The Integrated Analysis of miRNome and Degradome Sequencing Reveals the Regulatory Mechanisms of Seed Development and Oil Biosynthesis in Pecan (Carya illinoinensis).

Pecan seed oil is a valuable source of essential fatty acids and various bioactive compounds; however, the functions of microRNAs and their targets in oil biosynthesis during seed development are still unknown. Here, we found that the oil content increased rapidly in the three early stages in three cultivars, and that oleic acid was the predominant fatty acid component in the mature pecan embryos. We identified, analyzed, and validated the expression levels of miRNAs related to seed development and oil biosynthesis, as well as their potential target genes, using small RNA sequencing data from three stages (120, 135, and 150 days after flowering). During the seed development process, 365 known and 321 novel miRNAs were discovered. In total, 91 known and 181 novel miRNAs were found to be differentially expressed, and 633 target genes were further investigated. The expression trend analysis revealed that the 91 known miRNAs were classified into eight groups, approximately two-thirds of which were up-regulated, whereas most novel miRNAs were down-regulated. The qRT-PCR and degradome sequencing data were used to identify five miRNA- target pairs. Overall, our study provides valuable insights into the molecular regulation of oil biosynthesis in pecan seeds.

Safety and effectiveness of tunneled peripherally inserted central catheters versus conventional PICC in adult cancer patients.

OBJECTIVES: This study aimed to compare the safety and effectiveness of tunneled peripherally inserted central catheters (T-PICC) vs. conventional PICCs (C-PICC) in adult cancer patients. METHODS: A multicentre randomized controlled trial was conducted between April 2021 and January 2022 in seven hospitals in China. 564 participants were randomly assigned to T-PICC or C-PICC. These data were collected and compared: the baseline characteristics and catheterization-related characteristics, periprocedural complications, and long-term complications. RESULTS: Five-hundred fifty-three participants (aged, 52.6 ± 12.3 years; female, 39.1%) were ultimately analyzed. No significant differences in periprocedural complications were found between the T-PICC and C-PICC groups (all p > 0.05). Compared with C-PICC, T-PICC significantly reduced the incidence of long-term complications (26.4% vs. 39.9%, p < 0.001). Specifically, reduced complications were found in central line-associated bloodstream infection (1.8% vs. 5.1%, p = 0.04), thrombosis (1.1% vs. 4.0%, p = 0.03), catheter dislodgement (4.7% vs. 10.1%, p = 0.01), non-infectious oozing (17.3% vs. 28.6%, p = 0.002), local infection (3.6% vs. 7.6%, p = 0.04), skin irritation (6.1% vs. 10.9%, p = 0.046), and reduced unplanned catheter removal (2.2% vs. 7.2%, p = 0.005). No significant differences were found between T-PICC and C-PICC regarding catheter occlusion (6.5% vs. 5.8%, p = 0.73) or skin damage (2.2% vs. 2.9%, p = 0.58). CONCLUSION: T-PICC is safe and effectively reduces long-term complications. CLINICAL RELEVANCE STATEMENT: The tunneled technique is effective in reducing PICC-related long-term complications. Thus, it is recommended for cancer patients at high risk of PICC-related complications. TRIAL REGISTRATION: The registration number on https://www.chictr.org.cn/ is ChiCTR2100044632. The name of the trial registry is "A multicenter randomized controlled study of clinical use of tunneled vs. non-tunneled PICC". KEY POINTS: Cather-related complications are associated with the technique of catheterization. Compared with conventional PICC, tunneled PICC reduced catheter-related long-term complications. Tunneled PICC placement provides an alternative catheterization method for cancer patients.

Comparative Different Interventions to Improve Exercise Adherence in Patients in the Postoperative Breast Cancer Phase of Care: A Network Meta-analysis.

BACKGROUND: Global Cancer Statistics 2020 reported that breast cancer had exceeded lung cancer as the most frequently diagnosed cancer. Surgery is the primary treatment modality for breast cancer, but postoperative upper limb dysfunction often occurs; functional exercise can alleviate this and restore upper limb function. However, exercise compliance is low in postoperative breast cancer patients; thus, many studies have been conducted in recent years to improve patient compliance with exercise. OBJECTIVE: The aim of this study was to compare the effectiveness of different interventions to improve exercise adherence in postoperative breast cancer patients. METHODS: We searched PubMed, Cochrane Library, Web of Science, EMBASE, Wan Fang, CNKI, VIP, and CBM databases for eligible studies. Exercise adherence rate and quality-of-life difference were assessed as outcomes. Sensitivity analysis and inconsistency detection were performed to evaluate whether the exclusion of high-risk studies affected the validity. Risk of bias was assessed using the risk-of-bias table in RevMan 5.4. Surface under the cumulative ranking was used to estimate the rankings among different interventions. RESULTS: Twenty-five randomized controlled trials involving 9 interventions were included, and the network meta-analysis results showed that patients in the pedometer + counseling group had the best exercise adherence. CONCLUSION: Pedometer + counseling care measures are recommended to improve exercise adherence in postoperative breast cancer patients. IMPLICATIONS FOR PRACTICE: Oncology nurses can improve patients' exercise compliance through counseling and by giving them pedometers to wear.

A novel variant in the GJB6 gene in a large Chinese family with a unique phenotype of Clouston syndrome.

Clouston syndrome (OMIM #129500), also known as hidrotic ectodermal dysplasia type 2, is a rare autosomal dominant skin disorder. To date, four mutations in the GJB6 gene, G11R, V37E, A88V, and D50N, have been confirmed to cause this condition. In previous studies, the focus has been mainly on gene sequencing, and there has been a lack of research on clinical manifestations and pathogenesis. To confirm the diagnosis of this pedigree at the molecular level and summarize and analyse the clinical phenotype of patients and to provide a basis for further study of the pathogenesis of the disease, we performed whole-exome and Sanger sequencing on a large Chinese Clouston syndrome pedigree. Detailed clinical examination included histopathology, hair microscopy, and scanning electron microscopy. We found a novel heterozygous missense variant (c.134G>C:p.G45A) for Clouston syndrome. We identified a new clinical phenotype involving all nail needling pain in all patients and found a special honeycomb hole structure in the patients' hair under scanning electron microscopy. Our data reveal that a novel variant (c.134G>C:p.G45A) plays a likely pathogenic role in this pedigree and highlight that genetic testing is necessary for the diagnosis of Clouston syndrome.

LncRNA FIRRE functions as a tumor promoter by interaction with PTBP1 to stabilize BECN1 mRNA and facilitate autophagy.

Long non-coding RNAs (lncRNAs) play critical functions in various cancers. Firre intergenic repeating RNA element (FIRRE), a lncRNA located in the nucleus, was overexpressed in colorectal cancer (CRC). However, the detailed mechanism of FIRRE in CRC remains elusive. Results of RNA sequence and qPCR illustrated overexpression of FIRRE in CRC cell lines and tissues. The aberrant expression of FIRRE was correlated with the migration, invasion, and proliferation in cell lines. In accordance, it was also associated with lymphatic metastasis and distant metastasis in patients with CRC. FIRRE was identified to physically interact with Polypyrimidine tract-binding protein (PTBP1) by RNA pull-down and RNA immunoprecipitation (RIP). Overexpression of FIRRE induced the translocation of PTBP1 from nucleus to cytoplasm, which was displayed by immunofluorescence and western blot. In turn, delocalization of FIRRE from nucleus to cytoplasm is observed after the loss of PTBP1. The RNA-protein complex in the cytoplasm directly bound to BECN1 mRNA, and the binding site was at the 3' end of the mRNA. Cells with FIRRE and PTBP1 depletion alone or in combination were treated by Actinomycin D (ACD). Results of qPCR showed FIRRE stabilized BECN1 mRNA in a PTBP1-medieated manner. In addition, FIRRE contributed to autophagy activity. These findings indicate FIRRE acts as an oncogenic factor in CRC, which induces tumor development through stabilizing BECN1 mRNA and facilitating autophagy in a PTBP1-mediated manner.

rs12537 Is a Novel Susceptibility SNP Associated With Estrogen Receptor Positive Breast Cancer in Chinese Han Population.

Genetic testing is widely used in breast cancer and has identified a lot of susceptibility genes and single nucleotide polymorphisms (SNPs). However, for many SNPs, evidence of an association with breast cancer is weak, underlying risk estimates are imprecise, and reliable subtype-specific risk estimates are not in place. A recent genome-wide long non-coding RNA (lncRNA) association study in Chinese Han has verified a genetic association between rs12537 and breast cancer. This study is aimed at investigating the association between rs12537 and the phenotype. We collected the clinical information of 5,634 breast cancer patients and 6,308 healthy controls in the early study. And χ2 test was used for the comparison between different groups in genotype. The frequency of genotypic distribution among SNP rs12537 has no statistically significant correlation with family history (p = 0.8945), menopausal status (p = 0.3245) or HER-2 (p = 0.2987), but it is statistically and significantly correlated with ER (p = 0.004006) and PR (p = 0.01379). Most importantly, compared to the healthy control, rs12537 variant is significantly correlated with ER positive patients and the p-value has reached the level of the whole genome (p = 1.66E-08 <5.00E-08). Furthermore, we found rs12537 associated gene MTMR3 was lower expressed in breast cancer tissues but highly methylated. In conclusion, our findings indicate that rs12537 is a novel susceptibility gene in ER positive breast cancer in Chinese Han population and it may influence the methylation of MTMR3.

Loss-of-function variants in FSIP1 identified by targeted sequencing are associated with one particular subtype of mucosal melanoma.

BACKGROUND: Mucosal melanoma is a tumor caused by the malignant transformation of pigment-producing cells and can arise from any mucosal tissue where melanocytes are present. Due to its rarity, the mucosal melanoma subtype is poorly described, and its genetic characteristics are infrequently studied. The discovery or confirmation of new mucosal melanoma susceptibility genes will provide important insights for the study of its pathogenesis. MATERIALS AND METHODS: We performed deep targeted sequencing of 100 previously reported melanoma-related genes in 39 mucosal melanoma samples and a gene-level loss-of-function (LOF) variant enrichment analysis for mucosal melanoma from different incidence sites. RESULTS: We detected 7,589 variants in these samples, and 484 were LOF variants (gain or loss of a stop codon, missense, and splice site). Four different gene-level enrichment analyses revealed that FSIP1 (fibrous sheath interacting protein 1) is a susceptibility gene for oral mucosal melanoma (OR = 0.33, PChi = 4.05 × 10-2, Pburden = 3.06 × 10-2, Pskat = 3.01 × 10-2, Pskato = 3.01 × 10-2), whereas the different methods did not detect a significant susceptibility gene for the other subtypes. CONCLUSIONS: In our study, a susceptibility gene for oral mucosal melanoma was confirmed in a Chinese Han population, and these findings contribute to a better genetic understanding of mucosal melanoma of different subtypes.

Joint effects of chronic exposure to environmentally relevant levels of nonylphenol and cadmium on the reproductive functions in male rockfish Sebastiscus marmoratus.

Nonylphenol (NP) and Cadmium (Cd) are two common contaminants that can be detected in aquatic environments. Nevertheless, the combined toxicity of NP and Cd at environmentally relevant concentrations in aquatic organisms has not been thoroughly characterized to date. In the present study, the interactions between NP and Cd on male Sebastiscus marmoratus were studied. After 21 days of exposure, the brain aromatase activity was observed to be significantly induced by 100 ng/L NP and 40 µg/L Cd, whereas all of the concentrations of co-treatment resulted in an increase in brain aromatase activity. Additionally, NP could also reduce plasma testosterone concentration, while NP, Cd and their mixture could induce plasma 17ß-estradiol (E2) concentration and VTG concentration. The interactions between NP and Cd on the reproductive physiology were antagonism. Our results also support the notion of using these indicators as biomarkers for exposure to EDCs and further extend the boundary of biomonitoring to environmental levels.

[Inhibition of proliferation of adult T-cell leukemia cells by celastrol].

We studied the effect of celastrol on the proliferation and apoptosis of adult T-cell leukemia (ATL) cells. After treating adult T-cell leukemia cell lines with different concentrations of celastrol, we analyzed the cell proliferation by MTT and colony formation assays. Flow cytometry was conducted to detect cell apoptosis by Annexin V-FITC/PI staining. Western blotting and dual-luciferase reporter assay were done to study the mechanism how celastrol suppressed the growth of adult T-cell leukemia cells. Celastrol could significantly inhibit the proliferation of adult T-cell leukemia cells, and induce apoptosis of ATL cells. With the increase of the concentration of celastrol, the ratio of Bax/Bcl-2 protein was up-regulated. The Caspase-3/7 protein was cleaved and activated after treatment with celastrol. Moreover, the expression of HTLV-1-encoded viral protein Tax was significantly inhibited in the celastrol treated cells. Taken together, these results indicated that celastrol effectively inhibited the proliferation of adult T-cell leukemia cells by regulating the expression of Bcl-2 family protein, and induced cell apoptosis by activating Caspase dependent pathway. In addition, celastrol could inhibit the expression of viral protein Tax. This study will provide an experimental basis for the clinical application of celastrol in the treatment of adult T-cell leukemia.

Long Noncoding RNA ANRIL Supports Proliferation of Adult T-Cell Leukemia Cells through Cooperation with EZH2.

Adult T-cell leukemia (ATL) is a highly aggressive T-cell malignancy induced by human T-cell leukemia virus type 1 (HTLV-1) infection. Long noncoding RNA (lncRNA) plays a critical role in the development and progression of multiple human cancers. However, the function of lncRNA in HTLV-1-induced oncogenesis has not been elucidated. In the present study, we show that the expression level of the lncRNA ANRIL was elevated in HTLV-1-infected cell lines and clinical ATL samples. E2F1 induced ANRIL transcription by enhancing its promoter activity. Knockdown of ANRIL in ATL cells repressed cellular proliferation and increased apoptosis in vitro and in vivo As a mechanism for these actions, we found that ANRIL targeted EZH2 and activated the NF-κB pathway in ATL cells. This activation was independent of the histone methyltransferase (HMT) activity of EZH2 but required the formation of an ANRIL/EZH2/p65 ternary complex. A chromatin immunoprecipitation assay revealed that ANRIL/EZH2 enhanced p65 DNA binding capability. In addition, we observed that the ANRIL/EZH2 complex repressed p21/CDKN1A transcription through H3K27 trimethylation of the p21/CDKN1A promoter. Taken together, our results implicate that the lncRNA ANRIL, by cooperating with EZH2, supports the proliferation of HTLV-1-infected cells, which is thought to be critical for oncogenesis.IMPORTANCE Human T-cell leukemia virus type 1 (HTLV-1) is the pathogen that causes adult T-cell leukemia (ATL), which is a unique malignancy of CD4+ T cells. A role for long noncoding RNA (lncRNA) in HTLV-1-mediated cellular transformation has not been described. In this study, we demonstrated that the lncRNA ANRIL was important for maintaining the proliferation of ATL cells in vitro and in vivo ANRIL was shown to activate NF-κB signaling through forming a ternary complex with EZH2 and p65. Furthermore, epigenetic inactivation of p21/CDKN1A was involved in the oncogenic function of ANRIL. To the best of our knowledge, this is the first study to address the regulatory role of the lncRNA ANRIL in ATL and provides an important clue to prevent or treat HTLV-1-associated human diseases.

Association Study Confirmed Three Breast Cancer-Specific Molecular Subtype-Associated Susceptibility Loci in Chinese Han Women.

BACKGROUND: Breast cancer is a heterogeneous and polygenic disease that can be divided into different molecular subtypes based on histological and genomic features. To date, numerous susceptibility loci of breast cancer have been discovered by genome-wide association studies and may expand the genetic features. However, few loci have been further studied according to molecular subtypes. MATERIALS AND METHODS: We genotyped 23 recently discovered single nucleotide polymorphisms using the Sequenom iPLEX platform in a female Chinese cohort of 3,036 breast cancer patients (2,935 samples matched molecular subtypes) and 3,036 healthy controls. RESULTS: Through a stratification analysis, 5q11.2/MAP3K1 (rs16886034, rs16886364, rs16886397, rs1017226, rs16886448) and 7q32.3/LINC-PINT (rs4593472) were associated with Luminal A, and 10q26.1/FGFR2 (rs35054928) was associated with Luminal B. CONCLUSION: In our study, breast cancer-specific molecular subtype-associated susceptibility loci were confirmed in Chinese Han women, which contributes to a better genetic understanding of breast cancer in different molecular subtypes. IMPLICATIONS FOR PRACTICE: To date, genome-wide association studies have identified more than 90 susceptibility loci associated with breast cancer. However, few loci have been further studied according to molecular subtype. The results of this study are that breast cancer-specific molecular subtype-associated susceptibility loci were confirmed in Chinese Han women, which contributes to a better genetic understanding of breast cancer in different molecular subtypes.

Association study confirms two susceptibility loci for breast cancer in Chinese Han women.

To date, many loci associated with breast cancer have been identified through genome-wide association studies; most of these studies were conducted using populations of European descent. Thus, it is not clear whether these susceptibility loci are also risk factors for Chinese populations. We selected and genotyped 32 single nucleotide polymorphisms (SNPs) using the Sequenom iPLEX platform in a female Chinese cohort of 3036 breast cancer cases and 3036 healthy controls. A total of 23 SNPs passed the quality control test. The associations of these SNPs with disease susceptibility were assessed using logistic regression, adjusting for age. The Bonferroni correction was used to conservatively account for multiple testing, and the threshold for statistical significance was P < 2.17 × 10(-3) (0.05/23). We confirmed ten risk-associated variants within three reported breast cancer susceptibility loci in a Chinese Han population: 5q11.2 (rs16886181, P = 5.29 × 10(-6), OR = 1.19; rs1017226, P = 5.24 × 10(-4), OR = 1.22; rs16886034, P = 2.00 × 10(-3), OR = 1.21; rs16886113, P = 1.24 × 10(-3), OR = 1.20; rs16886364, P = 9.20 × 10(-4), OR = 1.21; rs16886397, P = 1.17 × 10(-3), OR = 1.20; rs16886448, P = 1.62 × 10(-3,)OR = 1.20; and rs2229882, P = 5.14 × 10(-4), OR = 1.31), 5q14.3 (rs421379, P = 2.83 × 10(-13), OR = 1.83), and 10q26.1 (rs35054928, P = 7.73 × 10(-6), OR = 1.18). The 10q26.1 locus was found to be a susceptibility locus for breast cancer in Chinese Han women in our previous studies. 5q11.2 and 5q14.3 are confirmed here for the first time as susceptibility loci for breast cancer in Chinese Han women. This study reports three breast cancer susceptibility loci that were previously identified in European populations and are also risk factors for Chinese populations. This study may extend the genetic basis of breast cancer in Chinese Han women and highlight the contribution of multiple variants of modest effect.

[HTLV-1 bZIP Factor (HBZ): Roles in HTLV-1 Oncogenesis].

Human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus demonstrated to be associated with human disease. Infection by the HTLV-1 can cause T-cell leukemia (ATL) in adults. HTLV-1 bZIP factor (HBZ) is a viral protein encoded by the minus strand of the HTLV-1 provirus. Among the regulatory and accessory genes of HTLV-1, HBZ is the only gene that remains intact and which is expressed consistently in all patients with ATL. Moreover, HBZ has a critical role in the leukemogenesis of ATL. Here, we review the function of HBZ in the oncogenesis of HTLV-1 and its molecular mechanism of action.

Association study of susceptibility loci with specific breast cancer subtypes in Chinese women.

To determine whether recent genome-wide association studies that reported 45 susceptibility loci in European women are also risk factors for breast cancer in Chinese women. We selected and genotyped 40 single nucleotide polymorphisms (SNPs) using the Sequenom iPlex platform in a female Chinese cohort of 2,901 breast cancer cases and 2,789 healthy controls. We evaluated these SNPs with the risk of breast cancer and further by estrogen receptor (ER) status, progestin (PR) status, human epidermal growth factor receptor-2 (HER-2) status, and four breast cancer subtypes (Luminal A type, Luminal B type, HER-2 overexpression type and Basal-like type). We first confirmed that the SNP rs9693444 on 8p12 was associated with breast cancer in Chinese women (P = 6.44 × 10(-4)). Furthermore, we identified four susceptibility loci that were associated with specific tumor subtypes. Statistically significant differences were detected with the association of rs6828523 (4q34.1/ADAM29) with ER-positive breast cancer (P = 1.27 × 10(-3)) and the association of rs4849887 (2q14.2) with PR-positive breast cancer (P = 1.29 × 10(-3)). Of the four breast cancer subtypes, the associations of rs12493607 (3p24.1/TGFBR2) with HER-2 overexpression in breast cancer (P = 1.09 × 10(-3)) and rs11075995 (16q12.2/FTO) with basal-like breast cancer (P = 1.64 × 10(-4)) were statistically significant. This study is the first to show that these 5 susceptibility loci (8p12, 4q34.1/ADAM29, 2q14.2, 3p24.1/TGFBR2, and 16q12.2/FTO) correlate with breast cancer (overall and specific subtypes) in Chinese women, which has improved our understanding of the genetic basis of specific breast cancer subtypes.