Spatial evolution of the proton-coupled Mott transition in correlated oxides for neuromorphic computing.

The proton-electron coupling effect induces rich spectrums of electronic states in correlated oxides, opening tempting opportunities for exploring novel devices with multifunctions. Here, via modest Pt-aided hydrogen spillover at room temperature, amounts of protons are introduced into SmNiO3-based devices. In situ structural characterizations together with first-principles calculation reveal that the local Mott transition is reversibly driven by migration and redistribution of the predoped protons. The accompanying giant resistance change results in excellent memristive behaviors under ultralow electric fields. Hierarchical tree-like memory states, an instinct displayed in bio-synapses, are further realized in the devices by spatially varying the proton concentration with electric pulses, showing great promise in artificial neural networks for solving intricate problems. Our research demonstrates the direct and effective control of proton evolution using extremely low electric field, offering an alternative pathway for modifying the functionalities of correlated oxides and constructing low-power consumption intelligent devices and neural network circuits.

Ammonia stripping by in situ biogas self-circulation to upgrade continuous thermophilic and mesophilic digestion of hydrothermal high-solid sludge.

High-solid anaerobic digestion of hydrothermal sewage sludge has been developed. In order to upgrade the process by focusing on ammonia inhibition, a simply-equipped stripping system without additional alkali or heat supply was introduced by in situ biogas self-circulation. As the determined limit of total ammonia nitrogen at 1500 mg/L and 1000 mg/L for the mesophilic (MAD) and thermophilic anaerobic digestion (TAD) respectively and stripping rate at 5 L/min, continuous MAD and TAD was conducted in parallel. The stripping system successfully polished up the ammonia inhibition, and methanogenic capability of the TAD was promoted to approximately 90.0 % of the potential. Intermittent stripping mode proved usable. More frequent stripping was inevitable for the TAD as compared to the MAD. Hydraulic retention time below 20 d resulted in failure of the stripping mode due to rapid ammonia generation. Overall, this technology was practical in upgrading high-solid sludge digestion by effective ammonia control.

Efficacy and safety of vonoprazan-based dual therapy and esomeprazole-based dual therapy in eradicating primary Helicobacter pylori infection: A propensity score matching analysis.

BACKGROUND: According to the Maastricht VI/Florence consensus report, potassium-competitive acid blockers (P-CAB) may improve Helicobacter pylori eradication treatment. MATERIALS AND METHODS: A total of 213 H. pylori treatment-naive patients aged between 18 and 70 years were treated with two regimens. The two regimens are VDT: 20 mg vonoprazan twice a day and 1 g amoxicillin three times daily and EDT: 20 mg esomeprazole four times a day and 750 mg amoxicillin four times daily. 13 C-urea breath tests were used to evaluate eradication rate 4-6 weeks after treatment. Based on propensity score matching (PSM), this retrospective study analyzed the eradication rates, adverse events (AEs), compliance, and antibiotic resistance rates in VDT and EDT groups. RESULTS: On intention-to-treat (ITT) analysis, the eradication rate in VDT group (89.0%; 95% CI 81.7-96.3) was non-inferior to that in EDT group (87.7%; 95% CI 80.1-95.3; p = 0.796). The corresponding per-protocol (PP) eradication rates were 94.1% (95% CI 88.4-99.8) and 92.8% (95% CI 86.7-98.9; p = 1.000), respectively. There were no significant between-group differences with respect to compliance or incidence of AEs. CONCLUSIONS: The efficacy and safety of 14-day VDT and EDT were comparable. Therefore, 14-day VDT or EDT may be recommended for the first-line treatment of H. pylori infection.

A case report of Trousseau syndrome.

RATIONALE: In 1865, Trousseau first discovered pulmonary embolism caused by multiple venous thrombosis in patients with gastric cancer, and later all clinical manifestations of malignant patients during pathogenesis due to abnormal coagulation and fibrinolysis were referred to collectively as Trousseau syndrome. Trousseau syndrome is not a benign thrombophlebitis, and when diagnosed it requires immediate treatment. The survival rate over 1 year is only 12%. Stroke in cancer patients has distinct characteristics different from conventional stroke and has higher mortality. PATIENT CONCERNS: A 54-year-old female presented to the Department of Otolaryngology with recurrent right nasal bleeding for 4 days. After surgery, the patient experienced 7 different cerebral infarction courses. Finally died of brain herniation. DIAGNOSIS: The specific abnormal laboratory index is the increase of D-dimer, suggesting the hypercoagulation state. The patient developed multiple cerebral infarction, myocardial injury, renal infarction, splenic infarction, and lower extremity arterial thrombosis, and finally was diagnosed Trousseau syndrome. INTERVENTIONS: In the treatment, aspirin and atorvastatin were selected, but it did not work very well. D-dimer were high, we used low molecular weight heparin, and D-dimer decreased significantly. OUTCOMES: Finally the patient died of brain herniation. CONCLUSION: The raise of D-dimer and typical magnetic resonance imaging manifestation which provides a greater basis for diagnosis. The specific abnormal laboratory index is the increase of D-dimer, which provides direction for treatment and helps to evaluate treatment effect.

Eradication rates of Helicobacter pylori in treatment-naive patients following 14-day vonoprazan-amoxicillin dual therapy: A multicenter randomized controlled trial in China.

BACKGROUND: Potassium-competitive acid blockers (P-CAB) are recommended for the treatment of Helicobacter pylori infections, but dual therapy of P-CAB with amoxicillin has been poorly studied. The current study compared the efficacy, adverse reactions, compliance, and effects on gut microbiota of 14-day vonoprazan-amoxicillin (VA) dual therapy with esomeprazole, bismuth potassium citrate, amoxicillin, and metronidazole (EBAM) quadruple therapy in treatment-naive patients with H. pylori. MATERIALS AND METHODS: This was a multicenter, open-label, randomized, and controlled, non-inferiority study. Patients (n = 194) enrolled from six centers were randomly divided into either the VA or EBAM group. H. pylori eradication was determined using 13 C urea breath tests (UBT) 4-6 weeks post-treatment. Fecal samples were collected, and gut microbial populations were analyzed by 16S rDNA and metagenomic sequencing technology. RESULTS: Eradication rates of H. pylori in the VA and EBAM groups were 88.7% and 91.8%, respectively, according to intention-to-treat (ITT) analysis; 95.6% and 96.7% with per-protocol (PP) analysis; and 94.5% and 96.7% with modified ITT (mITT) analysis (all p > 0.05). The incidence of adverse reactions in the VA group was significantly lower compared to the EBAM group, and compliance within both groups was good. There was no difference in α-diversity or microbial composition in the VA and EBAM groups at one-month post-treatment compared to baseline, except for a markedly reduced abundance of Bacteroides in the EBAM group. CONCLUSION: VA therapy achieved excellent eradication rates with low adverse reactions, good compliance, and little impact on gut microbiota. VA therapy should be recommended as a first-line treatment against H. pylori.

The effects of the interaction of genetic predisposition with lifestyle factors on bladder cancer risk.

OBJECTIVES: To investigate the association of polygenic risk score (PRS) and bladder cancer (BC) risk and whether this PRS can be offset by a healthy lifestyle. METHODS: Individuals with BC (n = 563) and non-BC controls (n = 483 957) were identified in the UK Biobank, and adjusted Cox regression models were used. A PRS was constructed based on 34 genetic variants associated with BC development, while a healthy lifestyle score (HLS) was constructed based on three lifestyle factors (i.e., smoking, physical activity, and diet). RESULTS: Overall, a negative interaction was observed between the PRS and the HLS (P = 0.02). A 7% higher and 28% lower BC risk per 1-standard deviation (SD) increment in PRS and HLS were observed, respectively. A simultaneous increment of 1 SD in both HLS and PRS was associated with a 6% lower BC risk. In addition, individuals with a high genetic risk and an unfavourable lifestyle showed an increased BC risk compared to individuals with low genetic risk and a favourable lifestyle (hazard ratio 1.55, 95% confidence interval 1.16-1.91; P for trend <0.001). Furthermore, population-attributable fraction (PAF) analysis showed that 12%-15% of the BC cases might have been prevented if individuals had adhered to a healthy lifestyle. CONCLUSION: This large-scale cohort study shows that a genetic predisposition combined with unhealthy behaviours have a joint negative effect on the risk of developing BC. Behavioural lifestyle changes should be encouraged for people through comprehensive, multifactorial approaches, although high-risk individuals may be selected based on genetic risk.

High Throughput Isolation and Data Independent Acquisition Mass Spectrometry (DIA-MS) of Urinary Extracellular Vesicles to Improve Prostate Cancer Diagnosis.

Proteomic profiling of extracellular vesicles (EVs) represents a promising approach for early detection and therapeutic monitoring of diseases such as cancer. The focus of this study was to apply robust EV isolation and subsequent data-independent acquisition mass spectrometry (DIA-MS) for urinary EV proteomics of prostate cancer and prostate inflammation patients. Urinary EVs were isolated by functionalized magnetic beads through chemical affinity on an automatic station, and EV proteins were analyzed by integrating three library-base analyses (Direct-DIA, GPF-DIA, and Fractionated DDA-base DIA) to improve the coverage and quantitation. We assessed the levels of urinary EV-associated proteins based on 40 samples consisting of 20 cases and 20 controls, where 18 EV proteins were identified to be differentiated in prostate cancer outcome, of which three (i.e., SERPINA3, LRG1, and SCGB3A1) were shown to be consistently upregulated. We also observed 6 out of the 18 (33%) EV proteins that had been developed as drug targets, while some of them showed protein-protein interactions. Moreover, the potential mechanistic pathways of 18 significantly different EV proteins were enriched in metabolic, immune, and inflammatory activities. These results showed consistency in an independent cohort with 20 participants. Using a random forest algorithm for classification assessment, including the identified EV proteins, we found that SERPINA3, LRG1, or SCGB3A1 add predictable value in addition to age, prostate size, body mass index (BMI), and prostate-specific antigen (PSA). In summary, the current study demonstrates a translational workflow to identify EV proteins as molecular markers to improve the clinical diagnosis of prostate cancer.

Hollow CoS2 anchored on hierarchically porous carbon derived from Pien Tze Huang for high-performance supercapacitors.

The development of electrode materials with a high specific capacitance, power density, and long-term stability is essential and remains a challenge for developing supercapacitors. Cobalt sulfides (CoS2) are considered one of the most promising and widely studied electrode materials for supercapacitors. Herein, CoS2 and hierarchical porous carbon derived from Pien Tze Huang waste are assembled into a cobalt sulfide/carbon (CoS2/PZH) matrix composite using a one-step hydrothermal method to resolve the challenges of supercapacitors. The resulting CoS2/PZH composite material exhibits a hierarchical porous structure with hollow CoS2 embedded in a PZH framework. The uniform dispersion of the hierarchical porous structure CoS2/PZH is achieved due to the PZH framework, while the uniform decoration of the porous PZH with the hollow CoS2 prevents the PZH from stacking easily. Moreover, the excellent synergistic effect of the hierarchical porous and hollow structure of CoS2/PZH can shorten the electron/ion diffusion channels, expose additional active sites, and provide stable structures for subsequent reactions. As a result, the CoS2/PZH composite material displays a high initial specific capacity of 447.5 F g-1 at 0.5 A g-1, a high energy density of 22.38 W h kg-1, and long-term cycling stability (a retention rate of 92.3% over 10 000 cycles at 5 A g-1).

Integrative Multi-Omics Analysis for the Determination of Non-Muscle Invasive vs. Muscle Invasive Bladder Cancer: A Pilot Study.

OBJECTIVES: The molecular landscape of non-muscle-invasive (NMIBC) and muscle-invasive (MIBC) bladder cancer based on molecular characteristics is essential but poorly understood. In this pilot study we aimed to identify a multi-omics signature that can distinguish MIBC from NMIBC. Such a signature can assist in finding potential mechanistic biomarkers and druggable targets. METHODS: Patients diagnosed with NMIBC (n = 15) and MIBC (n = 11) were recruited at a tertiary-care hospital in Nanjing from 1 April 2021, and 31 July 2021. Blood, urine and stool samples per participant were collected, in which the serum metabolome, urine metabolome, gut microbiome, and serum extracellular vesicles (EV) proteome were quantified. The differences of the global profiles and individual omics measure between NMIBC vs. MIBC were assessed by permutational multivariate analysis and the Mann-Whitney test, respectively. Logistic regression analysis was used to assess the association of each identified analyte with NMIBC vs. MIBC, and the Spearman correlation was used to investigate the correlations between identified analytes, where both were adjusted for age, sex and smoking status. RESULTS: Among 3168 multi-omics measures that passed the quality control, 159 were identified to be differentiated in NMIBC vs. MIBC. Of these, 46 analytes were associated with bladder cancer progression. In addition, the global profiles showed significantly different urine metabolome (p = 0.029), gut microbiome (p = 0.036), and serum EV (extracellular vesicles) proteome (p = 0.039) but not serum metabolome (p = 0.059). We also observed 17 (35%) analytes that had been developed as drug targets. Multiple interactions were obtained between the identified analytes, whereas for the majority (61%), the number of interactions was at 11-20. Moreover, unconjugated bilirubin (p = 0.009) and white blood cell count (p = 0.006) were also shown to be different in NMIBC and MIBC, and associated with 11 identified omics analytes. CONCLUSIONS: The pilot study has shown promising to monitor the progression of bladder cancer by integrating multi-omics data and deserves further investigations.

Facile fabrication of self-supporting porous CuMoO4@Co3O4 nanosheets as a bifunctional electrocatalyst for efficient overall water splitting.

Research shows that redox complementarity and synergism among the ingredients of heterogeneous catalysts can enhance the performance of the catalyst. In this research, a porous CuMoO4@Co3O4 nanosheet electrocatalyst is prepared, which is uniformly decorated on nickel foam (NF) by hydrothermal reactions and the impregnation method. The CuMoO4@Co3O4 is an efficient bifunctional catalyst with prominent electrocatalytic activity and durability. It requires overpotentials of only 54 and 251 mV to obtain current densities of 10 and 50 mA cm-2 for the cathodic hydrogen evolution reaction (HER) and the anodic oxygen evolution reaction (OER) in 1.0 mol L-1 KOH, corresponding to Tafel slope values of 98.8 and 87.4 mV dec-1, respectively. Furthermore, the CuMoO4@Co3O4 shows excellent stability of 120 h chronopotentiometry at a current density of 100 mA cm-2 for the HER/OER. Notably, an alkaline electrolyzer (with CuMoO4@Co3O4 as the HER and OER electrodes) can deliver a current density of 10 mA cm-2 at a low voltage of 1.51 V. The catalytic activity of CuMoO4@Co3O4 can be attributed to the structure of the porous nanosheets and the synergistic effect between CuMoO4 and Co3O4.

Effect of Agkistrodon halys antivenom in patients bit by green pit viper and the prognostic role of the disease - a retrospective cohort study.

BACKGROUND AND AIMS: In Mainland China and Hong Kong, health authorities utilize Agkistrodon halys antivenom in the treatment of patients who sustained bites from green pit vipers. However, the treatment benefit of Agkistrodon halys antivenom among such patients is still controversial. The purpose of this study is to evaluate the coagulation parameters normalization time of Agkistrodon halys antivenom in patients who sustained green pit viper bites and explore independent risk factors of patient prognosis. METHODS: Data were extracted from the Donghua Hospital Information System. Comparison of the two groups of patients - who used antivenom (GPUA) and who did not use antivenom (GPNUA) were performed using stratified analysis, univariate and multivariate ordered logistic regression models to evaluate the coagulation parameters normalization time. Univariate and multivariate ordered logistic regression models were used to explore independent risk factors of patient prognosis. RESULTS: Between the GPUA and GPNUA groups, there is no significant difference in the coagulation parameters normalization time with the treatment of Agkistrodon halys antivenom. GPNUA consumed more cryoprecipitate and platelets and had a lower cost. The patient's severity of the bite, first coagulation profile, and dosages of fresh frozen plasma, platelet, and red cell suspension was found to be risk factors for the normalization time of coagulation parameters. CONCLUSIONS: The therapeutic effect of Agkistrodon halys antivenom in green pit vipers bite patients is not quite satisfying. In addition, more attention should be paid to the first coagulation profile, blood clotting factors indices, platelet count (PLT), and hemoglobin when treating such patients.

RNA-binding motif protein RBM47 promotes tumorigenesis in nasopharyngeal carcinoma through multiple pathways.

RNA binding motif proteins (RBMs) have been widely implicated in the tumorigenesis of multiple human cancers but scarcely studied in nasopharyngeal carcinoma (NPC). Here, we compare the mRNA levels of 29 RBMs between 87 NPC and 10 control samples. We find that RBM47 is frequently upregulated in NPC specimens, and its high expression is associated with the poor prognosis of patients with NPC. Biological experiments show that RBM47 plays an oncogenic role in NPC cells. Mechanically, RBM47 binds to the promoter and regulates the transcription of BCAT1, and its overexpression partially rescues the inhibitory effects of RBM47-knockdown on NPC cells. Moreover, transcriptome analysis reveals that RBM47 regulates alternative splicing of pre-mRNA, including those cancer-related, to a large extent in NPC cells. Furthermore, RBM47 binds to hnRNPM and cooperatively regulates multiple splicing events in NPC cells. In addition, we find that knockdown of hnRNPM inhibits proliferation and migration of NPC cells. Our study, taken together, shows that RBM47 promotes the progression of NPC through multiple pathways, acting as a transcriptional factor and a modulator of alternative splicing in cooperation with hnRNPM. Our study also highlights that RBM47 and hnRNPM could be prognostic factors and potential therapeutic targets for NPC.

RBFOX2/GOLIM4 Splicing Axis Activates Vesicular Transport Pathway to Promote Nasopharyngeal Carcinogenesis.

20-30% of patients with nasopharyngeal carcinoma (NPC) develop distant metastasis or recurrence leading to poor survival, of which the underlying key molecular events have yet to be addressed. Here alternative splicing events in 85 NPC samples are profiled using transcriptome analysis and it is revealed that the long isoform of GOLIM4 (-L) with exon-7 is highly expressed in NPC and associated with poor prognosis. Lines of evidence demonstrate the pro-tumorigenic function of GOLIM4-L in NPC cells. It is further revealed that RBFOX2 binds to a GGAA motif in exon-7 and promotes its inclusion forming GOLIM4-L. RBFOX2 knockdown suppresses the tumorigenesis of NPC cells, phenocopying GOLIM4-L knockdown, which is significantly rescued by GOLIM4-L overexpression. High expression of RBFOX2 is correlated with the exon-7 inclusion of GOLIM4 in NPC biopsies and associated with worse prognosis. It is observed that RBFOX2 and GOLIM4 can influence vesicle-mediated transport through maintaining the organization of Golgi apparatus. Finally, it is revealed that RAB26 interacts with GOLIM4 and mediates its tumorigenic potentials in NPC cells. Taken together, the findings provide insights into how alternative splicing contributes to NPC development, by highlighting a functional link between GOLIM4-L and its splicing regulator RBFOX2 activating vesicle-mediated transport involving RAB26.

Optimization of hydrothermal pretreatment conditions for mesophilic and thermophilic anaerobic digestion of high-solid sludge.

Hydrothermal pretreatment (HTP) conditions were optimized for continuous mesophilic (MAD) and thermophilic (TAD) anaerobic digestion of high-solid sludge (10-11% total solids). COD solubilization increased with prolonged HTP durations, and became not significant after 210 min. According to the methane production rate and energy consumption, the optimal HTP temperature was determined at 160 °C. Regarding continuous operation without HTP, TAD achieved higher methane yield and volatile solids (VS) reduction, at 0.12 L/g VSadded and 23.9%, respectively. After HTP, methane yield and VS reduction in MAD and TAD were increased by 400% and 191% (MAD), 67% and 72% (TAD), respectively. TAD was limited due to the inhibition from about 2800 mg/L of NH4+-N concentration. The methanogenic activity of MAD was enhanced, whereas TAD displayed a reduced value owing to ammonia inhibition. Ultimately, MAD with HTP and TAD without HTP achieved the higher energy balance, 5.25 and 3.27 kJ/g VS, respectively.

Investigation of Allergic Sensitization Pattern in 4,203 Children in Northern China.

OBJECTIVE: The objective of this study is to investigate the allergen sensitization pattern among 4,203 children in the Shanxi region of China and to provide guidance for diagnosis and prevention of allergic diseases. METHODS: A retrospective analysis was conducted on the allergen-specific immunoglobulin E (sIgE) results of 4,203 children aged 0-12 years from January to December in 2019. SIgE antibodies to 19 allergens in the serum sample were detected by enzyme ALLERGO-SORBENT testing. RESULTS: In total, 49.70% (2,089/4,203) of children with allergic diseases were positive for sIgE, and the top 5 allergens were egg white 18.63% (783/4,203), artemisia 14.47% (608/4,203), milk 13.04% (548/4,203), ragweed 8.66% (364/4,203), and poplar/willow/elm 8.52% (358/4,203). Significant differences in the positive rate of food allergens and aeroallergens in different ages were found (p < 0.05). 50.98% (1,065/2,089) patients were sensitive to 2 or more allergens. The high sensitization rate in the >3-year group was significantly higher than the ≤3-year group (p < 0.05). CONCLUSION: Egg white and artemisia are the most common allergens in children in northern China. This study provides allergic sensitization pattern of children and clinical epidemiological data in the region.

Microbial cell-free DNA in plasma of patients with sepsis: a potential diagnostic methodology.

Sepsis is a life-threatening clinical condition demanding accurate and rapid diagnosis of the culprit pathogen, thereby to improve prognosis. Pathogen determination through blood culture is the gold standard for diagnosis but has limitations due to low sensitivity. Recently, circulating DNAs derived from pathogenic organisms were found in the plasma of patients with sepsis and were further proved to be more sensitive biomarkers for the diagnosis of the pathogen origin in sepsis. However, the fundamental molecular characteristics of circulating DNA in patients with sepsis remain unclear. Here, we used specific PCR and Sanger sequencing to verify the microbiology culture results via the corresponding plasma circulating DNA. We analyzed the composition and molecular characteristics of circulating DNA in septic patients using next-generation sequencing technology. We showed the presence of pathogen-derived circulating DNA in the plasma of patients with sepsis. The sizes of circulating DNA fragments derived from pathogenic bacteria showed a skewed unimodal distribution, while those derived from host cells showed a normal unimodal distribution. Lengths of fragments at peak concentration for both origins ranged from 150 bp to 200 bp, and reads mapping to pathogenic bacteria genome distributed uniformly on the reference. Our findings have improved our understanding of microbial circulating DNA in patients with sepsis as a potential methodology for the accurate diagnosis of sepsis, especially in light of an urgent need for such a diagnosis associated with the COVID-19 infection.

Node Deployment of Marine Monitoring Networks: A Multiobjective Optimization Scheme.

The increasing demands for real-time marine monitoring call for the wide deployment of Marine Monitoring Networks (MMNs). The low-rate underwater communications over a long distance, long propagation delay of underwater acoustic channel, and high deployment costs of marine sensors in a large-scale three-dimensional space bring great challenges in the network deployment and management of MMN. In this paper, we first propose a multitier, hierarchical network architecture of MMN with the support of edge computing (HMMN-EC) to enable efficient monitoring services in a harsh marine environment, taking into consideration the salient features of marine communications. Specifically, HMMN-EC is composed of three subnetworks, i.e., underwater acoustic subnetwork, the sea-surface wireless subnetwork, and the air wireless subnetwork, with a diversity of network nodes with different capabilities. We then jointly investigate the deployment diverse network nodes with various constraints in different subnetworks of HMMN-EC. To this end, we formulate a Multiobjective Optimization (MO) problem to minimize the network deployment cost while achieving the maximal network lifetime, subject to the limited energy of different marine nodes and the complex deployment environment. To solve the formulated problem, we present an Ant-Colony-based Efficient Topology Optimization (AC-ETO) algorithm to find the optimal locations of nodes in different subnetworks of MMN in a large-scale deployment. The time complexity of the proposed algorithm is also analyzed. Finally, extensive simulations are carried out to validate the superior performance of the proposed algorithm compared with some existing solutions.

Germline Polymorphisms and Length of Survival of Nasopharyngeal Carcinoma: An Exome-Wide Association Study in Multiple Cohorts.

Germline polymorphisms are linked with differential survival outcomes in cancers but are not well studied in nasopharyngeal carcinoma (NPC). Here, a two-phase association study is conducted to discover germline polymorphisms that are associated with the prognosis of NPC. The discovery phase includes two consecutive hospital cohorts of patients with NPC from Southern China. Exome-wide genotypes at 246 173 single nucleotide polymorphisms (SNPs) are determined, followed by survival analysis for each SNP under Cox proportional hazard regression model. Candidate SNP is replicated in another two independent cohorts from Southern China and Singapore. Meta-analysis of all samples (n = 5553) confirms that the presence of rs1131636-T, located in the 3'-UTR of RPA1, confers an inferior overall survival (HR = 1.33, 95% CI = 1.20-1.47, P = 6.31 × 10-8). Bioinformatics and biological assays show that rs1131636 has regulatory effects on upstream RPA1. Functional studies further demonstrate that RPA1 promotes the growth, invasion, migration, and radioresistance of NPC cells. Additionally, miR-1253 is identified as a suppressor for RPA1 expression, likely through regulation of its binding affinity to rs1131636 locus. Collectively, these findings provide a promising biomarker aiding in stratifying patients with poor survival, as well as a potential drug target for NPC.

Association of MCP-1 promoter polymorphism with susceptibility to nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is prevalent among populations from southern China and is influenced by both genetic and environmental risk factors. The monocyte chemoattractant protein-1 (MCP-1), a member of cysteine-cysteine chemokine family, plays critical roles in cancers. A polymorphism within the MCP-1 promoter, rs1024611, has been shown to be significantly associated with the risk of several cancers. Our purpose was to assess the role of rs1024611 in NPC susceptibility. By polymerase chain reaction-restriction fragment length polymorphism method, we genotyped rs1024611 in 593 patients with NPC (cases) and 480 cancer-free subjects (controls) among Guangxi population from southern China. We observed that the G allele of rs1024611 was significantly associated with the increased risk of NPC in an additive model and dominant model, respectively (P = 0.018 and 0.010, odds ratio = 1.25 and 1.41, respectively). No appreciable variation of the effects was found across the subgroups stratified by age, sex, nationality, smoking and drinking status, and smoking level. In addition, significantly higher messenger RNA (mRNA) expression level of MCP-1 was observed in NPC tissues than that in normal nasopharyngeal tissues, and the G allele of rs1024611 was significantly associated with elevated mRNA expression level of MCP-1 in Epstein-Barr virus-transformed lymphocytes. In conclusion, our findings suggested that rs1024611 at the MCP-1 promoter may be a risk factor for NPC. Further studies with larger sample size are necessary to confirm these findings.