Changes in source contributions to the oxidative potential of PM2.5 in urban Xiamen, China.

The toxicity of PM2.5 does not necessarily change synchronously with its mass concentration. In this study, the chemical composition (carbonaceous species, water-soluble ions, and metals) and oxidative potential (dithiothreitol assay, DTT) of PM2.5 were investigated in 2017/2018 and 2022 in Xiamen, China. The decrease rate of volume-normalized DTT (DTTv) (38%) was lower than that of PM2.5 (55%) between the two sampling periods. However, the mass-normalized DTT (DTTm) increased by 44%. Clear seasonal patterns with higher levels in winter were found for PM2.5, most chemical constituents and DTTv but not for DTTm. The large decrease in DTT activity (84%-92%) after the addition of EDTA suggested that water-soluble metals were the main contributors to DTT in Xiamen. The increased gap between the reconstructed and measured DTTv and the stronger correlations between the reconstructed/measured DTT ratio and carbonaceous species in 2022 were observed. The decrease rates of the hazard index (32.5%) and lifetime cancer risk (9.1%) differed from those of PM2.5 and DTTv due to their different main contributors. The PMF-MLR model showed that the contributions (nmol/(min·m3)) of vehicle emission, coal + biomass burning, ship emission and secondary aerosol to DTTv in 2022 decreased by 63.0%, 65.2%, 66.5%, and 22.2%, respectively, compared to those in 2017/2018, which was consistent with the emission reduction of vehicle exhaust and coal consumption, the adoption of low-sulfur fuel oil used on board ships and the reduced production of WSOC. However, the contributions of dust + sea salt and industrial emission increased.

Pathways regulating intestinal stem cells and potential therapeutic targets for radiation enteropathy.

Radiotherapy is a pivotal intervention for cancer patients, significantly impacting their treatment outcomes and survival prospects. Nevertheless, in the course of treating those with abdominal, pelvic, or retroperitoneal malignant tumors, the procedure inadvertently exposes adjacent intestinal tissues to radiation, posing risks of radiation-induced enteropathy upon reaching threshold doses. Stem cells within the intestinal crypts, through their controlled proliferation and differentiation, support the critical functions of the intestinal epithelium, ensuring efficient nutrient absorption while upholding its protective barrier properties. Intestinal stem cells (ISCs) regulation is intricately orchestrated by diverse signaling pathways, among which are the WNT, BMP, NOTCH, EGF, Hippo, Hedgehog and NF-κB, each contributing to the complex control of these cells' behavior. Complementing these pathways are additional regulators such as nutrient metabolic states, and the intestinal microbiota, all of which contribute to the fine-tuning of ISCs behavior in the intestinal crypts. It is the harmonious interplay among these signaling cascades and modulating elements that preserves the homeostasis of intestinal epithelial cells (IECs), thereby ensuring the gut's overall health and function. This review delves into the molecular underpinnings of how stem cells respond in the context of radiation enteropathy, aiming to illuminate potential biological targets for therapeutic intervention. Furthermore, we have compiled a summary of several current treatment methodologies. By unraveling these mechanisms and treatment methods, we aspire to furnish a roadmap for the development of novel therapeutics, advancing our capabilities in mitigating radiation-induced intestinal damage.

Non-Islet-Cell Tumor Hypoglycemia Secondary to Malignant Phyllodes Tumor of the Breast.

Background/Objective: Non-islet cell tumor hypoglycemia (NICTH) is an uncommon condition, of which only a few cases caused by malignant phyllodes tumor of the breast have been reported. We describe a case of NICTH secondary to malignant phyllodes tumor with good response to glucocorticoid therapy. Case Report: A 62-year-old woman with a rapidly enlarging left breast mass presented with drowsiness and a capillary blood glucose level of 32.4 mg/dL. Her plasma glucose and insulin levels were 36.0 mg/dL (reference range, 72-144 mg/dL) and 0.6 mIU/L (reference range, 0.0-25.0 mIU/L), respectively. Her beta-hydroxybutyrate and c-peptide levels were undetectable. The insulin-like growth factor (IGF)-I and IGF-II levels were 37 µg/L (reference range, 43-220 µg/L) and 1062 ng/mL (reference range, 333-967 ng/mL), respectively, with an IGF-II:IGF-I molar ratio of 29.4. Prednisolone 30 mg per day was initiated with improvement in hypoglycemia. Outpatient flash glucose monitoring profile was stable with mild hypoglycemia (glucose level, 54-68.5 mg/dL) detected 5% of the time. The patient underwent left mastectomy with axillary clearance 4 weeks later. Histology was reported as malignant phyllodes tumor with extensive ductal carcinoma in situ. Prednisolone was stopped after surgery. The patient was treated with letrozole and adjuvant radiotherapy. There was no recurrence of hypoglycemia during the subsequent 24-month follow-up. Discussion: The mainstay of treatment for NICTH is surgical resection of the culprit tumor. Although glucocorticoid treatment has also been widely used for NICTH, few reports have demonstrated efficacy for NICTH secondary to phyllodes tumor. Conclusion: We report a rare case of malignant phyllodes tumor of the breast resulting in NICTH and demonstrated good response to glucocorticoids as a bridge to definitive surgery.

Silver Telluride Colloidal Quantum Dot Solid for Fast Extended Shortwave Infrared Photodetector.

Extended shortwave infrared (eSWIR) photodetectors that employ solution-processable semiconductors have attracted attention for use in applications such as ranging, night vision, and gas detection. Colloidal quantum dots (CQDs) are promising materials with facile bandgap tunability across the visible-to-mid-infrared wavelengths. However, toxic elements, such as Hg and Pb, and the slow response time of CQD-based IR photodetectors, limit their commercial viability. This article presents a novel eSWIR photodetector that is fabricated using silver telluride (Ag2Te) CQDs. Effective thiolate ligand exchange enables a lower trap density and improved carrier mobility in CQD solids. Furthermore, a vertical p-n photodiode architecture with a favorable energy-level landscape is utilized to facilitate charge extraction, resulting in a fast, room-temperature-operable, and toxic-element-free CQD photodetector. The best eSWIR Ag2Te CQD photodetector exhibits a fall time of 72 ns, representing the fastest response time among all prior CQD-based eSWIR photodetectors, including those containing toxic elements, such as Pb and Hg.

Drug development and evidence for lung cancer targeted therapy in Eastern Asia.

The development of targeted drugs in the Eastern Asia region is going through a flourishing stage. With the continuous advancement of technology and medical research, biotechnology companies and research institutions in the region have made significant progress in cancer field. The Eastern Asian region not only actively participates in clinical trials, but is also committed to developing personalized medical plans to meet the diverse genotypes and phenotypes of patients. The governments and enterprises are increasingly valuing innovation, strengthening international cooperation, and promoting drug development. This paper summarizes the development of genetic testing technology, targeted drugs approval, ongoing promising clinical trials in the field of lung cancer and the important progress made by governments in the Eastern Asian region, and proposed key factors that will contribute to the promising future prospects in the region. The targeted drug market in the Eastern Asian region is expected to drive the medical field forward.

Quantitative changes in platelet count in response to different pathogens: an analysis of patients with sepsis in both retrospective and prospective cohorts.

BACKGROUND: Thrombocytopenia is commonly observed in patients with sepsis and is an independent risk factor for poor prognosis. However, the changes of platelet count caused by different pathogens can vary significantly. Our study aims to evaluate the quantitative changes in platelet count in response to various pathogens. MATERIAL AND METHODS: We retrospectively analysed data of 3044 patients with sepsis from Medical Information Mart for Intensive Care (MIMIC, 2008-2019) database and prospectively collected data of 364 patients with sepsis from our local cohort of the Shandong Bloodstream Infection and Sepsis Collaboration Study (SBISC, 2020-2022). Propensity score matching (PSM) was employed to control for baseline differences in variables, except for the causative pathogen. RESULTS: Multivariate logistic analyses of both original and PSM populations identified Candida, Escherichia, Klebsiella, and Serratia species posing a higher risk for thrombocytopenia compared to others. Restricted cubic spline (RCS) curves showed L- or U-shaped associations between platelet count and 28-mortality with various cut-off values among different pathogens: ranging from 96 × 109/L in Candida species - 190 × 109/L in Klebsiella species. CONCLUSION: Our present findings indicate a pathogen-specific effect on platelet count, highlighting the importance of monitoring thrombocytopenia in patients infected with above microorganisms. Clinicians need to consider pathogen-specific thresholds when intervene on platelet count.

This study validated the differential incidence of thrombocytopenia among various pathogens within two distinct populations.Candida, Escherichia, Klebsiella, and Serratia species were identified as having a notably higher risk of causing thrombocytopenia compared to other pathogens.We observed L- or U-shaped relationships between platelet counts and 28-day mortality in Candida species, Enterococcus species, Escherichia species, Enterobacter species, Staphylococcus species, and Klebsiella species with platelet count cutoff values of 96 × 10⁹/L, 100 × 10⁹/L, 100 × 10⁹/L, 146 × 10⁹/L, 152 × 10⁹/L, and 190 × 10⁹/L, respectively.

The learning curve of a dynamic navigation system used in endodontic apical surgery.

Background/purpose: Quantitative in vitro research was conducted on the learning process of a dynamic navigation system. This study provides guidance for the promotion and application of dynamic navigation technology in the endodontic apical surgery field. Materials and methods: Standardized models were designed and 3D printed to form the approach operation of endodontic apical surgery. 6 clinicians with no experience in dynamic navigation performed the operation. The distance deviation tolerance was set as 0.6 mm, and the angle deviation tolerance was set as 5°. Fifteen mm deep approach operation was completed using dynamic navigation. Each operator performed 10 consecutive exercises on the models. The positioning deviation and operation time of each operator for each practice were recorded. Based on this, the learning curve of the dynamic navigation of every operator was mapped. The learning difficulty of dynamic navigation was evaluated. Results: The learning curves of all operators reached a stable level after the 7th practice, which can ensure that the distance and angle deviations are maintained within the deviation tolerances (0.6 mm, 5°). Conclusion: Operators with no experience in dynamic navigation technology need practice to master dynamic navigation operations. For this navigation system, operators with no operational experience can master dynamic navigation operations after 7 exercises.

Review of Low Titer Group O Whole Blood (LTOWB) Transfusion in Initial Resuscitation of Pediatric Trauma Patients: Assessing Potential Benefits.

BACKGROUND: Hemorrhagic shock secondary to trauma is a leading cause of pediatric mortality in the United States. Timely intervention is crucial to prevent many of these deaths. Children and adults exhibit distinct responses to trauma due to varying blood volume ratios and injury patterns. Pediatric patients with hypotension face a heightened risk of shock, demanding a more assertive resuscitation. METHODS: This study is a review of the literature on LTOWB transfusion in pediatric trauma. We conducted electronic database searches until December 2022, using keywords related to LTOWB and pediatric trauma resuscitation. Randomized/non-randomized, retrospective/prospective studies were considered, assessing serological safety, adverse reactions, clinical outcomes, and cost-effectiveness. RESULTS: Six articles were ultimately reviewed. No adverse reactions related to hemolysis biomarkers were observed. Clinical outcomes exhibited no significant differences in mortality, hospital, or ventilator days between LTOWB and component therapy (CT). However, LTOWB transfusion resulted in faster resolution of base deficit, lower INR, and reduced requirement for additive plasma and platelet transfusions. In military and massive transfusion cases, LTOWB was associated with decreased mortality and lower transfusion volumes. One article suggested potential economic advantages. CONCLUSIONS: LTOWB transfusion appears to be a promising option for pediatric trauma resuscitation, offering benefits in rapid administration and component balance. While some studies indicate potential advantages in clinical outcomes and cost-effectiveness, the current evidence is limited and requires further investigation. Future research should focus on large-scale studies to validate these findings, especially concerning economic benefits, and develop standardized protocols for LTOWB use in pediatric settings. LEVELS OF EVIDENCE: Treatment Study, LEVEL III.

Strategies, techniques and applications for food authentication based on carbohydrates: A review.

The increasing complexity and ubiquity of food processing and the emergence of fraudulent practices have made effective and reliable methods to authenticate food products of utmost importance. Carbohydrates, with various nutritional functions, are abundant in foods and can serve as potential markers for food authentication. However, the complex and diverse structures and properties of carbohydrates, especially polysaccharides, pose challenges. Nonetheless, significant progress has been made in this area. This paper provides an overview of the utilization of carbohydrates in food authentication since 2000, focusing on strategies involving carbohydrate-based markers, carbohydrate profiles, and carbohydrate-protein interaction-based assays. The analytical techniques, applications, challenges and limitations of these strategies are reviewed and discussed. The findings demonstrate that these strategies offer origin verification, quality assessment, adulteration detection, process control, and food species identification. Notably, oligosaccharide analysis has proven effective in food authentication and remains a promising marker, especially for analyzing intricate matrices. The advances in chromatography separation and mass spectrometry identification of isomers and trace amounts of these compounds have facilitated the discovery of such markers. In conclusion, carbohydrate analysis can play a crucial role in food authentication. Future research and development will make the authentication of carbohydrate-rich foods ever more accurate and efficient.

Opportunistic Assessment of Hip Fracture Risk Based on Chest CT.

OBJECTIVE: Hip fracture (HF) has been described as the "last fracture of life" in the elderly, so the assessment of HF risk is extremely important. Currently, few studies have examined the relationship between imaging data from chest computed tomography (CT) and HF. This study demonstrated that pectoral muscle index (PMI) and vertebral body attenuation values could predict HF, aiming to opportunistically assess the risk of HF in patients without bone mineral density (BMD) based on chest CT for other diseases. METHODS: In the retrospective study, 800 participants who had both BMD and chest CT were enrolled from January 2021 to January 2024. After exclusion, 472 patients were finally enrolled, divided into the healthy control (HC) group and the HF group. Clinical data were collected, and differences between the two groups were compared. A predictive model was constructed based on the PMI and CT value of the fourth thoracic vertebra (T4HU) by logistic regression analysis, and the predictive effect of the model was analyzed by using the receiver operating characteristic (ROC) curve. Finally, the clinical utility of the model was analyzed using decision curve analysis (DCA) and clinical impact curves. RESULTS: Both PMI and T4HU were lower in the HF group than in the HC group (p < 0.05); low PMI and low T4HU were risk factors for HF. The predictive model incorporating PMI and T4HU on the basis of age and BMI had excellent diagnostic efficacy with an area under the curve (AUC) of 0.865 (95% confidence interval [CI]: 0.830-0.894, p < 0.01), sensitivity and specificity of 0.820 and 0.754, respectively. The clinical utility of the model was validated using calibration curves and DCA. The AUC of the predictive model incorporating BMD based on age and BMI was 0.865 (95% CI: 0.831-0.895, p < 0.01), with sensitivity and specificity of 0.698 and 0.711, respectively. There was no significant difference in diagnostic efficacy between the two models (p = 0.967). CONCLUSIONS: PMI and T4HU are predictors of HF in patients. In the absence of dual-energy x-ray absorptiometry (DXA), the risk of HF can be assessed by measuring the PMI and T4HU on chest CT examination due to other diseases, and further treatment can be provided in time to reduce the incidence of HF.

Ultrasomics differentiation of malignant and benign focal liver lesions based on contrast-enhanced ultrasound.

OBJECTIVES: To establish a nomogram for differentiating malignant and benign focal liver lesions (FLLs) using ultrasomics features derived from contrast-enhanced ultrasound (CEUS). METHODS: 527 patients were retrospectively enrolled. On the training cohort, ultrasomics features were extracted from CEUS and b-mode ultrasound (BUS). Automatic feature selection and model development were performed using the Ultrasomics-Platform software, outputting the corresponding ultrasomics scores. A nomogram based on the ultrasomics scores from artery phase (AP), portal venous phase (PVP) and delayed phase (DP) of CEUS, and clinical factors were established. On the validation cohort, the diagnostic performance of the nomogram was assessed and compared with seniorexpert and resident radiologists. RESULTS: In the training cohort, the AP, PVP and DP scores exhibited better differential performance than BUS score, with area under the curve (AUC) of 84.1-85.1% compared with the BUS (74.6%, P < 0.05). In the validation cohort, the AUC of combined nomogram and expert was significantly higher than that of the resident (91.4% vs. 89.5% vs. 79.3%, P < 0.05). The combined nomogram had a comparable sensitivity with the expert and resident (95.2% vs. 98.4% vs. 97.6%), while the expert had a higher specificity than the nomogram and the resident (80.6% vs. 72.2% vs. 61.1%, P = 0.205). CONCLUSIONS: A CEUS ultrasomics based nomogram had an expert level performance in FLL characterization.

The different effects of four adenosine receptors in liver fibrosis.

Background: The adenosine-adenosine receptor pathway plays important roles in the immune system and inflammation. Four adenosine receptors (i.e., A1R, A2AR, A2BR, and A3R) have been identified. However, the roles of these receptors were different in the disease progress and even play opposite roles in the same disease. This study aims to investigate the roles of A1R/A2AR/A2BR/A3R activation in liver fibrosis. Methods: Intraperitoneal injection of CCl4 into C57BL/6 mice was used to induce liver fibrosis in the models. Adenosine receptor agonists CCPA, CGS21680, BAY 60-6583, and namodenoson were used for A1R/A2AR/A2BR/A3R activation, respectively. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were used to evaluate the liver function. Hematoxylin and eosin (H&E) staining was used to investigate the pathological damage. Masson staining and Sirius Red staining were performed to evaluate the degree of collagen deposition. CCK8 and scratch assays were used to investigate the proliferation and migration ability of hepatic stellate cells (HSCs). Results: By using liver fibrosis mouse models, we observed that the A1R and A2AR agonists aggravated liver fibrosis, characterized by increasing ALT and AST levels, more serious liver pathological damage, and collagen deposition. However, the A2BR and A3R agonists alleviated liver fibrosis. Moreover, the A1R and A2AR agonist treatment promotes the proliferation and migration of HSC line LX2, while A2BR and A3R agonist treatment inhibited LX2 proliferation and migration. Consistently, A1R and A2AR agonist treatment elevated the expression of α-SMA and Col1α1 in LX2, whereas A2BR and A3R agonist treatment inhibited the expression of α-SMA and Col1α1 in LX2 cells. Additionally, 5'-N-ethyl-carboxamidoadenosine (NECA), a metabolically stable adenosine analog, alleviated liver fibrosis and inhibited LX2 cell activity, proliferation, and migration. Conclusion: This study demonstrated the different roles of A1R/A2AR/A2BR/A3R during liver fibrosis development via regulating the HSC activity and proliferation.

Corrigendum: Knowledge and thresholds for palliative care and surgery among healthcare providers caring for adults with serious illness.

[This corrects the article DOI: 10.3389/fmed.2024.1351864.].

Huang-Lian-Jie-Du Decoction alleviates diabetic encephalopathy by regulating inflammation and pyroptosis via suppression of AGEs/RAGE/NF-κB pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Cognitive dysfunction associated with diabetes, known as diabetic encephalopathy (DE), is a grave neurodegenerative condition triggered by diabetes, and persistent inflammation plays a vital role in its development. The renowned traditional Chinese medicine Huang-Lian-Jie-Du Decoction (HLJDD) is clinically proven to manage diabetes mellitus and Alzheimer's disease and is famous for its heat-clearing and detoxifying effects. However, the underlying mechanisms through which HLJDD affects DE remain to be elucidated. AIM OF THE STUDY: To explore the beneficial effects of HLJDD on improving cognitive dysfunction in DE mice. STUDY DESIGN AND METHODS: A diabetic mouse was established through a high-fat diet and subsequent administration of streptozotocin over five consecutive days. After the animals were confirmed to have diabetes, they were treated with HLJDD. After oral administration of HLJDD or metformin for 14 weeks, behavioral tests were used to assess their cognitive capacity. Biochemical analyses were then performed to detect levels of glucose metabolism, followed by histological analyses to assess pathological damage. Furthermore, AGEs/RAGE/NF-κB axis related proteins were detected by Western blot or immunofluorescence techniques. An advanced UPLC-Q-Orbitrap HRMS/MS analytical technique utilizing a chemical derivatization strategy was employed for comprehensive metabolic profiling of carbonyl compounds in the plasma of DE mice. RESULTS: Pharmacological assessment revealed that HLJDD effectively mitigated cognitive dysfunction, normalized glucose metabolic imbalances, and repaired neuronal damage in DE mice. It reduced neuroinflammation by attenuating carbonyl stress, deactivating astrocytes and microglia, and preserving dopaminergic neurons. Additionally, metabolomics analysis revealed 18 carbonyl compounds with marked disparities between DE and control mice, with 12 metabolites approaching normal levels post-HLJDD intervention. Further investigations showed that HLJDD regulated inflammation and pyroptosis through suppressing AGEs/RAGE/NF-κB pathways. CONCLUSION: Our study indicated that HLJDD could ameliorate carbonyl stress via the regulation of carbonyl compound metabolism profiling, and inhibiting the AGEs/RAGE/NF-κB pathway, thereby alleviating inflammation and pyroptosis to exert beneficial effects on DE.

Protein phosphatase 4 maintains the survival of primordial follicles by regulating autophagy in oocytes.

In mammalian ovary, the primordial follicle pool serves as the source of developing follicles and fertilizable ova. To maintain the normal length of female reproductive life, the primordial follicles must have adequate number and be kept in a quiescent state before menopause. However, the molecular mechanisms underlying primordial follicle survival are poorly understood. Here, we provide genetic evidence showing that lacking protein phosphatase 4 (PPP4) in oocytes, a member of PP2A-like subfamily, results in infertility in female mice. A large quantity of primordial follicles has been depleted around the primordial follicle pool formation phase and the ovarian reserve is exhausted at about 7 months old. Further investigation demonstrates that depletion of PPP4 causes the abnormal activation of mTOR, which suppresses autophagy in primordial follicle oocytes. The abnormal primordial follicle oocytes are eventually erased by pregranulosa cells in the manner of lysosome invading. These results show that autophagy prevents primordial follicles over loss and PPP4-mTOR pathway governs autophagy during the primordial follicle formation and dormant period.

Association between PER and CRY gene polymorphisms and the response to caffeine citrate treatment in infants with apnea of prematurity.

Background: Circadian rhythms impact metabolism and the therapeutic effects of drugs. The purpose of this study was to determine the association between PER and CRY polymorphisms and caffeine citrate treatment response in infants with apnea of prematurity. Methods: A total of 221 preterm infants of gestational age <34 weeks were included in this study (160 in the response group and 61 in the non-response group). The propensity score matching method was used to perform a 1:1 matching for all premature infants, and the general characteristics and clinical outcomes of the two groups were compared. The association between polymorphisms of the circadian transcription repressors PER and CRY and caffeine citrate treatment response in infants with apnea of prematurity was analyzed with co-dominant, dominant, recessive, and over-dominant models, as well as analysis of alleles. Generalized multifactor dimensionality reduction (GMDR) analysis was used to analyze the interaction between the PER and CRY genes. Results: After propensity score matching, 45 preterm infants were included in each of the response and non-response groups, and there were no statistically significant differences in general characteristics between the two groups (P > 0.05). Infants in the non-response groups had a higher incidence of moderate and severe bronchopulmonary dysplasia (BPD) (P = 0.043), retinopathy of prematurity (ROP) (P = 0.035), and invasive ventilation (P = 0.027), and their duration of oxygen use (P = 0.041) was longer. When corrected for false discovery rate, the PER3 rs228669 recessive model (P FDR = 0.045) and the over-dominant model (P FDR = 0.045) were both associated with caffeine citrate treatment response. Preterm infants with the rs228669 CC genotype had a significantly lower rate of caffeine citrate non-response in the recessive model (OR = 0.28, 95% CI = 0.12-0.66), which was significantly higher in preterm infants with the CT genotype in the over-dominant model (OR = 4.18, 95% CI = 1.64-10.66). GMDR analysis revealed an interaction between the PER and CRY genes (P < 0.05). Conclusions: Circadian rhythms may play a role in the response of premature infants to caffeine citrate, and polymorphisms of the PER and CRY genes may influence the effectiveness of caffeine citrate treatment for apnea of prematurity.

A real-world study on the treatment of extremely preterm infants: a multi-center study in southwest area of Fujian Province in China.

BACKGROUND: Due to regional and cultural differences, the current status of extremely preterm infants(EPIs) treatment across different areas of mainland China remains unclear. This study investigated the survival rate and incidence of major diseases among EPIs in the southwest area of Fujian province. METHOD: This retrospective and multicenter study collected perinatal data from EPIs with gestational ages between 22-27+ 6w and born in the southwest area of Fujian province. The study population was divided into 6 groups based on gestational age at delivery. The primary outcome was the survival status at ordered hospital discharge or correct gestational age of 40 weeks, and the secondary outcome was the incidence of major diseases. The study analyzed the actual survival status of EPIs in the area. RESULT: A total of 2004 preterm infants with gestational ages of 22-27+ 6 weeks were enrolled in this study. Among them, 1535 cases (76.6%) were born in the delivery room but did not survive, 469 cases (23.4%) were transferred to the neonatal department for treatment, 101 cases (5.0%) received partial treatment, and 368 cases (18.4%) received complete treatment. The overall all-cause mortality rate was 84.4% (1691/2004). The survival rate and survival rate without major serious disease for EPIs who received complete treatment were 85.1% (313/368) and 31.5% (116/318), respectively. The survival rates for gestational ages 22-22+ 6w, 23-23+ 6w, 24-24+ 6w, 25-25+ 6w, 26-26+ 6w, and 27-27+ 6w were 0%, 0%, 59.1% (13/22), 83% (39/47), 88.8% (87/98), and 89.7% (174/198), respectively. The survival rates without major serious disease were 0%, 0%, 9.1% (2/22), 19.1% (9/47), 27.6% (27/98), and 40.2% (78/194), respectively. CONCLUSION: The all-cause mortality of EPIs in the southwest area of Fujian Province remains high, with a significant number of infants were given up after birth in the delivery room being the main influencing factor. The survival rate of EPIs who received complete treatment at 25-27 weeks in the NICU was similar to that in developed countries. However, the survival rate without major serious disease was significantly lower compared to high-income countries.

Przewaquinone A inhibits Angiotensin II-induced endothelial diastolic dysfunction activation of AMPK.

BACKGROUND: Endothelial dysfunction (ED), characterized by markedly reduced nitric oxide (NO) bioavailability, vasoconstriction, and a shift toward a proinflammatory and prothrombotic state, is an important contributor to hypertension, atherosclerosis, and other cardiovascular diseases. Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) is widely involved in cardiovascular development. Przewaquinone A (PA), a lipophilic diterpene quinone extracted from Salvia przewalskii Maxim, inhibits vascular contraction. PURPOSE: Herein, the goal was to explore the protective effect of PA on ED in vivo and in vitro, as well as the underlying mechanisms. METHODS: A human umbilical vein endothelial cell (HUVEC) model of ED induced by angiotensin II (AngII) was used for in vitro observations. Levels of AMPK, endothelial nitric oxide synthase (eNOS), vascular cell adhesion molecule-1 (VCAM-1), nitric oxide (NO), and endothelin-1 (ET-1) were detected by western blotting and ELISA. A mouse model of hypertension was established by continuous infusion of AngII (1000 ng/kg/min) for 4 weeks using osmotic pumps. Following PA and/or valsartan administration, NO and ET-1 levels were measured. The levels of AMPK signaling-related proteins in the thoracic aorta were evaluated by immunohistochemistry. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) were measured using the tail cuff method. Isolated aortic vascular tone measurements were used to evaluate the vasodilatory function in mice. Molecular docking, molecular dynamics, and surface plasmon resonance imaging (SPRi) were used to confirm AMPK and PA interactions. RESULTS: PA inhibited AngII-induced vasoconstriction and vascular adhesion as well as activated AMPK signaling in a dose-dependent manner. Moreover, PA markedly suppressed blood pressure, activated vasodilation in mice following AngII stimulation, and promoted the activation of AMPK signaling. Furthermore, molecular simulations and SPRi revealed that PA directly targeted AMPK. AMPK inhibition partly abolished the protective effects of PA against endothelial dysfunction. CONCLUSION: PA activates AMPK and ameliorates endothelial dysfunction during hypertension.

Paeoniflorin suppresses ferroptosis after traumatic brain injury by antagonizing P53 acetylation.

BACKGROUND: Traumatic brain injury (TBI) could induce multiple forms of cell death, ferroptosis, a novel form of cell death distinct from apoptosis and autophagy, plays an important role in disease progression in TBI. Therapies targeting ferroptosis are beneficial for recovery from TBI. Paeoniflorin (Pae) is a water-soluble monoterpene glycoside and the active ingredient of Paeonia lactiflora pall. It has been shown to exert anti-inflammatory and antioxidant effects. However The effects and mechanisms of paeoniflorin on secondary injury after TBI are unknown. PURPOSE: To investigate the mechanism by which Pae regulates ferroptosis after TBI. METHODS: The TBI mouse model and cortical primary neurons were utilized to study the protective effect of paeoniflorin on the brain tissue after TBI. The neuronal cell ferroptosis model was established by treating cortical primary neurons with erastin. Liproxstatin-1(Lip-1) was used as a positive control drug. Immunofluorescence staining, Nissl staining, biochemical analyses, pharmacological analyses, and western blot were used to evaluate the effects of paeoniflorin on TBI. RESULTS: Pae significantly ameliorated neuronal damage after TBI, inhibited mitochondrial damage, increased glutathione peroxidase 4 (GPX4) activity, decreased malondialdehyde (MDA) production, restored neurological function and inhibited cerebral edema. Pae promotes the degradation of P53 in the form of proteasome, promotes its ubiquitination, and reduces the stability of P53 by inhibiting its acetylation, thus alleviating the P53-mediated inhibition of cystine/glutamate antiporter solute carrier family 7 member 11 (SLC7A11) by P53. CONCLUSION: Pae inhibits ferroptosis by promoting P53 ubiquitination out of the nucleus, inhibiting P53 acetylation, and modulating the SLC7A11-GPX4 pathway.

Bispillar[5]arene-Based Slide-Ring Polyrotaxanation Enables Enhanced Toughness, Recyclability, Impact, and Puncture Resistance of Polyisoprene Elastomers.

A series of slide-ring polyrotaxanes (SRPs) have been constructed by the solvent-free blending of a ditopic pillar[5]arene (DP5A) and polyisoprene (PIP) after thermal annealing. Solid-state 13C NMR experiments supported the fact that the pillar[5]arene rings of DP5A were threaded by PIP chains to afford physically interlocked networks. Tensile tests revealed that 1% of DP5A can improve the elongation at break from 50 to 239%, the tensile modulus from 2.1 to 3.9 MPa, and the toughness from 0.35 to 4.5 MJ/m3. Impact and puncture resistance experiments show that the DP5A-doped materials exhibit remarkable enhancement of protective and impalement-resistant performance. The samples can be also recycled repeatedly due to their physical crosslinking nature. The important stress delocalization effects have been attributed to the pulley effect of DP5A in the SRP materials, which represents a supramolecular approach for improving the performance of PIP elastomers.