Predicting neurodevelopmental outcomes in extremely preterm neonates with low-grade germinal matrix-intraventricular hemorrhage using synthetic MRI.

Objectives: This study aims to assess the predictive capability of synthetic MRI in assessing neurodevelopmental outcomes for extremely preterm neonates with low-grade Germinal Matrix-Intraventricular Hemorrhage (GMH-IVH). The study also investigates the potential enhancement of predictive performance by combining relaxation times from different brain regions. Materials and methods: In this prospective study, 80 extremely preterm neonates with GMH-IVH underwent synthetic MRI around 38 weeks, between January 2020 and June 2022. Neurodevelopmental assessments at 18 months of corrected age categorized the infants into two groups: those without disability (n = 40) and those with disability (n = 40), with cognitive and motor outcome scores recorded. T1, T2 relaxation times, and Proton Density (PD) values were measured in different brain regions. Logistic regression analysis was utilized to correlate MRI values with neurodevelopmental outcome scores. Synthetic MRI metrics linked to disability were identified, and combined models with independent predictors were established. The predictability of synthetic MRI metrics in different brain regions and their combinations were evaluated and compared with internal validation using bootstrap resampling. Results: Elevated T1 and T2 relaxation times in the frontal white matter (FWM) and caudate were significantly associated with disability (p < 0.05). The T1-FWM, T1-Caudate, T2-FWM, and T2-Caudate models exhibited overall predictive performance with AUC values of 0.751, 0.695, 0.856, and 0.872, respectively. Combining these models into T1-FWM + T1-Caudate + T2-FWM + T2-Caudate resulted in an improved AUC of 0.955, surpassing individual models (p < 0.05). Bootstrap resampling confirmed the validity of the models. Conclusion: Synthetic MRI proves effective in early predicting adverse outcomes in extremely preterm infants with GMH-IVH. The combination of T1-FWM + T1-Caudate + T2-FWM + T2-Caudate further enhances predictive accuracy, offering valuable insights for early intervention strategies.

Effects of Acute High-Altitude Exposure on Morphology and Function of Retinal Ganglion Cell in Mice.

Purpose: High altitude retinopathy (HAR) is a retinal functional disorder caused by inadequate adaptation after exposure to high altitude. However, the cellular and molecular mechanisms underlying retinal dysfunction remain elusive. Retinal ganglion cell (RGC) injury is the most important pathological basis for most retinal and optic nerve diseases. Studies focusing on RGC injury after high-altitude exposure (HAE) are scanty. Therefore, the present study sought to explore both functional and morphological alterations of RGCs after HAE. Methods: A mouse model of acute hypobaric hypoxia was established by mimicking the conditions of a high altitude of 5000 m. After HAE for 2, 4, 6, 10, 24, and 72 hours, the functional and morphological alterations of RGCs were assessed using retinal hematoxylin and eosin (H&E) sections, retinal whole mounts, transmission electron microscopy (TEM), and the photopic negative response (PhNR) of the electroretinogram. Results: Compared with the control group, the thickness of the ganglion cell layer and retinal nerve fiber layer increased significantly, RGC loss remained significant, and the amplitudes of a-wave, b-wave, and PhNR were significantly reduced after HAE. In addition, RGCs and their axons exhibited an abnormal ultrastructure after HAE, including nuclear membrane abnormalities, uneven distribution of chromatin in the nucleus, decreased cytoplasmic electron density, widening and vacuolization of the gap between axons, loosening and disorder of myelin sheath structure, widening of the gap between myelin sheath and axon membrane, decreased axoplasmic density, unclear microtubule and nerve fiber structure, and abnormal mitochondrial structure (mostly swollen, with widened membrane gaps and reduced cristae and vacuolization). Conclusions: The study findings confirm that the morphology and function of RGCs are damaged after HAE. These findings lay the foundation for further study of the specific molecular mechanisms of HAR and promote the effective prevention.

[Corrigendum] Alcohol extracts from Anemone flaccida Fr. Schmidt treat rheumatoid arthritis via inhibition of synovial hyperplasia and angiogenesis.

Subsequently to the publication of the above paper, the authors drew to the attention of the Editorial Office that they had assembled the data shown for the cell migration assay experiments in Fig. 4F (on p. 8), incorrectly; essentially, the 'Control' data panel had inadvertently been copied across for the '10 µg/ml' data panel. The revised version of Fig. 4, showing the correct data panel for the '10 µg/ml' experiment in Fig. 4F,  is shown on the next page. Note that the replacement of the erroneous data does not affect either the results or the conclusions reported in this paper, and all the authors agree to the publication of this Corrigendum. The authors are grateful to the Editor of Molecular Medicine Reports for granting them this opportunity to publish a Corrigendum, and apologize to the readership for any inconvenience caused. [Molecular Medicine Reports 27: 88, 2023; DOI: 10.3892/mmr.2023.12975].

Development of human papillomavirus and its detection methods (Review).

Human papillomavirus (HPV) infection plays an important role in cervical cancer. HPV is classified within the Papillomaviridae family and is a non-enveloped, small DNA virus. HPV infection can be classified into two distinct scenarios: i) With or without integration into the host chromosomes. Detection of its infection can be useful in the study of cervical lesions. In the present review, the structural and functional features of HPV, HPV typing, infection and transmission mode, the risk factors for cervical susceptibility to infection and HPV detection methods are described in detail. The development of HPV detection methods may have far-reaching significance in the prevention and treatment of cervical disease. This review summarizes the advantages and limitations of each HPV detection method.

SARS-CoV-2 reinfection broadens the antibody responses and promotes the phenotypic differentiation of virus-specific memory T cells in adolescents.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariants raises concerns regarding the effectiveness of immunity acquired from previous Omicron subvariants breakthrough infections (BTIs) or reinfections (RIs) against the current circulating Omicron subvariants. In this study, we prospectively investigate the dynamic changes of virus-specific antibody and T cell responses among 77 adolescents following Omicron BA.2.3 BTI with or without subsequent Omicron BA.5 RI. Notably, the neutralizing antibodies (NAbs) titers against various detected SARS-CoV-2 variants, especially the emerging Omicron CH.1.1, XBB.1.5, XBB.1.16, EG.5.1, and JN.1 subvariants, exhibited a significant decrease along the time. A lower level of IgG and NAbs titers post-BTI was found to be closely associated with subsequent RI. Elevated NAbs levels and shortened antigenic distances were observed following Omicron BA.5 RI. Robust T cell responses against both Omicron BA.2- and CH.1.1-spike peptides were observed at each point visited. The exposure to Omicron BA.5 promoted phenotypic differentiation of virus-specific memory T cells, even among the non-seroconversion adolescents. Therefore, updated vaccines are needed to provide effective protection against newly emerging SARS-CoV-2 variants among adolescents.

Sprayable biomimetic double mask with rapid autophasing and hierarchical programming for scarless wound healing.

Current sprayable hydrogel masks lack the stepwise protection, cleansing, and nourishment of extensive wounds, leading to delayed healing with scarring. Here, we develop a sprayable biomimetic double wound mask (BDM) with rapid autophasing and hierarchical programming for scarless wound healing. The BDMs comprise hydrophobic poly (lactide-co-propylene glycol-co-lactide) dimethacrylate (PLD) as top layer and hydrophilic gelatin methacrylate (GelMA) hydrogel as bottom layer, enabling swift autophasing into bilayered structure. After photocrosslinking, BDMs rapidly solidify with strong interfacial bonding, robust tissue adhesion, and excellent joint adaptiveness. Upon implementation, the bottom GelMA layer could immediately release calcium ion for rapid hemostasis, while the top PLD layer could maintain a moist, breathable, and sterile environment. These traits synergistically suppress the inflammatory tumor necrosis factor-α pathway while coordinating the cyclic guanosine monophosphate/protein kinase G-Wnt/calcium ion signaling pathways to nourish angiogenesis. Collectively, our BDMs with self-regulated construction of bilayered structure could hierarchically program the healing progression with transformative potential for scarless wound healing.

Elemental and particle size fractionation during the transport of Eu(III)-silicate colloids in water-saturated porous media.

Actinides (An)-bearing colloids could facilitate An migration in the environment. However, little is known about the transport behavior of An(III)-silicate colloids, which are readily formed by the reaction of An3+ with silicic acid under environmental conditions. Column experiments were conducted to investigate the transport of Eu(III)-silicate colloids (chemical analog of An(III)-silicate colloids) in water-saturated porous media as a function of pH, ionic strength (IS) and the presence of fulvic acid (FA). The results showed that colloid transport was more favorable at relatively low IS (≤ 50 mM) and high pH levels (pH ≥ 7). The presence of FA (5-10 mg/L) significantly enhanced the colloid transport. Under high IS (≥ 100 mM), the transport feature of colloids was turned from blocking to ripening due to the on-going aggregation of colloids. Additionally, an interesting elemental fractionation, i.e., a discrepancy in the breakthrough curves (BTCs) with respect to the C/C0 values of Si and Eu, was observed in the IS of 100-500 mM. A detailed investigation indicated that the elemental fractionation could be attributed to the partial Si dissolution of the colloids, the heterogeneity of the colloid size and element composition, and particle size fractionation during colloid transport. Extended Derjaguin-Landau-Verwey-Overbeek interaction energy calculations and convective-dispersive equation modeling were performed to illustrate variations in the colloid transport profiles. These findings illustrate the importance of Si dissolution in the migration of metal-silicate colloids and highlight the significant influence of the heterogeneity of colloid size and composition on the transport/migration behavior of colloids in the environment.

Decoding the neural impact of radical complexity in Chinese characters during working memory task.

Readers of Chinese characters need to recognize how they are formed in order to identify them correctly. However, our understanding of the cognitive processing of characters in working memory is limited. In Experiment 1, using the character N-back task paradigm, electrophysiological data were recorded from 26 participants to investigate the effects of the visual feature of radicals on neural activity during the character recognition, updating and maintenance in the N-back task. Results showed that compound characters required longer response times than single-component characters. For the event-related potentials (ERPs), the compound character condition had more negative N2pc and lower P300 amplitudes than the single-component character condition. In Experiment 2, data from 26 participants were used to analyse the effect of the phonological feature of radicals on neural activity during the character recognition, updating and maintenance in the N-back task. Results showed that there was a larger P200 in the irregular character condition than in the regular character condition, but there was no difference between the regular and the irregular characters in the N2pc, P300 and slow wave (SW) components. The visual feature and the phonological feature of the radicals may have different effects on the character processing. This study reveals the neural effects of Chinese character radicals on cognitive processing in a working memory task and provides behavioural and electrophysiological evidence for a theoretical model of verbal working memory subprocesses.

Quercetin promotes the proliferation, migration, and invasion of trophoblast cells by regulating the miR-149-3p/AKT1 axis.

Recurrent spontaneous abortion (RSA) has a complex pathogenesis with an increasing prevalence and is one of the most intractable clinical challenges in the field of reproductive medicine. Quercetin (QCT) is an effective active ingredient extracted from Semen Cuscutae and Herba Taxilli used in traditional Chinese medicine for tonifyng the kidneys and promoting fetal restoration. Although QCT helps improve adverse pregnancy outcomes, the specific mechanism remains unclear. The trophoblast cell line HTR-8/SVneo cultured in vitro was treated with different concentrations of QCT, and the cell counting kit-8 assay, wound healing assay, transwell assay, and western blotting were used to evaluate the effects and mechanisms of QCT on the proliferation, migration, and invasion of HTR-8/SVneo cells, respectively. To assess the expression levels of miR-149-3p and AKT serine/threonine kinase 1 (AKT1), quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting analysis were performed. A dual-luciferase reporter assay was used to investigate the potential regulatory relationship between miR-149-3p and AKT1. Our results showed that QCT promoted the proliferation, migration, and invasion of trophoblast cells, promoted the expression of MMP2, MMP9, and vimentin, and downregulated the expression of E-cadherin. Mechanistically, QCT downregulated the expression of miR-149-3p and upregulated the expression of AKT1, and miR-149-3p directly targets AKT1, negatively regulating its expression. Overexpression of miR-149-3p and silencing of AKT1 counteracted the promotional effects of QCT on trophoblast proliferation, migration, and invasion. Taken together, QCT regulates the migration and invasion abilities of HTR-8/SVneo cells through the miR-149-3p/AKT1 axis, which may provide a promising therapeutic approach for RSA.

Silane modified Cr2O3/polyimide nanocomposite films with excellent surface insulation performance for space applications.

The exploration of deep space significantly increases the probability of spacecraft failures due to surface electrostatic discharge, which imposes higher vacuum insulation protection requirements on polyimide, the external insulation material of spacecrafts. To address this challenge, this study proposes using silane coupling agent KH550 for organic grafting treatment of Cr2O3 nanoparticles, which are then used to dope and modify polyimide to enhance the vacuum surface insulation of polyimide films. The KH550 grafting improves the interface strength between the fillers and the matrix, allowing the fillers to be uniformly dispersed in the matrix. Compared to pure polyimide films, the prepared PI-Cr2O3@KH550 composite films exhibit significantly enhanced vacuum surface flashover voltage, improved surface/volume resistivity, and dielectric properties. The results demonstrate that polyimide composite films with 0.8% by mass of Cr2O3@KH550 show the most notable performance improvement, with the DC flashover voltage and impulse flashover voltage in vacuum increasing by 20.7% and 27.8%, respectively. The doping of chromium oxide nanoparticles introduces more deep traps into the polyimide films and reduce the surface resistivity. The higher deep trap density inhibits charge migration, thereby alleviating secondary electron emission and surface electric field distortion. Simultaneously, the lower surface resistivity facilitates dissipating surface charges and improves the surface insulation. These findings are of significant reference value for promoting the enhancement of aerospace insulation performance.

Benefit delayed immunosenescence by regulating CD4+T cells: A promising therapeutic target for aging-related diseases.

CD4+T cells play a notable role in immune protection at different stages of life. During aging, the interaction between the body's internal and external environment and CD4+T cells results in a series of changes in the CD4+T cells pool making it involved in immunosenescence. Many studies have extensively examined the subsets and functionality of CD4+T cells within the immune system, highlighted their pivotal role in disease pathogenesis, progression, and therapeutic interventions. However, the underlying mechanism of CD4+T cells senescence and its intricate association with diseases remains to be elucidated and comprehensively understood. By summarizing the immunosenescent progress and network of CD4+T cell subsets, we reveal the crucial role of CD4+T cells in the occurrence and development of age-related diseases. Furthermore, we provide new insights and theoretical foundations for diseases targeting CD4+T cell subsets aging as a treatment focus, offering novel approaches for therapy, especially in infections, cancers, autoimmune diseases, and other diseases in the elderly.

ROR2 promotes cell cycle progression and cell proliferation through the PI3K/AKT signaling pathway in gastric cancer.

Proliferation is a critical characteristic of the progression of gastric cancer (GC). Receptor tyrosine kinase-like orphan receptor 2 (ROR2), the orphan receptor tyrosine kinase-like receptor, exhibits effects on tumor growth due to its abnormal expression in cancer. The goal of our study was to assess the potential regulatory role exerted by the ROR2 on GC cells. Through previous bioinformatics analysis, we discovered an association between ROR2 and the G2/M phase of the GC cell cycle. However, little is known about the link between ROR2 and the G2/M phase cell cycle in GC. Here, the findings of our study indicate that ROR2, after transcribed expression by Twist1, activates the PI3K/AKT/mTOR/S6K signal transduction pathway, thus leading to the acceleration of the G2/M phase and subsequent promotion of cell proliferation in GC. Furthermore, the functional link among ROR2, Twist1, and G2/M phase of cell cycle was also confirmed in mouse xenograft tissues and human tissues. ROR2 expression was correlated with Twist expression and lower survival in vivo. Notably, our suggestion is that focusing on ROR2 as a potential therapeutic approach could show potential for the management of GC.

Unveiling the role of RhoA and ferroptosis in vascular permeability: Implications for osteoarthritis.

Abnormal angiogenesis and increased vascular permeability of subchondral bone are key mechanisms related to osteoarthritis (OA). However, the precise mechanisms responsible for heightened vascular permeability in OA remain unclear. The present study used proteomics to identify protein expression in damaged subchondral bone compared with normal subchondral bone. The results suggest that Ras homolog family member A (RhoA) may be associated with the vascular permeability of subchondral bone and ferroptosis in OA. The results of analysis of clinical samples indicated a significant increase in expression of RhoA in the subchondral bone of OA. This were consistent with the proteomics findings. We found through western blotting, RT­PCR, and immunofluorescence that RhoA significantly increased the permeability of endothelial cells (ECs) by inhibiting inter­EC adhesion proteins (zona occludens­1, connexin 43 and Vascular endothelial­Cadherin) and actin filaments. Furthermore, RhoA induced ferroptosis core proteins (glutathione peroxidase 4,  solute carrier family 7 member 11 and acyl­CoA synthase long­chain family member 4, ACSL4) by influencing lipid peroxidation and mitochondrial function, leading to ferroptosis of ECs. This suggested an association between RhoA, ferroptosis and vascular permeability. Ferroptosis significantly increased permeability of ECs by inhibiting inter­EC adhesion proteins. RhoA increased vascular permeability by inducing ferroptosis of ECs. In vivo, inhibition of RhoA and ferroptosis significantly mitigated progression of OA by alleviating cartilage degeneration and subchondral bone remodeling in mice with destabilization of the medial meniscus. In conclusion, the present findings indicated that RhoA enhanced vascular permeability in OA by inducing ferroptosis. This may serve as a novel strategy for the early prevention and treatment of OA.

First-line treatment of severe aplastic anemia: immunosuppressive therapy plus eltrombopag versus haploidentical hematopoietic stem cell transplantation, a multicenter prospective study.

Matched-related donor hematopoietic stem cell transplantation (HSCT) remains the preferred first-line option for severe aplastic anemia (SAA) patients aged <40 years even in the era of eltrombopag (EPAG). However, there has not been any direct comparison between immunosuppressive therapy (IST) plus EPAG (IST + EPAG) and haploidentical HSCT (Haplo-HSCT) as first-line therapy. This study prospectively compared the efficacy, safety and health-related quality of life (HRQoL) of Haplo-HSCT (n = 147) and IST + EPAG (n = 121) as first-line treatment for patients with SAA. The results showed that 86.3% of patients in the Haplo-HSCT group and 24.1% of patients in the IST + EPAG group achieved normal complete blood count (CBC) (P < 0.001) after 6 months of treatment. The time to achieve transfusion independence and absolute neutrophil count ≥ 1.0 × 109/L were shorter in the Haplo-HSCT group than in the IST + EPAG group (P < 0.05). In the IST + EPAG and Haplo-HSCT, 3-year overall survival (OS) was 92.4 ± 2.4% and 82.8 ± 3.1% (P = 0.017), whereas 3-year failure-free survival (FFS) was 69.4 ± 4.2% and 81.6 ± 3.2% (P = 0.002), respectively. Similar results were observed in patients with <40 years of age. Among patients with ≥40 years of age, there was no difference in 3-year OS (88.6 ± 4.8% vs. 82.4 ± 8.1%, P = 0.517) between the IST + EPAG and Haplo-HSCT groups, whereas 3-year FFS was lower in the IST + EPAG (58.7 ± 7.5% vs. 82.4 ± 8.1%, P = 0.043). Subgroup analysis for populations aged <40 years indicated that SAA benefited more from IST + EPAG, and very SAA (vSAA) benefited more from Haplo-HSCT. Patients treated with haplo-HSCT scored significantly better in the HRQoL than treated with IST + EPAG (P < 0.0001). Multivariate analysis showed that first-line Haplo-HSCT was associated with normal CBC at 6 months, better FFS and led to a better HRQoL (P < 0.001). In summary, the IST + EPAG achieved better OS for <40 years SAA patients, while the Haplo-HSCT accelerated hematopoietic recovery and HRQoL, achieved better FFS even for those <40 years vSAA and ≥40 years patients.

High-Entropy-Inspired Multicomponent Electrical Double Layer Structure Design for Stable Zinc Metal Anodes.

Regulating the electrical double layer (EDL) structure can enhance the cycling stability of Zn metal anodes, however, the effectiveness of this strategy is significantly limited by individual additives. Inspired by the high-entropy (HE) concept, we developed a multicomponent (MC) EDL structure composed of La3+, Cl-, and BBI anions by adding dibenzenesulfonimide (BBI) and LaCl3 additives into ZnSO4 electrolytes (BBI/LaCl3/ZnSO4). Specifically, La3+ ions accumulate within EDL to shield the net charges on the Zn surface, allowing more BBI anions and Cl- ions to enter this region. Consequently, this unique MC EDL enables Zn anodes to simultaneously achieve uniform electric field, robust SEI layer, and balanced reaction kinetics. Moreover, the synergistic parameter-a novel descriptor for quantifying collaborative improvement-was first proposed to demonstrates the synergistic effect between BBI and LaCl3 additives. Benefitting from these advantages, Zn metal anodes achieved a high reversibility of 99.5% at a depth of discharge (DoD) of 51.3%, and Zn|MnO2 pouch cells exhibited a stable cycle life of 100 cycles at a low N/P ratio of 2.9.

Do bats' social vocalizations conform to Zipf's law and the Menzerath-Altmann law?

The study of vocal communication in non-human animals can uncover the roots of human languages. Recent studies of language have focused on two linguistic laws: Zipf's law and the Menzerath-Altmann law. However, whether bats' social vocalizations follow these linguistic laws, especially Menzerath's law, has largely been unexplored. Here, we used Asian particolored bats, Vespertilio sinensis, to examine whether aggressive vocalizations conform to Zipf's and Menzerath's laws. Aggressive vocalizations of V. sinensis adhere to Zipf's law, with the most frequent syllables being the shortest in duration. There was a negative association between the syllable number within a call and the average syllable duration, in agreement with Menzerath's law. A decrease in the proportion of some long syllables and a decrease in the duration of several syllable types in long-duration calls explain the occurrence of this law. Our results indicate that a general compression principle organizes aspects of bat vocal communication systems.

Identification of Key Genes and Signaling Pathways in Entrectinibresistant Non-small Cell Lung Cancer Using Bioinformatic Analysis and Experimental Verification.

BACKGROUND: Entrectinib, a ROS1 inhibitor, is effective in patients with ROS1-positive non-small-cell lung cancer (NSCLC). However, entrectinib resistance remains a challenge worldwide. The biomarkers of entrectinib resistance and molecular mechanisms have not been clarified based on the Gene Expression Omnibus (GEO) database. OBJECTS: The aim of this study is to identify key genes and signaling pathways involved in the development of entrectinib-resistant NSCLC through bioinformatics analysis and experimental validation. METHODS: Differentially expressed genes (DEGs) were screened between entrectinib resistant and parental human NSCLC cell lines of the GSE214715 dataset, lung adenocarcinoma (LUAD) and non-tumor adjacent tissues of the GSE75037 dataset, and NSCLC and non-tumor adjacent tissues of the GSE18842 dataset. Functional enrichment analyses were performed, including Gene Ontology (GO) term and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Overlapped DEGs among those three datasets were identified using the Venn diagram package. The transcriptional levels of key genes were investigated using the University of ALabama at Birmingham CANcer data analysis Portal (UALCAN). The association between transcriptional levels of key genes and survival was analyzed using Kaplan-Meier Plotter (https://www.kmplot.com/analysis/). The correlations between hub genes and immune cell infiltration were investigated using the Tumor Immune Estimation Resource (TIMER) database. Specific signaling pathway enrichment analysis was performed using Gene Set Enrichment Analysis (GSEA) of LinkedOmics. Competitive endogenous RNA (ceRNA) networks, genome-wide association studies (GWAS), and drug sensitivity analyses of key genes were further investigated. The expression of ZEB2 was subsequently confirmed in both parental HCC78 cells and entrectinib-resistant HCC78 cells using real-time quantitative polymerase chain reaction (qRT-PCR). RESULTS: 708 DEGs were identified between entrectinib-resistant CUTO28 (CUTO28-ER) and parental CUTO28 cell lines in the GSE214715 dataset. One thousand three hundred and ninety-five DEGs were identified between entrectinib resistant (CUTO37-ER) and parental CUTO37 cell lines in the GSE214715 dataset. Eight hundred and forty-nine DEGs were identified between LUAD and non-tumor adjacent tissues in the GSE75037 dataset. Seven hundred and sevety-three DEGs were identified between NSCLC and non-tumor adjacent tissues in the GSE18842 dataset. Among these three datasets, seven overlapped DEGs were identified, including ZBED2, CHI3L2, CELF2, SEMA5A, ZEB2, S100A12, and PDK4. Among these seven overlapped DEGs, the expression levels of CHI3L2, ZEB2, and S100A12 were downregulated in those three datasets. The results of analysis using the UALCAN database showed that these three genes were significantly downregulated in LUAD and LUSC patients compared with the normal population. However, only the lower transcriptional level of ZEB2 was linked to worse survival in patients with lung cancer. GSEA analysis revealed that ZEB2 was significantly negatively correlated with nucleotide excision repair (NER) in LUAD, and homologous recombination (HR) and NER in LUSC, which were linked to drug resistance. A ceRNA network of THRB-AS1/ has-miR-1293/ ZEB2 in LUAD was established. CONCLUSION: We have identified core genes associated with non-small cell resistance to entrectinib, including CHI3L2, ZEB2, and S100A12. ZEB2 is a core gene associated with acquired resistance to entetinib in NSCLC.

Azobenzene-bridged Covalent Organic Frameworks Boosting Photocatalytic Hydrogen Peroxide Production from Alkaline Water: One Atom Makes a Significant Improvement.

Covalent organic frameworks (COFs) have been demonstrated as promising photocatalysts for hydrogen peroxide (H2O2) production. However, the construction of COFs with new active sites, high photoactivity, and wide-range light absorption for efficient H2O2 production remains challenging. Herein, we present the synthesis of a novel azobenzene-bridged 2D COF (COF-TPT-Azo) with excellent performance on photocatalytic H2O2 production under alkaline conditions. Notably, although COF-TPT-Azo differs by only one atom (-N=N- vs. -C=N-) from its corresponding imine-linked counterpart (COF-TPT-TPA), the COF-TPT-Azo exhibits a significantly narrower band gap, enhanced charge transport, and prompted photoactivity. Remarkably, when employed as a metal-free photocatalyst, COF-TPT-Azo achieves a high photocatalytic H2O2 production rate up to 1498 µmol g-1 h-1 at pH =11, which is 7.9 times higher than that of COF-TPT-TPA. Further density functional theory (DFT) calculations reveal that the -N=N- linkages are the active sites for photocatalysis. This work provides new prospects for developing high-performance COF-based photocatalysts.

Triglyceride-glycaemic index: Insights into predicting fetal macrosomia and its interaction with gestational diabetes mellitus: A cohort study of Chinese pregnant women.

OBJECTIVE: This study investigates the association between a new insulin resistance indicator, the triglyceride-glucose (TyG) index, and the risk of macrosomia. DESIGN: This is a prospective cohort study. METHODS: This study included 1332 women who delivered at Peking University International Hospital between October 2017 and August 2019. Participants were divided equally into three groups based on the TyG index. Logistic regression and restricted cubic spline (RCS) analyses were used to evaluate the relationship between the TyG index and macrosomia and conducted subgroup analyses. The TyG index's ability to predict macrosomia was assessed using the receiver operating characteristic (ROC) curve. RESULTS: Multivariable logistic regression analysis revealed that the TyG index is an independent risk factor for macrosomia (Odds ratio [OR] 1.84, 95% confidence interval [CI] 1.02-3.30, p < .05). RCS analysis indicates that the risk of macrosomia increases with the rise of the TyG index (p for nonlinearity <.001) when the TyG index is >6.53. Subgroup analysis showed a synergistic additive interaction between the TyG index and gestational diabetes mellitus (GDM) of macrosomia. The area under the ROC curve for the predictive model was 0.733 (95% CI 0.684, 0.781), with a sensitivity of 76.4% and specificity of 66.9%. Incorporating the TyG index alongside traditional risk factors notably enhances macrosomia prediction (p < .05). CONCLUSIONS: The TyG index independently predicts macrosomia, and exhibits an additive interaction with GDM in its occurrence. Integrating the TyG index with traditional risk factors improves the prediction of macrosomia. TRIAL REGISTRY: Clinical trials. gov [NCT02966405].

Human and rat gonadal 3ß-hydroxysteroid dehydrogenases are suppressed by dithiocarbamate fungicides via interacting with cysteine residues.

Dithiocarbamates have been widely used in various industrial applications, such as insecticides (ferbam) or drug (disulfiram). This study explored the inhibitory effects of dithiocarbamates on human and rat gonadal 3ß-hydroxysteroid dehydrogenases (3ß-HSD) and investigated the structure-activity relationship and mechanistic insights. The inhibitory activity of six dithiocarbamates and thiourea on the conversion of pregnenolone to progesterone was evaluated using human KGN cell and rat testicular microsomes, with subsequent progesterone measurement using HPLC-MS/MS. The study found that among the tested compounds disulfiram, ferbam, and thiram exhibited significant inhibitory activity against human 3ß-HSD2 and rat 3ß-HSD1, with ferbam demonstrating the highest potency. The mode of action for these compounds was characterized, showing mixed inhibition for human 3ß-HSD2 and mixed/noncompetitive inhibition for rat 3ß-HSD1. Additionally, it was observed that dithiothreitol dose-dependently reversed the inhibitory effects of dithiocarbamates on both human and rat gonadal 3ß-HSD enzymes. The study also delved into the penetration of these dithiocarbamates through the human KGN cell membrane and their impact on progesterone production, highlighting their potency in inhibiting human 3ß-HSD2. Furthermore, bivariate correlation analysis revealed a positive correlation of LogP (lipophilicity) with IC50 values for both enzymes. Docking analysis indicated that dithiocarbamates bind to NAD+ and steroid-binding sites, with some interactions with cysteine residues. In conclusion, this study provides valuable insights into the structure-activity relationship and mechanistic aspects of dithiocarbamates as inhibitors of human and rat gonadal 3ß-HSDs, suggesting that these compounds likely exert their inhibitory effects through binding to cysteine residues.