LPCAT2 inhibits colorectal cancer progression via the PRMT1/SLC7A11 axis.

Colorectal cancer (CRC) has a high degree of heterogeneity and identifying the genetic information of individual tumor cells could help enhance our understanding of tumor biology and uncover potential therapeutic targets for CRC. In this study, we identified LPCAT2+ tumor cell populations with less malignancy than LPCAT2- tumor cells in human and mouse CRC tissues using scRNA-seq. Combining in vitro and in vivo experiments, we found that LPCAT2 could inhibit the proliferation of CRC cells by inducing ferroptosis. Mechanistically, LPCAT2 arrested PRMT1 in cytoplasm of CRC cells via regulating acetylation of PRMT1 at the K145 site. In turn, PRMT1 enhanced SLC7A11 promoter activity. Thus, LPCAT2 attenuated the positive regulatory effect of PRMT1 on SLC7A11 promoter. Notably, SLC7A11 acts as a ferroptosis regulator. Furthermore, in LPCAT2 knockout mice (LPCAT2-/-) colon cancer model, we found that LPCAT2-/- mice exhibited more severe lesions, while PRMT1 or SLC7A11 inhibitors delayed the progression. Altogether, we elucidated that LPCAT2 suppresses SLC7A11 expression by inhibiting PRMT1 nuclear translocation, thereby inducing ferroptosis in CRC cells. Moreover, inhibitors of the PRMT1/SLC7A11 axis could delay tumor progression in CRC with low LPCAT2 expression, making it a potentially effective treatment for CRC.

The TGFß2-Snail1-miRNATGFß2 Circuitry is Critical for the Development of Aggressive Functions in Breast Cancer.

There have been contradictory reports on the biological role of transforming growth factor-ßs (TGFßs) in breast cancer (BC), especially with regard to their ability to promote epithelial-mesenchymal transition (EMT). Here, we show that TGFß2 is preferentially expressed in mesenchymal-like BCs and maintains the EMT phenotype, correlating with cancer stem cell-like characteristics, growth, metastasis and chemo-resistance and predicting worse clinical outcomes. However, this is only true in ERα- BC. In ERα+ luminal-type BC, estrogen receptor interacts with p-Smads to block TGFß signalling. Furthermore, we also identify a microRNAs (miRNAs) signature (miRNAsTGFß2 ) that is weakened in TGFß2-overexpressing BC cells. We discover that TGFß2-Snail1 recruits enhancer of zeste homolog-2 to convert miRNAsTGFß2 promoters from an active to repressive chromatin configuration and then repress miRNAsTGFß2 transcription, forming a negative feedback loop. On the other hand, miRNAsTGFß2 overexpression reverses the mesenchymal-like traits in agreement with the inhibition of TGFß2-Snail1 signalling in BC cells. These findings clarify the roles of TGFß2 in BC and suggest novel therapeutic strategies based on the TGFß2-Snail1-miRNAsTGFß2 loop for a subset type of human BCs.

Priapism due to penile abscess diagnosed by ultrasonography: a case report.

BACKGROUND: Priapism is an acute medical condition requiring immediate evaluation, and depending on etiology, and potentially, the need for emergency management. Among them, priapism caused by penile abscesses is relatively rare. CASE PRESENTATION: In this case report, we report a case of priapism caused by a penile abscess found by ultrasonography, with rigidity and pain in the corpus cavernosum, but no penile deviation. The patient was treated with an abscess incision and drainage. CONCLUSION: Ultrasonography plays an important role in the diagnosis of penile abscess formation, and once the diagnosis is made, early treatment should be given to improve the adverse outcomes.

XBP1-elicited environment by chemotherapy potentiates repopulation of tongue cancer cells by enhancing miR-22/lncRNA/KAT6B-dependent NF-κB signalling.

BACKGROUND: Tumour repopulation initiated by residual tumour cells in response to cytotoxic therapy has been described clinically and biologically, but the mechanisms are unclear. Here, we aimed to investigate the mechanisms for the tumour-promoting effect in dying cells and for tumour repopulation in surviving tongue cancer cells. METHODS: Tumour repopulation in vitro and in vivo was represented by luciferase activities. The differentially expressed cytokines in the conditioned medium (CM) were identified using a cytokine array. Gain or loss of function was investigated using inhibitors, neutralising antibodies, shRNAs and ectopic overexpression strategies. RESULTS: We found that dying tumour cells undergoing cytotoxic therapy increase the growth of living tongue cancer cells in vitro and in vivo. Dying tumour cells create amphiregulin (AREG)- and basic fibroblast growth factor (bFGF)-based extracellular environments via cytotoxic treatment-induced endoplasmic reticulum stress. This environment stimulates growth by activating lysine acetyltransferase 6B (KAT6B)-dependent nuclear factor-kappa B (NF-κB) signalling in living tumour cells. As direct targets of NF-κB, miR-22 targets KAT6B to repress its expression, but long noncoding RNAs (lncRNAs) (XLOC_003973 and XLOC_010383) counter the effect of miR-22 to enhance KAT6B expression. Moreover, we detected increased AREG and bFGF protein levels in the blood of tongue cancer patients with X-box binding protein-1 (XBP1) activation in tumours under cytotoxic therapy and found that XBP1 activation is associated with poor prognosis of patients. We also detected activation of miR-22/lncRNA/KAT6B/NF-κB signalling in recurrent cancers compared to paired primary tongue cancers. CONCLUSIONS: We identified the molecular mechanisms of cell death-induced tumour repopulation in tongue cancer. Such insights provide new avenues to identify predictive biomarkers and effective strategies to address cancer progression.

[Efficacy of Zhibai Dihuang Decoction on energy metabolism of spermatogenic cells in Ureaplasma urealyticum-infected rats: A study based on AMPK and PPARα signaling pathways].

OBJECTIVE: To study the effect of the serum containing Zhibai Dihuang Decoction (ZDD) on the energy metabolism of spermatogenic cells infected with Ureaplasma urealyticum (UU) in rats and its action mechanism. METHODS: Healthy male SD rats were randomly divided into six groups, normal control, UU-infection (UUI) model control, doxycycline, and low-, medium- and high-dose ZDD-containing serum. After successful establishment of the UUI model in vivo in the latter five groups, the rats in the normal control group were treated with simple serum and those in the latter five with respective agents. Then primary spermatogenic cells were harvested from the rats for examination of the apoptosis of spermatogenic cells, contents of lactate dehydrogenase (LDH) and adenosine triphosphate (ATP), glucose disposal rate (GDR) and expressions of AMPK and PARα proteins in the spermatogenic cells, and other related parameters. RESULTS: The apoptosis rate of the spermatogenic cells was dramatically increased in the UUI model controls compared with that in the normal controls (ï¼»49.24 ± 0.86ï¼½% vs ï¼»10.09 ± 0.52ï¼½%, P < 0.01), but significantly decreased in the doxycycline and low-, medium- and high-dose ZDD groups (ï¼»11.21 ± 1.02ï¼½%, ï¼»30.64 ± 0.99ï¼½%, ï¼»35.54 ± 1.17ï¼½% and ï¼»42.95 ± 1.31ï¼½%) in comparison with that in the UUI model control group (P < 0.01).The content of LDH in the spermatogenic cells was also remarkably increased in the UUI model controls compared with that in the normal controls (ï¼»201.12 ± 2.88ï¼½ vs ï¼»60.72 ± 1.83ï¼½) mU/ml, P < 0.01), but significantly decreased in the doxycycline and low-, medium- and high-dose ZDD groups (ï¼»90.66 ± 1.61ï¼½, ï¼»94.74 ± 1.20ï¼½, ï¼»101.24 ± 2.03ï¼½ and ï¼»111.04 ± 3.35ï¼½ mU/ml) in comparison with that in the UUI model control group (P < 0.01). The GDR in the spermatogenic cells was markedly reduced in the UUI model controls compared with that in the normal controls (ï¼»49.42 ± 1.70ï¼½% vs ï¼»99.86 ± 1.26ï¼½%, P < 0.01), but significantly elevated in the doxycycline and low-, medium- and high-dose ZDD groups (ï¼»86.90 ± 2.03ï¼½%, ï¼»84.14 ± 1.21ï¼½%, ï¼»80.30 ± 1.37ï¼½% and ï¼»75.18 ± 1.76ï¼½% in comparison with that in the UUI model control group (P < 0.01). The content of ATP was also dramatically decreased in the UUI model controls compared with that in the normal controls (ï¼»19.76 ± 1.46ï¼½ vs ï¼»58.94 ± 1.95ï¼½ µmol/L, P < 0.01), but significantly increased in the doxycycline and low-, medium- and high-dose ZDD groups (ï¼»48.34 ± 1.34ï¼½, ï¼»42.82 ± 1.30ï¼½, ï¼»38.70 ± 2.03ï¼½ and ï¼»34.78 ± 0.82ï¼½ µmol/L) in comparison with that in the UUI model control group (P < 0.01). The mitochondrial membrane potential was remarkably elevated in the UUI model controls compared with that in the normal controls (ï¼»8.53 ± 0.71ï¼½% vs ï¼»2.43 ± 0.25ï¼½%, P < 0.01), but markedly reduced in the doxycycline and low-, medium- and high-dose ZDD groups (ï¼»3.92 ± 0.36ï¼½%, ï¼»4.43 ± 0.27ï¼½%, ï¼»4.65 ± 0.22ï¼½% and ï¼»4.88 ± 0.10ï¼½% in comparison with that in the UUI model control group (P < 0.01). The phosphorylation levels of AMPK and PPARα proteins were significantly up-regulated in the UUI model controls compared with that in the normal controls (P < 0.01), but down-regulated in a dose-dependent manner in the ZDD groups. CONCLUSIONS: Zhibai Dihuang Decoction can significantly improve the damage to the mitochondrial structure and inhibit UU infection-induced apoptosis of spermatogenic cells and secretion of LDH by increasing the ATP content and GDR and regulating the phosphorylation of AMPK and PARα signaling pathway.

M1 Bone Marrow-Derived Macrophage-Derived Extracellular Vesicles Inhibit Angiogenesis and Myocardial Regeneration Following Myocardial Infarction via the MALAT1/MicroRNA-25-3p/CDC42 Axis.

Myocardial infarction (MI) is a severe cardiovascular disease. Some M1 macrophage-derived extracellular vesicles (EVs) are involved in the inhibition of angiogenesis and acceleration dysfunction during MI. However, the potential mechanism of M1 phenotype bone marrow-derived macrophages- (BMMs-) EVs (M1-BMMs-EVs) in MI is largely unknown. This study sought to investigate whether M1-BMMs-EVs increased CDC42 expression and activated the MEK/ERK pathway by carrying lncRNA MALAT1 and competitively binding to miR-25-3p, thus inhibiting angiogenesis and myocardial regeneration after MI. After EV treatment, the cardiac function, infarct size, fibrosis, angiogenesis, and myocardial regeneration of MI mice and the viability, proliferation and angiogenesis of oxygen-glucose deprivation- (OGD-) treated myocardial microvascular endothelial cells (MMECs) were assessed. MALAT1 expression in MI mice, cells, and EVs was detected. MALAT1 downstream microRNAs (miRs), genes, and pathways were predicted and verified. MALAT1 and miR-25-3p were intervened to evaluate EV effects on OGD-treated cells. In MI mice, EV treatment aggravated MI and inhibited angiogenesis and myocardial regeneration. In OGD-treated cells, EV treatment suppressed cell viability, proliferation, and angiogenesis. MALAT1 was highly expressed in MI mice, OGD-treated MMECs, M1-BMMs, and EVs. Silencing MALAT1 weakened the inhibition of EV treatment on OGD-treated cells. MALAT1 sponged miR-25-3p to upregulate CDC42. miR-25-3p overexpression promoted OGD-treated cell viability, proliferation, and angiogenesis. The MEK/ERK pathway was activated after EV treatment. Collectively, M1-BMMs-EVs inhibited angiogenesis and myocardial regeneration following MI via the MALAT1/miR-25-3p/CDC42 axis and the MEK/ERK pathway activation.

Integrative Analysis of DNA Methylation and Transcriptome Identifies a Predictive Epigenetic Signature Associated With Immune Infiltration in Gliomas.

Glioma is the most common primary brain tumor with poor prognosis and high mortality. The purpose of this study was to use the epigenetic signature to predict prognosis and evaluate the degree of immune infiltration in gliomas. We integrated gene expression profiles and DNA methylation data of lower-grade glioma and glioblastoma to explore epigenetic differences and associated differences in biological function. Cox regression and lasso analysis were used to develop an epigenetic signature based on eight DNA methylation sites to predict prognosis of glioma patients. Kaplan-Meier analysis showed that the overall survival time of high- and low-risk groups was significantly separated, and ROC analysis verified that the model had great predictive ability. In addition, we constructed a nomogram based on age, sex, 1p/19q status, glioma type, and risk score. The epigenetic signature was obviously associated with tumor purity, immune checkpoints, and tumor-immune infiltrating cells (CD8+ T cells, gamma delta T cells, M0 macrophages, M1 macrophages, M2 macrophages, activated NK cells, monocytes, and activated mast cells) and thus, it may find application as a guide for the evaluation of immune infiltration or in treatment decisions in immunotherapy.

Disruption of FOXO3a-miRNA feedback inhibition of IGF2/IGF-1R/IRS1 signaling confers Herceptin resistance in HER2-positive breast cancer.

Resistance to Herceptin represents a significant challenge for successful treatment of HER2-positive breast cancer. Here, we show that in Herceptin-sensitive cells, FOXO3a regulates specific miRNAs to control IGF2 and IRS1 expression, retaining basic IGF2/IGF-1R/IRS1 signaling. The basic activity maintains expression of PPP3CB, a subunit of the serine/threonine-protein phosphatase 2B, to restrict FOXO3a phosphorylation (p-FOXO3a), inducing IGF2- and IRS1-targeting miRNAs. However, in Herceptin-resistant cells, p-FOXO3a levels are elevated due to transcriptional suppression of PPP3CB, disrupting the negative feedback inhibition loop formed by FOXO3a and the miRNAs, thereby upregulating IGF2 and IRS1. Moreover, we detect significantly increased IGF2 in blood and IRS1 in the tumors of breast cancer patients with poor response to Herceptin-containing regimens. Collectively, we demonstrate that the IGF2/IGF-1R/IRS1 signaling is aberrantly activated in Herceptin-resistant breast cancer via disruption of the FOXO3a-miRNA negative feedback inhibition. Such insights provide avenues to identify predictive biomarkers and effective strategies overcoming Herceptin resistance.

Cardiac T1 and T2 Mapping Showed Myocardial Involvement in Recovered COVID-19 Patients Initially Considered Devoid of Cardiac Damage.

BACKGROUND: Myocardial injury has been found using magnetic resonance imaging in recovered coronavirus disease 2019 (COVID-19) patients unselected or with ongoing cardiac symptoms. PURPOSE: To evaluate for the presence of myocardial involvement in recovered COVID-19 patients without cardiovascular symptoms and abnormal serologic markers during hospitalization. STUDY TYPE: Prospective. POPULATION: Twenty-one recovered COVID-19 patients and 20 healthy controls (HC). FIELD STRENGTH/SEQUENCE: 3.0 T, cine, T2-weighted imaging, T1 mapping, and T2 mapping. ASSESSMENT: Cardiac ventricular function includes end-diastolic volume, end-systolic volume, stroke volume, cardiac output, left ventricle (LV) mass, and ejection fraction (EF) of LV and right ventricle (RV), and segmental myocardial T1 and T2 values were measured. STATISTICAL TESTS: Student's t-test, univariate general linear model test, and chi-square test were used for analyses between two groups. Ordinary one-way analyses of variance or Kruskal-Wallis H test were used for analyses between three groups, followed by post-hoc analyses. RESULTS: Fifteen (71.43%) COVID-19 patients had abnormal magnetic resonance findings, including raised myocardial native T1 (5, 23.81%) and T2 values (10, 47.62%), decreased LVEF (1, 4.76%), and RVEF (2, 9.52%). The segmental myocardial T2 value of COVID-19 patients (49.20 [46.1, 54.6] msec) was significantly higher than HC (48.3 [45.2, 51.7] msec) (P < 0.001), while the myocardial native T1 value showed no significant difference between COVID-19 patients and HC. The myocardial T2 value of serious COVID-19 patients (52.5 [48.1, 57.1] msec) was significantly higher than unserious COVID-19 patients (48.8 [45.9, 53.8] msec) and HC (48.3 [45.2, 51.7]) (P < 0.001). COVID-19 patients with abnormally elevated D-dimer, C-reactive protein, or lymphopenia showed higher myocardial T2 values than without (all P < 0.05). DATA CONCLUSION: Cardiac involvement was observed in recovered COVID-19 patients with no preexisting cardiovascular disease, no cardiovascular symptoms, and elevated serologic markers of myocardial injury during the whole course of COVID-19. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 5.

lncRNA LINC01057 promotes mesenchymal differentiation by activating NF-κB signaling in glioblastoma.

Long non-coding RNAs (lncRNAs) have been potentially identified as new diagnostic markers, prognostic factors and therapeutic targets in cancer. The acquisition of a mesenchymal (MES) phenotype in glioblastomas (GBMs) results into therapeutic resistance and poor clinical outcomes. The correlation between lncRNAs and MES differentiation remains elusive. Here, we report that LINC01057 as a lncRNA is overexpressed in GBMs, especially in MES subtype. LINC01057 knockdown suppresses proliferation, invasion and radioresistance of GBM cells in vitro, and tumor growth in vivo. LINC01057 knockdown leads to loss of MES signature in MES subpopulation of GBM cells, but LINC01057 overexpression promotes MES differentiation in proneural (PN) subpopulation. LINC01057 interacts with IKKα and maintains IKKα nucleus localization, leading to effective chromatin accessibility at NF-κB responsive promoters via histone modification and final NF-κB activation. IKKα knockdown disrupts the effect of LINC01057 overexpression on PN to MES transition (PMT). LINC01057 level is negatively correlated with patient prognosis in MES-subtype GBM. Collectively, our findings uncover LINC01057 as a regulator of NF-κB signaling to promote MES differentiation and a potential target for therapeutic intervention for MES-subtype GBM.

Acute cardiac injury in adult hospitalized COVID-19 patients in Zhuhai, China.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has already became a public health emergency of international concern. COVID-19 related cardiac injury remains largely unclear. METHODS: We retrospectively analyzed demographic, clinical, laboratory and cardiovascular imaging data of all consecutively admitted adult COVID-19 patients in Zhuhai, China from January 17th, 2020 to February 18th, 2020. RESULTS: A total of 93 patients were included in the study. Acute cardiac injury was found in 9 (9.7%) COVID-19 patients with median level of hypersensitive cardiac troponin I (hs-cTnI) to be 0.085 µg/L (IQR 0.027-0.560 µg/L). Compared with patients without cardiac injury, the median age of patients with cardiac injury was significantly older (65.0 vs. 44.0, P<0.05), hypertension was significantly more common (44.4% vs. 14.3%, P<0.05), and the proportion of severe-critical cases were greater (77.8% vs. 17.9%, P<0.05). Patients with cardiac injury were more likely have elevation of N-terminal proBNP (NT-proBNP) in comparison (66.7% vs. 10.0%, P<0.05). There was no significant difference in echocardiographic parameters between patients with and without cardiac injury. Multivariable logistic regression analysis indicated that older age (OR: 1.093, 95% CI: 1.011-1.182) and increased NT-proBNP (OR: 10.979, 95% CI: 2.024-59.555) were independent risk factors for cardiac injury. Cardiac magnetic resonance (CMR) imaging performed on three patients at around one month after they underwent significant hs-cTnI elevation showed that they had underlying cardiovascular comorbidities. CONCLUSIONS: Acute cardiac injury was seen in the minority of hospitalized COVID-19 patients in Zhuhai, China. Older age and increased NT-proBNP were associated with acute cardiac injury. REGISTRATION NUMBER: ChiCTR2000030952.

A prognostic 11-DNA methylation signature for lung squamous cell carcinoma.

BACKGROUND: Lung squamous cell carcinoma (LUSC), as the second frequent subtype of lung cancer, causes lots of mortalities primarily due to a lack of precise prognostic markers and timely treatment intervention. Previous studies have constructed several risk prognostic models based on DNA methylation sites in multiple tumors, whereas, DNA methylation signature of LUSC remains to be built, and its predictive value need to be evaluated. METHODS: The genome-wide DNA methylation data of LUSC samples was obtained from The Cancer Genome Atlas dataset. Univariate Cox analysis and the least absolute shrinkage and selection operator (LASSO) were implemented to identify DNA methylation sites related to overall survival of LUSC patients. Thus, we performed multivariate Cox regression to establish a DNA methylation signature. The Kaplan-Meier (K-M) survival curves and time-dependent receiver operating characteristic (ROC) curves were plotted to estimate the prognostic power of the signature. Comparison with other known prognostic biomarkers, our DNA methylation signature showed higher predictive specificity and sensitivity. In addition, multivariate Cox regression screened out independent prognostic factors and constructed a nomogram. RESULTS: Several statistical methods were performed to construct an 11-DNA methylation signature. LUSC patients were divided into low- and high-risk group based on risk score, and high-risk group had a shorter survival time. According to the results of K-M and ROC analyses, the 11-DNA methylation signature showed significant sensitivity and specificity in predicting the LUSC patients' overall survival. Finally, we integrated some independent prognostic factors (risk score, metastasis stage, and tobacco smoking history) to construct a nomogram, which has excellent prognostic power and may provide guidance for the therapeutic strategies. CONCLUSIONS: We constructed the first risk prognosis model based on DNA methylation site in LUSC, which showed better predictive ability. In addition, a nomogram integrating the DNA methylation signature, metastasis stage, and tobacco smoking history was developed.

[Accumulation and Translocation of Cd in Brassica rapa Under the Influence of Selenium].

Cadmium (Cd) is a highly toxic heavy metal. Brassica rapa (pak choi) is a vastly common vegetable, which readily accumulates Cd. Given the current conditions of Cd contamination in domestic soil, it is important to reduce Cd accumulation in the edible part of pak choi. Research has shown that selenium (Se) can regulate Cd uptake by plants. Cd accumulation (three cultivars) and Cd uptake kinetics in pak choi were investigated under hydroponic conditions. Results showed that the three levels of selenite significantly reduced Cd content in the Hangzhouyoudonger shoot by 50%, while the levels in Suzhouqinggen and Shanghaiqing shoots were not significantly decreased with elevated levels of selenite. Selenite reduces the Cd translocation factors, and higher levels had more obvious effects; 50 µmol·L-1 of selenite significantly decreased the factors by 50% in Hangzhouyoudonger and Suzhouqinggen shoots. Selenite also increased iron (Fe) and manganese (Mn) contents in pak choi, especially in the Hangzhouyoudonger shoot, where 50 µmol·L-1 increased the Fe content by approximately 50%. In the uptake kinetics of Cd, both selenite and selenate significantly increased Cd uptake rates and Vmax by over 100%. Therefore, Se could reduce Cd accumulation in pak choi. This also depended on the tested cultivar. Therefore, reduction effects of Se on the Cd content mainly stemmed from the alteration of Cd translocation in pak choi instead of the uptake competition between Cd and Se.

[Toxicity of Chromium to Root Growth of Barley as Affected by Chromium Speciation and Soil Properties].

Tri-and hexavalent chromium have different chemical properties, and their levels of toxicity to plants are different. However, there is no limit set by the soil environmental quality risk control standard for Cr(Ⅲ) or Cr(Ⅵ). Therefore, studying the ecological toxicity of Cr has important implications for protecting the environment. Based on the dynamics of the Cr(Ⅲ) and Cr(Ⅵ) levels in soil solution collected from eight soils, the toxicity thresholds of the two Cr forms to barley roots were investigated through model calculation and correlation analysis under different soil properties. The results showed that both Cr forms and the soil properties had significant effects on the root length of barley. The effective concentrations of Cr(Ⅲ) added to the soils that led to 10% inhibition (EC10), 50% inhibition (EC50), and no-observed-effect concentrations (NOEC) were significantly higher than those of Cr(Ⅵ). The EC50 of Cr(Ⅲ) ranged from 298.8 to 2014.1 mg·kg-1 (6.7-fold variation); the EC50 of Cr(Ⅵ) ranged from 8.0 to 126.6 mg·kg-1 (15.8-fold variation). Under the same soil conditions, the EC50 of Cr(Ⅲ) was 2.8 to 101.7 times higher than that of Cr(Ⅵ), suggesting the higher phytotoxicity of Cr(Ⅵ) than Cr(Ⅲ). Correlation analysis showed that the pH and soil organic matter were the main factors that influenced the Cr toxicity thresholds, as indicated by the root length of barley. The concentration of chromium in the soil solution was below the detection limit of the TAS-990 when Cr(Ⅲ) was applied at 1280 mg·kg-1 (or less) to soils, whereas for Cr(Ⅵ), the level was 40 mg·kg-1 (or less). Cr(Ⅲ) adsorption to the soil was significantly stronger than that of Cr(Ⅵ). The toxicity of Cr(Ⅵ) was significantly higher than that of Cr(Ⅲ), which was also influenced by soil properties.

Impact of coronavirus disease 2019 on pulmonary function in early convalescence phase.

OBJECTIVE: This study investigated the influence of Coronavirus Disease 2019 (COVID-19) on lung function in early convalescence phase. METHODS: A retrospective study of COVID-19 patients at the Fifth Affiliated Hospital of Sun Yat-sen University were conducted, with serial assessments including lung volumes (TLC), spirometry (FVC, FEV1), lung diffusing capacity for carbon monoxide (DLCO),respiratory muscle strength, 6-min walking distance (6MWD) and high resolution CT being collected at 30 days after discharged. RESULTS: Fifty-seven patients completed the serial assessments. There were 40 non-severe cases and 17 severe cases. Thirty-one patients (54.3%) had abnormal CT findings. Abnormalities were detected in the pulmonary function tests in 43 (75.4%) of the patients. Six (10.5%), 5(8.7%), 25(43.8%) 7(12.3%), and 30 (52.6%) patients had FVC, FEV1, FEV1/FVC ratio, TLC, and DLCO values less than 80% of predicted values, respectively. 28 (49.1%) and 13 (22.8%) patients had PImax and PEmax values less than 80% of the corresponding predicted values. Compared with non-severe cases, severe patients showed higher incidence of DLCO impairment (75.6%vs42.5%, p = 0.019), higher lung total severity score (TSS) and R20, and significantly lower percentage of predicted TLC and 6MWD. No significant correlation between TSS and pulmonary function parameters was found during follow-up visit. CONCLUSION: Impaired diffusing-capacity, lower respiratory muscle strength, and lung imaging abnormalities were detected in more than half of the COVID-19 patients in early convalescence phase. Compared with non-severe cases, severe patients had a higher incidence of DLCO impairment and encountered more TLC decrease and 6MWD decline.

LncRNA SNORD3A specifically sensitizes breast cancer cells to 5-FU by sponging miR-185-5p to enhance UMPS expression.

Breast cancer is the most common cancer type in women. Long non-coding RNAs (lncRNAs) have been reported as potential new diagnostic markers, prognostic factors, and therapeutic targets in cancer. However, the specific roles and mechanisms of lncRNAs in breast cancer remain to be elucidated. Here we demonstrated the downregulation of lncRNA SNORD3A in breast cancer cells and tissues and verified its non-protein-coding property. SNORD3A overexpression had no effect on cell proliferation but specifically sensitized breast cancer cells to 5-fluorouracil (5-FU) in vitro and in vivo. Mechanistically, SNORD3A exerts its effect via enhancing uridine monophosphate synthetase (UMPS) protein expression. SNORD3A acts as a competing endogenous RNA for miR-185-5p, leading to UMPS protein upregulation. miR-185-5p overexpression disrupted the effect of SNORD3A on chemosensitization to 5-FU in vitro and in vivo. Moreover, Meis1 overexpression transcriptionally promotes SNORD3A expression, and Meis1 is downregulated in breast cancer cells and tissues. In breast cancer tissues, SNORD3A level positively correlates with Meis1 and UMPS protein levels, whereas miR-185-5p level negatively correlates with UMPS protein level. High SNORD3A transcript and Meis1 and UMPS protein levels predicts a better outcome, but high miR-185-5p level predicts a worse outcome in breast cancer patients receiving 5-FU-based chemotherapy. Our findings indicate that Meis1-regulated SNORD3A specifically sensitizes breast cancer cells to 5-FU via enhancing UMPS expression. The SNORD3A-UMPS axis may serve as a potential biomarker and therapeutic target to improve the efficacy of 5-FU-based chemotherapy for breast cancer patients.

Household Transmission of SARS-CoV-2, Zhuhai, China, 2020.

BACKGROUND: To illustrate the extent of transmission, identify affecting risk factors and estimate epidemiological modeling parameters of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in household setting. METHODS: We enrolled 35 confirmed index cases and their 148 household contacts, January 2020-February 2020, in Zhuhai, China. All participants were interviewed and asked to complete questionnaires. Household contacts were then prospectively followed active symptom monitoring through the 21-day period and nasopharyngeal and/or oropharyngeal swabs were collected at 3-7 days intervals. Epidemiological, demographic, and clinical data (when available) were collected. RESULTS: Assuming that all these secondary cases were infected by their index cases, the second infection rate in household context is 32.4% (95% confidence interval [CI]: 22.4%-44.4%), with 10.4% of secondary cases being asymptomatic. Multivariate analysis showed that household contacts with underlying medical conditions, a history of direct exposure to Wuhan and its surrounding areas, and shared vehicle with an index patient were associated with higher susceptibility. Household members without protective measures after illness onset of the index patient seem to increase the risk for SARS-CoV-2 infection. The median incubation period and serial interval within household were estimated to be 4.3 days (95% CI: 3.4-5.3 days) and 5.1 days (95% CI: 4.3-6.2 days), respectively. CONCLUSION: Early isolation of patients with coronavirus disease 2019 and prioritizing rapid contact investigation, followed by active symptom monitoring and periodic laboratory evaluation, should be initiated immediately after confirming patients to address the underlying determinants driving the continuing pandemic.

Melatonin receptor protects cardiomyocyte against oxidative stress-induced apoptosis through the MAPK-ERK signaling pathway.

Context: The role of melatonin receptor in cardiomyocyte oxidative stress has not been investigated.Aim: The aim of our study is to verify the beneficial effects of melatonin receptors on cardiomyocyte viability under oxidative stress.Methods: Cardiomyocytes were treated with hydrogen peroxide. Cell viability was measured via MTT assay and TUNEL staining. Then, anti-oxidative factors measurement and signaling pathway analysis were performed via qPCR and ELISA.Results: Melatonin receptor activation could attenuate hydrogen peroxide-mediated cardiomyocyte death via reducing apoptosis. At the molecular levels, melatonin receptor activation reduced inflammation response and maintained mitochondrial membrane potential. In addition, melatonin receptor activation is associated with decreased oxidative stress and increased anti-oxidative factors. Finally, we found that melatonin receptor activation triggered an elevation in the activity and expression of ERK pathway and blockade of ERK pathway would abolish the beneficial effects exerted by melatonin receptors activation on cardiomyocyte survival under oxidative stress.Conclusions: Our data suggest that melatonin receptor could attenuate oxidative stress injury in cardiomyocyte through regulation of the ERK signaling pathway.

lncRNA THAP9-AS1 Promotes Pancreatic Ductal Adenocarcinoma Growth and Leads to a Poor Clinical Outcome via Sponging miR-484 and Interacting with YAP.

PURPOSE: Long noncoding RNAs (lncRNA) have been observed in various cancer types. Our bioinformatic analysis of existing databases demonstrated overexpression of lncRNA THAP9-AS1 in pancreatic ductal adenocarcinoma (PDAC). We aimed to investigate the roles and mechanisms of THAP9-AS1 in PDAC. EXPERIMENTAL DESIGN: The overexpression of THAP9-AS1 in samples of patients with pancreatic cancer was characterized and was associated with clinical outcomes. The nonprotein coding property of the THAP9-AS1 was verified. Various in vitro and in vivo experiments were performed to investigate the interaction between THAP9-AS1 and YAP signaling. RESULTS: We demonstrated that lncRNA THAP9-AS1 is overexpressed in PDAC in multiple patient sample sets, which is significantly associated with poor outcome of patients with PDAC. THAP9-AS1 promotes PDAC cells growth both in vitro and in vivo. THAP9-AS1 exerts its effects via enhancing YAP signaling. Ectopic YAP expression overcame the effects of THAP9-AS1 knockdown. Inversely, YAP knockdown diminished the effects of THAP9-AS1 overexpression. THAP9-AS1 acts as a competing endogenous RNA for miR-484, leading to YAP upregulation. Moreover, THAP9-AS1 binds to YAP protein and inhibits the phosphorylation-mediated inactivation of YAP by LATS1. Reciprocally, YAP/TEAD1 complex promotes THAP9-AS1 transcription to form a feed-forward circuit. Importantly, THAP9-AS1 level positively correlates with YAP expression in PDAC tissues. YAP overexpression also predicts a poor outcome in patients with PDAC. CONCLUSIONS: Our findings indicate that THAP9-AS1 plays an important role in PDAC growth via enhancing YAP signaling, which in turn also modulates THAP9-AS1 transcription. THAP9-AS1/YAP axis may serve as a potential biomarker and therapeutic target for PDAC treatment.