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1.
Phys Med Biol ; 2024 Oct 03.
Article in English | MEDLINE | ID: mdl-39362274

ABSTRACT

OBJECTIVE: T2-weighted 2D fast spin echo sequence serves as the standard sequence in clinical pelvic MR imaging protocols. However, motion artifacts and blurring caused by peristalsis present significant challenges. Patient preparation such as administering antiperistaltic agents is often required before examination to reduce artifacts, which discomfort the patients. This work introduce a novel dynamic approach for T2 weighted pelvic imaging to address peristalsis-induced motion issue without any patient preparation. Approach: A rapid dynamic data acquisition strategy with complementary sampling trajectory is designed to enable highly undersampled motion-resistant data sampling, and an unrolling method based on deep equilibrium model is leveraged to reconstruct images from the dynamic sampled k-space data. Moreover, the fix-point convergence of the equilibrium model ensures the stability of the reconstruction. The high acceleration factor in each temporal phase, which is much higher than that in traditional static imaging, has the potential to effectively freeze pelvic motion, thereby transforming the imaging problem from conventional motion prevention or removal to motion reconstruction. Main results: Experiments on both retrospective and prospective data have demonstrated the superior performance of the proposed dynamic approach in reducing motion artifacts and accurately depicting structural details compared to standard static imaging. Significance: The proposed dynamic approach effectively captures motion states through dynamic data acquisition and deep learning-based reconstruction, addressing motion-related challenges in pelvic imaging.

3.
Ecotoxicol Environ Saf ; 285: 117116, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-39357377

ABSTRACT

Ambient air pollution is a significant environmental risk factor for adverse pregnancy outcomes, including preterm birth. However, the impact of different pollutants across various regions and trimesters of pregnancy has not been fully investigated in Brazil. This study aimed to examine the associations between exposure to PM2.5, NO2, and O3 during different trimesters of pregnancy and the risk of preterm birth across five regions of Brazil. We used logistic regression models to estimate the odds ratios (OR) of preterm birth associated with PM2.5, NO2, and O3 adjusting for potential confounders such as maternal age, education, and socioeconomic status. Our study included over 9.9 million live births from 2001 to 2018, with data obtained from the Ministry of Health in Brazil. On average, for each 1-µg/m3 increase in PM2.5, we estimated a 0.26 % (95 % CI: 0.08-0.44 %) increase in the risk of preterm birth nationally in the first trimester. For NO2, each 1ppb increase was associated with a percentage increase in preterm birth risk of 7.26 % (95 % CI: 4.77-9.74 %) in the first trimester, 8.05 % (95 % CI: 5.73-10.38 %) in the second trimester, and 7.48 % (95 % CI: 5.25-9.72 %) in the third trimester. For O3, each 1ppb increase was associated with a percentage increase in preterm birth risk of 1.24 % (95 % CI: 0.29-2.18 %) in the first trimester, 1.51 % (95 % CI: 0.60-2.41 %) in the second trimester, and 0.72 % (95 % CI: -0.18-1.62 %) in the third trimester. This study highlights the significant impact of ambient air pollution on preterm birth risk in Brazil, with significant regional variations. Our findings underscore the need for targeted public health interventions to mitigate the effects of air pollution on pregnancy outcomes, particularly in the most affected regions.

4.
Article in English | MEDLINE | ID: mdl-39360599

ABSTRACT

Adrenal vein sampling (AVS) is the current recommended procedure for identifying unilateral subtypes of primary aldosteronism (PA), which are amenable to surgery with the potential for cure. AVS is a technically challenging procedure usually undertaken by interventional radiologists at tertiary centres. However, there are numerous variations in AVS protocols relating to patient preparation, sampling techniques and interpretation which may impact the success of AVS and patient care. To reduce practice variations, improve the success rates of AVS and optimise patient outcomes, we established an Australian and New Zealand AVS Working Group and developed evidence-based expert consensus recommendations for the preparation, performance and interpretation of AVS. These recommendations can be used by all healthcare professionals in a multidisciplinary team who look after the diagnosis and management of PA.

5.
Circulation ; 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-39351674

ABSTRACT

BACKGROUND: Primary aldosteronism, characterized by renin-independent aldosterone production, is associated with adverse cardiovascular remodeling and outcomes. Elevated cardiovascular risk is observed even in subclinical forms of primary aldosteronism according to studies conducted primarily in middle-aged and elderly populations. This study aimed to assess whether early changes in primary aldosteronism biomarkers during young adulthood are associated with arterial stiffness and left ventricular mass index (LVMI) before the onset of overt disease. METHODS: The Raine Study is a longitudinal, population-based cohort study in Western Australia that enrolled women during pregnancy. We analyzed the data from the offspring of these women at 17 (2006-2009) and 27 (2016-2018) years of age. Participants with elevated high-sensitivity C-reactive protein (>10 mg/L) and female participants who were on oral contraception were excluded. Pulse wave velocity and aortic augmentation index were measured by SphygmoCor Pulse Wave System at both ages, and aortic distensibility and LVMI were measured by cardiac magnetic resonance imaging at 27 years. Multivariable linear regression was used to examine the relationship between plasma renin, aldosterone, or aldosterone-to-renin ratio and arterial stiffness and LVMI. Mediation analysis was used to test the role of systolic blood pressure. RESULTS: This study included 859 participants at 17 (38.0% female) and 758 participants at 27 (33.2% female) years of age. Females had lower renin concentration at both 17 (20.7 mU/L versus 25.7 mU/L; P<0.001) and 27 (12.0 mU/L versus 15.4 mU/L; P<0.001) years of age; hence, the aldosterone-to-renin ratio was significantly higher at both 17 (18.2 versus 13.5; P<0.001) and 27 (21.0 versus 15.6; P<0.001) years of age in females compared with males. At 27 years of age, a significant association was detected between aldosterone and LVMI in males (ß=0.009 [95% CI, 0.001-0.017]; P=0.027) and between aldosterone-to-renin ratio and LVMI in females (ß=0.098 [95% CI, 0.001-0.196]; P=0.050) independently of systolic blood pressure and other confounders. No association was found between primary aldosteronism biomarkers and measures of arterial stiffness (pulse wave velocity, aortic augmentation index, and aortic distensibility) at either age. CONCLUSIONS: Aldosterone concentration and aldosterone-to-renin ratio were positively associated with the LVMI in young males and females, respectively, independently of systolic blood pressure. Long-term follow-up is required to determine whether the relationship persists over time, and clinical trials are needed to assess the cardiovascular benefits of early interventions to block aldosterone.

6.
Front Cell Neurosci ; 18: 1440409, 2024.
Article in English | MEDLINE | ID: mdl-39360264

ABSTRACT

Background: Gliomas, originating from the most common non-neuronal cells in the brain (glial cells), are the most common brain tumors and are associated with high mortality and poor prognosis. Glioma cells exhibit a tendency to disrupt normal cell-cycle regulation, leading to abnormal proliferation and malignant growth. This study investigated the predictive potential of GJC1 in gliomas and explored its relationship with the cell cycle. Methods: Retrospective analysis of RNA-seq and single-cell sequencing data was conducted using the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) databases. The differential expression of GJC1 in gliomas with various pathological features and in different non-neuronal cell groups was analyzed. Functional data were examined using gene set variation analysis (GSVA). Furthermore, CellMiner was used to evaluate the relationship between GJC1 expression and predicted treatment response across these databases. Results: GJC1 expression was enriched in high-grade gliomas and 1p/19q non-codeletion gliomas. GJC1 enrichment was observed in classical and mesenchymal subtypes within the TCGA glioma subtype group. In single-cell subgroup analysis, GJC1 expression was higher in glioma tissues compared to other non-neuronal cells. Additionally, the TCGA classical subtype of glioma cells exhibited more GJC1 expression than the other subgroups. GJC1 emerged as an independent prognostic factor for overall survival in glioma. GSVA unveiled potential mechanisms by which GJC1 may impact cell-cycle regulation in glioma. Finally, a significant correlation was observed between GJC1 expression and the sensitivity of multiple anti-cancer drugs. Conclusion: These findings confirmed GJC1 as a novel biomarker and provided insights into the differential gene expression in non-neuronal cells and the impact of the cell cycle on gliomas. Consequently, GJC1 may be used to predict glioma prognosis and has potential therapeutic value.

7.
Int Immunopharmacol ; 143(Pt 1): 113280, 2024 Sep 30.
Article in English | MEDLINE | ID: mdl-39353395

ABSTRACT

There is growing evidence that the protein family of Gasdermins (GSDMs) play an essential role during the progression of colorectal cancer (CRC). However, it is not completely clear that how GSDMB, abundantly expressed in epithelial cells of gastrointestinal tract, regulates the tumorigenesis of CRC. A wealth of evidence linking GSDMB to the pathogenesis of cancer has come from genome-wide association studies. Here, we provide evidence that aberrantly upregulated GSDMB is responsible for suppressing the CRC progression by using in vitro cell and intestinal organoid, as well as in vivo GSDMB transgenic mice models. Mechanistically, GSDMB interacts with insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), which directly binds to and recognizes the 3'-UTR of dual specificity phosphatase 6 (DUSP6) mRNA, enhances the translation of DUSP6 protein and inhibits downstream ERK phosphorylation, thereby facilitating cell death and restraining cell proliferation. Our results suggest that GSDMB has potential as a novel therapeutic target for CRC treatment.

8.
Cell Stem Cell ; 2024 Sep 27.
Article in English | MEDLINE | ID: mdl-39353427

ABSTRACT

Directed differentiation of stem cells toward chondrogenesis in vitro and in situ to regenerate cartilage suffers from off-target differentiation and hypertrophic tendency. Here, we generated a cartilaginous organoid system from human expanded pluripotent stem cells (hEPSCs) carrying a COL2A1mCherry and COL10A1eGFP double reporter, enabling real-time monitoring of chondrogenesis and hypertrophy. After screening 2,040 FDA-approved drugs, we found that α-adrenergic receptor (α-AR) antagonists, especially phentolamine, stimulated chondrogenesis but repressed hypertrophy, while α2-AR agonists reduced chondrogenesis and induced hypertrophy. Phentolamine prevented cartilage degeneration in hEPSC cartilaginous organoid and human cartilage explant models and stimulated microfracture-activated endogenous skeletal stem cells toward hyaline-like cartilage regeneration without fibrotic degeneration in situ. Mechanistically, α2-AR signaling induced hypertrophic degeneration via cyclic guanosine monophosphate (cGMP)-dependent secretory leukocyte protease inhibitor (SLPI) production. SLPI-deleted cartilaginous organoid was degeneration resistant, facilitating large cartilage defect healing. Ultimately, targeting α2-AR/SLPI was a promising and clinically feasible strategy to regenerate cartilage via promoting chondrogenesis and repressing hypertrophy.

9.
Clin Transl Sci ; 17(9): e70033, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39300734

ABSTRACT

Chronic pain represents a significant unmet medical need, affecting one-fifth of the U.S. population. EC5026 is a small molecule inhibitor of the enzyme soluble epoxide hydrolase (sEH) which is being developed as a novel non-opioid, non-NSAID analgesic. EC5026 prolongs the action of epoxy fatty acids, endogenous analgesic lipid mediators that are rapidly metabolized by sEH. We evaluated the safety and pharmacokinetic profile of EC5026 in two phase I trials, a single-ascending dose (SAD) study and a fed-fasted study. The SAD study evaluated EC5026 doses ranging from 0.5 to 24 mg in healthy volunteers. EC5026 was well tolerated. No treatment-emergent adverse events were considered related to EC5026. No apparent treatment- or dose-related trends in laboratory results, vital signs, physical examinations, or electrocardiograms were observed. A linear, near-dose-proportional increase in exposure was observed with progressive doses in the SAD study; plasma exposure was below or near the lower limit of quantification after 0.5-2 mg doses. Mean half-lives ranged from 41.8 to 59.1 h. for doses of 8-24 mg, supporting a once-daily dosing regimen. In the fed-fasted study using 8 mg EC5026 tablets, higher peak concentrations (66%) and total exposures (53%) were observed under the fed condition. Plasma concentrations declined in a monoexponential manner with mean half-lives of 59.5 h. in the fed state and 66.9 h. in the fasted state. Future clinical trials using EC5026 for the treatment of pain are justified based on the favorable outcomes from both clinical trials along with preclinical evidence of analgesic activity.


Subject(s)
Food-Drug Interactions , Healthy Volunteers , Humans , Adult , Male , Double-Blind Method , Female , Young Adult , Middle Aged , Dose-Response Relationship, Drug , Epoxide Hydrolases/antagonists & inhibitors , Fasting/blood , Adolescent , Administration, Oral , Half-Life
10.
Rev Med Virol ; 34(5): e2584, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39304923

ABSTRACT

Neurotropic viruses have been implicated in altering the central nervous system microenvironment and promoting brain metastasis of breast cancer through complex interactions involving viral entry mechanisms, modulation of the blood-brain barrier, immune evasion, and alteration of the tumour microenvironment. This narrative review explores the molecular mechanisms by which neurotropic viruses such as Herpes Simplex Virus, Human Immunodeficiency Virus, Japanese Encephalitis Virus, and Rabies Virus facilitate brain metastasis, focusing on their ability to disrupt blood-brain barrier integrity, modulate immune responses, and create a permissive environment for metastatic cell survival and growth within the central nervous system. Current therapeutic implications and challenges in targeting neurotropic viruses to prevent or treat brain metastasis are discussed, highlighting the need for innovative strategies and multidisciplinary approaches in virology, oncology, and immunology.


Subject(s)
Brain Neoplasms , Breast Neoplasms , Humans , Breast Neoplasms/pathology , Breast Neoplasms/virology , Breast Neoplasms/therapy , Brain Neoplasms/secondary , Brain Neoplasms/virology , Brain Neoplasms/therapy , Female , Blood-Brain Barrier/virology , Animals , Tumor Microenvironment , Rabies virus/physiology , Rabies virus/pathogenicity , Rabies virus/immunology , Simplexvirus/physiology
11.
Angew Chem Int Ed Engl ; : e202414340, 2024 Sep 21.
Article in English | MEDLINE | ID: mdl-39305151

ABSTRACT

The bisbenzylisoquinoline alkaloids (bisBIAs) have attracted tremendous attention from the synthetic community due to their diverse and intriguing biological activities. Herein, we report the convergent and modular chemoenzymatic syntheses of eight bisBIAs bearing various substitutes and linkages in 5-7 steps. The gram-scale synthesis of various well-designed enantiopure benzylisoquinoline monomers was accomplished via an enzymatic stereoselective Pictet-Spengler reaction, followed by regioselective enzymatic methylation or chemical functionalizations in a sequential one-pot process. A modified intermolecular copper-mediated Ullmann coupling enabled the concise and efficient total synthesis of five different linear bisBIAs with either head-to-tail or tail-to-tail linkage.  A biomimetic oxidative phenol dimerization selectively formed the sterically hindered, electron-rich diaryl ether bond, and subsequent intramolecular Suzuki-Miyaura domino reaction or Ullmann coupling facilitated the first enantioselective total synthesis of three macrocyclic bisBIAs, including ent-isogranjine, tetrandrine and O-methylrepandine. This study highlights the great potential of chemoenzymatic strategies in the total synthesis of diverse bisBIAs and paves the way to further explore the biological functions of these natural products.

12.
Water Res ; 267: 122469, 2024 Sep 17.
Article in English | MEDLINE | ID: mdl-39305526

ABSTRACT

Flooding, carrying sediments, inundates farmlands across the world due to extreme adverse weather conditions. The casualties and property damage associated with flooding are important direct impacts. However, there is currently insufficient understanding of the remobilization and distribution of heavy metals (HMs) caused by flooding. Few studies have specifically considered flooding as a pathway for HMs contamination of soil. Herein, a novel methodological framework for revealing the input pathways of HMs in agricultural soils in mining-intensive areas is proposed and applied. Flooding is considered one of the pathways for HMs inputs during source apportionment. The results demonstrated a high degree of overlap between the distribution characteristics of major HMs in agricultural soils and sediments. The degree of soil Cd pollution was significantly positively correlated with the inundation depth in the flooded area. It took 8.4-11.5 times of flood inundation or 98.5-119.9 years of accumulation of atmospheric deposition to reach HMs contamination levels in the soil of the study area. Flooding brought in most of the soil Cd, while atmospheric deposition was the primary input pathway for soil Pb and Zn. Our results identified the role of flood inundation on the input of HMs in mining-intensive areas. These results demonstrated the value of our framework for studying the impact of flooding on HMs in agricultural soils from the perspective of input pathways, providing new insights not only into identifying the sources of soil HMs but also into enhancing understanding of the impact of flooding on soil environments. With the potential increase in the frequency and intensity of flooding inundating farmlands in the future, it is essential to consider flooding as a pathway for HMs inputs in order to comprehensively assess their environmental impact.

13.
Environ Int ; 192: 109019, 2024 Sep 18.
Article in English | MEDLINE | ID: mdl-39305790

ABSTRACT

Both ambient fine particulate matter (PM2.5) and aging are important urban concerns. However, the associations between PM2.5 constituents and the acceleration of aging (AA) remain unclear. We included 16,051 adults (aged 25-80 years) with 19,252 medical observations in Taiwan during 2008-2017. 2-year average PM2.5 and its five major constituents were assessed using a two-stage machine learning model at a resolution of 1 km2. AA was determined by the difference between the Klemera-Doubal biological age and chronological age. A linear mixed model (LMM) with inverse probability weights was used to examine the associations between AA and air pollution. In a semi-randomized study design, we applied a post-matching LMM to assess the impacts of changes in air pollution exposure on AA. Each interquartile range increase in ambient PM2.5, SO4-2, NO3-, NH4+, organic matters (OM), and black carbon (BC) was associated with a 0.20 (95 %confidence interval [CI]: 0.17-0.24), 0.19 (0.15-0.23), 0.14 (0.11-0.18), 0.21 (0.17-0.24), 0.22 (0.19-0.26) and 0.25 (0.21-0.28) year increase in AA, respectively. BC was generally associated with the greatest increase in AA as compared to other constituents. We did not find evident thresholds in their concentration-response associations. Participants exposed to increased levels of PM2.5, SO4-2, NO3-, NH4+, OM, and BC experienced an increase in AA of 0.11 (-0.07-0.29), 0.20 (0.02-0.39), 0.15 (-0.02-0.33), 0.12 (-0.07-0.31), 0.24 (0.07-0.41), and 0.30 (0.07-0.52) years, respectively, compared to those exposed to decreased/unchanged levels. Long-term exposure to ambient PM2.5 and its constituents may accelerate biological aging among Chinese adults. Exposed to increased levels may further aggregate the aging process. This study suggests that reducing exposure to air pollution is beneficial, even for residents within moderately-to-highly polluted regions, such as Taiwan. Rigorous regulation of PM2.5 and its constituents may prevent the acceleration of biological age.

14.
Expert Opin Drug Saf ; : 1-8, 2024 Sep 20.
Article in English | MEDLINE | ID: mdl-39301684

ABSTRACT

BACKGROUND: The association between pioglitazone (PLZ) and bladder cancer (BC) remains controversial in several randomized control trials, meta-analyses of multiple prospective studies, and large-scale observational studies. RESEARCH DESIGN AND METHODS: Adverse event (AE) data from 1 January 2004 to 31 March 2024 were extracted from the Food and Drug Administration Adverse Event Reporting System (FAERS) database. Disproportionality analysis were applied to quantify the signals of PLZ related BC. RESULTS: In total, 17,627,524 AE reports were recorded in the FAERS database, of which 1366 were PLZ-related BCs. More male than female patients were reported. The median age of patients was 70 years old. The peak in the annual report occurred in 2011. A total of 602 AEs reported time to onset (TTO) and the median TTO was 1023 days. In this study, BC and BC recurrence were strong signal, whereas BC stage 0 (with cancer in situ), stage ii and iii were weak signals. CONCLUSIONS: This study comprehensively demostrated the PLZ-induced risk of BC in patients with diabetes mellitus using the FAERS database. The results demonstrated that the patients treated with PLZ were more likely to develop BC. The male and aging attributed more cases to BC-related reports of PLZ treated patients.

15.
Biosensors (Basel) ; 14(9)2024 Aug 23.
Article in English | MEDLINE | ID: mdl-39329783

ABSTRACT

Due to the extremely low Reynolds number, the mixing of substances in laminar flow within microfluidic channels primarily relies on slow intermolecular diffusion, whereas various rapid reaction and detection requirements in lab-on-a-chip applications often necessitate the efficient mixing of fluids within short distances. This paper presents a magnetic pillar-shaped particle fabrication device capable of producing particles with planar shapes, which are then utilized to achieve the rapid mixing of multiple fluids within microchannels. During the particle fabrication process, a degassed PDMS chip provides self-priming capabilities, drawing in a UV-curable adhesive-containing magnetic powder and distributing it into distinct microwell structures. Subsequently, an external magnetic field is applied, and the chip is exposed to UV light, enabling the mass production of particles with specific magnetic properties through photo-curing. Without the need for external pumping, this chip-based device can fabricate hundreds of magnetic particles in less than 10 min. In contrast to most particle fabrication methods, the degassed PDMS approach enables self-priming and precise dispensing, allowing for precise control over particle shape and size. The fabricated dual-layer magnetic particles, featuring fan-shaped blades and disk-like structures, are placed within micromixing channels. By manipulating the magnetic field, the particles are driven into motion, altering the flow patterns to achieve fluid mixing. Under conditions where the Reynolds number in the chip ranges from 0.1 to 0.9, the mixing index for substances in aqueous solutions exceeds 0.9. In addition, experimental analyses of mixing efficiency for fluids with different viscosities, including 25 wt% and 50 wt% glycerol, reveal mixing indices exceeding 0.85, demonstrating the broad applicability of micromixers based on the rapid rotation of magnetic particles.


Subject(s)
Lab-On-A-Chip Devices , Microfluidic Analytical Techniques , Microfluidics , Dimethylpolysiloxanes/chemistry , Magnetics
16.
Entropy (Basel) ; 26(9)2024 Sep 04.
Article in English | MEDLINE | ID: mdl-39330091

ABSTRACT

This paper explores physical layer group key generation in wireless relay networks with a star topology. In this setup, the relay node plays the role of either a trusted or untrusted central node, while one legitimate node (Alice) acts as the reference node. The channel between the relay and Alice serves as the reference channel. To enhance security during the channel measurement stage, a cooperative jamming-based scheme is proposed in this paper. This scheme allows the relay to obtain superimposed channel observations from both the reference channel and other relay channels. Then, a public discussion is utilized to enable all nodes to obtain estimates of the reference channel. Subsequently, the legitimate nodes can agree on a secret key (SK) that remains secret from the eavesdropper (Eve), or a private key (PK) that needs to be secret from both the relay and Eve. This paper also derives the lower and upper bounds of the SK/PK capacity. Notably, it demonstrates that there exists only a small constant difference between the SK/PK upper and lower bounds in the high signal-to-noise ratio (SNR) regime. Simulation results confirm the effectiveness of the proposed scheme for ensuring security and efficiency of group key generation.

17.
Metabolites ; 14(9)2024 Sep 10.
Article in English | MEDLINE | ID: mdl-39330499

ABSTRACT

To explore the effects of altered amino acids (AAs) and the carnitine metabolism in non-pregnant women with infertility (NPWI), pregnant women without infertility (PWI) and infertility-treated pregnant women (ITPW) compared with non-pregnant women (NPW, control), and develop more efficient models for the diagnosis of infertility and pregnancy, 496 samples were evaluated for levels of 21 AAs and 55 carnitines using targeted high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS). Three methods were used to screen the biomarkers for modeling, with eight algorithms used to build and validate the model. The ROC, sensitivity, specificity, and accuracy of the infertility diagnosis training model were higher than 0.956, 82.89, 66.64, and 82.57%, respectively, whereas those of the validated model were higher than 0.896, 77.67, 69.72, and 83.38%, respectively. The ROC, sensitivity, specificity, and accuracy of the pregnancy diagnosis training model were >0.994, 96.23, 97.79, and 97.69%, respectively, whereas those of the validated model were >0.572, 96.39, 93.03, and 94.71%, respectively. Our findings indicate that pregnancy may alter the AA and carnitine metabolism in women with infertility to match the internal environment of PWI. The developed model demonstrated good performance and high sensitivity for facilitating infertility and pregnancy diagnosis.

18.
Endocr Connect ; 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-39331788

ABSTRACT

The elevated level of hepatic oxidative stress (OS) in polycystic ovary syndrome (PCOS) is one of the important causes of liver abnormalities. Therefore, decreasing the level of hepatic OS in PCOS is beneficial to reduce the risk of PCOS-related liver diseases. Melatonin (MT), recognized as a potent antioxidant. Nevertheless, the efficacy of MT in alleviating hepatic OS associated with PCOS is yet to be established, and the precise mechanisms through which MT exerts its antioxidant effects remain to be fully elucidated. The aim of this study was to explore the potential mechanism by which MT reduces hepatic OS in PCOS. First, we detected elevated OS levels in the PCOS samples. Subsequently, with MT pretreatment, we discovered that MT could significantly diminish the levels of OS, liver triglyceride (TG), total cholesterol (TC), alanine aminotransferase (ALT) and aspartate aminotransferase (AST),while concurrently ameliorating mitochondrial structural damage in PCOS liver. Furthermore, we identified elevated autophagy levels in the liver of PCOS rats and an inhibition of the Keap1-Nrf2 pathway. Through MT pretreatment, the expression of LC3 was significantly decreased, while the Keap1-Nrf2 pathway was activated. Our study showed that MT could affect the Nrf2 pathway dependent on the P62/LC3 autophagy pathway, thereby attenuating hepatic OS in PCOS. These findings offer novel insights and research avenues for the study of PCOS-related liver diseases.

19.
J Clin Neurosci ; 129: 110853, 2024 Sep 29.
Article in English | MEDLINE | ID: mdl-39348790

ABSTRACT

Spinal disorders pose a significant global health challenge, affecting nearly 5% of the population and incurring substantial socioeconomic costs. Over time, spinal neurosurgery has evolved from basic 19th-century techniques to today's minimally invasive procedures. The recent integration of technologies such as robotic assistance and advanced imaging has not only improved precision but also reshaped treatment paradigms. This review explores key innovations in imaging, biomaterials, and emerging fields such as AI, examining how they address long-standing challenges in spinal care, including enhancing surgical accuracy and promoting tissue regeneration. Are we at the threshold of a new era in healthcare technology, or are these innovations merely enhancements that may not fundamentally advance clinical care? We aim to answer this question by offering a concise introduction to each technology and discussing in depth its status and challenges, providing readers with a clearer understanding of its actual potential to revolutionize surgical practices.

20.
Sci Total Environ ; 953: 176058, 2024 Nov 25.
Article in English | MEDLINE | ID: mdl-39241884

ABSTRACT

Mechanisms underlying the effects of ecological disturbance on aquatic ecosystems remain uncertain in subtropical regions. Here, we used a proxy-based approach to explore the community dynamics of testate amoebae (Arcellinida and Euglyphida) in two subtropical deep reservoirs (Tingxi and Shidou) in Xiamen, southeastern China, over a three-year period. Specifically, we employed drought and typhoon events recorded by weather station as proxies for ecological disturbance and chlorophyll-a estimated through fluorometry as a proxy for testate amoeba food. We addressed three questions: (1) Does typhoon-induced ecological disturbance affect the distribution patterns of testate amoebae in subtropical reservoirs? (2) Do typhoon- and drought-induced ecological disturbances affect the testate amoeba community across different water layers of subtropical reservoirs similarly? (3) Do stochastic or deterministic processes shaping the testate amoeba community over time exhibit similar patterns in different water layers of subtropical reservoirs? The typhoon-induced ecological disturbance resulted in pronounced shifts in the distribution patterns of testate amoebae, characterized by lower shell influx in surface waters (11-12 ind. mL-1 d-1) and higher shell influx in middle and bottom waters (12-22 ind. mL-1 d-1). The impact of typhoon-and drought-induced ecological disturbance was more pronounced in surface waters, and its pure explanation accounted for 29.5-35.5 % community variation in a variation partitioning analysis. The effect of stochastic processes revealed by the neutral model increased with water depths, accounting for 63.3-76.5 % of the community variation in the surface, 77.4-82.6 % in the middle, and 82.8-88.1 % in the bottom water. The effect of deterministic processes shown by the null model decreased with water depth and remained relatively low across all water layers. These results suggest contrasting patterns of assembly mechanisms underlying the testate amoeba community responses to ecological disturbance, with the balance perhaps shaped by water depth and the average water residence time in a reservoir.


Subject(s)
Amoeba , China , Environmental Monitoring/methods , Ecosystem , Droughts , Cyclonic Storms
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