Preparation and efficacy verification of three-dimensional printed partitioned multi-effect precision-care gel facial mask.

OBJECTIVE: A partition multi-effect precision-care gel facial mask conforming to facial skin characteristics was prepared using three-dimensional (3D) printing technology. METHODS: First, the hydrogel matrix and humectant of a 3D-printed gel for facial masks were screened, and three 3D-printed gels of arbutin, hexapeptide, and salicylic acid were prepared with whitening, wrinkle removal, and oil control functions, respectively. Skin irritation tests were performed on the gels. Physicochemical properties such as pH, heat and cold tolerance were evaluated. The efficacy of three 3D-printed gels was assessed by measuring melanin value, wrinkle depression score, and oil secretion. Finally, the facial mask model design and printing parameters were studied, and a partition multi-effect precision-care gel facial mask was printed in line with facial skin characteristics. RESULTS: For the 3D-printed facial mask, the gel prescription with 2% hydroxyethyl cellulose gel as matrix and 7% glycerol as humectant was the best. The prepared 3D-printed gel did not irritate the human skin, and its physicochemical properties met the Chinese facial mask industry standard (QB/T2872-2017). We showed that three types of 3D-printed gels containing arbutin, hexapeptide, and salicylic acid could be applied to the corresponding parts of the face to solve different problems, such as facial skin dullness, wrinkles, and oil secretion. Therefore, according to facial physiological characteristics, the facial mask model was designed for the forehead and nasolabial fold, which needs to be anti-wrinkled; the cheek, which needs to be whitened; and the nose and chin, which need oil control. The optimal printing parameters were 0.26 mm nozzle diameter, 90 mm/s printing speed, 30% filling density, 140% wire extrusion ratio, and 0.25 mm layer height. Different skin care effects can be achieved using a three-nozzle printer to print arbutin, hexapeptide, or salicylic acid gel on the mask's forehead and nasolabial fold, cheek, and nose and chin, respectively. CONCLUSION: The 3D-printed partition multi-effect care gel facial mask prepared according to the skin features of different parts of the face can overcome the problem of the single skincare effect of the mass-produced facial masks.

OBJECTIF: Un masque facial de soin de précision en gel à effets multiples, adapté aux caractéristiques de la peau du visage, a été préparé à l'aide de la technologie d'impression tridimensionnelle (3D). MÉTHODES: Tout d'abord, la matrice d'hydrogel et l'humectant d'un gel imprimé en 3D pour les masques faciaux ont été sélectionnés, et trois gels imprimés en 3D d'arbutine, d'hexapeptide et d'acide salicylique ont été préparés avec des fonctions de blanchiment, d'élimination des rides et de contrôle du sébum, respectivement. Des tests d'irritation cutanée ont été réalisés sur les gels. Les propriétés physicochimiques telles que le pH et la tolérance à la chaleur et au froid ont été évaluées. L'efficacité des trois gels imprimés en 3D a été évaluée en mesurant la valeur de la mélanine, le score de dépression des rides et la sécrétion de sébum. Enfin, la conception du modèle de masque facial et les paramètres d'impression ont été étudiés, et un masque facial de gel de soin de précision à effets multiples a été imprimé en fonction des caractéristiques de la peau du visage. RÉSULTATS: Pour le masque facial imprimé en 3D, la prescription de gel avec 2 % de gel d'hydroxyéthylcellulose comme matrice et 7 % de glycérol comme humectant était la meilleure. Le gel imprimé en 3D n'a pas irrité la peau humaine et ses propriétés physicochimiques sont conformes à la norme industrielle chinoise relative aux masques faciaux (QB/T2872­2017). Nous avons montré que trois types de gels imprimés en 3D contenant de l'arbutine, de l'hexapeptide et de l'acide salicylique pouvaient être appliqués aux parties correspondantes du visage pour résoudre différents problèmes, tels que l'aspect terne de la peau du visage, les rides et la sécrétion de sébum. Par conséquent, en fonction des caractéristiques physiologiques du visage, le modèle de masque facial a été conçu pour le front et le sillon nasogénien, qui doivent être antirides, la joue, qui doit être blanchie, et le nez et le menton, qui ont besoin d'un contrôle du sébum. Les paramètres d'impression optimaux étaient les suivants : diamètre de buse de 0,26 mm, vitesse d'impression de 90 mm/s, densité de remplissage de 30 %, rapport d'extrusion du fil de 140 % et hauteur de couche de 0,25 mm. Différents effets de soin de la peau peuvent être obtenus en utilisant une imprimante à trois buses pour imprimer de l'arbutine, de l'hexapeptide ou du gel d'acide salicylique sur le front et le sillon nasogénien, la joue, le nez et le menton du masque, respectivement. CONCLUSION: Le masque facial en gel de soin à effets multiples imprimé en 3D et préparé en fonction des caractéristiques de la peau des différentes parties du visage peut résoudre le problème de l'effet de soin unique des masques faciaux produits en masse.

NAD+ metabolism and eye diseases: current status and future directions.

Currently, there are no truly effective treatments for a variety of eye diseases, such as glaucoma, age-related macular degeneration (AMD), and inherited retinal degenerations (IRDs). These conditions have a significant impact on patients' quality of life and can be a burden on society. However, these diseases share a common pathological process of NAD+ metabolism disorders. They are either associated with genetically induced primary NAD+ synthase deficiency, decreased NAD+ levels due to aging, or enhanced NAD+ consuming enzyme activity during disease pathology. In this discussion, we explore the role of NAD+ metabolic disorders in the development of associated ocular diseases and the potential advantages and disadvantages of various methods to increase NAD+ levels. It is essential to carefully evaluate the possible adverse effects of these methods and conduct a more comprehensive and objective assessment of their function before considering their use.

Chrysomycin A Regulates Proliferation and Apoptosis of Neuroglioma Cells via the Akt/GSK-3ß Signaling Pathway In Vivo and In Vitro.

Glioblastoma (GBM) is a major type of primary brain tumor without ideal prognosis and it is therefore necessary to develop a novel compound possessing therapeutic effects. Chrysomycin A (Chr-A) has been reported to inhibit the proliferation, migration and invasion of U251 and U87-MG cells through the Akt/GSK-3ß signaling pathway, but the mechanism of Chr-A against glioblastoma in vivo and whether Chr-A modulates the apoptosis of neuroglioma cells is unclear. The present study aims to elucidate the potential of Chr-A against glioblastoma in vivo and how Chr-A modulates the apoptosis of neuroglioma cells. Briefly, the anti-glioblastoma activity was assessed in human glioma U87 xenografted hairless mice. Chr-A-related targets were identified via RNA-sequencing. Apoptotic ratio and caspase 3/7 activity of U251 and U87-MG cells were assayed via flow cytometry. Apoptosis-related proteins and possible molecular mechanisms were validated via Western blotting. The results showed that Chr-A treatment significantly inhibits glioblastoma progression in xenografted hairless mice, and enrichment analysis suggested that apoptosis, PI3K-Akt and Wnt signaling pathways were involved in the possible mechanisms. Chr-A increased the apoptotic ratio and the activity of caspase 3/7 in U251 and U87-MG cells. Western blotting revealed that Chr-A disturbed the balance between Bax and Bcl-2, activating a caspase cascade reaction and downregulating the expression of p-Akt and p-GSK-3ß, suggesting that Chr-A may contribute to glioblastoma regression modulating in the Akt/GSK-3ß signaling pathway to promote apoptosis of neuroglioma cells in vivo and in vitro. Therefore, Chr-A may hold therapeutic promise for glioblastoma.

Bitter Almond Albumin ACE-Inhibitory Peptides: Purification, Screening, and Characterization In Silico, Action Mechanisms, Antihypertensive Effect In Vivo, and Stability.

Almond expeller is an undeveloped reservoir of bioactive peptides. In the current study, a zinc ion ligand Arg-Pro-Pro-Ser-Glu-Asp-Glu-Asp-Gln-Glu (RPPSEDEDQE) offering a noncompetitive inhibitory effect on ACE (IC50: 205.50 µmol·L-1) was identified from almond albumin hydrolysates via papain and thermolysin hydrolysis, subsequent chromatographic separation, and UPLC-Q-TOF-MS/MS analysis. Molecular docking simulated the binding modes of RPPSEDEDQE to ACE and showed the formation of hydrogen bonds between RPPSEDEDQE and seven active residues of ACE. Moreover, RPPSEDEDQE could bind to fifteen active sites of ACE by hydrophobic interactions, and link with the His387 and zinc ions of the zinc tetrahedral coordination. Ultraviolet wavelength scanning and Fourier-transformed infrared spectroscopy analysis revealed that RPPSEDEDQE can provide multiple binding sites for zinc ions. However, RPPSEDEDQE cannot bind with any central pocket of ACE, which was evidenced by an inhibition kinetics experiment. Additionally, the zinc-chelating capacity and inhibiting ability against ACE of RPPSEDEDQE were both not significantly reduced by the hydrolysis of gastrointestinal enzymes. A moderate to high dose of RPPSEDEDQE (100-150 mg·kg bw-1) significantly reduced the systolic and diastolic blood pressure of spontaneous hypertensive rats, but chelation with zinc ions decreased its antihypertensive efficiency. These results indicate that bitter almond albumin peptides may be used for lowering blood pressure.

A TTP-incorporated scoring model for predicting mortality of solid tumor patients with bloodstream infection caused by Escherichia coli.

BACKGROUND: Few mortality-scoring models are available for solid tumor patients who are predisposed to develop Escherichia coli-caused bloodstream infection (ECBSI). We aimed to develop a mortality-scoring model by using information from blood culture time to positivity (TTP) and other clinical variables. METHODS: A cohort of solid tumor patients who were admitted to hospital with ECBSI and received empirical antimicrobial therapy was enrolled. Survivors and non-survivors were compared to identify the risk factors of in-hospital mortality. Univariable and multivariable regression analyses were adopted to identify the mortality-associated predictors. Risk scores were assigned by weighting the regression coefficients with corresponding natural logarithm of the odds ratio for each predictor. RESULTS: Solid tumor patients with ECBSI were distributed in the development and validation groups, respectively. Six mortality-associated predictors were identified and included in the scoring model: acute respiratory distress (ARDS), TTP ≤ 8 h, inappropriate antibiotic therapy, blood transfusion, fever ≥ 39 °C, and metastasis. Prognostic scores were categorized into three groups that predicted mortality: low risk (< 10% mortality, 0-1 points), medium risk (10-20% mortality, 2 points), and high risk (> 20% mortality, ≥ 3 points). The TTP-incorporated scoring model showed excellent discrimination and calibration for both groups, with AUC being 0.833 vs 0.844, respectively, and no significant difference in the Hosmer-Lemeshow test (6.709, P = 0.48) and the chi-square test (6.993, P = 0.46). Youden index showed the best cutoff value of ≥ 3 with 76.11% sensitivity and 79.29% specificity. TTP-incorporated scoring model had higher AUC than no TTP-incorporated model (0.837 vs 0.817, P < 0.01). CONCLUSIONS: Our TTP-incorporated scoring model was associated with improving capability in predicting ECBSI-related mortality. It can be a practical tool for clinicians to identify and manage bacteremic solid tumor patients with high risk of mortality.

A Novel Preparation Method for Effervescent Tablets of Xianganfang Containing Fresh Juice using a Semi-Solid Extrusion 3D Printer with Three Cartridge Holders.

This study aimed to prepare effervescent tablets of traditional Chinese medicine Xianganfang with fresh juice using a semi-solid 3D printer with three cartridge holders to seperate acid and alkali source by drug paste through model design to avoid sticking impact and premature effervescence during the tableting in the conventional preparation process. The powder of Xianganfang including fresh juice of Phyllanthus emblica and licorice extract was obtained by vacuum freeze-drying with 50% mannitol as cryoprotectant. Then, the formulation of 3D-printed effervescent tablets was investigated. Further 5% HPMC hydroalcoholic gel was mixed with sodium bicarbonate and freeze-dried Xianganfang powder to prepare alkali source and drug paste respectively while 30% PVP ethanol solution was mixed with tartaric acid to prepare acid source paste; these three pastes had good printability. The pastes of drug, acid, and alkali were loaded into three syringe cartridges separately and numbered as "3," "5," and "7," according to cartridge holders of the 3D printer, and printed in the order of "537,353,735" for separating acid and alkali by drug to avoid premature effervescence. And the basic printing parameters were optimized. The tablets were evaluated by the appearance, tablet weight variation, hardness, disintegration time, friability, pH, and stability. The physicochemical properties all conformed to the Chinese Pharmacopoeia 2020 edition. The content of the active ingredient gallic acid was 0.769 ± 0.019 mg/g. This study provided a new method to prepare effervescent tablets of traditional Chinese medicine with fresh juice using 3D printing technology.

Career choice and influential factors among medical students majoring in psychiatry in China.

BACKGROUND: The undergraduate program of psychiatry has been widely established in recent years to improve the education and recruitment of psychiatrists in China. We aim to investigate the career choice of medical students majoring in psychiatry in China and the influential factors. METHOD: This multicenter study was conducted in 26 medical schools in China from May to October of 2019. Participants included 4610 medical students majoring in psychiatry and 3857 medical students majoring in clinical medicine. Multivariable logistic regression was used to investigate the influential factors of students' choices of psychiatry at matriculation and as a career. RESULTS: 44.08% of psychiatry majored students gave psychiatry as a first choice at matriculation, and 56.67% of them would choose psychiatry as a career, which was in sharp contrast to the proportion of clinical medicine majored students who would choose psychiatry as a career (0.69%). Personal interest (59.61%), suggestions from family members (27.96%), and experiencing mental problems (23.19%) were main reasons for choosing psychiatry major at matriculation. Personal interest (odds ratio [OR] = 2.12, 95% confidence interval [CI] = 1.87-2.40), experiencing a psychiatry clerkship (OR = 1.99, 95% CI = 1.28-3.08), being female (OR = 1.50, 95% CI = 1.30-1.68), experiencing mental problems (OR = 1.33, 95% CI = 1.28-1.56), and suggestions from family members (OR = 1.25, 95% CI = 1.08-1.46) correlated positively with students' choice of psychiatry as career. Students who lacked psychiatry knowledge (OR = 0.49, 95% CI = 0.29-0.85) or chose psychiatry because of lower admission scores (OR = 0.80, 95% CI = 0.63-0.97) were less likely to choose psychiatry as a career. CONCLUSION: More than half of psychiatry majored medical school students planned to choose psychiatry as their career, whereas very few students in the clinic medicine major would make this choice. Increasing students' interest in psychiatry, strengthening psychiatry clerkships, and popularizing psychiatric knowledge are modifiable factors to increase the psychiatry career intention. The extent to which medical students' attitudes toward psychiatry can be changed through medical school education and greater exposure to psychiatry will need further investigation.

Warpage optimization and influence factors analysis of 3D printing personalized JJY tablets.

To explore the feasibility of preparing traditional Chinese medicine using 3 D printing technology and reduce warpage commonly occurs in large-size tablets, we investigated the prescription, warpage optimization and influence factors of 3 D printing Jiuxiang Jianpi Yangwei (JJY) tablets. The procedures used conformed to the requirements of the 2015 edition of the Chinese Pharmacopeia. The results of the prescription screening showed that 75% ethanol and HPMC (9%) could be adhesives. Meanwhile, stevia (0.5%) and citric acid (0.5%) improved the taste of the 3 D printed JJY tablets. To ensure the quality and appearance of the printed tablets, the best parameters were as follows: drying at room temperature, 40% of the filling density, a 3 mm model height, two outer ring numbers and a printing speed of 15 mm/s. The optimized printed tablets had a smooth appearance, suitable hardness, with the weight uniformity in accordance with the Pharmacopeia. We also prepared personalized JJY cartoon tablets (which contained images of a big-headed pig and a small yellow duck) which were designed to increase the compliance of children when taking their medications. In conclusion, this study reported that 3 D printing technology has great potential for preparing traditional Chinese medicines, and it provided guidance for 3 D printing tablets without warpage.

Optimized preparation of vinpocetine micelles and in vivo evaluation of its pharmacokinetics in rats.

This study aimed to develop a novel monomethoxy poly(ethylene glycol)-b-poly(D, L-lactide) (mPEG5000-PLA10 000) micelle drug delivery system to improve vinpocetine's (VP) dissolution and sustain VP concentrations in plasma. Three micelle fabrication methods were examined to maximize VP loading, followed by structurally characterization and investigation in vitro release and in vivo pharmacokinetics in Sprague-Dawley rats. The thin-film hydration is the most appropriate method of the three methods because of its high loading content. The loaded micelles exhibited a sustained release behavior up to 48 h. Following intraperitoneal administration (9 mg/kg), VP loaded micelles provided significantly higher (335%) AUC (area under concentration-time) compared to VP injection. And also increased the mean residence time [MRT(0-t)] and elimination half-life (t1/2z). There were obviously two peaks at 2 h and 9 h in VP loaded micelles concentration-time profile. In summary, these data demonstrated that poly mPEG-PLA micelles can efficiently sustain VP concentrations in plasma for 36 h, thus apprehending polymeric micelles suitability as poor aqueous solubility drug carriers.

Knockdown of the lncRNA SNHG8 inhibits cell growth in Epstein-Barr virus-associated gastric carcinoma.

BACKGROUND: Epstein-Barr virus (EBV) infection is causatively associated with a variety of human cancers, including gastric cancer (GC), which has one of the highest mortality rates of all human cancers. Long non-coding RNAs (lncRNAs) show important regulatory roles in human GC. SNHG8 is a recently identified lncRNA that was reported to show abnormal expression pattern in GC. However, little is known of its biological function in EBV-associated GC. METHODS: We used cell viability, colony formation and cell cycle assays to investigate the roles of lncRNA SNHG8 in the cell growth of EBV-associated GC. RESULTS: The transcript levels of SNHG8 in the cultured EBV-associated GC cells were significantly higher in the cultured EBV-associated GC cells compared with the levels in normal human gastric mucosal cells and EBV-negative GC cells. Knockdown of SNHG8 with specific shRNAs inhibited cell proliferation and colony formation and arrested the cell cycle in the G0/G1 phase in vitro. We also found that knockdown of SNHG8 suppressed tumor growth in vivo. CONCLUSIONS: These data indicate the pro-oncogenic potential of SNHG8 in EBV-associated GC, meaning it is a latent therapeutic target for the treatment of this type of cancer.

Novel Flavones from the Root of Phytolacca acinosa Roxb.

Two new flavones, 6,7-methylenedioxy-4-hydroxypeltogynan-7'-one (1), cochliophilin B (2), as well as two known ones, cochliophilin A (3) and 6-methoxy-7-hydroxy flavone (4), were isolated from the ethanol extract of the root of Phytolacca acinosa Roxb. Compound 1 is a flavanol framework with one δ-lactone unit, which is rather rare in nature. The structures of the new compounds were determined on the basis of extensive spectroscopic (IR, MS, 1D- and 2D-NMR) analyses, the absolute configuration of 1 was established by comparing experimental and calculated electronic circular dichroism spectra. The structures of known compounds were fixed by comparison with literatures data. Compounds 2 and 4 showed modest inhibitory activities against BEL-7402 cell line, with IC50 values of 28.22 and 39.16 µmol/L, respectively.

Sohlh2 inhibits human ovarian cancer cell invasion and metastasis by transcriptional inactivation of MMP9.

Identifying key mediators of cancer invasion and metastasis is crucial to the development of new and more effective therapies. We previously identified Sohlh2 as an important inhibitor of ovarian cancer cell proliferation. However, the function of Sohlh2 in cell migration and invasion remains unknown. In this paper, we report a novel Sohlh2 to MMP9 signaling pathway in the invasive ovarian cancer. Using immunohistochemistry staining, we revealed Sohlh2 expression was inversely correlated with the invasive human ovarian cancers. In vitro experiments, forced expression of Sohlh2 led to a significant reduction in cancer cell migration and invasion. Conversely, silencing of Sohlh2 enhanced ovarian cancer cell migration and invasion. Experiments using nude mice demonstrated that the ectopic Sohlh2 expression inhibited the HO8910 cell capability of the metastasis to the lungs and livers. Ectopic overexpression of Sohlh2 in the invasive HO8910 cells reduced the MMP9 expression, whereas Sohlh2 knockdown from the non-invasive, SKOV3 cells increased the MMP9 expression. Promoter activation and binding analyses indicated that Sohlh2 repressed the MMP9 expression by directly acting on the MMP9 gene promoter. Inhibition of MMP9 dramatically blocked the Sohlh2 knockdown-enhanced SKOV3 cell invasion, and ectopic expression of MMP9 compensated for the anti-invasive activity of Sohlh2 in HO8910 cells. Overall, these results demonstrate for the first time that Sohlh2 functions as a tumor metastasis suppressor. Modulation of Sohlh2 expression has the potential to be a target for cancer therapy. © 2015 Wiley Periodicals, Inc.

Clinical prognostic factors for time to positivity in cancer patients with bloodstream infections.

PURPOSE: Time to positivity (TTP) has been used in recent years as a simple and rapid method for the additional characterization of the degree of bacteremia. However, prognostic factors for TTP in cancer patients with bloodstream infections have rarely been studied. The aim of this study was to investigate the clinical factors for TTP involving various isolated organisms in cancer patients. METHODS: We analyzed 386 episodes of bloodstream infections (BSIs) in patients with or without cancer during a 19 month period. Information on age, gender, tumor type, ICU stay, organisms, multidrug resistance (MDR), TTP and outcome was collected. Multivariate logistic regression analysis was performed. RESULTS: The mean TTP of Enterobacteriaceae in patients with hepatocellular carcinoma, gastroenterological cancer, and lung cancer was shorter than in non-cancer patients (9.86 ± 3.22, 10.05 ± 3.47, 8.85 ± 2.78 vs 13.11 ± 5.37 h). The mean TTP of nonfermentative bacilli in patients with lung cancer (12.37 ± 5.96 h) and hematologic diseases (8.72 ± 4.21 h) was also shorter than in non-cancer patients (20.74 ± 2.46 h), and the mean TTP of Staphylococcus isolates was significantly different between non-cancer patients (22.06 ± 3.71 h) and hematologic disease patients (11.93 ± 5.44 h). The presence of a benign tumor was a significant prognostic factor for a long TTP only in the Staphylococci group (OR 0.076, 95 % CI 0.014-0.412), according to multivariate analysis. MDR (OR 2.178, 95 % CI 1.196-4.239) was an independent significant predictor in the Enterobacteriaceae group, with a short TTP, and it was also a significant clinical factor for a long TTP in nonfermentative bacilli and the Staphylococci group (OR 5.037, 95 % CI 1.065-23.82; OR 0.167, 95 % CI 0.059-0.474). CONCLUSION: Time to positivity provides useful diagnostic and prognostic information for the differentiation of frequently isolated organisms. This information may help clinicians to use the correct antibiotics in a timely manner to treat cancer patients with BSIs based on clinical factor analysis.

Molecular surveillance of candidemia due to Candida albicans among cancer patients during 2009 to 2013 by microsatellite typing.

BACKGROUND: Since the high morbidity and mortality of candidemia among cancer patients, the epidemiology has been underlined. In recent years, Candida species genotyping has been established, which could provide detail characteristics of epidemiology and has been underscored for candidemia preventing strategies. METHODS: Data of cancer patients with candidemia and hospitalized in Tianjin Medical University Cancer Institute and Hospital (TMUCIH) during 2009-2013 were reviewed. Species identification was carried out by using VITEK-2 Compact. Microsatellite typing was performed for molecular analysis. SPSS 20.0 and MVSP 3.22 software were used for statistical and clustering analysis, respectively. RESULTS: Total of 36 isolates of Candida albicans were recovered from 36 cancer patients with nosocomial candidemia in TMUCIH during the period of 2009-2013 included in the study. Total of 17 genotypes were identified and 2 of them were endemic genotypes, which caused 21 (58.3%) of 36 episodes of candidemia. Hepatobiliary oncology, ICU and gastrointestinal oncology were the main wards of infections due to endemic strains. Gastrointestinal cancer and insertion of a nasogastric tube were the predictors of infections caused by endemic strains (p = 0.014 and p = 0.041, respectively). For the 36 cases, crude mortality was up to 30.6%, and there was no significant difference between infections due to endemic and non-endemic strains (p = 0.077). CONCLUSIONS: This study proved that endemic stains of C. albicans could exist for a long period and mainly in a few wards. Patients with gastrointestinal cancer or nasogastric tube insertion were more sensitive to endemic C. albicans.

Synergism of herbicide toxicity by 5-aminolevulinic acid is related to physiological and ultra-structural disorders in crickweed (Malachium aquaticum L.).

Selection of effective herbicides to control weeds has been one of the major objectives of scientists. This study determines the differential tolerance or susceptibility of crickweed (Malachium aquaticum L.) to various concentration combinations of 5-aminolevulinic acid (ALA) (1, 10 and 100mg/L) and propyl 4-(2-(4,6-dimethoxypyrimidin-2-yloxy)benzylamino)benzoate (ZJ0273) (100, 200, and 500mg/L). ALA was applied as pre- and post-treatment alone or in combination with ZJ0273. Results showed that ZJ0273 stress alone imposed negative effects on M. aquaticum seedling's growth, net photosynthetic rates and SPAD values, and the rate of decline was consistently increased with the increase in ZJ0273 concentration. The ZJ0273 treatment showed a gradual decrease in the activities of antioxidant enzymes peroxidase (POD), superoxide dismutase (SOD), and ascorbate peroxidase (APX), and increase in the accumulation of malondialdehyde (MDA). Changes in chloroplast swelling, increased number of plastoglobuli, disruption of thylakoid, disintegrated mitochondria and turbid nucleoplasm were noticed. Moreover, SDS-PAGE analysis of total proteins revealed that herbicide stress in the leaves was associated with the decrease or disappearance of some protein bands. Further, two-dimensional gel electrophoresis (2-DE) results showed that proteins in different spots were classified into three types for M. aquaticum. These results indicate that the combined treatment of ALA and ZJ0273 synergizes the herbicide toxicity which is different from its independent effects on M. aquaticum and thus, could improve weed control efficacy.

High altitude retinopathy: An overview and new insights.

High altitude retinopathy (HAR) is a common ocular disorder that occurs on ascent to high altitude. There are many clinical symptoms, retinal vascular dilatation, retinal edema and hemorrhage are common. These usually do not or slightly affect vision; rarely, severe cases develop serious or permanent vision loss. At present, the research progress of HAR mainly focuses on hemodynamic changes, blood-retinal barrier damage, oxidative stress and inflammatory response. Although the related studies on HAR are limited, it shows that HAR still belongs to hypoxia, and hypobaric hypoxia plays an aggravating role in promoting the development of the disease. Various studies have demonstrated the correlation of HAR with acute mountain sickness (AMS) and high-altitude cerebral edema (HACE), so a deeper understanding of HAR is important. The slow ascent rates and ascent altitude are the key to preventing any altitude sickness. Research on traditional chinese medicine (TCM) and western medicine has been gradually carried out. Further exploration of the pathogenesis and prevention strategies of HAR will provide better guidance for doctors and high-altitude travelers.

Improving grassland ecosystem services for human wellbeing in the karst desertification control area: Anthropogenic factors become more important.

Elucidating the spatial and temporal patterns of grassland ecosystem service value (ESV) changes under different karst geomorphic types (KGTs) is crucial for promoting regional sustainable development and enhancing human well-being. Karst ecosystems are characterized by high spatial heterogeneity. However, analyses of the drivers of spatial and temporal changes in ESV in karst grasslands at multiple scales are lacking. In this study, the South China Karst (SCK) region was selected as the focus area, the gross ecosystem product (GEP) accounting method was used to quantify the grassland ESV from 2000 to 2020, and the GeoDetector model was used to elucidate the spatial and temporal evolution of the GEP, the drivers, and their interactions in different KGTs. The results indicate the following: (1) Over the past 20 years, the grassland GEP of SCK has increased from ¥ 14,844.24 × 108 in 2000 to ¥ 17,174.90 × 108 in 2020. Among the various KGTs, the karst gorge exhibited the fastest GEP increase (24.93 %) and karst hilly depressions the slowest (6.22 %). (2) The karst grassland GEP showed a strong positive spatial correlation with significant clustering characteristics (p < 0.05). (3) There are significant differences in the factors influencing the GEP of grasslands with different KGT values, and although they are generally influenced by factors such as NPP, precipitation, and population density, anthropogenic factors are becoming increasingly important. In addition, the multifactor interaction explained GEP better than the single factor. Based on our findings, we propose targeted grassland ESV restoration approaches and management recommendations for various KGTs dominated by distinct factors. Our results provide a scientific basis for decision-making regarding karst ecosystem service enhancement and value realization.

Comprehensive Quality Evaluation of Danggui-Jianzhong Decoction by Fingerprint Analysis, Multi-Component Quantitation and UPLC-Q-TOF-MS.

Danggui-Jianzhong decoction (DGJZ) is a famous classical traditional Chinese medicine formula, which ingredients are complex and the quality is difficult to control. Our study aimed to identify the overall chemical profile of DGJZ qualitatively by ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and UPLC. A total of 77 components, including terpenoids, flavonoids, phenolic acids, gingerols and other components, were firstly detected and characterized by UPLC-Q-TOF-MS and 18 peaks marked after analyzing the UPLC fingerprint. Finally, paeoniflorin, liquiritin, ferulic acid, cinnamic acid, glycyrrhizic acid and 6-gingerol were quantified, which was validated in terms of linearity, precision, accuracy, repeatability and recovery. Taken together, the chemical constitutes of DGJZ were systematically identified and a reliable quantitative method coupled with fingerprint analysis was successfully employed for evaluating the holistic quality, which will provide a robust foundation for the quality control of DGJZ.

Analysis on dynamic changes of etizolam and its metabolites and exploration of its development prospect using UPLC-Q-exactive-MS.

As one of the most widely abused designer benzodiazepines in the world, etizolam has been found in many cases in many countries. In this study, UPLC-Q-Exactive-MS was used for the first time to establish a dynamic change model of etizolam and its metabolites in rats. Compared with previous studies, the detection sensitivity and reproducibility of the instrument were higher. In the experiment, we optimized the traditional pharmacokinetic model based on Gauss function. According to the significant difference of etizolam in the plasma elimination phase of rats, a new pharmacokinetic model based on Lorentz function was established to describe the dynamic changes of etizolam more rigorously, which made the error effects lower and the accuracy of the pharmacokinetic parameters was improved. At the same time, the pharmacokinetic parameters of etizolam were compared with four other designer benzodiazepines reported in previous studies in rats, and we found the direct reason for the popularity of etizolam in the NPS market and explored the future development of etizolam for the first time. In addition, 21 metabolites were found through rat experiments to effectively detect etizolam abuse for a long time, of which 4 metabolites had the longest detection window and could be used as long-acting metabolites for experiments, which greatly prolongs the detection window and extends the time range in which etizolam was detected in real cases. This study is the first to conduct a systematic and comprehensive study on the metabolism and pharmacokinetics of etizolam and find out the direct reason for the prevalence of etizolam abuse, and we also discuss the development trend of etizolam in the future market of new psychoactive substances, which is beneficial for forensic experts to assess the trend of drug abuse and can provide reference for relevant drug control and drug treatment.

Targeting the PANoptosis signaling pathway for myocardial protection: therapeutic potential of Xian Ling Gu Bao capsule.

Introduction: Myocardial infarction (MI), the most prevalent ischemic heart disease, constitutes a primary cause of global cardiovascular disease with incidence and mortality. The pathogenesis of MI is exceedingly intricate, with PANoptosis playing a pivotal role in its pathological process. Xian Ling Gu Bao capsule (XLGB) contains various active components, including flavonoids, terpenes, and phenylpropanoids, and exhibits a wide range of pharmacological activities. However, it remains unclear whether XLGB can protect the myocardium from damage after MI. This study aimed to investigate the impact of XLGB on isoprenaline (ISO)-induced MI in mice and its potential mechanisms. Methods: This study assessed the protective effects of XLGB against ISO-induced MI through techniques such as echocardiography, HE staining, Masson staining, and enzyme-linked immunosorbent assay (ELISA). Furthermore, the potential mechanisms of XLGB's protective effects on MI were explored using bioinformatics, molecular docking, and molecular dynamics simulations. These mechanisms were further validated through immunofluorescence staining and Western blotting. Results: The results demonstrated that various doses of XLGB exhibited a significant reduction in myocardial injury induced by myocardial infarction. Intriguingly, higher dosages of XLGB displayed superior therapeutic efficacy compared to the positive control metoprolol. This protective effect is primarily achieved through the inhibition of oxidative stress and the inflammatory processes. Furthermore, we have elucidated that XLGB protected the myocardium from MI-induced damage by suppressing PANoptosis, with a critical role played by the NLRP3/Caspase3/RIP1 signaling pathway. Of particular note, the primary compounds of XLGB were found to directly interact with NLRP3/Caspase3/RIP1, a discovery further validated through molecular docking and molecular dynamics simulations. This suggests that NLRP3/Caspase3/RIP1 may be a therapeutic target for XLGB-induced myocardial protection. Conclusion: In summary, our findings reveal a novel property of XLGB: reverses myocardial damage following MI by inhibiting the NLRP3/Caspase3/RIP1-mediated PANoptosis pathway.