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The contamination of food and feed by mycotoxins, particularly zearalenone (ZEA) and deoxynivalenol (DON), is a global issue. Prenatal exposure to ZEA and DON can result in congenital cardiac malformations in fetuses. Addressing the prevention and mitigation of embryonic cardiotoxicity caused by these toxins is crucial. Citrus limonoid nomilin (NOM) is an extract known for its pathological properties in various diseases. This study investigated the potential mechanism of NOM in mitigating cardiotoxicity caused by ZEA and DON co-exposure in a zebrafish model. The findings indicated that NOM pretreatment alleviated cardiac developmental toxicity induced by ZEA and DON and normalized the expression of key genes involved in heart development, including gata4, vmhc, nkx2.5, and sox9b. Co-exposure to NOM, ZEA, and DON enhanced SOD and catalase activity, increased glutathione levels, and reduced ROS and malondialdehyde production. Furthermore, NOM reduced cardiac oxidative damage by activating the Keap1/Nrf2 signaling pathway. In summary, this study offers new insights for preventive interventions against congenital heart disease caused by mycotoxin exposure., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: We aimed to probe the diagnostic value of transvaginal color Doppler ultrasound (TV-CDU) parameters in cesarean scar pregnancy (CSP) and CSP sub-types, and the relevant factors affecting patients' surgical effects., Methods: Seventy-five CSP patients (all requested termination of pregnancy) were selected as the observation group, and 75 normal pregnant women with a history of cesarean section were selected as the control group. All the study subjects underwent TV-CDU and their cesarean scar muscle (CSM) thickness, minimum sagittal muscle thickness and resistance index (RI) of blood flow in the anterior wall of the lower uterine segment were calculated. The diagnostic value of CSM, minimum sagittal muscle thickness, and RI for CSP and CSP sub-types was analyzed. The patients in the observation group were grouped into the effective group and the ineffective group according to whether the surgical treatment was effective or not, and the independent factors affecting CSP efficacy were analyzed., Results: The observation group had lower CSM, minimum sagittal muscle thickness and RI than the control group. CSM, RI, and minimum sagittal thickness in patients with type II CSP were lower than those in patients with type I, and these indicators in patients with type III were lower than those in patients with type II. The area under the curve (AUC) of CSM, RI and minimum sagittal muscle thickness in combination for CSP diagnosis and the AUC for CSP sub-types were higher than those of each indicator alone. Gestational sac size and CSM were independent factors affecting CSP treatment., Conclusion: Changes in TV-CDU parameters facilitates CSP diagnosis after cesarean section. CSM, minimum sagittal muscle thickness changes, and RI in combination possesses high value for CSP diagnosis and CSP sub-types. Gestational sac size and CSM are independent factors affecting CSP treatment., (© 2024. The Author(s).)

Camellia oleifera is a crop of high economic value, yet it is particularly susceptible to various diseases and pests that significantly reduce its yield and quality. Consequently, the precise segmentation and classification of diseased Camellia leaves are vital for managing pests and diseases effectively. Deep learning exhibits significant advantages in the segmentation of plant diseases and pests, particularly in complex image processing and automated feature extraction. However, when employing single-modal models to segment Camellia oleifera diseases, three critical challenges arise: (A) lesions may closely resemble the colors of the complex background; (B) small sections of diseased leaves overlap; (C) the presence of multiple diseases on a single leaf. These factors considerably hinder segmentation accuracy. A novel multimodal model, CNN-Transformer Dual U-shaped Network (CTDUNet), based on a CNN-Transformer architecture, has been proposed to integrate image and text information. This model first utilizes text data to address the shortcomings of single-modal image features, enhancing its ability to distinguish lesions from environmental characteristics, even under conditions where they closely resemble one another. Additionally, we introduce Coordinate Space Attention (CSA), which focuses on the positional relationships between targets, thereby improving the segmentation of overlapping leaf edges. Furthermore, cross-attention (CA) is employed to align image and text features effectively, preserving local information and enhancing the perception and differentiation of various diseases. The CTDUNet model was evaluated on a self-made multimodal dataset compared against several models, including DeeplabV3+, UNet, PSPNet, Segformer, HrNet, and Language meets Vision Transformer (LViT). The experimental results demonstrate that CTDUNet achieved an mean Intersection over Union (mIoU) of 86.14%, surpassing both multimodal models and the best single-modal model by 3.91% and 5.84%, respectively. Additionally, CTDUNet exhibits high balance in the multi-class segmentation of Camellia oleifera diseases and pests. These results indicate the successful application of fused image and text multimodal information in the segmentation of Camellia disease, achieving outstanding performance.

Objective: To assess the diagnostic efficacy of the CEUS LI-RADS combined with a model constructed on the basis of age, sex, AFP, and PIVKA-II (ASAP) for the diagnosis of HCC in high-risk patients., Methods: This retrospective study included 366 liver lesions from 366 patients who underwent liver CEUS. All liver lesions were characterized and categorized according to CEUS LI-RADS v2017. Two modified methods were applied: LR-3/4/M nodules accompanied by AFP > 200 ng/mL (Criterion 2) or ASAP model score > 0.5256 and CA 19-9 in the normal range (Criterion 3) were recategorized as LR-5. The reference criteria included histopathological or comprehensive imaging and the clinical follow-up results. The diagnostic performance was evaluated and compared by the sensitivity, specificity, PPV, and NPV., Results: The incidence of HCC in LR-3, LR-4, LR-5, and LR-M was 33.3% (4/12), 86.4% (38/44), 98.5% (191/194) and 82.7% (81/98), respectively. After using Criterion 2 compared to CEUS LI-RADS v2017, the sensitivity of the modified LR-5 for diagnosing HCC increased from 60.8% to 70.7% (p < 0.01) with little effect on its specificity (94.2% vs. 92.3%, p = 1.00) or PPV (98.5% vs. 98.2%, p = 0.86). After using Criterion 3, the sensitivity of the modified LR-5 for the diagnosis of HCC was further improved to 86.9% (p < 0.01), and its specificity and PPV were not significantly changed (92.3% and 98.6%, both p > 0.05)., Conclusion: CEUS LI-RADS combined with the serum biomarker-based ASAP model improved the sensitivity of LR-5 in diagnosing HCC with little effect on its specificity and PPV., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest., (Copyright © 2024 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) is a novel MRI technology to image certain compounds at extremely low concentrations. Long acquisition time to measure signals at a set of offset frequencies of the Z-spectra and to repeat measurements to reduce noise pose significant challenges to its applications. This study explores correlations of CEST MR images along the spatial and Z-spectral dimensions to improve MR image quality and robustness of magnetization transfer ratio (MTR) asymmetry estimation via a joint k -ω reconstruction model. The model was formulated as an optimization problem with respect to MR images at all frequencies ω, while incorporating regularizations along the spatial and spectral dimensions. The solution was subject to a self-consistency condition that the Z-spectrum of each pixel follows a multi-peak data fitting model corresponding to different CEST pools. The optimization problem was solved using the alternating direction method of multipliers. The proposed joint reconstruction method was evaluated on a simulated CEST MRI phantom and semi-experimentally on choline and iopamidol phantoms with added Gaussian noise of various levels. Results demonstrated that the joint reconstruction method was more tolerable to noise and reduction in number of offset frequencies by improving signal-to-noise ratio (SNR) of the reconstructed images and reducing uncertainty in MTR asymmetry estimation. In the choline and iopamidol phantom cases with 10.5% noise in the measurement data, our method achieved an averaged SNR of 31.0 dB and 32.2 dB compared to the SNR of 24.7 dB and 24.4 dB in the conventional reconstruction approach. It reduced uncertainty of the MTR asymmetry estimation over all regions of interest by 54.4% and 43.7%, from 1.71 and 2.38 to 0.78 and 1.71, respectively.

Competing Interests: The authors report no conflicts of interest in this work.

Sirtuins (SRTs) are a group of nicotinamide adenine dinucleotide (NAD + )-dependent deacetylase that target both histone and nonhistone proteins. The biological function of SRT in horticultural plants has been rarely studied. In this study, FaSRT1-2 was identified as a key member of the 8 FaSRTs encoded in cultivated strawberry genome. Transient overexpression of FaSRT1-2 in strawberry fruit accelerated ripening, increased the content of anthocyanins and sugars, enhanced ripening-related gene expression. Moreover, stable transformation of FaSRT1-2 in strawberry plants resulted in enhanced vegetative growth, increased sensitivity to heat stress and increased susceptibility to Botrytis cinerea infection. Interestingly, knocking out the homologous gene in woodland strawberry had the opposite effects. Additionally, we found the content of stress-related hormone abscisic acid (ABA) was decreased, while the growth-related gibberellin (GA) concentration was increased in FaSRT1-2 overexpression lines. Gene expression analysis revealed induction of heat shock proteins, transcription factors, stress-related and antioxidant genes in the FaSRT1-2-overexpressed plants while knocked-out of the gene had the opposite impact. In conclusion, our findings demonstrated that FaSRT1-2 could positively promote strawberry plant vegetative growth and fruit ripening by affecting ABA and GA pathways. However, it negatively regulates the resistance to heat stress and B. cinerea infection by influencing the related gene expression., (© 2024 John Wiley & Sons Ltd.)

Background: With remarkable advancements in assisted reproductive technology (ART), the number of ART-conceived children continues to increase. Despite increased research investigating the outcomes of ART children, evidence on neurodevelopment remains controversial., Objective: The aim of this study was to investigate the association between ART use and neurodevelopment in children at 1 year of age and to determine whether the characteristics of parental infertility and specific ART procedures affect neurodevelopment in children., Study Design: The Jiangsu Birth Cohort enrolled couples who received ART treatment and who conceived spontaneously (2014-2020) in Jiangsu Province, China. In this study, we included 3531 pregnancies with 3840 cohort children who completed neurodevelopment assessment at 1 year of age, including 1906 infants conceived by ART (including 621 twins). Poisson regressions were fitted to estimate unadjusted and adjusted risk ratios (RRs) and 95% confidence intervals (CIs) for ART use with neurodevelopmental outcomes (cognition, receptive communication, expressive communication, fine motor, and gross motor) in children., Results: Among singletons, ART use was associated with a 24% to 34% decrease in the risk for noncompetent development in 3 domains (cognition, adjusted RR, 0.66; 95% CI, 0.53-0.82; receptive communication, 0.76; 0.64-0.91; expressive communication, 0.69; 0.51-0.93) after adjustment for conventional covariates. However, an inverse association was observed in the gross motor domain, with ART singletons having a greater risk of being noncompetent in gross motor development than their non-ART counterparts (adjusted RR, 1.41; 95% CI, 1.11-1.79). Compared with singletons, twins resulting from ART treatment demonstrated compromised neurodevelopment in several domains. Furthermore, we continued to observe that the transfer of 'poor' quality embryos was associated with greater risks for noncompetent development in receptive communication (adjusted RR, 1.50; 95% CI, 1.05-2.14) and gross motor domains (1.55; 1.02-2.36) among ART singletons., Conclusion: These results generally provide reassuring evidence among singletons born after ART in the cognition, communication, and fine motor domains, but drawn attention to their gross motor development. The quality of transferred embryos in ART treatment might be associated with offspring neurodevelopment; however, the potential associations warrant further validation in independent studies, and the clinical significance needs careful interpretation., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Organic frameworks-based batteries with excellent physicochemical stability and long-term high capacity will definitely reduce the cost, carbon emissions, and metal consumption and contamination. Here, an ultra-stable and ultra-thin perylene-dicyandiamide-based hydrogen organic framework (HOF) nanosheet (P-DCD) of ≈3.5 nm in thickness is developed. When applied in the cathode, the P-DCD exhibits exceptional long-term capacity retention for alkali-ion batteries (AIBs). Strikingly, for lithium-ion batteries (LIBs), at current of 2 A g -1 , the large reversible capacity of 108 mA h g -1 shows no attenuation within 5 000 cycles. For sodium-ion batteries (SIBs), the related capacity retains 91.7% within 10 000 cycles compared to the initial state, significantly much more stable than conventional organic materials reported previously. Mechanism studies through ex situ and in situ experiments and theoretical density functional theory (DFT) calculations reveal that the impressive long-term performance retention originates from the large electron delocalization, fast ion diffusion, and physicochemical stability within the ultra-thin 2D P-DCD, featuring π-π and hydrogen bonding stacking, nitrogen-rich units, and low impedance. The advantageous features demonstrate that rationally designed stable and effective organic frameworks pave the way to utilizing complete organic materials for developing next-generation low-cost and highly stable energy storage batteries., (© 2023 Wiley‐VCH GmbH.)

Background: Huaier granule is an important medicinal fungus extract widely used in cancer treatment. Previous retrospective studies have reported its effectiveness in breast cancer patients, but the imbalanced baseline characteristics of participants could have biased the results. Therefore, this retrospective study aimed to examine the efficacy of Huaier granule on the prognosis of breast cancer patients., Methods: In this single-center cohort study, breast cancer patients diagnosed and treated at the Guangdong Provincial Hospital of Chinese Medicine between 2009 and 2017 were selected. The data were retrospectively analyzed and divided into two groups according to whether the patients received Huaier granules. The propensity score matching (PSM) method was used to eliminate selection bias. The disease-free survival (DFS) and overall survival (OS) for these groups were compared using the Kaplan-Meier method and the Cox regression., Results: This study included 214 early invasive breast cancer patients, 107 in the Huaier group and 107 in the control group. In the Kaplan-Meier analysis, the 2-year and 5-year DFS rates were significantly different in the Huaier group and control group (hazard ratio [HR], 0.495; 95% confidence interval [CI], 0.257-0.953; P = 0.023). The 2-year and 5-year OS rates were also significantly different (HR, 0.308; 95% CI, 0.148-0.644; P = 0.001). On multivariable Cox regression, Huaier granule was associated with improved DFS (HR, 0.440; 95% CI, 0.223-0.868; P = 0.018) and OS (HR, 0.236; 95% CI, 0.103-0.540; P = 0.001)., Conclusion: In this retrospective study, Huaier granules improved the DFS and OS of early invasive breast cancer patients, providing real-world evidence for further prospective studies on treating breast cancer with Huaier granules., (Copyright © 2024 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Context: Adequate maternal thyroid hormone is vital for fetal neurodevelopment. Abnormal thyroid function can cause developmental defects in offspring from spontaneous pregnancies; however, research in assisted reproduction is lacking., Objectives: To investigate the association between thyroid disorders and offspring neurodevelopment from assisted reproduction., Design: Prospective cohort study., Setting and Participants: In this prospective and longitudinal birth cohort study (Jiangsu, China), we included 729 women who had their thyroid function tested before ART cycle and delivered liveborn babies between November 2015 and June 2020., Main Outcome Measures: Maternal thyroid function was assessed by measuring thyroid antibodies, free thyroxine, and serum thyroid-stimulating hormone. The third edition Bayley Scales of Infant and Toddler Development screening test (Bayley-III screening test) is used to assess the infant's neurodevelopment., Results: In multivariate corrected linear regression analysis, infants of women with subclinical hypothyroidism demonstrated a significantly lower receptive communication score (β = -0.63, 95% CI [-1.12, -0.14], P = 0.013), with stratified analysis showing a significant association among female offspring (β = -0.87, 95% CI [-1.59, -0.15], P = 0.018) but null association among male offspring (β = -0.44, 95% CI [-1.03, 0.15], P = 0.145). No significant differences were found in assisted pregnancy population with normal thyroid function and positive antibodies according to the diagnostic cut-offs applied to normal pregnant women., Conclusions: Subclinical hypothyroidism in assisted pregnancies correlates with lower communication scores in 1-year-olds, especially in girls. Recommending medication for subclinical hypothyroidism throughout, regardless of thyroid autoantibody status., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The occurrence of benign prostate hyperplasia (BPH) was related to disrupted sex steroid hormones, and metformin (Met) had a clinical response to sex steroid hormone-related gynaecological disease. However, whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear. Here, our clinical study showed that along with prostatic epithelial cell (PEC) proliferation, sex steroid hormones were dysregulated in the serum and prostate of BPH patients. As the major contributor to dysregulated sex steroid hormones, elevated dihydrotestosterone (DHT) had a significant positive relationship with the clinical characteristics of BPH patients. Activation of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor (AR)-mediated Yes-associated protein (YAP1)-TEA domain transcription factor (TEAD4) heterodimers. Met's anti-proliferative effects were blocked by AMPK inhibitor or YAP1 overexpression in DHT-cultured BPH-1 cells. Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation., Competing Interests: The authors declare that there are no conflicts of interest., (© 2023 The Authors.)

Growing empirical evidence shows that circular RNAs (circRNAs) are implicated in tumor pathogenesis. However, little is known about the mechanism by which circRNAs contribute to the progression of adenocarcinoma of the esophagogastric junction (AEG). We conducted RNA high-throughput sequencing and bioinformatic analyses on 22 AEG tissues and their matching healthy gastric mucosal tissues and found that circRNA0007766 may act as a tumor promoter in AEG pathogenesis. BaseScope® in situ hybridization revealed that circRNA0007766 was strongly upregulated in AEG. We then constructed co-expression and ceRNA networks to elucidate the relationships among specific circRNAs, microRNAs (miRNAs), and mRNAs. We also demonstrated that circRNA0007766 acted as the sponge of miR-34c-5p, thereby positively regulating cyclin D1. In vivo and in vitro experiments demonstrated the roles of circRNA0007766 in promoting AEG progression and invasion. AEG tissues are characterized by circRNA0007766 upregulation which is correlated with lymph node metastasis and poor survival. To the best of our knowledge, the present study is one of the first to show that the circRNA0007766/miR-34c-5p/cyclin D1 axis is important in AEG progression. Furthermore, the results of this work imply that circRNA0007766 is potentially a novel AEG biomarker., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Feng Wu reports administrative support and equipment, drugs, or supplies were provided by Department of Tumor Biobank, Shanxi Province Cancer Hospital., (Copyright © 2023 Elsevier Inc. All rights reserved.)

N-nitroso compounds (NOCs) exposure is a major risk factor for the development of gastric cancer. However, the carcinogenic mechanisms by which NOCs induce gastric and other cancers, especially the NOCs-induced Warburg effect, have not been comprehensively studied. Lactate dehydrogenase (LDH), which has two subunits (LDHA and LDHB), plays an important role in the Warburg effect of tumor cells. Therefore, we hypothesized that LDHA and LDHB could promote Warburg effect in malignant transformed GES-1 cells induced by Nmethyl-N'-nitro-N-nitrosoguanidine (MNNG). GES-1 cells were exposed to 1 μmol/L MNNG and cultured for 40 passages. During the culturing process, cell proliferation, migration, and soft agar colony formation significantly increased after 30 passages. Following MNNG exposure, lactate, LDH, glucose uptake, and the expression levels of key enzymes in glycolysis were significantly increased. Knocking down LDHA or LDHB alone reduced lactate secretion, inhibited cell viability, and impaired migratory capacities. Knocking down LDHA and LDHB together fully suppressed lactate secretion and effectively suppressed the malignant phenotype of cells transformed by long-term MNNG exposure. Finally, we demonstrated that overexpression of LDHA and LDHB promotes the malignant transformation of GES-1 cells by enhancing the Warburg effect during long-term exposure to NOCs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objectives: To compare the inter-modality consistency and diagnostic performances of the contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) and contrast-enhanced computed tomography (CECT) LI-RADS in patients at risk for hepatocellular carcinoma (HCC), so as to help clinicians to select a more appropriate modality to follow the focal liver lesions (FLLs)., Methods: This retrospective study included untreated 277 FLLs from 247 patients who underwent both CEUS and CECT within 1 month. The ultrasound contrast medium used was SonoVue. FLL categories were independently assigned by two ultrasound physicians and two radiologists using CEUS LI-RADS v2017 and CECT LI-RADS v2018, respectively. The diagnostic performances of CEUS and CECT LI-RADS were evaluated using sensitivity, specificity, positive predictive value (PPV), and negative predictive value. Cohen's Kappa was employed to evaluate the concordance of the LI-RADS category., Results: The inter-modality consistency for CEUS and CECT LI-RADS was 0.31 (p < 0.001). HCC was more frequently observed in CECT LR-3 and LR-4 hepatic lesions than in CEUS (7.3% vs. 19.5%, p < 0.001). The specificity and PPV of CEUS and CECT LR-5 for the diagnosis of HCC were 89.5%, 95.0%, and 82.5%, 94.4%, respectively. The sensitivity of CEUS LR-5 + LR-M for the diagnosis of hepatic malignancies was higher than that of CECT (93.7% vs. 82.7%, p < 0.001). The specificity and PPV of CEUS LR-M for the diagnosis of non-HCC malignancies were lower than those of CECT (59.7% vs. 95.5%, p < 0.001; 23.4% vs. 70.3%, p < 0.001)., Conclusions: The inter-modality consistency between the CEUS and CECT LI-RADS categories is fair. CEUS LI-RADS was more sensitive than CECT LI-RADS in terms of identifying hepatic malignancies, but weaker in terms of separating HCC from non-HCC malignancies., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Assessing the intake of sugar-sweetened beverages (SSBs) is crucial for reducing obesity; however, a simple but relatively accurate method for determining added sugar consumption among school adolescents is lacking. The aim of this study was to evaluate the reproducibility and validity of a food group-based food frequency questionnaire (FG-FFQ) for SSBs in assessing SSB consumption and added sugar among middle-school students. A total of 242 school students completed the FG-FFQs twice and four discontinuous 24-h dietary records (24HDR) over a three-month period. A weighted average approach was used to obtain the average sugar content in the sugary drink food group (FG). Correlation coefficient, weighted kappa statistic, misclassification analysis, and Bland-Altman plot were used to evaluate the validity and reproducibility of the FG-FFQ. Linear regression was utilized to obtain the calibration formulas. The average content of added sugar in sugary drink FG was 8.1 g/100 mL. SSB consumption frequency, consumption amount, and added sugar had correlation coefficients of 0.81, 0.87, and 0.87, respectively, in the validity analysis ( p < 0.05). The majority of scatter plots were covered by 95% confidence intervals in the Bland-Altman bias analysis. The intra-class correlation coefficient of SSB consumption frequency and Spearman correlation coefficient of SSB consumption amount and added sugar were 0.74, 0.81, and 0.90, respectively, in the reproducibility analysis ( p < 0.05). Results produced by the FG-FFQ calibration formula were more comparable to 24HDR. The FG-FFQ for SSB consumption showed acceptable validity and reproducibility, making it a viable instrument for epidemiological studies on sugary drinks in adolescents.

A nonionizing ultrafast laser pulse of 20-fs duration with a peak amplitude electric-field ±E = 200 × 10 -4 a.u. was simulated. It was applied to the ethene molecule to consider its effect on the electron dynamics, both during the application of the laser pulse and for up to 100 fs after the pulse was switched off. Four laser pulse frequencies ω = 0.2692, 0.2808, 0.2830, and 0.2900 a.u. were chosen to correspond to excitation energies mid-way between the (S 1 ,S 2 ), (S 2 ,S 3 ), (S 3 ,S 4 ) and (S 4 ,S 5 ) electronic states, respectively. Scalar quantum theory of atoms in molecules (QTAIM) was used to quantify the shifts of the C1C2 bond critical points (BCPs). Depending on the frequencies ω selected, the C1C2 BCP shifts were up to 5.8 times higher after the pulse was switched off compared with a static E-field with the same magnitude. Next generation QTAIM (NG-QTAIM) was used to visualize and quantify the directional chemical character. In particular, polarization effects and bond strengths, in the form of bond-rigidity vs. bond-flexibility, were found, for some laser pulse frequencies, to increase after the laser pulse was switched off. Our analysis demonstrates that NG-QTAIM, in partnership with ultrafast laser irradiation, is useful as a tool in the emerging field of ultrafast electron dynamics, which will be essential for the design, and control of molecular electronic devices., (© 2023 Wiley Periodicals LLC.)

In this study, the lignin was pre-modified using small-molecule nitrogen-containing compounds, and then the nitrogen-doped lignin-based carbon nanotubes (L-NCNTs) were fabricated by pyrolysis using the modified lignin as raw materials. The obtained L-NCNTs were multi-walled carbon nanotubes with diameters between 10 and 80 nm. The modification of lignin had an important effect on the nitrogen morphology of L-NCNTs, and promoted the high selectivity of pyridine-N in the L-NCNTs. Defects and pyridinic-N structure were conducive to boosting photothermal properties of the L-NCNTs. The photothermal conversion efficiency of the L-NCNTs after 808 nm laser irradiation for 5 min reached 58.8 %. The L-NCNTs can be used as photothermal agents in drug delivery system to achieve mild photothermal therapy, and it is basically non-toxic to normal cells, indicating good biocompatibility. This work provides new ideas for development of lignin-based high value-added products from biomass., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Ascorbic acid (AsA) is a crucial water-soluble antioxidant in strawberry fruit, but limited research is currently available on the identification and functional validation of key genes involved in AsA metabolism in strawberries. This study analyzed the FaMDHAR gene family identification, which includes 168 genes. Most of the products of these genes are predicted to exist in the chloroplast and cytoplasm. The promoter region is rich in cis-acting elements related to plant growth and development, stress and light response. Meanwhile, the key gene FaMDHAR50 that positively regulates AsA regeneration was identified through comparative transcriptome analysis of 'Benihoppe' strawberry (WT) and its natural mutant (MT) with high AsA content (83 mg/100 g FW). The transient overexpression experiment further showed that overexpression of FaMDHAR50 significantly enhanced the AsA content by 38% in strawberry fruit, with the upregulated expression of structural genes involved in AsA biosynthesis ( FaGalUR and FaGalLDH ) and recycling and degradation ( FaAPX , FaAO and FaDHAR ) compared with that of the control. Moreover, increased sugar (sucrose, glucose and fructose) contents and decreased firmness and citric acid contents were observed in the overexpressed fruit, which were accompanied by the upregulation of FaSNS , FaSPS , FaCEL1 and FaACL , as well as the downregulation of FaCS . Additionally, the content of pelargonidin 3-glucoside markedly decreased, while cyanidin chloride increased significantly. In summary, FaMDHAR50 is a key positive regulatory gene involved in AsA regeneration in strawberry fruit, which also plays an important role in the formation of fruit flavor, apperance and texture during strawberry fruit ripening.

Background: Hepatic lipid accumulation was a major promoter for the further development of non-alcoholic fatty liver disease (NAFLD) in type 2 diabetes (T2DM). mTOR/YY1 signaling pathway regulated many metabolic processes in different organs, and played an important role in hepatic lipid metabolism. Thus, targeting mTOR/YY1 signaling pathway might be a novel therapeutic strategy of T2DM-associated NALFD., Purpose: To investigate the effects and the mechanism of quercetin against T2DM-associated NAFLD., Study Design and Methods: The combine abilities of 24 flavonoid compounds with mTOR were detected by computer virtual screening (VS) and molecular modeling. mTOR/YY1 signaling pathway was examined in the liver of db/db mice, and high glucose (HG) and free fatty acid (FFA) co-cultured HepG2 cells. YY1 overexpression lentivirus vector and mTOR specific inhibitor rapamycin were used to further identify the indispensable role of mTOR/YY1 signaling pathway in quercetin's amelioration effect of hepatic lipid accumulation in vitro. Clinical studies, luciferase assay and chromatin immunoprecipitation (ChIP) assay were all carried out to investigate the potential mechanisms by which quercetin exerted its amelioration effect of hepatic lipid accumulation., Results: Quercetin had the strongest ability to combine with mTOR and could competitively occupy its binding pocked. Along with the alleviated hepatic injury by quercetin, mTOR/YY1 signaling pathway was down-regulated in vivo and in vitro. However, the alleviation effect of quercetin against hepatic lipid accumulation was inhibited by YY1 overexpression in vitro. Mechanistically, the down-regulated nuclear YY1 induced by quercetin directly bound to CYP7A1 promoter and activated its transcription, resulting in the restoration of cholesterol homeostasis via the conversion of cholesterol-to-bile acids (BAs)., Conclusion: The hepatoprotective effect of quercetin on T2DM-associated NAFLD was linked to the restoration of cholesterol homeostasis by the conversion of cholesterol-to-BAs via down-regulating mTOR/YY1 signaling pathway, leading to the increased CYP7A1 activity., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Citric acid is the primary organic acid that affects the taste of strawberry fruit. Glycolysis supplies key substrates for the tricarboxylic acid cycle (TCA cycle). However, little is known about the regulatory mechanisms of glycolytic genes on citric acid metabolism in strawberry fruits. In this study, the citric acid content of strawberry fruit displayed a trend of rising and decreasing from the initial red stage to the full red stage and then dark red stage. Thus, a difference in citric acid metabolic regulation was suspected during strawberry fruit development. In addition, overexpression of either cytoplasm glyceraldehyde-3-phosphate dehydrogenase (FxaC&#95;14g13400, namely FaGAPC2 ) or pyruvate kinase (FxaC&#95;15g00080, namely FaPKc2.2 ) inhibited strawberry fruit ripening and the accumulation of citric acid, leading to a range of maturity stages from partial red to full red stage. The combined transcriptome and metabolome analysis revealed that overexpression of FaGAPC2 and FaPKc2.2 significantly suppressed the expression of phosphoenolpyruvate carboxykinase (FxaC&#95;1g21491, namely FaPEPCK ) but enhanced the content of glutamine and aspartic acid. Meanwhile, the activities of PEPCK and glutamate decarboxylase (GAD) were inhibited, but the activities of glutamine synthase (GS) were increased in FaGAPC2/FaPKc2.2 -overexpressed fruit. Further, functional verification demonstrated that overexpression of FaPEPCK can promote strawberry fruit ripening, resulting in a range of maturity stage from full red to dark red stage, while the citric acid synthase (CS) activities and citric acid content were significantly decreased. Overall, this study revealed that FaGAPC2 / FaPKc2.2 and FaPEPCK perform an important role in reducing citric acid content in strawberry fruit, and FaGAPC2 / FaPKc2.2 mainly by promoting the GS degradation pathway and FaPEPCK mainly by inhibiting the CS synthesis pathway., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yang, Hou, Peng, Wang, Liu, Jiang, He, She, Zhao, Chen, Li, Zhang, Lin, Zhang, Wang, He, Wang, Tang and Luo.)

The plant U-box (PUB) proteins are a type of E3 ubiquitin ligases well known for their functions in response to various stresses. They are also related to fruit development and ripening. However, PUB members possess such roles that remain unclear in strawberry. In this study, 155 PUB genes were identified in octoploid strawberry and classified into four groups. Their promoters possessed a variety of cis -acting elements, most of which are associated with abiotic stresses, followed by phytohormones response and development. Protein-protein interaction analysis suggested that FaU-box members could interact with each other as well as other proteins involved in hormone signaling and stress resistance. Transcriptome-based and RT-qPCR expression analysis revealed the potential involvement of FaU-box genes in resistance to stresses and fruit ripening. Of these, FaU-box98 and FaU-box136 were positively while FaU-box52 was negatively related to strawberry ripening. FaU-box98 comprehensively participated in resistance of ABA, cold, and salt, while FaU-box83 and FaU-box136 were broadly associated with drought and salt stresses. FaU-box18 and FaU-box52 were ABA-specific; FaU-box3 was specific to salt stress. In addition, the functional analysis of a randomly selected FaU-box ( FaU-box127 ) showed that the transient overexpression of FaU-box127 promoted the ripening of strawberry fruit, along with significant changes in the expression levels of some ripening-related genes and the content of organic acid and soluble sugar. Overall, these findings provided comprehensive information about the FaU-box gene family and identified the potential FaU-box members participating in stress resistance and strawberry fruit ripening regulation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Jiang, Lin, Wang, Peng, Yang, Jiang, Hou, Liu, Li, Zhang, Zhang, Chen, Wang, He, Wang, Tang and Luo.)

The same people exhibit various adoption behaviors for the same information on various networks. Previous studies, however, did not examine the variety of adoption behaviors on multi-layer networks or take into consideration this phenomenon. Therefore, we refer to this phenomenon, which lacks systematic analysis and investigation, as behavioral adoption diversity on multi-layered networks. Meanwhile, individual adoption behaviors have LTI (local trend imitation) characteristics that help spread information. In order to study the diverse LTI behaviors on information propagation, a two-layer network model is presented. Following that, we provide two adoption threshold functions to describe diverse LTI behaviors. The crossover phenomena in the phase transition is shown to exist through theoretical derivation and experimental simulation. Specifically, the final spreading scale displays a second-order continuous phase transition when individuals exhibit active LTI behaviors, and, when individuals behave negatively, a first-order discontinuous phase transition can be noticed in the final spreading scale. Additionally, the propagation phenomena might be impacted by the degree distribution heterogeneity. Finally, there is a good agreement between the outcomes of our theoretical analysis and simulation.

Due to increasing population pressure and urbanization, as well as global climate change impacts, many coastal river deltas are experiencing increased exposure, vulnerability and risks linked to natural hazards. Mapping the vulnerability and risk profiles of deltas is critical for developing preparedness, mitigation and adaptation policies and strategies. Current vulnerability and risk assessments focus predominantly on social factors, and typically, do not systematically incorporate a social-ecological systems perspective, which can lead to incomplete assessments. We argue that ecosystem services, which link both ecosystem functions and human well-being, can be used to better characterize the mutual dependencies between society and the environment within risk assessment frameworks. Thus, building on existing vulnerability and risk assessment frameworks, we propose a revised indicator-based framework for social-ecological systems of coastal delta environments, supported by a list of ecosystem service indicators that were identified using a systematic literature review. This improved framework is an effective tool to address the vulnerability and risk in coastal deltas, enabling the assessment of multi-hazard risks to social-ecological systems within and across coastal deltas and allows more targeted development of management measures and policies aimed at reducing risks from natural hazards., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

In this study, microplastics (MPs) in urban rivers in the Chengdu eco-zone were systematically studied. Microscopic observations and Fourier-transform infrared spectroscopy were used to determine the microplastic (MP) types. The MPs abundance ranged from 20.92 items/L to 762.95 items/L in water and from 20.92 items/100 g dry weight to 58.57 items/100 g dry weight in sediment. In both the water sample and sediment samples, the dominant MPs morphologies were fibres, lumps, and fragments, and the size of MPs was predominantly distributed in the 50-500 μm rage. The primary polymers were polyethylene (PE), polypropylene (PP), polystyrene (PS), and polyethylene terephthalate (PET). Locations with large populations and large areas of woodland and construction land tended to exhibit higher concentrations of MPs. Additionally, compared to water samples, sediment exhibited a more reliable correlation fitting data, thus indicating that sediment was more stable in reflecting the presence of MPs in rivers. This study supplemented the gap in MPs pollution in urban rivers in Chengdu city and discussed the impact of land use and population on the distribution of MPs. Suggestions were provided to alleviate MPs pollution in urban rivers from the perspective of urban planning., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Three series of quinazoline derivatives (7a-j, 8a-o, 9a-l) were designed and synthesized as EGFR L858R/T790M inhibitors. Series 7a-j and 8a-o are urea and thiourea derivatives while category 9a-l contain the Michael receptor active warhead. Most of the compounds exhibited excellent anti-proliferative activity in vitro against several cancer cell lines, including non-small cell lung cancer (NSCLC) cell lines A549 and H1975, among which 14 compounds had strong antiproliferative activity against A549 and H1975 cancer cells. What's more, they also showed moderate to excellent kinase inhibitory activity against EGFR WT and EGFR L858R/T790M . 8o exhibited the best kinase inhibitory activity with IC 50 values of 0.8, 2.7 nM against EGFR WT and EGFR L858R/T790M , respectively. Moreover, AO single staining and Annexin V-FITC/PI staining results also indicated that both 8o and 9b significantly induced apoptosis in A549 cells. 8o arrested the cell cycle at S phase and 9b arrested the cell cycle at G1 phase., (Copyright © 2022 Elsevier Inc. All rights reserved.)

We used next-generation QTAIM (NG-QTAIM) to explain the cis -effect for two families of molecules: C 2 X 2 (X = H, F, Cl) and N 2 X 2 (X = H, F, Cl). We explained why the cis -effect is the exception rather than the rule. This was undertaken by tracking the motion of the bond critical point ( BCP ) of the stress tensor trajectories T σ ( s ) used to sample the U σ -space cis- and trans-characteristics. The T σ (s) were constructed by subjecting the C1-C2 BCP and N1-N2 BCP to torsions ± θ and summing all possible T σ (s) from the bonding environment. During this process, care was taken to fully account for multi-reference effects. We associated bond-bending and bond-twisting components of the T σ (s) with cis- and trans- characteristics, respectively, based on the relative ease of motion of the electronic charge density ρ ( r b ). Qualitative agreement is found with existing experimental data and predictions are made where experimental data is not available.

Background: The incidence of Type 2 diabetes mellitus (T2DM) combined with non-alcoholic fatty liver disease (NAFLD) has risen over the years. This comorbid condition significantly increases the probability of cirrhosis, liver cancer, and mortality compared to the disease alone. The multi-targeted, holistic treatment efficacy of traditional Chinese medicine (TCM) plays a vital role in the treatment of T2DM and NAFLD. Jiedu Tongluo Tiaogan Formula (JTTF), based on TCM theory, is widely used in clinical treatment, and its effectiveness in lowering glucose, regulating lipids, improving insulin resistance, and its pathways of action have been demonstrated in previous studies. However, the mechanism of this formula has not been investigated from a metabolomics perspective. Moreover, high-quality clinical studies on T2DM combined with NAFLD are lacking. Therefore, we aim to conduct a clinical trial to investigate the clinical efficacy, safety, and possible pathways of JTTF in the treatment of T2DM combined with NAFLD using metabolomics techniques. Methods: A total of 98 participants will be recruited to this clinical trial and randomly assigned to either a treatment group (JTTF + conventional basic treatment) or control group (conventional basic treatment) in a 1:1 ratio. Both groups will have received the same lifestyle interventions in the preceding 12 weeks. The primary outcome will be change in visceral fat area and total score on the TCM syndromes efficacy score scale. The secondary outcome will include changes in ultrasound steatosis grade, fibrosis 4 score (FIB-4), metabolic parameters, anthropometric parameters, visceral fat area. In addition, serum and urine samples collected at baseline and at the end of 12 weeks of treatment will be sequentially tested for untargeted and targeted metabolomics. Discussion: This study will evaluate the efficacy and safety of JTTF, as well as investigate the differential metabolites and possible mechanisms of JTTF treatment in T2DM combined with NAFLD. We hypothesize that patients will benefit from JTTF, which may provide strong evidence for the clinical use of JTTF in the treatment of T2DM and NAFLD, leading to the possibility of further mechanistic exploration. Clinical Trial Registration: This clinical trial has been registered in China Clinical Trial Registry (ChiCTR 2100051174)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xu, Piao, Qu, Liu, Peng, Li, Zhao, Li, Wu, Fan, Chen and Yang.)

Purpose: To explore the diagnostic performance and interreader agreement of CEUS LI-RADS in diagnosing ≤ 30 mm liver nodules with different experienced radiologists., Methods: Between January 2018 and October 2020, 244 patients at high-risk for HCC who underwent CEUS were enrolled. Two novice radiologists and two expert radiologists independently evaluated LI-RADS categories and main features. Kappa (κ) and Kendall's tests were employed to evaluate the interreader agreement of CEUS LI-RADS. The diagnostic performance was determined based on sensitivity, specificity, accuracy, PPV and NPV., Results: The interreader agreement for arterial phase hyperenhancement, late and mild washout, early washout, and rim hyperenhancement was moderate to almost perfect (κ, 0.44-0.93) among the different levels of radiologists. The interreader agreement for the LI-RADS categories was substantial to almost perfect (κ, 0.78-0.88). However, the interreader agreement for marked washout was fair to moderate (κ, 0.28-0.50). When CEUS LR-5 was used as a diagnostic criterion for HCC, there were no statistical differences in sensitivity, specificity, accuracy, PPV and NPV among the radiologists (p > 0.05), except for the differences between Reader 4 and the remaining three radiologists in terms of accuracy and sensitivity (p < 0.05)., Conclusion: CEUS LI-RADS has good diagnostic agreement for ≤ 30 mm liver nodules among experienced radiologists., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: To compare the sensitivity and specificity of identifying and evaluating the choroidal neovascularisation (CNV) in punctate inner choroidopathy (PIC) by optical coherence tomography angiography (OCTA) versus dye angiography., Methods: Consecutive patients diagnosed with PIC were enrolled in this study from June 2016 to December 2019. During the same visit, each patient underwent comprehensive ophthalmological and multimodal imaging examinations. The diagnostic accuracy of different modalities was evaluated., Results: The study included 160 affected eyes from 123 patients. Ninety-five eyes (59.38%) were identified with secondary CNV by multimodal imaging. The sensitivity and specificity for CNV detection with OCTA alone were 89.47% and 98.46%, respectively. OCTA also provided the morphology of CNV to determine the activity of CNV with a sensitivity of 86.67% and a specificity of 94.29%., Conclusions: In this study, we investigated the utility of OCTA in the diagnosis and evaluation of patients with CNV secondary to PIC. Compared with dye angiography, OCTA show convincing diagnosis accuracy. Although OCTA has several limitations and is not sufficient to replace dye angiography in clinical practice, it can provide clinicians with a non-invasive way to monitor patients with CNV secondary to PIC and guide treatment decisions., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Insulin-like growth factor-1 (IGF-1) and bone morphogenetic protein 2 (BMP-2) both promote osteogenesis of bone marrow mesenchymal stem cells (BMSCs). IGF-1C, the C domain peptide of IGF-1, and P24, a BMP-2-derived peptide, both have similar biological activities as their parent growth factors. This study aimed to investigate the effects and mechanisms of polypeptides IGF-1C and P24 on the osteogenic differentiation of BMSCs., Methods: The optimum concentrations of IGF-IC and P24 were explored. The effects of the two polypeptides on BMSC proliferation and osteogenic differentiation were examined using a CCK-8 assay, flow cytometry, alkaline phosphatase (ALP) staining, ALP activity assay, alizarin red S staining, qPCR, and Western blotting. In addition, specific pathway inhibitors were utilized to explore whether the p38 and JNK pathways were involved in this process., Results: The optimal concentration of both polypeptides was 50 μg/ml. IGF-1C and P24 synergistically promoted BMSC proliferation, increased ALP activity and calcified nodule formation, upregulated the mRNA and protein levels of Osx, Runx2, Ocn, Opn, and Col1a1, and improved the phosphorylation levels of p38 and JNK proteins. Inhibition of the pathways significantly reduced p38 and JNK activation and blocked Runx2 expression while inhibiting ALP activity and calcified nodule formation., Conclusions: These findings suggest that IGF-1C and P24 synergistically promote the osteogenesis of BMSCs through activation of the p38 and JNK signaling pathways., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Aims: Age-related macular degeneration (AMD) and high myopia are frequent causes of progressive visual impairment, so it is critical to identify animal models with resembling human retinal physiology, AMD and high myopia pathological features for therapeutic studies., Main Methods: We screened elderly cynomolgus monkeys for fundus lesions by slit-lamp biomicroscope combined with fundus pre-set lens and further examined positive cases by color fundus photography (CFP), optical coherence tomography (OCT), fundus fluorescein angiography (FFA), streak retinoscopy, and A-scan ultrasonography., Key Findings: Among the 156 animals examined, 10 males and 5 females (30 eyes) exhibited fundus abnormalities (9.6% prevalence). Multi-modal imaging revealed drusen in 20 eyes of 11 animals (prevalence rate of 7.1%), tessellated fundus in 22 eyes of 11 animals, and myopia choroidal neovascularization (CNV) in 4 eyes of 3 animals., Significance: Aged cynomolgus monkeys exhibit spontaneous fundus lesions resembling human AMD and high myopia, which could be an ideal model for clinical research., (Copyright © 2021. Published by Elsevier Inc.)

The evolution of local atomic configuration and macroscopic electrical properties of KNbO 3 is investigated in detail using ab initio molecular dynamics simulations within the framework of density functional theory. By analyzing the local off-center displacements of K and Nb atoms, the presence of the crossover of displacive and order-disorder mechanisms in the NbO 6 octahedron due to orbital hybridization is found, whereas the K is a completely displacive type due to the nonoriented ionic K-O bond. Besides, the order-disorder behavior of Nb atoms is enhanced with the increase in temperature, especially undergoing the phase transition. The predicted high dielectric constant of KNbO 3 confirms the key role of the Nb's order-disorder behavior. We discover that the anomalous increase in dielectric constant in the vicinity of the phase boundary is not only from the transformation of the polarized direction but also from the enhancement of order-disorder contribution in the nonpolarized direction. The high dielectric constant with large spontaneous polarization boosts the piezoelectricity at the orthorhombic-tetragonal phase boundary of 500 K, giving rise to the nearly 100% increase than that of 300 K. A rebonding model is developed to illustrate the origin of high piezoelectricity around the tetragonal ferroelectric phase boundary, and the significance of introducing a tetragonal structure is emphasized for developing high piezoelectricity in the inorganic perovskite ferroelectrics.

Angiogenesis in the field of tissue engineering has attracted significant attention. Graphene oxide has become a promising nanomaterial in tissue engineering for its unique biochemical properties. Therefore, herein, a series of chitosan (CS)/graphene oxide (GO) hydrogel scaffolds were synthesized by crosslinking CS and GO at different concentrations (0.1, 0.5, and 1.0 wt.%) using genipin. Compared with the CS hydrogel scaffolds, the CS/GO hydrogel scaffolds have a better network structure and mechanical strength. Then, we used endothelial progenitor cells (EPCs) extracted from human umbilical cord blood and cocultured these EPCs with the as-prepared scaffolds. The scaffolds with 0.1 and 0.5 wt.%GO showed no considerable cytotoxicity, could promote the proliferation of EPCs and tube formation, and upregulated the expressions of CD34, VEGF, MMP9, and SDF-1 in EPCs compared to the case of the scaffold with 1.0 wt.%GO. This study shows that the addition of graphene oxide improves the structure of chitosan hydrogel and enhances the proliferation activity and angiogenic capacity of EPCs., Competing Interests: The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2021 Lifang Zhang et al.)

Objective: To investigate the prevalence and affecting factors of laryngopharyngeal reflux disease（LPRD） in otolaryngology head and neck surgery in Chongqing,and to provide a basis for the clinical diagnosis and therapy of LPRD. Methods: Multi-center cross-sectional survey method and systematic sampling method were used to select patients at fifteen hospitals in Chongqing from August to November in 2019. Then reflux symptom index（RSI） was investigated. At the same time, the information of the relevant dietary habits, including smoking and drinking, spicy diet, high-fat diet, and satiety was collected. Moreover, the factors related to LRPD（gender, age, symptoms, diet and lifestyle） were analyzed. Results: The composition ratio of LPRD was 11.90%（385/3234） in 3234 effective questionnaires and 385 positive ones. The composition ratio was 12.55%（173/1378） in men and 11.42%（212/1856） in women. The difference between the two groups was statistically significant（ P <0.05）. The difference in composition ratio among different age groups was statistically significant（ P <0.05）, with the highest composition ratio between 40 and 59 years old（170/1390）. Constant throat-clearing（symptom 2） and globus sensation（symptom 8） were most correlated with LPRD. Logistic regression analysis showed that spicy diet, over eating, and smoking were highly related to LPRD. Conclusion: Globus sensation and constant throat-clearing are the most common symptoms in LPRD patients. Spicy diet, over eating, and smoking are risk factors for LPRD., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Background: Retina diseases may lead to blindness as they often afflict both eyes. Stem cell transplantation into the affected eye(s) is a promising therapeutic strategy for certain retinal diseases. Human peripheral blood mononuclear cells (hPBMCs) are a good source of stem cells, but it is unclear whether pre-induced hPBMCs can migrate from the injected eye to the contralateral eye for bilateral treatment. We examine the possibility of bilateral cell transplantation from unilateral cell injection., Methods: One hundred and sixty-one 3-month-old retinal degeneration 1 (rd1) mice were divided randomly into 3 groups: an untreated group (n = 45), a control group receiving serum-free Dulbecco's modified Eagle's medium (DMEM) injection into the right subretina (n = 45), and a treatment group receiving injection of pre-induced hPBMCs into the right subretina (n = 71). Both eyes were examined by full-field electroretinogram (ERG), immunofluorescence, flow cytometry, and quantitative real-time polymerase chain reaction (qRT-PCR) at 1 and 3 months post-injection., Results: At both 1 and 3 months post-injection, labeled pre-induced hPBMCs were observed in the retinal inner nuclear layer of the contralateral (left untreated) eye as well as the treated eye as evidenced by immunofluorescence staining for a human antigen. Flow cytometry of fluorescently label cells and qRT-PCR of hPBMCs genes confirmed that transplanted hPBMCs migrated from the treated to the contralateral untreated eye and remained viable for up to 3 months. Further, full-field ERG showed clear light-evoked a and b waves in both treated and untreated eyes at 3 months post-transplantation. Labeled pre-induced hPBMCs were also observed in the contralateral optic nerve but not in the blood circulation, suggesting migration via the optic chiasm., Conclusion: It may be possible to treat binocular eye diseases by unilateral stem cell injection.

Photocatalysis with stable, efficient and inexpensive metal-free catalysts is one of the most promising options for non-polluting energy production. This review article covers the state-of-the-art development of various effective metal-free polymeric photocatalysts with large π-conjugated units for chemical transformations including water splitting, CO2 and N2 reduction, organic synthesis and monomer polymerisation. The article starts with the catalytic mechanisms of metal-free photocatalysts. Then a particular focus is on the rational manipulation of π-conjugation enlargement, charge separation, electronic structures and band structures in the design of metal-free polymeric photocatalysts. Following the design principles, the selection and construction of functional units are discussed, as well as the connecting bonds and dimensions of π-conjugated polymeric photocatalysts. Finally the hot and emerging applications of metal-free polymeric photocatalysts for photocatalytic chemical transformations are summarized. The strategies provide potential avenues to address the challenges of catalyst activity, selectivity and stability in the further development of highly effective metal-free polymeric photocatalysts.

Background: Preoperative identification of hepatocellular carcinoma (HCC), combined hepatocellular-cholangiocarcinoma (cHCC-ICC), and intrahepatic cholangiocarcinoma (ICC) is essential for treatment decision making. We aimed to use ultrasound-based radiomics analysis to non-invasively distinguish histopathological subtypes of primary liver cancer (PLC) before surgery., Methods: We retrospectively analyzed ultrasound images of 668 PLC patients, comprising 531 HCC patients, 48 cHCC-ICC patients, and 89 ICC patients. The boundary of a tumor was manually determined on the largest imaging slice of the ultrasound medicine image by ITK-SNAP software (version 3.8.0), and then, the high-throughput radiomics features were extracted from the obtained region of interest (ROI) of the tumor. The combination of different dimension-reduction technologies and machine learning approaches was used to identify important features and develop the moderate radiomics model. The comprehensive ability of the radiomics model can be evaluated by the area under the receiver operating characteristic curve (AUC)., Results: After digitally processing tumor ultrasound images, 5,234 high-throughput radiomics features were obtained. We used the Spearman + least absolute shrinkage and selection operator (LASSO) regression method for feature selection and logistics regression for modeling to develop the HCC-vs-non-HCC radiomics model (composed of 16 features). The Spearman + statistical test + random forest methods were used for feature selection, and logistics regression was applied for modeling to develop the ICC-vs-cHCC-ICC radiomics model (composed of 19 features). The overall performance of the radiomics model in identifying different histopathological types of PLC was moderate, with AUC values of 0.854 (training cohort) and 0.775 (test cohort) in the HCC-vs-non-HCC radiomics model and 0.920 (training cohort) and 0.728 (test cohort) in the ICC-vs-cHCC-ICC radiomics model., Conclusion: Ultrasound-based radiomics models can help distinguish histopathological subtypes of PLC and provide effective clinical decision making for the accurate diagnosis and treatment of PLC., (Copyright © 2020 Peng, Lin, Wu, Wan, Zhao, Liang, Ma, Qin, Liu, Li, Wang, He and Yang.)

In the field of electronics, organocatalysts are in high demand for use in the synthesis of clean polymers using solar radiation rather than potentially contaminating metals. Combining theoretical design, simulation, and experiments, this work presents a novel, pyridine-diketopyrrolopyrrole ( P-DPP )-based metal-free visible-light organophotoredox catalyst ( P-DPP ). It is effective in the photocontrolled organocatalytic atom-transfer radical polymerization (O-ATRP) of methyl methacrylate (MMA) and styrene. The use of this catalyst and white light-emitting diode (LED) irradiation produces polymers with a cross-linked feature. In O-ATRP, the P-DPP catalyst has an oxidative quenching catalytic mechanism with an excited-state reductive potential of -1.8 V, fluorescence lifetime of 7.5 ns, and radical-cation oxidative potential of 0.45 V. Through molecular simulation, we found that the adjacent pyridine group is key to reducing the alkyl halide initiator and generating radicals, while the diketopyrrolopyrrole core stabilizes the triplet state of the catalyst through intramolecular charge transfer. The findings related to this novel photoredox catalyst will aid in the search for much more effective organophotoredox catalysts for use in controlled radical polymerization. They will also be of value in the fields of polymer chemistry and physics and in various applications.

In this work, the electronic and optical properties of one-dimensional (1D) Sb2S3 nanowires (NWs) with different sizes are investigated using first-principles calculations. The indirect-direct band transition of Sb2S3 NWs can be tuned effectively by the NW size and various uniaxial strains. In the Sb2S3 NWs, the quantum confinement effects result in wider bandgaps while the significantly enhanced electron-hole interaction that is expected to produce excitonic bound states generates a bandgap narrowing. The exciton binding energies for the Sb2S3 NWs are predicted by the effective masses of electrons and holes to lie in the range of 0-1 eV, which are larger than that of bulk Sb2S3, suggesting that excitons in Sb2S3 NWs may bind possible defects to promote luminescence. The size-controlled absorption edge blueshift and redshift of Sb2S3 NWs suggest that Sb2S3 NWs may be promising in the applications of nanoscale light emitting devices.

Importance: Chorodial structure in subtypes of polypoidal choroidal vasculopathy (PCV)., Background: To evaluate choroidal vascularity in the eyes of patients with PCV with and without choroidal vascular hyperpermeability (CVH)., Design: A hospital-based retrospective study., Participants: Fifty-eight PCV patients (28 with CVH; 30 without CVH) and 30 normal controls were included in this study., Methods: All study subjects underwent spectral-domain optical coherence tomography with enhanced depth imaging, and the choroidal images were binarized into the luminal area and stromal area., Main Outcome Measures: Choroidal vascularity index (CVI) and subfoveal choroidal thickness (SFCT)., Results: Compared to normal controls, patients with PCV showed no obvious difference in SFCT (P = 0.510), but significantly lower CVI (P = 0.003). Among PCV patients, the CVI in eyes with CVH was significantly greater than that in those without CVH (65.78 ± 4.70 vs 62.28 ± 3.90; P = 0.002), and a significant difference in SFCT was also found between the two subtypes of PCV (340.8 ± 89.2 vs 250.4 ± 67.7; P < 0.001)., Conclusions and Relevance: PCV eyes with CVH have a greater CVI and a thicker SFCT than those without CVH. The significant differences in choroidal vascularity between the two subtypes of PCV may broaden our understanding of the pathogenesis of this disease and contribute to significant improvements in treatment., (© 2019 Royal Australian and New Zealand College of Ophthalmologists.)

Purpose: To record the coexistence of polypoidal choroidal vasculopathy (PCV) with other rare fundus diseases in a Chinese population., Method: In this retrospective hospital-based study, a chart review of 861 patients with newly diagnosed PCV was performed. The clinical features of rare fundus comorbidities of PCV were recorded., Results: Five eyes of 5 patients aged 63.4 ± 11.22 years (0.58%) had PCV coexisting with other fundus diseases in the same eye. Of the 5 PCV patients, 2 (0.23%) had myelinated nerve fiber, 2 (0.23%) had branch retinal vein occlusion, and 1 (0.12%) had retinal angiomatous proliferation., Conclusion: We reported rare fundus comorbidities of PCV in a large Chinese cohort. These comorbidities included myelinated nerve fiber, branch retinal vein occlusion and retinal angiomatous proliferation. The combination might constitute an accidental occurrence.

Purpose: To investigate the etiologies and characteristics of choroidal neovascularization (CNV) in young Chinese patients., Methods: A retrospective review of young Chinese patients (< 50 years of age) with CNV from January 2010 to June 2016 was performed., Results: Of the 501 patients (537 eyes) with CNV, 58.7% were female, and 7.2% had bilateral CNV. The mean age was 35 years. The etiologies were idiopathic CNV (ICNV, 43.9%), pathologic myopia (PM, 21.9%), punctate inner choroidopathy (PIC, 17.4%), polypoidal choroidal vasculopathy (4.4%), multifocal choroiditis with panuveitis (3.6%), and other disorders (8.8%). Five hundred and six CNVs (94.2%) showed a predominantly classic CNV composition on fundus fluorescein angiography (FFA) and 316 CNVs (96.6%) were type 2 CNV on optical coherence tomography (OCT)., Conclusion: The etiologies of CNV in young Chinese patients were diverse, and ICNV, PM, and PIC were the three most common etiologies. Most CNVs were classic on FFA and type 2 on OCT., (© 2018 S. Karger AG, Basel.)

Purpose: To determine whether fluorescein leakage within subretinal hemorrhage is definitely suggestive of choroidal neovascularization (CNV) by multimodal imaging including optical coherence tomography angiography (OCTA)., Methods: Twenty-five consecutive highly myopic patients (25 eyes) with fluorescein leakage within subretinal hemorrhage detected within 1 month were prospectively included. All patients underwent OCTA and spectral-domain optical coherence tomography (SD-OCT). The OCTA and SD-OCT findings at the site of fluorescein leakage were analyzed. In cases of a doubtful diagnosis, indocyanine green angiography (ICGA) was also performed to differentiate myopic CNV from lacquer crack if necessary; all patients were followed up by SD-OCT and/or OCTA for at least 2 weeks., Results: In terms of the site of fluorescein leakage, OCTA revealed an abnormal vascular network in the outer retina and a choriocapillaris slab in 22 out of 25 eyes (88%), which were confirmed to be CNV. However, no high-flow signal was observed in 3 of 25 eyes (12%). In these 3 cases, SD-OCT showed a focal rupture of the retinal pigment epithelium-Bruch's membrane-choriocapillaris (RPE-BM-CC) complex and a columnar hyperreflective signal of blood originating from defects with a volcanic geyser-like appearance, and no exudative signs were detected. Notably, all ruptures of the RPE-BM-CC complex were located exactly at lacquer crack sites. Moreover, with the absorption of subretinal hemorrhage, ruptures of the RPE-BM-CC complex spontaneously resolved without any intervention. Considering the multimodal imaging appearance and follow-up outcomes, these 3 eyes were eventually diagnosed as simple bleeding associated with lacquer cracks., Conclusions: Dye leakage within recent subretinal hemorrhage on FA could be caused by new-onset lacquer cracks in pathologic myopia. Multimodal imaging including OCTA is helpful to differentiate lacquer cracks from myopic CNV.

Purpose: Whether sleep disturbance is related with central serous chorioretinopathy (CSC) is still in controversy. This study is designed to investigate sleep status in CSC using definite and well-established methods., Methods: A total of 134 CSC patients and 134 age- and sex-matched normal controls were recruited in the study. Demographic data were collected through a questionnaire. Body mass index (BMI) was calculated by weight divided by height squared. The Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) were administered to all subjects to assess the sleep quality and daytime sleepiness, respectively. Depression Anxiety Stress Scales 21-item version (DASS-21) was also used to evaluate the emotion status as a positive control. Poor sleep quality was defined as PSQI > 5 and sleep apnea tendency as ESS > 10. Positive criteria scores were ≥10 for depression, ≥8 for anxiety, and ≥15 for stress., Results: There was no significant difference of BMI between the two groups ( p =0.075). The prevalence of poor sleep quality (58.2% versus 23.9%; p < 0.001) in CSC patients was significantly higher than normal. Specifically, CSC patients presented worse performance in certain components of sleep quality, that is, sleep latency, sleep duration, and sleep efficiency. More participants had stress (23.9% versus 3%, p < 0.001), depression (25.4% versus 10.4%; p =0.001), and anxiety (28.4% versus 14.9%; p =0.008) emotions in CSC than that in normal. No significant difference was observed in sleep apnea tendency. Through logistic regression analysis, CSC patients were more likely to be in poor sleep quality ( p < 0.001; OR 3.608 (2.071-6.285)) and stress emotion ( p =0.002, OR 6.734 (1.997-22.711))., Conclusion: Poor sleep quality is risk factor for CSC patients. Attention of sleep quality should be paid when treating them.

Transition metal dichalcogenide (TMD) heterostructures have been widely explored due to the formation of type-II band alignment and interlayer exciton. However, the studies of type-I TMD heterostructures are still lacking, which limit their applications in luminescence devices. Here, the 1L/nL MX 2 (n = 2, 3, 4; M = Mo, W; X = S, Se) lateral homojunction based on the layer-dependent band gaps of TMD nanosheets is theoretically simulated. The studies show that the TMD homojunction presents with high thermal stability and type-I band alignment. The band offset and quantum confinement of carriers can be easily tuned by controlling the thickness of the multilayer region. Moreover, the electric field can decrease the band gaps of 1L/3L and 1L/4L homojunctions linearly. Interestingly, for the 1L/2L MX 2 homojunction, the gap value is robust to the weak electric field, while it drops sharply under a strong electric field. This study sheds light on the physical pictures in the TMD lateral homojunction, and provides a practicable and general approach to engineer a type-I homojunction based 2D semiconductor materials., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Introduction: To evaluate the functional and morphological outcomes of intravitreal conbercept monotherapy in patients with polypoidal choroidal vasculopathy (PCV)., Materials and Methods: In this retrospective, observational case series study, we reviewed medical records of 48 eyes (48 patients) with naive PCV that were treated with a series of 3 monthly intravitreal injections of 0.5 mg of conbercept followed by as-needed injections (3+pro re nata). All patients completed at least 6 months of monthly follow-up. Changes in the best-corrected visual acuity, optical coherence tomography, and indocyanine green angiography were retrospectively evaluated., Results: At 6 months, the mean best-corrected visual acuity significantly improved from 0.89±0.35 (20/160 in Snellen equivalent) at baseline to 0.58±0.26 (Snellen equivalent of 20/80; P <0.001), and 60.42% (29/48) of eyes had an improvement of three lines of vision; the mean central retinal thickness significantly decreased from 333.56±171.04 μm at baseline to 187.65±54.46 μm ( P <0.001), and 93.75% (45/48) achieved a dry macula. At 3 months, 6 of 32 eyes (18.75%) showed partial regression of branching vascular network, 14 of 32 (43.75%) patients showed complete resolution of polyps. The mean number of injections was 3.4±0.9 through 6 months. No conbercept-related systemic or ocular adverse effects were observed., Conclusion: Intravitreal injection of conbercept using "3+pro re nata" regimen significantly improved visual acuity and anatomical outcomes in treatment-naive patients with PCV., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Purpose: The aim of this study was to determine the association between nucleotide-binding and oligomerization domain (NOD)-like receptors (NLRs) family, pyrin domain-containing 3 (NLRP3) inflammasome-induced inflammation and disease severity in diabetic retinopathy (DR)., Methods: Blood samples were collected from 64 patients with diabetes (DR, 43; without DR, 21) and 25 healthy controls. The protein and mRNA expression levels of NLRP3 inflammasomes in peripheral blood mononuclear cells were determined using western blotting and quantitative real-time reverse transcription-PCR. A total of 82 vitreous samples were obtained from patients with DR (n = 60) and nondiabetic controls (n = 22). All patients were candidates for vitrectomy. Interleukin (IL)-1β and IL-18 in the peripheral blood mononuclear cell culture medium and vitreous fluid were detected by enzyme-linked immunosorbent assay (ELISA). Immunofluorescence staining for apoptosis-associated speck-like protein with a caspase recruitment domain (ASC) and NLRP3 was performed in fibrovascular membranes from 21 proliferative DR patients and 22 controls with idiopathic epiretinal membranes., Results: We observed increased gene and protein expression of NLRP3, ASC, and caspase-1 in peripheral blood mononuclear cells of adults with DR compared with that in normal controls. Furthermore, the elevated expressions of NLRP3 and ASC were observed in the fibrovascular membranes from 21 adults with proliferative DR when compared with the 22 controls. IL-1β and IL-18 in the peripheral blood mononuclear cells and vitreous fluid were elevated in the DR patients when compared with controls., Conclusions: These outcomes suggested that NLRP3 inflammasomes are upregulated in adults with DR and may play a key role in the pathogenesis and progression of DR.

Background: To evaluate the efficacy and safety of intravitreal conbercept (KH902) as the primary treatment of choroidal neovascularization secondary to punctate inner choroidopathy., Methods: This study was a retrospective, consecutive, observational case series. We reviewed medical records of 16 eyes (16 patients) with naive subfoveal or juxtafoveal choroidal neovascularization secondary to punctuate inner choroidopathy that were treated with intravitreal conbercept injections. All patients completed at least six months of follow-up. Best-corrected visual acuity (BCVA) was measured, and anatomical features were assessed with fluorescein angiography, indocyanine green angiography, and optical coherence tomography., Results: At the month-6 follow-up visit, best-corrected visual acuity improved from 0.70 ± 0.36 (with approximate Snellen equivalent of 20/100) to 0.44 ± 0.25 (20/50 in Snellen) logarithm of the minimum angle of resolution (logMAR) (P = 0.003). Mean improvement of vision was 2.6 lines, with 50% treated eyes (8 eyes of 16) showing an improvement of ≥3 lines and 62.5% (10 eyes of 16), obtaining an improvement of ≥2 lines; all 16 eyes had stable or improved vision. Mean central retinal thickness decreased from 294.94 ± 102.68 μm to 206.56 ± 61.71 μm (P = 0.005). Fifteen eyes (93.75%) showed absence of CNV leakage at the end of the study period. No conbercrept-related systemic or ocular adverse events were observed., Conclusion: Intravitreal injection of conbercept significantly improved visual and anatomical outcomes in choroidal neovascularization secondary to punctate inner choroidopathy over a 6-month follow-up period., Trial Registration: ISRCTN85678307 , retrospectively registered on May 11, 2017.