Studies on the motion and radiation of interior plasmas in gas-filled hohlraums with different laser entrance hole sizes

An experiment on 100 k J laser facility is performed to study the motive features and radiation properties of plasmas from different areas inside gas-filled cylindrical hohlraums.These hohlraums are designed to possess one open end and one laser entrance hole(LEH)with different diameters,which would or not result in the blocking of the LEH.An x-ray streak camera that is set at 16 degrees with respect to the hohlraum axis is applied to acquire the timeresolved x-ray images from the open end.Based on the images,we can study the evolutions of the wall plasma,corona bubble plasma and LEH plasma simultaneously through an equivalent view field of hohlraum interior.Multi-group flat response x-ray detectors are applied to measure the x-ray fluxes.In order to understand these characteristics,our two-dimensional radiation hydrodynamic code is used to simulate the experimental results.For the accuracy of reproduction,dielectronic recombination and two parameter corrections are applied in our code.Based on the comparison between experiments and simulations,we quantitatively understand the blocking process of LEH and the motion effects of other plasmas.The calibrated code is beneficial to design the gas-filled hohlraum in a nearby parameter space,especially the limit size of LEH.

Self-consistent and precise measurement of time-dependent radiative albedo of gold based on specially symmetrical triple-cavity Hohlraum

A self-consistent and precise method to determine the time-dependent radiative albedo,i.e.,the ratio of the reemission flux to the incident flux,for an indirect-drive inertial confinement fusion Hohlraum wall material is proposed.A specially designed symmetrical triple-cavity gold Hohlraum is used to create approximately constant and near-equilibrium uniform radiation with a peak temperature of 160 eV.The incident flux at the secondary cavity waist is obtained from flux balance analysis and from the shock velocity of a standard sample.The results agree well owing to the symmetrical radiation in the secondary cavity.A self-consistent and precise time-dependent radiative albedo is deduced from the reliable reemission flux and the incident flux,and the result from the shock velocity is found to have a smaller uncertainty than that from the multi-angle flux balance analysis,and also to agree well with the result of a simulation using the HYADES opacity.

Seven-years post allogeneic hematopoietic stem cell transplantation pure red cell aplastic anemia cured with daratumumab:A case report and review of literature

BACKGROUND Allogeneic hematopoietic stem cell transplantation(Allo-HSCT)is currently the only viable method of curing patients with acute myeloid leukaemia.In 30%to 50%of patients,donors and recipients have some level of ABO blood group incompatibility.ABO blood group incompatibility can cause antibodies against the donor's red blood cells to persist in the recipient's body,resulting in a delay of several months in the recovery of red blood cells.A number of different treatments have been reported for post-transplant pure red cell aplastic anaemia(PRCA),such as plasmapheresis,donor lymphocyte infusions,anti-thymocyte globulin,rituximab and steroids.CASE SUMMARY A 41-year-old female diagnosed with acute myeloid leukaemia underwent peripheral blood allogeneic haematopoietic stem cell transplantation in November 2013 from an HLA matched unrelated donor.The donor was AB-positive and the recipient was O-positive.The patient was diagnosed with PRCA three months after receiving the donor stem cell transplant.After failing multiple lines of therapy,the patient applied for daratumumab.After receiving three doses of daratumumab,the patient developed a reticulocyte response and no longer required CONCLUSION The use of daratumumab anti-CD38 for the remove of plasma cells is safe and effective and may be tried for refractory patients with PRCA after undergoing allo-HSCT for ABO incompatibility.

Clinical Practice of Evidence-Based PDCA Cycle Management Model in Accelerated Recovery of Lung Cancer Patients

Objective: To explore the nursing effect of evidence-based PDCA cycle management mode in accelerated rehabilitation of patients undergoing thoracoscopic lung cancer radical surgery. Methods: 104 patients who underwent thoracoscopic lung cancer radical surgery in our hospital from June 2022 to February 2023 were randomly divided into control group and intervention group, with 52 cases in each group. The control group implemented evidence-based ERAS clinical pathway management, while the intervention group implemented evidence-based PDCA cycle quality management. The postoperative recovery of the two groups of patients was compared. Results: The postoperative recovery of the intervention group was significantly better than that of the control group. The first time to get out of bed, the first time to eat, the duration of chest drainage tube placement, and the length of hospital stay were significantly shorter than those of the control group. The incidence of postoperative chest complications and hospitalization costs were significantly lower than those of the control group, and patient satisfaction was significantly higher than that of the control group (P Conclusion: Evidence-based PDCA cycle quality management mode can effectively improve the implementation quality of accelerated rehabilitation nursing for patients undergoing thoracoscopic lung cancer radical surgery, and it is worthy of clinical promotion.

电磁导航支气管镜活检联合Massage染色定位在肺疾病诊疗中的应用

背景与目的电磁导航支气管镜(electromagnetic navigation bronchoscope, ENB)因无创、准确、实时等特点,是目前最新的微创诊疗技术。本研究探讨ENB活检联合一种新颖的Massage染色定位技术在肺周围型病变(peripheral pulmonary lesion, PPL)诊治中的应用。方法回顾分析陆军军医大学大坪医院胸外科2017年8月-2018年1月施行ENB活检联合Massage染色定位的15例PPL患者的临床资料。其中,男性12例、女性3例,年龄(51.3±2.1)岁。结果 15例PPL直径6 mm-36 mm,平均14.0 mm。活检成功率66.7%。15例均成功行Massage染色定位。染色部位中心距离病灶中心(1.0±0.4)cm,染色扩散直径(2.8±0.6)cm。操作时间为(26.7±5.3)min,术中失血量(3.3±1.5)mL。操作过程中无气胸、大出血及气管损伤。结论该技术损伤小、并发症率低、精度高、一站式完成诊断及定位,值得推广。

Glycyrrhizinate reduces portal hypertension in isolated perfused rat livers with chronic hepatitis

AIM:To investigate the effects of diammonium glycyrrhizinate(Gly)on portal hypertension(PHT)in isolated portal perfused rat liver(IPPRL)with carbon tetrachloride(CCl4)-induced chronic hepatitis.METHODS:PHT model was replicated with CCl4 in rats for 84 d.Model was identified by measuring the ascetic amounts,hepatic function,portal pressure in vivo,splenic index,and pathological alterations.Inducible nitric oxide synthase(iNOS)in liver was assessed by immunohistochemistry.IPPRLs were performed at d0,d28,d56,and d84.After phenylephrine-induced constriction,Gly was geometrically used to reduce PHT.Gly action was expressed as median effective concentration(EC50)and area under the curve(AUC).Underlying mechanism was exploited by linear correlation between AUC values of Gly and existed iNOS in portal triads.RESULTS:PHT model was confirmed with ascites,splenomegaly,serum biomarkers of hepatic injury,and elevated portal pressure.Pathological findings had shown normal hepatic structure at d0,degenerations at d28,fibrosis at d56,cirrhosis at d84in PHT rats.Pseudo lobule ratios decreased and collagen ratios increased progressively along with PHT development.Gly does dose-dependently reduce PHT in IPPRLs with CCl4-induced chronic hepatitis.Gly potencies were increased gradually along with PHT development,characterized with its EC50at 2.80×10-10,3.03×10-11,3.77×10-11and 4.65×10-11mol/L at d0,d28,d56and d84,respectively.Existed iNOS was located at hepatocyte at d0,stellate cells at d28,stellate cells and macrophages at d56,and macrophages in portal triads at d84.Macrophages infiltrated more into portal triads and expressed more iNOS along with PHT development.AUC values of Gly were positively correlated with existed iNOS levels in portal triads.CONCLUSION:Gly reduces indirectly PHT in IPPRL with CCl4-induced chronic hepatitis.The underlying mechanisms may relate to rescue NO bioavailability from macrophage-derived peroxynitrite in portal triads.

Influence of genotypes and environmental factors on leaf triterpenoid content and growth of Cyclocarya paliurus

Cyclocarya paliurus, an economically valuable tree species, has traditionally been used as a nutraceutical food or medicine in China. However, limited information is available on its genotype selection and cultivation under a wide range of environmental conditions for growth and targeted health-promoting substances. We studied the effects of genotype and environment, and their interaction on leaf triterpenoid content and tree growth for 12 genotypes of C. paliurus grown at four sites. We quantified the correlation between leaf triterpenoid accumulation and tree growth. The contents of cyclocaric acid B, cyclocarioside I, and arjunolic acid ranged from 0.06 to 3.89, 0 to 3.71, and 0.65 to 8.86 mg g^-1, respectively. Three individual triterpenoids were primarily influenced by genotype (variation ranged from 53.7 to 68.0%), while environment accounted for most of the variation in total triterpenoid content and tree growth (71.3–89.5%). Most tested environmental parameters were significantly correlated to total triterpenoid content, but not to the contents of the individual triterpenoids measured. Growth in tree height and diameter at breast height were significantly negatively correlated with total triterpenoid content but were non-significantly correlated with individual triterpenoid contents. We conclude that genotypic selection, manipulation of environmental conditions, and implementation of appropriate silvicultural operations would be important strategies for increasing the accumulation of health-promoting phytochemicals.

Lesions of mediodorsal thalamic nucleus reverse abnormal firing of the medial prefrontal cortex neurons in parkinsonian rats

The dysfunction of the medial prefrontal cortex is associated with affective disorders and non-motor features in Parkinson’s disease.However,the exact role of the mediodorsal thalamic nucleus in the function of the prefrontal cortex remains unclear.To study the possible effects of the mediodorsal thalamic nucleus on the neurological function of the medial prefrontal cortex,a model of Parkinson’s disease was established by injecting 8μg 6-hydroxydopamine into the substantia nigra compacta of rats.After 1 or 3 weeks,0.3μg ibotenic acid was injected into the mediodorsal thalamic nucleus of the midbrain.At 3 or 5 weeks after the initial injury,neuronal discharge in medial prefrontal cortex of rat brain was determined electrophysiologically.The numbers of dopamine-positive neurons and tyrosine hydroxylase immunoreactivity in substantia nigra compacta and ventral tegmental area were detected by immunohistochemical staining.Results demonstrated that after injury,the immunoreactivity of dopamine neurons and tyrosine hydroxylase decreased in the substantia nigra compacta and ventral tegmental areas of rats.Compared with normal medial prefrontal cortical neurons,at 3 and 5 weeks after substantia nigra compacta injury,the discharge frequency of pyramidal neurons increased and the discharge pattern of these neurons tended to be a burst-discharge,with an increased discharge interval.The discharge frequency of interneurons decreased and the discharge pattern also tended to be a burst-discharge,but the discharge interval was only higher at 3 weeks.At 3 weeks after the combined lesions,the discharge frequency,discharge pattern and discharge interval were restored to a normal level in pyramidal neurons and interneurons in medial prefrontal cortex.These findings have confirmed that mediodorsal thalamic nucleus is involved in regulating neuronal activities of the medial prefrontal cortex.The changes in the function of the mediodorsal thalamic nucleus may be associated with the abnormal discharge activity of the medial prefrontal cortex neurons after substantia nigra compacta injury.All experimental procedures were approved by the Institutional Animal Care and Use Committee of Xi’an Jiaotong University,China(approval No.XJTULAC2017-067)on August 26,2017.

Determination of laser entrance hole size for ignition-scale octahedral spherical hohlraums

A recently proposed octahedral spherical hohlraum with six laser entrance holes(LEHs)is an attractive concept for an upgraded laser facility aiming at a predictable and reproducible fusion gain with a simple target design.However,with the laser energies available at present,LEH size can be a critical issue.Owing to the uncertainties in simulation results,the LEH size should be determined on the basis of experimental evidence.However,determination of LEH size of an ignition target at a small-scale laser facility poses difficulties.In this paper,we propose to use the prepulse of an ignition pulse to determine the LEH size for ignition-scale hohlraums via LEH closure behavior,and we present convincing evidence from multiple diagnostics at the SGIII facility with ignition-scale hohlraum,laser prepulse,and laser beam size.The LEH closure observed in our experiment is in agreement with data from the National Ignition Facility.The total LEH area of the octahedral hohlraum is found to be very close to that of a cylindrical hohlraum,thus successfully demonstrating the feasibility of the octahedral hohlraum in terms of laser energy,which is crucially important for sizing an ignition-scale octahedrally configured laser system.This work provides a novel way to determine the LEH size of an ignition target at a small-scale laser facility,and it can be applied to other hohlraum configurations for the indirect drive approach.

Dorsomorphin induces cancer cell apoptosis and sensitizes cancer cells to HSP90 and proteasome inhibitors by reducing nuclear heat shock factor 1 levels

Objective: Heat shock factor 1(HSF1), a transcriptional regulator of heat shock proteins(HSPs), is an attractive therapeutic target for cancer. However, only a few HSF1 inhibitors have been identified so far.Methods: The mRNA and protein levels of HSF1, HSPs, cleaved PARP, and phosphorylated HSF1 were examined by real-time PCR and Western blot. Forced expression, RNA interference, and immunofluorescence assay were used for mechanistic studies.Cell viability and apoptosis were measured by WST-8 assay and flow cytometry, respectively. Xenograft studies were performed in nude mice to evaluate the effect of dorsomorphin and an HSP90 inhibitor on tumor growth.Results: Dorsomorphin suppressed multiple stimuli-induced and constitutive HSPs expression in cancer cells. Mechanistic studies revealed that dorsomorphin reduced heat-induced HSP expression independent of adenosine monophosphate activated protein kinase. Dorsomorphin reduced heat-stimulated HSF1 Ser320 phosphorylation and nuclear translocation, as well as resting nuclear HSF1 levels in cancer cells. Dorsomorphin induced cancer cell apoptosis by inhibiting HSF1 expression. A structure-activity study revealed that the 4-pyridyl at the 3-site of the pyrazolo [1, 5-a]pyrimidine ring is critical for the anti-HSF1 activities of dorsomorphin. Dorsomorphin sensitized cancer cells to HSP90 and proteasome inhibitors and inhibited HSP70 expression induced by these inhibitors in vitro. In tumor-bearing nude mice, dorsomorphin enhanced HSP90 inhibitor-induced cancer cell apoptosis, tumor growth inhibition, and HSP70 expression.Conclusions: Dorsomorphin is an HSF1 inhibitor. It induces cancer cell apoptosis, sensitizes cancer cells to both HSP90 and proteasome inhibitors, and suppresses HSP upregulation by these drugs, which may prevent the development of drug resistance.Hence, dorsomorphin and its derivates may serve as potential precursors for developing drugs against cancer.

Circulating tumor cells with epithelial-mesenchymal transition markers as potential biomarkers for the diagnosis of lung cancer

BACKGROUND Circulating tumor cells(CTCs) can be clustered into three subtypes according to epithelial-mesenchymal transition(EMT) markers: CTCs with epithelial markers(E-CTCs), CTCs with mesenchymal markers(M-CTCs), and CTCs with both markers(E&M-CTCs). CTC detection has clinical implications in the diagnosis of lung cancer(LC).AIM To clarify the diagnostic value of CTCs categorized by EMT markers in LC.METHODS The study included 106 patients with lung adenocarcinoma, including 42 groundglass opacities(GGO) and 64 solid lesions, who underwent surgery between July 2015 and December 2019. Eleven patients with benign tumors and seventeen healthy controls were included. CTCs in peripheral blood and associated EMT markers were detected preoperatively using the CanPatrol TM technique. The diagnostic power of CTCs for discriminating LC cases from controls was analyzed by the receiver operating characteristic(ROC) curve. The CytoploRare technique was used in 20 cases and 18 controls for validation, and Kappa values were calculated to evaluate consistency between techniques.RESULTS Of the 106 LC cases, 94(89.6%) had at least one CTC. CTCs were detectable in 35(83.3%) of 42 GGO cases. Total CTCs and E&M-CTCs were significantly more frequent in LC cases than in benign or healthy controls. The proportion of MCTCs plus E&M-CTCs increased gradually from healthy controls, to benign controls, to LC cases. The area under the ROC curve of total CTCs and E&M-CTCs was > 0.8 and > 10.75, respectively. The combined sensitivity of total-CTCs and E&M-CTCs was 85.85% for LC patients(80.95% for GGO patients) and the specificity was 78.57%.The Kappa value was 0.415,indicating relative consistency between CanPatrol TM and CytoploRare.CONCLUSION CTC detection is valuable for distinguishing LC from controls,and particularly E&M-CTC detection warrants further study.

Bioinformatic Game Theory and Its Application to Biological Affinity Networks

The exact evolutionary history of any set of biological taxa is unknown, and all phylogenetic reconstructions are approximations. The problem becomes harder when one must consider a mix of vertical and lateral phylogenetic signals. In this paper we propose a game theoretic approach to constructing biological networks. The key hypothesis is that evolution is driven by distinct mechanisms that seek to maximize two competing objectives, taxonomic conservation and diversity. One branch of the mathematical theory of games is brought to bear. It translates this evolutionary game hypothesis into a mathematical model in two-player zero-sum games, with the zero-sum assumption conforming to one of the fundamental constraints in nature in mass and energy conservation. We demonstrate why and how a mechanistic and localized adaptation to seek out greater information for conservation and diversity may always lead to a global Nash equilibrium in phylogenetic affinity. Our game theoretic method, referred to as bioinformatic game theory, is used to construct network clusters. As an example, we applied this method to clustering of a multidomain protein family. The protein clusters identified were consistent with known protein subfamilies, indicating that this game-theoretic approach provides a new framework in biological sequence analysis, especially in studying gene-genome and domain-protein relationships.

The effects of incident light wavelength difference on the collective stimulated Brillouin scattering in plasmas

The first laser–plasma interaction experiment using lasers of eight beams grouped into one octad has been conducted on the Shenguang Octopus facility.Although each beam intensity is below its individual threshold for stimulated Brillouin backscattering(SBS),collective behaviors are excited to enhance the octad SBS.In particular,when two-color/cone lasers with wavelength separation 0.3 nm are used,the backward SBS reflectivities show novel behavior in which beams of longer wavelength achieve higher SBS gain.This property of SBS can be attributed to the rotation of the wave vectors of common ion acoustic waves due to the competition of detunings between geometrical angle and wavelength separation.This mechanism is confirmed using massively parallel supercomputer simulations with the three-dimensional laser–plasma interaction code LAP3D.

Modeling the molecular interactions of budesonide with bovine serum albumin guides the rational preparation of nanoparticles for pulmonary delivery

Large Hollow nanoparticulate aggregates（LHNAs） based on albumin nanoparticles is a promising technology for developing dry powder inhaler（DPI） with good aerodynamic properties in order to provide a new drug delivery system（DDS） for the treatment of lung disease. Improved understanding of molecular interactions could lead to prepare the DDS rationally. Therefore, this investigation utilized computations and experiments to reveal the mechanisms of budesonide（BUD） interactions with bovine serum albumin（BSA） at the molecular level. The molecular dynamics（MD） simulation revealed that there were three critical stable binding sites of BUD on BSA（P1, P2, P3） mainly by hydrophobic interaction and hydrogen bond. The energy decomposition of each residue to the whole BUD-BSA complex system in P1-P3 showed that nonpolar residues in or around the binding site played an important role in the binding of BUD to BSA. The molar ratio was close to 3 in preparations in drug-loading efficiency experiment, which was confirmed to the simulation results. The details of the binding sites from computation provided a guideline for the design of the BSA nanoparticles carrying BUD, which was prepared successfully at last. Combination of the MD simulation and experiment as well as the mechanism of the molecular interaction provided a solid theoretical basis for the preparation of BSA-LHNAs for DPI in the future.

Research Progress of Fabrics with Different Geometric Structures for Triboelectric Nanogenerators in Flexible and Wearable Electronics

Widespread reliance on fossil fuels,and the resulting imbalance between energy supply and demand have emerged as significant obstacles to achieving sustainable development.Triboelectric nanogenerators(TENGs)offer a viable solution to this problem.Among the various materials used in TENGs,fabrics with geometric structures have attracted considerable interest because of their advantageous properties,such as their light weight,breathable structures,favorable softness,and excellent breathability.This review provides a comprehensive introduction to fabric geometric(fabric structure with yarn as the basic unit,including woven fabrics formed by warp and weft yarns and knitted fabrics formed by yarn coils,etc.)TENGs,including their definition,working principle,and mechanisms,and explores the recent progress in TENGs based on one-,two-,and three-dimensional structures,classifying them into woven and knitted fabrics according to the fabrication method.We summarize the advantages and disadvantages of TENGs with different dimensions.Considering the intrinsically limited conductivity of the fiber and fabric,progress in improving the comprehensive output performance of TENGs via combination with other conductive materials and surface modification is discussed.Finally,this review concludes with a discussion of the challenges,opportunities,and potential applications related to TENGs based on fabric geometric structures.This study is expected to provide readers with new strategies and conceptual ideas to improve the performance of TENGs constructed with fabrics,particularly through the optimization of their structures.

Degraded creep resistance induced by static precipitation strengthening in high-pressure die casting Mg-Al-Sm alloy

Relationship between precipitation strengthening and creep resistance improvement has been an impor-tant topic for the widespread applications of magnesium alloys.Generally,static precipitation strength-ening through thermal stable precipitates would generate satisfactory creep resistance.However,an op-posite example is presented in this work and we propose that the size of precipitates plays a crucial role in controlling the operative creep mechanisms.In addition,the precipitate components along with their crystal structures in the crept Mg-4Al-3Sm-0.4Mn samples with/without pre-aging were thor-oughly studied using Cs aberration-corrected high-angle annular dark-field scanning transmission elec-tron microscopy(HAADF-STEM).Previous aging generates a large density of fine precipitates(<~5 nm)homogeneously distributing in Mg matrix and exhibiting satisfactory strengthening effect.However,the number density of precipitate strings consisting of several or even dozens of relatively coarse precipitates(~10 nm)was significantly decreased at the same time.As revealed in this work,the relatively coarse particles in Mg matrix are much more efficient than the fine precipitates in promoting dislocation climb.Therefore,the rate-controlling mechanisms are transferred from dislocation climb to dislocation slip after previous aging,thus leading to degradation of creep resistance.Moreover,there are mainly five types of precipitates/clusters,namelyβ"-(Al,Mg)3Sm,Al5Sm3,ordered Al-Sm cluster,ordered Al-Mn cluster and ordered/unordered AlMnSm clusters.The crystal structures of the former two precipitates were discussed and the formation mechanisms of the precipitates/clusters were revealed.

Lath-like phases formed at an extremely high temperature in a Mg-RE(RE=rare earth)-Al alloy

Thermal stable intermetallic particles are important for the heat resistance of magnesium(Mg)alloys.In this work,many lath-like particles formed in α-Mg grains of a Mg-8Gd-3Sm-0.7Al casting alloy when heat-treated at 873 K.Atomic-resolution high-angle annular dark field scanning transmission electron microscopy(HAADF-STEM) characterizations indicate that most of them are Mg-containing Al_(2)(Gd,Sm),with the atomic ratio of Mg:Al:(Gd,Sm) being ~1:1:1;a small part of them with relatively wider thickness are long-period stacking ordered(LPSO) phases simultaneously containing both 14H and 18R structures.Both followed common orientation relationships with Mg matrix as those reported in previous work.In addition,many Mg laths were observed in the primary blocky Al_(2)(Gd,Sm) phase at grain boundaries,where the atomic ratio of Al:(Gd,Sm) in the Al_(2)(Gd,Sm) matrix was 2:1.Finally,density functional theory(DFT) calculations illustrated the detail structure of the re-constructed Mg/Al_(2)RE interface and simultaneously deduced the underlying reason for the re-dissolution of the newly formed Mg-containing Al_(2)(Gd,Sm) plates in α-Mg matrix.

Mulberry leaf supplementation inhibits skatole deposition by regulating gut microbiota and upregulating liver cytochrome P4501A1 expression in finishing pigs

Skatole,a strong fecal odor substance,is generated through microbial degradation of tryptophan in the animal hindgut.It easily accumulates in adipose tissue and affects meat quality.In this study,the effect of mulberry leaf supplementation on skatole in finishing pigs was studied.In a 35-day trial,20 finishing pigs(barrows and gilts)were fed with a basal diet or basal diet with 6%mulberry leaves.Growth performance of the pigs(n=10)was automatically recorded by a performance-testing feeder system and 8 pigs in each treatment were slaughtered and sampled for the remaining tests.Skatole and short-chain fatty acids were detected using HPLC and gas chromatography,respectively.Fecal microbiota were analyzed using 16S r RNA gene sequencing.The metabolomics analysis of feces and serum was performed with UHPLC-MS/MS.The major cytochrome P450(CYP)enzymes that catalyze skatole degradation in the liver were tested by using RT-PCR and Western blot.Effects of major bioactive compounds in mulberry leaves on the CYP genes were verified in the hepatic cell line Hep G2 in an in vitro test(n=3).In finishing pigs,mulberry leaf supplementation had no significant effect on the average daily gain,average daily feed intake,and feed conversion ratio(P>0.05),but reduced skatole levels in feces,serum,and backfat(P<0.05),and increased acetic acid levels in feces(P=0.027).Mulberry leaf supplementation decreased the relative abundance of the skatole-producing bacteria Megasphaera and Olsenella(P<0.05).Indole-3acetic acid,the intermediate that is essential for skatole production,was significantly reduced in feces by mulberry leaf supplementation(P<0.05)and was positively correlated with skatole content in feces(P=0.004).In pigs treated with mulberry leaves,liver CYP1A1 expression was increased(P<0.05)and was negatively correlated with skatole content in backfat(P=0.045).The in vitro test demonstrated that mulberry leaf polyphenols and polysaccharides could directly stimulate CYP1A1 expression in hepatic cells.These findings suggest that mulberry leaf supplementation reduces skatole production and deposition in finishing pigs by regulating the gut microbiota and promoting skatole degradation in liver.

Plasmacytoid dendritic cells promote acute kidney injury by producing interferon-α

Acute kidney injury(AKI)is a common clinical complication associated with high mortality in patients.Immune cells and cytokines have recently been described to play essential roles in AKI pathogenesis.Plasmacytoid dendritic cells(pDCs)are a unique DC subset that specializes in type Ⅰ interferon(IFN)production.Here,we showed that pDCs rapidly infiltrated the kidney in response to AKI and contributed to kidney damage by producing IFN-α.Deletion of pDCs using DTR^(BDCA2) transgenic(Tg)mice suppressed cisplatin-induced AKI,accompanied by marked reductions in proinflammatory cytokine production,immune cell infiltration and apoptosis in the kidney.In contrast,adoptive transfer of pDCs during AKI exacerbated kidney damage.We further identified IFN-α as the key factor that mediated the functions of pDCs during AKI,as IFN-α neutralization significantly attenuated kidney injury.Furthermore,IFN-α produced by pDCs directly induced the apoptosis of renal tubular epithelial cells(TECs)in vitro.In addition,our data demonstrated that apoptotic TECs induced the activation of pDCs,which was inhibited in the presence of an apoptosis inhibitor.Furthermore,similar deleterious effects of pDCs were observed in an ischemia reperfusion(IR)-induced AKI model.Clinically,increased expression of IFN-α in kidney biopsies was observed in kidney transplants with AKI.Taken together,the results of our study reveal that pDCs play a detrimental role in AKI via IFN-α.

A facile and general method for synthesis of antibiotic-free protein-based hydrogel:Wound dressing for the eradication of drug-resistant bacteria and biofilms

Antibacterial protein hydrogels are receiving increasing attention in the aspect of bacteria-infected-wound healing. However, bacterial drug resistance and biofilm infections lead to hard healing of wounds, thus the construction of biological agents that can overcome these issues is essential. Here, a simple and universal method to construct antibiotic-free protein hydrogel with excellent biocompatibility and superior antibacterial activity against drug-resistant bacteria and biofilms was developed. The green industrial microbicide tetrakis (hydroxymethyl) phosphonium sulfate (THPS) as cross-linking agent can be quickly cross-linked with model protein bovine serum albumin (BSA) to form antibacterial hydrogel through simple mixing without any other initiators, subsequently promoting drug-resistance bacteria-infected wound healing. This simple gelatinization strategy allows at least ten different proteins to form hydrogels (e.g. BSA, human serum albumin (HSA), egg albumin, chymotrypsin, trypsin, lysozyme, transferrin, myohemoglobin, hemoglobin, and phycocyanin) under the same conditions, showing prominent universality. Furthermore, drug-resistance bacteria and biofilm could be efficiently destroyed by the representative BSA hydrogel (B-Hydrogel) with antibacterial activity, overcoming biofilm-induced bacterial resistance. The in vivo study demonstrated that the B-Hydrogel as wound dressing can promote reepithelization to accelerate the healing of methicillin-resistant staphylococcus aureus (MRSA)-infected skin wounds without inducing significant side-effect. This readily accessible antibiotic-free protein-based hydrogel not only opens an avenue to provide a facile, feasible and general gelation strategy, but also exhibits promising application in hospital and community MRSA disinfection and treatment.