Universal relation between the conditional auto-correlation function and the cross-correlation function of biphotons.

We systematically studied the relation between the conditional auto-correlation function (CACF) and cross-correlation function (CCF) of biphotons or pairs of single photons. The biphotons were generated from a heated atomic vapor via the spontaneous four-wave mixing (SFWM) process. In practical usage, one single photon of a pair is utilized as the heralding photon, and another is employed as the heralded photon. Motivated by the data of CACF of the heralded photons versus CCF, we proposed a universal formula to predict the CACF. The derived formula was based on general theory and is also valid for the biphoton generation process of spontaneous parametric down-conversion (SPDC). With the formula, we utilized the experimentally determined parameters to predict CACFs, which can well agree with the measured CACFs. The proposed formula enables one to quantitatively know the CACF of heralded single photons without the measurement of Hanbury-Brown-Twiss-type three-fold coincidence count. This study provides a better understanding of biphoton generation using the SFWM or SPDC process. Our work demonstrates a valuable tool for analyzing a vital property of how the heralded photons are close to Fock-state single photons.

Hemoglobin loss method calculates blood loss during pancreaticoduodenectomy and predicts bleeding-related risk factors.

BACKGROUND: The common clinical method to evaluate blood loss during pancreaticoduodenectomy (PD) is visual inspection, but most scholars believe that this method is extremely subjective and inaccurate. Currently, there is no accurate, objective method to evaluate the amount of blood loss in PD patients. AIM: The hemoglobin (Hb) loss method was used to analyze the amount of blood loss during PD, which was compared with the blood loss estimated by traditional visual methods. The risk factors for bleeding were also predicted at the same time. METHODS: We retrospectively analyzed the clinical data of 341 patients who underwent PD in Shandong Provincial Hospital from March 2017 to February 2019. According to different surgical methods, they were divided into an open PD (OPD) group and a laparoscopic PD (LPD) group. The differences and correlations between the intraoperative estimation of blood loss (IEBL) obtained by visual inspection and the intraoperative calculation of blood loss (ICBL) obtained using the Hb loss method were analyzed. ICBL, IEBL and perioperative calculation of blood loss (PCBL) were compared between the two groups, and single-factor regression analysis was performed. RESULTS: There was no statistically significant difference in the preoperative general patient information between the two groups (P > 0.05). PD had an ICBL of 743.2 (393.0, 1173.1) mL and an IEBL of 100.0 (50.0, 300.0) mL (P < 0.001). There was also a certain correlation between the two (r = 0.312, P < 0.001). Single-factor analysis of ICBL showed that a history of diabetes [95% confidence interval (CI): 53.82-549.62; P = 0.017] was an independent risk factor for ICBL. In addition, the single-factor analysis of PCBL showed that body mass index (BMI) (95%CI: 0.62-76.75; P = 0.046) and preoperative total bilirubin > 200 µmol/L (95%CI: 7.09-644.26; P = 0.045) were independent risk factors for PCBL. The ICBLs of the LPD group and OPD group were 767.7 (435.4, 1249.0) mL and 663.8 (347.7, 1138.2) mL, respectively (P > 0.05). The IEBL of the LPD group 200.0 (50.0, 200.0) mL was slightly greater than that of the OPD group 100.0 (50.0, 300.0) mL (P > 0.05). PCBL was greater in the LPD group than the OPD group [1061.6 (612.3, 1632.3) mL vs 806.1 (375.9, 1347.6) mL] (P < 0.05). CONCLUSION: The ICBL in patients who underwent PD was greater than the IEBL, but there is a certain correlation between the two. The Hb loss method can be used to evaluate intraoperative blood loss. A history of diabetes, preoperative bilirubin > 200 µmol/L and high BMI increase the patient's risk of bleeding.

OTUB1 inhibits breast cancer by non-canonically stabilizing CCN6.

BACKGROUND: CCN6 is a matricellular protein that critically regulates the tumourigenesis and progression of breast cancer. Although the tumour-suppressive function of CCN6 has been extensively studied, molecular mechanisms regulating protein levels of CCN6 remain largely unclear. This study aims to investigate the regulation of CCN6 by ubiquitination and deubiquitinating enzymes (DUBs) in breast cancer. METHODS: A screening assay was performed to identify OTUB1 as the DUB for CCN6. Various biochemical methods were applied to elucidate the molecular mechanism of OTUB1 in the regulation of CCN6. The role of OTUB1-CCN6 interaction in breast cancer was studied with cell experiments and the allograft model. The correlation of OTUB1 and CCN6 in human breast cancer was determined by immunohistochemistry and Western blot. RESULTS: We found that CCN6 protein levels were controlled by the ubiquitin-proteasome system. The K48 ubiquitination and degradation of CCN6 was inhibited by OTUB1, which directly interacted with CCN6 through its linker domain. Furthermore, OTUB1 inhibited the ubiquitination of CCN6 in a non-canonical manner. Deletion of OTUB1, concomitant with reduced CCN6 abundance, increased the migration, proliferation and viability of breast cancer cells. Supplementation of CCN6 abolished the effect of OTUB1 deletion on breast cancer. Importantly, OTUB1 expression was downregulated in human breast cancer and positively correlated with CCN6 levels. CONCLUSION: This study identified OTUB1 as a novel regulator of CCN6 in breast cancer.

Glycosyltransferase GLT8D1 and GLT8D2 serve as potential prognostic biomarkers correlated with Tumor Immunity in Gastric Cancer.

BACKGROUND: Glycosylation involved in various biological function, aberrant glycosylation plays an important role in cancer development and progression. Glycosyltransferase 8 domain containing 1 (GLT8D1) and GLT8D2, as members of the glycosyltransferase family proteins, are associated with transferase activity. However, the association between GLT8D1/2 and gastric cancer (GC) remains unclear. We aimed to investigate the potential prognostic value and oncogenic role of GLT8D1/2 in GC. METHODS: The relationship between GLT8D1/2 and GC was evaluated through comprehensive bioinformatics approaches. A series of factors like gene expression patterns, Kaplan-Meier survival analyses, Cox regression analyses, prognostic nomogram, calibration curves, ROC curves, function enrichment analyses, tumor immunity association, genetic alterations, and DNA methylation were included. Data and statistical analyses were performed using R software (v3.6.3). RESULTS: Both GLT8D1 and GLT8D2 expression were significantly upregulated in GC tissues(n = 414) compared with normal tissues(n = 210), and high expression of GLT8D1/2 was remarkably correlated with poor prognosis for GC patients. Cox regression analyses implied that GLT8D1/2 could act as independent prognostic factors in GC. Furthermore, gene function analyses indicated that multiple signaling pathways involving tumor oncogenesis and development enriched, such as mTOR, cell cycle, MAPK, Notch, Hedgehog, FGF, and PI3K-Akt signaling pathways. Moreover, GLT8D1/2 was significantly associated with immune cell infiltration, immune checkpoint genes, and immune regulators TMB/MSI. CONCLUSION: GLT8D1/2 may serve as potential prognostic markers of poor prognosis in GC correlated with tumor immunity. The study provided an insight into identifying potential biomarkers and targets for prognosis, immunotherapy response, and therapy in GC.

Selective Removal of Emerging Organic Contaminants from Water Using Electrogenerated Fe(IV) and Fe(V) under Near-Neutral Conditions.

Fe(IV) and Fe(V) are promising oxidants for the selective removal of emerging organic contaminants (EOCs) from water under near-neutral conditions. The Fe(III)-assisted electrochemical oxidation system with a BDD anode (Fe(III)-EOS-BDD system) has been employed to generate Fe(VI), while the generation and contributions of Fe(IV) and Fe(V) have been largely ignored. Thus, we examined the feasibility and involved mechanisms of the selective degradation of EOCs in the Fe(III)-EOS-BDD system under near-neutral conditions. It was found that Fe(III) application selectively accelerated the electro-oxidation of phenolic and sulfonamide organics and made the oxidation system be resistant to interference from Cl-, HCO3-, and humic acid. Several lines of evidence indicated that EOCs were decomposed via direct electron-transfer process on the BDD anode and by Fe(IV) and Fe(V) but not Fe(VI), besides HO•. Fe(VI) was not generated until the exhaustion of EOCs. Furthermore, the overall contributions of Fe(IV) and Fe(V) to the oxidation of phenolic and sulfonamide organics were over 45%. Our results also revealed that Fe(III) was oxidized primarily by HO• to Fe(IV) and Fe(V) in the Fe(III)-EOS-BDD system. This study advances the understanding of the roles of Fe(IV) and Fe(V) in the Fe(III)-EOS-BDD system and provides an alternative for utilizing Fe(IV) and Fe(V) under near-neutral conditions.

USP25 inhibits renal fibrosis by regulating TGFß-SMAD signaling pathway in Ang II-induced hypertensive mice.

Renal fibrosis is a crucial pathological feature of hypertensive renal disease (HRD). In-depth analysis of the pathogenesis of fibrosis is of great significance for the development of new drugs for the treatment of HRD. USP25 is a deubiquitinase that can regulate the progression of many diseases, but its function in the kidney remains unclear. We found that USP25 was significantly increased in human and mice HRD kidney tissues. In the HRD model induced by Ang II, USP25-/- mice showed significant aggravation of renal dysfunction and fibrosis compared with the control mice. Consistently, AAV9-mediated overexpression of USP25 significantly improved renal dysfunction and fibrosis. Mechanistically, USP25 inhibited the TGF-ß pathway by reducing SMAD4 K63-linked polyubiquitination, thereby suppressing SMAD2 nuclear translocation. In conclusion, this study demonstrates for the first time that the deubiquitinase USP25 plays an important regulatory role in HRD.

Luminescence Enhancement and Temperature Sensing Properties of Hybrid Bismuth Halides Achieved via Tuning Organic Cations.

Bismuth-halide-based inorganic-organic hybrid materials (Bi-IOHMs) are desirable in luminescence-related applications due to their advantages such as low toxicity and chemical stability. Herein, two Bi-IOHMs of [Bpy][BiCl4(Phen)] (1, Bpy = N-butylpyridinium, Phen = 1,10-phenanthroline) and [PP14][BiCl4(Phen)]·0.25H2O (2, PP14 = N-butyl-N-methylpiperidinium), containing different ionic liquid cations and same anionic units, have been synthesized and characterized. Single-crystal X-ray diffraction reveals that compounds 1 and 2 crystallize in the monoclinic space group of P21/c and P21, respectively. They both possess zero-dimensional ionic structures and exhibit phosphorescence at room temperature upon excitation of UV light (375 nm for 1, 390 nm for 2), with microsecond lifetime (24.13 µs for 1 and 95.37 µs for 2). Hirshfeld surface analysis has been utilized to visually exhibit the different packing motifs and intermolecular interactions in 1 and 2. The variation in ionic liquids makes compound 2 have a more rigid supramolecular structure than 1, resulting in a significant enhancement in photoluminescence quantum yield (PLQY), that is, 0.68% for 1 and 33.24% for 2. In addition, the ratio of the emission intensities for compounds 1 and 2 shows a correlation with temperature. This work provides new insight into luminescence enhancement and temperature sensing applications involving Bi-IOHMs.

Discovery of alantolactone as a naturally occurring NLRP3 inhibitor to alleviate NLRP3-driven inflammatory diseases in mice.

BACKGROUND AND PURPOSE: The NLR family pyrin domain-containing 3 (NLRP3) inflammasome is activated in many inflammatory conditions. So far, no low MW compounds inhibiting NLRP3 have entered clinical use. Identification of naturally occurring NLRP3 inhibitors may be beneficial to the design and development of compounds targeting NLRP3. Alantolactone is a phytochemical from a traditional Chinese medicinal plant with anti-inflammatory activity, but its precise target remains unclear. EXPERIMENTAL APPROACH: A bank of phytochemicals was screened for inhibitors of NLRP3-driven production of IL-1ß in cultures of bone-marrow-derived macrophages from female C57BL/6 mice. Models of gouty arthritis and acute lung injury in male C57BL/6J mice were used to determine the in vivo effects of the most potent compound. KEY RESULTS: Among the 150 compounds screened in vitro, alantolactone exhibited the highest inhibitory activity against LPS + ATP-induced production of IL-1ß in macrophages, suppressing IL-1ß secretion, caspase-1 activation and pyroptosis. Alantolactone directly bound to the NACHT domain of NLRP3 to inhibit activation and assembly of NLRP3 inflammasomes. Molecular simulation analysis suggested that Arg335 in NLRP3 was a critical residue for alantolactone binding, leading to suppression of NLRP3-NEK7 interaction. In vivo studies confirmed significant alleviation by alantolactone of two NLRP3-driven inflammatory conditions, acute lung injury and gouty arthritis. CONCLUSION AND IMPLICATIONS: The phytochemical alantolactone inhibited activity of NLRP3 inflammasomes by directly targeting the NACHT domain of NLRP3. Alantolactone shows great potential in the treatment of NLRP3-driven diseases and could lead to the development of novel NLRP3 inhibitors.

Preparation of novel trivalent vaccine against enterotoxigenic Escherichia coli for preventing newborn piglet diarrhea.

OBJECTIVE: To develop a trivalent genetically engineered inactivated Escherichia coli vaccine (K88ac-3STa-LTB) that neutralizes the STa toxin by targeting fimbriae and entertoxins for the treatment of enterotoxigenic E coli. ANIMALS: 18- to 22-g mice, rabbits, pregnant sows. PROCEDURES: Using PCR, the K88ac gene and LTB gene were cloned separately from the template C83902 plasmid. At the same time, the 3 STa mutant genes were also amplified by using the gene-directed mutation technology. Immune protection experiments were performed, and the minimum immune dose was determined in mice and pregnant sows. RESULTS: The ELISA test could be recognized by the STa, LTB, and K88ac antibodies. Intragastric administration in the suckling mouse confirmed that the protein had lost the toxicity of the natural STa enterotoxin. The results of the immune experiments showed that K88ac-3STa-LTB protein could stimulate rabbits to produce serum antibodies and neutralize the toxicity of natural STa enterotoxin. The efficacy test of the K88ac-3STa-LTB-inactivated vaccine showed that the immune protection rate of the newborn piglets could reach 85% on the first day after suckling. At the same time, it was determined that the minimum immunization doses for mice and pregnant sows were 0.2 and 2.5 mL, respectively. CLINICAL RELEVANCE: This research indicates that the K88ac-3STa-LTB trivalent genetically engineered inactivated vaccine provides a broad immune spectrum for E coli diarrhea in newborn piglets and prepares a new genetically engineered vaccine candidate strain for prevention of E coli diarrhea in piglets.

Development of a new candidate vaccine against piglet diarrhea caused by Escherichia coli.

Enterotoxigenic Escherichia coli (ETEC) is an important type of pathogenic bacteria that causes diarrhea in humans and young livestock. The pathogen has a high morbidity and mortality rate, resulting in significant economic losses in the pig industry. To effectively prevent piglet diarrhea, we developed a new tetravalent genetically engineered vaccine that specifically targets ETEC. To eliminate the natural toxin activity of ST1 enterotoxin and enhance the preventive effect of the vaccine, the mutated ST 1, K88ac, K99, and LT B genes were amplified by PCR and site-specific mutation techniques. The recombinant strain BL21(DE3)(pXKK3SL) was constructed and achieved high expression. Animal experiments showed that the inactivated vaccine had eliminated the natural toxin activity of ST1. The immune protection test demonstrated that the inclusion body and inactivated vaccine exhibited a positive immune effect. The protection rates of the inclusion body group and inactivated vaccine group were 96 and 98%, respectively, when challenged with 1 minimum lethal dose, indicating that the constructed K88ac-K99-3ST1-LTB vaccine achieved a strong immune effect. Additionally, the minimum immune doses for mice and pregnant sows were determined to be 0.2 and 2 mL, respectively. This study suggests that the novel K88ac-K99-3ST1-LTB vaccine has a wide immune spectrum and can prevent diarrhea caused by ETEC through enterotoxin and fimbrial pathways. The aforementioned research demonstrates that the K88ac-K99-3ST1-LTB vaccine offers a new genetically engineered vaccine that shows potential for preventing diarrhea in newborn piglets.

The efficacy of vonoprazan combined with different dose amoxicillin on eradication of Helicobacter pylori: an open, multicenter, randomized clinical study.

Background: The use of vonoprazan (VPZ) has improved the Helicobacter pylori (H. pylori) eradication therapy in Japan. There is no agreement on the dosage and frequency of amoxicillin administration in the VPZ dual treatment in China. We aimed to investigate the clinical effectiveness and safety of 3 treatment regimens using VPZ as an acid-suppressing medication to eradicate H. pylori. Methods: This experiment involved an open, multicenter, randomized, and parallel controlled clinical investigation. A total of 230 newly diagnosed H. pylori-infected patients were then randomly assigned to 1 of 3 groups: (I) H-VA (high-dose amoxicillin combined with VPZ): VPZ 20 mg b.i.d with amoxicillin 750 mg q.i.d for 7 days; (II) L-VA (low-dose amoxicillin combined with VPZ): VPZ 20 mg b.i.d plus amoxicillin 500 mg q.i.d for 7 days; (III) VAC (amoxicillin combined with VPZ and clarithromycin): VPZ 20 mg b.i.d plus amoxicillin 750 mg plus clarithromycin 500 mg for 7 days. At least 4 weeks after treatment, the urea breath test (UBT) was reexamined. The effectiveness of various regimens was assessed based on compliance, safety, and eradication rate. Results: The regimen effectiveness was 63.5% (54/85) in the H-VA group, 58.3% (49/84) in the L-VA group, and 60.7% (37/61) in the VAC group, according to intention to treat (ITT) analysis. According to per protocol (PP) analysis, the eradication rate of the H-VA group was 65.1% (54/83), that of the L-VA group was 66.2% (49/74), and that of the VAC group was 64.9% (37/57). There was no discernible difference in the eradication rate across the 3 regimens, as shown by the results of ITT analysis (χ2=0.032, P=0.984) and PP analysis (χ2=0.480, P=0.786). The rate of adverse effect was 16.90% in the H-VA group, 13.20% in the L-VA group, and 24.10% in the VAC group. There was no discernible difference in the incidence of adverse effect between the three groups (χ2=2.784, P=0.266). Conclusions: None of the 7-day elimination regimens investigated in this study, which included the acid-suppressing medicine VPZ and either a dual treatment paired with amoxicillin, or a triple treatment combined with amoxicillin and clarithromycin, achieved an acceptable eradication rate of H. pylori. Further research is required to identify an effective and safe treatment regimen. Trial Registration: Chinese Clinical Trial Registry identifier: ChiCTR2000040955.

Fate and transformation of iodine species during Mn(VII)/sulfite treatment in iodide-containing water.

During oxidative treatment of iodide (I- )-containing waters, I- is easy to be oxidized into hypoiodous acid (HOI) by various oxidants and the further reaction of HOI with organic compounds can lead to the formation of iodinated disinfection by-products (I-DBPs). Oxidation of HOI to iodate (IO3 - ) or reduction of HOI to I- has been proposed to reduce the formation of I-DBPs. Because the reaction of HOI with sulfite proceeds rapidly, this study examined the fate of iodine and the formation of I-DBPs in Mn(VII)/sulfite process. Results showed that I- was oxidized to HOI but the further formation of IO3 - was suppressed due to the fast reduction of HOI to I- by sulfite. The reactions of HOI with SO3 2- and IO- with SO3 2- are the major pathways with species-specific second-order rate constants determined to be 1.12 × 105 M-1 s-1 and 9.43 × 107 M-1 s-1 , respectively. The rapid reaction of HOI with sulfite plays an essential role in minimizing the formation of iodinated products in HOI- and phenol-containing solutions. The toxic risk analysis showed that the toxicity of the generated DBPs from Mn(VII)/sulfite pre-oxidation followed by chlorination only changed slightly. PRACTITIONER POINTS: The decay of I- was negligible in Mn(VII)/sulfite process. The rapid reaction of HOI with SO3 2- resulted in the negligible generation of IO3 - . Mn(VII)/sulfite process exerted slight influence on the formation of I-DBPs. Mn(VII)/sulfite process is promising for the pretreatment of I- -containing water.

Boosting the oxidative capacity of the Fe(0)/O2 system via an air-breathing cathode.

The corrosion of Fe(0) in the presence of O2 in nature can lead to the oxidation of organic compounds, but the efficiency is very limited. Herein, attempts were made to establish a galvanic system that separates the anodic Fe(0) oxidation reaction and the cathodic O2 reduction reaction using an air-breathing cathode. Compared with the chemical Fe(0)/O2 system, it exhibited a substantially higher capability of destroying a variety of pollutants, such as organic dyes (12 types), phenol, nitrobenzene, acetaminophen, phenol, and ethylenediaminetetraacetic acid. The degradation rate constant of a model dye (i.e., Rhodamine B) increased from 0.047 min-1 (chemical) to 1.412 min-1 (galvanic) under the passive air-breathing condition. The electric circuit design promoted Fe(0) dissolution to Fe(II) and triggered electron transfer that drives O2 reduction to H2O2, two important species responsible for the generation of HO• at high abundance. In addition, the galvanic Fe(0)/O2 system produces electricity while destroying pollutants. Tests with real Ni plating wastewater further demonstrated the capability of the system to oxidize complexed organics and phosphite. This study provides a new strategy for boosting the oxidative capacity of the Fe(0)/O2 system, which shows promise for acid wastewater treatment.

FAK mediates LPS-induced inflammatory lung injury through interacting TAK1 and activating TAK1-NFκB pathway.

Acute lung injury (ALI), characterized by inflammatory damage, is a major clinical challenge. Developing specific treatment options for ALI requires the identification of novel targetable signaling pathways. Recent studies reported that endotoxin lipopolysaccharide (LPS) induced a TLR4-dependent activation of focal adhesion kinase (FAK) in colorectal adenocarcinoma cells, suggesting that FAK may be involved in LPS-induced inflammatory responses. Here, we investigated the involvement and mechanism of FAK in mediating LPS-induced inflammation and ALI. We show that LPS phosphorylates FAK in macrophages. Either FAK inhibitor, site-directly mutation, or siRNA knockdown of FAK significantly suppresses LPS-induced inflammatory cytokine production in macrophages. FAK inhibition also blocked LPS-induced activation of MAPKs and NFκB. Mechanistically, we demonstrate that activated FAK directly interacts with transforming growth factor-ß-activated kinase-1 (TAK1), an upstream kinase of MAPKs and NFκB, and then phosphorylates TAK1 at Ser412. In a mouse model of LPS-induced ALI, pharmacological inhibition of FAK suppressed FAK/TAK activation and inflammatory response in lung tissues. These activities resulted in the preservation of lung tissues in LPS-challenged mice and increased survival during LPS-induced septic shock. Collectively, our results illustrate a novel FAK-TAK1-NFκB signaling axis in LPS-induced inflammation and ALI, and support FAK as a potential target for the treatment of ALI.

Oolong Tea Consumption and the Risk of Oral Squamous Cell Carcinoma: A Propensity Score-Based Analysis in Southeast China.

Oolong tea is one of the world's most popular non-alcoholic beverages, particularly in coastal Southeast China. Hitherto, epidemiological studies on the association between oolong tea consumption and the risk of patients with oral squamous cell carcinoma (OSCC) are very limited. This study aimed to evaluate the potential effect of oolong tea consumption on OSCC risk in Southeast China. From January 2010 to October 2020, face-to-face interviews were conducted for 744 newly diagnosed OSCC patients and 1,029 healthy controls to collect information on demographics, oolong tea consumption behaviors, and other lifestyle factors. Propensity score matching (PSM), inverse probability of treatment weight (IPTW), and stabilized inverse probability of treatment weight (SIPTW) were utilized to minimize confounding effects. Multivariate, conditional, and weighted logistic regression was used to evaluate the associations of oolong tea consumption behaviors with OSCC risk. Participants who drank oolong tea showed a lower risk of OSCC when compared to their non-drink counterparts [PSM population, OR (95%CI): 0.69 (0.49-0.97); SIPTW population, OR (95%CI): 0.74 (0.58-0.94)]. Moreover, the reduced risk was found to be significantly associated with certain tea-drinking habits (consumed amount over 500 mL per day, a duration of <20 years, age at initiation older than 30 years, and warm and moderately concentrated tea). Similar results were yielded in the sensitivity analyses (Multivariate adjustment and the IPTW analysis). Furthermore, subgroup analysis revealed that the negative association of oolong tea drinking with OSCC risk was more evident among those with poor oral hygiene. This study provides supportive evidence that oolong tea consumption may have a potentially beneficial effect in preventing OSCC, especially for those with poor oral hygiene.

Isolation, structure elucidation, and high-performance liquid chromatography quantification of photolytic degradation impurities in acrivastine.

Acrivastine is a second-generation H1-receptor antagonist, and its structure is sensitive to ultraviolet. Four unknown and one reported degradation products can be detected in the ultraviolet radiation solutions of acrivastine. To improve the quality control of acrivastine, the photodegradation impurities were isolated and structurally elucidated. There are four new impurities (1-3 and 5), and one reported compound (4). The isolation strategy was designed as preparative high-performance liquid chromatography using a reversed phase column with volatile acid addition in the mobile phase, combined with preparative thin-layer chromatography using silica gel with alkaline addition in the mobile phase. Using the developed methods, five impurities (1-5) were efficiently purified after two or three chromatography runs with purities > 95%. The structures of compounds 1-5 are elucidated based on spectroscopy analysis of MS, and nuclear magnetic resonance spectroscopy. Using the impurity standard, the high-performance liquid chromatography method was developed and validated. The method was proved to be sensitive, accurate (Recovery% 96.1-107.7%), linear (0.15-0.75 µg/mL, R2 > 0.996), robust, and specific, and it was successfully used to determine the degradation impurities of acrivastine and its formulation.

MicroRNA-148a-3p suppresses cell proliferation and migration of esophageal carcinoma by targeting CEP55.

This study evaluated microRNA-148a-3p in esophageal carcinoma cells. The prediction of bioinformatics analysis revealed that microRNA-148a-3p may target CEP55. qRT-PCR and western blot showed that CEP55 level in esophageal carcinoma cells and tissue was dramatically higher than that of normal cells and tissue, while microRNA-148a-3p was the opposite. Forced expression of microRNA-148a-3p restrained cell malignant behaviors of esophageal carcinoma, and repression of microRNA-148a-3p resulted in the converse results in terms of cell function. Dual-luciferase assay confirmed that microRNA-148a-3p targeted CEP55. CEP55 attenuated the suppressive effect of microRNA-148a-3p on proliferation and migration of esophageal carcinoma cells, demonstrating that microRNA-148a-3p regulated function of esophageal carcinoma cells via decreasing CEP55 level. Microscopy observation indicated that cell morphology was also affected by the microRNA-148a-3p/CEP55 axis. Furthermore, western blot analysis revealed that the PI3K/AKT signaling pathway could be suppressed by activating the microRNA-148a-3p/CEP55 axis. Finally, in vivo experiments confirmed the effects of microRNA-148a-3p on tumorigenesis. Thus, microRNA-148a-3p could act as a repressor in esophageal carcinoma via binding to CEP55.

Optimal Size Criterion for Malignant Lymph Nodes and a Novel Lymph Node Clinical Staging System for Unresectable Esophageal Squamous Cell Carcinoma: Evaluation by Multislice Spiral Computed Tomography.

Objectives: The current Chinese draft nodal clinical staging system for unresectable esophageal cancer is controversial. Our study aimed to propose a new diagnostic criterion for lymph node metastasis (LNM) detected by multislice spiral computed tomography (MSCT) in nonsurgically treated esophageal squamous cell carcinoma (ESCC) patients and then develop a novel lymph node (LN) clinical staging system for better individual prognostic prediction. Methods: The short-axis diameters of regional LNs were measured in 393 nonsurgical patients. Regional nodes were considered positive for malignancy if the nodal size exceeded the optimal size, which was determined by Kaplan-Meier survival analysis. The novel LN clinical staging system was then constructed using the LASSO model based on the relative prognostic importance of different LN stations. Validation cohort was included to confirm the prognostic performance. Results: Regional nodes were considered positive for malignancy if they were larger than 10 mm in the low cervical and upper thoracic segments, 7 mm in the middle thoracic segment, and 8 mm in the lower thoracic and celiac segments. Using the LASSO model, stations 2R, 3A, 7 and 16 were qualified in the model. Further analysis showed that our LN clinical staging system had better homogeneity, discriminatory ability and clinical value than the draft nodal staging system. Conclusions: Our results show that the new diagnostic criterion may improve the diagnostic value of MSCT in metastatic LNs. The novel LN clinical staging system can stratify nonsurgically treated ESCC patients into different risk groups, providing valuable information for decision making and outcome prediction.

Evidence Mapping of Proton Therapy, Heavy Ion Therapy, and Helical Tomotherapy for Gastric Cancer.

PURPOSE: This study aimed to systematically present application situation and therapeutic effect of proton therapy (PT), heavy ion therapy, and helical tomotherapy (TOMO) for gastric cancer (GC), and to find gaps of existing studies. METHODS: PubMed, EMBASE, the Cochrane Library, Web of Science, and Chinese Biological Medical Database were searched. Tables, bubble plot, and heat map were conducted to display results. RESULTS: Fourteen studies were included. About PT, 7 single-arm studies showed median overall survival (OS) within 2-66 months and 1 study reported 40% of patients happened moderate degree of radiation gastritis. About TOMO, 1 study reported longer median OS and progression-free survival, lower occurrence of Grade III toxicity, and late toxicity compared to 3D-CRT, while another study remained neutral. About heavy ion therapy, there was no clinical study was found. CONCLUSIONS: Existing studies presented good clinic treatment effect about PT and TOMO for GC, and furthermore clinical studies are needed.