Biphasic co-detection of melanoma aneuploid tumor cells and tumor endothelial cells in guidance of specifying the field cancerized surgical excision margin and administering immunotherapy.

An optimum safety excision margin (EM) delineated by precise demarcation of field cancerization along with reliable biomarkers that enable predicting and timely evaluating patients' response to immunotherapy significantly impact effective management of melanoma. In this study, optimized biphasic "immunofluorescence staining integrated with fluorescence insitu hybridization" (iFISH) was conducted along the diagnosis-metastasis-treatment-cellular MRD axis to longitudinally co-detect a full spectrum of intact CD31- aneuploid tumor cells (TCs), CD31+ aneuploid tumor endothelial cells (TECs), viable and necrotic circulating TCs (CTCs) and circulating TECs (CTECs) expressing PD-L1, Ki67, p16 and Vimentin in unsliced specimens of the resected primary tumor, EM, dissected sentinel lymph nodes (SLNs) and peripheral blood in an early-stage melanoma patient. Numerous PD-L1+ aneuploid TCs and TECs were detected at the conventional safety EM (2 cm), quantitatively indicating the existence of a field cancerized EM for the first time. Contrary to highly heterogeneous PD-L1 expression and degrees of Chr8 aneuploidy in TCs and TECs in the primary lesions as well as CTCs and CTECs in peripheral blood, almost all TCs and TECs in SLNs and EM were homogeneously PD-L1+ haploid cells. Dynamic monitoring and cellular MRD assessment revealed that, in contrast to PD-L1+ CTCs being responsive to the immune checkpoint inhibitor (ICI-anti-PD-1), multiploid (≥pentasomy 8) PD-L1+ and Ki67+ CTECs were respectively resistant to ICI-sensitized T cells. In therapeutically stressed lymphatic and hematogenous metastatic cascades, stratified phenotypic and karyotypic profiling of iFISH tissue and liquid biopsied TCs, TECs, CTCs and CTECs in future large-cohort studies will enable appropriate re-specification of the optimal safety EM and distribution mapping of in-depth characterized, subcategorized target cells to help illustrate their metastatic relevance, ultimately improving risk stratification and clinical intervention of tumor progression, metastases, therapy resistance and cancer relapse.

Molecular phylogeny of Hesperiidae (Lepidoptera) with an emphasis on Asian and African genera.

Despite considerable research efforts in recent years, the deeper phylogenetic relationships among skipper butterflies (Hesperiidae) remain unresolved. This is primarily because of limited sampling, especially within Asian and African lineages. In this study, we consolidated previous data and extensively sampled Asian and African taxa to elucidate the phylogenetic relationships within Hesperiidae. The molecular dataset comprised sequences from two mitochondrial and two nuclear gene regions from 563 species that represented 353 genera. Our analyses revealed seven subfamilies within Hesperiidae: Coeliadinae, Euschemoninae, Eudaminae, Pyrginae, Heteropterinae, Trapezitinae, and Hesperiinae. The systematics of most tribes and genera aligned with those of prior studies. However, notable differences were observed in several tribes and genera. Overall, the position of taxa assigned to incertae sedis in Hesperiinae is largely clarified in this study. Our results strongly support the monophyly of the tribe Tagiadini (Pyrginae), and the systematics of some genera are clarified with comprehensive discussion. We recognize 15 tribes within the subfamily Hesperiinae. Of these, nine tribes are discussed in detail: Aeromachini, Astictopterini, Erionotini, Unkanini (new status), Ancistroidini, Ismini (confirmed status), Plastingini (new status), Gretnini (confirmed status), and Eetionini (confirmed status). We propose four subtribes within Astictopterini: Hypoleucina subtrib.n., Aclerosina, Cupithina, and Astictopterina. Furthermore, we describe a new genus (Hyarotoidesgen.n.) and reinstate two genera (Zeareinst.stat. and Separeinst.stat.) as valid. Additionally, we propose several new combinations: Zea mythecacomb.n.,Sepa bononiacomb.n. & reinst.stat., and Sepa umbrosacomb.n. This study, with extensive sampling of Asian and African taxa, greatly enhances the understanding of the knowledge of the skipper tree of life.

Nonreciprocal reflection based on asymmetric graphene metasurfaces.

We propose a scheme to achieve controllable nonreciprocal behavior in asymmetric graphene metasurfaces composed of a continuous graphene sheet and a poly crystalline silicon slab with periodic grooves of varying depths on each side. The proposed structure exhibits completely asymmetric reflection in opposite directions in the near-infrared range, which is attributed to the pronounced structural asymmetry and its accompanying nonlinear effects. The obtained nonreciprocal reflection ratio, reaching an impressive value of 21.27 dB, combined with a minimal insertion loss of just -0.76 dB, highlights the remarkable level of nonreciprocal efficiency achieved by this design compared to others in its category. More importantly, the proposed design can achieve dynamic tunability by controlling the incident field intensity and the graphene Fermi level. Our design highlights a potential means for creating miniaturized and integratable nonreciprocal optical components in reflection mode, which can promote the development of the integrated isolators, optical logic circuits, and bias-free nonreciprocal photonics.

Liver-Specific Ionizable Lipid Nanoparticles Mediated Efficient RNA Interference to Clear "Bad Cholesterol".

Background: High-level low-density lipoprotein cholesterol (LDL-C) plays a vital role in the development of atherosclerotic cardiovascular disease. Low-density lipoprotein receptors (LDLRs) are scavengers that bind to LDL-C in the liver. LDLR proteins are regulated by proprotein convertase subtilisin/kexin type 9 (PCSK9), which mediates the degradation of LDLR and adjusts the level of the plasma LDL-C. The low expression of PCSK9 leads to the up-regulation of liver LDLRs and the reduction of plasma LDL-C. Hepatocytes are attractive targets for small interfering RNA (siRNA) delivery to silence Pcsk9 gene, due to their significant role in LDL-C regulation. Methods: Here, a type of liver-specific ionizable lipid nanoparticles is developed for efficient siRNA delivery. This type of nanoparticles shows high stability, enabling efficient cargo delivery specifically to hepatocytes, and a membrane-active polymer that reversibly masks activity until an acidic environment is reached. Results: Significantly, the siPcsk9 (siRNA targeting to Pcsk9)-loaded nanoparticles (GLP) could silence 90% of the Pcsk9 mRNA in vitro. In vivo study showed that the improved accumulation of GLP in the liver increased LDLR level by 3.35-fold and decreased plasma LDL-C by 35%. Conclusion: GLP has shown a powerful effect on reducing LDL-C, thus providing a potential therapy for atherosclerotic cardiovascular disease.

Application of starch degrading bacteria from tobacco leaves in improving the flavor of flue-cured tobacco.

Starch is an essential factor affecting the quality of flue-cured tobacco, and high starch content can affect the sensory quality and safety. Recently, the degradation of macromolecules in tobacco raw materials by using additional microorganisms to improve their intrinsic quality and safety has become a new research hotspot in the tobacco industry. However, the technical maturity and application scale are limited. Our study analyzed the correlation between microbial community composition and volatile components on the surface of tobacco leaves from 14 different grades in Fujian tobacco-producing areas. The PICRUSt software was utilized to predict the function of the microbial community present in tobacco leaves. Furthermore, dominant strains that produced amylase were screened out, and an enzyme solution was prepared to enhance the flue-cured tobacco flavor. Changes in the content of macromolecules and volatile components were determined, and sensory evaluations were conducted to assess the overall quality of the tobacco leaves. The results showed that the dominant bacterial genera on the surface of Fujian tobacco leaves were Variovorax, Sphingomonas, Bacillus, etc. Bacillus was positively correlated with various volatile components, which contributed to the sweet and aromatic flavors of Fujian flue-cured tobacco. The main genetic functions of Fujian flue-cured tobacco surface bacteria were carbohydrate metabolism and amino acid metabolism. After treating flue-cured tobacco with an enzyme preparation prepared by the fermentation of Paenibacillus amylolyticus A17 #, the content of starch, pectin, and cellulose in flue-cured tobacco decreased significantly compared with the control group. Meanwhile, the content of total soluble sugar and reducing sugar was significantly increased, and the volatile aroma components, such as 3-hydroxy--damascone, 2,3-dihydro-3,5-dihydroxy-6-methyl-4 H-Pyran-4-one, ethyl palmitate, ethyl linolenic acid, etc., were significantly increased. The aroma quality and quantity of flue-cured tobacco were enhanced, while impurities were reduced. The smoke characteristics were improved, with increased fineness, concentration, and moderate strength. The taste characteristics were also improved, with reduced irritation and a better aftertaste. In conclusion, Bacillus, as the dominant genus in the abundance of bacterial communities on tobacco surfaces in Fujian, had an essential impact on the flavor of tobacco leaves by participating in carbohydrate metabolism and finally forming the unique flavor style of flue-cured tobacco in Fujian tobacco-producing areas. Paenibacillus amylolyticus A17 #, a target strain with amylase-producing ability, was screened from the surface of Fujian flue-cured tobacco. The enzyme preparation, produced by the fermentation of Paenibacillus amylolyticus A17 #, was utilized to reduce the content of macromolecules, increase the content of water-soluble total sugar and reducing sugar, and produce a variety of crucial volatile aroma components, which had a significant improvement on the quality of tobacco leaves.

Fucose ameliorates the proinflammatory property of Fusobacterium nucleatum in colitis via altering its metabolism.

Introduction: Previous studies reported that fucose plays a protective role in inhibiting pathogens. Fusobacterium nucleatum (Fn) was recently found to promote the progression of colitis. However, the effects of fucose on Fn are poorly understood. This study aimed to explore whether fucose could ameliorate the proinflammatory property of Fn in colitis and the underlying mechanisms. Methods: To validate our hypothesis, mice were administrated with Fn and fucose-treated Fn (Fnf) before dextran sulfate sodium (DSS) treatment to establish Fn related colitis model. The metabolism variation of Fn was detected by metabolomic analysis. To verify the effects of bacterial metabolites on intestinal epithelial cells (IECs), Caco-2 cells were treated with bacterial supernatant. Results: More severe inflammation, intestinal barrier damage, autophagy block, and apoptosis in the colon were noted in DSS mice that were administrated with Fn or Fnf. However, the severity degree in Fnf+DSS group was less compared to Fn+DSS group. Metabolic pathways of Fn were altered after fucose treatment and proinflammatory metabolites were decreased. The supernatant of Fnf induced a lower level of inflammation than Fn in Caco-2 cells. One of the decreased metabolites, homocysteine thiolactone (HT), was proven to induce inflammatory effects in Caco-2 cells. Discussion: In conclusion, fucose ameliorates the proinflammatory property of Fn via altering its metabolism and these findings provide evidence for the application of fucose as functional food or prebiotic in the treatment of Fn related colitis.

Dehydration kinetics and mechanism of the stable isonicotinamide hydrate revealed by terahertz spectroscopy and DFT calculation.

The dehydration behavior of pharmaceutical hydrates has a great influence on its physiochemical properties such as stability, dissolution rate and bioavailability. However, how the intermolecular interactions vary during dehydration process remains elusive. In this work, we employed terahertz time-domain spectroscopy (THz-TDS) to probe the low-frequency vibrations and the dehydration process of isonicotinamide hydrate I (INA-H I). Theoretical solid-state DFT calculation was conducted to reveal its mechanism. Vibrational modes which are responsible for the THz absorption peaks were decomposed for better understanding the characters of these low-frequency modes. The result suggests translational motion is the dominant component for water molecules in THz region. Evolution of the THz spectrum of INA-H I during dehydration provides direct evidence of the variations of crystal structure. Based on the THz measurements, a two-step kinetics mode including first-rate reaction and three-dimensional nuclei growth is proposed. And we figure that the low-frequency vibrations of water molecules are the origin of dehydration process of hydrate.

Cell Membrane-Camouflaged Nanoparticles Mediated Nucleic Acids Delivery.

Nucleic acids have emerged as promising therapeutic agents for many diseases because of their potential in modulating gene expression. However, the delivery of nucleic acids remains a significant challenge in gene therapy. Although viral vectors have shown high transfection efficiency, concerns regarding teratogenicity or carcinogenicity have been raised. Non-viral vehicles, including cationic polymers, liposomes, and inorganic materials possess advantages in terms of safety, ease of preparation, and low cost. Nevertheless, they also face limitations related to immunogenicity, quick clearance in vivo, and lack of targeting specificity. On the other hand, bioinspired strategies have shown increasing potential in the field of drug delivery, yet there is a lack of comprehensive reviews summarizing the rapid development of bioinspired nanoparticles based on the cell membrane camouflage to construct the nucleic acids vehicles. Herein, we enumerated the current difficulties in nucleic acid delivery with various non-viral vehicles and provided an overview of bioinspired strategies for nucleic acid delivery.

Boosting the activity and stability via synergistic catalysis of Co nanoparticles and MoC to construct a bifunctional electrocatalyst for high-performance and long-life rechargeable zinc-air batteries.

The high overpotential of the oxygen reduction reaction (ORR) and the oxygen evolution reaction (OER) leading to slow air cathode kinetics is still a major challenge for zinc-air batteries (ZABs), hindering the commercialization of ZABs. With the advantages of cost-effectiveness and feasibility of synthesis at room temperature, zeolite imidazole frameworks (ZIFs) are regarded as advanced precursors. But a majority of ZIF-derived catalysts show only one catalytic activity, which limits their performance in ZABs as well as the cycling stability. In addition, molybdenum carbide (MoC) is recognized as an excellent candidate for renewable energy conversion due to its good chemical resistance and thermal stability. Herein, we report a ZIF-67-derived Co/MoC-NC multiphase doped carbon bifunctional ORR/OER catalyst with multiple active sites for the cathode of ZABs. The synergistic catalysis of Co nanoparticles and MoC nanoparticles in Co/MoC-NC which are embedded in a thin layer of N-doped graphitic carbon and immobilized on N-doped graphitic carbon, respectively, demonstrates superior ORR catalytic performance and durability both under alkaline and acidic conditions (E1/2 = 0.87 V in 1.0 M KOH and E1/2 = 0.76 V in 0.5 M H2SO4). Simultaneously, Co/MoC-NC also exhibits favorable OER performance (10 mA cm-2, η = 320 mV) in 1 M KOH. Furthermore, a remarkable peak-power density of 215.36 mW cm-2 and great cycling stability could be achieved while applying Co/MoC-NC in the cathode of ZABs (over 300 h). This work will provide a viable design concept for designing and synthesizing multifunctional catalysts to construct rechargeable ZABs.

Insights into Allosteric Mechanisms of the Lung-Enriched p53 Mutants V157F and R158L.

Lung cancer is a leading fatal malignancy in humans. p53 mutants exhibit not only loss of tumor suppressor capability but also oncogenic gain-of-function, contributing to lung cancer initiation, progression and therapeutic resistance. Research shows that p53 mutants V157F and R158L occur with high frequency in lung squamous cell carcinomas. Revealing their conformational dynamics is critical for developing novel lung therapies. Here, we used all-atom molecular dynamics (MD) simulations to investigate the effect of V157F and R158L substitutions on the structural properties of the p53 core domain (p53C). Compared to wild-type (WT) p53C, both V157F and R158L mutants display slightly lesser ß-sheet structure, larger radius of gyration, larger volume and larger exposed surface area, showing aggregation-prone structural characteristics. The aggregation-prone fragments (residues 249-267 and 268-282) of two mutants are more exposed to water solution than that of WT p53C. V157F and R158L mutation sites can affect the conformation switch of loop 1 through long-range associations. Simulations also reveal that the local structure and conformation around the V157F and R158L mutation sites are in a dynamic equilibrium between the misfolded and properly folded conformations. These results provide molecular mechanistic insights into allosteric mechanisms of the lung-enriched p53 mutants.

Metagenomic insight into the microbial degradation of organic compounds in fermented plant leaves.

Microbial degradation of organic compounds is an environmentally benign and energy efficient part in product processing. Fermentation of plant leaves involves enzymatic actions of many microorganisms. However, microbes and enzymes discovered from natural degradation communities were still limited by cultural methods. In this study, we used a metagenomics sequence-guided strategy to identify the microbes and enzymes involved in compound degradation and explore the potential synergy among community members in fermented tobacco leaves. The results showed that contents of protein, starch, pectin, lignin, and cellulose varied in fermented leaves from different growing sites. The different compound contents were closely related to taxonomic composition and functional profiles of foliar microbial communities. Microbial communities showed significant correlations with protein, lignin, and cellulose. Vital species for degradations of protein (Bacillus cereus and Terribacillus aidingensis), lignin (Klebsiella pneumoniae and Pantoea ananatis) and cellulose (Pseudomonas putida and Sphingomonas sp. Leaf20) were identified and relating hydrolytic enzymes were annotated. Further, twenty-two metagenome-assembled genomes (MAGs) were assembled from metagenomes and six potential cellulolytic genomes were used to reconstruct the cellulose-degrading process, revealing the potential metabolic cooperation related to cellulose degradation. Our work should deepen the understanding of microbial roles in plant fermentation and provide a new viewpoint for applying microbial consortia to convert plant organic components to small molecules.

Topological Refraction in Kagome Split-Ring Photonic Insulators.

A valley-Hall-like photonic insulator based on C3v Kagome split-ring is proposed. Theoretical analysis and numerical calculations illustrate that C3v symmetry can be broken not only by global rotation α but also individual rotation θ of the split rings, providing topological phase transitions. Furthermore, refraction of the edge state from the interface into the background space at Zigzag termination is explored. It is shown that positive/negative refraction of the outgoing beam depends on the type of valley (K or K'), from which the edge state is projected. These results provide a new way to manipulate terahertz wave propagation and facilitate the potential applications in directional collimation, beam splitting, negative refraction image, etc.

Temperature-Dependent Terahertz Spectra of Isonicotinamide in the Form I Studied Using the Quasi-Harmonic Approximation.

Anharmonicity of molecular vibrational motions is closely associated with the thermal property of crystals. However, the origin of anharmonicity is still not fully understood. Low-frequency vibrations, which are usually defined in the terahertz (THz) range, show excellent sensitivity to anharmonicity. In this work, anharmonicity of isonicotinamide in the form I was investigated by using temperature-dependent terahertz time-domain spectroscopy and the quasi-harmonic approximation (QHA) approach at PBE-D3 and PBE-MBD levels. Both DFT calculations suggest the variation of π-π stacking conformation dominates in the thermal expansion of the unit cell. Frequency shifts of the modes in THz range obtained by QHA approach are found to be qualitatively consistent with experimental observations, demonstrating QHA approach is a useful tool for the interpretation of frequency shifts of modes induced by temperature.

Co-composting of fresh tobacco leaves and soil: an exploration on the utilization of fresh tobacco waste in farmland.

A large amount of fresh tobacco waste with high water content are produced in farmland, and it may cause environmental pollution if it is not properly treated. The fresh tobacco waste is not easily collected and transported, resulting in its centralized treatment is expensive. This study is to clarify whether it is feasible to treat fresh tobacco wastes by co-composting of them and soil in farmland and applied the obtained compost product into the soil instead of a part of tobacco-specific fertilizer. The results showed that, compared with that in original soil, the relative abundance of Pseudomonas, Azotobacter, and Coprinus of the co-composted products increased by roughly 244%, 323%, and 675%, respectively, and effective nitrogen and available potassium increased by roughly 157% and 132%, respectively. In addition, the nicotine content in co-composted products decreased dramatically compared with the discarded tobacco leaves. The application of the co-composted products and 20% fertilizer amount (15 g/plant) (YD5) exhibited the highest relative abundance of beneficial microbial communities in the soil and the best growth of tobacco plants. The co-composting of fresh tobacco waste and soil in farmland is an effective measure to treat the fresh tobacco waste, and its products increased beneficial microorganisms and stimulate the growth of tobacco plants by replacing an amount of the fertilizer.

Molecular dynamics study on the inhibition mechanisms of ReACp53 peptide for p53-R175H mutant aggregation.

p53 mutant aggregation can lead to loss-of-function (LoF), dominant-negative (DN) and gain-of-function (GoF) effects, involving in tumor growth. Finding inhibition methods of p53 mutant aggregation is a key step for developing new therapeutics against aggregation-associated cancers. Recent studies have shown that a cell-permeable peptide, ReACp53, can inhibit aggregation of the p53 mutant and restore p53 nuclear function as a transcriptional factor, showing extraordinary therapeutic potential. However, the molecular mechanism underlying the inhibition of p53 mutant aggregation by the ReAp53 peptide is unclear. In this work, we used all-atom molecular dynamics (MD) simulations to investigate the effect of ReACp53 peptide on the structural and dynamic properties of the p53 core domain (p53C) of the aggregation-prone R175H mutant. Our simulations revealed that the ReACp53 peptide can stabilize the ordered secondary structure and decrease the flexibility of disordered loops of the R175H mutant through increasing the intra-interactions of p53C. Moreover, we found that ReACp53 peptide specifically binds to the fragment (residues 180-233) of the R175H mutant through strong hydrophobic interactions with residues L188 and L201 and a salt bridge or hydrogen bond formation with residues D186, E198, D204, E221 and E224. The specific binding pattern protects the aggregation-prone fragment (residues 182-213) from exposure to water. Hence, we suggested that the ReACp53 peptide inhibits aggregation of the R175H mutant by restoring the wild-type conformation from an aggregation-prone state and reducing the exposure of the aggregation-prone segment. These results provide molecular mechanistic insight into inhibition of the ReACp53 peptide on amyloid aggregation of the R175H mutant.

Missense Variant of Endoplasmic Reticulum Region of WFS1 Gene Causes Autosomal Dominant Hearing Loss without Syndromic Phenotype.

OBJECTIVE: Genetic variants in the WFS1 gene can cause Wolfram syndrome (WS) or autosomal dominant nonsyndromic low-frequency hearing loss (HL). This study is aimed at investigating the molecular basis of HL in an affected Chinese family and the genotype-phenotype correlation of WFS1 variants. METHODS: The clinical phenotype of the five-generation Chinese family was characterized using audiological examinations and pedigree analysis. Target exome sequencing of 129 known deafness genes and bioinformatics analysis were performed among six patients and four normal subjects to screen suspected pathogenic variants. We built a complete WFS1 protein model to assess the potential effects of the variant on protein structure. RESULTS: A novel heterozygous pathogenic variant NM_006005.3 c.2020G>T (p.Gly674Trp) was identified in the WFS1 gene, located in the C-terminal domain of the wolframin protein. We further showed that HL-related WFS1 missense variants were mainly concentrated in the endoplasmic reticulum (ER) domain. In contrast, WS-related missense variants are randomly distributed throughout the protein. CONCLUSIONS: In this family, we identified a novel variant p.Gly674Trp of WFS1 as the primary pathogenic variant causing the low-frequency sensorineural HL, enriching the mutational spectrum of the WFS1 gene.

Auto-classification of biomass through characterization of their pyrolysis behaviors using thermogravimetric analysis with support vector machine algorithm: case study for tobacco.

BACKGROUND: During the biomass-to-bio-oil conversion process, many studies focus on studying the association between biomass and bio-products using near-infrared spectra (NIR) and chemical analysis methods. However, the characterization of biomass pyrolysis behaviors using thermogravimetric analysis (TGA) with support vector machine (SVM) algorithm has not been reported. In this study, tobacco was chosen as the object for biomass, because the cigarette smoke (including water, tar, and gases) released by tobacco pyrolysis reactions decides the sensory quality, which is similar to biomass as a renewable resource through the pyrolysis process. RESULTS: SVM algorithm has been employed to automatically classify the planting area and growing position of tobacco leaves using thermogravimetric analysis data as the information source for the first time. Eighty-eight single-grade tobacco samples belonging to four grades and eight categories were split into the training, validation, and blind testing sets. Our model showed excellent performances in both the training and validation set as well as in the blind test, with accuracy over 91.67%. Throughout the whole dataset of 88 samples, our model not only provides precise results on the planting area of tobacco leave, but also accurately distinguishes the major grades among the upper, lower, and middle positions. The error only occurs in the classification of subgrades of the middle position. CONCLUSIONS: From the case study of tobacco, our results validated the feasibility of using TGA with SVM algorithm as an objective and fast method for auto-classification of tobacco planting area and growing position. In view of the high similarity between tobacco and other biomasses in the compositions and pyrolysis behaviors, this new protocol, which couples the TGA data with SVM algorithm, can potentially be extrapolated to the auto-classification of other biomass types.

Dynamic control of magnetization spot arrays with three-dimensional orientations.

We report a new paradigm for achieving magnetization spot arrays with controllable three-dimensional (3D) orientations. Toward this aim, we subtly design a tailored incident beam containing three parts and further demonstrate that the designed incident beam is phase-modulated radial polarization. Based on the raytracing model under tight focusing condition and the inverse Faraday effect on the magneto-optic (MO) film, the magnetization field components along the y-axis and z-axis directions are generated through the focus. In particular, we are able to garner orientation-tunable 3D magnetization under different numerical apertures of the focusing objectives by adjusting the ratios between the three parts of incident beam. Apart from a single magnetization spot, magnetization spot arrays capable of dynamically controlling 3D orientation in each spot can also be achieved by multi-zone plate (MZP) phase filter. Such a robust magnetization pattern is attributed to not only the constructive interferences of three orthogonal focal field components, but also the position translation of each magnetization spot resulting from shifting phase of the MZP phase filter. It is expected that the research outcomes can be beneficial to spintronics, magnetic encryption and multi-value MO parallelized storage.

L-fucose ameliorates the carcinogenic properties of Fusobacterium nucleatum in colorectal cancer.

Fusobacterium nucleatum (Fn) is considered a promoting factor in colorectal cancer (CRC); however, only a few studies have investigated therapies against Fn. L-fucose is a natural monosaccharide that has prebiotic potential. The present study aimed to investigate the effect of L-fucose on the carcinogenic properties of Fn. The HCT116 and SW480 colon cancer cell lines were treated with Fn and Fn+L-fucose (Fnf), respectively. The Cell Counting Kit-8 (CCK-8), colony formation, Transwell migration and invasion and wound healing assays were performed to assess the proliferative, migratory and invasive abilities of the cells, respectively. Western blot was performed to detect the protein levels of jak/stat3 pathway components and EMT. The results of the CCK-8, colony formation, Transwell and wound healing assays demonstrated that treatment with Fn significantly enhanced the proliferative, migratory and invasive abilities of HCT116 and SW480 colon cancer cells. Notably, these effects were significantly reversed following addition of L-fucose. Furthermore, L-fucose inhibited the carcinogenic properties of Fn to activate the stat3 pathway and epithelial-to-mesenchymal transition. Taken together, the results of the present study suggest that L-fucose ameliorates the carcinogenic properties of Fn in vitro, and thus may serve as a novel therapeutic target for flora-related colon cancer.

Shared paternal ancestry of Han, Tai-Kadai-speaking, and Austronesian-speaking populations as revealed by the high resolution phylogeny of O1a-M119 and distribution of its sub-lineages within China.

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.