Targeting BCL9/BCL9L enhances antigen presentation by promoting conventional type 1 dendritic cell(cDC1)activation and tumor infiltration

Conventional type 1 dendritic cells(cDC1)are the essential antigen-presenting DC subset in antitumor immunity.Suppressing B-cell lymphoma 9 and B-cell lymphoma 9-like(BCL9/BCL9L)inhibits tumor growth and boosts immune responses against cancer.However,whether oncogenic BCL9/BCL9L impairs antigen presentation in tumors is still not completely understood.Here,we show that targeting BCL9/BCL9L enhanced antigen presentation by stimulating cDC1 activation and infiltration into tumor.Pharmacological inhibition of BCL9/BCL9L with a novel inhibitor hsBCL9z96 or Bcl9/Bcl9l knockout mice markedly delayed tumor growth and promoted antitumor CD8^(+)T cell responses.Mechanistically,targeting BCL9/BCL9L promoted antigen presentation in tumors.This is due to the increase of cDC1 activation and tumor infiltration by the XCL1-XCR1 axis.Importantly,using single-cell transcriptomics analysis,we found that Bcl9/Bcl9l deficient cDC1 were superior to wild-type(WT)cDC1 at activation and antigen presentation via NF-κB/IRF1 signaling.Together,we demonstrate that targeting BCL9/BCL9L plays a crucial role in cDC1-modulated antigen presentation of tumor-derived antigens,as well as CD8^(+)T cell activation and tumor infiltration.Targeting BCL9/BCL9L to regulate cDC1 function and directly orchestrate a positive feedback loop necessary for optimal antitumor immunity could serve as a potential strategy to counter immune suppression and enhance cancer immunotherapy.

The role of gut microbiota and its metabolites short-chain fatty acids in food allergy

Emerging evidence indicated that the increase in food allergy(FA)over the past few decades was associated with the abnormal compositional and metabolic changes of gut microbiota.Gut microbiota played a vital role in maintaining the homeostasis of the immune system and the dysbiosis of gut microbiota promoted the occurrence of FA.Recent research suggested that short-chain fatty acids(SCFAs),the main metabolites derived from gut microbiota,contributed to FA protection.Herein,we provided a comprehensive review on the relationship between gut microbiota and FA.The multifaceted mechanisms underlymg beneficial effects of gut microbiota composition/metabolites on the regulation of diverse cellular pathways in intestinal epithelial cells,dendritic cells,innate lymphoid cells,T cells,B cells and mast cells in the immune system were discussed systematically.These findings emphasized the positive function of gut microbiota in FA and provided novel ideas for the treatment or prevention of FA in the future.

The role of probiotics in prevention and treatment of food allergy

With the prevalence of food allergy increasing every year,food allergy has become a common public health problem.More and more studies have shown that probiotics can intervene in food allergy based on the intestinal mucosal immune system.Probiotics and their metabolites can interact with immune cells and gut microbiota to alleviate food allergy.This review outlines the relationship between the intestinal mucosal immune system and food allergy.This review also presents the clinical application and potential immunomodulation mechanisms of probiotics on food allergy.We aim at providing a reference for further studies to explore the key active substances and immunomodulation mechanisms of anti-allergic probiotics.

Corresponding Prime Number Distribution Equation

The conjecture of twin prime numbers is a mathematical problem. Proving the twin prime conjecture using traditional modern number theory is extremely profound and complex. We propose an elementary research method for corresponding prime number, proved that the conjecture of twin prime numbers and obtain the corresponding prime distribution equation. According to the distribution rate of corresponding prime numbers, the distribution pattern of twin prime numbers was proved the distribution rate theorem. This is the distribution rate of prime numbers corresponding to composite numbers, which approaches the distribution rate of prime numbers corresponding to integers. Based on the corresponding prime distribution equation, obtain the twin prime inequality function. Then, the formula for calculating twin prime numbers was discussed. There is also the Hardy Littlewood conjecture. This provides a practical and feasible approach for studying the distribution of twin prime numbers.

Changes in wheat protein digestibility and allergenicity: role of Pediococcus acidilactici XZ31 and yeast during dough fermentation

Wheat flour,as the most important source of food globally,is one of the most common causative agents of food allergy.This study aimed to investigate the effects of fermentation on wheat protein digestibility and allergenicity.Protein digestibility were evaluated using the sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis and enzyme-linked immunosorbent assay.The effect of protein on intestinal permeability was investigated by Caco-2 cell monolayers.Co-culture fermentation with Pediococcus acidilactici XZ31 and yeast leads to improvement in digestibility of wheat protein compared to single strain fermentation.Fermentation leads to a decrease in albumin/globulin antigenicity and an increase in gluten R5 reactivity,with the most significant changes in the co-culture group.Digestion strengthen the decrease of protein antigenicity and counteracts the difference in antigenicity induced by fermentation between groups.However,pretreatment with P.acidilactici XZ31 reduces the amount of allergens across Caco-2 monolayer and attenuates the gluten-induced increase in permeability of Caco-2 cell monolayer by reducing actin polymerization and villous atrophy.Co-culture fermentation reduces gluten-induced cell monolayer damage to a greater extent than P.acidilactici XZ31 monoculture.These results gives valuable insight into the effects of P.acidilactici XZ31 fermentation on the allergenicity and toxicity of wheat proteins,which contribute to promoting the application of multi-strain leavening agent in hypoallergenic and gluten-free wheat products.

Assessment of immune responses and intestinal flora in BALB/c mice model of wheat food allergy via different sensitization methods

Increasing incidences showed that food allergies have attracted more and more attention from researchers.BALB/c mice were sensitized with wheat gluten combined with aluminum hydroxide adjuvant via intraperitoneal injection,transdermal sensitization,and oral gavage sensitization route.Results showed that all the three sensitization methods could induce allergic symptoms;increase the serum antibody(total immunoglobulin E(IgE),specific IgE,IgG,IgA)and histamine content;promote the secretion of Th2 cytokines(interleukin(IL)-4,IL-5,IL-13)and inflammatory factors(IL-6,IL-17 A,IL-10);and inhibit the production of Th1 cytokines(IFN-γ,IL-2).However,the allergic symptoms of mice sensitized by intraperitoneal injection were the most obvious among the three models.The level of serum antibodies in intraperitoneal injection group was significantly higher than control.Subsequently,16 S rRNA sequencing technology was used to analyze the intestinal flora of mice.The results showed that the abundance of Firmicutes in the wheat protein sensitized group was lower than that in the normal group,while the abundance of Bacteroidetes was higher,and Lactobacillus was the difference marker in normal group.Bacterial species diversity analysis showed that the species richness and diversity of intestinal flora in mice were decreased,the difference between mice induced by intraperitoneal injection and normal control group mice was the most significant.Taken together,these results show that among three sensitization methods used to build a mouse model with aluminum hydroxide as adjuvant,intraperitoneal injection is the comparably best way to build a mouse sensitization mode.

即刻和延期牙龈诱导对上颌前牙种植美学区牙龈高度影响

目的对即刻和延期牙龈诱导对前牙种植美学区牙龈高度的影响差异性进行探究。方法随机抽取我院进行前牙龈诱导修复的160例患者进行回顾分析。随机抽取即刻牙龈诱导修复的观察组与行延期牙龈诱导修复的对照组,对比两组前牙种植美学区牙龈高度差异。结果不同方法治疗后,观察组前牙种植美学区牙龈高度、牙种植区美学明显优于对照组,P<0.05。结论较之延期牙龈诱导修复,即刻牙龈诱导患者其前牙种植美学区牙龈更高,临床效果更佳。

镍钛器械在不同旋转模式下对根尖推出碎屑的体外对比研究

目的:比较ProTaper Universal和Twist File Adaptive两种机用镍钛锉分别在连续旋转和自适应运动模式下行根管预备后推出根尖孔的牙本质碎屑重量。方法:将收集的60颗离体下颌前磨牙随机分为4组(n=15):用ProTaper Universal和Twist File Adaptive两种镍钛锉分别在连续旋转和自适应运动模式下行根管预备至#25,预备过程中每个根管用等量的0.5%次氯酸钠溶液冲洗,用预先称重的试管收集从根尖孔推出的液体及碎屑,测量干燥后推出根尖孔的碎屑重量。结果:ProTaper Universal在两种不同旋转模式组产生的根尖推出物重量均高于Twist File Adaptive组,差异有统计学意义(p<0.05)。相同器械在不同旋转模式下产生的根尖推出物重量之间无显著差异(p>0.05)。结论:不同的器械(ProTaper Universal或Twist File Adaptive)在不同的旋转方式(连续旋转或自适应运动)下预备根管时均可产生根尖推出物。ProTaper Universal镍钛锉在根管预备中根尖孔的碎屑推出量比Twist File Adaptive镍钛锉多。

Advances in research on earthquake fluids hydrogeology in China:a review

Monitoring of subsurface fluid （underground fluid） is an important part of efforts for earthquake prediction in China. The nationwide network, which monitors groundwater level, water temperature, and radon and mercury in groundwater, has been constructed in the last decades. Large amounts of abnormal fluid changes before and after major earthquakes have been recorded, providing precious data for research in earthquake sciences. Many studies have been done in earthquake fluid hydrogeology in order to probe the nature of the earthquake. Much progress in earthquake fluid hydrogeology has been made in the last decades. The paper provides a review of the advances in research on earthquake fluid hydrogeology over the last 40 years in China. It deals with the following five aspects： （1） an introduction to the development history of monitoring networks construction; （2） cases of different subsurface fluid changes recorded before some major earthquakes which occurred in the last decades; （3） characteristics of subsurface fluid changes following major earthquakes; （4） mechanism of subsurface fluid changes before and following earthquakes; （5） application of earthquake fluids in the hydrogeology field.

Low-depth whole genome sequencing reveals copy number variations associated with higher pathologic grading and more aggressive subtypes of lung non-mucinous adenocarcinoma

Objective:Histology grade,subtypes and TNM stage of lung adenocarcinomas are useful predictors of prognosis and survival.The aim of the study was to investigate the relationship between chromosomal instability,morphological subtypes and the grading system used in lung non-mucinous adenocarcinoma(LNMA).Methods:We developed a whole genome copy number variation(WGCNV)scoring system and applied next generation sequencing to evaluate CNVs present in 91 LNMA tumor samples.Results:Higher histological grades,aggressive subtypes and more advanced TNM staging were associated with an increased WGCNV score,particularly in CNV regions enriched for tumor suppressor genes and oncogenes.In addition,we demonstrate that 24-chromosome CNV profiling can be performed reliably from specific cell types(<100 cells)isolated by sample laser capture microdissection.Conclusions:Our findings suggest that the WGCNV scoring system we developed may have potential value as an adjunct test for predicting the prognosis of patients diagnosed with LNMA.

Possible precursory anomalies in ground water level associated with the Wenchuan Ms 8.0 earthquake in 2008,Sichuan,China

We have examined the water level data from 16 wells in Sichuan province,China,recorded before the Wenchuan Ms8.0 earthquake occurred in 2008.We found that the data of 5 among these wells exhibit possible precursory anomalies,which are respectively named the Chuan No.08 well in Deyang,Chuan No.ll well in Pujiang,Chuan No.13 well in Luzhou,Chuan No.22 well in Qionglai and Beichuan.In time durations,these anomalies are of long-,intermediate-and short-term signals which are primarily distributed on the northeast(NE)trending Longmenshan fault zone as well as the parallel Huayingshan fault zone.It seems that the variations of the well levels on the Huayingshan fault zone imply compression while those on the Longmenshan fault zone reflect extension.These anomalies occurred first in the areas outside the epicenter region of the Wenchuan Ms8.0 earthquake,then migrated to the seismogenic fault zone.And they migrated from southwest to northeast in agreement with the rupture process of the main shock.

Coseismic responses of groundwater levels in the Three Gorges well-network to the Wenchuan M_S8.0 earthquake

We systematically analyze coseismic responses and post-seismic characteristics of groundwater levels in the Three Gorges well-network to the Ms8.0 Wenchuan earthquake on 12 May 2008. The results indicate that these characteristics differ among wells. On the conditions of similar borehole configurations, the differences are associated with geological structural sites of wells, burial types of aquifers monitored, and transmissivities of aquifer systems. We explored coseismic and post-seismic step-rise and step-drop mechanical mechanisms and their implication to earthquake prediction. We validated the inference that the residual step-rise zone is a possible earthquake risk zone based on recent seismic activity on the Xiannüshan fault in the area.

Turning depths of internal tides in the South China Sea inferred from profile data

Theoretically,propagating internal tides in the ocean may reflect at turning depths,where buoyancy frequencies equal tidal frequencies,before colliding with the air-sea interface or rugged bottom topography.Globally,the internal tide lower turning depths(ITLTDs)in the open ocean have been mapped;however,knowledge of the presence of ITLTDs in the South China Sea(SCS)is lacking.In this study,2125 high-quality temperature-salinity profiles(including 58 deep-sea hydrographic measurements with observational depths exceeding 3000 m)are collected and analyzed to investigate the existence of ITLTDs in the SCS.Furthermore,the concept of the upper turning depth is first introduced in the context of internal tides,and internal tide upper turning depths(ITUTDs)are also investigated.ITLTDs are found to exist at several abyssal stations;these stations are distributed mostly in the southern part of the SCS basin,possibly due to the greater water depths there.Fewer locations show the presence of ITLTDs for K_(1) versus M_(2) tidal frequencies because of the lower tidal frequency.The distance between ITLTDs and the seafloor ranged from 270 m to more than 1200 m,implying the possible existence of multiple internal wave evanescent regions in the abyssal bottom.ITUTDs of tens of meters are ubiquitous in the SCS;stations with the presence of ITUTDs are located mainly in the northeastern SCS due to the intensive observations there.However,the calculated ITUTDs have large uncertainties;they are sensitive to the selected bin values.The horizontal propagation directions of internal tides in the SCS change dramatically,and as a result,the estimated turning depths under the full Coriolis force definition are different compared to that under the traditional approximation.

Differentiated self-assembly through orthogonal noncovalent interactions towards the synthesis of two-dimensional woven supramolecular polymers

Molecular weaving is a powerful approach to make molecularly woven materials that have showed unprecedented characteristics and properties intrinsically distinct to those of non-woven materials.We here report a facile and efficient approach for the synthesis of 2D woven supramolecular polymers by differentiated self-assembly through orthogonal noncovalent interactions.Importantly,the difference in binding strength of two orthogonal noncovalent interactions can be used to control the process of molecular weaving.Consequently,single-layered 2D woven supramolecular polymers were synthesized and fully characterized by various techniques.This study demonstrates a controllable method for molecular weaving,and will significantly hasten the development of molecularly woven materials.

Laser pattern-induced unidirectional lubricant flow for lubrication track replenishment

Effective oil replenishment to the lubrication track of a running bearing is crucial to its sustainable operation.Reliable practical solutions are rare despite numerous theoretical studies were conducted in the last few decades.This paper proposes the use of surface effect,wettability gradient,to achieve the goal.This method is simple and can be nicely implemented using femtosecond laser ablation.A periodic comb-tooth-shaped pattern with anisotropic wetting capability is devised and its effect on the anisotropic spreading behaviour of an oil droplet is studied.Results show that the comb-tooth-shaped pattern enables the rearrangement of oil distribution,thereby escalating oil replenishment to the lubrication track.The effect is due to the unbalanced interfacial force created by the surface pattern.The influence of the shape and the pitch of teeth,which are the two governing factors,on oil transport is also reported.The effects of the newly devised surface pattern on lubrication are experimentally evaluated under the conditions of limited lubricant supply.These results are promising,demonstrating the reduction in bearing friction and the increase in lubricating film thickness.

超结构α-Fe2O3纳米棒作为新型无黏结剂阳极用于高性能纤维状镍/铁电池

本文首先通过溶剂热法在导电碳纳米管纤维上合成超结构α-Fe2O3纳米棒,随后在其表面包覆了一层PPy,从而获得负极材料,并用于组装了高性能全固态纤维状镍铁电池.该工作的突出亮点在于超结构3D α-Fe2O3纳米棒具有丰富的空位和通道,有效地缩短了离子传输的距离;此外,丰富的通道使离子易于与内部活性物质反应,从而改善了电化学性能,因此合成的α-Fe2O3电极材料具有高的比容量和优异的倍率性能.总的来说,本文在导电CNTF上合成具有高电化学性能的超结构α-Fe2O3@PPy核壳纳米棒电极材料.独特的超结构α-Fe2O3@PPy纳米棒由于其较大的比表面积和较高的电导率而显著改善了电化学性能;高导电性的PPy壳层亦明显增强了电子和离子的扩散.该工作有助于高能量密度水系可穿戴式电池的发展,为未来便携式和可穿戴电子产品提供动力.

Boosting Zn-ion storage capability of self-standing Zn-doped Co_(3)O_(4)nanowire array as advanced cathodes for high-performance wearable aqueous rechargeable Co//Zn batteries

Neutral aqueous rechargeable Co_(3)O_(4)//Zn batteries with high-output voltage and outstanding cycling stability have yielded new insights into wearable energy-storage devices.To meet the increasing demand for a means of powering wearable and portable devices,the development of a high-performance fiber-shaped Co//Zn battery would be highly desirable.However,the intrinsically poor conductivity of C 03O4 significantly restricts the application of these high-capacity and high-rate aqueous rechargeable battery.Encouragingly,density functional theory(DFT)calculations demonstrate that the substitution of Zn for Co^(3+)leads to an insulatormetal transition in the Zn-doped Co_(3)O_(4)(Zn-Co_(3)O_(4)).In this study,we used metallic Zn-Co_(3)O_(4)nanowire arrays(NWAs)as a novel binder-free cathode to successfully fabricate an all-solid-state fiber-shaped aqueous rechargeable(AFAR)Co//Zn battery.The resulting fiber-shaped Co//Zn battery takes advantage of the enhanced conductivity,increased capacity,and improved rate capability of Zn-Co_(3)O_(4)NWAs to yield a remarkable capacity of 1.25 mAh·cm^(-2)at a current density of 0.5 mA·cm^(-2),extraordinary rate capability(60.8%capacity retention at a high current density of 20 mA·cm^(-2))and an admirable energy density of 772.6 mWh·cm^(-3).Thus,the successful construction of Zn-Co_(3)O_(4)NWAs provides valuable insights into the design of high-capacity and high-rate cathode materials for aqueous rechargeable high-voltage batteries.

BCL9 regulates CD226 and CD96 checkpoints in CD8^(+)T cells to improve PD-1 response in cancer

To date,the overall response rate of PD-1 blockade remains unsatisfactory,partially due to limited understanding of tumor immune microenvironment(TIME).B-cell lymphoma 9(BCL9),a key transcription co-activator of the Wnt pathway,is highly expressed in cancers.By genetic depletion and pharmacological inhibition of BCL9 in tumors,we found that BCL9 suppression reduced tumor growth.

Heat-treatable Mg-9Al-6Sn-3Zn extrusion alloy

Mg-9Al-6Sn-3Zn （wt%） alloy was extruded and heat treated in T5 and T6 conditions, and its mechanical properties and microstructures were investigated. The extruded product can be slightly strengthened by the T5 treatment as a result of sparse and heterogeneous precipitation. Significant increase in strength is achieved by the T6 treatment, and this is mostly attributed to the formation of lamellar discontinuous Mg17Al12 precipitates. The segregation of Al and Zn at grain boundaries is responsible for the discontinuous Mg17Al12 nucleation. The T6-treated alloy exhibits a tensile yield strength of 341 MPa and an ultimate tensile strength of 409 MPa, together with an elongation to fracture of 4%.