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Abstract Oxidative stress (OS) and neuroinflammation are critical pathological processes in secondary brain injury (SBI) after intracerebral hemorrhage(ICH), and their intimate interactions initiate and aggravate brain damage. Thus, targeting oxidative stress and neuroinflammation could be a promising therapeutic strategy for ICH treatment. Here, we report a high-performance platform using polydopamine (PDA)-coated diselenide bridged mesoporous silica nanoparticle (PDA-DSeMSN) as a smart ROS scavenger and ROS-responsive drug delivery system. Caffeic acid phenethyl ester (CAPE) was blocked in the pore of DSeMSN by covering the pore with PDA as a gatekeeper. PDA-DSeMSN @CAPE maintained high stability and underwent reactive oxygen species (ROS)-responsive degradation and drug release. The intelligent nanomaterial effectively eliminated ROS, promoted M1 to M2 microglial conversion and suppressed neuroinflammation in vitro and in vivo. Importantly, intravenous administration of PDA-DSeMSN@CAPE specifically accumulated in perihematomal sites and demonstrated robust neuroprotection in an ICH mouse model with high biological safety. Taking together, the synergistic effect of ROS-responsive drug delivery ability and ROS scavenging ability of PDA-DSeMSN makes it a powerful drug delivery platform and provided new considerations into the therapeutic action to improve ICH-induce brain injury. Graphical Abstract

Abstract This article proposes a novel compact wideband dielectric resonator antenna design that incorporates inhomogeneous material distribution in a cubic structure. Specifically, in this design, the cubic dielectric resonator antenna is divided into multiple small blocks, and a continuous genetic algorithm is employed to optimize the material property of each block in order to maximize the radiation bandwidth. As a result, a cubic dielectric resonator antenna with inhomogeneous material distributions is designed and tested. In measurement, the proposed compact dielectric resonator antenna design exhibits 64.9% impedance bandwidth (4.08–8 GHz), considerably higher than the bandwidth of the initial homogeneous dielectric resonator antenna. The maximum system gain achieved over the frequency range is 9 dB at 7 GHz, with a peak measured system efficiency of 90.6%.

BackgroundLung adenocarcinoma patients are often found to have developed bone metastases at the time of initial diagnosis. With the continuous development of technology, we have successfully entered the era of immunotherapy. This study aimed to determine the efficacy of immunotherapy in lung adenocarcinoma patients with bone metastases (LABM) through a multicenter retrospective analysis and to develop a novel tool to identify the population that could benefit most from immunotherapy.MethodsTo assess the impact of immunotherapy on LABM in terms of overall survival, we used analytical tools such as Kaplan-Meier analysis, Log-ranch test, and propensity score matching (PSM) method. A predictive model for constructing overall survival was constructed using Cox regression modeling. Based on this, we developed a risk classification system depicting Kaplan-Meier curves for subgroup analysis to determine the optimal beneficiary population for immunotherapy in different risk subgroups.ResultsA total of 20073 eligible patients were enrolled in this study, of whom 8010 did not receive immunotherapy, while 12063 patients received immunotherapy. After 1:1 PSM, 15848 patients were successfully coordinated, yielding a balanced cohort. Kaplan-Meier survival curves showed significantly enhanced overall survival (P < 0.001) in patients who received immunotherapy compared to those who did not. The results of Cox regression analyses showed that age, race, sex, primary site, immunotherapy, surgery, chemotherapy, brain metastasis, liver metastasis, lung metastasis, and marital status were independent prognostic factors. The area under the curve for all three cohorts was close to 0.7, indicating that the model was well-discriminating. The calibration curves further proved that the model had a high predictive accuracy. Decision curve analysis demonstrated that the model could achieve a high net clinical benefit. The risk classification system developed based on the model successfully screened the best beneficiary population for immunotherapy.ConclusionThis study provides convincing evidence that immunotherapy provides a significant survival advantage for LABM. Secondly, the clinical tools constructed in this study can help clinicians identify the optimal population to benefit from immunotherapy in LABM, thus enabling precise treatment and avoiding the waste of medical resources and over-treatment of patients.

Abstract Underground coal seam mining significantly alters the stress and energy distribution within the overlying rock, leading to eventual structural degradation. Therefore, it is imperative to quantitatively identify the temporal and spatial characteristics of stress evolution of overlying rock caused by mining. This paper introduces a novel rock stress model integrating entropy and a spatial–temporal cube. Similar material model tests are used to identify the abrupt entropy changes within the mining rock, and the trend analysis is carried out to describe the spatial–temporal evolution law of stress during mining. Experimental findings indicate elevated stress levels in the unmined rock preceding and following the panel, as well as within specific rock strata above it. Definitively, dynamic stress arches within the surrounding rock of the stope predominantly bear and distribute the load and pressure from the overlying rock, and each stress mutation is accompanied by a sudden stress entropy change. Over time, z-score shows that the noticeable reduction in mining-induced overburden stress becomes increasingly pronounced, especially in the water-conducting fracture zone. The model's bifurcation set serves as the comprehensive criterion for the entropy-induced sudden changes in the rock system, signifying overall failure.

Climate change cause extreme weather effects with temperature increases and drops in humidity, such as drought and heatwaves, which will lead to more evaporation in arid and semi-arid lands. The application of biochar made from crop straw without burning to farmland can effectively improve the water retention capacity of soil. A testing program has been carried out in a climate simulation laboratory to study the effects of different straw biochars on the cracking and evaporation of soils due to drying. Biochar from wheat straw (WS), corn straw (CS) and rice straw (RS) is produced at a pyrolysis temperature of 500℃. Thermogravimetric analysis and elemental analysis are carried out to obtain the properties of the biochar. Five percent of WS, CS and RS biochar by weight is added to acidic soil. Digital camera and digital image processing technology are used to analyze the crack morphology of the samples during evaporation. The results indicate that the RS biochar has the highest ash content (32.5 %), CS biochar has the highest content of volatile solid (25.36 %) and WS biochar has the highest content of fixed carbon (55.38 %). Biochar can effectively improve the water retention capacity of soil. The final water contents of the WS, CS and RS biochar soil samples are 132.3 %, 101.0 %, and 20.7 % respectively higher than that of the soil without biochar. Moreover, biochar can effectively reduce the degree of soil cracking. The addition of WS, CS and RS biochar can reduce soil cracking by 9.21 %, 16.57 %, and 7.46 %, respectively. WS contains more total cellulose than CS and RS, so WS biochar is the best choice to improve soil water retention ability. Therefore, biochar technology helps to optimize soil water retention while avoiding environmental pollution from straw burning.

With the rapid global spread of COVID-19 and the continuous emergence of variants, there is an urgent need to develop safe and effective vaccines. Here, we developed a novel mRNA vaccine, HC009, based on new formulation by the QTsome delivery platform. Immunogenicity results showed that the prime-boost immunization strategy with HC009 was able to induce robust and durable humoral immunity, as well as Th1-biased cellular responses in rodents or non-human primates (NHPs). After further challenge with live SARS-CoV-2 virus, HC009 provided adequate protection against virus infection in hACE2 transgenic mice. Therefore, HC009 could provide significant immune protection against SARS-CoV-2.

Abstract Background Blood brain barrier (BBB) breakdown is one of the key mechanisms of secondary brain injury following intracerebral hemorrhage (ICH). Astrocytes interact with endothelial and regulate BBB integrity via paracrine signaling factors. More and more studies reveal astrocyte-derived extracellular vesicles (ADEVs) as an important way of intercellular communication. However, the role of ADEV in BBB integrity after ICH remains unclear. Methods ADEVs were obtained from astrocytes with or without oxygen and glucose deprivation (OGD) pre-stimulation and the role of ADEVs in ICH was investigated using ICH mice model and ICH cell model. The potential regulatory effect of ADEVs on endothelial barrier integrity was identified by TEER, western blot and immunofluorescence in vitro. In vivo, functional evaluation, Evans-blue leakage and tight junction proteins (TJPs) expression were analyzed. MiRNA sequencing revealed that microRNA-27a-3p (miR-27a-3p) was differentially expressed miRNA in the EVs from OGD-pretreated astrocytes compared with normal control. The regulatory mechanism of miR-27a-3p was assessed using Luciferase assay, RT-PCR, western blot and immunofluorescence. Results OGD-activated astrocytes reduced hemin-induced endothelial hyper-permeability through secreting EVs. OGD-activated ADEVs alleviated BBB dysfunction after ICH in vivo and in vitro. MicroRNA microarray analysis indicated that miR-27a-3p is a major component that was highly expressed miRNA in OGD pretreated-ADEVs. OGD-ADEVs mitigated BBB injury through transferring miR-27a-3p into bEnd.3 cells and regulating ARHGAP25/Wnt/β-catenin pathway. Conclusion Taken together, these findings firstly revealed that miR-27a-3p, as one of the main components of OGD-pretreated ADEVs, attenuated BBB destruction and improved neurological deficits following ICH by regulating endothelial ARHGAP25/Wnt/β-catenin axis. OGD-ADEVs might be a novel strategy for the treatment of ICH. this study implicates that EVs from OGD pre-stimulated astrocytes. Graphical Abstract

To improve vehicle performance and energy utilization, a novel planetary gear set based flywheel hybrid electric powertrain (PGS-FHEP) is proposed. The PGS-FHEP involves an internal combustion engine, a planetary gear set that integrated a control motor and an energy storage flywheel, which combines the high efficiency of the mechanical flywheel energy storage system with the flexible and controllable characteristics of the electric motor. The powertrain is analyzed and modeled using lever analogy method, and a rule-based control strategy is designed and verified under different test cycles. The simulation results indicate that compared with the traditional manual transmission vehicle, the fuel economy of the vehicle equipped with PGS-FHEP can be improved by more than 50%, and the acceleration performance can be increased by 28.01%. Up to 60.61% of vehicle kinetic energy can be recovered by PGS-FHEP, among which 37.85% can be directly captured by the energy storage flywheel. In addition, the battery charging power is reduced, which is beneficial to prolong the battery life.

Carbon fiber is a common waste building material, but its effect on the drying and cracking properties of clay materials is unknown. In this paper, crack rate and fractal dimension are used to characterize the influence of waste carbon fiber materials on the development of soil cracking. With the rise in carbon fiber content to 0.2%, 0.4% and 0.6%, the crack rate of soil cracking decreased by 7.9%, 17.3% and 23.3%, respectively, while the fractal dimension of soil cracking decreased by 2.4%, 8.7% and 21.2%, respectively. Accordingly, the critical moisture content of the soil samples increased by 33.2%, 110% and 151%, and the time of the soil constant evaporation stage decreased by 5.1%, 13.8% and 34.5%, respectively. When carbon fiber is combined with soil, carbon fiber will increase the interface bonding strength, friction and interlocking force, effectively inhibiting the cracking of soil, and it provides a channel for water transport in the soil in the early stage.

Carbon-based supercapacitors (SCs) have limited energy density due to sluggish mass diffusion and restricted charge accumulation. To increase the energy density of carbon-based SCs, attention must be paid to the factors of specific capacitance and electrochemical stability window. This review summarizes recent signs of progress in carbon-based materials, including specific surface area, pore structure regulation, heteroatom doped, and carbon composites. In addition, we discuss aqueous, organic, and ionic liquid electrolytes that affect the electrochemical stability window of SCs. Finally, the possibilities for achieving synergy in electrode/electrolytes are summarized via enhancing the pseudocapacitance contribution and developing high-voltage window electrolytes.

Fractal geometry is a geometry that focuses on irregular geometric forms and can quantitatively describe rough and uneven surfaces and interfaces. As the main material for making natural fiber geotextile, rice straw fiber can reduce the direct impact of rainfall on soil and reduce the intensity of hydraulic erosion. This study investigates whether the use of rice straw fiber as an additive to reinforce arid soil can inhibit moisture evaporation and prevent cracking. Samples with different fiber contents added (0%, 1%, 2%, and 4%) are placed in an environmental chamber to simulate the effects of an arid climatic condition and control the temperature and humidity levels. The cracking process of the samples is recorded by using a digital camera, and the parameters of the evaporation and cracking processes are quantitatively examined through digital image processing. The results show that all of the samples with fiber have a higher residual water content and can retain 31.4%, 58.5%, and 101.9% more water than without the fibers, respectively. Furthermore, both the primary and secondary cracks as well as crack networks are inhibited in samples with a higher fiber content, that is, 2% or 4% fiber contents. The samples reinforced with fiber also have a smaller crack ratio. Compared with the samples without straw fiber, the final crack ratio of the samples with 1%, 2%, and 4% fiber is reduced by 8.05%, 24.09%, and 35.01% respectively. Finally, the final fractal dimensions of the cracks in samples with fiber contents are also reduced by 0.54%, 5.50%, and 6.40% for the samples with 1%, 2%, and 4% fiber, respectively. The addition of natural fiber as an additive to reduce evaporative cracking in soil can: (1) reduce the soil porosity; (2) enhance the binding force between the soil particles; and (3) block the hydrophobic channels. Therefore, the addition of rice straw fiber to soil can effectively reduce soil evaporation and inhibit soil cracking.

PNO1 (Dim2 or Rrp2 or YOR145), a highly conserved regulator of ribosome assembly from yeast to mammals, is involved in forming the 90S pre-ribosome and plays an essential role in the late stage of 40S small subunit maturation. Recent studies have found that PNO1 is involved in the progression of a variety of tumors and is highly expressed in colorectal, lung, esophageal, glioma, and breast cancer and is associated with poor prognosis. In tumors, PNO1 mainly promotes cell proliferation, invasion, and autophagy and inhibits apoptosis by regulating the P53 pathway, FAK/AKT pathway, Notch signaling pathway, and MAPK signaling pathway. The high expression of PNO1 in various tumors may be reduced by the regulation of early B cell factor 1 (EBF1), transcription factor MYC, miR-340-5p, and the drug celecoxib inhibiting tumor proliferation, invasion and migration, and autophagy, promoting apoptosis. This article reviews the structure and function of PNO1, related molecular pathways, and its regulatory role in tumor formation and discusses its possibility as a molecular target for tumor therapy.

Abstract Background Corneal neovascularization (CNV) is an important disease that causes blindness. Secretogranin III (Scg3) has emerged as a new influencing factor of neovascularization. This study analyzed the Scg3 antibody’s inhibitory effect on CNV and and explored its preliminary mechanism. Methods Human umbilical vein endothelial cells (HUVECs) were treated with Scg3 and anti-Scg3. Cell proliferation, wound healing migration and tube formation assays were performed. Healthy adult New Zealand rabbits were randomly selected to be alkali burned and establish the corneal neovascularization (CNV) model. The rabbits were randomly divided into 3 groups (the high concentration group, low concentration group and control group). Different doses of anti-Scg3 and PBS were administered to the rabbits. Clinical examinations, immunostaining, quantitative real-time polymerase chain reaction (qPCR) and western blotting analyses were performed postoperatively. Results In the in vitro study, the Scg3 antibody mixture inhibited Scg3-induced endothelial cell proliferation and angiogenesis. In the in vivo study, significant CNV was observed in the control group. Confocal microscopy also revealed considerable active neovascularization in the control group. There was no obvious CNV growth in the high concentration group. Additionally, CD31, LYVE1 and CD45 expression was significantly inhibited after treatment with a high concentration of Scg3 antibody. The qPCR and western blotting analyses revealed that the levels of ERK in the low concentration group and high concentration group were higher than those in the control group at 7 days and 14 days. The levels of VEGF in the control group were significantly increased compared with those in the high concentration group. In all three groups, the levels of Akt were not significantly different at any time point. Conclusion The expression of Scg3 could affect the growth of HUVECs in vitro. Treatment with a high concentration (0.5 µg/mL) of Scg3 antibody reduced the inflammatory response and inhibited the growth of corneal neovascularization after corneal alkali burn injury in rabbits. The MEK/ERK pathway might play an important role in the inhibitory effect of anti-Scg3.

In this paper, the evaporation and cracking characteristics of soils reinforced with straw and polypropylene fibers are studied. The changes in moisture content during evaporation are measured by using a high precision platform scale and the development of surface cracks is captured with a digital camera. The results are analyzed by using a GIS (Geographic Information System) software and the crack ratio and fractal dimension of the cracks are calculated. The results show that the final average moisture content after evaporation of the soils with straw and polypropylene fibers is increased by 69.90% and 49.75%, respectively, compared with the soil without fibers. The rate of evaporation can be divided into three stages: Stage I: Initially stable; Stage II: Decreases rapidly, and Stage III: Decreases slowly and tends to be stable. The time of the appearance of the first crack in the soil without fibers is earlier than that in the soils with fiber reinforcements. The final crack ratio of the soils with straw and polypropylene fibers is reduced by 6.79% and 14.16% compared to the soil without fibers. Therefore, adding fiber to soil can reduce water evaporation and inhibit cracking which provides a technique for improving soils in arid areas.

We show theoretically that the characteristic modes of dielectric resonator antennas (DRAs) must be capacitive in the low frequency limit and that as a consequence of this constraint and the Poincaré Separation Theorem, the modes of any DRA consisting of partial elements of an encompassing super-structure with the same spatial material properties cannot resonate at a lower frequency than the encompassing structure. Thus, design techniques relying on complex sub-structures to miniaturize the antenna, including topology optimization and meandered windings, cannot apply to DRAs. Due to the capacitive nature of the DRA modes, it is also shown that the Q factor of any DRA sub-structure will be bounded from below by that of the super-structure at frequencies below the first self-resonance of the super-structure. We demonstrate these bounding relations with numerical examples.

Abstracts Background Diabetic retinopathy (DR) is one of the most common chronic microvascular complications of diabetes. Many studies have suggested that genetic factors are important in the context of DR. This study evaluated the associations of GWAS (Genome-wide association study) -identified DR-associated SNPs in a Chinese population in Guangxi Province with type 2 diabetes mellitus (T2DM). Methods A total of 386 hospitalized T2DM patients without proliferative diabetic retinopathy (PDR) and 316 hospitalized T2DM patients with PDR were included in this case–control study. Four tag SNPs, including rs1800896 in the IL-10 gene, rs2010963 in the VEGFA gene, rs2070600 in the RAGE gene and rs2910164 in the miR-146a gene, were examined using KASP (kompetitive allele specific PCR) genotyping assays. Results There were no significant differences in the genotype or allele frequencies of the miR-146a polymorphism (rs2910164) between subjects with PDR and those without DR. The TC genotype of rs1800896 was determined to be associated with an increased risk of PDR (the odds ratio (OR) was 2.366, with a 95% confidence interval (CI) ranging from 1.144 to 4.894). The CG genotypes of rs2010963 was associated with an decreased risk of PDR (the OR was 0.588, with a 95% CI ranging from 0.366 to 0.946). Regarding rs2070600, 2 genotypes (TT and CT) were associated with a decreased risk of PDR (the OR of the TT genotype was 0.180, with a 95% CI ranging from 0.037 to 0.872, and the OR of the CT genotype was 0.448, with a 95% CI ranging from 0.266 to 0.753). Conclusions The rs1800896 polymorphisms in the IL-10 gene, rs2010963 in the VEGFA gene and rs2070600 in the RAGE gene are associated with the risk of PDR in the Han Chinese population of Guangxi Province. Our findings provide suggestive evidence that these polymorphisms may be involved in the pathogenesis of PDR and should be investigated further.

In recent years, it has been determined that primitive myxoid mesenchymal tumors of infancy (PMMTI) are solid tumors. To date, very few cases of PMMTI have been reported, and there is no consensus regarding treatment. To provide additional references, it is necessary to collect and report the diagnoses and treatment outcomes of related cases. We report the case of a 38-day-old girl who presented with a 5-cm purple tumor in the right shoulder. Upon hospital admission, the patient received an intratumoral injection of bleomycin after diagnosis of a possible lymphangioma. 10 days after the treatment, the tumor began to develop inflammation and necrosis, resulting in a clear demarcation between the tumor and surrounding tissue. Hence, during the second hospitalization, we performed a successful tumor resection. Postoperatively, the tumor was pathologically diagnosed as PMMTI. 3 months after excision, the patient showed no local recurrence on re-examination. To the best of our knowledge, this is the first report of a PMMTI in which bleomycin, or other similar chemotherapeutic drugs, have been injected into tumors. This result offers novel insights into the treatment of PMMTI. Injection therapy with bleomycin and similar chemotherapeutics may result in specific responses to PMMTI, which may help in developing better surgical conditions or improving outcomes in non-surgical patients.

BackgroundWhether intensity-modulated radiotherapy (IMRT) can enhance the efficacy of the programmed death (PD)-1 inhibitors combined with anti-angiogenic therapy for hepatocellular carcinoma (HCC) is unclear. Therefore, we conducted this multicenter retrospective study to investigate the efficacy of the combination of PD-1 inhibitors with anti-angiogenic therapy and IMRT.MethodsFrom April 2019 to March 2022, a total of 197 patients with HCC [combination of PD-1 inhibitors with anti-angiogenic therapy and IMRT (triple therapy group), 54; PD-1 inhibitors plus anti-angiogenic therapy (control group), 143] were included in our study. Propensity score matching (PSM) was applied to identify two groups with similar baselines. The objective response rate (ORR), overall survival (OS), and progression-free survival (PFS) of the two groups were compared before and after matching.ResultsPrior to PSM, the triple therapy group had higher ORR (42.6% vs 24.5%, P = 0.013) and more superior median OS (mOS) (20.1 vs 13.3 months, P = 0.009) and median PFS (mPFS) (8.7 vs 5.4 months, P = 0.001) than the control group. Following PSM, the triple therapy group still exhibited better mPFS (8.7 vs 5.4 months, P = 0.013) and mOS (18.5 vs 12.6 months, P = 0.043) than the control group. However, the ORR of the two groups was similar (40% vs 25%, P = 0.152). No significant difference was observed in the treatment-related adverse events between the two groups (P < 0.05 for all). ConclusionsThe combination of PD-1 inhibitors with anti-angiogenic therapy and IMRT for HCC is a promising regimen.

Colon cancer (CC) is a multistage disease and one of the most common cancers worldwide. Establishing an effective treatment strategies of early colon cancer is of great significance for preventing its development and reducing mortality. The occurrence of colon cancer is closely related to changes in the intestinal flora structure. Therefore, remodelling the intestinal flora structure through prebiotics is a powerful approach for preventing and treating the occurrence and development of colon cancer. Isomaltooligosaccharides (IMOs) are often found in fermented foods and can directly reach the gut for use by microorganisms. In this study, a rat model of early colon cancer (DMH) was established by subcutaneous injection of 1,2-dimethylhydrazine, and the model rats were fed IMOs as a dietary intervention (DI). The untargeted faecal metabolomics, gut metabolome and intestinal function of the model rats were investigated. The results showed that DMH, DI and IMOs alone (IMOs) groups exhibited gut microbial community changes. In the DI group, there was an increased abundance of probiotics (Lactobacillus) and decreased abundance of CC marker bacteria (Fusobacterium). The key variations in the faecal metabolites of the DI group included decreased levels of glucose, bile acids (including deoxycholic acid and chenodeoxycholic acid) and amino acids (including L-glutamic acid and L-alanine). In addition, dietary intake of IMOs attenuated the intestinal inflammatory response, improved the intestinal microecological environment, and slowed the development of DMH-induced early CC in rats. This work provides a theoretical basis and technical support for the clinical prevention or treatment of CC with prebiotics.

AimA programmed death 1 (PD-1) inhibitor coupled with radiotherapy and antiangiogenic therapy is a potential therapeutic strategy for advanced hepatocellular carcinoma (HCC). We aimed to determine if circulating tumor cells (CTCs) positive for programmed death-ligand 1 (PD-L1) could be employed as a predictive biomarker in HCC patients receiving triple therapy.MethodsIn this study, HCC patients received a PD-1 inhibitor in combination with intensity-modulated radiotherapy (IMRT) and antiangiogenic therapy. Following IMRT, the PD-1 inhibitor was administrated once every 3 weeks, while the antiangiogenic drug was given once a day. Treatment was continued until the disease progressed. Two mL of peripheral blood was collected at baseline, 1 month, and 3 months after treatment for CTC enrichment using the CytoSorter® system with a CytoSorter™ CTC PD-L1 Kit (Watson Biotech., China).ResultA total of 47 HCC patients receiving the triple therapy were enrolled in this study. Patients with < 2 PD-L1+ CTCs at baseline had a higher objective response rate (ORR) and longer overall survival (OS) than those with ≥ 2 PD-L1+ CTCs (56.5% vs. 16.7%, p = 0.007; not reach vs. 10.8 months, p = 0.001, respectively). The count of PD-L1+ CTCs was found to be an independent predictive biomarker of OS. Furthermore, the objective response was more likely to be achieved in patients with a dynamic decrease in PD-L1+ CTC counts at 1 month after treatment.ConclusionsOur study demonstrated that PD-L1+ CTCs could be a predictive biomarker for HCC patients receiving PD-1 inhibitors in combination with IMRT and antiangiogenic therapy.

Abstract Background To investigate the impact of protective measures and isolation on respiratory tract infections in children during the COVID-19 outbreak. Methods We extracted data on outpatient visits and respiratory infection visits, and tests of respiratory viruses (adenovirus (ADV), influenza A (FluA), influenza B (FluB) and respiratory syncytial virus (RSV)) from electronic healthcare records in Children’s Hospital, Zhejiang University School of Medicine during the COVID-19 outbreak (January–April, 2020), compared with those in 2018 and 2019 during the same periods. Results We found that outpatient visits in January, 2020 was comparable with those in 2018 and 2019, but decreased by 59.9% (288,003 vs. 717,983) and 57.4% (288,003 vs. 676,704), respectively during the period of February-April, 2020, as compared with the same periods in 2018 and 2019. The total number of respiratory tract infections from January to April 2020 decreased by 65.7% (119,532 vs.348,762) and 59.0% (119,532 vs.291,557), respectively compared with the same periods in 2018 and 2019. The proportion of respiratory tract infections during the outbreak also dropped compared with the same periods in 2018 and 2019 (P

To explore the differences in hoarding strategies of rodents for different seeds in various seasons, we labeled and released the seeds of Pinus koraiensis, Corylus mandshurica, Quercus mongolica and Prunus sibirica in temperate forests of Northeast China and investigated the fate of the seeds in spring and autumn. The analysis showed that the hoarding strategies of the rodents varied substantially between seasons. The seeds were consumed faster in the spring than in the autumn. More than 50% of the seeds in the two seasons were consumed by the 16th day. It took 36 days to consume 75% of the seeds in the spring and 44 days in the autumn. The rate of consumption of the seeds in the spring was greater than in the autumn, and the rate of spread of the seeds was greater in the autumn. The distances of removal for the consumption and dispersal of seeds in the spring (3.26 ± 3.21 m and 4.15 ± 3.52 m, respectively) were both shorter than those in the autumn (3.74 ± 3.41 m and 4.87 ± 3.94 m, respectively). In addition, the fate of different seeds varied significantly owing to differences in hoarding strategies. The seeds of the three preferred species, P. koraiensis, C. mandshurica, and Q. mongolica, were quickly consumed. More than 90% of the seeds of these species were consumed. Only 21% of Pr. sibirica seeds were slowly consumed, and the two seasons had the same seed consumption rate patterns: the consumption rate of P. koraiensis seeds was the highest, followed by C. mandshurica, then Q. mongolica, and finally Pr. sibirica. The median removal times of the two seasons were different, but the rules were the same: P. koraiensis was the shortest, followed by C. mandshurica, and the third was Q. mongolica. In both seasons, the most predated in situ seeds were those of P. koraiensis; the most hoarded seeds were those of C. mandshurica, and the most unconsumed seeds were those of Pr. sibirica.

The guided tissue regeneration (GTR) technique is a promising treatment for periodontal tissue defects. GTR membranes build a mechanical barrier to control the ingrowth of the gingival epithelium and provide appropriate space for the regeneration of periodontal tissues, particularly alveolar bone. However, the existing GTR membranes only serve as barriers and lack the biological activity to induce alveolar bone regeneration. In this study, sericin-hydroxyapatite (Ser-HAP) composite nanomaterials were fabricated using a biomimetic mineralization method with sericin as an organic template. The mineralized Ser-HAP showed excellent biocompatibility and promoted the osteogenic differentiation of human periodontal membrane stem cells (hPDLSCs). Ser-HAP was combined with PVA using the freeze/thaw method to form PVA/Ser-HAP membranes. Further studies confirmed that PVA/Ser-HAP membranes do not affect the viability of hPDLSCs. Moreover, alkaline phosphatase (ALP) staining, alizarin red staining (ARS), and RT-qPCR detection revealed that PVA/Ser-HAP membranes induce the osteogenic differentiation of hPDLSCs by activating the expression of osteoblast-related genes, including ALP, Runx2, OCN, and OPN. The unique GTR membrane based on Ser-HAP induces the differentiation of hPDLSCs into osteoblasts without additional inducers, demonstrating the excellent potential for periodontal regeneration therapy.

As the essential regulator of intestinal bacterial diversity, probiotics are a potential treatment for chronic high-salt diet (HSD)–induced metabolic dysfunction. Probiotic cells entrapped in microgels have been confirmed as being more effective than free cells in protecting bacteria against unfavorable conditions, that is, enhancing their stress resistance. This study explored the physiological mechanism by which probiotic microgels relieve HSD–induced hepatorenal injury. Herein, Lactobacillus rhamnosus was encapsulated in alginate-chitosan microgels which the percentage of alginate/chitosan was applied 1.5:0.5 (w/w) in this system, and the encapsulation significantly improved the probiotic viability in simulated gastrointestinal conditions. Mice were fed an HSD with L. rhamnosus (SDL) or L. rhamnosus microgels (SDEL). After 8 weeks of administration, dietary sodium was confirmed as inducing the hepatic and renal damages in mice, based on indicators, including serum biomarker levels, histopathological features of tissues, and pro-inflammatory cytokine contents in blood levels. However, the serum levels of urea nitrogen, creatinine, uric acid, glutamic-pyruvic transaminase, glutamic-oxalacetic transaminase, and alkaline phosphatase in the SDL and SDEL-fed mice were significantly lowered compared to the HSD-fed mice, especially in the SDEL group. HSD increased the abundances of Anaeroplasma, Enterorhabdus, Parvibacter, and Bacteroides, while the microgels increased the abundances of Lactobacillus, Bifidobacterium, Mucispirillum, and Faecalibaculum. Significant variations of fecal metabolome were validated for SDEL-treated mice, containing those linked to entero-hepatic circulation (e.g., cholic acid), carbohydrate metabolism (i.e., L-lactic acid), and increased antioxidants including citric acid. Furthermore, the probiotic microgels ameliorated intestinal damage by improving barrier and absorption functions. These results augmented existing knowledge on probiotic application for salt toxicity.

BackgroundMucous cyst of the distal interphalangeal joint (DMC) or interphalangeal connection of the thumb is common in middle-aged and elderly people, and it often occurs in the fingers of people with osteoarthritis (OA). Although there are many conservative treatments, DMC is usually treated by surgery. The common complications of surgical treatment are recurrence of DMC and skin necrosis. This article introduces the method and clinical effect of osteophyte excision and joint debridement in the treatment of DMC of the distal interphalangeal (DIP) joint.MethodsIn total, 19 cases of affected fingers made an 'S' incision in the DIP joint under local anesthesia to remove the osteophyte of the DIP joint, clean the dorsal joint capsule, wash the joint, and retain only the bilateral collateral ligament and extensor tendon device. It is suspected that the injured finger of the extensor tendon should be protected by external fixation.ResultsOut of 15 patients, 1 patient presented with partial skin necrosis that healed after dressing changes while the other patients recovered well. The visual analog scale (VAS) scores of all affected fingers after surgery were lower than those before the surgery (VAS score: 4.93 ± 0.88 vs. 4.07 ± 1.03, p < 0.05). The range of motion (ROM) of the affected finger decreased in one patient, and the post-operative activity of the other fingers increased in varying degrees (ROM: 67.60 ± 5.40 vs. 71.27 ± 7.06, p > 0.05).ConclusionsUsing osteophyte excision and joint debridement to treat DMC can avoid skin necrosis caused by cyst removal and can avoid the recurrence of DMC to the greatest extent, so it is a safe and effective way of treatment.

Engineering geological practice and investigation are important measures for geological fluid and engineering geological research; the practice route has an important impact on the achievement of research objectives. In this study, the practice route is mainly affected by four primary indicators: abundance of geological resources, rationality of the practice route, effect of practice, and the accommodation conditions. The four primary indicators include 13 secondary indicators, and each secondary indicator can be divided into positive and negative random variables, which is the specific content of the evaluation. In order to collect the feedback data of participants on the practice route, a questionnaire was constructed based on indicators at all levels. According to the results of the questionnaire, the mean and standard deviation of each random variable are counted and the distribution law of probability density is fitted. A performance function is constructed to represent the approval status of participants for each indicator. Considering the influence of 26 random variables, a multifactor evaluation method for the engineering geology practice route is proposed based on the reliability analysis method. This method can be used to analyze the approval status of random factors, search for the shortcomings of the route, and provide an effective method to improve the rationality of the route. The conclusion shows that this study provides a solution to evaluate fuzzy problems in engineering geological practice, especially if the problems are difficult to be quantified through experiment or measurement.

Bagasse is the residue after juicing sugarcane, and bagasse is a recyclable biological resource that can be used in many ways. Under arid climatic conditions, the clay material shrinks and loses water. Many crisscross drying shrinkage cracks formed on the surface and inside the soil will affect the stability of the soil. In this article, the cracking characteristics of clays with different bagasse contents during the evaporation process have been studied. The cracks were extracted and calculated by digital image processing technology, and the crack characteristics of samples with different bagasse contents were studied by fractal dimension and crack entropy. The results show that when moisture content maintains 34%, the clay material forms only one main crack without bagasse, forms no crack with bagasse content of 9%, and forms a crack network with the bagasse content of 3%. Adding bagasse to the clay can advance the cracking time of the clay, and different contents of bagasse have different effects on the cracking time of the clay. Among these five experimental groups, the clay was affected the most with 3% bagasse content, while the least effect happened with 6% bagasse content. The time can be advanced when the clay crack entropy appears and increases the size of the crack entropy.

Engineering geology applies geological theories and methods to the practice of engineering activities, evaluates the engineering geological conditions of the engineering site through engineering geological investigation and comprehensive research of theories, solves the engineering geological problems related to engineering activities, predicts and demonstrates the occurrence and development laws of engineering geological problems in the engineering activity area, and puts forward technical measures for prevention and control, so as to contribute to the planning, design, and construction and provide necessary geological and technical data for use and maintenance. Based on the theory of multiattribute decision-making, this paper puts forward the evaluation index system of engineering geology teaching quality in applied universities. A curriculum teaching quality evaluation index system is constructed, which is composed of four main indexes: online resources and teaching, offline teaching process, classroom teaching quality evaluation, and classroom teaching quality evaluation. Furthermore, 11 second-class indices and 28 third-class indices are considered. The judgment matrices and membership degree of each attribute are obtained through use of a questionnaire, and the total weight of each subitem is calculated using the analytic hierarchy process. The calculation results show that the classroom instructional quality of the engineering geology course can be considered excellent; furthermore, other courses could also be evaluated using the same method, where those with low evaluation results can be further improved. Using the fuzzy comprehensive evaluation method based on the analytic hierarchy process, we evaluate the instructional quality, comprehensively consider the nonlinear and fuzzy characteristics of evaluation factors, can scientifically calculate the weight value of each evaluation index, and combine qualitative and quantitative aspects, in order to objectively provide an evaluation of the classroom instructional quality of teachers, which is conducive to the high-quality construction of university courses.

ObjectiveSystemic lupus erythematosus (SLE) is an autoimmune disease with complex etiology that is not yet entirely understood. We aimed to elucidate the mechanisms and therapeutic potential of microRNAs (miRNAs) in SLE in a Tibetan population.MethodsPeripheral blood mononuclear cells from SLE patients (n = 5) and healthy controls (n = 5) were used for miRNA–mRNA co-sequencing to detect miRNAs related to immune abnormalities associated with SLE. Luciferase reporter assay was used to identify potential targets of candidate miRNA. The target genes were verified in miRNA-agomir/antagomir transfection assays with multiple cells lines and by expression analysis. The effects of candidate miRNA on monocyte and macrophage activation were evaluated by multiple cytokine profiling. Neutrophil extracellular traps (NETs) formation was analyzed in vitro by cell stimulation with supernatants of monocytes and macrophages transfected with candidate miRNA. The rodent MRL/lpr lupus model was used to evaluate the therapeutic effect of CXCL2Ab on SLE and the regulation effect of immune disorders.ResultsIntegrated miRNA and mRNA expression profiling identified miRNA-4512 as a candidate miRNA involved in the regulation of neutrophil activation and chemokine-related pathways. MiR-4512 expression was significantly reduced in monocytes and macrophages from SLE patients. MiR-4512 suppressed the TLR4 pathway by targeting TLR4 and CXCL2. Decreased monocyte and macrophage miR-4512 levels led to the expression of multiple proinflammatory cytokines in vitro. Supernatants of miR-4512 antagomir-transfected monocytes and macrophages significantly promoted NETs formation (P < 0.05). Blocking of CXCL2 alleviated various pathogenic manifestations in MRL/lpr mice, including kidney damage and expression of immunological markers of SLE.ConclusionsWe here demonstrated the role of miR-4512 in innate immunity regulation in SLE. The effect of miR-4512 involves the regulation of monocytes, macrophages, and NETs formation by direct targeting of TLR4 and CXCL2, indicating the miR-4512-TLR4-CXCL2 axis as a potential novel therapeutic target in SLE.

Soil drying cracking is the most common natural phenomenon affecting soil stability. Due to the complexity of the geometric shapes of soil cracks during the cracking process, it has become a major problem in engineering science. The extremely irregular and complex crack networks formed in civil engineering materials can be quantitatively investigated using fractal theory. In this paper, fractal dimension is proposed to characterize the drying cracking characteristics of composite soil by adding recycled waste brick micro-powder. At the same time, the concept of the probability entropy of cracking is introduced to quantify the ordered state of crack development. Correspondingly, the endpoint value of probability entropy was solved mathematically, and the meaning of the probability entropy of cracking was clarified. In this study, the fracture fractal characteristics of composite soil mixed with different materials were first investigated. Then, five groups of composite soil-saturated muds with added recycled waste brick micro-powder of different contents were prepared in the laboratory. Using the evaporation test under constant temperature and humidity, the change rules of the fractal dimensions, probability entropy, crack ratios, and water contents of cracks during the cracking process of the soil samples were obtained. The results show that: (1) on the whole, the fractal dimensions of the soil samples added with recycled waste brick micro-powder of different contents increased over time, and the fractal dimensions of the soil samples without recycled waste brick micro-powder were obviously larger than those of the soil samples with recycled waste brick micro-powder. With the increase in the content of recycled waste brick micro-powder, the maximum fractal dimension decreased in turn. The maximum fractal dimensions of the five groups of soil samples were 1.74, 1.68, 1.62, 1.57, and 1.45. (2) The change trends of the probability entropy and fractal dimensions were similar; both of them showed an upward trend over time, and the probability entropy of the soil samples without recycled waste brick micro-powder was greater than that of the soil samples with recycled waste brick micro-powder. With the increase in the contents of recycled waste brick micro-powder, the probability entropy decreased in turn. The maximum values of the crack probability entropy of the five groups of soil samples were 0.99, 0.92, 0.87, 0.83, and 0.80. (3) Under the action of continuous evaporation, the moisture contents of the soil samples gradually decreased over time, while the crack ratios increased over time. To sum up, both from the perspective of the development process of the cracks of the soil samples and from the perspective of the final stable crack networks of the soil samples, the geometric shapes of the cracks of the soil samples without recycled waste brick micro-powder were the most complex. With the increase in the content of recycled waste brick micro-powder, the fractal characteristics of the cracks gradually changed from complex to simple.

Soil surfaces form complex crack networks as a result of water loss and shrinkage. A crack network destroys the integrity of the soil and becomes the main factor affecting rainfall infiltration, slope instability and soil integrity. In this paper, a soil fracture network is quantified using fractal characteristics and fractal dimensions, and the soil fracture network is identified and calculated using digital image processing technology. The fracture network of silty clay with different setaria viridis root content is studied during the process of evaporation. Saturated mud is prepared by taking soil samples and collecting setaria viridis roots. The content of setaria viridis roots in each saturated mud sample is 0 g, 0.1 g, 0.2 g and 0.3 g. In the artificial climate environment simulation system, thin-layer root soil is dried by controlling the temperature and humidity to simulate dry climate conditions. During the test, the crack development process is recorded using a digital camera. The results show that when the root content is 0, 0.1 g, 0.2 g and 0.3 g, the water content values when a fissure is generated are 35.2%, 41.2%, 42% and 46.4%, and the initial fractal dimension values are 1.100, 1.106, 1.112 and 1.115, respectively. The fractal dimension value increases rapidly in the early stage of fissure generation, and it reaches the maximum value when the water content reaches 13.66%, 15.2%, 15.66% and 17.98%, respectively. According to the change law of the fractal dimension, the fractal dimension increases rapidly following the initial appearance of the fracture, and, with a continuous reduction in water content in the later stage, the fracture characteristics gradually stabilize, and the change rate of the fractal dimension becomes slow.

Under the influence of internal and external factors, a fracture network is easily generated in concrete and rock, which seriously endangers project safety. Fractal theory can be used to describe the formation and development of the fracture network and characterize its structure. Based on the flow balance in the node balance field, Forchheimer’s law is introduced to derive the control equation of high-velocity non-Darcy flow in the fracture network. The fracture network is established according to the geological parameters of Sellafield, Cumbria, England. A total of 120 internal fracture networks are intercepted according to 10 dimensions (1 m, 2 m, …, 10 m) and 12 directions (0°, 30°, …, 330°). The fractal dimension, equivalent hydraulic conductivity (K), and equivalent non-Darcy coefficient (β) of the fracture network are calculated, and the influence of the fractal dimension on K and β is studied. The results indicate that the fractal dimension of the fracture network has a size effect; with the increase in the size, the fractal dimension of the fracture network undergoes three stages: rapid increase, slow increase, and stabilization. In the rapid increase stage, K and β do not exist. In the slow increase stage, K exists and is stable, and β does not exist. In the stabilization stage, K and β both exist and are stable. The principal axes of the fitted seepage ellipses of K and β are orthogonal, and the main influencing factors are the direction and continuity of the fracture.

In recent years, the irregular cracks formed during the damage evolution of civil engineering materials have been able to be quantitatively described by using fractals. In this study, the fractal characteristics of the desiccation cracking of soil were investigated under different substrate contact and permeability conditions through a natural drying test in the laboratory. Three kinds of base contact conditions of soil, namely, grease, geomembrane, and geotextile, were designed, and two samples for each contact condition, including one parallel sample, were used. The continuous drying experiment was carried out at a constant ambient temperature. The crack morphology under different spacings was analyzed quantitatively using digital image processing technology. The fractal dimensions of three soil substrate contact conditions (grease, geomembranes, and geotextiles) were between 1.238 and 1.93. When the crack network on the soil surface stops developing, the fractal dimensions under the three experimental conditions are 1.88, 1.93 and 1.79, respectively. In the final state of crack development, the crack intensity factor of the sample with grease at the bottom is 2.99% and 4.02% higher than that of the sample with geomembranes and geotextiles at the bottom, respectively. The residual water contents of the samples with bottom contact conditions of grease, geomembrane, and geotextile increase successively, which are 3.12%, 5.76% and 9.71%, respectively. The effects of interface friction and permeability on soil cracking behavior are analyzed, and the evolution characteristics and formation mechanisms of cracks in soil are revealed.

Background: T follicular helper cells (Tfh cells) play an important role in activating B lymphocytes and may associate with idiopathic Optic Neuritis (ON) and Neuromyelitis Optica Spectrum Disorders (NMOSD).Objective: This study aimed to examine the potential role of Tfh cells in pathogenesis of idiopathic ON and NMOSD.Methods: Circulating CD4+CXCR5+ and CD4+CXCR5+PD-1+ cells in 46 idiopathic ON and 68 NMOSD patients as well as 28 healthy controls were examined by flow cytometry before treatment. Serum AQP4 antibody, Expended Disability Status Scale (EDSS) and Visual Outcome Scale (VOS) were detected before and after treatment.Results: The percentages of circulating CD4+CXCR5+ and CD4+CXCR5+PD-1+Tfh cells in CD4+ cells (%) were significantly increased in idiopathic ON and NMOSD compared with those of healthy controls (p < 0.01). No significant difference of Tfh cells in blood and cerebral spinal fluid (CSF) was found between ON and NMOSD patients. The percentages of CSF, CD4+, CXCR5+, and CD4+CXCR5+PD-1+ cells in CD4+ cells (%) were positively correlated with those of the blood (r = 0.5781, r = 0.6079, p = 0.0076, and p = 0.0045, respectively). EDSS scores of NMOSD group were higher than those of ON group and the time course of NMOSD patients was longer than that of ON patients (p < 0.01). After methylprednisolone treatment, both EDSS and VOS scores were significantly decreased at discharge compared with before treatment (p < 0.01). There was no significant correlation among Tfh cell percentages in CD4+ cells, CSF leukocytes, CSF protein, annual recurrence rate, EDSS and VOS scores between two groups (p > 0.05).Conclusion: The Circulating T follicular helper cells were increased in both idiopathic ON and NMOSD.

This report describes an 8-year-old male who presented with clinical manifestations including systemic edema, heavy proteinuria, hypoproteinemia, and persistent hypocomplementemia. Arachnoid cysts and focal nodular hyperplasia were also detected. Imaging examination and renal biopsy were performed, and Abernethy malformation type II with immune complex-mediated membranoproliferative glomerulonephritis was considered the diagnosis. Due to the persistence of embryonic vessels, Abernethy malformation is a rare congenital vascular malformation of the splanchnic venous system, which can be classified as type I (end-to-side shunt) and type II (side-to-side shunt). Abernethy malformation with glomerulonephritis remains extremely rare. In the patient described, glomerulonephritis mediated by immune complex with “full-house” positive immunohistochemistry was confirmed on renal biopsy. In addition, he was treated with glucocorticoids and tacrolimus. Whether surgical treatment is necessary should be determined according to the state of the disease in the later stages. The present case reflects the association between the congenital portosystemic shunt and the renal region and, to the authors' knowledge, may be the first report to describe arachnoid cysts as a symptom of Abernethy malformation.

The mechanism of water flow in and around the bulkheads and the surrounding rock is studied for Panel No. 21102 in the Sanhejian coal mine in Xuzhou, China. Based on an analysis of the properties of the bulkheads and the surrounding rock, three types of water conducting pathways are identified: (1) a water conducting pathway at the interface between the bulkhead and the surrounding rock; (2) a water conducting pathway in the faults of the rock; and (3) a water conducting pathway in the fractures of the rock. The possibility of these three pathways for water flow at Panel No. 21102 is analyzed, and the connectivity coefficient of the water conducting pathway is determined. The expression for calculating the critical hydraulic gradient of the rock by using the connectivity coefficient in the water conducting pathways is presented which is based on the permeability and integrity of the rock. The ratios of the critical hydraulic gradient to the steady state hydraulic gradient are calculated for 13 mines in China. An acceptable safety factor in controlling the water flow for the bulkhead is found to be 1.68. When the safety factor is less than 1.68, water leakage has occurred in a number of cases. Finally, changes in the water pressure in the bulkheads with time and changes in the seepage flow with time in the surrounding rock are analyzed. It is found that there is a good correlation between the rate of water flow and water pressure which confirms that water pressure plays a decisive role in controlling seepage from the rock in and around the bulkheads.

Soil contamination in the Panjiachong lead and zinc mining areas has become a severe problem in Hunan Province, China. As the traditional stabilization technology comes with soil degradation, it is urgent to find a novel binder that is more eco-friendly. It has been proved that biochar can immobilize heavy metals, but limited research has been conducted on the contaminated soil with high concentration. In this study, 5%, 8%, and 10% biochar derived from the rice straw were used to remediate contaminated soil with high concentration of lead and zinc. Portland cement (PC) was adopted as the control group. The results showed that after 56 d curing, the biochar-treated soil had a neutral pH and EC value and higher soil fertility compared with the PC-treated soil. The results from the toxicity characteristic leaching procedure test indicated that the biochar is more effective than PC on heavy metal immobilization. Germination index (GI) value was used to evaluate the phytotoxicity of the treated soil; the GI values of treated soil with 8% and 10% biochar were both higher than 80%, while all the PC-treated groups failed to achieve this GI value, which indicated the potential revegetation is applicable for the biochar-treated soil.

The study of engineering geology emphasizes the combination of theory and practice, and it highlights the comprehensive cultivation of curricular theory, curricular practice, and comprehensive skills. It is necessary to establish a set of effective methods to evaluate the achievement of training objectives to track, test, and improve the quality of curricular learning. In this paper, the principle of the fuzzy analytic hierarchy process based on entropy is used to construct an evaluation index system for the goal achievement degree of engineering geology courses, and the primary indicators mainly include knowledge, ability, and quality. Based on the actual situation, five curricular achievement levels are determined, that is, the comment set V = {very low, low, medium, high, very high}. Relying on the engineering geology course resource database of Xuchang University, the course goal achievement degree is evaluated, and the results show that the engineering geology course achievement degree is high. This method is suitable not only for the evaluation of the achievement of curricular objectives but also for the evaluation of the achievement of engineering education graduation requirements. This method can also help us find different courses and teaching weak links supporting the index points, indicate the direction and provide support for teachers to continuously improve their teaching and management methods, and effectively promote a continuous improvement in teachers’ teaching level and teaching quality.

Desiccation cracks form on the surface of foundation soils due to matric suction and surface shrinkage with water loss. This paper investigates the effect of tea waste on the change of water content and cracking characteristics of foundation soil during drying. Digital image processing was carried out based on laboratory experiments. The characteristics are monitored with a variation in water content. The effects of different amounts of tea waste on soil drying and cracking were obtained, in order to provide an efficient and new green sustainable material for improving soil evaporation cracking under drought conditions. The results show that the development of cracks of soil samples with tea waste can be categorized into three stages in accordance with the fractal dimension of the desiccation cracks: Stages I, II, and III. The desiccation cracks in Stage III are wider and longer than those in Stages I and II, however, the maximum fractal dimension and stability are also obtained in Stage III. The residual water content of the sample without tea waste is 1.5%. The residual water content of the samples containing 4% and 8% tea waste is 4.6% and 5.4%, respectively, which shows that the tea waste can effectively improve the residual water content of the foundation soil and the water holding capacity of the soil. The fractal dimension of cracks on the soil samples increases gradually with drying. The total length of cracks increases and the development of cracks is more complex. The cracking time of soil samples with different tea waste contents is different. The soil samples with 8% tea waste content crack first. Combined with the variation characteristics of water content, tea waste has water absorption and improves the water holding capacity and stability of foundation soil.

Over time and across space, the hydraulic conductivity, fractal dimension, and porosity of embankment soil have strong randomness, which makes analyzing seepage fields difficult, affecting embankment risk analysis and early disaster warning. This strong randomness limits the application of fractal theory in embankment engineering and sometimes keeps it in the laboratory stage. Based on the capillary model of porous soil, an analytical formula of the fractal relationship between hydraulic conductivity and fractal dimension is derived herein. It is proposed that the influencing factors of hydraulic conductivity of embankment soil mainly include the capillary aperture, fractal dimension, and fluid viscosity coefficient. Based on random field theory and combined with the embankment parameters of Shijiu Lake, hydraulic conductivity is discretized, and then the soil fractal dimension is approximately solved to reveal the internal relationship between hydraulic gradient, fractal dimension, and hydraulic conductivity. The results show that an increased fractal dimension will reduce the connectivity of soil pores in a single direction, increase the hydraulic gradient, and reduce the hydraulic conductivity. A decreased fractal dimension will lead to consistency of seepage channels in the soil, increased hydraulic conductivity, and decreased hydraulic gradient.

Purpose: To evaluate the effectiveness of various graft options for anterior cruciate ligament reconstruction using network meta-analysis. Methods: A medical literature search was conducted of PubMed, the Cochrane Library, Embase, SCOPUS, and Web of Science from their inception through March 1, 2019. The outcomes, including International Knee Documentation Committee (IKDC) form, Lachman test, Lysholm score, Pivot shift test, and Tegner score, were evaluated among graft options. Data extraction was carried out according to inclusion and exclusion criteria, and a network meta-analysis was performed using STATA 14.0. Results: A total of 45 trials with 3992 patients were included. The forest plots revealed no significant differences in IKDC, Lysholm, or Tegner score among the grafts. In Lachman score, a significant difference was found in the comparisons of hamstring tendon allograft (HT-AL) versus patellar tendon autograft (PT-AU) and HT-AL versus hamstring tendon autograft (HT-AU). In pivot shift test, PT-AU was superior to all the other grafts, and quadriceps tendon autograft (QT-AU) was superior to HT-AL and artificial ligament (Art-L) in the number of cases with negative results. According to surface under the cumulative ranking area (SUCRA), PT-AU had the highest probability to be the best intervention in Lachman test and Tegner score; tibialis anterior tendon allograft (TA-AL) in IKDC and Lysholm score; and QT-AU in pivot shift test. Based on the cluster analysis of SUCRA, PT-AU was considered the most appropriate intervention by IKDC and Lachman test. Conclusion: This study suggests that PT-AU may be the most appropriate graft for ACL reconstruction according to IKDC and Lachman test results. Level of Evidence: Level I, network meta-analysis of randomized controlled trials.

The blood-brain barrier (BBB) is a dynamic but solid shield in the cerebral microvascular system. It plays a pivotal role in maintaining central nervous system (CNS) homeostasis by regulating the exchange of materials between the circulation and the brain and protects the neural tissue from neurotoxic components as well as pathogens. Here, we discuss the development of the BBB in physiological conditions and then focus on the role of the BBB in cerebrovascular disease, including acute ischemic stroke and intracerebral hemorrhage, and neurodegenerative disorders, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and multiple sclerosis (MS). Finally, we summarize recent advancements in the development of therapies targeting the BBB and outline future directions and outstanding questions in the field. We propose that BBB dysfunction not only results from, but is causal in the pathogenesis of neurological disorders; the BBB is more a contributor to the disruption of CNS homeostasis than a victim in neurological disorders.

Host defense caerin 1.1 and 1.9 peptides, isolated from the glandular secretion of Australian tree frogs, the genus Litoria, have been previously shown to have multiple biological activities, including the inhibition of human papillomavirus (HPV) 16 early protein E7 transformed murine as well as human cancerous cell proliferation both in vitro and in vivo. However, the mechanism underlying their anti-proliferative activities against HPV18+ cervical cancer HeLa cells remains unknown. This study comparatively investigated the anti-proliferation on HeLa cells by caerin 1.1, 1.9, and their mixture, followed by confocal microscopy examination to assess the cellular intake of the peptides. Tandem mass tag labeling proteomics was employed to reveal the proteins that were significantly regulated by the peptide treatment in cells and cell growth environment, to elucidate the signaling pathways that were modulated. Western blot was performed to confirm the modulation of the pathways. Both caerin 1.1 and 1.9 highly inhibited HeLa cell proliferation with a significant additive effect compared to untreated and control peptide. They entered the cells with different magnitudes. Intensive protein-protein interaction was detected among significantly upregulated proteins. Translation, folding and localization of proteins and RNA processing, apoptosis process was significantly enriched post the treatments. The apoptotic signaling was suggested as a result of tumor necrosis factor-α (TNF-α) pathway activation, indicated by the dose-dependent elevated levels of caspase 3 and caspase 9. The epidermal growth factor receptor and androgen receptor pathways appeared inhibited by the peptides. Moreover, the activation of T-cell receptor derived from the quantitation results further implies the likelihood of recruiting more T cells to the cell growth environment post the treatment and more sensitive to T cell mediated killing of HeLa cells. Our results indicate that caerin 1.1 and 1.9 mediate apoptotic signals of HeLa cells and may subsequently enhances adaptive T cell immune responses.

Soil pollution due to acid contamination changes the chemical state of the soil and affects the water evaporation and desiccation cracking characteristics of the soil. The contamination of soils is becoming a serious problem due to increases in manufacturing, construction, and industrial activities, especially in and around urban areas. Soil pollution has become a global issue with serious and harmful impacts on the environment. The purpose of this paper is to present a study on the evaporation characteristics of soil contaminated with different acid concentrations. The result indicates that water evaporation in soils can be divided into three stages: the steady rate of evaporation, deceleration of evaporation, and residual evaporation stages. With increases in acid concentration, there is critical water content at which the rate of evaporation starts to decrease with increase in the duration of evaporation. Surface crack development in soils with different acid concentrations can be divided into three stages: initial cracking, crack development, and crack stabilization. When the acid concentration is higher than 0.4 mol/L, the initial cracking and stabilization stages disappear, and cracks continue to develop until they become stable.

Fractures caused by mining are the main form of water inrush disaster. However, the temporal and spatial development characteristics of fractures of the rock mass due to mining are not clearly understood at present. In this paper, two geometric parameters, namely, fractal dimension and fracture entropy, are proposed to determine the spatial and temporal states of rock mass fractures caused by mining. The spatial and temporal structure characteristics of fractures in the rock mass due to mining are simulated with physical scale model testing based on digital image processing technology. A spatiotemporal model is created to examine the spatial and temporal patterns of hot and cold spots of the fractures based on a Geographic Information System (GIS). Results indicate that the fractal dimensions and entropy of the fractures network in the rock mass increase and decrease with the progression of mining, respectively, which can be examined in three stages. When the fractal dimension of the fractures in rock mass rapidly increases, the conductive fracture zone has a saddle shape. The fracture entropy of fracture has periodic characteristics in the advancing direction of the panel, which reflects the characteristics of periodic weighting. The fractal dimension and fracture entropy of fractures of the rock mass increase with time, and the rock mass system undergoes a process of increasing entropy. When the fractal dimension and fracture entropy of the fractures increase, the spatiotemporal state of fractures in rock mass caused by mining is initiated. When the fractal dimension and fracture entropy of the fractures decrease, the spatiotemporal state of fractures in rock mass is closed.

Background/Aims: We have reported the neuroprotective properties of Heat shock protein B8(HSPB8) against oxygen-glucose deprivation/reoxygenation (OGD/R)-induced injury by inhibiting the mitochondrial apoptotic pathway. However, the exact underlying mechanism of its protective effect on mitochondrial function remains unknown. Here we examined whether the beneficial effect of HSPB8 on OGD/R-induced cell death is associated with mitophagy in mouse neuroblastoma Neuro2a (N2a) cells. Methods: Using the mouse transient middle cerebral artery occlusion (tMCAO) model and mouse neuroblastoma Neuro2a (N2a) cell cultures subjected to OGD/R, we employed western-blot, RT-PCR and immunostaining to analyze the change of expression pattern of HSPB8 and mitophagic flux after brain I/R both in vivo and in vitro. Moreover, via overexpressing HSPB8 or knocking down HSPB8 expression with siRNA in N2a cell, we evaluated the effect of HSPB8 on mitochondrial function during OGD/R. The impact of HSPB8 on mitophagic pathway was also assessed. Finally, mitotophagy inhibitors (CQ and Mdivi-1) were adopted to verify the involvement of mitophagy in HSPB8- induced neuroprotection. Results: HSPB8 could be up-regulated by brain I/R both in vivo and in vitro. Mitophagy enhancement coincided with induction of HSPB8 during I/R. Overexpression of HSPB8 reinforced I/R-induced mitophagy in OGD/R-treated mouse N2a cells and HSPB8 silence suppressed mitophagy process. Inhibition of mitophagy compromised neuroprotection conferred by HSPB8 overexpression. Conclusions: HSPB8 promoted OGD/R-induced mitophagy, which restored the mitochondrial function and contributed to the decrease in cell apoptosis after OGD/R. Therefore, HSPB8 could be a favorable neuroprotective agent for cerebral I/R related disorders.

Abstract Epigenetics defines the persistent modifications of gene expression in a manner that does not involve the corresponding alterations in DNA sequences. It includes modifications of DNA nucleotides, nucleosomal remodeling, and post-translational modifications (PTMs). It is becoming evident that PTMs which act singly or in combination to form “histone codes” orchestrate the chromatin structure and dynamic functions. PTMs of histone tails have been demonstrated to influence numerous biological developments, as well as disease onset and progression. Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating and neurodegenerative disease of the central nervous system, of which the precise pathophysiological mechanisms remain to be fully elucidated. There is a wealth of emerging evidence that epigenetic modifications may confer risk for MS, which provides new insights into MS. Histone PTMs, one of the key events that regulate gene activation, seem to play a prominent role in the epigenetic mechanism of MS. In this review, we summarize recent studies in our understanding of the epigenetic language encompassing histone, with special emphasis on histone acetylation and histone lysine methylation, two of the best characterized histone modifications. We also discuss how the current studies address histone acetylation and histone lysine methylation influencing pathophysiology of MS and how future studies could be designed to establish optimized therapeutic strategies for MS.

HSPB6(Heat shock protein B6), is also referred to as P20/HSP20. Unlike other many other members of sHSP(small Heat shock protein) family, which tend to form high-molecular-mass oligomers, in solution, human HSPB6 only forms dimers. However, it still exhibits chaperon-like activity comparable with that of HSPB5. It is expressed ubiquitously, with high and constitutive expression in muscular tissues. sHSPs characteristically function as molecular chaperones and HSPB6 also has a molecular chaperone activity. HSPB6 is up-regulated in response to diverse cellular stress or damage and protect cells from otherwise lethal conditions. HSPB6 is widely recognized as a principle mediator of cardioprotective signaling and recent studies have unraveled the protective role of HSPB6 in disease or injury to the central nervous system. Moreover, accumulating evidence has implicated HSPB6 as a key mediator of diverse vital physiological processes, such as smooth muscle relaxation, platelet aggregation. The versatility of HSPB6 can be explained by its direct involvement in regulating different client proteins and its ability to form heterooligomer with other sHSPs, which seems to be dependent on HSPB6 phosphorylation. This review focuses on the properties including expression and regulation pattern, phosphorylation, chaperon activity, multiple cellular targets of HSPB6, as well as its possible role in physical and pathological conditions.