Bioactive compounds from Huashi Baidu decoction possess both antiviral and anti-inflammatory effects against COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic is an ongoing global health concern, and effective antiviral reagents are urgently needed. Traditional Chinese medicine theory-driven natural drug research and development (TCMT-NDRD) is a feasible method to address this issue as the traditional Chinese medicine formulae have been shown effective in the treatment of COVID-19. Huashi Baidu decoction (Q-14) is a clinically approved formula for COVID-19 therapy with antiviral and anti-inflammatory effects. Here, an integrative pharmacological strategy was applied to identify the antiviral and anti-inflammatory bioactive compounds from Q-14. Overall, a total of 343 chemical compounds were initially characterized, and 60 prototype compounds in Q-14 were subsequently traced in plasma using ultrahigh-performance liquid chromatography with quadrupole time-of-flight mass spectrometry. Among the 60 compounds, six compounds (magnolol, glycyrrhisoflavone, licoisoflavone A, emodin, echinatin, and quercetin) were identified showing a dose-dependent inhibition effect on the SARS-CoV-2 infection, including two inhibitors (echinatin and quercetin) of the main protease (Mpro), as well as two inhibitors (glycyrrhisoflavone and licoisoflavone A) of the RNA-dependent RNA polymerase (RdRp). Meanwhile, three anti-inflammatory components, including licochalcone B, echinatin, and glycyrrhisoflavone, were identified in a SARS-CoV-2-infected inflammatory cell model. In addition, glycyrrhisoflavone and licoisoflavone A also displayed strong inhibitory activities against cAMP-specific 3',5'-cyclic phosphodiesterase 4 (PDE4). Crystal structures of PDE4 in complex with glycyrrhisoflavone or licoisoflavone A were determined at resolutions of 1.54 Å and 1.65 Å, respectively, and both compounds bind in the active site of PDE4 with similar interactions. These findings will greatly stimulate the study of TCMT-NDRD against COVID-19.

Quadrupolar-dipolar excitonic transition in a tunnel-coupled van der Waals heterotrilayer.

Strongly bound excitons determine light-matter interactions in van der Waals heterostructures of two-dimensional semiconductors. Unlike fundamental particles, quasiparticles in condensed matter, such as excitons, can be tailored to alter their interactions and realize emergent quantum phases. Here, using a WS2/WSe2/WS2 heterotrilayer, we create a quantum superposition of oppositely oriented dipolar excitons-a quadrupolar exciton-wherein an electron is layer-hybridized in WS2 layers while the hole localizes in WSe2. In contrast to dipolar excitons, symmetric quadrupolar excitons only redshift in an out-of-plane electric field. At higher densities and a finite electric field, the nonlinear Stark shift of quadrupolar excitons becomes linear, signalling a transition to dipolar excitons resulting from exciton-exciton interactions, while at a vanishing electric field, the reduced exchange interaction suggests antiferroelectric correlations between dipolar excitons. Our results present van der Waals heterotrilayers as a field-tunable platform to engineer light-matter interactions and explore quantum phase transitions between spontaneously ordered many-exciton phases.

Juveniles, young adults, and infants with hepatitis B virus infection: A genomic study.

Integration of hepatitis B virus (HBV) DNA into the human genome is recognized as an oncogenic factor and a barrier to hepatitis B cure. In the study, biopsy liver tissues were collected from adolescents and young adults with acute HBV infection younger than or equal to 35 years of age and from HBV-infected infant patients younger than or equal to 6 months of age. A high-throughput sequencing method was used to detect HBV DNA integration. Totally, 12 adolescents, young adults, and 6 infants were included. Among the 12 patients with acute HBV infection, immunohistochemical staining of intrahepatic hepatitis B surface antigen for all displayed negative results, and no HBV DNA integrants in the hepatocyte DNA were confirmed. All infant patients had elevated levels of alanine aminotransferase and high levels of serum HBV DNA. Numerous gene sites of hepatocyte DNA were integrated by HBV DNA for each infant patient, ranging from 120 to 430 integration sites. The fragile histidine triad gene was the high-frequency integrated site in the intragenic region for infant patients. In conclusion, hepatocyte DNA is integrated by HBV DNA in babies with active hepatitis B but seems seldom affected among adolescents and young adults with acute HBV infection. Infantile hepatitis B should be taken seriously considering abundant HBV DNA integration events.

Identification and mechanism of G protein-biased ligands for chemokine receptor CCR1.

Biased signaling of G protein-coupled receptors describes an ability of different ligands that preferentially activate an alternative downstream signaling pathway. In this work, we identified and characterized different N-terminal truncations of endogenous chemokine CCL15 as balanced or biased agonists targeting CCR1, and presented three cryogenic-electron microscopy structures of the CCR1-Gi complex in the ligand-free form or bound to different CCL15 truncations with a resolution of 2.6-2.9 Å, illustrating the structural basis of natural biased signaling that initiates an inflammation response. Complemented with pharmacological and computational studies, these structures revealed it was the conformational change of Tyr291 (Y2917.43) in CCR1 that triggered its polar network rearrangement in the orthosteric binding pocket and allosterically regulated the activation of ß-arrestin signaling. Our structure of CCL15-bound CCR1 also exhibited a critical site for ligand binding distinct from many other chemokine-receptor complexes, providing new insights into the mode of chemokine recognition.

Increased Incidence of TdT-negative Pre-B Acute Lymphoblastic Leukemia Associated With Poor Prognostic Features Among Mexican Children in Central Mexico.

Mexican and Hispanic children in Mexico and the United States, respectively, have the highest incidence and worst outcomes of pre-B acute lymphoblastic leukemia (ALL) compared with other racial/ethnic groups. Terminal deoxynucleotidyl transferase (TdT) is an intranuclear DNA polymerase normally present on immature lymphocytes (TdT-positive) and distinguishes ALL from mature lymphoid malignancies. We performed a multisite retrospective study to determine the incidence of TdT-negative precursor B-cell acute lymphoblastic leukemia (pre-B ALL) among Mexican, Caucasian, and US-born Hispanic children to correlate TdT expression with patient characteristics and known prognostic factors. Fisher exact test was performed for categorical variables and the Wilcoxon rank-sum test was used for continuous variables. TdT-negative pre-B ALL was most frequently identified in patients with National Cancer Institute high-risk disease ( P =0.014). TdT-negative expression was also most frequently associated with hypodiploid pre-B ALL ( P =0.001) and KMT2A gene rearrangement ( P =0.0012). Mexican children had the highest incidence of TdT-negative ALL compared with Caucasians and US Hispanics ( P <0.001), with an increased incidence of poor prognostic features as well. This study demonstrates significant differences in TdT-negative expression, genomic alterations, and leukemic ploidy based on race and ethnicity.

Supercurrent, Multiple Andreev Reflections and Shapiro Steps in InAs Nanosheet Josephson Junctions.

We report an experimental study of proximity induced superconductivity in planar Josephson junction devices made from free-standing InAs nanosheets. The nanosheets are grown by molecular beam epitaxy, and the Josephson junction devices are fabricated by directly contacting the nanosheets with superconductor Al electrodes. The fabricated devices are explored by low-temperature carrier transport measurements. The measurements show that the devices exhibit a gate-tunable supercurrent, multiple Andreev reflections, and a good quality superconductor-semiconductor interface. The superconducting characteristics of the Josephson junctions are investigated at different magnetic fields and temperatures and are analyzed based on the Bardeen-Cooper-Schrieffer (BCS) theory. The measurements of the ac Josephson effect are also conducted under microwave radiations with different radiation powers and frequencies, and integer Shapiro steps are observed. Our work demonstrates that InAs nanosheet based hybrid devices are desired systems for investigating the forefront of physics, such as two-dimensional topological superconductivity.

Analysis of dissolved oxygen influencing factors and concentration prediction using input variable selection technique: A hybrid machine learning approach.

Accurate quantification of dissolved oxygen (DO) is critically important for the protection and management of aquatic ecosystems. Successful applications have utilized mechanistic and data-driven models to simulate DO content in aquatic ecosystems. However, mechanistic models present challenges due to their complex and difficult-to-solve conditions, making them less portable. Additionally, data-driven model predictions are hindered by the challenge of numerous input variables, impacting both the running speed and prediction performance of the model. To address these challenges, water quality data and meteorological data of the Tanjiang River were obtained. The maximum information coefficient (MIC) input variable selection technique was employed to identify primary environmental factors influencing DO changes. Furthermore, coupled with support vector regression (SVR), two models (SVR and MIC-SVR) were employed to estimate the DO concentration of the Tanjiang River, and the optimal model was established. The results indicated a shift in the primary pollution factor from ammonia nitrogen to total phosphorus after recent treatment in the Tanjiang River. In comparison with the SVR model, the root mean square error (RMSE) of the MIC-SVR model was reduced by 4.46%, and the Nash-efficiency coefficient (NSE) was improved by 45.85%. In addition, study of kernel function selection revealed that considering as many kernel functions as possible is necessary for improving the performance of the SVR model. Conclusively, the proposed MIC-SVR model serves as an effective tool to analyze the relationship between DO and environmental factors, identifying the primary causes of low DO, and accurately predict the DO concentration in the Tanjiang River (especially in its middle and lower reaches), thus providing a reference for governmental decision-making on water environmental protection and water resource management.

Characteristics and fractionations of sediment oxygen demand in a complex tidal river network area.

Tidal river networks are affected by the tide and influenced by complex factors related to sediment oxygen demand (SOD). In this study, we used chemical inhibition to measure the oxygen consumption of different types of SOD to explore the specific oxygen consumption mechanism of sediments. Then, we evaluated the diffusion fluxes of the sediment-water interface and factors affecting SOD using diffusive gradients in thin films. Total SOD in the tidal river network area of the Pearl River basin was ∼0.5928 g/m2/day, which was 8.47% higher than that in the non-tidal river network area but lower than that in black and odorous water reported previously. In the tidal river network area, biological SOD was 15.6% higher in summer than in winter, and the difference in total SOD was greatly influenced by human activity. We observed a significant effect of sediment on SOD in winter, whereas there were no significant correlations between sediment and SOD in summer. Different particle-size distributions lead to different organic matter contents, resulting in different biological SOD ratios between seasons. Our study found that seasonal tidal changes can affect ion exchange at the sediment water interface, leading to changes in SOD.These findings will be of great significance for the study of phenomena associated with low dissolved oxygen in tidal river networks and provide directions for future sediment pollution control.

[Effects of freeze-drying bovine pericardium using a combination of polyethylene glycol and trehalose].

The freeze-drying is a technology that preserves biological samples in a dry state, which is beneficial for storage, transportation, and cost saving. In this study, the bovine pericardium was treated with a freeze-drying protectant composed of polyethylene glycol (PEG) and trehalose (Tre), and then freeze-dried. The results demonstrated that the mechanical properties of the pericardium treated with PEG + 10% w/v Tre were superior to those of the pericardium fixed with glutaraldehyde (GA). The wet state water content of the rehydrated pericardium, determined using the Karl Fischer method, was (74.81 ± 1.44)%, which was comparable to that of the GA-fixed pericardium. The dry state water content was significantly reduced to (8.64 ± 1.52)%, indicating effective dehydration during the freeze-drying process. Differential scanning calorimetry (DSC) testing revealed that the thermal shrinkage temperature of the pericardium was (84.96 ± 0.49) ℃, higher than that of the GA-fixed pericardium (83.14 ± 0.11) ℃, indicating greater thermal stability. Fourier transform infrared spectroscopy (FTIR) results showed no damage to the protein structure during freeze-drying. Hematoxylin and eosin (HE) staining demonstrated that the freeze-drying process reduced pore formation, prevented ice crystal growth, and resulted in a tighter arrangement of tissue fibers. The frozen-dried bovine pericardium was subjected to tests for cell viability and hemolysis rate. The results revealed a cell proliferation rate of (77.87 ± 0.49)%, corresponding to a toxicity grade of 1. Additionally, the hemolysis rate was (0.17 ± 0.02)%, which is below the standard of 5%. These findings indicated that the frozen-dried bovine pericardium exhibited satisfactory performance in terms of cytotoxicity and hemolysis, thus meeting the relevant standards. In summary, the performance of the bovine pericardium treated with PEG + 10% w/v Tre and subjected to freeze-drying could meet the required standards.

Electric Double Layer Regulator Design through a Functional Group Assembly Strategy towards Long-Lasting Zinc Metal Batteries.

Regulating the electric double layer (EDL) structure of the zinc metal anode by using electrolyte additives is an efficient way to suppress interface side reactions and facilitate uniform zinc deposition. Nevertheless, there are no reports investigating the proactive design of EDL-regulating additives before the start of experiments. Herein, a functional group assembly strategy is proposed to design electrolyte additives for modulating the EDL, thereby realizing a long-lasting zinc metal anode. Specifically, by screening ten common functional groups, N, N-dimethyl-1H-imidazole-1-sulfonamide (IS) is designed by assembling an imidazole group, characterized by its high adsorption capability on the zinc anode, and a sulfone group, which exhibits strong binding with Zn2+ ions. Benefiting from the adsorption functionalization of the imidazole group, the IS molecules occupy the position of H2O in the inner Helmholtz layer of the EDL, forming a molecular protective layer to inhibit H2O-induced side reactions. Meanwhile, the sulfone group in IS, acting as a binding site to Zn2+, promotes the de-solvation of Zn2+ ions, facilitating compact zinc deposition. Consequently, the utilization of IS significantly extending the cycling stability of Zn||Zn and Zn||NaV3O8 ⋅ 1.5H2O full cell. This study offers an innovative approach to the design of EDL regulators for high-performance zinc metal batteries.

Synthesis of Silver Nanoparticles from Silver Closo-Dodecaborate Film for Enhanced Hydrogen Evolution.

The icosahedral closo dodecaborate cluster [B12 H12 ]2- is gaining increasing interest due to its unique properties including the ease of functionalization, 3D aromaticity, and formation of metal salts with high ion conductivity. In this work, simple and effective preparation of silver closo dodecaborte (Ag2 B12 H12 ) films is reported by an electrochemical route. The size of the Ag2 B12 H12 particles in the films can be tuned from nanometers to micrometers by varying the electrochemical parameters. Ag nanoclusters with controllable sizes are successfully generated via electrochemical reduction reactions or thermal anneal of the Ag2 B12 H12 films. When tested for hydrogen evolution reaction (HER) in an acidic solution, the as-prepared Ag nanoparticles deliver a current density of 10 mA cm-2 at 376 mV overpotential. This research sheds light on a new synthesis of [B12 H12 ]2- based thin films, the generation of metal nano-powders, and their application in HER or other applications.

Gate-tunable bolometer based on strongly coupled graphene mechanical resonators.

Bolometers based on graphene have demonstrated outstanding performance with high sensitivity and short response time. In situ adjustment of bolometers is very important in various applications, but it is still difficult to implement in many systems. Here we propose a gate-tunable bolometer based on two strongly coupled graphene nanomechanical resonators. Both resonators are exposed to the same light field, and we can measure the properties of one bolometer by directly tracking the resonance frequency shifts, and indirectly measure the other bolometer through mechanical coupling. We find that the sensitivity and the response bandwidth of both bolometers can be independently adjusted by tuning the corresponding gate voltages. Moreover, the properties of the indirectly measured bolometer show a dependence on the coupling between the two resonators, with other parameters being fixed. Our method has the potential to optimize the design of large-scale bolometer arrays, and open new horizons in infrared/terahertz astronomy and communication systems.

Impacts of 10 Years of Elevated CO2 and Warming on Soil Fungal Diversity and Network Complexity in a Chinese Paddy Field.

Climatic change conditions (elevated CO2 and warming) have been known to threaten agricultural sustainability and grain yield. Soil fungi play an important role in maintaining agroecosystem functions. However, little is known about the responses of fungal community in paddy field to elevated CO2 and warming. Herein, using internal transcribed spacer (ITS) gene amplicon sequencing and co-occurrence network methods, the responses of soil fungal community to factorial combinations of elevated CO2 (550 ppm), and canopy warming (+2 °C) were explored in an open-air field experiment for 10 years. Elevated CO2 significantly increased the operational taxonomic unit (OTU) richness and Shannon diversity of fungal communities in both rice rhizosphere and bulk soils, whereas the relative abundances of Ascomycota and Basidiomycota were significantly decreased and increased under elevated CO2, respectively. Co-occurrence network analysis showed that elevated CO2, warming, and their combination increased the network complexity and negative correlation of the fungal community in rhizosphere and bulk soils, suggesting that these factors enhanced the competition of microbial species. Warming resulted in a more complex network structure by altering topological roles and increasing the numbers of key fungal nodes. Principal coordinate analysis indicated that rice growth stages rather than elevated CO2 and warming altered soil fungal communities. Specifically, the changes in diversity and network complexity were greater at the heading and ripening stages than at the tillering stage. Furthermore, elevated CO2 and warming significantly increased the relative abundances of pathotrophic fungi and reduced those of symbiotrophic fungi in both rhizosphere and bulk soils. Overall, the results indicate that long-term CO2 exposure and warming enhance the complexity and stability of soil fungal community, potentially threatening crop health and soil functions through adverse effects on fungal community functions.

Novel role for integrin ß4 in asthmatic children infected with Mycoplasma pneumoniae.

Objectives: The regulatory role of integrin ß4 (ITGB4) in asthmatic children infected with Mycoplasma pneumoniae (MP) was analyzed, and its potential molecular mechanisms and function were studied.Methods: We collected epidemiological data from 70,455 asthmatic children. The immunofluorescence assay was used to test 9 index IgMs against respiratory tract pathogens for 736 serum samples. Then, 98 children with severe asthma were treated via fiberoptic bronchoscope examination. During the surgery, the patients' lavage fluid was collected. Additionally, differences in transforming growth factor-beta (TGF-ß) expression between the MP-infected and noninfected groups were examined. Experiments were performed using white blood cell counting methods and flow cytometry for 98 asthmatic children.Results: We tested 736 specimens, and the percentages of MP, RSV, and ADV infections were 50.27%, 11.68%, and 10.05%, respectively. The percentage of eosinophils was increased significantly in the AS-I-MP group, and their TGF-ß expression levels were increased, which was related to tissue fibrosis. Furthermore, MP infection exacerbated the decreasing trend of ITGB4 expression in patients' blood compared with the noninfected group.Conclusions: There might be a chain reaction from MP infection to an increase in ITGB4, a decrease in TGF-ß, a large accumulation of eosinophils and the development of asthma in children.

Exercise improves cognitive dysfunction and neuroinflammation in mice through Histone H3 lactylation in microglia.

BACKGROUND: Exercise is postulated to be a promising non-pharmacological intervention for the improvement of neurodegenerative disease pathology. However, the mechanism of beneficial effects of exercise on the brain remains to be further explored. In this study, we investigated the effect of an exercise-induced metabolite, lactate, on the microglia phenotype and its association with learning and memory. RESULTS: Microglia were hyperactivated in the brains of AlCl3/D-gal-treated mice, which was associated with cognitive decline. Running exercise ameliorated the hyperactivation and increased the anti-inflammatory/reparative phenotype of microglia and improved cognition. Mice were injected intraperitoneally with sodium lactate (NaLA) had similar beneficial effects as that of exercise training. Exogenous NaLA addition to cultured BV2 cells promoted their transition from a pro-inflammatory to a reparative phenotype. CONCLUSION: The elevated lactate acted as an "accelerator" of the endogenous "lactate timer" in microglia promoting this transition of microglia polarization balance through lactylation. These findings demonstrate that exercise-induced lactate accelerates the phenotypic transition of microglia, which plays a key role in reducing neuroinflammation and improving cognitive function.

First report of leaf spot disease caused by Alternaria alternata in Tilia miqueliana in Jiangsu Province, China.

Tilia miqueliana Maxim., a tall deciduous tree in the Malvaceae family, is native to china and is cultivated in the Jiangsu, Zhejiang, Anhui, and Jiangxi provinces as an ornamental plant. T. miqueliana has currently received increased attention because of its value as timber, a source plant for honey, and in formal landscape architecture (Wang et al. 2022). In the last three years, symptoms of leaf spot disease were observed in T. miqueliana fields （9-year-old tree）and a breeding nursery _(1-year-old saplings) in Nanjing, Jiangsu Province, China. Field surveys showed that, the disease incidence was approximately 10% and 40% in the fields and breeding nursery, respectively. Symptoms of leaf spot disease on T. miqueliana appeared as small, circular, or near-circular/irregular black lesions on the upper surfaces of the leaves. As the disease progressed, the spots expanded into irregular shapes with the center turning yellow to black and leaves wilted from margins to centers. In severe cases, the yellow necrotic area extended to the margin, which ultimately led to leaf curling and death. To analyze the presence of the pathogenic microorganism, pieces of leaf at the junction of diseased and healthy tissue (about 3x3 mm) were taken from symptomatic plants, sterilized with 75% ethanol for 1 min and 2% sodium hypochlorite (NaClO) for 2 min, and washed 3 times with ddH2O. The leaf pieces were transferred onto Potato Dextrose Agar (PDA) plates and incubated at 28°C for 3 days in the dark. Colonies were observed and transferred to fresh PDA plates. Sixteen fungal isolates were obtained and one (named D4-2) of them was verified using Koch's assumption. Single spores of D4-2 were cultured in PDA medium, while its initial colony morphology was fluffy white colonies, which then gradually turned dark yellow from the centre to the edge. To further analyze the form of the spores, a hypha was incubated on fresh synthetic low-nutrient agar (SNA) using cellophane and inverted cultivation was performed for 20 days in the dark. Obclavate or obpyriform conidia (10 to 30 × 2 to 18 µm, n=5) were produced in chains and were pale brown to brown in color. The morphology was consistent with that of Alternaria sp.. The molecular identification of the isolated representative fungus D4-2 was conducted via the amplification of the internal transcribed spacer (ITS) (White et al. 1990),translation elongation factor 1 alpha (TEF) (Carbone and Kohn. 1999), glyceraldehyde-3-dehydrogenase (GAPDH) (Berbee et al. 1999) and RNA polymerase II beta subunit (RPB2) using the primer pairs ITS1/ITS4, EF1-728F/EF1-986R, GPD1/GPD2, and RPB2-5F2/fRPB2-7cR (Sung et al. 2007) respectively. All these sequences were deposited in GenBank under accession numbers OP108438 (ITS), OP168372 (RPB2), OQ473880 (TEF), and OP168374 (GAPDH). Based on the GAPDH, RPB2, and TEF regions of D4-2, MEGA-11 was used to construct a neighbor-joining tree (1000 replications) with 31 other known species that had a relatively close evolutionary relationship with species from the Alternaria genus (Woudenberg et al. 2013). The phylogenetic tree indicated 100% bootstrap support between D4-2 and A. alternata. The branches showing the distribution of other species were exactly the same as that of the consensus tree based on the Bayesian 50 % majority rule that represented the Alternaria-complex (Woudenberg et al. 2013). The initial Koch's Postulates was verified using PDA slices with mycelium (pure PDA slices were used as control) that were inverted on the leaves at 25℃ for 3 days before removing slices and observing the phenotype after 7 days. Only leaves infected with D4-2 showed the same symptoms. Moreover, the spore suspension (at a concentration of 107 spores/mL) of D4-2 was applied to the leaves of T. miqueliana seedlings. After 15 days of incubation at 26 ℃ , the leaves showed the same symptoms. Subsequently, the pathogen was reisolated and cultured from these invaded leaves using the same method described above. Morphological and molecular identifications were consistent with those of D4-2. Above all, the pathogenic fungus (D4-2) isolated from T. miqueliana leaves was confirmed to be A. alternata. T. miqueliana is considered to be an endangered species due to the deep dormancy of its seeds that result in a low natural germination rate (Wu and Shen. 2021). At present, research on T. miqueliana mainly focuses on seed germination and breeding technology, and there is hardly any research on the diseases occurring in T. miqueliana. Therefore, we believe that this is the first report of leaf spot disease caused by A. alternata on T. miqueliana in China.

Lightweight Model for Pavement Defect Detection Based on Improved YOLOv7.

Existing pavement defect detection models face challenges in balancing detection accuracy and speed while being constrained by large parameter sizes, hindering deployment on edge terminal devices with limited computing resources. To address these issues, this paper proposes a lightweight pavement defect detection model based on an improved YOLOv7 architecture. The model introduces four key enhancements: first, the incorporation of the SPPCSPC_Group grouped space pyramid pooling module to reduce the parameter load and computational complexity; second, the utilization of the K-means clustering algorithm for generating anchors, accelerating model convergence; third, the integration of the Ghost Conv module, enhancing feature extraction while minimizing the parameters and calculations; fourth, introduction of the CBAM convolution module to enrich the semantic information in the last layer of the backbone network. The experimental results demonstrate that the improved model achieved an average accuracy of 91%, and the accuracy in detecting broken plates and repaired models increased by 9% and 8%, respectively, compared to the original model. Moreover, the improved model exhibited reductions of 14.4% and 29.3% in the calculations and parameters, respectively, and a 29.1% decrease in the model size, resulting in an impressive 80 FPS (frames per second). The enhanced YOLOv7 successfully balances parameter reduction and computation while maintaining high accuracy, making it a more suitable choice for pavement defect detection compared with other algorithms.

Mechanism Repositioning Based on Integrative Pharmacology: Anti-Inflammatory Effect of Safflower in Myocardial Ischemia-Reperfusion Injury.

Safflower (Carthamus tinctorius. L) possesses anti-tumor, anti-thrombotic, anti-oxidative, immunoregulatory, and cardio-cerebral protective effects. It is used clinically for the treatment of cardio-cerebrovascular disease in China. This study aimed to investigate the effects and mechanisms of action of safflower extract on myocardial ischemia-reperfusion (MIR) injury in a left anterior descending (LAD)-ligated model based on integrative pharmacology study and ultra-performance liquid chromatography-quadrupole time-of-flight-tandem mass spectrometer (UPLC-QTOF-MS/MS). Safflower (62.5, 125, 250 mg/kg) was administered immediately before reperfusion. Triphenyl tetrazolium chloride (TTC)/Evans blue, echocardiography, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay, lactate dehydrogenase (LDH) ability, and superoxide dismutase (SOD) levels were determined after 24 h of reperfusion. Chemical components were obtained using UPLC-QTOF-MS/MS. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were used to analyze mRNA and protein levels, respectively. Safflower dose-dependently reduced myocardial infarct size, improved cardiac function, decreased LDH levels, and increased SOD levels in C57/BL6 mice. A total of 11 key components and 31 hub targets were filtered based on the network analysis. Comprehensive analysis indicated that safflower alleviated inflammatory effects by downregulating the expression of NFκB1, IL-6, IL-1ß, IL-18, TNFα, and MCP-1 and upregulating NFκBia, and markedly increased the expression of phosphorylated PI3K, AKT, PKC, and ERK/2, HIF1α, VEGFA, and BCL2, and decreased the level of BAX and phosphorylated p65. Safflower shows a significant cardioprotective effect by activating multiple inflammation-related signaling pathways, including the NFκB, HIF-1α, MAPK, TNF, and PI3K/AKT signaling pathways. These findings provide valuable insights into the clinical applications of safflower.

Differentiation of Mountain- and Garden-Cultivated Ginseng with Different Growth Years Using HS-SPME-GC-MS Coupled with Chemometrics.

Although there are differences in the appearance of Mountain-Cultivated Ginseng (MCG) and Garden-Cultivated Ginseng (GCG), it is very difficult to distinguish them when the samples are processed to slices or powder. Moreover, there is significant price difference between them, which leads to the widespread adulteration or falsification in the market. Thus, the authentication of MCG and GCG is crucial for the effectiveness, safety, and quality stability of ginseng. In the present study, a headspace solid-phase microextraction gas chromatography mass spectrometry (HS-SPME-GC-MS) coupled with chemometrics approach was developed to characterize the volatile component profiles in MCG and GCG with 5-,10-,15-growth years, and subsequently to discover differentiating chemical markers. As a result, we characterized, for the first time, 46 volatile components from all the samples by using the NIST database and the Wiley library. The base peak intensity chromatograms were subjected to multivariate statistical analysis to comprehensively compare the chemical differences among the above samples. MCG5-,10-,15-years and GCG5-,10-,15-years samples were mainly divided into two groups by unsupervised principal component analysis (PCA), and 5 potential cultivation-dependent markers were discovered based on orthogonal partial least squares-discriminant analysis (OPLS-DA). Moreover, MCG5-,10-,15-years samples were divided into three blocks, and 12 potential growth-year-dependent markers enabled differentiation. Similarly, GCG5-,10-,15-years samples were also separated into three groups, and six potential growth-year-dependent markers were determined. The proposed approach could be applied to directly distinguish MCG and GCG with different growth years and to identify the differentiation chemo-markers, which is an important criterion for evaluating the effectiveness, safety, and quality stability of ginseng.

[Mechanism of Mongolian drug Naru-3 in initiation of neuroinflammation of neuropathic pain from MMP9/IL-1ß signaling pathway].

Neuropathic pain(NP) has similar phenotypes but different sequential neuroinflammatory mechanisms in the pathological process. It is of great significance to inhibit the initiation of neuroinflammation, which has become a new direction of NP treatment and drug development in recent years. Mongolian drug Naru-3 is clinically effective in the treatment of trigeminal neuralgia, sciatica, and other NPs in a short time, but its pharmacodynamic characteristics and mechanism of analgesia are still unclear. In this study, a spinal nerve ligation(SNL) model simulating clinical peripheral nerve injury was established and the efficacy and mechanism of Naru-3 in the treatment of NPs was discussed by means of behavioral detection, side effect evaluation, network analysis, and experimental verification. Pharmacodynamic results showed that Naru-3 increased the basic pain sensitivity threshold(mechanical hyperalgesia and thermal radiation hyperalgesia) in the initiation of SNL in animals and relieved spontaneous pain, however, there was no significant effect on the basic pain sensitivity threshold and motor coordination function of normal animals under physiological and pathological conditions. Meanwhile, the results of primary screening of target tissues showed that Naru-3 inhibited the second phase of injury-induced nociceptive response of formalin test in mice and reduced the expression of inflammatory factors in the spinal cord. Network analysis discovered that Naru-3 had synergy in the treatment of NP, and its mechanism was associated with core targets such as matrix metalloproteinase-9(MMP9) and interleukin-1ß(IL-1ß). The experiment further took the dorsal root ganglion(DRG) and the stage of patho-logical spinal cord as the research objects, focusing on the core targets of inducing microglial neuroinflammation. By means of Western blot, immunofluorescence, agonists, antagonists, behavior, etc., the mechanism of Naru-3 in exerting NP analgesia may be related to the negative regulation of the MMP9/IL-1ß signaling pathway-mediated microglia p38/IL-1ß inflammatory loop in the activation phase. The relevant research enriches the biological connotation of Naru-3 in the treatment of NP and provides references for clinical rational drug use.