Constructing artificial gap junctions to mediate intercellular signal and mass transport.

Natural gap junctions are a type of channel protein responsible for intercellular signalling and mass communication. However, the scope of applications for these proteins is limited as they cannot be prepared at a large scale and are unable to spontaneously insert into cell membranes in vitro. The construction of artificial gap junctions may provide an alternative strategy for preparing analogues of the natural proteins and bottom-up building blocks necessary for the synthesis of artificial cells.

Forrestiacids E-K: Further [4 + 2]-Type Triterpene-Diterpene Hybrids as Potential ACL Inhibitors from the Vulnerable Conifer .

Seven [4 + 2]-type triterpene-diterpene hybrids derived from a rearranged or a normal lanostane unit (dienophile) and an abietane moiety (diene), forrestiacids E-K (-, respectively), were further isolated and characterized from (a vulnerable conifer endemic to China). The intriguing molecules were revealed with the guidance of an LC-MS/MS-based molecular ion networking strategy combined with conventional phytochemical procedures. Their chemical structures with absolute configurations were established by spectroscopic data, chemical transformation, electronic circular dichroism calculations, and single-crystal X-ray diffraction analysis.

Clinical Implications of Necroptosis Genes Expression for Cancer Immunity and Prognosis: A Pan-Cancer Analysis.

Background: Necroptosis, a form of programmed cell death, is increasingly being investigated for its controversial role in tumorigenesis and progression. Necroptosis suppresses tumor formation and tumor development by killing tumor cells; however, the necrotic cells also promote tumor formation and tumor development the immunosuppressive effect of necroptosis and inflammatory response caused by cytokine release. Thus, the exact mechanism of necroptosis in pan-cancer remains unknown.

Liriogerphines A-D, a Class of Sesquiterpene-Alkaloid Hybrids from the Rare Chinese Tulip Tree Plant.

Liriogerphines A-D (, respectively), an unprecedented class of hybrids of germacranolide-type sesquiterpenoids and aporphine-type alkaloids, were isolated from the rare medicinal plant . Their structures were elucidated by comprehensive spectroscopic analyses combined with electronic circular dichroism calculations and X-ray crystallographic data. Biosynthetically, an aza-Michael addition reaction is proposed to be involved in the assemblies of this class of hybrids.

Beshanzoides A-D, unprecedented cycloheptanone-containing polyketides from P-4-1, an endophytic fungus of the endangered conifer .

A number of previously undescribed (1-7) and structurally related known (8-17) isobenzofuran-type polyketides were obtained from the fermentation of P-4-1, an endophytic fungus isolated from the fresh trunk bark of the critically endangered conifer . Beshanzoides A-D (1-4, resp.) feature a cycloheptanone-containing isobenzofuran ring system hitherto unknown, which might be biosynthesized two steps of aldol reactions starting from a common co-occurring isobenzofuran-type polyketide as the precursor.

Design of a microfluidic chip consisting of micropillars and its use for the enrichment of nasopharyngeal cancer cells.

The aim of the present study was to discuss the design of a microfluidic chip consisting of columns, and its use for the enrichment of nasopharyngeal cancer (NPC) cells. A microfluidic chip experiment was simulated using FLUENT software. Within the microfluidic chip, aptamers were bound to the reaction chamber (consisting of columns) using a biotin-avidin system.

Structural Modifications of Diarylpyrimidine-quinolone Hybrids as Potent HIV-1 NNRTIs with an Improved Drug Resistance Profile.

Earlier we reported the identification of diarylpyrimidine-quinolone hybrids as a new class of HIV-1 NNRTIs. A few of these hybrids displayed moderate inhibitory activity against wt HIV-1 replication at submicromolar level, however, all of them lacked inhibitory activity against the double mutant virus (K103N/Y181C), which is the most prevalent NNRTI resistant-associated double mutant observed in the clinic. In the present study, we designed and synthesized a new series of diarylpyrimidine-quinolone hybrids featuring a halogen group at C-6' position of quinolone ring.

Antibacterial mechanism and activities of black pepper chloroform extract.

Black pepper extracts reportedly inhibit food spoilage and food pathogenic bacteria. This study explored the antimicrobial activity of black pepper chloroform extract (BPCE) against Escherichia coli and Staphylococcus aureus. The antibacterial mechanism of BPCE was elucidated by analyzing the cell morphology, respiratory metabolism, pyruvic acid content, and ATP levels of the target bacteria.

Pyrimidine sulfonylacetanilides with improved potency against key mutant viruses of HIV-1 by specific targeting of a highly conserved residue.

Based on molecular simulation, the etravirine-VRX-480773 hybrids previously disclosed by our group were optimized to yield novel pyrimidine sulfonylacetanilides 8 with improved activity against a panel of seven clinically relevant single and double mutant strains of HIV-1. The improvement in potency in this in vitro model of HIV RNA replication partly validates the mechanism by which this class of allosteric pyrimidine derivatives inhibits the reverse transcriptase (RT), and represents a remarkable step forward in the development of anti-HIV drugs.

Anti-HIV diarylpyrimidine-quinolone hybrids and their mode of action.

A molecular hybridization approach is a powerful tool in the design of new molecules with improved affinity and efficacy. In this context, a series of diarylpyrimidine-quinolone hybrids were synthesized and evaluated against both wt HIV-1 and mutant viral strains. The most active hybrid 5a displayed an EC50 value of 0.

[Study on hypoglycemic effect and mechanism of total flavonoids of Propolis in STZ diabetic rats].

Objective: To study hypoglycemic effect and mechanism of the total flavonoids of Propolis (TFP) in the STZ diabetic rats.

Methods: The model of type 2 diabetic rats was induced by high-fat diet feeding for 4 weeks combined with intraperitoneal injection of streptozotocin (STZ). Then the rats without above-mentioned treatment were selected as the normal control group,the diabetic rats were randomly divided into four groups by blood glucose, the model control group, high doses (240 mg/kg), medium doses (120 mg/kg) and low doses (60 mg/kg) TFP groups.

Synthesis and biological evaluation of DAPY-DPEs hybrids as non-nucleoside inhibitors of HIV-1 reverse transcriptase.

A series of new DAPY-DPEs hybrids, combined the important pharmacophores of DAPYs and DPEs, has been synthesized and biologically evaluated for their anti-HIV activities against wild-type HIV-1 strain IIIB, double RT mutant (K103N+Y181C) strain RES056 and HIV-2 strain ROD in MT-4 cell cultures. Many promising candidates with potent inhibitory activity (wild-type) within the EC50 range from 0.16 to 0.

Optimization of extraction conditions of areca seed polyphenols and evaluation of their antioxidant activities.

Polyphenols are functional compounds in plants, which possess many bioactivities beneficial for humans. The aim of this study was to establish a highly efficient method for extracting polyphenol compounds from areca seeds and further to identify polyphenols and antioxidant properties of the seeds. A quadratic general rotary unitized design was used to determine the optimal extraction process.

Synthesis and biological evaluation of CHX-DAPYs as HIV-1 non-nucleoside reverse transcriptase inhibitors.

A series of new diarylpyrimidines (DAPYs) characterized by a halogen atom on the methylene linker between wing I and the central pyrimidine ring was synthesized and evaluated for their anti-HIV activity in MT-4 cell cultures. The two most promising compounds 7f and 7g showed excellent activity against wild-type HIV-1 with low nanomolar EC50 values of 0.005 and 0.

Structural modifications of CH(OH)-DAPYs as new HIV-1 non-nucleoside reverse transcriptase inhibitors.

A series of CR2(OH)-diarylpyrimidine derivatives (CR2(OH)-DAPYs) featuring a hydrophobic group at CH(OH) linker between wing I and the central pyrimidine were synthesized and evaluated for their anti-HIV activity in MT-4 cell cultures. All the target compounds except for compound 3k displayed inhibitory activity against HIV-1 wild-type with EC50 values ranging from 7.21±1.

Towards new C6-rigid S-DABO HIV-1 reverse transcriptase inhibitors: synthesis, biological investigation and molecular modeling studies.

A series of C6-rigid S-DABO analogs characterized by a substituted benzoyl group at C6 position of the pyrimidine ring has been synthesized and biological evaluation as NNRTIs against wild-type HIV-1 strain IIIB, double RT mutant (K103N+Y181C) strain RES056 as well as HIV-2 strain ROD in MT-4 cell cultures. Most of the compounds exhibited moderate antiviral activities. Among them, compound 7q displayed the highest anti-HIV-1 activity with an EC50 value of 0.

[Comparative study on effect and safty of treating on calcaneus fractures with manipulative reduction with percutaneous K-wire fixation].

Objective: To explore the clinical effects and safty of manipulative reduction with percutaneous poking K-wire fixation for the treatment of the calcaneus fractures and analyze the indication of the minimal invasion.

Methods: From December 2008 to December 2011,135 closed calcaneal fractures cases were divided randomly into poking group and plate group, treated respectively by percutaneous poking reduction and operative reduction. In poking group, there were 69 cases (82 feet) including 60 males and 9 females, with an average age of (43.

[Case-control study on bone setting manipulation for the treatment of over degree II supination-eversion fractures of ankle joint].

Objective: To explore therapeutic effects of bone setting manipulation for the treatment of over degree II supination-eversion fractures of ankle,and analyze manipulative reduction mechanism.

Methods: From 2005 to 2008, 95 patients with over degree II supination-eversion fractures of ankle were treated respectively by manipulation and operation. There were 43 cases [11 males and 32 females with an average age of (44.

Grade classification of neuroepithelial tumors using high-resolution magic-angle spinning proton nuclear magnetic resonance spectroscopy and pattern recognition.

Clinical data have shown that survival rates vary considerably among brain tumor patients, according to the type and grade of the tumor. Metabolite profiles of intact tumor tissues measured with high-resolution magic-angle spinning proton nuclear magnetic resonance spectroscopy (HRMAS (1)H NMRS) can provide important information on tumor biology and metabolism. These metabolic fingerprints can then be used for tumor classification and grading, with great potential value for tumor diagnosis.

NMR studies on chiral intermediates in the total synthesis of (+)-biotin from D-mannose.

The chemical structure and stereochemistry of 12 intermediates in the total synthesis of (+)-biotin starting from D-mannose as chiral pool were completely assigned using one- and two-dimensional NMR experiments, including 1D selective NOE, DEPT, COSY, HSQC and HMBC.

[Relationship between the expression of P-glycoprotein, glutathione S-transferase-pi and thymidylate synthase proteins and adenosine triphosphate tumor chemosensitivity assay in cervical cancer].

Objective: To explore the feasibility of the adenosine triphosphate-tumor chemosensitivity assay (ATP-TCA) in human cervical cancer chemosensitivity testing and to analyze the relationship between the three drug resistance-associated proteins: P-glycoprotein (P-gp); glutathione S-transferase-pi (GST-pi); thymidylate synthase (TS) and ATP-TCA.

Methods: ATP-TCA was used to detect the sensitivity of 35 specimens of fresh cervical cancer to six cytotoxic drugs as follows: paclitaxel (TAX), cisplatin (DDP), bleomycin (BLM), gemcitabine (GEM), 5-fluorouracil (5-FU), irinotecan (CPT-11). Consecutive sections from 35 cases of cervical cancer were assessed immunohistochemically for expression of P-gp, GST-pi and TS proteins.

[Expression of KiSS-1, matrix metalloproteinase-9, nuclear factor-kappaBp65 in ovarian tumour].

Objective: To investigate the expression and correlation of KiSS-1, matrix metalloproteinase-9 (MMP-9) and nuclear factor (NF)-kappaBp65 proteins in primary epithelial ovarian tumors.

Methods: Expression of KiSS-1, MMP-9, NF-kappaBp65 proteins in primary ovarian epithelial tumors (malignant n = 50, borderline tumor n = 20, benign adenoma n = 20, normal tissue n = 10) was evaluated by immunohistochemical staining.

Results: Expression of metastin protein in primary epithelial ovarian cancers was significantly higher than that in ovarian benign adenoma (P < 0.

[Expression of lysophosphatidic acid receptor in human ovarian cancer cell lines 3AO, SKOV3, OVCAR3 and its significance].

Objective: To investigate the expressions of lysophosphatidic acid (LPA) receptors at both mRNA and protein levels and their biological significance in different human ovarian cancer cell lines.

Methods: Reverse transcription-polymerase chain reaction (RT-PCR), streptovidin peroxidase-conjugated (SP) immunohistochemical assay and Western blotting were employed to measure the expression levels of LPA(1), LPA(2) and LPA(3) mRNA and LPA(2) and LPA(3) protein in cultured human ovarian cancer cell lines 3AO.SKOV3, and OVCAR3.