Photothermal and ferroptosis synergistic therapy for liver cancer using iron-doped polydopamine nanozymes.

An innovative nanozyme, iron-doped polydopamine (Fe-PDA), which integrates iron ions into a PDA matrix, conferred peroxidase-mimetic activity and achieved a substantial photothermal conversion efficiency of 43.5 %. Fe-PDA mediated the catalysis of H2O2 to produce toxic hydroxyl radicals (•OH), thereby facilitating lipid peroxidation in tumour cells and inducing ferroptosis. Downregulation of solute carrier family 7 no. 11 (SLC7A11) and solute carrier family 3 no. 2 (SLC3A2) in System Xc- resulted in decreased intracellular glutathione (GSH) production and inactivation of the nuclear factor erythroid 2-related factor 2 (NRF2)-glutathione peroxidase 4 (GPX4) pathway, contributing to ferroptosis. Moreover, the application of photothermal therapy (PTT) enhanced the effectiveness of chemodynamic therapy (CDT), accelerating the Fenton reaction for targeted tumour eradication while sparing adjacent non-cancerous tissues. In vivo experiments revealed that Fe-PDA significantly hampered tumour progression in mice, emphasizing the potential of the dual-modality treatment combining CDT and PTT for future clinical oncology applications.

Two new species of the pseudoscorpion genus Stenohya (Pseudoscorpiones: Neobisiidae) from Guangxi Zhuang Autonomous Region, China.

Two new pseudoscorpion species, Stenohya dongtianensis sp. nov. and S. jiahensis sp. nov., from Guangxi Zhuang Autonomous Region, are described and illustrated. An identification key is provided for all known representatives of the genus Stenohya from China.

Synthesis, radiolabeling, and evaluation of a (4-quinolinoyl)glycyl-2-cyanopyrrolidine analogue for fibroblast activation protein (FAP) PET imaging.

Fibroblast activation protein (FAP) is regarded as a promising target for the diagnosis and treatment of tumors as it was overexpressed in cancer-associated fibroblasts. FAP inhibitors bearing a quinoline scaffold have been proven to show high affinity against FAP in vitro and in vivo, and the scaffold has been radio-labeled for the imaging and treatment of FAP-positive tumors. However, currently available FAP imaging agents both contain chelator groups to enable radio-metal labeling, making those tracers more hydrophilic and not suitable for the imaging of lesions in the brain. Herein, we report the synthesis, radio-labeling, and evaluation of a 18F-labeled quinoline analogue ([18F]3) as a potential FAP-targeted PET tracer, which holds the potential to be blood-brain barrier-permeable. [18F]3 was obtained by one-step radio-synthesis via a copper-mediated SNAR reaction from a corresponding boronic ester precursor. [18F]3 showed moderate lipophilicity with a log D 7.4 value of 1.11. In cell experiments, [18F]3 showed selective accumulation in A549-FAP and U87 cell lines and can be effectively blocked by the pre-treatment of a cold reference standard. Biodistribution studies indicated that [18F]3 was mainly excreted by hepatic clearance and urinary excretion, and it may be due to its moderate lipophilicity. In vivo PET imaging studies indicated [18F]3 showed selective accumulation in FAP-positive tumors, and specific binding was confirmed by blocking studies. However, low brain uptake was observed in biodistribution and PET imaging studies. Although our preliminary data indicated that [18F]3 holds the potential to be developed as a blood-brain barrier penetrable FAP-targeted PET tracer, its low brain uptake limits its application in the detection of brain lesions. Herein, we report the synthesis and evaluation of [18F]3 as a novel small-molecule FAPI-targeted PET tracer, and our results suggest further structural optimizations would be needed to develop a BBB-permeable PET tracer with this scaffold.

Formation pathways of aldehydes from heated cooking oils.

Cooking emissions account for a major fraction of urban volatile organic compounds and organic aerosol. Aldehyde species, in particular, are important exposure hazards in indoor residential and occupational environments, and precursors to particulate matter and ozone formation in outdoor air. Formation pathways of aldehydes from oils that lead to their emissions are not well understood. In this work, we investigate the underlying mechanisms involved in the formation of aldehydes from heated cooking oil emissions, through studying how antioxidants and oil composition modulate oxidation chemistry. Our results demonstrate that gaseous emissions are driven by radical-mediated autoxidation reactions in cooking oil, and the composition of cooking oils strongly influences the reaction mechanisms. Antioxidants have a dual effect on aldehyde emissions depending on the rates of radical propagation reactions. We propose a mechanistic framework that can be used to understand and predict cooking emissions under different cooking conditions. Our results highlight the need to understand the rates and mechanisms of autoxidation and other reactions in cooking oils in order to accurately predict the gas- and particle-phase emissions from food cooking in urban atmospheres.

Antioxidant and hypoglycemic activity of tea polysaccharides with different degrees of fermentation.

Four polysaccharides (GTPS, OTPS, BTPS and DTPS) were extracted from green tea, oolong tea, black tea and dark tea respectively. The physical and chemical properties, antioxidant and hypoglycemic activities were studied. Structural analysis showed that these tea polysaccharides were glycoprotein complexes, and there were significant differences in microstructure, protein, total sugar and uronic acid content. They were all composed of multiple monosaccharides and different molar ratios. In terms of antioxidant activity, completely fermented BTPS and DTPS had higher activity. Regarding to hypoglycemic effects, BTPS showed higher α-glucosidase inhibitory activity in vitro. And in the treatment of type 2 diabetes mice, Oral BTPS significantly controlled the levels of blood glucose, TG, TC, LDL-C, Cr, UREA, ALT and AST in diabetic mice, and improved insulin resistance. Histopathological observation further confirmed that BTPS can alleviate liver injury caused by hyperglycemia and hyperlipidemia. Data showed that BTPS significantly improved hyperglycemia and liver function in diabetic mice.

Positron emission tomography imaging of lung cancer: An overview of alternative positron emission tomography tracers beyond F18 fluorodeoxyglucose.

Lung cancer has been the leading cause of cancer-related mortality in China in recent decades. Positron emission tomography-computer tomography (PET/CT) has been established in the diagnosis of lung cancer. 18F-FDG is the most widely used PET tracer in foci diagnosis, tumor staging, treatment planning, and prognosis assessment by monitoring abnormally exuberant glucose metabolism in tumors. However, with the increasing knowledge on tumor heterogeneity and biological characteristics in lung cancer, a variety of novel radiotracers beyond 18F-FDG for PET imaging have been developed. For example, PET tracers that target cellular proliferation, amino acid metabolism and transportation, tumor hypoxia, angiogenesis, pulmonary NETs and other targets, such as tyrosine kinases and cancer-associated fibroblasts, have been reported, evaluated in animal models or under clinical investigations in recent years and play increasing roles in lung cancer diagnosis. Thus, we perform a comprehensive literature review of the radiopharmaceuticals and recent progress in PET tracers for the study of lung cancer biological characteristics beyond glucose metabolism.

In vivo PET Imaging of EGFR Expression: An Overview of Radiolabeled EGFR TKIs.

With the development of epidermal growth factor receptor (EGFR)-based tyrosine kinase inhibitors (TKIs) and their applications in the clinic, non-small-cell lung cancer (NSCLC) treatment has entered a new era, and a great number of patients have benefited. However, there still exist other subgroups of patients who may not benefit from EGFR TKIs, although EGFR mutation is the main driving mutation that leads to NSCLC. To identify potential NSCLC responders for TKI therapy and to detect EGFR status in vivo, noninvasive technology, such as TKI PET imaging, has been developed in recent years, and a great number of tyrosine kinase-targeted PET tracers have been reported. The visualization and quantification of EGFR expression in vivo by PET would provide the most important information for personalizing NSCLC therapy and prediction of response in clinical. This article reviews the progress of small molecular tyrosine kinase-targeted PET tracers and their applications in preclinical experiments and clinical studies. The current limitations and future development of these tracers are also briefly discussed.

Biogenic volatile organic compound emission patterns and secondary pollutant formation potentials of dominant greening trees in Chengdu, southwest China.

Integral to the urban ecosystem, greening trees provide many ecological benefits, but the active biogenic volatile organic compounds (BVOCs) they release contribute to the production of ozone and secondary organic aerosols, which harm ambient air quality. It is, therefore, necessary to understand the BVOC emission characteristics of dominant greening tree species and their relative contribution to secondary pollutants in various urban contexts. Consequently, this study utilized a dynamic enclosure system to collect BVOC samples of seven dominant greening tree species in urban Chengdu, Southwest China. Gas chromatography/mass spectrometry was used to analyze the BVOC components and standardized BVOC emission rates of each tree species were then calculated to assess their relative potential to form secondary pollutants. We found obvious differences in the composition of BVOCs emitted by each species. Ficus virens displayed a high isoprene emission rate at 31.472 µgC/(gdw (g dry weight)•hr), while Cinnamomum camphora emitted high volumes of D-Limonene at 93.574 µgC/(gdw•hr). In terms of the BVOC emission rates by leaf area, C. camphora had the highest emission rate of total BVOCs at 13,782.59 µgC/(m2•hr), followed by Cedrus deodara with 5466.86 µgC/(m2•hr). Ginkgo biloba and Osmanthus fragrans mainly emitted oxygenated VOCs with lower overall emission rates. The high BVOC emitters like F. virens, C. camphora, and Magnolia grandiflora have high potential for significantly contributing to environmental secondary pollutants, so should be cautiously considered for future planting. This study provides important implications for improving urban greening efforts for subtropical Chinese urban contexts, like Chengdu.

Synthesis, radiolabeling, and evaluation of a potent ß-site APP cleaving enzyme (BACE1) inhibitor for PET imaging of BACE1 in vivo.

The ß-site APP-cleaving enzyme 1 (BACE1) plays important roles in the proteolytic processing of amyloid precursor protein, and can be regarded as an important target for the diagnosis and treatment of AD. This study aimed to report the synthesis and evaluation of an 18F-labeled 2-amino-3,4-dihydroquinazoline analog as a potential BACE1 radioligand. A fluoropropyl side chain was introduced to the phenyl of this 3,4-dihydroquinazoline scaffold to generate the radioligand. Our preliminary data indicated that although the 2-amino-3,4-dihydroquinazoline scaffold possessed favorable in-vitro properties as a PET ligand, its poor brain uptake hindered the in-vivo imaging of BACE1. Further investigation would be required to optimize the scaffold for the development of a blood-brain-barrier-permeable BACE1-targeted PET ligand.

A polysaccharide from Lycium barbarum L.: Structure and protective effects against oxidative stress and high-glucose-induced apoptosis in ARPE-19 cells.

Lycium barbarum polysaccharides (LBPs) are beneficial for vision; however, relevant research has mainly focused on entire crude polysaccharides, with the basis and exact structure of the polysaccharide rarely explored. In this study, LICP009-3F-2a, a novel polysaccharide from Lycium barbarum L., was separated and then purified using anion-exchange and size-exclusion chromatography. Structural characteristics were investigated using chemical and spectroscopic methods, which revealed that LICP009-3F-2a has an Mw of 13720 Da and is an acidic heteropolysaccharide composed of rhamnose (39.1%), arabinose (7.4%), galactose (22.5%), glucose (8.3%), galacturonic acid (13.7%), and glucuronic acid (4.0%). Linkage and NMR data revealed that LICP009-3F-2a has the following backbone: →2)-α-L-Rha-(1 â†’ 2,4)-α-L-Rha-(1 â†’ 4)-α-D-GalAp-(1 â†’ 3,6)-ß-D-Galp-(1 â†’ 3,6)-ß-D-Galp-(1 â†’ 6)-ß-D-Galp-(1→, with three main branches, including: α-L-Araf-(1 â†’ 5)-α-L-Araf-(1 â†’ 6)-ß-D-Glcp-(1 â†’ 2,4)-α-L-Rha-(1→, ß-D-Glcp-(1 â†’ 4)-ß-D-Glcp-(1 â†’ 3,6)-ß-D-Galp-(1→, and ß-D-Galp-(1 â†’ 3)-ß-D-Galp-(1 â†’ 3,6)-ß-D-Galp-(1 â†’ . Differential scanning colorimetry and thermogravimetric analysis showed that LICP009-3F-2a is thermally stable, while X-ray diffractometry showed that LICP009-3F-2a has a semi-crystalline structure. In addition, LICP009-3F-2a protects ARPE-19 cells from H2O2-induced oxidative damage by regulating the expression of antioxidant SOD1 and CAT enzymes and down-regulating MMP2 expression. Moreover, LICP009-3F-2a promotes the proliferation of ARPE-19 cells in a concentration-dependent manner, and protects ARPE-19 cells from hyperglycemia by inhibiting apoptosis.

Five new troglobitic species of Tyrannochthonius (Arachnida, Pseudoscorpiones, Chthoniidae) from the Yunnan, Guizhou and Sichuan Provinces, China.

Five new species of the genus Tyrannochthonius Chamberlin, 1929 are described from caves in the provinces of Yunnan (T.huilongshanensis sp. nov., T.xinzhaiensis sp. nov., and T.yamuhensis sp. nov.), Guizhou (T.dongjiensis sp. nov.), and Sichuan (T.huaerensis sp. nov.). An identification key is provided for all known representatives of the genus Tyrannochthonius from China.

Cave-inhabiting Cheliferidae (Arachnida, Pseudoscorpiones) from Thailand, with description of four new species of Metachelifer Redikorzev.

Four new species of the genus Metachelifer Redikorzev, 1938 are described from caves in the provinces of Tak (M.takensis sp. nov. and M.thailandicus sp. nov.), Chiangmai (M.mahnerti sp. nov.), and Nakhon Ratchasima (M.cheni sp. nov.). An identification key is provided to all known world representatives of the genus Metachelifer.

A report of the complete mitochondrial genome of Bisetocreagris titanium (Arachnida: Pseudoscorpiones: Neobisiidae) from Yunnan Province, China.

A complete mitogenome of a cave dwelling pseudoscorpion Bisetocreagris titanium is reported here. The mitogenome is a circular DNA molecule with a length of 14,756 base pairs (bp), and it contains 13 protein coding genes (PCGs), 22 transfer RNAs (tRNAs), 2 ribosomal RNAs (rRNAs), and 1 putative control region. Phylogenetic analysis of 30 Arachnida species was performed based on the amino acid datasets of 13 PCGs, and the result indicated Pseudoscorpiones is the sister lineage of Acariformes. This result is congruent with the former phylogenetic results of mitogenomes, but incongruent with the results of morphological characters and/or ribosomal DNA data that indicated Pseudoscorpiones are positioned in a clade with the Solifugae.

Antibacterial activity of ZnO quantum dots and its protective effects of chicks infected withSalmonella pullorum.

In light of emerging antibiotic resistance, synthesis of active, environmental friendly antimicrobial alternatives becomes increasingly necessary. In this study, ZnO quantum dots (ZnO QDs) were developed by the sol-gel method and characterized. The antibacterial activities of ZnO QDs againstEscherichia coli(E. coli),Staphylococcus aureus(S. aureus) andSalmonella Pullorum(S. Pullorum) were systematically investigated. Moreover, the protective effects of ZnO QDs on Salmonella-caused pullorosis in chicks were also explored. The results indicated that the size range of ZnO QDs was 3-6 nm. Antibacterial results showed that ZnO QDs treatment inhibited the growth ofE. coli,S. aureus, andS. Pullorumin the rate of 87.06 ± 0.98%, 94.75 ± 2.28%, and 85.55 ± 1.15%, respectively. Its excellent antibacterial property was manifested with the minimum inhibitory concentration of 0.7812, 0.0976, and 0.1953 mg ml-1, which may be attributed to the production of reactive oxygen species, the dissolution of Zn2+ions, and the loss of cell integrity. Furthermore, in thein vivotest, the ZnO QDs effectively reduced the mortality of chicks infected withS. Pullorumvia regulating the balance of the intestinal flora, protecting liver and intestine, and modulating the balance of antioxidation systems. This study reveals that ZnO QDs exerts remarkably antibacterial activityin vitroand anti-pullorosis effect in chicks.

Artificial light reduces foraging opportunities in wild least horseshoe bats.

Artificial light at night has been proposed as a global threat to biodiversity. Insectivorous bats are strictly nocturnal animals that are vulnerable to disruption from artificial light. Given that many light-sensitive bats tend to avoid night light during roost departure, it is often assumed that nighttime light pollution reduces their foraging opportunities, albeit empirical evidence in support of this hypothesis remains elusive. Here, we used least horseshoe bats, Rhinolophus pusillus, to assess whether white artificial light is detrimental for the opportunities of foraging. We manipulated the levels of ambient illumination and perceived predation risk inside the bat roost. We monitored bats' emergence activity using high-speed video and audio recording systems. DNA-based faecal dietary analysis and insect survey were applied to determine activity time of prey in foraging areas. Following experimentally manipulation of white light-emitting diode (LED) lighting 0-15 min after sunset, bat pass, flight duration, and echolocation pulse emission decreased. The mean emergence time of bats flying out was delayed by 14 min under lit treatment compared with the dark control. Only 10% of bats left for foraging during 40 min of light exposure. Aversive effects of LED light on bat emergence were robust regardless of the presence of a potential predator. Insect prey reached a peak of abundance between 30 and 60 min after sunset. These results demonstrate that white artificial light hinders evening emergence behavior in least horseshoe bats, leading to a mismatch between foraging onset and peak food availability. Our findings highlight that light pollution overrides foraging onset, suggesting the importance of improving artificial lighting scheme near the roosts of light-sensitive bats.

Glucose oxidase-mediated tumor starvation therapy combined with photothermal therapy for colon cancer.

Colon cancer is one of the most common cancers with high mortality, and can easily spread and metastasize, remaining an urgent disease to be solved. Nanomaterial-associated starvation or photothermal therapy has been considered to be a promising strategy in tumor therapy. However, the therapeutic effect of a single regimen for cancer treatment still needs to be improved due to their respective limitations. Herein, a biomimetic multifunctional nanoreactor is developed by encapsulating glucose oxidase and gold nanorods (AuNRs) in an erythrocyte membrane camouflaged metal-organic framework (MOF) nanoparticle (ZGAM), which was exploited for synergistic treatment of colon cancer by combining glucose oxidase-based starvation with AuNR-based photothermal therapy (PTT). This biomimetic nanoreactor could not only exhaust endogenous glucose to suppress the growth of the tumor by the released glucose oxidase (GOx), but also enhance the effect of photothermal therapy via inhibiting the expression of heat shock protein (HSP). In vitro and in vivo investigations indicate that this biomimetic nanoreactor shows excellent therapeutic effects on tumors, resulting from the synergistic treatment of starvation therapy and PTT. Therefore, the proposed strategy may open a window to develop an intelligent therapeutic system for better therapeutic efficacy against cancer.

The Therapeutic Potential of Purinergic Receptors in Alzheimer's Disease and Promising Therapeutic Modulators.

Recent studies have proven that the purinergic signaling pathway plays a key role in neurotransmission and neuromodulation, and is involved in various neurodegenerative diseases and psychiatric disorders. With the characterization of the subtypes of receptors in purinergic signaling, i.e. the P1 (adenosine), P2X (ion channel) and P2Y (G protein-coupled), more attention has been paid to the pathophysiology and therapeutic potential of purinergic signaling in the central nervous system disorders. Alzheimer's disease (AD) is a progressive and deadly neurodegenerative disease that is characterized by memory loss, cognitive impairment and dementia. However, as drug development aimed to prevent or control AD has series of failures in recent years, more researchers have focused on the neuroprotection-related mechanisms such as purinergic signaling in AD patients to find a potential cure. This article reviews the recent discoveries of purinergic signaling in AD, and summarizes the potential agents as modulators for the receptors of purinergic signaling in AD-related research and treatments. Thus, our paper provides an insight into purinergic signaling in the development of anti- AD therapies.

miR­378 in combination with ultrasonic irradiation and SonoVue microbubbles transfection inhibits hepatoma cell growth.

Ultrasonic microbubbles in combination with microRNA (miRNAs/miRs) exhibited promising effects on cancer treatments. The aim was to investigate the role of miR­378 in hepatoma cells and the efficiency of it in combination with ultrasonic irradiation and SonoVue® microbubbles method for cell transfection. HuH­7, Hep3B and SK­Hep1 cells were transfected with an miR­378 mimic using only Lipofectamine® 3000 or combined with SonoVue microbubbles and ultrasonic irradiation at 0.5 W/cm2 for 30 sec. mRNAs and protein levels of Cyclin D1, Bcl­2, Bax, Akt, p53 and Survivin were detected by reverse transcription­quantitative PCR and western blotting, respectively. Cell survival rate, proliferation, cell cycle and apoptosis were determined by Cell Counting Kit­8, cell double cytochemical staining and flow cytometry, respectively. It was found that using a combination of ultrasonic irradiation and the SonoVue microbubbles method increased the effectiveness of miR­378 transfection into hepatocellular carcinoma (HCC) cells, and increased the inhibition of cell survival and proliferation. Moreover, miR­378 increased the rate of apoptosis and upregulated the expression of Bax and p53, and suppressed the cell cycle and downregulated the expression of Cyclin D1, Bcl­2, Akt, ß­catenin and Survivin much more effectively in the HCC cell line by applying the combined method. Thus, miR­378 was shown to be a suppressive factor to reduce proliferation and increase apoptosis in HCC cells. Additionally, the combination of ultrasonic irradiation and SonoVue microbubbles method was more efficient in the transfection of miRNA.

A new cave-dwelling species of Lagynochthonius (Arachnida: Pseudoscorpiones: Chthoniidae) from Yunnan Province, China.

A new pseudoscorpion, Lagynochthonius bailongtanensis sp. nov., is described and illustrated from specimens collected in a cave in Luoping County, Yunnan Province, China. This species is notable in being strongly troglomorphic. A new identification key is provided to all known Chinese representatives of the genus Lagynochthonius.

Small Molecule Natural Products and Alzheimer's Disease.

Alzheimer's disease (AD) is a progressive and deadly neurodegenerative disease that is characterized by memory loss, cognitive impairment and dementia. Several hypotheses have been proposed for the pathogenesis based on the pathological changes in the brain of AD patients during the last few decades. Unfortunately, there is no effective agents/therapies to prevent or control AD at present. Currently, only a few drugs, which function as acetylcholinesterase (AChE) inhibitors or N-methyl-Daspartate (NMDA) receptor antagonists, are available to alleviate symptoms. Since many small molecule natural products have shown their functions as agonists or antagonists of receptors, as well as inhibitors of enzymes and proteins in the brain during the development of central nervous system (CNS) drugs, it is likely that natural products will play an important role in anti-AD drug development. We review recent papers on using small molecule natural products as drug candidates for the treatment of AD. These natural products possess antioxidant, anti-inflammatory, anticholinesterase, anti-amyloidogenic and neuroprotective activities. Moreover, bioactive natural products intended to be used for preventing AD, reducing the symptoms of AD and the new targets for treatment of AD are summarized.