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Despite its significant potential in various disease treatments and diagnostics, microbiotherapy is consistently plagued by multiple limitations ranging from manufacturing challenges to in vivo functionality. Inspired by the strategy involving nonproliferating yet metabolically active microorganisms, we report an intracellular gelation approach that can generate a synthetic polymer network within bacterial cells to solve these challenges. Specifically, poly(ethylene glycol dimethacrylate) (PEGDA, 700 Da) monomers are introduced into the bacterial cytosol through a single cycle of freeze-thawing followed by the initiation of intracellular free radical polymerization by UV light to create a macromolecular PEGDA gel within the bacterial cytosol. The molecular crowding resulting from intracytoplasmic gelation prohibits bacterial division and confers robust resistance to simulated gastrointestinal fluids and bile acids while retaining the ability to secrete functional proteins. Biocompatibility assessments demonstrate that the nondividing gelatinized bacteria are effective in alleviating systemic inflammation triggered by intravenous Escherichia coli injection. Furthermore, the therapeutic efficacy of gelatinized Lactobacillus rhamnosus in colitis mice provides additional support for this approach. Collectively, intracellular gelation indicates a universal strategy to manufacture next-generation live biotherapeutics for advanced microbiotherapy.
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Escherichia coli , Polietilenoglicóis , Animais , Camundongos , Escherichia coli/efeitos dos fármacos , Polietilenoglicóis/química , Géis/química , Modelos Animais de Doenças , Colite/tratamento farmacológico , Colite/induzido quimicamente , Metacrilatos/químicaRESUMO
BACKGROUND: More and more studies have demonstrated that potassium channel tetramerization domain-containing 5 (KCTD5) plays an important role in the development of cancer, but there is a lack of comprehensive research on the biological function of this protein in pan-cancer. This study systematically analyzed the expression landscape of KCTD5 in terms of its correlations with tumor prognosis, the immune microenvironment, programmed cell death, and drug sensitivity. METHODS: We investigated a number of databases, including TCGA, GEPIA2, HPA, TISIDB, PrognoScan, GSCA, CellMiner, and TIMER2.0. The study evaluated the expression of KCTD5 in human tumors, as well as its prognostic value and its association with genomic alterations, the immune microenvironment, tumor-associated fibroblasts, functional enrichment analysis, and anticancer drug sensitivity. Real-time quantitative PCR and flow cytometry analysis were performed to determine the biological functions of KCTD5 in lung adenocarcinoma cells. RESULTS: The results indicated that KCTD5 is highly expressed in most cancers and that its expression is significantly correlated with tumor prognosis. Moreover, KCTD5 expression was related to the immune microenvironment, infiltration by cancer-associated fibroblasts, and the expression of immune-related genes. Functional enrichment analysis revealed that KCTD5 is associated with apoptosis, necroptosis, and other types of programmed cell death. In vitro experiments showed that knockdown of KCTD5 promoted apoptosis of A549 cells. Correlation analysis confirmed that KCTD5 was positively correlated with the expression of the anti-apoptotic genes Bcl-xL and Mcl-1. Additionally, KCTD5 was significantly associated with sensitivity to multiple antitumor drugs. CONCLUSION: Our results suggest that KCTD5 is a potential molecular biomarker that can be used to predict patient prognosis, immunoreactions and drug sensitivity in pan-cancer. KCTD5 plays an important role in regulating programmed cell death, especially apoptosis.
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Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Biomarcadores Tumorais/genética , Apoptose/genética , Células A549 , Prognóstico , Microambiente Tumoral/genética , Canais de PotássioRESUMO
The present study was conducted to investigate the molecular mechanism of propofol in inhibiting the proliferation of mouse cardiac fibroblasts (CFs) induced by angiotensin II (Ag II). The ventricles of SPF mice from Kunming were cultured for the second to third generation of CFs under aseptic condition. On the basis of the different adding conditions, the mice were divided into five groups: (1) control group: no drug were added; (2) Ag II group: 100 nmol/L Ag II were added; (3) 10 µmol/L propofol + 100 nmol/L Ag II group; (4) 30 µmol/L propofol + 100 nmol/L Ag II group; (5) 50 µmol/L propofol + 100 nmol/L Ag II group. The effects of propofol on the proliferation of CFs induced by Ag II, the expression of CFs ET-1, the activity of NADPH oxidase and the formation of ROS were analyzed. In addition, our study also explored the potential role of Akt-eNOS-nitric oxide pathway regarding the inhibition of proliferation of Ag II induced CFs by propofol. We found that the proliferation of CFs, the secretion of ET-1, the activity of NADPH oxidase and the level of intracellular ROS and fibronectin expression were significantly increased after CFs exposure to Ag II for 24 h. The abovementioned indexes decreased significantly in CFs after treated with propofol for 24 h (10, 30, or 50 µmol/L) with significant statistical difference (P < 0.05). Akt and eNOS siRNA transfection significantly decreased the levels of Akt and eNOS protein, respectively. Blocking pathway of Akt-eNOS-nitric oxide decreased the inhibitory effect of propofol on Ag II-induced cell proliferation of CFs. Propofol exerts effect in inhibiting ET-1 and fibronectin expression and the formation of ROS induced by Ag II. Moreover, Akt-eNOS-nitric oxide signaling pathway may be involved in the effect of propofol on the proliferation of CFs induced by Ag II.
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Endotelina-1/metabolismo , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Propofol/metabolismo , Propofol/farmacologia , Angiotensina II/farmacologia , Animais , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Fibronectinas/metabolismo , Camundongos , Miocárdio/metabolismo , NADPH Oxidases/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Organismos Livres de Patógenos EspecíficosRESUMO
The radiative characteristics of char and ash in the pulverized coal furnace at the wavelength of 560 nm are analyzed here. The particles' radiative coefficients are calculated in the exit of the burner and in the upper part of the furnace separately according to the Mie theory. It can be inferred that in the exit of the burner, char has a great effect on the particles' radiative coefficient, which accounts for a percentage of 90%. While in the upper of the furnace, ash dominates the particles' radiative coefficient. The scattering ratio of the ash is calculated to be 91.6 and the scattering ratio of the char is only 50%.
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Our daily life is disturbed seriously by the haze weather now. It is very important to measure the haze composition quantificationally. The main composition of haze is SO(2), NO(2) and particles. At present, the research of measuring gas and particle simultaneously is rare relatively. This paper use differential optical absorption spectroscopy (DOAS) to simulate the concentration measurement of gas and particle simultaneously and obtain some meaningful results. Absorption spectral of many groups of different concentration of SO(2), NO(2) and particle were simulated, and each concentration was inverted by DOAS. In the first group of single component, the concentration change from 100 to 1 000 ppm, the inverted error of SO(2) is not greater than 0.17%, and which is 0.64% for NO(2). When the diameter of particle change from 100 to 500 nm, the inverted error is not greater than 2.08%. In the second group of multiple gases, when the concentration ratio of SO(2) and NO(2) is at the range of 1 : 10 and 5 : 1, the error of SO(2) is not bigger than 8%, and 5% for NO(2), relatively. But when the concentration of SO(2) is 10 times than NO(2), the error is higher than 10% for NO(2). In the third group of gas and particle, the error of gas concentration is lower than 10%, but the concentration error of particle is depended on signal to noise ratio (SNR) greatly. When SNR is higher than 40 dB, error can lower than 10% and when SNR is lower than 30dB, the error is bigger than 20%. From these results, we can see that DOAS can measurement SO(2), NO(2) and particles simultaneously effectively, and can applied to measure and analyze haze composition. However, when the absorption strength of the gases is different greatly, the strong absorption gas influent the weak absorption gas largely. And the SNR is lower, the error of inverted particle concentration increased greatly. The solution of these problems need better filtering and noise reduction method.
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To obtain the weaker second harmonic signal of low concentration, reduce the minimum measurable limit and improve the sensitivity and accuracy of absorption measurement, a serious of data processing methods are proposed based on tunable diode laser wavelength modulation spectroscopy. The experiment on lower NH3 concentration at 2.25 µm was carried out in a 10.13 m absorption cell with different concentration. The peak height of the second harmonic signal is maximum at m=2.2, which optimizes the signal-to-noise ratio. In order to guarantee the optimal signal-to-noise ratio, the experiment was carried out by loading the optimal high frequency modulation signal. WMS-2f was performed at a repetitive scan rate of 200 Hz and a current-modulation rate of 15 kHz, wavelength modulation spectroscopy with the optimal signal-to-noise ratio was adopted for its better noise immunity to measure different lower NH3 concentration in the Herriott cell. This survey is focused on the ν2+ν3 bands of absorption spectra near 2.25 µm in near-infrared region at ambient temperature and pressure, the line strengths of 2.25 µm are much larger than the absorption lines in the telecommunication bands, using stronger NH3 absorption lines can offer the potential of lower detection limits. During the data processing, the background signal of the original harmonic should be deducted at first, the second harmonic signal of 0.6×10-6 was obtained in a 10 m long-path Herriott cell after data processing, these signal processing mainly consist of cross-correlation analysis, multiple averages and wavelet transform analysis, the cross-correlation analysis was used to control the shift of center wavelength, the multiple averages and wavelet transform analysis were used to reduce influences of the environment noise, after that we get the revised second harmonic signal and improve the accuracy of the measurement results. The experimental results show that these data processing methods can obviously improve the signal quality and reduce the minimum measurable limit about 100 times lower than before. The experiment doesn't need to add any laboratory equipment and can well restrain the influence of the environmental noise and other disturbance, so these signal process combined with wavelength modulation technique will be more useful for on-line gas detection technology.
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The two-dimensional concentration distribution was reconstructed by using algebraic iterative reconstruction algorithm. This paper mainly focused on the effects of multispectral H2O absorptions on condition that the laser beam was less and the temperature was known, i.e. the influence of temperature on spectral line-strength was not considered as to this concentration distribution. Based on ART algorithm, increased spectral lines and increased laser beam were compared under the same concentration model. Three H2O lines were selected to reconstruct two-dimensional distribution of non-uniform gas concentration, and these three transitions were selected within the external cavity diode laser turning range in the simulated system. The interested region was discretized to 10×10 grid points, and the temperature and concentration of the reconstruction model were not evenly distributed, so the unimodal distribution and bimodal distribution were used to describe the concentration distribution. The simulated system also calculated the effective utilization of laser beams and absorption lines. The results showed that the reconstruction quality quickly increased with increasing H2O absorption lines when the laser beams were very few, the increased absorption lines could get more spectral information related to the concentration. The increased laser beam is also effective to improve the accuracy of reconstruction results, but increasing the absorption lines can better reconstruct a two-dimensional concentration distribution. Improving the absorption lines can also effectively reduce the costs of the hardware and the complexity of the measurement system, which shows that the multispectral absorption lines are applicable to in-situ measurements.
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For decades, digoxin has been widely used to control ventricular rate in atrial fibrillation (AF). However, it remains controversial as to whether digoxin is associated with increased mortality in AF. In this study, we searched relevant studies that were published before December 1, 2014, in PubMed, EMBASE, and the Cochrane central databases. We systematically reviewed the references and performed a meta-analysis of 8 carefully selected studies with 302,738 patients who were included for the final analysis. It was shown that digoxin use was associated with increased risk of all-cause mortality in AF overall [hazard ratio (HR) = 1.375, 95% confidence intervals (CI), 1.201-1.574, P = 0.0001]. Subgroup analysis further revealed that digoxin was associated with increased all-cause mortality in patients with AF, which was complicated by heart failure (HF) (HR = 1.201, CI, 1.074- 1.344, P = 0.001), and in those subjects without HF (HR = 1.172, CI, 1.148-1.198, P = 0.0001). Sensitivity analyses found results to be robust. Our findings indicated that digoxin use was associated with significantly increased all-cause mortality in patients with AF regardless of concomitant HF. We suggest that digoxin should not be preferentially used over other rate control medications in AF.
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Antiarrítmicos/efeitos adversos , Fibrilação Atrial/mortalidade , Digoxina/efeitos adversos , Insuficiência Cardíaca/mortalidade , Antiarrítmicos/administração & dosagem , Antiarrítmicos/uso terapêutico , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Interpretação Estatística de Dados , Bases de Dados Factuais , Digoxina/administração & dosagem , Digoxina/uso terapêutico , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Mortalidade/tendênciasRESUMO
Polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) are key pollutants in waste incineration. At present, incinerator managers and official supervisors focus only on emissions evolving during steady-state operation. Yet, these emissions may considerably be raised during periods of poor combustion, plant shutdown, and especially when starting-up from cold. Until now there were no data on transient emissions from medical (or hospital) waste incineration (MWI). However, MWI is reputed to engender higher emissions than those from municipal solid waste incineration (MSWI). The emission levels in this study recorded for shutdown and start-up, however, were significantly higher: 483 ± 184 ng Nm(-3) (1.47 ± 0.17 ng I-TEQ Nm(-3)) for shutdown and 735 ng Nm(-3) (7.73 ng I-TEQ Nm(-3)) for start-up conditions, respectively. Thus, the average (I-TEQ) concentration during shutdown is 2.6 (3.8) times higher than the average concentration during normal operation, and the average (I-TEQ) concentration during start-up is 4.0 (almost 20) times higher. So monitoring should cover the entire incineration cycle, including start-up, operation and shutdown, rather than optimised operation only. This suggestion is important for medical waste incinerators, as these facilities frequently start up and shut down, because of their small size, or of lacking waste supply. Forthcoming operation should shift towards much longer operating cycles, i.e., a single weekly start-up and shutdown.
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Poluentes Atmosféricos/análise , Dioxinas/análise , Resíduos de Serviços de Saúde/análise , China , Dioxinas/química , Monitoramento Ambiental , IncineraçãoRESUMO
In order to on-line measure the trace ammonia slip of the commercial power plant in the future, this research seeks to measure the trace ammonia by using tunable diode laser absorption spectroscopy under ambient temperature and pressure, and at different temperatures, and the measuring temperature is about 650 K in the power plant. In recent years lasers have become commercially available in the near-infrared where the transitions are much stronger, and ammonia's spectroscopy is pretty complicated and the overlapping lines are difficult to resolve. A group of ammonia transitions near 4 433.5 cm(-1) in the v2 +v3 combination band have been thoroughly selected for detecting lower concentration by analyzing its absorption characteristic and considering other absorption interference in combustion gases where H2O and CO2 mole fraction are very large. To illustrate the potential for NH3 concentration measurements, predictions for NH3, H2O and CO2 are simultaneously simulated, NH3 absorption lines near 4 433.5 cm(-1) wavelength meet weaker H2O absorption than the commercial NH3 lines, and there is almost no CO2 absorption, all the parameters are based on the HITRAN database, and an improved detection limit was obtained for interference-free NH3 monitoring, this 2.25 µm band has line strengths several times larger than absorption lines in the 1.53 µm band which was often used by NH3 sensors for emission monitoring and analyzing. The measurement system was developed with a new Herriott cell and a heated gas cell realizing fast absorption measurements of high resolution, and combined with direct absorption and wavelenguh modulation based on tunable diode laser absorption spectroscopy at different temperatures. The lorentzian line shape is dominant at ambient temperature and pressure, and the estimated detectivity is approximately 0.225 x 10(-6) (SNR = 1) for the directed absorption spectroscopy, assuming a noise-equivalent absorbance of 1 x 10(-4). The heated cell experiments with controlled the temperature were performed to validate the sensing strategy. Here the Wavelength Modulation Spectroscopy (WMS) strategy was usually used to measure lower gas concentration for high noise immunity to the non-absorption transmission losses. The great agreement 2f signal with the calibrated concentration is within the uncertainty at different temperatures by using simple digital signal processing such as multiple averages, wavelet analysis and so on. The denoise processing has a great advantage in application and implementation over other noise suppression techniques. The result provided a good basis for trace ammonia escape detection based on tunable diode laser absorption spectroscopy.
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Background: Egl-9 family hypoxia-inducible factor 3 (EGLN3) is involved in the regulation of tumor microenvironment and tumor progression. However, its biological function and clinical significance in various cancers remain unclear. Methods: RNA-seq, immunofluorescence, and single-cell sequencing were used to investigate the expression landscape of EGLN3 in pan-cancer. The TISCH2 and CancerSEA databases were used for single-cell function analysis of EGLN3 in tumors. TIMER2.0 database was used to explain the relationship between EGLN3 expression and immune cell infiltration. In addition, the LinkedOmics database was used to perform KEGG enrichment analysis of EGLN3 in pan-cancer. siRNA was used to silence gene expression. CCK8, transwell migration assay, flow cytometry analysis, RT-PCR, and western blotting were used to explore biological function of EGLN3. Results: The results showed that EGLN3 was highly expressed in a variety of tumors, and was mainly localized to the cytosol. EGLN3 expression is associated with immunoinfiltration of a variety of immune cells, including macrophages in the tumor immune microenvironment and tumor-associated fibroblasts. Functional experiments revealed that EGLN3 knockdown could inhibit cell proliferation, migration, and promote cell apoptosis. In addition, we found that Bax expression was up-regulated and Bcl-2 expression was down-regulated in the si-EGLN3 group. Taken together, as a potential oncogene, EGLN3 is involved in the regulation of tumor malignant process, especially tumor cell apoptosis. Conclusion: We comprehensively investigated the expression pattern, single-cell function, immune infiltration level and regulated signaling pathway of EGLN3 in pan-cancer. We found that EGLN3 is an important hypoxia and immune-related gene that may serve as a potential target for tumor immunotherapy.
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Bacteria, especially drug-resistant strains, can quickly cause wound infections, leading to delayed healing and fatal risk in clinics. With the growing need for alternative antibacterial approaches that rely less on antibiotics or eliminate their use altogether, a novel antibacterial hydrogel named Ovtgel is developed. Ovtgel is formulated by chemically crosslinking thiol-modified ovotransferrin (Ovt), a member of the transferrin family found in egg white, with olefin-modified agarose through thiol-ene click chemistry. Ovt is designed to sequester ferric ions essential for bacterial survival and protect wound tissues from damages caused by the reactive oxygen species (ROS) generated in Fenton reactions. Experimental data have shown that Ovtgel significantly enhances wound healing by inhibiting bacterial growth and shielding tissues from ROS-induced harms. Unlike traditional antibiotics, Ovtgel targets essential trace elements required for bacterial survival in the host environment, preventing the development of drug resistance in pathogenic bacteria. Ovtgel exhibits excellent biocompatibility due to the homology of Ovt to mammalian transferrin. This hydrogel has the potential to serve as an effective antibiotic-free solution for combating bacterial infections.
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OBJECTIVE: To explore the prevalence and risk factors of atherosclerotic renal artery stenosis (ARAS) in patients undergoing coronary angiography. METHODS: A total of 2506 patients with suspected and known coronary heart disease (CAD) at our hospital underwent simultaneous coronary and renal angiography. Renal artery stenosis was defined as at least one of renal artery stenosis ≥ 50% narrowing of luminal diameter. The prevalence of ARAS was summarized from the results of angiography. And single- and multi-variable logistic regression analysis was used to assess the relationship between clinical characteristics and ARAS. RESULTS: Among them, there were 1479 males and 1027 females with a mean age of 62.7 ± 11.4 years. ARAS was detected in 409 patients (16.3%), including 214 (8.5%) with significant stenosis (≥ 75%); Bilateral ARAS was detected in 98 patients (3.9%), including 27 (1.1%) with significant stenosis (≥ 75%). Left and right ARAS were detected in 162 patients (6.5%) and 148 patients (5.9%) respectively, including 84 patients (3.4%) with significant stenosis (≥ 75%) in left ARAS and 72 patients (2.9%) in right ARAS. Univariate analysis indicated that age, females, diabetes, hypertension, stroke, peripheral artery disease, coronary heart disease, renal insufficiency, dyslipidemia and hyperuricemia were the predictor for ARAS (P < 0.05 or 0.01). Multivariate regression analysis demonstrated that age ≥ 65 years (P = 0.025, OR = 1.358), females (P < 0.01, OR = 1.678), hypertension (P < 0.01, OR = 1.650), peripheral artery disease (P < 0.01, OR = 14.678), renal insufficiency (P < 0.01, OR = 1.835), coronary heart disease including 3-vessel (P < 0.01, OR = 1.746) and left main coronary (P < 0.01, OR = 3.416)disease were independent risk factors for ARAS. CONCLUSION: Renal angiography should be routinely performed in female patients aged ≥ 65 years with hypertension, peripheral artery disease, elevated creatinine and coronary heart disease, especially for 3-vessel and left main coronary disease to identify ARAS in time.
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Arteriosclerose/complicações , Obstrução da Artéria Renal/etiologia , Idoso , Arteriosclerose/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Obstrução da Artéria Renal/epidemiologia , Fatores de RiscoRESUMO
AIM: To assess metrics of diffusion tensor imagining (DTI) in evaluating microstructural abnormalities of horizontal extraocular muscles (EOM) in esotropia. METHODS: Six adult concomitant esotropia patients, 5 unilateral abducent paralysis patients and 2 healthy volunteers were enrolled. Conventional magnetic resonance imaging (MRI) and DTI were performed on all subjects using 3T MR scanner. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) of medial and lateral rectus muscles were measured and compared between patients group and control group. RESULTS: Medial rectus MD and RD within the adducted eye of concomitant patients was significantly greater than that in unilateral abducent paralysis patients (0.259×10-2 mm2/s vs 0.207×10-2 mm2/s, P=0.014; 0.182×10-2 mm2/s vs 0.152×10-2 mm2/s, P=0.017). Both strabismus patients showed a significantly decreased MD and AD than that obtained in normal controls for lateral rectus muscles (P<0.05). Medial rectus MD of the adducted eye in concomitant strabismus patients was significantly decreased than that in healthy controls (0.259×10-2 mm2/s vs 0.266×10-2 mm2/s, P=0.010). Lateral rectus AD of the adducted eye in concomitant strabismus patients was significantly decreased as compared with that in healthy controls (0.515×10-2 mm2/s vs 0.593×10-2 mm2/s, P=0.013). No statistically significant differences were present between the adducted and fixating eyes in concomitant strabismus patients. CONCLUSION: DTI represents a feasible technique to assess tissue characteristics of EOM. The effects of eye position changes on DTI parameters are subtle. Decreased MD and RD could be evidence for remodeling of the medial rectus muscle contracture. Lower medial and lateral recuts MD of concomitant esotropia patients indicates a thinner fibrous structure of the EOM. Lower MD and AD should be general character of esotropia.
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Intracellular Methicillin-Resistant Staphylococcus aureus (MRSA) remains a major factor of refractory and recurrent infections, which cannot be well addressed by antibiotic therapy. Here, we design a cellular infectious microenvironment-activatable polymeric nano-system to mediate targeted intracellular drug delivery for macrophage reprogramming and intracellular MRSA eradication. The polymeric nano-system is composed of a ferrocene-decorated polymeric nanovesicle formulated from poly(ferrocenemethyl methacrylate)-block-poly(2-methacryloyloxyethyl phosphorylcholine) (PFMMA-b-PMPC) copolymer with co-encapsulation of clofazimine (CFZ) and interferon-γ (IFN-γ). The cellular-targeting PMPC motifs render specific internalization by macrophages and allow efficient intracellular accumulation. Following the internalization, the ferrocene-derived polymer backbone sequentially undergoes hydrophobic-to-hydrophilic transition, charge reversal and Fe release in response to intracellular hydrogen peroxide over-produced upon infection, eventually triggering endosomal escape and on-site cytosolic drug delivery. The released IFN-γ reverses the immunosuppressive status of infected macrophages by reprogramming anti-inflammatory M2 to pro-inflammatory M1 phenotype. Meanwhile, intracellular Fe2+-mediated Fenton reaction together with antibiotic CFZ contributes to increased intracellular hydroxyl radical (â¢OH) generation. Ultimately, the nano-system achieves robust potency in ablating intracellular MRSA and antibiotic-tolerant persisters by synchronous immune modulation and efficient â¢OH killing, providing an innovative train of thought for intracellular MRSA control.
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Antibacterianos , Macrófagos , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Interferon gama , Macrófagos/imunologia , Metalocenos/uso terapêutico , Staphylococcus aureus Resistente à Meticilina/imunologia , Polímeros/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/imunologia , Nanoestruturas/uso terapêuticoRESUMO
Systematic administration of antibiotics to treat infections often leads to the rapid evolution and spread of multidrug-resistant bacteria. Here, an in situ-formed biotherapeutic gel that controls multidrug-resistant bacterial infections and accelerates wound healing is reported. This biotherapeutic gel is constructed by incorporating stable microbial communities (kombucha) capable of producing antimicrobial substances and organic acids into thermosensitive Pluronic F127 (polyethylene-polypropylene glycol) solutions. Furthermore, it is found that the stable microbial communities-based biotherapeutic gel possesses a broad antimicrobial spectrum and strong antibacterial effects in diverse pathogenic bacteria-derived xenograft infection models, as well as in patient-derived multidrug-resistant bacterial xenograft infection models. The biotherapeutic gel system considerably outperforms the commercial broad-spectrum antibacterial gel (0.1% polyaminopropyl biguanide) in pathogen removal and infected wound healing. Collectively, this biotherapeutic strategy of exploiting stable symbiotic consortiums to repel pathogens provides a paradigm for developing efficient antibacterial biomaterials and overcomes the failure of antibiotics to treat multidrug-resistant bacterial infections.
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Anti-Infecciosos , Infecções Bacterianas , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bactérias , Poloxaleno/farmacologia , Infecções Bacterianas/tratamento farmacológicoRESUMO
Strabismus and amblyopia are common ophthalmologic developmental diseases caused by abnormal visual experiences. However, the underlying pathogenesis and visual defects are still not fully understood. Most studies have used experimental interference to establish disease-associated animal models, while ignoring the natural pathophysiological mechanisms. This study was designed to investigate whether natural strabismus and amblyopia are associated with abnormal neurological defects. We screened one natural strabismic monkey ( Macaca fascicularis) and one natural amblyopic monkey from hundreds of monkeys, and retrospectively analyzed one human strabismus case. Neuroimaging, behavioral, neurophysiological, neurostructural, and genovariation features were systematically evaluated using magnetic resonance imaging (MRI), behavioral tasks, flash visual evoked potentials (FVEP), electroretinogram (ERG), optical coherence tomography (OCT), and whole-genome sequencing (WGS), respectively. Results showed that the strabismic patient and natural strabismic and amblyopic monkeys exhibited similar abnormal asymmetries in brain structure, i.e., ipsilateral impaired right hemisphere. Visual behavior, visual function, retinal structure, and fundus of the monkeys were impaired. Aberrant asymmetry in binocular visual function and structure between the strabismic and amblyopic monkeys was closely related, with greater impairment of the left visual pathway. Several similar known mutant genes for strabismus and amblyopia were also identified. In conclusion, natural strabismus and amblyopia are accompanied by abnormal asymmetries of the visual system, especially visual neurophysiological and neurostructural defects. Our results suggest that future therapeutic and mechanistic studies should consider defects and asymmetries throughout the entire visual system.
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Potenciais Evocados Visuais , Vias Visuais , Animais , Humanos , Estudos Retrospectivos , HaplorrinosRESUMO
The distribution of polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDD/Fs), in brief dioxins, has seldom been addressed systematically in fly ash from municipal solid waste incinerators (MSWIs). This study shows the amount and fingerprint of PCDD/Fs in fly ash from four different Chinese MSWIs, that is, three mechanical grate units and one circulating fluidized bed unit. In these fly ash samples, dioxins-related parameters (international toxic equivalent quantity, total amount of PCDD/Fs, individual isomer classes, and 17 toxic 2,3,7,8-substituted congeners) all tend to increase with decreasing particle size for mechanical grate incinerators, yet only for the finest fraction for fluidized bed units. Moreover, the fluidized bed incinerator seems superior to grate incineration in controlling dioxins, yet a comparison is hampered by internal differences in the sample, for example, the fluidized bed fly ash has much lower carbon and chlorine contents. In addition, the presence of sulfur from mixing coal as supplemental fuel to the MSW may poison the catalytic steps in dioxins formation and thus suppress the formation of dioxins. With more residual carbon and chlorine in the fly ash, it is easier to form dioxins during cooling. Nevertheless, there is no apparent relation between Fe, Cu, and Zn contents and that of dioxins in fly ash.
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Poluentes Atmosféricos/química , Cinza de Carvão/química , Dioxinas/química , Incineração , China , Tamanho da PartículaRESUMO
The objectives of this study were to determine the environmental impacts of polychlorinated dibenzo-p-dioxin and polychlorinated dibenzofuran (PCDD/Fs) emitted from two typical municipal solid-waste incinerators (MSWIs), named M and L, in China. The main differences between the two MSWIs relate to incineration technologies, treatment capacities, emission standards and meteorological conditions. The distribution of PCDD/Fs in the surrounding ambient air and soils of the MWSIs were monitored and compared. In addition, air dispersion models and health risk assessments were combined to determine the behaviour and transport of PCDD/Fs. The results indicated that higher PCDD/F emission levels resulted in higher concentrations in the surrounding environment. The average PCDD/F levels emitted from the M MSWI was about seven times higher than those emitted from the L MSWI and about 10 times and 2 times higher in air and soils, respectively. The simulation results were similar to the trend of the monitored results. Both the observed and the simulation results suggested that the atmospheric pollution by PCDD/F surrounding the M MSWI was relatively serious; the environmental impact of the L MSWI was not significant.
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Poluentes Atmosféricos/toxicidade , Benzofuranos/toxicidade , Exposição Ambiental , Incineração , Dibenzodioxinas Policloradas/análogos & derivados , Eliminação de Resíduos/métodos , Medição de Risco , Poluentes Atmosféricos/análise , Benzofuranos/análise , China , Dibenzofuranos Policlorados , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Dibenzodioxinas Policloradas/análise , Dibenzodioxinas Policloradas/toxicidadeRESUMO
The experimental method by using the tunable diode laser absorption spectroscopy combined with the model and algo- rithm was studied to reconstruct the two-dimensional distribution of gas concentration The feasibility of the reconstruction program was verified by numerical simulation A diagnostic system consisting of 24 lasers was built for the measurement of H2O in the methane/air premixed flame. The two-dimensional distribution of H2O concentration in the flame was reconstructed, showing that the reconstruction results reflect the real two-dimensional distribution of H2O concentration in the flame. This diagnostic scheme provides a promising solution for combustion control.