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Abstract Background Infertility is a widespread problem for couples worldwide, and lifestyle factors are the cornerstone of infertility prevention. This research seeks to explore the association between combined healthy lifestyles and infertility risk among women of reproductive age. Methods This study analyzed data from the National Health and Nutrition Examination Survey (NHANES, 2013–2018), concentrating on 2,154 women aged 18 to 44. A healthy lifestyle score was created based on healthy diet (top two-fifths of the Healthy Eating Index-2015 score), low-to-moderate alcohol drinking (1–14 g/day), optimal waist circumference (less than 80 cm), adequate physical activity (at least 150 min of moderate-to-vigorous leisure-time exercise per week), and current nonsmoking. Weighted logistic regression analysis was applied to assess the link between healthy lifestyle scores and the risk of infertility, adjusting for potential confounders. Results After adjusting for potential confounders, women exhibiting 4 to 5 healthy lifestyle factors demonstrated a 59% decrease in the likelihood of infertility (OR: 0.41, 95% CI: 0.23–0.76) relative to those with 0 to 1 healthy lifestyle factors. Additionally, each increment in healthy lifestyle factors corresponded to a 21% decrease in infertility risk (OR: 0.79, 95% CI: 0.68–0.92). Analysis of subgroups indicated that the inverse association was more pronounced in females younger than 30. Additionally, optimal waist circumference is the foremost factor contributing to this inverse relationship. Conclusion Adhering to healthy lifestyles significantly lowers the likelihood of infertility among reproductive-aged women. Public health initiatives could consider enhancing access to healthy diets, physical activity, and resources to reduce alcohol consumption and smoking. Further research is required to clarify their relationship and the underlying mechanisms.

Vascular cambium is the continuation of meristem activity at the top of plants, which promotes lateral growth of plants. The vascular cambium evolved as an adaptation for secondary growth, initially in early seed plants, and became more refined in the evolution of gymnosperms and angiosperms. In angiosperms, it is crucial for plant growth and wood formation. The vascular cambium is regulated by a complex interplay of phytohormones, which are chemical messengers that coordinate various aspects of plant growth and development. This paper synthesizes the current knowledge on the regulatory effects of primary plant hormones and peptide signals on the development of the cambium in forest trees, and it outlines the current research status and future directions in this field. Understanding these regulatory mechanisms holds significant potential for enhancing our ability to manage and cultivate forest tree species in changing environmental conditions.

Hydraulic fracturing is a widely used technique for increasing the permeability of coal seams. Its impact on the production capacity of coalbed methane(CBM) wells is significant. This paper makes detailed observations on the exposed coal seams and fracture distribution of 5 CBM wells in Tunlan block of Xishan coalfield, and studies the distribution characteristics of coal structure, microfractures, quartz sand and coal fine by using stereoscopic microscope, scanning electron microscope, and micro CT. The fracturing effect and influencing factors of CBM wells are analysed by combining regional geostress and hydraulic fracturing construction parameters. The research results indicate that the macroscopic fractures morphology produced by hydraulic fracturing are complex and diverse, including horizontal, vertical, X and T-shaped fractures. The degree of coal body fragmentation increases with distance from the CBM well. The coal body closer to the CBM well is mainly composed of fragmented and granular coal, while the coal body further away is mainly composed of undeformed coal with primary fractures. The quartz sands are mainly deposited in horizontal fractures, with only a small amount in T-shaped fractures. Quartz sand rubs, collides, and embeds strongly with the coal fracture surface. The fracturing fluid is then superimposed to fracture the coal body, resulting in a large amount of coal fines. This causes the coal fines to wrap around the quartz sand and block the fractures. The coal fines within the macroscopic fracture are primarily a result of the fracturing of the coal body, the flushing of the coal body by fracturing fluid, and the friction between the quartz sand and the fracture surface during hydraulic fracturing. Coal fine generation in micro-fractures during coal body fracturing. Coal fines and quartz sand accumulate in the fractures, creating enormous resistance to the carrying fluid and preventing the quartz sand from migrating to the far end of the CBM well. The magnitude and direction of the geostress, as well as the strength of the coal seam roof and floor, are important factors that influence the opening and direction of the hydraulic fracturing fractures. The low viscosity of the carrying fluid cannot suspend quartz sand, and the accumulation of quartz sand and coal fine can block the fractures, easy to cause quartz sand and coal fine to aggregate and block fractures.

Datong Coalfield was intruded by igneous intrusions in both the Indosinian (Late Permian to the end of the Triassic) and the Yanshan (Late Jurassic to the Early Cretaceous) periods，which caused contact metamorphism of the coal seam. Previous studies have shown that Sr is significantly enriched in coal from the 5222 tunnel of the Tashan coal mine. The maximum concentration of Sr in thermally-altered and unaffected coal is 3067 μg/g and 2729 μg/g respectively, and the average concentration of Sr is 1165 μg/g, which is 10.6times of the world average level in hard coal. However, the modes of occurrence of Sr in the Tashan coal still remain unclear. Samples in the 5222 tunnel including coal and intrusive rock were systematically collected. Inductively coupled plasma mass spectrometry (ICP-MS) and X-ray fluorescence spectrometry (XRF) were applied to elucidate Sr concentration variations in the sample; correlation analysis, scanning electron microscope with energy spectrum (SEM-EDS), and sequential chemical extraction procedure (SCEP) were carried out to reveal the occurrence modes of Sr, as well as the characteristics of Sr-bearing minerals. The results demonstrated that Sr exhibits a strong correlation with P2O5 in coal; Sr mainly occurs in phosphate (apatite) and clay minerals that are intimately associated; apatite was distinguished as fluorapatite in the shape of hexagonal columns and hydroxyapatite in the shape of fine scattered particles embedded in the clay minerals.

In order to explore the fracturing characteristics of coalbed methane wells in the Tunlan block, the No.2 coal seam in the Tunlan block, Xishan, Taiyuan was taken as the research object. The fracturing characteristics of the coal seams from multiple scales was studied through geological cataloguing, macroscopic characterization of coal samples and CT (Computed Tomography) analysis for four coal bed methane wells of XST-167, XST-168, XST-176 and XST-177, which were exposed at the coal mining face. The results shown that, the coal seam near the wells in the study area were mainly distributed with “X” type fractured fractures consisting of diagonally intersecting fractures, and there were “T” type fractured fractures near the XST-177 coalbed methane well. Collision and friction of quartz sand with fractured fracture walls produced pulverized coal, which filled in the fracture and hindered the output of coalbed methane. By comparing the drill holes exposed by the two coalbed methane wells of XST-168 and XST-177, it was found that the fracturing effect of the XST-177 coalbed methane well was better and more conductive to the output of coalbed methane. Most of the coals near coalbed methane wells were fragmented and crushed coal, and hydraulic fracturing destroyed the original structure of coal, which reduced the hardness of coal and significantly increased the cracks. Embedded quartz sand can be observed on some of the coal samples, which was mainly concentrated on the bedding surface, indicating that the quartz sand, after being pressed into the coal seam, mainly extended into the seam along the horizontal fracture, which was consistent with the direction of the maximum principal stress. By CT scanning technology, the coal samples affected by fracturing (fractured coal) and not affected by fracturing (normal coal) were scanned. It was found that, the fractures with a width greater than 100 μm in the fractured coals of T1 and T2 accounted for 58.8% and 48.5% of the total fracture volume, and the numbers of the fractures was 23407 and 19679, respectively. In normal coal T3, the fractures with width greater than 100 μm only accounted for 1.7% of the total fracture volume, and the number of fractures was only 3504. The width of the fractures in T1 and T2 was wider and the number of fractures was more than that in T3, which indicated that the width and number of fractures in the coal sample were significantly increased by the fracturing action, and the pores and fractures in the fractured coal were more developed.

Delta-12 fatty acid desaturases (FAD2s) actively regulate stress responses and cell differentiation in living organisms. In this study, six homologous FAD2 genes were identified based on the genome sequence of Lentinula edodes. Then, the six FAD2 protein sequences were analyzed using bioinformatics tools, including ExPASy ProtParam, SignalP, TMHMM, and TargetP. These analyses were performed to predict the physical and chemical properties, signal peptides, and transmembrane and conserved domains of these proteins. The polypeptide sequences were aligned, and a maximum likelihood phylogenetic tree was constructed using MEGA 7.0 software to elucidate the phylogenetic relationships between homologous FAD2 sequences. The results demonstrated that the FAD2 proteins contained three conserved histidine-rich regions (HXXXH, HXXHH, and HXXHH), which included eight histidine residues. The linoleic acid content and FAD2 enzyme activity were further analyzed, and the levels in the mutagenic heat-tolerant strain 18N44 were lower than those in the wild-type strain 18. Interestingly, the expression levels of the FAD2-2 and FAD2-3 genes under heat stress in strain 18N44 were lower than those in strain 18. These findings indicated that FAD2-2 and FAD2-3 may play major roles in the synthesis of linoleic acid during heat stress.

Despite its low frequency, osteosarcoma is one of the deadliest malignancies in children and adolescents. The phosphatidylinositol 3-kinase (PI3K)/Akt signaling activation and epithelial-to-mesenchymal transition (EMT) are critical issues during osteosarcoma development. This study found long intergenic non-protein coding RNA 1060 (LINC01060) to be an EMT-related long non-coding RNA (lncRNA) up-regulated in osteosarcoma; higher LINC01060 expression was linked to a worse prognosis in osteosarcoma patients. In vitro, knocking down LINC01060 significantly inhibits osteosarcoma cell malignant behaviors, including hyperproliferation, invasion, migration, and EMT. In vivo, LINC01060 knockdown inhibited tumor growth and metastasis, and suppressed PI3K and Akt phosphorylation. In osteosarcoma cells, Akt agonist SC79 exerted opposite effects to those of LINC01060 knockdown through the promotion of cell viability, cell migration, and cell invasion. Moreover, the Akt agonist SC79 partially eliminated LINC01060 knockdown effects on osteosarcoma cells, suggesting that LINC01060 exerts its effects through the PI3K/Akt signaling. Therefore, it is deduced that LINC01060 is overexpressed in osteosarcoma. In vitro, LINC01060 knockdown inhibits cancer cell malignant behaviors; in vivo, LINC01060 knockdown inhibits tumor development and metastasis. The PI3K/Akt signaling is involved in LINC01060 functions in osteosarcoma.

Abstract With the development and progress of nanotechnology, the prospect of using nanorobots to achieve targeted drug delivery is becoming possible. Although nanorobots can potentially improve nano-drug delivery systems, there remains a significant challenge to fabricating magnetically controllable nanorobots with a size suitable for drug delivery in complex in vivo environments. Most of the current research focused on the preparation and functionalization of microscale and milliscale robots due to the relative difficulties in fabricating nanoscale robots. To address this problem and move towards in vivo applications, this study uses electron beam lithography to fabricate achiral planar L-shaped nanorobots that are biocompatible with immune cells. Their minimal planar geometry enabled nanolithography to fabricate nanorobots with a minimum feature size down to 400 nm. Using an integrated imaging and control system, the locomotive behavior of the L-shaped nanorobots in a fluidic environment was studied by examining their velocity profiles and trajectories. Furthermore, the nanorobots exhibit excellent cell compatibility with various types of cells, including macrophage cells. Finally, the long-term cell culture medium immersion test demonstrated that the L-shaped nanorobots have robust stability. This work will demonstrate the potential to use these nanorobots to operate in vivo without triggering immune cell responses.

Ultraviolet lithography is a very promising technology used for the batch fabrication of biomedical microswimmers. However, creating microswimmers that can swim at low Reynolds number using biocompatible materials while retaining strong magnetic properties and excellent biomedical functionality is a great challenge. Most of the previously reported biomedical microswimmers possess either strong magnetic properties by using non-biocompatible nickel coating or good biocompatibility by using iron oxide particle-embedded hydrogel with weak magnetism, but not both. Alternatively, iron oxide nanoparticles can be coated on the surface of microswimmers to improve magnetic properties; however, this method limited the usability of the microswimmers’ surfaces. To address these shortcomings, this work utilized an in situ synthesis technique to generate high magnetic content inside hydrogel-based achiral planar microswimmers while leaving their surfaces free to be functionalized for SERS detection. The hydrogel matrices of the magnetically actuated hydrogel-based microswimmers were first prepared by ultraviolet lithography. Then, the high concentration of iron oxide was achieved through multiple continuous in situ coprecipitation cycles. Finally, the SERS detection capability of magnetically actuated hydrogel-based microswimmers was enabled by uniformly growing silver nanoparticles on the surface of the microswimmers. In the motion control tests, the microswimmers showed a high swimming efficiency, high step-out frequency, and consistent synchronized motion. Furthermore, the magnetically actuated hydrogel-based microswimmers were able to improve the detection efficiency of analytes under magnetic guidance.

Abstract Magnetic micro/nanorobots attracted much attention in biomedical fields because of their precise movement, manipulation, and targeting abilities. However, there is a lack of research on intelligent micro/nanorobots with stimuli-responsive drug delivery mechanisms for cancer therapy. To address this issue, we developed a type of strong covalently bound tri-bead drug delivery microrobots with NIR photothermal response azobenzene molecules attached to their carboxylic surface groups. The tri-bead microrobots are magnetic and showed good cytocompatibility even when their concentration is up to 200 µg/mL. In vitro photothermal experiments demonstrated fast NIR-responsive photothermal property; the microrobots were heated to 50 °C in 4 min, which triggered a significant increase in drug release. Motion control of the microrobots inside a microchannel demonstrated the feasibility of targeted therapy on tumor cells. Finally, experiments with lung cancer cells demonstrated the effectiveness of targeted chemo-photothermal therapy and were validated by cell viability assays. These results indicated that tri-bead microrobots have excellent potential for targeted chemo-photothermal therapy for lung cancer cell treatment.

Summary: To realize the potential to use micro/nanorobots for targeted cancer therapy, it is important to improve their biocompatibility and targeting ability. Here, we report on drug-loaded magnetic microrobots capable of polarizing macrophages into the antitumor phenotype to target and inhibit cancer cells. In vitro tests demonstrated that the microrobots have good biocompatibility with normal cells and immune cells. Positively charged DOX was loaded onto the surface of microrobots via electrostatic interactions and exhibited pH-responsive release behavior. The nano-smooth surfaces of the microrobots activated M1 polarization of macrophages, thus activating their intrinsic targeting and antitumor abilities toward cancer cells. Through dual targeting from magnetic guidance and M1 macrophages, the microrobots were able to target and kill cancer cells in a 3D tumor spheroid culture assay. These findings demonstrate a way to improve the tumor-targeting and antitumor abilities of microrobots through the combined use of magnetic control, macrophages, and pH-responsive drug release.

2-Deoxy-D-glucose (2-DG) is a glucose analog used as a promising anticancer agent. It exerts its effects by inhibiting the glycolytic energy metabolism to deplete cells of energy. The larval stage of Echinococcus relies on glycolysis for energy production. Therefore, in this study, we investigated the in vitro and in vivo efficacy of 2-DG against the larval stage of Echinococcus granulosus and E. multilocularis. 2-DG exhibited significant time- and dose-dependent effects against in vitro cultured E. granulosus protoscoleces and E. multilocularis metacestodes. A daily oral administration of 500 mg/kg 2-DG in E. multilocularis-infected mice effectively reduced the weight of metacestodes. Notably, the combination treatment, either 2-DG (500 mg/kg/day) + albendazole (ABZ) (200 mg/kg/day) or 2-DG (500 mg/kg/day) + half-dose of ABZ (100 mg/kg/day), exhibited a potent therapeutic effect against E. multilocularis, significantly promoting the reduction of metacestodes weight compared with the administration of 2-DG or ABZ alone. Furthermore, the combination significantly promoted apoptosis of the cells of metacestodes and inhibited glycolysis in metacestodes, compared with the administration of 2-DG or ABZ alone. In conclusion, 2-DG exerts an effective activity against the larval stage of Echinococcus. Thus, it may be a promising anti-Echinococcus drug, and its combination with ABZ may provide a new strategy for the treatment of echinococcosis in humans.

Abstract Background Cystic echinococcosis (CE), caused by the larval stage of Echinococcus granulosus (sensu stricto), is a life-threatening but neglected zoonosis. Glycolytic enzymes are crucial molecules for the survival and development of E. granulosus. The aim of this study was to investigate the molecular characterization, immunogenicity, tissue distribution and serodiagnostic potential of E. granulosus hexokinase (EgHK), the first key enzyme in the glycolytic pathway. Methods EgHK was cloned and expressed in Escherichia coli. Specific serum antibodies were evaluated in mice immunized with recombinant EgHK (rEgHK). The location of EgHK in the larval stage of E. granulosus was determined using fluorescence immunohistochemistry, and the potential of rEgHK as a diagnostic antigen was investigated in patients with CE using indirect enzyme-linked immunosorbent assay (ELISA). Results Recombinant EgHK could be identified in the sera of patients with CE and in mouse anti-rEgHK sera. High titers of specific immunoglobulin G were induced in mice after immunization with rEgHK. EgHK was mainly located in the tegument, suckers and hooklets of protoscoleces and in the germinal layer and laminated layer of the cyst wall. The sensitivity and specificity of the rEgHK-ELISA reached 91.3% (42/46) and 87.8% (43/49), respectively. Conclusions We have characterized the sequence, structure and location of EgHK and investigated the immunoreactivity, immunogenicity and serodiagnostic potential of rEgHK. Our results suggest that EgHK may be a promising candidate for the development of vaccines against E. granulosus and an effective antigen for the diagnosis of human CE.

Multi-domain knowledge organization is an effective way of correlating cross-domain knowledge or intercommunicating between cross-domain knowledge systems. As a knowledge organization model, ontology is widely used in information and management systems. To organize multi-domain knowledge, ontologies in different domains correlate to each other directly or indirectly. Generally, matching and integrating ontologies of different domain into a large scale ontology is the common way of directly correlating, while building a top level ontology is the main method for indirectly correlating. As the scale of domain ontologies get larger and larger, both direct and indirect methods become more difficult and time-consuming. In order to improve the organization of multi-domain knowledge, this paper presents a novel ontology organization method to build real-time ontology by adaptive filter while user presenting requirements. Only the entities related to user requirements are integrated, while building a real-time ontology. Firstly, the method searches domain ontologies that are related to user requirements. Then sub-ontologies are extracted from search results by filter, and they are integrated into a new ontology under direction of filter, i.e. real-time ontology. Finally, four criteria are introduced to evaluate real-time ontology. The experiment results illuminate that real-time ontology perform excellently in accuracy, recall, correctness and especially time-consuming.

ObjectiveTo prepare technetium-99m (99mTc)-labeled pH (low) insertion peptide variant 7 [pHLIP (Var7)] and carry out small-animal single-photon-emission computed tomography (SPECT)/computed tomography (CT) imaging of tumor-bearing nude mice in vivo to study its value in the early diagnosis of triple-negative breast cancer (TNBC).MethodsThe pHLIP (Var7) sequence was synthesized via solid-phase peptide synthesis. Four amino acids, Gly-(D)-Ala-Gly-Gly, were attached to the N-terminus of pHLIP (Var7) to form a strong chelating group containing an N4 structure. The peptide was labeled with 99mTc using a direct labeling method. We determined the in vitro binding fraction of 99mTc-pHLIP (Var7) to MDA-MB-231 cells. Serial biodistribution studies and small-animal SPECT/CT imaging in MDA-MB-231 TNBC-bearing mice were performed using 99mTc-pHLIP (Var7).ResultsThe radiochemical yield and purity of 99mTc-pHLIP (Var7) were 99.49 ± 0.17% and 99.63 ± 0.44%, respectively. The radiochemical purity was still more than 96% after 24 h in serum. The binding fraction of 99mTc-pHLIP (Var7) to MDA-MB-231 cells continuously increased in an acidic environment and was significantly higher than the cell-binding fraction (P < 0.01) at pH = 7.4 and the cell-binding fraction (P < 0.01) of 99mTc-kVar7 at different pH values (pH = 6.0, 6.5, 7.0 and 7.4) at each time point (P < 0.01). The distribution of 99mTc-pHLIP (Var7) in tumors at each time point was significantly greater than that of 99mTc-kVar7 (P < 0.01). SPECT/CT imaging was largely consistent with the biodistribution results; the tumor was clearly imaged at each time point after injection of 99mTc-pHLIP (Var7) but could not be imaged after injection of 99mTc-kVar7.Conclusion99mTc-pHLIP (Var7) showed a high radiochemical yield and stability and was highly concentrated in tumor tissues. Although there was strong radioactive background in the abdomen of tumor-bearing nude mice, it did not hinder early diagnosis of TNBC.

Background: Formaldehyde (FA) is ubiquitous in the environment and can be transferred to the fetus through placental circulation, causing miscarriage and congenital heart disease (CHD). Studies have shown that βII spectrin is necessary for cardiomyocyte survival and differentiation, and its loss leads to heart development defects and cardiomyocyte apoptosis. Additionally, previous studies have demonstrated that miRNA is essential in heart development and remodeling. However, whether miRNA regulates FA-induced CHD and cardiomyocyte apoptosis remains unclear.Methods: Using commercially available rat embryonic cardiomyocytes and a rat model of fetal cardiomyocyte apoptosis. Real-time quantitative PCR (RT-qPCR) and Western blot were performed to examine the level of miR-153-3p, βII spectrin, caspase 7, cleaved caspase7, Bax, Bcl-2 expression in embryonic cardiomyocytes and a rat model of fetal cardiomyocyte apoptosis. Apoptotic cell populations were evaluated by flow cytometry and Tunel. Luciferase activity assay and RNA pull-down assay were used to detect the interaction between miR-153-3p and βII spectrin. Masson's trichrome staining detects the degree of tissue fibrosis. Fluorescence in situ hybridization (FISH) and Immunohistochemistry were used to detect the expression of miR-153-3p and βII spectrin in tissues.Results: Using commercially available rat embryonic cardiomyocytes and a rat model of fetal cardiomyocyte apoptosis, our studies indicate that miR-153-3p plays a regulatory role by directly targeting βII spectrin to promote cardiomyocyte apoptosis. miR-153-3p mainly regulates cardiomyocyte apoptosis by regulating the expression of caspase7, further elucidating the importance of apoptosis in heart development. Finally, the results with our animal model revealed that targeting the miR-153-3p/βII spectrin pathway effectively regulated FA-induced damage during heart development. Recovery experiments with miR-153-3p antagomir resulted in the reversal of FA-induced cardiomyocyte apoptosis and fetal cardiac fibrosis.Conclusion: This study investigated the molecular mechanism underpinning the role of βII spectrin in FA-induced CHD and the associated upstream miRNA pathway. The study findings suggest that miR-153-3p may provide a potential target for the clinical diagnosis and treatment of CHD.

Coal maceral composition has a great effect on gas adsorption and diffusion. The interaction between maceral composition and supercritical CO2 (SCCO2) fluid will affect gas diffusion behavior in coals. Thus, the diffusivity derived from adsorption kinetics of CH4 and CO2 in vitrinite- and inertinite-rich coals with low-violate bituminous rank collected from the Hancheng mine of the Weibei coalfield pre- and post-SCCO2 fluid exposure (SFE) were tested at the conditions of 45 °C and 0.9 MPa. In combination with pore distribution and functional group content, the possible mechanism of the alterations in gas diffusion characteristics in coals with various maceral compositions was addressed. The results show that for vitrinite-rich coals, SFE increases the macropore apparent diffusion coefficient of CH4, while this treatment decreases the micropore apparent diffusion coefficient of CH4. However, the reverse trend is found for CO2 diffusion–adsorption rate. For inertinite-rich coals post-SFE, CH4 diffusion–adsorption rate increases, while an increase and a decrease in diffusivity CO2 occur for macropore and micropore, respectively. Generally, SFE shows a stronger impact on CO2 adsorption rate than CH4 in coals. The results suggest that the diffusion of CH4 and CO2 in coals with different maceral compositions show selectivity to SCCO2 fluid. The possible reason can be attributed to the changes in pore structure and surface functional group content. SFE causes an increase in macro/mesopore volume of all samples. However, SFE induces a reduction in oxygen-containing species content and micropore volume of inertinite-rich coals, while the opposite trend occurs in vitrinite-rich coals. Thus, the changes in pore volume and surface functional group account for the difference in gas diffusivity of coals with different maceral compositions. With regard to the micropore diffusion–adsorption behavior of CH4 and CO2, the impact of oxygen-containing species is superior to pore volume. The oxygen-containing species favor CO2 diffusion–adsorption but go against CH4 transport. This effect accounts for the reduction in the micropore diffusion–adsorption rate of CH4 and the increase in micropore diffusivity of CO2 in vitrinite-rich coals, respectively. However, the aforementioned effect is the opposite for inertinite-rich coals. Overall, the changes in gas diffusion in coals with different maceral composition during the CO2-ECBM process requires further attention.

Abstract Echinococcosis is a zoonotic disease caused by cestode species of the genus Echinococcus, which demonstrates considerable medical and veterinary concerns. The development of novel drugs for echinococcosis treatment is urgently needed. In this study, we demonstrated that lonidamine (LND) and 6-aminonicotinamide (6-AN) exhibited considerable in vitro effects against both larval- and adult-stage of E. granulosus sensu stricto (s. s.) and E. multilocularis. The combination of LND and 6-AN exhibited a significantly higher activity than the single drug treatment. These results highlight the therapeutic potential of LND, 6-AN and the combination of LND and 6-AN for the treatment of echinococcosis.

Abstract While searching for novel anti-echinococcosis drugs, we have been focusing on glycolysis which is relied on by Echinococcus for energy production and intermediates for other metabolic processes. The aim of this study was to investigate the potential therapeutic implication of glycolytic inhibitors on Echinococcus. Our results demonstrate that at an initial concentration of 40 μM, all inhibitors of glycolysis used in the current experiment [3-bromopyruvate (3-BrPA), ornidazole, clorsulon (CLS), sodium oxamate and 2,6-dihydroxynaphthalene (NA-P2)] show considerable in vitro effects against Echinococcus granulosus protoscoleces and Echinococcus multilocularis metacestodes. Among them, 3-BrPA exhibited the highest activity which was similar to that of nitazoxanide (NTZ) and more efficacious than albendazole (ABZ). The activity of 3-BrPA was dose dependent and resulted in severe ultrastructural destructions, as visualized by electron microscopy. An additional in vivo study in mice infected with E. multilocularis metacestodes indicates a reduction in parasite weight after the twice-weekly treatment of 25 mg/kg 3-BrPA for 6 weeks, compared to that of the untreated control. In particular, in contrast to ABZ, the administration of 25 mg/kg 3-BrPA did not cause toxicity to the liver and kidney in mice. Similarly, at the effective dose against Echinococcus larvae, 3-BrPA showed no significant toxicity to human hepatocytes. Taken together, the results suggest that interfering with the glycolysis of the parasite may be a novel chemotherapeutical option and 3-BrPA, which exhibited a remarkable activity against Echinococcus, may be a promising potential drug against cystic echinococcosis (CE) and alveolar echinococcosis (AE).

In this paper, a multi-strategy adaptive comprehensive learning particle swarm optimization algorithm is proposed by introducing the comprehensive learning, multi-population parallel, and parameter adaptation. In the proposed algorithm, a multi-population parallel strategy is designed to improve population diversity and accelerate convergence. The population particle exchange and mutation are realized to ensure information sharing among the particles. Then, the global optimal value is added to velocity update to design a new velocity update strategy for improving the local search ability. The comprehensive learning strategy is employed to construct learning samples, so as to effectively promote the information exchange and avoid falling into local extrema. By linearly changing the learning factors, a new factor adjustment strategy is developed to enhance the global search ability, and a new adaptive inertia weight-adjustment strategy based on an S-shaped decreasing function is developed to balance the search ability. Finally, some benchmark functions and the parameter optimization of photovoltaics are selected. The proposed algorithm obtains the best performance on 6 out of 10 functions. The results show that the proposed algorithm has greatly improved diversity, solution accuracy, and search ability compared with some variants of particle swarm optimization and other algorithms. It provides a more effective parameter combination for the complex engineering problem of photovoltaics, so as to improve the energy conversion efficiency.

Background: The COVID-19 pandemic is a major public health issue and challenge to health professionals. In similar epidemics, nurses experienced more distress than other providers.Methods: We surveyed both on-duty nurses caring for infected patients and second-line nurses caring for uninfected patients from Hubei and other provinces throughout China.Results: We received completed surveys from 1,364 nurses from 22 provinces: 658 front-line and 706 second-line nurses. The median (IQR) GHQ-28 score of all nurses was 17 (IQR 11–24). The overall incidence of mild-to-moderate distress (GHQ score > 5) was 28%; that for severe distress (GHQ score > 11) was 6%. The incidence of mild-to-moderate distress in the second-line nurses was higher than that in the front-line nurses (31 vs. 25%; OR, 0.74; 95 CI, 0.58–0.94). Living alone (OR, 0.62; 95% CI, 0.44–0.86) and feeling supported (OR, 0.82, 95% CI, 0.74–0.90) independently predicted lower anxiety.Conclusions: During the COVID-19 pandemic, the psychological problems of all nurses were generally serious. The interviewed second-line nurses face more serious issues than the front-line nurses.

Low temperature can lead to the autolysis of Volvariella volvacea (V. volvacea), hindering its growth and preservation and severely reducing its yield and quality. This autolysis of V. volvacea at low temperature has been reported, but a metabolomics-based investigation of the underlying mechanisms of the V. volvacea response to low temperature has not been reported. Therefore, this study aimed to explore the changes, levels and expression patterns of V. volvacea metabolites at low temperature. To understand the metabolic differences within V. volvacea, two strains with different levels of low-temperature tolerance were treated in an ice bath at 0°C for 2, 4, 8, and 10 h, while the blank control group was treated for 0 h. Metabonomics analysis was adopted to study the changes in V. volvacea in response to low temperature and the differences between the two different strains. Metabolic curves were analyzed at different time points by high-performance liquid chromatography-mass spectrometry (HPLC-MS). A total of 216 differential metabolites were identified and enriched in 39 metabolic pathways, mainly involving amino acid metabolism, carbohydrate metabolism, the TCA cycle, energy metabolism, etc. In this paper, we report the metabonomic analysis of V. volvacea in response to low temperature and compare the differences in metabolite expression between the low-temperature-resistant strain VH3 and the low-temperature-sensitive strain V23. Finally, the putative low-temperature resistance mechanism of VH3 is revealed at the metabolic level. This study provides a theoretical basis for revealing the regulatory mechanism of low-temperature resistance in V. volvacea and for future molecular breeding efforts.

Abstract Echinococcosis is a zoonotic infection caused by cestode species of the genus Echinococcus, with limited treatment options. It is urgent to develop new anti-hydatid agent. In this paper, we reported anacardic acid (AA), a natural product isolated from the Brazilian cashew-nut shell liquid, which presented a high activity against metacestodes of Echinococcus multilocularis (E. multilocularis) and Echinococcus granulosus sensu stricto (E. granulosus s.s.) in vitro and in vivo. AA exerted a better efficacy on E. granulosus s.s. protoscoleces and E. multilocularis metacestodes than that of albendazole (ABZ) and dihydroartemisinin (DHA) in vitro, and an inhibition on the growth of Echinococcus metacestode as effective as ABZ in vivo. Moreover, we also found that one of the mechanisms of AA against Echinococcus could be the suppression of angiogenesis on/in the metacestode mass through inhibiting vascular endothelial growth factor (VEGF)—induced signalling pathways. This work finds that AA is a new promising potential candidate drug for echinococcosis treatment.

In this study, changes in metabolites during the fermentation of Agaricus bisporus compost under the Shanghai Lianzhong secondary fermentation method and Jiangsu Yuguan tertiary fermentation method were analysed by applying gas chromatography–mass spectrometry (GC–MS) to understand the differences in metabolites under different fermentation methods and find metabolic markers at different fermentation stages in different fermentation methods. The results showed that 1002 compounds were identified. Based on the differential metabolites from pathways of significant enrichment, it was found that L-aspartic acid and 5-aminobenzolevulinic acid could be used as potential metabolic markers to evaluate the phase 2 fermentation method of Shanghai Lianzhong and the phase 3 fermentation method of Jiangsu Yuguan, respectively. This study provides a reference for the preparation of quality-stable fermentation materials and further understanding of the cultivation of A. bisporus with fermentation materials.

The small size of robotic microswimmers makes them suitable for performing biomedical tasks in tiny, enclosed spaces. Considering the effects of potentially long-term retention of microswimmers in biological tissues and the environment, the degradability of microswimmers has become one of the pressing issues in this field. While degradable hydrogel was successfully used to prepare microswimmers in previous reports, most hydrogel microswimmers could only be fabricated using two-photon polymerization (TPP) due to their 3D structures, resulting in costly robotic microswimmers solution. This limits the potential of hydrogel microswimmers to be used in applications where a large number of microswimmers are needed. Here, we proposed a new type of preparation method for degradable hydrogel achiral crescent microswimmers using a custom-built stop-flow lithography (SFL) setup. The degradability of the hydrogel crescent microswimmers was quantitatively analyzed, and the degradation rate in sodium hydroxide solution (NaOH) of different concentrations was investigated. Cytotoxicity assays showed the hydrogel crescent microswimmers had good biocompatibility. The hydrogel crescent microswimmers were magnetically actuated using a 3D Helmholtz coil system and were able to obtain a swimming efficiency on par with previously reported microswimmers. The results herein demonstrated the potential for the degradable hydrogel achiral microswimmers to become a candidate for microscale applications.

Carboniferous–Permian coal seams in the Datong coalfield are intruded by Mesozoic magmatic dikes and sills. Our observations indicate that these dikes and sills have been seriously altered and have lost their original characteristics. Although this phenomenon has been mentioned in some studies, there is a lack of detailed research on the alteration mechanism. To fill this research gap, six dike samples were collected in this study to analyze their alteration characteristics and mechanisms. Petrographic analysis, scanning electron microscopy, and X-ray diffraction were used to determine the mineralogy of the altered igneous samples. The results suggest that the mineral alteration is associated with severe carbonation and clavization. The carbonation of mafic minerals is due to the release of CO2 generated from the coking of high volatile bituminous coals that may have occurred during the intrusive event. However, labradorite did not react with CO2. The water activity in the coal seam was enhanced by the dikes, and mafic minerals were converted into mixtures of chlorite and smectite group minerals. The water activity is especially high at the edges of the dike. Albite and clay minerals were formed due to the albitization of labradorite. Based on these effects, the dike can be divided into weak alteration, carbonation, and clavization bands. The alteration processes in the coal seam are described in detail in this work, and potential formation mechanisms are suggested.

Context: Previous studies have reported that caveolin-1 (Cav-1) is associated with lung fibrosis. However, the role of Cav-1 expression in pirfenidone-treated idiopathic pulmonary fibrosis (IPF) is unknown. Objective: This study investigated Cav-1 expression in pirfenidone-treated IPF, and compared the effects of pirfenidone with acetylcysteine and prednisone on IPF. Materials and methods: Rat IPF model was established by endotracheal injection of 5 mg/kg bleomycin A5 into the specific pathogen-free Wistar male rats. Pirfenidone (P, 100 mg/kg once daily), prednisone (H, 5 mg/kg once daily) and acetylcysteine (N, 4 mg/kg 3 times per day) were used to treat the rat model by intragastric administration for 45 consecutive days, respectively. The normal rats without IPF were used as the controls. After 15, 30 and 45 days of drug treatment, lung histopathology was assessed. The expression of Cav-1 was determined using real-time quantitative PCR and Western blot; the expression of tumour necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1) and platelet-derived growth factor (PDGF) was determined by enzyme-linked immunosorbent assay. Results: After 15, 30 and 45 days of drug treatment, comparison of the three drug-treated groups with the model group showed significantly lower (p

Bone homeostasis and resorption is regulated by the proper activation of osteoclasts, whose stimulation largely depends on the receptor activator of nuclear factor κB ligand (RANKL)-RANK signaling. Herein, for the first time, we showed that interferon regulatory factor (Irf)-3 was intimately involved in RANKL-induced osteoclast formation. In addition, hesperetin (Hes) derived from citrus fruit could inhibit RANKL-induced osteoclast differentiation and maturation among three types of osteoclast precursors with inhibited formation of F-actin rings and resorption pits on bone slices. More importantly, by using SP600125, a selective Jnk inhibitor, we showed that Hes was able to significantly attenuate the Jnk downstream expression of Irf-3 and c-Jun, thereby inactivating NF-κB/MAPK signaling and transcriptional factor NFATc-1, leading to suppression of osteoclast-specific genes, which resulted in impaired osteoclastogenesis and functionality. An ovariectomized (OVX) osteoporosis mouse model demonstrated that Hes could increase trabecular bone volume fractions (BV/TV), trabecular thickness, and trabecular number, whereas it decreased trabecular separation in OVX mice with well-preserved trabecular bone architecture and decreased levels of TRAP-positive osteoclasts. This is further evidenced by the diminished serum expression of bone resorption marker CTX and enhanced production of osteoblastic ALP in vivo. Taken together, these results suggested that Hes could inhibit Jnk-mediated Irf-3/c-Jun activation, thus attenuating RANKL-induced osteoclast formation and function both in vitro and in vivo.

Mechanical damage can induce fruiting body production in fungi. In this study, the antioxidant kojic acid (KA) was found to enhance injured mycelial regeneration and increase fruiting body production in Hypsizygus marmoreus. KA reduced the level of reactive oxygen species (ROS), which are harmful to mycelia when excessively generated by mechanical damage. Moreover, KA increased catalase and superoxide dismutase activities and glutathione and ascorbic acid contents by up-regulating antioxidant gene expression. These results suggest that KA promotes mycelial regeneration in response to damage by activating a "stress signal" and enhances the ability of H. marmoreus to resist oxidative damage by invoking the antioxidant system. In addition, KA increased the content of extracellular ATP, which serves as a "stress signal" in response to injury, and modulated ROS signaling, decreasing NADPH oxidase gene expression and ROS levels in the mycelial-regeneration stage. KA treatment also up-regulated the MAPK, Ca2+ and oxylipin pathways, suggesting their involvement in the damage response. Furthermore, laccase and cellulase activities were stimulated by KA at different developmental stages. These results demonstrate that KA regulates gene expression and activates pathways for mycelial wound healing, regeneration of damaged mycelia and reproductive structure formation in the basidiomycete H. marmoreus.

The complete mitochondrial genome of the widely cultivated edible fungus Lentinula edodes was determined using the next-generation sequencing technology. The circular molecule is 116,819 bp in length with a GC content of 30.75%. Conserved genes including 13 putative protein-coding genes and 24 tRNAs were located on the same strand. We detected 14 introns invading 4 genes, including cob, cox1, nad1, and nad5. The phylogenetic analysis confirmed that L. edodes was a number of Agaricales. This mitochondrial genome may open new avenues for understanding the phylogeny and evolution of Omphalotaceae and Agaricales.