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1.
Cell Mol Life Sci ; 81(1): 205, 2024 May 04.
Article in English | MEDLINE | ID: mdl-38703204

ABSTRACT

BACKGROUND: Exposure to chronic psychological stress (CPS) is a risk factor for thrombotic cardiocerebrovascular diseases (CCVDs). The expression and activity of the cysteine cathepsin K (CTSK) are upregulated in stressed cardiovascular tissues, and we investigated whether CTSK is involved in chronic stress-related thrombosis, focusing on stress serum-induced endothelial apoptosis. METHODS AND RESULTS: Eight-week-old wild-type male mice (CTSK+/+) randomly divided to non-stress and 3-week restraint stress groups received a left carotid artery iron chloride3 (FeCl3)-induced thrombosis injury for biological and morphological evaluations at specific timepoints. On day 21 post-stress/injury, the stress had enhanced the arterial thrombi weights and lengths, in addition to harmful alterations of plasma ADAMTS13, von Willebrand factor, and plasminogen activation inhibitor-1, plus injured-artery endothelial loss and CTSK protein/mRNA expression. The stressed CTSK+/+ mice had increased levels of injured arterial cleaved Notch1, Hes1, cleaved caspase8, matrix metalloproteinase-9/-2, angiotensin type 1 receptor, galactin3, p16IN4A, p22phox, gp91phox, intracellular adhesion molecule-1, TNF-α, MCP-1, and TLR-4 proteins and/or genes. Pharmacological and genetic inhibitions of CTSK ameliorated the stress-induced thrombus formation and the observed molecular and morphological changes. In cultured HUVECs, CTSK overexpression and silencing respectively increased and mitigated stressed-serum- and H2O2-induced apoptosis associated with apoptosis-related protein changes. Recombinant human CTSK degraded γ-secretase substrate in a dose-dependent manor and activated Notch1 and Hes1 expression upregulation. CONCLUSIONS: CTSK appeared to contribute to stress-related thrombosis in mice subjected to FeCl3 stress, possibly via the modulation of vascular inflammation, oxidative production and apoptosis, suggesting that CTSK could be an effective therapeutic target for CPS-related thrombotic events in patients with CCVDs.


Subject(s)
Apoptosis , Cathepsin K , Chlorides , Disease Models, Animal , Ferric Compounds , Thrombosis , Animals , Humans , Male , Mice , ADAMTS13 Protein/metabolism , ADAMTS13 Protein/genetics , Cathepsin K/metabolism , Cathepsin K/genetics , Chlorides/metabolism , Human Umbilical Vein Endothelial Cells/metabolism , Mice, Inbred C57BL , Mice, Knockout , Plasminogen Activator Inhibitor 1/metabolism , Plasminogen Activator Inhibitor 1/genetics , Stress, Psychological/complications , Stress, Psychological/metabolism , Thrombosis/metabolism , Thrombosis/pathology , Transcription Factor HES-1/metabolism , Transcription Factor HES-1/genetics
2.
J Colloid Interface Sci ; 668: 634-645, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-38696991

ABSTRACT

Solid polymer electrolytes (SPEs) have been considered the most promising separators for all-solid-state lithium metal batteries (ASSLMBs) due to their ease of processing and low cost. However, the practical applications of SPEs in ASSLMBs are limited by their low ionic conductivities and mechanical strength. Herein, we developed a three-dimensional (3D) interconnected MXene (Ti3C2Tx) network and Li6.4La3Zr1.4Ta0.6O12 (LLZTO) particles synergistically reinforced polyethylene oxide (PEO)-based SPE, where the association of Li+ with ether-oxygen in PEO could be significantly weakened through the Lewis acid-base interactions between the electron-absorbing group (Ti-F, -O-) of Ti3C2Tx and Li+. Besides, the TFSI- in lithium salts could be immobilized by hydrogen bonds from the Ti-OH of Ti3C2Tx. The 3D interconnected Ti3C2Tx network not only alleviated the agglomeration of inorganic fillers (LLZTO), but also improved the mechanical strength of composite solid electrolyte (CSE). Consequently, the assembled Li||CSE||Li symmetric battery showed excellent cycling stability at 35 ℃ (stable cycling over 3000 h at 0.1 mA cm-2, 0.1 mAh cm-2) and -2 ℃ (stable cycling over 2500 h at 0.05 mA cm-2, 0.05 mAh cm-2). Impressively, the LiFePO4||CSE||Li battery showed a high discharge capacity of 145.3 mAh/g at 0.3 C after 300 cycles at 35 ℃. This rational structural design provided a new strategy for the preparation of high-performance solid-state electrolytes for lithium metal batteries.

3.
Microorganisms ; 12(5)2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38792726

ABSTRACT

Fire blight, a devastating disease caused by Erwinia amylovora, poses a significant threat to pear and apple trees in Xinjiang province, China. In an effort to combat this pathogen, we isolated 10 bacteria from various components of apple and crabapple trees and conducted screenings to assess their ability to inhibit E. amylovora in vitro. Through biochemical tests and partial 16S rRNA gene sequencing, we identified two promising strains, Priestia megaterium strain H1 and Bacillus subtilis strain I2. These strains were then evaluated for their efficacy in biocontrol under controlled laboratory conditions, focusing on immature fruits and leaves. Remarkably, all selected antagonists exhibited the capability to reduce the severity of the disease on both fruit and leaves. P. megaterium strain H1 and B. subtilis strain I2 exhibited significant reductions in disease incidence on both immature fruits and leaves compared to the control. Specifically, on immature fruits, they achieved reductions of 53.39% and 44.76%, respectively, while on leaves, they demonstrated reductions of 59.55% and 55.53%, respectively. Furthermore, during the study, we detected the presence of lipopeptides, including surfactin, iturins, bacillomycin D, and fengycins, in the methanol extract obtained from these two antagonistic bacteria using thin-layer chromatography (TLC). Based on the results obtained, B. subtilis strain I2 and P. megaterium strain H1 exhibit considerable potential for controlling fire blight. However, further evaluation of their efficacy under natural field conditions is essential to validate their practicality as a biocontrol method.

4.
J Glob Health ; 14: 04060, 2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38665062

ABSTRACT

Background: The nature of the relationship between red meat consumption and nonalcoholic fatty liver disease (NAFLD) remains unclear. Through this meta-analysis, we aimed to determine the association and dose-response relationship between red meat consumption (both processed and unprocessed) and the risk of NAFLD. Methods: We systematically searched CENTRAL, PubMed, Embase, Web of Science and Scopus from inception to February 2022 for observational studies in which the exposure of interest was red meat consumption; the outcome of interest was the risk of NAFLD; and where odds ratios (ORs) or risk ratios were provided or could be calculated. We used random-effects meta-analyses to pool the effect sizes and performed analyses to estimate the linearity of the dose-response relationships between red meat intake and NAFLD risk. Results: We included 10 studies in this review. The meta-analysis showed a significant association between the intake of red meat (OR = 1.27; 95% confidence interval (CI) = 1.07-1.50, P = 0.000, I2 = 81%), processed red meat (OR = 1.20; 95% CI = 1.04-1.3, P = 0.162, I2 = 34.9%) or unprocessed red meat (OR = 1.28; 95% CI = 1.05-1.55, P = 0.001, I2 = 76.2%) and the risk of NAFLD. We also found a significant linear dose-response association between processed red meat intake and NAFLD, with each 25-g increment of processed red meat intake per day was associated with an 11.1% higher risk of NAFLD (OR = 1.11; 95% CI = 1.01-1.22, P = 0.029), and a nonlinear association between unprocessed meat intake and NAFLD (P = 0.003 for nonlinearity). Conclusions: Our findings indicate a potential positive association between red meat consumption (both processed and unprocessed) and NAFLD risk, especially in relation to increased intake of processed red meat compared to unprocessed red meat. However, caution is advised in interpreting these results; further research could establish a clearer understanding of the relationship between red meat consumption and NAFLD risk. Registration: PROSPERO: CRD42022332839.


Subject(s)
Non-alcoholic Fatty Liver Disease , Red Meat , Non-alcoholic Fatty Liver Disease/epidemiology , Non-alcoholic Fatty Liver Disease/etiology , Humans , Red Meat/adverse effects , Meat Products/adverse effects , Risk Factors , Food Handling
5.
Infection ; 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38568411

ABSTRACT

PURPOSE: To evaluate the efficacy and safety of oral ibrexafungerp (HS-10366) versus placebo in Chinese patients with vulvovaginal candidiasis (VVC). METHODS: A double-blind, placebo-controlled, randomized, multicenter phase III study was conducted in symptomatic VVC patients. Patients received (2:1) twice-daily oral ibrexafungerp 300 mg or matching placebo for 1 day. The primary endpoint was clinical cure (vulvovaginal signs and symptoms [VSS] score = 0) at test-of-cure (TOC) on day 11 ± 3. The secondary endpoints included mycological eradication, overall response, and clinical improvement (VSS score ≤ 1) at TOC, and vulvovaginal symptom resolution at follow-up on day 25 ± 4. RESULTS: In total, 360 patients were included in the modified intention-to-treat set (defined as positive Candida cultured and receiving at least one study drug; 239 for ibrexafungerp, 121 for placebo). Compared with placebo, patients receiving ibrexafungerp had a significantly higher proportion of clinical cure (51.0% vs. 25.6%), mycological eradication (55.6% vs. 18.2%), overall response (33.9%, vs. 8.3%) at TOC and complete symptom resolution (74.5% vs. 39.7%, all P < 0.001) at follow-up. Subgroup analysis of clinical cure indicated that patients with C. albicans could benefit from ibrexafungerp over placebo. A similar benefit trend was also observed in those with non-albicans Candida by post-hoc analysis. Further analyses revealed similar efficacy of ibrexafungerp between patients with fluconazole non-susceptible C. albicans and fluconazole susceptible C. albicans regarding clinical cure and mycological eradication. Ibrexafungerp was generally well tolerated. Adverse events were primarily gastrointestinal and were mainly mild in severity. CONCLUSIONS: As a first-in-class antifungal agent, ibrexafungerp demonstrated promising efficacy and favorable safety for VVC treatment in Chinese patients. CHINADRUGTRIALS.ORG. CN REGISTRY NUMBER: CTR20220918.

6.
Pathol Oncol Res ; 30: 1611376, 2024.
Article in English | MEDLINE | ID: mdl-38572338

ABSTRACT

Mammary-like vulvar adenocarcinoma (MLVA) is an exceedingly rare subtype of vulvar adenocarcinoma that shares features with mammary gland tissue. Due to its rarity and lack of consensus, MLVA presents diagnostic challenges to pathologists. We present the case of a 59-year-old female with an ulcerated mass on the right side of the external genitalia, diagnosed as MLVA. Comprehensive immunohistochemistry (IHC) and gene sequencing studies were performed to characterize the tumor. IHC analysis revealed triple expression of hormonal receptors (estrogen receptor, progesterone receptor, and HER2), supporting the mammary gland origin of the tumor. Gene sequencing identified unique genetic mutations associated with the expression of hormonal markers. One fusion gene (ERBB2-NAGLU) has not been reported in any tumors, and other mutations with unique mutation types have not been previously reported in MLVA. Our findings shed light on the molecular characteristics of MLV and may help improve the diagnosis and treatment of this rare type of vulvar adenocarcinoma.


Subject(s)
Adenocarcinoma , Mammary Glands, Human , Vulvar Neoplasms , Female , Humans , Middle Aged , Mammary Glands, Human/metabolism , Mammary Glands, Human/pathology , Adenocarcinoma/pathology , Vulvar Neoplasms/genetics , Vulvar Neoplasms/metabolism , Vulvar Neoplasms/pathology , Breast/pathology , High-Throughput Nucleotide Sequencing
7.
J Texture Stud ; 55(2): e12830, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38581175

ABSTRACT

Freezing and blanching are essential processing steps in the production of frozen yellow peaches, inevitably leading to texture softening of the fruit. In this study, the synergistic mechanism of stem blanching, freezing conditions (-20°C, -40°C, -80°C, and liquid nitrogen [-173°C]), and sample sizes (cubes, slices, and half peaches) on macroscopic properties of texture, cellular structure, and ice crystal size distribution of frozen yellow peaches were measured. Blanching enhanced the heat and mass transfer rates in the subsequent freezing process. For nonblanched samples, cell membrane integrity was lost at any freezing rate, causing a significant reduction in textural quality. Slow freezing further exacerbated the texture softening, while the ultra-rapid freezing caused structural rupture. For blanched samples, the half peaches softened the most. The water holding capacity and fracture stress were not significantly affected by changes in freezing rate, although the ice crystal size distribution was more susceptible to the freezing rate. Peach cubes that had undergone blanching and rapid freezing (-80°C) experienced 4% less drip loss than nonblanched samples. However, blanching softened yellow peaches more than any freezing conditions. The implementation of uniform and shorter duration blanching, along with rapid freezing, has been proven to be more effective in preserving the texture of frozen yellow peaches. Optimization of the blanching process may be more important than increasing the freezing rate to improve the textural quality of frozen yellow peaches.


Subject(s)
Prunus persica , Steam , Freezing , Food Preservation , Ice
8.
Mol Genet Genomic Med ; 12(3): e2409, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38511267

ABSTRACT

BACKGROUND: Congenital myasthenic syndrome is a heterogeneous group of inherited neuromuscular transmission disorders. Variants in RAPSN are a common cause of CMS, accounting for approximately 14%-27% of all CMS cases. Whether preimplantation genetic testing for monogenic disease (PGT-M) could be used to prevent the potential birth of CMS-affected children is unclear. METHODS: Application of WES (whole-exome sequencing) for carrier testing and guidance for the PGT-M in the absence of a genetically characterized index patient as well as assisted reproductive technology were employed to prevent the occurrence of birth defects in subsequent pregnancy. The clinical phenotypes of stillborn fetuses were also assessed. RESULTS: The family carried two likely pathogenic variants in RAPSN(NM_005055.5): c.133G>A (p.V45M) and c.280G>A (p.E94K). And the potential birth of CMS-affected child was successfully prevented, allowing the family to have offspring devoid of disease-associated variants and exhibiting a normal phenotype. CONCLUSION: This report constitutes the first documented case of achieving a CMS-free offspring through PGT-M in a CMS-affected family. By broadening the known variant spectrum of RAPSN in the Chinese population, our findings underscore the feasibility and effectiveness of PGT-M for preventing CMS, offering valuable insights for similarly affected families.


Subject(s)
Myasthenic Syndromes, Congenital , Child , Female , Pregnancy , Humans , Myasthenic Syndromes, Congenital/diagnosis , Myasthenic Syndromes, Congenital/genetics , Genetic Testing , Phenotype
9.
Hum Pathol ; 145: 86-94, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38431056

ABSTRACT

OBJECTIVES: To explore the clinicopathologic features, treatment, and survival outcomes of angioimmunoblastic T-cell lymphoma (AITL) involving the nasopharynx. METHODS: We retrospectively analyzed 73 cases of AITL. Among them, 64 cases with complete pre-treatment 18F-FDG positron emission tomography/computed tomography (PET/CT) images were integrated into the analysis of clinical characteristics and PET/CT findings of AITL involving the nasopharynx; 14 cases with both biopsies from lymph node and nasopharynx were included in the comparison of pathological characteristics of AITL in the two areas. Forty-six of the 73 patients who received first-line systemic treatment at our institute were included in the treatment efficacy and survival analyses. RESULTS: Nasopharyngeal involvement was seen in 44/64 (68.8%) patients. Histologically, lymph node and nasopharyngeal biopsies in 14 patients both showed small to medium-sized tumor cells, complex inflammatory infiltration, and Reed-Sternberg-like cells or B immunoblasts. However, tumor cells with clear cytoplasm, significant high endothelial venule (HEV) hyperplasia, and perivascular infiltration were observed in 5/14, 3/14, and 2/14 nasopharyngeal biopsies, respectively, but in all fourteen lymph node biopsies (P < 0.05). Immunophenotypic profiles and gene rearrangements were highly concordant. Treatment efficacy and survival were similar between patients with nasopharyngeal involvement and those without (P > 0.05), indicating nasopharyngeal involvement is not a prognostic factor for AITL patients. CONCLUSIONS: Nasopharyngeal involvement is common in AITL but can be easily misdiagnosed because of its atypical pathologic pattern, especially when a lymph node biopsy is unavailable. However, the patient's clinical presentation, PET/CT manifestations, the typical immunophenotype, and gene rearrangements help the diagnosis.


Subject(s)
Immunoblastic Lymphadenopathy , Lymphoma, T-Cell , Humans , Positron Emission Tomography Computed Tomography , Retrospective Studies , Immunoblastic Lymphadenopathy/genetics , Immunoblastic Lymphadenopathy/pathology , Lymphoma, T-Cell/diagnosis , Lymphoma, T-Cell/genetics , Lymphoma, T-Cell/pathology , Nasopharynx/pathology , Diagnostic Errors
10.
J Assist Reprod Genet ; 41(4): 929-938, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38386120

ABSTRACT

PURPOSE: This prospective study investigates the correlation between vaginal microecology and pregnancy outcomes and explores their impact on endometrial microbiota composition during frozen embryo transfer (FET) cycles. Additionally, the impact of transvaginal Lactobacillus supplementation on reproductive outcomes in patients with previous failed cycles was assessed. METHODS: A total of 379 patients undergoing FET at a reproductive medicine center were categorized into clinical pregnancy (CP), miscarriage (MISC), and non-pregnant (NP) groups. Vaginal specimens were collected for microecological evaluation prior to embryo transfer. Endometrial microbiota samples were obtained during embryo transfer for 16S rRNA gene sequencing analysis to assess endometrial microbiota composition. Vaginal microecological indicators, including pH, Lactobacillus dominance, and leukocyte esterase activity, were measured. Transvaginal Lactobacillus supplementation was investigated in 60 patients with previous failed cycles. RESULTS: Vaginal microecology significantly correlated with pregnancy outcomes, with normal microecology associated with a higher clinical pregnancy rate. Vaginal pH and leukocyte esterase activity were significantly associated with clinical pregnancy. Furthermore, vaginal microecological differences significantly impacted endometrial microbiota composition. However, no significant differences were observed in endometrial microbiota composition among the CP, MISC, and NP groups. Notably, transvaginal Lactobacillus supplementation increased the clinical pregnancy rate without affecting the miscarriage rate. CONCLUSION: This study highlights that normal vaginal microecology, characterized by lower pH and leukocyte esterase negativity, is associated with a higher likelihood of clinical pregnancy following FET. Importantly, vaginal microecological differences influence endometrial microbiota composition. Moreover, transvaginal Lactobacillus supplementation appears promising in improving clinical pregnancy rates in patients with previous failed cycles. These findings contribute to a better understanding of the interplay between vaginal and endometrial microbiota and offer potential interventions to enhance reproductive success in assisted reproductive technologies.


Subject(s)
Embryo Transfer , Endometrium , Microbiota , Pregnancy Outcome , Vagina , Humans , Female , Pregnancy , Adult , Embryo Transfer/methods , Microbiota/genetics , Vagina/microbiology , Endometrium/microbiology , Endometrium/pathology , Pregnancy Rate , Prospective Studies , Cryopreservation/methods , Lactobacillus/isolation & purification , Lactobacillus/genetics , Abortion, Spontaneous/microbiology , Fertilization in Vitro/methods
11.
Clin Chim Acta ; 555: 117794, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38341017

ABSTRACT

Trisomy 8 syndrome, also known as " Warkany syndrome type 2 ", was first reported in 1971. Complete trisomy 8 are mostly aborted spontaneouslyinthe first trimester. Trisomy 8 mosaicism (T8M), predominated in the current cases reported. Itisahighlyheterogeneous Chromosome disorder. We know little about its effects on fertility. In this case, a patient with T8M combined with phenylketonuria was diagnosed. She's mentally retarded. After evaluating the anatomy and function of the reproductive system, the patient conceived through preimplantationgenetictesting-intracytoplasmicsperminjection-embryotransfer (PGT-ICSI-ET) and obtained a healthy fetus, which is the first report. The study focuses on the maintenance of fertility in patients with T8M, the effects of phenylketonuria and genetic counseling.


Subject(s)
Phenylketonurias , Trisomy , Female , Humans , Trisomy/genetics , Uniparental Disomy/genetics , Phenylketonurias/complications , Phenylketonurias/diagnosis , Phenylketonurias/genetics , Chromosomes, Human, Pair 8 , Mosaicism
12.
Food Sci Nutr ; 12(1): 459-470, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38268911

ABSTRACT

Depression is a global public health issue that is widely studied due to the large number of people it affects and its serious consequences. Clinical studies have shown that regular tea consumption may reduce depression risk. (-)-Epigallocatechin gallate (EGCG), the main tea polyphenol, was observed to alleviate depression, but the underlying mechanism has not been elucidated. In this study, chronic unpredictable mild stress (CUMS) was used to induce depression-like behavior in mice, and behavioral tests, such as sucrose preference test and forced swim test, were performed. Then, ELISA, western blot and QT-PCR tests were used to assess the expression of the key components of the NLRP3 inflammasome and its downstream inflammatory effectors (e.g., IL-1ß, IL-18), autophagy markers (Beclin-1, LC3, P62) and apoptosis markers (Bax, Bcl-2) in mouse brain tissues. Changes in serum lipid levels were also assessed. EGCG alleviated CUMS-induced depression-like behavioral changes in mice, reduced activation of the NLRP3 inflammasome, inhibited the mTOR signaling pathway, restored autophagy levels, reduced apoptosis marker expression and attenuated abnormal changes in blood lipid levels. Our study demonstrates that EGCG exerts antidepressive effects through multiple mechanisms, providing new insight into the pathological mechanism of depression and laying the foundation for the development of new therapeutic measures.

14.
Immunol Invest ; 53(2): 91-114, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37987679

ABSTRACT

The epithelial ovarian carcinoma (EOC) is one of leading causes of cancer-related mortality in females. For some patients, complete resection cannot be achieved, thus neoadjuvant chemotherapy (NACT) following interval debulking surgery (IDS) could be an alternative choice. In general-held belief, cytotoxic chemotherapy is assumed to be immunosuppressive, because of its toxicity to dividing cells in the bone marrow and peripheral lymphoid tissues. However, increasing evidence highlighted that the anticancer activity of chemotherapy may also be related to its ability to act as an immune modulator. NACT not only changed the morphology of cancer cells, but also changed the transcriptomic and genomic profile of EOC, induced proliferation of cancer stem-like cells, gene mutation, and tumor-related adaptive immune response. This review will provide a comprehensive overview of recent studies evaluating the impact of NACT on cancer cells and immune system of advanced EOC and their relationship to clinical outcome. This information could help us understand the change of immune system during NACT, which might provide new strategies in future investigation of immuno-therapy for maintenance treatment of EOC.


Subject(s)
Ovarian Neoplasms , Female , Humans , Carcinoma, Ovarian Epithelial/drug therapy , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/pathology , Neoadjuvant Therapy , Neoplasm Staging , Chemotherapy, Adjuvant , Immune System , Retrospective Studies
15.
iScience ; 26(12): 108433, 2023 Dec 15.
Article in English | MEDLINE | ID: mdl-38077123

ABSTRACT

Considering the significance of multipath transmissions of respiratory pathogens in the post-epidemic era, surprisingly little is acknowledged regarding the susceptibility, short-term aerodynamics, and exposure risk of children in indoor environments. Here, experimental and computational investigations were conducted to evaluate the exposure risks associated with respiratory pathogens. The dominant effect of recirculation structure originating from indoor ventilation, including air supply modes and air change rate, on aerosol dispersion was quantitatively proved. A large proportion of deposited aerosol particles was captured by the human body, and deposited particles may further increase under high air change rate, which required a balanced ventilation strategy. Little discrepancies existed between adults and children in exposure risk by airborne transmission. The infection probability by contact transmission for children, however, may be surprisingly high due to high frequency in interactive activities, deposition on upper and lower limbs of accompanying parents, and the wall within arm span.

16.
Cancers (Basel) ; 15(23)2023 Dec 03.
Article in English | MEDLINE | ID: mdl-38067399

ABSTRACT

Chronic Myelogenous Leukemia (CML) is a prevalent hematologic malignancy characterized by the malignant transformation of myeloid cells and their proliferation in the peripheral blood. The management of CML poses significant challenges, particularly in detecting and eradicating minimal residual disease, which is crucial for preventing relapse and improving survival outcomes. Traditional minimal residual disease detection methods, such as bone marrow aspiration, are invasive and have limitations which include the potential for sampling errors and false negatives. This study introduces a novel label-free microfluidic chip designed for the segregation and recovery of circulating leukemia cells, offering a non-invasive liquid biopsy approach with potential applications in precision medicine. Over July 2021 to October 2023, we recruited 56 CML patients across various disease stages and collected blood samples for analysis using our microfluidic device. The device demonstrated high efficacy in isolating circulating leukemia cells, with an optimal capture efficiency of 78% at a sample flow rate of 3 mL/h. Our results indicate that the microfluidic device can efficiently segregate and quantify circulating leukemia cells, providing a detailed understanding of CML progression and treatment response. The significant reduction in circulating leukemia cell counts in patients in complete remission highlights the device's potential in monitoring treatment efficacy. Furthermore, the device's sensitivity in detecting minimal residual disease could offer a more reliable prognostic tool for therapeutic decision-making in CML management.

17.
Biomed Microdevices ; 26(1): 3, 2023 12 12.
Article in English | MEDLINE | ID: mdl-38085348

ABSTRACT

We present a label-free microfluidic chip for the segregation of circulating leukemia cells (CLCs) from blood samples, with a focus on its clinical applications in Acute Myeloid Leukemia (AML). The microfluidic chip achieved an approximate capture efficiency of 92%. The study analyzed a comprehensive set of 66 blood specimens from AML patients in different disease stages, including newly diagnosed and relapsing cases, patients in complete remission, and those in partial remission. The results showed a significant difference in CLC counts between active disease stages and remission stages (p < 0.0001), with a proposed threshold of 5 CLCs to differentiate between the two. The microfluidic chip exhibited a sensitivity of 95.4% and specificity of 100% in predicting disease recurrence. Additionally, the captured CLCs were subjected to downstream molecular analysis using droplet digital PCR, allowing for the identification of genetic mutations associated with AML. Comparative analysis with bone marrow aspirate processing by FACS demonstrated the reliability and accuracy of the microfluidic chip in tracking disease burden, with highly agreement results obtained between the two methods. The non-invasive nature of the microfluidic chip and its ability to provide real-time insights into disease progression make it a promising tool for the proactive monitoring and personalized patient care of AML.


Subject(s)
Leukemia, Myeloid, Acute , Microfluidics , Humans , Reproducibility of Results , Leukemia, Myeloid, Acute/diagnosis , Leukemia, Myeloid, Acute/genetics , Polymerase Chain Reaction , Mutation , Prognosis
18.
Int Immunopharmacol ; 124(Pt B): 111060, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37862738

ABSTRACT

Tuberculosis poses a significant threat to human health due to the lack of an effective vaccine. Although promising progress has been made in the development of tuberculosis vaccines, new vaccines that broaden the antigenic repertoire need to be developed to eradicate this illness. In this study, we used Mycobacterium tuberculosis ferritin BfrB and heat-shock protein GrpE to construct a novel multi-antigenic fusion protein, BfrB-GrpE (BG). BG protein was stably overexpressed in the soluble form in Escherichia coli at a high yield and purified via sequential salt fractionation and hydrophobic chromatography. Purified BG was emulsified in an adjuvant containing N, N'-dimethyl-N, N'-dioctadecylammonium bromide, polyinosinic-polycytidylic acid, and cholesterol (DPC) to construct the BG/DPC vaccine, which stimulated strong cellular and humoral immune responses in mice. Moreover, combination of BG with our previously developed vaccine, Mtb10.4-HspX (MH), containing antigens from both the proliferating and dormant stages, significantly reduced the bacterial counts in the lungs and spleens of M. tuberculosis-infected mice. Importantly, mice that received BG + MH/DPC after M. tuberculosis H37Rv infection survived slightly better (100% survival) than those that received the BCG vaccine (80% survival), although the difference was not statistically significant. Our findings can aid in the selection of antigens and optimization of vaccination regimens to improve the efficacy of tuberculosis vaccines.


Subject(s)
Mycobacterium tuberculosis , Tuberculosis Vaccines , Tuberculosis , Animals , Mice , Humans , Antigens, Bacterial/genetics , Tuberculosis/prevention & control , BCG Vaccine , Vaccines, Subunit , Bacterial Proteins/genetics
19.
Adv Sci (Weinh) ; 10(31): e2304045, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37736679

ABSTRACT

Metallic glass, with its unique disordered atomic structure and high density of low-coordination sites, is regarded as the most competitive new catalyst for environmental catalysis. However, the efficiency and stability of metallic glass catalysts are often affected by their atomic configuration. Thus, the design and regulation of the nanoscale structure of metallic glasses to improve their catalytic efficiency and stability remains a challenge. Herein, a non-noble component, Fe75 P15 C10 amorphous ribbon, is used as a precursor to fabricate a hierarchical gradient catalyst with nanoscale heterogeneous and oxygenous amorphous structure by simple annealing and acid-immersing. The resulting catalyst offers an ultrahigh catalytic ability of kSA• C0 = 3101 mg m-2  min-1 and excellent reusability of 39 times without efficiency decay in dye wastewater degradation. Theoretical calculations indicate that the excellent catalytic performance of the catalyst can be attributed to its unique heterogeneous nanoglass structure, which induces oxygen atoms. Compared to the FePC structure, the FeP/FePCO structure exhibits strong charge transferability, and the energy barrier of the rate-determining steps of the conversion of S2 O8 2- to SO4 -• is reduced from 2.52 to 0.97 eV. This study reveals that a heterogeneous nanoglass structure is a new strategy for obtaining high catalytic performance.

20.
Front Psychol ; 14: 1187433, 2023.
Article in English | MEDLINE | ID: mdl-37457089

ABSTRACT

Background: Healthcare systems had an exceptionally difficult time during the early COVID-19 pandemic. Nurse managers in particular made enormous contributions to ensuring the safety of patients and front-line nurses while being under excessive psychological stress. However, little is known about their experiences during this time. Objective: The aim of this study was thus to assess the level of stress overload and psychological feelings of nurse managers during the early COVID-19 pandemic. Methods: A mixed methods sequential explanatory design study with non-random convenience sampling was performed, following the STROBE and COREQ checklists. The study was conducted at the Affiliated Dongyang Hospital, Wenzhou Medical University, with data collected from six provinces in southern China (Zhejiang, Hubei, Shanghai, Jiangsu, Hunan and Jiangxi) during March 2020 and June 2020. A total of 966 nurse managers completed the Stress Overload Scale and Work-Family Support Scale. In addition, a nested sample of nurse managers participated in semi-structured face-to-face interviews. The data were then analyzed using qualitative content analysis, Pearson correlation, and multiple linear regression. Results: The quantitative results showed that nurse managers experienced a moderate level of stress load. There was a significant negative correlation between work-family support and stress load (r = -0.551, p < 0.01). Concerns about protecting front-line nurses and work-family support were the main factors affecting the stress load, which accounted for 34.0% of the total variation. Qualitative analysis identified four main thematic analyses that explained stress load: (1) great responsibility and great stress, (2) unprecedented stress-induced stress response, (3) invisible stress: the unknown was even more frightening, and (4) stress relief from love and support. Taken together these findings indicate that concern about protecting front-line nurses and negative work-family support of nurse managers were the main factors causing stress overload. Conclusion: Implementing measures focused on individual psychological adjustment combined with community and family support and belongingness is one potential strategy to reduce psychological stress among nurse managers.

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