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1.
Brief Bioinform ; 2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34624074

RESUMO

The biological functions of DNA and RNA generally depend on their interactions with other molecules, such as small ligands, proteins and nucleic acids. However, our knowledge of the nucleic acid binding sites for different interaction partners is very limited, and identification of these critical binding regions is not a trivial work. Herein, we performed a comprehensive comparison between binding and nonbinding sites and among different categories of binding sites in these two nucleic acid classes. From the structural perspective, RNA may interact with ligands through forming binding pockets and contact proteins and nucleic acids using protruding surfaces, while DNA may adopt regions closer to the middle of the chain to make contacts with other molecules. Based on structural information, we established a feature-based ensemble learning classifier to identify the binding sites by fully using the interplay among different machine learning algorithms, feature spaces and sample spaces. Meanwhile, we designed a template-based classifier by exploiting structural conservation. The complementarity between the two classifiers motivated us to build an integrative framework for improving prediction performance. Moreover, we utilized a post-processing procedure based on the random walk algorithm to further correct the integrative predictions. Our unified prediction framework yielded promising results for different binding sites and outperformed existing methods.

2.
Nat Commun ; 12(1): 5770, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34599160

RESUMO

Metal/oxide interface is of fundamental significance to heterogeneous catalysis because the seemingly "inert" oxide support can modulate the morphology, atomic and electronic structures of the metal catalyst through the interface. The interfacial effects are well studied over a bulk oxide support but remain elusive for nanometer-sized systems like clusters, arising from the challenges associated with chemical synthesis and structural elucidation of such hybrid clusters. We hereby demonstrate the essential catalytic roles of a nanometer metal/oxide interface constructed by a hybrid Pd/Bi2O3 cluster ensemble, which is fabricated by a facile stepwise photochemical method. The Pd/Bi2O3 cluster, of which the hybrid structure is elucidated by combined electron microscopy and microanalysis, features a small Pd-Pd coordination number and more importantly a Pd-Bi spatial correlation ascribed to the heterografting between Pd and Bi terminated Bi2O3 clusters. The intra-cluster electron transfer towards Pd across the as-formed nanometer metal/oxide interface significantly weakens the ethylene adsorption without compromising the hydrogen activation. As a result, a 91% selectivity of ethylene and 90% conversion of acetylene can be achieved in a front-end hydrogenation process with a temperature as low as 44 °C.

3.
Proc Natl Acad Sci U S A ; 118(43)2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34663729

RESUMO

The CO electrooxidation is long considered invincible in the proton exchange membrane fuel cell (PEMFC), where even a trace level of CO in H2 seriously poisons the anode catalysts and leads to huge performance decay. Here, we describe a class of atomically dispersed IrRu-N-C anode catalysts capable of oxidizing CO, H2, or a combination of the two. With a small amount of metal (24 µgmetal⋅cm-2) used in the anode, the H2 fuel cell performs its peak power density at 1.43 W⋅cm-2 When operating with pure CO, this catalyst exhibits its maximum current density at 800 mA⋅cm-2, while the Pt/C-based cell ceases to work. We attribute this exceptional catalytic behavior to the interplay between Ir and Ru single-atom centers, where the two sites act in synergy to favorably decompose H2O and to further facilitate CO activation. These findings open up an avenue to conquer the formidable poisoning issue of PEMFCs.

4.
Artigo em Inglês | MEDLINE | ID: mdl-34648439

RESUMO

Therapeutic ultrasound and microbubble technologies seek to drive systemically administered microbubbles into oscillations that safely manipulate tissue or release drugs. Such procedures often detect the unique acoustic emissions from microbubbles with the intention of using this feedback to control the microbubble activity. However, most sensor systems reported introduce distortions to the acoustic signal. Acoustic shockwaves, a key emission from microbubbles, are largely absent in reported recording, possibly due to the sensors being too large or too narrowband, or having strong phase distortions. Here, we built a sensor array that countered such limitations with small, broadband sensors and a low phase distorting material. We built 8 needle hydrophones with polyvinylidene fluoride (PVDF, diameter: 2 mm) then fit them into a 3D-printed scaffold in a two-layered, staggered arrangement. Using this array, we monitored microbubbles exposed to therapeutically-relevant ultrasound pulses (center frequency: 0.5 MHz, peak-rarefactional pressure: 130-597 kPa, pulse length: 4 cycles). Our tests revealed that the hydrophones were broadband with the best having a sensitivity of -224.8± 3.2 dB re 1 V/µPa from 1 to 15 MHz. The array was able to capture shockwaves generated by microbubbles. The signal-to-noise (SNR) ratio of the array was approximately 2 times higher than individual hydrophones. Also, the array could localize microbubbles (-3dB lateral resolution: 2.37 mm) and determine the cavitation threshold (between 161 kPa and 254 kPa). Thus, the array accurately monitored and localized microbubble activities, and may be an important technological step towards better feedback control methods and safer and more effective treatments.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34687123

RESUMO

Copper-based material is an efficient electrocatalyst for CO2 conversion to C2+ products, most of which will reconstruct to in-situ regenerate active species. It is a challenge to precisely design precatalyst to obtain active sites for CO2 reduction reaction (CO2RR). Herein, we develop a local sulfur doping strategy over the Cu-based metal-organic frameworks precatalyst that disperses stable Cu-S motif in the framework of HKUST-1 (S-HKUST-1). The precatalyst exhibits a high ethylene selectivity in H-type cell with maximum faradaic efficiency (FE) of 60.0%, and delivers a current density of 400 mA cm-2 with ethylene FE to 57.2% in a flow cell. Operando X-ray absorption results demonstrate that Cuδ+ species stabilized by Cu-S motif exist in S-HKUST-1 during CO2RR. Density functional theory calculations indicate the partially oxidized Cuδ+ at Cu/CuxSy interface is favorable for *CO intermediate coupling due to the modest distance of coupling sites and optimized adsorption energy.

6.
ACS Appl Mater Interfaces ; 13(39): 47252-47261, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34546698

RESUMO

Understanding the dynamic process of interfacial charge transfer prior to chemisorption is crucial to the development of electrocatalysis. Recently, interfacial water has been highlighted in transferring protons through the electrode/electrolyte interface; however, the identification of the related structural configurations and their influences on the catalytic mechanism is largely complicated by the amorphous and mutable structure of the electrical double layer (EDL). To this end, sub-nanometric Pt electrocatalysts, potentially offering intriguing activity and featuring fully exposed atoms, are studied to uncover the elusive electrode/electrolyte interface via operando X-ray absorption spectroscopy during the hydrogen evolution reaction (HER). Our results show that the metallic Pt clusters derived from the reduction of sub-nanometric Pt clusters (SNM-Pt) exhibit excellent HER activity, with an only 18 mV overpotential at 10 mA/cm2 and one-magnitude-higher mass activity than commercial Pt/C. More importantly, a unique Pt-interfacial water configuration with a Pt (from Pt clusters)-O (from water) radial distance of approximately 2.5 Å is experimentally identified as the structural foundation for the interfacial proton transfer. Toward high overpotentials, the interfacial water that structurally evolves from "O-close" to "O-far" accelerates the proton transfer and is responsible for the improved reaction rate by increasing the hydrogen coverage.

7.
ACS Appl Mater Interfaces ; 13(38): 45269-45278, 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34520159

RESUMO

Rationally constructing single-atom enzymes (SAEs) with superior activity, robust stability, and good biocompatibility is crucial for tumor therapy but still remains a substantial challenge. In this work, we adopt biocompatible carbon dots as the carrier material to load Ru single atoms, achieving Ru SAEs with superior multiple enzyme-like activity and stability. Ru SAEs behave as oxidase, peroxidase, and glutathione oxidase mimics to synchronously catalyze the generation of reactive oxygen species (ROS) and the depletion of glutathione, thus amplifying the ROS damage and finally causing the death of cancer cells. Notably, Ru SAEs exhibit excellent peroxidase-like activity with a specific activity of 7.5 U/mg, which surpasses most of the reported SAEs and is 20 times higher than that of Ru/C. Theoretical results reveal that the electrons of the Ru 4d orbital in Ru SAEs are transferred to O atoms in H2O2 and then efficiently activate H2O2 to produce •OH. Our work may provide some inspiration for the design of SAEs for cancer therapy.

8.
Pest Manag Sci ; 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34523221

RESUMO

BACKGROUND: The use of chemical insecticides to control Bemisia tabaci Gennadius (Hemiptera: Aleyrodidae) is widespread, although it might exert a sublethal effect on its dominant parasitoid, Encarsia formosa Gahan (Hymenoptera: Aphelinidae). To investigate the sublethal effect of spirotetramat on E. formosa, we observed the ability of E. formosa to locate and handle the host, oviposit and preen after exposure to sublethal concentrations of spirotetramat. RESULTS: After exposure to spirotetramat at LC50 , the response time of E. formosa to the volatile reached 223.40 s and was significantly prolonged. Only 56.44% of the wasps were attracted by the volatile and the insect crawled the slowest among all of the treatments. The averages of oviposition posture adopted and host handled by each E. formosa in 1 h decreased significantly to 1.79 and 1.27, respectively. At the sublethal concentration of LC10 , 94.59% of the wasps were attracted by the volatile and the insect crawled the fastest. The average of host handled by each E. formosa was 3.92, and the frequency of drumming while walking and drumming the host was 12.34 times per second and 12.30 times per second, respectively, demonstrating a significant acceleration in these abilities. CONCLUSION: These findings demonstrate that spirotetramat induced hormesis in E. formosa on exposure to its LC10 concentration and accelerated its host locating, host handling and frequency of antennae drumming. These findings could assist in balancing the chemical and biological control of B. tabaci and enhancing the efficacy of E. formosa as a biocontrol agent.

9.
Front Cell Dev Biol ; 9: 724860, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34568334

RESUMO

Background: Cancer stem cells (CSCs), which are characterized by self-renewal and plasticity, are highly correlated with tumor metastasis and drug resistance. To fully understand the role of CSCs in colorectal cancer (CRC), we evaluated the stemness traits and prognostic value of stemness-related genes in CRC. Methods: In this study, the data from 616 CRC patients from The Cancer Genome Atlas (TCGA) were assessed and subtyped based on the mRNA expression-based stemness index (mRNAsi). The correlations of cancer stemness with the immune microenvironment, tumor mutational burden (TMB), and N6-methyladenosine (m6A) RNA methylation regulators were analyzed. Weighted gene co-expression network analysis (WGCNA) was performed to identify the crucial stemness-related genes and modules. Furthermore, a prognostic expression signature was constructed using the Lasso-penalized Cox regression analysis. The signature was validated via multiplex immunofluorescence staining of tissue samples in an independent cohort of 48 CRC patients. Results: This study suggests that high-mRNAsi scores are associated with poor overall survival in stage IV CRC patients. Moreover, the levels of TMB and m6A RNA methylation regulators were positively correlated with mRNAsi scores, and low-mRNAsi scores were characterized by increased immune activity in CRC. The analysis identified 34 key genes as candidate prognosis biomarkers. Finally, a three-gene prognostic signature (PARPBP, KNSTRN, and KIF2C) was explored together with specific clinical features to construct a nomogram, which was successfully validated in an external cohort. Conclusion: There is a unique correlation between CSCs and the prognosis of CRC patients, and the novel biomarkers related to cell stemness could accurately predict the clinical outcomes of these patients.

11.
Stem Cells Dev ; 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34514861

RESUMO

The aim of this study was to elucidate the mechanism of action of the insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) on the phenotype of the liver cancer stem cells (LCSCs). To gain insight into the mechanism of action of the IGF2BP1 on LCSCs, the IGF2BP1 shRNA sequences were transfected into HCC cells. The LCSC phenotypes were measured by stemness gene expressions, spheroid formations, percentages of the CD133+ cells, colony formations, and tumorigeneses in vivo. Next, we screened for possible molecular mechanisms from the TCGA database, and a methylated RNA immunoprecipitation-qPCR (MeRIP-qPCR) was used to adjust the binding of the IGF2BP1 to the target gene, alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase (MGAT5). The MeRIP-qPCR was used to detect the binding of the IGF2BP1 and MGAT5 via the m6A modification. Furthermore, we adjusted the attenuation of the mRNA of the MGAT5 using quantitative real-time PCR (qRT-PCR). The IGF2BP1 was upregulated in the LCSCs. Furthermore, the IGF2BP1 promoted self-renewal and chemoresistance in human LCSCs and tumorigenesis in mice and it enhanced the expression of stemness genes in the LCSCs compared with the HCC cells. Further exploration indicated that the IGF2BP1 binds directly to the MGAT5 and inhibits its mRNA attenuation, suggesting that the IGF2BP1 impacts MGAT5 mRNA stability via the m6A modification. Thus, it can be concluded that the IGF2BP1 facilitated the LCSC phenotypes by promoting the MGAT5 mRNA stability through the upregulation of the m6A modification of the MGAT5 mRNA.

12.
J Med Genet ; 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34544842

RESUMO

BACKGROUND: A large number of new causative and risk genes for amyotrophic lateral sclerosis (ALS) have been identified mostly in patients of European ancestry. In contrast, we know relatively little regarding the genetics of ALS in other ethnic populations. This study aims to provide a comprehensive analysis of the genetics of ALS in an unprecedented large cohort of Chinese mainland population and correlate with the clinical features of rare variants carriers. METHODS: A total of 1587 patients, including 64 familial ALS (FALS) and 1523 sporadic ALS (SALS), and 1866 in-house controls were analysed by whole-exome sequencing and/or testing for G4C2 repeats in C9orf72. Forty-one ALS-associated genes were analysed. FINDINGS: 155 patients, including 26 (40.6%) FALS and 129 (8.5%) SALS, carrying rare pathogenic/likely pathogenic (P/LP) variants of ALS causative genes were identified. SOD1 was the most common mutated gene, followed by C9orf72, FUS, NEK1, TARDBP and TBK1. By burden analysis, rare variants in SOD1, FUS and TARDBP contributed to the collective risk for ALS (p<2.5e-6) at the gene level, but at the allelic level TARDBP p.Gly294Val and FUS p.Arg521Cys and p.Arg521His were the most important single variants causing ALS. Clinically, P/LP variants in TARDBP and C9orf72 were associated with poor prognosis, in FUS linked with younger age of onset, and C9orf72 repeats tended to affect cognition. CONCLUSIONS: Our data provide essential information for understanding the genetic and clinical features of ALS in China and for optimal design of genetic testing and evaluation of disease prognosis.

13.
Int J Biol Macromol ; 190: 845-852, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34520781

RESUMO

The xyloglucanase gene (RmXEG12A) from Rhizomucor miehei CAU432 was successfully expressed in Pichia pastoris. The highest xyloglucanase activity of 25,700 U mL-1 was secreted using high cell density fermentation. RmXEG12A was optimally active at pH 7.0 and 65 °C, respectively. The xyloglucanase exhibited the highest specific activity towards xyloglucan (7915.5 U mg-1). RmXEG12A was subjected to hydrolyze tamarind powder to produce xyloglucan oligosaccharides with the degree of polymerization (DP) 7-9. The hydrolysis ratio of xyloglucan in tamarind powder was 89.8%. Moreover, xyloglucan oligosaccharides (2.0%, w/w) improved the water holding capacity (WHC) of yoghurt by 1.1-fold and promoted the growth of Lactobacillus bulgaricus and Streptococcus thermophiles by 2.3 and 1.6-fold, respectively. Therefore, a suitable xyloglucanase for tamarind powder hydrolysis was expressed in P. pastoris at high level and xyloglucan oligosaccharides improved the quality of yoghurt.

14.
Aging (Albany NY) ; 13(17): 21571-21586, 2021 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-34517345

RESUMO

Early metastasis of pancreatic cancer (PC) leads to high mortality, and the underlying mechanism of metastasis remains unclear. Tumor necrosis factor superfamily member 9 (TNFSF9) is associated with poor prognosis in PC. Here, we investigated the effect of TNFSF9 on PC proliferation and apoptosis, and focused on the effect of TNFSF9 on PC metastasis and its potential mechanism. We found that TNFSF9 promotes PC metastasis in vivo and in vitro, and may be partially dependent on the Wnt/Snail signaling pathway. In addition, TNFSF9 also regulates the release of cytokines IL-10 and transforming growth factor-ß (TGF-ß) in pancreatic cancer cells through Wnt signaling to induce the M2 polarization of macrophages and promote the migration of PC cells. Overall, our study found that TNFSF9 may directly promote PC metastasis or indirectly promote PC metastasis through macrophage M2 polarization. Our study provides a new costimulatory target for the treatment of PC.

15.
Perioper Med (Lond) ; 10(1): 32, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34538277

RESUMO

BACKGROUND: The influence of sugammadex for reversal of neuromuscular block (NMB) on postoperative pulmonary complications (PPCs), compared with neostigmine, remains to be determined. We performed a meta-analysis of randomized controlled trials (RCTs) to compare the incidence of PPCs between patients who received sugammadex versus neostigmine. METHODS: Relevant studies were obtained by searching the PubMed, Embase, and Cochrane Library databases. A random effects model incorporating the potential heterogeneity was used to pool the results. RESULTS: Fourteen RCTs including 1478 adult patients who underwent surgeries with general anesthesia were included, and of these, 753 received sugammadex and 725 received neostigmine for reversal of NMB. The pooled results showed that sugammadex was associated with a lower risk of overall PPCs compared to neostigmine (odds ratio [OR]: 0.62, 95% confidence interval [CI]: 0.43-0.89, p = 0.01; I2 = 0%). This finding remained consistent after exclusion of two studies with potential overlapping events (OR: 0.58, 95% CI: 0.36-0.96, p = 0.03; I2=9%). Stratified analyses according to the categories of PPCs showed that sugammadex was associated with a significantly lower risk of postoperative respiratory failure (OR: 0.60, 95% CI: 0.38-0.97, p = 0.04; I2 = 0%) but not of postoperative pulmonary infection (OR: 0.79, p = 0.71), atelectasis (OR: 0.78, p = 0.33), or pneumothorax (OR: 0.87, p = 0.79). CONCLUSIONS: Compared with neostigmine, the use of sugammadex for reversal of NMB was associated with a lower risk of PPCs, mainly due to a lower incidence of postoperative respiratory failure with the use of sugammadex.

16.
EClinicalMedicine ; 40: 101111, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34514362

RESUMO

Background: Coronavirus disease 2019 (COVID-19) has evolved into a worldwide pandemic, and has been found to be closely associated with mental and neurological disorders. We aimed to comprehensively quantify the association between mental and neurological disorders, both pre-existing and subsequent, and the risk of susceptibility, severity and mortality of COVID-19. Methods: In this systematic review and meta-analysis, we searched PubMed, Web of Science, Embase, PsycINFO, and Cochrane library databases for studies published from the inception up to January 16, 2021 and updated at July 7, 2021. Observational studies including cohort and case-control, cross-sectional studies and case series that reported risk estimates of the association between mental or neurological disorders and COVID-19 susceptibility, illness severity and mortality were included. Two researchers independently extracted data and conducted the quality assessment. Based on I2 heterogeneity, we used a random effects model to calculate pooled odds ratios (OR) and 95% confidence intervals (95% CI). Subgroup analyses and meta-regression analysis were also performed. This study was registered on PROSPERO (registration number: CRD 42021230832). Finding: A total of 149 studies (227,351,954 participants, 89,235,737 COVID-19 patients) were included in this analysis, in which 27 reported morbidity (132,727,798), 56 reported illness severity (83,097,968) and 115 reported mortality (88,878,662). Overall, mental and neurological disorders were associated with a significant high risk of infection (pre-existing mental: OR 1·67, 95% CI 1·12-2·49; and pre-existing neurological: 2·05, 1·58-2·67), illness severity (mental: pre-existing, 1·40, 1·25-1·57; sequelae, 4·85, 2·53-9·32; neurological: pre-existing, 1·43, 1·09-1·88; sequelae, 2·17, 1·45-3·24), and mortality (mental: pre-existing, 1·47, 1·26-1·72; neurological: pre-existing, 2·08, 1·61-2·69; sequelae, 2·03, 1·66-2·49) from COVID-19. Subgroup analysis revealed that association with illness severity was stronger among younger COVID-19 patients, and those with subsequent mental disorders, living in low- and middle-income regions. Younger patients with mental and neurological disorders were associated with higher mortality than elders. For type-specific mental disorders, susceptibility to contracting COVID-19 was associated with pre-existing mood disorders, anxiety, and attention-deficit hyperactivity disorder (ADHD); illness severity was associated with both pre-existing and subsequent mood disorders as well as sleep disturbance; and mortality was associated with pre-existing schizophrenia. For neurological disorders, susceptibility was associated with pre-existing dementia; both severity and mortality were associated with subsequent delirium and altered mental status; besides, mortality was associated with pre-existing and subsequent dementia and multiple specific neurological diseases. Heterogeneities were substantial across studies in most analysis. Interpretation: The findings show an important role of mental and neurological disorders in the context of COVID-19 and provide clues and directions for identifying and protecting vulnerable populations in the pandemic. Early detection and intervention for neurological and mental disorders are urgently needed to control morbidity and mortality induced by the COVID-19 pandemic. However, there was substantial heterogeneity among the included studies, and the results should be interpreted with caution. More studies are needed to explore long-term mental and neurological sequela, as well as the underlying brain mechanisms for the sake of elucidating the causal pathways for these associations. Funding: This study is supported by grants from the National Key Research and Development Program of China, the National Natural Science Foundation of China, Special Research Fund of PKUHSC for Prevention and Control of COVID-19, and the Fundamental Research Funds for the Central Universities.

17.
J Med Chem ; 64(15): 11330-11353, 2021 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-34342996

RESUMO

Myeloid cell leukemia 1 (Mcl-1) protein is a key negative regulator of apoptosis, and developing Mcl-1 inhibitors has been an attractive strategy for cancer therapy. Herein, we describe the rational design, synthesis, and structure-activity relationship study of 3,5-dimethyl-4-sulfonyl-1H-pyrrole-based compounds as Mcl-1 inhibitors. Stepwise optimizations of hit compound 11 with primary Mcl-1 inhibition (52%@30 µM) led to the discovery of the most potent compound 40 with high affinity (Kd = 0.23 nM) and superior selectivity over other Bcl-2 family proteins (>40,000 folds). Mechanistic studies revealed that 40 could activate the apoptosis signal pathway in an Mcl-1-dependent manner. 40 exhibited favorable physicochemical properties and pharmacokinetic profiles (F% = 41.3%). Furthermore, oral administration of 40 was well tolerated to effectively inhibit tumor growth (T/C = 37.3%) in MV4-11 xenograft models. Collectively, these findings implicate that compound 40 is a promising antitumor agent that deserves further preclinical evaluations.

18.
Front Immunol ; 12: 700224, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34456912

RESUMO

Background: Complex factors are involved in the development and progression of immunoglobulin A nephropathy (IgAN), a common primary glomerulonephritis worldwide. Autoimmunity and inflammation have been considered to be the basic mechanisms; however, the exact pathogenesis remains unclear. As a novel marker of inflammation, the neutrophil-to-lymphocyte ratio (NLR) has been studied in various diseases. Whether the NLR can predict the renal outcome of patients with IgAN remains unclear. We evaluated the relationships between the NLR and renal function, pathologic lesions, renal progression, and prognosis in patients with IgAN. Methods: This retrospective study involved 966 patients with biopsy-proven IgAN. They were divided into two groups based on the cut-off value of the NLR: the high group (NLR ≥ 2.67, n = 384) and the low group (NLR < 2.67, n = 582). The endpoint was end-stage renal disease [estimated glomerular filtration rate (eGFR) of <15 mL/min/1.73 m2 or performance of renal replacement therapy]. A correlation test was conducted to explore the relationship between the NLR and other important parameters (eGFR, serum creatinine, proteinuria, hypertension and renal pathologic lesions). The predictive value was determined by the area under the receiver operating characteristics curve (AUROC). Kaplan-Meier and Cox proportional hazards analyses were performed to evaluate renal progression and prognosis. Results: The NLR had the highest AUROC, which was 0.633 (p < 0.001). The correlation test revealed that the NLR was positively correlated with serum creatinine (r = 0.127, p < 0.001) and 24-hour urine protein (r = 0.18, p < 0.001) and negatively correlated with eGFR (r = 0.14, p < 0.001). Patients with IgAN who had a high NLR were more likely to have hypertension (p = 0.003). Multivariate Cox regression analysis indicated that a high NLR was an independent risk factor for IgAN even after adjustment for important clinical and pathological parameters (p = 0.043, HR = 1.74, 95%CI: 1.02-2.97). Kaplan-Meier analysis showed that a high NLR was significantly associated with the renal prognosis of patients with IgAN (p < 0.001), especially patients with stage 3 to 4 chronic kidney disease (p = 0.028) or 24-hour urine protein of >1 g/day (p < 0.001). Conclusion: An elevated NLR affects the renal progression and prognosis in patients with IgAN and could be a marker for evaluation of renal function and pathologic lesions.

19.
World J Surg Oncol ; 19(1): 253, 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34446046

RESUMO

BACKGROUND: The impact of primary tumour location on the prognosis of patients with peritoneal metastasis (PM) arising from colorectal cancer (CRC) after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is rarely discussed, and the evidence is still limited. METHODS: Patients with PM arising from CRC treated with CRS and HIPEC at the China National Cancer Center and Huanxing Cancer Hospital between June 2017 and June 2019 were systematically reviewed. Clinical characteristics, pathological features, perioperative parameters, and prognostic data were collected and analysed. RESULTS: A total of 70 patients were divided into two groups according to either colonic or rectal origin (18 patients in the rectum group and 52 patients in the colon group). Patients with PM of a colonic origin were more likely to develop grade 3-4 postoperative complications after CRS+HIPEC (38.9% vs 19.2%, P = 0.094), but this difference was not statistically significant. Patients with colon cancer had a longer median overall survival (OS) than patients with rectal cancer (27.0 vs 15.0 months, P = 0.011). In the multivariate analysis, the independent prognostic factors of reduced OS were a rectal origin (HR 2.15, 95% CI 1.15-4.93, P = 0.035) and incomplete cytoreduction (HR 1.99, 95% CI 1.06-4.17, P = 0.047). CONCLUSION: CRS is a complex and potentially life-threatening procedure, and we suggest that the indications for CRS+HIPEC in patients with PM of rectal origin be more restrictive and that clinicians approach these cases with caution.


Assuntos
Neoplasias Colorretais , Hipertermia Induzida , Neoplasias Peritoneais , Neoplasias Colorretais/tratamento farmacológico , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução , Humanos , Quimioterapia Intraperitoneal Hipertérmica , Neoplasias Peritoneais/tratamento farmacológico , Prognóstico , Taxa de Sobrevida
20.
Oxid Med Cell Longev ; 2021: 9949697, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34336124

RESUMO

Escherichia coli (E. coli) is closely associated with the formation of kidney stones. However, the role of E. coli in CaOx stone formation is not well understood. We explored whether E. coli facilitate CaOx stone formation and its mechanism. Stone and urine cultures were reviewed from kidney stone formers. The ability of calcium oxalate monohydrate (COM) aggregation was detected to evaluate the influence of uropathogenic E. coli, then gel electrophoresis and nanoLC-MS/MS to detect the crystal-adhered protein. Flagellin (Flic) and polyphosphate kinase 1 (PPK1) were screened out following detection of their role on crystal aggregation, oxidative injury, and inflammation of HK-2 cell in vitro. By transurethral injection of wild-type, Ppk1 mutant and Flic mutant strains of E. coli and intraperitoneally injected with glyoxylate in C57BL/6J female mice to establish an animal model. We found that E. coli was the most common bacterial species in patients with CaOx stone. It could enhance CaOx crystal aggregation both in vitro and in vivo. Flagellin was identified as the key molecules regulated by PPK1, and both of them could facilitate the crystal aggregation and mediated HK-2 cell oxidative injury and activated the inflammation-related NF-κB/P38 signaling pathway. Wild-type strain of E. coli injection significantly increased CaOx deposition and enhanced oxidative injury and inflammation-related protein expression, and this effect could be reversed by Ppk1 or Flic mutation. In conclusion, E. coli promotes CaOx stone formation via enhancing oxidative injury and inflammation regulated by the PPK1/flagellin, which activated NF-κB/P38 pathways, providing new potential drug targets for the renal CaOx calculus precaution and treatment.

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