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Abstract Background The male predominance in the incidence of nasopharyngeal carcinoma (NPC) suggests the contribution of the X chromosome to the susceptibility of NPC. However, no X-linked susceptibility loci have been examined by genome-wide association studies (GWASs) for NPC by far. Methods To understand the contribution of the X chromosome in NPC susceptibility, we conducted an X chromosome-wide association analysis on 1615 NPC patients and 1025 healthy controls of Guangdong Chinese, followed by two validation analyses in Taiwan Chinese (n = 562) and Malaysian Chinese (n = 716). Results Firstly, the proportion of variance of X-linked loci over phenotypic variance was estimated in the discovery samples, which revealed that the phenotypic variance explained by X chromosome polymorphisms was estimated to be 12.63% (non-dosage compensation model) in males, as compared with 0.0001% in females. This suggested that the contribution of X chromosome to the genetic variance of NPC should not be neglected. Secondly, association analysis revealed that rs5927056 in DMD gene achieved X chromosome-wide association significance in the discovery sample (OR = 0.81, 95% CI 0.73–0.89, P = 1.49 × 10−5). Combined analysis revealed rs5927056 for DMD gene with suggestive significance (P = 9.44 × 10−5). Moreover, the female-specific association of rs5933886 in ARHGAP6 gene (OR = 0.62, 95%CI: 0.47–0.81, P = 4.37 × 10−4) was successfully replicated in Taiwan Chinese (P = 1.64 × 10−2). rs5933886 also showed nominally significant gender × SNP interaction in both Guangdong (P = 6.25 × 10−4) and Taiwan datasets (P = 2.99 × 10−2). Conclusion Our finding reveals new susceptibility loci at the X chromosome conferring risk of NPC and supports the value of including the X chromosome in large-scale association studies.

Abstract 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.

Abstract Background Currently, mismatch repair-deficient (dMMR) status is a promising candidate for targeted immune checkpoint inhibition therapy in colorectal cancer (CRC) patients, however, the potential immunological mechanism has not yet been well clarified and some other predictors need to be excavated as well. Methods We collected 330 CRC patients by the match of mismatch repair-proficient (167) and dMMR (163), explored the relationship between MMR status and some important immune molecules including MHC class I, CD3, CD4, CD8, CD56, programmed death-1 and programmed death ligand-1, and investigated the risk factors for dMMR status as well as low MHC class I expression. The Pearson Chi square test was used for analyzing the associations between clinicopathological and immune characteristics and MMR status, and two categories logistic regression model was used for univariate and multivariate analysis to predict the odds ratio of risk factors for dMMR status and low MHC class I expression. Results Multivariate logistic regression analysis showed that low MHC class I and CD4 expression and high CD8 expression were significant risk factors for dMMR status [odds ratio (OR) = 24.66, 2.94 and 2.97, respectively; all p

Carboxymethyl konjac glucomannan (CMKGM) is an anionic derivative of konjac glucomannan (KGM). Its coacervation with ovalbumin (OVA) was investigated through turbidity and coacervate yield measurements and the resultant CMKGM-OVA coacervates were characterized as a function of phase separation pH. The results indicated that CMKGM could coacervate with OVA in pHs ranging from 2.0 to 4.5. OVA to CMKGM mass ratios higher than 1:1 led to insoluble coacervates, while lower ratios conferred soluble complexes. NaCl suppressed the interaction between CMKGM and OVA and could resuspend their precipitated coacervates. The interaction between the two polyelectrolytes was not affected in temperatures ranging from 25 °C to 55 °C, but was weakened in higher temperatures. The coacervation increased the thermal stability and induced structural changes in both the polyelectrolytes. Atomic force microscope observation revealed that the CMKGM-OVA coacervates separated in mass ratio 1:1 was not susceptible to aggregation, and quartz crystal microbalance with dissipation analysis demonstrated that OVA exhibited the strongest absorption towards CMKGM in pH 3.0 in multilayer mode. Hence, CMKGM is a promising polyelectrolyte for coacervation with proteins and could be used in the construction of targeted delivery systems through the electrostatic interaction with oppositely charged biopolymers. [ABSTRACT FROM AUTHOR]

BACKGROUND Angiotensin‐converting enzyme (ACE) inhibitory peptides are potential alternatives to the synthetic ACE inhibitory drugs, but the in vivo antihypertensive effects of most of them have not been confirmed. The tripeptide Leu‐Pro‐Pro (LPP) is one of the few peptides that have been proved clinically effective in reducing the blood pressure of hypertensive patients and casein is currently its major source. LPP is contained in multiple fractions of zein, and corn gluten meal (CGM) is hence a potential new source of LPP. For this purpose, CGM was fermented with a Lactobacillus helveticus strain and the medium composition was optimized; the decoloration of the resultant hydrolysate was investigated as well. RESULTS: LPP could be successfully released from CGM by fermentation with the strain Lactobacillus helveticus CICC 22536. The highest LPP content and protein recovery of 561 mg kg−1 and 14.92% occurred in the medium containing 20 g L−1 glucose, 15 g L−1 beef extract, 60 g L−1 CGM, 10 g L−1 CaCO3, 0.5 g L−1 NaCl, and inoculation amount 6%. The supplementation of Flavourzyme® further improved the two parameters to 662 mg kg−1 and 36.94%, respectively. The permeate of the hydrolysate after ultrafiltration through a 5 kDa membrane could be effectively decolored by the macroporous resin XAD‐16 without notable protein loss, and its LPP content was further boosted to 743 mg kg−1. CONCLUSION: CGM is a potential new source of LPP and its ultrafiltered and decolored hydrolysate could be used to develop new antihypertensive functional foods. © 2021 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

The application of whey protein isolate (WPI)–low methoxyl pectin (LMP) particles generated by complex coacervation as a food-grade high internal phase Pickering emulsion (HIPE) stabilizer was investigated. The coacervation pH greatly influenced the emulsification ability of the resultant WPI–LMP particles and those separated in pH 3.5 could generate a HIPE with oil fraction of up to 79.02%, which could be ascribed to their small particle size and moderate contact angle. The emulsification ability of the WPI–LMP coacervates was quite sensitive to ionic strength and their concentration, in which, HIPEs could be fabricated only in the absence of NaCl and stabilizer concentration 1.5% (w/v) or higher. The HIPEs showed decreased droplet size with WPI–LMP coacervate concentration rise and were of the oil-in-water type according to confocal laser scanning microscope observation. The HIPEs stabilized by the WPI–LMP coacervates were stable only in solutions with pH of 4.0 or lower and were resistant to centrifugation and heating, but collapsed readily upon freezing and thawing; meanwhile, a higher stabilizer concentration conferred better stabilities. Hence, the WPI–LMP coacervates could find potential applications in the food industry as a HIPE stabilizer. [ABSTRACT FROM AUTHOR]