Allogeneic platelet-rich plasma for knee osteoarthritis in patients with primary immune thrombocytopenia: A randomized clinical trial.

The treatment of painful KOA in adult patients with ITP has not been well studied yet. We conducted a prospective, double-blind, randomized, placebo-controlled trial to evaluate the efficacy of intra-articular allogeneic PRP injections on symptoms and joint structure in patients with KOA and ITP. 80 participants were randomly allocated in a 1:1 ratio to allogeneic PRP group or saline group. The primary outcome was the WOMAC total score at 12 months post-injection. The number of patients in each group who achieved MCID of primary outcome showed a statistically significant difference only at 3-month (27/39 vs. 5/39, p = 0.001) and 6-month (15/39 vs. 3/38, p = 0.032). The difference in WOMAC total score exceeded the MCID only at 3 month (mean difference of -15.1 [95% CI -20.7 to -9.5], p < 0.001). Results suggest that allogeneic PRP was superior to placebo only with respect to symptoms at 3-month of follow-up.

Computational modeling of Chlamydomonas reinhardtii cellular radiation properties with synergistic consideration of complex structures and compositions.

The radiation characteristics of microalgae are of great significance for the design of photobioreactors and ocean optical remote sensing. Yet the complex structure of microalgae makes it difficult to theoretically predict its radiation characteristics based on traditional Mie theory. In this work, taking Chlamydomonas reinhardtii as an example, a multi-component cell model with a complex structure is proposed, which considers the organelles and shape of microalgae, and the volume change during the production of Chlamydomonas reinhardtii lipids. The theoretical calculation is carried out using the discrete dipole approximation method, and an improved transmission method is used for experimental measurement. The experimental data are compared and analyzed with the multi-component complex structure model, the homogeneous sphere model and the coated sphere model. The results show that the calculation accuracy of the multi-component complex structure model is higher, the error of the scattering cross-section is reduced by more than 8.6% compared with the homogeneous sphere model and coated sphere model, and the absorption cross-section and the scattering phase function are in good agreement with the experimental results. With the increase of lipids, the absorption cross-section and the scattering phase function vary slightly. However, the scattering cross-section has an observed change with increasing wavelength. In addition, the theoretical calculation error can be reduced when the influence of the culture medium is taken into account.

LC-MS based metabonomics study on protective mechanism of ESWW in cerebral ischemia via CYTC/Apaf-1/NDRG4 pathway.

BACKGROUND: Ershiwuwei Zhenzhu pills was originally recorded in the Tibetan medical book Si Bu Yi Dian in the 8th century AD and is now included in the Pharmacopoeia of the People's Republic of China (2020). The pills can calm the nerves and open the mind as well as treat cerebral ischemia reperfusion injury, stroke, hemiplegia. However, its quality standards have not yet been established, and the therapeutic effect on cerebral ischemia by regulating the mitochondrial apoptosis pathway has not been elucidated. STUDY DESIGN AND METHODS: LC-MS was used to establish quality standards for Ershiwuwei Zhenzhu pills. Metabonomics, molecular docking, neuroethology, cerebral infarction ratio, pathological detection of diencephalon, cortex, and hippocampus, and molecular biology techniques were used to reveal the mechanism of the pills in regulating the mitochondrial apoptosis pathway to treat cerebral ischemia. RESULTS: The contents of 20 chemical components in Ershiwuwei Zhenzhu pills from 12 batches and 8 manufacturers was determined for the first time. Eleven differential metabolites and three metabolic pathways, namely, fructose and mannose metabolism, glycerophospholipid metabolism, and purine metabolism, were identified by metabonomics. The pills improved the neuroethology abnormalities of MCAO rats and the pathological damage in the diencephalon and decreased the ratio of cerebral infarction. It also significantly reduced the mRNA expression of AIF, Apaf-1, cleared caspase8, CytC, and P53 mRNA in the brain tissue and the protein expression of Apaf-1 and CYTC and increased the protein expression of NDRG4. CONCLUSION: In vitro quantitative analysis of the in vitro chemical components of Ershiwuwei Zhenzhu pills has laid the foundation for improving its quality control. The potential mechanism of the pills in treating cerebral ischemia may be related to the Apaf-1/CYTC/NDRG4 apoptosis pathway. This work provides guidance for clinical drug use for patients.

Artificial Intelligence-driven Platform: Unveiling Critical Hepatic Molecular Alterations in Hepatocellular Carcinoma Development.

Since most Hepatocellular Carcinoma (HCC) typically arises as a consequence of long-term liver damage, the hepatic molecular characteristics are closely related to the occurrence of HCC. Gaining comprehensive information about the location, morphology, and hepatic molecular alterations related to HCC is essential for accurate diagnosis. However, there is a dearth of technological advancements capable of concurrently providing precise HCC diagnosis and discerning the accompanying hepatic molecular alterations. In this study, We have developed an integrated information system for the pathological-level diagnosis of HCC and the revelation of critical molecular alterations in the liver. This system utilizes computed tomography/Surface-enhanced Raman scattering combined with an artificial intelligence strategy to establish connections between the occurrence of HCC and alterations in hepatic biomolecules. Employing artificial intelligence techniques, the SERS spectra from both healthy and HCC groups were successfully classified into two distinct categories with a remarkable accuracy rate of 91.38%. Based on molecular profiling, we have identified that the nucleotide-to-lipid signal ratio holds significant potential as a reliable indicator for the occurrence of HCC, thereby serving as a promising tool for prevention and therapeutic surveillance. This article is protected by copyright. All rights reserved.

Incidence of deep venous thrombosis in patients with hemophilia undergoing bilateral simultaneous total knee arthroplasty: a retrospective cohort study.

BACKGROUND: Hemophilic arthropathy usually affects the knees bilaterally. In order to reduce costs and improve rehabilitation, bilateral simultaneous total knee arthroplasty (TKA) can be performed. However, pharmacological prophylaxis for deep venous thrombosis (DVT) remains controversial in patients with severe hemophilia. The purpose of this study was to establish the incidence of DVT in severe hemophilia A patients undergoing bilateral simultaneous TKA without pharmacological thromboprophylaxis. METHODS: Consecutive patients with severe hemophilia A undergoing bilateral simultaneous TKA at a single center between January 2015 and December 2020 were retrospectively reviewed. All patients received a modified coagulation factor substitution regimen. Tranexamic acid (TXA) was used for hemostasis in all patients during surgery. All patients followed a standardized postoperative protocol with routine mechanical thromboprophylaxis, and none received anticoagulation. D-dimer was measured preoperatively, on the day of the operation and on postoperative days 1, 7 and 14. Ultrasound (US) of the lower extremities was performed before (within 3 days of hospitalization) and after surgery (days 3 and 14) to detect asymptomatic DVT. Patients were followed up until 2 years after surgery for the development of symptomatic DVT or pulmonary embolism (PE). RESULTS: 38 male patients with severe hemophilia A underwent 76 simultaneous TKAs. Mean (± standard deviation) age at the time of operation was 41.7 (± 17.1) years. Overall, 47.3% of patients had D-dimer concentrations above the threshold 10 µg/mL on day 7 and 39.5% on day 14. However, none of the patients had DVT detected on postoperative US, nor developed symptomatic DVT or PE during the 2-year follow-up. CONCLUSIONS: The risk of DVT in patients with severe hemophilia A after bilateral simultaneous TKA is relatively low, and routine pharmacological thromboprophylaxis may not be needed.

Field-Free Spin-Orbit Torque Magnetization Switching in a Perpendicularly Magnetized Semiconductor (Ga,Mn)As Single Layer.

Current-induced spin-orbit torque (SOT) in a perpendicularly magnetized single layer has a strong potential to switch the magnetization using an extremely low current density, which is generally 2-3 orders of magnitude smaller than that required for conventional metal bilayer systems. However, an in-plane external magnetic field has to be applied to break the symmetry and achieve deterministic switching. To further enhance the high-density integration and accelerate the practical application of highly efficient SOT magnetic random-access memory (SOT-MRAM) devices, field-free SOT magnetization switching in a ferromagnetic single layer is strongly needed. In a spin-orbit ferromagnet (a ferromagnet with strong spin-orbit interaction) with crystal inversion asymmetry and a multi-domain structure, the internal Dzyaloshinskii-Moriya effective fields are considered to induce field-free switching. Here, combined with strong spin-orbit coupling and a tilted anisotropy axis induced by a nonuniform Mn distribution and a possible magnetocrystalline anisotropy resulting from a slight substrate tilting, we successfully achieve magnetization switching in a spin-orbit ferromagnet (Ga,Mn)As single layer by utilizing SOT without applying any external magnetic field. Our findings help to deeply elucidate the SOT switching mechanism and can advance the development of a highly efficient MRAM with better scalability.

The Efficacy of Neuromodulation Interventions for Chemotherapy-Induced Peripheral Neuropathy: A Systematic Review and Meta-Analysis.

Purpose: To determine the efficacy and safety of a neuromodulation intervention regimen in the treatment of chemotherapy-induced peripheral neuropathy (CIPN). Patients and Methods: Systematic searches were conducted in seven English databases. Randomized controlled trials of all neuromodulation interventions (both invasive and non-invasive) for the treatment of CIPN were selected. Group comparisons of differences between interventions and controls were also made. We divided the outcomes into immediate-term effect (≤3 weeks), short-term effect (3 weeks to ≤3 months), and long-term effect (>3 months). Results: Sixteen studies and 946 patients with CIPN were included. Among immediate-term effects, neuromodulation interventions were superior to usual care for improving pain (SMD=-0.77, 95% CI -1.07~ 0.47), FACT-Ntx (MD = 5.35, 95% CI 2.84~ 7.87), and QOL (SMD = 0.44, 95% CI 0.09~ 0.79) (moderate certainty); neuromodulation loaded with usual care was superior to usual care for improving pain (SMD=-0.47, 95% CI -0.71 ~ -0.23), and QOL (SMD = 0.40, 95% CI 0.12 ~ 0.69) (moderate certainty). There were no statistically significant differences between the neuromodulation interventions regimen vs usual care in short- and long-term outcomes and neuromodulation vs sham stimulation from any outcome measure. There were mild adverse events such as pain at the site of stimulation and bruising, and no serious adverse events were reported. Conclusion: Neuromodulation interventions had significant immediate-term efficacy in CIPN but had not been shown to be superior to sham stimulation; short-term and long-term efficacy could not be determined because there were too few original RCTs. Moreover, there are no serious adverse effects of this therapy.

Serotonin receptor 2B induces visceral hyperalgesia in rat model and patients with diarrhea-predominant irritable bowel syndrome.

BACKGROUND: Serotonin receptor 2B (5-HT2B receptor) plays a critical role in many chronic pain conditions. The possible involvement of the 5-HT2B receptor in the altered gut sensation of irritable bowel syndrome with diarrhea (IBS-D) was investigated in the present study. AIM: To investigate the possible involvement of 5-HT2B receptor in the altered gut sensation in rat model and patients with IBS-D. METHODS: Rectosigmoid biopsies were collected from 18 patients with IBS-D and 10 patients with irritable bowel syndrome with constipation who fulfilled the Rome IV criteria and 15 healthy controls. The expression level of the 5-HT2B receptor in colon tissue was measured using an enzyme-linked immunosorbent assay and correlated with abdominal pain scores. The IBS-D rat model was induced by intracolonic instillation of acetic acid and wrap restraint. Alterations in visceral sensitivity and 5-HT2B receptor and transient receptor potential vanilloid type 1 (TRPV1) expression were examined following 5-HT2B receptor antagonist administration. Changes in visceral sensitivity after administration of the TRPV1 antagonist were recorded. RESULTS: Here, we observed greater expression of the 5-HT2B receptor in the colonic mucosa of patients with IBS-D than in that of controls, which was correlated with abdominal pain scores. Intracolonic instillation of acetic acid and wrap restraint induced obvious chronic visceral hypersensitivity and increased fecal weight and fecal water content. Exogenous 5-HT2B receptor agonist administration increased visceral hypersensitivity, which was alleviated by successive administration of a TRPV1 antagonist. IBS-D rats receiving the 5-HT2B receptor antagonist exhibited inhibited visceral hyperalgesia.Moreover, the percentage of 5-HT2B receptor-immunoreactive (IR) cells surrounded by TRPV1-positive cells (5-HT2B receptor I+) and total 5-HT2B receptor IR cells (5-HT2B receptor IT) in IBS-D rats was significantly reduced by the administration of a 5-HT2B receptor antagonist. CONCLUSION: Our finding that increased expression of the 5-HT2B receptor contributes to visceral hyperalgesia by inducing TRPV1 expression in IBS-D patients provides important insights into the potential mechanisms underlying IBS-D-associated visceral hyperalgesia.

Impact of COVID-19 Nonpharmaceutical Interventions on Respiratory Syncytial Virus Infections in Hospitalized Children.

BACKGROUND: Nonpharmaceutical interventions (NPIs) targeted at SARS-CoV-2 have remarkably affected the circulation of other respiratory pathogens, including respiratory syncytial virus (RSV). This study aimed to assess the changes in epidemiological and clinical characteristics of RSV infections in hospitalized children before and during the pandemic in Suzhou, China. METHODS: We prospectively enrolled children aged < 18 years who were hospitalized in Soochow University Affiliated Children's Hospital with acute lower respiratory infection (ALRIs) from January 2018 to July 2022. Changes in epidemiological and clinical characteristics of RSV infections were analyzed. RESULTS: Compared with the same period in 2018-2019, the difference in the overall positive rate of RSV was not statistically significant in 2020, while it increased significantly in 2021 (11.8% [662/5621] vs. 20.8% [356/1711], p < 0.001) and 2022 (9.0% [308/3406] vs. 18.9% [129/684], p < 0.001). Specifically, the positive rates declined considerably from October to December 2020 but sharply increased during the summer of 2021. Compared to prepandemic period, RSV infections were more frequently observed in older children during the pandemic. RSV-positive children exhibited milder clinical characteristics during the COVID-19 pandemic, including decreased proportion of patients with hospital stay ≥ 11 days (10.3% vs. 6.7%, p < 0.05), less requirement for oxygen therapy (13.7% vs. 6.9%, p < 0.001), and fewer cases of polypnea (12.2% vs. 9.7%, p < 0.05) and wheeze (50.1% vs. 42.9%, p < 0.001). CONCLUSIONS: The implementation of multilayered NPIs targeted at COVID-19 has affected the activity of RSV. Ongoing monitoring of RSV is warranted as the changing RSV epidemiology can provide valuable insights for future healthcare system planning.

Theoretical and experimental study on the radiative properties of Parachlorella kessleri: considering the effect of internal microstructure.

A microalgal cell model with multiple organelles considering both the irregular overall shape and internal microstructure was proposed. The radiative properties of Parachlorella kessleri during the normal phase, starch-rich phase, and lipid-rich phase were calculated by the discrete dipole approximation method in the visible wavelengths. The accuracy of the model is verified with experimental measurements. The results showed that the theoretical calculation of the established microalgal cell model is more accurate than those of the equal volume spheres, such as the homogeneous sphere and the coated sphere, with the errors of the scattering cross-section reduced by more than 10.7%. The calculated scattering phase function of the multi-component model is basically in good agreement with the experimental results. Compared to the normal growth phase, the lipid enrichment during the lipid-rich phase leads to a sharp increase in the scattering cross-section by three to four times, while the absorption cross-section remains stable. Remarkably, in the starch-rich phase, the abundant production of starch results in a reduction of two to three times in the absorption cross-section compared to the normal growth phase, while the scattering cross-section varies little. The results can provide basic data and theoretical support for the design and optimization of photobioreactors.

Coenzyme Q10 in atherosclerosis.

Atherosclerotic disease is a chronic disease that predominantly affects the elderly and is the most common cause of cardiovascular death worldwide. Atherosclerosis is closely related to processes such as abnormal lipid transport and metabolism, impaired endothelial function, inflammation, and oxidative stress. Coenzyme Q10 (CoQ10) is a key component of complex Ⅰ in the electron transport chain and an important endogenous antioxidant that may play a role in decelerating the progression of atherosclerosis. Here, the different forms of CoQ10 presence in the electron transport chain are reviewed, as well as its physiological role in regulating processes such as oxidative stress, inflammatory response, lipid metabolism and cellular autophagy. It was also found that CoQ10 plays beneficial effects in atherosclerosis by mitigating lipid transportation, endothelial inflammation, metabolic abnormalities, and thrombotic processes from the perspectives of molecular mechanisms, animal experiments, and clinical evidence. Besides, the combined use of CoQ10 with other drugs has better synergistic therapeutic effects. It seems reasonable to suggest that CoQ10 could be used in the treatment of atherosclerotic cardiovascular diseases while more basic and clinical studies are needed.

Endothelial Slc35a1 Deficiency Causes Loss of LSEC Identity and Exacerbates Neonatal Lipid Deposition in the Liver in Mice.

BACKGROUND & AIMS: The functional maturation of the liver largely occurs after birth. In the early stages of life, the liver of a newborn encounters enormous high-fat metabolic stress caused by the consumption of breast milk. It is unclear how the maturing liver adapts to high lipid metabolism. Liver sinusoidal endothelial cells (LSECs) play a fundamental role in establishing liver vasculature and are decorated with many glycoproteins on their surface. The Slc35a1 gene encodes a cytidine-5'-monophosphate (CMP)-sialic acid transporter responsible for transporting CMP-sialic acids between the cytoplasm and the Golgi apparatus for protein sialylation. This study aimed to determine whether endothelial sialylation plays a role in hepatic vasculogenesis and functional maturation. METHODS: Endothelial-specific Slc35a1 knockout mice were generated. Liver tissues were collected for histologic analysis, lipidomic profiling, RNA sequencing, confocal immunofluorescence, and immunoblot analyses. RESULTS: Endothelial Slc35a1-deficient mice exhibited excessive neonatal hepatic lipid deposition, severe liver damage, and high mortality. Endothelial deletion of Slc35a1 led to sinusoidal capillarization and disrupted hepatic zonation. Mechanistically, vascular endothelial growth factor receptor 2 (VEGFR2) in LSECs was desialylated and VEGFR2 signaling was enhanced in Slc35a1-deficient mice. Inhibition of VEGFR2 signaling by SU5416 alleviated lipid deposition and restored hepatic vasculature in Slc35a1-deficient mice. CONCLUSIONS: Our findings suggest that sialylation of LSECs is critical for maintaining hepatic vascular development and lipid homeostasis. Targeting VEGFR2 signaling may be a new strategy to prevent liver disorders associated with abnormal vasculature and lipid deposition.

Effect of freeze-thaw frequency plus rainfall on As and Sb metal(loid)s leaching from the solidified/stabilized soil remediated with Fe-based composite agent.

The composite agent of ferrous sulfate, fly ash, and calcium lignosulfonate (FFC) can remediate the soil contaminated by As and Sb under cyclic freeze-thaw (F-T) via stabilization/solidification (S/S). However, the impact of high-frequency F-T cycles on the leaching behavior and migration of As and Sb in FFC-treated soils remains unclear. Here the leaching concentrations, heavy metal speciation (Wenzel's method), and Hydrus-1d simulations were investigated. The results showed that FFC effectively maintained the long-term S/S efficiency of arsenic remediation subject to an extended rainfall and freeze-thaw cycles, and stabilized the easily mobile form of As. The short-term S/S effect on Sb in the remediated soils suffering from F-T cycles was demonstrated in the presence of FFC. In a 20-year span, the mobility of Sb was affected by the number of F-T cycles (FT60 > FT20 > FT40 > FT0) in soil with a depth of 100 cm. As leaching progressed, FFC slowed the upward proportion of adsorbed As fractions but converted parts of the residual Sb to the form of crystalline Fe/Al (hydro) oxide. Moreover, the adsorption rate and capacity of As also preceded that of Sb. Long-term curative effects of FFC could be observed for As, but further development of agents capable of remedying Sb under cyclic F-T and long-term rainfall was needed. The predictive results on the migration and leaching behavior of heavy metals in S/S remediated soils may provide new insight into the long-term assessment of S/S under natural conditions.

MicroRNAs in spermatogenesis dysfunction and male infertility: clinical phenotypes, mechanisms and potential diagnostic biomarkers.

Infertility affects approximately 10-15% of couples worldwide who are attempting to conceive, with male infertility accounting for 50% of infertility cases. Male infertility is related to various factors such as hormone imbalance, urogenital diseases, environmental factors, and genetic factors. Owing to its relationship with genetic factors, male infertility cannot be diagnosed through routine examination in most cases, and is clinically called 'idiopathic male infertility.' Recent studies have provided evidence that microRNAs (miRNAs) are expressed in a cell-or stage-specific manner during spermatogenesis. This review focuses on the role of miRNAs in male infertility and spermatogenesis. Data were collected from published studies that investigated the effects of miRNAs on spermatogenesis, sperm quality and quantity, fertilization, embryo development, and assisted reproductive technology (ART) outcomes. Based on the findings of these studies, we summarize the targets of miRNAs and the resulting functional effects that occur due to changes in miRNA expression at various stages of spermatogenesis, including undifferentiated and differentiating spermatogonia, spermatocytes, spermatids, and Sertoli cells (SCs). In addition, we discuss potential markers for diagnosing male infertility and predicting the varicocele grade, surgical outcomes, ART outcomes, and sperm retrieval rates in patients with non-obstructive azoospermia (NOA).

Report of abnormal tail regeneration of Eremias yarkandensis (Sauria: Lacertidae) and its locomotor performance.

Caudal autotomy is a phenomenon observed in many reptile taxa, and tail loss is a pivotal functional trait for reptiles, with potentially negative implications for organism fitness due to its influence on locomotion. Some lizard species can regenerate a lost tail, which sometimes can lead to the development of more than one tail (i.e., abnormal tail regeneration) in the process. However, little is currently known about the impact of abnormal tail regeneration on locomotor performance. In this study, we document abnormal tail regeneration in Eremias yarkandensis, a reptile species native to northwestern China. Additionally, we investigated the sprint speed and endurance performance of these lizards. This study provides the first report on abnormal tail regeneration and its locomotor performance on a Chinese reptile. We suggest that the abnormal regeneration of tails may contribute to the accumulation of food reserves in the species. In light of our findings, we propose that herpetologists continue to share their sporadic observations and assess the locomotor performance of species experiencing abnormal tail regeneration, further expanding our understanding of this intriguing phenomenon.

Gastrodinol derivatives and prenylated flavones from the flower branch of Gastrodia elata.

Based on the research progress and traditional usage with whole herbal of the TCM "Tianma", chemical studies herein on the flower branch of Gastrodia elata were carried out in-depth and got 13 compounds including the gastrodinols (1-4), the flavonoid morins (5-8, 11-12), together with the specialist mulberrofurans (9, 13) and gastrodiamide (10) for the first time from the species. The antibacterial and cholinesterase inhibitory activities were then evaluated and the results showed that compounds 5, 11, 12, 13 have good activity against anti-methicillin-resistant Staphylococcus aureus, and compounds 9, 13 had good acetylcholinesterase inhibitory activity. All these results provide new chemical composition for better understanding the traditional application of "Tianma" and for exploring new pharmacological ingredients.

Herbal medicines provide regulation against iron overload in cardiovascular diseases: Informing future applications.

ETHNOPHARMACOLOGICAL RELEVANCE: Iron is an essential micronutrient for maintaining physiological activities, especially for highly active cardiomyocytes. Inappropriate iron overload or deficiency has a significant impact on the incidence and severity of cardiovascular diseases (CVD). Iron overload exerts potentially deleterious effects on doxorubicin (DOX) cardiomyopathy, atherosclerosis, and myocardial ischemia-reperfusion injury (MI/RI) by participating in lipid peroxides production. Notably, iron overload-associated cell death has been defined as a possible mechanism for ferroptosis. At present, some traditional herbal medicines and extracts have been included in the study of regulating iron overload and the subsequent therapeutic effect on CVD. AIM OF THE STUDY: To give an outline of iron metabolism and ferroptosis in cardiomyocytes and to focus on herbal medicines and extracts to prevent iron overload in CVD. MATERIALS AND METHODS: Literature information was systematically collected from ScienceDirect, PubMed, Google Scholar, Web of Science, China National Knowledge Infrastructure, WanFang data, as well as classic books and clinical reports. RESULTS: After understanding the mechanism of iron overload on CVD, this paper reviews the therapeutic function of various herbal medicines in eliminating iron overload in CVD. These include Chinese herbal compound prescriptions (Salvia miltiorrhiza injection, Gegen Qinlian decoction, Tongxinluo, Banxia-Houpu decoction), plant extracts, phenylpropanoids, flavonoids, terpenoids, and polyphenols. Among them, flavonoids are considered to be the most promising compounds because of their prominent iron chelation. Mechanically, these herbal medicines act on the Nrf2 signaling pathway, AMPK signaling pathway, and KAT5/GPX4 signaling pathway, thereby attenuating iron overload and lipid peroxidation in CVD. CONCLUSION: Our review provides up-to-date information on herbal medicines that exert cardiovascular protective effects by modulating iron overload and ferroptosis. These herbal medicines hold promise as a template for preventing iron overload in CVD.

TRIM65 promotes vascular smooth muscle cell phenotypic transformation by activating PI3K/Akt/mTOR signaling during atherogenesis.

BACKGROUND AND AIMS: Tripartite motif (TRIM65) is an important member of the TRIM protein family, which is a newly discovered E3 ligase that interacts with and ubiquitinates various substrates and is involved in diverse pathological processes. However, the function of TRIM65 in atherosclerosis remains unarticulated. In this study, we investigated the role of TRIM65 in the pathogenesis of atherosclerosis, specifically in vascular smooth muscle cells (VSMCs) phenotype transformation, which plays a crucial role in formation of atherosclerotic lesions. METHODS AND RESULTS: Both non-atherosclerotic and atherosclerotic lesions during autopsy were collected singly or pairwise from each individual (n = 16) to investigate the relationship between TRIM65 and the development of atherosclerosis. In vivo, Western diet-fed ApoE-/- mice overexpressing or lacking TRIM65 were used to assess the physiological function of TRIM65 on VSMCs phenotype, proliferation and atherosclerotic lesion formation. In vitro, VSMCs phenotypic transformation was induced by platelet-derived growth factor-BB (PDGF-BB). TRIM65-overexpressing or TRIM65-abrogated primary mouse aortic smooth muscle cells (MOASMCs) and human aortic smooth muscle cells (HASMCs) were used to investigate the mechanisms underlying the progression of VSMCs phenotypic transformation, proliferation and migration. Increased TRIM65 expression was detected in α-SMA-positive cells in the medial and atherosclerotic lesions of autopsy specimens. TRIM65 overexpression increased, whereas genetic knockdown of TRIM65 remarkably inhibited, atherosclerotic plaque development. Mechanistically, TRIM65 overexpression activated PI3K/Akt/mTOR signaling, resulting in the loss of the VSMCs contractile phenotype, including calponin, α-SMA, and SM22α, as well as cell proliferation and migration. However, opposite phenomena were observed when TRIM65 was deficient in vivo or in vitro. Moreover, in cultured PDGF-BB-induced TRIM65-overexpressing VSMCs, inhibition of PI3K by treatment with the inhibitor LY-294002 for 24 h markedly attenuated PI3K/Akt/mTOR activation, regained the VSMCs contractile phenotype, and blocked the progression of cell proliferation and migration. CONCLUSIONS: TRIM65 overexpression enhances atherosclerosis development by promoting phenotypic transformation of VSMCs from contractile to synthetic state through activation of the PI3K/Akt/mTOR signal pathway.

The role of CoQ10 in embryonic development.

Coenzyme Q10 (CoQ10) is a natural component widely present in the inner membrane of mitochondria. CoQ10 functions as a key cofactor for adenosine triphosphate (ATP) production and exhibits antioxidant properties in vivo. Mitochondria, as the energy supply center of cells, play a crucial role in germ cell maturation and embryonic development, a complicated process of cell division and cellular differentiation that transforms from a single cell (zygote) to a multicellular organism (fetus). Here, we discuss the effects of CoQ10 on oocyte maturation and the important role of CoQ10 in the growth of various organs during different stages of fetal development. These allowed us to gain a deeper understanding of the pathophysiology of embryonic development and the potential role of CoQ10 in improving fertility quality. They also provide a reference for further developing its application in clinical treatments.

"MD" method for the precise analysis of the O-acetyl-mannan structure and disclosure of the role in the conformational stability of insulin.

Among the diversified glycan modifications, acylation is one of the most abundant. This modification could be responsible for many of the properties of glycans, such as structural stability and specificity for biological activity. To obtain better insight into the effects of acetylation of glycans on the structure and thermostability of insulin, it is critical to investigate glycans with a high degree of acetylation. An in-depth study of three functional glycans named acetyl-mannan from Dendrobium devonianum (DDAM) was conducted herein by efficient enzymatic depolymerization, and the effect of glycosidic bonds on acetylation modification sites was studied through a molecular dynamics (MD) method, as well as its positive effect on insulin secretion, glucose uptake, and the thermal stability of tertiary structures in vitro. Further study indicated that DDAMs play a hypoglycemic role by sparking the thermostability of the insulin conformation. The hypoglycemic activity displayed a positive correlation with the degree of acetylation in DDAMs. In this work, through the MD method, we confirmed the structure characteristics of DDAMs and provided accurate data support for the structure-activity relationship analysis. Thus, these findings demonstrated that DDAMs might be an exceptional leading compound for the stability of insulin drug.