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AIM: To investigate the role of connective tissue growth factor (CTGF) and vascular endothelial growth factor (VEGF) in the protein profile of the aqueous humor in patients with proliferative diabetic retinopathy (PDR) following intravitreal injection of conbercept. METHODS: This study included 72 PDR patients and 8 cataract patients as controls. PDR patients were divided into 3 groups according to the intervals of 3, 5, and 7d between intravitreal conbercept (IVC, 0.5 mg/0.05 mL) injection and pars plana vitrectomy (PPV) performed. Aqueous humor samples were collected before and after IVC and PPV for VEGF and CTGF levels detected with enzyme-linked immunosorbent assay (ELISA). The differential proteomics of 10 patients who underwent PPV surgery 5d after IVC and 8 normal controls was studied, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed on the data, and the protein interaction network of 23 differential proteins was studied. RESULTS: Post-IVC, VEGF levels decreased and CTGF levels increased significantly in aqueous humor, with the CTGF/VEGF ratio rising significantly at all intervals. Liquid chromatography tandem mass spectrometry (LC-MS/MS) identified differentially expressed proteins between pre- and post-IVC samples. GO and KEGG analyses revealed involvement in immune response, stress response, complement and coagulation cascades, ferroptosis, and PPAR signaling pathways. PPI analysis highlighted key proteins like APOA1, C3, and transferrin (TF). ELISA assay confirmed the differential expression of proteins such as HBA1, SERPINA1, COL1A1, and ACTB, with significant changes in the IVC groups. CONCLUSION: The study demonstrates that IVC effectively reduces VEGF levels while increasing CTGF levels, thereby modifying the CTGF/VEGF ratio, and IVC significantly alters the protein profile in the aqueous humor of patients with PDR. Proteomic analysis reveals that these changes are associated with critical biological pathways and protein interactions involved in immune response, stress response, and cellular metabolism.

AIM: To investigate the involvement of pericyte-Müller glia interaction in retinal damage repair and assess the influence of suppressing the platelet-derived growth factor receptor β (PDGFRβ) signaling pathway in retinal pericytes on photoreceptor loss and Müller glial response. METHODS: Sprague-Dawley rats were exposed to intense light to induce retinal injury. Neutralizing antibody against PDGFRβ were deployed to block the signaling pathway in retinal pericytes through intravitreal injection. Retinal histology and Müller glial reaction were assessed following light injury. In vitro, normal and PDGFRβ-blocked retinal pericytes were cocultured with Müller cell line (rMC-1) to examine morphological and protein expression changes upon supplementation with light-injured supernatants of homogenized retinas (SHRs). RESULTS: PDGFRβ blockage 24h prior to intense light exposure resulted in a significant exacerbation of photoreceptor loss. The upregulation of GFAP and p-STAT3, observed after intense light exposure, was significantly inhibited in the PDGFRβ blockage group. Further upregulation of cytokines monocyte chemoattractant protein 1 (MCP-1) and interleukin-1β (IL-1β) was also observed following PDGFRβ inhibition. In the in vitro coculture system, the addition of light-injured SHRs induced pericyte deformation and upregulation of proliferating cell nuclear antigen (PCNA) expression, while Müller cells exhibited neuron-like morphology and expressed Nestin. However, PDGFRβ blockage in retinal pericytes abolished these cellular responses to light-induced damage, consistent with the in vivo PDGFRβ blockage findings. CONCLUSION: Pericyte-Müller glia interaction plays a potential role in the endogenous repair process of retinal injury. Impairment of this interaction exacerbates photoreceptor degeneration in light-induced retinal injury.

Abstract Background Chimeric antigen receptor (CAR)-T therapy has emerged as a promising treatment for hematologic malignancies. However, cytopenia remains one of the most frequent and challenging adverse effects of this therapy. Methods We conducted a retrospective analysis of 26 patients with relapsed/refractory aggressive B-cell lymphoma who received CAR-T therapy at our center. Subsequently, to investigate measures to address cytopenias following CAR-T therapy, we isolated and generated murine CAR-T cells and bone marrow-derived mesenchymal stem cells (MSCs), establishing a murine syngeneic CAR-T therapy model. We assessed the impact of MSC infusion on hematopoietic recovery post-CAR-T therapy by evaluating complete blood count, bone marrow hematopoietic stem cells and their subpopulations, bone marrow histomorphology, and hematopoiesis-related genes. Results All patients experienced cytopenias to varying degrees, with complete lineage involvement in half of the patients. Grade ≥ 3 cytopenias were observed in 88.46% of the patients. CAR-T therapy was associated with a higher incidence of biphasic, late-onset, or prolonged cytopenias. Survival analysis indicated that neutropenia and lymphopenia tended to be associated with better prognosis, whereas thrombocytopenia tended to be related to poorer outcomes. Through animal experiments, we discovered that MSCs infusion boosted HSCs and their long-term subpopulations, enhancing hematopoietic recovery, particularly in the megakaryocyte lineage, and mitigating bone marrow damage. Importantly, both in vitro and in vivo experiments demonstrated that MSCs did not compromise the activity or antitumor efficacy of CAR-T cells. Conclusions Our findings propose MSCs infusion as a promising strategy to address cytopenias, particularly thrombocytopenia, after CAR-T therapy. This approach could help overcome certain limitations of cellular immunotherapy by enhancing hematopoietic recovery without compromising the efficacy of CAR-T cells. Highlights 1 Cytopenia is a frequently observed adverse effect following CAR-T therapy, and it is often characterized by biphasic and prolonged patterns. 2 MSCs play a critical role in promoting hematopoietic recovery and mitigating bone marrow damage in a murine model of CAR-T therapy 3 The activity and antitumor efficacy of CAR-T cells were not impaired by MSCs. Graphical Abstract

Different initial microstructures significantly influence the final microstructures and mechanical properties of the intercritically annealed quenching and partitioning steels. Previous studies have primarily focused on the mechanism for the inheritance of different initial microstructures into the final microstructures, which affects the phase fraction and mechanical properties. However, these studies have overlooked the existence of an inheritance window in the intercritical annealing process. In this study, we investigated the inheritance window and explored the impact of varying initial microstructures on the reverse transformation of austenite, final phase fraction, and mechanical properties. Our findings reveal that the varying initial microstructure exhibits minimal influence on the final microstructure and mechanical properties for short or long annealing times. However, for the intercritical annealing treatment for 60 s, the initial microstructure of martensite with more nucleation sites accelerated the austenite reverse transformation fraction, enhanced the reverse-transformed austenite content, increased the primary martensite content, and improved the yield strength. Conversely, the coil-cooled sample, with initial microstructures consisting of ferrite and pearlite without dissoluble Mn-rich cementites, reduced the austenite reverse transformation rate, decreased the reverse-transformed austenite content, enhanced the ferrite and RA content, and improved ductility.

In this paper, for a bounded linear operator defined on a complex Banach space of infinite dimension, we consider the set of isolated points in its approximate point spectrum, which are eigenvalues of finite multiplicity; this set can be equal to the spectrum of the operator but without its upper semi-Fredholm spectrum, and this relation or equality defines in the literature a new spectral property called the property $ (\omega{ \pi }) $ and is a generalization of the classical a-Weyl theorem. We establish some characterizations and consequences about the property $ (\omega{ \pi }) $, some with topological aspects. Furthermore, we study this property through the Riesz functional calculus. Part of the spectral structure of a linear operator verifying property $ (\omega{ \pi }) $ is described, obtaining some associated properties.

Abstract Background Atmospheric particulate matter (PM) exposure-induced neuroinflammation is critical in mediating nervous system impairment. However, effective intervention is yet to be developed. Results In this study, we examine the effect of β-nicotinamide mononucleotide (NMN) supplementation on nervous system damage upon PM exposure and the mechanism of spatial regulation of lipid metabolism. 120 C57BL/6 male mice were exposed to real ambient PM for 11 days (subacute) or 16 weeks (sub-chronic). NMN supplementation boosted the level of nicotinamide adenine dinucleotide (NAD+) in the mouse brain by 2.04 times. This augmentation effectively reduced neuroinflammation, as evidenced by a marked decrease in activated microglia levels across various brain regions, ranging from 29.29 to 85.96%. Whole brain lipidomics analysis revealed that NMN intervention resulted in an less increased levels of ceramide (Cer) and lysophospholipid in the brain following subacute PM exposure, and reversed triglyceride (TG) and glycerophospholipids (GP) following sub-chronic PM exposure, which conferred mice with anti-neuroinflammation response, improved immune function, and enhanced membrane stability. In addition, we demonstrated that the hippocampus and hypothalamus might be the most sensitive brain regions in response to PM exposure and NMN supplementation. Particularly, the alteration of TG (60:10, 56:2, 60:7), diacylglycerol (DG, 42:6), and lysophosphatidylcholine (LPC, 18:3) are the most profound, which correlated with the changes in functional annotation and perturbation of pathways including oxidative stress, inflammation, and membrane instability unveiled by spatial transcriptomic analysis. Conclusions This study demonstrates that NMN intervention effectively reduces neuroinflammation in the hippocampus and hypothalamus after PM exposure by modulating spatial lipid metabolism. Strategies targeting the improvement of lipid homeostasis may provide significant protection against brain injury associated with air pollutant exposure.

Abstract Thermoelectrics converting heat and electricity directly attract broad attentions. To enhance the thermoelectric figure of merit, zT, one of the key points is to decouple the carrier-phonon transport. Here, we propose an entropy engineering strategy to realize the carrier-phonon decoupling in the typical SrTiO3-based perovskite thermoelectrics. By high-entropy design, the lattice thermal conductivity could be reduced nearly to the amorphous limit, 1.25 W m−1 K−1. Simultaneously, entropy engineering can tune the Ti displacement, improving the weighted mobility to 65 cm2 V−1 s−1. Such carrier-phonon decoupling behaviors enable the greatly enhanced μ W/κ L of ~5.2 × 103 cm3 K J−1 V−1. The measured maximum zT of 0.24 at 488 K and the estimated zT of ~0.8 at 1173 K in (Sr0.2Ba0.2Ca0.2Pb0.2La0.2)TiO3 film are among the best of n-type thermoelectric oxides. These results reveal that the entropy engineering may be a promising strategy to decouple the carrier-phonon transport and achieve higher zT in thermoelectrics.

Abstract HPV-positive and HPV-negative head and neck squamous cell carcinoma (HNSCC) are recognized as distinct entities. There remains uncertainty surrounding the causal effects of smoking and alcohol on the development of these two cancer types. Here we perform multivariable Mendelian randomization (MR) to evaluate the causal effects of smoking and alcohol on the risk of HPV-positive and HPV-negative HNSCC in 3431 cases and 3469 controls. Lifetime smoking exposure, as measured by the Comprehensive Smoking Index (CSI), is associated with increased risk of both HPV-negative HNSCC (OR = 3.03, 95%CI:1.75-5.24, P = 7.00E-05) and HPV-positive HNSCC (OR = 2.73, 95%CI:1.39-5.36, P = 0.003). Drinks Per Week is also linked with increased risk of both HPV-negative HNSCC (OR = 7.72, 95%CI:3.63-16.4, P = 1.00E-07) and HPV-positive HNSCC (OR = 2.66, 95%CI:1.06-6.68, P = 0.038). Smoking and alcohol independently increase the risk of both HPV-positive and HPV-negative HNSCC. These findings have important implications for understanding the modifying risk factors between HNSCC subtypes.

Abstract Cyclo[n]carbons have recently attracted significant attention owing to their geometric and electronic structures remaining largely unexplored in the condensed phase. In this work, we focus on two anti-aromatic cyclocarbons, namely C12 and C20. By designing two fully halogenated molecular precursors both including 4-numbered rings, we further extend the on-surface retro-Bergman ring-opening reaction, and successfully produce C12 and C20. The polyynic structures of C12 and C20 are unambiguously revealed by bond-resolved atomic force microscopy. More importantly, subtly positioning the C20 molecule into an atomic fence formed by Cl clusters allows us to experimentally probe its frontier molecular orbitals, yielding a transport gap of 3.8 eV measured from scanning tunneling spectroscopy. Our work may advance the field by easier synthesis of a series of cyclocarbons via on-surface retro-Bergman ring-opening strategy.

Abstract Near-infrared (NIR) phosphors based on Cr3+ doped garnets present great potential in the next generation of NIR light sources. Nevertheless, the huge searching space for the garnet composition makes the rapid discovery of NIR phosphors with high performance remain a great challenge for the scientific community. Herein, a generalizable machine learning (ML) strategy is designed to accelerate the exploration of innovative NIR phosphors via establishing the relationship between key parameters and emission peak wavelength (EPW). We propose a semi-supervised co-training model based on kernel ridge regression (KRR) and support vector regression (SVR), which successfully establishes an expanded dataset with unlabeled dataset (previously unidentified garnets), addressing the overfitting issue resulted from a small dataset and greatly improving the model generalization capability. The model is then interpreted to extract valuable insights into the contribution originated from different features. And a new type NIR luminescent material of Lu3Y2Ga3O12: Cr3+ (EPW~750 nm) is efficiently screened, which demonstrates a high internal (external) quantum efficiency of 97.1% (38.8%) and good thermal stability, particularly exhibiting promising application in the NIR phosphor-converted LEDs (pc-LED). These results suggest the strategy proposed in this work could provide new viewpoint and direction for developing NIR luminescence materials.

Abstract. Background:. The association and its population heterogeneities between low-density lipoprotein cholesterol (LDL-C) and all-cause and cardiovascular mortality remain unknown. We aimed to examine the dose-dependent associations of LDL-C levels with specific types of cardiovascular disease (CVD) mortality and heterogeneities in the associations among different population subgroups. Methods:. A total of 2,968,462 participants aged 35–75 years from China Health Evaluation And risk Reduction through nationwide Teamwork (ChinaHEART) (2014–2019) were included. Cox proportional hazard models and Fine–Gray subdistribution hazard models were used to estimate associations between LDL-C categories (

Radioisotopes tend to play important roles in many fields, such as industry, healthcare, agriculture, aerospace, etc. Radioisotope production is mainly through accelerators or research reactors, and high flux research reactor is one of the most effective approaches for radioisotope production. The physical basis of preparing radioisotope relies on nuclear reactions occurring in the reactor core, which includes fission, (n,γ), (n,α), and (n,p) reaction, etc. Among them, fission and (n,γ) reaction are most important in the nuclear reactor. For example, the 99Mo could be generated by uranium fission and extracting from the fission products, or through the radiative capture reaction from enriched 98Mo. As for the fission method, the irradiation target is gradually transitioning from high enriched uranium (HEU) target to low enriched uranium (LEU) target due to the requirement of non-proliferation. In this paper, studies on the impacts of different fission targets on radioisotope productions are conducted. Moreover, an optimized study on the radiative capture method is performed to improve the production efficiency. It is concluded that it is advantageous to use radiative capture method to generate radioisotopes in high flux reactor, which helps to improve the specific activity with environmental friendliness.

It is of great interest to overcome the problem of high-temperature oxidation of press-hardened steels (PHS) in press hardening with a cost-effective Cr alloying strategy. Therefore, since Cr is one of the expensive metals, the effect of Cr (Cr ≤ 3 wt%) content on the oxidation resistance of Cr–Si–Mn alloyed steels was investigated. It was found that Cr–Si–Mn alloyed PHS with a Cr content of about 1.5 wt% or less cannot form a continuous Cr2O3 layer during press hardening. However, when the Cr content reaches around 2.5 wt%, the PHS shows excellent oxidation resistance due to the formation of continuous Cr2O3 and amorphous SiO2 layers, as well as an Mn-rich oxide layer. However, further addition of 0.5 wt% could not significantly improve the oxidation resistance of this PHS. Moreover, the increase in Cr content simultaneously enhances the positive role of Si and Mn in high-temperature oxidation resistance. This work provides new insights into the design of the next generation of PHSs with economical and superior performance.

Inflammation can initiate osteolysis, which is the breakdown of bone by fully developed osteoclasts. The compound Oleandrin is recognized for its effects against inflammation and tumors. Our objective was to examine the effects of Oleandrin on osteoclastogenesis and osteolysis, both in vitro and in vivo. In vitro, the impact of Oleandrin on osteoclastogenesis was assessed using CCK-8 assays, TRAP staining, and bone resorption assays. Additionally, a mouse model of osteolysis caused by LPS injection into the calvaria was used to conduct an in vivo investigation, examining bone histomorphology, histology, and immunohistochemistry. In vitro, concentrations of 5 nM and 10 nM of Oleandrin were found to be non-cytotoxic based on the results obtained. In vitro, Oleandrin hindered the osteoclastogenesis and bone resorption induced by RANKL. Oleandrin successfully inhibited the phosphorylation of NF-κB p65 and PI3K p85 in osteolytic tissue, thereby suppressing LPS-induced inflammatory osteolysis in mice calvaria during the in vivo study. Furthermore, the Oleandrin-treated group exhibited a noteworthy decrease in the expression level of NFATc1, which is a crucial controller of osteoclastogenesis. To sum up, our discoveries indicate that Oleandrin could hinder osteoclastogenesis and bone resorption, thereby having the ability to suppress inflammation-induced osteolysis. The underlying mechanism involves the NF-κB/PI3K pathway and inhibition of NFATc1 activation. Therefore, the findings suggest that Oleandrin holds potential as a therapeutic remedy for osteolytic ailments.

Lumbar spinal stenosis is one of the most common causes of low back and leg pain. However, there is a lack of evidence-based guidelines for the treatment of lumbar spinal stenosis with integrated traditional Chinese medicine and western medicine. To standardize the diagnosis and treatment of lumbar spinal stenosis with a combination of traditional Chinese medicine and western medicine, this guideline strictly followed the relevant guiding principles for the development of guidelines both domestically and internationally. A multidisciplinary working group was established. We adopted the GRADE approach to grade the quality of evidence and the strength of recommendation. Finally recommendations on the treatment of lumbar spinal stenosis with integrated traditional Chinese medicine and western medicine were formed, aiming to standardize clinical practice. This guideline is for patients with all degrees of lumbar spinal stenosis.

Due to their high reactivity, volatile organic compounds (VOCs) can engage in physical and chemical reactions with particulate matter in the atmosphere, leading to air pollution. Extended exposure to VOCs may result in various health concerns, including respiratory system problems, neurological effects, skin and eye irritation, and an increased risk of certain cancers. Traditional benchtop mass spectrometers possess the advantages of high sensitivity and rapid analysis capabilities, but the large size typically confines their applications to professional laboratories. To overcome this limitation, portable mass spectrometers are emerging as a new tool for in-situ analysis. In this study, a portable mass spectrometer based on discontinuous atmosphere pressure interface was developed, which combined with a sub-vacuum plasma ionization source. Ion trap, known for its small size and adequate performance, was adopted in this miniaturized mass spectrometer. This portable mass spectrometer features a total weight of about 4.6 kg, with the dimensions of 217 mm×162 mm×106 mm, and operates with a power consumption under 150 W. On this design, a fully metallic solenoid valve was selected as the core component to limit atmospheric pressure, eliminating the need for the rubber tubing used in traditional pinch valves. Compared to traditional pinch valves, this solenoid valve ensures a more stable airflow during experiments. As a result, the repeatability and environmental adaptability of the portable mass spectrometer were improved. A certain delay marked as radio freqency (RF) delay was introduced between the injection and cooling periods, and the RF-delay time was optimized. Frequency scanning mode and amplitude scanning mode were tested in parallel. Despite of a trade-off in size, amplitude scanning offered improved resolution, enabling the differentiation of ions with close mass to charge ratios. After systematic optimization, satisfactory performances in mass resolution and sensitivity were achieved. The mass resolution of the mass spectrometer for dimethyl carbonate was improved to 0.2 u (FWHM), and a sensitivity of 60 μg/m3 for naphthalene was achieved. The capability of mixed VOCs was also validated using dimethyl carbonate and trimethyl phosphate. This mass spectrometer developed in this study, characterized by its high portability and satisfactory performance, is expected to hold great potential for applications in VOCs analysis.

Abstract Background Warm compresses are the routine treatment for Meibomian gland dysfunction (MGD) in daily life, but in order to achieve satisfactory efficacy, the treatment needs to be sustained over a long time, which can have an impact on the patient compliance. A more convenient warm compresses will help improve the patient compliance. Therefore, the purpose of the study is to investigate the efficacy and safety of the disposable eyelid warming masks for treatment of dry eye disease (DED) due to MGD. Methods This was a randomized, controlled, non-masked, two-center clinical trial. One hundred and forty-four patients were treated by the masks or the hot towel twice daily for 12 weeks. Patients were evaluated at baseline, 4-week and 12-week visits for subjective symptoms, objective signs and safety assessments, including ocular symptom scores, ocular surface disease index (OSDI), tear break-up time (BUT), corneal fluorescein staining (CFS), Schirmer I test (SIT), meibum quality, meibum expressibility, and adverse events (AEs). Results A totle of 134 patients were followed in the study. The mean age of the masks group (14 males and 52 females) and the hot towel group (20 males and 48 females) was 43.7 ± 13.5 years and 39.5 ± 13.9 years, respectively. At 4-week visit, there were significant statistical differences in ocular symptom scores, OSDI and CFS between two groups (P

Abstract Background Due to China’s rapid urbanization, many farmers have relocated to urban resettlement regions. There is limited research on the glycemic control of Type 2 diabetes mellitus (T2DM) farmers in these areas. This study examined their blood glucose control and its determinants. Methods This study took place from March 2021 to January 2022 in a resettlement community in Yiwu, Zhejiang Province, China. In the first phase, a quantitative survey of 181 T2DM farmers was conducted using a questionnaire to gather demographic data, blood glucose control status, disease cognition levels, and treatment compliance. Inclusion criteria were migrant workers with ≥ 3 months of residence and local household registration and T2DM patients who met the diagnostic criteria of the Chinese guidelines. In the second phase, qualitative research involved face-to-face, semi-structured interviews with 15 patients with varying blood glucose control levels to analyze their experiences. Results The blood glucose control rate in this particular group was 27.62%, and the average disease cognition score was 2.5 ± 0.75. Many patients (67.96%) had inadequate treatment compliance, specifically in monitoring compliance (4.45 ± 1.92) and regular review compliance (3.58 ± 1.74). Conclusion There is a need for tailored programs to improve glycemic control among resettled farmers. Enhancing disease awareness and treatment compliance through targeted education and support is crucial. Further studies are needed to evaluate different treatment regimens’ impact on glycemic control. Clinical trial number Not applicable.

Abstract The diagnosis of neurodegenerative diseases (NDDs) remains challenging, and existing therapeutic approaches demonstrate little efficacy. NDD drug delivery can be achieved through the utilization of nanostructures, hence enabling multimodal NDD theranostics. Nevertheless, both biomembrane and non-biomembrane nanostructures possess intrinsic shortcomings that must be addressed by hybridization to create novel nanostructures with versatile applications in NDD theranostics. Hybrid nanostructures display improved biocompatibility, inherent targeting capabilities, intelligent responsiveness, and controlled drug release. This paper provides a concise overview of the latest developments in hybrid nanostructures for NDD theranostics and emphasizes various engineering methodologies for the integration of diverse nanostructures, including liposomes, exosomes, cell membranes, and non-biomembrane nanostructures such as polymers, metals, and hydrogels. The use of a combination technique can significantly augment the precision, intelligence, and efficacy of hybrid nanostructures, therefore functioning as a more robust theranostic approach for NDDs. This paper also addresses the issues that arise in the therapeutic translation of hybrid nanostructures and explores potential future prospects in this field.

Abstract There are several gaps in the field of digital inequity in education because it is still in its initial stage. To fill the research gaps, this study has revealed a complex landscape of problems and solutions. The analysis highlights the urgent need to address digital inequity that prevents equal access to educational resources and opportunities. While the challenges are numerous, the solutions are also diverse. Addressing cultural norms and stereotypes that perpetuate gender-based inequity is crucial, along with investing in gender-sensitive technology and infrastructure. Promoting digital literacy among all learners is also essential to empower them in the digital age. By taking a comprehensive approach that combines policy changes, technological advancements, and educational strategies, we can hope to bridge the digital inequity and create a more equitable and inclusive education system. Future research could highlight cross-cultural and cross-contextual studies, longitudinal studies, and integration of multiple methodologies.

Abstract In recent years, museums have become valuable venues for students to develop career awareness outside of school. However, optimizing the educational potential of museums and improving learners’ outcomes presents a significant challenge in museum learning design. This study integrates three main game elements—goals, stories, and role-playing—into museum visits to design a Gamified Learning Activity (GLA). To verify the effectiveness of the GLA, we conducted a quasi-experiment with 66 elementary school students at the Handicraft Museum. Using a mixed-methods approach with convergent parallel design, we collected quantitative data from knowledge tests and qualitative data from DAST (Draw-a-Scientist-Test) and interviews for a comprehensive analysis. The results showed that learners who participated in the GLA paid more attention to the details of the handicrafts, appreciated the craftsmen more, and eliminated stereotypes about the age of craftsmen. This indicates that the GLA not only enhances learners’ acquisition of museum knowledge but also has a profound impact on their non-cognitive aspects, such as career awareness.

Abstract Kitaev interactions, arising from the interplay of frustration and bond anisotropy, can lead to strong quantum fluctuations and, in an ideal case, to a quantum-spin-liquid state. However, in many nonideal materials, spurious non-Kitaev interactions typically promote a zigzag antiferromagnetic order in the d-orbital transition-metal compounds. Here, by combining neutron scattering with muon-spin rotation and relaxation techniques, we provide mechanism insights into the exotic properties of Na2Co2TeO6, a candidate material of the Kitaev model. Below T N, the zero-field muon-spin relaxation rate becomes almost constant (~0.45 μs−1). We attribute this temperature-independent relaxation rate to the strong quantum fluctuations, as well as to the frustrated Kitaev interactions. As the magnetic field increases, neutron scattering data indicate a broader spin-wave excitation at the K-point. Therefore, quantum fluctuations seem not only robust but are even enhanced by the applied magnetic field. Our findings provide valuable hints for understanding the onset of the quantum-spin-liquid state in Kitaev materials.

Abstract Background Fetal inflammatory response syndrome (FIRS) is a systemic inflammatory response caused by the activation of the fetal immune system. The serological diagnostic criterion for fetal inflammatory response syndrome is a cord blood interleukin-6 concentration that exceeds 11 pg/mL, while pathologic evidence indicates the presence of funisitis or chorionic vasculitis. It can affect all systems of the fetus. Alterations in patients’ hematopoietic system are primarily reflected by changes in peripheral blood leukocyte and neutrophil counts. Case presentation We performed placental pathology to identify FIRS and showed two cases of neonatal leukemoid reaction caused by FIRS. These two babies’ alterations in hematopoietic system resolves spontaneously with the inflammation relief, without specific interventions. During the 16‑month and14- month follow‑up period, their motor and intellectual development was normal. Conclusions . Neonatal leukemoid reaction is a reactive disease characterized by abnormal blood parameters similar to those of leukemia, but not leukemia. It is an aberrant hematopoietic response that typically resolves spontaneously with cause relief without requiring specific interventions.

Abstract TP53 mutation (TP53-mut) correlates with inferior survival in many cancers, whereas its prognostic role in diffuse large B-cell lymphoma (DLBCL) is still in controversy. Therefore, more precise risk stratification needs to be further explored for TP53-mut DLBCL patients. A set of 2637 DLBCL cases from multiple cohorts, was enrolled in our analysis. Among the 2637 DLBCL patients, 14.0% patients (370/2637) had TP53-mut. Since missense mutations account for the vast majority of TP53-mut DLBCL patients, and most non-missense mutations affect the function of the P53 protein, leading to worse survival rates, we distinguished patients with missense mutations. A TP53 missense mutation risk model was constructed based on a 150-combination machine learning computational framework, demonstrating excellent performance in predicting prognosis. Further analysis revealed that patients with high-risk missense mutations are significantly associated with early progression and exhibit dysregulation of multiple immune and metabolic pathways at the transcriptional level. Additionally, the high-risk group showed an absolutely suppressed immune microenvironment. To stratify the entire cohort of TP53-mut DLBCL, we combined clinical characteristics and ultimately constructed the TP53 Prognostic Index (TP53PI) model. In summary, we identified the truly high-risk TP53-mut DLBCL patients and explained this difference at the mutation and transcriptional levels.

Abstract Background We aimed to explore the impact of adherence to Life’s Simple 7 (LS7) metrics on risk of obstructive sleep apnea (OSA), and the impact of inflammation on the association, in adults in the United States. Methods Data from 13,825 community-dwelling adults aged ≥ 20 years recruited in the National Health and Nutrition Examination Surveys (NHANES) 2005–2008, 2015–2018 was analyzed. The LS7 score was calculated based on the AHA definition of LS7 metrics. The diagnosis of OSA was based on self-reported symptoms of sleep disturbance using a standard questionnaire. The Multivariable Apnea Prediction (MAP) Index score was also calculated to assess the risk of OSA. Log-binominal regression and negative binomial regression were performed to estimate the associations between LS7 and OSA and MAP index, with odds ratios (ORs) and prevalence ratios (PRs) and their 95% confidence intervals (CIs) calculated. Mediation analysis was performed to estimate the mediating effects of inflammatory indicators on the associations. Results A total of 4473 participants (32.4%) had OSA, and the mean MAP index was 0.39. In fully adjusted log-binominal regression models, with total score 8, respectively (P for trend 8, respectively (P for trend

Abstract Childhood overweight/obesity is a serious problem that has not been adequately addressed. As a key factor affecting weight gain, the association between dietary intake with childhood overweight and obesity is still unclear. The objective of this study was to analyze the association between sociodemographic, lifestyle factors and dietary intake with overweight or obesity. We used data from a large cross-sectional National Health and Nutrition Examination Survey (NHANES). The U.S. children aged 6–15 years with both weight data and dietary data were included. For univariate analysis of sociodemographic data, t tests was performed for continuous variables and chi-square tests was performed for discrete variables. Dietary intakes were described by median and quartile, and differences in dietary intake between children with normal weight and children with overweight or obesity were compared by rank sum tests. A modern statistical shrinkage technique, LASSO regression was used to examine the association between dietary intake and childhood obesity. Our study confirms that Hispanic ethnicity, increasing age, passive exposure to smoking, higher protein intake, and higher caffeine intake were positively associated with child overweight or obesity. Additionally, non-Hispanic White race, higher physical activity levels, higher household income, and higher vitamin A intake were negatively associated with child overweight or obesity.

Abstract Follicular lymphoma (FL) exhibits considerable variability in biological features and clinical trajectories across patients. To dissect the diversity of FL, we utilized a Bernoulli mixture model to identify genetic subtypes in 713 pre-treatment tumor tissue samples. Our analysis revealed the existence of five subtypes with unique genetic profiles that correlated with clinicopathological characteristics. The clusters were enriched in specific mutations as follows: CS (CREBBP and STAT6), TT (TNFAIP3 and TP53), GM (GNA13 and MEF2B), Q (quiescent, for low mutation burden), and AR (mutations of mTOR pathway-related genes). The subtype Q was enriched for patients with stage I disease and associated with a lower proliferative history than the other subtypes. The AR subtype was unique in its enrichment for IgM-expressing FL cases and was associated with advanced-stage and more than 4 nodal sites. The existence of subtypes was validated in an independent cohort of 418 samples from the GALLIUM trial. Notably, patients assigned to the TT subtype consistently experienced inferior progression-free survival when treated with immunochemotherapy. Our findings offer insight into core pathways distinctly linked with each FL cluster and are expected to be informative in the era of targeted therapies.

Abstract Sandification can degrade the strength and quality of dolomite, and to a certain extent, compromise the stability of a tunnel's surrounding rock as an unfavorable geological boundary. Sandification degree classification of sandy dolomite is one of the non-trivial challenges faced by geotechnical engineering projects such as tunneling in complex geographical environments. The traditional methods quantitatively measuring the physical parameters or analyzing some visual features are either time-consuming or inaccurate in practical use. To address these issues, we, for the first time, introduce the convolutional neural network (CNN)-based image classification methods into dolomite sandification degree classification task. In this study, we have made a significant contribution by establishing a large-scale dataset comprising 5729 images, classified into four distinct sandification degrees of sandy dolomite. These images were collected from the vicinity of a tunnel located in the Yuxi section of the CYWD Project in China. We conducted comprehensive classification experiments using this dataset. The results of these experiments demonstrate the groundbreaking achievement of CNN-based models, which achieved an impressive accuracy rate of up to 91.4%. This accomplishment underscores the pioneering role of our work in creating this dataset and its potential for applications in complex geographical analyses.

Abstract In this paper, we study the reentrant Hawking–Page transition in the grand canonical ensemble of Gauss–Bonnet AdS spacetime. We find that the four-dimensional Gauss–Bonnet hyperbolic AdS black hole always has a reentrant Hawking–Page transition in the range of electric potential $$0\Phi _{tr}$$ Φ > Φ tr , the Hawking–Page transition disappears. In the spacetime of five and higher dimensional Gauss–Bonnet hyperbolic AdS black hole, the reentrant Hawking–Page transition is solely observed to occur when the electric potential $$\Phi $$ Φ lies between two specific thresholds ( $$\Phi _{c}\Phi _{tr}$$ Φ > Φ tr ). We give the coexistence line, the triple point and critical point of the Hawking–Page transition in the phase diagram of the Gauss–Bonnet hyperbolic AdS black hole. The observed reentrant Hawking–Page transitions and triple points in the context of Gauss–Bonnet hyperbolic AdS black holes may correspond to the phase transitions and triple points in QCD phase diagrams, following the spirit of the AdS/CFT correspondence. To be a complete research, the Hawking–Page transition of d-dimensional charged spherical Gauss–Bonnet-AdS black hole in the grand canonical ensemble is also study in the Appendix, for which there exists a standard Hawking–Page transition with the transition temperature depending on the Gauss–Bonnet constant $$\alpha $$ α .

ABSTRACT Aims/Introduction Diabetes has been related to an increased risk of oral cancer. Nevertheless, the impact of diabetes on the outcome of individuals with oral and oropharyngeal cancer is not clear. In this study, a meta‐analysis was carried out to assess the link between diabetes and the survival of individuals with oral and oropharyngeal cancer. Materials and Methods Relevant cohort studies for the meta‐analysis objective were obtained through searching electronic databases, such as PubMed, Web of Science and Embase. The data were combined using a random effects model that accounted for differences between studies. Results A total of 10 cohorts involving 21,871 patients with oral and oropharyngeal cancer were included. Pooled results suggest that compared with those with normoglycemia, oral and oropharyngeal cancer patients with diabetes were associated with a poor overall survival (hazard ratio 1.69, 95% confidence interval 1.29–2.22, P 0.05). In addition, diabetes was also associated with a poor progression‐free survival of patients with oral and oropharyngeal cancer (hazard ratio 1.61, 95% confidence interval 1.30–1.99, P

Background: Bone marrow adipose tissue (BMAT) represents > 10% fat mass in healthy humans and can be measured by magnetic resonance imaging (MRI) as the bone marrow fat fraction (BMFF). Human MRI studies have identified several diseases associated with BMFF but have been relatively small scale. Population-scale studies therefore have huge potential to reveal BMAT’s true clinical relevance. The UK Biobank (UKBB) is undertaking MRI of 100,000 participants, providing the ideal opportunity for such advances. Objective: To establish deep learning for high-throughput multi-site BMFF analysis from UKBB MRI data. Materials and methods: We studied males and females aged 60–69. Bone marrow (BM) segmentation was automated using a new lightweight attention-based 3D U-Net convolutional neural network that improved segmentation of small structures from large volumetric data. Using manual segmentations from 61–64 subjects, the models were trained to segment four BM regions of interest: the spine (thoracic and lumbar vertebrae), femoral head, total hip and femoral diaphysis. Models were tested using a further 10–12 datasets per region and validated using datasets from 729 UKBB participants. BMFF was then quantified and pathophysiological characteristics assessed, including site- and sex-dependent differences and the relationships with age, BMI, bone mineral density, peripheral adiposity, and osteoporosis. Results: Model accuracy matched or exceeded that for conventional U-Nets, yielding Dice scores of 91.2% (spine), 94.5% (femoral head), 91.2% (total hip) and 86.6% (femoral diaphysis). One case of severe scoliosis prevented segmentation of the spine, while one case of Non-Hodgkin Lymphoma prevented segmentation of the spine, femoral head and total hip because of T2 signal depletion; however, successful segmentation was not disrupted by any other pathophysiological variables. The resulting BMFF measurements confirmed expected relationships between BMFF and age, sex and bone density, and identified new site- and sex-specific characteristics. Conclusions: We have established a new deep learning method for accurate segmentation of small structures from large volumetric data, allowing high-throughput multi-site BMFF measurement in the UKBB. Our findings reveal new pathophysiological insights, highlighting the potential of BMFF as a novel clinical biomarker. Applying our method across the full UKBB cohort will help to reveal the impact of BMAT on human health and disease.

The completely autotrophic nitrogen removal over nitrite (CANON) process is significantly hindered by prolonged start-up periods and unstable nitrogen removal efficiency. In this study, a novel umbrella basalt fiber (BF) carrier with good biological affinity and adsorption performance was used to initiate the CANON process. The CANON process was initiated on day 64 in a sequencing batch reactor equipped with umbrella BF carriers. During this period, the influent NH4+-N concentration gradually increased from 100 to 200 mg·L−1, and the dissolved oxygen was controlled below 0.8 mg L−1. Consequently, an average ammonia nitrogen removal efficiency (ARE) and total nitrogen removal efficiency (TNRE) of ∼90 and 80% were achieved, respectively. After 130 days, ARE and TNRE remained stable at 92 and 81.1%, respectively. This indicates a reliable method for achieving rapid start-up and stable operation of the CANON process. Moreover, Candidatus Kuenenia and Candidatus Brocadia were identified as dominant anammox genera on the carrier. Nitrosomonas was the predominant genus among ammonia-oxidizing bacteria. Spatial differences were observed in the microbial population of umbrella BF carriers. This arrangement facilitated autotrophic nitrogen removal in a single reactor. This study indicates that the novel umbrella BF carrier is a highly suitable biocarrier for the CANON process. HIGHLIGHTS The umbrella basalt fiber (BF) carrier CANON reactor achieved rapid start-up and stable operation.; There were spatial distribution differences between AOB and anammox bacteria in the umbrella BF carrier.; Umbrella BF carriers enhance the abundance and diversity of microbial communities.;

Abstract Background RNA sequencing (RNA-seq) is widely used for gene expression profiling and quantification. Quantitative RNA sequencing usually requires cell counting and spike-in, which is not always applicable to many samples. Here, we present a novel quantitative RNA sequencing method independent of spike-ins or cell counting, named siqRNA-seq, which can be used to quantitatively profile gene expression by utilizing gDNA as an internal control. Single-stranded library preparation used in siqRNA-seq profiles gDNA and cDNA with equal efficiency. Results To quantify mRNA expression levels, siqRNA-seq constructs libraries for total nucleic acid to establish a model for expression quantification. Compared to Relative Quantification RNA-seq, siqRNA-seq is technically reliable and reproducible for expression profiling but also can sequence reads from gDNA which can be used as an internal reference for accurate expression quantification. Applying siqRNA-seq to investigate the effects of actinomycin D on gene expression in HEK293T cells, we show the advantages of siqRNA-seq in accurately identifying differentially expressed genes between samples with distinct global mRNA levels. Furthermore, we analyzed factors influencing the downward trend of gene expression regulated by ActD using siqRNA-seq and found that mRNA with m6A modification exhibited a faster decay rate compared to mRNA without m6A modification. Additionally, applying this technique to the quantitative analysis of seven tumor cell lines revealed a high degree of diversity in total mRNA expression among tumor cell lines. Conclusions Collectively, siqRNA-seq is a spike-in independent quantitative RNA sequencing method, which creatively uses gDNA as an internal reference to absolutely quantify gene expression. We consider that siqRNA-seq provides a convenient and versatile method to quantitatively profile the mRNA landscape in various samples.

T-shaped mortise and tenon members are the main structure of traditional Chinese furniture. In this paper, the double-dovetail joint used for face-to-face joint of rubber wood (Hevea brasiliensis Muell. Arg) is transformed into a new type of double-dovetail joint and rounded double-dovetail joint for T-shaped members of point joint structure. The ultimate pull-out test and bending strength test were carried out on the two structures and three structures of oval mortise, round rod mortise and right angle mortise. The results show that the ultimate pull-out force of the round double-dovetail joint is 39% higher than that of the double-dovetail joint, and the bending resistance capacity is 8.9% higher, and the strength and stability are better than those of other split mortises and tenons, which proves that this structure can be used in actual production, and also proves that the mortise and tenon connected by the surface has the possibility of transforming into a point connection structure. The concave structure of the rounded double-dovetail joint makes the mortise and tenon fit well, the tenon squeezed tight, and a good bonding effect was achieved. This structure can also provide greater friction and resistance, delay rubber adhesive failure and improve the stability.

Abstract Background The limited regenerative capacity of damaged neurons in adult mammals severely restricts neural repair. Although stem cell transplantation is promising, its clinical application remains challenging. Direct reprogramming, which utilizes cell plasticity to regenerate neurons, is an emerging alternative approach. Methods We utilized primary postnatal cortical astrocytes for reprogramming induced neurons (iNs) through the viral-mediated overexpression of the transcription factors Ngn2 and Pax6 (NP). Fluorescence-activated cell sorting (FACS) was used to enrich successfully transfected cells, followed by single-cell RNA sequencing (scRNA-seq) using the 10 × Genomics platform for comprehensive transcriptomic analysis. Results The scRNA-seq revealed that NP overexpression led to the differentiation of astrocytes into iNs, with percentages of 36% and 39.3% on days 4 and 7 posttransduction, respectively. CytoTRACE predicted the developmental sequence, identifying astrocytes as the reprogramming starting point. Trajectory analysis depicted the dynamic changes in gene expression during the astrocyte-to-iN transition. Conclusions This study elucidates the molecular dynamics underlying astrocyte reprogramming into iNs, revealing key genes and pathways involved in this process. Our research contributes novel insights into the molecular mechanisms of NP-mediated reprogramming, suggesting avenues for optimizing the efficiency of the reprogramming process.

Abstract Methicillin-resistant Staphylococcus aureus (MRSA) is a serious threat to patients with nosocomial infections, and infection is strongly associated with biofilm formation. Gallic acid (GA) is a natural bioactive compound found in traditional Chinese medicines that exerts potent antimicrobial activity. However, the anti-MRSA biofilm efficacy of GA remained to be determined. This study investigated the antimicrobial activities of GA against MRSA and the mechanisms involved. The results revealed the significant antibacterial and antibiofilm activities of GA. The minimal inhibitory concentration of GA against MRSA was 32 μg/mL and a growth curve assay confirmed the significant inhibitory effect of GA on planktonic MRSA. Crystal violet and XTT assays showed that 8 µg/mL GA effectively inhibited the formation of new biofilms and disrupted existing biofilms by reducing both biofilm biomass and metabolic activities. Alkaline phosphatase and β-galactosidase leakage assays and live/dead staining provided evidence that GA disrupted the integrity of bacterial cell walls and membranes within the biofilm. Scanning electron microscopy observations showed that GA significantly inhibited bacterial adhesion and aggregation, affecting the overall structure of the biofilm. Bacterial adhesion, polysaccharide intercellular adhesion (PIA) production and real-time quantitative PCR assay confirmed that GA inhibited bacterial adhesion, PIA synthesis, and the expression of icaAD and sarA. These results suggested that GA inhibited biofilm formation by inhibiting the expression of sarA, then downregulating the expression of icaA and icaD, thereby reducing the synthesis of PIA to attenuate the adhesion capacity of MRSA. GA is therefore a promising candidate for development as a pharmaceutical agent for the prevention and treatment of bacterial infections caused by MRSA.

Abstract Background Infectious keratitis, a significant contributor to blindness, with fungal keratitis accounting for nearly half of cases, poses a formidable diagnostic and therapeutic challenge due to its delayed clinical presentation, prolonged culture times, and the limited availability of effective antifungal medications. Furthermore, infections caused by rare fungal strains warrant equal attention in the management of this condition. Case presentation A case of fungal keratitis was presented, where corneal scraping material culture yielded pink colonies. Lactophenol cotton blue staining revealed distinctive spore formation consistent with the Fusarium species. Further analysis using Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS) identified the causative agent as Fusarium proliferatum. However, definitive diagnosis of Pseudonectria foliicola infection was confirmed through ITS sequencing. The patient’s recovery was achieved with a combination therapy of voriconazole eye drops and itraconazole systemic treatment. Conclusion Pseudonectria foliicola is a plant pathogenic bacterium that has never been reported in human infections before. Therefore, ophthalmologists should consider Pseudonectria foliicola as a possible cause of fungal keratitis, as early identification and timely treatment can help improve vision in most eyes.

Abstract Objective To investigate any connections between urinary organophosphorus pesticide (OPP) metabolites and adiposity measures. Methods In this study, data from the National Health and Nutrition Examination Survey (NHANES) projects from 2003 to 2008, 2011 to 2012, and 2015 to 2018 were analysed. Obesity was defined as a body mass index (BMI) of 30 kg/m² or higher. Abdominal obesity was defined as a waist circumference (WC) over 102 cm for men and 88 cm for women. Four urinary OPP metabolites (dimethyl phosphate [DMP], diethyl phosphate [DEP], dimethyl phosphorothioate [DMTP], and diethyl phosphorothioate [DETP]) and adiposity measures were examined using multiple linear regression and logistic regression analyses. The correlations between a variety of urinary OPP metabolites and the prevalence of obesity were investigated using weighted quantile sum regression and quantile g-computation regression. Results In this analysis, a total of 9,505 adults were taken into account. There were 49.81% of male participants, and the average age was 46.00 years old. The median BMI and WC of the subjects were 27.70 kg/m2 and 97.10 cm, respectively. Moreover, 35.60% of the participants were obese, and 54.42% had abdominal obesity. DMP, DMTP, and DETP were discovered to have a negative correlation with WC and BMI in the adjusted models. DMP (OR = 0.93 [95% CI: 0.89–0.98]), DEP (OR = 0.94 [95% CI: 0.90–0.99]), DMTP (OR = 0.91 [95% CI: 0.86–0.95]), and DETP (OR = 0.85 [95% CI: 0.80–0.90]) exhibited negative associations with obesity prevalence. Similar correlations between the prevalence of abdominal obesity and the urine OPP metabolites were discovered. Moreover, the mixture of urinary OPP metabolites showed negative associations with adiposity measures, with DMTP and DETP showing the most significant effects. Conclusion Together, higher levels of urinary OPP metabolites in the urine were linked to a decline in the prevalence of obesity.

Abstract Background Generalized anxiety (GA) is showing a high prevalence among adolescents nowadays; investigations on influencing factors and potential mechanisms are important to inform intervention development. The present two-wave study investigated the ways in which family functioning predicted GA six months later among adolescents, by considering the mediating role of self-identity and cognitive flexibility. Methods Adolescents were recruited from 27 randomly selected classes in two secondary schools in Chongqing and Fujian Province, China. Survey questionnaires assessing family functioning, self-identity, cognitive flexibility and GA were obtained from 1223 adolescents (M age = 13.14, SD = 1.35) at two time points of the 6-month interval. Results The association between family functioning (T1) and GA (T2) was significant (r= -0.152, p

Abstract Background Alternaria alternata is the primary pathogen of potato leaf spot disease, resulting in significant potato yield losses globally. Endophytic microorganism-based biological control, especially using microorganisms from host plants, has emerged as a promising and eco-friendly approach for managing plant diseases. Therefore, this study aimed to isolate, identify and characterize the endophytic fungi from healthy potato leaves which had great antifungal activity to the potato leaf spot pathogen of A. alternata in vitro and in vivo. Results An endophytic fungal strain SD1-4 was isolated from healthy potato leaves and was identified as Talaromyces muroii through morphological and sequencing analysis. The strain SD1-4 exhibited potent antifungal activity against the potato leaf spot pathogen A. alternata Lill, with a hyphal inhibition rate of 69.19%. Microscopic and scanning electron microscope observations revealed that the strain SD1-4 grew parallel to, coiled around, shrunk and deformed the mycelia of A. alternata Lill. Additionally, the enzyme activities of chitinase and β-1, 3-glucanase significantly increased in the hyphae of A. alternata Lill when co-cultured with the strain SD1-4, indicating severe impairment of the cell wall function of A. alternata Lill. Furthermore, the mycelial growth and conidial germination of A. alternata Lill were significantly suppressed by the aseptic filtrate of the strain SD1-4, with inhibition rates of 79.00% and 80.67%, respectively. Decrease of leaf spot disease index from 78.36 to 37.03 was also observed in potato plants treated with the strain SD1-4, along with the significantly increased plant growth characters including plant height, root length, fresh weight, dry weight, chlorophyll content and photosynthetic rate of potato seedlings. Conclusion The endophyte fungus of T. muroii SD1-4 isolated from healthy potato leaves in the present study showed high biocontrol potential against potato leaf spot disease caused by A. alternata via direct parasitism or antifungal metabolites, and had positive roles in promoting potato plant growth.

Objetive: Culturing liquid hyphae with Hericium erinaceus pure strain. The medium was optimized to increase the content of Hericium erinaceus mycelium phenolic extracts. The composition of Hericium erinaceus mycelium phenolic extracts was analyzed, and the effects of phenolic extracts from Hericium erinaceus mycelium on lactic acid bacteria were also studied. Methods: Orthogonal design was used to study the effect on the total phenol content in liquid mycelium, and HPD-826 macroporous adsorption resin was used to purify it, and then HPLC-MS was used to determine its composition. Finally, adding the purified product to the lactic acid bacteria culture mediumm, and detected the effect on the number of viable lactic acid bacteria and its acid-production ability. Results: When the carbon source potato was 14%, nitrogen source peptone was 2% and inorganic salt MgSO4 was 0.3%, the total phenol content of Hericium erinaceus mycelium reached 0.783 mg/g. Sixteen monomeric phenols were identified from the phenolic extract of Hericium erinaceus mycelium, accounting for 88.27%. The main monomeric phenols were gallic acid-O-glucoside, p-coumaric acid-O-gallic acid glucoside, ferulic acid, catechin benzyl sulfide, gallic acid and caffeic acid. Adding phenol extraction solution from Hericium erinaceus mycelium to MRS medium of Lactobacilluscasei, Lactobacillus acidophilus and Streptococcus intestinalis could increase the number of viable bacteria of three kinds of lactic acid bacteria. Conclusion: Phenolic extract from Hericium erinaceus mycelium can promote the growth of lactic acid bacteria and provide new resource raw materials for functional food.

Abstract. Background:. Although the treatment of peripheral T-cell lymphoma (PTCL) has undergone advancements during the past several years, the response rate and long-term effects with respect to patients with PTCL remain unsatisfactory—particularly for relapsed or refractory (R/R) patients. This phase II trial was designed to explore the efficacy and safety of an all-oral regimen of chidamide plus prednisone, cyclophosphamide, and thalidomide (CPCT) for R/R PTCL patients who could not tolerate the standard chemotherapy for a variety of reasons. Methods:. We conducted a multicenter phase II clinical trial in which we combined chidamide (30 mg twice weekly) with prednisone (20 mg daily after breakfast), cyclophosphamide (50 mg daily after lunch), and thalidomide (100 mg daily at bedtime) (the CPCT regimen) for a total of fewer than 12 cycles as an induction-combined treatment period, and then applied chidamide as single-drug maintenance. Forty-five patients were ultimately enrolled from August 2016 to April 2021 with respect to Chinese patients at nine centers. Our primary objective was to assess the overall response rate (ORR) after the treatment with CPCT. Results:. Of the 45 enrolled patients, the optimal ORR and complete response (CR)/CR unconfirmed (CRu) were 71.1% (32/45) and 28.9% (13/45), respectively, and after a median follow-up period of 56 months, the median progression-free survival (PFS) and overall survival (OS) were 8.5 months and 17.2 months, respectively. The five-year PFS and OS rates were 21.2% (95% confidence interval [CI], 7.9–34.5%) and 43.8% (95% CI, 28.3–59.3%), respectively. The most common adverse event was neutropenia (20/45, 44.4%), but we observed no treatment-related death. Conclusion:. The all-oral CPCT regimen was an effective and safe regimen for R/R PTCL patients who could not tolerate standard chemotherapy for various reasons. Trial Registration:. ClinicalTrials.gov, NCT02879526.

Abstract Background Fish reproduction, development and growth are directly affected by temperature, investigating the regulatory mechanisms behind high temperature stress is helpful to construct a finer molecular network. In this study, we systematically analyzed the transcriptome and miRNA information of American shad (Alosa sapidissima) liver tissues at different cultivation temperatures of 24 ℃ (Low), 27 ℃ (Mid) and 30 ℃ (High) based on a high-throughput sequencing platform. Results The results showed that there were 1594 differentially expressed genes (DEGs) and 660 differentially expressed miRNAs (DEMs) in the LowLi vs. MidLi comparison group, 473 DEGs and 84 DEMs in the MidLi vs. HighLi group, 914 DEGs and 442 DEMs in the LowLi vs. HighLi group. These included some important genes and miRNAs such as calr, hsp90b1, hsp70, ssa-miR-125a-3p, ssa-miR-92b-5p, dre-miR-15a-3p and novel-m1018-5p. The DEGs were mainly enriched in the protein folding, processing and export pathways of the endoplasmic reticulum; the target genes of the DEMs were mainly enriched in the focal adhesion pathway. Furthermore, the association analysis revealed that the key genes were mainly enriched in the metabolic pathway. Interestingly, we found a significant increase in the number of genes and miRNAs involved in the regulation of heat stress during the temperature change from 24 °C to 27 °C. In addition, we examined the tissue expression characteristics of some key genes and miRNAs by qPCR, and found that calr, hsp90b1 and dre-miR-125b-2-3p were significantly highly expressed in the liver at 27 ℃, while novel-m0481-5p, ssa-miR-125a-3p, ssa-miR-92b-5p, dre-miR-15a-3p and novel-m1018-5p had the highest expression in the heart at 30℃. Finally, the quantitative expression trends of 10 randomly selected DEGs and 10 DEMs were consistent with the sequencing data, indicating the reliability of the results. Conclusions In summary, this study provides some fundamental data for subsequent in-depth research into the molecular regulatory mechanisms of A. sapidissima response to heat stress, and for the selective breeding of high temperature tolerant varieties.

Abstract The intelligent appearance quality classification method for Auricularia auricula is of great significance to promote this industry. This paper proposes an appearance quality classification method for Auricularia auricula based on the improved Faster Region-based Convolutional Neural Networks (improved Faster RCNN) framework. The original Faster RCNN is improved by establishing a multiscale feature fusion detection model to improve the accuracy and real-time performance of the model. The multiscale feature fusion detection model makes full use of shallow feature information to complete target detection. It fuses shallow features with rich detailed information with deep features rich in strong semantic information. Since the fusion algorithm directly uses the existing information of the feature extraction network, there is no additional calculation. The fused features contain more original detailed feature information. Therefore, the improved Faster RCNN can improve the final detection rate without sacrificing speed. By comparing with the original Faster RCNN model, the mean average precision (mAP) of the improved Faster RCNN is increased by 2.13%. The average precision (AP) of the first-level Auricularia auricula is almost unchanged at a high level. The AP of the second-level Auricularia auricula is increased by nearly 5%. And the third-level Auricularia auricula AP is increased by 1%. The improved Faster RCNN improves the frames per second from 6.81 of the original Faster RCNN to 13.5. Meanwhile, the influence of complex environment and image resolution on the Auricularia auricula detection is explored.

Abstract Ultrafine secondary marine aerosol (

Abstract Adipose tissue development begins in the fetal period, and continues to expand after birth. Dysregulation of adipose tissue during weaning may predispose individuals to lifelong metabolic disorders. However, the developmental remodeling of adipose tissue during weaning remains largely unexplored. Here we comprehensively compare the changes in mouse subcutaneous white adipose tissue from 7 days after birth to 7 days after weaning using single-cell RNA sequencing along with other molecular and histologic assays. We characterize the developmental trajectory of preadipocytes and indicate the commitment of preadipocytes with beige potential during weaning. Meanwhile, we find immune cells unique to weaning period, whose expression of extracellular matrix proteins implies potential regulation on preadipocyte. Finally, the strongest cell-cell interaction during weaning determined by the TGFβ ligand-receptor pairs is between preadipocytes and endotheliocytes. Our results provide a detailed and unbiased cellular landscape and offer insights into the potential regulation of adipose tissue remodeling during weaning.

Abstract Growing evidence indicates that extreme heat and rain may occur in succession within short time periods and cause greater impacts than individual events separated in time and space. Therefore, many studies have examined the impacts of compound hazard events on the social-ecological system at various scales. The definition of compound events is fundamental for such research. However, there are no existing studies that support the determination of time interval between individual events of a compound rainstorm and heatwave (CRH) event, which consists of two or more potentially qualifying component heatwave and rainstorm events. To address the deficiency in defining what individual events can constitute a CRH event, this study proposed a novel method to determine the maximum time interval for CRH events through the change in CRH event frequency with increasing time interval between individual events, using southern China as a case study. The results show that the threshold identified by the proposed method is reasonable. For more than 90% of the meteorological stations, the frequency of CRH events has reached a maximum when the time interval is less than or equal to the threshold. This study can aid in time interval selection, which is an important step for subsequent study of CRH events.

Abstract Background Liver disease and dementia are both highly prevalent and share common pathological mechanisms. We aimed to investigate the associations between metabolic dysfunction-associated fatty liver disease (MAFLD), metabolic dysfunction-associated steatotic liver disease (MASLD) and the risk of all-cause and cause-specific dementia. Methods We conducted a prospective study with 403,506 participants from the UK Biobank. Outcomes included all-cause dementia, Alzheimer’s disease, and vascular dementia. Multivariable Cox proportional hazards models were used for analyses. Results 155,068 (38.4%) participants had MAFLD, and 111,938 (27.7%) had MASLD at baseline. During a median follow-up of 13.7 years, 5,732 participants developed dementia (2,355 Alzheimer’s disease and 1,274 vascular dementia). MAFLD was associated with an increased risk of vascular dementia (HR 1.32 [95% CI 1.18–1.48]) but a reduced risk of Alzheimer’s disease (0.92 [0.84–1.0]). Differing risks emerged among MAFLD subtypes, with the diabetes subtype increasing risk of all-cause dementia (1.8 [1.65–1.96]), vascular dementia (2.95 [2.53–3.45]) and Alzheimer’s disease (1.46 [1.26–1.69]), the lean metabolic disorder subtype only increasing vascular dementia risk (2.01 [1.25–3.22]), whereas the overweight/obesity subtype decreasing risk of Alzheimer’s disease (0.83 [0.75–0.91]) and all-cause dementia (0.9 [0.84–0.95]). MASLD was associated with an increased risk of vascular dementia (1.24 [1.1–1.39]) but not Alzheimer’s disease (1.0 [0.91–1.09]). The effect of MAFLD on vascular dementia was consistent regardless of MASLD presence, whereas associations with Alzheimer’s disease were only present in those without MASLD (0.78 [0.67–0.91]). Conclusions MAFLD and MASLD are associated with an increased risk of vascular dementia, with subtype-specific variations observed in dementia risks. Further research is needed to refine MAFLD and SLD subtyping and explore the underlying mechanisms contributing to dementia risk.

Abstract Purpose Symptom assessment based on patient-reported outcome (PRO) can correlate with disease severity, making it a potential tool for threshold alerts of postoperative complications. This study aimed to determine whether shortness of breath (SOB) scores on the day of discharge could predict the development of post-discharge complications in patients who underwent lung cancer surgery. Methods Patients were from a study of a dynamic perioperative rehabilitation cohort of lung cancer patients focusing on patient-reported outcomes. Patients were assessed using the Perioperative Symptom Assessment Scale for Lung surgery (PSA-Lung). Logistic regression model was used to examine the potential association between SOB on the day of discharge and complications within 3 months after discharge. The post-discharge complications were taken as the anchor variable to determine the optimal cutpoint for SOB on the day of discharge. Results Complications within 3 months post-discharge occurred in 71 (10.84%) of 655 patients. Logistic regression analysis revealed that being female (OR 1.764, 95% CI 1.006–3.092, P