RESUMO
Ten-Eleven-Translocation-2 (Tet2) is a DNA methylcytosine dioxygenase that functions as a tumor suppressor in hematopoietic malignancies. We examined the role of Tet2 in tumor-tissue myeloid cells and found that Tet2 sustains the immunosuppressive function of these cells. We found that Tet2 expression is increased in intratumoral myeloid cells both in mouse models of melanoma and in melanoma patients and that this increased expression is dependent on an IL-1R-MyD88 pathway. Ablation of Tet2 in myeloid cells suppressed melanoma growth in vivo and shifted the immunosuppressive gene expression program in tumor-associated macrophages to a proinflammatory one, with a concomitant reduction of the immunosuppressive function. This resulted in increased numbers of effector T cells in the tumor, and T cell depletion abolished the reduced tumor growth observed upon myeloid-specific deletion of Tet2. Our findings reveal a non-cell-intrinsic, tumor-promoting function for Tet2 and suggest that Tet2 may present a therapeutic target for the treatment of non-hematologic malignancies.
Assuntos
Carcinogênese , Proteínas de Ligação a DNA/metabolismo , Melanoma/imunologia , Células Supressoras Mieloides/imunologia , Proteínas Proto-Oncogênicas/metabolismo , Neoplasias Cutâneas/imunologia , Linfócitos T/imunologia , Animais , Dioxigenases , Feminino , Humanos , Masculino , Melanoma Experimental , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Carga Tumoral , Evasão TumoralRESUMO
Ovule initiation determines the maximum ovule number and has great impact on seed number and yield. However, the regulation of ovule initiation remains largely elusive. We previously reported that most of the ovule primordia initiate asynchronously at floral stage 9 and PINFORMED1 (PIN1) polarization and auxin distribution contributed to this process. Here, we further demonstrate that a small amount of ovule primordia initiate at floral stage 10 when the existing ovules initiated at floral stage 9 start to differentiate. Genetic analysis revealed that the absence of PIN3 function leads to the reduction in pistil size and the lack of late-initiated ovules, suggesting PIN3 promotes the late ovule initiation process and pistil growth. Physiological analysis illustrated that, unlike picloram, exogenous application of NAA can't restore these defective phenotypes, implying that PIN3-mediated polar auxin transport is required for the late ovule initiation and pistil length. qRT-PCR results indicated that the expression of SEEDSTICK (STK) is up-regulated under auxin analogues treatment while is down-regulated in pin3 mutants. Meanwhile, overexpressing STK rescues pin3 phenotypes, suggesting STK participates in PIN3-mediated late ovule initiation possibly by promoting pistil growth. Furthermore, brassinosteroid influences the late ovule initiation through positively regulating PIN3 expression. Collectively, this study demonstrates that PIN3 promotes the late ovule initiation and contributes to the extra ovule number. Our results give important clues for increasing seed number and yield of cruciferous and leguminous crops.
Assuntos
Proteínas de Arabidopsis , Arabidopsis , Proteínas de Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas , Ácidos Indolacéticos/metabolismo , Proteínas de Domínio MADS/genética , Óvulo Vegetal/genéticaRESUMO
Developing efficient, low-cost, MOF catalysts for CO2 conversion at low CO2 concentrations under mild conditions is particularly interesting but remains highly challenging. Herein, we prepared an isostructural series of two-dimensional (2D) multivariate metal-organic frameworks (MTV-MOFs) containing copper- and/or silver-based cyclic trinuclear complexes (Cu-CTC and Ag-CTC). These MTV-MOFs can be used as efficient and reusable heterogeneous catalysts for the cyclization of propargylamine with CO2. The catalytic performance of these MTV-MOFs can be engineered by fine-tuning the Ag/Cu ratio in the framework. Interestingly, the induction of 10% Ag remarkably improved the catalytic efficiency with a turnover frequency (TOF) of 243 h-1, which is 20-fold higher than that of 100% Cu-based MOF (i.e., TOF = 10.8 h-1). More impressively, such a bimetallic MOF still exhibited high catalytic activity even for simulated flue gas with 10% CO2 concentration. Furthermore, the reaction mechanism has been examined through the employment of NMR monitoring experiments and DFT calculations.
RESUMO
Paclitaxel (PTX) is one of the first-line drugs for prostate cancer (PC) treatment. However, the poor water solubility, inadequate specific targeting ability, multidrug resistance, and severe neurotoxicity are far from being fully resolved, despite diverse PTX formulations in the market, such as the gold-standard PTX albumin nanoparticle (Abraxane) and polymer micelles (Genexol-PM). Some studies attempting to solve the multiple problems of chemotherapy delivery fall into the trap of an extremely complicated formulation design and sacrifice druggability. To better address these issues, this study designed an efficient, toxicity-reduced paclitaxel-ginsenoside polymeric micelle (RPM). With the aid of the inherent amphiphilic molecular structure and pharmacological effects of ginsenoside Rg5, the prepared RPM enhances the water solubility and active targeting of PTX, inhibiting chemotherapy resistance in cancer cells. Moreover, the polymeric micelles demonstrated favorable anti-inflammatory and neuroprotective effects, providing ideas for the development of new clinical anti-PC preparations.
Assuntos
Resistencia a Medicamentos Antineoplásicos , Ginsenosídeos , Micelas , Paclitaxel , Ginsenosídeos/química , Ginsenosídeos/farmacologia , Paclitaxel/farmacologia , Paclitaxel/química , Humanos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Animais , Masculino , Camundongos , Linhagem Celular Tumoral , Neoplasias da Próstata/tratamento farmacológico , Portadores de Fármacos/química , Solubilidade , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Sistemas de Liberação de Medicamentos/métodos , Polímeros/químicaRESUMO
Chemical protein synthesis offers a powerful way to access otherwise-difficult-to-obtain proteins such as mirror-image proteins. Although a large number of proteins have been chemically synthesized to date, the acquisition to proteins containing hydrophobic peptide fragments has proven challenging. Here, we describe an approach that combines the removable backbone modification strategy and the peptide hydrazide-based native chemical ligation for the chemical synthesis of a 28 kDa full-length PET degrading enzyme IGGC (a higher depolymerization efficiency of variant leaf-branch compost cutinase (LCC)) containing hydrophobic peptide segments. The synthetic ICCG exhibits the enzymatic activity and will be useful in establishing the corresponding mirror-image version of ICCG.
Assuntos
Polietilenotereftalatos , Hidrolases/química , Fragmentos de Peptídeos , Peptídeos/química , Polietilenotereftalatos/químicaRESUMO
BACKGROUND: Research has suggested significant correlations among ageing, immune microenvironment, inflammation and tumours. However, the relationships among ageing, immune microenvironment, cystitis and bladder urothelial carcinoma (BLCA) in the bladder have rarely been reported. METHODS: Bladder single-cell and transcriptomic data from young and old mice were used for immune landscape analysis. Transcriptome, single-cell and The Cancer Genome Atlas Program datasets of BLCA and interstitial cystitis/bladder pain syndrome (IC/BPS) were used to analyse immune cell infiltration and molecular expression. Bladder tissues from mice, IC/BPS and BLCA were collected to validate the results. RESULTS: Eight types of immune cells (macrophages, B-cells, dendritic cells, T-cells, monocytes, natural killer cells, γδ T-cells and ILC2) were identified in the bladder of mice. Aged mice bladder tissues had a significantly higher number of T-cells, γδ T-cells, ILC2 and B-cells than those in the young group (P < 0.05). Three types of T-cells (NK T-cells, γδ T-cells and naïve T-cells) and three types of B-cells (follicular B-cells, plasma and memory B-cells) were identified in aged mice bladder. Chemokine receptor 7 (CCR7) is highly expressed in aged bladder, IC/BPS and BLCA (P < 0.05). CCR7 is likely to be involved in T- and B-cell infiltration in aged bladder, IC/BPS and BLCA. Interestingly, the high CCR7 expression on BLCA cell membranes was a prognostic protective factor. CONCLUSIONS: In this study, we characterised the expression profiles of immune cells in bladder tissues of aged and young mice and demonstrated that CCR7-mediated T- and B-cell filtration contributes to the development of bladder ageing, IC/BPS and BLCA.
RESUMO
OBJECTIVE: The purpose of this study was to investigate the long-term consequences on the cervical spine after Anterior transcorporeal percutaneous endoscopy cervical discectomy (ATc-PECD) from the biomechanical standpoint. METHODS: A three-dimensional model of the normal cervical spine C2-T1 was established using finite element method. Subsequently, a disc degeneration model and degeneration with surgery model were constructed on the basis of the normal model. The same loading conditions were applied to simulate flexion, extension, lateral bending and axial rotation of the cervical spine. We calculated the cervical range of motion (ROM), intradiscal pressure, and intravertebral body pressure under different motions for observing changes in cervical spine biomechanics after surgery. At the same time, we combined the results of a long-term follow-up of the ATc-PECD, and used imaging methods to measure vertebral and disc height and cervical mobility, the Japanese Orthopaedic Association (JOA) score and visual analog scale (VAS) score were used to assess pain relief and neurological functional recovery. RESULTS: The long-term follow-up results revealed that preoperative JOA score, neck VAS score, hand VAS score, IDH, VBH, and ROM for patients were 9.49 ± 2.16, 6.34 ± 1.68, 5.14 ± 1.48, 5.95 ± 0.22 mm, 15.41 ± 1.68 mm, and 52.46 ± 9.36° respectively. It changed to 15.71 ± 1.13 (P < 0.05), 1.02 ± 0.82 (P < 0.05), 0.77 ± 0.76 (P < 0.05), 4.73 ± 0.26 mm (P < 0.05), 13.67 ± 1.48 mm (P < 0.05), and 59.26 ± 6.72° (P < 0.05), respectively, at 6 years postoperatively. Finite element analysis showed that after establishing the cervical spondylosis model, the overall motion range for flexion, extension, lateral bending, and rotation decreased by 3.298°, 0.753°, 3.852°, and 1.131° respectively. Conversely, after establishing the bone tunnel model, the motion range for these actions increased by 0.843°, 0.65°, 0.278°, and 0.488° respectively, consistent with the follow-up results. Moreover, analysis of segmental motion changes revealed that the increased cervical spine mobility was primarily contributed by the surgical model segments. Additionally, the finite element model demonstrated that bone tunneling could lead to increased stress within the vertebral bodies and intervertebral discs of the surgical segments. CONCLUSIONS: Long-term follow-up studies have shown that ATc-PECD has good clinical efficacy and that ATc-PECD can be used as a complementary method for CDH treatment. The FEM demonstrated that ATc-PECD can lead to increased internal stresses in the vertebral body and intervertebral discs of the operated segments, which is directly related to cervical spine degeneration after ATc-PECD.
Assuntos
Vértebras Cervicais , Discotomia Percutânea , Endoscopia , Análise de Elementos Finitos , Deslocamento do Disco Intervertebral , Amplitude de Movimento Articular , Humanos , Vértebras Cervicais/cirurgia , Vértebras Cervicais/diagnóstico por imagem , Deslocamento do Disco Intervertebral/cirurgia , Deslocamento do Disco Intervertebral/fisiopatologia , Deslocamento do Disco Intervertebral/diagnóstico por imagem , Seguimentos , Discotomia Percutânea/métodos , Endoscopia/métodos , Masculino , Pessoa de Meia-Idade , Adulto , Feminino , Descompressão Cirúrgica/métodos , Resultado do Tratamento , Fenômenos Biomecânicos , Degeneração do Disco Intervertebral/cirurgia , Degeneração do Disco Intervertebral/diagnóstico por imagemRESUMO
In the process of murder investigation, it is of great significance to find the discarded and buried human remains accurately. The main methods of searching for human remains include human visual search, aerial detection, geophysical technology, remote imaging technology and canine olfactory search technique. Canine olfactory search for human remains is a recognized time-effective and non-invasive search method, making dogs the most valuable search tool in forensic investigation. By systematically reviewing and summarizing relevant literature, and based on the theory of volatile organic compound produced by the decomposition of human remains, this paper explores the basic principle of the canine olfactory search technique for human remains. This paper also reviews the application of training canine search technique for human remains in forensic investigation by using human blood, tissue, cadaver putrefying fluid and odor substitutes as sniffing sources. The application prospect of canine olfactory search for human remains was prospected from the perspectives of detection of volatile organic compound during cadaver decay, development of odor substitutes and adsorption devices, and technology tactics used in canine training and use, to provide references for the relevant research of canine olfactory search for human remains in China.
Assuntos
Odorantes , Olfato , Compostos Orgânicos Voláteis , Cães , Animais , Humanos , Olfato/fisiologia , Odorantes/análise , Compostos Orgânicos Voláteis/análise , Mudanças Depois da Morte , Restos Mortais , Ciências Forenses/métodos , Cadáver , Medicina Legal/métodosRESUMO
D-peptide ligands can be screened for therapeutic potency and enzymatic stability using synthetic mirror-image proteins (D-proteins), but efficient acquisition of these D-proteins can be hampered by the need to accomplish their in vitro folding, which often requires the formation of correctly linked disulfide bonds. Here, we report the finding that temporary installation of natural O-linked-ß-N-acetyl-D-glucosamine (O-GlcNAc) groups onto selected D-serine or D-threonine residues of the synthetic disulfide-bonded D-proteins can facilitate their folding in vitro, and that the natural glycosyl groups can be completely removed from the folded D-proteins to afford the desired chirally inverted D-protein targets using naturally occurring O-GlcNAcase. This approach enabled the efficient chemical syntheses of several important but difficult-to-fold D-proteins incorporating disulfide bonds including the mirror-image tumor necrosis factor alpha (D-TNFα) homotrimer and the mirror-image receptor-binding domain of the Omicron spike protein (D-RBD). Our work establishes the use of O-GlcNAc to facilitate D-protein synthesis and folding and proves that D-proteins bearing O-GlcNAc can be good substrates for naturally occurring O-GlcNAcase.
Assuntos
Acetilglucosaminidase , Proteínas , Peptídeos , Polissacarídeos , GlucosaminaRESUMO
Mirror-image proteins (D-proteins) are useful in biomedical research for purposes such as mirror-image screening for D-peptide drug discovery, but the chemical synthesis of many D-proteins is often low yielding due to the poor solubility or aggregation of their constituent peptide segments. Here, we report a Lys-C protease-cleavable solubilizing tag and its use to synthesize difficult-to-obtain D-proteins. Our tag is easily installed onto multiple amino acids such as DLys, DSer, DThr, and/or the N-terminal amino acid of hydrophobic D-peptides, is impervious to various reaction conditions, such as peptide synthesis, ligation, desulfurization, and transition metal-mediated deprotection, and yet can be completely removed by Lys-C protease under denaturing conditions to give the desired D-protein. The efficacy and practicality of the new method were exemplified in the synthesis of two challenging D-proteins: D-enantiomers of programmed cell death protein 1 IgV domain and SARS-CoV-2 envelope protein, in high yield. This work demonstrates that the enzymatic cleavage of solubilizing tags under denaturing conditions is feasible, thus paving the way for the production of more D-proteins.
Assuntos
Peptídeos , Proteínas , Proteínas/química , Peptídeos/química , Aminoácidos/química , Técnicas de Química Sintética/métodos , Peptídeo Hidrolases , EndopeptidasesRESUMO
Interfacial charge transfer on the surface of heterogeneous photocatalysts dictates the efficiency of reactive oxygen species (ROS) generation and therefore the efficiency of aerobic oxidation reactions. Reticular chemistry in metal-organic frameworks (MOFs) allows for the rational design of donor-acceptor pairs to optimize interfacial charge-transfer kinetics. Herein, we report a series of isostructural fcu-topology Ni8-MOFs (termed JNU-212, JNU-213, JNU-214, and JNU-215) with linearly bridged bipyrazoles as organic linkers. These crystalline Ni8-MOFs can maintain their structural integrity in 7 M NaOH at 100 °C for 24 h. Experimental studies reveal that linker engineering by tuning the electron-accepting capacity of the pyrazole-bridging units renders these Ni8-MOFs with significantly improved charge separation and transfer efficiency under visible-light irradiation. Among them, the one containing a benzoselenadiazole unit (JNU-214) exhibits the best photocatalytic performance in the aerobic oxidation of benzylamines with a conversion rate of 99% in 24 h. Recycling experiments were carried out to confirm the stability and reusability of JNU-214 as a robust heterogeneous catalyst. Significantly, the systematic modulation of the electron-accepting capacity of the bridging units in donor-acceptor-donor MOFs provides a new pathway to develop viable noble-metal-free heterogeneous photocatalysts for aerobic oxidation reactions.
RESUMO
BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is an immunologically and histologically diverse tumor. However, how the structural heterogeneity of tumor microenvironment (TME) affects cancer progression and treatment response remains unclear. Hence, we characterized the TME architectures of ccRCC tissues using imaging mass cytometry (IMC) and explored their associations with clinical outcome and therapeutic response. METHODS: Using IMC, we profiled the TME landscape of ccRCC and paracancerous tissue by measuring 17 markers involved in tissue architecture, immune cell and immune activation. In the ccRCC tissue, we identified distinct immune architectures of ccRCC tissue based on the mix score and performed cellular neighborhood (CN) analysis to subdivide TME phenotypes. Moreover, we assessed the relationship between the different TME phenotypes and ccRCC patient survival, clinical features and treatment response. RESULTS: We found that ccRCC tissues had higher levels of CD8+ T cells, CD163- macrophages, Treg cells, endothelial cells, and fibroblasts than paracancerous tissues. Immune infiltrates in ccRCC tissues distinctly showed clustered and scattered patterns. Within the clustered pattern, we identified two subtypes with different clinical outcomes based on CN analysis. The TLS-like phenotype had cell communities resembling tertiary lymphoid structures, characterized by cell-cell interactions of CD8+ T cells-B cells and GZMB+CD8+ T cells-B cells, which exhibited anti-tumor features and favorable outcomes, while the Macrophage/T-clustered phenotype with macrophage- or T cell-dominated cell communities had a poor prognosis. Patients with scattered immune architecture could be further divided into scattered-CN-hot and scattered-CN-cold phenotypes based on the presence or absence of immune CNs, but both had a better prognosis than the macrophage/T-clustered phenotype. We further analyzed the relationship between the TME phenotypes and treatment response in five metastatic ccRCC patients treated with sunitinib, and found that all three responders were scattered-CN-hot phenotype while both non-responders were macrophage/T-clustered phenotype. CONCLUSION: Our study revealed the structural heterogeneity of TME in ccRCC and its impact on clinical outcome and personalized treatment. These findings highlight the potential of IMC and CN analysis for characterizing TME structural units in cancer research.
Assuntos
Carcinoma de Células Renais , Carcinoma , Neoplasias Renais , Humanos , Linfócitos T CD8-Positivos , Células Endoteliais , Microambiente Tumoral , PrognósticoRESUMO
Forensic DNA analysis of semen-vaginal fluid mixed stains is essential and necessary in sexual assault cases. Here, we used a magnetic bead conjugated acrosin binding protein (ACRBP) antibody to separate and enrich sperm cells from mixed stains. Previously, western blotting indicated that ACRBP was specifically expressed in sperm cells, but not in female blood and epithelial cells, while immunofluorescence data showed ACRBP was localized to the acrosome in sperm cells. In our study, sperm were separated from mixed samples at three sperm cell/female buccal epithelial cell ratios (103:103; 103:104; and 103:105) using a magnetic bead conjugated ACRBP antibody. Subsequently, 23 autosomal short tandem repeat (STR) loci were amplified using the Huaxia™ Platinum PCR Amplification System and genotyped using capillary electrophoresis. The genotyping success rate for STR loci was 90% when the sperm to female buccal epithelial cell ratio was > 1:100 in mixed samples. Our results suggest that the magnetic bead conjugated ACRBP antibody is effective for isolating sperm cells in sexual assault cases.
Assuntos
Corantes , Sêmen , Masculino , Humanos , Feminino , Corantes/metabolismo , Espermatozoides , Coloração e Rotulagem , Fenômenos Magnéticos , Impressões Digitais de DNA/métodosRESUMO
Herein we report two tubular metal-organic cages (MOCs), synthesized by the self-assembly of bidentate metalloligands with different lengths and PdII. These two MOCs feature Pd4L8-type square tubular and Pd3L6-type triangular cage structures, respectively. Both MOCs have been fully characterized by NMR spectroscopy, mass spectrometry, and theoretical calculation. Both cages can be employed for encapsulating polycyclic aromatic hydrocarbons and show high binding affinity toward coronene.
RESUMO
Single-emission luminescence sensors are less than satisfactory for complex systems due to their susceptibility to environmental disturbances. Lanthanum-based metal-organic frameworks (Ln-MOFs) with highly stable ratiometric dual-emission are regarded as promising luminescence probes owing to their fascinating ligand-to-metal energy transfer behaviors (also known as the antenna effect). Herein, we report the synthesis of a pair of isostructural europium-based MOFs (termed JNU-219 and JNU-220) by utilizing two X-shaped tetracarboxylate linkers, 4,4',4â³,4â´-benzene-2,3,5,6-tetrayl-tetrabenzoate (BTEB) and 4,4',4â³,4â´-pyrazine-2,3,5,6-tetrayl-tetrabenzoate (BTTB). Both JNU-219 and JNU-220 present the characteristic red luminescence of Eu3+, yet the pyrazine functionalization of the BTTB linker renders JNU-220 with significantly increased luminescence emission, almost 30 times that of JNU-219. As a result, the detection limit of JNU-220 for the ratiometric luminescence sensing of PO43- was determined to be as low as 0.22 µM, which is far superior to those of other reported MOF materials. Additionally, we demonstrate the excellent stability and reusability of JNU-220, further verifying its potential as a robust ratiometric luminescence probe.
RESUMO
BACKGROUND: The current treatments for adjacent two-segment cervical spondylotic myelopathy (CSM) include two-segment anterior cervical discectomy and fusion (ACDF) and single-segment anterior cervical corpectomy and fusion (ACCF). Long-term follow-up has demonstrated that both procedures have complications such as reduced cervical mobility, accelerated degeneration of adjacent segments and loosening of internal fixation screws. The purpose of this study is to demonstrate the feasibility, safety, and efficacy of anterior percutaneous full-endoscopic transcorporeal decompression of the spinal cord (APFETDSC) via one vertebra with two bony channels for the treatment of adjacent two-segment CSM and to present our surgical experience. METHODS: Anterior percutaneous full-endoscopic transcorporeal decompression of the spinal cord (APFETDSC) via one vertebra with two bony channels was performed for 12 patients with adjacent two-segment CSM with follow-up care for at least 12 months. The Visual analog scale (VAS) and the Japanese Orthopedic Association Score (JOA) were recorded, and modified Macnab criteria were used to evaluate the treatment excellence rate. Radiological examinations, including X-ray, computed tomography (CT) and magnetic resonance imaging (MRI), were used to evaluate spinal cord decompression, intervertebral stability and healing of the bony channel. RESULTS: All 12 patients completed the operation successfully. No postoperative complications, such as dysphagia, Horner's syndrome, or laryngeal recurrent nerve palsy, were found. The postoperative VAS and JOA scores were significantly improved compared with those before surgery(P < 0.001). According to the modified Macnab criteria, the clinical outcome was excellent in 8 cases, good in 3 cases and fine in 1 case at the final follow-up and the excellent and good rate was 91.7%. Postoperative and follow-up imaging showed significant spinal cord decompression, well-healed bony channels and no cervical instability. CONCLUSIONS: This study is the first report of anterior percutaneous full-endoscopic transcorporeal decompression of the spinal cord via one vertebra with two bony channels. This procedure has the advantages of less trauma, faster recovery, fewer complications and no need to implant internal fixators. This is a minimally invasive, feasible and safe surgical procedure for patients with adjacent two-segment CSM.
Assuntos
Doenças da Medula Espinal , Fusão Vertebral , Espondilose , Humanos , Resultado do Tratamento , Doenças da Medula Espinal/cirurgia , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Discotomia , Descompressão Cirúrgica/métodos , Estudos Retrospectivos , Espondilose/diagnóstico por imagem , Espondilose/cirurgiaRESUMO
BACKGROUND: Minimally invasive modifications of inguinal lymphadenectomy (IL), including laparoscopic IL (LIL) and robotic-assisted IL (RAIL), have been utilized for penile cancer. Comparative study is necessary to guide the decision about which minimally invasive technique to select for IL. Therefore we compared RAIL with LIL performed via an antegrade approach in terms of perioperative outcomes. METHODS: We conducted a retrospective study of 43 patients who underwent RAIL (n = 20) or LIL (n = 23) for penile cancer from 2016 to 2020. The key surgical procedures and techniques are described. Complications were graded by the Clavien-Dindo classification, and operative time, estimated blood loss (EBL), lymph nodal yield, nodal positivity, postoperative drain duration, and disease recurrence during follow-up were assessed. Categorical variables were compared using chi-squared whereas continuous variables were compared by t-tests. RESULTS: The operative time for RAIL was significantly shorter than that of LIL (median 83 vs 95 min). Significantly less blood loss was reported with RAIL than with LIL (median 10 vs 35 ml). Lymph node yield, pathological positive nodes, the hospital stay, postoperative drain duration, postoperative complications and recurrence were similar for RAIL and LIL. CONCLUSIONS: For patients with penile cancer, perioperative outcomes of RAIL and LIL were similar, but there was less blood loss, a shorter operative time for robotic cases.
Assuntos
Laparoscopia , Neoplasias Penianas , Procedimentos Cirúrgicos Robóticos , Masculino , Humanos , Procedimentos Cirúrgicos Robóticos/métodos , Neoplasias Penianas/cirurgia , Estudos Retrospectivos , Recidiva Local de Neoplasia/cirurgia , Excisão de Linfonodo/métodos , Laparoscopia/métodosRESUMO
The prevalence of antibiotic resistance genes (ARGs) in diverse habitats threatens public health. Watersheds represent critical freshwater ecosystems that interact with both the soil and atmosphere. However, a holistic understanding of ARGs distribution across these environmental media is currently inadequate. We profiled ARGs and bacterial communities in air-water-soil in the same watershed area during four seasons using high-throughput qPCR and 16S rRNA gene sequencing. Our findings demonstrated that aminoglycoside resistance genes (58.5%) were dominant in water, and multidrug resistance genes (55.2% and 54.2%) were dominant in soil and air. Five ARGs and nineteen bacterial genera were consistently detected in all samples, were named as shared genes or bacteria. Co-occurrence Network analysis revealed the co-occurrence module of resistance genes, mobile genetic elements (MGEs), and potential bacterial hosts, indicating that shared genes and bacteria may persist and co-spread across different environmental media. The risk assessment framework, based on ARGs' abundance, detection rate, and mobility, identified 33 high-risk ARGs. This is essential to evaluate the health risks of ARGs and to develop strategies to limit the threat of antibiotic resistance. Our study offers new insights into the risks associated with ARGs in the environment and suggests that ARGs may depend on specific bacterial cohabitants that co-exist with MGEs to facilitate their spread across environmental interfaces.
Assuntos
Água Potável , Genes Bacterianos , Solo , Antibacterianos/farmacologia , Ecossistema , RNA Ribossômico 16S/genética , Resistência Microbiana a Medicamentos/genética , Bactérias/genéticaRESUMO
This study aims to explore the effect of Buyang Huanwu Decoction glycosides on the inflammatory response of apolipoprotein E~(-/-)(ApoE~(-/-)) mice and RAW264.7 cells through nuclear factor kappa-B(NF-κB) signaling pathway. In the in vivo experiment, ApoE~(-/-) mice were fed with high-fat diets for 12 weeks to induce the animal model of atherosclerosis, and 75 µg·mL~(-1) oxidized low-density lipoprotein(Ox-LDL) incubated RAW264.7 cells for 24 h to establish the atherosclerosis cell model. Automatic biochemical analyzer, hematoxylin-eosin(HE) staining, enzyme-linked immunosorbent assay(ELISA), Western blot, and droplet digital polymerase chain reaction(PCR) were used to determine the blood lipid levels, aortic intimal thickness, inflammatory factor content, NF-κB pathway-related proteins, and mRNA expression levels, and evaluate arterial atherosclerotic lesions and anti-atherosclerotic mechanisms of the drug. The model of atherosclerosis was successfully established in ApoE~(-/-) mice after 12 weeks of feeding with high-fat diets. In the model group, the plasma levels of total cholesterol(TC), triglyceride(TG), and low-density lipoprotein cholesterol(LDL-C) were increased(P<0.01), the intima of the blood vessels was thickened, the levels of inflammatory factors tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) were increased, and the protein and mRNA expressions of NF-κB and inhibitor of NF-κB(IκBα) were significantly increased as compared with the control group. Compared with the model group, the high-dose Buyang Huanwu Decoction glycoside group decreased the plasma levels of TC, TG, and LDL-C, reduced the plaque area and thickness and the content of inflammatory factor TNF-α, and inhibited the protein and mRNA expressions of NF-κB and IκBα, with the effect same as Buyang Huanwu Decoction. In the in vivo experiment, 75 µg·mL~(-1) Ox-LDL stimulated RAW264.7 cells for 24 h to successfully establish a foam cell model. As compared with the control group, the nuclear amount of NF-κB and the protein and mRNA expressions of IκBα in the model group increased. Compared with the model group, the middle-dose and high-dose Buyang Huanwu Decoction glycoside groups decreased the nuclear amount of NF-κB and the protein and mRNA expressions of IκBα. The above results show that the glycosides are the main effective substances of Buyang Huanwu Decoction against atherosclerosis, which inhibit the NF-κB pathway and reduce the inflammatory response, thus playing the role against atherosclerotic inflammation same as Buyang Huanwu Decoction.
Assuntos
Aterosclerose , NF-kappa B , Camundongos , Animais , NF-kappa B/genética , NF-kappa B/metabolismo , Inibidor de NF-kappaB alfa/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Glicosídeos/farmacologia , LDL-Colesterol , Aterosclerose/tratamento farmacológico , Aterosclerose/genética , Transdução de Sinais , Inflamação/tratamento farmacológico , Interleucina-6 , Apolipoproteínas E/genética , Apolipoproteínas E/farmacologia , RNA Mensageiro/metabolismoRESUMO
Post-synthetic modification (PSM) is an effective approach for the tailored functionalization of metal-organic architectures, but its generalizability remains challenging. Herein we report a general covalent PSM strategy to functionalize Pdn L2n metal-organic cages (MOCs, n=2, 12) through an efficient Diels-Alder cycloaddition between peripheral anthracene substituents and various functional motifs bearing a maleimide group. As expected, the solubility of functionalized Pd12 L24 in common solvents can be greatly improved. Interestingly, concentration-dependent circular dichroism and aggregation-induced emission are achieved with chiral binaphthol (BINOL)- and tetraphenylethylene-modified Pd12 L24 , respectively. Furthermore, Pd12 L24 can be introduced with two different functional groups (e.g., chiral BINOL and achiral pyrene) through a step-by-step PSM route to obtain chirality-induced circularly polarized luminescence. Moreover, similar results are readily observed with a smaller Pd2 L4 system.