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1.
Nat Commun ; 15(1): 5628, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38965215

ABSTRACT

The control of a molecule's geometry, chirality, and physical properties has long been a challenging pursuit. Our study introduces a dependable method for assembling D3-symmetric trigonal bipyramidal coordination cages. Specifically, D2h-symmetric anions, like oxalate and chloranilic anions, self-organize around a metal ion to form chiral-at-metal anionic complexes, which template the formation of D3-symmetric trigonal bipyramidal coordination cages. The chirality of the trigonal bipyramid is determined by the point chirality of chiral amines used in forming the ligands. Additionally, these cages exhibit chiral selectivity for the included chiral-at-metal anionic template. Our method is broadly applicable to various ligand systems, enabling the construction of larger cages when larger D2h-symmetric anions, like chloranilic anions, are employed. Furthermore, we successfully produce enantiopure trigonal bipyramidal cages with anthracene-containing backbones using this approach, which would be otherwise infeasible. These cages exhibit circularly polarized luminescence, which is modulable through the reversible photo-oxygenation of the anthracenes.

2.
Nat Prod Res ; : 1-8, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38962949

ABSTRACT

The phytochemical investigation on the rhizomes of Paris yunnanensis Franch. resulted in the discovery and characterisation of six compounds, including two new saponins named parisyunnanosides M-N (1-2), and four known ones (3-6). The structures of isolated compounds were determined by spectroscopic data analysis and chemical methods. Compound 2 is a pregnane-type saponin with a special α,ß-unsaturated carboxylic acid moiety at C-17, which is first discovered in genus Paris. The anti-inflammatory activity of the isolated compounds was assessed in vitro. The results demonstrated that compounds 3 and 4 could significantly inhibit the production of NO which was induced by LPS in RAW 264.7 cells with IC50 values of 0.67 ± 0.17 µM and 0.85 ± 0.12 µM, respectively.

3.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 46(3): 324-328, 2024 Jun.
Article in Chinese | MEDLINE | ID: mdl-38953255

ABSTRACT

Objective To assess the influences of self-and interviewer-administered methods on the scores of anxiety and depression questionnaires among the patients with sports injuries.Methods A total of 532 participants with sports injuries treated in the Sports Medicine Center of West China Hospital,Sichuan University from November 2022 to May 2023 were included.They were randomly assigned to either the interviewer-administered group (n=270) or the self-administered group (n=262) to complete the generalized anxiety disorder (GAD-7) and the patient health questionnaire (PHQ-9) scales.The total scores and prevalence rates of anxiety and depression were compared between the two groups.Results There was no statistically significant difference in gender,occupation,or surgical site between the two groups (all P>0.05).The self-administered group had higher scores of GAD-7 and PHQ-9 scales than the interviewer-administered group (P<0.001,P<0.001).A greater proportion of participants in the self-administered group than in the interview-administered group met the criteria for mild to moderate anxiety and depression (P<0.001,P=0.002).The prevalence rates of moderate to severe anxiety (GAD-7≥10) and depression (PHQ-9≥10) showed no statistically significant difference between the two groups (P=0.761,P=0.086).Conclusion This study demonstrates that the participants in the self-administered group are more likely to report mild to moderate symptoms of anxiety and depression than those in the interviewer-administered group.


Subject(s)
Anxiety , Depression , Humans , Surveys and Questionnaires , Depression/epidemiology , Depression/diagnosis , Female , Anxiety/epidemiology , Male , Adult , Athletic Injuries/psychology , Athletic Injuries/epidemiology , China/epidemiology , Middle Aged , Young Adult
4.
Cardiology ; 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38964309

ABSTRACT

INTRODUCTION: To investigate the expression and predictive value of NOD-like receptor thermoprotein domain-related protein 3 (NLRP3) in patients with nonvalvular atrial fibrillation (NVAF) with ejection fraction preserved heart failure (HFpEF). METHODS: A retrospective analysis of 121 patients diagnosed with NVAF. According to the occurrence of HFpEF, 81 patients was assigned in the NVAF group and 40 patients in the NVAF/HFpEF group. The levels of NLRP3, B natriuretic peptide (BNP), and interleukin-1ß were determined using enzyme-linked immunosorbent assay (ELISA). Independent predictors for HFpEF in NVAF was determined using logistic regression. The receiver operating characteristic curve (ROC) was used to evaluate the predictive value of each factor. RESULTS: Expression levels of NLRP3, BNP, and IL-1ß in the NVAF/HFpEF group, as well as the H2FPEF score was significantly higher than those in the NVAF group. Pearson analysis showed that NLRP3, BNP, and IL-1ß expression levels in NVAF patients and H2FPEF score was positively correlated (r=0.409, r=0.244, r=0.299, p < 0.001). Multivariate logistic regression analysis showed that NLRP3, BNP, or H2FPEF score can be used as independent factor for predicting the occurrence of HFpEF in NVAF. ROC curves showed that the area under the curve (AUC) of NLRP3, BNP, and H2FPEF score for predicting the occurrence of HFpEF in NVAF patients were 0.856, 0.831 and 0.811, respectively. CONCLUSION: NLRP3 level is elevated in the peripheral blood of NVAF patients with HFpEF and is positively correlated with the H2FPEF score. NLRP3 may serve as a potential predictor of HFpEF in patients with NVAF.

5.
Int Ophthalmol ; 44(1): 315, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38967725

ABSTRACT

Acute acquired comitant esotropia (AACE) is mainly characterized by sudden onset, accompanied by diplopia, without extraocular muscles paralysis or ocular motility disorders. In recent years, the incidence of AACE has been increasing, researchers have found that this phenomenon may be related to the widespread use of electronic devices and the increase in the number of people working from home during the COVID-19 pandemic. However, its neural mechanisms have not been fully elucidated. This article primarily reviews the latest developments in the diagnosis and treatment of AACE from the perspectives of etiology and treatment methods, aiming to provide direction for future in-depth exploration of the pathogenesis and treatment approaches of this disease.


Subject(s)
COVID-19 , Esotropia , Humans , Esotropia/diagnosis , Esotropia/therapy , Esotropia/physiopathology , Esotropia/etiology , COVID-19/complications , COVID-19/diagnosis , COVID-19/epidemiology , Acute Disease , Oculomotor Muscles/physiopathology , SARS-CoV-2
6.
BMC Womens Health ; 24(1): 385, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38961427

ABSTRACT

BACKGROUND: In this study, we investigated the relationship between the risk of postoperative progressive disease (PD) in breast cancer and depression and sleep disorders in order to develop and validate a suitable risk prevention model. METHODS: A total of 750 postoperative patients with breast cancer were selected from the First People's Hospital of LianYunGang, and the indices of two groups (an event group and a non-event group) were compared to develop and validate a risk prediction model. The relationship between depression, sleep disorders, and PD events was investigated using the follow-up data of the 750 patients. RESULTS: SAS, SDS, and AIS scores differed in the group of patients who experienced postoperative disease progression versus those who did not; the differences were statistically significant and the ability to differentiate prognosis was high. The area under the receiver operating characteristic (ROC) curves (AUC) were: 0.8049 (0.7685-0.8613), 0.768 (0.727-0.809), and 0.7661 (0.724--0.808), with cut-off values of 43.5, 48.5, and 4.5, respectively. Significant variables were screened by single-factor analysis and multi-factor analysis to create model 1, by lasso regression and cross-lasso regression analysis to create model 2, by random forest calculation method to create model 3, by stepwise regression method (backward method) to create model 4, and by including all variables for Cox regression to include significant variables to create model 5. The AUC of model 2 was 0.883 (0.848-0.918) and 0.937 (0.893-0.981) in the training set and validation set, respectively. The clinical efficacy of the model was evaluated using decision curve analysis and clinical impact curve, and then the model 2 variables were transformed into scores, which were validated in two datasets, the training and validation sets, with AUCs of 0.884 (0.848-0.919) and 0.885 (0.818-0.951), respectively. CONCLUSION: We established and verified a model including SAS, SDS and AIS to predict the prognosis of breast cancer patients, and simplified it by scoring, making it convenient for clinical use, providing a theoretical basis for precise intervention in these patients. However, further research is needed to verify the generalization ability of our model.


Subject(s)
Breast Neoplasms , Depression , Disease Progression , Nomograms , Sleep Wake Disorders , Humans , Breast Neoplasms/complications , Female , Sleep Wake Disorders/epidemiology , Middle Aged , Adult , Depression/epidemiology , Aged , Risk Factors , ROC Curve , Risk Assessment/methods , Prognosis
7.
Chin Med Sci J ; 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38915216

ABSTRACT

Peking Union Medical College (PUMC) launched the "4+4" Clinical Medicine Pilot Class in 2018, admitting students with non-medical backgrounds from top universities, aligning with national medical talent training policies to foster diverse and eager learners in medicine. On the occasion of the graduation of the first class of the "4+4" clinical medical pilot program at PUMC in 2023, we reviewed the teaching reform in the pilot program and carried out a systematic survey and interviews with students, faculties, and management staff of the pilot class. This article reports on the measures taken by the pilot class at PUMC in enrollment and curriculum setting, and demonstrates the achievements of the pilot class in terms of student academic background structure, knowledge acquisition and skill learning, scientific research ability, and course evaluation. The results indicated that the pilot class had met the national demand for the "medicine + x" talent training model. More specifically, with a diverse academic backgrounds, the pilot class graduates had academic levels comparable to the eight-year medical education graduates, and their scientific research abilities were satisfactory. The pilot program at PUMC will optimize the curriculum setting, strengthen the construction of faculty, learning resources, and teaching facilities, reform the academic evaluation methods, thus deepening the reform of medical education and improving the "4+4" MD program as a novel medical education model.

8.
Sensors (Basel) ; 24(11)2024 May 30.
Article in English | MEDLINE | ID: mdl-38894314

ABSTRACT

BACKGROUND: Previous investigations have shown a positive relationship between baseball pitching velocity and the kinetic chain involved in pitching motion. However, no study has examined the influence of finger characteristics on pitching velocity and rate of spin via a sensor-embedded baseball. METHODS: Twenty-one pitchers volunteered and were recruited for this study. An experimental baseball embedded with a force sensor and an inertial measurement unit was designed for pitching performance measurement. Finger length and strength were measured as dependent variables. Spin rate and velocity were independent variables. Pearson product-moment correlations (r) and intraclass correlation coefficients (ICCs) determined the relationship between finger characteristics and pitching performance. RESULTS: Finger length discrepancy, two-point pinch strength, index finger RFD (rate of force development), middle finger impulse, and force discrepancy had significant correlations with spin rate (r = 0.500~0.576, p ≤ 0.05). Finger length discrepancy, two-point pinch, three-point pinch strength, index and middle finger RFD, middle finger impulse, and force combination had significant correlations with fastball pitching velocity (r = 0.491~0.584, p ≤ 0.05). CONCLUSIONS: Finger length discrepancy, finger pinch strength, and pitching finger force including maximal force and RFD may be factors that impact fastball spin rate and fastball pitching velocity.


Subject(s)
Baseball , Fingers , Baseball/physiology , Humans , Fingers/physiology , Male , Biomechanical Phenomena/physiology , Young Adult , Adult , Athletic Performance/physiology
9.
Phytomedicine ; 132: 155819, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38885579

ABSTRACT

BACKGROUND: Dysfunction of dopamine homeostasis (DAH), which is regulated by vesicular monoamine transporter 2 (VMAT2), is a vital cause of dopamine (DA) neurotoxicity and motor deficits in Parkinson's disease (PD). Gastrodin (4-hydroxybenzyl alcohol 4-O-ß-D-glucoside; GTD), a natural active compound derived from Gastrodia elata Blume, can be used to treat multiple neurological disorders, including PD. However, whether GTD regulates VMAT2-mediated DAH dysfunction in PD models remains unclear. PURPOSE: To explore whether GTD confers dopaminergic neuroprotection by facilitating DA vesicle storage and maintaining DAH in PD models. METHODS: Mice were treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and PC12 cells with 1-methyl-4-phenyl-pyridinium (MPP+) to induce PD characteristics. Multiple behavioural tests were performed to evaluate the motor functions of the mice. HPLC was used to measure DA and 3,4-dihydroxyphenylacetic acid (DOPAC) levels. Transmission electron microscopy was used to observe synaptic vesicles. Molecular docking and molecular dynamics were used to determine the binding affinity of GTD to the target protein. Reserpine (Res, a VMAT2 inhibitor) and PD0325901 (901, a MEK inhibitor) were employed to investigate the mechanism of GTD. Western blotting and immunohistochemistry were used to assess the expression of the target proteins. RESULTS: GTD attenuated motor deficits and dopaminergic neuronal injury, reversed the imbalance of DAH, and increased VMAT2 levels and vesicle volume in MPTP-induced mice. GTD ameliorated cell damage, ROS release, and dysfunction of DAH in MPP+-induced PC12 cells. Moreover, the neuroprotective effects of GTD were reversed by Res in vitro and in vivo. Furthermore, GTD can activate the MEK/ERK/CREB pathway to upregulate VMAT2 in vitro and in vivo. Interestingly, 901 reversed the effects of GTD on VMAT2 and dopaminergic neuronal impairment. CONCLUSION: GTD relieved PD-related motor deficits and dopaminergic neuronal impairment by facilitating MEK-depended VMAT2 to regulate DAH, which offers new insights into its therapeutic potential.

10.
Ying Yong Sheng Tai Xue Bao ; 35(5): 1177-1186, 2024 May.
Article in Chinese | MEDLINE | ID: mdl-38886415

ABSTRACT

The radial growth of trees in alpine timberline is particularly sensitive to climate change. We sampled and disposed tree-ring cores of three coniferous tree species including Juniperus saltuaria, Abies forrestii, and Larix potaninii at alpine timberline in Yading Nature Reserve. The standard tree-ring chronology was used to explore the response of radial growth of different timberline species to climate change. The results showed that radial growth of L. potaninii increased after 2000, while that of A. forrestii declined after 2002, and J. saltuaria showed a significant decreasing growth trend in the past 10 years. Such results indicated divergent growth responses to climate factors among the three tree species at alpine timberline. The radial growth of J. saltuaria was sensitive to temperature, and was positively correlated with the minimum temperature from previous October to current August, the mean tempera-ture from previous November to current April and from current July to October, but was negatively associated with the relative humidity from current July to October. The radial growth of A. forrestii showed negative correlation with mean temperature and the maximum temperature from May to June in the current year, while it exhibited positive association with the relative humidity and the Palmer drought severity index from May to June in the current year. L. potaninii radial growth was positively associated with mean temperature and the maximum temperature of November-December in the previous year, the maximum temperature of current March and mean temperature of current August. The temporal stability of climate-growth relationship varied among different timberline species. The positive correlation between radial growth of A. forrestii and J. saltuaria and temperature gradually decreased, while the posi-tive relationship of L. potaninii radial growth and temperature gradually increased. Under the background of climate warming, rapid rise in surface air temperatures may promote the radial growth of L. potaninii, while inhibit that of J. saltuaria and A. forrestii, which may change the position of regional timberline.


Subject(s)
Climate Change , Larix , China , Larix/growth & development , Juniperus/growth & development , Abies/growth & development , Ecosystem , Trees/growth & development , Conservation of Natural Resources , Temperature , Plant Stems/growth & development , Altitude
11.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(3): 911-919, 2024 Jun.
Article in Chinese | MEDLINE | ID: mdl-38926988

ABSTRACT

OBJECTIVE: To screen interleukin (IL)-1ß secretion-related membrane transporters by macrophage experiment in vitro and conventional knockout mice. METHODS: THP-1 cell line was differentiated to obtain human THP-1-derived macrophages, and the primary macrophages were obtained from human peripheral blood. FVB wild-type mice with the same sex and age were used as the controls of MRP1 knockout mice. The macrophages in abdominal cavity and bone marrow of mice were cultivated. The cells were treated with ABCC1/MRP1, ABCG2/BCRP, ABCB1/P-gp, OATP1B1, and MATE transporter inhibitors, then stimulated by lipopolysaccharide and adenosine triphosphate. The secretion level of IL-1ß was detected by ELISA, Western blot, and immunofluorescence. RESULTS: After inhibiting ABCC1/MRP1 transporter, the secretion of IL-1ß decreased significantly, while inhibition of the other 4 transporters had no effect. In animal experiment, the level of IL-1ß secreted by macrophages in bone marrow of MRP1 knockout mice was significantly lower than control group (P < 0.05). CONCLUSION: ABCC1/MRP1 transporter is a newly discovered IL-1ß secretion pathway, which is expected to become a new target for solving clinical problems such as cytokine release syndrome.


Subject(s)
Down-Regulation , Interleukin-1beta , Macrophages , Mice, Knockout , Multidrug Resistance-Associated Proteins , Interleukin-1beta/metabolism , Mice , Animals , Humans , Multidrug Resistance-Associated Proteins/metabolism , Macrophages/metabolism , THP-1 Cells , Lipopolysaccharides
12.
Dev Psychobiol ; 66(6): e22519, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38922899

ABSTRACT

Although neighborhood contexts serve as upstream determinants of health, it remains unclear how these contexts "get under the skin" of Mexican-origin youth, who are disproportionately concentrated in highly disadvantaged yet co-ethnic neighborhoods. The current study examines the associations between household and neighborhood socioeconomic status (SES), neighborhood racial-ethnic and immigrant composition, and hair cortisol concentration (HCC)-a physiological index of chronic stress response-among Mexican-origin adolescents from low-income immigrant families in the United States. A total of 297 (54.20% female; mage = 17.61, SD = 0.93) Mexican-origin adolescents had their hair cortisol collected, and their residential addresses were geocoded and merged with the American Community Survey. Neighborhoods with higher Hispanic-origin and foreign-born residents were associated with higher neighborhood disadvantage, whereas neighborhoods with higher non-Hispanic White and domestic-born residents were associated with higher neighborhood affluence. Mexican-origin adolescents living in neighborhoods with a higher proportion of Hispanic-origin residents showed lower levels of HCC, consistent with the role of the ethnic enclave. In contrast, adolescents living in more affluent neighborhoods showed higher levels of HCC, possibly reflecting a physiological toll. No association was found between household SES and HCC. Our findings underscore the importance of taking sociocultural contexts and person-environment fit into consideration when understanding how neighborhoods influence adolescents' stress physiology.


Subject(s)
Emigrants and Immigrants , Hair , Hydrocortisone , Mexican Americans , Poverty , Humans , Adolescent , Female , Male , Hydrocortisone/metabolism , Hair/chemistry , United States/ethnology , Poverty/ethnology , Residence Characteristics , Neighborhood Characteristics , Social Class , Stress, Psychological/metabolism , Stress, Psychological/ethnology
13.
Plant Physiol Biochem ; 212: 108778, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38838570

ABSTRACT

The albino tea cultivar is one of the most important germplasms for key gene mining and high-quality tea producing. In order to elucidate the chlorophyll-deficient mechanism of albino cultivar 'Huangjinya' and its offspring, color difference, photosynthetic pigments and the relevant genes' expression of the tender shoots were comprehensively investigated in this study. Among the tested 16 offspring, 5 exhibited albino phenotype in spring and autumn, 3 showed albino phenotype in spring but normal green in autumn, while the rests were all normal green. The shoot of albino offspring had significantly higher lightness and/or yellowness than that of green ones, and possessed dramatically lower photosynthetic pigments and chlorophyll precursor protochlorophyllide (Pchlide), as well as higher chlorophyll a/chlorophyll b but lower chlorophylls/carotenoids in comparison with green ones. Among the tested genes involved in chlorophyll and carotenoid metabolism pathways, expression of the magnesium protoporphyrin IX monomethyl ester cyclase (CRD), 3,8-divinyl chlorophyllide 8-vinyl reductase (DVR), 5-aminolevulinate dehydratase 1 (HEMB1), 1-deoxy-D-xylulose 5-phosphate synthase 1 (DXS1) and 4-hydroxy-3-methylbut-2-enyl diphosphate reductase (ISPH) was remarkably down-regulated in shoots of the albino offspring. Color difference indices of the offspring were significantly correlated with the levels of photosynthetic pigments and Pchlide, and low level of chlorophylls in shoot of albino offspring was mainly due to conversion obstacle from magnesium protoporphyrin Ⅸ (Mg-Proto IX) to Pchlide which might be attributed to down-regulatory expression of CRD and DVR.


Subject(s)
Chlorophyll , Phenotype , Protochlorophyllide , Protoporphyrins , Chlorophyll/metabolism , Protochlorophyllide/metabolism , Protoporphyrins/metabolism , Gene Expression Regulation, Plant , Plant Proteins/metabolism , Plant Proteins/genetics , Photosynthesis
14.
Ren Fail ; 46(2): 2369695, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38938162

ABSTRACT

BACKGROUND: This study aims to establish a simplified and effective animal model of catheter malfunction caused by omental wrapped using negative pressure suction. METHOD: The peritoneal dialysis catheter outlet was linked to a negative-pressure (0-75mmHg) suction pump to intensify the negative pressure. Different negative pressures were tested for model construction in vitro. In vivo, a model of peritoneal catheter malfunction caused by omental wrapped was constructed in five beagles after catheter placement. Catheter drainage conditions and related complications were monitored before and after the model establishment. RESULTS: In the vitro experiment, the overall success rate of constructed models was 90% (36/40). The total malfunction rate was higher in 62.5 mmHg (10/10) and 75 mmHg (10/10) than in 12.5 mmHg (8/10) and 37.5 mmHg (8/10). The outflow velocity of dialysate at 62.5 mmHg was significantly lower than that at 12.5 mmHg and 37.5 mmHg, without a statistically significant difference compared to 75 mmHg. In the in vivo experiment, catheter outflow velocity increased, and residual fluid volume decreased after omental wrapped (99.6 ± 6.7 ml/min vs. 32.6 ± 4.6 ml/min at initial five minutes, p < 0.0001; 69.2 ± 16.3 ml vs. 581.0 ± 109.4 ml, p < 0.001). And the outflow velocity was finally below 2 ml/min. No severe related complications (such as infection, organ damage, or bleeding) were observed through laparoscopic examination and dialysate tests seven days post-operation. CONCLUSION: Utilizing negative pressure suction to increase negative pressure around catheter tip is a simple, safe, and effective method for establishing an animal model of omental wrapped leading to catheter malfunction.


Subject(s)
Equipment Failure , Omentum , Peritoneal Dialysis , Animals , Dogs , Suction/instrumentation , Peritoneal Dialysis/instrumentation , Peritoneal Dialysis/adverse effects , Catheters, Indwelling/adverse effects , Disease Models, Animal , Male , Models, Animal
15.
J Org Chem ; 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38940722

ABSTRACT

Herein, a photocatalytic umpolung strategy for reductive carboxylation of imines for the synthesis of α-amino acids was disclosed. Carbon dioxide radical anion (CO2•-) generated from formate is the key single electron reductant in the reactions. An unprecedentedly broad substrate scope of imines with excellent reaction yields was obtained with carbon dioxide (CO2) and formate salt as carbon sources.

16.
Int Immunopharmacol ; 138: 112547, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38943969

ABSTRACT

Non-small cell lung cancer (NSCLC) accounts for more than 80% of lung cancer cases, and the 5-year survival rate of patients remains unsatisfactory. MicroRNAs (miRNAs) are small endogenous noncoding RNAs that are considered essential posttranscriptional regulators of tumorigenesis, including NSCLC. In this study, we aimed to investigate the biological role of miR-3074-5p in NSCLC cells and the underlying molecular mechanisms. We showed that miR-3074-5p expression was decreased in human NSCLC specimens and cell lines. Moreover, miR-3074-5p overexpression inhibited cell proliferation, migration and invasion and induced apoptosis and cell cycle arrest. In addition, miR-3074-5p overexpression not only suppressed tumor growth but also enhanced the antitumor effect of paclitaxel (PTX) on NSCLC cells in vitro and in vivo. A transcriptome sequencing assay revealed genes that were differentially expressed after miR-3074-5p overexpression, and among the genes whose expression levels were most significantly decreased, tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ) was a target of miR-3074-5p. The regulatory effect of miR-3074-5p on YWHAZ expression was verified by Western blotting and dual-luciferase reporter assays. The inhibition of A549 cell growth, migration and invasion was reversed by YWHAZ overexpression. Furthermore, we showed that PTX stimulated the expression of the YWHAZ and Hsp27 proteins and promoted the phosphorylation of Hsp27 (at S15 and S78). YWHAZ was confirmed to interact with Hsp27 in A549 cells, and downregulating YWHAZ expression promoted the degradation of the Hsp27 protein. Taken together, these results suggest that the miR-3074-5p/YWHAZ/Hsp27 axis may be a novel therapeutic target for NSCLC treatment.

17.
Front Oncol ; 14: 1358947, 2024.
Article in English | MEDLINE | ID: mdl-38903718

ABSTRACT

Objective: To develop a CT-based nomogram to predict the response of advanced esophageal squamous cell carcinoma (ESCC) to neoadjuvant chemotherapy plus immunotherapy. Methods: In this retrospective study, 158 consecutive patients with advanced ESCC receiving contrast-enhanced CT before neoadjuvant chemotherapy plus immunotherapy were randomized to a training cohort (TC, n = 121) and a validation cohort (VC, n = 37). Response to treatment was assessed with response evaluation criteria in solid tumors. Patients in the TC were divided into the responder (n = 69) and non-responder (n = 52) groups. For the TC, univariate analyses were performed to confirm factors associated with response prediction, and binary analyses were performed to identify independent variables to develop a nomogram. In both the TC and VC, the nomogram performance was assessed by area under the receiver operating characteristic curve (AUC), calibration slope, and decision curve analysis (DCA). Results: In the TC, univariate analysis showed that cT stage, cN stage, gross tumor volume, gross volume of all enlarged lymph nodes, and tumor length were associated with the response (all P < 0.05). Binary analysis demonstrated that cT stage, cN stage, and tumor length were independent predictors. The independent factors were imported into the R software to construct a nomogram, showing the discriminatory ability with an AUC of 0.813 (95% confidence interval: 0.735-0.890), and the calibration curve and DCA showed that the predictive ability of the nomogram was in good agreement with the actual observation. Conclusion: This study provides an accurate nomogram to predict the response of advanced ESCC to neoadjuvant chemotherapy plus immunotherapy.

18.
Behav Med ; : 1-12, 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38874131

ABSTRACT

Mexican-origin youth, as a large and growing population among U.S. youth, have been disproportionately affected by COVID-19. Understanding what, when, and how sociocultural factors may influence their COVID-19 vaccine uptake could inform current and future pandemic-response interventions promoting vaccination behaviors among Mexican-origin youth. The current study takes a developmental approach to reveal the long-term and short-term sociocultural antecedents of 198 Mexican-origin adolescents' COVID-19 vaccination uptake behaviors and explores the underlying mechanism of these associations based on the Knowledge-Attitude-Behavior model. The current study adopted Wave 1 (2012-2015) and Wave 4 (2021-2022) self-reported data from a larger study. Analyses were conducted to examine four mediation models for four sociocultural antecedents-daily discrimination, ethnic discrimination, foreigner stress, and family economic stress-separately. Consistent indirect effects of higher levels of concurrent sociocultural risk factors on a lower probability of COVID-19 vaccine uptake were observed to occur through less knowledge about the COVID-19 vaccines and less positive attitudes toward the COVID-19 vaccines at Wave 4. Significant direct effects, but in opposite directions, were found for the associations between Wave 1 ethnic discrimination/Wave 4 daily discrimination and the probability of COVID-19 vaccine uptake. The findings highlight the importance of considering prior and concurrent sociocultural antecedents and the Knowledge-Attitude-Behavior pathway leading to COVID-19 vaccination uptake among Mexican-origin youth and suggest that the impact of discrimination on COVID-19 vaccination uptake may depend on the type (e.g., daily or ethnic) and the context (e.g., during the COVID-19 pandemic or not) of discrimination experienced.

19.
Pestic Biochem Physiol ; 202: 105914, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38879295

ABSTRACT

Indoor cases of Tetranychus cinnabarinus displaying resistance have been documented, but the resistance level in field populations remains unexplored in China. This study delves into the resistance dynamics of T. cinnabarinus to fenpropathrin in various field populations across China, a pressing concern in contemporary agricultural pest control. The conventional bioassay and amplicon sequencing reveal a notable absence of significant fenpropathrin resistance in field populations, contrasting with known resistance in indoor cases. Current study highlights the limitations of traditional bioassays in detecting early-stage resistance and underscores the nuanced capabilities and constraints of amplicon sequencing in resistance gene frequency analysis. By employing an integrated approach, we combined dose-response bioassays, amplicon sequencing, and statistical modeling to assess resistance levels and investigate underlying genetic factors. The model with empirical data indicates that a 5% mutation frequency represents the threshold before resistance emerges. However, the detection of the kdr mutation in certain populations ranging from 0 to 1.2%, signals an early looming threat of future resistance emergence. Additionally, we further assessed a specific dsRNA targeting VGSC genes at two concentrations (10 ng/µL and 100 ng/µL), both inducing substantial mortality by silencing target genes effectively. The exploration of RNA interference (RNAi) as a novel, more environmentally friendly pest control measure opens new avenues, despite the ongoing challenge of resistance evolution. Overall, this study underscores the necessity for evolving pest management strategies, integrating advanced biotechnological approaches with traditional methods, to effectively counter pesticide resistance and ensure sustainable agricultural productivity.


Subject(s)
Insecticide Resistance , Pyrethrins , RNA Interference , Tetranychidae , Animals , Tetranychidae/genetics , Tetranychidae/drug effects , Pyrethrins/pharmacology , Insecticide Resistance/genetics , Insecticides/pharmacology
20.
Toxicon ; 247: 107822, 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38908528

ABSTRACT

To date there are only pirfenidone (PFD) and nintedanib to be given conditional recommendation in idiopathic pulmonary fibrosis (IPF) therapies with slowing disease progression, but neither has prospectively shown a reduced mortality. It is one of the urgent topics to find effective drugs for pulmonary fibrosis in medicine. Previous studies have demonstrated that microcystin-RR (MC-RR) effectively alleviates bleomycin-induced pulmonary fibrosis, but the mechanism has not been fully elucidated yet. We further conducted a comparison of therapeutic effect on the model animals of pulmonary fibrosis between MC-RR and PFD with histopathology and the expression of the molecular markers involved in differentiation, proliferation and metabolism of myofibroblasts, a major effector cell of tissue fibrosis. The levels of the enzyme molecules for maintaining the stability of interstitial structure were also evaluated. Our results showed that MC-RR and PFD effectively alleviated pulmonary fibrosis in model mice with a decreased signaling and marker molecules associated with myofibroblast differentiation and lung fibrotic lesion. In the meantime, both MC-RR and PFD treatment are beneficial to restore molecular dynamics of interstitial tissue and maintain the stability of interstitial architecture. Unexpectedly, MC-RR, rather than PFD, showed a significant effect on inhibiting PKM2-HIF-1α signaling and reducing the level of p-STAT3. Additionally, MC-RR showed a better inhibition effect on FGFR1 expression. Given that PKM2-HIF-1α and activated STAT3 molecular present a critical role in promoting the proliferation of myofibroblasts, MC-RR as a new strategy for IPF treatment has potential advantage over PFD.

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