Olfactory receptors (ORs) form the largest superfamily of G protein-coupled receptors (GPCRs). Traditionally recognized for their role in the nasal olfactory epithelium, where they mediate the sense of smell, accumulating evidence has firmly established their ectopic expression in non-olfactory tissues, including the intestine, lungs, and kidneys. The intestine, as the primary site for nutrient digestion and absorption, harbors a highly complex chemical environment. To adapt to this environment, the gut employs a sophisticated network of “chemosensors” to monitor luminal contents and maintain homeostasis. Among these sensors, intestinal ORs have emerged as crucial functional components, serving as a molecular bridge that connects environmental chemical signals—such as food-derived odorants—to specific physiological responses. This discovery has significantly deepened our understanding of how dietary flavors and compounds influence intestinal physiology at the molecular level. This review systematically summarizes the expression profiles, ligand classification, and biological functions of ORs within the gastrointestinal tract. Studies indicate that intestinal ORs exhibit distinct spatial distribution patterns across different gut segments and display cell-type specificity, particularly within enterocytes and enteroendocrine cells. These receptors function as versatile sensors capable of recognizing a wide variety of ligands, including exogenous dietary components, gut microbiota metabolites such as short-chain fatty acids, and endogenous small molecules like azelaic acid. Upon activation by specific ligands, intestinal ORs trigger intracellular signaling cascades, primarily involving the AC-cAMP-PKA pathway or calcium influx channels. A major focus of this review is to elucidate the molecular mechanisms by which these receptors regulate the secretion of gut hormones. Activation of specific ORs in enteroendocrine cells has been shown to stimulate the release of hormones such as glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and serotonin (5-HT), thereby modulating systemic energy metabolism, glucose homeostasis, and gastrointestinal motility. Furthermore, the review addresses the critical roles of ORs in immune regulation and pathology. Evidence suggests that specific ORs contribute to the maintenance of intestinal immune homeostasis and may offer protection against inflammation. Beyond their involvement in inflammatory responses, ORs such as Olfr78 have been shown to regulate the differentiation and function of intestinal endocrine cells. Similarly, Olfr544 has been demonstrated to alleviate intestinal inflammation by remodeling the gut microbiome and metabolome. These findings collectively suggest that specific ORs hold promise as therapeutic targets for mitigating intestinal inflammation and maintaining gut homeostasis. Additionally, the review explores the emerging role of ORs in cancer. Although OR expression is often downregulated in tumor tissues compared to normal mucosa, activation of specific ORs by certain ligands can inhibit tumor cell proliferation and migration and induce apoptosis via pathways such as MEK/ERK and p38 MAPK. Conversely, other receptors, such as OR7C1, may serve as biomarkers for cancer-initiating cells. In conclusion, intestinal ORs represent a vital component of the gut’s sensory network. The review also discusses the translational potential of these findings. By elucidating the precise pairing relationships between dietary components and specific ORs, novel therapeutic strategies could be developed. Intestinal ORs may thus emerge as promising targets for nutritional and pharmacological interventions in metabolic diseases, inflammatory bowel diseases, and malignancies.

Metabolic dysfunction-associated fatty liver disease （MAFLD） is currently the most prevalent chronic liver disease worldwide， and its disease spectrum encompasses simple steatosis， metabolic-associated steatohepatitis， hepatic fibrosis， liver cirrhosis， and hepatocellular carcinoma. Recent studies have shown that hepatic macrophages play an important regulatory role in the development and progression of MAFLD. Hepatic macrophages mainly consist of resident Kupffer cells and monocyte-derived macrophages， which participate in the pathophysiological processes of the disease by regulating inflammatory response， lipid metabolism， fibrogenic process， and cell death pathways. This article summarizes the diversity and functional plasticity of hepatic macrophages in MAFLD， reviews their interactions with hepatocytes and gut microbiota， elaborates on the core mechanism of hepatic macrophages and related signaling pathways in the progression of MAFLD， and further discusses novel therapeutic strategies targeting hepatic macrophages. An in-depth understanding of the mechanism of action of hepatic macrophages in MAFLD may provide a crucial theoretical basis for developing precise therapeutic approaches for this disease.

A solid-phase extraction-ultra-performance liquid chromatography-tandem mass spectrometry(SPE-UPLC-MS/MS)method was established for simultaneous determination of 10 kinds of neonicotinoid pesticide residues in aquaculture water.Based on the chemical properties of neonicotinoid pesticides and the matrix characteristics of aquaculture water,suitable temporary storage methods for water samples and appropriate solid-phase extraction columns were selected,and the extraction conditions(including elution solvents and sample loading volumes)were optimized.The method employed acetonitrile and 5 mmol/L ammonium acetate solution(containing 0.1%formic acid)as the mobile phase and an Oasis HLB solid-phase extraction column combined with PSA as a dispersive sorbent for sample purification.The method exhibited good linearity in detection of neonicotinoid in concentration range of 0.2-50 ng/mL(R2>0.99797),with a detection limit of 0.5 ng/L and a quantification limit of 1 ng/L,which were significantly lower than the maximum acceptable method detection limits(9-500 ng/L)for neonicotinoid insecticides in water published by the European Commission.In pond water,rice-fish water,and seawater,the average recoveries of the 10 target analytes were 74.6%-114.1%,with relative standard deviations ranging from 0.3%to 9.6%.Using this method,actual sample tests were conducted on the Pearl River water,Zhaoqing pond water,and Qingyuan rice-fish aquaculture water.The total concentration of five neonicotinoid pesticides in the Pearl River water ranged from 154.8 to 246.6 ng/L,the total concentration of four neonicotinoid pesticides in the Zhaoqing pond water was 95.0-176.1 ng/L,and the total concentration of three neonicotinoid pesticides in the Qingyuan rice-fish aquaculture water was 2.3-11.7 ng/L.This method was simple in operation,highly sensitive,and had strong resistance to interference.It was suitable for detection of trace neonicotinoid pesticides in aquaculture water and could provide technical support for construction of a green aquaculture environment and resolution of international trade disputes.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

AIM To study the Chemical constituents from Rhinacanthus nasutus(L.)Kurz and their in vitro antitumor and lipid-lowering activities.METHODS The ethyl acetate fraction from R.nasutus was isolated and purified by normal phase,reverse phase silica gel column and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The in vitro anti-tumor activity was determined by MTT assay,and the in vitro lipid-lowering activity was evaluated by oleic acid-induced HepG2 high-fat cell model.RESULTS Twenty compounds were isolated and identified as rhinacanthin A(1),rhinacanthin B(2),rhinacanthin C(3),rhinacanthin D(4),rhinacanthin E(5),rhinacanthin M(6),rhinacanthin N(7),rhinacanthin Q(8),rhinacanthin T(9),rhinacanthone(10),β-sitosterol(11),gallic acid(12),vanillic acid(13),syringic acid(14),lapachol(15),umbelliferone(16),sambucunlin A(17),17α,21-dihydroxy-1,4-pregnadiene-3,11,20-trione,21-acetate(18),1,8-dihydroxyanthraquinone(19),2,6-dimethoxy-1,4-benzoquinone(20).Compounds 3 and 7 inhibited the proliferation of HepG2,Hela,A549 and H22 tumor cells with IC50 values of(0.66±0.17)-(3.22±0.49)μmol/L in a time-and concentration-dependent manner.Compounds 3,7 and 9 had a lipid clearance rate of more than 50%in oleic acid-induced HepG2 high-fat cells.CONCLUSION Compounds 16-20 are isolated from this plant for the first time.Compounds 3 and 7 have good in vitro anti-tumor activities,and 3,7,9 have good in vitro lipid-lowering activities.

Objective To explore the efficacy and safety of evolocumab in elderly patients with high-risk cardiovascular diseases.Methods A total of 153 patients with poor lipid control after conventional statin therapy who were hospitalized in the cardiologic departments in the First,Sec-ond,Sixth and Eighth Medical Centers of Chinese PLA General Hospital from November 2019 to November 2022 were included,and divided into non-elderly group(＜60 years old,46 cases),eld-erly group(60-74 years old,66 case)and very elderly group(≥75 years old,41 cases).They were all given evolocumab treatment according to guidelines.Another 50 over-75-year-old patients with high-risk cardiovascular diseases and poor lipid control who were hospitalized in the above cardiologic departments during the same period were treated with a statin drug combined with ezetimibe,and served as conventional treatment group(control group).The baseline clinical data and the blood indicators at 4th and 12th week after drug administration,and the occurrence of ad-verse drug reactions and major adverse cardiovascular events(MACE)within 12 weeks were com-pared among the groups.Results The levels of LDL-C and TC were significantly decreased in the three evolocumab treatment groups at 4 and 12 weeks after medication when compared with the baseline values(P＜0.05,P＜0.01),but there were no obvious differences in the 2 levels among the 3 groups at 12 weeks(P＞0.05).At the time point,no statistical difference was observed in the incidence of adverse events in the three groups(2.2％vs 3.0％vs 2.4％,P＞0.05).The levels of LDL-C and TC were decreased significantly in the very elderly group and the conventional treatment group at the 12th week when compared with the baseline levels(P＜0.05,P＜0.01),and the LDL-C level at the week was notably lower in the very elderly group than the convention-al treatment group(1.36±0.44 mmol/L vs 1.87±0.56 mmol/L,P＜0.01).But no difference was seen in the incidence of MACE between the 2 groups(12.2％vs 16.0％,P＞0.05),either in sur-vival rate between them(P=0.576).Conclusion For patients of all ages,evolocumab has good short-term efficacy in lipid control,and for those over 75 years old,the drug also shows good effi-cacy and sound safety.

Objective:To investigate the changes of hippocampal gray matter volume and expression of candidate immune related genes in a rat model of schizophrenia established by repeated administration of dizocilpine(MK-801).Methods:Thirty SPF grade Sprague-Dawley male rats at postnatal day 28 were randomly divided into MK-801 medium-dose (0.25 mg/kg) group, MK-801 high-dose(0.50 mg/kg) group and normal saline (5 mL/kg) group according to random number table method, with 10 in each group.Rats were given continuous intraperitoneal administration according to grouping once a day for 14 days.Open field test, novel object recognition test and Y-maze test were used at postnatal day 60 to detect spontaneous activity, exploration ability, anxiety level, object recognition memory ability and spatial working memory of rats, respectively.At postnatal day 67, structural magnetic resonance imaging was used to detect the changes of hippocampal gray matter volume in rat.And at postnatal day 70, qRT-PCR was used to detect the expression of candidate immune-related genes in rat hippocampus.SPSS 25.0 was used for statistical analysis, one-way ANOVA was used for comparison among multiple groups, and Tukey test was used for further pairwise comparisons.Results:(1)The behavioral results showed that there were significant differences in the total movement distance, central area activity time, novel object recognition index, and spontaneous correct alternation rate among the three groups ( F=11.15, 10.11, 13.62, 11.99, all P<0.05). The total movement distances in MK-801 medium-dose group and MK-801 high-dose group ((21.44±2.17) m, (22.87±1.96)m) were higher than that in the normal saline group ((18.70±1.88) m) (both P<0.05). The activity time of the central area in the MK-801 medium-dose group and MK-801 high-dose group((3.24±1.58) s, (2.50±1.32) s) were lower than that of the normal saline group ((6.05±2.48)s) (both P<0.01). Novel object recognition indexes in the MK-801 medium-dose group and MK-801 high-dose group((56.10±3.99)%, (54.00±6.41)%) were both lower than that in the normal saline group ((65.90±5.65)%)(both P<0.01), and the rates of spontaneous correct alternation ((54.60±7.03)%, (51.60±8.84)%) in the two groups were lower than that of the normal saline group ((68.40±8.57)%) (both P<0.01). (2) The results of structural magnetic resonance imaging showed that there were significant differences in the volume of hippocampal gray matter among the three groups ( F=9.24, P<0.001). The volumes of hippocampal gray matter in MK-801 medium-dose group and MK-801 high-dose group were lower than that in normal saline group(both P<0.001). (3)By constructing protein-protein interaction network, four candidate immune related genes were screened out: neuropeptide Y (NPY), somatostatin (SST), cholecystokinin (CCK) and tachykinin 1 (TAC1). The results showed that the mRNA expression levels of NPY, SST and CCK in the hippocampus of the three groups were significantly different ( F=11.41, 10.43, 5.85, all P<0.05), but there was no statistical difference in the TAC1 mRNA expression level ( F=0.08, P>0.05). The mRNA levels of NPY, SST and CCK in the hippocampus of rats in the MK-801 high-dose group were lower than those in the normal saline group (all P<0.05). Conclusion:Both medium dose and high dose MK-801 administration can reduce the volume of hippocampal gray matter in schizophrenia model rats, but they have different effects on the expression of hippocampal immune related genes, of which high dose administration has a greater effect.

Collagen is a macromolecular protein constituting the extracellular matrix of animal connective tissue, which has been widely used and developed in fields of biomedicine, tissue engineering, food, and cosmetics. Due to its advantages such as abundant sources and good biocompatibility, low immunogenicity, and degradability, collagen can be used as a dressing or tissue engineering scaffold for wound repair. According to the source of materials, collagen can be divided into natural collagen and recombinant collagen. Natural collagen is mainly extracted directly from mammals and fish; recombinant collagen is obtained based on genetic engineering technology, and its sources include recombinant expression systems of microorganisms, animals, and plants. This paper summarizes the sources of collagen, and the roles, advantages, and disadvantages of different sources of collagen in wound repair, the particularity and superiority of collagen combined with three-dimensional printing technology in wound repair, the impact of market norms of China's collagen industry on the field of wound repair, and explains the precautions for the development of collagen-related products, aiming to provide new ideas for selecting a suitable source of collagen for wound repair.
Animals ; Collagen/metabolism* ; Wound Healing ; Tissue Engineering ; Tissue Scaffolds ; Cosmetics ; Mammals/metabolism*

OBJECTIVE: To investigate the dynamic changes of macrophage numbers and apoptosis during Schistosoma japonicum infection, and to investigate the possible mechanisms of macrophage apoptosis induced by S. japonicum soluble egg antigen (SEA). METHODS: C57BL/6 mice at ages of 6~8 weeks were randomly divided into 4 groups, including three experimental groups and a normal control group. Each mouse in the experimental groups was infected with (12 ± 1) cercariae of S. japonicum via the abdominal skin, and all mice in an experimental group were sacrificed 3, 5, 8 weeks post-infection, respectively, while mice in the control group were not infected with S. japonicum cercariae and sacrificed on the day of S. japonicum infection in the experimental group. Mouse liver specimens and peritoneal exudation cells were sampled in each group, and the dynamic changes of macrophage numbers and apoptosis were detected. Mouse peritoneal macrophages were isolated, purified and treated with S. japonicum SEA, PBS and ovalbumin (OVA) in vitro, and the macrophage apoptosis was detected using flow cytometry. The mRNA and protein expression of BCL-2 protein family members were determined in macrophages using real-time quantitative PCR (qP-CR) and Western blotting assays, and the activation of caspase 3 was determined using flow cytometry and Western blotting. In addition, macrophages were in vitro treated with S. japonicum SEA in presence of a caspase inhibitor, H₂O₂ or N-acetyl-L-cysteine, and the apoptosis of macrophages was detected using flow cytometry. RESULTS: The total macrophage numbers continued to increase in mouse liver [(0.873 ± 0.106) × 106, (2.737 ± 0.460) × 10⁶ and (3.107 ± 0.367) × 10⁶ cells, respectively; F = 81.900, P < 0.01] and peritoneal specimens [(5.282 ± 1.136) × 105, (7.500 ± 1.200) × 10⁵ and (12.800 ± 0.800) × 10⁵ cells, respectively; F = 55.720, P < 0.01] 3, 5 and 8 weeks post-infection with S. japonicum, and the numbers of apoptotic macrophages also continued to increase in mouse liver [(0.092 ± 0.018) × 10⁶, (0.186 ± 0.025) × 10⁶ and (0.173 ± 0.0270) × 10⁶ cells; F = 57.780, P < 0.01] and peritoneal specimens [(0.335 ± 0.022) × 10⁵, (0.771 ± 0.099) × 10⁵ and (1.094 ± 0.051) × 10⁵ cells; F = 49.460, P < 0.01] 3, 5 and 8 weeks post-infection with S. japonicum. The apoptotic rate of SEA-treated macrophages [(24.330 ± 0.784)%] was significantly higher than that of PBS-[(18.500 ± 1.077)%] and OVA-treated macrophages [(18.900 ± 1.350)%] (both P values < 0.01). There were no significant differences in the mRNA or protein expression of Bcl-2 [Bcl - 2 mRNA expression: (1.662 ± 0.943) vs. (1.000 ± 0.000), t = 1.215, P > 0.05; BCL protein expression: (0.068 ± 0.004) vs. (0.070 ± 0.005), t = 0.699, P > 0.05], Bax [Bax mRNA expression: (0.711 ± 0.200) vs. (1.000 ± 0.000), t = 2.507, P > 0.05; BAX protein expression: (0.089 ± 0.005) vs. (0.097 ± 0.003), t = 2.232, P > 0.05] and Bak [Bak mRNA expression: (1.255 ± 0.049) vs. (1.00 ± 0.00), t = 0.897, P > 0.05; BAK protein expression: (0.439 ± 0.048) vs. (0.571 ± 0.091), t = 2.231, P > 0.05] between in SEA- and PBS-treated macrophages. S. japonicum SEA induced macrophage apoptosis in the presence of a caspase inhibitor (F = 0.411, P > 0.05); however, SEA failed to induce macrophage apoptosis in the presence of H₂O₂ or NAC (F = 11.880 and 9.897, both P values < 0.05). CONCLUSIONS S. japonicum SEA may induce macrophage apoptosis through promoting reactive oxygen species expression during S. japonicum infections in mice.
Animals ; Apoptosis ; Caspases ; Hydrogen Peroxide ; Macrophages ; Mice ; Mice, Inbred C57BL ; RNA, Messenger ; Schistosoma japonicum ; Schistosomiasis japonica ; bcl-2-Associated X Protein

Objective To establish bovine corneal opacity and permeability （BCOP） test， and determine its predictive ability for the eye irritation evaluation of cosmetics. Methods A total of ten reference chemicals were selected to establish the BCOP test. Then eye irritation of 16 routinely collected cosmetics in our laboratory was predicted. In vitro scores were calculated by the change in the opacity and sodium fluorescein permeability after exposure to the testing cosmetics， and subsequently compared with the historical data by Draize test. Results Reference chemicals with known irritation classification were correctly classified by the BCOP test， which was consistent with the classification of UN globally harmonized system of classification and labeling of chemicals. Moreover， the specificity of the BCOP test for the classification of non-irritating cosmetics samples was 80.0% （8/10）， and the sensitivity for weak to mild irritating cosmetics samples was 83.3% （5/6）. The BCOP test demonstrated an overall classification consistency of 81.3% （13/16） with in vivo test. Conclusion BCOP test may be independently used to identify chemicals with potential eye irritation and serious eye damage， suggesting it is significant for in vitro integrated test strategy for predicting eye irritation due to cosmetics.