The angle of the lower portion of the posterior cruciate ligament assists in the diagnosis of partial anterior cruciate ligament tears.

PURPOSE: To compare the difference of angle of the lower portion of the posterior cruciate ligament (PCL) measured via magnetic resonance imaging (MRI) in patients with and without partial anterior cruciate ligament (ACL) tears and to investigate the effectiveness of the angle of the lower portion of the PCL in diagnosing partial ACL tears. METHODS: From January 2022 to December 2022, a cohort of consecutive patients presenting with ACL tears who underwent ACL reconstruction and patients with isolated meniscus tears undergoing arthroscopic surgery were enroled for this study. The angle of the inferior portion of the PCL comprises α and ß angles, and the posterior offset of the lateral condyle were measured on the MRI and compared between the partial ACL tear and control groups. Receiver operating characteristic curves, the areas under the curve (AUCs) and the 95% confidence intervals (CIs) were calculated to identify cutoff values for diagnosing partial ACL injuries. RESULTS: Following an assessment of cohort eligibility and matching for age and sex, 100 patients were included in this study. The mean age of the cohort was 46.1 ± 10.3 years. The AUC for the α angle was 0.88 (95% CI, 0.82-0.94), with a sensitivity of 0.74 and specificity of 0.84 for predicting partial ACL ruptures; the α angle cutoff value was 73.6° (diagnostic odds ratio (OR), 14.10; 95% CI, 5.33-37.28). The AUC for the ß angle was 0.86 (95% CI, 0.79-0.93), with a sensitivity of 0.64 and a specificity of 0.92 for predicting partial ACL ruptures; the ß angle cutoff value was 73.3° (diagnostic OR, 14.54; 95% CI, 5.76-36.68). CONCLUSIONS: A small α angle and a large ß angle were associated with partial ACL tears. The angle of the distal portion of the PCL was simple to measure and reproducible, enhancing the diagnosis of partial ACL tears. LEVEL OF EVIDENCE: Level III.

Low skeletal muscle mass is associated with inferior preoperative and postoperative shoulder function in elderly rotator cuff tear patients.

BACKGROUND: The age-related loss of skeletal muscle mass is an important characteristic of sarcopenia, an increasingly recognized condition with systemic implications. However, its association with shoulder function in elderly patients with rotator cuff tears (RCT) remains unknown. This study aimed to investigate the relationship between low skeletal muscle mass and shoulder function in elderly RCT patients. METHODS: A retrospective analysis was conducted on RCT patients who underwent chest computed tomography (CT) scans for clinical evaluation. Preoperative CT scan images of the chest were used to calculate the cross-sectional area (CSA) of thoracic muscle at the T4 level. The medical records were reviewed. Shoulder function was assessed using the ASES score and CMS score both preoperatively and at the final follow-up. Data on the preoperative range of motion (ROM) for the affected shoulder, were collected for analysis. Subgroup analyses by sex were also performed. RESULTS: A total of 283 RCT patients, consisting of 95 males and 188 females, with a mean age of 66.22 ± 4.89(range, 60-95 years) years were included in this retrospective study. The low muscle mass group showed significantly higher level of c-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) compared to the normal group(3.75 ± 6.64 mg/L vs. 2.17 ± 2.30 mg/L, p = 0.021; 19.08 ± 12.86 mm/H vs.15.95 ± 10.76 mm/H, p = 0.038; respectively). In the normal group, pre-operative passive ROM, including forward elevation, abduction, lateral rotation, and abductive external rotation, was significantly better than that in the low muscle mass group (127.18 ± 34.87° vs. 89.76 ± 50.61°; 119.83 ± 45.76° vs. 87.16 ± 53.32°; 37.96 ± 28.33° vs. 25.82 ± 27.82°; 47.71 ± 23.56° vs. 30.87 ± 27.76°, all p < 0.01, respectively). Similar results were found in the active ROM of the shoulder. The female low muscle mass group exhibited significantly poorer passive and active ROM (p < 0.05). The post-operative ASES scores and CMS scores of the female low muscle mass group were also statistically worse than those of the female normal group (p < 0.05). CONCLUSIONS: The results of present study revealed that the low skeletal muscle mass is associated with inferior ROM of the shoulder and per- and post-operative shoulder function, especially for elderly female patients.

Nucleolin myocardial-specific knockout exacerbates glucose metabolism disorder in endotoxemia-induced myocardial injury.

Background: Sepsis-induced myocardial injury, as one of the important complications of sepsis, can significantly increase the mortality of septic patients. Our previous study found that nucleolin affected mitochondrial function in energy synthesis and had a protective effect on septic cardiomyopathy in mice. During sepsis, glucose metabolism disorders aggravated myocardial injury and had a negative effect on septic patients. Objectives: We investigated whether nucleolin could regulate glucose metabolism during endotoxemia-induced myocardial injury. Methods: The study tested whether the nucleolin cardiac-specific knockout in the mice could affect glucose metabolism through untargeted metabolomics, and the results of metabolomics were verified experimentally in H9C2 cells. The ATP content, lactate production, and oxygen consumption rate (OCR) were evaluated. Results: The metabolomics results suggested that glycolytic products were increased in endotoxemia-induced myocardial injury, and that nucleolin myocardial-specific knockout altered oxidative phosphorylation-related pathways. The experiment data showed that TNF-α combined with LPS stimulation could increase the lactate content and the OCR values by about 25%, and decrease the ATP content by about 25%. However, interference with nucleolin expression could further decrease ATP content and OCR values by about 10-20% and partially increase the lactate level in the presence of TNF-α and LPS. However, nucleolin overexpression had the opposite protective effect, which partially reversed the decrease in ATP content and the increase in lactate level. Conclusion: Down-regulation of nucleolin can exacerbate glucose metabolism disorders in endotoxemia-induced myocardial injury. Improving glucose metabolism by regulating nucleolin was expected to provide new therapeutic ideas for patients with septic cardiomyopathy.

Energy Metabolism: From Physiological Changes to Targets in Sepsis-induced Cardiomyopathy.

Sepsis is a systemic inflammatory response syndrome caused by a variety of dysregulated responses to host infection with life-threatening multi-organ dysfunction. Among the injuries or dysfunctions involved in the course of sepsis, cardiac injury and dysfunction often occur and are associated with the pathogenesis of hemodynamic disturbances, also defined as sepsis-induced cardiomyopathy (SIC). The process of myocardial metabolism is tightly regulated and adapts to various cardiac output demands. The heart is a metabolically flexible organ capable of utilizing all classes of energy substrates, including carbohydrates, lipids, amino acids, and ketone bodies to produce ATP. The demand of cardiac cells for energy metabolism changes substantially in septic cardiomyopathy with distinct etiological causes and different times. This review describes changes in cardiomyocyte energy metabolism under normal physiological conditions and some features of myocardial energy metabolism in septic cardiomyopathy, and briefly outlines the role of the mitochondria as a center of energy metabolism in the septic myocardium, revealing that changes in energy metabolism can serve as a potential future therapy for infectious cardiomyopathy.

Bicomponent core/sheath melt-blown fibers for air filtration with ultra-low resistance.

With the escalating air pollution and frequent outbreaks of airborne diseases, there is a growing demand for personal protective filtration media. Melt-blown nonwovens have proven to be highly effective in capturing tiny particles, but their tightly packed fiber assemblages are more resistant to airflow and less comfortable to breathe. Here, we present a one-step melt-blown spinning process for the production of bicomponent core/sheath (BCS) crimped fibers and their application in high-efficiency, low-resistance air filtration. Fiber curl is caused by unbalanced internal stresses resulting from differences in the structure components, resulting in uneven shrinkage inside and outside the fibers. The resulting CM@S-2 filtration media features a uniform fiber curl and a porous fiber mesh structure, which reduces air filtration resistance. Under the same filtration conditions, the filtration efficiency of CM@S-2 (96.58% vs. 95.58%), filtration resistance (56.1 Pa vs. 108.0 Pa), quality factor (0.061 Pa-1vs. 0.029 Pa-1), and dust holding capacity (10.60 g m-2vs. 9.10 g m-2) were comparable to those of the single-component polypropylene filters. The filtration efficiency of the CM@S-2 remained above 94.0% after 30 days of indoor storage. Computational Fluid Dynamics (CFD) simulation demonstrated that crimped fibers effectively reduce pressure surges on the filter media caused by fiber accumulation. In comparative tests with commercial masks, the CM@S-2 cartridge masks demonstrated superior air permeability compared to commercial masks under similar filtration conditions. In conclusion, the bicomponent core/sheath melt-blown fibers significantly reduce air resistance and show excellent potential for application in protective masks.

Reduced representative methylome profiling of cell-free DNA for breast cancer detection.

BACKGROUND: Whole-genome methylation sequencing of cfDNA is not cost-effective for tumor detection. Here, we introduce reduced representative methylome profiling (RRMP), which employs restriction enzyme for depletion of AT-rich sequence to achieve enrichment and deep sequencing of CG-rich sequences. METHODS: We first verified the ability of RRMP to enrich CG-rich sequences using tumor cell genomic DNA and analyzed differential methylation regions between tumor cells and normal whole blood cells. We then analyzed cfDNA from 29 breast cancer patients and 27 non-breast cancer individuals to detect breast cancer by building machine learning models. RESULTS: RRMP captured 81.9% CpG islands and 75.2% gene promoters when sequenced to 10 billion base pairs, with an enrichment efficiency being comparable to RRBS. RRMP allowed us to assess DNA methylation changes between tumor cells and whole blood cells. Applying our approach to cfDNA from 29 breast cancer patients and 27 non-breast cancer individuals, we developed machine learning models that could discriminate between breast cancer and non-breast cancer controls (AUC = 0.85), suggesting possibilities for truly non-invasive cancer detection. CONCLUSIONS: We developed a new method to achieve reduced representative methylome profiling of cell-free DNA for tumor detection.

Effectiveness of bone grafting versus cannulated screw fixation in the treatment of posterolateral tibial plateau compression fractures with concomitant ACL injury: a comparative study.

BACKGROUND: Posterolateral tibial plateau compression fractures (PTPCF) are one of the significant factors leading to knee instability and anterior cruciate ligament (ACL) reconstruction failure. The effectiveness of fixation for such cases without the use of metal implants remains inconclusive. The aim of this study is to investigate whether the fixation with isolated bone grafting is stable enough for the treatment of PTPCF with concomitant ACL injuries. METHODS: This retrospective study analyzed patients treated for concomitant ACL injuries and PTPCF in authors' institution. A total of 53 patients (21 males and 32 females) with an average age of 47.43 ± 14.71 years were included. Patient data were collected, including factors leading to injury, affected side, height, weight, and basic medical history. The posterior inclination angle and the lateral tibial plateau lateral inclination angle were measured to evaluate the fixation stability. Rasmussen functional score and HSS score were used to assess the knee functional recovery. RESULTS: The bone grafting group achieved satisfactory levels of Rasmussen score (28.22 ± 0.85) and HSS knee joint function scores (95.57 ± 1.97). The cannulated screw fixation group had a Rasmussen knee joint function score of 28.70 ± 0.92 and a HSS knee joint function score of 96.07 ± 1.93. No statistically significant difference was found (P > 0.05). The cannulated screw fixation group had a mean posterior inclination angle reduction loss of 0.20° ± 1.11°, while the bone grafting group had a reduction loss of 0.18° ± 1.01°, with no statistically significant difference (P > 0.05). The cannulated screw fixation group had a lateral inclination angle reduction loss of 0.01° ± 0.37°, and the bone grafting group had a reduction loss of 0.03° ± 0.43°, with no statistically significant difference (P > 0.05). CONCLUSION: The use of bone grafting for fixation of PTPCF with accompanying ACL injuries demonstrated no substantial disparities in knee joint function. In cases of simple PTPCF, filling and compacting the bone defect underneath the tibial plateau fracture fragment can yield satisfactory fixation, obviating the necessity for supplementary cannulate screw fixation.

Mesenchymal stem cell-derived exosomes in myocardial infarction: Therapeutic potential and application.

Myocardial infarction refers to the irreversible impairment of cardiac function resulting from the permanent loss of numerous cardiomyocytes and the formation of scar tissue. This condition is caused by acute and persistent inadequate blood supply to the heart's arteries. In the treatment of myocardial infarction, Mesenchymal stem cells (MSCs) play a crucial role because of their powerful therapeutic effects. These effects primarily stem from the paracrine secretion of multiple factors by MSCs, with exosome-carried microRNAs being the most effective component in promoting cardiac function recovery after infarction. Exosome therapy has emerged as a promising cell-free treatment for myocardial infarction as a result of its relatively simple composition, low immunogenicity and controlled transplantation dose. Despite these advantages, maintaining the stability of exosomes after transplantation and enhancing their targeting effect remain significant challenges in clinical applications. In recent developments, several approaches have been designed to optimize exosome therapy. These include enhancing exosome retention, improving their ability to target specific effects, pretreating MSC-derived exosomes and employing transgenic MSC-derived exosomes. This review primarily focuses on describing the biological characteristics of exosomes, their therapeutic potential and their application in treating myocardial infarction.

Postmarketing Safety of Sacituzumab Govitecan: A Pharmacovigilance Study Based on the FDA Adverse Event Reporting System.

Sacituzumab govitecan is widely used for the treatment of breast cancer and urothelial carcinoma, but available information regarding adverse events (AEs) is limited. We aim to explore the AE induced by sacituzumab govitecan by mining the FDA Adverse Event Reporting System (FAERS) database. The association between sacituzumab govitecan and AEs was evaluated using the information component. A multivariate logistic regression analysis was conducted for all identified signals to explore the risk factors associated with AEs leading to hospitalization. In total, 1,884 reports related to sacituzumab govitecan were retrieved, and 114 AE signals involving 20 systems were identified. The median time for onset of AEs was ~ 6-7 days after initiating treatment with sacituzumab govitecan, with over 80% of AEs occurring within 30 days. Subgroup analysis revealed that 14 signals were reported in men and 110 in women. There were 58 signals reported in patients under 65 following the use of sacituzumab govitecan, 59 signals in patients over 65, and 31 signals were present in both groups. Multivariable analysis showed that being male and the occurrence of colitis, pneumonitis, febrile neutropenia, pyrexia, sepsis, dehydration, and diarrhea were risk factors leading to hospitalization with an area under the curve (AUC) of 0.89. Additionally, sensitivity analysis revealed that this study had good robustness. This is the first retrospective analysis based on FAERS to review the safety of sacituzumab govitecan. The results highlight the need to closely monitor adverse reactions such as neutropenia, diarrhea, colitis, and sepsis when using sacituzumab govitecan.

Risk factors for drug-related acute pancreatitis: an analysis of the FDA adverse event reporting system (FAERS).

Objective: While several drugs have been linked to acute pancreatitis (AP), the AP-related risk of most drugs remains unclear. This study investigated the risk factors for drug-induced AP by analyzing a large dataset from the FDA Adverse Event Reporting System (FAERS). Methods: The reporting odds ratios (ROR) were used to assess the reports of drug-induced AP from the first quarter of 2004 to the second quarter of 2022. Single-factor, LASSO, and multi-factor regression analysis were performed to explore drug-related AP-related risk factors. Bonferroni correction was applied for the multiple comparisons performed. Results: A total of 264 drugs associated with AP, including antineoplastic drugs (35/264), antidiabetic drugs (28/264), antibacterial drugs (24/264), immunomodulatory drugs (11/264), antipsychotic drugs (6/264), and other drugs (160/264) were retrieved. Multi-factor analysis showed that males, age 41-54 years old, and 36 drugs, including Tigecycline, were risk factors for drug-related AP. The median time to drug-related AP onset was 31 days (interquartile range [IQR] 7-102 days) and about 75% of adverse events occurred within 100 days. Conclusion: These findings may help clinicians to identify drug-related AP at the early stage and can be used to inform future studies of drug-related AP pathogenesis.

Preparation of Self-Curling Melt-Blown Fibers with Crimped Masterbatch (CM) and Its Application for Low-Pressure Air Filtration.

Particulate matter (PM) and airborne viruses pose significant threats to both the environment and public health. As the most viable solution to prevent the inhalation of these pollutants, there is an urgent demand for face masks with excellent filtration efficiency and low-pressure drop. In this study, a crimped masterbatch (CM) is added to polypropylene feedstocks to produce curling fibers through melt-blown spinning. These curled fibers exhibit low filtration resistance and effective dust-holding performances when used for air filtration. The effect of adding CM on fiber diameter, pore size, crimp, porosity, roughness, and surface potential was studied. The filtration performance of the materials, including the PM filtration capabilities, recirculation filtration, and loading test performance, were also investigated. The results demonstrate that the degree of fiber crimp can be adjusted by incorporating varying amounts of CM. This curling was caused by the uneven shrinkage that occurred due to variations in thermal contraction between these polymers. The curled fibers created a fluffy structure in the fiber network and modified the distribution of pore sizes within it. Under the same filtration conditions as sodium chloride aerogel, CM-2 (PP:CM 8:2) exhibited similar filtration efficiency (95.54% vs. 94.74%), lower filtration resistance (88.68 Pa vs. 108.88 Pa), higher quality factor (0.035 Pa-1 vs. 0.028 Pa-1) and better dust holding capacity (10.39 g/m2 vs. 9.20 g/m2) compared to CM-0 (PP:CM 10:0). After 30 days of indoor storage, the filtration efficiency of CM-2 remained above 94%. The self-curling melt-blown filtration material developed here could potentially be applied in the field of protective masks.

NUCLEOLIN PROMOTES AUTOPHAGY THROUGH PGC-1Α IN LPS-INDUCED MYOCARDIAL INJURY.

ABSTRACT: As a multifunctional protein, nucleolin can participate in a variety of cellular processes. Nucleolin also has multiple protective effects on heart disease. Previous studies have shown that nucleolin could not only resist oxidative stress damage and inflammatory damage, but also regulate autophagy to play a protective role in cardiac ischemia. However, the specific mechanism has not been fully elucidated in LPS-induced myocardial injury. Therefore, the aim of this study is to explore the underlying mechanism by which nucleolin regulates autophagy to protect against LPS-induced myocardial injury in vivo and in vitro . In our study, we found that nucleolin could bind to PGC-1α, and we predicted that this interaction could promote autophagy and played a role in inhibiting cardiomyocyte apoptosis. Downregulation of nucleolin in H9C2 cells resulted in decreased autophagy and increased cell apoptosis during LPS-induced myocardial injury, while upregulation of PGC-1α had the opposite protective effect. Upregulation of nucleolin expression in cardiomyocytes could increase the level of autophagy during LPS-induced myocardial injury. In contrast, interference with PGC-1α expression resulted in a decrease in the protective effect of nucleolin, leading to reduced autophagy and thus increasing apoptosis. By using tandem fluorescent-tagged LC3 autophagic flux detection system, we observed autophagic flux and determined that PGC-1α interference could block autophagic lysosomal progression. We further tested our hypothesis in the nucleolin cardiac-specific knockout mice. Finally, we also found that inhibition of autophagy can reduce mitochondrial biogenesis as well as increase apoptosis, which demonstrated the importance of autophagy. Therefore, we can speculate that nucleolin can protect LPS-induced myocardial injury by regulating autophagy, and this protective effect may be mediated by the interaction with PGC-1α, which can positively regulate the ULK1, an autophagy-related protein. Our study provides a new clue for the cardioprotective effect of nucleolin, and may provide new evidence for the treatment of LPS-induced myocardial injury through the regulation of autophagy.

Examining the effect of logistics service quality on customer satisfaction and re-use intention.

For logistics service providers (LSPs), improving customer satisfaction and obtaining customer re-use intention are key to gaining sustainable competitive advantages and success. Logistics service quality (LSQ) is a concern for logistics service providers, retailers, and customers. The proposed model, which is based on the stimuli-organism-response theory and the logistics service quality framework, integrates operational quality, resource quality, information quality, personal contact quality, customization quality, and customer satisfaction to study logistics service re-use intentions. The data were obtained from an online survey using a structured questionnaire given to those with experience in logistics service. Using partial least squares structural equation modeling on 810 respondents who were adult Chinese customers, this study discovered that operational, resource, information, personal contact, and customization qualities positively affect the satisfaction of logistics service customers, while customer satisfaction positively affects re-use intention. Moreover, the results of the mediation analysis revealed that customer satisfaction mediated the connection between the five components of LSQ and the re-use intention of logistics services. The originality of the study lies in its comprehensive examination of the direct and indirect effects of service quality dimensions on customer satisfaction and logistics service re-use intention in the context of logistics services. This study provides valuable insights into the importance of customer satisfaction in the logistics industry and highlights the need for logistics companies to prioritize customer satisfaction and improve their overall performance and competitiveness.

Network of miR396-mRNA in Tissue Differentiation in Moso Bamboo (Phyllostachys edulis).

MiR396 plays an essential role in various developmental processes. However, the miR396-mRNA molecular network in bamboo vascular tissue differentiation during primary thickening has not been elucidated. Here, we revealed that three of the five members from the miR396 family were overexpressed in the underground thickening shoots collected from Moso bamboo. Furthermore, the predicted target genes were up/down-regulated in the early (S2), middle (S3) and late (S4) developmental samples. Mechanistically, we found that several of the genes encoding protein kinases (PKs), growth-regulating factors (GRF), transcription factors (TFs), and transcription regulators (TRs) were the potential targets of miR396 members. Moreover, we identified QLQ (Gln, Leu, Gln) and WRC (Trp, Arg, Cys) d omains in five PeGRF homologs and a Lipase_3 domain and a K_trans domain in another two potential targets, where the cleavage targets were identified via degradome sequencing (p < 0.05). The sequence alignment indicated many mutations in the precursor sequence of miR396d between Moso bamboo and rice. Our dual-luciferase assay revealed that ped-miR396d-5p binds to a PeGRF6 homolog. Thus, the miR396-GRF module was associated with Moso bamboo shoot development. Fluorescence in situ hybridization localized miR396 in the vascular tissues of the leaves, stems, and roots of pot Moso bamboo seedlings at the age of two months. Collectively, these experiments revealed that miR396 functions as a regulator of vascular tissue differentiation in Moso bamboo. Additionally, we propose that miR396 members are targets for bamboo improvement and breeding.

The role of Transmembrane Protein 16A (TMEM16A) in pulmonary hypertension.

Transmembrane protein 16A (TMEM16A), a member of the TMEM16 family, is the molecular basis of Ca2+-activated chloride channels (CaCCs) and is involved in a variety of physiological and pathological processes. Previous studies have focused more on respiratory-related diseases and tumors. However, recent studies have identified an important role for TMEM16A in cardiovascular diseases, especially in pulmonary hypertension. TMEM16A is expressed in both pulmonary artery smooth muscle cells and pulmonary artery endothelial cells and is involved in the development of pulmonary hypertension. This paper presents the structure and function of TMEM16A, the pathogenesis of pulmonary hypertension, and highlights the role and mechanism of TMEM16A in pulmonary hypertension, summarizing the controversies in this field and taking into account hypertension and portal hypertension, which have similar pathogenesis. It is hoped that the unique role of TMEM16A in pulmonary hypertension will be illustrated and provide ideas for research in this area.

LncRNA Fendrr: involvement in the protective role of nucleolin against H2O2-induced injury in cardiomyocytes.

Background: Nucleolin is a multifunctional nucleolar protein with RNA-binding properties. Increased nucleolin expression protects cells from H2O2-induced damage, but the mechanism remains unknown. Long noncoding RNAs (lncRNAs) play crucial roles in cardiovascular diseases. However, the biological functions and underlying mechanisms of lncRNAs in myocardial injury remain unclear.Methods: In a nucleolin-overexpressing cardiac cell line, high-throughput technology was used to identify lncRNAs controlled by nucleolin. Cell counting kit-8 assay was used to determine cell viability, lactate dehydrogenase (LDH) assay to detect cell death, caspase activity assay and propidium iodide staining to confirm cell apoptosis, and RNA immunoprecipitation to examine the interaction between Fendrr and nucleolin.Results: We found that Fendrr expression was significantly downregulated in mouse hearts subjected to myocardial ischemia-reperfusion (MI/R) injury. High Fendrr expression abrogated H2O2-mediated injury in cardiomyocytes as evidenced by increased cell viability and decreased cell apoptosis. Conversely, Fendrr knockdown exacerbated the cardiomyocytes injury. Also, nucleolin overexpression inhibits Fendrr downregulation in H2O2-induced cardiomyocyte injury. Fendrr overexpression significantly reversed the role of the suppression of nucleolin expression in H2O2-induced cardiomyocytes.Conclusion: LncRNA Fendrr is involved in the cardioprotective effect of nucleolin against H2O2-induced injury and may be a potential therapeutic target for oxidative stress-induced myocardial injury.

NUCLEOLIN PROTECTS CARDIOMYOCYTES BY UPREGULATING PGC-1α AND PROMOTING MITOCHONDRIAL BIOGENESIS IN LPS-INDUCED MYOCARDIAL INJURY.

ABSTRACT: Background: Lipopolysaccride-induced myocardial injury was characterized by frequent mitochondrial dysfunction. Our previous studies found that nucleolin (NCL) played important protective roles in myocardial ischemia-reperfusion injury. Recently, it has been found that NCL has a protective effect on LPS-induced myocardial injury in vivo . However, the exact underlying mechanisms that how NCL protects myocardium against the LPS-induced myocardial injury remains unclear. Objective: The aim of the study is to investigate the protective role of NCL in LPS-induced myocardial injury from the aspect of mitochondrial biogenesis. Methods: The cardiac-specific NCL-knockout (NCL -/- ) or NCL f/f mice were injected with LPS (10 mg/kg) to induce LPS-induced myocardial injury. The supernatant generated after LPS stimulation of macrophages was used as the conditioned medium to stimulate H9C2 and established the injured cell model. Analysis of mRNA stability, RNA-binding protein immunoprecipitation assay, and luciferase reporter assay were performed to detect the mechanism by which NCL regulated the expression of PGC-1α. Results: The expression of NCL and PGC-1α was elevated in cardiac tissue and cardiomyocytes during LPS-induced myocardial injury. The cardiac-specific NCL-knockout decreased PGC-1α expression, inhibited mitochondrial biogenesis, and increased cardiomyocytes death during LPS-induced myocardial injury in vitro and in vivo . In contrast, the overexpression of NCL could improve mitochondrial biogenesis in H9C2 cells. Moreover, the analysis of mRNA stability and luciferase reporter assay revealed that the interaction between NCL and PGC-1α significantly promoted the stability of PGC-1α mRNA, thereby upregulating the expression of PGC-1α and exerting a cardioprotective effect. In addition, the activation of PGC-1α diminished the detrimental effects of NCL knockdown on mitochondrial biogenesis in vitro and in vivo . Conclusions: Nucleolin upregulated the gene expression of PGC-1α by directly binding to the 5'-UTR of PGC-1α mRNA and increasing its mRNA stabilities, then promoted mitochondrial biogenesis, and played protective effect on cardiomyocytes during LPS-induced myocardial injury. Taken together, all these data showed that NCL activated PGC-1α to rescue cardiomyocytes from LPS-induced myocardial injury insult, suggesting that the cardioprotective role of NCL might be a promising prospect for clinical treatment of patients with endotoxemia.

tRNA-Derived Small RNAs: Novel Insights into the Pathogenesis and Treatment of Cardiovascular Diseases.

tRNA-derived small RNAs (tsRNAs) are non-coding RNAs with diverse functions in various diseases. Although research on tsRNAs has focused on their roles in cancer, such as gene expression regulation to influence cancer progression and realize clinical effects, a growing number of studies are investigating the association of tsRNAs with cardiovascular diseases (CVDs), including atherosclerosis, myocardial infarction, and pulmonary hypertension. tsRNA expression varies across these diseases and could be regulated by epigenetics, tsRNA structure, and tRNA-binding proteins. tsRNAs play key roles in CVD progression, including the regulation of protein synthesis, and the different mechanisms underlying these functional roles of tsRNAs have been elucidated. Furthermore, tsRNAs are potential diagnostic biomarkers and therapeutic targets in CVDs. In this review, we summarize the biogenesis, classification, and regulation of tsRNAs and their potential application for CVD diagnosis and therapy. We also highlight the current challenges and provide perspectives for further investigation.

Water Intake and Hydration Status among Pregnant Women in the Second Trimester in China: A Three-Day Metabolic Trial.

Adequate water intake and optimal hydration status during pregnancy are crucial for maternal and infant health. However, research on water intake by pregnant women in China is very limited. This study mainly aimed to observe the daily total water intake (TWI) of pregnant women and its different sources and to investigate the relationship between their water intake and hydration biomarkers. From October to November 2020, a convenience sample of pregnant women in the second trimester (n = 21) was recruited. Under conditions close to daily life, they undertook a 3-day metabolic trial. Each participant was provided with sufficient bottled water, and the weight of what they drank each time was measured. The intake of other beverages and foods was measured using a combination of weighing and duplicate portion method. Fasting venous blood and 24 h urine samples were collected and analyzed for the hydration biomarkers, including the serum/urine osmolality, urine pH, urine specific gravity, and the concentrations of major electrolytes in urine and serum. The results showed that the mean daily TWI was 3151 mL, of which water from beverages and foods accounted for 60.1% and 39.9%, respectively. The mean total fluid intake (TFI) was 1970 mL, with plain water being the primary contributor (68.7%, r = 0.896). Among the participants, 66.7% (n = 14, Group 1) met the TWI recommendation set by the Chinese Nutrition Society. Further analysis revealed that the TFI, water from beverages and foods, plain water, and milk and milk derivatives (MMDs) were significantly higher in Group 1 than those who did not reach the adequate intake value (Group 2) (p < 0.05). The results of hydration biomarkers showed that the mean 24 h urine volume in Group 1 was significantly higher than that in Group 2 (p < 0.05), while the 24 h urine osmolality, sodium, magnesium, phosphorus, chloride, and creatinine concentrations in Group 1 were significantly lower than those in Group 2 (p < 0.05). However, no significant differences were observed in serum biomarkers. Partial correlation analysis showed that TWI was moderately positively correlated with 24 h urine volume (r = 0.675) and negatively correlated with urine osmolality, sodium, potassium, magnesium, calcium, phosphorus, and chloride concentrations (r = from-0.505 to -0.769), but it was not significantly correlated with serum biomarkers. Therefore, under free-living conditions, increasing the daily intake of plain water and MMDs is beneficial for pregnant women to maintain optimal hydration. The hydration biomarkers in urine are more accurate indicators of water intake and exhibit greater sensitivity compared to serum biomarkers. These findings provide a scientific basis for establishing appropriate water intake and hydration status for pregnant women in China.