Melatonin mitigates PNMC-induced disruption of spindle assembly and mitochondrial function in mouse Oocytes.

3-methyl-4-nitrophenol (PNMC), a degradation product of organophosphorus insecticides and a byproduct of fuel combustion, exerting endocrine-disrupting effects. However, its impact on the meiotic process of oocytes remains unclear. In the present study, we investigated the effects of PNMC on meiotic maturation of mouse oocytes in vitro and related mechanisms. Morphologically, PNMC-exposure affected germinal vesicle breakdown (GVBD) and polar body extrusion (PBE) in mouse oocytes. Proteomic analysis suggested that PNMC-exposure altered oocyte protein expression that are associated with cytoskeleton, mitochondrial function and oxidative stress. Further studies demonstrated that PNMC-exposure disrupted spindle assembly and chromosome alignment, caused sustained activation of spindle assembly checkpoint (SAC), and arrested meiosis in oocytes. Specifically, PNMC-exposure interfered with the function of microtubule organizing centers (MTOCs) by significantly reducing phosphorylated mitogen activated protein kinase (p-MAPK) expression and disrupting the localization of Pericentrin and p-Aurora A, leading to spindle assembly failure. Besides, PNMC-exposure also increased α-tubulin acetylation, decreased microtubule stability. Moreover, PNMC-exposure impaired mitochondrial function, evidenced by abnormal mitochondrial distribution, decreased mitochondrial membrane potential and ATP levels, release of Cytochrome C into the cytoplasm, and elevated ROS levels. As a result, exposure to PNMC caused DNA damage and early apoptosis in oocytes. Fortunately, melatonin was able to promote oocyte maturation by removing the excessive ROS and enhancing mitochondrial function. These results highlight the adverse effects of PNMC on meiotic maturation, and underscore the protective role of melatonin against PNMC-induced damage.

Ultrasound assessment of diaphragmatic dysfunction in non-critically ill patients: relevant indicators and update.

Diaphragm dysfunction (DD) can be classified as mild, resulting in diaphragmatic weakness, or severe, resulting in diaphragmatic paralysis. Various factors such as prolonged mechanical ventilation, surgical trauma, and inflammation can cause diaphragmatic injury, leading to negative outcomes for patients, including extended bed rest and increased risk of pulmonary complications. Therefore, it is crucial to protect and monitor diaphragmatic function. Impaired diaphragmatic function directly impacts ventilation, as the diaphragm is the primary muscle involved in inhalation. Even unilateral DD can cause ventilation abnormalities, which in turn lead to impaired gas exchange, this makes weaning from mechanical ventilation challenging and contributes to a higher incidence of ventilator-induced diaphragm dysfunction and prolonged ICU stays. However, there is insufficient research on DD in non-ICU patients, and DD can occur in all phases of the perioperative period. Furthermore, the current literature lacks standardized ultrasound indicators and diagnostic criteria for assessing diaphragmatic dysfunction. As a result, the full potential of diaphragmatic ultrasound parameters in quickly and accurately assessing diaphragmatic function and guiding diagnostic and therapeutic decisions has not been realized.

Comprehensive analysis of the oral microbiota and metabolome change in patients of burning mouth syndrome with psychiatric symptoms.

Background: Burning mouth syndrome (BMS) is a chronic idiopathic facial pain with intraoral burning or dysesthesia. BMS patients regularly suffer from anxiety/depression, and the association of psychiatric symptoms with BMS has received considerable attention in recent years. The aims of this study were to investigate the potential interplay between psychiatric symptoms and BMS. Methods: Using 16S rRNA sequencing and liquid chromatography-mass spectrometry (LC/MS) to evaluate the oral microbiota and saliva metabolism of 40 BMS patients [including 29 BMS patients with depression or anxiety symptoms (DBMS)] and 40 age matched healthy control (HC). Results: The oral microbiota composition in BMS exhibited no significant differences from HC, although DBMS manifested decreased α-diversity relative to HC. Noteworthy was the discernible elevation in the abundance of proinflammatory microorganisms within the oral microbiome of individuals with DBMS. Parallel findings in LC/MS analyses revealed discernible disparities in metabolites between DBMS and HC groups. Principal differential metabolites were notably enriched in amino acid metabolism and lipid metabolism, exhibiting associations with infectious and immunological diseases. Furthermore, the integrated analysis underscores a definitive association between the oral microbiome and metabolism in DBMS. Conclusions: This study suggests possible future modalities for better understanding the pathogenesis and personalized treatment plans of BMS.

Effectiveness and safety of tripterygium wilfordii poly-glycosides on glomerulonephritis: a systematic review and meta-analysis.

Treatment of glomerulonephritis presents several challenges, including limited therapeutic options, high costs, and potential adverse reactions. As a recognized Chinese patent medicine, Tripterygium wilfordii poly-glycosides (TWP) have shown promising benefits in managing autoimmune diseases. To evaluate clinical effectiveness and safety of TWP in treating glomerulonephritis, we systematically searched PubMed, Cochrane Library, Web of Science, and Embase databases for controlled studies published up to 12 July 2023. We employed weighted mean difference and relative risk to analyze continuous and dichotomous outcomes. This meta-analysis included 16 studies that included primary membranous nephropathy (PMN), type 2 diabetic kidney disease (DKD), and Henoch-Schönlein purpura nephritis (HSPN). Analysis revealed that additional TWP administration improved patients' outcomes and total remission rates, reduced 24-h urine protein (24hUP) and decreased relapse events. The pooled results demonstrated the non-inferiority of TWP to glucocorticoids in achieving total remission, reducing 24hUP, and converting the phospholipase A2 receptor (PLA2R) status to negative. For DKD patients, TWP effectively reduced 24hUP levels, although it did not significantly improve the estimated glomerular filtration rate (eGFR). Compared to valsartan, TWP showed comparable improvements in 24hUP and eGFR levels. In severe cases of HSPN in children, significant clinical remission and a reduction in 24hUP levels were observed with the addition of TWP treatment. TWP did not significantly increase the incidence of adverse reactions. Therefore, TWP could offer therapeutic benefits to patients with PMN, DKD, and severe HSPN, with a minimal increase in the risk of side effects.

Real-imaginary spectrum decomposition of the transparency spectra in microwave dressed Rydberg systems.

To distinguish the contributions of electromagnetically induced transparency (EIT) and Autler-Townes splitting (ATS) in their applications in precision laser spectroscopy, we propose a real-imaginary spectrum decomposition method to investigate the transparency spectra in a four-level microwave (MW) dressed Rydberg system. We show that the opening transparency windows in the absorption spectra of probe field is a prominent character by EIT, EIT-ATS crossover, and ATS when the MW field is turned off and the intensity of the control field is adjusted. When the MW field is turned on and gradually increased, the EIT is destroyed and disappears. In addition, the most prominent characters that open a transparency window are the EIT-ATS crossover and the ATS. Then, if we further increase the intensity of the MW field, we find that the transparency windows open mainly due to the ATS. Compared to the previous considerations of this issue, which were limited to three-level systems, our four-level scheme reported here is useful for understanding the features of quantum interference in multilevel atomic systems, and has potential applications to study enhanced sensitivity, measurement spectroscopic, quantum processing, quantum communication, and transmission.

PCSK9 expression in fibrous cap possesses a marker for rupture in advanced plaque.

BACKGROUND: To date, PCSK9 inhibitors are well known for eliminating cardiac and cerebral artery ischemia events by lowering the serum lipid level. However, the pathophysiological value of in-plaque PCSK9 expression is still unclear. METHODS: Advanced plaques removed by carotid endarterectomy were sectioned and stained to identify the PCSK9 expression pattern and its co-expression with rupture-relevant markers. To investigate the correlation of PCSK9 expression with regional blood shear flow, hemodynamic characteristics were analyzed using computational fluid dynamics, and representative parameters were compared between PCSK9 positive and negative staining plaques. To explore this phenomenon in vitro, human aortic vascular smooth muscle cells were used to overexpress and knock down PCSK9. The impacts of PCSK9 modulations on mechanical sensor activity were testified by western blot and immunofluorescence. Real-time polymerase chain reaction was used to evaluate the transcription levels of downstream rupture-prone effectors. RESULTS: PCSK9 distribution in plaque preferred cap and shoulder regions, residing predominantly in smooth muscle actin-positive cells. Cap PCSK9 expression correlated with fibrous cap thickness negatively and co-expressed with MMP-9, both pointing to the direction of plaque rupture. A hemodynamic profile indicated a rupture-prone feature of cap PCSK9 expression. In vitro, overexpression and knockdown of PCSK9 in human aortic vascular smooth muscle cells has positive modulation on mechanical sensor Yes-associated protein 1 (YAP) activity and transcription levels of its downstream rupture-prone effectors. Serial section staining verified in situ colocalization among PCSK9, YAP, and downstream effectors. CONCLUSIONS: Cap PCSK9 possesses a biomarker for rupture risk, and its modulation may lead to a novel biomechanical angle for plaque interventions.

Proactive health behavior in middle-aged and older adult females with urinary incontinence: A grounded theory study.

AIM: To develop a conceptual framework for proactive health behavior among middle-aged and older adult females with urinary incontinence. DESIGN: Qualitative grounded theory study. BACKGROUND: There is a growing body of research emphasizing the pivotal significance of proactive health behavior. Proactive health behavior can empower patients to actively manage their illnesses and facilitate disease recovery. Clearly defining patients' relevant beliefs and assumptions regarding proactive health behavior can effectively promote their adoption. However, there is currently a lack of relevant research in this area. METHODS: We conducted in-depth interviews with middle-aged and older adult females with urinary incontinence (n = 17) and nursing caregivers (n = 9). We used theoretical sampling, whlie conducting continuous comparative analysisi and data collection. RESULTS: The study has yielded a substantive theory to facilitate healthcare professionals' comprehension of proactive health behavior in middle-aged and older adult females with urinary incontinence. The foundation for middle-aged and older adult females to adopt proactive health behavior is having a certain level of health literacy regarding their conditions. Patients' internal motivation to engage in proactive health behavior includes a sense of health responsibility and health demands. Additionally, external support received by patients can also facilitate their adoption of proactive health behavior. The proactive health behavior practices of middle-aged and older adult females mainly include proactive medical care behavior and establishing a healthy lifestyle. CONCLUSIONS: The conceptual framework established in this study offers theoretical support for middle-aged and older adult females with urinary incontinence to adopt proactive health behavior. It provides a basis for future exploration of proactive health behavior among this demographic and informs the development of more effective health interventions and support measures tailored to their needs. IMPACT: The study specifically elucidates the mechanisms and manifestations of proactive health behavior adopted by middle-aged and older adult females with urinary incontinence, laying the foundation for clarifying the level of proactive health among patients and implementing corresponding intervention measures. Additionally, it can also serve as a reference for related research on other diseases.

Oral oxytocin blurs sex differences in amygdala responses to emotional scenes.

BACKGROUND: The sex differences were co-shaped by innate biological differences and social environment, and were frequently observed in human emotional neural responses. Oral administration of oxytocin, as an alternative and noninvasive intake method, has been demonstrated to produce sex-dependent effects on emotional face processing. However, it is unclear whether oral oxytocin produces similar sex-dependent effects on processing continuous emotional scenes. METHODS: Current randomized, double-blind, placebo-controlled neuro-psychopharmacological fMRI experiment was conducted in 147 healthy participants (oxytocin=74, male/female=37/37; placebo=73, male/female=36/37) to examine the oral oxytocin effect on plasma oxytocin concentrations and neural response to emotional scenes in both sexes. RESULTS: At the neuroendocrine level, females showed lower endogenous oxytocin concentrations than males, but oral oxytocin equally increased the oxytocin concentrations in both sexes. Regarding neural activity, emotional scenes evoked opposite valence-independent effects on right amygdala activation (females>males) and its functional connectivity with the insula (males>females) in two sexes in the placebo group. This sex difference were either attenuated (amygdala response) or even completely eliminated (amygdala-insula functional connectivity) in the oxytocin group. The multivariate pattern analysis confirmed these findings by developing an accurate sex-predictive neural pattern that including the amygdala and the insula under the placebo but not oxytocin condition. CONCLUSION: Present study suggests a pronounced sex-difference in neural responses to emotional scenes which is abolished by oral oxytocin, with it having opposite modulatory effects in two sexes. Possibly this may reflect oral OXT enhancing emotional regulation to continuous emotional stimuli in both sexes by facilitating appropriate changes in sex-specific amygdala-insula circuitry.

Changes in blood catecholamines during induction of general anesthesia in patients with post-induction hypotension undergoing laparoscopic cholecystectomy: A single-center prospective cohort study.

BACKGROUND: Post-induction hypotension (PIH) often occurs during general anesthesia induction. This study aimed to investigate blood catecholamine levels during induction of general anesthesia in patients with PIH undergoing laparoscopic cholecystectomy. METHODS: This prospective study included 557 adult patients who underwent laparoscopic cholecystectomy under general anesthesia. PIH was defined as a greater than 20% decrease in systolic blood pressure from the pre-induction value, a systolic arterial pressure of less than 90 mmHg, or both. Plasma concentrations of epinephrine and norepinephrine during the induction of general anesthesia were determined using enzyme-linked immunosorbent assay. Multivariate logistic regression analysis evaluated the association between the clinical factors and PIH. RESULTS: Of the 557 patients, 390 had PIH, and the remaining 167 were allocated to the non-PIH group. Changes in blood adrenaline, noradrenaline levels, or both were more pronounced in the PIH than in the non-PIH group (p<0.05). Age, body mass index, a history of hypertension, preoperative systolic blood pressure, and propofol or sufentanil dose were independent predictors of PIH. CONCLUSION: The changes of blood catecholamines in patients with more stable hemodynamics during the induction of general anesthesia are smaller than that in patients with post-induction hypotension. TRIAL REGISTRATION: ChiCTR2200055549, 12/01/2022.

Growth of 1D Carbon Nanotube@Perovskite Core-Shell van der Waals Heterostructures through Chemical Vapor Deposition.

Perovskite is an emerging material with immense potential in the field of optoelectronics. 1D perovskite nanowires are crucial building blocks for the development of optoelectronic devices. However, producing perovskite nanowires with high quality and controlled alignment is challenging. In this study, the direct epitaxial growth of perovskite on oriented carbon nanotube (CNT) templates is presented through a chemical vapor deposition method. The deposition process of lead iodide and methylammonium iodide is systematically investigated, and a layer plus island growth mechanism is proposed to interpret the experimental observations. The aligned long CNTs serve as 1D templates and allow the growth of CNT@perovskite core-shell heterostructure with a high aspect ratio to withstand large deformation. The obtained 1D perovskite materials can be easily manipulated and transferred, enabling the facile preparation of microscale flexible devices. For proof of concept, a photodetector based on an individual CNT@methylammonium lead iodide heterostructure is fabricated. This work provides a new approach to prepare 1D hetero-nanostructure and may inspire the design of novel flexible nanophotodetectors.

Sirtuin 5-driven meiotic spindle assembly and actin-based migration in mouse oocyte meiosis.

Sirtuin 5 (Sirt5), a member of the Sirtuin family, is involved in various intracellular biological processes. However, the function of Sirt5 in oocyte maturation has not been clearly elucidated. In this study, we observed that Sirt5 was persistently expressed during the meiotic division of mouse oocytes, with a notable decline in expression in aging oocytes. Sirt5 inhibition led to the failure of the first polar body extrusion and induced cell cycle arrest, indicative of unsuccessful oocyte maturation. Furthermore, Sirt5 inhibition was associated with the extrusion of abnormally large polar bodies, suggesting disrupted asymmetric oocyte division. Mechanistically, the inhibition of Sirt5 resulted in aberrant spindle assembly and disordered chromosome alignment in oocytes. Moreover, Sirt5 inhibition caused the spindle to be centrally located in the oocyte without migrating to the cortical region, consequently preventing the formation of the actin cap. Further investigation revealed that Sirt5 inhibition notably diminished the expression of phosphorylated cofilin and profilin1, while increasing cytoplasmic F-actin levels. These findings suggest that Sirt5 inhibition during oocyte maturation adversely affects spindle assembly and chromosome alignment and disrupts actin dynamics impairing spindle migration and contributing to the failure of symmetric oocyte division and maturation.

Kidney Aging and Chronic Kidney Disease.

The process of aging inevitably leads to an increase in age-related comorbidities, including chronic kidney disease (CKD). In many aspects, CKD can be considered a state of accelerated and premature aging. Aging kidney and CKD have numerous common characteristic features, ranging from pathological presentation and clinical manifestation to underlying mechanisms. The shared mechanisms underlying the process of kidney aging and the development of CKD include the increase in cellular senescence, the decrease in autophagy, mitochondrial dysfunction, and the alterations of epigenetic regulation, suggesting the existence of potential therapeutic targets that are applicable to both conditions. In this review, we provide a comprehensive overview of the common characteristics between aging kidney and CKD, encompassing morphological changes, functional alterations, and recent advancements in understanding the underlying mechanisms. Moreover, we discuss potential therapeutic strategies for targeting senescent cells in both the aging process and CKD.

Tuber transcriptome analysis reveals a novel WRKY transcription factor StWRKY70 potentially involved in potato pigmentation.

Tuber flesh pigmentation, conferred by the presence of secondary metabolite anthocyanins, is one of many key agronomic traits for potato tubers. Although several genes of potato anthocyanin biosynthesis have been reported, transcription factors (TFs) contributing to tuber flesh pigmentation are still not fully understood. In this study, transcriptomic profiling of diploid potato accessions with or without tuber flesh pigmentation was conducted and genes of the anthocyanin biosynthesis pathway were found significantly enriched within the 1435 differentially expressed genes (DEGs). Weighted Gene Co-expression Network Analysis (WGCNA) and connectivity analysis pinpointed a subset of 173 genes closely related to the key biosynthetic gene StDFR. Of the eight transcription factors in the subset, group III WRKY StWRKY70, was chosen for showing high connectivity to StDFR and ten other anthocyanin biosynthetic genes and homology to known WRKYs of anthocyanin pathway. The transient activation assay showed StWRKY70 predominantly stimulated the expression of StDFR and StANS as well as the accumulation of anthocyanins by enhancing the function of the MYB transcription factor StAN1. Furthermore, the interaction between StWRKY70 and StAN1 was verified by Y2H and BiFC. Our analysis discovered a new transcriptional activator StWRKY70 which potentially involved in tuber flesh pigmentation, thus may lay the foundation for deciphering how the WRKY-MYB-bHLH-WD40 (WRKY-MBW) complex regulate the accumulation of anthocyanins and provide new strategies to breed for more nutritious potato varieties with enhanced tuber flesh anthocyanins.

Presurgical structural imaging and clinical outcome in combined bed nucleus of the stria terminalis-nucleus accumbens deep brain stimulation for treatment-resistant depression.

Background: Structural imaging holds great potential for precise targeting and stimulation for deep brain stimulation (DBS). The anatomical information it provides may serve as potential biomarkers for predicting the efficacy of DBS in treatment-resistant depression (TRD). Aims: The primary aim is to identify preoperative imaging biomarkers that correlate with the efficacy of DBS in patients with TRD. Methods: Preoperative imaging parameters were estimated and correlated with the 6-month clinical outcome of patients with TRD receiving combined bed nucleus of the stria terminalis (BNST)-nucleus accumbens (NAc) DBS. White matter (WM) properties were extracted and compared between the response/non-response and remission/non-remission groups. Structural connectome was constructed and analysed using graph theory. Distances of the volume of activated tissue (VAT) to the main modulating tracts were also estimated to evaluate the correlations. Results: Differences in fibre bundle properties of tracts, including superior thalamic radiation and reticulospinal tract, were observed between the remission and non-remission groups. Distance of the centre of the VAT to tracts connecting the ventral tegmental area and the anterior limb of internal capsule on the left side varied between the remission and non-remission groups (p=0.010, t=3.07). The normalised clustering coefficient (γ) and the small-world property (σ) in graph analysis correlated with the symptom improvement after the correction of age. Conclusions: Presurgical structural alterations in WM tracts connecting the frontal area with subcortical regions, as well as the distance of the VAT to the modulating tracts, may influence the clinical outcome of BNST-NAc DBS. These findings provide potential imaging biomarkers for the DBS treatment for patients with TRD.

A genomic instability-associated lncRNA signature for predicting prognosis and biomarkers in lung adenocarcinoma.

Genomic instability (GI) was associated with tumorigenesis. However, GI-related lncRNA signature (GILncSig) in lung adenocarcinoma (LUAD) is still unknown. In this study, the lncRNA expression data, somatic mutation information and clinical survival information of LUAD were downloaded from The Cancer Genome Atlas (TCGA) and performed differential analysis. Functional and prognosis analysis revealed that multiple GI-related pathways were enriched. By using univariate and multivariate Cox regression analysis, 5 GI-associated lncRNAs (AC012085.2, FAM83A-AS1, MIR223HG, MIR193BHG, LINC01116) were identified and used to construct a GILncSig model. Mutation burden analysis indicated that the high-risk GI group had much higher somatic mutation count and the risk score constructed by the 5 GI-associated lncRNAs was an independent predictor for overall survival (OS) (P < 0.05). Overall, our study provides valuable insights into the involvement of GI-associated lncRNAs in LUAD and highlights their potential as therapeutic targets.

pH/glutathione-responsive theranostic nanoprobes for chemoimmunotherapy and magnetic resonance imaging of ovarian cancer cells.

The integration of immunotherapy and standard chemotherapy holds great promise for enhanced anticancer effects. In this study, we prepared a pH- and glutathione (GSH)-sensitive manganese-doped mesoporous silicon (MMSNs) based drug delivery system by integrating paclitaxel (PTX) and anti-programmed cell death-ligand 1 antibody (aPD-L1), and encapsulating with polydopamine (PDA) for chemoimmunosynergic treatment of ovarian cancer cells. The nanosystem was degraded in response to the tumor weakly acidic and reductive microenvironment. The Mn2+ produced by degradation can be used as a contrast agent for magnetic resonance (MR) imaging to provide visual exposure to tumor tissue. The released PTX can not only kill tumor cells directly, but also induce immunogenic death (ICD) of tumor cells, which can play a synergistic therapeutic effect with aPD-L1. Therefore, our study is expected to provide a promising strategy for improving the efficacy of cancer immunotherapy and the detection rate of cancer.

Engineered Cyanobacteria-Based Living Materials for Bioremediation of Heavy Metals Both In Vitro and In Vivo.

The pollution caused by heavy metals (HMs) represents a global concern due to their serious environmental threat. Photosynthetic cyanobacteria have a natural niche and the ability to remediate HMs such as cadmium. However, their practical application is hindered by a low tolerance to HMs and issues related to recycling. In response to these challenges, this study focuses on the development and evaluation of engineered cyanobacteria-based living materials for HMs bioremediation. Genes encoding phytochelatins (PCSs) and metallothioneins (MTs) were introduced into the model cyanobacterium Synechocystis sp. PCC 6803, creating PM/6803. The strain exhibited improved tolerance to multiple HMs and effectively removed a combination of Cd2+, Zn2+, and Cu2+. Using Cd2+ as a representative, PM/6803 achieved a bioremediation rate of approximately 21 µg of Cd2+/OD750 under the given test conditions. To facilitate its controllable application, PM/6803 was encapsulated using sodium alginate-based hydrogels (PM/6803@SA) to create "living materials" with different shapes. This system was feasible, biocompatible, and effective for removing Cd2+ under simulated conditions of zebrafish and mice models. Briefly, in vitro application of PM/6803@SA efficiently rescued zebrafish from polluted water containing Cd2+, while in vivo use of PM/6803@SA significantly decreased the Cd2+ content in mice bodies and restored their active behavior. The study offers feasible strategies for HMs bioremediation using the interesting biomaterials of engineered cyanobacteria both in vitro and in vivo.

Effectiveness of Spironolactone in Reducing Osteoporosis and Future Fracture Risk in Middle-Aged and Elderly Hypertensive Patients.

Objective: While the role of aldosterone in bone metabolism is well established, the specific effects of the widely used aldosterone antagonist, spironolactone, on bone health are not fully understood. This study aimed to investigate the effects of spironolactone on osteoporosis and future fracture risk in middle-aged and elderly hypertensive patients, revealing its potential benefits for bone health. Methods: Propensity score matching was employed in this study to create matched groups of spironolactone users and non-users at a 1:4 ratio. We investigated the association between spironolactone use and the risk of osteoporosis using multivariate logistic regression analysis. Furthermore, we conducted multivariate linear regression analysis to explore the relationship between cumulative dosage and the FRAX score. Subgroup analysis was also performed to assess the effects under different stratification conditions. Results: In both pre-match and post-match analyses, multivariable logistic regression revealed a significant reduction in the risk of osteoporosis in the spironolactone usage group (pre-match: odds ratios [OR] 0.406, 95% confidence interval [CI], 0.280-0.588; post-match: OR 0.385, 95% CI, 0.259-0.571). Furthermore, post-match multivariable linear regression demonstrated a clear negative correlation between cumulative spironolactone dosage and the FRAX score. Subgroup analyses consistently supported these findings. Conclusion: This study offers evidence supporting the significant positive impact of the antihypertensive drug spironolactone on bone health, resulting in a substantial reduction in the risk of osteoporosis and future fractures in hypertensive patients. Future research should consider conducting large-scale, multicenter, randomized controlled trials to further investigate the long-term effects of spironolactone on bone health in hypertensive patients.

Altered dynamic functional connectivity of motor cerebellum with sensorimotor network and default mode network in juvenile myoclonic epilepsy.

Objective: To investigate whether changes occur in the dynamic functional connectivity (dFC) of motor cerebellum with cerebral cortex in juvenile myoclonic epilepsy (JME). Methods: We adopted resting-state electroencephalography-functional magnetic resonance imaging (EEG-fMRI) and a sliding-window approach to explore the dFC of motor cerebellum with cortex in 36 JME patients compared with 30 and age-matched health controls (HCs). The motor cerebellum was divided into five lobules (I-V, VI, VIIb, VIIIa, and VIIIb). Additionally, correlation analyses were conducted between the variability of dFC and clinical variables in the Juvenile Myoclonic Epilepsy (JME) group, such as disease duration, age at disease onset, and frequency score of myoclonic seizures. Results: Compared to HCs, the JME group presented increased dFC between the motor cerebellum with SMN and DMN. Specifically, connectivity between lobule VIIb and left precentral gyrus and right inferior parietal lobule (IPL); between lobule VIIIa and right inferior frontal gyrus (IFG) and left IPL; and between lobule VIIIb and left middle frontal gyrus (MFG), bilateral superior parietal gyrus (SPG), and left precuneus. In addition, within the JME group, the strength of dFC between lobule VIIIb and left precuneus was negatively (r = -0.424, p = 0.025, Bonferroni correction) related with the frequency score of myoclonic seizures. Conclusion: In patients with JME, there is a functional dysregulation between the motor cerebellum with DMN and SMN, and the variability of dynamic functional connectivity may be closely associated with the occurrence of motor symptoms in JME.