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1.
Heliyon ; 10(11): e31390, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38832262

ABSTRACT

Background: Weightlifting exposes athletes to significant loads, potentially placing the knee joint in an abnormal mechanical environment and leading to anterior cruciate ligament (ACL) injuries. Once an ACL injury occurs, it can affect athletes' competitive ability to varying degrees and even prematurely end their career. Understanding the biomechanical mechanisms of ACL injuries in weightlifters helps in comprehensively understanding the stress patterns and degrees on ACL during human movement, and identifying potential injury-causing factors, thereby enabling the implementation of appropriate preventive measures to reduce the occurrence of injuries. This study aimed to explore the biomechanical mechanisms of ACL injuries during the jerk dip phase of clean and jerk in weightlifters, providing a theoretical basis for the prevention of ACL injuries in weightlifting sports. Methods: This study utilized the German SIMI Motion 10.2 movement analysis system and the AnyBody simulation system to analyze the kinematic and dynamic parameters of a 109 kg + class weightlifter (height: 191 cm, age: 22 years, weight: 148 kg, athletic level: elite) performing a 205 kg clean and jerk (non-injured) and a 210 kg clean and jerk (ACL injury occurred). The differences in kinematic and dynamic indicators of lower limb joints under injured and non-injured jerk dip conditions were investigated. Results: Knee joint torque during non-injured clean and jerk was consistently positive (i.e., external rotation) but turned from positive to negative (i.e., from external rotation to internal rotation) during injured clean and jerk and reached a maximum internal rotation torque of 21.34 Nm at the moment of injury. At every moment, the muscle activation and simulated muscle force of the quadriceps and gastrocnemius during the injured clean and jerk were higher than those during the non-injured clean and jerk. By contrast, the muscle activation and simulated muscle force of the semitendinosus, semimembranosus, biceps femoris, and soleus during non-injured clean and jerk were higher than those during injured clean and jerk. The knee joint internal rotation angle during injured clean and jerk first increased and then declined, reaching a peak at 46.93° at the moment of injury, whereas it gradually increased during non-injured clean and jerk. The proximal tibia on the left side during the injured clean and jerk moved forward faster by 0.76 m/s compared with that during the non-injured clean and jerk. Conclusions: The small muscle activation and simulated muscle force of the hamstring and soleus could not resist timely and effectively the large muscle activation and simulated muscle force of the quadriceps (especially the medial quad) and gastrocnemius. As such, the force applied to the ACL could exceed its ultimate load-bearing capacity. Kinematic indicators in the athlete's injured lift demonstrated certain disparities from those in their non-injured lift. Knee internal rotation and tibial anterior translation during the jerk dip phase of weightlifting might be the kinematic characteristics of ACL injuries.

2.
Anal Chim Acta ; 1306: 342581, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38692785

ABSTRACT

Cancer detection is still a major challenge in public health. Identification of oncogene is the first step toward solving this problem. Studies have revealed that various cancers are associated with miRNA expression. Therefore, the sensitive detection of miRNA is substantially important to solve the cancer problem. In this study, let-7a, a representative substance of miRNA, was selected as the detection target. With the assistance of magnetic beads commonly used in biosensors and self-synthesized graphene oxide materials, specificity and sensitivity detection of the target gene let-7a were achieved via protease-free signal amplification. The limit of detection (LOD) was as low as 15.015pM. The fluorescence signal intensity showed a good linear relationship with the logarithm of let-7a concentration. The biosensor could also detect let-7a in complex human serum samples. Overall, this fluorescent biosensor is not only simple to operate, but also strongly specificity to detect let-7a. Therefore, it has substantial potential for application in the early diagnosis of clinical medicine and biological research.


Subject(s)
Biosensing Techniques , Graphite , Limit of Detection , MicroRNAs , Biosensing Techniques/methods , Humans , Graphite/chemistry , MicroRNAs/analysis , MicroRNAs/blood , Spectrometry, Fluorescence , Fluorescent Dyes/chemistry , Neoplasms/diagnosis , Neoplasms/blood
3.
Prog Nucl Magn Reson Spectrosc ; 140-141: 1-41, 2024.
Article in English | MEDLINE | ID: mdl-38705634

ABSTRACT

Solid-state NMR spectroscopy (ssNMR) can provide details about the structure, host-guest/guest-guest interactions and dynamic behavior of materials at atomic length scales. A crucial use of ssNMR is for the characterization of zeolite catalysts that are extensively employed in industrial catalytic processes. This review aims to spotlight the recent advancements in ssNMR spectroscopy and its application to zeolite chemistry. We first review the current ssNMR methods and techniques that are relevant to characterize zeolite catalysts, including advanced multinuclear and multidimensional experiments, in situ NMR techniques and hyperpolarization methods. Of these, the methodology development on half-integer quadrupolar nuclei is emphasized, which represent about two-thirds of stable NMR-active nuclei and are widely present in catalytic materials. Subsequently, we introduce the recent progress in understanding zeolite chemistry with the aid of these ssNMR methods and techniques, with a specific focus on the investigation of zeolite framework structures, zeolite crystallization mechanisms, surface active/acidic sites, host-guest/guest-guest interactions, and catalytic reaction mechanisms.

4.
BMC Gastroenterol ; 24(1): 155, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38714955

ABSTRACT

BACKGROUND: Antiplatelet and anticoagulation drugs complicate acute gastrointestinal bleeding (GIB) patients. Limited data about the risk factors and patient management has been presented. This study explored the association between previous antiplatelet or anticoagulant drug usage and clinical outcomes in GIB patients to improve awareness further and optimize treatment. METHODS: We conducted a multicenter, non-interventional, real-world prospective study in 106 hospitals in 23 provinces in China. GIB patients confirmed in the emergency department were included and were grouped according to previous drug histories. Univariate analysis, multivariate logistic regression, and multivariate stratification models were performed separately to investigate the associations. RESULTS: A total of 2299 patients (57.23 ± 17.21 years old, 68.3% male) were included, of whom 20.1% and 2.9% received antiplatelet and anticoagulation therapy, respectively. The all-cause 28-day mortality rates in patients without antiplatelet or anticoagulants, patients undergoing antiplatelet treatment, and patients with anticoagulation therapy were 2.8%, 4.6%, and 10.5%, respectively. After adjusting for confounding factors, both antiplatelet [odd ratio (OR), 2.92; 95% confidence interval (CI), 1.48-5.76; p = 0.002] and anticoagulation therapy (OR, 8.87; 95% CI, 3.02-26.02; p < 0.001) were associated with higher 28-day mortality. In the subgroup analysis, blood transfusion, especially red blood cell transfusion, in patients undergoing antiplatelet and anticoagulation therapy was associated with a decreased death risk. CONCLUSION: We confirmed an association between concurrent antiplatelet or anticoagulation therapy in GIB patients and elevated 28-day mortality. Blood transfusions could improve poor outcomes in such patients.


Subject(s)
Anticoagulants , Gastrointestinal Hemorrhage , Platelet Aggregation Inhibitors , Humans , Gastrointestinal Hemorrhage/chemically induced , Gastrointestinal Hemorrhage/therapy , Gastrointestinal Hemorrhage/mortality , Platelet Aggregation Inhibitors/adverse effects , Platelet Aggregation Inhibitors/therapeutic use , Male , Middle Aged , Female , Anticoagulants/adverse effects , Anticoagulants/therapeutic use , Prospective Studies , Risk Factors , Aged , China/epidemiology , Adult
6.
Materials (Basel) ; 17(9)2024 May 03.
Article in English | MEDLINE | ID: mdl-38730953

ABSTRACT

In this article, ABA triblock copolymer (tri-BCP) thermoplastic elastomers with poly(ethylene oxide) (PEO) middle block and polyzwitterionic poly(4-vinylpyridine) propane-1-sulfonate (PVPS) outer blocks were synthesized. The PVPS-b-PEO-b-PVPS tri-BCPs were doped with lithium bis-(trifluoromethane-sulfonyl) imide (LiTFSI) and used as solid polyelectrolytes (SPEs). The thermal properties and microphase separation behavior of the tri-BCP/LiTFSI hybrids were studied. Small-angle X-ray scattering (SAXS) results revealed that all tri-BCPs formed asymmetric lamellar structures in the range of PVPS volume fractions from 12.9% to 26.1%. The microphase separation strength was enhanced with increasing the PVPS fraction (fPVPS) but was weakened as the doping ratio increased, which affected the thermal properties of the hybrids, such as melting temperature and glass transition temperature, to some extent. As compared with the PEO/LiTFSI hybrids, the PVPS-b-PEO-b-PVPS/LiTFSI hybrids could achieve both higher modulus and higher ionic conductivity, which were attributed to the physical crosslinking and the assistance in dissociation of Li+ ions by the PVPS blocks, respectively. On the basis of excellent electrical and mechanical performances, the PVPS-b-PEO-b-PVPS/LiTFSI hybrids can potentially be used as solid electrolytes in lithium-ion batteries.

7.
Molecules ; 29(9)2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38731558

ABSTRACT

Given the widespread prevalence of viruses, there is an escalating demand for antimicrobial composites. Although the composite of dialdehyde cellulose and silver nanoparticles (DAC@Ag1) exhibits excellent antibacterial properties, its weak mechanical characteristics hinder its practical applicability. To address this limitation, cellulose nanofibers (CNFs) were initially ammoniated to yield N-CNF, which was subsequently incorporated into DAC@Ag1 as an enhancer, forming DAC@Ag1/N-CNF. We systematically investigated the optimal amount of N-CNF and characterized the DAC@Ag1/N-CNF using FT-IR, XPS, and XRD analyses to evaluate its additional properties. Notably, the optimal mass ratio of N-CNF to DAC@Ag1 was found to be 5:5, resulting in a substantial enhancement in mechanical properties, with a 139.8% increase in tensile elongation and a 33.1% increase in strength, reaching 10% and 125.24 MPa, respectively, compared to DAC@Ag1 alone. Furthermore, the inhibition zones against Escherichia coli and Staphylococcus aureus were significantly expanded to 7.9 mm and 15.9 mm, respectively, surpassing those of DAC@Ag1 alone by 154.8% and 467.9%, indicating remarkable improvements in antimicrobial efficacy. Mechanism analysis highlighted synergistic effects from chemical covalent bonding and hydrogen bonding in the DAC@Ag1/N-CNF, enhancing the mechanical and antimicrobial properties significantly. The addition of N-CNF markedly augmented the properties of the composite film, thereby facilitating its broader application in the antimicrobial field.


Subject(s)
Cellulose , Escherichia coli , Metal Nanoparticles , Silver , Staphylococcus aureus , Silver/chemistry , Metal Nanoparticles/chemistry , Escherichia coli/drug effects , Staphylococcus aureus/drug effects , Cellulose/chemistry , Cellulose/analogs & derivatives , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Nanofibers/chemistry , Nanocomposites/chemistry , Microbial Sensitivity Tests , Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology , Spectroscopy, Fourier Transform Infrared
8.
Heliyon ; 10(9): e30008, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38737279

ABSTRACT

Background: Alterations in the static and dynamic characteristics of spontaneous brain activity have been extensively studied to investigate functional brain changes in migraine without aura (MwoA). However, alterations in concordance among the dynamics of spontaneous brain activity in MwoA remain largely unknown. This study aimed to determine the possibilities of diagnosis based on the concordance indices. Methods: Resting-state functional MRI scans were performed on 32 patients with MwoA and 33 matched healthy controls (HCs) in the first cohort, as well as 36 patients with MwoA and 32 HCs in the validation cohort. The dynamic indices including fractional amplitude of low-frequency fluctuation, regional homogeneity, voxel-mirrored homotopic connectivity, degree centrality and global signal connectivity were analyzed. We calculated the concordance of grey matter volume-wise (across voxels) and voxel-wise (across time windows) to quantify the degree of integration among different functional levels represented by these dynamic indices. Subsequently, the voxel-wise concordance alterations were analyzed as features for multi-voxel pattern analysis (MVPA) utilizing the support vector machine. Results: Compared with that of HCs, patients with MwoA had lower whole-grey matter volume-wise concordance, and the mean value of volume-wise concordance was negatively correlated with the frequency of migraine attacks. The MVPA results revealed that the most discriminative brain regions were the right thalamus, right cerebellar Crus II, left insula, left precentral gyrus, right cuneus, and left inferior occipital gyrus. Conclusions: Concordance alterations in the dynamics of spontaneous brain activity in brain regions could be an important feature in the identification of patients with MwoA.

9.
Bioconjug Chem ; 35(5): 693-702, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38700695

ABSTRACT

The development of oligomeric glucagon-like peptide-1 (GLP-1) and GLP-1-containing coagonists holds promise for enhancing the therapeutic potential of the GLP-1-based drugs for treating type 2 diabetes mellitus (T2DM). Here, we report a facile, efficient, and customizable strategy based on genetically encoded SpyCatcher-SpyTag chemistry and an inducible, cleavable self-aggregating tag (icSAT) scheme. icSAT-tagged SpyTag-fused GLP-1 and the dimeric or trimeric SpyCatcher scaffold were designed for dimeric or trimeric GLP-1, while icSAT-tagged SpyCatcher-fused GLP-1 and the icSAT-tagged SpyTag-fused GIP were designed for dual GLP-1/GIP (glucose-dependent insulinotropic polypeptide) receptor agonist. These SpyCatcher- and SpyTag-fused protein pairs were spontaneously ligated directly from the cell lysates. The subsequent icSAT scheme, coupled with a two-step standard column purification, resulted in target proteins with authentic N-termini, with yields ranging from 35 to 65 mg/L and purities exceeding 99%. In vitro assays revealed 3.0- to 4.1-fold increased activities for dimeric and trimeric GLP-1 compared to mono-GLP-1. The dual GLP-1/GIP receptor agonist exhibited balanced activity toward the GLP-1 receptor or the GIP receptor. All the proteins exhibited 1.8- to 3.0-fold prolonged half-lives in human serum compared to mono-GLP-1 or GIP. This study provides a generally applicable click biochemistry strategy for developing oligomeric or dual peptide/protein-based drug candidates.


Subject(s)
Click Chemistry , Glucagon-Like Peptide 1 , Glucagon-Like Peptide 1/chemistry , Humans , Receptors, Gastrointestinal Hormone/agonists , Receptors, Gastrointestinal Hormone/chemistry , Receptors, Gastrointestinal Hormone/metabolism , Drug Design , Diabetes Mellitus, Type 2/drug therapy , Gastric Inhibitory Polypeptide/chemistry , Gastric Inhibitory Polypeptide/pharmacology , Glucagon-Like Peptide-1 Receptor/agonists
10.
J Agric Food Chem ; 72(19): 10842-10852, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38708761

ABSTRACT

Guvermectin, as a novel nucleoside-like biopesticide, could increase the rice yield excellently, but the potential environmental behaviors remain unclear, which pose potential health risks. Therefore, the uptake and biotransformation of guvermectin in three types of crops (rice, lettuce, and carrot) were first evaluated with a hydroponic system. Guvermectin could be rapidly absorbed and reached equilibrium in roots (12-36 h) and shoots (24-60 h) in three plants, and guvermectin was also vulnerable to dissipation in roots (t1/2 1.02-3.65 h) and shoots (t1/2 9.30-17.91 h). In addition, 8 phase I and 2 phase II metabolites, transformed from guvermectin degradation in vivo and in vitro exposure, were identified, and one was confirmed as psicofuranine, which had antibacterial and antitumor properties; other metabolites were nucleoside-like chemicals. Molecular simulation and quantitative polymerase chain reaction further demonstrated that guvermectin was metabolized by the catabolism pathway of an endogenous nucleotide. Guvermectin had similar metabolites in three plants, but the biotransformation ability had a strong species dependence. In addition, all the metabolites exhibit neglectable toxicities (bioconcentration factor <2000 L/kg b.w., LC50,rat > 5000 mg/kg b.w.) by prediction. The study provided valuable evidence for the application of guvermectin and a better understanding of the biological behavior of nucleoside-like pesticides.


Subject(s)
Biotransformation , Daucus carota , Ivermectin , Lactuca , Oryza , Plant Roots , Ivermectin/metabolism , Ivermectin/analogs & derivatives , Plant Roots/metabolism , Plant Roots/chemistry , Plant Roots/growth & development , Lactuca/metabolism , Lactuca/chemistry , Lactuca/growth & development , Oryza/metabolism , Oryza/growth & development , Oryza/chemistry , Daucus carota/metabolism , Daucus carota/chemistry , Crops, Agricultural/metabolism , Crops, Agricultural/chemistry , Crops, Agricultural/growth & development
11.
Commun Med (Lond) ; 4(1): 84, 2024 May 09.
Article in English | MEDLINE | ID: mdl-38724730

ABSTRACT

BACKGROUND: Artificial Intelligence(AI)-based solutions for Gleason grading hold promise for pathologists, while image quality inconsistency, continuous data integration needs, and limited generalizability hinder their adoption and scalability. METHODS: We present a comprehensive digital pathology workflow for AI-assisted Gleason grading. It incorporates A!MagQC (image quality control), A!HistoClouds (cloud-based annotation), Pathologist-AI Interaction (PAI) for continuous model improvement, Trained on Akoya-scanned images only, the model utilizes color augmentation and image appearance migration to address scanner variations. We evaluate it on Whole Slide Images (WSI) from another five scanners and conduct validations with pathologists to assess AI efficacy and PAI. RESULTS: Our model achieves an average F1 score of 0.80 on annotations and 0.71 Quadratic Weighted Kappa on WSIs for Akoya-scanned images. Applying our generalization solution increases the average F1 score for Gleason pattern detection from 0.73 to 0.88 on images from other scanners. The model accelerates Gleason scoring time by 43% while maintaining accuracy. Additionally, PAI improve annotation efficiency by 2.5 times and led to further improvements in model performance. CONCLUSIONS: This pipeline represents a notable advancement in AI-assisted Gleason grading for improved consistency, accuracy, and efficiency. Unlike previous methods limited by scanner specificity, our model achieves outstanding performance across diverse scanners. This improvement paves the way for its seamless integration into clinical workflows.


Gleason grading is a well-accepted diagnostic standard to assess the severity of prostate cancer in patients' tissue samples, based on how abnormal the cells in their prostate tumor look under a microscope. This process can be complex and time-consuming. We explore how artificial intelligence (AI) can help pathologists perform Gleason grading more efficiently and consistently. We build an AI-based system which automatically checks image quality, standardizes the appearance of images from different equipment, learns from pathologists' feedback, and constantly improves model performance. Testing shows that our approach achieves consistent results across different equipment and improves efficiency of the grading process. With further testing and implementation in the clinic, our approach could potentially improve prostate cancer diagnosis and management.

12.
Angew Chem Int Ed Engl ; : e202407277, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38780892

ABSTRACT

Chiral multi-resonance thermally activated delayed fluorescence (CP-MR-TADF) materials hold promise for circularly polarized organic light-emitting diode (CP-OLED) and 3D display. Herein, we present two pairs of tetraborated intrinsically axial CP-MR-TADF materials, R/S-BDBF-BOH and R/S-BDBT-BOH, with conjugation-extended bidibenzo[b,d]furan and bidibenzo[b,d]thiophene as chiral sources, which effectively participate in the distribution of frontier molecular orbitals. Due to the heavy-atom effect, sulfur atoms are introduced to accelerate the reverse intersystem crossing process and increase efficiency of molecules. R/S-BDBF-BOH and R/S-BDBT-BOH manifest ultra-pure blue emission peaking at 458/459 nm with full width at half maximum of 27 nm (0.16 eV), photoluminescence quantum yields of 90%/91% and dissymmetry factors (|gPL|) of 6.8 × 10-4/8.5 × 10-4, respectively. Correspondingly, the CP-OLEDs exhibit good performances with external quantum efficiency of 30.1% and |gEL| factors of 1.2 × 10-3.

13.
Adv Sci (Weinh) ; : e2400729, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38774942

ABSTRACT

The Carbon-binder domain (CBD) plays a pivotal role in the performance of lithium-ion battery electrodes. The heterogeneous distribution of CBD across the electrode has garnered significant attention. However, a thorough understanding of how this CBD inhomogeneity affects anode performance remains a crucial pursuit, especially when considering the inherent material variations present in the SiO/Graphite (SiO/Gr) composite anode. In this study, an electro-chemo-mechanical model is established that provides a detailed geometric description of the particles. This model allows to quantitatively uncover the effects of CBD inhomogeneity on the fundamental behaviors of the SiO/Gr composite anode. The findings indicate that reducing the proportion of CBD in the upper domain (near the anode surface) compared to the lower domain (near the current collector) positively influences electrochemical performance, particularly in terms of capacity and Li plating. However, such an arrangement introduces potential risks of mechanical failures, and it is recommended to incorporate a higher proportion of CBD alongside the SiO particles. Finally, an anode design with a lower CBD proportion in the upper domain exhibits superior rate performance. This study represents a pioneering modeling exploration of CBD inhomogeneity, offering a promising multiphysics model with significant potential for informing advanced battery design considerations.

14.
Transfus Apher Sci ; 63(4): 103940, 2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38781881

ABSTRACT

Abnormal plasma uric acid (UA) levels, the lipid profile, and plasma proteins in blood are associated with a range of adverse health outcomes. This multicenter, prospective cohort study aimed to determine the possible effects of multiple apheresis plasma donations on plasma UA levels, the lipid profile, and major proteins in plasma donors. Participants were enrolled from 1 April 2021 to 31 August 2022. When their plasma UA (men: >420 µmol/L, women: >360 µmol/L) and/or lipid levels (total cholesterol [TC]: ≥6.2 mmol/L, triglycerides [TGs]: ≥2.3 mmol/L, low-density lipoprotein cholesterol: ≥4.1 mmol/L, or high-density lipoprotein cholesterol [HDL-C]: <1.0 mmol/L) were abnormal at their first plasma donation, the enrolled participants were followed up until they had completed 10 plasma donations. A total of 11485 participants were enrolled, of whom 1861 met the inclusion criteria. During the study period, 320 donors completed 10 plasma donations. None of the participants took any corrective medicine for their abnormal index. The measured parameters were significantly different from the first to the tenth plasma donations (donors with asymptomatic hyperuricemia: UA, P < 0.001; donors with asymptomatic hyperlipidemia: HDL-C, P < 0.001; TC, P = 0.025; TGs, P < 0.001; apolipoprotein B, P = 0.025; all of the plasma donors, immunoglobulin G, P < 0.001). The levels of HDL-C, TC, and apolipoprotein B were increased, and the levels of UA, TGs, and immunoglobulin G were decreased over this time. However, immunoglobulin G levels were still in the normal range. Moreover, the changes in these parameters were closely associated with the frequency of plasma donation during the study period. Repeated apheresis plasma donations can reduce plasma UA and TG levels and increase HDL-C levels; and further evaluation of the clinical significance with a larger sample size is required.

15.
Article in English | MEDLINE | ID: mdl-38769349

ABSTRACT

This study delves into the clinical implications of cyclin-dependent kinase inhibitor 2 (CDKN2) deletion in adult T-lineage acute lymphoblastic leukemia (T-ALL). Among 241 patients included in this study, 57 had CDKN2 deletion and 184 had CDKN2 wild-type (WT), and 165 underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) and 76 did not undergo allo-HSCT. CDKN2 deletion correlated with higher white blood cell count, more high-risk diseases, and complex karyotype. The 5-year overall survival (OS) was 36.8% and 58.2% (P < 0.001), 5-year disease-free survival (DFS) was 47.1% and 59.3% (P = 0.018), and 5-year cumulative incidence of relapse (CIR) was 33.7% and 22.3% (P = 0.019) in patients with CDKN2 deletion and WT, respectively. Multivariate analysis identified CDKN2 deletion as an independent adverse prognostic factor for OS (HR 2.11, P = 0.003). In the CDKN2 deletion subgroup, landmark analysis showed that the 5-year OS was 56.7% and 19% (P = 0.002) for patients who underwent allo-HSCT and those who did not, respectively. And multivariate analysis confirmed the beneficial role of allo-HSCT in OS (HR 0.23, P < 0.001). In conclusion, CDKN2 deletion was associated with a poor prognosis in adult T-ALL, and allo-HSCT might be beneficial for this population.

16.
Biochim Biophys Acta Mol Basis Dis ; 1870(6): 167210, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38704001

ABSTRACT

Oxaliplatin has been included as a basal drug in various chemotherapy regimens for colorectal cancer (CRC), a global health concern. However, acquired resistance to oxaliplatin affects the prognosis. This study aimed to determine whether the consumption of a KD increases the sensitivity of CRC cells to oxaliplatin via the inhibition of a classical stem cell marker, Krupple-like factor 5 (KLF5). KLF5 functions as a transcription factor for the leukemia inhibitory factor (LIF) and directly binds to its promoter region. LIF upregulation induces dephosphorylation of metal regulatory transcription factor 1 (MTF1), which is recruited to the promoter area of Ferroportin (FPN1), the only cellular iron exporter. FPN1 upregulation reduces the labile iron pool (LIP) and ferroptosis in CRC cells. KLF5 knockdown inhibits the LIF/MTF1/FPN1 axis and induces iron overload, thereby conferring sensitivity to oxaliplatin to CRC cells. KD mimicked KLF5 silencing and sensitized CRC cells to oxaliplatin via a similar mechanism. Thus, potential correlations were observed among ketogenesis, stemness, and iron homeostasis. This finding can be used to formulate a new strategy for overcoming oxaliplatin resistance in patients with CRC.

17.
Toxicol Appl Pharmacol ; 487: 116969, 2024 May 12.
Article in English | MEDLINE | ID: mdl-38744347

ABSTRACT

Cysteine and glycine-rich protein 2 (CSRP2) is expressed differently in numerous cancers and plays a key role in carcinogenesis. However, the role of CSRP2 in glioma is unknown. This study sought to determine the expression profile and clinical significance of CSRP2 in glioma and explore its biological functions and mechanisms via lentivirus-mediated CSRP2 silencing experiments. Increased CSRP2 was frequently observed in gliomas, which was associated with clinicopathological characteristics and an unfavourable prognosis. Decreasing CSRP2 led to the suppression of malignant proliferation, metastasis and stemness in glioma cells while causing hypersensitivity to chemotherapeutic drugs. Mechanistic investigations revealed that CSRP2 plays a role in mediating the Notch signalling cascade. Silencing CSRP2 decreased the levels of Notch1, cleaved Notch1, HES1 and HEY1, suppressing the Notch signalling cascade. Reactivation of Notch markedly diminished the tumour-inhibiting effects of CSRP2 silencing on the malignant phenotypes of glioma cells. Notably, CSRP2-silencing glioma cells exhibited reduced potential in the formation of xenografts in nude mice in vivo, which was associated with an impaired Notch signalling cascade. These results showed that CSRP2 is overexpressed in glioma and has a crucial role in sustaining the malignant phenotypes of glioma, suggesting that targeting CSRP2 could be a promising strategy for glioma treatment.

18.
Mil Med Res ; 11(1): 31, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38797843

ABSTRACT

Aging and regeneration represent complex biological phenomena that have long captivated the scientific community. To fully comprehend these processes, it is essential to investigate molecular dynamics through a lens that encompasses both spatial and temporal dimensions. Conventional omics methodologies, such as genomics and transcriptomics, have been instrumental in identifying critical molecular facets of aging and regeneration. However, these methods are somewhat limited, constrained by their spatial resolution and their lack of capacity to dynamically represent tissue alterations. The advent of emerging spatiotemporal multi-omics approaches, encompassing transcriptomics, proteomics, metabolomics, and epigenomics, furnishes comprehensive insights into these intricate molecular dynamics. These sophisticated techniques facilitate accurate delineation of molecular patterns across an array of cells, tissues, and organs, thereby offering an in-depth understanding of the fundamental mechanisms at play. This review meticulously examines the significance of spatiotemporal multi-omics in the realms of aging and regeneration research. It underscores how these methodologies augment our comprehension of molecular dynamics, cellular interactions, and signaling pathways. Initially, the review delineates the foundational principles underpinning these methods, followed by an evaluation of their recent applications within the field. The review ultimately concludes by addressing the prevailing challenges and projecting future advancements in the field. Indubitably, spatiotemporal multi-omics are instrumental in deciphering the complexities inherent in aging and regeneration, thus charting a course toward potential therapeutic innovations.


Subject(s)
Aging , Genomics , Proteomics , Regenerative Medicine , Aging/physiology , Humans , Regenerative Medicine/methods , Regenerative Medicine/trends , Genomics/methods , Proteomics/methods , Metabolomics/methods , Epigenomics/methods , Multiomics
19.
World J Stem Cells ; 16(5): 560-574, 2024 May 26.
Article in English | MEDLINE | ID: mdl-38817327

ABSTRACT

BACKGROUND: Alveolar bone defects caused by inflammation are an urgent issue in oral implant surgery that must be solved. Regulating the various phenotypes of macrophages to enhance the inflammatory environment can significantly affect the progression of diseases and tissue engineering repair process. AIM: To assess the influence of interleukin-10 (IL-10) on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) following their interaction with macrophages in an inflammatory environment. METHODS: IL-10 modulates the differentiation of peritoneal macrophages in Wistar rats in an inflammatory environment. In this study, we investigated its impact on the proliferation, migration, and osteogenesis of BMSCs. The expression levels of signal transducer and activator of transcription 3 (STAT3) and its activated form, phosphorylated-STAT3, were examined in IL-10-stimulated macrophages. Subsequently, a specific STAT3 signaling inhibitor was used to impede STAT3 signal activation to further investigate the role of STAT3 signaling. RESULTS: IL-10-stimulated macrophages underwent polarization to the M2 type through substitution, and these M2 macrophages actively facilitated the osteogenic differentiation of BMSCs. Mechanistically, STAT3 signaling plays a crucial role in the process by which IL-10 influences macrophages. Specifically, IL-10 stimulated the activation of the STAT3 signaling pathway and reduced the macrophage inflammatory response, as evidenced by its diminished impact on the osteogenic differentiation of BMSCs. CONCLUSION: Stimulating macrophages with IL-10 proved effective in improving the inflammatory environment and promoting the osteogenic differentiation of BMSCs. The IL-10/STAT3 signaling pathway has emerged as a key regulator in the macrophage-mediated control of BMSCs' osteogenic differentiation.

20.
Front Psychol ; 15: 1354810, 2024.
Article in English | MEDLINE | ID: mdl-38817836

ABSTRACT

Objective: This study endeavors to translate and psycho-metrically validate the metacognitive awareness inventory scale (MAS) for nursing students in China. Method: A total of 592 nursing students were enlisted from four universities situated in the eastern, southern, western, and northern regions of China. Content validity and reliability were evaluated using the content validity index and item-total correlation coefficient, and Cronbach's alpha coefficients, respectively. Convergent validity examined the goodness of fit among sub-scales through the average extracted variance and composite reliability. Results: Exploratory factor analysis confirmed the first-order and second-order factor models, contributing to a cumulative variance of 89.4 and 59.5%, respectively. The Cronbach's alpha values were 0.963 and 0.801, respectively. Confirmatory factor analysis outcomes indicated an excellent overall fit index for the model, satisfying the convergent validity criteria and achieving a target coefficient of 96.0%, which is consistent with the original scale structure. Conclusion: The Chinese version of the MAS (C-MAS) is a reliable and valid instrument for assessing metacognitive awareness among Chinese nursing students. Further research should consider a broader sample of nursing students across China to reinforce the scale's applicability.

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