NT-pro-BNP Level is Related to Left Ventricular Remodeling in Patients With Primary Aldosteronism.

AIMS: To assess the relationship between the left ventricular remodeling parameters of cardiac magnetic resonance and NT-pro-BNP in patients with primary aldosteronism (PA). METHODS: Seventy-four PA and 39 essential hypertension patients were prospectively recruited and underwent cardiac magnetic resonance. Plasma NT-pro-BNP was measured before patients underwent cardiac magnetic resonance. Left ventricular remodeling parameters were defined as left ventricular function parameters, T1 mapping parameters, and strain parameters. Differences in continuous variables between two groups were analyzed using Student's t-test or Mann-Whitney U test. Differences in categorical variables between two groups were analyzed by chi-squared test. Spearman's correlation and linear regression were used to analyze the relationships between left ventricular remodeling parameters and plasma NT-Pro-BNP level. P<0.05 was considered as statistically significant. RESULTS: Patients with PA demonstrated higher NT-pro-BNP [86.0 (49.5, 145.5) vs. 45.0 (28.5, 73.5) pg/mL, P=0.001] and Native T1 (1227±41 vs. 1206±43 ms, P=0.015) level than essential hypertension patients. Compared to patients with normal NT-pro-BNP levels, those with abnormal levels demonstrated different left ventricular remodeling parameters. NT-pro-BNP level was independently related to native T1 (ß=0.316, P=0.006), extracellular volume (ß=0.419, P<0.001), short-axis global circumferential strain (ß=0.429, P<0.001), four-chamber global longitudinal strain (ß=0.332, P=0.002), and four-chamber global radial strain (ß=-0.334, P=0.004) in patients after adjusting for baseline characteristics. CONCLUSIONS: NT-pro-BNP level was related to left ventricular remodeling parameters derived from cardiac magnetic resonance in patients with PA. This result implies that clinicians should pay attention to NT-pro-BNP assessment in patients with PA in routine clinical assessment.

Limb circumference measurements contributing to the diagnosis of snake venom-induced compartment syndrome.

Background: The present study aimed to investigate the relationship between swollen limb circumference and compartment pressure after a snakebite and to evaluate the diagnostic value of the circumference difference between the healthy and affected sides and the circumference growth rate for snake venom-induced compartment syndrome (CS). Method: The study was based on a prospective cohort study of snakebite patients at the emergency department of West China Hospital from May 2021 to October 2022. The snakebite patients were divided into the CS and non-compartment syndrome (NCS) groups. The diagnostic value of the circumference of the swollen limb for the CS after snakebite was evaluated using a receiver-operating characteristic curve analysis, and the cut-off value of the circumference of the swollen limb for CS after snakebite was calculated with sensitivity and specificity. Result: The present study enrolled 115 patients with severely swollen limbs after snakebite. The mean age was 59.1 ± 13.6 years, with 58 (50.4 %) female cases and 57 (49.6 %) male cases. There were 33 (28.7 %) cases where the upper limbs were injured and 82 (71.3 %) cases where the lower limbs were injured. These patients were divided into CS (n = 19) and NCS (n = 96) groups. The area under the curve (AUC) for the 15 cm circumference difference and circumferential growth rate of the upper edge of the patella was 0.683 (95 % CI 0.508 to 0.858, P = 0.037), and 0.685 (95 % CI 0.512 to 0.858, P = 0.035). The optimal cut-off values for the 15 cm circumference difference and circumferential growth rate of the upper edge of the patella to distinguish CS and NCS were 2.8 cm (sensitivity = 76.9 %, specificity = 66.7 %) and 7 % (sensitivity = 76.9 %, specificity = 66.7 %), respectively. Conclusion: Limb circumference measurement is a non-invasive, convenient, effective, and repeatable bedside test that can assist clinicians in the early detection of suspected snake venom-induced CS in patients exhibiting limb swelling after snake bites.

Biochemical analyses reveal new insights into RCAN1/Rcn1 inhibition of calcineurin.

Calcineurin is a serine/threonine protein phosphatase that is highly conserved from yeast to human and plays a critical role in many physiological processes. Regulators of calcineurin (RCANs) are a family of endogenous calcineurin regulators, which are capable of inhibiting the catalytic activity of calcineurin in vivo and in vitro. In this study, we first characterized the biochemical properties of yeast calcineurin and its endogenous regulator Rcn1, a yeast homolog of RCAN1. Our data show that Rcn1 inhibits yeast calcineurin toward pNPP substrate with a noncompetitive mode; and Rcn1 binds cooperatively to yeast calcineurin through multiple low-affinity interactions at several docking regions. Next, we reinvestigated the mechanism underlying the inhibition of mammalian calcineurin by RCAN1 using a combination of biochemical, biophysical, and computational methods. In contrast to previous observations, RCAN1 noncompetitively inhibits calcineurin phosphatase activity toward both pNPP and phospho-RII peptide substrates by targeting the enzyme active site in part. Re-analysis of previously reported kinetic data reveals that the RCAN1 concentrations used were too low to distinguish between the inhibition mechanisms [Chan B et al. (2005) Proc Natl Acad Sci USA 102, 13075]. The results presented in this study provide new insights into the interaction between calcineurin and RCAN1/Rcn1.

The Methodological Quality of Observational Studies Examining the Risk of Pregnancy Drug Use on Congenital Malformations Needs Substantial Improvement: A Cross-Sectional Survey.

BACKGROUND AND OBJECTIVE: An increasing number of observational studies have investigated the risk of using drugs during pregnancy on congenital malformations. However, the credibility of the causal relationships drawn from these studies remains uncertain. This study aims to evaluate the potential methodological issues in existing observational studies. METHODS: We used a stepwise approach to investigate this issue. First, we identified observational studies published in 2020 that examined the risk of congenital malformations associated with medication use during pregnancy. We assessed the methodological characteristics for establishing causality, including study design, confounding control, and sensitivity analysis, and compared them between "core clinical journals" and "general journals." For studies reporting an increased risk of congenital malformations in core clinical journals, we searched for subsequent studies addressing the same research question published between January 2021 and May 2023 to assess the consistency of the literature. RESULTS: A total of 40 eligible studies were published in 2020, primarily focused on the safety of vitamin B12 and folic acid (n = 4), antidepressants (n = 4), and others (n = 32). Our findings suggest that only two (5.00%) studies used causal models to guide the identification of confounding, and only eight (20.00%) studies assessed the potential dose-response relationship. In all, 15 (37.50%) studies used propensity score analysis strategy to achieve "mimic-randomization." In addition, 22 studies (55.00%) performed sensitivity analyses, while 10 (45.45%) showed inconsistency with the primary outcome. Furthermore, 5 studies reported positive outcomes, whereas only 1 out of 11 studies demonstrated a positive correlation between drug usage during pregnancy and major malformations in subsequent studies. CONCLUSION: A significant portion of the studies has failed to sufficiently consider the essential methodological characteristics required to improve the credibility of causal inferences. The increased risk of congenital malformations documented in core clinical journal was not adequately replicated in subsequent studies.

[Mechanism of Liangfang Wenjing Decoction in treatment of hypoxia on endometriosis with cold coagulation and blood stasis by regulating CHCHD4 expression].

To explore the mechanism of Liangfang Wenjing Decoction regulating coiled-coil-helix coiled-coil-helix domain containing 4(CHCHD4) in the treatment of hypoxia on endometriosis(EMs) with cold coagulation and blood stasis. The rat model of cold coagulation and blood stasis syndrome was prepared by the ice-water bath method, and then the EMs model was established by autologous intimal transplantation. The rats were randomly divided into model group, low, medium, and high(4.7, 9.4, and 18.8 g·kg~(-1)) dose groups of Liangfang Wenjing Decoction, Shaofu Zhuyu Decoction group, and sham group, with 10 rats in each group. The rats were given intragastric administration for four weeks. During the modeling, the general condition and vaginal smear of rats were observed, and the blood flow of ears and uterus were detected by laser speckle contrast imaging(LSCI) to judge the syndrome of cold coagulation and blood stasis. After the administration, the general condition of the rats was observed, and the area of ectopic lesions was measured by caliper. The localization and expression of CHCHD4 and hypoxia inducible factors-1α(HIF-1α) were detected by immunohistochemistry, and the mRNA and protein expressions of CHCHD4 and HIF-1α were detected by real-time quantitative polymerase chain reaction(RT-qPCR) and Western blot. The primary culture of ectopic endometrial stromal cells(ESCs) from EMs patients was performed, and the CHCHD4 overexpression plasmid was constructed and transfected to establish the ESCs model of CHCHD4 overexpression. The cells were divided into the control group, CHCHD4 overexpression group, CHCHD4 overexpression+control serum group, and CHCHD4 overexpression+Liangfang Wenjing Decoction serum group. The protein expression of CHCHD4 and HIF-1α was detected by Western blot, and the glucose consumption and lactic acid level were detected. The cell proliferation was detected by MTT assay. The experiment found that compared with normal rats, the modeling rats showed symptoms of cold coagulation and blood stasis, such as mental malaise, reduced diet and drinking water, disordered estrous cycle, and blocked blood circulation in ears and uterine microvessels. Compared with the sham group, the ectopic lesions in the model group were uplifted, and the mRNA and protein expressions of CHCHD4 and HIF-1α were significantly increased(P<0.05). Compared with the model group, the symptoms of cold coagulation and blood stasis in each treatment group were improved, and the area of ectopic lesions was significantly reduced(P<0.05 or P<0.01). The mRNA and protein expression levels of CHCHD4 and HIF-1α were significantly decreased(P<0.05 or P<0.01). In the cell model, compared with the control group, the expression of CHCHD4, HIF-1α protein, glucose consumption, lactic acid level, and cell proliferation activity in the CHCHD4 overexpression group were significantly increased(P<0.01). Compared with the CHCHD4 overexpression group, there was no significant change in each index in the control serum group, while the protein expression of CHCHD4 and HIF-1α in the Liangfang Wenjing Decoction serum group was decreased significantly(P<0.05 or P<0.01). The glucose consumption, lactic acid level, and cell proliferation activity decreased significantly(P<0.01). It can be seen from the above that the therapeutic effect of Liangfang Wenjing Decoction on EMs with cold coagulation and blood stasis might be related to reducing the expression of CHCHD4 and then improving the hypoxia of ectopic lesions and ectopic ESCs.

[Development and Validation of a Risk Prediction Model for Prolonged Hospitalization in Patients With Diabetic Foot Ulcers]. / ç³–å°¿ç— è¶³æºƒç–¡æ‚£è€ ä½é™¢æ—¶é—´å»¶é•¿é£Žé™©é¢„æµ‹æ¨¡åž‹æž„å»ºåŠéªŒè¯.

Objective: To investigate the risk factors associated with prolonged hospitalization in patients diagnosed with diabetic foot ulcers (DFU), to develop a predictive model, and to conduct internal validation of the model. Methods: The clinical data of DFU patients admitted to West China Hospital, Sichuan University between January 2012 and December 2022 were retrospectively collected. The subjects were randomly assigned to a training cohort and a validation cohort at a ratio of 7 to 3. Hospital stays longer than 75th percentile were defined as prolonged length-of-stay. A thorough analysis of the risk factors was conducted using the training cohort, which enabled the development of an accurate risk prediction model. To ensure robustness, the model was internally validated using the validation cohort. Results: A total of 967 inpatients with DFU were included, among whom 245 patients were identified as having an extended length-of-stay. The training cohort consisted of 622 patients, while the validation cohort comprised 291 patients. Multivariate logistic regression analysis revealed that smoking history (odds ratio [OR]=1.67, 95% confidence interval [CI], 1.13 to 2.48, P=0.010), Wagner grade 3 or higher (OR=7.13, 95% CI, 3.68 to 13.83, P<0.001), midfoot ulcers (OR=1.99, 95% CI, 1.07 to 3.72, P=0.030), posterior foot ulcers (OR=3.68, 95% CI, 1.83 to 7.41, P<0.001), multisite ulcers (OR=2.91, 95% CI, 1.80 to 4.69, P<0.001), wound size≥3 cm2 (OR=2.00, 95% CI, 1.28-3.11, P=0.002), and white blood cell count (OR=1.11, 95% CI, 1.05 to 1.18, P<0.001) were associated with an increased risk of prolonged length of stay. Additionally, a nomogram was constructed based on the identified risk factors. The areas under the receiver operating characteristic (ROC) curves for both the training cohort and the validation cohort were 0.782 (95% CI, 0.745 to 0.820) and 0.756 (95% CI, 0.694 to 0.818), respectively, indicating robust predictive performance. Furthermore, the calibration plot demonstrated optimal concordance between the predicted probabilities and the observed outcomes in both the training and the validation cohorts. Conclusion: Smoking history, Wagner grade≥3, midfoot ulcers, posterior foot ulcers, multisite ulcers, ulcer area≥3 cm2, and elevated white blood cell count are identified as independent predictors of prolonged hospitalization. Therefore, it is imperative that clinicians conduct a comprehensive patient evaluation and implement appropriate diagnostic and therapeutic strategies to effectively shorten the length of stay for DFU patients.

Diagnostic value of CEUS combined with C-TIRADS for indeterminate FNA cytological thyroid nodules.

OBJECTIVES: To investigate the diagnostic value of CEUS combined with C-TIRADS for indeterminate FNA cytological thyroid nodules. METHODS: The clinical data, ultrasonic images, C-TIRADS categories and CEUS images of 192 patients with indeterminate FNA cytological thyroid nodules confirmed by the surgical pathology were analyzed retrospectively. The diagnostic efficacy of CEUS, C-TIRADS and CEUS-TIRADS were calculated. RESULTS: The AUCs of CEUS, C-TIRADS and CEUS-TIRADS were 0.905 (95% CI: 0.862∼0.949), 0.881 (95% CI: 0.825∼0.938) and 0.954 (95% CI: 0.922∼0.986), respectively. The sensitivity, specificity, PPV, NPV, accuracy, LR- and LR+ were 84.7% (116/137), 85.5% (47/55), 93.5% (116/124), 69.1% (47/68), 84.9% (163/192), 0.179, 5.82 and 84.7% (116/137), 83.6% (46/55), 92.8% (116/125), 68.7% (46/67), 84.4% (162/192), 0.183, 5.17, 92.7% (127/137), 89.1% (49/55), 95.5% (127/133), 83.1% (49/59), 91.7% (176/192), 0.082, and 8.50, respectively. Compared with CEUS and C-TIRADS, CEUS-TIRADS had improved the AUC, sensitivity and accuracy (all P < 0.05). CONCLUSIONS: CEUS and C-TIRADS had high diagnostic values in indeterminate FNA cytological thyroid nodules. CEUS-TIRADS improved AUC, diagnostic sensitivity and accuracy, and helped to distinguish indeterminate FNA cytological nodules.

Association of peripheral eosinophil count with chronic kidney disease progression risk: a retrospective cohort study in Chinese population.

BACKGROUND: The role of peripheral eosinophils in chronic kidney disease (CKD) requires further evaluation. We aimed to determine whether an eosinophil count increase is related to the occurrence of end-stage renal disease (ESRD). METHODS: This single-center, observational, retrospective cohort study was conducted between January 2016 and December 2018 in Hangzhou, China, and included 3163 patients, categorized into four groups according to peripheral eosinophil count (PEC) quartile values. The main outcome was ESRD development during follow-up. We evaluated the relationship between the serum eosinophil count, demographic and clinical information, and ESRD incidence. Cox proportional hazards models and Kaplan-Meier survival curves were used. RESULTS: A total of 3163 patients with CKD were included in this cohort, of whom 1254 (39.6%) were females. The median (interquartile range [IQR]) age was 75 [64, 85] years, and the median (IQR) estimated glomerular filtration rate was 55.16 [45.19, 61.19] mL/min/1.73 m2. The median PEC was 0.1224 × 109/L (IQR, 0.0625-0.212). Among the 3163 patients with CKD, 273 (8.6%) developed ESRD during a median follow-up time of 443.8 [238.8, 764.9] days. Individuals in the highest PEC quartile had a 66.2% higher ESRD risk than those in the lowest quartile (hazard ratio, 1.662; 95% confidence interval, 1.165-2.372). The results from the Kaplan-Meier survival curves confirmed the conclusion. CONCLUSIONS: Alongside traditional risk factors, patients with CKD and an elevated PEC are more likely to develop ESRD. Therefore, more attention should be paid to those patients with CKD who have a high PEC.

Causal relationship between OHSS and immune cells: A Mendelian randomization study.

OBJECTIVE: To confirm the causal relationship between immune cells and Ovarian Hyperstimulation Syndrome. DESIGN: Obtaining data, collecting single nucleotide polymorphisms, detecting instrumental variables heterogeneity, assessing causality, and assessing bidirectional causality. SUBJECTS: A two sample Mendelian study to confirm the causal relationship between immune cells and Ovarian Hyperstimulation Syndrome. EXPOSURE: Immune cell phenotype (including 22 million SNPs from GWAS on 3757 European individuals). MAIN OUTCOME MEASURES: Inverse variance weighting, one-sample analysis, MR-Egger, weighted median and weighted mode are used to assess the causal relationship between 731 immunophenotypes and Ovarian Hyperstimulation Syndrome. The weighted median and Mendelian Randomization multi-effect residuals and Mendelian Randomization multi-effect residuals and outlier tests are used to assess bidirectional causality between this two. RESULTS: After False Discovery Rate correction, 9 immunophenotypes were found to be significantly associated with the risk of Ovarian Hyperstimulation Syndrome. B cell panel: IgD+ AC (OR, 0.90) 、CD19 on CD24+ CD27+ (OR, 0.86) 、BAFF-R on CD20- CD38 (OR, -1.22); Mature T cell group panel: EM DN (CD4 -CD8-) AC (OR, 1.46); Myeloid cell panel: Mo MDSC AC (OR, 1.13) 、CD45 on CD33br HLA-DR+ (OR, 0.87); Monocyte panel: HLA-DR on monocyte (OR, 0.86) 、CCR2 on CD14+ CD16+ monocyte (OR, 1.15) 、cDC panel: HLA-DR on myeloid DC (OR, 0.89). CONCLUSION: This study shows the potential link between OHSS and immune cells by genetic means, providing new ideas for future clinical and basic research.

Medium-Chain Chlorinated Paraffins Trigger Thyroid Hormone Synthesis and Interfere with Mitochondrial Function in the Thyroid Gland.

Medium-chain chlorinated paraffins (MCCPs, C14-C17) are frequently detected in diverse environmental media. It has been proposed to be listed in Annex A of the Convention on Persistent Organic Pollutants in 2023. Although MCCPs are a crucial health concern, their toxicity remains unclear. This study investigated the toxic effects of MCCPs (0.1-50 mg/kg body weight/day) on the thyroid gland of female Sprague-Dawley rats and characterized the potential toxic pathways via transcriptomics and metabolomics approaches. MCCPs exposure caused histopathological changes to the endoplasmic reticula and mitochondria in thyroid follicular cells at a dose of 50 mg/kg bw/d and increased serum thyrotropin-releasing hormone, thyroid-stimulating hormones, and thyroxine when exposed to a higher dose of MCCPs. Transcriptomic analysis indicated the excessive expression of key genes related to thyroid hormone synthesis induced by MCCPs. Integrating the dual-omics analysis revealed mitochondrial dysfunction of the thyroid by mediating fatty acid oxidation, Kreb's cycle, and oxidative phosphorylation. Significant metabolic toxicity on the thyroid might be linked to the characteristics of the chlorine content of MCCPs. This study revealed the toxicity of MCCPs to the thyroid gland via triggering thyroid hormone synthesis and interfering with mitochondrial function, which can provide new insights into the modes of action and mechanism-based risk assessment of MCCPs.

Identification of stripe rust resistance gene YrBDT in Chinese landrace wheat Baidatou using BSE-seq and BSR-seq.

KEY MESSAGE: A new stripe rust resistance gene YrBDT in Chinese landrace wheat Baidatou was mapped to a 943.6-kb interval on chromosome arm 6DS and co-segregated with a marker CAPS3 developed from candidate gene TraesCS6D03G0027300. Stripe rust caused by Puccinia striiformis f. sp. tritici (Pst) is a devastating foliar disease of wheat. Chinese landrace wheat Baidatou has shown high resistance to a broad spectrum of Pst races at both the seedling and adult-plant stages for decades in the Longnan region of Gansu province, a hot spot for stripe rust epidemics. Here, we report fine mapping and candidate gene analysis of stripe rust resistance gene YrBDT in Baidatou. Analysis of F1, F2 plants and F2:3 lines indicated that resistance in Baidatou to Pst race CYR31 was conferred by a single dominant gene, temporarily designated YrBDT. Bulked segregant exome capture sequencing (BSE-seq) analysis revealed 61 high-confidence polymorphic SNPs concentrated in a 5.4-Mb interval at the distal of chromosome arm 6DS. Several SNPs and InDels were also identified by genome mining of DNA sampled from the parents and contrasting bulks. The YrBDT locus was mapped to a 943.6-kb (4,658,322-5,601,880 bp) genomic region spanned by markers STS2 and STS3 based on IWGSC RefSeq v2.1, including five putative disease resistance genes. There was high collinearity of the target interval among Chinese Spring RefSeq v2.1, Ae. tauschii AL8/78 and Fielder genomes. The expression level of TraesCS6D03G0027300 showed significant association with Pst infection, and a gene-specific marker CAPS3 developed from TraesCS6D03G0027300 co-segregated with YrBDT suggesting this gene as a candidate of YrBDT. The resistance gene and flanking markers can be used in marker-assisted selection for improvement of stripe rust resistance.

A radiomics approach for predicting gait freezing in Parkinson's disease based on resting-state functional magnetic resonance imaging indices: a cross-sectional study.

Freezing of gait is a significant and debilitating motor symptom often observed in individuals with Parkinson's disease. Resting-state functional magnetic resonance imaging, along with its multi-level feature indices, has provided a fresh perspective and valuable insight into the study of freezing of gait in Parkinson's disease. It has been revealed that Parkinson's disease is accompanied by widespread irregularities in inherent brain network activity. However, the effective integration of the multi-level indices of resting-state functional magnetic resonance imaging into clinical settings for the diagnosis of freezing of gait in Parkinson's disease remains a challenge. Although previous studies have demonstrated that radiomics can extract optimal features as biomarkers to identify or predict diseases, a knowledge gap still exists in the field of freezing of gait in Parkinson's disease. This cross-sectional study aimed to evaluate the ability of radiomics features based on multi-level indices of resting-state functional magnetic resonance imaging, along with clinical features, to distinguish between Parkinson's disease patients with and without freezing of gait. We recruited 28 patients with Parkinson's disease who had freezing of gait (15 men and 13 women, average age 63 years) and 30 patients with Parkinson's disease who had no freezing of gait (16 men and 14 women, average age 64 years). Magnetic resonance imaging scans were obtained using a 3.0T scanner to extract the mean amplitude of low-frequency fluctuations, mean regional homogeneity, and degree centrality. Neurological and clinical characteristics were also evaluated. We used the least absolute shrinkage and selection operator algorithm to extract features and established feedforward neural network models based solely on resting-state functional magnetic resonance imaging indicators. We then performed predictive analysis of three distinct groups based on resting-state functional magnetic resonance imaging indicators indicators combined with clinical features. Subsequently, we conducted 100 additional five-fold cross-validations to determine the most effective model for each classification task and evaluated the performance of the model using the area under the receiver operating characteristic curve. The results showed that when differentiating patients with Parkinson's disease who had freezing of gait from those who did not have freezing of gait, or from healthy controls, the models using only the mean regional homogeneity values achieved the highest area under the receiver operating characteristic curve values of 0.750 (with an accuracy of 70.9%) and 0.759 (with an accuracy of 65.3%), respectively. When classifying patients with Parkinson's disease who had freezing of gait from those who had no freezing of gait, the model using the mean amplitude of low-frequency fluctuation values combined with two clinical features achieved the highest area under the receiver operating characteristic curve of 0.847 (with an accuracy of 74.3%). The most significant features for patients with Parkinson's disease who had freezing of gait were amplitude of low-frequency fluctuation alterations in the left parahippocampal gyrus and two clinical characteristics: Montreal Cognitive Assessment and Hamilton Depression Scale scores. Our findings suggest that radiomics features derived from resting-state functional magnetic resonance imaging indices and clinical information can serve as valuable indices for the identification of freezing of gait in Parkinson's disease.

Enzymatic Stoichiometry Reveals the Metabolic Limitations of Soil Microbes under Nitrogen and Phosphorus Addition in Chinese Fir Plantations.

Increasing nitrogen (N) deposition alters the availability of soil nutrients and is likely to intensify phosphorus (P) limitations, especially in P-limited tropical and subtropical forests. Soil microorganisms play vital roles in carbon (C) and nutrient cycling, but it is unclear whether and how much N and P imbalances affect the soil's microbial metabolism and mechanisms of nutrient limitations. In this study, a 3-year field experiment of N and P addition (control (CK), 100 kg N ha-1 yr-1 (N), 50 kg P ha-1 yr-1 (P), and NP) was set up to analyze the extracellular enzyme activities and stoichiometry characteristics of the top mineral soils in Chinese fir plantations with different stand ages (7, 20, and 33 years old). The results showed that the enzyme activities associated with the acquisition of C (ß-1,4-glucosidase (BG) and ß-d-cellobiohydrolase (CBH)) and P (acid phosphatases (APs)) in the N treatment were significantly higher than those in the CK treatment. Moreover, vector analysis revealed that both the vector's length and angle increased in stands of all ages, which indicated that N addition aggravated microbial C and P limitations. The P and NP treatments both significantly decreased the activity of AP and the enzymes' N:P ratio, thereby alleviating microbial P limitations, as revealed by the reduction in the vector's angle. Stand age was found to promote all enzymatic activities but had no obvious effects on the limitation of microbial metabolism with or without added nutrients in the soils under Chinese fir. Available N, Olsen-P, and pH were the main drivers of microbial metabolic limitations related to C nutrients. These results provide useful data for understanding the change in soil microbial activity in response to environmental changes, and suggest that P fertilization should be considered for management to improve productivity and C sequestration in Chinese fir plantation in the context of increased deposition of N.

mRNA Profiling and Transcriptomics Analysis of Chickens Received Newcastle Disease Virus Genotype II and Genotype VII Vaccines.

Newcastle Disease Virus (NDV) genotype VII (GVII) is becoming the predominant strain of NDV in the poultry industry. It causes high mortality even in vaccinated chickens with a common NDV genotype II vaccine (GII-vacc). To overcome this, the killed GVII vaccine has been used to prevent NDV outbreaks. However, the debate about vaccine differences remains ongoing. Hence, this study investigated the difference in chickens' responses to the two vaccines at the molecular level. The spleen transcriptomes from vaccinated chickens reveal that GVII-vacc affected the immune response by downregulating neuroinflammation. It also enhanced a synaptogenesis pathway that operates typically in the nervous system, suggesting a mechanism for the neurotrophic effect of this strain. We speculated that the down-regulated immune system regulation correlated with protecting the nervous system from excess leukocytes and cytokine activity. In contrast, GII-vacc inhibited apoptosis by downregulating PERK/ATF4/CHOP as part of the unfolded protein response pathway but did not affect the expression of the same synaptogenesis pathway. Thus, the application of GVII-vacc needs to be considered in countries where GVII is the leading cause of NDV outbreaks. The predicted molecular signatures may also be used in developing new vaccines that trigger specific genes in the immune system in combating NDV outbreaks.

Multi-parametric MRI-based machine learning model for prediction of pathological grade of renal injury in a rat kidney cold ischemia-reperfusion injury model.

BACKGROUND: Renal cold ischemia-reperfusion injury (CIRI), a pathological process during kidney transplantation, may result in delayed graft function and negatively impact graft survival and function. There is a lack of an accurate and non-invasive tool for evaluating the degree of CIRI. Multi-parametric MRI has been widely used to detect and evaluate kidney injury. The machine learning algorithms introduced the opportunity to combine biomarkers from different MRI metrics into a single classifier. OBJECTIVE: To evaluate the performance of multi-parametric magnetic resonance imaging for grading renal injury in a rat model of renal cold ischemia-reperfusion injury using a machine learning approach. METHODS: Eighty male SD rats were selected to establish a renal cold ischemia -reperfusion model, and all performed multiparametric MRI scans (DWI, IVIM, DKI, BOLD, T1mapping and ASL), followed by pathological analysis. A total of 25 parameters of renal cortex and medulla were analyzed as features. The pathology scores were divided into 3 groups using K-means clustering method. Lasso regression was applied for the initial selecting of features. The optimal features and the best techniques for pathological grading were obtained. Multiple classifiers were used to construct models to evaluate the predictive value for pathology grading. RESULTS: All rats were categorized into mild, moderate, and severe injury group according the pathologic scores. The 8 features that correlated better with the pathologic classification were medullary and cortical Dp, cortical T2*, cortical Fp, medullary T2*, ∆T1, cortical RBF, medullary T1. The accuracy(0.83, 0.850, 0.81, respectively) and AUC (0.95, 0.93, 0.90, respectively) for pathologic classification of the logistic regression, SVM, and RF are significantly higher than other classifiers. For the logistic model and combining logistic, RF and SVM model of different techniques for pathology grading, the stable and perform are both well. Based on logistic regression, IVIM has the highest AUC (0.93) for pathological grading, followed by BOLD(0.90). CONCLUSION: The multi-parametric MRI-based machine learning model could be valuable for noninvasive assessment of the degree of renal injury.

Deep learning for intracranial aneurysm segmentation using CT angiography.

Objective.This study aimed to employ a two-stage deep learning method to accurately detect small aneurysms (4-10 mm in size) in computed tomography angiography images.Approach.This study included 956 patients from 6 hospitals and a public dataset obtained with 6 CT scanners from different manufacturers. The proposed method consists of two components: a lightweight and fast head region selection (HRS) algorithm and an adaptive 3D nnU-Net network, which is used as the main architecture for segmenting aneurysms. Segments generated by the deep neural network were compared with expert-generated manual segmentation results and assessed using Dice scores.MainResults.The area under the curve (AUC) exceeded 79% across all datasets. In particular, the precision and AUC reached 85.2% and 87.6%, respectively, on certain datasets. The experimental results demonstrated the promising performance of this approach, which reduced the inference time by more than 50% compared to direct inference without HRS.Significance.Compared with a model without HRS, the deep learning approach we developed can accurately segment aneurysms by automatically localizing brain regions and can accelerate aneurysm inference by more than 50%.

Genetically predicted 1091 blood metabolites and 309 metabolite ratios in relation to risk of type 2 diabetes: a Mendelian randomization study.

Background: Metabolic dysregulation represents a defining characteristic of Type 2 diabetes (T2DM). Nevertheless, there remains an absence of substantial evidence establishing a direct causal link between circulating blood metabolites and the promotion or prevention of T2DM. In addressing this gap, we employed Mendelian randomization (MR) analysis to investigate the potential causal association between 1,091 blood metabolites, 309 metabolite ratios, and the occurrence of T2DM. Methods: Data encompassing single-nucleotide polymorphisms (SNPs) for 1,091 blood metabolites and 309 metabolite ratios were extracted from a Canadian Genome-wide association study (GWAS) involving 8,299 participants. To evaluate the causal link between these metabolites and Type 2 diabetes (T2DM), multiple methods including Inverse Variance Weighted (IVW), Weighted Median, MR Egger, Weighted Mode, and Simple Mode were employed. p-values underwent correction utilizing False Discovery Rates (FDR). Sensitivity analyses incorporated Cochran's Q test, MR-Egger intercept test, MR-PRESSO, Steiger test, leave-one-out analysis, and single SNP analysis. The causal effects were visualized via Circos plot, forest plot, and scatter plot. Furthermore, for noteworthy, an independent T2DM GWAS dataset (GCST006867) was utilized for replication analysis. Metabolic pathway analysis of closely correlated metabolites was conducted using MetaboAnalyst 5.0. Results: The IVW analysis method utilized in this study revealed 88 blood metabolites and 37 metabolite ratios demonstrating a significant causal relationship with T2DM (p < 0.05). Notably, strong causal associations with T2DM were observed for specific metabolites: 1-linoleoyl-GPE (18:2) (IVW: OR:0.930, 95% CI: 0.899-0.962, p = 2.16 × 10-5), 1,2-dilinoleoyl-GPE (18:2/18:2) (IVW: OR:0.942, 95% CI: 0.917-0.968, p = 1.64 × 10-5), Mannose (IVW: OR:1.133, 95% CI: 1.072-1.197, p = 1.02 × 10-5), X-21829 (IVW: OR:1.036, 95% CI: 1.036-1.122, p = 9.44 × 10-5), and Phosphate to mannose ratio (IVW: OR:0.870, 95% CI: 0.818-0.926, p = 1.29 × 10-5, FDR = 0.008). Additionally, metabolic pathway analysis highlighted six significant pathways associated with T2DM development: Valine, leucine and isoleucine biosynthesis, Phenylalanine metabolism, Glycerophospholipid metabolism, Alpha-Linolenic acid metabolism, Sphingolipid metabolism, and Alanine, aspartate, and glutamate metabolism. Conclusion: This study identifies both protective and risk-associated metabolites that play a causal role in the development of T2DM. By integrating genomics and metabolomics, it presents novel insights into the pathogenesis of T2DM. These findings hold potential implications for early screening, preventive measures, and treatment strategies for T2DM.

Bacterial composition and physicochemical characteristics of sorghum based on environmental factors in different regions of China.

The fermentation process for Jiang-flavored baijiu using sorghum as the raw material involves a variety of microorganisms. However, the specific physicochemical characteristics of sorghum and microbial composition on its surface have not been fully elucidated. We aimed to perform a comprehensive comparative analysis of the variations in physicochemical properties and surface microflora in waxy sorghum samples from three prominent production regions in China (Renhuai, Jinsha, and Duyun). Multivariate statistical assessments were conducted that incorporated local soil and climate variables. The results showed that Cyanobacteria, unclassified bacteria, Proteobacteria, Firmicutes, and Bacteroidota were the dominant bacteria in these regions. These bacteria were associated with ethyl acetate, ethyl caprylate, ethyl lactate, and butyl groups, which synergistically produce flavorful compounds. The surface bacterial communities were affected by soil total phosphorus, altitude, diurnal temperature range, monthly mean temperature, precipitation, and effective accumulated temperature. The findings of this study provide a new perspective on microorganisms related to Jiang-flavored baijiu and can help establish a reference for the stability of liquor quality.