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Abstract Background Despite remarkable achievements in applying chimeric antigen receptor (CAR)-T cells to treat hematological malignancies, they remain much less effective against solid tumors, facing several challenges affecting their clinical use. We previously showed that multichain DNAX-activating protein (DAP) CAR structures could enhance the safety and efficacy of CAR-T cells when used against solid tumors. In particular, mesothelin (MSLN)-targeted CAR-T cell therapy has therapeutic potential in MSLN-positive solid tumors, including ovarian cancer and mesothelioma. Methods In vitro cell killing assays and xenograft model were utilized to determine the anti-tumor efficacy of MSLN targeting DAP-CAR-T cells and other CAR-T cells. ELISA and flow cytometry analysis were used to assess the cytokine secretion capacity and proliferation ability. Eight patients with MSLN expression were enrolled to evaluate the safety and efficacy of MSLN-DAP CAR-T cell therapy. Single-cell sequencing was performed to explore the dynamics of immune cells in patients during treatment and to identify the transcriptomic signatures associated with efficacy and toxicity. Results We found that multichain DAP-CAR formed by combining a natural killer cell immunoglobulin-like receptor truncator and DAP12 exhibited better cytotoxicity and tumor-killing capacity than other natural killer cell-activated receptors associated with DAP12, DAP10, or CD3Z. The safety and efficacy of MSLN-DAP CAR-T cell therapy in patients with ovarian cancer and mesothelioma were evaluated in a single-arm, open-label clinical trial (ChiCTR2100046544); two patients achieved partial response, while four patients had a stable disease status. Furthermore, single-cell sequencing analysis indicated that KT032 CAR-T cell infusion could recruit more immune cells and temporarily remodel the TME. Conclusions Our study highlights the safety and therapeutic efficacy of multiple-chain DAP-CAR-T cell therapy targeting MSLN to treat patients with ovarian cancer and mesothelioma. Trial registration ChiCTR.org.cn, ChiCTR2100046544 . May 21, 2021.

Abstract Background The importance of physical education in higher education is widely recognized, as it improves not only exercise attitudes and motor skills but also physical fitness, social skills, and academic performance. However, physical education courses in Chinese colleges and universities face various constraints, such as a shortage of teachers, limited teaching methods, and insufficient resources, resulting in low student motor skills, negative attitudes toward sports, and low participation rates. This study explores the effectiveness of a blended learning model, which integrates traditional face-to-face instruction with online learning components, in improving university students’ exercise attitudes and basketball skills. Methods The research was conducted in 2022 at Luoyang Normal University in China, utilizing a cluster randomized controlled trial (CRCT) with 78 healthy first-year university students. Participants were randomly assigned to either the experimental group (blended learning) or the control group (traditional learning), and the intervention lasted 16 weeks. Exercise attitudes were assessed via the Exercise Attitude Scale, whereas basketball skills were evaluated via set shot and half-court dribbling and shooting tests. Results Both instructional models improved students’ exercise attitudes and basketball skills; however, the blended learning model demonstrated significantly superior outcomes. Effect sizes (d) ranging from 0.57 to 1.92 indicated that the experimental group showed greater improvements in behavior attitude, target attitude, behavior cognition, behavior intention, emotional experience, behavior control, and subjective standards. In basketball skills, the experimental group outperformed the control group in set shots (d = 0.56) and half-court dribbling and shooting (d = 0.46). Conclusion Compared with traditional methods, blended learning significantly enhances university students’ exercise attitudes and basketball skills. Future research should explore the long-term effects and underlying mechanisms of blended learning in physical education, involving larger and more diverse samples to validate these findings.

In order to study the distribution law of gas residual content in coal seam under long borehole extraction, the formula of long borehole gas extraction model was deduced based on negative pressure attenuation effect. The gas-air model was established by COMSOL simulation software, and the distribution law of gas residual content in coal seam under long borehole extraction was analyzed. The results show that the extraction negative pressure presents a logarithmic function distribution, and the negative pressure at the bottom of the hole is the smallest. As the depth of the borehole increases, the attenuation of the extraction negative pressure is smaller. Due to the phenomenon of negative pressure attenuation in drilling, the horizontal and vertical residual gas content of drilling presents logarithmic function distribution. At the end of the sealing section, the coal body is subjected to the pressure of the sealing material, which makes the coal body compacted, the porosity decreases, the gas migration in the vicinity is more difficult, and the gas flow resistance increases, resulting in a “lag” phenomenon in the gas content change at the end of the sealing section. By measuring the residual gas content of coal seams at different depths of 1# and 2# boreholes in Linhua Coal Mine, Guizhou, the logarithmic function relationship between sampling depth and residual gas content was obtained. The fitting degrees are 0.943 0 and 0.957 2, respectively, which were consistent with the theoretical analysis results.

Abstract Background The assembly of the rhizosphere community, even the diazotroph community, is mainly shaped by soil environmental factors (including soil climate and physiochemical characteristics) and plant selection. To better understand the driving forces on the active overall and nitrogen-fixing bacterial community compositions, we characterized the communities of tobacco rhizosphere soil collected from three sampling sites with a large geographic scale (> 600 km). Results The results indicate that the diversity and community composition of the overall bacterial and diazotroph communities are obviously differed according to the sampling sites. Still, no significant difference is found between the communities in rootzone and rhizosphere samples. Climate variables including mean annual precipitation (MAP) and mean annual temperature (MAT), soil physiochemical characteristics including available nitrogen (AN), available potassium (AK) and pH are main factors that affect the bacterial and diazotroph community structures in the three sampling sites. Furthermore, MAP and MAT, AN and available phosphorus (AP), total nitrogen (TN) and organic carbon (OC), AK and electrical conductivity (EC) showed similar effects, but pH showed independent effect on the composition of the overall bacteria and diazotroph communities. However, the alpha diversity indices of active overall and nitrogen-fixing bacteria in the rhizosphere are obviously higher than in the rootzone samples, and no significant differences are observed among different sampling sites. Proteobacteria is the predominant active phylum of all samples for overall and nitrogen-fixing bacteria. Escherichia-Shigella, Achromobacter, Streptomyces and Sphingomonas are the dominant active bacterial genera, and Bradyrhizobium, Skermanella and Extensimonas are dominant active nitrogen-fixing bacteria genera in rhizosphere. Furthermore, the high active abundance of Escherichia-Shigella but low abundance of Ralstonia in all three sampling sites indicate high root-knot nematode infection and low wilt disease endemic risk. Conclusion These results indicate that soil environmental factors contribute more to the tobacco rhizosphere bacterial community assemblage, but the rhizosphere contributes more to the diversity of active overall bacteria and nitrogen-fixing bacteria in the community. Our study provides novel knowledge for the assemble of rhizosphere bacterial and active bacteria communities across a large geographical scale.

Abstract Objectives The research aimed to provide the most recent and comprehensive analysis and evidence update comparing outcomes in neonatal encephalopathy (NE) based on different glycemia levels. Patients and methods A comprehensive search of Cochrane, PubMed, Embase, Web of Science, CNKI, and Wanfang databases was conducted until September 2023. The purpose was to identify research that examined the effects of hyperglycemia, hypoglycemia, and normoglycemia on NE outcomes. The hyperglycemic, normoglycemic and hypoglycemic group were compared. Outcomes measured were mortality, abnormal MRI, hearing or visual unfavorable outcomes, neurodevelopmental delay, cerebral palsy, and all unfavorable outcomes. Results Thirteen literatures comprising 2,427 participants (1,233 with normoglycemia, 835 with hyperglycemia, and 359 with hypoglycemia) were considered. Pooled analysis showed more overall adverse outcomes, higher mortality and worse hearing or visual outcomes in the hyperglycemic and hypoglycemic group compared to the normoglycemic group. There was no notable distinction found in abnormal MRI and cerebral palsy among all groups. The hypoglycemic group exhibited greater neurodevelopmental delay than normoglycemia. Conclusions Maintaining normal blood glucose levels in neonates with NE can help reduce the risk of adverse consequences such as hearing and visual impairment.

In this paper, the effects of Hf addition on the mechanical properties, electrical conductivity and microstructure of Cu-Sn-P alloy were investigated. The results show that the Hf addition can enhance the mechanical properties and electrical conductivity of Cu-Sn-P alloy. The alloy with 0.05 wt% Hf exhibits the best comprehensive performance with yield strength of 625 MPa, tensile strength of 661 MPa and electrical conductivity of 16.8 %IACS. Compared with the Cu-Sn-P alloy without Hf addition, the yield strength and tensile strength are increased by 8.4% and 7.8%, and the electrical conductivity is increased by 24.4%. The increase in the strength of Hf-added alloy can be attributed to the synergistic effect of multiple strengthening mechanisms, including fine grain strengthening, twin strengthening, dislocation strengthening, precipitation strengthening and Σ3n (n = 1, 2, 3) grain boundary strengthening. Moreover, the Hf-P precipitates can be observed in the Hf-added alloy. According to the amount of Hf addition, these precipitates can manifest as the fine HfP2 phase and the coarse HfP phase. The formation of Hf-P precipitates contributes to the precipitation strengthening and the purification of Cu matrix, thus contributing to the improvement of strength and conductivity.

Coal seam water injection is widely used for coal seam gas control, and the key to its effectiveness in controlling gas lies in the wetting effect of water on coal body. However, the gas in coal seriously interferes with the wetting effect of water on coal. This paper uses a self-developed coal and water contact angle testing equipment under gas atmosphere and a self-developed water’s surface tension testing software under gas atmosphere to study the wetting parameters of coal and water interface under gas atmosphere, elucidating the wetting characteristics of coal and water interface under gas atmosphere and revealing its influencing mechanism. The results show that the surface tension of water, surface energy of coal, and adhesion work gradually decrease with the increase of gas pressure in a gas atmosphere. However, the coal and water contact angle and coal and water interface energy gradually increase with the increase of gas pressure, which implies a decrease in the wetting effect of water on coal. A molecular structure model of anthracite coal has been established based on the industrial analysis, elemental analysis, and micro spectral analysis of coal. The molecular formula of coal can be described by C99H54N2O3S. The bridge carbon ratio of the coal molecular model is 0.61, which is consistent with the bridge carbon ratio in the 13C-NMR spectrum. In the micro wetting system of coal water under gas atmosphere, with the increase of gas pressure, the adsorption degree of water molecules weakens, the degree of gas displacement in coal decreases, the diffusion coefficient of methane molecules decreases, the dispersion degree of water molecules increases, the aggregation degree of water molecules weakens, and the diffusion coefficient of water molecules increases. The research results lay a theoretical foundation for revealing the mechanism of wetting coal containing gas by coal seam water injection.

Abstract Hyperspectral image (HSI) data has a wide range of valuable spectral information for numerous tasks. HSI data encounters challenges such as small training samples, scarcity, and redundant information. Researchers have introduced various research works to address these challenges. Convolution Neural Network (CNN) has gained significant success in the field of HSI classification. CNN’s primary focus is to extract low-level features from HSI data, and it has a limited ability to detect long-range dependencies due to the confined filter size. In contrast, vision transformers exhibit great success in the HSI classification field due to the use of attention mechanisms to learn the long-range dependencies. As mentioned earlier, the primary issue with these models is that they require sufficient labeled training data. To address this challenge, we proposed a spectral-spatial feature extractor group attention transformer that consists of a multiscale feature extractor to extract low-level or shallow features. For high-level semantic feature extraction, we proposed a group attention mechanism. Our proposed model is evaluated using four publicly available HSI datasets, which are Indian Pines, Pavia University, Salinas, and the KSC dataset. Our proposed approach achieved the best classification results in terms of overall accuracy (OA), average accuracy (AA), and Kappa coefficient. As mentioned earlier, the proposed approach utilized only 5%, 1%, 1%, and 10% of the training samples from the publicly available four datasets.

Abstract Parkinson’s disease (PD) and Dementia with Lewy Bodies (DLB) are neurodegenerative disorders characterized by the accumulation of α-synuclein aggregates. α-synuclein forms droplets via liquid-liquid phase separation (LLPS), followed by liquid-solid phase separation (LSPS) to form amyloids, how this process is physiologically-regulated remains unclear. β-synuclein colocalizes with α-synuclein in presynaptic terminals. Here, we report that β-synuclein partitions into α-synuclein condensates promotes the LLPS, and slows down LSPS of α-synuclein, while disease-associated β-synuclein mutations lose these capacities. Exogenous β-synuclein improves the movement defects and prolongs the lifespan of an α-synuclein-expressing NL5901 Caenorhabditis elegans strain, while disease-associated β-synuclein mutants aggravate the symptoms. Decapeptides targeted at the α-/β-synuclein interaction sites are rationally designed, which suppress the LSPS of α-synuclein, rescue the movement defects, and prolong the lifespan of C. elegans NL5901. Together, we unveil a Yin-Yang balance between α- and β-synuclein underlying the normal and disease states of PD and DLB with therapeutical potentials.

Abstract Background This study aims to identify risk factors associated with Methicillin-resistant Staphylococcus aureus (MRSA) infection in children diagnosed with acute osteomyelitis (AO) and to elucidate the laboratory characteristics of these MRSA-infected children to enhance early targeted therapeutic interventions. Methods We conducted a retrospective analysis involving 123 children with acute osteomyelitis treated at our hospital. Upon admission, we measured white blood cell (WBC) counts, C-reactive protein (CRP) levels, erythrocyte sedimentation rates (ESR), and platelet counts. Patients were categorized into two groups: the non-MRSA group (n = 73) and the MRSA group (n = 50), with values assigned as follows (non-MRSA group = 0, MRSA group = 1). Results The MRSA group had a significantly higher average age compared to the non-MRSA group (P 10.95 × 10^9/L, CRP > 49.56 µg/mL, age > 3.5 years, and the absence of suppurative arthritis suggests a heightened risk of MRSA infection.

Abstract Background Mitochondrial dysfunction is one of the hallmarks of aging and a leading contributor to sarcopenia. Nutrients are essential for improving mitochondrial function and skeletal muscle health during the aging process. Betaine is a nutrient with potential muscle‐preserving properties. However, whether and how betaine could regulate the mitochondria function in aging muscle are poorly understood. We aimed to explore the molecular target and underlying mechanism of betaine in attenuating the age‐related mitochondrial dysfunction in skeletal muscle. Methods Young mice (YOU, 2 months), old mice (OLD, 15 months), and old mice with betaine treatment (BET, 15 months) were fed for 12 weeks. The effects of betaine on muscle mass, strength, function, and subcellular structure of muscle fibres were assessed. RNA sequencing (RNA‐seq) was conducted to identify the molecular target of betaine. The impacts of betaine on mitochondrial‐related molecules, superoxide accumulation, and oxidative respiration were examined using western blotting (WB), immunofluorescence (IF) and seahorse assay. The underlying mechanism of betaine regulation on the molecular target to maintain mitochondrial function was investigated by luciferase reporter assay, chromatin immunoprecipitation and electrophoretic mobility shift assay. Adenoassociated virus transfection, succinate dehydrogenase staining (SDH), and energy expenditure assessment were performed on 20‐month‐old mice for validating the mechanism in vivo. Results Betaine intervention demonstrated anti‐aging effects on the muscle mass (P = 0.017), strength (P = 0.010), and running distance (P = 0.013). Mitochondrial‐related markers (ATP5a, Sdha, and Uqcrc2) were 1.1‐ to 1.5‐fold higher in BET than OLD (all P ≤ 0.036) with less wasted mitochondrial vacuoles accumulating in sarcomere. Bioinformatic analysis from RNA‐seq displayed pathways related to mitochondrial respiration activity was higher enriched in BET group (NES = −0.87, FDR = 0.10). The quantitative real time PCR (qRT‐PCR) revealed betaine significantly reduced the expression of a novel mitochondrial regulator, Mss51 (−24.9%, P = 0.002). In C2C12 cells, betaine restored the Mss51‐mediated suppression in mitochondrial respiration proteins (all P ≤ 0.041), attenuated oxygen consumption impairment, and superoxide accumulation (by 20.7%, P = 0.001). Mechanically, betaine attenuated aging‐induced repression in Yy1 mRNA expression (BET vs. OLD: 2.06 vs. 1.02, P = 0.009). Yy1 transcriptionally suppressed Mss51 mRNA expression both in vitro and in vivo. This contributed to the preservation of mitochondrial respiration, improvement for energy expenditure (P = 0.008), and delay of muscle loss during aging process. Conclusions Altogether, betaine transcriptionally represses Mss51 via Yy1, improving age‐related mitochondrial respiration in skeletal muscle. These findings suggest betaine holds promise as a dietary supplement to delay skeletal muscle degeneration and improve age‐related mitochondrial diseases.

The success of deep supervised learning in Synthetic Aperture Radar (SAR) Automatic Target Recognition (ATR) relies on a large number of labeled samples. However, label noise often exists in large-scale datasets, which highly influence network training. This study proposes loss curve fitting-based label noise uncertainty modeling and a noise uncertainty-based correction method. The loss curve is a discriminative feature to model label noise uncertainty using an unsupervised fuzzy clustering algorithm. Then, according to this uncertainty, the sample set is divided into different subsets: the noisy-label set, clean-label set, and fuzzy-label set, which are further used in training loss with different weights to correct label noise. Experiments on the Moving and Stationary Target Acquisition and Recognition (MSTAR) dataset prove that our method can deal with varying ratios of label noise during network training and correct label noise effectively. When the training dataset contains a small ratio of label noise (40%), the proposed method corrects 98.6% of these labels and trains the network with 98.7% classification accuracy. Even when the proportion of label noise is large (80%), the proposed method corrects 87.8% of label noise and trains the network with 82.3% classification accuracy.

Underwater concrete structure crack detection and structural health condition assessment based on image processing is a challenging task. The complex underwater environment and severe image degradation seriously affect the accuracy of crack detection. To solve these problems, a monocular vision and image-enhanced fractal-based fractal science based on computer vision and image processing techniques are proposed to carry out a non-contact detection study of underwater concrete cracks. In this study, a four-level structural health condition was established to assist in underwater crack measurement and safety assessment. The box-counting method was used as a practical tool to calculate the fractal dimension. To verify the effective distance of the algorithm, three distances of 0.5 m,0.8 m, and 1.2 m were set. The results show that the method proposed in this study can effectively detect cracks in submerged concrete members within 0.6 m and help managers correctly determine the health of the structure using the fractal dimension.

For the detection of ferritin, this work engineered an electrochemical immunosensor by functionalizing multi-walled carbon nanotubes (MWCNTs) and integrating them into a screen-printed carbon electrode (SPCE) platform. Under optimal conditions (pH 7.4, antibody concentration 10 μg/mL, incubation time 30 min), the developed immunosensor exhibited a linear relationship between the electrochemical signal and ferritin concentrations spanning 1–500 ng/mL. Notably, it demonstrated an impressive ability to detect ferritin at exceptionally low levels, with a limit of detection reaching 0.3 ng/mL. The immunosensor demonstrated high selectivity, good reproducibility (RSD = 3.2 %, n = 5), and stability (87.3 % of initial response after 14 days at 4°C). The immunosensor was used to sensing ferritin in serum and good agreement with the commercial ELISA method (relative error < 5 %). The proposed sensor shows promise as a analytical approach for early diagnosis of lymphoma and point-of-care testing.

This paper describes a three-dimensional and comprehensive method for completing the northern extension of the Maoshan fracture zone from deep to shallow. Gravity field data interpretation and geomagnetic survey were used to initially locate the rupture, followed by shallow seismic survey for precise positioning, and finally the upper rupture point was captured and its Quaternary activities were investigated according to the method of joint geologic profile exploration with small spaced drill holes across the rupture point. Research has found: ① The Maoshan fracture zone continues to extend northward into the urban area of Zhenjiang, and the northern extension of the Maoshan fracture zone cuts at least to the mid-crustal region. ② The shallow part of the northern extension of the Maoshan fracture zone shows normal faulting characteristics, with an inclination to the east and a strike to the north-east, an apparent dip of about 60°, and an apparent break distance of about 3～5 m. ③ The results of the joint geologic profile of the boreholes show that the bedrock surface on both sides of the fracture point has a small difference, and the overlying Quaternary strata do not have any large undulation and do not have any obvious signs of Quaternary activity, so it is comprehensively judged that the northern extension of the Maoshan fracture zone is a pre-Quaternary fracture. This study preliminarily suggests that the Maoshan fault may be geospatially linked to two significant seismic events in the history of the Jiangsu landmass. This finding provides a new perspective for further research on the seismogenic tectonic features and seismic activity patterns in the region, and may inspire future related studies.

Abstract Objective Pulmonary infection is one of the leading causes of death in patients with ANCA-associated vasculitis (AAV). It is sometimes difficult to differentiate pulmonary infection from pulmonary involvement of vasculitis in AAV patients. Fiberoptic bronchoscopy and bronchoalveolar lavage fluid (BALF) assays are useful diagnostic methods. In addition to conventional microbiological tests (CMTs), metagenomic next-generation sequencing (mNGS) facilitates rapid and sensitive detection of various pathogens. The current study aimed to evaluate the advantages of additional BALF mNGS in the management of pulmonary infection in AAV patients. Methods 27 patients with active AAV and suspected pulmonary infection whose BALF samples were tested by mNGS and CMTs and 17 active AAV patients whose BALF were tested by CMTs alone were retrospectively recruited. The results of microbiological tests, and adjustments of treatment following BALF mNGS, were described. The durations of antimicrobial treatment and in-hospital mortality in patients were compared. Results Among the 27 patients whose BALF samples were tested by mNGS, 25.9% of patients did not have evidence of pathogenic microorganism in their BALF samples, 55.6% had polymicrobial infections, including bacteria, fungi and viruses. Of these 27 patients, 40.7% did not have evidence of pathogenic microorganism in their BALF or serum samples according to CMTs. Patients in the BALF mNGS/CMT group received a significantly shorter duration of antibacterial and total antimicrobial treatment than patients in the CMT alone group (17.3 ± 14.7 vs. 27.9 ± 19.0 days, P = 0.044; 18.9 ± 15.0 vs. 29.5 ± 17.7 days, P = 0.040, respectively). Fewer patients in the BALF mNGS/CMT group died than in the CMT alone group (4/27 vs. 7/17, P = 0.049). Conclusion Compared with CMT alone, additional mNGS tests may shorten the duration of antimicrobial treatment and possibly decrease death from severe infection by providing precise and quick diagnosis of infection.

Abstract Background Larch is an important timber tree species. The traditional methods of tree genetic breeding have been progressing slowly. It is necessary to carry out gene function analysis and genetically modified breeding research. The NAC transcription factor family is a plant-specific transcription factor family with various biological functions, as shown in recent research. However, there are few studies on the NAC gene among gymnosperm coniferous species. Results LoNAC3 with complete cds was identified and isolated from the cDNA of Larix olgensis based on transcriptome data. The cDNA length of LoNAC3 is 1185 bp, encoding 394 amino acids, with a conserved NAM domain located at the N-terminus, and subcellular localization in the nucleus. The results of real-time quantitative PCR analysis showed that at different growth stages and in different tissues of L. olgensis, the relative expression level of LoNAC3 was highest in the needles. After drought, salt, alkali stress and hormone treatment, expression was induced to different degrees. The expression level of LoNAC3 was significantly increased under drought and salt conditions. The relative expression level changed under methyl jasmonate (MeJA) and abscisic acid (ABA) treatment. By observing the phenotype of overexpressed LoNAC3 tobacco, it was found that overexpressed tobacco is shorter and blooms earlier than wild-type tobacco. Under abiotic stress, LoNAC3 overexpressed tobacco has lower germination rates and poorer growth status. Transgenic tobacco under stress treatment has a higher malondialdehyde (MDA) content than wild-type tobacco, while peroxidase (POD) activity is lower than wild-type tobacco. Conclusions Through the analysis of LoNAC3 sequence and promoter expression, it can be concluded that LoNAC3 is involved in the drought and salt stress response processes of L. olgensis, and is induced by ABA and MeJA expression. Overexpression of LoNAC3 leads to stunted tobacco growth and negatively regulates its tolerance to drought and salt stress through the reactive oxygen species pathway. The preliminary analysis of the expression pattern and function of the LoNAC3 can provide a theoretical basis and high-quality materials for genetic improvement of larch in later stages.

Abstract Psoriasis is a chronic, relapsing, and refractory immune-mediated skin disease with the etiology and pharmaceutical targets remaining unsatisfactorily addressed. Topical herbal-derived compounds, such as tryptanthrin (Tryp), have been considered as an alternative therapy for psoriasis due to their lower costs and fewer side effects compared to other therapies. However, the effectiveness of topically administered drugs is substantially limited by the thickened pathological skin barrier and the low bioavailability of drugs in the deeper layers of the lesion. Ethosomes, being a novel phospholipid-based vesicle system with high content of ethanol, have been implicated in enhancing topical drug absorption and restoring psoriatic lesions. In this study, taking advantages of ethosomes as a soft and malleable drug carrier, we constructed the Tryp-loaded ethosome (Tryp-ES) through a one-step microfluidics-based technique. The optimal formulation of Tryp-ES was achieved by adding amino-acid-derived surfactant sodium lauroyl glutamate, and Tryp-ES exhibited homogeneous particle size and favorable stability at room temperature. In vitro evaluations showed that Tryp of Tryp-ES could be easily internalized into cells and accumulated in cell nuclei, hence inhibited the abnormally proliferated keratinocytes by inducing apoptosis. In vivo and in vitro assessment using psoritic skin of mice revealed that Tryp-ES had preferred skin retention and permeation of loaded drugs within the initial 1 h of topical administration, which could be attributed to transient disintegrations of cell membranes by ethosomes, thus improved cellular fluidity and permeability. Notably, a synergistic effect of ethosomes and Tryp was found in psoriatic mice. Tryp-ES-treated mice showed substantially ameliorated symptoms of psoriasis and reduced pathological alterations due to hyperplasia, inflammation and angiogenesis, without detectable local or systemic toxicities. Interestingly, lipidomics analysis confirmed that the supplementation of phospholipids, as in the form of ethosome vehicles, was an alterantive strategy to relieve psoriatic pathologies. Taken together, this study provides a novel impact for ethosomal topical delivery of Tryp and underlines their potential as an effective therapy for the management of psoriasis.

Abstract Background The purpose of this study was to explore the expression of miR-665 in acute myocardial infarction (AMI) and evaluate its significance in the diagnosis and prognosis of AMI. Methods 100 patients with AMI were selected as the study group and 80 healthy subjects were chosen as the control group. The levels of miR-665 were detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR) in the two groups. The diagnostic value of miR-665 expression level in AMI was analyzed by the receiver operator characteristic (ROC) curve. Kaplan-Meier curve and Cox regression were used to evaluate the predictive value of miR-665 for major adverse cardiovascular events (MACEs) in patients with AMI within 30 days after percutaneous coronary intervention (PCI). Results The serum miR-665 level of the study group was significantly lower than that of the control group. The level of miR-665 was significantly correlated with clinical indicators of patients with AMI. ROC curve showed that miR-665 has a high diagnostic value for AMI. Survival analysis showed that Gensini score and miR-665 were independent risk factors for the occurrence of MACEs within 30 days after PCI in patients with AMI. Conclusions Abnormal decrease of serum miR-665 expression level in patients with AMI may increase the risk of MACEs occurrence after PCI.

Abstract Background Human papillomavirus (HPV) infection significantly contributes to the global cancer burden. Understanding the factors influencing male clinical interns’ willingness to promote HPV vaccination is crucial for developing effective public health strategies in China. Methods This study employed a stratified random sampling method to select 1,980 male clinical interns from five provinces in China between January and March 2024. Data were collected on participants’ demographic characteristics, HPV-related clinical experience, and knowledge. The Theory of Planned Behavior framework, encompassing attitudes, subjective norms, and perceived behavioral control, was used to examine factors influencing the willingness to promote the HPV vaccine. Logistic regression analyses were conducted to identify factors associated with the willingness to promote the HPV vaccine. Results Among the respondents, 72.29% were willing to encourage others to receive the HPV vaccine. Significant factors influencing this willingness included older age (OR = 3.065, P ≤ 0.001), higher monthly household income (OR = 1.449, P = 0.025), participation in the diagnosis and treatment of HPV-related diseases (OR = 3.458, P ≤ 0.001), positive attitude towards the vaccine (OR = 13.503, P = 0.004), and strong perceived behavioral control (OR = 2.364, P = 0.006). Conclusion This study highlights the critical role of practical experience and targeted education in promoting HPV vaccination among male clinical interns in China. Enhancing the training and education of this group is essential for improving HPV vaccine advocacy and supporting public health efforts to reduce HPV-related diseases.

Abstract Background The triglyceride-glucose (TyG) index is recognized as a robust indicator for evaluating insulin resistance (IR). Despite the well-documented anti-aging biological functions of Klotho protein, its correlation with the TyG index remains unexplored. Methods A cross-sectional analysis was conducted involving participants from the National Health and Nutrition Examination Surveys (NHANES) 2007–2016. The TyG index was computed using laboratory data, while serum Klotho concentrations was determined using ELISA kit. After adjusting potential confounding variables, multivariate regression models were employed to evaluate the association between the TyG index and Klotho protein levels among middle-aged and elderly females and males separately. Additionally, smooth curve fitting and segmented regression model were applied to investigate potential threshold effects and identify the inflection point. Results A total of 6,573 adults qualified for inclusion, comprising 3,147 (47.88%) males and 3,426 (52.12%) females. Multivariate regression analysis revealed that females with a higher TyG index exhibited significantly lower serum Klotho concentrations (β=-83.41, 95% CI: -124.23 to -42.60, P

Abstract Objective The university period is a critical stage of personal development, and improving the physical fitness of university students is crucial to their academic performance, quality of life, and future. However, in recent years, the physical fitness level of Chinese university students has shown a decreasing trend. This study aimed to investigate the effects of a blended learning model on the physical fitness of Chinese university students through a 16-week intervention. Methods A total of 78 first-year students from a public university in Henan Province were recruited for this study via a cluster randomized controlled trial (CRCT) design. The participants were divided into an experimental group (blended learning) and a control group (traditional learning). The intervention lasted for 16 weeks, and physical fitness indices such as body mass index (BMI), lung capacity, sit and reach, pull-ups/sit-ups, standing long jumps, 50-meter runs, and 1000/800-meter runs were measured before and after the intervention. Statistical analyses were conducted via generalized estimating equation (GEE) modeling, with the significance level set at P

Recently, researchers in the road field are focusing on the development of green asphalt materials with lower emission of volatile organic compounds (VOCs). The characterization methodology of asphalt VOCs and the influencing factors on VOCs release have always been the basic issue of asphalt VOCs emission reduction research. Researchers have proposed a variety of asphalt VOCs characterization methodologies, which also have mutually irreplaceable characteristics. Asphalt VOCs volatilization is affected by many factors. In this study, asphalt VOCs characterization methodologies were summarized, including their advantages, disadvantages, characteristics and applicable requirements. Subsequently, the influencing factors of VOCs release, such as asphalt types and environment conditions, are summarized to provide theoretical support for the emission reduction research. The classification and mechanism of newly-development asphalt VOCs emission reduction materials are reviewed. The reduction efficiencies are also compared to select better materials and put forward the improvement objective of new materials and new processes. In addition, the prospects about development of VOCs release mechanism of asphalt materials during the full life cycle and feasibility research of high-efficiency composite emission reduction materials in the future were put forward.

Background: Long-term physical inactivity probably leads to a co-existence of osteoporosis and sarcopenia which result in a high risk of falls, fractures, disability and even mortality. However, universally applicable and feasible approaches are lacking in the concurrent treatment of osteoporosis and sarcopenia. In this study, we evaluated the effect of strontium zinc silicate bioceramic (SZS) extract on osteoporosis and sarcopenia and explored its underlying mechanisms. Methods: Hindlimb osteoporosis and sarcopenia were established in a tail-suspended rat model. The bones were conducted μCT scanning, histological examination, and gene expression analysis, and the muscles were conducted histological examination and gene expression analysis. In vitro, the effect of SZS extract on osteoblasts was determined by alizarin red S staining, immunofluorescence and qPCR. Similarly, the effect of SZS extract on myoblasts was determined by immunofluorescence and qPCR.. At last, the role of Piezo1 and the change of intracellular calcium ion (Ca2+) were explored through blockading the Piezo1 by GsMTx4 in MC3T3-E1 and C2C12 cells, respectively. Results: We found that SZS extract could concurrently and efficiently prevent bone structure deterioration, muscle atrophy and fibrosis in hind limbs of the tail-suspended rats. The in vivo study also showed that SZS extract could upregulate the mRNA expression of Piezo1, thereby maintaining the homeostasis of bones and muscles. In vitro study demonstrated that SZS extract could promote the proliferation and differentiation of MC3T3-E1 and C2C12 cells by increasing the intracellular Ca2+ in a Piezo1-dependent manner. Conclusion: This study demonstrated that SZS extract could increase Piezo1-mediated intracellular Ca2+, and facilitate osteogenic differentiation of osteoblast and myogenic differentiation of myoblasts, contributing to alleviation of osteoporosis and sarcopenia in a tail-suspended rat model. The translational potential of this article: The current study might provide a universally applicable and efficient strategy to treat musculoskeletal disorders based on bioactive ceramics. The verification of the role of Piezo1-modulated intracellular Ca2+ during osteogenesis and myogenesis provided a possible therapeutic target against mechanical related diseases.

An in-depth understanding of the bimodal scale particle reinforced composites, including the particle content and size, phase constitution and distribution, and their effects on mechanical properties and deformation mechanisms, is essential to advance the study of high performance high entropy alloys (HEAs). In this study, the bimodal-sized (nano + micron)(N + M)-Al2O3P/CoCrFeMnNi reinforced composites and monomadal-sized micron(M)-Al2O3P/CoCrFeMnNi reinforced composites were successfully fabricated using a two-step ball milling process in conjunction with spark plasma sintering (SPS) technology. Results showed that the Al2O3P/CoCrFeMnNi composites primarily consisted of fcc structure, with Al2O3 and MnAl2O4 as secondary phases. The M-Al2O3P reinforced composites contained obvious heterogeneous structure while (N + M)-Al2O3P reinforced composites exhibited a multi-scale grain structure comprising of double-sized reinforcement and multiple-sized matrix grains. The yield strength (YS) of bimodal-size particle reinforced composites was higher than that of monomadal particle reinforced composites. For example, the YS of (N-5)/(M − 5) and (N-5)/(M − 10) composites was 117% and 133% higher than that of HEA, respectively. Intriguingly, (N + M)-Al2O3P reinforced composites effectively addressed the issue of reduced material strength caused by a high concentration of particles with a monomadal size. Moreover, the composites of (N-5)/(M − 5) and (N-5)/(M − 10) with a high content of lightweight Al2O3P effectively contributed to the reduction in density of HEA, exhibiting a decrease by 11% and 17% compared to pure HEA, respectively.

Hirschsprung's disease (HSCR) is a congenital disorder characterized by the absence of ganglion cells in the colon, leading to various intestinal complications. The etiology of HSCR stems from complex genetic and environmental interactions, of which the intricate roles of non-coding RNAs (ncRNAs) are a key area of research. However, the roles of ncRNAs in the pathogenesis of HSCR have not been fully elucidated. In order to understand the variety of symptoms caused by HSCR and develop new therapeutic approaches, it is essential to understand the underlying biological genetic basis of HSCR. This review presents a comprehensive overview of the current understanding regarding the involvement of ncRNAs in HSCR, including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs). Additionally, it provides a summary of the molecular mechanisms through which ncRNAs regulate the expression of genes related to the proliferation, migration, and differentiation of intestinal neural crest cells, thereby contributing to the advancement of HSCR research.

Cyclic dinucleotides (CDNs) are critical adjuvants in antiviral vaccines and cancer immunotherapy, primarily through the activation of the cGAS-STING signaling pathway. Evaluating the immune responses triggered by CDNs is essential for the development of effective adjuvants. In this study, we performed a comparative transcriptome analysis to characterize the immune responses elicited by the recently identified nuclease-resistant Drosophila and bacterial CDN, 3’2’-cGAMP, in mammalian immune cells. We detected a robust induction of innate immune gene signature following 3’2’-cGAMP stimulation in digitonin-permeabilized mouse primary macrophages, comparable to the response observed with the canonical mammalian CDN, 2’3’-cGAMP. STING deficiency remarkably reduced 3’2’-cGAMP-induced phosphorylation of TBK1 and IRF3 and the induction of IFN-β, indicating that 3’2’-cGAMP signaling-mediated immune responses were mainly STING dependent. In comparison to 2’3’-cGAMP signaling, 3’2’-cGAMP signaling preferentially elicited many STING-dependent genes involved in transcription and nucleosome positioning and assembly in the nucleus, which are likely associated with several enriched pathways, including cellular senescence, HDACs deacetylate histones, and epigenetic regulation of gene expression. The integrative analysis further revealed that 3’2’-cGAMP signaling preferentially induced genes were associated with autoimmune disease-related processes, suggesting a potential side effect that requires monitoring when used as an adjuvant. In conclusion, this study provides the first transcriptional landscape of 3’2’-cGAMP signaling in mammals and reveals the immune response characteristics and potential side effects mediated by 3’2’-cGAMP signaling. These findings may aid in the development of 3’2’-cGAMP-based adjuvants for antiviral vaccines and cancer immunotherapy.

Argonaute proteins (Agos) represent a highly conserved family of proteins prevalent in all domains of life and have been implicated in various biological processes. Based on the domain architecture, Agos can be divided into long Agos and short Agos. While long Agos have been extensively studied over the past two decades, short Agos, found exclusively in prokaryotes, have recently gained attention for their roles in prokaryotic immune defence against mobile genetic elements, such as plasmids and phages. Notable functional and structural studies provide invaluable insights into the underlying molecular mechanisms of representative short Ago systems. Despite the diverse domain arrangements, short Agos generally form heterodimeric complexes with their associated effector proteins, activating the effector’s enzymatic activities upon target detection. The activation of effector proteins in the short Ago systems leads to bacterial cell death, a mechanism of sacrificing individuals to protect the community.

Nosema ceranae, a parasite that parasitizes and reproduces in the gut of honeybees, has become a serious threat to the global apiculture industry. RNA interference (RNAi) technology can be used to inhibit N. ceranae growth by targeting silencing the thioredoxin reductase (TrxR) in N. ceranae. However, suitable carriers are one of the reasons limiting the application of RNAi due to the easy degradation of dsRNA in honeybees. As a vesicle composed of a lipid bilayer, liposomes are a good carrier for nucleic acid delivery, but studies in honeybees are lacking. In this study, liposomes were used for double-stranded RNA (dsRNA) dsTrxR delivery triggering RNAi to inhibit the N. ceranae growth in honeybees. Compared to naked dsTrxR, liposome-dsTrxR reduced N. ceranae numbers in the midgut and partially restored midgut morphology without affecting bee survival and gut microbial composition. The results of this study confirmed that liposomes could effectively protect dsRNA from entering the honeybee gut and provide a reference for using RNAi technology to suppress honeybee pests and diseases.

Abstract Understanding public awareness of environmental problems is vital for effectively formulating sustainable policies. This paper aims to investigate the impacts of two perspectives—external air pollution and individual health status—on public awareness by leveraging panel data from two waves of the China Family Panel Studies (CFPS) conducted between 2018 and 2020. The model integrates provincial-level PM2.5 concentration indicators and SO2, PMs, and NOx emissions. The results reveal a significantly positive correlation between air pollution and public awareness of environmental problems in China. Additionally, this study examines the impact of self-assessed health shock by categorizing it into worse and better health. The influence of better health is insignificant. Conversely, when individuals experience worse health, they may perceive it as a psychological loss, leading to a significant increase in public awareness of environmental problems. This study provides valuable insights for mitigating air pollution and reinforcing public health in developing countries.

Abstract PARP1 is crucial in DNA damage repair, chromatin remodeling, and transcriptional regulation. The principle of synthetic lethality has effectively guided the application of PARP inhibitors in treating tumors carrying BRCA1/2 mutations. Meanwhile, PARP inhibitors have exhibited efficacy in BRCA-proficient patients, further highlighting the necessity for a deeper understanding of PARP1 function and its inhibition in cancer therapy. Here, we unveil PIN2/TRF1-interacting telomerase inhibitor 1 (PINX1) as an uncharacterized PARP1-interacting protein that synergizes with PARP inhibitors upon its depletion across various cancer cell lines. Loss of PINX1 compromises DNA damage repair capacity upon etoposide treatment. The vulnerability of PINX1-deficient cells to etoposide and PARP inhibitors could be effectively restored by introducing either a full-length or a mutant form of PINX1 lacking telomerase inhibitory activity. Mechanistically, PINX1 is recruited to DNA lesions through binding to the ZnF3-BRCT domain of PARP1, facilitating the downstream recruitment of the DNA repair factor XRCC1. In the absence of DNA damage, PINX1 constitutively binds to PARP1, promoting PARP1-chromatin association and transcription of specific DNA damage repair proteins, including XRCC1, and transcriptional regulators, including GLIS3. Collectively, our findings identify PINX1 as a multifaceted partner of PARP1, crucial for safeguarding cells against genotoxic stress and emerging as a potential candidate for targeted tumor therapy.

Abstract Objectives Acute ischemic stroke (AIS) is caused by cerebral ischemia due to thrombosis in the blood vessel. The purpose of this study is to identify key genes related to metabolism to aid in the mechanism research and management of AIS. Materials and Methods Gene expression data were downloaded from the Gene Expression Omnibus database. Weighted gene co‐expression network analysis, Gene Ontology and kyoto encyclopedia of genes and genomes analysis were used to identify metabolism‐related genes that may be involved in the regulation of AIS. A protein protein interaction network was mapped using Cytoscape based on the STRING database. Subsequently, hub metabolism‐related genes were identified based on Cytoscape‐CytoNCA and Cytoscape‐MCODE plug‐ins. Least absolute shrinkage and selection operator algorithm and differential expression analysis. In addition, drug prediction, molecular docking, ceRNA network construction, and correlation analysis with immune cell infiltration were performed to explore their potential molecular mechanisms of action in AIS. Finally, the expression of hub gene was verified by real‐time PCR. Results Metabolism‐related genes FBL, HEATR1, HSPA8, MTMR4, NDUFC1, NDUFS8 and SNU13 were identified. The AUC values of FBL, HEATR1, HSPA8, MTMR4, NDUFS8 and SNU13 were all greater than 0.8, suggesting that they had good diagnostic accuracy. Correlation analysis found that their expression levels were also related to the infiltration levels of multiple immune cells, such as Activated.CD8.T.cell and Activated.dendritic.cell. It was found that only HSPA8 was successfully matched to drugs with literature support, and these drugs were acetaminophen, bupivacaine, dexamethasone, gentamicin, tretinoin and cisplatin. Moreover, it was also identified that the ENSG000000218510‐hsa‐miR‐330‐3p‐HEATR1 axis may be involved in regulating AIS. Conclusions The identification of FBL, HEATR1, HSPA8, MTMR4, NDUFC1, NDUFS8 and SNU13 provides a new research direction for exploring the molecular mechanisms of AIS, which can help in clinical management and diagnosis.

Abstract To examine the potential correlation between chemotherapy and the risk of individual of second primary endometrial cancer (SEC) in patients with rectal cancer (RC) and assess survival outcomes. The study employed the Surveillance, Epidemiology, and End Results database (SEER) as the primary data source, it encompasses a substantial cohort of patients diagnosed with RC between 1975 and 2018. This study involved a total of 30,847 individuals diagnosed with RC, of whom 168 individuals (5.45‰) experienced SEC. Among them, 107 patients (3.47‰) received chemotherapy treatment, while 61 patients (1.98‰) did not receive chemotherapy. The analysis of the overall occurrence of SEC revealed a significant association between SEC and chemotherapy treatment. Univariate and multivariate analyses confirmed a significant association between chemotherapy treatment and an increased risk of developing SEC in RC patients. Upon implementation of a dynamic analysis on the variables of relative risk and standardized incidence ratios, the results revealed that the likelihood of SEC escalated in tandem with advancing age. The examination of patients who developed SEC after receiving and not receiving chemotherapy revealed no substantial disparities in the 10-year overall survival (OS) and (cancer-specific survival) CSS rates. The results were the same after propensity score matching. Nevertheless, a notable discrepancy emerged when comparing the OS and CSS rates at 10 years between patients afflicted with SEC subsequent to chemotherapy and those afflicted with primary endometrial cancer, and the result was the same situation in the no-chemotherapy group. The use of chemotherapy in RC patients has been associated with an increased probability of developing specific SEC. Therefore, it is imperative to prioritize efforts aimed at reducing chemotherapy-related SEC occurrences and improving the prognosis of affected individuals.

Abstract Ubiquitin-like with PHD and RING finger domains 1 (UHRF1) is an epigenetic regulator that plays critical roles in tumours. However, the DNA methylation alteration patterns driven by UHRF1 and the related differentially expressed tumour-related genes remain unclear. In this study, a UHRF1-shRNA MCF-7 cell line was constructed, and whole-genome bisulfite sequencing and RNA sequencing were performed. The DNA methylation alteration landscape was elucidated, and DNA methylation-altered regions (DMRs) were found to be distributed in both gene bodies and adjacent regions. The DMRs were annotated and categorized into 488 hypermethylated/1696 hypomethylated promoters and 1149 hypermethylated/5501 hypomethylated gene bodies. Through an integrated analysis with the RNA sequencing data, 217 methylation-regulated upregulated genes and 288 downregulated genes were identified, and these genes were primarily enriched in nervous system development and cancer signalling pathways. Further analysis revealed 21 downregulated oncogenes and 15 upregulated TSGs. We also showed that UHRF1 silencing inhibited cell proliferation and migration and suppressed tumour growth in vivo. Our study suggested that UHRF1 and the oncogenes or TSGs it regulates might serve as biomarkers and targets for breast cancer treatment.

Abstract It has not yet been proven whether sepsis affects the tissue around the anal canal. To address this issue, we established three-dimensional models for various types of anorectal abscesses and utilize 3D reconstruction of Magnetic Resonance Imaging scans to assess the extent of muscle damage caused by anorectal abscesses. Patients diagnosed with anorectal abscess, selected from January 2019 to January 2022 underwent pre- and post-operative scanning of pelvic floor and perianal tissues. The aforementioned structures were segmented for the reconstruction of a three-dimensional visual model and measurement of volumes for the abscess as well as the internal and external sphincters and levator ani muscle. The study included a total of 42 patients. Three-dimensional visualization models were created for different types of anorectal abscesses, including perianal, intersphincteric, ischiorectal, and supralevator abscesses. No statistically significant differences were observed in the volume of the internal sphincter, external sphincter, and levator ani muscle between pre- and post-operative patients. The 3D model of anorectal abscess, reconstructed from MRI data, offers a precise and direct visualization of the anatomical structures associated with various types of anorectal abscesses. The infection did not result in any damage to the internal and external anal sphincter and levator ani muscle.

Abstract Background Extensive research has been conducted on embryonic developmental disorders linked to Polycystic Ovary Syndrome (PCOS), a pathological condition that affects 5−10% of women and is characterized by irregularities in the menstrual cycle and infertility. By employing RNA sequencing (RNA-seq), we performed an in-depth investigation of PCOS-related changes in gene expression patterns at the mouse blastocyst stage. Methods The zygotes of female B6D2 mice were obtained and then differentiated into blastocysts in K + Simplex Optimised Medium (KSOM) cultures containing exo-NC (negative control for exosomes) or exo-LIPE-AS1 (a novel exosomal marker of PCOS). Subsequently, blastocysts were collected for RNA-seq. The bioinformatics was performed to analyze and compare the differences of gene expression profile between blastocysts of control and PCOS group. Results There were 1150 differentially expressed genes (DEGs) between the two groups of mouse blastocysts; 243 genes were upregulated and 907 downregulated in the blastocysts of the exo-LIPE-AS1 group compared to those of the exo-NC group. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the genes involved in amino acid synthesis and glutathione metabolic pathways were down-regulated in exo-LIPE-AS1 group. Conclusion This study has revealed that blastocyst developmental retardation may be associated with the downregulation of amino acid synthesis and glutathione metabolism, which may affect energy metabolism, biosynthesis, cellular osmotic pressure, antioxidant synthesis, ROS clearance or mitochondrial function, and ultimately cause blastocyst cell development abnormalities. Our research offers encouraging data on the mechanisms underlying aberrant embryonic development in patients with PCOS as well as potential treatment strategies.

Abstract Backgrounds To our knowledge, there is no available nationwide data on omicron symptom patterns in China mainland. We aim to determine the acute and long COVID-19 symptoms in the omicron-dominant period and to evaluate its association with risk factors. Methods We designed a cross-sectional nationwide study and data about self-reported symptoms were collected by an online platform named Wenjuanxing. Eligible participants were aged 25–65 years and were symptomatic. In this study, the ratios of the number of people of different ages and genders were weighted by the data from the Seventh National Census (2020 years), and validated by a published nationwide representative study through comparing smoking rates. Descriptive indicators were calculated for demographic characteristics, diagnosis ways, and duration time, acute symptoms, hospitalization, severity and long COVID-19 symptoms. And, the associations between risk factors and acute and long COVID-19 symptoms were analyzed by multivariable logistic regression models. Results A total of 32,528 individuals diagnosed as COVID-19 infection from October 1, 2022 to February 21, 2023 were included. The first three acute symptoms of COVID-19 infection were fever (69.90%), headache (62.63%), and sore throat (54.29%), respectively. The hospitalization rate within 7 days was 3.07% and symptoms disappearance rate within 21 days was 68.84%, respectively. Among 3983 COVID-19 patients with 3 months or more time difference between first infection and participation into the study, the long COVID-19 rate was 19.68% and the primary symptoms were muscle weakness (19.39%), headache (17.98%) and smell/taste disorder (15.18%). Age groups, smoking, marriage status and vaccination were risk factors for numbers of acute phase symptoms and long COVID-19 symptoms. Lastly, female and current smokers also showed more numbers of symptoms during acute infection period. Conclusions In Chinese mainland, our respondent indicated that current smokers and women were associated with acute COVID-19 symptoms, which should be treated with caution due to the lack of representative.

Abstract Percutaneous renal biopsy is commonly used for kidney cancer diagnosis. However, the biopsy procedure remains challenging in sampling accuracy. Here we introduce a forward-viewing optical coherence tomography probe for differentiating tumor and normal tissues, aiming at precise biopsy guidance. Totally, ten human kidney samples, nine of which had malignant renal carcinoma and one had benign oncocytoma, were used for system evaluation. Based on their distinct imaging features, carcinoma could be efficiently distinguished from normal renal tissues. Additionally, oncocytoma could be differentiated from carcinoma. We developed convolutional neural networks for tissue recognition. Compared to the conventional attenuation coefficient method, convolutional neural network models provided more accurate carcinoma predictions. These models reached a tissue recognition accuracy of 99.1% on a hold-out set of four kidney samples. Furthermore, they could efficiently distinguish oncocytoma from carcinoma. In conclusion, our convolutional neural network-aided endoscopic imaging platform could enhance carcinoma diagnosis during percutaneous renal biopsy procedures.

Abstract Large language models have achieved outstanding performance on various downstream tasks with their advanced understanding of natural language and zero-shot capability. However, they struggle with knowledge constraints, particularly in tasks requiring complex reasoning or extended logical sequences. These limitations can affect their performance in question answering by leading to inaccuracies and hallucinations. This paper proposes a novel framework called KnowledgeNavigator that leverages large language models on knowledge graphs to achieve accurate and interpretable multi-hop reasoning. Especially with an analysis-retrieval-reasoning process, KnowledgeNavigator searches the optimal path iteratively to retrieve external knowledge and guide the reasoning to reliable answers. KnowledgeNavigator treats knowledge graphs and large language models as flexible components that can be switched between different tasks without additional costs. Experiments on three benchmarks demonstrate that KnowledgeNavigator significantly improves the performance of large language models in question answering and outperforms all large language models-based baselines.

In the field of labor protection, the real-time monitoring of workers’ physical health status has received a lot of attention. Because breathing contains a lot of physiological information, the development of wearable devices with sensing functions for monitoring the wearer’s respiratory status has become a research hotspot. Traditional commercial respiratory monitoring devices are expensive, bulky, and not easy to be carried, limiting their use in front-line production sites, such as high dust mass concentration mines’ operating environments. In view of this situation, based on the piezoelectric properties of polyvinylidene fluoride (PVDF), a flexible PVDF nanofiber membrane with sensing properties was prepared using electrospinning technology. The high permeability carbon fiber felt and PVDF nanofiber membrane were designed as a sandwich structure. The sensing module was embedded in the mask. The sensor module converted the mechanical energy generated by the respiratory airflow into electrical energy. Through the collection and analysis of electrical signal data, the real-time monitoring of respiratory intensity and respiratory frequency was completed. The results show that the piezoelectric signals generated by the mask embedded with the sensing module are significantly different under different breathing states. Under the three breathing states of low intensity (15 L/min), medium intensity (50 L/min) and high intensity (85 L/min), the output piezoelectric voltage peaks are 300, 700 and 1 100 mV, respectively, and the frequency of voltage peaks is 18, 16 and 14 times/min, respectively. Therefore, based on the analysis of the peak voltage and its frequency of the piezoelectric signal, the real-time monitoring of respiratory parameters such as the wearer's respiratory intensity and respiratory frequency can be realized. In addition, the piezoelectric properties of PVDF nanofiber membranes were determined to be related to the content of β-phase crystals by XRD, FT-IR, TG and other analysis methods, which provided a basis for further improving the piezoelectric properties of PVDF nanofiber membranes. The developed mask with sensing function can be used for the real-time respiratory monitoring of mine workers’ working conditions, and the feedback to managers when workers’ working conditions are abnormal to facilitate some timely treatment measures.

Abstract Studying the spatial and temporal changes of grassland soil organic carbon (SOC) is helpful in promote the management of regional ecosystem carbon sinks. Grazing is one of the main ways of rational utilization of grassland. Different grazing intensities will affect the change of SOC density. Under different grazing intensity and management measures in Zhangye grassland, this study uses the parameter localized CENTURY model to simulate the temporal and spatial variations of SOC density from 1970 to 2022. The results showed that long-term light grazing reduced the average SOC by 195.114 g·m−2 and 1.91%. Moderate and severe grazing, respectively, for a long time made the total SOC density loss of 5.21% and 17.69%. In a short period, mild and moderate grazing reduced total SOC first and then increased it. Under light grazing, total SOC density appeared higher relative changes in the southeast, and lower in the northwest and central. There was no significant difference in the relative changes of total SOC between steppe and desert grasslands under light grazing. The decrease range of steppe was gradually greater than that in desert grassland. Since different management measures were implemented in some sampling sites in 2017, we divided the study period into two periods, 1970–2016 and 2017–2022. The implementation of degraded grassland improvement, fallow grazing, and rotational grazing would increase the total SOC density and mild SOC density, rotational grazing > degraded grassland improvement > rest grazing. Rotational grazing and the improvement of degraded grassland increased the density of active and inert SOC, while resting grazing decreased the density of SOC.

Abstract Purpose To evaluate the impact of two different parameters (body position and distension medium) on the rectal sensory test in patients with functional constipation and provide data support for the development of standardized operating procedures in clinical practice. Methods Based on a single-center process of the rectal sensory test, 39 patients with functional constipation were recruited for rectal sensory test under different body positions and distension mediums. Results Among the items of the Constipation Scoring System, the score of frequency of bowel movements showed a negative correlation with the first constant sensation volume (r = -0.323, P = 0.045). Conversely, the score of painful evacuation effort showed a positive correlation with the desire to defecate volume (r = 0.343, P = 0.033). There was a statistically significant difference in the first constant sensation volume (when the distension medium was gas) measured in different body positions (left lateral position, sitting position, squatting position), and the data measured in the squatting position were significantly higher than those in left lateral position (P

Abstract Genome-wide association studies (GWAS) for biomarkers important for clinical phenotypes can lead to clinically relevant discoveries. Conventional GWAS for quantitative traits are based on simplified regression models modeling the conditional mean of a phenotype as a linear function of genotype. We draw attention here to an alternative, lesser known approach, namely quantile regression that naturally extends linear regression to the analysis of the entire conditional distribution of a phenotype of interest. Quantile regression can be applied efficiently at biobank scale, while having some unique advantages such as (1) identifying variants with heterogeneous effects across quantiles of the phenotype distribution; (2) accommodating a wide range of phenotype distributions including non-normal distributions, with invariance of results to trait transformations; and (3) providing more detailed information about genotype-phenotype associations even for those associations identified by conventional GWAS. We show in simulations that quantile regression is powerful across both homogeneous and various heterogeneous models. Applications to 39 quantitative traits in the UK Biobank demonstrate that quantile regression can be a helpful complement to linear regression in GWAS and can identify variants with larger effects on high-risk subgroups of individuals but with lower or no contribution overall.

Abstract Catalytic coal gasification is a promising technology in the field of clean coal utilization. A comprehensive understanding of mechanisms, reaction kinetic, and reactor model is crucial. This article summarizes and analyzes the catalytic mechanisms of key reactions, such as C–O2, C–CO2, C–H2O, and CO–H2. It also compares various kinetic models, including shrinking core model, random pore model, volume model and their respective modifications. Additionally, the article delves into mathematical modellings of catalytic coal gasification, encompassing molecular models or density functional theory, empirical model, computational fluid dynamics, Aspen modeling, and artificial neural network. The aim is to provide a roadmap for the development and scale up of reactors used in catalytic coal gasification.

Bonsai is a kind of classical art in China and Japan. The traditional method of bonsai shaping of miniature trees is technical and usually requires experienced horticulturists to successfully carry out the process. In order to let ordinary people feel the fun of bonsai shaping, this paper proposes a fast bonsai shaping method, i.e., by use of a plastic guiding mold with customized shape, which is processed by fused deposition 3D printing technology. The tree seedling is bundled onto the mold, and the shape of the mold guides the growth of the tree seedling, thus achieving the purpose of bonsai shaping. In order to further improve the bending properties of the bonsai guiding mold, this paper investigated the main 3D printing parameters of ABS filament. The results showed that with the decrease of printing speed, the increase of extrusion temperature, and the increase of hot bed temperature, the bending strength and elastic modulus of ABS specimens increased, and the bending properties was enhanced; the optimal printing speed was 50 mm/s, the extrusion temperature was 230 °C, and the hot bed temperature was 80 °C. The mechanical properties of the bonsai guiding mold manufactured based on the optimal process parameters were better, the print quality was higher, and it had high practical value.

Abstract Polymer materials suffer mechano-oxidative deterioration or degradation in the presence of molecular oxygen and mechanical forces. In contrast, aerobic biological activities combined with mechanical stimulus promote tissue regeneration and repair in various organs. A synthetic approach in which molecular oxygen and mechanical energy synergistically initiate polymerization will afford similar robustness in polymeric materials. Herein, aerobic mechanochemical reversible-deactivation radical polymerization was developed by the design of an organic mechano-labile initiator which converts oxygen into activators in response to ball milling, enabling the reaction to proceed in the air with low-energy input, operative simplicity, and the avoidance of potentially harmful organic solvents. In addition, this approach not only complements the existing methods to access well-defined polymers but also has been successfully employed for the controlled polymerization of (meth)acrylates, styrenic monomers and solid acrylamides as well as the synthesis of polymer/perovskite hybrids without solvent at room temperature which are inaccessible by other means.

Abstract Background Minimally invasive glaucoma surgery (MIGS) has experienced a surge in popularity in recent years. Glaucoma micro-stents serve as the foundation for these minimally invasive procedures. Nevertheless, the utilization of these stents still presents certain short-term and long-term complications. This study aims to elucidate the creation of a novel drainage stent implant featuring a diverging channel, produced through microfluidic template processing technology. Additionally, an analysis of the mechanical properties, biocompatibility, and feasibility of implantation is conducted. Results The stress concentration value of the proposed stent is significantly lower, approximately two to three times smaller, compared to the currently available commercial XEN gel stent. This indicates a stronger resistance to bending in theory. Theoretical calculations further reveal that the initial drainage efficiency of the gradient diverging drainage stent is approximately 5.76 times higher than that of XEN stents. Notably, in vivo experiments conducted at the third month demonstrate a favorable biocompatibility profile without any observed cytotoxicity. Additionally, the drainage stent exhibits excellent material stability in an in vitro simulation environment. Conclusions In summary, the diverging drainage stent presents a novel approach to the cost-effective and efficient preparation process of minimally invasive glaucoma surgery (MIGS) devices, offering additional filtering treatment options for glaucoma.