CuO Nanozymes Catalyze Cysteine and Glutathione Depletion Induced Ferroptosis and Cuproptosis for Synergistic Tumor Therapy.

The latest research identifies that cysteine (Cys) is one of the key factors in tumor proliferation, metastasis, and recurrence. The direct depletion of intracellular Cys shows a profound antitumor effect. However, using nanozymes to efficiently deplete Cys for tumor therapy has not yet attracted widespread attention. Here, a (3-carboxypropyl) triphenylphosphonium bromide-derived hyaluronic acid-modified copper oxide nanorods (denoted as MitCuOHA) are designed with cysteine oxidase-like, glutathione oxidase-like and peroxidase-like activities to realize Cys depletion and further induce cellular ferroptosis and cuproptosis for synergistic tumor therapy. MitCuOHA nanozymes can efficiently catalyze the depletion of Cys and glutathione (GSH), accompanied by the generation of H2O2 and the subsequent conversion into highly active hydroxyl radicals, thereby successfully inducing ferroptosis in cancer cells. Meanwhile, copper ions released by MitCuOHA under tumor microenvironment stimulation directly bind to lipoylated proteins of the tricarboxylic acid cycle, leading to the abnormal aggregation of lipoylated proteins and subsequent loss of iron-sulfur cluster proteins, which ultimately triggers proteotoxic stress and cell cuproptosis. Both in vitro and in vivo results show the drastically enhanced anticancer efficacy of Cys oxidation catalyzed by the MitCuOHA nanozymes, demonstrating the high feasibility of such catalytic Cys depletion-induced synergistic ferroptosis and cuproptosis therapeutic concept.

Effect of telehealth interventions on adherence to endocrine therapy among patients with breast cancer: a systematic review and meta-analysis.

PURPOSE: To evaluate the effect of telehealth interventions on adherence to endocrine therapy among patients with breast cancer. METHODS: A systematic search of five English databases (PubMed, Web of Science, Embase, the American Psychological Association PsycNet, and the Cochrane Library) and four Chinese databases (Chinese National Knowledge Infrastructure, SinoMed, WanFang Data, and WeiPu Data) was performed from inception to March 31, 2023. Two investigators independently screened the available studies for eligibility and extracted relevant data. Quality assessment was conducted using the Cochrane Risk of Bias Tool. The effect size was computed based on the risk ratio for dichotomous data and standardized mean difference for continuous data using Review Manager 5.4. RESULTS: A total of 1,780 participants from eight randomized controlled trials were included. These studies involved treatment with aromatase inhibitors only (n = 3) or aromatase inhibitors plus tamoxifen (n = 5). Telehealth interventions involved web-based interventions, telephone-based interventions, interventions via mobile applications, and interventions based on technology. In three studies, subjective measures were used, while objective measures were utilized in another three. Two studies incorporated a combination of both subjective and objective measures. The duration of the interventions varied among studies, ranging from a week to 36 months. The follow-up duration ranged from 4 weeks to 36 months. The quality of included studies was moderate to high. The meta-analysis of the five studies reporting dichotomous data showed that telehealth interventions had a significant effect on adherence to endocrine therapy (RR = 0.86, 95% CI = 0.76-0.97). Moreover, four studies reported continuous data. The meta-analysis demonstrated that telehealth interventions significantly improved adherence to endocrine therapy at 1 month (SMD = 0.50, 95% CI = 0.10-0.90), 3 months (SMD = 0.58, 95% CI = 0.17-0.99), and 6 months (SMD = 0.27, 95% CI = 0.08-0.47) of follow-up. CONCLUSION: Telehealth interventions may facilitate adherence to endocrine therapy among patients with breast cancer. Further research should adopt a theory-based design and explore the longer-term effects.

Untargeted Metabolomics Using UHPLC-HRMS Reveals Metabolic Changes of Fresh-Cut Potato during Browning Process.

Surface browning plays a major role in the quality loss of fresh-cut potatoes. Untargeted metabolomics were used to understand the metabolic changes of fresh-cut potato during the browning process. Their metabolites were profiled by ultra-high performance liquid chromatography coupled with high resolution mass spectrometry (UHPLC-HRMS). Data processing and metabolite annotation were completed by Compound Discoverer 3.3 software. Statistical analysis was applied to screen the key metabolites correlating with browning process. Fifteen key metabolites responsible for the browning process were putatively identified. Moreover, after analysis of the metabolic causes of glutamic acid, linolenic acid, glutathione, adenine, 12-OPDA and AMP, we found that the browning process of fresh-cut potatoes was related to the structural dissociation of the membrane, oxidation and reduction reaction and energy shortage. This work provides a reference for further investigation into the mechanism of browning in fresh-cut products.

Developing a Noncontact Heating Matrix Spraying Apparatus with Controllable Matrix Film Formation for MALDI Mass Spectrometry Imaging.

Matrix deposition plays an important role in obtaining high-quality and reliable molecular spatial location information for matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI). To control the matrix film formation, an automatic matrix spraying apparatus was developed with the introduction of a noncontact heating lamp. Compared with the unheated condition, the noncontact heating lamp suppressed the coffee-ring effect and the diffusion phenomenon of the analyte effectively by controllable matrix film formation. Meanwhile, the signal intensity was increased by 2-5 fold. To prove the ability of the matrix deposition apparatus, the apparatus combined with metabolomics analysis was used to show the spatial distribution of the substance in sprouted potato tubers. The potential biomarkers at m/z 868.5049 and m/z 852.5101 were identified as α-solanine and α-chaconine, and the synthesis pathways were further searched. To further demonstrate the quality of MALDI images including localization and spatial resolution, lipid distribution in rat brain tissue was investigated by the developed noncontact heating matrix spraying apparatus. An excellent match with distinguishable compartments of lipids in the rat brain was obtained between the H&E-stained sections and MALDI-MSI images. These results indicate that the developed noncontact heating matrix spraying apparatus is reliable and provides a low-cost, high-quality, rapid approach for MALDI-MSI.

Effects of the appearance care on psychosocial outcomes for breast cancer: a systematic review and meta-analysis.

PURPOSE: To synthesize the evidence for the immediate and short-term effects of appearance care on psychosocial outcomes in breast cancer patients in order to inform the design of future research and clinical practice. METHODS: A search of four databases (PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science). The JBI Critical Appraisal Checklists were used by two reviewers to assess methodology quality. Subgroup analysis was conducted for the different time points measured after intervention. RESULTS: Seven studies were eligible for the meta-analysis, including two RCTs and five quasi-experimental studies, from 1994 to 2022. The type of intervention was mainly grouped education, led by beauty specialists, and the dose and frequency varied. The quality of included studies was moderate to high. The results showed that appearance care had positive immediate effect on self-esteem (SMD = 0.63, 95% CI 0.37 to 0.89), anxiety (SMD = - 0.46, 95% CI - 0.60 to - 0.31), and depression (SMD = - 0.41, 95% CI - 0.62 to - 0.19), with short-term effects on anxiety (SMD = - 0.42, 95% CI - 0.54 to - 0.34), depression (SMD = - 0.41, 95% CI - 0.55 to - 0.26), and sexual function (SMD = 0.50, 95% CI 0.18 to 0.81).The effect of appearance care on body image and quality of life was uncertain. CONCLUSION: Appearance care could be a promising intervention to improve self-esteem, anxiety, depression, and sexual function among patients with breast cancer. More high-quality RCTs are needed to validate these findings. Online appearance care programs and exploration of long-term effects should also be considered.

Barriers to family intervention to promote child and adolescent vision health: A qualitative study based on community practice in China.

PURPOSE: Child and adolescent myopia is a widespread public health problem worldwide, with high incidence, low age at onset, and severe symptoms. Family management plays a very important role in the prevention and management of myopia in children and adolescents; however, even with knowledge of the health risks of myopia, parents still continue to selectively ignore the importance of visual health, resulting in difficulties with family care related to childhood and adolescent myopia. The purpose of this study was to explore the barriers to family intervention for child and adolescent vision. METHODS: This was a qualitative phenomenological research study that used in-depth semi-structured interviews to explore the experiences of 20 parents whose children had been diagnosed with myopia in Shenzhen, China. Data were analyzed using thematic analysis methods. RESULTS: Three themes emerged: Vision health: neglected care, Going outdoors: the forgotten activity, Education: the top priority. CONCLUSIONS: Our analysis revealed that several factors contributed to barriers to promotion of visual health. One was an incorrect perception of myopia, including the effects of myopia, its non-lethality, and a view that it has minimal impact on daily life. Additionally, when parents faced a conflict between education and vision care, they tended to choose current education and ignore future development of visual problems. PRACTICE IMPLICATIONS: The findings suggest that future family intervention for child and adolescent myopia can be based on the perspective of parental health education, Simultaneously, it should also focus on the balance between education and vision care.

Effects of Organic Acids on the Release of Fruity Esters in Water: An Insight at the Molecular Level.

It is well known that organic acids (OAs) could affect the flavour of fruit juices and beverages. However, the molecular mechanism of aroma release is still unclear. In this study, the effects of citric acid (CA), L-(-)-malic acid (MA) and L-lactic acid (LA) on the release of six selected esters and their sensory perception were investigated by means of HS-GC-MS analyses and odour detection threshold determination, respectively. Meanwhile, the density functional theory (DFT) calculation was employed to explore the interaction modes between esters and OAs. HS-GC-MS analyses showed that the concentration and the type of OAs regulated the release of esters. The results were basically consistent with the detection threshold change of those esters. The DFT calculation suggested that the main intermolecular interaction was hydrogen bonds, and several esters could form a ternary ring structure with OAs through hydrogen bonds. The interactions can induce the different release behaviours of esters in OAs water solution. The number of carboxyl functional groups in OAs and the spatial conformation of esters appeared to influence the magnitude of the interaction. The above results demonstrated the mechanism of OAs affecting the release of esters and indicated a possible flavour control way by using different OAs and OA concentrations.

NIR II Light-Response Au Nanoframes: Amplification of a Pressure- and Temperature-Sensing Strategy for Portable Detection and Photothermal Therapy of Cancer Cells.

Quantitative detection of cancer cells using portable devices is promising for the development of simple, fast, and point-of-care cancer diagnostic techniques. However, how to further amplify the detection signal to improve the sensitivity and accuracy of detecting cancer cells by portable devices remains a challenge. To solve the problem, we, for the first time, synthesized folic-acid-conjugated Au nanoframes (FA-Au NFs) with amplification of pressure and temperature signals for highly sensitive and accurate detection of cancer cells by portable pressure meters and thermometers. The resulting Au NFs exhibit excellent near-infrared (NIR) photothermal performance and catalase activity, which can promote the decomposition of NH4HCO3 and H2O2 to generate corresponding gases (CO2, NH3, and O2), thereby synergistically amplifying pressure signals in a closed reaction vessel. At the same time, Au NFs with excellent peroxidase-like activity can catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) to produce TMB oxide (oxTMB) with a strong photothermal effect, thereby cooperating with Au NFs to amplify the photothermal signal. In the presence of cancer cells with overexpressing folate receptors (FRs), the molecular recognition signals between FA and FR can be converted into amplified pressure and temperature signals, which can be easily read by portable pressure meters and thermometers, respectively. The detection limits for cancer cells using pressure meters and thermometers are 6 and 5 cells/mL, respectively, which are better than other reported methods. Moreover, such Au NFs can improve tumor hypoxia by catalyzing the decomposition of H2O2 to produce O2 and perform photothermal therapy of cancer. Together, our work provides new insight into the application of Au NFs to develop a dual-signal sensing platform with amplification of pressure and temperature signals for portable and ultrasensitive detection of cancer cells as well as personalized cancer therapy.

Nitrogen-Doped Chiral CuO/CoO Nanofibers: An Enhanced Electrochemiluminescence Sensing Strategy for Detection of 3,4-Dihydroxy-Phenylalanine Enantiomers.

l-3,4-Dihydroxy-phenylalanine (l-DOPA) is the most effective drug for the treatment of Parkinson's disease, which plays a very important role in clinical and neurochemistry. However, how to achieve high-sensitivity recognition of l-DOPA still faces challenges. Here, a facile strategy is presented to construct nitrogen-doped chiral CuO/CoO nanofibers (N-CuO/CoO NFs) with nanozyme activity and electrochemiluminescence property, in which CuO/CoO NFs are used as the catalytic activity center and chiral cysteine (Cys) is used as the inducer of chiral recognition, for enantioselective catalysis and sensitive recognition of DOPA enantiomers. Notably, N doping not only enhances the enzyme-mimic activity of CuO/CoO NFs but also amplifies their electrochemiluminescence (ECL) signals in the presence of luminol. More importantly, in the presence of DOPA enantiomers, the d-cysteine (d-Cys)-modified N-CuO/CoO NFs exhibit different ECL performances; thus, d-Cys@N-CuO/CoO NFs could selectively distinguish and sensitively detect l-DOPA through ECL signals, and the detection limit is 0.29 nM for l-DOPA. In addition, it also showed good sensing performance for the determination of l-DOPA in fetal bovine serum. This is the first report on the detection of DOPA enantiomers based on an enhanced ECL strategy, providing a robust pathway for chiral discrimination and detection of chiral molecules.

Palladium Coordination Polymers Nanosheets: New Strategy for Sensitive Photothermal Detection of H2S.

New strategies for portable detection of highly toxic environmental pollutants are still in urgent need. Here, through Pd2+ and methylene blue (MB) coordination, photothermal two-dimensional palladium coordination polymers nanosheets (2D PdCPsNSs) have been synthesized for sensitive photothermal detection of H2S. The sensing mechanism is based on the decomposing effect of H2S to 2D PdCPsNSs, accompanied by the decrease of PdCPsNSs concentration and the increase of MB concentration. Upon H2S addition, the heat released from the 2D PdCPsNSs under 808 nm lasers irradiation decreased, and the heat released from the MB increased under 650 nm lasers irradiation, respectively. Such temperature change signals could be easily detected by a portable thermometer. The 2D PdCPsNSs showed highly sensitive ratiometric response to H2S with a detection limit of 30 nM. In addition, such probe presents an excellent selective ratiometric response to H2S relative to other anionic species and thiols because of the specific interaction between Pd2+ and H2S. Moreover, the probe was suitable for the ratiometric determination of H2S in different actual water samples, providing a promising platform for convenient, stable, and universal analysis of H2S.

Direct Analysis of Carbonyl Compounds by Mass Spectrometry with Double-Region Atmospheric Pressure Chemical Ionization.

Direct analysis of highly reactive volatile species such as the aliphatic aldehydes as vital biomarkers remains a great challenge due to difficulties in the sample pretreatment. To address such a challenge, we herein report the development of a novel double-region atmospheric pressure chemical ionization mass spectrometry (DRAPCI-MS) method. The DRAPCI source implements a separated structural design that uses a focus electrode to divide the discharge and ionization region to reduce sample fragmentation in the ionization process. Counterflow introduction (CFI) configuration was adopted in the DRAPCI source to reduce background noise, while ion transmission efficiency was optimized through simulating the voltage of the focus electrode and the ion trajectory of the ion source. The limits of detection (LODs) of four carbonyl compounds cyclohexanone, hexanal, heptanal, and octanal by DRAPCI-MS were between 0.1 and 3 µg·m-3, approximately two to eight times lower than those by atmospheric pressure chemical ionization mass spectrometry. Additionally, the DRAPCI-MS method carried out effective in situ analyses of the volatile components in expired milk and the exhaled breath of smokers, demonstrating the DRAPCI-MS as a practical tool to analyze complex mixtures. The DRAPCI-MS method provides a rapid, sensitive, and high-throughput technique in the real-time analysis of gaseous small-molecule compounds.

Nicotine Pharmacokinetics in Rat Brain and Blood by Simultaneous Microdialysis, Stable-Isotope Labeling, and UHPLC-HRMS: Determination of Nicotine Metabolites.

The disposition and metabolism of nicotine in the brain is an important determinant of its exposure. We have developed a novel method for the dynamic determination of nicotine and its metabolites in rat brain and blood by simultaneous microdialysis sampling, stable-isotope labeling, and ultra high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) assaying. Microdialysis probes were inserted into both the right striatum and jugular vein of Sprague-Dawley rats. The collections of dialystes after nicotine intraperitoneal injection were analyzed by the optimized UHPLC-HRMS. Nicotine-pyridyl- d4 was used as a metabolic tracer, and several stably labeled isotopes were applied to calibrate the in vivo recoveries of retrodialysis. The quadrupole-Orbitrap HRMS provided reliable characterization of the nicotine derivatives with less than 3.5 ppm mass measurement accuracy. Good precision and accuracy were obtained for different analytes within the predefined limits of acceptability and the range of the standard curve. Nicotine and its 11 metabolites were identified in most microdialysis samples from the blood and brain tissue samples. Besides cotinine as the main metabolic product of nicotine, trans-3'-hydroxy-cotinine, nicotine- N-oxide, and norcotinine were proven to be the second most abundant metabolites. The other seven nicotine products, including 4-oxo-4-(3-pyridyl)-butanoic acid, 4-hydroxy-4-(3-pyridyl)-butanoic acid, cotinine- N-oxide, nicotine- N-glucuronide, cotinine- N-glucuronide, and trans-3'- hydroxy-cotinine- O-glucuronide, which have not been determined previously in animal brain, were present in minor amounts. The pharmacokinetic profile of nicotine metabolites indicated that the metabolic characteristic of nicotine in the brain was relatively different from that in the blood. The present work would provide comprehensive evidence for clarifying the differences between nicotine metabolism in the brain and peripheral system.

Simultaneous determination of nicotine and its nine metabolites in rat blood utilizing microdialysis coupled with UPLC-tandem mass spectrometry for pharmacokinetic application.

To develop a simple and rapid method for the simultaneous determination of nicotine and its nine metabolites in rat blood, an in vivo microdialysis sampling technique coupled with ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was established for quantitation and characterization of the pharmacokinetics of nicotine and its metabolites. Microdialysis probes were inserted into the jugular vein of Sprague Dawley rats, and dialysates were collected after nicotine (0.5 mg/kg, i.p.) administration. Target analytes and corresponding deuterated internal standards were separated on a hydrophilic interaction liquid chromatography column (HILIC BEH 2.1. × 150 mm, 1.7 µm) and detected by UPLC-MS/MS under multiple reaction monitoring mode. The limits of quantification for nicotine and its nine metabolites ranged from 0.039 to 0.46 ng/mL. Intra- and inter-day precision and accuracy were well within the predefined limits of acceptability (<11 %). Pharmacokinetic results showed that the mean half-lives of nicotine, cotinine, nornicotine, norcotinine, nicotine-N'-oxide, cotinine-N'-oxide, trans-3'-hydroxy-cotinine, nicotine-N-glucuronide, cotinine-N-glucuronide, and trans-3'-hydroxy-cotinine-O-glucuronide in rat plasma were 63, 291, 175, 440, 251, 451, 322, 341, 488, and 516 min, respectively. The blood concentration-time profiles of nicotine and its nine metabolites indicate that nicotine is rapidly consumed after the administration and subsequently cotinine is generated as the main metabolite; meanwhile, cotinine and other eight minor metabolites exhibit longer retention times in rat body.

Photodynamic O2 Economizer Encapsulated with DNAzyme for Enhancing Mitochondrial Gene-Photodynamic Therapy.

Emerging research suggests that mitochondrial DNA is a potential target for cancer treatment. However, achieving precise delivery of deoxyribozymes (DNAzymes) and combining photodynamic therapy (PDT) and DNAzyme-based gene silencing together for enhancing mitochondrial gene-photodynamic synergistic therapy remains challenging. Accordingly, herein, intelligent supramolecular nanomicelles are constructed by encapsulating a DNAzyme into a photodynamic O2 economizer for mitochondrial NO gas-enhanced synergistic gene-photodynamic therapy. The designed nanomicelles demonstrate sensitive acid- and red-light sequence-activated behaviors. After entering the cancer cells and targeting the mitochondria, these micelles will disintegrate and release the DNAzyme and Mn (II) porphyrin in the tumor microenvironment. Mn (II) porphyrin acts as a DNAzyme cofactor to activate the DNAzyme for the cleavage reaction. Subsequently, the NO-carrying donor is decomposed under red light irradiation to generate NO that inhibits cellular respiration, facilitating the conversion of more O2 into singlet oxygen (1 O2 ) in the tumor cells, thereby significantly enhancing the efficacy of PDT. In vitro and in vivo experiments reveal that the proposed system can efficiently target mitochondria and exhibits considerable antitumor effects with negligible systemic toxicity. Thus, this study provides a useful conditional platform for the precise delivery of DNAzymes and a novel strategy for activatable NO gas-enhanced mitochondrial gene-photodynamic therapy.

Effects of ethyl palmitate on the release of aroma compounds in propanediol-ethanol solution and its mechanisms.

Long-chain esters (LCEs) are known to affect aroma perception, but the mechanism of their effects remains unclear. In this study, ethyl palmitate (EP), an important LCE in Osmanthus fragrans flower absolute (OFFA), was selected as a target to identify its role and mechanism. The release characteristics of 10 aroma compounds from OFFA with and without EP were obtained by headspace gas chromatography mass spectrometry (HS-GC/MS) and olfactometry evaluation, respectively. The results show that EP changes the release behaviors of volatile compounds in solution, increases their olfactory detection thresholds (ODTs), and reduces the equilibrium headspace concentrations. According to Whitman's two-film model, EP was found to change the partition coefficients and mass transfer coefficients of the compounds between the liquid and gas phases. This indicates that EP plays an important role in the scent formation of a flavor product and that it is very valuable for the style design of the flavor product.

Function Electrical Stimulation Effect on Muscle Fatigue Based on Fatigue Characteristic Curves of Dumbbell Weightlifting Training.

The parameter setting of functional electrical stimulation (FES) is important for active recovery training since it affects muscle health. Among the FES parameters, current amplitude is the most influential factor. To explore the FES effect on the maximum stimulation time, this study establishes a curve between FES current amplitude and the maximum stimulation time based on muscle fatigue. We collect 10 subjects' surface electromyography under dumbbell weightlifting training and analyze the muscle fatigue state by calculating the root mean square (RMS) of power. By analyzing signal RMS, the fatigue characteristic curves under different fatigue levels are obtained. According to the muscle response under FES, the relationship curve between the current amplitude and the maximum stimulation time is established and FES parameters' effect on the maximum stimulation time is obtained. The linear curve provides a reference for FES parameter setting, which can help to set stimulation time safely, thus preventing the muscles from entering an excessive fatigue state and becoming more active to muscle recovery training.

Non-targeted metabolomics revealed novel links between serum metabolites and primary ovarian insufficiency: a Mendelian randomization study.

Background: Primary ovarian insufficiency (POI) is a common clinical endocrine disorder with a high heterogeneity in both endocrine hormones and etiological phenotypes. However, the etiology of POI remains unclear. Herein, we unraveled the causality of genetically determined metabolites (GDMs) on POI through Mendelian randomization (MR) study with the overarching goal of disclosing underlying mechanisms. Methods: Genetic links with 486 metabolites were retrieved from GWAS data of 7824 European participants as exposures, while GWAS data concerning POI were utilized as the outcome. Via MR analysis, we selected inverse-variance weighted (IVW) method for primary analysis and several additional MR methods (MR-Egger, weighted median, and MR-PRESSO) for sensitivity analyses. MR-Egger intercept and Cochran's Q statistical analysis were conducted to assess potential heterogeneity and pleiotropy. In addition, genetic variations in the key target metabolite were scrutinized further. We conducted replication, meta-analysis, and linkage disequilibrium score regression (LDSC) to reinforce our findings. The MR Steiger test and reverse MR analysis were utilized to assess the robustness of genetic directionality. Furthermore, to deeply explore causality, we performed colocalization analysis and metabolic pathway analysis. Results: Via IVW methods, our study identified 33 metabolites that might exert a causal effect on POI development. X-11437 showed a robustly significant relationship with POI in four MR analysis methods (P IVW=0.0119; P weighted-median =0.0145; PMR-Egger =0.0499; PMR-PRESSO =0.0248). Among the identified metabolites, N-acetylalanine emerged as the most significant in the primary MR analysis using IVW method, reinforcing its pivotal status as a serum biomarker indicative of an elevated POI risk with the most notable P-value (P IVW=0.0007; PMR-PRESSO =0.0022). Multiple analyses were implemented to further demonstrate the reliability and stability of our deduction of causality. Reverse MR analysis did not provide evidence for the causal effects of POI on 33 metabolites. Colocalization analysis revealed that some causal associations between metabolites and POI might be driven by shared genetic variants. Conclusion: By incorporating genomics with metabolomics, this study sought to offer a comprehensive analysis in causal impact of serum metabolome phenotypes on risks of POI with implications for underlying mechanisms, disease screening and prevention.

Multifunctional Nanocarrier for Synergistic Treatment of Alzheimer's Disease by Inhibiting ß-Amyloid Aggregation and Scavenging Reactive Oxygen Species.

The excessive depositions of ß-amyloid (Aß) and abnormal level of reactive oxygen species (ROS) are considered as the important pathogenic factors of Alzheimer's disease (AD). Strategies targeting only one of them have no obvious effects in clinic. In this study, a multifunctional nanocarrier CICe@M-K that crosses the blood-brain barrier (BBB) efficiently was developed for inhibiting Aß aggregation and scavenging ROS synchronously. Antioxidant curcumin (Cur) and photosensitizer IR780 were loaded in mesoporous silica nanomaterials (MSNs). Their surfaces were grafted with cerium oxide nanoparticles (CeO2 NPs) and a short peptide K (CKLVFFAED). Living imaging showed that CICe@M-K was mainly distributed in the brain, liver, and kidneys, indicating CICe@M-K crossed BBB efficiently and accumulated in brain. After the irradiation of 808 nm laser, Cur was continuously released. Both of Cur and the peptide K can recognize and bind to Aß through multiple interaction including π-π stacking interaction, hydrophobic interaction, and hydrogen bond, inhibiting Aß aggregation. On the other hand, Cur and CeO2 NPs cooperate to relieve the oxidative stress in the brains by scavenging ROS. In vivo assays showed that the CICe@M-K could diminish Aß depositions, alleviate oxidative stress, and improve cognitive ability of the APP/PS1 AD mouse model, which demonstrated that CICe@M-K is a potential agent for AD treatment.

Rapid establishment of municipal sewage partial denitrification-anammox for nitrogen removal through inoculation with side-stream anammox biofilm without domestication.

Mainstream partial denitrification anammox was achieved through inoculation of side-stream mature partial nitritation anammox biofilm without domestication. The contribution of anammox to nitrogen removal was 29.4 %. Moreover, prolonging anoxic hydraulic retention time and introducing side-stream nitrite under different carbon/nitrogen ratios enriched anammox bacteria. The abundance of anammox bacteria increased by âˆ¼ 10 times ((2.19 ± 0.17) × 1012 copies gene / g dry sludge) with a total relative abundance of 18.51 %. During 258 days of operation, the contribution of anammox to nitrogen removal gradually increased to 68.8 %. The total nitrogen in the effluent decreased to 8.84 mg/L with a total nitrogen removal efficiency of 76.4 % under a carbon/nitrogen ratio of 3. This paper proposes a novel way to rapidly achieve mainstream partial denitrification anammox via inoculation with side-stream mature partial nitritation anammox biofilm. This method achieves advanced nitrogen removal from municipal wastewater, even under low carbon/nitrogen ratios.

Self-aspiration sampling design for rapid analyses of volatile organic compounds based on atmospheric pressure chemical ionization/photoionization combined ionization source mass spectrometry.

Development of combined mass spectrometry ionization sources has enabled expansion of the application and scope of mass spectrometry. A novel hybrid ionization system combining vacuum ultraviolet (VUV) and atmospheric pressure chemical ionization (APCI) was constructed. Gaseous samples were self-aspirated into an ionization zone through a capillary by negative pressure, generated by high-speed airflow based on the Venturi effect. Compared with APCI mode alone, the signal-to-noise ratio (S/N) in APCI/VUV mode was increased by about 276-times. To increase the ionization efficiency further, correlated experimental conditions were optimized. Four types of volatile organic compounds (VOCs) were tested to evaluate the performance of the APCI/VUV ion source. Excellent linearity and limit of detection were achieved for compounds in mixed solutions. Quantitative analyses of four VOCs (toluene, cyclohexanone, styrene and ethylbenzene) using APCI/VUV-MS were done, and the relative standard deviations (RSDs) were 1.57%, 6.30%, 4.49% and 8.21%, respectively, indicating that the APCI/VUV ionization source had excellent reproducibility. Our results demonstrated that the developed method was promising for analyzing VOCs as well as being rapid, simple, and easy to operate.