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Abstract Background Mesenchymal epithelial transition factor (MET) variant is an independent prognostic factor for worse prognosis in patients with lung cancer or gastroesophageal adenocarcinoma. MET gene variants can be regarded as a subtype of melanoma but there is a lack of studies regarding the frequency of MET genetic alterations and the efficacy of immunotherapy in melanoma patients. The purpose of this study is to explore potential therapeutic strategies for melanoma subtypes with MET alterations. Methods A total of 1751 malignant melanomas were analyzed to illustrate the landscape of MET mutations. We collected 55 melanoma cases from multicenter for a retrospective cohort from 2010 to 2023. We analyzed the impact of MET amplification on the efficacy of immunotherapy in the retrospective cohort after propensity score matching (PSM) and a pancancer cohort. CIBERSORT was used to evaluate the immune infiltration. Results There were no instances of MET 14 exon skipping, and only instances of MET amplification were found in the 1751 melanomas and our retrospective cohort. Cox proportional hazards model analysis showed that MET amplification (P = 0.006) was significantly associated with poorer overall survival (OS) in patients who received immunotherapy as the first-line treatment. Compared with patients with MET amplification, patients in the negative control (NC) group had a significantly better OS (P = 0.022) after PSM. Analysis of 1661 pancancer cases with the MSK-IMPACT assay showed that patients receiving immunotherapy in the MET amplification group had a trend toward worse OS than those without MET amplification (P = 0.025). Conclusions This database analysis showed that the main type of MET mutation is amplification in malignant melanoma. MET-amplified solid tumors might be considered for targeted therapy, as MET amplification can be regarded as a risk factor affecting the prognosis of patients with tumors treated with immunotherapy.

Abstract In clinical nursing, neonatal pain assessment is a challenging task for preventing and controlling the impact of pain on neonatal development. To reduce the adverse effects of repetitive painful treatments during hospitalization on newborns, we propose a novel method (namely pain concept-cognitive computing model, PainC3M) for evaluating facial pain in newborns. In the fusion system, we first improve the attention mechanism of vision transformer by revising the node encoding way, considering the spatial structure, edge and centrality of nodes, and then use its corresponding encoder as a feature extractor to comprehensively extract image features. Second, we introduce a concept-cognitive computing model as a classifier to evaluate the level of pain. Finally, we evaluate our PainC3M on various open pain data sets and a real clinical pain data stream, and the experimental results demonstrate that our PainC3M is very effective for dynamic classification and superior to other comparative models. It also provides a good approach for pain assessment of individuals with aphasia (or dementia).

Abstract During space flight, prolonged weightlessness stress exerts a range of detrimental impacts on the physiology and psychology of astronauts. These manifestations encompass depressive symptoms, anxiety, and impairments in both short-term memory and motor functions, albeit the precise underlying mechanisms remain elusive. Recent studies have revealed that hindlimb unloading (HU) animal models, which simulate space weightlessness, exhibited a disorder in memory and motor function associated with endogenous formaldehyde (FA) accumulation in the hippocampus and cerebellum, disruption of brain extracellular space (ECS), and blockage of interstitial fluid (ISF) drainage. Notably, the impairment of the blood-brain barrier (BBB) caused by space weightlessness elicits the infiltration of albumin and hemoglobin from the blood vessels into the brain ECS. However, excessive FA has the potential to form cross-links between these two proteins and amyloid-beta (Aβ), thereby obstructing ECS and inducing neuron death. Moreover, FA can inhibit N-methyl-D-aspartate (NMDA) currents by crosslinking NR1 and NR2B subunits, thus impairing memory. Additionally, FA has the ability to modulate the levels of certain microRNAs (miRNAs) such as miRNA-29b, which can affect the expression of aquaporin-4 (AQP4) so as to regulate ECS structure and ISF drainage. Especially, the accumulation of FA may inactivate the ataxia telangiectasia-mutated (ATM) protein kinase by forming cross-linking, a process that is associated with ataxia. Hence, this review presents that weightlessness stress-derived FA may potentially serve as a crucial catalyst in the deterioration of memory and motor abilities in the context of microgravity.

Abstract Gestational diabetes mellitus (GDM) is the first spontaneous hyperglycemia during pregnancy. Early diagnosis and intervention are important for the management of the disease. This study compared and analyzed the proteins of total plasma exosomes (T-EXO) and placental-derived exosomes (PLAP-EXO) in pregnant women who subsequently developed GDM (12–16 weeks), GDM patients (24–28 weeks) and their corresponding controls to investigate the pathogenesis and biomarkers of GDM associated with exosomes. The exosomal proteins were extracted and studied by proteomics approach, then bioinformatics analysis was applied to the differentially expressed proteins (DEPs) between the groups. At 12–16 and 24–28 weeks of gestation, 36 and 21 DEPs were identified in T-EXO, while 34 and 20 DEPs were identified in PLAP-EXO between GDM and controls, respectively. These proteins are mainly involved in complement pathways, immunity, inflammation, coagulation and other pathways, most of them have been previously reported as blood or exosomal proteins associated with GDM. The findings suggest that the development of GDM is a progressive process and that early changes promote the development of the disease. Maternal and placental factors play a key role in the pathogenesis of GDM. These proteins especially Hub proteins have the potential to become predictive and diagnostic biomarkers for GDM.

Abstract Objective The present study aimed to investigate the impact of combined use of letrozole in an antagonist protocol during IVF on live birth outcomes and to assess the safety of letrozole in terms of maternal and neonatal complications. Methods This retrospective cohort study included women undergoing IVF/ICSI and fresh embryo transfer (ET) treatment with and without letrozole co-treatment from 2007 to 2021 at Shanghai Ninth People’s Hospital (Shanghai, China). The primary outcome was the live birth rate, while the incidences of maternal and neonatal complications were secondary outcomes. Logistic regression models were used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for the analyzed outcomes. Sensitivity analysis was performed using a propensity score-based patient-matching (PSM) model, an inverse probability weighting (IPW) model, logistic regression models with women undergoing their first IVF-ET cycle, and subgroup analysis. Results Of the 4780 women enrolled in the study, 3887 underwent an antagonist protocol for ovarian stimulation, while 893 received letrozole co-treatment. In this cohort, letrozole co-treatment demonstrated comparable live birth rates to the use of antagonist protocol alone (logistic regression: aOR, 0.88; 95% CI, 0.71–1.08; PSM: aOR, 0.97; 95% CI, 0.77–1.22; IPW: aOR, 0.88; 95% CI, 0.71–1.10). Notably, individuals with a body mass index (BMI) exceeding 24 and those with high ovarian response experienced higher live birth rates under the letrozole co-treatment regimen (BMI ≥ 24: aOR, 1.85; 95% CI, 1.14-3.00; high response: aOR, 1.60; 95% CI, 1.02–2.50). Letrozole co-treatment was also associated with decreased risks of gestational diabetes (aOR, 0.34; 95% CI, 0.15–0.69) and small for gestational age (SGA) fetuses (aOR, 0.42; 95% CI, 0.22–0.75) in fresh ET cycles. These finding were robust in both PSM and IPW models. Conclusions Our findings suggested that letrozole co-treatment in antagonist protocol for IVF/ICSI was associated with a comparable live birth rate following fresh ET. Further prospective randomized studies are needed to verify our results.

Abstract Background Microwave ablation (MWA) is widely used to eliminate colorectal liver metastases (CRLM). However, the risk of tumor recurrence is difficult to predict due to lack of reliable clinical and biological markers. Elevation of gamma-glutamyl transferase (GGT) and aspartate transaminase (AST) provides signals for liver inflammation and cancer progression. The present study evaluated the association between pre-ablation GGT to AST ratio index (GSR) and hepatic recurrence in patients with CRLM after MWA. Methods A retrospectively analyzed 192 CRLM patients who underwent MWA from January 2013 to December 2017. Pre-ablation GSR was classified into high (≤ 2.34) or low (> 2.34) using the upper quartile value. The prognostic value of GSR and other risk factors for liver progression-free survival (LPFS) and cancer-specific survival (CSS) were evaluated by univariate and multivariate analyses. Results High GSR was significantly associated with males (P = 0.041), the presence of cholelithiasis (P = 0.012), but not pre-ablation chemotherapy (P = 0.355), which caused significantly increased levels of GGT (P = 0.015) and AST (P = 0.008). GSR showed a significant association with LPFS and CSS through univariate analysis (P = 0.002 and 0.006) and multivariate analysis (P = 0.043 and 0.037). The subgroup analysis demonstrated no interaction between GSR and all variables except for distribution in the sub-analysis of LPFS. Conclusions Our findings suggest that the pre-ablation GSR can be considered as a promising prognostic indicator for poor prognosis of patients with CRLM underwent MWA. Trial registration Not applicable.

Highlights The energy conversion mechanism is thoroughly analyzed, with a detailed quantitative characterization of the dissipation capacities of polarization, conduction, and magnetic loss. Inspired by DNA transcription, atom and geometry configurations co-modulating multi-scale helical converters achieve the RL min of −63.13 dB at 1.29 mm, and the maximum RCS reduction value reach 36.4 dB m2. Orbital coupling, spin and cross polarization synergize to realize a 6.08 GHz EAB, further expanding to ultrabroad electromagnetic wave absorption of 12.16 GHz through metamaterial design.

Abstract Background Overweight women undergoing IVF treatment have lower success rates. Letrozole, an aromatase inhibitor, has been used as an adjunct for IVF treatment, but its specific effects in overweight women have not been investigated. This study was to explore the effects of letrozole co-treatment in an antagonist protocol for overweight infertile women undergoing IVF treatment. Methods This retrospective cohort study included overweight infertile women who underwent IVF/ICSI treatment and fresh embryo transfer (ET), with or without letrozole co-treatment in an antagonist protocol, from 2007 to 2021 at Shanghai Ninth People’s Hospital (Shanghai, China). A total of 704 overweight infertile women were included: 585 women were in the antagonist group, and 119 women were in the letrozole co-treatment group. The primary outcome was the live birth rate after fresh ET. Propensity score-based patient-matching was employed to balance the covariates between the groups. Multivariate logistic regression analysis was also performed to estimate odds ratio (OR) and 95% confidence interval (CI) for association of letrozole co-treatment and the live birth outcome. Results Letrozole co-treatment induced significant changes in hormonal profile on the trigger day. The letrozole group exhibited a decrease in the total number of follicles compared to the antagonist group, but a higher proportion of large follicles at oocyte retrieval (P 0.05). The letrozole co-treatment group had a significantly higher live birth rate than the control group (38.7% vs. 22.6%, P = 0.026). With multivariate logistic regression analysis, letrozole co-treatment was associated with higher odds of live birth after adjusting for potential confounding factors (adjusted OR = 2.00, 95% CI = 1.17–3.39, P = 0.011). Letrozole presented no significant associations with obstetrical or neonatal complications (P > 0.05). Conclusion Letrozole co-treatment in an antagonist protocol may offer potential benefits for overweight infertile women undergoing IVF treatment. Further research is warranted to validate these findings and explore the broader implications for letrozole co-treatment.

This study was aimed to investigate the effects of dietary calcitriol or quercetin supplementation on eggshell and bone quality of laying hens. In trial 1, 72 Hy-Line Brown layers (80-week-old) with weak-shelled strength (25 to 30 N) were assigned into 4 dietary treatments with 6 replicates of 3 birds and fed a basal diet (4% calcium level) or basal diets supplemented with 0.5% calcium, 5 μg/kg calcitriol or 500 mg/kg quercetin for 4 weeks. In trial 2, 360 Hy-Line Brown layers (60-week-old) were divided into 3 groups with 8 replicates of 15 birds: control group (basal diet), calcitriol group (basal diet + 5 μg/kg calcitriol), and quercetin group (basal diet + 500 mg/kg quercetin). This trial lasted for 12 weeks. The results showed that dietary calcitriol or quercetin improved eggshell quality in both trials (P

Abstract The gap in spectra of a physical system is fundamental in physics, while gap topology further restricts possible occurrent gaps of topological boundary states. The emergence of non-Hermiticity unveils a unique gap type known as the point gap, which forecasts the wavefunction localization, known as the non-Hermitian skin effect. Therefore, experimentally identifying the point gap in the complex frequency plane through a real operating frequency can become a tool for the systematic investigation of skin effects. Here, we utilize a Weyl phononic crystal to demonstrate that the point gap constituted by bulk and Fermi-arc surface states can be observed experimentally by a real-space field mapping technique. The identified point gaps forecast various skin effects and their evolutions. We further experimentally demonstrate the hinge skin effect in a parallelogram structure. Our work provides a feasible recipe to explore point gap topology experimentally in a variety of systems and certainly stimulates the research on skin effects in three-dimensional systems.

Abstract Potato is the most widely grown non-grain crop and ranks as the third most significant global food crop following rice and wheat. Despite its long history of cultivation over vast areas, slow breeding progress and environmental stress have led to a scarcity of high-yielding potato varieties. Enhancing the quality and yield of potato tubers remains the ultimate objective of potato breeding. However, conventional breeding has faced challenges due to tetrasomic inheritance, high genomic heterozygosity, and inbreeding depression. Recent advancements in molecular biology and functional genomic studies of potato have provided valuable insights into the regulatory network of physiological processes and facilitated trait improvement. In this review, we present a summary of identified factors and genes governing potato growth and development, along with progress in potato genomics and the adoption of new breeding technologies for improvement. Additionally, we explore the opportunities and challenges in potato improvement, offering insights into future avenues for potato research.

Abstract Objective To examine the reproductive outcomes of assisted reproductive technology (ART) in gynecologic cancer patients and to assess maternal and neonatal complications. Methods Women diagnosed with gynecologic cancer who underwent their first in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment between 2013 and 2021 at Shanghai Ji Ai Genetics and IVF Institute were included in this study. Infertile women without any history of cancer were matched to the cancer group. The primary outcome was the cumulative live birth rate. Baseline and follow-up data were compared between groups using Student’s t-tests for normally distributed variables and with Chi-square test for categorical variables. A propensity score-based patient-matching approach was adopted to ensure comparability between individuals with and without specific cancer type. Results A total of 136 patients with a history of gynecologic cancer and 241 healthy infertile controls were included in this study. Endometrial cancer constituted 50.70% of the cases and cervical cancer constituted 34.60% of the cases. The cancer group exhibited significantly shorter duration of stimulation, lower levels of estradiol, lower number of retrieved oocytes, day-3 embryos, and blastocysts compared to the control group (P 0.05). The endometrial cancer and cervical cancer groups showed significantly lower cumulative live birth rates than their matched controls (38.60% vs. 64.50%, P = 0.011 and 24.20% vs. 68.60%, P

Abstract Background The global prevalence of autoimmune hepatitis (AIH) is increasing due in part to the lack of effective pharmacotherapies. Growing evidence suggests that fibroblast growth factor 4 (FGF4) is crucial for diverse aspects of liver pathophysiology. However, its role in AIH remains unknown. Therefore, we investigated whether FGF4 can regulate M1 macrophage and thereby help treat liver inflammation in AIH. Methods We obtained transcriptome-sequencing and clinical data for patients with AIH. Mice were injected with concanavalin A to induce experimental autoimmune hepatitis (EAH). The mechanism of action of FGF4 was examined using macrophage cell lines and bone marrow-derived macrophages. Results We observed higher expression of markers associated with M1 and M2 macrophages in patients with AIH than that in individuals without AIH. EAH mice showed greater M1-macrophage polarization than control mice. The expression of M1-macrophage markers correlated positively with FGF4 expression. The loss of hepatic Fgf4 aggravated hepatic inflammation by increasing the abundance of M1 macrophages. In contrast, the pharmacological administration of FGF4 mitigated hepatic inflammation by reducing M1-macrophage levels. The efficacy of FGF4 treatment was compromised following the in vivo clearance of macrophage populations. Mechanistically, FGF4 treatment activated the phosphatidylinositol 3-kinase (PI3K)–protein kinase B (AKT)-signal pathway in macrophages, which led to reduced M1 macrophages and hepatic inflammation. Conclusion We identified FGF4 as a novel M1/M2 macrophage-phenotype regulator that acts through the PI3K–AKT-signaling pathway, suggesting that FGF4 may represent a novel target for treating inflammation in patients with AIH.

This study focuses on addressing housing gaps in populous southern countries by emphasizing the importance of accurate early cost estimation in construction projects. It compares individual cost prediction models (Decision Tree, BP Neural Network, and Support Vector Machine) with combined prediction models (BP-DT and BP-SVM) for high-rise building cost prediction. The study employs interpretative analysis methods such as the Shapley additive explanation method, partial dependence plots, and individual conditional expectation plots to explore feature interplay and improve model transparency. Results show that the BP-SVM combination algorithm significantly reduces Mean Absolute Error (MAE) compared to other models. Key factors influencing cost estimation include “Estimated project duration” and “Ground floor area”, while others like “Below-ground floors” have minimal impact. The study highlights the interaction of various feature groups on prediction outcomes. Through feature interaction analysis, it is found that the Estimated project duration and Building architecture can have some negative correlation interaction. Estimated project duration and Interior decoration may have to cancel effects Overall, it contributes to construction management by aiding investors in better-assessing project profitability, thereby enhancing investment decision efficiency and quality.

AIM:To observe the anti-scarring effects and safety of triamcinolone acetonide(TA)-loaded hydrogel sustained-release sheeting on stab incision glaucoma surgery(SIGS)with “one-step tunnel method” in rabbit eyes.METHODS:A total of 48 healthy New Zealand white rabbits were randomly selected and divided into 4 groups(12 rabbits in each group), trabeculectomy(Trab)group, SIGS group, polyvinyl alcohol hydrogel(PVAH)sheeting was implanted under the conjunctiva flap during SIGS(PVAH group), and hydrogel sustained-release sheeting loaded with TA was implanted under the conjunctiva flap during SIGS(TA/PVAH group). On the 1, 2, 3, and 4 wk after surgery, the intraocular pressure, filtering bubble morphology, anterior chamber reaction, and other complications were observed and recorded in each group. Then animals were euthanized, and the surgery area tissues of right eye were taken for pathological tissue paraffin section. Masson staining, picric acid-Sirius rose red staining, as well as α-smooth muscle actin(α-SMA)and fibroblast growth factor 2(FGF2)immunohistochemistry staining was performed on every section. The infiltration of inflammatory cells, proliferation of fibroblasts and synthesis of type I and type III collagen fibers in local tissues were observed. The average positive area ratio of α-SMA and FGF2 antibody immunohistochemical staining in each group was calculated and compared.RESULTS: The TA/PVAH group maintained diffuse and elevated functional filtering blebs, while flat filtering blebs appeared in Trab, SIGS and PVAH groups at 2 wk after surgery. Functional filtering blebs were present in 1 eye(33%), 2 eyes(67%)in the PVAH and TA/PVAH group at 4 wk after surgery, respectively, while the other filtering blebs were flattened. Masson staining showed that the hydrogels in PVAH and TA/PVAH groups did not degrade at 4 wk after surgery. Compared with the Trab and SIGS groups, the filtration passages were more obvious, with less collagen fiber proliferation. Sirius red staining showed that the expression of type I collagen and type III collagen in the TA/PVAH group was less than that in the Trab group, SIGS group and PVAH group at 4 wk after surgery. Immunohistochemical staining showed that the α-SMA expression in the TA/PVAH group was significantly lower than that in the Trab and SIGS groups at 1 wk after surgery(P

Spillover effect refers to the phenomenon that when an economic entity, industry or market encounters a change or shock, its impact is transmitted to other entities, industries or markets. In recent years, 5G, semiconductors and rare earths have successively become geopolitical battlegrounds. In this paper, sparrow search algorithm was used to optimize the parameters of variational mode decomposition (VMD), then use the optimized VMD to decompose the geopolitical risk (GPR), 5G, semiconductor and rare earth time series data, and exploit fuzzy c-means clustering algorithm to obtain low-frequency and high-frequency time series. Finally we investigated the connectedness between GPR and China's 5G, semiconductor, and rare earth industries based on TVP-VAR model in different cycles, as well as between these industries. The findings reveal that there exists risk spillover between GPR and the three industries, which is significantly enhanced under the impact of geopolitical events. In addition, there is heterogeneity in the risk spillover between GPR and these three industries in different cycles. Notably, in the short term, the GPR is the main source of risk, and in the long term, the semiconductor industry has the great impact on GPR, 5G and rare earth industries, indicating that the semiconductor industry has very important geopolitical significance.

Abstract De novo lipogenesis (DNL), a hallmark of cancer, facilitates tumor growth and metastasis. Therapeutic drugs targeting DNL are being developed. However, how DNL is directly regulated in cancer remains largely unknown. Here, transcription factor sine oculis homeobox 1 (SIX1) is shown to directly increase the expression of DNL‐related genes, including ATP citrate lyase (ACLY), fatty acid synthase (FASN), and stearoyl‐CoA desaturase 1 (SCD1), via histone acetyltransferases amplified in breast cancer 1 (AIB1) and lysine acetyltransferase 7 （HBO1/KAT7）, thus promoting lipogenesis. SIX1 expression is regulated by insulin/lncRNA DGUOK‐AS1/microRNA‐145‐5p axis, which also modulates DNL‐related gene expression as well as DNL. The DGUOK‐AS1/microRNA‐145‐5p/SIX1 axis regulates liver cancer cell proliferation, invasion, and metastasis in vitro and in vivo. In patients with liver cancer, SIX1 expression is positively correlated with DGUOK‐AS1 and SCD1 expression and is negatively correlated with microRNA‐145‐5p expression. DGUOK‐AS1 is a good predictor of prognosis. Thus, the DGUOK‐AS1/microRNA‐145‐5p/SIX1 axis strongly links DNL to tumor growth and metastasis and may become an avenue for liver cancer therapeutic intervention.

High‐entropy materials have drawn much attention as battery materials due to their distinctive properties. Lithiated high‐entropy oxide (Li0.33(MgCoNiCuZn)0.67O, LiHEO) exhibits both high lithium‐ion and electronic conductivity, making it a potential coating material for layered Ni‐rich oxide cathodes (Li1+x(Ni1−y−zCoyMnz)1−xO2, NCM or NMC) in conventional Li‐ion battery cells; however, high‐temperature synthesis limits its application. Therefore, a photonic curing strategy is used for synthesizing LiHEO and the non‐lithiated form (denoted as high‐entropy oxide [HEO]), and nanoscale coatings are successfully produced on LiNi0.85Co0.1Mn0.05O2 (NCM851005) particles. To one's knowledge, this is the first report on particle coating with high‐entropy materials using photonic curing. NCM851005 with LiHEO‐modified surface shows good cycling stability, with a capacity retention of 97% at 1 C rate after 200 cycles. The improvement in electrochemical performance is attributed to the conformal coating that prevents structural changes caused by the reaction between cathode material and liquid electrolyte. Compared to bare NCM851005, the coated material shows a significantly reduced tendency for intergranular cracking, successfully preventing electrolyte penetration and suppressing side reactions. Overall, photonic curing presents a novel cost‐ and energy‐efficient synthesis and coating procedure that paves the way for surface modification of any heat‐sensitive material for a wide range of applications.

Oceans are repositories of radionuclides. Radionuclides are transferred through the food chain and cause ionizing radiation hazards for marine organisms. In this study, the transfer characteristics of 226Ra, 40K, 14C, 3H, 137Cs and 90Sr in organisms at different trophic levels in the eastern coast of Yantai city were investigated. The risk of ionizing radiation to organisms was assessed using the ERICA Tool 2.0. The results show no significant changes in the concentration of any of the nuclides in the coastal area compared to the preoperation period of the nuclear power plant. The transfer factor of 137Cs, 40K, 226Ra, 14C, 90Sr and 3H at the different trophic levels of marine organisms were 2.09, 1.29, 1.17, 1.15, 1.06 and 0.74, respectively. The dose rates of ionizing radiation to organisms from six radionuclides ranged from 32.02 nGy·h-1 to 195.49 nGy·h-1 and had a mean value of 102.86 ± 57.30 nGy·h-1. The main artificial radionuclides (14C, 3H, 90Sr, 137Cs) released by nuclear power plants in the study area produced negligible radiation doses to marine organisms. However, other artificial radionuclides present in the effluents of nuclear power plants (99Tc, 110mAg and 131I) as well as other natural radionuclides (includes 210Po, 210Pb, etc) were not included, and further evaluation of these is recommended.

G protein-coupled receptors (GPCRs), widely expressed in the human central nervous system (CNS), perform numerous physiological functions and play a significant role in the pathogenesis of diseases. Consequently, identifying key therapeutic GPCRs targets for CNS-related diseases is garnering immense interest in research labs and pharmaceutical companies. However, using GPCRs drugs for treating neurodegenerative diseases has limitations, including side effects and uncertain effective time frame. Recognizing the rich history of herbal treatments for neurological disorders like stroke, Alzheimer's disease (AD), and Parkinson's disease (PD), modern pharmacological research is now focusing on the understanding of the efficacy of traditional Chinese medicinal herbs and compounds in modulating GPCRs and treatment of neurodegenerative conditions. This paper will offer a comprehensive, critical review of how certain natural products and compounds target GPCRs to treat neurological diseases. Conducting an in-depth study of herbal remedies and their efficacies against CNS-related disorders through GPCRs targeting will augment our strategies for treating neurological disorders. This will not only broaden our understanding of effective therapeutic methodologies but also identify the root causes of altered GPCRs signaling in the context of pathophysiological mechanisms in neurological diseases. Moreover, it would be informative for the creation of safer and more effective GPCR-mediated drugs, thereby establishing a foundation for future treatment of various neurological diseases.

Social–emotional competencies, a crucial non-academic factor for K-12 students to be competent 21st century citizens, are receiving increasing research attention. Based on the 2,801 self-reports of grades 4–8 students from four schools in China, this study scrutinized the associations between adolescents’ five core competencies and their interpersonal relationships. Results indicated that five competencies acted as mediators between parent–child relationships and students’ relationships with teachers and peers. In addition to the girls’ advantage in five competencies, the results also demonstrated the gender and grade differences in the association. Boys had more indirect links and girls had both direct and indirect associations. There were grade differences in the mediating role of social awareness. The study’s findings may advance our understanding of the parental influence on Chinese students’ social–emotional competencies and provide a more nuanced picture of the conditions and interplay that foster or hinder students’ proficiency in these competencies in schools and families.

Abstract Metal‐organic frameworks (MOFs), renowned for structural diversity and design flexibility, exhibit potential in catalysis. However, the pursuit of higher catalytic activity through defects often compromises stability, requiring a delicate balance. Traditional trial‐and‐error method for optimizing synthesis parameters within the complex chemical space is inefficient. Herein, taking the typical MOF UiO‐66(Ce) as an illustrative example, a closed loop workflow is built, which integrates machine learning (ML)‐assissted prediction, multi‐objective optimization (MOO) and experimental preparation to synergistically optimize the defect content and thermal stability of UiO‐66(Ce) for efficient hydrogenation of dicyclopentadiene (DCPD). An automatic data extraction program ensures data accuracy, establishing a high‐quality database. ML is employed to explore the intricate synthesis‐structure‐property correlations, enabling precise delineation of pure‐phase subspace and accurate predictions of properties. After two iterations, MOO model identifies optimal protocols for high defect content (>40%) and thermal stability (>300°C). The optimized UiO‐66(Ce) exhibits superior catalytic performance in hydrogenation of DCPD, validating the precision and reliability of our methodology. This ML‐assisted approach offers a valuable paradigm for solving the trade‐off riddle in materials field.

Abstract Due to its outstanding physical and chemical properties, graphene synthesized by laser scribing on polyimide (PI) offers excellent opportunities for photothermal applications, antiviral and antibacterial surfaces, and electrochemical storage and sensing. However, the utilization of such graphene for imaging is yet to be explored. Herein, using chemically durable and electrically conductive laser‐induced graphene (LIG) for tomography imaging in aqueous suspensions is proposed. These graphene electrodes are designed as impedance imaging units for four‐terminal electrical measurements. Using the real‐time portable imaging prototypes, the conductive and dielectric objects can be seen in clear and muddy water with equivalent impedance modeling. This low‐cost graphene tomography measurement system offers significant advantages over traditional visual cameras, in which the suspended muddy particles hinder the imaging resolution. This research shows the potential of applying graphene nanomaterials in emerging marine technologies, such as underwater robotics and automatic fisheries.

IntroductionNK cells are dysfunctional in myasthenia gravis (MG), but the mechanism is unclear. This study aims to measure associations and underlying mechanisms between the NK cells and the development of MG.MethodsTwenty healthy controls (HCs) and 53 MG patients who did not receive glucocorticoids and immunosuppressants were collected. According to the Myasthenia Gravis Foundation of America (MGFA) classification, MG patients were categorized into MGFA I group (n = 18) and MGFA II-IV group (n = 35). Flow cytometry, cell sorting, ELISA, mRNA-sequencing, RT-qPCR, western blot, and cell culture experiments were performed to evaluate the regulatory mechanism of exhausted NK cells.ResultsPeripheral NK cells in MGFA II-IV patients exhibit exhausted phenotypes than HCs, marked by the dramatic loss of total NK cells, CD56dimCD16− NK cells, elevated PD1 expression, reduced NKG2D expression, impaired cytotoxic activity (perforin, granzyme B, CD107a) and cytokine secretion (IFN-γ). Plasma IL-6 and IL-21 are elevated in MG patients and mainly derived from the aberrant expansion of monocytes and Tfh cells, respectively. IL-6/IL-21 cooperatively induced NK-cell exhausted signature via upregulating SOCS2 and inhibiting the phosphorylation of STAT5. SOCS2 siRNA and IL-2 supplement attenuated the IL-6/IL-21-mediated alteration of NK-cell phenotypes and function.DiscussionInhibition of IL-6/IL-21/SOCS2/STAT5 pathway and recovery of NK-cell ability to inhibit autoimmunity may be a new direction in the treatment of MG.

Fibroblast activation and extracellular matrix (ECM) deposition play an important role in the tracheal abnormal repair process and fibrosis. As a transcription factor, SOX9 is involved in fibroblast activation and ECM deposition. However, the mechanism of how SOX9 regulates fibrosis after tracheal injury remains unclear. We investigated the role of SOX9 in TGF-β1-induced fibroblast activation and ECM deposition in rat tracheal fibroblast (RTF) cells. SOX9 overexpression adenovirus (Ad-SOX9) and siRNA were transfected into RTF cells. We found that SOX9 expression was up-regulated in RTF cells treated with TGF-β1. SOX9 overexpression activated fibroblasts and promoted ECM deposition. Silencing SOX9 inhibited cell proliferation, migration, and ECM deposition, induced G2 arrest, and increased apoptosis in RTF cells. RNA-seq and chromatin immunoprecipitation sequencing (ChIP-seq) assays identified MMP10, a matrix metalloproteinase involved in ECM deposition, as a direct target of SOX9, which promotes ECM degradation by increasing MMP10 expression through the Wnt/β-catenin signaling pathway. Furthermore, in vivo, SOX9 knockdown ameliorated granulation proliferation and tracheal fibrosis, as manifested by reduced tracheal stenosis. In conclusion, our findings indicate that SOX9 can drive fibroblast activation, cell proliferation, and apoptosis resistance in tracheal fibrosis via the Wnt/β-catenin signaling pathway. The SOX9–MMP10–ECM biosynthesis axis plays an important role in tracheal injury and repair. Targeting SOX9 and its downstream target MMP10 may represent a promising therapeutic approach for tracheal fibrosis.

One-third of patients with autoimmune hepatitis (AIH) have cirrhosis at the time of diagnosis. The relevance of these variables, although unknown, is believed to be critical in AIH because of suspected interactions between the gut microbiome and genetic factors. Dysbiosis of the gut flora and elevated polymeric immunoglobulin receptor (pIgR) levels have been observed in both patients and mouse models. Moreover, there is a direct relationship between pIgR expression and transaminase levels in patients with AIH. In this study, we aimed to explore how pIgR influences the secretion of regenerating islet-derived 3 beta (Reg3b) and the flora composition in AIH using in vivo experiments involving patients with AIH and a concanavalin A-induced mouse model of AIH. Reg3b expression was reduced in pIgR gene (Pigr)-knockout mice compared to that in wild-type mice, leading to increased microbiota disruption. Conversely, exogenous pIgR supplementation increased Reg3b expression and maintained microbiota homeostasis. RNA sequencing revealed the participation of the interleukin (IL)-17 signaling pathway in the regulation of Reg3b through pIgR. Furthermore, the introduction of external pIgR could not restore the imbalance in gut microbiota in AIH, and the decrease in Reg3b expression was not apparent following the inhibition of signal transducer and activator of transcription 3 (STAT3). In this study, pIgR facilitated the upregulation of Reg3b via the STAT3 pathway, which plays a crucial role in preserving the balance of the intestinal microbiota in AIH. Through this research, we discovered new molecular targets that can be used for the diagnosis and treatment of AIH.

Highly efficient thermal management of electronic devices has grown in significance with the burgeoning of semiconductor technology and 5th generation communication. It is urgently desired to rationally construct highly thermally conductive composite films for enhancing the performance, service life and operation reliability of electronic equipment. Aramid nanofibers (ANFs), as one of the most promising building blocks to fabricate high-performance and multifunctional composite films, have attracted wide attention of researchers over the past few years due to its impressive mechanical performances, excellent electric insulation, and outstanding thermal stability. Especially, the rational assembly of ANFs with low-dimensional thermally conductive nanofillers exhibits significant opportunity for developing highly thermally conductive flexible composite films. However, there is no specialized review to systematically summarize the research advances and prospective challenges of this area until now. Herein, the preparation strategies, structure and properties, as well as the potential applications of various ANFs-based thermally conductive composite films with different low-dimensional nanofillers are highlighted. Finally, possible challenges and opportunities for ANFs-based thermally conductive composite films are envisioned. This brief review delivers the readers an in-depth understanding of the thermal conduction performances of ANFs-based composite films, which may give meaningful enlightenment for designing advanced thermal management materials and ANFs-based functional composites.

Abstract Purpose To use artificial intelligence to establish an automatic diagnosis system for corneal endothelium diseases (CEDs). Methods We develop an automatic system for detecting multiple common CEDs involving an enhanced compact convolutional transformer (ECCT). Specifically, we introduce a cross-head relative position encoding scheme into a standard self-attention module to capture contextual information among different regions and employ a token-attention feed-forward network to place greater focus on valuable abnormal regions. Results A total of 2723 images from CED patients are used to train our system. It achieves an accuracy of 89.53%, and the area under the receiver operating characteristic curve (AUC) is 0.958 (95% CI 0.943–0.971) on images from multiple centres. Conclusions Our system is the first artificial intelligence-based system for diagnosing CEDs worldwide. Images can be uploaded to a specified website, and automatic diagnoses can be obtained; this system can be particularly helpful under pandemic conditions, such as those seen during the recent COVID-19 pandemic.

Abstract Background Anthraquinone-fused enediynes (AFEs) are excellent payloads for antibody-drug conjugates (ADCs). The yields of AFEs in the original bacterial hosts are extremely low. Multiple traditional methods had been adopted to enhance the production of the AFEs. Despite these efforts, the production titers of these compounds are still low, presenting a practical challenge for their development. Tiancimycins (TNMs) are a class of AFEs produced by Streptomyces sp. CB03234. One of their salient features is that they exhibit rapid and complete cell killing ability against various cancer cell lines. Results In this study, a combinatorial metabolic engineering strategy guided by the CB03234-S genome and transcriptome was employed to improve the titers of TNMs. First, re-sequencing of CB03234-S (Ribosome engineered mutant strains) genome revealed the deletion of a 583-kb DNA fragment, accounting for about 7.5% of its genome. Second, by individual or combined inactivation of seven potential precursor competitive biosynthetic gene clusters (BGCs) in CB03234-S, a double-BGC inactivation mutant, S1009, was identified with an improved TNMs titer of 28.2 ± 0.8 mg/L. Third, overexpression of five essential biosynthetic genes, including two post-modification genes, and three self-resistance auxiliary genes, was also conducted, through which we discovered that mutants carrying the core genes, tnmE or tnmE10, exhibited enhanced TNMs production. The average TNMs yield reached 43.5 ± 2.4 mg/L in a 30-L fermenter, representing an approximately 360% increase over CB03234-S and the highest titer among all AFEs to date. Moreover, the resulting mutant produced TNM-W, a unique TNM derivative with a double bond instead of a common ethylene oxide moiety. Preliminary studies suggested that TNM-W was probably converted from TNM-A by both TnmE and TnmE10. Conclusions Based on the genome and transcriptome analyses, we adopted a combined metabolic engineering strategy for precursor enrichment and biosynthetic pathway reorganization to construct a high-yield strain of TNMs based on CB03234-S. Our study establishes a solid basis for the clinical development of AFE-based ADCs.

Abstract Background Immunosuppression is a leading cause of septic death. Therefore, it is necessary to search for biomarkers that can evaluate the immune status of patients with sepsis. We assessed the diagnostic and prognostic value of low-density neutrophils (LDNs) and myeloid-derived suppressor cells (MDSCs) subsets in the peripheral blood mononuclear cells (PBMCs) of patients with sepsis. Methods LDNs and MDSC subsets were compared among 52 inpatients with sepsis, 33 inpatients with infection, and 32 healthy controls to investigate their potential as immune indicators of sepsis. The percentages of LDNs, monocytic MDSCs (M-MDSCs), and polymorphonuclear MDSCs (PMN-MDSCs) in PBMCs were analyzed. Sequential organ failure assessment (SOFA) scores, C-reactive protein (CRP), and procalcitonin (PCT) levels were measured concurrently. Results The percentages of LDNs and MDSC subsets were significantly increased in infection and sepsis as compared to control. MDSCs performed similarly to CRP and PCT in diagnosing infection or sepsis. LDNs and MDSC subsets positively correlated with PCT and CRP levels and showed an upward trend with the number of dysfunctional organs and SOFA score. Non-survivors had elevated M-MDSCs compared with that of patients who survived sepsis within 28 days after enrollment. Conclusions MDSCs show potential as a diagnostic biomarker comparable to CRP and PCT, in infection and sepsis, even in distinguishing sepsis from infection. M-MDSCs show potential as a prognostic biomarker of sepsis and may be useful to predict 28-day hospital mortality in patients with sepsis.

Objective The karst area in southwestern China is one of the three concentrated karst distribution areas in the world. Karst groundwater is highly susceptible to pollution from the surface due to the unique structure of aquifers. Methods To investigate the dominant factors influencing the spatial distribution of antibiotic pollution, clarify the correlation between antibiotics and hydrochemical parameters, and then identify the indicators of antibiotic pollution in karst groundwater systems, a typical karst groundwater system in southwestern China was selected as the research object. Thirty-five antibiotics were analysed using ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Results The results showed that a total of thirty antibiotics were detected in the study area, including 3 tetracyclines (< MDL -421 ng/L), 5 macrolides (28.3-884 ng/L), 9 sulfonamides (2.50-30 ng/L) and 13 quinolones (19.5-1 807 ng/L).Among them, macrolides and quinolones were the dominant antibiotics in the study area, whose spatial distribution was dominated by pollution sources and dilution effects. The results of Pearson correlation analysis showed that the concentrations of inorganic nitrogen (the sum of NH4+-N, NO2--N and NO3--N), total organic carbon (TOC), Na+ and Cl- were significantly positively correlated with the concentration of individual antibiotics, the concentration of various antibiotic species, and the total concentration of antibiotics (r=0.81-0.99, p < 0.05, N=7-8). With more stable properties than inorganic nitrogen, TOC and Na+, Cl- is a more reliable indicator of antibiotic pollution in groundwater in karst areas. Conclusion This study provides a theoretical basis for the identification and prediction of antibiotic pollution in karst areas affected by county-level wastewater treatment plants (WWTPs) and rural domestic wastewater discharges.

Abstract Objective Progressive infarction (PI) has a negative effect on functional prognosis. Our study aimed to develop and validate a risk score for predicting PI in patients with anterior circulation single subcortical infarction (ACSSI). Methods Between January 2020 and October 2022, we retrospectively enrolled 638 eligible patients with ACSSI. Two‐thirds of the eligible patients were randomly allocated to the training cohort (n = 425). Another resampling sample was formed through the bootstrap method and was used as the validation group (n = 425). Multivariate logistic regression analysis was used to identify the independent factors associated with PI. Each factor was then point assigned based on β‐coefficient and a risk scoring system was developed. This scoring system was internally validated through 1000‐bootstrap resamplings. The C‐statistic and Hosmer‐Lemeshow test were used to assess model discrimination and calibration. Results PI occurred in 121 patients, accounting for 19.0% of the total patients. A 7‐point NTS score system based on the initial NIHSS score, triglyceride‐glucose index, and the number of infarct slices on axial diffusion‐weighted imaging was developed. The NTS score showed good discrimination and calibration in the training cohort (C‐statistic = 0.686; p value of Hosmer–Lemeshow test = 0.797) and validation cohort (C‐statistic = 0.681; p value of Hosmer–Lemeshow test = 0.451). The three risk levels for predicting PI in the training and validation cohorts based on NTS score were as follows: low (0–2, 9.6% vs. 9.3%), intermediate (3–5, 28.2% vs. 26.7%), and high risk (6–7, 60.2% vs. 57.4%). Interpretation The NTS score is a valid and convenient risk score for predicting PI in ACSSI patients.

Abstract Background The causality of the relationship between bronchiectasis and chronic obstructive pulmonary disease (COPD) remains unclear. This study aims to investigate the potential causal relationship between them, with a specific focus on the role of airway inflammation, infections, smoking as the mediators in the development of COPD. Methods We conducted a two-sample Mendelian randomization (MR) analysis to assess: (1) the causal impact of bronchiectasis on COPD, sex, smoking status, infections, eosinophil and neutrophil counts, as well as the causal impact of COPD on bronchiectasis; (2) the causal effect of smoking status, infections and neutrophil counts on COPD; and (3) the extent to which the smoking status, infections and neutrophil counts might mediate any influence of bronchiectasis on the development of COPD. Results COPD was associated with a higher risk of bronchiectasis (OR 1.28 [95% CI 1.05, 1.56]). Bronchiectasis was associated with a higher risk of COPD (OR 1.08 [95% CI 1.04, 1.13]), higher levels of neutrophil (OR 1.01 [95% CI 1.00, 1.01]), higher risk of respiratory infections (OR 1.04 [95% CI 1.02, 1.06]) and lower risk of smoking. The causal associations of higher neutrophil cells, respiratory infections and smoking with higher COPD risk remained after performing sensitivity analyses that considered different models of horizontal pleiotropy, with OR 1.17, 1.69 and 95.13, respectively. The bronchiectasis–COPD effect was 0.99, 0.85 and 122.79 with genetic adjustment for neutrophils, respiratory infections and smoking. Conclusion COPD and bronchiectasis are mutually causal. And increased neutrophil cell count and respiratory infections appears to mediate much of the effect of bronchiectasis on COPD.

Abstract Background Vancomycin-associated acute kidney injury (VA-AKI) is the most clinically relevant side effect of vancomycin. The objective of this study was to investigate the association between VTC and VA-AKI as well as 30-day mortality in critically ill elderly adults. Method Elderly patients with trough serum vancomycin concentration records(VTC) in the Medical Information Mart-IV (MIMIC-IV) and eICU databases were retrospectively studied. Results A total of 3,146 critically ill elderly adults were finally enrolled. The incidence of VA-AKI in the elderly population was 76.5%. Logistic regression analysis revealed significant relationships between VA-AKI and various factors, including VTC, comorbidities, and laboratory indicators, and SOFA, and GCS score. For each mg/L increase, the OR for VA-AKI increased by 2.5%. The association between VTC and 30-day mortality was found to be statistically significant (odds ratio (OR): 1.021, 95% CI: 1.010–1.031), P 6, patients with baseline creatinine > 1.2 mg/dl and patients with or without exposed to other nephrotoxic medications. Conclusion This study found the significant association between VTC and the incidence of VA-AKI and 30-day mortality in critically ill elderly adults. The RCS curves indicated concentration ranges for AKI (19.67–35.72 mg/L) and 30-day mortality (19.17–42.86 mg/L), signifying increased risk.

Background Research on food addiction has increased significantly in recent years. It has been demonstrated that food addiction can lead to impairments in physiological, psychological, and social functioning in individuals. However, there is a lack of studies investigating the influence of how individuals handle social situations on food addiction and the specific mechanisms involved. Method A cross-sectional survey was conducted with 1,151 university students, with a mean age of 21.44 (SD = 4.77) years. The sample comprised 74.46% female and 25.54% male students. Participants completed the Chinese version of the modified Yale Food Addiction Scale 2.0, the Social Physique Anxiety Scale, the Expressive Suppression Scale, and the Social Avoidance and Distress Scale. Statistical analyses were performed using SPSS 26.0 and the Process (Version 3.4) plug-in. Result The results of the study supported our hypothesis that the association between social physique anxiety and food addiction symptoms could be partially explained by expressive suppression and social avoidance and distress. This association remained significant even after adjusting for covariates such as gender, number of cigarettes smoked per day, bedtime, education, and BMI. Specifically, more severe social physique anxiety was found to be associated with frequent use of expressive suppression and social avoidance and distress, which in turn was associated with more severe food addiction symptoms. Conclusion This study explored the role of expression suppression and social avoidance and distress in the relationship between social physique anxiety and food addiction symptoms. The findings provide a theoretical basis for developing interventions for food addiction in college students. These interventions could include helping students develop a healthy perception of body image, encouraging emotional expression, and promoting active social participation to reduce food addiction symptoms.

Hadal zones account for the deepest 45% of the oceanic depth range and play an important role in ocean biogeochemical cycles. As the least-explored aquatic habitat on earth, hadal ecosystems contain a vast diversity of so far uncultured microorganisms that cannot be grown on conventional laboratory culture media. Therefore, it has been difficult to gain a true understanding of the detailed metabolic characteristics and ecological functions of those difficult-to-culture microorganisms in hadal environments. In this study, a novel anaerobic bacterial strain, MT110T, was isolated from a hadal sediment–water interface sample of the Mariana Trench at 10,890 m. The level of 16S rRNA gene sequence similarity and percentage of conserved proteins between strain MT110T and the closest relatives, Anaerovorax odorimutans DSM 5092T (94.9 and 46.6%) and Aminipila butyrica DSM 103574T (94.4 and 46.7%), indicated that strain MT110T exhibits sufficient molecular differences for genus-level delineation. Phylogenetic analyses based on both 16S rRNA gene and genome sequences showed that strain MT110T formed an independent monophyletic branch within the family Anaerovoracaceae. The combined evidence showed that strain MT110T represents a novel species of a novel genus, proposed as Anoxybacterium hadale gen. nov. sp. nov. (type strain MT110T = KCTC 15922T = MCCC 1K04061T), which represents a previously uncultured lineage of the class Clostridia. Physiologically, no tested organic matter could be used as sole carbon source by strain MT110T. Genomic analysis showed that MT110T had the potential capacity of utilizing various carbon sources, but the pathways of sulfur reduction were largely incomplete. Our experiments further revealed that cysteine is one of the essential nutrients for the survival of strain MT110T, and cannot be replaced by sulfite, leucine, or taurine. This result suggests that organic sulfur compounds might play an important role in metabolism and growth of the family Anaerovoracaceae and could be one of the key factors affecting the cultivation of the uncultured microbes. Our study brings a new perspective to the role of dissolved organic sulfur in hadal ecosystems and also provides valuable information for optimizing the conditions of isolating related microbial taxa from the hadal environment.

Methamphetamine (METH) is a highly abused substance on a global scale and has the capacity to elicit toxicity within the central nervous system. The neurotoxicity induced by METH encompasses neuronal degeneration and cellular demise within the substantia nigra-striatum and hippocampus. Caffeic acid phenethyl ester (CAPE), a constituent of propolis, is a diminutive compound that demonstrates antioxidative and anti-inflammatory characteristics. Numerous investigations have demonstrated the safeguarding effects of CAPE in various neurodegenerative ailments. Our hypothesis posits that CAPE may exert a neuroprotective influence on METH-induced neurotoxicity via specific mechanisms. In order to validate the hypothesis, a series of experimental techniques including behavioral tests, immunofluorescence labeling, RNA sequencing, and western blotting were employed to investigate the neurotoxic effects of METH and the potential protective effects of CAPE. The results of our study demonstrate that CAPE effectively ameliorates cognitive memory deficits and anxiety symptoms induced by METH in mice. Furthermore, CAPE has been observed to attenuate the upregulation of neurotoxicity-associated proteins that are induced by METH exposure and also reduced the loss of hippocampal neurons in mice. Moreover, transcriptomics analysis was conducted to determine alterations in gene expression within the hippocampus of mice. Subsequently, bioinformatics analysis was employed to investigate the divergent outcomes and identify potential key genes. Interferon-stimulated gene 15 (ISG15) was successfully identified and confirmed through RT-qPCR, western blotting, and immunofluorescence techniques. Our research findings unequivocally demonstrated the neuroprotective effect of CAPE against METH-induced neurotoxicity, with ISG15 may have an important role in the underlying protective mechanism. These results offer novel perspectives on the treatment of METH-induced neurotoxicity.

Fungal keratitis is a severely vision-threatening corneal infection, where the prognosis depends on both fungal virulence and host immune defense. Inappropriate host responses can induce substantial inflammatory damage to the cornea. Therefore, in the treatment of fungal keratitis, it is important to concurrently regulate the immune response while efforts are made to eliminate the pathogen. Ebselen is a widely studied organo-selenium compound and has been demonstrated to have antifungal, antibacterial, anti-inflammatory, and oxidative stress-regulatory properties. The effectiveness of ebselen for the treatment of fungal keratitis remains unknown. In this study, ebselen was demonstrated to produce a marked inhibitory effect on Aspergillus fumigatus (A. fumigatus), including spore germination inhibition, mycelial growth reduction, and fungal biofilm disruption. The antifungal activity of ebselen was related to the cell membrane damage caused by thioredoxin (Trx) system inhibition-mediated oxidative stress. On the contrary, ebselen enhanced the antioxidation of Trx system in mammalian cells. Further, ebselen was proven to suppress the expressions of inflammatory mediators (IL-1β, IL-6, TNF-α, COX-2, iNOS, and CCL2) and reduce the production of oxidative stress-associated indicators (ROS, NO, and MDA) in fungi-stimulated RAW264.7 cells. In addition, ebselen regulated PI3K/Akt/Nrf2 and p38 MAPK signaling pathways, which contributed to the improvement of inflammation and oxidative stress. Finally, we verified the therapeutic effect of ebselen on mouse fungal keratitis. Ebselen improved the prognosis and reduced the fungal burden in mouse corneas. Expressions of inflammatory mediators, as well as the infiltration of macrophages and neutrophils in the cornea were also obviously decreased by ebselen. In summary, ebselen exerted therapeutic effects by reducing fungal load and protecting host tissues in fungal keratitis, making it a promising treatment for fungal infections.

Commented article: XU, Yushu; CHEN, Chao. Educational philosophy and educational practice in Confucianism. Trans/Form/Ação: Unesp journal of philosophy, Marília, v. 47, n. 5, “Eastern thought 2”, e02400189, 2024. Available at: https://revistas.marilia.unesp.br/index.php/transformacao/article/view/14955.

Seahorses are increasingly recognized for their nutritional potential, which underscores the necessity for comprehensive biochemical analyses. This study aims to investigate the fatty acid and amino acid compositions of eight seahorse species, including both genders of Hippocampus trimaculatus, Hippocampus kelloggi, Hippocampus abdominalis, and Hippocampus erectus, to evaluate their nutritional value. We employed Gas Chromatography-Mass Spectrometry (GC-MS) and High-Performance Liquid Chromatography (HPLC) to analyze the fatty acid and amino acid profiles of the seahorse species. GC-MS was used to detect 34 fatty acid methyl esters, while HPLC provided detailed amino acid profiles. GC-MS analysis demonstrated high precision with relative standard deviations (RSDs) generally below 2.53 %, satisfactory repeatability (RSDs from 6.55 % to 8.73 %), and stability (RSDs below 2.82 %). Recovery rates for major fatty acids ranged from 98.73 % to 109.12 %. HPLC analysis showed strong separation of amino acid profiles with theoretical plate numbers exceeding 5000. Precision tests yielded RSDs below 1.23 %, with reproducibility and stability tests showing RSDs below 2.73 % and 2.86 %, respectively. Amino acid recovery rates ranged from 97.58 % to 104.66 %. Nutritional analysis revealed significant variations in fatty acid content among the species. Female H. erectus showed higher levels of hexadecanoic acid and saturated fatty acids, while male H. abdominalis had lower concentrations of n-3 full cis 4,7,10,13,16,19-docosahexaenoic acid (DHA). Total lipid yields varied from 3.2491 % to 12.3175 %, with major fatty acids constituting 17.9717 %–74.6962 % of total lipids. In conclusion, this study provides essential insights into the fatty acid and amino acid composition of seahorses, supporting their potential as valuable dietary supplements. The differences between genders in specific fatty acids suggest a nuanced nutritional profile that could be exploited for targeted dietary applications. Further research is needed to explore the seasonal and environmental variations affecting seahorse biochemical composition.

This study investigated the effects of incorporating carbon nanotubes (CNTs) into rice husk ash (RHA) sustainable concrete on its mechanical properties, permeability and microstructure characterisation. Mechanical test results suggested that the addition of 0.10 % multiwalled CNTs (MWCNTs) yielded optimal results, with increases in the compressive strength, splitting tensile strength, flexural strength, and elastic modulus of the RHA concrete at 28 days of 7 %, 23.81 %, 17.5 %, and 1.0 %, respectively. However, with further addition of MWCNTs, the mechanical properties ultimately deteriorated. Further, the incorporation of CNTs enhanced the long-term performance of RHA sustainable concrete. The addition of 0.1 % MWCNTs and 15 % RHA yielded a 20 %, 14 %, and 66 % decrease in water absorption, porosity, and chloride diffusion coefficient compared to the mixture solely containing 15 % RHA. Scanning electron microscopy of this mixture revealed the filling and bridging effects of MWCNTs between the hydration products have enhanced the performance of RHA sustainable concrete.

ABSTRACT Ascospores, forcibly released into the air from perithecia, are the primary inoculum for Fusarium head blight. In Fusarium graminearum, the biological functions of four RNA-dependent RNA polymerases (RdRPs) (Fgrdrp1–4) have been reported, but their regulatory mechanisms are poorly understood and the function of Fgrdrp5 is still unknown. In this study, we found that in addition to Fgrdrp1 and Fgrdrp2, Fgrdrp5 also plays an important role in ascospore discharge, and they all participate in the generation of turgor pressure in a polyol-dependent manner. Moreover, these three genes all affect the maturation of ascospores. Deep sequencing and co-analysis of small RNA and mRNA certified that Fgrdrp1, Fgrdrp2, and Fgrdrp5 partly share their functions in the biogenesis and accumulation of exonic small interference RNA (ex-siRNA), and these three RdRPs negatively regulate the expression levels of ex-siRNA corresponding genes, including certain genes associated with ascospore development or discharge. Furthermore, the differentially expressed genes of deletion mutants, those involved in lipid and sugar metabolism or transport as well as sexual development-related transcription factors, may also contribute to the defects in ascospore maturation or ascospore discharge. In conclusion, our study suggested that the components of the dicer-dependent ex-siRNA-mediated RNA interference pathway include at least Fgrdrp1, Fgrdrp2, and Fgrdrp5.IMPORTANCEWe found that in addition to Fgrdrp1 and Fgrdrp2, Fgrdrp5 also plays important roles in ascospore maturation and ascospore discharge of Fusarium graminearum. These three RNA-dependent RNA polymerases participate in the biogenesis and accumulation of exonic small interference RNA and then regulate ascospore discharge.

Abstract Since ancient times, humans have learned to use fire and other heating methods to fight against dangerous pathogens, like cooking raw food, sterilizing surgical tools, and disinfecting other pathogen transmission media. However, it remains difficult for current heating methods to achieve extremely fast and highly efficient sterilization simultaneously. Herein, an ultrafast and uniform heating‐based strategy with outstanding bactericidal performance is proposed. Ultra‐precise laser manufacturing is used to fabricate the Joule heater which can be rapidly heated to 90 °C in 5 s with less than 1 °C fluctuation in a large area by real‐time temperature feedback control. An over 98% bactericidal efficiency on S. aureus for 30 s and on E. coli for merely 5 s is shown. The heating strategy shows a 360 times faster acceleration compared to the commonly used steam sterilization from the suggested guidelines by the Centers for Disease Control and Prevention (CDC), indicating that high temperatures with short duration can effectively disinfect microorganisms. As a proof of concept, this heating strategy can be widely applied to sterilizing cash and various objects to help protect the public from bacteria in daily life.

BackgroundUsing a pig model of cardiopulmonary bypass, we compared outcomes after cardioplegia either with our in-house “Huaxi-1” solution containing natural blood and crystalloid or with the entirely crystalloid, commercially available “histidine-tryptophan-ketoglutarate” solution.MethodsCardiopulmonary bypass was established in 13 healthy male pigs. Twelve of those animals were randomized to receive a single dose of either Huaxi-1 or entirely crystalloid cardioplegia, while the remaining animal was assigned to receive Huaxi-1 without randomization. All animals were then subjected to whole-heart ischemia for 90 min, followed by 2 h of reperfusion, after which myocardial injury was assessed in terms of cardiac function, myocardial pathology and levels of biomarkers in plasma, while levels of high-energy phosphate in myocardium were assayed using liquid chromatography.ResultsAnimals given Huaxi-1 cardioplegia required significantly less time to be weaned off bypass, they received significantly lower doses of norepinephrine, and they showed significantly higher levels (mean ± SD) of adenosine triphosphate (14 ± 4 vs. 8 ± 2 µg/mg, P = 0.005), adenosine diphosphate (16 ± 2 vs. 13 ± 2 µg/mg, P = 0.046), and total adenine nucleotide (37 ± 4 vs. 30 ± 3 µg/mg, P = 0.006) in myocardium after 2 h of reperfusion. They also showed less severe bleeding, edema and injury to mitochondria and myofibers in myocardium. The two groups did not differ significantly in doses of inotropic drugs received, cardiac output or levels of biomarkers in plasma.ConclusionsIn this animal model of healthy hearts subjected to 90 min of ischemia, Huaxi-1 cardioplegia may be superior to entirely crystalloid cardioplegia for promoting energy generation and attenuating ischemia/reperfusion injury in myocardium.

Highlights In this article, we contend that the bedrock of an equitable world lies in the profound recognition of love as the fundamental force permeating the cosmos. We believe that love is built into the essence of who we are. We posit that genuine progress toward an equitable world is elusive unless we place love, both for one another and for the natural world, at the core of our educational endeavors.

Abstract Background Carbapenem-resistant Pseudomonas aeruginosa (CRPA) infection has become a major public health concern. The recommendations for monotherapy and combination therapy in the current guidelines lack sufficient evidence to support them. The primary objective of this study is to determine the effectiveness of anti-Infective combination therapy compared to monotherapy in achieving clinical success in patients with CRPA infection and risk factors of clinical failure of monotherapy. Methods A retrospective study from Medical Information Mart for Intensive Care IV (MIMIC-IV) was conducted. We included adults with infections caused by CRPA. The outcomes of this study were clinical success, complete clinical success, and 28-day all-cause mortality. Results A total of 279 subjects were finally enrolled. The rate of clinical success for combination therapy was higher than that for monotherapy (73.1% versus 60.4%, p=0.028). Compared to clinical failure patients, patients in the clinical success group were more likely to die within 28 days after CRPA was found (48.3% versus 3.6%, p

Abstract Background The present study aimed to explore the maternal and perinatal risks in cases of monozygotic twins (MZT) following frozen-thawed embryo transfer (FET). Methods All twin births that were conceived following FET from 2007 to 2021 at Shanghai Ninth People’s Hospital in Shanghai, China were retrospectively reviewed. The exposure variable was twin type (monozygotic and dizygotic). The primary outcome was the incidence of neonatal death while secondary outcomes included hypertensive disorders of pregnancy, gestational diabetes, intrahepatic cholestasis of pregnancy, placenta previa, placental abruption, preterm premature rupture of the membranes, Cesarean delivery, gestational age, birth weight, weight discordance, stillbirth, birth defects, pneumonia, respiratory distress syndrome, necrotizing enterocolitis, and neonatal jaundice. Analysis of the outcomes was performed using logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs). The causal mediation analysis was conducted. A doubly robust estimation model was used to validate the results. Kaplan-Meier method was used to calculate survival probability. The sensitivity analysis was performed with a propensity score-based patient-matching model. Results Of 6101 dizygotic twin (DZT) and 164 MZT births conceived by FET, MZT showed an increased risk of neonatal death based on the multivariate logistic regression models (partially adjusted OR: 4.19; 95% CI, 1.23–10.8; fully adjusted OR: 4.95; 95% CI, 1.41–13.2). Similar results were obtained with the doubly robust estimation. Comparing MZT with DZT, the neonatal survival probability was lower for MZT (P

Abstract Background Rectus sheath block (RSB) and transversus abdominis plane block (TAPB) have been shown to reduce opioid consumption and decrease postoperative pain scores in abdominal surgeries. However, there are no reports about the one-puncture technique of RSB combined with TAPB for perioperative pain management during laparoscopic upper abdominal surgery. Methods A total of 58 patients were randomly assigned to the control group (C), the TAP group (T), and the one-puncture technique of RSB combined with TAPB group (RT). The patients in group C did not receive any regional block. The patients in group T received ultrasound-guided subcostal TAPB with 30 mL of 0.33% ropivacaine on each side. The patients in the RT group received a combination of RSB and TAPB with 15 mL of 0.33% ropivacaine in each plane by one puncture technique. All patients received postoperative patient-controlled intravenous analgesia (PCIA) after surgeries. The range of blocks was recorded 20 min after the completion of the regional block. The postoperative opioid consumption, pain scores, and recovery data were recorded, including the incidence of emergence agitation (EA), the times of first exhaust and off-bed activity, the incidence of postoperative nausea and vomiting, dizziness. Results The range of the one-puncture technique in group RT covered all areas of surgical incisions. The visual analogue scale (VAS) score of the RT group is significantly lower at rest and during coughing compared to groups T and C at 4, 8, 12, and 24 h after surgery, respectively (P

Traditional reliability evaluation of lighting sources often assesses only 50% of a lamp’s volume, which can lead to performance disparities and misapplications due to their limited reflection of real-world scenarios. To address the limitations, it is essential to adopt advanced asset management approaches that enhance awareness and provide a more comprehensive evaluation framework. This paper delves into the nuances of human-centric and integrative lighting asset management in Swedish public libraries, employing a qualitative field study to ascertain the alignment of current practices with these advanced lighting principles. Expanding library services to 20 high-latitude locations (>55° N) in Sweden, our research employed field observations, stakeholder interviews, and questionnaires, coupled with a thorough gap analysis, to understand the current landscape and stakeholder perceptions. Our findings reveal a dichotomy between the existing conditions of library lighting and the stakeholders’ experiences and expectations. Despite the intention to create conducive environments, there is a clear disconnect, with overt problems and covert challenges affecting user satisfaction and efficacy of lighting management. Managers, staff, and users reported varied concerns, including eye strain and discomfort, indicative of substantial room for improvement. The study advocates for a paradigm shift in not only lighting asset management but also reliability evaluation of lighting sources, moving toward continuous improvement, and enhanced awareness and training on human-centric and integrative lighting principles.