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1.
Food Chem X ; 23: 101728, 2024 Oct 30.
Article in English | MEDLINE | ID: mdl-39253017

ABSTRACT

Tartaric acid is one of the characteristic acids in wine, playing a crucial role in wine characteristics. However, superabundant tartaric acid will form insoluble salts and precipitate in the form of crystals, affecting consumers' purchasing appetite. Therefore, tartaric stability is also one of the important indices for controlling the wine quality. At present, the main processing methods for tartaric stability include cold stabilization, ion exchange treatment, electrodialysis and the addition of exogenous components (gum arabic, metatartaric acid, carboxymethyl cellulose, mannoprotein and potassium polyaspartate). This review summarizes and analyzes the origin of tartaric acid in wine, factors influencing the tartaric stability, detection methods, treatments for tartaric stabilization, and the effects of these methods on the sensory quality of wine. Comparing the effects of these methods on wine quality can provide a basis for the further study of tartaric stabilization methods in order to select an appropriate tartaric stabilization method.

2.
Curr Med Res Opin ; : 1-7, 2024 Aug 23.
Article in English | MEDLINE | ID: mdl-39177290

ABSTRACT

OBJECTIVE: Talquetamab is the first-in-class GPRC5DxCD3 bispecific antibody for relapsed/refractory multiple myeloma. Given limited real-world data, this study was conducted with US healthcare providers (HCPs) to understand real-world talquetamab dosing and symptom management. METHODS: In February/March 2024, individual in-depth interviews (IDIs; n = 10) were conducted with HCPs administering talquetamab in real-world settings. A subsequent expert panel (n = 6) further discussed current practices. RESULTS: The IDIs reported a variety of settings for step-up dosing (SUD), including inpatient (n = 5), outpatient (n = 3), and hybrid models (n = 2), with a trend toward shorter SUD length to reduce healthcare resource utilization. Most HCPs used a biweekly (Q2W) schedule in SUD (n = 7) and treatment phases (n = 8). Eight participants explored reducing dose frequency to every 4 weeks (Q4W) in patients following positive disease response to treatment, considering patient convenience and relieving GPRC5D-related symptoms. Panelists recommended symptom management and prophylactic strategies, such as dexamethasone and nystatin mouthwash or zinc and vitamin B complex for oral symptoms, and topical steroids and cosmetic products for skin and nail symptoms. CONCLUSION: This study outlines current real-world practices for talquetamab. Findings indicate variation in the SUD care setting. The 0.8 mg/kg Q2W dosing schedule was most common, although switching to Q4W is a real-world symptom management strategy for some patients with responses to therapy. GPRC5D-related symptom management approaches are evolving; prophylactic use of dexamethasone and nystatin mouthwash or zinc and vitamin B complex may be effective strategies to alleviate oral symptoms. Further real-world evidence is needed to inform optimal dosing schedules while mitigating symptom impact.


Talquetamab is a new treatment that was approved in the United States in 2023 for a type of blood cancer called multiple myeloma. This drug is administered at one of two doses, each of which includes a defined step-up dosing schedule where patients first receive smaller amounts of the drug to help avoid serious side effects. Because talquetamab is new and associated with treatment-related symptoms not normally seen with other multiple myeloma treatments, doctors and patients need more guidance on drug administration and symptom management. In this study, we describe findings from interviews and an expert panel discussion with healthcare professionals who have experience using talquetamab. This study found that most healthcare professionals administered step-up dosing with patients staying overnight in the hospital, while other providers administered these doses during outpatient visits. Most providers administered talquetamab once every 2 weeks after utilizing the associated step-up dosing schedule. Additionally, healthcare providers described transitioning some patients, who had responded positively to treatment, to a less frequent dosing schedule of once per month to help reduce the effect of treatment-related symptoms. Participants in the expert panel described approaches for managing or preventing these symptoms, such as dexamethasone and nystatin mouthwashes or zinc and vitamin B complex for oral symptoms, and topical steroids and cosmetic products for skin and nail symptoms. In summary, this study provides valuable real-world information from healthcare providers who have experience treating patients with multiple myeloma with talquetamab.

3.
J Immunother Cancer ; 12(7)2024 Jul 27.
Article in English | MEDLINE | ID: mdl-39067875

ABSTRACT

BACKGROUND: This study comprehensively investigates the association between the expression of nicotinamide N-methyltransferase (NNMT) and clinical outcomes of urothelial bladder cancer (UBC), as well as the molecular mechanisms by which NNMT in cancer-associated fibroblast (CAF) modulates tumor progression and immunotherapy resistance in UBC. METHODS: Single-cell transcriptomic analyses, immunohistochemical and immunofluorescence assays were performed on bladder cancer samples to validate the relationship between NNMT expression and clinical outcomes. A series of experiments, including chromatin immunoprecipitation assay, liquid chromatography tandem mass spectrometry assay, and CRISPR‒Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats and CRISPR-associated protein 9) knockout, together with in vivo models, have been established to determine the molecular functions of NNMT in CAFs in UBC. RESULTS: We demonstrated that elevated expression of the nicotinamide adenine dinucleotide (NAD+) metabolism enzyme NNMT in CAFs (NNMT+ CAFs) was significantly associated with non-response to programmed death-ligand 1 (PD-L1) blockade immunotherapy in patients with UBC and predicted the unfavorable prognosis of UBC in two independent large cohorts. Targeting NNMT using the inhibitor 5-Amino-1-methylquinolinium iodide significantly reduced tumor growth and enhanced the apoptotic effects of the anti-PD-L1 antibody in UBC mouse models. Mechanistically, NNMT+ CAFs recruit tumor-associated macrophages via epigenetic reprogramming of serum amyloid A (SAA) to drive tumor cell proliferation and confer resistance to programmed death-1/PD-L1 blockade immunotherapy. CONCLUSIONS: NNMT+ CAFs were significantly associated with non-response to PD-L1 blockade immunotherapy in patients with UBC. Elevated NNMT, specifically in CAFs, upregulates SAA expression and enhances the recruitment and differentiation of macrophages in the tumor microenvironment, thereby directly or indirectly promoting tumor progression and conferring resistance to immunotherapies in bladder cancer.


Subject(s)
Cancer-Associated Fibroblasts , Immunotherapy , Macrophages , Nicotinamide N-Methyltransferase , Urinary Bladder Neoplasms , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/immunology , Urinary Bladder Neoplasms/genetics , Humans , Cancer-Associated Fibroblasts/metabolism , Mice , Animals , Nicotinamide N-Methyltransferase/metabolism , Immunotherapy/methods , Macrophages/metabolism , Macrophages/immunology , NAD/metabolism , Drug Resistance, Neoplasm , Female , Disease Progression , Male , Tumor-Associated Macrophages/metabolism , Tumor-Associated Macrophages/immunology
4.
Nat Commun ; 15(1): 6215, 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-39043664

ABSTRACT

Integrating genomics and histology for cancer prognosis demonstrates promise. Here, we develop a multi-classifier system integrating a lncRNA-based classifier, a deep learning whole-slide-image-based classifier, and a clinicopathological classifier to accurately predict post-surgery localized (stage I-III) papillary renal cell carcinoma (pRCC) recurrence. The multi-classifier system demonstrates significantly higher predictive accuracy for recurrence-free survival (RFS) compared to the three single classifiers alone in the training set and in both validation sets (C-index 0.831-0.858 vs. 0.642-0.777, p < 0.05). The RFS in our multi-classifier-defined high-risk stage I/II and grade 1/2 groups is significantly worse than in the low-risk stage III and grade 3/4 groups (p < 0.05). Our multi-classifier system is a practical and reliable predictor for recurrence of localized pRCC after surgery that can be used with the current staging system to more accurately predict disease course and inform strategies for individualized adjuvant therapy.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Neoplasm Recurrence, Local , Humans , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/pathology , Kidney Neoplasms/genetics , Kidney Neoplasms/pathology , Kidney Neoplasms/surgery , Male , Female , Neoplasm Recurrence, Local/genetics , Middle Aged , Aged , Prognosis , Genomics/methods , Adult , Neoplasm Staging , Deep Learning , Disease-Free Survival
5.
Int J Biol Macromol ; 275(Pt 2): 133595, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38960253

ABSTRACT

Bacterial keratitis is among the most prevalent causes of blindness. Currently, the abuse of antibiotics in clinical settings not only lacks bactericidal effects but also readily induces bacterial resistance, making the clinical treatment of bacterial keratitis a significant challenge. In this study, we present an injectable hydrogel (GS-PNH-FF@CuS/MnS) containing self-assembled diphenylalanine dipeptide (FF) and CuS/MnS nanocomposites (CuS/MnS NCs) that destroy bacterial cell walls through a synergistic combination of mild photothermal therapy (PTT), chemodynamic therapy (CDT), ion release chemotherapy, and self-assembled dipeptide contact, thereby eliminating Pseudomonas aeruginosa. Under 808 nm laser irradiation, the bactericidal efficiency of GS-PNH-FF@CuS/MnS hydrogel against P. aeruginosa in vitro reach up to 96.97 %. Furthermore, GS-PNH-FF@CuS/MnS hydrogel is applied topically to kill bacteria, reduce inflammation, and promote wound healing. Hematoxylin-eosin (H&E) staining, Masson staining, immunohistochemistry and immunofluorescence staining are used to evaluate the therapeutic effect on infected rabbit cornea models in vivo. The GS-PNH-FF@CuS/MnS demonstrate good biocompatibility with human corneal epithelial cells and exhibit no obvious eyes side effects. In conclusion, the GS-PNH-FF@CuS/MnS hydrogel in this study provides an effective and safe treatment strategy for bacterial keratitis through a multimodal approach.


Subject(s)
Alginates , Anti-Bacterial Agents , Gelatin , Hydrogels , Keratitis , Pseudomonas aeruginosa , Keratitis/drug therapy , Keratitis/microbiology , Hydrogels/chemistry , Animals , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Rabbits , Pseudomonas aeruginosa/drug effects , Gelatin/chemistry , Alginates/chemistry , Humans , Injections , Photothermal Therapy/methods
6.
Int J Biol Macromol ; 276(Pt 1): 133733, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39002905

ABSTRACT

Chitosan and its derivatives are ideal nasal vaccine adjuvant to deliver antigens to immune cells. Previously, we successfully used a chitosan derivative, O-(2-Hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (O-HTCC), and a ß-glucan derivative, curdlan sulfate (CS), to prepare a nanoparticle adjuvant CS/O-HTCC which could deliver ovalbumin to antigen presenting cells (APCs) through nasal inhalation. In this article, we used SARS-CoV-2 spike receptor binding domain (S-RBD) as the antigen and CS/O-HTCC nanoparticles as the adjuvant to develop a nasal mucosal protein subunit vaccine, CS/S-RBD/O-HTCC. The humoral immunity, cell-mediated immunity and mucosal immunity induced by vaccines were evaluated. The results showed that CS/S-RBD/O-HTCC could induce desirable immunization with single or bivalent antigen through nasal inoculation, giving one booster vaccination with mutated S-RBD (beta) could bring about a broad cross reaction with ancestral and different mutated S-RBD, and vaccination of the BALB/c mice with CS/S-RBD/O-HTCC containing S-RBD mix antigens (ancestral and omicron) could induce the production of binding and neutralizing antibodies against both of the two antigens. Our results indicate that CS/O-HTCC is a promising nasal mucosal adjuvant to prepare protein subunit vaccine for both primary and booster immunization, and the adjuvant is suitable for loading more than one antigen for preparing multivalent vaccines.


Subject(s)
Adjuvants, Immunologic , Administration, Intranasal , COVID-19 , Chitosan , Mice, Inbred BALB C , Nanoparticles , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Vaccines, Subunit , beta-Glucans , Chitosan/chemistry , Animals , Nanoparticles/chemistry , beta-Glucans/chemistry , beta-Glucans/immunology , SARS-CoV-2/immunology , Vaccines, Subunit/immunology , Mice , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Adjuvants, Immunologic/pharmacology , COVID-19/prevention & control , COVID-19/immunology , Female , COVID-19 Vaccines/immunology , COVID-19 Vaccines/chemistry , Antibodies, Viral/immunology , Immunity, Mucosal/drug effects , Mutation , Antibodies, Neutralizing/immunology , Drug Carriers/chemistry , Adjuvants, Vaccine/chemistry , Humans
7.
Front Vet Sci ; 11: 1418101, 2024.
Article in English | MEDLINE | ID: mdl-38948672

ABSTRACT

Feline chronic gingivostomatitis (FCGS) is an ulcerative and/or proliferative disease that typically affects the palatoglossal folds. Because of its unknown pathogenesis and long disease course, it is difficult to treat and has a high recurrence rate. Most of the bacteria in the oral microbiota exist in the mouth symbiotically and maintain a dynamic balance, and when the balance is disrupted, they may cause disease. Disturbance of the oral microbiota may play an important role in the development of FCGS. In this study, the medical records of 3109 cats in three general pet hospitals in Xi 'an were collected. Sixty-one cats with FCGS were investigated via questionnaires, routine oral examinations and laboratory examinations. Oral microbiota samples were collected from 16 FCGS-affected cats, and microbial species were identified by 16S rDNA sequencing. The results showed that the incidence of FCGS had no significant correlation with age, sex or breed. However, the incidence of FCGS was associated with immunization, a history of homelessness and multicat rearing environments. The number of neutrophils and the serum amyloid A concentration were increased, and the percentage of cells positive for calicivirus antigen was high in all cases. All the cats had different degrees of dental calculus, and there were problems such as loss of alveolar bone or tooth resorption. Compared with those in healthy cats, the bacterial diversity and the abundance of anaerobic bacteria were significantly increased in cats with FCGS. Porphyromonas, Treponemas and Fusobacterium were abundant in the mouths of the affected cats and may be potential pathogens of FCGS. After tooth extraction, a shift could be seen in the composition of the oral microbiota in cats with FCGS. An isolated bacteria obtained from the mouths of the affected cats was homologous to P. gulae. Both the identified oral microbiota and the isolated strain of the cats with FCGS had high sensitivity to enrofloxacin and low sensitivity to metronidazole. This study provides support to current clinical criteria in diagnosing FCGS and proposes a more suitable antibiotic therapy.

8.
BMC Genomics ; 25(1): 564, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38840037

ABSTRACT

Mesenchymal Stem Cells are ideal seed cells for tissue repair and cell therapy and have promising applications in regenerative medicine and tissue engineering. Using Platelet-Rich Plasma as an adjuvant to create and improve the microenvironment for Mesenchymal Stem Cells growth can enhance the biological properties of Mesenchymal Stem Cells and improve the efficacy of cell therapy. However, the mechanism by which Platelet-Rich Plasma improves the biological performance of Mesenchymal Stem Cells is still unknown. In this study, by examining the effects of Platelet-Rich Plasma on the biological performance of Mesenchymal Stem Cells, combined with multiomics analysis (Transcriptomics, Proteomics and Metabolomics) and related tests, we analyzed the specific pathways, related mechanisms and metabolic pathways of Platelet-Rich Plasma to improve the biological performance of Mesenchymal Stem Cells. In an in vitro cell culture system, the biological performance of Mesenchymal Stem Cells was significantly improved after replacing Foetal Bovine Serum with Platelet-Rich Plasma, and the genes (ESM1, PDGFB, CLEC7A, CCR1 and ITGA6 et al.) related to cell proliferation, adhesion, growth, migration and signal transduction were significantly upregulated. Platelet-Rich Plasma can enhance the secretion function of MSC exosomes, significantly upregulate many proteins related to tissue repair, immune regulation and anti-infection, and enhance the repair effect of exosomes on skin injury. After replacing Foetal Bovine Serum with Platelet-Rich Plasma, Mesenchymal Stem Cells underwent metabolic reprogramming, the metabolism of amino acids and fatty acids and various signaling pathways were changed, the anabolic pathways of various proteins were enhanced. These results provide a theoretical and technical reference for optimizing the Mesenchymal Stem Cells culture system, improving the biological characteristics and clinical application effects of Mesenchymal Stem Cells.


Subject(s)
Cell Proliferation , Mesenchymal Stem Cells , Platelet-Rich Plasma , Proteomics , Mesenchymal Stem Cells/metabolism , Mesenchymal Stem Cells/cytology , Platelet-Rich Plasma/metabolism , Humans , Metabolomics , Animals , Cells, Cultured , Gene Expression Profiling , Exosomes/metabolism , Multiomics
10.
Lancet Oncol ; 25(7): 843-852, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38852601

ABSTRACT

BACKGROUND: PD-1 blockade is highly efficacious for mismatch repair-deficient colorectal cancer in both metastatic and neoadjuvant settings. We aimed to explore the activity and safety of neoadjuvant therapy with PD-1 blockade plus an angiogenesis inhibitor and the feasibility of organ preservation in patients with locally advanced mismatch repair-deficient colorectal cancer. METHODS: We initiated a single-arm, open-label, phase 2 trial (NEOCAP) at Sun Yat-sen University Cancer Center and the Provincial Hospital of Traditional Chinese Medicine, Guangzhou, China. Patients aged 18-75 years with untreated mismatch repair-deficient or microsatellite instability-high or POLE/POLD1-mutated locally advanced colorectal cancer (cT3 or N+ for rectal cancer, and T3 with invasion ≥5mm or T4, with or without N+ for colon cancer) and an Eastern Cooperative Oncology Group performance score of 0-1 were enrolled and given 200 mg camrelizumab intravenously on day 1 and 250 mg apatinib orally from day 1-14, every 3 weeks for 3 months followed by surgery or 6 months if patients did not have surgery. Patients who had a clinical complete response did not undergo surgery and proceeded with a watch-and-wait approach. The primary endpoint was the proportion of patients with a pathological or clinical complete response. Eligible enrolled patients who received at least one cycle of neoadjuvant treatment and had at least one tumour response assessment following the baseline assessment were included in the activity analysis, and patients who received at least one dose of study drug were included in the safety analysis. The study is registered with ClinicalTrials.gov (NCT04715633) and is ongoing. FINDINGS: Between Sept 29, 2020, and Dec 15, 2022, 53 patients were enrolled; one patient was excluded from the activity analysis because they were found to be mismatch repair-proficient and microsatellite-stable. 23 (44%) patients were female and 29 (56%) were male. The median follow-up was 16·4 (IQR 10·5-23·5) months. 28 (54%; 95% CI 35-68) patients had a clinical complete response and 24 of these patients were managed with a watch-and-wait approach, including 20 patients with colon cancer and multiple primary colorectal cancer. 23 (44%) of 52 patients underwent surgery for the primary tumour, and 14 (61%; 95% CI 39-80) had a pathological complete response. 38 (73%; 95% CI 59-84) of 52 patients had a complete response. Grade 3-5 adverse events occurred in 20 (38%) of 53 patients; the most common were increased aminotransferase (six [11%]), bowel obstruction (four [8%]), and hypertension (four [8%]). Drug-related serious adverse events occurred in six (11%) of 53 patients. One patient died from treatment-related immune-related hepatitis. INTERPRETATION: Neoadjuvant camrelizumab plus apatinib show promising antitumour activity in patients with locally advanced mismatch repair-deficient or microsatellite instability-high colorectal cancer. Immune-related adverse events should be monitored with the utmost vigilance. Organ preservation seems promising not only in patients with rectal cancer, but also in those with colon cancer who have a clinical complete response. Longer follow-up is needed to assess the oncological outcomes of the watch-and-wait approach. FUNDING: The National Natural Science Foundation of China, Guangdong Basic and Applied Basic Research Foundation, and the Cancer Innovative Research Program of Sun Yat-sen University Cancer Center. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.


Subject(s)
Antibodies, Monoclonal, Humanized , Antineoplastic Combined Chemotherapy Protocols , Colorectal Neoplasms , DNA Mismatch Repair , Microsatellite Instability , Neoadjuvant Therapy , Pyridines , Humans , Middle Aged , Female , Male , Neoadjuvant Therapy/adverse effects , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Pyridines/administration & dosage , Pyridines/adverse effects , Pyridines/therapeutic use , Aged , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/adverse effects , Antibodies, Monoclonal, Humanized/therapeutic use , Young Adult , Immune Checkpoint Inhibitors/adverse effects , Immune Checkpoint Inhibitors/therapeutic use , Immune Checkpoint Inhibitors/administration & dosage , Adolescent
11.
Metabolites ; 14(5)2024 May 08.
Article in English | MEDLINE | ID: mdl-38786749

ABSTRACT

Transcriptomics and metabolomics offer distinct advantages in investigating the differentially expressed genes and cellular entities that have the greatest influence on end-phenotype, making them crucial techniques for studying plant quality and environmental responses. While numerous relevant articles have been published, a comprehensive summary is currently lacking. This review aimed to understand the global and longitudinal research trends of transcriptomics and metabolomics in plant quality and environmental response (TMPQE). Utilizing bibliometric methods, we presented a comprehensive science mapping of the social structure, conceptual framework, and intellectual foundation of TMPQE. We uncovered that TMPQE research has been categorized into three distinct stages since 2020. A citation analysis of the 29 most cited articles, coupled with a content analysis of recent works (2020-2023), highlight five potential research streams in plant quality and environmental responses: (1) biosynthetic pathways, (2) abiotic stress, (3) biotic stress, (4) development and ripening, and (5) methodologies and tools. Current trends and future directions are shaped by technological advancements, species diversity, evolving research themes, and an environmental ecology focus. Overall, this review provides a novel and comprehensive perspective to understand the longitudinal trend on TMPQE.

12.
Toxics ; 12(5)2024 May 05.
Article in English | MEDLINE | ID: mdl-38787114

ABSTRACT

Tert-butylhydroquinone (tBHQ) has emerged as a promising candidate for mitigating the adverse effects of T-2-induced reproductive toxicity. The protective effects of tBHQ on rat sperm quality, testicular injury, apoptosis, and inflammation induced by T-2 toxin exposure were investigated. Histopathological examination of testicular tissues revealed severe damage in the T-2-treated group, characterized by disorganized germ cell arrangement, thinning of the convoluted seminiferous tubule walls, and significant cellular necrosis. However, tBHQ administration, either as a preventive or therapeutic measure, mitigated this structural damage. Image analysis confirmed an increase in the cross-sectional area and height of the convoluted seminiferous tubules in the tBHQ-treated groups compared to the T-2-treated group (p < 0.05), indicating tBHQ's efficacy in alleviating testicular damage. Additionally, tBHQ treatment significantly inhibited T-2-induced apoptosis of testicular tissue cells, as evidenced by the results showing reduced apoptotic cell counts and downregulation of the BAX/BCL2 ratio and caspase-3 expression (p < 0.05). tBHQ significantly increased the concentrations of the antioxidant factors SOD, CAT, TAC, and GSH-PX. Furthermore, tBHQ attenuated the inflammatory response induced by T-2 exposure, as indicated by the decreased mRNA expression of the proinflammatory cytokines Tnf, Il1, and Il10 in testicular tissue (p < 0.05). Additionally, tBHQ treatment alleviated the decline in serum testosterone induced by the T-2 and promoted testosterone synthesis gene expression, including for the genes 17ß-HSD and Cyp11a1, in rat testes (p < 0.05). These findings underscore tBHQ's role as a therapeutic agent combatting T-2-induced reproductive toxicity, highlighting its antioxidative, anti-apoptotic, and anti-inflammatory properties. Further elucidation of tBHQ's mechanisms of action may offer novel strategies for preventing and treating reproductive disorders induced by environmental toxins.

13.
Nat Commun ; 15(1): 3768, 2024 May 04.
Article in English | MEDLINE | ID: mdl-38704409

ABSTRACT

Accurate intraoperative differentiation of primary central nervous system lymphoma (PCNSL) remains pivotal in guiding neurosurgical decisions. However, distinguishing PCNSL from other lesions, notably glioma, through frozen sections challenges pathologists. Here we sought to develop and validate a deep learning model capable of precisely distinguishing PCNSL from non-PCNSL lesions, especially glioma, using hematoxylin and eosin (H&E)-stained frozen whole-slide images. Also, we compared its performance against pathologists of varying expertise. Additionally, a human-machine fusion approach integrated both model and pathologic diagnostics. In external cohorts, LGNet achieved AUROCs of 0.965 and 0.972 in distinguishing PCNSL from glioma and AUROCs of 0.981 and 0.993 in differentiating PCNSL from non-PCNSL lesions. Outperforming several pathologists, LGNet significantly improved diagnostic performance, further augmented to some extent by fusion approach. LGNet's proficiency in frozen section analysis and its synergy with pathologists indicate its valuable role in intraoperative diagnosis, particularly in discriminating PCNSL from glioma, alongside other lesions.


Subject(s)
Central Nervous System Neoplasms , Deep Learning , Frozen Sections , Glioma , Lymphoma , Humans , Central Nervous System Neoplasms/pathology , Central Nervous System Neoplasms/surgery , Central Nervous System Neoplasms/diagnosis , Lymphoma/pathology , Lymphoma/diagnosis , Lymphoma/surgery , Glioma/surgery , Glioma/pathology , Proof of Concept Study , Male , Female , Diagnosis, Differential , Middle Aged , Aged , Intraoperative Period
14.
J Plant Res ; 137(4): 575-587, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38652407

ABSTRACT

Eomecon chionantha Hance, an endemic species in China, has a long medical history in Chinese ethnic minority medicine and is known for its anti-inflammatory and analgesic effects. However, studies of E. chionantha are lacking. In this study, we investigated the characteristics of the E. chionantha chloroplast genome and determined the taxonomic position of E. chionantha in Papaveraceae via phylogenetic analysis. In addition, we determined molecular markers to identify E. chionantha at the molecular level by comparing the chloroplast genomes of E. chionantha and its closely related species. The complete chloroplast genomic information indicated that E. chionantha chloroplast DNA (178,808 bp) contains 99 protein-coding genes, 8 rRNAs, and 37 tRNAs. Meanwhile, we were able to identify a total of 54 simple sequence repeats through our analysis. Our findings from the phylogenetic analysis suggest that E. chionantha shares a close relationship with four distinct species, namely Macleaya microcarpa, Coreanomecon hylomeconoides, Hylomecon japonica, and Chelidonium majus. Additionally, using the Kimura two-parameter model, we successfully identified five hypervariable regions (ycf4-cemA, ycf3-trnS-GGA, trnC-GCA-petN, rpl32-trnL-UAG, and psbI-trnS-UGA). To the best of our knowledge, this is the first report of the complete chloroplast genome of E. chionantha, providing a scientific reference for further understanding of E. chionantha from the perspective of the chloroplast genome and establishing a solid foundation for the future identification, taxonomic determination and evolutionary analysis of this species.


Subject(s)
Genome, Chloroplast , Phylogeny , Genome, Chloroplast/genetics , China , Papaveraceae/genetics , DNA, Chloroplast/genetics , Microsatellite Repeats/genetics , Sequence Analysis, DNA
15.
Front Vet Sci ; 11: 1342930, 2024.
Article in English | MEDLINE | ID: mdl-38371599

ABSTRACT

This study aimed to determine the effect of prostaglandin F2α (PGF2α) analog (D-cloprostenol sodium and DL-cloprostenol sodium) administration on the milk yield of multiparous sows (MS) and piglet growth performance. In total, 320 Landrace×Yorkshire parturient MS were randomly divided into three groups on day 115 of pregnancy: without treatment (N = 50), with 75 µg D-cloprostenol sodium (N = 137), and with 200 µg DL-cloprostenol sodium (N = 133). After delivery, the sows treated with D-cloprostenol sodium and DL-cloprostenol sodium were randomly allocated into three subgroups, respectively: (i) no additional treatment after farrowing; (ii) administration of cloprostenol sodium at 3 h and 5 days after farrowing; and (iii) administration of cloprostenol sodium at 3 h, 5 days, and 10 days after farrowing. Cloprostenol sodium effectively induced sows to synchronize parturition approximately 23 h after administration and increased the daytime delivery rates (p < 0.05). Compared with DL-cloprostenol sodium, D-cloprostenol sodium shortened the farrowing duration and birth interval of sows for inducing farrowing (p < 0.05). Moreover, we observed that a single administration of both D-cloprostenol sodium and DL-cloprostenol sodium a day before delivery significantly reduced the rates of stillborn piglets type II in MS (p < 0.05). Compared to no treatment and single treatment with cloprostenol sodium, quartic treatments with cloprostenol sodium significantly increased the daily feed intake of MS, litter weight after weaning, and average daily gain of piglets (p < 0.05). Cloprostenol sodium improved the 21-day milk yield, with D-cloprostenol sodium showing the best effect, which increased lactation ability by 30.30% (176.72 kg vs. 135.63 kg) (p < 0.05). DL-cloprostenol sodium followed closely, increasing lactation ability by approximately 25.00% (169.71 kg vs. 135.63 kg) (p < 0.05). During lactation, sows administered with D-cloprostenol sodium observed increased serum prolactin levels. Compared to untreated sows, the sows administered with D-cloprostenol sodium and multiple DL-cloprostenol sodium visibly shortened the weaning-to-estrus interval (WEI) and weaning-to-service interval (WSI) (p < 0.05). Furthermore, quartic injections of D-cloprostenol sodium resulted in an 18 percentage point increase in the pregnancy rate of breeding sows compared to controls (82.61% vs. 64.58%) (p > 0.05). In summary, cloprostenol sodium could enhance the reproductive performance of MS, particularly in terms of lactation performance. Additionally, the effect of quartic injections of D-cloprostenol sodium was the most pronounced.

16.
Langmuir ; 40(10): 5488-5498, 2024 Mar 12.
Article in English | MEDLINE | ID: mdl-38423602

ABSTRACT

Improving the ionic rectification in nanochannels enables versatile applications such as biosensors, energy harvesting, and fluidic diodes. While previous work mostly focused on the effect of channel geometry and surface charge, in this work via a series of molecular dynamics simulations, we find a striking phenomenon that the ionic current rectification (ICR) ratio in Janus graphene oxide (GO) channels can be tremendously promoted by lateral electric fields. First, under a given axial electric field, an additional lateral electric field can improve the ICR ratio by several times to an order, depending on the channel symmetry. The symmetric channel has an obviously greater ICR ratio because it maintains a more pronounced ion transport disparity at opposite axial fields. The underlying mechanism for the function of the lateral electric field is that it promotes the lateral migration of ions and thus amplifies the ion-residue electrostatic interaction at opposite axial fields, enlarging the ion dynamical difference. Furthermore, for different axial electric fields, the ICR ratio can always be improved by lateral electric fields (up to two orders), suggesting that the ICR improvement is universal. Our results demonstrate that applying a lateral electric field could be a new method to improve the rectification performance of nanochannels, providing valuable guidance for the design of efficient ionic diode devices.

17.
Sci Total Environ ; 919: 170801, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38340858

ABSTRACT

Addressing soil salinization and implementing sustainable practices for cultivating cash crops on saline-alkali land is a prominent global challenge. Cynomorium songaricum is an important salt-alkali tolerant medicinal plant capable of adapting to saline-alkali environments. In this study, two typical ecotypes of C. songaricum from the desert-steppe (DS) and saline-alkali land (SAL) habitats were selected. Through the integration of multi-omics with machine learning, the rhizosphere microbial communities, genetic maps, and metabolic profiles of two ecotypes were created and the crucial factors for the adaptation of C. songaricum to saline-alkali stress were identified, including 7 keystone OTUs (i.e. Novosphingobium sp., Sinorhizobium meliloti, and Glycomyces sp.), 5 core genes (cell wall-related genes), and 10 most important metabolites (i.e. cucurbitacin D and 3-Hydroxybutyrate) were identified. Our results indicated that under saline-alkali environments, the microbial competition might become more intense, and the microbial community network had the simple but stable structure, accompanied by the changes in the gene expression related to cell wall for adaptation. However, this regulation led to the reduction in active ingredients, such as the accumulation of flavonoids and organic acid, and enhanced the synthesis of bitter substances (cucurbitacin D), resulting in the decrease in the quality of C. songaricum. Therefore, compared to the SAL ecotype, the DS was more suitable for the subsequent development of medicinal and edible products of C. songaricum. Furthermore, to explore the reasons for this quality variation, we constructed a comprehensive microbial-genetic-metabolic regulatory network, revealing that the metabolism of C. songaricum was primarily influenced by genetic factors. These findings not only offer new insights for future research into plant salt-alkali tolerance strategies but also provide a crucial understanding for cultivating high-quality medicinal plants.


Subject(s)
Cynomorium , Microbiota , Triterpenes , Transcriptome , Cynomorium/chemistry , Cynomorium/physiology , Alkalies , Metabolome
18.
iScience ; 27(3): 109243, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38420592

ABSTRACT

Accurate tumor diagnosis by pathologists relies on identifying specific morphological characteristics. However, summarizing these unique morphological features in tumor classifications can be challenging. Although deep learning models have been extensively studied for tumor classification, their indirect and subjective interpretation obstructs pathologists from comprehending the model and discerning the morphological features accountable for classifications. In this study, we introduce a new approach utilizing Style Generative Adversarial Networks, which enables a direct interpretation of deep learning models to detect significant morphological characteristics within datasets representing patients with deficient mismatch repair/microsatellite instability-high gastric cancer. Our approach effectively identifies distinct morphological features crucial for tumor classification, offering valuable insights for pathologists to enhance diagnostic accuracy and foster professional growth.

19.
Plants (Basel) ; 13(2)2024 Jan 08.
Article in English | MEDLINE | ID: mdl-38256727

ABSTRACT

Many customers prefer goji berry pulp, well-known for its high nutritional content, over fresh goji berries. However, there is limited research on its sensory lexicon and distinctive flavor compounds. This study focused on developing a sensory lexicon for goji berry pulp and characterizing its aroma by sensory and instrumental analysis. Sensory characteristics of goji berry pulp were evaluated by our established lexicon. A total of 83 aromatic compounds in goji berry pulp were quantified using HS-SPME-GC-Orbitrap-MS. By employing OAV in combination, we identified 17 aroma-active compounds as the key ingredients in goji berry pulp. Then, we identified the potentially significant contributors to the aroma of goji berry pulp by combining principal component analysis and partial least squares regression (PLSR) models of aroma compounds and sensory attributes, which included 3-ethylphenol, methyl caprylate, 2-hydroxy-4-methyl ethyl valerate, benzeneacetic acid, ethyl ester, hexanal, (E,Z)-2,6-nonadienal, acetylpyrazine, butyric acid, 2-ethylhexanoic acid, 2-methyl-1-propanol, 1-pentanol, phenylethyl alcohol, and 2-nonanone. This study provides a theoretical basis for improving the quality control and processing technology of goji berry pulp.

20.
ACS Appl Mater Interfaces ; 16(2): 2659-2671, 2024 Jan 17.
Article in English | MEDLINE | ID: mdl-38166374

ABSTRACT

Improving the desalination performance of membranes is always in the spotlight of scientific research; however, Janus channels with polarized surface charge as nanofiltration membranes are still unexplored. In this work, using molecular dynamics simulations, we demonstrate that Janus graphene oxide (GO) channels with appropriate geometry and surface charge can serve as highly efficient nanofiltration membranes. We observe that the water permeability of symmetric Janus GO channels is significantly superior to that of asymmetric channels without sacrificing much ion rejection, owing to weakened ion blockage and electrostatic effects. Furthermore, in symmetric Janus GO channels, the transport of water and ions is sensitive to the charge polarity of the channel inner surface, which is realized by tuning the ratio of cationic and anionic functionalization. Specifically, with the increase in cationic functionalization, the water flux decreases monotonously, while ion rejection displays an interesting maximum behavior that indicates desalination optimization. Moreover, the trade-off between water permeability and ion rejection suggests that the Janus GO channels have an excellent desalination potential and are highly tunable according to the specific water treatment requirements. Our work sheds light on the key role of channel geometry and charge polarity in the desalination performance of Janus GO channels, which paves the way for the design of novel desalination devices.

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