Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 3.933
Filtrar
1.
ACS Sens ; 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38629405

RESUMO

Anisotropic strain sensors capable of multidirectional sensing are crucial for advanced sensor applications in human motion detection. However, current anisotropic sensors encounter challenges in achieving a balance among high sensitivity, substantial stretchability, and a wide linear detection range. To address these challenges, a facile freeze-casting strategy was employed to construct oriented filler networks composed of carbon nanotubes and conductive carbon black within a brominated butyl rubber ionomer (iBIIR) matrix. The resulting anisotropic sensor based on the iBIIR composites exhibited distinct gauge factors (GF) in the parallel and vertical directions (GF∥ = 4.91, while GF⊥ = 2.24) and a broad linear detection range over a strain range of 190%. This feature enables the sensor to detect various human activities, including uniaxial pulse, finder bending, elbow bending, and cervical spine movements. Moreover, the ion-cross-linking network within the iBIIR, coupled with strong π-cation interactions between the fillers and iBIIR macromolecules, imparted high strength (12.3 MPa, nearly twice that of pure iBIIR) and an ultrahigh elongation at break (>1800%) to the composites. Furthermore, the sensor exhibited exceptional antibacterial effectiveness, surpassing 99% against both Escherichia coli and Staphylococcus aureus. Notably, the sensor was capable of wireless sensing. It is anticipated that anisotropic sensors will have extensive application prospects in flexible wearable devices.

2.
Zhongguo Zhong Yao Za Zhi ; 49(3): 849-852, 2024 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-38621889

RESUMO

Chinese drug registration laws and regulations have always reserved a place for the new traditional Chinese medicine(TCM) drugs for syndromes, but so far no such new drugs have been approved for registration. This paper expounded on the relevant policies, regulations, and technologies of new TCM drugs for syndromes in China and pointed out that the application of the animal model of TCM syndromes to carry out pharmacodynamics research and clinical efficacy evaluation criteria of TCM syndromes were the main technical difficulties in the research and development of new TCM drugs for syndromes. Not all syndromes are suitable for developing new drugs, and the indications for new TCM drugs should be constant syndromes. Among the three research and development models of simple syndrome, syndrome-unified disease, and combined disease and syndrome, the research and development model of combined disease and syndrome is recommended. Clinical positioning is the key to new TCM drugs for syndromes. It is encouraged to conduct high-quality human use experience studies to determine the clinical positioning of new TCM drugs for syndromes, as well as the target population, dose, course of treatment, and initial therapeutic and safety, and apply for exemption from non-clinical effectiveness studies. Clinical trials of new TCM drugs for syndromes should take the target symptoms or signs as the main efficacy index and the efficacy of TCM syndromes as the secondary efficacy index. Clinical research program design should implement the "patient-centered" concept and introduce clinical outcome evaluation indicators. In the clinical safety evaluation, special conditions such as characteristic syndromes and changes should be considered. With the construction of the human use experience technology system and the promotion of the TCM registration and evaluation evidence system featuring the "combination of TCM theory, human use experience, and clinical trials", it is believed that many high-quality new TCM drugs for syndromes will be developed in the future.


Assuntos
Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Humanos , Pesquisa , Síndrome , China , Medicamentos de Ervas Chinesas/uso terapêutico
3.
Environ Sci Technol ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38623940

RESUMO

The environmental dissemination of extracellular antibiotic resistance genes (eARGs) in wastewater and natural water bodies has aroused growing ecological concerns. The coexisting chemical pollutants in water are known to markedly affect the eARGs transfer behaviors of the environmental microbial community, but the detailed interactions and specific impacts remain elusive so far. Here, we revealed a concentration-dependent impact of dimethyl phthalate (DMP) and several other types of phthalate esters (common water pollutants released from plastics) on the natural transformation of eARGs. The DMP exposure at an environmentally relevant concentration (10 µg/L) resulted in a 4.8-times raised transformation frequency of Acinetobacter baylyi but severely suppressed the transformation at a high concentration (1000 µg/L). The promotion by low-concentration DMP was attributed to multiple mechanisms, including increased bacterial mobility and membrane permeability to facilitate eARGs uptake and improved resistance of the DMP-bounded eARGs (via noncovalent interaction) to enzymatic degradation (with suppressed DNase activity). Similar promoting effects of DMP on the eARGs transformation were also found in real wastewater and biofilm systems. In contrast, higher-concentration DMP suppressed the eARGs transformation by disrupting the DNA structure. Our findings highlight a potentially underestimated eARGs spreading in aquatic environments due to the impacts of coexisting chemical pollutants and deepen our understanding of the risks of biological-chemical combined pollution in wastewater and environmental water bodies.

5.
Small Methods ; : e2400015, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38607951

RESUMO

Nowadays, the extensively used lead sulfide (PbS) quantum dot (QD) hole transport layer (HTL) relies on layer-by-layer method to replace long chain oleic acid (OA) ligands with short 1,2-ethanedithiol (EDT) ligands for preparation. However, the inevitable significant volume shrinkage caused by this traditional method will result in undesired cracks and disordered QD arrangement in the film, along with adverse increased defect density and inhomogeneous energy landscape. To solve the problem, a novel method for EDT passivated PbS QD (PbS-EDT) HTL preparation using small-sized benzoic acid (BA) as intermediate ligands is proposed in this work. BA is substituted for OA ligands in solution followed by ligand exchange with EDT layer by layer. With the new method, smoother PbS-EDT films with more ordered and closer QD packing are gained. It is demonstrated stronger coupling between QDs and reduced defects in the QD HTL owing to the intermediate BA ligand exchange. As a result, the suppressed nonradiative recombination and enhanced carrier mobility are achieved, contributing to ≈20% growth in short circuit current density (Jsc) and a 23.4% higher power conversion efficiency (PCE) of 13.2%. This work provides a general framework for layer-by-layer QD film manufacturing optimization.

6.
Huan Jing Ke Xue ; 45(5): 3047-3058, 2024 May 08.
Artigo em Chinês | MEDLINE | ID: mdl-38629565

RESUMO

In order to comprehensively evaluate the effects of vermicomposting on compost quality and the conversion of heavy metals under different control conditions, 109 studies were reviewed. The effects of earthworm species, pre-compost time, ventilation methods, initial C/N, initial pH, and initial moisture of the raw materials on compost quality and the heavy metal toxicity were quantitatively discussed during the vermicomposting process through Meta-analysis. The results showed that the six subgroups of factors all showed obvious influences on the compost quality and heavy metal toxicity. After vermicomposting, the contents of NO3--N (116.2%), TN (29.1%), TP (31.2%), and TK (15.0%) were significantly increased, whereas NH4+-N (-14.8%) and C/N (-36.3%) were significantly decreased. Meanwhile, the total amount of Cu and Cr of the final compost and their bioavailability were significantly reduced. Considering the influences of grouping factors on compost quality and heavy metals, it is recommended to adjust the initial moisture of pile materials to 70%-80%, C/N to 30-85, and pH to 6-7 and to conduct pre-composting for 0-15 d; additionally, vermicomposting should be naturally placed when the composting is aimed at promoting the compost quality. If the main purpose is to weaken the perniciousness of heavy metals in the raw material, it is recommended to adjust the initial moisture of the material to 50%-60%, C/N to less than 30, and pH to 7-8; to conduct no pre-compost; regularly turn the piles; and use the earthworm Eudrilus eugeniae for vermicomposting.


Assuntos
Compostagem , Metais Pesados , Oligoquetos , Animais , Solo/química , Esgotos/química , Metais Pesados/análise
7.
BMC Cancer ; 24(1): 444, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38600507

RESUMO

BACKGROUND: Transforming growth factor-ß (TGF-ß) is a cytokine with multiple functions, including cell growth regulation, extracellular matrix production, angiogenesis homeostasis adjustment and et al. TGF-ß pathway activation promotes tumor metastasis/progression and mediates epithelial-mesenchymal transmission suppressing immunosurveillance in advanced tumors. GFH018, a small molecule inhibitor blocking TGF-ß signal transduction, inhibits the progression and/or metastasis of advanced cancers. This first-in-human study evaluated the safety, tolerability, pharmacokinetics (PK), and efficacy of GFH018 monotherapy in patients with advanced solid tumors. METHODS: This phase I, open-label, multicenter study used a modified 3+3 dose escalation and expansion design. Adult patients with advanced solid tumors failing the standard of care were enrolled. Starting at 5 mg, eight dose levels up to 85 mg were evaluated. Patients received GFH018 BID (14d-on/14d-off) starting on the 4th day after a single dose on cycle 1, day 1. Subsequent cycles were defined as 28 days. The study also explored the safety of 85 mg BID 7d-on/7d-off. Adverse events were graded using NCI criteria for adverse events (NCI-CTCAE v5.0). PK was analyzed using a noncompartmental method. Efficacy was evaluated using RECIST 1.1. Blood samples were collected for biomarker analysis. RESULTS: Fifty patients were enrolled and received at least one dose of GFH018. No dose-limiting toxicity occurred, and the maximum tolerated dose was not reached. Forty-three patients (86.0%) had at least one treatment-related adverse event (TRAE), and three patients (6.0%) had ≥ G3 TRAEs. The most common TRAEs (any grade/grade ≥3) were AST increased (18%/0%), proteinuria (14%/2%), anemia (14%/2%), and ALT increased (12%/0%). No significant cardiotoxicity or bleeding was observed. GFH018 PK was linear and dose-independent, with a mean half-life of 2.25-8.60 h from 5 - 85 mg. Nine patients (18.0%) achieved stable disease, and one patient with thymic carcinoma achieved tumor shrinkage, with the maximum target lesion decreased by 18.4%. Serum TGF-ß1 levels were not associated with clinical responses. The comprehensive recommended dose for Phase II was defined as 85 mg BID 14d-on/14d-off. CONCLUSIONS: GFH018 monotherapy presented a favorable safety profile without cardiac toxicity or bleeding. Modest efficacy warrants further studies, including combination strategies. TRIAL REGISTRATION: ClinicalTrial. gov ( https://www. CLINICALTRIALS: gov/ ), NCT05051241. Registered on 2021-09-02.


Assuntos
Neoplasias , Receptores de Fatores de Crescimento Transformadores beta , Adulto , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Critérios de Avaliação de Resposta em Tumores Sólidos , Fator de Crescimento Transformador beta , Receptores de Fatores de Crescimento Transformadores beta/antagonistas & inibidores
8.
Nat Commun ; 15(1): 3231, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622167

RESUMO

Engineering atom-scale sites are crucial to the mitigation of polysulfide shuttle, promotion of sulfur redox, and regulation of lithium deposition in lithium-sulfur batteries. Herein, a homonuclear copper dual-atom catalyst with a proximal distance of 3.5 Å is developed for lithium-sulfur batteries, wherein two adjacent copper atoms are linked by a pair of symmetrical chlorine bridge bonds. Benefiting from the proximal copper atoms and their unique coordination, the copper dual-atom catalyst with the increased active interface concentration synchronously guide the evolutions of sulfur and lithium species. Such a delicate design breaks through the activity limitation of mononuclear metal center and represents a catalyst concept for lithium-sulfur battery realm. Therefore, a remarkable areal capacity of 7.8 mA h cm-2 is achieved under the scenario of sulfur content of 60 wt.%, mass loading of 7.7 mg cm-2 and electrolyte dosage of 4.8 µL mg-1.

9.
Colloids Surf B Biointerfaces ; 238: 113888, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38599077

RESUMO

Gallium (Ga) is a well-known liquid metals (LMs) that possesses the features, such as fluidity, low viscosity, high electrical and thermal conductivity, and relative low toxicity. Owing to the weak interactions between Ga atoms, Ga LMs can be adopted for fabrication of various Ga LMs-based functional materials via ultrasonic treatment and mechanical grinding. Moreover, many organic compounds/polymers can be coated on the surface of LMs-based materials through coordination between oxidized outlayers of Ga LMs and functional groups of organic components. Over the past decades, different strategies have been reported for synthesizing Ga LMs-based functional materials and their biomedical applications have been intensively investigated. Although some review articles have published over the past few years, a concise review is still needed to advance the latest developments in biomedical fields. The main context can be majorly divided into two parts. In the first section, various strategies for fabrication of Ga LMs-based functional materials via top-down strategies were introduced and discussed. Following that, biomedical applications of Ga LMs-based functional materials were summarized and design Ga LMs-based functional materials with enhanced performance for cancer photothermal therapy (PTT) and PTT combined therapy were highlighted. We trust this review article will be beneficial for scientists to comprehend this promising field and greatly advance future development for fabrication of other Ga LMs-based functional materials with better performance for biomedical applications.

10.
Artigo em Inglês | MEDLINE | ID: mdl-38593836

RESUMO

We theoretically study the crossed Andreev reflection (CAR) of the normal mental-superconductor-normal mental (NSN) heterojunction based on Kekulé-Y patterned graphene with two doping types of the right region, i.e., nSn and nSp configurations. It is found that the enhanced CAR is more likely to occur in the nSp configuration rather than the nSn configuration. To be concrete, the almost perfect CAR occurs in a large range of incident angle in the single Dirac cone phase when the incident energy is inside the gap of the nonlinear band. Furthermore, the roles of the length of superconductor and pseudospin-valley coupling on conductance are also evaluated. .

11.
bioRxiv ; 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38617277

RESUMO

Optineurin (OPTN) mutations are linked to amyotrophic lateral sclerosis (ALS) and normal tension glaucoma (NTG), but a relevant animal model is lacking, and the molecular mechanisms underlying neurodegeneration are unknown. We found that OPTN C-terminus truncation (OPTNΔC) causes late-onset neurodegeneration of retinal ganglion cells (RGCs), optic nerve (ON), and spinal cord motor neurons, preceded by a striking decrease of axonal mitochondria. Surprisingly, we discover that OPTN directly interacts with both microtubules and the mitochondrial transport complex TRAK1/KIF5B, stabilizing them for proper anterograde axonal mitochondrial transport, in a C- terminus dependent manner. Encouragingly, overexpressing OPTN/TRAK1/KIF5B reverses not only OPTN truncation-induced, but also ocular hypertension-induced neurodegeneration, and promotes striking ON regeneration. Therefore, in addition to generating new animal models for NTG and ALS, our results establish OPTN as a novel facilitator of the microtubule-dependent mitochondrial transport necessary for adequate axonal mitochondria delivery, and its loss as the likely molecular mechanism of neurodegeneration.

12.
Nano Lett ; 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38619280

RESUMO

Developing highly active yet stable catalysts for the hydrogen oxidation reaction (HOR) in alkaline media remains a significant challenge. Herein, we designed a novel catalyst of atomic PtPd-layer shelled ultrasmall PdCu hollow nanoparticles (HPdCu NPs) on partially unzipped carbon nanotubes (PtPd@HPdCu/W-CNTs), which can achieve a high mass activity, 5 times that of the benchmark Pt/C, and show exceptional stability with negligible decay after 20,000 cycles of accelerated degradation test. The atomically thin PtPd shell serves as the primary active site for the HOR and a protective layer that prevents Cu leaching. Additionally, the HPdCu substrate not only tunes the adsorption properties of the PtPd layer but also prevents corrosive Pt from reaching the interface between NPs and the carbon support, thereby mitigating carbon corrosion. This work introduces a new strategy that leverages the distinct advantages of multiple components to address the challenges associated with slow kinetics and poor durability toward the HOR.

13.
Opt Express ; 32(7): 10786-10800, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38570944

RESUMO

As a new type of active Earth observation technology, airborne hyperspectral lidar combines the advantages of traditional lidar 3D information acquisition and passive hyperspectral imaging technology, and it can achieve integrated imaging detection with a high spatial and hyperspectral resolution. Thus, it has become an important future direction of Earth surface remote sensing technology. This article introduces the design and development of an airborne hyperspectral imaging lidar system. The hyperspectral lidar adopts a focal plane splitting method, combined with an array of 168 optical fibers, to couple wide-spectral-range laser echo signals one by one to the corresponding single tube detector, achieving efficient splitting and precise coupling of supercontinuum laser pulse echo signals. This article proposes a fast synchronous calibration method that is suitable for hyperspectral imaging lidar systems. Results show that the spectral range of the hyperspectral lidar system is 400-900 nm, and the spectral resolution of single-fiber detection is greater than 3 nm. Notably, this article focuses on analyzing the abnormal detection channels based on the calibration results. With the test results of adjacent channels combined, the reason for the abnormal spectral bandwidth of channel 17 is analyzed as an example. This research points out the direction for verifying the design parameters of the hyperspectral lidar prototype and lays an important foundation for airborne flight test of the hyperspectral lidar.

14.
Lipids Health Dis ; 23(1): 101, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38600581

RESUMO

BACKGROUND: The objective was to investigate the efficacy of different doses of levothyroxine therapy among pregnant women exhibiting high-normal thyroid stimulating hormone levels and positive thyroid peroxidase antibodies throughout the first half of pregnancy. METHODS: Pregnant women exhibiting high-normal thyroid stimulating hormone levels and thyroid peroxidase antibodies positivity throughout the initial half of pregnancy were selected from January 2021 to September 2023. Based on the different doses of levothyroxine, the pregnant women were categorized into the nonintervention group (G0, 122 women), 25 µg levothyroxine intervention group (G25, 69 women), and 50 µg levothyroxine intervention group (G50, 58 women). Serum parameters, gastrointestinal symptoms, small intestinal bacterial overgrowth (SIBO), maternal and neonatal outcomes were compared after the intervention among the three groups. RESULTS: After the intervention, in the G25 and G50 groups, the thyroid stimulating hormone, triglyceride and low-density lipoprotein levels were notably less in contrast to those in the G0 group (P < 0.05). The rates of abdominal distension and SIBO in the G25 and G50 groups were notably lower in contrast to the G0 group (P = 0.043 and 0.040, respectively). The G50 group had a lower rate of spontaneous abortion and premature membrane rupture than the G0 group (P = 0.01 and 0.015, respectively). Before 11+ 2 weeks of gestation and at thyroid peroxidase antibodies levels ≥ 117 IU/mL, in contrast to the G0 group, the G50 group experienced a decreased rate of spontaneous abortion (P = 0.008). The G50 group had significantly higher newborn weight than the G0 group (P = 0.014), as well as a notably longer newborn length than the G0 and G25 groups (P = 0.005). CONCLUSIONS: For pregnant women with high-normal thyroid stimulating hormone levels and thyroid peroxidase antibodies positive during the first half of pregnancy, supplementation with 50 µg levothyroxine was more effective in improving their blood lipid status and gastrointestinal symptoms, reducing the incidence of SIBO and premature rupture of membranes, and before 11+2 weeks, TPOAb ≥ 117 IU/mL proved more beneficial in mitigating the risk of spontaneous abortion.


Assuntos
Aborto Espontâneo , Tiroxina , Recém-Nascido , Feminino , Gravidez , Humanos , Tiroxina/uso terapêutico , Gestantes , Iodeto Peroxidase , Autoanticorpos , Tireotropina
15.
Brief Bioinform ; 25(3)2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38600663

RESUMO

Protein sequence design can provide valuable insights into biopharmaceuticals and disease treatments. Currently, most protein sequence design methods based on deep learning focus on network architecture optimization, while ignoring protein-specific physicochemical features. Inspired by the successful application of structure templates and pre-trained models in the protein structure prediction, we explored whether the representation of structural sequence profile can be used for protein sequence design. In this work, we propose SPDesign, a method for protein sequence design based on structural sequence profile using ultrafast shape recognition. Given an input backbone structure, SPDesign utilizes ultrafast shape recognition vectors to accelerate the search for similar protein structures in our in-house PAcluster80 structure database and then extracts the sequence profile through structure alignment. Combined with structural pre-trained knowledge and geometric features, they are further fed into an enhanced graph neural network for sequence prediction. The results show that SPDesign significantly outperforms the state-of-the-art methods, such as ProteinMPNN, Pifold and LM-Design, leading to 21.89%, 15.54% and 11.4% accuracy gains in sequence recovery rate on CATH 4.2 benchmark, respectively. Encouraging results also have been achieved on orphan and de novo (designed) benchmarks with few homologous sequences. Furthermore, analysis conducted by the PDBench tool suggests that SPDesign performs well in subdivided structures. More interestingly, we found that SPDesign can well reconstruct the sequences of some proteins that have similar structures but different sequences. Finally, the structural modeling verification experiment indicates that the sequences designed by SPDesign can fold into the native structures more accurately.


Assuntos
Redes Neurais de Computação , Proteínas , Alinhamento de Sequência , Sequência de Aminoácidos , Proteínas/química , Análise de Sequência de Proteína/métodos
16.
Biomed Environ Sci ; 37(2): 157-169, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38582978

RESUMO

Objective: China is among the 30 countries with a high burden of tuberculosis (TB) worldwide, and TB remains a public health concern. Kashgar Prefecture in the southern Xinjiang Autonomous Region is considered as one of the highest TB burden regions in China. However, molecular epidemiological studies of Kashgar are lacking. Methods: A population-based retrospective study was conducted using whole-genome sequencing (WGS) to determine the characteristics of drug resistance and the transmission patterns. Results: A total of 1,668 isolates collected in 2020 were classified into lineages 2 (46.0%), 3 (27.5%), and 4 (26.5%). The drug resistance rates revealed by WGS showed that the top three drugs in terms of the resistance rate were isoniazid (7.4%, 124/1,668), streptomycin (6.0%, 100/1,668), and rifampicin (3.3%, 55/1,668). The rate of rifampicin resistance was 1.8% (23/1,290) in the new cases and 9.4% (32/340) in the previously treated cases. Known resistance mutations were detected more frequently in lineage 2 strains than in lineage 3 or 4 strains, respectively: 18.6% vs. 8.7 or 9%, P < 0.001. The estimated proportion of recent transmissions was 25.9% (432/1,668). Multivariate logistic analyses indicated that sex, age, occupation, lineage, and drug resistance were the risk factors for recent transmission. Despite the low rate of drug resistance, drug-resistant strains had a higher risk of recent transmission than the susceptible strains (adjusted odds ratio, 1.414; 95% CI, 1.023-1.954; P = 0.036). Among all patients with drug-resistant tuberculosis (DR-TB), 78.4% (171/218) were attributed to the transmission of DR-TB strains. Conclusion: Our results suggest that drug-resistant strains are more transmissible than susceptible strains and that transmission is the major driving force of the current DR-TB epidemic in Kashgar.


Assuntos
Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos , Humanos , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Rifampina/farmacologia , Estudos Retrospectivos , Farmacorresistência Bacteriana Múltipla/genética , Testes de Sensibilidade Microbiana , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Mutação
17.
J Environ Manage ; 358: 120895, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38626487

RESUMO

Microbial inoculation plays a significant role in promoting the efficiency of biowaste conversion. This study investigates the function of Streptomyces-Bacillus Inoculants (SBI) on carbon (C) and nitrogen (N) conversion, and microbial dynamics, during cow manure (10% and 20% addition) and corn straw co-composting. Compared to inoculant-free controls, inoculant application accelerated the compost's thermophilic stage (8 vs 15 days), and significantly increased compost total N contents (+47%) and N-reductase activities (nitrate reductase: +60%; nitrite reductase: +219%). Both bacterial and fungal community succession were significantly affected by DOC, urease, and NH4+-N, while the fungal community was also significantly affected by cellulase. The contribution rate of Cupriavidus to the physicochemical factors of compost was as high as 83.40%, but by contrast there were no significantly different contributions (∼60%) among the top 20 fungal genera. Application of SBI induced significant correlations between bacteria, compost C/N ratio, and catalase enzymes, indicative of compost maturation. We recommend SBI as a promising bio-composting additive to accelerate C and N turnover and high-quality biowaste maturation. SBI boosts organic cycling by transforming biowastes into bio-fertilizers efficiently. This highlights the potential for SBI application to improve plant growth and soil quality in multiple contexts.

18.
Nat Med ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627559

RESUMO

Cancer of unknown primary (CUP) site poses diagnostic challenges due to its elusive nature. Many cases of CUP manifest as pleural and peritoneal serous effusions. Leveraging cytological images from 57,220 cases at four tertiary hospitals, we developed a deep-learning method for tumor origin differentiation using cytological histology (TORCH) that can identify malignancy and predict tumor origin in both hydrothorax and ascites. We examined its performance on three internal (n = 12,799) and two external (n = 14,538) testing sets. In both internal and external testing sets, TORCH achieved area under the receiver operating curve values ranging from 0.953 to 0.991 for cancer diagnosis and 0.953 to 0.979 for tumor origin localization. TORCH accurately predicted primary tumor origins, with a top-1 accuracy of 82.6% and top-3 accuracy of 98.9%. Compared with results derived from pathologists, TORCH showed better prediction efficacy (1.677 versus 1.265, P < 0.001), enhancing junior pathologists' diagnostic scores significantly (1.326 versus 1.101, P < 0.001). Patients with CUP whose initial treatment protocol was concordant with TORCH-predicted origins had better overall survival than those who were administrated discordant treatment (27 versus 17 months, P = 0.006). Our study underscores the potential of TORCH as a valuable ancillary tool in clinical practice, although further validation in randomized trials is warranted.

19.
Hepatol Commun ; 8(4)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38573832

RESUMO

BACKGROUND: Sorafenib is the first-line therapy for patients with advanced-stage HCC, but its clinical cure rate is unsatisfactory due to adverse reactions and drug resistance. Novel alternative strategies to overcome sorafenib resistance are urgently needed. Oxyberberine (OBB), a major metabolite of berberine in vivo, exhibits potential antitumor potency in various human malignancies, including liver cancer. However, it remains unknown whether and how OBB sensitizes liver cancer cells to sorafenib. METHODS: Cell viability, trypan blue staining and flow cytometry assays were employed to determine the synergistic effect of OBB and sorafenib on killing HCC cells. PCR, western blot, co-immunoprecipitation and RNA interference assays were used to decipher the mechanism by which OBB sensitizes sorafenib. HCC xenograft models and clinical HCC samples were utilized to consolidate our findings. RESULTS: We found for the first time that OBB sensitized liver cancer cells to sorafenib, enhancing its inhibitory effect on cell growth and induction of apoptosis in vitro. Interestingly, we observed that OBB enhanced the sensitivity of HCC cells to sorafenib by reducing ubiquitin-specific peptidase 7 (USP7) expression, a well-known tumor-promoting gene. Mechanistically, OBB inhibited notch homolog 1-mediated USP7 transcription, leading to the downregulation of V-Myc avian myelocytomatosis viral oncogene homolog (c-Myc), which synergized with sorafenib to suppress liver cancer. Furthermore, animal results showed that cotreatment with OBB and sorafenib significantly inhibited the tumor growth of liver cancer xenografts in mice. CONCLUSIONS: These results indicate that OBB enhances the sensitivity of liver cancer cells to sorafenib through inhibiting notch homolog 1-USP7-c-Myc signaling pathway, which potentially provides a novel therapeutic strategy for liver cancer to improve the effectiveness of sorafenib.


Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Animais , Camundongos , Sorafenibe/farmacologia , Peptidase 7 Específica de Ubiquitina/metabolismo , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteínas Proto-Oncogênicas c-myc/farmacologia , Transdução de Sinais , Linhagem Celular Tumoral , Receptor Notch1/uso terapêutico
20.
Int J Cardiol Cardiovasc Risk Prev ; 21: 200265, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38577011

RESUMO

Background: The present study aimed to develop and validate a prediction nomogram model for 5-year all-cause mortality in diabetic patients with hypertension. Methods: Data were extracted from the National Health and Nutrition Examination Survey (NHANES). A total of 3291 diabetic patients with hypertension in the NHANES cycles for 1999-2014 were selected and randomly assigned at a ratio of 8:2 to the training cohort (n = 2633) and validation cohort (n = 658). Multivariable Cox regression was conducted to establish a visual nomogram model for predicting the risk of 5-year all-cause mortality. Receiver operating characteristic curves and C-indexes were used to evaluate the discriminant ability of the prediction nomogram model for all-cause mortality. Survival curves were created using the Kaplan-Meier method and compared by the log-rank test. Results: The nomogram model included eight independent predictors: age, sex, education status, marital status, smoking, serum albumin, blood urea nitrogen, and previous cardiovascular disease. The C-indexes for the model in the training and validation cohorts were 0.76 (95% confidence interval: 0.73-0.79, p < 0.001) and 0.75 (95% confidence interval: 0.69-0.81, p < 0.001), respectively. The calibration curves indicated that the model had satisfactory consistency in the two cohorts. The risk of all-cause mortality gradually increased as the tertiles of the nomogram model score increased (log-rank test, p < 0.001). Conclusion: The newly developed nomogram model, a readily useable and efficient tool to predict the risk of 5-year all-cause mortality in diabetic patients with hypertension, provides a novel risk stratification method for individualized intervention.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...