Ru(II) Oligothienyl Complexes with Fluorinated Ligands: Photophysical, Electrochemical, and Photobiological Properties.

A series of Ru(II) complexes incorporating two 4,4'-bis(trifluoromethyl)-2,2'-bipyridine (4,4'-btfmb) coligands and thienyl-appended imidazo[4,5-f][1,10]phenanthroline (IP-nT) ligands was characterized and assessed for phototherapy effects toward cancer cells. The [Ru(4,4'-btfmb)2(IP-nT)]2+ scaffold has greater overall redox activity compared to Ru(II) polypyridyl complexes such as [Ru(bpy)3]2+. Ru-1T-Ru-4T have additional oxidations due to the nT group and additional reductions due to the 4,4'-btfmb ligands. Ru-2T-Ru-4T also exhibit nT-based reductions. Ru-4T exhibits two oxidations and eight reductions within the potential window of -3 to +1.5 V. The lowest-lying triplets (T1) for Ru-0T-2T are metal-to-ligand charge-transfer (3MLCT) excited states with lifetimes around 1 µs, whereas T1 for Ru-3T-4T is longer-lived (∼20-24 µs) and of significant intraligand charge-transfer (3ILCT) character. Phototoxicity toward melanoma cells (SK-MEL-28) increases with n, with Ru-4T having a visible EC50 value as low as 9 nM and PI as large as 12,000. Ru-3T and Ru-4T retain some of this activity in hypoxia, where Ru-4T has a visible EC50 as low as 35 nM and PI as high as 2900. Activity over six biological replicates is consistent and within an order of magnitude. These results demonstrate the importance of lowest-lying 3ILCT states for phototoxicity and maintaining activity in hypoxia.

BaTiO3 Catalyzed Ultrasonic Driven Piezoelectric Induced Reversible Addition-Fragmentation Chain-Transfer Polymerization in Aqueous Media.

Compared with normal stimulus such as light and heat, ultrasonic possesses much deeper penetration into tissues and organs and has lower scattering in heterogeneous systems as a noninvasive stimulus. Reversible addition-fragmentation chain-transfer polymerization (RAFT) in aqueous media w a s performed in a commercial ultrasonic wash bath with 40 kHz frequency ultrasonic, in the presence of piezoelectric tetragonal BaTiO3 (BTO) nanoparticles. Owing to the electron transfer from BTO under the ultrasonic action, the water could be decomposed to produce hydroxyl radical (HO•) and initiated the RAFT polymerization (Piezo-RAFT). The Piezo-RAFT polymerization exhibited features of controllable and livingness, such as linear increase of molar mass and narrow molar mass distributions (Mw/Mn<1.20). Excellent temporal control of the polymerization and the chain fidelity of polymers w e r e illustrated by "ON and OFF" experiment and chain extension, separately. Moreover, this ultrasonic driven piezoelectric induced RAFT polymerization in aqueous media can be directly used for the preparation of piezoelectric hydrogel which have potential application for stress sensor. This article is protected by copyright. All rights reserved.

An approach based on a combination of toxicological experiments and in silico predictions to investigate the adverse outcome pathway (AOP) of paraquat neuro-immunotoxicity.

Paraquat (PQ) exposure is strongly associated with neurotoxicity. However, research on the neurotoxicity mechanisms of PQ varies in terms of endpoints of toxic assessment, resulting in a great challenge to understand the early neurotoxic effects of PQ. In this study, we developed an adverse outcome pathway (AOP) to investigate PQ-induced neuro-immunotoxicity from an immunological perspective, combining of traditional toxicology methods and computer simulations. In vivo, PQ can microstructurally lead to an early synaptic loss in the brain mice, which is a large degree regarded as a main reason for cognitive impairment to mice behavior. Both in vitro and in vivo demonstrated synapse loss is caused by excessive activation of the complement C1q/C3-CD11b pathway, which mediates microglial phagocytosis dysfunction. Additionally, the interaction between PQ and C1q was validated by molecular simulation docking. Our findings extend the AOP framework related to PQ neurotoxicity from a neuro-immunotoxic perspective, highlighting C1q activation as the initiating event for PQ-induced neuro-immunotoxicity. In addition, downstream complement cascades induce abnormal microglial phagocytosis, resulting in reduced synaptic density and subsequent non-motor dysfunction. These findings deepen our understanding of neurotoxicity and provide a theoretical basis for ecological risk assessment of PQ.

Predicting drug-Protein interaction with deep learning framework for molecular graphs and sequences: Potential candidates against SAR-CoV-2.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the COVID-19 disease, which represents a new life-threatening disaster. Regarding viral infection, many therapeutics have been investigated to alleviate the epidemiology such as vaccines and receptor decoys. However, the continuous mutating coronavirus, especially the variants of Delta and Omicron, are tended to invalidate the therapeutic biological product. Thus, it is necessary to develop molecular entities as broad-spectrum antiviral drugs. Coronavirus replication is controlled by the viral 3-chymotrypsin-like cysteine protease (3CLpro) enzyme, which is required for the virus's life cycle. In the cases of severe acute respiratory syndrome coronavirus (SARS-CoV) and middle east respiratory syndrome coronavirus (MERS-CoV), 3CLpro has been shown to be a promising therapeutic development target. Here we proposed an attention-based deep learning framework for molecular graphs and sequences, training from the BindingDB 3CLpro dataset (114,555 compounds). After construction of such model, we conducted large-scale screening the in vivo/vitro dataset (276,003 compounds) from Zinc Database and visualize the candidate compounds with attention score. geometric-based affinity prediction was employed for validation. Finally, we established a 3CLpro-specific deep learning framework, namely GraphDPI-3CL (AUROC: 0.958) achieved superior performance beyond the existing state of the art model and discovered 10 molecules with a high binding affinity of 3CLpro and superior binding mode.

Confined Unimolecular Micelles for Directed Self-Assembly of Ultrastable Multiple-Responsive Ratiometric Fluorescent Ultrasmall Nanoparticle Assemblies.

Ultrasmall fluorescent nanomaterials have been widely studied as novel fluorescent probes; however, these nanomaterials are prone to structural damage or aggregation, and the sensitivity and accuracy of most single emission fluorescence probes were very low. Therefore, the controlled synthesis of stable dual-emission ratiometric fluorescence ultrasmall assembly probes still remains a challenge. Herein, star-like polymer unimolecular micelles were utilized as a scaffold template to encapsulate fluorescent ultrasmall carbon quantum dots (CQDs) and gold nanoclusters (AuNCs) via the polymer template directed self-assembly strategy to obtain multiple-responsive ratiometric fluorescent assemblies. The assemblies were ultrastable, well-defined, and nearly monodispersed with controlled size, regular morphology, and pH- and thermal-responsiveness. The assemblies can be applied to realize rapid, sensitive, quantitative, and specific detection of Cu2+ and GSH. Moreover, the convenient rapid real-time detection was realized via the combination of the visualized paper-based sensor, and the multilevel information encryption was also achieved.

A double-network porous hydrogel based on high internal phase emulsions as a vehicle for potassium sucrose octasulfate delivery accelerates diabetic wound healing.

Diabetic wounds are a difficult medical challenge. Excessive secretion of matrix metalloproteinase-9 (MMP-9) in diabetic wounds further degrades the extracellular matrix and growth factors and causes severe vascular damage, which seriously hinders diabetic wound healing. To solve these issues, a double-network porous hydrogel composed of poly (methyl methacrylate-co-acrylamide) (p(MMA-co-AM)) and polyvinyl alcohol (PVA) was constructed by the high internal phase emulsion (HIPE) technique for the delivery of potassium sucrose octasulfate (PSO), a drug that can inhibit MMPs, increase angiogenesis and improve microcirculation. The hydrogel possessed a typical polyHIPE hierarchical microstructure with interconnected porous morphologies, high porosity, high specific surface area, excellent mechanical properties and suitable swelling properties. Meanwhile, the p(MMA-co-AM)/PVA@PSO hydrogel showed high drug-loading performance and effective PSO release. In addition, both in vitro and in vivo studies showed that the p(MMA-co-AM)/PVA@PSO hydrogel had good biocompatibility and significantly accelerated diabetic wound healing by inhibiting excessive MMP-9 in diabetic wounds, increasing growth factor secretion, improving vascularization, increasing collagen deposition and promoting re-epithelialization. Therefore, this study provided a reliable therapeutic strategy for diabetic wound healing, some theoretical basis and new insights for the rational design and preparation of wound hydrogel dressings with high porosity, high drug-loading performance and excellent mechanical properties.

Carbon Fiber Film with Multi-Hollow Channels to Expedite Oxygen Electrocatalytic Reaction Kinetics for Flexible Zn-Air Battery.

The high oxygen electrocatalytic overpotential of flexible cathodes due to sluggish reaction kinetics result in low energy conversion efficiency of wearable zinc-air batteries (ZABs). Herein, lignin, as a 3D flexible carbon-rich macromolecule, is employed for partial replacement of polyacrylonitrile and constructing flexible freestanding air electrodes (FFAEs) with large amount of mesopores and multi-hollow channels via electrospinning combined with annealing strategy. The presence of lignin with disordered structure decreases the graphitization of carbon fibers, increases the structural defects, and optimizes the pore structure, facilitating the enhancement of electron-transfer kinetics. This unique structure effectively improves the accessibility of graphitic-N/pyridinic-N with oxygen reduction reaction (ORR) activity and pyridinic-N with oxygen evolution reaction (OER) activity for FFAEs, accelerating the mass transfer process of oxygen-active species. The resulting N-doped hollow carbon fiber films (NHCFs) exhibit superior bifunctional ORR/OER performance with a low potential difference of only 0.60 V. The rechargeable ZABs with NHCFs as metal-free cathodes possess a long-term cycling stability. Furthermore, the NHCFs can be used as FFAEs for flexible ZABs which have a high specific capacity and good cycling stability under different bending states. This work paves the way to design and produce highly active metal-free bifunctional FFAEs for electrochemical energy devices.

Enhancing Security in Visible Light Communication: A Tabu-Search-Based Method for Transmitter Selection.

In this paper, we explore the secrecy performance of a visible light communication (VLC) system consisting of distributed light-emitting diodes (LEDs) and multiple users (UEs) randomly positioned within an indoor environment while considering the presence of an eavesdropper. To enhance the confidentiality of the system, we formulate a problem of maximizing the sum secrecy rate for UEs by searching for an optimal LED for each UE. Due to the non-convex and non-continuous nature of this security maximization problem, we propose an LED selection algorithm based on tabu search to avoid getting trapped in local optima and expedite the search process by managing trial vectors from previous iterations. Moreover, we introduce three LED selection strategies with a low computational complexity. The simulation results demonstrate that the proposed algorithm achieves a secrecy performance very close to the global optimal value, with a gap of less than 1%. Additionally, the proposed strategies exhibit a performance gap of 28% compared to the global optimal.

Bioinspired wet adhesive carboxymethyl cellulose-based hydrogel with rapid shape adaptability and antioxidant activity for diabetic wound repair.

Currently, adhesive hydrogels have shown promising effect in chronic diabetic wound repair. However, there are issues and challenges in treating diabetic wounds due to inadequate wet adhesion, unable to fill irregular and deep wounds, and oxidative stress. Herein, a mussel-inspired naturally hydrogel dressing with rapid shape adaptability, wet adhesion and antioxidant abilities for irregular, deep and frequently movement diabetic wounds repair was constructed by comprising catechol modified carboxymethyl cellulose (CMC-DA) and tannic acid. Benefiting from the reversible hydrogen bonding, the resulting hydrogels exhibited injectability, remarkable self-healing ability, rapid shape adaptability and strong tissue adhesion (45.9 kPa), thereby contributing to self-adaptive irregular-shaped wounds or moving joint parts. Especially, the adhesion strength of the hydrogel on wet tissue still remained at 14.9 kPa. Besides, the hydrogels could be easily detached from the skin by ice-cooling that avoided secondary damage caused by dressing change. Remarkably, the hydrogels possessed excellent antioxidant, satisfactory biocompatibility, efficient hemostasis and antibacterial properties. The in vivo evaluation further demonstrated that the hydrogel possessed considerable wound-healing promotion effect by regulating diabetic microenvironment, attributed to that the hydrogel could significantly reduce inflammatory response, alleviate oxidative stress and regulate neovascularization. Overall, this biosafe adhesive hydrogel had great potentials for diabetic wound management.

A potential mechanism clue to the periodic storm from microglia activation and progressive neuron damage induced by paraquat exposure.

Paraquat (PQ), is characterized by neurotoxicity, which increases the potential risk of Parkinson's disease (PD) exposure in the long-term and low doses. Triggering microglia activation and neuroinflammation is deemed an early event resulting in PD. However, the underlying pathogenesis of PD by PQ is not clear yet. In this article, C57BL/6J mice treated with PQ could successfully act out Parkinson-like. In addition, we observed the fluorescence intensity enhancement of Iba-1 activated microglia with released pro-inflammatory, all ahead of both the damage of dopaminergic neurons in the substantia nigra and corpus striatum of the brain. Surprisingly, the injection of minocycline before PQ for many hours not only can effectively improve the neurobehavioral symptoms of mice but inhibit the activation of microglia and the release of pro-inflammatory substances, even controlling the gradual damage and loss of neurons. A further mechanism of minocycline hampered the expression levels of key signaling proteins PI3K, PDK1, p-AKT, and CD11b (the receptor of microglia membrane recognition), while a large number of inflammatory factors. Our results suggested that the CD11b/PI3K/NOX2 pathway may be a clue that microglia-mediated inflammatory responses and neuronal damage in a PQ-induced abnormal behavior Parkinson-like mouse.

Combatting ageing in dermal papilla cells and promoting hair follicle regeneration using exosomes from human hair follicle dermal sheath cup cells.

Dermal papilla cells (DPCs) undergo premature ageing in androgenetic alopecia and senescent alopecia. As critical components of hair follicle reconstruction, DPCs are also prone to senescence in vitro, resulting in a diminished hair follicle inductivity capacity. Dermal sheath cup cells (DSCCs), a specific subset of hair follicle mesenchymal stem cells, intimately linked to the function of DPCs. The primary objective of this research is to investigate the anti-ageing effect of exosomes derived from DSCCs (ExoDSCCs ) on DPCs. Exosomes were utilized to treat H2 O2 -induced DPCs or long-generation DPCs(P10). Our findings demonstrate that ExoDSCCs(P3) promote the proliferation, viability and migration of senescent DPCs while inhibiting cell apoptosis. The expression of senescence marker SA-ß-Gal were significantly downregulated in senescent DPCs. When treated with ExoDSCCs(P3) , expression of inducibility related markers alkaline phosphatase and Versican were significantly upregulated. Additionally, ExoDSCCs(P3) activated the Wnt/ß-catenin signalling in vitro. In patch assay, ExoDSCCs(P3) significantly promoted hair follicle reconstruction in senescent DPCs. In summary, our work highlights that ExoDSCCs(P3) may restore the biological functions and improve the hair follicle induction ability of senescent DPCs. Therefore, ExoDSCCs(P3) may represent a new strategy for intervening in the ageing process of DPCs, contributing to the prevention of senile alopecia.

Systematic review of the risk of urolithiasis following parathyroidectomy in patients with primary hyperparathyroidism.

OBJECTIVE: Parathyroidectomy (PTX) is the conclusive therapy for primary hyperparathyroidism (PHPT), but its effect on the risk of urolithiasis is inconclusive. We comprehensively reviewed the currently available research to investigate the impact of PTX on the likelihood of urolithiasis among individuals suffering PHPT. METHODS: Internet-based articles in English language released on Cochrane, PubMed, Scopus, Web of knowledge, and Embase up to September, 2023 were comprehensively reviewed. Each publication in contrast to the incidence, occurrence, or recurrence of urolithiasis after PTX versus medical treatment in PHPT patients was included. The outcome with pooled relative risks (RRs) and corresponding 95% confidence intervals (CIs) was examined employing DerSimonian and Laird's model of random effects. To determine the range of the real effect size of a future study in 95% of all populations, a prediction interval (PI) was also established. RESULTS: Finally, ten studies involving 74,190 patients were included. Results from randomized-controlled trials (RCTs) and observational studies (OSs) both revealed that PTX did not substantially lessen the vulnerability of urolithiasis among individuals with PHPT (RCTs: pooled relative risk [RR] 0.42, 95%CI 0.13-1.41, p = 0.163; OSs: pooled RR 1.37, 95%CI 0.96 to 1.97, p = 0.084). The PI (RCT: 0.03 to 5.96; OSs: 0.44-4.20) containing 1.0 suggested the possibility of consistent results in future studies. Subgroup and sensitivity analyses supported the above findings, and no evidence showed publication bias. CONCLUSION: Our analysis from the available RCTs or OSs did not give adequate or exact proof that the average effect of PTX lowers the incidence of urolithiasis among PHPT persons based on the random-effects model. Future research shall take into account the common effect of PTX as well as the prerequisites of preventive stone procedures, which will further help us assess the effectiveness of PTX in reducing kidney calculus comorbidity and develop techniques to avoid stone sequelae in these individuals.

Building Your Future Holographic Mentor: Can We Use Mixed Reality Holograms for Visual Spatial Motor Skills Acquisition in Surgical Education?

Learning surgical skills require critical visual-spatial motor skills. Current learning methods employ costly and limited in-person teaching in addition to supplementation by videos, textbooks, and cadaveric labs. Increasingly limited healthcare resources and in-person training has led to growing concerns for skills acquisition of trainees. Recent Mixed Reality (MR) devices offer an attractive solution to these resource barriers by providing three-dimensional holographic representations of reality that mimic in-person experiences in a portable, individualized, and cost-effective form. We developed and evaluated two holographic MR models to explore the feasibility of visual-spatial motor skill acquisition from a technical development, learning, and usability perspective. In our first, a pair of holographic hands were created and projected in front of the trainee, and participants were evaluated on their ability to learn complex hand motions in comparison to traditional methods of video and apprenticeship-based learning. The second model displayed a 3D holographic model of the middle and inner ear with labeled anatomical structures which users could explore and user experience feedback was obtained. Our studies demonstrated that scores between MR and apprenticeship learning were comparable. All felt MR was an effective learning tool and most noted that the MR models were better than existing didactic methods of learning. Identified advantages of MR included the ability to provide true 3D spatial representation, improved visualization of smaller structures in detail by upscaling the models, and improved interactivity. Our results demonstrate that holographic learning is able to mimic in-person learning for visual-spatial motor skills and could be a new effective form of self-directed apprenticeship learning.

Enhanced TARP-γ8-PSD-95 coupling in excitatory neurons contributes to the rapid antidepressant-like action of ketamine in male mice.

Ketamine produces rapid antidepressant effects at sub-anesthetic dosage through early and sustained activation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs), however, the exact molecular mechanism still remains unclear. Transmembrane AMPAR regulatory protein-γ8 (TARP-γ8) is identified as one of AMPAR auxiliary subunits, which controls assemblies, surface trafficking and gating of AMPARs. Here, we show that ketamine rescues both depressive-like behaviors and the decreased AMPARs-mediated neurotransmission by recruitment of TARP-γ8 at the postsynaptic sites in the ventral hippocampus of stressed male mice. Furthermore, the rapid antidepressant effects of ketamine are abolished by selective blockade of TARP-γ8-containing AMPAR or uncoupling of TARP-γ8 from PSD-95. Overexpression of TARP-γ8 reverses chronic stress-induced depressive-like behaviors and attenuation of AMPARs-mediated neurotransmission. Conversely, knockdown of TARP-γ8 in excitatory neurons prevents the rapid antidepressant effects of ketamine.

Ru(II) Phenanthroline-Based Oligothienyl Complexes as Phototherapy Agents.

Ru(II) polypyridyl complexes have gained widespread attention as photosensitizers for photodynamic therapy (PDT). Herein, we systematically investigate a series of the type [Ru(phen)2(IP-nT)]2+, featuring 1,10-phenanthroline (phen) coligands and imidazo[4,5-f][1,10]phenanthroline ligands tethered to n = 0-4 thiophene rings (IP-nT). The complexes were characterized and investigated for their electrochemical, spectroscopic, and (photo)biological properties. The electrochemical oxidation of the nT unit shifted by -350 mV as n = 1 → 4 (+920 mV for Ru-1T, +570 mV for Ru-4T); nT reductions were observed in complexes Ru-3T (-2530 mV) and Ru-4T (-2300 mV). Singlet oxygen quantum yields ranged from 0.53 to 0.88, with Ru-3T and Ru-4T being equally efficient (∼0.88). Time-resolved absorption spectra of Ru-0T-1T were dominated by metal-to-ligand charge-transfer (3MLCT) states (τTA = 0.40-0.85 µs), but long-lived intraligand charge-transfer (3ILCT) states were observed in Ru-2T-4T (τTA = 25-148 µs). The 3ILCT energies of Ru-3T and Ru-4T were computed to be 1.6 and 1.4 eV, respectively. The phototherapeutic efficacy against melanoma cells (SK-MEL-28) under broad-band visible light (400-700 nm) increases as n = 0 → 4: Ru-0T was inactive up to 300 µM, Ru-1T-2T were moderately active (EC50 ∼ 600 nM, PI = 200), and Ru-3T (EC50 = 57 nM, PI > 1100) and Ru-4T (EC50 = 740 pM, PI = 114,000) were the most phototoxic. The activity diminishes with longer wavelengths of light and is completely suppressed for all complexes except Ru-3T and Ru-4T in hypoxia. Ru-4T is the more potent and robust PS in 1% O2 over seven biological replicates (avg EC50 = 1.3 µM, avg PI = 985). Ru-3T exhibited hypoxic activity in five of seven replicates, underscoring the need for biological replicates in compound evaluation. Singlet oxygen sensitization is likely responsible for phototoxic effects of the compounds in normoxia, but the presence of redox-active excited states may facilitate additional photoactive pathways for complexes with three or more thienyl groups. The 3ILCT state with its extended lifetime (30-40× longer than the 3MLCT state for Ru-3T and Ru-4T) implicates its predominant role in photocytotoxicity.

Emodin exhibits anti-acne potential by inhibiting cell growth, lipogenesis, and inflammation in human SZ95 sebocytes.

Emodin, a natural anthraquinone derivative, possesses anti-proliferative and anti-inflammatory properties in skin diseases. However, little information is available on the efficacy of emodin in treating acne vulgaris (acne). This study aims to investigate the protective effects and potential mechanisms of emodin as an anti-acne agent. In vitro, SZ95 sebocytes was chose to establish an acneigenic cellular model. We found that emodin effectively inhibited proliferation, induced cell cycle arrest and apoptosis of SZ95 sebocytes in a dose-dependent manner. To evaluate the lipid-lowering potential of emodin, we examined the levels of lipid contents and lipogenic transcription factors, and found that both lipid production and protein expression of PPARγ, LXR α/ß, and SREBP-1 were decreased after treatment with emodin. Furthermore, our results revealed that emodin inhibited sebaceous lipogenesis induced by insulin-like growth factor 1 (IGF-1), which was accompanied by a potent inhibition of the phosphoinositide-3-kinase (PI3K)/Akt/forkhead box protein O1 (FoxO1) pathway. In detail, emodin augmented the inhibitory effect of isotretinoin and PI3K inhibitor LY294002, while attenuating the activation of IGF-1 on PI3K/Akt/FoxO1 pathway. In addition, emodin could decrease the secretion of pro-inflammatory cytokines IL-6 and IL-8, and suppress the expression of NLRP3, capase-1, IL-1ß, and IL-18 in SZ95 sebocytes exposed to Cutibacterium acnes. Overall, our study provides preliminary evidence supporting the anti-growth, anti-lipogenic and anti-inflammatory properties of emodin, indicating the potential therapeutic application of emodin for acne treatment.

Chiral Confined Unimolecular Micelles for Controlled In Situ Fabrication of Optically Active Hybrid Nanostructures.

Functional nanomaterials made by chiral induction have attracted extensive attention because of their intriguing characteristics and potential applications. However, the precise and controllable fabrication of chiral nanomaterials still remains challenging but is highly desired. In this study, chiral unimolecular micelles with different molecular weights and chiroptical activities were prepared by photoinduced atom transfer radical polymerization (photoATRP). Through nanoconfined growth, the chiral plasmonic nanoparticle assemblies with predesigned size and morphology were prepared using chiral unimolecular micelles as nanoreactors. The controllability over chiral assemblies and the size effect on chiroptical properties were also investigated. Furthermore, chiral complexes with absorption asymmetry and circularly polarized luminescence (glum = 4.25 × 10-4) were easily constructed via mixing of organic fluorescent molecules and chiral templates based on intermolecular hydrogen bonds. Such results indicated that our unimolecular-micelle-based templates enable the controllable preparation of both inorganic and organic chiral nanostructures with tailored dimensions, sizes, compositions, and optical activities.

[Determination of furosine in liquid milk by high performance liquid chromatography-quadrupole time-of-flight mass spectrometry].

Furosine is often used both domestically and internationally as an indicator of the degree of heating to evaluate milk quality. However, in actual detection, the complexity of the milk matrix may lead to the inaccurate quantification of furosine in liquid milk. Therefore, in this study, an efficient and accurate method based on high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF/MS) was established to determine furosine in liquid milk. A 2.00 mL milk sample was hydrolyzed with 5 mL 12.00 mol/L hydrochloric acid solution and 1 mL water at 110 ℃ for 12 h. After hydrolysis, vortex-mixing and filtration were performed. The filtrate was diluted six times with 6.00 g/L ammonium acetate solution and then analyzed. Gradient elution was performed with 0.20% formic acid aqueous solution and acetonitrile solution as mobile phases, followed by chromatographic separation on an AQ-C18 column (150 mm×3.5 mm, 5 µm). The data were collected by Q-TOF/MS with an electrospray ionization source operated in positive-ion mode. The accuracy of the quantification of furosine in milk was assessed by investigating the effects of the hydrochloric acid concentration (0.30, 1.25, and 3.00 mol/L) in the furosine solution on the MS response. The results showed that high hydrochloric acid concentrations inhibited the response signals. A good linear relationship was obtained in the mass concentration range of 0.05-2.00 mg/L, with a correlation coefficient (r) of 0.994. The limit of detection of the method was 0.50 mg/100 g, which meets the requirements of actual sample detection. The average recoveries of furosine ranged from 79.9% to 119.7% at three spiked levels of 1.52, 3.03, and 15.17 mg/100 g, with relative standard deviations of 1.4%-2.6%. The method was applied to detect 303 samples from 101 batches of pasteurized milk sold in the market, and the contents of furosine in these samples ranged from 5.1 to 11.9 mg/100 g. The proposed method is characterized with high efficiency, recovery, sensitivity, and accuracy. Thus, it can be used for the determination of large quantities of samples and provides technical support for the continuous promotion of the high-quality development of the whole dairy industry chain.

Transcriptomic response of Mytilus coruscus mantle to acute sea water acidification and shell damage.

Mytilus coruscus is an economically important marine calcifier living in the Yangtze River estuary sea area, where seasonal fluctuations in natural pH occur owing to freshwater input, resulting in a rapid reduction in seawater pH. In addition, Mytilus constantly suffers from shell fracture or injury in the natural environment, and the shell repair mechanisms in mussels have evolved to counteract shell injury. Therefore, we utilized shell-complete and shell-damaged Mytilus coruscus in this study and performed transcriptomic analysis of the mantle to investigate whether the expression of mantle-specific genes can be induced by acute seawater acidification and how the mantle responds to acute acidification during the shell repair process. We found that acute acidification induced more differentially expressed genes than shell damage in the mantle, and the biomineralization-related Gene Ontology terms and KEGG pathways were significantly enriched by these DEGs. Most DEGs were upregulated in enriched pathways, indicating the activation of biomineralization-related processes in the mussel mantle under acute acidification. The expression levels of some shell matrix proteins and antimicrobial peptides increased under acute acidification and/or shell damage, suggesting the molecular modulation of the mantle for the preparation and activation of the shell repairing and anti-infection under adverse environmental conditions. In addition, morphological and microstructural analyses were performed for the mantle edge and shell cross-section, and changes in the mantle secretory capacity and shell inner film system induced by the two stressors were observed. Our findings highlight the adaptation of M. coruscus in estuarine areas with dramatic fluctuations in pH and may prove instrumental in its ability to survive ocean acidification.

Serum sirtuin1: a potential blood biomarker for early diagnosis of Alzheimer's disease.

BACKGROUND: Sirtuin 1, a nicotinamide adenine dinucleotide-dependent deacetylase that is highly expressed in the hippocampus and anterior cortex tissues related to Alzheimer's Disease pathology, can cross the blood-brain barrier and is a promising biomarker. METHODS: A 1:1:1 case-control study was conducted and serum fasting blood glucose, triglyceride, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, SIRT1, IL-6, Aß1-42, T-tau and P-tau-181 levels were evaluated in blood samples of 26 patients form the Alzheimer's Disease group, 26 patients form the mild cognitive impairment group, and 26 individuals form the normal control group. Receiver operator characteristic curves were used to evaluate the diagnostic significance. RESULTS: Serum SIRT1 level was significantly down-regulated in the mild cognitive impairment patients and Alzheimer's Disease patients compared with that in the normal control group (P<0.05). ROC curve analysis demonstrated that SIRT1 was a promising biomarker to distinguish Alzheimer's Disease patients from the mild cognitive impairment patients and the normal control group. In addition, SIRT1 was estimated to perform well in the diagnosis of Alzheimer's Disease ([AUC] = 0.742). CONCLUSIONS: In summary, the present study suggested that serum SIRT1 might be an early promising diagnostic biomarker for Alzheimer's Disease.