Central sensibility of human cases with different body mass during oral glucose tolerance test using functional magnetic resonance imaging

BACKGROUND： Because of the limitation of technique, there are few researches on regulating function o central hypothalamus by metabolism, especially the researches on real-time function. OBJECTIVE： To evaluate the response of hypothalamus to oral glucose tolerance test （OGTT） in differen body-weighted subjects by using functional magnetic resonance imaging （fMRI） so as to investigate th relationship between the sensitivity of hypothalamus in glycoregulation and disturbance of carbohydrate metabolism. DESIGN： Paired design. SETTING： Department of Radiology and Beijing Geriatrics Institute, Beijing Hospital, National Publi Health Bureau. PARTICIPANTS： A total of twenty healthy volunteers were selected from Beijing Geriatrics Institute National Public Health Bureau, including 10 subjects with obesity （5 males and 5 females; body mass 〉 28.0 kg/m2） and 10 subjects with normal body mass （5 males and 5 females; body mass from 18.5 to 23.9 kg/m2）. All subjects gave written informed consent before participating in the study. METHODS： fMRI study was performed on GE 1.5 T Signa Twinspeed Infinity with Excite. Each voluntee was ingested of glucose during the fMRI scan. T2＊ images were acquired using a single-shot gradient echo （EPI） technique. The parameters of EPI included： TR 3 000 ms, TE 40 ms, Flip angle 90°, field of view （FOV） 24 cm × 24 cm, thickness 5 mm, gap 0 mm, matrix 64 × 64, number of excitation 1. All 10 subjects with normal body mass underwent a repeat fMRI scan after consuming an equivalent amount o water without glucose on a separate day. The procedure for the fMRI scan with water intake was the same a for glucose ingestion. fMRI data were processed with Intensity Averaging Method. MAIN OUTCOME MEASURES： The central response of hypothalamus and feedback orientation during OGTT in different body-weighted subjects. RESULTS： An acute transient decrease of fMRI intensity in posterior inferior and anterior inferior o hypothalamus was observed in all subjects within 2 minutes after oral glucose intake. This decrease wa followed by a recovery to the baseline. However, obese subjects had a delayed intensity decrease [（1.96± 1.06） minutes vs. （1.04±0.71） minutes, t =2.14, P 〈 0.05] and longer recovery time [（26.62±7.35 minutes vs. （16.29±6.42） minutes, t =3.67, P 〈 0.01] as compared with normal body-weight subjects Furthermore, decreased fMRI intensity was significant different from baseline intensity [（5.7±2.5）% vs （14.3±5.5）%, t =2.56, P 〈 0.05] in obese subjects, but not in normal body-weight subjects. The area o hypothalamus in normal body-weight volunteers demonstrated no significant signal change before and afte oral water ingestion （P 〉 0.05）. CONCLUSION： Hypothalamus response to glucose loading is different in normal body-weighted and obes subjects. This suggests that fMRI is a useful tool to evaluate the central regulation of glucose metabolism.

Understanding Pseudocapacitance Mechanisms by Synchrotron X-ray Analytical Techniques

Pseudocapacitive materials that store charges via reversible surface or near-surface faradaic reactions are capable of overcoming the capacity limitations of electrical double-layer capacitors.Revealing the structure–activity relationship between the microstructural features of pseudocapacitive materials and their electrochemical performance on the atomic scale is the key to build high-performance capacitor-type devices containing ideal pseudocapacitance effect.Currently,the high brightness(flux),and spectral and coherent nature of synchrotron X-ray analytical techniques make it a powerful tool for probing the structure–property relationship of pseudocapacitive materials.Herein,we report a comprehensive and systematic review of four typical characterization techniques(synchrotron X-ray diffraction,pair distribution function[PDF]analysis,soft X-ray absorption spectroscopy,and hard X-ray absorption spectroscopy)for the study of pseudocapacitance mechanisms.In addition,we offered significant insights for understanding and identifying pseudocapacitance mechanisms(surface redox pseudocapacitance,intercalation pseudocapacitance,and the extrinsic pseudocapacitance phenomenon in battery materials)by combining in situ hard XAS and electrochemical analyses.Finally,a perspective for further depth of understanding into the pseudocapacitance mechanism using synchrotron X-ray analytical techniques is proposed.

Experimental study on angiogenesis in rabbit VX_2 brain tumor using perfusion CT

Objective： To study the perfusion CT features of rabbit VX2 brain tumor with correlation to MVD and VEGF, and to validate perfusion CT for reflection of tumor angiogenesis. Methods： Rabbit VX2 brain tumor model was established by injection of 100 μL viable tumor cells （10qmL） through a 2 mm-hole 5 mm to the right of the sagittal suture and 5 mm posterior to the coronal suture bored by dental drill. MRI was performed every 2 days after seven days of implantation to evaluate the growth of the tumor. Twenty New Zealand White rabbits with tumor size over 3 mm in diameter were randomly divided into 2 groups according to the tumor growth time with those less than 3 weeks as group 1 and those more than 3 weeks as group 2, and perfusion CT were performed accordingly. CT measurements of BV, BF and PS from tumor, peritumor and contralateral normal tissue regions were obtained. After that the animals were sacrificed and 2% Evans blue （2 mL/kg） was given intravenously in 16 of these animals 1 h prior to sacrifice to detect breakdown of the blood brain barrier. VEGF and MVD were evaluated in immunohistochemical examination of the specimens. Results： Tumor had significantly higher BV, BF and PS （P=0.000） than peritumor and normal tissue region. Tumor BV, BF and MVD in group 2 were significantly higher than that in group 1 （P〈0.01）. Significant linear correlation was found between MVD and BV （t=-0.915, P=-0.000）, MVD and BF （t=0.901, P=-0.000）, and MVD and PS （t=-0.459, P=0.042）. We also found a rank correlation between PS and blue stain of tumor （rs=0.861, P=0.000）. Conclusion： Perfusion CT can distinguish tumor from peritumor and normal tissue clearly, reflect tumor angiogenesis accurately, and provide useful information for the evaluation of brain tumor.

Boron nitride nanofibers enhanced composite PEO-based solid-state polymer electrolytes for lithium metal batteries

Polyethylene oxide(PEO)-based solid-state polymer electrolytes(SPEs)are limited by their poor cyclic stability and inferior ionic conductivity for applicating in high-safety,long-cycling and high-energy-density lithium metal batteries.Herein,porous boron nitride nanofibers(BNNFs)are filled into PEO-based SPE,which significantly suppresses Li dendrites growth and enhances the electrochemical performance of Li metal battery.BNNFs with high porosity have more active sites to connect with PEO,which can effectively reduce the crystallinity of the PEO matrix and enhance its ionic conductivity.Moreover,owing to the hardness and good stability of BNNFs,BNNFs/PEO/Li TFSI electrolyte exhibits a wider electrochemical window,better mechanical property and higher thermal stability compared with PEO/Li TFSI electrolyte.Consequently,the Li symmetric cell composed of 1%BNNFs/PEO/Li TFSI performs good cyclic stability(>1800 h),and the Li||1%BNNFs/PEO/Li TFSI||LFP full battery shows obviously improved performances in charge-discharge polarization voltage,discharge specific capacity,rate performance and cyclic stability than the Li||PEO/Li TFSI||LFP battery.

Foamed microemulsion nanodroplets loaded with chlorin e6 for epidermal-targeted treatment against psoriasis

Psoriasis is a chronic skin disease characterized by the hyperproliferation of keratinocytes and an overactive autoimmune response. Photodynamic therapy (PDT) has been established as a promising intervention for alleviating psoriasis. However, the current transdermal delivery of photosensitizers is inefficient and imprecise. In this study, we developed a foamed microemulsion nanodroplets system containing chlorin e6 (Ce6 FM), exhibiting precise epidermal targeting and retention, which targeted the aberrantly proliferating epidermal cells at psoriatic skin lesions and avoided the damage to the normal cutaneous cells. Upon application in a psoriatic mouse model, Ce6 FM efficiently induced keratinocyte apoptosis by generating reactive oxygen species under laser. Furthermore, Ce6 FM-based PDT activated the cyclooxygenase-2-induced immunosuppressive pathway in keratinocytes, resulting in the amelioration of the autoimmune microenvironment in psoriatic skin. Additionally, Ce6 FM-based PDT did not induce skin damage or atrophy associated with non-targeted halometasone treatment. Overall, Ce6 FM-based PDT holds promise as an effective, safe and compliant strategy for psoriasis treatment.

A Small-Scale Medication of Leflunomide as a Treatment of COVID-19 in an Open-Label Blank-Controlled Clinical Trial

We recently reported that inhibitors against human dihydroorotate dehydrogenase(DHODH)have broad-spectrum antiviral activities including their inhibitory efficacies on SARS-CoV-2 replication in infected cells.However,there are limited data from clinical studies to prove the application of DHODH inhibitors in Coronavirus disease 2019(COVID-19)patients.In the present study,we evaluated Leflunomide,an approved DHODH inhibitor widely used as a modest immune regulator to treat autoimmune diseases,in treating COVID-19 disease with a small-scale of patients.Cases of 10 laboratory-confirmed COVID-19 patients of moderate type with obvious opacity in the lung were included.Five of the patients were treated with Leflunomide,and another five were treated as blank controls without a placebo.All the patients accepted standard supportive treatment for COVID-19.The patients given Leflunomide had a shorter viral shedding time(median of5 days)than the controls(median of 11 days,P=0.046).The patients given Leflunomide also showed a significant reduction in C-reactive protein levels,indicating that immunopathological inflammation was well controlled.No obvious adverse effects were observed in Leflunomide-treated patients,and they all discharged from the hospital faster than controls.This preliminary study on a small-scale compassionate use of Leflunomide provides clues for further understanding of Leflunomide as a potential antiviral drug against COVID-19.

Prevalence and factors associated with pentavalent vaccination:a cross-sectional study in Southern China

Background Immunization is one of the most far-reaching and cost-effective strategies for promoting good health and saving lives.A complex immunization schedule,however,may be burdensome to parents and lead to reduced vaccine compliance and completion.Thus,it is critical to develop combination vaccines to reduce the number of injections and simplify the immunization schedule.This study aimed to investigate the current status of the pentavalent diphtheria-tetanus-acellular pertussis inactivated poliomyelitis andHaemophilus influenzae type B conjugate(DTaP-IPV/Hib)vaccination in Southern China as well as explore the factors in the general population associated with uptake and the differences between urban and rural populations.Methods A cross-sectional study was conducted with recently enrolled kindergarten students in Hainan Province between December 2022 and January 2023.The study employed a stratified multistage cluster random sampling method.Information regarding the demographic characteristics and factors that influence decisions were collected from the caregivers of children via an online questionnaire.Multivariate logistic regression was used to determine the factors associated with the status of DTap-IPV/Hib vaccinations.Results Of the 4818 valid responses,95.3%of children were aged 3-4 years,and 2856(59.3%)held ruralhukou.Coverage rates of the DTaP-IPV/Hib vaccine,from 1 to 4 doses,were 24.4%,20.7%,18.5%,and 16.0%,respectively.Caregivers who are concerned about vaccine efficacy[adjusted odds ratio(aOR)=1.53,95%confidence interval(CI):1.30-1.79],the manufacturer(aOR=2.05,95%CI:1.69-2.49),and a simple immunization schedule(aOR=1.26,95%CI:1.04-1.54)are factors associated with a higher likelihood of vaccinating children against DTaP-IPV/Hib.In addition,caregivers in urban areas showed more concern about the vaccine price(P=0.010)and immunization schedule(P=0.022)in regard to vaccinating children.Conclusions The DTaP-IPV/Hib vaccine coverage rate in Hainan Province remains low.Factors such as lower socioeconomic status,cultural beliefs,concerns about vaccine safety,and cost may hinder caregivers from vaccinating their children.Further measures,such as health education campaigns to raise knowledge and awareness,and encouragement of domestic vaccine innovation,which would reduce out-of-pocket costs,could be implemented to improve the coverage of DTap-IPV/Hib vaccination.

Comparative metabolomics provides novel insights into the basis of petiole color differences in celery(Apium graveolens L.)

Plant metabolites are important for plant development and human health.Plants of celery(Apium graveolens L.)with different-colored petioles have been formed in the course of long-term evolution.However,the composition,content distribution,and mechanisms of accumulation of metabolites in different-colored petioles remain elusive.Using ultra-high performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS),1159 metabolites,including 100 lipids,72 organic acids and derivatives,83 phenylpropanoids and polyketides,and several alkaloids and terpenoids,were quantified in four celery cultivars,each with a different petiole color.There were significant differences in the types and contents of metabolites in celery with different-colored petioles,with the most striking difference between green celery and purple celery,followed by white celery and green celery.Annotated analysis of metabolic pathways showed that the metabolites of the different-colored petioles were significantly enriched in biosynthetic pathways such as anthocyanin,flavonoid,and chlorophyll pathways,suggesting that these metabolic pathways may play a key role in determining petiole color in celery.The content of chlorophyll in green celery was significantly higher than that in other celery cultivars,yellow celery was rich in carotenoids,and the content of anthocyanin in purple celery was significantly higher than that in the other celery cultivars.The color of the celery petioles was significantly correlated with the content of related metabolites.Among the four celery cultivars,the metabolites of the anthocyanin biosynthesis pathway were enriched in purple celery.The results of quantitative real-time polymerase chain reaction(q RT-PCR)suggested that the differential expression of the chalcone synthase(CHS)gene in the anthocyanin biosynthesis pathway might affect the biosynthesis of anthocyanin in celery.In addition,HPLC analysis revealed that cyanidin is the main pigment in purple celery.This study explored the differences in the types and contents of metabolites in celery cultivars with different-colored petioles and identified key substances for color formation.The results provide a theoretical basis and technical support for genetic improvement of celery petiole color.

Novel functional food from an invasive species Polygonum cuspidatum:safety evaluation,chemical composition,and hepatoprotective effects

Accidentally,we found that the shoots of Polygonum cuspidatum(SPC)have been consumed for centuries as a traditional vegetable in the Shennongjia region of China.Local residents believe that SPC has biological effects such as antibacterial,anti-aging,and antioxidant.To provide scientific support for the use of SPC as a functional food,SPC was evaluated in terms of safety,chemical composition,and antioxidant activity both in vivo and in vitro.In the first,SPC exhibited no adverse cytotoxic effects or acute toxicity in mice.Then the chemical composition of SPC was determined by ultrahigh performance liquid chromatography–electrospray ionization–quadrupole time of flight tandem mass spectrometry(UHPLC-ESI-QTOF-MS/MS).Twenty-two compounds were identified from the SPC extracts,including phenolic,flavonoid,stilbene,and anthra-quinone.Finally,an acute ethanol-induced oxidative stress model in mice showed hepatoprotective effects.In brief,our study indicated that SPC is a safe,multifunctional food with antioxidant and hepatoprotective activities.Importantly,the consumption of SPC as a functional food provides a novel strategy for the efficient utilization of the invasive plant.

An antigen self-assembled and dendritic cell-targeted nanovaccine for enhanced immunity against cancer

The rise of nanotechnology has opened new horizons for cancer immunotherapy.However,most nano vaccines fabricated with nanomaterials suffer from carrier-related concerns,including low drug loading capacity,unpredictable metabolism,and potential systemic toxicity,which bring obstacles for their clinical translation.Herein,we developed an antigen self-assembled nanovaccine,which was resulted from a simple acryloyl modification of the antigen to induce self-assembly.Furthermore,a dendritic cell targeting head mannose monomer and a mevalonate pathway inhibitor zoledronic acid(Zol)were integrated or absorbed onto the nanoparticles(denoted as MEAO-Z)to intensify the immune response.The synthesized nano vaccine with a diameter of around 70 nm showed successful lymph node transportation,high dendritic cell internalization,promoted costimulatory molecule expression,and preferable antigen cross-presentation.In virtue of the above superiorities,MEAO-Z induced remarkably higher titers of serum antibody,stronger cytotoxic T lymphocyte immune responses and IFN-γsecretion than free antigen and adjuvants.In vivo,MEAO-Z significantly suppressed EG7-OVA tumor groth and prolonged the survival time of tumor-bearing mice.These results indicated the translation promise of our self-assembled nano vaccine for immune potentiation and cancer immunotherapy.

Negatively charged insulated boron nitride nanofibers directing subsurface zinc deposition for dendrite-free zinc anodes

The practical application of aqueous zinc-ion batteries(ZIBs)is limited by the growth of dendrite during cycling.How to rationally design and construct an efficient artificial interface layer by selecting suitable building units to control the dendrite growth is still a challenge.Herein,a porous boron nitride nanofibers(BNNFs)artificial interface layer was constructed,and its working mechanisms were revealed by both experiments(electrochemical characterization and in-situ optical microscope)and theoretical calculations(density functional theory(DFT)and finite element simulation).The insulated BNNFs layer leads to position-selected electroplating between BNNFs layer and Zn foil.The unique negatively charged surface and porosity of BNNFs contribute to the self-concentrating and pumping features of Zn ions,thus suppressing the concentration polarization on the Zn surface.Additionally,densely arranged porous BNNFs have a shunt effect on Zn ions diffusion,resulting in uniform distributions of Zn ions and electric field.The introduced BNNFs layer not only makes Zn deposition uniform but also restrains the dendrite growth,therefore the Zn+BNNFs symmetric cells perform ultralong stable cycling for 1,600 h at 1 mA·cm–2 and more than 500 h at 10 mA·cm–2.Moreover,Zn+BNNFs||CNT/MnO2 battery presents a high initial capacity of 293.6 mAh·g–1 and an excellent retention rate of 97.6%at 1 A·g–1 after 400 cycles,while Zn||CNT/MnO2 battery only maintains 37.1%discharge capacity.This artificial interface layer with negatively charged BNNFs exhibits excellent dendrite-inhibit and may have enormous prospects in other metal batteries.

AN IMPROVED RANDOM WALK SEGMENTATION ON THE LUNG NODULES

In this paper, we proposed a semi-automatic technique with a marker indicating the target to locate and segment nodules. For the lung nodule detection, we develop a Gabor texture feature by FCM （Fuzzy C Means） segmentation. Given a marker indicating a rough location of the nodules, a decision process is followed by applying an ellipse fitting algorithm. From the ellipse mask, the foreground and background seeds for the random walk segmentation can be automatically obtained. Finally, the edge of the nodules is obtained by the random walk algorithm. The feasibility and effectiveness of the proposed method are evaluated with the various types of the nodules to identify the edges, so that it can be used to locate the nodule edge and its growth rate.

Zoledronate-loaded aluminum salt nanovaccines amplify cellular immune response by enhancing cross-presentation

Being a Th2 stimulator,classic aluminum salt-based adjuvants only stimulate weak cellular immune responses that are required for vaccination against intracellular viruses or cancerous cells.As a thirdgeneration bisphosphonate,zoledronate(ZOL)can enhance antigen crosspresentation by inhibiting key enzymes of the mevalonate pathway.Here,we developed the subunit antigen ovalbumin(OVA)and ZOL co-loaded aluminum hydroxide nanoparticles(APN-OVA-ZOL)and investigated their capacity for inducing cellular immune responses against the antigen.Our results showed that the developed nanovaccines could successfully encapsulate OVA and ZOL,and enabled efficient lymph node delivery.Benefited by the mevalonate pathway inhibition effect of ZOL,APN-OVA-ZOL significantly promoted crosspresentation.As a result,APN-OVA-ZOL induced robust cellular immunity,including the activation of T and B cells.In a EG7-OVA tumor-bearing murine model,APN-OVA-ZOL significantly inhibited the tumor growth and prolonged mice survival.This work provided a strong empirical foundation indicating that zoledronate-loaded aluminum salt nanovaccines had a strong potency for cancer immunotherapy.