Influenced phosphoproteins inrelated to DNA repair pathway under UV treatment.

<p>Diamond represents mismatch repair proteins, ellipse represents base excision repair proteins and rectangle stands for nucleotide excision repair proteins. The different colors represent different ratios of phosphorylation level from -2 to +2.</p

Mass spectrometry-based quantification of the cellular response to ultraviolet radiation in HeLa cells

<div><p>Ultraviolet (UV) irradiation is a common form of DNA damage that can cause pyrimidine dimers between DNA, which can cause gene mutations, even double-strand breaks and threaten genome stability. If DNA repair systems default their roles at this stage, the organism can be damaged and result in disease, especially cancer. To better understand the cellular response to this form of damage, we applied highly sensitive mass spectrometry to perform comparative proteomics of phosphorylation in HeLa cells. A total of 4367 phosphorylation sites in 2100 proteins were identified, many of which had not been reported previously. Comprehensive bioinformatics analysis revealed that these proteins were involved in many important biological processes, including signaling, localization and cell cycle regulation. The nuclear pore complex, which is very important for RNA transport, was changed significantly at phosphorylation level, indicating its important role in response to UV-induced cellular stress. Protein–protein interaction network analysis and DNA repair pathways crosstalk were also examined in this study. Proteins involved in base excision repair, nucleotide repair and mismatch repair changed their phosphorylation pattern in response to UV treatment, indicating the complexity of cellular events and the coordination of these pathways. These systematic analyses provided new clues of protein phosphorylation in response to specific DNA damage, which is very important for further investigation. And give macroscopic view on an overall phosphorylation situation under UV radiation.</p></div

Quantitative overview of phosphorylated peptides and proteins in <i>HeLa</i> cells following UV treatment.

<p>(A) Number of phosphorylated proteins and proteins’sites quantified in HeLa cells in response to UV treatment. (B) Distribution of identified phosphorylated peptides at Serine, Threonine and Tyrosine sites. (C) Distribution of phosphorylated and non-phosphorylated amino acids in secondary structure. (D) Comparison of phosphorylated peptides identified in this study (I) and Phospho.ELM database (II) (<a href="http://phospho.elm.eu.org/" target="_blank">http://phospho.elm.eu.org/</a>).Validation of phosphorylation sites in RPA1 (S38) and RFC3 (T76) by western blot. Plasmids with 3xFLAG-S38A or 3xFLAG-T76A mutation were transfected to HeLa cells and precipitated by M2 beads. The phosphorylation level between wildtype and mutant proteins were evaluated by western blotting using specific antibody.</p

Phosphorylation-specific motifs using the Motif-X algorithm.

<p>(A) Pro-directed motif centered on Thr and Ser with a strong preference for additional Pro residues C-terminal to the phosphate. (B) Double-phosphorylation motifs found in our study.</p

Network of phosphoproteins derived from data and the expanding view of phosphorylation level changes for parts of representative proteins.

<p>The different colors represent different ratios from -2 to +2. The highlight part are mismatch repair related protein—MSH6 network picture, DNA replication related protein—POLA1 and POLE network and nuclear pore complex protein—Nup153, Nup50, Nup188 and Nup214 network part.</p

Conization Using an Electrosurgical Knife for Cervical Intraepithelial Neoplasia and Microinvasive Carcinoma

<div><p>Objective</p><p>The aim of the present study was to evaluate the incidences of margin involvement, disease relapse, and complications in patients who had undergone conization using an electrosurgical knife (EKC) for cervical intraepithelial neoplasia (CIN) or microinvasive carcinomas (micro-CAs).</p><p>Materials and Methods</p><p>A retrospective case series analysis was performed with a total of 1359 patients who underwent EKC in Fudan University Shanghai Cancer Center between June 2004 and July 2010.</p><p>Results</p><p>The median age of the patients was 39 years old (range: 19-72). Conization revealed the presence of CIN in 1113 (81.9%) patients, micro-CA in 72 (5.3%) patients and invasive carcinomas in 44 (3.2%) patients. The remaining 130 (9.6%) patients were free of diseases in the cone specimens. Positive surgical margins, or endocervical curettages (ECCs) were found in 90 (7.6%) patients with CINs or micro-CAs. Three factors were associated with positive margins and ECCs and included age (>50 years; odds ratio (OR), 3.0, P<0.01), postmenopausal status (OR, 3.1, P<0.01) and microinvasive disease (OR, 2.7, P<0.01). One thousand and eighty-nine (92.0%) patients were followed-up regularly for a median follow-up duration of 46 months (range: 24-106 months). Disease relapse was documented in 50 (4.6%) patients. Eighty-two (6.0%) cases experienced surgical complications that needed to be addressed, including early or late hemorrhages, infections, cervical stenosis, etc.</p><p>Conclusions</p><p>Our patients demonstrated that EKC was an alternative technique for diagnosis and treatment of CIN or micro-CAs with relatively low rate of recurrence and acceptable rate of complications. A randomized clinical trial is warranted to compare EKC, CKC and LEEP in the management of CIN or micro-CA.</p></div

PCR and western analysis of transgenic T₀ plants.

<p>The fragment of 440bp from the T-DNA insert was amplified from genomic DNA isolated from different events of transgenic rice (A). The G6 expressed in transgenic rice plants were detected by its antiserum from rabbits (B). Lane 1 to 4, transgenic event R450-2, R450-5, R450-6 and R450-7, respectively; CK, non-transformed rice as the negative control; M, 100bp ladder (A) or 48 kDa pre-stained protein size maker (B).</p

New exploration of signal detection from the perspective of data mining: a pharmacovigilance analysis based on spontaneous reporting data in Zhenjiang, China

This study aimed to adopt the conventional signal detection methods to explore a new way of risk identification and to mine important drug risks from the perspective of big data based on Zhenjiang Adverse Event Reporting System (ZAERS). Data were extracted from ZAERS database between 2012 and 2022. The risks of all the reported drug event combinations were identified at the preferred term level and the standardized MedDRA query level using disproportionality analysis. Then, we conducted signal assessment according to the descriptions of drug labels. In total 41,473 ADE were reported and there were12 risky signals. Signal assessment indicates the suspected causal associations in clindamycin-taste and smell disorders, valsartan-hepatic enzyme increased and valsartan-edema peripheral; the specific manifestations of allergic reactions triggered by clindamycin, cefotaxime, cefazodime, ShexiangZhuanggu plaster, ShexiangZhuifeng plaster, and Yanhuning need to be refined in drug labels. In addition, the drug labels of NiuHuangShangQing tablet/capsule, Fuyanxiao capsule, and BiYanLing tablet should be improved. In this study, we attempted a new way to find potential drug risks using small spontaneous reporting data. Our findings also suggested the need for more precise identification of allergic risks and the improvement of traditional Chinese medicine labels.</p

Diagram of the T-DNA fragment of the binary plasmid pG6-450i for <i>Agrobacterium</i> transformation.

<p>ZmUbi-1, <i>Zea mays</i> polyubiquitin-1 promoter; CaMV35S, cauliflower mosaic virus 35S promoter; <i>G6</i>, the 5-enolpyruvylshikimate-3-phosphate synthase isolated from <i>Pseudomonas putida</i> fused with chloroplast transit peptide at the N-terminus (gb: EU169459); R450i, the inverted repeat sequence of the 207bp fragment of <i>CYP81A6</i>; LB and RB, left and right border of the T-DNA.</p

Design of Ti₃C₂T_<i>x</i>/SnO₂‑Selective Ethanolamine Sensor

Two-dimensional transition metal carbides/nitrides (MXenes) show great potential in volatile organic compound (VOC) sensors owing to their exceptional electrical properties, numerous active sites, and abundant terminal functional groups. However, pure MXene Ti3C2Tx is prone to oxidative degradation under ambient environment, and the insufficient response and poor stability are still grand challenges. Hereby, by deliberately introducing metal oxide semiconductor in multilayer Ti3C2Tx, a promising Ti3C2Tx/SnO2 sensor with excellent long-term stability and outstanding selectivity is developed for VOC monitoring. The research shows that the Ti3C2Tx/SnO2 hybrid sensor implements efficient detection of hydrogen-bonded gases and is especially highly efficient with ethanolamine (EA). The sensitivity of the hybrid sensor to EA is improved by over 10-fold in comparison with pristine Ti3C2Tx, besides the good selectivity to over 12 different VOCs. The synergistic effects of n-n nanoheterojunctions, the large specific surface area of 45.186 m2/g and mesoporous-rich hierarchical structure, and the functional terminal groups together facilitate the EA-sensitive properties. In addition, the innovative preparation of the Ti3C2Tx/SnO2 sensor, which takes advantage of terpinol, contributes to the close contact of Ti3C2Tx/SnO2 on the ceramic tubes, thus improving the sensor sensitivity. The scientific findings of this work may provide valuable ideas for the exploration of innovatively composite gas sensors