Targeting USP1-dependent KDM4A protein stability as a potential prostate cancer therapy

The histone demethylase lysine-specific demethylase 4A (KDM4A) is reported to be overexpressed and plays a vital in multiple cancers through controlling gene expression by epigenetic regulation of H3K9 or H3K36 methylation marks. However, the biological role and mechanism of KDM4A in prostate cancer (PC) remain unclear. Herein, we reported KDM4A expression was upregulation in phosphatase and tensin homolog knockout mouse prostate tissue. Depletion of KDM4A in PC cells inhibited their proliferation and survival in vivo and vitro. Further studies reveal that USP1 is a deubiquitinase that regulates KDM4A K48-linked deubiquitin and stability. Interestingly, we found c-Myc was a key downstream effector of the USP1-KDM4A/androgen receptor axis in driving PC cell proliferation. Notably, upregulation of KDM4A expression with high USP1 expression was observed in most prostate tumors and inhibition of USP1 promotes PC cells response to therapeutic agent enzalutamide. Our studies propose USP1 could be an anticancer therapeutic target in PC

Associations of first-trimester TMAO and its precursors with gestational diabetes mellitus: a pilot prospective cohort study

AimsWe aimed to provide a comprehensive understanding of the associations between Trimethylamine-N-oxide (TMAO), its precursor and gestational diabetes mellitus (GDM).MethodsIn this prospective study, 940 women were included in a Chinese single -center pregnant cohort. First trimester plasma concentrations of TMAO and its precursors (betaine, choline, L-carnitine, and trimethylamine) were measured using UPLC-ESI-MS/MS. GDM and specific abnormal glucose levels (fasting glucose; one-hour post-load glucose, 1-h PG; two-hour post load glucose, 2-h PG; and 1-h PG ≥ 8.6 mmol/L) were assessed through oral glucose tolerance tests. First-trimester plasma concentrations of TMAO and its precursors were divided into quartile groups (bottom, Q1; middle, Q2 and Q3; top, Q4).ResultsAmong the subjects, 167 (17.8%) were found to have GDM. After adjusting for potential covariates, the lower groups (Q1) of L-carnitine were associated with a higher risk of GDM compared to the reference group (middle quartiles). The OR (95% CI, p) was1.56 (1.04, 2.35, p = 0.032) for L-carnitine. Specifically, the associations were mainly derived from L-carnitine and abnormal 1-h PG. The ORs (95% CI, p) were 2.00 (1.24, 3.24, p = 0.005).ConclusionLow plasma levels (bottom vs. middle quartiles) of L-carnitine the first-trimester pregnancy were associated with a higher risk of GDM and abnormal 1-h PG in Chinese pregnant women

HLA-matched sibling transplantation with G-CSF mobilized PBSCs and BM decreases GVHD in adult patients with severe aplastic anemia

<p>Abstract</p> <p>Background</p> <p>Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment for severe aplastic anemia (SAA). However, graft failure and graft-versus-host disease (GVHD) are major causes of the early morbidity in Allo-HSCT.</p> <p>Methods</p> <p>To reduce graft failure and GVHD, we treated fifteen patients with SAA using high- dose of HSCT with both G-CSF mobilized PB and BMSCs from HLA-identical siblings to treat patients with SAA.</p> <p>Results</p> <p>All patients had successful bone marrow engraftment. Only one patient had late rejection. Median time to ANC greater than 0.5 × 10⁹/L and platelet counts greater than 20 × 10⁹/L was 12 and 16.5 days, respectively. No acute GVHD was observed. The incidence of chronic GVHD was 6.67%. The total three-year probability of disease-free survival was 79.8%.</p> <p>Conclusion</p> <p>HSCT with both G-CSF mobilized PB and BMSCs is a promising approach for heavily transfused and/or allo-immunized patients with SAA.</p

Associations of serum concentrations of metal nutrients with postpartum anemia among pregnant Chinese women: A large retrospective cohort study

Background and AimsThe association between serum concentrations of metal nutrients in pregnancy and postpartum anemia has not been widely studied. This study aimed to determine this association in a large retrospective cohort study.MethodsWe included 14,829 Chinese women with singleton pregnancies. Serum concentrations of metals before 28 weeks of gestation, the occurrence of postpartum anemia and other potential covariates were obtained from their laboratory or medical records. Cox regression and restricted cubic spline regression models were used to explore the relationship between serum concentrations of metal nutrients in pregnancy and postpartum anemia.ResultsAfter adjustment for covariates, higher concentrations of iron (Fe), magnesium (Mg) and zinc (Zn) and lower concentrations of copper (Cu) were associated with a lower risk of postpartum anemia. Compared with those whose serum concentrations of metal nutrients were in the bottom quintile (Q1), the hazard ratios (HRs) of those whose serum concentrations of metal nutrients were in the top quintile (Q5) were 0.57 (95% confidence interval (CI): 0.50, 0.64) for Fe, 0.67 (95% CI: 0.60, 0.76) for Mg, 0.82 (95% CI: 0.73, 0.93) for Zn, and 1.44 (95% CI: 1.28, 1.63) for Cu. L-shaped curve relationships were found between increasing concentrations of Fe, Mg, and Zn and incidence of postpartum anemia. Higher serum concentrations of Cu were associated with an increased risk of postpartum anemia. Serum concentrations of Fe in Q5 were associated with a lower risk of postpartum anemia when they coincided with serum concentrations of Mg in Q5, Zn in Q5, or Cu in Q1.ConclusionHigher serum concentrations of Fe, Mg, and Zn, and lower serum concentrations of Cu were associated with a lower risk of postpartum anemia among pregnant women

&lt;i&gt;In situ&lt;/i&gt; resistance analysis of MgB&lt;sub&gt;2&lt;/sub&gt; formation process from Mg(BH&lt;sub&gt;4&lt;/sub&gt;)&lt;sub&gt;2&lt;/sub&gt;

Mg(BH&lt;sub&gt;4&lt;/sub&gt;)&lt;sub&gt;2&lt;/sub&gt; was previously studied as a promising hydrogen storage material, because of its high gravimetric storage capacities for hydrogen and suitable thermodynamic properties. Mg(BH&lt;sub&gt;4&lt;/sub&gt;)&lt;sub&gt;2&lt;/sub&gt; began to decompose at about 300 ℃, and formed MgB&lt;sub&gt;2&lt;/sub&gt; at the end of hydrogen desorption process with the weight content of 14.9% of hydrogen lost. Aside from the prominent hydrogen storage property, the decomposition process from Mg(BH&lt;sub&gt;4&lt;/sub&gt;)&lt;sub&gt;2&lt;/sub&gt; to MgB&lt;sub&gt;2&lt;/sub&gt; can be a potential method for fabricating superconducting MgB&lt;sub&gt;2&lt;/sub&gt; at a low sintering temperature. In this paper, MgB&lt;sub&gt;2&lt;/sub&gt; bulk was prepared by an &lt;i&gt;in-situ&lt;/i&gt; reaction, using the Mg(BH&lt;sub&gt;4&lt;/sub&gt;)&lt;sub&gt;2&lt;/sub&gt; pressed block as a precursor. The resistance change of the sample was monitored during the Mg(BH&lt;sub&gt;4&lt;/sub&gt;)&lt;sub&gt;2&lt;/sub&gt; decomposition process and the resistance-temperature (&lt;i&gt;R&lt;/i&gt;-&lt;i&gt;T&lt;/i&gt;) curve of this process was recorded. Phase of MgH&lt;sub&gt;2&lt;/sub&gt;, Mg and B were formed as the block slowly release its hydrogen before MgB&lt;sub&gt;2&lt;/sub&gt; occurred. According to the &lt;i&gt;R&lt;/i&gt;-&lt;i&gt;T&lt;/i&gt; curve, the phase formation of MgB&lt;sub&gt;2&lt;/sub&gt; started in a relatively low temperature of 410 ℃. Because MgB&lt;sub&gt;2&lt;/sub&gt; was critically formed by Mg and B derived from Mg(BH&lt;sub&gt;4&lt;/sub&gt;)&lt;sub&gt;2&lt;/sub&gt;, we can compare our formation temperature with previous study on MgB&lt;sub&gt;2&lt;/sub&gt; prepared by Mg and B in different particle size. The fitting result indicated that the particle size of Mg and B harvest from Mg(BH&lt;sub&gt;4&lt;/sub&gt;)&lt;sub&gt;2&lt;/sub&gt; decomposition was only 3.4 nm on average. The nearly atomic level mixture of Mg and B resulted in a high chemical reactivity, which was the main reason for low sintering temperature. X-ray diffraction results showed that the purity of MgB&lt;sub&gt;2&lt;/sub&gt; was 95.2%, and the size of MgB&lt;sub&gt;2&lt;/sub&gt; grains was 10–18 nm. SEM images showed that the MgB&lt;sub&gt;2&lt;/sub&gt; bulk had a porous structure and poor connectivity, which was caused by large amount the hydrogen release during the decomposition. MgB&lt;sub&gt;2&lt;/sub&gt; nanofibers can also be observed inside the bulk. In the superconductivity test, the superconducting transition temperature of the bulk was 35 K. After all, such &lt;i&gt;in situ&lt;/i&gt; method to fabricate MgB&lt;sub&gt;2&lt;/sub&gt; showed a great advantage in some aspects, as its low-cost precursors, low sintering temperature, small grain-size and high superconducting transition temperature in the formed MgB&lt;sub&gt;2&lt;/sub&gt;, which have the potential in industrial scale fabrication of MgB&lt;sub&gt;2&lt;/sub&gt; bulks and wires.</jats:p

Identification of a novel PAX6 mutation in a Chinese family with aniridia

Abstract Background This study aims to investigate the clinical characterization and causative genetic defect of a four-generation Chinese family with autosomal dominant aniridia. Methods The recruited family members underwent comprehensive routine and ophthalmic examinations, and Sanger sequencing was performed to screen the mutation in PAX6. Results A novel heterozygous PAX6 deletion c.435_445delTAGCGAAAAGC (p.Ser146ThrfsX9) in exon 7 was identified in all affected individuals, but this was absent in any of the unaffected family members and in the 200 unrelated controls. Conclusion A novel deletion in the PAX6 gene was identified in a Chinese family associated with aniridia, which expands the spectrum of the PAX6 mutation and its associated phenotype

Effects of Rotational Tillage on Soil Physicochemical Properties and Crop Yield in a Rice–Wheat Double Cropping Area

This paper aims to explore issues related to destruction of soil nutrients and structure in a rice-wheat double-cropping area caused by over-tillage prior to rice cultivation. A three-year cycle of rotation tillage pattern (RT), consisting of “no-tillage–no-tillage–plough”, with a straw-returning and direct rice-seeding technology, was designed and tested, and was compared with continuous no-tillage pattern (CN) and conventional ploughing &amp; rotary tillage (PR). The soil rotation experiment in the rice-wheat double-cropping region is located on the southeastern coast of Shandong Province, with a warm, temperate, humid monsoon climate and paddy soil type. Comparison experiments were conducted on the three farming patterns over a period of 3 years, continuously measuring soil physical and chemical properties and crop yields. The results showed that under the same straw-returning conditions, RT significantly increased soil macroaggregates content and enhanced their stability within 0~30 cm (p &lt; 0.05). RT significantly reduced the bulk density of 0~30 cm soil to below 1.5 g/cm3, which was beneficial to crop root growth (p &lt; 0.05). Meanwhile, RT significantly increased the contents of soil organic carbon, total nitrogen, and available phosphorus, and the nutrients are evenly distributed in 0~30 cm layer (p &lt; 0.05). Another result was that the RT significantly increased the rice panicle length, grains number per panicle, and thousand-grain weigh. The crop yield was not significantly different from that of PR, but significantly higher than that of CN (p &lt; 0.05). At the same time, cultivation measures prior to rice cultivation had some after-effects on wheat; the RT significantly increased the average tillers, effective panicle number, effective panicle grain number, and thousand-seed weight of wheat; and the wheat yields were 10.5% and 13.3% higher than that of CN and PR, respectively. This study provides a theoretical reference for improving tillage patterns in rice-wheat double-cropping areas.</jats:p