Anti-PD1 antibody and not anti-LAG-3 antibody improves the antitumor effect of photodynamic therapy for treating metastatic breast cancer

Photodynamic therapy(PDT)has limited effects in treating metastatic breast cancer.Immune checkpoints can deplete the function of immune cells;however,the expression of immune checkpoints after PDT is unclear.This study investigates whether the limited e±cacy of PDT is due to upregulated immune checkpoints and tries to combine the PDT and immune checkpoint inhibitor to observe the e±cacy.A metastatic breast cancer model was treated by PDT mediated by hematoporphyrin derivatives(HpD-PDT).The anti-tumor effect of HpD-PDT was observed,as well as CD4þT,CD8þT and calreticulin(CRT)by immunohistochemistry and immunofluorescence.Immune checkpoints on T cells were analyzed byflow cytometry after HpD-PDT.When combining PDT with immune checkpoint inhibitors,the antitumor effect and immune effect were assessed.For HpD-PDT at 100 mW/cm2 and 40,60 and 80 J/cm2,primary tumors were suppressed and CD4þT,CD8þT and CRT were elevated;however,distant tumors couldn't be inhibited and survival could not be prolonged.Immune checkpoints on T cells,especially PD1 and LAG-3 after HpD-PDT,were upregulated,which may explain the reason for the limited HpD-PDT effect.After PDT combined with anti-PD1 antibody,but not with anti-LAG-3 antibody,both the primary and distant tumors were signi-cantly inhibited and the survival time was prolonged,additionally,CD4þT,CD8þT,IFN-þCD4þT and TNF-þCD4þT cells were signi-cantly increased compared with HpD-PDT.HpD-PDT could not combat metastatic breast cancer.PD1 and LAG-3 were upregulated after HpD-PDT.Anti-PD1 antibody,but not anti-LAG-3 antibody,could augment the antitumor effect of HpD-PDT for treating metastatic breast cancer.

Synergistic coupling among Mg_(2)B_(2)O_(5),polycarbonate and N,Ndimethylformamide enhances the electrochemical performance of PVDF-HFP-based solid electrolyte

Polymer solid electrolytes(SPEs)based on the[solvate-Li+]complex structure have promising prospects in lithium metal batteries(LMBs)due to their unique ion transport mechanism.However,the solvation structure may compromise the mechanical performance and safety,hindering practical application of SPEs.In this work,a composite solid electrolyte(CSE)is designed through the organic-inorganic syner-gistic interaction among N,N-dimethylformamide(DMF),polycarbonate(PC),and Mg_(2)B_(2)O_(5) in poly(vinylidene fluoride-co-hexafluoropropylene)(PVDF-HFP).Flame-retardant Mg_(2)B_(2)O_(5) nanowires provide non-flammability to the prepared CSEs,and the addition of PC improves the dispersion of Mg_(2)B_(2)O_(5) nanowires.Simultaneously,the organic-inorganic synergistic action of PC plasticizer and Mg_(2)B_(2)O_(5) nanowires pro-motes the dissociation degree of LiTFSI and reduces the crystallinity of PVDF-HFP,enabling rapid Li ion transport.Additionally,Raman spectroscopy and DFT calculations confirm the coordination between Mg atoms in Mg_(2)B_(2)O_(5) and N atoms in DMF,which exhibits Lewis base-like behavior attacking adjacent C-F and C-H bonds in PVDF-HFP while inducing dehydrofluorination of PVDF-HFP.Based on the syner-gistic coupling of Mg_(2)B_(2)O_(5),PC,and DMF in the PVDF-HFP matrix,the prepared CSE exhibits superior ion conductivity(9.78×10^(-4) s cm^(-1)).The assembled Li symmetric cells cycle stably for 3900 h at a current density of 0.1 mA cm^(-2) without short circuit.The LFP||Li cells assembled with PDL-Mg_(2)B_(2)O_(5)/PC CSEs show excellent rate capability and cycling performance,with a capacity retention of 83.3%after 1000 cycles at 0.5 C.This work provides a novel approach for the practical application of organic-inorganic Synergistic CSEs in LMBs.

Two Stages Segmentation Algorithm of Breast Tumor in DCE-MRI Based on Multi-Scale Feature and Boundary Attention Mechanism

Nuclearmagnetic resonance imaging of breasts often presents complex backgrounds.Breast tumors exhibit varying sizes,uneven intensity,and indistinct boundaries.These characteristics can lead to challenges such as low accuracy and incorrect segmentation during tumor segmentation.Thus,we propose a two-stage breast tumor segmentation method leveraging multi-scale features and boundary attention mechanisms.Initially,the breast region of interest is extracted to isolate the breast area from surrounding tissues and organs.Subsequently,we devise a fusion network incorporatingmulti-scale features and boundary attentionmechanisms for breast tumor segmentation.We incorporate multi-scale parallel dilated convolution modules into the network,enhancing its capability to segment tumors of various sizes through multi-scale convolution and novel fusion techniques.Additionally,attention and boundary detection modules are included to augment the network’s capacity to locate tumors by capturing nonlocal dependencies in both spatial and channel domains.Furthermore,a hybrid loss function with boundary weight is employed to address sample class imbalance issues and enhance the network’s boundary maintenance capability through additional loss.Themethod was evaluated using breast data from 207 patients at RuijinHospital,resulting in a 6.64%increase in Dice similarity coefficient compared to the benchmarkU-Net.Experimental results demonstrate the superiority of the method over other segmentation techniques,with fewer model parameters.

Coin-structured tunable beam shaping assembly design for accelerator-based boron neutron capture therapy for tumors at different depths and sizes

In the past decade,boron neutron capture therapy utilizing an accelerator-based neutron source(ABNS)designed primarily for producing epithermal neutrons has been implemented in the treatment of brain tumors and other cancers.The specifications for designing an epithermal beam are primarily based on the IAEA-TECODC-1223 report,issued in 2001 for reactor neutron sources.Based on this report,the latest perspectives and clinical requirements,we designed an ABNS capable of adjusting the average neutron beam energy.The design was based on a 2.8 MeV,20 mA proton beam bombarding a lithium target to produce neutrons that were subsequently moderated and tuned through a tunable beam shaping assembly(BSA)which can modify the thicknesses and materials of the coin-shaped moderators,back reflectors,filters,and collimators.The simulation results demonstrated that epithermal neutron beams for deep seated tumor treatment,which were generated by utilizing magnesium fluoride with lengths ranging between 28 and 36 cm as the moderator,possessed a treatment depth of 5.6 cm although the neutron flux peak shifts from 4.5 to 1.0 keV.When utilizing a thinner moderator,a less accelerated beam power can meet the treatment requirements.However,higher powers reduced the treatment time.In contrast,employing a thick moderator can reduce the skin dose.In scenarios that required relatively low energy neutron beams,the removal of the thermal neutron filter can raise the thermal neutron flux at the beam port.And the depth of the dose rate peak could be adjusted between 0.25 and 2.20 cm by combining magnesium fluoride and polyethylene coins of different thicknesses.Hence,this device has a better adaptability for the treatment of superficial tumors.Overall,the tunable BSA provides greater flexibility for clinical treatment than common BSA designs that can only adjust the port size.

Colorectal motility patterns and psychiatric traits in functional constipation and constipation-predominant irritable bowel syndrome:A study from China

BACKGROUND Functional constipation(FC)and constipation-predominant irritable bowel syndrome(IBS-C)represent a spectrum of constipation disorders.However,the majority of previous clinical investigations have focused on Western populations,with limited data originating from China.AIM To determine and compare the colorectal motility and psychiatric features of FC and IBS-C in an Eastern Chinese population.METHODS Consecutive chronic constipation patients referred to our motility clinic from December 2019 to February 2023 were enrolled.FC and IBS-C diagnoses were established using ROME IV criteria,and patients underwent high-resolution anorectal manometry(ARM)and a colonic transmit test using the Sitz marker study.Constipation-related symptoms were obtained through questionnaires.Anxiety and depression were assessed by the Hamilton anxiety rating scale and the Hamilton Depression Rating Scale-21.The clinical characteristics and colorectal motility patterns of FC and IBS-C patients were compared.RESULTS No significant differences in sex,age or abdominal discomfort symptoms were observed between IBS-C and FC patients(all P>0.05).The proportion of IBS-C patients with delayed colonic transit was higher than that of patients with FC(36.63%vs 15.91%,P<0.05),while rectosigmoid accumulation of radiopaque markers was more common in the FC group than in the IBS-C group(50%vs 26.73%,P<0.05).Diverse proportions of these dyssynergic patterns were noted within both the FC and IBS-C groups by ARM.IBS-C patients were found to have a higher prevalence of depression than FC patients(66.30%vs 42.42%,P<0.05).The scores for feelings of guilt,suicide,psychomotor agitation,diurnal variation,obsessive/compulsive disorder,hopelessness,self-abasedment and gastrointestinal symptoms were significantly higher in IBS-C patients than that in FC patients(P<0.05).For IBS-C(χ^(2)=5.438,P<0.05)but not FC,patients with normal colon transit time were significantly more likely to have anxiety than those with slow colon transit time.For IBS-C patients but not FC patients,the threshold of first constant sensation,desire to defecate and sustained urgency were all weakly correlated with the degree of anxiety(r=0.414,r=0.404,and r=0.418,respectively,P<0.05).The proportion of patients with a low threshold of desire to defecate among IBS-C patients with depression was lower than that in those without depression(69.6%vs 41.9%,χ2=4.054,P<0.05).CONCLUSION Our findings highlight both overlapping and distinctive patterns of colon transit,dyssynergic patterns,anorectal sensation,psychological distress,and associations of psychiatric and colorectal motility characteristics in FC and IBS-C patients in an Eastern Chinese population,providing valuable insights into the pathophysiological underpinnings of these disorders.

A data-driven model of drop size prediction based on artificial neural networks using small-scale data sets

An artificial neural network(ANN)method is introduced to predict drop size in two kinds of pulsed columns with small-scale data sets.After training,the deviation between calculate and experimental results are 3.8%and 9.3%,respectively.Through ANN model,the influence of interfacial tension and pulsation intensity on the droplet diameter has been developed.Droplet size gradually increases with the increase of interfacial tension,and decreases with the increase of pulse intensity.It can be seen that the accuracy of ANN model in predicting droplet size outside the training set range is reach the same level as the accuracy of correlation obtained based on experiments within this range.For two kinds of columns,the drop size prediction deviations of ANN model are 9.6%and 18.5%and the deviations in correlations are 11%and 15%.

基于活性炭‖Na_(0.44)MnO_(2)的低成本、高倍率和长寿命碱性钠离子电池电容器

水系钠离子电池电容器具有成本低、功率大、安全性好等优点,是下一代大规模储能系统的理想选择之一。本文采用Na_(0.44)MnO_(2)正极、活性炭(AC)负极、6mol·L^(-1)NaOH电解液和廉价的不锈钢集流体构建了可充电碱性钠离子电池电容器。由于Na_(0.44)MnO_(2)正极在碱性电解液中具有较高的过充耐受性,通过首次充电时的原位过充预活化过程可以解决半钠化Na_(0.44)MnO_(2)正极和AC负极初始库伦效率低的缺点。因此,AC‖Na_(0.44)MnO_(2)可充电碱性钠离子电池电容器具有优异的电化学性能,在功率密度为85 W·kg^(-1)时,能量密度达26.6 Wh·kg^(-1),循环10000次后容量保持率为89%。同时,在50℃的高温和-20℃的低温也具有良好的电化学性能。这些结果表明AC‖Na_(0.44)MnO_(2)可充电碱性钠离子电池电容器具备应用于大规模储能的潜力。

High corrosion and wear resistant electroless Ni–P gradient coatings on aviation aluminum alloy parts

A Ni–P alloy gradient coating consisting of multiple electroless Ni–P layers with various phosphorus contents was prepared on the aviation aluminum alloy. Several characterization and electrochemical techniques were used to characterize the different Ni–P coatings’ morphologies, phase structures, elemental compositions, and corrosion protection. The gradient coating showed good adhesion and high corrosion and wear resistance, enabling the application of aluminum alloy in harsh environments. The results showed that the double zinc immersion was vital in obtaining excellent adhesion (81.2 N). The optimal coating was not peeled and shredded even after bending tests with angles higher than 90°and was not corroded visually after 500 h of neutral salt spray test at 35℃. The high corrosion resistance was attributed to the misaligning of these micro defects in the three different nickel alloy layers and the amorphous structure of the high P content in the outer layer. These findings guide the exploration of functional gradient coatings that meet the high application requirement of aluminum alloy parts in complicated and harsh aviation environments.

Vitamin A regulates mitochondrial biogenesis and function through p38 MAPK‑PGC‑1α signaling pathway and alters the muscle fiber composition of sheep

Background Vitamin A(VA)and its metabolite,retinoic acid(RA),are of great interest for their wide range of physiological functions.However,the regulatory contribution of VA to mitochondrial and muscle fiber composition in sheep has not been reported.Method Lambs were injected with 0(control)or 7,500 IU VA palmitate into the biceps femoris muscle on d 2 after birth.At the age of 3 and 32 weeks,longissimus dorsi(LD)muscle samples were obtained to explore the effect of VA on myofiber type composition.In vitro,we investigated the effects of RA on myofiber type composition and intrinsic mechanisms.Results The proportion of type I myofiber was greatly increased in VA-treated sheep in LD muscle at harvest.VA greatly promoted mitochondrial biogenesis and function in LD muscle of sheep.Further exploration revealed that VA elevated PGC-1αmRNA and protein contents,and enhanced the level of p38 MAPK phosphorylation in LD muscle of sheep.In addition,the number of type I myofibers with RA treatment was significantly increased,and type IIx myofibers was significantly decreased in primary myoblasts.Consistent with in vivo experiment,RA significantly improved mitochondrial biogenesis and function in primary myoblasts of sheep.We then used si-PGC-1αto inhibit PGC-1αexpression and found that si-PGC-1αsignificantly abrogated RA-induced the formation of type I myofibers,mitochondrial biogenesis,MitoTracker staining intensity,UQCRC1 and ATP5A1 expression,SDH activity,and enhanced the level of type IIx muscle fibers.These data suggested that RA improved mitochondrial biogenesis and function by promoting PGC-1αexpression,and increased type I myofibers.In order to prove that the effect of RA on the level of PGC-1αis caused by p38 MAPK signaling,we inhibited the p38 MAPK signaling using a p38 MAPK inhibitor,which significantly reduced RA-induced PGC-1αand MyHC I levels.Conclusion VA promoted PGC-1αexpression through the p38 MAPK signaling pathway,improved mitochondrial biogenesis,and altered the composition of muscle fiber type.

High donor-number and low content electrolyte additive for stabilizing zinc metal anode

The aqueous zinc ion batteries(AZIBs)are thought as promising competitors for electrochemical energy storage,though their wide application is curbed by the uncontrollable dendrite growth and gas evolution side reactions.Herein,to stabilize both zinc anodes and water molecules,we developed a modified electrolyte by adding a trace amount of N,N-diethylformanmide(DEF)into the ZnSO_(4)electrolyte for the first time in zinc ion batteries.The effectiveness of DEF is predicted by the comparison of donor number and its preferential adsorption behavior on the zinc anode is further demonstrated by several spectroscopy characterizations,electrochemical methods,and molecular dynamics simulation.The modified electrolyte with 5%v.t.DEF content can ensure a stable cycling life longer than 3400 h of Zn‖Zn symmetric cells and an ultra-reversible Zn stripping/plating process with a high coulombic efficiency of 99.7%.The Zn‖VO_(2)full cell maintains a capacity retention of 83.5%and a 104 mA h g^(-1)mass capacity after 1000cycles.This work provides insights into the role of interfacial adsorption behavior and the donor number of additive molecules in designing low-content and effective aqueous electrolytes.

MXene-Based Elastomer Mimetic StretchableSensors: Design, Properties, and Applications

Flexible sensors based on MXene-polymer composites are highly prospective for next-generation wearable electronics used in human-machine interfaces.One of the motivating factors behind the progress of flexible sensors is the steady arrival of new conductive materials.MXenes,a new family of 2D nanomaterials,have been draw-ing attention since the last decade due to their high electronic conduc-tivity,processability,mechanical robustness and chemical tunability.In this review,we encompass the fabrication of MXene-based polymeric nanocomposites,their structure-property relationship,and applications in the flexible sensor domain.Moreover,our discussion is not only lim-ited to sensor design,their mechanism,and various modes of sensing platform,but also their future perspective and market throughout the world.With our article,we intend to fortify the bond between flexible matrices and MXenes thus promoting the swift advancement of flexible MXene-sensors for wearable technologies.

Noise-Tolerant ZNN-Based Data-Driven Iterative Learning Control for Discrete Nonaffine Nonlinear MIMO Repetitive Systems

Aiming at the tracking problem of a class of discrete nonaffine nonlinear multi-input multi-output(MIMO) repetitive systems subjected to separable and nonseparable disturbances, a novel data-driven iterative learning control(ILC) scheme based on the zeroing neural networks(ZNNs) is proposed. First, the equivalent dynamic linearization data model is obtained by means of dynamic linearization technology, which exists theoretically in the iteration domain. Then, the iterative extended state observer(IESO) is developed to estimate the disturbance and the coupling between systems, and the decoupled dynamic linearization model is obtained for the purpose of controller synthesis. To solve the zero-seeking tracking problem with inherent tolerance of noise,an ILC based on noise-tolerant modified ZNN is proposed. The strict assumptions imposed on the initialization conditions of each iteration in the existing ILC methods can be absolutely removed with our method. In addition, theoretical analysis indicates that the modified ZNN can converge to the exact solution of the zero-seeking tracking problem. Finally, a generalized example and an application-oriented example are presented to verify the effectiveness and superiority of the proposed process.

Deciphering the population structure and genetic basis of growth traits from whole-genome resequencing of the leopard coral grouper(Plectropomus leopardus)

The leopard coral grouper(Plectropomus leopardus)is a species of significant economic importance.Although artificial cultivation of P.leopardus has thrived in recent decades,the advancement of selective breeding has been hindered by the lack of comprehensive population genomic data.In this study,we identified over 8.73 million single nucleotide polymorphisms(SNPs)through whole-genome resequencing of 326 individuals spanning six distinct groups.Furthermore,we categorized 226 individuals with high-coverage sequencing depth(≥14×)into eight clusters based on their genetic profiles and phylogenetic relationships.Notably,four of these clusters exhibited pronounced genetic differentiation compared with the other populations.To identify potentially advantageous loci for P.leopardus,we examined genomic regions exhibiting selective sweeps by analyzing the nucleotide diversity(θπ)and fixation index(FST)in these four clusters.Using these high-coverage resequencing data,we successfully constructed the first haplotype reference panel specific to P.leopardus.This achievement holds promise for enabling high-quality,cost-effectiveimputationmethods.Additionally,we combined low-coverage sequencing data with imputation techniques for a genome-wide association study,aiming to identify candidate SNP loci and genes associated with growth traits.A significant concentration of these genes was observed on chromosome 17,which is primarily involved in skeletal muscle and embryonic development and cell proliferation.Notably,our detailed investigation of growth-related SNPs across the eight clusters revealed that cluster 5 harbored the most promising candidate SNPs,showing potential for genetic selective breeding efforts.These findings provide a robust toolkit and valuable insights into the management of germplasm resources and genome-driven breeding initiatives targeting P.leopardus.

Enterococcus faecalis provides protection during scavenging in carrion crow (Corvus corone)

The gut microbiota significantly influences host physiology and provides essential ecosystem services.While diet can affect the composition of the gut microbiota,the gut microbiota can also help the host adapt to specific dietary habits.The carrion crow(Corvus corone),an urban facultative scavenger bird,hosts an abundance of pathogens due to its scavenging behavior.Despite this,carrion crows infrequently exhibit illness,a phenomenon related to their unique physiological adaptability.At present,however,the role of the gut microbiota remains incompletely understood.In this study,we performed a comparative analysis using 16S rRNA amplicon sequencing technology to assess colonic content in carrion crows and 16 other bird species with different diets in Beijing,China.Our findings revealed that the dominant gut microbiota in carrion crows was primarily composed of Proteobacteria(75.51%)and Firmicutes(22.37%).Significant differences were observed in the relative abundance of Enterococcus faecalis among groups,highlighting its potential as a biomarker of facultative scavenging behavior in carrion crows.Subsequently,E.faecalis isolated from carrion crows was transplanted into model mice to explore the protective effects of this bacterial community against Salmonella enterica infection.Results showed that E.faecalis down-regulated the expression of pro-inflammatory cytokines tumor necrosis factor alpha(TNF-α),interferon gamma(IFN-γ),and interleukin 6(IL-6),prevented S.enterica colonization,and regulated the composition of gut microbiota in mice,thereby modulating the host’s immune regulatory capacity.Therefore,E.faecalis exerts immunoregulatory and anti-pathogenic functions in carrion crows engaged in scavenging behavior,offering a representative case of how the gut microbiota contributes to the protection of hosts with specialized diets.

Animal models of eosinophilic esophagitis,review and perspectives

Eosinophilic oesophagitis(EoE)is an allergen/immune-mediated chronic esophageal disease characterized by esophageal mucosal eosinophilic infiltration and esophageal dysfunction.Although the disease was originally attributed to a delayed allergic reaction to allergens and a Th2-type immune response,the exact pathogenesis is complex,and the efficacy of existing treatments is unsatisfactory.Therefore,the study of the pathophysiological process of EOE has received increasing attention.Animal models have been used extensively to study the molecular mechanism of EOE pathogenesis and also provide a preclinical platform for human clinical intervention studies of novel therapeutic agents.To maximize the use of existing animal models of EOE,it is important to understand the advantages or limitations of each modeling approach.This paper systematically describes the selection of experimental animals,types of allergens,and methods of sensitization and excitation during the preparation of animal models of EoE.It also discusses the utility and shortcomings of each model with the aim of providing the latest perspectives on EoE models and leading to better choices of animal models.

Inhibiting the phase transition of WO_(3)for highly stable aqueous electrochromic battery

Aqueous electrochromic battery(ECB)has shown intense potential for achieving energy storage and saving simultaneously.While tungsten oxide(WO_(3))is the most promising EC material for commercialization,the cycling stability of WO_(3)-based aqueous ECBs is currently unsatisfactory due to the repeated phase transition during the redox process and the corrosion by acidic electrolytes.Herein,we present a titanium-tungsten oxide alloy(Ti-WO_(3))with controllable morphology and crystal phase synthesized by a facile hot injection method to overcome the challenges.In contrast to conventional monoclinic WO_(3),the Ti-WO_(3)nanorods can stably maintain their cubic crystal phase during the redox reaction in an acidic electrolyte,thus leading to dramatically enhanced response speed and cycling stability,Specifically,when working in a well-matched hybrid Al^(3+)/Zn^(2+)aqueous electrolyte,our phasetransition-free cubic Ti-WO_(3)exhibits an ultra-high cycling stability(>20000 cycles),fast response speed(3,95 s/4,65 s for bleaching/coloring),as well as excellent discharge areal capacity of 214.5 mA h m^(-2),We further fabricate a fully complementa ry aqueous electrochromic device,for the first time,using a Ti-WO_(3)/Prussian blue device architecture.Remarkably,the complementary ECB shows>10000 stable operation cycles,attesting to the feasibility of our Ti-WO_(3)for practical applications.Our work validates the significance of inhibiting the phase transitions of WO_(3)during the electrochromic process for realizing highly cyclable aqueous ECB,which can possibly provide a generalized design guidance for other high-quality metallic oxides for electrochemical applications.

A step to the decentralized real-time timekeeping network

The composite time scale(CTS) provides an accurate and stable time-frequency reference for modern science and technology. Conventional CTS always features a centralized network topology, which means that the CTS is accompanied by a local master clock. This largely restricts the stability and reliability of the CTS. We simulate the restriction and analyze the influence of the master clock on the CTS. It proves that the CTS's long-term stability is also positively related to that of the master clock, until the region dominated by the frequency drift of the H-maser(averaging time longer than ~10~5s).Aiming at this restriction, a real-time clock network is utilized. Based on the network, a real-time CTS referenced by a stable remote master clock is achieved. The experiment comparing two real-time CTSs referenced by a local and a remote master clock respectively reveals that under open-loop steering, the stability of the CTS is improved by referencing to a remote and more stable master clock instead of a local and less stable master clock. In this way, with the help of the proposed scheme, the CTS can be referenced to the most stable master clock within the network in real time, no matter whether it is local or remote, making democratic polycentric timekeeping possible.

Synthesis of betanin by expression of the core betalain biosynthetic pathway in carrot

Betalain has received increased attention because of its high nutritional value and crucial physiological functions.Based on the elucidation of its core biosynthetic pathway,betalain can be produced in additional plants by metabolic engineering.Synthesis of betalain in carrot(Daucus carota L.)can improve its nutritional quality and economic value by extracting betalain from the fleshy root,non-edible part,and processing residue of carrot.In this study,two different constructs,namely,pYB:mCD(AomelOS,BvCYP76AD1S,and BvDODA1S)and p YB:CDD(BvCYP76AD1S,BvDODA1S,and MjcDOPA5GTS),were introduced into carrot for betanin synthesis by Agrobacterium-mediated transformation.Betanin can be synthetized in both transgenic calli,and p YB:m CD-transgenic callus can be used to produce betacyanin by suspension culture.However,pYB:mCD-transgenic seedlings can synthetize betanin only by tyrosine feeding.The p YB:CDD-transgenic lines can synthetize betanin in whole plants.The betanin content in fleshy root of pYB:CDD-transgenic carrot was(63.4±9)μg·g^(-1)fresh weight according to quantitative analysis.These betanin-producing carrot plant materials can be used to synthesize betanin for industrial application or consumption as dietary sources.

Gastrointestinal manifestations of critical ill heatstroke patients and their associations with outcomes:A multicentre,retrospective,observational study

BACKGROUND Extreme heat exposure is a growing health problem,and the effects of heat on the gastrointestinal(GI)tract is unknown.This study aimed to assess the incidence of GI symptoms associated with heatstroke and its impact on outcomes.AIM To assess the incidence of GI symptoms associated with heatstroke and its impact on outcomes.METHODS Patients admitted to the intensive care unit(ICU)due to heatstroke were included from 83 centres.Patient history,laboratory results,and clinically relevant outcomes were recorded at ICU admission and daily until up to day 15,ICU discharge,or death.GI symptoms,including nausea/vomiting,diarrhoea,flatulence,and bloody stools,were recorded.The characteristics of patients with heatstroke concomitant with GI symptoms were described.Multivariable regression analyses were performed to determine significant predictors of GI symptoms.RESULTS A total of 713 patients were included in the final analysis,of whom 132(18.5%)patients had at least one GI symptom during their ICU stay,while 26(3.6%)suffered from more than one symptom.Patients with GI symptoms had a significantly higher ICU stay compared with those without.The mortality of patients who had two or more GI symptoms simultaneously was significantly higher than that in those with one GI symptom.Multivariable logistic regression analysis revealed that older patients with a lower GCS score on admission were more likely to experience GI symptoms.CONCLUSION The GI manifestations of heatstroke are common and appear to impact clinically relevant hospitalization outcomes.

Perioperative remedial antiviral therapy in hepatitis B virus-related hepatocellular carcinoma resection:How to achieve a better outcome

BACKGROUND Although the benefits of antiviral therapy for hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC)have been proven,researchers have not con-firmed the differences in patient outcomes between patients who received preoperative antiviral therapy for a period of time(at least 24 wk)and patients who received remedial antiviral therapy just before radical resection for HBV-related HCC.AIM To investigate the efficacy of perioperative remedial antiviral therapy in patients with HBV-related HCC.METHODS A retrospective study of patients who underwent radical resection for HBV-related HCC at the First Affiliated Hospital of Xi’an Jiaotong University from January 2016 to June 2019 was conducted.Considering the history of antiviral therapy,patients were assigned to remedial antiviral therapy and preoperative antiviral therapy groups.RESULTS Kaplan–Meier analysis revealed significant differences in overall survival(P<0.0001)and disease-free survival(P=0.035)between the two groups.Multivariate analysis demonstrated that a history of preoperative antiviral treatment was independently related to improved survival(hazard ratio=0.27;95%confidence interval:0.08-0.88;P=0.030).CONCLUSION In patients with HBV-related HCC,it is ideal to receive preoperative long-term antiviral therapy,which helps patients tolerate more extensive hepatectomy;however,remedial antiviral therapy,which reduces preoperative HBV-DNA levels to less than 4 Log10 copies DNA/mL,can also result in improved outcomes.