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Background: It has been reported that there are sex differences in plaque composition and hemodynamically significant stenosis. This study aimed to explore the impact of sex on cardiovascular risk factors for specific plaque compositions and hemodynamically significant stenosis., Methods: Data regarding demographics and cardiovascular risk factors were collected. Hemodynamically significant stenosis was identified by a computed tomography-derived fractional flow reserve of ≤ 0.8. Associations among cardiovascular risk factors, plaque composition, and hemodynamically significant stenosis were assessed using a multivariate binary logistic regression analysis across sexes. The discriminating capacity of diverse plaque components for hemodynamically significant stenosis was assessed by area under the receiver-operating characteristics curve with 95% confidence intervals., Results: A total of 1164 patients (489 men and 675 women) were included. For men, hyperlipidemia and cigarette smoking were risk factors for each plaque component (all P < 0.05), and diabetes mellitus also predicted fibrotic components (P < 0.05). For women, risk factors for each plaque component were hypertension and diabetes mellitus (all P < 0.01). Nonetheless, hyperlipidemia (P < 0.05) was a specific risk factor for non-calcified components. Calcified components combined with fibrotic components showed superior discrimination of hemodynamically significant stenosis in men and calcified components alone in women (all P < 0.01). Hypertension (P < 0.01) was a risk factor for hemodynamically significant stenosis in women. In contrast, diabetes, hyperlipidemia, and cigarette smoking were risk factors for hemodynamically significant stenosis in men (all P < 0.05)., Conclusions: In men, hemodynamically significant stenosis was predicted by a combination of calcified and fibrotic components with multiple risk factors. In women, hemodynamically significant stenosis was predicted by calcified components caused by a single risk factor. It might be a key point to improve prognosis by more precise risk management between men and women, which needs to be proved by further prospective trials., (© 2023. BioMed Central Ltd., part of Springer Nature.)

This study focused on the development and validation of a nutrition literacy assessment instrument for Chinese lactating women (NLAI-L). A comprehensive literature review and group discussion by experts in relevant fields were adopted to determine the dimension, topics and questions of NLAI-L. Content validity was evaluated by a panel of experts. The exploratory factor analyses (EFA) and confirmatory factor analyses (CFA) were used to evaluate the construct validity. Cronbach's α and split-half reliability were applied to examine the reliability of NLAI-L. The final NLAI-L consisted of 38 questions covering three dimensions: knowledge, behavior and skill. The EFA revealed four sub-domains for knowledge, one sub-domain for behavior and four sub-domains for skill. The results showed that NLAI-L had satisfactory content validity (CVI = 0.98, CVR = 0.96), good reliability (Cronbach's α coefficient = 0.84) and acceptable construct validity (χ 2 / df = 2.28, GFI = 2.81, AGFI = 0.79, RMSEA = 0.057). In the application part, the average NL score was 46.0 ± 9.3. In multivariate linear regression, education level, age, postnatal period and occupation were the potential influencing factors of NL for Chinese lactating women. The study established an effective and reliable assessment instrument for Chinese lactating women (NLAI-L) through qualitative and quantitative methods. The establishment of NLAI-L will provide an effective tool for exploring the role of NL in health or disease and provide a basis for the formulation of targeted nutrition interventions.

Two-dimensional graphdiyne (GDY) formed by sp and sp 2 hybridized carbon has been found to be an efficient toxic gas sensing material by density functional theory (DFT). However, little experimental research concerning its gas sensing capability has been reported owing to the complex preparation process and harsh experimental conditions. Herein, porous GDY nanosheets are successfully synthesized through a facile solvothermal synthesis technique by using CuO microspheres (MSs) as both template and source of catalyst. The porous GDY nanosheets exhibit a broadband optical absorption, rendering it suitable for the light-driven optoelectronic gas sensing applications. The GDY-based gas sensor was demonstrated to have excellent reversible to NO 2 behaviors at 25 °C for the first time. More importantly, higher response value and faster response-recovery time once exposed to NO 2 gas molecules are achieved by the illumination of UV light. In this way, our work paves the way for the exploration of GDY-based gas detection experimentally., (© 2023 Wiley-VCH GmbH.)

Chiral covalent organic frameworks (CCOFs) benefit from superior stability, abundant chiral environment, and homogeneous pore configuration. In its constructive tactics, only the post-modification method allows for the integration of supramolecular chiral selectors into achiral COFs. Here, the finding utilizes 6-deoxy-6-mercapto-β-cyclodextrin (SH-β-CD) as chiral subunits and 2,5-dihydroxy-1,4-benzenedicarboxaldehyde (DVA) as the platform molecule to synthesize chiral functional monomers through thiol-ene click reactions and directly establish ternary "pendant-type" SH-β-CD COFs. The chiral site density on SH-β-CD COFs was regulated by changing the proportion of chiral monomers to obtain an optimal construction strategy and remarkably improve the ability of chiral separation. SH-β-CD COFs were coated on the inner wall of the capillary in a covalently bound manner. The prepared open tubular capillary was achieved for the separation of six chiral drugs. By combining the outcomes of selective adsorption and chromatographic separation, we observed the higher density of chiral sites in the CCOFs, and poorer results were achieved. From the perspective of spatial conformational distribution, we interpret the variation in the performance of these chirality-controlled CCOFs for selective adsorption and chiral separation.

Objective: Fondaparinux is a synthetic anticoagulant for the prevention of venous thromboembolism (VTE), and its administration in Chinese cancer patients is rarely reported. This study aimed to assess the efficacy and safety of fondaparinux in preventing VTE in Chinese cancer patients., Methods: A total of 224 cancer patients who received fondaparinux treatment were reviewed in this single-arm, multicenter, retrospective study. Meanwhile, VTE, bleeding, death, and adverse events of those patients in the hospital and at 1 month after treatment (M1) were retrieved, respectively., Results: The in-hospital VTE rate was 0.45% and there was no (0.00%) VTE occurrence at M1. The in-hospital bleeding rate was 2.68%, among which the major bleeding rate was 2.23% and the minor bleeding rate was 0.45%. Moreover, the bleeding rate at M1 was 0.90%, among which both the major and minor bleeding rates were 0.45%. The in-hospital death rate was 0.45% and the death rate at M1 was 0.90%. Furthermore, the total rate of adverse events was 14.73%, including nausea and vomiting (3.13%), gastrointestinal reactions (2.23%), and reduced white blood cells (1.34%)., Conclusion: Fondaparinux could effectively prevent VTE with low bleeding risk and acceptable tolerance in cancer patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Su, Xie, Li, Pan, Xu, Chen and Cheng.)

As an important class of chemosensory-associated proteins, odorant binding proteins (OBPs) play a key role in the perception of olfactory signals for insects. Parasitoid wasp Microplitis mediator relies on its sensitive olfactory system to locate host larvae of Noctuidae and Geometridae. In the present study, MmedOBP14, a male-biased OBP in M. mediator, was functionally investigated. In fluorescence competitive binding assays, the recombinant MmedOBP14 showed strong binding abilities to five plant volatiles: β-ionone, 3,4-dimethylacetophenone, 4-ethylacetophenone, acetophenone and ocimene. Homology modeling and molecular docking results indicated that the binding sites of all five ligands were similar and concentrated in the binding pocket of MmedOBP14. Except acetophenone, the remaining four ligands at 1, 10 and 100 μg/μL caused strong antennal electrophysiological responses in adults M. mediator, and males showed more obvious EAG responses to most ligands than females. In behavioral trials, males were attracted by low concentrations of MmedOBP14 ligands, whereas high doses of β-ionone and acetophenone had a repellent effect on males. Moreover, 1 μg/μL of 3,4-dimethylacetophenone showed the strongest attractiveness to female wasps. These findings suggest that MmedOBP14 may play a more important role in the perception of plant volatiles for male wasps to locate habitat, supplement nutrition and search partners., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Ovarian cancer (OC) is a particularly lethal disease due to intratumoral heterogeneity, resistance to traditional chemotherapy, and poor response to targeted therapy and immunotherapy. Interferon-γ (IFN-γ) is an attractive therapeutic cytokine, with positive responses achieved in multiple OC clinical trials. However, clinical application of IFN-γ in OC is still hindered, due to the severe toxicity when used at higher levels, as well as the considerable pro-metastatic adverse effect when used at lower levels. Thus, an effective combined intervention is needed to enhance the anti-tumor efficacy of IFN-γ and to suppress the IFN-γ-induced metastasis. Here, we uncovered that OC cells develop an adaptive strategy by upregulating midkine (MDK) to counteract the IFN-γ-induced anti-tumor activity and to fuel IFN-γ-induced metastasis. We showed that MDK is a critical downstream target of IFN-γ in OC, and that this regulation acts in a dose-dependent manner and is mediated by STAT1. Gain-of-function studies showed that MDK overexpression promotes cell proliferation and metastasis in OC, indicating that IFN-γ-activated MDK may antagonize IFN-γ in inhibiting OC proliferation but synergize IFN-γ in promoting OC metastasis. Subsequently, we assessed the influence of MDK inhibition on IFN-γ-induced anti-proliferation and pro-metastasis effects using an MDK inhibitor (iMDK), and we found that MDK inhibition robustly enhanced IFN-γ-induced growth inhibition (all CIs < 0.1) and reversed IFN-γ-driven epithelial-to-mesenchymal transition (EMT) and metastasis in OC in vitro. Collectively, these data identify an IFN-γ responsive protein, MDK, in counteracting anti-proliferation while endowing the pro-metastatic role of IFN-γ in cancer treatment, and we therefore propose the combined utilization of the MDK inhibitor in IFN-γ-based therapies in future OC treatment.

IFN-γ is a pleiotropic cytokine with immunomodulatory and tumoricidal functions. It has been used as an anti-tumor agent in adjuvant therapies for various cancers. Paradoxically, recent advances have also demonstrated pro-tumorigenic effects of IFN-γ, especially in promoting cancer metastasis, with the mechanism remains unclear. This will undoubtedly hinder the application of IFN-γ in cancer treatment. Here, we verified that IFN-γ treatment led to activation of the epithelial-to-mesenchymal transition (EMT) programme and metastasis in cell lines of various cancers, including the kidney cancer cell line Caki-1, the lung cancer cell line A549, the cervical carcinoma cell line CaSki, the breast cancer cell line BT549 and the colon cancer cell line HCT116. We further disclosed that midkine (MDK), an emerging oncoprotein and EMT inducer, is a common responsive target of IFN-γ in these cell lines. Mechanistically, IFN-γ upregulated MDK via STAT1, a principle downstream effector in the IFN-γ signalling. MDK is elevated in the majority of cancer types in the TCGA database, and its overexpression drove EMT activation and cancer metastasis in all examined cell lines. Targeting MDK using a specific MDK inhibitor (iMDK) broadly reversed IFN-γ-activated EMT, and subsequently abrogated IFN-γ-triggered metastasis. Collectively, our data uncover a MDK-dependent EMT inducing mechanism underlying IFN-γ-driven metastasis across cancers which could be attenuated by pharmacological inhibition of MDK. Based on these findings, we propose that MDK may be used as a potential therapeutic target to eliminate IFN-γ-elicited pro-metastatic adverse effect, and that combined MDK utilization may expand the application of IFN-γ in cancer and improve the clinical benefits from IFN-γ-based therapies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zheng, Liu, Li, Chen, Tan, Li, Dong, Huang, Wen and Liu.)

Introduction: Lenvatinib is the first-line treatment for advanced hepatocellular carcinoma (HCC). We aimed to compare the clinical outcomes of lenvatinib plus drug-eluting beads transarterial chemoembolization (DEB-TACE) versus lenvatinib alone in real-world practice., Methods: This retrospective analysis included 142 consecutive patients who received lenvatinib plus DEB-TACE and 69 patients who received lenvatinib alone as first-line treatment from 15 Chinese academic centers from November 2018 to November 2019. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR) were evaluated by modified Response Evaluation Criteria in Solid Tumors criteria, and safety profiles were compared between the two groups., Results: The median OS and PFS were significantly longer in the combined therapy group than in the monotherapy group in whole cohort (median OS, 15.9 vs. 8.6 months, p = 0.0022; median PFS, 8.6 vs. 4.4 months, p < 0.001) and after propensity score matching analysis (median OS, 13.8 vs. 7.8 months, p = 0.03; median PFS, 7.8 vs. 4.5 months, p = 0.009). Moreover, the treatment option was an independent prognostic factor for OS and PFS with adjustment based upon baseline characteristics (adjusted hazard ratio [HR]: 0.53, 95% confidence interval [CI]: 0.36-0.78, p = 0.001, and adjusted HR: 0.42, 95% CI: 0.30-0.60, p < 0.001, respectively) and propensity score (adjusted HR: 0.52, 95% CI: 0.36-0.76, p = 0.001, and adjusted HR: 0.46, 95% CI: 0.33-0.64, p < 0.001, respectively). Moreover, a greater ORR was observed in the combined group (ORR: 46.48% vs. 13.05%, p < 0.001). Furthermore, the most common adverse events (AEs) were elevated aspartate aminotransferase (54.9%) and fatigue (46.4%) in the lenvatinib plus DEB-TACE group and lenvatinib group, respectively. Most AEs were mild-to-moderate and manageable., Conclusions: With well-tolerated safety, lenvatinib plus DEB-TACE was more effective than lenvatinib monotherapy in improving OS, PFS, and ORR. Thus, it may be a promising treatment for advanced HCC. Future prospective studies confirming these findings are warranted., (Copyright © 2022 by The Author(s). Published by S. Karger AG, Basel.)

Cisplatin (DDP) resistance is a huge obstacle to gastric cancer (GC) treatment. Long non-coding RNAs (lncRNAs) have been manifested to exert pivotal functions in GC development. Herein, we aimed to explore the functional impact of lncRNA small nucleolar RNA host gene 6 (SNHG6) on DDP resistance and progression of GC. Quantitative real-time PCR (qRT-PCR) assay or Western blotting was performed to detect the expression of SNHG6, microRNA(miR)-1297, and epithelial-mesenchymal transition (EMT)-related factors and B-Cell Lymphoma 2 (Bcl-2) in DDP-resistant GC cells. Half inhibition concentration (IC50) to DDP, clonogenicity, apoptosis and invasion were examined via CCK-8 assay, colony formation assay, flow cytometry and Transwell assay, respectively. Target association between miR-1297 and SNHG6 or BCL-2 was demonstrated via dual-luciferase reporter assay or RIP assay. Xenograft models in nude mice were formed to investigate role of SNHG6 in vivo. We found that SNHG6 and BCL-2 were up-regulated, while miR-1297 expression was declined in GC tissues and DDP-resistant cells. Moreover, depletion of SNHG6 or gain of miR-1297 could repress DDP resistance, proliferation and metastasis of DDP-resistant cells, which was weakened by miR-1297 inhibition or BCL-2 overexpression. Besides, SNHG6 positively regulated BCL-2 expression by sponging miR-1297. Furthermore, SNHG6 knockdown repressed GC tumor growth in vivo. In a word, lncRNA SNHG6 knockdown had inhibitory effects on DDP resistance and progression of GC by sponging miR-1297, highlighting its potential in GC treatment., (© 2021 The Author(s).)

Determining the etiology of end-stage renal disease (ESRD) constitutes a great challenge in the context of renal transplantation. Evidence is lacking on the genetic findings for adult renal transplant recipients through exome sequencing (ES). Adult patients on kidney transplant waitlist were recruited from 2017 to 2019. Trio-ES was conducted for the families who had multiple affected individuals with nephropathy or clinical suspicion of a genetic kidney disease owing to early onset or extrarenal features. Pathogenic variants were confirmed in 62 from 115 families post sequencing for 421 individuals including 195 health family members as potential living donors. Seventeen distinct genetic disorders were identified confirming the priori diagnosis in 33 (28.7%) families, modified or reclassified the clinical diagnosis in 27 (23.5%) families, and established a diagnosis in two families with ESRD of unknown etiology. In 14.8% of the families, we detected promising variants of uncertain significance in candidate genes associated with renal development or renal disease. Furthermore, we reported the secondary findings of oncogenes in 4.4% of the patients and known single-nucleotide polymorphisms associated with pharmacokinetics in our cohort to predict the drug levels of tacrolimus and mycophenolate. The diagnostic utility of the genetic findings has provided new clinical insight in most families that help with preplanned renal transplantation.

Purpose: The aim of the soft tissue reconstruction of plantar forefoot should yield weight-bearing function and aesthetic contour, which poses a significant challenge for reconstructive surgeons to provide an appropriate flap according to the "like for like" reconstructive principle. Local flaps and pedicled flaps have been described for the reconstruction of small- to medium-sized defects of plantar forefoot and achieved optimal results. However, reconstruction of extensive defects of plantar forefoot is rarely investigated. In this study, we present our experience using the free anterolateral thigh (ALT) flap in the reconstruction of extensive defects of plantar forefoot., Methods: Between November 2011 and April 2017, 9 patients were treated for extensive soft tissue defects in the plantar forefoot areas with ALT flaps. The mean age at the time of surgery was 39.3 years (range, 25-64 years)., Results: The follow-up period ranged from 12 to 77 months, with a mean of 31 months. All flaps survived well, and the patients were satisfied with the aesthetic and functional results. The size of the flaps ranged from 63 to 455 cm, with a mean of 197.7 cm. Seven patients with no bony involvement began to gradually weight-bear at 3 weeks postoperatively. During the follow-up time, postoperative ulceration at the reconstructed weight-bearing areas was not encountered., Conclusion: The ALT flap is a reliable option for treatment of extensive defects of plantar forefoot, resulting in an optimal functional and aesthetic outcome. Even when a total plantar loss exits, excellent results can be achieved.

The influences of maternal fine particulate matter (PM 2.5 ) exposure on intestinal oxidative stress, inflammation, tight junctions, and gut microbiota of offspring are not well understood. Moreover, research on the dietary intervention method has not been well studied. In our study, dams received PM 2.5 and quercetin intervention during gestation and lactation, and then inflammation biomarkers, oxidative stress indicators, tight junction proteins, and gut microbiota in the colon of offspring were analyzed. Compared with the control group, lower catalase (CAT) and superoxide dismutase (SOD) activities, higher interleukin-17A (IL-17A) and interleukin-22 (IL-22), decreased ZO-1 and occludin expressions, and higher Bacteroides abundance were observed in the offspring mice of the PM 2.5 group. However, higher CAT and SOD activities, lower IL-17A and IL-22 levels, increased ZO-1 and occludin expressions, and lower Bacteroides abundance were found in the quercetin groups. In addition, there was a negative correlation between Bacteroides abundance and CAT concentration. Additionally, Bacteroides abundance was positively related to IL-17A and IL-22 levels. These findings suggest that maternal PM 2.5 exposure may have some certain effects on intestinal oxidative stress, inflammation, and tight junctions. Quercetin administration may protect the offspring against these adverse effects. Changes of Bacteroides abundance play an important role in the process.

A potential mechanism for the global distribution of waterborne pathogens is through carriage by the migratory waterbirds. However, this mode of transmission has yet been confirmed epidemiologically. Here, we conducted whole genome sequencing of Vibrio spp. collected from waterbirds, sediments, and mollusks in the estuary of the Liaohe River in China to investigate this transmission mode. We found that a V. parahaemolyticus strain isolated from a waterbird was clonally related to the other V. parahaemolyticus strains obtained from the sediments and mollusks, and three V. mimicus strains isolated from bird feces were genomically related to those found in the mollusks and upstream groundwater, suggesting that the bird-carried Vibrio strains were acquired through the direct predation of the local mollusks. Surprisingly, two bird-carried V. parahaemolyticus strains belonging to the same clone were identified in Panjin and Shanghai, which are over 1,150 km apart, and another two were found at two locations 50 km apart, further supporting that waterbirds are capable of carrying and disseminating these pathogens over long distances. Our results provide the first evidence of direct transmission from mollusks to waterbirds and confirm that waterbirds act as disseminating vehicles of waterborne pathogens. Effective surveillance of migratory waterbirds along their routes will be valuable for predicting future epidemics of infectious diseases.

Short chain fatty acids (SCFAs) are produced by the colonic microbiota through fermentation. Influences of maternal PM 2.5 exposure on SCFAs of the offspring have not been well understood. Additionally, studies of dietary intervention have not been carried out yet. Here we performed a study that dams were received PM 2.5 and quercetin intervention during gestation and lactation. SCFAs in colon of dams and their offspring (on postnatal day 21 and 35) were analyzed using gas chromatography. For male offspring, when compared with the control group levels of acetic acid, butyric acid, and valeric acid were lower in the PM 2.5 group (p < 0.05), however, levels of isobutyric acid and isovaleric acid were higher in the PM 2.5 group (p < 0.05). For female offspring, as compared with the control group, propanoic acid was lower in the PM 2.5 group, however isovaleric acid was higher in the PM 2.5 group (p < 0.05). 100 mg/kg and 200 mg/kg quercetin intervention could inhibit SCFAs production of male offspring, especially in isobutyric acid and isovaleric acid (p < 0.05). 100 mg/kg quercetin intervention could upgrade the level of propanoic acid of female offspring (p < 0.05). Taken together, these results suggest that PM 2.5 tracheal exposure during gestation and lactation could influence SCFAs&nbsp;of offspring. Quercetin administration might have the potential to offset the effects of mater PM 2.5 exposure on SCFAs in the offspring to some extent. The above effects were showed in a sex-dependent manner., Competing Interests: The authors declare no conflict of interest.

A graphene oxide (GO)-nanoscale zerovalent iron (nZVI)-biochar composite (GO-nZVI/BC) was synthesized prior to characterization by X-ray diffraction (XRD), vibrating sample magnetometer (VSM), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), and Raman spectroscopy analyses. Batch experiments were performed at different initial Cr(VI) concentrations, contact times, and solution pH values. The effects of coexisting anions and chelating agents were also examined. The results indicated that the removal of Cr(VI) was highly pH-dependent and reached a maximum capacity at pH of 2. The equilibrium data were fitted well with the Langmuir isotherm model, and the kinetic data fitted better with the pseudo-second-order kinetic model. The increasing concentrations of EDTA in aqueous solutions were favorable to the removal of Cr(VI), while NO 3 - significantly inhibited adsorption. Furthermore, the GO-nZVI/BC maintained ~84.5% of its original capacity after aging in the air for 25 weeks. Based on the removal efficiency, GO-nZVI/BC can be considered to be an effective material for water treatment applications. PRACTITIONER POINTS: Biochar-supported graphene oxide-coated nanoscale zerovalent iron (GO-nZVI/BC) was synthesized and used to treat Cr(VI) from solution. Cr(VI) removal was pH-dependent and obeyed the Langmuir isotherm model and pseudo-second-order model. GO-nZVI/BC maintained ~84.5% of its original capacity after aging for 25 w in the air., (© 2019 Water Environment Federation.)

Gold nanoparticles (GNPs, 15 nm) were prepared and introduced to amino groups derived silica monolithic column. Bovine serum albumin (BSA) was immobilized via covalent modification method onto the carboxylic functionalized GNPs to afford chiral stationary phase (CSP) for enantioseparation. GNPs were well dispersed and successfully incorporated onto the columns with the contents as high as 17.18% by characterization method such as transmission electron microscopy (TEM), ultraviolet (UV)-visible absorption spectra and scanning electron microscopy (SEM). The preparation conditions of the BSA modified CSP were optimized and 10% (v/v) 3-aminopropyltriethoxysilane (APTES) and 15 g/L BSA were selected as appropriate reaction conditions. The enantioseparation performance of the BSA modified CSP has been investigated by capillary electrochromatography (CEC). Enantiomers of tryptophan, ephedrine and atenolol were resolved, and the baseline separation of tryptophan was achieved. Meanwhile, the influences of pH value, buffer concentrations and applied voltages used on the chiral separation were studied, and the optimal separation conditions were 10 mmol/L phosphate buffer at pH 7.4 and 15 kV applied voltages. In comparison with the BSA modified CSP prepared by physical adsorption, the CSP prepared by covalent modification method had better separation results, and the analytes could be separated directly without pre-column derivatization. In addition, the prepared BSA modified CSP exhibited good run to run repeatability with relative standard deviations (RSDs) of the migration times and selectivity factors not more than 2.3% and 0.96%, respectively. This work offers a good thinking for modification with other proteins or other types of chiral selectors.

Purpose: Methanol exposure have been shown to produce retinal abnormalities and visual dysfunctions in rodents and other mammals developing in utero . In this study, we characterized how methanol affects the retinal development in an ex utero embryonic system, the zebrafish., Methods: Zebrafish embryos were raised for 24 hours in fish water supplemented with various concentrations of methanol at 6 hours after fertilisation. The effects of methanol on retinal morphology were assessed by histologic and immunohistochemical analyses., Results: Zebrafish embryos exposed to moderate (3%) and high (4%) levels of methanol during early embryonic development had a small eye phenotype. Embryos exposed to high (4%) level of methanol had morphological abnormalities of the retinal pigment epithelia and the photoreceptors. Methanol exposure also caused inhibition of cell differentiation and proliferation in the retina at the early developmental stage., Conclusions: Low concentrations of methanol affect photoreceptor function but do not disturb retinal morphology. Higher levels of methanol exposure cause retinal patterning defects and a small eye phenotype., Competing Interests: None.

Twelve new limonoids (khasenegasins O-Z; 1 - 12 ) with three different kinds of skeletons, including eight mexicanolides, two gedunins, and two andirobins, together with four known limonoids ( 13 - 16 ) were isolated from the seeds of Khaya senegalensis . Their structures were determined by extensive spectroscopic analyses (HR-ESI-MS, 1D/2D NMR), and the absolute configurations of 1 and 2 were established by the electronic circular dichroism exciton chirality method. Moreover, a new andirobin-type limonoid ( 12 ) showed significant neuroprotective activity against glutamate-induced injury in primary rat cerebellar granule neuronal cells with increased viability of 83.3 ± 6.0 % at 10 µM and 80.3 ± 3.2 % at 1 µM., (Georg Thieme Verlag KG Stuttgart · New York.)

Regeneration and repair of peripheral nerve injury has always been a major problem in the clinic. The conventional technique based on suturing the nerve ends to each other coupled with the implantation of nerve conduits outside is associated with postoperative adhesions and scar problems. Recently, a novel biodegradable poly (DL-lactic acid) (PDLLA) film has been introduced. This novel anti-adhesion film has a porous structure with better mechanical properties, better flexibility, and more controllable degradation as compared to traditional non-porous nerve conduits. However, little is known about the effects of such PDLLA films on regeneration and repair of peripheral nerve injury in vivo. In this study, we evaluated the effects of PDLLA films implantation after sciatic nerve transection and anastomosis on subsequent sciatic nerve regeneration in vivo, using a rat sciatic nerve injury model. Sciatic nerve transection surgery coupled with direct suturing only, suturing and wrapping with traditional nerve conduits, or suturing and wrapping with PDLLA films was performed on adult Wistar rats. The additional wrapping with PDLLA films inhibited the nerve adhesion after 12 weeks recovery from surgery. It also increased the compound muscle action potentials and tibialis and gastrocnemius muscle wet weight ratio following 8 weeks recovery from surgery. Regenerated nerve fibers were relatively straight and the aligned structure was complete in rats with implantations of PDLLA films. The results suggested that PDLLA films can improve the nutritional status in the muscles innervated by the damaged nerves and promote nerve regeneration in vivo.