Search

Abstract Background Acute lung injury or acute respiratory distress syndrome (ALI/ARDS) is a devastating clinical syndrome with high incidence and mortality rates. IRE1α-XBP1 pathway is one of the three major signaling axes of endoplasmic reticulum stress that is involved in inflammation, metabolism, and immunity. The role and potential mechanisms of IRE1α-XBP1 axis in ALI/ARDS has not well understood. Methods The ALI murine model was established by intratracheal administration of lipopolysaccharide (LPS). Hematoxylin and eosin (H&E) staining and analysis of bronchoalveolar lavage fluid (BALF) were used to evaluate degree of lung injury. Inflammatory responses were assessed by ELISA and RT-PCR. Apoptosis was evaluated using TUNEL staining and western blot. Moreover, western blot, immunohistochemistry, and immunofluorescence were applied to test expression of IRE1α, XBP1, NLRP3, TXNIP, IL-1β, ERK1/2 and NF-κB p65. Results The expression of IRE1α significantly increased after 24 h of LPS treatment. Inhibition of the IRE1α-XBP1 axis with 4µ8C notably improved LPS-induced lung injury and inflammatory infiltration, reduced the levels of IL-6, IL-1β, and TNF-α, and decreased cell apoptosis as well as the activation of the NLRP3 inflammasome. Besides, in LPS-stimulated Beas-2B cells, both 4µ8C and knockdown of XBP1 diminished the mRNA levels of IL-6 and IL-1B, inhibited cell apoptosis and reduced the protein levels of TXNIP, NLRP3 and secreted IL-1β. Mechanically, the phosphorylation and nuclear translocation of ERK1/2 and p65 were significantly suppressed by 4µ8C and XBP1 knockdown. Conclusions In summary, our findings suggest that IRE1α-XBP1 axis is crucial in the pathogenesis of ALI/ARDS, whose suppression could mitigate the pulmonary inflammatory response and cell apoptosis in ALI through the TXNIP/NLRP3 inflammasome and ERK/p65 signaling pathway. Our study may provide new evidence that IRE1α-XBP1 may be a promising therapeutic target for ALI/ARDS.

Abstract Background To investigate the impact of optic disc torsion (ODT), horizontal disc tilt (HDT) angle, and ovality index (OI) on different retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL) segments in healthy myopic eyes. Methods ODT and OI were measured from fundus photographs. HDT angle, peripapillary RNFL, and macular GCIPL were measured by swept-source optical coherence tomography (SS-OCT). The association between optic disc morphology and the RNFL/GCIPL thickness were evaluated, with age and axial length (AL) adjusted. Results Among 530 healthy myopic eyes of 284 participants (mean age: 41.7 years, mean spherical equivalent: − 7.70 D, and mean AL: 26.6 mm), 335 eyes (63.2%) had temporal disc torsion (temporal group) and 195 eyes (36.8%) had nasal disc torsion (nasal group). For the nasal group, a larger OI was associated with thinner superior-to-superonasal GCIPL (β = − 7.465 to − 6.972, both P = 0.024) and temporal RNFL sectors (β = − 49.596 to − 27.748, P ≤ 0.014). For the temporal group, a larger OI was associated with thinner superior-to-nasal (β = − 50.255 to − 22.093, P ≤ 0.006) and thicker temporal RNFL sectors (β = 29.015 to 56.890, P ≤ 0.003). Additionally, a larger HDT angle was associated with thinner superior-to-nasal RNFL sectors (β = − 0.559 to − 0.242, P ≤ 0.036) and thinner superior-to-superotemporal GCIPL sectors (β = − 0.084 to − 0.069, P ≤ 0.037). Conclusions The optic disc tortional direction was associated with the measurement of different RNFL and GCIPL sectors independent of the AL and age. These should be considered when constructing a myopic normative database.

Abstract In the era of synthetic biology, design, construction, and utilization of synthetic chromosomes with unique features provide a strategy to study complex cellular processes such as aging. Herein, we successfully construct the 884 Kb synXIII of Saccharomyces cerevisiae to investigate replicative aging using these synthetic strains. We verify that up-regulation of a rRNA-related transcriptional factor, RRN9, positively influence replicative lifespan. Using SCRaMbLE system that enables inducible whole-genome rearrangement on synXIII, we obtain 20 SCRaMbLEd synXIII strains with extended lifespan. Transcriptome analysis reveal the expression of genes involve in global protein synthesis is up-regulated in longer-lived strains. We establish causal links between genotypic change and the long-lived phenotype via reconstruction of some key structural variations observed in post-SCRaMbLE strains and further demonstrate combinatorial effects of multiple aging regulators on lifespan extension. Our findings underscore the potential of synthetic yeasts in unveiling the function of aging-related genes.

Objective To evaluate the diagnostic value of total serum immunoglobulin E （IgE） levels， eosinophil （EOS） count and percentage in the diagnosis of allergic rhinitis （AR）， and to construct a diagnostic model for preliminary diagnosis of AR by combining total serum IgE and EOS. Methods Clinical data of 305 AR patients and 256 non-AR patients admitted to Department of Otolaryngology at the First Affiliated Hospital of Chongqing Medical University from April 2023 to April 2024 were retrospectively analyzed. The general information， total serum IgE level， EOS count and percentage were compared between two groups. Binary logistic regression analysis was used to screen for suitable indicators to construct the predictive model， and the receiver operating characteristic （ROC） curve was plotted. The area under the ROC curve （AUC） was used to determine the predictive value of this model. Clinical data from 216 patients with and without AR admitted to Department of Otolaryngology at the First Affiliated Hospital of Chongqing Medical University from June 2019 to June 2022 were collected for external validation. Stratification analysis was performed according to age [adolescent group （≤ 18 years old）， youth group （19-45 years old）， middle-aged group （46-60 years old）， and elderly group （> 60 years old）]， respectively. Results The percentage of EOS and total serum IgE level were the influencing factors of AR in the overall and all age groups. The combined diagnostic model for all patients was： Logit P = -4.174+6.856EOS count+ 0.048total serum IgE. Diagnostic model in adolescent group was： Logit P = -4.472+0.637EOS percentage+0.034total serum IgE； youth group： Logit P = -4.491+0.372EOS percentage+0.068total serum IgE； middle-aged group： Logit P = -4.759+5.768EOS count+ 0.062total serum IgE； elderly group： Logit P = -4.888+0.855EOS percentage+0.028total serum IgE， respectively. Hosmer-Lemeshow goodness-of-fit test， ROC curve analysis and external validation all indicated that this model had high diagnostic value. Conclusion The combination of total serum IgE levels and EOS count demonstrates good diagnostic value for AR in different age groups， which can be used to guide preliminary diagnosis of AR.

Based on the oil and gas exploration in western depression of the Qaidam Basin, NW China, combined with the geochemical, seismic, logging and drilling data, the basic geological conditions, oil and gas distribution characteristics, reservoir-forming dynamics, and hydrocarbon accumulation model of the Paleogene whole petroleum system (WPS) in the western depression of the Qaidam Basin are systematically studied. A globally unique ultra-thick mountain-style WPS is found in the western depression of the Qaidam Basin. Around the source rocks of the upper member of the Paleogene Lower Ganchaigou Formation, the structural reservoir, lithological reservoir, shale oil and shale gas are laterally distributed in an orderly manner and vertically overlapped from the edge to the central part of the lake basin. The Paleogene WPS in the western depression of the Qaidam Basin is believed unique in three aspects. First, the source rocks with low organic matter abundance are characterized by low carbon and rich hydrogen, showing a strong hydrocarbon generating capacity per unit mass of organic carbon. Second, the saline lake basinal deposits are ultra-thick, with mixed deposits dominating the center of the depression, and strong vertical and lateral heterogeneity of lithofacies and storage spaces. Third, the strong transformation induced by strike-slip compression during the Himalayan resulted in the heterogeneous enrichment of oil and gas in the mountain-style WPS. As a result of the coordinated evolution of source-reservoir-caprock assemblage and conducting system, the Paleogene WPS has the characteristics of “whole process” hydrocarbon generation of source rocks which are low-carbon and hydrogen-rich, “whole depression” ultra-thick reservoir sedimentation, “all direction” hydrocarbon adjustment by strike-slip compressional fault, and “whole succession” distribution of conventional and unconventional oil and gas. Due to the severe Himalayan tectonic movement, the western depression of the Qaidam Basin evolved from depression to uplift. Shale oil is widely distributed in the central lacustrine basin. In the sedimentary system deeper than 2 000 m, oil and gas are continuous in the laminated limy-dolomites within the source rocks and the alga limestones neighboring the source kitchen, with intercrystalline pores, lamina fractures in dolomites and fault-dissolution bodies serving as the effective storage space. All these findings are helpful to supplement and expand the WPS theory in the continental lake basins in China, and provide theoretical guidance and technical support for oil and gas exploration in the Qaidam Basin.

Abstract Bitter gourd wilt, a severe vascular disease triggered by the soilborne pathogen Fusarium oxysporum f. sp. momordicae (FOM), markedly constrains bitter gourd yield. In this study, a novel strain BF19 of Brevibacillus brevis was isolated and identified, exhibiting strong antimicrobial activity against FOM through in vivo and in vitro experiments. To comprehensively assess the biocontrol potential of strain BF19, we conducted phenotypic, phylogenetic, and comparative genomics analyses. Phenotypic analysis revealed that BF19 exhibited 53.33% biocontrol efficacy and significantly increased the average plant height, root fresh weight, and dry weight. Whole-genome sequencing and comparative genomic analysis revealed numerous potential genes associated with biocontrol mechanisms in BF19. Importantly, the integration of metabolic cluster prediction with liquid chromatography‒tandem mass spectrometry (LC‒MS/MS) revealed the presence of a macrobrevin antibiotic, a product of polyketide synthases (PKSs), predominantly in BF19 fermentation products. The effectiveness of the Br. brevis strain BF19 and its crude extract against bitter gourd wilt has also been confirmed. This study provides a genetic framework for future investigations on PKSs and establishes a scientific basis for optimizing field applications of microbial biopesticides derived from Br. brevis BF19.

Abstract Psoriasis is a chronic inflammatory skin disorder with multiple causes, including genetic and environmental factors. Despite advances in treatment, there remains a need to identify novel therapeutic targets. A Mendelian randomization (MR) analysis was conducted to identify therapeutic targets for psoriasis. Data on cis-expression quantitative trait loci were obtained from the eQTLGen Consortium (n = 31,684). Summary statistics for psoriasis (outcome) were sourced from the GWAS Catalog with a sample size of 484,598, including 5,427 cases and 479,171 controls. Colocalization analysis was used to assess whether psoriasis risk and gene expression were driven by shared single nucleotide polymorphisms. Drug prediction and molecular docking were utilized to validate the pharmacological value of the drug targets. The MR analysis found that 81 drug targets were significantly associated, and two (TYK2 and PRSS36) were supported by colocalization analysis (PP.H4 > 0.80). Phenome-wide association studies did not show any associations with other traits at the gene level. Biologically, these genes were closely related to immune function. Molecular docking revealed strong binding with drugs and proteins, as supported by available structural data. This study validated TYK2 as a drug target for psoriasis, in line with its existing clinical use, including the development of decucravacitinib. PRSS36 is a potential novel target requiring further investigation.

Abstract Rain is a common weather phenomenon, and the challenge of removing rain streaks from a single image is crucial due to its detrimental impact on image quality and the extraction of valuable background information. Existing methods commonly rely on specific assumptions regarding rain models, which restricts their ability to accommodate a wide range of real-world scenarios. To overcome this limitation, these methods often require complex optimization techniques or stepwise refinement strategies. In this paper, we propose a novel wide rectangular regional block and dual attention complementary enhancement deraining kernel prediction subnet to meet the challenge. The network called WRRDANet consists of a kernel prediction subnet and pixel-wise dilation filtering. In the kernel prediction subnet, we capture more specific contextual background information and complex pixel-wise kernels. Afterward, the learned pixel-wise multi-scale kernels from the kernel prediction subnet are used to perform dilation filtering on the original rainy image, effectively restoring richer background details by expanding the scope of deraining to a larger extent. We conducted a comprehensive evaluation using synthetic and real rainfall datasets to demonstrate the effectiveness of our approach. The results, both qualitatively and quantitatively, indicate that our approach outperforms other popular rain removal methods.

Abstract Teratoma, due to its remarkable ability to differentiate into multiple cell lineages, is a valuable model for studying human embryonic development. The similarity of the gene expression and chromatin accessibility patterns in these cells to those observed in vivo further underscores its potential as a research tool. Notably, teratomas derived from human naïve (pre-implantation epiblast-like) pluripotent stem cells (PSCs) have larger embryonic cell diversity and contain extraembryonic lineages, making them more suitable to study developmental processes. However, the cell type-specific epigenetic profiles of naïve PSC teratomas have not been yet characterized. Using single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq), we analyzed 66,384 cell profiles from five teratomas derived from human naïve PSCs and their post-implantation epiblast-like (primed) counterparts. We observed 17 distinct cell types from both embryonic and extraembryonic lineages, resembling the corresponding cell types in human fetal tissues. Additionally, we identified key transcription factors specific to different cell types. Our dataset provides a resource for investigating gene regulatory programs in a relevant model of human embryonic development.

Purpose: To evaluate the diagnosis performance of digital mammography (DM) and digital breast tomosynthesis (DBT), DM combined DBT with AI-based strategies for breast mass ≤ 2 cm. Materials and methods: DM and DBT images in 483 patients including 512 breast masses were acquired from November 2018 to November 2019. Malignant and benign tumours were determined by biopsies using histological analysis and follow-up within 24 months. The radiomics and deep learning methods were employed to extract the breast mass features in images and finally for benign and malignant classification. The DM, DBT and DM combined DBT (DM + DBT) images were fed into radiomics and deep learning models to construct corresponding models, respectively. The area under the receiver operating characteristic curve (AUC) was employed to estimate model performance. An external dataset of 146 patients from March 2021 to December 2022 from another center was enrolled for external validation. Results: In the internal testing dataset, compared with the DM model and the DBT model, the DM + DBT models based on radiomics and deep learning both showed statistically significant higher AUCs [0.810 (RA-DM), 0.823 (RA-DBT) and 0.869 (RA-DM + DBT), P ≤ 0.001; 0.867 (DL-DM), 0.871 (DL-DBT) and 0.908 (DL-DM + DBT), P = 0.001]. The deep learning models present superior to the radiomics models in the experiments with only DM (0.867 vs 0.810, P = 0.001), only DBT (0.871 vs 0.823, P = 0.001) and DM + DBT (0.908 vs 0.869, P = 0.003). Conclusions: DBT has a clear additional value for diagnosing breast mass less than 2 cm compared with only DM. AI-based methods, especially deep learning, can help achieve excellent performance.

ABSTRACTIn this study, we used high-throughput sequencing technology to analyze the diversity and predict gene function of intestinal bacteria from captive black-capped capuchin in two wildlife parks. The results showed that the composition of intestinal gut bacterial diversity was significantly higher in black-capped capuchins monkeys from ES than HT. Moreover, high similarity of intestinal bacteria of black-capped capuchins at the same site was found by sample stratum clustering. Black-capped capuchins intestinal bacteria can be clustered into 2296 ASVs, belonging to 16 phyla, 99 families and 210 genera, respectively. The dominant phyla were Bacteroidota and Firmicutes in the intestinal bacteria of black-capped capuchins, but there were differences in the dominant bacterial families and dominant bacterial genera between ES and HT, and the bacterial families with significant differences had correspondence with bacterial genera. The results provide a basis for the study of intestinal bacteria in black-capped capuchins and the isolation and purification of dominant bacteria. The results of this study fill the gap in the study of intestinal bacterial diversity and its gene functions in black-capped capuchins, and provide a reference for the isolation of dominant bacteria in black-capped capuchins’ intestinal microbes and the discovery and study of novel functional genes.

Background: The concurrent effects of particulate matter (PM) on both blood pressure (BP) and short-chain fatty acids (SCFAs) are insufficiently explored, with limited research on the potential mediating roles of SCFAs. Methods: In this prospective panel study with 4 follow-ups, we recruited 40 college students in Hefei, China, to assess the impacts of short-term exposure to PM (aerodynamic diameter ≤10 μm (PM10), ≤2.5 μm (PM2.5), and ≤1 μm (PM1)) on BP and SCFAs, along with potential mechanisms. Real-time PM data, urinary SCFAs levels, and BP indicators were systematically collected. Linear mixed-effects models assessed the relationships between PM, SCFAs, and BP. Mediation analyses explored SCFAs’ mediating role in the PM-BP association. Results: PM exposure was positively linked to BP and negatively associated with SCFAs. For a 10 μg/m3 rise in PM10 at lag 0–72 h, there were notable reductions of 0.0019 % (95 %CI: −0.0028, −0.0010) in Acetic acid, 0.0262 % (-0.0369, −0.0155) in Propionic acid, and 0.0702 % (-0.1025, −0.0378) in Butyric acid. Systolic BP, diastolic BP, and mean arterial pressure (MAP) increased by 2.60 mmHg (0.96, 4.25), 2.24 mmHg (1.18, 3.31), and 2.36 mmHg (1.20, 3.53), respectively, per 10-μg/m3 rise in PM1 at lag 0–24 h. Decreased SCFAs levels explained significant portions (24.69–31.80 %) of the elevated MAP due to PM10. Stronger associations were found in females and individuals with abnormal BMI. Conclusions: Our study shows that PM exposure decreases urinary SCFAs levels, which partially mediate the impact of PM on elevated BP. These findings enhance our comprehension of the pathways linking PM exposure to BP changes.

The advent of midazolam holds profound implications for modern clinical practice. The hypnotic and sedative effects of midazolam afford it broad clinical applicability. However, the specific mechanisms underlying the modulation of altered consciousness by midazolam remain elusive. Herein, using pharmacology, optogenetics, chemogenetics, fiber photometry, and gene knockdown, this in vivo research revealed the role of locus coeruleus (LC)-ventrolateral preoptic nucleus noradrenergic neural circuit in regulating midazolam-induced altered consciousness. This effect was mediated by α1 adrenergic receptors. Moreover, gamma-aminobutyric acid receptor type A (GABAA-R) represents a mechanistically crucial binding site in the LC for midazolam. These findings will provide novel insights into the neural circuit mechanisms underlying the recovery of consciousness after midazolam administration and will help guide the timing of clinical dosing and propose effective intervention targets for timely recovery from midazolam-induced loss of consciousness.

ABSTRACT Acanthamoeba species are among the most common free-living amoeba and ubiquitous protozoa, mainly distributed in water and soil, and cause Acanthamoeba keratitis (AK) and severe visual impairment in patients. Although several studies have reported genomic characteristics of Acanthamoeba, limited sample sizes and sources have resulted in an incomplete understanding of the genetic diversity of Acanthamoeba from different sources. While endosymbionts exert a significant influence on the phenotypes of Acanthamoeba, including pathogenicity, virulence, and drug resistance, the species diversity and functional characterization remain largely unexplored. Herein, our study sequenced and analyzed the whole genomes of 19 Acanthamoeba pathogenic strains that cause AK, and by integrating publicly available genomes, we sampled 29 Acanthamoeba strains from ocular, environmental, and other sources. Combined pan-genomic and comparative functional analyses revealed genetic differences and evolutionary relationships among the different sources of Acanthamoeba, as well as classification into multiple functional groups, with ocular isolates in particular showing significant differences that may account for differences in pathogenicity. Phylogenetic and rhizome gene mosaic analyses of ocular Acanthamoeba strains suggested that genomic exchanges between Acanthamoeba and endosymbionts, particularly potential antimicrobial resistance genes trafficking including the adeF, amrA, and amrB genes exchange events, potentially contribute to Acanthamoeba drug resistance. In conclusion, this study elucidated the adaptation of Acanthamoeba to different ecological niches and the influence of gene exchange on the evolution of ocular Acanthamoeba genome, guiding the clinical diagnosis and treatment of AK and laying a theoretical groundwork for developing novel therapeutic approaches.IMPORTANCEAcanthamoeba causes a serious blinding keratopathy, Acanthamoeba keratitis, which is currently under-recognized by clinicians. In this study, we analyzed 48 strains of Acanthamoeba using a whole-genome approach, revealing differences in pathogenicity and function between strains of different origins. Horizontal transfer events of antimicrobial resistance genes can help provide guidance as potential biomarkers for the treatment of specific Acanthamoeba keratitis cases.

We study dual AGN host galaxy morphologies at $z=2$ using the ASTRID simulation, selecting black hole (BH) pairs with small separation ($\Delta r10^7M_\odot$), and luminosity ($L_{\text{bol,12}}>10^{43}\rm{erg/s}$). We kinematically decompose (using MORDOR) $\sim1000$ dual AGN hosts into standard components - a 'disk' (thin and thick disk, pseudo-bulge) and 'bulge' (bulge and halo) and define disk-dominated galaxies by the disk-to-total $D/T\geq0.5$. In ASTRID, $60.9\pm2.1\%$ of dual AGN hosts (independent of separation) are disk-dominated, with the $D/T$ distribution peaking at $\sim0.7$. In dual-AGN hosts, the $D/T$ increases from $\sim17\% $ at $M_{\rm *}\sim 10^{9} M_{\odot}$ to $ 64\% $ for $M_{\rm *} \sim 10^{11.5} M_{\odot}$, and the pseudo-bulge is the dominant component of the disk fraction at the high mass end. Moreover, dual AGN hosts exhibit a higher fraction of disk/large pseudo-bulge than single-AGN hosts. The Disk-to-Total ratio is approximately constant with BH mass or AGN luminosity. We also create mock images of dual AGN host galaxies, employing morphological fitting software Statmorph to calculate morphological parameters and compare them with our kinematic decomposition results. Around $83.3\pm2.4\%$ of galaxies display disk-like profiles, of which $\sim60.7\pm2.2\%$ are kinematically confirmed as disks. Se\'rsic indices and half-mass radii of dual AGN host galaxies align with observational measurements from HST at $z\sim2$. Around $34\%$ are identified as mergers from the $\text{Gini}-M_{20}$ relation. We find two dual AGN hosted by galaxies that exhibit disk-like se\'rsic index $n_{12}0.5$, which are in remarkable agreement with properties of recently discovered dual quasars in disk galaxies at $z\sim 2$.

ObjectiveTo explore the association between representative insulin resistance (IR) indices and the risk of kidney stone disease in an American adult population. The representative IR indices referred to metabolic score for IR (METS-IR), triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, triglyceride glucose-body mass index (TyG-BMI), visceral adiposity index (VAI), and homeostatic model assessment of IR (HOMA-IR).MethodsWe investigated adult participants who joined the 2015–2018 National Health and Nutrition Examination Survey (NHANES) and reported kidney stone histories. Weighted proportions, multivariable regression analysis, and restricted cubic splines were used to evaluate the associations between IR indices and kidney stones after their adjustment for gender, age, race, education, smoking status, alcohol drinking frequency, hypertension and diabetes status, physical activity level, water intake, and levels of calcium, cholesterol, and uric acid.ResultsA total of 19,225 participants were included. The weighted prevalence of kidney stone was 11.1%. A multivariable logistic regression model showed a dose–response relationship between the METS-IR and kidney stone [odds ratio (OR) = 1.02, 95% confidence interval (CI) (1.01, 1.04), p

Catenary optics enables metasurfaces with higher efficiency and wider bandwidth, and is highly anticipated in the imaging system, super-resolution lithography, and broadband absorbers. However, the periodic boundary approximation without considering aperiodic electromagnetic crosstalk poses challenges for catenary optical devices to reach their performance limits. Here, perfect control of both local geometric and propagation phases is realized through field-driven optimization, in which the field distribution is calculated under real boundary conditions. Different from other optimization methods requiring a mass of iterations, the proposed design method requires less than ten iterations to get the efficiency close to the optimal value. Based on the library of shape-optimized catenary structures, centimeter-scale devices can be designed in ten seconds, with the performance improved by ~15%. Furthermore, this method has the ability to extend catenary-like continuous structures to arbitrary polarization, including both linear and elliptical polarizations, which is difficult to achieve with traditional design methods. It provides a way for the development of catenary optics and serves as a potent tool for constructing high-performance optical devices.

Abstract Repeated and widespread use of single chemical pesticides raises concerns about efficiency and safety, developing multi-component synergistic pesticides provides a new route for efficient control of diseases. Most commercial compound formulations are open systems with non-adjustable released rates, resulting in a high frequency of applications. Meanwhile, although nano pesticide delivery systems constructed with different carrier materials have been extensively studied, realizing their actual scale-up production still has important practical significance due to the large-scale field application. In this study, a boscalid and pyraclostrobin dual-loaded nano pesticide system (BPDN) was constructed with industrial-grade carrier materials to facilitate the realization of large-scale production. The optimal industrial-scale preparation mechanism of BPDN was studied with surfactants as key factors. When agricultural emulsifier No.600 and polycarboxylate are used as the ratio of 1:2 in the preparation process, the BPDN has a spherical structure with an average size of 270 nm and exhibits superior physical stability. Compared with commercial formulation, BPDN maintains rate-stabilized release up to 5 times longer, exhibits better dispersion and spreading performance on foliar, has more than 20% higher deposition amounts, and reduces loss. A single application of BPDN could efficiently control tomato gray mold during the growing period of tomatoes due to extended duration and combinatory effectiveness, reducing two application times and labor costs. Toxicology tests on various objects systematically demonstrated that BPDN has improved safety for HepG2 cells, and nontarget organism earthworms. This research provides insight into creating safe, efficient, and environmentally friendly pesticide production to reduce manual operation times and labor costs. Accompanied by production strategies that can be easily scaled up industrially, this contributes to the efficient use of resources for sustainable agriculture.

Patients with chronic lymphocytic leukemia (CLL) respond well to initial treatment with the Bcell lymphoma 2 (BCL2) inhibitor venetoclax. Upon relapse, they often retain sensitivity to BCL2 targeting, but durability of response remains a concern. We hypothesize that targeting both BCL2 and B-cell lymphoma-extra large (BCLXL) will be a successful strategy to treat CLL, including for patients who relapse on venetoclax. To test this hypothesis, we conducted a pre-clinical investigation of LP-118, a highly potent inhibitor of BCL2 with moderate BCLXL inhibition to minimize platelet toxicity. This study demonstrated that LP-118 induces efficient BAK activation, cytochrome C release, and apoptosis in both venetoclax naïve and resistant CLL cells. Significantly, LP-118 is effective in cell lines expressing the BCL2 G101V mutation and in cells expressing BCLXL but lacking BCL2 dependence. Using an immunocompetent mouse model, Eμ-TCL1, LP-118 demonstrates low platelet toxicity, which hampered earlier BCLXL inhibitors. Finally, LP-118 in the RS4;11 and OSU-CLL xenograft models results in decreases in tumor burden and survival advantage, respectively. These results provide a mechanistic rationale for the evaluation of LP-118 for the treatment of venetoclax responsive and relapsed CLL.

In light of the escalating accumulation of polymer waste in daily life, chemical recycling of polymers and value-added utilization of products have gained considerable attention in recent years. Researchers have widely explored the potential of bis(2-hydroxyethyl) terephthalate (BHET) derived from the glycolysis recycling of poly(ethylene terephthalate) (PET) waste in the synthesis of polymers or concrete. In this study, we synthesized BHET through glycolysis recycling of PET, and combined it with microencapsulated ammonium polyphosphate (Si[O.sub.2]@APP) and carboxymethyl chitosan to design a series of intumescent flame-retardant waterborne polyurethane (IFRWPU). The synergistic effect of BHET and Si[O.sub.2]([alpha])APP was demonstrated, and the resulting IFRWPU with 12.5 wt% IFR and 3 wt% BHET achieved a limit oxygen index of 25.8% and a 73%> reduction in the peak heat release rate in flame retardancy tests. Furthermore, the interaction of BHET and flame retardant was discussed using the analysis of char residue and pyrolytic gas. Overall, this work provides a novel strategy to construct superior flame-retarded waterborne polyurethane with admirable bonding performance. Highlights * The application of glycolysis product of PET in the flame-retardant modification of WPU. * The synergistic enhancement of flame retardancy between BHET and IFR was confirmed. * The intumescent flame-retardant was composed of Si[O.sub.2]([alpha])APP and CMOS. KEYWORDS char residue, flame-retardant modification, intumescent flame retardant, PET waste, waterborne polyurethane composites, 1 | INTRODUCTION As one of the commercially important polymers, polyethylene terephthalate (PET) has been widely consumed in the fields of food packaging, fibers, films, substrates, and electrical insulation materials [...]

Mepiquat chloride (1,1-dimethyl piperidinium chloride, DPC) is a representative plant growth regulator which can regulate the source-sink relationship for yield increase and shape ideal plant type for mechanical cultivation. Here we show a DPC adsorbed layered double hydroxide (DPC-LDH) architecture with enhanced controlled release property and soil distribution. By drip irrigation on cotton, it makes total dosage of DPC reduced from 270 to 90 g/ha, while the frequency decreased from 5 to 2 times. The unique supramolecular interaction is confirmed as the basis of controlled release behavior. Moreover, except for the physical resistance to the sedimentation brought by the lamellar LDH, the enhanced electrostatic interaction makes DPC-LDH the dominant distribution in soil. It improves the efficiency of DPC molecules absorbed by cotton plants and greatly saves the inputs in labor and chemicals. This method is expected to achieve the yield increase and agricultural sustainability by energy saving and emission reduction.

Abstract Skin diseases pose significant challenges in China. Internet health forums offer a platform for millions of users to discuss skin diseases and share images for early intervention, leaving large amount of valuable dermatology images. However, data quality and annotation challenges limit the potential of these resources for developing diagnostic models. In this study, we proposed a deep-learning model that utilized unannotated dermatology images from diverse online sources. We adopted a contrastive learning approach to learn general representations from unlabeled images and fine-tuned the model on coarsely annotated images from Internet forums. Our model classified 22 common skin diseases. To improve annotation quality, we used a clustering method with a small set of standardized validation images. We tested the model on images collected by 33 experienced dermatologists from 15 tertiary hospitals and achieved a 45.05% top-1 accuracy, outperforming the published baseline model by 3%. Accuracy increased with additional validation images, reaching 49.64% with 50 images per category. Our model also demonstrated transferability to new tasks, such as detecting monkeypox, with a 61.76% top-1 accuracy using only 50 additional images in the training process. We also tested our model on benchmark datasets to show the generalization ability. Our findings highlight the potential of unannotated images from online forums for future dermatology applications and demonstrate the effectiveness of our model for early diagnosis and potential outbreak mitigation.

Abstract To evaluate the midterm efficacy of the Castor stent (CS) versus in situ fenestration (ISF) for reconstructing the left subclavian artery (LSA) in patients with type B aortic dissection (TBAD). Between July 2017 and July 2022, a total of 247 patients with TBAD were enrolled. One hundred thirty‐seven patients were treated using CSs (group A), while the remaining 110 patients received ISFs (group B). Data of the two groups were retrospectively analyzed. The success rates of surgery were 99.3% and 95.5% in groups A and B (p = .053), There were no deaths during hospitalization. During surgery, group B showed a longer surgical duration [68.0 (66.0, 77.0) vs. 62.0 (59.0, 66.0) min, p

Abstract Coupling high-capacity cathode and Li-anode with solid-state electrolyte has been demonstrated as an effective strategy for increasing the energy densities and safety of rechargeable batteries. However, the limited ion conductivity, the large interfacial resistance, and unconstrained Li-dendrite growth hinder the application of solid-state Li-metal batteries. Here, a poly(ether-urethane)-based solid-state polymer electrolyte with self-healing capability is designed to reduce the interfacial resistance and provides a high-performance solid-state Li-metal battery. With its dynamic covalent disulfide bonds and hydrogen bonds, the proposed solid-state polymer electrolyte exhibits excellent interfacial self-healing ability and maintains good interfacial contact. Full cells are assembled with the two integrated electrodes/electrolytes. As a result, the Li||Li symmetric cells exhibit stable long-term cycling for more than 6000 h, and the solid-state Li-S battery shows a prolonged cycling life of 700 cycles at 0.3 C. The use of ultrasound imaging technology shows that the interfacial contact of the integrated structure is much better than those of traditional laminated structure. This work provides an interesting interfacial dual-integrated strategy for designing high-performance solid-state Li-metal batteries.

Remote sensing technology has found extensive application in agriculture, providing critical data for analysis. The advancement of semantic segmentation models significantly enhances the utilization of point cloud data, offering innovative technical support for modern horticulture in nursery environments, particularly in the area of plant cultivation. Semantic segmentation results aid in obtaining tree components, like canopies and trunks, and detailed data on tree growth environments. However, obtaining precise semantic segmentation results from large-scale areas can be challenging due to the vast number of points involved. Therefore, this paper introduces an improved model aimed at achieving superior performance for large-scale points. The model incorporates direction angles between points to improve local feature extraction and ensure rotational invariance. It also uses geometric and relative distance information for better adjustment of different neighboring point features. An external attention module extracts global spatial features, and an upsampling feature adjustment strategy integrates features from the encoder and decoder. A specialized dataset was created from real nursery environments for experiments. Results show that the improved model surpasses several point-based models, achieving a Mean Intersection over Union (mIoU) of 87.18%. This enhances the precision of nursery environment analysis and supports the advancement of autonomous nursery managements.

Abstract The development of highly active, reusable catalysts for aqueous‐phase reactions is challenging. Herein, metallic nickel is encapsulated in a nitrogen‐doped carbon–silica composite (SiO2@Ni@NC) as a catalyst for the selective hydrogenation of vanillin in aqueous media. The constructed catalyst achieved 99.8% vanillin conversion and 100% 4‐hydroxymethyl‐2‐methoxyphenol selectivity at room temperature. Based on combined scanning transmission electron microscopy, X‐ray photoelectron spectroscopy, and Raman analyses, the satisfactory catalytic performance is attributed to the composite structure consisting of an active metal, carbon, and silica. The hydrophilic silica core promoted dispersion of the catalyst in aqueous media. Moreover, the external hydrophobic NC layer has multiple functions, including preventing oxidation or leaching of the internal metal, acting as a reducing agent to reduce the internal metal, regulating the active‐site microenvironment by enriching the concentrations of H2 and organic reactants, and modifying the electronic structure of the active metal via metal–support interactions. Density functional theory calculations indicated that NC facilitates vanillin adsorption and hydrogen dissociation to promote aqueous‐phase hydrogenation. This study provides an efficient strategy for constructing encapsulated Ni‐based amphiphilic catalysts to upgrade biomass‐derived compounds.

2,4-dichlorophenol (2,4-DCP), 2,5-DCP, 2,4,5-trichlorophenol (2,4,5-TCP), 2,4,6-TCP, and ortho-phenylphenol (OPP) are widely present in the environment. However, their associations with risk and prognosis of diabetes and prediabetes remains unclear. We investigated the associations of these five phenols with the risk of diabetes and prediabetes, and with all-cause and cardiovascular disease (CVD) mortality, in adults with diabetes or prediabetes (n=6419). Information on diabetes and prediabetes indicators, and mortality data was collected from the National Health and Nutrition Examination Survey. Logistic and Cox regression models were used to explore the associations of the five phenols with risk and prognosis of diabetes and prediabetes. Participants in the highest urinary 2,4-DCP and 2,5-DCP tertiles had higher odds of diabetes [adjusted odds ratio (aOR), 1.34, 95 % confidence interval (CI): 1.10, 1.62; aOR, 1.29, 95 % CI: 1.07, 1.56, respectively] than those in the lowest tertiles. Participants with urinary OPP concentrations above the limit of detection (LOD), but below median had an aOR of 1.25 (95 % CI: 1.08, 1.46) for prediabetes compared to those with concentrations below the LOD. In adults with diabetes, the highest 2,4-DCP and 2,5-DCP tertiles were associated with all-cause mortality [adjusted hazard ratio (aHR), 1.49; 95 % CI: 1.08, 2.06; aHR, 1.49; 95 % CI: 1.08, 2.05, respectively] and CVD mortality (aHR, 2.58; 95 % CI: 1.33, 4.97; aHR, 1.96; 95 % CI: 1.06, 3.60, respectively) compared with the lowest tertiles. Compared with 2,4,5-TCP concentrations below the LOD, those above median were associated with all-cause mortality (aHR: 1.75; 95 % CI: 1.24, 2.48) and CVD mortality (aHR: 2.34; 95 % CI: 1.19, 4.63) in adults with prediabetes. Furthermore, the associations between these phenols and mortality were strengthened in some subgroups. Environmental exposure to 2,4-DCP, 2,5-DCP, 2,4,5-TCP, and OPP increases the risk or adverse prognosis of diabetes or prediabetes in adults in the US. Further studies are required to confirm these findings.

Background Nonylphenol (NP) is widely recognized as a crucial environmental endocrine-disrupting chemical and persistent toxic substance. The remediation of NP-contaminated sites primarily relies on biological degradation. Compound microbial products, as opposed to pure strains, possess a greater variety of metabolic pathways and can thrive in a wider range of environmental conditions. This characteristic is believed to facilitate the synergistic degradation of pollutants. Limited research has been conducted to thoroughly examine the potential compatibility of compound microbial agents with indigenous microflora, their ability to function effectively in practical environments, their capacity to enhance the dissipation of NP, and their potential to improve soil physicochemical and biological characteristics. Methods In order to efficiently eliminate NP in contaminated soil in an eco-friendly manner, a simulation study was conducted to investigate the impact of bioaugmentation using the functional compound microbial agent NP-M2 at varying concentrations (50 and 200 mg/L) on the dynamics of the soil microbial community. The treatments were set as follows: sterilized soil with 50 mg/kg NP (CK50) or 200 mg/kg NP (CK200); non-sterilized soil with 50 mg/kg NP (TU50) or 200 mg/kg NP (TU200); non-sterilized soil with the compound microbial agent NP-M2 at 50 mg/kg NP (J50) or 200 mg/kg NP (J200). Full-length 16S rRNA analysis was performed using the PacBio Sequel II platform. Results Both the indigenous microbes (TU50 and TU200 treatments) and the application of NP-M2 (J50 and J200 treatments) exhibited rapid NP removal, with removal rates ranging from 93% to 99%. The application of NP-M2 further accelerated the degradation rate of NP for a subtle lag period. Although the different treatments had minimal impacts on the soil bacterial α-diversity, they significantly altered the β-diversity and composition of the bacterial community. The dominant phyla were Proteobacteria (35.54%–44.14%), Acidobacteria (13.55%–17.07%), Planctomycetes (10.78%–11.42%), Bacteroidetes (5.60%–10.74%), and Actinobacteria (6.44%–8.68%). The core species were Luteitalea_pratensis, Pyrinomonas_methylaliphatogenes, Fimbriiglobus_ruber, Longimicrobium_terrae, and Massilia_sp003590855. The bacterial community structure and taxon distribution in polluted soils were significantly influenced by the activities of soil catalase, sucrase, and polyphenol oxidase, which were identified as the major environmental factors. Notably, the concentration of NP and, to a lesser extent, the compound microbial agent NP-M2 were found to cause major shifts in the bacterial community. This study highlights the importance of conducting bioremediation experiments in conjunction with microbiome assessment to better understand the impact of bioaugmentation/biostimulation on the potential functions of complex microbial communities present in contaminated soils, which is essential for bioremediation success.

Potato soft rot caused by Pectobacterium spp. are devastating diseases of potato which cause severe economic losses worldwide. Pectobacterium brasiliense is considered as one of the most virulent species. However, the virulence mechanisms and pathogenicity factors of this strain have not been fully elucidated. Here, through pathogenicity screening, we identified two Pectobacterium brasiliense isolates, SM and DQ, with distinct pathogenicity levels. SM exhibits higher virulence compared to DQ in inducing aerial stem rot, blackleg and tuber soft rot. Our genomic and transcriptomic analyses revealed that SM encodes strain specific genes with regard to plant cell wall degradation and express higher level of genes associated with bacterial motility and secretion systems. Our plate assays verified higher pectinase, cellulase, and protease activities, as well as fast swimming and swarming motility in SM. Importantly, a unique endoglucanase S specific to SM was identified. Expression of this cellulase in DQ greatly enhances its virulence compared to wild type strain. Our study sheds light on possible determinants causing different pathogenicity of Pectobacterium brasiliense species with close evolutionary distance and provides new insight into the direction of genome evolution in response to host variation and environmental stimuli.

BackgroundChronic kidney disease (CKD) is a common public health problem, which is characterized as impairment of renal function. The associations between blood metabolites and renal function remained unclear. This study aimed to assess the causal effect of various circulation metabolites on renal function based on metabolomics.MethodsWe performed a two-sample Mendelian randomization (MR) analysis to estimate the causality of genetically determined metabolites on renal function. A genome-wide association study (GWAS) of 486 metabolites was used as the exposure, while summary-level data for creatinine-based estimated glomerular filtration rate (eGFR) or CKD occurrence were set the outcomes. Inverse variance weighted (IVW) was used for primary causality analysis and other methods including weight median, MR-egger, and MR-PRESSO were applied as complementary analysis. Cochran Q test, MR-Egger intercept test, MR-PRESSO global test and leave-one-out analysis were used for sensitivity analysis. For the identified metabolites, reverse MR analysis, linkage disequilibrium score (LDSC) regression and multivariable MR (MVMR) analysis were performed for further evaluation. The causality of the identified metabolites on renal function was further validated using GWAS data for cystatin-C-based eGFR. All statistical analyses were performed in R software.ResultsIn this MR analysis, a total of 44 suggestive associations corresponding to 34 known metabolites were observed. After complementary analysis and sensitivity analysis, robust causative associations between two metabolites (betaine and N-acetylornithine) and renal function were identified. Reverse MR analysis showed no causal effects of renal function on betaine and N-acetylornithine. MVMR analysis revealed that genetically predicted betaine and N-acetylornithine could directly influence independently of each other. The causal effects of betaine and N-acetylornithine were also found on cystatin-C-based eGFR.ConclusionOur study provided evidence to support the causal effects of betaine and N-acetylornithine on renal function. These findings required further investigations to conduct mechanism exploration and drug target selection of these identified metabolites.

Studies in the past decade have shown that lipid droplets stored in liver cells under starvation are encapsulated by autophagosomes and fused to lysosomes via the endocytic system. Autophagy responds to a variety of environmental factors inside and outside the cell, so it has a complex signal regulation network. To this end, we first explored the role of Hedgehog (Hh) in autophagy and lipid metabolism. Treatment of normal mouse liver cells with SAG and GDC-0449 revealed elevated phosphorylation of AMP-activated protein kinase (AMPK) and increased lipidation of LC3. SAG, and GDC-0449 were agonist and antagonist of Smoothened (Smo) in canonical Hh pathway, respectively, but they played a consistent role in the regulation of autophagy in hepatocytes. Moreover, SAG and GDC-0449 did not affect the expression of glioma-associated oncogene (Gli1) and patched 1, suggesting the absence of canonical Hh signaling in hepatocytes. We further knocked down the Smo and found that the efects of SAG and GDC-0449 disappeared, indicating that the non-canonical Smo pathway was involved in the regulation of autophagy in hepatocytes. In addition, SAG and GDC-0449 promoted lipid degradation and inhibited lipid production signals. Knockdown of Smo slowed down the rate of lipid degradation rather than Sufu or Gli1, indicating that Hh signaling regulated the lipid metabolism via Smo. In summary, activates AMPK via Smo to promote autophagy and lipid degradation. Key words: Hh signaling, Smo, AMPK, autophagy, lipid degradation, Introduction Hedgehog (Hh) signaling, which was first identified in Drosophila, plays a vital role in embryonic development and adult stem cell self-renewal (Nusslein-Volhard and Wieschaus 1980; Ingham and McMahon 2001; [...]

Abstract Microbial production of monoterpenoid indole alkaloids (MIAs) provides a sustainable and eco‐friendly means to obtain compounds with high pharmaceutical values. However, efficient biosynthesis of MIAs in heterologous microorganisms is hindered due to low supply of key precursors such as geraniol and its derivative 8‐hydroxygeraniol catalyzed by geraniol 8‐hydroxylase (G8H). In this study, we developed a facile evolution platform to screen strains with improved yield of geraniol by using the SCRaMbLE system embedded in the Sc2.0 synthetic yeast and confirmed the causal role of relevant genomic targets. Through genome mining, we identified several G8H enzymes that perform much better than the commonly used CrG8H for 8‐hydroxygeraniol production in vivo. We further showed that the N‐terminus of these G8H enzymes plays an important role in cellular activity by swapping experiments. Finally, the combination of the engineered chassis, optimized biosynthesis pathway, and utilization of G8H led to the final strain with more than 30‐fold improvement in producing 8‐hydroxygeraniol compared with the starting strain. Overall, this study will provide insights into the construction and optimization of yeast cells for efficient biosynthesis of 8‐hydroxygeraniol and its derivatives.

Abstract To investigate the influence of different grasping postures on the hand’s skin deformation, a handheld 3D EVA SCANNER was used to obtain 3D models of 111 women in five postures, including a straight posture and grasping cylinders with various diameters (4/6/8/10 cm). Skin relaxation strain ratio ( $${\lambda }_{p}$$ λ p ) and surface area skin relaxation strain ratio ( $${\lambda }_{m}$$ λ m ) were used as measures of skin deformation between two landmarks and multiple landmarks, respectively. The effects of grasping posture on skin deformation in different directions were analyzed. The results revealed significant variations in skin deformation among different grasping postures, except for the width of middle finger metacarpal and the length of middle finger’s proximal phalanx. The $${\lambda }_{p}$$ λ p increased with decreasing grasping object diameter, ranging from 5 to 18% on the coronal axis, and from 4 to 20% on the vertical axis. The overall variation of $${\lambda }_{m}$$ λ m ranged from 5 to 37.5%, following the same trend as $${\lambda }_{p}$$ λ p except for the surface area of tiger’s mouth, which exhibited a maximum difference of 10.9% with significant differences. These findings have potential applications in improving the design of hand equipment and understanding hand movement characteristics.

Abstract Background Medical costs have been rising rapidly in recent years, and China is controlling medical costs from the perspective of health insurance payments. Objectives To explore the impact of the capitation prepayment method on medical expenses and health service utilization of coronary heart disease (CHD) patients, which provides a scientific basis for further improvement of the payment approach. Methods The diagnosis records of visits for CHD in the database from 2014 to 2016 (April to December each year) were selected, and two townships were randomly selected as the pilot and control groups. Propensity score matching (PSM) and difference-in-difference (DID) model were used to assess changes in outpatient and inpatient expenses and health service utilization among CHD patients after the implementation of the capitation prepayment policy. Results There were eventually 3,900 outpatients and 664 inpatients enrolled in this study after PSM. The DID model showed that in the first year of implementing the reform, total outpatient expenses decreased by CNY 13.953, drug expenses decreased by CNY 11.289, as well as Medicare payments decreased by CNY 8.707 in the pilot group compared to the control group. In the second year of implementing the reform, compared with the control group, the pilot group had a reduction of CNY 3.123 in other expenses, and a reduction of CNY 6.841 in Medicare payments. There was no significant change in inpatient expenses in the pilot group compared to the control group, but there was an increase of 0.829 visits to rural medical institutions, and an increase of 0.750 visits within the county for inpatients. Conclusions The capitation prepayment method has been effective in controlling the outpatient expenses of CHD patients, as well as improving the medical service capacity of medical institutions within the Medical Community, and increasing the rate of inside county visits for inpatients.

Abstract Synthetic auxotrophy in which cell viability depends on the presence of an unnatural amino acid (unAA) provides a powerful strategy to restrict unwanted propagation of genetically modified organisms (GMOs) in open environments and potentially prevent industrial espionage. Here, we describe a generic approach for robust biocontainment of budding yeast dependent on unAA. By understanding escape mechanisms, we specifically optimize our strategies by introducing designed “immunity” to the generation of amber-suppressor tRNAs and developing the transcriptional- and translational-based biocontainment switch. We further develop a fitness-oriented screening method to easily obtain multiplex safeguard strains that exhibit robust growth and undetectable escape frequency (

The complex structure of monoclonal antibodies (mAbs) expressed in Chinese hamster ovary (CHO) cells may result in the accumulation of unfolded proteins, triggering endoplasmic reticulum (ER) stress and an unfolded protein response (UPR). If the protein folding ability cannot maintain ER homeostasis, the cell will shut down protein translation and ultimately induce apoptosis. We co-overexpressed HsQSOX1b and survivin proteins in the antibody-producing cell line CHO-PAb to obtain a new cell line, CHO-PAb-QS. Compared with CHO-PAb cells, the survival time of CHO-PAb-QS cells in batch culture was extended by 2 days, and the antibody accumulation and productivity were increased by 52% and 45%, respectively. The proportion of (HC-LC)2 was approximately doubled in the CHO-PAb-QS cells, which adapted to the accelerated disulfide bond folding capacity by upregulating the UPR’s strength and increasing the ER content. The results of the apoptosis assays indicated that the CHO-PAb-QS cell line exhibited more excellent resistance to apoptosis induced by ER stress. Finally, CHO-PAb-QS cells exhibited mild oxidative stress but did not significantly alter the redox status. This study demonstrated that strategies based on HsQSOX1b and survivin co-overexpression could facilitate protein disulfide bond folding and anti-apoptosis ability, enhancing antibody production efficiency in CHO cell lines.