Fritillariae Cirrhosae Bulbus is the dried bulb of perennial herbaceous plants in the Fritillaria genus(Liliaceae family) and is a representative traditional Chinese medicinal material with distinctive regional characteristics. Clinically, it is widely used in the treatment of dry cough, bronchial asthma, and other respiratory diseases, possessing significant medicinal and economic value and being highly esteemed in TCM. Currently, Fritillariae Cirrhosae Bulbus primarily relies on wild harvesting. However, due to excessive collection, its wild resources have drastically declined, and all source species have been classified as category Ⅱ in the List of National Key Protected Wild Plants, exacerbating the supply-demand imbalance in the market. To mitigate this issue, large-scale cultivation through the domestication of wild Fritillariae Cirrhosae Bulbus has become an inevitable trend. However, its strict environmental requirements, low propagation efficiency, high seedling mortality, and immature cultivation techniques have severely hindered industrialization. This study investigates the domestication process of Fritillariae Cirrhosae Bulbus, focusing on seed propagation, seedling cultivation, and medicinal material production. It also reviews the species and distribution of wild resources, their endangered status, market supply-demand dynamics, and the historical and current development of domestication. The findings indicate that enhancing propagation efficiency, optimizing cultivation models, and distinguishing between seed propagation and medicinal material production are key measures to accelerate the industrialization of domesticated Fritillariae Cirrhosae Bulbus. This research aims to promote the industrialization of Fritillariae Cirrhosae Bulbus domestication and provide a reference model for the conservation and sustainable utilization of rare and endangered medicinal plant resources.
Fritillaria/chemistry* ; Endangered Species ; Plants, Medicinal/growth & development* ; Drugs, Chinese Herbal/economics* ; China

Immobilized enzyme-based enzyme electrode biosensors, characterized by high sensitivity and efficiency, strong specificity, and compact size, demonstrate broad application prospects in life science research, disease diagnosis and monitoring, etc. Immobilization of enzyme is a critical step in determining the performance (stability, sensitivity, and reproducibility) of the biosensors. Random immobilization (physical adsorption, covalent cross-linking, etc.) can easily bring about problems, such as decreased enzyme activity and relatively unstable immobilization. Whereas, directional immobilization utilizing amino acid residue mutation, affinity peptide fusion, or nucleotide-specific binding to restrict the orientation of the enzymes provides new possibilities to solve the problems caused by random immobilization. In this paper, the principles, advantages and disadvantages and the application progress of enzyme electrode biosensors of different directional immobilization strategies for enzyme molecular sensing elements by specific amino acids (lysine, histidine, cysteine, unnatural amino acid) with functional groups introduced based on site-specific mutation, affinity peptides (gold binding peptides, carbon binding peptides, carbohydrate binding domains) fused through genetic engineering, and specific binding between nucleotides and target enzymes (proteins) were reviewed, and the application fields, advantages and limitations of various immobilized enzyme interface characterization techniques were discussed, hoping to provide theoretical and technical guidance for the creation of high-performance enzyme sensing elements and the manufacture of enzyme electrode sensors.

Combined seawater Hf and Nd isotope compositions have been applied as reliable tracers of water mass mixing and weathering input changes.The establishment of standardized synchronous extraction methods for Fe-Mn oxyhydroxide in sediments,which serve as effective carriers for isotopic signals of ancient seawater,is a prerequisite and key for paleoceanography research.The research material of this study was the surface sediments of the Western Arctic Ocean obtained from China's 7th Arctic Scientific Expedition,and a reliable simultaneous Nd-Hf isotope extraction method in Fe-Mn oxyhydroxide fraction was established through systematic optimization of pretreatment procedures and key extraction parameters.This research focused on analyzing the effects of pretreatment(Milli-Q water pre-wash)and key extraction parameters(leaching time,solution/solid ratios,concentration of EDTA-2Na,and concentration of mixed solution of hydroxyamine hydrochloride(HH)and acetic acid(HAc))on element extraction efficiency and isotopic composition.The experimental results indicated that the Milli-Q water pre-wash was not necessary,Fe-Mn oxyhydroxide extraction could be directly performed.Nd extraction amount in Fe-Mn oxyhydroxide fraction was not sensitive to changes in extraction conditions,while the Hf extraction amount was significantly affected by leaching time,solution/solid ratios and concentration of EDTA-2Na.The optimal conditions for synchronously extracting Nd-Hf isotopes were as follows:adding 20 mL of a mixed solution of 0.005 mol/L HH+1.5%HAc+0.03 mol/L EDTA-2Na per gram of sample,and reaction at room temperature for 3 h under shaking.Through systematic verification of 87Sr/86Sr ratio,εNd value,εHf value,Al/Nd ratio and Al/Hf ratio,it was confirmed that this method could effectively avoid interferences from residual components and accurately obtain Nd-Hf isotope signals of ancient seawater preserved in sediments.The standardized method established in this work provided reliable technical support for reconstructing water mass mixing between the Arctic,North Atlantic,and North Pacific Oceans and riverine input histories.It also provided important reference for the extraction methods of Nd and Hf isotopes from marine sources in sediments from other sea areas around the world.

Additive manufacturing(3D printing)technology aligns with the direction of precision and customization in future medicine,presenting a significant opportunity for innovative development in high-end medical devices.Currently,research and industrialization of 3D printed medical devices mainly focus on nondegradable implants and degradable implants.Primary areas including metallic orthopaedic implants,polyether-ether-ketone(PEEK)bone implants,and biodegradable implants have been developed for clinical and industrial application.Recent research achievements in these areas are reviewed,with a discussion on the additive manufacturing technologies and applications for customized implants.Challenges faced by different types of implants are analyzed from technological,application,and regulatory perspectives.Furthermore,prospects and suggestions for future development are outlined.

AIM:To investigate the mechanism by which wogonin(WOG)induces ferroptosis in collagen-in-duced arthritis rat fibroblast-like synoviocytes(rat CIA-FLS cells)through the nuclear factor E2-related factor 2(NRF2)/heme oxygenase-1(HO-1)signaling pathway.METHODS:Rat CIA-FLS cells were divided into:control group,low,medium,and high dose of(25,50 and 100 μmol/L)WOG group,ferroptosis inhibitor(LIP-1)group,LIP-1+high dose WOG group,HO-1 agonist cobalt protoporphyrin(COPP)group,and COPP+high dose WOG group.CCK-8 assay was used for cell viability.Crystal violet staining was used for for cell morphology.The levels of oxidative stress markers gluta-thione(GSH),malondialdehyde(MDA),and superoxide dismutase(SOD)were measured.DCFH-DA fluorescent probe was used to detect the intracellular reactive oxygen species(ROS)content as well as Western blot to detect the protein ex-pression levels of Kelch-like ECH-associated protein 1(KEAP-1),NRF2 and HO-1.RESULTS:Compared with the nor-mal control group,administration of WOG treatment resulted in a significant decrease in CIA-FLS cell viability(P<0.01),a significant increase in the level of oxidative stress(P<0.01),a significant increase in the content of ROS(P<0.01),a significant decrease in the level of expression of NRF2 and HO-1 proteins(P<0.01),and a significant increase in the level of KEAP-1(P<0.01)in the rat.Compared with the WOG group,the LIP-1-treated group showed a significant increase in cell viability(P<0.01),a significant decrease in the level of oxidative stress(P<0.01),and a significant de-crease in the content of ROS(P<0.01).Compared with the WOG group,the addition of COPP resulted in a significant in-crease in the protein expression levels of NRF2 and HO-1(P<0.01)and a significant decrease in KEAP-1 levels(P<0.01).CONCLUSION:WOG can induce ferroptosis in rat CIA-FLS cells by promoting oxidative stress through the NRF2/HO-1 signaling pathway.

Hydrogen sulfide,as a third gas signal molecule and neurotransmitter,can play a neuroprotective role by anti-oxidative stress,anti-inflammatory response,metabolic inhibition and other mechanisms.It is of great significance for the occurrence and development of neurodegenerative diseases including Alzheimer's disease(AD)and Parkinson's disease(PD)mediated by neuroinflammation.This article reviews the research progress of hydrogen sulfide and neuroinflammation and its mediated neurodegenerative diseases,so as to provide new ideas for the treatment of neurodegenerative diseases.

Humans ; Stroke, Lacunar ; Mendelian Randomization Analysis ; Leukocytes ; Telomere/genetics* ; Genome-Wide Association Study ; Polymorphism, Single Nucleotide

Objective:To investigate the correlation between food-specific IgG (sIgG) antibodies and phenotypes of chronic spontaneous urticaria (CSU) .Methods:Serum samples were collected from outpatients with active CSU, symptomatic dermographism (SD) , or acute urticaria (AU) , and healthy controls from 5 third-grade class-A hospitals such as the First Hospital of China Medical University between April 2014 and March 2015. Enzyme-linked immunosorbent assay was conducted to detect serum levels of 90 food-sIgG antibodies and total IgE, Western blot analysis to detect levels of 20 allergen-specific IgE antibodies, and chemiluminescent microparticle immunoassay to detect levels of anti-thyroid peroxidase IgG antibodies and anti-thyroglobulin IgG antibodies. Comparisons of normally distributed quantitative data between two groups and among several groups were performed by t test and one-way analysis of variance, respectively; comparisons of non-normally distributed quantitative data between two groups were performed by Mann-Whitney U test; for comparisons of proportions, chi-square test and Fisher′s exact test were used. Results:A total of 248 patients with CSU, 22 with SD, 15 with AU and 13 healthy controls were recruited. The cut-off level for sIgG positivity was 100 U/ml (at least 2+) , and the positive rate of food-sIgG antibodies was slightly higher in the patients with CSU (176/248, 70.97%) , SD (15/22, 68.18%) and AU (11/15) than in the healthy controls (7/13; χ2 = 1.80, P = 0.615) . Among the 248 CSU patients, the proportion of patients with family history of allergic diseases was significantly higher in the sIgG-positive group (71/176, 40.34%) than in the sIgG-negative group (19/72, 26.39%; χ2 = 4.30, P = 0.042) , while no significant difference was observed in the 1-day urticaria activity score (UASday) between the two groups ( Z = 0.18, P = 0.859) . Totally, 177 CSU patients completed 12- to 40-week treatment; their condition could be completely controlled by second-generation H1-antihistamines, and there was no significant difference in the required dosage of second-generation H1-antihistamines between the sIgG-positive group (128 cases) and sIgG-negative group (49 cases; Z = -1.06, P = 0.298) . Conclusions:The prevalence of family history of allergic diseases was relatively high in food-sIgG-positive patients with CSU. However, food-sIgG could not be used as an indicator to reflect the disease activity of CSU and treatment response.

Objective: To explore a simple and feasible method for the isolation and purification of hepatocytes, hepatic stellate cells (HSC), and lymphocytes from mice. Methods: The cell suspension was obtained from male C57bl/6 mice by hepatic perfusion through the portal vein digestion method and then isolated and purified by discontinuous Percoll gradient centrifugation. Trypan blue exclusion was used to determine cell viability. Glycogen staining, cytokeratin 18, and transmission electron microscopy were used to identify hepatic cells. Immunofluorescence was used to detect α-smooth muscle actin combined with desmin in HSCs. Flow cytometry was used to analyze lymphocyte subsets in the liver. Results: After isolation and purification, about 2.7×10(7) hepatocytes, 5.7×10(5) HSCS, and 4.6×106 hepatic mononuclear cells were obtained from the liver of mice with a body weight of about 22g. The cell survival rate in each group was > 95%. Hepatocytes were apparent in glycogen deposited purple-red granules and cytokeratin 18. Electron microscopy showed that there were abundant organelles in hepatocytes and tight junctions between cells. HSC had expressed α-smooth muscle actin and desmin. Flow cytometry showed hepatic mononuclear cells, including lymphocyte subsets such as CD4, CD8, NKs, and NKTs. Conclusion: The hepatic perfusion through the portal vein digestion method can isolate multiple primary cells from the liver of mice at once and has the features of simplicity and efficiency.
Male ; Mice ; Animals ; Keratin-18 ; Actins ; Desmin ; Liver ; Hepatocytes ; Hepatic Stellate Cells

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ²=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent ; Brain Abscess ; Child ; Child, Preschool ; Escherichia coli ; Female ; Humans ; Hydrocephalus ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial/epidemiology* ; Retrospective Studies ; Streptococcus agalactiae ; Streptococcus pneumoniae ; Subdural Effusion ; beta-Lactamases