Search

Long noncoding RNAs (lncRNAs) are emerging as a new class of important regulators of signal transduction in tissue homeostasis and cancer development. Liquid-liquid phase separation (LLPS) occurs in a wide range of biological processes, while its role in signal transduction remains largely undeciphered. In this study, we uncovered a lipid-associated lncRNA, small nucleolar RNA host gene 9 (SNHG9) as a tumor-promoting lncRNA driving liquid droplet formation of Large Tumor Suppressor Kinase 1 (LATS1) and inhibiting the Hippo pathway. Mechanistically, SNHG9 and its associated phosphatidic acids (PA) interact with the C-terminal domain of LATS1, promoting LATS1 phase separation and inhibiting LATS1-mediated YAP phosphorylation. Loss of SNHG9 suppresses xenograft breast tumor growth. Clinically, expression of SNHG9 positively correlates with YAP activity and breast cancer progression. Taken together, our results uncover a novel regulatory role of a tumor-promoting lncRNA (i.e., SNHG9) in signal transduction and cancer development by facilitating the LLPS of a signaling kinase (i.e., LATS1).

Environmental pH influences cell growth and differentiation. In the dimorphic yeast Yarrowia lipolytica, neutral-alkaline pH strongly induces the yeast-to-filament transition. However, the regulatory mechanism that governs alkaline pH-induced filamentation has been unclear. Here, we show that the pH-responsive transcription factor Y. lipolytica Rim101 (YlRim101) is a major regulator of alkaline-induced filamentation, since the deletion of YlRIM101 severely impaired filamentation at alkaline pH, whereas the constitutively active YlRIM1011-330 mutant mildly induced filamentation at acidic pH. YlRim101 controls the expression of the majority of alkaline-regulated cell wall protein genes. One of these, the cell surface glycosidase gene YlPHR1, plays a critical role in growth, cell wall function, and filamentation at alkaline pH. This finding suggests that YlRim101 promotes filamentation at alkaline pH via controlling the expression of these genes. We also show that, in addition to YlRim101, the Msn2/Msn4-like transcription factor Mhy1 is highly upregulated at alkaline pH and is essential for filamentation. However, unlike YlRim101, which specifically regulates alkaline-induced filamentation, Mhy1 regulates both alkaline- and glucose-induced filamentation, since the deletion of MHY1 abolished them both, whereas the overexpression of MHY1 induced strong filamentation irrespective of the pH or the presence of glucose. Finally, we show that YlRim101 and Mhy1 positively coregulate seven cell wall protein genes at alkaline pH, including YlPHR1 and five cell surface adhesin-like genes, three of which appear to promote filamentation. Together, these results reveal a conserved role of YlRim101 and a novel role of Mhy1 in the regulation of alkaline-induced filamentation in Y. lipolytica. IMPORTANCE The regulatory mechanism that governs pH-regulated filamentation is not clear in dimorphic fungi except in Candida albicans. Here, we investigated the regulation of alkaline pH-induced filamentation in Yarrowia lipolytica, a dimorphic yeast distantly related to C. albicans. Our results show that the transcription factor YlRim101 and the Msn2/Msn4-like transcription factor Mhy1 are the major regulators that promote filamentation at alkaline pH. They control the expression of a number of cell wall protein genes important for cell wall organization and filamentation. Our results suggest that the Rim101/PacC homologs play a conserved role in pH-regulated filamentation in dimorphic fungi.

Phosphorus (P) is an important factor driving algal growth in aquatic ecosystems. In the present study, the growth, P uptake and utilization, photosynthesis, and transcriptome profile of Nostoc sp. were measured when Nostoc sp. cultured in media containing β-glycerol phosphate (β-gly, containing COP bonds), 2-aminoethylphosphonic acid (2-amin, containing CP bonds), or orthophosphate (K2HPO4), and in P-free (NP) medium. The results revealed that NP treatment adversely affected the growth and photosynthesis of Nostoc sp. and significantly down-regulated the expression of genes related to nutrient transport and material metabolism. Furthermore, 2-amin treatment reduced the growth of Nostoc sp. but did not significantly reduce photosynthesis, and the treatments of NP and 2-amin up-regulated the expressions of genes related antioxidation and stress. Additionally, there were no obvious differences in growth, photosynthesis, and phosphorus utilization between the β-gly and K2HPO4 treatments. These results suggested that Nostoc had a flexible ability to utilize P, which might play an important role in its widespread distribution in the environment.

A laboratory-scale anaerobic membrane bioreactor (AnMBR) was used for the co-digestion of sewage sludge and food waste to investigate its organic matter removal characteristics, biogas production performance, and microbial community composition. The results showed that the degradation rate of volatile solids (VS) increased from 17.5% for a single digestion to 40% for the total digestion, and that the COD removal was 95.3% when the organic loading rate (OLR) was stabilized at 0.59-0.64 kg·(m

In order to study changes in benthic diatom communities and their relationships with environmental factors during different hydrological periods, 32 sites were sampled in the main stream of the Three Gorges Reservoir during the non-storage period (July 2015 to September 2015) and the storage period (December 2015 to March 2016). Results showed that there were significant differences in water temperature (WT), underwater light intensity (PAR), pH, conductivity (Spc), dissolved oxygen (DO), redox potential (ORP), turbidity (Tur), transparency (SD), flow rate (

In order to explore the composition of epiphytic algae and its related environmental factors, 12 sampling sites in the natural reaches and the backwater reaches (including perennial backwater sections and fluctuating backwater sections) were investigated among tributaries of the Caotang River, the Meixi River, and the Daxi River in the Fengjie district of the Chongqing section of the Three Gorges Reservoir under different hydrological regimes (i.e., storage and non-storage periods). Results showed that 103 species of epilithic algae belonging to 45 genera and 4 families are found in the 3 tributaries. This included 67 species belonging to 34 genus in the natural sections and 82 species (64 species in perennial backwater sections and 41 species in fluctuating backwater sections) belonging to 34 genera in the backwater sections. During the storage period, the dominant species in the natural sections were

As a low molecular weight protein with the ability of binding metal ions and high inducibility, metallothionein (MT) is often regarded as an important biomarker for assessment of heavy metal pollution in water environment. In the light of that the traditional process of enrichment and identification is time-consuming and complicated, we prepared a core-shell nanoparticle, gold-coated iron oxide nanoparticles (Fe3O4@Au NPs) herein. It possessed the advantages of fast response to magnetic fields and optical properties attributing to Fe3O4 and Au nanoparticles, respectively. The Fe3O4@Au nanoparticles could be used to enrich MT simply through Au–S interaction, and the purified proteins were determined by matrix assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF/MS). The results showed that the Fe3O4@Au nanoparticles could directly enrich MT from complex solutions and the detection limit could be as low as 10 fg mL−1.

Tooth development relies on sequential and reciprocal interactions between the epithelial and mesenchymal tissues, and it is continuously regulated by a variety of conserved and specific temporal-spatial signalling pathways. It is well known that suspensions of tooth germ cells can form tooth-like structures after losing the positional information provided by the epithelial and mesenchymal tissues. However, the particular stage in which the tooth germ cells start to form tooth-like structures after losing their positional information remains unclear. In this study, we investigated the reassociation of tooth germ cells suspension from different morphological stages during tooth development and the phosphorylation of Smad2/3 in this process. Four tooth morphological stages were designed in this study. The results showed that tooth germ cells formed odontogenic tissue at embryonic day (E) 14.5, which is referred to as the cap stage, and they formed tooth-like structures at E16.5, which is referred to as the early bell stage, and E18.5, which is referred to as the late bell stage. Moreover, the transforming growth factor-β signalling pathway might play a role in this process.

Bisphenol A has attracted worldwide attention due to its harmful effects on humans, animals and plants. In this study, the toxicological effects of BPA on Cylindrospermopsis raciborskii were assessed based on chlorophyll a fluorescence and transcriptome analyses. The results showed that the growth of C. raciborskii was significantly inhibited when BPA exceeded 0.1 mg L−1. A marked rise of phase J was observed at a concentration greater than 0.1 mg L−1, while a K phase appeared at 20 mg L−1. The chlorophyll a fluorescence parameters of RC/CS0, F0, φP0, φE0, and ψ0, underwent a significant decline under all treatments of BPA, whereas a significant increase in both VJ and M0 occurred under all concentrations of BPA. Additionally, ABS/RC and DIo/RC markedly increased at 10 mg L−1 and 20 mg L−1. The transcriptome analysis revealed that the genes of photosynthesis, including psbA, psbB, psbC, psbD, apcA, apcB, cpcA, and cpcB, as well as those of chlorophyll and carotenoid biosynthesis, namely hemN, acsF, chlL, chlN, chlP, crtB, pds, were all down-regulated. Moreover, BPA also inhibited the oxidative phosphorylation, glycolysis/gluconeogenesis, citrate cycle (TCA cycle), and fatty acid metabolism in C. raciborskii. Taken together, these results suggest BPA can negatively affect the expression of multiple genes and the vital energy metabolism process to arrest the growth and photosynthesis of C. raciborskii.

Background: To construct a clinicomolecular index integrating circulating Epstein-barr virus DNA (cfEBV DNA) with T- and N- categories for prognostication in nasopharyngeal carcinoma (NPC). Methods: We utilised medical records of 9,160 biopsy-proven, non-metastatic NPC cases who underwent intensity-modulated radiotherapy (IMRT) with or without chemotherapy. Decision tree modeling (DTM) and adjusted hazard ratio (AHR) methods were used to generate risk models incorporating T- and N-categories and pre-treatment cfEBV DNA load. Predictive accuracy and discrimination of the models were compared against UICC/AJCC 8th edition TNM stage and a RPA-based model. Cox regression was used for survival outcome analyses. Findings: We observed linearity between cfEBV DNA and DFS; cfEBV DNA of >2,000 copies was consistent for risk discretisation (HR >1·0) for DFS, OS and DMF in our cohort of 9,160 patients. DTM and AHR modelling using a two-tiered stratification by cfEBV DNA (≤2,000 and >2,000 copies) and Tand N- categories yielded six RGs with significantly disparate DFS (P

The 5q14.3 deletion syndrome is a heterogeneous disorder with remarkable phenotypic diversity ranging from severe to mild manifestation. In this paper, we report on a patient with 5q14.3 q21.3 deletion who exhibited the severe phenotype and died at 5.5 months. This patient can be classified as having sudden unexplained death in epilepsy (SUDEP) [Tomson et al., 2008]. The deleted region (21.02 Mb, Chr.5: 88, 047, 621-109,072,596 × 1 dn), which included MEF2C and EFNA5, was a 16.5 Mb sequence that overlapped with previously reported deletions in a patient with the mild phenotype. This study further demonstrated the complexity of clinical cytogenetic correlation of the 5q14.3 deletion.

Background Long non-coding RNAs (LncRNAs) are non-protein coding transcripts longer than 200 nucleotides in length. Instead of being "transcriptional noise", lncRNAs are emerging as a key modulator in various biological processes and disease development. Mesenchymal stem cells can be isolated from various adult tissues, such as bone marrow and dental tissues. The differentiation processes into multiple lineages, such as osteogenic differentiation, are precisely orchestrated by molecular signals in both genetic and epigenetic ways. Recently, several lines of evidence suggested the role of lncRNAs participating in cell differentiation through the regulation of gene transcriptions. And the involvement of lncRNAs may be associated with initiation and progression of mesenchymal stem cell-related diseases. Objective We aimed at addressing the role of lncRNAs in the regulation of osteogenesis of mesenchymal stem cells derived from bone marrow and dental tissues, and discussing the potential utility of lncRNAs as biomarkers and therapeutic targets for mesenchymal stem cell-related diseases. Results Numerous lncRNAs were differentially expressed during osteogenesis or odontogenesis of mesenchymal stem cells, and some of them were confirmed to be able to regulate the differentiation processes through the modifications of chromatin, transcriptional and post-transcriptional processes. LncRNAs were also associated with some diseases related with pathologic differentiation of mesenchymal stem cells. Conclusion LncRNAs involve in the osteogenic differentiation of bone marrow and dental tissuederived mesenchymal stem cells, and they could become promising therapeutic targets and prognosis parameters. However, the mechanisms of the role of lncRNAs are still enigmatic and require further investigation.

Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is a rare autosomal dominant disorder that affects craniofacial development and ovarian function. FOXL2 is the only gene known to be responsible for BPES. The majority of BPES patients show intragenic mutations of FOXL2. Recently, a 7.4 kb sequence disruption, which was 283 kb upstream of FOXL2, was identified to independently contribute to the BPES phenotype. Several breakpoints nearing FOXL2 (0 Mb to 1.2 Mb, several of which were distant from the 7.4 kb sequence disruption) have been mapped or deduced through a traditional method in BPES patients with chromosome reciprocal translocation. In this study, two BPES families with chromosome reciprocal translocation were investigated. Intragenic mutations of FOXL2 or pathogenic copy number variations were excluded for the two BPES families. All of the four breakpoints were identified at a base-precise manner using Giemsa banding and whole genome low-coverage sequencing (WGLCS). In family 01, the breakpoints were found at chr1:95,609,998 and chr3:138,879, 114 (213,132 bp upstream of FOXL2). In family 02, the breakpoints were located at chr3:138,665,431 (intragenic disruptions of FOXL2) and chr20:56,924,609. Results indicate that the intragenic and extragenic interruptions of FOXL2 can be accurately and rapidly detected using WGLCS. In addition, both the 213 kb upstream and intragenic interruptions of FOXL2 can cause BPES phenotype.

In order to trace the response of alpine plants on the Qinghai–Tibet Plateau (QTP) to the Quaternary climate oscillations, the phylogeographic history of Pomatosace filicula Maxim. was investigated in the present study. Based on sequence variations of two maternally inherited plastid markers, matK and trnH-psbA, and the biparentally inherited nuclear ribosomal internal transcribed spacer (nrITS), we estimated the population genetic structure, lineage divergence timescale, and population dynamics of P. filicula. Seven plastid haplotypes and two nrITS genotypes were identified across the range-wide sampling of 200 individuals from 24 populations. Although AMOVA revealed a high level of differentiation among populations (FST = 0.560), no significant phylogeographic structure was detected (NST = 0.503, GST = 0.518, P > 0.05). Molecular dating suggested that the divergences between major plastid lineages and nrITS genotypes occurred during the early and middle Pleistocene, and the middle Pleistocene, respectively. This species most likely survived at multiple unglaciated sites on the QTP during the Last Glacial Maximum, with most of these sites located above 4000 m a.s.l. The species probably experienced range expansion at its distribution fringe, but demographic tests did not suggest significant population size changes. We proposed that pronounced effective gene flow (Nem = 0.393) and short generation time may have obscured the phylogeographic and demographic patterns of this species. Our findings will shed new light on the Quaternary evolutionary history of the alpine flora of the QTP.

Chromosomal characteristics are important for our understanding of the evolutionary history of species diversification. However, these characteristics are as yet unknown for some plant genera, espe...

Species delimitation has been a major research focus in evolutionary biology. However, the genetic delimitation of recently diverged species varies depending on the markers examined. In this study, we aimed to examine genetic differentiation and delimitations between only two species of Pugionium Gaertn (Brassicaceae)—Pugionium cornutum (L.) Gaertn and Pugionium dolabratum Maxim—that occur in the desert habitats of central Asia and have parapatric distributions. We genotyped 169 individuals from 25 populations, using two chloroplast (cp) DNA fragments (trnV-trnM and trnS-trnfM), seven simple repeated sequence (SSR) loci and the nuclear ribosomal internal transcribed spacer (ITS). Four cp haplotypes were identified, three of which commonly occur in the two species, suggesting incomplete species-specific lineage sorting. Between-species cpDNA differentiation (F CT) was low, even lower than among populations of the same species. However, we found higher than average SSR F CT values, and both Bayesian clustering of SSR variables and maximum-likelihood genetic analyses divided all sampled individuals into two groups, agreeing well with morphological separation, although gene flow between species was obvious according to the SSR loci data. However, two types of ITS sequences were highly consistent with the morphological delimitation of the two species in all sampled individuals. These results together suggest that these two species shared numerous ancestral cpDNA polymorphisms and point to the importance of nuclear DNA (ITS or genetic accumulation at multiple loci) in delimiting recently diverged species.

As a material intended for application in hot-dip galvanization, Ti28.15Al63.4Nb8.25Y (at %) coatings were deposited onto 316L stainless steel substrate using high velocity oxygen fuel (HVOF) and atmospheric plasma spray (APS), respectively. The influence of different thermal spraying techniques on the microstructure, phase transformation, porosity, bond strength and hardness values of Ti28.15Al63.4Nb8.25Y coatings was analyzed by scanning electron microscopy (SEM), X-ray diffraction, tensile test and other analysis methods. In addition, the thermal shock test of Ti28.15Al63.4Nb8.25Y coatings was carried out to evaluate the desquamation resistance and the model of invalidation. The results indicated that HVOF Ti28.15Al63.4Nb8.25Y coatings had more uniform and compact morphology than APS Ti28.15Al63.4Nb8.25Y coating and HVOF Ti28.15Al63.4Nb8.25Y coatings have lower porosity and oxide content. The coatings processed by HVOF had higher bond strength, microhardness and thermal shock resistance and displayed better mechanical properties than that prepared by APS.

We report on a three-generation Chinese family presenting with a recognizable condition consisting of radio-ulnar synostosis, short stature, scoliosis, distinctive craniofacial features (thick vermilion to the lips, prominent eyes, and flat malar region), and a shortened and thickened femur neck. The inheritance of the trait was presumably autosomal dominant. The lack of microcephaly in the family suggested a variant of Giuffè-Tsukahara syndrome but could represent variability

Background Metaphyseal Chondrodysplasia type Schmid (MCDS) is an autosomal dominant skeletal dysplasia, characterized by coxa vara, bowlegs, short limbs and an expanded growth plate hypertrophic zone of the long bone. Previous studies have shown gene mutation of COL10A1 (collagen X, consisting three a1(X) chain) causing human MCDS. To our knowledge, there has been no COL10A1 mutation leading to elongation of the deduced α1(X) chain reported. Method A four-generation Chinese family with 11 members affected by MCDS was investigated. Mutation screening of the COL10A1 gene was carried out. Results Besides the typical MCDS features, we found an earlier onset age and a more frequently occurred knee joint pain history in the family. The following sequence analysis disclosed a novel frameshift mutation (c.2029delG) of COL10A1 , which leads to the elongation of the deduced α1(X) chain by 5 amino acids and 4 amino acids substitution. This mutation was not found in all unaffected available members and 50 healthy controls. Conclusion This is a first report of a frameshift mutation leading to elongation of the deduced α1(X) chain associated with MCDS.

The effect of microbial sulfidogenesis on As transformation and mobilization in solid phase with low Fe/As ratio is still not well known. In this study, microbial transformation and mobilization of As in the As–Fe coprecipitate with different sulfate levels were investigated using chemical extraction and K-edge XANES of As and S. Results showed that approximately 2.7, 24.4, and 83.7 % of total As were released into the aqueous phase in the low-, mid-, and high-sulfate treatments, respectively, indicating that the presence of large amounts of sulfate could enhance microbial arsenic mobilization in the As–Fe coprecipitate. In the low-sulfate treatment, As mobilization was primarily attributed to the reductive dissolution of the Fe (oxy)hydroxides and the As reduction and desorption. In the mid- and high-sulfate treatments, the reduction of arsenate and ferric iron was significantly enhanced. Complete ferric iron reduction was observed in the solid phase, implying that Fe (oxy)hydroxide was transformed to secondary minerals and may be the one of the primary causes for the enhanced As mobilization. Thermodynamic calculations predicted the formation of thioarsenite species after 35 days of incubation based on the concentration of dissolved As(III) and S(−II). Since thioarsenic species is more mobile, its formation may be one of the most important factors enhancing the As release in the high-sulfate system. The result of this study is of significance to completely predict the environmental behavior of As associated with Fe (hydr)oxides in the presence of microbial sulfidogenesis under anoxic conditions.

Infantile cystinosis (IC) is a rare autosomal recessive disorder characterized by a defect in the lysosomal-membrane transport protein, cystinosin. It serves as a prototype for lysosomal transport disorders. To date, severalCTNSmutations have been identified as the cause of the prototypic disease across different ethnic populations worldwide. However, in Asia, theCTNSmutation is very rarely reported. For the Chinese population, no literature onCTNSmutation screening for IC is available to date. In this paper, by using the whole exome sequencing and Sanger sequencing, we identified two novelCTNSsplicing deletions in a Chinese IC family, one at the donor site of exon 6 ofCTNS(IVS6+1, del G) and the other at the acceptor site of exon 8 (IVS8-1, del GT). These data give information for the genetic counseling of the IC that occurred in Chinese population.

Piebaldism is a rare autosomal dominant disorder of melanocyte development, which is mostly caused byKITgene. The key characteristics of piebaldism include localized poliosis, congenital leukoderma, and other variable manifestations. The previous study has illustrated that the homogeneousMC1R(a gene which is associated with the hair color) variant (p.I120T) coordinating withKITmutation may lead to auburn hair color and piebaldism. In this study, we have investigated a Chinese family with piebaldism and auburn hair color; the mutation screening ofKITandMC1Rgenes identified that only a splicing mutation (c. 2484+1G>A) ofKITgene cosegregated with the auburn hair color and piebaldism. The data of this study and others suggests that the KIT mutation may causes of the auburn hair color in the piebaldism patients.

Alkaptonuria (AKU) is one of the first prototypic inborn errors in metabolism and the first human disease found to be transmitted via Mendelian autosomal recessive inheritance. It is caused by HGD mutations, which leads to a deficiency in homogentisate 1,2-dioxygenase (HGD) activity. To date, several HGD mutations have been identified as the cause of the prototypic disease across different ethnic populations worldwide. However, in Asia, the HGD mutation is very rarely reported. For the Chinese population, no literature on HGD mutation screening is available to date. In this paper, we describe two novel HGD mutations in a Chinese AKU family, the splicing mutation of IVS7+1G>C, a donor splice site of exon 7, and a missense mutation of F329C in exon 12. The predicted new splicing site of the mutated exon 7 sequence demonstrated a 303bp extension after the mutation site. The F329C mutation most probably disturbed the stability of the conformation of the two loops critical to the Fe(2+) active site of the HGD enzyme.

To investigate the mechanism of the ring chromosome 9 formation by cytogenetic analysis of one case affected with ring chromosome 9 syndrome.Routine chromosome GTG-binding analysis and dual-color fluorescence in situ hybridization (FISH) with TelVision 9p and 9q probes were applied to characterize the case.The G-binding revealed that the patient had ring chromosome 9 with the following karyotype: 45,X,-9/46,XX,r(9)(p24q34)/46,XX,r(9;9)(p24q34;p24q34)[4/92/4]. The dual-color FISH analysis with TelVision 9p and TelVision 9q probes failed to detect a hybridization signal on the ring chromosome in the case, which indicated that at least 115 kb were deleted on the terminal 9p and 95 kb were deleted on the terminal 9q. Comparing to the cases reported in the literatures, our patient shared some common features of the 9p- and 9q- syndrome.The clinical features of patients with identical r(9) breakpoints present variable phenotypes. The possible cause might be the submicroscopic variation in the deletion breakpoints, variation in the ring stability, the modification of the expression of the deleted by the individual's genetic background, or the effect of changes in the fetal environment. The haploinsufficiency of genes located in the deleted regions may play critical roles in the patient phenotype as well.

To identify the origin and study the morphology of small supernumerary marker chromosome (sSMC) in Turner syndrome with 45, X/46, X, + mar karyotype.Using the conventional chromosome G-banding technique, 10 cases of Turner syndrome with 45, X/46, X, + mar chromosome karyotype were obtained, dual-color fluorescence in situ hybridization was applied to study the origin and morphology of the sSMC.In the 10 cases of Turner syndrome with 45, X/46, X, + mar karyotype, the sSMC of 7 cases was derived from X chromosome [sSMC(X)], the sSMC of 2 cases was derived from Y chromosome [sSMC(Y)] and the remaining 1 case was derived from the autosome. There were 4 cases of ring(r) chromosomes and 3 of centric minutes (min) in the 7 sSMC (X) cases. In the 2 sSMC(Y), one case was dicentric (dic) and the other was centric minute (min). The sSMC originated from the autosome was a centric minute (min).The origin of sSMC of Turner syndrome with 45, X/46, X, + mar karyotype was almost all from sex chromosomes, and rarely from autosomes. sSMC can exist as isodicentric, ring, or centric minute. The molecular cytogenetic features of the sSMC can provide useful information for genetic counseling, prenatal diagnosis and treatment of the Turner syndrome patients with a 45, X/46, X, + mar karyotype.

Renal tissues from 43 of 49 children with hepatitis B virus-associated glomerulonephritis (HBV-GN) were examined for HBV DNA by in situ hybridization (ISH) assay within the last 10 years. HBV DNA was identified in 41 of the 43 cases (95.3%). HBV DNA was distributed generally in the nucleus and cytoplasm of epithelial cells and mesangial cells of glomeruli, and epithelial cells of renal tubules. HBV DNA also existed simultaneously in renal interstitial tissues in some of these cases. The positive results from HBV DNA ISH correlated well with HBV antigen assays. The analyses implied that the more extensive the existence of HBV DNA in the nephron unit and interstitial tissue, the more severe the clinical manifestation. The duration of proteinuria in cases with HBV DNA in renal tubules was much longer than in those with no HBV DNA in renal tubules. The persistence of the HBV genome or genes in the kidney could lead to the expression of viral antigens in renal tissues and might cause cellular pathological alteration. This would support utilization of antiviral therapy, such as cytokines, in the treatment of HBV-GN.