HBV PreC interacts with SUV39H1 to induce viral replication by blocking the proteasomal degradation of viral polymerase.

Hepatitis B e antigen (HBeAg) seropositivity during the natural history of chronic hepatitis B (CHB) is known to coincide with significant increases in serum and intrahepatic HBV DNA levels. However, the precise underlying mechanism remains unclear. In this study, we found that PreC (HBeAg precursor) genetic ablation leads to reduced viral replication both in vitro and in vivo. Furthermore, PreC impedes the proteasomal degradation of HBV polymerase, promoting viral replication. We discovered that PreC interacts with SUV39H1, a histone methyltransferase, resulting in a reduction in the expression of Cdt2, an adaptor protein of CRL4 E3 ligase targeting HBV polymerase. SUV39H1 induces H3K9 trimethylation of the Cdt2 promoter in a PreC-induced manner. CRISPR-mediated knockout of endogenous SUV39H1 or pharmaceutical inhibition of SUV39H1 decreases HBV loads in the mouse liver. Additionally, genetic depletion of Cdt2 in the mouse liver abrogates PreC-related HBV replication. Interestingly, a negative correlation of intrahepatic Cdt2 with serum HBeAg and HBV DNA load was observed in CHB patient samples. Our study thus sheds light on the mechanistic role of PreC in inducing HBV replication and identifies potential therapeutic targets for HBV treatment.

Salidroside promotes angiogenesis after cerebral ischemia in mice through Shh signaling pathway.

AIMS: The purpose of this study was to explore the impacts of salidroside on vascular regeneration, vascular structural changes and long-term neurological recuperation following cerebral ischemia and its possible mechanism. MAIN METHODS: From Day 1 to Day 28, young male mice with middle cerebral artery blockage received daily doses of salidroside and measured neurological deficits. On the 7th day after stroke, the volume of cerebral infarction was determined using TTC and HE staining. Microvascular density, astrocyte coverage, angiogenesis and the expression of the Shh signaling pathway were detected by IF, qRTPCR and WB at 7, 14 and 28 days after stroke. Changes in blood flow, blood vessel density and diameter from stroke to 28 days were measured by the LSCI and TPMI. KEY FINDINGS: Compared with the dMACO group, the salidroside treatment group significantly promoted the recovery of neurological function. Salidroside was found to enhance cerebral blood flow perfusion and reduce the infarct on the 7th day after stroke. From the 7th to the 28th day after stroke, salidroside treatment boosted the expression of CD31, CD31+/BrdU+, and GFAP in the cortex around the infarction site. On the 14th day after stroke, salidroside significantly enhanced the width and density of blood vessels. Salidroside increased the expression of histones and genes in the Shh signaling pathway during treatment, and this effect was weakened by the Shh inhibitor Cyclopamine. SIGNIFICANCE: Salidroside can restore nerve function, improve cerebral blood flow, reduce cerebral infarction volume, increase microvessel density and promote angiogenesis via the Shh signaling pathway.

Alkoxycarbonyl Groups in Metalloesters Showing Oxocarbenium-like Structure and Alkylating Reactivity.

In contrast to the well-documented acylating reactivity, the alkylating reactivity of the alkoxycarbonyl group, as signified by its oxocarbenium-like resonance structure, remains almost unexplored. Herein, the first series of Co/Ni dinuclear metalloesters exhibiting the novel oxocarbenium-like alkoxycarbonyl groups were synthesized and characterized. In these deformed alkoxycarbonyl groups, the Ccarbonyl-Oalkoxyl bonds were contracted to 1.177(11)~1.191(9) Šwith the elongations of the Ccarbonyl=Ocarbonyl bonds to 1.368(13)~1.441(9) Å. Meanwhile, the O-Calkyl bonds were also elongated to 1.522(11) ~1.607(15) Å, and were by far the longest O-Calkyl bonds reported for alkoxycarbonyl groups. As triggered by the long O-Calkyl distances, the alkylating reactivity of the oxocarbenium-like methoxycarbonyl group towards a series of C/N/O-nucleophiles via the rare BAL2 mechanism at ambient conditions was examined. Furthermore, the homo-etherifications of alcohols mediated by the Co/Ni dinuclear metalloesters were investigated. The yields followed the trend ethanol≫n-propanol≫n-butanol ≈n-pentanol, that closely related to the structure features of the alkoxycarbonyl groups in corresponding metalloesters: while the ethoxycarbonyl group showed the reactive oxocarbenium-like framework, the n-propoxycarbonyl group displayed the dioxocarbenium-like skeleton with a shorter O-Calkyl bond; In comparison, the classical frameworks with unactivated alkyl moieties were observed for n-butoxycarbonyl and n-pentoxycarbonyl groups.

Synthetic 5-amino-6-D-ribitylaminouracil paired with inflammatory stimuli facilitates MAIT cell expansion in vivo.

Introduction: Mucosal-associated invariant T (MAIT) cells are a population of innate-like T cells, which mediate host immunity to microbial infection by recognizing metabolite antigens derived from microbial riboflavin synthesis presented by the MHC-I-related protein 1 (MR1). Namely, the potent MAIT cell antigens, 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil (5-OP-RU) and 5-(2-oxoethylideneamino)-6-D-ribitylaminouracil (5-OE-RU), form via the condensation of the riboflavin precursor 5-amino-6-D-ribitylaminouracil (5-A-RU) with the reactive carbonyl species (RCS) methylglyoxal (MG) and glyoxal (G), respectively. Although MAIT cells are abundant in humans, they are rare in mice, and increasing their abundance using expansion protocols with antigen and adjuvant has been shown to facilitate their study in mouse models of infection and disease. Methods: Here, we outline three methods to increase the abundance of MAIT cells in C57BL/6 mice using a combination of inflammatory stimuli, 5-A-RU and MG. Results: Our data demonstrate that the administration of synthetic 5-A-RU in combination with one of three different inflammatory stimuli is sufficient to increase the frequency and absolute numbers of MAIT cells in C57BL/6 mice. The resultant boosted MAIT cells are functional and can provide protection against a lethal infection of Legionella longbeachae. Conclusion: These results provide alternative methods for expanding MAIT cells with high doses of commercially available 5-A-RU (± MG) in the presence of various danger signals.

Direct synthesis of oxalic acid via oxidative CO coupling mediated by a dinuclear hydroxycarbonylcobalt(III) complex.

Oxidative coupling of CO is a straightforward and economic benign synthetic route for value-added α-diketone moiety containing C2 or higher carbon compounds in both laboratory and industry, but is still undeveloped to date. In this work, a rare coplanar dinuclear hydroxycarbonylcobalt(III) complex, bearing a Schiff-base macrocyclic equatorial ligand and a µ-κ1(O):κ1(O')-acetate bridging axial ligand, is synthesized and characterized. The Co(III)-COOH bonds in this complex can be feasibly photocleaved, leading to the formation of oxalic acid. Moreover, the light-promoted catalytic direct production of oxalic acid from CO and H2O using O2 as the oxidant with good selectivity (> 95%) and atom economy at ambient temperature and gas pressure based on this dicobalt(III) complex have been achieved, with a turnover number of 38.5. The 13C-labelling and 18O-labelling experiments confirm that CO and H2O act as the sources of the -COOH groups in the dinuclear hydroxycarbonylcobalt(III) complex and the oxalic acid product.

C-H bond activations by the HO˙/(Salophent-Bu)Co(II) radical pair generated via homolysis of a terminal Co(III)-OH bond.

The reactive HO˙/(Salophent-Bu)Co(II) radical pair was observed to be generated via homolysis of the terminal Co(III)-OH bond in transient (Salophent-Bu)(L)Co(III)(OH) (L = Py, MeOH) complexes as indicated by UV-Vis and EPR measurements. Based on this elementary process, C-H bond activations in acetone, 2-butanone, acetonitrile and benzene were achieved under ambient conditions. For the reactions of the first three substrates, the alkylcobalt(III) complexes were formed as the products.

Assessment of neutrophil to lymphocyte ratio, C-reactive protein, mean platelet volume in obese, and nonobese patients with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is associated with low-grade chronic inflammation. This was a retrospective case-control study. In the present study, the risk coefficients of neutrophil to lymphocyte ratio (NLR), high-sensitive C-reactive protein (hs-CRP), and mean platelet volume (MPV) in obese patients with PCOS were determined. This study was designed to investigate NLR, hs-CRP, and MPV levels in 68 obese patients with PCOS and 44 nonobese patients with PCOS, and our study group was matched with 47 obese and 43 nonobese controls, respectively. PCOS group had higher MPV, NLR, insulin, glucose, and HOMA-IR rates than those of the controls. Subgroup analyses revealed that the obese PCOS group had higher NLR, hs-CRP, and MPV levels compared to those of controls. The obese PCOS group had higher NLR, hs-CRP, and MPV levels compared to those of the nonobese PCOS group. The odds ratios and 95% confidence intervals of those variables (NLR, hs-CRP, MPV) were found significant (P < .05). NLR, hs-CRP, and MPV variables were found statistically significant in the analysis of receiver operating characteristics. Our study demonstrated that NLR, hs-CRP, and MPV levels are increased in patients with obese PCOS.

Transition Metal Free Stannylation of Alkyl Halides: The Rapid Synthesis of Alkyltrimethylstannanes.

A transition metal free stannylation reaction of alkyl bromides and iodides with hexamethyldistannane has been developed. This protocol is operationally convenient and features a rapid reaction and good functional group tolerance. A wide range of functionalized primary and secondary alkyl and benzyl trimethyl stannanes are prepared in moderate to excellent yields. The success of the gram-scale procedure and tandem Stille coupling reaction has allowed this protocol to demonstrate potential for application in organic synthesis. Both experimental and theoretical studies reveal the mechanistic details of this stannylation reaction.

Isolated fallopian tube torsion with paraovarian cysts: a case report and literature review.

BACKGROUND: Isolated fallopian tube torsion (IFTT) is a rare cause of gynecological acute abdomen, is easily misdiagnosed and often has a delay in diagnosis. IFTT with paraovarian cysts is most frequently reported in studies. Here, we reported a patient diagnosed with IFTT associated with a paraovarian cyst, and we conducted a literature review for IFTT, aiming to identify valuable information that will be helpful for diagnosis and treatment for fallopian tube torsions. CASE PRESENTATION: A 13-year-old girl presented with a 10-day history of right lower abdominal pain that worsened 2 days before presentation. On presentation, ultrasound showed a 5.8 * 5.5 cm hypoechoic cyst adjacent to the right ovary, and between the cyst and ovary, a tortuous thickened tube was visualized. Laparoscopy revealed a triple torsion of the right fallopian tube with a 6-cm paraovarian cyst, and tubal conservation surgery was performed. The postoperative course was uneventful. Histopathological diagnosis revealed serous papillary cystadenoma. CONCLUSION: Paraovarian cystic dilatation often occurs in adolescence and can induce fallopian torsion when the size of the cyst reaches 5-cm. In our review, the median age of patients diagnosed with IFTT with paraovarian cysts was 15 years old, and the main clinical manifestation was emergency abdominal pain. The associated symptoms were variable, and vomiting was the most commonly associated symptom. Salpingectomy was the most common procedure performed; however, timely surgical intervention can effectively avoid salpingectomy.

A Study of hTERT Promoter Methylation in Circulating Tumour DNAs of Patients with Ovarian Magnificent Tumour.

OBJECTIVE: Human telomerase reverse transcriptase (hTERT), a crucial enzyme for telomere maintenance, has been associated with the development of ovarian cancer (OC). The purpose of this study was to investigate the difference of methylation rates of hTERT promoter in tumour tissues and plasma samples of patients with ovarian magnificent tumour and those with ovarian benign tumour, as well as in plasma samples of healthy women. This study further aimed to establish a possible association between increased methylation rate of hTERT promoter and circulating tumour DNAs (ctDNA) amongst patients with ovarian magnificent tumour. METHODS: Tumour tissue samples and plasma samples were separately obtained from 17 patients with ovarian magnificent tumour (experiment group, group A) and from 15 patients with ovarian benign tumour (control group, group B). Another 15 plasma samples were acquired from healthy women (control group, group C). Promoter methylation was assessed by methylation-specific PCR (MSP). Statistical analysis was conducted using SPSS 22.0. RESULTS: Methylation of hTERT was observed in 76.5% of tumour tissue samples and in 70.6% of plasma samples from patients with ovarian magnificent tumour. It was also observed in 26.7% of tumour tissue samples and 20% of plasma samples from patients with ovarian benign tumour, and in 13.3% of plasma samples from healthy women. Comparing between plasmas and tissues, the respective rates of consistency, sensitivity and specificity were 70.59%, 76.9% and 50% in group A, and 80%, 50% and 90.9% in group B. Hence, the associations of hTERT methylation with ctDNAs (p=0.001) and tumour tissue samples (p=0.012) amongst patients with ovarian magnificent tumour were established. CONCLUSION: An increased methylation of hTERT promoter is related to ctDNAs and tumour tissues of patients with ovarian magnificent tumour.

Breviscapine Alleviates Cognitive Impairments Induced by Transient Cerebral Ischemia/Reperfusion through Its Anti-Inflammatory and Anti-Oxidant Properties in a Rat Model.

Cerebral ischemia/reperfusion (I/R)-induced injury is a common phenomenon of stroke, and the effective treatment for I/R-induced brain tissue damage is limited. Breviscapine has been widely used in China as herbal medicine to treat cardiovascular diseases for hundreds of years and has been demonstrated to possess potent cardiovascular pharmacological effects. This study aims to investigate the neuroprotective effect of breviscapine on cerebral I/R-induced injury. The rat model of middle cerebral artery occlusion (MCAO) was applied in our study. The cerebral I/R rats received multiple injections of breviscapine. All rats were subject to neurological behavior tests by open field test and Morris water maze test. The pro-inflammatory cytokines and oxidative stress marker levels were determined by ELISA and colorimetric analysis, respectively. We demonstrated that administration of breviscapine dose-dependently ameliorated cerebral I/R-induced injury and improved the neurological performance of cerebral I/R rats. Further studies illustrated that breviscapine treatment effectively attenuated inflammatory cytokine expression, reduced oxidative stress, and pro-apoptosis protein expression and inhibited the activation of NF-κB signaling and microglia in the I/R injury tissues. Breviscapine may serve as a single drug or a promising adjuvant that can be used in conjunction with other medicine for the treatment of cerebral I/R-induced injury.

Myomectomy scar pregnancy: a case report and review of the literature.

Myomectomy scar pregnancy (MSP) is a rare disease, which is defined as a gestational sac located within a previous myomectomy scar. MSP is an uncommon late complication of uterine fibroids after myomectomy. We report a case where the implantation site matched the site of the previous myomectomy, and review the existing literature. A 28-year-old pregnant woman presented with vaginal bleeding. She was diagnosed with MSP by ultrasound and magnetic resonance imaging, and then underwent laparotomic enucleation. The patient's postoperative course was uneventful. Taking into account the findings in our case and the seven other reported cases of MSP, we propose that MSP can be divided into three types and that surgical enucleation of the pregnancy mass is an effective treatment.

Discovery of Pimprinine Alkaloids as Novel Agents against a Plant Virus.

Plant viral diseases cause tremendous decreases in crop yield and quality. Natural products have always been a valuable source for lead discovery in medicinal and agricultural chemistry. A series of pimprinine alkaloids and their derivatives were prepared and identified by nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectrometry (HR-MS). The antiviral activities of these alkaloids against tobacco mosaic virus (TMV) were systematically investigated for the first time. Most of the compounds exhibited higher antiviral activities than ribavirin. Compounds 5l, 9h, and 10h, which had similar or higher antiviral activities than ningnanmycin (perhaps the most widely used antiviral agent at present), emerged as new antiviral pilot compounds. This systematic structure-activity-relationship research lays the foundation for simplifying the structure of these alkaloids. The ring-open products, acylhydrazones 9a-9u, were also found to possess good antiviral activities. Moreover, all the synthesized compounds displayed broad-spectrum fungicidal activities. This study provides important information for the research and development of pimprinine alkaloids as novel antiviral agents.

Knockdown of Rap2B, a Ras Superfamily Protein, Inhibits Proliferation, Migration, and Invasion in Cervical Cancer Cells via Regulating the ERK1/2 Signaling Pathway.

Rap2B, belonging to the Ras superfamily, has been implicated in cancer development and functions as a tumor promoter. However, the role of Rap2B in cervical cancer is unknown. In this study, we investigated the expression pattern and biological functions of Rap2B in cervical cancer. The results showed that Rap2B was overexpressed in cervical cancer tissues and cell lines. Knockdown of Rap2B inhibited the proliferation, migration, and invasion of cervical cancer cells. In addition, our tumorigenesis assay showed that Rap2B knockdown suppressed cervical cancer cell growth and metastasis in vivo. We also found that the ERK1/2 signaling pathway is involved in the inhibitory effect of Rap2B knockdown on cervical cancer development. In conclusion, we suggest that Rap2B is an oncogene and may be a promising therapeutic target for cervical cancer.

[Development of a three-dimensional precise conformal radiotherapy treatment planning system based on a cobalt-60 teletherapy unit].

In this paper, a three-dimensional precise conformal radiotherapy treatment planning system based on a cobalt-60 teletherapy unit is introduced. With the help of additional precise target localization and conformal field-shaping devices, the TPS can greatly improve the performance of conventional cobalt-60 teletherapy units in precise target localization, radiotherapy planning and dose delivery. The clinical practices show that the TPS has advantages of reliable precision and an affordable price , and it is urgently needed in our country.

[The 3D PACS image system based on pipeline framework].

We put forward an image rendering system based on pipeline framework for processing and displaying medical images. Compared to original computer graphics algorithms divided into volume rendering and surface rendering, this framework can effectively comprehend methods of computer graphics and image processing, import some new concepts such as vertex buffer, pixel buffer and texture buffer. We implement Shaded Surface Display, Maximum Intensity Projection, Digitally Reconstructed Radiography, Multi planar Reformation, Curved Planar Reformation and Interactive Virtual Endoscopy in our new developed PACS image system.