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Abstract The objective of this research was to explore the potential association between lipid accumulation product (LAP) and chronic kidney disease (CKD) among adult population of United States (US). Using cross-sectional data from the 2013 to 2018 National Health and Nutrition Examination Survey (NHANES), we explored the association of LAP with CKD, low estimated glomerular filtration rate (eGFR), and albuminuria. This analysis encompassed multivariate logistic regression analyses, smoothed curve fitting, subgroup analyses, and interaction tests. We found a significant positive association between higher ln-transformed LAP (LAP was transformed using a natural logarithm) and the prevalence of CKD, low-eGFR and albuminuria. Notably, this association of ln-transformed LAP with CKD and albuminuria was significantly influenced by diabetes status and sex (P for interaction 0.05). Additionally, in model 3 (adjusted for all included covariates except eGFR and urinary albumin-creatinine ratio (UACR)), a nonlinear relationship was identified between ln-transformed LAP and the presence of both CKD and albuminuria, with inflection points of 4.57 and 4.49, respectively. This indicates that this correlation is more pronounced on the right of the inflection point. In conclusion, the findings indicate a significant association between LAP and the prevalence of CKD in US adults.

Abstract As per the regulations of Intergovernmental Panel on Climate Change (IPCC), the country’s carbon emission data hold primacy. Nevertheless, establishing and utilizing a database pose a daunting challenge. This study presents the “Carbon Seer System,” a novel software prototype designed to inform and educate users about the carbon footprint during their production and in daily life. The development process involved a three-stage user interview process, ensuring system’s alignment with user needs and preferences. The system employs machine learning and visual recognition technology, including convolutional neural networks (CNNs), feature pyramid networks, and self-attention mechanisms, enabling users to analyze captured images for carbon emission factors. It automatically identifies the carbon emission factors of industrial products, energy producers, household producers, waste treatment, and transportation. A unique “group detection” method allows for the simultaneous analysis of multiple objects in a single image, enhancing user convenience. Additionally, the software features a carbon footprint tracker and a carbon sink dashboard, providing users with insights into their carbon emissions and the efforts needed for offsetting. The study concludes that the “Carbon Seer System” represents a significant step towards individual enablement at understanding and actively participating in a low-carbon lifestyle.

Abstract Purpose Bone metastases occur in 50-70% of patients with breast cancer (BC) and result in high mortality. Platelet distribution width (PDW), a commonly used parameter of activated platelets, has been associated with a poor prognosis in BC. We aim to investigate the prognostic role of PDW for bone metastasis in BC patients. Methods 515 patients who received BC surgery in the Harbin Medical University Cancer Hospital from July 1, 2016, to December 31, 2017, were reviewed. Patients’ characteristics and platelet indices upon enrollment in this study were collected. The Kaplan-Meier method was used to estimate the 5-year bone metastasis incidence. The univariate and multivariate Cox regression analyses were utilized to identify risk factors associated with bone metastasis. Results The patients with bone metastases exhibited lower PDW levels than the patients without bone metastases. Moreover, decreased PDW was significantly correlated with histologic type, multifocal disease, and lymph node status. In addition, the patients with reduced PDW levels were more likely to develop bone metastasis. Multivariate analysis showed that PDW was an independent predictor for bone metastasis. Conclusion PDW is an independent predictor of bone metastasis in BC. Further research is warranted.

The sea level in coastal areas of China reached the second highest in 2021, just after that recorded in 2022. External force and dynamic analyses based on tide gauges, satellite observations, reanalysis data and regional numerical outputs were conducted to understand these abnormally high sea levels and determine their possible causes. Results show that the coastal sea level of China had increased at an annual rate of 3.4 ± 0.3 mm during 1980–2021, with an acceleration of 0.06 ± 0.02 mm per year2. The superposition of significant oscillations of quasi-2, 3–7, quasi-9, quasi-11, quasi-19 and 20–30 years contributed to the anomalously high sea levels. The negative-phased El Niño/Southern Oscillation was correlated with the anomalously high sea level and the north‒south anti-phase pattern of the coastal sea level in 2021. Meanwhile, phase lags of 1–4 months occurred with the sea-level response. On a decadal timescale, the Pacific Decadal Oscillation (PDO) was negatively correlated with the anomalous mean sea level (MSL), and the negative-phased PDO contributed to the anomalous sea-level change in 2021. Particularly, the monthly MSL peaked in April and July, and the contribution of wind stress to the anomalously high sea level was 38.5% in the south of the Taiwan Strait in April and 30% along the coast of China in July. These results were consistent with the tide gauge and satellite data. Close agreement was also observed between the coastal sea-level fingerprint and the air and sea surface temperatures.

The coastal areas of the lower reaches of Oujiang River Basin are rich in groundwater resources. However, the unsustainable exploitation and utilization of groundwater have led to significant changes in the groundwater environment. Understanding the characteristics and genesis of groundwater salinization is crucial for preventing its deterioration and ensuring sustainable utilization. In this study, a comprehensive approach combining the ion ratio method, mineral saturation index method and multivariate statistical analysis was employed to investigate the hydrochemical characteristics and main controlling factors in the study area. The findings reveal that: (1) Groundwater samples in study area exhibit a neutral to slightly alkaline pH. The predominant chemical types of unconfined water are HCO3-Ca·Na, HCO3·Cl-Na·Ca and HCO3·SO4-Ca·Na, while confined water mainly exhibits Cl·HCO3-Na and Cl-Na types. (2) Salinity coefficients indicate an increase in salinity from unconfined to confined water. TDS, Na+ and Cl– concentrations show an increasing trend from mountainous to coastal areas in unconfined water, while confined water displays variability in TDS, Na+ and Cl– concentrations. (3) Groundwater salinity is mainly influenced by water-rock interactions, including the dissolution of halite and gypsum, cation exchange, and seawater intrusion etc. Additionally, human activities and carbonate dissolution contribute to salinity in unconfined water. Seawater intrusion is identified as the primary factor leading to higher salinity in confined water compared to unconfined water, with increasing cation exchange and seawater interaction observed from unconfined to confined water.

Musical training has long been viewed as a model for experience-dependent brain plasticity. Reports of musical training-induced brain plasticity are largely based on cross-sectional studies comparing musicians to non-musicians, which cannot address whether musical training itself is sufficient to induce these neurobiological changes or whether pre-existing neuroarchitecture before training predisposes children to succeed in music. Here, in a longitudinal investigation of children from infancy to school age (n = 25), we find brain structure in infancy that predicts subsequent music aptitude skills at school-age. Building on prior evidence implicating white matter organization of the corticospinal tract as a neural predisposition for musical training in adults, here we find that structural organization of the right corticospinal tract "in infancy" is associated with school-age tonal and rhythmic musical aptitude skills. Moreover, within the corpus callosum, an inter-hemispheric white matter pathway traditionally linked with musical training, we find that structural organization of this pathway in infancy is associated with subsequent tonal music aptitude. Our findings suggest predispositions prior to the onset of musical training from as early as infancy may serve as a scaffold upon which ongoing musical experience can build.

This article investigates the perspectives of international students in the United States who use writing centers to support their identities and to meet their writing needs and goals. Using survey and focus group data to look closely at how students use one writing center's online Profile and more broadly at the accessibility and responsiveness of writing center services, this study found that students have much to say about their place within writing centers and how writing consultants can best support them. Listening to these international student voices reveals how writing centers and other student support services must take the initiative in opening up conversations with and among our students to create the conditions for their success.

Objective: To assess the feasibility of using non-mydriatic fundus photography in conjunction with an artificial intelligence (AI) reading platform for large-scale screening of diabetic retinopathy (DR). Methods: In this study, we selected 120 patients with diabetes hospitalized in our institution from December 2019 to April 2021. Retinal imaging of 240 eyes was obtained using non-mydriatic fundus photography. The fundus images of these patients were divided into two groups based on different interpretation methods. In Experiment Group 1, the images were analyzed and graded for DR diagnosis using an AI reading platform. In Experiment Group 2, the images were analyzed and graded for DR diagnosis by an associate chief physician in ophthalmology, specializing in fundus diseases. Concurrently, all patients underwent the gold standard for DR diagnosis and grading—fundus fluorescein angiography (FFA)—with the outcomes serving as the Control Group. The diagnostic value of the two methods was assessed by comparing the results of Experiment Groups 1 and 2 with those of the Control Group. Results: Keeping the control group (FFA results) as the gold standard, no significant differences were observed between the two experimental groups regarding diagnostic sensitivity, specificity, false positive rate, false negative rate, positive predictive value, negative predictive value, Youden's index, Kappa value, and diagnostic accuracy (X2 = 0.371, P > 0.05). Conclusion: Compared with the manual reading group, the AI reading group revealed no significant differences across all diagnostic indicators, exhibiting high sensitivity and specificity, as well as a relatively high positive predictive value. Additionally, it demonstrated a high level of diagnostic consistency with the gold standard. This technology holds potential for suitability in large-scale screening of DR.

Abstract Discovering new treatments for melanoma will benefit human health. The mechanism by which deoxyhypusine synthase (DHPS) promotes melanoma development remains elucidated. Multi‐omics studies have revealed that DHPS regulates m6A modification and maintains mRNA stability in melanoma cells. Mechanistically, DHPS activates the hypusination of eukaryotic translation initiation factor 5A (eIF5A) to assist METTL3 localizing on its mRNA for m6A modification, then promoting METTL3 expression. Structure‐based design, synthesis, and activity screening yielded the hit compound GL‐1 as a DHPS inhibitor. Notably, GL‐1 directly inhibits DHPS binding to eIF5A, whereas GC‐7 cannot. Based on the clarification of the mode of action of GL‐1 on DHPS, it is found that GL‐1 can promote the accumulation of intracellular Cu2+ to induce apoptosis, and antibody microarray analysis shows that GL‐1 inhibits the expression of several cytokines. GL‐1 shows promising antitumor activity with good bioavailability in a xenograft tumor model. These findings clarify the molecular mechanisms by which DHPS regulates melanoma proliferation and demonstrate the potential of GL‐1 for clinical melanoma therapy.

BackgroundBone cement leakage (BCL) is one of the most prevalent complications of percutaneous kyphoplasty (PKP) for treating osteoporotic vertebral compression fracture (OVCF), which may result in severe secondary complications and poor outcomes. Previous studies employed several traditional machine learning (ML) models to predict BCL preoperatively, but effective and intelligent methods to bridge the distance between current models and real-life clinical applications remain lacking.MethodsWe will develop a deep learning (DL)-based prediction model that directly analyzes preoperative computed tomography (CT) and magnetic resonance imaging (MRI) of patients with OVCF to accurately predict BCL occurrence and classification during PKP. This retrospective study includes a retrospective internal dataset for DL model training and validation, a prospective internal dataset, and a cross-center external dataset for model testing. We will evaluate not only model’s predictive performance, but also its reliability by calculating its consistency with reference standards and comparing it with that of clinician prediction.DiscussionThe model holds an imperative clinical significance. Clinicians can formulate more targeted treatment strategies to minimize the incidence of BCL, thereby improving clinical outcomes by preoperatively identifying patients at high risk for each BCL subtype. In particular, the model holds great potential to be extended and applied in remote areas where medical resources are relatively scarce so that more patients can benefit from quality perioperative evaluation and management strategies. Moreover, the model will efficiently promote information sharing and decision-making between clinicians and patients, thereby increasing the overall quality of healthcare services.

Objective: This study aimed to analyze the FAERS database to identify adverse event associated with sunitinib to offer valuable insights for the judicious utilization of medication in clinical settings. Methods: Various disproportionality analysis techniques, such as the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPN), and multi-gamma Poisson shrinkage (MGPS), were employed to analyze adverse drug reaction (ADR) reports pertaining to sunitinib in the FAERS database from its market introduction up to the first quarter of 2023. Subsequently, a secondary screening process was conducted to identify reliable positive signals. Results: The analysis of sunitinib adverse event signals at the system-organ classification level encompassed 27 organ systems, with gastrointestinal and endocrine disorders emerging as the predominant SOCs. A total of 237 significant adverse events meeting all four algorithms were detected. Notably, this study revealed previously unreported adverse events, including pleural effusion and ascites, while potential adrenal toxicity-related adverse events, highlighted in the drug's specification, were not identified in this analysis. The study examined the relationship between the duration of sunitinib dosing and the onset of adverse events, revealing a median onset of 48 days (IQR, 15–160 days). The findings indicated that a majority of adverse events manifested early in the dosing period, with tumor progression, disease progression, and mortality becoming more prevalent after one year of treatment. Conclusion: In the clinical utilization of sunitinib, vigilant monitoring of potential adverse reactions is imperative during the initial phase of drug administration. In addition to the documented adverse reactions outlined in the drug specification, healthcare providers should remain attentive to potential adverse reactions such as pleural effusion, ascites, and tumor development.

The cell wall serves as the primary barrier against the entry of heavy metal ions into cells. However, excessive accumulation of heavy metals within plants can lead to alterations in the spatial structure and physical properties of the cell wall, thereby affecting the capacity of plants to capture heavy metals. Proline (Pro) is involved in the synthesis of the cell wall, modulating the stability and integrity of its structure. Extensins, core proteins that maintain the cell wall structure, are proline/hydroxyproline-rich glycoproteins that contain the characteristic sequence Ser-[Pro]3–5. They act as intermediates in the regulation of biological processes such as cell wall synthesis, assembly, and signal transduction, typically forming a network structure of cell wall proteins through cross-linking with pectin. This network is essential for the self-assembly expansion of the plant cell wall and plays an indispensable role in cell wall stress signal transduction through its interaction with intracellular signalling molecules. However, the mechanisms by which Pro affects the synthesis of cell wall structural proteins, cell wall assembly, and the sensing of cell wall stress under heavy metal stress remain unclear. This review, from the perspectives of biochemistry and molecular biology, comprehensively elaborates on the impact of Pro and Pro-rich proteins on the structure and function of the cell wall. These findings emphasize the mechanism by which Pro enhances the ability of the cell wall to capture heavy metals, providing new research ideas for the use of genetic engineering to manipulate cell wall synthesis and repair, thereby reducing the phytotoxicity of heavy metals.

ABSTRACT: The S2 subunit of infectious bronchitis virus (IBV) is a heavily glycosylated protein that can impact various characteristics of the virus. It is currently known that N-glycosylation modifications are predominantly located on the S2 subunit. However, the exact role of their N-glycosylation modification remains undisclosed. To elucidate the function of these N-glycosylation sites, we identified 14 common sites distributed on the S2 subunit of the 5 genotypes of IBV in present study. Subsequently, we selected 7 sites to generate mutants and assessed their impact on viral virulence, replication ability, and antigenicity. Our finding revealed that only 2 substitutions, N545S and K717N, increased the viral replication titer and antigenicity, and ultimately the pathogenicity in chicks. To delve into the mechanisms underlying this increased pathogenicity, we discovered that K717N can change the structure of antigenic epitopes. The N545S substitution not only influenced antigenic epitope structure, but also enhanced the ability of the virus to enter CEKs during the early stages of viral replication. These results suggest that the enhanced viral pathogenicity associated with N545S and K717N substitutions is multifaceted, with acceleration of the viral membrane fusion process and alterations in epitope structure representing crucial factors in the capability of N-glycosylation modifications to boost viral virulence. These insights provide valuable guidance for the efficient development of live attenuated vaccines.

Abstract Background IL-15 plays a vital role in enhancing NK cell- and T-cell-mediated antitumor immune responses; however, the direct effect of IL-15 on tumor cells has not been fully elucidated. Herein, we investigated the effect of IL-15 on lung adenocarcinoma cells. Methods Silencing and overexpression techniques were used to modify endogenous IL-15 expression in tumor cells. Transwell assays were used to assess tumor cell migration and invasion; a live-cell analysis system was used to evaluate cell motility; cellular morphological changes were quantified by confocal fluorescence microscopy; the molecular mechanisms underlying the effect of IL-15 on tumor cells were analyzed by western blotting; and RhoA and Cdc42 activities were evaluated by a pulldown assay. NCG and C57BL/6 mouse models were used to evaluate the functions of IL-15 in vivo. Results Cancer cell-intrinsic IL-15 promoted cell motility and migration in vitro and metastasis in vivo via activation of the AKT-mTORC1 pathway; however, exogenous IL-15 inhibited cell motility and migration via suppression of the RhoA-MLC2 axis. Mechanistic analysis revealed that both the intracellular and extracellular IL-15-mediated effects required the expression of IL-15Rα by tumor cells. Detailed analyses revealed that the IL-2/IL-15Rβ and IL-2Rγ chains were undetected in the complex formed by intracellular IL-15 and IL-15Rα. However, when exogenous IL-15 engaged tumor cells, a complex containing the IL-15Rα, IL-2/IL-15Rβ, and IL-2Rγ chains was formed, indicating that the differential actions of intracellular and extracellular IL-15 on tumor cells might be caused by their distinctive modes of IL-15 receptor engagement. Using a Lewis lung carcinoma (LLC) metastasis model, we showed that although IL-15 overexpression facilitated the lung metastasis of LLC cells, IL-15-overexpressing LLC tumors were more sensitive to anti-PD-L1 therapy than were IL-15-wild-type LLC tumors via an enhanced antitumor immune response, as evidenced by their increased CD8+ T-cell infiltration compared to that of their counterparts. Conclusions Cancer cell-intrinsic IL-15 and exogenous IL-15 differentially regulate cell motility and migration. Thus, cancer cell-intrinsic IL-15 acts as a double-edged sword in tumor progression. Additionally, high levels of IL-15 expressed by tumor cells might improve the responsiveness of tumors to immunotherapies.

Objective Degenerative thoracolumbar hyperkyphosis (DTH) is a disease that negatively affects individual health and requires surgical intervention, yet the ideal surgical approach and complications, especially distal junctional failures (DJF), remain poorly understood. This study aims to investigate DJF in DTH and to identify the risk factors for DJF so that we can improve surgical decision‐making, and advance our knowledge in the field of spinal surgery to enhance patient outcomes. Methods This study retrospectively reviewed 78 cases (late osteoporotic vertebral compression fracture [OVCF], 51; Scheuermann's kyphosis [SK], 17; and degenerative disc diseases [DDD], 10) who underwent corrective surgery in our institute from 2008 to 2019. Clinical outcomes were assessed using health‐related quality of life (HRQOL) measures, including the visual analogue scale (VAS) scores for back and leg pain, the Oswestry disability index (ODI), and the Japanese Orthopaedic Association (JOA) scoring system. Multiple radiographic parameters, such as global kyphosis (GK) and thoracolumbar kyphosis (TLK), were assessed to determine radiographic outcomes. Multivariate logistic regression analysis was employed to identify the risk factors associated with DJF. Results HRQOL improved, and GK, TLK decreased at the final follow‐up, with a correction rate of 67.7% and 68.5%, respectively. DJF was found in 13 of 78 cases (16.7%), two cases had wedging in the disc (L3‐4) below the instrumentation, one case had a fracture of the lowest instrumented vertebrae (LIV), one case had osteoporotic fracture below the fixation, nine cases had pull‐out or loosening of the screws at the LIV and three cases (23.1%) required revision surgery. The DJF group had older age, lower computed tomography Hounsfield unit (CT HU), longer follow‐up, more blood loss, greater preoperative sagittal vertical axis (SVA), and poorer postoperative JOA and VAS scores (back). The change in TLK level was larger in the non‐DJF group. Post‐sagittal stable vertebrae (SSV) moved cranially compared with pre‐SSV. Conclusion Age, CT HU, length of follow‐up, estimated blood loss, and preoperative SVA were independent risk factors for DJF. We recommend fixation of the two vertebrae below the apex vertebrae for DTH to minimize surgical trauma.

The interactions between plants and herbivorous insects are complex and involve multiple factors, driving species formation and leading to the beginning of co-evolution and diversification of plant and insect molecules. Various molecular processes regulate the interactions between plants and herbivorous insects. Here, we discuss the molecular patterns of plant perception of herbivorous insect feeding through activation of early signaling components, crosstalk of plant defense network composed of multiple plant hormones, and various adaptive changes in insect responses to plant defenses. Both plant defenses and insect counter-defenses are molecular adaptation processes to each other. Molecular models of plant-herbivorous insect interactions can more intuitively help us to understand the co-evolutionary arms race between plants and herbivorous insects. These results will provide detailed evidence to elucidate and enrich the interaction network of plant-herbivorous insects.

Fusarium infection of wheat can lead to scab, mycotoxin contamination and yield reduction. Fusarium is a serious threat to food security. In this study, the Fusarium strains in wheat were isolated and identified. The three strains N1, N2 and N3 belonged to Fusarium graminearum, Fusarium asiaticum and Fusarium culmatum, respectively. The production of zearalenone, vomitoxin and fumonisin by the three strains was analyzed by toxin-producing gene detection and mycotoxin detection. The results showed that N1 and N3 could produce zearalenone and vomitoxin, but did not produce fumonisin, while N2 did not produce these three toxins. In this study, ozone and chlorine dioxide were further used for gas fumigation to explore the effect of gas fumigation on the three strains isolated. By observing the spore morphology, mycelium length and mycelium morphology, the results showed that chlorine dioxide fumigation could effectively inhibit the growth of mycelium and spore germination, while ozone could only inhibit spore germination and had no obvious inhibitory effect on the growth of mycelium.

Summary: Tracking the localization and proximal interaction partners of endogenous proteins provides valuable functional insight. Here, we present a protocol for CRISPR-based endogenous protein tagging in mammalian cells. We describe steps for endogenously tagging human TSC22D2 and MAP4, including designing Cas9 and Cas12a guides for knockin, modularized repair template design and cloning, and procedures for lipid transfection and electroporation. This protocol accommodates Cas nucleases in plasmid expression or ribonucleoprotein complex (RNP) formats. This “endo-tagging” approach offers flexibility and broad applicability.For complete details on the use and execution of this protocol, please refer to Xiao et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.