RESUMEN

In 2023, the U.S. Food and Drug Administration has approved 29 small molecule drugs. These newly approved small molecule drugs possess the distinct scaffolds, thereby exhibiting diverse mechanisms of action and binding modalities. Moreover, the marketed drugs have always been an important source of new drug development and creative inspiration, thereby fostering analogous endeavors in drug discovery that potentially extend to the diverse clinical indications. Therefore, conducting a comprehensive evaluation of drug approval experience and associated information will facilitate the expedited identification of highly potent drug molecules. In this review, we comprehensively summarized the relevant information regarding the clinical applications, mechanisms of action and chemical synthesis of 29 small molecule drugs, with the aim of providing a promising structural basis and design inspiration for pharmaceutical chemists.

Asunto(s)

Aprobación de Drogas , United States Food and Drug Administration , Estados Unidos , Humanos , Preparaciones Farmacéuticas/síntesis química , Preparaciones Farmacéuticas/química , Descubrimiento de Drogas , Bibliotecas de Moléculas Pequeñas/síntesis química

RESUMEN

BACKGROUND: The tumor microenvironment (TME) exerts profound effects on tumor progression and therapeutic efficacy. In hepatocellular carcinoma (HCC), the TME is enriched with cancer-associated fibroblasts (CAFs), which secrete a plethora of cytokines, chemokines, and growth factors that facilitate tumor cell proliferation and invasion. However, the intricate architecture of the TME in HCC, as well as the mechanisms driving interactions between tumor cells and CAFs, remains largely enigmatic. METHODS: We analyzed 10 spatial transcriptomics and 12 single-cell transcriptomics samples sourced from public databases, complemented by 20 tumor tissue samples from liver cancer patients obtained in a clinical setting. RESULTS: Our findings reveal that tumor cells exhibiting high levels of SPP1 are preferentially localized adjacent to hepatic stellate cells (HSCs). The SPP1 secreted by these tumor cells interacts with the CD44 receptor on HSCs, thereby activating the PI3K/AKT signaling pathway, which promotes the differentiation of HSCs into CAFs. Notably, blockade of the CD44 receptor effectively abrogates this interaction. Furthermore, in vivo studies demonstrate that silencing SPP1 expression in tumor cells significantly impairs HSC differentiation into CAFs, leading to a reduction in tumor volume and collagen deposition within the tumor stroma. CONCLUSIONS: This study delineates the SPP1-CD44 signaling axis as a pivotal mechanism underpinning the interaction between tumor cells and CAFs. Targeting this pathway holds potential to mitigate liver fibrosis and offers novel therapeutic perspectives for liver cancer management.

Asunto(s)

Carcinoma Hepatocelular , Quimiotaxis , Células Estrelladas Hepáticas , Neoplasias Hepáticas , Transcriptoma , Microambiente Tumoral , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Humanos , Transcriptoma/genética , Células Estrelladas Hepáticas/metabolismo , Células Estrelladas Hepáticas/patología , Animales , Quimiotaxis/genética , Fibroblastos/metabolismo , Fibroblastos/patología , Línea Celular Tumoral , Transducción de Señal , Receptores de Hialuranos/metabolismo , Fibroblastos Asociados al Cáncer/metabolismo , Fibroblastos Asociados al Cáncer/patología , Diferenciación Celular , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Regulación Neoplásica de la Expresión Génica

RESUMEN

BACKGROUND/AIMS: Gastric cancer (GC) ranks among the prevalent types of cancer, and its progression is influenced by the tumor microenvironment (TME). A comprehensive comprehension of the TME associated with GC has the potential to unveil therapeutic targets of significance. METHODS: The complexity and heterogeneity of TME interactions were revealed through our investigation using an integrated analysis of single-cell and bulk-tissue sequencing data. RESULTS: We constructed a single-cell transcriptomic atlas of 150,913 cells isolated from GC patients. Our analysis revealed the intricate nature and heterogeneity of the GC TME and the metabolic properties of major cell types. Furthermore, two cell subtypes, LOX+ Fibroblasts and M2 Macrophages, were enriched in tumor tissue and related to the outcome of GC patients. In addition, LOX+ Fibroblasts were significantly associated with M2 macrophages. immunofluorescence double labeling indicated LOX+ Fibroblasts and M2 Macrophages were tightly localized in GC tissue. The two cell subpopulations strongly interacted in a hypoxic microenvironment, yielding an immunosuppressive phenotype. Our findings further suggest that LOX+ Fibroblasts may act as a trigger for inducing the differentiation of monocytes into M2 Macrophages via the IL6-IL6R signaling pathway. CONCLUSIONS: Our study revealed the intricate and interdependent communication network between the fibroblast and macrophage subpopulations, which could offer valuable insights for targeted manipulation of the tumor microenvironment.

Asunto(s)

Fibroblastos , Macrófagos , Análisis de la Célula Individual , Neoplasias Gástricas , Microambiente Tumoral , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Neoplasias Gástricas/metabolismo , Humanos , Microambiente Tumoral/inmunología , Análisis de la Célula Individual/métodos , Macrófagos/metabolismo , Macrófagos/inmunología , Fibroblastos/metabolismo , Fibroblastos/patología , Receptores Depuradores de Clase E/metabolismo , Receptores Depuradores de Clase E/genética , Comunicación Celular/inmunología , Proteína-Lisina 6-Oxidasa/metabolismo , Proteína-Lisina 6-Oxidasa/genética , Fibroblastos Asociados al Cáncer/metabolismo , Fibroblastos Asociados al Cáncer/patología , Transcriptoma , Transducción de Señal

RESUMEN

Objective: The aim of this study was to evaluate the effectiveness of burosumab therapy in children with X-Linked Hypophosphatemia (XLH). Materials and methods: We systematically reviewed literature from PubMed, Web of Science, The Cochrane Library, and Embase up until January 2024, using EndNote Web for study organization. The Newcastle-Ottawa scale guided quality assessment, while Revman software was used for data analysis and visualization. Study selection, quality evaluation, and data aggregation were independently performed by three researchers. Results: The meta-analysis encompassed ten studies, including eight cohort studies that examined burosumab's impact pre- and post-administration, and two randomized controlled trials comparing burosumab to standard therapy. The evidence from this review suggests burosumab's superiority in managing XLH in pediatric populations, particularly in improving key biochemical markers including 1,25-dihydroxyvitamin D (1,25-(OH)2D), phosphorus, and alkaline phosphatase (ALP), alongside improvements in the renal tubular maximum reabsorption rate of phosphate to glomerular filtration rate (TmP/GFR), and significant skeletal improvements as indicated by the rickets severity score (RSS) and the 6-minute walk test (6MWT). However, the long-term safety and effects, including height and quality of life (QOL) data, remains to be elucidated. Conclusions: Burosumab has shown significant therapeutic effectiveness in treating children with XLH, highlighting its potential as a key treatment option.

Asunto(s)

Anticuerpos Monoclonales Humanizados , Raquitismo Hipofosfatémico Familiar , Humanos , Raquitismo Hipofosfatémico Familiar/tratamiento farmacológico , Niño , Anticuerpos Monoclonales Humanizados/uso terapéutico , Resultado del Tratamiento

RESUMEN

Periodontitis, with its persistent nature, causes significant distress for most sufferers. Current treatments, such as mechanical cleaning and surgery, often fail to fully address the underlying overactivation of fibroblasts that drives this degradation. Targeting the post-transcriptional regulation of fibroblasts, particularly at the 3'-untranslated regions (3'UTR) of pathogenic genes, offers a therapeutic strategy for periodontitis. Herein, we developed a DNA nanorobot for this purpose. This system uses a dynamic DNA nanoframework to incorporate therapeutic microRNAs through molecular recognition and covalent bonds, facilitated by DNA monomers modified with disulfide bonds. The assembled-DNA nanoframework is encapsulated in a cell membrane embedded with a fibroblast-targeting peptide. By analyzing the 3'UTR regions of pathogenic fibroblast genes FOSB and JUND, we identified the therapeutic microRNA as miR-1-3p and integrated it into this system. As expected, the DNA nanorobot delivered the internal components to fibroblasts by the targeting peptide and outer membrane that responsively releases miR-1-3p under intracellular glutathione. It resulted in a precise reduction of mRNA and suppression of protein function in pathogenic genes, effectively reprogramming fibroblast behavior. Our results confirm that this approach not only mitigates the inflammation but also promotes tissue regeneration in periodontal models, offering a promising therapeutic avenue for periodontitis.

Asunto(s)

Regiones no Traducidas 3' , ADN , Fibroblastos , MicroARNs , Periodontitis , Periodontitis/genética , Periodontitis/patología , Fibroblastos/metabolismo , Regiones no Traducidas 3'/genética , ADN/química , ADN/genética , MicroARNs/genética , MicroARNs/metabolismo , Humanos , Animales , Ratones

RESUMEN

In 2022, the U.S. Food and Drug Administration approved a total of 16 marketing applications for small molecule drugs, which not only provided dominant scaffolds but also introduced novel mechanisms of action and clinical indications. The successful cases provide valuable information for optimizing efficacy and enhancing pharmacokinetic properties through strategies like macrocyclization, bioequivalent group utilization, prodrug synthesis, and conformation restriction. Therefore, gaining an in-depth understanding of the design principles and strategies underlying these drugs will greatly facilitate the development of new therapeutic agents. This review focuses on the research and development process of these newly approved small molecule drugs including drug design, structural modification, and improvement of pharmacokinetic properties to inspire future research in this field.

Asunto(s)

Aprobación de Drogas , United States Food and Drug Administration , Estados Unidos , Humanos , Bibliotecas de Moléculas Pequeñas/química , Bibliotecas de Moléculas Pequeñas/farmacología , Bibliotecas de Moléculas Pequeñas/síntesis química , Diseño de Fármacos , Estructura Molecular

Asunto(s)

Encéfalo , Curcumina , Factor 2 Relacionado con NF-E2 , Animales , Curcumina/farmacología , Factor 2 Relacionado con NF-E2/metabolismo , Factor 2 Relacionado con NF-E2/genética , Ratas , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Masculino , Ratas Sprague-Dawley , Explosiones , Enfermedades Neuroinflamatorias/metabolismo , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Hemo-Oxigenasa 1/metabolismo , Hemo-Oxigenasa 1/genética , Traumatismos por Explosión/metabolismo , Transducción de Señal/efectos de los fármacos , Hemo Oxigenasa (Desciclizante)/metabolismo , Antiinflamatorios no Esteroideos/farmacología

RESUMEN

Chemotherapies are commonly used in cancer therapy, their applications are limited to low specificity, severe adverse reactions, and long-term medication-induced drug resistance. Poly(ADP-ribose) polymerase (PARP) inhibitors are a novel class of antitumor drugs developed to solve these intractable problems based on the mechanism of DNA damage repair, which have been widely applied in the treatment of ovarian cancer, breast cancer, and other cancers through inducing synthetic lethal effect and trapping PARP-DNA complex in BRCA gene mutated cancer cells. In recent years, PARP inhibitors have been widely used in combination with various first-line chemotherapy drugs, targeted drugs and immune checkpoint inhibitors to expand the scope of clinical application. However, the intricate mechanisms underlying the drug resistance to PARP inhibitors, including the restoration of homologous recombination, stabilization of DNA replication forks, overexpression of drug efflux protein, and epigenetic modifications pose great challenges and desirability in the development of novel PARP inhibitors. In this review, we will focus on the mechanism, structure-activity relationship, and multidrug resistance associated with the representative PARP inhibitors. Furthermore, we aim to provide insights into the development prospects and emerging trends to offer guidance for the clinical application and inspiration for the development of novel PARP inhibitors and degraders.

RESUMEN

In 2023, the U.S. Food and Drug Administration has approved 55 novel medications, consisting of 17 biologics license applications and 38 new molecular entities. Although the biologics license applications including antibody and enzyme replacement therapy set a historical record, the new molecular entities comprising small molecule drugs, diagnostic agent, RNA interference therapy and biomacromolecular peptide still account for over 50 % of the newly approved medications. The novel and privileged scaffolds derived from drugs, active molecules and natural products are consistently associated with the discovery of new mechanisms, the expansion of clinical indications and the reduction of side effects. Moreover, the structural modifications based on the promising scaffolds can provide the clinical candidates with the improved biological activities, bypass the patent protection and greatly shorten the period of new drug discovery. Therefore, conducting an appraisal of drug approval experience and related information will expedite the identification of more potent drug molecules. In this review, we comprehensively summarized the pertinent information encompassing the clinical application, mechanism, elegant design and development processes of 28 small molecule drugs, and expected to provide the promising structural basis and design inspiration for pharmaceutical chemists.

Asunto(s)

Aprobación de Drogas , United States Food and Drug Administration , Humanos , Estados Unidos , Bibliotecas de Moléculas Pequeñas/química , Bibliotecas de Moléculas Pequeñas/farmacología , Estructura Molecular

RESUMEN

Background: The RESORCE-III trial demonstrated that advanced hepatocellular carcinoma (HCC) patients who progressed on sorafenib and had second-line therapy with regorafenib improved overall survival compared with placebo. Later, immunotherapy with immune checkpoint inhibitors (ICIs) combined with antiangiogenetic antibodies has evolved as the preferred first-line treatment for fit patients. We aimed to explore the efficacy and safety of regorafenib as a first-line agent alone or in combination with ICIs in patients with advanced HCC. Methods: We identified 50 patients with advanced HCC treated with regorafenib as a first-line agent. Two patients were lost to follow-up and excluded. Baseline factors, dosing, concomitant use of ICIs, toxicity and outcome of treatment were recorded from electronic medical records. Results: Twenty-six patients received regorafenib as monotherapy and twenty-two received regorafenib + ICI in combination. In the total cohort, the median progression-free survival (mPFS) was 7.7 months and the median overall survival (mOS) was 16.7 months (P=0.02). Objective response rate (ORR) and disease control rate (DCR) assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 were 21% and 73%. In the regorafenib monotherapy group, mPFS was 5.9 months, and mOS was 13.9 months; in the combination group, mPFS was 7.8 months, and mOS was 23.6 months. ORR and DCR were 15% and 65% in the monotherapy group, and 27% and 82% in the combined treatment group, respectively. Conclusions: Regorafenib used in combination with ICIs had a mild safety profile and resulted in improved response and an almost doubling of mOS compared to monotherapy, warranting further prospective evaluation in a randomized study.

RESUMEN

Objective: To compare the effects of metaraminol and norepinephrine on hemodynamics and kidney injury in the treatment of septic shock, and calculate the conversion dose ratio between the two vasopressors. Methods: This randomized controlled study was performed on 15 Guizhou miniature pigs. Septic shock was induced by fecal peritonitis in 10 animals, and 5 were used as a sham-operated group (shams). Fluid resuscitation and vasopressors were initiated 30 min after the onset of septic shock. The septic shock pigs were randomly assigned to receive one of the two drugs to restore and maintain mean arterial pressure (MAP) ≥ 65 mmHg for 3 h. Hemodynamics and heart rate were continuously monitored. Results: There was no significant difference in MAP, heart rate, cardiac output (CO) and central venous pressure (CVP) between the two groups after treatment. No arrhythmias such as atrial fibrillation and ventricular fibrillation presented during continuous monitoring. After septic shock, the animals showed obvious kidney injury. In addition, compared with norepinephrine, the creatinine at 3 h was significantly lower with metaraminol. According to propensity score matching, the ratio of 6: 1 was considered appropriate for the dose equivalence calculation of metaraminol (µg·kg-1·min-1): norepinephrine (µg·kg-1·min-1). Conclusion: Metaraminol has a similar pressor effect to norepinephrine in septic shock; it does not increase heart rate and aggravate kidney injury after shock compared with norepinephrine. And our research may provide some laboratory evidence for the clinical usage of metaraminol.

RESUMEN

As a comprehensive secondary prevention program, cardiac rehabilitation (CR) is a beneficial and cost-effective intervention for patients with heart disease, but the participation rate of patients in CR is low globally. In recent years, due to the COVID-19 pandemic and scientific and technological advances, an increasing number of alternative CR modes have been developed, such as remote CR, home-based CR, hybrid CR and virtual CR. These alternative CR modes represent changes and new opportunities for patients with heart disease. In this review, we will discuss in detail the impact of CR on patients with different types of heart disease, review the various alternative CR models, and explore some prospects for the future of CR in the field of heart disease.

RESUMEN

OBJECTIVE: This study aims to develop a compound biomaterial to achieve effective soft tissue regeneration. METHODOLOGY: Compound hyaluronic acid (CHA) and liquid horizontal-platelet-rich fibrin (H-PRF) were mixed at a ratio of 1:1 to form a CHA-PRF gel. Human gingival fibroblasts (HGFs) were used in this study. The effect of CHA, H-PRF, and the CHA-PRF gel on cell viability was evaluated by CCK-8 assays. Then, the effect of CHA, H-PRF, and the CHA-PRF gel on collagen formation and deposition was evaluated by qRT‒PCR and immunofluorescence analysis. Finally, qRT‒PCR, immunofluorescence analysis, Transwell assays, and scratch wound-healing assays were performed to determine how CHA, H-PRF, and the CHA-PRF gel affect the migration of HGFs. RESULTS: The combination of CHA and H-PRF shortened the coagulation time of liquid H-PRF. Compared to the pure CHA and H-PRF group, the CHA-PRF group exhibited the highest cell proliferation at all time points, as shown by the CCK-8 assay. Col1a and FAK were expressed at the highest levels in the CHA-PRF group, as shown by qRT‒PCR. CHA and PRF could stimulate collagen formation and HGF migration, as observed by fluorescence microscopy analysis of COL1 and F-actin and Transwell and scratch healing assays. CONCLUSION: The CHA-PRF group exhibited greater potential to promote soft tissue regeneration by inducing cell proliferation, collagen synthesis, and migration in HGFs than the pure CHA or H-PRF group. CHA-PRF can serve as a great candidate for use alone or in combination with autografts in periodontal or peri-implant soft tissue regeneration.

Asunto(s)

Movimiento Celular , Proliferación Celular , Supervivencia Celular , Fibroblastos , Encía , Ácido Hialurónico , Fibrina Rica en Plaquetas , Regeneración , Ácido Hialurónico/farmacología , Humanos , Fibroblastos/efectos de los fármacos , Encía/efectos de los fármacos , Encía/citología , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Regeneración/efectos de los fármacos , Factores de Tiempo , Movimiento Celular/efectos de los fármacos , Reproducibilidad de los Resultados , Técnica del Anticuerpo Fluorescente , Reacción en Cadena en Tiempo Real de la Polimerasa , Colágeno , Ensayo de Materiales , Cicatrización de Heridas/efectos de los fármacos , Materiales Biocompatibles/farmacología , Colágeno Tipo I/análisis

RESUMEN

The rising sentiment challenges of the metropolitan residents may be attributed to the extreme temperatures. However, nationwide real-time empirical studies that examine this claim are rare. In this research, we construct a daily extreme temperature index and sentiment metric using geotagged posts on one of China's largest social media sites, Weibo, to verify this hypothesis. We find that extreme temperatures causally decrease individuals' sentiment, and extremely low temperature may decrease more than extremely high temperature. Heterogeneity analyses reveal that individuals living in high levels of PM2.5, existing new COVID-19 diagnoses and low-disposable income cities on workdays are more vulnerable to the impact of extreme temperatures on sentiment. More importantly, the results also demonstrate that the adverse effects of extremely low temperatures on sentiment are more minor for people living in northern cities with breezes. Finally, we estimate that with a one-standard increase of extremely high (low) temperature, the sentiment decreases by approximately 0.161 (0.272) units. Employing social media to monitor public sentiment can assist policymakers in developing data-driven and evidence-based policies to alleviate the adverse impacts of extreme temperatures.

Asunto(s)

COVID-19 , Ciudades , Medios de Comunicación Sociales , China , Humanos , COVID-19/epidemiología , COVID-19/psicología , SARS-CoV-2/aislamiento & purificación , Opinión Pública , Temperatura

RESUMEN

Tracking the variation of Cl- timely within the crevice is of great significance for comprehending the dynamic mechanism of crevice corrosion. The reported chloride ion selective electrodes are difficult to realize the long-time Cl- detection inside the confined crevice, due to their millimeter size or a relative limited lifespan. For this purpose, an Ag/AgCl ultra-micro sensor (UMS) with a radius of 12.5 µm was fabricated and optimized using laser drawing and electrodeposition techniques. Results show the AgCl film's structure is significantly impacted by the deposited current density, and further affects the linear response, life span and stability of Ag/AgCl UMS. The UMS prepared at current density of 0.1 mA/cm2 for 2 h shows a rapid response (several seconds), excellent stability and reproducibility, strong acid/alkali tolerance, sufficient linearity (R2 > 0.99), and long lifespan (86 days). Moreover, combined with the potentiometric mode of scanning electrochemical microscope (SECM), the Ag/AgCl UMS was successfully applied to monitor the in-situ radial Cl- concentration in micro-regions inside a 100 µm gap of stainless steel. The findings demonstrated that there was obvious radial difference in Cl- concentration inside the crevice, where the fastest rise in Cl- concentration was at the opening. The proposed method which combines the UMS with SECM has attractive practical applications for microzone Cl- monitoring in real time inside crevice. It may further promote the study of other localized corrosion mechanism and the development of microzone ions detection method.

RESUMEN

PURPOSE: Establishment of sister chromatid cohesion N-acetyltransferase 2 (ESCO2) is involved in the mitotic S-phase adhesins acetylation and is responsible for bridging two sister chromatids. However, present ESCO2 cancer research is limited to a few cancers. No systematic pan-cancer analysis has been conducted to investigate its role in diagnosis, prognosis, and effector function. METHODS: We thoroughly examined the ESCO2 carcinogenesis in pan-cancer by combining public databases such as The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression Project (GTEx), UALCAN and Tumor Immune Single-cell Hub (TISCH). The analysis includes differential expression analysis, survival analysis, cellular effector function, gene mutation, single cell analysis, and tumor immune cell infiltration. Furthermore, we confirmed ESCO2's impacts on clear cell renal cell carcinoma (ccRCC) cells' proliferative and invasive capacities in vitro. RESULTS: In our study, 30 of 33 cancer types exhibited considerably greater levels of ESCO2 expression in tumor tissue using TCGA and GTEx databases, whereas acute myeloid leukemia (LAML) exhibited significantly lower levels. Kaplan-Meier survival analyses in adrenocortical carcinoma (ACC), kidney chromophobe (KICH), kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), brain lower grade glioma (LGG), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), mesothelioma (MESO), and pancreatic adenocarcinoma (PAAD) demonstrated that tumor patients with high ESCO2 expression have short survival periods. However, in thymoma (THYM), colon adenocarcinoma (COAD) and rectum adenocarcinoma (READ), ESCO2 was a favorable prognostic factor. Moreover, ESCO2 expression positively correlates with tumor stage and tumor size in several cancers, including LIHC, KIRC, KIRP and LUAD. Function analysis revealed that ESCO2 participates in mitosis, cell cycle, DNA damage repair, and other processes. CDK1 was identified as a downstream gene regulated by ESCO2. Furthermore, ESCO2 might also be implicated in immune cell infiltration. Finally, ESCO2'S knockdown significantly inhibited the A498 and T24 cells' proliferation, invasion, and migration. CONCLUSIONS: In conclusion, ESCO2 is a possible pan-cancer biomarker and oncogene that can reliably predict the prognosis of cancer patients. ESCO2 was also implicated in the cell cycle and proliferation regulation. In a nutshell, ESCO2 is a therapeutically viable and dependable target.

Asunto(s)

Acetiltransferasas , Adenocarcinoma , Proteínas Cromosómicas no Histona , Neoplasias del Colon , Humanos , Adenocarcinoma del Pulmón , Neoplasias de la Corteza Suprarrenal , Carcinoma Hepatocelular , Carcinoma de Células Renales/genética , Neoplasias Renales , Neoplasias Hepáticas , Neoplasias Pulmonares , Neoplasias Pancreáticas , Neoplasias del Timo

RESUMEN

To study the heavy metal accumulation and its impact on insect exterior and chromosome morphology, and reveal the molecular mechanism of insects adapting to long-term heavy metal compound pollution habitats, this study, in the Diaojiang river basin, which has been polluted by heavy metals(HMs) for nearly a thousand years, two Eucriotettix oculatus populations was collected from mining and non-mining areas. It was found that the contents of 7 heavy metals (As, Cd, Pb, Zn, Cu, Sn, Sb) in E. oculatus of the mining area were higher than that in the non-mining 1-11 times. The analysis of morphology shows that the external morphology, the hind wing type and the chromosomal morphology of E. oculatus are significant differences between the two populations. Based on the heavy metal accumulation，morphological change, and stable population density, it is inferred that the mining area population has been affected by heavy metals and has adapted to the environment of heavy metals pollution. Then, by analyzing the transcriptome of the two populations, it was found that the digestion, immunity, excretion, endocrine, nerve, circulation, reproductive and other systems and lysosomes, endoplasmic reticulum and other cell structure-related gene expression were suppressed. This shows that the functions of the above-mentioned related systems of E. oculatus are inhibited by heavy metal stress. However, it has also been found that through the significant up-regulation of genes related to the above system, such as ATP2B, pepsin A, ubiquitin, AQP1, ACOX, ATPeV0A, SEC61A, CANX, ALDH7A1, DLD, aceE, Hsp40, and catalase, etc., and the down-regulation of MAPK signalling pathway genes, can enhanced nutrient absorption, improve energy metabolism, repair damaged cells and degrade abnormal proteins, maintain the stability of cells and systems, and resist heavy metal damage so that E. oculatus can adapt to the environment of heavy metal pollution for a long time.

Asunto(s)

Saltamontes , Metales Pesados , Contaminantes Químicos del Agua , Animales , Metales Pesados/toxicidad , Contaminantes Químicos del Agua/toxicidad , Saltamontes/efectos de los fármacos , Saltamontes/anatomía & histología , Monitoreo del Ambiente/métodos , Minería , China , Adaptación Fisiológica/efectos de los fármacos , Transcriptoma/efectos de los fármacos , Ríos/química

RESUMEN

OBJECTIVE: To study the etiological characteristics of community-acquired pneumonia (CAP) combined with type 2 diabetes (T2D), providing a reference for early clinical diagnosis and treatment of the disease. METHODS: We selected a total of 93 patients with CAP and analyzed their metagenomics nextgeneration sequencing (mNGS) data. The case group comprised 46 patients with combined CAP/T2D, and the control group comprised 47 patients without diabetes. We analyzed the pathogenic findings of the two groups. RESULTS: There were statistically significant differences in age between the two groups (P = 0.001). Leukocytes (P = 0.012), blood platelets (P = 0.034), fibrinogen (P = 0.037), D-dimer (P = 0.000), calcitonin ogen (P = 0.015), ultrasensitive C-reactive protein or C-reactive protein (CRP) (P = 0.000), serum amyloid A (P = 0.000), and erythrocyte sedimentation rate (P = 0.003) were higher in the case group than in the control group. Albumin was lower in the case group than in the control group. All differences were statistically significant. The infection rates of Klebsiella pneumoniae (P = 0.030), Pseudomonas aeruginosa (P = 0.043), and Candida albicans (P = 0.032) were significantly different between the two groups. CONCLUSION: Compared with those without diabetes, the infection rates of Klebsiella pneumoniae, Pseudomonas aeruginosa, and Candida albicans were higher in patients with combined CAP/T2D.

Asunto(s)

Infecciones Comunitarias Adquiridas , Diabetes Mellitus Tipo 2 , Diagnóstico Precoz , Humanos , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/microbiología , Diabetes Mellitus Tipo 2/epidemiología , Infecciones Comunitarias Adquiridas/diagnóstico , Infecciones Comunitarias Adquiridas/microbiología , Infecciones Comunitarias Adquiridas/sangre , Infecciones Comunitarias Adquiridas/epidemiología , Femenino , Masculino , Persona de Mediana Edad , Anciano , Neumonía/diagnóstico , Neumonía/sangre , Neumonía/microbiología , Estudios de Casos y Controles , Metagenómica/métodos , Adulto , Neumonía Bacteriana/diagnóstico , Neumonía Bacteriana/microbiología , Neumonía Bacteriana/sangre , Neumonía Bacteriana/epidemiología

RESUMEN

Single particle collision is an important tool for size analysis at the individual particle level; however, due to complex dynamic behaviors of nanoparticles on the surface of an electrode, the accuracy of size discrimination is limited. A silver (Ag) nanoparticle (NP) was chosen as the research target, and the dynamic behavior of Ag NPs was simplified by enhancing adsorption between Ag NP and Au ultramicroelectrode (UME) in alkaline media. Immediately after, accurate dynamic and thermodynamic information on single Ag NP was accurately extracted from collision events, including current intensity, transferred charge, and duration time. On the basis that there were differences between parameters of different-sized Ag NPs, multiparameter size discrimination was proposed, which improved the accuracy compared to single-parameter discrimination. More intriguingly, multiparameter analysis was combined with artificial intelligence, a tool adept at processing multidimensional data, for the first time. Finally, artificial intelligence-assisted multiparameter size discrimination was successfully used to intelligently distinguish mixed Ag NPs, with an optimal accuracy of more than 95%. To sum up, the artificial intelligence-assisted multiparameter method showed an excellent ability to quickly achieve the most accurate size discrimination of nanoparticles at the level of individual particle and provide an effective guidance for the application of nanoparticles.