Artemyriantholides A-K, guaiane-type sesquiterpenoid dimers from Artemisia myriantha var. pleiocephala and their antihepatoma activity.

Artemyriantholides A-K (1-11) as well as 14 known compounds (12-25) were isolated from Artemisia myriantha var. pleiocephala (Asteraceae). The structures and absolute configuration of compounds 2 and 8-9 were confirmed by the single crystal X-ray diffraction analyses, and the others were elucidated by MS, NMR spectral data and electronic circular dichroism calculations. All compounds were chemically characterized as guaiane-type sesquiterpenoid dimers (GSDs). Compound 1 was the first example of the GSD fused via C-3/C-11' and C-5/C-13' linkages, and compounds 2 and 5 were rare GSDs containing chlorine atoms. Eleven compounds showed obvious inhibitory activity in HepG2, Huh7 and SK-Hep-1 cell lines by antihepatoma assay to provide the IC50 values ranging from 7.9 to 67.1 µM. Importantly, compounds 5 and 8 exhibited the best inhibitory activity with IC50 values of 14.2 and 18.8 (HepG2), 9.0 and 11.5 (Huh7), and 8.8 and 11.3 µM (SK-Hep-1), respectively. The target of compound 5 was predicted to be MAP2K2 by a computational prediction model. The interaction between compound 5 and MAP2K2 was conducted to give docking score of -9.0 kcal/mol by molecular docking and provide KD value of 43.7 µM by Surface Plasmon Resonance assay.

Ferroptosis inducers: A new frontier in cancer therapy.

Ferroptosis represents a non-apoptotic form of programmed cell death characterized by iron-dependent lipid peroxidation. This cell death modality not only facilitates the direct elimination of cancer cells, but also enhances their susceptibility to other pharmacological anti-cancer agents. The burgeoning interest in ferroptosis has been driven by a growing body of evidence that underscores the efficiency and minimal toxicity of ferroptosis inducers. Traditional inducers, such as erastin and RSL3 have shown substantial promise in clinical applications due to their potent therapeutic effects. Their significant potential of these inducers has spurred the development of a variety of small molecule ferroptosis inducers. These novel inducers boast an enhanced structural variety, improved metabolic stability, the capability to initiate ferroptosis without triggering apoptosis, making them well-suited for in vivo use. Despite these advancements, challenges still remain, particularly concerning the drug delivery, tumor specificity, and circulation duration of these small molecules in vivo. Addressing these challenges, contemporary research has pivoted towards innovative delivery systems tailored for ferroptosis inducers to facilitate precise, targeted, and synegestic therapeutic delivery. This review scrutinizes the latest progress in small molecule ferroptosis inducers and nano drug delivery systems geared towards ferroptosis sensitization. Furthermore, it delineated the prospective therapeutic advantages and the existing hurdles in the development of ferroptosis inducers for malignant tumor treatment.

Efficacy of polyethylene glycol loxenatide for type 2 diabetes mellitus patients: a systematic review and meta-analysis.

Objective: Some studies have proved that polyethylene glycol loxenatide (PEG-Loxe) has significant effects on controlling blood glucose and body weight in patients with type 2 diabetes mellitus (T2DM), but there is still some controversy over the improvement of blood lipid profiles (BLP) and blood pressure (BP), and more evidences are needed to verify such effects. Therefore, this study was conducted to provide a comprehensive evaluation of the efficacy of PEG-Loxe in improving blood glucose (BG), BLP, BP, body mass index (BMI), and body weight (BW) in patients with T2DM for clinical reference. Methods: Randomized controlled trials (RCT) in which PEG-Loxe was applied to treat T2DM were retrieved by searching PubMed, Cochrane Library, Embase, Medline, Scopus, Web of Science, China National Knowledge Infrastructure, China Scientific Journal, Wanfang Data, and SinoMed databases. Outcome measures included BG, BLP, BP, BMI, and BW. RevMan 5.3 software was used to perform data analysis. Results: Eighteen trials were identified involving 2,166 patients. In experimental group 1,260 patients received PEG-Loxe alone or with other hypoglycemic agents, while in control group 906 patients received placebo or other hypoglycemic agents. In the overall analysis, PEG-Loxe significantly reduced the levels of glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG), 2-h postprandial blood glucose (2-h PBG), BMI, and BW compared with control group. However, it had no obvious effect on total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), and diastolic blood pressure (DBP). Conclusion: PEG-Loxe has better hypoglycemic effects compared with placebo in patients with T2DM, but could not significantly improved TG, LDL-C, HDL-C, SBP, and DBP. And the combination of conventional hypoglycemic drugs (CHD) and PEG-Loxe could more effectively improve the levels of HbA1c, FPG, 2-h PBG, TC, TG, BMI, and BW compared with CHD in T2DM patients. Systematic Review Registration: www.inplasy.com, identifier INPLASY202350106.

Synthesis and antihepatoma activity of guaianolide dimers derived from lavandiolide I.

Guaianolide dimers represent a unique class of natural products with anticancer activities, but their low content in plants has limited in-depth pharmacological studies. Lavandiolide I is a guaianolide dimer isolated from Artemisia species, and had been synthesized on a ten-gram scale in four steps with 60 % overall yield, which showed potent antihepatoma activity on the HepG2, Huh7, and SK-Hep-1 cell lines with IC50 values of 12.1, 18.4, and 17.6 µM, respectively. To explore more active dimers, 33 lavandiolide I derivatives were designed, synthesized, and evaluated for their inhibitory activity on human hepatoma cell lines. Among them, 10 derivatives were more active than lavandiolide I and sorafenib on the three cell lines. The primary structure-activity relationship concluded that the introduction of aldehyde, ester, azide, amide, carbamate and urea functional groups at C-14' of the guaianolide dimer significantly enhanced the antihepatoma activity. Among these compounds, derivatives 25, 27, and 33 enhanced antihepatoma activity more than 1.2-5.8 folds than that of lavandiolide I, and demonstrated low toxicity to the human liver cell lines (THLE-2) and good safety profiles with selective index ranging from 1.3 to 3.4, while lavandiolide I was more toxic to THLE-2 cells. This work provides new insights into enhancing the antihepatoma efficacy and reducing the toxicity of sesquiterpenoid dimers.

Trajectories and comorbid symptom networks of posttraumatic stress symptoms in frontline rescuers: A longitudinal study.

BACKGROUND: Previous research has largely lacked studies that explore the trajectories of Posttraumatic stress symptoms (PTSS) and the structure of comorbid psychiatric symptom networks following traumatic event, while controlling for the severity of traumatic exposure. The present study aims to explore the characteristic trajectories of PTSS, in the context of ensuring controlled levels of traumatic exposure. Furthermore, the PTSS, depressive, and anxiety comorbid symptom networks of different PTSS trajectory subgroups are also investigated. METHODS: A total of 296 frontline rescue personnel were enrolled into our study. In an effort to control for variations in traumatic exposure severity, this study ensured that all participants had same responsibilities and cumulative operational duration at the post-disaster rescue circumstance. Growth mixture models (GMMs) were employed to scrutinize the trajectories of PTSS. Additionally, network analysis was used to examine the comorbid symptom network of PTSS, depression, and anxiety. RESULTS: Four distinct PTSS trajectories were identified, namely Persisting Symptom, Gradual Recovery, Gradual Aggravation, and Asymptomatic. Although both the Persisting Symptom and Gradual Aggravation groups belong to the high-risk subgroups for persistent PTSS, they exhibit differences in core symptoms within their respective networks. The core symptom for the Persisting Symptom Network is flashbacks, while for the Gradual Aggravation Network, it is sleep disturbances. CONCLUSION: To the best of our knowledge, the present study represents the first research endeavor to integrate longitudinal trajectory analysis of PTSS with longitudinal symptom network analysis, clarifying the evolving features of PTSS but also offering valuable insights for early screening and intervention strategies.

Nighttime warming and nitrogen addition effects on the microclimate of a freshwater wetland dominated by Phragmites australis.

The critical impacts of microclimate on carbon (C) cycling have been widely reported. However, the potential effects of global change on wetland microclimate remain unclear, primarily because of the absence of field manipulative experiment in inundated wetland. This study was designed to examine the effects of nighttime warming and nitrogen (N) addition on air, water, and sediment temperature and also reveal the controlling factors in a Phragmites australis dominated freshwater wetland on the North China Plain. Nighttime warming increased daily air, water, and sediment temperature by 0.24 °C, 0.27 °C, and 0.36 °C, respectively. The diurnal temperature range of water was decreased by 0.44 °C under nighttime warming, whereas warming had no effect on diurnal temperature range of air and sediment. In addition, N addition caused a reduction of 0.20 °C and 0.14 °C in daily water and sediment temperature by increasing vegetation coverage. There was a significant interaction between nighttime warming and N addition on water temperature. Furthermore, the vapor pressure deficit is the main factor affecting the extent of the warming-induced increases in air temperature. The changes of height and leaf area index of Phragmites australis are responsible for the cooling effects in the N addition plots. This study provides empirical evidence for the positive climate warming - microclimate feedback in freshwater wetland. However, N deposition leads to decreased water and sediment temperature. Our findings highlight the importance of incorporating the differential impacts of nighttime warming and N addition on air, water, and sediment temperature into the predictions of wetland C cycling responses to climate change.

Investigation the mechanism of iron overload-induced colonic inflammation following ferric citrate exposure.

Iron overload occurs due to excessive iron intake compared to the body's demand, leading to iron deposition and impairment of multiple organ functions. Our previous study demonstrated that chronic oral administration of ferric citrate (FC) caused colonic inflammatory injury. However, the precise mechanism underlying this inflammatory response remains unclear. The current study aims to investigate the mechanism by which iron overload induced by FC exposure leads to colonic inflammation. To accomplish this, mice were orally exposed to three different concentrations of FC (71 mg/kg/bw (L), 143 mg/kg/bw (M) and 286 mg/kg/bw (H)) for continuous 16 weeks, with the control group receiving ultrapure water (C). Exposure to FC caused disturbances in the excretory system, altered colonic flora alpha diversity, and enriched pathogenic bacteria, such as Mucispirillum, Helicobacter, Desulfovibrio, and Shigella. These changes led to structural disorders of the colonic flora and an inflammatory response phenotype characterized by inflammatory cells infiltration, atrophy of intestinal glands, and irregular thickening of the intestinal wall. Mechanistic studies revealed that FC-exposure activated the NF-κB signaling pathway by up-regulating TLR4, MyD88, and NF-κB mRNA levels and protein expression. This activation resulted in increased production of pro-inflammatory cytokines, further contributing to the colonic inflammation. Additionally, in vitro experiments in SW480 cells confirmed the activation of NF-κB signaling pathway by FC exposure, consistent with the in vivo findings. The significance of this study lies in its elucidation of the mechanism by which iron overload caused by FC exposure leads to colonic inflammation. By identifying the role of pathogenic bacteria and the NF-κB signaling pathway, this study could potentially offer a crucial theoretical foundation for the research on iron overload, as well as provide valuable insights for clinical iron supplementation.

Stereoconvergent and Chemoenzymatic Synthesis of Tumor-Associated Glycolipid Disialosyl Globopentaosylceramide for Probing the Binding Affinity of Siglec-7.

Disialosyl globopentaosylceramide (DSGb5) is a tumor-associated complex glycosphingolipid. However, the accessibility of structurally well-defined DSGb5 for precise biological functional studies remains challenging. Herein, we describe the first total synthesis of DSGb5 glycolipid by an efficient chemoenzymatic approach. A Gb5 pentasaccharide-sphingosine was chemically synthesized by a convergent and stereocontrolled [2 + 3] method using an oxazoline disaccharide donor to exclusively form ß-anomeric linkage. After investigating the substrate specificity of different sialyltransferases, regio- and stereoselective installment of two sialic acids was achieved by two sequential enzyme-catalyzed reactions using α2,3-sialyltransferase Cst-I and α2,6-sialyltransferase ST6GalNAc5. A unique aspect of the approach is that methyl-ß-cyclodextrin-assisted enzymatic α2,6-sialylation of glycolipid substrate enables installment of the challenging internal α2,6-linked sialoside to synthesize DSGb5 glycosphingolipid. Surface plasmon resonance studies indicate that DSGb5 glycolipid exhibits better binding affinity for Siglec-7 than the oligosaccharide moiety of DSGb5. The binding results suggest that the ceramide moiety of DSGb5 facilitates its binding by presenting multivalent interactions of glycan epitope for the recognition of Siglec-7.

Design, Preparation, and Mechanical Property Study of Polylactic Acid/Ca2BO3Cl: Eu2+, Dy3+ Composite Material for 3D Printing.

To break through the simplification of three-dimensional printing (3DP) materials and realize the application of long-persistent phosphors in more fields, polylactic acid doped with Ca2BO3Cl: Eu2+, Dy3+ was prepared in this study. The structure of the mixtures was analyzed and determined by infrared spectroscopy. The luminescence properties of phosphors and the composites were studied by fluorescence spectra and afterglow decay curve measurements. The yellow light of the mixtures could be attributed to the 5d-4f energy level transition of Eu2+. After the excitation of 254 nm ultraviolet lamp, the luminance and duration of the composites could be clearly observed. The mechanical properties of the composite filaments were tested, including maximal force and elasticity modulus. In particular, the influence of humidity on mechanical properties was analyzed in detail. The prepared composite filaments were printed into hollow dodecahedrons and presented in this study. Therefore, the composites had great properties and might be expected to put into practical applications of 3DP technology.

Changes in the characteristic volatile aromatic compounds in tuna cooking liquid during fermentation and deodorization by Lactobacillus plantarum RP26 and Cyberlindnera fabianii JGM9-1.

Tuna cooking liquid has unpleasant aroma. In our previous studies, Cyberlindnera fabianii JGM9-1 and Lactobacillus plantarum RP26 demonstrated the ability to degrade this unpleasant aroma. However, the mechanism of microbial deodorization remains unclear. In this study, tuna cooking liquid was fermented using JGM9-1 alone, RP26 alone, and a combination of both strains. Changes in volatile aromatic compounds during fermentation were analyzed using HS-SPME-GC/MS. The unpleasant aroma of tuna cooking liquid were nine characteristic aromatic compounds associated with fishy, stinky, and greasy aromas. Furthermore, we found that the fermentation of microbes removed these unpleasant aromatic compounds and replaced them with pleasant aromatic compounds that contributed to fruity, grassy, and floral aromas. Finally, we screened 21 strong pairwise correlations between the production and consumption of characteristic volatile aromatic compounds by RP26 and JGM9-1, through HCA, VIP, OAV and Spearman's pairwise correlation analysis. These results help to clarify the metabolic mechanisms of microbial deodorization in tuna cooking liquid.

The association between lipid parameters and erectile dysfunction: a two-sample Mendelian randomization and case-control study.

PURPOSE: Lipid parameters have been shown to have significant predictive value for cardiovascular disease, but few studies have evaluated their correlation with erectile dysfunction (ED) in young men. METHODS: The case-control study encompassed 186 young ED patients (ages 20-40) and 186 healthy controls. Lipid parameters, including total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), TC/HDL ratio, TG/HDL ratio, and LDL-C/HDL-C ratio, were assessed in all participants. The International Index of Erectile Function (IIEF-5) scores were collected for all participants to evaluate erectile status. Multivariate logistic regression analysis was utilized to appraise the association of lipid-related parameters with ED. Single-nucleotide polymorphisms (SNPs) significantly correlated with lipid parameters (TC, TG, LDL-C, HDL-C) were selected from genome-wide association studies (GWAS) as instrumental variables (IV) (P < 5.0 × 10-8). Summary data for ED was gathered from a GWAS with a sample size of (n = 17,353 cases/28,210 controls). The inverse variance weighted (IVW) method was employed as the primary mendelian randomization (MR) analysis method to assess causal effects. Causal estimates were represented as odds ratios (OR) with 95% confidence intervals (CI). RESULTS: Results from the case-control study revealed that, when compared with the control group, levels of LDL-C, TG, UA, LDL-C/HDL-C, TG/HDL-C, and TC/HDL-C in the ED group were significantly elevated (P < 0.01), while HDL-C was significantly decreased (P < 0.01) in the ED group. Multivariate logistic regression analysis indicated LDL-C/HDL-C as a risk factor for both the incidence and severity of ED (P < 0.001). Two-sample MR analysis demonstrated no significant causal correlation between lipid parameters-LDL-C (OR, 0.98, 95% CI, 0.88-1.08, P = 0.616), HDL-C (OR, 1.07, 95% CI: 0.96-1.19, P = 0.249), TC (OR, 1.07, 95% CI, 0.96-1.18, P = 0.208), TG (OR, 0.98, 95% CI, 0.80-1.13, P = 0.579) -and an increased risk of ED (all P > 0.05). CONCLUSIONS: The case-control analysis ascertained a significant association between LDL-C, HDL-C, LDL-C/HDL-C, and ED and its severity. However, results from the MR study do not support a causal role of lipid parameters in ED.

The six-degrees-of-freedom attitude measurement instrument for the large aperture mirror using the prepressing sensors and flexible supporting.

To achieve precise measurement of a large aperture mirror, a six-degrees-of-freedom (6-DOF) measurement instrument is designed to monitor and calculate the real-time attitude of the mirror. Magnetoelectric displacement sensors are prepressed, and a flexible sensor supporting is designed to achieve high-accuracy measurement. The relationship between 6-DOF displacements of the mirror and the six sensor values can be obtained using the coordinate system transformation and Jacobian matrix. The Newton's iteration method is used to decouple the strong coupling measurement system, and 6-DOF displacements are obtained. The displacements directly measured by using laser sensors are compared with the calculated values in the experiments, the minimum average error of the measured displacement is 1.87%, and the mean difference of the displacement is 0.43 µm.

Highly Selective and Rapid "Turn-On" Fluorogenic Chemosensor for Detection of Salicylic Acid in Plants and Food Samples.

Salicylic acid (SA) is one of the chemical molecules, involved in plant growth and immunity, thereby contributing to the control of pests and pathogens, and even applied in fruit and vegetable preservation. However, only a few tools have ever been designed or executed to understand the physiological processes induced by SA or its function in plant immunity and residue detection in food. Hence, three Rh6G-based fluorogenic chemosensors were synthesized to detect phytohormone SA based on the "OFF-ON" mechanism. The probes showed high selectivity, ultrafast response time (<60 s), and nanomolar detection limit for SA. Moreover, the probe possessed outstanding profiling that can be successfully used for SA imaging of callus and plants. Furthermore, the fluorescence pattern indicated that SA could occur in the distal transport in plants. These remarkable results contribute to improving our understanding of the multiple physiological and pathological processes involved in SA for plant disease diagnosis and for the development of immune activators. In addition, SA detection in some agricultural products used probes to extend the practical application because its use is prohibited in some countries and is harmful to SA-sensitized persons. Interestingly, the as-obtained test paper displayed that SA could be imaged by ultraviolet (UV) and was directly visible to the naked eye. Given the above outcomes, these probes could be used to monitor SA in vitro and in vivo, including, but not limited to, plant biology, food residue detection, and sewage detection.

Low-dose atorvastatin protects skeletal muscle mitochondria in high-fat diet-fed mice with mitochondrial autophagy inhibition and fusion enhancement.

Despite the great clinical benefits of statins in cardiovascular diseases, their widespread use may lead to adverse muscle reactions associated with mitochondrial dysfunction. Some studies have demonstrated that statins provide substantial improvement to skeletal muscle health in mice. Our previous study found that oral treatment with atorvastatin (Ator, 3 mg/kg) protected myocardial mitochondria in high-fat diet (HFD)-fed mice. Therefore, this study aimed to explore the influence of low-dose Ator (3 mg/kg) on mitochondria in skeletal muscle under cholesterol overload. Male C57BL/6J mice were fed a HFD for 18 weeks and orally administered Ator (3 mg/kg) during the last 12 weeks. Ator treatment had no effects on elevated serum cholesterol and glucose levels in HFD-fed mice. Serum creatine kinase levels and the cross-sectional area of muscle cells were not affected by HFD feeding or Ator treatment. Increased expression of PINK1-LC3 II (activated mitophagy), MFN2 (fusion), and PGC-1α (biogenesis) proteins was induced in the skeletal muscles of HFD-fed mice. Treatment with Ator inhibited PINK1 and LC3 II protein expression, but further promoted MFN1, MFN2, and OPA1 expression. The impairments in mitochondrial quality and morphology in HFD-fed mice were attenuated by treatment with Ator. Furthermore, Ator treatment enhanced glucose oxidation capacity and restored ATP production in the skeletal muscles of HFD-fed mice. The study reveals that low-dose Ator has a protective effect on muscle mitochondria in mice, likely through inhibiting mitophagy and enhancing mitochondrial fusion. This suggests that skeletal muscle mitochondria may be one of low-dose Ator-mediated protective targets.

Characterization, in vitro digestibility, antioxidant activity and intestinal peristalsis in zebrafish of Dioscorea opposita polysaccharides.

The soluble crude polysaccharides from Dioscorea opposita (DOP1 and DOP2) were prepared and characterized. DOP1 and DOP2 obtained carbohydrate (65.71% and 70.18%, respectively), uronic acid (63.71% and 24.84%, respectively) and protein (8.09% and 9.51%, respectively) with molecular weight of 49.24 kDa and 21.62 kDa, respectively. DOP samples were mainly composed of mannose, glucose, galacturonic acid, galactose, and glucuronic acid. The digestibility in vitro, antioxidant activity and intestinal peristalsis effect were then investigated. DOP1 and DOP2 were degraded with decreased molecular weights (39.58 kDa and 18.56 kDa respectively), increased reducing sugar contents (from 16.95% to 19.27%; 12.45% to 15.50% respectively) and free monosaccharides (from 0.89% to 1.42%; 0.90% to 1.14% respectively) after gastric digestion. Both DOP1 and DOP2 were resistant to intestinal digestion, suggesting that DOP samples can be considered as a dietary fiber. Additionally, DOP1 and DOP2 exhibited antioxidant activities positively correlated with the concentration and remained the activities after gastrointestinal digestion in vitro. Furthermore, DOP reduced the fluorescence intensity significantly, indicating DOP can promote the intestinal peristalsis of zebrafish larvae (5 pdf) at 500 µg/mL. Therefore, DOP1 and DOP2 have a better functionality as dietary fibers, including antioxidant activity and intestinal peristalsis promotion, which can be developed as functional foods.

Divergent Enzymatic Assembly of a Comprehensive 64-Membered IgG N-Glycan Library for Functional Glycomics.

N-Glycosylation, a main post-translational modification of Immunoglobulin G (IgG), plays a significant role in modulating the immune functions of IgG. However, the precise function elucidation of IgG N-glycosylation remains impeded due to the obstacles in obtaining comprehensive and well-defined N-glycans. Here, an easy-to-implement divergent approach is described to synthesize a 64-membered IgG N-glycan library covering all possible biantennary and bisected N-glycans by reprogramming biosynthetic assembly lines based on the inherent branch selectivity and substrate specificity of enzymes. The unique binding specificities of 64 N-glycans with different proteins are deciphered by glycan microarray technology. This unprecedented collection of synthetic IgG N-glycans can serve as standards for N-glycan structure identification in complex biological samples and the microarray data enrich N-glycan glycomics to facilitate biomedical applications.

Nanoparticles carrying paclitaxel and anti-miR-221 for breast cancer therapy triggered by ultrasound.

Nanomaterials have been well demonstrated to have the potential to be used for tumor cell-targeted drug delivery. Targeted inhibition of miR-221 was proved to promote the sensitivity of triple genitive breast cancer (TNBC) cells to chemo-drugs. In order to improve the chemotherapeutic effect in TNBC, herein, we developed a novel kind of nanoparticles shelled with PLGA and loaded with perfluoropentane (PFP), paclitaxel (PTX), and anti-miR-221 inhibitor, which was named PANP. Ultrasound-triggered vaporization of PFP in PANPs was utilized for real-time imaging track of the nanoparticles in vivo. In addition, macrophages were applied for the internalization of PANPs to form RAW-PANP with strong chemotaxis to accumulate around cancer cells. Nanoparticles with different contents did not cause M2 polarization compared with the control group but caused polarization toward M1. We compared the inherent tumor-homing behavior of macrophages containing different contents with that of normal macrophages and no significant abnormalities were observed. After injection into the tumor-burden mice, RAW-PANPs showed enrichment within tumor tissues. Upon the ultrasound cavitation-triggered burst, PTX was released in the tumor. Meanwhile, the release of anti-miR-221 improved the sensitivity of tumor cells to PTX. As a result, RAW-PANPs showed high efficiency in suppressing TNBC cell proliferation in vitro and inhibiting tumor growth and progression in vivo. The treatments did not induce liver, heart, or kidney injury. In conclusion, the current study not only developed a macrophage-carried, ultrasound-triggered, cancer cell-targeted chemotherapeutic system, but also demonstrated a miRNA-based technique to promote drug sensitivity of cancer cells, which holds strong potential to treat patients with TNBC, especially for those suffering drug-resistance. The innovation of this study is to use macrophages to deliver nanoparticles to the tumors and then use ultrasound locally to burst the nanoparticles to release the miRNA and PTX.

High-fat diet causes mitochondrial damage and downregulation of mitofusin-2 and optic atrophy-1 in multiple organs.

High-fat consumption promotes the development of obesity, which is associated with various chronic illnesses. Mitochondria are the energy factories of eukaryotic cells, maintaining self-stability through a fine-tuned quality-control network. In the present study, we evaluated high-fat diet (HFD)-induced changes in mitochondrial ultrastructure and dynamics protein expression in multiple organs. C57BL/6J male mice were fed HFD or normal diet (ND) for 24 weeks. Compared with ND-fed mice, HFD-fed mice exhibited increased body weight, cardiomyocyte enlargement, pulmonary fibrosis, hepatic steatosis, renal and splenic structural abnormalities. The cellular apoptosis of the heart, liver, and kidney increased. Cellular lipid droplet deposition and mitochondrial deformations were observed. The proteins related to mitochondrial biogenesis (TFAM), fission (DRP1), autophagy (LC3 and LC3-II: LC3-I ratio), and mitophagy (PINK1) presented different changes in different organs. The mitochondrial fusion regulators mitofusin-2 (MFN2) and optic atrophy-1 (OPA1) were consistently downregulated in multiple organs, even the spleen. TOMM20 and ATP5A protein were enhanced in the heart, skeletal muscle, and spleen, and attenuated in the kidney. These results indicated that high-fat feeding caused pathological changes in multiple organs, accompanied by mitochondrial ultrastructural damage, and MFN2 and OPA1 downregulation. The mitochondrial fusion proteins may become promising targets and/or markers for treating metabolic disease.

Rhodamine-based fluorescent sensors for the rapid and selective off-on detection of salicylic acid and their use in plant cell imaging.

Salicylic acid (SA) is a key hormone that regulates plant growth and immunity, and understanding the physiologic processes induced by SA enables the development of highly pathogen-resistant crops. Here, we report the synthesis of three new SA-sensors (R1-R3) from hydroxyphenol derivatives of a rhodamine-acylhydrazone scaffold and their characterization by NMR and HRMS. Spectroscopic analyses revealed that structural variations in R1-R3 resulted in sensors with different sensitivities for SA. Sensor R2 (with the 3-hydroxyphenyl modification) outperformed R1 (2-hydroxyphenyl) and R3 (4-hydroxyphenyl). The SA-detection limit of R2 is 0.9 µM with an ultra-fast response time (<60 s). In addition, their plant imaging indicated that designed sensor R2 is useful for the further study of SA biology and the discovery and development of new inducers of plant immunity.

FoxO and rotund form a binding complex governing wing polyphenism in planthoppers.

Wing polyphenism is found in a variety of insects and offers an attractive model system for studying the evolutionary significance of dispersal. The Forkhead box O (FoxO) transcription factor (TF) acts as a wing-morph switch that directs wing buds developing into long-winged (LW) or short-winged morphs in wing-dimorphic planthoppers, yet the regulatory mechanism of the FoxO module remains elusive. Here, we identified the zinc finger TF rotund as a potential wing-morph regulator via transcriptomic analysis and phenotypic screening in the brown plathopper, Nilaparvata lugens. RNA interference-mediated knockdown of rotund antagonized the LW development derived from in the context of FoxO depletion or the activation of the insulin/insulin-like growth factor signaling cascade, reversing long wings into intermediate wings. In vitro binding assays indicated that rotund physically binds to FoxO to form the FoxO combinatorial code. These findings broaden our understanding of the complexity of transcriptional regulation governing wing polyphenism in insects.