Eriodictyol regulates white adipose tissue browning and hepatic lipid metabolism in high fat diet-induced obesity mice via activating AMPK/SIRT1 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Blossom of Citrus aurantium L. var. amara Engl. (CAVA) has been popularly consumed as folk medicine and dietary supplement owing to its various beneficial effects and especially anti-obesity potential. Our previous study predicted that eriodictyol was probably one of the key active compounds of the total flavonoids from blossom of CAVA. However, effects of eriodictyol in anti-obesity were still elusive. AIM OF THE STUDY: This study was performed to explore the precise role of eriodictyol in white adipose tissue (WAT) browning and hepatic lipid metabolism, and simultaneously, to verify the impact of eriodictyol on the total flavonoids of CAVA in losing weight. MATERIALS AND METHODS: The pancreas lipase assay was conducted and oleic acid-induced HepG2 cells were established to preliminarily detect the lipid-lowering potential of eriodictyol. Then, high fat diet-induced obesity (DIO) mouse model was established for in vivo studies. The biochemical indicators of mice were tested by commercial kits. The histopathological changes of WAT and liver in mice were tested by H&E staining, Oil Red O staining and Sirius Red staining. Immunohistochemical, Western blot assay, as well as RT-qPCR analysis were further performed. Additionally, molecular docking assay was used to simulate the binding of eriodictyol with potential target proteins. RESULTS: In vitro studies showed that eriodictyol intervention potently inhibited pancreatic lipase activity and reversed hepatic steatosis in oleic acid-induced HepG2 cells. Consistently, long-term medication of eriodictyol also effectively prevented obesity and improved lipid and glucose metabolism in diet-induced obesity mice. Obesity-induced histopathological changes in iWAT, eWAT and BAT, and abnormal expression levels of IL-10, IL-6 and TNF-α in iWAT of DIO mice were also significantly reversed by eriodictyol treatment. Eriodictyol administration significantly and potently promoted browning of iWAT by increasing expression levels of thermogenic marker protein of UCP1, as well as brown adipocyte-specific genes of PGC-1α, SIRT1 and AMPKα1. Further assays revealed that eriodictyol enhanced mitochondrial function, as shown by an increase in compound IV activity and the expression of tricarboxylic acid cycle-related genes. Besides, eriodictyol addition markedly reversed hepatic damages and hepatic inflammation, and enhanced hepatic lipid metabolism in DIO mice, as evidenced by its regulation on p-ACC, CPT1-α, UCP1, PPARα, PGC-1α, SIRT1 and p-AMPKα expression. Molecular docking results further validated that AMPK/SIRT1 pathway was probably the underlying mechanisms by which eriodictyol acted. CONCLUSION: Eriodictyol exhibited significant anti-obesity effect, which was comparable to that of the total flavonoids from blossom of CAVA. These findings furnished theoretical basis for the application of eriodictyol in weight loss.

Efficient and Stable NIR-II Phosphorescence of Metallophilic Molecular Oligomers for In Vivo Single-Cell Tracking and Time-Resolved Imaging.

Molecular phosphorescence in the second near-infrared window (NIR-II, 1000-1700 nm) holds promise for deep-tissue optical imaging with high contrast by overcoming background fluorescence interference. However, achieving bright and stable NIR-II molecular phosphorescence suitable for biological applications remains a formidable challenge. Herein, we report a new series of symmetric isocyanorhodium(I) complexes that could form oligomers and exhibit bright, long-lived (7-8 µs) phosphorescence in aqueous solution via metallophilic interaction. Ligand substituents with enhanced dispersion attraction and electron-donating properties were explored to extend excitation/emission wavelengths and enhanced stability. Further binding the oligomers with fetal bovine serum (FBS) resulted in NIR-II molecular phosphorescence with high quantum yields (up to 3.93 %) and long-term stability in biological environments, enabling in vivo tracking of single-macrophage dynamics and high-contrast time-resolved imaging. These results pave the way for the development of highly-efficient NIR-II molecular phosphorescence for biomedical applications.

Antioxidant, Antimicrobial, and Anti-Inflammatory Effects of Liriodendron chinense Leaves.

Liriodendron chinense has been widely utilized in traditional Chinese medicine to treat dispelling wind and dampness and used for alleviating cough and diminishing inflammation. However, the antioxidant, antimicrobial, and anti-inflammatory effects of L. chinense leaves and the key active constituents remained elusive. So, we conducted some experiments to support the application of L. chinense in traditional Chinese medicine by investigating the antioxidant, antibacterial, and anti-inflammatory abilities, and to identify the potential key constituents responsible for the activities. The ethanol extract of L. chinense leaves (LCLE) was isolated and extracted, and assays measuring ferric reducing antioxidant power, total reducing power, DPPH•, ABTS•+, and •OH were used to assess its in vitro antioxidant capacities. Antimicrobial activities of LCLE were investigated by minimal inhibitory levels, minimum antibacterial concentrations, disc diffusion test, and scanning electron microscope examination. Further, in vivo experiments including macro indicators examination, histopathological examination, and biochemical parameters measurement were conducted to investigate the effects of LCLE on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. LCLE was further isolated and purified through column chromatography, and LPS-induced RAW264.7 cells were constructed to assess the diminished inflammation potential of the identified chemical composites. ABTS•+ and •OH radicals were extensively neutralized by the LCLE treatment. LCLE administration also presented broad-spectrum antimicrobial properties, especially against Staphylococcus epidermidis by disrupting cell walls. LPS-induced ALI in mice was significantly ameliorated by LCLE intervention, as evidenced by the histological changes in the lung and liver tissues as well as the reductions of nitric oxide (NO), TNF-α, and IL-6 production. Furthermore, three novel compounds including fragransin B2, liriodendritol, and rhamnocitrin were isolated, purified, and identified from LCLE. These three compounds exhibited differential regulation on NO accumulation and IL-10, IL-1ß, IL-6, TNF-α, COX-2, and iNOS mRNA expression in RAW264.7 cells induced by LPS. Fragransin B2 was more effective in inhibiting TNF-α mRNA expression, while rhamnocitrin was more powerful in inhibiting IL-6 mRNA expression. LCLE had significant antioxidant, antimicrobial, and anti-inflammatory effects. Fragransin B2, liriodendritol, and rhamnocitrin were probably key active constituents of LCLE, which might act synergistically to treat inflammatory-related disorders. This study provided a valuable view of the healing potential of L. chinense leaves in curing inflammatory diseases.

Brominated Quaternary Ammonium Salt-Assisted Hybrid Electron Transport Layer for High-Performance Conventional Organic Solar Cells.

Interlayer engineering is crucial for achieving efficient and stable organic solar cells (OSCs). Herein, by introducing a commercialized brominated quaternary ammonium salt, hexamethonium bromide (HB), into a perylene diimide (PDI)-structured electron transport layer (ETL), a PDINN:HB hybrid ETL with enhanced charge collection ability and environmental/operational stability is realized. Molecular dynamics simulations and Kelvin probe force microscopy indicate that strong polar bromine and amine groups can form extra interfacial dipoles in the hybrid interlayer, while X-ray photoelectron spectroscopy and electron paramagnetic resonance suggest the hybrid ETL can interact with the Ag cathode, thereby regulating the energy level arrangement at the interface. As for the results, the PDINN:HB hybrid ETL enables improved power conversion efficiency (PCE) from 17.8 to 18.4% and 18.8 to 19.4% in PM6:C5-16 bulk heterojunction- and PM6/L8-BO pseudobulk heterojunction-based OSCs, respectively. The versatility of this method is further verified by introducing a range of brominated quaternary ammonium salts into PDINN, in which a superior PCE and stability are all obtained compared to the reference device.

2X-Rhodamine: A Bright and Fluorogenic Scaffold for Developing Near-Infrared Chemigenetic Indicators.

Chemigenetic fusion of synthetic dyes with genetically encoded protein tags presents a promising avenue for in vivo imaging. However, its full potential has been hindered by the lack of bright and fluorogenic dyes operating in the "tissue transparency" near-infrared window (NIR, 700-1700 nm). Here, we report 2X-rhodamine (2XR), a novel bright scaffold that allows for the development of live-cell-compatible, NIR-excited variants with strong fluorogenicity beyond 1000 nm. 2XR utilizes a rigidified π-skeleton featuring dual atomic bridges and functions via a spiro-based fluorogenic mechanism. This design affords longer wavelengths, higher quantum yield (ΦF = 0.11), and enhanced fluorogenicity in water when compared to the phosphine oxide-cored, or sulfone-cored rhodamine, the NIR fluorogenic benchmarks currently used. We showcase their bright performance in video-rate dynamic imaging and targeted deep-tissue molecular imaging in vivo. Notably, we develop a 2XR variant, 2XR715-HTL, an NIR fluorogenic ligand for the HaloTag protein, enabling NIR genetically encoded calcium sensing and the first demonstration of in vivo chemigenetic labeling beyond 1000 nm. Our work expands the library of NIR fluorogenic tools, paving the way for in vivo imaging and sensing with the chemigenetic approach.

Ultra-photostable small-molecule dyes facilitate near-infrared biophotonics.

Long-wavelength, near-infrared small-molecule dyes are attractive in biophotonics. Conventionally, they rely on expanded aromatic structures for redshift, which comes at the cost of application performance such as photostability, cell permeability, and functionality. Here, we report a ground-state antiaromatic strategy and showcase the concise synthesis of 14 cationic aminofluorene dyes with mini structures (molecular weights: 299-504 Da) and distinct spectra covering 700-1600 nm. Aminofluorene dyes are cell-permeable and achieve rapid renal clearance via a simple 44 Da carboxylation. This accelerates optical diagnostics of renal injury by 50 min compared to existing macromolecular approaches. We develop a compact molecular sensing platform for in vivo intracellular sensing, and demonstrate the versatile applications of these dyes in multispectral fluorescence and optoacoustic imaging. We find that aromaticity reversal upon electronic excitation, as indicated by magnetic descriptors, not only reduces the energy bandgap but also induces strong vibronic coupling, resulting in ultrafast excited-state dynamics and unparalleled photostability. These results support the argument for ground-state antiaromaticity as a useful design rule of dye development, enabling performances essential for modern biophotonics.

Construction and application of a risk index of Echinococcus infection based on the classification of echinococcosis lesions / 中国血吸虫病防治杂志

Objective To investigate the feasibility of constructing the risk index of Echinococcus infection based on the classification of echinococcosis lesions, so as to provide insights into the management of echinococcosis. Methods The imaging data of echinococcosis cases were collected from epidemiological surveys of echinococcosis in China from 2012 to 2016, and the detection of incident echinococcosis cases was captured from the annual echinococcosis prevention and control reports across provinces (autonomous regions) and Xinjiang Production and Construction Corps in China from 2017 to 2022. After echinococcosis lesions were classified, a risk index of Echinococcus infection was constructed based on the principle of discrete distribution marginal probability and multi-group classification data tests. The correlation between the risk index of Echinococcus infection and the detection of incident echinococcosis cases was evaluated in the provinces (autonomous regions and corps) from 2017 to 2022, and the correlations between the short and medium-term risk indices and between the medium and long-term risk indices of Echinococcus infection were examined using a univariate linear regression model. Results A total of 4 014 echinococcosis cases in China from 2012 to 2016 were included in this study. The short-, medium- and long-term risk indices of E. granulosus infection varied in echinococcosis-endemic provinces (autonomous regions and corps) of China (χ2 = 4.12 to 708.65, all P values < 0.05), with high short- (0.058), medium- (0.137) and long-term risk indices (0.104) in Tibet Autonomous Region, and the short-, medium- and long-term risk indices of E. multilocularis infection varied in echinococcosis-endemic provinces (autonomous regions and corps) of China (χ2 = 6.74 to 122.60, all P values < 0.05), with a high short-term risk index in Sichuan Province (0.016) and high medium- (0.009) and long-term risk indices in Qinghai Province (0.018). There were no significant correlations between the risk index of E. granulosus infection and the detection of incident cystic echinococcosis cases during the study period (t = −0.518 to 2.265, all P values > 0.05), and strong correlations were found between the risk indices of E. multilocularis infection and the detection of incident alveolar echinococcosis cases (including mixed type) in 2018, 2020, 2021, 2022, during the period from 2017 through 2020, from 2017 through 2021, from 2017 through 2022 (all r values > 0.7, t = 2.521 to 3.692, all P values < 0.05). Linear regression models were established between the risk index of E. multilocular infection and the detection of alveolar echinococcosis cases (including mixed type), and the models were all statistically significant (b = 0.214 to 2.168, t = 2.458 to 3.692, F = 6.044 to 13.629, all P values < 0.05). The regression coefficients for the correlations between the medium- and short-term, and between the long- and medium-term risk indices of E. granulosus infection were 2.339 and 0.765, and the regression coefficients for the correlations between the medium- and short-term, and between the long- and medium-term risk indices of E. multilocular infection were 0.280 and 1.842, with statistical significance seen in both the regression coefficients and regression models (t = 16.479 to 197.304, F = 271.570 to 38 928.860, all P values < 0.05). Conclusions The risk index of Echinococcus infection has been successfully established based on the classification of echinococcosis lesions, which may provide insights into the prevention and control, prediction, diagnosis and treatment, and classified management of echinococcosis.

[Comparison of clinical effects of minimally invasive femoral head replacement and proximal femoral nail antirotation in the treatment of comminuted intertrochanteric fracture in the elderly].

OBJECTIVE: To analyze the clinical effect of minimally invasive femoral head replacement and proximal femoral nail antirotation(PFNA) internal fixation at the same time in the treatment of elderly patients with comminuted intertrochanteric fracture. METHODS: From April 2020 to October 2020, 76 elderly patients with comminuted intertrochanteric fracture treated by minimally invasive femoral head replacement and PFNA were analyzed retrospectively. There were 35 patients in the prosthetic group, including 24 females and 11 males with an average age of (86.2±6.1) years old. There were 41 patients in PFNA group including 28 females and 13 males with an average age of (84.6±5.3) years old. The operation time, intraoperative blood loss, postoperative ambulation time, hospitalization time and complications were observed and compared between two groups. Harris hip score was performed at 1, 6 and 12 months after operation. RESULTS: All patients were followed up for 13 to 17 months with an average of (14.3±1.4) months. The operation time of the prosthesis group was longer than that of the PFNA group (P<0.05);the amount of bleeding in PFNA group was less than that in prosthesis group (P>0.05);the time of ambulation in prosthetic group was earlier than that in PFNA group(P<0.05);the number of complications in the prosthesis group was less than that in the PFNA group(P<0.05); the Harris score of prosthesis group was significantly higher than that of PFNA group at 1 and 6 months after operation (P<0.05), but there was no significant difference in Harris score between two groups at 12 months after operation(P>0.05);the number of complications in the prosthesis group was less than that in the PFNA group (P<0.05). CONCLUSION: Minimally invasive femoral head replacement is a good choice for the elderly patients with commuited intertrochanteric fracture. It can improve the quality of life and reduce the burden of family members and society.

Tectorigenin alleviates the apoptosis and inflammation in spinal cord injury cell model through inhibiting insulin-like growth factor-binding protein 6.

Since tectorigenin has been reported to possess anti-inflammation, redox balance restoration, and anti-apoptosis properties, we determine to unravel whether tectorigenin has potential in alleviating spinal cord injury (SCI). Herein, PC12 cells were induced by lipopolysaccharide (LPS) to establish in vitro SCI models. The cell viability and apoptosis were detected through cell counting kit-8 and flow cytometry assays. The caspase-3/8/9 content was measured by colorimetric method. Western blot was conducted to quantify the expressions of cleaved caspse-3/8/9, IGFBP6, TLR4, IκBα, p-IκBα, RELA proto-oncogene, p65, and p-p65. Enzyme-linked immunosorbent assay and real-time quantitative polymerase chain reaction were carried out to quantitate expressions of IGFBP6, interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). SwissTargetPrediction and GSE21497 database were utilized to predict the potential therapeutic targets of tectorigenin. Comparison of IGFBP6 expression in SCI tissues and normal tissues was analyzed by GEO2R. Our study found that LPS induced the declined cell viability, elevated cell apoptosis, upregulation of caspase-3/8/9, cleaved caspase-3/8/9, IL-1ß, IL-6, TNF-α, IGFBP6, and TLR4, and the activation of IκBα and p65 in PC12 cells. Tectorigenin reversed the above effects of LPS. IGFBP6 was predicted to be the potential therapeutic target of tectorigenin and was overexpressed in SCI tissues. Notably, IGFBP6 overexpression offset the effects of tectorigenin on PC12 cells. In conclusion, tectorigenin could alleviate the LPS-induced apoptosis, inflammation, and activation of NF-κB signaling in SCI cell models via inhibiting IGFBP6.

Undescribed isoquinolines from Zanthoxylum nitidum and their antiproliferative effects against human cancer cell lines.

Eleven previously undescribed alkaloids, including three pairs of enantiomers nitidumalkaloids A-C, a pair of scalemic mixtures nitidumalkaloid D and three optically pure or achiral alkaloids, nitidumalkaloids E-G, along with 20 known alkaloids, were isolated from an ethanolic extract of the whole Zanthoxylum nitidum (Roxb.) DC plant. The chemical structures of the alkaloids were elucidated using a combination of comprehensive nuclear magnetic resonance (NMR) and high-resolution electro-spray ionization mass spectrometry (HR-ESI-MS) analyses. The configuration of the stereogenic centers of all undescribed compounds was precisely established based on single-crystal X-ray diffraction and electronic circular dichroism (ECD) calculations. Racemic mixtures of nitidumalkaloids A-D were purified, and their enantiomers were analyzed via chiral-phase high-performance liquid chromatography with electrochemical detection measurements (HPLC-ECD). Twelve compounds exhibited significant antiproliferative activities against a panel of cancer cell lines. Further studies were designed to investigate the underlying molecular mechanism of (1'S, 6R)-nitidumalkaloid B, which was the most active antiproliferative agent against human cancer A549 cells. G2/M cell cycle arrest, induction of apoptosis, and suppression of the Wnt/ß-catenin signaling pathway were in part associated with the antiproliferative activity of (1'S, 6R)-nitidumalkaloid B. Moreover, (1'S, 6R)-nitidumalkaloid B inhibited cell migration by downregulating the epithelial-mesenchymal transition process in A549 cells. These data suggest that the antiproliferation activity of (1'S, 6R)-nitidumalkaloid B was correlated with the stereoselectivity of the stereoisomers, and (1'S, 6R)-nitidumalkaloid B was prioritized as a potential leading compound for the management of aggressive human non-small-cell lung cancer (NSCLC) from natural products.

Clinicopathological features of patients with RET fusion-positive non-small cell lung cancer / 中华病理学杂志

Objective: To investigate the clinicopathological features, treatment and prognosis of patients with RET fusion positive non-small cell lung cancer (NSCLC). Methods: A total of 1 089 NSCLCs were retrieved at Affiliated Hospital of Jiangnan University from August 2018 to April 2020. In all cases, multiple gene fusion detection kits (fluorescent PCR method) were used to detect the gene status of RET, EGFR, ALK, ROS1, KRAS, BRAF and HER2; and immunohistochemical method was used to detect the expression of PD-L1 and mismatch repair related proteins. The correlation between RET-fusion and patients' age, gender, smoking history, tumor stage, grade, pathologic type, and PD-L1, mismatch repair related protein expression was analyzed. Results: There were 22 cases (2.02%) detected with RET fusion-positive in 1 089 NSCLC patients, in which 11 males and 11 females; and the median age was 63.5 years. There were 20 adenocarcinomas, including 11 acinar predominant adenocarcinoma (APA), five solid predominant adenocarcinoma (SPA) and four lepidic predominant adenocarcinoma (LPA); There were one case each of squamous cell carcinoma (non-keratinizing type) and sarcomatoid carcinoma (pleomorphic carcinoma). There were 6 and 16 patients with RET fusion-positive who were in stage Ⅰ-Ⅱ and Ⅲ-Ⅳ respectively, and 16 cases with lymph node metastasis, 11 cases with distant metastasis. Among RET fusion-positive cases, one was detected with HER2 co-mutation. The tumor proportion score of PD-L1≥1% in patients with RET fusion positive lung cancer was 54.5% (12/22). Defects in mismatch repair protein expression were not found in patients with RET fusion positive NSCLC. Four patients with RET fusions positive (two cases of APA and two cases of SPA) received pratinib-targeted therapy, and two showed benefits from this targeted therapy. Conclusions: The histological subtypes of RET fusions positive NSCLC are more likely to be APA or SPA. RET fusion-positive NSCLC patients are associated with advanced clinical stage, lymph node metastases, and they may benefit from targeted therapy with RET-specific inhibitors.

Comparison of clinical effects of minimally invasive femoral head replacement and proximal femoral nail antirotation in the treatment of comminuted intertrochanteric fracture in the elderly / 中国骨伤

OBJECTIVE@#To analyze the clinical effect of minimally invasive femoral head replacement and proximal femoral nail antirotation(PFNA) internal fixation at the same time in the treatment of elderly patients with comminuted intertrochanteric fracture.@*METHODS@#From April 2020 to October 2020, 76 elderly patients with comminuted intertrochanteric fracture treated by minimally invasive femoral head replacement and PFNA were analyzed retrospectively. There were 35 patients in the prosthetic group, including 24 females and 11 males with an average age of (86.2±6.1) years old. There were 41 patients in PFNA group including 28 females and 13 males with an average age of (84.6±5.3) years old. The operation time, intraoperative blood loss, postoperative ambulation time, hospitalization time and complications were observed and compared between two groups. Harris hip score was performed at 1, 6 and 12 months after operation.@*RESULTS@#All patients were followed up for 13 to 17 months with an average of (14.3±1.4) months. The operation time of the prosthesis group was longer than that of the PFNA group (P<0.05);the amount of bleeding in PFNA group was less than that in prosthesis group (P>0.05);the time of ambulation in prosthetic group was earlier than that in PFNA group(P<0.05);the number of complications in the prosthesis group was less than that in the PFNA group(P<0.05); the Harris score of prosthesis group was significantly higher than that of PFNA group at 1 and 6 months after operation (P<0.05), but there was no significant difference in Harris score between two groups at 12 months after operation(P>0.05);the number of complications in the prosthesis group was less than that in the PFNA group (P<0.05).@*CONCLUSION@#Minimally invasive femoral head replacement is a good choice for the elderly patients with commuited intertrochanteric fracture. It can improve the quality of life and reduce the burden of family members and society.

NIR-II Dyad-Doped Ratiometric Nanosensor with Enhanced Spectral Fidelity in Biological Media for In Vivo Biosensing.

Ratiometric fluorescence nanosensors provide quantitative biological information. However, spectral shift and distortion of ratiometric nanosensors in biological media often compromise sensing accuracy, limiting in vivo applications. Here, we develop a fluorescent dyad (aBOP-IR1110) in the second near-infrared (NIR-II) window by covalently linking an asymmetric aza-BODIPY with a ONOO--responsive meso-thiocyanine. The dyad encapsulated in the PEGylated nanomicelle largely improves spectral fidelity in serum culture by >9.4 times compared to that of its noncovalent counterpart. The increased molecular weights (>1480 Da) and hydrophobicity (LogP of 7.87-12.36) lock dyads inside the micelles, which act as the shield against the external environment. ONOO--altered intramolecular Förster resonance energy transfer (FRET) generates linear ratiometric response with better serum tolerance, enabling us to monitor the dynamics of oxidative stress in traumatic brain injury and evaluate therapeutic efficiency. The results show high correlation with in vitro triphenyltetrazolium chloride staining, suggesting the potential of NIR-II dyad-doped nanosensor for in vivo high-fidelity sensing applications.

Polymethine Molecular Platform for Ratiometric Fluorescent Probes in the Second near-Infrared Window.

Visualizing biomolecules such as enzymes in the deep tissue of living organisms via molecular ratiometric fluorescent probes in the second near-infrared window (NIR-II) with a built-in self-calibration function can provide reliable information about relevant pathophysiological processes directly but so far is not feasible due to the lack of a fluorescence modulation strategy in the NIR-II window. Here we present a molecular platform Py-2 by integrating the rhodamine 6G scaffold and polymethine. The maximal emission wavelength of Py-2 was 1010 nm and blue-shifted to 945 nm when its secondary amine was acylated. Based on Py-2, two molecular ratiometric NIR-II fluorescent probes, nitroreductase-responsive Rap-N and ROS-responsive Rap-R, were constructed and successfully demonstrated in vitro and in vivo. Overall, this report presents a unique approach to developing ratiometric NIR-II molecular probes for in vivo biosensing.

Comprehensive metabolomics analysis of key taste components in different varieties of table grapes.

Grapes are one of the world's largest fruit crops, which are rich in nutrients and taste. Summer Black, Gui Fei, Kyoho Grape, Giant Rose, Shine Muscat, and Rosario Bianco are the six most popular table grapes in Wuxi city, Jiangsu province. Owing to the lack of comprehensive investigations of metabolites in table grapes, the metabolic causes of differences in their taste are unknown. In this study, metabolites of six table grapes were profiled using ultra-high-performance liquid chromatography-Q-Exactive Orbitrap tandem mass spectrometry combined with multivariate analysis. Orthogonal partial least squares discriminant analysis discriminated among the metabolites of these varieties. Metabolic pathway analysis revealed that carbohydrate and amino acid metabolisms were highly conserved among these varieties. Our results suggest that the taste differences in the six table grape varieties can be explained by variations in composition and abundance of carbohydrates, organic acids, amino acids, and polyphenols. This study provides comprehensive insights into the underlying metabolic causes of taste variation in table grapes.

Natural bioactive constituents from herbs and nutraceuticals promote browning of white adipose tissue.

Obesity is a significant public health problem worldwide that is characterized by abnormal or excessive fat accumulation. Unfortunately, the application of available weight-loss drugs has been restricted because of their serious adverse effects. Browning of white adipose tissue (WAT), which refers to the transformation of white adipocytes to beige adipocytes under certain stimulations, is regarded as a new strategy to solve the obesity problem. Numerous studies have recently evidenced that traditional Chinese medicine (TCM) could promote browning of WAT with multi-component and multi-target characteristics. This article summarizes natural constituents from TCM with stimulatory effects on browning of WAT in the past two decades. The active ingredients can be generally divided into polyphenols, saponins, alkaloids, terpenoids, phenylpropanoids and others, such as resveratrol, quercetin, curcumin, genistein, capsaicin, epigallocatechin gallate (EGCG), berberine, menthol, emodin and ginsenosides. Simultaneously, the chemical structures, source, model, efficacy and mechanism of these monomeric compounds are also described. And the mechanisms of these active ingredients are mainly involved in the regulation of PRDM16, PGC-1α, PPARγ, SIRT1, AMPK, ß3-adrenergic receptors, TRPV1 and TRPM8 channels, FGF21 and miRNAs. The present article opens opportunities for developing novel drugs or supplements from TCM with wide acceptability to prevent obesity progression and its associated metabolic disorders.

Counterion-Paired Bright Heptamethine Fluorophores with NIR-II Excitation and Emission Enable Multiplexed Biomedical Imaging.

Photon excitation and emission at the NIR-II spectral window enable high-contrast deep-tissue bioimaging. However, multiplexed imaging with NIR-II excitation and emission has been hampered by the limited chemical strategies to develop bright fluorophores with tunable absorption in this spectral regime. Herein, we developed a series of heptamethine cyanines (HCs) with varied absorption/emission maxima spanning from 1100 to 1600 nm through a physical organic approach. A bulky counterion paired to HCs was found to elicit substantial improvements in absorptivity (7-fold), brightness (14-fold), and spectral profiles in water, addressing a notorious quenching problem of NIR-II cyanines due to aggregation and polarization. We demonstrated the utilities of HC1222 and HC1342 for high-contrast dual-color imaging of circulatory system, lymphatic structures, tumor, and organ function in living mice under 1120 nm and 1319 nm excitation, showing HCs as a promising platform for non-invasive bioimaging.

Palaeoecology of Cambrian-Ordovician acritarchs from China: evidence for a progressive invasion of the marine habitats.

Palaeozoic acritarchs mostly represent organic-walled cysts of marine phytoplankton, and therefore, as primary producers, played an important role in the evolution of marine ecosystems. In this study, we use a selection of the most abundant acritarch taxa from the Cambrian and Ordovician of China to understand the evolution of the palaeoecological patterns of the phytoplankton over the period. The taxa are attributed to 40 easily distinguishable morphotypes, of which the precise palaeoenvironmental distribution from 60 localities is available. By placing the 40 morphotypes on inshore-offshore transects it can be concluded that acritarch microfloras were limited to inshore environments during the early Cambrian, and progressively extended from inshore environments to offshore marine habitats during the later parts of the Cambrian and towards the Early Ordovician, with a prominent shift near the Cambrian-Ordovician boundary, confirming the onset of the 'Ordovician plankton revolution'. In addition, the acritarch morphotypes evolved from low-diversity assemblages in the early Cambrian, dominated by simple spherical forms with limited ornamentation and simple process structures, to highly diverse assemblages with very complex morphologies in the Early and Middle Ordovician. During the Ordovician, the complex acritarch assemblages occupied most marine habitats, with palaeoecological distribution patterns similar to modern dinoflagellates. This article is part of the theme issue 'The impact of Chinese palaeontology on evolutionary research'.

NIR-II cell endocytosis-activated fluorescent probes for in vivo high-contrast bioimaging diagnostics.

Fluorescence probes have great potential to empower bioimaging, precision clinical diagnostics and surgery. However, current probes are limited to in vivo high-contrast diagnostics, due to the substantial background interference from tissue scattering and nonspecific activation in blood and normal tissues. Here, we developed a kind of cell endocytosis-activated fluorescence (CEAF) probe, which consists of a hydrophilic polymer unit and an acid pH-sensitive small-molecule fluorescent moiety that operates in the "tissue-transparent" second near-infrared (NIR-II) window. The CEAF probe stably presents in the form of quenched nanoaggregates in water and blood, and can be selectively activated and retained in lysosomes through cell endocytosis, driven by a synergetic mechanism of disaggregation and protonation. In vivo imaging of tumor and inflammation with a passive-targeting and affinity-tagged CEAF probe, respectively, yields highly specific signals with target-to-background ratios over 15 and prolonged observation time up to 35 hours, enabling positive implications for surgical, diagnostic and fundamental biomedical studies.

The neurotrophic and antineuroinflammatory effects of phenylpropanoids from Zanthoxylum nitidum var. tomentosum (Rutaceae).

Three novel lignans (1, 5 and 6) and two novel quinic acids (16 and 17) along with 15 known phenylpropanoids were obtained from the ethanol extract of Zanthoxylum nitidum var. tomentosum (Rutaceae). Their structures were confirmed by comprehensive spectroscopic data (NMR and HRESIMS), and the absolute configurations of all novel compounds were elucidated based on electronic circular dichroism (ECD) spectroscopic data. The production of nitric oxide (NO) in BV-2 microglial cells induced through lipopolysaccharide (LPS) was used to evaluate in vitro anti-neuroinflammatory activity of compounds 1-20. Compound 2, 3, 7 and 16 showed excellent inhibition of LPS-induced NO production. The structure-activity relationships of the isolates were investigated. In addition, the mechanism of action of 2 was elucidated by RT-PCR and Western blotting analysis, which indicated that it reduced neuroinflammatory mainly through NLRP3/caspase1 signaling pathways in LPS-induced BV2 microglial cells.