Digital pathology-based artificial intelligence models for differential diagnosis and prognosis of sporadic odontogenic keratocysts

Odontogenic keratocyst(OKC)is a common jaw cyst with a high recurrence rate.OKC combined with basal cell carcinoma as well as skeletal and other developmental abnormalities is thought to be associated with Gorlin syndrome.Moreover,OKC needs to be differentiated from orthokeratinized odontogenic cyst and other jaw cysts.Because of the different prognosis,differential diagnosis of several cysts can contribute to clinical management.We collected 519 cases,comprising a total of 2157 hematoxylin and eosinstained images,to develop digital pathology-based artificial intelligence(AI)models for the diagnosis and prognosis of OKC.The Inception_v3 neural network was utilized to train and test models developed from patch-level images.Finally,whole slide imagelevel AI models were developed by integrating deep learning-generated pathology features with several machine learning algorithms.The AI models showed great performance in the diagnosis(AUC=0.935,95%CI:0.898–0.973)and prognosis(AUC=0.840,95%CI:0.751–0.930)of OKC.The advantages of multiple slides model for integrating of histopathological information are demonstrated through a comparison with the single slide model.Furthermore,the study investigates the correlation between AI features generated by deep learning and pathological findings,highlighting the interpretative potential of AI models in the pathology.Here,we have developed the robust diagnostic and prognostic models for OKC.The AI model that is based on digital pathology shows promise potential for applications in odontogenic diseases of the jaw.

种猪场伪狂犬病的净化策略

猪伪狂犬病是由伪狂犬病毒引起的一种以母猪繁殖障碍和仔猪高死亡率为主要特征的急性、热性高度接触性传染病。2011年以来猪伪狂犬病毒变异株导致了免疫猪群暴发该病,对养猪业造成较大的经济损失。因此,种猪场应抓住严防非洲猪瘟的有利契机,同时做好猪伪狂犬病的净化非常重要。文章简要综述了国内外常用的净化方案、净化措施,为养猪场实施净化提供参考。

Preparation of rabbit anti-rat LRRN3 polyclonal antibody and study of its expression

BACKGROUND： Studies have shown that the Repeat superfamily, could be related to neural LRRN3, a member of the Neuron Leucine-Rich development, differentiation, information transmission, and other functions, but most studies have focused on nucleic acid levels and few have reported on LRRN3 protein levels. OBJECTIVE： To prepare rabbit anti-rat LRRN3 polyclonal antibody and to observe protein tissue expression profiles. DESIGN, TIME AND SEI-rlNG： In vitro, molecular, biological experiments were performed from October 2007 to April 2009 in Laboratory of Neurobiology at Xiangya School of Medicine, Central South University. MATERIALS： Immunization antigen, namely rat MaI-LRRN3C-His recombinant protein, was provided by the Laboratory of Neurobiology at Xiangya School of Medicine, Central South University. METHODS： Rat Mal-LRRN3C-His recombinant protein was used to immunize male, New Zealand rabbits, and rabbit anti-rat LRRN3 polyclonal antibody was prepared. MAIN OUTCOME MEASURES： Antibody purification was conducted using Protein A affinity chromatography, and the LRRN3 anti-serum titer was identified using enzyme-linked immunosorbent assay. Immunohistochemical techniques and Western blot preliminary tests were used to determine LRRN3 protein expression profiles in adult rats. RESULTS： A highly purified rabbit anti-rat LRRN3 polyclonal antibody was obtained. Western Blot results from rat brain total protein revealed a band at 79 kD, which was consistent with the size of LRRN3. Immunohistochemistry results showed that protein was mainly expressed in the central nervous system, and no significant positive signals were observed in other tissues. Positive cells included neurons of cerebral cortex and hippocampal dentate gyrus granule cell layer, and cerebellar Purkinje cells. There was no positive expression in glial cells. CONCLUSION： Rabbit anti-rat LRRN3 polyclonal antibody was successfully prepared at a high purity from the prokaryotic-expressed MaI-LRRN3C-His recombinant protein, which served as an antigen. Rat LRRN3 protein was primarily expressed in cerebral cortex neurons, hippocampal dentate gyrus granule cell layer neurons, and cerebellar Purkinje cells.

MiR-4465-modified mesenchymal stem cell-derived small extracellular vesicles inhibit liver fibrosis development via targeting LOXL2 expression

Liver fibrosis is a significant health burden,marked by the consistent deposition of collagen.Unfortunately,the currently available treatment approaches for this condition are far from optimal.Lysyl oxidase-like protein 2(LOXL2)secreted by hepatic stellate cells(HSCs)is a crucial player in the cross-linking of matrix collagen and is a significant target for treating liver fibrosis.Mesenchymal stem cell-derived small extracellular vesicles(MSC-sEVs)have been proposed as a potential treatment option for chronic liver disorders.Previous studies have found that MSC-sEV can be used for microRNA delivery into target cells or tissues.It is currently unclear whether microRNA-4465(miR-4465)can target LOXL2 and inhibit HSC activation.Additionally,it is uncertain whether MSC-sEV can be utilized as a gene therapy vector to carry miR-4465 and effectively inhibit the progression of liver fibrosis.This study explored the effect of miR-4465-modified MSC-sEV(MSC-sEVmiR-4465)on LOXL2 expression and liver fibrosis development.The results showed that miR-4465 can bind specifically to the promoter of the LOXL2 gene in HSC.Moreover,MSC-sEVmiR-4465 inhibited HSC activation and collagen expression by downregulating LOXL2 expression in vitro.MSC-sEVmiR-4465 injection could reduce HSC activation and collagen deposition in the CCl4-induced mouse model.MSC-sEVmiR-4465 mediating via LOXL2 also hindered the migration and invasion of HepG2 cells.In conclusion,we found that MSC-sEV can deliver miR-4465 into HSC to alleviate liver fibrosis via altering LOXL2,which might provide a promising therapeutic strategy for liver diseases.

Comparison of the capacity of biological desulfurization of Thiobacillus ferrooxidans from different sulfur-containing substrates with or without additional ferrous iron

Thiobacillus ferrooxidans,abbreviated as T.ferrooxidans is one of the important microorganisms in the field of biological desulfurization.Effects of ferrous iron and sulfur-containing substrates on biological desulfurization of T.ferrooxidans were studied.Results show that in the absence of Fe^(2+),T.ferrooxidans can utilize three kinds of sulfur-containing substrates of Na_(2)S_(2)O_(3),elemental S and Na_(2)SO_(3) for growth and metabolism.For utilization complexity,Na_(2)S_(2)O_(3) was easiest to use,next was elemental S,and Na_(2)SO_(3) was the worst for use.During the utilization of ferrous iron and sulfur-containing substrates by T.ferrooxidans,the iron oxidation system was first started.With the decrease of the Fe^(2+)concentration,the sulfur oxidation system was started,and then the two systems synergistically acted.The presence of three sulfur-containing substrates had different effects on Fe^(2+)oxidation,and elemental S did not inhibit the oxidation of Fe^(2+),while Na_(2)S_(2)O_(3) and Na_(2)SO_(3) had some inhibition on the oxidation of Fe^(2+),especially the inhibition of Na_(2)SO_(3) was significant,and complete oxidation of ferrous iron needed more time.The isolated T.ferrooxidans is applied to the removal of H2S gas,aiming to provide a new technological approach for biological removal of H2S.

Emerging phagocytosis checkpoints in cancer immunotherapy

Cancer immunotherapy,mainly including immune checkpoints-targeted therapy and the adoptive transfer of engineered immune cells,has revolutionized the oncology landscape as it utilizes patients’own immune systems in combating the cancer cells.Cancer cells escape immune surveillance by hijacking the corresponding inhibitory pathways via overexpressing checkpoint genes.Phagocytosis checkpoints,such as CD47,CD24,MHC-I,PD-L1,STC-1 and GD2,have emerged as essential checkpoints for cancer immunotherapy by functioning as“don’t eat me”signals or interacting with“eat me”signals to suppress immune responses.Phagocytosis checkpoints link innate immunity and adaptive immunity in cancer immunotherapy.Genetic ablation of these phagocytosis checkpoints,as well as blockade of their signaling pathways,robustly augments phagocytosis and reduces tumor size.Among all phagocytosis checkpoints,CD47 is the most thoroughly studied and has emerged as a rising star among targets for cancer treatment.CD47-targeting antibodies and inhibitors have been investigated in various preclinical and clinical trials.However,anemia and thrombocytopenia appear to be formidable challenges since CD47 is ubiquitously expressed on erythrocytes.Here,we review the reported phagocytosis checkpoints by discussing their mechanisms and functions in cancer immunotherapy,highlight clinical progress in targeting these checkpoints and discuss challenges and potential solutions to smooth the way for combination immunotherapeutic strategies that involve both innate and adaptive immune responses.

Global Well-Posedness of the Inviscid Heat-Conductive Resistive Compressible MHD in a Strip Domain

This paper concerns the inviscid,heat conductive and resistive compressible MHD system in a horizontally periodic flat strip domain.The global well-posedness of the problem around an equilibrium with the positive constant density and temperature and a uniform non-horizontal magnetic field is established,and the solution decays to the equilibrium almost exponentially.Our result reveals the strong stabilizing effect of the transversal magnetic field and resistivity as the global well-posedness of compressible inviscid heat-conductive flows in multi-D is unknown.

PD-L1 regulates genomic stability via interaction with cohesin-SAl in the nucleus

Dear Editor,Programmed death ligand-1(PD-L1)is a type 1 transmembrane protein and highly expressed in various cancers that binds to PD-1 on T cells,inhibits T cell activity and proliferation,facilitates cancer cells to escape T cell-mediated immune surveillance.Immunotherapies by PD-L1/PD-1 blockade have shown effectiveness against different cancer types and revolutionizes cancer treatment in the clinic.However,the response rate to anti-PD-L1/PD-1 antibody remains at about 15-30%as a single agent.1 Thus,there is more to understand regarding the function of PD-L1 in cancer.

Propagation of Density-Oscillations in Solutions to the Compressible Navier-Stokes-Poisson System

Concerning a bounded sequence of finite energy weak solutions to the compressible Navier-Stokes-Poisson system (denoted by CNSP), which converges up to extraction of a subsequence, the limit system may not be the same system. By introducing Young measures as in [6, 15], the authors deduce the system (HCNSP) which the limit functions must satisfy. Then they solve this system in a subclass where Young measures are convex combinations of Dirac measures, to give the information on the propagation of density-oscillations. The results for strong solutions to (CNSP) (see Corollary 6.1) are also obtained.