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MicroRNA (miRNA) detection is a critical aspect of disease diagnosis, and recent studies indicate that miRNA-622 could be a potential target for lung cancer. Herein, Cu single atoms were anchored on graphitic carbon nitride (Cu SAs@CN) as a coreaction accelerator applied in luminol-H2O2 system, thereby establishing an efficient and sensitive electrochemiluminescence (ECL) biosensor for miRNA-622 detection. Cu SAs@CN was explored to possess excellent enzyme-like activities that promote the generation of abundant reactive oxygen species, which amplified ECL emission. Meanwhile, in order to improve the accuracy and sensitivity for miRNA-622 detection, the highly specific trans-cleavage ability of CRISPR/Cas12a was combined with a catalytic hairpin assembly strategy. Therefore, an ECL biosensor for miRNA-622 detection was systematically constructed as a proof of concept, achieving an ultralow limit of detection of 1.09 fM, and the feasibility was demonstrated in human serum samples. The findings of this research provide a promising strategy to enhance the ECL response using versatile single-atom catalysts, thus advancing the development of ECL biosensing applications.
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Técnicas Biosensibles , Cobre , Técnicas Electroquímicas , Grafito , Mediciones Luminiscentes , Luminol , MicroARNs , Técnicas Biosensibles/métodos , Humanos , MicroARNs/análisis , MicroARNs/sangre , Cobre/química , Grafito/química , Luminol/química , Límite de Detección , Peróxido de Hidrógeno/química , Compuestos de Nitrógeno/química , Catálisis , Proteínas Asociadas a CRISPR , Sistemas CRISPR-Cas , Proteínas Bacterianas , EndodesoxirribonucleasasRESUMEN
The frequency and distribution of meiotic crossovers are tightly controlled; however, variation in this process can be observed both within and between species. Using crosses of two natural Arabidopsis thaliana accessions, Col and Ler, we mapped a crossover modifier locus to semidominant polymorphisms in SUPPRESSOR OF NPR1-1 INDUCIBLE 1 (SNI1), which encodes a component of the SMC5/6 complex. The sni1 mutant exhibits a modified pattern of recombination across the genome with crossovers elevated in chromosome distal regions but reduced in pericentromeres. Mutations in SNI1 result in reduced crossover interference and can partially restore the fertility of a Class I crossover pathway mutant, which suggests that the protein affects noninterfering crossover repair. Therefore, we tested genetic interactions between SNI1 and both RECQ4 and FANCM DNA helicases, which showed that additional Class II crossovers observed in the sni1 mutant are FANCM independent. Furthermore, genetic analysis of other SMC5/6 mutants confirms the observations of crossover redistribution made for SNI1 The study reveals the importance of the SMC5/6 complex in ensuring the proper progress of meiotic recombination in plants.
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Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Intercambio Genético/fisiología , ADN Helicasas/metabolismo , Variación Genética , Meiosis/fisiología , Proteínas Nucleares/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/genética , ADN Helicasas/genética , Regulación de la Expresión Génica de las Plantas , Proteínas Nucleares/genética , Dominios ProteicosRESUMEN
BACKGROUND: Both video-assisted thoracoscopic surgery (VATS) thymectomy and robot-assisted thoracoscopic surgery (RATS) thymectomy have been suggested as technically sound approaches for early-stage thymic epithelial tumors. However, the choice of VATS or RATS thymectomy for large and advanced thymic epithelial tumors remains controversial. In this study, the perioperative outcomes of VATS and RATS thymectomy were compared in patients with large thymic epithelial tumors (size ≥5.0 cm). METHODS: A total of 113 patients with large thymic epithelial tumors who underwent minimally invasive surgery were included. Sixty-three patients underwent RATS, and 50 patients underwent VATS. Patient characteristics and perioperative variables were compared. RESULTS: Compared with the VATS group, the RATS group experienced a shorter operation time (median: 110 min vs.130 min; P < 0.001) and less blood loss (30.00 ml vs. 100.00 ml, P < 0.001). No patients in the RATS group needed conversion to open surgery, but in the VATS series, five patients required conversion to open procedures (0% vs. 14.29%, P = 0.054). The rate of concomitant resection in the RATS group was similar to that in the VATS group (11.43% vs. 5.71%; P = 0.673). There was no significant difference between the two groups in the duration of chest tube (P = 0.587), postoperative complications (P = 1.000), and the duration of postoperative hospital stay (P = 0.141). CONCLUSION: For large thymic epithelial tumors, RATS thymectomy can be performed safely and effectively in a radical fashion. Due to the advanced optics and precise instrument control, concomitant resections can be easily achieved in larger thymic epithelial tumors using the robotic approach.
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Neoplasias Glandulares y Epiteliales , Robótica , Neoplasias del Timo , Humanos , Timectomía/métodos , Cirugía Torácica Asistida por Video/métodos , Estudios Retrospectivos , Neoplasias del Timo/cirugía , Neoplasias del Timo/patología , Neoplasias Glandulares y Epiteliales/cirugíaRESUMEN
Psoriasis is an inflammatory immune-mediated skin disease that significantly impacts physical and psychological well-being. Adalimumab (ADA), a tumor necrosis factor (TNF)-α antagonist, is used to treat psoriasis. This study was performed to assess the efficacy and safety of ADA, identify the fecal microbial composition of psoriasis patients, and explore the effect of ADA on the gut bacteria in psoriasis. Clinical characteristics of the 13 psoriasis patients before (BT) and after ADA treatment (AT) were collected. And total 39 fecal samples from 13 psoriasis patients (BT and AT) and 13 healthy controls were sequenced by 16S rRNA and analyzed by informatics methods. After three months' ADA treatment, physician global assessment (PGA), psoriasis area and severity index (PASI), dermatology life quality index (DLQI), state-trait anxiety inventory (STAI), and itch numeric rating scale (NRS) scores all decreased, and there were no severe adverse effects. Besides, the microbiota of the psoriasis group differed from that of the healthy group, but no microbial diversity and composition alteration were observed between psoriasis patients BT and AT. We suggested that the gut microbiome may change more slowly than skin lesions. Long-term follow-up of patients treated with ADA and further study of psoriasis based on microbiota may provide more evidence for the treatment of psoriasis.
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Microbioma Gastrointestinal , Psoriasis , Adalimumab/uso terapéutico , Humanos , Psoriasis/tratamiento farmacológico , ARN Ribosómico 16S , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Factor de Necrosis Tumoral alfaRESUMEN
In passively mode-locked fiber lasers (PMLFLs), the dissipative solitons (DSs) can self-organize to form complex structures through delicate interactions. However, it is still elusive to control these soliton structures by external influences. We here find that at a certain critical power, the location between two soliton molecules can be controlled by a slow modulated pump power. After applying the pump power with periodic fluctuation, two soliton molecules oscillate from the state of soliton molecular complex to stable distribution with maximum inter-molecular separation. During this process, the internal structure of each soliton molecule keeps steady. The slow gain depletion and recovery mechanism which plays a dominant role affects the motion of soliton molecules. These results could further expand the molecular analogy of spectroscopy and stimulate the development of optical information storage and processing.
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BACKGROUND: Bamboo is a very important forest resource. However, the prolonged vegetative stages and uncertainty of flowering brings difficulties in bamboo flowers sampling. Until now, the flowering mechanism of bamboo is still unclear. RESULTS: In this study, three successive stages of flowering buds and the corresponding vegetative buds (non-flowering stage) from Lei bamboo (Phyllostachys violascens) were collected for transcriptome analysis using Illumina RNA-Seq method. We generated about 442 million clean reads from the above samples, and 132,678 unigenes were acquired with N50 of 1080 bp. A total of 7266 differentially expressed genes (DEGs) were determined. According to expression profile and gene function analysis, some environmental stress responsive and plant hormone-related DEGs were highly expressed in the inflorescence meristem formation stage (TF_1) while some floral organ development related genes were up-regulated significantly in floral organs determination stage (TF_2) and floral organs maturation (TF_3) stage, implying the essential roles of these DEGs in flower induction and maturation of Lei bamboo. Additionally, a total of 25 MADS-box unigenes were identified. Based on the expression profile, B, C/D and E clade genes were more related to floral organs development compared with A clade genes in Lei bamboo. CONCLUSIONS: This transcriptome data presents fundamental information about the genes and pathways involved in flower induction and development of Lei bamboo. Moreover, a critical sampling method is provided which could be benefit for bamboo flowering mechanism study.
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Perfilación de la Expresión Génica/métodos , Poaceae/genética , Flores/genética , Flores/crecimiento & desarrollo , Regulación de la Expresión Génica de las Plantas , Proteínas de Dominio MADS/clasificación , Proteínas de Dominio MADS/genética , Filogenia , Poaceae/crecimiento & desarrollo , ARN de Planta/química , ARN de Planta/genética , ARN de Planta/metabolismo , RNA-SeqRESUMEN
Homogalacturonan (HG) is the main component of pectins. HG methylesterification has recently emerged as a key determinant controlling cell attachment, organ formation, and phyllotaxy. However, whether and how HG methylesterification affects intercellular metabolite transport has rarely been reported. Here, we identified and characterized knockout mutants of the rice (Oryza sativa) OsQUA2 gene encoding a putative pectin methyltransferase. Osqua2 mutants exhibit a remarkable decrease in the degree of methylesterification of HG in the culm-sieve element cell wall and a markedly reduced grain yield. The culm of Osqua2 mutant plants contains excessive sucrose (Suc), and a 13CO2 feeding experiment showed that the Suc overaccumulation in the culm was caused by blocked Suc translocation. These and other findings demonstrate that OsQUA2 is essential for maintaining a high degree of methylesterification of HG in the rice culm-sieve element cell wall, which may be critical for efficient Suc partitioning and grain filling. In addition, our results suggest that the apoplastic pathway is involved in long-distance Suc transport in rice. The identification and characterization of the OsQUA2 gene and its functionality revealed a previously unknown contribution of HG methylesterification and provided insight into how modification of the cell wall regulates intercellular transport in plants.
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Metiltransferasas/metabolismo , Oryza/enzimología , Pectinas/metabolismo , Proteínas de Plantas/metabolismo , Sacarosa/metabolismo , Dióxido de Carbono/metabolismo , Comunicación Celular , Pared Celular/metabolismo , Esterificación , Genes Reporteros , Aparato de Golgi/metabolismo , Metiltransferasas/química , Metiltransferasas/genética , Mutación/genética , Fenotipo , Proteínas de Plantas/química , Proteínas de Plantas/genética , Haz Vascular de Plantas/metabolismo , Plantas Modificadas Genéticamente , Semillas/crecimiento & desarrollo , Fracciones Subcelulares/metabolismoRESUMEN
OBJECTIVE: To observe the outcome of stage I lung cancer treated by single-direction video-assisted thoracoscopic surgery (SD-VATS) major lung resection. METHODS: Between May 2006 and December 2013, a total of 3 743 patients with lung cancer underwent surgical treatment in Department of Thoracic Surgery, West China Hospital. The clinical date of 783 patients with stage I lung cancer treated by SD-VATS lobectomy/segmentectomy was analyzed retrospectively. There were 388 males and 395 females with a mean age of (59 ± 10) years (range 25 to 86 years). There were 740 cases of lobectomy and 43 cases of segmentectomy. Twenty patients underwent conversion to open thoracotomy. The methods of Kaplan-Meier survival analysis and Cox proportional hazard regression model were used to investigate the long term outcome and prognostic factors. RESULTS: The mean operating time was (145 ± 54) minutes (range 70 to 460 minutes). The median intraoperative blood loss was 50 (70) ml (range 5 to 1 200 ml). The postoperative morbidity and 90-day mortality were 13.3% and 1.0%, respectively. 5.9% patients were lost to follow-up. Finally 730 patients were enrolled into prognostic analysis with a mean follow-up time of (37 ± 18) months (range 5 to 92 months). The 5-year overall survival (OS), disease free survival (DFS), and cancer specific survival (CSS) were 83.8%, 74.4%, and 86.6%, respectively. The 5-year OS of IA and IB were 90.7% and 79.8% respectively. Univariate and multivariate analysis indicated that age ≥ 60 years (OR = 1.786, 95% CI: 1.081 to 2.948, P = 0.023), non-adenocarcinoma (OR = 1.647, 95% CI: 1.204 to 2.253, P = 0.002), and higher T status (OR = 2.709, 95% CI: 1.031 to 7.121, P = 0.043) were independently associated with poor OS; higher T status (OR = 5.118, 95% CI: 2.330 to 11.240, P = 0.000) and higher pathological stage status (OR = 0.369, 95% CI: 0.137 to 0.991, P = 0.048) were independently associated with poor DFS; non-adenocarcinoma (OR = 1.717, 95% CI: 1.224 to 2.409, P = 0.002) and higher T status (OR = 5.029, 95% CI: 1.432 to 17.659, P = 0.012) were independently associated with poor CSS. CONCLUSION: SD-VATS lung cancer resection is a safe and feasible method for the treatment of stage I lung cancer resulting good outcomes.
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Carcinoma de Pulmón de Células no Pequeñas/cirugía , Neoplasias Pulmonares/cirugía , Neumonectomía/métodos , Cirugía Torácica Asistida por Video , Adulto , Anciano , Anciano de 80 o más Años , Pérdida de Sangre Quirúrgica , China , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Tempo Operativo , Periodo Posoperatorio , Estudios Retrospectivos , ToracotomíaRESUMEN
DNA hydrogel represents a noteworthy biomaterial. The preparation of biosensors by combining DNA hydrogel with electrochemiluminescence can simplify the modification process and raise the experimental efficiency. In this study, an electrochemiluminescence (ECL) biosensor based on DNA hydrogel was fabricated to detect adenosine triphosphate (ATP) simply and quickly. CdTe-Ru@SiO2 nanospheres capable of ECL resonance energy transfer (RET) were synthesized and encapsulated CdTe-Ru@SiO2 in the DNA hydrogel to provide strong and stable ECL signals. DNA hydrogel avoided the labeling of ECL signal molecules. The aptamer of ATP as the linker of the hydrogel for the specificity of ATP detection. The cross-linked structure of the aptamer and the polymer chains was opened by ATP, and then the decomposition of the DNA hydrogel initiated the escape of CdTe-Ru@SiO2 to generate an ECL signal. The designed biosensor detected ATP without too much modification and complex experimental steps on the electrode surface, with good specificity and stability, and a wide linear range. The detection range was 10-5000 nM, and the detection limit was 6.68 nM (S/N = 3). The combination of DNA hydrogel and ECL biosensor provided a new way for clinical detection of ATP and other biomolecule.
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Adenosina Trifosfato , Aptámeros de Nucleótidos , Técnicas Biosensibles , ADN , Técnicas Electroquímicas , Hidrogeles , Límite de Detección , Mediciones Luminiscentes , Dióxido de Silicio , Técnicas Biosensibles/métodos , Adenosina Trifosfato/análisis , Aptámeros de Nucleótidos/química , Hidrogeles/química , Mediciones Luminiscentes/métodos , Técnicas Electroquímicas/métodos , ADN/química , Dióxido de Silicio/química , Telurio/química , Compuestos de Cadmio/química , HumanosRESUMEN
Atopic dermatitis (AD) is a common chronic inflammatory skin disease characterized by T helper 2 inflammation as the core pathogenic mechanism. MRGPRX2 plays a key role in nonhistamine allergies and neuroimmune mechanisms in chronic inflammatory dermatitis. However, the role of MRGPRX2 in AD and the development of type 2 inflammation is not yet clear. This study aimed to define the role of MRGPRX2 in type 2 inflammation development and cytokine release in AD by determining its levels in patients with AD and healthy controls. Furthermore, MrgprB2-conditional knockout (MrgprB2-/-) and wild-type mice were used to construct an MC903-induced AD mouse model to observe skin inflammation and cytokine release. Tryptase and its antagonist were applied separately to MrgprB2-/- mice with AD and wild-type mice with AD to confirm the role of the MRGPRB2-tryptase axis in the development of type 2 inflammation in AD. We found that AD severity and type 2 cytokine levels were not associated with IgE levels but were associated with MRGPRX2/MRGPRB2 expression. MrgprB2-/- mice with AD showed milder phenotypes and inflammatory infiltration in the skin than wild-type mice with AD. Tryptase released by MRGPRX2/MRGPRB2 activation is involved in the release of type 2 cytokines, which contributes to inflammatory development in AD.
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Dermatitis Atópica , Animales , Humanos , Ratones , Citocinas/metabolismo , Dermatitis Atópica/patología , Inflamación/patología , Mastocitos , Proteínas del Tejido Nervioso/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Receptores de Neuropéptido/metabolismo , Triptasas/metabolismoRESUMEN
Viaminate, a retinoic acid derivative developed in China, has been clinically used for acne treatment to regulate and control keratinocyte cell differentiation and proliferation, inhibit keratinization, reduce sebum secretion, and regulate immune and anti-inflammatory functions; however, its potential molecular mechanism has not yet been elucidated. Therefore, we induced ear acne in rats using Propionibacterium acnes and sebum application. Symptoms of ear redness, epidermal thickening, inflammatory reaction, keratin overproduction, subcutaneous oil, and triglyceride (TG) accumulation improved significantly in acne model rats treated with viaminate for 30 days. Transcriptome analysis of rat skin tissues suggested that viaminate had significant regulatory effects on fatty acid metabolism and cellular keratinization pathways. Molecular target prediction suggested that toll-like receptor 2 (TLR2) may be a key target of viaminate's therapeutic mechanism. Western blotting results confirmed that viaminate inhibited the TLR2 and its downstream pathways, nuclear factor-kappa B (NF-κB) [NF-κB inhibitor alpha (IκBα)/NF-κB-p65] and mitogen-activated protein kinases (MAPKs) [MAPK p38/c-Jun N-terminal kinase (JNK)/extracellular regulated kinase 1/2 (ERK1/2)] in acne vulgaris rats. In vitro studies revealed that viaminate treatment attenuated P. acnes proliferation and P. acnes-induced inflammatory response in human keratinocytes and has an inhibitory effect on the activation of NF-κB and MAPKs, while overexpression of TLR2 attenuated these effects. In conclusion, viaminate ameliorates P. acnes-induced acne by inhibiting the proliferation and inflammatory response of keratinocytes, ascribed to the deactivation of the TLR2-mediated NF-κB and MAPK pathways.
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Acné Vulgar , FN-kappa B , Ratas , Humanos , Animales , FN-kappa B/metabolismo , Propionibacterium acnes/metabolismo , Receptor Toll-Like 2 , Tretinoina , Acné Vulgar/tratamiento farmacológico , Acné Vulgar/metabolismo , Proteínas Quinasas Activadas por MitógenosRESUMEN
BACKGROUND: Viaminate, a vitamin A acid drug developed in China, has been clinically used in acne treatment to regulate epithelial cell differentiation and proliferation, inhibit keratinization, reduce sebum secretion, and control immunological and anti-inflammatory actions; however, the exact method by which it works is unknown. METHODS: In the present study, acne was induced in the ears of rats using Propionibacterium acnes combined with sebum application. RESULTS: After 30 days of treatment with viaminate, the symptoms of epidermal thickening and keratin overproduction in the ears of rats were significantly improved. Transcriptomic analysis of rat skin tissues suggested that viaminate significantly regulated the biological pathways of cellular keratinization. Gene differential analysis revealed that the S100A8 and S100A9 genes were significantly downregulated after viaminate treatment. The results of qPCR and Western blotting confirmed that viaminate inhibited the expression of S100A8 and S100A9 genes and proteins in rat and HaCat cell acne models, while its downstream pathway MAPK (MAPK p38/JNK/ERK1/2) protein expression levels were suppressed. Additional administration of the S100A8 and S100A9 complex protein significantly reversed the inhibitory effect of viaminate on abnormal proliferation and keratinization levels in acne cell models. CONCLUSION: In summary, viaminate can improve acne by modulating S100A8 and S100A9 to inhibit MAPK pathway activation and inhibit keratinocyte proliferation and keratinization levels.
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Acné Vulgar , Neoplasias Cutáneas , Ratas , Animales , Humanos , Sistema de Señalización de MAP Quinasas , Células HaCaT/metabolismo , Propionibacterium acnes/metabolismo , Calgranulina B/genética , Calgranulina B/metabolismo , Calgranulina B/farmacología , Tretinoina/metabolismo , Tretinoina/farmacología , Acné Vulgar/tratamiento farmacológico , Diferenciación Celular , Proliferación CelularRESUMEN
Background: Postoperative pneumothorax can lead to additional invasive intervention and extended hospitalization. The effect of initiative pulmonary bullectomy (IPB) during the esophagectomy on preventing postoperative pneumothorax remains controversial. This study evaluated the efficacy and safety of IPB in patients who underwent minimally invasive esophagectomy (MIE) for esophageal carcinoma complicated by ipsilateral pulmonary bullae. Methods: Data from 654 consecutive patients with esophageal carcinoma who underwent MIE from January 2013 to May 2020 were retrospectively collected. A total of 109 patients who had a definite diagnosis of ipsilateral pulmonary bullae were recruited and classified into two groups: the IPB group and the control group (CG). Propensity score matching (PSM, match ratio =1:1), incorporating preoperative clinical features, was used to compare the perioperative complications and analyze efficacy and safety between IPB and control group. Results: The incidences of postoperative pneumothorax in the IPB and control groups was 3.13% and 40.63% respectively, with a significant difference (P<0.001). Logistic analyses indicated that removing ipsilateral bullae was associated with a lower risk (OR 0.030; 95% CI: 0.003-0.338; P=0.005) of incident postoperative pneumothorax. No significant difference was found between the two groups in terms of the incidence of anastomotic leakage (6.25% vs. 3.13%, P=1.000), arrhythmia (3.13% vs. 3.13%, P=1.000), chylothorax (0% vs. 3.13%, P=1.000) and other common complications. Conclusions: In esophageal cancer patients with ipsilateral pulmonary bullae, IPB performed in the same anesthesia process is an effective and safe method for the prevention of postoperative pneumothorax, allowing for a shorter postoperative rehabilitation time, and it does not exert unfavorable effects on complications.
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BACKGROUND: The aim of this study was to evaluate the safety and effectiveness of robot-assisted thymectomy (RAT) in large anterior mediastinal tumors (AMTs) (size ≥6 cm) compared with video-assisted thymectomy (VAT) and open surgery. METHODS: A total of 132 patients with large AMTs who underwent surgical resection from January 2016 to June 2022 were included in this study. A total of 61 patients underwent RAT, 36 patients underwent VAT and 35 patients underwent open surgery. Perioperative outcomes were compared. RESULTS: There were no significant differences in tumor size (p = 0.141), or pathological types (p = 0.903). Compared with the open group, the RAT and VAT groups were associated with a shorter operation time (115.00 vs. 160.00, p = 0.012; 122.50 vs. 160.00, p = 0.071), and less blood loss (50.00 vs. 200.00, p < 0.001; 50.00 vs. 200.00, p < 0.001), respectively. The rate of conversion in the RAT group was similar to that in the VAT group (6.56% vs. 13.89%, p = 0.229). Concomitant resection was less frequently performed in the VAT group than in the RAT and open groups (5.56% vs. 31.15%, p = 0.040; 5.56% vs. 31.43%, p = 0.006). VAT patients had a lower drainage volume (365.00 vs. 700.00 and 910.00 mL, p < 0.001), shorter duration of chest tube (2.00 vs. 3.00 and 4.00, p < 0.001), and shorter hospital stay (5.00 vs. 6.00 and 7.00, p < 0.001) than the RAT and open groups. There was no 30-day mortality in any group. No difference was seen in R0 resection rates (p = 0.846). The postoperative complication rates were similar among the three groups (p = 0.309). Total in-hospital costs (66493.90 vs. 33581.05 and 42876.40, p < 0.001) were significantly higher in the RAT group. CONCLUSIONS: RAT is safe and effective for the resection of large AMTs compared to VAT and open surgery. Vascular resection in RAT is technically feasible. A long-term follow-up is required.
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Neoplasias del Mediastino , Robótica , Timoma , Neoplasias del Timo , Humanos , Neoplasias del Timo/patología , Timoma/patología , Neoplasias del Mediastino/cirugía , Resultado del Tratamiento , Estudios Retrospectivos , Timectomía , Cirugía Torácica Asistida por VideoRESUMEN
Introduction: The role of gut microbiome dysbiosis in the pathogenesis of psoriasis has gained increasing attention in recent years. Secukinumab, targeting interleukin (IL)-17, has a promising efficacy in psoriasis treatment. However, it remains unclear the gut microbiota alteration and related functional changes caused by successful secukinumab therapy in psoriatic patients. Methods: In our study, we compared the fecal microbiome profile between psoriatic patients after secukinumab successful treatment (AT) and the other two groups, psoriatic patients without therapy (BT) and healthy people (H), respectively, by using next-generation sequencing targeting 16S ribosomal RNA. Then, shotgun metagenomic sequencing was first used to characterize bacterial gut microbial communities and related functional changes in the AT group. Results: We found that the diversity and structure of the microbial community in the AT group were significantly changed compared to those in the BT group and the H group. The AT group showed a microbiota profile characterized by increased proportions of the phylum Firmicute, families Ruminococcaceae, and a reduction in the phylum Bacteroidota (elevated F/B ratio). To detect functional alteration, we discovered that secukinumab treatment may construct a more stable homeostasis of the gut microbiome with functional alteration. There were different KEGG pathways, such as the downregulated cardiovascular diseases pathway and the upregulated infectious diseases in the AT group. By metagenomic analysis, the metabolic functional pathway was changed after secukinumab therapy. Discussion: It seems that gut microbiota investigation during biologic drug treatment is useful for predicting the efficacy and risks of drug treatment in disease.
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In recent years, an increasingly more in depth understanding of tumor metabolism in tumorigenesis, tumor growth, metastasis, and prognosis has been achieved. The broad heterogeneity in tumor tissue is the critical factor affecting the outcome of tumor treatment. Metabolic heterogeneity is not only found in tumor cells but also in their surrounding immune and stromal cells; for example, many suppressor cells, such as tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), and tumor-associated T-lymphocytes. Abnormalities in metabolism often lead to short survival or resistance to antitumor therapy, e.g., chemotherapy, radiotherapy, targeted therapy, and immunotherapy. Using the metabolic characteristics of the tumor microenvironment to identify and treat cancer has become a great research hotspot. This review systematically addresses the impacts of metabolism on tumor cells and effector cells and represents recent research advances of metabolic effects on other cells in the tumor microenvironment. Finally, we introduce some applications of metabolic features in clinical oncology.
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Células Supresoras de Origen Mieloide , Neoplasias , Glucosa/metabolismo , Glutamina/metabolismo , Humanos , Metabolismo de los Lípidos , Neoplasias/metabolismo , Microambiente TumoralRESUMEN
Cellular metabolic reprogramming driven by oncogenic mutations is considered as a hallmark in the development of malignant cells, and has been a focus over the past decade. A common theme emerging from these metabolic alterations is that tumor cells can acquire necessary nutrients from a nutrient-limited microenvironment and utilize them to sustain growth and unrestrained cellular division. However, this significant metabolic flexibility and the hostile microenvironment caused by the insufficient vascular exchange, depletion of nutrients, hypoxia, and accumulation of waste products, can inhibit the metabolism and immune activity of tumor-infiltrating lymphocytes and impose barriers to effective antitumor immunotherapies. In this perspective, we review the classical alterations in tumorigenesis- associated metabolic reprogramming and examine the functional contribution of these aberrant metabolisms to the establishment and maintenance of an immunosuppressive microenvironment. Furthermore, we explore the possible approaches to targeting on these metabolic pathways to achieve antitumor immunotherapy, as well as some hypothetical or ongoing combination therapeutic strategies that could, to a certain extent, biologically rationalize and broaden the utility of immune checkpoint inhibitors. Ultimately, we elucidate some dietary modifications that can limit tumor-specific nutritional requirements and maximize the cytotoxicity of other antineoplastic drugs.
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Antineoplásicos , Neoplasias , Humanos , Microambiente Tumoral , Metabolismo Energético , Inmunoterapia , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Factores Inmunológicos/farmacologíaRESUMEN
Investigating the process of gamete formation in plants often requires the use of mutants of selected genes in various genetic backgrounds. For example, analysis of meiotic recombination based on sequencing or genotyping requires the generation of hybrids between two lines. Although T-DNA mutant collections of Arabidopsis thaliana are vast and easily accessible, they are largely confined to Col-0 background. This chapter describes how to efficiently generate knock-out mutants in different Arabidopsis accessions using CRISPR/Cas9 technology. The presented system is based on designing two single-guide RNAs (sgRNAs), which direct the Cas9 endonuclease to generate double-strand breaks at two sites, leading to genomic deletion in targeted gene. The presence of seed-expressed dsRed fluorescence cassette in the CRISPR construct facilitates preselection of genome-edited and transgene-free plants by monitoring the seed fluorescence under the epifluorescent microscope. The protocol provides the detailed information about all steps required to perform genome editing and to obtain loss-of-function mutants in different Arabidopsis accessions within merely two generations.
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Arabidopsis , Arabidopsis/genética , Sistemas CRISPR-Cas/genética , Edición Génica/métodos , Plantas Modificadas Genéticamente/genética , ARN Guía de Kinetoplastida/genética , Semillas/genéticaRESUMEN
Malignant melanoma (MM) recognition in whole-slide images (WSIs) is challenging due to the huge image size of billions of pixels and complex visual characteristics. We propose a novel automatic melanoma recognition method based on the multi-scale features and probability map, named MPMR. First, we introduce the idea of breaking up the WSI into patches to overcome the difficult-to-calculate problem of WSIs with huge sizes. Second, to obtain and visualize the recognition result of MM tissues in WSIs, a probability mapping method is proposed to generate the mask based on predicted categories, confidence probabilities, and location information of patches. Third, considering that the pathological features related to melanoma are at different scales, such as tissue, cell, and nucleus, and to enhance the representation of multi-scale features is important for melanoma recognition, we construct a multi-scale feature fusion architecture by additional branch paths and shortcut connections, which extracts the enriched lesion features from low-level features containing more detail information and high-level features containing more semantic information. Fourth, to improve the extraction feature of the irregular-shaped lesion and focus on essential features, we reconstructed the residual blocks by a deformable convolution and channel attention mechanism, which further reduces information redundancy and noisy features. The experimental results demonstrate that the proposed method outperforms the compared algorithms, and it has a potential for practical applications in clinical diagnosis.