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To develop aryloxyphenoxypropionate herbicides with novel structure and improved activity, a total of twenty-eight novel quinazolinone–phenoxypropionate derivatives containing a diester moiety were designed and synthesized. The herbicidal bioassay results in the greenhouse showed that QPEP-I-4 exhibited excellent herbicidal activity against E. crusgalli, D. sanguinalis, S. alterniflora, E. indica, and P. alopecuroides with inhibition rates >80% at a dosage of 150 g ha−1 and displayed higher crop safety to G. hirsutum, G. max, and A. hypogaea than the commercial herbicide quizalofop-p-ethyl. Studying the herbicidal mechanism by phenotypic observation, membrane permeability evaluation, and transcriptomic analysis revealed that a growth inhibition of plants by QPPE-I-4 was the result from damage of the plants’ biomembrane. The evaluation of ACCase activity in vivo indicated that QPPE-I-4 could inhibit ACCase and may be a new type of ACCase inhibitor. The present work indicated that QPPE-I-4 could represent a lead compound for further developing novel AOPP herbicides.

Irradiation with ultraviolet A (UVA) plays an important role in the pathogenesis of skin photoaging since it increases oxidative stress and inflammation in the epidermis. There is an urgent need to screen, investigate, and apply the potential anti-photoaging active ingredients. Agaricus blazei Murill (ABM) polysaccharides have a wide range of promising pharmacological applications. Previous studies have confirmed their antioxidant effect, but whether it has an anti-photoaging effect is unclear. In this study, two ABM polysaccharides (AB-J and AB-K) were obtained to discuss the potential photodamage-protective capacity. The free radical scavenging abilities in vitro, the safety assessment, and their protective effects and mechanisms on UVA-induced human fibroblasts (HSFs) were evaluated. The intracellular antioxidant enzyme levels and extracellular matrix proteins, such as COL-I and ELN, were significantly accelerated, and metalloproteinases (MMP-1, and MMP-9) were decreased by AB-J and AB-K. The Keap-1-Nrf2/ARE signaling pathway was activated, thus inducing the upregulated expression of downstream genes (Ho-1 and Nqo-1). The suppression of P38 and Jnk1 by AB-J and AB-K was speculated to be the inducer of the activation of the Keap-1-Nrf2/ARE signaling pathway. Owing to the excellent exhibition of AB-J, its safety assessment and the structural characterization are discussed further.

ABSTRACTSchizophyllum commune is a fungus with applications both in medicine and foods, which produces IPS and EPS. However, there is no comparative study on the activity comparison of IPS and EPS and its mechanism of antioxidant effect. In this study, the antioxidant activities of the two polysaccharides were measured in biochemical, cellular and molecular levels, and H2O2 induced oxidative damage model of HSFs was established to explore the protective effects of EPS and IPS. We found IPS and EPS both achieved a good antioxidant effect. They can also improve the cellular levels of SOD and reduce MDA. Insights regarding the molecular mechanism were studied, we found that both EPS and IPS could increase the expression of Nrf2 in Keap1-Nrf2/ARE signaling pathway. At the same time, they could inhibit the expression of the negative feedback gene Keap1 and promote the expression of downstream gene GCLC, Gstt-1, Nqo1 and Ho-1.

UVB radiation is known to induce photodamage to the skin, disrupt the skin barrier, elicit cutaneous inflammation, and accelerate the aging process. Agaricus blazei Murill (ABM) is an edible medicinal and nutritional fungus. One of its constituents, Agaricus blazei Murill polysaccharide (ABP), has been reported to exhibit antioxidant, anti-inflammatory, anti-tumor, and immunomodulatory effects, which suggests potential effects that protect against photodamage. In this study, a UVB-induced photodamage HaCaT model was established to investigate the potential reparative effects of ABP and its two constituents (A1 and A2). Firstly, two purified polysaccharides, A1 and A2, were obtained by DEAE-52 cellulose column chromatography, and their physical properties and chemical structures were studied. A1 and A2 exhibited a network-like microstructure, with molecular weights of 1.5 × 104 Da and 6.5 × 104 Da, respectively. The effects of A1 and A2 on cell proliferation, the mitochondrial membrane potential, and inflammatory factors were also explored. The results show that A1 and A2 significantly promoted cell proliferation, enhanced the mitochondrial membrane potential, suppressed the expression of inflammatory factors interleukin-1β (IL-1β), interleukin-8 (IL-8), interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α), and increased the relative content of filaggrin (FLG) and aquaporin-3 (AQP3). The down-regulated JAK-STAT signaling pathway was found to play a role in the response to photodamage. These findings underscore the potential of ABP to ameliorate UVB-induced skin damage.

Acne is a chronic inflammatory skin disease with a recurring nature that seriously impacts patients’ quality of life. Currently, antibiotic resistance has made it less effective in treating acne. However, Paris polyphylla (P. polyphylla) is a valuable medicinal plant with a wide range of chemical components. Of these, P. polyphylla saponins modulate the effects in vivo and in vitro through antibacterial, anti-inflammatory, immunomodulatory, and antioxidant effects. Acne is primarily associated with inflammatory reactions, abnormal sebum function, micro-ecological disorders, hair follicle hyperkeratosis, and, in some patients, immune function. Therefore, the role of P. polyphylla saponins and their values in treating acne is worthy of investigation. Overall, this review first describes the distribution and characteristics of P. polyphylla and the pathogenesis of acne. Then, the potential mechanisms of P. polyphylla saponins in treating acne are listed in detail (reduction in the inflammatory response, antibacterial action, modulation of immune response and antioxidant effects, etc.). In addition, a brief description of the chemical composition of P. polyphylla saponins and its available extraction methods are described. We hope this review can serve as a quick and detailed reference for future studies on their potential acne treatment.

Abstract Macrophage polarization determines the production of cytokines that fuel the initiation and evolution of rheumatoid arthritis (RA). Thus, modulation of macrophage polarization might represent a potential therapeutic strategy for RA. However, coordinated modulation of macrophages in the synovium and synovial fluid has not been achieved thus far. Herein, we develop a biomimetic ApoA-I mimetic peptide-modified neutrophil membrane-wrapped F127 polymer (R4F-NM@F127) for targeted drug delivery during RA treatment. Due to the high expression of adhesion molecules and chemokine receptors on neutrophils, the neutrophil membrane coating can endow the nanocarrier with synovitis-targeting ability, with subsequent recruitment to the synovial fluid under the chemotactic effects of IL-8. Moreover, R4F peptide modification further endows the nanocarrier with the ability to target the SR-B1 receptor, which is highly expressed on macrophages in the synovium and synovial fluid. Long-term in vivo imaging shows that R4F-NM@F127 preferentially accumulates in inflamed joints and is engulfed by macrophages. After loading of the anti-inflammatory drug celastrol (Cel), R4F-NM@F127-Cel shows a significant reduction in hepatotoxicity, and effectively inhibits synovial inflammation and alleviates joint damage by reprogramming macrophage polarization. Thus, our results highlight the potential of the coordinated targeted modulation of macrophages as a promising therapeutic option for the treatment of RA.

Abstract To study the soil consolidation effect of shrub plant roots on tailings soil and to explore the frictional characteristics of plant roots on tailings soil, three experimental conditions of the root–soil interface were established by using a modified indoor direct shear instrument with binders such as liquid sodium silicate and cyanoacrylate to conduct direct shear frictional tests at the root–soil interface using the roots of the typical slope protection plant Amorpha fruticosa. The Gompertz improved curve model was established by using the relationship between shear stress and shear displacement and the trend of the root–soil interface parameter index. The results were compared between the improved Gompertz curve model and the Clough–Duncan hyperbolic model, and a two-factor coupled improved Gompertz interfacial intrinsic structure model with normal stress and cohesive strength factor was established. The results showed that the interface shear stress and shear displacement showed strain hardening characteristics at different normal pressures for cohesive strength ratios of 1.5 and 1.7 at the root–tailing soil interface. At a cohesive strength ratio of 1.6, strain-softening was observed from 100 to 300 kPa and strain hardening was observed at 400 kPa. The improved Gompertz curve model predicts the shear stress and shear displacement curves at the root–soil interface with different cohesive strengths more reasonably than the Clough–Duncan hyperbolic model, and the maximum accuracy can be improved by nearly 40%. The two-factor coupled improved Gompertz curve model can fit the shear stress versus shear displacement relationship at the A. fruticosa root–tailing soil interface.

The most common form of non-traumatic necrosis of the femoral head is anoxic necrosis of the femoral head, which is a metabolic disease, mainly involving young and middle-aged people. Apoptosis and its related signal regulation pathway play an important role in the occurrence and development of hypoxic necrosis of the femoral head. In order to investigate the possible pathological manifestations of miR-206 and VEGF/PI3K/AKT signal pathway genes and their interactions in hypoxic necrosis of the femoral head, this paper intended to systematically study the expression and regulation mechanism of miR-206 and VEGF/PI3K/AKT signal pathway genes. The interaction between miR-206 and VEGF/PI3K/AKT signaling pathway and its regulation on apoptosis, differentiation and proliferation of human osteoblast cell line hFOB1.19 (SV40 transfer of human osteoblasts) were studied by double luciferase reporter gene analysis, overexpression and inhibition of miR-206, and gene silencing of VEGF/PI3K/AKT signaling pathway. After 24 h and 48 h of intervention with MicroRNA 206 on osteoblasts, it was found that the fluorescence intensity of caspase-3 was higher than that of 0 h group (p < 0.05). This paper has provided an important research basis for the research of femoral head necrosis and the development of new diagnosis and therapeutic drugs for this kind of disease. It also has provided a reference for the further promotion of the chemotherapy drug delivery system.

Hippophae rhamnoides L. has been widely used in research and application for almost two decades. While significant progress was achieved in the examination of its fruits and seeds, the exploration and utilization of its by-products have received relatively less attention. This study aims to address this research gap by investigating the effects and underlying mechanisms of sea buckthorn seed residues both in vitro and in vivo. The primary objective of this study is to assess the potential of the hydroalcoholic extract from sea buckthorn seed residues (HYD-SBSR) to prevent cell apoptosis and mitigate oxidative stress damage. To achieve this, an H2O2-induced B16F10 cell model and a D-galactose-induced mouse model were used. The H2O2-induced oxidative stress model using B16F10 cells was utilized to evaluate the cellular protective and reparative effects of HYD-SBSR. The results demonstrated the cytoprotective effects of HYD-SBSR, as evidenced by reduced apoptosis rates and enhanced resistance to oxidative stress alongside moderate cell repair properties. Furthermore, this study investigated the impact of HYD-SBSR on antioxidant enzymes and peroxides in mice to elucidate its reparative potential in vivo. The findings revealed that HYD-SBSR exhibited remarkable antioxidant performance, particularly at low concentrations, significantly enhancing antioxidant capacity under oxidative stress conditions. To delve into the mechanisms underlying HYD-SBSR, a comprehensive proteomics analysis was conducted to identify differentially expressed proteins (DEPs). Additionally, a Gene Ontology (GO) analysis and an Encyclopedia of Genes and Genomes (KEGG) pathway cluster analysis were performed to elucidate the functional roles of these DEPs. The outcomes highlighted crucial mechanistic pathways associated with HYD-SBSR, including the PPAR signaling pathway, fat digestion and absorption, glycerophospholipid metabolism, and cholesterol metabolism. The research findings indicated that HYD-SBSR, as a health food supplement, exhibits favorable effects by promoting healthy lipid metabolism, contributing to the sustainable and environmentally friendly production of sea buckthorn and paving the way for future investigations and applications in the field of nutraceutical and pharmaceutical research.

Purpose. To explore the therapeutic efficiency of acupuncture and the related molecular mechanism of neural plasticity in depression. Methods. Chronic unpredictable mild stress- (CUMS-) induced rats were established for the depression animal model. There were a total of four rat groups, including the control group, the CUMS group, the CUMS+acupuncture group, and the CUMS+fluoxetine group. The acupuncture group and the fluoxetine group were given a 3-week treatment after the modeling intervention. The researcher performed the open-field, elevated plus maze, and sucrose preference tests to evaluate depressive behaviors. The number of nerve cells, dendrites’ length, and the prefrontal cortex’s spine density were detected using Golgi staining. The prefrontal cortex expression, such as BDNF, PSD95, SYN, and PKMZ protein, was detected using the western blot and RT-PCR. Results. Acupuncture could alleviate depressive-like behaviors and promote the recovery of the neural plasticity functions in the prefrontal cortex, showing the increasing cell numbers, prolonging the length of the dendrites, and enhancing the spine density. The neural plasticity-related proteins in the prefrontal cortex, including BDNF, PSD95, SYN, and PKMZ, were all downregulated in the CUMS-induced group; however, these effects could be partly reversed after being treated by acupuncture and fluoxetine (P

Excessive immune activation within the lesion site can be observed after stroke onset. Such neuroinflammation within the brain parenchyma represents the innate immune response, as well as the result of the additional interactions between peripheral and resident immune cells. Accumulative studies have illustrated that the pathological process of ischemic stroke is associated with resident and peripheral immunity. The infiltration of peripheral immune cells within the brain parenchyma implicitly contributes to secondary brain injuries. Therefore, better understanding of the roles of resident and peripheral immune reactions toward ischemic insult is necessary. In this review, we summarized the interaction between peripheral and resident immunity on systemic immunity and the clinical outcomes after stroke onset and also discussed various potential immunotherapeutic strategies.

Studying the spatial and temporal water distribution in the Lake Baikal Basin, which hosts the freshwater lake with the most water storage in the world, is essential to understand the water resources and environment of the basin and its impact and influence in terms of climate change and disaster prevention and mitigation. The basin spans two countries, Russia and Mongolia, which, along with its vastness, makes it challenging to accurately automate the acquisition of large-scale and long-term series data. The Google Earth Engine (GEE) is capable of processing large amounts of remote sensing imagery but does not support the computation and application of deep learning models. This study uses a combination of local deep learning training and GEE cloud-based big data intelligent computing to empower GEE with deep learning computing power, enabling it to rapidly automate the deployment of deep learning models. Visible light, near infrared (NIR), modified normalized difference water index (MNDWI), short-wave infrared 1 (SWIR1), linear enhancement band (LEB), and digital elevation model (DEM), which are more sensitive to water bodies, were selected as input features, along with the optimized input features of the existing pixel-based convolutional neural network (CNN) model. This method corrects the initial water labels from the Landsat quality assessment bands to reduce the time cost of manually drawing the labels and improving the classification accuracy of the water bodies. On average, only 1–2 h are required to generate the results for each water body product for each period in Lake Baikal Basin. The extraction of water bodies from the Lake Baikal Basin was achieved for nine yearly periods between 2013 and 2021. The validation accuracy was 92.9 %, 92.7 %, and 92.4 % for the three years 2013, 2017 and 2021, respectively. The results showed that the mean area of water bodies in the basin was 37,500 km2 and that the area of water bodies in the basin fluctuated without significant change from 2013 to 2021. This study provides methodological support for the continuous monitoring and assessment of water body dynamics at more catchment scales and other large scenarios.

A novel polysaccharide (ZOP) was extracted from Zingiber officinale with ultrasonic assisted extraction method. ZOP monosaccharide composition and mole ratio is GlcA: GalA: Glc: Gal: Ara = 1.97:1.15:94.33:1.48:1.07. Then, the particle size of ZOP-NPs prepared by nano-precipitation method was 230.5 nm, and the polydispersity index (PDI) was 0.260. Using ZOP and ZOP-NPs as reductants and stabilizers, ZOP-AgNPs and ZOP-NPs-AgNPs were prepared. They were characterized by ultraviolet-visible spectrophotometer (UV-Vis), fourier transform infrared spectroscopy (FT-IR), scanning electron microscope (SEM), transmission electron microscope (TEM), and X-ray diffraction (XRD). The silver chelation rate of polysaccharide silver nanoparticles (AgNPs) ranged from 68.70 to 82.12%. ZOP-AgNPs (0.5%, w/v; 1%, w/v) and ZOP-NPs-AgNPs (0.5%, w/v; 1%, w/v) exhibited a narrow particle size distribution of 31.1, 34.6, 25.1 and 27.6 nm, respectively. And the zeta potential values of them were−19.4,−21.6,−19.7,−23.8mV, respectively. The antioxidant and antibacterial activities of ZOP-NPs-AgNPs were superior to those of ZOP, ZOP-NPs and ZOP-AgNPs.

UV and external environmental stimuli can cause oxidative damage to skin cells. However, the molecular mechanisms involved in cell damage have not been systematically and clearly elucidated. In our study, an RNA-seq technique was used to determine the differentially expressed genes (DEGs) of the UVA/H2O2-induced model. Gene Oncology (GO) clustering and the Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway analysis were performed to determine the core DEGs and key signaling pathway. The PI3K-AKT signaling pathway was selected as playing a part in the oxidative process and was verified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). We selected three kinds of Schizophyllum commune fermented actives to evaluate whether the PI3K-AKT signaling pathway also plays a role in the resistance of active substances to oxidative damage. Results indicated that DEGs were mainly enriched in five categories: external stimulus response, oxidative stress, immunity, inflammation, and skin barrier regulation. S. commune-grain ferments can effectively reduce cellular oxidative damage through the PI3K-AKT pathway at both the cellular and molecular levels. Some typical mRNAs (COL1A1, COL1A2, COL4A5, FN1, IGF2, NR4A1, and PIK3R1) were detected, and the results obtained were consistent with those of RNA-seq. These results may give us a common set of standards or criteria for the screen of anti-oxidative actives in the future.

ABSTRACTBalamuthia mandrillaris infection is a rare and fatal disease. We have recorded 28 cases of Balamuthia mandrillaris infection during the past 20 years. Eighteen patients (64%) were male and 10 (36%) were female. Patient age ranged from 3 to 74 (mean, 27) years. Patient locations were distributed among 12 Provinces in China. Twenty-seven (96%) patients lived in rural areas, and 17 (61%) patients reported a history of trauma before the appearance of skin lesions. All cases presented with skin lesions as the primary symptom, and 16 (57%) cases developed encephalitis. Histopathology of skin lesions revealed granulomatous changes with histiocytes, lymphocytes, and plasma cells infiltration. Amebas were identified in all cases with immunohistochemical staining. Follow-up information was available in 27 (96%) cases. Fifteen (56%) patients died due to encephalitis and 12 (44%) were free of disease after treatment. Our results show that the clinical characteristics of Balamuthia mandrillaris infection in China are very different from those in the US. Infection of traumatized skin may play an important role in the pathogenesis of the disease in China. Encephalitis usually develops 3–4 years after skin lesions in Chinese cases. Patients with only skin lesions have a higher cure rate than patients with encephalitis.

The rainfall infiltration analysis method is an important method for slope stability forecast and prevention. Slope angle and unsaturated soil layers are not shown in the conventional Green-Ampt (GA) infiltration model. In this paper, based on the GA model of rainfall infiltration in tailings slopes, two aspects of slope angle and the proportion of the transition layer of the wet layer are modified. The rainfall infiltration test of unsaturated tailing soil was conducted using a self-developed large-size tailing slope model test device. The results of GA model, improved GA model, and Richards’ equation calculation model are compared. The results show that the difference between the three models is small in the free infiltration stage, but the infiltration rate is lower than that of the GA model. With the gradual increase of rainfall time into the ponding infiltration stage, the expansion depth and infiltration rate of the wetting front of the improved GA model and Richards’ equation are greater than those of the GA model. The difference between the GA model and the improved GA model and Richards’ equation for the extended depth of wetting front increases with the increase of rainfall duration, while the difference of infiltration rate changes in the opposite trend. The results of the improved GA model and Richards’ equation to calculate the expansion depth and infiltration rate of wetting fronts are consistent, and the difference basically tends to stabilize with the increase of rainfall ephemeris. The results of the improved GA model are closer to the measured data, which can provide a reference for analyzing the rainfall infiltration pattern of open pit tailing dams and slope stability research. On the basis of the improved GA model, the influence of slope angle, rain intensity, initial water content, and saturation infiltration coefficient on rainfall infiltration was analyzed, and the analysis of parameter sensitivity indexes showed that slope inclination and initial water content had a greater influence on the model.

We introduced a class of spiraling elliptic hollow beams with the cross phase. Due to the cross phase, the spiraling elliptic hollow beams exhibit three key characteristics, having the elliptic peak ring, carrying the orbital angular momentum (OAM), and performing rotations. We investigated both linear and nonlinear evolutions of the spiraling elliptic hollow beams, and found they can propagate stably, thanks to the cross phase. Especially, we obtained the breather states of spiraling elliptic hollow beams in nonlocally nonlinear medium, and could handily control the rotation by changing optical powers. We discussed both the OAM property and optical force property. By using the spiraling elliptic hollow beams, we can achieve a jointly multiple manipulation on particles at the same time. In one step, we can trap and simultaneously rotate the particles.

Most proteins given orally have low bioavailability and are easily eliminated by rapid metabolism in vivo. In order to immobilize the drug at the site of administration and delay its release, a natural, gentle release system was designed. In this study, a heteropolysaccharide (ZOP) was isolated from Zingiber officinale using an ultrasonic assisted extraction method. ZOP Ara = 1.97: 1.15: 94.33: 1.48: 1.07. The ZOP/Chitosan (CS) composite hydrogel was synthesized using epichlorohydrin (ECH) as a cross-linking agent. The structure, morphology, and water-holding capacity of the composite hydrogel were characterized. The data showed that the addition of ZOP improved the hardness and water-holding capacity of the material. A swelling ratio test showed that the prepared hydrogel was sensitive to pH and ionic strength. In addition, the degradation rate of the hydrogel in a phosphate-buffered saline (PBS) solution with a pH value of 1.2 was higher than that in PBS with pH value of 7.4. Similarly, the release kinetics of Bovine serum albumin (BSA) showed higher release in an acidic system by the hydrogel composed of ZOP/CS. The hydrogel prepared by this study provided a good microenvironment for protein delivery. In summary, this composite polysaccharide hydrogel is a promising protein-drug-delivery material.

Ectoin is an amino acid derivative that can create a balance between the osmotic pressure of cells and can protect enzymes, DNA proteins, and nucleic acids under extreme conditions. Ectoin has also been reported to slow skin aging. However, there are few reports on the protective effect of Ectoin on oxidative damage, especially on the regulation of PI3K/AKT-pathway-related genes at the mRNA level. UVA-induced oxidative stress injury and H2O2-induced oxidative stress injury are two common oxidative stress injury models. Skin fibroblasts produce a large number of ROS following excessive UV radiation or oxidative stimulation by H2O2, which further inhibits cell proliferation and causes cell apoptosis. In this study, UVA- and H2O2-induced oxidation models of human skin fibroblasts were established separately to investigate the protective effect of Ectoin. Further studies on the mechanisms involved, for example, the expression levels of genes associated with the PI3K/AKT signaling pathway and levels of antioxidant enzymes in cells, were determined. We found that Ectoin upregulated genes associated with the PI3K/AKT signaling pathway, including COL1A1, COL1A2, FN1, IGF2, NR4A1, and PIK3R1, but decreased intracellular ROS levels and malondialdehyde (MDA), while increasing the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). In conclusion, our results indicate that Ectoin exerts protective properties by the upregulated genes COL1A1, COL1A2, FN1, IGF2, NR4A1, and PIK3R1 and upregulating antioxidative enzyme levels.

Analytically discussed is the evolution properties of optical vortices superimposed by Gaussian backgrounds. A kind of Tornado-like pattern is obtained after linear propagations, when the Gaussian background is wide enough compared with optical vortices. The same structures are exhibited by the intensity and the phase for the Tornado-like pattern, and the latter can be regarded as a clockwise rotation of the former. The gradient force exerted by the Tornado-like pattern upon micro-particles is investigated from the application point of view in optical tweezers. Compared to conventional optical vortices, the Tornado-like pattern shows the superior performance on the trapping ability for microparticles.

Abstract In this report, we present a pH-induced reversible assembly system (PIRAS) based on ferritin (Ft) for targeted tumor therapy. It has been developed to easily load and release of the anticancer drug resveratrol (RV), based on its natural pH-sensitivity and unique hollow cavity of Ft. A tumor-specific target peptide Arg-Gly-Asp (RGD) was conjugated onto the surface of RV-loaded Ft (RV@Ft), to form biocompatible nanoparticles (RV@Ft-RGD). The pH-sensitivity of Ft allows it to be denatured into a hollow porous nanosphere under acidic condition and renatured into a sealed hollow nanosphere under neutral condition. Using pH manipulation, RV@Ft-RGD, with a ~ 21 nm diameter, showed a high RV loading ratio of 79.6%. pH-triggered RV release was then measured at a ratio of 50.3% at pH5.0 over 24 h. Under neutral condition, the RV@Ft-RGD showed excellent stability over 20 days. Confocal fluorescence imaging showed that RV@Ft-RGD had a high cell uptake ratio and co-localization with the lysosome, mainly due to the RGD-mediated target effect. Based on the high drug loading, pH-triggered release, and tumor cell targeting effect, RV@Ft-RGD showed great cell-killing ability in vitro and in vivo. The biocompatibility in vitro and in vivo was also demonstrated to be excellent, without systematic toxicity. The design concept of PIRAS based on Ft significantly inhibits tumor growth and simultaneously further broadens the application of Ft in nanomedicine.

Abstract Background Lycopene is an important carotenoid pigment in red fruits and vegetables, especially in tomato. Although lycopene biosynthesis and catabolism have been found to be regulated by multiple factors including phytohormones, little is known about their regulatory mechanism. Cytokinins are crucial to various aspects of plant growth. Isopentenyltransferases (IPTs) catalyze the initial rate-limiting step of cytokinins biosynthesis, however, their roles in fruit ripening remain unclear. Results Here, the functions of SlIPT4, encoding an isopentenyltransferase, were characterized via RNAi-mediated gene silencing in tomato. As we expected, silencing of SlIPT4 expression resulted in accelerated leaf senescence. However, down-expression of SlIPT4 generated never-red orange fruits, corresponding with a dramatic reduction of lycopene. Among lycopene biosynthesis-related genes, the fact of remarkable decrease of ZISO transcript and upregulation of other genes, revealed that SlIPT4 regulates positively lycopene biosynthesis via directly affecting ZISO expression, and also supported the existence of regulatory loops in lycopene biosynthesis pathway. Meanwhile, the accumulation of abscisic acid (ABA) was reduced and the transcripts PSY1 were increased in SlIPT4-RNAi fruits, supporting the feedback regulation between ABA and lycopene biosynthesis. Conclusion The study revealed the crucial roles of SlIPT4 in leaf senescence and the regulatory network of lycopene biosynthesis in tomato, providing a new light on the lycopene biosynthesis and fruit ripening.

Objective. To expand upon the role of iguratimod (T-614) in the treatment of rheumatoid arthritis (RA), we investigated whether the Th1, Th17, follicular helper T cells (Tfh), and regulatory T cells (Treg) imbalance could be reversed by iguratimod and the clinical implications of this reversal. Methods. In this trial, 74 patients were randomized into iguratimod-treated (group A) and control (broup B) group for a 24-week treatment period. In the subsequent 28 weeks, both groups were given iguratimod. Frequencies of Th1, Th17, Tfh, and Treg were quantified using flow cytometry, and serum cytokines were detected by enzyme-linked immunosorbent assay. mRNA expression of cytokines and transcriptional factor were quantified by RT-PCR. The composite Disease Activity Score, erythrocyte sedimentation rate, and C-reactive protein were assessed at each visit. Result. The clinical scores demonstrated effective suppression of disease after treatment with iguratimod. In addition, iguratimod downregulated Th1, Th17-type response and upregulated Treg. Furthermore, the levels of Th1, Th17, and Tfh associated inflammatory cytokines and transcription factors were reduced after treatment with iguratimod, while the levels of Treg associated cytokines and transcription factors were increased.

Multiple sclerosis is an autoimmune disease with classical traits of demyelination, axonal damage, and neurodegeneration. The migration of autoimmune T cells and macrophages from blood to central nervous system as well as the destruction of blood brain barrier are thought to be the major processes in the development of this disease. Chemokines, which are small peptide mediators, can attract pathogenic cells to the sites of inflammation. Each helper T cell subset expresses different chemokine receptors so as to exert their different functions in the pathogenesis of MS. Recently published results have shown that the levels of some chemokines and chemokine receptors are increased in blood and cerebrospinal fluid of MS patients. This review describes the advanced researches on the role of chemokines and chemokine receptors in the development of MS and discusses the potential therapy of this disease targeting the chemokine network.

To observe the effect of curcumin treatment on serum inflammatory factors in rats with traumatic arthritis and explores the protective effect of articular surface cartilage in rats with traumatic arthritis. A control group (group A), a model group (group B), and a curcumin group (group C) were randomly chosen. Except for the group A, the curcumin model was established by removing the medial meniscus of the right knee in the other two groups. After the model was successfully established, the group C was intraperitoneally injected with curcumin solution 50 mg/kg, while the group A and B were injected with the same volume of dimethyl sulfoxide solution for 28 d. The levels of serum vascular endothelial growth factor and tumor necrosis factoralpha and interleukin-1 beta were measured by enzyme-linked immunosorbent assay method. The arthritis index score of the two groups was calculated, the pathological morphology of articular cartilage was observed by hematoxylin and eosin staining, and the apoptosis rate of knee chondrocytes was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Real-time polymerase chain reaction and Western blot methods were used to detect the expression of autophagy and apoptosis regulatory molecules Beclin-1, B-cell lymphoma 2, caspase-3, messenger ribonucleic acid and protein in knee cartilage. Curcumin can protect the articular surface cartilage of traumatic arthritis rats by reducing inflammatory factors in serum and regulating the apoptosis and autophagy of articular chondrocytes. Curcumin may be a potential drug for the treatment of traumatic arthritis. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) belongs to the class of significantly malignant tumors found in humans. Recently, dysregulated fatty acid metabolism (FAM) has been a topic of attention due to its modulation in cancer, specifically CRC. However, the regulatory FAM pathways in CRC require comprehensive elucidation. Methods: The clinical and gene expression data of 175 fatty acid metabolic genes (FAMGs) linked with colon adenocarcinoma (COAD) and normal cornerstone genes were gathered through The Cancer Genome Atlas (TCGA)-COAD corroborating with the Molecular Signature Database v7.2 (MSigDB). Initially, crucial prognostic genes were selected by uni- and multi-variate Cox proportional regression analyses; then, depending upon these identified signature genes and clinical variables, a nomogram was generated. Lastly, to assess tumor immune characteristics, concomitant evaluation of tumor immune evasion/risk scoring were elucidated. Results: A 8-gene signature, including ACBD4, ACOX1, CD36, CPT2, ELOVL3, ELOVL6, ENO3, and SUCLG2, was generated, and depending upon this, CRC patients were categorized within high-risk (H-R) and low-risk (L-R) cohorts. Furthermore, risk and age-based nomograms indicated moderate discrimination and good calibration. The data confirmed that the 8-gene model efficiently predicted CRC patients' prognosis. Moreover, according to the conjoint analysis of tumor immune evasion and the risk scorings, the H-R cohort had an immunosuppressive tumor microenvironment, which caused a substandard prognosis. Conclusion: This investigation established a FAMGs-based prognostic model with substantially high predictive value, providing the possibility for improved individualized treatment for CRC individuals. [ABSTRACT FROM AUTHOR]

Schizophyllum commune is a fungus with applications both in medicine and foods, which produces IPS and EPS. However, there is no comparative study on the activity comparison of IPS and EPS and its mechanism of antioxidant effect. In this study, the antioxidant activities of the two polysaccharides were measured in biochemical, cellular and molecular levels, and H2O2 induced oxidative damage model of HSFs was established to explore the protective effects of EPS and IPS. We found IPS and EPS both achieved a good antioxidant effect. They can also improve the cellular levels of SOD and reduce MDA. Insights regarding the molecular mechanism were studied, we found that both EPS and IPS could increase the expression of Nrf2 in Keap1-Nrf2/ARE signaling pathway. At the same time, they could inhibit the expression of the negative feedback gene Keap1 and promote the expression of downstream gene GCLC, Gstt-1, Nqo1 and Ho-1. [ABSTRACT FROM AUTHOR]

Skin microbiome is closely related to skin health. It plays an important role in maintaining skin health, resisting the invasion of foreign microorganisms and participating in skin tissue metabolism. It also provides ideas for the research and development of skin therapeutic drugs and skin care products. In recent years, the literatures on skin microecology are increasing year by year. With the help of literature measurement method and knowledge map visualization software VOSviewer, this paper made quantitative statistics and comparative analysis on the distribution trend, distribution volume of major countries, distribution institutions and research topics from 2010 to 2022. The results show that in recent years, the research in the field of skin microecology has attracted worldwide attention. Its research topics mainly include "skin diseases caused by microecological imbalance and the relationship, pathogenesis and mechanism between some skin diseases and skin microorganisms", "skin problems caused by harmful flora", "diversity of skin microorganisms and influencing factors of colonization", and "genetic correlation of skin microbial community". The majority researches focus on the imbalance of skin microecology and the diversity of skin microorganisms. Then, the differences in research fields between China and the United States are analyzed and compared. The United States researchers mainly focus on the technical means of skin microorganisms, and the Chinese mainly focus on the research of three skin diseases. [ABSTRACT FROM AUTHOR]

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In this paper, we report fine tunable red-green upconversion luminescence of glass ceramic containing 5%Er3+: NaYF4 nanocrystals excited simultaneously by two near infrared femtosecond lasers. When the glass ceramic was irradiated by 800nm femtosecond laser, weak red emission centered at 670 nm was detected. Bright red light was observed when the fs laser wavelength was tuned to 1490 nm. However, when excited by the two fs lasers simultaneously, the sample emitted bright green light centered at 550 nm, while the red light kept the same intensity. The dependences of the red and the green light intensities on the two pump lasers are much different, which enables us to manipulate the color emission by adjusting the two pump laser intensities, respectively. We present a theoretical model of Er3+ ions interacting with two fs laser fields, and explain well the experimental results. [ABSTRACT FROM AUTHOR]

Background: Neuroinflammation plays hypertensive roles in the uninjured autonomic nuclei of the central nervous system, while its mechanisms remain unclear. The present study is to investigate the effect of neuroinflammation on autophagy in the neurons of the rostral ventrolateral medulla (RVLM), where sympathetic premotor neurons for the maintenance of vasomotor tone reside.Methods: Stress-induced hypertension (SIH) was induced by electric foot-shock stressors with noise interventions in rats. Systolic blood pressure (SBP) and the power density of the low frequency (LF) component of the SAP spectrum were measured to reflect sympathetic vasomotor activity. Microglia activation and pro-inflammatory cytokines (PICs (IL-1β, TNF-α)) expression in the RVLM were measured by immunoblotting and immunostaining. Autophagy and autophagic vacuoles (AVs) were examined by autophagic marker (LC3 and p62) expression and transmission electron microscopy (TEM) image, respectively. Autophagy flux was evaluated by RFP-GFP-tandem fluorescent LC3 (tf-LC3) vectors transfected into the RVLM. Tissue levels of glutamate, gamma aminobutyric acid (GABA), and plasma levels of norepinephrine (NE) were measured by using high-performance liquid chromatography (HPLC) with electrochemical detection. The effects of the cisterna magna infused minocycline, a microglia activation inhibitor, on the abovementioned parameters were analyzed.Results: SIH rats showed increased SBP, plasma NE accompanied by an increase in LF component of the SBP spectrum. Microglia activation and PICs expression was increased in SIH rats. TEM demonstrated that stress led to the accumulation of AVs in the RVLM of SIH rats. In addition to the Tf-LC3 assay, the concurrent increased level of LC3-II and p62 suggested the impairment of autophagic flux in SIH rats. To the contrary, minocycline facilitated autophagic flux and induced a hypotensive effect with attenuated microglia activation and decreased PICs in the RVLM of SIH rats. Furthermore, SIH rats showed higher levels of glutamate and lower level of GABA in the RVLM, while minocycline attenuated the decrease in GABA and the increase in glutamate of SIH rats.Conclusions: Collectively, we concluded that the neuroinflammation might impair autophagic flux and induced neural excitotoxicity in the RVLM neurons following SIH, which is involved in the development of SIH. [ABSTRACT FROM AUTHOR]

Microglial activation has been recognized as being vital in the pathogenesis of several neurodegenerative disorders. Therefore, the identification of therapeutic drugs to prevent microglial activation and thus protect against inflammation-mediated neuronal injury, is required. In the present study, dextromethorphan (DM), a compound widely used in antitussive remedies that has been demonstrated to possess neuroprotective effects, was shown to reduce proinflammatory mediator production in lipopolysaccharide (LPS)-stimulated BV2 mouse microglial cells. Western blot analysis revealed that DM markedly suppressed the activation of nuclear factor-κB (NFκB), caspase-3 signaling and the expression of another inflammation-inducing factor, heat shock protein 60 (HSP60) and heat shock factor-1, induced by LPS in BV2 cells. Results from ELISA assay demonstrated that DM reduced the release of HSP60, nitric oxide (NO), inducible NO synthase, tumor necrosis factor-α, interleukin (IL)-1β and IL-6 induced by LPS in BV2 microglia. These results were confirmed by immunofluorescence, suggesting that DM may exert a neuroprotective and anti-inflammatory effect by inhibiting microglial activation through the HSP60-NFκB signaling pathway. Therefore, DM may offer substantial therapeutic benefits in the treatment of neurodegenerative diseases that are accompanied by microglial activation. [ABSTRACT FROM AUTHOR]

Heat shock protein (HSP)60 is primarily a mitochondrial protein. Previous experiments have found that changes in the location of intracellular HSP60 have been associated with apoptosis. Extracellular HSP60 mediates apoptosis via its ligand, Toll-like receptor (TLR)-4. TLR-4 is an important factor expressed on microglia, with a central role in generating neuroimmune responses in the pathogenesis of neurodegenerative disorders. Naloxone is a highly effective nonselective opioid receptor antagonist, and has been reported to be pharmacologically beneficial for the treatment of brain diseases through inhibiting microglia activation. However, the mechanisms underlying these beneficial effects of naloxone remain poorly understood. The present study aimed to investigate the role of HSP60 in the neuroprotective effects of naloxone on the production of proinflammatory mediators in lipopolysaccharide (LPS)-stimulated BV2 murine microglial cells and the possible signaling pathways involved. The results demonstrated that naloxone significantly inhibited the expression and release of HSP60 in BV2 cells. The expression levels of heat shock factor (HSF)-1 were upregulated in LPS-activated BV2 cells, which indicated that the increased expression of HSP60 was driven by HSF-1 activation. However, increased HSF-1 levels may be downregulated by naloxone. The levels of TLR-4 were elevated in activated BV2 cells, and then inhibited by naloxone. Activation of TLR-4 is characterized by activation of nuclear factor-κB (NF-κB) followed by the production of various proinflammatory and neurotoxic factors. Data from the present study demonstrated that naloxone reduced the expression levels of NF-κB and its upstream protein caspase-3, and reduced the LPS-induced production of nitric oxide, inducible nitric oxide synthase, tumor necrosis factor α, interleukin-1β and interleukin-6 in BV2 microglia. In light of this data, it was concluded that naloxone may exert its neuroprotective and anti-inflammatory effects by inhibiting microglia activation through a HSP60-TLR-4-NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]

We introduce the anisotropy into the evolutions of the vortex, and discuss three different kinds of dynamics: circular shaped vortex in linear anisotropic media, elliptic shaped vortex in linear isotropic media, and elliptic shaped vortex in linear anisotropic media. The evolutionary processes dramatically depend on both the anisotropic parameter δM of the media and the initial aspect ratio ρ0 of the elliptic vortex. Under the critical condition , the elliptic vortex will not rotate, and keeps its aspect ratio invariant during the evolutions. Generally, when , the dynamics of the elliptic vortex can be divided into three stages: nonuniform process, rotational process and uniform process. In the nonuniform and the uniform processes of the vortex, the positions of the outer elliptic peaks and the inner elliptic holes do not change in spite of the nonzero energy flow. Also, the energy distributions become nonuniform in the former process, and uniform in the latter process. In the rotational process, the outer peaks and the inner holes can both rotate, but with the opposite rotational directions. [ABSTRACT FROM AUTHOR]

It has been shown that the femtosecond laser polarization modulation is a very simple and well-established method to control the multi-photon absorption process by the light–matter interaction. Previous studies mainly focused on the multi-photon absorption control in the weak field. In this paper, we further explore the polarization control behavior of multi-photon absorption process in the intermediate femtosecond laser field. In the weak femtosecond laser field, the second-order perturbation theory can well describe the non-resonant two-photon absorption process. However, the higher order nonlinear effect (e.g., four-photon absorption) can occur in the intermediate femtosecond laser field, and thus it is necessary to establish new theoretical model to describe the multi-photon absorption process, which includes the two-photon and four-photon transitions. Here, we construct a fourth-order perturbation theory to study the polarization control behavior of this multi-photon absorption under the intermediate femtosecond laser field excitation, and our theoretical results show that the two-photon and four-photon excitation pathways can induce a coherent interference, while the coherent interference is constructive or destructive that depends on the femtosecond laser center frequency. Moreover, the two-photon and four-photon transitions have the different polarization control efficiency, and the four-photon absorption can obtain the higher polarization control efficiency. Thus, the polarization control efficiency of the whole excitation process can be increased or decreased by properly designing the femtosecond laser field intensity and laser center frequency. These studies can provide a clear physical picture for understanding and controlling the multi-photon absorption process in the intermediate femtosecond laser field, and also can provide a theoretical guidance for the future experimental realization. [ABSTRACT FROM AUTHOR]