The Multifaceted Roles of Hippo-YAP in Cardiovascular Diseases.

The Hippo-yes-associated protein (YAP) signaling pathway plays a crucial role in cell proliferation, differentiation, and death. It is known to have impact on the progression and development of cardiovascular diseases (CVDs) as well as in the regeneration of cardiomyocytes (CMs). However, further research is needed to understand the molecular mechanisms by which the Hippo-YAP pathway affects the pathological processes of CVDs in order to evaluate its potential clinical applications. In this review, we have summarized the recent findings on the role of the Hippo-YAP pathway in CVDs such as myocardial infarction, heart failure, and cardiomyopathy, as well as its in CM development. This review calls attention to the potential roles of the Hippo-YAP pathway as a relevant target for the future treatment of CVDs.

Puerarin: a hepatoprotective drug from bench to bedside.

Pueraria is a time-honored food and medicinal plant, which is widely used in China. Puerarin, the main component extracted from pueraria, has a variety of pharmacological characteristics. In recent years, puerarin has received increasing attention for its significant hepatoprotective effects, such as metabolic dysfunction-associated steatotic liver disease, alcohol-related liver disease, and hepatic carcinoma. This paper explores the pharmacological effects of puerarin on various liver diseases through multiple mechanisms, including inflammation factors, oxidative stress, lipid metabolism, apoptosis, and autophagy. Due to its restricted solubility, pharmacokinetic studies revealed that puerarin has a low bioavailability. However, combining puerarin with novel drug delivery systems can improve its bioavailability. Meanwhile, puerarin has very low toxicity and high safety, providing a solid foundation for its further. In addition, this paper discusses puerarin's clinical trials, highlighting its unique advantages. Given its excellent pharmacological effects, puerarin is expected to be a potential drug for the treatment of various liver diseases.

Effects of traditional Chinese medicine on outcomes and costs of dementia care: results from a retrospective real-world study.

OBJECTIVES: This study aims to assess the impact of Traditional Chinese Medicine (TCM) on dementia patients, utilizing real-world data. Specifically, it seeks to evaluate how TCM influences clinical outcomes by examining changes in the Clinical Dementia Rating (CDR) and Mini-Mental State Examination (MMSE) scores, as well as its effect on medical expenses over a two-year period. Data from a multi-center research database spanning from 2004 to 2021 will be used to achieve these objectives, addressing the current gap in empirical data concerning intuitive outcomes and cognitive function assessments. METHODS: Propensity score matching was adopted to improve comparability among the intervention and control groups. Due to repeated dependent variable measurements, the generalized estimating equation was used to control for socio-demographic characteristics, regional characteristics, and Western medicine treatments for dementia. RESULTS: After propensity score matching, a total of 441 research subjects were included: 90 in the TCM intervention group and 351 in the non-TCM intervention group. The results of multivariate regression analysis showed that compared with the non-TCM intervention group, the MMSE scores in the TCM intervention group increased by 0.608 points each year. The annual change in CDR scores in the TCM intervention group was 0.702 times that of the non-TCM utilization group. After TCM intervention, annual outpatient expenses increased by US$492.2, hospitalization expenses increased by US$324.3, and total medical expenses increased by US$815.9, compared with the non-intervention group. CONCLUSIONS: TCM interventions significantly decelerate cognitive decline in dementia patients, evidenced by slower reductions in MMSE scores and mitigated increases in CDR scores. However, these benefits are accompanied by increased medical expenses, particularly for outpatient care. Future healthcare strategies should balance the cognitive benefits of TCM with its economic impact, advocating for its inclusion in dementia care protocols.

The observation that older men suffer from hip fracture at DXA T-scores higher than older women and a proposal of a new low BMD category, osteofrailia, for predicting fracture risk in older men.

The clinical significance of osteoporosis lies in the occurrence of fragility fractures (FFx), and the most relevant fracture site is the hip. The T-score is defined as follows: (BMDpatient-BMDyoung adult mean)/SDyoung adult population, where BMD is bone mineral density and SD is the standard deviation. When the femoral neck (FN) is measured in adult Caucasian women, a cutpoint value of patient BMD of 2.5 SD below the young adult mean BMD results in a prevalence the same as the lifetime risk of hip FFx for Caucasian women. The FN T-score criterion for classifying osteoporosis in older Caucasian men has been provisionally recommended to be - 2.5, but debates remain. Based on a systematic literature review, we noted that older men suffer from hip FFx at a FN T-score approximately 0.5-0.6 higher than older women. While the mean hip FFx FN T-score of around - 2.9 for women lies below - 2.5, the mean hip FF FN T-score of around - 2.33 for men lies above - 2.5. This is likely associated with that older male populations have a higher mean T-score than older female populations. We propose a new category of low BMD status, osteofrailia, for older Caucasian men with T-score ≤ - 2 (T-score ≤ - 2.1 for older Chinese men) who are likely to suffer from hip FFx. The group with T-score ≤ - 2 for older Caucasian men is comparable in prevalence to the group with T-score ≤ - 2.5 for older Caucasian women. However, older men in such category on average have only half the FFx risk as that of older women with osteoporotic T-score.

Use of Sodium-glucose cotransporter 2 (SGLT 2) inhibitor is associated with reduced emergency room visits and hospitalizations in patients with Chronic obstructive pulmonary disease (COPD) and type 2 Diabetes Mellitus.

BACKGROUND: The Sodium-Glucose Cotransporter 2 inhibitors (SGLT2i) are a class of anti-diabetic medications that confer cardio-renal-metabolic (CRM) benefits. Emerging evidence also suggests that these agents provide better benefits for chronic pulmonary conditions, especially chronic obstructive pulmonary disease (COPD). RESEARCH QUESTION: We aimed to assess the association between SGLT2i use and outcomes in patients with COPD and concomitant Type 2 Diabetes Mellitus (T2DM). STUDY DESIGN AND METHODS: We conducted a retrospective cohort study on adults with T2DM and COPD in a primary care clinic from January 01, 2019 to 01/01//2023. Patients were categorized into two groups based on SGLT2i use. We collected demographic information and outcomes such as emergency room (ER) visits, hospitalizations secondary to COPD exacerbation over the period of four years and time to hospitalization and ER visits. Chi-square analysis was used for categorical variables, whereas an unpaired t-test was used for continuous variables. Cox regression was performed to identify significant prognostic factors of hospitalization and ER visits. A Kaplan-Meir analysis was used to visualize the probability of non-hospitalization and the probability of not visiting the ER. Statistical significance was set at p-value <0.05. RESULTS: Of the 220 patients screened, 94 met the inclusion criteria, of which 20 patients (21.3 %) had SGLT2i use at admission, and 74 (78.7 %) did not. Baseline demographic information were well-matched between the two groups. SGLT2i use was associated with a significant reduction in ER visits (70 % vs. 97.3 %, p-0.001) and the number of hospitalizations (55 % vs 87.8 %, p-0.001). Further multivariate analysis showed lower hazards of hospitalization (adjusted HR-0.156; CI:0.073 to 0.331) and ER visits (HR)-0.232; CI:0.118 to 0.453) in patients on SGLT2i. INTERPRETATION: In patients with T2DM with COPD, SGLT2i use was associated with reduced ER visits and hospitalizations related to COPD. This protective effect of SGLT2i could be explained by reduced systemic proinflammatory markers and increased anti-inflammatory markers via inhibition of Node like receptor protein 3(NLRP3) inflammasome activation in multiple tissues, including the lungs.

In vitro antioxidant and protective effects of the extract of Broussonetia papyrifera leaves on imiquimod-induced skin lesions in psoriasis-like mice.

Psoriasis is a chronic inflammatory immune-related skin disease. According to literature reports, the leaves of Broussonetia papyrifera exhibit antioxidant, immune-enhancing and antibacterial effects. These leaves are not only used clinically for the treatment of superficial fungal infections and hepatitis, but also used in the development of health food. However, the treatment of psoriasis with the leaves of B. papyrifera has not been reported yet. The in vitro antioxidant activity of B. papyrifera leaf extract was investigated by DPPH, OH and ABTS assays. Furthermore, IMQ was used to induce a mouse psoriasis-like model and HE staining, enzyme-linked immunosorbent assay and biochemical kits were used to measure relevant pathological indexes. The results showed that the B. papyrifera leaf extract has certain antioxidant capacity in vitro, which was positively correlated with its concentration. In addition, the extract can not only improve IMQ-induced skin damage on the back of mice, inhibit TNF-α and IL-6 factor secretion, but also regulate activity of SOD and the serum levels of MDA. Its mechanism of action related to inhibiting the secretion of inflammatory factors and the regulation of oxidative stress in vivo.

Millmerranones G, a meroterpene isolated from a mangrove-derived fungus Aspergillus sp. GXIMD 03004.

One new meroterpene derivative, millmerranones G (1), and three known analogues (2-4) were identified from the mangrove-derived fungus Aspergillus sp. GXIMD 03004, which was isolated from the leaves of mangrove Acanthus ilicifolius L. collected from Beibu Gulf in China. The structure of 1 was characterised by a comprehensive interpretation of the NMR spectroscopic and HRESIMS data. The absolute configuration for 1 was established using experimental and calculated ECD data. The anti-Vibrio activities of all compounds were evaluated, the result showed that compounds 1 and 2 has weak activity against Vibrio harveyi.

Fewer spine degenerations among Southeast Asians than among Southern Chinese suggests populations from a warmer climate have inherently better spine health.

Background: Compared with older Caucasians, older Chinese have remarkably lower prevalence and lower severity of spine degenerative changes. There have been few studies on Southeast East populations. This study aims to compare radiographic spine degeneration features among older Hong Kong (HK) Chinese, older Thais, and older Indonesians. Methods: This study included 195 Thai women (mean: 73.6 years), 202 Thai men (mean: 73.7 years), 227 Indonesian women (mean: 70.5 years), and 174 Indonesian men (mean: 70.2 years), as well as same number of gender- and age-matched HK Chinese. The recruitment plan was that the participants would represent the general older population of their respective communities. With spine radiograph, spine hyper-kyphosis, osteoarthritic wedging (OAw), acquired short vertebrae (SVa), general osteophyte formation, lumbar disc space narrowing, and lumbar spondylolisthesis were assessed. Results: Compared with Southeast Asians (Thais and Indonesian data together), Chinese women and men had a higher prevalence of hyper-kyphosis (24.9% vs. 16.4%), OAw (2.4% vs. 0.9%), general osteophyte formation (15.3% vs. 10.5%), lumber disc space narrowing (27.6% vs. 20.3%), and lumbar spondylolisthesis (20.7% vs. 15.3%). The trends were also consistent for sub-group data analyses. An even lower prevalence was noted among Indonesian women and men than among Thais in general osteophyte formation (5.9% vs. 14.1%), lumbar disc space narrowing (18.3% vs. 24.1%), and lumbar spondylolisthesis (11.4% vs. 19.3%). Conclusions: This study showed a lower prevalence of spine degeneration changes among older Thais and older Indonesians than among older Chinese. Indonesians, who inhabit an even warmer climate, show even fewer spine degeneration changes than Thais.

Super-silencer perturbation by EZH2 and REST inhibition leads to large loss of chromatin interactions and reduction in cancer growth.

Human silencers have been shown to regulate developmental gene expression. However, the functional importance of human silencers needs to be elucidated, such as whether they can form 'super-silencers' and whether they are linked to cancer progression. Here, we show two silencer components of the FGF18 gene can cooperate through compensatory chromatin interactions to form a super-silencer. Double knockout of two silencers exhibited synergistic upregulation of FGF18 expression and changes in cell identity. To perturb the super-silencers, we applied combinational treatment of an enhancer of zeste homolog 2 inhibitor GSK343, and a repressor element 1-silencing transcription factor inhibitor, X5050 ('GR'). Interestingly, GR led to severe loss of topologically associated domains and loops, which were associated with reduced CTCF and TOP2A mRNA levels. Moreover, GR synergistically upregulated super-silencer-controlled genes related to cell cycle, apoptosis and DNA damage, leading to anticancer effects in vivo. Overall, our data demonstrated a super-silencer example and showed that GR can disrupt super-silencers, potentially leading to cancer ablation.

[Curative effect analysis of anterior cervical discectomy and fusion in patients with cervical spondylosis of vertebral artery type].

OBJECTIVE: To investigate the clinical effect of anterior cervical discectomy and fusion (ACDF) in the treatment of cervical spondylosis of vertebral artery type(CSA). METHODS: The clinical data of 42 patients with CSA from January 2020 to January 2022 were retrospectively analyzed. There were 25 males and 17 females, aged from 30 to 74 years old with an average of (53.9±11.0) years old. There were 18 cases with single-segment lesions, 17 cases with two-segment lesions, and 7 cases with three-segment lesions. The American Academy of Otolaryngology-Head and Neck Surgery's Hearing and Balance Committee score (CHE), the Neck Disability Index (NDI) and the cervical curvature Cobb angle were recorded before surgery and after surgery at 6 months. RESULTS: All 42 ACDF patients were followed up for 6 to 30 months with an average of (14.0±5.2) months. The operative time ranged from 95 to 220 min with an average of (160.38±36.77) min, the intraoperative blood loss ranged from 30 to 85 ml with an average of (53.60±18.98) ml. Tow patients had mild postoperative dysphagia, which improved with symptomatic treatment such as nebulized inhalation. CHE score decreased from (4.05±0.96) preoperatively to (2.40±0.70) at 6 months postoperatively (t=12.97, P<0.05). The number of improved vertigo at 6 months postoperatively was 38, with an improvement rate of 90.5%. NDI score was reduced from (34.43±8.04) preoperatively to (20.76±3.91) at 6 months postoperatively (t=11.83, P<0.05). The cervical curvature Cobb angle improved from (8.04±6.70)° preoperatively to (12.42±5.23)° at 6 months postoperatively (t=-15.96, P<0.05). CONCLUSION: The ACDF procedure has outstanding clinical efficacy in treating CSA. The operation can rapidly relieve patients' episodic vertigo symptoms by relieving bony compression and reconstructing cervical curvature. However, it is necessary to strictly grasp the indications for surgery and clarify the causes of vertigo in patients, and ACDF surgery is recommended for CSA patients for whom conservative treatment is ineffective.

Care preparedness of family caregivers of maintenance hemodialysis patients: a cross-sectional study.

With the increasing number of maintenance hemodialysis (MHD) patients, growing attention has been paid to the quality of care. Strengthening care preparedness of family caregivers is essential to improving the nursing quality. The purpose of this study is to explore the care preparedness level of family caregivers of MHD patients and its influencing factors, so as to provide guidance for the development of targeted care interventions. A total of 237 family caregivers of MHD patients were recruited from the hemodialysis room of two tertiary hospitals in Wuhan using the Convenience sampling method. They were surveyed by the general data questionnaire, Care Preparedness Scale and Positive Aspects of Caregiving. Statistical analysis was conducted using IBM SPSS software, version 21.0. The statistical tests conducted in this study were two-tailed, and a significance level of P < 0.05 was deemed as statistically significant. The care preparedness and positive aspects of caregiving scores of family caregivers of MHD patients were 19.05 ± 5.64 and 31.28 ± 7.28 points, respectively. The care preparedness level of family caregivers was significantly positively correlated with positive aspects of caregiving (P < 0.01). The results of multiple linear regression analysis showed that the total nursing time and whether family caregivers had chronic diseases and positive aspects of caregiving were the main factors influencing their care preparedness (all P < 0.05). These three factors accounted for 49.6% of the variance. The care preparedness of family caregivers of MHD patients remains to be continuously improved. Medical staff should emphasize the important role of total nursing time, whether the caregiver has a chronic disease, and positive aspects of caregiving in improving care preparedness in this population. To achieve this end, medical staff can provide targeted support and guidance for caregivers according to the influencing factors, such as implementing group psychological education, strengthening the training, offering social support, remote intervention (including family caregivers' education through the media), and so on. Meanwhile, caregivers should be evaluated dynamically, and information and emotional support should be provided for them.

Super enhancer acquisition drives expression of oncogenic PPP1R15B that regulates protein homeostasis in multiple myeloma.

Multiple myeloma is a hematological malignancy arising from immunoglobulin-secreting plasma cells. It remains poorly understood how chromatin rewiring of regulatory elements contributes to tumorigenesis and therapy resistance in myeloma. Here we generate a high-resolution contact map of myeloma-associated super-enhancers by integrating H3K27ac ChIP-seq and HiChIP from myeloma cell lines, patient-derived myeloma cells and normal plasma cells. Our comprehensive transcriptomic and phenomic analyses prioritize candidate genes with biological and clinical implications in myeloma. We show that myeloma cells frequently acquire SE that transcriptionally activate an oncogene PPP1R15B, which encodes a regulatory subunit of the holophosphatase complex that dephosphorylates translation initiation factor eIF2α. Epigenetic silencing or knockdown of PPP1R15B activates pro-apoptotic eIF2α-ATF4-CHOP pathway, while inhibiting protein synthesis and immunoglobulin production. Pharmacological inhibition of PPP1R15B using Raphin1 potentiates the anti-myeloma effect of bortezomib. Our study reveals that myeloma cells are vulnerable to perturbation of PPP1R15B-dependent protein homeostasis, highlighting a promising therapeutic strategy.

Three-dimensional visualization technology for guiding one-step percutaneous transhepatic cholangioscopic lithotripsy for the treatment of complex hepatolithiasis.

BACKGROUND: Biliary stone disease is a highly prevalent condition and a leading cause of hospitalization worldwide. Hepatolithiasis with associated strictures has high residual and recurrence rates after traditional multisession percutaneous transhepatic cholangioscopic lithotripsy (PTCSL). AIM: To study one-step PTCSL using the percutaneous transhepatic one-step biliary fistulation (PTOBF) technique guided by three-dimensional (3D) visualization. METHODS: This was a retrospective, single-center study analyzing, 140 patients who, between October 2016 and October 2023, underwent one-step PTCSL for hepatolithiasis. The patients were divided into two groups: The 3D-PTOBF group and the PTOBF group. Stone clearance on choledochoscopy, complications, and long-term clearance and recurrence rates were assessed. RESULTS: Age, total bilirubin, direct bilirubin, Child-Pugh class, and stone location were similar between the 2 groups, but there was a significant difference in bile duct strictures, with biliary strictures more common in the 3D-PTOBF group (P = 0.001). The median follow-up time was 55.0 (55.0, 512.0) days. The immediate stone clearance ratio (88.6% vs 27.1%, P = 0.000) and stricture resolution ratio (97.1% vs 78.6%, P = 0.001) in the 3D-PTOBF group were significantly greater than those in the PTOBF group. Postoperative complication (8.6% vs 41.4%, P = 0.000) and stone recurrence rates (7.1% vs 38.6%, P = 0.000) were significantly lower in the 3D-PTOBF group. CONCLUSION: Three-dimensional visualization helps make one-step PTCSL a safe, effective, and promising treatment for patients with complicated primary hepatolithiasis. The perioperative and long-term outcomes are satisfactory for patients with complicated primary hepatolithiasis. This minimally invasive method has the potential to be used as a substitute for hepatobiliary surgery.

Impact and effect of imaging referral guidelines on patients and radiology services: a systematic review.

OBJECTIVES: The objective of this systematic review was to offer a comprehensive overview and explore the associated outcomes from imaging referral guidelines on various key stakeholders, such as patients and radiologists. MATERIALS AND METHODS: An electronic database search was conducted in Medline, Embase and Web of Science to retrieve citations published between 2013 and 2023. The search was constructed using medical subject headings and keywords. Only full-text articles and reviews written in English were included. The quality of the included papers was assessed using the mixed methods appraisal tool. A narrative synthesis was undertaken for the selected articles. RESULTS: The search yielded 4384 records. Following the abstract, full-text screening, and removal of duplication, 31 studies of varying levels of quality were included in the final analysis. Imaging referral guidelines from the American College of Radiology were most commonly used. Clinical decision support systems were the most evaluated mode of intervention, either integrated or standalone. Interventions showed reduced patient radiation doses and waiting times for imaging. There was a general reduction in radiology workload and utilisation of diagnostic imaging. Low-value imaging utilisation decreased with an increase in the appropriateness of imaging referrals and ratings and cost savings. Clinical effectiveness was maintained during the intervention period without notable adverse consequences. CONCLUSION: Using evidence-based imaging referral guidelines improves the quality of healthcare and outcomes while reducing healthcare costs. Imaging referral guidelines are one essential component of improving the value of radiology in the healthcare system. CLINICAL RELEVANCE STATEMENT: There is a need for broader dissemination of imaging referral guidelines to healthcare providers globally in tandem with the harmonisation of the application of these guidelines to improve the overall value of radiology within the healthcare system. KEY POINTS: The application of imaging referral guidelines has an impact and effect on patients, radiologists, and health policymakers. The adoption of imaging referral guidelines in clinical practice can impact healthcare costs and improve healthcare quality and outcomes. Implementing imaging referral guidelines contributes to the attainment of value-based radiology.

Anxiety and sleep quality in patients receiving maintenance hemodialysis: multiple mediating roles of hope and family function.

The objective of this cross-sectional study was to examine the extent of sleep quality among individuals undergoing maintenance hemodialysis (MHD) and to scrutinize whether hope and family function serve as mediators in the association between anxiety and sleep quality in this cohort. A convenience sampling method was used to recruit 227 patients receiving maintenance hemodialysis from two tertiary hospitals in Wuhan. Participants completed several self-report questionnaires, including the Sociodemographic questionnaire, Hospital Anxiety and Depression Scale, Athens Insomnia Scale, Herth Hope Index, and Family APGAR Index. As per the findings of the chain mediation analysis, it was observed that the sleep quality scores were directly predicted by anxiety. Moreover, anxiety positively predicted sleep quality scores through hope and family function as mediators. The observed types of mediation were partial mediation. The total indirect effect value was 0.354, indicating the mediating effect of hope and family function, while the total effect value was 0.481, representing the overall effect of anxiety on sleep quality. The total effect size was 73.60% (0.354/0.481), indicating that the mediation accounted for a significant portion of the relationship. This study established the chain mediating effect of hope and family function between anxiety and sleep quality in patients receiving maintenance hemodialysis. The findings highlight the importance of addressing anxiety and promoting hope and family function to improve sleep quality in this population. The findings suggest that healthcare professionals should be attentive to the anxiety levels of these patients and implement targeted interventions to help alleviate anxiety, enhance hope, and improve family functioning, with the ultimate goal of improving sleep quality in this population.

Research progresses of imaging studies on preoperative prediction of microvascular invasion of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the predominant form of primary liver cancer, accounting for approximately 90% of liver cancer cases. It currently ranks as the fifth most prevalent cancer worldwide and represents the third leading cause of cancer-related mortality. As a malignant disease with surgical resection and ablative therapy being the sole curative options available, it is disheartening that most HCC patients who undergo liver resection experience relapse within five years. Microvascular invasion (MVI), defined as the presence of micrometastatic HCC emboli within liver vessels, serves as an important histopathological feature and indicative factor for both disease-free survival and overall survival in HCC patients. Therefore, achieving accurate preoperative noninvasive prediction of MVI holds vital significance in selecting appropriate clinical treatments and improving patient prognosis. Currently, there are no universally recognized criteria for preoperative diagnosis of MVI in clinical practice. Consequently, extensive research efforts have been directed towards preoperative imaging prediction of MVI to address this problem and the relative research progresses were reviewed in this article to summarize its current limitations and future research prospects.

Mauritone A, a new polyketide from a fungal-bacterial symbiont Aspergillus spelaeus GXIMD 04541/Sphingomonas echinoides GXIMD 04532.

A new polyketide, mauritone A (1) with six known polyketides curvulone B (2), curvularin (3), 12-oxocurvularin (4), (10E,15S)-10,11-dehydrocurvularin (5), (11R,15S)-11-hydroxycurvularin (6), and (11S,15S)-11-hydroxycurvularin (7) were isolated from the fungal-bacterial symbiont Aspergillus spelaeus GXIMD 04541/Sphingomonas echinoides GXIMD 04532 derived from Mauritia arabica. Their structures were elucidated by extensive spectral analysis. All compounds (1-7) were evaluated for their anti-inflammatory effects. The inhibitory effects of 4, 5, and 7 on nitric oxide (NO) production were found to be significant, with IC50 values of 5.5 ± 0.26, 2.0 ± 0.31, and 8.3 ± 0.62 µM, respectively, surpassing that of the positive control quercetin (10.6 ± 0.64 µM). Compounds 3 and 6 exhibited moderate inhibition of NO, with IC50 values of 18.6 ± 0.53 and 12.7 ± 0.45 µM, respectively.

AANAT1 regulates insect midgut detoxification through the ROS/CncC pathway.

Insecticide resistance has been a problem in both the agricultural pests and vectors. Revealing the detoxification mechanisms may help to better manage insect pests. Here, we showed that arylalkylamine N-acetyltransferase 1 (AANAT1) regulates intestinal detoxification process through modulation of reactive oxygen species (ROS)-activated transcription factors cap"n"collar isoform-C (CncC): muscle aponeurosis fibromatosis (Maf) pathway in both the oriental fruit fly, Bactrocera dorsalis, and the arbovirus vector, Aedes aegypti. Knockout/knockdown of AANAT1 led to accumulation of biogenic amines, which induced a decreased in the gut ROS level. The reduced midgut ROS levels resulted in decreased expression of CncC and Maf, leading to lower expression level of detoxification genes. AANAT1 knockout/knockdown insects were more susceptible to insecticide treatments. Our study reveals that normal functionality of AANAT1 is important for the regulation of gut detoxification pathways, providing insights into the mechanism underlying the gut defense against xenobiotics in metazoans.

Adherence to a planetary health diet, genetic susceptibility, and incident cardiovascular disease: a prospective cohort study from the UK Biobank.

BACKGROUND: The influence of adherence to a planetary health diet (PHD) proposed by the EAT-Lancet Commission on cardiovascular disease (CVD) is inconclusive. Besides, whether genetic susceptibility to CVD can modify the association of PHD with CVD remains unknown. OBJECTIVE: We aimed to investigate the association between adherence to PHD and CVD, and to evaluate the interaction between PHD and genetic predisposition to CVD. METHODS: This study included 114,165 participants who completed at least two 24-h dietary recalls and were initially free of CVD from the UK Biobank. PHD score was calculated to assess adherence to PHD. Genetic risk was evaluated using the polygenic risk score. Incidence of total CVD, ischemic heart disease (IHD), atrial fibrillation (AF), heart failure (HF), and stroke were identified via electronic health records. Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: During a median follow-up of 9.9 y, 10,071 (8.8%) incident CVD cases were documented. Compared with participants with the lowest adherence to PHD, HRs (95% CIs) for total CVD, IHD, AF, HF, and stroke among those with the highest adherence were 0.79 (0.74, 0.84), 0.73 (0.67, 0.79), 0.90 (0.82, 0.99), 0.69 (0.59, 0.82), and 0.88 (0.75, 1.04), respectively. No significant interaction between the genetic risk of CVD and PHD was observed. Participants with high genetic risk and low PHD score, as compared with those with low genetic risk and high PHD score, had a 48% (95% CI: 40%, 56%) higher risk of CVD. The population-attributable risk (95% CI) of CVD for poor adherence to PHD ranged from 8.79% (5.36%, 12.51%) to 14.00% (9.00%, 18.88%). CONCLUSIONS: These findings suggest that higher adherence to PHD was associated with lower risk of total CVD, IHD, AF, and HF in populations across all genetic risk categories.

Age and gender differences of normative values of spleen diffusion MRI parameters.

This study investigates age and gender differences of normative values of spleen diffusion MRI parameters.We recruited 124 volunteers with MRI conducted at 1.5T. Diffusion imaging had b-values of 0, 2, 4, 7, 10, 15, 20, 30, 46, 60, 72, 100, 150, 200, 400, 600 s/mm2. ADC, IVIM-Dslow, IVIM-PF, IVIM-Dfast, and DDVD (diffusion-derived vessel density) were computed. DDVD is the signal difference between the b=0 s/mm2 image and b=2, 4 s/mm2 image. Only images without apparent artifacts and with good curving fitting were included in the analysis. Finally, 34 females (age: 20-71 years) and 69 males (22-70 years) were measured with ADC; 20 females (20-71 years) and 48 males (22-67 years) were measured with IVIM; 32 females (20-71 years) and 65 males (22-70 years) were measured with DDVD parameter.An age-related decrease in ADC was noted for females, while such a trend was not noted for males. A very high level of heterogeneity was noted for the data for the males, with the highest ADC value being 1.710 × 10-3mm 2/s and the lowest ADC value being 0.705 × 10-3 mm2/s when b=0 and 600 s/mm 2 were used for ADC calculation. A male-female data comparison did not show a statistically significant difference between the ADC median value. However, ADCs > 1.3 × 10-3 mm2/s were only seen among males. A very high level of heterogeneity was also noted for males' Dslow, with the highest value being 1.468 × 10-3 mm2/s and the lowest value being 0.600 × 10-3 mm2/s. Both PF and Dfast demonstrated a trend of age-related increase for older subjects. PF values were higher among males than females. However, no difference was noted for Dfast between males and females. DDVD did not show an age-related trend both for females and males. No difference was noted in DDVD values between males and females.Interpreting normal spleen diffusion MRI parameters should consider age and gender factors. · An age-related decrease in spleen ADC and IVIM-Dslow was seen for healthy females.. · There is a high level of heterogeneity for spleen ADC and IVIM-Dslow data for healthy males.. · IVIM modelled perfusion fraction and Dfast demonstrate an artificial trend of age-related increase for older subjects.. · Vessel density measured on diffusion imaging does not show an age-related trend.. · Yu W, Ma FZ, Huang H et al. Age and gender differences of normative values of spleen diffusion MRI parameters. Fortschr Röntgenstr 2024; DOI 10.1055/a-2357-9741.