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Abstract Radiotherapy sensitivity is associated with the prognosis of patients with tongue squamous cell carcinoma (TSCC). In the present study, we proposed to explore the specific mechanism of interventional radiology (IR) therapy for TSCC in vitro and in vivo. TSCC cells were treated with 6 Gy IR and tumor bearing mice were treated with 20 Gy × 1 IR. DIA quantitative proteomics along with bioinformatics analysis were conducted in TSCC cells to investigate differential proteins related to IR and relation of which involved in TMEM147 and SPHK1 was confirmed by immunoprecipitation. Cell proliferation, apoptosis, autophagy& autophagy flux along with calcium signaling pathway detection were performed in vitro and in vivo. Our results showed that IR induced increasing calcium levels accompanied by up-regulated TMEM147 and down-regulated SPHK1 along with enhancing autophagy together with apoptosis. The effect of calcium overloading induced by IR on autophagy and apoptosis was dependent on increasing TMEM147 and decreasing SPHK1. However, IR-induced autophagy and apoptosis tended to be independent of only increasing calcium levels when down-regulating TMEM147 or up-regulating SPHK1 expression in vitro and in vivo. Our study suggested that calcium-mediated TMEM147/SPHK1 may promote autophagy and apoptosis to improve radiotherapy sensitivity in TSCC.

Abstract Ménière’s disease (MD) is a complex inner ear disorder characterized by a range of symptoms, with its pathogenesis linked to immune-related mechanisms. Our previous research demonstrated that IL-1β maturation and release can trigger cell pyroptosis, exacerbating the severity of the endolymphatic hydrops in a mouse model; however, the specific mechanism through which IL-1β influences MD symptoms remains unclear. This study conducted on patients with MD examined changes in protein signatures in the vestibular end organs (VO) and endolymphatic sac (ES) using mass spectrometry. Gene ontology and protein pathway analyses showed that differentially expressed proteins in the ES are closely related to adhesion, whereas those in the VO are related to synapse processes. Additionally, the study found elevated expression of Glutaminase (GLS) in the VO of MD patients compared to controls. Further investigations revealed that IL-1β increased glutamate levels by upregulating GLS expression in HEI-OC1 cells. Treatment with a GLS inhibitor or an IL-1β receptor antagonist alleviated auditory-vestibular dysfunction and reduced glutamate levels in mice with endolymphatic hydrops. These findings collectively suggest that imbalanced neurotransmitter release and immune responses contribute to the pathology of MD, potentially explaining the hearing loss and vertigo associated with the disease and offering new avenues for therapeutic interventions.

Abstract Background Epidemiological studies show inconsistent links between hearing/vision impairment and dementia risk. Using multisource data, we investigated how single or combined sensory impairments relate to risks of all-cause and specific types of dementia. Methods We employed a triangulation approach combining three methodologies. We analyzed 90,893 UK Biobank (UKB) adults to explore single and joint effects of hearing and vision impairments on all-cause and Alzheimer’s disease (AD), vascular dementia (VD) and non-AD non-VD (NAVD). A meta-analysis of prospective studies involving 937,908 participants provided stronger evidence. Finally, we conducted Mendelian randomization (MR) analysis using genome-wide association studies from UKB (361,194 participants) and FinnGen (412,181 participants) to validate relationships between sensory impairments and dementia occurrence. Results In the UKB cohort study, compared to participants with normal hearing, those in the mild and severe hearing impairment groups had progressively and significantly higher risk of all-cause dementia (mild: HR1.52, 95%CI 1.31–1.77; severe: HR1.80, 95%CI 1.36–2.38), AD (mild: HR1.63, 95%CI 1.30–2.04; severe: HR2.18, 95%CI 1.45–3.27), VD (mild: HR1.68, 95%CI 1.19–2.37; severe: HR1.47, 95%CI 1.22–1.78), and NAVD (mild: HR1.47, 95%CI 1.22–1.78; severe: HR1.98, 95%CI 1.43–2.75). Besides, vision impairment was associated with an increased risk of all-cause dementia (HR1.55, 95%CI 1.18–2.04) and NAVD (HR1.51, 95%CI 1.07–2.13). Furthermore, dual sensory impairment was associated with stepwise increased risks of all-cause and cause-specific dementia than single hearing or vision impairment. In the meta-analysis of 31 prospective cohort studies, risks of all-cause dementia and AD were elevated in participants with single hearing impairment (all-cause dementia: HR1.30, 95%CI 1.21–1.40; AD: HR1.30, 95%CI 1.21–1.40) and dual sensory impairment (all-cause dementia: HR1.63, 95%CI1.14–2.12; AD: HR 2.55, 95%CI 1.19–3.91), while single vision impairment only associated with higher risk of all-cause dementia (HR1.43, 95%CI 1.16–1.71) but not AD. Finally, the MR analysis revealed a significant association between hearing impairment and all-cause dementia (OR1.74, 95%CI 1.01–2.99), AD (OR1.56, 95%CI 1.09–2.23), and NAVD (OR1.14, 1.02–1.26), as well as vision impairment and NAVD (OR1.62, 95%CI 1.13–2.33). Conclusions Our findings showed significant associations between hearing and vision impairments and increased risks of all-cause and cause-specific dementia. Standardized hearing and vision assessment and intervention should be emphasized in dementia prevention strategies.

Abstract The respiratory system, including the lungs, is essential for terrestrial life. While recent research has advanced our understanding of lung development, much still relies on animal models and transcriptome analyses. In this study conducted within the Human Developmental Cell Atlas (HDCA) initiative, we describe the protein-level spatiotemporal organization of the lung during the first trimester of human gestation. Using high-parametric tissue imaging with a 30-plex antibody panel, we analyzed human lung samples from 6 to 13 post-conception weeks, generating data from over 2 million cells across five developmental timepoints. We present a resource detailing spatially resolved cell type composition of the developing human lung, including proliferative states, immune cell patterns, spatial arrangement traits, and their temporal evolution. This represents an extensive single-cell resolved protein-level examination of the developing human lung and provides a valuable resource for further research into the developmental roots of human respiratory health and disease.

Specialized pro-resolving lipid mediators including maresin 1 mediate resolution but the levels of these are reduced in Alzheimer’s disease brain, suggesting that they constitute a novel target for the treatment of Alzheimer’s disease to prevent/stop inflammation and combat disease pathology. Therefore, it is important to clarify whether they counteract the expression of genes and proteins induced by amyloid-β. With this objective, we analyzed the relevance of human monocyte–derived microglia for in vitro modeling of neuroinflammation and its resolution in the context of Alzheimer’s disease and investigated the pro-resolving bioactivity of maresin 1 on amyloid-β42–induced Alzheimer’s disease–like inflammation. Analysis of RNA-sequencing data and secreted proteins in supernatants from the monocyte-derived microglia showed that the monocyte-derived microglia resembled Alzheimer’s disease–like neuroinflammation in human brain microglia after incubation with amyloid-β42. Maresin 1 restored homeostasis by down-regulating inflammatory pathway related gene expression induced by amyloid-β42 in monocyte-derived microglia, protection of maresin 1 against the effects of amyloid-β42 is mediated by a re-balancing of inflammatory transcriptional networks in which modulation of gene transcription in the nuclear factor-kappa B pathway plays a major part. We pinpointed molecular targets that are associated with both neuroinflammation in Alzheimer’s disease and therapeutic targets by maresin 1. In conclusion, monocyte-derived microglia represent a relevant in vitro microglial model for studies on Alzheimer’s disease-like inflammation and drug response for individual patients. Maresin 1 ameliorates amyloid-β42–induced changes in several genes of importance in Alzheimer’s disease, highlighting its potential as a therapeutic target for Alzheimer’s disease.

Objective To investigate the clinical efficacy of preoperative therapeutic plasma exchange(TPE) in preventing acute rejection after ABO incompatible kidney transplantation(ABOi-KT). Methods Nine patients with ABOi-KT who were admitted to the renal transplant department of our hospital from April 2022 to April 2024 were retrospectively analyzed. They received a total of 28 TPEs before kidney transplantation, and the treatment plan was summarized as follows: The proportion of the substitute fluid, as well as the frequency and volume of TPE were determined based on the patient′s ABO blood group system antibody titer, gender, height, weight, hematocrit and other indicators upon admission. The patient′s relevant laboratory indicators, including hemoglobin, platelets, leukocytes, coagulation function, total protein, albumin, globulin, A/G, creatinine and urea nitrogen upon admission and after TPE were monitored and statistically analyzed. After transplantation, changes in renal function indicators such as ABO blood group system antibody titers, creatinine and urinary excretion were observed, and clinical symptoms of acute rejection, such as swelling, pain and edema in the transplanted kidney area were observed. Results Nine ABOi-KT patients had an average of about 3 TPEs before transplantation surgery, with an average total volume of approximately 2 500 mL to 3 500 mL per TPE, or approximately about 1.01 to 1.16 plasma volume (PV). After multiple TPEs, pre-transplantation antibody titers decreased by an average of 3 times compared to before TPE. There were no statistically significant differences in Hb, PLT, PT, PTA, INR, TBil, ALB, Cr and BUN (P>0.05), while statistically significant differences were found in WBC, APTT, Fbg, TP, GLB and A/G (P

Sclerostin emerges as a novel target for bone anabolic therapy in bone diseases. Osteogenesis imperfecta (OI) and X-linked hypophosphatemia (XLH) are rare bone diseases in which therapeutic potential of sclerostin inhibition cannot be ignored. In OI, genetic/pharmacologic sclerostin inhibition promoted bone formation of mice, but responses varied by genotype and age. Serum sclerostin levels were higher in young OI-I patients, while lower in adult OI-I/III/IV. It's worth investigating whether therapeutic response of OI to sclerostin inhibition could be clinically predicted by genotype and age. In XLH, preclinical/clinical data suggested factors other than identified FGF23 contributing to XLH. Higher levels of circulating sclerostin were detected in XLH. Sclerostin inhibition promoted bone formation in Hyp mice, while restored phosphate homeostasis in age-/gender-dependent manner. The role of sclerostin in regulating phosphate metabolism deserves investigation. Sclerostin/FGF23 levels of XLH patients with/without response to FGF23-antibody warrants study to develop precise sclerostin/FGF23 inhibition strategy or synergistic/additive strategy. Notably, OI patients were associated with cardiovascular abnormalities, so were XLH patients receiving conventional therapy. Targeting sclerostin loop3 promoted bone formation without cardiovascular risks. Further, blockade of sclerostin loop3-LRP4 interaction while preserving sclerostin loop2-ApoER2 interaction could be a potential precise sclerostin inhibition strategy for OI and XLH with cardiovascular safety.The Translational Potential of this Article.Preclinical data on the molecular understanding of sclerostin inhibition in OI and therapeutic efficacy in mouse models of different genotypes, as well as clinical data on serum sclerostin levels in patients with different phenotypes of OI, were reviewed and discussed. Translationally, it would facilitate to develop clinical prediction strategies (e.g. based on genotype and age, not just phenotype) for OI patients responsive to sclerostin inhibition. Both preclinical and clinical data suggested sclerostin as another factor contributing to XLH, in addition to the identified FGF23. The molecular understanding and therapeutic effects of sclerostin inhibition on both promoting bone anabolism and improving phosphate homostasis in Hyp mice were reviewed and discussed. Translationaly, it would facilitate the development of precise sclerostin/FGF23 inhibition strategy or synergistic/additive strategy for the treatment of XLH. Cardiovascular risk could not be ruled out during sclerostin inhibition treatment, especially for OI and XLH patients with cardiovascular diseases history and cardiovascular abnormalities. Studies on the role of sclerostin in inhiting bone formation and protecting cardiovascular system were reviewed and discussed. Translationaly, blockade of sclerostin loop3-LRP4 interaction while preserving sclerostin loop2-ApoER2 interaction could be a potential precise sclerostin inhibition strategy for OI and XLH with cardiovascular safety.

Improvement of cultivated cotton adaptability to extreme climate events under climate change promotes sustainable cotton production. Extreme rainfall leads to a significant decrease in cotton yield, which may be related to changes in soil water consumption (SWC) and the vertical distribution of yield, but relevant research is still scarce. Here, a two-year cotton sowing date experiment was conducted in which geostatistics, sensor technology, the spatial grid method, and principal component analysis were combined to analyze cotton utilization of soil water during extreme rainfall (2021) and normal (2022) years. The reasons for cotton yield reduction under extreme rainfall and strategies to improve cotton production adaptability to extreme rainfall were discussed. Under extreme rainfall, the morphogenesis and reproductive organ development of cotton were inhibited. The accumulation of SWC and its relationship with the biomass accumulation of cotton on different sowing dates under extreme rainfall exhibited nearly opposite characteristics to those in a normal year. Simultaneously, the two-year yield showed the opposite trend with the change in sowing date. There existed a trade-off strategy for the vertical distribution (i.e., on the upper, middle and lower fruiting branches) of cotton yield. Extreme rainfall reduced the yield at lower fruiting branches and increased the boll-forming rate of the upper fruiting branches, which was closely related to seed cotton yield, lint yield and water productivity (WP). Optimizing the cotton sowing date (early sowing should be appropriate in this study) may improve the adaptability of cotton production under extreme rainfall, but further long-term studies are needed. This study highlights the critical practice of climate-smart agriculture and has reference value for the sustainable development of cotton production.

The presence of antibiotics as emerging micropollutants in the aquatic environment has been raising health concerns for a number of years. Macrolides (MLs) are a large class of widely-used antibiotics, but there is a lack of information on their distribution and risks in surface waters across the central and western regions of China. To clearly describe the pollution characteristics and risks of MLs in Weihe River (the largest tributary of the Yellow River), analysis of 5 typical MLs was conducted using a newly developed LC−MS/MS method for 50 water samples collected over three seasons during 2021–2022. The results revealed that the area showed comparable ML concentrations with other regions worldwide. However, the ML concentrations were much lower than those in the river during 2016 from a previous study. Furthermore, concentrations exhibited significant seasonal variation, with highest concentrations in the winter. Along the main stream of the Weihe River, the sampling sites close to the wastewater treatment plants (WWTPs) and livestock farms exhibited higher concentrations of MLs, indicating the significant contribution from WWTPs and animal husbandry to the emission of MLs. The risk quotients (RQs) suggested that the ecological risks associated with MLs were most pronounced in winter among the three seasons, with erythromycin posing a high or medium risk to algae at all sampling sites. The results of this study will be of importance towards the goal of understanding the presence of these emerging contaminants in surface waters and any required risk reduction measures.

BackgroundFew studies have focused on the region-specific relationship between cardiovascular disease (CVD) and low temperature worldwide.ObjectiveWe aimed to provide an overview of trends in mortality and disability-adjusted life years (DALYs) for CVD and its subtypes attributable to low temperature over the past 30 years in 204 countries and regions, along with the associations of these trends with age, period, and birth cohorts.MethodsData on the estimated burden of CVDs (including ischemic heart disease, hypertensive heart disease, and stroke) attributable to low temperature were obtained from the Global Burden of Disease Study 2019. We utilized an age-period-cohort model to estimate overall annual percentage changes in mortality (net drifts), annual percentage changes from 15 ~ 19 to 81 ~ 85 years (local drifts), and period and cohort relative risk (period/cohort effects) between 1990 and 2019.ResultsAmong noncommunicable diseases, CVDs had the highest mortality rate and DALY loss attributable to low temperature worldwide and has increased from 65.7 to 67.3%, which is mainly attributed to the increase in East Asia and Pacific region. In terms of the level of economic and social development, an inverted U-shape was found in the age-standardized mortality rates (ASMR) due to low-temperature across different sociodemographic indices (SDI) regions. Both high CVD mortality (19.45, 95% CI [14.54, 24.17%]) and a decreasing mortality rate related to low temperature (from 1990 to 2019, net drift, −3.25% [−3.76, 2.73%] per year) was found in high SDI countries or territories, with opposite outcome found in low SDIs regions. The older adults (70+) and men share the highest rate of CVD ASMR and DALY attributed to low temperature across all regions, especially in North America and Europe and Central Asia.ConclusionMortality and DALY loss from CVD attributable to low temperature showed an overall decreasing trend globally except for East Asia and Pacific region. SDI, sex, age and geographic location contributed to the diversity of the CVD disease burden associated with low temperature worldwide. More attention should be given to the older adults, men, and low SDI regions.

Using renewable steam-exploded poplar (SEP) as carbon source, nickel metal doped carbon hybrid materials were designed to synthesize catalysts (Ni/SEP) with certain oxygen evolution reaction (OER) properties and were compared with nickel catalysts supported on metal organic framework structure (ZIF67-Ni). The roles of SEP support in Ni-based catalyst were considered. Scanning electron microscope (SEM) images confirmed that the fiber could better hinder the aggregation of metal particles. Fourier transform infrared spectroscopy (FT-IR) indicated the presence of surface OH groups after the reduction process. X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) analyses confirmed the major form of metallic Ni in the resulting Ni catalysts. Carbon materials as carriers, the synergetic effect of Ni-doped, and carbon carrier played an important role in facilitating the kinetics of OER, which was similar to the carrier of metal-organic frame material. Notably, the Ni/SEP (11.3 mF/cm-2) and ZIF67-Ni (37.2 mF/cm-2) with better OER performance exhibited a smaller double layer capacitances (Cdl), suggesting the intrinsic OER catalytic activity of the Ni/SEP and ZIF67-Ni were much higher in comparison to the ZIF67-Ni/SEP. Moreover, the inferior performance of Ni/SEP further indicated that the synergistic effect between carbon and Ni/NiO contributes to the enhanced OER activity.

Critical size bone defects represent a significant challenge worldwide, often leading to persistent pain and physical disability that profoundly impact patients’ quality of life and mental well-being. To address the intricate and complex repair processes involved in these defects, we performed single-cell RNA sequencing and revealed notable shifts in cellular populations within regenerative tissue. Specifically, we observed a decrease in progenitor lineage cells and endothelial cells, coupled with an increase in fibrotic lineage cells and pro-inflammatory cells within regenerative tissue. Furthermore, our analysis of differentially expressed genes and associated signaling pathway at the single-cell level highlighted impaired angiogenesis as a central pathway in critical size bone defects, notably influenced by reduction of Spp1 and Cxcl12 expression. This deficiency was particularly pronounced in progenitor lineage cells and myeloid lineage cells, underscoring its significance in the regeneration process. In response to these findings, we developed an innovative approach to enhance bone regeneration in critical size bone defects. Our fabrication process involves the integration of electrospun PCL fibers with electrosprayed PLGA microspheres carrying Spp1 and Cxcl12. This design allows for the gradual release of Spp1 and Cxcl12 in vitro and in vivo. To evaluate the efficacy of our approach, we locally applied PCL scaffolds loaded with Spp1 and Cxcl12 in a murine model of critical size bone defects. Our results demonstrated restored angiogenesis, accelerated bone regeneration, alleviated pain responses and improved mobility in treated mice.

Abstract Nanopore direct RNA sequencing (DRS) has emerged as a powerful tool for RNA modification identification. However, concurrently detecting multiple types of modifications in a single DRS sample remains a challenge. Here, we develop TandemMod, a transferable deep learning framework capable of detecting multiple types of RNA modifications in single DRS data. To train high-performance TandemMod models, we generate in vitro epitranscriptome datasets from cDNA libraries, containing thousands of transcripts labeled with various types of RNA modifications. We validate the performance of TandemMod on both in vitro transcripts and in vivo human cell lines, confirming its high accuracy for profiling m6A and m5C modification sites. Furthermore, we perform transfer learning for identifying other modifications such as m7G, Ψ, and inosine, significantly reducing training data size and running time without compromising performance. Finally, we apply TandemMod to identify 3 types of RNA modifications in rice grown in different environments, demonstrating its applicability across species and conditions. In summary, we provide a resource with ground-truth labels that can serve as benchmark datasets for nanopore-based modification identification methods, and TandemMod for identifying diverse RNA modifications using a single DRS sample.

Abstract Background Gastric cancer (GC) is a prevalent type of malignant gastrointestinal tumor. Many studies have shown that CENPE acts as an oncogene in some cancers. However, its expression level and clinical value in GC are not clear. Methods Obtaining clinical data information on gastric adenocarcinoma from TCGA and GEO databases. The gene expression profiling interaction analysis (GEPIA) was used to evaluate the relationship between prognosis and CENPE expression in gastric cancer patients. Utilizing the UALCAN platform, the correlation between CENPE expression and clinical parameters was examined. Functions and signaling pathways of CENPE were analyzed using the Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA). The association between immunological infiltrating cells and CENPE expression was examined using TIMER2.0. Validation was performed by real-time quantitative PCR (qPT-PCR) and immunohistochemical analysis. Results According to the analysis of the GEPIA database, the expression of CENPE is increased in gastric cancer tissues compared to normal tissues. It was also found to have an important relationship with the prognosis of the patient (p

Abstract Circular RNAs (circRNAs) are a newly appreciated type of endogenous noncoding RNAs that play vital roles in the development of various human cancers, including osteosarcoma (OS). In this study, we investigated three circRNAs (circ_0076684, circ_0003563, circ_0076691) from the RUNX Family Transcription Factor 2 (RUNX2) gene locus in OS. We found that the expression of circ_0076684, circ_0003563, circ_0076691, and RUNX2 mRNA is upregulated in OS, which is a consequence of CBX4-mediated transcriptional activation. Among these three RUNX2-circRNAs, only circ_0076684 is significantly associated with the clinical features and prognosis of OS patients. Functional experiments indicate that circ_0076684 promotes OS progression in vitro and in vivo. Circ_0076684 acts as a sponge for miR-370-3p, miR-140-3p, and miR-193a-5p, raising Cut Like Homeobox 1 (CUX1) expression by sponging these three miRNAs. Furthermore, we presented that circ_0076684 facilitates OS progression via CUX1. In conclusion, this study found that the expression of three circRNAs and RUNX2 mRNA from the RUNX2 gene locus is significantly upregulated in OS, as a result of CBX4-mediated transcriptional activation. Circ_0076684 raises CUX1 expression by sponging miR-370-3p, miR-140-3p, and miR-193a-5p, and facilitates OS progression via CUX1.

China has implemented policies to promote fuel ethanol development and achieve its dual-carbon goal. Under the policy, the significant modifications will occur in the allocation of land use resources within ethanol raw material cultivation regions. In the process of land use change, ensuring food provision and protecting the regional carbon sink are also crucial for sustainable development. This study explores carbon distribution in the Guiping section of the Yujiang River basin, where bioethanol raw materials are cultivated. Using the CLUE-S model, a multi-objective model prioritizing economic and ecological benefits is constructed. Four scenarios (i.e., the natural expansion scenario (NES); the food conservation scenario (FCS); the bioethanol feedstock conservation scenario (BCS), and the carbon sinks conservation scenario (CCS) are simulated, predicting land resource distribution by 2030. The total carbon sink decreased by 285.60 gC·m−2·a−1, showing a seasonal trend of higher levels in summer and lower levels in winter. In 2030, the total carbon sink decreased in the NES scenario, while it increased in the FCS and BCS scenarios. The CCS scenario had the largest increase, approximately 582.27 × 103 tC. These simulated scenarios consider various economic and environmental factors, providing a scientific basis for the efficient allocation of regional land resources. They also have significant implications for local energy, economic, and environmentally sustainable development, as well as promoting the achievement of carbon neutrality.

Abstract Objective To retrospectively analyze clinical features in adolescent Menière's disease (MD). Methods The medical records of adolescents with MD (11–17 years old) from May 2014 to March 2023 in Shandong Provincial ENT Hospital were retrospectively analyzed, including clinical features, a battery of auditory and vestibular function tests, sensory organization test, and imaging assessments. Patients with recurrent vertigo of childhood (RVC) were as controls. Results Compared with RVC, adolescent MD showed higher pure tone average threshold (p

ObjectiveCarnation is a plant that holds high value in terms of its edibility, medicinal properties, and ornamental appeal. Creating no sense he aim of this study was to evaluate the antioxidant and antitumor properties of extracts derived from various parts of the carnation plant. Metabolomics technology was employed to identify the primary chemical constituents.MethodsInitially, we measured the total phenolic and total flavonoid contents in carnation roots, stems, leaves, and flowers, followed by assessing the antioxidant and anti-tumor capabilities of each component using diverse experimental methods. Subsequently, UPLC-MS/MS was employed to identify metabolites in different parts of carnation and investigate their roles in antioxidant and anti-tumor activities.ResultsMention numerical value- for better underatnding- Results of the study indicated that the methanol extract obtained from carnation flowers and roots exhibited superior antioxidant capacity compared to that from the stems and leaves. This disparity may be attributed to the abundance of polyphenols, flavonoids, and antioxidants present in the flowers, including methyl ferulate and luteolin-4’-O-glucoside. Furthermore, the significant presence of the anthraquinone compound rhein-8-O-glucoside in carnation roots may contribute to their enhanced antioxidant properties. Ten distinct compounds were isolated and recognized in carnation flowers, with Isoorientin 2”-O-rhamnoside and Kurarinone demonstrating notable antioxidant activity and binding affinity to SOD1 and SOD3, as validated through antioxidant screening and molecular docking.ConclusionOverall, the findings from this study have expanded our knowledge of the phytochemical composition across different anatomical regions of the carnation plant, providing valuable insights for its holistic utilization.

Deficit irrigation is a common strategy to reduce water use and improve the sustainability of cotton production. However, the effects of water deficits on crop productivity and quality are subject to genotype by management by environmental interactions. This study investigated effects of water deficits and frequency of irrigation on cotton performance grown in semi-arid region, Xinjiang, the main cotton-growing area in China. Two field trials (2020 and 2021) with split experimental design, including main factors of three irrigation levels (moderate-deficit, mild-deficit and full-irrigation) and split factors of three irrigation frequencies (4, 8 and 12 days) were conducted. Results from two trials both showed little negative influence of irrigation levels on yield, and higher irrigation frequency improved yield under same irrigation level. Significant effects of irrigation levels on yield components were found in 2021, with a 22 % increase in boll number and an 18 % reduction in boll weight under moderate-deficit irrigation compared with those under full-irrigation. Interactions between irrigation levels and frequencies significantly affected harvest index (HI), showing that reduced irrigation might be beneficial for improving HI. However, decreased fibre length while increased fibre micronaire were found under deficit irrigation. A strong association between radiation use efficiency (RUE) and boll growth rate was observed, suggesting that RUE might be the driving force of yield formation. A tight correlation between both biomass and transpiration efficiency versus delta temperature between air and canopy (ΔTair-canopy) was observed, suggesting ΔTair-canopy could be used as an efficient tool to assess plant production under deficit irrigation. This study provided an improved understanding of the physiological basis of cotton yield formation and further identified a high-throughput and instantaneous method to monitor effects of deficit irrigation on crop productivity.

Abstract Background Meniere disease, characterized by intermittent episodes of vertigo, fluctuating sensorineural hearing loss, tinnitus, and aural pressure, is a common cause of vertigo in humans. The pathogenesis of Meniere disease remains unknown. The current study aimed to describe a novel pathological change discovered in the inner ears of patients with Meniere disease who underwent labyrinthectomy. Methods This retrospective case‐control study was conducted with 21 patients with MD who underwent labyrinthectomy. A total of 15 patients diagnosed with acoustic neuroma or glomus jugular tumor were review over the same period of time as control. The clinical information of the patients and the pathological features of the membrane are described. Results The new pathological tissue was a morbid membrane structure sealing the round window, characterized by the formation of lymphatic capillaries. Histochemical and immunofluorescent staining was positive for D2‐40, LYVE‐1, podoplanin, and PROX1, which are the classical markers of the lymphatic vessels. Transmission electron microscopy revealed that the lymph capillaries lacked a typical basement membrane and that their ends were blind, composed of a single layer of endothelial cells with valval connection structures between adjacent capillary epithelial cells. Conclusion This is the first report of lymphatic vessels in the human inner ear, and this pathological structure is a completely new discovery. The lymphatic vessels may develop due to inflammation or decompensation of pressure in the inner ear, suggesting that the inner ear can reactively form lymphatic vessels in some inflammation and fluid flow‐dependent pathological conditions. The current findings help in improving our understanding of the pathogenesis of Meniere disease.

Objective: To investigate the contribution of YWHAZ gene on the radioresistance and metastasis ability of oral squamous cell carcinoma (OSCC) cells. Methods: The relationship between the expression level of YWHAZ gene and the survival of head and neck squamous cell carcinoma (HNSC) patients was analyzed using Gene Expression Profiling Interactive Analysis (GEPIA) database. A radioresistance cell line (CAL-27R) was constructed by irradiating CAL-27 ​cells with fractional doses. Cell survival was measured by colony formation assay. Cell migration and invasion were detected by transwell assay. The formation of γH2AX foci was detected by immunofluorescence assay. The protein expressions were detected by Western blot assay. In some experiments, CAL-27R cells were effectively transferred with siRNA YWHAZ (siYWHAZ). Results: GEPIA database showed that the expression level of YWHAZ in HNSC tumors was higher than that in adjacent normal tissues, and the HNSC patients with higher level of YWHAZ had a shorter survival. In vitro experiments demonstrated that the expression of YWHAZ protein in CAL-27 ​cells was lower than HSC-3 ​cells (t ​= ​18.89, P ​

Abstract The radiator with heat transfer capability is able to guarantee the stable operation of hydro generator set, while the long-term and continuous scouring on radiator pipes by cooling medium will lead to thinning or even perforation of pipe wall, which triggers wall failure. This paper analyzes and predicts the failure mechanism of radiator’s pipe wall, and investigates the effects of water flow velocity, sand content and sand particle size on erosion damage of radiator pipe by establishing a test bench for pipe erosion. The results show that the increase of above parameters will lead to the increasing erosion rate, especially when the sand content is 1%, the velocity is 8 m/s and the sand particle size is 0.85 mm, the erosion damage will be particularly serious. Based on experimental data, BP and LSSVM models are employed to predict the pipe wall failure, and PSO algorithm is used to optimize the two models. The optimized PSO-BP has the highest accuracy with the mean absolute error (MAE) of 0.2070 and the mean absolute percentage error (MAPE) of 4.702%. The findings provide a reference for wall failure analysis of radiator, which is of great significance for unit's safe operation.

Abstract Over the years, the research of backward stochastic differential equations (BSDEs) has come a long way. As a extension of the BSDEs, the BSDEs with time delay have played a major role in the stochastic optimal control, financial risk, insurance management, pricing, and hedging. In this paper, we study a class of BSDEs with time-delay generators driven by Caputo fractional derivatives. In contrast to conventional BSDEs, in this class of equations, the generator is also affected by the past values of solutions. Under the Lipschitz condition and some new assumptions, we present a theorem on the existence and uniqueness of solutions.

12Cr13 martensitic stainless steel has been selected as the structural material for steam turbine blade which is frequently subjected to low-cycle fatigue (LCF) damage. The study involved conducting low-cycle fatigue (LCF) tests under strain control at various temperatures (25 °C, 250 °C, 350 °C, 450 °C) and strain amplitudes (±0.3 %, ±0.4 %, ±0.5 %, ±0.6 %). The cyclic deformation behavior, primarily indicating cyclic stress response and the Massing effect is thoroughly analyzed based on the characterization of dislocation microstructure and electron backscatter diffraction maps. The mechanism of crack initiation and the propagation behavior are discussed based on the SEM observations of microcracks on the specimen surface and the fracture surface morphology. The influence of temperature and strain amplitude on fatigue life behavior is determined, and the underlying mechanisms are revealed. Moreover, the life prediction is performed by using the classical Basquin-Coffin-Manson model at ambient temperature.

There is much controversy surrounding factors that affect the distribution of mangrove plants across the intertidal gradient. It was previously hypothesized that mangrove zonation was attributed to tidal sorting (TSH) of its propagules according to size (weight) or differential ability of propagules to establish in deep water. However, observational and experimental evidence have provided little support for the actual mechanism(s) of mangrove zonation. In general, species distribution pattern is the consequence of propagule dispersal. The specific gravity of water-borne mangrove propagules may affect their buoyancy, with inherent links to dispersal, thereby potentially influencing tree zonation. Propagule specific gravity can influence the distribution of mangroves in the context of global change, particularly in response to changes in seawater salinity. In this study, we measured the specific gravity and weight of 35 mangrove species propagules. There was no correlation between the weight of the propagule and its specific gravity. The specific gravity of propagules of true mangrove species was significantly greater than that of semi-mangrove. The results of the correlation between propagule specific gravity and the relative surface elevation of field distribution support the hypothesis that propagules are subject to tidal sorting and are not related to weight but to specific gravity. This newfound understanding of mangrove dispersal and distribution is critical in the context of mangrove protection and restoration, especially in projecting the effects of anthropogenic activities and global change on mangrove communities.

Abstract Determination of the key vertical level for cloud condensation nuclei concentration (CCNC) explosions has been a long‐term issue in CCN‐cloud interaction studies. An idealized hailstorm is simulated with 37 sensitivity runs, including an initial CCNC grouping vertically from the ground to the cloud top, increasing from 100 to 3,000 mg−1. The results reveal a key zone from 750 to 800 hPa near the median boundary layer, where an explosion of CCNC plays a dominant role in the nonmonotonic response of the hail precipitation rate. The explosion of CCNC in this zone could initially result in the condensation of more water vapor into the clouds, which could be transported to a greater vertical extent to significantly affect the riming collection efficiency. However, the dominant zone for the total precipitation rate is wider at heights of 700–800 hPa due to the lower sensitivity of the riming collection efficiency.

We point out a link between orbital angular momentum (OAM) carrying light beams and number theory. The established link makes it possible to formulate and implement a simple and ultrafast protocol for prime number factorization by employing OAM endowed beams that are modulated by a prime number sieve. We are able to differentiate factors from non-factors of a number by simply measuring the on-axis intensity of light in the rear focal plane of a thin lens focusing on a source beam. The proposed protocol solely relies on the periodicity of the OAM phase distribution, and hence, it is applicable to fully as well as partially coherent fields of any frequency and physical nature—from optical or x-ray to matter waves—endowed with OAM. Our experimental results are in excellent agreement with our theory. We anticipate that our protocol will trigger new developments in optical cryptography and information processing with OAM beams.

Objectives Little study has reported the association of maternal weight gain in early pregnancy with fetal congenital heart disease (CHD). We aimed to explore the potential relationship based on a China birth cohort while adjusting by multiple factors.Design Cohort study.Setting China birth cohort study conducted from 2017 to 2021.Participants The study finally included 114 672 singleton pregnancies in the 6–14 weeks of gestation, without missing data or outliers, loss to follow-up or abnormal conditions other than CHD. The proportion of CHD was 0.65% (749 cases).Primary and secondary outcome measures Association between maternal pre-pregnancy weight gain and CHD in the offspring were analysed by multivariate logistic regression, with the unadjusted, minimally adjusted and maximally adjusted methods, respectively.Results The first-trimester weight gain showed similar discrimination of fetal CHD to that period of maternal body mass index (BMI) change (DeLong tests: p=0.091). Compared with weight gain in the lowest quartile (the weight gain less than 0.0 kg), the highest quartile (over 2.0 kg) was associated with a higher risk of fetal CHD in unadjusted (OR 1.36, 95% CI: 1.08 to 1.72), minimally adjusted (adjusted OR (aOR) 1.29, 95% CI: 1.02 to 1.62) and maximally adjusted (aOR 1.29, 95% CI: 1.02 to 1.63) models. The association remains robust in pregnant women with morning sickness, normal pre-pregnancy BMI, moderate physical activity, college/university level, natural conception or with folic acid (FA) and/or multivitamin supplementation.Conclusions and relevance Although the association of maternal pre-pregnancy weight gain on fetal CHD is weak, the excessive weight gain may be a potential predictor of CHD in the offspring, especially in those with morning sickness and other conditions that are routine in the cohort, such as normal pre-pregnancy BMI, moderate physical activity, college/university level, natural conception or with FA and/or multivitamin supplementation.

Abstract Moving humans, agents, and subjects bring many challenges to robot self‐localisation and environment perception. To adapt to dynamic environments, SLAM researchers typically apply several deep learning image segmentation models to eliminate these moving obstacles. However, these moving obstacle segmentation methods cost too much computation resource for the onboard processing of mobile robots. In the current industrial environment, mobile robot collaboration scenario, the noise of mobile robots could be easily found by on‐board audio‐sensing processors and the direction of sound sources can be effectively acquired by sound source estimation algorithms, but the distance estimation of sound sources is difficult. However, in the field of visual perception, the 3D structure information of the scene is relatively easy to obtain, but the recognition and segmentation of moving objects is more difficult. To address these problems, a novel vision‐audio fusion method that combines sound source localisation methods with a visual SLAM scheme is proposed, thereby eliminating the effect of dynamic obstacles on multi‐agent systems. Several heterogeneous robots experiments in different dynamic scenes indicate very stable self‐localisation and environment reconstruction performance of our method.

In regions with limited resources and moderate incomes, the relentless spectre of cardiovascular diseases (CVDs) continues to loom large. Amidst this challenge, the precise classification of heart sounds is emerging as a pivotal linchpin in the realm of early CVD diagnosis and intervention. Manual heart sound auscultation efficacy remains tethered to the expertise of physicians, but the tides are shifting. With deep learning algorithms, heart sound classification reaches new heights. In this paradigm-shifting article, we unveil an ingenious model fortified by bispectrum-inspired feature extraction and the cutting-edge prowess of the Vision Transformer (ViT) model. This model spearheads the binary classification of heart sounds, labelling them as either 'normal' or 'abnormal.' Our model uses data from the PhysioNet Challenge 2022 database, which contains 3163 data points from 942 patients. The model showcases an adept classification process with a remarkable consistency, notably holding its own when distinguishing between heart sounds of pregnant and nonpregnant patients. Moreover, we dare to challenge the status quo. This article boldly pits the performance of our model against that of seasoned cardiologists. Our model emerges as the triumphant frontrunner, eclipsing the proficiency of even the most seasoned cardiologists. In a world where health resources are unevenly distributed, this pioneering work offers a beacon of hope, unlocking a future where advanced algorithms not only match but surpass human expertise. Step into the forefront of transformative cardiac care—where artificial intelligence becomes the key to unravelling the secrets of heart sounds.

Objective To establish a blood transfusion adverse event management system and apply it to adverse events management, so as to enhance the ability to identify and process reports as well as prevent adverse events. Methods According to the errors during the whole process of blood transfusion, the management information system of blood transfusion adverse events was established, and the data of adverse transfusion reactions and adverse transfusion events from 2020 to 2022 were collected according to the system requirements. The system monitoring data and statistical analysis were used to analyze the causes of errors in each link of blood transfusion, sort the incidence of each department, focus on supervising the departments with high frequency of adverse events, and propose effective rectification. Results The management system counted 51 cases of adverse reactions. The incidence of adverse reactions of plasma (43.1 %, 22/51) was higher than that of red blood cells (39.2 %, 20/51), and the number of allergic reactions was slightly higher than that of febrile non-hemolytic transfusion reaction. Among the 628 cases of adverse transfusion events, blood transport, inbound and storage (TS-A) errors accounted for the highest proportion of 46.2% (290/628), 20.9% (131/628) in post-transfusion disposal and evaluation (TS-G) and 15.8% (99/628) in pre-transfusion evaluation and transfusion application (TS-B). TS-A12 accounted for 63.8 % (185/290) in TS-A errors, which was mainly due to plasma leakage caused by extrusion during transport and the expiration of red blood cells caused by insufficient blood inventory management. TS-B errors mainly focus on the failure to fully assess the bleeding tendency of patients before surgical system surgery, resulting in no or insufficient preoperative blood preparation. Most of the TS-G errors were unqualified medical record. Conclusion Blood transfusion adverse event management system can help to identify and prevent the occurrence or recurrence of adverse events, formulate targeted rectification and preventive measures, and improve the haemovigilance ability.

Abstract The pandemic of COVID-19 was a major public health events and had a deeply impact on the healthcare acquired by patients with inflammatory bowel disease (IBD). The purpose of this study was to evaluate the long-term impacts on healthcare service in Chinese IBD patients under the dynamic zero-COVID strategy. The study was performed in the Inflammatory Bowel Disease Quality of Care Centers in mainland China in 2021. The data about the healthcare was collected by a 44-item questionnaire. Totally 463 were from ulcerative colitis (UC) patients and 538 from Crohn’s disease (CD) patients were included in the study. The pandemic impacted 37.5% patients on their treatment, and the biggest problem was unable to follow up timely (77.9%). There was a significant increase in healthcare costs in CD (P

Abstract Climate change poses a significant threat to agriculture. However, climatic trends and their impact on Mississippi (MS) maize (Zea mays L.) are unknown. The objectives were to: (i) analyze trends in climatic variables (1970 to 2020) using Mann–Kendall and Sen slope method, (ii) quantify the impact of climate change on maize yield in short and long run using the auto-regressive distributive lag (ARDL) model, and (iii) categorize the critical months for maize-climate link using Pearson’s correlation matrix. The climatic variables considered were maximum temperature (Tmax), minimum temperature (Tmin), diurnal temperature range (DTR), precipitation (PT), relative humidity (RH), and carbon emissions (CO2). The pre-analysis, post-analysis, and model robustness statistical tests were verified, and all conditions were met. A significant upward trend in Tmax (0.13 °C/decade), Tmin (0.27 °C/decade), and CO2 (5.1 units/decade), and a downward trend in DTR ( − 0.15 °C/decade) were noted. The PT and RH insignificantly increased by 4.32 mm and 0.11% per decade, respectively. The ARDL model explained 76.6% of the total variations in maize yield. Notably, the maize yield had a negative correlation with Tmax for June, and July, with PT in August, and with DTR for June, July, and August, whereas a positive correlation was noted with Tmin in June, July, and August. Overall, a unit change in Tmax reduced the maize yield by 7.39% and 26.33%, and a unit change in PT reduced it by 0.65% and 2.69% in the short and long run, respectively. However, a unit change in Tmin, and CO2 emissions increased maize yield by 20.68% and 0.63% in the long run with no short run effect. Overall, it is imperative to reassess the agronomic management strategies, developing and testing cultivars adaptable to the revealed climatic trend, with ability to withstand severe weather conditions in ensuring sustainable maize production.

The rapid development of generative technologies has made the production of forged products easier, and AI-generated forged images are increasingly difficult to accurately detect, posing serious privacy risks and cognitive obstacles to individuals and society. Therefore, constructing an effective method that can accurately detect and locate forged regions has become an important task. This paper proposes a hierarchical and progressive forged image detection and localization method called HPUNet. This method assigns more reasonable hierarchical multi-level labels to the dataset as supervisory information at different levels, following cognitive laws. Secondly, multiple types of features are extracted from AI-generated images for detection and localization, and the detection and localization results are combined to enhance the task-relevant features. Subsequently, HPUNet expands the obtained image features into four different resolutions and performs detection and localization at different levels in a coarse-to-fine cognitive order. To address the limited feature field of view caused by inconsistent forgery sizes, we employ three sets of densely cross-connected hierarchical networks for sufficient interaction between feature images at different resolutions. Finally, a UNet network with a soft-threshold-constrained feature enhancement module is used to achieve detection and localization at different scales, and the reliance on a progressive mechanism establishes relationships between different branches. We use ACC and F1 as evaluation metrics, and extensive experiments on our method and the baseline methods demonstrate the effectiveness of our approach.

Agarwood is a highly sought-after resinous wood for use in medicine, incense, and perfume production. However, the process of agarwood formation is slow. In this study, the induction of agarwood formation in three-year-old Aquilaria sinensis “Qinan” trees through treatment with ethephon, hydrogen peroxide, sodium chloride, distilled water, and wounding was investigated. The results showed that the starch content significantly decreased and that the soluble sugar content significantly increased during the process of agarwood formation, with no significant difference between the different treatment groups. The net photosynthetic rate significantly decreased. Except for the sodium chloride treatment, the total antioxidant capacity and the contents of flavonoids and phenols significantly increased during the process of agarwood formation. The essential oil yield of the ethephon and hydrogen peroxide treatment groups was significantly higher than that of the other treatment groups, with the highest essential oil yield in the ethephon treatment group. Compared to the control group, salt treatment produced the lowest essential oil yield of agarwood. The results indicate that appropriate concentrations of ethephon and hydrogen peroxide can promote the formation of agarwood in A. sinensis “Qinan”.

The tomato (Solanum lycopersicum L.), a widely cultivated and economically important vegetable crop, is subject to a number of biotic and abiotic stresses in nature. Several abiotic and biotic stresses have been demonstrated to elevate the concentration of cytosolic free Ca2+ ([Ca2+]i) in Arabidopsis due to the influx of calcium ions. In this study, recombinant aequorin was introduced into the tomato in order to investigate the change in [Ca2+]i when treated with exogenous Ca2+. This resulted in strong luminescence signals, which were mainly observed in the roots. Luminescence signals were also detected in the whole plant, including the leaves, when a surfactant (Silwet L-77) was added to coelenterazine. The concentration of [Ca2+]i increased with the dosage of NaCl/elf18. The luminescence signals also showed a lower increase in intensity with elf18 treatment compared to NaCl treatment. Furthermore, the [Ca2+]i responses to other abiotic or biotic stresses, such as H2O2 and Pep1, were also evaluated. It was found that this transgenic tomato expressing aequorin can effectively detect changes in [Ca2+]i levels. The transgenic tomato expressing aequorin represents an effective tool for detecting changes in [Ca2+]i and provides a solid basis for investigating the adaptation mechanisms of tomatoes to various abiotic and biotic stresses. Moreover, the aequorin-based system would be a highly valuable tool for studying the specificity and crosstalk of plant signalling networks under abiotic and biotic stresses in tomatoes.

Flowering in plants is pivotal for initiating and advancing reproductive processes, impacting regional adaptation and crop yield. Despite numerous cloned and identified flowering time genes, research in cotton remains sparse. This study identified GhSWEET42 as a key determinant of the flowering time in cotton, demonstrating that its heterologous expression in Arabidopsis accelerated flowering under LD conditions compared to WT. Transgenic plants exhibited upregulated expression of the flowering inducers AtFT, AtSOC1, AtGI, and AtFKF1, alongside downregulated expression of the repressors AtTSF, AtFLC, and AtRGL2, correlating with the earlier flowering phenotype. GhSWEET42 showed a constitutive expression pattern, with elevated levels in the leaves, petals, and flower buds, and was notably higher in early-maturing cotton varieties. Subcellular localization assays confirmed GhSWEET42’s presence on the cell membrane. Transcriptome analysis between WT and GhSWEET42-overexpressing Arabidopsis plants revealed 2393 differentially expressed genes (DEGs), spanning 221 biological processes, 93 molecular functions, and 37 cellular components according to Gene Ontology (GO) enrichment analysis. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis categorized the DEGs into metabolism and environmental information processing. These findings enhance the understanding of GhSWEET42’s function and provide a foundation for elucidating the molecular mechanisms governing flowering time regulation in cotton.

Salt marsh plants play a vital role in mediating nitrogen (N) biogeochemical cycle in estuarine and coastal ecosystems. However, the effects of invasive Spartina alterniflora on N fixation and removal, as well as how these two processes balance to determine the N budget, remain unclear. Here, simultaneous quantifications of N fixation and removal via 15N tracing experiment with native Phragmites australis, invasive S. alterniflora, and bare flats as well as corresponding functional gene abundance by qPCR were carried out to explore the response of N dynamics to S. alterniflora invasion. Our results showed that N fixation and removal rates ranged from 0.77 ± 0.08 to 16.12 ± 1.13 nmol/(g·h) and from 1.42 ± 0.14 to 16.35 ± 1.10 nmol/(g·h), respectively, and invasive S. alterniflora generally facilitated the two processes rates. Based on the difference between N removal and fixation rates, net N2 fluxes were estimated in the range of −0.39 ± 0.14 to 8.24 ± 2.23 nmol/(g·h). Estimated net N2 fluxes in S. alterniflora stands were lower than those in bare flats and P. australis stands, indicating that the increase in N removal caused by S. alterniflora invasion may be more than offset by N fixation process. Random forest analysis revealed that functional microorganisms were the most important factor associated with the corresponding N transformation process. Overall, our results highlight the importance of N fixation in evaluating N budget of estuarine and coastal wetlands, providing valuable insights into the ecological effect of S. alterniflora invasion.

Abstract Human epidermal growth factor receptor 2 (HER2) is a protein that is overexpressed in some types of cancer, including breast and urothelial cancer. Here we found that HER2 was present in a portion of colon cancer patients, raising the possibility of using anti-HER2 therapy. RC48, a novel antibody-drug conjugate (ADC) comprising cytotoxic monomethyl auristatin E (MMAE) and an anti-HER2 antibody tethered via a linker, showed a comparable therapeutic effect in both HER2 low expressed (IHC2+/FISH- or IHC+) and high expressed urothelial cancer patients. In vitro studies using colon cancer cell lines showed that RC48 effectively impeded the proliferation of HER2-positive cells, indicating its potential as a treatment for HER2-positive colon cancer. Mechanism study showed that RC48 not only induces cell cycle arrest but also disrupts HER2-mediated restain of cGAS-STING signaling, potentially activating an immune response against the cancer cells. The administration of RC48 significantly reduced the growth of HER2-positive colon cancer and made HER2-positive colon cancer cells more susceptible to immunotherapy. The results of our study will contribute to determining the feasibility of RC48 as a therapeutic option for HER2-positive colon cancer.

Abstract Skeletal muscle and thermogenic adipose tissue are both critical for the maintenance of body temperature in mammals. However, whether these two tissues are interconnected to modulate thermogenesis and metabolic homeostasis in response to thermal stress remains inconclusive. Here, we report that human and mouse obesity is associated with elevated Musclin levels in both muscle and circulation. Intriguingly, muscle expression of Musclin is markedly increased or decreased when the male mice are housed in thermoneutral or chronic cool conditions, respectively. Beige fat is then identified as the primary site of Musclin action. Muscle-transgenic or AAV-mediated overexpression of Musclin attenuates beige fat thermogenesis, thereby exacerbating diet-induced obesity and metabolic disorders in male mice. Conversely, Musclin inactivation by muscle-specific ablation or neutralizing antibody treatment promotes beige fat thermogenesis and improves metabolic homeostasis in male mice. Mechanistically, Musclin binds to transferrin receptor 1 (Tfr1) and antagonizes Tfr1-mediated cAMP/PKA-dependent thermogenic induction in beige adipocytes. This work defines the temperature-sensitive myokine Musclin as a negative regulator of adipose thermogenesis that exacerbates the deterioration of metabolic health in obese male mice and thus provides a framework for the therapeutic targeting of this endocrine pathway.

Objectives: Present study aims to explore the surgery patterns and survival of T4N2 non-small cell lung cancer (NSCLC) in real-world condition. Materials and methods: Clinical stage T4N2 NSCLC patients in Surveillance, Epidemiology and End Result Program were extracted. Cox regression was used for calculation of hazard ratio (HR) and confidence interval (CI), and landmark analysis was used for survival test at different cut-off time points. Results: There were 1445 eligible patients included, of which 306 patients received surgery alone, 390 patients received induction therapy, and 749 patients received adjuvant therapy. For resection types, 1210 patients received lobectomy and 235 received pneumonectomy. Among patient receiving induction therapy, the overall survival (OS) HRs of pneumonectomy at 1-year, 3-year, 5-year, and 8-year cut-off points were 1.330, 0.972, 1.231, and 1.332 (P ​= ​0.708, 0.972, 0.281 and 0.145), respectively, and cancer-specific survival (CSS) HRs at these landmark points were 2.386, 1.231, 1.455, and 1.480 (P ​= ​0.293, P ​= ​0.409, 0.059 and 0.056), respectively. Among patients receiving adjuvant therapy, the OS HRs of pneumonectomy at 1-year and 8-year cut-off points were 1.570 and 1.274 (P ​= ​0.050 and 0.087), respectively, and CSS HRs at these landmark points were 1.493 and 1.284 (P ​= ​0.096 and 0.094), respectively. Both OS and CSS of patients receiving lobectomy were superior than pneumonectomy at 3-year and 5-year in this cohort. For patients receiving surgery alone, pneumonectomy resulted in inferior survival than lobectomy at all cut-off points (all P ​

Recently, some new Qi-Nan clones of Aquilaria sinensis (Lour.) Spreng which intensively produces high-quality agarwood have been identified and propagated through grafting techniques. Previous studies have primarily focused on ordinary A. sinensis and the differences in composition when compared to Qi-Nan and ordinary A. sinensis. There are few studies on the formation mechanism of Qi-Nan agarwood and the dynamic changes in components and endophytic fungi during the induction process. In this paper, the characteristics, chemical composition, and changes in endophytic fungi of Qi-Nan agarwood induced after 1 year, 2 years, and 3 years were studied, and Qi-Nan white wood was used as the control. The results showed that the yield of Qi-Nan agarwood continued to increase with the induction time over a period of 3 years, while the content of alcohol extract from Qi-Nan agarwood reached its peak at two years. During the formation of agarwood, starch and soluble sugars in xylem rays and interxylary phloem are consumed and reduced. Most of the oily substances in agarwood were filled in xylem ray cells and interxylary phloem, and a small amount was filled in xylem vessels. The main components of Qi-Nan agarwood are also chromones and sesquiterpenes. With an increasing induction time, the content of sesquiterpenes increased, while the content of chromones decreased. The most abundant chromones in Qi-Nan agarwood were 2-(2-Phenethyl) chromone, 2-[2-(3-Methoxy-4-hydroxyphenyl) ethyl] chromone, and2-[2-(4-Methoxyphenyl) ethyl] chromone. Significant differences were observed in the species of the endophytic fungi found in Qi-Nan agarwood at different induction times. A total of 4 phyla, 73 orders, and 448 genera were found in Qi-Nan agarwood dominated by Ascomycota and Basidiomycota. Different induction times had a significant effect on the diversity of the endophytic fungal community in Qi-Nan. After the induction of agarwood formation, the diversity of Qi-Nan endophytic fungi decreased. Correlation analysis showed that there was a significant positive correlation between endophytic fungi and the yield, alcohol extract content, sesquiterpene content, and chromone content of Qi-Nan agarwood, which indicated that endophytic fungi play a role in promoting the formation of Qi-Nan agarwood. Qi-Nan agarwood produced at different induction times exhibited strong antioxidant capacity. DPPH free radical scavenging activity and reactive oxygen species clearance activity were significantly positively correlated with the content of sesquiterpenes and chromones in Qi-Nan agarwood.

ABSTRACT: Previous work has shown that dietary treatments affect woody breast (WB) incidence differently, which indicates that gut conditions such as gut barrier function, inflammation, and oxidative stress are likely related to WB. In this study, dietary supplementation with antibiotics (bacitracin) or probiotics (Bacillus subtilis) was investigated for their effects on the expression of transcripts related to gut barrier function, inflammation, and oxidative stress in the mucus lining of the jejunum from broilers with or without WB. A split-plot experimental design was used in this study. The dietary treatments served as the main plot factor and the breast muscle condition was the subplot factor. On d 41, jejunum mucus was collected from 1 bird from each of 3 replicate pens in each 3 dietary treatment groups that exhibited WB and an additional bird that contained a normal breast (3 biological replicates/treatment/phenotype; 3 × 3 × 2, total N = 18). Total RNA was extracted using a commercial RNA extraction kit. The expression levels of CLDN1, MUC6, TLR2A, TLR2B, TLR4, IFN-γ, IL-1β, IL-8L1, IL-10, NOS2, and SOD were determined using 2-step RT-qPCR analysis. The gene expression difference in ΔCt values was determined after normalizing with the chicken 18S rRNA gene. When the significant differences occurred between treatments, the relative fold change was calculated using the ΔΔCt method and the significance level was calculated. The PROC GLM procedure of SAS 9.4 was used, and the level of significance was set at P ≤ 0.05. There were no significant interactive effects between diet and the breast muscle condition on the expression of any of the genes tested. However, birds with WB exhibited higher MUC6 (P < 0.0001) gene expression levels than birds with normal breast muscles. In addition, the expression of SOD decreased in birds that were fed the antibiotic diet when compared to birds that were fed the probiotic diet (P = 0.014). In conclusion, WB identified in broilers tested in the current study is attributed to increased expression of mucin, indicating a correlation between WB incidence and gel-forming mucin secretion and pathogen signaling.

Strong turbulence is generated by the blending of opposed staggered jets (OSJs). This turbulence results in fluid mixing and energy dissipation, which are crucial for pollutant dilution and the filling of navigation lock chambers. A renormalization group k-ε turbulence model is adopted to conduct three-dimensional simulations of OSJs at various stagger distances. The blending characteristics of two square water jets at eight stagger distances L* within a finite field are examined; here, L* is defined as the distance between the center lines of the staggered jets divided by the jet diameter. The initial Reynolds number and inlet diameter of the jets for the numerical simulations are set to 2.99 × 106 and 0.6 m, respectively. The numerical results show that there is a linear correlation between the decay exponent and the jet half-width, both of which increase and then gradually stabilize with increasing L*. Intriguingly, the vortex strength and blending length both increase at first before decreasing as L* increases, and the blending effectiveness distribution mirrors these fluctuations. Moreover, a decay model for the axial velocity is formulated in terms of the decay exponent and L*. These investigations yield substantial theoretical results underpinning fluid mixing and orifice arrangement in navigation lock chambers.

Summary:. Leg muscle hypertrophy is a unique physical symptom in East Asian women. Compared with traditional surgical treatment for calf muscle hypertrophy, botulinum toxin is widely favored by East Asian women because of its minimal trauma and significant effects. We describe the case of a 22-year-old woman with pulmonary embolism because of deep vein thrombosis, who presented with hypertrophy of bilateral calf muscles, and was administered 300 U of botulinum toxin A injection in July 2022. On the third day after the injection, she experienced swelling and pain in her left leg, which gradually worsened and made walking difficult. She underwent an ultrasound examination of lower limbs, which revealed several deep and shallow vein thrombi in the left lower limb. Computed tomography arterial imaging indicated multiple embolisms in pulmonary arteries. This study aimed to explore and analyze the causes of pulmonary embolism after botulinum toxin treatment for calf muscle hypertrophy by reviewing and analyzing the patient’s symptoms, diagnosis, and treatment process to provide management strategies for treatment and prevention of this disease.

Problem: Chest radiography is a crucial tool for diagnosing thoracic disorders, but interpretation errors and a lack of qualified practitioners can cause delays in treatment. Aim: This study aimed to develop a reliable multi-classification artificial intelligence (AI) tool to improve the accuracy and efficiency of chest radiograph diagnosis. Methods: We developed a convolutional neural network (CNN) capable of distinguishing among 26 thoracic diagnoses. The model was trained and externally validated using 795,055 chest radiographs from 13 datasets across 4 countries. Results: The CNN model achieved an average area under the curve (AUC) of 0.961 across all 26 diagnoses in the testing set. COVID-19 detection achieved perfect accuracy (AUC 1.000, [95% confidence interval {CI}, 1.000 to 1.000]), while effusion or pleural effusion detection showed the lowest accuracy (AUC 0.8453, [95% CI, 0.8417 to 0.8489]). In external validation, the model demonstrated strong reproducibility and generalizability within the local dataset, achieving an AUC of 0.9634 for lung opacity detection (95% CI, 0.9423 to 0.9702). The CNN outperformed both radiologists and nonradiological physicians, particularly in trans-device image recognition. Even for diseases not specifically trained on, such as aortic dissection, the AI model showed considerable scalability and enhanced diagnostic accuracy for physicians of varying experience levels (all P < 0.05). Additionally, our model exhibited no gender bias (P > 0.05). Conclusion: The developed AI algorithm, now available as professional web-based software, substantively improves chest radiograph interpretation. This research advances medical imaging and offers substantial diagnostic support in clinical settings.

As the weakest link in the shield segment, the reinforcement and repair technology of shield segment joint has received widespread attention. In this study, an finite element model utilizing a cohesive zone model (CZM) was constructed to simulate the mechanical behavior of the shield segment joint during the whole fracture process. The proposed modeling method of joint allows multiple layers of steel bars to be stacked without interference by applying cohesive elements. Cohesive elements were employed to represent the mechanical response of potential fracture surfaces in concrete, as well as the interfaces between steel–concrete and fiber-reinforced polymer (FRP)–concrete, by utilizing various constitutive models tailored for mixed-mode loading conditions. A group of experiments was chosen to assess the precision of the proposed model by comparing the mechanical response and the fracture patterns. Finally, parameter analyses were conducted to study the reinforcement effect of the FRP bonding length and width on the shield segment joint. The results indicate that external bonding of FRP can effectively enhance the bearing capacity and stiffness of shield segment joints. However, insufficient bonding length or width may significantly reduce the strengthening effect and potentially decrease the ductility of the joint.

Background: Rising rates of lung cancer screening have contributed to an increase in pulmonary nodule diagnosis rates. Studies have shown that psychosocial factors and hormones have an impact on the development of the oncological diseases. Therefore, we conducted this study to explore the potential relationship between pulmonary nodules pathology and patient personality traits and hormone levels. Methods: This study enrolled 245 individuals who had first been diagnosed with pulmonary nodules in Tangdu Hospital and admitted for surgery. The personality profile of these patients was analyzed on admission using the C-Type Behavioral Scale and hormone levels were measured in preoperative serum samples. Associations between nodule pathology, personality scores, and hormone levels， were then assessed through Statistical methods analysis. Results: Behavioral scale analyses revealed significant differences four items, including depression, anger outward, optimism, and social support (P