Comparative analysis of transvaginal natural orifice transluminal endoscopic surgery versus laparoendoscopic single-site sacrocolpopexy for pelvic organ prolapse: A propensity score matching study.

Purpose: To compare the safety, feasibility, and effectiveness of transvaginal natural orifice transluminal endoscopic sacrocolpopexy (vNOTES-SC) and laparoendoscopic single-site sacrocolpopexy (LESS-SC) for pelvic organ prolapse (POP). Method: Ninety-four patients with POP who underwent vNOTES-SC or LESS-SC from October 2016 to November 2018 were included. The propensity score matching method was used for 1:1 matching between the two surgery groups. After matching, the general perioperative indicators, surgical complications, and the subjective and objective therapeutic effects of the two groups 3 years post-surgery were analyzed. Results: After matching, 36 patients in each group were included, exhibiting balanced and comparable baseline data and an average follow-up of 48.6 ± 7.44 months. The operation time and postoperative hospitalization days were significantly reduced in the vNOTES-SC group (P < 0.05). However, perioperative complication incidence was not significantly different between the two groups (P > 0.05). Additionally, no significant differences were detected in de novo stress urinary incontinence (16.7% vs. 13.9%), de novo overactive bladder (de novo OAB, 8.3% vs. 0.0%), urination disorder (2.8% vs. 0.0%), defecation disorder (0.0% vs. 2.8%), lumbosacral pain (0.0% vs. 2.8%), or mesh complication (2.8% vs. 5.6%) incidences between the vNOTES-SC and LESS-SC groups (P > 0.05). Prolapse recurrence was not reported in either group. The quantitative description of pelvic organ position (POP-Q), Pelvic Floor Impact Questionnaire-7 (PFIQ-7), and Patient Global Impression of Improvement scale (PGI-I) scores showed improvement after the operation, but no significant differences were observed between the two groups (P > 0.05). Conclusion: The 3-year follow-up revealed that vNOTES-SC and LESS-SC had similar complications and efficacy rates. Compared with LESS-SC, vNOTES-SC resulted in shorter operation time and fewer postoperative hospitalization days (corresponding to the enhanced recovery after surgery [ERAS] concept), along with better cosmetic results without a scar. Therefore, our study findings suggest that clinicians should choose the surgery method based on the specific situation, and we recommend choosing vNOTES-SC when both surgeries are suitable.

Emissive Nanoparticles from Co-assembly of Metallatetragon and Amphiphilic Tetraphenylethylene for Cancer Theranostics.

Platinum(II)-based metallacycles/cages have obtained tremendous attention due to their fascinating topology and wide range of applications, such as fluorescent materials, cell imaging, and tumor treatment. In this work, a metallatetragon (1) was constructed from 4-(4-(1,2,2-triphenylvinyl)phenyl)pyridine (2) and 90° cis-Pt(II) (Pt) in acetone through the strategy called "coordination driven self-assembly". Interestingly, through co-assembly of 1 and poly(ethylene glycol)-modified tetraphenylethylene (TPE-PEG22), fluorescent nanotheranostics, which could generate singlet oxygen (1O2) under the NIR irradiation and release Pt drugs under a low-pH microenvironment, were prepared successfully. The obtained theranostics could realize living cell imaging and synergistic chemo-photodynamic therapy in vitro and in vivo.

Pathogenicity virulence of Beauveria spp. and biosafety of the BbMQ strain on adult ectoparasitic beetles, Dastarcus helophoroides Fairmaire (Coleoptera: Colydiidae).

Introduction: Beauveria spp. and Dastarcus helophoroides Fairmaire adults were simultaneously released to attack elder larvae or pupae of Monochamus alternatus in pine forests in China. However, little is known about the pathogenicity virulence and biosafety of Beauveria spp. on beneficial adults of D. helophoroides, and specific Beauveria bassiana (Bb) strains should be selected for synthetic release together with D. helophoroides. Methods: A total of 17 strains of Beauveria spp. were collected, isolated, and purified, and then their mortality, cadaver rate, LT50, spore production, spore germination rate, and growth rate of D. helophoroide adults were calculated based on 0-20 days data after spore suspension and powder contact. Results and discussion: The lethality rate of BbMQ, BbFD, and BbMH-03 strains to D. helophoroides exceeded 50%, and the cadaver rate reached 70.6%, among which the mortality rate (82.22%), cadaver rate (47.78%), spore production (1.32 × 109 spores/ml), spore germination rate (94.71%), colony dimension (49.15 mm2), and LT50 (10.62 d) of the BbMQ strain were significantly higher than those of other strains (P < 0.01), and the mortality of D. helophoroides adults increased significantly with increased spore suspension concentration, with the highest mortality reaching 92.22%. This strain was identified as Beauveria bassiana by morphological and molecular methods, while the BbWYS strain had a minimum lethality of only 5.56%, which was safer compared to other strains of adult D. helophoroide. Consequently, the biological characteristics and pathogenicity of different Beauveria bassiana strains varied significantly in their effects on D. helophoroide adults, and the safety of different strains should be assessed when they are released or sprayed to control multiple pests in the forest. The BbMQ strain should not be simultaneously sprayed with releasing D. helophoroide adults in the same forest, while the BbWYS strain can be used in concert with D. helophoroide to synergize their effect.

Pillar[5]arene-Derived Terpyridinepalladium(II) Complex: Synthesis, Characterization, and Application in Green Catalysis.

Metal nanoparticle catalysts have attracted great interest because they possess high surface-to-volume ratios and exhibit a very large number of catalytically active sites per unit area. However, high surface-to-volume ratios will induce nanoparticle aggregates during the catalytic reactions, making them lose their catalytic activity. In this work, a monoterpyridine-unit-functionalized pillar[5]arene (TP5) was synthesized successfully, which can be used as anchoring sites for the controllable preparation of well-dispersed palladium nanoparticles [TP5/Pd(0) NPs]. The as-prepared TP5/Pd(0) NPs were fully characterized by X-ray photoelectron spectroscopy, transmission electron microscopy, and powder X-ray diffraction. Importantly, the ultrafine TP5/Pd(0) NPs are found to be excellent and reusable catalysts for the reduction of nitrophenols in aqueous solution.

Nano-Theranostics Constructed from Terpyridine-Modified Pillar [5]arene-Based Supramolecular Amphiphile and Its Application in Both Cell Imaging and Cancer Therapy.

Theranostics play an important role in cancer treatment due to its realized real-time tracking of therapeutic efficacy in situ. In this work, we have designed and synthesized a terpyridine-modified pillar [5]arenes (TP5). By the coordination of terpyridine and Zn2+, the complex TP5/Zn was obtained. Then, supramolecular amphiphile can be constructed by using host-guest complexation between a polyethylene glycol contained guest (PM) and TP5/Zn. Combining the fluorescence properties from the terpyridine group and the amphiphilicity from the system, the obtained TP5/Zn/PM can further be self-assembled into fluorescent particles with diameters of about 150 nm in water. The obtained particles can effectively load anti-cancer drugs and realize living cell imaging and a precise release of the drugs.

Pillar[5]arene-based [1]rotaxanes with salicylaldimine as the stopper: synthesis, characterization and application in the fluorescence turn-on sensing of Zn2+ in water.

Two pillar[5]arene-based [1]rotaxanes with salicylaldimine as the stopper were synthesized and characterized fully, and could be further applied in the fluorescence turn-on sensing of Zn2+ in water.

Upregulation of CENPM facilitates lung adenocarcinoma progression via PI3K/AKT/mTOR signaling pathway.

Centromere protein M (CENPM) is essential for chromosome separation during mitosis. However, its roles in lung adenocarcinoma (LUAD) progression and metastasis remain unknown. In this study, we aimed to explore the effects of CENPM on LUAD progression as well as the underlying mechanisms. We analyzed the expression of CENPM and its correlation with clinicopathological characteristics using GEO LUAD chip datasets and TCGA dataset. We further investigated the impact of CENPM on LUAD and . In silico analysis and qRT-PCR revealed that CENPM is upregulated in LUAD compared with that in normal lung tissues. Via gain/loss-of-function assays, we further found that CENPM promotes the LUAD cell cycle, cell proliferation, migration and invasion, and inhibits cell apoptosis. The study showed that loss of CENPM inhibits the growth of A549 xenografts. Furthermore, we found that CENPM can promote the phosphorylation of mTOR rather than directly affect the mTOR content. Inhibition of mTOR activity abrogates the promoting effects of CENPM on cell cycle progression, cell proliferation, migration and invasion. Taken together, these results show that CENPM plays an important role in the growth and metastasis of LUAD and may be a promising therapeutic target in LUAD.

Development of a human serum albumin structure-based fluorescent probe for bioimaging in living cells.

Forming a stable complex is a prerequisite for intramolecular charge transfer (ICT) probe to recognize proteins. Herein, a human serum albumin (HSA) structure-based fluorescent probe DNPM was fabricated successfully with fully considering its binding to the primary sites in HSA. Molecular simulation was used to assist the probe design. Two ICT ligands DNPM and MPM were initially designed. Both DNPM and MPM had favorable HSA binding abilities, but only DNPM had a satisfactory HSA sensitivity. Electromagnetic coupling played a key role in DNPM fluorescence enhancement. Due to the electromagnetic environment difference in protein structure, DNPM only exhibited strong sensitivity to serum albumins. DNPM could bind to Sudlow site I and site II in HSA but could not be displaced from its binding sites by common site specific drugs (e.g. phenylbutazone and ibuprofen). Besides, DNPM exhibited great potential for illumining serum albumin in living cells. The results provided a beneficial approach for designing and synthesizing high sensitive and selective fluorescent probes for proteins.

A new species of Glyptapanteles Ashmead (Hymenoptera, Braconidae, Microgastrinae) within Macrobrochis gigas (Lepidoptera, Arctiidae, Lithosiidae) in Fujian, China.

The south-east coastal area of Fujian, China, belongs to the Oriental Realm, and is characterized by a high insect species richness. In this work, a new species of Hymenopteran parasitoid, Glyptapanteles gigas Liang & Song, sp. nov. found in Jinjiang within hosts of caterpillars Macrobrochis gigas (Lepidoptera: Arctiidae), is described and illustrated, with differences from similar species. Additionally, we presumed that both parasitoid and host species play very important role in the coevolution and tritrophic interaction between plants, phytophagous insects, and their parasitoids, because these insects probably broke the sporangia and made contributions to their colonization, or some spores were spread for long distances by adult moths after their emergence, or some parasitoids were attracted by the eggs and larvae of these caterpillars, which was also thought to be helpful to spread of spores.

Effect of SKF­96365 on cardiomyocyte hypertrophy induced by angiotensin II.

Angiotensin II (Ang II) is an important bioactive peptide in the renin­angiotensin system, and it can contribute to cell proliferation and cardiac hypertrophy. Dysfunctions in transient receptor potential canonical (TRPC) channels are involved in many types of cardiovascular diseases. The aim of the present study was to investigate the role of the TRPC channel inhibitor SKF­96365 in cardiomyocyte hypertrophy induced by Ang II and the potential mechanisms of SKF­96365. H9c2 cells were treated with different concentrations of Ang II. The expression levels of cardiomyocyte hypertrophy markers and TRPC channel­related proteins were also determined. The morphology and surface area of the H9c2 cells, the expression of hypertrophic markers and TRPC channel­related proteins and the [3H] leucine incorporation rate were detected in the Ang II­treated H9c2 cells following treatment with the TRPC channel inhibitor SKF­96365. The intracellular Ca2+ concentration was tested by flow cytometry. The present results suggested that the surface area of H9c2 cells treated with Ang II was significantly increased compared with untreated H9c2 cells. The fluorescence intensity of α­actinin, the expression of hypertrophic markers and TRPC­related proteins, the [3H] leucine incorporation rate and the intracellular Ca2+ concentration were all markedly increased in the Ang II­treated H9c2 cells but decreased following SKF­96365 treatment. The present results suggested that Ang II induced cardiomyocyte hypertrophy in H9c2 cells and that the TRPC pathway may be involved in this process. Therefore, SKF­96365 can inhibit cardiomyocyte hypertrophy induced by Ang II by suppressing the TRPC pathway. The present results indicated that TRPC may be a therapeutic target for the development of novel drugs to treat cardiac hypertrophy.

Synthesis and biological evaluation of 7-methoxy-1-(3,4,5-trimethoxyphenyl)-4,5-dihydro-2H-benzo[e]indazoles as new colchicine site inhibitors.

The colchicine site inhibitors (CSIs) displayed both antimitotic and vascular disrupting activities, therefore are promising potential antitumor agents. In this study, a series 1-phenyl-4,5-dihydro-2H-benzo[e]indazoles were found as new CSIs of which the bioactive configuration was locked. Among them, compounds C1 and C2 displayed the best activity, with tubulin polymerization IC50 of 3.4 and 1.5 µM, and growth IC50 of low nanomolar concentrations against human colon cancer cell lines. In addition, compound C1 showed excellent broad-spectrum antitumor activity in the NCI-60 Human Tumor Cell Lines Screen, encouraging further study of this antitumor compound.

1-Phenyl-dihydrobenzoindazoles as novel colchicine site inhibitors: Structural basis and antitumor efficacy.

The colchicine site inhibitors (CSIs) showed promising prospects as antitumor agents due to their vascular disrupting activities besides antimitotic activities. 1-Phenyl-dihydrobenzoindazole was found as a novel scaffold of CSI without the cis-trans isomerization problem. The X-ray co-crystal structure of the lead compound with tubulin was determined, which revealed the binding mode including special water-bridged hydrogen bonds. The structure also provided guidance for the structural optimization of this type of CSI, which led to the discovery of the most potent inhibitor A3, with growth IC50 lower than 1 nM against human colon cancer cell lines and tubulin polymerization IC50 of 1.6 µM. In addition, its water-soluble prodrug B1 showed good in vivo antitumor activity on two human colon cancer xenograft nude mice models, encouraging further study of this type of antitumor compound.

Downregulated miR-144-3p contributes to progression of lung adenocarcinoma through elevating the expression of EZH2.

OBJECTIVES: The intention of our study was to investigate the relationship between miR-144-3p and EZH2 as well as the effects of their interaction on cell propagation and invasiveness in lung adenocarcinoma (LUAD). METHODS: The expression levels of miR-144-3p and EZH2 in LUAD tissues and normal tissues were determined by qRT-PCR. The dual-luciferase reporter assay was utilized to validate the targeting relationship between miR-144-3p and EZH2. MTT assay and colony formation assay were performed to evaluate the viability and propagation of LUAD cells, while the effects of miR-144-3p and EZH2 on LUAD cell invasiveness were confirmed by transwell assay. Protein expression levels of VEGFA, MMP2, and MMP9 were measured by Western blot. Furthermore, xenograft tumor models were established to verify the effects of miR-144-3p on tumor formation and EZH2, VEGFA, MMP2 and MMP9 expressions in vivo. RESULTS: miR-144-3P was downregulated in LUAD tissues, and overexpression of miR-144-3p inhibited propagation and invasiveness of LUAD cells. EZH2 was a target of miR-144-3p and was highly expressed in LUAD cells. Knockdown of EZH2 could suppress the propagation and invasion of LUAD cells. Increased miR-144-3p expression exerted an inhibitory effect on LUAD tumor formation in vivo. CONCLUSION: Overexpression of miR-144-3p impeded the propagation and invasiveness of LUAD cells by targeting EZH2.

Upregulated lncRNA ADAMTS9-AS2 suppresses progression of lung cancer through inhibition of miR-223-3p and promotion of TGFBR3.

In this study, we aimed at investigating effects of lncRNA ADAMTS9-AS2 on lung cancer progression through regulating miR-223-3p and TGFBR3 expressions. Expressions of ADAMTS9-AS2 in lung cancer tissues and cell lines were determined by reverse transcriptase polymerase chain reaction (qRT-PCR). TargetScan and miRcode were used to predict the targeting relationships, respectively. The luciferase reporter system was used to verify that the relationship among ADAMTS9-AS2, TGFBR3 and miR-223-3p. Western blot assay tested the protein level changes in TGFBR3. Cell proliferation was determined by CCK-8 assay. Cell cycle and cell apoptosis were detected by flow cytometry assay, and migration and invasion were determined by transwell assay. Tumor xenograft model was developed to study the influence of ADAMTS9-AS2 on tumor growth in vivo. qRT-PCR results demonstrated that lncADAMTS9-AS2 was lowly expressed in lung cancer tissues. High expression of ADAMTS9-AS2 in lung cancer cells significantly reduced proliferation ability and inhibited migration, as well as elevating their apoptosis rate. In vivo assay found that ADAMTS9-AS2 suppressed the lung tumor growth. Bioinformatics predicted that miR-223-3p bound directly to the ADAMTS9-AS2 and TGFBR3, which was later confirmed by luciferase reporter system. ADAMTS9-AS2 transfection increased TGFBR3 mRNA and protein expressions in lung cancer cells, but miR-223-3p transfection significantly decreased them. Besides, our results showed that miR-223-3p induced cellular apoptosis while TGFBR3 group showed the complete opposite effect. It was proved that ADAMTS9-AS2 and TGFBR3 were the direct genes of miR-223-3p. MiR-223-3p promotes proliferation, migration and invasion of lung cancer cells by targeting TGFBR3. Therefore, ADAMTS9-AS2, miR-223-3p and TGFBR3 may provide potential targets for the treatment of lung cancer patients. © 2018 IUBMB Life, 70(6):536-546, 2018.

[Comparison between manual acupuncture and electroacupuncture for hot flashes and sex hormone of perimenopausal syndrome].

OBJECTIVE: To compare the effect and differences sex the influence of hormone levels of perimenopau-sal syndrome patients between manual acupuncture and electroacupuncture (EA). METHODS: A total of 50 cases with perimenopausal syndrome were randomly assigned into an manual acupuncture group (27 cases) and an EA group (23 cases), and 1 case dropped in the EA group. The acupoints in the two groups were Guanyuan (CV 4), Zigong (EX-CA 1), Tianshu (ST 25), and Sanyinjiao (SP 6). Acupuncture with 3-time small and even manipulation of lifting, thrusting and twirling was used in the acupuncture group, once 10 min. EA with sparse-dense wave and 10 Hz/50 Hz was applied in the EA group for 30 min. The treatments in the two groups were for continuous 8 weeks (24 times in total), once the other day, 3 times a week. The scores of 24-hour hot flashes even, menopausal rating scale (MRS) and menopause-specific quality of life questionnaire (MENQOL) were recorded before treatment and after 4-week and 8-week treatment, as well as 12 and 24 weeks after treatment. Serum sex hormone levels were tested before and after 8-week treatment as well as 12 weeks after treatment, including serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estracliol (E2). RESULTS: Compared with those before treatment, the 24-hour hot flashes even score, MRS and MENQOL scores were significantly lower after 4-week and 8-week treatments, 12 and 24 weeks after treatment (all P<0.05). All the above scores after 8-week treatment were lower than those after 4-week treatment (all P<0.05); and the scores 12 and 24 weeks after treatment were lower than those after 4-week and 8-week treatments (all P<0.05); all the scores after treatment were not significantly different at any time between the two groups (all P>0.05). Compared with those before treatment, serum FSH and E2 apparently improved in the two groups after 8-week treatment and 12 weeks after treatment (all P<0.05). LH levels did not significantly change in the two groups (all P>0.05). All the serum sex hormone levels showed no significant difference between the two groups (all P>0.05). CONCLUSIONS: Both acupuncture and EA can improve perimenopausal symptoms and serum sex hormone. The effects are similar.

Design, synthesis, and activity evaluation of selective inhibitors of anti-apoptotic Bcl-2 proteins: The effects on the selectivity of the P1 pockets in the active sites.

The anti-apoptotic Bcl-2 proteins are attractive targets for anti-cancer drug development, and the discovery of their selective inhibitors has become a research focus. In this Letter, obvious differences in the P1 pocket of the active site between Bcl-2, Bcl-xL, and Mcl-1 proteins were proposed by the structural comparison of these proteins. As a result, the groups in their inhibitors binding to the P1 pockets may have significant effect on the selectivity for these proteins. Based on this hypothesis, five types of derivatives of the lead compound B-1 were designed, and several highly selective inhibitors of Bcl-xL (E-1) or Mcl-1 proteins (G) were found. The selective inhibitors of Mcl-1 protein found in this Letter provide new structural types for the development of novel antitumor agents.

Structural modification of luteolin from Flos Chrysanthemi leads to increased tumor cell growth inhibitory activity.

The luteolin from Flos Chrysanthemi was found to directly bind to the Bcl-2 protein and inhibit the tumor cell growth in our previous study. However, it has been shown to possess wide and week biological activities. In this study, a series of derivatives of luteolin were designed and synthesized, and their tumor cell growth inhibitory activities were evaluated against human leukemia cell line HL-60. The results showed that compounds 1B-2, 2A-3, and 2B-5, with hydrophobic substituted benzyl groups introduced to B ring and hydrogen or methyl introduced to 7-OH group of luteolin, exhibited the strongest inhibitory activity with the IC50 lower than 10µM, which were significantly more potent than luteolin. The studies presented here offer a good example for modifications of flavones to improve their tumor cell growth inhibitory activities.

Discovery of benzenesulfonamide derivatives as potent PI3K/mTOR dual inhibitors with in vivo efficacies against hepatocellular carcinoma.

The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway is related to cellular activities. Abnormalities of this signaling pathway were discovered in various cancers, including hepatocellular carcinoma (HCC). The PI3K/mTOR dual inhibitors were proposed to have enhanced antitumor efficacies by targeting multiple points of the signaling pathway. We synthesized a series of propynyl-substituted benzenesulfonamide derivatives as PI3K/mTOR dual inhibitors. Compound 7k (NSC781406) was identified as a highly potent dual inhibitor, which exhibited potent tumor growth inhibition in the hepatocellular carcinoma BEL-7404 xenograft model. Compound 7k may be a potential therapeutic drug candidate for HCC.

Design, Synthesis and Biological Evaluation of 1,4-Disubstituted-3,4-dihydroisoquinoline Compounds as New Tubulin Polymerization Inhibitors.

A series of 1,4-disubstituted-3,4-dihydroisoquinoline derivatives designed as tubulin polymerization inhibitors were synthesized. Their cytotoxic activities against the CEM leukemia cell line were evaluated. Most of them displayed moderate cytotoxic activities, and compounds 21 and 32 showed good activities with IC50 of 4.10 and 0.64 µM, respectively. The most potent compound 32 was further confirmed to be able to inhibit tubulin polymerization, and its hypothetical binding mode with tubulin was obtained by molecular docking.