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1.
Mil Med ; 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39091078

RESUMO

OBJECTIVE: The present study investigated the impact of continuous infusion therapy with low-dose terlipressin (TP) combined with norepinephrine on hemodynamics, inflammatory markers, and prognosis in patients with severe septic shock. MATERIALS AND METHODS: Seventy-four patients with severe septic shock were randomly assigned to either a control group (n = 37) or an observation group (n = 37). Patients in the control group received norepinephrine alone, while those in the observation group received a continuous infusion of low-dose TP in addition to norepinephrine. To assess the effect of treatment, a set of clinical parameters was evaluated in both groups before and after treatment. These parameters included hemodynamic indicators (heart rate [HR], mean arterial pressure [MAP], central venous pressure [CVP], cardiac index [CI], and systemic vascular resistance index [SVRI]), levels of serum inflammatory markers (interleukin-8 [IL-8], tumor necrosis factor-α [TNF-α], and hypersensitivity C-reactive protein [hs-CRP]), renal function indicators (blood urea nitrogen [BUN], serum creatinine [SCr], and cystatin C [Cys-C]), serum procalcitonin (PCT), and lactate, as well as lactate clearance rate (LCR). Additionally, the acute physiology and chronic health evaluation II (APACHE II) score, 28-day mortality rate, multiple organ dysfunction syndrome (MODS) incidence rate, and adverse reaction incidence were also determined. RESULTS: Compared to baseline values, MAP, CVP, CI, SVRI, and LCR increased in both groups after treatment, while HR, levels of IL-8, TNF-α, hs-CRP, BUN, SCr, PCT, and lactate all decreased. Additionally, APACHE II scores also decreased. Furthermore, the observation group exhibited higher MAP, CVP, CI, SVRI, and LCR, along with lower HR, levels of IL-8, TNF-α, hs-CRP, BUN, SCr, PCT, and lactate than the control group after treatment. The observation group also had lower APACHE II score, 28-day mortality rate, MODS incidence rate, and adverse reaction incidence than the control group after treatment (P < .05). CONCLUSION: Continuous infusion therapy with low-dose TP combined with norepinephrine was effective in treating patients with severe septic shock, improving hemodynamic parameters, reducing the levels of inflammatory markers, promoting renal function recovery, and reducing the mortality rate.

2.
Nanomicro Lett ; 16(1): 268, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39136800

RESUMO

The eye, a complex organ isolated from the systemic circulation, presents significant drug delivery challenges owing to its protective mechanisms, such as the blood-retinal barrier and corneal impermeability. Conventional drug administration methods often fail to sustain therapeutic levels and may compromise patient safety and compliance. Polysaccharide-based microneedles (PSMNs) have emerged as a transformative solution for ophthalmic drug delivery. However, a comprehensive review of PSMNs in ophthalmology has not been published to date. In this review, we critically examine the synergy between polysaccharide chemistry and microneedle technology for enhancing ocular drug delivery. We provide a thorough analysis of PSMNs, summarizing the design principles, fabrication processes, and challenges addressed during fabrication, including improving patient comfort and compliance. We also describe recent advances and the performance of various PSMNs in both research and clinical scenarios. Finally, we review the current regulatory frameworks and market barriers that are relevant to the clinical and commercial advancement of PSMNs and provide a final perspective on this research area.

3.
Adv Mater ; : e2406915, 2024 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-39096070

RESUMO

Phase change materials (PCMs) are crucial for sustainable thermal management in energy-efficient construction and cold chain logistics, as they can store and release renewable thermal energy. However, traditional PCMs suffer from leakage and a loss of formability above their phase change temperatures, limiting their shape stability and versatility. Inspired by the muscle structure, formable PCMs with a hierarchical structure and solvent-responsive supramolecular networks based on polyvinyl alcohol (PVA)/wood composites are developed. The material, in its hydrated state, demonstrates low stiffness and pliability due to the weak hydrogen bonding between aligned wood fibers and PVA molecules. Through treatment of poly(ethylene glycol) (PEG) into the PVA/wood PEG gel (PEG/PVA/W) with strengthened hydrogen bonds, the resulting wood-based PCMs in the hard and melting states elevate the tensile stress from 10.14 to 80.86 MPa and the stiffness from 420 MPa to 4.8 GPa, making it 530 times stiffer than the PEG/PVA counterpart. Capable of morphing in response to solvent changes, these formable PCMs enable intricate designs for thermal management. Furthermore, supported by a comprehensive life cycle assessment, these shape-adaptable, recyclable, and biodegradable PCMs with lower environmental footprint present a sustainable alternative to conventional plastics and thermal management materials.

4.
Food Chem ; 460(Pt 3): 140737, 2024 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-39116771

RESUMO

In order to achieve rapid and effective identification of Hebei yam, a qualitative discrimination model was constructed based on near infrared (NIR), mid infrared (MIR), and microscopic Raman spectra in combination with individual spectra and multispectral data fusion strategies. The results showed that the gray wolf optimizer-support vector machine (GWO-SVM) model constructed by mid-level fusion using the three feature spectra performed the best in distinguishing the geographic origin of the yam, with a prediction accuracy of 100.00% in both the training set and the test set, and an F1 score of 1.00. The results indicated that due to spectral complementarity, NIR, MIR and Raman combined with feature-level fusion can be used as a powerful, non-destructive, fast and feasible tool for geographic origin classification and brand protection of Hebei yam. This work is expected to be a potential method for origin identification analysis and quality monitoring in the food and pharmaceutical industries.

5.
Biol Reprod ; 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39101465

RESUMO

Interleukin-32 is a species-specific cytokine that plays an important role in inflammation, cancer, and other diseases; however, its role in reproductive and pregnancy-related diseases remains unknown. This study aimed to investigate the role of interleukin-32 in reproductive and pregnancy-related diseases. Placental tissues from patients with pregnancy-induced hypertension, healthy pregnant women, and trophoblast lines were analysed. Interleukin-32 expression was quantified via polymerase chain reaction and immunohistochemistry, and functional assays were performed after interleukin-32 modulation. Interleukin-32 was identified only in placental mammals, such as Carnivora, Cetartiodactyla, Chiroptera, Dermoptera, Lagomorpha, Perissodactyla, and Primates via bioinformatics. Immunohistochemistry and polymerase chain reaction revealed that interleukin-32 was highly expressed in human placental villi, poorly expressed in decidua and endometrial tissues, and was not detected in mouse tissues. Second, interleukin-32 upregulates miR-205 expression by increasing DROSHA expression, and miR-205 promotes interleukin-32 expression by targeting its promoter region. Interleukin-32 and miR-205 significantly enhanced the invasion ability of HTR8/SVneo cells (a trophoblast cell line) and the tube formation ability of human umbilical vein endothelial cells. Through quantitative reverse transcription polymerase chain reaction and western blotting, the interleukin-32/miR-205 loop increased MMP2 and MMP9 expression in HTR-8/SVneo cells via the nuclear factor kappa B signalling pathway. Finally, using quantitative reverse transcription polymerase chain reaction, interleukin-32 and miR-205 expression levels were significantly lower in the placentas of patients with pregnancy-induced hypertension than in women with normal pregnancies. In conclusion, interleukin-32 regulates trophoblast invasion through the miR-205-nuclear factor kappa B-MMP2/9 pathway, which is involved in pregnancy-induced hypertension.

6.
Chin Herb Med ; 16(3): 344-357, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39072207

RESUMO

The genus Hippocampus is a multi-origin animal species with high medicinal and healthcare values. About 57 species of Hippocampus spread worldwide, of which about 14 species can be used as medicine, showing anti-oxidation, anti-inflammation, anti-depressant, anti-hypertension, anti-prostatic hyperplasia, antivirus, anti-apoptotic, antifatigue, and so on. And those pharmacological effects are mainly related to their active ingredients, including amino acids, abundant proteins (peptides and oligopeptides), fatty acids, nucleosides, steroids, and other small molecular compounds. The main means of authentication of Hippocampus species are morphological identification, microscopic identification, thin layer chromatography method, fingerprint method and genomics method. This review will provide useful insight for exploration, further study and precise medication of Hippocampus in the future.

7.
ACS Chem Biol ; 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39014961

RESUMO

Pseudouridine (Ψ) is a widespread RNA modification found in various RNA species, including rRNA, tRNA, snRNA, mRNA, and long noncoding RNA (lncRNA). Understanding the function of Ψ in these RNA types requires a robust method for the detection and quantification of the Ψ level at single-nucleotide resolution. A previously used method utilizes Ψ labeling by N-cyclohexyl-N'-ß-(4-methylmorpholinium)ethylcarbodiimide (CMC). The quantification of Ψ is based on the stop ratio after reverse transcription. However, the use of CMC followed by strong alkaline treatment causes severe RNA degradation, often requiring a large amount of RNA. The removal of CMC and recovery of RNA by ethanol precipitation are also time-consuming. Here, we introduce a Bisulfite Incorporation Hindered ligation-based method (BIHIND), which can detect and quantify Ψ sites on rRNA, mRNA, and noncoding RNA. BIHIND can be coupled with quantitative PCR (BIHIND-qPCR) for quantitative detection of Ψ fraction at individual modification sites, as well as with next-generation sequencing (BIHIND-seq) for high-throughput sequencing of Ψ without requiring reverse transcription. We validated the robustness of BIHIND with the elucidation of Ψ dynamics following pseudouridine synthase depletion.

8.
Infect Med (Beijing) ; 3(2): 100114, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38974346

RESUMO

Background: Hand, foot, and mouth disease (HFMD) is a common childhood infectious disease caused by a variety of enteroviruses (EVs). To explore the epidemiological characteristics and etiology of HFMD in Zhengzhou, China, we conducted a systematic analysis of HFMD surveillance data from Zhengzhou Center for Disease Control and Prevention from January 2009 to December 2021 (https://wjw.zhengzhou.gov.cn/). Methods: Surveillance data were collected from Zhengzhou Center for Disease Control and Prevention from January 2009 to December 2021 (https://wjw.zhengzhou.gov.cn/). Cases were analyzed according to the time of onset, type of diagnosis, characteristics, viral serotype, and epidemiological trends. Results: We found that the primary causative agent responsible for the HFMD outbreaks in Zhengzhou was Enterovirus A71 (EVA-71) (48.56%) before 2014. After 2015, other EVs gradually became the dominant strains (57.68%). The data revealed that the HFMD epidemics in Zhengzhou displayed marked seasonality, with major peaks occurring from April to June, followed by secondary peaks from October to November, except in 2020. Both the severity and case-fatality ratio of HFMD decreased following the COVID-19 pandemic (severity ‰: 13.46 vs. 0.17; case-fatality ‰: 0.21 vs. 0, respectively). Most severe cases were observed in patients aged 1 year and below, accounting for 45.81%. Conclusions: Overall, the incidence rate of HFMD decreased in Zhengzhou following the introduction of the EVA-71 vaccine in 2016. However, it is crucial to acknowledge that HFMD prevalence continues to exhibit a distinct seasonal pattern and periodicity, and the occurrence of other EV infections poses a new challenge for children's health.

9.
Int J Pharm ; 661: 124474, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39019297

RESUMO

The aim of this study was to rapidly develop a sufficiently robust andrographolide nanosuspension (AG-NS) system using hummer acoustic resonance (HAR) technology. The system can effectively improve the dissolution properties of AG, while having high stability and scale-up adaptability. The formulation of AG-NS was optimized in a high-throughput manner using HAR technology and the preparation process was optimized stepwise. Optimal AG-NS with Z-Ave = 223.99 ± 3.16 nm, PDI=0.095 ± 0.007 and zeta potential = -33.20 ± 0.58 mV was successfully prepared with Polyvinylpyrrolidone K30 and Sodium dodecyl sulfate. The optimal prescription was successfully scaled up 100 and 150 times using HAR technology, which was the initial exploration of its commercial scale production. AG-NS was solidified using freeze drying and fluid bed technology, respectively. The optimal AG-NS and its solidified products were exhaustively characterized using various analytical techniques. The high energy input of HAR technology and drying process converted part of the drug into the amorphous state. The in-vitro drug dissolution studies demonstrated relatively higher drug dissolution for AG-NS and its solidified products compared to controls at both the dissolution media (pH 1.2 buffer and pH 6.8 buffer). AG-NS and its solidified products successfully maintained their physical stability in short-term stability and accelerated stability experiments, respectively.


Assuntos
Diterpenos , Liberação Controlada de Fármacos , Nanopartículas , Suspensões , Diterpenos/química , Nanopartículas/química , Estabilidade de Medicamentos , Liofilização , Solubilidade , Povidona/química , Tecnologia Farmacêutica/métodos , Composição de Medicamentos/métodos , Acústica , Tamanho da Partícula , Química Farmacêutica/métodos , Dodecilsulfato de Sódio/química
10.
Toxicol Appl Pharmacol ; 490: 117040, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39032800

RESUMO

Morphine is a widely used opioid for the treatment of pain. Differences in drug transporter expression and activity may contribute to variability in morphine pharmacokinetics and response. Using appropriate mouse models, we investigated the impact of the efflux transporters ABCB1 and ABCG2 and the OATP uptake transporters on the pharmacokinetics of morphine, morphine-3-glucuronide (M3G), and M6G. Upon subcutaneous administration of morphine, its plasma exposure in Abcb1a/1b-/-;Abcg2-/--, Abcb1a/1b-/-;Abcg2-/-;Oatp1a/1b-/-;Oatp2b1-/- (Bab12), and Oatp1a/1b-/-;Oatp2b1-/- mice was similar to that found in wild-type mice. Forty minutes after dosing, morphine brain accumulation increased by 2-fold when mouse (m)Abcb1 and mAbcg2 were ablated. Relative recovery of morphine in small intestinal content was significantly reduced in all the knockout strains. In the absence of mOatp1a/1b and mOatp2b1, plasma levels of M3G were markedly increased, suggesting a lower elimination rate. Moreover, Oatp-deficient mice displayed reduced hepatic and intestinal M3G accumulation. Mouse Oatps similarly affected plasma and tissue disposition of subcutaneously administered M6G. Human OATP1B1/1B3 transporters modestly contribute to the liver accumulation of M6G. In summary, mAbcb1, in combination with mAbcg2, limits morphine brain penetration and its net intestinal absorption. Variation in ABCB1 activity due to genetic polymorphisms/mutations and/or environmental factors might, therefore, partially affect morphine tissue exposure in patients. The ablation of mOatp1a/1b increases plasma exposure and decreases the liver and small intestinal disposition of M3G and M6G. Since the contribution of human OATP1B1/1B3 to M6G liver uptake was quite modest, the risks of undesirable drug interactions or interindividual variation related to OATP activity are likely negligible.


Assuntos
Camundongos Knockout , Derivados da Morfina , Morfina , Animais , Morfina/farmacocinética , Morfina/metabolismo , Derivados da Morfina/metabolismo , Derivados da Morfina/sangue , Camundongos , Distribuição Tecidual , Masculino , Encéfalo/metabolismo , Analgésicos Opioides/farmacocinética , Analgésicos Opioides/metabolismo , Analgésicos Opioides/sangue , Camundongos Endogâmicos C57BL , Transportadores de Ânions Orgânicos/metabolismo , Transportadores de Ânions Orgânicos/genética , Fígado/metabolismo , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética
11.
STAR Protoc ; 5(3): 103203, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39058588

RESUMO

Single-nuclei RNA sequencing (snRNA-seq) allows for obtaining gene expression profiles from frozen or hard-to-dissociate tissues at the single-nuclei level. Here, we describe a protocol to obtain snRNA-seq data of pancreatic tumors from orthotopically grafted organoid-derived mouse models. We provide details on the establishment of these mouse models, the isolation of single nuclei from pancreatic tumors, and the analysis of the snRNA-seq datasets. For complete details on the use and execution of this protocol, please refer to Mucciolo et al.1.

12.
Adv Mater ; 36(31): e2403551, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38837826

RESUMO

Conventional wound closure methods, including sutures and tissue adhesives, present significant challenges for self-care treatment, particularly in the context of bleeding wounds. Existing stimuli-responsive contractile materials designed for autonomous wound closure frequently lack sufficient output work density to generate the force needed to bring the wound edges into proximity or necessitate stimuli that are not compatible with the human body. Here, semi-transparent, flexible, and water-responsive shrinkable films, composed of poly(ethylene oxide) and α-cyclodextrin, are reported. These films exhibit remarkable stability under ambient conditions and demonstrate significant contraction (≈50%) within 6 s upon exposure to water, generating substantial contractile stress (up to 6 MPa) and output work density (≈1028 kJ m-3), which is 100 times larger than that of conventional hydrogel and 25 times larger than that of skeletal muscles. Remarkably, upon hydration, these films are capable of lifting objects 10 000 times their own weight. Leveraging this technology, water-shrink tapes, which, upon contact with water, effectively constrict human skin and autonomously close bleeding wounds in animal models within 10 seconds, are developed further. This work offers a novel approach to skin wound management, showing significant potential for emergency and self-care scenarios.


Assuntos
Polietilenoglicóis , Água , alfa-Ciclodextrinas , alfa-Ciclodextrinas/química , Polietilenoglicóis/química , Água/química , Humanos , Animais , Cicatrização/efeitos dos fármacos , Pele , Técnicas de Fechamento de Ferimentos
13.
Clin Neurol Neurosurg ; 243: 108389, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38870670

RESUMO

BACKGROUND: Hemorrhagic transformation (HT) is a common and serious complication in patients with acute ischemic stroke (AIS) after endovascular thrombectomy (EVT). This study was performed to determine the predictive factors associated with HT in stroke patients with EVT and to establish and validate a nomogram that combines with independent predictors to predict the probability of HT after EVT in patients with AIS. METHODS: All patients were randomly divided into development and validation cohorts at a ratio of 7:3. The least absolute shrinkage and selection operator (LASSO) regression was used to select the optimal factors, and multivariate logistic regression analysis was used to build a clinical prediction model. Calibration plots, decision curve analysis (DCA) and receiver operating characteristic curve (ROC) were generated to assess predictive performance. RESULTS: LASSO regression analysis showed that Alberta Stroke Program Early CT Scores (ASPECTS), international normalized ratio (INR), uric acid (UA), neutrophils (NEU) were the influencing factors for AIS with HT after EVT. A novel prognostic nomogram model was established to predict the possibility of HT with AIS after EVT. The calibration curve showed that the model had good consistency. The results of ROC analysis showed that the AUC of the prediction model established in this study for predicting HT was 0.797 in the development cohort and 0.786 in the validation cohort. CONCLUSION: This study proposes a novel and practical nomogram based on ASPECTS, INR, UA, NEU, which can well predict the probability of HT after EVT in patients with AIS.


Assuntos
Procedimentos Endovasculares , AVC Isquêmico , Nomogramas , Trombectomia , Humanos , AVC Isquêmico/cirurgia , AVC Isquêmico/diagnóstico por imagem , Masculino , Trombectomia/métodos , Feminino , Idoso , Procedimentos Endovasculares/métodos , Procedimentos Endovasculares/efeitos adversos , Pessoa de Meia-Idade , Modelos Logísticos , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/cirurgia , Idoso de 80 Anos ou mais , Hemorragias Intracranianas/etiologia , Hemorragias Intracranianas/diagnóstico por imagem
14.
Fitoterapia ; 177: 106090, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38906388

RESUMO

A chemical investigation of the aerial parts of Piper sarmentosum resulted in the isolation and identification of 14 amide alkaloids, including three new amide alkaloids, pipersarmenoids A - C (1-3), three new natural amide alkaloids, pipersarmenoids D - F (4-6), and 8 known analogues, N-p-coumaroyltyramine (7), piperlotine C (8), piperlotine D (9), pellitorine (10), sarmentine (11), aurantiamide acetate (12), 1-cinnamoyl pyrrolidine (13) and sarmentamide B (14). Their structures were determined by spectroscopic analysis including HRESIMS and 1D and 2D NMR. The cytotoxicity, neuroinflammation-inhibiting and acetylcholinesterase (AChE) inhibitory activities of those compounds were tested. Compounds 1, 2 and 12 inhibited NO production induced by LPS in BV2 cells with IC50 values of 9.36, 12.53 and 10.77 µM, respectively. Moreover, 1, 2, 7 and 11 showed moderate inhibitory activity on AChE with IC50 values ranging from 37.56 to 48.84 µM.


Assuntos
Alcaloides , Inibidores da Colinesterase , Compostos Fitoquímicos , Piper , Componentes Aéreos da Planta , Alcaloides/farmacologia , Alcaloides/isolamento & purificação , Alcaloides/química , Piper/química , Estrutura Molecular , Animais , Camundongos , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/isolamento & purificação , Componentes Aéreos da Planta/química , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Linhagem Celular , Amidas/farmacologia , Amidas/isolamento & purificação , Amidas/química , Óxido Nítrico/metabolismo , China , Microglia/efeitos dos fármacos , Ácidos Graxos Insaturados , Alcamidas Poli-Insaturadas
15.
J Pharm Biomed Anal ; 248: 116313, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-38878453

RESUMO

Hypericum perforatum L. (HPL), also known as St. John's wort, is one of the extensively researched domestically and internationally as a medicinal plant. In this study, non-targeted metabolomics combined with machine learning methods were used to identify reasonable quality indicators for the holistic quality control of HPL. First, the high-resolution MS data from different samples of HPL were collected, and visualized the chemical compounds through the MS molecular network. A total of 122 compounds were identified. Then, the orthogonal partial least squares-discriminant analysis (OPLS-DA) model was established for comparing the differences in metabolite expression between flower, leaf, and branches. A total of 46 differential metabolites were screened out. Subsequently, analyzing the pharmacological activities of these differential metabolites based on protein-protein interaction (PPI) network. A total of 25 compounds associated with 473 gene targets were retrieved. Among them, 13 highly active compounds were selected as potential quality markers, and five compounds were ultimately selected as quality control markers for HPL. Finally, three different classifiers (support vector machine (SVM), random forest (RF), and K-nearest neighbor (KNN)) were used to validate whether the selected quality control markers are qualified. When the feature count is set to 122 and 46, the RF model demonstrates optimal performance. As the number of variables decreases, the performance of the RF model degrades. The KNN model and the SVM model also exhibit a decrease in performance but still manage to satisfy the intended requirements. The strategy can be applied to the quality control of HPL and can provide a reference for the quality control of other herbal medicines.


Assuntos
Hypericum , Aprendizado de Máquina , Metabolômica , Controle de Qualidade , Espectrometria de Massas em Tandem , Hypericum/química , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida de Alta Pressão/métodos , Metabolômica/métodos , Máquina de Vetores de Suporte , Extratos Vegetais/química , Extratos Vegetais/análise , Análise dos Mínimos Quadrados , Mapas de Interação de Proteínas/efeitos dos fármacos , Análise Discriminante , Plantas Medicinais/química
16.
Inflamm Res ; 73(8): 1393-1409, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38896289

RESUMO

BACKGROUND: Tumor microenvironment (TME) heterogeneity is an important factor affecting the treatment response of immune checkpoint inhibitors (ICI). However, the TME heterogeneity of melanoma is still widely characterized. METHODS: We downloaded the single-cell sequencing data sets of two melanoma patients from the GEO database, and used the "Scissor" algorithm and the "BayesPrism" algorithm to comprehensively analyze the characteristics of microenvironment cells based on single-cell and bulk RNA-seq data. The prediction model of immunotherapy response was constructed by machine learning and verified in three cohorts of GEO database. RESULTS: We identified seven cell types. In the Scissor+ subtype cell population, the top three were T cells, B cells and melanoma cells. In the Scissor- subtype, there are more macrophages. By quantifying the characteristics of TME, significant differences in B cells between responders and non-responders were observed. The higher the proportion of B cells, the better the prognosis. At the same time, macrophages in the non-responsive group increased significantly. Finally, nine gene features for predicting ICI response were constructed, and their predictive performance was superior in three external validation groups. CONCLUSION: Our study revealed the heterogeneity of melanoma TME and found a new predictive biomarker, which provided theoretical support and new insights for precise immunotherapy of melanoma patients.


Assuntos
Imunoterapia , Melanoma , Análise de Sequência de RNA , Análise de Célula Única , Microambiente Tumoral , Humanos , Microambiente Tumoral/imunologia , Melanoma/genética , Melanoma/terapia , Melanoma/imunologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Aprendizado de Máquina , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/terapia , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/tratamento farmacológico , Prognóstico , Linfócitos B/imunologia
17.
Nature ; 630(8015): 84-90, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38840015

RESUMO

Direct and precise monitoring of intracranial physiology holds immense importance in delineating injuries, prognostication and averting disease1. Wired clinical instruments that use percutaneous leads are accurate but are susceptible to infection, patient mobility constraints and potential surgical complications during removal2. Wireless implantable devices provide greater operational freedom but include issues such as limited detection range, poor degradation and difficulty in size reduction in the human body3. Here we present an injectable, bioresorbable and wireless metastructured hydrogel (metagel) sensor for ultrasonic monitoring of intracranial signals. The metagel sensors are cubes 2 × 2 × 2 mm3 in size that encompass both biodegradable and stimulus-responsive hydrogels and periodically aligned air columns with a specific acoustic reflection spectrum. Implanted into intracranial space with a puncture needle, the metagel deforms in response to physiological environmental changes, causing peak frequency shifts of reflected ultrasound waves that can be wirelessly measured by an external ultrasound probe. The metagel sensor can independently detect intracranial pressure, temperature, pH and flow rate, realize a detection depth of 10 cm and almost fully degrade within 18 weeks. Animal experiments on rats and pigs indicate promising multiparametric sensing performances on a par with conventional non-resorbable wired clinical benchmarks.


Assuntos
Implantes Absorvíveis , Encéfalo , Hidrogéis , Monitorização Fisiológica , Ondas Ultrassônicas , Tecnologia sem Fio , Animais , Masculino , Ratos , Encéfalo/fisiologia , Hidrogéis/química , Concentração de Íons de Hidrogênio , Injeções/instrumentação , Pressão Intracraniana , Monitorização Fisiológica/instrumentação , Monitorização Fisiológica/métodos , Ratos Sprague-Dawley , Porco Miniatura , Temperatura , Fatores de Tempo , Tecnologia sem Fio/instrumentação
18.
J Am Chem Soc ; 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38858162

RESUMO

Understanding how life's essential homochiral biopolymers arose from racemic precursors is a challenging quest. Herein, we present a groundbreaking approach involving hierarchical chiral assembly-driven stereoselective ring-opening polymerization of ε-benzyloxycarbonyl-l/d-lysine N-carboxyanhydrides assisted by ultrasonication in an aqueous medium. This method enabled a narrow dispersity within a few minutes and the achievement of high molecular weight for polypeptides, employing a living polymerization mechanism. The polymerization of l and d enantiomers yielded predominantly right- and left-handed superhelical assemblies in a one-pot preparation, respectively. Notably, stereoselective polypeptide segments were efficiently prepared through hierarchical assembly-driven polymerization of racemic monomers in the absence of a catalyst. This research offers an innovative strategy for the convenient preparations of stereoenriched polypeptides and, more importantly, sheds light on the plausible emergence of homochiral peptides in the origin of life.

19.
Fundam Res ; 4(2): 291-299, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38933506

RESUMO

The photogenerated charge carrier separation and transportation of inside photocathodes can greatly influence the performance of photoelectrochemical (PEC) H2 production devices. Coupling TiO2 with p-type semiconductors to construct heterojunction structures is one of the most widely used strategies to facilitate charge separation and transportation. However, the band position of TiO2 could not perfectly match with all p-type semiconductors. Here, taking antimony selenide (Sb2Se3) as an example, a rational strategy was developed by introducing a viologen electron transfer mediator (ETM) containing polymeric film (poly-1,1'-dially-[4,4'-bipyridine]-1,1'-diium, denoted as PV2+) at the interface between Sb2Se3 and TiO2 to regulate the energy band alignment, which could inhibit the recombination of photogenerated charge carriers of interfaces. With Pt as a catalyst, the constructed Sb2Se3/PV2+/TiO2/Pt photocathode showed a superior PEC hydrogen generation activity with a photocurrent density of -18.6 mA cm-2 vs. a reversible hydrogen electrode (RHE) and a half-cell solar-to-hydrogen efficiency (HC-STH) of 1.54% at 0.17 V vs. RHE, which was much better than that of the related Sb2Se3/TiO2/Pt photocathode without PV2+ (-9.8 mA cm-2, 0.51% at 0.10 V vs. RHE).

20.
Spectrochim Acta A Mol Biomol Spectrosc ; 320: 124590, 2024 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-38850827

RESUMO

A data fusion strategy based on near-infrared (NIR) and mid-infrared (MIR) spectroscopy techniques were developed for rapid origin identification and quality evaluation of Lonicerae japonicae flos (LJF). A high-level data fusion for origin identification was formed using the soft voting method. This data fusion model achieved accuracy, log-loss value and Kappa value of 95.5%, 0.347 and 0.910 on the prediction set. The spectral data were converted to liquid chromatography data using a data fusion model constructed by the weighted average algorithm. The Euclidean distance and adjusted cosine similarity were used to evaluate the similarity between the converted and the real chromatographic data, with results of 247.990 and 0.996, respectively. The data fusion models all performed better than the models constructed using single data. This indicates that multispectral data fusion techniques have a wide range of application prospects and practical value in the quality control of natural products such as LJF.


Assuntos
Lonicera , Espectroscopia de Luz Próxima ao Infravermelho , Lonicera/química , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Espectrofotometria Infravermelho/métodos , Controle de Qualidade , Algoritmos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/análise , Extratos Vegetais
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