LECT2, a Ligand for Tie1, Plays a Crucial Role in Liver Fibrogenesis.

Liver fibrosis is a very common condition seen in millions of patients with various liver diseases, and yet no effective treatments are available owing to poorly characterized molecular pathogenesis. Here, we show that leukocyte cell-derived chemotaxin 2 (LECT2) is a functional ligand of Tie1, a poorly characterized endothelial cell (EC)-specific orphan receptor. Upon binding to Tie1, LECT2 interrupts Tie1/Tie2 heterodimerization, facilitates Tie2/Tie2 homodimerization, activates PPAR signaling, and inhibits the migration and tube formations of EC. In vivo studies showed that LECT2 overexpression inhibits portal angiogenesis, promotes sinusoid capillarization, and worsens fibrosis, whereas these changes were reversed in Lect2-KO mice. Adeno-associated viral vector serotype 9 (AAV9)-LECT2 small hairpin RNA (shRNA) treatment significantly attenuates fibrosis. Upregulation of LECT2 is associated with advanced human liver fibrosis staging. We concluded that targeting LECT2/Tie1 signaling may represent a potential therapeutic target for liver fibrosis, and serum LECT2 level may be a potential biomarker for the screening and diagnosis of liver fibrosis.

The Role of Inactivated NF-κB in Premature Ovarian Failure.

Premature ovarian failure (POF) is defined as deployment of amenorrhea due to the cessation of ovarian function in a woman younger than 40 years old. The pathologic mechanism of POF is not yet well understood, although genetic aberrations, autoimmune damage, and environmental factors have been identified. The current study demonstrated that NF-κB inactivation is closely associated with the development of POF based on the data from literature and cyclophosphamide (Cytoxan)-induced POF mouse model. In the successfully established NF-κB-inactivated mouse model, the results showed the reduced expression of nuclear p65 and the increased expression of IκBα in ovarian granulosa cells; the reduced numbers of antral follicles; the reduction of Ki-67/proliferating cell nuclear antigen-labeled cell proliferation and enhanced Fas/FasL-dependent apoptosis in granulosa cells; the reduced level of E2 and anti-Müllerian hormone; the decreased expression of follicle-stimulating hormone receptor and cytochrome P450 family 19 subfamily A member 1 (CYP19A1) in granulosa cells, which was reversed in the context of blocking NF-κB signaling with BAY 11-7082; and the decreased expressions of glucose-regulated protein 78 (GRP78), activating transcription factor 6, protein kinase R-like endoplasmic reticulum kinase, and inositol-requiring enzyme 1 in granulosa cells. Dual-luciferase reporter assay demonstrated that p50 stimulated the transcription of GRP78, and NF-κB affected the expression of follicle-stimulating hormone receptor and promoted granulosa cell proliferation through GRP78-mediated endoplasmic reticulum stress. Taken together, these data indicate, for the first time, that the inactivation of NF-κB signaling plays an important role in POF.

Switchable Regioselective 7-endo or 6-exo Iodocyclization of O-Homoallyl Benzimidates.

We present a facile switchable regioselective 7-endo or 6-exo iodocyclization of O-homoallyl benzimidates here, which affords various iodo-substituted 1,3-oxazines and tetrahydro-1,3-oxazepines in a controllable manner. The products can further undergo substitution reactions to afford a series of rich functionalized target heterocyclic molecules. The developed protocol has the advantages of mild conditions, simple operation, and excellent functional group compatibility.

NIS-Promoted Selective Amino-Diazidation and Amino-Iodoazidation of O-Homoallyl Benzimidates: Synthesis of Vicinal Diazido 1,3-Oxazines and Vicinal Iodoazido 1,3-Oxazines.

Amines, especially those with multi-nitrogen moieties, are widespread in natural products and biologically active compounds. Thus, the development of direct and efficient methods to introduce multiple nitrogen-containing fragments into compounds in one step is highly desirable yet challenging. Herein, we report an NIS-promoted selective amino-diazidation and amino-iodoazidation of O-homoallyl benzimidates with NaN3. By using this protocol, a variety of vicinal diazido-substituted 1,3-oxazines and vicinal iodoazido-substituted 1,3-oxazines were directly synthesized in a controllable manner. Preliminary mechanistic investigations revealed that the reaction operates through a NIS-promoted four-step cascade process. The developed method has the merits of metal-free, excellent functional group compatibility, simple operation, and mild conditions.

A meta-analysis result: Uneven influences of season, geo-spatial scale and latitude on relationship between meteorological factors and the COVID-19 transmission.

Meteorological factors have been confirmed to affect the COVID-19 transmission, but current studied conclusions varied greatly. The underlying causes of the variance remain unclear. Here, we proposed two scientific questions: (1) whether meteorological factors have a consistent influence on virus transmission after combining all the data from the studies; (2) whether the impact of meteorological factors on the COVID-19 transmission can be influenced by season, geospatial scale and latitude. We employed a meta-analysis to address these two questions using results from 2813 published articles. Our results showed that, the influence of meteorological factors on the newly-confirmed COVID-19 cases varied greatly among existing studies, and no consistent conclusion can be drawn. After grouping outbreak time into cold and warm seasons, we found daily maximum and daily minimum temperatures have significant positive influences on the newly-confirmed COVID-19 cases in cold season, while significant negative influences in warm season. After dividing the scope of the outbreak into national and urban scales, relative humidity significantly inhibited the COVID-19 transmission at the national scale, but no effect on the urban scale. The negative impact of relative humidity, and the positive impacts of maximum temperatures and wind speed on the newly-confirmed COVID-19 cases increased with latitude. The relationship of maximum and minimum temperatures with the newly-confirmed COVID-19 cases were more susceptible to season, while relative humidity's relationship was more affected by latitude and geospatial scale. Our results suggested that relationship between meteorological factors and the COVID-19 transmission can be affected by season, geospatial scale and latitude. A rise in temperature would promote virus transmission in cold seasons. We suggested that the formulation and implementation of epidemic prevention and control should mainly refer to studies at the urban scale. The control measures should be developed according to local meteorological properties for individual city.

Giant broad ligament leiomyoma with postoperative infection diagnosed with contrast-enhanced ultrasound: Case report and literature review.

A 33-year-old woman of giant broad ligament leiomyoma with myxoid degeneration was misdiagnosed as ovarian tumor. The patient underwent a transabdominal myomectomy and developed a pelvic infection after operation diagnosed with contrast-enhanced ultrasound. She was cured and ultimately discharged after symptomatic treatment. Only 21 cases of giant broad ligament leiomyomas with a diameter larger than 12 cm were included. The present systematic review aimed to increase awareness of the clinical characteristics and treatment methods of giant broad ligament leiomyoma, and reduce the rates of misdiagnosis and postoperative complications.

AI detection of mild COVID-19 pneumonia from chest CT scans.

OBJECTIVES: An artificial intelligence model was adopted to identify mild COVID-19 pneumonia from computed tomography (CT) volumes, and its diagnostic performance was then evaluated. METHODS: In this retrospective multicenter study, an atrous convolution-based deep learning model was established for the computer-assisted diagnosis of mild COVID-19 pneumonia. The dataset included 2087 chest CT exams collected from four hospitals between 1 January 2019 and 31 May 2020. The true positive rate, true negative rate, receiver operating characteristic curve, area under the curve (AUC) and convolutional feature map were used to evaluate the model. RESULTS: The proposed deep learning model was trained on 1538 patients and tested on an independent testing cohort of 549 patients. The overall sensitivity was 91.5% (195/213; p < 0.001, 95% CI: 89.2-93.9%), the overall specificity was 90.5% (304/336; p < 0.001, 95% CI: 88.0-92.9%) and the general AUC value was 0.955 (p < 0.001). CONCLUSIONS: A deep learning model can accurately detect COVID-19 and serve as an important supplement to the COVID-19 reverse transcription-polymerase chain reaction (RT-PCR) test. KEY POINTS: • The implementation of a deep learning model to identify mild COVID-19 pneumonia was confirmed to be effective and feasible. • The strategy of using a binary code instead of the region of interest label to identify mild COVID-19 pneumonia was verified. • This AI model can assist in the early screening of COVID-19 without interfering with normal clinical examinations.

[Remitting Seronegative Symmetrical Synovitis with Pitting Edema associated with Lung Malignancy:Case Report and Literature Review].

Remitting seronegative symmetrical synovitis with pitting edema(RS3PE),the inflammatory arthritis attacking mainly elderly males,is characterized by symmetrical synovitis with pitting edema of the dorsum of hands and feet and the absence of rheumatoid factor.RS3PE commonly accompanies malignant tumor,infections and other diseases.Here we report a case of RS3PE associated with lung malignancy and review other six cases to summarize the clinical features,treatment and prognosis.

Copper/DTBP-Promoted Oxyselenation of Propargylic Amines with Diselenides and CO2: Synthesis of Selenyl 2-Oxazolidinones.

A highly efficient electrophilic oxyselenation of propargylic amines with diselenides and CO2 under atmospheric pressure promoted by copper/DTBP is reported. Various biologically important selenyl 2-oxazolidinones were produced in moderate to excellent yields. The developed method features a broad substrate scope, easy scalability, and mild reaction conditions.

Role of nuclear factor-κB pathway in the transition of mouse secondary follicles to antral follicles.

Nuclear factor-κB (NF-κB) signaling is involved in regulating a great number of normal and abnormal cellular events. However, little is known about its role in ovarian follicular development. In this study, we found NF-κB signaling is activated during the transition from secondary to antral follicles. We generated active NF-κB mice and found that antral follicular numbers were higher than wild-type ovaries. Activation of NF-κB signaling could enhance granulosa cell proliferation and regress granulosa cell apoptosis of mouse ovarian follicles. Higher follicle-stimulating hormone receptor (FSHR) and luteinizing hormone/choriogonadotropin receptor expressions were observed in active NF-κB ovaries compared to wild type. Furthermore, we confirmed that NF-κB signaling was indeed involved in the granulosa cell viability and proliferation through FSHR using COV434 cell line. This is the first experimental evidence that NF-κB signaling is implicated in the control of follicular development through FSHR and its corresponding target molecules, which might be achieved by targeting proliferation and apoptosis in follicular granulosa cells.

Synthesis of Sulfonylated Lactams by Copper-Mediated Aminosulfonylation of 2-Vinylbenzamides with Sodium Sulfinates.

Treatment of 2-vinylbenzamide derivatives with sulfinate sodium in the presence of Cu(NO3)2·3H2O led to an intra/intermolecular aminosulfonylation reaction to produce sulfonylated lactams in moderate to good yields. The developed method features the easily available and stable sulfone reagents, ease of operation, and a broad functional group tolerance.

Evaluation of D2-plus radical resection for gastric cancer with pyloric invasion.

BACKGROUND: The optimal lymphadenectomy for gastric cancer (GC) with pyloric invasion is controversial because the pattern of lymph node metastasis is different from that of distal GC. The rate of lymph node metastasis into the posterior area of the pancreatic head and hepatoduodenal ligament is high. This study evaluated the estimated benefit of radical gastrectomy with D2-plus lymphadenectomy in patients with pyloric invasion. METHODS: All patients with GC invading the pylorus who underwent curative surgical resection with D2-plus lymphadenectomy between February 2013 and September 2015 were enrolled in the study. The index of estimated benefit from lymph node dissection (IEBLD) was calculated by multiplying the incidence of metastasis to each lymph node station by the 3-year overall survival (OS) rate of patients with metastasis to that station. RESULTS: In total, 128 patients were eligible. The rate of lymph node metastasis and the 3-year OS rate (and IEBLD) of the patients with metastasis to lymph nodes were 14.3 and 44.4% (5.56) for No. 8p, 10.9 and 35.7% (3.89) for No. 12b, 9.5 and 33.3% (3.13) for No. 12p, 18.8 and 54.2% (10.19) for No. 13, and 21.8 and 53.6% (11.68) for No. 14v, respectively. CONCLUSIONS: In radical gastrectomy for GC with pyloric invasion, some survival benefit was observed with dissection of the No. 13 and No. 14 lymph nodes, but there was no survival benefit with dissection of the No. 8p lymph nodes. The No. 12b and No. 12p lymph nodes may be better to dissect in cT3 GC patients with pyloric invasion. TRIAL REGISTRATION: http://ClinicalTrials.gov Identifier: NCT01836991. Date of registration: April 17, 2013.

Synthesis of acyloxyl pyrazolines by copper-mediated aminoacyloxylation of unsaturated ketohydrazones.

An efficient and step-economical copper-mediated intra-/intermolecular aminoacyloxylation of ß,γ-unsaturated hydrazones has been developed. Copper carboxylates serve as both reaction promoters and carboxylate sources in these easily conducted reactions. This method provides straightforward access to diversely useful acyloxyl pyrazolines, which are hard to access traditionally, in good to excellent yields.

Structure-Property Relationship Study of Donor and Acceptor 2,6-Disubstituted BODIPY Derivatives for High Performance Dye-Sensitized Solar Cells.

Seven donor and acceptor 2,6-disubstituted 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) dyes have been synthesized and characterized. Including MPBTCA, which is a known compound, the seven BODIPY dyes have been characterized by varied physical methods, such as UV/Visible absorption spectroscopy, low energy photo-electron spectroscopy (AC-2), and HOMO-LUMO DFT/TDDFT calculation. All seven BODIPY dyes have absorption λmax around 535-545 nm, which is significantly longer than 499 nm of 4,4-difluoro-1,3,5,7,8-pentamethyl-4-bora-3a,4a-diaza-s-indacene (PM 546). Having structural variation on donor group, acceptor group, donor π-spacer, acceptor π-spacer, and the substituent on boron, some BODIPY dyes exhibit small extinction coefficients or spectral integrals in solution (MPCtBTCA, MPBT-pyO, MPBTT-pyO, MTBTCA), broadening absorption spectral profile (MTBTCA), weak intramolecular charge transfer characteristics (MPBT-pyO, MPBTT-pyO, MTBTCA), too low LUMO energy level (PPBTCA), or insufficient dye-uptake by TiO2 FTO (MPBT-pyO, MPBTT-pyO, MTBTCA). Two of the seven BODIPY dyes, MPBTCA and MPBTTCA, do not show the adverse properties like other BODIPY dyes. With our improved TiO2 FTO (fluorine doped tin oxide) dyeing method, namely a solution dropping method, high performance dye-sensitized solar cells (DSCs) have been realized by MPBTCA and MPBTTCA photosensitizers. Power conversion efficiencies of 6.3 and 6.4 % have been achieved by MPBTCA and MPBTTCA DSCs, respectively. To the best of our knowledge, MPBTCA and MPBTTCA are the most efficient dyes for the donor and acceptor 2,6-disubstituted BODIPY DSCs so far.

Palladium-Catalyzed Construction of Tetracyclic Scaffolds via the 1,7-Enyne Carbocyclization/Iodophenol Dearomatization Cascade.

An efficient palladium-catalyzed dearomatizing [2+2+1] carbocyclization of 1,7-enynes with iodophenols has been developed. A type of tetracyclic scaffold was built in this reaction, exhibiting a broad substrate scope with moderate to excellent yields. More importantly, this method provides a potential strategy for the synthesis of tetracyclic skeleton natural products.

Dimethyl phenyl piperazine iodide (DMPP) induces glioma regression by inhibiting angiogenesis.

1,1-Dimethyl-4-phenyl piperazine iodide (DMPP) is a synthetic nicotinic acetylcholine receptor (nAChR) agonist that could reduce airway inflammation. In this study, we demonstrated that DMPP could dramatically inhibit glioma size maintained on the chick embryonic chorioallantoic membrane (CAM). We first performed MTT and BrdU incorporation experiments on U87 glioma cells in vitro to understand the mechanism involved. We established that DMPP did not significantly affect U87 cell proliferation and survival. We speculated that DMPP directly caused the tumor to regress by affecting the vasculature in and around the implanted tumor on our chick CAM model. Hence, we conducted detailed analysis of DMPP's inhibitory effects on angiogenesis. Three vasculogenesis and angiogenesis in vivo models were used in the study which included (1) early chick blood islands formation, (2) chick yolk-sac membrane (YSW) and (3) CAM models. The results revealed that DMPP directly suppressed all developmental stages involved in vasculogenesis and angiogenesis - possibly by acting through Ang-1 and HIF-2α signaling. In sum, our results show that DMPP could induce glioma regression grown on CAM by inhibiting vasculogenesis and angiogenesis.

[A Hyperspectral Imagery Anomaly Detection Algorithm Based on Gauss-Markov Model].

With the development of spectral imaging technology, hyperspectral anomaly detection is getting more and more widely used in remote sensing imagery processing. The traditional RX anomaly detection algorithm neglects spatial correlation of images. Besides, it does not validly reduce the data dimension, which costs too much processing time and shows low validity on hyperspectral data. The hyperspectral images follow Gauss-Markov Random Field (GMRF) in space and spectral dimensions. The inverse matrix of covariance matrix is able to be directly calculated by building the Gauss-Markov parameters, which avoids the huge calculation of hyperspectral data. This paper proposes an improved RX anomaly detection algorithm based on three-dimensional GMRF. The hyperspectral imagery data is simulated with GMRF model, and the GMRF parameters are estimated with the Approximated Maximum Likelihood method. The detection operator is constructed with GMRF estimation parameters. The detecting pixel is considered as the centre in a local optimization window, which calls GMRF detecting window. The abnormal degree is calculated with mean vector and covariance inverse matrix, and the mean vector and covariance inverse matrix are calculated within the window. The image is detected pixel by pixel with the moving of GMRF window. The traditional RX detection algorithm, the regional hypothesis detection algorithm based on GMRF and the algorithm proposed in this paper are simulated with AVIRIS hyperspectral data. Simulation results show that the proposed anomaly detection method is able to improve the detection efficiency and reduce false alarm rate. We get the operation time statistics of the three algorithms in the same computer environment. The results show that the proposed algorithm improves the operation time by 45.2%, which shows good computing efficiency.

Gold-catalyzed tandem [3,3]-propargyl ester rearrangement leading to (E)-1H-inden-1-ones.

An efficient method for the synthesis of (E)-1H-inden-1-ones using gold-catalyzed tandem [3,3]-propargyl ester rearrangement followed by Michael addition under mild reaction conditions has been developed. The resulting products are important frameworks found in numerous natural products and pharmaceutically active compounds, as well as being valuable intermediates in organic synthesis.

Electrophilic ipso-iodocyclization of N-benzyl-N-(1-naphthyl)propiolamides: synthesis of complex polycyclic lactams.

An intramolecular electrophilic ipso-iodocyclization of N-benzyl-N-(1-naphthyl)propiolamides combined with the Friedel-Crafts-type reaction for the synthesis of complex polycyclic lactams is reported. The resulting iodinated cyclization product can provide a very useful handle for further structural manipulation.

Slit/Robo1 signaling regulates neural tube development by balancing neuroepithelial cell proliferation and differentiation.

Formation of the neural tube is the morphological hallmark for development of the embryonic central nervous system (CNS). Therefore, neural tube development is a crucial step in the neurulation process. Slit/Robo signaling was initially identified as a chemo-repellent that regulated axon growth cone elongation, but its role in controlling neural tube development is currently unknown. To address this issue, we investigated Slit/Robo1 signaling in the development of chick neCollege of Life Sciences Biocentre, University of Dundee, Dundee DD1 5EH, UKural tube and transgenic mice over-expressing Slit2. We disrupted Slit/Robo1 signaling by injecting R5 monoclonal antibodies into HH10 neural tubes to block the Robo1 receptor. This inhibited the normal development of the ventral body curvature and caused the spinal cord to curl up into a S-shape. Next, Slit/Robo1 signaling on one half-side of the chick embryo neural tube was disturbed by electroporation in ovo. We found that the morphology of the neural tube was dramatically abnormal after we interfered with Slit/Robo1 signaling. Furthermore, we established that silencing Robo1 inhibited cell proliferation while over-expressing Robo1 enhanced cell proliferation. We also investigated the effects of altering Slit/Robo1 expression on Sonic Hedgehog (Shh) and Pax7 expression in the developing neural tube. We demonstrated that over-expressing Robo1 down-regulated Shh expression in the ventral neural tube and resulted in the production of fewer HNK-1(+) migrating neural crest cells (NCCs). In addition, Robo1 over-expression enhanced Pax7 expression in the dorsal neural tube and increased the number of Slug(+) pre-migratory NCCs. Conversely, silencing Robo1 expression resulted in an enhanced Shh expression and more HNK-1(+) migrating NCCs but reduced Pax7 expression and fewer Slug(+) pre-migratory NCCs were observed. In conclusion, we propose that Slit/Robo1 signaling is involved in regulating neural tube development by tightly coordinating cell proliferation and differentiation during neurulation.