Harnessing Synchronous Photothermal and Photocatalytic Effects of Substoichiometric MoO3-x Nanoparticle-Decorated Membranes for Clean Water Generation.

Solar-driven interfacial evaporation provides a promising pathway for sustainable freshwater and energy generation. However, developing highly efficient photothermal and photocatalytic nanomaterials is challenging. Herein, substoichiometric molybdenum oxide (MoO3-x) nanoparticles are synthesized via step-by-step reduction treatment of l-cysteine under mild conditions for simultaneous photothermal conversion and photocatalytic reactions. The MoO3-x nanoparticles of low reduction degree are decorated on hydrophilic cotton cloth to prepare a MCML evaporator toward rapid water production, pollutant degradation, as well as electricity generation. The obtained MCML evaporator has a strong local light-to-heat effect, which can be attributed to excellent photothermal conversion via the local surface plasmon resonance effect in MoO3-x nanoparticles and the low heat loss of the evaporator. Meanwhile, the rich surface area of MoO3-x nanoparticles and the localized photothermal effect together effectively accelerate the photocatalytic degradation reaction of the antibiotic tetracycline. With the benefit of these advantages, the MCML evaporator attains a superior evaporation rate of 4.14 kg m-2 h-1, admirable conversion efficiency of 90.7%, and adequate degradation efficiency of 96.2% under 1 sun irradiation. Furthermore, after being rationally assembled with a thermoelectric module, the hybrid device can be employed to generate 1.0 W m-2 of electric power density. This work presents an effective complementary strategy for freshwater production and sewage treatment as well as electricity generation in remote and off-grid regions.

MODMS: a multi-omics database for facilitating biological studies on alfalfa (Medicago sativa L.).

Alfalfa (Medicago sativa L.) is a globally important forage crop. It also serves as a vegetable and medicinal herb because of its excellent nutritional quality and significant economic value. Multi-omics data on alfalfa continue to accumulate owing to recent advances in high-throughput techniques, and integrating this information holds great potential for expediting genetic research and facilitating advances in alfalfa agronomic traits. Therefore, we developed a comprehensive database named MODMS (multi-omics database of M. sativa) that incorporates multiple reference genomes, annotations, comparative genomics, transcriptomes, high-quality genomic variants, proteomics, and metabolomics. This report describes our continuously evolving database, which provides researchers with several convenient tools and extensive omics data resources, facilitating the expansion of alfalfa research. Further details regarding the MODMS database are available at https://modms.lzu.edu.cn/.

Single-atom engineering of hemicyanine and its amphiphilic derivative for optimized near infrared phototheranostics.

Near-infrared (NIR) dyes are widely used in the field of in vivo phototheranostics. Hemicyanine dyes (HDs) have recently received tremendous attention due to their easy synthesis and excellent NIR features. However, HDs can easily form non-fluorescent aggregates and their potential for phototherapy still needs further exploration due to their poor ability to generate reactive oxygen species (ROS). Herein, a series of hemicyanine dyes with different chalcogen atom (O, S, Se) substitutions were constructed to achieve optimized potential for phototheranostics. By replacing O with the heavy atom Se in the xanthene skeleton, CySe-NEt2 showed much more favourable features such as extended NIR absorption/emission wavelength, boosted 1O2 generation rate and higher photothermal effect. In addition, a poly(ethylene glycol) (PEG) group was introduced into the scaffold and yielded a nanotheranostic agent CySe-mPEG5K, which easily formed nanoparticles with appealing features such as excellent photostability, effective prevention of unpleasant H-aggregation, fast/selective tumor accumulation and minimum dark toxicity. Solid tumor growth was significantly suppressed through combined photodynamic therapy (PDT) and photothermal therapy (PTT) guided by NIR fluorescence (NIRF) and photoacoustic (PA) imaging. This study not only presents the first example of selenium-substituted hemicyanine dyes, but also offers a reliable design strategy for the development of potent NIR phototheranostic agents with multi-mode imaging-guided combination therapeutic ability.

Pu-erh tea and theabrownin ameliorate metabolic syndrome in mice via potential microbiota-gut-liver-brain interactions.

Metabolic syndrome (MS) is a common metabolic disorder characterized by obesity, insulin resistance, cardiovascular disease and gut microbiota dysbiosis. Pu-erh tea and its ingredient theabrownin have known functions on the reduction of body weight gain and fat accumulation. However, few studies systematicly analyze the different contributions and mechanisms of their anti-metabolic syndrome functions through multi-omics combination analysis. Here, we used metagenomics, transcriptomics and metabolomics technology to investigate the anti-metabolic syndrome mechanism of Pu-erh tea and theabrownin in MS mice. Our results suggested that Pu-erh tea and theabrownin interventions could improve the physiological functions of liver, jejunum and adipose tissues in MS mice. Hepatic transcriptome revealed that both interventions could regulate the circadian rhythm pathway. Glycerophospholipid and linoleic acid metabolism were also modulated by both interventions through serum and brain metabolome analysis. Faecal metagenome demonstrated that both interventions could increase the relative abundance of Clostridiales bacterium 42_27, Blautia coccoides and Firmicutes bacterium ASF500, but decrease the relative abundance of Brevundimonas vesicularis. Otherwise, compared with Pu-erh tea, theabrownin markedly upregulated the levels of hepatic antioxidants (i.e., SOD, GSH), prominently downregulated hepatic inflammatory factors (i.e., IL-1, IL-6, TNF-α) and malondialdehyde oxidant, but modestly reduced obesity-associated short-chain fatty acids in faeces in MS mice. Taken together, our data provided insights into the homogeneous and heterogeneous natural biological functions of theabrownin and Pu-erh tea in the treatment of metabolic syndrome.

A Noninvasive Deep Brain Stimulation Method via Temporal-Spatial Interference Magneto-Acoustic Effect: Simulation and Experimental Validation.

Deep brain transcranial stimulation is used in both research and for the treatment of neuropsychological diseases. Ideally, such stimulation should be noninvasive and precisely controlled. We propose a temporal-spatial interference magneto-acoustic stimulation (TIMAS) method combining transcranial magneto-acoustic stimulation (TMAS) and temporal interference stimulation (TIS) to achieve such stimulations, using the characteristics of the response of brain neurons to modulated low-frequency oscillation. Ultrasonic waves with two frequencies can interfere with each other to produce a modulated low-frequency signal. The modulated signal with difference frequency characteristics can be used for deep brain electrostimulation by means of magneto-acoustic coupling effect. A focused difference frequency electric field with a millimeter focal spot, a lateral resolution of 1.2 mm, an axial resolution of 6.4 mm, and a frequency of 4.13 kHz was achieved in the experimental system. These parameters are much better than previously reported magneto-acoustic coupling stimulation parameters. The measured electric field intensity for nerve stimulation was 137.2 mV/m, which meets the stimulation standard and reaches the threshold for effective nerve stimulation. Simulation and experimental results showed that TIMAS has superior penetration and temporal-spatial resolution and can generate a low-frequency envelope modulated electric field with a definite direction. TIMAS can be used as a new noninvasive low-frequency envelope modulated electrical stimulation, which can obtain high spatial resolution and high focus even at deep stimulation depths, and has low envelope frequency compared with the traditional TMAS. The method proposed in this article provides a new direction for the development of TMAS and is expected to be applied in brain science research and the treatment of major neuropsychiatric diseases related to deep brain regions.

Volatile Analysis of Wuliangye Baijiu by LiChrolut EN SPE Fractionation Coupled with Comprehensive GC×GC-TOFMS.

Wuliangye baijiu is one of the most famous Chinese liquors with a protected geographical indication. This study used LiChrolut® EN-based solid-phase extraction (SPE) and fractionation combined with comprehensive two-dimensional chromatography-time-of-flight mass spectrometry (GC×GC-TOFMS) to unveil its volatile composition. The volatiles were isolated with LiChrolut® EN-based SPE and traditional liquid-liquid extraction (LLE). The neutral/basic fractions from LLE and the SPE were fractionated on a LiChrolut® EN SPE column and analyzed by comprehensive GC×GC-TOFMS. Compared with LLE, more esters and alcohols were detected in the SPE-based extraction. The SPE fractionation and GC×GC-TOFMS analysis resulted in the identification of about 500 volatile compounds in more than 3000 peaks of the Wuliangye baijiu. The approach simplifies the complex baijiu composition into functional group-based fractions for reliable identification and analysis. This study provided a confidence volatile identification approach for Chinese baijiu based on the SPE fractionation GC×GC-TOFMS.

Folic acid oversupplementation during pregnancy disorders lipid metabolism in male offspring via regulating arginase 1-associated NOS3-AMPKα pathway.

BACKGROUND & AIMS: Folic acid supplementation is widely accepted during pregnancy, as it exerts a protective effect on neural tube defects. However, the long-term underlying effects of folic acid supplementation during pregnancy (FASDP) on offspring remain unclear. METHODS: Thirty pregnant female rats were randomly divided into normal control group, folic acid appropriate supplementation group (2.5 × FA group) and folic acid oversupplementation group (5 × FA group) and fed with corresponding folic acid concentration AIN93G diet. UPLC-Q-TOF-MS, UPLC-TQ-MS and GC-MS were performed to detect the serum metabolites profiles in adult male offspring and explore the effects of FASDP. Moreover, molecular biology technologies were used to clarify the underlying mechanism. RESULTS: We demonstrate that 2.5-folds folic acid leads to dyslipidemic-diabetic slightly in male offspring, while 5-folds folic acid aggravates the disorder and prominent hepatic lipid accumulations. Using untargeted and targeted metabolomics, total 63 differential metabolites and 12 significantly differential KEGG pathways are identified. Of note, arginine biosynthesis, arginine and proline metabolism are the two most significant pathways. Mechanistic investigations reveal that the increased levels of arginase-1 (Arg1) causes the lipid metabolism disorder by regulating nitric oxide synthase-3 (NOS3)-adenosine monophosphate activated protein kinase-α (AMPKα) pathway, resulting in lipid accumulation in hepatocytes. CONCLUSIONS: Our data suggest that maternal folic acid oversupplementation during pregnancy contributes to lipid metabolism disorder in male offspring by regulating Arg1-NOS3-AMPKα pathway.

Efficacy of Shaobei injection in the treatment of grade II-III hemorrhoids and the effect on fibulin protein expression: A study protocol of a randomized controlled trial.

BACKGROUND: Hemorrhoids are a common and seriously disruptive condition that seriously affects people's lives in terms of treatment. Injection therapy is an effective minimally invasive scheme for the treatment of grade II-III hemorrhoids, but its clinical application is limited by the adverse reactions caused by injection drugs. Some clinical studies have confirmed the efficacy and safety of Shaobei injection as a traditional Chinese medicine extract. However, there is no standard randomized controlled study to verify its efficacy and explore its potential mechanism. METHODS: This is a prospective, randomized, single blind, parallel controlled trial to study the efficacy of Shaobei injection in the treatment of grade II-III hemorrhoids and its effect on the expression of fibulin-3 and fibulin-5 in fibulin protein family. The patients will be randomly divided into a treatment group and control group. The treatment group will be treated with Shaobei injection, and the control group will be treated with rubber band ligation. The observation indexes include: visual analysis scale, postoperative hospital stay, total use of painkillers, fibulin-3 and fibulin-5, hemorrhoids recurrence, and adverse events. Finally, the data will be statistically analyzed by SPASS 18.0 software. DISCUSSION: This study will compare the efficacy of Shaobei injection with the rubber band ligation method in the treatment of grade II-III haemorrhoids and investigate its effect on the expression of fibulin-3 and fibulin-5 in the fibulin protein family. The results of this study will provide a basis for the clinical use of Paeoniflora injection as an alternative to traditional sclerosing agent in the treatment of grade II-III haemorrhoids.Trial registration: OSF Registration number:DOI 10.17605/OSF.IO/MKVDB.

The associations of circulating common and uncommon polyunsaturated fatty acids and modification effects on dietary quality with all-cause and disease-specific mortality in NHANES 2003-2004 and 2011-2012.

BACKGROUND: Associations of dietary or supplementary intake of several unsaturated fatty acids and mortality have been widely studied but the results were still hitherto inconsistent or limited. It is still need to explore the effects of these fatty acids by using the objective biomarkers. OBJECTIVE: We aimed to investigate the relevancy of several serum n-3 and n-6 fatty acids with all-cause and disease-specific mortality to confirm their health effects and effects on the associations between dietary quality and all-cause mortality. METHODS: A total of 4132 people from NHANES 2003-2004 and 2011-2012 and the mortality information was confirmed from the NDI. CPH models adjusted for known risk factors were conducted to explore the associations between circulating n-3 and n-6 fatty acids and all-cause or CVD or cancer mortality under complex sampling. We further evaluated their effects on association between dietary quality and all-cause mortality. RESULTS: A total of 437 deaths occurred during the mean follow-up of 83.34 months, including 157 CVD death and 100 cancer death. Serum LA, ALA, EPA and DHA were associated with all-cause mortality (HR in quintile5: LA:0.584, 95%CI: 0.387-0.882, Ptrend = 0.011; ALA:0.626, 95%CI: 0.432-0.907, Ptrend = 0.008; EPA:0.535, 95%CI: 0.375-0.764, Ptrend = 0.001; DHA:0.669, 95%CI: 0.468-0.955, Ptrend = 0.031). Additionally, serum EPA and ALA were respectively related to CVD and cancer mortality (Q5 HR: EPA:0.450, 95%CI: 0.23-0.854, Ptrend = 0.009; ALA:0.387, 95%CI: 0.167-0.900, Ptrend = 0.022). Serum AA, GLA, DGLA and SDA were not associated with any risk of mortality. The effect on all-cause mortality of the lower AHEI scores can be improved by adherence to a higher serum LA, EPA and DHA (in the lowest AHEI strata, LA in tertile3 compared to tertile1 HR:0.596, 95%CI: 0.366-0.970; EPA:0.660, 95%CI: 0.454-0.959; DHA:0.666, 95%CI; 0.444-1.000). CONCLUSIONS: Our results support the recent dietary recommendations to increase the intake of plant-derived and marine-derived n-6 and n-3 to improve the ability of primary and secondary prevention.

Habitual coffee intake and risk for nonalcoholic fatty liver disease: a two-sample Mendelian randomization study.

PURPOSE: Epidemiological studies support a protective role of habitual coffee and caffeine consumption against the risk of non-alcoholic fatty liver disease (NAFLD). We aimed to investigate the causal relationship between coffee intake and the risk of NAFLD. METHODS: We performed a two-sample Mendelian randomization (MR) analysis using SNPs associated with habitual coffee intake in a published genome-wide association study (GWAS) as genetic instruments and summary-level data from a published GWAS of NAFLD (1122 cases and 399,900 healthy controls) in the UK Biobank. The causal relationship was estimated with the inverse weighted method using a 4-SNP and 6-SNP instrument based on the single largest non-UK Biobank GWAS (n = 91,462) and meta-analysis (n = 121,524) of GWAS data on habitual coffee intake, respectively. To maximize power, we also used up to 77 SNPs associated with coffee intake at a liberal significance level (p ≤ 1e-4) as instruments. RESULTS: We observed a non-significant trend towards a causal protective effect of coffee intake on NAFLD based upon either the 4-SNP (OR: 0.76; 95% CI 0.51, 1.14, p = 0.19) or 6-SNP genetic instruments (OR: 0.77; 95% CI 0.48, 1.25, p = 0.29). The result also remains non-significant when using the more liberal 77-SNP instrument. CONCLUSION: Our findings do not support a causal relationship between coffee intake and NAFLD risk. However, despite the largest-to-date sample size, the power of this study may be limited by the non-specificity and moderate effect size of the genetic alleles on coffee intake.

Integration of metabolomics and proteomics to highlight altered neural development related pathways in the adult offspring after maternal folic acid supplement.

BACKGROUND & AIMS: Maternal folic acid (FA) supplement (FolS) programs the early development of an offspring. The onset of complex diseases at a later stage of life has been evidently linked with maternal FA ingestion. However, little is known regarding the underlying molecule fingerprints of the offspring. Here, we analyze the influence of maternal FolS on the metabolism of the adult offspring rats using the integrated metabolomics-proteomics. METHODS: Twenty pregnant female rats were randomly assigned to a FA supplement (FolS group) or control group which were fed AIN93G diet with 2 or 5 mg/kg FA, respectively. The blood samples from the offspring at 0, 3 and 7 weeks after birth were collected. The brain samples were obtained from the offspring at 7 weeks after birth. Serum and brain metabolite profiles were performed by UPLC-MS/MS and the brain proteomics analysis was obtained using iTRAQ-based quantitative proteomics. RESULTS: The metabolic change of the offspring for the maternal FA supplement is characterized by the phospholipids, fatty acid and amino acids, which are involved in linoleic acid, docosahexaenoic acid, glycerophosphocholine, lysophosphatidylcholine, tryptophan, glycine, arachidonic acid, γ-aminobutyric acid, and so on. Using iTRAQ-based quantitative proteomics analysis, 51 differential proteins in the brain are identified, which provides valuable insight into the underlying mechanisms of the offspring after the maternal FolS. These results demonstrate neural development related metabolites and proteins, such as docosahexaenoic acid, glycine, tryptophan, γ-aminobutyric acid, dopaminergic synapse related proteins including G protein, PPP1R1B and CAMK2G, are significantly altered, which suggests that the active neural conduction occurs in the offspring after maternal FA supplement. The behavioral testing demonstrates that the high level of memory is observed in rats with FA supplement. CONCLUSIONS: We conceive that the alterations of metabolites and protein in the offspring are associated with the maternal FA supplement and these alterations are involved in the neural development, although such animal data are limited in their ability to mimic metabolic outcomes in humans.

A chromosome-scale genome assembly of a diploid alfalfa, the progenitor of autotetraploid alfalfa.

Alfalfa (Medicago sativa L.) is one of the most important and widely cultivated forage crops. It is commonly used as a vegetable and medicinal herb because of its excellent nutritional quality and significant economic value. Based on Illumina, Nanopore and Hi-C data, we assembled a chromosome-scale assembly of Medicago sativa spp. caerulea (voucher PI464715), the direct diploid progenitor of autotetraploid alfalfa. The assembled genome comprises 793.2 Mb of genomic sequence and 47,202 annotated protein-coding genes. The contig N50 length is 3.86 Mb. This genome is almost twofold larger and contains more annotated protein-coding genes than that of its close relative, Medicago truncatula (420 Mb and 44,623 genes). The more expanded gene families compared with those in M. truncatula and the expansion of repetitive elements rather than whole-genome duplication (i.e., the two species share the ancestral Papilionoideae whole-genome duplication event) may have contributed to the large genome size of M. sativa spp. caerulea. Comparative and evolutionary analyses revealed that M. sativa spp. caerulea diverged from M. truncatula ~5.2 million years ago, and the chromosomal fissions and fusions detected between the two genomes occurred during the divergence of the two species. In addition, we identified 489 resistance (R) genes and 82 and 85 candidate genes involved in the lignin and cellulose biosynthesis pathways, respectively. The near-complete and accurate diploid alfalfa reference genome obtained herein serves as an important complement to the recently assembled autotetraploid alfalfa genome and will provide valuable genomic resources for investigating the genomic architecture of autotetraploid alfalfa as well as for improving breeding strategies in alfalfa.

Three Extraction Methods in Combination with GC×GC-TOFMS for the Detailed Investigation of Volatiles in Chinese Herbaceous Aroma-Type Baijiu.

In this study, the detailed volatile compositions of Chinese herbaceous aroma-type Baijiu (HAB) were characterized by comprehensive two-dimensional gas chromatography-time of flight mass spectrometry (GC×GC-TOFMS). A total of 606 compounds were tentatively identified by similarity, mass spectral data, and retention indices, among which 247 compounds were positively verified by authentic standards. Esters were present in higher numbers (179), followed by aldehydes and ketones (111), and alcohols (81). In addition, there were also many terpenes (82), sulfides (37), furans (29), nitrogenous compounds (29), lactones (17), and so on. Meanwhile, the extraction effects of volatile components from different sample pretreatment methods (headspace solid-phase microextraction (HS-SPME), solid phase extraction (SPE), and stir bar sorptive extraction (SBSE)) for HAB were also revealed. The results indicated that HS-SPME has a better extraction effect on easily volatile compounds, such as alcohols and sulfides, especially for terpenes. SPE was particularly beneficial for the analysis of nitrogen-containing compounds; SBSE showed medium extraction ability for most types of compounds and was more suitable for the target analysis of trace content substances.

Efficient Removal of Bisphenol A Using Nitrogen-Doped Graphene-Like Plates from Green Petroleum Coke.

Green petroleum coke, a form of industrial waste produced in the oil-refining process, was used to synthesize nitrogen-doped graphene-like plates (N-GLPs) together with melamine. In this study, characterization and batch experiments were performed to elucidate the interaction mechanism of N-GLPs and bisphenol A (BPA). Structural analysis of N-GLPs, including scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), Brunauer-Emmett-Teller (BET), and X-ray photoelectron spectroscopy (XPS), showed an obvious graphene-like structure and successful nitrogen doping. In addition, compared with 8.0 m2/g for green petroleum coke, the BET surface area of N-GLPs markedly increased to 96.6 m2/g. The influences of various factors, including contact time, temperature, and initial pH on BPA removal efficiency were investigated. It was found that 92.0% of BPA was successfully removed by N-GLPs at 50 °C. Based on the adsorption experiments, it was shown that electrostatic attraction, hydrogen bonding, and π-π interaction enhanced the adsorption capacity of N-GLPs for BPA. According to the thermodynamic data, the adsorption process was spontaneous, physical, and endothermic in nature. Therefore, N-GLPs are efficient adsorbent material to remove BPA from wastewater.

Effect of Low-Dose Vitamin K2 Supplementation on Bone Mineral Density in Middle-Aged and Elderly Chinese: A Randomized Controlled Study.

Previous studies indicated a positive effect of vitamin K2 (VK2) supplementation on bone turnover biomarkers and bone mineral density (BMD), but the doses varied, and few studies have focused on the difference between VK2 supplementation alone and in combination with calcium and vitamin D3. The aim of this study was to explore a low and effective dose of VK2 for improving BMD, and to examine whether the co-supplementation of VK2, calcium and vitamin D3 would bring greater effects. In this trial, a total of 311 community-dwelling men and postmenopausal women aged 50 and 75 years were randomly assigned to four groups, receiving placebo, 50 µg/day, 90 µg/day or co-supplementation with calcium (500 mg/day) and vitamin D3 (10 µg/day) for 1 year. At the endpoint, the bone loss of femoral neck was significantly lower in postmenopausal women in the two 90 µg groups (treatment × time, p = 0.006) compared with placebo, but no effects in men. Serum biomarkers cOC/ucOC ratio increased in the intervention groups (treatment × time, p < 0.001). VK2 supplementation in dose of 90 µg/day performed a significant effect on reducing bone loss in postmenopausal women, but in combination with calcium and vitamin D3 brought no additional effects.Trial registration This trial was registered at http://www.chictr.org.cn as chiCTR1800019240.

Comparative Transcriptomic and Physiological Analyses of Medicago sativa L. Indicates that Multiple Regulatory Networks Are Activated during Continuous ABA Treatment.

Alfalfa is the most extensively cultivated forage legume worldwide. However, the molecular mechanisms underlying alfalfa responses to exogenous abscisic acid (ABA) are still unknown. In this study, the first global transcriptome profiles of alfalfa roots under ABA treatments for 1, 3 and 12 h (three biological replicates for each time point, including the control group) were constructed using a BGISEQ-500 sequencing platform. A total of 50,742 isoforms with a mean length of 2541 bp were generated, and 4944 differentially expressed isoforms (DEIs) were identified after ABA deposition. Metabolic analyses revealed that these DEIs were involved in plant hormone signal transduction, transcriptional regulation, antioxidative defense and pathogen immunity. Notably, several well characterized hormone signaling pathways, for example, the core ABA signaling pathway, was activated, while salicylic acid, jasmonate and ethylene signaling pathways were mainly suppressed by exogenous ABA. Moreover, the physiological work showed that catalase and peroxidase activity and glutathione and proline content were increased after ABA deposition, which is in accordance with the dynamic transcript profiles of the relevant genes in antioxidative defense system. These results indicate that ABA has the potential to improve abiotic stress tolerance, but that it may negatively regulate pathogen resistance in alfalfa.

Frontal Eye Field Involvement in Color and Motion Feature-Based Attention: Single-Pulse Transcranial Magnetic Stimulation.

An object can have multiple attributes, and visual feature-based attention (FBA) is the process of focusing on a specific one of them. During visual FBA, the frontal eye field (FEF) is considered to be an important brain area related to the choice of attribute. However, the study of the FEF in FBA remains inadequate. We applied single-pulse transcranial magnetic stimulation (TMS) to the right FEF (rFEF), and designed two independent experimental FBA tasks that each involved two attributes (color and motion), to explore the action time of FEF and the spatial transmission of the FEF signal, respectively. The results of the first experiment showed that when TMS was applied to the rFEF at 100 ms after the target image stimulus began, the subjects' response time increased significantly compared with the response time in the control trials (in which TMS was applied to the vertex). This indicated that inhibiting the rFEF influenced the progress of visual FBA. The results confirm that the FEF is involved in the early stage of visual attention (at ~100 ms). In the second experiment, TMS was applied at 100 ms after the target image stimulus began. We analyzed the electroencephalogram (EEG) signal after TMS, and found that the electrode signal amplitudes for FC4 (which corresponded to the rFEF) were significantly correlated with the electrode signal amplitudes in the posterior regions. In addition, the amplitude rise of the posterior electrode signal lagged ~50 ms behind that of the FC4. Furthermore, for color and motion, different areas in the posterior brain region were involved in signal transmission. In this study, the application of single-pulse TMS was shown to provide a direct and effective method for research on the FEF, and the combination of TMS and EEG recordings allows a high degree of time resolution, which can provide powerful evidence for research on neural signal transmission.

Effects of mesalazine enemas on lymphoid follicular proctitis.

Lymphoid follicular proctitis (LFP) is an uncommon inflammatory disease that is characterized by rectal bleeding, congested and granular mucosa without ulceration and abnormal and coalescing hyperplastic lymphoid follicles without acute inflammatory changes. The lesions are usually confined to the rectal mucosa. LFP therapy is not well defined. Herein, we present a case of LFP that was resolved with a rapid administration of mesalazine enemas. A 35-year-old male was admitted to our hospital due to intermittent rectal bleeding associated with stools. Total colonoscopy revealed nodular mucosa with top pinpoint-like ulcers from the rectum to the border between the sigmoid flexure and the rectum. The nodules congested together on the lower rectal segment and occupied 2/3 of the rectal lumina. Endoscopic submucosal dissection was performed in order to obtain more specimens for histologic examination, which revealed marked lymphoid follicular hyperplasia with prominent germinal centers and a conserved mantle zone. Treatment was started with mesalazine enemas of 4 g q.d. and the patient was asymptomatic after three days. All the lesions disappeared two months later. Mesalazine enemas could be a promising and effective therapeutic option for LFP therapy.

Bubble-generating polymersomes loaded with both indocyanine green and doxorubicin for effective chemotherapy combined with photothermal therapy.

The combination of chemotherapy and photothermaltherapy (PTT) via stimuli-responsive nanovesicles has great potential in tumor treatment. In the present study, bubble-generating polymersomes, which can generate bubbles in response to low pH or hyperthermia, were fabricated to simultaneously encapsulate chemotherapeutic drug and photosensitizing agent for the synergistic chemo-photothermal tumor therapy. Photosensitizer indocyanine green (ICG) was encapsulated into the bilayer of polymersomes formed by amphiphilic triblock copolymer PCL8000-PEG8000-PCL8000 through thin film re-hydration method, while chemotherapeutic doxorubicin (DOX) was loaded into the hydrophilic lumen using a transmembrane ammonium bicarbonate gradient loading procedure. Under acidic condition or laser irradiation, the ammonium bicarbonate (NH4HCO3) encapsulated in the bubble-generating DOX-ICG-co-delivery polymersomes (BG-DIPS) would decompose to produce CO2 bubbles, resulting in destruction of vesicle structure and rapid drug release. In vitro drug release study confirmed that acidic environment and NIR laser irradiation could accelerate DOX release from the BG-DIPS. Cellular uptake study indicated that laser-induced hyperthermia highly enhanced endocytosis of BG-DIPS into 4T1-Luc cancer cells. In vitro cytotoxicity study demonstrated that BG-DIPS exhibited much higher cytotoxicity than free drugs under laser irradiation. In vivo biodistribution study indicated that BG-DIPS could accumulate in the tumor region, prolong drug retention, and increase photothermal conversion efficiency. Furthermore, in vivo antitumor study showed that BG-DIPS with laser irradiation efficiently inhibited 4T1-Luc tumor growth with reduced systemic toxicity. Hence, the formulated bubble-generating polymersomes system was a superior multifunctional nanocarrier for stimuli-response controlled drug delivery and combination chemo-photothermal tumor therapy. STATEMENT OF SIGNIFICANCE: The combination of chemotherapy and photothermaltherapy via stimuli-responsive nanovesicles has great potential in tumor treatment. Herein, bubble-generating polymersomes, which can generate bubbles in response to low pH or hyperthermia, were fabricated to simultaneously encapsulate chemotherapeutic drug (DOX) and photosensitizing agent (ICG) for the synergistic chemo-photothermal tumor therapy. The results in vitro and in vivo demonstrated that bubble-generating DOX-ICG-co-delivery polymersomes (BG-DIPS) would accelerate DOX release from the BG-DIPS and accumulate in the tumor region, prolong drug retention, and increase photothermal conversion efficiency. BG-DIPS with laser irradiation could efficiently inhibited 4T1-Luc tumor growth with reduced systemic toxicity. Hence, the formulated bubble-generating polymersomes system was a superior multifunctional nanocarrier for stimuli-response controlled drug delivery and combination chemo-photothermal tumor therapy.

Targeted metabolomics analysis reveals the association between maternal folic acid supplementation and fatty acids and amino acids profiles in rat pups.

Maternal diet during pregnancy can influence offspring's health by affecting development and metabolism. This study aimed to analyze the influence of maternal folic acid (FA) supplementation on the metabolism of rat pups using targeted metabolomics. Twenty female rats were randomly assigned to a FA supplementation (FAS group, n = 10) or control group (n = 10), which were fed AIN93G diet with 2 or 10 mg/kg FA, respectively. We then measured amino acids and their derivatives, biogenic amines, and fatty acids in the female rats and their pups by ultra-high performance liquid chromatography-triple quadrupole mass spectrometry (UHPLC/MS-MS) and gas chromatography-mass spectrometry (GC/MS-MS). In maternal rats, the significant changes of three metabolites (proline, γ-aminobutyric acid and esterified octadecatetraenoic acid, P < 0.05) were observed in FAS group. For the rat pups, FAS pups had significantly lower homocysteine and higher FA levels than control pups. The lower levels of amino acids (leucine, isoleucine, serine, proline) were obtained in FAS pups. Furthermore, there were the decreased esterified fatty acids (arachidonic acid, eicosapentaenoic acid, and docosatetraenoic acid) and free fatty acids (oleic acid, linoleic acid, γ-linolenic acid, octadecatetraenoic acid, arachidonic acid, eicosapentaenoic acid and selacholeic acid) in FAS pups. Metabolic changes in the FAS pups were characterized by changes in fatty acids and amino acids. These results suggested that FA supplementation during pregnancy influenced amino acids and fatty acids metabolism in rat pups. This study provides new insights into the regulation of amino acids and fatty acids metabolism during early life.