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An ophthalmic solution of naringenin (NAR) based on dipotassium glycyrrhizinate (DG) micelle solubilization, called DG-NAR, was prepared, and its effect on dry eye disease (DED) was evaluated. DG-NAR was a clear, colorless aqueous solution with small micelle size (24.75±0.52 nm), narrow size distribution of polydispersity index 0.273±0.160, and a high entrapment efficiency (99.67±0.51%). The solution also revealed good storage stability in a 12-week short-term storage evaluation; it also displayed good vivo ocular tolerance in rabbit eyes investigated via a slit lamp observation and histopathological examination. When observed under fluorescence microscopy, the solution further exhibited improved in vivo corneal permeation profiles in mice eyes. As expected, in a BAC-induced DED mouse model, ocular topical administration of DG-NAR achieved a remarkable efficacy against dry eye symptoms when compared to the DGNAR physical mixture solution or free NAR solution; this included decreased rose bengal and fluorescein staining, increased tear volume and corneal sensitivities, alleviated histopathological symptoms, and reversed corneal epithelium and endothelium damages. Additionally, performance in some efficacy evaluation parameters were better than in the commercialized 0.1% hyaluronic acid sodium salt eye drops. This therapeutic effect can be attributed to the mechanisms regulating HMGB1 signaling and its related proinflammatory cytokines. Together, these in vitro/in vivo results suggested that this novel phytochemical-based nanoformulation of DG-NAR may be a promising candidate in the efficacious treatment of DED.

Black soil areas are strongly affected by rill erosion due to the geomorphic characteristics of flood plains and heavy rainfall. To study the problem of rill erosion in black soil areas and achieve ecological restoration, based on the method of artificially simulated rainfall, the effects of rainfall intensity and slope on the characteristics of flow and sand production on the slope surface of black soil areas were studied, and the erosion pattern of the slope surface after rainfall was monitored by a 3D laser scanner to analyze the erosion of the soil on the slope surface. The slope erosion model was constructed on the basis of the cellular automata (CA) method, and the results of the model’s operation were compared with actual rainfall measurement results to deepen research on the slope erosion mechanism in black soil areas. By analyzing the slope erosion pattern after rainfall, it was found that the surface area and erosion volume of serious slope erosion areas increased with increases in slope gradient. Based on the physical model test results combined with the CA model to simulate flow and sand production on bare slopes under different rainfall intensities, comparison showed that the CA model can accurately simulate flow and sand production on a slope where the Ens coefficient of the flow production rate is between 0.70 and 0.97, thus theoretically verifying the reliability of the model, and on this basis, the erosion pattern of the slope after rainfall was predicted to explore the evolution and development law of erosion.

The magnetic configuration of crystalline solids can have a profound impact on material properties, ranging from subtle structural effects to macroscopic phenomena. With the increased adoption of magnetic crystals for advanced applications, there is a significant need for tools that can characterize and predict the nature of magnetic ordering in solids. While there certainly exist techniques for acquiring such insight, those methods can be plagued by constraints (such as requiring certain elements), ultimately limiting their utility. Here, the strong-dependence of low-frequency (terahertz) vibrational dynamics on weak and long-range forces in crystals is leveraged to determine the spin state of iron phosphate -- a promising material for cathodes in lithium ion batteries. We highlight how terahertz time-domain spectroscopy -- coupled with quantum mechanical simulations -- can discern between various spin configurations in FePO4. Furthermore, the results of this work unambiguously show that the well-accepted space group symmetry for FePO4 is actually incorrect, and that low-frequency spectroscopic measurements provide a clearer picture of the correct structure over the gold-standard of X-ray diffraction. This work opens the door for characterizing, predicting, and interpreting crystalline magnetic ordering using low-frequency vibrational spectroscopy

Acute pancreatitis (AP) is a severe inflammatory disorder hampered by a lack of effective drugs in its clinical practice. Empagliflozin (EMP) exhibits potential effects against AP but is limited by poor water-solubility and low bioavailability. Herein, a novel self-nanomicellizing formulation of EMP with phytochemical rebaudioside A (RA) as the nanocarrier (RA-EMP) was fabricated to address these issues. RA-EMP powder could be simply prepared and exhibited excellent storage stability, dramatically improved EMP's apparent solubility, and instantly self-assembled into micelles with high EMP encapsulation efficiency in water. In vivo experimental studies showed that RA-EMP exhibited significantly enhanced oral bioavailability of EMP and dramatically improved therapeutic efficacy against AP. The mechanisms through suppressing the effects of oxidative stress and proinflammatory cytokines were involved in this therapeutic effect. The results demonstrated that RA-EMP could serve as a promising way to enhance the oral bioavailability and strengthen the potential therapeutic efficacy of EMP against AP.

Maternal obesity is associated with placental oxidative stress. However, the mechanism underlying this association remains poorly understood. In the present study, a gilt obesity model was developed by exposure to different energy diets and used to investigate the role of NADPH oxidase 2 (Nox2) in the placenta. Specifically, 99 gilts (Guangdong Small-ear Spotted pig) at day 60 of gestation were randomly assigned to one of the following three treatments: low-energy group (L, DE=11.50 MJ/kg), medium-energy group (M, DE=12.41 MJ/kg), and high-energy group (H, DE=13.42 MJ/kg), with 11 replicate pens per treatment and 3 gilts per pen. At the start of the study, maternal body weight and backfat thickness were not significantly different in the three treatments. After the study, data indicated that the H group had higher body weight and backfat thickness gain for gilts during gestation and lower piglet birth weight compared with the other two groups. Additionally, the H group showed glucolipid metabolic disorders and increased triglyceride and nonesterified fatty acid contents in the placenta of gilts. Compared with the L group, the H group exhibited lower mitochondrial biogenesis and increased oxidative damage in the placenta. Importantly, increased mRNA expression and protein abundance of Nox2 were observed for the first time in H group placentae. Furthermore, compared with the L group, the H group showed a decrease in the density of placental vessels and the protein levels of vascular endothelial cadherin (VE-cadherin), vascular endothelial growth factor A (VEGF-A), and phosphorylation of vascular endothelial growth factor receptor 2 (p-VEGFR2) as well as the immunostaining intensity of platelet endothelial cell adhesion molecule-1 (CD31). Our findings suggest that maternal high-energy diet-induced obesity increases placental oxidative stress and decreases placental angiogenesis possibly through the upregulation of Nox2.

Summary: Insulin-stimulated hepatic glycogen synthesis is central to glucose homeostasis. Here, we show that PPP1R3G, a regulatory subunit of protein phosphatase 1 (PP1), is directly phosphorylated by AKT. PPP1R3G phosphorylation fluctuates with fasting-refeeding cycle and is required for insulin-stimulated dephosphorylation, i.e., activation of glycogen synthase (GS) in hepatocytes. In this study, we demonstrate that knockdown of PPP1R3G significantly inhibits insulin response. The introduction of wild-type PPP1R3G, and not phosphorylation-defective mutants, increases hepatic glycogen deposition, blood glucose clearance, and insulin sensitivity in vivo. Mechanistically, phosphorylated PPP1R3G displays increased binding for, and promotes dephosphorylation of, phospho-GS. Furthermore, PPP1R3B, another regulatory subunit of PP1, binds to the dephosphorylated GS, thereby relaying insulin stimulation to hepatic glycogen deposition. Importantly, this PP1-mediated signaling cascade is independent of GSK3. Therefore, we reveal a regulatory axis consisting of insulin/AKT/PPP1R3G/PPP1R3B that operates in parallel to the GSK3-dependent pathway, controlling glycogen synthesis and glucose homeostasis in insulin signaling. : Compelling evidence suggests that a GSK3-independent pathway exists, linking insulin signaling with glycogen synthesis. However, the molecular mechanism underlying this pathway remains unclear. Li et al. reveal the presence of an axis for insulin signaling consisting of insulin/AKT/PPP1R3G/PPP1R3B that controls glycogen synthesis and glucose homeostasis in parallel to the GSK3-dependent pathway.

Previous studies have shown that the composition and function of gut microbiota possibly contribute to the oxidative stress and host metabolism of sows. However, a functional link between gut bacteria with oxidative stress and stillbirth rate of sows remain unclear. To address this issue, the reproductive performance, oxidative stress and gut microbiota of sows with high (H) and low (L) stillbirth rate were analyzed. Results showed that, compared with the H group, the L group had a shorter farrowing duration as well as higher concentration of serum total antioxidant capacity and hydroxyl radical scavenging capacity. For the gut microbiota composition of the tested sows, 6 genera differed between the two groups, 7 genera were correlative with stillbirth rate, and 2 genera were correlated with farrowing duration. The relative abundance of Lachnospiraceae_UCG-001, Marvinbryantia and Ruminococcaceae_UCG-004 were negatively correlated with antioxidant capacity, but positively correlated with the stillbirth rate of sows. Furthermore, the microbiota functions in the polyketide sugar unit biosynthesis and nitrotoluene degradation were found to be different between the two groups through the phylotypic investigation of communities by reconstruction of unobserved states. Collectively, gut microbiota and their functions vary between sows with high or low stillbirth rate, while stillbirth rate and farrowing duration are significantly correlated with the gut microbiota composition and oxidative stress status of sows.

This paper presents an accurate and effective method, namely, the improved artificial tree algorithm based on the Green’s kernel function method (IAT-GKFM), to identify the load in time domain. The forward problem of load identification is constructed by using the Green’s kernel function method. The forward problem is discretized using the time domain Galerkin method, where a matrix form for load identification is formed. The IAT algorithm is proposed to solve the inverse multi-dimensions problem in the inverse stage, which aims to minimize the measuring dispersion between the calculated response and the actual response. Several numerical examples are conducted. It is demonstrated that the IAT with high performance can provide more optimum results than those of other compared algorithms. Using this optimized strategy, the loads acting on a simple plate and a vehicle roof are reconstructed successfully. The superiority of IAT-GKFM may motivate the improvement of the other inverse problems.

Five flexible chain & rigid skeleton complementation polycarbazole networks P-Fo, PBT-C1 (C2, C4, C6) were designed and synthesized for gas storage. Increasing the length of alkyl groups from naked to –CH3 to –n-C6H12, the morphology (SEM) and thermostability (TGA) got tremendous changes. PBT-C1 exhibited Brunauer-Emmett-Teller (BET) specific surface area of 685 m2 g−1, which is larger than network P-Fo without TTF substitutions. Nevertheless, further replacing the alkyl-substituted TTF motifs with longer alkyl chains (PBT-C2, C4, C6) would bring a dramatic drop of BET surface areas to less than 100 m2 g−1, similar trends have found for H2, CO2, and CH4 adsorption as side chains changed. It need to be mention that decorating the alkyl group, CH4 adsorption enthalpy can be significantly improved to 52.1 kJ mol−1 (PBT-C4) at zero loading, indicating that alkyl segment can promote the adsorption potential between microporous and CH4 molecule, while have futile effect on H2 and CO2 molecule. These results demonstrated that rational flexible chain grafted into the rigid skeleton at one hand can block the microporous, but it will also have more beneficial on the BET surface areas, pore volume and gas adsorption ability, especially for methane.

The fishbone model is a simplified numerical model for moment-resisting frames that is capable of modelling the effects of column-beam strength and stiffness ratios. The applicability of the fishbone model in simulating the seismic responses of reinforced concrete moment-resisting frames of different sets of column-beam strength and stiffness ratios are evaluated through nonlinear static, dynamic and incremental dynamic analysis on six prototype buildings of 4-, 8- and 12-stories. The results show that the fishbone model is practically accurate enough for reinforced concrete frames, although the assumption of equal joint rotation does not hold in all cases. In addition to the ground motion characteristics and the number of stories in the structures, the accuracy of the model also varies with the column-beam stiffness and strength ratios. The model performs better for strong column-weak beam frames, in which the lateral drift patterns are better controlled by the continuous stiffness provided by the strong columns. When the inelastic deformation is large, the accuracy of the model may be subjected to large record-to-record variability. This is especially the case for frames of weak columns.

A coupled inductor can optimize the weight of a DC/DC converter while the performance characteristics are complicated. To reduce the influence of system fault and keep the stable operation of the coupled converter, a fault-tolerant strategy is proposed. Firstly, a mathematic model is obtained to compare the difference between a coupled converter and a normal converter. Then, an open-circuit fault process is analyzed for fault detection. To design a proper fault-tolerant control system, transfer functions in asymmetric conditions are analyzed, and the operation of the mode switching is optimized for better a transition process. Finally, the method is verified by simulation and experiment.

There have been limited studies on the hardening of cement containing different heavy metals owing to differences in solidification effect. The leachability, setting time, and compressive strength of sulfoaluminate cement (CSA) and ordinary Portland cement (OPC) mixed with different concentrations of Cr(NO3)·9H2O, Pb(NO3)2, Cd(NO3)2·4H2O solution were studied and the hydration products were analyzed using XRD and SEM. The results suggest that CSA immobilized Pb2+ and Cd2+ efficiently, while OPC solidified Cr3+ and Cd2+ well. Cd2+ prolonged the setting time of CSA and Pb2+ remarkably delayed that of OPC. There was only a slight influence of Cr3+, Pb2+, and Cd2+ on the compressive strength of CSA or OPC.

Background Although the genetic spectrum of human colorectal cancer (CRC) is mainly characterized by APC, KRAS and TP53 mutations, driver genes in tumor initiation have not been conclusively demonstrated. In this study, we aimed to identify novel markers for CRC. Methods We performed exome analysis of sporadic colorectal cancer (sCRC) coding regions to screen loss of function (LoF) mutation genes, and carried out systems-level approaches to confirm top rank gene in this study. Results We identified loss of BMP5 is an early event in CRC. Deep sequencing identified BMP5 was mutated in 7.7% (8/104) of sCRC samples, with 37.5% truncating mutation frequency. Notably, BMP5 negative expression and its prognostic value is uniquely significant in sCRC but not in other tumor types. Furthermore, BMP5 expression was positively correlated with E-cadherin in CRC patients and its dysregulation play a vital role in epithelial-mesenchymal transition (EMT), thus triggering tumor initiation and development. RNA sequencing identified, independent of BMP/Smads pathway, BMP5 signaled though Jak-Stat pathways to inhibit the activation of oncogene EPSTI1. Conclusions Our result support a novel concept that the importance of BMP5 in sCRC. The tumor suppressor role of BMP5 highlights its crucial role in CRC initiation and development. Electronic supplementary material The online version of this article (10.1186/s12943-018-0925-7) contains supplementary material, which is available to authorized users.

NORFA, the first lincRNA associated with sow fertility, has been shown to control granulosa cell (GC) functions and follicular atresia. However, the underlying mechanism is not fully understood. In this study, RNA-seq was performed and we noticed that inhibition of NORFA led to dramatic transcriptomic alterations in porcine GCs. A total of 1,272 differentially expressed transcripts were identified, including 1167 DEmRNAs and 105 DEmiRNAs. Furthermore, protein–protein interaction, gene-pathway function, and TF–miRNA–mRNA regulatory networks were established and yielded four regulatory modules with multiple hub genes, such as AR, ATG5, BAK1, CENPE, NR5A1, NFIX, WNT5B, ssc-miR-27b, and ssc-miR-126. Functional assessment showed that these hub DEGs were mainly enriched in TGF-β, PI3K-Akt, FoxO, Wnt, MAPK, and ubiquitin pathways that are essential for GC states (apoptosis and proliferation) and functions (hormone secretion). In vitro, we also found that knockdown of NORFA in porcine GCs significantly induced cell apoptosis, impaired cell viability, and suppressed 17β-estradiol (E2) synthesis. Notably, four candidate genes for sow reproductive traits (INHBA, NCOA1, TGFβ-1, and TGFBR2) were also identified as potential targets of NORFA. These findings present a panoramic view of the transcriptome in NORFA-reduced GCs, highlighting that NORFA, a candidate lincRNA for sow fertility, is crucial for the normal states and functions of GCs.

In order to prevent reflection cracking of composite pavement, the Hills formula, Goodman hypothesis, and ABAQUS software are used to carry out simultaneous dynamic modulus tests on composite pavement specimens. The temperature shrinkage stress formula for an asphalt surface considering stress relaxation is derived. The change rule for the accumulated temperature shrinkage stress of an asphalt surface layer with varying cooling range and cooling rate is obtained. The influences of different asphalt and concrete layer thicknesses on the temperature shrinkage stress at the asphalt layer bottom joint are obtained considering the influence of concrete shrinkage on the temperature stress at the asphalt layer bottom joint.

In order to study what the effect of superplasticizers on the setting time, fluidity and compressive strength of calcium sulfoaluminate cement (CSA) a naphthalene-based superplasticizer (BNS) and a polycarboxylic acid superplasticizer (PC) were selected to interact with CSA pastes and ye’elimite, respectively. X-ray diffraction (XRD), thermogravimetric (TG) analysis and scanning electron microscopy (SEM) analytical methods were used to investigate the class, amount and microstructure of the CSA pastes and ye’elimite pastes hydration products under the effect of the superplasticizers. The results showed that the addition of BNS can promote ettringite generation and thus improve the early compressive strength. As the addition of BNS increased from 0.8 wt% to 2.0 wt%, the initial setting time was prolonged 10 min, the final setting time was prolonged 7 min, the 5 min fluidity was improved from no fluidity to 220 mm. However, as the addition of PC increased from 0.08 wt% to 0.20 wt%, the setting time of the PC just changed within 3 min, the 5 min fluidity increased from 110 mm to 195 mm and no 15 min fluidity at all was observed. AS seen by SEM, it can be stated that generated ettringite under the addition of PC was layered and lacking bonding, and its morphology changed from rod-like to flake-like, leading to a decrease in early compressive strength.

With the rapid development of deep learning and wireless communication technology, emotion recognition has received more and more attention from researchers. Computers can only be truly intelligent when they have human emotions, and emotion recognition is its primary consideration. This paper proposes a multimodal emotion recognition model based on a multiobjective optimization algorithm. The model combines voice information and facial information and can optimize the accuracy and uniformity of recognition at the same time. The speech modal is based on an improved deep convolutional neural network (DCNN); the video image modal is based on an improved deep separation convolution network (DSCNN). After single mode recognition, a multiobjective optimization algorithm is used to fuse the two modalities at the decision level. The experimental results show that the proposed model has a large improvement in each evaluation index, and the accuracy of emotion recognition is 2.88% higher than that of the ISMS_ALA model. The results show that the multiobjective optimization algorithm can effectively improve the performance of the multimodal emotion recognition model.

Preparing activated carbon with high volumetric performance in organic electrolyte is crucial for developing high-energy and miniaturized supercapacitors, but still challenging because high surface area and large pore size are required to effectively store large-sized organic electrolyte ions, which usually result in the low density. Herein, an ultrafast strategy is proposed to tailor the interconnected porous structure of activated carbon through introducing CO2 at the end of homogeneous activation. The uniformly distributed potassium components in carbon matrix promote a robust catalytic etching by CO2, leading to precise tailoring of the ultramicropores (0.50-0.72 nm) to large micropores (0.81-1.14 nm) within only two minutes. The optimized sample with both high surface area and compaction density (2147 m2 g-1, 0.68 g cm-3) shows high gravimetric and volumetric capacitances (155 F g-1 and 106 F cm-3 at 1 A g-1) as well as good rate performance (102 F g-1 and 70 F cm-3 at 20 A g-1) in organic electrolyte. The symmetric supercapacitor achieves high energy densities of 35 Wh kg-1 and 24 Wh L-1 at 573 W kg-1 and 395 W L-1, respectively, indicating great potential of the ultrafast tailoring strategy for practical application.

The high moisture content of lignite raw materials leads to its low combustion efficiency and large CO 2 emissions. Therefore, the drying of lignite are the keys to achieving efficient and clean utilization, and further realizing energy-saving and emission-reduction. In this study, based on coupling centrifugal effect of high-speed self-rotation and revolution of particles in cyclone, low-energy consumption and high-efficiency lignite cyclone rotational drying was realized at a low carrier gas temperature (lower than 100°C) and in a short residence time (less than 10 s). The influence of operating parameters and structure parameters on lignite drying efficiency were investigated, when carrier gas temperature was 80 °C, the moisture content of lignite can be reduced from 45.1% to 15.2% after single-stage cyclone drying in a 75 mm diameter cyclone. When the diameter of the cyclone was expanded to 100 mm, the single-stage dehydration efficiency can be increased to 75.8%. Compared with the fixed-bed evaporative drying, the cyclone rotational drying can increase the drying rate and reduce the drying time and energy consumption. It is revealed that the cyclone rotational drying method provides a new idea for the lignite drying technology, and can serve as guidance for industrial applications.

The efficacy of PD-1/PD-L1 blockades is heterogeneous in different molecular subtypes of gastric cancer (GC). In this study, we analyzed relevant clinical trials to identify the molecular subtypes associated with the efficacy of PD-1/PD-L1 blockades, and public datasets, patient samples, and GC cell lines were used for investigating potential mechanisms. We found that GC with EBV-positive, MSI-H/dMMR, TMB-H or PIK3CA mutant subtype had enhanced efficacy of PD-L1/PD-1 blockades. Also, differentially expressed genes of these molecular subtypes shared the same gene signature and functional annotations related to immunity. Meanwhile, CIBERSORT identified that the overlapping landscapes of tumor-infiltrating immune cells in the four molecular subtypes were mainly M1-like macrophages (M1). The relationships between M1 and clinical characteristics, M1, and gene signatures associated with PD-1/PD-L1 blockades also revealed that M1 was associated with improved prognosis and required for the efficacy of PD-L1/PD-1 blockades in GC. We identified that tumor-infiltrating CD68+CD163− macrophages could represent M1 calculated by CIBERSORT in clinical application, and CXCL9, 10, 11/CXCR3 axis was involved in the mechanism of CD68+CD163− macrophages in the enhanced efficacy of PD-L1/PD-1 blockades. In conclusion, CD68+CD163− macrophages are required for the efficacy of PD-L1/PD-1 blockades and expand the applicable candidates in GC patients without the molecular subtypes.

Hesperetin (HSP) has excellent biological activities with poor water solubility which limits its clinical development. In this study, we successfully prepared a novel, self-assembled micelle based on Rebaudioside A (RA) for oral delivery of HSP with improved bioavailability and therapeutic effects. We found that RA and HSP could be formylated into nanomicelles with particle sizes of 4.541 nm ± 0.048 nm. HSP was readily encapsulated into RA micelles and this improved its water solubility (to 12.74 mg/mL ± 0.28 mg/mL). The MTT results showed that RA-HSP enhanced the cytotoxicity, the clonal formation inhibitory activity, and cell migration inhibitory activity of HSP in human breast cancer MDA-MB-231 cells. The mechanism results showed that RA-HSP induced cell apoptosis by inducing the production of reactive oxygen species (ROS), destroying the mitochondrial membrane potential (MMP), and inhibiting the PI3K/Akt signaling pathway. Moreover, RA-HSP enhanced the anticancer activity, increased the oral bioavailability and tissue distribution of HSP in vivo. Moreover, the mechanism studies in vivo found that HSP inhibited PI3K/Akt signaling pathway with low side effects. These findings indicate that RA micelle formulations have great potential in oral drug delivery systems for the delivery of hydrophobic drugs.

A spherical cellulose adsorbent embedded with black wattle extract (SABW) was prepared by an inverse suspension method, and used to adsorb the typical food pigment, gardenia yellow pigment (GYP). Results of SEM, XRD, FTIR and BET characterization showed that SABW was composed of abundant porous structures and functional groups such as -C[double bond, length as m-dash]O, -OH and benzene ring groups. The batch adsorption experiments revealed that SABW presented excellent adsorption performance for GYP with a high adsorption percentage of 97.96%. The adsorption process followed the Langmuir and Freundlich adsorption isotherm, and the experimental data were in good agreement with the pseudo-second order dynamic model. Furthermore, the main adsorption mechanism involved hydrogen bonding, electrostatic interaction and pore adsorption. Importantly, the desorption and regeneration experiments showed that SABW had satisfactory reusability and retained 92.30% adsorption after 4 cycles. The above results provide a vital theoretical basis for the extraction of GYP.

The treatment of large established tumors remains a significant challenge and is generally hampered by poor drug penetration and intrinsic drug resistance of tumor cells in the central tumor region. In the present study, we developed bacterial particles (BactPs) to deliver chemotherapeutics into the tumor mass by hijacking neutrophils as natural cell-based carriers. BactPs loaded with doxorubicin, 5-fluorosuracil, or paclitaxel induced significantly greater tumor regression than unconjugated drugs. This effect was mediated by the ability of BactPs to incorporate chemotherapeutics and serve as vascular disrupting agents that trigger innate host responses and recruit phagocytic neutrophils. Vascular disruption resulted in extensive cell death in the central areas of the tumor mass. Recruited neutrophils acted as natural cellular carriers to deliver engulfed BactPs, which ensured drug delivery into the tumor mass and cytotoxic effects in areas that are normally inaccessible to traditional chemotherapy. Thus, BactPs eradicate large established tumors by functioning as vascular disrupters and natural drug carriers for neutrophil-mediated chemotherapy.

To formulate a xanthan gum–containing linezolid ophthalmic solution (LZD-XG) as a new antibiotic treatment against ocular bacterial infection. LZD-XG was prepared and evaluated for its in vitro/in vivo ocular tolerance, in vitro/in vivo antibacterial activity, and in vivo ocular penetration. The optimized LZD-XG exhibited good in vitro/in vivo eye tolerance. A prolonged ocular surface residence time of LZD-XG was observed after topical instillation, and the ocular permeation was significantly better for LZD-XG than fora linezolid (LZD) ophthalmic solution. The in vitro antimicrobial activity was significantly better with LZD-XG than with LZD. In vivo evaluation also confirmed a strong therapeutic treatment effect of LZD-XG, as it significantly improved the clinical symptoms, ameliorated the damage of Staphylococcus aureus to ocular tissues, lowered the colony forming unit counts in the cornea, and decreased the myeloperoxidase activity in the cornea. LZD-XG was deemed a viable ophthalmic solution against ocular bacterial infection due to its excellent in vitro and in vivo characterizations.

NORFA, the first lincRNA associated with sow fertility, has been shown to control granulosa cell (GC) functions and follicular atresia. However, the underlying mechanism is not fully understood. In this study, RNA-seq was performed and we noticed that inhibition of NORFA led to dramatic transcriptomic alterations in porcine GCs. A total of 1,272 differentially expressed transcripts were identified, including 1167 DEmRNAs and 105 DEmiRNAs. Furthermore, protein–protein interaction, gene-pathway function, and TF–miRNA–mRNA regulatory networks were established and yielded four regulatory modules with multiple hub genes, such as AR, ATG5, BAK1, CENPE, NR5A1, NFIX, WNT5B, ssc-miR-27b, and ssc-miR-126. Functional assessment showed that these hub DEGs were mainly enriched in TGF-β, PI3K-Akt, FoxO, Wnt, MAPK, and ubiquitin pathways that are essential for GC states (apoptosis and proliferation) and functions (hormone secretion). In vitro, we also found that knockdown of NORFA in porcine GCs significantly induced cell apoptosis, impaired cell viability, and suppressed 17β-estradiol (E2) synthesis. Notably, four candidate genes for sow reproductive traits (INHBA, NCOA1, TGFβ-1, and TGFBR2) were also identified as potential targets of NORFA. These findings present a panoramic view of the transcriptome in NORFA-reduced GCs, highlighting that NORFA, a candidate lincRNA for sow fertility, is crucial for the normal states and functions of GCs.

Liver cancer is associated with high mortality, particularly in patients infected with the hepatitis B virus. Treatment methods remain very limited. Here, we explored the effects of 17β-estradiol (E2) on apoptosis of various liver cell lines (LO2, HepG2, and HepG2.2.15 cells). Within a certain concentration range, 17β-estradiol induced oxidative stress and apoptosis of HepG2 cells, downregulated ERα-36 expression, and increased Akt and Foxo3a phosphorylation. p-Foxo3a became localized around the nucleus but did not enter the organelle. The levels of mRNAs encoding manganese superoxide dismutase (MnSOD) and catalase, to the promoters of which Foxo3a binds to trigger gene expression, were significantly reduced in HepG2 cells. 17β-estradiol had no obvious effects on LO2 or HepG2.2.15 cells. We speculate that 17β-estradiol may induce oxidative stress in HepG2 cells by increasing Foxo3a phosphorylation, thus promoting apoptosis. This may serve as a new treatment for hepatocellular carcinoma.

Criteria are proposed for determining the stiffness and strength demands for the seismic design of pin-supported walls in low- and medium-rise reinforced-concrete moment frames. A plasticit...

Background: Cancer-associated cachexia is characterized by ongoing loss of skeletal muscle and has a high incidence in gastric cancer. Although studies have focused on the effect of inflammatory cytokines on skeletal muscle loss, it is not clear whether inflammatory cytokines affect other physiological functions, particularly immunity in gastric cancer. Thus, we aim to investigate the relationships between circulating TNF-α, skeletal muscle and peripheral immune status in gastric cancer.Methods: Totally 392 gastric cancer patients in cohort A and 60 gastric cancer patients in cohort B were selected from the prospective cohort study NCT03115931 and ChiCTR1900026578 in West China Hospital, Sichuan University, respectively. Besides, human skeletal muscle myoblasts (HSMMs) and peripheral CD8+ T cells completed about 7 to 9 days successive TNF-α intervention with different concentrations. Results: From data in cohort A, multivariate analysis showed that preoperative weight loss ≥5% was associated with circulating TNF-α (P =0.001) and TNM stage (P =0.002). ROC curve indicated that cut-off point of 9.96 pg/ml for circulating TNF-α was an important warning of weight loss ≥5% in patient with gastric cancer. Before surgery, high circulating TNF-α (≥ 9.96 pg/ml) was associated with significantly lower body weight, skeletal muscle mass and handgrip strength but not fat mass. After radical surgery, high circulating TNF-α was also associated with significantly more loss of body weight and skeletal muscle mass instead of fat mass. In cohort B and vitro experiments, immunohistochemistry, western blot and flow cytometry identified that high TNF-α led to myofiber change, decreased expression of AMP-dependent protein kinase (AMPK) and phosphate-AMPK in skeletal muscle and increased myoblast apoptosis. Flow cytometry found that circulating TNF-α was not correlated with PD-1, LAG-3, TIM-3 and TIGIT expressed on peripheral CD8+ T cells, and TNF-α not only promoted the proliferation of CD8+ T cells but also increased their apoptosis ratio at higher concentration.Conclusions: In our study, we found that TNF-α could result in myofiber change, interfered glycometabolism of skeletal muscle, whereas promoted the proliferation of CD8+ T cells in gastric cancer during cachexia, and preoperative circulating TNF-α of more than 9.96 pg/ml could indicate a high risk of weight loss.

Nimodipine (NMD), a calcium channel blocker, has demonstrated benefits in treating glaucoma. However, its ocular therapeutic application remains limited due to its poor aqueous solubility, which restrains the development of an ophthalmic formulation. Thus, the present study aimed to formulate an NMD micelle ophthalmic solution to enhance the potential of NMD in an ocular topical formulation to treat glaucoma. The NMD micelle ophthalmic solution was formulated with nanocarriers composed of rebaudioside A and D-α-tocopheryl polyethylene glycol 1000 succinate. Spherical mixed micelles were optimized and obtained at a small micelle size 13.429 ± 0.181 nm with a narrow size distribution (polydispersity index 0.166 ± 0.023) and high encapsulation efficiency rate (99.59 ± 0.09%). Compared with free NMD, NMD in micelles had much greater in vitro membrane permeability and antioxidant activity. The NMD micelle ophthalmic solution was well tolerated in rabbit eyes. It profoundly improved the in vivo intraocular permeation of NMD, and in vivo intraocular pressure reduction and improved miosis were also observed. Accordingly, this NMD micelle ophthalmic solution might be a promising ocular formulation to treat glaucoma. Graphical abstract.

Honokiol (HK) has a variety of biological activities, but its poor solubility limits its application. Rebaudioside A (RA) is able to self-assemble into micelles, which can be used for oral delivery of anticancer drugs. This study aims to create and evaluate a nano-sized anticancer drug delivery system based on RA, as RA micelles are thought to strengthen the therapeutic effects of HK. The results showed that RA and HK can be formulated into self-assembling micelles (RA-HK) with a size of 4.356 ± 0.142 nm and uniform distribution (PDI = 0.1906 ± 0.0184). Moreover, RA-HK could enhance the antitumor activity of HK in vitro. Further, it was shown that RA-HK can induce G0/G1 cycle arrest, apoptosis, and reactive oxygen species (ROS) generation in HuH-7 cells. The results for this mechanism indicate that RA-HK can induce DNA damage as well as changes in cycle and apoptotic-related proteins and activate the ERK signaling pathway. The in vivo antitumor results showed that RA-HK could also enhance the antitumor activity of HK in mice and does not induce any side effects. The pharmacokinetic results illustrate that RA-HK can increase the oral bioavailability of HK that and RA-HK is widely distributed in rats. Taken together, the above results prove that RA is a novel oral nano-drug delivery system with great potential for the delivery of hydrophobic antitumor drugs, such as HK.

Drought is among the most destructive abiotic stresses limiting crop growth and yield worldwide. Although most research has focused on the contribution of plant-associated microbial communities to plant growth and disease suppression, far less is known about the microbes involved in drought resistance among desert plants. In the present study, we applied 16S rRNA gene amplicon sequencing to determine the structure of rhizosphere and root endosphere microbiomes of Alhagi sparsifolia Compared to those of the rhizosphere, endosphere microbiomes had lower diversity but contained several taxa with higher relative abundance; many of these taxa were also present in the roots of other desert plants. We isolated a Pseudomonas strain (LTGT-11-2Z) that was prevalent in root endosphere microbiomes of A. sparsifolia and promoted drought resistance during incubation with wheat. Complete genome sequencing of LTGT-11-2Z revealed 1-aminocyclopropane-1-carboxylate deaminases, siderophore, spermidine, and colanic acid biosynthetic genes, as well as type VI secretion system (T6SS) genes, which are likely involved in biofilm formation and plant-microbe interactions. Together, these results indicate that drought-enduring plants harbor bacterial endophytes favorable to plant drought resistance, and they suggest that novel endophytic bacterial taxa and gene resources may be discovered among these desert plants.IMPORTANCE Understanding microbe-mediated plant resistance to drought is important for sustainable agriculture. We performed 16S rRNA gene amplicon sequencing and culture-dependent functional analyses of Alhagi sparsifolia rhizosphere and root endosphere microbiomes and identified key endophytic bacterial taxa and their genes facilitating drought resistance in wheat. This study improves our understanding of plant drought resistance and provides new avenues for drought resistance improvement in crop plants under field conditions.

Tea saponin (TS), a plant derived biosurfactant, was used to investigate on its effectiveness on the extraction of three typically selected rare earth elements (REEs, light lanthanum (La), medium arrowhead (Dy) and heavy erbium (Er)) from contaminated soils, in the presence of important toxic heavy metals (lead (Pb) and cadmium (Cd)). A complete procedure, involving the extraction of REEs in soils, the recovery of REEs and TS in the extraction leachates and the reuse of the recovered TS, was established. Experimental results showed that the optimal extraction parameters were consumption of 1.2 g/g (TS/soil), pH of 5 and the extraction time of 24 h. The recovery efficiencies of La, Dy, Er, Cd and Pb achieved 96.9%, 88%, 84.3%, 88% and 91.1% using 0.3 g/g (Ca(OH)2/soil). The overall extraction efficiencies of La, Dy, Er, Cd and Pb were 53.9%, 73.2%, 71.7%, 95.9% and 38.8% by three times using the recovered TS solution. The extractable fractions of La, Dy, Er, Cd and Pb in soil were found to be highest in their acid soluble and reducible forms. Mechanisms studies indicated the increased binding strength (IR) and the decreased mobility (MF) of REEs and metals after the flushing with TS. Carboxyl groups in TS were attributed to the formation of complexation and agglomeration between TS and studied REEs and other metals, confirmed by the analysis of both the X-ray photoelectron spectroscopy (XPS) and the dynamic light scattering (DLS). This study established an environmentally-friendly contaminated soil remediation and the recovery of valuable REEs by the combination use of TS and calcium hydroxide.

This study aims to create and evaluate a kaempferol (KAE) ophthalmic solution based on polyvinylpyrrolidone (PVP) nanocomplexes. KAE can be highly complexed with PVP K-17PF (17PF) to formulate an aqueous ophthalmic solution named 17PF-KAE. The optimized 17PF-KAE displays high complexing efficiency, an ultra-small size (8.628 ± 0.066 nm), and good aqueous dispersibility. 17PF-KAE did not show any obvious cytotoxicity or in vivo ocular tissue toxicity. Further, 17PF-KAE was observed to facilitate significant improvement in in vitro parallel artificial membrane permeability, in vitro cellular uptake, and ex vivo corneal permeation of KAE. Regarding the in vivo ocular absorption test, the KAE levels in the cornea and aqueous humor determined from the 17PF-KAE group were much higher than those in the free KAE solution group in addition to conjunctiva and the iris-ciliary body at certain time points. 17PF-KAE was also observed to promote remarkable improvement in in vitro antioxidant activity and in vivo anti-inflammatory activity. Moreover, a topical 17PF-KAE solution in mice eyes showed significant improvement in the treatment efficacy of corneal alkali burns over the free KAE solution. The therapeutic mechanism was also associated with inhibiting the production of key mediators of inflammation (CD54, IL-6, and TGF-β1) and angiogenic factors (VEGF). Therefore, these results demonstrate that 17PF-KAE may be a promising new ophthalmic formulation for the prophylaxis and treatment of oxidative stress and inflammation-related ocular diseases.

Pavement performance prediction is a crucial issue in big data maintenance. This paper develops a hybrid grey relation analysis (GRA) and support vector machine regression (SVR) technique to predict pavement performance. The prediction model can solve the shortcomings of the traditional model including a single consideration factor, a short prediction period, and easy overfitting. GAR is employed in selecting the main factors affecting the performance of asphalt pavement. The SVR is performed to predict the performance. Finally, the data collected from the weather station installed on Guangyun Expressway were adopted to verify the validity of the GRA-SVR model. Meanwhile, the contrast with the grey model (GM (1, 1)), genetic algorithm optimization BP[[parms resize(1),pos(50,50),size(200,200),bgcol(156)]]081%, −0.823%, 1.270%, and −4.569%, respectively. The study concluded that the nonlinear and multivariate prediction model established by GRA-SVR has higher precision and operability, which can be used in long-period pavement performance prediction.

Colorectal cancer (CRC) is a leading cause of cancer deaths worldwide. Accumulation of varieties of epigenetic changes, including miRNA regulation, is one of the fundamental processes driving CRC initiation and progression. Mir-92a has been reported in several studies as an oncogene, and particularly in colorectal cancer, it has become a useful biomarker for early detection of CRC in both serum or stool. The Cancer Genome Atlas (TCGA) is a powerful database to analyze cancer-related genes and their correlation with patients' pathological information. However, miR-92a expression and its regulating target genes has yet to be investigated in TCGA system. In this study, we found miR-92a expression is associated with CRC pathological process. Notably, high expression of miR-92a mainly occurs in microsatellite-stable (MSS) cases. Further experiments showed exogenous introduction of miR-92a into LoVo and SW480 cells could enhance cell proliferation, migration, and invasion, whereas inhibition of miR-92a showed the opposite effects. A system analysis based on binding capacity and expression correlation analysis confirmed DKK3 and KLF4 are the top target genes of miR-92a, and novel target SMAD7 highlights the role of miR-92a in BMPs/SMAD pathway. In conclusion, miR-92a acts as an oncomir and directly targets Wnt/β-catenin, PTEN/Akt/FoxO, and BMP/Smads related genes, thus participates in CRC progression.