Plant-based meat analogues aggravated lipid accumulation by regulating lipid metabolism homeostasis in mice

To determine the effects of plant-based meat analogues on the metabolic health and the possible mechanisms,mice were fed with a real pork diet(AP),a real beef diet(AB),a plant-based pork analogue diet(PP)and plant-based beef analogue diet(PB)for 68 days.Compared with real meat,the plant-based meat analogues increased food and energy intake,body weight,white fat and liver weight and caused adipocyte hypertrophy,hepatic lipid droplet accumulation,and inflammatory responses in mice.Metabolomics revealed that plantbased meat analogues altered the composition of serum metabolites,which regulated lipid metabolism homeostasis.The PB diet upregulated gene expression related to lipid synthesis,lipolysis and adipocyte differentiation while the PP diet upregulated expression of lipolysis-related genes but downregulated expression of adipocyte differentiation-related genes in white adipose tissue.Meanwhile,both PP and PB diets upregulated lipid influx-and synthesis-related genes but downregulated lipid oxidation-related genes in liver.The specific metabolite biomarkers may affect fat accumulation mainly by direct lipid metabolism pathways or indirect amino acid metabolism,protein digestion and absorption,bile secretion,aminoacyl-tRNA biosynthesis,neuroactive ligand-receptor interaction and ABC transporters pathways.These findings provide a new insight into understanding the differences in nutritional functions of meat and plant-based meat analogues.

Effect of dietary with Zhibai dihuang pills and gonadotropinreleasing-hormone-analogue on girls with precocious and rapidly progressive puberty

BACKGROUND At present,the clinical mechanisms underlying precocious puberty remain unclear,making effective intervention for children experiencing this condition and rapidly progressive puberty essential.AIM To explore the effects of Zhibai dihuang pills and gonadotropin-releasing hormone analogue(GnRHa)on growth and ovarian function in girls with precocious puberty.METHODS The clinical data of 84 adolescent girls with precocious puberty and rapidly progressive puberty from February 2017 to August 2023 were retrospectively analyzed.Girls were divided into a control group and an observation group,with 42 cases in each group.The control group received diet intervention combined with GnRHa treatment,while the observation group received diet intervention combined with Zhibai dihuang pills+GnRHa treatment.Outcomes such as clinical efficacy,growth indicators,ovarian function,and adverse reactions were compared between the two groups.RESULTS The observation group showed superior clinical efficacy compared to the control group(P<0.05).Prior to the intervention,no significant differences were found in growth or ovarian function between the groups(P>0.05).Post-intervention,the observation group exhibited significantly lower rates in growth,height,and bone age,along with reduced levels of progesterone,testosterone,estradiol,prolactin,luteinizing hormone,and follicle-stimulating hormone compared to the control group(P<0.05).The incidence of adverse reactions was similar across both groups(P>0.05).CONCLUSION Combining Zhibai dihuang pills with GnRHa and dietary intervention effectively improves growth,enhances ovarian function,and minimizes adverse reactions in adolescent girls with precocious and rapidly progressive puberty.

Synthesis of novel biodegradable poly(ethylene glycol) analogue:Water-soluble aliphatic polyester with pendant oligo(ethylene glycol) chains

A novel poly（ethylene glycol） （PEG） analogue composed of aliphatic polyester backbone and pendant oligo（ethylene glycol） short chains is reported. The PEG analogue is a copolymer synthesized by ring-opening alternating copolymerization of succinic anhydride with 2-（（2-（2-metho xyethoxy）ethoxy）methyl）oxirane. The structure of the copolymer was confirmed by ^1H NMR spectrum. The effects of the monomer feed ratio on the copolymerization were studied and the polymerization mechanism was given. The PEG analogue disclosed is water-soluble and expected to have promising applications in biomedical fields as a substitute of PEG due to the existence of degradable ester bond in the backbone.

An Approach to New Water-soluble Oligo(ethylene glycol) Camptothecin Analogues by 1,3-Dipolar Cycloaddition

Combined with an effective copper-catalyzed triazole-forming reaction, a series of novel camptothecin derivatives were synthesized. Incorporating oligo（ethylene glycol） chains into the derivatives enhanced their water-solubility when compared to the parent compound （up to 55-fold）.

Moderate heat treatment of CoFe Prussian blue analogues for enhanced oxygen evolution reaction performance

Prussian blue analogues(PBAs) with inherent ordered structures and abundant metal ion sites are widely explored as precursors for various electrochemical applications,including oxygen evolution reaction(OER).Using a range of characterization techniques including Fourier-transform infrared spectroscopy(FT-IR),X-ray photoelectron spectroscopy(XPS),X-ray diffraction(XRD) and energy dispersive spectroscopy(EDS),this work discloses the process of replacement of K^(+)by NH4^(+)in the interstitial spaces of the CoFe PBA by a hot aqueous urea solution,which influences the transformation of PBAs under further heat treatment and the OER performance of the deriva tives.After heat treatment at 400℃ under Ar flow,high-resolution transmission electron microscopy(HRTEM) images reveal that CoFe alloy nanoparticles grew on the crystalline cubes of CoFe PBA with K^(+),while CoFe PBA cubes with NH4^(+)become amorphous.Besides,the derivative of CoFe PBA with NH4^(+)(Ar-U-CoFe PBA) performs better than the derivative of CoFe PBA with K^(+)(Ar-CoFe PBA) in OER,registering a lower overpotential of 305 mV at 10 mA cm^(-2),a smaller Tafel slope of 36.1 mV dec^(-1),and better stability over a testing course of 20 h in 1.0 M KOH.A single-cell alkaline electrolyzer,using Ar-U-CoFe PBA and Pt/C for the anodic and cathodic catalyst,respectively,requires an initial cell voltage of 1.66 V to achieve 100 mA cm^(-2)at 80℃,with negligible degradation after100 h.

Ultralow-Energy-Barrier H_(2)O_(2)Dissociation on Coordinatively Unsaturated Metal Centers in Binary Ce-Fe Prussian Blue Analogue for Efficient and Stable Photo-Fenton Catalysis

The low intrinsic activity of Fenton catalytic site and high demand for light-energy input inhibit the organic-pollution control efficiency of photo-Fenton process.Here,through structural design with density functional theory(DFT)calculations,Ce is predicted to enable the construction of coordinatively unsaturated metal centers(CUCs)in Prussian blue analogue(PBA),which can strongly adsorb H_(2)O_(2)and donate sufficient electrons for directly splitting the O-O bond to produceOH.Using a substitution-co-assembly strategy,binary Ce-Fe PBA is then prepared,which rapidly degrades sulfamethoxazole with the pseudo-first-order kinetic rate constant exceeding reported values by 1-2 orders of magnitude.Meanwhile,the photogenerated electrons reduce Fe(Ⅲ)and Ce(Ⅳ)to promote the metal valence cycle in CUCs and make sulfamethoxazole degradation efficiency only lose 6.04%in 5 runs.Overall,by introducing rare earth metals into transition metal-organic frameworks,this work guides the whole process for highly active CUCs from design and construction to mechanism exploration with DFT calculations,enabling ultrafast and stable photo-Fenton catalysis.

Recharge processes limit the resource elements of Qarhan Salt Lake in western China and analogues in the evaporite basins

The Qarhan Salt Lake(QSL)in western China is K-Sr-Li-B-Br-Rb multi-resource coexisting Quaternary brine deposits.Significant research efforts have been directed to the origin of K-Li resources and evolutionary history of the QSL.However,the study on the different sources,recharge processes,and differential distribution patterns for these resource elements in brine deposits is still inadequate.Therefore,we measured Li-B concentrations and H-O-Sr-B isotopic compositions of different waters(river,spring,and brine)from the QSL,combined with the reported K-Sr contents and multiple isotopes of waters,to discuss the recharge,source of K-Sr-Li-B and their spatial distributions,by analogy with other evaporite basins in the world.The results show that:(1)the K-Li-B-Sr elemental concentrations of brines and their spatial distribution in the QSL are diverse;(2)high K and Sr values are distributed in Dabuxun and Qarhan sections,respectively,which are controlled by Ca-Cl springs in the northern QSL;on the contrary,Li and B values are enriched in the Bieletan section and are charged by thermal springs in the Kunlun Mountains;(3)the formation and evolution of Ca-Cl and thermal springs constrain fundamentally on the recharge processes of K-Sr and Li-B elements in the terminal salt lakes of the Qaidam Basin(QB);(4)some analogues of recharge processes limit the resource elements of the QSL and other salt lakes(Da Qaidam,Lop Nur,Zhabuye,Atacama,and Guayatayoc)in the world provides a reference for the resource exploration in deep formation waters in the evaporite basins.

Viral infection parameters not nucleoside analogue itself correlates with host immunity in nucleoside analogue therapy for chronic hepatitis B

AIM:To determine the relationship between host immunity and the characteristics of viral infection or nucleoside analogues(NAs)themselves in patients with chronic hepatitis B(CHB)receiving NA therapy.METHODS:Fifty-two hepatitis B envelope antigen(HBeAg)positive CHB patients were enrolled and divided equally into two groups.One group received telbivudine(LDT,600 mg/d),and the other group received lamivudine(LAM,100 mg/d).Clinical,virological and immunological parameters were assessed at the baseline and at 4,12,24,36 and 48 wk.RESULTS:Both groups achieved significant hepatitis B virus(HBV)replication inhibition and alanine aminotransferase normalization at 48 wk.At the baseline,compared to healthy controls,CHB patients had a lower circulating CD8 T cell frequency(29.44%±11.55%vs 37.17%±7.30%,p=0.03)and higher frequencies of programmed death 1 positive CD8 T cells(pD-1+CD8 T)(16.48%±10.82%vs 7.02%±3.62%,p=0.0001)and CD4+CD25+Foxp3+T regulatory cells(Tregs)(23.64%±9.38%vs 13.60%±6.06%,p=0.001).On therapy,at the beginning 24 wk with the levels of hepatitis B virus deoxyribonucleic acid(HBV DNA)and HBeAg declining,the frequencies of pD-1+CD8 T cells and Treg cells gradually and significantly declined at 12 and 24 wk in both therapy groups.At treatment week 4,patients treated with LDT had a lower frequency of pD-1+CD8 T cells compared to patients treated with LAM(10.08%±6.83%vs 20.51%±20.96%,p=0.02).The frequency of pD-1+CD8 T cells in all of the CHB patients was significantly correlated with both the HBV DNA level(r=0.45,p=0.01)and HBeAg level(r=0.47,p=0.01)at treatment week 24,but the frequency of Treg cells was only significantly correlated with the HBeAg level(r=0.44,p=0.02).Furthermore,the ability of CD8 T cells to secrete pro-inflammatory cytokines was partially restored after 24 wk of therapy.CONCLUSION:NA-mediated HBV suppression could down-regulate the production of negative regulators of host immunity during the first 24 wk of therapy and could partially restore the ability of CD8 T cells to secrete pro-inflammatory cytokines.This immune modulating response may be correlated with the levels of both HBV DNA and HBeAg.

Structure and kinematic analysis of the deepwater area of the Qiongdongnan Basin through a seismic interpretation and analogue modeling experiments

Located at the northwest continental slope of the South China Sea, the Qiongdongnan Basin bears valley-shaped bathymetry deepening toward east. It is separated from the Yinggehai Basin through NW-trending Indo-China-Red River shear zone, and connected with NW subsea basin through the Xisha Trough. Along with the rapid progress of the deepwater exploration, large amounts of high resolution geophysical and geological data were accumulated. Scientific researches about deepwater basins kept revealing brand new tectonic and sedimentary discoveries. In order to summarize the structural features and main controlling factors of the deepwater Qiongdongnan Basin, a series of researches on basin architecture, fault activities, tectonic deformation and evolution were carried out. In reference to analogue modeling experiments, a tectonic situation and a basin formation mechanism were discussed. The researches indicate that：the northern boundary of the Qiongdongnan Basin is strongly controlled by No. 2 fault. The overlapping control of two stress fields from the east and the west made the central depression zone extremely thinned. Combined with the changed stress field, the segmentation of a preexisting weakness zone made the sags in the east experiencing different rifting histories from the west ones. The NE-trending west segment of the Qiongdongnan Basin experienced strong rifting during Eocene, while the roughly EW-trending sags in the east segment show strong rifting during late Eocene and early Oligocene. Local structures such as NW-trending basal fault and inherited uplifts controlled the lateral segmentation. So first order factors such as regional stress field and preexisting weakness zone controlled the basin zonation, while the second order factors determined the segmentation from east to west.

Analogue correction method of errors and its application to numerical weather prediction

In this paper, an analogue correction method of errors （ACE） based on a complicated atmospheric model is further developed and applied to numerical weather prediction （NWP）. The analysis shows that the ACE can effectively reduce model errors by combining the statistical analogue method with the dynamical model together in order that the information of plenty of historical data is utilized in the current complicated NWP model, Furthermore, in the ACE, the differences of the similarities between different historical analogues and the current initial state are considered as the weights for estimating model errors. The results of daily, decad and monthly prediction experiments on a complicated T63 atmospheric model show that the performance of the ACE by correcting model errors based on the estimation of the errors of 4 historical analogue predictions is not only better than that of the scheme of only introducing the correction of the errors of every single analogue prediction, but is also better than that of the T63 model.

3D-QSAR Study of Melittin and Amoebapore Analogues by CoMFA and CoMSIA Methods

Peptides are one of the indispensable substances in life. The use of computer aided drug design(CADD) methods to design peptides and peptiodmimetics can short the design cycle, save research funding, improve the level of whole research to a large extent and guide the discovery of new drugs. In this paper, Melittin and amoebapore three-dimensional quantitative structureactivity relationship(3D-QSAR) models were established by using comparative molecular field analysis(CoMFA) and comparative molecular similarity indices analysis(CoMSIA) method. The result shows that, the correlation coefficient(q^2) was 0.583 and non-cross-validation correlation coefficient(r^2) was 0.972 for the melittin CoMFA model. The q^2 and r^2 were 0.630 and 0.995 for the best CoMSIA model, 0.645 and 0.993 for the amoebapore CoMFA model, and 0.738 and 0.996 for the best CoMSIA model. The statistical parameters demonstrated that the CoMFA and CoMSIA models had both good predictive ability and high statistical stability, and can provide theoretical basis for designing new high activity polypeptide drugs.

Application of nucleoside analogues to liver transplant recipients with hepatitis B

Hepatitis B is a common yet serious infectious disease of the liver, affecting millions of people worldwide. Liver transplantation is the only possible treatment for those who advance to end-stage liver disease. Donors positive for hepatitis B virus(HBV) core antibody(HBc Ab) have previously been considered unsuitable for transplants. However, those who test negative for the more serious hepatitis B surface antigen can now be used as liver donors, thereby reducing organ shortages. Remarkable improvements have been made in the treatment against HBV, most notably with the development of nucleoside analogues(NAs), which markedly lessen cirrhosis and reduce post-transplantation HBV recurrence. However, HBV recurrence still occurs in many patients following liver transplantation due to the development of drug resistance and poor compliance with therapy. Optimized prophylactic treatment with appropriate NA usage is crucial prior to liver transplantation, and undetectable HBV DNA at the time of transplantation should be achieved. NA-based and hepatitis B immune globulin-based treatment regimens can differ between patients depending on the patients' condition, virus status, and presence of drug resistance. This review focuses on the current progress in applying NAs during the perioperative period of liver transplantation and the prophylactic strategies using NAs to prevent de novo HBV infection in recipients of HBc Ab-positive liver grafts.

Risk for hepatocellular carcinoma in the course of chronic hepatitis B virus infection and the protective effect of therapy with nucleos(t)ide analogues

Hepatocellular carcinoma(HCC) is a major health problem worldwide, representing one of the leading causes of death. Chronic hepatitis B virus(HBV) infection(CHB) is the most important etiologic factor of this tumor, accounting for the development of more than50% of the cases in the world. Primary prevention ofHCC is possible by hepatitis B vaccination conferring protection from HBV infection. However, according to the World Health Organization Hepatitis B Fact sheet N° 204(update of July 2014) globally there exists a large pool of > 240 million people chronically infected with HBV who are at risk for development of HCC. These individuals represent a target population for secondary prevention both of cirrhosis and of HCC. Since ongoing HBV replication in CHB is linked with the progression of the underlying liver disease to cirrhosis as well as with the development of HCC, effective antiviral treatment in CHB has also been evaluated in terms of secondary prevention of HCC. Currently, most patients with active CHB are subjected to long term treatment with the first line nucleos(t)ide analogues entecavir and tenofovir. These compounds are of high antiviral potency and have a high barrier to HBV resistance compared to lamivudine, adefovir dipivoxil and even telbivudine. Many studies have shown that patients under antiviral treatment, especially those in virological remission, develop less frequently HCC compared to the untreated ones. However, the risk for development of HCC cannot be eliminated. Therefore, surveillance for the development of HCC of patients with chronic hepatitis B must be lifelong or until a time in the future when new treatments will be able to completely eradicate HBV from the liver particularly in the early stages of CHB infection. In this context, the aim of this review is to outline the magnitude of the risk for development of HCC among patients with CHB, in the various phases of the infection and in relation to virus, host and environmental factors as evaluated in the world literature. Moreover, the benefits of antiviral treatment of CHB with nucleos/tide analogs, which have changed the natural history of the disease and have reduced but not eliminated the risk of HCC are also reviewed.

Migration of Some Elements and Radionuclides across aGranite-Granite Contact Zone: A Natural Analoguefor Safe Disposal of High-Level Radwastes

Abstract Elements and natural radionuclides in the contact zone of two granites with different ages would migrate from one to the other because of the difference in their chemical contents and later water-rock interactions. This migration could serve as an analogue for the near-field process of radwastes in a high-level radwaste deep geological disposal repository.

Nanocrystals for enhancement of oral bioavailability of poorly water-soluble drugs

Nanocrystals,a carrier-free colloidal delivery system in nano-sized range,is an interesting approach for poorly soluble drugs.Nanocrystals provide special features including enhancement of saturation solubility,dissolution velocity and adhesiveness to surface/cell membranes.Several strategies are applied for nanocrystals production including precipitation,milling,high pressure homogenization and combination methods such as Nano-Edge^(TM),SmartCrystal and Precipitation-lyophilization-homogenization(PLH)technology.For oral administration,many publications reported useful advantages of nanocrystals to improve in vivo performances i.e.pharmacokinetics,pharmacodynamics,safety and targeted delivery which were discussed in this review.Additionally,transformation of nanocrystals to final formulations and future trends of nanocrystals were also described.

Synthesis and cytotoxic activity of novel curcumin analogues

Five novel curcumin analogues bearing different substituents at 4-position of phenyl group were synthesized. Their structures were confirmed by NMR and HRMS spectrum. Their cytotoxic activities against six tumor cell lines were tested by the standard MTT assay in vitro. The results indicated that four analogues （1A-1C, 1E） with solubilizing moieties showed selective potent cytotoxicity against HepG2, HeLa and CT26 cell lines, and analogue 1A and 1C exhibited more potent cytotoxicity than curcumin against CT26 cell line. It was suggested that introduction of appropriate substituents to 4-position of phenyl group might be a potential option for structural modification of curcumin.

Using a modern analogue to interpret depositional position in ancient fluvial-tidal channels:Example from the McMurray Formation,Canada

The fluvial-tidal transition(FTT)is a complex depositional zone,where fluvial flow is modified by tides as rivers approach a receiving marine basin.Variations in the relative importance of tidal versus fluvial processes lead to a distinctive distribution of sediments that accumulate on channel bars.The FTT generally consists of three broad zones:(1)a freshwater-tidal zone;(2)a tidally influenced freshwater to brackish-water transition:and(3)a zone of relatively sustained brackish-water conditions with stronger tides.A very common type of deposit through the fluvial-tidal transition,especially on the margins of migrating channels,is inclined heterolithic stratification(IHS).At present,a detailed account of changes in the character of IHS across the FIT of a paleo-channel system has not been reported,although a number of modern examples have been documented.To fill this gap,we quantitatively assess the sedimentology and ichnology of IHS from seven cored intervals in three geographic areas situated within the youngest paleovalley("A"Valley)in the Lower Cretaceous McMurray Formation of Alberta.Canada.We compare the data to trends defined along the FTT in the present-day Fraser River in British Columbia.Canada to interpret paleo-depositional position in the ancient fluvial-tidal channels.Analysis determined that the mean mudstone thickness is 8.2 cm in the southern study area(SA).Mean thickness increases to 11 cm in the central study area(CA),and decreases again to 4.4 cm in the northern study area(NA).The proportion of mudstone is 31%in SA,44%in CA,and 27%in NA.Thicknessweighted mean bioturbation intensity in sands varied from 0.29 in SA and CA.to 0.28 in NA.On the other hand,thickness-weighted mean bioturbation intensity(Bl)in mudstone increases from 1.46 in SA.to 1.77 in CA.and is 1.94 in NA.The ichnological diversity also increased from south to north.Sedimentological results show sinilar trends to those of the Fraser River,enabling the identification of a freshwater to brackish-water transition zone with tidal influence.The interpreted position of the transition is underpinned by the bioturbation intensity and trace-fossil diversity trends,indicating periodic brackish-water conditions throughout SA in the McMurray Formation during low river flow conditions.Together,these data suggest that a broad FTT existed in the"A"Valley,with fluvial-dominated channels to the south that experienced seasonal brackish-water inundation during base flow,and channels experiencing increasing brackish-water influence lying further north towards a turbidity maximun zone.The FIT zone appears to have extended for several hundred kilometers fron south to north.Based on the sedimentological and ichnological data,as well as estimations of lateral accretion rates,we refute the colmonly applied Mississippi River depositional analogue for McMurray Formation channels.Rather,we show that while not a perfect fit,the tidally influenced Fraser River shows much greater agreement with the depositional character recorded in McMurray Formation IHS.Future work on the McMurray system should focus on characterizing tide-dominatecl deltaic and estuarine systems,such as the Ganges-Brahmaputra,and on forward-modeling the evolution of tide-dominated and tideinfluenced river systems.

Development of a spring analogue approach for the study of pillars and shafts

In civil and mining operations that involve ground excavation and support, the loads are distributed between the ground and support depending on their relative stiffness. This paper presents the development of conceptual single-degree-of-freedom models, which are used to derive equations for estimating displacements and stresses for ground-support interaction problems encountered in pillars in room-andpillar mining(natural support system), and liners for circular vertical shafts(artificial support systems).For pillar assessment, mine-pillar interaction curves can be constructed using a double spring analogy.Additionally, the effectiveness of different support systems can be evaluated depending on their effect upon the mine-pillar system. For shaft design, an initial estimation of the required lining strength and thickness can be readily made based on a double ring analogue. For both problems, the results from the proposed approach compare well with those obtained by finite element numerical simulations.

2D-QSAR Studies on the Norcantharidin Analogues as Protein Phosphatase 1 and 2A Inhibitors

The Two-dimensional Quantitative Structure-activity Relationship （2D-QSAR） of a series of novel norcantharidin analogues, which exhibit hnhibitory activities of protein phosphatase 1 and 2A （PP1 and PP2A）, has been studied with a combined method of ab initio （I/F）, molecular mechanics （MM＋） and statistics. The established 2D-QSAR model （Eq. 1） for PP1 shows a reasonable regressive performance （R2= 0.749）, and the hydrophobic property of this molecule plays a decisive role in determining the inhibitory activity of PP1. In addition, the established 2D-QSAR model （Eq. 2） for PP2A also shows an acceptable regressive performance （R2= 0.701）, and the dipole moment of the molecule determines the inhibitory activity of PP2A.

Is it possible to stop nucleos(t)ide analogue treatment in chronic hepatitis B patients?

Chronic hepatitis B(CHB) remains a challenging global health problem, with nearly one million related deaths per year. Nucleos(t)ide analogue(NA) treatment suppresses viral replication but does not provide complete cure of the hepatitis B virus(HBV) infection. The accepted endpoint for therapy is the loss of hepatitis B surface antigen(HBs Ag), but this is hardly ever achieved. Therefore, indefinite treatment is usually required. Many different studies have evaluated NA therapy discontinuation after several years of NA treatment and before HBs Ag loss. The results have indicated that the majority of patients can remain off therapy, with some even reaching HBs Ag seroconversion. Fortunately, this strategy has proved to be safe, but it is essential to consider the risk of liver damage and other comorbidities and to ensure aclose follow-up of the candidates before considering this strategy. Unanswered questions remain, namely in which patients could this strategy be effective and what is the optimal time point at which to perform it. To solve this enigma, we should keep in mind that the outcome will ultimately depend on the equilibrium between HBV and the host's immune system. Viral parameters that have been described as good predictors of response in HBe Ag(+) cases, have proven useless in HBe Ag(-) ones. Since antiviral immunity plays an essential role in the control of HBV infection, we sought to review and explain potential immunological biomarkers to predict safe NA discontinuation in both groups.