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Abstract Understanding biological activities in cells or deep tissues requires high-speed three-dimensional (3D) imaging. Substantial progress has been made with the emergence of 3D random-access microscopy. However, current solutions for fast 3D random-access imaging remain complex and costly. Herein we propose a simple, cost-effective, and fast 3D random-access confocal microscopy with remote focusing system. Our system shows isotropic response times across the x, y, and z axes, with a 34-fold improvement in axial response time over traditional piezo stages. We demonstrate its volumetric imaging performance with fluorescent particles and live cells. Furthermore, we validate the 3D random-access imaging capability of this system by continuously monitoring the signals in three different planes, showing a refresh rate of 500 Hz on two different positions in 3D. The simplicity, versatility, and affordability of our system promise widespread applications in research and industry.

Abstract Background It is very important to provide the correct nursing care for patients with intracerebral hemorrhage (ICH), but the level of critical care needs in patients with intracerebral hemorrhage is not clear. The purpose of this study is to establish a risk model based on the epidemiological and clinical characteristics of ICH patients, to help identify the critical care needs of ICH patients. Methods The clinical data of ICH patients from January 2018 to September 2023 were analyzed retrospectively. The full cohort was used to derive the clinical prediction model and the model was internally validated with bootstrapping. Discrimination and calibration were assessed using the area under curve (AUC) and the Hosmer-Lemeshow tests, respectively. Results 611 patients with ICH were included for model development. 61.21% (374/611) ICH patients had received critical care interventions. The influencing factors included in the model were Glasgow Coma Scale (GCS) score, intraventricular hemorrhage, past blood pressure control, systolic blood pressure on admission and bleeding volume. The model’s goodness-of-fit was evaluated, which yielded a high area under the curve (AUC) value of 0.943, indicating a good fit. For the purpose of model validation, a cohort of 260 patients with ICH was utilized. The model demonstrated a Youden’s index of 0.750, with a sensitivity of 90.56% and a specificity of 78.22%. Conclusion GCS, systolic blood pressure, intraventricular hemorrhage, bleeding volume and past blood pressure control are the main factors affecting the critical care needs of patients with ICH. This study has deduced a clinical predictive model with good discrimination and calibration to provide scoring criteria for clinical health care providers to accurately evaluate and identify the critical care needs of ICH patients, to improve the rational integration and allocation of medical resources.

Abstract The pandemic crisis outbreak has impacted the hospitality industry tremendously. This study investigated the effect of job insecurity on service performance and examined the mediating role of cognitive appraisal and the moderating effect of uncertainty tolerance from the perspectives of cognitive appraisal theory of stress. The study collected a questionnaire from 316 hotel employees at three time points, with a one-month interval between the two time points. The SPSS PROCESS macro and MPLUS are used to test the research hypotheses. The results highlighted that the mediating role of challenge-hindrance appraisal, affirming that job insecurity positively impacts service performance via increasing challenge appraisal, and job insecurity negatively impacts service performance via increasing hindrance appraisal. Furthermore, the results show that uncertainty tolerance moderates the relationship between job insecurity and cognitive appraisal and also moderated the indirect effect of job insecurity on service performance through cognitive appraisal. The research results provide implications for human resource management in the hospitality industry.

[Introduction] As an important carrier of China's industrialization and urbanization, industrial parks not only provide a large amount of infrastructure and public services, but also become the main source of carbon emission in China and an important entry and focus point for achieving China's goals of carbon peaking and carbon neutrality. The paper proposes a theoretical research framework for analyzing the transfer process of carbon emission in industrial parks and optimizing the decision-making process of the "dual carbon" path, in order to achieve the refined management of carbon emission in industrial parks. [Method] Firstly, we analyzed the carbon emission characteristics of energy, industry, construction, transportation, and infrastructure in industrial parks, and established a carbon emission accounting model for industrial parks based on inventory analysis method. Secondly, considering the impact of factors such as gross industrial output value, industrial structure, energy structure, and energy consumption on carbon emission, we established a decomposition model of factors influencing carbon emission based on the STIRPAT method. Finally, we analyzed the mechanism and impact path of digital technology empowering green and low-carbon transformation, and proposed the optimization plan for decision-making of the "dual carbon" path. [Result] Taking Ganzhou economic and technological development zone in Jiangxi Province as the research object, we calculate the carbon emission and carbon emission intensity from 2020 to 2022, identify the main factors influencing the increase of carbon emission, and plan the "dual carbon" transformation path from four aspects: industrial structure, energy structure, policy system, and platform construction. [Conclusion] Research suggests that the proposed model can fully explore the information contained in statistical data of industrial parks and is scientific and effective, providing theoretical support for the decision-making of "dual carbon" transformation path and the construction of industrial internet platform for digital carbon management of industrial parks.

Abstract Among the many far-reaching consequences of the potential existence of a magnetic monopole, it induces a topological zero mode in the Dirac equation, which was derived by Jackiw and Rebbi 48 years ago and has been elusive ever since. Here, we show that the monopole and multi-monopole solutions can be constructed in the band theory by gapping the three-dimensional Dirac points in hedgehog mass configurations. We then experimentally demonstrate such a monopole bound state in an optimized Dirac acoustic crystal structurally modulated in full solid angles. The monopole mode exhibits the optimal scaling behavior — whose modal spacing is inversely proportional to the cubic root of the modal volume. This work completes the kink-vortex-monopole zero-mode trilogy and paves the way for exploring higher-dimensional bulk-topological-defect correspondence.

Abstract Background Bread wheat (Triticum aestivum L.) endosperm contains starch and proteins, which determine the final yield, quality, and nutritional value of wheat grain. The preferentially expressed endosperm genes can precisely provide targets in the endosperm for improving wheat grain quality and nutrition using modern bioengineering technologies. However, the genes specifically expressed in developing endosperms remain largely unknown. Results In this study, 315 preferentially expressed endosperm genes (PEEGs) in the spring wheat landrace, Chinese Spring, were screened using data obtained from an open bioinformatics database, which reveals a unique grain reserve deposition process and special signal transduction in a developing wheat endosperm. Furthermore, transcription and accumulation of storage proteins in the wheat cultivar, XC26 were evaluated. The results revealed that 315 PEEG plays a critical role in storage protein fragment deposition and is a potential candidate for modifying grain quality and nutrition. Conclusion These results provide new insights into endosperm development and candidate genes and promoters for improving wheat grain quality through genetic engineering and plant breeding techniques.

Abstract Computational technologies based on coupled oscillators are of great interest for energy efficient computing. A key to developing such technologies is the tunable control of the interaction among oscillators which today is accomplished by additional electronic components. Here we show that the synchronization of closely spaced vanadium dioxide (VO2) oscillators can be controlled via a simple thermal triggering element that itself is formed from VO2. The net energy consumed by the oscillators is lower during thermal coupling compared with the situation where they are oscillating independently. As the size of the oscillator shrinks from 6 μm to 200 nm both the energy efficiency and the oscillator frequency increases. Based on such oscillators with active tuning, we demonstrate AND, NAND, and NOR logic gates and various firing patterns that mimic the behavior of spiking neurons. Our findings demonstrate an innovative approach towards computational techniques based on networks of thermally coupled oscillators.

Abstract The manipulation of spin textures by spin currents is of fundamental and technological interest. A particularly interesting system is the 2D van der Waals ferromagnet Fe3GeTe2, in which Néel-type skyrmions have recently been observed. The origin of these chiral spin textures is of considerable interest. Recently, it was proposed that these derive from defects in the structure that lower the symmetry and allow for a bulk vector Dzyaloshinsky-Moriya interaction. Here, we demonstrate current-induced domain wall motion in Fe3GeTe2 flakes, in which the maximum domain wall velocity is an order of magnitude higher than those reported in previous studies. In heterostructures with Pt or W layers on top of the Fe3GeTe2 flakes, domain walls can be moved via a combination of spin transfer and spin-orbit torques. The competition between these torques leads to a change in the direction of domain wall motion with increasing magnitude of the injected current.

Background: Glioblastoma (GBM) poses a significant medical challenge due to its aggressive nature and poor prognosis. Mitochondrial unfolded protein response (UPRmt) and the heat shock factor 1 (HSF1) pathway play crucial roles in GBM pathogenesis. Post-translational modifications, such as SUMOylation, regulate the mechanism of action of HSF1 and may influence the progression of GBM. Understanding the interplay between SUMOylation-modified HSF1 and GBM pathophysiology is essential for developing targeted therapies. Methods: We conducted a comprehensive investigation using cellular, molecular, and in vivo techniques. Cell culture experiments involved establishing stable cell lines, protein extraction, Western blotting, co-immunoprecipitation, and immunofluorescence analysis. Mass spectrometry was utilized for protein interaction studies. Computational modeling techniques were employed for protein structure analysis. Plasmid construction and lentiviral transfection facilitated the manipulation of HSF1 SUMOylation. In vivo studies employed xenograft models for tumor growth assessment. Results: Our research findings indicate that HSF1 primarily undergoes SUMOylation at the lysine residue K298, enhancing its nuclear translocation, stability, and downstream heat shock protein expression, while having no effect on its trimer conformation. SUMOylated HSF1 promoted the UPRmt pathway, leading to increased GBM cell proliferation, migration, invasion, and reduced apoptosis. In vivo studies have confirmed that SUMOylation of HSF1 enhances its oncogenic effect in promoting tumor growth in GBM xenograft models. Conclusion: This study elucidates the significance of SUMOylation modification of HSF1 in driving GBM progression. Targeting SUMOylated HSF1 may offer a novel therapeutic approach for GBM treatment. Further investigation into the specific molecular mechanisms influenced by SUMOylated HSF1 is warranted for the development of effective targeted therapies to improve outcomes for GBM patients.

Prostate cancer (PCa) currently ranks second in male tumor mortality. Targeting immune checkpoint in tumor as immunotherapy is a new direction for tumor treatment. However, targeting PD-1/PD-L1 and CTLA4 to treat PCa has poor immunotherapeutic efficacy because PCa is known as a cold tumor. Understanding the mechanism of immunosuppression in PCa can promote the use of immunotherapy to treat PCa. ELAVL1 is highly expressed in many tumors, participates in almost all tumor biological activities and is an oncogene. ELAVL1 is also involved in the development and differentiation of T and B lymphocytes. However, the relationship between ELAVL1 and tumor immunity has not yet been reported. In recent years, ELAVL1 has been shown to regulate downstream targets in an m6A -dependent manner. PD-L1 has been shown to have m6A sites in multiple tumors that are regulated by m6A. In this study, ELAVL1 was highly expressed in PCa, and PCa with high ELAVL1 expression is immunosuppressive. Knocking down ELAVL1 reduced PD-L1 expression in PCa. Moreover, PD-L1 was shown to have an m6A site, and its m6A level was upregulated in PCa. ELAVL1 interacts with PD-L1 mRNA and promotes PD-L1 RNA stability via m6A, ultimately inhibiting the infiltration of CD4-positive T cells. In addition, androgen receptor (AR) was shown to be regulated with ELAVL1, and knocking down AR could also affect the expression of PD-L1. Therefore, ELAVL1 can directly or indirectly regulate the expression of PD-L1, thereby affecting the infiltration of CD4-positive T cells in PCa and ultimately leading to immune suppression.

ABSTRACT: Recently, poultry industry has been seeking antibiotic residue-free poultry products and safe nutritious feed additives. Whether rosemary ultrafine powder (RUP) affects productive performance by regulating the intestinal microbiome of aged layers remains unclear. Here, we investigated the effects of dietary RUP supplementation on the production performance, egg quality, antioxidant capacity, intestinal microbial structure, and metabolome of aged hens. The results indicate that RUP had no significant effect on production performance but significantly enhanced Thick albumen height, Haugh unit, yolk color (P < 0.05), daily feed intake, and qualified egg rate. Serum content of non-esterified fatty acids, catalase, and glutathione peroxidase increased significantly (P < 0.05). Furthermore, the liver total protein content was significantly increased (P < 0.05). 16S rRNA sequence analysis revealed that RUP significantly impacted both α- and β-diversity of the caecum microbiota. Linear discriminant analysis of effect size and random forest identified Bacteroides, Muribaculum, Butyricimonas, Odoribacter, and Prevotella as biomarkers in groups A and B. In comparing groups A and C, Barnesiella, Turicibacter, and Acholeplasma were critical bacteria, while comparing groups A and D highlighted Barnesiella and Candidatus Saccharimonas as differential bacteria. FAPROTAX analysis of the caecum microbiota revealed that the functional genes associated with harmful substance biodegradation were significantly increased in the RUP-fed group. Based on Spearman correlation analysis, alterations in microbial genera were associated with divergent metabolites. In summary, dietary RUP can improve egg quality and antioxidant capacity and regulate the intestinal microbiome and metabolome in aged breeders. Therefore, RUP can potentially be used as a feed additive to extend breeder service life at an appropriate level of 1.0 g/kg.

Lexicon Enhanced Bidirectional Encoder Representations from Transformers (LEBERT) has achieved great success in Chinese Named Entity Recognition (NER). LEBERT performs lexical enhancement with a Lexicon Adapter layer, which facilitates deep lexicon knowledge fusion at the lower layers of BERT. However, this method is likely to introduce noise words and does not consider the possible conflicts between words when fusing lexicon information. To address this issue, we advocate for a novel lexical enhancement method, Sequential Lexicon Enhanced BERT (SLEBERT) for the Chinese NER, which builds sequential lexicon to reduce noise words and resolve the problem of lexical conflict. Compared with LEBERT, it leverages the position encoding of sequential lexicon and adaptive attention mechanism of sequential lexicon to enhance the lexicon feature. Experiments on the four available datasets identified that SLEBERT outperforms other lexical enhancement models in performance and efficiency.

Abstract Bacterial infection remains a major complication answering for the failures of various implantable medical devices. Tremendous extraordinary advances have been published in the design and synthesis of antimicrobial materials addressing this issue; however, the clinical translation has largely been blocked due to the challenge of balancing the efficacy and safety of these materials. Here, calcium's biochemical features, natural roles in pathogens and the immune systems, and advanced uses in infection medications are illuminated, showing calcium is a promising target for developing implantable devices with less infection tendency. The paper gives a historical overview of biomedical uses of calcium and summarizes calcium's merits in coordination, hydration, ionization, and stereochemistry for acting as a structural former or trigger in biological systems. It focuses on the involvement of calcium in pathogens’ integrity, motility, and metabolism maintenance, outlining the potential antimicrobial targets for calcium. It addresses calcium's uses in the immune systems that the authors can learn from for antimicrobial synthesis. Additionally, the advances in calcium's uses in infection medications are highlighted to sketch the future directions for developing implantable antimicrobial materials. In conclusion, calcium is at the nexus of antimicrobial defense, and future works on taking advantage of calcium in antimicrobial developments are promising in clinical translation.

Alkaline metal oxides have received significant attention recently due to their abundance, inherent conductivity, optical absorption, and thermal stability. Here, a straightforward co-precipitation method was employed to obtain both undoped BaO and Mo-doped BaO nanoparticles. Various techniques were used to characterize the synthesized nanoparticles’ structural, Raman spectral, optical, thermal, and electrical properties. X-ray diffraction (XRD) results revealed that Mo was successfully doped into tetragonal nanocrystalline BaO. The W-H plot showed that as Mo doping increases from 2 % to 6 %, the crystallite size grows while the lattice structure remains well-ordered with even strain distribution. Scanning electron microscopy (SEM) was used to examine its surface features. The purity and crystalline character of the samples were further confirmed via Raman spectroscopy, which shows that the peak intensity of the spectra increases with the increase of particle size owing to the rise in the force constant. UV spectroscopy was used to observe the energy band gap, which is found to decrease from 4.2 eV to 3.8 eV, and then it drops to 3.4 eV as the Mo content increases. This is reasonable because of the size-dependent attraction between metallic ions and conduction electrons. PL spectra concluded that Mo doping leads to the enhancement of the optical characteristics of BaO. Adding Mo to BaO also modifies the material’s thermal properties, potentially affecting its suitability for applications that require thermal durability. This finding exhibits that even slight doping of Mo4+ into BaO can significantly impact their structural, thermal, optical, and electrical characteristics. It enriches the existing body of knowledge of BaO nanoparticles and lays the foundation for its future research.

The McMurdo Dry Valleys (MDVs) of Antarctica are a mosaic of extreme habitats which are dominated by microbial life. The MDVs include glacial melt holes, streams, lakes, and soils, which are interconnected through the transfer of energy and flux of inorganic and organic material via wind and hydrology. For the first time, we provide new data on the viral community structure and function in the MDVs through metagenomics of the planktonic and benthic mat communities of Lakes Bonney and Fryxell. Viral taxonomic diversity was compared across lakes and ecological function was investigated by characterizing auxiliary metabolic genes (AMGs) and predicting viral hosts. Our data suggest that viral communities differed between the lakes and among sites: these differences were connected to microbial host communities. AMGs were associated with the potential augmentation of multiple biogeochemical processes in host, most notably with phosphorus acquisition, organic nitrogen acquisition, sulfur oxidation, and photosynthesis. Viral genome abundances containing AMGs differed between the lakes and microbial mats, indicating site specialization. Using procrustes analysis, we also identified significant coupling between viral and bacterial communities (p = 0.001). Finally, host predictions indicate viral host preference among the assembled viromes. Collectively, our data show that: (i) viruses are uniquely distributed through the McMurdo Dry Valley lakes, (ii) their AMGs can contribute to overcoming host nutrient limitation and, (iii) viral and bacterial MDV communities are tightly coupled.

1. Forest ecosystem is a basic component of terrestrial ecosystem that mitigates the impact of climate change through absorbing significant amount of carbon dioxide. Forest is crucial in maintaining ecological equilibrium, reducing greenhouse gas emission, and preserving biodiversity. Thus, standardised and precise methodologies for measuring forest carbon sequestration and assessing its potential are of paramount importance in evaluating the impacts of climate change.2. We presented the “forestat”, an approach for assessing forest carbon sequestration and its potential based on annual growth of biomass, considering site class and forest age conditions, wrapped in an R package, which is applicable to all forest types. By using a comprehensive system of forest stand models, “forestat” contributes to a refined comprehension of relationships between forest biomass and carbon sequestration and offers an evaluation of the carbon sequestration potential in forest ecosystem, unifying the methods of carbon measurement and its potential estimation in both natural and plantation forests.3. Based on the two applications, this study (a) introduces and demonstrates the methods in R package “forestat”; (b) uses the 6th, 7th, 8th, and 9th National Forest Inventory data to investigate carbon sequestration and potential productivity of degraded forests in China; and (c) conducts suitability analysis for tree species in the Yellow River Basin.4. “forestat” provides a unified, efficient, and standardized analytical tool for forest carbon sequestration and its potential. This study also highlights the primary forest functionalities.

Benign prostatic hyperplasia (BPH), characterized by the non-malignant enlargement of the prostate, exhibits a pronounced association with inflammation resulting from androgen receptor (AR) deficiency. Ferroptosis, a cell death mechanism triggered by iron-dependent lipid peroxidation and closely linked to inflammation, has yet to be fully understood in the context of BPH. Using RNA sequencing, we observed a significant elevation of taurine-upregulated gene 1 (TUG1) long noncoding RNA (lncRNA) in BPH tissues compared to normal prostate tissue. High levels of TUG1 exhibited a discernible correlation with both prostate volume and the extent of inflammatory infiltration in BPH patients. The suppression of TUG1 not only led to a reduction in prostate size but also ameliorated AR-deficiency-induced prostatic hyperplasia. Mechanistically, a decrease in AR in prostate luminal cells prompted macrophage aggregation and the release of IL-1β, subsequently fostering the transcription of TUG1 via MYC. Induced TUG1, through competitive binding with miR-188-3p, facilitated the expression of GPX4, thereby diminishing intracellular ROS levels and impeding ferroptosis in prostate luminal cells. Notably, the ferroptosis inducer JKE-1674 alleviated inflammation-induced prostatic hyperplasia in vivo. Together, these findings suggest that AR deficiency crucially inhibits ferroptosis, promoting BPH via the TUG1/miR-188-3p/GPX4 signaling axis, and making ferroptosis induction a promising therapeutic strategy for BPH patients with AR deficiency.

This study investigated the effects of dietary chlorogenic acid (CGA) on the productive and reproductive performance, egg quality, antioxidant function, and intestinal microenvironment of laying hens. Thus, 162 healthy Hy-Line Brown breeding hens (63 weeks old) were randomly allocated to 3 groups, each receiving a basal diet plus supplementation: 0, 250, and 500 mg/kg CGA, respectively. Per the in vitro test, CGA had obvious inhibitory effects on Salmonella enteritis and avian pathogenic Escherichia coli and strong free radical scavenging ability. Per the breeder laying hen experiment, the CGA diets had no significant influence on egg production or reproductive performance (P < 0.05). Nevertheless, compared with the control diet, 250 mg/kg CGA significantly increased eggshell thickness, egg weight, yolk color, and Haugh unit (P < 0.05). Compared with the control diet and 500 mg/kg CGA, 250 mg/kg CGA significantly (P < 0.05) elevated antioxidant capacity by reducing serum malondialdehyde content, upregulating heme oxygenase-1, and downregulating heat shock proteins mRNA levels in the ileum. Compared with the control diet and 500 mg/kg CGA, 250 mg/kg CGA (P < 0.05) enhanced intestinal barrier function, shown by the upregulation of ileal Occludin and Mucin-2 mRNA levels; furthermore, 250 mg/kg CGA (P < 0.05) increased anti-apoptotic capacity by increasing B-cell leukemia/lymphoma 2 gene expression and downregulated Bcl2 Associated X mRNA levels in the liver and ileum of late breeder laying hens (P < 0.05). Lastly, 250 mg/kg CGA (P < 0.05) increased cecal g_CHKCI001 and short-chain fatty acid-producing bacteria g_Prevotellaceae UCG-001, positively related to gut health, and in the cecum, 500 mg/kg CGA significantly (P < 0.05) increased g_Shuttleworthia abundance, negatively related to gut health. Our findings suggest that dietary inclusion of 250 mg/kg CGA promotes egg quality, intestinal microbial composition, gut barrier integrity, and the antioxidant capacity of aged breeder laying hens.

This work firstly oxidizes single-phase high entropy alloy (HEA) to form FCC and BCC dual-phase structure, and also introduces multi-component nano-oxides on surface to prepare oxidized HEA (OHEA) reinforcements, followed by preparation of OHEA/Al composites by spark plasma sintering. The introduction of O element accelerates interdiffusion between OHEA and Al matrix. FCC phase inside OHEA evolves into soft phase, and BCC matrix phase evolves into hard phase, forming heterogeneous interface in OHEA/Al composites. During tensile process, cracks preferentially initiated in hard phase due to severe stress concentration, and the soft phase effectively retarded crack propagation. Compared with 2024Al matrix, yield strength, tensile strength, and elongation of OHEA/Al composites increased by 35.31%, 57.34%, and 63.33%, respectively, realizing excellent combination of strength and toughness. Grain refinement, thermal mismatch, Orowan, and load transfer strengthenings synergistically improve the performance. The proposed method provides a promising avenue to optimize the properties of composites by pre-oxidizing HEA particles to construct heterogeneous interfacial structure.

With the development and application of torpedo weapons and equipment in future wars, new requirements for digitization, intelligence, and agility have been put forward. The practical problems faced by torpedoes in the traditional text-based development mode, such as the separation of the overall system and subsystems, as well as that of the design process and production process, lead to untimely error detection, insufficient early verification, incomplete information transmission, inconsistent model data, incomplete verification scope, and unclear process traceability. In order to solve these problems, shorten the torpedo development cycle, and improve development efficiency and quality, advanced system engineering methods and new technologies were both utilized. Based on the practical application research on model-based system engineering(MBSE) in China and abroad, this paper proposed a digital development method for torpedo weapons and equipment based on MBSE. The method integrated the MBSE idea with torpedo technology characteristics and research and development processes, constructed cross-stage, cross-discipline, and cross-level MBSE technology system for the entire lifecycle of torpedoes, proposed a digital application framework and technical roadmap for MBSE torpedo, and refined the main key technologies that needed to be addressed in the digital development process of MBSE torpedoes. The method proposed in this paper provides a reference for the digital development practice and comprehensive digital transformation of torpedo weapons and equipment.

Abstract Objective Proliferative nodular formation represents a characteristic pathological feature of benign prostatic hyperplasia (BPH) and serves as the primary cause for prostate volume enlargement and consequent lower urinary tract symptoms (LUTS). Its specific mechanism is largely unknown, although several cellular processes have been reported to be involved in BPH initiation and development and highlighted the crucial role of epithelial cells in proliferative nodular formation. However, the technological limitations hinder the in vivo investigation of BPH patients. Methods The robust cell type decomposition (RCTD) method was employed to integrate spatial transcriptomics and single cell RNA sequencing profiles, enabling the elucidation of epithelial cell alterations during nodular formation. Immunofluorescent and immunohistochemical staining was performed for verification. Results The alterations of epithelial cells during the formation of nodules in BPH was observed, and a distinct subgroup of basal epithelial (BE) cells, referred to as BE5, was identified to play a crucial role in driving this progression through the hypoxia-induced epithelial-mesenchymal transition (EMT) signaling pathway. BE5 served as both the initiating cell during nodular formation and the transitional cell during the transformation from luminal epithelial (LE) to BE cells. A distinguishing characteristic of the BE5 cell subgroup in patients with BPH was its heightened hypoxia and upregulated expression of FOS. Histological verification results confirmed a significant association between c-Fos expression and key biological processes such as hypoxia and cell proliferation, as well as the close relationship between hypoxia and EMT in BPH tissues. Furthermore, a strong link between c-Fos expression and the progression of BPH was also been validated. Additionally, notable functional differences were observed in glandular and stromal nodules regarding BE5 cells, with BE5 in glandular nodules exhibiting enhanced capacities for EMT and cell proliferation characterized by club-like cell markers. Conclusions This study elucidated the comprehensive landscape of epithelial cells during in vivo nodular formation in patients, thereby offering novel insights into the initiation and progression of BPH.

In order to clarify the microflora structure in Cheddar cheese processing, MiSeq high-throughput sequencing technology was used to analyze the community structure of Cheddar cheese at three stages of processing (post-pasteurization, curdling, and ripening 0, 30, 60 and 90 d) in this study. The results showed that the community structure varies widely of cheddar cheese during processing. The highest microbial community diversity and abundance were found after pasteurization (Chao1 index and Shannon index mean values were 6.09 and 1415.78, respectively). The dominant microflora in the pasteurization stage at the genus level was Stenotrophomonas (21.04%). The community structure was relatively similar in the curd and ripening stages, Lactococcus were the dominant flora in both stages, with abundance averaging more than 85%. During the ripening period, the relative abundance of Lactococcus increased first and then decreased. The community structure in the pasteurized cheeses was different compared to the other groups, and there was less change in the community structure of the groups during the ripening period. This study provides a basis for clarifying the community structure of Cheddar cheese, and has a certain reference value for the expansion of Cheddar cheese microbiome information.

Objective The risk of gastric cancer can be predicted by gastroscopic manifestation recognition and the Kyoto Gastritis Score. This study aims to validate the applicability of AI approaches for recognizing gastroscopic manifestations according to the definition of Kyoto Gastritis Score, with the goal of improving early gastric cancer detection and reducing gastric cancer mortality.Methods In this retrospective study, 29013 gastric endoscopy images were collected and carefully annotated into five categories according to the Kyoto Gastritis Score, i.e. atrophy (A), diffuse redness (DR), enlarged folds (H), intestinal metaplasia (IM), and nodularity (N). As a multi-label recognition task, we propose a deep learning approach composed of five GAM-EfficientNet models, each performing a multiple classification to quantify gastroscopic manifestations, i.e. no presentation or the severity score 0–2. This approach was compared with endoscopists of varying years of experience in terms of accuracy, specificity, precision, recall, and F1 score.Results The approach demonstrated good performance in identifying the five manifestations of the Kyoto Gastritis Score, with an average accuracy, specificity, precision, recall, and F1 score of 78.70%, 91.92%, 80.23%, 78.70%, and 0.78, respectively. The average performance of five experienced endoscopists was 72.63%, 90.00%, 77.68%, 72.63%, and 0.73, while that of five less experienced endoscopists was 66.60%, 87.44%, 70.88%, 66.60%, and 0.66, respectively. The sample t-test indicates that the approach’s average accuracy, specificity, precision, recall, and F1 score for identifying the five manifestations were significantly higher than those of less experienced endoscopists, experienced endoscopists, and all endoscopists on average (p

AbstractThe study analyzed hourly extreme precipitation events in Chongqing and its six sub-regions from 2011 to 2021 during the warm season. Results showed uneven distribution of the 99.7th percentile hourly extreme precipitation threshold, with lower thresholds along the Yangtze River valley and higher thresholds in the Daba Mountains and Wuling Mountains. Both hourly extreme precipitation amount (HEPA) and intensity (HEPI) exhibited higher values in surrounding areas and lower values in the center, with the western, northeast, and southeastern regions experiencing the highest values. Spatial distribution of hourly extreme precipitation frequency varied, with higher frequencies in the northwestern and southern parts of Chongqing. Interannually, hourly extreme precipitation amount slightly increased, while intensity fluctuated. Monthly peak values for amount, frequency, and intensity occurred in July or August, and on a daily scale, the periods from 03:00 to 07:00 and 17:00 to 21: 00 exhibited higher values for amount and frequency, while the period from 11 :00 to 16:00 showed lower values. In summary, the study provided insights into the spatial and temporal patterns of hourly extreme precipitation events in Chongqing and its sub-regions during the warm season, highlighting variations in thresholds, distribution, and trends over the studied period.

BackgroundRhabdomyosarcoma of the bladder is an infrequent neoplastic condition characterized by a pronounced malignant situation with challenges in treatment due to the lack of standardized guidelines and large-scale of clinical studies. The patient in this case is tested TP53 mutation that may provide new diagnostic and therapeutic options.Case presentationHere, we reported a 34-year-old male who received bladder tumor resection, and diagnosed as bladder rhabdomyosarcoma with TP53 mutation after the pathology test. This patient underwent 6 rounds of chemotherapy. However, the pelvic tumor recurred 11 months after the first surgery. So, the patient accepted the pelvic tumor resection. Only 3 months after the surgical intervention, the patient underwent abdominal massive metastasis and ultimately succumbed to the illness six months following the second surgery. The course of the illness was 22 months.ConclusionBladder rhabdomyosarcoma is a disease with an extremely poor prognosis. Genetic testing holds significant value in the diagnosis and treatment. Perhaps targeted therapy against TP53 is potential valuable for such rare diseases.

Lycoris is a perennial bulbous flower belonging to the Amaryllidaceae family, which is commonly known as surprise lily, hurricane lily, or spider lily due to its distinctive flowering characteristics. They bloom from summer to early fall when the flower stalks emerge from the ground without foliage, giving rise to name like “surprise lilies” (Knox 2006). Among the species, Lycoris radiata stands as a representative with its spider-like appearance, featuring six tepals arranged radially around a central reproductive structure. The petals display a diverse array of colors, including red, yellow, white, pink, and multicolor variations across different species and cultivars (Ji and Meerow 2000). In addition, the strap-like or linear-shaped leaves of Lycoris also add ornamental value, emerging before or after flowering and providing visual interest during winter and spring when the plants are not in bloom. Therefore, its surprising blooms, abundant colors, and unique growth habits make it valuable for gardens and cut flowers. According to the latest published data, there are more than 30 species in the genus, predominantly native to East Asia (Zhang et al. 2022b), with ∼80% of them naturally distributed in China. So, Lycoris boasts a rich cultivation history in Chinese gardens. Furthermore, ongoing research focuses on breeding new Lycoris cultivars, with unique traits. For instance, L. longituba cultivar Yi Xian Chun Tao exhibits pink-purple flowers, distinguishing from white L. longituba (Zhang et al. 2022a), and L. straminea cultivar E Huang Xiao Ran stands out with a larger plant and flower size with vivid red stripes on the petals, surpassing the color intensity of L. straminea (Wang et al. 2023). These new cultivars contribute to horticultural diversity and hold higher economic value for landscape and cut flower application.

BackgroundThe gut microbiome plays a key role in the formation of livestock and poultry traits via serum metabolites, and empirical evidence has indicated these traits are sex-linked.MethodsWe examined 106 chickens (54 male chickens and 52 female chickens) and analyzed cecal content samples and serum samples by 16S rRNA gene sequencing and non-targeted metabolomics, respectively.ResultsThe cecal microbiome of female chickens was more stable and more complex than that of the male chickens. Lactobacillus and Family XIII UCG-001 were enriched in male chickens, while Eubacterium_nodatum_group, Blautia, unclassified_Anaerovoraceae, Romboutsia, Lachnoclostridium, and norank_Muribaculaceae were enriched in female chickens. Thirty-seven differential metabolites were identified in positive mode and 13 in negative mode, showing sex differences. Sphingomyelin metabolites possessed the strongest association with cecal microbes, while 11β-hydroxytestosterone showed a negative correlation with Blautia.ConclusionThese results support the role of sexual dimorphism of the cecal microbiome and metabolome and implicate specific gender factors associated with production performance in chickens.

Background Lysyl oxidase enzymes (LOXs), as extracellular matrix (ECM) protein regulators, play vital roles in tumor progression by remodeling the tumor microenvironment. However, their roles in glioblastoma (GBM) have not been fully elucidated. Methods The genetic alterations and prognostic value of LOXs were investigated via cBioPortal. The correlations between LOXs and biological functions/molecular tumor subtypes were explored in The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA). After Kaplan‒Meier and Cox survival analyses, a Loxl1-based nomogram and prognostic risk score model (PRSM) were constructed and evaluated by time-dependent receiver operating characteristic curves, calibration curves, and decision curve analyses. Tumor enrichment pathways and immune infiltrates were explored by single-cell RNA sequencing and TIMER. Loxl1-related changes in tumor viability/proliferation and invasion were further validated by CCK-8, western blot, wound healing, and Transwell invasion assays. Results GBM patients with altered LOXs had poor survival. Upregulated LOXs were found in IDH1-wildtype and mesenchymal (not Loxl1) GBM subtypes, promoting ECM receptor interactions in GBM. The Loxl1-based nomogram and the PRSM showed high accuracy, reliability, and net clinical benefits. Loxl1 expression was related to tumor invasion and immune infiltration (B cells, neutrophils, and dendritic cells). Loxl1 knockdown suppressed GBM cell proliferation and invasion by inhibiting the EMT pathway (through the downregulation of N-cadherin/Vimentin/Snai1 and the upregulation of E-cadherin). Conclusion The Loxl1-based nomogram and PRSM were stable and individualized for assessing GBM patient prognosis, and the invasive role of Loxl1 could provide a promising therapeutic strategy.

In this research, the extraction process of polysaccharides from Pithecellobium clypearia Benth (PCBPs) was optimized using dual-frequency ultrasound-assisted extraction (DUAE). The biological activities of PCBPs were investigated by in vitro antioxidant, hypoglycemic, and anti-hyperlipidemic assay. High-performance anion-exchange chromatography, high-performance gel permeation chromatography, SEM, UV–Vis spectroscopy, and FT-IR spectra were used to analyze the monosaccharide composition, molecular weight, microscopic morphology, and characteristic structure of PCBPs. The results showed that the maximum extraction rate of PCBPs was 9.90 ± 0.16% when the ultrasonic time was 8 min, the liquid-to-material ratio was 32 mL/g, and the ultrasonic power was 510 W. The PCBPs also possessed excellent in vitro antioxidant, hypoglycemic, and anti-hyperlipidemic activities. In addition, the average molecular weight of PCBPs was 15.07 kDa. PCBPs consisted of rhamnose, arabinose, galactose, glucose, xylose, mannose, and glucuronic acid, with the molar ratios of 11.07%, 18.54%, 48.17%, 10.44%, 4.62%, 4.96%, and 2.20%, respectively. Moreover, the results of SEM showed that PCBPs mainly showed a fine spherical mesh structure. The above studies provided a valuable theoretical basis for the subsequent in-depth study of PCBPs.

Litsea cubeba essential oil (LCEO) has garnered widespread attention due to its robust biological activity. However, challenges such as high volatility, limited water solubility, and low bioavailability impede its application. Nano-emulsion encapsulation technology offers an effective solution to these issues. In this study, we prepared litsea cubeba essential oil nano-emulsion (LCEO-NE) for the first time using whey protein (WP) as the emulsifier through an ultrasonic-assisted method, achieving high efficiency with minimal energy consumption. Transmission electron microscopy and dynamic light scattering analyses revealed that the nanoparticles were uniformly spherical, with a particle size of 183.5 ± 1.19 nm and a zeta potential of −35.5 ± 0.95 mV. Stability studies revealed that LCEO-NE exhibited excellent thermal and salt stability, maintaining its integrity for up to four weeks when stored at 4 °C and 25 °C. In vitro digestion assays confirmed the digestibility of LCEO-NE. Furthermore, evaluation of the DPPH, ABTS, and antimicrobial activities revealed that LCEO-NE displayed superior bacteriostatic and antioxidant properties compared to LCEO. Scanning electron microscopy elucidated that its bacteriostatic effect involved the disruption of bacterial microstructure. Hemocompatibility and cytotoxicity assays demonstrated the safety of LCEO-NE within the effective concentration range. This research supports the utilization of nanoparticles for encapsulating LCEO, thereby enhancing its stability and bioactivity, and consequently expanding its applications in the food and pharmaceutical industries.

Introduction: The emergence and application of generative artificial intelligence/large language models (hereafter GenAI LLMs) have the potential for significant impact on the healthcare industry. However, there is currently a lack of systematic research on GenAI LLMs in healthcare based on reliable data. This article aims to conduct an exploratory study of the application of GenAI LLMs (i.e., ChatGPT) in healthcare from the perspective of digital media (i.e., online news), including the application scenarios, potential opportunities, and challenges. Methods: This research used thematic qualitative text analysis in five steps: firstly, developing main topical categories based on relevant articles; secondly, encoding the search keywords using these categories; thirdly, conducting searches for news articles via Google ; fourthly, encoding the sub-categories using the elaborate category system; and finally, conducting category-based analysis and presenting the results. Natural language processing techniques, including the TermRaider and AntConc tool, were applied in the aforementioned steps to assist in text qualitative analysis. Additionally, this study built a framework, using for analyzing the above three topics, from the perspective of five different stakeholders, including healthcare demanders and providers. Results: This study summarizes 26 applications (e.g., provide medical advice, provide diagnosis and triage recommendations, provide mental health support, etc.), 21 opportunities (e.g., make healthcare more accessible, reduce healthcare costs, improve patients care, etc.), and 17 challenges (e.g., generate inaccurate/misleading/wrong answers, raise privacy concerns, lack of transparency, etc.), and analyzes the reasons for the formation of these key items and the links between the three research topics. Conclusions: The application of GenAI LLMs in healthcare is primarily focused on transforming the way healthcare demanders access medical services (i.e., making it more intelligent, refined, and humane) and optimizing the processes through which healthcare providers offer medical services (i.e., simplifying, ensuring timeliness, and reducing errors). As the application becomes more widespread and deepens, GenAI LLMs is expected to have a revolutionary impact on traditional healthcare service models, but it also inevitably raises ethical and security concerns. Furthermore, GenAI LLMs applied in healthcare is still in the initial stage, which can be accelerated from a specific healthcare field (e.g., mental health) or a specific mechanism (e.g., GenAI LLMs’ economic benefits allocation mechanism applied to healthcare) with empirical or clinical research.

Abstract Traumatic brain injury (TBI) is a common trauma with high mortality and disability rates worldwide. However, the current management of this disease is still unsatisfactory. Therefore, it is necessary to investigate the pathophysiological mechanisms of TBI in depth to improve the treatment options. In recent decades, abundant evidence has highlighted the significance of endoplasmic reticulum stress (ERS) in advancing central nervous system (CNS) disorders, including TBI. ERS following TBI leads to the accumulation of unfolded proteins, initiating the unfolded protein response (UPR). Protein kinase RNA-like ER kinase (PERK), inositol-requiring protein 1 (IRE1), and activating transcription factor 6 (ATF6) are the three major pathways of UPR initiation that determine whether a cell survives or dies. This review focuses on the dual effects of ERS on TBI and discusses the underlying mechanisms. It is suggested that ERS may crosstalk with a series of molecular cascade responses, such as mitochondrial dysfunction, oxidative stress, neuroinflammation, autophagy, and cell death, and is thus involved in the progression of secondary injury after TBI. Hence, ERS is a promising candidate for the management of TBI.

AbstractThe color of the leaves is one of the most important factors for horticultural crops that are considered by breeders, and is also attracting more and more attention from economists and academics. 'Quanhong poplar’ (QHP), a rare, bright reddish-purple color-leaf cultivar that has been widely cultivated in China as a landscape tree, is a very precious color-leaf cultivar. In the present study, a reference-based assembly was performed using whole-genome sequencing data to characterize the chloroplast genome of 'QHP'. The total chloroplast genome size of ‘QHP’ is 156,950 bp, which is divided into two inverted repeat structures of 27,649 bp each, a small single-copy region of 16,563 bp, and a large single-copy region (LSC) of 85,089 bp. From the chloroplast genome, 130 genes have been predicted, including 85 protein-coding genes, 37 tRNA genes, and eight rRNA genes. A chloroplast genome containing 36.68% GC content was detected in 'QHP'. Three SNP sites have been developed between 'QHP' and Populus deltoides Zhonglin 2025. Based on the phylogenetic analysis of chloroplast genomes reported for Populus, the chloroplast of 'QHP' is closest to several strains of Populus deltoides.

Abstract Background The importance of communicating the anterior chamber and vitreous cavity for managing malignant glaucoma (MG) is widely recognized. This study investigated the impact of improved minimally invasive anterior vitrectomy (IAV) on the prognosis of MG. Methods This retrospective interventional study included patients with MG who underwent conventional surgery or improved minimally IAV in Nanchang Aier Eye Hospital between January 2011 and April 2021. For the improved step, a small amount of triamcinolone acetonide was injected into the vicinity of the iris. Then, the residual vitreous body adhering to triamcinolone acetonide was excised. Comparisons were made using repeated measures ANOVA, t-test, and chi-squared test. Results Thirty-one eyes from 26 patients were included: 15 eyes from 13 patients in the conventional group and 16 eyes from 13 patients in the IAV group. The 1-week, 1-month, and 3-month intraocular pressure (IOP) and the 3-month mean central anterior chamber depth were comparable between the two groups (all P > 0.05). The conventional group showed one eye with intraoperative vitreous hemorrhage and two eyes with postoperative re-shallowing of the anterior chamber; such events did not occur in the IAV group, and none developed corneal endothelial decompensation, IOL deviation, suprachoroidal hemorrhage, or retinal detachment during treatment and follow-up. Conclusion Patients with MG who undergo improved minimally IAV might have similar postoperative IOP and central anterior chamber depth compared with conventional surgery but with reduced complications such as intraoperative vitreous hemorrhage and postoperative re-shallowing of the anterior chamber. Improved minimally IAV might be an alternative surgery for MG.

To investigate the characteristics of rotating detonation waves fueled by liquid kerosene with increasing equivalence ratios, the experiments were performed through increasing the supply of liquid kerosene under three different mass flow rates of oxidizer. Various mode transitions were realized, including transition from unstable detonation to stable single-wave mode, transition from unstable detonation to stable double-wave mode and transition from double-wave mode to single-wave & double-wave hybrid mode. The results demonstrate that the increase of equivalence ratios leads to the improvement of mixture reactivity under lean-fuel limit, which enhances the propagation stability and pressure peak of rotating detonation waves, and then results in the transition from unstable detonation to a stable propagation mode. In addition, when the mass flow rate of oxidizer is approximately 1100 g/s, the transition from double-wave mode to single-wave & double-wave hybrid mode is observed by increasing the equivalence ratio from 0.6 to 0.93. It is concluded that the mutation of dynamic balance between the RDW and injection plenum caused by the increasing of equivalence ratio is one of the reasons inducing the mode transition. This work illustrates the feasibility of modulating the propagation mode in rotating detonation waves fueled by liquid kerosene, and promotes the application of rotating detonation engine.

Numerous studies have shown that explosive sequence loads can cause serious damage to underwater vehicles, especially the bubble surge in the later stage of the explosion, which poses a huge threat to the internal structure of the vehicle. This study explores the damage characteristics of cylindrical shell structures under complete sequence loads based on the Arbitrary Lagrangian–Eulerian (ALE) method. By conducting experiments on the surge characteristics near the damaged plate under explosive action and comparing them with numerical results, the effectiveness of the method is verified. Subsequently, the damage characteristics of single- and double-layered cylindrical shell structures under underwater explosion sequence loads (shock waves, bubbles, surges) were explored, and the failure modes of cylindrical shell structures under various loads were summarized. The results indicate that the damage of shock waves to single-layer cylindrical shell structures is most severe at a blast distance of 0.5 m. For double-layer cylindrical shells, increasing the blast distance will reduce the impact of bubble surge on the pressure-resistant shell. The stress and strain in the central area of the pressure-resistant shell also decrease, and the deflection and Z-direction velocity also decrease accordingly. This study laid the foundation for enhancing the impact resistance of underwater vehicles.

Drug prediction and treatment using bioinformatics and large-scale modeling have emerged as pivotal research areas. This study proposes a novel multi-level collaboration framework named Syn-COM for feature extraction and data integration of diseases and drugs. The framework aims to explore optimal drug combinations and interactions by integrating molecular virtuality, similarity clustering, overlap area, and network distance. It uniquely combines the characteristics of Chinese herbal medicine with clinical experience and innovatively assesses drug interaction and correlation through a synergy matrix. Gouty arthritis (GA) was used as a case study to validate the framework’s reliability, leading to the identification of an effective drug combination for GA treatment, comprising Tamaricis Cacumen (Si = 0.73), Cuscutae Semen (Si = 0.68), Artemisiae Annuae Herba (Si = 0.62), Schizonepetae Herba (Si = 0.73), Gleditsiae Spina (Si = 0.89), Prunellae Spica (Si = 0.75), and Achyranthis Bidentatae Radix (Si = 0.62). The efficacy of the identified drug combination was confirmed through animal experiments and traditional Chinese medicine (TCM) component analysis. Results demonstrated significant reductions in the blood inflammatory factors IL1A, IL6, and uric acid, as well as downregulation of TGFB1, PTGS2, and MMP3 expression (p < 0.05), along with improvements in ankle joint swelling in GA mice. This drug combination notably enhances therapeutic outcomes in GA by targeting key genes, underscoring the potential of integrating traditional medicine with modern bioinformatics for effective disease treatment.

The atmosphere is a complex nonlinear system, with the information of its temperature, water vapor, pressure, and cloud being crucial aspects of remote-sensing data analysis. There exist intricate interactions among these internal components, such as convection, radiation, and humidity exchange. Atmospheric phenomena span multiple spatial and temporal scales, from small-scale thunderstorms to large-scale events like El Niño. The dynamic interactions across different scales, along with external disturbances to the atmospheric system, such as variations in solar radiation and Earth surface conditions, contribute to the chaotic nature of the atmosphere, making long-term predictions challenging. Grasping the intrinsic chaotic dynamics is essential for advancing atmospheric analysis, which holds profound implications for enhancing meteorological forecasts, mitigating disaster risks, and safeguarding ecological systems. To validate the chaotic nature of the atmosphere, this paper reviewed the definitions and main features of chaotic systems, elucidated the method of phase space reconstruction centered on Takens’ theorem, and categorized the qualitative and quantitative methods for determining the chaotic nature of time series data. Among quantitative methods, the Wolf method is used to calculate the Largest Lyapunov Exponents, while the G–P method is used to calculate the correlation dimensions. A new method named Improved Saturated Correlation Dimension method was proposed to address the subjectivity and noise sensitivity inherent in the traditional G–P method. Subsequently, the Largest Lyapunov Exponents and saturated correlation dimensions were utilized to conduct a quantitative analysis of FY-4A and Himawari-8 remote-sensing infrared observation data, and ERA5 reanalysis data. For both short-term remote-sensing data and long-term reanalysis data, the results showed that more than 99.91% of the regional points have corresponding sequences with positive Largest Lyapunov exponents and all the regional points have correlation dimensions that tended to saturate at values greater than 1 with increasing embedding dimensions, thereby proving that the atmospheric system exhibits chaotic properties on both short and long temporal scales, with extreme sensitivity to initial conditions. This conclusion provided a theoretical foundation for the short-term prediction of atmospheric infrared radiation field variables and the detection of weak, time-sensitive signals in complex atmospheric environments.

Growth performance is an important economic trait of broilers but the related serum metabolomics remains unclear. In this study, we utilized non-targeted metabolomics using ultra-high-performance liquid phase tandem mass spectrometry (UHPLC-MS/MS) to establish metabolite profiling in the serum of Chinese Wumeng black-bone chickens. The biomarker metabolites in serum associated with growth performance of chickens were identified by comparing the serum metabolome differences between chickens that significantly differed in their weights at 160 days of age when fed identical diets. A total of 766 metabolites were identified including 13 differential metabolite classes such as lipids and lipid-like molecules, organic acids and their derivatives, and organoheterocyclic compounds. The results of difference analysis using a partial least squares discriminant analysis (PLS-DA) model indicated that the low-body-weight group could be differentiated based on inflammatory markers including prostaglandin a2, kynurenic acid and fatty acid esters of hydroxy fatty acids (FAHFA), and inflammation-related metabolic pathways including tryptophan and arachidonic acid metabolism. In contrast, the sera of high-body-weight chickens were enriched for riboflavin and 2-isopropylmalic acid and for metabolic pathways including riboflavin metabolism, acetyl group transfer into mitochondria, and the tricarboxylic acid (TCA) cycle. These results provide new insights into the practical application of improving the growth performance of local chickens.

ObjectiveRecent research suggests a potential link between the gut microbiome (GM) and epilepsy. We undertook a Mendelian randomization (MR) study to determine the possible causal influence of GM on epilepsy and its various subtypes, and explore whether cytokines act as mediators.MethodsWe utilized Genome-Wide Association Study (GWAS) summary statistics to examine the causal relationships between GM, cytokines, and four epilepsy subtypes. Furthermore, we assessed whether cytokines mediate the relationship between GM and epilepsy. Significant GMs were further investigated using transcriptomic MR analysis with genes mapped from the FUMA GWAS. Sensitivity analyses and reverse MR were conducted for validation, and false discovery rate (FDR) correction was applied for multiple comparisons.ResultsWe pinpointed causal relationships between 30 GMs and various epilepsy subtypes. Notably, the Family Veillonellaceae (OR:1.03, 95%CI:1.02–1.05, p = 0.0003) consistently showed a strong positive association with child absence epilepsy, and this causal association endured even after FDR correction (p-FDR

Starting from the consideration of the structure of human milk fat globule (MFG), this study aimed to investigate the effects of ultrasonic treatment on milk fat globule membrane (MFGM) and soy lecithin (SL) complexes and their role in mimicking human MFG emulsions. Ultrasonic power significantly affected the structure of the MFGM-SL complex, further promoting the unfolding of the molecular structure of the protein, and then increased solubility and surface hydrophobicity. Furthermore, the microstructure of mimicking MFG emulsions without sonication was unevenly distributed, and the average droplet diameter was large. After ultrasonic treatment, the droplets of the emulsion were more uniformly dispersed, the particle size was smaller, and the emulsification properties and stability were improved to varying degrees. Especially when the ultrasonic power was 300 W, the mimicking MFG emulsion had the highest encapsulation rate and emulsion activity index and emulsion stability index were increased by 60.88 % and 117.74 %, respectively. From the microstructure, it was observed that the spherical droplets of the mimicking MFG emulsion after appropriate ultrasonic treatment remain well separated without obvious flocculation. This study can provide a reference for the screening of milk fat globules mimicking membrane materials and the further utilization and development of ultrasound in infant formula.

ABSTRACT: To develop effective antibiotics alternatives is getting more and more important to poultry healthy production. The study investigated the effects of a microencapsulated essential oils and organic acids preparation (EOA) on growth performance, slaughter performance, nutrient digestibility and intestinal microenvironment of broilers. A total of 624 1-day-old male Arbor Acres broilers were randomly divided into 6 groups including the control group (T1) fed with basal diet, the antibiotic group (T2) supplemented with basal diet with 45 mg/kg bacitracin methylene disalicylate (BMD), and 4 inclusion levels of EOA-treated groups (T3, T4, T5, T6 groups) chickens given basal diet with 200, 400, 600, and 800 mg EOA/kg of diet, respectively. Results showed that compared with the control, the 200 mg/kg EOA group increased average daily gain (ADG) and average body weight (ABW) during the early stage (P < 0.05). EOA addition decreased crypt depth of the ileum (P < 0.05), but villus height to crypt depth ratio was increased by EOA addition at 200 and 400 mg/kg at d 21 (P < 0.05). Compared with the control, dietary addition EOA at 200, 400 and 600 mg/kg increased the lipase activity in the duodenum at d 21 (P < 0.05). Increased lactic acid bacteria population was found in cecal digesta of the 400 mg/kg EOA group at d 21 (P < 0.05), and higher concentration of butyric acid level was observed in cecal digesta at d 21 and d 42 in the 200 mg/kg EOA group compared with the control (P < 0.05). RT-PCR analysis found that dietary EOA addition decreased the gene expression of IL-1β, COX-2 and TGF-β4 in the ileum at d 21 (P < 0.05), while only the 200 mg/kg EOA increased the gene expression of IL-10, TGF-β4, Claudin-1, ZO-1, CATH-1, CATH-3, AvBD-1, AvBD-9 and AvBD-12 in the ileum at d 42 (P < 0.05) compared with the control. In summary, adding 200 mg/kg and 400 mg/kg of the EOA to the diet could improve the growth performance and intestinal microenvironment through improving intestinal morphology, increasing digestive enzymes activity and cecal lactic acid bacteria abundance and butyric acid content, improving intestinal barrier function as well as maintaining intestinal immune homeostasis. The improving effect induced by EOA addition in the early growth stage was better than that in the later growth stage. Overall, the EOA product might be an effective antibiotic alternative for broiler industry.

Objectives: Multi-Criteria Decision Analysis (MCDA) has gained increasing attention in supporting drug risk-benefit assessment, pricing and reimbursement, as well as optimization of clinical interventions. The objective of this study was to systematically collect and categorize evaluation criteria and techniques of weighting and scoring of MCDA for drug value assessment.Methods: A systematic review of the literature was conducted across seven databases to identify articles utilizing the MCDA frameworks for the evaluation of drug value. Evaluation criteria mentioned in the included studies were extracted and assigned to 5 dimensions including clinical, economic, innovative, societal and humanistic value. A descriptive statistical analysis was performed on the identified drug value evaluation criteria, as well as the weighting and scoring techniques employed. The more a criterion or technique were mentioned in articles, the more important we consider it.Results: Out of the 82 articles included, 111 unique criteria were identified to evaluate the value of drug. Among the 56 unique criteria (448 times) used to measure clinical value, the most frequently mentioned were “comparative safety/tolerability” (58 times), “comparative effectiveness/efficacy” (56 times), “comparative patient-perceived health/patient reported outcomes” (37 times), “disease severity” (34 times), and “unmet needs” (25 times). Regarding economic value measurement, out of the 20 unique criteria (124 times), the most frequently utilized criteria were “cost of intervention” (17 times), “comparative other medical costs” (16 times), and “comparative non-medical costs” (18 times). Out of the 10 criteria (18 times) for assessing innovative value, “a novel pharmacological mechanism” was the most frequently mentioned criterion (5 times). Among the 22 criteria (73 times) used to measure societal value, “system capacity and appropriate use of intervention” was the most frequently cited criterion (14 times). Out of the 3 criteria (15 times) utilized to measure humanistic value, “political/historical/cultural context” was the most frequently mentioned criterion (9 times). Furthermore, 11 scoring and 11 weighting techniques were found from various MCDA frameworks. “Swing weighting” and “a direct rating scale” were the most frequently used techniques in included articles.Conclusion: This study comprehensively presented the current evaluation dimensions, criteria, and techniques for scoring and weighting in drug-oriented MCDA articles. By highlighting the frequently cited evaluation criteria and techniques for scoring and weighting, this analysis will provide a foundation to reasonably select appropriate evaluation criteria and technique in constructing the MCDA framework that aligns with research objectives.

BackgroundPrevious studies suggests that gut microbiomes are associated with the formation and progression of aneurysms. However, the causal association between them remains unclear.MethodsA two-sample Mendelian randomization was conducted to investigate whether gut microbiomes have a causal effect on the risk of intracerebral aneurysm (IA), thoracic aortic aneurysm (TAA) and abdominal aortic aneurysm (AAA), and aortic aneurysm (AA). Single nucleotide polymorphisms (SNPs) smaller than the locus-wide significance level (1 × 10−5) were selected as instrumental variables. We used inverse-variance weighted (IVW) test as the primary method for the evaluation of causal association. MR-Egger, weighted median, weighted mode, and MR Pleiotropy Residual Sum and Outlier (MR-PRESSO) methods were conducted for sensitive analysis. The p-value was adjusted by the false discovery rate (FDR) which adjust the results of multiple comparisons, a p < 0.05 and q < 0.1 was considered a significant causal association. Additionally, a p < 0.05 and q > 0.1 was considered a suggestive causal effect. Additionally, reverse MR was also performed to exclude the possibility of reverse causality.ResultsThe phylum Firmicutes (OR = 0.62; 95% CI, 0.48–0.81), class Lentisphaeria (OR = 0.75; 95% CI, 0.62–0.89), and order Victivallales (OR = 0.75; 95% CI, 0.62–0.89) have a causal protective effect on the risk of AAA. Additionally, class Verrucomicrobia, class Deltaproteobacteria, order Verrucomicrobiale, family Verrucomicrobiacea, genus Eubacterium rectale group, genus Akkermansia, and genus Clostridium innocuum group were negatively associated with the risk of different types of aneurysms, whereas class Negativicutes, order Selenomonadales, and genus Roseburia had positive causal association with different types of aneurysms (p < 0.05; q > 0.1). Further sensitivity analysis validated the robustness of our MR results, and no reverse causality was found with these gut microbiomes (p > 0.05).ConclusionOur MR analysis confirmed the causal association of specific gut microbiomes with AAA, and these microbiomes were considered as protective factors. Our result may provide novel insights and theoretical basis for the prevention of aneurysms through regulation of gut microbiomes.

Summary: Cell fate conversion is associated with extensive post-translational modifications (PTMs) and architectural changes of sub-organelles, yet how these events are interconnected remains unknown. We report here the identification of a phosphorylation code in 14-3-3 binding motifs (PC14-3-3) that greatly stimulates induced cardiomyocyte (iCM) formation from fibroblasts. PC14-3-3 is identified in pivotal functional proteins for iCM reprogramming, including transcription factors and chromatin modifiers. Akt1 kinase and protein phosphatase 2A are the key writer and key eraser of the PC14-3-3 code, respectively. PC14-3-3 activation induces iCM formation with the presence of only Tbx5. In contrast, PC14-3-3 inhibition by mutagenesis or inhibitor-mediated code removal abolishes reprogramming. We discover that key PC14-3-3-embedded factors, such as histone deacetylase 4 (Hdac4), Mef2c, and Foxo1, form Hdac4-organized inhibitory nuclear condensates. PC14-3-3 activation disrupts Hdac4 condensates to promote cardiac gene expression. Our study suggests that sub-organelle dynamics regulated by a PTM code could be a general mechanism for stimulating cell reprogramming.

Background: Dietary nutrient intake contributes to urination; however, the association between dietary nutrient intake, especially that of fat, and urinary incontinence (UI) is not well understood. The most common types of UI include stress UI (SUI) and urgency UI (UUI). Objective: To investigate the potential effect(s) of dietary fat intake on UI and explore its mechanism of action in relation to body mass index (BMI). Methods: A cross-sectional survey of data from 15,121 individuals (20–85 years of age) from the National Health and Nutrition Examination Survey (2001–2008), a random population-based sample, was performed. Data regarding dietary nutrient intake were collected through 24 h dietary recall interviews. UI and covariate data were collected through in-person interviews. UI was assessed according to the American Urological Association Symptom Index. The odds ratio (OR) for SUI and UUI were calculated using multivariate logistic regression analysis. The mediation effect was estimated using observational mediation analysis. Results: Higher total fat intake was positively associated with increased odds for developing UI (OR 1.44 [95% confidence interval (CI) 1.08–1.93]). Females who consumed more saturated fatty acids (SFA), monounsaturated fatty acids (MUFA), and polyunsaturated fatty acids (PUFA) were more likely to develop SUI. BMI partially explained the association between total fat, SFA, MUFA, and PUFA and SUI; the proportions of the mediation effect of BMI were 14.7%, 13.0%, 18.7%, and 16.3%, respectively. Conclusions: Results of this study emphasize the key role of dietary fat intake in the prevalence of UI. Higher fat intake was positively associated with UI and BMI partially mediated the effect of fat intake on SUI.

Abstract Background SP gene family, consisting of SP100, SP110, SP140, and SP140L, has been implicated in the initiation and advancement of numerous malignancies. Nevertheless, their clinical significance in glioma remains incompletely understood. Method Expression levels and prognostic significance of SP family members were evaluated in the TCGA and CGGA datasets. Multifactorial analysis was used to identify SP gene family members that can independently impact the prognosis of glioma patients. A SP140‐based predictive risk model/nomogram was developed in TCGA dataset and validated in CGGA dataset. The model's performance was evaluated through receiver operating characteristic (ROC) curves, calibration plots, and decision curve analyses. Phenotypic associations of SP140 and TRIM22 were examined through CancerSEA and TIMER. The effect of SP140 inhibitor in glioma progress and TRIM22/PI3K/AKT signaling pathway was confirmed in U251/U87 glioma cells. Results The SP family members exhibited elevated expression in gliomas and were negatively correlated with prognosis. SP140 emerged as an independent prognostic factor, and a SP140‐based nomogram/predictive risk model demonstrated high accuracy. SP140 inhibitor, GSK761, lead to the suppression of TRIM22 expression and the PI3K/AKT signaling pathway. GSK761 also restrain glioma proliferation, migration, and invasion. Furthermore, SP140 and TRIM22 coexpressed in glioma cells with high level of vascular proliferation, TRIM22 is closely associated with the immune cell infiltration. Conclusion SP140‐based nomogram proved to be a practical tool for predicting the survival of glioma patients. SP140 inhibitor could suppress glioma progress via TRIM22/PI3K/AKT signaling pathway.

BackgroundCurrently, disease-modifying therapies (DMTs) for progressive multiple sclerosis (PMS) are widely used in clinical practice. At the same time, there are a variety of drug options for DMTs, but the effect of the drugs that can better relieve symptoms and improve the prognosis are still inconclusive.ObjectivesThis systematic review aimed to evaluate the efficacy and safety of DMTs for PMS and to identify the best among these drugs.MethodsMEDLINE, EMBASE, the Cochrane Library, and clinicaltrials.gov were systematically searched to identify relevant studies published before 30 January, 2023. We assessed the certainty of the evidence using the confidence in the network meta-analysis (CINeMA) framework. We estimated the summary risk ratio (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes with 95% credible intervals (CrIs).ResultsWe included 18 randomized controlled trials (RCTs) involving 9,234 patients in the study. DMT can effectively control the disease progression of MS. Among them, mitoxantrone, siponimod, and ocrelizumab are superior to other drug options in delaying disease progression (high certainty). Mitoxantrone was the best (with high certainty) for mitigating deterioration (progression of disability). Ocrelizumab performed best on the pre- and post-treatment Timed 25-Foot Walk test (T25FW; low certainty), as did all other agents (RR range: 1.12–1.05). In the 9-Hole Peg Test (9HPT), natalizumab performed the best (high certainty), as did all other agents (RR range: 1.59–1.09). In terms of imaging, IFN-beta-1b performed better on the new T2 hypointense lesion on contrast, before and after treatment (high certainty), while siponimod performed best on the change from baseline in the total volume of lesions on T2-weighted image contrast before and after treatment (high certainty), and sWASO had the highest area under the curve (SUCRA) value (100%). In terms of adverse events (AEs), rituximab (RR 1.01), and laquinimod (RR 1.02) were more effective than the placebo (high certainty). In terms of serious adverse events (SAEs), natalizumab (RR 1.09), and ocrelizumab (RR 1.07) were safer than placebo (high certainty).ConclusionDMTs can effectively control disease progression and reduce disease deterioration during the treatment of PMS.Systematic review registrationhttps://inplasy.com/?s=202320071, identifier: 202320071.