Search

Compound 1 was previously identified by our team as a glycogen phosphorylase (GP) inhibitor with glucose-lowering activity and demonstrated to have protective effects against myocardial and cerebral ischemia. However, its impact on muscle function has not been clarified. This study is the first to evaluate the long-term effects of GP inhibitors on muscle function and metabolism. After a 28-day administration of Compound 1, we performed assays to assess muscle function and biochemical parameters in rats. We observed reductions in peak holding force, duration, tetanic contraction force, single-contraction force, and electromyographic signals under 20 s and 10 min contraction stimuli. The metabolic analysis showed no significant effects on muscle glycogen, ATP, lactic acid, and uric acid levels at low doses. In contrast, medium to high doses resulted in increased glycogen, decreased ATP, and reduced lactic acid (only at high doses), without affecting uric acid. These findings suggest that Compound 1 may adversely affect muscle function in rats, potentially due to the glycogen inhibition effects of GP inhibitors. This study provides crucial safety data and insights into the long-term effects of GP inhibitors on rat muscles, which will guide future developments and applications.

Pectin was extracted from Actinidia arguta Sieb. et Zucc (A.arguta) using the ultrasound-assisted acid method and the single acid method. The physicochemical properties, structure, and antioxidant properties of two different pectins were investigated. The results showed that the extraction yield of the ultrasound-assisted acid method is higher than that of the single acid method. The molecular structure of A. arguta pectin extracted by the ultrasound-assisted acid method belongs to a mixed structure of RG-I and HG-type domains. Through structural feature analysis, the ultrasound-assisted extraction pectin (UAP) has a more branched structure than the single acid-extracted pectin (SAP). The SAP has a higher degree of esterification than the UAP. The physical property results show that the viscosity, solubility, and water-holding capacity of the UAP are better than those of the SAP. The antioxidant test results show that the hydroxyl radical scavenging and reducing powers of the UAP are superior to those of the SAP. This study shows the composition, physicochemical properties, and antioxidant activity of A. arguta pectin extracted by the ultrasonic-assisted extraction method to provide a theoretical basis for its application as an antioxidant and other food additives in the food industry.

Aging is a major risk factor for the development of many pathological processes, such as reduced immunity, cancer, cardiovascular diseases or neurodegenerative diseases, while age-related chronic diseases are the most common causes of death. This paper studies the effects of American ginseng saponin Rb1 and Re alone and combined intervention on the immune system of aging mouse models, by using 30 mg/kg Rb1, 15 mg/kg Re, and Rb1 + Re (30 mg/kg Rb1 and 15 mg/kg Re (co-intervention) was used to intervene in the aging model, and immune indicators such as thymus index, spleen index, interleukin and interferon were detected to evaluate the impact of Rb1 and Re on immune function. The results show that Rb1 and Re intervention alone can increase the spleen index by 7%–12% and the thymus index by 12%–19% in the aging model. After Rb1 or Re alone intervened, the apoptotic cells in the thymus were slightly reduced, and the proportion of apoptotic cells was reduced. The combination of Rb1 + Re can promote the thymus index and spleen index to increase by 23.40% and 25.5% respectively, which is more advantageous than Rb1 or Re alone. In addition, Rb1 and Re intervention can reduce the level of interferon INF to a level comparable to that of young mice. Rb1 + Re can not only reduce the INF content, but also reduce the TNF content. The above results show that American ginseng saponin Rb1 and Re can delay the decline of the immune system in the aging model, and the combined intervention of the two is significantly better than individual intervention in the recovery of the immune system. This paper can provide theoretical basis and data support for the development of American ginseng nutritional supplements and its application in aging groups products to improve immunity.

Transflective electrochromic (EC) materials with the ability to dynamically adjust color in both reflection and transmission mode are extremely attractive for tunable filter, smart windows, and ultralow-power displays due to their wide applicability in dark and bright environment and unique tunability of optical properties. However, simultaneously brilliant multicolor modulation of both reflection and transmission in one EC film is challenging. Here, integrated and metal/dielectric structured EC electrode composed of three-layered Cr/Ag/WO3 (CAW) films are demonstrated. Benefiting from the synergistic effect of the good conductivity, strong optical interference, and excellent substrate-film adhesion, these well-designed CAW films successfully demonstrate dynamic variegated modulation of both reflective and transmissive colors. This modulation encompasses a broad spectrum of hues, boasts high saturation, rapid response times, and exhibits impressive cycling stability. The flexible CAW film with superior bending stability is also achieved for the successful construction of the patterned flexible EC device.

Plant diseases caused by pathogenic fungi seriously affect the yield and quality of crops, cause huge economic losses, and pose a considerable threat to global food security. Phenylpyrrole analogues were designed and synthesized based on alkaloid lycogalic acid. All target compounds were characterized by 1H NMR, 13C NMR, and HRMS. Their antifungal activities against seven kinds of phytopathogenic fungi were evaluated. The results revealed that most compounds had broad-spectrum fungicidal activities at 50 μg/mL; 14 compounds displayed more than 60% fungicidal activities against Rhizoctonia cerealis and Sclerotinia sclerotiorum, and in particular, the fungicidal activities of compounds 8g and 8h against Rhizoctonia cerealis were more than 90%, which could be further developed as lead agents for water-soluble fungicides. The molecular docking results indicate that compounds 8g and 8h can interact with 14α-demethylase (RcCYP51) through hydrogen bonding with strong affinity.

Acute lung injury (ALI) is one of the most serious complications of sepsis, characterized by high morbidity and mortality rates. Ferroptosis has recently been reported to play an essential role in sepsis-induced ALI. Excessive neutrophil extracellular traps (NETs) formation induces exacerbated inflammation and is crucial to the development of ALI. In this study, we explored the effects of ferroptosis and NETs and observed the therapeutic function of mesenchymal stem cells (MSCs) on sepsis-induced ALI. First, we produced a cecal ligation and puncture (CLP) model of sepsis in rats. Ferrostain-1 and DNase-1 were used to inhibit ferroptosis and NETs formation separately, to confirm their effects on sepsis-induced ALI. Next, U0126 was applied to suppress the MEK/ERK signaling pathway, which is considered to be vital to NETs formation. Finally, the therapeutic effect of MSCs was observed on CLP models. The results demonstrated that both ferrostain-1 and DNase-1 application could improve sepsis-induced ALI. DNase-1 inhibited ferroptosis significantly in lung tissues, showing that ferroptosis could be regulated by NETs formation. With the inhibition of the MEK/ERK signaling pathway by U0126, NETs formation and ferroptosis in lung tissues were both reduced, and sepsis-induced ALI was improved. MSCs also had a similar protective effect against sepsis-induced ALI, not only inhibiting MEK/ERK signaling pathway-mediated NETs formation, but also alleviating ferroptosis in lung tissues. We concluded that MSCs could protect against sepsis-induced ALI by suppressing NETs formation and ferroptosis in lung tissues. In this study, we found that NETs formation and ferroptosis were both potential therapeutic targets for the treatment of sepsis-induced ALI, and provided new evidence supporting the clinical application of MSCs in sepsis-induced ALI treatment.

Combined bodies of rock-like material and rock are widely encountered in geotechnical engineering, such as tunnels and mines. The existing theoretical models describing the stress-strain relationship of a combined body lack a binary feature. Based on effective medium theory, this paper presents the governing equation of the “elastic modulus” for combined and single bodies under triaxial compressive tests. A binary effective medium model is then established. Based on the compressive experiment of concrete-granite combined bodies, the feasibility of determining the stress threshold based on crack axial strain is discussed, and the model is verified. The model is further extended to coal-rock combined bodies of more diverse types, and the variation laws of the compressive mechanical parameters are then discussed. The results show that the fitting accuracy of the model with the experimental curves of the concrete-granite combined bodies and various types of coal-rock combined bodies are over 95%. The crack axial strain method can replace the crack volumetric strain method, which clarifies the physical meanings of the model parameters. The variation laws of matrix parameters and crack parameters are discussed in depth and are expected to be more widely used in geotechnical engineering.

Bedrock and concrete lining are typical composite structures in the engineering field and the stability of the geological body and engineering body is directly connected to the mechanical properties of the composite body. Under this background, the study provides the transverse isotropic equivalent model of concrete-granite double-layer composite based on the notion of strain energy equivalence. Assuming that the strength failure of concrete and granite meets the Mohr-Coulomb criterion, then the strength failure model of the combined body considering the joint roughness coefficient (JRC) is derived, and the influences of JRC, the height ratio of concrete to granite, and confining pressure on the strength failure characteristics of the combined body are emphatically analyzed. Finally, the model applicability is illustrated by the uniaxial and triaxial compression tests on concrete monomer, granite monomer and concrete-granite composite samples (CGCSs) with different JRCs. The results revealed that the compressive strength of the composite is closer to the concrete with lower strength in the combined body under different confining pressures. Adding interface roughness causes to raise the compressive strength of the composite due to interfacial adhesion between concrete and granite, and a slowing growth trend is observed in compressive strength as roughness. The model can provide a certain reference for the stability design and evaluation of engineering rock mass.

Video propaganda is reported effectively improving patients' understanding of operation. However, whether a video introducing patients' most concerns can reduce preoperative anxiety and promote recovery stays unsealed. In this study, we investigated the effects of complementary therapy of educational video during preoperative visit. The results showed that thirty-five (23.2%) parents in Group Control were diagnosed as anxiety according to SAS, and nineteen (12.3%) patients were diagnosed after video intervention. The APAIs anxiety score and APAIs information score in Group Video were lower than those in Group Control. Compared with Group Control, video visit helped to increase the first-attempt pass rate of the knowledge retention exam and solve the patient's most worried concerns, and decrease incidence of emergence agitation, total cost of hospitalization and length of hospital stay. Moreover, video visit improved satisfaction degrees of patients and their main family members. Briefly, our study demonstrated video visit can improve patients' knowledge of anesthesia and decrease their preoperative anxiety, which may represent an important complementary therapy to routine preoperative visits.

Objective To compare the clinical efficacy of percutaneous minimally invasive reduction combined with external fixation and a tarsal sinus approach to treat Sanders type II and III intra‐articular calcaneal fractures. Methods The clinical data of 64 patients with Sanders type II and III calcaneal fractures admitted to our hospital from January 2010 to January 2016 were retrospectively analyzed; data includedage, sex, body mass index. According to the surgical method, they were divided into the percutaneous minimally invasive reduction with internal and external fixation group (30 cases) and the tarsal sinus approach group (34 cases).The two groups of patients were compared in terms of the time tosurgery, length of hospital stay, intraoperative blood loss, operative duration, complications, radiographic features, including the heel bone length, width, height, Bohlerangle, Gissane angle, and calcaneal varus angle, and clinical efficacy indicators, including the American Orthopedic Foot and Ankle Society (AOFAS) score, the visual analog scale (VAS) pain score, health survey profile (SF‐36) score and Maryland ankle function score. Results Patients in both groups were followed up for 12 to 50 months, with an average of 24.8 months.Bony union was achieved in all cases. The time to surgery, length of hospitalstay, intraoperative blood loss and incidence of incision‐related complications were significantly lower in the percutaneous minimally invasive medial external fixation group than in the tarsal sinus group (P 0.05). As measures of clinical efficacy, the AOFAS, VAS, SF‐36 and Maryland scores were 85.28 ± 8.21, 0.84 ± 1.21, 82.95 ± 3.25 and 83.56 ± 3.32, respectively, at the last follow‐up in the percutaneous minimally invasive medial external fixation group and 83.32 ± 7.69, 1.85 ± 1.32, 80.71 ± 5.42, and 81.85 ± 2.41 in the tarsal sinus group, respectively, with no significant differences between the two groups (P > 0.05). Conclusion Under the condition of a good command of surgical indications and surgical skills, the use of plastic calcaneal forceps for percutaneous minimally invasive reduction combined with medial external fixation for the treatment of Sanders type II and III intra‐articular calcaneal fractures can achieve similar clinical effects as the tarsal sinus approach. However, the use of plastic calcaneal forceps for percutaneous minimally invasive reduction combined with internal and external fixation has advantages, such as fewer complications, less bloodloss, and a shorter operation, and thus has good safety and is worthy of clinical promotion.

Abstract Metal–organic frameworks (MOFs) are recognized as promising electrocatalysts for the oxygen evolution reaction (OER) because of their permanent porosity and rich architectural diversity; however, ionic MOFs enabling fast ions exchange during OER are rarely explored. Here, an ionic MOF (Ni‐btz) constructed with an azolate ligand is selected, and continuous 3D bimetallic MOF (NiFe‐btz) films deriving from high‐degree intergrowth of microsized MOFs particles are fabricated. The as‐prepared NiFe‐btz/NF‐OH electrode exhibits excellent OER performance with a low overpotential of 239 mV at 10 mA cm−2 under alkaline condition. The OER charge transfer process and bimetallic coupling effect in ionic NiFe‐btz are probed by density functional theory calculations and confirmed via X‐ray photoelectron spectroscopy and in situ Raman measurements. The partial density of states of NiFe‐btz indicates that the main contribution for electron density around the Fermi level is from Cl ions clarifying the profitable impact of ionic MOF framework. This work systematically demonstrates the relationship of electronic structure and OER activity in ionic, bimetallic MOFs and expands the scope of 3D MOF films for efficient OER.

ELMO1 (Engulfment and Cell Motility1) is a gene involved in regulating cell motility through the ELMO1-DOCK2-RAC complex. Contrary to DOCK2 (Dedicator of Cytokinesis 2) deficiency, which has been reported to be associated with immunodeficiency diseases, variants of ELMO1 have been associated with autoimmune diseases, such as diabetes and rheumatoid arthritis (RA). To explore the function of ELMO1 in immune cells and to verify the functions of novel ELMO1 variants in vivo, we established a zebrafish elmo1 mutant model. Live imaging revealed that, similar to mammals, the motility of neutrophils and T-cells was largely attenuated in zebrafish mutants. Consequently, the response of neutrophils to injury or bacterial infection was significantly reduced in the mutants. Furthermore, the reduced mobility of neutrophils could be rescued by the expression of constitutively activated Rac proteins, suggesting that zebrafish elmo1 mutant functions via a conserved mechanism. With this mutant, three novel human ELMO1 variants were transiently and specifically expressed in zebrafish neutrophils. Two variants, p.E90K (c.268G>A) and p.D194G (c.581A>G), could efficiently recover the motility defect of neutrophils in the elmo1 mutant; however, the p.R354X (c.1060C>T) variant failed to rescue the mutant. Based on those results, we identified that zebrafish elmo1 plays conserved roles in cell motility, similar to higher vertebrates. Using the transient-expression assay, zebrafish elmo1 mutants could serve as an effective model for human variant verification in vivo.

Transparent displays are one of the development directions of future displays, and have great application potential in smart windows, wearable electronic products, virtual reality technology, touch screens and other fields. Perovskite materials have high fluorescence quantum efficiency and high color purity, which make a thin luminous layer achieve high device performance, making us foresee their potential application in the field of transparent displays in the future. However, due to the limitations of the modulation of the luminescent layer and top transparent electrodes, the performance of transparent perovskite light-emitting diodes (TPeLEDs) still has a certain gap compared to the traditional perovskite light-emitting diodes (PeLEDs). In this work, the first blue emitted TPeLEDs were prepared by using quasi two-dimensional perovskite materials and multilayer transparent top electrodes. By designing and optimizing the performance of the luminescent layer and the structure of the top transparent electrode, the transmittance and device efficiency of TPeLEDs were enhanced. The best TPeLED shows a maximum transmittance of nearly 70%, and displays a maximum brightness of 2294 cd m2 and a maximum external quantum efficiency (EQE) of 11.73%. [ABSTRACT FROM AUTHOR]

Background and Purpose: Acute lung injury (ALI) is a serious, life-threatening inflammation of the lungs that still lacks effective treatment. We previously showed that serine protease inhibitor B1 (SerpinB1) protects against ALI induced by orthotopic autologous liver transplantation. However, the role of SerpinB1 in lipopolysaccharide (LPS)-induced ALI and its regulatory mechanisms are not known. Experimental Approach: Wild-type (WT) and SerpinB1 knockout (KO) mice were treated with intratracheal LPS stimulation to induce ALI. Some of the WT and KO mice were injected i.p. with melatonin, a rhythm-related protein Rev-erbα agonist. The circadian rhythm in WT mice was disrupted by exposing mice to 24 h of continuous dark or light conditions after intratracheal LPS. Neutrophils were isolated from alveolar lavage fluid of WT and KO mice, and from human peripheral blood. Neutrophils were treated with LPS and melatonin. Key Results: Disruption of circadian rhythm by either 24-h dark or light conditions exacerbated LPS-induced ALI and decreased expression of Rev-erbα and SerpinB1 protein in lung, whereas melatonin treatment increased SerpinB1 expression and attenuated LPS-induced ALI in WT mice, but not in KO mice. In isolated neutrophils, Rev-erbα was co-localized with SerpinB1 and bound to its promoter to trigger SerpinB1 transcription. Furthermore, LPS stimulation increased formation of neutrophil extracellular traps, which was reversed by melatonin treatment in neutrophils from WT mice, but not from KO mice. Conclusion and Implications: In mice, SerpinB1 is rhythmically regulated by Reverbα, and its down-regulation exacerbates LPS-induced ALI by inducing formation of neutrophil extracellular traps. [ABSTRACT FROM AUTHOR]

Based on the structure of the natural product cysteine, a series of thiazolidine-4-carboxylic acids were designed and synthesized. All target compounds bearing thiazolidine-4-carboxylic acid were characterized by 1H-NMR, 13C-NMR, and HRMS techniques. The antiviral and antifungal activities of cysteine and its derivatives were evaluated in vitro and in vivo. The results of anti-TMV activity revealed that all compounds exhibited moderate to excellent activities against tobacco mosaic virus (TMV) at the concentration of 500 μg/mL. The compounds cysteine (1), 3–4, 7, 10, 13, 20,23, and 24 displayed higher anti-TMV activities than the commercial plant virucide ribavirin (inhibitory rate: 40, 40, and 38% at 500 μg/mL for inactivation, curative, and protection activity in vivo, respectively), especially compound 3 (inhibitory rate: 51%, 47%, and 49% at 500 μg/mL for inactivation, curative, and protection activity in vivo, respectively) with excellent antiviral activity emerged as a new antiviral candidate. Antiviral mechanism research by TEM exhibited that compound 3 could inhibit virus assembly by aggregated the 20S protein disk. Molecular docking results revealed that compound 3 with higher antiviral activities than that of compound 24 did show stronger interaction with TMV CP. Further fungicidal activity tests against 14 kinds of phytopathogenic fungi revealed that these cysteine derivatives displayed broad-spectrum fungicidal activities. Compound 16 exhibited higher antifungal activities against Cercospora arachidicola Hori and Alternaria solani than commercial fungicides carbendazim and chlorothalonil, which emerged as a new candidate for fungicidal research.

The origin of Langerhans cells (LCs), which are skin epidermis-resident macrophages, remains unclear. Current lineage tracing of LCs largely relies on the promoter-Cre-LoxP system, which often gives rise to contradictory conclusions with different promoters. Thus, reinvestigation with an improved tracing method is necessary. Here, using a laser-mediated temporal-spatial resolved cell labeling method, we demonstrated that most adult LCs originated from the ventral wall of the dorsal aorta (VDA), an equivalent to the mouse aorta, gonads, and mesonephros (AGM), where both hematopoietic stem cells (HSCs) and non-HSC progenitors are generated. Further fine-fate mapping analysis revealed that the appearance of LCs in adult zebrafish was correlated with the development of HSCs, but not T cell progenitors. Finally, we showed that the appearance of tissue-resident macrophages in the brain, liver, heart, and gut of adult zebrafish was also correlated with HSCs. Thus, the results of our study challenged the EMP-origin theory for LCs.

This paper investigates the impact of marketing innovation on firms' participation in global value chains (GVCs) marketing activities. We test the moderating effect of international experience and technological turbulence on the relationship between firms' participation in GVCs marketing activities and firm performance, using data from 503 Chinese firms. The results highlight that firms' GVC marketing activity participation relies on marketing innovation to improve performance. Moreover, international experience strengthens the positive relationship between participation in GVCs marketing activities and firm performance. Surprisingly, the positive moderating effect is different under different levels of technological turbulence. [ABSTRACT FROM AUTHOR]