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1.
J Sports Sci ; : 1-9, 2024 Sep 11.
Article in English | MEDLINE | ID: mdl-39259267

ABSTRACT

To investigate the associations of fundamental movement skill (FMS) proficiency with family factors, including socioeconomic status (SES) and caregiver characteristics, by sex in young children in China. Participants included 1,207 Chinese children aged 3-6 years in this cross-sectional study. Children's FMS, consisting of locomotor skills and object control (OC) skills, were assessed. Information on family SES and caregiver characteristics was reported by the parents. Sex differences in outcomes and the associations of FMS with family factors by sex were examined using SPSS 26.0. Boys scored significantly higher than girls in terms of overall FMS and OC skills (both p < 0.01). There were significant and negative associations between children's FMS and parental education level and parental body mass index (BMI), which varied by sex. Boys who were regularly cared for by parents had higher FMS and OC skill scores than did those who were primarily looked after by grandparents (both p < 0.01). This complex interplay between sex and family factors (i.e. parental education level, parental BMI, and the identity of primary caregiver) on FMS proficiency in young children underscores the urgent need for developing sex-tailored, family-involved, and socio-culturally adapted interventions to enhance FMS proficiency at the preschool stage.

2.
Curr Med Imaging ; 2024 Sep 10.
Article in English | MEDLINE | ID: mdl-39257154

ABSTRACT

OBJECTIVE: This study aimed to establish a multimodal deep-learning network model to enhance the diagnosis of benign and malignant pulmonary ground glass nodules [GGNs]. METHODS: Retrospective data on pulmonary GGNs were collected from multiple centers across China, including North, Northeast, Northwest, South, and Southwest China. The data were divided into a training set and a validation set in an 8:2 ratio. In addition, a GGN dataset was also obtained from our hospital database and used as the test set. All patients underwent chest computed tomography [CT], and the final diagnosis of the nodules was based on postoperative pathological reports. The Residual Network [ResNet] was used to extract imaging data, the Word2Vec method for semantic information extraction, and the Self Attention method for combining imaging features and patient data to construct a multimodal classification model. Then, the diagnostic efficiency of the proposed multimodal model was compared with that of existing ResNet and VGG models and radiologists. RESULTS: The multicenter dataset comprised 1020 GGNs, including 265 benign and 755 malignant nodules, and the test dataset comprised 204 GGNs, with 67 benign and 137 malignant nodules. In the validation set, the proposed multimodal model achieved an accuracy of 90.2%, a sensitivity of 96.6%, and a specificity of 75.0%, which surpassed that of the VGG [73.1%, 76.7%, and 66.5%] and ResNet [78.0%, 83.3%, and 65.8%] models in diagnosing benign and malignant nodules. In the test set, the multimodal model accurately diagnosed 125 [91.18%] malignant nodules, outperforming radiologists [80.37% accuracy]. Moreover, the multimodal model correctly identified 54 [accuracy, 80.70%] benign nodules, compared to radiologists' accuracy of 85.47%. The consistency test comparing radiologists' diagnostic results with the multimodal model's results in relation to postoperative pathology showed strong agreement, with the multimodal model demonstrating closer alignment with gold standard pathological findings [Kappa=0.720, P<0.01]. CONCLUSION: The multimodal deep learning network model exhibited promising diagnostic effectiveness in distinguishing benign and malignant GGNs and, therefore, holds potential as a reference tool to assist radiologists in improving the diagnostic accuracy of GGNs, potentially enhancing their work efficiency in clinical settings.

3.
Front Plant Sci ; 15: 1453823, 2024.
Article in English | MEDLINE | ID: mdl-39258294

ABSTRACT

The real-time monitoring of corn yield by a combine harvester is a critical data source for constructing the yield histogram, which significantly benefits precision management and decision-making in modern precision agriculture. While widely used, the current photoelectric sensor-based yield monitoring method has limitations. It detects the corn height on each scraper and calculates the yield through a geometric formula. However, it neglects the noticeable difference in the corn stacking patterns affected by factors such as feeding volume, terrain, and driving speed. This oversight often results in low accuracy and poor stability in the prediction of corn yield, highlighting the need for a more advanced approach. To resolve this, we employ EDEM discrete element simulation to demonstrate the large difference of corn stacking patterns on the scraper of the elevator corresponding to feeding volume. Then, we develop a real-time monitoring system on our self-developed double elevator testing rig for carrying out a composite dataset for training three machine learning algorithm-based models, namely Deep Neural Networks (DNN), Gradient Boosting Machine (GBM), and Random Forest (RF). Importantly, these models have undergone rigorous validation under various feeding volumes, ensuring their robustness and reliability. The auxiliary elevator speed is meticulously set at 150r/min, 225r/min, and 450r/min, providing a comprehensive performance assessment. The results denote that the DNN model performs best and is stable, with a coefficient of determination (R2) of 0.998, root mean square error (RMSE) of 0.526, and mean absolute error (MAE) of 0.425. The paper also performs field experiments to test the proposed three prediction models and the system. The results also denote the DNN-based prediction model's best performance for the lowest relative error of 2.29% and the highest average accuracy of 97.85%. Consequently, the proposed real-time corn yield monitoring system achieves high accuracy and reliability for the combine harvester applications.

4.
Plants (Basel) ; 13(15)2024 Jul 23.
Article in English | MEDLINE | ID: mdl-39124137

ABSTRACT

The karst area has become a high-risk area for Cadmium (Cd) exposure. Interestingly, the high levels of Cd in soils do not result in an excessive bioaccumulation of Cd in rice. Carbonate rock dissolution ions (CRIs) could limit the accumulation and translocation of Cd in rice. CRIs can become a major bottleneck in the remediation and management of farmlands in karst areas. However, there is limited research on the effects of CRIs in soils on Cd accumulation in rice. The karst area of lime soil (LS) and the non-karst areas of yellow soil (YS) were collected, and an external Cd was added to conduct rice cultivation experiments. Cd and CRIs (Ca2+, Mg2+, CO32-/HCO3-, and OH-) in the rice-soil system were investigated from the grain-filling to maturity periods. The results showed that CRIs of LS were significantly higher than that of YS in different treatments. CRIs of LS were 2.05 mg·kg-1 for Ca2+, 0.90 mg·kg-1 for Mg2+, and 42.29 mg·kg-1 for CO32- in LS. CRIs could influence DTPA Cd, resulting in DTPA Cd of LS being lower than that of YS. DTPA Cd of YS was one to three times larger than that of YS. Cd content in different parts of rice in YS was higher than that of LS. Cd in rice grains of YS was one to six times larger than that of LS. The uptake of Cd from the soil during Filling III was critical in determining rice Cd accumulation. CRIs in the soil could affect Cd accumulation in rice. Ca2+ and Mg2+ had significant negative effects on Cd accumulation of rice at maturity and filling, respectively. CO32-/HCO3- and OH- had significant negative effects on DTPA Cd in soil.

5.
Fitoterapia ; 178: 106190, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-39153556

ABSTRACT

Three new neo-5,10-seco-clerodane diterpenoids (1-3), four previously undescribed ethoxy/methoxy acetal analogues (4-7), one new etherified labdane diterpenoid (8), and seven known diterpenoids (9-15) were isolated from the whole plant of Schnabelia terniflora. Their structures were established on the basis of extensive spectroscopic analysis, single-crystal X-ray diffraction data, calculated electronic circular dichroism (ECD), and Mo2(OAc)4-induced circular dichroism. Compounds 2 and 3 represent the first examples of neo-5,10-seco-clerodane diterpenoids containing a 1H-pyrrole-2,5-dione and a pyrrolidine-2,5-dione moiety, respectively. A plausible biosynthetic pathway for 1-3 is proposed. All diterpenoids were evaluated for their cytotoxic activity against non-small-cell lung cancer lines (A549 and H460) and gastric cancer lines (HGC27 and AGS). Among them, 2 and 14 showed moderate cytotoxicity against four cell lines.

6.
Adv Mater ; 36(35): e2403088, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39003616

ABSTRACT

3D printing polymer or metal can achieve complicated structures while lacking multifunctional performance. Combined printing of polymer and metal is desirable and challenging due to their insurmountable mismatch in melting-point temperatures. Here, a novel volume-metallization 3D-printed polymer composite (VMPC) with bicontinuous phases for enabling coupled structure and function, which are prepared by infilling low-melting-point metal (LM) to controllable porous configuration is reported. Based on vacuum-assisted low-pressure conditions, LM is guided by atmospheric pressure action and overcomes surface tension to spread along the printed polymer pore channel, enabling the complete filling saturation of porous structures for enhanced tensile strength (up to 35.41 MPa), thermal (up to 25.29 Wm-1K-1) and electrical (>106 S m-1) conductivities. The designed 3D-printed microstructure-oriented can achieve synergistic anisotropy in mechanics (1.67), thermal (27.2), and electrical (>1012) conductivities. VMPC multifunction is demonstrated, including customized 3D electronics with elevated strength, electromagnetic wave-guided transport and signal amplification, heat dissipation device for chip temperature control, and storage components for thermoelectric generator energy conversion with light-heat-electricity.

7.
Microb Cell Fact ; 23(1): 179, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38890717

ABSTRACT

BACKGROUND: Human lysozyme (hLYZ) is a natural antibacterial protein with broad applications in food and pharmaceutical industries. Recombinant production of hLYZ in Komagataella phaffii (K. phaffii) has attracted considerable attention, but there are very limited strategies for its hyper-production in yeast. RESULTS: Here through Atmospheric and Room Temperature Plasma (ARTP)-based mutagenesis and transcriptomic analysis, the expression of two genes MYO1 and IQG1 encoding the cytokinesis core proteins was identified downregulated along with higher hLYZ production. Deletion of either gene caused severe cytokinesis defects, but significantly enhanced hLYZ production. The highest hLYZ yield of 1,052,444 ± 23,667 U/mL bioactivity and 4.12 ± 0.11 g/L total protein concentration were obtained after high-density fed-batch fermentation in the Δmyo1 mutant, representing the best production of hLYZ in yeast. Furthermore, O-linked mannose glycans were characterized on this recombinant hLYZ. CONCLUSIONS: Our work suggests that cytokinesis-based morphology engineering is an effective way to enhance the production of hLYZ in K. phaffii.


Subject(s)
Muramidase , Recombinant Proteins , Saccharomycetales , Muramidase/metabolism , Muramidase/genetics , Muramidase/biosynthesis , Recombinant Proteins/biosynthesis , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , Saccharomycetales/metabolism , Saccharomycetales/genetics , Humans , Fermentation , Cytokinesis , Metabolic Engineering/methods , Batch Cell Culture Techniques
8.
Abdom Radiol (NY) ; 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38829394

ABSTRACT

BACKGROUND: Determining whether prompt surgery is required for patient with ingested foreign bodies is clinically important. PURPOSE: To evaluate the potential value of computed tomography (CT) in guiding the selection of surgical treatment for patients with ingested foreign bodies in the lower gastrointestinal tract. METHODS: Between January 2014 and December 2023, we analyzed the data of 58 patients (median age: 65.4 years; range, 31-96 years) with ingested foreign bodies in the lower gastrointestinal tract who underwent CT examinations. Patients were treated either conservatively (35 cases) or surgically (23 cases). The angle between the long axis of the foreign body and the intestinal canal (FB-IC angle) was measured. CT findings and clinical variables were evaluated to identify potential indicators for surgical treatment through univariate and multivariate logistic regression analyses. RESULTS: Univariate analysis revealed the FB-IC angle (P = 0.002), presence of free peritoneal gas (P = 0.002), white blood cell count (P = 0.018), and neutrophil count (P = 0.007) as significant factors associated with surgical treatment. Multivariate analysis demonstrated that the FB-IC angle (odds ratio, 1.033; P = 0.045) and the presence of free peritoneal gas (odds ratio, 41.335; P = 0.002) are independent indicators for surgical management. The FB-IC angle showed an area under the receiver operating characteristic curve of 0.755, with a cutoff value of 51.25 degrees. CONCLUSION: The FB-IC angle and presence of free peritoneal gas serve as potential predictive imaging markers for surgical intervention.

9.
Mar Pollut Bull ; 203: 116424, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38692004

ABSTRACT

Bloom-induced macroalgal enrichment on the seafloor can substantially facilitate dissolved sulfide (DS) production through sulfate reduction. The reaction of DS with sedimentary reactive iron (Fe) is the main mechanism of DS consumption, which however usually could not effectively prevent DS accumulation caused by pulsed macroalgal enrichment. Here we used incubations to investigate the performance of Fe-rich red soil for buffering of DS produced from macroalgae (Ulva prolifera)-enriched sediment. Based on our results, a combination of red soil additions (6.8 kg/m2) before and immediately after pulsed macroalgal deposition (455 g/m2) can effectively cap DS within the red soil layer. The effective DS buffering is mainly due to ample Fe-oxide surface sites available for reaction with DS. Only a small loss (4 %) of buffering capacity after 18-d incubation suggests that the red soil is capable of prolonged DS buffering in macroalgae-enriched sediments.


Subject(s)
Geologic Sediments , Iron , Soil , Sulfides , Ulva , Sulfides/analysis , Geologic Sediments/chemistry , Soil/chemistry , Seaweed , Edible Seaweeds
10.
Aging (Albany NY) ; 16(10): 8667-8686, 2024 05 16.
Article in English | MEDLINE | ID: mdl-38761174

ABSTRACT

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary liver cancer worldwide. Cancer cells' local infiltration, proliferation, and spread are mainly influenced by the protein hydrolyzing function of different matrix metalloproteinases (MMPs). However, no study has determined the relationship between MMPs and prognostic prediction in HCC. METHODS: Expression profiles of mRNA and MMPs-related genes were obtained from publicly available databases. Cox regression and LASSO Cox regression analysis were used to identify and predict MMPs-related prognostic signature and construct predictive models for overall survival (OS). A nomogram was used to validate the accuracy of the prediction model. Drug prediction was performed using the Genomics of Drug Sensitivity in Cancer (GDSC) dataset, and single-cell clustering analysis was performed to further understand the significance of the MMPs-related signature. RESULTS: A MMPs-related prognostic signature (including RNPEPL1, ADAM15, ADAM18, ADAMTS5, CAD, YME1L1, AMZ2, PSMD14, and COPS6) was identified. Using the median value, HCC patients in the high-risk group showed worse OS than those in the low-risk group. Immune microenvironment analysis showed that patients in the high-risk group had higher levels of M0 and M2 macrophages. Drug sensitivity analysis revealed that the IC50 values of sorafenib, cisplatin, and cytarabine were higher in the high-risk group. Finally, the single-cell cluster analysis results showed that YME1L1 and COPS6 were the major genes expressed in the monocyte cluster. CONCLUSIONS: A novel MMPs-related signature can be used to predict the prognosis of HCC. The findings of this research could potentially impact the predictability of the prognosis and treatment of HCC.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Matrix Metalloproteinases , Tumor Microenvironment , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/pathology , Humans , Liver Neoplasms/genetics , Liver Neoplasms/mortality , Liver Neoplasms/drug therapy , Liver Neoplasms/pathology , Prognosis , Matrix Metalloproteinases/metabolism , Matrix Metalloproteinases/genetics , Tumor Microenvironment/genetics , Gene Expression Regulation, Neoplastic , Biomarkers, Tumor/metabolism , Biomarkers, Tumor/genetics , Nomograms , Male , Gene Expression Profiling , Female , Transcriptome
11.
Opt Lett ; 49(5): 1225-1228, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38426979

ABSTRACT

Optical tweezer arrays (OTAs) have emerged as a powerful tool for quantum simulation, quantum computation, and quantum many-body physics. Conventional OTAs require bulky and costly optical components to generate multiple optical traps, such as spatial light modulators (SLMs). An integrated way to achieve on-chip OTAs is a sought-after goal for compact optical manipulation. In this Letter, we have numerically demonstrated compact on-chip multi-trap optical tweezers based on a guided wave-driven metalens. The presented on-chip optical tweezers are capable of capturing multiple polystyrene nanospheres in parallel. Moreover, we proposed an analytical design method to generate customized focal points from the integrated photonics chip into free space. Different trapping patterns are demonstrated to validate our proposed off-chip emission scheme. Our approach offers a promising solution to realize on-chip optical tweezers and provides a prospective way to realize elaborate emission control of guided waves into free-space beams.

12.
Appl Opt ; 63(7): 1867-1874, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38437291

ABSTRACT

Extreme ultraviolet (EUV) radiation plays a key role in the fields of material science, attosecond metrology, and lithography. However, the reflective optical components typically used in EUV systems contribute to their bulky size, weight, and increased costs for fabrication. In this paper, we theoretically investigate transmissive metalens designs capable of focusing the EUV light based on the Pancharatnam-Berry phase. The designed metalens is composed of nanoscale elliptical holes, which can guide and manipulate EUV light due to the higher refractive index of the vacuum holes compared to that of the surrounding material. We designed an EUV metalens with a diameter of 10 µm, which supports a focal length of 24 µm and a numerical aperture of up to 0.2. It can focus 55-nm EUV incident light to a diffraction-limited spot, and the focusing efficiency is calculated to be as high as about 7% over a broad EUV frequency range (50-65 nm). This study reveals the possibility of applying a dielectric metalens in the EUV region without a transmissive optical material.

13.
J Med Chem ; 67(4): 2802-2811, 2024 Feb 22.
Article in English | MEDLINE | ID: mdl-38330258

ABSTRACT

Chelerythrine chloride (CHE) is a quaternary benzo[c]phenanthridine alkaloid with an iminium group that was found to cause time- and concentration-dependent inhibition of CYP3A4. The loss of CYP3A4 activity was independent of NADPH. CYP3A4 competitive inhibitor ketoconazole and nucleophile N-acetylcysteine (NAC) slowed the inactivation. No recovery of CYP3A4 activity was observed after dialysis. Dihydrochelerythrine hardly inhibited CYP3A4, suggesting that the iminium group was primarily responsible for the inactivation. UV spectral analysis revealed that the maximal absorbance of CHE produced a significant red-shift after being mixed with NAC, suggesting that 1,2-addition possibly took place between the sulfhydryl group of NAC and iminium group of CHE. Molecular dynamics simulation and site-direct mutagenesis studies demonstrated that modification of Cys239 by the iminium group of CHE attributed to the inactivation. In conclusion, CHE is an affinity-labeling inactivator of CYP3A4. The observed enzyme inactivation resulted from the modification of Cys239 of CYP3A4 by the iminium group of CHE.


Subject(s)
Alkaloids , Antineoplastic Agents , Benzophenanthridines , Cytochrome P-450 CYP3A , Cytochrome P-450 CYP3A Inhibitors/pharmacology
14.
Chin J Traumatol ; 27(1): 11-17, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38052701

ABSTRACT

Tendinopathies are chronic diseases of an unknown etiology and associated with inflammation. Mesenchymal stem cells (MSCs) have emerged as a viable therapeutic option to combat the pathological progression of tendinopathies, not only because of their potential for multidirectional differentiation and self-renewal, but also their excellent immunomodulatory properties. The immunomodulatory effects of MSCs are increasingly being recognized as playing a crucial role in the treatment of tendinopathies, with MSCs being pivotal in regulating the inflammatory microenvironment by modulating the immune response, ultimately contributing to improved tissue repair. This review will discuss the current knowledge regarding the application of MSCs in tendinopathy treatments through the modulation of the immune response.


Subject(s)
Mesenchymal Stem Cells , Humans , Mesenchymal Stem Cells/physiology , Inflammation , Cell Differentiation
15.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1028794

ABSTRACT

Objective To explore the clinical application of the Shikani optical style(SOS)in guiding nasal tracheal intubation.Methods A retrospective analysis was made on clinical data of 60 patients who underwent selective operation under general anesthesia through nasal tracheal intubation from January 2017 to December 2022.According to the guidance methods of nasal tracheal intubation,the patients were divided into three groups with 20 cases in each group:video laryngoscope guided nasal tracheal intubation group(group V),fiberoptic bronchoscopy guided nasal tracheal intubation group(group F),and SOS guided nasal tracheal intubation group(group S).The grading of glottis exposure and epistaxis during tracheal intubation were recorded,as well as the success rate,completion time,and incidence of postoperative complications related to nasal tracheal intubation.Results The glottis exposure in the group F and group S were both grade Ⅰ.Among the group V,there were 7 cases of gradeⅠ,10 cases of gradeⅡ,and 3 cases of grade Ⅲ.The glottis exposure effect of patients in the group F and S was significantly better than that of the group V(Z =-4.274,P = 0.000;Z =-4.274,P = 0.000).There were 15 and 14 patients in the group F and the group S without epistaxis,and 5 and 6 patients with mild epistaxis,respectively.There were no patients with severe epistaxis in the group F and the group S.In the group V,there were 7 patients without epistaxis,10 patients with mild epistaxis,and 3 patients with severe epistaxis.The degree of epistaxis in the group F and the group S was significantly less than that in the group V(Z =-2.678,P =0.007;Z =-2.402,P =0.016).The median time for tracheal intubation in the group S was 37.5(34.3,41.5)s,significantly shorter than 45.0(39.8,72.5)s in the group V and 89.0(76.0,102.5)s in the group F(Z =15.703,P =0.013;Z =32.050,P =0.000),with the group V being significantly shorter than the group F(Z =-16.347,P =0.009).The nasal tracheal intubation failed in 2 cases in the group V,while was all successfully completed in the group F and the group S.The difference of success rate was not statistically significant among the three groups(P>0.05).There were no statistically significant differences in the rates of postoperative nasopharyngeal pain and nasal congestion among the three groups(P>0.05).Conclusion The method of SOS-guided nasal tracheal intubation can provide good glottis exposure and achieve a satisfactory success rate of tracheal intubation without increasing the risk of adverse reactions,which can be regarded as a safe and effective method of nasal tracheal intubation.

16.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1028804

ABSTRACT

Objective To explore the safety and feasibility of single-segment paravertebral nerve block(PVNB)in elderly patients undergoing inguinal hernioplasty.Methods A retrospective analysis was made on clinical data of 58 elderly patients who underwent open tension-free inguinal hernioplasty from January 2016 to December 2022.According to the anesthesia method,they were divided into two groups with 29 cases in each:single-segment PVNB group(P group)and single subarachnoid block group(S group).Patients in the P group were given L1 single-segment PVNB guided by ultrasound combined with peripheral nerve stimulators or simple peripheral nerve stimulators by using 0.4%ropivacaine 20 ml.Patients in the S group underwent puncture in the interspinous space between L3/4 and received 0.5%bupivacaine 10 mg.The mean arterial pressure and heart rate before anesthesia(T0),at the time of skin incision(T1),at the time of hernia sac dissection(T2),and at the time of wound closure(T3)were recorded,and the block levels,anesthetic effect,remedial rate of fentanyl,local anesthetic toxicity,peripheral nerve injury,urinary retention,delirium,and nausea and vomiting of the patients were recorded.The patient's satisfaction with anesthesia was followed up.Results All the 58 patients underwent surgery smoothly.The difference in block levels was statistically significant between the two groups of patients(Z =-4.144,P =0.000),while the differences in the remedial rate of fentanyl,anesthesia effect,and anesthesia satisfaction were not statistically significant(χ2 =0.269,P =0.604;Z =-1.430,P =0.153;Z =-1.395,P =0.163).There were no statistically significant differences in mean arterial pressure and heart rate changes between the two groups at different time points(F =0.002,P = 0.960;F =0.260,P =0.612).The rate of urinary retention in the P group was significantly lower than that in the S group(0.0%vs.24.1%,Fisher's test,P =0.010).There were no statistically significant differences in rates of dilirium and nausea and vomitting(P>0.05).All the patients did not experience local anesthetic toxicity or peripheral nerve injury during the perioperative period.Conclusion Single-segment PVNB can provide comprehensive anesthesia and analgesia for elderly patients undergoing inguinal hernioplasty,helping to maintain the stability of intraoperative hemodynamics and reducing the risk of postoperative adverse reactions.

17.
Drug Metab Dispos ; 52(3): 188-197, 2024 Feb 14.
Article in English | MEDLINE | ID: mdl-38123940

ABSTRACT

Dihydrotanshinone I (DHTI) is a pharmacologically active component occurring in the roots of the herbal medicine Salvia miltiorrhiza Bunge. This study investigated DHTI-induced inhibition of CYP1A1, CYP1A2, and CYP1B1 with the aim to determine the potential effects of DHTI on the bioactivation of estradiol (E2), possibly related to preventive/therapeutic strategy for E2-associated breast cancer. Ethoxyresorufin as a specific substrate for CYP1s was incubated with human recombinant CYP1A1, CYP1A2, or CYP1B1 in the presence of DHTI at various concentrations. Enzymatic inhibition and kinetic behaviors were examined by monitoring the formation of the corresponding product. Molecular docking was further conducted to define the interactions between DHTI and the three CYP1s. The same method and procedure were employed to examine the DHTI-induced alteration of E2 metabolism. DHTI showed significant inhibition of ethoxyresorufin O-deethylation activity catalyzed by CYP1A1, CYP1A2 and CYP1B1 in a concentration-dependent manner (IC50 = 0.56, 0.44, and 0.11 µM, respectively). Kinetic analysis showed that DHTI acted as a competitive type of inhibitor of CYP1A1 and CYP1B1, whereas it noncompetitively inhibited CYP1A2. The observed enzyme inhibition was independent of NADPH and time. Molecular docking analysis revealed hydrogen bonding interactions between DHTI and Asp-326 of CYP1B1. Moreover, DHTI displayed preferential activity to inhibit 4-hydroxylation of E2 (a genotoxic pathway) mediated by CYP1B1. Exposure to DHTI could reduce the risk of genotoxicity induced by E2. SIGNIFICANCE STATEMENT: CYP1A1, CYP1A2, and CYP1B1 enzymes are involved in the conversion of estradiol (E2) into 2-hydroxyestradiol (2-OHE2) and 4-hydroxyestradiol (4-OHE2) through oxidation. 2-OHE2 is negatively correlated with breast cancer risk, and 4-OHE2 may be a significant initiator and promoter of breast cancer. The present study revealed that dihydrotanshinone I (DHTI) competitively inhibits CYP1A1/CYP1B1 and noncompetitively inhibits CYP1A2. DHTI exhibits a preference for inhibiting the genotoxicity associated with E2 4-hydroxylation pathway mediated by CYP1B1, potentially reducing the risk of 4-OHE2-induced genotoxicity.


Subject(s)
Breast Neoplasms , Cytochrome P-450 CYP1A2 , Furans , Phenanthrenes , Quinones , Humans , Female , Cytochrome P-450 CYP1A2/metabolism , Cytochrome P-450 CYP1A1/metabolism , Molecular Docking Simulation , Kinetics , Cytochrome P-450 CYP1B1/metabolism , Estradiol/pharmacology , Estradiol/metabolism
18.
Commun Biol ; 6(1): 1243, 2023 12 08.
Article in English | MEDLINE | ID: mdl-38066175

ABSTRACT

Protein post-translational modifications (PTMs) with various acyl groups play central roles in Streptomyces. But whether these acyl groups can be further modified, and the influences of these potential modifications on bacterial physiology have not been addressed. Here in Streptomyces roseosporus with rich crotonylation, a luciferase monooxygenase LimB is identified to elaborately regulate the crotonylation level, morphological development and antibiotic production by oxidation on the crotonyl groups of an acetyl-CoA synthetase Acs. This chemical modification on crotonylation leads to Acs degradation via the protease ClpP1/2 pathway and lowered intracellular crotonyl-CoA pool. Thus, we show that acyl groups after PTMs can be further modified, herein named post-PTM modification (PPM), and LimB is a PTM modifier to control the substrate protein turnover for cell development of Streptomyces. These findings expand our understanding of the complexity of chemical modifications on proteins for physiological regulation, and also suggest that PPM would be widespread.


Subject(s)
Ligases , Streptomyces , Acetyl Coenzyme A , Mixed Function Oxygenases , Proteins
19.
Nat Prod Res ; : 1-10, 2023 Dec 06.
Article in English | MEDLINE | ID: mdl-38054801

ABSTRACT

Phytochemical analysis of the fruits of Cyclocodon lancifolius led to the isolation of two new phenylpropanoid-derived glycosides (1-2), two new geranyl glucosides (3-4), and nine known compounds (5-13). Their chemical structures were elucidated by extensive spectroscopic data. The absolute configuration of the sugar moiety was determined by hydrolysis and derivatization. All compounds were evaluated for their xanthine oxidase (XO) and α-glucosidase inhibitory activities, and four compounds showed weak inhibitory activity towards XO.

20.
World J Gastroenterol ; 29(44): 5894-5906, 2023 Nov 28.
Article in English | MEDLINE | ID: mdl-38111507

ABSTRACT

BACKGROUND: Donor-recipient size mismatch (DRSM) is considered a crucial factor for poor outcomes in liver transplantation (LT) because of complications, such as massive intraoperative blood loss (IBL) and early allograft dysfunction (EAD). Liver volumetry is performed routinely in living donor LT, but rarely in deceased donor LT (DDLT), which amplifies the adverse effects of DRSM in DDLT. Due to the various shortcomings of traditional manual liver volumetry and formula methods, a feasible model based on intelligent/interactive qualitative and quantitative analysis-three-dimensional (IQQA-3D) for estimating the degree of DRSM is needed. AIM: To identify benefits of IQQA-3D liver volumetry in DDLT and establish an estimation model to guide perioperative management. METHODS: We retrospectively determined the accuracy of IQQA-3D liver volumetry for standard total liver volume (TLV) (sTLV) and established an estimation TLV (eTLV) index (eTLVi) model. Receiver operating characteristic (ROC) curves were drawn to detect the optimal cut-off values for predicting massive IBL and EAD in DDLT using donor sTLV to recipient sTLV (called sTLVi). The factors influencing the occurrence of massive IBL and EAD were explored through logistic regression analysis. Finally, the eTLVi model was compared with the sTLVi model through the ROC curve for verification. RESULTS: A total of 133 patients were included in the analysis. The Changzheng formula was accurate for calculating donor sTLV (P = 0.083) but not for recipient sTLV (P = 0.036). Recipient eTLV calculated using IQQA-3D highly matched with recipient sTLV (P = 0.221). Alcoholic liver disease, gastrointestinal bleeding, and sTLVi > 1.24 were independent risk factors for massive IBL, and drug-induced liver failure was an independent protective factor for massive IBL. Male donor-female recipient combination, model for end-stage liver disease score, sTLVi ≤ 0.85, and sTLVi ≥ 1.32 were independent risk factors for EAD, and viral hepatitis was an independent protective factor for EAD. The overall survival of patients in the 0.85 < sTLVi < 1.32 group was better compared to the sTLVi ≤ 0.85 group and sTLVi ≥ 1.32 group (P < 0.001). There was no statistically significant difference in the area under the curve of the sTLVi model and IQQA-3D eTLVi model in the detection of massive IBL and EAD (all P > 0.05). CONCLUSION: IQQA-3D eTLVi model has high accuracy in predicting massive IBL and EAD in DDLT. We should follow the guidance of the IQQA-3D eTLVi model in perioperative management.


Subject(s)
End Stage Liver Disease , Liver Transplantation , Humans , Male , Female , Liver Transplantation/adverse effects , Living Donors , Retrospective Studies , End Stage Liver Disease/diagnosis , End Stage Liver Disease/surgery , End Stage Liver Disease/etiology , Severity of Illness Index , Risk Factors , Graft Survival
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