Enhancing the Safety and Efficacy of Trastuzumab Emtansine (T-DM1) Through Nano-Delivery System in Breast Cancer Therapy.

Trastuzumab emtansine (T-DM1), an antibody-drug conjugate, revolutionizes breast cancer therapy by specifically delivering DM1 to human epidermal growth factor receptor 2 (HER2) overexpressing tumor cells, effectively inhibiting cell division and proliferation. While T-DM1 demonstrates superior efficacy and tolerability, T-DM1-induced thrombocytopenia remains a significant adverse event leading to treatment discontinuation. To address this issue, the study investigates the feasibility of using poly(lactic-co-glycolic acid) (PLGA) nanoparticles as a delivery vehicle to conjugate T-DM1, aiming to alleviate T-DM1-induced thrombocytopenia. The T-DM1-conjugated PLGA nanoparticles (NPs-T-DM1) reduce binding to megakaryocytes without compromising the targeting ability for HER2. Administration of NPs-T-DM1 not only significantly inhibits tumor growth but also reduces damage to megakaryocytes, inhibits T-DM1-induced thrombocytopenia, and remarkably improves the safety of antibody-conjugated drugs. This work presents a promising strategy to enhance the safety and efficacy of T-DM1 in antitumor therapy, offering significant potential for advancing clinical application in HER2-positive breast cancer patients.

Coexistence and genomics characterization of mcr-1 and extended-spectrum-ß-lactamase-producing Escherichia coli, an emerging extensively drug-resistant bacteria from sheep in China.

The emergence of pathogens harboring multiple resistance genes poses a great threat to global public health. However, the coexistence of mobile resistance genes that provide resistance to both third-generation cephalosporins and colistin in sheep-origin Escherichia coli has not been previously investigated in China. This study is the first to characterize five E. coli isolates from sheep in Shaanxi province that harbor both Extended-Spectrum ß-Lactamase (ESBL) and mcr-1 resistance genes. The isolates were identified and characterized by Illumina sequencing, nanopore sequencing, bioinformatic analysis, conjugation experiments, and antimicrobial susceptibility testing. Genetic analysis revealed that blaCTX-M-55 gene, mediated by the IS26, was located on the IncFIB-IncFIC plasmid, while the mcr-1 gene was located on the IncI2(Delta) plasmid. Notably, two copies of blaCTX-M-55 gene were also identified on the chromosome of one isolate (SX45), facilitated by the ISEcp1 insertion sequence. Additionally, the plasmid pSX23-2 was identified as a complex plasmid derived through homologous recombination of pMG337 from E. coli (MK878890) and pZY-1 from Citrobacter freundii (CP055248). Data mining of publicly available databases revealed that isolates carrying both blaCTX-M-55 and mcr-1 genes have been found in humans, animals, and the environment, indicating the widespread presence of these critical resistance genes across different niches. Antimicrobial susceptibility testing showed that the five isolates were resistant to a nearly all tested antibiotics, except meropenem. Conjugative transfer experiments demonstrated that the IncFIB-IncFIC and IncI2(Delta) plasmids carrying mcr-1 and blaCTX-M-55 were capable of transferring between different sequence types (STs) of sheep-origin E. coli, including ST10, ST162, and ST457. This finding suggests the potential for wide dissemination of these resistance markers among diverse E. coli strains. Overall, the characterization of these ESBL and mcr-1 co-harboring isolates enhances our understanding of the spread of these resistance genes in sheep-origin E. coli. Global surveillance of these isolates, particularly within the One Health framework, is essential to monitor and mitigate the risks posed by the dissemination of these resistance genes across various settings.

Efficacy of immediate loading compared to conventional loading in implant-supported removable prostheses: a systematic review and meta-analysis.

PURPOSE: This systematic review and meta-analysis aimed to evaluate the efficacy of two different loading methods in implant-supported removable prostheses (partial dentures and full-maxillary dentures). METHODS: As of August 2023, three electronic databases and nine oral implant-related journals had been searched. Only randomised controlled trials (RCTs) that compare immediate loading with conventional loading in implant-supported removable prostheses were included. The primary outcome was the implant survival rate. At the same time, a meta-analysis of bone-level changes was performed. Cochrane risk-of-bias tool for randomised trials (RoB 2) was used to evaluate the risk of bias in the included trials. RESULTS: A total of 16 RCTs were included, including 543 participants with 1595 implants. The included trials compared immediate loading and conventional loading in implant-supported removable prostheses. Regarding implants as the statistical unit, the immediate loading group had a statistically significant lower survival rate (RR = 0.950; 95% confidence interval [CI], (0.926, 0.974); P = 0.027; I² = 47%). When patients were regarded as statistical units, a statistically significant lower survival rate was also observed in the immediate loading group (RR = 0.929; 95% CI, (0.897, 0.961); P = 0.590; I² = 0%). When we analysed the bone level changes, a statistically significant decrease was observed in bone level in the immediate loading group compared with the conventional loading group (weighted mean difference [WMD] = -0.127; 95% CI, (-0.195, -0.059); P < 0.00001). CONCLUSION: Lower implant survival rates and a decrease in marginal bone level was observed compared to immediate loading with conventional loading.

Establishing a Risk Model for Diabetic Nephropathy and Addressing the Therapeutic Effect of Combined Epalrestat- Dapagliflozin Regimen.

INTRODUCTION: To explore the construction of a diagnostic prediction model of diabetic nephropathy (DN) in type 2 diabetic patients for prognostic risk prediction and observe the therapeutic effect of Epalrestat combined with Dapagliflozin on DN. METHODS: The study consisted of two phases, phase I: A retrospective analysis was conducted on the case information and clinical treatment related data of a total of 460 patients who underwent kidney biopsy from June 2018 to June 2021. They were randomly divided into validation queue and training queue. The predictive factors of the diagnostic prediction model were obtained through multivariate logistic regression. PHASE II: An interventional study of 94 patients with DN admitted between January 2022 and August 2023 was conducted, and they were randomized into a control group (n = 47) receiving Dapagliflozin and a research group (n = 47) receiving Epalrestat combined with Dapagliflozin. The glucose metabolism, renal function, and treatment safety of the two groups before and after treatment were compared. In addition, the adverse reactions during the treatment of the two groups were counted. RESULTS: In the phase I of the study, the DN risk model established showed a good performance in the diagnosis and risk assessment of patients with DN and could provide certain reference opinions for future clinical practice. In the phase II of the study, the research group showed better glucose metabolism and renal function than the control group after treatment (P < .05), but no statistical difference was identified between groups in the incidence of adverse reactions (P > .05).  Conclusion. Epalrestat combined with Dapagliflozin is significantly effective in the treatment of DN, which can effectively improve glucose metabolism and renal function in DN patients.

Comparison of depressive symptoms among emergency physicians and the general population in China: a cross-sectional study based on national data.

BACKGROUND: While physicians are considered to be more susceptible to developing depressive symptoms, empirical data are lacking. The study aims to compare the risk of depressive symptoms between emergency physicians and the general population in China based on national data. METHODS: This was a national cross-sectional study. 10 457 emergency physicians and 101 120 participants from the general population were investigated from July 2018 to August 2018 and January 2019 to February 2019, respectively. PHQ-9 was used to measure depressive symptoms, and a score ≥ 10 indicates major depression. Propensity score matching was adopted to balance the characteristics between emergency physicians and the general population. Multinomial logistic regression model was used to examine the association between occupational groups and the severity of depressive symptoms. Binary logistic regression model was performed to explore the risk factors of major depression among emergency physicians. RESULTS: The prevalence of major depression among emergency physicians was 35.7%, whereas among the general population was 13.9%. Emergency physicians had a 3.65 times higher risk of major depression than the general population. And emergency physician was significantly associated with mild (OR: 3.12, 95% CI 2.95-3.30), moderate (OR: 4.94, 95% CI 4.60-5.30), moderately severe (OR: 9.48, 95% CI 8.61-10.44), and severe depressive symptoms (OR: 14.18, 95% CI 12.47-16.13) compared with none depressive symptoms. Even after matching, the results remained consistent. Factors associated with major depression among emergency physicians included bachelor degree or above (OR: 1.22, 95% CI 1.06-1.40), worked long years (OR: 1.26, 95% CI 1.08-1.46 for 1-5 years; OR: 1.56, 95% CI 1.32-1.84 for ≥ 6 years), experienced workplace violence (OR: 2.51, 95% CI 2.16-2.94), worked more night shifts per month (OR: 1.33, 95% CI 1.16-1.51 for 6-10 times; OR: 1.83, 95% CI 1.58-2.11 for ≥ 11 times), smoked (OR: 1.64, 95% CI 1.47-1.84), and effort-reward imbalance (OR: 4.18, 95% CI 3.62-4.85). CONCLUSIONS: Emergency physicians had a higher risk of depressive symptoms than the general population. There is a need for greater awareness of the mental health issues faced by emergency physicians.

Identification of a Novel Parvovirus in the Arctic Wolf (Canis lupus arctos).

A novel virus, temporarily named "Arctic wolf parvovirus" (AWPV), was discovered in a pharyngeal metagenomic library derived from an Arctic wolf (Canis lupus arctos) in China. The genome sequence was assigned GenBase accession number C_AA071902.1. AWPV has a genome comprised of 4,920 base pairs with a nucleotide composition of 36.4% A, 23.4% T, 18.2% G, and 22.0% C, with a GC content of 40.2%. Its structure resembles parvoviruses, containing two open reading frames: the nonstructural (NS) region encoding replication enzymes and the structural (VP) region encoding capsid protein. Pairwise sequence comparison and phylogenetic analysis suggest AWPV may represent a novel species within the genus Protoparvovirus. This discovery enhances our understanding of mammalian virus ecology and potential future infectious diseases.

Nine months of bedaquiline, linezolid, levofloxacin, clofazimine, and cycloserine chemotherapy for rifampicin/multidrug-resistant tuberculosis: a multicenter, randomized, open-label non-inferiority trial in China.

BACKGROUND: We concurrently developed a prospective study to assess clinical outcomes among patients receiving 9-month bedaquiline (BDQ)-containing regimens, aiming to provide valuable data on the use of this short-course regimen in China. METHODS: This open-label, randomized, controlled, multicenter, non-inferiority trial was conducted at sixteen hospitals, and enrolled participants aged 18 years and older with pulmonary rifampicin/multidrug tuberculosis. Participants were randomly assigned, in a 1:1 ratio. Individuals within the standard-regimen group received 6 months of BDQ, linezolid, levofloxacin, clofazimine, and cycloserine plus 12 months of levofloxacin, and any three potentially effective drugs from clofazimine, cycloserine pyrazinamide, ethambutol and protionamide, whereas individuals within shorter-regimen group received 9 months of BDQ, linezolid, levofloxacin, clofazimine and cycloserine. The primary outcome was the percentage of participants with a composite unfavorable outcome (treatment failure, death, treatment discontinuation, or loss to follow-up) by the end of the treatment course after randomization in the modified intention-to-treat population. The noninferiority margin was 10%. This trial was registered with www.chictr.org.cn , ChiCTR2000029012. RESULTS: Between Jan 1, 2020, and Dec 31, 2023, 264 were screened and randomly assigned, 132 of 264 participants were assigned to the standard-regimen group and 132 were assigned to the shorter-regimen. Thirty-three (12.55%) of 264 participants were excluded from the modified intention-to-treat analysis. As a result, 231 participants were included in the modified intention-to-treat analysis (116 in the standard-regimen group and 115 in the shorter-regimen group).In the modified intention-to-treat population, unfavorable outcomes were reported in 19 (16.5%) of 115 participants for whom the outcome was assessable in the shorter-regimen group and 26 (22.4%) of 116 participants in the standard care group (risk difference 5.9 percentage points (97.5% CI - 5.8 to 17.5)). One death was reported in the standard-regimen group. The incidence of QTcF prolongation in the shorter-regimen group (22.6%, 26/115) was similar to the standard-regimen group (24.1%, 28/116). CONCLUSIONS: The 9-month, all-oral regimen is safe and efficacious for the treatment of pulmonary rifampicin/multidrug-resistant tuberculosis. The high incidence of QTc prolongation associated with the use of BDQ highlights the urgent need of routine electrocardiogram monitoring under treatment with BDQ-containing regimens in the Chinese population.

The effects of physical activity on adolescents' depression: evidence from China.

Background: Depression is becoming a common threat to the mental health of Chinese adolescents. As an intermediate stage between being healthy and having depression, identifying factors influencing depressive may contribute to providing more options for the prevention and treatment of depression. Objective: The study aims to explore the effects of physical activity on adolescent depression, focusing on the times and hours of activity per week. Methods: The study used a cross-sectional dataset collected in Ruyang County, Henan Province in September 2022, including a sample of 5,629 adolescents in 31 compulsory public schools in the county. We utilized Ordinary Least Squares (OLS) to analyze the impact of physical activity on adolescents' depression scores, and probit model to analyze the influence of physical activity on adolescents' depression. To examine whether there is a U-shaped relationship between physical activity and depression, we included the squared terms of times and hours of activity in models. Results: The results showed that: (1) The times of physical activity significantly reduces Chinese adolescent depression. An increase in physical activity by one time per week is associated with a mean decrease of 0.354 points in depression scores (p < 0.01). However, an increase of one time of physical activity per week is associated with an average 1% increase in the likelihood of experiencing depression(p < 0.05), while the hours of physical activity was statistically insignificant. (2) Physical activity has a U-shaped (not linear) relationship with adolescent depression, with 7-8 times per week or 7-9 h of physical activity per week being the optimal range. Conclusion: The study found that increasing the frequency of physical activity positively impacts adolescent depression, while increasing the hours does not show a significant association. Furthermore, a U-shaped relationship exists between times of activity, hours of activity, and adolescent depression, suggesting that moderate activity is optimal.

Development of the first officially licensed live attenuated duck hepatitis A virus type 3 vaccine strain HB80 in China and its protective efficacy against DHAV-3 infection in ducks.

Duck hepatitis A virus type 3 (DHAV-3) is an infectious virus that is highly fatal to ducklings and causes significant economic losses in the duck industry worldwide. Biosecurity and vaccination are required to control the pathogen. In the present study, we attenuated a lowly pathogenic DHAV-3 clinical isolate, named as HB, by serial passaging in duck embryos, and followed by several adaptive proliferations in specific-pathogen-free (SPF) chicken embryos. The virulence of DHAV-3 at different passages was assessed by infecting 3-day-old ducklings. We found that the HB strain lost pathogenicity to ducklings from the 55th passage onwards. The 80th passage strain (HB80), which achieved good growth capacity in duck embryos with a viral titer of 108.17 50% egg lethal dose per milliliter (ELD50/mL), was selected as a live attenuated vaccine candidate. The HB80 strain did not induce clinical symptoms or pathological lesions in 3-day-old ducklings and showed no virulence reversion after 5 rounds of in vivo back-passage. The minimum effective dose of HB80 was determined to be 104.5 ELD50 by hypodermic inoculation of the neck. Importantly, a single dose of HB80 elicited good immune responses and provided complete protection against challenge with the lethal DHAV-3 strain. Compared with the genomic sequence of the parental HB strain, HB80 had 7 amino acid substitutions, two of them are in the hypervariable region of the VP1 and polymerase-encoding 3D regions, which may play a role in virulence attenuation. Our data suggest that the attenuated HB80 strain is a promising vaccine candidate for the prevention of DHAV-3 infections in China. HB80 has been registered as a New Veterinary Drug Registration Certificate by the Chinese Ministry of Agriculture and Rural Affairs (MARA), and is the first live attenuated DHAV-3 vaccine strain to be officially licensed in China.

Experimental and computational aspects of molecular frustrated Lewis pairs for CO2 hydrogenation: en route for heterogeneous systems?

Catalysis plays a crucial role in advancing sustainability. The unique reactivity of frustrated Lewis pairs (FLPs) is driving an ever-growing interest in the transition metal-free transformation of small molecules like CO2 into valuable products. In this area, there is a recent growing incentive to heterogenize molecular FLPs into porous solids, merging the benefits of homogeneous and heterogeneous catalysis - high activity, selectivity, and recyclability. Despite the progress, challenges remain in preventing deactivation, poisoning, and simplifying catalyst-product separation. This review explores the expanding field of FLPs in catalysis, covering existing molecular FLPs for CO2 hydrogenation and recent efforts to design heterogeneous porous systems from both experimental and theoretical perspectives. Section 2 discusses experimental examples of CO2 hydrogenation by molecular FLPs, starting with stoichiometric reactions and advancing to catalytic ones. It then examines attempts to immobilize FLPs in porous matrices, including siliceous solids, metal-organic frameworks (MOFs), covalent organic frameworks, and disordered polymers, highlighting current limitations and challenges. Section 3 then reviews computational studies on the mechanistic details of CO2 hydrogenation, focusing on H2 splitting and hydride/proton transfer steps, summarizing efforts to establish structure-activity relationships. It also covers the computational aspects on grafting FLPs inside MOFs. Finally, Section 4 summarizes the main design principles established so far, while addressing the complexities of translating computational approaches into the experimental realm, particularly in heterogeneous systems. This section underscores the need to strengthen the dialogue between theoretical and experimental approaches in this field.

[Spatiotemporal Evolution Characteristics of Carbon Sources and Carbon Sinks and Carbon Balance Zoning in the Yangtze River Delta Region].

Mastering the spatiotemporal evolution laws of carbon sources and sinks is of great significance to promote the coordinated development of regional low-carbon, improve the science of carbon reduction and sink increase policies, and realize the goal of "double carbon." Taking 41 cities in the Yangtze River Delta Region as the research object, this study analyzed the spatiotemporal evolution characteristics of carbon sources and sinks in the Yangtze River Delta Region from 2000 to 2020 and conducted the carbon balance zoning. The results were as follows： ① The carbon emissions increased rapidly in the Yangtze River Delta Region from 2000 to 2011 but with some fluctuations after 2011. Carbon sinks increased slowly in the Yangtze River Delta Region from 2000 to 2020. The regional differences in carbon emissions and carbon sinks were significant, and the spatial pattern was relatively stable. ② The carbon compensation rate in the Yangtze River Delta Region showed a downward trend, and the carbon productivity, energy utilization efficiency, and carbon ecological support capacity were constantly enhanced. Interregional differences were the main source of carbon compensation rate in the Yangtze River Delta Region. Both the carbon compensation rate and carbon ecological support coefficient showed a spatial pattern of "high in the west and low in the east, high in the south and low in the north." The areas with high carbon economy contributive coefficient were concentrated in the central and southern areas of the Yangtze River Delta regions, and the areas with low carbon economy contributive coefficient were concentrated in Anhui Province. ③ Based on the carbon economy contributive coefficient and the carbon ecological support coefficient, cities in the Yangtze River Delta Region were classified into low-carbon maintenance areas, economic development areas, carbon sink development areas, and comprehensive optimization areas. Recommendations were proposed for each category of cities in order to promote the coordinated development of regional low-carbon and realize the goal of "double carbon".

DWARF AND LESS TILLERS ON CHROMOSOME 3 promotes tillering in rice by sustaining FLORAL ORGAN NUMBER 1 expression.

Three key factors determine yield in rice (Oryza sativa): panicle number, grain number, and grain weight. Panicle number is strongly associated with tiller number. Although many genes regulating tillering have been identified, whether Dof proteins are involved in controlling plant architecture remains unknown. The dwarf and less tillers on chromosome 3 (dlt3) rice mutant produces fewer tillers than the wild type. We cloned DLT3, which encodes a Dof protein that interacts with MONOCULM 3 (MOC3) in vivo and in vitro and recruits MOC1, forming a DLT3-MOC3-MOC1 complex. DLT3 binds to the promoter of FLORAL ORGAN NUMBER 1 (FON1) to activate its transcription and positively regulate tiller number. The overexpression of MOC1, MOC3, or FON1 in the dlt3 mutant increased tiller number. Collectively, these results suggest a model in which DLT3 regulates tiller number by maintaining the expression of MOC1, MOC3, and FON1. We discovered that DLT3 underwent directional selection in the Xian/indica and Geng/japonica populations during rice domestication. To provide genetic resources for breeding varieties with optimal panicle numbers, we performed large-scale diversity sequencing of the 1,080-bp DLT3 coding region of 531 accessions from different countries and regions. Haplotype analysis showed that the superior haplotype, DLT3H1, produced the most tillers, while haplotype DLT3H6 produced the fewest tillers. Our study provides important germplasm resources for breeding super high-yielding rice varieties with combinations of superior haplotypes in different target genes, which will help overcome the challenge of food and nutritional security in the future.

Correlation between serum sex hormone-binding globulin levels and nutrition indicators and malnutrition exposure risk in men and postmenopausal women with type 2 diabetes.

BACKGROUND: This study sought to investigate the correlation between serum sex hormone-binding globulin (SHBG) levels and nutrition indicators and the malnutrition exposure risk in men and postmenopausal women with type 2 diabetes mellitus (T2DM). METHODS: A cross-sectional analysis was conducted, involving patients diagnosed with T2DM at the Guangdong Provincial People's Hospital between May 2018 and December 2019. RESULTS: The study comprised 551 participants (363 men, mean age of 55.55 ± 11.57 years), among whom 167 (30.31%) were classified as with malnutrition exposure risk (GNRI ≤ 98). Multivariable logistic regression analysis revealed that SHBG (OR = 1.04, 95% CI: 1.02-1.05, P < 0.001), glycated hemoglobin (OR = 1.36, 95% CI: 1.22-1.51, P < 0.001), hemoglobin (OR = 0.96, 95% CI: 0.94-0.97, P < 0.001), and non-alcoholic fatty liver disease (OR = 0.41, 95% CI: 0.23-0.73, P < 0.003) were independently associated with the malnutrition exposure risk. SHBG was inversely correlated with body mass index (males: r = -0.34; postmenopausal females: r = -0.22), albumin (males: r = -0.30; postmenopausal females: r = -0.20), transferrin (males: r = -0.28; postmenopausal females: r = -0.19), and prealbumin (males: r = -0.35; postmenopausal females: r = -0.30) (all P < 0.05). CONCLUSIONS: Serum SHBG levels are correlated with nutritional indicators and the risk of malnutrition in men and postmenopausal women with T2DM. A multicenter prospective study is imperative to verify this result in the future.

Medicinal Plant Root Exudate Metabolites Shape the Rhizosphere Microbiota.

The interactions between plants and rhizosphere microbes mediated by plant root exudates are increasingly being investigated. The root-derived metabolites of medicinal plants are relatively diverse and have unique characteristics. However, whether medicinal plants influence their rhizosphere microbial community remains unknown. How medicinal plant species drive rhizosphere microbial community changes should be clarified. In this study involving high-throughput sequencing of rhizosphere microbes and an analysis of root exudates using a gas chromatograph coupled with a time-of-flight mass spectrometer, we revealed that the root exudate metabolites and microorganisms differed among the rhizosphere soils of five medicinal plants. Moreover, the results of a correlation analysis indicated that bacterial and fungal profiles in the rhizosphere soils of the five medicinal plants were extremely significantly or significantly affected by 10 root-associated metabolites. Furthermore, among the 10 root exudate metabolites, two (carvone and zymosterol) had opposite effects on rhizosphere bacteria and fungi. Our study findings suggest that plant-derived exudates modulate changes to rhizosphere microbial communities.

Correction: Chen et al. HP3D-V2V: High-Precision 3D Object Detection Vehicle-to-Vehicle Cooperative Perception Algorithm. Sensors 2024, 24, 2170.

In the original publication [...].

A synergistic mechanism of Liquiritin and Licochalcone B from Glycyrrhiza uralensis against COPD.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is a refractory respiratory disease mainly attributed to multiple pathological factors such as oxidative stress, infectious inflammation, and idiopathic fibrosis for decades. The medicinal plant Glycyrrhiza uralensis extract (ULE) was widely used to control respiratory diseases in China. However, the regulatory mechanism of scientific evidence to support the therapeutic benefits of ULE in the management of COPD is greatly limited. PURPOSE: This study aims to discover the potential protection mechanism of ULE on COPD via a muti-targets strategy. STUDY DESIGN AND METHODS: The present study set out to determine the potential protective effects of ULE on COPD through a multi-target strategy. In vivo and in vitro models of COPD were established using cigarette smoke and lipopolysaccharide to assess the protective effects of ULE. It was evaluated by measuring inflammatory cytokines and assessing pulmonary pathological changes. HPLC was used to verify the active compounds of the potential compounds that were collected and screened using HERB, works of literature, and ADME tools. The mechanisms of ULE in the treatment of COPD were explored using transcriptomics, connectivity-map, and network pharmacology approaches. The relevant targets were further investigated using RT-PCR, western blot, and immunohistochemistry. The HCK inhibitor (iHCK-37) was used to evaluate the potential mechanism of ULE's active compounds in the prevention of COPD. RESULTS: ULE effectively protected the lungs of COPD mice from oxidative stress, inflammation, and fibrosis damage. After screening and verification using ADME properties and HPLC, 4 active compounds were identified in ULE: liquiritin (LQ), licochalcone B (LCB), licochalcone A (LCA), and echinatin (ET). Network pharmacology integrated with transcriptomics analysis showed that ULE mitigated oxidative stress, inflammation, and fibrosis in COPD by suppressing HCK. The combination of LCB and LQ was optimized for anti-inflammation, antioxidation, and anti-fibrosis activities. The iHCK-37 further validated the preventive treatment of LCB and LQ on COPD by inhibiting HCK to exert antioxidant, anti-inflammatory, and anti-fibrotic effects. The combination of LCB and LQ, in a 1:1 ratio, exerted synergistic antioxidative, anti-inflammatory, and anti-fibrotic effects in the treatment of COPD by downregulating HCK. CONCLUSION: The combination of LCB and LQ performed a significant anti-COPD effect via downregulating HCK.

Optimization of Extraction of Four Components from Radix Scrophulariae with Natural Deep Eutectic Solvents and Evaluation of Extract's Antioxidant Activity.

In this research, eight natural deep eutectic solvents (NaDESs) consisting of food-grade ingredients were screened for the extraction of four bioactive compounds (acteoside, cinnamic acid, angoroside C and harpagoside) from radix scrophulariae (RS). Among these NaDESs, Proline-Glycerol NaDES with higher comprehensive score was selected. The Criteria Importance Through Intercriteria Correlation (CRITIC) was applied to calculate the information entropy and the weight of indexes, and figured out a comprehensive score. The weights of acteoside, cinnamic acid, angoroside C and harpagoside were 0.369, 0.172, 0.241 and 0.218, respectively. Response surface methodology (RSM) mathematical model was used to optimize the extraction parameters. The optimal extraction parameters were as follows: extraction time with 42.21 min, NaDES concentration with 52.89%, solid-to-liquid ratio with 1 : 37.05 g/mL and the predicted value of comprehensive score was 0.885. Under the optimal condition, the comprehensive score was 0.903 ± 0.005. Finally, the antioxidant activity experiment revealed that the 1,1-Diphenyl-2-picrylhydrazyl · radical scavenging activity and hydroxyl radical scavenging activity of the extract at 2.0 mg/mL and 1.5 mg/mL were approximately equal to those of ascorbic acid, respectively. The results showed that the extraction condition optimized by RSM combined with CRITIC was reasonable and dependable, and the extract of radix scrophulariae exhibited good antioxidant activity.

Luteolin attenuates CCl4-induced hepatic injury by inhibiting ferroptosis via SLC7A11.

BACKGROUND: Luteolin (3,4,5,7-tetrahydroxy flavone) is reported to strongly protect from acute carbon tetrachloride (CCl4) -induced liver injury or fibrosis. Ferroptosis can be induced by hepatic injury, and contributes to liver fibrosis development. The exact functional mechanism underlying luteolin inhibition of hepatic injury and whether ferroptosis is involved are unclear. METHODS: Mice model and cell model of liver injury were constructed or induced to explore the effect and molecular mechanisms of Luteolin in the treatment of hepatic injury using CCl4. Cell Counting Kit-8 (CCK-8) and flow cytometry were used to evaluate HepG2 cell viability and apoptosis. The differential expressed genes involved in liver injury were scanned using RNA-seq and confirmed using functional study. Western blot was used to detect the indicators related to ferroptosis. RESULTS: Luteolin attenuated hepatic injury by alleviating cell morphology and decreasing serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) levels in vivo mice models, and increasing cell viability, downregulating arachidonate 12-lipoxygenase (ALOX12), cyclooxygenase-2 (COX-2) and P21 protein expression, suppressing apoptosis in vitro cell models. Luteolin also inhibited ferroptosis by stimulating glutathione peroxidase 4 (GPX4) and mitochondrial ferritin (FTMT) protein expression, increasing glutathione (GSH) content, and minimizing Fe2+ and malondialdehyde (MDA) levels. Solute carrier family 7a member 11 (SLC7A11) was identified to be a key regulatory gene that participated in luteolin attenuation of CCl4-induced hepatic injuries in HepG2 cells using Microarray assay. Functional study showed that SLC7A11 can alleviate hepatic injury and ferroptosis. CONCLUSION: Luteolin attenuated CCl4-induced hepatic injury by inhibiting ferroptosis via SLC7A11. SLC7A11 may serve as a novel alternative therapeutic target for hepatic injury.

Artificial neural network optimisation of natural deep eutectic solvent extraction process of Danshen-Gegen and cytotoxicity study.

Natural deep eutectic solvents (NaDESs) are environmentally friendly and efficient for the componential extraction of traditional Chinese medicine compared to conventional organic solvents. In this study, NaDES was screened and employed to extract Danshen-Gegen (DG), and the extraction process was optimised by response surface methodology (RSM) and artificial neural networks (ANN) model. Besides, the in vitro security of extracts of DG were evaluated in PC12 cells. As a result, Betaine-Urea (Bet-Ur) was screened as extraction solvent and ANN model was more accurate than RSM model in optimising the extraction parameter. The extraction process optimised by ANN was as follows: 70% NaDES concentration, 80 mg/mL solid to liquid ratio, 67 °C ultrasonic temperature, and 33 min of ultrasonic time. The comprehensive value of extraction yield was 0.7251 ± 0.84%. IC50 of Bet-Ur, NaDES DG extract and aqueous DG extract were 0.15%, 0.3% and 10% (v/v).