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Purpose: To establish a method for the simultaneous determination of multi-components of Rhizoma coptidis steamed with rice wine (RCRW), and to provide a reference for assessing its standard of quality. Method: Chromatographic separation was performed on a high performance liquid chromatography (HPLC) system to determine the characteristic fingerprint of RCRW. The mobile phase consisted of acetonitrile (A) and 0.1% trifluoroacetic acid (B), with gradients of B as follows: 15 - 20% from 0 - 30 min; 20 - 25% from 30 - 50 min; 25 - 35% for 50 - 60 min, and 35% for 60 - 70 min. Results: In the multiple reaction monitoring mode, eight components of RCRW were isolated by HPLCphoto-diode array (PDA) method. A fingerprint of the RCRW was established and 8 peaks were calibrated. The method was further validated in terms of linearity (R² > 0.9993), precision (relative standard deviation, RSD < 1.51%); repeatability (RSD < 2.98%) and stability (RSD < 1.93%). Mean recovery rate ranged from 96.2 to 103.8%, while RSD values ranged from 0.92 to 2.88%. Conclusion: These results show that HPLC-PDA method is accurate and feasible, and that they provide a reference for further comprehensive and effective quality control of RCRW. [ABSTRACT FROM AUTHOR]

The article discusses the findings of the study about the impact in the changes in the patterns of histone modification. It states that the changes in histone modification which is a posttranslational modification of the component proteins of chromatin may lead to differential splicing outcomes. It mentions that the integrated mechanism which serves to ensure accuracy and efficiency of splicing regulation can reinforce splicing choices that are also regulated by the same splicing factors.

Neurofibromatosis type 1 (NF1) is one of the most common heritable autosomal dominant disorders. Alternative splicing modulates the function of neurofibromin, the NF1 gene product, by inserting the in-frame exon 23a into the region of NF1 mRNA that encodes the GTPase-activating protein-related domain. This insertion, which is predominantly skipped in neurons, reduces the ability of neurofibromin to regulate Ras by 10-fold. Here, we report that the neuron-specific Hu proteins control the production of the short protein isoform by suppressing inclusion of NF1 exon 23a, while TIA-1/TIAR proteins promote inclusion of this exon. We identify two binding sites for Hu proteins, located upstream and downstream of the regulated exon, and provide biochemical evidence that Hu proteins specifically block exon definition by preventing binding of essential splicing factors. In vitro analyses using nuclear extracts show that at the downstream site, Hu proteins prevent binding of U1 and U6 snRNPs to the 5' splice site, while TIAR increases binding. Hu proteins also decrease U2AF binding at the 3' splice site located upstream of exon 23a. In addition to providing the first mechanistic insight into tissue-specific control of NF1 splicing, these studies establish a novel strategy whereby Hu proteins regulate RNA processing. [ABSTRACT FROM AUTHOR]

Although multiple regulatory elements and protein factors are known to regulate the non-neuronal pathway of alternative processing of the calcitonin/calcitonin gene-related peptide (CGRP) pre-mRNA, the mechanisms controlling the neuron-specific pathway have remained elusive. Here we report the identification of Fox-1 and Fox-2 proteins as novel regulators that mediate the neuron-specific splicing pattern. Fox-1 and Fox-2 proteins function to repress exon 4 inclusion, and this effect depends on two UGCAUG elements surrounding the 3′ splice site of the calcitonin-specific exon 4. In neuron-like cells, mutation of a subset of UGCAUG elements promotes the non-neuronal pattern in which exon 4 is included. In HeLa cells, overexpression of Fox-1 or Fox-2 protein decreases exon 4 inclusion. Fox-1 and Fox-2 proteins interact with the UGCAUG elements specifically and regulate splicing by blocking U2AF65 binding to the 3′ splice site upstream of exon 4. We further investigated the inter-relationship between the UGCAUG silencer elements and the previously identified intronic and exonic splicing regulatory elements and found that exon 4 is regulated by an intricate balance of positive and negative regulation. These results define a critical role for Fox-1 and Fox-2 proteins in exon 4 inclusion of calcitonin/CGRP pre-mRNA and establish a regulatory network that controls the fate of exon 4. [ABSTRACT FROM AUTHOR]

In the title compound, [Ni(C4H3N2O2)2(H2O)4] or [Ni(HDHPM)2(H2O)4] (H2DHPM = 4,6-dihydroxy­pyrimidine), the NiII atom, on an inversion centre, is six-coordinated by two N atoms from two HDMPM− ligands and four O atoms from four water mol­ecules. A three-dimensional supra­molecular structure is formed through π–π and hydrogen-bonding inter­actions. [ABSTRACT FROM AUTHOR]

AIM: To evaluate the therapeutic effect of combined phacovitrectomy with membrane peeling and intraocular lens (IOL) implantation in patients with severe idiopathic epiretinal membrane (iERM) and concurrent cataract. METHODS: A total of 34 eyes from 34 patients who underwent phacovitrectomy and epiretinal membrane (ERM) peeling at the First Affiliated Hospital of Zhejiang University between 2015 and 2017. The best-corrected visual acuity (BCVA) and central foveal thickness (CFT) were measured preoperatively and at 1, 3, 6mo and 1y postoperatively. Temporal changes and bivariate correlations of these parameters were analyzed. RESULTS: Mean logMAR BCVA improved and CFT decreased significantly (P

Objectives: The objective of the study is to investigate the feasibility and efficacy of urethroplasty with a Buck's fascia integral-covering technique (BFIC) to wrap and restore the normal anatomical structure of the penis in one-stage hypospadias surgery.Methods: One-stage surgeries for hypospadias management were performed using BFIC from January 2016 to September 2020 at four high-volume medical centers in China. The technique integrates Buck's fascia with glans wings to mobilize and wrap the urethra and restore penile anatomical relationships. The clinical data, postoperative follow-up data, and complications were recorded, and the results were analyzed.Results: A total of 1,386 patients were included in the study: 1,260 cases of primary hypospadias and 126 cases of re-operations; distal in 382 cases (27.6%), mid-shaft in 639 (46.1%), proximal in 365 (26.3%); tubularized incised plate (TIP) in 748 cases, inlay-graft in 124, onlay-graft in 49, Mathieu in 28, free-tube graft urethroplasty in 406, and 31 of hybrid procedures. One thousand one hundred forty-two patients (82.4%) were found to have penile curvature (>10°) after artificial erection and all corrected by dorsal plication/s or transection of the urethra plate (UP) simultaneously. The median followed-up time was 27 months (6–62). A total of 143 (10.3%) complications were recorded: 114 (9.0%) in the primary operations and 29 (23%) in the re-operations, 15 (3.9%) in distal hypospadias, 61 (9.5%) in mid-shaft, and 67 (18.4%) in proximal. The complication rate in UP preservation and transection was 10.1 and 10.8%, respectively. Of all case complications, there were 73 (5.2%) of fistula, 10 (0.6%) of dehiscence, 22 (1.6%) of meatal stenosis, 21 (1.5%) of stricture, 6 (0.7%) of diverticulum, and resident curvature in 11 cases (1.2%). The overall complication rate in TIP and free-tube procedure was 9.8 and 9.9%, respectively, and fistula occurred in primary TIP of 33 cases (4.9%).Conclusions: Buck's fascia with the glans can be used as an integral covering technique in one-stage distal to proximal hypospadias and primary or re-operative hypospadias repair. It is safe, feasible, and effective for the repair of hypospadias.

Context: Coptidis rhizome (CR), also known as Huanglian in Chinese, is the rhizome of Coptis chinensis Franch., C. deltoidea C.Y. Cheng et Hsiao, or C. teeta Wall (Ranunculaceae). It has been widely used to treat bacillary dysentery, diabetes, pertussis, sore throat, aphtha, and eczema in China. Objectives: The present paper reviews the latest advances of CR, focusing on the botany, phytochemistry, traditional usages, pharmacokinetics, pharmacology and toxicology of CR and its future perspectives. Methods: Studies from 1985 to 2018 were reviewed from books; PhD. and MSc. dissertations; the state and local drug standards; PubMed; CNKI; Scopus; the Web of Science; and Google Scholar using the keywords Coptis, Coptidis Rhizoma, Huanglian, and goldthread. Results: Currently, 128 chemical constituents have been isolated and identified from CR. Alkaloids are the characteristic components, together with organic acids, coumarins, phenylpropanoids and quinones. The extracts/compounds isolated from CR cover a wide pharmacological spectrum, including antibacterial, antivirus, antifungal, antidiabetic, anticancer and cardioprotective effects. Berberine is the most important active constituent and the primary toxic component of CR. Conclusions: As an important herbal medicine in Chinese medicine, CR has the potential to treat various diseases. However, further research should be undertaken to investigate the clinical effects, toxic constituents, target organs and pharmacokinetics, and to establish criteria for quality control, for CR and its related medications. In addition, the active constituents, other than alkaloids, in both raw and processed products of CR should be investigated.

Cancer has become a significant public health problem with high disease burden and mortality. At present, radiotherapy and chemotherapy are the main means of treating cancer, but they have shown serious safety problems. The severity of this problem has caused further attention and research on effective and safe cancer treatment methods. Polysaccharides are natural products with anti-cancer activity that are widely present in a lot of plants, and many studies have found that inducing apoptosis of cancer cells is one of their important mechanisms. Therefore, this article reviews the various ways in which plant polysaccharides promote apoptosis of cancer cells. The major apoptotic pathways involved include the mitochondrial pathway, the death receptor pathway, and their upstream signal transduction such as MAPK pathway, PI3K/AKT pathway, and NF-κB pathway. Moreover, the paper has also been focused on the absorption and toxicity of plant polysaccharides with reference to extant literature, making the research more scientific and comprehensive. It is hoped that this review could provide some directions for the future development of plant polysaccharides as anticancer drugs in pharmacological experiments and clinical researches.

Sedimentary phosphorus (P) forms are important representatives of P sources and their bioavailability as well as the potential of sediments to release P in water. In this study, surface sediments along a transect of the Changjiang Estuary and two transects along the Andong salt marsh in the southwest of Hangzhou Bay were subjected to the elucidation of sedimentary P species using the standards, measurements, and testing (SMT) and sequential extraction (SEDEX) methods. The results showed that the mean sedimentary P forms elucidated by the SMT method were as follows: organic P (OP; ∼11–14 mg/kg; ∼30–45% of total P; TP) > apatite P (∼5–15 mg/kg; ∼21–36% TP) > Fe/Al-P (∼8–14 mg/kg; ∼31–34% TP), with inorganic P (IP) composing 54–70% of TP. The mean sedimentary P forms elucidated by the SEDEX method were as follows: authigenic P (∼54–68 mg/kg; ∼41–46% TP) > extractable P (Ex-P; ∼36–53 mg/kg; ∼28–34%) > Fe-P (∼21–27 mg/kg; ∼13–19%) > OP (∼8.7–13 mg/kg; ∼5–8%) > detrital P (De-P; ∼2 mg/kg; ∼1–2% TP), with IP composed of ∼91–94% TP. These results showed that the SEDEX method elucidated higher concentrations of sedimentary P forms as well as the TP from these coastal sediments although the SMT method had the advantage of being more economic and faster. The results of both the SMT and SEDEX methods showed that the Andong salt marsh and Changjiang Estuary sediments had much bioavailable P. The mean percentages of bioavailable P from the SMT and SEDEX methods were ∼64–74% and 52–56% of TP, respectively, indicating that these sediments were prone to release P to the coastal areas.

A large number of mathematical models were developed for supporting agricultural production structure optimization decisions; however, few of them can address various uncertainties existing in many factors (e.g., eco-social benefit maximization, food security, employment stability and ecosystem balance). In this study, an interval-probabilistic agricultural production structure optimization model (IPAPSOM) is formulated for tackling uncertainty presented as discrete intervals and/or probability distribution. The developed model improves upon the existing probabilistic programming and inexact optimization approaches. The IPAPSOM considers not only food security policy constraints, but also involves rural households' income increase and eco-environmental conversation, which can effectively reflect various interrelations among different aspects in an agricultural production structure optimization system. Moreover, it can also help examine the reliability of satisfying (or risk of violating) system constraints under uncertainty. The model is applied to a real case of long-term agricultural production structure optimization in Dancheng County, which is located in Henan Province of Central China as one of the major grain producing areas. Interval solutions associated with different risk levels of constraint violation are obtained. The results are useful for generating a range of decision alternatives under various system benefit conditions, and thus helping decision makers to identify the desired agricultural production structure optimization strategy under uncertainty.

The asymmetric unit of the title compound, [Hg(C13H10N3O2)Cl]·H2O, contains two independent mercury(II) complexes with slightly different conformations, related via a pseudo-inversion centre, and two water molecules. The HgII atoms show a typical linear geometry to a C atom of the benzene ring and to a Cl atom. A benzene C and the azomethine N atom chelate the HgII atoms with weak intramolecular Hg...N bonding distances of 2.735 (3) and 2.739 (3) Å, respectively. The resulting five-membered metallacycles are nearly coplanar with the benzene rings [dihedral angles = 0.9 (1) and 0.7 (1)°], while the pyridine rings make dihedral angles with the benzene units of 58.17 (1) and 56.58 (1)°. In the crystal structure, the HgII complexes are linked by hydroxy donor and pyridine acceptor groups into chains along [010]. The water molecules connect the complexes through intermolecular O—H...Ocarbonyl bonds in the a-axis direction, and the azomethine H atoms donate towards the water O atoms, forming a three-dimensional network of intermolecular O—H...N, O—H...O and N—H...O hydrogen bonds.

The assembly and disassembly of ribonucleoproteins (RNPs) are dynamic processes that control every step of RNA metabolism, including mRNA stability. However, our knowledge of how RNP remodeling is achieved is largely limited to RNA helicase functions. Here, we report a previously unknown mechanism that implicates the ATPase p97, a protein-remodeling machine, in the dynamic regulation of mRNP disassembly. We found that p97 and its cofactor, UBXD8, destabilize p21, MKP-1, and SIRT1, three established mRNA targets of the RNA-binding protein HuR, by promoting release of HuR from mRNA. Importantly, ubiquitination of HuR with a short K29 chain serves as the signal for release. When cells are subjected to stress conditions, the steady-state levels of HuR ubiquitination change, suggesting a new mechanism through which HuR mediates the stress response. Our studies reveal a new paradigm in RNA biology: nondegradative ubiquitin signaling-dependent disassembly of mRNP promoted by the p97"UBXD8 complex to control mRNA stability. [ABSTRACT FROM AUTHOR]

A recent genome-wide bioinformatic analysis indicated that 54% of human genes undergo alternative polyadenylation. Although it is clear that differential selection of poly(A) sites can alter gene expression, resulting in significant biological consequences, the mechanisms that regulate polyadenylation are poorly understood. Here we report that the neuron-specific members of a family of RNA-binding proteins, Hu proteins, known to regulate mRNA stability and translation in the cytoplasm, play an important role in polyadenylation regulation. Hu proteins are homologs of the Drosophila embryonic lethal abnormal visual protein and contain three RNA recognition motifs. Using an in vitro polyadenylation assay with HeLa cell nuclear extract and recombinant Hu proteins, we have shown that Hu proteins selectively block both cleavage and poly(A) addition at sites containing U-rich sequences. Hu proteins have no effect on poly(A) sites that do not contain U-rich sequences or sites in which the U-rich sequences are mutated. All three RNA recognition motifs of Hu proteins are required for this activity. Overexpression of HuR in HeLa cells also blocks polyadenylation at a poly(A) signal that contains U-rich sequences. Hu proteins block the interaction between the polyadenylation cleavage stimulation factor 64-kDa subunit and RNA most likely through direct interaction with poly(A) cleavage stimulation factor 64-kDa subunit and cleavage and polyadenylation specificity factor 160-kDa subunit. These studies identify a novel group of mammalian polyadenylation regulators. Furthermore, they define a previously unknown nuclear function of Hu proteins. [ABSTRACT FROM AUTHOR]