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1.
Plast Reconstr Surg ; 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38967637

RESUMEN

BACKGROUND: This study aimed to investigate the timing of and indications for the Tajima reverse U incision for correcting secondary unilateral cleft nasal deformities. METHODS: Non-syndromic patients with secondary cleft lip and nasal deformity who received Tajima reverse-U incision rhinoplasty were grouped by age (4-13 years, n=56;13-18 years, n=22; >18 years, n=18) and severity of deformity (mild deformity, n=7; moderate deformity=22; severity deformity=67) during 5-year follow-up. Face-Q assessment, a rating scale, and nasal symmetry measurements were employed in this study. RESULTS: Ninety-six patients completed the FACE-Q assessment for the nose and nostril. The results showed higher satisfaction with nostril appearance 1-week after surgery (85.95±13.01) compared with pre-operation (79.72±11.89) and maintained 5-year follow-up (82.61±14.06). Significant differences were observed in five nasal parameters (nasal height ratio, one-fourth media part of nostril height ratio, nasal sill height ratio, columellar angle, and inner nostril height-to-width ratio (cleft)) for 1-week postoperatively and the corrected outcome of the Tajima technique was maintained 5 years after surgery in aged 4-13 years group. The same statistically significant changes were found in nasal sill height ratio in mild deformity group and nostril width ratio, one-fourth media part of nostril height ratio, columellar angle, and inner nostril height-to-width ratio (cleft) in moderate deformity group. CONCLUSION: The Tajima procedure was beneficial for preadolescent children and children with mild to moderate unilateral cleft nasal deformities.

2.
ChemMedChem ; : e202400311, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38973697

RESUMEN

Target-based high-throughput screening (HTS) is an efficient way to identify potent drugs. However, the accuracy of HTS could be affected by Pan-Assay Interference Compounds (PAINS). One reason for the generation of PAINS is that the inherent photophysical property of screened compounds could interfere with typically used assay signals including absorption and fluorescence. Our previous studies indicate that the fluorescent probe based on the fluorophore with characteristics of aggregation-induced emission (AIE) could provide high accuracy of HTS, especially for the fluorescent natural products. Herein, we report an AIE-based fluorescent probe for the main protease (Mpro) of SARS-CoV-2. We designed and synthesized an AIE fluorescent probe ZLHG5, which has a site that can be specifically cleaved by Mpro to produce a light-up fluorescence. Thanks to the large Stokes shift of AIE fluorophore (~300 nm), the probe could be effectively used for HTS of Mpro inhibitors. After screening a library of fluorescent natural products with ZLHG5, we obtained two coumarin-originated natural compounds with potent inhibitory activity towards Mpro protease. This study provides both useful fluorescent HTS probe and potent inhibitors for Mpro protease.

3.
Medicine (Baltimore) ; 103(27): e38812, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38968470

RESUMEN

Acquired undescended testes were once considered a sporadic disease. In recent years, reports suggest that they are not uncommon, with an incidence rate about 3 times that of congenital undescended testes. The etiology of acquired undescended testes remains inconclusive, clinical diagnostic standards are unclear, and treatment approaches are still controversial. There is ongoing debate about the mechanism of testicular ascent. The prevailing view is that acquired undescended testes occur due to the partial absorption of the gubernaculum, which forms part of the parietal peritoneum. The residual gubernacular fibers continuously pull on the spermatic cord, preventing the spermatic cord from elongating proportionately to somatic growth, leading to a re-ascent of the testis. Acquired undescended testes may increase the risk of testicular cancer, but this is still debated. The preferred treatment method is also controversial. However, surgical fixation has an immediate effect; no studies have proven that early surgery improves fertility in patients. The etiology of acquired undescended testes is closely related to the continuous pull of the residual gubernacular fibers on the spermatic cord, which prevents the cord from extending proportionately to body growth. There are no clear diagnostic standards for acquired undescended testes yet, and spontaneous descent is possible, so testicular fixation surgery may not be the preferred treatment method.


Asunto(s)
Criptorquidismo , Humanos , Masculino , Criptorquidismo/terapia , Criptorquidismo/diagnóstico , Criptorquidismo/etiología , Testículo , Orquidopexia
4.
J Gastrointest Oncol ; 15(3): 1198-1213, 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-38989424

RESUMEN

Background: Cholangiocarcinoma (CCA), a highly lethal tumor of the hepatobiliary system originating from bile duct epithelium, can be divided into the intrahepatic, hilar, and extrahepatic types. Due to its insidious onset and atypical early clinical symptoms, the overall prognosis is poor. One of the important factors contributing to the poor prognosis of CCA is the occurrence of perineural invasion (PNI), but the specific mechanisms regarding how it contributes to the occurrence of PNI are still unclear. The main purpose of this study is to explore the molecular mechanism leading to the occurrence of PNI and provide new ideas for clinical treatment. Methods: CCA cell lines and Schwann cells (SCs) were stimulated to observe the changes in cell behavior. SCs cocultured with tumor supernatant and SCs cultured in normal medium were subjected to transcriptome sequencing to screen the significantly upregulated genes. Following this, the two types of tumor cells were cultured with SC supernatant, and the changes in behavior of the tumor cells were observed. Nonobese diabetic-severe combined immunodeficiency disease (NOD-SCID) mice were injected with cell suspension supplemented with nerve growth factor (NGF) via the sciatic nerve. Four weeks later, the mice were euthanized and the tumor sections were removed and stained. Results: Nerve invasion by tumor cells was common in CCA tissues. SCs were observed in tumor tissues, and the number of SCs in tumor tissues and the degree of PNI were much higher than were those in normal tissues or tissues without PNI. The overall survival time was shorter in patients with CCA with PNI than in patients without PNI. SCs were enriched in CCA tissues, indicating the presence of PNI and associated with poor prognosis in CCA patients. CCA was found to promote NGF secretion from SCs in vitro. After the addition of exogenous NGF in CCA cell culture medium, the proliferation activity and migration ability of CCA cells were significantly increased, suggesting that SCs can promote the proliferation and migration of CCA through the secretion of NGF. NGF, in turn, was observed to promote epithelial-mesenchymal transition in CCA through tropomyosin receptor kinase A (TrkA), thus promoting its progression. Tumor growth in mice shows that NGF can promote PNI in CCA. Conclusions: In CCA, tumor cells can promote the secretion of NGF by SCs, which promotes the progression of CCA and PNI by binding to its high-affinity receptor TrkA, leading to poor prognosis.

5.
Theor Appl Genet ; 137(7): 172, 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38935162

RESUMEN

Phosphorus (P) is an essential element for plant growth, and its deficiency can cause decreased crop yield. This study systematically evaluated the low-phosphate (Pi) response traits in a large population at maturity and seedling stages, and explored candidate genes and their interrelationships with specific traits. The results revealed a greater sensitivity of seedling maize to low-Pi stress compared to that at maturity stage. The phenotypic response patterns to low-Pi stress at different stages were independent. Chlorophyll content was found to be a potential indicator for screening low-Pi-tolerant materials in the field. A total of 2900 and 1446 significantly associated genes at the maturity and seedling stages were identified, respectively. Among these genes, 972 were uniquely associated with maturity traits, while 330 were specifically detected at the seedling stage under low-Pi stress. Moreover, 768 and 733 genes were specifically associated with index values (low-Pi trait/normal-Pi trait) at maturity and seedling stage, respectively. Genetic network diagrams showed that the low-Pi response gene Zm00001d022226 was specifically associated with multiple primary P-related traits under low-Pi conditions. A total of 963 out of 2966 genes specifically associated with traits under low-Pi conditions or index values were found to be induced by low-Pi stress. Notably, ZmSPX4.1 and ZmSPX2 were sharply up-regulated in response to low-Pi stress across different lines or tissues. These findings advance our understanding of maize's response to low-Pi stress at different developmental stages, shedding light on the genes and pathways implicated in this response.


Asunto(s)
Fenotipo , Fósforo , Plantones , Estrés Fisiológico , Zea mays , Zea mays/genética , Zea mays/crecimiento & desarrollo , Plantones/genética , Plantones/crecimiento & desarrollo , Estrés Fisiológico/genética , Fósforo/metabolismo , Genes de Plantas , Estudio de Asociación del Genoma Completo , Clorofila/metabolismo , Sitios de Carácter Cuantitativo , Regulación de la Expresión Génica de las Plantas , Estudios de Asociación Genética , Polimorfismo de Nucleótido Simple
6.
Exp Cell Res ; 440(2): 114148, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38936760

RESUMEN

UBA5, a ubiquitin-like activated enzyme involved in ufmylation and sumoylation, presents a viable target for pancreatic and breast cancer treatments, yet its role in lung adenocarcinoma (LUAD) remains underexplored. This study reveals UBA5's tumor-promoting effect in LUAD, as evidenced by its upregulation in patients and positive correlation with TNM stages. Elevated UBA5 levels predict poor outcomes for these patients. Pharmacological inhibition of UBA5 using DKM 2-93 significantly curtails the growth of A549, H1299, and cisplatin-resistant A549 (A549/DDP) LUAD cells in vitro. Additionally, UBA5 knockdown via shRNA lentivirus suppresses tumor growth both in vitro and in vivo. High UBA5 expression adversely alters the tumor immune microenvironment, affecting immunostimulators, MHC molecules, chemokines, receptors, and immune cell infiltration. Notably, UBA5 expression correlates positively with M2 macrophage infiltration, the predominant immune cells in LUAD. Co-culture experiments further demonstrate that UBA5 knockdown directly inhibits M2 macrophage polarization and lactate production in LUAD. Moreover, in vivo studies show reduced M2 macrophage infiltration following UBA5 knockdown. UBA5 expression is also associated with increased tumor heterogeneity, including tumor mutational burden, microsatellite instability, neoantigen presence, and homologous recombination deficiency. Experiments indicate that UBA5 overexpression promotes cisplatin resistance in vitro, whereas UBA5 inhibition enhances cisplatin sensitivity in both in vitro and in vivo settings. Overall, these findings suggest that targeting UBA5 inhibits LUAD by impeding cancer cell proliferation, M2 macrophage polarization, and cisplatin resistance.


Asunto(s)
Adenocarcinoma del Pulmón , Cisplatino , Resistencia a Antineoplásicos , Neoplasias Pulmonares , Humanos , Cisplatino/farmacología , Resistencia a Antineoplásicos/efectos de los fármacos , Resistencia a Antineoplásicos/genética , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/tratamiento farmacológico , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/metabolismo , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/genética , Animales , Ratones , Proliferación Celular/efectos de los fármacos , Macrófagos/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Enzimas Activadoras de Ubiquitina/metabolismo , Enzimas Activadoras de Ubiquitina/genética , Enzimas Activadoras de Ubiquitina/antagonistas & inhibidores , Femenino , Microambiente Tumoral/efectos de los fármacos , Ratones Desnudos , Línea Celular Tumoral , Antineoplásicos/farmacología , Masculino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos
7.
Theor Appl Genet ; 137(7): 158, 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38864891

RESUMEN

Examining the connection between P and starch-related signals can help elucidate the balance between nutrients and yield. This study utilized 307 diverse maize inbred lines to conduct multi-year and multi-plot trials, aiming to explore the relationship among P content, starch content, and 100-kernel weight (HKW) of mature grains. A significant negative correlation was found between P content and both starch content and HKW, while starch content showed a positive correlation with HKW. The starch granules in grains with high-P and low-starch content (HPLS) were significantly smaller compared to grains with low-P high-starch content (LPHS). Additionally, mian04185-4 (HPLS) exhibited irregular and loosely packed starch granules. A significant decrease in ZmPHOs genes expression was detected in the HPLS line ZNC442 as compared to the LPHS line SCML0849, while no expression difference was observed in AGPase encoding genes between these two lines. The down-regulated genes in ZNC442 grains were enriched in nucleotide sugar and fatty acid anabolic pathways, while up-regulated genes were enriched in the ABC transporters pathway. An accelerated breakdown of fat as the P content increased was also observed. This implied that HPLS was resulted from elevated lipid decomposition and inadequate carbon sources. The GWAS analysis identified 514 significantly associated genes, out of which 248 were differentially expressed. Zm00001d052392 was found to be significantly associated with P content/HKW, exhibiting high expression in SCML0849 but almost no expression in ZNC442. Overall, these findings suggested new approaches for achieving a P-yield balance through the manipulation of lipid metabolic pathways in grains.


Asunto(s)
Fósforo , Almidón , Transcriptoma , Zea mays , Zea mays/genética , Zea mays/metabolismo , Almidón/metabolismo , Fósforo/metabolismo , Grano Comestible/genética , Grano Comestible/metabolismo , Regulación de la Expresión Génica de las Plantas , Estudio de Asociación del Genoma Completo , Sitios de Carácter Cuantitativo , Fenotipo
8.
Am J Cancer Res ; 14(5): 2037-2054, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38859843

RESUMEN

Glioblastoma is the most common cancer in the brain, resistant to conventional therapy and prone to recurrence. Therefore, it is crucial to explore novel therapeutics strategies for the treatment and prognosis of GBM. In this study, through analyzing online datasets, we elucidated the expression and prognostic value of POLR2J and its co-expressed genes in GBM patients. Functional experiments, including assays for cell apoptosis and cell migration, were used to explore the effects of POLR2J and vorinostat on the proliferation and migration of GBM cells. The highest overexpression of POLR2J, among all cancer types, was observed in GBM. Furthermore, high expression of POLR2J or its co-expressed genes predicted a poor outcome in GBM patients. DNA replication pathways were significantly enriched in the GBM clinical samples with high POLR2J expression, and POLR2J suppression inhibited proliferation and triggered cell cycle G1/S phase arrest in GBM cells. Moreover, POLR2J silencing activated the unfolded protein response (UPR) and significantly enhanced the anti-GBM activity of vorinostat by suppressing cell proliferation and inducing apoptosis. Additionally, POLR2J could interact with STAT3 to promote the metastatic potential of GBM cells. Our study identifies POLR2J as a novel oncogene in GBM progression and provides a promising strategy for the chemotherapeutic treatment of GBM.

9.
ISA Trans ; 2024 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-38851926

RESUMEN

When legged robots perform complex tasks in unstructured environments, falls are inevitable due to unknown external disturbances. However, current research mainly focuses on the locomotion control of legged robots without falling. This paper proposes a comprehensive decision-making and control framework to address the falling over of quadruped robots. First, a capturability-based fall prediction algorithm is derived for planar single-contact and 3D multi-contact locomotion with a predefined gait sequence. For safe fall control, a novel contact-implicit trajectory optimization method is proposed to generate both state and input trajectories and contact mode sequences. Specifically, incorporating uncertainty into the system and terrain models enables mitigating the non-smoothness of contact dynamics while improving the robustness of the resulting trajectories. Furthermore, a model-free deep reinforcement learning-based approach is presented to achieve fall recovery after the robot completes a fall. Experimental results demonstrate that the proposed fall prediction algorithm accurately predicts robot falls with up to 95% accuracy approximately 395ms in advance. Compared to classical locomotion controllers, which often struggle to maintain balance under significant pushes or terrain perturbations, the presented framework can autonomously switch to the fall controller approximately 0.06s after the perturbation, effectively preventing falls or achieving recovery with a threefold reduction in touchdown impact velocity. These findings highlight the effectiveness of the proposed framework in enhancing the stability and safety of legged robots in unstructured environments.

10.
Artículo en Inglés | MEDLINE | ID: mdl-38829448

RESUMEN

The relationship between infectious agents and autoimmune diseases is a complex issue. In recent years, increasing clinical cases have indicated that infectious agents play an important role in the development of autoimmune diseases. Molecular mimicry is currently widely regarded as the primary pathogenic mechanism of various autoimmune diseases in humans. Components of infectious agents can undergo molecular mimicry with components in patients' bodies, leading to the development of various autoimmune diseases. In this article, we provide a brief overview of current research of the current research status on the relationship between infectious agents and autoimmune diseases, and describe our current understanding of their mechanisms of action in order to better understand the pathogenesis, diagnosis, and treatment of autoimmune diseases.

11.
Bioresour Technol ; 406: 131057, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38945502

RESUMEN

The quinoid component of humic acids (HAs) had been studied as exogenous electron mediators (EMs), but the redox-mediating abilities of other functional groups remained unclear. This study evaluated the effects of various HAs functional groups on cellular respiration and extracellular electron transfer. The three EMs increased the current density compared to the control. Current density increased significantly after adding ultraviolet-irradiated HAs (UV-HAs), suggesting that nitrogenous group-mediated redox reactions contributed to high-density current generation. Structural equation model (SEM) results indicated that the contribution of nitrogen-containing groups to electron transfer could exceed 20%. This study proposed a synergistic mechanism: in the soil microbial fuel cells (soil-MFCs), HAs accelerated their component evolution through irreversible redox reactions and promoted extracellular electron transfer. Additionally, HAs-induced high expression of c-Cyts could further enhance high-density current generation. This study demonstrates that humic acids enhance electron transfer and current in bioelectrochemical systems, aiding sustainable energy optimization.

12.
Bioresour Technol ; 406: 131008, 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38897547

RESUMEN

This study investigated the nutrient removal and microbial community succession in moving bed biofilm reactor under stable and three levels of influent carbon/nitrogen (C/N) ratio fluctuation (± 10%, ± 20%, and ± 30%). Under the conditions of influent C/N ratio fluctuation, the removal efficiency of COD and PO43--P decreased 4.7-6.4% and 3.7-12.9%, respectively, while the nitrogen removal was almost unaffected. A sharp decrease in the content of culturable functional bacteria related to nitrogen and phosphorus removal including nitrite-oxidizing bacteria (NOB), aerobic denitrifying bacteria (DNB), and polyphosphate-accumulating organisms (PAOs) from the carrier biofilm was observed. Sequencing analysis revealed that the abundance of Candidatus Competibacter increased 10.3-25.9% and became the dominant genus responsible for denitrification, potentially indicating that nitrate was removed via endogenous denitrification under the influent C/N ratio fluctuation. The above results will provide basic data for the nutrient removal in decentralized wastewater treatment under highly variable influent conditions.

13.
Bioresour Technol ; 406: 131007, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38901747

RESUMEN

This study investigated the effects of carbon/nitrogen (C/N) ratio on microbial community in moving bed biofilm reactor (MBBR) using metagenomic analysis, and the dynamic changes of relevant antibiotic resistance genes (ARGs) were also analyzed. The results showed that under low C/N ratio, MBBR exhibited average removal rates of 98.41 % for ammonia nitrogen and 75.79 % for total nitrogen. Metagenomic analysis showed low C/N ratio altered the structure of biofilm and water microbiota, resulting in the detachment of bacteria such as Actinobacteria from biofilm into water. Furthermore, sulfamethazine (SMZ)-resistant bacteria and related ARGs were released into water under low C/N ratio, which lead to the increase of SMZ resistance rate to 90%. Moreover, most dominant genera are potential hosts for both nitrogen cycle related genes and ARGs. Specifically, Nitrosomonas that carried gene sul2 might be released from biofilm into water. These findings implied the risks of antibiotic resistance dissemination in MBBR under low C/N ratio.

14.
J Hazard Mater ; 475: 134908, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-38889459

RESUMEN

Previous research has established a MES embedding a microbial electrode to facilitate the degradation of antibiotics in water. We modified microbial electrodes in the MES with PEDOT and rGO to enhance electron utilization on electrodes and to further promote antibiotic degradation. Density functional theory calculations on the SMX molecule indicated that the C4-S8 and S8-N27 bonds are the most susceptible to electron attack. The introduction of various functional groups and multivalent elements enhanced the electrodes' capacitance and electron mediation capabilities. This led to enhance both electron utilization on the electrodes and the removal efficiency of SMX. After 120 h, the degradation efficiency of SMX by PEDOT and rGO-modified electrodes increased by 45.47 % and 25.19 %, respectively, compared to unmodified electrodes. The relative abundance of sulfate-reducing and denitrifying bacteria significantly increased in PEDOT and rGO-modified electrodes, while the abundance of nitrifying bacteria and potential antibiotic resistance gene host microbes significantly decreased. The impact of PEDOT modification positively influenced microbial Cellular Processes, including cell growth, death, and motility. This study provides insights into the mechanisms of direct electron involvement in antibiotic degradation steps in microbial electrochemistry, and provides a possible path for improved strategies in antibiotic degradation and sustainable environmental remediation.


Asunto(s)
Antibacterianos , Electrodos , Electrones , Polímeros , Antibacterianos/química , Polímeros/química , Bacterias/metabolismo , Bacterias/genética , Grafito/química , Compuestos Bicíclicos Heterocíclicos con Puentes/química , Técnicas Electroquímicas , Contaminantes Químicos del Agua/química
15.
Aging (Albany NY) ; 16(12): 10546-10562, 2024 06 24.
Artículo en Inglés | MEDLINE | ID: mdl-38916406

RESUMEN

Metastasis is the primary cause of cancer-related deaths, and colorectal cancer (CRC) liver metastasis is a major poor prognostic factor in CRC. NAT1 (N-acetyltransferase 1) plays a crucial role in the invasive and metastatic processes of colorectal cancer. The role and molecular mechanism of NAT1 on tumor cells were verified by establishing a cell model of overexpression and knockdown of NAT1, and further verified by establishing a liver metastasis model of colorectal cancer for animal experiments. In vivo and in vitro experiments have demonstrated that overexpression of NAT1 reduces the ability of metastasis and invasion of colorectal cancer cells. NAT1 overexpression inhibits the PI3K/AKT/mTOR signaling pathway, thereby suppressing the EMT (epithelial-mesenchymal transition) process and glycolytic ability of tumor cells. Additionally, decreased glycolytic ability results in reduced VEGF (Vascular endothelial growth factor) expression in colorectal cancer cells. The decreased VEGF expression leads to decreased angiogenesis and vascular permeability in liver metastases, ultimately reducing the occurrence of liver metastasis. Our findings highlight that overexpression of NAT1 significantly inhibits the PI3K/AKT/mTOR signaling pathway, thereby suppressing EMT, glycolytic ability, and VEGF expression in colorectal cancer cells, collectively preventing the development of liver metastasis.


Asunto(s)
Arilamina N-Acetiltransferasa , Neoplasias Colorrectales , Transición Epitelial-Mesenquimal , Glucólisis , Neoplasias Hepáticas , Transducción de Señal , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Transición Epitelial-Mesenquimal/genética , Humanos , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Animales , Arilamina N-Acetiltransferasa/genética , Arilamina N-Acetiltransferasa/metabolismo , Línea Celular Tumoral , Ratones , Serina-Treonina Quinasas TOR/metabolismo , Isoenzimas/metabolismo , Isoenzimas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Regulación Neoplásica de la Expresión Génica , Ratones Desnudos
16.
Cancer Sci ; 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38890815

RESUMEN

Common epidermal growth factor receptor (EGFR) mutations are usually not considered for immunotherapy in non-small cell lung cancer (NSCLC) due to poor efficacy. However, whether uncommon EGFR mutations are suitable for immunotherapy has not been thoroughly studied. Thus, we explored the tumor immune microenvironment (TME) features in uncommon EGFR mutant NSCLC. In this study, a total of 41 patients with EGFR mutations were included, the majority (85.4%) of whom were stage I. Among them, 22 patients harbored common mutations, while 19 patients presented with uncommon mutations. Compared with common mutations, uncommon mutations exhibited more infiltrating T cells and fewer M2 macrophages, upregulated expression of antigen processing and a presentation pathway. Unsupervised clustering based on the mIF profile identified two classes with heterogeneous TME in uncommon mutations. Class 1 featured the absence of PD-1+ cytotoxic T cell infiltration, and class 2 displayed a hotter TME because of the downregulated expression of hypoxia (p < 0.001), oxidative phosphorylation (p = 0.009), and transforming growth factor beta signaling (p = 0.01) pathways as well as increased expression of CTLA4 (p = 0.001) and PDCD1 (p = 0.004). The association of CTLA4 and PDCD1 with TME profiles was validated in a TCGA lung adenocarcinoma cohort with uncommon EGFR mutations. Our study reveals the distinct and heterogeneous TME features in uncommon EGFR mutant NSCLC.

17.
Food Res Int ; 189: 114533, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38876603

RESUMEN

Glutinous rice is extensively consumed due to its nutritious content and wonderful flavor. However, glutinous rice flour has a high glycemic index, and the storage deterioration of sweet dumplingsissevere. Transglutaminase (TG) was used to cross-link glutinous rice protein and improve the characteristics of glutinous rice products. The findings demonstrated that TG significantly catalysed protein cross-linking to form a dense protein network, reduced the viscosity of glutinous rice paste and improved the thermal stability. The protein network may physically block the access of starch granules to digestive enzymes to lower the digestion rate of starch, and attenuate the damage of ice crystal molecules to the starch structure to improve the freezing stability of starch gels. The cracking rate and water loss of sweet dumplings prepared using glutinous rice flour with TG treated for 60 min reduced significantly. In conclusion, this study broadened the application of TG in starch products.


Asunto(s)
Digestión , Harina , Manipulación de Alimentos , Oryza , Almidón , Transglutaminasas , Oryza/química , Transglutaminasas/metabolismo , Almidón/metabolismo , Almidón/química , Harina/análisis , Manipulación de Alimentos/métodos , Viscosidad , Proteínas de Plantas/metabolismo , Proteínas de Plantas/química
18.
Nat Commun ; 15(1): 5197, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38890294

RESUMEN

Untethered miniature soft robots have significant application potentials in biomedical and industrial fields due to their space accessibility and safe human interaction. However, the lack of selective and forceful actuation is still challenging in revolutionizing and unleashing their versatility. Here, we propose a focused ultrasound-controlled phase transition strategy for achieving millimeter-level spatially selective actuation and Newton-level force of soft robots, which harnesses ultrasound-induced heating to trigger the phase transition inside the robot, enabling powerful actuation through inflation. The millimeter-level spatial resolution empowers single robot to perform multiple tasks according to specific requirements. As a concept-of-demonstration, we designed soft robot for liquid cargo delivery and biopsy robot for tissue acquisition and patching. Additionally, an autonomous control system is integrated with ultrasound imaging to enable automatic acoustic field alignment and control. The proposed method advances the spatiotemporal response capability of untethered miniature soft robots, holding promise for broadening their versatility and adaptability.


Asunto(s)
Robótica , Robótica/instrumentación , Robótica/métodos , Diseño de Equipo , Humanos , Ondas Ultrasónicas , Transición de Fase , Ultrasonografía/métodos , Ultrasonografía/instrumentación
19.
ACS Synth Biol ; 13(6): 1893-1905, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38825826

RESUMEN

Gas-fermenting Clostridium species hold tremendous promise for one-carbon biomanufacturing. To unlock their full potential, it is crucial to unravel and optimize the intricate regulatory networks that govern these organisms; however, this aspect is currently underexplored. In this study, we employed pooled CRISPR interference (CRISPRi) screening to uncover a wide range of functional transcription factors (TFs) in Clostridium ljungdahlii, a representative species of gas-fermenting Clostridium, with a special focus on TFs associated with the utilization of carbon resources. Among the 425 TF candidates, we identified 75 and 68 TF genes affecting the heterotrophic and autotrophic growth of C. ljungdahlii, respectively. We focused our attention on two of the screened TFs, NrdR and DeoR, and revealed their pivotal roles in the regulation of deoxyribonucleoside triphosphates (dNTPs) supply, carbon fixation, and product synthesis in C. ljungdahlii, thereby influencing the strain performance in gas fermentation. Based on this, we proceeded to optimize the expression of deoR in C. ljungdahlii by adjusting its promoter strength, leading to an improved growth rate and ethanol synthesis of C. ljungdahlii when utilizing syngas. This study highlights the effectiveness of pooled CRISPRi screening in gas-fermenting Clostridium species, expanding the horizons for functional genomic research in these industrially important bacteria.


Asunto(s)
Sistemas CRISPR-Cas , Clostridium , Fermentación , Factores de Transcripción , Clostridium/genética , Clostridium/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Sistemas CRISPR-Cas/genética , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Regiones Promotoras Genéticas/genética , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas/genética , Ingeniería Metabólica/métodos , Gases/metabolismo
20.
J Org Chem ; 89(12): 8878-8887, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38845522

RESUMEN

A one-pot approach has been developed for the synthesis of α-ketothioamide derivatives from sulfur ylides, nitrosobenzenes, and thioacetic acid. This protocol is carried out under mild reaction conditions in generally moderate to excellent yields without any precious catalysts, affording the derivatives with structural diversity. Additionally, a possible mechanism for this chemical transformation is proposed.

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