Genetic dissection of intercellular interactions in vivo by membrane-permeable protein.

Unraveling cell-cell interaction is fundamental to understanding many biological processes. To date, genetic tools for labeling neighboring cells in mammals are not available. Here, we developed a labeling strategy based on the Cre-induced intercellular labeling protein (CILP). Cre-expressing donor cells release a lipid-soluble and membrane-permeable fluorescent protein that is then taken up by recipient cells, enabling fluorescent labeling of neighboring cells. Using CILP, we specifically labeled endothelial cells surrounding a special population of hepatocytes in adult mice and revealed their distinct gene signatures. Our results highlight the potential of CILP as a platform to reveal cell-cell interactions and communications in vivo.

Dynamics of Endothelial Cell Generation and Turnover in Arteries During Homeostasis and Diseases.

BACKGROUND: Endothelial cell (EC) generation and turnover by self-proliferation contributes to vascular repair and regeneration. The ability to accurately measure the dynamics of EC generation would advance our understanding of cellular mechanisms of vascular homeostasis and diseases. However, it is currently challenging to evaluate the dynamics of EC generation in large vessels such as arteries because of their infrequent proliferation. METHODS: By using dual recombination systems based on Cre-loxP and Dre-rox, we developed a genetic system for temporally seamless recording of EC proliferation in vivo. We combined genetic recording of EC proliferation with single-cell RNA sequencing and gene knockout to uncover cellular and molecular mechanisms underlying EC generation in arteries during homeostasis and disease. RESULTS: Genetic proliferation tracing reveals that ≈3% of aortic ECs undergo proliferation per month in adult mice during homeostasis. The orientation of aortic EC division is generally parallel to blood flow in the aorta, which is regulated by the mechanosensing protein Piezo1. Single-cell RNA sequencing analysis reveals 4 heterogeneous aortic EC subpopulations with distinct proliferative activity. EC cluster 1 exhibits transit-amplifying cell features with preferential proliferative capacity and enriched expression of stem cell markers such as Sca1 and Sox18. EC proliferation increases in hypertension but decreases in type 2 diabetes, coinciding with changes in the extent of EC cluster 1 proliferation. Combined gene knockout and proliferation tracing reveals that Hippo/vascular endothelial growth factor receptor 2 signaling pathways regulate EC proliferation in large vessels. CONCLUSIONS: Genetic proliferation tracing quantitatively delineates the dynamics of EC generation and turnover, as well as EC division orientation, in large vessels during homeostasis and disease. An EC subpopulation in the aorta exhibits more robust cell proliferation during homeostasis and type 2 diabetes, identifying it as a potential therapeutic target for vascular repair and regeneration.

3D Flower-like Nanospheres Constructed by Transition Metal Telluride Nanosheets as Sulfur Immobilizers for High-Performance Room-Temperature Na-S Batteries.

Room-temperature sodium-sulfur (RT Na-S) batteries hold immense promise as next-generation energy storage systems, owing to their exceptionally high theoretical capacity, abundant resources, eco-friendliness, and affordability. Nevertheless, their practical application is impeded by the shuttling effect of sodium polysulfides (NaPSs) and sluggish sulfur redox kinetics. In this study, an advanced strategy by designing 3D flower-like molybdenum telluride (MoTe2) as an efficient catalyst to promote sulfur redox for RT Na-S batteries is presented. The unique 3D flower-like MoTe2 effectively prevents NaPS shuttling and simultaneously offers abundant active catalytic sites facilitating polysulfide redox. Consequently, the obtained MoTe2/S cathode delivers an outstanding initial reversible capacity of 1015 mAh g-1 at 0.1 C, along with robust cycling stability of retaining 498 mAh g-1 at 1 C after 500 cycles. In addition, pouch cells are fabricated with the MoTe2 additive to deliver an ultrahigh initial discharge capacity of 890 mAh g-1 and remain stable over 40 cycles under practically necessary conditions, demonstrating the potential application in the commercialization of RT Na-S batteries.

Rational Design of Ion-Conductive Layer on Si Anode Enables Superior-Stable Lithium-Ion Batteries.

Silicon (Si) is considered a promising commercial material for the next-generation of high-energy density lithium-ion battery (LIB) due to its high theoretical capacity. However, the severe volume changes and the poor conductivity hinder the practical application of Si anode. Herein, a novel core-shell heterostructure, Si as the core and V3 O4 @C as the shell (Si@V3 O4 @C), is proposed by a facile solvothermal reaction. Theoretical simulations have shown that the in-situ-formed V3 O4 layer facilitates the rapid Li+ diffusion and lowers the energy barrier of Li transport from the carbon shell to the inner core. The 3D network structure constructed by amorphous carbon can effectively improve electronic conductivity and structural stability. Benefiting from the rationally designed structure, the optimized Si@V3 O4 @C electrode exhibits an excellent cycling stability of 1061.1 mAh g-1 at 0.5 A g-1 over 700 cycles (capacity retention of 70.0%) with an average Coulombic efficiency of 99.3%. In addition, the Si@V3 O4 @C||LiFePO4 full cell shows a superior capacity retention of 78.7% after 130 cycles at 0.5 C. This study opens a novel way for designing high-performance silicon anode for advanced LIBs.

Highly sensitive self-focused ultrasound transducer with a bionic back-reflector for multiscale-resolution photoacoustic microscopy.

In this study, we designed a self-focused ultrasonic transducer made of polyvinylidene fluoride (PVDF). This transducer involves a back-reflector, which is modeled after tapetum lucidum in the eyes of some nocturnal animals. The bionic structure reflects the ultrasound, which passes through the PVDF membrane, back to PVDF and provides a second chance for the PVDF to convert the ultrasound to electric signals. This design increases the amount of ultrasound absorbed by the PVDF, thereby improving the detection sensitivity. Both ultrasonic and photoacoustic (PA) experiments were conduct to characterize the performance of the transducer. The results show that the fabricated transducer has a center frequency of 13.07 MHz, and a bandwidth of 96% at -6 dB. With an acoustic numerical aperture (NA) of 0.64, the transducer provides a lateral resolution of 140µm. Importantly, the bionic design improves the detection sensitivity of the transducer about 30%. Finally, we apply the fabricated transducer to optical-resolution (OR) and acoustic-resolution photoacoustic microscopy (AR-PAM) to achieve multiscale-resolution PA imaging. Imaging of the bamboo leaf and the leaf skeleton demonstrates that the proposed transducer can provide high spatial resolution, better imaging intensity and contrast. Therefore, the proposed transducer design will be useful to enhance the performance of multiscale-resolution PAM.

Multi-omics analysis reveals overactive inflammation and dysregulated metabolism in severe community-acquired pneumonia patients.

BACKGROUND: Severe community-acquired pneumonia (S-CAP) is a public health threat, making it essential to identify novel biomarkers and investigate the underlying mechanisms of disease severity. METHODS: Here, we profiled host responses to S-CAP through proteomics analysis of plasma samples from a cohort of S-CAP patients, non-severe (NS)-CAP patients, diseases controls (DCs), and healthy controls (HCs). Then, typical differentially expressed proteins were then validated by ELISA in an independent cohort. Metabolomics analysis was further performed on both the cohort 1 and cohort 2. Then, the proteomic and metabolomic signatures were compared between the adult and child cohorts to explore the characteristics of severe pneumonia patients. RESULTS: There were clear differences between CAP patients and controls, as well as substantial differences between the S-CAP and NS-CAP. Pathway analysis of changes revealed excessive inflammation, suppressed immunity, and lipid metabolic disorders in S-CAP cases. Interestingly, comparing these signatures between the adult and child cohorts confirmed that overactive inflammation and dysregulated lipid metabolism were common features of S-CAP patients, independent of age. The change proportion of glycerophospholipids, glycerolipids, and sphingolipids were obviously different in the adult and child S-CAP cases. CONCLUSION: The plasma multi-omics profiling revealed that excessive inflammation, suppressed humoral immunity, and disordered metabolism are involved in S-CAP pathogenesis.

MiR-150 levels are related to in-hospital mortality in non-HIV Pneumocystis pneumonia patients.

Pneumocystis pneumonia (PCP) is a common opportunistic infection that occurs in immunocompromised patients. Compared with HIV patients, PCP in non-HIV patients tends to follow up a more urgent course and poorer prognosis. Therefore, markers that could predict survival of PCP patients in non-HIV population are of great value. MiRNA-150 has been widely studied in many diseases since it has been identified as a vital regulator of immune cell differentiation and activation. We thus conduct this study aiming to evaluate the prognostic value of miR-150 level in non-HIV PCP. First, the expression levels of miR-150 were compared between PCP patients and healthy volunteers. The miR-150 levels in immune cells were also detected in PCP mouse models. Then the prognostic value of miR-150 was further assessed in another PCP population (n = 72). The expression levels of miR-150 were measured by reverse transcription real-time PCR (RT-PCR) technique. Our data demonstrated significantly decreased miR-150 expression levels in PCP patients and mouse models compared to controls. The miR-150 levels also decreased in various immune cells of PCP mouse models. With a cut-off value of 3.48, the area under the curve, sensitivity, specificity of miR-150 to predicate PCP mortality were 0.845, 68.2% and 96.0%, respectively. In conclusion, miR-150 expression value might serve as a potential biomarker to identify PCP patients at high risk of death.

Pneumocystis pneumonia (PCP) remains a fatal risk for immunosuppressed patients. MiR-150 takes part in immune regulation, and thus is involved in infection control. Our study indicated that the miR-150 expression may act as a potential biomarker for predicting mortality of PCP patients.

Changing eating to manage weight or shape: A cross-sectional and prospective study of the prevalence and correlates in a large Canadian adolescent cohort.

OBJECTIVE: The present study examined reports of changing eating to manage weight/shape over one year among adolescents. It also tested how changing eating for weight/shape was associated with physical activity (resistance training, moderate-to-vigorous physical activity; MVPA) and mental health (depressive symptoms, flourishing), and whether weight perceptions moderated these associations. METHODS: Participants were Canadian adolescents (N = 20,614, Mage ± SD = 14.4 ± 1.3, 52.9% girls) who completed self-report surveys in the 2020-2021 and 2021-2022 waves of the COMPASS study. Separate multilevel models were tested for each outcome. RESULTS: Approximately 30% of adolescents reported changing their eating to manage weight/shape at least once a week. More days of changing eating were associated with significantly higher depressive symptoms and lower flourishing cross-sectionally (b = 0.51, b = -0.27) and over time (b = 0.35, -0.20); the flourishing association over time was weaker for adolescents who perceived themselves as overweight relative to about right. More days of changing eating were also associated with more MVPA and resistance training cross-sectionally (b = 2.81, b = 0.19) and over time (b = 1.28, b = 10). The relationship between changing eating and MVPA over time was stronger for adolescents who perceived themselves as overweight relative to about right; whereas the cross-sectional relationship between changing eating and resistance training was weaker. CONCLUSIONS: Reports of changing eating to manage weight/shape were associated with divergent health outcomes; research into how and to what extreme adolescents are changing eating to manage weight/shape, and identity factors that may contribute to these differences, is warranted.

Fe(II)-Targeted PET/19F MRI Dual-Modal Molecular Imaging Probe for Early Evaluation of Anticancer Drug-Induced Acute Kidney Injury.

Ferroptosis, an iron-dependent regulated cell death, has been emerging as an early mechanism in anticancer drug-induced acute kidney injury (AKI) that may benefit therapeutic intervention. However, the lack of molecular imaging methods for in vivo detection of ferroptosis restricts the early diagnosis of anticancer drug-induced AKI. Herein, we developed a PET/19F MRI dual-modal imaging probe for the monitoring of ferroptosis in AKI by chemically conjugating the Fe(II)-sensitive artemisinin (Art) motif and macrocyclic ligand 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) to the CF3-modified polyhedral oligomeric silsesquioxane (POSS) clusters, denoted as the PAD probe. The PAD probe could be converted into PA*D in the presence of Fe(II) ions and subsequently be intercepted by biological macromolecules nearby, thereby enhancing the retention effect in ferroptotic cells and tissues. After labeling with 68Ga isotopes, the 68Ga-labeled PAD probe in cisplatin (CDDP)-induced AKI mice displayed a significantly higher renal uptake level than that in normal mice. Moreover, the PAD probe with a precise chemical structure, relatively high 19F content, and single 19F resonance frequency allowed for interference-free and high-performance19F MRI that could detect the onset of CDDP-induced AKI at least 24 h earlier than the typical clinical/preclinical assays. Our study provides a robust dual-modal molecular imaging tool for the early diagnosis and mechanistic investigation of various ferroptosis-related diseases.

Nitroaromatic Compounds from Secondary Nitrate Formation and Biomass Burning Are Major Proinflammatory Components in Organic Aerosols in Guangzhou: A Bioassay Combining High-Resolution Mass Spectrometry Analysis.

The limited characterization and detection capacity of unknown compounds hinder our understanding of the molecular composition of toxic compounds in PM2.5. The present study applied Fourier transform ion cyclotron resonance mass spectrometry coupled with negative and positive electrospray ionization sources (ESI-/ESI+ FT-ICR-MS) to probe the molecular characteristics and dynamic formation processes of the effective proinflammatory components in organic aerosols (OAs) of PM2.5 in Guangzhou for one year. We detected abundant proinflammatory molecules in OAs, mainly classified as CHON compounds (compounds composed of C, H, O, and N atoms) in elemental and nitroaromatic compounds (NACs) in structures. From the perspective of the formation process, we discovered that these proinflammatory molecules, especially toxic NACs, were largely driven by secondary nitrate formation and biomass burning (in emission source), as well as SO2 (in atmospheric evolution). In addition, our results indicated that the secondary processes had replaced the primary emission as the main contributing source of the toxic proinflammatory compounds in OAs. This study highlights the importance of community measures to control the production of nitroaromatic compounds derived from secondary nitrate formation and biomass burning in urban areas.

PASylation improves pharmacokinetic of liposomes and attenuates anti-PEG IgM production: An alternative to PEGylation.

PASylation, which was recently reported as the conjugation of pharmacologically active compounds with polypeptide sequences mainly made of proline, alanine and serine, has been proposed as an alternative to PEGylation. In this study, we designed PAS-modified liposomes (PASylated liposomes) and studied the effect of the incorporation of PAS-lipid on the stability and pharmacokinetic properties of liposomes, and compared them both in vitro and in vivo to PEGylated liposomes. Results showed that PASylated liposomes modified with single-chained PAS-lipid C16-(PA3)7 (SC-PAS-Lip) showed comparable storage and serum stability to PEGylated liposomes (PEG-Lip), and a significantly decreased macrophage uptake compared with unmodified liposomes. SC-PAS-Lip displayed long circulating pharmacokinetic profile which was not impacted by the repeated administration of liposomes, and they were less likely to induce the production of anti-PEG IgM compared with PEGylated liposomes, presenting PASylation as an alternative liposome modification strategy to PEGylation.

Construction and evaluation of an antioxidant synergistic system containing vitamin C and vitamin E.

AIMS: The aim of this study is to develop a liposome that could exert unparalleled antioxidant effects. In the present study, a vitamin C (VC)/vitamin E (VE)-co-loaded multivesicular liposome (VCVE-MVL) was constructed. METHODS: Vitamins were encapsulated in soybean phosphatidylcholine (SPC) and cholesterol (CHO) by multi-emulsification method. The concentration of VC was determined by Fast Blue method. The concentration of VE was determined by high performance liquid chromatography (HPLC). Vitamin antioxidant capacity in vitro and in vivo was determined using ß-carotene bleaching. RESULTS: VCVE-MVL with particle diameter of 848.55 ± 0.29 nm and SPAN of 0.16 ± 0.11 were obtained. The encapsulation efficiency of VC reached 48.51% (w/w)±0.15. Compared with VC/VE solution, VCVE-MVL had a higher permeation efficiency. In addition, the in vitro and ex-vivo antioxidant tests verified the adequate antioxidant activity of VCVE-MVL. CONCLUSIONS: In conclusion, the antioxidant synergistic system we constructed and demonstrated its potential applications in the cosmetics industry.

Liraglutide inhibits AngII-induced cardiac fibroblast proliferation and ECM deposition through regulating miR-21/PTEN/PI3K pathway.

BACKGROUND: Cardiac fibrosis characterized with the aberrant proliferation of cardiac fibroblasts and extracellular matrix (ECM) deposition is a major pathophysiological feature of atrial fibrillation (AF). Liraglutide has exerted an alleviative role in various cardiovascular diseases, and can also regulate the level of microRNAs (miRNAs). It has been reported that miR-21 modulated cardiac fibrosis in AF. However, the regulative effect of liraglutide on atrial fibrosis via miR-21 and the underlying mechanism are still unclear. METHODS: The atrial fibroblasts were isolated from the heart of C57BL/6 mice, and treated with Angiotensin II (AngII) and liraglutide. The proliferation, migration, and ECM deposition were determined by cell counting Kit-8 (CCK-8), Brdu, transwell assay, cell scratch, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blot and immunofluorescence. The underlying mechanism was explored after transfection of miR-21 mimics into cells. RESULTS: Liraglutide inhibited proliferation, migration, invasion of fibroblast cell and ECM deposition in AngII-stimulated cardiac fibroblasts. Additionally, liraglutide decreased the AngII-induced increase in the expression level of miR-21, but enhanced the expression of phosphatase and tensin homolog (PTEN), a target of miR-21, thereby suppressing the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway. Rescue assay confirmed that overexpression of miR-21 counteracted the ameliorative effect of liraglutide on the proliferation, migration, invasion and ECM deposition in fibroblasts stimulated by AngII. CONCLUSIONS: Liraglutide dampened AngII-induced proliferation and migration, and ECM deposition of cardiac fibroblast via modulating miR-21/PTEN/PI3K pathway.

Mitigating Electron Leakage of Solid Electrolyte Interface for Stable Sodium-Ion Batteries.

The interfacial stability is highly responsible for the longevity and safety of sodium ion batteries (SIBs). However, the continuous solid-electrolyte interphase(SEI) growth would deteriorate its stability. Essentially, the SEI growth is associated with the electron leakage behavior, yet few efforts have tried to suppress the SEI growth, from the perspective of mitigating electron leakage. Herein, we built two kinds of SEI layers with distinct growth behaviors, via the additive strategy. The SEI physicochemical features (morphology and componential information) and SEI electronic properties (LUMO level, band gap, electron work function) were investigated elaborately. Experimental and calculational analyses showed that, the SEI layer with suppressed growth delivers both the low electron driving force and the high electron insulation ability. Thus, the electron leakage is mitigated, which restrains the continuous SEI growth, and favors the interface stability with enhanced electrochemical performance.

Nifuroxazide ameliorates pulmonary fibrosis by blocking myofibroblast genesis: a drug repurposing study.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a serious interstitial lung disease with a complex pathogenesis and high mortality. The development of new drugs is time-consuming and laborious; therefore, research on the new use of old drugs can save time and clinical costs and even avoid serious side effects. Nifuroxazide (NIF) was originally used to treat diarrhoea, but more recently, it has been found to have additional pharmacological effects, such as anti-tumour effects and inhibition of inflammatory diseases related to diabetic nephropathy. However, there are no reports regarding its role in pulmonary fibrosis. METHODS: The therapeutic effect of NIF on pulmonary fibrosis in vivo was measured by ELISA, hydroxyproline content, H&E and Masson staining, immunohistochemistry (IHC) and western blot. Immune cell content in lung tissue was also analysed by flow cytometry. NIF cytotoxicity was evaluated in NIH/3T3 cells, human pulmonary fibroblasts (HPFs), A549 cells and rat primary lung fibroblasts (RPLFs) using the MTT assay. Finally, an in vitro cell model created by transforming growth factor-ß1 (TGF-ß1) stimulation was assessed using different experiments (immunofluorescence, western blot and wound migration assay) to evaluate the effects of NIF on the activation of NIH/3T3 and HPF cells and the epithelial-mesenchymal transition (EMT) and migration of A549 cells. RESULTS: In vivo, intraperitoneal injection of NIF relieved and reversed pulmonary fibrosis caused by bleomycin (BLM) bronchial instillation. In addition, NIF inhibited the expression of a variety of cellular inflammatory factors and immune cells. Furthermore, NIF suppressed the activation of fibroblasts and EMT of epithelial cells induced by TGF-ß1. Most importantly, we used an analytical docking experiment and thermal shift assay to further verify that NIF functions in conjunction with signal transducer and activator of transcription 3 (Stat3). Moreover, NIF inhibited the TGF-ß/Smad pathway in vitro and decreased the expression of phosphorylated Stat3 in vitro and in vivo. CONCLUSION: Taken together, we conclude that NIF inhibits and reverses pulmonary fibrosis, and these results support NIF as a viable therapeutic option for IPF treatment.

New biopsy after antibiotic treatment: effect on outcomes of assisted reproduction in patients with infertility and chronic endometritis.

RESEARCH QUESTION: What is the effect of chronic endometritis on patients with infertility, the necessity of endometrial re-examination and the effect of improving chronic endometritis after one cycle of antibiotic treatment on pregnancy outcomes? DESIGN: Infertile patients (n = 4003) who underwent IVF and intracytoplasmic sperm injection treatment were included. Pregnancy outcomes of groups positive for chronic endometritis were compared with groups that were negative (group 1). Patients that were positive were divided into the chronic endometritis new biopsy group (group 2) and chronic endometritis non-re-examination group (group 3). After doxycycline treatment and re-examination, the chronic endometritis new biopsy group was divided into improved chronic endometritis group (ICE) and not-improved chronic endometritis group (NICE), and their general indicators and reproductive outcomes were compared. RESULTS: No significant difference was observed in embryo implantation, early or late pregnancy loss, ectopic pregnancy, clinical pregnancy and live birth rates between groups 2 and 3. The clinical pregnancy and live birth rates in the NICE group were significantly lower than those in the ICE group (P = 0.008 and P = 0.001, respectively). After controlling for potential confounding factors, age, average number of high-quality embryos, endometrial thickness on the day of embryo transfer and number and type of embryo transfer were factors associated with live birth rates. CONCLUSIONS: Endometrial re-examination of women with chronic endometritis treated with doxycycline had no effect on pregnancy outcomes. The first cycle of doxycycline treatment could effectively improve reproductive outcomes of women with five or more CD138+ cells/high-power field.

Design, synthesis and biological evaluation of a series of novel pyrrolo[2,3-d]pyrimidin/pyrazolo[3,4-d]pyrimidin-4-amine derivatives as FGFRs-dominant multi-target receptor tyrosine kinase inhibitors for the treatment of gastric cancer.

Gastric cancer is the second most lethal cancer across the world. With the progress in therapeutic approaches, the 5-year survival rate of early gastric cancer can reach > 95%. However, the prognosis and survival time of advanced gastric cancer is still somber. Therefore, more effective targeted therapies for gastric cancer treatment are urgently needed. FGFR, VEGFR and other receptor tyrosine kinases have recently been suggested as potential targets for gastric cancer treatment. We herein report the discovery of pyrrolo[2,3-d]pyrimidin/pyrazolo[3,4-d]pyrimidin-4-amine derivatives as a new class of FGFRs-dominant multi-target receptor tyrosine kinase inhibitors. SAR assessment identified the most active compounds 8f and 8k, which showed excellent inhibitory activity against a variety of receptor tyrosine kinases. Moreover, 8f and 8k displayed excellent potency in the SNU-16 gastric cancer cell line. Furthermore, 8f and 8k could inhibit FGFR1 phosphorylation and downstream signaling pathways as well as induce cell apoptosis. In vivo, 8f and 8k suppress tumor growth in the SNU-16 xenograft model without inducing obvious toxicity. These findings raise the possibility that compounds 8f and 8k might serve as potential agents for the treatment of gastric cancer.

Efficiency Assessment of Bacterial Cellulose on Lowering Lipid Levels In Vitro and Improving Lipid Metabolism In Vivo.

Bacterial cellulose (BC) is well known as a high-performance dietary fiber. This study investigates the adsorption capacity of BC for cholesterol, sodium cholate, unsaturated oil, and heavy metal ions in vitro. Further, a hyperlipidemia mouse model was constructed to investigate the effects of BC on lipid metabolism, antioxidant levels, and intestinal microflora. The results showed that the maximum adsorption capacities of BC for cholesterol, sodium cholate, Pb2+ and Cr6+ were 11.910, 16.149, 238.337, 1.525 and 1.809 mg/g, respectively. Additionally, BC reduced the blood lipid levels, regulated the peroxide levels, and ameliorated the liver injury in hyperlipidemia mice. Analysis of the intestinal flora revealed that BC improved the bacterial community of intestinal microflora in hyperlipidemia mice. It was found that the abundance of Bacteroidetes was increased, while the abundance of Firmicutes and Proteobacteria was decreased at the phylum level. In addition, increased abundance of Lactobacillus and decreased abundance of Lachnospiraceae and Prevotellaceae were obtained at the genus level. These changes were supposed to be beneficial to the activities of intestinal microflora. To conclude, the findings prove the role of BC in improving lipid metabolism in hyperlipidemia mice and provide a theoretical basis for the utilization of BC in functional food.

Coordinating the Mechanisms of Action of Ferroptosis and the Photothermal Effect for Cancer Theranostics.

Combination therapy based on different mechanisms of cell death has shown promise in tumor therapy. However, when different modalities are integrated, the maximum synergy of the therapeutic effects is often lacking in the design. Herein, we report a cancer theranostic nanomedicine formula developed by considering the mechanisms of action of ferroptosis and the photothermal effect in combination therapy. The croconaine molecule was encapsulated as both a photothermal converter and an iron-chelating agent with BSA, thus leading to biocompatible and stable Cro-Fe@BSA nanoparticles (NPs). The Cro-Fe@BSA NPs in the tumor milieu showed an activated photothermal effect leading to enhanced radical formation owing to the temperature-dependent Fenton reaction kinetics, while radical formation during ferroptosis in turn prevented the heat-induced formation of heat shock proteins and thus the self-protection mechanism of cancer cells in response to heat. The activatable photoacoustic and magnetic resonance imaging performance of the Cro-Fe@BSA NPs also enabled safe and reliable cancer theranostics.

Aquaporin 3 promotes human extravillous trophoblast migration and invasion.

PROBLEM: Does aquaporin 3 (AQP3) affect the migration and invasion of human extravillous trophoblast (HTR8/Svneo) cells? METHOD OF STUDY: A lentivirus infection system was used to construct stable cell lines with either AQP3 knockdown or overexpression. RT-PCR and western blotting were used to verify the efficiencies of AQP3 knockdown or overexpression in HTR8/Svneo cells at mRNA and protein levels, respectively. Cell Counting Kit-8 and flow cytometry assays were used to detect the influence of AQP3 knockdown or overexpression on proliferation and apoptosis of HTR8/Svneo cells. In addition, wound healing and Transwell invasion assays were used to detect the effects of AQP3 knockdown or overexpression on migration and invasion capabilities of HTR8/Svneo cells. An Agilent gene chip was used to screen for significant differentially expressed genes after AQP3 knockdown. Finally, mechanisms by which AQP3 influences the migration and invasion of HTR8/Svneo cells were explored using bioinformatic analysis. RESULTS: Compared with controls, migration and invasion capabilities of HTR8/Svneo cells were significantly reduced after AQP3 knockdown, and significantly increased after AQP3 overexpression. Subsequent bioinformatic analysis of gene chip expression profiles indicated downregulation of genes related to adhesion such as PDGF-B, as well as signaling pathways (such as PIK3/AKT, NF-κB, and TNF) after AQP3 knockdown. CONCLUSIONS: AQP3 could significantly promote migration and invasion capabilities of human extravillous trophoblasts, it may mediate embryo invasion and adhesion to endometrium by regulating PDGF-B, PIK3/AKT signaling pathways, although this requires further verification.