A pharmacovigilance study of chronic kidney disease in diabetes mellitus patients with statin treatment by using the US Food and Drug Administration adverse event reporting system.

Background: Statins were regarded as a main medication for managing hypercholesterolemia. Administration of statin therapy could reduce the incidence of cardiovascular disease in individuals diagnosed with type 2 diabetes mellitus (DM), which was recognized by multipal clinical guidelines. But previous studies had conflicting results on whether the long-term use of statins could benefit the renal function in diabetic patients. Aim: To evaluate the association between statin treatment and Chronic Kidney Disease in DM patients. Methods: This is a retrospective disproportionality analysis and cohort study based on real-world data. All DM cases reported in US Food and Drug Administration adverse event reporting system (FAERS) between the first quarter of 2004 and the fourth quarter of 2022 were included. Disproportionality analyses were conducted by estimating the reporting odds ratio (ROR) and the information component (IC). We further compared the CKD odds ratio (OR) between the statins group and the other primary suspected drug group among the included diabetes mellitus cases. Results: We finally included 593647 DM cases from FAERS, 5113 (5.31%) CKD cases in the statins group and 8810 (1.77%) CKD cases in the control group. Data analysis showed that the statins group showed a significant CKD signal (ROR: 3.11, 95% CI: 3.00-3.22; IC: 1.18, 95% CI: 1.07-1.29). In case group with two or more statins treatment history, the CKD signal was even stronger (ROR: 19.56, 95% CI: 18.10-21.13; IC: 3.70, 95% CI:3.44-3.93) compared with cases with one statin treatment history. Conclusion: The impact of statin therapy on the progression of renal disease in individuals diagnosed with type 2 diabetes mellitus (DM) remains inconclusive. After data mining on the current FAERS dataset, we discovered significant signals between statin treatment and CKD in diabetic patients. Furthermore, the incidence rate of CKD was higher among DM patients who used statins compared to those who did not.

Extraction of Moso Bamboo Parameters Based on the Combination of ALS and TLS Point Cloud Data.

Extracting moso bamboo parameters from single-source point cloud data has limitations. In this article, a new approach for extracting moso bamboo parameters using airborne laser scanning (ALS) and terrestrial laser scanning (TLS) point cloud data is proposed. Using the field-surveyed coordinates of plot corner points and the Iterative Closest Point (ICP) algorithm, the ALS and TLS point clouds were aligned. Considering the difference in point distribution of ALS, TLS, and the merged point cloud, individual bamboo plants were segmented from the ALS point cloud using the point cloud segmentation (PCS) algorithm, and individual bamboo plants were segmented from the TLS and the merged point cloud using the comparative shortest-path (CSP) method. The cylinder fitting method was used to estimate the diameter at breast height (DBH) of the segmented bamboo plants. The accuracy was calculated by comparing the bamboo parameter values extracted by the above methods with reference data in three sample plots. The comparison results showed that by using the merged data, the detection rate of moso bamboo plants could reach up to 97.30%; the R2 of the estimated bamboo height was increased to above 0.96, and the root mean square error (RMSE) decreased from 1.14 m at most to a range of 0.35-0.48 m, while the R2 of the DBH fit was increased to a range of 0.97-0.99, and the RMSE decreased from 0.004 m at most to a range of 0.001-0.003 m. The accuracy of moso bamboo parameter extraction was significantly improved by using the merged point cloud data.

TMSOTf-Catalyzed C2-Sulfenylation of Indole Alkaloids Using N-Sulfenylsuccinimides: An Approach for the Total Synthesis of Isatindigotindolosides.

A TMSOTf-catalyzed C2-sulfenylation of indole alkaloids with N-sulfenylsuccinimides has been developed. This straightforward, metal-free, and cost-effective catalytic system produces valuable 2-thioindole derivatives with yields ranging from moderate to excellent. The synthetic applicability demonstrated includes the total syntheses of isatindigotindolosides I-IV.

Rhopaloic acid A triggers mitochondria damage-induced apoptosis in oral cancer by JNK/BNIP3/Nix-mediated mitophagy.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a frequently occurring type of head and neck cancer with a high mortality and morbidity rate. Rhopaloic acid A (RA), a terpenoid derived from sponges, has demonstrated a promising anti-tumor activity, but its effectiveness for treating OSCC remains unknown. PURPOSE: The aim of this study was to investigate whether RA inhibits the growth of OSCC. METHODS: Cell viability was evaluated using CCK-8 assays in OSCC cells (Ca9-22, HSC-3 and SAS) and in normal cells (HGF-1) treated with RA. DAPI staining, AO staining, JC-1 staining and immunofluorescence were used to determine apoptosis, mitochondrial membrane potential and autophagy in RA-treated OSCC cells. Protein expression levels were determined by western blotting. Furthermore, the anti-tumor effect of RA was confirmed in vivo using a zebrafish oral cancer xenotransplantation model. RESULTS: OSCC cells had a significantly reduced viability after RA treatment, but normal cells were not affected. Treatment with RA caused chromatin condensation in OSCC cells, which increased their expression of autophagy- and apoptosis-related proteins. Furthermore, RA caused mitochondrial damage and increased autophagosome formation. Mitophagy was also induced by RA through the JNK/BNIP3/Nix/LC3B pathway. The JNK inhibitor SP600125 prevented both RA-mediated cell death and mitophagy of OSCC cells. A zebrafish xenograft model demonstrated that RA inhibits OSCC growth. CONCLUSION: In conclusion, RA showed a potent anticancer activity in in vitro and in in vivo oral cancer models by promoting mitochondrial damage-induced apoptosis and mitophagy, which suggests that RA may be useful as a novel and effective treatment for OSCC.

Integrated Acetabular Prosthesis Versus Bone Grafting in Total Hip Arthroplasty for Crowe Type II and III Hip Dysplasia: A Retrospective Case-Control Study.

OBJECTIVE: Many methods of acetabular reconstruction with total hip arthroplasty (THA) for Crowe type II and III adult developmental dysplasia of the hip (DDH) acetabular bone defect have been implemented clinically. However, there was no study comparing the results of integrated acetabular prosthesis (IAP) with bone grafting (BG). This study aims to investigate the efficacy of IAP and BG for acetabular reconstruction in Crowe type II and III DDH. METHODS: The clinical data of 45 patients with unilateral Crowe type II and III DDH who underwent THA from January 2020 to January 2023 were retrospectively analyzed. The patients were divided into two groups: 25 patients using 3D-printed IAP (IAP group) and 20 patients using BG (BG group). The operation time and intraoperative blood loss were recorded. The clinical outcomes were assessed by Harris Hip Score (HHS) and full weight-bearing time. The radiological outcomes were evaluated by the radiological examination. Accordingly, intraoperative and postoperative complications were observed as well. The data between the two groups were compared by independent sample t-tests and the Mann-Whitney U rank sum test. RESULTS: There were no significant differences between the two groups in Harris Hip Score (HHS) (preoperative, 6 months postoperative, and the last follow-up), leg length discrepancy (LLD), cup inclination, cup anteversion, vertical center of rotation (V-COR), horizontal center of rotation (H-COR) (p > 0.05). The mean HHS in the IAP group was higher than in the BG group at 1 and 3 months postoperative (p < 0.001). The mean surgical time and blood loss in the IAP group were less than in the BG group (p < 0.001). The mean full weight-bearing time in the IAP group was shorter than in the BG group (p < 0.01). No complications were observed in either group during the follow-up period. CONCLUSION: IAP and BG have similar radiographic outcomes and long-term clinical efficacy in THA for Crowe type II and III DDH, but the IAP technique has higher surgical safety and facilitates the recovery of hip joint function, which is worthy of clinical promotion.

Application of Low-Salinity Waterflooding in Heavy Oil Sandstone Reservoir: Oil Recovery Efficiency and Mechanistic Study.

Low-salinity water injection (LSWI) is a recently emerged and promising technique to enhance oil recovery. In addition, it is attractive due to its relatively low-cost, environmental friendliness, and sustainability. However, the underlying mechanisms remain unclear, and very limited research has been conducted on heavy oil. To verify the feasibility of injecting a low-salinity aquifer water (LSAW) to improve the oil recovery of our target offshore heavy oil reservoir, first, a series of experiments on the core scale, including coreflooding and spontaneous imbibition experiments, were carried out. Furthermore, atomic force microscopy (AFM), contact angle, zeta potential measurement, as well as disjoining pressure calculations based on the Derjaguin-Landau-Verwey-Overbeek (DLVO) theory were carried out to explore the underlying governing mechanism at the microscopic scale. The secondary oil recovery factors of the coreflood tests are 67.11, 70.55, and 77.18% for seawater (SW), produced water (PW), and LSAW, respectively. The additional oil recoveries by LSAW when injected in tertiary modes are 6.38% after SW injection and 5.68% after PW injection. These results indicate that compared with SW and PW which have high brine salinity, the low-salinity brine from the subsurface aquifer (LSAW) can improve oil recovery in both secondary and tertiary modes. In addition, the oil recovery factors from the spontaneous imbibition tests (27.52% by LSAW, 17.32% by PW, and 14.00% by SW) and the insignificant variation of IFTs among the three brines lead to the anticipation that the LSAW can alter the rock to a more water-wet condition compared with SW and PW, thereby giving rise to a higher oil recovery factor in the coreflooding tests. By using AFM imaging and contact angle tests, we proved that the polar asphaltene could desorb from the rock surface and consequently reduce the water contact angle substantially when subjected to low-salinity brine. Furthermore, the zeta potential and the disjoining pressure results indicate that a more repulsive force was developed between oil and the rock under the low-salinity environment, which thereby promotes asphaltene desorption and consequent wettability alteration. Our work has paved the way to apply LSWI to the offshore heavy oil sandstone reservoir.

Randomized, double-blind, placebo-controlled trial of aripiprazole oral solution in children and adolescents with Tourette's disorder.

BACKGROUND: Aripiprazole is the most frequently recommended antipsychotic for the treatment of tics in children and adolescents with Tourette's disorder (TD). However, to date, a randomized controlled trial for aripiprazole oral solution has not been conducted despite being widely preferred by children. Therefore, we examined whether aripiprazole oral solution is effective for treating tics. METHODS: All patients received a flexible dose of aripiprazole oral solution (1 mg/mL, range: 2-20 mg) with a starting dose of 2 mg. The target dose for patients weighing < 50 kg was 2, 5, and 10 mg/day, and that for patients weighing ≥ 50 kg was 5, 10, 15, and 20 mg/day. The primary efficacy endpoint was the mean change in the Yale Global Tic Severity Scale-total tic score (YGTSS-TTS) from baseline to week 8. RESULTS: Of the 121 patients enrolled, 59 patients (96.7%) in the aripiprazole group and 53 patients (88.3%) in the placebo group completed the study. The aripiprazole group showed significantly greater improvement in the YGTSS-TTS from baseline to week 8 than the placebo group (least squares mean difference [95% confidence interval (CI)] -5.5 [95% CI - 8.4 to - 2.6]). At week 8, the response rate (i.e., percentage of patients with a Tourette's Syndrome Clinical Global Impression-Improvement score of 1 or 2) of the aripiprazole group (86.4%) was significantly higher than that of the placebo group (56.6%; odds ratio: 3.6, p < 0.001). The incidence of treatment-emergent adverse events (TEAEs) reported in at least one patient was 86.9% in the aripiprazole group and 65.5% in the placebo group. All TEAEs were mild or moderate in severity. No serious adverse events or deaths occurred during the study. CONCLUSIONS: Our findings suggest that aripiprazole oral solution is an effective, well-tolerated, and safe treatment for children and adolescents with TD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03487783. Registered 4 April 2018.

Hypoxia-enhanced YAP1-EIF4A3 interaction drives circ_0007386 circularization by competing with CRIM1 pre-mRNA linear splicing and promotes non-small cell lung cancer progression.

BACKGROUND: The progression of non-small cell lung cancer (NSCLC) is significantly influenced by circular RNAs (circRNAs), especially in tumor hypoxia microenvironment. However, the precise functions and underlying mechanisms of dysregulated circRNAs in NSCLC remain largely unexplored. METHODS: Differentially expressed circRNAs in NSCLC tissues were identified through high-throughput RNA sequencing. The characteristics of circ_0007386 were rigorously confirmed via Sanger sequencing, RNase R treatment and actinomycin D treatment. The effects of circ_0007386 on proliferation and apoptosis were investigated using CCK8, cloning formation assays, TUNEL staining, and flow cytometry assays in vitro. In vivo, xenograft tumor models were used to evaluate its impact on proliferation. Mechanistically, the regulatory relationships of circ_0007386, miR-383-5p and CIRBP were examined through dual luciferase reporter assays and rescue experiments. Additionally, we detected the binding of EIF4A3 to CRIM1 pre-mRNA by RNA immunoprecipitation and the interaction between YAP1 and EIF4A3 under hypoxic conditions by co-immunoprecipitation. RESULTS: Our investigation revealed a novel circRNA, designated as circ_0007386, that was upregulated in NSCLC tissues and cell lines. Circ_0007386 modulated proliferation and apoptosis in NSCLC both in vitro and in vivo. Functionally, circ_0007386 acted as a sponge for miR-383-5p, targeting CIRBP, which influenced NSCLC cell proliferation and apoptosis via the PI3K/AKT signaling pathway. Furthermore, under hypoxic conditions, the interaction between YAP1 and EIF4A3 was enhanced, leading to the displacement of EIF4A4 from binding to CRIM1 pre-mRNA. This facilitated the back-splicing of CRIM1 pre-mRNA, increasing the formation of circ_0007386. The circ_0007386/miR-383-5p/CIRBP axis was significantly associated with the clinical features and prognosis of NSCLC patients. CONCLUSIONS: Circ_0007386, regulated by YAP1-EIF4A3 interaction under hypoxia conditions, plays an oncogenic role in NSCLC progression via the miR-383-5p/CIRBP axis.

Pseudorabies virus infection increases the permeability of the mammalian respiratory barrier to facilitate Pasteurella multocida infection.

Interaction between viruses and bacteria during the development of infectious diseases is a complex question that requires continuous study. In this study, we explored the interactions between pseudorabies virus (PRV) and Pasteurella multocida (PM), which are recognized as the primary and secondary agents of porcine respiratory disease complex (PRDC), respectively. In vivo tests using mouse models demonstrated that intranasal inoculation with PRV at a sublethal dose induced disruption of murine respiratory barrier and promoted the invasion and damages caused by PM through respiratory infection. Inoculation with PRV also disrupted the barrier function of murine and porcine respiratory epithelial cells, and accelerated the adherence and invasion of PM to the cells. In mechanism, PRV infection resulted in decreased expression of tight junction proteins (ZO-1, occludin) and adherens junction proteins (ß-catenin, E-cadherin) between neighboring respiratory epithelial cells. Additionally, PRV inoculation at an early stage downregulated multiple biological processes contributing to epithelial adhesion and barrier functions while upregulating signals beneficial for respiratory barrier disruption (e.g., the HIF-1α signaling). Furthermore, PRV infection also stimulated the upregulation of cellular receptors (CAM5, ICAM2, ACAN, and DSCAM) that promote bacterial adherence. The data presented in this study provide insights into the understanding of virus-bacteria interactions in PRDC and may also contribute to understanding the mechanisms of secondary infections caused by different respiratory viruses (e.g., influenza virus and SARS-CoV-2) in both medical and veterinary medicine. IMPORTANCE: Co-infections caused by viral and bacterial agents are common in both medical and veterinary medicine, but the related mechanisms are not fully understood. This study investigated the interactions between the zoonotic pathogens PRV and PM during the development of respiratory infections in both cell and mouse models, and reported the possible mechanisms which included: (i) the primary infection of PRV may induce the disruption and/or damage of mammal respiratory barrier, thereby contributing to the invasion of PM; (ii) PRV infection at early stage accelerates the transcription and/or expression of several cellular receptors that are beneficial for bacterial adherence. This study may shed a light on understanding the mechanisms on the secondary infection of PM promoted by different respiratory viruses (e.g., influenza virus and SARS-CoV-2) in both medical and veterinary medicine.

Passion fruit HD-ZIP genes: Characterization, expression variance, and overexpression PeHB31 enhanced drought tolerance via lignin pathway.

The HD-ZIP (homeodomain-leucine zipper) genes hold significant importance in transcriptional regulation, especially in plant development and responses to abiotic stresses. However, a comprehensive study targeting HD-ZIP family members in passion fruit has been absent. In our current research, 34 HD-ZIP family members (PeHBs) were identified by bioinformatics analysis. Transcriptome analysis revealed that PeHBs exhibited distinct expression patterns when subjected to the four different abiotic stresses, and significant differential expression of PeHBs was also found among the three developmental stages of the fruit and between the purple and yellow genotype passion fruit leaves. An integrated metabolome and transcriptome analysis further revealed that the HD-ZIP III class gene PeHB31 (homologous to ATHB8), was co-upexpressed with lignans in yellow fruit P. edulis (commonly used as a resistance rootstock) when compared to purple fruit P. edulis. The transformation of Arabidopsis and yeast with the PeHB31 gene showed an enhancement in their capacity to withstand drought conditions. Notably, the transgenic Arabidopsis plants exhibited an increase in lignin content within the vascular tissues of their stems. This research lays the groundwork for future studies on the control mechanisms of lignin biosynthesis by HD-ZIP genes (especially HD-ZIP classes III and I) involved in drought tolerance.

Tale of two emergent games: Opinion dynamics in dynamical directed networks.

Unidirectional social interactions are ubiquitous in real social networks whereas undirected interactions are intensively studied. We establish a voter model in a dynamical directed network. We analytically obtain the degree distribution of the evolving network at any given time. Furthermore, we find that the average degree is captured by an emergent game. However, we find that the fate of opinions is captured by another emergent game. Beyond expectation, the two emergent games are typically different due to the unidirectionality of the evolving networks. The Nash equilibrium analysis of the two games facilitates us to give the criterion under which the minority opinion with few disciples initially takes over the population eventually for in-group bias. Our work fosters the understanding of opinion dynamics ranging from methodology to research content.

Adipose tissue insulin resistance index was inversely associated with gluteofemoral fat and skeletal muscle mass in Japanese women.

Associations of adipose tissue insulin resistance index (AT-IR, a product of fasting insulin and free fatty acids) with body fat mass and distribution and appendicular skeletal muscle mass (ASM) were compared with results of homeostasis-model assessment-insulin resistance (HOMA-IR) in 284 Japanese female university students and 148 their biological mothers whose BMI averaged < 23 kg/m2. Although mothers compared with daughters had higher BMI, body fat percentage, trunk fat to body fat (TF/BF) ratio and lower leg fat to body fat (LF/BF), AT-IR and HOMA-IR did not differ. We had multivariable linear regression analyses which included TF/BF ratio, LF/BF ratio, weight-adjusted ASM (%ASM), height-adjusted ASM index (ASMI), fat mass index (FMI), and body fat percentage. In young women, AT-IR was independently associated with LF/BF ratio (Standardized ß [Sß]: - 0.139, p = 0.019) and ASMI (Sß: - 0.167, p = 0.005). In middle-aged women, LF/BF ratio (Sß: - 0.177, p = 0.049) and %ASM (Sß: - 0.205, p = 0.02) emerged as independent determinants of AT-IR. HOMA-IR was associated with TF/BF ratio and FMI, a proxy of abdominal and general adiposity, respectively, in both young and middle-aged women. The inverse association of AT-IR with leg fat may support the notion that limited peripheral adipose storage capacity and small skeletal muscle size are important etiological components in insulin-resistant cardiometabolic disease in Japanese women.

Optimal tooth sectioning using a surgical handpiece and elevator: a finite element study of horizontally deeply impacted mandibular third molars.

OBJECTIVES: To conduct a finite element analysis of the impact of different variables on tooth sectioning efficiency and trauma to surrounding tissues when utilizing high-speed surgical handpieces and elevators. METHODS: CBCT data from the horizontally impacted third mandibular molar (M3M) of a patient were utilized to establish digital models of the M3M, adjacent M2M, and surrounding bone. To simulate tooth sectioning, a 3D finite element model was established with the following variables: remaining tooth tissue thickness (1-5 mm), tooth section fissure width (1-3 mm), elevator depth in fissure (2-6 mm), elevator position (buccal, lingual, central), elevator width (2-5 mm), and application of force (rotating, levering). Using this model, the distribution of stress on the M3M and the surrounding tissue was assessed while measuring tooth sectioning efficiency and trauma to the surrounding tissue. RESULTS: Factors associated with uniform stress at the site of sectioning included thin (≤ 3 mm) remaining tooth tissue, appropriate fissure width (~ 2 mm), a wide (≥ 4 mm) elevator, and central elevator positioning. Levering the elevator yielded greater stress on the M3M than rotating force. Greater sectioning efficiency was associated with increased stress placed on the distobuccal side of M2M. CONCLUSIONS: Tooth sectioning efficiency can be improved by adjusting the high-speed surgical handpiece and elevator. However, it is important to remain attentive to the trauma to which adjacent teeth are exposed during this process. CLINICAL SIGNIFICANCE: These results offer guidance for approaches to improving operator efficiency and reducing trauma to surrounding tissues during tooth sectioning.

Prognostic significance of dynamic changes in liver stiffness measurement in patients with chronic hepatitis B and compensated advanced chronic liver disease.

BACKGROUND AND AIM: Liver stiffness measurements (LSMs) are promising for monitoring disease progression or regression. We assessed the prognostic significance of dynamic changes in LSM over time on liver-related events (LREs) and death in patients with chronic hepatitis B (CHB) and compensated advanced chronic liver disease (cACLD). METHODS: This retrospective study included 1272 patients with CHB and cACLD who underwent at least two measurements, including LSM and fibrosis score based on four factors (FIB-4). ΔLSM was defined as [(follow-up LSM - baseline LSM)/baseline LSM × 100]. We recorded LREs and all-cause mortality during a median follow-up time of 46 months. Hazard ratios (HRs) and confidence intervals (CIs) for outcomes were calculated using Cox regression. RESULTS: Baseline FIB-4, baseline LSM, ΔFIB-4, ΔLSM, and ΔLSM/year were independently and simultaneously associated with LREs (adjusted HR, 1.04, 95% CI, 1.00-1.07; 1.02, 95% CI, 1.01-1.03; 1.06, 95% CI, 1.03-1.09; 1.96, 95% CI, 1.63-2.35, 1.02, 95% CI, 1.01-1.04, respectively). The baseline LSM combined with the ΔLSM achieved the highest Harrell's C (0.751), integrated AUC (0.776), and time-dependent AUC (0.737) for LREs. Using baseline LSM and ΔLSM, we proposed a risk stratification method to improve clinical applications. The risk proposed stratification based on LSM performed well in terms of prognosis: low risk (n = 390; reference), intermediate risk (n = 446; HR = 3.38), high risk (n = 272; HR = 5.64), and extremely high risk (n = 164; HR = 11.11). CONCLUSIONS: Baseline and repeated noninvasive tests measurement allow risk stratification of patients with CHB and cACLD. Combining baseline and dynamic changes in the LSM improves prognostic prediction.

DNA break induces rapid transcription repression mediated by proteasome-dependent RNAPII removal.

A DNA double-strand break (DSB) jeopardizes genome integrity and endangers cell viability. Actively transcribed genes are particularly detrimental if broken and need to be repressed. However, it remains elusive how fast the repression is initiated and how far it influences the neighboring genes on the chromosome. We adopt a recently developed, very fast CRISPR to generate a DSB at a specific genomic locus with precise timing, visualize transcription in live cells, and measure the RNA polymerase II (RNAPII) occupancy near the broken site. We observe that a single DSB represses the transcription of the damaged gene in minutes, which coincides with the recruitment of a damage repair protein. Transcription repression propagates bi-directionally along the chromosome from the DSB for hundreds of kilobases, and proteasome is evoked to remove RNAPII in this process. Our method builds a foundation to measure the rapid kinetic events around a single DSB and elucidate the molecular mechanism.

Rhodium(III)-Catalyzed Intramolecular Cyclization and Sequential Aromatization of Ynamides with Propargyl Esters: Access to 2,5-Dihydropyrroles and Pyrroles.

Disclosed herein is a rhodium(III)-catalyzed intramolecular cyclization of ynamides with propargyl esters. A variety of highly functionalized 2,5-dihydropyrroles were obtained in moderate to good yields with high E/Z selectivities. Subsequent oxidation of the products gave valuable pyrrole derivatives. Additionally, scale-up reactions and late-stage derivatizations highlight the potential synthetic utility of this methodology.

Associations of adipose insulin resistance index with leg (gluteofemoral) fat (inverse) and serum alanine aminotransferase (positive) in young Japanese women.

Aim: Associations of the adipose tissue insulin resistance index (AT-IR, a product of fasting insulin and free fatty acid) with body fat distribution and the ratio of alanine to aspartate aminotransferase (ALT/AST), a marker of hepatosteatosis, were examined in the context of the metabolic syndrome. Methods: Legs, the trunk and body fat by DXA, blood pressure (BP) and blood chemistry were measured in 284 young Japanese female university students and 148 middle-aged biological mothers whose BMI averaged <23 kg/m2. Results: Young women had higher leg fat/body fat and lower trunk fat/body fat ratio (both p < 0.001) compared with middle-aged women but AT-IR did not differ between the two groups. We had multivariable linear regression analysis for AT-IR as a dependent variable including leg fat/body fat ratio, trunk fat/body fat ratio, fasting glucose, triglyceride, HDL cholesterol and systolic BP as independent variables. Leg fat/body fat ratio, fasting glucose and triglyceride (p = 0.013, 0.009 and 0.016, respectively) emerged as determinants of AT-IR in young women. Trunk fat/body fat ratio and fasting glucose (p = 0.003 and 0.019, respectively) emerged in middle-aged women. In a model which included ALT/AST as an additional independent variable, ALT/AST (p = 0.016) was the fourth independent determinant in young women and the single determinant of AT-IR in middle-aged women (p < 0.001). Conclusion: In young Japanese women, adipose tissue insulin resistance was associated with reduced leg fat, a subtle partial lipodystrophy-like phenotype associated with reduced adipose tissue expandability. It was associated with elevated trunk (abdominal) fat in middle-aged women and with ALT/AST, a marker of hepatosteatosis, in two groups of Japanese women, suggesting ectopic fat deposition associated with reduced adipose tissue expandability.

Casual associations of thyroid function with inflammatory bowel disease and the mediating role of cytokines.

Background: Previous observational epidemiological studies have suggested a potential association between thyroid function and inflammatory bowel disease (IBD). However, the findings remain inconclusive, and whether this association is causal remains uncertain. The objective of this study is to investigate the causal association between thyroid function and IBD. Methods: Genome-wide association studies (GWAS) involving seven indicators of thyroid function, IBD, and 41 cytokines were analyzed. Bidirectional two-sample Mendelian randomization (MR) and multivariable MR were conducted to examine the causal relationship between thyroid function and IBD and to explore the potential mechanisms underlying the associations. Results: Genetically determined hypothyroidism significantly reduced the risk of CD (odds ratio [OR] = 0.761, 95% CI: 0.655-0.882, p < 0.001). Genetically determined reference-range TSH was found to have a suggestive causal effect on IBD (OR = 0.931, 95% CI: 0.888-0.976, p = 0.003), (Crohn disease) CD (OR = 0.915, 95% CI: 0.857-0.977, p = 0.008), and ulcerative colitis (UC) (OR =0.910, 95% CI: 0.830-0.997, p = 0.043). In reverse MR analysis, both IBD and CD appeared to have a suggestive causal effect on the fT3/fT4 ratio (OR = 1.002, p = 0.013 and OR = 1.001, p = 0.015, respectively). Among 41 cytokines, hypothyroidism had a significant impact on interferon-inducible protein-10 (IP-10) (OR = 1.465, 95% CI: 1.094-1.962, p = 0.010). The results of multivariable MR showed that IP-10 may mediate the causal effects of hypothyroidism with CD. Conclusion: Our results suggest that an elevated TSH level reduces the risk of CD, with IP-10 potentially mediating this association. This highlights the pituitary-thyroid axis could serve as a potential therapeutic strategy for CD.

Several Feature Extraction Methods Combined with Near-Infrared Spectroscopy for Identifying the Geographical Origins of Milk.

Milk is a kind of dairy product with high nutritive value. Tracing the origin of milk can uphold the interests of consumers as well as the stability of the dairy market. In this study, a fuzzy direct linear discriminant analysis (FDLDA) is proposed to extract the near-infrared spectral information of milk by combining fuzzy set theory with direct linear discriminant analysis (DLDA). First, spectral data of the milk samples were collected by a portable NIR spectrometer. Then, the data were preprocessed by Savitzky-Golay (SG) and standard normal variables (SNV) to reduce noise, and the dimensionality of the spectral data was decreased by principal component analysis (PCA). Furthermore, linear discriminant analysis (LDA), DLDA, and FDLDA were employed to transform the spectral data into feature space. Finally, the k-nearest neighbor (KNN) classifier, extreme learning machine (ELM) and naïve Bayes classifier were used for classification. The results of the study showed that the classification accuracy of FDLDA was higher than DLDA when the KNN classifier was used. The highest recognition accuracy of FDLDA, DLDA, and LDA could reach 97.33%, 94.67%, and 94.67%. The classification accuracy of FDLDA was also higher than DLDA when using ELM and naïve Bayes classifiers, but the highest recognition accuracy was 88.24% and 92.00%, respectively. Therefore, the KNN classifier outperformed the ELM and naïve Bayes classifiers. This study demonstrated that combining FDLDA, DLDA, and LDA with NIR spectroscopy as an effective method for determining the origin of milk.