Chinese mothers' profiles of color-conscious socialization and social dominance orientation: Relations to children's racial attitudes.

OBJECTIVES: This study concerns Chinese mothers' color-conscious socialization and social dominance orientation and how these relate to children's racial attitudes. METHOD: Data were collected from a sample of 155 Chinese children (71 girls) aged 7-11 years and their mothers, from urban regions across China (Shanghai, Jinan, and cities in Jiangsu Province), including observations of mothers' color-conscious practices, self-reported social dominance orientation, and children's attitudes toward light-skinned Chinese, tan-skinned Chinese, and White groups. All children were born in urban areas and from middle-income families. RESULTS: Variable- and person-centered analyses suggested three areas of color-conscious practices, racial appearance, cultural background, and grouping, and revealed heterogeneity in associations between color consciousness and social dominance orientation. Mothers' acknowledgment of shared culture was associated with children's positive attitudes toward their racial ingroup with darker skin tone. CONCLUSIONS: This study emphasizes the importance of a nuanced and contextualized understanding of color-conscious socialization. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Optimization of the extraction process of total steroids from Phillinus gilvus (Schwein.) Pat. by artificial neural network (ANN)-response surface methodology and identification of extract constituents.

Phillinus gilvus (Schwein.) Pat has pharmacological effects such as tonifying the spleen, dispelling dampness, and strengthening the stomach, in which sterol is one of the main compounds of P. gilvus, but there has not been thought you to its extraction and detailed identification of its composition, in the present study, we used artificial neural network (ANN) and response surface methodology (RSM) to optimize the conditions of ultrasonic-assisted extraction, and the parameters of the independent and interaction effects were evaluated. Ultra performance liquid chromatography-quadrupole-time of flight mass spectrometry (UPLC-Q-TOF-MS/MS) was used to identify the major components in the purified extract. The results showed that the optimal extraction process conditions were: ultrasonic time 96 min, ultrasonic power 140 W, liquid to material ratio 1:25 g/ml, and ultrasonic temperature 30.7 °C. The compliance rates of the predicted and experimental values for the artificial neural network model and the response surface model were 98.3% and 96.12%, respectively, indicating that both models have the potential to be used for optimizing the extraction process of P. gilvus in industry. A total of 120 compounds and 30 major steroids were identified by comparison with the reference compounds. Among the major steroidal components are these findings will contribute to the isolation and utilization of active ingredients in P. gilvus.

Changes of crystalline structure and physicochemical properties of Pueraria lobata var. thomsonii starch under water deficit.

Crystal type is an important physicochemical property of starch. However, it is currently unclear whether changes in crystal type affect other properties of starch. This study discovered that water deficit resulted in an increase in small starch granules and transparency in Pueraria lobata var. thomsonii, while causing a decrease in amylose content and swelling power. Additionally, the crystal type of P. Thomsonii starch changed from CB-type to CA-type under water deficit, without significantly altering the short-range ordered structure and chain length distribution of starch. This transformation in crystal type led to peak splitting in the DSC heat flow curve of starch, alterations in gelatinization behavior, and an increase in resistant starch content. These changes in crystalline structure and physicochemical properties of starch granules are considered as adaptive strategies employed by P. Thomsonii to cope with water deficit.

Clinical and hematological characteristics of children infected with the omicron variant of SARS-CoV-2: role of the combination of the neutrophil: lymphocyte ratio and eosinophil count in distinguishing severe COVID-19.

Purpose: Investigate the clinical/hematological characteristics of children infected with the Omicron variant of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) and identify an effective indicator to distinguish coronavirus disease 2019 (COVID-19) severity in children. Methods: A retrospective study was conducted through electronic medical records from pediatric patients. The demographic, clinical, and routine blood test (RBT) features of children diagnosed by real-time PCR for SARS-CoV-2 were collected. Results: Data of 261 patients were analyzed. The most common abnormality shown by RBTs was increased monocyte count (68%). Children had "mild-moderate" or "severe" forms of COVID-19. Prevalence of abnormal neutrophil count (p = 0.048), eosinophil count (p = 0.006), mean corpuscular volume (p = 0.033), mean platelet volume (p = 0.006), platelet-large cell ratio (p = 0.043), and red blood cell distribution width-standard deviation (p = 0.031) were significantly different in the two types. A combination of the neutrophil: lymphocyte ratio (NLR) and eosinophil count for diagnosing severe COVID-19 presented the largest AUC (0.688, 95% CI = 0.599-0.777; p < 0.001), and the AUC increased with a decrease in age. Conclusions: Combination of the NLR and eosinophil count might be a promising indicator for identifying severe COVID-19 in children at infection onset.

Droplet digital molecular beacon-LAMP assay via pico-injection for ultrasensitive detection of pathogens.

A pico-injection-aided digital droplet detection platform is presented that integrates loop-mediated isothermal amplification (LAMP) with molecular beacons (MBs) for the ultrasensitive and quantitative identification of pathogens, leveraging the sequence-specific detection capabilities of MBs. The microfluidic device contained three distinct functional units including droplet generation, pico-injection, and droplet counting. Utilizing a pico-injector, MBs are introduced into each droplet to specifically identify LAMP amplification products, thereby overcoming issues related to temperature incompatibility. Our methodology has been validated through the quantitative detection of Escherichia coli, achieving a detection limit as low as 9 copies/µL in a model plasmid containing the malB gene and 3 CFU/µL in a spiked milk sample. The total analysis time was less than 1.5 h. The sensitivity and robustness of this platform further demonstrated the potential for rapid pathogen detection and diagnosis, particularly when integrated with cutting-edge microfluidic technologies.

Jet dynamics of a cavitation bubble near unequal-sized dual particles.

The jet dynamics of a cavitation bubble near unequal-sized dual particles is investigated employing OpenFOAM, and the effects of the jets on the particles are quantitatively analyzed in terms of their pressure impacts. Different from single-particle cases, the necks that evolve between dual particles are closely linked to the formation mechanism of the jets. Based on the simulation results, the jet dynamics can be divided into five scenarios: (1) the contraction of the annular depression produced by the collision of the two necks causes the bubble to split into two daughter bubbles and generates a single jet inside each daughter bubble; (2) the annular depression impacts the particle, leading to the bubble to fracture and producing a single jet inside a daughter bubble; (3) the bubble is split by a single neck constriction and produces a single jet; (4) the bubble is split by a single neck constriction and generates two jets; and (5) the bubble is split by the contraction of two necks and produces four jets together with three daughter bubbles. As the bubble-particle distance or the radius ratio of the dual particles increases, the maximum force on the small particle generated by the bubble decreases.

Bispecific antibodies targeting two glycoproteins on SFTSV exhibit synergistic neutralization and protection in a mouse model.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with a high fatality rate of up to 30% caused by SFTS virus (SFTSV). However, no specific vaccine or antiviral therapy has been approved for clinical use. To develop an effective treatment, we isolated a panel of human monoclonal antibodies (mAbs). SF5 and SF83 are two neutralizing mAbs that recognize two viral glycoproteins (Gn and Gc), respectively. We found that their epitopes are closely located, and we then engineered them as several bispecific antibodies (bsAbs). Neutralization and animal experiments indicated that bsAbs display more potent protective effects than the parental mAbs, and the cryoelectron microscopy structure of a bsAb3 Fab-Gn-Gc complex elucidated the mechanism of protection. In vivo virus passage in the presence of antibodies indicated that two bsAbs resulted in less selective pressure and could efficiently bind to all single parental mAb-escape mutants. Furthermore, epitope analysis of the protective mAbs against SFTSV and RVFV indicated that they are all located on the Gn subdomain I, where may be the hot spots in the phleboviruses. Collectively, these data provide potential therapeutic agents and molecular basis for the rational design of vaccines against SFTSV infection.

A computed tomography-based nomogram for neoadjuvant chemotherapy plus immunotherapy response prediction in patients with advanced esophageal squamous cell carcinoma.

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.

Investigation of mechanisms of shock wave generation by collapse of cavitation bubbles near particles.

The mechanism of generation of shock waves by the collapse of a cavitation bubble near a single particle or dual particles is numerically investigated using OpenFOAM. For the single-particle case, shock waves during bubble inception and jet impacting on the particle surface are revealed in detail. The pressure induced on the particle by the inception shock wave of the bubble decreases with increasing bubble-particle distance, and the pressure is proportional to 1/r1.26 (r being the distance from the center of the shock wave). For the dual particles, the evolution of the neck structure is closely related to the generation mechanism of the shock wave. At extremely close particle-bubble distances, two shock waves propagating in opposite directions are emitted outside and inside the bubble after two necks collide. At long particle-bubble distances, a shock wave is emitted after the neck contracts, and simultaneously the bubble splits into two daughter bubbles. The energy of the shock wave generated by the neck constriction (i.e., the pressure at its generation location) first increases and then decreases with increasing bubble-particle distance. For unequal-sized double particles, the size of the daughter bubble depends on the bubble-particle distance and the particle size. These findings provide new perspectives for understanding the damage sustained by hydro-mechanical components operating in sand-laden water flows.

Changes of Active Substances in Ganoderma lucidum during Different Growth Periods and Analysis of Their Molecular Mechanism.

Ganoderma lucidum, renowned as an essential edible and medicinal mushroom in China, remains shrouded in limited understanding concerning the intrinsic mechanisms governing the accumulation of active components and potential protein expression across its diverse developmental stages. Accordingly, this study employed a meticulous integration of metabolomics and proteomics techniques to scrutinize the dynamic alterations in metabolite accumulation and protein expression in G. lucidum throughout its growth phases. The metabolomics analysis unveiled elevated levels of triterpenoids, steroids, and polyphenolic compounds during the budding stage (BS) of mushroom growth, with prominent compounds including Diplazium and Ganoderenic acids E, H, and I, alongside key steroids such as cholesterol and 4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol. Additionally, nutrients such as polysaccharides, flavonoids, and purines exhibited heightened presence during the maturation stage (FS) of ascospores. Proteomic scrutiny demonstrated the modulation of triterpenoid synthesis by the CYP450, HMGR, HMGS, and ERG protein families, all exhibiting a decline as G. lucidum progressed, except for the ARE family, which displayed an upward trajectory. Therefore, BS is recommended as the best harvesting period for G. lucidum. This investigation contributes novel insights into the holistic exploitation of G. lucidum.

Physiological, cytological and multi-omics analysis revealed the molecular response of Fritillaria cirrhosa to Cd toxicity in Qinghai-Tibet Plateau.

Fritillaria cirrhosa, an endangered plant endemic to plateau regions, faces escalating cadmium (Cd) stress due to pollution in the Qinghai-Tibet Plateau. This study employed physiological, cytological, and multi-omics techniques to investigate the toxic effects of Cd stress and detoxification mechanisms of F. cirrhosa. The results demonstrated that Cd caused severe damage to cell membranes and organelles, leading to significant oxidative damage and reducing photosynthesis, alkaloid and nucleoside contents, and biomass. Cd application increased cell wall thickness by 167.89% in leaves and 445.78% in bulbs, leading to weight percentage of Cd increases of 76.00% and 257.14%, respectively. PER, CESA, PME, and SUS, genes responsible for cell wall thickening, were significantly upregulated. Additionally, the levels of metabolites participating in the scavenging of reactive oxygen species, including oxidized glutathione, D-proline, L-citrulline, and putrescine, were significantly increased under Cd stress. Combined multi-omics analyses revealed that glutathione metabolism and cell wall biosynthesis pathways jointly constituted the detoxification mechanism of F. cirrhosa in response to Cd stress. This study provides a theoretical basis for further screening of new cultivars for Cd tolerance and developing appropriate cultivation strategies to alleviate Cd toxicity.

Tetrahydroxy stilbene glucoside rejuvenates aging hematopoietic stem cells with predilection for lymphoid differentiation via AMPK and Tet2.

INTRODUCTION: Aging of hematopoietic stem cells (HSCs) has emerged as an important challenge to human health. Recent advances have raised the prospect of rejuvenating aging HSCs via specific medical interventions, including pharmacological treatments. Nonetheless, efforts to develop such drugs are still in infancy until now. OBJECTIVES: We aimed to screen the prospective agents that can rejuvenate aging HSCs and explore the potential mechanisms. METHODS: We screened a set of natural anti-aging compounds through oral administration to sub-lethally irradiated mice, and identified 2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside (TSG) as a potent rejuvenating agent for aging HSCs. Then naturally aged mice were used for the follow-up assessment to determine the HSC rejuvenating potential of TSG. Finally, based on the transcriptome and DNA methylation analysis, we validated the role of the AMP-activated protein kinase (AMPK)-ten-eleven-translocation 2 (Tet2) axis (the AMPK-Tet2 axis) as the underlying mechanisms of TSG for ameliorating HSCs aging. RESULTS: TSG treatment not only significantly increased the absolute number of common lymphoid progenitors (CLPs) along with B lymphocytes, but also boosted the HSCs/CLPs repopulation potential of aging mice. Further elaborated mechanism research demonstrated that TSG supplementation restored the stemness of aging HSCs, as well as promoted an epigenetic reprograming that was associated with an improved regenerative capacity and an increased rate of lymphopoiesis. Such effects were diminished when the mice were co-treated with an AMPK inhibitor, or when it was performed in Tet2 knockout mice as well as senescent cells assay. CONCLUSION: TSG is effective in rejuvenating aging HSCs by modulating the AMPK- Tet2 axis and thus represents a potential candidate for developing effective HSC rejuvenating therapies.

Metabolomic Analysis in Saliva and Different Brain Regions of Older Mice with Postoperative Delirium Behaviors.

Objective: Postoperative delirium (POD) has become a critical challenge with severe consequences and increased incidences as the global population ages. However, the underlying mechanism is yet unknown. Our study aimed to explore the changes in metabolites in three specific brain regions and saliva of older mice with postoperative delirium behavior and to identify potential non-invasive biomarkers. Methods: Eighteen-month-old male C57/BL6 mice were randomly assigned to the anesthesia/surgery or control group. Behavioral tests were conducted 24 h before surgery and 6, 9, and 24 h after surgery. Complement C3 (C3) and S100 calcium-binding protein B protein (S100beta) levels were measured in the hippocampus, and a metabolomics analysis was performed on saliva, hippocampus, cortex, and amygdala samples. Results: In total, 43, 33, 38, and 14 differential metabolites were detected in the saliva, hippocampus, cortex, and amygdala, respectively. "Pyruvate" "alpha-linolenic acid" and "2-oleoyl-1-palmitoy-sn-glycero-3-phosphocholine" are enriched in one common pathway and may be potential non-invasive biomarkers for POD. Common changes were observed in the three brain regions, with the upregulation of 1-methylhistidine and downregulation of D-glutamine. Conclusion: Dysfunctions in energy metabolism, oxidative stress, and neurotransmitter dysregulation are implicated in the development of POD. The identification of changes in the level of salivary metabolite biomarkers could aid in the development of noninvasive diagnostic methods for POD.

Discovery of Ten Anti-HIV Hit Compounds and Preliminary Pharmacological Mechanisms Studies

BACKGROUND: The research and development of HIV drugs is very important, but at the same time it is a long cycle and expensive system project. High-throughput drug screening systems and molecular libraries of potential hit compounds remain the main ways for the discovery of hit compounds with anti-HIV activity. OBJECTIVE: The aim of this study was to screen out the hit compounds against HIV-1 in the natural product molecule library and the antiviral molecule library, and elucidate the molecular mechanism of their inhibition of HIV-1, so as to provide a new choice for AIDS drug research. METHODS: In this study, a drug screening system using HIV Rev-dependent indicator cell line (Rev-A3R5-GFP reporter cells) with pseudoviruses (pNL4-3) was used. The natural drug molecule library and antiviral molecule library were screened, and preliminary drug mechanism studies were performed. RESULTS: Ten promising hit compounds were screened. These ten molecules and their drug inhibitory IC50 were as follows: Cephaeline (0.50 µM), Yadanziolide A (8.82 µM), Bruceine D (2.48 µM), Astragaloside IV (4.30 µM), RX-3117 (1.32 µM), Harringtonine (0.63 µM), Tubercidin (0.41 µM), Theaflavine-3, 3'-digallate (0.41 µM), Ginkgetin (10.76 µM), ZK756326 (5.97 µM). The results of the Time of additions showed that except for Astragaloside IV and Theaflavine-3, 3'-digallate had a weak entry inhibition effect, and it was speculated that all ten compounds had an intracellular inhibition effect. Cephaeline, Harringtonine, Astragaloside IV, Bruceine D, and Tubercidin may have pre-reverse transcriptional inhibition. Yadanziolide A, Theaflavine-3, 3'-digallate, Ginkgetin and RX-3117 may be in the post-reverse transcriptional inhibition. The inhibitory effect of ZK 75632 may be in the reverse transcriptional process. CONCLUSION: A drug screening system using Rev-A3R5-GFP reporter cells with pseudoviruses (pNL4-3) is highly efficient. This study provided potential hit compounds for new HIV drug research.

DNA methylation clocks for estimating biological age in Chinese cohorts.

Epigenetic clocks are accurate predictors of human chronological age based on the analysis of DNA methylation (DNAm) at specific CpG sites. However, a systematic comparison between DNA methylation data and other omics datasets has not yet been performed. Moreover, available DNAm age predictors are based on datasets with limited ethnic representation. To address these knowledge gaps, we generated and analyzed DNA methylation datasets from two independent Chinese cohorts, revealing age-related DNAm changes. Additionally, a DNA methylation aging clock (iCAS-DNAmAge) and a group of DNAm-based multi-modal clocks for Chinese individuals were developed, with most of them demonstrating strong predictive capabilities for chronological age. The clocks were further employed to predict factors influencing aging rates. The DNAm aging clock, derived from multi-modal aging features (compositeAge-DNAmAge), exhibited a close association with multi-omics changes, lifestyles, and disease status, underscoring its robust potential for precise biological age assessment. Our findings offer novel insights into the regulatory mechanism of age-related DNAm changes and extend the application of the DNAm clock for measuring biological age and aging pace, providing the basis for evaluating aging intervention strategies.

A fluorescent probe for ultrarapid H2O2 detection during reagent-stimulated oxidative stress in cells and zebrafish.

Hydrogen peroxide(H2O2), as a reliable signaling biomolecule for oxidative stress, its accurate detection during agent-stimulated oxidative stress plays a vital role in pathological and physiological mechanism exploration for disease theranostics. It's necessary to develop an efficient method for their detection. In view of the advantages of fluorescent probes, we rationally constructed a novel fluorescent probe Compound 2 based on 4-(Bromomethyl)benzeneboronic acid pinacol ester_Herein, a small molecule fluorescent probe was fabricated using isoflore nitrile as fluorescent group, phenylboronic acid pinacol ester as the response group, to detect H2O2. The probe Compound 2 has a strong fluorescence intensity at 575 nm, indicating that the structure of the probe molecule is reasonably designed, and the Stokes shift is up to 172 nm. While the detection time is as low as 30 s and the LOD of the probe for H2O2 is as low as 3.7 µmol/L,the quantum yield is Φ = 40.31 %. It has been successfully used for imaging detection of H2O2 in HepG2 cells and zebrafish for its low toxicity. It can be found that this small molecule fluorescent probe can identify H2O2 in tumor cells significantly and efficiently, which would realize the early diagnosis of tumor.

A nomogram prediction model for hungry bone syndrome in dialysis patients with secondary hyperparathyroidism after total parathyroidectomy.

OBJECTIVE: Secondary hyperparathyroidism (SHPT) is a common complication of chronic kidney disease (CKD). Hungry bone syndrome (HBS) after parathyroidectomy (PTX) is a serious complication, which can lead to diarrhea, convulsion, arrhythmia and even death. This study was aimed to determine the risk factors for HBS after PTX in dialysis patients with SHPT and construct a nomogram prediction model to predict the incidence of postoperative complications. METHODS: Clinical data were collected from 80 maintenance hemodialysis (MHD) patients with SHPT who received total PTX in the Second Hospital of Jilin University from January 2018 to September 2021. In line with the inclusion and exclusion criteria, totally 75 patients were finally enrolled for analysis. Patients were divided into two groups for retrospective analysis according to the severity of postoperative HBS, including HBS group and non-HBS (N-HBS) group. Univariate and multivariate logistic regression analyses were conducted to determine the risk factors for postoperative HBS. Afterwards, the receiver operating characteristic (ROC) curves were plotted based on the statistical analysis results, aiming to compare the prediction effects of different predicting factors. Finally, the nomogram was established to evaluate the occurrence probability of postoperative complications predicted by the risk factors. RESULTS: Among the 75 patients, 32 had HBS (HBS group), while 43 did not have HBS (N-HBS group). Univariate analysis results indicated that, the preoperative intact parathyroid hormone (iPTH) and serum alkaline phosphatase (ALP) levels in HBS group were significantly higher than those in N-HBS group, while preoperative hemoglobin and preoperative albumin (Alb) levels were significantly lower than those in N-HBS group. As discovered by multivariate logistic regression analysis, preoperative iPTH (OR = 1.111, P = 0.029) and ALP (OR = 1.010, P < 0.001) were the independent risk factors for postoperative HBS. ROC curve analysis suggested that the area under the curve (AUC) values of these two indicators were 0.873 and 0.926, respectively (P < 0.0001). Subsequently, the nomogram model for predicting HBS was constructed. The model verification results indicated that the predicted values were basically consistent with the measured values, with the C-index of 0.943 (95% CI 0.892-0.994). Besides, the calibration curve was consistent with the ideal curve, demonstrating the favorable accuracy and discrimination of the model. CONCLUSIONS: Preoperative iPTH and preoperative ALP are the risk factors for postoperative HBS, which can be used to guide the early clinical intervention.

Role of ferroptosis in chronic kidney disease.

Chronic kidney disease (CKD) has historically been a significant global health concern, profoundly impacting both life and well-being. In the process of CKD, with the gradual loss of renal function, the incidence of various life-threatening complications, such as cardiovascular diseases, cerebrovascular accident, infection and stroke, is also increasing rapidly. Unfortunately, existing treatments exhibit limited ability to halt the progression of kidney injury in CKD, emphasizing the urgent need to delve into the precise molecular mechanisms governing the occurrence and development of CKD while identifying novel therapeutic targets. Renal fibrosis, a typical pathological feature of CKD, plays a pivotal role in disrupting normal renal structures and the loss of renal function. Ferroptosis is a recently discovered iron-dependent form of cell death characterized by lipid peroxide accumulation. Ferroptosis has emerged as a potential key player in various diseases and the initiation of organ fibrosis. Substantial evidence suggests that ferroptosis may significantly contribute to the intricate interplay between CKD and its progression. This review comprehensively outlines the intricate relationship between CKD and ferroptosis in terms of iron metabolism and lipid peroxidation, and discusses the current landscape of pharmacological research on ferroptosis, shedding light on promising avenues for intervention. It further illustrates recent breakthroughs in ferroptosis-related regulatory mechanisms implicated in the progression of CKD, thereby providing new insights for CKD treatment. Video Abstract.

Computed tomography-based nomogram of Siewert type II/III adenocarcinoma of esophagogastric junction to predict response to docetaxel, oxaliplatin and S-1.

BACKGROUND: Neoadjuvant chemotherapy (NAC) has become the standard care for advanced adenocarcinoma of esophagogastric junction (AEG), although a part of the patients cannot benefit from NAC. There are no models based on baseline computed tomography (CT) to predict response of Siewert type II or III AEG to NAC with docetaxel, oxaliplatin and S-1 (DOS). AIM: To develop a CT-based nomogram to predict response of Siewert type II/III AEG to NAC with DOS. METHODS: One hundred and twenty-eight consecutive patients with confirmed Siewert type II/III AEG underwent CT before and after three cycles of NAC with DOS, and were randomly and consecutively assigned to the training cohort (TC) (n = 94) and the validation cohort (VC) (n = 34). Therapeutic effect was assessed by disease-control rate and progressive disease according to the Response Evaluation Criteria in Solid Tumors (version 1.1) criteria. Possible prognostic factors associated with responses after DOS treatment including Siewert classification, gross tumor volume (GTV), and cT and cN stages were evaluated using pretherapeutic CT data in addition to sex and age. Univariate and multivariate analyses of CT and clinical features in the TC were performed to determine independent factors associated with response to DOS. A nomogram was established based on independent factors to predict the response. The predictive performance of the nomogram was evaluated by Concordance index (C-index), calibration and receiver operating characteristics curve in the TC and VC. RESULTS: Univariate analysis showed that Siewert type (52/55 vs 29/39, P = 0.005), pretherapeutic cT stage (57/62 vs 24/32, P = 0.028), GTV (47.3 ± 27.4 vs 73.2 ± 54.3, P = 0.040) were significantly associated with response to DOS in the TC. Multivariate analysis of the TC also showed that the pretherapeutic cT stage, GTV and Siewert type were independent predictive factors related to response to DOS (odds ratio = 4.631, 1.027 and 7.639, respectively; all P < 0.05). The nomogram developed with these independent factors showed an excellent performance to predict response to DOS in the TC and VC (C-index: 0.838 and 0.824), with area under the receiver operating characteristic curve of 0.838 and 0.824, respectively. The calibration curves showed that the practical and predicted response to DOS effectively coincided. CONCLUSION: A novel nomogram developed with pretherapeutic cT stage, GTV and Siewert type predicted the response of Siewert type II/III AEG to NAC with DOS.

MicroRNA-377-3p exacerbates chronic obstructive pulmonary disease through suppressing ZFP36L1 expression and inducing lung fibroblast senescence.

Chronic obstructive pulmonary disease (COPD) is a leading aging related cause of global mortality. Small airway narrowing is recognized as an early and significant factor for COPD development. Senescent fibroblasts were observed to accumulate in lung of COPD patients and promote COPD progression through aberrant extracellular matrix (ECM) deposition and senescence-associated secretory phenotype (SASP). On the basis of our previous study, we further investigated the the causes for the increased levels of miR-377-3p in the blood of COPD patients, as well as its regulatory function in the pathological progression of COPD. We found that the majority of up-regulated miR-377-3p was localized in lung fibroblasts. Inhibition of miR-377-3p improved chronic smoking-induced COPD in mice. Mechanistically, miR-377-3p promoted senescence of lung fibroblasts, while knockdown of miR-377-3p attenuated bleomycin-induced senescence in lung fibroblasts. We also identified ZFP36L1 as a direct target for miR-377-3p that likely mediated its pro senescence activity in lung fibroblasts. Our data reveal that miR-377-3p is crucial for COPD pathogenesis, and may serve as a potential target for COPD therapy.