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1.
Natl Sci Rev ; 11(7): nwae195, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39045468

ABSTRACT

Endogenous opioid antinociception is a self-regulatory mechanism that reduces chronic pain, but its underlying circuit mechanism remains largely unknown. Here, we showed that endogenous opioid antinociception required the activation of mu-opioid receptors (MORs) in GABAergic neurons of the central amygdala nucleus (CEA) in a persistent-hyperalgesia mouse model. Pharmacogenetic suppression of these CEAMOR neurons, which mimics the effect of MOR activation, alleviated the persistent hyperalgesia. Furthermore, single-neuron projection analysis revealed multiple projectome-based subtypes of CEAMOR neurons, each innervating distinct target brain regions. We found that the suppression of axon branches projecting to the parabrachial nucleus (PB) of one subtype of CEAMOR neurons alleviated persistent hyperalgesia, indicating a subtype- and axonal-branch-specific mechanism of action. Further electrophysiological analysis revealed that suppression of a distinct CEA-PB disinhibitory circuit controlled endogenous opioid antinociception. Thus, this study identified the central neural circuit that underlies endogenous opioid antinociception, providing new insight into the endogenous pain modulatory mechanisms.

2.
Heliyon ; 10(12): e33220, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-39021916

ABSTRACT

Seahorses are increasingly recognized for their nutritional potential, which underscores the necessity for comprehensive biochemical analyses. This study aims to investigate the fatty acid and amino acid compositions of eight seahorse species, including both genders of Hippocampus trimaculatus, Hippocampus kelloggi, Hippocampus abdominalis, and Hippocampus erectus, to evaluate their nutritional value. We employed Gas Chromatography-Mass Spectrometry (GC-MS) and High-Performance Liquid Chromatography (HPLC) to analyze the fatty acid and amino acid profiles of the seahorse species. GC-MS was used to detect 34 fatty acid methyl esters, while HPLC provided detailed amino acid profiles. GC-MS analysis demonstrated high precision with relative standard deviations (RSDs) generally below 2.53 %, satisfactory repeatability (RSDs from 6.55 % to 8.73 %), and stability (RSDs below 2.82 %). Recovery rates for major fatty acids ranged from 98.73 % to 109.12 %. HPLC analysis showed strong separation of amino acid profiles with theoretical plate numbers exceeding 5000. Precision tests yielded RSDs below 1.23 %, with reproducibility and stability tests showing RSDs below 2.73 % and 2.86 %, respectively. Amino acid recovery rates ranged from 97.58 % to 104.66 %. Nutritional analysis revealed significant variations in fatty acid content among the species. Female H. erectus showed higher levels of hexadecanoic acid and saturated fatty acids, while male H. abdominalis had lower concentrations of n-3 full cis 4,7,10,13,16,19-docosahexaenoic acid (DHA). Total lipid yields varied from 3.2491 % to 12.3175 %, with major fatty acids constituting 17.9717 %-74.6962 % of total lipids. In conclusion, this study provides essential insights into the fatty acid and amino acid composition of seahorses, supporting their potential as valuable dietary supplements. The differences between genders in specific fatty acids suggest a nuanced nutritional profile that could be exploited for targeted dietary applications. Further research is needed to explore the seasonal and environmental variations affecting seahorse biochemical composition.

3.
Heliyon ; 10(12): e33187, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-39021937

ABSTRACT

Quantifying and interpreting the water-energy-food (WEF) nexus is critical to achieve the sustainable development of urban resources. The mismatch between urban water, energy and food allocations is a prominent problem that is particularly acute in the Yellow River Basin (YRB) of China. In this study, models for the WEF coupling degree and coupling efficiency were constructed. The WEF coupling efficiencies of the 94 cities in the YRB from 2011 to 2020 were quantified using a data envelopment analysis (DEA) model. On this basis, the spatial distribution characteristics and evolutionary trends of different urban WEF coupling efficiencies were analysed and explored using an exploratory spatial data analysis (ESDA) model and a parametric kernel density estimation model. The results show that the energy subsystem constrain the development of the WEF nexus, and the food subsystem, in turn, regulates the development of the WEF nexus. In some years, the phenomenon of 'resource curse' occurred, in which the WEF coupling degree increased while the coupling efficiency decreased. Overall, the values of the urban WEF coupling efficiency were low, ranging from 0.5300 to 0.6300, which is not effective. Spatial clustering was detected in the urban WEF coupling efficiency. The clustering types were 'high-high' clustering areas in less developed regions and 'low-low' clustering areas in developed regions. The two clusters and the median contiguous group had different evolutionary trends. Both efficiency and polarisation increased in the high-clustering group, efficiency improved in the low-clustering group, and a new efficiency pole was formed in the median contiguous group. Among the three grouped cities, we discuss the potential of policies such as cross-city cooperation, intra-city multi-sectoral cooperation and cultivating new central growth cities to improve the WEF coupling efficiency in the YRB.

4.
J Exp Bot ; 2024 Jul 20.
Article in English | MEDLINE | ID: mdl-39031128

ABSTRACT

The plant cuticle is a complex extracellular lipid barrier that has multiple protective functions. We investigated cuticle deposition by integrating metabolomics and transcriptomics data gathered from six different maize seedling organs of four genotypes, the inbred lines B73 and Mo17, and their reciprocal hybrids. These datasets captured the developmental transition of the seedling from heterotrophic skotomorphogenic growth to autotrophic photomorphogenic growth, which is a transition that is highly vulnerable to environmental stresses. Statistical interrogation of these data reveals that the predominant determinant of cuticle composition is seedling organ type, whereas the seedling genotype has a smaller effect on this phenotype. Gene-to-metabolite associations assessed by integrated statistical analyses identified three gene networks connected with the deposition of different elements of the cuticle: a) cuticular waxes; b) monomers of lipidized cell wall biopolymers, including cutin and suberin; and c) both of these elements. These gene networks reveal three metabolic programs that appear to support cuticle deposition, including processes of chloroplast biogenesis, lipid metabolism, and molecular regulation (e.g., transcription factors, post-translational regulators and phytohormones). This study demonstrates the wider physiological metabolic context that can determine cuticle deposition and lays the groundwork for new targets for modulating properties of this protective barrier.

6.
Transl Psychiatry ; 14(1): 293, 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-39019862

ABSTRACT

Electronic cigarettes (e-cigs) use, especially among youngsters, has been on the rise in recent years. However, little is known about the long-term effects of the use of e-cigs on brain functional activity. We acquired the resting-state functional magnetic resonance imaging (rs-fMRI) data from 93 e-cigs users with nicotine dependence and 103 health controls (HC). The local synchronization was analyzed via the regional homogeneity (ReHo) method at voxel-wise level. The functional connectivity (FC) between the nucleus accumbens (NAcc), the ventral tegmental area (VTA), and the insula was calculated at ROI-wise level. The support vector machining classification model based on rs-fMRI measures was used to identify e-cigs users from HC. Compared with HC, nicotine-dependent e-cigs users showed increased ReHo in the right rolandic operculum and the right insula (p < 0.05, FDR corrected). At the ROI-wise level, abnormal FCs between the NAcc, the VTA, and the insula were found in e-cigs users compared to HC (p < 0.05, FDR corrected). Correlation analysis found a significant negative correlation between ReHo in the left NAcc and duration of e-cigs use (r = -0.273, p = 0.008, FDR corrected). The following support vector machine model based on significant results of rs-fMRI successfully differentiates chronic e-cigs users from HC with an accuracy of 73.47%, an AUC of 0.781, a sensitivity of 67.74%, and a specificity of 78.64%. Dysregulated spontaneous activity and FC of addiction-related regions were found in e-cigs users with nicotine dependence, which provides crucial insights into the prevention of its initial use and intervention for quitting e-cigs.


Subject(s)
Electronic Nicotine Delivery Systems , Magnetic Resonance Imaging , Nucleus Accumbens , Tobacco Use Disorder , Humans , Tobacco Use Disorder/physiopathology , Tobacco Use Disorder/diagnostic imaging , Male , Female , Adult , Nucleus Accumbens/diagnostic imaging , Nucleus Accumbens/physiopathology , Young Adult , Insular Cortex/diagnostic imaging , Insular Cortex/physiopathology , Ventral Tegmental Area/diagnostic imaging , Ventral Tegmental Area/physiopathology , Support Vector Machine , Case-Control Studies , Vaping/physiopathology
7.
Heliyon ; 10(12): e33072, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38994059

ABSTRACT

High-polarity iridoids from Radix Scrophulariae (R. Scrophulariae) offer a range of benefits, including anti-inflammatory, antioxidant, antitumour, antibacterial, antiviral, and antiallergic effects. Although previous studies have indicated the potential of R. Scrophulariae for hyperthyroidism prevention and treatment, the specific active compounds involved and their mechanisms of action are not fully understood. This study explored the effects of high-polarity iridoid glycosides from R. Scrophulariae on hyperthyroidism induced in rats by levothyroxine sodium. The experimental design included a control group, a hyperthyroidism model group, and a group treated with iridoid glycosides. Serum triiodothyronine (T3) and thyroxine (T4) levels were quantified using an enzyme-linked immunosorbent assay (ELISA). Transcriptomic and proteomic analyses were applied to liver samples to identify differentially expressed genes and proteins. These analyses were complemented by trend analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The effectiveness of key factors was further examined through molecular biology techniques. ELISA results indicated a notable increase in T3 and T4 in the hyperthyroid rats, which was significantly mitigated by treatment with iridoid glycosides. Transcriptomic analysis revealed 6 upregulated and 6 downregulated genes in the model group, showing marked improvement following treatment. Proteomic analysis revealed changes in 30 upregulated and 50 downregulated proteins, with improvements observed upon treatment. The PI3K-Akt signalling pathway was investigated through KEGG enrichment analysis. Molecular biology methods verified the upregulation of Spp1, Thbs1, PI3K, and Akt in the model group, which was reversed in the treatment group. This study revealed that highly polar iridoids from R. Scrophulariae can modulate the Spp1 gene and Thbs1 protein via the PI3K-Akt signalling pathway, suggesting a therapeutic benefit for hyperthyroidism and providing a basis for drug development targeting this condition.

8.
Clin Res Cardiol ; 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39009912

ABSTRACT

BACKGROUND: Current guidelines on the management strategy for patients with asymptomatic severe aortic stenosis (AS) remain unclear. This uncertainty stems from the lack of data regarding the natural history of these patients. To address this gap, we performed a systematic review and meta-analysis examining the natural history of asymptomatic severe AS patients receiving conservative treatment. METHODS: The PubMed, Cochrane, and Embase databases were searched from inception to 24 January 2024 using the keywords "asymptomatic" AND "aortic" AND "stenosis". We included studies examining patients with asymptomatic severe AS. In interventional trials, only data from conservatively managed arms were collected. A one-stage meta-analysis was conducted using individual patient data reconstructed from published Kaplan-Meier curves. Sensitivity analysis was performed for major adverse cardiovascular outcomes in patients who remained asymptomatic throughout follow-up. RESULTS: A total of 46 studies were included (n = 9545). The median time to the development of symptoms was 1.11 years (95% CI 0.90-1.53). 49.36% (40.85-58.59) of patients who were asymptomatic had suffered a major adverse cardiovascular event by 5 years. The median event-free time for heart failure hospitalization (HFH) was 5.50 years (95% CI 5.14-5.91) with 36.34% (95% CI 33.34-39.41) of patients experiencing an HFH by year 5. By 5 years, 79.81% (95% CI 69.26-88.58) of patients developed symptoms (angina, dyspnoea, syncope and others) and 12.36% (95% CI 10.01-15.22) of patients died of cardiovascular causes. For all-cause mortality, the median survival time was 9.15 years (95% CI 8.50-9.96) with 39.43% (CI 33.41-36.40) of patients dying by 5 years. The median time to AVR was 4.77 years (95% CI 4.39-5.17), with 52.64% (95% CI 49.85-55.48) of patients requiring an AVR by 5 years. CONCLUSION: Our results reveal poor cardiovascular outcomes for patients with asymptomatic severe AS on conservative treatment. A significant proportion eventually requires an AVR. Further research is needed to determine if early intervention with AVR is more effective than conservative treatment.

9.
Cell Rep ; 43(8): 114527, 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-39046873

ABSTRACT

The paracrine actions of adipokine plasminogen activator inhibitor-1 (PAI-1) are implicated in obesity-associated tumorigenesis. Here, we show that PAI-1 mediates extracellular matrix (ECM) signaling via epigenetic repression of DKK1 in endometrial epithelial cells (EECs). While the loss of DKK1 is known to increase ß-catenin accumulation for WNT signaling activation, this epigenetic repression causes ß-catenin release from transmembrane integrins. Furthermore, PAI-1 elicits the disengagement of TIMP2 and SPARC from integrin-ß1 on the cell surface, lifting an integrin-ß1-ECM signaling constraint. The heightened interaction of integrin-ß1 with type 1 collagen (COL1) remodels extracellular fibrillar structures in the ECM. Consequently, the enhanced nanomechanical stiffness of this microenvironment is conducive to EEC motility and neoplastic transformation. The formation of extensively branched COL1 fibrils is also observed in endometrial tumors of patients with obesity. The findings highlight PAI-1 as a contributor to enhanced integrin-COL1 engagement and extensive ECM remodeling during obesity-associated neoplastic development.

10.
Sensors (Basel) ; 24(13)2024 Jul 05.
Article in English | MEDLINE | ID: mdl-39001146

ABSTRACT

This study develops a model to assess building vulnerability across Xinxing County by integrating quantitative derivation with machine learning techniques. Building vulnerability is characterized as a function of landslide hazard risk and building resistance, wherein landslide hazard risk is derived using CNN (1D) for nine hazard-causing factors (elevation, slope, slope shape, geotechnical body type, geological structure, vegetation cover, watershed, and land-use type) and landslide sites; building resistance is determined through quantitative derivation. After evaluating the building susceptibility of all the structures, the susceptibility of each village is then calculated through subvillage statistics, which are aimed at identifying the specific needs of each area. Simultaneously, different landslide hazard classes are categorized, and an analysis of the correlation between building resistance and susceptibility reveals that building susceptibility exhibits a positive correlation with landslide hazard and a negative correlation with building resistance. Following a comprehensive assessment of building susceptibility in Xinxing County, a sample encompassing different landslide intensity areas and susceptibility classes of buildings was chosen for on-site validation, thus yielding an accuracy rate of the results as high as 94.5%.

11.
Microbiome ; 12(1): 123, 2024 Jul 06.
Article in English | MEDLINE | ID: mdl-38971798

ABSTRACT

BACKGROUND: The Atribacterota are widely distributed in the subsurface biosphere. Recently, the first Atribacterota isolate was described and the number of Atribacterota genome sequences retrieved from environmental samples has increased significantly; however, their diversity, physiology, ecology, and evolution remain poorly understood. RESULTS: We report the isolation of the second member of Atribacterota, Thermatribacter velox gen. nov., sp. nov., within a new family Thermatribacteraceae fam. nov., and the short-term laboratory cultivation of a member of the JS1 lineage, Phoenicimicrobium oleiphilum HX-OS.bin.34TS, both from a terrestrial oil reservoir. Physiological and metatranscriptomics analyses showed that Thermatribacter velox B11T and Phoenicimicrobium oleiphilum HX-OS.bin.34TS ferment sugars and n-alkanes, respectively, producing H2, CO2, and acetate as common products. Comparative genomics showed that all members of the Atribacterota lack a complete Wood-Ljungdahl Pathway (WLP), but that the Reductive Glycine Pathway (RGP) is widespread, indicating that the RGP, rather than WLP, is a central hub in Atribacterota metabolism. Ancestral character state reconstructions and phylogenetic analyses showed that key genes encoding the RGP (fdhA, fhs, folD, glyA, gcvT, gcvPAB, pdhD) and other central functions were gained independently in the two classes, Atribacteria (OP9) and Phoenicimicrobiia (JS1), after which they were inherited vertically; these genes included fumarate-adding enzymes (faeA; Phoenicimicrobiia only), the CODH/ACS complex (acsABCDE), and diverse hydrogenases (NiFe group 3b, 4b and FeFe group A3, C). Finally, we present genome-resolved community metabolic models showing the central roles of Atribacteria (OP9) and Phoenicimicrobiia (JS1) in acetate- and hydrocarbon-rich environments. CONCLUSION: Our findings expand the knowledge of the diversity, physiology, ecology, and evolution of the phylum Atribacterota. This study is a starting point for promoting more incisive studies of their syntrophic biology and may guide the rational design of strategies to cultivate them in the laboratory. Video Abstract.


Subject(s)
Carbon , Oil and Gas Fields , Phylogeny , Carbon/metabolism , Oil and Gas Fields/microbiology , RNA, Ribosomal, 16S/genetics , Genome, Bacterial , Alkanes/metabolism
12.
J Environ Manage ; 366: 121718, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38971064

ABSTRACT

Pyrite (FeS2) has garnered attention due to its narrow bandgap, high light absorption, and low cost. However, the rapid recombination of charge carriers hinders its practical application. Surface electric field is a unique characteristic of tourmaline, which can induce effective separation of photo generated electrons and holes. This study successfully combined two directly mined natural minerals, tourmaline and pyrite, to form TFS. Characterization and experiments show that the surface electric field of tourmaline can significantly enhance the photocatalytic activity of TFS. Tetracycline (TC, 50 ppm) was degraded by 95% with 60 min, and the TFS reaction rate constant reached 0.0439 min-1, which is 6.1 times and 17.3 times higher than that of tourmaline and FeS2. Additionally, it significantly improved light absorption and charge carrier separation capabilities. After simulating various natural environmental factors, TFS demonstrated practicality. Considered analysis of active substances and detection revealed that h+ and 1O2 radicals are significant contributors, and the photocatalytic mechanism was proposed. Furthermore, the transformation pathways and toxicity of metabolites were studied. This research offers further inspiration and insights for improving photocatalytic material performance and the green governance environment of natural resources.

14.
Nat Food ; 5(7): 563-568, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38951691

ABSTRACT

Healthy dietary patterns, such as the alternate Mediterranean diet and alternate Healthy Eating Index, benefit cardiometabolic health. However, several food components of these dietary patterns are primary sources of environmental chemicals. Here, using data from a racially and ethnically diverse US cohort, we show that healthy dietary pattern scores were positively associated with plasma chemical exposure in pregnancy, particularly for the alternate Mediterranean diet and alternate Healthy Eating Index with polychlorinated biphenyls and per- and poly-fluoroalkyl substances. The associations appeared stronger among Asian and Pacific Islanders. These findings suggest that optimizing the benefits of a healthy diet requires concerted regulatory efforts aimed at lowering environmental chemical exposure.


Subject(s)
Environmental Exposure , Environmental Pollutants , Polychlorinated Biphenyls , Humans , Female , Pregnancy , Adult , Environmental Pollutants/blood , Environmental Exposure/adverse effects , Cohort Studies , Polychlorinated Biphenyls/blood , Diet, Healthy , Diet, Mediterranean , United States/epidemiology , Young Adult , Dietary Patterns
15.
J Med Virol ; 96(7): e29768, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38978388

ABSTRACT

The vagus nerve circuit, operating through the alpha-7 nicotinic acetylcholine receptor (α7 nAChR), regulates the inflammatory response by influencing immune cells. However, the role of vagal-α7 nAChR signaling in influenza virus infection is unclear. In particular, does vagal-α7 nAChR signaling impact the infection of alveolar epithelial cells (AECs), the primary target cells of influenza virus? Here, we demonstrated a distinct role of α7 nAChR in type II AECs compared to its role in immune cells during influenza infection. We found that deletion of Chrna7 (encoding gene of α7 nAChR) in type II AECs or disruption of vagal circuits reduced lung influenza infection and protected mice from influenza-induced lung injury. We further unveiled that activation of α7 nAChR enhanced influenza infection through PTP1B-NEDD4L-ASK1-p38MAPK pathway. Mechanistically, activation of α7 nAChR signaling decreased p38MAPK phosphorylation during infection, facilitating the nuclear export of influenza viral ribonucleoproteins and thereby promoting infection. Taken together, our findings reveal a mechanism mediated by vagal-α7 nAChR signaling that promotes influenza viral infection and exacerbates disease severity. Targeting vagal-α7 nAChR signaling may offer novel strategies for combating influenza virus infections.


Subject(s)
Lung , Orthomyxoviridae Infections , Signal Transduction , Vagus Nerve , alpha7 Nicotinic Acetylcholine Receptor , Animals , alpha7 Nicotinic Acetylcholine Receptor/metabolism , alpha7 Nicotinic Acetylcholine Receptor/genetics , Vagus Nerve/metabolism , Mice , Orthomyxoviridae Infections/virology , Lung/virology , Lung/pathology , Mice, Inbred C57BL , Alveolar Epithelial Cells/virology , Alveolar Epithelial Cells/metabolism , Humans , Mice, Knockout
16.
Chem Commun (Camb) ; 60(61): 7922-7925, 2024 Jul 25.
Article in English | MEDLINE | ID: mdl-38982934

ABSTRACT

A ferrocene-modified COF, namely Ni-Tph-COF-Fc, was synthesized and applied in OER. Compared with Ni-Tph-COF-OH, Ni-Tph-COF-Fc shows improved performance with a current density of 99.6 mA cm-2, an overpotential of 450 mV, and a Tafel slope of 73.1 mV dec-1, which may be attributed to a synergy between introduced ferrocene and metalloporphyrin in the COFs. Moreover, the enhanced OER performance leads to an improved CO2RR performance with an FECO of 93.1%. This work represents an effective strategy to enhance the anodic OER performance and realize efficient CO2RR.

17.
Heliyon ; 10(13): e33695, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39044968

ABSTRACT

The water quality index (WQI) is a widely used tool for comprehensive assessment of river environments. However, its calculation involves numerous water quality parameters, making sample collection and laboratory analysis time-consuming and costly. This study aimed to identify key water parameters and the most reliable prediction models that could provide maximum accuracy using minimal indicators. Water quality from 2020 to 2023 were collected including nine biophysical and chemical indicators in seventeen rivers in Yancheng and Nantong, two coastal cities in Jiangsu Province, China, adjacent to the Yellow Sea. Linear regression and seven machine learning models (Artificial Neural Network (ANN), Self-Organizing Maps (SOM), K-Nearest Neighbor (KNN), Support Vector Machines (SVM), Random Forest (RF), Extreme Gradient Boosting (XGB) and Stochastic Gradient Boosting (SGB)) were developed to predict WQI using different groups of input variables based on correlation analysis. The results indicated that water quality improved from 2020 to 2022 but deteriorated in 2023, with inland stations exhibiting better conditions than coastal ones, particularly in terms of turbidity and nutrients. The water environment was comparatively better in Nantong than in Yancheng, with mean WQI values of approximately 55.3-72.0 and 56.4-67.3, respectively. The classifications "Good" and "Medium" accounted for 80 % of the records, with no instances of "Excellent" and 2 % classified as "Bad". The performance of all prediction models, except for SOM, improved with the addition of input variables, achieving R2 values higher than 0.99 in models such as SVM, RF, XGB, and SGB. The most reliable models were RF and XGB with key parameters of total phosphorus (TP), ammonia nitrogen (AN), and dissolved oxygen (DO) (R2 = 0.98 and 0.91 for training and testing phase) for predicting WQI values, and RF using TP and AN (accuracy higher than 85 %) for WQI grades. The prediction accuracy for "Medium" and "Low" water quality grades was highest at 90 %, followed by the "Good" level at 70 %. The model results could contribute to efficient water quality evaluation by identifying key water parameters and facilitating effective water quality management in river basins.

18.
Zhongguo Zhong Yao Za Zhi ; 49(11): 3061-3069, 2024 Jun.
Article in Chinese | MEDLINE | ID: mdl-39041166

ABSTRACT

In order to study the toxic effect and mechanism of triptolide(TP) on the reproductive system of female rats with Ⅱ type collagen induced arthritis(CIA), 50 SD rats were randomly divided into normal control group, CIA model group, and three groups receiving TP tablets at clinically equivalent doses of 0. 5, 1, and 2 times, respectively(with TP dosages of 3. 75, 7. 5, and 15 µg·kg~(-1)·d~(-1)), each comprising 10 rats. Intragastric administration was started on the day after the first immunization, once a day, for 42 days.The results were taken on the 21st and 42nd days to calculate the uterine and ovarian organ indexes; pathological and morphological changes in uterus and ovaries were observed under a light microscope; and the levels of estradiol(E_2) and cytochrome P450A1(aromatase,CYP19A1) in ovarian homogenate were detected by ELISA. Furthermore, immunohistochemistry was employed to detect the expression levels of transforming growth factor ß3( TGFß3) pathway-related proteins, mothers against decapentaplegic homolog 3(Smad3) and steroidogenic factor-1(SF-1) in ovarian tissues. In vitro, the mouse Chinese hamster ovary(CHO) cell line was established, and after 24 hours of TP administration(30, 60, 120 nmol·L~(-1)), cell proliferation was detected by the thiazolyl blue tetrazolium bromide(MTT) method, apoptosis by the flow cytometry, and TGFß3, Smad3 and SF-1 protein expression in cells by the Western blot method, and the nuclear entry of SF-1 was detected by immunofluorescence. The results showed that compared with the CIA model group, all TP administration groups showed decreased number of uterine glands, total follicles, mature follicles, and corpus luteum on days 21 and 42 of administration, but there was no statistical difference, and only the administration of 2 times the clinically equivalent dose of TP could significantly increase the number of atretic follicles at 42 days of administration. TP at 3. 75 µg·kg-1·d-1significantly reduced the level of E_2 at 21 days of administration and the expression of TGFß3 and Smad3 factors in ovarian tissues,but had no significant effect on the rate-limiting enzyme in estrogen synthesis CYP19A1. TP at 7. 5 and 15 µg·kg~(-1)·d~(-1) significantly reduced the expression of SF-1 regardless of administration for 21 days or 42 days. TP can significantly promote ovarian cell apoptosis in vitro, with apoptosis mainly concentrated in the late stage of apoptosis after 24 hours of administration. In addition, 60 nmol·L~(-1) TP significantly reduced the protein expression of TGFß3, Smad3 and SF-1 in a dose-dependent manner. In summary, intragastric administration of TP at less than 2 times the clinically equivalent dose for 21 days and 42 days did not cause obvious reproductive damage to the uterus and ovarian tissues of CIA rats, and the number of atretic follicles changed significantly only when the 2 times the clinically equivalent dose was administered for 42 days. TP exerted reproductive toxicity in vivo on reproductive target organs and in vitro on ovarian cells by inhibiting the expression of TGFß3/Smad3/SF-1 pathway.


Subject(s)
Diterpenes , Epoxy Compounds , Ovary , Phenanthrenes , Rats, Sprague-Dawley , Uterus , Animals , Female , Diterpenes/pharmacology , Phenanthrenes/toxicity , Rats , Epoxy Compounds/toxicity , Epoxy Compounds/administration & dosage , Ovary/drug effects , Ovary/metabolism , Uterus/drug effects , Uterus/metabolism , Collagen Type II/metabolism , Smad3 Protein/metabolism , Smad3 Protein/genetics , Humans , Reproduction/drug effects , Arthritis, Experimental/drug therapy , Arthritis, Experimental/metabolism , Estradiol
20.
Can J Ophthalmol ; 2024 Jul 20.
Article in English | MEDLINE | ID: mdl-39043258

ABSTRACT

OBJECTIVE: To investigate the efficacy and safety of femtosecond laser-assisted cataract surgery (FLACS) compared with conventional phacoemulsification cataract surgery (CPCS). METHODS: Randomized controlled trials (RCTs) were systematically searched in PubMed, Embase, Cochrane Library, ClinicalTrials.gov, CNKI, and Wanfang. Main outcomes were visual acuity, capsulotomy parameters, effective lens position, and complications. Secondary outcomes included refractive outcomes, intraoperative parameters, and corneal parameters. RESULTS: In total, 41 RCTs involving 9310 eyes were included. There was a statistically significant difference in favour of FLACS over CPCS for uncorrected distance visual acuity at 12 months (mean difference [MD] -0.03; 95% CI -0.05 to -0.01); corrected distance visual acuity at 1 week (MD -0.05; 95% CI -0.07 to -0.02) and 12 months (MD -0.02; 95% CI -0.04 to -0.00); area of capsulotomy at 1 month (MD 4.04 mm2; 95% CI 3.45-4.64) and 6 months (MD 5.02 mm2; 95% CI 3.28-6.77); and intraocular lens centroid-pupil centroid distance at 1 week (MD -0.06 mm; 95% CI -0.08 to -0.05), 1 month (MD -0.07 mm; 95% CI -0.09 to -0.06), and 6 months (MD -0.06 mm; 95% CI -0.07 to -0.04). With regard to surgical complications, FLACS was less than CPCS for the incidence of decentred IOL (odds ratio 0.06; 95% CI 0.01-0.24). However, FLACS did not increase the incidence of other intraoperative or postoperative complications except subconjunctival hemorrhage. CONCLUSIONS: Both FLACS and CPCS are effective and safe. FLACS achieves better visual outcomes in the early postoperative period and long-term follow-up, accompanied by more accurate capsulotomy and more optimized effective lens position than CPCS. However, no difference of visual outcomes was found after middle-term follow-up.

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