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1.
Cell Insight ; 3(2): 100147, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38344386

RESUMO

The stimulator of interferon genes (STING) plays a pivotal role in orchestrating innate immunity, and dysregulated activity of STING has been implicated in the pathogenesis of autoimmune diseases. Recent findings suggest that bacterial infection activates STING, relieving ER stress, and triggers non-canonical autophagy by spatially regulating STX17. Despite these insights, the precise mechanism governing the dynamics of autophagosome fusion elicited by STING remains unclear. In this study, we demonstrate that dynamic STING activation guides the autophagy flux, mirroring the trajectory of canonical autophagy adaptors. STING engages in a physical interaction with STX17, and agonist-induced phosphorylation or degradation alleviates STING's inhibitory effects on the assembly of the STX17-SNAP29-VAMP8 complex. Consistent with these findings, degradation-deficient mutants hinder autophagy flux by impeding STX17-mediated autophagosome-lysosome fusion. Moreover, STING mutants associated with lupus disrupt the assembly of the STX17-SNAP29-VAMP8 complex and autophagy process, which lead to persistent STING activation and elevated IFN-ß production. Our results highlight that the intracellular trajectory of STING, coupled with autophagy flux, guides the assembly and membrane fusion of the STX17-SNAP29-VAMP8 complex, ensuring the accurate regulation of innate immunity.

2.
Food Chem ; 444: 138673, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38330615

RESUMO

This study applied and validated the Multiplex-PCR method to identify the authenticity of duck blood and four common adulterated animal blood varieties. To this end, the genomic DNAs of duck blood and its counterfeit products were extracted using an efficient high-throughput extraction method. Specific primers were designed using the cytochrome b gene. The reaction system and conditions of a multiplex (namely, Five-plex) PCR were optimized, and the proposed methodology was verified, proving its good specificity, repeatability, and sensitivity. The Five-plex PCR system detected nine duck blood samples sold in the local market, revealing the adulteration of duck blood products. The Multiplex-PCR system can accurately and quickly detect adulterated animal blood in duck blood products, effectively finding counterfeits and identifying the authenticity of genuine duck blood products.

3.
J Colloid Interface Sci ; 661: 870-878, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38330659

RESUMO

Metallic lithium (Li) is highly desirable for Li battery anodes due to its unique advantages. However, the growth of Li dendrites poses challenges for commercialization. To address this issue, researchers have proposed various three-dimensional (3D) current collectors. In this study, the selective modification of a 3D Cu foam scaffold with lithiophilic elements was explored to induce controlled Li deposition. The Cu foam was selectively modified with Ag and Sn to create uniform Cu foam (U-Cu) and gradient lithiophilic Cu foam (G-Cu) structures. Density Functional Theory (DFT) calculations revealed that Ag exhibited a stronger binding energy with Li compared to Sn, indicating superior Li induction capabilities. Electrochemical testing demonstrated that the half cell with the G-Cu@Ag electrode exhibited excellent cycling stability, maintaining 550 cycles with an average Coulombic efficiency (CE) of 97.35%. This performance surpassed that of both Cu foam and G-Cu@Sn. The gradient modification of the current collectors improved the utilization of the 3D scaffold and prevented Li accumulation at the top of the scaffold. Overall, the selective modification of the 3D Cu foam scaffold with lithiophilic elements, particularly Ag, offers promising prospects for mitigating Li dendrite growth and enhancing the performance of Li batteries.

4.
J Leukoc Biol ; 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38334307

RESUMO

Poly (ADP ribose) polymerase family member 11(PARP11) has important immune regulatory functions in viral infection and tumor immune response. Particularly, PARP11 showed protumor activities in multiple preclinical murine models. However, no systematic pan-cancer analysis has been conducted to explore PARP11 function. In this study we used multiple databases to assess PARP11 expression, which associations with clinical outcomes, immune checkpoint factors, prognostic significance, genomic characteristics, and immunological aspects. The analysis revealed varying expression levels of PARP11 across different cancer types and a significant correlation between its expression and immune cell infiltration. Insights from the CellMiner database suggest a strong link between PARP11 expression and sensitivity to anticancer drugs, highlighting its potential as a therapeutic target. Moreover, PARP11 expression correlates with patient survival during anti-PD1 and anti-CTLA4 treatments, suggested that PARP11 would be a predictor of immune checkpoint inhibitor (ICI) treatment. In summary, PARP11 would be a potential immunoregulatory target and a diagnosis and prognosis marker for certain types of cancers. The detailed mechanisms of PARP11 in tumor immune responses need to be further investigated.

5.
Front Public Health ; 12: 1148705, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38327578

RESUMO

Objectives: The present study analyzed the impact of the COVID-19 pandemic on the prevalence and incidence of new leprosy cases, as well as the diversity, distribution, and temporal transmission of Mycobacterium leprae strains at the county level in leprae-endemic provinces in Southwest China. Methods: A total of 219 new leprosy cases during two periods, 2018-2019 and 2020-2021, were compared. We genetically characterized 83 clinical isolates of M. leprae in Guizhou using variable number tandem repeats (VNTRs) and single nucleotide polymorphisms (SNPs). The obtained genetic profiles and cluster consequences of M. leprae were compared between the two periods. Results: There was an 18.97% decrease in the number of counties and districts reporting cases. Considering the initial months (January-March) of virus emergence, the number of new cases in 2021 increased by 167% compared to 2020. The number of patients with a delay of >12 months before COVID-19 (63.56%) was significantly higher than that during COVID-19 (48.51%). Eighty-one clinical isolates (97.60%) were positive for all 17 VNTR types, whereas two (2.40%) clinical isolates were positive for 16 VNTR types. The (GTA)9, (TA)18, (TTC)21 and (TA)10 loci showed higher polymorphism than the other loci. The VNTR profile of these clinical isolates generated five clusters, among which the counties where the patients were located were adjacent or relatively close to each other. SNP typing revealed that all clinical isolates possessed the single SNP3K. Conclusion: COVID-19 may have a negative/imbalanced impact on the prevention and control measures of leprosy, which could be a considerable fact for official health departments. Isolates formed clusters among counties in Guizhou, indicating that the transmission chain remained during the epidemic and was less influenced by COVID-19 preventative policies.


Assuntos
COVID-19 , Hanseníase , Humanos , Mycobacterium leprae/genética , Pandemias , DNA Bacteriano/genética , COVID-19/epidemiologia , Hanseníase/epidemiologia , Hanseníase/microbiologia , China/epidemiologia
6.
World J Gastrointest Surg ; 16(1): 85-94, 2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-38328326

RESUMO

BACKGROUND: Gastric cancer is one of the most common malignant tumors in the digestive system, ranking sixth in incidence and fourth in mortality worldwide. Since 42.5% of metastatic lymph nodes in gastric cancer belong to nodule type and peripheral type, the application of imaging diagnosis is restricted. AIM: To establish models for predicting the risk of lymph node metastasis in gastric cancer patients using machine learning (ML) algorithms and to evaluate their predictive performance in clinical practice. METHODS: Data of a total of 369 patients who underwent radical gastrectomy at the Department of General Surgery of Affiliated Hospital of Xuzhou Medical University (Xuzhou, China) from March 2016 to November 2019 were collected and retrospectively analyzed as the training group. In addition, data of 123 patients who underwent radical gastrectomy at the Department of General Surgery of Jining First People's Hospital (Jining, China) were collected and analyzed as the verification group. Seven ML models, including decision tree, random forest, support vector machine (SVM), gradient boosting machine, naive Bayes, neural network, and logistic regression, were developed to evaluate the occurrence of lymph node metastasis in patients with gastric cancer. The ML models were established following ten cross-validation iterations using the training dataset, and subsequently, each model was assessed using the test dataset. The models' performance was evaluated by comparing the area under the receiver operating characteristic curve of each model. RESULTS: Among the seven ML models, except for SVM, the other ones exhibited higher accuracy and reliability, and the influences of various risk factors on the models are intuitive. CONCLUSION: The ML models developed exhibit strong predictive capabilities for lymph node metastasis in gastric cancer, which can aid in personalized clinical diagnosis and treatment.

7.
Chem Sci ; 15(5): 1692-1699, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38303953

RESUMO

On account of the scarcity of molecules with a satisfactory second near-infrared (NIR-II) response, the design of high-performance organic NIR photothermal materials has been limited. Herein, we investigate a cocrystal incorporating tetrathiafulvalene (TTF) and tetrachloroperylene dianhydride (TCPDA) components. A stable radical was generated through charge transfer from TTF to TCPDA, which exhibits strong and wide-ranging NIR-II absorption. The metal-free TTF-TCPDA cocrystal in this research shows high photothermal conversion capability under 1064 nm laser irradiation and clear photothermal imaging. The remarkable conversion ability-which is a result of twisted components in the cocrystal-has been demonstrated by analyses of single crystal X-ray diffraction, photoluminescence and femtosecond transient absorption spectroscopy as well as theoretical calculations. We have discovered that space charge separation and the ordered lattice in the TTF-TCPDA cocrystal suppress the radiative decay, while simultaneously strong intermolecular charge transfer enhances the non-radiative decay. The twisted TCPDA component induces rapid charge recombination, while the distorted configuration in TTF-TCPDA favors an internal non-radiative pathway. This research has provided a comprehensive understanding of the photothermal conversion mechanism and opened a new way for the design of advanced organic NIR-II photothermal materials.

8.
Nanoscale ; 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38303672

RESUMO

Porous carbon materials with oriented porosity are very useful in ion batteries, but their high cost and complex fabrication hinder their wide application. In this paper, we used cheap and water-soluble NaHCO3 grains to prepare unique porous carbon with an orderly arranged tube array via one-step carbonization. During the preparation process, a novel self-blowing mold of salt templates was discovered for the first time, and the resulting numerous high-speed gas jets can act as gas state templates to induce the formation of the oriented porous carbon into a mesoscale tube array with rich micropores. Besides, the amount of CO functional groups has been enhanced greatly by the chemical activation of H2O and CO2 derived from the decomposition of NaHCO3, which can improve the reversible specific capacity of the electrode by forming a C-O-K compound with potassium. Thanks to the coupling effect of the hierarchical porous structure with an orderly tube array and rich CO functional groups, the obtained porous carbon materials exhibited excellent kinetics and impressive rate capability as the anode of potassium-ion batteries (PIBs) with high capacities of 209 mA h g-1 at 10 A g-1 and 156 mA h g-1 at 30 A g-1. This work not only provides a facile, green, sustainable approach to fabricating novel carbon materials, but also demonstrates the promising prospect of oriented porous carbon in exploring advanced electrode materials for PIBs.

9.
Heliyon ; 10(3): e24199, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38317969

RESUMO

The vast majority of volatile organic compounds (VOCs) are of biological origin and do not affect human health, while some VOCs or their oxidation products can damage the respiratory system, nervous system, digestive system and blood system after long-term inhalation by humans. There is limited evidence regarding the association of VOCs exposure with childhood asthma. In this study, we examined the associations between metabolites of VOCs (mVOCs) in urine and childhood asthma. We included a total of 1542 children aged 3-12 years who had information on urinary mVOCs, asthma and essential covariates in the current analyses. After controlling for covariates, we used logistic regression to assess the association between urinary mVOCs and childhood asthma. Then, we examined effect measure modification by child age, gender, race/ethnicity and serum cotinine. 2-Methylhippuric acid (xylene metabolites) (OR: 1.14; 95 % CI: 0.87, 1.59), N-acetyl-S-(benzyl)-l-cysteine (toluene metabolites) (OR: 1.15 95 % CI: 0.76, 1.71), N-acetyl-S-(2-carboxyethyl)-l-cysteine (acrolein metabolites) (OR: 1.09; 95 % CI: 0.61, 1.75), N-acetyl-S-(3-hydroxypropyl)-l-cysteine (acrolein metabolites) (OR: 1.10; 95 % CI: 0.66, 1.80), and N-acetyl-S-(3-hydroxypropyl-1-methyl)-l-cysteine (crotonaldehyde metabolites) (OR: 1.18; 95 % CI: 0.68, 2.01) were weakly associated with the prevalence of asthma in children. Among female children, 2MHA (2-methylhippuric acid) in urine was significantly associated with the prevalence of asthma (OR: 1.81 95 % CI: 1.07, 3.05). At the same time, BMA (N-acetyl-S-(benzyl)-l-cysteine) was significantly associated with the prevalence of asthma in non-Hispanic White (OR:2.09 95 % CI: 0.91, 4.66) and Black (OR:1.90 95 % CI: 0.96, 3.71) children. We found that gender modified the associations between urinary 2MHA and the odds of asthma (interaction term p value = 0.03). Therefore, exposure to VOCs and the development of childhood asthma remains controversial, and the interpretation of these results needs to be treated with caution and should be confirmed in future studies.Therefore, exposure to VOCs and the development of childhood asthma remains controversial, and the interpretation of these results needs to be treated with caution and should be confirmed in future studies.

10.
Oncology ; 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38320546

RESUMO

Introduction Recurrence after microwave ablation (MWA) has not been extensively studied. We aimed to investigate the patterns, treatments, and survival of patients with hepatocellular carcinoma (HCC) who experienced early and late recurrence after MWA. Methods This retrospective study included patients with HCC recurrence after MWA as the initial treatment from January 2008 to December 2021. Recurrence patterns, treatments, and outcomes between patients with early and late HCC recurrence were compared. Prognostic factors of post-recurrence survival (PRS) were identified by multivariable Cox regression analyses. Results Among 222 patients, 128 developed early recurrence (≤2 years after MWA) and 94 had late recurrence (>2 years). Majority of the recurrent HCC were intrahepatic-only recurrence, within the Milan criteria, and received potentially curative treatment. No significant differences in the recurrence patterns, vascular invasion, tumor staging, post-recurrence treatments or median PRS (35.0 vs 33.0 months, p=0.523) were identified between patients with early and late recurrence. Multivariable analyses suggested that multiple tumor number (hazard ratio (HR), 1.54; 95% CI: 1.03-2.30, p=0.038), extra-hepatic recurrence (HR, 2.14, 95% CI: 1.16-3.92, p=0.015), vascular invasion (HR, 2.37, 95% CI: 1.18-4.76, p=0.038) and higher ALBI grade (HR, 2.18, 95% CI: 1.54-3.08, p<0.001) were independent risk factors of worse PRS, while curative treatment after recurrence (HR, 0.59, 95% CI: 0.38-0.92, p=0.038) was associated with better PRS. Conclusions No differences in recurrence patterns, post-recurrent treatments or PRS were found between HCC patients with early and late recurrence following MWA. Tumor burden and patients' liver function reserve should be considered to decide the optimal post-recurrence treatment after MWA.

11.
Sci Rep ; 14(1): 2775, 2024 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-38307987

RESUMO

We explored the joint effects of different metabolic obesity phenotypes on all-cause and disease-specific mortality risk among the American population. Data were obtained from the National Health and Nutrition Examination Survey (NHANES) 1999-2018. Mortality outcome data were from mortality files linked to National Death Index record and follow-up information was up to December 31, 2019. 50,013 participants were finally included. Four metabolic obesity phenotypes were defined based on obesity and metabolic status: metabolically healthy obese (MHO), metabolically unhealthy obese (MUO), metabolically healthy non-obese (MHNO), and metabolically unhealthy non-obese (MUNO). Population-weighted Cox proportional hazards models were used to explore the all-cause and disease-specific mortality risk of metabolic obesity phenotypes. The all-cause mortality risk of MUO and MUNO was significantly higher than MHNO. MUNO was associated with a significantly increased risk of death from heart disease (HR: 1.40, 95% CI 1.16-1.70), hypertension (HR: 1.68, 95% CI 1.34-2.12), diabetes (HR: 2.29, 95% CI 1.67-3.15), and malignant neoplasms (HR:1.29, 95% CI 1.09-1.53). Metabolic unhealth significantly increased the risk of all-cause mortality, regardless of obesity status. Among individuals with metabolic unhealthy status, obesity significantly reduced the risk of all-cause mortality (HR: 0.91, 95% CI 0.85-0.98). Our study highlights the importance of identifying and characterizing metabolic obesity phenotypes in obese and metabolically abnormal patients, as well as healthy adults. Comprehensive evaluation of obesity and metabolic status is necessary to adopt appropriate interventions and treatment measures and maximize patient benefit.


Assuntos
Síndrome Metabólica , Obesidade , Adulto , Humanos , Estados Unidos/epidemiologia , Fatores de Risco , Inquéritos Nutricionais , Índice de Massa Corporal , Estudos Longitudinais , Obesidade/complicações , Síndrome Metabólica/epidemiologia , Fenótipo
12.
World J Gastroenterol ; 30(2): 170-183, 2024 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-38312122

RESUMO

BACKGROUND: Deep learning provides an efficient automatic image recognition method for small bowel (SB) capsule endoscopy (CE) that can assist physicians in diagnosis. However, the existing deep learning models present some unresolved challenges. AIM: To propose a novel and effective classification and detection model to automatically identify various SB lesions and their bleeding risks, and label the lesions accurately so as to enhance the diagnostic efficiency of physicians and the ability to identify high-risk bleeding groups. METHODS: The proposed model represents a two-stage method that combined image classification with object detection. First, we utilized the improved ResNet-50 classification model to classify endoscopic images into SB lesion images, normal SB mucosa images, and invalid images. Then, the improved YOLO-V5 detection model was utilized to detect the type of lesion and its risk of bleeding, and the location of the lesion was marked. We constructed training and testing sets and compared model-assisted reading with physician reading. RESULTS: The accuracy of the model constructed in this study reached 98.96%, which was higher than the accuracy of other systems using only a single module. The sensitivity, specificity, and accuracy of the model-assisted reading detection of all images were 99.17%, 99.92%, and 99.86%, which were significantly higher than those of the endoscopists' diagnoses. The image processing time of the model was 48 ms/image, and the image processing time of the physicians was 0.40 ± 0.24 s/image (P < 0.001). CONCLUSION: The deep learning model of image classification combined with object detection exhibits a satisfactory diagnostic effect on a variety of SB lesions and their bleeding risks in CE images, which enhances the diagnostic efficiency of physicians and improves the ability of physicians to identify high-risk bleeding groups.


Assuntos
Aprendizado Profundo , Humanos , Intestino Delgado/diagnóstico por imagem , Intestino Delgado/patologia
13.
Int. microbiol ; 27(1): 127-142, Feb. 2024. graf
Artigo em Inglês | IBECS | ID: ibc-230249

RESUMO

Digestive and respiratory tracts are inhabited by rich bacterial communities that can vary between their different segments. In comparison with other bird taxa with developed caeca, parrots that lack caeca have relatively lower variability in intestinal morphology. Here, based on 16S rRNA metabarcoding, we describe variation in microbiota across different parts of parrot digestive and respiratory tracts both at interspecies and intraspecies levels. In domesticated budgerigar (Melopsittacus undulatus), we describe the bacterial variation across eight selected sections of respiratory and digestive tracts, and three non-destructively collected sample types (faeces, and cloacal and oral swabs). Our results show important microbiota divergence between the upper and lower digestive tract, but similarities between respiratory tract and crop, and also between different intestinal segments. Faecal samples appear to provide a better proxy for intestinal microbiota composition than the cloacal swabs. Oral swabs had a similar bacterial composition as the crop and trachea. For a subset of tissues, we confirmed the same pattern also in six different parrot species. Finally, using the faeces and oral swabs in budgerigars, we revealed high oral, but low faecal microbiota stability during a 3-week period mimicking pre-experiment acclimation. Our findings provide a basis essential for microbiota-related experimental planning and result generalisation in non-poultry birds.(AU)


Assuntos
Humanos , Animais , Papagaios/metabolismo , Trato Gastrointestinal/microbiologia , Microbiota , Bactérias/genética , RNA Ribossômico 16S/genética , Sistema Respiratório/microbiologia , Trato Gastrointestinal/metabolismo , Microbiologia , Técnicas Microbiológicas , Microbiota/genética , Periquitos
14.
Hortic Res ; 11(2): uhad272, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38333730

RESUMO

Resistant crop cultivars can recruit beneficial rhizobacteria to resist disease. However, whether this recruitment is regulated by quantitative trait loci (QTL) is unclear. The role of QTL in recruiting specific bacteria against bacterial wilt (BW) is an important question of practical significance to disease management. Here, to identify QTL controlling BW resistance, Super-BSA was performed in F2 plants derived from resistant eggplant cultivar R06112 × susceptible cultivar S55193. The QTL was narrowed down through BC1F1-BC3F1 individuals by wilting symptoms and KASP markers. Rhizosphere bacterial composition of R06112, S55193, and resistant individuals EB158 (with the QTL) and susceptible individuals EB327 (without QTL) from BC2F1 generation were assessed by Illumina sequencing-based analysis, and the activation of plant immunity by the bacterial isolates was analyzed. Evidence showed that BW-resistant is controlled by one QTL located at the 270 kb region on chromosome 10, namely EBWR10, and nsLTPs as candidate genes confirmed by RNA-Seq. EBWR10 has a significant effect on rhizobacteria composition and significantly recruits Bacillus. pp. A SynCom of three isolated Bacillus. pp trains significantly reduced the disease incidence, changed activities of CAT, PPO, and PAL and concentration of NO, H2O2, and O2-, activated SA and JA signaling-dependent ISR, and displayed immune activation against Ralstonia solanacearum in eggplant. Our findings demonstrate for the first time that the QTL can recruit beneficial rhizobacteria, which jointly promote the suppression of BW. This method charts a path to develop the QTL in resistant cultivar-driven probiotics to ameliorate plant diseases.

15.
Cancer Res ; 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38335272

RESUMO

Reprogramming of energy metabolism exerts pivotal functions in cancer progression and immune surveillance. Identification of the mechanisms mediating metabolic changes in cancer may lead to improved strategies to suppress tumor growth and stimulate anti-tumor immunity. Here, it was observed that the secretomes of hypoxic breast cancer cells and breast cancer stem cells (BCSCs) induced reprogramming of metabolic pathways, particularly glycolysis, in normoxic breast cancer cells. Screening of the BCSC secretome identified MIF as a pivotal factor potentiating glycolysis. Mechanistically, MIF increased c-MYC-mediated transcriptional upregulation of the glycolytic enzyme aldolase C by activating WNT/ß-CATENIN signaling. Targeting MIF attenuated glycolysis and impaired xenograft growth and metastasis. MIF depletion in breast cancer cells also augmented intratumoral cytolytic CD8+ T cells and pro-inflammatory macrophages while decreasing Tregs and tumor-associated neutrophils in the tumor microenvironment. Consequently, targeting MIF improved the therapeutic efficacy of immune checkpoint blockade (ICB) in triple-negative breast cancer. Collectively, this study proposes MIF as an attractive therapeutic target to circumvent metabolic reprogramming and immunosuppression in breast cancer.

16.
Foods ; 13(4)2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38397503

RESUMO

The escalating demand for processed foods has led to the widespread industrial use of glucose isomerase (GI) for high-fructose corn syrup (HFCS) production. This reliance on GIs necessitates continual Co2+ supplementation to sustain high catalytic activity across multiple reaction cycles. In this study, Serratia marcescens GI (SmGI) was immobilized onto surfaces of the metal-organic framework (MOF) material MOF (Co)-525 to generate MOF (Co)-525-GI for use in catalyzing glucose isomerization to generate fructose. Examination of MOF (Co)-525-GI structural features using scanning electron microscopy-energy dispersive spectroscopy, Fourier-transform infrared spectroscopy, and ultraviolet spectroscopy revealed no structural changes after SmGI immobilization and the addition of Co2+. Notably, MOF (Co)-525-GI exhibited optimal catalytic activity at pH 7.5 and 70 °C, with a maximum reaction rate (Vmax) of 37.24 ± 1.91 µM/min and Km value of 46.25 ± 3.03 mM observed. Remarkably, immobilized SmGI exhibited sustained high catalytic activity over multiple cycles without continuous Co2+ infusion, retaining its molecular structure and 96.38% of its initial activity after six reaction cycles. These results underscore the potential of MOF (Co)-525-GI to serve as a safer and more efficient immobilized enzyme technology compared to traditional GI-based food-processing technologies.

17.
Artigo em Inglês | MEDLINE | ID: mdl-38329851

RESUMO

Distribution comparison plays a central role in many machine learning tasks like data classification and generative modeling. In this study, we propose a novel metric, called Hilbert curve projection (HCP) distance, to measure the distance between two probability distributions with low complexity. In particular, we first project two high-dimensional probability distributions using Hilbert curve to obtain a coupling between them, and then calculate the transport distance between these two distributions in the original space, according to the coupling. We show that HCP distance is a proper metric and is well-defined for probability measures with bounded supports. Furthermore, we demonstrate that the modified empirical HCP distance with the Lp cost in the d-dimensional space converges to its population counterpart at a rate of no more than O(n-1/2max{d,p}). To suppress the curse-of-dimensionality, we also develop two variants of the HCP distance using (learnable) subspace projections. Experiments on both synthetic and real-world data show that our HCP distance works as an effective surrogate of the Wasserstein distance with low complexity and overcomes the drawbacks of the sliced Wasserstein distance. The code of this work is at https://github.com/sherlockLitao/HCP.

18.
Pharmaceuticals (Basel) ; 17(2)2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38399384

RESUMO

Bone tuberculosis, an extrapulmonary manifestation of tuberculosis, presents unique treatment challenges, including its insidious onset and complex pathology. While advancements in anti-tubercular therapy have been made, the efficacy is often limited by difficulties in achieving targeted drug concentrations and avoiding systemic toxicity. The intricate bone structure and presence of granulomas further impede effective drug delivery. Nano-drug delivery systems have emerged as a promising alternative, offering the enhanced targeting of anti-tubercular drugs. These systems, characterized by their minute size and adaptable surface properties, can be tailored to improve drug solubility, stability, and bioavailability, while also responding to specific stimuli within the bone TB microenvironment for controlled drug release. Nano-drug delivery systems can encapsulate drugs for precise delivery to the infection site. A significant innovation is their integration with prosthetics or biomaterials, which aids in both drug delivery and bone reconstruction, addressing the infection and its osteological consequences. This review provides a comprehensive overview of the pathophysiology of bone tuberculosis and its current treatments, emphasizing their limitations. It then delves into the advancements in nano-drug delivery systems, discussing their design, functionality, and role in bone TB therapy. The review assesses their potential in preclinical research, particularly in targeted drug delivery, treatment efficacy, and a reduction of side effects. Finally, it highlights the transformative promise of nanotechnology in bone TB treatments and suggests future research directions in this evolving field.

19.
Vaccines (Basel) ; 12(2)2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38400158

RESUMO

The Omicron EG.5 lineage of SARS-CoV-2 is currently on a trajectory to become the dominant strain. This phase 2 study aims to evaluate the immunogenicity of SCTV01E-2, a tetravalent protein vaccine, with a specific emphasis on its immunogenicity against Omicron EG.5, comparing it with its progenitor vaccine, SCTV01E (NCT05933512). As of 12 September 2023, 429 participants aged ≥18 years were randomized into the groups SCTV01E (N = 215) and SCTV01E-2 (N = 214). Both vaccines showed increases in neutralizing antibody (nAb) against Omicron EG.5, with a 5.7-fold increase and a 9.0-fold increase in the SCTV01E and SCTV01E-2 groups 14 days post-vaccination, respectively. The predetermined statistical endpoints were achieved, showing that the geometric mean titer (GMT) of nAb and the seroresponse rate (SRR) against Omicron EG.5 were significantly higher in the SCTV01E-2 group than in the SCTV01E group. Additionally, SCTV01E and SCTV01E-2 induced a 5.5-fold and a 5.9-fold increase in nAb against XBB.1, respectively. Reactogenicity was generally mild and transient. No vaccine-related serious adverse events (SAEs), adverse events of special interest (AESIs), or deaths were reported. In summary, SCTV01E-2 elicited robust neutralizing responses against Omicron EG.5 and XBB.1 without raising safety concerns, highlighting its potential as a versatile COVID-19 vaccine against SARS-CoV-2 variants.

20.
Cancer Med ; 13(3): e7024, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38400661

RESUMO

OBJECTIVES: The use of immune checkpoint inhibitors, particularly PD-1 inhibitors, has revolutionized the treatment of advanced tumors and shown significant improvements in patient survival rates. However, which PD-1 inhibitor is more effective and safer for a specific indication remains unclear. To address this problem, our study aimed to evaluate the effectiveness and safety of different PD-1 inhibitors in combination with chemotherapy as first-line therapy for individuals with advanced non-small-cell lung cancer (NSCLC) without driver genes in the real world. MATERIALS AND METHODS: We conducted a retrospective study of individuals diagnosed with aNSCLC who received immune checkpoint inhibitors (ICIs) with modified PD-1 inhibitors, including Sintilimab, Toripalimab, Tislelizumab, Camrelizumab, or Pembrolizumab as first-line treatment between March 5th, 2016 and October 20th, 2022. We assessed demographic and clinical information and analyzed clinical response, survival outcomes, and safety profiles. The primary endpoint was overall survival (OS), and the secondary endpoints included progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and safety. RESULTS: As of the date cut-off on October 20th, 2022, the median follow-up time was 20.62 months. A total of 204 patients were enrolled in the study, including 56 (27.5%) patients receiving modified PD-1 inhibitors (Sintilimab, Toripalimab, Tislelizumab, or Camrelizumab) in combination with chemotherapy and 148 (72.5%) patients receiving Pembrolizumab in combination with chemotherapy. In the overall cohort, the median overall survival (OS) was 26.9 months (95%CI, 22.3-31.6), the median progression-free survival (PFS) was 8.4 months (95%CI, 6.9-9.8), and the objective response rate (ORR) and disease control rate (DCR) were 47.6% (95%CI, 29.9-43.6) and 84.3% (95%CI, 78.4-88.9). The mOS of modified PD-1 inhibitors group and Pembrolizumab group were 30.7 (95%CI, 17.3-44.4) months and 26.8 (95%CI, 22.2-31.4) months. The mPFS of two groups were 8.3(95%CI, 6.9-9.6) months and 8.8 (95%CI, 6.9-10.7) months, respectively. There was no statistical difference between the two groups in terms of OS or PFS. The ORR for the two groups was 48.2% (95%CI, 34.8-61.8) and 47.3% (95%CI, 39.1-5.6), respectively. However, due to the limited sample size, the difference was not statistically significant. On the other hand, the DCR tended to be higher in the Pembrolizumab group (86.5%; 95%CI, 79.7-91.4) compared to the modified PD-1 inhibitors group (78.6%; 95%CI, 65.2-87.9), and this difference was statistically significant (p = 0.006). In terms of safety, both groups exhibited favorable clinical safety profiles. The only two types of potentially immune-related adverse events reported were pneumonitis and reactive cutaneous capillary endothelial proliferation (RCCEP). CONCLUSIONS: The modified PD-1 inhibitors showed comparable survival outcomes and manageable safety profiles in NSCLC compared to Pembrolizumab. Moreover, these inhibitors exhibited improved accessibility and economic outcomes compared to Pembrolizumab. While there were similarities in drug-related and immunotherapy-related adverse reactions between the modified PD-1 inhibitors and Pembrolizumab, there were some slight differences. Further prospective and retrospective studies would be necessary to validate these findings beyond the scope of the CTONG1901 study.

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