Mining key circRNA-associated-ceRNA networks for milk fat metabolism in cows with varying milk fat percentages.

BACKGROUND: Cow milk fat is an essential indicator for evaluating and measuring milk quality and cow performance. Growing research has identified the molecular functions of circular RNAs (circRNAs) necessary for mammary gland development and lactation in mammals. METHOD: The present study analyzed circRNA expression profiling data in mammary epithelial cells (MECs) from cows with highly variable milk fat percentage (MFP) using differential expression analysis and weighted gene co-expression network analysis (WGCNA). RESULTS: A total of 309 differentially expressed circRNAs (DE-circRNAs) were identified in the high and low MFP groups. WGCNA analysis revealed that the pink module was significantly associated with MFP (r = - 0.85, P = 0.007). Parental genes of circRNAs in this module were enriched mainly in lipid metabolism-related signaling pathways, such as focal adhesion, ECM-receptor interaction, adherens junction and AMPK. Finally, six DE-circRNAs were screened from the pink module: circ_0010571, circ_0007797, circ_0002746, circ_0003052, circ_0004319, and circ_0012840. Among them, circ_0002746, circ_0003052, circ_0004319, and circ_0012840 had circular structures and were highly expressed in mammary tissues. Subcellular localization revealed that these four DE-circRNAs may play a regulatory role in the mammary glands of dairy cows, mainly as competitive endogenous RNAs (ceRNAs). Seven hub target genes (GNB1, GNG2, PLCB1, PLCG1, ATP6V0C, NDUFS4, and PIGH) were obtained by constructing the regulatory network of their ceRNAs and then analyzed by CytoHubba and MCODE plugins in Cytoscape. Functional enrichment analysis revealed that these genes are crucial and most probable ceRNA regulators in milk fat metabolism. CONCLUSIONS: Our study identified several vital circRNAs and ceRNAs affecting milk fat synthesis, providing new research ideas and a theoretical basis for cow lactation, milk quality, and breed improvement.

Importance of habitat heterogeneity in tidal flats to the conservation of migratory shorebirds.

Understanding species distribution patterns and what determines them is critical for effective conservation planning and management. In the case of shorebirds migrating along the East Asian-Australasian Flyway (EAAF), the loss of stopover habitat in the Yellow Sea region is thought to be the primary reason for the precipitous population declines. However, the rates of decline vary considerably among species, and it remains unclear how such differences could arise within a group of closely related species using apparently similar habitats at the same locales. We mapped the spatial distributions of foraging shorebirds, as well as biotic (benthic invertebrates consumed by migrating shorebirds) and abiotic (sediment characteristics) environmental factors, at a key stopover site in eastern China. Five of the six sediment characteristics showed significant spatial variation with respect to distance along the shoreline or distance from the seawall in the same tidal flat. The biomasses of four of the six most abundant benthic invertebrates were concentrated in the upper or middle zones of the tidal flat. The distribution patterns of all three focal shorebird species on the tidal flat were best explained jointly by this heterogeneity of sediment characteristics and invertebrate prey. These results suggest that the loss of tidal flats along the Yellow Sea, which is typically concentrated at the upper and middle zones, may not only reduce the overall amount of staging habitat, but also disproportionately affect the most resource-rich portions for the birds. Effective conservation of shorebird staging areas along the EAAF and likely elsewhere must consider the subtle habitat heterogeneity that characterizes these tidal flats, prioritizing the protection of those portions richest in food resources, most frequently used by focal bird species, and most vulnerable to anthropogenic threats. Article impact statement: Heterogeneity of tidal flats with respect to biotic and abiotic factors must be considered in shorebird conservation planning.

Importancia de la heterogeneidad de hábitat en las llanuras intermareales para la conservación de aves playeras migratorias Resumen Entender las pautas de distribución de las especies y los factores que las determinan es fundamental para planificar y gestionar eficazmente su conservación. En el caso de las aves playeras que migran a lo largo de la ruta migratoria Asia Oriental-Australasia (EAAF, en inglés), se cree que la pérdida de puntos de parada en la región del Mar Amarillo es la razón principal de la declinación poblacional precipitada. Sin embargo, las tasas de declinación varían considerablemente entre especies, y sigue sin estar claro cómo pueden surgir tales diferencias dentro de un grupo de especies emparentadas que utilizan hábitats aparentemente similares en los mismos lugares. Mapeamos las distribuciones espaciales de las aves playeras forrajeras, así como los factores ambientales bióticos (invertebrados bénticos consumidos por las aves playeras migratorias) y abióticos (características de los sedimentos), en un punto de parada clave en el este de China. Cinco de las seis características de los sedimentos mostraron una variación espacial significativa con respecto a los cambios lineales en la distancia a lo largo de la costa o la distancia desde el malecón en la misma llanura mareal. La biomasa de cuatro de los seis invertebrados bénticos más abundantes se concentró en las zonas superior o media de la llanura mareal. Esta heterogeneidad de las características de los sedimentos y de las presas invertebradas es la que mejor explica los patrones de distribución de las tres especies de aves playeras en la llanura mareal. Estos resultados sugieren que la pérdida de llanuras mareales a lo largo del Mar Amarillo, que suele concentrarse en las zonas superior y media, puede no sólo reducir la cantidad total de hábitat de parada, sino también afectar de manera desproporcionada a las partes más ricas en recursos para las aves. La conservación eficaz de los puntos de parada de las aves playeras a lo largo del EAAF, y probablemente en otros lugares, debe tener en cuenta la sutil heterogeneidad del hábitat que caracteriza a estas llanuras mareales, priorizando la protección de las partes más ricas en recursos alimenticios, más frecuentemente utilizadas por las especies de aves focales y más vulnerables a las amenazas antropogénicas.

Assessing shorebird mortalities due to razor clam aquaculture at key migratory stopover sites in southeastern China.

Aquaculture can provide foraging habitat for birds, but it can also result in intentional and accidental mortality. We examined an overlooked conflict between razor clam (Sinonovacula spp.) aquaculture and declining shorebirds in southeastern China's Fujian and Zhejiang provinces. We surveyed 6 out of 11 internationally important stopover sites for these shorebirds and monitored shorebird mortality in 2 sites (Xinghua Bay, Yueqing Bay) with razor clam aquaculture. We visited an additional 32 sites in these 2 provinces to determine if there was netting in other razor clam farms. Approximately 8-9 km2 of intertidal foraging habitat was covered by horizontal nets to prevent birds from feeding on young razor clams at Xinghua Bay and Yueqing Bay. We conservatively estimated that 13,676 (2.5th-97.5th percentile 8,330-21,285) individual shorebirds were entangled in the nets at the 2 monitored sites in April and May 2021, including 2 endangered and 7 near-threatened species. Mortality of 5 species for which we had sufficient data accounted for 0.76% (black-tailed godwit [Limosa limosa]) to 4.27% (terek sandpiper [Xenus cinereus]) of their total flyway populations. This level of mortality could strongly affect their populations. We found netting at 17 additional razor clam farms, indicating a widespread threat to shorebirds. Although razor clams are typically harvested in late March to early April, nets are left on the mudflats throughout the spring and summer, including when the bulk of shorebird migration takes place. Immediately removing these nets after the clam harvest could prevent most of the spring mortality of shorebirds, although this is unlikely to happen without government regulations or economic incentives. To better assess and mitigate the impacts of this conflict, future research should quantify shorebird mortality at other razor clam farms, including during winter, explore less harmful deterrence methods, and assess the socioeconomic factors driving the conflict.

Evaluación de la mortalidad de aves costeras causada por la acuacultura de almejas navaja en sitios importantes de descanso migratorio en el sureste de China Resumen La acuacultura puede proporcionar hábitats de forrajeo para las aves, pero también puede derivar en muertes accidentales o intencionales. Analizamos un conflicto ignorado entre la acuacultura de almeja navaja (Sinonovacula spp.) y la declinación de aves costeras en las provincias de Fujian y Zhejiang del sureste de China. Censamos seis de los once sitios de descanso con importancia internacional para estas aves y monitoreamos su mortalidad en dos sitios en donde se cría la almeja navaja: la bahía de Xinghua y la de Yueqing. Además, visitamos 32 sitios en estas dos provincias para determinar si existían redes en otras granjas de almeja navaja. Unos 8 ­ 9 km2 del hábitat intermareal de forrajeo estaban cubiertos por redes horizontales para evitar que las aves se alimentaran de las almejas juveniles en ambas bahías. Estimamos moderadamente que 13,676 (2.5° ­ 97.5° percentil 8,330 ­ 21,285) individuos de aves costeras se enredaron en las redes en los dos sitios monitoreados durante abril y mayo de 2021, incluyendo a dos especies en peligro y siete casi amenazadas. La mortalidad de las cinco especies para las cuales tuvimos suficientes datos representó del 0.76% (Limosa limosa) al 4.27% (Xenus cinereus) del total de las poblaciones migratorias. Este nivel de mortalidad podría tener un gran efecto sobre las poblaciones de estas especies. Encontramos redes en 17 granjas más, lo que indica una amenaza extendida para las aves costeras. Aunque es típico que se colecte la almeja navaja a finales de marzo y principios de abril, las redes permanecen durante toda la primavera y el verano, incluso cuando ocurre la mayoría de los vuelos migratorios. La eliminación inmediata de estas redes después de la colecta de almejas podría prevenir la mayoría de las muertes primaverales de las aves costeras, aunque no es probable que esto suceda sin regulaciones gubernamentales o incentivos económicos. Para tener mejores evaluaciones y mitigaciones del impacto de este conflicto, una investigación más profunda debería cuantificar la mortalidad de las aves costeras en otras granjas, incluso durante el invierno, explorar métodos de disuasión menos dañinos y evaluar los factores socioeconómicos que causan el conflicto.

First record of the genus Schizothorax in rivers of the Central Himalayas in China.

A total of 40 specimens of the genus Schizothorax (Cyprinidae: Schizothoracinae), including 10 matured males, 19 matured females and 11 juveniles, were captured from the Kirong Tsangpo River in China, which is located in the southern slope of the Central Himalayas. These specimens are identified as Schizothorax richardsonii (Grey, 1832) based on morphological characters and molecular analyses using mitochondrial Cyt b gene sequences. The Kirong population of S. richardsonii is relatively isolated from other populations in the Himalayas and has low genetic diversity. This is the first record of the genus Schizothorax fish in rivers of the Central Himalayas in China. As S. richardsonii is a vulnerable species on the IUCN Red List, a protection plan should be conducted to reduce the impact of anthropogenic disturbance by monitoring the natural population dynamics and assessing the ecological determinants of its distribution.

Enantioselective Synthesis of Planar-Chiral Sulfur-Containing Cyclophanes by Chiral Sulfide Catalyzed Electrophilic Sulfenylation of Arenes.

An efficient catalytic asymmetric electrophilic sulfenylation reaction for the synthesis of planar-chiral sulfur-containing cyclophanes has been developed for the first time. This was achieved by using a new Lewis base catalyst and a new ortho-trifluoromethyl-substituted sulfenylating reagent. Using the substrates with low rotational energy barrier, the transformation proceeded through a dynamic kinetic resolution, and the high rotational energy barrier of the substrates allowed the reaction to undergo a kinetic resolution process. Meanwhile, this transformation was compatible with a desymmetrization process when the symmetric substrates were used. Various planar-chiral sulfur-containing cyclophanes were readily obtained in moderate to excellent yields with moderate to excellent enantioselectivities (up to 97 % yield and 95 % ee). This approach was used to synthesize pharmaceutically relevant planar-chiral sulfur-containing molecules. Density functional theory calculations showed that π-π interactions between the sulfenyl group and the aromatic ring in the substrate play a crucial role in enantioinduction in this sulfenylation reaction.

The effect of thionation of the carbonyl group on the photophysics of compact spiro rhodamine-naphthalimide electron donor-acceptor dyads: intersystem crossing, charge separation, and electron spin dynamics.

Herein, a spiro rhodamine (Rho)-thionated naphthalimide (NIS) electron donor-acceptor orthogonal dyad (Rho-NIS) was prepared to study the formation of a long-lived charge separation (CS) state via the electron spin control approach. The transient absorption (TA) spectra of Rho-NIS indicated that the intersystem crossing (ISC) occurs within 7-42 ps to produce the 3NIS state via the spin orbit coupling ISC (SOC-ISC). The energy order of 3CS (2.01 eV in n-hexane, HEX) and 3LE states (1.68 eV in HEX) depended on the solvent polarity. The 3NIS state having n-π* character and a lifetime of 0.38 µs was observed for Rho-NIS in toluene (TOL). Alternatively, in acetonitrile (ACN), the long-lived 3CS state (0.21 µs) with a high CS state quantum yield (ΦCS, 97%) was produced with the 3NIS state as the precursor and the CS took 134 ps. On the contrary, in the case of the reference Rho-naphthalimide (NI) Rho-NI dyad without thionation of its carbonyl group, a long-lived CS state (0.94 µs) with a high energy level (ECS = 2.12 eV) was generated even in HEX with a lower ΦCS (49%). In the presence of an acid, the Rho unit in the Rho-NIS adopted an open form (Rho-o) and the 3NIS state was produced within 24-47 ps with the 1Rho-o state as the precursor. Subsequently, slow intramolecular triplet-triplet energy transfer (TTET, 0.11-0.60 µs) produced the 3Rho-o state (9.4-13.6 µs). According to the time-resolved electron paramagnetic resonance (TREPR) spectra of NIS-NH2, the zero-field splitting (ZFS) parameter |D| and E of the triplet state were determined to be 6165 MHz and -1233 MHz, respectively, indicating that its triplet state has significant nπ* character, which was supported by its short triplet state lifetime (6.1 µs).

Identification of critical lncRNAs for milk fat metabolism in dairy cows using WGCNA and the construction of a ceRNAs network.

As key regulators, long non-coding RNAs (lncRNAs) play a crucial role in the ruminant mammary gland. However, the function of lncRNAs in milk fat synthesis from dairy cows is largely unknown. In this study, we used the weighted gene co-expression network analysis (WGCNA) to comprehensive analyze the expression profile data of lncRNAs from the group's previous Illumina PE150 sequencing results based on bovine mammary epithelial cells from high- and low-milk-fat-percentage (MFP) cows, and identify core_lncRNAs significantly associated with MFP by module membership (MM) and gene significance (GS). Functional enrichment analysis (Gene Ontology, Kyoto Encyclopedia of Genes and Genomes) of core_lncRNA target genes (co-localization and co-expression) was performed to screen potential lncRNAs regulating milk fat metabolism and further construct an interactive regulatory network of lipid metabolism-related competing endogenous RNAs (ceRNAs). A total of 4876 lncRNAs were used to construct the WGCNA. The MEdarkturquoise module among the 19 modules obtained was significantly associated with MFP (r = 0.78, p-value <0.05) and contained 64 core_lncRNAs (MM > 0.8, GS > 0.4). Twenty-four lipid metabolism-related lncRNAs were identified by core_lncRNA target gene enrichment analysis. TCONS_00054233, TCONS_00152292, TCONS_00048619, TCONS_00033839, TCONS_00153791 and TCONS_00074642 were key candidate lncRNAs for regulating milk fat synthesis. The 22 ceRNAs most likely to be involved in milk fat metabolism were constructed by interaction network analysis, and TCONS_00133813 and bta-miR-2454-5p were located at the network's core. TCONS_00133813_bta-miR-2454-5p_TNFAIP3, TCONS_00133813_bta-miR-2454-5p_ARRB1 and TCONS_00133813_bta-miR-2454-5p_PIK3R1 are key candidate ceRNAs associated with milk fat metabolism. This study provides a framework for the co-expression module of MFP-related lncRNAs in ruminants, identifies several major lncRNAs and ceRNAs that influence milk fat synthesis, and provides a new understanding of the complex biology of milk fat synthesis in dairy cows.

A dynamic physical-distancing model to evaluate spatial measures for prevention of Covid-19 spread.

Motivated by the global pandemic of COVID-19, this study investigates the spatial factors influencing physical distancing, and how these affect the transmission of the SARS-CoV-2 virus, by integrating pedestrian dynamics with a modified susceptible-exposed-infectious model. Contacts between infected and susceptible pedestrians are examined by determining physical-distancing pedestrian dynamics in three types of spaces, and used to estimate the proportion of newly infected pedestrians in these spaces. Desired behaviour for physical distancing can be observed from simulation results, and aggregated simulation findings reveal that certain layouts enable physical distancing to reduce the transmission of SARS-CoV-2. We also provide policymakers with several design guidelines on how to proactively design more effective and resilient space layouts in the context of pandemics to keep low transmission risks while maintaining a high pedestrian volume. This approach has enormous application potential for other infectious-disease transmission and space assessments.

Hepatic stellate cells specific liposomes with the Toll-like receptor 4 shRNA attenuates liver fibrosis.

The hepatic stellate cells (HSCs) play a significant role in the onset of liver fibrosis, which can be treated by the inhibition and reversal of HSC activation. The RNA interference-mediated TLR4 gene silencing might be a potential therapeutic approach for liver fibrosis. The crucial challenge in this method is the absence of an efficient delivery system for the RNAi introduction in the target cells. HSCs have an enhanced capacity of vitamin A intake as they contain retinoic acid receptors (RARs). In the current study, we developed cationic liposomes modified with vitamin A to improve the specificity of delivery vehicles for HSCs. The outcome of this study revealed that the VitA-coupled cationic liposomes delivered the TLR4 shRNA to aHSCs more efficiently, as compared to the uncoupled cationic liposomes, both in the in vitro and in vivo conditions. Besides, as evident from the outcome of this study, the TLR4 gene silencing inhibited the HSCs activation and attenuated the liver fibrosis via the NF-κB transcriptional inactivation, pro-inflammatory cytokines secretion and reactive oxygen species (ROS) synthesis. Thus, the VitA-coupled liposomes encapsulated with the TLR4-shRNA might prove as an efficient therapeutic agent for liver fibrosis.

Simultaneous determination of Acetaminophen and dopamine based on a water-soluble pillar[6]arene and ultrafine Pd nanoparticle-modified covalent organic framework nanocomposite.

While numerous sensing strategies have been applied in the determination of Acetaminophen (AP), dopamine (DA), and ascorbic acid (AA), the selectivity is always a critical challenge based on their similar structure and function. Accordingly, the development of a highly selective sensing method is not only necessary but also crucial. In this study, a novel electrochemical sensing platform for the simultaneous determination of AP and DA has been successfully constructed based on a multifunctional nanocomposite (WP6-Pd-COF) of water-soluble pillar[6]arene (WP6), ultrafine Pd nanoparticles, and triethylene glycol-modified covalent organic framework (COF). Pd nanoparticles with an average size of 4.2 nm are prepared by reducing K2PdCl4 under the stabilization of oxygen-rich COF, which shows superior catalytic activity in electrochemical detection. A supramolecular host-guest recognition system introduced between WP6 and analytes (AP, DA, and AA) can effectively recognize AP and DA, implying the simultaneous determination of AP and DA by this approach. The electrode, best operated at a working potential range from -0.2 to 0.8 V (vs. Hg/Hg2Cl2), works in the concentration ranges of 0.2-8 µM for DA and 0.1-7.5 µM for AP, and has a detection limit of 0.06 µM for DA and 0.03 µM for AP (S/N = 3). Therefore, this study presents potential application values in sensing, catalysis, and other fields.

Decreased mortality seen in rifampicin/multidrug-resistant tuberculous meningitis treated with linezolid in Shenzhen, China.

BACKGROUND: The morbidity of rifampicin/multidrug-resistant tuberculous meningitis (RR/MDR-TBM) has shown an increasing trend globally. Its mortality rate is significantly higher than that of non-rifampicin/multidrug-resistant tuberculous meningitis (NRR/MDR-TBM). This article aimed to explore risk factors related to RR/MDR-TBM, and compare therapeutic effects of linezolid (LZD)- and non-linezolid-containing regimen for RR/MDR-TB patients in Shenzhen city. Furthermore, we aimed to find a better therapy for pathogen-negative TBM with RR/MDR-TBM related risk factors. METHODS: We conducted a retrospective study enrolling 137 hospitalized cases with confirmed TBM from June 2014 to March 2020. All patients were divided into RR/MDR-TBM group (12 cases) and NRR/MDR-TBM group (125 cases) based on GeneXpert MTB/RIF and (or) phenotypic drug susceptibility test results using cerebral spinal fluid (CSF). The risk factors related to RR/MDR-TBM were investigated through comparing clinical and examination features between the two groups. The mortality rate of RR/MDR-TBM patients treated with different regimens was analyzed to compare their respective therapeutic effects. A difference of P < 0.05 was considered statistically significant. RESULTS: Most patients (111/137, 81%) were from southern or southwestern China, and a large proportion (72/137, 52.55%) belonged to migrant workers. 12 cases were RR/MDR-TBM (12/137, 8.8%) while 125 cases were NRR/MDR-TBM (125/137, 91.2%). The proportion of patients having prior TB treatment history in the RR/MDR-TBM group was significantly higher than that of the NRR/MDR-TBM group (6/12 vs. 12/125, 50% vs. 10.5%, P < 0.01). No significant difference was observed on other clinical and examination features between the two groups. Mortality was significantly lower in RR/MDR-TBM patients on linezolid-containing treatment regimen than those who were not (0/7 versus 3/5, 0% versus 60%, P = 0.045). CONCLUSIONS: The main related risk factor of RR/MDR-TBM is the history of anti-tuberculosis treatment. Linezolid-containing regimen appears to lower mortality rate of RR/MDR-TBM significantly in our study. We think Linezolid should be evaluated prospectively in the treatment of RR/MDR-TBM.

Expression of eosinophil in peripheral blood of patients with COVID-19 and its clinical significance.

AIMS: To investigate the eosinophil cell (EC) expression in peripheral blood of patients infected with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) and its clinical significance of diagnosis and prognosis. METHODS: 95 patients, whose nucleic acid test of SARS-CoV-2 was positive to make a definite diagnosis of COVID-19, were selected as the study group. They were admitted at the Chengdu Public Health Clinical Medical Center from January 21 to March 2, 2020. Another 95 healthy subjects and 95 non-infectious fever patients during the same period were selected as the control group. The BC-6900 blood cell analyzer was used to continuously observe and detect ECs in 95 patients with COVID-19 and the control group. The differences in expression levels of ECs in peripheral blood were analyzed. RESULTS: ECs were significantly decreased in 95 (75.8%) COVID-19 patients (P < .01). The absolute EC count IQR was 0.01 × 109/L (0 × 109/L - 0.04 × 109/L), and the EC percentage IQR was 0.3% (0.1% - 0.8%). As the patients' condition improved, the ECs returned to normal, but for those without improvement, ECs continued to decline. CONCLUSIONS: ECs decreased remarkably in patients with COVID-19, and gradually returned to normal after the improvement of the patients' condition, while EC continued to decrease in patients without improvement. It is suggested that ECs have certain clinical significance in the diagnosis and prognosis of COVID-19, and may be a useful index in the early warning of acute infectious diseases.

Integrating transcriptomes and somatic mutations to identify RNA methylation regulators as a prognostic marker in hepatocellular carcinoma.

BACKGROUND: RNA methylation modifying plays an important role in the occurrence and progression of a range of human cancers including hepatocellular carcinoma (HCC), which is characterized by a mass of genetic and epigenetic alterations. However, the treatment targeting these alterations is limited. METHODS: We used comprehensive bioinformatics analysis to analyze the correlation between cancer-associated RNA methylation regulators and HCC malignant features in network datasets. RESULTS: We identified two HCC subgroups (cluster 1 and 2), which had clearly distinct clinicopathological, biofunctional and prognostic characteristics, by consensus clustering. The cluster 2 subgroup correlated with malignancy of the primary tumor, higher tumor stage, higher histopathological grade and higher frequency of TP53 mutation, as well as with shorter survival when compared with cluster 1. Gene enrichment indicated that the cluster 2 correlated to the tumor malignancy signaling and biological processes. Based on these findings, an 11-gene risk signature was built, which not only was an independent prognostic marker but also had an excellent power to predict the tumor features. CONCLUSIONS: Our study indicated that RNA methylation regulators are vital for HCC malignant progression and provide an important evidence for RNA methylation, methylation regulators are actionable targets for anticancer drug discovery.

Facile Synthesis of Saikosaponins.

Saikosaponin A (SSa) and D (SSd) are typical oleanane-type saponins featuring a unique 13,28-epoxy-ether moiety at D ring of the aglycones, which exhibit a wide range of biological and pharmacological activities. Herein, we report the first synthesis of saikosaponin A/D (1-2) and their natural congeners, including prosaikosaponin F (3), G (4), saikosaponin Y (5), prosaikogenin (6), and clinoposaponin I (7). The present synthesis features ready preparation of the aglycones of high oxidation state from oleanolic acid, regioselective glycosylation to construct the ß-(1→3)-linked disaccharide fragment, and efficient gold(I)-catalyzed glycosylation to install the glycans on to the aglycones.

Upper tidal flats are disproportionately important for the conservation of migratory shorebirds.

Migratory animals play vital ecological roles in ecosystems worldwide, yet many species are threatened by human activities. Understanding the detailed patterns of habitat use throughout the migration cycle is critical to developing effective conservation strategies for these species. Migratory shorebirds undertake some of the longest known migrations, but they are also declining precipitously worldwide. To better understand the dynamics of shorebird declines along the East Asian-Australasian Flyway, we quantified the spatiotemporal foraging distribution of 17 migratory shorebirds at two critical stopover sites. We found that shorebirds exhibit substantial interspecific and site-specific differences in their foraging distributions. Notwithstanding these differences, however, the upper tidal flats appear to be especially important to most shorebirds by providing more than 70% of the birds' cumulative foraging time, twofold greater than their proportional area. Because the upper tidal flats are also more prone to coastal development, our findings may help to explain why shorebird populations along the flyway have declined much faster than the overall rate of tidal flat loss. Our work highlights the importance of protecting upper tidal flats to conserve migratory shorebirds and demonstrates the value of a detailed ecological understanding of habitat usage by migratory animals for conservation planning.

FABP7 is a potential biomarker to predict response to neoadjuvant chemotherapy for breast cancer.

BACKGROUND: Early prediction of response to neoadjuvant chemotherapy (NAC) is critical in choosing appropriate chemotherapeutic regimen for patients with locally advanced breast cancer. Herein, we sought to identify potential biomarkers to predict the response to neoadjuvant chemotherapy for breast cancer patients. METHODS: Three genomic profiles acquired by microarray analysis from subjects with or without residual tumors after NAC downloaded from the GEO database were used to screen the differentially expressed genes (DEGs). An array of public databases, including ONCOMINE, cBioportal, Breast Cancer Gene Expression Miner v4.0, and the Kaplan Meir-plotter, etc., were used to evaluate the potential functions, related signaling pathway, as well as prognostic values of FABP7 in breast cancer. Anti-cancer drug sensitivity assay, real-time PCR, flow cytometry and western-blotting assays were used to investigate the function of FABP7 in breast cancer cells and examine the relevant mechanism. RESULTS: Two differentially expressed genes, including FABP7 and ESR1, were identified to be potential indicators of response to anthracycline and taxanes for breast cancer. FABP7 was associated with better chemotherapeutic response, while ESR1 was associated with poorer chemotherapeutic effectiveness. Generally, the expression of FABP7 was significantly lower in breast cancer than normal tissue samples. FABP7 mainly high expressed in ER-negative breast tumor and might regulate cell cycle to enhance chemosensitivity. Moreover, elevated FABP7 expression increased the percentage of cells at both S and G2/M phase in MDA-MB-231-ADR cells, and decreased the percentage of cells at G0/G1 phase, as compared to control group. Western-blotting results showed that elevated FABP7 expression could increase Skp2 expression, while decrease Cdh1 and p27kip1 expression in MDA-MB-231-ADR cells. In addition, FABP7 was correlated to longer recurrence-free survival (RFS) in BC patients with ER-negative subtype of BC treated with chemotherapy. CONCLUSION: FABP7 is a potential favorable biomarker and predicts better response to NAC in breast cancer patients. Future study on the predictive value and detail molecular mechanisms of FABP7 in contribution to chemosensitivity in breast cancer is warranted.

Pediatric dermatology-Critical approach to the new treatments.

The field of pediatric dermatology treatment has been rich in new developments. Several recent therapeutic advances in pediatric dermatology have been made. This review will focus on critical approach to the new treatments for several entities encountered in pediatric dermatology. The use of biologics and small molecules in children with atopic dermatitis and psoriasis, exciting advances in the use of propranolol and other beta-blockers for the treatment of infantile hemangiomas, the use of sirolimus for vascular anomalies will be discussed.

Total Synthesis of Aplysiasecosterol A.

Aplysiasecosterol A (1) is a structurally unusual 9,11-secosteroid isolated from the sea hare Aplysia kurodai. We have accomplished the first and asymmetric total synthesis of 1 in a convergent fashion. The left-hand segment bearing three adjacent stereocenters was constructed through desymmetrizing reduction, ketalization, and radical cyclization. A strategy of asymmetric 2-bromoallylation followed by spontaneous desymmetrizing lactolization enabled a more expeditious access to this segment. The right-hand segment was prepared through two different approaches: one featuring Myers alkylation and Suzuki-Miyaura coupling and the other relying upon Aggarwal lithiation-borylation and Zweifel-Evans olefination. The two fragments were coupled by a Reformatsky type reaction. The three consecutive stereocenters embedded in the central domain of 1 were generated by an iron-mediated, hydrogen atom transfer based radical cyclization reaction.

Simultaneous structural identification of diacylglyceryl-N-trimethylhomoserine (DGTS) and diacylglycerylhydroxymethyl-N,N,N-trimethyl-ß-alanine (DGTA) in microalgae using dual Li+ /H+ adduct ion mode by ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry.

RATIONALE: Diacylgycerol-N-trimethylhomoserine (DGTS) and diacylglycerylhydroxymethyl-N,N,N-trimethyl-ß-alanine (DGTA) are structural isomers that are the most commonly described betaine lipids in microalgae. The structural differentiation and precise identification of DGTS and DGTA in microalgae need to be established during mass spectrometry analysis. METHODS: Total lipid was extracted from Amphora spp. with CHCl3 /CH3 OH (1:1, v/v). The qualitative analysis of DGTS and DGTA in Amphora spp. was carried out using Li+ /H+ dual mode by ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry operating in MSE mode (UPLC/QTOF MSE ). RESULTS: Characteristic fragment ions [C10 H22 O5 N]+ at m/z 236.15 and [C7 H14 O2 N]+ at m/z 144.10 from the [M + H]+ precursor ion can be used for the qualitative analysis of both DGTA and DGTS, whereas the loss of m/z 87 and 74 from the [M + Li]+ precursor ion are specific for DGTS, and the loss of m/z 103 from the [M + Li]+ precursor ion is only for DGTA. As a result, 9 DGTSs and 16 DGTAs with different fatty acids were identified simultaneously in Amphora spp. Semi-quantitative analysis of DGTS and DGTA in Amphora spp. showed that the contents of DGTS ranged from 0.003 to 0.438 nmol mg-1 dw, and that of DGTA from 0.004 to 0.414 nmol mg-1 dw. CONCLUSIONS: This is the first report to achieve the ambiguous structural identification of DGTS and DGTA by UPLC/QTOF MSE using dual Li+ /H+ adduct ion mode, which has remained a challenge in the past. It could provide new insights into their phylogeny and be helpful to characterize the natural phytoplankton communities as intact polar lipid biomarkers. Copyright © 2017 John Wiley & Sons, Ltd.

Novel naphtho[2,1-d]oxazole-4,5-diones as NQO1 substrates with improved aqueous solubility: Design, synthesis, and in vivo antitumor evaluation.

A new series of ortho-naphthoquinone analogs of ß-lapachone were designed, synthesized and evaluated. The biological results indicated that most of our compounds were efficient substrates for NQO1. The new scaffold with water-soluble side chain resulted in greater solubility under acidic condition compared to ß-lapachone. Thus avoiding the use of hydroxylpropyl ß-cyclodextrin which would finally cause the rapid drug clearance from the blood and dose-limiting toxicity in the form of hemolytic anemia. The most soluble and promising compound in this series was 2-((4-benzylpiperazin-1-yl)methyl)naphtho[2,1-d]oxazole-4,5-dione (3k), which inhibited cancer cell (NQO1-rich A549 cell line) growth at IC50 values of 4.6±1.0µmol·L(-1). Furthermore, compound 3k had in vivo antitumor activity in an A549 tumor xenografts mouse model comparable to the activity obtained with ß-lapachone. The results indicated that these ortho-naphthoquinones could serve as promising leads for further optimization as novel substrates for NQO1.