Recombinant neutralizing secretory IgA antibodies for preventing mucosal acquisition and transmission of SARS-CoV-2.

Passive delivery of antibodies to mucosal sites may be a valuable adjunct to COVID-19 vaccination to prevent infection, treat viral carriage, or block transmission. Neutralizing monoclonal IgG antibodies are already approved for systemic delivery, and several clinical trials have been reported for delivery to mucosal sites where SARS-CoV-2 resides and replicates in early infection. However, secretory IgA may be preferred because the polymeric complex is adapted for the harsh, unstable external mucosal environment. Here, we investigated the feasibility of producing neutralizing monoclonal IgA antibodies against SARS-CoV-2. We engineered two class-switched mAbs that express well as monomeric and secretory IgA (SIgA) variants with high antigen-binding affinities and increased stability in mucosal secretions compared to their IgG counterparts. SIgAs had stronger virus neutralization activities than IgG mAbs and were protective against SARS-CoV-2 infection in an in vivo murine model. Furthermore, SIgA1 can be aerosolized for topical delivery using a mesh nebulizer. Our findings provide a persuasive case for developing recombinant SIgAs for mucosal application as a new tool in the fight against COVID-19.

Effect of mixed fermentation of Lactiplantibacillus plantarum and Lactiplantibacillus pentosus on phytochemical and flavor characteristics of Wallace melon juice.

BACKGROUND: Melons (Cucumis melo L.) are among the most commonly consumed fruits but they are highly susceptible to mechanical damage and rot during storage and transportation. New processed products are needed to avoid postharvest fruit loss and to increase health benefits. Fermentation is an effective means of utilizing the nutrients and improving flavor. RESULTS: Fermented melon juice (MJ) was prepared using three potential probiotics Lactiplantibacillus plantarum CICC21824 (LP), Lactiplantibacillus plantarum GB3-2 (LG), and Lactiplantibacillus pentosus XZ-34 (LX). The nutrition, flavor characteristics, and digestive properties of different fermented MJs were compared. The results demonstrated that, in comparison with mono-fermentation, mixed fermentation by LG and LX could increase the level of organic acids and phenolic acids. Correspondingly, antioxidant capacity was improved significantly and positively correlated with p-coumaric acid and cinnamic acid content. The production of alcohols and acids was more strongly enhanced by mixed culture fermentation, whereas mono-fermentation reduced the content of esters, especially ethyl acetate and isopropyl acetate. Aldehydes and ketones increased significantly in fermented MJ, and damascenone and heptanal could be the characteristic aroma compounds. CONCLUSION: Mixed fermented MJ provides more beneficial phytochemicals, better flavor, and stronger antioxidant properties than mono-fermentation. © 2024 Society of Chemical Industry.

Risk SNP-mediated LINC01614 upregulation drives head and neck squamous cell carcinoma progression via PI3K/AKT signaling pathway.

As potential biomarkers and therapeutic targets, long noncoding RNAs (lncRNAs) are involved in the tumorigenesis of various tumors. Genetic variation in long noncoding regions can lead to lncRNA dysfunction and even cancer. Nevertheless, studies on the association between lncRNA-associated single-nucleotide polymorphisms (SNPs) and the risk of head and neck squamous cell carcinoma (HNSCC) remain inadequate. Here, we aimed to explore the association between SNPs in LINC01614 and HNSCC risk, and the potential role of LINC01614 in tumorigenesis. In this study, we found that rs16854802 A > G (odds ratio [OR] = 1.42, 95% confidence interval [CI]: 1.22-1.77, p < 0.001) and rs3113503 G > C (OR = 1.38, 95% CI: 1.15-1.64, p < 0.001) in LINC01614 increased the risk of HNSCC in the Chinese population. Functional bioinformatic analysis and luciferase reporter assay revealed that rs3113503 G > C variant disrupted the binding of miRNA-616-3p to LINC01614, which resulted in the increased expression of LINC01614. Further analysis of the TCGA database demonstrated that the upregulated LINC01614 in HNSCC cancer tissues was associated with poor prognostic in HNSCC patients. In vitro experiments showed that knockdown of LINC01614 inhibited the proliferation, invasion, and migration ability of HNSCC cells. Mechanistically, allele C of rs3113503 in LINC01614 was more effective than allele G in activating the PI3K/AKT signaling pathway. Moreover, the reduced expression of LINC01614 also inhibited the activation of the PI3K/AKT signaling pathway. In summary, our findings revealed that the risk SNP rs3113503 G > C in LINC01614 altered the binding to miR-616-3p, which led to increased LINC01614 expression and promoted HNSCC progression by activating the PI3K/AKT signaling pathway.

Encapsulation of Zanthoxylum bungeanum essential oil to enhance flavor stability and inhibit lipid oxidation of Chinese-style sausage.

BACKGROUND: Zanthoxylum bungeanum essential oil (ZBEO) is a popular seasoning, commonly used in the food industry. It contains many easily degraded and highly volatile bioactive substances. Control of the stability of the bioactive substances in ZBEO is therefore very important in the food industry. RESULTS: In this study, microencapsulation was applied to improve ZBEO stability. The key parameters for microcapsule preparation were optimized by the Box-Behnken design method, and the optimum conditions were as follows: ratio of core to wall, 1:8; ratio of hydroxypropyl-α-cyclodextrin (HPCD) to soy protein isolate (SPI), 4; total solids content, 12%; and homogenization speed, 12 000 rpm. Antioxidant experiments have indicated that tea polyphenols (TPPs) effectively inhibited hydroxy-α-sanshool degradation in ZBEO microcapsules. Application of ZBEO microcapsules in Chinese-style sausage effectively inhibited lipid oxidation in sausages and protected hydroxy-α-sanshool and typical volatiles from volatilization and degradation during sausage storage. CONCLUSION: The results suggested that ZBEO microencapsulation is an effective strategy for improving the stability of its bioactive components and flavor ingredients during food processing. © 2022 Society of Chemical Industry.

Effect of cooking methods on the edible, nutritive qualities and volatile flavor compounds of rabbit meat.

BACKGROUND: Rabbit meat is a good edible meat source with high nutritional values. Cooking has a significant impact on the edible properties, nutritional qualities and flavor characteristics of meat. Studying the effect of cooking methods on rabbit meat qualities could encourage more understanding and acceptance of rabbit meat by consumers, and could also provide some reference for rabbit meat processing. Therefore, the effects of boiling, sous-vide cooking, steaming, microwaving, roasting, frying and pressure cooking on the edible, nutritive and volatile qualities of rabbit meat were investigated. RESULTS: The sous-vide cooked rabbit meat sample showed higher moisture content, water-holding capacity and lower cooking losses than other samples, but the results of roasted rabbit meat sample were the opposite, and scanning electron microscopy observations also verified the results. There was no significant difference in 2-thiobarbituric acid reactive substance (TBARS) value in the cooked samples except for roasting. Microwaving, roasting and frying exhibited stronger antioxidant activity than the other cooked samples after in vitro digestion. A total of 38 volatiles were identified in the cooked meat samples, and the samples were well divided into four groups by principal component analysis, and 13 volatiles were considered discriminatory variables for the cooked rabbit meat. CONCLUSION: The physicochemical characteristics of cooked meat differed significantly between the processing methods. Roasted meat showed lower TBARS value and stronger antioxidant activity after simulated digestion compared to the other meats. However, pressure cooked meat detected the most volatile components while roasting the least. © 2022 Society of Chemical Industry.

Complex wall materials of polysaccharide and protein effectively protected numb-taste substance degradation of Zanthoxylum bungeanum.

BACKGROUND: Hydroxyl-sanshools are mainly responsible for the numb taste and biological activities of Zanthoxylum bungeanum, but they show low water solubility, high volatility and easy degradation, which limit their application in the catering and food industries. Thus microcapsules of Z. bungeanum essential oil (ZBEO) were prepared to prevent numb-taste substance attenuation. RESULTS: The complex effects of hydroxypropyl-ß-cyclodextrin (HPCD) with other materials, such as konjac glucomannan octenyl succinate (KGOS), octenyl succinic anhydride-modified starch (OSAS), soy protein isolate (SPI) and gum arabic (GA), on the protection of the main numb-taste substance of ZBEO were investigated. Scanning electron microscopy and Fourier transform infrared spectroscopy analysis indicated that ZBEO was successfully encapsulated in the complex wall materials. X-ray diffraction indicated that the loaded essential oil did not affect the crystalline form of the wall material. The stability of the numb-taste substance α-sanshool in the microcapsules prepared with the complex microcapsule wall materials was higher than that in single-wall microcapsules. Storage stability evaluation indicated that microcapsules prepared with a combination of HPCD and SPI showed the greatest effect in maintaining the stability of the main numb-taste substance α-sanshool in ZBEO at room temperature, low pH and in high-salt conditions. CONCLUSION: Complex wall materials of polysaccharide and protein could effectively protect the numb-taste substance degradation of Z. bungeanum during processing and storage. © 2021 Society of Chemical Industry.

Combination of mutagenesis and adaptive evolution to engineer salt-tolerant and aroma-producing yeast for soy sauce fermentation.

BACKGROUND: The moromi fermentation of high-salt liquid-state fermentation (HLF) soy sauce is usually performed in high-brine solution (17-20%, w/w), which decreases the metabolic activity of aroma-producing yeast. To enhance the soy sauce flavors, increasing the salt tolerance of aroma-producing yeasts is very important for HLF soy sauce fermentation. RESULTS: In the present study, atmospheric and room-temperature plasma (ARTP) was first used to mutate the aroma-producing yeast Wickerhamomyces anomalus, and the salt tolerant strains were obtained by selection of synthetic medium with a sodium chloride concentration of 18% (w/w). Furthermore, adaptive laboratory evolution (ALE) was used to improve the salt tolerance of the mutant strains. The results obtained indicated that the combination use of ARTP and ALE markedly increased the NaCl tolerance of the yeast by increasing the cellular accumulation of K+ and removal of cytosolic Na+ , in addition to promoting the production of glycerin and strengthening the integrity of the cell membrane and cell wall. In soy sauce fermentation, the engineered strains improved the physicochemical parameters of HLF soy sauce compared to those produced by the wild-type strain, and the engineered strains also increased the alcohol, acid and aldehyde production, and enriched the types of esters in the soy sauce. CONCLUSION: The results of the present study indicated that the combination of ARTP mutagenesis and ALE significantly improved the salt tolerance of the aroma-producing yeast, and also enhanced the production of volatiles of HLF soy sauce. © 2021 Society of Chemical Industry.

PARP inhibitor Olaparib increases the sensitization to radiotherapy in FaDu cells.

Radioresistance causes a major problem for improvement of outcomes of patients treated with radiation. Targeting for DNA repair deficient mechanisms is a hallmark of sensitization to resistance. We tested whether Olaparib, a (poly) ADP-ribose polymerase (PARP) inhibitor, can sensitize the radioresistant FaDu cells to radiotherapy. Radioresistant FaDu cells, called FaDu-RR cells, were used as the radioresistant hypopharyngeal cancer models. The expression of PARP1 was detected in both FaDu and FaDu-RR cells. The role of Olaparib in radiosensitization was analysed with several assays including clonogenic cell survival, cell proliferation and cell cycle, and radioresistant xenograft. High expression of PARP1 had a significant effect on enhancing radioresistance in FaDu-RR cells compared with FaDu cells. After treatment of Olaparib, FaDu-RR cells showed significantly less and smaller surviving colonies, lower proliferation ability and G2/M arrest than those in the group without treatment. Moreover, Olaparib significantly reduced growth of tumours in FaDu-RR cell xenografts treated with ionizing radiation. Olaparib can significantly inhibit PARP1 expression and consequently has significant effects on radiosensitization in FaDu-RR cells. These results indicate that Olaparib may help individualize treatment and improve their outcomes of hypopharyngeal cancer patients treated with radiation.

Novel mutagenesis and screening technologies for food microorganisms: advances and prospects.

Microorganisms are indispensable in the food industry, but wild-type strains hardly meet the current industrial demands due to several undesirable traits. Therefore, microbial strain improvement offers a critical solution to enhance the food industry. Traditional techniques for food microbial improvement, such as the use of chemical mutagens and manual isolation/purification, are inefficient, time-consuming, and laborious, restricting further progress in the area of food fermentation. In this review, the applications of novel mutagenesis and screening technologies used for the improvement of food microbes were summarized, including random mutagenesis based on physical irradiation, microbial screening facilitated by a microtiter plate, fluorescence-activated cell or droplet sorting, and microscaled fermentation in a microtiter plate or microbioreactor. In comparison with conventional methods, these new tools have the potential in accelerating microbial strain improvement and their combined applications could create a new trend for strain development. However, several problems that could affect its potential application may include the following: the lack of specific mutagenesis devices and biosensing systems, the insufficient improvement of the mixed culture system, the low efficiency when using filamentous fungi and flocculating bacteria, and the insufficient safety assessment on harnessing genome-editing technology. Therefore, future works on strain improvement remain challenging for the food industry.

Factors associated with death outcome in patients with severe coronavirus disease-19 (COVID-19): a case-control study.

Rationale: Up to date, the exploration of clinical features in severe COVID-19 patients were mostly from the same center in Wuhan, China. The clinical data in other centers is limited. This study aims to explore the feasible parameters which could be used in clinical practice to predict the prognosis in hospitalized patients with severe coronavirus disease-19 (COVID-19). Methods: In this case-control study, patients with severe COVID-19 in this newly established isolation center on admission between 27 January 2020 to 19 March 2020 were divided to discharge group and death event group. Clinical information was collected and analyzed for the following objectives: 1. Comparisons of basic characteristics between two groups; 2. Risk factors for death on admission using logistic regression; 3. Dynamic changes of radiographic and laboratory parameters between two groups in the course. Results: 124 patients with severe COVID-19 on admission were included and divided into discharge group (n=35) and death event group (n=89). Sex, SpO2, breath rate, diastolic pressure, neutrophil, lymphocyte, C-reactive protein (CRP), procalcitonin (PCT), lactate dehydrogenase (LDH), and D-dimer were significantly correlated with death events identified using bivariate logistic regression. Further multivariate logistic regression demonstrated a significant model fitting with C-index of 0.845 (p<0.001), in which SpO2≤89%, lymphocyte≤0.64×109/L, CRP>77.35mg/L, PCT>0.20µg/L, and LDH>481U/L were the independent risk factors with the ORs of 2.959, 4.015, 2.852, 3.554, and 3.185, respectively (p<0.04). In the course, persistently lower lymphocyte with higher levels of CRP, PCT, IL-6, neutrophil, LDH, D-dimer, cardiac troponin I (cTnI), brain natriuretic peptide (BNP), and increased CD4+/CD8+ T-lymphocyte ratio and were observed in death events group, while these parameters stayed stable or improved in discharge group. Conclusions: On admission, the levels of SpO2, lymphocyte, CRP, PCT, and LDH could predict the prognosis of severe COVID-19 patients. Systematic inflammation with induced cardiac dysfunction was likely a primary reason for death events in severe COVID-19 except for acute respiratory distress syndrome.

Comparative review and the recent progress in detection technologies of meat product adulteration.

Meat adulteration, mainly for the purpose of economic pursuit, is widespread and leads to serious public health risks, religious violations, and moral loss. Rapid, effective, accurate, and reliable detection technologies are keys to effectively supervising meat adulteration. Considering the importance and rapid advances in meat adulteration detection technologies, a comprehensive review to summarize the recent progress in this area and to suggest directions for future progress is beneficial. In this review, destructive meat adulteration technologies based on DNA, protein, and metabolite analyses and nondestructive technologies based on spectroscopy were comparatively analyzed. The advantages and disadvantages, application situations of these technologies were discussed. In the future, determining suitable indicators or markers is particularly important for destructive methods. To improve sensitivity and save time, new interdisciplinary technologies, such as biochips and biosensors, are promising for application in the future. For nondestructive techniques, convenient and effective chemometric models are crucial, and the development of portable devices based on these technologies for onsite monitoring is a future trend. Moreover, omics technologies, especially proteomics, are important methods in laboratory detection because they enable multispecies detection and unknown target screening by using mass spectrometry databases.

Clinical and imaging characteristics of subacute combined degeneration complicated with white matter lesions in the brain: a report of five cases.

PURPOSE: To report five cases of subacute combined degeneration (SCD) with brain involvement and explore its clinical and imaging characteristics. METHODS: A retrospective study was performed on the clinical data and brain MRI of five patients with subacute combined degeneration with brain involvement (out of 107 cases with SCD in total). White matter lesions (WML) assessment was performed qualitatively using Fazekas scale score. RESULTS: The main symptoms in four patients were weakness in both lower extremities and unstable walking (limb weakness in three patients, dizziness in three patients, and blurred vision in one patient). One patient had memory loss and cognitive dysfunction. The MMSE scale indicated mild dementia in one patient. On head MRI (Magnetic Resonance Imaging), multifocal and symmetrical high signals of T2WI and FLAIR were observed in the frontal lobe and periventricular white matter in four patients, while another patient showed preferential atrophy in frontal regions. Fazekas scale scores ranged from 1-6. CONCLUSION: Adult subacute combined degeneration seldom involves the brain. Multifocal and symmetrical high signal white matter lesions can be found on FLAIR and T2WI, as well as frontal atrophy on head MRI.

Konjac glucomannan octenyl succinate (KGOS) as an emulsifier for lipophilic bioactive nutrient encapsulation.

BACKGROUND: Konjac glucomannan octenyl succinate (KGOS) has excellent emulsification properties and can potentially be used in the food industry as an emulsifier, stabilizer and microcapsule wall material. In the present study, the in vitro digestion properties and emulsification capability and stability of KGOS were studied to evaluate the transport and encapsulation characteristics of KGOS with insoluble bioactive nutrients. RESULTS: Confocal scanning laser microscopy (CSLM) suggested that oil droplets could be encapsulated by KGOS into regular spheres. In vitro digestion properties showed that KGOS is effective for colon-targeted transport. ß-Carotene was selected as a representative lipophilic bioactive compound to evaluate the emulsification characteristics of KGOS. The loading capacity of the 0.4 mg mL-1 KGOS solution for ß-carotene was 3.26%, and transmission electron microscopy suggested that the self-aggregate particles of KGOS/ß-carotene (KGOSC) were more uniform than KGOS. With a composition of 0.03% ß-carotene, 0.3% KGOS and 10% medium-chain triglycerides, the emulsification yield of the KGOSC nanoemulsion was more than 95%. After 30 days of storage, the particle size and polydispersity index of the KGOSC nanoemulsion were less than 5 nm and 0.5, respectively, and the sensitivity of KGOSC nanoemulsions to storage conditions decreased in the order temperature, oxygen and light. CONCLUSION: The results of this study suggested that KGOS is a good potential emulsifier and stabilizer for lipophilic bioactive nutrient encapsulation. © 2018 Society of Chemical Industry.

A functional variant at the miRNA binding site in E2F1 gene is associated with risk and tumor HPV16 status of oropharynx squamous cell carcinoma.

Human papillomavirus (HPV) activates E2F1-driven transcription via the E7-RB1-E2F pathway. Genetic polymorphisms in the 3' untranslated region (UTR) targeted by miRNAs can affect the regulation of target genes and individual cancer risk. Thus, we hypothesized that a polymorphism at the 3'UTR miRNA binding site of E2F1 gene (rs3213180) was associated with risk of oral squamous cell carcinoma (OSCC) and tumor HPV status of oropharynx squamous cell carcinoma (OPSCC). We determined the E2F1rs3213180 polymorphism and HPV16 L1 serology of 325 OSCC patients and 335 controls, and tumor HPV16 status of 552 OPSCC. Logistic regression models were used to calculate associations of E2F1rs3213180 polymorphism with risk of HPV-associated OSCC and tumor HPV status of OPSCC. The risk of HPV-associated OSCC was modified by the E2F1rs3213180 polymorphism. Patients with both HPV seropositivity and the Ins/Del or Ins/Ins genotype of E2F1rs3213180 had the highest risk of OSCC, while the lowest risk was detected in patients with HPV seronegativity and the Del/Del genotype. A similar and more prominent effect was detected in OPSCC, but not in oral cavity squamous cell carcinoma (OCSCC) patients. Notably, that effect trend was pronounced in never-smokers and never-drinkers. Furthermore, the patients with the E2F1rs3213180 Ins/Del or Ins/Ins genotype were 2.9 times more likely to have HPV-positive tumors than those with the Del/Del genotype. Our results suggest that the E2F1rs3213180 polymorphism may influence susceptibility to HPV-associated OSCC, particularly for OPSCC, never-smokers and never-drinkers, but not for patients with OCSCC. Additional larger population and functional studies are warranted to confirm our findings. © 2016 Wiley Periodicals, Inc.

E2F transcription factor 2 variants as predictive biomarkers for recurrence risk in patients with squamous cell carcinoma of the oropharynx.

Because E2F transcription factor 2 (E2F2) promoter polymorphisms have been implicated in carcinogenesis and prognosis, we investigated associations between genetic variants in five E2F2 promoter polymorphisms and recurrence risk of squamous cell carcinoma of the oropharynx (SCCOP) in 1 008 patients. A log-rank test and multivariable Cox models were used to assess the associations. Compared with patients with variant genotypes of E2F2-rs2742976 and E2F2-rs3218123, patients with common homozygous genotypes had better disease-free survival (both log-rank, P < 0.001) and lower SCCOP recurrence risk (HR, 0.4, 95% CI, 0.3-0.6 and HR, 0.3, 95% CI, 0.2-0.5, respectively) after multivariable adjustment. Furthermore, among patients with HPV16-positive tumors, those with common homozygous genotypes of E2F2-rs2742976 and E2F2-rs3218123 had better disease-free survival rates (both log-rank, P < 0.001) and lower recurrence risk (HR, 0.1, 95% CI, 0.1-0.4 and HR, 0.1, 95% CI, 0.0-0.2, respectively) than patients with variant genotypes. However, no significant differences were found for the other three polymorphisms. After combining the risk genotypes of the five polymorphisms and using the high-risk group (2-5 risk genotypes) as the reference group, we found that the low-risk groups (0 or 1 risk genotype) had significantly lower recurrence risk among all patients (HR, 0.4, 95% CI, 0.3-0.6) and among HPV16-positive patients (HR, 0.2, 95% CI, 0.1-0.5). Our findings suggest that E2F2 polymorphisms may individually or jointly modify SCCOP recurrence risk, particularly for SCCOP patients with HPV16-positive tumors. © 2017 Wiley Periodicals, Inc.

Transcriptome changes in adaptive evolution of xylose-fermenting industrial Saccharomyces cerevisiae strains with δ-integration of different xylA genes.

It is of utmost importance to construct industrial xylose-fermenting Saccharomyces cerevisiae strains for lignocellulosic bioethanol production. In this study, two xylose isomerase-based industrial S. cerevisiae strains, O7 and P5, were constructed by δ-integration of the xylose isomerase (XI) gene xylA from the fungus Orpinomyces sp. and from the bacterium Prevotella ruminicola, respectively. The xylose consumption of the strains O7 and P5 at 48-h fermentation was 17.71 and 26.10 g/L, respectively, in synthetic medium with xylose as the sole sugar source. Adaptive evolution further improved the xylose fermentation capacity of the two strains to 51.0 and 28.9% in average, respectively. The transcriptomes of these two strains before and after evolution were analyzed using RNA-Seq. The expression levels of the genes involved in cell integrity, non-optimal sugar utilization, and stress response to environment were significantly up-regulated after evolution and did not depend on the origin of xylA; the expression levels of the genes involved in transmembrane transport, rRNA processing, cytoplasmic translation, and other processes were down-regulated. The expression of genes involved in central carbon metabolism was fine-tuned after the evolution. The analysis of transcription factors (TFs) indicated that most of the genes with significant differential expression were regulated by the TFs related to cell division, DNA damage response, or non-optimal carbon source utilization. The results of this study could provide valuable references for the construction of efficient xylose-fermenting XI strains.

Effect of human papillomavirus seropositivity and E2F2 promoter variants on risk of squamous cell carcinomas of oropharynx and oral cavity.

Given roles of HPV and genetic factors in cancer risk, we evaluated associations of HPV16 seropositivity and five E2F2 promoter variants with squamous cell carcinoma of oropharynx (SCCOP) and squamous cell carcinoma of oral cavity (SCCOC) risk in a case-control study of 325 patients and 335 cancer-free matched controls. We found that HPV16 seropositivity was significantly associated with SCCOP risk (aOR, 5.4, 95%CI, 3.7-8.9) but not SCCOC (aOR, 0.8, 95%CI, 0.4-1.5), while each E2F2 polymorphism had no significant main effect on SCCOP and SCCOC risk. However, after combining HPV serological status and E2F2 promoter variants together, the modification effect of HPV serology and individual or combined risk genotypes of five polymorphisms on risk was significantly higher among SCCOP than among SCCOC. Furthermore, the stratified analysis by smoking status showed that all such modifying effects aforementioned on SCCOP were more pronounced in never smokers than in smokers. These findings are in agreement with those of previous studies, in which a majority of SCCOP were caused by HPV infection, whereas most SCCOC were found to be caused by smoking and drinking. Taken together, these findings indicate that the risk of SCCOP as opposed to SCCOC associated with HPV16 seropositivity was modified by E2F2 promoter variants either individually or jointly, especially in never smokers.

Xylose fermentation efficiency and inhibitor tolerance of the recombinant industrial Saccharomyces cerevisiae strain NAPX37.

Industrial yeast strains with good xylose fermentation ability and inhibitor tolerance are important for economical lignocellulosic bioethanol production. The flocculating industrial Saccharomyces cerevisiae strain NAPX37, harboring the xylose reductase-xylitol dehydrogenase (XR-XDH)-based xylose metabolic pathway, displayed efficient xylose fermentation during batch and continuous fermentation. During batch fermentation, the xylose consumption rates at the first 36 h were similar (1.37 g/L/h) when the initial xylose concentrations were 50 and 75 g/L, indicating that xylose fermentation was not inhibited even when the xylose concentration was as high as 75 g/L. The presence of glucose, at concentrations of up to 25 g/L, did not affect xylose consumption rate at the first 36 h. Strain NAPX37 showed stable xylose fermentation capacity during continuous ethanol fermentation using xylose as the sole sugar, for almost 1 year. Fermentation remained stable at a dilution rate of 0.05/h, even though the xylose concentration in the feed was as high as 100 g/L. Aeration rate, xylose concentration, and MgSO4 concentration were found to affect xylose consumption and ethanol yield. When the xylose concentration in the feed was 75 g/L, a high xylose consumption rate of 6.62 g/L/h and an ethanol yield of 0.394 were achieved under an aeration rate of 0.1 vvm, dilution rate of 0.1/h, and 5 mM MgSO4. In addition, strain NAPX37 exhibited good tolerance to inhibitors such as weak acids, furans, and phenolics during xylose fermentation. These findings indicate that strain NAPX37 is a promising candidate for application in the industrial production of lignocellulosic bioethanol.

Hexokinase 2 overexpression promotes the proliferation and survival of laryngeal squamous cell carcinoma.

Proliferating cancer cells preferentially use anaerobic glycolysis rather than oxidative phosphorylation for energy production. Hexokinase 2 (HK2) is highly expressed in many malignant cells and is necessary for anaerobic glycolysis. The role of HK2 in laryngeal squamous cell carcinoma (LSCC) is unknown. In this study, the expression of HK2 in LSCC was investigated and the effect of inhibiting HK2 expression with small hairpin RNA (shRNA) on tumor growth was investigated. Using immunohistochemistry, HK2 expression was assessed in LSCC tissues. Human laryngeal carcinoma Hep-2 cells were stably transfected with a plasmid expressing HK2 shRNA (pGenesil-1.1-HK2) and were compared to control cells with respect to the cell cycle, cell viability, apoptosis, and their ability to form xenograft tumors. HK2 expression was significantly higher in LSCC than in papilloma or glottis polypus. Tumor samples of higher T, N, and TNM stage often had stronger HK2 staining. HK2 shRNA reduced HK2 mRNA, protein levels, and HK activity in Hep-2 cells. HK2 cells expressing shRNA demonstrated a higher G0-G1 ratio, increased apoptosis, and reduced viability. Xenograft tumors derived from cells expressing HK2 shRNA were smaller and had lower proliferation than those from untransfected or control-plasmid-transfected cells. In conclusion, depletion of HK2 expression resulted in reduced xenograft tumor development likely by reducing proliferation, altering the cell cycle, reducing cell viability and activating apoptosis. These data suggest that HK2 plays an important role in the development of LSCC and represents a potential therapeutic target for LSCC.

Synergistic effects of TAL1 over-expression and PHO13 deletion on the weak acid inhibition of xylose fermentation by industrial Saccharomyces cerevisiae strain.

In the industrial production of bioethanol from lignocellulosic biomass, a strain of Saccharomyces cerevisiae that can ferment xylose in the presence of inhibitors is of utmost importance. The recombinant, industrial-flocculating S. cerevisiae strain NAPX37, which can ferment xylose, was used as the parent to delete the gene encoding p-nitrophenylphosphatase (PHO13) and overexpress the gene encoding transaldolase (TAL1) to evaluate the synergistic effects of these two genes on xylose fermentation in the presence of weak acid inhibitors, including formic, acetic, or levulinic acids. TAL1 over-expression or PHO13 deletion improved xylose fermentation as well as the tolerance of NAPX37 to all three weak acids. The simultaneous deletion of PHO13 and the over-expression of TAL1 had synergistic effects and improved ethanol production and reduction of xylitol accumulation in the absence and presence of weak acid inhibitors.