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1.
J Behav Addict ; 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38829707

ABSTRACT

Objective: To investigate the rates of problematic mobile phone use (PMPU) and chronotypes in young adults, and examine the associations of PMPU with chronotypes, as well as its gender differences. Furthermore, we explored the moderating role of PER3 gene DNA methylation on the associations. Methods: From April to May 2019, a total of 1,179 young adults were selected from 2 universities in Anhui and Jiangxi provinces. The Self-rating Questionnaire for Adolescent Problematic Mobile Phone Use (SQAPMPU) and reduced Morningness-Eveningness Questionnaire (rMEQ) were adopted to investigate PMPU and chronotypes in young adults, respectively. Moreover, 744 blood samples were collected to measure PER3 gene DNA methylation. Multivariate logistic regression models were established to analyze the associations between PMPU and chronotypes. Moderating analysis was used to determine whether PER3 gene DNA methylation moderated the relationships between PMPU and chronotypes. Results: The prevalence of PMPU, morning chronotypes (M-types), neutral chronotypes (N-types), and evening chronotypes (E-types) of young adults were 24.6%, 18.4%, 71.1%, and 10.5%, respectively. Multivariate logistic regression results indicated that PMPU was positively correlated with E-types (OR = 3.53, 95%CI: 2.08-6.00), and the association was observed only in females after stratified by gender (OR = 5.36, 95%CI: 2.70-10.67). Furthermore, PER3 gene DNA methylation has a negative moderating role between PMPU and chronotypes and has a sex-based difference. Conclusions: This study can provide valuable information for the prevention and control of circadian rhythm disturbance among young adults from the perspective of epidemiology and biological etiology.

2.
Clin Cosmet Investig Dermatol ; 17: 1281-1295, 2024.
Article in English | MEDLINE | ID: mdl-38835517

ABSTRACT

Background: Ferroptosis is a type of cell death characterized by the accumulation of iron-dependent lethal lipid peroxides, which is associated with various pathophysiological processes. Psoriasis is a chronic autoimmune skin disease accompanied by abnormal immune cell infiltration and excessive production of lipid reactive oxygen species (ROS). Currently, its pathogenesis remains elusive, especially the potential role of ferroptosis in its pathophysiological process. Methods: The microarrays GSE13355 (58 psoriatic skin specimens versus 122 healthy skin specimens) and the ferroptosis database were employed to identify the common differentially expressed genes (DEGs) associated with psoriasis and ferroptosis. The functions of common DEGs were investigated through functional enrichment analysis and protein-protein interaction analysis. The potential diagnostic markers for psoriasis among the common DEGs were identified using four machine-learning algorithms. DGIdb was utilized to explore potential therapeutic agents for psoriasis. Additionally, CIBERSORT was employed to investigate immune infiltration in psoriasis. Results: A total of 8 common DEGs associated with psoriasis and ferroptosis were identified, which are involved in intercellular signaling and affect pathways of cell response to stress and stimulation. Four machine-learning algorithms were employed to identify poly (ADP-ribose) polymerase 12 (PARP12), frizzled homolog 7 (FZD7), and arachidonate 15-lipoxygenase (ALOX15B) among the eight common DEGs as potential diagnostic markers for psoriasis. A total of 18 drugs targeting the five common DEGs were identified as potential candidates for treating psoriasis. Additionally, significant changes were observed in the immune microenvironment of patients with psoriasis. Conclusion: This study has contributed to our enhanced comprehension of ferroptosis-related genes as potential biomarkers for psoriasis diagnosis, as well as the alterations in the immune microenvironment associated with psoriasis. Our findings offer valuable insights into the diagnosis and treatment of psoriasis.

3.
Eur J Med Chem ; 271: 116451, 2024 May 05.
Article in English | MEDLINE | ID: mdl-38691892

ABSTRACT

The potent antibacterial activity and low resistance of antimicrobial peptides (AMPs) render them potential candidates for treating multidrug-resistant bacterial infections. Herein, a minimalist design strategy was proposed employing the "golden partner" combination of arginine (R) and tryptophan (W), along with a dendritic structure to design AMPs. By extension, the α/ε-amino group and the carboxyl group of lysine (K) were utilized to link R and W, forming dendritic peptide templates αRn(εRn)KWm-NH2 and αWn(εWn)KRm-NH2, respectively. The corresponding linear peptide templates R2nKWm-NH2 and W2nKRm-NH2 were used as controls. Their physicochemical properties, activity, toxicity, and stability were compared. Among these new peptides, the dendritic peptide R2(R2)KW4 was screened as a prospective candidate owing to its preferable antibacterial properties, biocompatibility, and stability. Additionally, R2(R2)KW4 not only effectively restrained the progression of antibiotic resistance, but also demonstrated synergistic utility when combined with conventional antibiotics due to its unique membrane-disruptive mechanism. Furthermore, R2(R2)KW4 possessed low toxicity (LD50 = 109.31 mg/kg) in vivo, while efficiently clearing E. coli in pulmonary-infected mice. In conclusion, R2(R2)KW4 has the potential to become an antimicrobial regent or adjuvant, and the minimalist design strategy of dendritic peptides provides innovative and encouraging thoughts in designing AMPs.


Subject(s)
Anti-Bacterial Agents , Arginine , Microbial Sensitivity Tests , Tryptophan , Tryptophan/chemistry , Tryptophan/pharmacology , Animals , Arginine/chemistry , Arginine/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/chemical synthesis , Mice , Antimicrobial Peptides/chemistry , Antimicrobial Peptides/pharmacology , Antimicrobial Peptides/chemical synthesis , Structure-Activity Relationship , Molecular Structure , Cell Membrane/drug effects , Dose-Response Relationship, Drug , Bacterial Infections/drug therapy , Humans , Escherichia coli/drug effects
4.
Angew Chem Int Ed Engl ; : e202404816, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38788189

ABSTRACT

Room-temperature sodium-sulfur (RT Na-S) batteries, noted for their low material costs and high energy density, are emerging as a promising alternative to LIBs in various applications including power grids and standalone renewable energy systems. These batteries are commonly assembled with glass fiber membranes, which face significant challenges like the dissolution of polysulfides, sluggish sulfur conversion kinetics, and the dendrites growth. Here, we develop an amorphous FeSnOx nanosheet with hierarchical vacancies, including abundant oxygen vacancies (Ovs) and nano-sized perforations, that can be assembled into a multifunctional layer overlaying commercial separators for RT Na-S batteries. The Ovs offer strong adsorption and abundant catalytic sites for polysulfides, while the defect concentration is finely tuned to elucidate the polysulfides conversion mechanisms. The nano-sized perforations aid in regulating Na ions transport, resulting in uniform Na deposition. Moreover, the strategic addition of trace amounts of Ti3C2 forms an amorphous/crystalline interface that significantly improves the mechanical properties of the separator and suppresses dendrite growth. As a result, the task-specific layer achieves ultra-light (~0.1mg cm-2), ultra-thin (~200nm), and ultra-robust (modulus = 4.9GPa) characteristics. Consequently, the RT Na-S battery maintained a high capacity of 610.3mAh g-1 and an average Coulombic efficiency of 99.9% after 400 cycles at 0.5C.

5.
J Transl Int Med ; 12(2): 197-208, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38779116

ABSTRACT

Background and Objectives: The Alberta Stroke Program CT Score (ASPECTS) is a widely used rating system for assessing infarct extent and location. We aimed to investigate the prognostic value of ASPECTS subregions' involvement in the long-term functional outcomes of acute ischemic stroke (AIS). Materials and Methods: Consecutive patients with AIS and anterior circulation large-vessel stenosis and occlusion between January 2019 and December 2020 were included. The ASPECTS score and subregion involvement for each patient was assessed using posttreatment magnetic resonance diffusion-weighted imaging. Univariate and multivariable regression analyses were conducted to identify subregions related to 3-month poor functional outcome (modified Rankin Scale scores, 3-6) in the reperfusion and medical therapy cohorts, respectively. In addition, prognostic efficiency between the region-based ASPECTS and ASPECTS score methods were compared using receiver operating characteristic curves and DeLong's test. Results: A total of 365 patients (median age, 64 years; 70% men) were included, of whom 169 had poor outcomes. In the reperfusion therapy cohort, multivariable regression analyses revealed that the involvement of the left M4 cortical region in left-hemisphere stroke (adjusted odds ratio [aOR] 5.39, 95% confidence interval [CI] 1.53-19.02) and the involvement of the right M3 cortical region in right-hemisphere stroke (aOR 4.21, 95% CI 1.05-16.78) were independently associated with poor functional outcomes. In the medical therapy cohort, left-hemisphere stroke with left M5 cortical region (aOR 2.87, 95% CI 1.08-7.59) and caudate nucleus (aOR 3.14, 95% CI 1.00-9.85) involved and right-hemisphere stroke with right M3 cortical region (aOR 4.15, 95% CI 1.29-8.18) and internal capsule (aOR 3.94, 95% CI 1.22-12.78) affected were related to the increased risks of poststroke disability. In addition, region-based ASPECTS significantly improved the prognostic efficiency compared with the conventional ASPECTS score method. Conclusion: The involvement of specific ASPECTS subregions depending on the affected hemisphere was associated with worse functional outcomes 3 months after stroke, and the critical subregion distribution varied by clinical management. Therefore, region-based ASPECTS could provide additional value in guiding individual decision making and neurological recovery in patients with AIS.

6.
Front Immunol ; 15: 1397005, 2024.
Article in English | MEDLINE | ID: mdl-38779660

ABSTRACT

As major components of the tumor microenvironment, both mesenchymal stem cells (MSCs) and macrophages can be remodelled and exhibit different phenotypes and functions during tumor initiation and progression. In recent years, increasing evidence has shown that tumor-associated macrophages (TAMs) play a crucial role in the growth, metastasis, and chemotherapy resistance of hematological malignancies, and are associated with poor prognosis. Consequently, TAMs have emerged as promising therapeutic targets. Notably, MSCs exert a profound influence on modulating immune cell functions such as macrophages and granulocytes, thereby playing a crucial role in shaping the immunosuppressive microenvironment surrounding tumors. However, in hematological malignancies, the cellular and molecular mechanisms underlying the interaction between MSCs and macrophages have not been clearly elucidated. In this review, we provide an overview of the role of TAMs in various common hematological malignancies, and discuss the latest advances in understanding the interaction between MSCs and macrophages in disease progression. Additionally, potential therapeutic approaches targeting this relationship are outlined.


Subject(s)
Mesenchymal Stem Cells , Tumor Microenvironment , Humans , Mesenchymal Stem Cells/immunology , Mesenchymal Stem Cells/metabolism , Tumor Microenvironment/immunology , Animals , Hematologic Neoplasms/immunology , Hematologic Neoplasms/therapy , Hematologic Neoplasms/pathology , Tumor-Associated Macrophages/immunology , Tumor-Associated Macrophages/metabolism , Macrophages/immunology , Macrophages/metabolism , Cell Communication/immunology
7.
Article in English | MEDLINE | ID: mdl-38775214

ABSTRACT

OBJECTIVE: The present study aimed to investigate the specific alterations of brain networks in patients with post-stroke depression (PSD), and further assist in elucidating the brain mechanisms underlying the PSD which would provide supporting evidence for early diagnosis and interventions for the disease. METHODS: Resting-state functional magnetic resonace imaging data were acquired from 82 nondepressed stroke patients (Stroke), 39 PSD patients, and 74 healthy controls (HC). Voxel-wise degree centrality (DC) conjoined with seed-based functional connectivity (FC) analyses were performed to investigate the PSD-related connectivity alterations. The relationship between these alterations and depression severity was further examined in PSD patients. RESULTS: Relative to both Stroke and HC groups, (1) PSD showed increased centrality in regions within the default mode network (DMN), including contralesional angular gyrus (ANG), posterior cingulate cortex (PCC), and hippocampus (HIP). DC values in contralesional ANG positively correlated with the Patient Health Questionnaire-9 (PHQ-9) scores in PSD group. (2) PSD exhibited increased connectivity between these three seeds showing altered DC and regions within the DMN: bilateral medial prefrontal cortex and middle temporal gyrus and ipsilesional superior parietal gyrus, and regions outside the DMN: bilateral calcarine, ipsilesional inferior occipital gyrus and contralesional lingual gyrus, while decreased connectivity between contralesional ANG and contralesional supramarginal gyrus. Moreover, these FC alterations could predict PHQ-9 scores in PSD group. INTERPRETATION: These findings highlight that PSD was related with increased functional connectivity strength in some areas within the DMN, which might be attribute to the specific alterations of connectivity between within DMN and outside DMN regions in PSD.

8.
Viruses ; 16(5)2024 04 29.
Article in English | MEDLINE | ID: mdl-38793591

ABSTRACT

In recent years, pseudorabies virus (PRV) variants have resulted in an epidemic in swine herds and huge economic losses in China. Therefore, it is essential to develop an efficacious vaccine against the spread of PRV variants. Here, the triple-gene-deletion virus and the triple-gene-deletion plus gC virus were constructed by homologous recombination (HR). And then, their growth capacity, proliferation ability, and immune efficacy were evaluated. The results showed that the growth kinetics of the recombinant viruses were similar to those of the parental strain PRV-AH. Compared with the triple-gene-deletion virus group, the more dominant level of neutralizing antibody (NA) can be induced in the triple-gene-deletion plus gC virus group with the same 106.0 TCID50 dose after 4 and 6 weeks post-initial immunization (PII) (p < 0.0001). In addition, the antibody titers in mice immunized with the triple-gene-deletion plus gC virus were significantly higher than those immunized with triple-gene deletion virus with the same 105.0 TCID50 dose after 6 weeks PII (p < 0.001). More importantly, in the triple-gene-deletion plus gC virus group with 105.0 TCID50, the level of NA was close to that in the triple-gene deletion virus group with 106.0 TCID50 at 6 weeks PII. Meanwhile, the cytokines IL-4 and IFN-γ in sera were tested by enzyme-linked immunosorbent assay (ELISA) in each group. The highest level of IL-4 or IFN-γ was also elicited in the triple-gene deletion plus gC virus group at a dose of 106.0 TCID50. After challenge with PRV-AH, the survival rates of the triple-gene deletion plus gC virus immunized groups were higher than those of other groups. In immunized groups with 105.0 TCID50, the survival rate shows a significant difference between the triple-gene deletion plus gC virus group (75%, 6/8) and the triple-gene deletion virus group (12.5%, 1/8). In general, the immune efficacy of the PRV TK/gI/gE-deleted virus can be increased with additional gC insertion in mice, which has potential for developing an attenuated vaccine candidate for PRV control.


Subject(s)
Antibodies, Neutralizing , Antibodies, Viral , Gene Deletion , Herpesvirus 1, Suid , Pseudorabies Vaccines , Pseudorabies , Animals , Herpesvirus 1, Suid/genetics , Herpesvirus 1, Suid/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , Mice , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Pseudorabies/prevention & control , Pseudorabies/immunology , Pseudorabies/virology , Pseudorabies Vaccines/immunology , Pseudorabies Vaccines/genetics , Pseudorabies Vaccines/administration & dosage , Mice, Inbred BALB C , Swine , Female , Viral Envelope Proteins/genetics , Viral Envelope Proteins/immunology , Homologous Recombination , Cytokines/metabolism , China
9.
Front Cardiovasc Med ; 11: 1325947, 2024.
Article in English | MEDLINE | ID: mdl-38803665

ABSTRACT

Background and aims: This study aimed to evaluate whether there is a J-curve association between blood pressure (BP) and carotid artery intima-media thickening (CAIT) and estimate the effect of the turning point of BP on CAIT. Methods and results: Data from 111,494 regular physical examinations conducted on workers and retirees (aged 18 years or older) between January 2011 and December 2016, exported from the hospital information system, were analyzed. Restricted cubic splines (RCS) logistic regression was employed to access the association of BP with CAIT, and Bayesian benchmark dose methods were used to estimate the benchmark dose as the departure point of BP measurements. All the pnon-linear values of BP measurements were less than 0.05 in the RCS logistic regression models. Both systolic blood pressure (SBP) and diastolic blood pressure (DBP) had J-curve associations with the risk of CAIT at a turning point around 120/70 mmHg in the RCS. The benchmark dose for a 1% change in CAIT risk was estimated to be 120.64 mmHg for SBP and 72.46 mmHg for DBP. Conclusion: The J-curve associations between SBP and DBP and the risk of CAIT were observed in the general population in southern China, and the turning point of blood pressure for significantly reducing the risk of CAIT was estimated to be 120.64/72.46 mmHg for SBP/DBP.

10.
Front Med (Lausanne) ; 11: 1371183, 2024.
Article in English | MEDLINE | ID: mdl-38765258

ABSTRACT

Interstitial pneumonia is the most common and serious secondary lesion of dermatomyositis. In some cases, patients may develop severe acute pneumonia that can quickly progress to respiratory failure, resulting in high mortality rates. A 57-year-old woman with dermatomyositis and interstitial pulmonary fibrosis experienced severe hypoxemia due to pulmonary infection. Despite receiving various treatments after entering the intensive care unit (ICU), such as anti-infection therapy, lung recruitment, prone position ventilation, sedative and muscle relaxation, the patient's oxygen saturation continued to decline. Electrical impedance tomography (EIT) monitoring revealed that prone position could not improve ventilation homogeneity. However, the patient's ventilation/perfusion (V/Q) matching significantly improved 10 min after initiation of supine position ventilation combined with inhalation of nitric oxide (iNO). The patient's PaO2/FiO2 (P/F) ratio increased from 86 mmHg to 150 mmHg at 30 min post-treatment. iNO treatment continued for 2 days. Then the patient's condition improved and she was successfully weaned off the ventilator with rigorous monitoring and symptomatic care. The implementation of mechanical ventilation combined with iNO therapy rapidly improved V/Q matching and oxygenation in a patient with hypoxemia caused by dermatomyositis complicated with interstitial pneumonia. This approach successfully avoided the need for invasive extracorporeal membrane oxygenation (ECMO) support.

11.
Psychol Sport Exerc ; 74: 102678, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38821251

ABSTRACT

INTRODUCTION: Long-term motor skill training has been shown to induce anatomical and functional neuroplasticity. World class gymnasts (WCGs) provide a unique opportunity to investigate the effect of long-term intensive training on neuroplasticity. Previous resting-state fMRI studies have demonstrated a high efficient information processing related to motor and cognitive functions in gymnasts compared with healthy controls (HCs). However, most research treated brain signals as static, overlooking the fact that the brain is a complex and dynamic system. In this study, we employed functional stability, a new metric based on dynamic functional connectivity (FC), to examine the impact of long-term intensive training on the functional architecture in the WCGs. METHODS: We first conducted a voxel-wise analysis of functional stability between the WCGs and HCs. Then, we applied FC density (FCD) to explore whether regions with modified functional stability were also accompanied by changes in connection patterns in the WCGs. We identified overlapping regions showing significant differences in both functional stability and FCD. Finally, we applied seed-based correlation analysis (SCA) to determine the detailed changes in connection patterns between the WCGs and HCs within these overlapping regions. RESULTS: Compared with the HCs, the WCGs exhibited higher functional stability in the bilateral angular gyrus (AG), bilateral inferior temporal gyrus (ITG), bilateral precentral gyrus, and right superior frontal gyrus and lower functional stability in the bilateral hippocampus, bilateral caudate, right rolandic operculum, left superior temporal gyrus, right middle frontal gyrus, right middle cingular cortex, and right precuneus than the HCs. We found that the bilateral AG and ITG not only showed higher functional stability but also increased global and long-range FCD in the WCGs relative to the HCs. The right precuneus displayed lower functional stability as well as decreased local, long-range, and global FCD in the WCGs. Both AG and ITG showed higher FC with regions in the default mode network (DMN) in the WCGs than in the HCs. CONCLUSIONS: The increased functional stability in the AG and ITG might be associated with enhanced functional integration within the DMN in the WCGs. These findings may offer new spatiotemporal evidence for the impact of long-term intensive training on neuroplasticity.

12.
Toxicol Appl Pharmacol ; 487: 116954, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38705402

ABSTRACT

Dual-specificity phosphatase 26 (DUSP26) acts as a pivotal player in the transduction of signalling cascades with its dephosphorylating activity. Currently, DUSP26 attracts extensive attention due to its particular function in several pathological conditions. However, whether DUSP26 plays a role in kidney ischaemia-reperfusion (IR) injury is unknown. Aims of the current work were to explore the relevance of DUSP26 in kidney IR damage. DUSP26 levels were found to be decreased in renal tubular epithelial cells following hypoxia-reoxygenation (HR) and kidney samples subjected to IR treatments. DUSP26-overexpressed renal tubular epithelial cells exhibited protection against HR-caused apoptosis and inflammation, while DUSP26-depleted renal tubular epithelial cells were more sensitive to HR damage. Upregulation of DUSP26 in rat kidneys by infecting adenovirus expressing DUSP26 markedly ameliorated kidney injury caused by IR, while also effectively reducing apoptosis and inflammation. The mechanistic studies showed that the activation of transforming growth factor-ß-activated kinase 1 (TAK1)-JNK/p38 MAPK, contributing to kidney injury under HR or IR conditions, was restrained by increasing DUSP26 expression. Pharmacological restraint of TAK1 markedly diminished DUSP26-depletion-exacebated effects on JNK/p38 activation and HR injury of renal tubular cells. The work reported a renal-protective function of DUSP26, which protects against IR-related kidney damage via the intervention effects on the TAK1-JNK/p38 axis. The findings laid a foundation for understanding the molecular pathogenesis of kidney IR injury and provide a prospective target for treating this condition.


Subject(s)
Apoptosis , Epithelial Cells , Kidney Tubules , MAP Kinase Kinase Kinases , Rats, Sprague-Dawley , Reperfusion Injury , p38 Mitogen-Activated Protein Kinases , Animals , Reperfusion Injury/pathology , MAP Kinase Kinase Kinases/metabolism , MAP Kinase Kinase Kinases/genetics , Epithelial Cells/metabolism , Epithelial Cells/pathology , Male , Kidney Tubules/pathology , Kidney Tubules/metabolism , Rats , p38 Mitogen-Activated Protein Kinases/metabolism , Dual-Specificity Phosphatases/metabolism , Dual-Specificity Phosphatases/genetics , Cell Line , Acute Kidney Injury/pathology , Acute Kidney Injury/metabolism , Inflammation/pathology , Inflammation/metabolism , MAP Kinase Signaling System/physiology , Mitogen-Activated Protein Kinase Phosphatases/metabolism , Mitogen-Activated Protein Kinase Phosphatases/genetics , Signal Transduction/physiology
13.
Front Immunol ; 15: 1409021, 2024.
Article in English | MEDLINE | ID: mdl-38751430

ABSTRACT

Chimeric antigen receptor-T (CAR-T) cell therapy has made remarkable strides in treating hematological malignancies. However, the widespread adoption of CAR-T cell therapy is hindered by several challenges. These include concerns about the long-term and complex manufacturing process, as well as efficacy factors such as tumor antigen escape, CAR-T cell exhaustion, and the immunosuppressive tumor microenvironment. Additionally, safety issues like the risk of secondary cancers post-treatment, on-target off-tumor toxicity, and immune effector responses triggered by CAR-T cells are significant considerations. To address these obstacles, researchers have explored various strategies, including allogeneic universal CAR-T cell development, infusion of non-activated quiescent T cells within a 24-hour period, and in vivo induction of CAR-T cells. This review comprehensively examines the clinical challenges of CAR-T cell therapy and outlines strategies to overcome them, aiming to chart pathways beyond its current Achilles heels.


Subject(s)
Cell- and Tissue-Based Therapy , Immunotherapy, Adoptive , Receptors, Chimeric Antigen , T-Lymphocytes , Animals , Humans , Antigens, Neoplasm/immunology , Hematologic Neoplasms/therapy , Hematologic Neoplasms/immunology , Immunotherapy, Adoptive/methods , Immunotherapy, Adoptive/adverse effects , Receptors, Antigen, T-Cell/immunology , Receptors, Chimeric Antigen/immunology , Receptors, Chimeric Antigen/genetics , T-Lymphocytes/immunology , T-Lymphocytes/transplantation , Tumor Microenvironment/immunology
14.
Eur J Med Chem ; 273: 116519, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38795519

ABSTRACT

Anticancer peptides (ACPs) have regarded as a new generation of promising antitumor drugs due to the unique mode of action. The main challenge is to develop potential anticancer peptides with satisfied antitumor activity and low toxicity. Here, a series of new α-helical anticancer peptides were designed and synthesized based on the regular repeat motif KLLK. The optimal peptides 14E and 14Aad were successfully derived from the new short α-helical peptide KL-8. Our results demonstrated that 14E and 14Aad had good antitumor activity and low toxicity, exhibiting excellent selectivity index. This result highlighted that the desirable modification position and appropriate hydrophobic side-chain structure of acidic amino acids played critical roles in regulating the antitumor activity/toxicity of new peptides. Further studies indicated that they could induce tumor cell death via the multiple actions of efficient membrane disruption and intracellular mechanisms, displaying apparent superiority in combination with PTX. In addition, the new peptides 14E and 14Aad showed excellent antitumor efficacy in vivo and low toxicity in mice compared to KL-8 and PTX. Particularly, 14Aad with the longer side chain at the 14th site exhibited the best therapeutic performance. In conclusion, our work provided a new avenue to develop promising anticancer peptides with good selectivity for tumor therapy.


Subject(s)
Antineoplastic Agents , Cell Proliferation , Drug Design , Drug Screening Assays, Antitumor , Peptides , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Animals , Humans , Mice , Peptides/chemistry , Peptides/pharmacology , Peptides/chemical synthesis , Structure-Activity Relationship , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Molecular Structure , Cell Line, Tumor , Mice, Inbred BALB C , Apoptosis/drug effects , Female
15.
Toxicology ; 505: 153841, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38796053

ABSTRACT

Paclobutrazol (PBZ) is a plant growth regulator that can delay plant growth and improve plant resistance and yield. Although it has been widely used in the growth of medicinal plants, human beings may take it by taking traditional Chinese medicine. There are no published studies on PBZ exposure in humans or standardized limits for PBZ in medicinal plants. We measured the solubility, oil-water partition coefficient (logP), and pharmacokinetics of PBZ in rats and established a physiologically based pharmacokinetic (PBPK) model of PBZ in rats. This was followed by extrapolation to healthy Chinese adult males as a theoretical foundation for future risk assessment of PBZ. The results showed that PBZ had low solubility and high fat solubility. Pharmacokinetic experiments showed that PBZ was absorbed rapidly but eliminated slowly in rats. On this basis, the rat PBPK model was successfully constructed and extrapolated to healthy Chinese adult males to predict the plasma concentration-time curve and exposure of PBZ in humans. The construction of the PBPK model of PBZ in this study facilitates the determination of the standard formulation limits and risk assessment of PBZ residues in medicinal plants.


Subject(s)
Models, Biological , Rats, Sprague-Dawley , Triazoles , Male , Animals , Triazoles/pharmacokinetics , Triazoles/blood , Humans , Rats , Plant Growth Regulators/pharmacokinetics , Adult , Solubility , Risk Assessment
16.
PLoS Biol ; 22(5): e3002195, 2024 May.
Article in English | MEDLINE | ID: mdl-38754078

ABSTRACT

People tend to intervene in others' injustices by either punishing the transgressor or helping the victim. Injustice events often occur under stressful circumstances. However, how acute stress affects a third party's intervention in injustice events remains open. Here, we show a stress-induced shift in third parties' willingness to engage in help instead of punishment by acting on emotional salience and central-executive and theory-of-mind networks. Acute stress decreased the third party's willingness to punish the violator and the severity of the punishment and increased their willingness to help the victim. Computational modeling revealed a shift in preference of justice recovery from punishment the offender toward help the victim under stress. This finding is consistent with the increased dorsolateral prefrontal engagement observed with higher amygdala activity and greater connectivity with the ventromedial prefrontal cortex in the stress group. A brain connectivity theory-of-mind network predicted stress-induced justice recovery in punishment. Our findings suggest a neurocomputational mechanism of how acute stress reshapes third parties' decisions by reallocating neural resources in emotional, executive, and mentalizing networks to inhibit punishment bias and decrease punishment severity.


Subject(s)
Punishment , Stress, Psychological , Humans , Punishment/psychology , Male , Stress, Psychological/physiopathology , Stress, Psychological/psychology , Female , Adult , Young Adult , Prefrontal Cortex/physiology , Prefrontal Cortex/physiopathology , Emotions/physiology , Social Justice , Brain/physiology , Magnetic Resonance Imaging
17.
Commun Biol ; 7(1): 517, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38693344

ABSTRACT

How does the human brain construct cognitive maps for decision-making and inference? Here, we conduct an fMRI study on a navigation task in multidimensional abstract spaces. Using a deep neural network model, we assess learning levels and categorized paths into exploration and exploitation stages. Univariate analyses show higher activation in the bilateral hippocampus and lateral prefrontal cortex during exploration, positively associated with learning level and response accuracy. Conversely, the bilateral orbitofrontal cortex (OFC) and retrosplenial cortex show higher activation during exploitation, negatively associated with learning level and response accuracy. Representational similarity analysis show that the hippocampus, entorhinal cortex, and OFC more accurately represent destinations in exploitation than exploration stages. These findings highlight the collaboration between the medial temporal lobe and prefrontal cortex in learning abstract space structures. The hippocampus may be involved in spatial memory formation and representation, while the OFC integrates sensory information for decision-making in multidimensional abstract spaces.


Subject(s)
Cognition , Hippocampus , Magnetic Resonance Imaging , Prefrontal Cortex , Humans , Hippocampus/physiology , Hippocampus/diagnostic imaging , Male , Prefrontal Cortex/physiology , Prefrontal Cortex/diagnostic imaging , Female , Cognition/physiology , Adult , Young Adult , Brain Mapping/methods , Decision Making/physiology
18.
Adv Mater ; : e2400115, 2024 May 16.
Article in English | MEDLINE | ID: mdl-38752837

ABSTRACT

All-solid-state lithium metal batteries (ASSLMBs) are considered as the most promising candidates for the next-generation high-safety batteries. To achieve high energy density in ASSLMBs, it is essential that the solid-state electrolytes (SSEs) are lightweight, thin, and possess superior electrochemical stability. In this study, a feasible and scalable fabrication approach to construct 3D supporting skeleton using an electro-blown spinning technique is proposed. This skeleton not only enhances the mechanical strength but also hinders the migration of Li-salt anions, improving the lithium-ion transference number of the SSE. This provides a homogeneous distribution of Li-ion flux and local current density, promoting uniform Li deposition. As a result, based on the mechanically robust and thin SSEs, the Li symmetric cells show outstanding Li plating/stripping reversibility. Besides, a stable interface contact between SSE and Li anode has been established with the formation of an F-enriched solid electrolyte interface layer. The solid-state Li|sulfurized polyacrylonitrile (Li|SPAN) cell achieves a capacity retention ratio of 94.0% after 350 cycles at 0.5 C. Also, the high-voltage Li|LCO cell shows a capacity retention of 92.4% at 0.5 C after 500 cycles. This fabrication approach for SSEs is applicable for commercially large-scale production and application in high-energy-density and high-safety ASSLMBs.

19.
Spectrochim Acta A Mol Biomol Spectrosc ; 315: 124236, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38615415

ABSTRACT

In this work, a colorimetric aptasensor based on magnetic beads (MBs), gold nanoparticles (AuNPs) and Horseradish Peroxidase (HRP) was prepared for the detection of mucin 1 (MUC1). Complementary DNA of the MUC1 aptamer (Apt) immobilized on the MBs was combined with the prepared AuNPs-Apt-HRP complex (AuNPs@Apt-HRP). In the presence of MUC1, it specifically bound to Apt, resulting in the detachment of gold nanoparticles from the MBs. After magnetic separation, AuNPs@Apt-HRP was separated into the supernatant and reacted with 3,3',5,5'-Tetramethylbenzidine (TMB) to produce color reaction from colorless to blue. The linear range of MUC1 was from 75 to 500 µg/mL (R2 = 0.9878), and the detection limit was 41.95 µg/mL. The recovery rate of MUC1 in human serum was 99.18 %∼101.15 %. This method is simple and convenient. Moreover, it does not require complex and expensive equipment for detection of MUC1. It provides value for the development of MUC1 colorimetric sensors and a promising strategy for the determination of MUC1 in clinical diagnosis.


Subject(s)
Aptamers, Nucleotide , Benzidines , Biosensing Techniques , Colorimetry , Gold , Limit of Detection , Metal Nanoparticles , Mucin-1 , Mucin-1/analysis , Mucin-1/blood , Colorimetry/methods , Gold/chemistry , Aptamers, Nucleotide/chemistry , Metal Nanoparticles/chemistry , Humans , Biosensing Techniques/methods , Horseradish Peroxidase/chemistry , Horseradish Peroxidase/metabolism
20.
Materials (Basel) ; 17(3)2024 Feb 02.
Article in English | MEDLINE | ID: mdl-38591593

ABSTRACT

To solve problems in dissimilarly light metal joints, refilled friction stir spot welding (RFSSW) is proposed instead of resistance spot welding. However, rotation speed, dwell time, plunge depth, and the diameter of welding tools all have a great influence on joints, which brings great challenges in optimizing welding parameters to ensure their mechanical properties. In this study, the 1.5 mm thick 2A12Al and 2 mm thick 7B04Al lap joints were prepared by Taguchi orthogonal experiment design and RFSSW. The welding tool (shoulder) diameters were 5 mm and 7 mm, respectively. The macro/microstructures of the cross-section, the geometrical characteristics of the effective welding depth (EWD), the stir zone area (SZA), and the stir zone volume (SZV) were characterized. The shear strength and failure mode of the lap joint were analyzed using an optical microscope. It was found that EWD, SZA, and SZV had a good correlation with tensile-shear force. The optimal welding parameters of 5 mm diameter joints are 1500 rpm of rotation speed, 2.5 mm of plunge depth, and 0 s of dwell time, which for 7 mm joints are 1200 rpm, 1.5 mm, and 2 s. The tensile-shear force of 5 mm and 7 mm joints welded with these optical parameters was 4965 N and 5920 N, respectively. At the same time, the 5 mm diameter joints had better strength and strength stability.

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