Nomograms established for predicting microvascular invasion and early recurrence in patients with small hepatocellular carcinoma.

BACKGROUND: In this study, we aimed to establish nomograms to predict the microvascular invasion (MVI) and early recurrence in patients with small hepatocellular carcinoma (SHCC), thereby guiding individualized treatment strategies for prognosis improvement. METHODS: This study retrospectively analyzed 326 SHCC patients who underwent radical resection at Wuhan Union Hospital between April 2017 and January 2022. They were randomly divided into a training set and a validation set at a 7:3 ratio. The preoperative nomogram for MVI was constructed based on univariate and multivariate logistic regression analysis, and the prognostic nomogram for early recurrence was constructed based on univariate and multivariate Cox regression analysis. We used the receiver operating characteristic (ROC) curves, area under the curves (AUCs), and calibration curves to estimate the predictive accuracy and discriminability of nomograms. Decision curve analysis (DCA) and Kaplan-Meier survival curves were employed to further confirm the clinical effectiveness of nomograms. RESULTS: The AUCs of the preoperative nomogram for MVI on the training set and validation set were 0.749 (95%CI: 0.684-0.813) and 0.856 (95%CI: 0.805-0.906), respectively. For the prognostic nomogram, the AUCs of 1-year and 2-year RFS respectively reached 0.839 (95%CI: 0.775-0.903) and 0.856 (95%CI: 0.806-0.905) in the training set, and 0.808 (95%CI: 0.719-0.896) and 0.874 (95%CI: 0.804-0.943) in the validation set. Subsequent calibration curves, DCA analysis and Kaplan-Meier survival curves demonstrated the high accuracy and efficacy of the nomograms for clinical application. CONCLUSIONS: The nomograms we constructed could effectively predict MVI and early recurrence in SHCC patients, providing a basis for clinical decision-making.

The meniscotibial ligament does exist: An anatomic and histological description.

Purpose: To describe the anatomical and histological characteristics of the human MTL (meniscotibial ligament) that keeps the meniscus stable and are rarely discussed. Study design: Descriptive laboratory study. Methods: In total, six fresh-frozen adult cadaver knees were dissected, and the dissection protocol were designed by two experienced anatomy professors. The anatomical morphology of MTL was observed. The main anatomical specimens included meniscus, tibial plateau, MTL. The osteotome was used to excise the portion of the tibial plateau, which could obtain the complex including partial meniscus, MTL, and a tibial fragment. A histopathologic study was performed by two experienced pathologists. Results: Macroscopically, the MTL could be divided into two parts: medial meniscotibial ligament (MMTL)and lateral meniscotibial ligament (LMTL). The MMTL is distributed continuously, whereas the LMTL is discontinuous on the tibial plateau. The average length from the tibial attachment of the LMTL to the articular surface was 19 ± 1.0mm (mean ± SD). The average length from the tibial attachment of the MMTL to the articular surface was 10 ± 1.2 mm (mean ± SD). Microscopy of the MTL showed that the MTL is a ligamentous tissue, composed of a network of oriented collagenous fibers. Conclusions: In all knees, the MTL was inserted on the outer edge of the meniscus, attaching to the tibia below the level of articular cartilage, which was key to maintaining the rotational stability of knee and the meniscus in the physiological position on the tibial plateau. Histological analysis of this ligament demonstrated that the MTL is a veritable ligamentous structure, which is made up of collagen type I-expressing fibroblasts. Clinical relevance: This article contributes to the understanding of the anatomical and histological characteristics of the MTL. It is beneficial to promote the development of relevant surgical techniques for the MTL lesion.

Holistic investigation of the anti-wrinkle and repair efficacy of a facial cream enriched with C-xyloside.

OBJECTIVE: To investigate the repairing and anti-wrinkle efficacy of the facial cream enriched with C-xyloside, aiming at comprehensively evaluating its skin anti- aging effect and clarify its potential mechanism of action. METHODS: The repairing efficacy was studied on 3D epidermis skin model and the antiaging efficacy was studied on ex-vivo human skin. Two clinical studies were conducted with Chinese females. In the first study, 49 subjects aged between 30 and 50 with wrinkle concerns were recruited and instructed to apply the investigational cream containing C-xyloside for 8 weeks. Wrinkles attributes were assessed by dermatologist. Instrumental measurements on skin hydration, trans-epidermal water loss (TEWL), and skin elasticity were also conducted. In the second study, 30 subjects aged between 25 and 60 with self-declared sensitive skin and facial redness were recruited and instructed to apply the cream for 4 weeks. Biomarker analysis of the stratum corneum was conducted through facial tape strips. RESULTS: The cream improved the histomorphology of the 3D epidermis skin model after SLS stimulation, and significantly increase the expression of LOR and FLG. On human skin, the cream improved the histopathology induced by UV, and significantly increased the protein content of COL I and COL III, collagen density and the number of Ki-67 positive cell of skin compared with model group (n = 3, p < 0.01). The results from the first clinical study demonstrate a significant increased the skin hydration and elasticity by 21.90%, 13.08% (R2) and 12.30% (R5), respectively (n = 49, p < 0.05), and the TEWL values decreased by 33.94% (n = 49, p < 0.05), after 8 weeks application of the cream. In addition, the scores for nasolabial folds, glabellar wrinkle, underneath eye wrinkles, crow's feet wrinkle and forehead wrinkle in the volunteers exhibited a significant reduction of 34.02%, 43.34%, 50.03%, 33.64% and 55.81% respectively (n = 49, p < 0.05). The (rCE)/(fCE) ratio of volunteers based on tape stripping significant increased after using the sample cream (n = 30, p < 0.05). CONCLUSION: The cream containing C-xyloside showed improvement of skin wrinkles and enhancement of skin barrier function. These efficacies may be attributed to the fact that the sample cream can increase the expression of skin barrier related proteins LOR and FLG, promote the maturation of cornified envelope, enhance collagen I and III protein expression and stimulate skin cell proliferation, to provide sufficient evidence supporting its antiaging efficacy of skin.

Advancing Superconductivity with Interface Engineering.

The development of superconducting materials has attracted significant attention not only for their improved performance, such as high transition temperature (TC), but also for the exploration of their underlying physical mechanisms. Recently, considerable efforts have been focused on interfaces of materials, a distinct category capable of inducing superconductivity at non-superconducting material interfaces or augmenting the TC at the interface between a superconducting material and a non-superconducting material. Here, two distinct types of interfaces along with their unique characteristics are reviewed: interfacial superconductivity and interface-enhanced superconductivity, with a focus on the crucial factors and potential mechanisms responsible for enhancing superconducting performance. A series of materials systems is discussed, encompassing both historical developments and recent progress from the perspectives of technical innovations and the exploration of new material classes. The overarching goal is to illuminate pathways toward achieving high TC, expanding the potential of superconducting parameters across interfaces, and propelling superconductivity research toward practical, high-temperature applications.

Organocatalytic Atroposelective Synthesis of Axially Chiral Indolyl Ketosulfoxonium Ylides.

Despite recent advancements in catalytic synthesis of axial chirality, reports on non-biaryl atropisomers remain limited because of the stringent steric requirements necessary to establish effective rotational brakes. In this study, we present a novel class of monoaryl atropisomers, indolyl ketosulfoxonium ylides, and describe an organocatalytic protocol for their synthesis. We discovered that a chiral phosphoric acid (CPA) serves as an effective catalyst for the highly enantioselective iodination of ortho-aminophenylethynyl sulfoxonium ylides. Under the optimized reaction conditions, a strong preference for the intended iodination process over the competing protonation was observed. Subsequently, intramolecular amide cyclization enabled the formation of sterically congested indole fragments. Furthermore, the synthetic utility of the products was demonstrated by showcasing versatile transformations into other chiral scaffolds with complete retention of optical purity.

Advancements in Non-Addictive Analgesic Diterpenoid Alkaloid Lappaconitine: A Review.

The perennial herb Aconitum sinomontanum Nakai (Ranunculaceae) has been utilized as a traditional oriental medicine in China for numerous years. The principal pharmacological constituent of A. sinomontanum, lappaconitine (LA), exhibits analgesic, anti-inflammatory, anti-tumor, anti-arrhythmic, and anti-epileptic activities. Due to its potent efficacy and non-addictive nature, LA is widely utilized in the management of cancer pain and postoperative analgesia. This review encompasses the research advancements pertaining to LA including extraction methods, separation techniques, pharmacological properties, chemical modifications, and clinical applications. Additionally, it offers insights into the potential applications and current challenges associated with LA to facilitate future research endeavors.

Employee perceived overqualification and innovation performance: the roles of self-oriented perfectionism and job crafting.

Leveraging the trait activation theory, the study constructs a model featuring moderated chain mediation to explore how perceived overqualification influences employee innovation performance. After conducting two surveys with Chinese employees, this study collects 363 valid questionnaires. The findings reveal that perceived overqualification is positively related to employee innovation performance. Both self-oriented perfectionism and job crafting are partial mediators between perceived overqualification and innovation performance, and they collectively play a chain mediating role. Furthermore, independent self-construction positively moderates the link between perceived overqualification and self-oriented perfectionism, and informal status positively moderates the relationship between job crafting and employee innovation performance. Additionally, the indirect influence of perceived overqualification on employee innovation performance is moderated by independent self-construction and informal status. This study adds to the current body of literature on perceived overqualification and offers practical implications for organizations aiming to enhance innovation performance.

Single-molecule sensing inside stereo- and regio-defined hetero-nanopores.

Heteromeric pore-forming proteins often contain recognition patterns or stereospecific selection filters. However, the construction of heteromeric pore-forming proteins for single-molecule sensing is challenging due to the uncontrollability of producing position isomers and difficulties in purification of regio-defined products. To overcome these preparation obstacles, we present an in situ strategy involving single-molecule chemical modification of a heptameric pore-forming protein to build a stereo- and regio-specific heteromeric nanopore (hetero-nanopore) with a subunit stoichiometric ratio of 3:4. The steric hindrance inherent in the homo-nanopore of K238C aerolysin directs the stereo- and regio-selective modification of maleimide derivatives. Our method utilizes real-time ionic current recording to facilitate controlled voltage manipulation for stoichiometric modification and position-based side-isomer removal. Single-molecule experiments and all-atom molecular dynamics simulations revealed that the hetero-nanopore features an asymmetric stereo- and regio-defined residue structure. The hetero-nanopore produced was characterized by mass spectrometry and single-particle cryogenic electron microscopy. In a proof-of-concept single-molecule sensing experiment, the hetero-nanopore exhibited 95% accuracy for label-free discrimination of four peptide stereoisomers with single-amino-acid structural and chiral differences in the mixtures. The customized hetero-nanopores could advance single-molecule sensing.

Feasibility study of a single-primer extension-based microhaplotype NGS system.

DNA degradation has been a thorny problem in forensic science. Shortening the amplicon length of the genetic markers improves the analysis of degraded DNA effectively. Microhaplotype (MH) has been proposed as a potential genetic marker that can be used for degraded DNA analysis. In the present study, a 146-plex MH-next-generation sequencing (NGS) system with an average Ae of 6.876 was constructed. Unlike other MH studies, a single-primer extension (SPE)-based NGS library preparation method was used to improve the detection of MH markers for degraded DNA. SPE employs a locus-specific and universal primer to amplify target fragments, reducing the necessity for complete fragment sequences. SPE might effectively mitigate the impact of degradation on amplification. However, SPE produces amplicons of varying lengths, posing challenges in allele calling for SPE-NGS data. To address this issue, this study proposed a flexible allele-calling strategy to improve amplicon detection. In addition, this study evaluated the forensic efficacy of the system using 12 low-template samples (from 1 ng to 7.8 pg), 10 mock-degraded DNA with various degrees of degradation, and 8 forensic casework samples. When the template is as low as 7.8 pg, our system can accurately detect at least 37 loci and achieves a random match probability (RMP) of 10-30 using the complete allele-calling strategy. Eighty-two loci can be detected, and RMP can reach 10-54 using a flexible allele-calling strategy. After 150 min of 98°C treatment, 36 loci can still be detected, and an RMP of 10-5 can be obtained using the flexible allele-calling strategy. Furthermore, the number of single nucleotide polymorphism detected at different DNA amounts and degradation levels suggests that the SPE method combined with a flexible allele-calling strategy is effective.

Bibliometric Analysis of Forensic Human Remains Identification Literature from 1991 to 2022.

OBJECTIVES: To describe the current state of research and future research hotspots through a metrological analysis of the literature in the field of forensic anthropological remains identification research. METHODS: The data retrieved and extracted from the Web of Science Core Collection (WoSCC), the core database of the Web of Science information service platform (hereinafter referred to as "WoS"), was used to analyze the trends and topic changes in research on forensic identification of human remains from 1991 to 2022. Network visualisation of publication trends, countries (regions), institutions, authors and topics related to the identification of remains in forensic anthropology was analysed using python 3.9.2 and Gephi 0.10. RESULTS: A total of 873 papers written in English in the field of forensic anthropological remains identification research were obtained. The journal with the largest number of publications was Forensic Science International (164 articles). The country (region) with the largest number of published papers was China (90 articles). Katholieke Univ Leuven (Netherlands, 21 articles) was the institution with the largest number of publications. Topic analysis revealed that the focus of forensic anthropological remains identification research was sex estimation and age estimation, and the most commonly studied remains were teeth. CONCLUSIONS: The volume of publications in the field of forensic anthropological remains identification research has a distinct phasing. However, the scope of both international and domestic collaborations remains limited. Traditionally, human remains identification has primarily relied on key areas such as the pelvis, skull, and teeth. Looking ahead, future research will likely focus on the more accurate and efficient identification of multiple skeletal remains through the use of machine learning and deep learning techniques.

Effect of Terminal Phosphate Groups on Collisional Dissociation of RNA Oligonucleotide Anions.

The increasing need for mass spectrometric analysis of RNA molecules calls for a better understanding of their gas-phase fragmentation behaviors. In this study, we investigate the effect of terminal phosphate groups on the fragmentation spectra of RNA oligonucleotides (oligos) using high-resolution mass spectrometry (MS). Negative-ion mode collision-induced dissociation (CID) and higher-energy collisional dissociation (HCD) were carried out on RNA oligos containing a terminal phosphate group on either end, both ends, or neither end. We find that terminal phosphate groups affect the fragmentation behavior of RNA oligos in a way that is dependent on the precursor charge state and the oligo length. Specifically, for precursor ions of RNA oligos of the same sequence, those with 5'- or 3'-phosphate, or both, have a higher charge state distribution and lose the phosphate group(s) in the form of a neutral (H3PO4 or HPO3) or an anion ([H2PO4]- or [PO3]-) upon CID or HCD. Such a neutral or charged loss is most conspicuous for precursor ions of an intermediate charge state, e.g., 3- for 4-nt oligos or 4- and 5- for 8-nt oligos. This decreases the intensity of sequencing ions (a-, a-B, b-, c-, d-, w-, x-, y-, z-ions) and hence is unfavorable for sequencing by CID or HCD. Removal of terminal phosphate groups by calf intestinal alkaline phosphatase improved MS analysis of RNA oligos. Additionally, the intensity of a fragment ion at m/z 158.925, which we identified as a dehydrated pyrophosphate anion ([HP2O6]-), is markedly increased by the presence of a terminal phosphate group. These findings expand the knowledge base necessary for software development for MS analysis of RNA.

Enhancing precision in effective regurgitant orifice area estimation by transthoracic echocardiography for functional mitral regurgitation using computational fluid dynamics.

Computational fluid dynamics (CFD) was used to identify factors influencing the accuracy of the hemispherical proximal isovelocity surface area (PISA) method in calculating the effective regurgitant orifice area (EROA) for patients with functional mitral regurgitation (FMR). Ninety-nine CFD models were constructed to investigate the impact of regurgitant orifice shape and leaflet tethering on the EROA calculation using the PISA method. The correction factors for regurgitation orifice shape (CFs) and for leaflet tethering (CFt) were derived by comparing the 2D PISA method and the actual orifice area. The correction formula was then tested in vivo via 2D transthoracic echocardiography with 3D transesophageal echocardiography of the vena contracta area (VCA) as a reference method in 62 patients with FMR. Based on the CFD simulation results, the two major factors for correcting the EROA calculation were vena contracta length (VCL) and coaptation depth (CD). The correction formula for the EROA was corrected effective regurgitant orifice area (CEROA) = EROA*CFs*CFt, where CFs = 0.59 × VCL(cm) + 0.6 × MR Vmax(cm/s)-0.63 × PISA R(cm)-1.51 and CFt = 0.4 × CD (cm) + 0.96. The correction formula was applied to FMR patients, and the bias and LOA between the CEROA and VCA (0.01 ± 0.13 cm2) were much smaller than those between the EROA and VCA (0.26 ± 0.32 cm2). The CFD-based correction formula improves the accuracy of the EROA calculation based on the hemispheric PISA method, possibly leading to more accurate and reliable data for treatment decision-making in FMR patients.

Gd-EOB-DTPA enhanced MRI nomogram model to differentiate hepatocellular carcinoma and focal nodular hyperplasia both showing iso- or hyperintensity in the hepatobiliary phase.

BACKGROUND: To develop and validate a nomogram model based on Gd-EOB-DTPA enhanced MRI for differentiation between hepatocellular carcinoma (HCC) and focal nodular hyperplasia (FNH) showing iso- or hyperintensity in the hepatobiliary phase (HBP). METHODS: A total of 75 patients with 49 HCCs and 26 FNHs randomly divided into a training cohort (n = 52: 34 HCC; 18 FNH) and an internal validation cohort (n = 23: 15 HCC; 8 FNH). A total of 37 patients (n = 37: 25 HCC; 12 FNH) acted as an external test cohort. The clinical and imaging characteristics between HCC and FNH groups in the training cohort were compared. The statistically significant parameters were included into the FAE software, and a multivariate logistic regression classifier was used to identify independent predictors and establish a nomogram model. Receiver operating characteristic (ROC) curves were used to evaluate the prediction ability of the model, while the calibration and decision curves were used for model validation. Subanalysis was used to compare qualitative and quantitative characteristics of patients with chronic hepatitis and cirrhosis between the HCC and FNH groups. RESULTS: In the training cohort, gender, age, enhancement rate in the arterial phase (AP), focal defects in uptake were significant predictors for HCC showing iso- or hyperintensity in the HBP. In the training cohort, area under the curve (AUC), sensitivity and specificity of the nomogram model were 0.989(95%CI: 0.967-1.000), 97.1% and 94.4%. In the internal validation cohort, the above three indicators were 0.917(95%CI: 0.782-1.000), 93.3% and 87.5%. In the external test cohort, the above three indicators were 0.960(95%CI: 0.905-1.000), 84.0% and 100.0%. The results of subanalysis showed that age was the independent predictor in the patients with chronic hepatitis and cirrhosis between HCC and FNH groups. CONCLUSIONS: Gd-EOB-DTPA enhanced MRI nomogram model may be useful for discriminating HCC and FNH showing iso- or hyperintensity in the HBP before surgery.

CBX7 promotes choroidal neovascularization by activating the HIF-1α/VEGF pathway in choroidal vascular endothelial cells.

Vascular endothelial growth factor (VEGF) signaling is crucial for choroidal neovascularization (CNV), a major pathological feature of neovascular age-related macular degeneration (nAMD). Gene transcription of VEGF is mainly regulated by hypoxia-inducible factor 1-alpha (HIF-1α). The chromobox (CBX) family polycomb protein (Pc) subgroup includes CBX2, CBX4, CBX6, CBX7, and CBX8. CBX4 enhances hypoxia-induced VEGF expression and angiogenesis in hepatocellular carcinoma (HCC) cells by increasing HIF-1α's transcriptional activity. The objective of the study was to examine the functions of members of the CBX family Pc subgroup in choroidal vascular endothelial cells (CVECs) during CNV. CBX4 and CBX7 expression was up-regulated in hypoxic human choroidal vascular endothelial cells (HCVECs). In HCVECs, CBX7 facilitated HIF-1α transcription and expression, while CBX4 did not. In HCVECs, CBX7 stimulated HIF-1α's nuclear translocation and transcriptional activity, which in turn stimulated VEGF transcription and expression. The CBX7/HIF-1α/VEGF pathway promoted the migration, proliferation, and tube formation of HCVECs. The CBX7/HIF-1α/VEGF pathway was up-regulated in CVECs and in the mouse model with laser-induced CNV. Mouse CNV was lessened by the blockade of CBX7 through the down-regulation of HIF-1α/VEGF. In conclusion, CBX7 enhanced pro-angiogenic behaviors of hypoxic CVECs by up-regulating the HIF-1α/VEGF pathway, which contributing to the formation of mouse laser-induced CNV.

The application of vibrational spectroscopy in forensic analysis of biological evidence.

Vibrational spectroscopy is a powerful analytical domain, within which Fourier transform infrared spectroscopy (FTIR) and Raman spectroscopy stand as exemplars, offering high chemical specificity and sensitivity. These methodologies have been instrumental in the characterization of chemical compounds for an extensive period. They are particularly adept at the identification and analysis of minute sample quantities. Both FTIR and Raman spectroscopy are proficient in elucidating small liquid samples and detecting nuanced molecular alterations. The application of chemometrics further augments their analytical prowess. Currently, these techniques are in the research phase within forensic medicine and have yet to be broadly implemented in examination and identification processes. Nonetheless, studies have indicated that a combined classification model utilizing FTIR and Raman spectroscopy yields exceptional results for the identification of biological fluid-related information and the determination of causes of death. The objective of this review is to delineate the current research trajectory and potential applications of these two vibrational spectroscopic techniques in the detection of body fluids and the ascertainment of causes of death within the context of forensic medicine.

Design, synthesis and bioevaluation of dual EGFR-PI3Kα inhibitors for potential treatment of NSCLC.

Aberrant activation or mutation of the EGFR-PI3K-Akt-mTOR signaling pathway has been implicated in a wide range of human cancers, especially non-small-cell lung cancer (NSCLC). Thus, dual inhibition of EGFR and PI3K has been investigated as a promising strategy to address acquired drug resistance resulting from the use of tyrosine kinase inhibitors. A series of dual EGFR/PI3Kα inhibitors was synthesized using pharmacophore hybridization of the third-generation EGFR inhibitor olmutinib and the PI3Kα selective inhibitor TAK-117. The optimal compound 30k showed potent kinase inhibitory activities with IC50 values of 3.6 and 30.0 nM against EGFRL858R/T790M and PI3Kα, respectively. Compound 30k exhibited a significant antiproliferative effect in NCI-H1975 cells with a higher selectivity profile than olmutinib. The potential antitumor mechanism, molecular binding modes, and in vitro metabolic stability of compound 30k were also clarified.

Alkyl effects on charge recombination in copper electrolyte-based dye-sensitized solar cells: Insights for targeted molecular design towards high performance.

Two quinoxaline dyes utilized in copper-electrolyte-based dye-sensitized solar cells (Cu-DSSCs) are theoretically investigated to analyze the impact of alkyl chains on dye performance. The investigation shows that ZS4, known for its record efficiency of up to 13.2 %, exhibits higher electron coupling and fewer binding sites for dye-[Cu(tmby)2]2+ interaction compared to ZS5. Contrary to common belief, alkyl chains are found to not only provide shielding but also hinder the interaction between dye and [Cu(tmby)2]2+ by influencing the optimal conformation of dyes, thereby impeding the charge recombination process. It is crucial to consider the influence of alkyl chains on dye conformation when discussing the relationship between dye structure and performance, rather than oversimplifying it as often done traditionally. Building on these findings, eight dyes are strategically designed by adjusting the position of the alkyl chain to further decrease charge recombination compared to ZS4. Theoretical evaluation of these dyes reveals that changing the alkyl chain on the nitrogen atom from 2-ethylhexyl (ZS4) to 1-hexylheptyl (D3-2) not only reduces the charge recombination rate but also enhances light harvesting ability. Therefore, D3-2 shows potential as a candidate for experimental synthesis of high-performance Cu-DSSCs with improved efficiency.

Rapid Fabrication of Antilunar Dust Aluminum Surface by Nanosecond Laser Etching.

Although a dust-repellent surface is desirable for lunar exploration missions, its fabrication process is complicated and time-consuming. Herein, we report a simple and fast method to fabricate a lunar dust-repellent surface by texturing on an Al substrate via nanosecond laser etching. The laser-induced photothermal effect can rapidly create hierarchical papillary structures on 25 × 25 mm Al substrates (within 30 s). Both atomic force microscopy (AFM) and in situ scanning electron microscopy (SEM) reveal that such structures enable a reduced contact area between the Al substrate and lunar dust and thus reduced adhesion. The reduced dust adhesion force of Al substrates facilitates improving their antidust performance. By optimizing processing parameters, the Al substrate etched with a laser scanning spacing of 80 µm exhibits a lower dust adhesion force (9.58 nN) due to the smallest contact area with dust. Accordingly, its static antilunar dust performance (dust coverage of 1.95%) is significantly improved compared to the pristine Al substrate (dust coverage of 12.98%). Besides, the accumulated dust on the laser-etched Al substrates with low surface adhesion force is easily cleaned up by flipping and gravity (the dust residual rates are less than 17%). The Al substrate with excellent antidust ability presents good potential for lunar exploration missions.

Electro-optically tunable optical delay on a lithium niobate photonic chip.

An approach for continuous tuning of on-chip optical delay with a microring resonator is proposed and demonstrated. By introducing an electro-optically tunable waveguide coupler, the bus waveguide to the resonance coupling can be effectively tuned from the under-coupling regime to the over-coupling regime. The optical delay is experimentally characterized by measuring the relative phase shift between lasers and shows a large dynamic range of delay from -600 to 600 ps and an efficient tuning of delay from -430 to -180 ps and from 40 to 240 ps by only a 5 V voltage.

DHPS-Mediated Hypusination Regulates METTL3 Self-m6A-Methylation Modification to Promote Melanoma Proliferation and the Development of Novel Inhibitors.

Discovering new treatments for melanoma will benefit human health. The mechanism by which deoxyhypusine synthase (DHPS) promotes melanoma development remains elucidated. Multi-omics studies have revealed that DHPS regulates m6A modification and maintains mRNA stability in melanoma cells. Mechanistically, DHPS activates the hypusination of eukaryotic translation initiation factor 5A (eIF5A) to assist METTL3 localizing on its mRNA for m6A modification, then promoting METTL3 expression. Structure-based design, synthesis, and activity screening yielded the hit compound GL-1 as a DHPS inhibitor. Notably, GL-1 directly inhibits DHPS binding to eIF5A, whereas GC-7 cannot. Based on the clarification of the mode of action of GL-1 on DHPS, it is found that GL-1 can promote the accumulation of intracellular Cu2+ to induce apoptosis, and antibody microarray analysis shows that GL-1 inhibits the expression of several cytokines. GL-1 shows promising antitumor activity with good bioavailability in a xenograft tumor model. These findings clarify the molecular mechanisms by which DHPS regulates melanoma proliferation and demonstrate the potential of GL-1 for clinical melanoma therapy.