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Abstract INTRODUCTION Changes to the brain due to Alzheimer's disease and other age‐related neuropathologies may present with cognitive and behavioral symptoms, even during preclinical and prodromal stages. While cognitive reserve is known to mitigate cognitive decline in the preclinical stages of Alzheimer's disease, links between cognitive reserve and behavioral symptoms remain unclear. This study investigates the relationship between cognitive reserve and mild behavioral impairment (MBI), a neurodegenerative behavioral prodrome. METHODS We analyzed cross‐sectional data from 1204 participants in the Canadian Platform for Research Online to Investigate Health, Quality of Life, Cognition, Behavior, Function, and Caregiving in Aging (CAN‐PROTECT) study. A cognitive reserve score (CRS) was generated based on education, occupation, and personal cognitive reserve proxies. MBI presence (MBI+) and MBI global and domain symptom severity were evaluated using the self‐reported MBI Checklist. Initial analyses examined the convergent validity of the CRS through associations with objective neuropsychological test performance and self‐reported cognitive symptoms (Everyday Cognition [ECog‐II] scale). Models were also fitted to assess MBI status and severity as functions of the CRS. RESULTS Higher CRS was associated with better neuropsychological test scores, lower odds of subjective cognitive decline (OR = 0.86, 95% CI: [0.76, 0.98], p = .03), and lower ECog‐II total score. Likewise, higher CRS was associated with lower odds of MBI+ (OR = 0.81, 95% CI: [0.71, 0.93], p = .003), and lower MBI symptom severity globally, and in impulse dyscontrol and social inappropriateness domains. DISCUSSION We provide preliminary evidence that engagement in activities known to preserve cognitive function in aging and disease may also preserve behavioral function. Future research should disentangle possible pathways through which cognitive reserve may preserve both cognition and behavior, explore common etiologies for these symptoms, and observe outcomes longitudinally to better understand these relationships. Highlights Education, occupation, and personal activities are cognitive reserve proxies. Cognitive reserve is linked to lower subjective cognitive decline in older persons. Cognitive reserve is linked to lower mild behavioral impairment odds and severity.

Abstract Source‐to‐sink systems respond to and therefore potentially record topographic and tectonic changes. North of the Tian Shan Belt, the Sikeshu subbasin of the SW Junggar Basin transitioned from active extension in the Triassic to post‐extensional subsidence in the Jurassic‐Cretaceous. Sediment in the Sikeshu subbasin has been shown to be derived from the Tianshan. However, the details of the source‐to‐sink system remain unclear and discrepancies exist between proxy records. The heavy minerals in the Middle Triassic in the Sikeshu subbasin are dominated by garnets. To investigate the garnet sources and decipher the Mesozoic source‐to‐sink evolution, we conducted petrological and sedimentary analysis and detrital garnet and tourmaline geochemistry. We found that the geochemistry of garnets in the Middle Triassic sandstone is most consistent with that of the skarns in the Yili Block (YB) in Tianshan, while the geochemistry of 55%–84% of garnets in other Mesozoic sandstones is consistent with that of garnets in amphibolites in the YB. The geochemistry of the tourmalines since the Upper Triassic is consistent with that of the meta‐sedimentary rocks in the YB and Central Tianshan Block. The dominance of garnets sourced from skarns in the Middle Triassic probably indicates a near‐source point provenance and the broader range of garnet compositions from the Upper Triassic–Lower Cretaceous suggests multiple sources. We infer that the point source changed to multiple sources, which is consistent with the zircon spectra changing from unimodal to multimodal. This change reflects the expansion of the drainage that accompanies a change from active rifting to a post‐rift stage.

Abstract INTRODUCTION Hearing loss (HL) and mild behavioral impairment (MBI) are non‐cognitive markers of dementia. This study investigated the relationship between hearing and MBI and explored the influence of hearing aid use on the treatment of hearing loss, both cross‐sectionally and longitudinally. METHODS Data were analyzed from National Alzheimer's Coordinating Center participants, age ≥50, dementia‐free at baseline, collected between 2005 and 2022. Three self‐report questions were used to generate a three‐level categorical hearing variable: No‐HL, Untreated‐HL, and Treated‐HL. MBI status was derived from the informant‐rated Neuropsychiatric Inventory Questionnaire (NPI‐Q) using a published algorithm. At baseline (n = 7080), logistic regression was used to examine the association between hearing status (predictor) and the presence of global and domain‐specific MBI (outcome), adjusting for age, sex, cognitive diagnosis, and apolipoprotein E4 (APOE4). Cox proportional hazard models with time‐dependent covariates were used to examine the effect of (1) hearing status as exposure on the rate of incident MBI (n = 5889); and (2) MBI as exposure on the rate of incident HL in those with no HL at baseline (n = 6252). RESULTS Cross‐sectionally, participants with Untreated‐HL were more likely to exhibit global MBI (adjusted odds ratio (aOR) = 1.66, 95% CI: 1.24–2.21) and individual MBI domains of social inappropriateness (aOR = 1.95, 95% CI: 1.06–3.39), affective dysregulation (aOR = 1.71, 95% CI: 1.21–2.38), and impulse dyscontrol (aOR = 1.71, 95% CI: 1.21–2.38), compared to those with No‐HL. Participants with Treated‐HL (i.e., hearing aid use) did not differ from No‐HL for odds of global or most MBI domains, except for impulse dyscontrol (aOR = 1.38, 95% CI: 1.05–1.81). Longitudinally, we found relationships between Treated‐HL and incident MBI (adjusted hazard ratio (aHR) = 1.29, 95% CI: 1.01–1.63) and between MBI and incident Untreated‐HL (aHR = 1.51, 95% CI: 1.19–1.94). DISCUSSION Our cross‐sectional results support that hearing aid use is associated with lower odds of concurrent global MBI in dementia‐free participants. Longitudinally, relationships were found between MBI and HL. The severity of HL was not assessed, however, and may require further exploration. Highlights Hearing Loss (HL) and mild behavioral impairment (MBI) are markers of dementia Cross‐sectionally: Untreated‐HL was associated with global MBI burden, but HL treated with hearing aids was not We found associations between MBI and incident Untreated‐HL

Abstract INTRODUCTION We compared three operational case definitions of mild behavioral impairment (MBI) in the context of MBI prevalence estimates and dementia risk modeling. METHODS Participants were dementia‐free older adults (n = 13701) from the National Alzheimer's Coordinating Center. Operational case definitions of MBI were generated based on neuropsychiatric symptoms at one (OV), two‐consecutive (TCV), or more than two‐thirds (TTV) of dementia‐free study visits. Definitions were compared in prevalence and in Cox regressions using MBI to predict incident dementia. RESULTS OV MBI was the most prevalent (54.4%), followed by TCV (32.3%) and TTV (26.7%) MBI. However, OV MBI had the lowest rate of incident dementia (hazard ratio [HR] = 2.54, 95% confidence interval [CI]: 2.33–2.78) and generated poorer model metrics than TCV MBI (HR = 4.06, 95% CI: 3.74–4.40) and TTV MBI (HR = 5.77, 95% CI: 5.32–6.26). DISCUSSION Case ascertainment with longer timeframe MBI operational case definitions may more accurately define groups at risk of dementia in datasets lacking tools designed to detect MBI. Highlights Mild behavioral impairment (MBI) can identify older adults at risk of dementia. Neuropsychiatric symptom (NPS) assessment tools can be proxy measures for MBI. Hazard for dementia was highest for MBI defined by NPS presence at more than two‐thirds of visits.

Background: Postextubation dysphagia is common in the ICU, with varying incidence rates. However, few studies have focused on ICU nurses' knowledge, attitudes and practices regarding postextubation dysphagia, as well as the various influencing factors., Aims: To investigate ICU nurses' knowledge, attitudes and practices regarding postextubation dysphagia and provide suggestions for improvement., Study Design: This was a multicentre cross-sectional survey. Data were collected using a validated questionnaire to assess knowledge, attitudes and practices regarding postextubation dysphagia., Results: A total of 510 valid questionnaires were analysed. The median scores with interquartile ranges for knowledge, attitudes and practices regarding postextubation dysphagia were 8 (7, 9), 8 (7, 9) and 4.9 (3.8, 6.2), respectively. Multivariate analysis revealed that knowledge scores were significantly influenced by education level, ICU experience and managerial role (p < .05). Nurses with a bachelor's degree (OR = 3.636; 95% CI: 1.587-8.33) or a master's degree and above (OR = 7.742; 95% CI: 1.968-30.465) demonstrated higher knowledge scores than those with a postsecondary diploma. Nurses in managerial roles had higher scores (OR = 1.924; 95% CI: 1.053-3.515). Attitude (OR = 1.616; 95% CI: 1.092-2.39) and practice scores (OR = 4.079; 95% CI: 2.692-6.182) were significantly impacted by targeted PED training (p < .05). The correlation analysis revealed a weak but significant correlation only between knowledge and attitudes (τb = 0.196, p < .001)., Conclusion: Education level, ICU experience, managerial role and targeted PED training may enhance knowledge, attitudes or practices individually but do not lead to cohesive improvement across all three areas. Relying on knowledge alone is far from sufficient to drive behavioural change, indicating the need for comprehensive interventions to bridge these gaps., Relevance to Clinical Practice: To bridge this gap, comprehensive interventions beyond standard training are essential. These may include applying an implementation science strategy to ensure that ICU nurses' enhanced knowledge and positive attitudes are consistently translated into clinical practice., (© 2025 The Author(s). Nursing in Critical Care published by John Wiley & Sons Ltd on behalf of British Association of Critical Care Nurses.)

Background: Cardiac hypertrophy is a precursor to heart failure and represents a significant global cause of mortality, thereby necessitating timely and effective therapeutic interventions. Zinc finger protein 36 (Zfp36) is recognised as a critical regulator of ferroptosis; however, its role and underlying mechanisms in cardiac hypertrophy remain largely unexplored. This study aims to investigate the regulatory function of Zfp36 in ferroptosis within the context of cardiac hypertrophy., Methods and Results: Single-cell sequencing analysis demonstrated a reduction in Zfp36 expression associated with cardiac hypertrophy. Zfp36 was observed to mitigate ferroptosis and reduce hypertrophic phenotypes in cardiomyocytes subjected to Angiotensin II (Ang II) and in myocardial tissues induced by transverse aortic constriction. The ferroptosis inhibitor Ferrostatin-1 was shown to alleviate hypertrophy when co-incubated with si-Zfp36 and Ang II. Mechanistically, Zfp36 binds to the 3' untranslated region (3'UTR) of Ythdc2 mRNA, facilitating its degradation. Ythdc2 subsequently binds to SLC7A11 mRNA, enhancing its decay, which leads to a reduction in glutathione (GSH) levels, thereby exacerbating ferroptosis and cardiac hypertrophy. Furthermore, overexpression of Ythdc2 reversed the protective effects conferred by Zfp36, while silencing of Ythdc2 counteracted the effects of Zfp36 knockdown., Conclusions: This study elucidates the role of Zfp36 in cardiac hypertrophy, specifically detailing its modulatory mechanism via the Ythdc2/SLC7A11/GSH ferroptosis pathway. These insights lay the groundwork for innovative approaches to understanding the pathological mechanisms underlying cardiac hypertrophy and enhancing clinical interventions., Key Points: Zfp36 was initially demonstrated to attenuate cardiac hypertrophy through the inhibition of ferroptosis in cardiomyocytes, providing a new target for therapeutic strategies targeting ferroptosis. Zfp36 facilitated the degradation of Ythdc2 mRNA by binding to it, subsequently inhibiting Ythdc2-mediated degradation of SLC7A11 mRNA, and maintaining GSH levels. This elucidates a previously unrecognized regulatory pathway in the context of cardiac hypertrophy., (© 2025 The Author(s). Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Background: Glycocalyx degradation is implicated in endothelial damage and microcirculatory dysfunction in sepsis, whereas the effectiveness of plasma syndecan-1 levels and sublingual microcirculatory parameters in evaluating sepsis's prognosis has not yet been determined. This study aims to track their dynamic changes and investigate the prognostic utility of these indexes in sepsis., Methods: In this prospective study conducted at the First Affiliated Hospital of Sun Yat-sen University, blood samples were collected from adult surgical septic patients within 2 days after intensive care unit admission measuring plasma syndecan-1 concentrations. Relevant sublingual microcirculatory parameters were also obtained simultaneously. Additionally, capillary refill time and serum lactate levels were recorded. The primary outcome was 30-day mortality., Results: Of the 74 patients enrolled, the 30-day mortality rate was 35.1%. Significantly, higher syndecan-1 levels were observed in nonsurvivors at baseline, day 1, and day 2 (62.43 [37.37 and 103.16] vs. 97.24 [52.95 and 186.40] ng/mL and p = 0.035; 62.22 [41.50 and 87.52] vs. 96.71 [60.82 and 176.00] ng/mL and p = 0.009; and 56.03 [39.16 and 94.48] vs. 87.69 [72.52 and 159.70] ng/mL and p = 0.005, respectively). High syndecan-1 levels (≥121 ng/mL) were associated with lower survival rates (p = 0.001) and an increase exceeding 8 ng/mL within 2 days indicated a higher mortality risk (p = 0.0075). Syndecan-1 levels displayed satisfactory prognostic capability (AUC: 0.7056), whereas combining syndecan-1 and blood lactate demonstrated the highest predictive ability for 30-day survival (AUC: 0.7726)., Conclusions: Plasma syndecan-1 levels effectively predict sepsis prognosis, with higher baseline levels or increasing trends indicating worse outcomes. Combining syndecan-1 with blood lactate enhances predictive accuracy for 30-day mortality in sepsis., Trial Registration: This study registered in China on December 31, 2021 at Chinese Clinical Trial Registry (ChiCTR2100055066)., (© 2024 International Society of Surgery/Société Internationale de Chirurgie (ISS/SIC).)

In this study, we report a 42-year-old woman who was preoperatively diagnosed with uterine prolapse degree III. After full communication and signing the informed consent, the patient received transumbilical single-port laparoscopic sacrohysteropexy with the assistance of a robot under general anesthesia on January 11, 2024. Our hospital successfully performed the single-port robot-assisted transumbilical laparoscopic sacrohysteropexy in China, which confirms the safety and effectiveness of Jingfeng single port surgical robot system SP1000 in clinical application., (© 2025 International Federation of Gynecology and Obstetrics.)

Background and Purpose: Neurodegeneration is uneven in Parkinson's disease (PD). This study aimed to investigate spatiotemporal neurodegeneration in functional subregions of the substantia nigra (SN) and their connected cortex and subcortex in people with PD., Methods: A total of 120 patients with early-stage PD, 45 patients with advanced PD, and 120 healthy controls (HCs) were enrolled. The SN, cortex, and subcortex were divided into sensorimotor, associative, and limbic regions, respectively. Iron deposition in the SN was assessed by quantitative susceptibility mapping (QSM). Cortex and subcortex volumes were calculated based on T1-weighted imaging. Region of interest (ROI) analysis and voxel-based analysis (VBA) were performed to explore spatiotemporal neurodegeneration in patients with PD. p values were corrected for false discovery rate., Results: In the ROI analysis, the QSM values for the limbic (p = 0.018) and sensorimotor SN subregions (p = 0.018) were higher in PD patients than in HCs, but were not higher in the associative SN subregion (p = 0.295). In VBA, all SN functional subregions had clusters with higher QSM values in PD patients than in HCs (p < 0.001). The limbic SN subregion was the only one in which iron deposition increased from early-stage to advanced PD (p = 0.023). The QSM values of VBA&#95;limbic, sensorimotor, and associative SN had subregion-specific correlations with disease severity (p = 0.001 for the limbic and sensorimotor subregions, p = 0.003 for the associative subregion), motor symptoms (p = 0.057 for the limbic and sensorimotor subregion), and depression scores (p = 0.036 for the limbic subregion)., Conclusion: Iron deposition in SN functional subregions and atrophy of cortical and subcortical structures connected with the SN showed spatiotemporal selectivity. These findings reveal the potential pathogenesis of clinical heterogeneity in PD., (© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Objective: This study investigates the impact of Titin (TTN) gene mutations on radiotherapy sensitivity in rectum adenocarcinoma (READ) by examining changes in the tumour immune microenvironment., Methods: Data on gene expression and mutations in READ were obtained from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. Bioinformatics analysis explored the correlation between TTN mutations and immune cell infiltration. In vitro, lentiviral vectors were used to assess TTN mutations' effects on ANKRD1 expression in two READ cell lines. ANKRD1 was overexpressed, and clonogenic assays evaluated radiotherapy sensitivity. Flow cytometry, immunofluorescence, and comet assays examined mutations' impact on cell cycle, apoptosis, and DNA damage response (DDR). An in vivo mouse model and formalin-fixed paraffin-embedded samples from locally advanced rectal cancer (LARC) patients before and after radiotherapy were analyzed, followed by prognostic evaluation., Results: Bioinformatics revealed that TTN mutations increase radiation sensitivity in LARC by slowing cell proliferation, promoting apoptosis, and reducing DDR. TTN mutations also inhibit ANKRD1 expression via JUN disruption and enhance CD4/CD8 T-cell infiltration, improving anti-tumour immunity and outcomes. Observations from the clinical study showed a substantial decline in ANKRD1 expression levels alongside a notable surge in the counts of CD4 + and CD8 + T cells after undergoing radiotherapy. Patients with TTN mutations, low ANKRD1 expression, and high densities of CD4 + and CD8 + T cells had longer 3-year disease-free survival in READ., Conclusion: Our findings reveal that TTN mutations can serve as biomarkers for enhanced radiotherapy sensitivity in READ. By altering the tumour's immune microenvironment, these mutations may provide a novel target for personalized radiotherapy strategies, potentially improving therapeutic outcomes in patients with READ., Highlights: The association between TTN mutations and tumour mutation burden, as well as immune cell infiltration in READ, is examined. TTN mutations enhance the radiation sensitivity of READ cells and weaken DNA damage repair in response to radiation. TTN mutations increase the radiation sensitivity of READ cells by inhibiting ANKRD1. The infiltration of CD8 + and CD4 + T cells induced by TTN mutations is essential for anti-tumour immunity. TTN mutations serve as a biomarker for the pathological response to preoperative radiotherapy in READ., (© 2025 The Author(s). Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Background and Purpose: Glymphatic dysfunction may play a significant role in the development of neurodegenerative diseases. We aimed to evaluate the association between glymphatic dysfunction and the risk of malignant event/clinical milestones in Parkinson disease (PD)., Methods: This study included 236 patients from August 2014 to December 2020. Diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) index was calculated as an approximate measure of glymphatic function. The primary outcomes were four clinical milestones including recurrent falls, wheelchair dependence, dementia, and placement in residential or nursing home care. The associations of DTI-ALPS with the risk of clinical milestones were examined using multivariate Cox proportional hazards regression models. Then, logistic regression was repeated using clinical variables and DTI-ALPS index individually and in combination of the two to explore the ability to distinguish patients who reached clinical milestones within a 5-year period., Results: A total of 175 PD patients with baseline DTI-ALPS index and follow-up clinical assessments were included. A lower DTI-ALPS was independently associated with increased risk of recurrent falls, wheelchair dependence, and dementia. Additionally, in 103 patients monitored over 5 years, a logistic regression model combining clinical variables and DTI-ALPS index showed better performance for predicting wheelchair dependence within 5 years than a model using clinical variables or DTI-ALPS index alone., Conclusions: Glymphatic dysfunction, as measured by the DTI-ALPS index, was associated with increased risk of clinical milestones in patients with PD. This finding implies that therapy targeting the glymphatic system may serve as a viable strategy for slowing down the progression of PD., (© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Mass spectrometry imaging (MSI) technologies are widely used today to study the in situ spatial distributions for a variety of analytes. As these technologies advance, the pursuit of higher resolution in MSI has intensified. The limitation of direct desorption/ionization is its insufficient ionization, posing a constraint on the advancement of high-resolution MSI technologies. The introduction of postionization process compensates the low ionization efficiency caused by sacrificing the desorption area while pursuing high spatial resolution, resolving the conflict between high spatial resolution and high sensitivity in direct desorption/ionization method. Here, we discuss the sampling and ionization steps of MSI separately, and review the postionization methods in MSI according to three different sampling modes: laser sampling, probe sampling, and ion beam sampling. Postionization technology excels in enhancing ionization efficiency, boosting sensitivity, mitigating discrimination effect, simplifying sample preparation, and expanding the scope of applicability. These advantages position postionization technology as a promising tool for biomedical sciences, materials sciences, forensic analysis and other fields., (© 2024 John Wiley & Sons Ltd.)

Drug traffickers perform many crime strategies to avoid legal sanctions. The use of any crime strategy is mainly for reducing the risk of arrest, which has been the focus of research on restrictive deterrence. This study aims to develop a Restrictive Deterrence Utility Scale (RDUS) to measure the effectiveness of crime strategies used in drug trafficking. Survey data were collected from August to October 2021, including 294 female drug offenders aged between 21 and 61 years serving sentences with a median length of around 10 years in a Southern city in Mainland China. Exploratory and confirmatory factor analysis was conducted for scale investigation. Three valid and reliable factors for the RDUS were found: anomaly avoidance, reduction of exposure time, and the use of weapons and tools. Composite reliability, convergent validity, discriminant validity of three factors were confirmed with Cronbach α being higher than 0.9, that being higher than correspondent Average Variance Extracted which all being higher than 0.5 and higher than correspondent factor correlation. The RDUS offers a helpful method for assessing the motivation for drug traffickers to persist in drug crime and for formulating appropriate interventions for drug prohibition., (© 2023 The Authors. Journal of Community Psychology published by Wiley Periodicals LLC.)

A superhydrophobic surface is defined as having a contact angle exceeding 150 °C, indicating a remarkable ability to repel water. Generally, superhydrophobicity originates from the utilization of low-surface-energy materials with unique micro- and nanostructures. Superhydrophobic surfaces have gained considerable recognition and are widely employed in diverse areas for anti-icing, oil-water separation, anticorrosion, self-cleaning, blood-repellent, and antibacterial applications. These surfaces can greatly enhance industrial processes by yielding significant performance improvements. In this review, we introduce the basic theories that provide a foundation for understanding the hydrophobic properties of superhydrophobic surfaces. We then discuss current techniques for fabricating superhydrophobic coatings, critically analyzing their strengths and limitations. Furthermore, we provide an overview of recent progress in the application of superhydrophobic materials. Finally, we summarize the challenges in developing superhydrophobic materials and future trends in this field. The insights provided by this review can help researchers understand the basic knowledge of superhydrophobic surfaces and obtain the latest progress and challenges in the application of superhydrophobic surfaces. It provides help for further research and practical application of superhydrophobic surfaces., (© 2024 The Chemical Society of Japan and Wiley-VCH GmbH.)

Purpose: The role of lower hemoglobin A1c (HbA1c) variability in the effect of sodium glucose cotransporter-2 inhibitors (SGLT2i) on acute kidney injury (AKI) remains unclear. We compared AKI risk between SGLT2i and dipeptidyl peptidase 4 inhibitors (DPP4i) initiators. Additionally, we aimed to explore the extent to which SGLT2i's influence on AKI risk is mediated by reducing long-term HbA1c variability., Methods: Using 2018-2022 year data in Yinzhou Regional Health Care Database, we included adult, type 2 diabetes patients who were new users of SGLT2i or DPP4i. The effect of SGLT2i versus DPP4i on AKI, HbA1c variability, and AKI through HbA1c variability was compared using inverse probability of treatment weighted Cox proportional hazards models, median regression models, and causal mediation analysis., Results: With a median follow-up of 1.76 years, 19 717 adults (for SGLT2i, n = 6008; for DPP4i, n = 13 709) with type 2 diabetes were included. The adjusted hazard ratio for SGLT2i versus DPP4i was 0.79 (95% confidence interval [CI] 0.64-0.98) for AKI. The adjusted differences in median HbA1c variability score (HVS) and HbA1c reduction were -16.67% (95% CI: -27.71% to -5.62%) and -1.98% (95% CI: -14.34% to 10.38%), respectively. Furthermore, lower AKI risk associated with SGLT2i was moderately mediated (22.77%) through HVS. The results remained consistent across various subgroups and sensitivity analyses., Conclusions: Compared to DPP4i, lower AKI risk associated with SGLT2i is moderately mediated through HbA1c variability. These findings enhance our understanding of the effect of SGLT2i on AKI and underscore the importance of considering HbA1c variability in diabetes treatment and management., (© 2024 The Author(s). Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

Purpose: The purpose of this study is to evaluate the pattern, appropriateness, and cost of antidiabetic drugs prescribed for patients with Type 2 diabetes at primary healthcare facilities (PHFs) in China., Methods: We collected outpatient-visit prescriptions from 363 PHFs in 31 cities covering eastern, central, and western regions of China. The visits of adult patients with Type 2 diabetes diagnosis were collected and classified the antidiabetic medication pattern of each patient use as recommended or non-recommended according to Chinese guidelines. We then calculated the proportion of guideline-recommended patterns and the average monthly cost for each pattern, overall and by region., Results: Of 33 519 prescriptions for Type 2 diabetes, most (73.9%) were for guideline-recommended antidiabetic treatments. The proportion of guideline-recommended prescriptions varied by region (eastern [75.9%], central [87.5%], and western [59.7%]). Metformin monotherapy was the most common guideline-recommended treatment in all three regions (eastern [20.1%], central [28.0%], and western [24.6%]). The most common non-guideline-recommended treatments were monotherapy of insulin (eastern [16.5%], central [5.1%], and western [25.7%]) and traditional Chinese antidiabetic medicines (eastern [5.6%], central [5.7%], and western [11.1%]). The average monthly costs were lower for guideline-recommended treatments compared to non-recommended treatments in all regions (eastern [13.6 ± 15.4 USD vs. 28.1 ± 22.0 USD], central [9.8 ± 10.9 USD vs. 28.7 ± 19.4 USD], and western [17.9 ± 21.4 USD vs. 30.3 ± 23.6 USD])., Conclusions: The majority of patients with Type 2 diabetes received guideline-recommended antidiabetic medications at PHFs in China, with only half of the prescriptions containing guideline-recommended metformin. Utilization of guideline-recommended therapies differed across regions. Tailored interventions to promote evidence-based antidiabetic prescribing are urgently needed, especially in the undeveloped western region., (© 2024 John Wiley & Sons Ltd.)

Background: Although numerous studies have indicated that activated pyroptosis can enhance the efficacy of antitumour therapy in several tumours, the precise mechanism of pyroptosis in colorectal cancer (CRC) remains unclear., Methods: Pyroptosis in CRC cells treated with antitumour agents was assessed using various techniques, including Western blotting, lactate dehydrogenase release assay and microscopy analysis. To uncover the epigenetic mechanisms that regulate NLRP3, chromatin changes and NLRP3 promoter histone modifications were assessed using Assay for Transposase-Accessible Chromatin using sequencing and RNA sequencing. Chromatin immunoprecipitation‒quantitative polymerase chain reaction was used to investigate the NLRP3 transcriptional regulatory mechanism. Additionally, xenograft and patient-derived xenograft models were constructed to validate the effects of the drug combinations., Results: As the core molecule of the inflammasome, NLRP3 expression was silenced in CRC, thereby limiting gasdermin D (GSDMD)-mediated pyroptosis. Supplementation with NLRP3 can rescue pyroptosis induced by antitumour therapy. Overexpression of HDAC2 in CRC silences NLRP3 via epigenetic regulation. Mechanistically, HDAC2 suppressed chromatin accessibility by eliminating H3K27 acetylation. HDAC2 knockout promotes H3K27ac-mediated recruitment of the BRD4-p-P65 complex to enhance NLRP3 transcription. Inhibiting HDAC2 by Santacruzamate A in combination with classic antitumour agents (5-fluorouracil or regorafenib) in CRC xenograft-bearing animals markedly activated pyroptosis and achieved a significant therapeutic effect. Clinically, HDAC2 is inversely correlated with H3K27ac/p-P65/NLRP3 and is a prognostic factor for CRC patients., Conclusion: Collectively, our data revealed a crucial role for HDAC2 in inhibiting NLRP3/GSDMD-mediated pyroptosis in CRC cells and highlighted HDAC2 as a potential therapeutic target for antitumour therapy., Highlights: Silencing of NLRP3 limits the GSDMD-dependent pyroptosis in colorectal cancer. HDAC2-mediated histone deacetylation leads to epigenetic silencing of NLRP3. HDAC2 suppresses the NLRP3 transcription by inhibiting the formation of H3K27ac/BRD4/p-P65 complex. Targeting HDAC2 activates pyroptosis and enhances therapeutic effect., (© 2024 The Author(s). Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Objectives: Calcifying nanoparticles (CNPs), referred to as nanobacteria (NB), are recognized to be associated with ectopic calcification. This study aims to isolate and culture CNPs from the dental plaque of patients with periodontal disease and investigate their possible role in unravelling the aetiology of periodontal disease., Material and Methods: Supragingival and subgingival plaques were sampled from 30 periodontitis patients for CNPs isolation and culture. Alkaline phosphatase (ALP) content changes were tracked over time. Positive samples underwent thorough morphological identification via hematoxylin and eosin (HE) staining, Alizarin red S (ARS), and transmission electron microscopy (TEM). The chemical composition of CNPs analysis involved calcium (Ca) and phosphorus (P) content determination, Fourier transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD)., Results: The subgingival plaque dental group exhibited a higher CNPs isolation rate at 36.67% (11/30) compared to the supragingival dental plaque group at 66.67% (20/30). ALP activity varied among the positive, negative and control groups. Morphological observation characterized the CNPs as round, oval, and ellipsoid particles with Ca deposits. Chemical analysis revealed the Ca/P ratio was 0.6753. Hydroxyl, methyl, carbonate, phosphate, hydrogen phosphate, and dihydrogen phosphate were detected by FTIR; the main chemical components detected by XRD were hydroxyapatite and tricalcium phosphate., Conclusion: CNPs were found in periodontitis-related dental plaque and exhibited the potential to develop calcified structures resembling dental calculus. However, the potential involvement of ALP in CNPs formation requires deeper exploration, as does the precise nature of its role and the interrelation with periodontitis demand a further comprehensive investigation., (© 2024 The Authors. Clinical and Experimental Dental Research published by John Wiley & Sons Ltd.)

Background: To assess the feasibility of use of indocyanine green (ICG) in identifying and minimising urinary tract injury during surgical resection of endometriosis through robotic transvaginal natural orifice transluminal endoscopy surgery (RvNOTES)., Methods: We conducted a retrospective case series in two academic tertiary care hospitals. We examined 53 patients who underwent RvNOTES hysterectomy with planned endometriosis resection., Results: The study involved 53 patients undergoing RvNOTES with ICG fluorescence for endometriosis resection. Mean patient age was 37.98 ± 6.65 years. Operative time averaged 181.32 ± 53.94 min, with estimated blood loss at 45.57 ± 33.62 mL. Postoperative stay averaged 0.23 ± 0.47 days. No ICG-related complications occurred., Conclusion: No complications occurred with ICG fluorescence in RvNOTES. It appears to be a safe option for ureteral localisation and preservation. ICG fluorescence is widely used in diverse medical specialities for identifying ureters during complex surgeries. Larger studies are needed to firmly establish its advantages in intraoperative ureteral visualisation during RvNOTES for deep infiltrative endometriosis., (© 2024 John Wiley & Sons Ltd.)

We investigated the mechanism by which quercetin preserves mitochondrial quality control (MQC) in cardiomyocytes subjected to ischemia-reperfusion stress. An enzyme-linked immunosorbent assay was employed in the in vivo experiments to assess myocardial injury markers, measure the transcript levels of SIRT5/DNAPK-cs/MLKL during various time intervals of ischemia-reperfusion, and observe structural changes in cardiomyocytes using transmission electron microscopy. In in vitro investigations, adenovirus transfection was employed to establish a gene-modified model of DNA-PKcs, and primary cardiomyocytes were obtained from a mouse model with modified SIRT5 gene. Reverse transcription polymerase chain reaction, laser confocal microscopy, immunofluorescence localization, JC-1 fluorescence assay, Seahorse energy analysis, and various other assays were applied to corroborate the regulatory influence of quercetin on the MQC network in cardiomyocytes after ischemia-reperfusion. In vitro experiments demonstrated that ischemia-reperfusion injury caused changes in the structure of the myocardium. It was seen that quercetin had a beneficial effect on the myocardial tissue, providing protection. As the ischemia-reperfusion process continued, the levels of DNA-PKcs/SIRT5/MLKL transcripts were also found to change. In vitro investigations revealed that quercetin mitigated cardiomyocyte injury caused by mitochondrial oxidative stress through DNA-PKcs, and regulated mitophagy and mitochondrial kinetics to sustain optimal mitochondrial energy metabolism levels. Quercetin, through SIRT5 desuccinylation, modulated the stability of DNA-PKcs, and together they regulated the "mitophagy-unfolded protein response." This preserved the integrity of mitochondrial membrane and genome, mitochondrial dynamics, and mitochondrial energy metabolism. Quercetin may operate synergistically to oversee the regulation of mitophagy and the unfolded protein response through DNA-PKcs-SIRT5 interaction., (© 2024 John Wiley & Sons Ltd.)

Purpose: Widely used conventional 2D T 2 * approaches that are based on breath-held, electrocardiogram (ECG)-gated, multi-gradient-echo sequences are prone to motion artifacts in the presence of incomplete breath holding or arrhythmias, which is common in cardiac patients. To address these limitations, a 3D, non-ECG-gated, free-breathing T 2 * technique that enables rapid whole-heart coverage was developed and validated., Methods: A continuous random Gaussian 3D k-space sampling was implemented using a low-rank tensor framework for motion-resolved 3D T 2 * imaging. This approach was tested in healthy human volunteers and in swine before and after intravenous administration of ferumoxytol., Results: Spatial-resolution matched T 2 * images were acquired with 2-3-fold reduction in scan time using the proposed T 2 * mapping approach relative to conventional T 2 * mapping. Compared with the conventional approach, T 2 * images acquired with the proposed method demonstrated reduced off-resonance and flow artifacts, leading to higher image quality and lower coefficient of variation in T 2 *-weighted images of the myocardium of swine and humans. Mean myocardial T 2 * values determined using the proposed and conventional approaches were highly correlated and showed minimal bias., Conclusion: The proposed non-ECG-gated, free-breathing, 3D T 2 * imaging approach can be performed within 5 min or less. It can overcome critical image artifacts from undesirable cardiac and respiratory motion and bulk off-resonance shifts at the heart-lung interface. The proposed approach is expected to facilitate faster and improved cardiac T 2 * mapping in those with limited breath-holding capacity or arrhythmias., (© 2024 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Subcutaneous (s.c.) administration of monoclonal antibodies (mAbs) can reduce treatment burden for patients and healthcare systems compared with intravenous (i.v.) infusion through shorter administration times, made possible by convenient, patient-centric devices. A deeper understanding of clinical pharmacology principles related to efficacy and safety of s.c.-administered mAbs over the past decade has streamlined s.c. product development. This review presents learnings from key constituents of the s.c. mAb development pathway, including pharmacology, administration variables, immunogenicity, and delivery devices. Restricted mAb transportation through the hypodermis explains their incomplete absorption at a relatively slow rate (pharmacokinetic (PK)) and may impact mAb-cellular interactions and/or onset and magnitude of physiological responses (pharmacodynamic). Injection volumes, formulation, rate and site of injection, and needle attributes may affect PKs and the occurrence/severity of adverse events like injection-site reactions or pain, with important consequences for treatment adherence. A review of immunogenicity data for numerous compounds reveals that incidence of anti-drug antibodies (ADAs) is generally comparable across i.v. and s.c. routes, and complementary factors including response magnitude (ADA titer), persistence over time, and neutralizing antibody presence are needed to assess clinical impact. Finally, four case studies showcase how s.c. biologics have been clinically developed: (i) by implementation of i.v./s.c. bridging strategies to streamline PD-1/PD-L1 inhibitor development, (ii) through co-development with i.v. presentations for anti-severe acute respiratory syndrome-coronavirus 2 antibodies to support rapid deployment of both formulations, (iii) as the lead route for bispecific T cell engagers (BTCEs) to mitigate BTCE-mediated cytokine release syndrome, and (iv) for pediatric patients in the case of dupilumab., (© 2023 Regeneron Pharmaceuticals Inc. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Background and Purpose: Atherosclerosis induced by cyclosporine A (CsA), an inhibitor of the calcineurin/nuclear factor of activated T cells (NFAT) pathway, is a major concern after organ transplantation. However, the atherosclerotic mechanisms of CsA remain obscure. We previously demonstrated that calcineurin/NFAT signalling inhibition contributes to atherogenesis via suppressing microRNA-204 (miR-204) transcription. We therefore hypothesised that miR-204 is involved in the development of CsA-induced atherosclerosis., Experimental Approach: ApoE -/- mice with macrophage-miR-204 overexpression were generated to determine the effects of miR-204 on CsA-induced atherosclerosis. Luciferase reporter assays and chromatin immunoprecipitation sequencing were performed to explore the targets mediating miR-204 effects., Key Results: CsA alone did not significantly affect atherosclerotic lesions or serum lipid levels. However, it exacerbated high-fat diet-induced atherosclerosis and hyperlipidemia in C57BL/6J and ApoE -/- mice, respectively. miR-204 levels decreased in circulating monocytes and plaque lesions during CsA-induced atherosclerosis. The upregulation of miR-204 in macrophages inhibited CsA-induced atherosclerotic plaque formation but did not affect serum lipid levels. miR-204 limited the CsA-induced foam cell formation by reducing the expression of the scavenger receptors SR-BII and CD36. SR-BII was post-transcriptionally regulated by mature miR-204-5p via 3'-UTR targeting. Additionally, nuclear-localised miR-204-3p prevented the CsA-induced binding of Ago2 to the CD36 promoter, suppressing CD36 transcription. SR-BII or CD36 expression restoration dampened the beneficial effects of miR-204 on CsA-induced atherosclerosis., Conclusion and Implications: Macrophage miR-204 ameliorates CsA-induced atherosclerosis, suggesting that miR-204 may be a potential target for the prevention and treatment of CsA-related atherosclerotic side effects., (© 2023 British Pharmacological Society.)

Background and Purpose: The specific pathophysiological mechanisms underlying postural instability/gait difficulty (PIGD) and cognitive function in Parkinson's disease (PD) remain unclear. Both postural and gait control, as well as cognitive function, are associated with the cholinergic basal forebrain (cBF) system., Methods: A total of 84 PD patients and 82 normal controls were enrolled. Each participant underwent motor and cognitive assessments. Diffusion tensor imaging was used to detect structural abnormalities in the cBF system. The cBF was segmented using FreeSurfer, and its fiber tract was traced using probabilistic tractography. To provide information on extracellular water accumulation, free-water fraction (FWf) was quantified. FWf in the cBF and its fiber tract, as well as cortical projection density, were extracted for statistical analyses., Results: Patients had significantly higher FWf in the cBF (p < 0.001) and fiber tract (p = 0.021) than normal controls, as well as significantly lower cBF projection in the occipital (p < 0.001), parietal (p < 0.001) and prefrontal cortex (p = 0.005). In patients, a higher FWf in the cBF correlated with worse PIGD score (r = 0.306, p = 0.006) and longer Trail Making Test A time (r = 0.303, p = 0.007). Attentional function (Trail Making Test A) partially mediated the association between FWf in the cBF and PIGD score (indirect effect, a*b = 0.071; total effect, c = 0.256; p = 0.006)., Conclusions: Our findings suggest that degeneration of the cBF system in PD, from the cBF to its fiber tract and cortical projection, plays an important role in cognitive-motor interaction., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

The evolution of magnetic susceptibility of the brain is mainly determined by myelin in white matter (WM) and iron deposition in deep gray matter (DGM). However, existing imaging techniques have limited abilities to simultaneously quantify the myelination and iron deposition within a voxel throughout brain development and aging. For instance, the temporal trajectories of iron in the brain WM and myelination in DGM have not been investigated during the aging process. This study aimed to map the age-related iron and myelin changes in the whole brain, encompassing myelin in DGM and iron deposition in WM, using a novel sub-voxel quantitative susceptibility mapping (QSM) method. To achieve this, a cohort of 494 healthy adults (18-80 years old) was studied. The sub-voxel QSM method was employed to obtain the paramagnetic and diamagnetic susceptibility based on the approximated R 2 ' map from acquired R 2 * map. The linear relationship between R 2 * and R 2 ' maps was established from the regression coefficients on a small cohort data acquired with both 3D gradient recalled echo data and R 2 mapping. Large cohort sub-voxel susceptibility maps were used to create longitudinal and age-specific atlases via group-wise registration. To explore the differential developmental trajectories in the DGM and WM, we employed nonlinear models including exponential and Poisson functions, along with generalized additive models. The constructed atlases reveal the iron accumulation in the posterior part of the putamen and the gradual myelination process in the globus pallidus with aging. Interestingly, the developmental trajectories show that the rate of myelination differs among various DGM regions. Furthermore, the process of myelin synthesis is paralleled by an associated pattern of iron accumulation in the primary WM fiber bundles. In summary, our study offers significant insights into the distinctive developmental trajectories of iron in the brain's WM and myelination/demyelination in the DGM in vivo. These findings highlight the potential of using sub-voxel QSM to uncover new perspectives in neuroscience and improve our understanding of whole-brain myelination and iron deposit processes across the lifespan., (© 2023 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Aloe-emodin (AE) has been shown to inhibit the proliferation of several cancer cell lines, including human nasopharyngeal carcinoma (NPC) cell lines. In this study, we confirmed that AE inhibited malignant biological behaviors, including cell viability, abnormal proliferation, apoptosis, and migration of NPC cells. Western blotting analysis revealed that AE upregulated the expression of DUSP1, an endogenous inhibitor of multiple cancer-associated signaling pathways, resulting in blockage of the extracellular signal-regulated kinase (ERK)-1/2, protein kinase B (AKT), and p38-mitogen activated protein kinase（p38-MAPK） signaling pathways in NPC cell lines. Moreover, the selective inhibitor of DUSP1, BCI-hydrochloride, partially reversed the AE-induced cytotoxicity and blocked the aforementioned signaling pathways in NPC cells. In addition, the binding between AE and DUSP1 was predicted via molecular docking analysis using AutoDock-Vina software and further verified via a microscale thermophoresis assay. The binding amino acid residues were adjacent to the predicted ubiquitination site (Lys192) of DUSP1. Immunoprecipitation with the ubiquitin antibody, ubiquitinated DUSP1 was shown to be upregulated by AE. Our findings revealed that AE can stabilize DUSP1 by blocking its ubiquitin-proteasome-mediated degradation and proposed an underlying mechanism by which AE-upregulated DUSP1 may potentially target multiple pathways in NPC cells., (© 2023 John Wiley & Sons Ltd.)

Dopamine replacement therapy (DRT) represents the standard treatment for Parkinson's disease (PD), however, instant and long-term medication influence on patients' brain function have not been delineated. Here, a total of 97 drug-naïve patients, 43 patients under long-term DRT, and 94 normal control (NC) were, retrospectively, enrolled. Resting-state functional magnetic resonance imaging data and motor symptom assessments were conducted before and after levodopa challenge test. Whole-brain functional connectivity (FC) matrices were constructed. Network-based statistics were performed to assess FC difference between drug-naïve patients and NC, and these significant FCs were defined as disease-related connectomes, which were used for further statistical analyses. Patients showed better motor performances after both long-term DRT and levodopa challenge test. Two disease-related connectomes were observed with distinct patterns. The FC of the increased connectome, which mainly consisted of the motor, visual, subcortical, and cerebellum networks, was higher in drug-naïve patients than that in NC and was normalized after long-term DRT (p-value <.050). The decreased connectome was mainly composed of the motor, medial frontal, and salience networks and showed significantly lower FC in all patients than NC (p-value <.050). The global FC of both increased and decreased connectome was significantly enhanced after levodopa challenge test (q-value <0.050, false discovery rate-corrected). The global FC of increased connectome in ON-state was negatively associated with levodopa equivalency dose (r = -.496, q-value = 0.007). Higher global FC of the decreased connectome was related to better motor performances (r = -.310, q-value = 0.022). Our findings provided insights into brain functional alterations under dopaminergic medication and its benefit on motor symptoms., (© 2023 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

The pedunculopontine nucleus (PPN) is a small brainstem structure and has attracted attention as a potentially effective deep brain stimulation (DBS) target for the treatment of Parkinson's disease (PD). However, the in vivo location of PPN remains poorly described and barely visible on conventional structural magnetic resonance (MR) images due to a lack of high spatial resolution and tissue contrast. This study aims to delineate the PPN on a high-resolution (HR) atlas and investigate the visibility of the PPN in individual quantitative susceptibility mapping (QSM) images. We combine a recently constructed Montreal Neurological Institute (MNI) space unbiased QSM atlas (MuSus-100), with an implicit representation-based self-supervised image super-resolution (SR) technique to achieve an atlas with improved spatial resolution. Then guided by a myelin staining histology human brain atlas, we localize and delineate PPN on the atlas with improved resolution. Furthermore, we examine the feasibility of directly identifying the approximate PPN location on the 3.0-T individual QSM MR images. The proposed SR network produces atlas images with four times the higher spatial resolution (from 1 to 0.25 mm isotropic) without a training dataset. The SR process also reduces artifacts and keeps superb image contrast for further delineating small deep brain nuclei, such as PPN. Using the myelin staining histological atlas as guidance, we first identify and annotate the location of PPN on the T1-weighted (T1w)-QSM hybrid MR atlas with improved resolution in the MNI space. Then, we relocate and validate that the optimal targeting site for PPN-DBS is at the middle-to-caudal part of PPN on our atlas. Furthermore, we confirm that the PPN region can be identified in a set of individual QSM images of 10 patients with PD and 10 healthy young adults. The contrast ratios of the PPN to its adjacent structure, namely the medial lemniscus, on images of different modalities indicate that QSM substantially improves the visibility of the PPN both in the atlas and individual images. Our findings indicate that the proposed SR network is an efficient tool for small-size brain nucleus identification. HR QSM is promising for improving the visibility of the PPN. The PPN can be directly identified on the individual QSM images acquired at the 3.0-T MR scanners, facilitating a direct targeting of PPN for DBS surgery., (© 2023 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Background: Mounting evidence have indicated that long noncoding RNA (lncRNA) muscleblind like splicing regulator 1 antisense RNA 1 (MBNL1-AS1) play a crucial regulatory role in cardiovascular disease, myocardial infarction (MI) included. In this research, we sought to probe into the biological function and potential mechanism of MBNL1-AS1 in MI., Methods: Cardiomyocytes were treated under hypoxic conditions for 0-12 h. Functional assays including CCK-8 and flow cytometry were performed to assess hypoxia-stimulated cardiomyocyte viability and apoptosis, respectively. Moreover, bioinformatics analysis and mechanical assays were conducted to reveal the competitive endogenous RNA (ceRNA) mechanism of MBNL1-AS1., Results: The upregulation of MBNL1-AS1 was found in hypoxia-stimulated cardiomyocytes. Functionally, the downregulation of MBNL1-AS1 dramatically promoted hypoxia-induced cardiomyocyte viability and inhibited apoptosis. Mechanistically, miR-132-3p bound to MBNL1-AS1 in hypoxia-induced cardiomyocytes, and miR-132-3p directly targeted RAB14, member RAS oncogene family (RAB14) and calmodulin binding transcription activator 1 (CAMTA1). Furthermore, MBNL1-AS1 upregulates the expression of RAB14 and CAMTA1 in hypoxia-stimulated cardiomyocytes via targeting miR-132-3p., Conclusions: The current study revealed the critical role of the MBNL1-AS1/miR-132-3p/RAB14/CAMTA1 axis in MI, indicating MBNL1-AS1 as an innovative therapeutic target for MI., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Yanbing Li et al.)

Purpose: To improve susceptibility tensor imaging (STI) reconstruction using the asymmetric STI model with the correction of non-bulk-magnetic-susceptibility (NBMS) effects., Method: A frequency offset term was introduced into the asymmetric STI model to account for the bias between measured MRI frequency signals and conventional susceptibility tensor models because of NBMS contributions. Experiments were conducted to compare the proposed model with conventional STI, conventional STI with the proposed frequency offset correction, and asymmetric STI on simulation, ex vivo mouse brain, and in vivo human brain data., Results: In the simulation where NBMS contributions are head rotation-invariant, the proposed method achieves the lowest errors in mean magnetic susceptibility (MMS) and magnetic susceptibility anisotropy (MSA) and is more robust to noise in the estimation of principal eigenvector (PEV). When considering the head orientation dependency of NBMS contributions, the proposed method shows advantages in estimating MSA and PEV. On the mouse and human brain data, the proposed method produces more reliable MSA maps and more consistent white matter fiber directions when referring to those from DTI than the compared STI methods., Conclusion: The proposed method can reduce the effects of NBMS-related frequency shifts on the susceptibility tensors in the brain white matter. This study inspires STI reconstruction from the perspective of better modeling the sources of frequency shifts., (© 2022 International Society for Magnetic Resonance in Medicine.)

Diabetic wound is one of the most severe complications of diabetes mellitus (DM). Despite the associated risks of wound healing impairment in diabetes, treatment strategies remain limited. Yeliangen (YLG) is a Chinese formulation mainly composed of the rhizome of Coptis chinensis , the root of Isatis tinctoria , and the leaf of Isatis indigotica . We investigated the wound healing effects of YLG in type 2 diabetic (T2DM) rats, which were induced by intraperitoneal administration of streptozotocin after a high-fat diet for four weeks. 3 × 3 cm 2 full-thickness excisional wounds were created on the dorsal surface of rats and then divided to control (DC), negative (DPJ), positive (DPC), and YLG-treated (DYLG) groups. Rat's wounds were treated twice daily for 21 days. Wound area and wound contraction were detected on days 0, 3, 7, 14, and 21. Histopathological examinations were performed by H&E staining and immunohistochemistry (IHC). The biochemical parameters, mRNAs, and protein expressions were analyzed through enzyme-linked immunoassays (ELISA), qPCR, and western blot, respectively. Compared with other groups, the histological changes of wound tissue in the DYLG group were improved, and the expressions of CD31, eNOS, and PCNA were significantly upregulated. Besides, YLG significantly reduced the inflammatory factors' expressions of TNF- α , NF- κ B, MMP-9, and IL-1B on days 7, 14, and 21 postwounding. Moreover, YLG induced angiogenesis and neovascularization by significantly increasing the levels of VEGF, TGF- β 1, EGF, PDGF, and SDF-1 α on days 3, 7, and 14. In conclusion, YLG improved wound healing by reducing inflammation and increasing angiogenesis which may provide an alternative and effective approach for diabetic wound therapy., Competing Interests: All authors declare that there are no conflict of interest regarding the publication of this paper., (Copyright © 2022 Abdulbaset Al-Romaima et al.)

This umbrella review is to recapitulate and grade the available evidence of associations between consumption of Zingiberaceae plants/curcumin (Cur) and multiple health-related outcomes. This study included 161 meta-analyses of randomized controlled trials in 76 articles with 67 unique health outcomes. Data on heterogeneity and publication bias are considered to assess the quality of evidence. Based on the different impact of Zingiberaceae plants/Cur on human health, the advantages outweigh the disadvantages. Zingiberaceae plants/Cur can mainly improve metabolic syndrome, non-alcoholic fatty liver disease, cardiovascular disease, and some chronic inflammatory diseases, likewise, obviously relief the pain of osteoarthritis and related diseases. Ginger supplements have been shown to improve vomiting during pregnancy and to relieve nausea and vomiting caused by chemotherapy and surgery. The surgery is any type of surgery, including laparoscopic surgery, gynecological surgery and mixed surgery. Beneficial associations were found with Cur intervention in gastrointestinal, neurological and oral diseases. Zingiberaceae plants/Cur are generally safe and favorable for multiple health outcomes in humans. High-quality research is further needed to prove the observed associations., (© 2022 John Wiley & Sons Ltd.)