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ABSTRACT The field of conservation genomics is becoming increasingly interested in whether, and how, structural variant (SV) genotype information can be leveraged in the management of threatened species. The functional consequences of SVs are more complex than for single nucleotide polymorphisms (SNPs), as SVs typically impact a larger proportion of the genome due to their size and thus may be more likely to contribute to load. While the impacts of SV‐specific genetic load may be less consequential for large populations, the interplay between weakened selection and stochastic processes means that smaller populations, such as those of the threatened Aotearoa hihi/New Zealand stitchbird (Notiomystis cincta), may harbour a high SV load. Hihi were once confined to a single remnant population, but have been reestablished into six sanctuaries and reserves, often via secondary bottlenecks, resulting in low genetic diversity, low adaptive potential, and inbreeding depression. In this study, we use whole genome resequencing of 30 individuals from the Tiritiri Matangi population to identify the nature and distribution of both SNPs and SVs within this small avian population. We find that SNP and SV individual mutation load is only moderately correlated, likely because SVs arise in regions of high recombination and that are less evolutionarily conserved. Finally, we leverage a long‐term monitoring dataset of pedigree and fitness data to assess the impact of SNP and SV mutation loads on individual fitness, and find that SNP and SV realised load had similar negative correlations with lifetime fitness. However, of the masked load metrics, only SVs had a positive significant correlation with lifetime fitness, indicating that masking of deleterious alleles may be more important for SVs than for SNPs. The results of this study indicate that only examining SNPs neglects important aspects of intra‐specific variation and that studying SVs has direct implications for linking genetic diversity and genomic health to inform management decisions. [ABSTRACT FROM AUTHOR]

Objective: Expand genetic screening for atypical Type I sialidosis (ST‐1) could address its underdiagnosed in both progressive myoclonic ataxia (PMA) and ataxia patients. To evaluate the potential founder effect of mutation in the population. Methods: We enrolled 231 patients with PMA or ataxia from the First Affiliated Hospital of Fujian Medical University. Through Whole Exome Sequencing and Sanger sequencing, we identified the causative gene in patients. Haplotype analysis was employed to explore a potential founder effect of the NEU1 c.544A>G mutation. Results: A total of 31 patients from 23 unrelated families were genetically diagnosed with ST‐1. A significant 80.6% of these patients were homozygous for the c.544A>G mutation. We discovered six different NEU1 variants, including two novel mutations: c.951_968del and c.517T>G. The mean age of onset was 18.0 ± 7.1 years. The clinical spectrum of ST‐1 featured ataxia and myoclonus as the most common initial symptoms. Over 40% suffered from controlled generalized tonic–clonic seizures. Mobility and independence varied greatly across the cohort. Cherry‐red spots were rare, occurring in just 9.5% (2/21) of patients. Brain MRIs were typically unremarkable, except for two patients with unusual findings. EEGs showed diffuse paroxysmal activity in 17 patients. The c.544A>G mutation in NEU1 is a founder variant in Fujian, with a unique haplotype prevalent in East Asians. Interpretation: ST‐1 should be suspected in patients with PMA or ataxia in Southeast China, even without macular cherry‐red spots and seizures, and the premier test could be a variant screening of the founder variant NEU1 c.544A>G. [ABSTRACT FROM AUTHOR]

In developed cities, bird communities are typically comprised of a few dominant invasive species that can cause considerable social and economic costs. While various studies advocate restricting anthropogenic food as a suitable management approach, a significant knowledge gap persists regarding how these species interact and respond to such an intervention. Here, we evaluate whether limiting a shared food resource may affect their abundances similarly and assess whether such limitations influence their niche dynamics.In Singapore, open food centres for people, colloquially known as hawker centres, serve as key food sources for three highly adapted urban birds: feral pigeons, Javan mynas and house crows. We counted these three species across 63 hawker centres and analysed their niche dynamics across different phases—before, during COVID‐19 social restrictions when dining‐in was prohibited, and during an enforcement phase mandating the return of crockery. We modelled their counts, diet niche widths and niche overlaps, considering predictors which include the sampling phases, food availability, structural characteristics of hawker centres and spatial attributes such as distance to public housing.During social restrictions, feral pigeon and Javan myna counts showed a significant decline, while the count proportions of the three species compared to each other remained relatively stable. Hawker centres closer to bridges and public housing, and those that structurally more open, attracted more birds.The niche widths of feral pigeons and Javan mynas significantly narrowed during social restrictions due to reduced food availability. However, their niche overlaps remained consistent across sampling phases, indicating resource partitioning strategies to cope with extreme food shortages—feral pigeons adapted by foraging more on grass verges outside, while Javan mynas frequented tray return stations. This resilience in maintaining species proportions and the absence of significant niche overlap suggested the existence of an ecological balance despite substantial reductions in available food.Synthesis and applications. Our study underscores the importance of controlling human‐provided food to collectively manage dominant urban bird commensals. Beyond the two social restriction phases, curbing the availability of anthropogenic food through enforcement also kept nuisance birds away, validating a cost‐effective approach in reducing their counts. [ABSTRACT FROM AUTHOR]

The porcine epidemic diarrhea virus (PEDV) has caused severe economic losses in the pig industry. Since its discovery, the virus has spread in pig herds for more than 50 years. Many new features have been found in the PEDV spike genes. In this study, 123 representative S genes were used to analyze their characteristics across strains. Phylogenetic analysis revealed that PEDV can be divided into nine groups: G1a, G1b, G1c, G1d, G2a, G2b, G2c, G2d, and G3. In addition, 21 different lengths of the S gene were found. Analysis of the amino acid insertion and deletion sites revealed that most deletions and insertions occurred in the loops of the spike quaternary structure, primarily in the D0 and N‐terminal domains (NTDs). According to the above results, PEDV has undergone considerable evolution, possibly under the immune pressure of vaccination. These results are highly important for understanding the current epidemic situation of PEDV. [ABSTRACT FROM AUTHOR]

BACKGROUND: Cry1Ab has emerged as a bio‐insecticide to control Spodoptera litura (Lepidoptera: Noctuidae). However, the sublethal effects of Cry1Ab on the physiological changes and molecular level of S. litura have not been well documented. Our aims in this study were to assess the sublethal effect of Cry1Ab on S. litura, including midgut and Malpighian tubules as targets. RESULTS: After sublethal Cry1Ab exposure, distinct histological alterations were mainly observed in the midgut. Furthermore, the results of comparative RNA sequencing and tandem mass tag‐based proteomics showed that, in the midgut, most differential expression genes (DEGs) were up‐regulated and significantly enriched in the serine protease activity pathway, and up‐regulated differential expression proteins (DEPs) were mainly associated with the oxidative phosphorylation pathway, whereas the down‐regulated involved in the ribosome pathways. In the Malpighian tubules, DEGs and DEPs were significantly enriched in the ribosome pathway. We proposed that ribosome may act as a universal target in energy metabolism with other pathways via the results of protein–protein interaction analysis. Further, by verification of the mRNA expression of some Cry protein receptor and detoxification genes after Cry1Ab treatment, it was suggested that the ribosomal proteins (RPs) possibly participate in influencing the Bt‐resistance of S. litura larvae under sublethal Cry1Ab exposure. CONCLUSION: Under sublethal Cry1Ab exposure, the midgut of S. litura was damaged, and the proteotranscriptomic analysis elucidated that Cry1Ab disrupted the energy homeostasis of larvae. Furthermore, we emphasized the potential role of ribosomes in sublethal Cry1Ab exposure. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Plitidepsin (or dehydrodidemnin B), an approved anticancer drug, belongs to the didemnin family of cyclic depsipeptides, which are found in limited quantities in marine tunicate extracts. Herein, we introduce a new approach that integrates microbial and chemical synthesis to generate plitidepsin and its analogues. We screened a Tistrella strain library to identify a potent didemnin B producer, and then introduced a second copy of the didemnin biosynthetic gene cluster into its genome, resulting in a didemnin B titer of approximately 75 mg/L. Next, we developed two straightforward chemical strategies to convert didemnin B into plitidepsin, one of which involved a one‐step synthetic route giving over 90 % overall yield. Furthermore, we synthesized 13 new didemnin derivatives and three didemnin probes, enabling research into structure–activity relationships and interactions between didemnin and proteins. Our study highlights the synergistic potential of biosynthesis and chemical synthesis in overcoming the challenge of producing complex natural products sustainably and at scale. [ABSTRACT FROM AUTHOR]

Cerebral infarction is one of the most common diseases for aged people. Compound Tongluo Decoction (CTLD), a classic traditional Chinese Medicine prescription, has been widely used in the treatment of ischemic cerebral infarction. Transient middle cerebral artery occlusion (tMCAO) rat model is established for the animal experiment and oxygen‐glucose deprivation and reperfusion (OGD/R) human umbilical vein endothelial cells (HUVECs) model are established for the cell experiment. This also use Nrf2‐/‐ rats to detect the role of nuclear factor erythroid 2‐related factor 2 (Nrf2). Longa score, Evans blue staining, brain water content measurement, and histological observation are done. The levels of reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), and other ferroptosis‐related components are detected respectively. In the vivo experiment, CTLD relieved ischemia‐reperfusion (IR) injury symptoms and attenuated IR injury in brain tissues of tMCAO rats by relieving peroxidation injury in brain tissues and inhibiting ferroptosis in tMCAO rats. Moreover, CTLD reversed OGD/R‐induced oxidative damage of endothelial cells via suppressing ferroptosis. After knocking out the Nrf2 gene, the protective effect of CTLD is sharply reduced. This study put forward that CTLD can inhibit ferroptosis in I/R‐injured vascular endothelium by regulating Nrf2/ARE/SLC7A11 signaling to improve the relative symptoms of rats after cerebral I/R injury, thus providing a viable treatment option for cerebrovascular disease. [ABSTRACT FROM AUTHOR]

The assembly line biosynthesis of the powerful anticancer‐antiviral didemnin cyclic peptides is proposed to follow a prodrug release mechanism in Tristella bacteria. This strategy commences with the formation of N‐terminal prodrug scaffolds and culminates in their cleavage during the cellular export of the mature products. In this study, a comprehensive exploration of the genetic and biochemical aspects of the enzymes responsible for both the assembly and cleavage of the acylated peptide prodrug scaffolds is provided. This process involves the assembly of N‐acyl‐polyglutamine moieties orchestrated by the nonribosomal peptide synthetase DidA and the cleavage of these components at the post‐assembly stage by DidK, a transmembrane CAAX hydrolase homolog. The findings not only shed light on the complex prodrug mechanism that underlies the synthesis and secretion of didemnin compounds but also offer novel insights into the expanded role of CAAX hydrolases in microbes. Furthermore, this knowledge can be leveraged for the strategic design of genome mining approaches aimed at discovering new bioactive natural products that employ similar prodrug biochemical strategies. [ABSTRACT FROM AUTHOR]

Background: Major abdominal surgery is associated with a high rate of post‐operative complications with increased risk of adverse surgical outcomes due to the presence of frailty. This study aims to evaluate the effectiveness of the multimodal Recovery of Surgery in the Elderly (ROSE) prehabilitation program with supervised exercise in mitigating postoperative functional decline when compared to standard care. Method: The ROSE program enrolled ambulant patients who were 65 years and above, had a Clinical Frailty Scale score of 4 or more and were planned for major abdominal surgery. Participation in supervised exercise sessions before surgery were compared with standard physiotherapy advice. The primary outcome was 6‐min walk test (6MWT) distance assessed at baseline, after prehabilitation and 30 days follow‐up after surgery. Secondary outcomes included physical performance, length of hospital stay and postoperative morbidity. Results: Data from 74 eligible patients, 37 in each group, were included. Median age was 78 years old. Forty‐two patients (22 in Prehab group and 20 in control group) with complete 6MWT follow‐up data at 30 days follow‐up were analysed for outcomes. Most patients underwent laparoscopic surgery (63.5%) and almost all of the surgeries were for abdominal malignancies (97.3%). The Prehab group had an increase in 6MWT distance at the 30‐day follow up, from a baseline mean (SD) of 277.4 (125) m to 287.6 (143.5) m (p = 0.415). The 6MWT distance in the control group decreased from a baseline mean (SD) of 281.7 (100.5) m to 260.1 (78.6) m at the 30‐day follow up (p = 0.086). After adjusting for baseline 6MWT distance and frailty score, the Prehab group had significantly higher 6MWT distance at 30‐day follow‐up than control (difference in adjusted means 41.7 m, 95% confidence interval 8.7–74.8 m, p = 0.015). There were no significant between‐group differences in the secondary outcomes. Conclusion: A multimodal prehabilitation program with supervised exercise within a short time frame can improve preoperative functional capacity and maintain baseline functional capacity in frail older adults undergoing major abdominal surgery. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis (AD) is one of the most prevalent chronic inflammatory skin conditions. We aimed to describe the clinical features of adult‐onset and childhood‐onset AD in a multi‐ethnic Asian population. Methods: A retrospective study was performed of 188 patients with AD managed at a tertiary skin institution in Singapore. Patient demographics, clinical features and disease scores were analysed. Results: Clinical features related to pigmentary changes, such as orbital darkening and Dennie–Morgan folds were more prevalent among childhood‐onset AD patients than in adult‐onset AD patients. Similarly, features related to prolonged scratching or friction, such as anterior neck folds, perifollicular accentuation and infra‐auricular/infranasal fissuring were also more prevalent in childhood‐onset AD patients. Disease scores such as SCORAD and EASI were not different between patients with childhood versus adult‐onset disease. Conclusion: There were significant differences in clinical features between childhood‐onset and adult‐onset AD. Certain features are related to pigmentary changes and might be more accentuated in patients with skin of colour. Further studies are needed to understand how the different features might be clinically significant and related to the various AD endotypes and disease trajectories. [ABSTRACT FROM AUTHOR]

Hydrogen isotope exchange (HIE) represents one of the most attractive labeling methods to synthesize deuterium‐ and tritium‐labeled compounds. Catalytic HIE methods that enable site‐selective C−H bond activation and exchange labeling with gaseous isotopes D2 and T2 are of vital importance, in particular for high‐specific‐activity tritiation of pharmaceuticals. As part of our interest in exploring s‐block metals for catalytic transformations, we found CsN(SiMe3)2 to be an efficient catalyst for selective HIE of benzylic C−H bonds with D2 gas. The reaction proceeds through a kinetic deprotonative equilibrium that establishes an exchange pathway between C−H bonds and D2 gas. By virtue of multiple C−H bonds activation and high activity (isotope enrichment up to 99 %), the simple cesium amide catalyst provided a very powerful and practically convenient labeling protocol for synthesis of highly deuterated compounds and high‐specific‐activity tritiation of pharmaceuticals. [ABSTRACT FROM AUTHOR]

Resource partitioning may facilitate the coexistence of sympatric species with similar ecological requirements. Here, we study a colony of unusual echolocating birds called swiftlets, which nest underground on an island off the coast of Singapore. The colony comprises two congeneric swiftlet species, black‐nest swiftlets (Aerodramus maximus) and edible‐nest swiftlets (A. fuciphagus), nesting at high densities and in close proximity. Bioacoustic recordings and monitoring of nesting biology at the site across multiple seasons revealed significant differences in echolocation calls as well as survival rates between the species, with the larger black‐nest swiftlet nesting at locations with the highest fledging rates. We also observe an additional off‐season breeding peak by the smaller species, the edible‐nest swiftlet. Unexpectedly, off‐season egg‐hatching rates were significantly higher compared with the rates during the shared breeding season (mean difference = 14%). Our study on the breeding biology of these echolocating cave‐dwelling birds provides an example of spatial and temporal strategies that animals employ to partition resources within a confined habitat. [ABSTRACT FROM AUTHOR]

Summary: A new gelatin‐protocatechuic acid (PCA) film with Escherichia coli O157:H7 phage JN01 was developed and characterised. After incorporated with JN01, swelling value, water vapour permeability, water solubility and elongation at break of gelatin‐PCA film were not significantly different. The addition of JN01 increased b value and transparency of film, while it decreased L value, a value and tensile strength of film. Moreover, the gelatin‐PCA‐JN01 film presented antioxidant activity of 60.07%. Furthermore, JN01 could be steadily released from gelatin‐JN01 and gelatin‐PCA‐JN01 films in aqueous solution, and their release rates were 7.56% and 0.12% after 11 h, respectively. The microstructure analysis showed that JN01 particles were clustered and uniformly distributed in film, and the aggregation would be attenuated in the presence of PCA. Meanwhile, E. coli O157:H7 counts were 1.13 log10CFU mL−1 and 0.45 log10CFU mL−1 lower in gelatin‐JN01 and gelatin‐PCA‐JN01 films compared with pure gelatin film in vitro at 4 °C for 24 h, respectively. After stored at 4 °C for 7 days, Escherichia coli O157:H7 counts were 1.00 log10CFU g−1 and 0.80 log10CFU g−1 lower in beef packed with these two gelatin films, compared with beef without gelatin film, respectively. In conclusion, the developed gelatin‐PCA‐JN01 film has potential application in food preservation. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers, and the patients are generally diagnosed with distant metastasis. Liver is one of the preferred organs of distant metastasis, and liver metastasis is the leading cause of death in PDAC. Diet-induced obesity (DIO) is a risk factor for PDAC, and it remains unclear whether and how DIO contributes to liver metastasis of PDAC. In our study, we found that DIO significantly promoted PDAC liver metastasis compared with normal diet (ND) in intrasplenic injection mouse model. RNA-seq analysis for liver metastasis nodules showed that the various chemokines and several chemokine receptors were altered between ND and DIO samples. The expression levels of CX3CL1 and CX3CR1 were significantly upregulated in DIO-induced liver metastasis of PDAC compared to ND. Increased CX3CL1 promoted the recruitment of CX3CR1-expressing pancreatic tumor cells. Taken together, our data demonstrated that DIO promoted PDAC liver metastasis via CX3CL1/CX3CR1 axis. [ABSTRACT FROM AUTHOR]

2D heterostructures have garnered tremendous attention for potential applications in electronics and optoelectronics. Heterostructures can be constructed by assembling individual atomically thin layers of 2D materials into integrated devices, which involves three primary degrees of freedom (DOFs), i.e., Lego‐like basic building blocks, out‐of‐plane stacking order, and in‐plane twist‐angle alignment. By steering the DOFs of 2D materials, devices and structures such as artificial Shockley junction, quantum wells, and superlattices can be conveniently established based on well‐developed fabrication and/or assembly techniques, beneficial for next‐generation ultracompact information technologies. Herein, the recent progress on constructing the artificial atomic structures by taking advantage of three primary DOFs is overviewed. An outlook of the challenges and future developments is presented as well. Future advancements in the rational construction of complex devices and artificial heterostructures are also suggested. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to analyze the characteristics of the COVID‐19 publications in the ten psychology‐related Web of Science categories in the social science citation index 10‐month following the COVID‐19 outbreak. Methods: Six publication indicators were examined across authors, institutions, and countries. Results: Analyses showed that the United States has produced the highest number of empirical investigations into the psychological impact of COVID‐19, and the majority of the research across all countries was in clinical and psychopathology. Distribution of journals and psychology‐related Web of Science categories were analyzed. Frequently used words in article title, author keywords, and KeyWords Plus were also presented. Conclusions: The findings suggest that there are substantial clinical implications associated with COVID‐19. There are recommendations offered for future research and clinical practice. [ABSTRACT FROM AUTHOR]

Objectives: The origin and differentiation of Austronesian populations and their languages have long fascinated linguists, archeologists, and geneticists. However, the founding process of Austronesians and when they separated from their close relatives, such as the Daic and Austro‐Asiatic populations in the mainland of Asia, remain unclear. In this study, we explored the paternal origin of Malays in Southeast Asia and the early differentiation of Austronesians. Materials and Methods: We generated whole Y‐chromosome sequences of 50 Malays and co‐analyzed 200 sequences from other Austronesians and related populations. We generated a revised phylogenetic tree with time estimation. Results: We identified six founding paternal lineages among the studied Malays samples. These founding lineages showed a surprisingly coincident expansion age at 5000 to 6000 years ago. We also found numerous mostly close related samples of the founding lineages of Malays among populations from Mainland of Asia. Conclusion: Our analyses provided a refined phylogenetic resolution for the dominant paternal lineages of Austronesians found by previous studies. We suggested that the co‐expansion of numerous founding paternal lineages corresponds to the initial differentiation of the most recent common ancestor of modern Austronesians. The splitting time and divergence pattern in perspective of paternal Y‐chromosome evidence are highly consistent with the previous theories of ethnologists, linguists, and archeologists. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this research was to explore the origin, diversification, and demographic history of O1a‐M119 over the past 10,000 years, as well as its role during the formation of East Asian and Southeast Asian populations, particularly the Han, Tai‐Kadai‐speaking, and Austronesian‐speaking populations. Materials and Methods: Y‐chromosome sequences (n = 141) of the O1a‐M119 lineage, including 17 newly generated in this study, were used to reconstruct a revised phylogenetic tree with age estimates, and identify sub‐lineages. The geographic distribution of 12 O1a‐M119 sub‐lineages was summarized, based on 7325 O1a‐M119 individuals identified among 60,009 Chinese males. Results: A revised phylogenetic tree, age estimation, and distribution maps indicated continuous expansion of haplogroup O1a‐M119 over the past 10,000 years, and differences in demographic history across geographic regions. We propose several sub‐lineages of O1a‐M119 as founding paternal lineages of Han, Tai‐Kadai‐speaking, and Austronesian‐speaking populations. The sharing of several young O1a‐M119 sub‐lineages with expansion times less than 6000 years between these three population groups supports a partial common ancestry for them in the Neolithic Age; however, the paternal genetic divergence pattern is much more complex than previous hypotheses based on ethnology, archeology, and linguistics. Discussion Our analyses contribute to a better understanding of the demographic history of O1a‐M119 sub‐lineages over the past 10,000 years during the emergence of Han, Austronesians, Tai‐Kadai‐speaking populations. The data described in this study will assist in understanding of the history of Han, Tai‐Kadai‐speaking, and Austronesian‐speaking populations from ethnology, archeology, and linguistic perspectives in the future. [ABSTRACT FROM AUTHOR]

Objectives: Haplogroup C2a‐M48 is the predominant paternal lineage of Tungusic‐speaking populations, one of the largest population groups in Siberia. Up until now, the origins and dispersal of Tungusic‐speaking populations have remained unclear. In this study, the demographic history of Tungusic‐speaking populations was explored using the phylogenetic analysis of haplogroup C2a‐M86, the major subbranch of C2a‐M48. Materials and methods: In total, 18 newly generated Y chromosome sequences from C2a‐M48 males and 20 previously available Y‐chromosome sequences from this haplogroup were analyzed. A highly revised phylogenetic tree of haplogroup C2a‐M86 with age estimates was reconstructed. Frequencies of this lineage in the literature were collected and a comprehensive analysis of this lineage in 13 022 individuals from 245 populations in Eurasia was performed. Results: The distribution map of C2a‐M48 indicated the most probable area of origin and diffusion route of this paternal lineage in North Eurasia. Most C2a‐M86 samples from Tungusic‐speaking populations belonged to the sublineage C2a‐F5484, which emerged about 3300 years ago. We identified six unique sublineages corresponding to the Manchu, Evenks, Evens, Oroqen, and Daurpopulations; these sublineages diverged gradually over the past 1900 years. Notably, we observed a clear north‐south dichotomous structure for sublineages derived from C2a‐F5484, consistent with the internal north‐south divergence of Tungusic languages and ethnic groups. Conclusions: We identified the important founding paternal haplogroup, C2a‐F5484, for Tungusic‐speaking populations as well as numerous unique subgroups of this haplogroup. We propose that the timeframe for the divergence of C2a‐F5484 corresponds with the early differentiation of ancestral Tungusic‐speaking populations. [ABSTRACT FROM AUTHOR]

Programmed cell death ligand 1 (PD‐L1), inducing T cell exhaustion to facilitate immune escape of tumor cells, is upregulated by interleukin 6 (IL‐6) in T cell lymphoma and ovarian cancer. The purpose of this study is to investigate the expression of IL‐6 and PD‐L1 in thyroid cancer, and whether IL‐6 regulates PD‐L1 expression. As a result, IL‐6 and PD‐L1 were highly expressed in thyroid cancer tissues. Multivariate logistic analysis showed that tumor size, distant metastasis, and risk stratification were significantly associated with IL‐6 expression (P <.05), and multifocality, lymph node metastasis, distant metastasis, risk stratification, and IL‐6 expression were identified as the independent predictors of PD‐L1 expression (P <.05). The invasiveness of thyroid cancer was significantly enhanced after IL‐6 treatment or PD‐L1 overexpression. PD‐L1 positive rate correlated with IL‐6 expression in cancer tissues (P <.001), and after IL‐6 treatment, the PD‐L1 expression in TPC‐1 and BCPAP significantly increased. The mitogen‐activated protein kinase pathway (MAPK) and the Janus‐activated kinase (JAK)–signal transducers and activators of transcription 3 (STAT3) signaling pathways were activated by IL‐6, and the IL‐6–induced PD‐L1 expression decreased after treatment with these two signaling pathway inhibitors. Knockdown of transcription factors c‐Jun and stat3 suppressed the expression of PD‐L1 induced by IL‐6, and these two factors could bind to PD‐L1 gene promoter directly and promote its transcription. It is concluded that IL‐6 and PD‐L1 are overexpressed in thyroid cancer and are related to tumor invasiveness. IL‐6 upregulates PD‐L1 expression through the MAPK and JAK‐STAT3 signaling pathways, which function via transcription factors c‐Jun and stat3. [ABSTRACT FROM AUTHOR]

Objectives: Subbranches of Y‐chromosome haplogroup C2a‐L1373 are founding paternal lineages in northern Asia and Native American populations. Our objective was to investigate C2a‐L1373 differentiation in northern Asia and its implications for Native American origins. Materials and Methods: Sequences of rare subbranches (n = 43) and ancient individuals (n = 37) of C2a‐L1373 (including P39 and MPB373), were used to construct phylogenetic trees with age estimation by BEAST software. Results: C2a‐L1373 expanded rapidly approximately 17.7,000–14.3,000 years ago (kya) after the last glacial maximum (LGM), generating numerous sublineages which became founding paternal lineages of modern northern Asian and Native American populations (C2a‐P39 and C2a‐MPB373). The divergence pattern supports possible initiation of differentiation in low latitude regions of northern Asia and northward diffusion after the LGM. There is a substantial gap between the divergence times of C2a‐MPB373 (approximately 22.4 or 17.7 kya) and C2a‐P39 (approximately 14.3 kya), indicating two possible migration waves. Discussion We discussed the decreasing time interval of "Beringian standstill" (2.5 ky or smaller) and its reduced significance. We also discussed the multiple possibilities for the peopling of the Americas: the "Long‐term Beringian standstill model," the "Short‐term Beringian standstill model," and the "Multiple waves of migration model." Our results support the argument from ancient DNA analyses that the direct ancestor group of Native Americans is an admixture of "Ancient Northern Siberians" and Paleolithic communities from the Amur region, which appeared during the post‐LGM era, rather than ancient populations in greater Beringia, or an adjacent region, before the LGM. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is characterized by β‐amyloid (Aβ) deposition and Tau phosphorylation, in which its pathogenesis has not been cleared so far. The metabolism of Aβ and Tau is critically affected by the autophagy. Abnormal autophagy is thought to be involved in the pathogenesis of AD, regulating autophagy may become a new strategy for AD treatment. In the early stage of AD, the presence of Aβ and Tau can induce autophagy to promote their clearance by means of mTOR‐dependent and independent manners. As AD progress, the autophagy goes aberrant. As a result, Aβ and Tau generate continually, which aggravates both autophagy dysfunction and AD. Besides, several related genes and proteins of AD can also adapt autophagy to make an effect on the AD development. There seems to be a bi‐directional relationship between AD pathology and autophagy. At present, this article reviews this relationship from these aspects: (a) the signaling pathways of regulating autophagy; (b) the relationships between the autophagy and the processing of Aβ; (c) Aβ and Tau cause autophagy dysfunction; (d) normal autophagy promotes the clearance of Aβ and Tau; (e) the relationships between the autophagy and both genes and proteins related to AD: TFEB, miRNAs, Beclin‐1, Presenilin, and Nrf2; and (f) the small molecules regulating autophagy on AD therapy. All of the above may help to further elucidate the pathogenesis of AD and provide a theoretical basis for clinical treatment of AD. [ABSTRACT FROM AUTHOR]

Obesity is considered a chronic inflammatory disease, the inflammatory factors, such as interleukin 6 (IL‐6), monocyte chemoattractant protein 1 (MCP‐1) and small inducible cytokine A5 (RANTES), are elevated in obese individuals. Pituitary adenylate cyclase‐activating polypeptide (PACAP) suppresses anti‐inflammatory cytokines and ameliorates glucose and lipid metabolism. Our previous study showed that Fas apoptosis inhibitory molecule (FAIM) is a new mediator of Akt2 signalling, increases the insulin signalling pathway and lipid metabolism. In this study, we found that PACAP promoted the expression of FAIM protein in a human hepatocyte cell line (L02). Overexpression of FAIM with lentivirus suppressed the expression of the inflammatory factor interleukin 6 (IL‐6), monocyte chemoattractant protein 1 (MCP‐1) and tumour necrosis factor alpha (TNF‐α). Following treatment of obese mice with FAIM or PACAP for 2 weeks, inflammation was alleviated and the bodyweight and blood glucose levels were decreased. Overexpression of FAIM down‐regulated the expression of adipogenesis proteins, including SREBP1, SCD1, FAS, SREBP2 and HMGCR, and up‐regulated glycogen synthesis proteins, including Akt2 (Ser474) phosphorylation, GLUT2 and GSK‐3β, in the liver of obese mice. However, down‐regulation of FAIM with shRNA promotes obesity. Altogether, our data identified that FAIM mediates the function of PACAP in anti‐inflammation, glucose regulation and lipid metabolism in obese liver. [ABSTRACT FROM AUTHOR]

Primary familial brain calcification (PFBC) is a rare neurological disorder. Mutations in five genes (SLC20A2, PDGFRB, PDGFB, XPR1, and MYORG) have been linked to PFBC. Here, we used SYBR green‐based real‐time quantitative polymerase chain reaction (PCR) assay and denaturing high‐performance liquid chromatography analysis to detect copy number variants (CNVs) in 20 unrelated patients with PFBC, negatively sequenced for the five known genes. We identified three deletions in SLC20A2, including a large de novo full gene deletion and two exonic deletions confined to exon 2 and exon 6, respectively. Subsequent linked‐read whole‐genome sequencing of the patient with the large deletion showed a 1.7 Mb heterozygous deletion which removed the entire coding regions of SLC20A2 as well as 21 other genes. In the family with a deletion of exon 6, a missense variant of uncertain significance (SLC20A2: p.E267Q) also co‐segregated with the disease. Functional assay showed the deletion could result in significantly impaired phosphate transport, whereas the p.E267Q variant did not. Our results confirm that deletion in SLC20A2 is a causal mechanism for PFBC and highlight the importance of functional study for classifying a rare missense variant as (likely) pathogenic. [ABSTRACT FROM AUTHOR]

Primary familial brain calcification (PFBC) is a rare neurodegenerative disorder with four causative genes (SLC20A2, PDGFRB, PDGFB, and XPR1) that have been identified. Here, we aim to describe the mutational spectrum of four causative genes in a series of 226 unrelated Chinese PFBC patients. Mutations in four causative genes were detected in 16.8% (38/226) of PFBC patients. SLC20A2 mutations accounted for 14.2% (32/226) of all patients. Mutations in the other three genes were relatively rare, accounting for 0.9% (2/226) of all patients, respectively. Clinically, 44.8% of genetically confirmed patients (probands and relatives) were considered symptomatic. The most frequent symptoms were chronic headache, followed by movement disorders and vertigo. Moreover, the total calcification score was significantly higher in the symptomatic group compared to the asymptomatic group. Functionally, we observed impaired phosphate transport induced by seven novel missense mutations in SLC20A2 and two novel mutations in XPR1. The mutation p.D164Y in XPR1 might result in low protein expression through an enhanced proteasome pathway. In conclusion, our study further confirms that mutations in SLC20A2 are the major cause of PFBC and provides additional evidence for the crucial roles of phosphate transport impairment in the pathogenies of PFBC. We made a genetic diagnosis in 16.8% of PFBC probands and identified 30 mutations; Mutations in SLC20A2 are the major cause of PFBC, while the other three genes are relatively rare; Our findings also strongly support crucial roles of phosphate transport impairment in the pathogenies of PFBC. [ABSTRACT FROM AUTHOR]

Objective. Perilla frutescens (L.) Brittis is a dietary herbal medicine and has anticancer effect. However, little is known about its anticancer peptides. This study is aimed at identifying cytotoxic oligopeptides which are loaded by a drug delivery system, to explore its anticancer application. Methods. The oligopeptides were isolated from enzymatic hydrolysates of Perilla seed crude protein by using ultrafiltration, gel filtration chromatography, and reversed-phase high-performance liquid chromatography (RP-HPLC). The structure of the oligopeptide was determined using a peptide sequencer, and its anticancer effect was examined by the MTT assay. PSO (Perilla seed oligopeptide), the most potent anticancer oligopeptide, was loaded by chitosan nanoparticles (NPs) modified by hyaluronic acid (HA). Then, the particle size, zeta potential, encapsulation efficiency (EE), drug loading efficiency (LE), the cumulative release rates of NPs, and its cytotoxic effect on cancer cells were investigated. Results. Three fractions were isolated by the chromatography assay. The third fraction has a broad-spectrum and the strongest anticancer effect. This fraction was further purified and identified as SGPVGLW with a molecular weight of 715 Da and named as PSO. Then, PSO was loaded by HA-conjugated chitosan to prepare HA/PSO/C NPs, which had a uniform size of 216.7 nm, a zeta potential of 35.4 mV, an EE of 38.7%, and an LE of 24.3%. HA/PSO/C NPs had a slow release rate in vitro, with cumulative release reaching to 81.1%. Compared with free PSO, HA/PSO/C NPs showed notably enhanced cytotoxicity and had the strongest potency to human glioma cell line U251. Conclusion. This study demonstrated that PSO, a novel oligopeptide from Perilla seeds, has a broad-spectrum anticancer effect and could be encapsulated by NPs, which enhanced tumor targeting cytotoxicity with obvious controlled release. Our study indicates that Perilla seeds are valuable for anticancer peptide development. [ABSTRACT FROM AUTHOR]

Integrin subunit alpha 9 (ITGA9) mediates cell-cell and cell-matrix adhesion, cell migration, and invasion through binding different kinds of extracellular matrix (ECM) components. However, its potential role and underlying molecular mechanisms remain unclear in hepatocellular carcinoma (HCC). Here, we found that ITGA9 expression was obviously decreased in patients with HCC, which was negatively correlated with HCC growth and metastasis. ITGA9 overexpression significantly inhibited cell proliferation and migration in vitro as well as tumor growth and metastasis in vivo. Our data demonstrated that the inhibitory effect of ITGA9 on HCC cell motility was associated with reduced phosphorylation of focal adhesion kinase (FAK) and c-Src tyrosine kinase (Src), disrupted focal adhesion reorganization, and decreased Rac1 and RhoA activity. Our data suggest ITGA9, as a suppressor of HCC, prevents tumor cell migration and invasiveness through FAK/Src-Rac1/RhoA signaling. [ABSTRACT FROM AUTHOR]

Integrin subunit alpha 9 (ITGA9) mediates cell-cell and cell-matrix adhesion, cell migration, and invasion through binding different kinds of extracellular matrix (ECM) components. However, its potential role and underlying molecular mechanisms remain unclear in hepatocellular carcinoma (HCC). Here, we found that ITGA9 expression was obviously decreased in patients with HCC, which was negatively correlated with HCC growth and metastasis. ITGA9 overexpression significantly inhibited cell proliferation and migration in vitro as well as tumor growth and metastasis in vivo. Our data demonstrated that the inhibitory effect of ITGA9 on HCC cell motility was associated with reduced phosphorylation of focal adhesion kinase (FAK) and c-Src tyrosine kinase (Src), disrupted focal adhesion reorganization, and decreased Rac1 and RhoA activity. Our data suggest ITGA9, as a suppressor of HCC, prevents tumor cell migration and invasiveness through FAK/Src-Rac1/RhoA signaling. [ABSTRACT FROM AUTHOR]

Abstract: BACKGROUND: Perilla essential oil (EO) possesses high antioxidant, antimicrobial and insecticidal activities, and has proven to be more reliable than chemically synthesized food preservatives. Nevertheless, EOs have disadvantages of facile photo‐degradation and oxidation, which limit their use in agriculture and food industries. Microencapsulation technology that generates a polymeric coating surrounding EOs could overcome these disadvantages. RESULTS: The EO concentration had a significant effect on encapsulation efficiency (EE) and loading capacity (LC). The best encapsulation conditions were obtained with 2% v/v EO, for which EE and LC were 57% and 36%, respectively. EO‐loaded microspheres exhibited a crimped surface with phanic lumps by scanning electron microscopy. Thermal stability experiments revealed droplets that began to decompose sharply at 108 °C, with a 61% weight, loss, which was much lower than EOs of 98%. EO‐loaded microcapsules demonstrated good antibacterial activity. Strawberry preservation studies showed that EO‐loaded microcapsules could significantly inhibit strawberry decay, maintain the quality of strawberries and prolong shelf life. CONCLUSION: Perilla EO‐loaded microcapsules were successfully prepared by ionic gelation and were effective at inhibiting several bacterial strains. EO–alginate microcapsules could effectively delay the volatilization of EO. Perilla EO‐loaded microcapsules therefore have potential for use as an antimicrobial and preservative agent in the food industry. © 2017 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

A bibliometric approach to assess trends in global tea research using literature in the Science Citation Index Expanded database from 1991 to 2014 has been conducted. Articles were analysed by scientific output and research performances of countries and institutions. The distribution of keywords in the articles' titles, author-supplied keywords and KeyWords Plus as well as citation and publication trends of tea-related articles was used to evaluate the research trends. The research output devoted to tea science increased greatly after the year 2002 indicating a paradigm shift that demonstrated that researchers became increasingly keen on biochemical relevance of active compounds in tea in mitigating emergent health challenges over classical tea research. [ABSTRACT FROM AUTHOR]

A dual-Förster resonance energy transfer (FRET)-based versatile prodrug (V-prodrug), in which the fluorescence of both 5(6)-carboxylfluorescein (FAM) and doxorubicin (DOX) can be quenched by 4-(dimethylaminoazo)benzene-4-carboxylic acid (Dabcyl) with high quenching efficiency, is developed in this paper. The V-prodrug can selectively bind to the αvβ3 integrin overexpressed cancer cells through the Arg-Gly-Asp (RGD) targeting moiety. After that, the acid-mediated DOX release of the V-prodrug can be real-time monitored by the increase of the red fluorescence from DOX. Thereafter, DOX-induced cell apoptosis can also be in situ assessed by the fluorescence recovery of the FAM, due to the caspase-3-mediated Asp-Glu-Val-Asp (DEVD) peptide sequence cleavage. This novel prodrug provides a cascaded imaging of real-time drug release and subsequent cell apoptosis, which enables the in situ detection of the cancer response and the therapeutic efficacy evaluation of the prodrug. [ABSTRACT FROM AUTHOR]

In order to enhance the capabilities of knowledge service in product innovation design service platform, a method of acquiring knowledge resources supporting for product innovation from the Internet and providing knowledge active push is proposed. Through knowledge modeling for product innovation based on ontology, the integrated architecture of knowledge resources network is put forward. The technology for the acquisition of network knowledge resources based on focused crawler and web services is studied. Knowledge active push is provided for users by user behavior analysis and knowledge evaluation in order to improve users’ enthusiasm for participation in platform. Finally, an application example is illustrated to prove the effectiveness of the method. [ABSTRACT FROM AUTHOR]

In this study, a pH sensitive chimeric peptide is developed to codeliver a photosensitizer, protoporphyrin IX (PpIX), and plasmid DNA simultaneously. In the presence of matrix metalloproteinase-2 (MMP-2), the chimeric peptide undergoes the process of hydrolysis of PLGVR peptide sequence, exfoliation of PEG, and increase of positive charges. As a result, the chimeric peptide can be preferentially uptaken by MMP-2 rich tumor cells. To realize synergistic effect of drug and gene delivery, a dual-stage light irradiation strategy is developed, i.e., the short time light irradiation can efficiently enhance the endosomal escape of the chimeric peptide/PpIX/DNA complexes by the formation the reactive oxygen species (ROS), resulting in synergistic endosomal escape and improved DNA expression. In addition, due to the screened phototoxicity of PpIX, short time light irradiation does not lead to detectable changes in the cell viability. After the gene transfection, the screened phototoxicity of PpIX is subsequently stimulated by long time irradiation to achieve high synergistic efficacy of photodynamic and gene therapies. Both in vitro and in vivo studies confirm the chimeric peptide-based nanocarrier with a good synergistic effect is a promising nanoplatform for tumor treatments. [ABSTRACT FROM AUTHOR]

Peroxiredoxin 3 (Prx3) is a mitochondrial member of the antioxidant family of thioredoxin peroxidases that uses mitochondrial thioredoxin 2 as a source of reducing equivalents to scavenge hydrogen peroxide (H 2 O 2 ). Here, we report that the protein levels of Prx3 are significantly reduced in VHL-deficient clear cell renal cell carcinoma (CCRCC). Furthermore, stabilization of HIF-1α protein, caused either by VHL deficiency under normoxia, or by hypoxia, significantly reduced Prx3 expression. Luciferase-reporter and chromatin-immunoprecipitation assays indicated that HIF-1α binds to the hypoxia-responsive elements of PRDX3 promoter and represses its transcription. Finally, shRNA-based assays suggested that Prx3 downregulation is required for the HIF-1α-dependent proliferation of CCRCC cells. Taken together, our results shed new light onto the mechanism of HIF-1α-dependent proliferation in CCRCC cells. [ABSTRACT FROM AUTHOR]

Angiosarcomas account for a mere 2-3% of adult soft tissue sarcomas, with an overall poor outcome. Depending on the primary site, angiosarcomas have distinct prognosis. Primary hepatic angiosarcomas ( PHAs) are much rare tumors, with worse prognosis compared with other angiosarcomas. PHA is reported to be associated with vinyl chloride, but the majority of patients were still with unknown etiology. As PHA lacks specific symptoms, signs, or images, pathological diagnosis is necessary. The review summarizes 25 articles published from January 2000 to December 2012, including 64 cases of PHA with detailed information. Survival curves are estimated using the Kaplan- Meier method by SPSS 21.0. We find that the median survival time is 5 months; local excision alone or combination with adjuvant therapy is the optimal choice, with median survival time of 17 months. In addition, liver transplant is abandoned for high recurrence rate; emergent transcatheter arterial embolization is thought to be an efficient method for controlling intra-abdominal bleeding; and transcatheter arterial chemoembolization and chemotherapy may be helpful in improving survival. [ABSTRACT FROM AUTHOR]