Ultra-High-Performance Liquid Chromatography-Electrospray Ionization-High-Resolution Mass Spectrometry for Distinguishing the Origin of Ellagic Acid Extracts: Pomegranate Peels or Gallnuts.

Ellagic acid, known for its various biological activities, is widely used. Ellagic acid from pomegranate peels is safe for consumption, while that from gallnuts is only suitable for external use. However, there is currently no effective method to confirm the source of ellagic acid. Therefore, this study establishes an analysis method using ultra-high-performance liquid chromatography-electrospray ionization-high-resolution mass spectrometry (UHPLC-ESI-HR-MS) to identify the components of crude ellagic acid extracts from pomegranate peels and gallnuts. The analysis revealed that there was a mix of components in the crude extracts, such as ellagic acid, palmitic acid, oleic acid, stearic acid, and 9(10)-EpODE. Furthermore, it could be observed that ellagic acid extracted from gallnuts contained toxic substances such as anacardic acid and ginkgolic acid (15:1). These components could be used to effectively distinguish the origin of ellagic acid from pomegranate peels or gallnuts. Additionally, a rapid quantitative analysis method using UHPLC-ESI-MS with multiple reaction monitoring (MRM) mode was developed for the quality control of ellagic acid products, by quantifying anacardic acid and ginkgolic acid (15:1). It was found that one of three ellagic acid health care products contained ginkgolic acid (C15:1) and anacardic acid at more than 1 ppm.

MOF-polymer composites with well-distributed gold nanoparticles for visual monitoring of homocysteine.

The distribution of gold nanoparticles (AuNPs) on the surface of a metal-organic framework (MOF) plays a crucial role in the catalytic performance of MOF-AuNP composites. This study describes how the physical adsorption (PH@AuNPs-on-U) and chemical modification of AuNPs on the surface of UiO-66-NH2 (U) affect the composites' catalytic efficiency. After 2-vinyl-4,4-dimethyl-2-oxazolin-5-one (VD) linked to poly(N-2-hydroxypropyl methacrylamide) (PH) with U (UVD-PH), UVD-PH@AuNPs composites were constructed with PH as the capping and reducing reagent. The composites exhibited higher peroxidase (POD)-like activity than PH@AuNPs-on-U for oxidising 3,3'5,5'-tetramethylbenzidine (TMB) with H2O2. The approach demonstrated that the proposed composite-based nanozymes could significantly enhance their catalytic activity and had a highly uniform distribution of PH@AuNPs on the surface of UVD. An assay with the nanozymes for visual detection of homocysteine (Hcy) was developed, displaying a good linear relationship (R2 = 0.998) ranging from 3.34 µM to 30.0 µM and a detection of limit of 0.3 µM. Additionally, the UVD-PH@AuNPs-TMB-H2O2 system successfully monitored serum Hcy after intraperitoneal injection in rats. This study paves a new way for developing MOF-AuNPs with highly uniform surface distribution of polymer@AuNPs to boost its catalytic activity and to detect drugs in real bio-samples.

Boosting the LAC-like activity of tetrapeptide capped copper nanoparticle-based nanozymes for colorimetric determination of adrenaline.

Enzymatic activity is important for a variety of technological applications, but the limited stability and complex structures of enzymes often limit their use. Therefore, designing powerful nanomaterial catalysts that are more stable and have higher catalytic activity than natural catalysts has been the pursuit of biotechnology. Here, inspired by electron transfer and the active site of laccase (LAC), four types of copper particles with LAC-like activity were synthesized using a simple hydrothermal method. Copper particles coated with the L-phenylalanine (F)-L-phenylalanine (F)-L-cysteine (C)-L-histidine (H) tetrapeptide exhibited higher LAC-like activity compared to those coated with a CH dipeptide, C, and H. This enhancement could be attributed to the higher structural homology and amino acid composition similarity with the natural LAC active center. The FFCH@CuNP nanozyme was employed for adrenaline detection, and it demonstrated outstanding activity, stability, and recyclability. Additionally, a method for the quantitative detection of adrenaline was established using a smartphone based on the FFCH@CuNP nanozymes. And the FFCH@CuNPs exhibited excellent sensitivity and specificity to adrenaline in a saliva-based test. Therefore, this work provides a reasonable pathway for the design of catalysts for future biotechnological and industrial applications.

Golgi-targeting viscosity probe for the diagnosis of Alzheimer's disease.

Early diagnosis and intervention of Alzheimer's disease (AD) are particularly important to delay the pathological progression. Although fluorescent probes have been widely employed for investigating and diagnosing AD, their biological applications are significantly restricted due to the low penetration ability of the blood-brain barrier (BBB) in vivo. In this study, we reported the first Golgi-targeted two-photon (TP) fluorescent probe, DCM-DH, for detecting viscosity in the Golgi apparatus. The probe was rationally designed to exhibit superior analytical performance including high sensitivity, specific Golgi-targeting, efficient BBB penetration ability, and deep tissue penetration (247 µm) in the brains of AD model mice. Using the probe, we demonstrated that the fluorescence intensity in the human liver cancer cell (HepG2 cells) was higher than that of human normal liver cell (LO2 cells), and the brain viscosity of AD model mice increased significantly. We anticipate that this competent tool could be easily extended to other AD biomarkers for fundamental research on this detrimental disease.

Enhancing the catalytic performance of MOF-polymer@AuNP-based nanozymes for colorimetric detection of serum L-cysteine.

The dispersion of gold nanoparticles (AuNPs) on a metal-organic framework (MOF) surface greatly affects the catalytic activity of the material. However, regulating the catalytic performance of AuNP-MOF composite-based nanozymes is a great challenge. Herein, poly(dimethylvinyloxazolinone) (PV) was chemically bonded on the surface of UiO-66-NH2 (U66), followed by modification of pepsin (Pep) on the PV chains. U66-PV-Pep@AuNP composite nanozymes were fabricated after the AuNPs formed in situ with Pep as the capping and reducing reagent. Compared to Pep@AuNPs that were physically adsorbed onto the surface of U66, the U66-PV-Pep@AuNP composites exhibited superior peroxidase (POD)-mimetic activity in the oxidation of 3,3'5,5'-tetramethylbenzidine (TMB) with H2O2. Considering the surface dispersion uniformity and local concentration of Pep@AuNPs on the surface of the U66-PV-Pep@AuNP composites, the principle for improving the catalytic performance of the proposed nanozymes was explored. Furthermore, it was observed that the introduction of L-cysteine (L-Cys) into the U66-PV-Pep@AuNP-TMB-H2O2 system significantly reduced its oxidation activity and faded the color, allowing the development of a highly selective and sensitive colorimetric method for L-Cys detection. The UV-vis absorption intensity of oxTMB showed a good linear relationship with the concentration of L-Cys in the range of 2.5-40.0 µM (R2 = 0.996), with a detection limit of 0.33 µM. The proposed protocol using U66-PV-Pep@AuNP nanozymes was applied to monitor rat serum L-Cys following intraperitoneal injection. This study paves the way for the design and construction of MOF-polymer@AuNP nanozymes for drug detection in real bio-samples.

Liposomes embedded with PEGylated iron oxide nanoparticles enable ferroptosis and combination therapy in cancer.

Ferroptosis, an iron-dependent regulated cell death process driven by excessive lipid peroxides, can enhance cancer vulnerability to chemotherapy, targeted therapy and immunotherapy. As an essential upstream process for ferroptosis activation, lipid peroxidation of biological membranes is expected to be primarily induced by intrabilayer reactive oxygen species (ROS), indicating a promising strategy to initiate peroxidation by improving the local content of diffusion-limited ROS in the lipid bilayer. Herein, liposomes embedded with PEG-coated 3 nm γ-Fe2O3 nanoparticles in the bilayer (abbreviated as Lp-IO) were constructed to promote the intrabilayer generation of hydroxyl radicals (•OH) from hydrogen peroxide (H2O2), and the integration of amphiphilic PEG moieties with liposomal bilayer improved lipid membrane permeability to H2O2 and •OH, resulting in efficient initiation of lipid peroxidation and thus ferroptosis in cancer cells. Additionally, Lp-IO enabled traceable magnetic resonance imaging and pH/ROS dual-responsive drug delivery. Synergistic antineoplastic effects of chemotherapy and ferroptosis, and alleviated chemotherapeutic toxicity, were achieved by delivering doxorubicin (capable of xCT and glutathione peroxidase inhibition) with Lp-IO. This work provides an efficient alternative for triggering therapeutic lipid peroxidation and a ferroptosis-activating drug delivery vehicle for combination cancer therapies.

Poly(N-2-hydroxypropylmethacrylamide)-capped gold nanoparticles as nanozymes with peroxidase-mimicking performance for the colorimetric monitoring of serum homocysteine.

Recently, nanozymes based on polymer-stabilized gold nanoparticles (AuNPs) have attracted more and more attention on account of their polymer-ligands' multiple functionalization sites. However, the contribution of polymer hydrogen bonding to the catalytic activity of AuNPs has received little attention. This study designed and fabricated poly(N-2-hydroxypropylmethacrylamide)-capped AuNPs (PHPAM@AuNPs) using a hydroxyl-rich polymer as the ligand. The PHPAM@AuNPs exhibited good peroxidase-mimicking activity capable of efficiently oxidizing 3,3'5,5'-tetramethylbenzidine (TMB) with H2O2. The effect of PHPAM hydrogen bonding on the catalytic activity of PHPAM@AuNPs was investigated. Under peroxidase-mimicking catalysis, homocysteine introduced a notable reduction in oxidation, allowing the creation of a colorimetric method for homocysteine detection with high selectivity and sensitivity. The ultraviolet-visible absorption intensity of oxidized TMB showed a strong linear relationship with homocysteine concentration in the range of 3.0-20.0 µM (R2 = 0.998), with a limit of detection of 0.4 µM. The proposed colorimetric protocol was used to monitor homocysteine in rat serum following intraperitoneal injection. This work provides a new way to refine AuNP-based nanozymes by relying on polymer-ligand hydrogen bonding. It has strong application potential in the analysis of endogenous molecules in real samples.

Abplatin(IV) inhibited tumor growth on a patient derived cancer model of hepatocellular carcinoma and its comparative multi-omics study with cisplatin.

BACKGROUND: Cisplatin, the alkylating agent of platinum(II) (Pt(II)), is the most common antitumor drug in clinic; however, it has many side effects, therefore it is higly desired to develop low toxicity platinum(IV) (Pt(IV)) drugs. Multi-omics analysis, as a powerful tool, has been frequently employed for the mechanism study of a certain therapy at the molecular level, which might be helpful for elucidating the mechanism of platinum drugs and facilitating their clinical application. METHODS: Strating form cisplatin, a hydrophobic Pt(IV) prodrug (CisPt(IV)) with two hydrophobic aliphatic chains was synthesized, and further encapsulated with a drug carrier, human serum albumin (HSA), to form nanoparticles, namely AbPlatin(IV). The anticancer effect of AbPlatin(IV) was investigated in vitro and in vivo. Moreover, transcriptomics, metabolomics and lipidomics were performed to explore the mechanism of AbPlatin(IV). RESULTS: Compared with cisplatin, Abplatin(IV) exhibited better tumor-targeting effect and greater tumor inhibition rate. Lipidomics study showed that Abplatin(IV) might induce the changes of BEL-7404 cell membrane, and cause the disorder of glycerophospholipids and sphingolipids. In addition, transcriptomics and metabolomics study showed that Abplatin(IV) significantly disturbed the purine metabolism pathway. CONCLUSIONS: This research highlighted the development of Abplatin(IV) and the use of multi-omics for the mechanism elucidation of prodrug, which is the key to the clinical translation of prodrug.

Temperature modulating the peroxidase-mimic activity of poly(N-isopropyl acrylamide) protected gold nanoparticles for colorimetric detection of glutathione.

More recently, loading polymer-ligand onto the surface of gold nanoparticles (AuNPs) as nanozymes has gained considerable attention. However, the efficient modulation of the nanozymes catalytic capability depending on external stimuli remains challenging. Herein, utilizing the thermo-responsive poly(N-isopropyl acrylamide) (PNIPAM) as a stabilizer and a reducing agent to make PNIPAM@AuNPs, we reported a straightforward and efficient protocol for modulating the peroxidase-mimic catalytic capability of PNIPAM@AuNPs in oxidation of 3,3',5,5'-tetramethyl benzidine (TMB)-H2O2 system by change of environmental temperature. More hydroxylradicals yielded and surface confinement effect induced by the coiled PNIPAM chains at high temperature could further significantly boost the nanozymes catalytic capability. In the presence of glutathione, the generation of oxidized TMB was inhibited and the absorption intensity of the reaction system decreased at 650 nm. The color-fadingproperty provided a highly selective assay for visualized and quantitative test of glutathione ranging 1.0 ～ 17.0 µM (R2 = 0.993), the limit of detection was 0.8 µM. Moreover, the proposed method exhibited a promising application in analysis of rat serum glutathione following an intravenous injection. The strategy supplies a facile guideline for preparation of stimuli-responsive polymer@AuNPs with improved peroxidase-mimic catalytic activity toward application in real living bio-systems.

Real-time analysis of metabolites in vivo by online extraction electrospray ionization mass spectrometry coupled to microdialysis.

In vivo and real-time analysis could reflect a more real biological state, which was of great significance to the study of complex life processes. In this work, we constructed an online extraction electrospray ionization (OE-ESI) ion source as the interface of microdialysis and mass spectrometry, which realized real-time analysis of metabolites in vivo without sample pretreatment process. The ion source was consisted of three coaxial capillaries, and the parameters of the ion source were optimized. The OE-ESI ion source could simultaneously extract, desalt and ionize the analyte, successfully perform MS analysis of analyte in high salt system, and overcome the ion suppression caused by salt ion. Compared with commercial ESI MS, the OE-ESI ion source had excellent salt tolerance and stability. MD-OE-ESI MS realized the real-time MS detection of metabolites in the living body, avoiding the complex desalting process. In the rat liver ischemia-reperfusion model, a total of 24 metabolites, including glucose, glutamate, glutamine, etc., were monitored in real time mode, and their concentrations had varying degrees of change during the experimental process compared with the control group. This platform, we believed, would be helpful for real-time monitoring of biological metabolites in vivo, and had great application prospects to study physiological processes.

A Novel Acyl-AcpM-Binding Protein Confers Intrinsic Sensitivity to Fatty Acid Synthase Type II Inhibitors in Mycobacterium smegmatis.

The fatty acid synthase type II (FAS-II) multienzyme system is the main target of drugs to inhibit mycolic acid synthesis in mycobacterium. Meromycolate extension acyl carrier protein (AcpM) serves as the carrier of fatty acyl chain shuttling among the individual FAS-II components during the progression of fatty acid elongation. In this paper, MSMEG_5634 in Mycobacterium smegmatis was determined to be a helix-grip structure protein with a deep hydrophobic pocket, preferring to form a complex with acyl-AcpM containing a fatty acyl chain at the C36-52 length, which is the medium product of FAS-II. MSMEG_5634 interacted with FAS-II components and presented relative accumulation at the cellular pole. By forming the MSMEG_5634/acyl-AcpM complex, which is free from FAS-II, MSMEG_5634 could transport acyl-AcpM away from FAS-II. Deletion of the MSMEG_5634 gene in M. smegmatis resulted in a mutant with decreased sensitivity to isoniazid and triclosan, two inhibitors of the FAS-II system. The isoniazid and triclosan sensitivity of this mutant could be restored by the ectopic expression of MSMEG_5634 or Rv0910, the MSMEG_5634 homologous protein in Mycobacterium tuberculosis H37Rv. These results suggest that MSMEG_5634 and its homologous proteins, forming a novel acyl-AcpM-binding protein family in mycobacterium, confer intrinsic sensitivity to FAS-II inhibitors.

Design and synthesis of a deep tissue penetrating near-infrared two-photon fluorescence probe for the specific detection of NQO1.

NAD(P)H:quinone oxidoreductase 1 (NQO1) is overexpressed in a broad range of human tumors but remains difficult to study. Herein, we report a novel two-photon fluorescent probe with NIR emission for NQO1 detection. The probe demonstrated superior analytical performance with a large Stokes shift and deep tissue penetration.

CYP311A1 in the anterior midgut is involved in lipid distribution and microvillus integrity in Drosophila melanogaster.

Lipids are either taken up from food sources or produced internally in specialized tissues such as the liver. Among others, both routes of lipid metabolism involve cytochrome P450 monooxygenases (CYPs). We sought to analyze the function of Cyp311a1 that has been shown to be expressed in the midgut of the fruit fly Drosophila melanogaster. Using a GFP-tagged version of CYP311A1 that is expressed under the control of its endogenous promoter, we show that Cyp311a1 localizes to the endoplasmic reticulum in epithelial cells of the anterior midgut. In larvae with reduced Cyp311a1 expression in the anterior midgut, compared to control larvae, the apical plasma membrane of the respective epithelial cells contains less and shorter microvilli. In addition, we observed reduction of neutral lipids in the fat body, the insect liver, and decreased phosphatidylethanolamine (PE) and triacylglycerols (TAG) amounts in the whole body of these larvae. Probably as a consequence, they cease to grow and eventually die. The microvillus defects in larvae with reduced Cyp311a1 expression are restored by supplying PE, a major phospholipid of plasma membranes, to the food. Moreover, the growth arrest phenotype of these larvae is partially rescued. Together, these results suggest that the anterior midgut is an import hub in lipid distribution and that the midgut-specific CYP311A1 contributes to this function by participating in shaping microvilli in a PE-dependent manner.

Polymer-capped gold nanoparticles as nanozymes with improved catalytic activity for the monitoring of serum ciprofloxacin.

More recently, gold nanoparticle (AuNP)-based nanozymes have become one of the burgeoning research hot topics. However, few studies have focused on these AuNP-nanozymes with polymers as ligands. A significant challenge is to reveal their catalytic mechanism and to improve their catalytic activity by changing the structures of the polymers. In this study, polyacrylamide (PAM) with different chain lengths was synthesized and used as the ligand to prepare PAM@AuNPs. The resultant nanozymes exhibited good peroxidase-like activity for catalyzing the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of hydrogen peroxide (H2O2). In particular, due to the electrostatic interaction between the negatively charged PAM@AuNPs and the positively charged drug, the addition of ciprofloxacin in the oxidation system induced the aggregation of PAM@AuNPs and produced more amount of reactive oxygen species, which greatly promoted the catalytic activity of PAM@AuNPs. Inspired by the attractive property, a highly selective and sensitive colorimetric assay for the monitoring of ciprofloxacin was created. A good linear relationship between the UV-Vis absorption intensity of PAM@AuNPs-TMB-H2O2 at 650 nm wavelength and the ciprofloxacin concentration was observed ranging from 1.0 µM to 12.0 µM (R2 = 0.998), providing the detection limit of 0.5 µM. The ciprofloxacin metabolism was further studied in rats. It reveals great potential of polymer protected AuNP-nanozymes in practical drug analysis.

Quantitative Lipidomics and Spatial MS-Imaging Uncovered Neurological and Systemic Lipid Metabolic Pathways Underlying Troglomorphic Adaptations in Cave-Dwelling Fish.

Sinocyclocheilus represents a rare, freshwater teleost genus endemic to China that comprises the river-dwelling surface fish and the cave-dwelling cavefish. Using a combinatorial approach of quantitative lipidomics and mass-spectrometry imaging (MSI), we demonstrated that neural compartmentalization of lipid distribution and lipid metabolism is associated with the evolution of troglomorphic traits in Sinocyclocheilus. Attenuated docosahexaenoic acid (DHA) biosynthesis via the Δ4 desaturase pathway led to reductions in DHA-phospholipids in cavefish cerebellum. Instead, cavefish accumulates arachidonic acid-phospholipids that may disfavor retinotectal arbor growth. Importantly, MSI of sulfatides coupled with immunostaining of myelin basic protein and transmission electron microscopy images of hindbrain axons revealed demyelination in cavefish raphe serotonergic neurons. Demyelination in cavefish parallels the loss of neuroplasticity governing social behavior such as aggressive dominance. Outside the brain, quantitative lipidomics and qRT-PCR revealed systemic reductions in membrane esterified DHAs in the liver, attributed to suppression of genes along the Sprecher pathway (elovl2, elovl5, and acox1). Development of fatty livers was observed in cavefish; likely mediated by an impeded mobilization of storage lipids, as evident in the diminished expressions of pnpla2, lipea, lipeb, dagla, and mgll; and suppressed ß-oxidation of fatty acyls via both mitochondria and peroxisomes as reflected in the reduced expressions of cpt1ab, hadhaa, cpt2, decr1, and acox1. These neurological and systemic metabolic adaptations serve to reduce energy expenditure, forming the basis of recessive evolution that eliminates nonessential morphological and behavioral traits and giving cavefish a selective advantage to thrive in caves where proper resource allocation becomes a major determinant of survival.

Tylvalosin demonstrates anti-parasitic activity and protects mice from acute toxoplasmosis.

AIMS: Toxoplasmosis, caused by Toxoplasma gondii (Tg), is one of the most prevalent zoonotic diseases worldwide. Currently, safe and efficient therapeutic options for this disease are still being developed, and are urgently needed. Tylvalosin (Tyl), a broad-spectrum third-generation macrolide, exhibits anti-bacterial, anti-viral, and anti-inflammatory properties. The present study aims to explore the anti-parasitic and immunomodulation activities of Tyl against Tg, and the underlying mechanism. MAIN METHODS: Adhesion, invasion, replication, proliferation, plaque, reversibility, immunofluorescence assays and transmission electron microscopy were utilized to determine the anti-Toxoplasma effect of Tyl. With acute toxoplasmosis model and rabies virus-induced brain inflammation model, the anti-toxoplasmosis and immunomodulation activities of Tyl were assessed by colorimetric assay, histopathological and Oil red O staining, and real-time quantitative PCR. The involved molecular mechanisms were investigated by western blotting and immunohistochemical staining. KEY FINDINGS: Tyl (5 and 10 µg/ml) can inhibit Tg propagation, and damage its ultrastructure irreversibly. The combination of Tyl and Pyrimethamine (Pyr) exhibits a better synergistic effect. Tyl (50 and 100 mg/kg) treatment intraperitoneally can delay mice death and improve survival rate, accompanying the reduced histopathological score and parasite load in the indicated tissues, espically for ileum, liver, spleen, lung and brain. Furthermore, Tg can modulate host phospho-p38 MAPK (pp38), subtilisin/kexin-isozyme-1 (SKI-1)-sterol regulatory element binding protein-1 (SREBP-1) (SKI-1-SREBP-1) pathway and peroxisome proliferators-activated receptor δ (PPARδ), while Tyl is able to reverse these signal pathways close to normal levels. SIGNIFICANCE: Our findings indicate that Tyl exhibits anti-Toxoplasma activity and protects mice from acute toxoplasmosis.

A dual-mode strategy combining SERS with MALDI FTICR MS based on core-shell silver nanoparticles for dye identification and semi-quantification in unearthed silks from Tang Dynasty.

Silk, as one of the representative artifacts of China, profoundly affects the communication between eastern and western civilizations, and dyes, as the color support of silks, reflected crucial historical, cultural and technological information. Surface enhanced Raman spectroscopy (SERS) characterized by vibrational information has been extensively employed in dye analysis. However, since natural plants with complex coloring compositions in ancient China were broadly applied in dying textiles, the existing SERS methods often misinterpret results in dye analysis. Besides, semi-quantification of each component was of great difficulty by SERS, limiting the exquisite comparative analyses of different historical samples. For the first time, a dual-mode strategy combining SERS with high mass resolution MALDI FTICR MS was developed in virtue of core-shell silver nanoparticles (AgNPs@PDA), which realized the precise identification and semi-quantification of complex dye mixtures, thus significantly improving the accuracy and applicability of traditional SERS method. Four typical dye components (alizarin, purpurin, berberine and indigo) have been identified and semi-quantified in unearthed dyed silks from Tang Dynasty based on the method. More interestingly, multiple dye components with different contents and their ratio could be precisely determined, which might help in further investigating their dyeing techniques. This dual-mode strategy represents a promising tool for providing solid support for cognition, evaluation and restoration of textile objects in museums and conservation centers.

Single-Vesicle Electrochemistry Reveals Sex Difference in Vesicular Storage and Release of Catecholamine.

Quantitative measurements of sex difference in vesicle chemistry (i.e., chemical storage and release) at the single-vesicle level are essential to understand sex differences in cognitive behaviors; however, such measurements are very challenging to conventional analytical methods. By using single-vesicle electrochemistry, we find the duration of single exocytotic events of chromaffin cells prepared from male rats is statistically longer than that from female rats, leading to more neurotransmitter released in the male group. Further analysis reveals that a higher percentage of vesicles in the female group release part of the neurotransmitter, i.e., partial release, during exocytosis than that in male group. This sex dimorphism in neurotransmitter release in exocytosis might relate to the sex difference in the expression of voltage-dependent calcium channels and membrane lipid composition. Our finding offers the first experimental evidence that sex dimorphism even exists in vesicle chemistry, providing a brand new viewpoint for understanding the sex dimorphism in exocytosis.

Design and Application of Near-Infrared Nanomaterial-Liposome Hybrid Nanocarriers for Cancer Photothermal Therapy.

Liposomes are attractive carriers for targeted and controlled drug delivery receiving increasing attention in cancer photothermal therapy. However, the field of creating near-infrared nanomaterial-liposome hybrid nanocarriers (NIRN-Lips) is relatively little understood. The hybrid nanocarriers combine the dual superiority of nanomaterials and liposomes, with more stable particles, enhanced photoluminescence, higher tumor permeability, better tumor-targeted drug delivery, stimulus-responsive drug release, and thus exhibiting better anti-tumor efficacy. Herein, this review covers the liposomes supported various types of near-infrared nanomaterials, including gold-based nanomaterials, carbon-based nanomaterials, and semiconductor quantum dots. Specifically, the NIRN-Lips are described in terms of their feature, synthesis, and drug-release mechanism. The design considerations of NIRN-Lips are highlighted. Further, we briefly introduced the photothermal conversion mechanism of NIRNs and the cell death mechanism induced by photothermal therapy. Subsequently, we provided a brief conclusion of NIRNs-Lips applied in cancer photothermal therapy. Finally, we discussed a synopsis of associated challenges and future perspectives for the applications of NIRN-Lips in cancer photothermal therapy.

An Integrated Transcriptomics and Proteomics Analysis Implicates lncRNA MALAT1 in the Regulation of Lipid Metabolism.

Long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is upregulated in various cancers, and its overexpression is associated with tumor growth and metastasis. MALAT1 has been recognized as a key player in the regulation of RNA splicing and transcription; however, the landscape of gene expression regulated by MALAT1 remains unclear. In this study, we employed an integrated transcriptomics and proteomics strategy to characterize the alterations in gene expression induced by MALAT1 knockdown in hepatocellular carcinoma (HCC) cells and identified 2662 differentially expressed transcripts and 1149 differentially expressed proteins. Interestingly, downregulation of MALAT1 reduced the abundances of multiple genes in the AMP-activated protein kinase (AMPK) signaling and biosynthesis of unsaturated fatty acids pathways. Further investigation showed that MALAT1 knockdown inhibited glucose uptake and lipogenesis by reducing the expression levels of these lipid metabolism related genes, which contributes to the oncogenic role of MALAT1 in tumor cell proliferation and invasion. This study uncovers the function of MALAT1 in the modulation of cancer lipid metabolism, reveals the underlying molecular mechanism, and further supports the potential therapeutic opportunities for targeting MALAT1 in HCC treatment.