Long-term clinical benefit of Peg-IFNα and NAs sequential anti-viral therapy on HBV related HCC.

Analysis of the value of long-term antiviral therapy using sequential Peg-IFN therapy and nucleos(t)ide analogues (NAs) improves the prognosis of HBV-related HCC. HBV-related HCC patients were classified into sequential therapy with Peg-IFNα-2a and NAs, and NAs therapy alone. All patients were followed up for 5 years. The survival rate, HCC recurrence rate, Child-Pugh score, and side effects of drugs were evaluated. Firstly, the early and late cumulative survival rate was higher in patients receiving antiviral therapy compared with the control patients (p<0.05). Patients receiving sequential therapy with Peg-IFNα-2a and NAs showed a higher late cumulative survival rate and significantly reduced early and late recurrence rate, compared to those in the NA-alone group (p<0.05). Single NAs therapy only reduced the late recurrence rate in HCC-patients. Secondly, NAs therapy significantly increased the Child-Pugh score after five years of therapy (five-year therapy 7.03±1.50 vs. initial score 6.63±0.85; p<0.05), whereas the sequential therapy with Peg-IFNα-2a and NAs did not greatly alter the Child-Pugh score (6.88±1.26; p>0.05). Compared to the control patients, patients receiving antiviral therapy (NAs alone or sequential therapy with Peg-IFNα-2a and NAs) exhibited a significantly decreased Child-Pugh score (p<0.05). Compared to NAs alone, sequential therapy with Peg-IFNα-2a and NAs provided a more efficient strategy for improving both the five-year survival rate and the two-year or five-year recurrence rate in patients.

A Jurassic mammaliaform and the earliest mammalian evolutionary adaptations.

The earliest evolution of mammals and origins of mammalian features can be traced to the mammaliaforms of the Triassic and Jurassic periods that are extinct relatives to living mammals. Here we describe a new fossil from the Middle Jurassic that has a mandibular middle ear, a gradational transition of thoracolumbar vertebrae and primitive ankle features, but highly derived molars with a high crown and multiple roots that are partially fused. The upper molars have longitudinal cusp rows that occlude alternately with those of the lower molars. This specialization for masticating plants indicates that herbivory evolved among mammaliaforms, before the rise of crown mammals. The new species shares the distinctive dental features of the eleutherodontid clade, previously represented only by isolated teeth despite its extensive geographic distribution during the Jurassic. This eleutherodontid was terrestrial and had ambulatory gaits, analogous to extant terrestrial mammals such as armadillos or rock hyrax. Its fur corroborates that mammalian integument had originated well before the common ancestor of living mammals.

Development and characterization of octreotide-modified curcumin plus docetaxel micelles for potential treatment of non-small-cell lung cancer.

We prepared octreotide (OCT)-modified curcumin plus docetaxel micelles to enhance active targeting and inhibit tumor metastasis by destroying vasculogenic mimicry (VM) channels. Soluplus was applied as an amphiphilic material to form micelles via film dispersion. The cytotoxic effects, active cellular targeting, and inhibitory effects on metastasis were systematically evaluated in vitro using A549 cells, and in vivo antitumor effects were evaluated using xenograft tumor-bearing mice. In vitro assays indicated that the OCT-modified curcumin plus docetaxel micelles showed robust cytotoxicity on A549 cells and effectively inhibited VM channels and tumor metastasis. Studying the mechanism of action indicated that OCT-modified curcumin plus docetaxel micelles downregulated MMP-2 and HIF-1α. In vivo assays indicated that OCT-modified curcumin plus docetaxel micelles increased drug accumulation at tumor sites and showed obvious antitumor efficacy. The developed OCT-modified curcumin plus docetaxel micelles may offer a promising treatment strategy for non-small-cell lung cancer.

YKL071W from Saccharomyces cerevisiae encodes a novel aldehyde reductase for detoxification of glycolaldehyde and furfural derived from lignocellulose.

Aldehydes generated as by-products during the pretreatment of lignocellulose are the key inhibitors to Saccharomyces cerevisiae, which is considered as the most promising microorganism for industrial production of biofuel, xylitol as well as other special chemicals from lignocellulose. S. cerevisiae has the inherent ability to in situ detoxify aldehydes to corresponding alcohols by multiple aldehyde reductases. Herein, we report that an uncharacterized open reading frame YKL071W from S. cerevisiae encodes a novel "classical" short-chain dehydrogenase/reductase (SDR) protein with NADH-dependent enzymatic activities for reduction of furfural (FF), glycolaldehyde (GA), formaldehyde (FA), and benzaldehyde (BZA). This enzyme showed much better specific activities for reduction of GA and FF than FA and BZA, and displayed much higher Km and Kcat/Km but lower Vmax and Kcat for reduction of GA than FF. For this enzyme, the optimum pH was 5.5 and 6.0 for reduction of GA and FF, and the optimum temperature was 30 °C for reduction of GA and FF. Both pH and temperature affected stability of this enzyme in a similar trend for reduction of GA and FF. Cu2+, Zn2+, Ni2+, and Fe3+ had severe inhibition effects on enzyme activities of Ykl071wp for reduction of GA and FF. Transcription of YKL071W in S. cerevisiae was significantly upregulated under GA and FF stress conditions, and its transcription is most probably regulated by transcription factor genes of YAP1, CAD1, PDR3, and STB5. This research provides guidelines to identify more uncharacterized genes with reductase activities for detoxification of aldehydes derived from lignocellulose in S. cerevisiae.

Leaching kinetics and bioaccumulation potential of additive-derived organophosphate esters in microplastics.

Considerable research has been conducted to evaluate microplastics (MPs) as vehicles for the transfer of hazardous pollutants in organisms. However, little effort has been devoted to the chemical release of hazardous additive-derived pollutants from MPs in gut simulations. This study looked at the leaching kinetics of organophosphate esters (OPFRs) from polypropylene (PP) and polystyrene (PS) MPs in the presence of gut surfactants, specifically sodium taurocholate, at two biologically relevant temperatures for marine organisms. Diffusion coefficients of OPFRs ranged from 1.71 × 10-20 to 4.04 × 10-18 m2 s-1 in PP and 2.91 × 10-18 to 1.51 × 10-15 m2 s-1 in PS. The accumulation factors for OPFRs in biota-plastic and biota-sediment interactions ranged from 1.52 × 10-3-69.1 and 0.02-0.7, respectively. Based on B3LYP/6-31G (d,p) calculations, the biodynamic model analysis revealed a slight increase in the bioaccumulation of OPFRs at a minor dose of 0.05% MPs. However, at higher concentrations (0.5% and 5% MPs), there was a decrease in bioaccumulation compared to the lower concentration for most OPFR compounds. In general, the ingestion of PE MPs notably contributed to the bioaccumulation of OPFRs in lugworms, whereas the contribution of PP and PS MPs was minimal. This could vary among sites exhibiting varying levels of MP concentrations or MPs displaying stronger affinities towards chemicals.

Bryum billardieri Schwaegr. against EV71 infection: in vitro and in vivo antiviral effects, identification of molecular mechanisms and active monomers.

Enterovirus 71 (EV71) commonly causes symptoms such as hand, foot, and mouth disease (HFMD) in infants and children and may lead to neurological disease and even death in severe cases. Appropriate vaccines for the prevention of HFMD are available in the clinic; however, they present different and serious adverse effects that cannot guarantee compliance and efficacy. The purpose of this study was to analyze the potential mechanism of Bryum billardieri Schwaegr. (BBS) against EV71 and analyze its potential active components. A previous in vitro antiviral assay was used to determine the best extraction method for the active site of BBS against EV71, and the results showed that the antiviral activity of BBS was more pronounced in the fraction that was extracted by aqueous extraction and alcoholic precipitation and then obtained by purification on a silica gel column (dichloromethane:methanol = 0:100). In addition, the therapeutic effects of BBS on EV71-infected mice were further investigated by in vivo pharmacological experiments. BBS reduced the lung index, viral titer, and degree of EV71-induced lung, brain, and skeletal muscle damage. The mechanism of anti-EV71 activity of BBS was also investigated by using ELISA and qRT-PCR, and it was found that BBS exerted its action mainly by regulating the expression of TLR3, TLR4, TNF-α, IL-2, and IFN-γ by modulating the activation of NF-κB and JAK2/STAT1 signaling pathways. Finally, the chemical structures of the active monomers in BBS were determined by using UPLC-MS and NMR techniques. The study revealed that one of the monomers on which BBS exerts its antiviral activity is saponarin. In conclusion, the results of this study suggest that BBS is considered a natural anti-EV71 product with enormous potential, and saponarin would be its non-negligible active monomer.

A detailed comparison of two species in the genus Potamanthus Pictet, 1843 from China (Ephemeroptera, Potamanthidae).

Photographs and details of structures of two Potamanthus species, P.huoshanensis Wu, 1987 and P.luteus (Linnaeus, 1767), are presented for the first time. Here, based upon Chinese specimens of those species, all external structures are illustrated digitally and compared. The results and photos clearly show that the adults of the two species are different in wing color and genitalia shape, and that their nymphs have different mandibular tusks and forelegs. Specifically, P.luteus has a more colorful body and wings, longer penes and nymphal mandibular tusks but shorter foretarsi than those of P.huoshanensis. This comparison not only confirms the differences between these two similar species, but also supports the updated generic delineations of Potamanthus and Potamanthodes.

Systematics of Potamanthodes nanchangi Hsu, 1936 (Ephemeroptera: Potamanthidae).

The enigmatic mayfly Potamanthodes nanchangi Hsu, 1936 was briefly described based on a male. Currently, this species has an unclear taxonomic position and no supporting type specimen, consequently its recognition, differentiation and classification is vague. In this study, by using fresh specimens from type locality in Jiangxi province at central China, this species is redescribed, photographed, and a neotype is designated. This species evidently belongs to the genus Potamanthodes Ulmer, 1920 by its short mandibular tusks (shorter than head), presence of setae row on forefemora of nymphs, slender and deeply bifurcated V-shaped penes, common base of MP2 and CuA of forewings. Significant morphological characters defining this species are relatively long penial tips, greatly bent R1 of hindwings and small compound eyes of the males, large mandibular tusks and long forelegs of the nymphs. Therefore, the P. nanchangi is indeed a valid and apomorphic species in the genus Potamanthodes.

Scalable Formation of Highly Viable and Functional Hepatocellular Carcinoma Spheroids in an Oxygen-Permeable Microwell Device for Anti-Tumor Drug Evaluation.

For high-throughput anti-cancer drug screening, microwell arrays may serve as an effective tool to generate uniform and scalable tumor spheroids. However, microwell arrays are commonly anchored in non-oxygen-permeable culture plates, leading to limited oxygen supply for avascular spheroids. Herein, a polydimethylsiloxane (PDMS)-based oxygen-permeable microwell device is introduced for generating highly viable and functional hepatocellular carcinoma (HCC) spheroids. The PDMS sheets at the bottom of the microwell device provide a high flux of oxygen like in vivo neighboring hepatic sinusoids. Owing to the better oxygen supply, the generated HepG2 spheroids are larger in size and exhibit higher viability and proliferation with less cell apoptosis and necrosis. These spheroids also exhibit lower levels of anaerobic cellular respiration and express higher levels of liver-related functions. In anti-cancer drug testing, spheroids cultured in PDMS plates show a significantly stronger resistance against doxorubicin because of the stronger stem-cell and multidrug resistance phenotype. Moreover, higher expression of vascular endothelial growth factor-A produces a stronger angiogenesis capability of the spheroids. Overall, compared to the spheroids cultured in conventional non-oxygen-permeable plates, these spheroids can be used as a more favorable model for early-stage HCCs and be applied in high-throughput anti-cancer drug screening.

The genus Rhoenanthus Eaton, 1881 in China with the redescription of R. hunanensis You amp; Gui, 1995 (Ephemeroptera: Potamanthidae).

The potamanthid mayfly genus Rhoenanthus Eaton, which was not investigated systematically before in China, is revised herein. Six species in the subgenus Potamanthindus are recognized. Among them, R. sapa, R. obscurus and R. coreanus are new records for this country, and the presence in China of the species R. magnificus and R. hunanensis is confirmed, the nymphal stage of the latter species being described for the first time. Phylogenetically and evolutionarily, R. sapa, which has shorter maxillary and labial palpi, foretibiae and less setaceous mouthparts and forelegs, is close to the plesiomorphic genus Potamanthus. At the same time, R. youi, R. obscurus and R. coreanus, which have larger tusks and spines, longer and more setaceous foretibiae, maxillary and labial palpi, are somewhat similar to the other subgenus Rhoenanthus (Rhoenanthus). The Chinese Rhoenanthus (Potamanthindus) species indicate that the genus Rhoenanthus is closer to Anthopotamus rather than Potamanthus, both of them bearing elongated mandibular tusks.

Two new species of the genus Notacanthurus from China (Ephemeroptera: Heptageniidae, Ecdyonurinae).

Previously, only three of seven species in the Asian genus Notacanthurus were reported both nymphs and imagoes, and no Chinese species was found. Here two new species collected from China, which are named as Notacanthurus maculatus sp. n. and N. lamellosus sp. n. respectively, are described and pictured in detail. The nymph of N. maculatus sp. n. has following combined characters: posterior margin of sternum IX straight, claws with two subapical denticles, and gills V-VI with arrow-like accessory lobes. The male imago has unspecialized anterior margin of head and Electrogena-like penis lobes. The second species N. lamellosus sp. n. is more distinguishable. Its nymph has pale dots on head, median dorsal ridges on abdominal terga I-IX, claws with five subapical denticles, and dorsal lamellae of gills II-IV divided into two portions. Anterior margin of male imago is not protruding either, forewings have less pigmented crossveins between Sc and R1, and penis lobes have apical and ventral sclerites. A key to all known nymphs of the genus is provided.

New Jurassic mammaliaform sheds light on early evolution of mammal-like hyoid bones.

We report a new Jurassic docodontan mammaliaform found in China that is preserved with the hyoid bones. Its basihyal, ceratohyal, epihyal, and thyrohyal bones have mobile joints and are arranged in a saddle-shaped configuration, as in the mobile linkage of the hyoid apparatus of extant mammals. These are fundamentally different from the simple hyoid rods of nonmammaliaform cynodonts, which were likely associated with a wide, nonmuscularized throat, as seen in extant reptiles. The hyoid apparatus provides a framework for the larynx and for the constricted, muscularized esophagus, crucial for transport and powered swallowing of the masticated food and liquid in extant mammals. These derived structural components of hyoids evolved among early diverging mammaliaforms, before the disconnection of the middle ear from the mandible in crown mammals.

[The study on the enamel remineralization by enamel matrix proteins' inducing].

OBJECTIVE: To find the enamel matrix proteins on the impact of enamel mineralization through experiments. METHODS: A combination of protein and beneficial carboxyl groups was grafted on the surface of enamel defects of rats through UV radiation then put into the enamel matrix proteins of calcium phosphate agar acetate solution systems, through scanning enamel surface with the electron microscopy to observe the morphological changes of enamel then analyse the regulation that enamel matrix proteins have done to the white hydroxyapatite crystals on the composition and morphology. RESULTS: In the enamel matrix protein added gel system, we can see the growth of hydroxyapatite crystals, and crystal showed a good degree of crystallinity and contained a small amount of CO3(2-) substituted hydroxyapatite crystals. CONCLUSION: The temperature at 37 degrees C water bath, after adding the enamel matrix proteins to gel system, the new hydroxyapatite crystals were numerous which proved that enamel matrix proteins played an important role in nucleation and growth of hydroxyapatite crystal, so it could be indicated that enamel matrix proteins could induce the enamel remineralization.

Cranial morphology of Sinovenator changii (Theropoda: Troodontidae) on the new material from the Yixian Formation of western Liaoning, China.

A new three-dimensionally preserved troodontid specimen consisting of most of the skull, partial mandibles and six articulated cervical vertebrae (PMOL-AD00102) from the Early Cretaceous Yixian Formation of Beipiao, western Liaoning, China is identified as Sinovenator changii on the basis of a surangular with a "T"-shaped cross-section. High-resolution computed tomographic data for the skull of this new specimen facilitated a detailed description of the cranial anatomy of S. changii. New diagnostic features of S. changii include a well-developed medial shelf on the jugal, a slender bar in the parasphenoid recess, a lateral groove on the pterygoid flange of the ectopterygoid, and the lateral surface of the anterior cervical vertebrae bearing two pneumatic foramina. Our new observation confirms that the braincase of Sinovenator is not as primitive as previously suggested, although it still shows an intermediate state between derived troodontids and non-troodontid paravians in having an initial stage of the subotic recess and the otosphenoidal crest. Additionally, this new specimen reveals some novel and valuable anatomical information of troodontids regarding the quadrate-quadratojugal articulation, the stapes, the epipterygoid and the atlantal ribs.

Regulatory polymorphism of CXCL10 rs1439490 in seronegative occult hepatitis C virus infection.

AIM: To examine the relationship between the single nucleotide polymorphism CXCL10 rs1439490 and seronegative occult hepatitis C virus (HCV) infection (OCI). METHODS: One hundred and three cases of seronegative OCI and 155 cases of seropositive chronic HCV infection (CHC) were diagnosed at five Liver Centers in Northeastern China, from 2012 to 2016. CXCL10 rs1439490, rs1440802, and IL-28B rs12979860 were analyzed by sequencing. Serum CXCL10 was measured by ELISA. Intrahepatic CXCL10 was determined by quantitative PCR and immunohistochemical semi-quantitative scoring. Liver necroinflammation and fibrosis were scored according to the METAVIR system. RESULTS: CXCL10 rs1439490 G/G was more prevalent in OCI patients (n = 93/103; 90.3%) than in CHC patients (n = 116/155; 74.8%; P = 0.008). OCI patients had lower serum CXCL10 levels than CHC patients (192.91 ± 46.50 pg/mL vs 354.78 ± 102.91 pg/mL, P < 0.0001). Of IL-28B rs12979860 C/C patients, OCI patients with rs1439490 G/G had lower serum and liver levels of CXCL10 and lower levels of liver necroinflammation and fibrosis than non-G/G patients. OCI patients had higher alanine aminotransferase normalization rates after Peg-interferon treatment than CHC patients (P < 0.05) and serum CXCL10 decreased significantly (P < 0.0001). Liver necroinflammation and fibrosis were alleviated in 8 OCI patients after treatment. Multivariate analysis indicated that rs1439490 G/G significantly influenced the occurrence of OCI in HCV infection (OR = 0.31, 95%CI: 0.15-0.66, P = 0.002). CONCLUSION: CXCL10 rs1439490 G/G is positively associated with OCI in HCV infection and antiviral outcome.

The toothless pterosaur Jidapterus edentus (Pterodactyloidea: Azhdarchoidea) from the Early Cretaceous Jehol Biota and its paleoecological implications.

BACKGROUND: In the Early Cretaceous Jehol Biota, the toothless pterosaurs flourished with the chaoyangopterids and tapejarids playing a key role in understanding the early diversity and evolution of the Azhdarchoidea. Unlike the more diverse tapejarids, the rarer chaoyangopterids are characterized by a long and low rostrum, supporting a close relationship with the huge azhdarchids. Unfortunately, our knowledge is still limited in the osteology, paleoecology, and taxonomy of the Chaoyangopteridae. As one of the best preserved skeletons, the type and only specimen of Jidapterus edentus provides an opportunity to understand the morphology and paleoecology of the chaoyangopterids. RESULTS: Our study of the osteology of Jidapterus edentus reveals valuable information about the morphology of the Chaoyangopteridae such as a rostrum with a curved dorsal profile, high Rostral Index (RI), larger angle between the dorsal and postorbital processes of the jugal, sequentially shorter fourth to seventh cervical vertebrae, sternum with a plate wider than long, contact of the metacarpal I with the distal syncarpal, pneumatic foramen on first wing phalanx, hatchet-like postacetabular process with unconstricted neck and small dorsal process, distinctly concave anterior margin of pubis, subrectangular pubic plate with nearly parallel anterior and posterior margins, longer proximal phalanges of pedal digits III and IV, as well as reduced and less curved pedal unguals. These features further support the validity of Jidapterus edentus as a distinct species and the close relationship of the chaoyangopterids with the azhdarchids. Paleoecologically, the chaoyangopterids are probably like the azhdarchids, more terrestrial than the contemporaneous and putatively arboreal tapejarids, which may have been limited to the forest-dominated ecosystem of the Jehol Biota. DISCUSSION: The osteology of Jidapterus edentus further supports the close relationship of the Chaoyangopteridae with the Azhdarchidae in sharing a high RI value and reduced and mildly-curved pedal unguals, and it also implies a possible paleoecological similarity in their terrestrial capability. Combined with the putatively arboreal and herbivorous tapejarids, this distinct lifestyle of the chaoyangopterids provides new insights into the diversity of pterosaurs in the ecosystem of the Jehol Biota.

Earliest filter-feeding pterosaur from the Jurassic of China and ecological evolution of Pterodactyloidea.

Pterosaurs were a unique clade of flying reptiles that were contemporaries of dinosaurs in Mesozoic ecosystems. The Pterodactyloidea as the most species-diverse group of pterosaurs dominated the sky during Cretaceous time, but earlier phases of their evolution remain poorly known. Here, we describe a 160 Ma filter-feeding pterosaur from western Liaoning, China, representing the geologically oldest record of the Ctenochasmatidae, a group of exclusive filter feeders characterized by an elongated snout and numerous fine teeth. The new pterosaur took the lead of a major ecological transition in pterosaur evolution from fish-catching to filter-feeding adaptation, prior to the Tithonian (145-152 Ma) diversification of the Ctenochasmatidae. Our research shows that the rise of ctenochasmatid pterosaurs was followed by the burst of eco-morphological divergence of other pterodactyloid clades, which involved a wide range of feeding adaptations that considerably altered the terrestrial ecosystems of the Cretaceous world.

A new species of the genus Teloganopsis with setaceous mouthparts and forelegs from southern China (Ephemeroptera, Ephemerellidae).

The nymph and reared male and female of a new ephemerellid species, which was collected from southern China and named Teloganopsis setosa Zhou, sp. n., are described. The nymph is unique because of its long and dense setae on labrum, mandibles, maxillae, labium, and forelegs as well as the elongated segments II of labial palpi and expanded paraglossae. The male can be differentiated from close relatives by its larger penis lobes with dorsolateral projections, and the more pigmented tergum IV and caudal filaments. The nymph described in this paper represents a new adaptive and ecological type in the family Ephemerellidae.

Preparation and biocompatibility of tissue-engineered scaffold materials based on collagen.

OBJECTIVE: To prepare a tissue-engineered scaffold material using collagen as the matrices and to study the blood compatibility and tissue biocompatibility of this material. METHODS: Physical, chemical and physical/chemical methods were used for the crosslinking of the collagen. RESULTS: Dynamic blood clotting tests indicated that the blood clotting index (BCI) of the crosslinked collagen materials prepared by different means decreased as their contact with the blood was prolonged, and the collagen material obtained after crosslink through 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide method showed the highest BCI after contact with the blood within certain length of time. Hemolysis ratios of all the crosslinked collagen materials were shown to be much lower than 5%, well conforming to the requirement of biomaterials. Scanning electron microscopy showed that the platelets attached to the surface of the crosslinked collagen materials, having a fairly small number, were not morphologically distorted. CONCLUSION: The collagen materials obtained by the 3 crosslink methods have good blood compatibility. The cells grow well on the surfaces of the materials, indicating their good biocompatibility.