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1.
Huan Jing Ke Xue ; 45(5): 2871-2880, 2024 May 08.
Artigo em Chinês | MEDLINE | ID: mdl-38629549

RESUMO

Presently, the improvement of soil organic matter is the basis to ensure food security, but the accumulation and transformation characteristics of soil phosphorus (P) as affected by organic matter remain unclear. The accumulation, transformation, and migration characteristics of soil P in different soil layers of vegetable fields were researched under the application of organic materials. Six treatments were set up in the experiment:control (no fertilization), traditional fertilizer application by farmers, biochar, chicken manure, food waste, and straw application. Available phosphorus (Olsen-P), water-soluble phosphorus (CaCl2-P) content, soil phosphorus forms, soil organic matter (SOM), and pH were determined during the pepper harvest period. In the 0-5 cm and 5-10 cm soil layers, the available phosphorus content of traditional fertilization of farmers was higher, and the available phosphorus content of the four organic materials was in the order of straw > biochar > chicken manure > food waste. Compared to that with food waste, the straw and biochar treatments increased soil available phosphorus by 59.6%-67.3% and 29.1%-36.9%, respectively. The straw treatment could easily enhance the soil labile P pool, and soil labile P in the 0-5 cm soil layer increased by 47.3% and 35.1% compared with that under the chicken manure and food waste treatments, respectively. With the increase in soil depth, the proportion of available phosphorus in the chicken manure treatment decreased the least, and available phosphorus of the 20-30 cm soil layer accounted for 55.9% of the topsoil layer but only accounted for 16.0%-34.0% under treatment with the other three materials. Compared with that under the traditional fertilization of farmers, the pH significantly increased by 0.18-0.36 units after the application of organic fertilizer, and the pH of the chicken manure and food waste treatments was significantly higher than that of biochar and straw (P < 0.05). SOM content under the biochar treatment significantly increased by 7.7%-17.6% compared to that under the other three organic materials. Among the four organic materials, the straw treatment boosted the labile P pool the most, which was conducive to the rapid increase in plant-available P. Phosphorus was most likely to migrate downward under the chicken manure treatment. In the field management based on soil fertility enhancement, the application of biochar could not only improve soil pH and SOM but also avoid excessive accumulation of phosphorus in the surface layer, which decreases environmental risks.


Assuntos
Agricultura , Carvão Vegetal , Eliminação de Resíduos , Animais , Fósforo , Verduras , Fertilizantes , Esterco , Solo/química , Galinhas
2.
Joint Bone Spine ; 91(4): 105728, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38580102

RESUMO

OBJECTIVE: Systemic Lupus Erythematosus (SLE) is an autoimmune disease that occurs at higher rates in young women. Evidence suggests that SLE may be associated with ovarian dysfunction. Therefore, it is crucial to investigate the possible effects of SLE on ovarian reserve function. METHODS: PubMed, Embase, Web of Science, Scopus, Cochrane Library, and ClinicalTrials.gov databases were searched from inception to July 2023 to identify studies that compared ovarian reserve in patients with SLE to that of healthy individuals. The study examined anti-müllerian hormone (AMH), antral follicle count (AFC), and follicle-stimulating hormone (FSH) as outcomes. RESULTS: Thirteen studies (n=1017) were eligible for meta-analysis. Females with SLE had significantly lower levels of AMH (weighted mean difference [WMD]: -1.07, 95% confidence interval [CI]: -1.37 to -0.76, P<0.001) and AFC (WMD: -3.46, 95% CI: -4.57 to -2.34, P<0.001). There was no significant difference in FSH levels. Subgroup analyses by age of onset revealed that SLE patients with adult-onset had significantly lower AMH levels (WMD: -1.44, 95% CI: -1.71 to -1.18, P<0.001), lower AFCs (WMD: -3.11, 95% CI: -3.60 to -2.61, P<0.001) and higher FSH levels (WMD: 0.60, 95% CI: 0.15 to 1.05, P<0.01). However, SLE patients with juvenile-onset did not exhibit significant differences in their AMH and FSH levels, except for AFCs (WMD: -7.27, 95% CI: -12.39 to -2.14, P<0.01). CONCLUSION: The impact of SLE on ovarian reserve is significant, and the effect may be particularly severe in cases of adult-onset SLE.

3.
Risk Anal ; 2024 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-38616513

RESUMO

Hemodialysis is an important part of nosocomial infection prevention and control (IPC). This study aimed to identify the key potential risk areas and failure modes in hemodialysis rooms in hospitals and put forward a series of improvement measures to prevent and control the spread of the coronavirus disease 2019 (COVID-19). Hemodialysis patients are highly susceptible to COVID-19 and usually have a high incidence of severe illness and mortality after infection with COVID-19. Therefore, IPC in hemodialysis patients is of crucial strategic significance. Based on 30 domain experts' interviews and careful analysis of prevention and control documents, we constructed a comprehensive failure system for a model that identifies the potential risks for nosocomial COVID-19 infection in the hemodialysis room. Subsequently, a thorough risk assessment of the potential failure factors identified in our model was conducted. The failure key factors corresponding to the human element in medical waste (garbage) disposal (C2) are verified to be the highest risk factors. They are as follows: The cleaning staff did not dispose of different types of medical waste (garbage) (C21), did not wear masks according to the regulations (C22), and lacked knowledge and norms of nosocomial IPC (C23). This study provides valuable insights for hospital decision-makers on the potential failure factors related to COVID-19 infections in hemodialysis rooms. By working with hospital infection specialists, the suggested improvement measures can help reduce the risk of virus exposure among hospital medical staff, patients, and cleaning staff.

4.
Zhongguo Zhong Yao Za Zhi ; 49(4): 912-923, 2024 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-38621898

RESUMO

With the promotion of chemical fertilizer and pesticide reduction and green production of traditional Chinese medicines, microbial fertilizers have become a hot way to achieve the zero-growth of chemical fertilizers and pesticides, improve the yield and qua-lity of medicinal plants, maintain soil health, and promote the sustainable development of the planting industry of Chinese herbal medicines. Soil conditions and microenvironments are crucial to the growth, development, and quality formation of medicinal plants. Microbial fertilizers, as environmentally friendly fertilizers acting on the soil, can improve soil quality by replenishing organic matter and promoting the metabolism of beneficial microorganisms to improve the yield and quality of medicinal plants. In this regard, understanding the mechanism of microbial fertilizer in regulating the quality formation of medicinal plants is crucial for the development of herbal eco-agriculture. This study introduces the processes of microbial fertilizers in improving soil properties, participating in soil nutrient cycling, enhancing the resistance of medicinal plants, and promoting the accumulation of medicinal components to summarize the mechanisms and roles of bacterial fertilizers in regulating the quality formation of medicinal plants. Furthermore, this paper introduces the application of bacterial fertilizers in medicinal plants and makes an outlook on their development, with a view to providing a scientific basis for using microbial fertilizers to improve the quality of Chinese herbal medicines, improve the soil environment, promote the sustainable development of eco-agriculture of traditional Chinese medicine, and popularize the application of microbial fertilizers.


Assuntos
Praguicidas , Plantas Medicinais , Fertilizantes , Agricultura , Solo/química , Bactérias/genética , Extratos Vegetais , Microbiologia do Solo
5.
Microb Cell Fact ; 23(1): 100, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38566071

RESUMO

Surfactin is a cyclic hexalipopeptide compound, nonribosomal synthesized by representatives of the Bacillus subtilis species complex which includes B. subtilis group and its closely related species, such as B. subtilis subsp subtilis, B. subtilis subsp spizizenii, B. subtilis subsp inaquosorum, B. atrophaeus, B. amyloliquefaciens, B. velezensis (Steinke mSystems 6: e00057, 2021) It functions as a biosurfactant and signaling molecule and has antibacterial, antiviral, antitumor, and plant disease resistance properties. The Bacillus lipopeptides play an important role in agriculture, oil recovery, cosmetics, food processing and pharmaceuticals, but the natural yield of surfactin synthesized by Bacillus is low. This paper reviews the regulatory pathways and mechanisms that affect surfactin synthesis and release, highlighting the regulatory genes involved in the transcription of the srfAA-AD operon. The several ways to enhance surfactin production, such as governing expression of the genes involved in synthesis and regulation of surfactin synthesis and transport, removal of competitive pathways, optimization of media, and fermentation conditions were commented. This review will provide a theoretical platform for the systematic genetic modification of high-yielding strains of surfactin.


Assuntos
Bacillus , Bacillus/genética , Bacillus/metabolismo , Bacillus subtilis/genética , Bacillus subtilis/metabolismo , Óperon , Fermentação , Lipopeptídeos , Peptídeos Cíclicos
6.
Clin Otolaryngol ; 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38558499

RESUMO

BACKGROUND: Laryngeal leukoplakia (LL) is a white lesion with high potential of recurrence and malignant transformation. Currently, CO2 laser has become the primary surgical treatment for LL, and the recurrence and malignant transformation rates after treatment vary widely. OBJECTIVE: We performed a systematic review and meta-analysis dedicated to evaluating the rates of recurrence and malignant transformation of LL lesions treated with CO2 laser and exploring relevant risk factors for recurrence or malignant transformation. METHODS: Literature searches were conducted on ProQuest, PubMed, Web of Science, Ovid Medline, Embase, and Cochrane databases. Some articles identified through hand searching were included. RESULTS: A total of 14 articles and 1462 patients were included in this review. Pooled results showed that the overall recurrence rate was 15%, and the malignant transformation rate was 3%. Subgroup analysis showed that the dysplasia grade was not a significant risk factor for the recurrence and malignant transformation of LL (P > .05). CONCLUSIONS: The results of this systematic review and meta-analysis suggest that the CO2 laser is a safe and effective surgical instrument for the excision of LL, which yields low rates of recurrence and malignant transformation. The risk factors relevant to recurrence or malignant transformation remain unclear and require further investigation.

7.
PNAS Nexus ; 3(4): pgae118, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38595803

RESUMO

Enzymatic humification plays a crucial biogeochemical role in eliminating steroidal estrogens and expanding organic carbon stocks. Estrogenic contaminants in agroecosystems can be taken up and acropetally translocated by crops, but the roles of laccase-triggered rhizospheric humification (L-TRH) in pollutant dissipation and plant uptake remain poorly understood. In this study, the laccase-induced decontamination and humification mechanisms of 17ß-estradiol (E2) in water-crop media were investigated by performing greenhouse pot experiments with maize seedlings (Zea mays L.). The results demonstrated that L-TRH effectively dissipated E2 in the rhizosphere solution and achieved the kinetic constants of E2 dissipation at 10 and 50 µM by 8.05 and 2.75 times as much as the treatments without laccase addition, respectively. The copolymerization of E2 and root exudates (i.e. phenols and amino acids) consolidated by L-TRH produced a larger amount of humified precipitates with the richly functional carbon architectures. The growth parameters and photosynthetic pigment levels of maize seedlings were greatly impeded after a 120-h exposure to 50 µM E2, but L-TRH motivated the detoxication process and thus mitigated the phytotoxicity and bioavailability of E2. The tested E2 contents in the maize tissues initially increased sharply with the cultivation time but decreased steadily. Compared with the treatment without laccase addition, the uptake and accumulation of E2 in the maize tissues were obviously diminished by L-TRH. E2 oligomers such as dimer, trimer, and tetramer recognized in the rhizosphere solution were also detected in the root tissues but not in the shoots, demonstrating that the acropetal translocation of E2 oligomers was interrupted. These results highlight a promising strategy for decontaminating estrogenic pollutants, boosting rhizospheric humification, and realizing low-carbon emissions, which would be beneficial for agroenvironmental bioremediation and sustainability.

8.
Front Oncol ; 14: 1342998, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38577341

RESUMO

Background: DNMT3A mutations can be detected in premalignant hematopoietic stem cells and are primarily associated with clonal hematopoiesis of indeterminate potential; however, current evidence does not support assigning them to a distinct European Leukemia Net (ELN) prognostic risk stratification. CD7 is a lymphoid antigen expressed on blasts in approximately 30% of acute myeloid leukemia (AML), and its role in AML remains unclear and depends on subgroup evaluation. This study investigated the prognostic value of DNMT3A mutation combined with CD7 expression in AML. Methods: We retrospectively analyzed the clinical data of 297 newly diagnosed non-M3 AML patients. According to the DNMT3A mutation and CD7 expression in AML cells, patients were divided into the DNMT3A-mutated/CD7-positive (CD7+), DNMT3A-mutated/CD7-negative (CD7-), DNMT3A-wild-type/CD7+, and DNMT3A-wild-type/CD7- groups. Results: The DNMT3A-mutated/CD7+ group had lower complete remission rates and higher relapse rates. Importantly, these patients had significantly shorter overall survival (OS) and relapse-free survival (RFS). Furthermore, multivariate analysis showed that CD7+ with DNMT3A mutation was an independent risk factor for OS and RFS. Conclusion: CD7+ with DNMT3A mutation predicts a poor prognosis in AML patients, and the immunophenotype combined with molecular genetic markers can help to further refine the current risk stratification of AML.

9.
Cell Death Dis ; 15(4): 248, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38575587

RESUMO

Gastric cancer (GC) contains subpopulations of cancer stem cells (CSCs), which are described as the main contributors in tumor initiation and metastasis. It is necessary to clarify the molecular mechanism underlying CSCs phenotype and develop novel biomarkers and therapeutic targets for gastric cancer. Here, we show that POLQ positively regulates stem cell-like characteristics of gastric cancer cells, knockdown of POLQ suppressed the stemness of GC cells in vitro and in vivo. Further mechanistic studies revealed that POLQ knockdown could downregulate the expression of dihydroorotate dehydrogenase (DHODH). DHODH overexpression rescued the reduced stemness resulted by POLQ knockdown. Furthermore, we found that POLQ expression correlated with resistance to ferroptosis, and POLQ inhibition renders gastric cancer cells more vulnerable to ferroptosis. Further investigation revealed that POLQ regulated DHODH expression via the transcription factors E2F4, thereby regulating ferroptosis resistance and stemness of gastric cancer cells. Given the importance of POLQ in stemness and ferroptosis resistance of GC, we further evaluated the therapeutic potential of POLQ inhibitor novobiocin, the results show that novobiocin attenuates the stemness of GC cells and increased ferroptosis sensitivity. Moreover, the combination of POLQ inhibitor and ferroptosis inducer synergistically suppressed MGC-803 xenograft tumor growth and diminished metastasis. Our results identify a POLQ-mediated stemness and ferroptosis defense mechanism and provide a new therapeutic strategy for gastric cancer.


Assuntos
Ferroptose , Neoplasias Gástricas , Humanos , Linhagem Celular Tumoral , Di-Hidro-Orotato Desidrogenase , Regulação para Baixo/genética , Ferroptose/genética , Novobiocina , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética
10.
Front Physiol ; 15: 1358850, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38601214

RESUMO

The human epidermal growth factor receptor (HER) family consists of four members, activated by two families of ligands. They are known for mediating cell-cell interactions in organogenesis, and their deregulation has been associated with various cancers, including breast and esophageal cancers. In particular, aberrant epidermal growth factor receptor (EGFR) and HER2 signaling drive disease progression and result in poorer patient outcomes. Nitric oxide (NO) has been proposed as an alternative activator of the HER family and may play a role in this aberrant activation due to its ability to induce s-nitrosation and phosphorylation of the EGFR. This review discusses the potential impact of NO on HER family activation and downstream signaling, along with its role in the efficacy of therapeutics targeting the family.

11.
Mol Biol Rep ; 51(1): 507, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622406

RESUMO

BACKGROUND: Our previous research has demonstrated that hypoxic preconditioning (HPC) can improve spatial learning and memory abilities in adult mice. Adult hippocampal neurogenesis has been associated with learning and memory. The Neurogenic locus notch homolog protein (Notch) was involved in adult hippocampal neurogenesis, as well as in learning and memory. It is currently unclear whether the Notch pathway regulates hippocampal neuroregeneration by modifying the DNA methylation status of the Notch gene following HPC. METHOD: The HPC animal model and cell model were established through repeated hypoxia exposure using mice and the mouse hippocampal neuronal cell line HT22. Step-down test was conducted on HPC mice. Real-time PCR and Western blot analysis were used to assess the mRNA and protein expression levels of Notch1 and hairy and enhancer of split1 (HES1). The presence of BrdU-positive cells and Notch1 expression in the hippocampal dental gyrus (DG) were examined with confocal microscopy. The methylation status of the Notch1 was analyzed using methylation-specific PCR (MS-PCR). HT22 cells were employed to elucidate the impact of HPC on Notch1 in vitro. RESULTS: HPC significantly improved the step-down test performance of mice with elevated levels of mRNA and protein expression of Notch1 and HES1 (P < 0.05). The intensities of the Notch1 signal in the control group, the H group and the HPC group were 2.62 ± 0.57 × 107, 2.87 ± 0.84 × 107, and 3.32 ± 0.14 × 107, respectively, and the number of BrdU (+) cells in the hippocampal DG were 1.83 ± 0.54, 3.71 ± 0.64, and 7.29 ± 0.68 respectively. Compared with that in C and H group, the intensity of the Notch1 signal and the number of BrdU (+) cells increased significantly in HPC group (P < 0.05). The methylation levels of the Notch1 promoter 0.82 ± 0.03, 0.65 ± 0.03, and 0.60 ± 0.02 in the C, H, and HPC groups, respectively. The methylation levels of Notch1 decreased significantly (P < 0.05). The effect of HPC on HT22 cells exhibited similarities to that observed in the hippocampus. CONCLUSION: HPC may confer neuroprotection by activating the Notch1 signaling pathway and regulating its methylation level, resulting in the regeneration of hippocampal neurons.


Assuntos
Metilação de DNA , Hipocampo , Camundongos , Animais , Metilação de DNA/genética , Bromodesoxiuridina/metabolismo , Hipocampo/metabolismo , Hipóxia/genética , Hipóxia/metabolismo , Receptores Notch/metabolismo , RNA Mensageiro/metabolismo , Receptor Notch1/genética , Receptor Notch1/metabolismo
12.
Pediatr Blood Cancer ; : e31014, 2024 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-38644612

RESUMO

BACKGROUND: The outcome of extramedullary infiltration (EMI) in pediatric acute myeloid leukemia (AML) is controversial, and little is known about the implications of stem cell transplantation (SCT) and gemtuzumab ozogamicin (GO) treatment on patients with EMI. METHODS: We retrieved the clinical data of 713 pediatric patients with AML from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) dataset, and analyzed the clinical and prognostic characteristics of patients with EMI at diagnosis and relapse. RESULTS: A total of 123 patients were identified to have EMI at diagnosis and 64 presented with EMI at relapse. The presence of EMI was associated with age ≤2 years, M5 morphology, abnormal karyotype, and KMT2A rearrangements. Hyperleukocytosis and complex karyotype were more prevalent in patients with EMI at relapse. Additionally, patients with EMI at diagnosis had a reduced incidence of FLT3 ITD-/NPM1+, whereas those with EMI at relapse displayed a lower frequency of FLT3 ITD+. Patients with EMI at diagnosis exhibited a lower complete remission (CR) rate at the end of Induction Course 1 and higher relapse incidence. Importantly, EMI at diagnosis independently predicted both shorter event-free survival (EFS) and overall survival (OS). Regarding relapse patients, the occurrence of EMI at relapse showed no impact on OS. However, relapse patients with myeloid sarcoma (MS)/no central nervous system (CNS) exhibited poorer OS compared to those with CNS/no MS. Furthermore, regarding patients with EMI at diagnosis, SCT failed to improve the survival, whereas GO treatment potentially enhanced OS. CONCLUSION: EMI at diagnosis is an independent adverse prognostic risk factor for pediatric AML, and GO treatment potentially improves survival for patients with EMI at diagnosis.

13.
Int J Oral Sci ; 16(1): 25, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38480698

RESUMO

Human with bi-allelic WNT10A mutations and epithelial Wnt10a knockout mice present enlarged pulp chamber and apical displacement of the root furcation of multi-rooted teeth, known as taurodontism; thus, indicating the critical role of Wnt10a in tooth root morphogenesis. However, the endogenous mechanism by which epithelial Wnt10a regulates Hertwig's epithelial root sheath (HERS) cellular behaviors and contributes to root furcation patterning remains unclear. In this study, we found that HERS in the presumptive root furcating region failed to elongate at an appropriate horizontal level in K14-Cre;Wnt10afl/fl mice from post-natal day 0.5 (PN0.5) to PN4.5. EdU assays and immunofluorescent staining of cyclin D1 revealed significantly decreased proliferation activity of inner enamel epithelial (IEE) cells of HERS in K14-Cre;Wnt10afl/fl mice at PN2.5 and PN3.5. Immunofluorescent staining of E-Cadherin and acetyl-α-Tubulin demonstrated that the IEE cells of HERS tended to divide perpendicularly to the horizontal plane, which impaired the horizontal extension of HERS in the presumptive root furcating region of K14-Cre;Wnt10afl/fl mice. RNA-seq and immunofluorescence showed that the expressions of Jag1 and Notch2 were downregulated in IEE cells of HERS in K14-Cre;Wnt10afl/fl mice. Furthermore, after activation of Notch signaling in K14-Cre;Wnt10afl/fl molars by Notch2 adenovirus and kidney capsule grafts, the root furcation defect was partially rescued. Taken together, our study demonstrates that an epithelial Wnt10a-Notch signaling axis is crucial for modulating HERS cell proper proliferation and horizontal-oriented division during tooth root furcation morphogenesis.


Assuntos
Raiz Dentária , Dente , Humanos , Feminino , Camundongos , Animais , Raiz Dentária/metabolismo , Odontogênese/genética , Transdução de Sinais , Esmalte Dentário , Células Epiteliais , Proteínas do Tecido Nervoso/metabolismo , Proteínas Wnt/metabolismo
14.
Chin J Dent Res ; 27(1): 53-63, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38546520

RESUMO

OBJECTIVE: To investigate FAM20A gene variants and histological features of amelogenesis imperfecta and to further explore the functional impact of these variants. METHODS: Whole-exome sequencing (WES) and Sanger sequencing were used to identify pathogenic gene variants in three Chinese families with amelogenesis imperfecta. Bioinformatics analysis, in vitro histological examinations and experiments were conducted to study the functional impact of gene variants, and the histological features of enamel, keratinised oral mucosa and dental follicle. RESULTS: The authors identified two nonsense variants c. 406C > T (p.Arg136*) and c.826C > T (p.Arg176*) in a compound heterozygous state in family 1, two novel frameshift variants c.936dupC (p.Val313Argfs*67) and c.1483dupC (p.Leu495Profs*44) in a compound heterozygous state in family 2, and a novel homozygous frameshift variant c.530_531insGGTC (p.Ser178Valfs*21) in family 3. The enamel structure was abnormal, and psammomatoid calcifications were identified in both the gingival mucosa and dental follicle. The bioinformatics and subcellular localisation analyses indicated these variants to be pathogenic. The secondary and tertiary structure analysis speculated that these five variants would cause structural damage to FAM20A protein. CONCLUSION: The present results broaden the variant spectrum and clinical and histological findings of diseases associated with FAM20A, and provide useful information for future genetic counselling and functional investigation.


Assuntos
Amelogênese Imperfeita , Proteínas do Esmalte Dentário , Humanos , Amelogênese Imperfeita/genética , Calcificação Fisiológica , Biologia Computacional , Esmalte Dentário , Proteínas do Esmalte Dentário/genética , População do Leste Asiático
15.
J Crit Care ; 82: 154792, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38554543

RESUMO

With increasing computing power, artificial intelligence (AI) and machine learning (ML) have prospered, which facilitate the analysis of large datasets, especially those found in critical care. It is important to define these terminologies, to inform a standardized approach to critical care research. This manuscript hopes to clarify these terms with examples from medical literature. Three major components that are required for a successful ML implementation: (i) reliable dataset, (ii) ML algorithm, and (iii) unbiased model evaluation, are discussed. A reliable dataset can be structured or unstructured with limited noise, outliers, and missing values. ML, a subset of AI, is typically focused on supervised or unsupervised learning tasks in which the output is based on inputs and derived from iterative pattern recognition algorithms, while AI is the overall ability of a machine to "think" or mimic human behavior; and to analyze data free from human influence. Even with successful implementation, advanced AI and ML algorithms have faced challenges in adoption into practice, mainly due to their lack of interpretability, which hinders trust, buy-in, and engagement from clinicians. Consequently, traditional algorithms, such as linear and logistic regression, that may have reduced predictive power but are highly interpretable, continue to be widely used.

16.
ACS Nano ; 18(13): 9584-9604, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38513119

RESUMO

Current cancer vaccines using T cell epitopes activate antitumor T cell immunity through dendritic cell/macrophage-mediated antigen presentation, but they lack the ability to promote B/CD4 T cell crosstalk, limiting their anticancer efficacy. We developed antigen-clustered nanovaccine (ACNVax) to achieve long-term tumor remission by promoting B/CD4 T cell crosstalk. The topographic features of ACNVax were achieved using an iron nanoparticle core attached with an optimal number of gold nanoparticles, where the clusters of HER2 B/CD4 T cell epitopes were conjugated on the gold surface with an optimal intercluster distance of 5-10 nm. ACNVax effectively trafficked to lymph nodes and cross-linked with BCR, which are essential for stimulating B cell antigen presentation-mediated B/CD4 T cell crosstalk in vitro and in vivo. ACNVax, combined with anti-PD-1, achieved long-term tumor remission (>200 days) with 80% complete response in mice with HER2+ breast cancer. ACNVax not only remodeled the tumor immune microenvironment but also induced a long-term immune memory, as evidenced by complete rejection of tumor rechallenge and a high level of antigen-specific memory B, CD4, and CD8 cells in mice (>200 days). This study provides a cancer vaccine design strategy, using B/CD4 T cell epitopes in an antigen clustered topography, to achieve long-term durable anticancer efficacy through promoting B/CD4 T cell crosstalk.


Assuntos
Vacinas Anticâncer , Nanopartículas Metálicas , Neoplasias , Camundongos , Animais , 60547 , Epitopos de Linfócito T , Ouro , Camundongos Endogâmicos C57BL , Linfócitos T CD8-Positivos , Vacinas Anticâncer/uso terapêutico , Microambiente Tumoral
17.
J Evid Based Med ; 17(1): 187-206, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38502879

RESUMO

BACKGROUND: Lumbar disc herniation (LDH), as one of the most common causes of lower back pain, imposes a heavy economic burden on patients and society. Conservative management is the first-line choice for the majority of LDH patients. Traditional Chinese medicine (TCM) is an important part of conservative treatment and has attracted more and more international attention. STUDY DESIGN: Evidence-based guideline. METHODS: We formed a guideline panel of multidisciplinary experts. The clinical questions were identified on the basis of a systematic literature search and a consensus meeting. We searched the literature for direct evidence on the management of LDH and assessed its certainty-generated recommendations using the grading of recommendations, assessment, development, and evaluation (GRADE) approach. RESULTS: The guideline panel made 20 recommendations, which covered the use of Shentong Zhuyu decoction, Shenzhuo decoction, Simiao San decoction, Duhuo Jisheng decoction, Yaobitong capsule, Yaotongning capsule, Osteoking, manual therapy, needle knife, manual acupuncture, electroacupuncture, Chinese exercise techniques (Tai Chi, Baduanjin, or Yijinjing), and integrative medicine, such as combined non-steroidal anti-inflammatory drugs, neural nutrition, and traction. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. CONCLUSION: This is the first LDH treatment guideline for TCM and integrative medicine with a systematic search, synthesis of evidence, and using the GRADE method to rate the quality of evidence. We hope these recommendations can help support healthcare workers caring for LDH patients.


Assuntos
Terapia por Acupuntura , Deslocamento do Disco Intervertebral , Humanos , Medicina Tradicional Chinesa/métodos , Deslocamento do Disco Intervertebral/tratamento farmacológico
18.
Bioorg Chem ; 146: 107322, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38555797

RESUMO

Porcine Delta Coronavirus (PDCoV) infection can induce serious dehydration, diarrhea and even death of piglets, which has caused huge losses to the breeding industry. PDCoV has been reported to have the potential for cross species transmission, and even reports of infecting humans have emerged. At present, there are still no effective prevention and control measures for PDCoV. In this study, we have designed and synthesized a series of unreported Dihydropteridone derivatives. All of these compounds were evaluated for the against PDCoV in vivo and in vitro for the first time. In this study, antiviral activity (17.34 ± 7.20 µM) and low cytotoxicity (>800 µM) was found in compound W8. Compound W8 exerts antiviral effect on PDCoV by inhibiting cell apoptosis and inflammatory factors caused by virus infection in vitro. In addition, lung and small intestinal lesions caused by PDCoV infection in mice could be significantly reduced by compound W8. These findings highlight the potential of compound W8 as a valuable therapeutic option against PDCoV infection, and lay a foundation for further research and development in this field.


Assuntos
Infecções por Coronavirus , Coronavirus , Sulfonamidas , Suínos , Animais , Humanos , Camundongos , Intestino Delgado , Antivirais/farmacologia
19.
J Appl Microbiol ; 135(4)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38520150

RESUMO

AIMS: In this study, the control effects of synthetic microbial communities composed of peanut seed bacteria against seed aflatoxin contamination caused by Aspergillus flavus and root rot by Fusarium oxysporum were evaluated. METHODS AND RESULTS: Potentially conserved microbial synthetic communities (C), growth-promoting synthetic communities (S), and combined synthetic communities (CS) of peanut seeds were constructed after 16S rRNA Illumina sequencing, strain isolation, and measurement of plant growth promotion indicators. Three synthetic communities showed resistance to root rot and CS had the best effect after inoculating into peanut seedlings. This was achieved by increased defense enzyme activity and activated salicylic acid (SA)-related, systematically induced resistance in peanuts. In addition, CS also inhibited the reproduction of A. flavus on peanut seeds and the production of aflatoxin. These effects are related to bacterial degradation of toxins and destruction of mycelia. CONCLUSIONS: Inoculation with a synthetic community composed of seed bacteria can help host peanuts resist the invasion of seeds by A. flavus and seedlings by F. oxysporum and promote the growth of peanut seedlings.


Assuntos
Aflatoxinas , Sementes , RNA Ribossômico 16S/genética , Sementes/microbiologia , Fungos/genética , Plântula/microbiologia , Bactérias/genética , Arachis/microbiologia
20.
Chem Commun (Camb) ; 60(31): 4206-4209, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38523529

RESUMO

A novel silyl radical-induced cascade silylation/cyclization of 1,7-dienes has been realized employing readily available hydrosilanes as a silicon source and Cu(I) salt as a catalyst. This protocol introduces diverse silicon fragments into a challenging 7-membered ring structure and provides an efficient approach to a wide array of biologically important silyl-substituted benzo[b]azepin-2-ones. Several control experiments suggest that the reaction undergoes a free radical process. The gram-scale synthesis and late-stage transformations further demonstrate the scalability and applicability of the reaction in organic synthesis.

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