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Background: There is a rapidly increasing incidence of early-onset colorectal cancer (EO-CRC) which threatens the survival of young people, while aging also represents a challenging clinical problem. Objectives: We aimed to investigate the differences in the clinical characteristics and prognosis in stage III rectal cancer (RC), to help optimize treatment strategies. Design and methods: This study included 757 patients with stage III RC, all of whom received neoadjuvant chemoradiotherapy and total mesorectal excision. The whole cohort was categorized as very early onset (VEO, ⩽30 years old), early onset (EO, >30 years old, ⩽50 years old), intermediate onset (IO, >50 years, ⩽70 years), or late onset (LO, >70 years old). Results: There were more female VEO patients than males, more mucinous adenocarcinoma, signet-ring cell carcinoma, pre-treatment cT4 stage, and higher pre-treatment serum carbohydrate antigen 19-9 compared with the other three groups. VEO patients had the worst survival with the highest RC-related mortality (34.5%), recurrence (13.8%), and metastasis (51.7%). LO patients had the highest non-RC-related mortality rate (16.6%). The Cox regression model showed VEO was a negative independent prognostic factor for disease-free survival [DFS, hazard ratio (HR): 2.830, 95% confidence interval (CI): 1.633–4.904, p < 0.001], distant metastasis-free survival (DMFS, HR: 2.969, 95% CI: 1.720–5.127, p < 0.001), overall survival (OS, HR: 2.164, 95% CI: 1.102–4.249, p = 0.025), and cancer-specific survival (CSS, HR: 2.321, 95% CI: 1.145–4.705, p = 0.020). LO was a negative independent factor on DFS (HR: 1.800, 95% CI: 1.113–2.911, p = 0.017), DMFS (HR: 1.903, 95% CI: 1.150–3.149, p = 0.012), OS (HR: 2.856, 95% CI: 1.745–4.583, p < 0.001), and CSS (HR: 2.248, 95% CI: 1.282–3.942, p = 0.005). VEO patients had better survival in the total neoadjuvant therapy-like (TNT-like) pattern on DFS ( p = 0.039). IO patients receiving TNT-like patterns had better survival on DFS, OS, and CSS ( p = 0.006, p = 0.018, p = 0.006, respectively). Conclusion: In stage III RC, VEO patients exhibited unique clinicopathological characteristics, with VEO a negative independent prognostic factor for DFS, DMFS, OS, and CSS. VEO and IO patients may benefit from a TNT-like treatment pattern.

Abstract Background Standard treatment of locally advanced rectal cancer (LARC) was neoadjuvant chemoradiotherapy (CRT), followed by total mesorectal excision (TME). Total neoadjuvant treatment (TNT), a new concept, attempts to deliver both systemic chemotherapy and neoadjuvant CRT prior to surgery. Patients treated with neoadjuvant chemotherapy were more likely to show higher tumor regression. The objective of this trial was to increase complete clinical rate (cCR) for LARC patients by optimizing tumor response, using TNT regimen as compared to conventional chemoradiotherapy. TESS, a prospective, open‐label, multicenter, single‐arm, phase 2 study, is underway. Methods Main inclusion criteria include cT3‐4aNany or cT1‐4aN+ rectal adenocarcinoma aged 18‐70y; Eastern Cooperative Oncology Group (ECOG) performance 0–1; location ≤5 cm from anal verge. Ninety‐eight patients will receive 2 cycles of neoadjuvant chemotherapy Capeox (capecitabine + oxaliplatin) before, during, and after radiotherapy 50Gy/25 fractions, before TME (or other treatment decisions, such as Watch and Wait strategy) and adjuvant chemotherapy capecitabine 2 cycles. Primary endpoint is the cCR rate. Secondary endpoints include ratio of sphincter preservation strategy; pathological complete response rate and tumor regression grade distribution; local recurrence or metastasis; disease‐free survival; locoregional recurrence‐free survival; acute toxicity; surgical complications; long‐term anal function; late toxicity; adverse effect, ECOG standard score, and quality of life. Adverse events are graded per Common Terminology Criteria for Adverse Events V5.0. Acute toxicity will be monitored during antitumor treatment, and late toxicity will be monitored for 3 years from the end of the first course of antitumor treatment. Discussion The TESS trial aims to explore a new TNT strategy, which is expected to increase the rate of cCR and sphincter preservation rate. This study will provide new options and evidence for a new sandwich TNT strategy in patients with distal LARC.

BackgroundThe pathological T3N0M0 (pT3N0M0) rectal cancer is the earliest stage and has the best prognosis in the locally advanced rectal cancer, but the optimal treatment remains controversial. A reliable prognostic model is needed to discriminate the high-risk patients from the low-risk patients, and optimize adjuvant chemotherapy (ACT) treatment decisions by predicting the likelihood of ACT benefit for the target population.Patients and methodsWe gathered and analyzed 276 patients in Sun Yat-sen University Cancer Center from March 2005 to December 2011. All patients underwent total mesorectal excision (TME), without preoperative therapy, and were pathologically proven pT3N0M0 rectal cancer with negative circumferential resection margin (CRM). LASSO regression model was used for variable selection and risk factor prediction. Multivariable cox regression was used to develop the predicting model. Optimum cut-off values were determined using X-Tile plot analysis. The 10-fold cross-validation was adopted to validate the model. The performance of the nomogram was evaluated with its calibration, discrimination and clinical usefulness.ResultsA total of 188 patients (68.1%) had ACT and no patients had adjuvant radiotherapy. Age, monocyte percentage, carbohydrate antigen 19–9, lymph node dissection numbers and perineural invasion (PNI) were identified as significantly associated variables that could be combined for an accurate prediction risk of Cancer Specific Survival (CSS) for pT3N0M0 patients. The model adjusted for CSS showed good discrimination with a C-index of 0.723 (95% CI: 0.652–0.794). The calibration curves showed that the nomogram adjusted for CSS was able to predict 3-, 5-, and 10-year CSS accurately. The corresponding predicted probability was used to stratify high and low-risk patients (10-year CSS: 69.1% vs. 90.8%, HR = 3.815, 95%CI: 2.102–6.924, P < 0.0001). ACT improved overall survival (OS) in the low-risk patients (10-year OS: 91.9% vs. 83.3%, HR = 0.338, 95% CI: 0.135–0.848, P < 0.0001), while it did not exhibit a significant benefit in the high-risk patients.ConclusionThe present study showed that age, monocyte percentage, carbohydrate antigen 19–9, lymph node dissection numbers and PNI were independent prognostic factors for pT3N0M0 rectal cancer patients. A nomogram based on these prognostic factors effectively predicts CSS in patients, which can be conveniently used in clinical practice. ACT may improve overall survival in the low-risk patients. But the benefit of ACT was not seen in the high-risk patients.

Volumetric resorption of the alveolar ridge often occurs in both horizontal and vertical directions following tooth extraction. There is a specific lack of evidence for alveolar ridge reconstruction at molar and premolar sites with severe bone resorption. This randomized controlled trial used 3D and linear analyses to evaluate volumetric changes of the alveolar bone following alveolar ridge reconstruction (ARR) at molar and premolar sites with severe bone resorption as compared to unassisted socket healing before implant placement. A total of 31 patients (15 men, 16 women) with > 50% hard tissue loss in one or more socket walls were recruited and randomized into either a test group (postextraction ARR using deproteinized bovine bone mineral with 10% collagen [DBBM-C] and platelet-rich fibrin [PRF] with a resorbable collagen membrane) or a control group (natural healing after extraction). The clinical, linear, and volumetric implant-related and patient-reported outcomes were analyzed after 4 months of healing. Linear bone assessments revealed significantly greater ridge width gains in the test group (25% in the mesial, midfacial, and distal aspects) and less reduction of vertical bone ridge than in the control group (P < .05). Further, volumetric bone remodeling was significantly higher in the test group (35.1% ± 34.9% for ARR, 14.2% ± 12.8% for control; P < .05). Patient-reported discomfort and keratinized mucosal changes were comparable between groups. ARR with a combination of DBBM-C, PRF, and a resorbable membrane at posterior sites with a severe socket wall deficiency (> 50% bone loss) is a safe and more capable therapeutic method when compared to natural healing and unassisted sockets. Collectively, the present analyses demonstrate that ARR represents an efficient method to maintain and augment crestal bone at posterior extraction sites with severe bone defects when assessed after 4 months of healing. [ABSTRACT FROM AUTHOR]

Abstract Foodstuff is a complex system that consists of a variety of nutrients. Protein is the basis of human life and health, which is made up of amino acids combined in different proportional orders. Polyphenols are a class of small molecule active substances with strong pro‐life health effects. It has been found that protein and polyphenols can be combined by covalent and non‐covalent interactions to form complex delivery carriers. The interaction between the two can effectively improve the physiological activities of proteins and enhance the bio‐accessibility of polyphenols. With the maturation of ultrasound technology, several studies have shown that ultrasound can promote the production of protein−polyphenol complexes. To promote the study of protein–polyphenol interactions in foodstuff by ultrasound technology, the preparation methods of protein−polyphenol complexes, the effects of ultrasound on complex generation, and analytical methods were systematically summarized based on an extensive literature review, and further research directions were proposed. It provides the reference for the ultrasound study of protein−polyphenol complexes.

Abstract Background Gamma (γ)-Aminobutyric acid (GABA) as a bioactive compound is used extensively in functional foods, pharmaceuticals and agro-industry. It can be biosynthesized via decarboxylation of monosodium glutamate (MSG) or L-glutamic acid (L-Glu) by glutamate decarboxylase (GAD; EC4.1.1.15). GADs have been identified from a variety of microbial sources, such as Escherichia coli and lactic acid bacteria. However, no GADs from Streptomyces have been characterized. The present study is aimed to identify new GADs from Streptomyces strains and establish an efficient bioproduction platform for GABA in E. coli using these enzymes. Results By sequencing and analyzing the genomes of three Streptomyces strains, three putative GADs were discovered, including StGAD from Streptomyces toxytricini NRRL 15443, SsGAD from Streptomyces sp. MJ654-NF4 and ScGAD from Streptomyces chromofuscus ATCC 49982. The corresponding genes were cloned from these strains and heterologously expressed in E. coli BL21(DE3). The purified GAD proteins showed a similar molecular mass to GadB from E. coli BL21(DE3). The optimal reaction temperature is 37 °C for all three enzymes, while the optimum pH values for StGAD, SsGAD and ScGAD are 5.2, 3.8 and 4.2, respectively. The kinetic parameters including V max , Km, k cat and k cat /Km values were investigated and calculated through in vitro reactions. SsGAD and ScGAD showed high biocatalytic efficiency with k cat /Km values of 0.62 and 1.21 mM− 1·s− 1, respectively. In addition, engineered E. coli strains harboring StGAD, SsGAD and ScGAD were used as whole-cell biocatalysts for production of GABA from L-Glu. E. coli/SsGAD showed the highest capability of GABA production. The cells were repeatedly used for 10 times, with an accumulated yield of 2.771 kg/L and an average molar conversion rate of 67% within 20 h. Conclusions Three new GADs have been functionally characterized from Streptomyces, among which two showed higher catalytic efficiency than previously reported GADs. Engineered E. coli harboring SsGAD provides a promising cost-effective bioconversion system for industrial production of GABA.

This study investigated the effect of milk oligopeptides and (α)-tocopherol on inhibition of linoleic acid oxidation using Fe2+-vitamin C induced linoleic acid oxidation model through analysis of malondialdehyde, peroxide value, and conjugated diene and triene in the model. The alteration of milk oligopeptides maximal absorption wavelength, fluorescent feature, and secondary structure were further investigated to elucidate the interactions between milk oligopeptide and (α)-tocopherol that altered the inhibitory effect of linoleic acid oxidation. Results showed that Pro-Tyr-Tyr-Ala-Lys (PYYAK) and Ile-Pro-Ile-Gln-Tyr (IPIQY) with (α)-tocopherol significantly inhibited the oxidation of linoleic acid and reduced the formation of malondialdehyde by 38% and 41%, respectively. Additionally, Ile-Pro-Ile-Gln-Tyr-Val (IPIQYV) and (α)-tocopherol synergistically reduced the peroxide value in the model by 36.8%. Milk oligopeptides exhibited a blue shift on its maximal absorption wavelength, and their absorbance value decreased with the increase of the (α)-tocopherol concentration. The fluorescent intensity of milk oligopeptides was reduced with the addition of (α)-tocopherol and such fluorescent intensity reductions resulted from the static quenching process through the formation of milk oligopeptide-(α)-tocopherol complex. Fourier transform infrared spectroscopy analysis revealed that (α)-tocopherol significantly altered the secondary structure of milk oligopeptides and the percentage of β-turn obviously increased in milk oligopeptide-(α)-tocopherol complex. These indicated that the inhibition of linoleic acid oxidation might result from complex formed between milk oligopeptide and (α)-tocopherol through inter-molecular interactions.

The pH, thermal, urea, and trifluoroethanol treatments were used to denature yogurt antioxidant peptides, and their antioxidant capacities and secondary structures were analysed. Results showed that yogurt peptides treated at pH 6.0 or above 50°C exhibited higher antioxidant activity than the control, whereas trifluoroethanol treatment resulted in a reduction and urea treatment held invariability. Peptide secondary configuration analyses revealed that these treated peptides significantly decreased their α-helical conformation but enhanced the β-sheet presence as well as an obvious alteration on β-turn and random coil structures. These peptide conformation alterations contributed to their antioxidant property increase.

grobacterium-mediated T-DNA transfer has been proven to be an efficient strategy for insertional mutagenesis and elucidation of gene function in filamentous fungi. The implementation of large-scale T-DNA insertional mutagenesis requires the development of high-efficient transformation and high-throughput screening procedures. Here, using green fluorescent protein (GFP) as a vital marker, a highly efficient T-DNA-based mutagenesis and screening system was developed in Trichoderma reesei. The uridine auxotrophic T. reesei M23 as the host was transformed with A. tumefaciens EH105 strain harboring a binary vector pC-OEP, which beared the pyrG gene for primary selection on minimal medium without uridine and the egfp gene for fluorescence-based rapid screening of the mitotically stable transformants. The efficiency of transformation was up to 10-20 transformants per 10 target conidia. Microscopic examination revealed strong GFP expression and fluorescence emission in conidia, growing hyphae and mycelia. An effective and convenient screening procedure using 96-well plates and multilabel counter for fluorescence intensity counting was developed to rapidly identify the T-DNA tagged T. reesei mutants. Furthermore, the presence of T-DNA integration at random sites in the genome was confirmed by Southern blot analysis. This report of the T-DNA-based mutagenesis and rapid screening system using GFP as a vital reporter provides a promising strategy to speeding up the genome-scale T-DNA insertional mutagenesis and functional genomics analysis of this cellulolytic fungus T. reesei. [ABSTRACT FROM AUTHOR]

This study investigated the phenolic compounds of 15 Chrysanthemum morifolium Ramat cv. ‘Hangbaiju’, including 6 ‘Duoju’ and 9 ‘Taiju’, using high performance liquid chromatography (HPLC). The antioxidant activities of these ‘Hangbaiju’ were estimated by DPPH, ABTS and FRAP assays. Results show that a total of 14 phenolic compounds were detected in these flowers, including 3 mono-caffeoylquinic acids, 3 di-caffeoylquinic acids, 1 phenolic acid and 7 flavonoids. ‘Duoju’ and ‘Taiju’ possess different concentrations of phenolic compounds, and ‘Taiju’ exhibits higher caffeoylquinic acids and stronger antioxidant activities than ‘Duoju’. Caffeoylquinic acids show a strong correlation with the antioxidant activities of the samples. Principal component analysis (PCA) reveals an obvious separation between ‘Duoju’ and ‘Taiju’, using phenolic compounds as variables. Apigenin-7-O-glucoside, 3,5-di-O-caffeoylquinic acid, luteolin and acacetin were found to be the key phenolic compounds to differentiate ‘Duoju’ from ‘Taiju’.

The article presents a study which showed that cystathione β-synthase (CBS), compared with cystathionine γ-lyase, is the major enzyme that synthesizes hydrogen sulfide in the pathogenic fungus Candida (C.) albicans. Topics include participation of both CBS and CSE in hydropersulfidation, deletion of CBS on mitochondrial dysfunction in C. albicans, and the crystal structure of C. albicans CBS.