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1.
Insect Mol Biol ; 2024 Jul 06.
Article in English | MEDLINE | ID: mdl-38970387

ABSTRACT

Insect reproductive capacity can affect effective pest control and infertility studies and has become an important focus in recent molecular genetic research. Nucleosome assembly protein (Nap) is highly conserved across multiple species and is involved in forming the sperm nucleus in many species. We used clustered regularly interspaced palindromic repeats/Cas9 technology to knockout BmNap in Bombyx mori and observed that the mutations caused female infertility, whereas male fertility was not affected. BmNap mutants grew and mated normally; however, female mutants laid smaller eggs that could not be fertilised and did not hatch. In addition, female sterility produced by the mutation could be inherited stably via male mutants; therefore, Nap could be used as a potential target for lepidopteran pest control through population regulation. In the current study, we elucidated a new function of BmNap, increased the understanding of the oogenesis regulation network in Lepidoptera and promoted the development of insect sterility technologies.

2.
Environ Pollut ; 358: 124487, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38960121

ABSTRACT

Low activation performance is a critical issue limiting the practical application of low-cost biochar in the advanced oxidation. Given the high potential of transition metals in the persulfate activation process and abundant oxygen-containing groups of hydrochar, hydrochar derived from cobalt (Co)-modified iron (Fe)-enriched sludge was synthesized and its performance and activation mechanism for the degradation of triclosan were investigated. Co modification significantly altered the morphology of hydrochar, and the increased Co-Fe mass ratios transformed hydrochar from granular to rose-shaped lamellar and then to helical sheet structures. Specific surface area, defect degree, and oxygen-containing groups of hydrochar increased with increasing cobalt-iron mass ratios. The highest removal of triclosan was up to 98% in the hydrochar/peroxymonosulfate (PMS) system under a wide range of pHs (3-10) and still remained higher than 90% after four cycles. Both Radical (mainly hydroxyl radical) and nonradical pathways (singlet oxygen and electron transfer) were evidenced to play roles in the triclosan removal. Fe3+ promoted the regeneration of Co2+ and realized the efficient circulation of Co3+/Co2+. A ternary system consisting of electron donor (triclosan)-electron mediator (hydrochar)-electron acceptor (PMS) provided channels for electron transfer. No measurable Co and Fe were released during the reaction, and the toxicity of degradation intermediates was lower than that of triclosan. Beside triclosan, rhodamine B, bisphenol A, sulfamethoxazole, and phenol were also almost degraded completely in this oxidation system. This study provides a promising way for the enhancement of catalytic activity of carbonaceous material.

3.
J Org Chem ; 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38952027

ABSTRACT

A visible-light-induced radical-radical cross-coupling reaction between 1,3,4-oxadiazoles and hydroxamic acid derivatives has been realized under base- and metal-free conditions. The protocol was characterized by broad substrate scope, excellent functional group tolerance, and simple operation procedures. By using this protocol, a variety of biologically important 5-aryl-1,3,4-oxadiazole-2-methylamines were obtained in good yields with excellent chemoselectivity.

4.
Front Vet Sci ; 11: 1413420, 2024.
Article in English | MEDLINE | ID: mdl-38919159

ABSTRACT

Canine distemper virus (CDV) is a highly contagious and potentially lethal virus that affects dogs and other members of the Canidae family, including wolves, foxes, and coyotes. Here, we present a fluorescent lateral flow immunoassay (FLFA) platform for the detection of CDV, which utilizes fluorescent microspheres - fusion protein monoclonal antibody (mAb)-labeled monoclonal antibody. The assay detected CDV within 5 min, with a detection limit threshold of 3 × 102 TCID50/mL. Notably, the assay demonstrated no cross-reactivity with canine parvovirus, canine coronavirus, canine adenovirus, feline calicivirus, feline herpesvirus, or feline parvovirus. Field and clinical applicability of the assay was evaluated using 63 field samples, including 30 canine fecal samples, 18 swab samples, and 15 blood samples. The coincidence rate between the detection results of clinical samples obtained through FLFA and reverse transcription polymerase chain reaction (RT-PCR) was 96.83%. Thus, this assay offers a significant advancement for the rapid diagnosis of CDV at the point of care.

5.
J Physiol ; 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38837412

ABSTRACT

In mammals, odour information within the olfactory bulb (OB) is processed by complex neural circuits before being ultimately represented in the action potential activity of mitral/tufted cells (M/Ts). Cholecystokinin-expressing (CCK+) superficial tufted cells (sTCs) are a subset of tufted cells that potentially contribute to olfactory processing in the OB by orchestrating M/T activity. However, the exact role of CCK+ sTCs in modulating odour processing and olfactory function in vivo is largely unknown. Here, we demonstrate that manipulating CCK+ sTCs can generate perception and induce place avoidance. Optogenetic activation/inactivation of CCK+ sTCs exerted strong but differing effects on spontaneous and odour-evoked M/T firing. Furthermore, inactivation of CCK+ sTCs disrupted M/T odour encoding and impaired olfactory detection and odour discrimination. These results establish the role of CCK+ sTCs in odour representation and olfactory behaviours. KEY POINTS: Mice could perceive the activity of CCK+ sTCs and show place avoidance to CCK+ sTC inactivation. Optical activation of CCK+ sTCs increased the percentage of cells with odour response but reduced the odour-evoked response in M/Ts in awake mice. Optical inactivation of CCK+ sTCs greatly decreased spontaneous firing and odour-evoked response in M/Ts. Inactivation of CCK+ sTCs impairs the odour decoding performance of M/Ts and disrupts odour detection and discrimination behaviours in mice. These results indicate that CCK+ sTCs participate in modulating the odour representation and maintaining normal olfactory-related behaviours.

6.
bioRxiv ; 2024 Jun 02.
Article in English | MEDLINE | ID: mdl-38854050

ABSTRACT

Protein arginylation is an essential posttranslational modification (PTM) catalyzed by arginyl-tRNA-protein transferase 1 (ATE1) in mammalian systems. Arginylation features a post-translational conjugation of an arginyl to a protein, making it extremely challenging to differentiate from translational arginine residues with the same mass in a protein sequence. Here we present a general activity-based arginylation profiling (ABAP) platform for the unbiased discovery of arginylation substrates and their precise modification sites. This method integrates isotopic arginine labeling into an ATE1 assay utilizing biological lysates (ex vivo) rather than live cells, thus eliminating translational bias derived from the ribosomal activity and enabling bona fide arginylation identification using isotopic features. ABAP has been successfully applied to an array of peptide, protein, cell, patient, and animal tissue samples using 20 µg sample input, with 229 unique arginylation sites revealed from human proteomes. Representative sites were validated and followed up for their biological functions. The developed platform is globally applicable to the aforementioned sample types and therefore paves the way for functional studies of this difficult-to-characterize protein modification.

7.
Front Public Health ; 12: 1387330, 2024.
Article in English | MEDLINE | ID: mdl-38841686

ABSTRACT

Background: Owing to the long penetration depth of gamma (γ)-rays, individuals working in ionizing radiation environments are chronically exposed to low-dose γ-radiation, resulting in cognitive changes. Dose rate significantly affects radiation-induced biological effects; however, its role in chronic low-dose γ-irradiation-induced cognitive impairment remains unclear. We aimed to investigate whether chronic low-dose γ-irradiation at low-dose-rate (LDR) could induce cognitive impairment and to compare the cognitive alteration caused by chronic low-dose γ-irradiation at LDR and high-dose-rate (HDR). Methods: The rats were exposed to γ-irradiation at a LDR of 6 mGy/h and a HDR of 20 mGy/h for 30 days (5 h/day). Functional imaging was performed to assess the brain inflammation and blood-brain barrier (BBB) destruction of rats. Histological and immunofluorescence analyses were used to reveal the neuron damage and the activation of microglia and astrocytes in the hippocampus. RNA sequencing was conducted to investigate changes in gene expression in hippocampus. Results: The rats in the LDR group exhibited more persistent cognitive impairment than those in the HDR group. Furthermore, irradiated rats showed brain inflammation and a compromised BBB. Histologically, the number of hippocampal neurons were comparable in the LDR group but were markedly decreased in the HDR. Additionally, activated M1-like microglia and A1-like astrocytes were observed in the hippocampus of rats in the LDR group; however, only M1-like microglia were activated in the HDR group. Mechanistically, the PI3K-Akt signaling pathway contributed to the different cognitive function change between the LDR group and HDR group. Conclusion: Compared with chronic low-dose γ-irradiation at HDR, LDR induced more severe cognitive impairment which might involve PI3K/Akt signaling pathway.


Subject(s)
Cognitive Dysfunction , Gamma Rays , Animals , Gamma Rays/adverse effects , Rats , Cognitive Dysfunction/etiology , Male , Hippocampus/radiation effects , Rats, Sprague-Dawley , Dose-Response Relationship, Radiation , Blood-Brain Barrier/radiation effects
8.
J Environ Sci (China) ; 145: 128-138, 2024 Nov.
Article in English | MEDLINE | ID: mdl-38844313

ABSTRACT

Zeolites are a promising support for Pd catalysts in lean methane (CH4) combustion. Herein, three types of zeolites (H-MOR, H-ZSM-5 and H-Y) were selected to estimate their structural effects and deactivation mechanisms in CH4 combustion. We show that variations in zeolite structure and surface acidity led to distinct changes in Pd states. Pd/H-MOR with external high-dispersing Pd nanoparticles exhibited the best apparent activity, with activation energy (Ea) at 73 kJ/mol, while Pd/H-ZSM-5 displayed the highest turnover frequency (TOF) at 19.6 × 10-3 sec-1, presumably owing to its large particles with more step sites providing active sites in one particle for CH4 activation. Pd/H-Y with dispersed PdO within pore channels and/or Pd2+ ions on ion-exchange sites yielded the lowest apparent activity and TOF. Furthermore, Pd/H-MOR and Pd/H-ZSM-5 were both stable under a dry condition, but introducing 3 vol.% H2O caused the CH4 conversion rate on Pd/H-MOR drop from 100% to 63% and that on Pd/H-ZSM-5 decreased remarkably from 82% to 36%. The former was shown to originate from zeolite structural dealumination, and the latter principally owed to Pd aggregation and the loss of active PdO.


Subject(s)
Methane , Palladium , Zeolites , Zeolites/chemistry , Methane/chemistry , Catalysis , Palladium/chemistry , Models, Chemical
9.
Oncol Lett ; 28(2): 347, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38872858

ABSTRACT

The use of tyrosine kinase inhibitors combined with transarterial chemoembolization (TACE) is considered the standard therapy for patients with unresectable hepatocellular carcinoma (uHCC). However, information regarding the efficacy of lenvatinib or sorafenib in combination with TACE for patients with uHCC is limited. The present study involved a systematic search for randomized controlled trials on the PubMed, Embase, Web of Science and the Cochrane Library online databases to compare the use of TACE combined with either lenvatinib or sorafenib, and monotherapy using either lenvatinib or sorafenib for patients with uHCC. The network meta-analysis of the present study included eight randomized controlled trials involving 2,929 patients. The random-effects model was used, and hazard ratios and risk ratios with 95% CIs were calculated. Lenvatinib in combination with TACE provided the maximal overall survival (97.92%), progression-free survival (87.8%), objective response (96.68%) and disease control (96.27%) rates. The results of the present study indicated that, in the treatment of patients with uHCC, lenvatinib in combination with TACE showed a significantly improved efficacy when compared with sorafenib and TACE. Therefore, in the future, combination therapy of lenvatinib with TACE could be potentially prioritized over sorafenib with TACE for the treatment of patients with uHCC.

10.
Microbiol Spectr ; : e0309523, 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38899904

ABSTRACT

Antibiotics are widely used to treat bacterial infection and reduce the mortality rate, while antibiotic overuse can cause gut microbiota dysbiosis. The impact of antibiotics on gut microbiota is not fully understood. In our study, four commonly used antibiotics (ceftazidime, cefoperazone-sulbactam, imipenem-cilastatin, and moxifloxacin) were given subcutaneously to mice, and their impacts on the gut microbiota composition and serum cytokine levels were evaluated through 16S rRNA analysis and a multiplex immunoassay. Antibiotic treatment markedly reduced gut microbiota diversity and changed gut microbiota composition. Antibiotic treatment significantly increased and decreased the abundance of Firmicutes and Bacteroidota, respectively. The antibiotic treatments increased the abundance of opportunistic pathogens such as Enterococcus and decreased that of Lachnospiraceae and Muribaculaceae. For moxifloxacin, the significantly high abundance of Enterococcus and Klebsiella was observed after 14 and 21 days of treatment. However, a relatively low abundance of opportunistic pathogens was found after 14 days of imipenem-cilastatin treatment. Additionally, the serum levels of various pro-inflammatory cytokines, such as IL-1ß, IL-12 (p70), and IL-17, significantly increased after 21 days of antibiotic treatments. Overall, these results provide a guide for rational use of antibiotics in clinical settings: short-term use of moxifloxacin is recommended with regard to gut microbiota health, and the 14-day use of imipenem-cilastatin may have a less severe impact than other antibiotics.IMPORTANCEAntibiotic treatments are directly associated with changes in gut microbiota and are effective against both pathogens and beneficial bacteria. Gut microbiota dysbiosis induced by antibiotic treatment could increase the risk of some diseases. Therefore, an adequate understanding of gut microbiota changes after antibiotic use is crucial. In this study, we investigated the effects of continuous treatment with antibiotics on gut microbiota, serum cytokines, and intestinal inflammatory response. Our results suggest that short-term use of moxifloxacin is recommended, and the 14-day use of imipenem-cilastatin may have a less severe effect on gut microbiota health than cefoperazone-sulbactam. These results provide useful guidance on the rational use of antibiotics with regard to gut microbiota health.

11.
Curr Pharm Des ; 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38910414

ABSTRACT

BACKGROUND: Salivary Adenoid Cystic Carcinoma (ACC) is characterized by a highly invasive and slow-growing pattern, and its etiology remains unidentified. Triptonide (TN) has demonstrated efficacy as a pharmacotherapeutic agent against ACC. Nonetheless, the specific targets and mechanism of molecular action underlying the effectiveness of TN in treating ACC have not been elucidated. OBJECTIVES: By integrating network pharmacology with in-laboratory experiments, this research delves into the prospective targets and molecular mechanisms associated with the application of TN in treating ACC. METHODS: Initially, pertinent targets associated with TN against ACC were acquired from public databases. Subsequently, a combination of network pharmacology and bioinformatics analysis was utilized to screen the top 10 hub targets and key signal pathways of TN-treating ACC. Finally, in vitro experiments involving various molecular assays were conducted to evaluate the biological phenotypes of cells following TN treatment, encompassing assessments of apoptosis levels, plate migration, and other parameters, thereby validating pivotal genes and pathways. RESULTS: A total of 23 pertinent targets for TN in relation to ACC were identified, with the top 10 hub genes being MAPK8, PTGS2, RELA, MAPK14, NR3C1, HDAC1, PPARG, NFKBIA, AR, and PGR. There was a significant correlation between the TNF signaling pathway and the treatment of ACC with TN. In vitro experiments demonstrated that TN treatment elevated RELA phosphorylation while concurrently reducing MAPK14 phosphorylation and inducing G2/M arrest. TN exhibited the ability to enhance the apoptosis rate through increased caspase-3 activity, elevated levels of Reactive Oxygen Species (ROS), mitochondrial dysfunction, and inhibition of cell migration. CONCLUSION: There is a potential therapeutic role for TN in the treatment of ACC through the activation of the TNF signaling pathway. Among the identified candidates, MAPK8, HDAC1, PTGS2, RELA, NR3C1, PPARG, NFKBIA, AR, and PGR emerge as the most pertinent therapeutic targets for TN in the context of ACC treatment.

12.
J Hazard Mater ; 474: 134573, 2024 Aug 05.
Article in English | MEDLINE | ID: mdl-38824779

ABSTRACT

It has been demonstrated that microplastics (MPs) may be inadvertently ingested by aquatic animals, causing harm to their physiological functions and potentially entering the food chain, thereby posing risks to human food safety. To achieve an environmentally friendly and efficient reduction of MPs in freshwater environments, this experiment investigates the depuration effect of C. demersum on MPs using three common aquatic animals: Macrobrachium nipponense, Corbicula fluminea, and Bellamya aeruginosa as research subjects. The amounts of MPs, digestive enzyme activity, oxidative stress index, and energy metabolism enzyme activity in the digestive and non-digestive systems of three aquatic animals were measured on exposure days 1, 3, and 7 and on depuration days 1 and 3. The results indicated that the depuration effect of C. demersum and the species interaction were significant for the whole individual. Concerning digestive tissue, C. demersum was the most effective in purifying B. aeruginosa. When subjected to short-term exposure to MPs, C. demersum displayed a superior depuration effect. Among non-digestive tissues, C. demersum exhibited the earliest purifying effect on C. fluminea. Additionally, C. demersum alleviated physiological responses caused by MPs. In conclusion, this study underscores C. demersum as a promising new method for removing MPs from aquatic organisms.


Subject(s)
Corbicula , Microplastics , Water Pollutants, Chemical , Animals , Microplastics/toxicity , Water Pollutants, Chemical/toxicity , Water Pollutants, Chemical/metabolism , Corbicula/metabolism , Corbicula/drug effects , Palaemonidae/metabolism , Stress, Physiological , Oxidative Stress/drug effects , Chlorophyceae/metabolism
13.
Microorganisms ; 12(6)2024 May 30.
Article in English | MEDLINE | ID: mdl-38930499

ABSTRACT

Soil desertification is an important challenge in global soil management, and effectively and stably restoring soil function is an urgent problem. Using synthetic microbial communities (SynComs) is a burgeoning microbial strategy aimed at enhancing soil nutrients through functional synergies among diverse microorganisms; nevertheless, their effectiveness in restoring desertified soils remains unknown. In this study, we conducted a two-year field experiment using a SynCom constructed by in situ probiotic bacteria and set up control, chemical fertilizer, and combined SynCom-chemical fertilizer (combined fertilizer) treatments to investigate the linkage between microbial communities and soil multifunctionality in the soil surface layer (0-10 cm). Both the bacterial and fungal communities differed the most under the combined fertilizer treatment compared to the control. The bacterial communities differed more under treatments of the SynCom than the chemical fertilizer, while the fungal communities differed more under the chemical fertilizer treatment than the SynCom treatment. Regarding soil function, the SynCom strengthened the correlation between enzyme activities and both bacterial communities and functional properties. pH and available potassium were the main influencing factors under the chemical fertilizer and combined fertilizer treatments. The beta-diversity of the bacterial communities was significantly correlated with soil multifunctionality. Random forest analyses showed that the SynCom significantly enhanced the bacterial communities, driving soil multifunctionality, and that some potential microbial taxa drove multiple nutrient cycles simultaneously. In summary, the SynCom effectively increased the abundance of most carbon, nitrogen, and phosphorus functional genes as well as soil enzyme activities. The bacterial community composition contributed significantly to soil multifunctionality. Hence, the development of novel microbial agents holds significant potential for improving soil functionality and managing desertification.

14.
J Cancer Res Clin Oncol ; 150(5): 285, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38814494

ABSTRACT

INTRODUCTION: For HR-positive/HER2-negative patients who can undergo breast-conserving surgery (BCS) but have a tumor size of 2-5 cm or 1-3 lymph node metastases, neoadjuvant chemotherapy (NAC) is still controversial. METHODS: Patients with T2N0-1M0 HR-positive/HER2-negative BC who underwent BCS between 2010 and 2017 were selected from the SEER database. Propensity score matching (PSM) was used to minimize the influence of confounding factors. The overall survival (OS) and breast cancer-specific survival (BCSS) of patients were estimated by Kaplan‒Meier curves and Cox proportional hazard models. Independent prognostic factors were included to construct a nomogram prediction model. RESULTS: A total of 6475 BC patients were enrolled, of whom 553 received NAC and 5922 received adjuvant chemotherapy (AC). In the T2N0-1M0 population and T2N1M0 subgroup, AC patients before PSM had better OS and BCSS than NAC patients. After PSM, there was no significant difference in OS or BCSS between the two groups. However, in the T2N0M0 subgroup, there was no difference in survival between the AC and NAC groups before and after PSM. Stratified analysis revealed that for complete response (CR) patients, survival was roughly equivalent between the NAC and AC groups. However, the survival of no response (NR) and partial response (PR) patients was significantly worse than that of AC patients. Cox analysis revealed that radiotherapy after BCS was an independent protective factor for OS. NAC is an independent risk factor for NR and PR patients. The nomogram has good prediction efficiency. CONCLUSION: NAC before BCS is not necessary for T2N0-1M0 HR-positive/HER2-negative BC patients.


Subject(s)
Breast Neoplasms , Mastectomy, Segmental , Neoadjuvant Therapy , Receptor, ErbB-2 , Humans , Female , Breast Neoplasms/pathology , Breast Neoplasms/drug therapy , Breast Neoplasms/surgery , Breast Neoplasms/metabolism , Breast Neoplasms/mortality , Breast Neoplasms/therapy , Neoadjuvant Therapy/methods , Middle Aged , Receptor, ErbB-2/metabolism , Chemotherapy, Adjuvant/methods , Adult , Aged , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , Retrospective Studies , Neoplasm Staging , Prognosis , SEER Program
15.
Biomater Sci ; 12(12): 3175-3192, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38742916

ABSTRACT

The tumor immunosuppressive microenvironment (TIME) and uncontrollable release of antigens can lower the efficacy of nanovaccine-based immunotherapy (NBI). Therefore, it is necessary to develop a new strategy for TIME reshaping and controllable release of antigens to improve the NBI efficacy. Herein, an acidity-responsive Schiff base-conjugated polyphenol-coordinated nanovaccine was constructed for the first time to realize bidirectional TIME reshaping and controllable release of antigens for activating T cells. In particular, an acidity-responsive tannic acid-ovalbumin (TA-OVA) nanoconjugate was prepared via a Schiff base reaction. FeIII was coordinated with TA-OVA to produce a FeIII-TA-OVA nanosystem, and 1-methyltryptophan (1-MT) as an indoleamine 2,3-dioxygenase inhibitor was loaded to form a polyphenol-coordinated nanovaccine. The coordination between FeIII and TA could cause photothermal ablation of primary tumors, and the acidity-triggered Schiff base dissociation of TA-OVA could controllably release OVA to realize lysosome escape, initiating the body's immune response. More importantly, oxidative stress generated by a tumor-specific Fenton reaction of Fe ions could promote the polarization of tumor-associated macrophages from the M2 to M1 phenotype, resulting in the upregulation of cytotoxic T cells and helper T cells. Meanwhile, 1-MT could downregulate immunosuppressive regulatory T cells. Overall, such skillful combination of bidirectional TIME reshaping and controllable antigen release into one coordination nanosystem could effectively enhance the NBI efficacy of tumors.


Subject(s)
Immunotherapy , Ovalbumin , Polyphenols , Schiff Bases , Tannins , Tumor Microenvironment , Animals , Tumor Microenvironment/drug effects , Ovalbumin/immunology , Ovalbumin/chemistry , Ovalbumin/administration & dosage , Polyphenols/chemistry , Polyphenols/pharmacology , Mice , Tannins/chemistry , Tannins/pharmacology , Schiff Bases/chemistry , Hydrogen-Ion Concentration , Cancer Vaccines/chemistry , Cancer Vaccines/immunology , Cancer Vaccines/administration & dosage , Tryptophan/chemistry , Tryptophan/analogs & derivatives , Nanoconjugates/chemistry , Mice, Inbred C57BL , Nanoparticles/chemistry , Cell Line, Tumor , Ferric Compounds/chemistry , Nanovaccines
16.
Zhongguo Zhong Yao Za Zhi ; 49(8): 2210-2221, 2024 Apr.
Article in Chinese | MEDLINE | ID: mdl-38812236

ABSTRACT

In this study, J774A.1 macrophages stimulated by lipopolysaccharide(LPS) and adenosine triphosphate(ATP) were used to establish an in vitro model of pyroptosis, and the intervention mechanism of free total rhubarb anthraquinones(FTRAs) on pyroptosis was investigated. J774A.1 macrophages were cultured in vitro, and the experiment was assigned to the control group and groups with different concentrations of LPS(0.25, 0.5, and 1 µg·mL~(-1)) and ATP(1.25, 2.5, and 5 mmol·L~(-1)). An in vitro model of macrophage pyroptosis was established by detecting cell viability through CCK-8, propidium iodide(PI) apoptotic cell staining, lactate dehydrogenase(LDH), interleukin(IL)-18, and tumor necrosis factor(TNF)-α release. Then, J774A.1 macrophages were randomly divided into six groups: blank control group, LPS+ATP group, high-dose FTRA group, and low, medium, and high-dose FTRA pre-protection group. The phenotypic characteristics and key indicators of pyroptosis were detected as the basis for evaluating the effect of FTRAs on pyroptosis induced by LPS and ATP. Western blot and RT-PCR were used to detect the expression levels of protein and mRNA related to the pyroptosis pathway in caspase-1/11 and elucidate the molecular mechanism of the anti-pyroptosis effect. The results showed that the stimulation condition of 0.50 µg·mL~(-1) LPS+5.00 mmol·L~(-1) ATP was the most effective in the in vitro model of macrophage pyroptosis. FTRAs pre-protected cells for 24 h and then can increase cell viability under pyroptosis conditions, alleviate cell damage, lower the positive rate of PI staining, and reduce the release of LDH, IL-18, and TNF-α. FTRAs were able to significantly inhibit the activation of GSDMD proteins and significantly down-regulate the protein expression of the pyroptosis pathway signature molecules, TLR4, NLRP3, cleaved-caspase-1, and cleaved-caspase-11, but they had no significant effect on ASC proteins. FTRAs were also able to significantly inhibit the mRNA expression of caspase-1, caspase-11, and GSDMD. These results indicate that FTRAs have an inhibitory effect on the pyroptosis model induced by LPS and ATP and play an anti-pyroptosis effect by regulating classical and non-classical pyroptosis signaling pathways and reducing the production of inflammatory cytokines.


Subject(s)
Anthraquinones , Macrophages , Pyroptosis , Rheum , Pyroptosis/drug effects , Rheum/chemistry , Animals , Mice , Macrophages/drug effects , Macrophages/metabolism , Macrophages/cytology , Anthraquinones/pharmacology , Anthraquinones/chemistry , Cell Line , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/chemistry , Adenosine Triphosphate/metabolism , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolism , Lipopolysaccharides/pharmacology , Cell Survival/drug effects , Interleukin-18/genetics , Interleukin-18/metabolism
17.
J Agric Food Chem ; 72(22): 12415-12424, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38779960

ABSTRACT

A series of novel 2-Ar-1,2,3-triazole derivatives were designed and synthesized based on our previously discovered active compound 6d against Rhizoctonia solani. Most of these compounds exhibited good antifungal activity against R. solani at a concentration of 25 µg/mL. Based on the results of biological activity, we established a three-dimensional quantitative structure-activity relationship (3D-QSAR) model that guided the synthesis of compound 7y. Compound 7y exhibited superior activity against R. solani (EC50 = 0.47 µg/mL) compared to the positive controls hymexazol (EC50 = 12.80 µg/mL) and tebuconazole (EC50 = 0.87 µg/mL). Furthermore, compound 7y demonstrated better protective activity than the aforementioned two commercial fungicides in both detached leaf assays and greenhouse experiments, achieving 56.21% and 65.75% protective efficacy, respectively, at a concentration of 100 µg/mL. The ergosterol content was determined and molecular docking was performed to explore the mechanism of these active molecules. DFT calculation and MEP analysis were performed to illustrate the results of this study. These results suggest that compound 7y could serve as a novel 2-Ar-1,2,3-triazole lead compound for controlling R. solani.


Subject(s)
Drug Design , Fungicides, Industrial , Molecular Docking Simulation , Plant Diseases , Quantitative Structure-Activity Relationship , Rhizoctonia , Triazoles , Fungicides, Industrial/pharmacology , Fungicides, Industrial/chemistry , Fungicides, Industrial/chemical synthesis , Triazoles/chemistry , Triazoles/pharmacology , Triazoles/chemical synthesis , Rhizoctonia/drug effects , Rhizoctonia/growth & development , Plant Diseases/microbiology , Molecular Structure , Hydrazines/chemistry , Hydrazines/pharmacology
18.
Materials (Basel) ; 17(9)2024 May 02.
Article in English | MEDLINE | ID: mdl-38730943

ABSTRACT

In this study, the CALPHAD approach was employed to model the thermodynamics of the Au-Ge-X (X = In, Sb, Si, Zn) ternary systems, leveraging experimental phase equilibria data and previous assessments of related binary subsystems. The solution phases were modeled as substitutional solutions, and their excess Gibbs energies were expressed using the Redlich-Kister polynomial. Owing to the unavailability of experimental data, the solubility of the third elements in the Au-In, Au-Sb, and Au-Zn binary intermetallic compounds was excluded from consideration. Additionally, stable ternary intermetallic compounds were not reported in the literature and, thus, were not taken into account in the present thermodynamic calculations. Calculations of liquidus projections, isothermal sections, and vertical sections for these ternary systems have been performed, aligning with existing experimental findings. These thermodynamic parameters form a vital basis for creating a comprehensive thermodynamic database for Au-Ge-based alloys, which is essential for the design and development of new high-temperature Pb-free solders.

19.
J Thorac Dis ; 16(4): 2668-2673, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38738227

ABSTRACT

Mediastinal infection caused by anastomotic leak is hard to cure, mainly because the poor drainage at the site of mediastinal infection leads to persistent cavity infection, which in turn becomes a refractory mediastinal abscess cavity after minimally invasive esophagectomy (MIE)-McKeown. Herein, we explored sternocleidomastoid (SCM) muscle flaps and emulsified adipose tissue stromal vascular fraction containing adipose-derived stem-cells to address this issue. We studied 10 patients with esophageal cancer who underwent MIE-McKeown + 2-field lymphadenectomy and developed anastomotic and mediastinal leak and received new technology treatment in the Affiliated Cancer Hospital of Zhengzhou University from June 2018 to March 2022. The clinical data and prognosis of the patients were collected and analyzed. A total of 5 patients received this surgery, and no other complications occurred during the perioperative period. Among the 5 patients, 1 patient was partially cured, and 4 patients were completely cured. During the follow-up 3 months postoperatively, all these 5 patients could eat regular food smoothly, and no relapse of leak and mediastinal infection occurred. The new surgical method has achieved good results in the treatment of anastomotic leak. Compared with the traditional thoracotomy, it is a less invasive and feasible surgical approach, which can be used as a supplement to the effective surgical treatment of cervical anastomotic leak contaminating the mediastinum.

20.
Angew Chem Int Ed Engl ; : e202404747, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38807563

ABSTRACT

Ethynylbenziodoxol(on)es (EB(X)xs) reagents have emerged as useful reagents for peptide/protein modification due to their versatile reactivity and high selectivity. Herein, we report the successful introduction of ethynylbenziodoxoles (EBxs) on different amino acid building blocks (Lys/Orn/Dap), and show their compatibility with both solid phase peptide synthesis (SPPS) and solution phase peptide synthesis (SPS). The selective incorporation of the EBx core into peptide sequences enable efficient macrocyclizations under mild conditions for the synthesis of topologically unique cyclic and bicyclic peptides.

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