Computed tomography imaging features for amyloid dacryolith in the nasolacrimal excretory system:A case report

BACKGROUND Nasolacrimal duct obstruction leading to epiphora is a common ophthalmologic complaint,and it may derive from amyloidosis in rare cases.There are a few reports about localized amyloidosis,and amyloidosis with involvement and obstruction of the nasolacrimal duct is exceedingly rare.CASE SUMMARY A 54-year-old male presented with a 2-year history of a lump overlying the left lacrimal sac that had grown rapidly for nearly half a year.Physical examination touched a firm lump in the left lacrimal sac.Nasal endoscopy discovered lesions in appearance of sediments with easy bleeding at the entry of the nasolacrimal duct of the left inferior nasal meatus.Computerized tomography scan revealed speckle high density in the left lacrimal sac and the dilated nasolacrimal duct.During an endoscopic exploration and excision,a large number of dacryoliths were exposed.Pathology indicated amorphous pink material and multinucleated giant cell reaction in the fibrous tissue.CONCLUSION This case showed amyloidosis in localized form mimicking dacryolith with nasolacrimal duct obstruction.In clinical practice,we should be aware of the possibility of localized amyloidosis in the nasolacrimal excretory system.

The lncRNA Snhgl-Vpsl3D vesicle trafficking system promotes memory CD8 T cell establishment via regulating the dual effects of IL-7 signaling

The efficient induction and long-term persistence of pathogen-specific memory CD8 T cells are pivotal to rapidly curb the reinfection.Recent studies indicated that long-noncoding RNAs expression is highly cell-and stage-specific during T cell development and differentiation,suggesting their potential roles in T cell programs.However,the key lncRNAs playing crucial roles in memory CD8 T cell establishment remain to be clarified.Through CD8 T cell subsets profiling of lncRNAs,this study found a key lncRNA-Snhgl with the conserved naivehl-effectorlo-memoryh,expression pattern in CD8 T cells of both mice and human,that can promote memory formation while impeding effector CD8 in acute viral infection.Further,Snhgl was found interacting with the conserved vesicle trafficking protein Vps13D to promote IL-7Ra membrane location specifically.With the deep mechanism probing,the results show Snhgl-Vps13D regulated IL-7 signaling with its dual effects in memory CD8 generation,which not just because of the sustaining role of STAT5-BCL-2 axis for memory survival,but more through the STAT3-TCF1-Blimp1 axis for transcriptional launch program of memory differentiation.Moreover,we performed further study with finding a similar high-low-high expression pattern of human SNHG1A/PS13D/IL7R/TCF7 in CD8 T cell subsets from PBMC samples of the convalescent COVID-19 patients.The central role of Snhgl-Vps13D-IL-7R-TCF1 axis in memory CD8 establishment makes it a potential target for improving the vaccination effects to control the ongoing pandemic.

Low level of ARID1A contributes to adaptive immune resistance and sensitizes triple-negative breast cancer to immune checkpoint inhibitors

Background Immune checkpoint inhibitors(ICIs)shed new light on triple-negative breast cancer(TNBC),but only a minority of patients demonstrate response.Therefore,adaptive immune resistance(AIR)needs to be further defined to guide the development of ICI regimens.Methods Databases,including The Cancer Genome Atlas,Gene Ontology Resource,University of California Santa Cruz Genome Browser,and Pubmed,were used to screen epigenetic modulators,regulators for CD8+T cells,and transcriptional regulators of programmed cell death-ligand 1(PD-L1).Human peripheral blood mononuclear cell(Hu-PBMC)reconstruction mice were adopted for xenograft transplantation.Tumor specimens from a TNBC cohort and the clinical trial CTR20191353 were retrospectively analyzed.RNA-sequencing,Western blotting,qPCR and immunohistochemistry were used to assess gene expression.Coculture assays were performed to evaluate the regulation of TNBC cells on T cells.Chromatin immunoprecipitation and transposase-accessible chromatin sequencing were used to determine chromatin-binding and accessibility.Results The epigenetic modulator AT-rich interaction domain 1A(ARID1A)gene demonstrated the highest expression association with AIR relative to other epigenetic modulators in TNBC patients.Low ARID1A expression in TNBC,causing an immunosuppressive microenvironment,promoted AIR and inhibited CD8+T cell infiltration and activity through upregulating PD-L1.However,ARID1A did not directly regulate PD-L1 expression.We found that ARID1A directly bound the promoter of nucleophosmin 1(NPM1)and that low ARID1A expression increased NPM1 chromatin accessibility as well as gene expression,further activating PD-L1 transcription.In Hu-PBMC mice,atezolizumab demonstrated the potential to reverse ARID1A deficiency-induced AIR in TNBC by reducing tumor malignancy and activating anti-tumor immunity.In CTR20191353,ARID1A-low patients derived more benefit from pucotenlimab compared to ARID1A-high patients.Conclusions In AIR epigenetics,low ARID1A expression in TNBC contributed to AIR via the ARID1A/NPM1/PD-L1 axis,leading to poor outcome but sensitivity to ICI treatment.

An intriguing RNA species--perspectives of circularized RNA

圆形的 RNA (circRNAs ) ，一种 covalently 关上的 RNA 分子，被认为拼接 mis 事件的副产品的一种类型并且在早年里由于工艺的限制偶发地被发现。与象高产量的下一代的定序那样的大工艺的进步，众多的 circRNAs 最近在许多种类被检测了。CircRNAs 以一种时间空间地特定的方式被表示，建议他们的规章的功能的潜力以前被俯看。有趣地，某 circRNAs 确实在某些情形与批评生理的功能被发现。CircRNAs 有能抵抗到比作那些线性的 exoribonuclease 的更稳定的分子的结构，并且他们的分子的函数包括 microRNA 海绵，在抄写的规章的角色，与线性拼接竞争的 mRNA 陷井，为翻译并且可能的模板另外的一会儿未知的角色。这里，我们考察 circRNAs，起源和形成机制，生理的功能和分子的角色的发现和描述，与为 circRNAs 的察觉的方法一起。我们进一步调查未来并且建议关键问题为这些魔术的 RNA 分子被回答。

SMYD3-PARP16 axis accelerates unfolded protein response and mediates neointima formation

Neointimal hyperplasia after vascular injury is a representative complication of restenosis.Endoplasmic reticulum(ER)stress-induced unfolded protein response(UPR)is involved in the pathogenesis of vascular intimal hyperplasia.PARP16,a member of the poly(ADP-ribose)polymerases family,is correlated with the nuclear envelope and the ER.Here,we found that PERK and IRE1 a are ADPribosylated by PARP16,and this might promote proliferation and migration of smooth muscle cells(SMCs)during the platelet-derived growth factor(PDGF)-BB stimulating.Using chromatin immunoprecipitation coupled with deep sequencing(ChIP-seq)analysis,PARP16 was identified as a novel target gene for histone H3 lysine 4(H3 K4)methyltransferase SMYD3,and SMYD3 could bind to the promoter of Parp16 and increased H3 K4 me3 level to activate its host gene’s transcription,which causes UPR activation and SMC proliferation.Moreover,knockdown either of PARP16 or SMYD3 impeded the ER stress and SMC proliferation.On the contrary,overexpression of PARP16 induced ER stress and SMC proliferation and migration.In vivo depletion of PARP16 attenuated injury-induced neointimal hyperplasia by mediating UPR activation and neointimal SMC proliferation.This study identified SMYD3-PARP16 is a novel signal axis in regulating UPR and neointimal hyperplasia,and targeting this axis has implications in preventing neointimal hyperplasia related diseases.

Alternative Polyadenylation： Methods, Findings, and Impacts

Alternative polyadenylation(APA), a phenomenon that RNA molecules with different 30 ends originate from distinct polyadenylation sites of a single gene, is emerging as a mechanism widely used to regulate gene expression. In the present review, we first summarized various methods prevalently adopted in APA study, mainly focused on the next-generation sequencing(NGS)-based techniques specially designed for APA identification, the related bioinformatics methods, and the strategies for APA study in single cells. Then we summarized the main findings and advances so far based on these methods, including the preferences of alternative poly A(pA) site, the biological processes involved, and the corresponding consequences. We especially categorized the APA changes discovered so far and discussed their potential functions under given conditions, along with the possible underlying molecular mechanisms. With more in-depth studies on extensive samples,more signatures and functions of APA will be revealed, and its diverse roles will gradually heave in sight.

Metastasis-related methyltransferase 1(Merml)represses the methyltransferase activity of Dnmt3a and facilitates RNA polymerase I transcriptional elongation

Stimulatory regulators for DNA methyltransferase activity,such as Dnmt3L and some Dnmt3b isoforms,affect DNA methylation patterns,thereby maintaining gene body methylation and maternal methylation imprinting,as well as the methylation landscape of pluripotent cells.Here we show that metastasis-related methyltransferase 1(Merm1),a protein deleted in individuals with Williams-Beuren syndrome,acts as a repressive regulator of Dnmt3a.Merm1 interacts with Dnmt3a and represses its methyltransferase activity with the requirement of the binding motif for S-adenosyl-L-methionine.Functional analysis of gene regulation revealed that Merm1 is capable of maintaining hypomethylated rRNA gene bodies and co-localizes with RNA polymerase I in the nucleolus.Dnmt3a recruits Merml,and in return,Merml ensures the binding of Dnmt3a to hypomethylated gene bodies.Such interplay between Dnmt3a and Merml facilitates transcriptional elongation by RNA polymerase I.Our findings reveal a repressive factor for Dnmt3a and uncover a molecular mechanism underlying transcriptional elongation of rRNA genes.

Measurement of HONO flux using the aerodynamic gradient method over an agricultural field in the Huaihe River Basin,China

To investigate nitrous acid(HONO)levels and potential HONO sources above crop rotation fields.The HONO fluxes were measured by the aerodynamic gradient(AG)method from 14 December 2019 to 2 January 2020 over an agricultural field in the Huaihe River Basin.The ambient HONO levels were measured at two different heights(0.15 and 1.5 m),showing a typical diurnal cycle with low daytime levels and high nighttime levels.The upward HONO fluxes were mostly observed during the day,whereas deposition dominated at night.The diurnal variation of HONO flux followed solar radiation,with a noontime maximum of 0.2 nmol/(m^(2)·sec).The average upward HONO flux of 0.06±0.17 nmol/(m^(2)·sec)indicated that the agricultural field was a net source for atmospheric HONO.The higher HONO/NO_(2)ratio and NO_(2)-to-HONO conversion rate close to the surface suggested that nocturnal HONO was formed and released near the ground.The unknown HONO source was derived from the daytime HONO budget analysis,with an average strength of 0.31 ppbV/hr at noontime.The surface HONO flux,which was highly correlated with the photolysis frequency J(NO_(2))(R^(2)=0.925)and the product of J(NO_(2))×NO_(2)(R^(2)=0.840),accounted for∼23%of unknown daytime HONO source.The significant correlation between HONO fluxes and J(NO_(2))suggests a light-driven HONO formation mechanism responsible for the surface HONO flux during daytime.