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2.
Infect Med (Beijing) ; 3(3): 100124, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39314804

ABSTRACT

Hand, foot, and mouth disease (HFMD) is a prevalent infectious affliction primarily affecting children, with a small portion of cases progressing to neurological complications. Notably, in a subset of severe HFMD cases, neurological manifestations may result in significant sequelae and pose a risk of mortality. We systematically conducted literature retrieval from the databases PubMed (1957-2023), Embase (1957-2023), and Web of Science (1957-2023), in addition to consulting authoritative guidelines. Subsequently, we rigorously selected the most relevant articles within the scope of this review for comprehensive analysis. It is widely recognized that the severity of HFMD is attributed to a multifaceted array of pathophysiological mechanisms. The implication of multi-system dysfunction appears to be perturbances of the human defense system; therefore, it contributes to the severity of HFMD. In this review, we provide an overview and analysis of recent insights into the molecular mechanisms contributing to the severity of HFMD, with a particular focus on cytokine release syndrome, the involvement of the renin-angiotensin system, regional immunity, endothelial dysfunction, catecholamine storm, viral invasion, and the molecular mechanisms of neurological damage. We speculate that the domino effect of diverse physiological systems, initiated by damage to the central nervous system, serve as the primary mechanisms governing the severity of HFMD. Simultaneously, we emphasize the knowledge gaps and research urgently required to delineate a quick roadmap for ongoing and essential studies on HFMD.

3.
Food Chem ; 463(Pt 2): 141291, 2024 Sep 16.
Article in English | MEDLINE | ID: mdl-39303466

ABSTRACT

In recent years, the biocompatibility and environmental friendliness of xylan-based materials have demonstrated great potential in the field of food packaging and coatings. In this study, the cationized xylan based composite coating (CXC) was developed using a hybrid system of cationic-modified bamboo xylan (CMX) and sodium alginate (SA) combined with thyme oil microcapsules (TM). The optimized CXC-B was composed of 1.27 % TM, 2.42 % CMX (CMX: SA = 3:2), and 96.31 % distilled water. When applied to the surface of a blueberry, the CXC-B treatment extended the ambient storage time of the fruit to 10 days while substantially reducing its morbidity (P < 0.05) and protecting its texture, flavor, and nutritional integrity. The resulting composite coating provides a promising solution to the problem of blueberry perishability during ambient storage.

4.
Clin Cancer Res ; : OF1-OF8, 2024 Sep 19.
Article in English | MEDLINE | ID: mdl-39297621

ABSTRACT

PURPOSE: Relapsed and/or refractory peripheral T-cell lymphoma (r/r PTCL) is an aggressive and heterogeneous hematologic malignancy with high unmet need. Previously, PI3K inhibitors were shown to be efficacious in B- and T-cell lymphomas, but as a drug class, these agents have frequently been observed to have tolerability limitations. Next-generation agents that improve the tolerability while maintaining efficacy are desirable. PATIENTS AND METHODS: A phase Ib clinical study was conducted with the oral PI3K-delta isoform-selective small-molecule inhibitor, linperlisib, in patients with r/r PTCL, and the clinical benefit was explored by the evaluation of safety and efficacy. RESULTS: In this clinical study, 43 patients with r/r PTCL in China were treated with continuous dosing of 80-mg linperlisib once a day. Treatment-related adverse events (AE) were manageable. The most frequently reported grade 3 AE were neutropenia (21%), pneumonia (11.6%), and hypertriglyceridemia (7%). All other AE were either absent or reported in <5% of the patients. Linperlisib treatment for these patients with r/r PTCL, consisting of the major PTCL subtypes, was observed to have a 60.5% overall response rate with 35% complete responses and led to a median duration of response of 11.1 months, median progression-free survival of 11.8 months, and a median overall survival of >38 months (not reached). CONCLUSIONS: With the very promising clinical activity against r/r PTCL, the results of this study support the further investigation of linperlisib for the treatment of r/r PTCL.

5.
Chin Med J (Engl) ; 2024 Sep 24.
Article in English | MEDLINE | ID: mdl-39313774

ABSTRACT

BACKGROUND: Lung cancer is the most common cancer and a leading cause of cancer-related deaths globally. The aim of this study was to evaluate the incidence and mortality of lung cancer worldwide in 2022 and to project the number of new cases and deaths due to lung cancer in China and the United States in 2050. METHODS: In this study, data from the GLOBCAN 2022 database were used to analyze lung cancer incidence and mortality. The current status of lung cancer incidence and deaths was described by country/region, sex, age, and the human development index (HDI), and future lung cancer incidence and deaths in China and the United States were projected for 2050. RESULTS: Globally, an estimated 2,480,675 new lung cancer cases and 1,817,469 lung cancer-related deaths occurred in 2022, with age-standardized incidence rates (ASIRs) and age-standardized mortality rates (ASMRs) of 23.6/100,000 and 16.8/100,000, respectively. In China, the ASIR and ASMR for male lung cancer patients were approximately 1.7 times and 2.7 times greater than those for female lung cancer patients, respectively. The ASIR and ASMR in high-HDI countries were approximately 8.5 times and 6.5 times those in low-HDI countries, respectively. It is estimated that in 2050, there will be approximately 1120 thousand new cases and 960 thousand deaths among Chinese men, 680 thousand new cases and 450 thousand deaths among Chinese women, approximately 170 thousand new cases and 110 thousand deaths among American men, and 160 thousand new cases and 90 thousand deaths among American women. CONCLUSIONS: There are significant differences in the incidence and mortality of lung cancer among different regions and sexes. Therefore, sex factors need to be considered in the prevention, screening, and treatment strategies of lung cancer, and the implementation of tertiary prevention measures for lung cancer, especially primary and secondary prevention, needs to be actively promoted.

6.
Transl Oncol ; 49: 102115, 2024 Nov.
Article in English | MEDLINE | ID: mdl-39217852

ABSTRACT

OBJECTIVE: To demonstrate the feasibility of using focused ultrasound to enhance delivery of PD-1 inhibitors in glioma rats and determine if such an approach increases treatment efficacy. METHODS: C6 glioma in situ rat model was used in this study. Transcranial irradiation with FUS combined with microbubbles was administered to open the blood-brain barrier (BBB). The efficacy of BBB opening was evaluated in normal rats. The rats with glioma were grouped to evaluate the role of PD-1 inhibitors combined with FUS-induced immune responses in suppressing glioma when the BBB opens. Flow cytometry was used to examine the changes of immune cell populations of lymphocytes in peripheral blood, tumor tissue and spleen tissue of the rats. A section of rat brain tissue was also used for histological and immunohistochemical analysis. The survival of the rats was then monitored; the tumor progression and changes in blood perfusion of tumor were dynamically observed in vivo using multimodal MRI. RESULTS: FUS combined with microbubbles could enhance the blood perfusion of tumors by increasing the permeability of BBB (p < 0.0001), thus promoting the infiltration of CD4+ T lymphocytes (p < 0.01). Compared with the control group, the combination treatment group had increased in the infiltration number of CD4+(p < 0.05) and CD8+ T (p < 0.05); the tumor volume of the combined treatment group was smaller than that of the control group (p < 0.01) and the survival rate of the rats was prolonged (p < 0.05). CONCLUSIONS: In this study, we demonstrated that the transient opening of the BBB induced by FUS enhanced tumor vascular perfusion and facilitated the delivery of PD-1 inhibitors, ultimately improving the therapeutic efficacy for glioblastoma.

7.
J Hazard Mater ; 479: 135766, 2024 Nov 05.
Article in English | MEDLINE | ID: mdl-39244984

ABSTRACT

Nanoplastics (NPs) pose great challenges to soil-groundwater systems. This study investigated the transport and retention of self-synthesized 0.5-µm polystyrene NPs with different shapes using column experiments. The regular NPs were with spherical shapes, while the irregular NPs were with toroid-like shapes. The toroid-like shapes were the irregular shapes (with low aspect ratio) which have not been studied yet. The explorations were carried out in both 5-25 mM NaNO3 and 1-10 mM Ca(NO3)2 solutions. Both breakthrough curves (BTCs) and retained profiles (RPs) were monitored. Our findings uncovered a clear disparity in the transport of irregular and regular NPs, with irregular particles exhibiting lower transport ability compared to the regular ones. For example, the average breakthrough plateaus of the regular and irregular NPs were ∼0.9 and ∼0.5, respectively, in 10 mM NaNO3. In-depth theoretical analysis indicated that the lower XDLVO interaction energy barrier between the irregular NPs and quartz sand was one factor, and the greater margination of irregular NPs on quartz sand, as verified by the numerical simulation, was another factor leading to the decreased transport and increased retention of the irregular NPs. The obtained results highlighted the significance of considering particle shape in future modelling and predicting the fate of NPs in real environmental circumstances.

8.
Anal Sci ; 2024 Sep 11.
Article in English | MEDLINE | ID: mdl-39259471

ABSTRACT

To develop a clean-up material suitable for high-fat food matrices for detecting mycotoxins in yak ghee, an octadecyl-bonded hectorite (Hectorite@NHCO(CH2)17CH3) was synthesized through multi-step chemical reactions. A modified QuEChERS-HPLC-MS/MS method for detecting ten mycotoxins in sesame oil in yak ghee was established using Hectorite@NHCO(CH2)17CH3 as clean-up agent. It involved extracting mycotoxin contaminants using acidified acetonitrile and employing the Hectorite@NHCO(CH2)17CH3 to remove interfering substances from the extract. The purified samples were then analyzed using HPLC-MS/MS. Within a linear range of 1.0-500 µg/kg, there was a good linear relationship between the quantification ion peak area of the target analytes and the corresponding concentrations (R2 ≥ 0.9991). The limit of detection (LOD) ranged from 0.10 µg/kg to 18.62 µg/kg and the limit of quantitation (LOQ) ranged 0.32-62.07 µg/kg. The recoveries at low, medium and high concentrations (25, 100 and 500 µg/kg) ranged from 72.2% to 113.9%, with relative standard deviations (RSD) between 3.2% and 17.5%. The intra-day and inter-day precision met experimental requirements. The proposed method was characterized by a high accuracy and precision, and it could cater to the current demand for detecting ten mycotoxins in yak ghee.

9.
Cancer Med ; 13(17): e70117, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39248131

ABSTRACT

OBJECTIVE: Previous results about prognostic value of CD4+ T cells in follicular lymphoma (FL) remain controversial. METHODS: Immunohistochemistry was used to examine expression of positive CD4 cells in 103 patients with FL 1-3A. Early failure was described as failing to achieve event-free survival (EFS) at 12 or 24 months. RESULTS: There were 49 (47.6%) male and 54 (52.4%) females, with a median age of 54 years. Compared to patients with <20% of positive CD4 cells, patients with ≥20% of positive CD4 cells exhibited a significant lower risk of early failure (2-year EFS rate: 56.7% vs 73.5%, p = 0.047). When patients were stratified based on positive CD4 cell combined with FLIPI, the median EFS (p = 0.002) and median OS (p = 0.007) were significantly different. CONCLUSIONS: This study demonstrated that higher expression of positive CD4 cells predicts lower risk of early failure in follicular lymphoma, and combination analysis of CD4 and FLIPI could better predict disease relapse and survival outcome.


Subject(s)
CD4-Positive T-Lymphocytes , Lymphoma, Follicular , Humans , Lymphoma, Follicular/mortality , Lymphoma, Follicular/pathology , Lymphoma, Follicular/metabolism , Female , Male , Middle Aged , Aged , Adult , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/metabolism , Prognosis , Aged, 80 and over , Progression-Free Survival
10.
Inorg Chem ; 63(37): 17116-17126, 2024 Sep 16.
Article in English | MEDLINE | ID: mdl-39231020

ABSTRACT

Precisely tuning how and where a reaction occurs in a one-step selective system is important but challenging owing to the similar electronic environments in multiple active sites. In this work, highly selective and effective reaction sites were obtained by generating copper coordination polymers (Cu-CP) of a range of sizes and morphologies, from bulk solid crystals (1) to uniform nanosphere structures (1a), by controlling the amount of surfactant hexadecyl trimethylammonium bromide (CTAB). The results indicated that the morphology and size of the uniform nanosphere structures were affected by the proportion of CTAB; uniform distribution of nanosphere structures was achieved with a premade building carrier when the content of CTAB was 0.005 mmol, generating a well-established platform. Photocatalytic cadmium sulfide (CdS) was then immobilized on the surface of the premade platform unit 1a through an in situ process to generate CdS@1a composites with well-dispersed catalytic CdS active sites. Furthermore, the well-defined CdS@1a composite platform was utilized as photocatalysts to explore the selective one-step depolymerization reaction under blue-light irradiation. Notably, the CdS0.149@1a composite, which featured a unique structure with evenly dispersed, closely spaced catalytic sites, exhibiting remarkable photoelectrochemical behaviors for selective one-step depolymerization of lignin model substances to aromatic monomer phenol and acetophenone framework products. This work demonstrates the use of an inherently morphological process to construct outstanding photocatalysts that could enable a wide range of photocatalytic reactions.

11.
Target Oncol ; 19(5): 723-733, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39231855

ABSTRACT

BACKGROUND: Immune checkpoint blockade with anti-programmed cell death 1 (PD-1) antibodies has demonstrated efficacy in multiple tumor types. Nofazinlimab is a humanized rat antibody targeting PD-1. A first-in-human study of nofazinlimab conducted in Australia found no dose-limiting toxicities (DLTs) and the maximum tolerated dose (MTD) was not reached in the range of 1-10 mg/kg. OBJECTIVE: We evaluated nofazinlimab for multiple advanced malignancies in Chinese patients. PATIENTS AND METHODS: This was a phase 1a/1b, open-label, multicenter, dose-escalation/expansion trial. In phase 1a, patients received an abbreviated dose escalation of nofazinlimab at 60 mg and 200 mg every 3 weeks (Q3W) to determine DLTs and the recommended phase 2 dose (RP2D). In phase 1b, patients received the RP2D (monotherapy/combination) in six arms by tumor type; DLTs were evaluated for nofazinlimab plus lenvatinib in the unresectable hepatocellular carcinoma (uHCC) arm. Safety (continuously monitored in patients who received nofazinlimab) and efficacy (patients with measurable baseline disease) were assessed. RESULTS: Overall, 107 patients were eligible and received nofazinlimab. In phase 1a, no DLTs were observed; the RP2D was 200mg Q3W. In phase 1b, no DLTs were observed with nofazinlimab plus lenvatinib. The safety profile was consistent with that observed in the first-in-human study (NCT03475251). In phase 1b, 21/88 (23.9%) patients achieved confirmed objective responses, 26 (29.5%) had stable disease, and 9/20 (45.0%) patients with uHCC achieved confirmed objective responses to nofazinlimab plus lenvatinib. CONCLUSIONS: Nofazinlimab was well tolerated in Chinese patients. Preliminary efficacy was encouraging, particularly for nofazinlimab plus lenvatinib in uHCC, which is being studied in an ongoing phase 3 trial. CLINICAL TRIAL REGISTRATION: NCT03809767; registered 18 January 2019.


Subject(s)
Lymphoma , Neoplasms , Humans , Male , Female , Middle Aged , Lymphoma/drug therapy , Neoplasms/drug therapy , Aged , Adult , China , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/pharmacology , Maximum Tolerated Dose , East Asian People
12.
Mol Neurobiol ; 2024 Sep 07.
Article in English | MEDLINE | ID: mdl-39243325

ABSTRACT

Pathogenic variants of mitochondrial DNA (mtDNA) are associated with a large number of heterogeneous diseases involving multiple systems with which patients may present with a wide range of clinical phenotypes. Clinical data of the proband and his family members were gathered in a retrospective study. Whole-exome sequencing and full-length sequencing of the mitochondrial genome that was performed on peripheral blood, urine, and oral mucosa cells were applied for genetic analysis. In this study, we describe a 2-year-old Chinese boy with global developmental delay, Charcot-Marie-Tooth (CMT) disease, progressive myoclonic epilepsy, paroxysmal arrhythmia, and brain atrophy with elevated blood lactate levels. The clinical manifestations of the patient were improved after metabolic therapy, but the development regressed after infection. The molecular finding of whole-exome sequencing is unremarkable, but the mtDNA genome sequencing of the proband and his monther revealed a de novo novel heteroplasmic variant, m.1636A > G, located next to the highly conserved anticodon loop of tRNA Val (MT-TV) gene. Moreover, the higher levels of mutational load in urinary epithelial cells (19.05%) and oral mucosa cells (20.8%) were detected than that in blood (17.4%). Combined with the phenotypic and molecular genetics analysis of this family, this novel variation was currently considered to be a likely pathogenic variant. Our results added evidence that the de novo m.1636A > G variation in the highly conserved sequence of MT-TV appears to suggest a childhood-onset mitochondrial phenotype of a 2-year-old patient, thus broaden the genotypic interpretation of mitochondrial DNA-related disease.

13.
Haematologica ; 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-39234866

ABSTRACT

Patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) have a poor prognosis. Loncastuximab tesirine (Lonca), an antibody conjugate targeting CD19, has demonstrated significant clinical benefit in R/R DLBCL in a global phase 2 LOTIS-2 study. In the China bridging pivotal phase 2 OL-ADCT-402-001 study, eligible patients aged ≥18 years with R/R DLBCL who had failed ≥ 2 lines of systemic therapies were enrolled and treated with Lonca every 3 week with 150 µg/kg for 2 cycles; then 75 µg/kg for subsequent cycles (up to 1 year). The primary endpoint was overall response rate (ORR) assessed by independent review committee. Primary analyses for efficacy and safety were performed on the patients who received at least one treatment and had at least 6 months of follow-up following an initial documented response. As of data-cutoff, 64 patients received Lonca (median: 4.0 cycles [range: 1 to 17]). The median number of prior lines of therapies was 3.0 (range: 2 to 12). The ORR was 51.6% (95% CI: 38.7% to 64.2%), and the complete response rate was 23.4%. Hematological events accounted for the majority of the most common (≥15%) Grade ≥3 treatment-emergent adverse events (TEAEs), in which increased gamma glutamyltransferase (25.0%), and hypokalaemia (18.8%) also were reported. Serious TEAEs were reported in 35 of 64 patients with 4 fatal TEAEs. In conclusion, Lonca monotherapy demonstrated clinically meaningful efficacy and was well-tolerated in heavily pretreated Chinese patients with R/R DLBCL, which was consistent with the results of the LOTIS-2 study in Caucasian patients.

14.
Med Int (Lond) ; 4(6): 67, 2024.
Article in English | MEDLINE | ID: mdl-39268247

ABSTRACT

As a notorious bacterial pathogen, Staphylococcus aureus (S. aureus) can readily induce infections in the community and hospital, causing significant morbidity and mortality. With the extensive rise of multiple resistance, conventional antibiotic therapy has rapidly become ineffective for related infections. Resveratrol is a naturally occurring polyphenolic substance that has been demonstrated to have effective antimicrobial activity against S. aureus. Resveratrol at sub-inhibitory doses can suppress the expression of virulence factors, contributing to attenuated biofilm formation, interference with quorum sensing and the inhibition of the production of toxins. As a promising efflux pump inhibitor, resveratrol enhances antibiotic susceptibility to a certain extent. In conjunction with conventional antibiotics, resveratrol displays unique synergistic effects with norfloxacin and aminoglycoside on S. aureus, yet antagonizes the lethal effects of daptomycin, oxacillin, moxifloxacin and levofloxacin. Nevertheless, given the low oral bioavailability of resveratrol, advanced formulations need to be developed to delay the rapid metabolism conversion to low or inactive conjugates. The present review discusses the antibacterial properties of resveratrol against S. aureus, in an aim to provide in-depth insight for researchers to address the challenges of antimicrobial resistance.

15.
Biomed Rep ; 21(5): 161, 2024 Nov.
Article in English | MEDLINE | ID: mdl-39268408

ABSTRACT

Nanoparticles (NPs) are one of the promising strategies to deal with bacterial infections. As the main subset of NPs, metal and metal oxide NPs show destructive power against bacteria by releasing metal ions, direct contact of cell membranes and antibiotic delivery. Recently, a number of researchers have focused on the antibacterial activity of zinc oxide nanoparticles (ZnO NPs) against Staphylococcus aureus (S. aureus). Currently, there is a lack of a comprehensive review on ZnO NPs against S. aureus. Therefore, in this review, the antibacterial activity against S. aureus of ZnO NPs made by various synthetic methods was summarized, particularly the green synthetic ZnO NPs. The synergistic antibacterial effect against S. aureus of ZnO NPs with antibiotics was also summarized. Furthermore, the present review also emphasized the enhanced activities against S. aureus of ZnO nanocomposites, nano-hybrids and functional ZnO NPs.

16.
Inorg Chem ; 2024 Sep 13.
Article in English | MEDLINE | ID: mdl-39270127

ABSTRACT

In order to facilitate the practical application of circularly polarized luminescence (CPL) active molecules, the CPL brightness (BCPL) must be optimized. We have applied a binary modular strategy to synthesize two chiral organo-Tb3+ complexes, [Tb(Coum)3(1R,2R-Ph-PyBox)] (2) and [Tb(Coum)3(1S,2S-Ph-PyBox)] (5), combining 3-acetyl-4-hydroxy-coumarin (Coum) and enantiopure 2,6-bis(4-phenyl-2-oxazolin-2-yl) pyridine (1R,2R/1S,2S-Ph-PyBox). The photophysical properties of these novel complexes have been fully characterized. The combined point-chiral induction capability of chiral bis(oxazoline) derivatives and the outstanding photophysical properties of the coumarin-derived ligand have resulted in an intense excited-state chiroptical activity (|glum| = 0.097-0.103) for both Tb3+ enantiomers, with a bright Tb3+-centered high-purity green emission (ΦPL = 74%) and enhanced antenna-centered absorption behavior (ε320 nm = 47820-47940 M-1 cm-1). A superior BCPL (1132.7-1205.8 M-1 cm-1 at 5D4 → 7F5) has been established for complexes 2 and 5. The strategy adopted in this work provides a new route to chiroptical organo-Tb3+ luminophores with outstanding comprehensive performance.

17.
Acta Pharmacol Sin ; 2024 Sep 02.
Article in English | MEDLINE | ID: mdl-39223367

ABSTRACT

PANoptosis is an emerging form of regulated cell death (RCD) characterized by simultaneous activation of pyroptotic, apoptotic, and necroptotic signaling that not only participates in pathologies of inflammatory diseases but also has a critical role against pathogenic infections. Targeting PANoptosis represents a promising therapeutic strategy for related inflammatory diseases, but identification of inhibitors for PANoptosis remains an unmet demand. Baicalin () is an active flavonoid isolated from Scutellaria baicalensis Georgi (Huangqin), a traditional Chinese medicinal herb used for heat-clearing and detoxifying. Numerous studies suggest that baicalin possesses inhibitory activities on various forms of RCD including apoptosis/secondary necrosis, pyroptosis, and necroptosis, thereby mitigating inflammatory responses. In this study we investigated the effects of baicalin on PANoptosis in macrophage cellular models. Primary macrophages (BMDMs) or J774A.1 macrophage cells were treated with 5Z-7-oxozeaenol (OXO, an inhibitor for TAK1) in combination with TNF-α or LPS. We showed that OXO plus TNF-α or LPS induced robust lytic cell death, which was dose-dependently inhibited by baicalin (50-200 µM). We demonstrated that PANoptosis induction was accompanied by overt mitochondrial injury, mitochondrial DNA (mtDNA) release and Z-DNA formation. Z-DNA was formed from cytosolic oxidized mtDNA. Both oxidized mtDNA and mitochondrial Z-DNA puncta were co-localized with the PANoptosome (including ZBP1, RIPK3, ASC, and caspase-8), a platform for mediating PANoptosis. Intriguingly, baicalin not only prevented mitochondrial injury but also blocked mtDNA release, Z-DNA formation and PANoptosome assembly. Knockdown of ZBP1 markedly decreased PANoptotic cell death. In a mouse model of hemophagocytic lymphohistiocytosis (HLH), administration of baicalin (200 mg/kg, i.g., for 4 times) significantly mitigated lung and liver injury and reduced levels of serum TNF-α and IFN-γ, concomitant with decreased levels of PANoptosis hallmarks in these organs. Baicalin also abrogated the hallmarks of PANoptosis in liver-resident macrophages (Kupffer cells) in HLH mice. Collectively, our results demonstrate that baicalin inhibits PANoptosis in macrophages by blocking mitochondrial Z-DNA formation and ZBP1-PANoptosome assembly, thus conferring protection against inflammatory diseases. PANoptosis is a form of regulated cell death displaying simultaneous activation of pyroptotic, apoptotic, and necroptotic signaling. This study shows that induction of PANoptosis is linked to mitochondrial dysfunction and mitochondrial Z-DNA formation. Baicalin inhibits PANoptosis in macrophages in vitro via blocking mitochondrial dysfunction and the mitochondrial Z-DNA formation and thereby impeding the assembly of ZBP1-associated PANoptosome. In a mouse model of hemophagocytic lymphohistiocytosis (HLH), baicalin inhibits the activation of PANoptotic signaling in liver-resident macrophages (Kupffer cells) in vivo, thus mitigating systemic inflammation and multiple organ injury in mice.

18.
Chemosphere ; 364: 143104, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39159764

ABSTRACT

Arsenic contamination of water is a global environmental concern, and membrane technology combined with nanotechnology contributes to more efficient removal of arsenic. In this study, Fe-Mn oxide (FM), Polydopamine (PDA), and PDA-modified FM (PFM) were incorporated into polysulfone (PSF) to prepare adsorption membranes (PFMP) for arsenic removal. The prepared nanoparticles and membranes were characterized using TEM, SEM, FTIR, TGA, contact angle, and pure water flux. The introduction of particles enhanced the hydrophilicity of the membranes and significantly enhanced the pure water flux of the membranes. Adsorption experiments indicated that the PFMP membrane exhibited the best arsenic removal performance, with maximum adsorption capacities for As(III) and As(V) were 11.57 mg/g and 12.39 mg/g, respectively. The Langmuir model fitted the adsorption isotherms well, and the kinetics followed the pseudo-second-order model. The filtration experiment revealed that the PFMP membrane was capable of reducing As(III) solution (915 L/m2) and As(V) solution (1075 L/m2) from a concentration of 100 µg/L to the safe limit of As (<10 µg/L). The As-loaded membrane was regenerated using NaOH solution (pH = 11), and the filtration experiment was repeated. FTIR and XPS demonstrated that the mechanism of the reaction between the membrane and arsenic was ligand exchange, where the arsenic ions were bonded to the oxygen ions to form Mn-O-As and Fe-O-As.


Subject(s)
Arsenates , Indoles , Oxides , Polymers , Sulfones , Water Pollutants, Chemical , Water Purification , Indoles/chemistry , Polymers/chemistry , Adsorption , Water Pollutants, Chemical/chemistry , Arsenates/chemistry , Water Purification/methods , Oxides/chemistry , Sulfones/chemistry , Membranes, Artificial , Nanoparticles/chemistry , Kinetics , Ferric Compounds/chemistry , Manganese Compounds/chemistry , Arsenic/chemistry , Arsenic/analysis
19.
Sci Total Environ ; 950: 175357, 2024 Nov 10.
Article in English | MEDLINE | ID: mdl-39127203

ABSTRACT

Klebsiella pneumoniae (Kp) is a human symbiotic opportunistic pathogen capable of causing severe hospital-based infections and community-acquired infections. The problem of antimicrobial resistance (AMR) has become increasing serious over time, posing a major threat to socio-economic and human development. In this study, we explored the global trend of AMR in 1786 strains of Kp isolated between 1982 and 2023. The number of antibiotic resistance genes (ARGs) in Kp increased significantly from 24.29 ± 5.44 to 32.42 ± 8.52 over time. Mobile genetic elements (MGEs) were responsible for the ARGs horizontal transfer of Kp strains. The results of structural equation modeling (SEM) indicated a strong association between the human development index and the increase of antibiotic consumption, which indirectly affected the occurrence and development of antibiotic resistance in Kp. The results of Generalized Linear Models (GLM) indicated that the influence of environmental factors such as temperature on the development of Kp resistance could not be ignored. Overall, this study monitored the longitudinal trend of antimicrobial resistance in Kp, explored the factors influencing antibiotic resistance, and provided insights for mitigating the threat of antimicrobial resistance.


Subject(s)
Anti-Bacterial Agents , Drug Resistance, Bacterial , Klebsiella pneumoniae , Klebsiella pneumoniae/drug effects , Klebsiella pneumoniae/genetics , Anti-Bacterial Agents/pharmacology , Drug Resistance, Bacterial/genetics , Humans , Klebsiella Infections/drug therapy , Klebsiella Infections/microbiology
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