Micropeptides: potential treatment strategies for cancer.

Some noncoding RNAs (ncRNAs) carry open reading frames (ORFs) that can be translated into micropeptides, although noncoding RNAs (ncRNAs) have been previously assumed to constitute a class of RNA transcripts without coding capacity. Furthermore, recent studies have revealed that ncRNA-derived micropeptides exhibit regulatory functions in the development of many tumours. Although some of these micropeptides inhibit tumour growth, others promote it. Understanding the role of ncRNA-encoded micropeptides in cancer poses new challenges for cancer research, but also offers promising prospects for cancer therapy. In this review, we summarize the types of ncRNAs that can encode micropeptides, highlighting recent technical developments that have made it easier to research micropeptides, such as ribosome analysis, mass spectrometry, bioinformatics methods, and CRISPR/Cas9. Furthermore, based on the distribution of micropeptides in different subcellular locations, we explain the biological functions of micropeptides in different human cancers and discuss their underestimated potential as diagnostic biomarkers and anticancer therapeutic targets in clinical applications, information that may contribute to the discovery and development of new micropeptide-based tools for early diagnosis and anticancer drug development.

Weakened tanning ability is an important mechanism for evolutionary skin lightening in East Asians.

The evolution of light-skin pigmentation among Eurasians is considered as an adaptation to the high-latitude environments. East Asians are ideal populations for studying skin color evolution because of the complex environment of East Asia. Here, we report a strong selection signal for the pigmentation gene phenylalanine hydroxylase (PAH) in light-skinned Han Chinese individuals. The intron mutation rs10778203 in PAH is enriched in East Asians and is significantly associated with skin color of the back of the hand in Han Chinese males (P < 0.05). In vitro luciferase and transcription factor binding assays show that the ancestral allele of rs10778203 could bind to SMAD2 and has a significant enhancer activity for PAH. However, the derived T allele (the major allele in East Asians) of rs10778203 decreases the binding activity of transcription factors and enhancer activity. Meanwhile, the derived T allele of rs10778203 shows a weaker ultraviolet radiation response in A375 cells and zebrafish embryos. Furthermore, rs10778203 decreases melanin production in transgenic zebrafish embryos after ultraviolet B (UVB) treatment. Collectively, PAH is a potential pigmentation gene that regulates skin tanning ability. Natural selection has enriched the adaptive allele, resulting in weakened tanning ability in East Asians, suggesting a unique genetic mechanism for evolutionary skin lightening in East Asians.

Tungsten Nitride with a Two-Dimensional Multilayer Structure for Boosting the Surface-Enhanced Raman Effect.

The development of high-performance surface-enhanced Raman scattering (SERS) substrates is an urgent and important task. Here, tungsten nitride (WN) with a two-dimensional (2D) multilayer structure has been successfully prepared through a nitriding WO2.90 precursor. In addition to the highly active "hot spots" formed on the surface of the WN sheets, a large number of gaps between the nanosheets also exhibit a strong local surface plasmon resonance effect, which greatly improves the SERS activity. Evaluated as the SERS substrate, the WN with a 2D multilayer structure exhibits good SERS characteristics and good homogeneity and stability, even after strong acid, strong alkali, or long-term light treatment. Significantly, typical environmental contaminants such as dichlorophenol and butylated hydroxyanisole also exhibit strong Raman enhancement signals. This research provides a new method for designing inexpensive, high-activity, and universal SERS substrates.

The Synthesis and Polymer-Reinforced Mechanical Properties of SiO2 Aerogels: A Review.

Silica aerogels are considered as the distinguished materials of the future due to their extremely low thermal conductivity, low density, and high surface area. They are widely used in construction engineering, aeronautical domains, environmental protection, heat storage, etc. However, their fragile mechanical properties are the bottleneck restricting the engineering application of silica aerogels. This review briefly introduces the synthesis of silica aerogels, including the processes of sol-gel chemistry, aging, and drying. The effects of different silicon sources on the mechanical properties of silica aerogels are summarized. Moreover, the reaction mechanism of the three stages is also described. Then, five types of polymers that are commonly used to enhance the mechanical properties of silica aerogels are listed, and the current research progress is introduced. Finally, the outlook and prospects of the silica aerogels are proposed, and this paper further summarizes the methods of different polymers to enhance silica aerogels.

Effect of Layered Aminovanadic Oxalate Phosphate on Flame Retardancy of Epoxy Resin.

To alleviate the fire hazard of epoxy resin (EP), layered ammonium vanadium oxalate-phosphate (AVOPh) with the structural formula of (NH4)2[VO(HPO4)]2(C2O4)·5H2O is synthesized using the hydrothermal method and mixed into an EP matrix to prepare EP/AVOPh composites. The thermogravimetric analysis (TGA) results show that AVOPh exhibits a similar thermal decomposition temperature to EP, which is suitable for flame retardancy for EP. The incorporation of AVOPh nanosheets greatly improves the thermal stability and residual yield of EP/AVOPh composites at high temperatures. The residue of pure EP is 15.3% at 700 °C. In comparison, the residue of EP/AVOPh composites is increased to 23.0% with 8 wt% AVOPh loading. Simultaneously, EP/6 wt% AVOPh composites reach UL-94 V1 rating (t1 + t2 =16 s) and LOI value of 32.8%. The improved flame retardancy of EP/ AVOPh composites is also proven by the cone calorimeter test (CCT). The results of CCT of EP/8 wt% AVOPh composites show that the peak heat release rate (PHHR), total smoke production (TSP), peak of CO production (PCOP), and peak of CO2 production (PCO2P) decrease by 32.7%, 20.4%, 37.1%, and 33.3% compared with those of EP, respectively. This can be attributed to the lamellar barrier, gas phase quenching effect of phosphorus-containing volatiles, the catalytic charring effect of transition metal vanadium, and the synergistic decomposition of oxalic acid structure and charring effect of phosphorus phase, which can insulate heat and inhibit smoke release. Based on the experimental data, AVOPh is expected to serve as a new high-efficiency flame retardant for EP.

The emerging role of exosomes in the development of testicular.

The mechanisms of testicular development in mammals are complex. Testis is an organ that produces sperm and secretes androgens. It is rich in exosomes and cytokines that mediate signal transduction between tubule germ cells and distal cells, promoting testicular development and spermatogenesis. Exosomes are nanoscale extracellular vesicles that transmit information between cells. By transmitting information, exosomes play an important role in male infertility diseases such as azoospermia, varicocele, and testicular torsion. However, due to the wide range of sources of exosomes, extraction methods are numerous and complex. Therefore, there are many difficulties in studying the mechanisms of exosomal effects on normal development and male infertility. Therefore, in this review, first, we introduce the formation of exosomes and methods for culturing testis and sperm. Then, we introduce the effects of exosomes on different stages of testicular development. Finally, we summarize the prospects and shortcomings of exosomes when used in clinical applications. We lay the theoretical foundation for the mechanism of the influence of exosomes on normal development and male infertility.

Amino Phenyl Copper Phosphate-Bridged Reactive Phosphaphenanthrene to Intensify Fire Safety of Epoxy Resins.

To improve the compatibility between flame retardant and epoxy resin (EP) matrix, amino phenyl copper phosphate-9, 10-dihydro-9-oxygen-10-phospha-phenanthrene-10-oxide (CuPPA-DOPO) is synthesized through surface grafting, which is blended with EP matrix to prepare EP/CuPPA-DOPO composites. The amorphous structure of CuPPA-DOPO is characterized by X-ray diffraction and Fourier-transform infrared spectroscopy. Scanning electron microscope (SEM) images indicate that the agglomeration of hybrids is improved, resisting the intense intermolecular attractions on account of the acting force between CuPPA and DOPO. The results of thermal analysis show that CuPPA-DOPO can promote the premature decomposition of EP and increase the residual amount of EP composites. It is worth mentioning that EP/6 wt% CuPPA-DOPO composites reach UL-94 V-1 level and limiting oxygen index (LOI) of 32.6%. Meanwhile, their peak heat release rate (PHRR), peak smoke production release (PSPR) and CO2 production (CO2P) are decreased by 52.5%, 26.1% and 41.4%, respectively, compared with those of EP. The inhibition effect of CuPPA-DOPO on the combustion of EP may be due to the release of phosphorus and ammonia free radicals, as well as the catalytic charring ability of metal oxides and phosphorus phases.

A double-edged sword: role of apoptosis repressor with caspase recruitment domain (ARC) in tumorigenesis and ischaemia/reperfusion (I/R) injury.

Apoptosis repressor with caspase recruitment domain (ARC) acts as a potent and multifunctional inhibitor of apoptosis, which is mainly expressed in postmitotic cells, including cardiomyocytes. ARC is special for its N-terminal caspase recruitment domain and caspase recruitment domain. Due to the powerful inhibition of apoptosis, ARC is mainly reported to act as a cardioprotective factor during ischaemia‒reperfusion (I/R) injury, preventing cardiomyocytes from being devastated by various catastrophes, including oxidative stress, calcium overload, and mitochondrial dysfunction in the circulatory system. However, recent studies have found that ARC also plays a potential regulatory role in tumorigenesis especially in colorectal cancer and renal cell carcinomas, through multiple apoptosis-associated pathways, which remains to be explored in further studies. Therefore, ARC regulates the body and maintains the balance of physiological activities with its interesting duplex. This review summarizes the current research progress of ARC in the field of tumorigenesis and ischaemia/reperfusion injury, to provide overall research status and new possibilities for researchers.

Improving the Thermal Stability and Flame Retardancy of Epoxy Resins by Lamellar Cobalt Potassium Pyrophosphate.

In order to improve the fire retardancy of epoxy resin (EP), lamellar cobalt potassium pyrophosphate (LCPP) nanocrystal whiskers with a length of 100-300 nm were designed and synthesized by a liquid technique. LCPP with high thermal stability was blended into EP to prepare the EP/LCPP composites. The results show that the EP/LCPP composites have higher thermal stability and produce more residues compared to pure EP. The combustion results display that the LOI value of the EP/10wt%LCPP composites was significantly improved to 35.9%, and the EP/6wt%LCPP composite can reach a UL-94 V-1 rating. Additionally, the peak heat release rate and peak smoke production rate of the EP/10wt%LCPP composites dramatically decreased by 43.8% and 48.5%, respectively. The improved flame retardancy and smoke suppression are mainly attributed to the inherent physical barrier of LCPP and the excellent catalytic carbonization ability of LCPP.

Genetic adaptation of skin pigmentation in highland Tibetans.

Strong ultraviolet (UV) radiation at high altitude imposes a serious selective pressure, which may induce skin pigmentation adaptation of indigenous populations. We conducted skin pigmentation phenotyping and genome-wide analysis of Tibetans in order to understand the underlying mechanism of adaptation to UV radiation. We observe that Tibetans have darker baseline skin color compared with lowland Han Chinese, as well as an improved tanning ability, suggesting a two-level adaptation to boost their melanin production. A genome-wide search for the responsible genes identifies GNPAT showing strong signals of positive selection in Tibetans. An enhancer mutation (rs75356281) located in GNPAT intron 2 is enriched in Tibetans (58%) but rare in other world populations (0 to 18%). The adaptive allele of rs75356281 is associated with darker skin in Tibetans and, under UVB treatment, it displays higher enhancer activities compared with the wild-type allele in in vitro luciferase assays. Transcriptome analyses of gene-edited cells clearly show that with UVB treatment, the adaptive variant of GNPAT promotes melanin synthesis, likely through the interactions of CAT and ACAA1 in peroxisomes with other pigmentation genes, and they act synergistically, leading to an improved tanning ability in Tibetans for UV protection.

Bufogarlides A-C, three new bufadienolides with Δ14,15 double bond from the skins of Bufo bufo gargarizans.

Three new bufadienolides with a Δ14,15 double bond, named bufogarlides A-C (1-3), together with three known analogs (4-6), were isolated from the skins of Bufo bufo gargarizans. Their structures were identified by analyses of spectroscopic data (1 D and 2 D NMR, HR-ESIMS), and comparison with the literature data. All the isolates were evaluated for their cytotoxic activities against ovarian carcinoma cell lines A2780 and SKOV3. Among them, compound 5 showed the highest potential for the growth inhibition of cancerous cells A2780 and SKOV3 with the IC50 values of 21.09 and 67.08 nM, respectively.

In Situ Surface Restraint-Induced Synthesis of Transition-Metal Nitride Ultrathin Nanocrystals as Ultrasensitive SERS Substrate with Ultrahigh Durability.

It is a major challenge to synthesize crystalline transition-metal nitride (TMN) ultrathin nanocrystals due to their harsh reaction conditions. Herein, we report that highly crystalline tungsten nitride (W2N, WN, W3N4, W2N3) nanocrystals with small size and excellent dispersibility are prepared by a mild and general in situ surface restraint-induced growth method. These ultrafine tungsten nitride nanocrystals are immobilized in ultrathin carbon layers, forming an interesting hybrid nanobelt structure. The hybrid WN/C nanobelts exhibit a strong localized surface plasmon resonance (LSPR) effect and surface-enhanced Raman scattering (SERS) effect, including a lowest detection limit of 1 × 10-12 M and a Raman enhancement factor of 6.5 × 108 comparable to noble metals, which may be one of the best records for non-noble metal SERS substrates. Moreover, they even can maintain the SERS performance in a variety of harsh environments, showing outstanding corrosion resistance, radiation resistance, and oxidation resistance, which is not available on traditional noble metal and semiconductor SERS substrates. A synergistic Raman enhancement mechanism of LSPR and interface charge transfer is found in the carbon-coated tungsten nitride substrate. A microfluidic SERS channel integrating the enrichment and detection of trace substances is constructed with the WN/C nanobelt, which realizes high-throughput dynamic SERS analysis.

Molybdenum Nitride Porous Prisms with a Strong Plasmon Resonance Effect in the Visible Region for Surface-Enhanced Raman Spectroscopy.

In surface-enhanced Raman spectroscopy (SERS) detection, the structure of the Raman-scattering substrate is critical to the sensitivity and stability of the detector. Herein, molybdenum nitride (MoN) porous structures with a well-defined hexagonal prism shape were synthesized via a precursor nitriding route. As a typical metallic transition-metal nitride (TMN), these molybdenum nitride porous hexagonal prisms exhibit a rare strong SPR effect in the visible region, with a resonance peak centered at 534 nm. Benefiting from the strong SPR effect and their huge surface area and porosity, these MoN porous hexagonal prisms exhibit surface-enhanced Raman scattering effects comparable to those of noble metals, with a Raman enhancement factor of 5.5 × 106. More importantly, these MoN SERS substrates exhibit ultrahigh chemical stabilities that noble metal and semiconductor substrates do not possess, which can prevent corrosion by strong acids, alkalis, and high-temperature oxidation.

Moving MoO2/C Nanospheres with the Functions of Enrichment and Sensing for Online-High-Throughput SERS Detection.

The development of online surface-enhanced Raman spectroscopy (SERS) detection methods is crucial to achieving high-throughput efficiency. Herein, a non-noble-metal moving substrate that integrates the functions of enrichment and sensing is developed for the microfluidic online-high-throughput detection of pollutants. The lowest limit of detection of 1 × 10-12 M and a Raman enhancement factor of 6.3 × 108 are obtained on the nanospheres. In a single detection channel, the analysis of 20 samples is achieved within 5 min, and the relative standard deviation of the signals is less than 6.8%. Compared with static SERS detection of fixed substrates, this dynamic SERS detection method greatly reduces the contamination memory effect of the analyte residue, enabling it to perform the sequential quantitative detection of samples with large concentration differences. Moreover, the current online SERS platform realizes the rapid quantitative detection of multicomponent samples.

Controllable Solid-Phase Fabrication of an Fe2O3/Fe5C2/Fe-N-C Electrocatalyst toward Optimizing the Oxygen Reduction Reaction in Zinc-Air Batteries.

Preparing advanced electrocatalysts via solid-phase reactions encounters the challenge of low controllability for multiconstituent hybridization and microstructure modulation. Herein, a hydrothermal-mimicking solid-phase system is established to fabricate novel Fe2O3/Fe5C2/Fe-N-C composites consisting of Fe2O3/Fe5C2 nanoparticles and Fe,N-doped carbon species with varying morphologies. The evolution mechanism featuring a competitive growth of different carbon sources in a closed hypoxic space is elucidated for a series of Fe2O3/Fe5C2/Fe-N-C composites. The size and dispersity of Fe2O3/Fe5C2 nanoparticles, the graphitization degree of the carbonaceous matrix, and their diverse hybridization states lead to disparate electrocatalytic behaviors for the oxygen reduction reaction (ORR). Among them, microspherical Fe2O3/Fe5C2/Fe-N-C-3 exhibits an optimal ORR performance and the as-assembled zinc-air battery shows all-round superiority to the Pt/C counterpart. This work presents a mild solid-phase fabrication technique for obtaining a variety of nanocomposites with effective control over composition hybridization and microstructural modulation, which is significantly important for the design and optimization of advanced electrocatalysts.

Identification of Pathologic and Prognostic Genes in Prostate Cancer Based on Database Mining.

Background: Prostate cancer (PCa) is an epithelial malignant tumor that occurs in the urinary system with high incidence and is the second most common cancer among men in the world. Thus, it is important to screen out potential key biomarkers for the pathogenesis and prognosis of PCa. The present study aimed to identify potential biomarkers to reveal the underlying molecular mechanisms. Methods: Differentially expressed genes (DEGs) between PCa tissues and matched normal tissues from The Cancer Genome Atlas Prostate Adenocarcinoma (TCGA-PRAD) dataset were screened out by R software. Weighted gene co-expression network analysis was performed primarily to identify statistically significant genes for clinical manifestations. Protein-protein interaction (PPI) network analysis and network screening were performed based on the STRING database in conjunction with Cytoscape software. Hub genes were then screened out by Cytoscape in conjunction with stepwise algorithm and multivariate Cox regression analysis to construct a risk model. Gene expression in different clinical manifestations and survival analysis correlated with the expression of hub genes were performed. Moreover, the protein expression of hub genes was validated by the Human Protein Atlas database. Results: A total of 1,621 DEGs (870 downregulated genes and 751 upregulated genes) were identified from the TCGA-PRAD dataset. Eight prognostic genes [BUB1, KIF2C, CCNA2, CDC20, CCNB2, PBK, RRM2, and CDC45] and four hub genes (BUB1, KIF2C, CDC20, and PBK) potentially correlated with the pathogenesis of PCa were identified. A prognostic model with good predictive power for survival was constructed and was validated by the dataset in GSE21032. The survival analysis demonstrated that the expression of RRM2 was statistically significant to the prognosis of PCa, indicating that RRM2 may potentially play an important role in the PCa progression. Conclusion: The present study implied that RRM2 was associated with prognosis and could be used as a potential therapeutic target for PCa clinical treatment.

Metformin induces S-adenosylmethionine restriction to extend the Caenorhabditis elegans healthspan through H3K4me3 modifiers.

Metformin, a widely prescribed first-line drug for the treatment of type II diabetes mellitus, has been shown to extend lifespan and delay the onset of age-related diseases. The precisely mechanisms by which these effects are realized remain elusive. We find that metformin exposure is restricted to adults, which is sufficient to extend lifespan. However, limiting metformin exposure to the larvae has no significant effect on Caenorhabditis elegans longevity. Here, we show that after metformin treatment, the level of S-adenosylmethionine (SAM) is reduced in adults but not in the larvae. Potential mechanisms by which reduced SAM might increase lifespan include altering the histone methylation. However, the molecular connections between metformin, SAM limitation, methyltransferases, and healthspan-associated phenotypes are unclear. Through genetic screening of C. elegans, we find that metformin promotes the healthspan through an H3K4 methyltransferase/demethylase complex to downregulate the targets, including mTOR and S6 kinase. Thus, our studies provide molecular links between meformin, SAM limitation, histone methylation, and healthspan and elucidate the mode action of metformin-regulated healthspan extension will boost its therapeutic application in the treatment of human aging and age-related diseases.

General Microwave Route to Single-Crystal Porous Transition Metal Nitrides for Highly Sensitive and Stable Raman Scattering Substrates.

The synthesis of metallic transition metal nitrides (TMNs) has traditionally been performed under harsh conditions, which makes it difficult to prepare TMNs with high surface area and porosity due to the grain sintering. Herein, we report a general and rapid (30 s) microwave synthesis method for preparing TMNs with high specific surface area (122.6-141.7 m2 g-1) and porosity (0.29-0.34 cm3 g-1). Novel single-crystal porous WN, Mo2N, and V2N are first prepared by this method, which exhibits strong surface plasmon resonance, photothermal conversion, and surface-enhanced Raman scattering effects. Different from the conventional low-temperature microwave absorbing media such as water and polymers, as new concept absorbing media, hydrated metal oxides and metallic metal oxides are found to have a remarkable high-temperature microwave heating effect and play key roles in the formation of TMNs. The current research results provide a new-concept microwave method for preparing high lattice energy compounds with high specific surface.

Selective Preparation of Mo2N and MoN with High Surface Area for Flexible SERS Sensing.

γ-Mo2N and δ-MoN are the two most important molybdenum nitrides, but controllable preparation of them with high surface area has not been achieved. Herein, we achieved selective preparation of γ-Mo2N and δ-MoN. The key factor for the selective preparation of γ-Mo2N and δ-MoN is to control the crystal phase of the precursor MoO3. In H2O and NH3 mixed gas, the α-MoO3 nanoribbons are nitridated to obtain γ-Mo2N single-crystal porous nanobelts, while the h-MoO3 prisms are nitrided to obtain δ-MoN hierarchical porous columns. The corrosion effect of H2O plays a key role in the formation of single-crystal porous structure. The γ-Mo2N flexible membrane composed of the single-crystal porous nanobelts exhibits strong localized surface plasmon resonance and surface enhanced Raman scattering effect, which show highly sensitive response to polychlorinated phenol.

Vanadium dioxide nanostructures with remarkable surface-enhanced Raman scattering activity.

Structure and size control are always considered to be effective routes to enhance the sensitivity of materials. Herein, rough VO2 (D) nanostars and nanospheres with highly dense and rough surfaces were synthesized. Accompanied by the properties inherited from the rough VO2 nanospheres, i.e., high adsorption and strong plasma resonance, these VO2 (D) nanospheres exhibit highly sensitive activity as a surface enhanced Raman spectrum substrate. The detection limit of Rhodamine 6G on this semiconductor SERS substrate is as low as 10-9 M.