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With the increasing demand for high-performance passive nonlinear photonic devices, significant progress has been made in spatial self-phase modulation (SSPM) based on 2D nanomaterials in all-optical switches, logic gates, and information converters in recent years. However, there are still challenges in improving the responsiveness of photonic devices. In this work, we prepared a heterojunction of Ag nanoparticles deposited on the surface of violet phosphorus nanosheets (VP Ns), investigated their SSPM, and demonstrated their performance in all-optical switches. The SSPM experimental results show that compared with pure VP Ns at the same light intensity, both the maximum number and the formation time of self-diffraction rings in Ag/VP heterojunctions increase, and the nonlinear refractive index is approximately doubled. The main reason for optical nonlinearity enhancement is that the internal electric field in the heterojunction strengthens the mobility of the photogenerated carrier, thereby enhancing its optical nonlinearity. In particular, we demonstrate the performance of all-optical switches based on SSPM by utilizing the superior optical nonlinearity of Ag/VP heterojunctions. It is shown that with the increase of low-dose Ag content in heterojunctions, the switching time in the all-optical switch becomes shorter and the maximum number of self-diffraction rings of the signal light increases, although the quality of self-diffraction rings slightly decreases due to the scattering of Ag particles. The results contribute to the design and implementation of high-performance nonlinear photonic devices, based on the use of heterojunctions with low-cost preparation and a high nonlinear refractive index.

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STUDY QUESTION: Do biallelic deleterious variants of Calreticulin 3 (CALR3) cause fertilization failure (FF), resulting in male infertility in humans? SUMMARY ANSWER: Biallelic mutations in CALR3 were identified in two infertile men from unrelated families and were shown to cause FF associated with failed sperm-zona pellucida (ZP) binding. WHAT IS KNOWN ALREADY: In male mice, the Calr3-knockout has been reported to cause male infertility and FF. However, the mechanism behind this remains unclear in humans. STUDY DESIGN, SIZE, DURATION: Sequencing studies were conducted in a research hospital on samples from Han Chinese families with primary infertility and sperm head deformations to identify the underlying genetic causes. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data from two infertile probands characterized by sperm head deformation were collected through in silico analysis. Sperm cells from the probands were characterized using light and electron microscopy and used to verify the pathogenicity of genetic factors through functional assays. Subzonal insemination (SUZI) and IVF assays were performed to determine the exact pathogenesis of FF. ICSI were administered to overcome CALR3-affected male infertility. MAIN RESULTS AND THE ROLE OF CHANCE: Novel biallelic deleterious mutations in CALR3 were identified in two infertile men from unrelated families. We found one homozygous frameshift CALR3 mutation (M1: c.17_27del, p.V6Gfs*34) and one compound heterozygous CALR3 mutation (M2: c.943A>G, p.N315D; M3: c.544T>C, p.Y182H). These mutations are rare in the general population and cause acrosomal ultrastructural defects in affected sperm. Furthermore, spermatozoa from patients harbouring the CALR3 mutations were unable to bind to the sperm-ZP or they disrupted gamete fusion or prevented oocyte activation. Molecular assays have revealed that CALR3 is crucial for the maturation of the ZP binding protein in humans. Notably, the successful fertilization via SUZI and ICSI attempts for two patients, as well as the normal expression of PLCζ in the mutant sperm, suggests that ICSI is an optimal treatment for CALR3-deficient FF. LIMITATIONS, REASONS FOR CAUTION: The results are based on sperm-related findings from two patients. Further studies are required to gain insight into the developmental stage and function of CALR3 in human testis. WIDER IMPLICATIONS OF THE FINDINGS: Our findings highlight the underlying risk of FF associated with sperm defects and provide a valuable reference for personalized genetic counselling and clinical treatment of these patients. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the National Key R&D Program of China (2021YFC2700901), Hefei Comprehensive National Science Center Medical-Industrial Integration Medical Equipment Innovation Research Platform Project (4801001202), the National Natural Science Foundation of China (82201803, 82371621, 82271639), Foundation of the Education Department of Anhui Province (gxgwfx2022007), Key Project of Natural Science Research of Anhui Educational Committee (2023AH053287), and the Clinical Medical Research Transformation Project of Anhui Province (202204295107020037). The authors declare no competing interests. TRIAL REGISTRATION NUMBER: N/A.

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PURPOSE: Pituitary neuroendocrine tumors (PitNETs) with invasion of the cavernous sinus (CS) are particularly challenging to treat. Tumor associated fibroblasts (TAFs) are recognized for their pivotal role in reprogramming extracellular matrix (ECM). Herein, we aimed to explore the potential involvement of TAFs in ECM reprogramming and elucidate the underlying mechanism involved. METHODS: We applied dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to measure tumor vessel permeability and applied atomic force microscopy (AFM) to measure the matrix stiffness of PitNETs located in both CS and sella turcica (ST). Western blotting, immunofluorescence, immunohistochemistry, and quantitative RT-PCR were utilized to analyze the ECM components. Proteomic biochemical analysis was utilized to uncover potential mechanisms governing ECM dynamics. RESULTS: We found that PitNETs in the CS were stiffer than those in the ST. Increased ECM stiffness within the CS facilitated the acquisition of stem-like properties, enhanced proliferation, and induced epithelial-to-mesenchymal transition (EMT) of GH3 cells. Furthermore, the expression levels of lysyl oxidase (LOX), matrix metallopeptidase 2 (MMP2) and MMP9 in pituitary adenoma cells increased in the stiffer matrix. Proteomic analysis suggested TAFs were activated in the CS area and contributed enhanced matrix stiffness by secreting Col-1 and Col-3. Furthermore, mTOR pathway was activated under higher matrix stiffness and the migration and invasion of GH3 cells be repressed by mTOR inhibitor. CONCLUSION: These findings demonstrated that activated TAFs contributed to stiffer matrix and increased ECM stiffness stimulating mTOR pathway in pituitary tumor cells. Our study indicated that mTOR inhibitor was a promising treatment strategy from the standpoint of PitNET biomechanical properties.

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The rapid growth of offshore wind farms (OWFs) is driven by concerns for energy security and climate change mitigation. However, their impact on marine environments remains poorly understood due to limited research. This study analyzes the effects of an OWF along China's Jiangsu Coast on seawater quality using data from different development phases. Results show the major pollutants were different across phases. Heavy metal pollution reached alert levels during construction compared to the safe levels observed in the pre-construction and operational phases, mainly due to increases in Pb, Cd, and Hg concentrations. Eutrophication was mild throughout all periods but exhibited a continuous decrease, primarily attributed to reductions in PH and COD concentrations. As a result, the comprehensive pollution level during construction was increased, but it was improved to a clean level during the operational phase. Besides, significant variations were observed in the spatial distribution patterns of major pollutant indices across different scenarios. These changes may stem from a combination effect of land-based pollution, aquaculture, OWF-induced disturbances to atmosphere and hydrodynamics, OWF-related drain and leakage contamination, and marine management policies. Understanding these effects informs OWF optimization, rational wind resource utilization, and marine ecology protection.

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OBJECTIVES: This study aimed to compare plasma concentrations of anesthetic drugs administered during Cesarean section with low Apgar score in neonates deliveried under general anesthesia and analyze associated risk factors. METHODS: Data from 76 neonates undergoing Cesarean section under general anesthesia with blood concentrations of anesthetic drugs were analyzed. A low Apgar score was defined as ≤ 7. Perioperative maternal and neonatal data were collected and analyzed. Neonates were divided into a control group (Group CON, n = 65) and a low Apgar score group (Group LAS, n = 11) based on Apgar score. RESULTS: There were no significant differences in the plasma concentrations of anesthetic drugs in maternal artery, umbilical vein or umbilical artery blood between the two groups. Risk factors for neonatal low Apgar scores during Cesarean section under general anesthesia were premature delivery (aOR 10.2, 95% CI = 1.8-56.9) and preoperative fetal distress (aOR 9.6, 95% CI = 1.3-69.0). The prediction model was: probability = 1/(e­Y), Y= -4.607 + 2.318× (premature delivery) + 2.261× (fetal distress) (yes = 1, no = 0). The Hosmer-Lemeshow test showed χ²= 9.587, P = 0.213, and the area under the curve (AUC) was 0.850 (0.670 ~ 1.000). With a cutoff value of 0.695, sensitivity and specificity were 81.8% and 87.7%, respectively. CONCLUSIONS: There was no correlation between blood concentration of general anesthetic drugs and Apgar score or occurrence of neonatal low Apgar scores. Premature delivery and preoperative fetal distress were identified as independent risk factors for neonatal low Apgar scores after Cesarean section under general anesthesia.

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OBJECTIVE: To establish a nomogram model for predicting the risk of sepsis in diabetic foot patients, and to provide reference for clinical prevention and treatment. METHODS: The clinical data of 430 patients with diabetic foot who were hospitalized in Chu Hsien-I Memorial Hospital of Tianjin Medical University from January 2022 to March 2023 were reviewed and collected, including age, gender, past medical history, smoking and drinking history, family history, diabetes course, Texas grade of diabetic foot and laboratory indicators within 24 hours after admission. Patients were divided into sepsis group and non-sepsis group according to the presence or absence of sepsis during hospitalization. The differences in clinical data between the two groups were compared. Multivariate Logistic regression analysis was used to screen the influencing factors of sepsis in patients with diabetic foot during hospitalization, and a nomogram predictive model was established. The performance of the prediction model was evaluated by receiver operator characteristic curve (ROC curve), calibration curve and decision curve analysis (DCA). Internal validation was performed by using Bootstrap method. RESULTS: A total of 430 patients were enrolled, among which 90 patients developed sepsis during hospitalization and 340 patients did not. There were statistically significant differences in diabetes course, Texas grade of diabetic foot, white blood cell count (WBC), neutrophil count (NEU), lymphocyte count (LYM), neutrophil to lymphocyte ratio (NLR), hemoglobin (Hb), albumin (Alb), glycosylated hemoglobin (HbA1c), C-reactive protein (CRP), and blood urea nitrogen (BUN) between the two groups. Multivariate Logistic regression analysis showed that diabetes course [odds ratio (OR) = 2.774, 95% confidence interval (95%CI) was 1.053-7.308, P = 0.039], Texas grade of diabetic foot (OR = 2.312, 95%CI was 1.014-5.273, P = 0.046), WBC (OR = 1.160, 95%CI was 1.042-1.291, P = 0.007), HbA1c (OR = 1.510, 95%CI was 1.278-1.784, P < 0.001), CRP (OR = 1.007, 95%CI was 1.000-1.014, P = 0.036) were independent risk factors for sepsis in patients with diabetic foot during hospitalization, while Alb was a protective factor (OR = 0.885, 95%CI was 0.805-0.972, P = 0.011). A nomogram predictive model was constructed based on the above 6 indicators. The ROC curve showed that the area under ROC curve (AUC) of the nomogram predictive model for identifying the sepsis patients was 0.919 (95%CI was 0.889-0.948). The AUC of the nomogram predictive model after internal verification was 0.918 (95%CI was 0.887-0.946). Hosmer-Lemeshow test showed χ 2 = 2.978, P = 0.936, indicating that the calibration degree of the predictive model was good. Calibration curve showed that the predicted probability of sepsis was in good agreement with the actual probability. DCA curve showed that the nomogram predictive model had good clinical usefulness. CONCLUSIONS: The nomogram predictive model based on the risk factors of diabetes course, Texas grade of diabetic foot, WBC, HbA1c, CRP and Alb has good predictive value for the occurrence of sepsis in patients with diabetic foot during hospitalization, which is helpful for clinical screening of the possibility of diabetic foot patients progressing to sepsis, and timely personalized intervention for different patients.

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As one of the common malignancies that threaten human life, bladder cancer occurs frequently with a high mortality rate in the world, due to its invasion, recurrence and drug resistance. Natural products from marine microorganisms are becoming the hotspots in discovery of new candidate drug entities, especially in the area of cancer. Brefeldin A (BFA) is a natural Arf-GEFs inhibitor, but due to the low aqueous solubility, strong toxicity, and poor bioavailability, it is urgent to conduct structural optimization research. Herein, a new BFA pyridine acrylate derivative CHNQD-01281 with improved solubility was prepared and found to exert moderate to strong antiproliferative activity on a variety of human cancer cell lines. It was noteworthy that CHNQD-01281 was most sensitive to two bladder cancer cell lines T24 and J82 (IC50 = 0.079 and 0.081 µmol/L) with high selectivity index (SI = 14.68 and 14.32), suggesting a superior safety to BFA. In vivo studies revealed that CHNQD-01281 remarkably suppressed tumor growth in a T24 nude mice xenograft model (TGI = 52.63%) and prolonged the survival time (ILS = 68.16%) in an MB49 allogeneic mouse model via inducing infiltration of cytotoxic T cells. Further mechanism exploration indicated that CHNQD-01281 regulated both EGFR/PI3K/AKT and EGFR/ERK pathways and mediated the chemotactic effect of chemokines on immune effector cells. Overall, CHNQD-01281 may serve as a potential therapeutic agent for bladder cancer through multiple mechanisms. Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-024-00246-w.

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BACKGROUND: This study aims to compare the differences between unattended and conventional blood pressure measurements in hospitalized hypertensive patients. METHODS: In fall of 2019, hypertensive patients at Ruijin Hospital underwent two rounds of unattended and conventional (nurse-monitored) blood pressure measurement. Both rounds used the same electronic blood pressure monitor with measurements taken three times, 30 s apart. Comparison was made using intra-class correlation coefficients, Bland-Altman plots, paired t-tests, etc. RESULTS: Among the 92 subjects in the study, the median age was 50 years old, with women accounting for 33.7%. Among the subjects, the median duration of hypertension was 8.0 years. The prevalence of diabetes, coronary heart disease, and stroke were 26.1%, 5.4%, and 6.5%, respectively. Whether unattended or conventional measurements were taken first, the average blood pressure measured first was slightly higher than the one measured later, but the difference was within 1-2 mmHg. Except that the average DBP during the round of conventional blood pressure measurements was significantly reduced by 1.6 mmHg compared to the conventional DBP, there were no other significant differences. Subgroup analysis by age, gender, BMI, and diabetes showed no significant difference in blood pressure measurement results between unattended and conventional methods. CONCLUSION: No significant difference was observed between unattended and conventional methods of blood pressure measurement in hospitalized hypertensive patients. Unattended blood pressure measurement can be adopted as the current standard for blood pressure management in hospitalized patients.

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This study aims to elucidate the pivotal role of aldolase A (ALDOA) in retinoblastoma (RB) and evaluate the potential of the ALDOA inhibitor itaconate in impeding RB progression. Utilizing single-cell RNA sequencing, ALDOA consistently exhibits overexpression across diverse cell types, particularly in cone precursor cells, retinoma-like cells, and retinoblastoma-like cells. This heightened expression is validated in RB tissues and cell lines. ALDOA knockdown significantly diminishes RB cell viability, impedes colony formation, and induces notable metabolic alterations. RNA-seq analysis identifies SUSD2, ARHGAP27, and CLK2 as downstream genes associated with ALDOA. The application of itaconate demonstrates efficacy in inhibiting RB cell proliferation, validated through in vitro and in vivo models. This study emphasizes ALDOA as a promising target for innovative RB therapies, with potential implications for altering tumor energy metabolism.

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Background: Kawasaki disease (KD) is a systemic vasculitis primarily affecting the coronary arteries in children. Despite growing attention to its symptoms and pathogenesis, the exact mechanisms of KD remain unclear. Mitophagy plays a critical role in inflammation regulation, however, its significance in KD has only been minimally explored. This study sought to identify crucial mitophagy-related biomarkers and their mechanisms in KD, focusing on their association with immune cells in peripheral blood. Methods: This research used four datasets from the Gene Expression Omnibus (GEO) database that were categorized as the merged and validation datasets. Screening for differentially expressed mitophagy-related genes (DE-MRGs) was conducted, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. A weighted gene co-expression network analysis (WGCNA) identified the hub module, while machine-learning algorithms [random forest-recursive feature elimination (RF-RFE) and support vector machine-recursive feature elimination (SVM-RFE)] pinpointed the hub genes. Receiver operating characteristic (ROC) curves were generated for these genes. Additionally, the CIBERSORT algorithm was used to assess the infiltration of 22 immune cell types to explore their correlations with hub genes. Interactions between transcription factors (TFs), genes, and Gene-microRNAs (miRNAs) of hub genes were mapped using the NetworkAnalyst platform. The expression difference of the hub genes was validated using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Results: Initially, 306 DE-MRGs were identified between the KD patients and healthy controls. The enrichment analysis linked these MRGs to autophagy, mitochondrial function, and inflammation. The WGCNA revealed a hub module of 47 KD-associated DE-MRGs. The machine-learning algorithms identified cytoskeleton-associated protein 4 (CKAP4) and serine-arginine protein kinase 1 (SRPK1) as critical hub genes. In the merged dataset, the area under the curve (AUC) values for CKAP4 and SRPK1 were 0.933 [95% confidence interval (CI): 0.901 to 0.964] and 0.936 (95% CI: 0.906 to 0.966), respectively, indicating high diagnostic potential. The validation dataset results corroborated these findings with AUC values of 0.872 (95% CI: 0.741 to 1.000) for CKAP4 and 0.878 (95% CI: 0.750 to 1.000) for SRPK1. The CIBERSORT analysis connected CKAP4 and SRPK1 with specific immune cells, including activated cluster of differentiation 4 (CD4) memory T cells. TFs such as MAZ, SAP30, PHF8, KDM5B, miRNAs like hsa-mir-7-5p play essential roles in regulating these hub genes. The qRT-PCR results confirmed the differential expression of these genes between the KD patients and healthy controls. Conclusions: CKAP4 and SRPK1 emerged as promising diagnostic biomarkers for KD. These genes potentially influence the progression of KD through mitophagy regulation.

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Background: Limited evidence exists regarding the effects of non-invasive ventilation (NIV) on the prognosis of patients with concomitant chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA), also known as overlap syndrome (OS). This study aimed to assess whether NIV alongside standard care could improve the prognosis of this cohort. Methods: We retrospectively collected data from 229 patients with severe OS treated in Beijing Anzhen Hospital between January 1, 2016 and January 1, 2020, with follow-up until December 1, 2023. All patients were recommended usual care and NIV and were subsequently divided into non-NIV (usual care only) and NIV groups (usual care plus NIV) per their willingness and adherence to NIV. Endpoints included all-cause and acute exacerbation of COPD (AECOPD)-associated death and re-hospitalization. Multivariate analyses were used to determine the relationship of NIV with prognosis. Results: The follow-up lasted for a median of 760 days (interquartile range, 245-1,374 days). Patients in the NIV group showed lower rates of all-cause (37.5% vs. 65.1%, P<0.001) and AECOPD-associated (31.7% vs. 58.7%, P<0.001) death compared with patients in the non-NIV group. Compared with usual care only, NIV treatment was associated with significant reduction in all-cause death [relative risks (RR) =0.459, 95% confidence interval (CI): 0.315-0.668, P<0.001], AECOPD-associated mortality (RR =0.424, 95% CI: 0.283-0.635, P<0.001), and re-hospitalization for all causes (RR =0.455, 95% CI: 0.342-0.605, P<0.001) and for AECOPD (RR =0.421, 95% CI: 0.308-0.575, P<0.001) in Cox hazards models, with significance persisting after multivariable adjustment. Conclusions: NIV may improve outcomes and survival in patients with severe OS of comorbid COPD and OSA. Confirmatory studies are needed to prove benefits.

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Abscisic acid (ABA) is the primary preventing factor of seed germination, which is crucial to plant survival and propagation. ABA-induced seed germination inhibition is mainly mediated by the dimeric PYR/PYL/RCAR (PYLs) family members. However, little is known about the relevance between dimeric stability of PYLs and seed germination. Here, we reveal that stabilization of PYL dimer can relieve ABA-induced inhibition of seed germination using chemical genetic approaches. Di-nitrobensulfamide (DBSA), a computationally designed chemical probe, yields around ten-fold improvement in receptor affinity relative to ABA. DBSA reverses ABA-induced inhibition of seed germination mainly through dimeric receptors and recovers the expression of ABA-responsive genes. DBSA maintains PYR1 in dimeric state during protein oligomeric state experiment. X-ray crystallography shows that DBSA targets a pocket in PYL dimer interface and may stabilize PYL dimer by forming hydrogen networks. Our results illustrate the potential of PYL dimer stabilization in preventing ABA-induced seed germination inhibition.

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BACKGROUND: Ribosome profiling (or Ribo-seq) is a technique that provides genome-wide information on the translational landscape (translatome). Across different plant studies, variable methodological setups have been described which raises questions about the general comparability of data that were generated from diverging methodologies. Furthermore, a common problem when performing Ribo-seq are abundant rRNA fragments that are wastefully incorporated into the libraries and dramatically reduce sequencing depth. To remove these rRNA contaminants, it is common to perform preliminary trials to identify these fragments because they are thought to vary depending on nuclease treatment, tissue source, and plant species. RESULTS: Here, we compile valuable insights gathered over years of generating Ribo-seq datasets from different species and experimental setups. We highlight which technical steps are important for maintaining cross experiment comparability and describe a highly efficient approach for rRNA removal. Furthermore, we provide evidence that many rRNA fragments are structurally preserved over diverse nuclease regimes, as well as across plant species. Using a recently published cryo-electron microscopy (cryo-EM) structure of the tobacco 80S ribosome, we show that the most abundant rRNA fragments are spatially derived from the solvent-exposed surface of the ribosome. CONCLUSION: The guidelines presented here shall aid newcomers in establishing ribosome profiling in new plant species and provide insights that will help in customizing the methodology for individual research goals.

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Systemic infection with Candida albicans poses a significant risk for people with weakened immune systems and carries a mortality rate of up to 60%. However, current therapeutic options have several limitations, including increasing drug tolerance, notable off-target effects, and severe adverse reactions. Over the past four decades, the progress in developing drugs to treat Candida albicans infections has been sluggish. This comprehensive review addresses the limitations of existing drugs and summarizes the efforts made toward redesigning and innovating existing or novel drugs through nanotechnology. The discussion explores the potential applications of nanomedicine in Candida albicans infections from four perspectives: nano-preparations for anti-biofilm therapy, innovative formulations of "old drugs" targeting the cell membrane and cell wall, reverse drug resistance therapy targeting subcellular organelles, and virulence deprivation therapy leveraging the unique polymorphism of Candida albicans. These therapeutic approaches are promising to address the above challenges and enhance the efficiency of drug development for Candida albicans infections. By harnessing nano-preparation technology to transform existing and preclinical drugs, novel therapeutic targets will be uncovered, providing effective solutions and broader horizons to improve patient survival rates.

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Background: Nitroglycerin administration prior to examination improves stenosis assessment of coronary computed tomography (CT) angiography (CCTA). However, whether nitroglycerin influences CT-derived fractional flow reserve (FFR, CT-FFR) evaluation remains unclear. This study aimed to investigate the effect of nitroglycerin on diagnostic performance of CT-FFR. Methods: In this single-center retrospective study, 107 consecutive patients suspected of coronary artery disease (CAD) with nitroglycerin administration prior to CCTA in 2019 were matched to 107 patients without nitroglycerin in 2016 from Fuwai Hospital. All patients underwent CCTA and invasive FFR in a month. Vessel-based and patient-based accuracy and diagnostic performance of CT-FFR were compared between the two groups, as well as image quality, coronary artery diameter and evaluability. Quantitative variables were compared by Kruskal-Wallis H test. Categorical variables and rates were compared by χ2 test or Fisher exact test. Results: A total of 214 patients (56.1±8.9 years, 155 male) with 237 target lesion vessels were analyzed, including 120 vessels in nitroglycerin and 117 vessels in non-nitroglycerin group. Per-vessel based accuracy of CT-FFR was higher in nitroglycerin group {80.0% [95% confidence interval (CI): 71.7-86.7%] vs. 68.4% (59.1-76.7%), P=0.041}. On a per-patient basis, nitroglycerin administration improved the accuracy [83.2% (74.7-89.7%) vs. 68.2% (58.5-76.9%), P=0.01], specificity [82.7% (69.7-91.8%) vs. 61.9% (48.8-73.9%), P=0.01], positive predictive value (PPV) [83.6% (73.6-90.4%) vs. 58.6% (50.0-66.9%), P=0.004], and area under the curve (AUC) [0.83 (0.75-0.89) vs. 0.71 (0.61-0.79), P=0.03] of CT-FFR. Vessel diameters (left main arteries: 4.3 vs. 3.8 mm, P<0.001; left anterior descending arteries: 3.1 vs. 2.9 mm, P=0.001; left circumflex arteries: 2.9 vs. 2.7 mm, P=0.01; right coronary arteries: 3.7 vs. 3.4 mm, P=0.001) and number of evaluable coronary arteries (11.0 vs. 8.0, P<0.001) were larger in nitroglycerin group. Conclusions: Nitroglycerin administration prior to CCTA has positive effects on diagnostic performance of CT-FFR.

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BACKGROUND: Lipid droplet (LD) is a metabolically active organelle, which changes dynamically with the metabolic state and energy requirements of cells. Proteins that either insert into the LD phospholipid monolayer or are present in the cytoplasm, playing a crucial role in lipid homeostasis and signaling regulation, are known as LD-associated proteins. METHODS: The keywords "lipid droplets" and "metabolic diseases" were used to obtain literature on LD metabolism and pathological mechanism. After searching databases including Scopus, OVID, Web of Science, and PubMed from 2013 to 2024 using terms like "lipid droplets", "lipid droplet-associated proteins", "fatty liver disease", "diabetes", "diabetic kidney disease", "obesity", "atherosclerosis", "hyperlipidemia", "natural drug monomers" and "natural compounds", the most common natural compounds were identified in about 954 articles. Eventually, a total of 91 studies of 10 natural compounds reporting in vitro or in vivo studies were refined and summarized. RESULTS: The most frequently used natural compounds include Berberine, Mangostin, Capsaicin, Caffeine, Genistein, Epigallocatechin-3-gallate, Chlorogenic acid, Betaine, Ginsenoside, Resveratrol. These natural compounds interact with LD-associated proteins and help ameliorate abnormal LDs in various metabolic diseases. CONCLUSION: Natural compounds involved in the regulation of LDs and LD-associated proteins hold promise for treating metabolic diseases. Further research into these interactions may lead to new therapeutic applications.

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Premature ovarian insufficiency (POI) is the main cause of infertility in women. Some cases of POI are thought to be caused by genetic defects and the clinical outcomes of these patients are unknown. Here, we performed whole-exome sequencing of the peripheral blood of a cohort of 55 subjects with POI and identified one heterozygous missense variant in FOXL2 (c.1045G>C; p.Arg349Gly) and two heterozygous missense variants in ERCC6 (c.379G>A; p.Val127Ile and c.4223A>C; p.Glu1408 Ala) in four POI patients. All of these heterozygous mutations were predicted to be deleterious and were parentally inherited from their heterozygous fathers. The mRNA and protein expression of FOXL2 and ERCC6 were absent or decreased in the patients. The patients carrying the variants of FOXL2 (c.1045G>C; p.Arg349Gly) and ERCC6 (c.379G>A; p.Val127Ile) failed to conceive in two and four assisted reproductive cycles, respectively. Another patient and her sister carrying the ERCC6 (c.4223A>C; p.Glu1408 Ala) variant achieved good clinical outcomes after assisted reproductive therapy. Our findings support the possible roles of FOXL2 and ERCC6 in POI and might contribute to the genetic counseling of POI patients.

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Long-term excessive use of fertilizers and intensive cultivation not only decreases soil organic carbon (SOC) and productivity, but also increases greenhouse gas emissions, which is detrimental to sustainable agricultural development. The purpose of this paper is to identify organic amendments suitable for winter wheat growth in the North China Plain by studying the effects of organic amendments on the economic benefits, carbon emissions, and carbon sequestration for winter wheat fields and to provide a theoretical basis for the wide application of organic amendments in agricultural fields. The two nitrogen rates were N0 (0 kg ha-1) and N240 (240 kg ha-1), and the four organic amendments were straw, manure, mushroom residue (M R), and biochar. The results showed that, compared to N0, N240 significantly increased the yield by 244.1-318.4% and the organic carbon storage by 16.7-30.5%, respectively, but increased the carbon emissions by 29.3-45.5%. In addition, soil carbon stocks increased with all three types of organic amendments compared to the straw amendment, with the biochar treatment being the largest, increasing carbon storage by 13.3-33.6%. In terms of yield and economic benefits, compared to the straw amendment, the manure and biochar amendments increased winter wheat yields by 0.0-1.5% and 4.0-13.3%, respectively, and M R slightly decreased wheat yield; only the economic benefit of the M R amendment was greater than that of the straw amendment, with an increase in economic benefit of 1.3% and 8.2% in the 2021-2022 and 2022-2023 seasons, respectively. Furthermore, according to the net ecosystem productivity (NEP), N0 was the source of CO2, while N240 was a sink of CO2. The TOPSIS results showed that N240 with a mushroom residue amendment could be recommended for increasing soil carbon stocks and economic benefits for winter wheat in the NCP and similar regions. Low-cost M R can increase farmer motivation and improve soil organic carbon, making a big step forward in the spread of organic materials on farmland.

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In order to ensure national grain and oil security, it is imperative to expand the soybean planting area in the Xinjiang region. However, the scarcity of water resources in southern Xinjiang, the relatively backward soybean planting technology, and the lack of a supporting irrigation system have negatively impacted soybean planting and yield. In 2022 and 2023, we conducted an experiment which included three irrigation amounts of 27 mm, 36 mm, and 45 mm and analyzed the changes in dry mass and yield. Additionally, we simulated the potential yield using the corrected DSSAT-CROPGRO-Soybean model and biomass based on the meteorological data from 1994 to 2023. The results demonstrated that the model was capable of accurately predicting soybean emergence (the relative root mean square error (nRMSE) = 0, the absolute relative error (ARE) = 0), flowering (nRMSE = 0, ARE = 2.78%), maturity (nRMSE = 0, ARE = 3.21%). The model demonstrated high levels of accuracy in predicting soybean biomass (R2 = 0.98, nRMSE = 20.50%, ARE = 20.63%), 0-80 cm soil water storage (R2 = 0.64, nRMSE = 7.78%, ARE = 3.24%), and yield (R2 = 0.81, nRMSE = 10.83%, ARE = 8.79%). The biomass of soybean plants increases with the increase in irrigation amount. The highest biomass of 63 mm is 9379.19 kg·hm-2. When the irrigation yield is 36-45 mm (p < 0.05), the maximum yield can reach 4984.73 kg·hm-2; the maximum efficiency of soybean irrigation water was 33-36 mm. In light of the impact of soybean yield and irrigation water use efficiency, the optimal irrigation amount for soybean cultivation in southern Xinjiang is estimated to be between 36 and 42 mm. The simulation results provide a theoretical foundation for soybean cultivation in southern Xinjiang.

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Solid tumours induce systemic immunosuppression that involves myeloid and T cells. B cell-related mechanisms remain relatively understudied. Here we discover two distinct patterns of tumour-induced B cell abnormality (TiBA; TiBA-1 and TiBA-2), both associated with abnormal myelopoiesis in the bone marrow. TiBA-1 probably results from the niche competition between pre-progenitor-B cells and myeloid progenitors, leading to a global reduction in downstream B cells. TiBA-2 is characterized by systemic accumulation of a unique early B cell population, driven by interaction with excessive neutrophils. Importantly, TiBA-2-associated early B cells foster the systemic accumulation of exhaustion-like T cells. Myeloid and B cells from the peripheral blood of patients with triple-negative breast cancer recapitulate the TiBA subtypes, and the distinct TiBA profile correlates with pathologic complete responses to standard-of-care immunotherapy. This study underscores the inter-patient diversity of tumour-induced systemic changes and emphasizes the need for treatments tailored to different B and myeloid cell abnormalities.