Limb development genes underlie variation in human fingerprint patterns.

Fingerprints are of long-standing practical and cultural interest, but little is known about the mechanisms that underlie their variation. Using genome-wide scans in Han Chinese cohorts, we identified 18 loci associated with fingerprint type across the digits, including a genetic basis for the long-recognized "pattern-block" correlations among the middle three digits. In particular, we identified a variant near EVI1 that alters regulatory activity and established a role for EVI1 in dermatoglyph patterning in mice. Dynamic EVI1 expression during human development supports its role in shaping the limbs and digits, rather than influencing skin patterning directly. Trans-ethnic meta-analysis identified 43 fingerprint-associated loci, with nearby genes being strongly enriched for general limb development pathways. We also found that fingerprint patterns were genetically correlated with hand proportions. Taken together, these findings support the key role of limb development genes in influencing the outcome of fingerprint patterning.

From musk to body odor: Decoding olfaction through genetic variation.

The olfactory system combines input from multiple receptor types to represent odor information, but there are few explicit examples relating olfactory receptor (OR) activity patterns to odor perception. To uncover these relationships, we performed genome-wide scans on odor-perception phenotypes for ten odors in 1000 Han Chinese and validated results for six of these odors in an ethnically diverse population (n = 364). In both populations, consistent with previous studies, we replicated three previously reported associations (ß-ionone/OR5A1, androstenone/OR7D4, cis-3-hexen-1-ol/OR2J3 LD-band), but not for odors containing aldehydes, suggesting that olfactory phenotype/genotype studies are robust across populations. Two novel associations between an OR and odor perception contribute to our understanding of olfactory coding. First, we found a SNP in OR51B2 that associated with trans-3-methyl-2-hexenoic acid, a key component of human underarm odor. Second, we found two linked SNPs associated with the musk Galaxolide in a novel musk receptor, OR4D6, which is also the first human OR shown to drive specific anosmia to a musk compound. We noticed that SNPs detected for odor intensity were enriched with amino acid substitutions, implying functional changes of odor receptors. Furthermore, we also found that the derived alleles of the SNPs tend to be associated with reduced odor intensity, supporting the hypothesis that the primate olfactory gene repertoire has degenerated over time. This study provides information about coding for human body odor, and gives us insight into broader mechanisms of olfactory coding, such as how differential OR activation can converge on a similar percept.

Pulsed Ho:YLF laser intra-cavity pumped by a diode-pumped Q-switched Tm:YAP laser.

We reported an intra-cavity pumped Q-switched laser with dual-wavelength synchronous output at 2066.7 nm and 1940nm. Ho:YLF crystal was pumped by a self-Q-switched Tm:YAP laser, which was served as both a gain medium and a saturable absorber simultaneously. For Ho:YLF laser, under 11.4-W incident pump power, a stable pulse laser was achieved at 2066.7 nm with the highest peak power of 69.65 W and the pulse repetition rate of 42.14 kHz. Under the same incident pump power, the highest peak power and pulse repetition rate of Tm:YAP laser were 17.85 W and 50.82 kHz, corresponding to the central wavelength of 1940nm. These results suggested that Q-switching without additional absorber element were effective way to obtain high-efficiency and compact 2.1 µm pulsed laser.

Advances in the metabolic engineering of Saccharomyces cerevisiae and Yarrowia lipolytica for the production of ß-carotene.

ß-Carotene is one kind of the most important carotenoids. The major functions of ß-carotene include the antioxidant and anti-cardiovascular properties, which make it a growing market. Recently, the use of metabolic engineering to construct microbial cell factories to synthesize ß-carotene has become the latest model for its industrial production. Among these cell factories, yeasts including Saccharomyces cerevisiae and Yarrowia lipolytica have attracted the most attention because of the: security, mature genetic manipulation tools, high flux toward carotenoids using the native mevalonate pathway and robustness for large-scale fermentation. In this review, the latest strategies for ß-carotene biosynthesis, including protein engineering, promoters engineering and morphological engineering are summarized in detail. Finally, perspectives for future engineering approaches are proposed to improve ß-carotene production.

Morphological and physiological response of amphibious Rotala rotundifolia from emergent to submerged form.

Rotala rotundifolia is an amphibious aquatic plant that can live in submerged and emergent forms. It is superior in nitrogen and phosphorus removal. To elucidate its adaptation strategies from emergent to submerged conditions, phenotypic and physiological responses of R. rotundifolia were investigated during three months of submergence, at water levels of 0 cm (CK), 50 cm (W50), and 90 cm (W90). Results showed that submergence stress reduced the relative growth rate of plant height, fresh weight, and biomass accumulation, leading to root degradation and a significant decline in the root-shoot ratio. The amounts of soluble protein (SP), soluble sugar (SS), and starch in the aerial leaves of W50 and W90 decreased during the early stages of submergence compared to CK, whereas the total chlorophyll and proline contents, and activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) increased. The contents of endogenous hormones, including abscisic acid (ABA), gibberellin (GA), and indole-3-acetic acid (IAA), decreased during the change in leaf shape; the decline in ABA was more obvious. The leaf primordium generated transition leaves and submerged leaves to resolve the "carbon starvation" of plants. The maximum values of non-structural carbohydrates (NSC) in the leaves of W50 and W90 occurred at day 30, reaching 14.0 mg g- 1and 10.5 mg g- 1, respectively. The contents of SP and starch, activities of SOD and CAT of the roots in submerged treatments increased, while SS and proline content decreased at day 7. These results demonstrated that developing heterophyllous leaves, increasing chlorophyll content, and regulating plant carbon allocation and consumption were important mechanisms of R. rotundifolia to adapt to underwater habitats.

The transcription factor Stat-1 is essential for Schwann cell differentiation, myelination and myelin sheath regeneration.

BACKGROUND: Myelin sheath is a crucial accessory to the functional nerve-fiber unit, its disruption or loss can lead to axonal degeneration and subsequent neurodegenerative diseases (NDs). Notwithstanding of substantial progress in possible molecular mechanisms underlying myelination, there is no therapeutics that prevent demyelination in NDs. Therefore, it is crucial to seek for potential intervention targets. Here, we focused on the transcriptional factor, signal transducer and activator of transcription 1 (Stat1), to explore its effects on myelination and its potential as a drug target. METHODS: By analyzing the transcriptome data obtained from Schwann cells (SCs) at different stages of myelination, it was found that Stat1 might be involved in myelination. To test this, we used the following experiments: (1) In vivo, the effect of Stat1 on remyelination was observed in an in vivo myelination mode with Stat1 knockdown in sciatic nerves or specific knockdown in SCs. (2) In vitro, the RNA interference combined with cell proliferation assay, scratch assay, SC aggregate sphere migration assay, and a SC differentiation model, were used to assess the effects of Stat1 on SC proliferation, migration and differentiation. Chromatin immunoprecipitation sequencing (ChIP-Seq), RNA-Seq, ChIP-qPCR and luciferase activity reporter assay were performed to investigate the possible mechanisms of Stat1 regulating myelination. RESULTS: Stat1 is important for myelination. Stat1 knockdown in nerve or in SCs reduces the axonal remyelination in the injured sciatic nerve of rats. Deletion of Stat1 in SCs blocks SC differentiation thereby inhibiting the myelination program. Stat1 interacts with the promoter of Rab11-family interacting protein 1 (Rab11fip1) to initiate SC differentiation. CONCLUSION: Our findings demonstrate that Stat1 regulates SC differentiation to control myelinogenic programs and repair, uncover a novel function of Stat1, providing a candidate molecule for clinical intervention in demyelinating diseases.

Constructing Carbon Nanotube-Enhanced Ultra-Thin Organic Compounds with Multi-Redox Sites for "All-Temperature" Potassium-Ion Battery Anode and its Step-Wise K-Storage Mechanism.

Organic compounds are regarded as important candidates for potassium-ion batteries (KIBs) due to their light elements, controllable polymerization, and tunable functional groups. However, intrinsic drawbacks largely restrict their application, including possible solubility in electrolytes, poor conductivity, and low diffusion coefficients. To address these issues, an ultrathin layered pyrazine/carbonyl-rich material (CT) is synthesized via an acid-catalyzed solvothermal reaction and homogeneously grown on carbon nanotubes (CNTs), marked as CT@CNT. Such materials have shown good features of exposing functional groups to guest ions and good electron transport paths, exhibiting high reversible capacity and remarkable rate capability over a wide temperature range. Two typical electrolytes are compared, demonstrating that the electrolyte of LX-146 is more suitable to maximize the electrochemical performances of electrodes at different temperatures. A stepwise reaction mechanism of K-chelating with C═O and C═N functional groups is proposed, verified by in/ex situ spectroscopic techniques and theoretical calculations, illustrating that pyrazines and carbonyls play the main roles in reacting with K+ cations, and CNTs promote conductivity and restrain electrode dissolution. This study provides new insights to understand the K-storage behaviors of organic compounds and their "all-temperature" application.

Preparation and SERS applications of Ta2O5 composite nanostructures.

Noble metal and semiconductor composite substrates possess high sensitivity, excellent stability, good biocompatibility, and selective enhancement, making them an important research direction in the field of surface-enhanced Raman scattering (SERS). Ta2O5, as a semiconductor material with high thermal stability, corrosion resistance, outstanding optical properties, and catalytic performance, has great potential in SERS research. This study aims to design and fabricate a composite SERS substrate based on Ta2O5 nanostructures, achieving optimal detection performance by combining the urchin-like structure of Ta2O5 with silver nanoparticles (Ag NPs). The urchin-like Ta2O5 nanostructures were prepared using a hydrothermal reaction method. The bandgap was modulated through structure design and the self-doping technique, the charge transfer efficiency and surface plasmon resonance effects were improved, thereby achieving better SERS performance. The composite substrate enables highly sensitive quantitative detection. This composite SERS substrate combines the electromagnetic enhancement mechanism (EM) and chemical enhancement mechanism (CM), achieving ultra-low detection limits of 10-13 M for R6G. Within the concentration range above 10-12 M, there is a good linear relationship between concentration and peak intensity, demonstrating excellent quantitative analysis capabilities. Furthermore, this composite SERS substrate is capable of precise detection of analytes such as crystal violet (CV) and methylene blue (MB), holding broad application prospects in areas such as food safety and environmental monitoring.

High-yield α-humulene production in Yarrowia lipolytica from waste cooking oil based on transcriptome analysis and metabolic engineering.

BACKGROUND: α-Humulene is an important biologically active sesquiterpene, whose heterologous production in microorganisms is a promising alternative biotechnological process to plant extraction and chemical synthesis. In addition, the reduction of production expenses is also an extremely critical factor in the sustainable and industrial production of α-humulene. In order to meet the requirements of industrialization, finding renewable substitute feedstocks such as low cost or waste substrates for terpenoids production remains an area of active research. RESULTS: In this study, we investigated the feasibility of peroxisome-engineering strain to utilize waste cooking oil (WCO) for high production of α-humulene while reducing the cost. Subsequently, transcriptome analysis revealed differences in gene expression levels with different carbon sources. The results showed that single or combination regulations of target genes identified by transcriptome were effective to enhance the α-humulene titer. Finally, the engineered strain could produce 5.9 g/L α-humulene in a 5-L bioreactor. CONCLUSION: To the best of our knowledge, this is the first report that converted WCO to α-humulene in peroxisome-engineering strain. These findings provide valuable insights into the high-level production of α-humulene in Y. lipolytica and its utilization in WCO bioconversion.

Pharmacokinetic study of deufruquintinibs in rats by HPLC-MS/MS after oral administration.

A sensitive and specific high-performance liquid chromatography-tandem mass spectrometry method was established to quantitatively determine the pharmacokinetics of fruquintinib (HMPL-013) and its derivatives [deufruquintinib-3D (HMPL-013-3D), deufruquintinib-6D (HMPL-013-6D) and deufruquintinib-9D (HMPL-013-9D)] in rats. Detection was performed on a triple quadrupole mass spectrometer in multiple reaction monitoring mode. The method established in this assay was successfully applied to a pharmacokinetic study of HMPL-013 and HMPL-013-Ds after oral administration. These results showed that HMPL-013-Ds had longer half-life and larger area under the plasma concentration-time curve than HMPL-013, especially HMPL-013-6D, which provides a significant basis for innovative ideas for drug structure transformation to reduce drug administration frequency and dosage.

Preparation of a superhydrophobic AgNP/GF substrate and its SERS application in a complex detection environment.

Surface-enhanced Raman scattering (SERS) is widely considered to be a fingerprint spectrum that can realize molecular identification, and it continues to receive a lot of attention due to its high sensitivity and powerful qualitative analysis capabilities. In recent years, there has been a lot of work and reports on super-sensitive SERS substrates, but often the enhanced ability of the substrate is also effective for impurities and irrelevant molecules. Therefore, a problem that still remains to be solved is how to perform effective trace detection of specific substances in a complex detection environment. Herein, a superhydrophobic Ag nanoparticle/glass microfibre filter (AgNP/GF) substrate was designed to realize the Raman detection of complex multiphase solutions. The hydrophobic three-dimensional net-like structure provides efficient Raman enhancement, making the substrate have extremely high detection limits for dye molecules and even achieving specific detection of the hexane phase component (thiram molecule) in a multiphase solution.

Preparation and surface-enhanced Raman scattering properties of GO/Ag/Ta2O5 composite substrates.

The composite substrate composed of precious metal, semiconductor and graphene has not only high sensitivity and uniform Raman signal but also stable chemical properties, which is one of the important topics in the field of surface-enhanced Raman scattering (SERS). In this paper, a sandwich SERS substrate based on tantalum oxide (Ta2O5) is designed and fabricated. The substrate has high sensitivity, stable performance and high quantification capability. The composite substrate can achieve a high sensitivity Raman detection of crystal violet (CV) with a detection limit of 10-11 M and an enhancement factor of 1.5 × 109. This is the result of the synergistic effect of electromagnetic enhancement and chemical enhancement, in which the chemical enhancement is the cooperative charge transfer in the system composed of probe molecules, silver nanoparticles (AgNPs) and Ta2O5, and the electromagnetic enhancement comes from the strong local surface plasmon resonance between the adjacent AgNPs. After exposing the composite substrate to the air for one month, the Raman signal did not weaken, indicating that the performance of the composite substrate is stable. In addition, there is an excellent linear relationship between the intensity of Raman characteristic peak and the concentration of probe molecules, which proves that the composite substrate has high quantification capability. In practical application, the composite SERS substrate can be used to detect harmful malachite green quickly and sensitively and has a broad application prospect in the field of food safety and chemical analysis.

SERS substrate with wettability difference for molecular self-concentrating detection.

The surface-enhanced Raman spectroscopy (SERS) has attracted much attention due to the powerful capability of quantificational analysis. Nowadays, most of the enhancement effect by SERS substrate is provided by the 'hot spots' occupying relatively small space. When the amount of analyte is too low, it is difficult to ensure that all the probe molecules can be placed into the 'hot spots', which is a headache in SERS quatification. In order to solve this problem, we have developed a structure of CuO nanowires/Ag nanoparticles with wettability capacity difference, which can aggregate molecules in water and oil simultaneously under two different mechanisms. The limit of detection and enhancement factor of this structure are estimated as 10-15M and 1.55 × 1011respectively (for rhodamine 6G, R6G). In a proof-in-principle experiment of sewage detection, it successfully achieved the aggregation and additional enhancement of both the R6G molecules in aqueous solution and thiuram molecules in toluene, realizing efficient and accurate Raman detection.

Heterostructured Cu2O-Au nanowire as a dual-functional nanocomposite for environmental pollutant degradation and hydrogen peroxide sensing.

Materials engineering is generally regarded as one of the most effective methods in the construction of photocatalysts, but it still faces many challenges. In this context, we designed and prepared a three-dimensional (3D) heterostructure of nanowires (NWs) formed by Cu2O core and an Au shell. The Cu2O-Au NWs not only show fine photocatalytic ability but also proved to have Fenton-like chemical properties and can be used as a hydrogen peroxide sensor. Moreover, this heterostructure realizes an integration of catalytic efficiency, retrievability, and versatility. In further consideration of the facile preparation process and low-cost material source of the structure, the Cu2O-Au NWs show a promising application prospect in the field of multifunctional photocatalysts.

Genome-wide association studies and CRISPR/Cas9-mediated gene editing identify regulatory variants influencing eyebrow thickness in humans.

Hair plays an important role in primates and is clearly subject to adaptive selection. While humans have lost most facial hair, eyebrows are a notable exception. Eyebrow thickness is heritable and widely believed to be subject to sexual selection. Nevertheless, few genomic studies have explored its genetic basis. Here, we performed a genome-wide scan for eyebrow thickness in 2961 Han Chinese. We identified two new loci of genome-wide significance, at 3q26.33 near SOX2 (rs1345417: P = 6.51×10(-10)) and at 5q13.2 near FOXD1 (rs12651896: P = 1.73×10(-8)). We further replicated our findings in the Uyghurs, a population from China characterized by East Asian-European admixture (N = 721), the CANDELA cohort from five Latin American countries (N = 2301), and the Rotterdam Study cohort of Dutch Europeans (N = 4411). A meta-analysis combining the full GWAS results from the three cohorts of full or partial Asian descent (Han Chinese, Uyghur and Latin Americans, N = 5983) highlighted a third signal of genome-wide significance at 2q12.3 (rs1866188: P = 5.81×10(-11)) near EDAR. We performed fine-mapping and prioritized four variants for further experimental verification. CRISPR/Cas9-mediated gene editing provided evidence that rs1345417 and rs12651896 affect the transcriptional activity of the nearby SOX2 and FOXD1 genes, which are both involved in hair development. Finally, suitable statistical analyses revealed that none of the associated variants showed clear signals of selection in any of the populations tested. Contrary to popular speculation, we found no evidence that eyebrow thickness is subject to strong selective pressure.

Endothelin-1 rs9296344 associates with the susceptibility of childhood primary nephrotic syndrome.

BACKGROUND: Recently, the rs5370 single nucleotide polymorphisms (SNPs) of Endothelin-1 (EDN1) showed association with the susceptibility of childhood primary nephrotic syndrome (CPNS). This study aims to investigate potential relationships between other EDN1 SNPs and CPNS. METHODS: Seven SNPs (rs5370, rs10478723, rs1476046, rs1800541, rs2070698, rs2071942, and rs9296344) of the EDN1 gene were genotyped in 579 CPNS patients and 586 age-matched healthy children. Then, we analyzed potential associations of the six SNPs with susceptibility of CPNS by using rs5370 as a conditional variant in a logistic regression model. SNP-SNP interaction analysis was performed to investigate the joint effects of the seven SNPs in the pathogenesis of CPNS. RESULTS: Independent with rs5370, only rs9296344 significantly associated (T vs C, odds ratio [OR] = 0.71, 95% confidence interval [CI] = 0.57-0.88, P = .001) with the susceptibility of CPNS. Meanwhile, no joint effect among the analyzed seven SNPs was discovered in this study. CONCLUSIONS: This study discovered that C allele of rs9296344 on EDN1 is a novel independent risk factor for CPNS.

Impact of the variations in potential glycosylation sites of the hemagglutinin of H9N2 influenza virus.

Variations in the potential glycosylation sites were observed in hemagglutinin (HA) sequences of H9N2 avian influenza virus isolated in China, deposited in the Influenza Virus Resource of NCBI before 2017, which showed a deleted glycosylation site at amino acid residue 218, and an introduced glycosylation site at amino acid residue 313. Based on the variations in the glycosylation sites at these amino acids, H9N2 avian influenza viruses could be divided into three categories. Firstly, most of the H9N2 influenza viruses were 218G+ viruses; less 313G+ viruses were isolated between 1997 and 2004. Secondly, the occurrence of the 218G+/313G+ viruses increased, while the 218G+/313G- viruses decreased from 2005 to 2012. Thirdly, from 2013 to 2016, the 218G-/313G+ viruses were predominant compared to the 218G+/313G+ viruses. Here, based on an F/98 virus backbone, a 218G+/313G- virus, two reassortment viruses were generated, and named rF/HA218G+/313G+ and rF/HA 218G+/313G-, respectively. HA protein migration demonstrated that the glycosylation sites at amino acid residues 313 and 218 were both functional. The absence of the glycosylation site at amino acid residue 218 and the presence of the glycosylation site at amino acid residue 313 increased antibody binding and moderately prevented the virus from escaping neutralization with homologous antisera. Additionally, compared to the F/98 virus (218G+/313G-), the viruses rF/HA218G+/313G+ or rF/HA218G-/313G+ showed significantly increased infectivity of MDCK cells, chicken embryo eggs, and trachea and lung tissue of SPF chickens, but did not display differences in airborne spread in chickens or infectivity of mice compared with its parental virus F/98.

Association of HLA-DQA1 gene polymorphisms with the risk of children primary nephrotic syndrome in Chinese population.

BACKGROUND: The association between gene polymorphisms and the risk of primary nephrotic syndrome (PNS) is uncovering recently. This study aims to investigate the relationship between single nucleotide polymorphisms (SNPs) on HLA-DQA1 gene and the risk of PNS. METHODS: In this study, we genotyped eight single nucleotide polymorphisms (SNPs) in the HLA-DQA1 gene in 501 PNS patients and 532 healthy people in Chinese population. Then we analyzed associations of these SNPs with the clinical features in primary nephrotic syndrome of children in Chinese population. RESULTS: Significant associations with PNS were found on missense SNP rs1129740 (GG vs AA, odds ratio (OR) = 1.987, 95% confidence interval (CI) = 1.468-2.652, P = 0.00177049) and rs1047992 (AA vs GG, OR = 1.857, 95% CI = 1.325-2.391, P = 1.1073E-10) of the HLA-DQA1 gene. CONCLUSIONS: This work suggests SNPs of HLA-DQA1 are risk factors for PNS in Chinese population, which implies roles of immune response in the pathogenesis of PNS.

Photosynthetic physiological performance and proteomic profiling of the oleaginous algae Scenedesmus acuminatus reveal the mechanism of lipid accumulation under low and high nitrogen supplies.

In this study, we presented cellular morphological changes, time-resolved biochemical composition, photosynthetic performance and proteomic profiling to capture the photosynthetic physiological response of Scenedesmus acuminatus under low nitrogen (3.6 mM NaNO3, N-) and high nitrogen supplies (18.0 mM NaNO3, N+). S. acuminatus cells showed extensive lipid accumulation (53.7% of dry weight) and were enriched in long-chain fatty acids (C16 & C18) under low nitrogen supply. The activity of PSII and photosynthetic rate decreases, whereas non-photochemical quenching and dark respiration rates were increased in the N- group. In addition, the results indicated a redistribution of light excitation energy between PSII and PSI in S. acuminatus exists before lipid accumulation. The iTRAQ results showed that, under high nitrogen supply, protein abundance of the chlorophyll biosynthesis, the Calvin cycle and ribosomal proteins decreased in S. acuminatus. In contrast, proteins associated with the photosynthetic machinery, except for F-type ATPase, were increased in the N+ group (N+, 3 vs. 9 days and 3 days, N+ vs. N-). Under low nitrogen supply, proteins involved in central carbon metabolism, fatty acid synthesis and branched-chain amino acid metabolism were increased, whereas the abundance of proteins of the photosynthetic machinery had decreased, with exception of PSI (N-, 3 vs. 9 days and 9 days, N+ vs. N-). Collectively, the current study has provided a basis for the metabolic engineering of S. acuminatus for biofuel production.

Duck Tembusu Virus Nonstructural Protein 1 Antagonizes IFN-ß Signaling Pathways by Targeting VISA.

Duck Tembusu virus (DTMUV) is an emergent infectious pathogen that has caused severe disease in ducks and huge economic losses to the poultry industry in China since 2009. Previously, we showed that DTMUV inhibits IFN-ß induction early in infection; however, the mechanisms of the inhibition of innate immune responses remain poorly understood. In this study, we screened DTMUV-encoded structural and nonstructural proteins using reporter assays and found that DTMUV NS1 markedly suppressed virus-triggered IFN-ß expression by inhibiting retinoic acid-inducible gene I-like receptor signaling. Moreover, we found that DTMUV NS1 specifically interacted with the C-terminal domain of virus-induced signaling adaptor and impaired the association of retinoic acid-inducible gene I or melanoma differentiation-associated gene 5 and virus-induced signaling adaptor, thereby downregulating the retinoic acid-inducible gene I-like receptor-mediated signal transduction and cellular antiviral responses, leading to evasion of the innate immune response. Together, our findings reveal a novel mechanism manipulated by DTMUV to circumvent the host antiviral immune response.