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1.
Regen Ther ; 26: 308-314, 2024 Jun.
Article in English | MEDLINE | ID: mdl-39022599

ABSTRACT

Background: Skin defects caused by open hand trauma are difficult to treat clinically and severely affect the recovery of hand function. Autologous platelet-rich plasma (PRP) has been widely used in the treatment of refractory chronic wounds, but its use in hand trauma skin defects remains scarce. Methods: This study compared the outcomes of 27 patients treated with PRP to 31 patients undergoing skin flap transplantation for hand wounds. We assessed several parameters, including healing times, duration of surgery, postoperative pain (VAS score), intraoperative amputation length, finger function, sensation restoration, nail bed preservation, and hospitalization expenses. Results: PRP-treated patients showed a mean healing time of 21.59 ± 3.17 days. Surgical times were significantly shorter in the PRP group (22.04 ± 7.04 min) compared to the flap group (57.45 ± 8.15 min, P < 0.0001). PRP patients experienced longer postoperative healing times (20.15 ± 2.16 days) than those in the skin flap group (12.84 ± 1.08 days, P < 0.0001), but reported lower pain scores (1.3 ± 1.44 vs 2.55 ± 2.06, P = 0.0119). Range of Motion (ROM) at the proximal interphalangeal joint was better in the PRP group (96.26° ± 6.69) compared to the flap group (86.16° ± 15.24, P = 0.0028). Sensory outcomes favored the PRP group, with a two-point discrimination of 2.37 ± 1.34 mm versus 2.52 ± 1.27 mm in the flap group (P = 0.0274). Costs were lower in the PRP group ($2081.6 ± 258.14 vs $2680.18 ± 481.15, P < 0.0001). Conclusion: PRP treatment for skin defects from hand trauma is effective, offering advantages in terms of reduced surgical time, pain, and cost, with comparable or superior functional outcomes to flap transplantation. Despite longer healing times, PRP may represent a preferable option for open hand injuries, preserving more nail beds and resulting in better sensation and joint motion.

2.
Commun Biol ; 7(1): 795, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38951640

ABSTRACT

The peroxisome is a versatile organelle that performs diverse metabolic functions. PEX3, a critical regulator of the peroxisome, participates in various biological processes associated with the peroxisome. Whether PEX3 is involved in peroxisome-related redox homeostasis and myocardial regenerative repair remains elusive. We investigate that cardiomyocyte-specific PEX3 knockout (Pex3-KO) results in an imbalance of redox homeostasis and disrupts the endogenous proliferation/development at different times and spatial locations. Using Pex3-KO mice and myocardium-targeted intervention approaches, the effects of PEX3 on myocardial regenerative repair during both physiological and pathological stages are explored. Mechanistically, lipid metabolomics reveals that PEX3 promotes myocardial regenerative repair by affecting plasmalogen metabolism. Further, we find that PEX3-regulated plasmalogen activates the AKT/GSK3ß signaling pathway via the plasma membrane localization of ITGB3. Our study indicates that PEX3 may represent a novel therapeutic target for myocardial regenerative repair following injury.


Subject(s)
Cell Membrane , Integrin beta3 , Mice, Knockout , Regeneration , Animals , Mice , Integrin beta3/metabolism , Integrin beta3/genetics , Cell Membrane/metabolism , Myocytes, Cardiac/metabolism , Male , Plasmalogens/metabolism , Signal Transduction , Myocardium/metabolism , Myocardium/pathology , Mice, Inbred C57BL , Heart Injuries/metabolism , Heart Injuries/pathology , Heart Injuries/genetics , Cell Proliferation , Membrane Proteins/metabolism , Membrane Proteins/genetics
3.
Angew Chem Int Ed Engl ; : e202410179, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38953224

ABSTRACT

Photocatalytic synthesis of H2O2 is an advantageous and ecologically sustainable alternative to the conventional anthraquinone process. However, achieving high conversion efficiency without sacrificial agents remains a challenge. In this study, two covalent organic frameworks (COF-O and COF-C) were prepared with identical skeletal structures but with their pore walls anchored to different alkyl chains. They were used to investigate the effect of the chemical microenvironment of pores on photocatalytic H2O2 production. Experimental results reveal a change of hydrophilicity in COF-O, leading to suppressed charge recombination, diminished charge transfer resistance, and accelerated interfacial electron transfer. An apparent quantum yield as high as 10.3% (λ = 420 nm) can be achieved with H2O and O2 through oxygen reduction reaction. This is among the highest ever reported for polymer photocatalysts. This study may provide a novel avenue for optimizing photocatalytic activity and selectivity in H2O2 generation.

4.
Comput Biol Med ; 179: 108901, 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-39029429

ABSTRACT

BACKGROUND: Dilated cardiomyopathy (DCM) is a common cause of heart failure. However, the role of cellular senescence in DCM has not been fully elucidated. Here, we aimed to investigate senescence in DCM, identify senescence related characteristic genes, and explore the potential small molecule compounds for DCM treatment. METHODS: DCM-associated datasets and senescence-related genes were respectively obtained from Gene Expression Omnibus (GEO) database and CellAge database. The characteristic genes were identified through methods including weighted gene co-expression network analysis (WGCNA), least absolute shrinkage and selection operator (LASSO), and random forest. The expression of characteristic genes was verified in the mouse DCM model. Moreover, the CIBERSORT algorithm was applied to analyze immune characteristics of DCM. Finally, several therapeutic compounds were predicted by CMap analysis, and the potential mechanism of chlorogenic acid (CGA) was investigated by molecular docking and molecular dynamics simulation. RESULTS: Three DCM- and senescence-related characteristic genes (MME, GNMT and PLA2G2A) were ultimately identified through comprehensive transcriptome analysis, and were experimentally verified in the doxorubicin induced mouse DCM. Meanwhile, the established diagnostic model, derived from dataset analysis, showed ideal diagnostic performance for DCM. Immune cell infiltration analysis suggested dysregulation of inflammation in DCM, and the characteristic genes were significantly associated with invasive immune cells. Finally, based on the specific gene expression profile of DCM, several potential therapeutic compounds were predicted through CMap analysis. In addition, molecular docking and molecular dynamics simulations suggested that CGA could bind to the active pocket of MME protein. CONCLUSION: Our study presents three characteristic genes (MME, PLA2G2A, and GNMT) and a novel senescence-based diagnostic nomogram, and discusses potential therapeutic compounds, providing new insights into the diagnosis and treatment of DCM.

5.
Biochem Pharmacol ; 226: 116337, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38844265

ABSTRACT

Spinal cystic echinococcosis (CE) is a rare but malignant zoonosis that can cause disability or even death in more than half of patients. Due to the complex pathological features, it is not curable by conventional drugs and surgery, so new therapeutic targets urgently need to be discovered. In this study, we clarify the occurrence of the phenomenon of spinal encapsulation angiogenesis and explore its underlying molecular mechanisms. A co-culture system was established by protoscoleces (PSCs) with human umbilical vein endothelial cells (HUVECs) which showed a high expression level of Nrf2. A short hairpin RNA (shRNA) and Sulforaphane (SFN) affecting the expression of Nrf2 were used to treat HUVECs. The results showed that Nrf2 could promote the tube formation of HUVECs. Nrf2 also exerts a protective effect against HUVECs, which is achieved by promoting NQO1 expression to stabilize ROS levels. Furthermore, autophagy activation significantly promotes angiogenesis in the spinal echinococcosis model (SEM) as a result of Nrf2 regulation of oxidative stress. These results suggest that the ROS/Nrf2/autophagy axis can induce angiogenesis and may be a potential target for the treatment of spinal cystic echinococcosis.

6.
J Am Heart Assoc ; 13(13): e034805, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38934866

ABSTRACT

BACKGROUND: The regenerative capacity of the adult mammalian hearts is limited. Numerous studies have explored mechanisms of adult cardiomyocyte cell-cycle withdrawal. This translational study evaluated the effects and underlying mechanism of rhCHK1 (recombinant human checkpoint kinase 1) on the survival and proliferation of cardiomyocyte and myocardial repair after ischemia/reperfusion injury in swine. METHODS AND RESULTS: Intramyocardial injection of rhCHK1 protein (1 mg/kg) encapsulated in hydrogel stimulated cardiomyocyte proliferation and reduced cardiac inflammation response at 3 days after ischemia/reperfusion injury, improved cardiac function and attenuated ventricular remodeling, and reduced the infarct area at 28 days after ischemia/reperfusion injury. Mechanistically, multiomics sequencing analysis demonstrated enrichment of glycolysis and mTOR (mammalian target of rapamycin) pathways after rhCHK1 treatment. Co-Immunoprecipitation (Co-IP) experiments and protein docking prediction showed that CHK1 (checkpoint kinase 1) directly bound to and activated the Serine 37 (S37) and Tyrosine 105 (Y105) sites of PKM2 (pyruvate kinase isoform M2) to promote metabolic reprogramming. We further constructed plasmids that knocked out different CHK1 and PKM2 amino acid domains and transfected them into Human Embryonic Kidney 293T (HEK293T) cells for CO-IP experiments. Results showed that the 1-265 domain of CHK1 directly binds to the 157-400 amino acids of PKM2. Furthermore, hiPSC-CM (human iPS cell-derived cardiomyocyte) in vitro and in vivo experiments both demonstrated that CHK1 stimulated cardiomyocytes renewal and cardiac repair by activating PKM2 C-domain-mediated cardiac metabolic reprogramming. CONCLUSIONS: This study demonstrates that the 1-265 amino acid domain of CHK1 binds to the 157-400 domain of PKM2 and activates PKM2-mediated metabolic reprogramming to promote cardiomyocyte proliferation and myocardial repair after ischemia/reperfusion injury in adult pigs.


Subject(s)
Cell Proliferation , Checkpoint Kinase 1 , Disease Models, Animal , Myocardial Reperfusion Injury , Myocytes, Cardiac , Animals , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/pathology , Myocardial Reperfusion Injury/metabolism , Myocardial Reperfusion Injury/pathology , Myocardial Reperfusion Injury/enzymology , Myocardial Reperfusion Injury/genetics , Checkpoint Kinase 1/metabolism , Checkpoint Kinase 1/genetics , Humans , Pyruvate Kinase/metabolism , Pyruvate Kinase/genetics , HEK293 Cells , Swine , Cellular Reprogramming , Thyroid Hormone-Binding Proteins , Regeneration , Protein Binding , Sus scrofa , Ventricular Remodeling/physiology , Recombinant Proteins/metabolism , Recombinant Proteins/pharmacology , Energy Metabolism/drug effects , Thyroid Hormones/metabolism , Metabolic Reprogramming
8.
Int J Cardiol Cardiovasc Risk Prev ; 21: 200286, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38813099

ABSTRACT

Background: Ventricular arrhythmias (VAs) mainly occur in the early post-myocardial infarction (MI) period. However, studies examining the association between total myocardial ischemia time interval and the risk of new-onset VAs during a long-term follow-up are scarce. Methods: This study (symptom-to-balloon time and VEntricular aRrhYthmias in patients with STEMI, VERY-STEMI study) was a multicenter, observational cohort and real-world study, which included patients with ST-segment elevation MI (STEMI) undergoing percutaneous coronary intervention (PCI). The primary endpoint was cumulative new-onset VAs during follow-up. The secondary endpoints were the major adverse cardiovascular events (MACE) and changes in left ventricular ejection fraction (ΔLVEF, %). Results: A total of 517 patients with STEMI were included and 236 primary endpoint events occurred. After multivariable adjustments, compared to patients with S2BT of 24 h-7d, those with S2BT ≤ 24 h and S2BT > 7d had a lower risk of primary endpoint. RCS showed an inverted U-shaped relationship between S2BT and the primary endpoint, with an S2BT of 68.4 h at the inflection point. Patients with S2BT ≤ 24 h were associated with a lower risk of MACE and a 4.44 increase in LVEF, while there was no significant difference in MACE and LVEF change between the S2BT > 7d group and S2BT of 24 h-7d group. Conclusions: S2BT of 24 h-7d in STEMI patients was associated with a higher risk of VAs during follow-up. There was an inverted U-shaped relationship between S2BT and VAs, with the highest risk at an S2BT of 68.4 h.

9.
Eur J Med Chem ; 272: 116458, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38703557

ABSTRACT

Microtubules are recognized as one of the most vital and attractive targets in anticancer therapy. The development of novel tubulin-targeting agents with a new action mechanism is imperative. Based on the hydrophobic tagging strategy, the molecular scaffold of tirbanibulin was selected as tubulin target-binding moiety, subsequent to which a series of target compounds were rationally designed by selecting various combinations of linkers and hydrophobic tags. A set of novel molecules were synthesized and most of them exhibited potent antiproliferative activity against tumor cells in vitro. The most active compound 14b inhibited polymerization of purified recombinant tubulin and induced degradation of α- and ß-tubulin in MCF-7 cells. Notably, following treatment with compound 14b, an unexpected phenomenon of "microtubules fragmentation" was observed via immunofluorescence staining. Furthermore, compound 14b possessed antitumor activity in the 4T1 allograft models with TGI of 74.27 % without significant toxicity. In this work, we report the discovery of novel dual-mechanism tubulin-targeting agents.


Subject(s)
Antineoplastic Agents , Cell Proliferation , Drug Design , Drug Screening Assays, Antitumor , Polymerization , Tubulin Modulators , Tubulin , Humans , Tubulin/metabolism , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Tubulin Modulators/pharmacology , Tubulin Modulators/chemical synthesis , Tubulin Modulators/chemistry , Polymerization/drug effects , Cell Proliferation/drug effects , Structure-Activity Relationship , Molecular Structure , Animals , Dose-Response Relationship, Drug , Proteolysis/drug effects , Mice , Cell Line, Tumor , MCF-7 Cells , Female
10.
ChemSusChem ; : e202400528, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38716782

ABSTRACT

Hydrogen peroxide (H2O2) plays a crucial role in various applications, such as green oxidation processes and the production of high-quality fuels. Currently, H2O2 is primarily manufactured using the indirect anthraquinone method, known for its significant energy consumption and the generation of intensive by-products. Extensive research has been conducted on the photocatalytic production of H2O2 via oxygen reduction reaction (ORR), with polymeric carbon nitride (PCN) emerging as a promising catalyst for this conversion. This review article is organized around two approaches. The first part main consists of the chemical optimization of the PCN structure, while the second focuses on the physical integration of PCN with other functional materials. The objective is to clarify the correlation between the physicochemical properties of PCN photocatalysts and their effectiveness in H2O2 production. Through a thorough review and analysis of the findings, this article seeks to stimulate new insights and achievements, not only in the domain of H2O2 production via ORR but also in other redox reactions.

11.
ACS Cent Sci ; 10(3): 658-665, 2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38559285

ABSTRACT

The Tafel slope represents a critical kinetic parameter for mechanistic studies of electrochemical reactions, including the hydrogen evolution reaction (HER). Linear fitting of the polarization curve in a N2-saturated electrolyte is commonly used to determine Tafel slopes, which is, however, frequently plagued with inconsistencies. Our systematic studies reveal that the Tafel slopes derived from this approach are loading- and potential-dependent, and could substantially exceed the theoretical limits. Our analyses indicate that this discrepancy is largely attributed to the locally trapped HER-generated H2 in the catalyst layer. A non-negligible hydrogen oxidation reaction (HOR) current more prominently offsets the HER current at the smaller HER overpotential regime, resulting in an artificially smaller Tafel slope. On the other hand, at the higher overpotential where the HOR current becomes negligible, the locally trapped H2 substantially suppresses further HER current growth, leading to an artificially larger Tafel slope. The Butler-Volmer method accounts for both the HER and HOR currents in the fitting, which offers a more reliable method for pure Pt catalysts but is less applicable to transition-metal decorated Pt surfaces with distinct HER/HOR kinetics. Our studies underscore the challenges in Tafel slope analysis and the need for strict controls for reliable comparisons among different catalyst systems.

12.
Cell Metab ; 2024 Mar 28.
Article in English | MEDLINE | ID: mdl-38569557

ABSTRACT

Activating Nrf2 by small molecules is a promising strategy to treat postmenopausal osteoporosis. However, there is currently no Nrf2 activator approved for treating chronic diseases, and the downstream mechanism underlying the regulation of Nrf2 on osteoclast differentiation remains unclear. Here, we found that bitopertin, a clinical-stage glycine uptake inhibitor, suppresses osteoclast differentiation and ameliorates ovariectomy-induced bone loss by activating Nrf2. Mechanistically, bitopertin interacts with the Keap1 Kelch domain and decreases Keap1-Nrf2 binding, leading to reduced Nrf2 ubiquitination and degradation. Bitopertin is associated with less adverse events than clinically approved Nrf2 activators in both mice and human subjects. Furthermore, Nrf2 transcriptionally activates ferroportin-coding gene Slc40a1 to reduce intracellular iron levels in osteoclasts. Loss of Nrf2 or iron supplementation upregulates ornithine-metabolizing enzyme Odc1, which decreases ornithine levels and thereby promotes osteoclast differentiation. Collectively, our findings identify a novel clinical-stage Nrf2 activator and propose a novel Nrf2-iron-ornithine metabolic axis in osteoclasts.

13.
Proc Natl Acad Sci U S A ; 121(18): e2319751121, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38662548

ABSTRACT

Defect engineering has been widely applied in semiconductors to improve photocatalytic properties by altering the surface structures. This study is about the transformation of inactive WO3 nanosheets to a highly effective CO2-to-CH4 conversion photocatalyst by introducing surface-ordered defects in abundance. The nonstoichiometric WO3-x samples were examined by using aberration-corrected electron microscopy. Results unveil abundant surface-ordered terminations derived from the periodic {013} stacking faults with a defect density of 20.2%. The {002} surface-ordered line defects are the active sites for fixation CO2, transforming the inactive WO3 nanosheets into a highly active catalyst (CH4: O2 = 8.2: 16.7 µmol h-1). We believe that the formation of the W-O-C-W-O species is a critical step in the catalytic pathways. This work provides an atomic-level comprehension of the structural defects of catalysts for activating small molecules.

14.
Small ; : e2402004, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38686672

ABSTRACT

The selective conversion of ethane (C2H6) to ethylene (C2H4) under mild conditions is highly wanted, yet very challenging. Herein, it is demonstrated that a Pt/WO3-x catalyst, constructed by supporting ultrafine Pt nanoparticles on the surface of oxygen-deficient tungsten oxide (WO3-x) nanoplates, is efficient and reusable for photocatalytic C2H6 dehydrogenation to produce C2H4 with high selectivity. Specifically, under pure light irradiation, the optimized Pt/WO3-x photocatalyst exhibits C2H4 and H2 yield rates of 291.8 and 373.4 µmol g-1 h-1, respectively, coupled with a small formation of CO (85.2 µmol g-1 h-1) and CH4 (19.0 µmol g-1 h-1), corresponding to a high C2H4 selectivity of 84.9%. Experimental and theoretical studies reveal that the vacancy-rich WO3-x catalyst enables broad optical harvesting to generate charge carriers by light for working the redox reactions. Meanwhile, the Pt cocatalyst reinforces adsorption of C2H6, desorption of key reaction species, and separation and migration of light-induced charges to promote the dehydrogenation reaction with high productivity and selectivity. In situ diffuse reflectance infrared Fourier transform spectroscopy and density functional theory calculation expose the key intermediates formed on the Pt/WO3-x catalyst during the reaction, which permits the construction of the possible C2H6 dehydrogenation mechanism.

15.
J Orthop Surg Res ; 19(1): 245, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38627743

ABSTRACT

PURPOSE: The objective of this study was to examine the predictive value of a newly developed MRI-based Endplate Bone Quality (EBQ) in relation to the development of cage subsidence following anterior cervical discectomy and fusion (ACDF). METHODS: Patients undergoing ACDF for degenerative cervical diseases between January 2017 and June 2022 were included. Correlation between EBQ scores and segmental height loss was analyzed using Pearson's correlation. ROC analyses were employed to ascertain the EBQ cut-off values that predict the occurrence of cage subsidence. Multivariate logistic regression analyses were conducted to identify the risk factors associated with postoperative cage subsidence. RESULTS: 23 individuals (14.56%) exhibited the cage subsidence after ACDF. In the nonsubsidence group, the average EBQ and lowest T-score were determined to be 4.13 ± 1.14 and - 0.84 ± 1.38 g/cm2 respectively. In contrast, the subsidence group exhibited a mean EBQ and lowest T-score of 5.38 ± 0.47 (p < 0.001) and - 1.62 ± 1.34 g/cm2 (p = 0.014), respectively. There was a significant positive correlation (r = 0.798**) between EBQ and the segmental height loss. The EBQ threshold of 4.70 yielded optimal sensitivity (73.9%) and specificity (93.3%) with AUC of 0.806. Furthermore, the lowest T-score (p = 0.045, OR 0.667) and an elevated cervical EBQ score (p < 0.001, OR 8.385) were identified as significant risk factors for cage subsidence after ACDF. CONCLUSIONS: The EBQ method presents itself as a promising and efficient tool for surgeons to assess patients at risk of cage subsidence and osteoporosis prior to cervical spine surgery, utilizing readily accessible patient data.


Subject(s)
Cervical Vertebrae , Spinal Fusion , Humans , Cervical Vertebrae/diagnostic imaging , Cervical Vertebrae/surgery , Retrospective Studies , Magnetic Resonance Imaging , Neck/surgery , Diskectomy/adverse effects , Diskectomy/methods , Spinal Fusion/adverse effects , Spinal Fusion/methods , Treatment Outcome
16.
Adv Mater ; 36(26): e2313209, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38591644

ABSTRACT

Metal nanoparticle (NP) cocatalysts are widely investigated for their ability to enhance the performance of photocatalytic materials; however, their practical application is often limited by the inherent instability under light irradiation. This challenge has catalyzed interest in exploring high-entropy alloys (HEAs), which, with their increased entropy and lower Gibbs free energy, provide superior stability. In this study, 3.5 nm-sized noble-metal-free NPs composed of a FeCoNiCuMn HEA are successfully synthesized. With theoretic calculation and experiments, the electronic structure of HEA in augmenting the catalytic CO2 reduction has been uncovered, including the individual roles of each element and the collective synergistic effects. Then, their photocatalytic CO2 reduction capabilities are investigated when immobilized on TiO2. HEA NPs significantly enhance the CO2 photoreduction, achieving a 23-fold increase over pristine TiO2, with CO and CH4 production rates of 235.2 and 19.9 µmol g-1 h-1, respectively. Meanwhile, HEA NPs show excellent stability under simulated solar irradiation, as well high-energy X-ray irradiation. This research emphasizes the promising role of HEA NPs, composed of earth-abundant elements, in revolutionizing the field of photocatalysis.

17.
Insects ; 15(3)2024 Feb 21.
Article in English | MEDLINE | ID: mdl-38535338

ABSTRACT

Trehalose is an important carbohydrate substance in insect hemolymph. Chitin is the main component of cuticle and peritrophic matrix in insects. Trehalase (Tre) catalyzes the decomposition of trehalose. Few studies of trehalase in lepidopteran insects have been conducted. Here, the functions of soluble Tre (Tre1) and membrane-bound Tre (Tre2) in the growth and development of Mythimna separata were investigated. We cloned and identified Tre1 and Tre2 cDNA sequences in M. separata. Analysis expression revealed that MsTre1 and MsTre2 were highly expressed in midgut and integument, respectively. The expression of MsTre1 and MsTre2 was highest in the pupal stage. We used RNA interference (RNAi) to inhibit Tre expression in M. separata larvae. Injection of dsMsTre1 or dsMsTre2 resulted in abnormal phenotypes and impeded normal molting. Silencing of MsTre1 and MsTre2 resulted in significant changes in the expression of genes in the trehalose and chitin metabolism pathways, significantly increased the trehalose and glycogen content, and significantly decreased MsTre1 and MsTre2 activity, the glucose content, and the chitin content in midgut and integument. Silencing of MsTre1 slowed larval molting, and the new cuticle was significantly thinner. These results indicate that RNAi of Tre may be useful for control strategies against M. separata.

18.
Indian J Orthop ; 58(3): 242-249, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38425821

ABSTRACT

Introduction: We present a new surgical technique of Krackow suture combined with vertical Nice knot for the treatment of inferior patellar fractures and report the clinical results. Patients and Methods: Seventeen consecutive patients admitted with inferior patellar fractures over a 2-year period from June 2019 to February 2022 were prospectively enrolled. The AO classification was 34-A1. All patients underwent open reduction and fixation with Krackow sutures in combination with vertical Nice knot. Postoperative follow-up was performed for at least 1 year to evaluate knee function. Results: The mean age of seventeen patients was 53.2 ± 9.5 years (39-68 years), and all patients were followed up for more than 12 months. The operation time was 54.6 ± 7.7 min (42-68 min). No patients had nonunion, joint stiffness, and joint pain. All cases achieved bony union at an average of 9.9 ± 1.5 weeks (8-13 weeks) after surgery. At the last follow-up, there was no significant difference in range of motion between the injured knee (129.7 ± 3.3°, range 125-135°) and the unaffected knee (130.8 ± 3.8°, range 126-137°) (t = 0.28, P > 0.05). The mean Bostman score of the knee joint was 29.6 ± 0.7, including 15 excellent cases (88.2%) and two good case (11.8%). Conclusion: Krackow sutures combined with vertical Nice knots are stable and reliable in the treatment of inferior patellar fractures. Knee rehabilitation can be performed immediately after surgery and satisfactory knee function can be achieved. It is a safe, simple, and reliable alternative surgical method, and patients do not need to bear the secondary surgical injury of removing the internal fixation material. Therefore, it is suitable for the application of clinical promotion. Supplementary Information: The online version contains supplementary material available at 10.1007/s43465-023-01093-0.

19.
J Mol Cell Cardiol ; 189: 66-82, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38432502

ABSTRACT

The regenerative capacity of the adult mammalian heart is limited, while the neonatal heart is an organ with regenerative and proliferative ability. Activating adult cardiomyocytes (CMs) to re-enter the cell cycle is an effective therapeutic method for ischemic heart disease such as myocardial infarction (MI) and heart failure. Here, we aimed to reveal the role and potential mechanisms of cellular nucleic acid binding protein (CNBP) in cardiac regeneration and repair after heart injury. CNBP is highly expressed within 7 days post-birth while decreases significantly with the loss of regenerative ability. In vitro, overexpression of CNBP promoted CM proliferation and survival, whereas knockdown of CNBP inhibited these processes. In vivo, knockdown of CNBP in CMs robustly hindered myocardial regeneration after apical resection in neonatal mice. In adult MI mice, CM-specific CNBP overexpression in the infarct border zone ameliorated myocardial injury in acute stage and facilitated CM proliferation and functional recovery in the long term. Quantitative proteomic analysis with TMT labeling showed that CNBP overexpression promoted the DNA replication, cell cycle progression, and cell division. Mechanically, CNBP overexpression increased the expression of ß-catenin and its downstream target genes CCND1 and c-myc; Furthermore, Luciferase reporter and Chromatin immunoprecipitation (ChIP) assays showed that CNBP could directly bind to the ß-catenin promoter and promote its transcription. CNBP also upregulated the expression of G1/S-related cell cycle genes CCNE1, CDK2, and CDK4. Collectively, our study reveals the positive role of CNBP in promoting cardiac repair after injury, providing a new therapeutic option for the treatment of MI.


Subject(s)
Heart , Myocytes, Cardiac , RNA-Binding Proteins , Animals , Mice , beta Catenin/genetics , beta Catenin/metabolism , Cell Proliferation , Mammals/metabolism , Myocardial Infarction/metabolism , Myocytes, Cardiac/metabolism , Nucleic Acids/metabolism , Proteomics , Transcription Factors/metabolism , RNA-Binding Proteins/metabolism , Signal Transduction , Regeneration , Heart/physiology
20.
J Am Chem Soc ; 146(14): 9623-9630, 2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38533830

ABSTRACT

The fundamental understanding of sluggish hydrogen evolution reaction (HER) kinetics on a platinum (Pt) surface in alkaline media is a topic of considerable debate. Herein, we combine cyclic voltammetry (CV) and electrical transport spectroscopy (ETS) approaches to probe the Pt surface at different pH values and develop molecular-level insights into the pH-dependent HER kinetics in alkaline media. The change in HER Tafel slope from ∼110 mV/decade in pH 7-10 to ∼53 mV/decade in pH 11-13 suggests considerably enhanced kinetics at higher pH. The ETS studies reveal a similar pH-dependent switch in the ETS conductance signal at around pH 10, suggesting a notable change of surface adsorbates. Fixed-potential calculations and chemical bonding analysis suggest that this switch is attributed to a change in interfacial water orientation, shifting from primarily an O-down configuration below pH 10 to a H-down configuration above pH 10. This reorientation weakens the O-H bond in the interfacial water molecules and modifies the reaction pathway, leading to considerably accelerated HER kinetics at higher pH. Our integrated studies provide an unprecedented molecular-level understanding of the nontrivial pH-dependent HER kinetics in alkaline media.

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