BACKGROUND:Post cardiac arrest brain injury (PCABI) results from global ischemia-reperfusion. Circular RNAs (circRNAs) are stable regulators of post transcriptional networks that may modulate neuronal survival and metabolism after ischemic injury. We investigated the role and mechanism of mmu_circ_0000376 (circ_0000376) in PCABI. METHODS:Through integrated bioinformatics analysis of circular RNA/microRNA/messenger RNA datasets via the GEO platform, a regulatory network involving circ_0000376/mmu-let-7b-5p/CCND1 was identified. We validated its circular structure, stability, and cytoplasmic localization in HT22 neuronal cells. Through in vitro and in vivo experiments modulating circ_0000376 expression, we investigated cellular functions by assessing cell viability, apoptosis (Annexin V/PI staining, TUNEL, caspase/Bcl-2 family proteins), and mitochondrial/energy parameters (ATP, glucose consumption, lactate, G6PD activity). RESULTS:Circ_0000376 is a stable, cytoplasmic circRNA. Overexpression of Circ_0000376 reduced ischemia-reperfusion injury induced ROS, preserved ATP and glycolytic flux, increased G6PD activity, decreased apoptosis, and restored CCND1 and Bcl 2 while lowering Bax and cleaved caspases. Bioinformatic and reporter assays showed circ_0000376 sponges mmu-let-7b-5p, relieving repression of CCND1. mmu-let-7b-5p overexpression or CCND1 knockdown reversed circ_0000376 mediated protection. AAV mediated circ_0000376 overexpression in mice decreased hippocampal apoptosis and restored CCND1 in vivo. CONCLUSIONS:Circ_0000376/mmu-let-7b-5p/CCND1 axis mitigates neuronal apoptosis and metabolic dysfunction after ischemic injury. Targeting this ceRNA network may offer a novel neuroprotective strategy for PCABI.
Delirium is a common complication in patients with hemorrhagic stroke (HS) admitted to intensive care, but its association with peripheral oxygen saturation (SpO2) remains uncertain. We analyzed 1935 adults with HS from the Medical Information Mart for Intensive Care IV (MIMIC-IV, v3.1). SpO2 was recorded and categorized as low (<95%), moderate (95-98%), or high (>98%) after intensive care unit (ICU) admission. Delirium was identified using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Associations were assessed with multivariable logistic regression, restricted cubic spline (RCS) modeling, subgroup analyses, and receiver operating characteristic (ROC) curves for SpO2, Glasgow Coma Scale (GCS), and their combination. Delirium occurred most frequently in the high SpO2 group (29.6%), followed by the low (19.7%) and moderate groups (17.6%). Compared with the moderate group, high SpO2 was consistently associated with increased delirium risk (adjusted odds ratio: 1.855-1.998; all P < .001), while low SpO2 showed no independent association. RCS analysis demonstrated a U-shaped relationship with the lowest risk between 95% and 98%. Subgroup analyses confirmed consistency across patient characteristics. Combining SpO2 with GCS improved prediction (AUC = 0.702) compared with either alone. High SpO2 (>98%) was independently associated with increased delirium risk, while low SpO2 (<95%) showed a nonlinear trend but was not statistically significant in fully adjusted categorical models. Maintaining SpO2 around 95% to 98% and integrating SpO2 with GCS may aid early risk stratification.
BACKGROUND:Out-of-hospital cardiac arrest (OHCA) in China has a high incidence and poor survival, highlighting an urgent need for rapid identification of reversible aetiologies. Conventional transthoracic echocardiography during resuscitation can be limited by imaging quality and prolonged chest compression interruptions. Transoesophageal echocardiography (TEE) is a feasible alternative that allows for continuous real-time imaging during compressions, but its utility in Chinese OHCA patients remains uncertain. METHODS:This prospective, single-centre exploratory study enrolled 45 consecutive selected adults with non-traumatic OHCA (NT-OHCA) of unclear aetiology who were eligible for TEE. Of all enrolled patients, 43 completed standardised TEE image acquisition, while 2 cases with TEE-unrecognisable aetiology were excluded from aetiological analysis. The per-protocol analysis finally included 41 patients in whom TEE was successfully completed. Certified emergency physicians performed simplified TEE examinations (five standard views) during active resuscitation. Door-to-TEE interval, diagnostic yield, TEE-guided interventions and clinical outcomes were recorded according to Utstein guidelines. RESULTS:TEE yielded diagnostic-quality images in all patients (43/43), with a median door-to-TEE time of 13 min (IQR: 6.5-22). Reversible aetiologies were identified in 39.0% (16/41), most commonly acute aortic dissection (50.0%, 8/16), followed by massive pulmonary embolism (25.0%), hypertrophic cardiomyopathy (18.8%) and hypovolaemia (6.3%). TEE guided interventions in 56.3% (9/16) of identified cases. Return of spontaneous circulation (ROSC) and 28-day survival rates were 41.5% and 12.2%, respectively, with no significant differences between aetiology-identified and unidentified groups (ROSC: 37.5% vs 44.0%, p>0.05; 28-day survival: 6.3% vs 16.0%, p>0.05). Sensitivity analysis of the 43-case complete imaging cohort and the total 45 enrolled cases further verified the stability and reliability of the diagnostic results. CONCLUSIONS:During mechanical cardiopulmonary resuscitation, TEE rapidly identified suspected aetiologies in 39% (16/41) of NT-OHCA cases, notably revealing frequent acute aortic dissections. Lacking a comparator group, TEE's feasibility as a complementary tool requires further controlled investigation.
Acute pancreatitis (AP)-induced intestinal barrier disruption drives fatal systemic complications. We engineered human umbilical cord mesenchymal stem cell-derived extracellular vesicles (hUC-MSC-EVs) to deliver emodin-a bioactive compound limited by poor bioavailability-for targeted intestinal protection. In TNF-α-stimulated intestinal epithelial cells (CCD-841CON), EV-loaded emodin (EVs-Emodin) synergistically suppressed NLRP3 inflammasome activation, pyroptosis, reactive oxygen species production, and inflammatory cytokines, outperforming monotherapies. EVs-Emodin restored cell viability and curtailed apoptosis. In taurocholate-induced AP mice, intravenous EVs-Emodin attenuated systemic inflammation, promoted the expression of Occludin and ZO-1, mitigated intestinal tissue lesions, promoted epithelial regeneration, inhibited inflammasome activation, and alleviated mitochondrial damage. hUC-MSC-EVs overcome emodin's delivery limitations, providing a synergistic strategy to protect the intestinal barrier via NLRP3/pyroptosis inhibition and oxidative stress mitigation, offering a promising therapeutic approach for AP-associated intestinal injury.
Background Sepsis complicates acute pancreatitis (AP), increasing mortality risk. Few studies have examined how sepsis and its onset timing affect mortality in AP. This study evaluates the association between sepsis occurrence and all-cause mortality in AP, focusing specifically on the impact of sepsis onset timing. Methods This multicenter retrospective cohort study included 494 ICU-admitted AP patients from the MIMIC-IV database and 91 from our center. Patients were grouped by sepsis occurrence and onset timing. Clinical outcomes were in-hospital and 90-day all-cause mortality. Machine learning identified key variables associated with mortality. Multivariable regression analyzed the impact of sepsis and its onset timing on mortality. To reduce baseline differences, propensity score matching (PSM) based on time to sepsis was conducted. After PSM, Kaplan-Meier survival analyses incorporated data from our center for validation. Restricted cubic spline analysis examined any nonlinear relationship between sepsis onset timing and mortality. Results Patients with sepsis had significantly higher in-hospital and 90-day mortality rates than those without sepsis ( p < 0.05). Sepsis was identified as a significant risk factor for in-hospital mortality and remained significantly associated after adjusting for key variables ( p < 0.05). However, sepsis onset timing did not significantly impact in-hospital or 90-day mortality. These findings were validated after PSM and with our center's data. No nonlinear relationship between sepsis onset timing and mortality was found. Conclusion Sepsis significantly increases all-cause mortality in AP patients, but the timing of its onset has limited impact. Continuous monitoring and intervention for sepsis during hospitalization are recommended to improve prognosis.
Although insulin is widely used for early lipid lowering in hypertriglyceridemic acute pancreatitis, the clinical benefit of heparin combined with insulin remains unclear. To examine whether low-molecular-weight heparin (LMWH) combined with insulin is superior to insulin alone in improving clinical outcomes in hypertriglyceridemic acute pancreatitis. This multicenter, open-label, parallel-group, superiority randomized clinical trial was conducted from September 21, 2019, to April 2, 2023, across 13 tertiary hospitals in China. The duration of follow-up was 30 days after randomization. Patients aged 18 to 85 years were eligible if they met the diagnostic criteria for acute pancreatitis, presented with baseline serum triglyceride levels between 1000 and 3550 mg/dL, and were admitted within 48 hours of symptom onset. Participants received either subcutaneous LMWH (4000 IU every 12 hours for 3 days) plus insulin (LMWH plus insulin group) or insulin alone (insulin group). The primary end point was a composite of new-onset organ failure (defined as organ failure occurring after randomization but absent during the 24-hour prerandomization period) and/or all-cause mortality within 30 days after randomization. Among 533 randomized patients (median [IQR] age, 39 [33-46] years; 406 [76.2%] male), 264 were randomized to LMWH plus insulin and 269 to insulin alone. The primary end point occurred in 66 (25.0%) of the LMWH and insulin group vs 76 (28.3%) of the insulin group (relative risk [RR], 0.89; 95% CI, 0.67-1.17; P = .40). Both groups achieved the triglyceride target (<500 mg/dL) in a median (IQR) of 2 (1-3) days ( P = .94). Safety outcomes were similar between groups, including new-onset bleeding events (RR, 0.61; 95% CI, 0.15-2.53; P = .73), triglyceride rebound (RR, 0.53; 95% CI, 0.28-1.01; P = .05), and drug-related adverse events (RR, 0.79; 95% CI, 0.30-2.10; P = .64). In this randomized clinical trial, the combination of LMWH and insulin failed to demonstrate superior efficacy vs insulin alone in patients with hypertriglyceridemic acute pancreatitis. LMWH might not be necessary for early lipid-lowering in hypertriglyceridemic acute pancreatitis. ChiCTR.org.cn Identifier: ChiCTR1900023640
The Bayan Har block, one of China's most seismically active regions, has experienced multiple major earthquakes (≥M 7.0) in recent years. It is a key area for investigating the interactions between the Qinghai-Xizang (Qingzang) Plateau and adjacent blocks, plateau uplift, and strong earthquake mechanisms. P-wave velocity and crustal composition provide key constraints on the properties of distinct tectonic units and their evolutionary modification processes. Based on the results of 8 Deep Seismic Sounding (DSS) profiles completed in the Bayan Har block and surrounding areas over the past 20 years, We constructed one-dimensional P-wave velocity models for the crust of Bayan Har block, Qilian fold belt, Qinling fold belt, Alxa block, Ordos block and Sichuan basin. Furthermore, crustal composition models for different tectonic units were established based on these results. The results reveal that the crustal thickness of the Bayan Har block gradually decreases towards the NNE, NE, and SE directions, while the average crustal velocity increases correspondingly. The felsic layer in the crust accounts for more than half of the total crustal thickness. The mafic content within the crust of different tectonic units exhibits notable variations, which may reflect that the Bayan Har block, Qilian fold belt, and Qinling fold belt have experienced more intensive lithospheric evolution processes compared to Ordos basin and Sichuan basin. The seismicity distribution in this region is significantly controlled by crustal velocity and composition heterogeneity across the Bayan Har block and adjacent areas, which demonstrates that earthquakes within and around the Bayan Har block exhibit both high frequency and larger magnitudes. These seismic characteristics primarily result from intense crustal stress accumulation and release during the outward expansion of the Qingzang Plateau.
Acute pancreatitis (AP) frequently leads to acute lung injury, a major contributor to AP-related mortality. Emodin, a natural anti-inflammatory compound, shows therapeutic promise. Human umbilical cord mesenchymal stem cell-derived extracellular vesicles (hUC-MSC-EVs) also exhibit intrinsic therapeutic properties against AP-associated lung injury. This study investigated whether encapsulating emodin into these EVs (EVs-Emodin) enhances their protective effects in alleviating lung injury caused by AP-triggered systemic inflammation.EVs-Emodin were encapsulated into hUC-MSC-EVs and compared with free emodin in vitro using TNF-α-treated BEAS-2B lung epithelial cells and in vivo using a sodium taurocholate (STC)-induced AP mouse model. Cell viability, apoptosis, ROS production, inflammatory cytokine release, mitochondrial morphology, and pyroptosis markers were assessed using CCK-8, flow cytometry, ELISA, qPCR, transmission electron microscopy, Western blotting, and immunostaining.EVs-Emodin exhibited effective uptake and significantly improved BEAS-2B cell viability compared to emodin or hUC-MSC-EVs alone. They also more effectively reduced TNF-α-induced apoptosis, ROS accumulation, inflammatory cytokine production, and pyroptotic signaling. In AP mice, EVs-Emodin administration is more efficient in preserving lung tissue structure, restoring lung epithelial proliferation, and reducing inflammation and pyroptosis.Encapsulation of emodin in hUC-MSC-EVs significantly enhances their therapeutic efficacy against AP-induced lung injury. EVs-Emodin represent a promising strategy for targeted treatment of inflammatory complications in AP.
BACKGROUND:Acute pancreatitis (AP) is a complex condition requiring immediate treatment. Both extracellular vesicles derived from human umbilical cord mesenchymal stem cells (hUC-MSC-EVs) and emodin, a naturally occurring anthraquinone used in traditional Chinese medicine, have shown therapeutic potential in treating AP. However, the mechanisms by which hUC-MSC-EVs and emodin alleviate AP, and whether they exert a synergistic effect on inflamed pancreatic tissues, remain unclear. OBJECTIVE:Our study aimed to evaluate the efficacy of emodin, hUC-MSC-EVs, and their combination in AP, explore synergistic mechanisms, and propose hUC-MSC-EVs as a novel drug delivery strategy for therapeutic applications. DESIGN:In this study, we developed AP cell, organoid, and animal models to compare the effects of emodin, hUC-MSC-EVs, and emodin-loaded hUC-MSC-EVs on cell viability, inflammation, and pyroptosis. RESULTS:Our data revealed that all three treatments improved cell viability, reduced pro-inflammatory cytokine expression, and inhibited pyroptosis in the AP models. Notably, the encapsulation of emodin significantly enhanced the protective effects of hUC-MSC-EVs.These findings suggest that emodin's protective effects on inflamed pancreatic tissues may be attributed, at least in part, to its anti-inflammatory and anti-pyroptotic properties. Additionally, our study proposes a novel strategy for engineering hUC-MSC-EVs for potential therapeutic applications in AP treatment.
Due to the lack of the three-dimensional structure of the Zhaoji Salt Basin, the salt mining enterprises have obvious clustering when choosing sites. Production capacity declines rapidly as mining deepens, and the enterprises are entering a stage of stagnation in production. In this study, a dense seismic array of 125 short-period stations was deployed around the core mining area and its vicinity of the salt mine industry, we used the ambient noise tomography (ANT) method to image the three-dimensional shear wave velocity structure at the depth shallower than 3 km. The results indicate: (1) The overall shear wave velocity in the study area is relatively lower, ranging from 0.8 to 1.8 km/s, which could be related to the loose and thick deposition of the Zhaoji sub-depression. (2) The three-dimensional shear wave velocity structure reveals that the sedimentary thickness of the Zhaoji sub-depression is deeper in the southeast and shallower in the northwest, with the sedimentary center located around Heping Town and Dahuangzhuang Town. (3) The Zhaoji salt mine is a low-velocity anomalous zone in the shear wave velocity structure with an inverse ‘C’ character spreading along Nanchenji Town and Zhaoji Town, with a depth ranging from approximately 1.2 to 2.8 km, it may be caused by the development of rock fissures due to water extraction and injection. The surrounding rock exhibits relatively high velocity, which reflects the morphological characteristics of the Zhaoji Salt Basin. The three-dimensional shear wave velocity model obtained in this study provides scientific guidance for the industrial exploitation of the Zhaoji salt mine and reference for salt exploration of the Hongze Salt Basin. It also provides an important basis for the seismic risk assessment of the salt basins. Simultaneously, it holds significant implications for exploring the application of ambient noise tomography method in spatial detection of salt mine belt.
BACKGROUND:This study aimed to explore the risk factors associated with intensive care unit-acquired weakness (ICU-AW) in critically ill patients at risk of malnutrition and to evaluate the efficacy of early enteral nutrition (EEN) and the role of biomarkers in managing ICU-AW. METHODS:This retrospective, observational cohort study included 180 patients at risk of malnutrition admitted to the emergency intensive care unit of the First Affiliated Hospital of Xiamen University Hospital from January 2022 to December 2023. Patients were divided into ICU-AW group and non-ICU-AW group according to whether they developed ICU-AW, or categorized into EEN and parenteral nutrition (PN) groups according to nutritional support. ICU-AW was diagnosed using the Medical Research Council score. The primary outcome was the occurrence of ICU-AW. RESULTS:The significant factors associated with ICU-AW included age, sex, type of nutritional therapy, mechanical ventilation (MV), body mass index (BMI), blood urea nitrogen (BUN), and creatinine (Cr) levels (P<0.05). The PN group developed ICU-AW earlier than did the EEN group, with a significant difference observed (log-rank P<0.001). Among biomarkers for ICU-AW, the mean prealbumin (PAB)/C-reactive protein (CRP) ratio had the highest diagnostic accuracy (area under the curve [AUC] 0.928, 95% confidence interval [95% CI] 0.892-0.946), surpassing the mean Cr/BUN ratio (AUC 0.740, 95% CI 0.663-0.819) and mean transferrin levels (AUC 0.653, 95% CI 0.574-0.733). CONCLUSION:Independent risk factors for ICU-AW include female sex, advanced age, PN, MV, lower BMI, and elevated BUN and Cr levels. EEN may potentially delay ICU-AW onset, and the PAB/CRP ratio may be an effective diagnostic marker for this condition.
BACKGROUND:Fluid resuscitation in acute pancreatitis (AP) patients requires precise titration because both excess and insufficient volumes may worsen outcomes. This study aimed to develop a weight-normalized fluid balance index (FBI) and assess its association with in-hospital mortality in critically ill AP patients. METHODS:This retrospective cohort study utilized data from the MIMIC-IV 3.0 database and the emergency intensive care unit (EICU) of our hospital (validation cohort) and was based on inclusion and exclusion criteria. Using the R package cutoff, an FBI of 145 mL/kg was identified as the optimal risk stratification threshold. The primary outcome was in-hospital all-cause mortality. Machine learning was used to screen covariates for inclusion in multivariable Cox models. Cox regression and restricted cubic spline (RCS) models were used to evaluate the relationship between FBI and mortality. Propensity score matching (PSM) was applied to minimize baseline confounding. After PSM, Kaplan-Meier survival curves were generated, and the results were validated via data from our center. RESULTS:In this study, 547 AP patients from the MIMIC-IV database and 156 from the EICU of our hospital were included. In the MIMIC-IV cohort, the overall in-hospital mortality rate was 8.96%. Patients with FBI ≥145 mL/kg had significantly higher in-hospital mortality than did those with FBI <145 mL/kg (P<0.05). High-risk classification remained an independent predictor of death after full adjustment (hazard ratio [HR] 1.99, 95% confidence interval [95% CI]: 1.08-3.69). Post-PSM Kaplan-Meier analysis confirmed significantly higher in-hospital mortality in the high-risk group (P<0.05). This result was corroborated by our validation cohort. RCS analysis further demonstrated a non-linear increase in in-hospital mortality with increasing FBI values. CONCLUSION:An FBI ≥145 mL/kg may be associated with increased in-hospital mortality in critically ill AP patients.
Background:Intestinal ischemia/reperfusion (II/R) is a severe condition with high mortality and limited treatment options. Extracellular vesicles that are derived from bone marrow mesenchymal stem cells (BM-MSC-EVs) exhibit therapeutic potential in alleviating II/R injury. However, the mechanism by which BM-MSC-EVs fulfill this function requires further characterization. The ubiquitin-proteasome system plays an essential role in II/R, but the functions of individual ubiquitination regulators such as ubiquitin-specific proteases (USPs) in this process remain incompletely understood. Methods:An II/R cellular model was established by using IEC-6 intestinal epithelial cells with oxygen-glucose deprivation/reperfusion (OGD/R) treatment. The expression of USPs was evaluated by using quantitative polymerase chain reaction and Western blot. The role of USP38 on the viability, apoptosis, migration, and reactive oxygen species (ROS) levels in OGD/R-treated IEC-6 cells were measured by using CCK-8, Annexin V/PI staining, transwell assay, and 2',7'-dichlorofluorescin diacetate (DCFDA) staining, respectively. The interaction between USP38 and BIRC5 was explored by using co-immunoprecipitation (Co-IP) and the ubiquitination level and stability of BIRC5 were examined by using Western blot. USP38-overexpressing BM-MSC-EVs were produced to treat OGD/R-treated IEC-6 cells. Results:USP38 expression was significantly downregulated in OGD/R-treated IEC-6 cells. Incubation of these cells with BM-MSC-EVs substantially elevated the USP38 expression, resulting in improved viability, reduced apoptosis, enhanced migration, and decreased ROS levels. Furthermore, overexpression of USP38 in BM-MSC-EVs further enhanced their protective effect on OGD/R-treated IEC-6 cells. At the molecular level, USP38 interacts with and stabilizes BIRC5 by decreasing its ubiquitination. Knock-down of BIRC5 abolished the protective effect of excessive USP38 on OGD/R-treated IEC-6 cells. Conclusion:USP38 protects intestinal epithelial cells from I/R injury by enhancing the stability of BIRC5.
ABSTRACT The triglyceride–glucose body mass index (TyG‐BMI) is an emerging composite metabolic indicator in cardiovascular research. However, the link between TyG‐BMI and target organ damage (TOD) in essential hypertension (EH) remains uncertain. This study investigated the association between TyG‐BMI and TOD in patients with EH. We conducted a retrospective cohort study involving 493 individuals with EH. Participants were divided at the cohort‐specific median into high and low TyG‐BMI groups. Over a median follow‐up of 23 months, 191 participants experienced TOD. Kaplan–Meier curves showed a significantly higher cumulative incidence of TOD in the high TyG‐BMI group than in the low TyG‐BMI group ( p < 0.05). In multivariable logistic regression, TyG‐BMI remained an independent correlate of TOD (adjusted OR = 1.83, 95% CI: 1.08–3.10; p < 0.05). Least absolute shrinkage and selection operator–Cox regression further selected TyG‐BMI, age, and smoking status as key predictors of TOD. Subgroup analyses revealed that the TyG‐BMI–TOD association was stronger among younger or middle‐aged, normal‐weight, non‐diabetic, non‐smoking subjects ( p < 0.05). Finally, the TyG‐BMI‐based model achieved predictive accuracy comparable to that of a conventional risk‐factor model. In conclusion, TyG‐BMI is independently associated with TOD in EH patients. Its predictive value closely mirrors that of combined traditional risk factors, highlighting TyG‐BMI as a promising clinical marker.
Guangzhou-Foshan area is located in the heartland of the Pearl River Delta economic zone. Three regional faults intersect each other and pass through this area. The fine 3D shallow S-wave velocity structure in Guangzhou-Foshan area is of great significance for urban planning and construction, earthquake disaster assessment, strong ground motion simulation of this area. In this study, we used the continuous waveform data recorded by 1104 short -period seismometers deployed in a dense seismic array in Guangzhou-Foshan area and calculated the cross -correlation functions between station pairs from the vertical component ambient noise data. 39488 high-quality surface wave group velocity dispersion curves with a period of 0. 1 similar to 5 s are further extracted. And then, the shallow crustal velocity structure in the depth range of 0. 3 similar to 3 km is imaged by the direct surface-wave invert method based on ray tracing. The results show that there are significant velocity variations in the study area. The S-wave velocity structure in the Pearl River Delta is relatively complex, while it is relatively simple in the Guanghua basin. The low-speed anomalies in the study area are mainly located near the faults, at the same time in the falling plate of the faults. The eastern margin of Sanshui Basin in the Pearl River Delta shows a saddle shaped low-speed anomaly, which extends down to 2 km. The South and North boundaries of the low-speed body are basically consistent with the location of the basin controlling faults. There are two parallel high-speed anomalies in Guanghua basin, with a low-speed anomaly parallel to the basin tectonic strike in the middle. The overall velocity structure characteristics are consistent with the geological tectonic background of Guanghua basin as a compound syncline. The low-speed anomaly extends down to a depth of 1. 4 km, which may suggest the maximum burial depth of the stratum involved in the syncline. Long strip-shaped low-speed anomaly is generally developed along the Guangzhou-Conghua fault, which is related to the sedimentary strata formed along the fault. The anomaly is divided into two sections in the shallowarea, indicating that the Guangzhou-Conghua fault may have segmental activity in history. The Yudai park is surrounded by high-speed anomalies, which extend upward to a distance of 1. 3 km from the surface. Combined with the existing geological and geophysical data in the study area, it is speculated that the high-speed anomaly may be a reflection of early magma intrusion in the shallow crust.
Abstract The left‐lateral Altyn Tagh Fault (ATF) system is the northern boundary of the Tibetan Plateau resulted from the India–Eurasia continental collision. How intracontinental deformation across the central ATF responds to the distal collision remains elusive, primarily due to unclear crustal structure. We obtained detailed crustal structure across the central ATF using receiver functions recorded by ∼NW–SE oriented linear dense array. The images reveal the Tarim lower crust is underthrusting beneath the Tibetan Plateau and reaches to a maximum depth of ∼75 km and undergoing partial eclogitization. The two south‐dipping interfaces imaged beneath the Altyn Tagh Range (ATR) represent the thrusting Northern Altyn Fault and its branch fault. Oblique convergent forces extruded upper crustal materials along the thrust faults, creating the pop‐up structure of ATR, supported by low Vp/Vs ratios. Our balanced cross‐section for the Moho suggests intracontinental deformation in the ATR has accelerated since the late Miocene.
Imaging the detailed structure of sedimentary basins is crucial for natural resource exploration and essential for better analysis and correction of sediment responses when studying deeper interior earth structures using seismic data. In the Tarim Basin, previous studies on the sedimentary structures are mostly obtained by active-source seismic surveys, which can provide high-resolution underground interface information but are highly costly or environmentally unfriendly. In this paper, ambient noise tomography, an efficient and economical method based on background vibration, is employed to construct the sedimentary velocity structure at the southeast margin of the Tarim Basin. Based on ambient noise data collected from a linear dense short-period seismic array, we extract Love wave signals from T-T component cross-correlation functions (CCFs) and measure Love wave dispersion curves at a period band of similar to 0.3-11.5 s. Then, we utilize a one-step direct surface wave tomography method to image a fine 2-D sedimentary shear wave velocity structure with a depth reaching 10 km. Our results reveal a clear layered sedimentary structure, the palaeo Tadong uplift and the thrust Cherchen fault. Our study provides reference sedimentary velocity models for the southeastern Tarim Basin, focusing on depths shallower than 10 km. This model is intended to serve as crucial input for studies requiring detailed shallow sedimentary velocity data. Moreover, our research demonstrates that the application of the ambient noise tomography method with dense arrays has great potential for enhancing resource exploration efforts in sedimentary basins.
Obesity poses significant health risks and can negatively impact an individual's quality of life. The human obesity phenotype results from the differentiation of pre-adipocytes into adipocytes, which leads to hypertrophy and hyperplasia in adipose tissue. The molecular mechanisms by which long non-coding RNAs (lncRNAs) modulate adipocyte differentiation, a process implicated in obesity development, remain poorly characterized. A lncRNA which suppressed the hepatic gluconeogenesis and lipogenesis (lncSHGL) was newly identified. Our research aims to elucidate the functional role and mechanistic underpinnings of suppressor of lncSHGL in adipocyte differentiation. We observed that lncSHGL expression progressively diminished during 3T3-L1 differentiation and was downregulated in the liver and perirenal adipose tissue of ob/ob mice. lncSHGL acts as a molecular sponge for miR-149, with Mospd3 identified as a target of miR-149.Overexpression of lncSHGL and inhibition of miR-149 led to suppressed 3T3-L1 proliferation, decreased lipid droplet accumulation, and attenuated promoter activity of PPARγ2 and C/EBPα. These changes consequently resulted in reduced expression of Cyclin D1, LPL, PPARγ2, AP2, and C/EBPα, as well as inhibited the PI3K/AKT/mTOR signaling pathway. In contrast, lncSHGL suppression yielded opposing outcomes. Moreover, the effects of lncSHGL overexpression and miR-149 inhibition on reduced expression of Cyclin D1, LPL, PPARγ2, AP2, and C/EBPα were reversible upon miR-149 overexpression and Mospd3 suppression. These findings were further validated in vivo. We also discovered a significant increase in methylation levels during 3T3-L1 differentiation, with lncSHGL highly expressed in the presence of a methylation inhibitor. In conclusion. lncSHGL methylation facilitates adipocyte differentiation by modulating the miR-149/Mospd3 axis. Targeting lncSHGL expression may represent a promising therapeutic strategy for obesity-associated adipogenesis, particularly in the context of fatty liver disease.
Abstract Endothelial dysfunction is acknowledged as a marker for subclinical target organ damage (STOD) in hypertension, though its therapeutic potential has not yet been clarified. This study assessed whether early endothelial function improvement (EEFI) reduced STOD in patients with essential hypertension (EH). We conducted a retrospective cohort analysis of 456 EH patients initially free from STOD. Endothelial function was assessed using brachial artery flow-mediated dilation (FMD), with values ≤ 7.1% indicating dysfunction. Patients were initially categorized by endothelial status (dysfunction: n = 180, normal: n = 276), and further divided into improved or unimproved groups based on changes within three months post-enrollment. During a median follow-up of 25 months, 177 patients developed STOD. The incidence of STOD was significantly higher in patients with initial dysfunction compared to those with normal function. Kaplan–Meier analysis indicated that the improved group had a lower cumulative incidence of STOD compared to the unimproved group (p < 0.05). Multivariable Cox regression confirmed EEFI as an independent protective factor against STOD in EH patients (p < 0.05), regardless of their baseline endothelial status, especially in those under 65 years old, non-smokers, and with low-density lipoprotein cholesterol levels ≤ 3.4 mmol/L. In conclusion, EEFI significantly reduces STOD incidence in EH patients, particularly in specific subgroups, emphasizing the need for early intervention in endothelial function to prevent STOD.
There is currently a lack of a precise, concise, and practical clinical prediction model for predicting coronary artery disease (CAD) in patients with essential hypertension (EH). This study aimed to construct a nomogram to predict CAD in patients with EH based on flow-mediated dilation (FMD) of brachial artery and traditional risk factors. Clinical data of 1752 patients with EH were retrospectively collected. High-resolution vascular ultrasound was used to detect FMD in all patients at the Fujian Hypertension Research Institute, China. Patients were divided into two groups, i.e. training group (n = 1204, from August 2000 to December 2013) and validation group (n = 548, from January 2014 to May 2016) according to the time of enrollment. Independent predictors of CAD were analyzed by multivariable logistic regression in the training group, and a nomogram was constructed accordingly. Finally, we evaluated the discrimination, calibration, and clinical applicability of the model using the area under curve (AUC) of receiver operating characteristic analysis, calibration curve combined with Hosmer-Lemeshow test, and decision curve, respectively. There were 263 (21.8