Outcomes and Imaging Surveillance Adherence in Juxta-Renal Aortic Aneurysms Repairs: A VASQIP Retrospective Study.

OBJECTIVE: Fenestrated endovascular aortic repair (FEVAR) has demonstrated its value in the management of juxtarenal abdominal aortic aneurysms (JAAA), but data were largely derived from clinical trials and high-volume centers. Although routine imaging surveillance is recommended following endovascular interventions, little is known regarding follow-up compliance post-FEVAR. We examined the real-world treatment outcomes and adherence to the postoperative follow-up protocol after elective interventions for JAAA at Veteran Affairs (VA) health care facilities, the largest integrated health care system in the United State. METHODS: This is a retrospective cohort study. We queried the Veteran Affairs Surgical Quality Improvement Program (VASQIP) database for elective FEVARs and juxtarenal open surgical repairs (j-OSR), then merged follow-up imaging and mortality information. Our primary endpoints were mortality following FEVAR and j-OSR, and adherence to surveillance guidelines. Secondary endpoints included short-term postoperative complications. RESULTS: A total of 1110 veterans who underwent first-time JAAA repair between 2002 and 2019 (FEVAR, 26% [n=290]; j-OSR, 74% [n=820]) were included in the analysis. The number of j-OSR captured in the database gradually declined by 50%, from 62 interventions in 2002 to 28 in 2019, while FEVAR procedures quadrupled from 20 procedures in 2014 to 94 in 2019. The median follow-up was 3.99 years (95% confidence interval [CI]: 3.73-4.87) for FEVAR patients, and 12.80 (12.31-13.70) for those that underwent jOSR. A significantly lower risk of 30-day mortality was observed following FEVAR compared to j-OSR (1% vs 5%, odds ratio [OR]: 5.03 [1.54-16.38]; p=0.003). At 5 years, FEVAR was linked with significantly higher mortality (41.5% vs 21%, p<0.001) after adjusting for confounders (aHR=2.10 [1.56-2.82], p<0.001). Of surviving patients, the follow-up imaging rate was 66.3% by 1-year post-FEVAR. Follow-up rate at 5 years was 7% post-FEVAR compared to 32% post j-OSR. CONCLUSION: Elective FEVAR is associated with lower perioperative mortality and morbidities compared to elective j-OSR for juxtarenal aortic aneurysms. However, the perioperative survival benefits of FEVAR diminish over time, with its mortality surpassing that of j-OSR at longer follow-up periods. The compliance with post-FEVAR imaging surveillance is also low. Further research is warranted to develop strategies to improve adherence to imaging surveillance protocols. CLINICAL IMPACT: This study provides real-world evidence on the outcomes and follow-up adherence following fenestrated endovascular aortic repair (FEVAR) for juxtarenal abdominal aortic aneurysms (JAAA) in the Veterans Affairs health care system. With FEVAR's increasing use, the findings highlight the need for improved surveillance protocols, as adherence to postoperative imaging declines significantly after the first year. Clinicians should be aware of the risk of long-term mortality despite FEVAR's short-term benefits, urging better follow-up strategies that relay a survival benefit for patients.

Circ_001653 alleviates sepsis associated-acute kidney injury by recruiting BUD13 to regulate KEAP1/NRF2/HO-1 signaling pathway.

BACKGROUND: The kidney is exceptionally vulnerable during sepsis, often resulting in sepsis-associated acute kidney injury (SA-AKI), a condition that not only escalates morbidity but also significantly raises sepsis-related mortality rates. Circular RNA circ_001653 has been previously reported to be upregulated in the serum of SA-AKI patients, while the role and underlying mechanism of circ_001653 in SA-AKI remains unknown. In this study, we aimed to explore the functional role and the molecular mechanism of circ_001653 in the pathogenesis of SA-AKI. METHODS: LPS-stimulated HK-2 cells and ligation and perforation of cecum (CLP)-induced rats were used as in vitro and in vivo models of SA-AKI. The target gene expression levels were measured using qRT-PCR and western blot. Renal function (BUN, sCr, uNGAL, and uKIM-1), and renal pathological changes were detected in septic mice. TUNEL and EdU assays were conducted to measure apoptosis and proliferation rates in vitro. DCFH-DA staining was used to detect ROS levels in vitro and in vivo. Oxidative stress markers (SOD, GSH-Px, MDA, and SOD), and inflammation markers (IL-1ß, IL-6, and TNF-α) were determined using commercial kits both in vitro and in vivo. Additionally, gain-and-loss-of-function assays and mechanistic experiments were conducted to explore the regulatory role of circ_001653 in SA-AKI pathogenesis. RESULTS: Data showed that circ_001653 expression was high in LPS-stimulated HK-2 cells and CLP-induced rat renal tissue and was mainly localized in the cytoplasm. Notably, circ_001653 silencing alleviated SA-AKI by reducing apoptosis and alleviating oxidative stress and inflammation in HK-2 cells and renal tissue of rats. Mechanistically, it was found that circ_001653 alleviated SA-AKI by recruiting BUD13 to activate the KEAP1/Nrf2/HO-1 signaling pathway. CONCLUSIONS: To summarize, our study is the first to reveal elevated expression of circ_001653 in sepsis-associated AKI, and its downregulation effectively attenuates AKI by reducing apoptosis, inflammation, and oxidative stress. Mechanistically, circ_001653 exerts its effects by recruiting BUD13 to activate the KEAP1/Nrf2/HO-1 signaling pathway. These findings suggest circ_001653 as a potential therapeutic target for the drug development of sepsis-associated AKI.

The p-MYH9/USP22/HIF-1α axis promotes lenvatinib resistance and cancer stemness in hepatocellular carcinoma.

Lenvatinib is a targeted drug used for first-line treatment of hepatocellular carcinoma (HCC). A deeper insight into the resistance mechanism of HCC against lenvatinib is urgently needed. In this study, we aimed to dissect the underlying mechanism of lenvatinib resistance (LR) and provide effective treatment strategies. We established an HCC model of acquired LR. Cell counting, migration, self-renewal ability, chemoresistance and expression of stemness genes were used to detect the stemness of HCC cells. Molecular and biochemical strategies such as RNA-sequencing, immunoprecipitation, mass spectrometry and ubiquitination assays were used to explore the underlying mechanisms. Patient-derived HCC models and HCC samples from patients were used to demonstrate clinical significance. We identified that increased cancer stemness driven by the hypoxia-inducible factor-1α (HIF-1α) pathway activation is responsible for acquired LR in HCC. Phosphorylated non-muscle myosin heavy chain 9 (MYH9) at Ser1943, p-MYH9 (Ser1943), could recruit ubiquitin-specific protease 22 (USP22) to deubiquitinate and stabilize HIF-1α in lenvatinib-resistant HCC. Clinically, p-MYH9 (Ser1943) expression was upregulated in HCC samples, which predicted poor prognosis and LR. A casein kinase-2 (CK2) inhibitor and a USP22 inhibitor effectively reversed LR in vivo and in vitro. Therefore, the p-MYH9 (Ser1943)/USP22/HIF-1α axis is critical for LR and cancer stemness. For the diagnosis and treatment of LR in HCC, p-MYH9 (Ser1943), USP22, and HIF-1α might be valuable as novel biomarkers and targets.

Effect of ART treatments on maternal and neonatal outcomes in singleton live births: A large-scale retrospective cohort study.

Background: The increased risk of pregnancy complications in the ART population has been reported, but the source of these risks remains controversial. The study aims to evaluate the association between ART treatments and patient characteristics with maternal and neonatal outcomes. Methods: This was a retrospective analysis of 45,159 singleton pregnant women at a hospital between 2018 and 2021. The maternal and neonatal outcomes included pregnancy-induced hypertension (PIH), preeclampsia (PE), gestational diabetes mellitus (GDM), placental abruption (PA), placenta accreta spectrum (PAS), postpartum hemorrhage (PPH), cesarean section, iatrogenic and spontaneous preterm birth, small for gestational age (SGA), low birth weight (LBW), macrosomia, and birth defects. We assessed the outcomes among the fresh embryo transfer (ET), frozen embryo transfer (FET), and spontaneous conception (SC) groups. Potential risk factors were further analyzed in the ART population. Results: FET was associated with higher risks for PIH (SC: AOR, 1.97(1.51-2.57); fresh ET: AOR, 1.68(1.03-2.72)), PE (SC: 2.28(1.86-2.80); fresh ET: AOR, 1.61(1.11-2.33)), PAS (SC: AOR, 3.89(3.39-4.46); fresh ET: AOR, 2.23(1.70-2.92)), PPH (SC: AOR, 3.46(2.76-4.34)); fresh ET: 2.09(1.39-3.14)), and macrosomia (SC: 1.53(1.25-1.86); fresh ET: AOR, 2.87(1.89-4.35). Fresh ET was associated with higher risks for PA (SC: AOR, 2.19(1.51-3.18); FET: AOR, 0.39(0.17-0.90)), SGA (SC: AOR, 1.56(1.06-2.31), FET: AOR, 0.42(0.19-0.91)), and LBW (SC: AOR, 2.24(1.82-2.77), FET: AOR, 0.63 (0.44-0.89)), and fresh ET is an independent risk factor for PA and SGA. Furthermore, the risk of GDM was associated with the biological characteristic of low-fertility patients. Conclusions: Embryo status (fresh or frozen) is a key factor affecting the maternal and neonatal outcomes in ART treatments, while biological characteristics of infertile patients also play a certain role.

Effectiveness of integrated management on hypertension and mortality in rural China: A CHHRS study.

A study was conducted to investigate whether an integrated management (IM) model led by public healthcare providers is effective in reducing cardiovascular disease (CVD)-specific and all-cause mortality rates in low-income rural populations with hypertension. The study recruited 14,234 patients with hypertension aged 18 years or older and allocated them to either an IM group or a usual care (UC) group. During a median follow-up of 48.0 months, the incidences of CVD-specific and all-cause deaths were lower in the IM group than in the UC group. The hazard ratios for CVD-specific mortality and all-cause mortality among patients in the IM group were 0.60 and 0.62, respectively. The results showed that the IM model led by public health providers resulted in clinically significant reductions in CVD-specific and all-cause mortality rates in low-income rural populations with hypertension.

Recent advances in sugar-based AIE luminogens and their applications in sensing and imaging.

Most fluorogens with aggregation-induced emission (AIE) characteristics are hydrophobic and most common sugars are hydrophilic and naturally nontoxic. The combination of AIEgens and sugars can construct glycosyl AIEgens with the advantages of good water-solubility, low fluorescent background and satisfactory biocompatibility. Based on the specific reaction or binding with analytes to change the conjugate system or restrict intramolecular motions, glycosyl AIEgens can be used as powerful tools for detecting bioactive molecules or imaging living cells. In this feature article, we summarize recent advances in sugar-based AIE luminogens and their applications in biosensing and imaging. The sugar units could significantly increase the solubility, biocompatibility, target activity, and chemical modifying capacity and often decrease the background fluorescence of the AIE probes. Corresponding studies not only expand the application fields of AIEgens but also provide effective tools for broad carbohydrate research.

Structure-Activity Relationship Studies Leading to the Discovery of Highly Water-Soluble and Biocompatible Acyclic Cucurbit[n]uril FY-3451 as a Universal Antagonist That Rapidly Reverses Neuromuscular Blocking Agents In Vivo.

The development of a reversal agent that can rapidly reverse clinically used nondepolarizing neuromuscular blocking agents (NMBAs) has long been a challenge. Here, we report the synthesis of a series of highly water-soluble acyclic cucurbit[n]urils (acCBs). Systematic structure-activity relationship studies reveal that introducing two propylidene units on the peripheral benzene rings not only remarkably improves the activity of the corresponding derivative acCB6 (FY 3451) in reversing the neuromuscular block of rocuronium, cisatracurium, vecuronium, and pancuronium, the four clinically used NMBAs, through stable inclusion, but also allows for high water-solubility as well as a maximum tolerated dose (2000 mg/kg on rats). In vivo experiments with rats show that, at the identical dose of 25 mg/kg, for rocuronium, vecuronium, and pancuronium, acCB6 can achieve a recovery time shorter than that of sugammadex for rocuronium and, at the dose of 100 mg/kg, realize comparably rapid reversal for cisatracurium.

H3PO4-Impregnated Covalent Organic Framework Membrane on Separators to Prevent Lithium Metal Anode Dendrite Growth.

Inhibiting the growth of lithium dendrites is crucial for battery safety. For separators, their favorable electrolyte wettability, uniform current density, and high ionic conductivity are beneficial for avoiding Li dendrite growth. In this work, we propose a separator (PA@COF/PP) by modifying a polypropylene separator with H3PO4-functionalized covalent organic frameworks. The uniform channels of the covalent organic frameworks and H3PO4 can homogenize the current and act as ionic conductors for efficient Li+ migration. The synthesized separator effectively suppresses the growth of lithium dendrites and improves the stability of the batteries. A symmetric cell with the PA@COF/PP separator exhibits a stable life span over 4000 hours at a high current density of 5 mA cm-2, compared to the commercial PP separator, which lasts only 159 hours. This work provides an efficient method and novel inspiration for the construction of dendrite-free lithium metal batteries.

Development of Novel Indole-Based Covalent Inhibitors of TEAD as Potential Antiliver Cancer Agents.

Abnormal activation of the YAP transcriptional signaling pathway drives proliferation in many hepatocellular carcinoma (HCC) and hepatoblastoma (HB) cases. Current treatment options often face resistance and toxicity, highlighting the need for alternative therapies. This article reports the discovery of a hit compound C-3 from docking-based virtual screening targeting TEAD lipid binding pocket, which inhibited TEAD-mediated transcription. Optimization led to the identification of a potent and covalent inhibitor CV-4-26 that exhibited great antitumor activity in HCC and HB cell lines in vitro, xenografted human HCC, and murine HB in vivo. These outcomes signify the potential of a highly promising therapeutic candidate for addressing a subset of HCC and HB cancers. In the cases of current treatment challenges due to high upregulation of YAP-TEAD activity, these findings offer a targeted alternative for more effective interventions against liver cancer.

Estimating thresholds of nitrogen, phosphorus and potassium fertilizer rates for rice cropping systems in China.

Determining the fertilization rate plays a pivotal role in agronomic practices as they directly impact yield targets, soil fertility, and environmental risks. In this study, we proposed a method that utilizes allowed ranges of partial nutrient balance and yield to estimate the threshold of nitrogen (N), phosphorus (P), and potassium (K) fertilizer applied to rice (Oryza sativa L.) fields in China. Based on a dataset of 6792 observations from rice fields, we determined the minimum and maximum rates of N, P and K suggested for single (mono-season rice), middle (summer-season rice rotated with winter-season upland crop), early and late (double-season rice cropping system) rice, ranging between 114-146 and 220-292 kg N ha-1 per season, 56-74 and 112-149 kg P2O5 ha-1 per season, and 170-230 and 329-347 kg K2O ha-1 per season, respectively. These values serve as the lower and upper fertilization thresholds, guiding yield goals and environmental protection. Furthermore, if rice straw is returned to fields, the demand for K fertilizer can theoretically decrease by 183 kg K2O ha-1, with corresponding decreases of 50 kg N ha-1 and 26 kg P2O5 ha-1, respectively. A recommended fertilization approach, excluding returned straw nutrients from the upper fertilization thresholds, suggested average application rates of 194 kg N ha-1, 105 kg P2O5 ha-1, and 157 kg K2O ha-1, which align well with the nutrient requirements of rice. Additionally, substituting organic N for chemical N is an effective approach to conserve chemical fertilizer N, potentially reducing chemical N usage by 20%-40%. Utilizing slow-release N is also a favorable option to enhance N use efficiency and optimize N balance. This study offers valuable insights into the development of fertilization restriction indicators, aiming to achieve a delicate balance between environmental impact and agricultural productivity through the adoption of balanced fertilization rates and utilization of organic residues.

Dynamics of glutamine synthetase expression in hepatic ischemia-reperfusion injury: Implications for therapeutic interventions.

BACKGROUND: Hepatic ischemia-reperfusion injury (IRI) poses a great challenge in liver surgery and transplantation because of oxidative stress and inflammatory responses. The changes in glutamine synthetase (GS) expression during hepatic IRI remain unclear. AIM: To investigate the dynamic expression of GS during hepatic IRI. METHODS: Following hepatic ischemia for 1 h and reperfusion, liver tissue samples were collected at 0.5, 6, and 24 hours postreperfusion for fixation, embedding, sectioning. Hematoxylin and eosin staining and GS staining were performed. RESULTS: GS expression rapidly decreases in hepatocytes around the central vein after IRI, reaching its lowest point at 6 hours postreperfusion, and then gradually recovers. CONCLUSION: GS is highly sensitive to IRI, highlighting its potential role as an indicator of liver injury states and a target for therapeutic intervention.

Electronegativity- induced cobalt-doped platinum hollow nanospheres with high CO tolerance for efficient methanol oxidation reaction.

Although Platinum (Pt)-based alloys have garnered significant interest within the realm of direct methanol fuel cells (DMFCs), there still exists a notable dearth in the exploration of the catalytic behavior of the liquid fuels on well-defined active sites and unavoidable Pt poisoning because of the adsorbed CO species (COads). Here, we propose an electronegativity-induced electronic redistribution strategy to optimize the adsorption of crucial intermediates for the methanol oxidation reaction (MOR) by introducing the Co element to form the PtCo alloys. The optimal PtCo hollow nanospheres (HNSs) exhibit excellent high-quality activity of 3.27 A mgPt-1, which is 11.6 times and 13.1 times higher than that of Pt/C and pure Pt, respectively. The in-situ Fourier transform infrared reflection spectroscopy validates that electron redistribution could weak CO adsorption, and subsequently decrease the CO poisoning adjacent the Pt active sites. Theoretical simulations result show that the introduction of Co optimize surface electronic structure and reduce the d-band center of Pt, thus optimized the adsorption behavior of COads. This study not only employs a straightforward method for the preparation of Pt-based alloys but also delineates a pathway toward designing advanced active sites for MOR via electronegativity-induced electronic redistribution.

Determinants of spatiotemporal changes of land use carbon emissions for counties in Shaanxi Province, China.

In China, urban sprawl and developed land expansion challenge the country's "carbon peak" and "carbon neutrality" goals. Counties as the basic governance units are crucial for effective carbon reduction policies. This study examines land use carbon emissions (LUCE) in Shaanxi Province at the county level, essential for China's low-carbon strategy. Analyzing data from 107 counties between 2000 and 2020, we found that developed land, though increasing, is the primary carbon source with a slowing growth rate. The Conversion of Cropland to Forests and Grasslands national policy mitigated the impact on carbon absorption. Carbon emissions displayed positive autocorrelation and spatial heterogeneity, varying across the region. Using the Spatial Durbin Error Model, we linked county-level emissions to GDP per capita, population, urbanization rate, and research and development expenditure for direct and indirect influence. These factors correlate with fossil fuel use and high-quality industrial development. Promoting public transits and reducing private car use are vital for achieving local and regional low-carbon goals.

Multifunctional carbomer based ferulic acid hydrogel promotes wound healing in radiation-induced skin injury by inactivating NLRP3 inflammasome.

BACKGROUND: Radiation-induced skin injury is a significant adverse reaction to radiotherapy. However, there is a lack of effective prevention and treatment methods for this complication. Ferulic acid (FA) has been identified as an effective anti-radiation agent. Conventional administrations of FA limit the reaching of it on skin. We aimed to develop a novel FA hydrogel to facilitate the use of FA in radiation-induced skin injury. METHODS: We cross-linked carbomer 940, a commonly used adjuvant, with FA at concentrations of 5%, 10%, and 15%. Sweep source optical coherence tomography system, a novel skin structure evaluation method, was applied to investigate the influence of FA on radiation-induced skin injury. Calcein-AM/PI staining, CCK8 assay, hemolysis test and scratch test were performed to investigate the biocompatibility of FA hydrogel. The reducibility of DPPH and ABTS radicals by FA hydrogel was also performed. HE staining, Masson staining, laser Doppler blood flow monitor, and OCT imaging system are used to evaluate the degree of skin tissue damage. Potential differentially expressed genes were screened via transcriptome analysis. RESULTS: Good biocompatibility and in vitro antioxidant ability of the FA hydrogels were observed. 10% FA hydrogel presented a better mechanical stability than 5% and 15% FA hydrogel. All three concentrations of FA remarkably promoted the recovery of radiation-induced skin injury by reducing inflammation, oxidative conidiation, skin blood flow, and accelerating skin tissue reconstruction, collagen deposition. FA hydrogel greatly inhibiting the levels of NLRP3, caspase-1, IL-18, pro-IL-1ß and IL-1ß in vivo and vitro levels through restraining the activation of NLRP3 inflammasome. Transcriptome analysis indicated that FA might regulate wound healing via targeting immune response, inflammatory response, cell migration, angiogenesis, hypoxia response, and cell matrix adhesion. CONCLUSIONS: These findings suggest that the novel FA hydrogel is a promising therapeutic method for the prevention and treatment of radiation-induced skin injury patients.

Experimental evaluation of an artificial anal sphincter based on biomechanical compatibility.

BACKGROUND: The artificial anal sphincter is a device used to treat patients with fecal incontinence who are unable to control their bowel movements on their own. Long-term morphological changes in the tissue surrounding the artificial anal sphincter can cause biomechanical compatibility problems, which seriously affect the clinical application of the artificial anal sphincter. METHODS: In this paper, the superelasticity of shape memory alloys was utilized to design and fabricate a biomechanically compatible constant force clamping artificial anal sphincter. An in vitro simulation system was constructed to verify the effectiveness, safety, and constant force characteristics of the artificial anal sphincter. RESULTS: The experimental results demonstrated that the artificial anal sphincter could be effectively closed with no leakage of the liquid-like intestinal contents, which are most likely to leak. The pressure of the artificial anal sphincter on the intestinal tube gradually increased and eventually became constant during closure, and the pressure value was always less than the intestinal blood supply pressure threshold. CONCLUSIONS: In this paper, we designed an artificial anal sphincter based on biomechanical compatibility and the corresponding in vitro simulation experimental program and preliminarily verified the effectiveness, safety, and constant force characteristics of the artificial anal sphincter.

CDH3 Is an Effective Serum Biomarker of Colorectal Cancer Distant Metastasis Patients.

Few robust biomarkers are available for distant metastatic colorectal cancer (CRC) patients. Aberrant high expression of CDH3 has been reported in advanced CRC patients, but the value of CDH3 as a biomarker for the diagnosis and prognosis of distant metastatic CRC patients remains to be evaluated. In this study, we explored the serum levels of CDH3 in different stages of CRC patients and sought to determine whether serum CDH3 serves as an independent biomarker for distant metastatic CRC patients. We analyzed the serum CDH3 levels by ELISA in a cohort of CRCs (n=96) and normal controls (n=28). We compared the serum CDH3 levels between normal controls and different stages of CRCs. As a potential diagnostic marker of distant metastatic CRC, the specificity and sensitivity of serum CDH3 were evaluated. Multivariate analysis was also performed to determine whether serum CDH3 was an independent risk factor. Moreover, the changes of serum CDH3 levels were monitored and analyzed before and after palliative chemotherapy. Serum levels of CDH3, CA24-2, CA19-9, CA72-4, and CEA were significantly elevated in distant metastatic CRCs. CA24-2 (r=0.24, P=0.01), CA19-9 (r=0.20, P=0.03), CA72-4 (r=0.64, P<0.0001), and CEA (r=0.31, P=0.0012) all had a certain correlation with CDH3. After three cycles of palliative chemotherapy, levels of CDH3, CA24-2, CA19-9, CA72-4, and CEA of partial response CRCs were reduced to 38.8% (95% confidence interval [CI]: 30.95%-53.77%), 57.73% (95% CI: 2.085%-73.83%), 50.33% (95% CI: 9.935%-79.42%), 74.74% (95% CI: 25.21%-88.00%), and 59.16% (95% CI: 12.65%-83.56%) of baseline, respectively. The areas under the receiver operating characteristic curves of CDH3, CA24-2, CA19-9, CA72-4, and CEA with chemotherapy response were 0.900, 0.597, 0.635, 0.608, and 0.507, respectively. Serum CDH3 is an effective serum biomarker for the diagnosis of distant metastatic CRCs and monitoring response to palliative chemotherapy in distant metastatic CRCs.

Clinical Implications of Left Ventricular Apex Mechanics in Patients with Apical Hypertrophic Cardiomyopathy.

BACKGROUND: Apical hypertrophic cardiomyopathy (ApHCM) is a unique disease with pathological hypertrophy mainly at the left ventricular (LV) apex. Although previous studies have indicated apical dysfunction in ApHCM, how apical mechanics change during disease progression has not been thoroughly examined. We aimed to characterize the mechanics of the LV apex in ApHCM patients at different disease stages and explore the clinical significance of these alterations. METHODS: 104 ApHCM patients were divided into 3 subtypes based on LV apical maximum wall thickness (AMWT) and extent of hypertrophy: relative-type (isolated apical hypertrophy with AMWT <15 mm), pure-type (isolated apical hypertrophy with AMWT ≥15 mm), and mixed-type (both apical and midventricular hypertrophy with AMWT ≥15 mm). Two-dimensional speckle-tracking echocardiography was used to analyze LV segmental strain, global strain, and twist. Comparisons of these parameters were performed among ApHCM subtypes and 30 healthy controls. Logistic regression and Cox proportional hazard regression analyses were employed to explore associations between myocardial mechanics and clinical indicators. A composite outcome of new-onset atrial fibrillation, heart failure hospitalization, myectomy, and all-cause mortality was assessed. RESULTS: Even in relative ApHCM patients, apical longitudinal strain (LS), circumferential strain (CS), and radial strain (RS) were significantly impaired compared to controls (LS: -14.6±4.1% vs.-20.0±1.7%, p=0.001; CS: -19.6±2.5% vs.-25.6±3.7%, p=0.002; RS: 26.6±7.4% vs. 35.6±11.1%, p=0.026), while apical rotation and LV twist remained unchanged. In patients with greater apical hypertrophy (mixed and pure patients), apical LS and RS were more abnormal. Moreover, apical rotation showed significant reductions compared to relative-type patients. After adjusting for clinical and myocardial mechanical parameters, apical rotation was independently associated with NYHA class ≥ II (odds ratio =0.81, 95% confidence interval [CI]: 0.66-0.99, p=0.036) and the composite outcome (hazard ratio =0.82, 95% CI: 0.73-0.91, p=0.001). CONCLUSIONS: Relative ApHCM demonstrates apical dysfunction but sparing of apical rotation, which was abnormal in more extensive phenotypes. LV apex mechanics were closely related to clinical patterns, with apical rotation correlated with both NYHA class ≥ II and clinical events.

Evolution of Karst Geothermal Hydrochemical Characteristics and Genesis Mechanism in Northern Jinan, Shandong, Eastern China.

The study of geothermal water hydrochemical characteristics and solute transport evolution can provide a reliable hydrogeochemical basis for the development and protection of geothermal resources. Currently, there is a lack of systematic research on the hydrochemical evolution mechanism of geothermal fields in northern Jinan, which limits the development and use of geothermal fields. In this study, the hydrochemical properties of groundwater in northern Jinan were described by analyzing the hydrochemical characteristics of 16 geothermal water samples and 3 cold water samples. The results show that during the transformation from cold water in the south to geothermal water in the north, the contents of major ions all show an increasing trend and the hydrochemical characteristics show obvious zoning characteristics. The hydrochemical type evolved from HCO3-Ca to HCO3-Ca·Mg type, and then further evolved SO4-Ca and SO4-Ca·Na type water. Dissolution-precipitation of carbonate, sulfate, halite, and silicate minerals is one of the important processes that controls the chemical characteristics of geothermal water. The water source is mainly from the atmospheric precipitation in the Taiyi Mountain, with an altitude of 698.99-1464.91 m.s.a.l. The thermal reservoir temperature in the study area is estimated to be 55.62-98.16 °C. This paper proposes a conceptual model of the karst geothermal water flow system in northern Jinan, which provides a new idea for exploring the geothermal water genesis mechanism under similar geological conditions.

The role of botanical triterpenoids and steroids in bile acid metabolism, transport, and signaling: Pharmacological and toxicological implications.

Bile acids (BAs) are synthesized by the host liver from cholesterol and are delivered to the intestine, where they undergo further metabolism by gut microbes and circulate between the liver and intestines through various transporters. They serve to emulsify dietary lipids and act as signaling molecules, regulating the host's metabolism and immune homeostasis through specific receptors. Therefore, disruptions in BA metabolism, transport, and signaling are closely associated with cholestasis, metabolic disorders, autoimmune diseases, and others. Botanical triterpenoids and steroids share structural similarities with BAs, and they have been found to modulate BA metabolism, transport, and signaling, potentially exerting pharmacological or toxicological effects. Here, we have updated the research progress on BA, with a particular emphasis on new-found microbial BAs. Additionally, the latest advancements in targeting BA metabolism and signaling for disease treatment are highlighted. Subsequently, the roles of botanical triterpenoids in BA metabolism, transport, and signaling are examined, analyzing their potential pharmacological, toxicological, or drug interaction effects through these mechanisms. Finally, a research paradigm is proposed that utilizes the gut microbiota as a link to interpret the role of these important natural products in BA signaling.

The significance of ferroptosis in renal diseases and its therapeutic potential.

Kidney diseases are significant global public health concern, with increasing prevalence and substantial economic impact. Developing novel therapeutic approaches are essential for delaying disease progression and improving patient quality of life. Cell death signifying the termination of cellular life, could facilitate appropriate bodily development and internal homeostasis. Recently, regulated cell death (RCD) forms such as ferroptosis, characterized by iron-dependent lipid peroxidation, has garnered attention in diverse renal diseases and other pathological conditions. This review offers a comprehensive examination of ferroptosis, encompassing an analysis of the involvement of iron and lipid metabolism, the System Xc - /glutathione/glutathione peroxidase 4 signaling, and additional associated pathways. Meanwhile, the review delves into the potential of targeting ferroptosis as a therapeutic approach in the management of acute kidney injury (AKI), chronic kidney disease (CKD), diabetic nephropathy, and renal tumors. Furthermore, it emphasizes the significance of ferroptosis in the transition from AKI to CKD and further accentuates the potential for repurposing drug and utilizing traditional medicine in targeting ferroptosis-related pathways for clinical applications. The integrated review provides valuable insights into the role of ferroptosis in kidney diseases and highlights the potential for targeting ferroptosis as a therapeutic strategy.