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The equations of state and phase stabilities of high-entropy alloys (HEAs) under high-pressure and high-temperature conditions are of paramount importance for engineering applications. However, few reports exist on the high-pressure–temperature properties of the HfNbMoTaWV HEA system. Herein, we synthesized a NbMoTaW HEA using the vacuum arc melting method and measured its Hugoniot up to 143 GPa and ∼6200 K. A linear relationship [US = 2.61 (7) + 1.59 (5) UP] between the shock (US) and particle (UP) velocities was observed for UP > 0.7 km/s, suggesting that the NbMoTaW HEA is likely stable within the pressure–temperature range of the current study. Using the Debye–Mie–Grüneisen model and Birch–Murnaghan equation of state (EOS), we discussed the EOS of the NbMoTaW HEA. The bulk modulus (K0) and its pressure derivative (K0′) were determined to be 238 GPa and 3.3, respectively. We also found that the Hugoniot compression curve of the NbMoTaW HEA could be evaluated using the mixture rules with the Hugoniot data of the compositional elements. [ABSTRACT FROM AUTHOR]

Direct ammonia oxidation (Dirammox) might be of great significance to advance the innovation of biological nitrogen removal process in wastewater treatment systems. However, it remains unknown whether Dirammox bacteria can be selectively enriched in activated sludge. In this study, a lab-scale bioreactor was established and operated for 2 months to treat synthetic wastewater with hydroxylamine as a selection pressure. Three Dirammox strains (Alcaligenes aquatilis SDU_AA1, Alcaligenes aquatilis SDU_AA2, and Alcaligenes sp. SDU_A2) were isolated from the activated sludge, and their capability to perform Dirammox process was confirmed. Although these three Dirammox bacteria were undetectable in the seed sludge (0%), their relative abundances rapidly increased after a month of operation, reaching 12.65%, 0.69%, and 0.69% for SDU_A2, SDU_AA1, and SDU_AA2, respectively. Among them, the most dominant Dirammox (SDU_A2) exhibited higher nitrogen removal rate (32.35%) than the other two strains (13.57% of SDU_AA1 and 14.52% of SDU_AA2). Comparative genomic analysis demonstrated that the most dominant Dirammox bacterium (SDU_A2) possesses fewer complete metabolic modules compared to the other two less abundant Alcaligenes strains. Our findings expanded the understanding of the application of Dirammox bacteria as key functional microorganisms in a novel biological nitrogen and carbon removal process if they could be well stabilized. Key points: • Dirammox-dominated microbial community was enriched in activated sludge bioreactor. • The addition of hydroxylamine played a role in Dirammox enrichment. • Three Dirammox bacterial strains, including one novel species, were isolated. [ABSTRACT FROM AUTHOR]

Summary Chronic refractory primary immune thrombocytopenia (CRITP) is currently defined as refractory to multiple therapeutic of second‐line agents with or without splenectomy, faced with the threat of severe bleeding and challenging to obtain effective treatment. Although stable and effective drug therapy is needed, it is tough to find one. Daratumumab (Dara), an anti‐CD38 monoclonal antibody presented the target cloned plasma cells in multiple myeloma, has also been reported to be effective in refractory autoimmune cytopenia in some case or series reports and ongoing clinical trials for adult patients with CRITP. Here, we report the early and durable response of Dara combination with avatrombopag in three CRITP patients (2 male and 1 female aged 12, 5 and 7 years, respectively) in our centre, with a follow‐up period of more than 25 weeks. Before Dara, the duration of immune thrombocytopenia was 9, 1.4 and 4 years, respectively, a baseline platelet count of 4, 6, 9 × 109/L, the bleeding score was all above level 2 and the number of previous drugs was >3. The time to response (R: Plt ≥30 × 109/L with at least a twofold increase in the baseline count) of Dara was on Day 45, 6 and 4 and achieved complete response (CR: Plt ≥100 × 109/L) on Day 51, 6 and 8, the sustained response (SR: Plt >30 × 109/L following Dara at ≥75% of the platelet count assessment at follow‐up end‐point since the patient achieved response) was 48, 175 and 204 days with the follow‐up time of 39.1, 25.9 and 29.7 weeks. The bleeding score decreased from grade 3 to grade 0 during follow‐up. No significant treatment‐related adverse events were found during follow‐up. Dara combination with avatrombopag may be a safe and efficacious therapy for children with CRITP, but it needs to be further explored. [ABSTRACT FROM AUTHOR]

Background: Angiogenesis is critical for forming new blood vessels from antedating vascular vessels. The endothelium is essential for angiogenesis, vascular remodelling and minimisation of functional deficits following ischaemia. The insulin‐like growth factor (IGF) family is crucial for angiogenesis. Insulin‐like growth factor‐binding protein 5 (IGFBP5), a binding protein of the IGF family, may have places in angiogenesis, but the mechanisms are not yet completely understood. We sought to probe whether IGFBP5 is involved in pathological angiogenesis and uncover the molecular mechanisms behind it. Methods and results: IGFBP5 expression was elevated in the vascular endothelium of gastrocnemius muscle from critical limb ischaemia patients and hindlimb ischaemic (HLI) mice and hypoxic human umbilical vein endothelial cells (HUVECs). In vivo, loss of endothelial IGFBP5 (IGFBP5EKO) facilitated the recovery of blood vessel function and limb necrosis in HLI mice. Moreover, skin damage healing and aortic ring sprouting were faster in IGFBP5EKO mice than in control mice. In vitro, the genetic inhibition of IGFBP5 in HUVECs significantly promoted tube formation, cell proliferation and migration by mediating the phosphorylation of IGF1R, Erk1/2 and Akt. Intriguingly, pharmacological treatment of HUVECs with recombinant human IGFBP5 ensued a contrasting effect on angiogenesis by inhibiting the IGF1 or IGF2 function. Genetic inhibition of IGFBP5 promoted cellular oxygen consumption and extracellular acidification rates via IGF1R‐mediated glycolytic adenosine triphosphate (ATP) metabolism. Mechanistically, IGFBP5 exerted its role via E3 ubiquitin ligase Von Hippel‐Lindau (VHL)‐regulated HIF1α stability. Furthermore, the knockdown of the endothelial IGF1R partially abolished the reformative effect of IGFBP5EKO mice post‐HLI. Conclusion: Our findings demonstrate that IGFBP5 ablation enhances angiogenesis by promoting ATP metabolism and stabilising HIF1α, implying IGFBP5 is a novel therapeutic target for treating abnormal angiogenesis‐related conditions. [ABSTRACT FROM AUTHOR]

Graphene is regarded as a promising additive to enhance the thermal conductivity of bentonite in the geological repository, yet the hydro-mechanical properties of its mixture with bentonite under chemical conditions remain unclear. This work examined the one-dimensional swelling deformation of high-density graphene-modified bentonite (GMB) in NaCl solutions, considering the influences of graphene content and NaCl concentration. Results indicate that both graphene and NaCl reduced the maximum swelling strain and the primary and secondary swelling coefficients of GMB. Additionally, graphene enhanced the stability of swelling deformation in bentonite across various NaCl concentrations and decreased the GMB’s test duration. The relationship between test duration and NaCl concentration was nonmonotonic. The ratio of swelling strain at each stage to total swelling strain was rarely affected by graphene content or NaCl solution. Scanning electron microscope examinations on selected samples post-swelling tests unveiled a unique soil structure in GMB. Furthermore, a model was put forward to predict the maximum swelling strain of GMB inundated in NaCl solutions, and its feasibility was verified. [ABSTRACT FROM AUTHOR]

Organic-inorganic methylammonium lead iodide perovskite (MAPbI3) nanowires (NWs) have attracted significant attention in the realm of optoelectronic devices due to their outstanding optoelectronic properties. However, the persistent challenge of high trap densities has been a limiting factor in realizing their full potential in device performance. To address this challenge, we incorporated cesium (Cs) and systematically investigated the impact of Cs concentration on the trap densities and the optoelectronic characteristics of Cs x MA(1− x)PbI3 NWs. Our findings unveiled an initial reduction in trap densities as Cs+ content increased, with the lowest point occurring at x = 0.2. However, beyond this threshold, trap densities began to rise, eventually surpassing those observed in pure MAPbI3 at x = 0.4. Furthermore, we fabricated single NW photodetectors to assess how Cs+ content influenced optoelectronic properties. The results indicated that Cs+ incorporation led to enhancements in photocurrent and response speed, withthe optimal performance observed at x = 0.2. Our study provides valuable insights into the role of Cs+ incorporation in tailoring the optoelectronic properties of perovskite NWs. [ABSTRACT FROM AUTHOR]

As a key factor in determining testis size and sperm number, sertoli cells (SCs) play a crucial role in male infertility. Heat stress (HS) reduces SCs counts, negatively impacting nutrient transport and supply to germ cells, and leading to spermatogenesis failure in humans and animals. However, how HS affects the number of SCs remains unclear. We hypothesized that changes in SC metabolism contribute to the adverse effects of HS. In this study, we first observed an upregulation of arachidonic acid (AA), an unsaturated fatty acid after HS exposure by LC-MS/MS metabolome detection. By increasing ROS levels, expression of KEAP1 and NRF2 proteins as well as LC3 and LAMP2, 100 µM AA induced autophagy in SCs by activating oxidative stress (OS). We observed adverse effects of AA on mitochondria under HS with a decrease of mitochondrial number and an increase of mitochondrial membrane potential (MMP). We also found that AA alternated the oxygen transport and absorption function of mitochondria by increasing glycolysis flux and decreasing oxygen consumption rate as well as the expression of mitochondrial electron transport chain (ETC) proteins Complex I, II, V. However, pretreatment with 5 mM NAC (ROS inhibitor) and 2 µM Rotenone (mitochondrial ETC inhibitor) reversed the autophagy induced by AA. In summary, AA modulates autophagy in SCs during HS by disrupting mitochondrial ETC function, inferring that the release of AA is a switch-like response, and providing insight into the underlying mechanism of high temperatures causing male infertility. [ABSTRACT FROM AUTHOR]

AbstractIn the Marine environment, the invasion of various harmful ions (e.g., Na+, and Cl−) into the concrete can lose and deteriorate the interfacial transition zone (ITZ) which is the weakest area in concrete. The degradation of ITZ results in a decline in the mechanical performance and durability of concrete, making it crucial to study how to improve the stability of the interface transition zone. In this paper, a systematic review of the modification mechanisms of five different types of zero-dimensional nanoparticles in the ITZ was investigated, focusing on mechanical properties and durability. The evolution and deterioration of the ITZ in concrete in the Marine environment were studied, and also the modification mechanism of nanomaterials on this deterioration. The results indicate that the addition of nanoparticles to enhance the microstructure of ITZ can effectively improve the performance of the interface transition zone. This is primarily achieved through mechanisms such as filling effect, nucleation effect, and hydration promotion. These findings lay the foundation for future exploration of cement-based materials in marine environments. [ABSTRACT FROM AUTHOR]

Numerous synaptic devices have been explored for the next generation of energy‐efficient computing techniques. Among them, optoelectronic synaptic devices based on semiconductor/ferroelectric heterostructures have received a lot of attention lately due to their amazing parallelism, efficiency, and fault tolerance properties. However, polarizing the ferroelectric layer or gating the dielectric layer is necessary to achieve tunable synaptic functions, which generally causes an increase in energy consumption and complex manufacturing processes. Here, a simple and efficient method is demonstrated to develop a tunable optoelectronic synaptic device based on a single ferroelectric semiconductor, BiFeO3‐BaTiO3 (BF‐BT). Multi‐essential synaptic functions including short‐term plasticity, paired‐pulse facilitation, and long‐term plasticity are all satisfactorily replicated by the memristor device. More significantly, light‐controllable synaptic behaviors are realized by altering the ferroelectric polarization state of BF‐BT. Synaptic devices' relaxation characteristics enable simulation of the effects of positive/negative emotions on learning and forgetting processes. This study highlights the potential of the ferroelectric semiconductor memristor in constructing the efficient optoelectronic synapses for future neuromorphic electronics with the ability to learn and sense optical information. [ABSTRACT FROM AUTHOR]

We conducted a systematic investigation into the spectral and pulse characteristics of C and L-band Nonlinear Polarization Rotation (NPR) mode-locked fiber lasers effectively employing nonlinear polarization rotation technology. In our experimental setup, we achieved a stable mode-locked state at 1560.076 nm, exhibiting a 3 dB spectral bandwidth of 9.1 nm. As the pump power increased, we observed spectral shifts accompanied by shifts in the first Kelly sideband and the generation of new Kelly sidebands. In this paper, the phenomenon of spectral deviation is elucidated through the interplay of self-phase modulation, group velocity drift, and polarization-dependent isolator (PD-ISO) filter effect, with an analysis of the formation and deviation of Kelly sidebands. Notably, spectral shift persisted even when the pump power exceeded 200 mW. However, continuous pump power escalation led to soliton splitting, resulting in the formation of new soliton beams. Based on the simultaneous generation of spectral shift and pulse splitting, our study contributes to an enhanced understanding of soliton dynamics in ultrafast fiber lasers and lays a foundation for the application of high-repetition-frequency harmonic mode-locked lasers with tunable wavelengths. [ABSTRACT FROM AUTHOR]

Background: Accurate differentiation of extremity soft-tissue tumors (ESTTs) is important for treatment planning. Purpose: To develop and validate an ultrasound (US) image-based radiomics signature to predict ESTTs malignancy. Material and Methods: A dataset of US images from 108 ESTTs were retrospectively enrolled and divided into the training cohort (78 ESTTs) and validation cohort (30 ESTTs). A total of 1037 radiomics features were extracted from each US image. The most useful predictive radiomics features were selected by the maximum relevance and minimum redundancy method, least absolute shrinkage, and selection operator algorithm in the training cohort. A US-based radiomics signature was built based on these selected radiomics features. In addition, a conventional radiologic model based on the US features from the interpretation of two experienced radiologists was developed by a multivariate logistic regression algorithm. The diagnostic performances of the selected radiomics features, the US-based radiomics signature, and the conventional radiologic model for differentiating ESTTs were evaluated and compared in the validation cohort. Results: In the validation cohort, the area under the curve (AUC), sensitivity, and specificity of the US-based radiomics signature for predicting ESTTs malignancy were 0.866, 84.2%, and 81.8%, respectively. The US-based radiomics signature had better diagnostic predictability for predicting ESTT malignancy than the best single radiomics feature and the conventional radiologic model (AUC = 0.866 vs. 0.719 vs. 0.681 for the validation cohort, all P <0.05). Conclusion: The US-based radiomics signature could provide a potential imaging biomarker to accurately predict ESTT malignancy. [ABSTRACT FROM AUTHOR]

Background: In previous studies, the 308‐nm light‐emitting diode (LED) has been proven safe and effective for treating vitiligo. However, direct comparisons between the 308‐nm LED and 308‐nm excimer lamp (308‐nm MEL) for the treatment of vitiligo are lacking. Objective: To compare the efficacy of the 308‐nm LED and 308‐nm MEL for treating nonsegmental stable vitiligo. Patients and Methods: This randomized controlled trial was conducted between January 2018 and August 2023. Enrolled patients were randomly assigned to either the 308‐nm LED or the 308‐nm MEL groups, both receiving 16 treatment sessions. Adverse events that occurred during the treatment were documented. Results: In total, 269 stable vitiligo patches from 174 patients completed the study. A total of 131 lesions were included in the 308‐nm LED group, and 138 lesions were included in the 308‐nm MEL group. After 16 treatment sessions, 38.17% of the vitiligo patches in the 308‐nm LED group achieved repigmentation of at least 50% versus 38.41% in the 308‐nm MEL group. The two devices exhibited similar results in terms of efficacy for a repigmentation of at least 50% (p =.968). The incidence of adverse effects with the two phototherapy devices was comparable (p =.522). Conclusions: Treatment of vitiligo with the 308‐nm LED had a similar efficacy rate to the 308‐nm MEL, and the incidence of adverse effects was comparable between the two devices. [ABSTRACT FROM AUTHOR]

Exposure to ultraviolet radiation can lead to skin photoaging, which increases the risk of skin tumors. This study aims to investigate how microRNA m6A modification contributes to skin photoaging. This study found that skin fibroblasts exposed to a single UVB dose of 30 mJ/cm2 exhibited characteristics of photoaging. The m6A level of total RNA decreased in photoaged cells with a down‐regulated level of METTL14, and overexpression of METTL14 displayed a photoprotective function. Moreover, miR‐100‐3p was a downstream target of METTL14. And METTL14 could affect pri‐miR‐100 processing to mature miR‐100‐3p in an m6A‐dependent manner via DGCR8. Furthermore, miR‐100‐3p targeted at 3′ end untranslated region of ERRFI1 mRNA with an inhibitory effect on translation. Additionally, photoprotective effects of overexpression of METTL14 were reversed by miR‐100‐3p inhibitor or overexpression of ERRFI1. In UVB‐induced photoaging of human skin fibroblasts, METTL14‐dependent m6A can regulate miR‐100‐3p maturation via DGCR8 and affect skin fibroblasts photoaging through miR‐100‐3p/ERRFI1 axis. [ABSTRACT FROM AUTHOR]

Background: Many studies have indicated that negative emotions and personality traits are related to psoriasis, though few have provided causal evidence. Methods: Our analysis utilized 15 genome‐wide association study datasets to identify instrumental variables associated with negative emotions, personality traits and psoriasis vulgaris. Two‐sample Mendelian randomization was conducted to identify the causal associations of negative emotions and personality traits with psoriasis vulgaris. To mitigate bias from multiple tests, we adjusted p‐values using the Benjamini–Hochberg method. Results: Our study revealed causal links between negative emotions and psoriasis vulgaris, including depressed affect, worry too long, feeling hurt, guilty feelings, mood swings, unenthusiasm, miserableness, fed‐up feelings. However, there was no significant evidence of a causal relationship between feeling lonely and psoriasis vulgaris. Additionally, personality traits including neuroticism and openness to experience were found to have causal effects on psoriasis vulgaris. However, no significant evidence supported a causal relationship between agreeableness, conscientiousness, and extraversion with psoriasis vulgaris. Conclusion: Our findings suggest that experiencing negative emotions including depressed affect, worrying excessively, feeling hurt, guilty feelings, mood swings, lack of enthusiasm, miserableness and fed‐up feelings may pose risks for psoriasis vulgaris. Additionally, neuroticism is associated with a risk of psoriasis vulgaris. Conversely, the openness trait may serve a protective role against psoriasis vulgaris. [ABSTRACT FROM AUTHOR]

In real estate valuation using the Hedonic Price Model (HPM) estimated via Ordinary Least Squares (OLS) regression, subjectivity and measurement errors in the independent variables violate the Gauss–Markov theorem assumption of a non-random coefficient matrix, leading to biased parameter estimates and incorrect precision assessments. In this contribution, the Errors-in-Variables model equipped with Total Least Squares (TLS) estimation is proposed to address these issues. It fully considers random errors in both dependent and independent variables. An iterative algorithm is provided, and posterior accuracy estimates are provided to validate its effectiveness. Monte Carlo simulations demonstrate that TLS provides more accurate solutions than OLS, significantly improving the root mean square error by over 70%. Empirical experiments on datasets from Boston and Wuhan further confirm the superior performance of TLS, which consistently yields a higher coefficient of determination and a lower posterior variance factor, which shows its more substantial explanatory power for the data. Moreover, TLS shows comparable or slightly superior performance in terms of prediction accuracy. These results make it a compelling and practical method to enhance the HPM. [ABSTRACT FROM AUTHOR]

The problem of male infertility is a global health crisis and poses a serious threat to the well-being of families. Under heat stress (HS), the reduction of Sertoli cells (SCs) inhibits energy transport and nutrient supply to germ cells, leading to spermatogenesis failure. DNA methylation of genes is a central epigenetic regulatory mechanism in mammalian reproduction. However, it remains unclear how DNA methylation regulates gene expression in heat-stressed SCs. In this study, we investigated whether the decrease in SC levels during HS could be related to epigenetic DNA modifications. The cells exposed to HS showed changes in differential methylation cytosines and regions (DMCs/DMRs) and differential expression genes (DEGs), but not in global DNA methylations. One of the most important biological processes affected by HS is cell apoptosis induced by the intrinsic apoptotic signaling pathway (GO: 2,001,244, P < 0.05) by enrichment in the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The joint analysis showed that several gene expressions in RNA-seq and WGBS overlapped and the shortlisted genes BAX, HSPH1, HSF1B, and BAG were strongly correlated with stress response and apoptosis. Methylation-specific PCR (MSP) and flow cytometry (FCM) analyzes showed that reduced promoter methylation and enhanced gene expression of BAX with a consequence of apoptosis. The activity of BAX, as well as an increase in its expression, is likely to result in a reduction of SCs population which could further impair ATP supply and adversely affect membrane integrity. These findings provide novel insights into the molecular mechanisms through which stressors cause male reproductive dysfunction and a new molecular etiology of male infertility. [ABSTRACT FROM AUTHOR]

In the context of global warming and intensified human activities, glacier instability in plateau regions has increased, and glacier debris flows have become active, which poses a significant threat to the lives and property of people and socioeconomic development. The mass movement process of glacier debris flows is extremely complex, so this paper uses the 2018 Sedongpu glacier debris flow event on the Qinghai-Tibet Plateau as an example and applies a numerical simulation method to invert the whole process of mass movement. In view of the interaction between phases in the process of motion, we use the fluid-solid coupling method to describe the mass movement. The granular-flow model and drift-flux model are employed in FLOW3D software to study the mass movement process of glacier debris flows and explore their dynamic characteristics. The results indicate that the glacier debris flow lasted for 700 s, and the movement process was roughly divided into four stages, including initiation, scraping, surging and deposition; the depositional characteristics calculated by the fluid-solid coupling model are consistent with the actual survey results and have good reliability; strong erosion occurs during the mass movement, the clear volume amplification effect, and the first wave climbs 17.8 m across the slope. The fluid-solid coupling method can better simulate glacier debris flows in plateau regions, which is helpful for the study of the mechanism and dynamic characteristics of such disasters. [ABSTRACT FROM AUTHOR]

Introduction: This study aims to analyze risk factors for ocular surface irritation symptoms in patients with non-corneal-damage inactive mild and moderate-to-severe Graves' orbitopathy (GO). Methods: This retrospective study enrolled 307 patients with non-corneal-damage inactive GO admitted to Sun Yat-sen Memorial Hospital from April 2017 to September 2023. The activity and severity of GO were evaluated using the Clinical Activity Score (CAS) and the European Group on Graves' Orbitopathy (EUGOGO) classification, respectively. Multivariate logistic regression analysis was performed to analyze risk factors for ocular surface irritation symptoms. Results: Among patients with inactive GO, for mild cases, CAS (P < 0.001), upper eyelid lag (P = 0.049), and extraocular muscle involvement (P = 0.019) in the symptomatic group were greater than those in the asymptomatic group, and multivariate logistic regression analysis demonstrated that upper eyelid lag (P = 0.048), CAS 1 (P < 0.001), CAS 2 (P = 0.005), and extraocular muscle involvement (P = 0.029) were risk factors for ocular surface irritation symptoms; for moderate-to-severe cases, CAS (P = 0.004), extraocular muscle involvement (P < 0.001), marginal reflex distance 1 (MRD1) (P = 0.030), and thyroid-stimulating hormone (TSH) (P = 0.034) in the symptomatic group were greater than those in the asymptomatic group, while multivariate logistic regression analysis indicated that extraocular muscle involvement (P = 0.018) and MRD1 (P = 0.012) were risk factors for ocular surface irritation symptoms. Conclusion: In non-corneal-damage inactive mild and moderate-to-severe GO, eyelid malposition and periocular muscle inflammation are risk factors for ocular surface irritation symptoms. Plain Language Summary: Graves' orbitopathy is the most common outward sign of Graves' disease. Patients with inactive Graves' orbitopathy often complain of ocular surface irritation symptoms. This study retrospectively collected clinical data from 307 patients with inactive Graves' orbitopathy and no concurrent corneal damage. The aim was to analyze risk factors for ocular surface irritation symptoms. Upper lid lag, eye movement disorder, and the Clinical Activity Score were found to be risk factors for mild cases. Eye movement disorder and the distance between the upper eyelid margin and corneal reflection point were risk factors for moderate-to-severe cases. To reduce symptoms, it may be helpful to treat inflammation around the eyes and address any eyelid abnormalities. [ABSTRACT FROM AUTHOR]

[Display omitted] • Trop2 played a vital role in metastasis by Trop2/β-catenin positive feedback loop. • Bruceine D inhibited cancer cells proliferation and metastasis by targeting Trop2. • Bruceine D suppressed Trop2-driven ECM-remodeling and EMT to reduce lung metastatic colonization in vivo. • Bruceine D blocked Trop2/β-catenin complex, inducing β-catenin degradation though ubiquitin. Tumor-associated calcium signal transducer 2 (Trop2) has been used as a transport gate for cytotoxic agents into cells in antibody–drug conjugate designs because of its expression in a wide range of solid tumors. However, the specific role of Trop2 itself in breast cancer progression remains unclear and small molecules targeting Trop2 have not yet been reported. To screen small molecules targeting Trop2, and to reveal its pharmacological effects and the molecular mechanisms of action. Small molecule targeting Trop2 was identified by cell membrane chromatography, and validated by cellular thermal shift assay and point mutation analyses. We investigated the pharmacological effects of Trop2 inhibitor using RNA-seq, human foreskin fibroblast (HFF)-derived extracellular matrix (ECM), Matrigel drop invasion assays, colony-forming assay, xenograft tumor model, 4T1 orthotopic metastasis model and 4T1 experimental metastasis model. The molecular mechanism was determined using immunoprecipitation, mass spectrometry, immunofluorescence, immunohistochemistry and Western blotting. Here we identified Bruceine D (BD) as the inhibitor of Trop2, and demonstrated anti-metastasis effects of BD in breast cancer. Notably, Lys307 and Glu310 residues of Trop2 acted as critical sites for BD binding. Mechanistically, BD suppressed Trop2-induced cancer metastasis by blocking the formation of Trop2/β-catenin positive loop, in which the Trop2/β-catenin complex prevented β-catenin from being degraded via the ubiquitin-proteosome pathway. Destabilized β-catenin caused by BD reduced nucleus translocation, leading to the reduction of transcription of Trop2, the reversal of epithelial-mesenchymal transition (EMT) process, and the inhibition of ECM remodeling, further inhibiting cancer metastasis. Additionally, the inhibitory effects of BD on lung metastatic colonization and the beneficial effects of BD on prolongation of survival were validated in 4T1 experimental metastasis model. These results support the tumor-promoting role of Trop2 in breast cancer by stabilizing β-catenin in Trop2/β-catenin positive loop, and suggest Bruceine D as a promising candidate for Trop2 inhibition. [ABSTRACT FROM AUTHOR]

Aims: Breast mucinous cystadenocarcinoma (BMCA) is a rare tumour recently recognised as a distinct entity by the World Health Organisation Tumour Classification Series. BMCA is a triple‐negative tumour that lacks specific immunohistochemical markers; therefore, distinguishing it from mimickers such as ovarian and pancreatic cystadenocarcinomas requires careful clinicopathological correlation. Due to its rarity, little is known about the molecular alterations that underlie BMCA. Methods and results: In this study, we used immunohistochemical staining methods to investigate TRPS1 (trichorhinophalangeal syndrome type 1) expression in BMCA and compare it to expression in ovarian and pancreatic mucinous cystadenocarcinomas. We also collected tumour samples from three BMCA patients for molecular analysis by MALDI‐TOF mass spectrometry, real‐time polymerase chain reaction, whole exome sequencing and fluorescence in‐situ hybridisation. TRPS1 immunoreactivity was found only in BMCA tumour cells and not in the ovarian and pancreatic counterparts. One of the three BMCA tumours also showed a PIK3CA hot‐spot mutation, which was confirmed by whole genome next‐generation sequencing (NGS). No KRAS, NRAS, BRAF or AKT mutations were found. Conclusions: To our knowledge, this is the first demonstration of TRPS1 expression in BMCA patients and the first identification of a PIK3CA hotspot mutation in these tumours. These findings provide insights into the molecular mechanisms underlying BMCA tumorigenesis and suggest a potential drug target for this rare and poorly understood cancer. [ABSTRACT FROM AUTHOR]

Kiwiberry (Actinidia arguta) is a perennial fruit tree belonging to the family Actinidiaceae. Kiwiberries are known to have an extremely high concentration of sugars, phenolics, flavonoids, and vitamin C, and possess delicious taste and health-promoting properties. Numerous studies have focused on kiwiberry fruits, demonstrating that they possess a higher phytochemical content and greater antioxidant activities than other berry fruits. The purpose of this study was to compare the phytochemical content and antioxidant potential of leaf, stem, root, and fruit extracts from twelve kiwiberry cultivars grown in Wonju, Korea, characterized by a Dwa climate (Köppen climate classification). In most kiwiberry cultivars, the total phenolic (TPC) and total flavonoid (TFC) phytochemical content was significantly higher in leaf and stem tissues, while the roots exhibited higher antioxidant activity. In fruit tissues, the TPC and TFC were higher in unripe and ripe kiwiberry fruits, respectively, and antioxidant activity was generally higher in unripe than ripe fruit across most of the cultivars. Based on our results, among the 12 kiwiberry cultivars, cv. Daebo and cv. Saehan have a significantly higher phytochemical content and antioxidant activity in all of the tissue types, thus having potential as a functional food and natural antioxidant. [ABSTRACT FROM AUTHOR]

Background: Recent clinical trials have evaluated the efficacy of vonoprazan‐amoxicillin (VA) dual therapy as the first‐line treatment for Helicobacter pylori infection in different regions with inconsistent results reported. In this systematic review and meta‐analysis, we aimed to evaluate the efficacy of VA dual therapy compared to the currently recommended therapy for eradicating H. pylori. Materials and Methods: A comprehensive search of the PubMed, Cochrane, and Embase databases was performed using the following search terms: ("Helicobacter" OR "H. pylori" OR "Hp") AND ("vonoprazan" OR "potassium‐competitive acid blocker" OR "P‐CAB") AND ("amoxicillin" OR "penicillin") AND ("dual"). The primary outcome was to evaluate the eradication rate according to intention‐to‐treat and per‐protocol analysis. The secondary outcomes were adverse events and compliance. Results: A total of 15 studies involving 4, 568 patients were included. The pooled eradication rate of VA dual therapy was 85.0% and 90.0% by intention‐to‐treat and per‐protocol analysis, respectively. The adverse events rate and compliance of VA dual therapy were 17.5% and 96%, respectively. The efficacy of VA dual therapy was superior to proton pump inhibitors‐based triple therapy (82.0% vs. 71.4%, p < 0.01) but lower than vonoprazan‐containing quadruple therapy (83.1% vs. 93.3%, p = 0.02). 7‐day VA dual therapy showed lower eradication rates than 10‐day (χ2 = 24.09, p < 0.01) and 14‐day VA dual therapy (χ2 = 11.87, p < 0.01). The adverse events rate of VA dual therapy was lower than vonoprazan triple therapy (24.6% vs. 30.9%, p = 0.01) and bismuth‐containing quadruple therapy (20.5% vs. 47.9%, p < 0.01). No significant difference of compliance was observed between VA dual therapy and each subgroup. Conclusion: VA dual therapy, a novel regimen, showed high efficacy as the first‐line treatment for H. pylori eradication, which should be optimized before application in different regions. [ABSTRACT FROM AUTHOR]

Repetitive transcranial magnetic stimulation (rTMS) at left dorsolateral prefrontal cortex (lDLPFC) is commonly used in major depressive disorder (MDD), even though its therapeutic efficacy is limited. Given that many MDD patients show psychomotor retardation, we aim to examine whether the left motor cortex (lMC) as a novel rTMS target would provide effective and well-tolerated treatment as being comparable to lDLPFC-rTMS. In this prospective double-blind randomized single-center study, 131 MDD patients were randomly assigned to the lDLPFC or lMC group and were treated with 10 Hz rTMS (90 % motor threshold) applied twice daily for 4000 pulses continuously over five days. The primary endpoint was the Hamilton Depression Scale (HAMD) total score change after treatment. After the five-day rTMS treatment, there was no significant difference in both HAMD reduction rate (lDLPFC 59.3 % ± 20.4 %, lMC 51.3 % ± 26.3 %, P = 0.10) and adverse effects (P = 0.79) between 48 (73.8 %) lMC subjects and 51 (77.3 %) lDLPFC subjects. Furthermore, the lMC study group showed stable HAMD scores at follow-up compared to their endpoint scores (P = 0.08). Sham-control group was not included and the sample size was small. Therefore, our results should be seen as exploratory and preliminary. The preliminary good therapeutic response, comparability, and tolerability of lMC-rTMS suggest lMC a potential and more easily accessible rTMS target. Together, our findings raise the possibility of symptom-specific rTMS in motor cortex (psychomotor retardation) or lDLPFC (cognitive deficits). This warrants larger clinical trials of rTMS in MDD with symptom-specific stimulation targets. • lMC-rTMS yields a good therapeutic response in MDD patients. • lMC-rTMS shows non-inferior therapeutic effects compared to lDLPFC-rTMS. • lMC-rTMS is well tolerated showing no major side effects. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor T cell (CAR-T) therapy has emerged as a groundbreaking approach in cancer treatment, showcasing remarkable efficacy. However, the formidable challenge lies in taming the formidable side effects associated with this innovative therapy, among which cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS) and on-target off-tumor toxicities (OTOT) are typical representatives. Championing the next frontier in cellular immunotherapy, this comprehensive review embarks on an artistic exploration of leveraging biomaterials to meticulously navigate the intricate landscape of CAR-T cell therapy. Unraveling the tapestry of potential toxicities, our discourse unveils a symphony of innovative strategies designed to elevate the safety profile of this revolutionary therapeutic approach. Through the lens of advanced medical science, we illuminate the promise of biomaterial interventions in sculpting a safer and more efficacious path for CAR-T cell therapy, transcending the boundaries of conventional treatment paradigms. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor T‐cell (CAR‐T) therapy has emerged as a highly efficacious treatment modality for refractory and relapsed hematopoietic malignancies in recent years. Furthermore, CAR technologies for cancer immunotherapy have expanded from CAR‐T to CAR‐natural killer cell (CAR‐NK), CAR‐cytokine‐induced killer cell (CAR‐CIK), and CAR‐macrophage (CAR‐MΦ) therapy. Nevertheless, the high cost and complex manufacturing processes of ex vivo generation of autologous CAR products have hampered broader application. There is an urgent need to develop an efficient and economical paradigm shift for exploring new sourcing strategies and engineering approaches toward generating CAR‐engineered immune cells to benefit cancer patients. Currently, researchers are actively investigating various strategies to optimize the preparation and sourcing of these potent immunotherapeutic agents. In this work, the latest research progress is summarized. Perspectives on the future of CAR‐engineered immune cell manufacturing are provided, and the engineering approaches, and diverse sources used for their development are focused upon. [ABSTRACT FROM AUTHOR]

The lateral confinement effect significantly influences wave amplitude at the generation and propagation stage. A series of physical experiments and numerical simulations considering different parameters was conducted to study the effect of lateral confinement on waves, and the enlargement percentage from lateral confinement on the maximum wave amplitude has been estimated and validated. Results indicate that sliding mass is the most significant factor influencing the wave amplitude on wave generation, with an average influence ratio of 19.0%, and there is a lower influence ratio of 12.3% for particle size parameter. The enlargement percentage induced by lateral confinement decreases from 55.0% to 31.1% on wave generation location as the slide Froude number increases. On the location of wave propagation, the enlargement percentage increases as the slide Froude number increases, ranging from 17.4% to 47.7%. Equations of the enlargement percentage are presented in this study to align the maximum wave amplitude when physical experiments are influenced by lateral confinement. [ABSTRACT FROM AUTHOR]

Owing to high efficacy and safety, natural medicines have found their way into the field of cancer therapy over the past few decades. However, the effective ingredients of natural medicines have shortcomings of poor solubility and low bioavailability. Nanoparticles can not only solve the problems above but also have outstanding targeting ability. Targeting preparations can be classified into three levels, which are target tissues, cells, and organelles. On the premise of clarifying the therapeutic purpose of drugs, one or more targeting methods can be selected to achieve more accurate drug delivery and consequently to improve the anti-tumor effects of drugs and reduce toxicity and side effects. The aim of this review is to summarize the research status of natural medicines' nano-preparations in tumor-targeting therapies to provide some references for further accurate and effective cancer treatments. [ABSTRACT FROM AUTHOR]

In this work, a class of transition metal-modified MCM-41 mesoporous silica supported ionic liquids nanocatalysts were constructed and efficiently used as catalysts for the effective carboxylation of terminal alkynes through CO2 utilization. The main factors affecting the catalytic performance of carboxylation and its possible reaction mechanism were sufficiently discussed. The results showed that when the dosage was 0.2 g, the temperature was 40°C and the CO2 pressure was 0.3 MPa, the supported catalyst MCM-41@IL-Sm showed the optimal catalytic efficiency. The novel catalyst proved to be highly efficient for the sustainable synthesis of alkynyl carboxylic acids attributing good to excellent yields of 82%–95% within 7–12 h. Moreover, MCM-41@IL-Sm could be recycled and reused six times without noticeable decrease in catalytic activity from two-phase system under external heterogeneous field. The application of supported ionic liquids in the field of carbon dioxide carboxylation has injected a new power source for the efficient and effective production of value-added chemicals from waste CO2. [ABSTRACT FROM AUTHOR]

The accumulation of authigenic carbonate in marine sediments has been regarded as a significant contributor to the carbon cycle over Earth's history. However, accurate quantification of the extent of authigenic carbonate formation in both modern and ancient oceans has been challenging due to limited approaches. Here, we analyzed calcium, magnesium, dissolved inorganic carbon, and alkalinity pore‐water profiles of 153 sites influenced by methane diffusion from the northern South China Sea. By combining these data with published data of diffusive sulfate flux, we found a significant positive correlation between carbonate precipitation rate and sulfate flux in the subseafloor. This correlation can be used to quantify the regional extent of authigenic carbonate formation, representing an advantage over a spatial interpolation approach. We therefore propose that the observed correlation can serve as a new approach for quantifying authigenic carbonate formation in shallow sediments along continental margins for both modern and ancient oceans. Plain Language Summary: Carbonate mineral precipitation through removing seawater dissolved inorganic carbon—the marine carbonate factory—plays a critical role in shaping marine carbon cycling and global climate. The formation of authigenic carbonate from pore‐water of marine sediments represents a variable share of the marine carbonate factory throughout geological history. However, it is challenging to quantify the extent of such authigenic carbonate formation. By analyzing pore‐water parameters from 153 sites influenced by methane diffusion of the northern South China Sea, we found a significant positive correlation between the rate of carbonate precipitation and the diffusive flux of sulfate into shallow sediments. Given the existence of estimates on the sizes of the seawater sulfate pool and diffusive fluxes of sulfate into sediments over Earth's history, we propose that the observed correlation can be used for quantifying authigenic carbonate formation in shallow sediments along continental margins through time, which will greatly advance our understanding for past carbon cycling and its relation to climate. Key Points: Porewater parameters from 153 sites of the northern South China Sea were evaluated to quantify the extent of authigenic carbonate formationRate of carbonate formation strongly correlates with diffusive flux of sulfate into sediments affected by methane diffusionA correlation of carbonate formation rate with sulfate flux is used to quantify most of authigenic carbonate formation in shallow sediments [ABSTRACT FROM AUTHOR]

Introduction: With the evolution of radiotherapy techniques and a better understanding of clinicopathological factors, we aimed to evaluate the treatment effect of post-operative radiotherapy (PORT) and associated predictive factors in patients with completely resected pN2 stage III non-small cell lung cancer (R0 pN2-stage III NSCLC). Material and Method: The cancer registration database of a single medical center was searched for R0 pN2-stage III NSCLC. Clinicopathological factors and information about post-operative therapies, including PORT and adjuvant systemic treatment, were retrospectively collected and analyzed. The Kaplan-Meier method and a Cox regression model were applied for time-to-event analysis, with disease-free survival (DFS) being the primary outcome. Results: From 2010 to 2021, 82 R0 pN2-stage III NSCLC patients were evaluated, with 70.1% of tumors harboring epidermal growth factor receptor mutations (EGFR mut.). PORT was performed in 73.2% of cases, and the median dose was 54 Gy. After a median follow-up of 42 months, the 3-year DFS and overall survival (OS) rates were 40.6% and 77.3%, respectively. Distant metastasis (DM) was the main failure pattern. In the overall cohort, DFS was improved with PORT (3-year DFS: 44.9% vs. 29.8%; HR: 0.552, p = 0.045). Positive predictive factors for PORT benefit, including EGFR mut., negative extranodal extension, positive lymphovascular invasion, 1–3 positive lymph nodes, and a positive-to-dissected lymph node ratio ≤0.22, were recognized. OS improvement was also observed in subgroups with less lymph node burden. Conclusions: For R0 pN2-stage III NSCLC, PORT prolongs DFS and OS in selected patients. Further studies on predictive factors and the development of nomograms guiding the application of PORT are highly warranted, aiming to enhance the personalization of lung cancer treatment. [ABSTRACT FROM AUTHOR]

The degradation of Nafion membrane easily occurs after a long run of proton exchange membrane fuel cell. Graphene-oxide (GO) is regarded as an ideal material to form composite membrane. In this work, a multistate empirical valence bond (MS-EVB) method and molecular dynamics method are employed to investigate the effect of GO on transport and solvation characteristics of protons in the degraded hydration membrane. The hydrophilic cluster and its connectivity are analyzed. The interaction between GO, Nafion membrane and water molecules is discussed. The influence of GO on the thermal conduction of Nafion membrane is also evaluated. The results demonstrate that with the addition of GO, the water cluster connectivity of Nafion membrane becomes better. The distribution of hydronium ions and membranes in the water is more uniform, which increases the proton conductivity. The larger GO may not interact well with water molecules, but promotes the thermal conductivity of degraded Nafion membrane more obviously. • MD simulation is conducted for degraded membrane with graphene oxide. • Impact of graphene oxide size on degraded membrane is analyzed. • Influence of graphene oxide on thermal conduction of membrane is evaluated. [ABSTRACT FROM AUTHOR]

In this study, we report a successful strategy for the generation of a type of multifunctional heterogeneous supported ionic liquids catalysts. The synthesized supported ionic liquids (Fe‐MCM‐41/IL) were used in the catalytic cyclocondensation of 2‐aminobenzamide and various ketones and aldehydes towards the efficient synthesis of the dihydroquinazolinones under green conditions. The influence of the different catalysts and reaction parameters on the catalytic behaviors were sufficiently investigated. The supported catalyst (2)Fe‐MCM‐41/IL(0.6) showed the optimal catalytic efficiency. A hot filtration experiment revealed that the reaction proceeded in a heterogeneous pathway. The catalytic activity of (2)Fe‐MCM‐41/IL(0.6) could be maintained efficiently after recycling up to five consecutive runs under the optimized reaction conditions. Merits of this meticulously designed protocol are the use of novel supported catalyst, easy work‐up process, feasibility and sustainability, indicating its potential industrial application prospect. [ABSTRACT FROM AUTHOR]

The dynamic characteristics of the filling body are the key parameters for designing the filling ratio and evaluating the stability of an underground stope. The different environment (water-bearing state) of the filling body in the underground stope exerts a complex impact on the mechanical behavior of the filling body. Therefore, six groups of cemented filling body specimens with different states were formed and subjected to dynamic uniaxial impact tests. The effects of water content on the mechanical properties, fractal dimension, and deformation damage characteristics of the cemented backfill under dynamic load were analyzed in depth, and a dynamic damage constitutive model that considers water damage and the compaction stage was established. The results indicate the following: (1) Due to the change of the specimen from the dry state to the water saturation state, the dynamic compressive strength of the cemented filling body decreases from 5.03 Mpa to 1.79 Mpa; however, the ductility of the specimen generally increases, and the filling body specimens with different water contents mainly exhibit tensile failure. (2) There is a significant nonlinear relationship between the water content and the fractal dimension Db of the cemented backfill specimen, and the growth rate of the fractal dimension Db tends to slow down with the increase in the water content. (3) From the energy evolution perspective, the water content of the specimen exerts a significant effect on the elastic deformation and failure stage of the stress–strain curve, and the slope of the dissipated energy-strain curve decreases with the increase in water content. (4) Based on the Weibull distribution and damage theory, a statistical damage constitutive model of cemented backfill was established, and it was compared with the experimental curve to verify the rationality of the model. Therefore, the relationship between stress and damage and the strain curves is discussed, and it is inferred that the damage evolution curve of cemented backfill is a typical S-shaped curve that exhibits a stable development-rapid increase-tending to be gentle. This study can provide a theoretical reference for further understanding the dynamic behavior and stability of backfill under different water conditions. [ABSTRACT FROM AUTHOR]

A type of MCM-41 supported dual imidazolium ionic liquids have been synthesized and efficiently used as catalysts in the sustainable chemical conversion of CO2 and epoxides into cyclic carbonates. It was shown that the highest efficiency was achieved in the cycloaddition of a variety of epoxides and CO2 in the presence of the MCM-41@DILSCN solid catalyst under mild conditions. More interestingly, the catalyst was stable, very active, robust, and displayed good recyclability without significant loss of catalytic activity after six consecutive cycles during the process. Overall, the present protocol of synthesizing cyclic carbonates under solvent free conditions using MCM-41@DILSCN is promising for industrial applications. [ABSTRACT FROM AUTHOR]

The anisotropic structure of wood will lead to a macroscopic anisotropic property in both mechanical strength and heat transfer. Previous experimental studies of wood materials were mainly focused on the mechanical property while their anisotropic thermal property in different environments is not sufficient. In this research, the anisotropic thermal performance of spruce wood is studied at different temperature, humidity, and mechanical load. The one-dimensional steady-state method and the transient plane source method are adopted to conduct the test. The thermal conductivity in both radial and longitudinal directions of spruce wood at temperature ranging from 25 °C to 422 °C, relative humidity ranging from 30 to 90 % RH, and mechanical load ranging from 0 to 20 MPa are obtained. The accuracy of the TPS method is validated using the 1D steady-state method. Both methods can be utilized to gauge the anisotropic thermal conductivity of spruce wood. Due to the unidirectional distribution of fiber, spruce wood has a longitudinal thermal conductivity that is roughly three times greater than its radial thermal conductivity. Among environmental conditions of temperature, humidity, and mechanical load, the thermal conductivity of spruce wood is varied with temperature more significantly, which is followed by humidity and mechanical load. The measurement uncertainty is also discussed. [ABSTRACT FROM AUTHOR]

Female athletes’ participation in the Olympic Games has increased over the years, however, they are still underrepresented or not covered in global media. Prior literature about gender studies and sport reveals that female athletes were often described through stereotypes, or other linguistic features minimizing their achievements, or focusing on their physical appearance rather than their sports abilities. The present study adopts textual analysis to examine how female athletes were represented during the Beijing 2022 Winter Olympic Games in two Italian leading newspapers. The findings show that there have been positive changes in the portrayal of women in sports, but this may be influenced by the increased nationalism during these mega events. The Italian media are more open to gender equality, and adopt different strategies to describe female athletes, nonetheless, some very limited negative cases are still found. The press tended to emphasize some main themes: female athletes as heroines of the nation, friendship, rivalries and conflicts, and athletes’ private lives. This demonstrates that the Italian newspapers are now more focused on non-sports related stories, to make the articles more interesting in terms of entertainment and emotional stories, to attract more readership. [ABSTRACT FROM AUTHOR]

MoO2/Ni0.2Mo0.8N interfacial nanorods on nickel foam (MONMN-NRs) were reported as an efficient electrocatalyst for the oxygen evolution reaction (OER) in alkaline media. The optimized catalyst delivered an ultralow overpotential of 264 mV@10 mA cm−2 in 1.0 M KOH. The enhanced performance is mainly attributed to the strong electronic interaction between MoO2 and Ni0.2Mo0.8N that facilitates the OER intermediates according to theoretical analysis. [ABSTRACT FROM AUTHOR]

A direct and regioselective lithiation was realized on N‐Boc‐pyrrolo[2,1‐f][1,2,4]triazine, simply utilizing the distinct sigma‐acidity on C‐9. Starting from this enabling discovery, C‐glycoside formation, cyanation, and global deprotection steps constitute one of the most efficient syntheses of GS‐441524. Furthermore, transient protection was applied on GS‐441524 with phenyl boronic acid, which facilitated a powerful one‐pot synthesis of remdesivir. [ABSTRACT FROM AUTHOR]

Given a positive integer M and a real number x ∈ (0 , 1 ] , we call q ∈ (1 , M + 1 ] a univoque simply normal base of x if there exists a unique simply normal sequence (d i) ∈ { 0 , 1 , ... , M } N such that x = ∑ i = 1 ∞ d i q − i. Similarly, a base q ∈ (1 , M + 1 ] is called a univoque irregular base of x if there exists a unique sequence (d i) ∈ { 0 , 1 , ... , M } N such that x = ∑ i = 1 ∞ d i q − i and the sequence (d i) has no digit frequency. Let U S N (x) and U I r (x) be the sets of univoque simply normal bases and univoque irregular bases of x , respectively. In this paper we show that for any x ∈ (0 , 1 ] both U S N (x) and U I r (x) have full Hausdorff dimension. Furthermore, given finitely many rationals x 1 , x 2 , ... , x ℓ ∈ (0 , 1 ] so that each x i has a finite expansion in base M + 1 , we show that there exists a full Hausdorff dimensional set of q ∈ (1 , M + 1 ] such that each x i has a unique expansion in base q. [ABSTRACT FROM AUTHOR]

A series of thioether pleuromutilin derivatives containing 1,2,4‐triazole on the side chain of C14 were designed and synthesized. The in vitro antibacterial activities experiments of the synthesized derivatives showed that compounds 72 and 73 displayed superior in vitro antibacterial effect against MRSA minimal inhibitory concentration (MIC = 0.0625 μg/mL) than tiamulin (MIC = 0.5 μg/mL). The results of time‐kill study and postantibiotic effect study indicated that compound 72 could inhibit the growth of MRSA quickly (−2.16 log10 CFU/mL) and showed certain postantibiotic effect (PAE) time (exposure to 2 × MIC and 4 × MIC for 2 h, the PAE was 1.30 and 1.35 h) against MRSA. Furthermore, the binding mode between compound 72 and 50S ribosome of MRSA was explored by molecular docking and five hydrogen bonds were formed between compound 72 and 50S ribosome. [ABSTRACT FROM AUTHOR]

Background: While current clinically administered anticoagulant medications have demonstrated effectiveness, they have also precipitated significant risks: severe bleeding complications including, but not limited to, gastrointestinal hemorrhaging and intracranial and other life-threatening major bleedings. An ongoing effort is being made to identify the best targets for anticoagulant-targeted drugs. Coagulation factor XIa (FXIa) is emerging as an important target of current anticoagulant treatment. Objective: This review will summarize the development of anticoagulants and recent advances in clinical trials of experimental factor XI inhibitors from a clinical application perspective. Results: As of 1 January 2023, our search screening included 33 clinical trials. We summarized the research progress of FXIa inhibitors from seven clinical trials that evaluated their efficacy and safety. The results showed no statistically meaningful distinction in the primary efficacy between patients receiving FXIa inhibitors compared to controls (RR = 0.796; 95% CI: 0.606–1.046; I2 = 68%). The outcomes did not indicate a statistical difference in the occurrence of any bleeding between patients receiving FXIa inhibitors compared to controls (RR = 0.717; 95% CI: 0.502–1.023; I2 = 60%). A subgroup analysis found significant differences in severe bleeding and clinically relevant hemorrhaging in subjects receiving FXIa inhibitors compared to Enoxaparin (RR = 0.457; 95% CI: 0.256–0.816; I2 = 0%). Conclusions: Clinical trials to date have indicated that factor XIa is a potential anticoagulation target, and factor XIa inhibitors may play an important role in the development of anticoagulants. [ABSTRACT FROM AUTHOR]

Background: To evaluate the role of a standardized first-trimester scan in screening different kinds of central nervous system malformations and to report a 3-year experience from a tertiary center using an unselected cohort. Methods: This was a retrospective analysis of prospectively collected data from a single center evaluating first-trimester scans with predesigned standardized protocols performed between 1 May 2017 and 1 May 2020, involving 39,526 pregnancies. All pregnant women underwent a series of prenatal ultrasound scans at 11–14, 20–24, 28–34 and 34–38 weeks of gestation. Abnormalities were confirmed by magnetic resonance imaging, postmortem examination or trained ultrasound professionals. Pregnancy outcomes and some postnatal follow-up were obtained from maternity medical records and telephone calls. Results: A total of 38,586 pregnancies included in the study. The detection rates of CNS anomalies by ultrasound in the first, second, third and late third trimester were 32%, 22%, 25%, and 16%, respectively. And there were 5% of CNS anomalies missed by prenatal ultrasound. In the first-trimester scan, we diagnosed all cases of exencephaly, anencephaly, alobar holoprosencephaly and meningoencephalocele, and some cases of posterior cranial fossa anomalies (20%), open spina bifida (67%), semilobar holoprosencephaly (75%) and severe ventriculomegaly (8%). Vein of Galen aneurysmal malformation, closed spina bifida, lobar holoprosencephaly, intracranial infection, arachnoid cyst, agenesis of the corpus callosum, cysts of the septum pellucidum and isolated absence of the septum pellucidum were never detected during the first trimester. The abortion rates of fetal CNS anomalies detected by first-trimester scan, second-trimester scan, and third- trimester scan were 96%, 84% and 14%, respectively. Conclusions: The study showed that almost 1/3 of central nervous system anomalies were detected by the standard first-trimester scan and these cases were associated with a high rate of abortion. Early screening for fetal abnormalities gives parents more time for medical advice and safer abortion if needed. It is therefore recommended that some major CNS anomalies should be screened in the first trimester. The standardized anatomical protocol, consisting of four fetal brain planes, were recommended for routine first trimester ultrasound screening. [ABSTRACT FROM AUTHOR]

Although the least-squares (LS) adjustment within the Gauss–Markoff model (GMM) and the model with condition equations as dual problem have been geometrically interpreted, no one merged the LS adjustment formulated by the Gauss–Helmert model (GHM) also into the common pattern. We formulate the GHM from the GMM based on a partial orthogonality between their respective coefficient matrices. Then, the LS adjustment within these three models is interpreted geometrically, which implies that the GHM is not the combined model but the intermediate model between the GMM and the model of conditional equations. Meanwhile, the case of a singular dispersion matrix is analyzed once more, but now in the most general way, where the restriction of the Neitzel–Schaffrin rank condition is relaxed. The findings of this part can be summarized as: (1) The LS solution is developed within the general GHM, which yields the unique best linear uniformly unbiased estimation if the parameter coefficient matrix is of full rank; (2) We demonstrated that Baarda’s S-transformation also holds with the most general model setup; (3) In the general case, we proved that the unique S -homBLUMBE (best homogeneously linear uniformly minimum bias estimation) can be achieved by S - 1 -norm minimization within the LS solution set; (4) The S -homBLE (best homogeneously linear estimation) type is analyzed for the GHM for the first time, and we find it can function as the intermediate algebraic connection between the LS and the S -homBLUMBE solution. [ABSTRACT FROM AUTHOR]

Two series of pleuromutilin derivatives were designed and synthesized as inhibitors against Staphylococcus aureus (S. aureus). 6-chloro-4-amino-1-R-1H-pyrazolo[3,4-d]pyrimidine or 4-(6-chloro-1-R-1H-pyrazolo[3,4-d]pyrimidine-4-yl)amino-phenylthiol were connected to pleuromutilin. A diverse array of substituents was introduced at the N-1 position of the pyrazole ring. The in vitro antibacterial activities of these semisynthetic derivatives were evaluated against two standard strains, Methicillin-resistant Staphylococcus aureus (MRSA) ATCC 43300, Staphylococcus aureus (S. aureus), ATCC 29213 and two clinical S. aureus strains (144, AD3) using the broth dilution method. Compounds 12c, 19c and 22c (MIC = 0.25 μg/mL) manifested good in vitro antibacterial ability against MRSA which was similar to that of tiamulin (MIC = 0.5 μg/mL). Among them, compound 22c killed MRSA in a time-dependent manner and performed faster bactericidal kinetics than tiamulin in time–kill curves. In addition, compound 22c exhibited longer PAE than tiamulin, and showed no significant inhibition on the cell viability of RAW 264.7, Caco-2 and 16-HBE cells at high doses (≤8 μg/mL). The neutropenic murine thigh infection model study revealed that compound 22c displayed more effective in vivo bactericidal activity than tiamulin in reducing MRSA load. The molecular docking studies indicated that compound 22c was successfully localized inside the binding pocket of 50S ribosomal, and four hydrogen bonds played important roles in the binding of them. [ABSTRACT FROM AUTHOR]

Hydrofluoroolefins (HFOs) are a category of environmentally friendly refrigerants. The transport properties such as viscosity and thermal conductivity of pure HFOs and HFO/HFC mixtures are essential for the investigation of flow and heat transfer characteristic of fluids. Therefore, it is necessary to provide the viscosity and thermal conductivity calculation method of HFOs and HFO/HFC mixtures. In this work, the viscosity and thermal conductivity models of HFOs including R1234yf, R1234ze(E), R1234ze(Z), R1243zf, R1336mzz(Z), and R1336mzz(E) were established based on the friction theory (FT) and Peng–Robinson (PR) equation of state, and the overall ARD between the experimental values and those calculated from the model is 1.6% and 2.0%, respectively. The viscosities and thermal conductivities of HFO/HFC mixtures were predicted using mixing rule and the established FT model. Results show that the established FT model has good predictive ability for the viscosity and thermal conductivity of HFO/HFC mixtures. [ABSTRACT FROM AUTHOR]

Key message: Combined GWAS, WGCNA, and gene-based association studies identified the co-expression network and hub genes for maize EC induction. ZmARF23 bound to ZmSAUR15 promoter and regulated its expression, affecting EC induction. Embryonic callus (EC) induction in immature maize embryos shows high genotype dependence, which limits the application of genetic transformation in transgenic breeding and gene function elucidation in maize. Herein, we conducted a genome-wide association mapping (GWAS) for four EC induction-related traits, namely rate of embryonic callus induction (REC), increased callus diameter (ICD), ratio of shoot formation (RSF), and length of shoot (LS) across different environments. A total of 77 SNPs were significantly associated these traits under three environments and using the averages (across environments). Among these significant SNPs, five were simultaneously detected under multiple environments and 11 had respective phenotypic variation explained > 10%. A total of 257 genes were located in the linkage disequilibrium decay of these REC- and ICD-associated SNPs, of which 178 were responsive to EC induction. According to the expression values of the 178 genes, we performed a weighted gene co-expression network analysis (WGCNA) and revealed an EC induction-associated module and five hub genes. Hub gene-based association studies uncovered that the intragenic variations in GRMZM2G105473 and ZmARF23 influenced EC induction efficiency among different maize lines. Dual-luciferase reporter assay indicated that ZmARF23 bound to the promoter of a known causal gene (ZmSAUR15) for EC induction and positively regulated its expression on the transcription level. Our study will deepen the understanding of genetic and molecular mechanisms underlying EC induction and contribute to the use of genetic transformation in maize. [ABSTRACT FROM AUTHOR]

Recognizing facial expressions is crucial for adaptive social interaction. Prior empirical research on facial expression processing has primarily focused on isolated faces; however, facial expressions appear embedded in surrounding scenes in everyday life. In this study, we attempted to demonstrate how the online car‐hailing scene affects the processing of facial expression. This study examined the processing of drivers' facial expressions in scenes by recording event‐related potentials, in which neutral or happy faces embedded in online car‐hailing orders were constructed (with type of vehicle, driver rating, driver surname, and level of reputation controlled). A total of 35 female volunteers participated in this experiment and were asked to judge which facial expressions that emerged in scenes of online car‐hailing were more trustworthy. The results revealed an interaction between facial expression scenes, brain areas, and electrode sites in the late positive potential, which indicated that happy faces elicited larger amplitudes than did neutral ones in the parietal areas and that scenes with happy facial expressions had shorter latencies than did those with neutral ones. As expected, the late positive potential evoked by happy facial expressions in a scene was larger than that evoked by neutral ones, which reflected motivated attention and motivational response processes. This study highlights the importance of scenes as context in the study of facial expression processing. [ABSTRACT FROM AUTHOR]

Duplex stainless steel welded metals were underwater local dry prepared on S32101 lean duplex stainless steel trapezoidal groove plates with a self-made drain cover employing Supercore 2205P flux-cored filler wire. Different heat inputs were employed to investigate the effects on mechanical characteristics and the microstructure of welded metals. The results demonstrated that as the heat was applied, austenite concentrations in the weld metals increased. It was found that the austenite concentration and the fraction of Σ3-austenite twin-grain boundaries followed the same trends. With increasing heat input, the recrystallized ferrite and austenite grains initially decreased and subsequently increased, whereas the fraction of interphase boundaries between special ferrite and austenite exhibited the reverse trend. With a heat input of 1.4 kJ/mm, the toughness and plasticity of the weld metals were enhanced by an increase in austenite content, Σ3 recrystallized grains, and austenite twin-grain boundaries. The plasticity and tensile strength values of the welded metal changed more when the heat input was raised from 1.0 to 1.2 kJ/mm than when it was raised from 1.2 to 1.4 kJ/mm. Considering energy conservation, it is recommended to adopt 1.2 kJ/mm for welding heat input. [ABSTRACT FROM AUTHOR]