Heterologous survey of 130 DNA transposons in human cells highlights their functional divergence and expands the genome engineering toolbox.

Experimental studies on DNA transposable elements (TEs) have been limited in scale, leading to a lack of understanding of the factors influencing transposition activity, evolutionary dynamics, and application potential as genome engineering tools. We predicted 130 active DNA TEs from 102 metazoan genomes and evaluated their activity in human cells. We identified 40 active (integration-competent) TEs, surpassing the cumulative number (20) of TEs found previously. With this unified comparative data, we found that the Tc1/mariner superfamily exhibits elevated activity, potentially explaining their pervasive horizontal transfers. Further functional characterization of TEs revealed additional divergence in features such as insertion bias. Remarkably, in CAR-T therapy for hematological and solid tumors, Mariner2_AG (MAG), the most active DNA TE identified, largely outperformed two widely used vectors, the lentiviral vector and the TE-based vector SB100X. Overall, this study highlights the varied transposition features and evolutionary dynamics of DNA TEs and increases the TE toolbox diversity.

Structural basis of ketamine action on human NMDA receptors.

Ketamine is a non-competitive channel blocker of N-methyl-D-aspartate (NMDA) receptors1. A single sub-anaesthetic dose of ketamine produces rapid (within hours) and long-lasting antidepressant effects in patients who are resistant to other antidepressants2,3. Ketamine is a racemic mixture of S- and R-ketamine enantiomers, with S-ketamine isomer being the more active antidepressant4. Here we describe the cryo-electron microscope structures of human GluN1-GluN2A and GluN1-GluN2B NMDA receptors in complex with S-ketamine, glycine and glutamate. Both electron density maps uncovered the binding pocket for S-ketamine in the central vestibule between the channel gate and selectivity filter. Molecular dynamics simulation showed that S-ketamine moves between two distinct locations within the binding pocket. Two amino acids-leucine 642 on GluN2A (homologous to leucine 643 on GluN2B) and asparagine 616 on GluN1-were identified as key residues that form hydrophobic and hydrogen-bond interactions with ketamine, and mutations at these residues reduced the potency of ketamine in blocking NMDA receptor channel activity. These findings show structurally how ketamine binds to and acts on human NMDA receptors, and pave the way for the future development of ketamine-based antidepressants.

Mechano-regulation of Peptide-MHC Class I Conformations Determines TCR Antigen Recognition.

TCRs recognize cognate pMHCs to initiate T cell signaling and adaptive immunity. Mechanical force strengthens TCR-pMHC interactions to elicit agonist-specific catch bonds to trigger TCR signaling, but the underlying dynamic structural mechanism is unclear. We combined steered molecular dynamics (SMD) simulation, single-molecule biophysical approaches, and functional assays to collectively demonstrate that mechanical force induces conformational changes in pMHCs to enhance pre-existing contacts and activates new interactions at the TCR-pMHC binding interface to resist bond dissociation under force, resulting in TCR-pMHC catch bonds and T cell activation. Intriguingly, cancer-associated somatic mutations in HLA-A2 that may restrict these conformational changes suppressed TCR-pMHC catch bonds. Structural analysis also indicated that HLA polymorphism might alter the equilibrium of these conformational changes. Our findings not only reveal critical roles of force-induced conformational changes in pMHCs for activating TCR-pMHC catch bonds but also have implications for T cell-based immunotherapy.

Transcriptome-based molecular subtypes and differentiation hierarchies improve the classification framework of acute myeloid leukemia.

The current classification of acute myeloid leukemia (AML) relies largely on genomic alterations. Robust identification of clinically and biologically relevant molecular subtypes from nongenomic high-throughput sequencing data remains challenging. We established the largest multicenter AML cohort (n = 655) in China, with all patients subjected to RNA sequencing (RNA-Seq) and 619 (94.5%) to targeted or whole-exome sequencing (TES/WES). Based on an enhanced consensus clustering, eight stable gene expression subgroups (G1-G8) with unique clinical and biological significance were identified, including two unreported (G5 and G8) and three redefined ones (G4, G6, and G7). Apart from four well-known low-risk subgroups including PML::RARA (G1), CBFB::MYH11 (G2), RUNX1::RUNX1T1 (G3), biallelic CEBPA mutations or -like (G4), four meta-subgroups with poor outcomes were recognized. The G5 (myelodysplasia-related/-like) subgroup enriched clinical, cytogenetic and genetic features mimicking secondary AML, and hotspot mutations of IKZF1 (p.N159S) (n = 7). In contrast, most NPM1 mutations and KMT2A and NUP98 fusions clustered into G6-G8, showing high expression of HOXA/B genes and diverse differentiation stages, from hematopoietic stem/progenitor cell down to monocyte, namely HOX-primitive (G7), HOX-mixed (G8), and HOX-committed (G6). Through constructing prediction models, the eight gene expression subgroups could be reproduced in the Cancer Genome Atlas (TCGA) and Beat AML cohorts. Each subgroup was associated with distinct prognosis and drug sensitivities, supporting the clinical applicability of this transcriptome-based classification of AML. These molecular subgroups illuminate the complex molecular network of AML, which may promote systematic studies of disease pathogenesis and foster the screening of targeted agents based on omics.

METTL3-mediated upregulation of FAM135B promotes EMT of esophageal squamous cell carcinoma via regulating the Wnt/ß-catenin pathway.

Family with sequence similarity 135 member B (FAM135B) is a novel driver gene in esophageal squamous cell carcinoma (ESCC). However, little is known regarding its biological functions and mechanisms in ESCC. Here, we identified that the high expression of FAM135B was associated with lymph node metastasis and infiltrating development of ESCC. Elevated FAM135B expression promoted ESCC migration and invasion in vitro and lung metastasis in vivo. Furthermore, epithelial-mesenchymal transition (EMT)-related pathways were enriched in ESCC samples with high levels of FAM135B and FAM135B positively regulated EMT markers. Mechanistically, we observed that FAM135B interacted with the intermediate domain of TRAF2 and NCK-interacting kinase (TNIK), activating the Wnt/ß-catenin signaling pathway. The facilitation of TNIK on ESCC migration and invasion was reversed by FAM135B siRNA. In addition, the N6-methyladenosine (m6A) modification positively regulated FAM135B expression, with methyltransferase like 3 (METTL3) acting as its substantial m6A writer. The pro-EMT effects of METTL3 overexpression were reversed by silencing FAM135B. Collectively, these findings illustrate the critical role of ABCDE in ESCC progression and provide new insights into the upstream and downstream mechanisms of FAM135B.NEW & NOTEWORTHY This study reveals for the first time that the novel cancer-related gene, FAM135B, promotes ESCC metastasis both in vitro and in vivo. Besides, we substantiate FAM135B's action on the ß-catenin pathway through interacting with TNIK, thereby elucidating the promotional effect of FAM135B on ESCC EMT. Furthermore, we provide initial evidence demonstrating that METTL3-mediated m6A modification upregulates the expression of FAM135B in ESCC cells.

Cuproptosis associated cytoskeletal destruction contributes to podocyte injury in chronic kidney disease.

The podocyte cytoskeleton determines the stability of podocyte structure and function, and their imbalance plays a pathogenic role in podocyte diseases. However, the underlying mechanism of podocyte cytoskeleton damage is not fully understood. Here, we investigate the specific role of cuproptosis in inducing podocyte cytoskeleton injury. In in vitro and in vivo studies, exposure to high levels of copper and adriamycin (ADR) caused significant increases in copper concentration in intracellular and renal tissue. Moreover, excessive accumulation of copper induced cuproptosis, resulting in the destruction of the podocyte cytoskeleton. However, inhibition of copper accumulation to reduce cuproptosis also significantly alleviated the damage of podocyte cytoskeleton. In addition, inhibition of cuproptosis mitigated ADR-induced mitochondrial damage as well as the production of reactive oxygen species and depolarization of mitochondrial membrane potential, and restored adenosine triphosphate (ATP) synthesis. Among the transcriptome sequencing data, the difference of CXCL5 (C-X-C motif chemokine ligand 5) was the most significant. Both high copper and ADR exposure can cause upregulation of CXCL5, and CXCL5 deletion inhibits the occurrence of cuproptosis, thereby alleviating the podocyte cytoskeleton damage. This suggests that CXCL5 may act upstream of cuproptosis that mediates podocyte cytoskeleton damage. In conclusion, cuproptosis induced by excessive copper accumulation may induce podocyte cytoskeleton damage by promoting mitochondrial dysfunction, thereby causing podocyte injury. This indicates that cuproptosis plays an important role in the pathogenesis of podocyte injury and provides a basis for seeking potential targets for the treatment of chronic kidney disease.NEW & NOTEWORTHY Cuproptosis induced by excessive copper accumulation leads to podocyte cytoskeleton damage by promoting mitochondrial dysfunction, and CXCL5 acts as an upstream signal mediating the occurrence of cuproptosis.

NLRP2 in health and disease.

NLR family pyrin domain containing 2 (NLRP2) is a novel member of the Nod-like receptor (NLR) family. However, our understanding of NLRP2 has long been ambiguous. NLRP2 may have a role in the innate immune response, but its 'specific' functions remain controversial. Although NLRP2 can initiate inflammasome and promote inflammation, it can also downregulate inflammatory signals. Additionally, NLRP2 has been reported to function in the reproductive system and shows high expression in the placenta. However, the exact role of NLRP2 in the reproductive system is unclear. Here, we highlight the most current progress on NLRP2 in inflammasome activation, effector function and regulation of nuclear factor-κB. And we discuss functions of NLRP2 in inflammatory diseases, reproductive disorders and the potential implication of NLRP2 in human diseases.

Resveratrol mediated the proliferation and apoptosis of gastric cancer cells by modulating the PI3K/Akt/P53 signaling pathway.

The aim of this study was to investigate the anti-cancer effects of resveratrol (RES) against gastric cancer (GC) and explore the potential mechanisms. We first measured the anti-cancer effects of RES on GC cell lines (i.e. AGS and HGC-27). Then protein-protein interaction (PPI) network was constructed, followed by GO and KEGG analysis to screen the possible targets. Molecular docking analysis was given to visualize the pharmacological effects of RES on GC cell lines. For the in vivo experiments, xenograft tumor model was established, and Western blot analysis was performed to determine the expression of protein screened by network pharmacology. Our results showed that RES could promote the apoptosis of GC cells. Five hub targets were identified by network pharmacology, including AKT1, TP53, JUN, ESR1 and MAPK14. GO and KEGG analyses revealed the PI3K/Akt/P53 signaling pathway was the most related signaling pathway. Molecular docking analysis indicated that RES could form 3 hydrogen bonds with AKT1 and 3 hydrogen bonds with TP53. The inhibitory effects of RES on the proliferation and promoting effects of RES on the apoptosis of AGS and HGC-27 cells were significantly reversed when blocking the PI3K-Akt signaling pathway using the LY294002. In vivo results showed that RES induced significant decrease of tumor volume and tumor weight without changing the body weight, or inducing significant cytotoxicities. Western blot analysis proved that RES could induce down-regulation of p-Akt and up-regulation of P53 in vivo. In conclusion, RES showed anti-cancer effects in GC by regulating the PI3K/Akt/P53 signaling pathway.

Electrochemical/Electrochemiluminescence Sensors Based on Vertically-Ordered Mesoporous Silica Films for Biomedical Analytical Applications.

Vertically-ordered mesoporous silica films (VMSF, also named as silica isoporous membranes) have shown tremendous potential in the field of electroanalytical sensors due to their unique features in terms of controllable and ultrasmall nanopores, high molecular selectivity and permeability, and mechanical stability. This review will present the recent progress on the biomedical analytical applications of VMSF, focusing on the small biomolecules, diseases-related biomarkers, drugs and cancer cells. Finally, conclusions with recent developments and future perspective of VMSF in the relevant fields will be envisioned.

Hexavalent Chromium Induces Neurotoxicity by Triggering Mitochondrial Dysfunction and ROS-Mediated Signals.

Hexavalent chromium (Cr (VI)), one of the most detrimental pollutants, has been ubiquitously present in the environment and causes serious toxicity to humans, such as hepatotoxicity, nephrotoxicity, pulmonary toxicity, and cardiotoxicity. However, Cr (VI)-induced neurotoxicity in primary neuron level has not been well explored yet. Herein, potassium dichromate (K2Cr2O7) was employed to examine the neurotoxicity of Cr (VI) in rat primary hippocampal neurons. MTT test was used to examine the neural viability. Mitochondrial dysfunction was assessed by the JC-1 probe and Mito-Tracker probe. DCFH-DA and Mito-SOX Red were utilized to evaluate the oxidative status. Bcl-2 family and MAPKs expression were investigated using Western blotting. The results demonstrated that Cr (VI) treatment dose- and time-dependently inhibited neural viability. Mechanism investigation found that Cr (VI) treatment causes mitochondrial dysfunction by affecting Bcl-2 family expression. Moreover, Cr (VI) treatment also induces intracellular reactive oxygen species (ROS) generation, DNA damage, and MAPKs activation in neurons. However, inhibition of ROS by glutathione (GSH) effectually balanced Bcl-2 family expression, attenuated DNA damage and the MAPKs activation, and eventually improved neural viability neurons. Collectively, these above results above suggest that Cr (VI) causes significant neurotoxicity by triggering mitochondrial dysfunction, ROS-mediated oxidative damage and MAKPs activation.

Amino Functionality Enables Aqueous Synthesis of Carboxylic Acid-Based MOFs at Room Temperature by Biomimetic Crystallization.

Enzyme immobilization within metal-organic frameworks (MOFs) is a promising solution to avoid denaturation and thereby utilize the desirable properties of enzymes outside of their native environments. The biomimetic mineralization strategy employs biomacromolecules as nucleation agents to promote the crystallization of MOFs in water at room temperature, thus overcoming pore size limitations presented by traditional postassembly encapsulation. Most biomimetic crystallization studies reported to date have employed zeolitic imidazole frameworks (ZIFs). Herein, we expand the library of MOFs suitable for biomimetic mineralization to include zinc(II) MOFs incorporating functionalized terephthalic acid linkers and study the catalytic performance of the enzyme@MOFs. Amine functionalization of terephthalic acids is shown to accelerate the formation of crystalline MOFs enabling new enzyme@MOFs to be synthesized. The structure and morphology of the enzyme@MOFs were characterized by PXRD, FTIR, and SEM-EDX, and the catalytic potential was evaluated. Increasing the linker length while retaining the amino moiety gave rise to a family of linkers; however, MOFs generated with the 2,2'-aminoterephthalic acid linker displayed the best catalytic performance. Our data also illustrate that the pH of the reaction mixture affects the crystal structure of the MOF and that this structural transformation impacts the catalytic performance of the enzyme@MOF.

Lathyrane and premyrsinane Euphorbia diterpenes against Alzheimer's disease: Bioinspired synthesis, anti-cholinesterase and neuroprotection bioactivity.

The first systematic acylated diversification of naturally scarce premyrsinane diterpenes, together with their biosynthetic precursors lathyrane diterpene were carried out. Two new series of premyrsinane derivates (1a-32a) and lathyrane derivates (1-32) were synthesized from the naturally abundant lathyrane diterpene Euphorbia factor L3 through a bioinspired approach. The cholinesterase inhibitory and neuroprotective activities of these diterpenes were investigated to explore potential anti-Alzheimer's disease (AD) bioactive lead compounds. In general, the lathyrane diterpenes showed the better acetylcholinesterase (AChE) inhibitory activity than that of premyrsinanes. The lathyrane derivative 17 bearing a 3-dimethylaminobenzoyl moiety showed the best AChE inhibition effect with the IC50 value of 7.1 µM. Molecular docking demonstrated that 17 could bond with AChE well (-8 kal/mol). On the other hand, premyrsinanes showed a better neuroprotection profile against H2O2-induced injury in SH-SY5Y cells. Among them, the premyrsinane diterpene 16a had significant neuroprotective effect with the cell viability rate of 113.5 % at 12.5 µM (the model group with 51.2 %). The immunofluorescence, western blot and reactive oxygen species (ROS) analysis were conducted to demonstrate the mechanism of 16a. Furthermore, a preliminary SAR analysis of the two categories of diterpenes was performed to provide the insights for anti-AD drug development.

Distribution and associations of anterior lens zonules lengths in patients with cataract.

PURPOSE: To investigate the characteristics and associations of anterior lens zonules lengths in cataract patients via ultrasound biomicroscope (UBM) measurement. METHODS: Patients with age-related cataracts and high myopic cataracts who planned to undergo cataract surgery were included in the study. After routine ophthalmic examinations, the UBM was performed on both eyes to get images of the anterior lens zonules, and Image J software was used to measure the lengths of the lens zonules. Axial length (AL), anterior chamber depth (ACD), lens thickness (LT), and white-to-white (WTW) diameter of both eyes were obtained by IOL Master 700. Univariate and multivariate regression analyses were used to assess associated factors of anterior lens zonules lengths. RESULTS: Forty-nine patients with age-related cataracts and 33 patients with high myopic cataracts were enrolled. High myopic cataract patients were younger and had longer anterior lens zonules. Multivariate regression analysis showed that anterior lens zonules lengths were associated with axial lengths (temporal location: ß = 0.036, P = 0.029; nasal location: ß = 0.034, P = 0.011; superior location: ß = 0.046, P = 0.002) and ACD (inferior location: ß = 0.305, P = 0.016) in right eyes. In left eyes, anterior lens zonules lengths were associated with axial lengths (temporal location: ß = 0.028, P = 0.017; inferior location: ß = 0.026, P = 0.016; nasal location: ß = 0.033, P < 0.001) and ACD (inferior location: ß = 0.215, P = 0.030; superior location: ß = 0.290, P = 0.011). CONCLUSIONS: High myopic cataract patients have longer anterior lens zonules. AL and ACD contributed to the lengths of anterior lens zonules. Thus, for patients with long AL and deeper ACD, lens zonules measurement was crucial. CLINICAL TRIAL REGISTRATION: www.chictr.org.cn identifier is ChiCTR2300071397.

Association of air pollution with incidence of elderly-onset seborrheic dermatitis: A prospective cohort study in UK Biobank.

BACKGROUND: Elderly-onset seborrheic dermatitis (SD) seriously affects the quality of life. However, associations between air pollution exposures and elderly-onset SD incidence have not been elucidated. OBJECTIVES: Investigate air pollution's role in the incidence of elderly-onset SD. METHODS: We engaged a prospective cohort analysis utilizing the UK Biobank database. Exposure data for specific air pollutants (PM2.5, PM2.5-10, NOX, NO2, and PM10) spanning various years was incorporated. Through a composite air pollution score constructed from five pollutants and employing Cox proportional hazards models, the relationship between pollution and SD was delineated. RESULTS: Our examination of 193,995 participants identified 3,363 SD cases. Higher concentrations of specific pollutants, particularly in the upper quartile (Q4), were significantly linked to an elevated SD risk. Notably, PM2.5, PM10, NO2, and NOX exhibited hazard ratios of 1.11, 1.15, 1.22, and 1.15, respectively. The correlation was further solidified with a positive association between air pollution score increments and SD onset. Intriguingly, this association was accentuated in certain demographics, including younger males, the socioeconomically deprived, smokers, daily alcohol consumers, and those engaging in regular physical activity. CONCLUSIONS: Our findings revealed that air pollution exposures were associated with elderly-onset SD incidence. These results emphasize the importance of preventing environmental exposures to the risk of SD development.

miR-16-5p aggravates sepsis-associated acute kidney injury by inducing apoptosis.

Sepsis-associated acute kidney injury (S-AKI) is a common disease in pediatric intensive care units (ICU) with high morbidity and mortality. The newly discovered results indicate that microRNAs (miRNAs) play an important role in the diagnosis and treatment of S-AKI and can be used as markers for early diagnosis. In this study, the expression level of miR-16-5p was found to be significantly upregulated about 20-fold in S-AKI patients, and it also increased by 1.9 times in the renal tissue of S-AKI mice. Receiver operating characteristic (ROC) curve analysis showed that miR-16-5p had the highest predictive accuracy in the diagnosis of S-AKI (AUC = 0.9188). In vitro, the expression level of miR-16-5p in HK-2 cells treated with 10 µg/mL lipopolysaccharide (LPS) increased by more than 2 times. In addition, LPS-exposed renal tissue and HK-2 cells lead to upregulation of inflammatory cytokines IL-6, IL-1ß, TNF-a, and kidney damage molecules kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL). However, inhibition of miR-16-5p significantly mitigated LPS expose-mediated kidney injury and inflammation. Furthermore, LPS-exposed HK-2 cells increased more than 1.7-fold the expression levels of Bax and caspase-3, decreased 3.2-fold the expression level of B-cell lymphoma-2 (Bcl-2), and significantly promoted the occurrence of apoptosis. MiR-16-5p mimic further increased LPS-induced apoptosis in HK-2 cells. Nevertheless, inhibition of miR-16-5p significantly attenuated this effect. In summary, up-regulation of miR-16-5p expression can significantly aggravate renal injury and apoptosis in S-AKI, which also proves that miR-16-5p can be used as a potential biomarker to promote early identification of S-AKI.

Rapid Determination of Tetracyclines in Drinking and Environmental Waters Using Fully Automatic Solid-Phase Extraction with Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry.

The abuse and irrational use of tetracyclines (TCs) in human medicine and animal husbandry has become a serious concern, affecting the ecological environment and human health. The aim of this study was to develop a sensitive and selective method using fully automatic solid-phase extraction coupled with ultra-performance liquid chromatography-tandem mass spectrometry for the determination of twelve TCs in water. Four isotope-labeled internal standards for TCs were used to correct matrix effects. Several parameters affecting extraction efficiency were systematically optimized, and the optimum experimental conditions found were 1.0 L water sample with 0.5 g/L Na2EDTA (pH 3.0) extracted and enriched by CNW HLB cartridge and eluted by 4 mL of acetone:methanol (v/v, 1:1). The enrichment factors were up to 798-1059 but only requiring about 60 min per six samples. Under the optimized conditions, the linearity of the method ranged from 0.2 to 100 µg/L for 12 TCs, the detection limits were as low as 0.01-0.15 ng/L, and the recoveries were in the range of 70%-118%, with relative standard deviations less than 15%. The developed method can be successfully utilized for the determination of 12 TCs in pure water, tap water, river water, and mariculture seawater. In summary, three and six TCs were detected in river water and mariculture seawater, respectively, with total concentrations of 0.074-0.520 ng/L (mean 0.248 ng/L) and 0.792-58.369 ng/L (12.629 ng/L), respectively. Tetracycline (TC) and oxytetracycline (OTC) were the dominant TCs in river water, while doxytetracycline (DXC) and OTC were dominant in mariculture seawater.

Transparent silicone-free shampoo containing proteins with strong hair conditioning properties.

OBJECTIVE: With the constant upgrading of healthcare concepts, silicone-free hair products have attracted more attention among consumers. In the present study, transparent silicone-free shampoo containing proteins was successfully fabricated by mixing mild non-sulphate surfactants, compound cationic conditioners, natural silicone oil substitutes, protein conditioners, thickeners, and other auxiliary ingredients. The effects of the type of surfactants, hair conditioners and thickeners, the type and content of proteins, and the mass ratio of compound proteins on the hair foaming performance, hair grooming performance, and penetration performance were investigated. METHODS: The basic formulation framework for transparent silicone-free shampoo was established at first. Then, various hydrolyzed proteins were further added to the basic formulation in the form of single use or compound use to prepare transparent silicone-free shampoo containing different proteins. The morphology of hair samples and penetration of protein in hair were evaluated with a scanning electron microscope and laser confocal fluorescence microscopy, respectively. And the hair grooming performance was also determined by a dynamic combing tester. RESULTS: The compound proteins of Croquat WKP PE-LQ-WD and Gluadin® Kera-PLM with mass ratios of 1:9 and 1:1 at 2 wt% total protein content added to the silicone-free shampoo brought a higher contact angle and a lower frictional coefficient than commercial silicone-free shampoo without proteins. In addition, the compound proteins also have the dual effect of adsorbing the hair surface and penetrating deep into the interior of the hair. CONCLUSION: The combination of cationic modified hydrolyzed protein (e.g., Croquat WKP PE-LQ-WD) and hydrolyzed protein with low molecular weight (e.g., Gluadin® Kera-P LM) at an appropriate mass ratio exhibited a strong synergistic effect on hair conditioning properties. It could provide a significant reference for developing silicone-free hair products with more benefits.

OBJECTIF: Avec l'amélioration constante des concepts de soins de santé, les produits capillaires sans silicone ont attiré l'attention des consommateurs. Dans la présente étude, un shampooing transparent sans silicone contenant des protéines a été fabriqué avec succès en mélangeant des tensioactifs doux sans sulfate, des conditionneurs cationiques composés, des substituts naturels de l'huile de silicone, des conditionneurs protéiques, des épaississants et d'autres ingrédients auxiliaires. On a étudié les effets du type de tensioactifs, de conditionneurs pour les cheveux et d'épaississants, du type et de la teneur en protéines et du rapport massique des protéines composées sur les performances de moussage des cheveux, du nettoyage des cheveux et de la pénétration. MÉTHODES: le cadre de formulation de base pour le shampooing transparent sans silicone a d'abord été établi. Ensuite, diverses protéines hydrolysées ont été ajoutées à la formulation de base sous forme d'utilisation unique ou d'utilisation de composés pour préparer un shampooing transparent sans silicone contenant différentes protéines. La morphologie des échantillons de cheveux et la pénétration des protéines dans les cheveux ont été évaluées à l'aide d'un microscope électronique a balayage et d'une microscopie confocale laser à fluorescence, respectivement. Les performances de nettoyage des cheveux ont également été déterminées par un testeur de peignage dynamique. RÉSULTATS: les protéines composées de Croquat WKP PE-LQ-WD et de GluadinR Kera-PLM avec des rapports massiques de 1:9 et 1:1 à 2 % en poids de teneur en protéines totales ajoutées au shampooing sans silicone ont un angle de contact plus élevé et un coefficient de frottement plus faible que le shampooing sans silicone commercial sans protéines. En outre, les protéines composées ont également doublé l'effet d'adsorption à la surface des cheveux et de pénétration à l'intérieur des cheveux. CONCLUSION: la combinaison de protéines hydrolysées modifiées cationiques (par exemple, Croquat WKP PE-LQ-WD) et de protéines hydrolysées de faible poids moléculaire (par exemple, GluadinR Kera-P LM) avec un rapport massique approprié a montré un fort effet synergique sur les propriétés de conditionnement des cheveux. Il pourrait fournir une référence significative pour le développement de produits capillaires sans silicone avec plus d'avantages.

Leveraging a cuproptosis-based signature to predict the prognosis and drug sensitivity of cutaneous melanoma.

Immunotherapy is a vital treatment for patients with cutaneous melanoma (CM), but effective predictors to guide clinical immunotherapy are lacking. Cuproptosis is a newly discovered mode of cell death related to tumorigenesis. Exploring the relationship between the mode of cuproptosis and the effect of immunotherapy on CM could better guide clinical management. We clustered all patients with CM in the Cancer Genome Atlas (TCGA) database based on cuproptosis-related genes (CRGs). Prognosis, immunotherapeutic effect, tumor microenvironment score, expression of CD274, CTLA4, and PDCD1, and abundance of CD8 + T infiltration in group A were higher than in group B. Using a combination of LASSO and COX regression analysis, we identified 10 molecules significant to prognosis from differentially expressed genes between the two groups and constructed a cuproptosis-related scoring system (CRSS). Compared with the American Joint Committee on Cancer (AJCC) staging system, CRSS more accurately stratified CM patient risk and guided immunotherapy. CRSS successfully stratified risk and predicted the effect of immunotherapy in 869 patients with eight CM immunotherapy datasets and multiple other tumor immunotherapy cohorts. The nomogram model, which combined AJCC stage and CRSS, greatly improved the ability and accuracy of prognosis prediction. In general, our cuproptosis-related scoring system and nomogram model accurately stratified risk in CM patients and effectively predicted prognosis and the effect of immunotherapy in CM patients.

Hexanuclear Ln6 L6 Complex Formation by Using an Unsymmetric Ligand.

Multinuclear, self-assembled lanthanide complexes present clear opportunities as sensors and imaging agents. Despite the widely acknowledged potential of this class of supramolecule, synthetic and characterization challenges continue to limit systematic studies into their self-assembly restricting the number and variety of lanthanide architectures reported relative to their transition metal counterparts. Here we present the first study evaluating the effect of ligand backbone symmetry on multinuclear lanthanide complex self-assembly. Replacement of a symmetric ethylene linker with an unsymmetric amide at the center of a homoditopic ligand governs formation of an unusual Ln6 L6 complex with coordinatively unsaturated metal centers. The choice of triflate as a counterion, and the effect of ionic radii are shown to be critical for formation of the Ln6 L6 complex. The atypical Ln6 L6 architecture is characterized using a combination of mass spectrometry, luminescence, DOSY NMR and EPR spectroscopy measurements. Luminescence experiments support clear differences between comparable Eu6 L6 and Eu2 L3 complexes, with relatively short luminescent lifetimes and low quantum yields observed for the Eu6 L6 structure indicative of non-radiative decay processes. Synthesis of the Gd6 L6 analogue allows three distinct Gd⋯Gd distance measurements to be extracted using homo-RIDME EPR experiments.

Impact of BMI on the survival outcomes of non-small cell lung cancer patients treated with immune checkpoint inhibitors: a meta-analysis.

OBJECTIVES: ICIs have become the standard treatment for advanced NSCLC patients. Currently, PD-L1 is the most widely useful biomarker to predict ICI efficacy, but the sensitivity and specificity are limited. Therefore, the useful predictive biomarkers of ICI efficacy is urgently needed. BMI is an internationally used measure of body health. Obesity may affect ICI efficacy by changing T cell functions. This meta-analysis aimed to clarify the relationship between BMI and survival outcomes of NSCLC patients treated with ICIs. METHODS: A systematic review was conducted to identify studies that assessed the association between BMI and survival outcomes in patients treated with ICIs. OS was the primary endpoint, and PFS was the secondary endpoint. Random-effect models or fixed-effect models were utilized to combine study effects according to the Cochran Q and I2 tests. RESULTS: Nine studies, including 4602 NSCLC patients treated with ICIs, that met the inclusion criteria were selected for this meta-analysis. There was no significant difference in PFS (HR 0.885; 95% CI 0.777-1.009, p = 0.068) or OS (HR 0.947; 95% CI 0.789-1.137, p = 0.560) between the low BMI group and the high BMI group. However, in the subgroup analysis, compared with normal-weight patients, overweight and obese patients achieved prolonged PFS (HR 0.862; 95% CI 0.760-0.978, p = 0.021) and OS (HR 0.818; 95% CI 0.741-0.902, p<0.0001). CONCLUSION: Overweight and obese NSCLC patients tend to achieve prolonged survival time with ICI regimens. Further prospective studies are needed to strengthen the association between ICI outcomes and BMI levels.