Dense Amorphous Passivation Layer Formed on Aluminum Alloy Surfaces by Femtosecond Laser-Assisted Oxygen-Rich Doping.

Aluminum (Al) alloy surfaces are prone to serious corrosion in humid and salt-laden environments, which promotes the development of numerous protective approaches. Although the amorphous state is more conducive to improve corrosion resistance compared with the crystalline state, it still faces coating design problems like insufficient adhesive strength and flaking-off tendency. Here, we propose a strategy of femtosecond laser-assisted oxygen-rich doping to in situ create a dense high-quality passivation layer on Al alloy surfaces. With respect to the femtosecond laser processing in traditional air ambience, the material surface modifications within the oxygen-rich environment demonstrate some distinctiveness. For the ridge area of the laser ablation grooves, the oxidation surface is separated into two layers: the outer region presents a loose and porous appearance similar to the observations in the air ambience, while the inner region exhibits complete and homogeneous oxidation, especially associated with the continuous distribution of the amorphous substance, in sharp contrast to the nanoscale discrete amorphous formation in the air case. Simultaneously, the high degree of material oxidization with the amorphous phase is also developed on the wallside area of the groove valleys, which is much different from the incomplete oxidation in the air ambience. As a result, the measured corrosion current decreases by 49 times to a value of Icorr = 1.19 × 10-10 A/cm2 relative to the laser treatment in the air environment. Such a method offers the prospect for elevating the anticorrosion performance of metal surfaces.

A novel homozygous mutation in ACTL7A leads to male infertility.

Male infertility, a global public health problem, exhibits complex pathogenic causes and genetic factors deserve further discovery and study. We identified a novel homozygous missense mutation c.224A > C (p.D75A) in ACTL7A gene in two infertile brothers with teratozoospermia by whole-exome sequencing (WES). In vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) showed fertilization failure of the two affected couples. The three-dimensional (3D) models showed that a small section of α-helix transformed into random coil in the mutant ACTL7A protein and mutant amino acid lacked a hydrogen bond with Ser170 amino acid. Immunofluorescence revealed that ACTL7A protein was degraded in sperms of patients. Transmission electron microscopy (TEM) analysis of sperms from the infertile patients showed that the irregular perinuclear theca (PT) and acrosomal ultrastructural defects. Furthermore, ACTL7A mutation caused abnormal localization and reduced the expression of PLCZ1 in sperms of the patients, which may be the key reasons for the fertilization failure after ICSI. Our findings expand the spectrum of ACTL7A mutations and provide novel theoretical basis for genetic counseling.

Development of periodically concentric rings within microcavity upon femtosecond laser irradiation.

Understanding the formation mechanisms of the nanostructures and their designs has important implications for both the fundamental science and application prospects. In this study, we proposed a strategy for femtosecond laser-induced high regularity concentric rings within silicon microcavity. The morphology of the concentric rings can be flexibly modulated by the pre-fabricated structures and the laser parameters. The physics involved is deeply explored by the Finite-Difference-Time-Domain simulations, which reveals that the formation mechanism can be attributed to the near-field interference of the incident laser and the scattering light from the pre-fabricated structures. Our results provide a new method for creating the designable periodic surface structures.

Femtosecond laser upgrading the quality of bismuth films to enhance ultra-broadband photodetection.

Topological insulator bismuth has attracted considerable attention for the fabrication of room-temperature, wide bandwidth, and high-performance photodetectors due to the gapless edge state and insulating bulk state properties. However, both the photoelectric conversion and carrier transportation of the bismuth films are extremely affected by the surface morphology and grain boundaries to limit optoelectronic properties further. Here, we demonstrate a strategy of femtosecond laser treatment for upgrading the quality of bismuth films. After the treatment with proper laser parameters, the measurement of average surface roughness can be reduced from Ra = 44 nm to 6.9 nm, especially with accompany of the evident grain boundary elimination. Consequently, the photoresponsivity of the bismuth films increases approximately 2 times within an ultra-broad spectrum range from the visible to mid-infrared. This investigation suggests that the femtosecond laser treatment can help to benefit the performance of topological insulator ultra-broadband photodetectors.

Stabilization of SETD3 by deubiquitinase USP27 enhances cell proliferation and hepatocellular carcinoma progression.

The histone methyltransferase SETD3 plays critical roles in various biological events, and its dysregulation is often associated with human diseases including cancer. However, the underlying regulatory mechanism remains elusive. Here, we reported that ubiquitin-specific peptidase 27 (USP27) promotes tumor cell growth by specifically interacting with SETD3, negatively regulating its ubiquitination, and enhancing its stability. Inhibition of USP27 expression led to the downregulation of SETD3 protein level, the blockade of the cell proliferation and tumorigenesis of hepatocellular carcinoma (HCC) cells. In addition, we found that USP27 and SETD3 expression is positively correlated in HCC tissues. Notably, higher expression of USP27 and SETD3 predicts a worse survival in HCC patients. Collectively, these data elucidated that a USP27-dependent mechanism controls SETD3 protein levels and facilitates its oncogenic role in liver tumorigenesis.

Variation of Aroma Components of Pasteurized Yogurt with Different Process Combination before and after Aging by DHS/GC-O-MS.

Pasteurized yogurt is a healthy yogurt that can be stored in ambient temperature conditions. Dynamic headspace sampling (DHS) combined with gas chromatography-olfactory mass spectrometry (GC-O-MS), sensory evaluation, electronic nose (E-nose), and partial least squares discriminant analysis (PLS-DA) were used to analyze the flavor changes of pasteurized yogurt with different process combinations before and after aging. The results of odor profiles showed that the sensory descriptors of fermented, sweet, and sour were greatly affected by different process combinations. The results of odor-active compounds and relative odor activity value (r-OAV) showed that the combination of the production process affected the overall odor profile of pasteurized yogurt, which was consistent with the sensory evaluation results. A total of 15 odor-active compounds of 38 volatile compounds were detected in pasteurized yogurt samples. r-OAV results revealed that hexanal, (E)-2-octenal, 2-heptanone, and butanoic acid may be important odor-active compounds responsible for off-odor in aged, pasteurized yogurt samples. PLS-DA and variable importance of projection (VIP) results showed that butanoic acid, hexanal, acetoin, decanoic acid, 1-pentanol, 1-nonanal, and hexanoic acid were differential compounds that distinguish pasteurized yogurt before and after aging.

Two novel STAT1 mutations cause Mendelian susceptibility to mycobacterial disease.

Mendelian susceptibility to mycobacterial disease (MSMD) is a rare monogenetic disease, which is characterized by susceptibility to some weakly virulent mycobacteria. Here, we explored the pathogenic genes and molecular mechanisms of MSMD patients. We recruited three patients diagnosed with MSMD from two families. Two novel mutations (c.1228A > G, p.K410E and c.2071A > G, p.M691V) in STAT1 gene were identified from two families. The translocation of K410E mutant STAT1 protein into nucleus was not affected. The binding ability between gamma-activating sequence (GAS) and K410E mutant STAT1 protein was significantly reduced, which will reduce the interaction between STAT1 protein with the promoters of target genes. The M691V mutant STAT1 protein cannot translocate into the nucleus after IFN-γ stimulation, which will affect the STAT1 protein form gamma-activating factors (GAF) and bind the GAS in the promoter region of downstream target genes. Taken together, our results showed that the mutation of K410E led to impaired binding of STAT1 to target DNA, and the mutation of M691V prevented the transport of STAT1 into the nucleus, which led to MSMD. Together, we identified two novel mutations (c.1228A > G, p.K410E and c.2071A > G, p.M691V) in STAT1 gene in MSMD patients, and deciphered the molecular mechanism of MSMD caused by STAT1 mutations.

Effects of heterospecific pollen on stigma behavior in Campsis radicans: Causes and consequences.

PREMISE: Pollinator sharing of co-flowering plants may result in interspecific pollen receipt with a fitness cost. However, the underlying factors that determine the effects of heterospecific pollen (HP) are not fully understood. Moreover, the cost of stigma closure induced by HP may be more severe for plants with special touch-sensitive stigmas than for plants with non-touch-sensitive stigmas. Very few studies have assessed HP effects on stigma behavior. METHODS: We conducted hand-pollination experiments with 10 HP donors to estimate HP effects on stigma behavior and stigmatic pollen germination in Campsis radicans (Bignoniaceae) at low and high pollen loads. We assessed the role of phylogenetic distance between donor and recipient, pollen size, and pollen aperture number in mediating HP effects. Additionally, we observed pollen tube growth to determine the conspecific pollen-tube-growth advantage. RESULTS: Stigma behavior differed significantly with HP of different species. Pollen load increased, while pollen size decreased, the percentage of permanent closure and stigmatic germination of HP. Stigmatic HP germination increased with increasing aperture number. However, HP effects did not depend on phylogenetic distance. In addition, conspecific pollen had a pollen-tube-growth advantage over HP. CONCLUSIONS: Our results provide a good basis for understanding the stigma-pollen recognition process of plant taxa with touch-sensitive stigmas. We concluded that certain flowering traits drive the HP effects on the post-pollination period. To better understand the impact of pollinator sharing and interspecific pollen transfer on plant evolution, we highlight the importance of evaluating more factors that determine HP effects at the community level.

Synergetic PtNP@Co3O4 hollow nanopolyhedrals as peroxidase-like nanozymes for the dual-channel homogeneous biosensing of prostate-specific antigen.

In this paper, novel synergetic PtNP@Co3O4 hollow nanopolyhedrals with peroxidase-like activities are designed and prepared, which can be used as electrochemical and colorimetric signal labels for the enzyme-free dual-channel homogeneous sensing of prostate-specific antigen. When prostate-specific antigens are present, the aptamer-modified PtNP@Co3O4 hollow nanopolyhedrals and magnetic beads form sandwich structures, which have excellent peroxidase-like activities, because of the synergetic effect of PtNP@Co3O4 hollow nanopolyhedrals. The sandwich structures can be separated from the mixture by the magnetic effect of the magnetic beads and catalyze the redox reactions between H2O2 and TMB, generating quantitative electrochemical and colorimetric responses in homogeneous solution simultaneously. Under the optimized conditions, the linear range of both electrochemical (0.01 to 10 ng/ml) and colorimetric (0.01-15 ng/ml) channels can satisfy the demand of prostate-specific antigen detection in clinic (4 ng/ml), and the electrochemical and colorimetric channels have a low detection limit of 0.0079 ng/ml and 0.01 ng/ml respectively without using natural enzymes. The strategy by using synergetic PtNP@Co3O4 hollow nanopolyhedrals as signal probes provides a promising scheme for developing simple, rapid, reliable, and ultrasensitive dual-channel homogeneous biosensors, which has a great potential as a powerful tool in prostate cancer diagnosis.

Structural basis of N(6)-adenosine methylation by the METTL3-METTL14 complex.

Chemical modifications of RNA have essential roles in a vast range of cellular processes. N(6)-methyladenosine (m(6)A) is an abundant internal modification in messenger RNA and long non-coding RNA that can be dynamically added and removed by RNA methyltransferases (MTases) and demethylases, respectively. An MTase complex comprising methyltransferase-like 3 (METTL3) and methyltransferase-like 14 (METTL14) efficiently catalyses methyl group transfer. In contrast to the well-studied DNA MTase, the exact roles of these two RNA MTases in the complex remain to be elucidated. Here we report the crystal structures of the METTL3-METTL14 heterodimer with MTase domains in the ligand-free, S-adenosyl methionine (AdoMet)-bound and S-adenosyl homocysteine (AdoHcy)-bound states, with resolutions of 1.9, 1.71 and 1.61 Å, respectively. Both METTL3 and METTL14 adopt a class I MTase fold and they interact with each other via an extensive hydrogen bonding network, generating a positively charged groove. Notably, AdoMet was observed in only the METTL3 pocket and not in METTL14. Combined with biochemical analysis, these results suggest that in the m(6)A MTase complex, METTL3 primarily functions as the catalytic core, while METTL14 serves as an RNA-binding platform, reminiscent of the target recognition domain of DNA N(6)-adenine MTase. This structural information provides an important framework for the functional investigation of m(6)A.

Compound heterozygous variations in IARS1 cause recurrent liver failure and growth retardation in a Chinese patient: a case report.

BACKGROUND: Aminoacyl-tRNA synthetases (ARSs) are enzymes responsible for attaching amino acids to tRNA, which enables protein synthesis. Mutations in isoleucyl-tRNA synthetase (IARS1) have recently been reported to be a genetic cause for growth retardation, intellectual disability, muscular hypotonia, and infantile hepatopathy (GRIDHH). CASE PRESENTATION: In this study, we reported an additional case of compound heterozygous missense variations c.701 T > C (p.L234P) and c.1555C > T (p.R519C) in IARS1, which were identified using medical exome sequencing; c.701 T > C (p.L234P) was a novel variant, and c.1555C > T (p.R519C) was found in GnomAD. Unlike other reported patients, this individual presented prominently with recurrent liver failure, which led to her death at an early age of 19 months. She also had significant growth retardation, muscular hypotonia, chubby and flabby face, recurrent loose stools, and abnormal brain computed tomography (CT), while zinc deficiency and hearing loss were not present. Studies in zebrafish embryo modeling recapitulated some of the key phenotypic traits in embryo development, neurodevelopment, liver development, and myogenesis, demonstrating that these variations caused a loss of gene function in IARS1. CONCLUSIONS: We have found a novel mutation point c.701 T > C (p.L234P) in IARS1. Compound heterozygous mutations of c.701 T > C (p.L234P) and c.1555C > T (p.R519C) in IARS1 are pathogenic, which can cause GRIDHH in child.

Naphthalene Diimides Carrying Two ß-Cyclodextrins Prefer Telomere RNA G-Quadruplex Recognition.

Newly synthesized naphthalene diimide carrying two ß-cyclodextrins (NDI-ß-CyDs) showed improved specificity for the parallel G-quadruplex structure alongside the hybrid G-quadruplex structure. Specifically, the highest binding affinity of NDI-ß-CyDs for the telomere RNA G-quadruplex was observed. The binding simulation indicated that ß-cyclodextrins might be available for loop nucleobase inclusion under its complex.

Reduction of sodium chloride: a review.

Sodium chloride (NaCl) is an enjoyable condiment. However, evidence is accumulating to indicate that an excessive intake of Na+ in food may lead to an increased risk of cardiovascular and cerebrovascular diseases. Previous systematic reviews have focused on replacing NaCl with other metal salts (e.g. KCl). However, new salty flavor enhancers (yeast extract, taste peptides, and odor compounds) have yet to be reviewed. This systematic review evaluates the methods for, and feasibility, of NaCl reduction. It defines NaCl reduction and considers the methods used for this purpose, especially the use of flavor enhancers (yeast extract, taste peptides, and odor compounds). © 2022 Society of Chemical Industry.

pQLyCar: Peptide-based dynamic query-driven sample rescaling strategy for identifying carboxylation sites combined with KNN and SVM.

Lysine carboxylation is one of the most crucial type of post-translation modification, which plays a significant role in catalytic mechanisms. Therefore, it is essential to study lysine carboxylation and explore its biological mechanism. Compared with traditional experimental methods that are labor-intensive and time-consuming, computational methods are much more convenience and faster. Therefore, it is urgent to establish an accurate carboxylation identification model. Herein we proposed a method, named pQLyCar for identification of lysine carboxylation using SVM as classifier. In pQLyCar, a peptide-based dynamic query-driven sample rescaling strategy (pDQD-SR) is proposed to address the class imbalance of training data, which builds a specific prediction model for each query sample. KNN algorithm calculates distance between samples according to original sequences instead of feature vectors. Information entropy is applied to select optimal size of sliding window and various types of sequence- and position-based features are incorporated for construction of feature space, including residues composition (RC), K-space and position-special amino acid propensity (PSAAP). Finally, the performance of pQLyCar is measured with a specificity of 96.49% and a sensibility of 99.59% using jackknife test method, which indicated that pQLyCar method can be a useful tool for prediction of lysine carboxylation sites.

Grow fast but don't die young: Maternal effects mediate life-history trade-offs of lizards under climate warming.

As postulated by life-history theory, not all life-history traits can be maximized simultaneously. In ectothermic animals, climate warming is predicted to increase growth rates, but at a cost to overall life span. Maternal effects are expected to mediate this life-history trade-off, but such effects have not yet been explicitly elucidated. To understand maternal effects on the life-history responses to climate warming in lizard offspring, we conducted a manipulative field experiment on a desert-dwelling viviparous lacertid lizard Eremias multiocellata, using open-top chambers in a factorial design (maternal warm climate and maternal present climate treatments × offspring warm climate and offspring present climate treatments). We found that the maternal warm climate treatment had little impact on the physiological and life-history traits of adult females (i.e. metabolic rate, reproductive output, growth and survival). However, the offspring warm climate treatment significantly affected offspring growth, and both maternal and offspring warm climate treatments interacted to affect offspring survival. Offspring from the warm climate treatment grew faster than those from the present climate treatment. However, the offspring warm climate treatment significantly decreased the survival rate of offspring from maternal present climate treatment, but not for those from the maternal warm climate treatment. Our study demonstrates that maternal effects mediate the trade-off between growth and survival of offspring lizards, allowing them to grow fast without a concurrent cost of low survival rate (short life span). These findings stress the importance of adaptive maternal effects in buffering the impact of climate warming on organisms, which may help us to accurately predict the vulnerability of populations and species to future warming climates.

Substituent effects of cyclic naphthalene diimide on G-quadruplex binding and the inhibition of cancer cell growth.

Interaction of cyclic naphthalene diimide derivatives (cNDIs), 1-4, with TA-core and c-myc as G-quartet (G4) DNA was studied under dilute or molecular crowding condition. Binding study for TA-core based on an isothermal titration calorimetry showed that 1-4 has 106 M-1 order of binding affinity with the following order: 1 > 4 > 2 > 3 under both conditions. Meting temperature (Tm) of TA-core obtained from the temperature dependence of circular dichroism spectra shows that TA-core was most stabilized by 4, which is in agreement with the result of PCR stop assay and the stabilization effect for 1-3 was correlated with their binding affinity under dilute condition. 3 showed specific growth inhibition of cancer cell line Ca9-22 at <0.03 µM of IC50, with no inhibitory effect against normal bone marrow cells. 3, which has highest value of ΔH/ΔG, shows the highest inhibition ability for Ca9-22, carrying a highest expression level of telomerase mRNA.

Delineation of pentatricopeptide repeat codes for target RNA prediction.

Members of the pentatricopeptide repeat (PPR) protein family are sequence-specific RNA-binding proteins that play crucial roles in organelle RNA metabolism. Each PPR protein consists of a tandem array of PPR motifs, each of which aligns to one nucleotide of the RNA target. The di-residues in the PPR motif, which are referred to as the PPR codes, determine nucleotide specificity. Numerous PPR codes are distributed among the vast number of PPR motifs, but the correlation between PPR codes and RNA bases is poorly understood, which hinders target RNA prediction and functional investigation of PPR proteins. To address this issue, we developed a modular assembly method for high-throughput construction of designer PPRs, and by using this method, 62 designer PPR proteins containing various PPR codes were assembled. Then, the correlation between these PPR codes and RNA bases was systematically explored and delineated. Based on this correlation, the web server PPRCODE (http://yinlab.hzau.edu.cn/pprcode) was developed. Our study will not only serve as a platform for facilitating target RNA prediction and functional investigation of the large number of PPR family proteins but also provide an alternative strategy for the assembly of custom PPRs that can potentially be used for plant organelle RNA manipulation.

The Involvement of Ubiquitination Machinery in Cell Cycle Regulation and Cancer Progression.

The cell cycle is a collection of events by which cellular components such as genetic materials and cytoplasmic components are accurately divided into two daughter cells. The cell-cycle transition is primarily driven by the activation of cyclin-dependent kinases (CDKs), the activities of which are regulated by the ubiquitin-mediated proteolysis of key regulators such as cyclins and CDK inhibitors (CKIs). Thus, the ubiquitin-proteasome system (UPS) plays a pivotal role in the regulation of the cell-cycle process via recognition, interaction, and ubiquitination or deubiquitination of key proteins. The illegitimate degradation of tumor suppressor proteins and oncoproteins or, inversely, abnormally high accumulation results in cell proliferation deregulation, genomic instability, and cancer occurrence. In this review, we demonstrate the diversity and complexity of the UPS machinery regulation of the cell cycle. A profound understanding of the ubiquitination machinery will provide new insights into the regulation of the cell-cycle transition, cancer treatment, and the development of anti-cancer drugs.

The Roles of the Ubiquitin-Proteasome System in the Endoplasmic Reticulum Stress Pathway.

The endoplasmic reticulum (ER) is a highly dynamic organelle in eukaryotic cells, which is essential for synthesis, processing, sorting of protein and lipid metabolism. However, the cells activate a defense mechanism called endoplasmic reticulum stress (ER stress) response and initiate unfolded protein response (UPR) as the unfolded proteins exceed the folding capacity of the ER due to the environmental influences or increased protein synthesis. ER stress can mediate many cellular processes, including autophagy, apoptosis and senescence. The ubiquitin-proteasome system (UPS) is involved in the degradation of more than 80% of proteins in the cells. Today, increasing numbers of studies have shown that the two important components of UPS, E3 ubiquitin ligases and deubiquitinases (DUBs), are tightly related to ER stress. In this review, we summarized the regulation of the E3 ubiquitin ligases and DUBs in ER stress.

Cyclovirobuxine D Induced-Mitophagy through the p65/BNIP3/LC3 Axis Potentiates Its Apoptosis-Inducing Effects in Lung Cancer Cells.

Mitophagy plays a pro-survival or pro-death role that is cellular-context- and stress-condition-dependent. In this study, we revealed that cyclovirobuxine D (CVB-D), a natural compound derived from Buxus microphylla, was able to provoke mitophagy in lung cancer cells. CVB-D-induced mitophagy potentiates apoptosis by promoting mitochondrial dysfunction. Mechanistically, CVB-D initiates mitophagy by enhancing the expression of the mitophagy receptor BNIP3 and strengthening its interaction with LC3 to provoke mitophagy. Our results further showed that p65, a transcriptional suppressor of BNIP3, is downregulated upon CVB-D treatment. The ectopic expression of p65 inhibits BNIP3 expression, while its knockdown significantly abolishes its transcriptional repression on BNIP3 upon CVB-D treatment. Importantly, nude mice bearing subcutaneous xenograft tumors presented retarded growth upon CVB-D treatment. Overall, we demonstrated that CVB-D treatment can provoke mitophagy and further revealed that the p65/BNIP3/LC3 axis is one potential mechanism involved in CVB-D-induced mitophagy in lung cancer cells, thus providing an effective antitumor therapeutic strategy for the treatment of lung cancer patients.