One-Pot Synthesis of 4-Chloroquinolines via Bis(trichloromethyl) Carbonate and Triphenylphosphine Oxide-Mediated Cascade Reactions of N-Aryl Enaminones.

A novel method for synthesizing substituted 4-chloroquinolines has been devised, utilizing a cascade reaction of N-aryl enaminones promoted by bis(trichloromethyl) carbonate (BTC) and triphenylphosphine oxide (TPPO). This approach features accessible starting materials, a broad substrate range, extensive functional group compatibility, gentle reaction conditions, and straightforward operation. Its versatility is evidenced by its facile scalability and suitability for late-stage derivatization. A plausible mechanism involving α-carbonylation, 6π-azaelectrocyclization, and dehydroxychlorination sequence is proposed.

[Interaction Effects of Vegetation and Soil Factors on Microbial Communities in Alpine Steppe Under Degradation].

To clarify the regulating effect of vegetation and soil factors on microbial communities in the alpine steppe under degradation on the Qinghai-Xizang Plateau, the alpine steppe in the Sanjiangyuan area of the Qinghai-Tibet Plateau was chosen. We analyzed the differences in vegetation and soil factors in different stages of degradation （non-degradation, moderate degradation, and severe degradation） and detected the variations in microbial community characteristics in the alpine steppe under different degradation stages using high-throughput sequencing technology. Eventually, redundancy analysis （RDA） and multiple regression matrixes （MRM） based on the similarity or dissimilarity matrix were used to identify key environmental factors regulating microbial （bacterial and fungal） community changes under degradation. The results showed that the degradation of the alpine steppe significantly changed the community coverage, height, biomass, and important value of graminae； significantly reduced the contents of soil organic matter, total nitrogen, total phosphorus, and silt； and increased the soil bulk density and sand content. Degradation did not change the composition of bacteria and fungi, but their composition proportions changed and also resulted in the loss of microbial richness （Chao1 index and Richness index） but did not significantly change the microbial diversity （Shannon index）. With the occurrence of degradation, the vegetation characteristics, soil physicochemical properties, and microbial diversity showed a consistent change trend. Combined with the characteristics of the network topology changes （the number of nodes and clustering coefficient significantly decreased）, it was found that degradation of the alpine steppe led to the decline of interspecies interactions, decentralization of network, and homogenization of microorganisms, but the cooperation relations among the species were maintained （positive correlation connections accounted for more than 90% in all degradation stages）. Under the alpine steppe degradation, the vegetation-soil interaction had the greatest effect on soil bacterial community, whereas soil physicochemical properties had the greatest influence on soil fungal community. Specifically, vegetation community height, biomass, and soil bulk density were the mutual factors regulating soil microorganisms, whereas the vegetation Simpson index, important value of graminae, soil total phosphorus, total potassium, and silt content were the unique factors affecting the soil bacterial community, and soil pH and total nitrogen content were the particular factors affecting the soil fungal community.

Bidirectional regulation mechanism of TRPM2 channel: role in oxidative stress, inflammation and ischemia-reperfusion injury.

Transient receptor potential melastatin 2 (TRPM2) is a non-selective cation channel that exhibits Ca2+ permeability. The TRPM2 channel is expressed in various tissues and cells and can be activated by multiple factors, including endogenous ligands, Ca2+, reactive oxygen species (ROS) and temperature. This article reviews the multiple roles of the TRPM2 channel in physiological and pathological processes, particularly on oxidative stress, inflammation and ischemia-reperfusion (I/R) injury. In oxidative stress, the excessive influx of Ca2+ caused by the activation of the TRPM2 channel may exacerbate cellular damage. However, under specific conditions, activating the TRPM2 channel can have a protective effect on cells. In inflammation, the activation of the TRPM2 channel may not only promote inflammatory response but also inhibit inflammation by regulating ROS production and bactericidal ability of macrophages and neutrophils. In I/R, the activation of the TRPM2 channel may worsen I/R injury to various organs, including the brain, heart, kidney and liver. However, activating the TRPM2 channel may protect the myocardium from I/R injury by regulating calcium influx and phosphorylating proline-rich tyrosine kinase 2 (Pyk2). A thorough investigation of the bidirectional role and regulatory mechanism of the TRPM2 channel in these physiological and pathological processes will aid in identifying new targets and strategies for treatment of related diseases.

Investigating the role of killer cell immunoglobulin-like receptors and human leukocyte antigen genetic variants in hepatitis C virus infection.

The genetic diversity of killer cell immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) genes influences the host's immune response to viral pathogens. This study aims to explore the impact of five single nucleotide polymorphisms (SNPs) in KIR3DL2 and HLA-A genes on hepatitis C virus (HCV) infection. A total of 2251 individuals were included in the case-control study. SNPs including KIR3DL2 rs11672983, rs3745902, rs1654644, and HLA-A rs3869062, rs12202296 were genotyped. By controlling various confounding factors using a modified logistic regression model, as well as incorporating stratified analysis, joint effects analysis, and multidimensional bioinformatics analysis, we analyzed the relationship between SNPs and HCV infection. The logistic regression analysis showed a correlation between KIR3DL2 rs11672983 AA, KIR3DL2 rs3745902 TT, and increased HCV susceptibility (p < 0.01). Stratified analysis indicated that KIR3DL2 rs1654644 and HLA-A rs3869062 also heightened HCV susceptibility in certain subgroups. A linear trend of rising HCV infection rates was observed when combining KIR3DL2 rs11672983 AA and KIR3DL2 rs3745902 TT (ptrend = 0.007). Bioinformatics analysis suggested these SNPs' regulatory potential and their role in altering messenger RNA secondary structure, implying their functional relevance in HCV susceptibility. Our findings indicate that KIR3DL2 rs11672983 AA and KIR3DL2 rs3745902 TT are significantly associated with increased susceptibility to HCV infection.

Targeting ROS in cancer: rationale and strategies.

Reactive oxygen species (ROS) in biological systems are transient but essential molecules that are generated and eliminated by a complex set of delicately balanced molecular machineries. Disruption of redox homeostasis has been associated with various human diseases, especially cancer, in which increased ROS levels are thought to have a major role in tumour development and progression. As such, modulation of cellular redox status by targeting ROS and their regulatory machineries is considered a promising therapeutic strategy for cancer treatment. Recently, there has been major progress in this field, including the discovery of novel redox signalling pathways that affect the metabolism of tumour cells as well as immune cells in the tumour microenvironment, and the intriguing ROS regulation of biomolecular phase separation. Progress has also been made in exploring redox regulation in cancer stem cells, the role of ROS in determining cell fate and new anticancer agents that target ROS. This Review discusses these research developments and their implications for cancer therapy and drug discovery, as well as emerging concepts, paradoxes and future perspectives.

The Association Between Tumor Radiomic Analysis and Peritumor Habitat-Derived Radiomic Analysis on Gadoxetate Disodium-Enhanced MRI With Microvascular Invasion in Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) has a poor prognosis, often characterized by microvascular invasion (MVI). Radiomics and habitat imaging offer potential for preoperative MVI assessment. PURPOSE: To identify MVI in HCC by habitat imaging, tumor radiomic analysis, and peritumor habitat-derived radiomic analysis. STUDY TYPE: Retrospective. SUBJECTS: Three hundred eighteen patients (53 ± 11.42 years old; male = 276) with pathologically confirmed HCC (training:testing = 224:94). FIELD STRENGTH/SEQUENCE: 1.5 T, T2WI (spin echo), and precontrast and dynamic T1WI using three-dimensional gradient echo sequence. ASSESSMENT: Clinical model, habitat model, single sequence radiomic models, the peritumor habitat-derived radiomic model, and the combined models were constructed for evaluating MVI. Follow-up clinical data were obtained by a review of medical records or telephone interviews. STATISTICAL TESTS: Univariable and multivariable logistic regression, receiver operating characteristic (ROC) curve, calibration, decision curve, Delong test, K-M curves, log rank test. A P-value less than 0.05 (two sides) was considered to indicate statistical significance. RESULTS: Habitat imaging revealed a positive correlation between the number of subregions and MVI probability. The Radiomic-Pre model demonstrated AUCs of 0.815 (95% CI: 0.752-0.878) and 0.708 (95% CI: 0.599-0.817) for detecting MVI in the training and testing cohorts, respectively. Similarly, the AUCs for MVI detection using Radiomic-HBP were 0.790 (95% CI: 0.724-0.855) for the training cohort and 0.712 (95% CI: 0.604-0.820) for the test cohort. Combination models exhibited improved performance, with the Radiomics + Habitat + Dilation + Habitat 2 + Clinical Model (Model 7) achieving the higher AUC than Model 1-4 and 6 (0.825 vs. 0.688, 0.726, 0.785, 0.757, 0.804, P = 0.013, 0.048, 0.035, 0.041, 0.039, respectively) in the testing cohort. High-risk patients (cutoff value >0.11) identified by this model showed shorter recurrence-free survival. DATA CONCLUSION: The combined model including tumor size, habitat imaging, radiomic analysis exhibited the best performance in predicting MVI, while also assessing prognostic risk. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Efficacy and safety of multikinase inhibitors for patients with refractory thyroid cancer: Systematic review and network meta-analysis.

CONTEXT: Multikinase inhibitors (MKIs) improve the treatment of refractory thyroid cancer, included radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC) and advanced medullary thyroid carcinoma (aMTC). OBJECTIVE: This study aims to compare the efficacy of MKIs in improving survival outcomes and safety. DATA SOURCES: Comprehensive database searches of MEDLINE via PubMed, EMBASE and Cochrane performed from inception to December 2023. STUDY SELECTION: Three independent authors selected these studies. Randomised-controlled trials that compared the use of a MKI to other MKIs or placebo were included. DATA EXTRACTION AND SYNTHESIS: This review followed PRISMA guidelines. Risk of bias was analyzed using the Cochrane RoB 2 tool. Bayesian network meta-analysis was performed. Treatments were grouped into common nodes based on the type of MKI. MAIN OUTCOMES AND MEASURES: Primary outcomes were progression-free survival (PFS) and overall survival (OS). Secondary outcomes included objective response rate, disease control rate, clinical benefit rate, and adverse events. RESULTS: Cabozantinib 60 mg/d (CAB60) was associated with the highest prolonged PFS in RAIR-DTC patients, followed by lentivatinib 18 or 24 mg/d (LEN18 or LEN24), and apatinib. PFS was also improved in in aMTC patients received CAB 140 mg/d (CAB140), CAB60, or anlotinib. A significantly greater improvement on the performance of OS was seen in CAB60, LEN24, anlotinib, and sorafenib in RAIR-DTC patients, but which in aMTC patients were lack of statistical differences. Compared with the low-dose of MKIs, high-dose of MKIs such as CAB, LEN, and vandetanib increased the incidence of adverse events. CONCLUSION: CAB60, LEN, and apatinib are promising topical MKIs with statistically significant primary outcomes in RAIR-DTC patients, while CAB and anlotinib are effective in prolonging PFS in aMTC patients.

MR radiomics to predict microvascular invasion status and biological process in combined hepatocellular carcinoma-cholangiocarcinoma.

OBJECTIVES: To establish an MRI-based radiomics model for predicting the microvascular invasion (MVI) status of cHCC-CCA and to investigate biological processes underlying the radiomics model. METHODS: The study consisted of a retrospective dataset (82 in the training set, 36 in the validation set) and a prospective dataset (25 patients in the test set) from two hospitals. Based on the training set, logistic regression analyses were employed to develop the clinical-imaging model, while radiomic features were extracted to construct a radiomics model. The diagnosis performance was further validated in the validation and test sets. Prognostic aspects of the radiomics model were investigated using the Kaplan-Meier method and log-rank test. Differential gene expression analysis and gene ontology (GO) analysis were conducted to explore biological processes underlying the radiomics model based on RNA sequencing data. RESULTS: One hundred forty-three patients (mean age, 56.4 ± 10.5; 114 men) were enrolled, in which 73 (51.0%) were confirmed as MVI-positive. The radiomics model exhibited good performance in predicting MVI status, with the area under the curve of 0.935, 0.873, and 0.779 in training, validation, and test sets, respectively. Overall survival (OS) was significantly different between the predicted MVI-negative and MVI-positive groups (median OS: 25 vs 18 months, p = 0.008). Radiogenomic analysis revealed associations between the radiomics model and biological processes involved in regulating the immune response. CONCLUSION: A robust MRI-based radiomics model was established for predicting MVI status in cHCC-CCA, in which potential prognostic value and underlying biological processes that regulate immune response were demonstrated. CRITICAL RELEVANCE STATEMENT: MVI is a significant manifestation of tumor invasiveness, and the MR-based radiomics model established in our study will facilitate risk stratification. Furthermore, underlying biological processes demonstrated in the radiomics model will offer valuable insights for guiding immunotherapy strategies. KEY POINTS: MVI is of prognostic significance in cHCC-CCA, but lacks reliable preoperative assessment. The MRI-based radiomics model predicts MVI status effectively in cHCC-CCA. The MRI-based radiomics model demonstrated prognostic value and underlying biological processes. The radiomics model could guide immunotherapy and risk stratification in cHCC-CCA.

The causal effect of atopic dermatitis on lung cancer: A Mendelian randomization study.

BACKGROUND: Growing evidence has shown that atopic dermatitis (AD) may decrease lung cancer (LC) risk. However, the causality between the two diseases is inconsistent and controversial. Therefore, we explored the causal relationship between AD and different histological subtypes of LC by using the Mendelian randomization (MR) method. MATERIALS AND METHODS: We conducted the MR study based on summary statistics from the genome-wide association studies (GWAS) of AD (10,788 cases and 30,047 controls) and LC (29,266 cases and 56,450 controls). Instrumental variables (IVs) were obtained after removing SNPs associated with potential confounders. We employed inverse-variance weighted (IVW), MR-Egger, and weighted median methods to pool estimates, and performed a comprehensive sensitivity analysis. RESULTS: The results of the IVW method suggested that AD may decrease the risk of developing lung adenocarcinoma (LUAD) (OR = 0.91, 95% CI: 0.85-0.97, P = 0.007). Moreover, no causality was identified between AD and overall LC (OR = 0.96, 95% CI: 0.91-1.01, P = 0.101), lung squamous cell carcinoma (LUSC) (OR = 1.04, 95% CI: 0.96-1.036, P = 0.324), and small cell lung carcinoma (SCLC) (OR = 0.95, 95% CI: 0.82-1.10, P = 0.512). A comprehensive sensitivity test showed the robustness of our results. CONCLUSION: The present study indicates that AD may decrease the risk of LUAD in the European population, which needs additional investigations to identify the potential molecular mechanisms.

Biomimetic Mechanical Robust Cement-Resin Composites with Machine Learning-Assisted Gradient Hierarchical Structures.

Biological materials relying on hierarchically ordered architectures inspire the emergence of advanced composites with mutually exclusive mechanical properties, but the efficient topology optimization and large-scale manufacturing remain challenging. Herein, this work proposes a scalable bottom-up approach to fabricate a novel nacre-like cement-resin composite with gradient brick-and-mortar (BM) structure, and demonstrates a machine learning-assisted method to optimize the gradient structure. The fabricated gradient composite exhibits an extraordinary combination of high flexural strength, toughness, and impact resistance. Particularly, the toughness and impact resistance of such composite attractively surpass the cement counterparts by factors of approximately 700 and 600 times, and even outperform natural rocks, fiber-reinforced cement-based materials and even some alloys. The strengthening and toughening mechanisms are clarified as the regional-matrix densifying and crack-tip shielding effects caused by the gradient BM structure. The developed gradient composite not only endows a promising structural material for protective applications in harsh scenarios, but also paves a new way for biomimetic metamaterials designing.

Derivation of water quality criteria for paraquat, bisphenol A and carbamazepine using quantitative structure-activity relationship and species sensitivity distribution (QSAR-SSD).

The risk assessment of an expanding array of emerging contaminants in aquatic ecosystems and the establishment of water quality criteria rely on species sensitivity distribution (SSD), necessitating ample multi-trophic toxicity data. Computational methods, such as quantitative structure-activity relationship (QSAR), enable the prediction of specific toxicity data, thus mitigating the need for costly experimental testing and exposure risk assessment. In this study, robust QSAR models for four aquatic species (Rana pipiens, Crassostrea virginica, Asellus aquaticus, and Lepomis macrochirus) were developed using leave-one-out (LOO) screening variables and the partial least squares algorithm to predict toxicity data for paraquat, bisphenol A, and carbamazepine. These predicted data can be integrated with experimental data to construct SSD models and derive hazardous concentration for 5 % of species (HC5) for the criterion maximum concentration. The chronic water quality criterion for paraquat, bisphenol A, and carbamazepine were determined at 6.7, 11.1, and 3.5 µg/L, respectively. The QSAR-SSD approach presents a viable and cost-effective method for deriving water quality criteria for other emerging contaminants.

The diagnostic accuracy of infrared thermography in lumbosacral radicular pain: a prospective study.

BACKGROUND: To identify the sensitivity, specificity, and overall diagnostic accuracy of infrared thermography in diagnosing lumbosacral radicular pain. METHODS: Patients sequentially presenting with lower extremity pain were enrolled. A clinical certainty score ranging from 0 to 10 was used to assess the likelihood of lumbosacral radicular pain, with higher scores indicating higher likelihood. Infrared Thermography scans were performed and the temperature difference (ΔT) was calculated as ΔT = T1 - T2, where T2 represents the skin temperature of the most painful area on the affected limb and T1 represents the skin temperature of the same area on the unaffected limb. Upon discharge from the hospital, two independent doctors diagnosed lumbosacral radicular pain based on intraoperative findings, surgical effectiveness, and medical records. RESULTS: A total of 162 patients were included in the study, with the adjudicated golden standard diagnosis revealing that 101 (62%) patients had lumbosacral radicular pain, while the lower extremity pain in 61 patients was attributed to other diseases. The optimal diagnostic value for ΔT was identified to fall between 0.8℃ and 2.2℃, with a corresponding diagnostic accuracy, sensitivity, and specificity of 80%, 89%, and 66% respectively. The diagnostic accuracy, sensitivity, and specificity for the clinical certainty score were reported as 69%, 62%, and 79% respectively. Combining the clinical certainty score with ΔT yielded a diagnostic accuracy, sensitivity, and specificity of 84%, 77%, and 88% respectively. CONCLUSION: Infrared thermography proves to be a highly sensitive tool for diagnosing lumbosacral radicular pain. It offers additional diagnostic value in cases where general clinical evaluation may not provide conclusive results. TRIAL REGISTRATION: ChiCTR2300078786, 19/22/2023.

Association of Abdominal Aortic Calcification and Clinical Outcomes in LDH Patients Treated with Endoscopic Lumbar Discectomy.

INTRODUCTION: To determine any significant associations between abdominal aortic calcification (AAC) and clinical manifestations of pain symptoms following endoscopic lumbar discectomy. METHODS: Patients sequentially presenting with a history of unilateral radiculopathy with or without back pain, and with magnetic resonance imaging (MRI)-confirmed diagnosis of posterolateral disc herniation between August 2021 and December 2023 were eligible for inclusion in the study. All patients underwent endoscopic discectomy at our center during the study period. AAC stages were classified based on the Kauppila classification system using lateral lumbar radiographs. RESULTS: Between August 2021 and December 2023 a total of 120 patients were included in the study for analysis, of whom 82 (68.3%) exhibited mild AAC and 38 (31.7%) had moderate-severe AAC. Analyses using the multivariate linear regression model revealed a significant correlation between AAC comorbidity and postoperative clinical outcomes. At 1 year post-surgery, the mean change in leg pain following endoscopic lumbar discectomy was significantly less for patients with moderate-severe AAC (5.0 points) than for patients with mild ACC (p < 0.001). Even after adjusting for relevant confounders, this difference remained significant. Similar results were also observed in the postoperative improvement of back pain, the Oswestry Disability Index score, and the physical functioning, role physical, and bodily pain components of the 36-item Short Form Health Survey questionnaire. There was no significant difference in the rate of repeat surgery or post-surgical new-onset back pain between patients with different levels of severity of AAC at 1 year post-surgery. CONCLUSIONS: There is a significant association between the severity of AAC and clinical outcomes among patients with lumbar disk herniation who underwent endoscopic lumbar discectomy. AAC may serve as a prognostic factor in predicting surgical outcomes and guiding management strategies for patients with lumbar disk herniation following endoscopic lumbar discectomy.

Riluzole for Degenerative Cervical Myelopathy: A Secondary Analysis of the CSM-PROTECT Trial.

Importance: The modified Japanese Orthopaedic Association (mJOA) scale is the most common scale used to represent outcomes of degenerative cervical myelopathy (DCM); however, it lacks consideration for neck pain scores and neglects the multidimensional aspect of recovery after surgery. Objective: To use a global statistical approach that incorporates assessments of multiple outcomes to reassess the efficacy of riluzole in patients undergoing spinal surgery for DCM. Design, Setting, and Participants: This was a secondary analysis of prespecified secondary end points within the Efficacy of Riluzole in Surgical Treatment for Cervical Spondylotic Myelopathy (CSM-PROTECT) trial, a multicenter, double-blind, phase 3 randomized clinical trial conducted from January 2012 to May 2017. Adult surgical patients with DCM with moderate to severe myelopathy (mJOA scale score of 8-14) were randomized to receive either riluzole or placebo. The present study was conducted from July to December 2023. Intervention: Riluzole (50 mg twice daily) or placebo for a total of 6 weeks, including 2 weeks prior to surgery and 4 weeks following surgery. Main Outcomes and Measures: The primary outcome measure was a difference in clinical improvement from baseline to 1-year follow-up, assessed using a global statistical test (GST). The 36-Item Short Form Health Survey Physical Component Score (SF-36 PCS), arm and neck pain numeric rating scale (NRS) scores, American Spinal Injury Association (ASIA) motor score, and Nurick grade were combined into a single summary statistic known as the global treatment effect (GTE). Results: Overall, 290 patients (riluzole group, 141; placebo group, 149; mean [SD] age, 59 [10.1] years; 161 [56%] male) were included. Riluzole showed a significantly higher probability of global improvement compared with placebo at 1-year follow-up (GTE, 0.08; 95% CI, 0.00-0.16; P = .02). A similar favorable global response was seen at 35 days and 6 months (GTE for both, 0.07; 95% CI, -0.01 to 0.15; P = .04), although the results were not statistically significant. Riluzole-treated patients had at least a 54% likelihood of achieving better outcomes at 1 year compared with the placebo group. The ASIA motor score and neck and arm pain NRS combination at 1 year provided the best-fit parsimonious model for detecting a benefit of riluzole (GTE, 0.11; 95% CI, 0.02-0.16; P = .007). Conclusions and Relevance: In this secondary analysis of the CSM-PROTECT trial using a global outcome technique, riluzole was associated with improved clinical outcomes in patients with DCM. The GST offered probability-based results capable of representing diverse outcome scales and should be considered in future studies assessing spine surgery outcomes.

Effect of dietary supplementation with sanguinarine on meat quality and lipid metabolism of broilers.

Dietary Macleaya cordata extract (MCE) can improve the meat quality of poultry. However, the specific mechanism by which MCE regulates the meat quality has not been clarified yet. Sanguinarine (SAN) is one of the important natural active components in MCE. Our study aims to explore the regulatory mechanism of dietary SAN supplementation on meat quality through transcriptomic and gut microbiome analysis, thereby providing a basis for regularing meat quality with MCE. 240 1-day-old broilers were divided into 4 groups according to different doses of SAN (0, 0.225, 0.75, and 2.25 mg/kg). The results indicated that SAN significantly improve the physicochemical quality indicators of breast and thigh muscle in broilers, improved the serum biochemical indexes. Through transcriptome sequencing analysis of the liver and ileum tissues of broilers, we found that the differentially expressed genes induced by SAN were mainly enriched in lipid metabolism, which were related to the peroxisome proliferator-activated receptor (PPAR) pathway. It reconfirmed that SAN can regulate lipid metabolism in the body by promoting the expression of genes related to cholesterol metabolism, fatty acid transport and oxidation by RT-PCR, this ultimately affects the physicochemical quality of muscle. Additionally, through 16S rRNA sequencing analysis, we found that dietary addition of SAN increased the relative abundance of Bacteroides, Lactobacillus and unclassified_f_Lachnospiraceae, while decreased the relative abundance of Alistipes in ceca. To further investigate the impact of gut microbiota on lipid metabolism, we conducted a correlation analysis of PPAR pathway factor expression in cecum tissue and microflora structure. The results showed that Bacteroides exhibited a positive correlation with the expression of most genes in the PPAR signaling pathway. Unclassified_f__Lachnospiraceae is positively correlated with PPARγ, Cytochrome P450 family 7 subfamily A member 1 (CYP7A1) and Acyl-CoA synthetase long-chain family member 5 (ACSL5). In conclusion, dietary addition of SAN can promote the genes expression of the PPAR pathway, target the regulation of intestinal microflora structure and abundance and regulate lipid metabolism, thereby improving meat quality of broilers.

Maternal intervention with a combination of galacto-oligosaccharides and hyocholic acids during late gestation and lactation increased the reproductive performance, colostrum composition, antioxidant and altered intestinal microflora in sows.

Introduction: This study was conducted to evaluate the effects of dietary galacto-oligosaccharides (GOS) and hyocholic acids (HCA) during late gestation and lactation on reproductive performance, colostrum quality, antioxidant capacity and gut microbiota in multiparous sows. Methods: A total of 60 healthy multiparous cross-bred sows (Landrace × Yorkshire) were randomly fed 4 groups diets as follows: the basal diets (CTRL group), or the basal diets containing only 600 mg/kg GOS (GOS group), 600 mg/kg GOS + 100 mg/kg HCA (GOS + Low HCA group), and 600 mg/kg + 200 mg/kg HCA (GOS + High HCA group) from d 85 of gestation to weaning. Multiple parameters of sows were determined. Results: There was a trend of shortening the labor process of sows (p = 0.07) in the GOS group and GOS + Low/High HCA group. Compared with the CTRL group, the GOS + Low/High HCA group increased the average piglets weight at birth (p < 0.05), and increased the IgA concentration of colostrum (p < 0.05). In addition, serum triglyceride (TG) concentration was lower (p < 0.05), and serum total antioxidant capacity (T-AOC) was higher (p < 0.05) in the GOS and GOS + Low/High HCA groups than in the CTRL group at farrowing. Serum catalase (CAT) activities was higher in the GOS and GOS + High HCA groups than in the CTRL group at farrowing. The 16S rRNA analysis showed that GOS combination with high-dose HCA shaped the composition of gut microbiota in different reproductive stages (d 107 of gestation, G107; d 0 of lactation, L0; d 7 of lactation, L7). At the phylum level, the relative abundance of Bacteroidota and Desulfobacterota in G107, Bacteroidota, and Proteobacteria in L0, and Planctomycetota in L7 was increased in GOS + High HCA group (p < 0.05). Spearman correlation analysis showed that Streptococcus was positively correlated with the serum TG but negatively correlated with the average piglets weight at birth (p < 0.05). Conclusion: This investigation demonstrated that the administration of galacto-oligosaccharides (GOS) in conjunction with hyocholic acids (HCA), to sows with nutrient restrictions during late gestation and lactation, further improved their antioxidant capacity and milk quality. The observed beneficial effects of GOS + HCA supplementation could potentially be linked to an improvement in gut microbiota disorders of the sows.

Association Between MRI-Based Radiomics Features and Regional Lymph Node Metastasis in Intrahepatic Cholangiocarcinoma and Its Clinical Outcome.

BACKGROUND: Regional lymph node metastasis (LNM) assessment is crucial for predicting intrahepatic cholangiocarcinoma (iCCA) prognosis. However, imaging assessment has limitations for identifying LNM. PURPOSE: To investigate the association between MRI radiomics features, regional LNM status, and prognosis in iCCA. STUDY TYPE: Retrospective. SUBJECTS: Two hundred ninety-six patients (male = 197) with surgically confirmed iCCA. FIELD STRENGTH/SEQUENCE: 1.5 T and 3.0 T. DWI, T2WI, and contrast-enhanced T1WI. ASSESSMENT: Clinical information, radiologic, and MRI-based radiomics features associated with LNM status were collected to establish models. Performance of MRI, PET/CT, and the combined LNM models were compared in training (N = 207) and test (N = 89) datasets. Overall survival (OS) was compared based on LNM status. STATISTICAL TESTS: The independent features were selected by 5-fold cross-validation. The performance of MRI, PET/CT, and the models was evaluated using the area under receiver operating characteristic curve (AUC). Univariable and multivariable Cox regression were used to identify independent variables for OS. Kaplan-Meier curves were compared with the log-rank test between LNM positive and negative groups. P < 0.05 was considered statistically significant. RESULTS: Intrahepatic duct dilatation, enhancement pattern, and CA19-9 were independent clinicoradiologic features. The radiomics model was constructed by the independent radiomics features extracted from T2WI and delay phase T1WI. The combined LNM model showed AUC of 0.888, 0.884, and 0.811 in training, validation, and test cohorts with a positive net benefit. PET/CT exhibited similar sensitivity to the combined LNM model (0.750 vs. 0.733, P > 0.999) while the combined LNM model showed higher specificity (0.703 vs. 0.630, P = 0.039) in the test cohort. High risk of regional LNM was significantly associated with worse OS (median: 24 months) than low risk (median: 30 months, P < 0.0001). DATA CONCLUSIONS: The combined LNM model has the strongest correlation with LNM status for mass-forming iCCA patients. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

California Exodus? A Network Model of Population Redistribution in the United States.

Motivated by debates about California's net migration loss, we employ valued exponential-family random graph models to analyze the inter-county migration flow networks in the United States. We introduce a protocol that visualizes the complex effects of potential underlying mechanisms, and perform in silico knockout experiments to quantify their contribution to the California Exodus. We find that racial dynamics contribute to the California Exodus, urbanization ameliorates it, and political climate and housing costs have little impact. Moreover, the severity of the California Exodus depends on how one measures it, and California is not the state with the most substantial population loss. The paper demonstrates how generative statistical models can provide mechanistic insights beyond simple hypothesis-testing.

Acute Q fever pneumonia diagnosed by metagenomic next-generation sequencing.

INTRODUCTION: Q fever, a zoonotic disease caused by Coxiella burnetii (C. burnetii), presents diagnostic challenges due to its clinical and radiological nonspecificity, which often mimics community-acquired pneumonia, coupled with the limitations of traditional diagnostic methods. Metagenomic next-generation sequencing (mNGS) has become an indispensable tool in clinical diagnostics for its high-throughput pathogen identification capabilities. Herein, we detail a case of acute Q fever pneumonia diagnosed with mNGS. CASE PRESENTATION: The patient exhibited symptoms of fever, cough, expectoration, and diarrhea for three days, with the pathogen undetected in initial laboratory assessments. Bronchoscopy and bronchoalveolar lavage (BAL) were conducted, leading to the identification of C. burnetii in the lavage fluid via mNGS. Consequently, the patient was promptly initiated on a treatment regimen of 100 mg doxycycline, administered orally every 12 hours. RESULTS: Post-treatment, the patient's temperature normalized, and a full recovery was observed. The follow-up chest CT scan revealed complete resolution of the right lower lobe consolidation. CONCLUSIONS: The clinical presentation of Q fever pneumonia lacks specificity, making diagnosis based solely on symptoms and imaging challenging. mNGS offers a superior alternative for identifying elusive or rarely cultured pathogens.

Anterior capsulotomy combined with subthalamic nucleus deep brain stimulation for tardive dystonia.

BACKGROUND: Deep brain stimulation (DBS) has been reported as a therapy option for the motor dysfunction of severe tardive dystonia (TD). The major psychiatric diseases, however, are contraindications to DBS treatment in TD patients. METHODS: Six severe, medically refractory TD patients undergoing bilateral anterior capsulotomy combined with bilateral subthalamic nucleus (STN)-DBS treatment were studied retrospectively at two time points: pre-operation, and 1-3 years post-operation. Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) was used to assess the dystonia and disability. Depressive, anxiety, psychiatric symptoms, and Quality of Life (QoL) were evaluated using the 17-item Hamilton Depression Scale (HAMD-17), the 14-item Hamilton Anxiety Scale (HAMA-14), the Positive and Negative Syndrome Scale (PANSS), and 36-item Short-Form Health Survey (SF-36), respectively. RESULTS: After receiving the combination treatment for 25 ± 11.6 months (range, 12-41 months), significant clinical symptom improvements were reported in TD patients. BFMDRS motor and disability scores were ameliorated by 78.5 ± 32.0% (p = 0.031) and 76.5 ± 38.6% (p = 0.031), respectively. The HAMD-17 and HAMA-14 scores were reduced by 60.3 ± 27.9% (p = 0.007) and 60.0 ± 24.6% (p = 0.009), respectively. Furthermore, the PANSS scores of the comorbidity schizophrenia TD patients decreased by 58.1 ± 6.0% (p = 0.022), and the QoL improved by 59.7 ± 14.1% (SF-36, p = 0.0001). During the research, there were no notable adverse effects or problems. CONCLUSION: Bilateral anterior capsulotomy combined with bilateral STN-DBS may be an effective and relatively safe treatment option for severe TD comorbid with major psychiatric disorders.