The potential of glycinin basic peptide derived from soybean as a promising candidate for the natural food additive and preservative: A review.

Glycinin basic peptide (GBP) is the basic polypeptide of soybean glycinin that is isolated using cheap and readily available raw materials (soybean meals). GBP can bear high-temperature processing and has good functional properties, such as emulsification and adhesion properties et al. GBP exhibits broad-spectrum antimicrobial activities against Gram-positive and Gram-negative bacteria as well as fungi. Beyond that, GBP shows enormous application potential to improve the quality and extend the shelf life of food products. This review will systematically provide information on the purification, physicochemical and functional properties of GBP. Moreover, the antimicrobial activities and multi-target antimicrobial mechanism of GBP as well as the applications of GBP in different food products are also reviewed and discussed in detail. This review aims to offer valuable insights for the applications of GBP in the food industry as a promising natural food additive and preservative.

The Effect of Physical Therapy on Somatosensory Tinnitus.

Objective: The objective of this work was to assess the effect of physical therapy in patients with somatosensory tinnitus (ST) and explore the influence of physical therapy on clinical variables obtained before treatment. Methods: A total of 43 patients with ST were randomized to the immediate-start group (n = 20) and delayed-start group (n = 23). All patients received physical therapy for 1 week (seven sessions). Each session lasted 60 min. The Visual Analogue Scale (VAS), Tinnitus Handicap Inventory (THI), and numerical pain rating scale (NPRS) scores were documented at baseline and after treatment (week 1) for all patients. For subjects in the immediate-start group, the THI, VAS, and NPRS scores were measured after therapy (weeks 6, 9, and 12, respectively). Medical history characteristic functional activity scale (HCFA) scores were measured at baseline to assess the association between somatic symptoms and tinnitus. Results: At week 1, VAS, THI, and NPRS scores of patients in the immediate-start group were improved by 1.25 ± 1.59, 11.10 ± 15.10, and 0.95 ± 1.54 points, respectively, and were significantly higher than those in the delayed-start group (p < 0.05). The change in VAS, THI, and NPRS scores in the treatment group was significantly positively correlated with the scores of the HCFA before treatment (r = 0.786, p < 0.001; r = 0.680, p = 0.001; r = 0.796, p < 0.001). There was no significant difference in THI, VAS, and NPRS scores among patients in the immediate-start group between weeks 1, 6, 9, and 12 after treatment (p > 0.05). Conclusions: Although more participants were necessary in the further study, the study implies that physical therapy can reduce physical pain, improve tinnitus symptoms, and quality of life in ST patients without hearing loss, and the short-term curative effect is stable, especially for tinnitus patients with clear somatic symptoms.

Construction of CDKN2A-related competitive endogenous RNA network and identification of GAS5 as a prognostic indicator for hepatocellular carcinoma.

BACKGROUND: Competitive endogenous RNA (ceRNA) is an innovative way of gene expression modulation, which plays a crucial part in neoplasia. However, the intricacy and behavioral characteristics of the ceRNA network in hepatocellular carcinoma (HCC) remain dismal. AIM: To establish a cyclin dependent kinase inhibitor 2A (CDKN2A)-related ceRNA network and recognize potential prognostic indicators for HCC. METHODS: The mutation landscape of CDKN2A in HCC was first explored using the cBioPortal database. Differential expression analysis was implemented between CDKN2Ahigh and CDKN2Alow expression HCC samples. The targeted microRNAs were predicted by lncBasev3.0, and the targeted mRNAs were predicted by miRDB, and Targetscan database. The univariate and multivariate analysis were utilized to identify independent prognostic indicators. RESULTS: CDKN2A was frequently mutated and deleted in HCC. The single-cell RNA-sequencing analysis revealed that CDKN2A participated in cell cycle pathways. The CDKN2A-related ceRNA network-growth arrest specific 5 (GAS5)/miR-25-3p/SRY-box transcription factor 11 (SOX11) was successfully established. GAS5 was recognized as an independent prognostic biomarker, whose overexpression was correlated with a poor prognosis in HCC patients. The association between GAS5 expression and methylation, immune infiltration was explored. Besides, traditional Chinese medicine effective components targeting GAS5 were obtained. CONCLUSION: This CDKN2A-related ceRNA network provides innovative insights into the molecular mechanism of HCC formation and progression. Moreover, GAS5 might be a significant prognostic biomarker and therapeutic target in HCC.

The use of amino acids and their derivates to mitigate against pesticide-induced toxicity.

Exposure to pesticides induces oxidative stress and deleterious effects on various tissues in non-target organisms. Numerous models investigating pesticide exposure have demonstrated metabolic disturbances such as imbalances in amino acid levels within the organism. One potentially effective strategy to mitigate pesticide toxicity involves dietary intervention by supplementing exogenous amino acids and their derivates to augment the body's antioxidant capacity and mitigate pesticide-induced oxidative harm, whose mechanism including bolstering glutathione synthesis, regulating arginine-NO metabolism, mitochondria-related oxidative stress, and the open of ion channels, as well as enhancing intestinal microecology. Enhancing glutathione synthesis through supplementation of substrates N-acetylcysteine and glycine is regarded as a potent mechanism to achieve this. Selection of appropriate amino acids or their derivates for supplementation, and determining an appropriate dosage, are of the utmost importance for effective mitigation of pesticide-induced oxidative harm. More experimentation is required that involves large population samples to validate the efficacy of dietary intervention strategies, as well as to determine the effects of amino acids and their derivates on long-term and low-dose pesticide exposure. This review provides insights to guide future research aimed at preventing and alleviating pesticide toxicity through dietary intervention of amino acids and their derivates.

Structure, functional and physicochemical properties of lotus seed protein under different pH environments.

BACKGROUND: The present study investigated the structure, functional and physicochemical properties of lotus seed protein (LSP) under different pH environments. The structures of LSP were characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, Fourier transform infrared spectroscopy (FTIR), zeta potential, particle size distributions, free sulfhydryl and rheological properties. The functional and physicochemical properties of LSP were characterized by color, foaming property, emulsification property, solubility, oil holding capacity, water holding capacity, differential scanning calorimetry analysis and surface hydrophobicity. RESULTS: LSP was mainly composed of eight subunits (18, 25, 31, 47, 51, 56, 65 and 151 kDa), in which the richest band was 25 kDa. FTIR results showed that LSP had high total contents of α-helix and ß-sheet (44.81-46.85%) in acidic environments. Meanwhile, there was more ß-structure and random structure in neutral and alkaline environments (pH 7.0 and 9.0). At pH 5.0, LSP had large particle size (1576.98 nm), high emulsion stability index (91.43 min), foaming stability (75.69%) and water holding capacity (2.21 g g-1), but low solubility (35.98%), free sulfhydryl content (1.95 µmol g-1) and surface hydrophobicity (780). DSC analysis showed the denaturation temperatures (82.23 °C) of LSP at pH 5.0 was higher than those (80.10, 80.52 and 71.82 °C) at pH 3.0, 7.0 and 9.0. The analysis of rheological properties showed that LSP gel had high stability and great strength in an alkaline environment. CONCLUSION: The findings of the present study are anticipated to serve as a valuable reference for the implementation of LSP in the food industry. © 2024 Society of Chemical Industry.

Diagnostic accuracy of magnetically guided capsule endoscopy with a detachable string for detecting oesophagogastric varices in adults with cirrhosis: prospective multicentre study.

OBJECTIVE: To evaluate the diagnostic accuracy and safety of using magnetically guided capsule endoscopy with a detachable string (ds-MCE) for detecting and grading oesophagogastric varices in adults with cirrhosis. DESIGN: Prospective multicentre diagnostic accuracy study. SETTING: 14 medical centres in China. PARTICIPANTS: 607 adults (>18 years) with cirrhosis recruited between 7 January 2021 and 25 August 2022. Participants underwent ds-MCE (index test), followed by oesophagogastroduodenoscopy (OGD, reference test) within 48 hours. The participants were divided into development and validation cohorts in a ratio of 2:1. MAIN OUTCOME MEASURES: The primary outcomes were the sensitivity and specificity of ds-MCE in detecting oesophagogastric varices compared with OGD. Secondary outcomes included the sensitivity and specificity of ds-MCE for detecting high risk oesophageal varices and the diagnostic accuracy of ds-MCE for detecting high risk oesophagogastric varices, oesophageal varices, and gastric varices. RESULTS: ds-MCE and OGD examinations were completed in 582 (95.9%) of the 607 participants. Using OGD as the reference standard, ds-MCE had a sensitivity of 97.5% (95% confidence interval 95.5% to 98.7%) and specificity of 97.8% (94.4% to 99.1%) for detecting oesophagogastric varices (both P<0.001 compared with a prespecified 85% threshold). When using the optimal 18% threshold for luminal circumference of the oesophagus derived from the development cohort (n=393), the sensitivity and specificity of ds-MCE for detecting high risk oesophageal varices in the validation cohort (n=189) were 95.8% (89.7% to 98.4%) and 94.7% (88.2% to 97.7%), respectively. The diagnostic accuracy of ds-MCE for detecting high risk oesophagogastric varices, oesophageal varices, and gastric varices was 96.3% (92.6% to 98.2%), 96.9% (95.2% to 98.0%), and 96.7% (95.0% to 97.9%), respectively. Two serious adverse events occurred with OGD but none with ds-MCE. CONCLUSION: The findings of this study suggest that ds-MCE is a highly accurate and safe diagnostic tool for detecting and grading oesophagogastric varices and is a promising alternative to OGD for screening and surveillance of oesophagogastric varices in patients with cirrhosis. TRIAL REGISTRATION: ClinicalTrials.gov NCT03748563.

Predicting Severity in Hypertriglyceridemia-Induced Acute Pancreatitis: The Role of Neutrophils, Calcium, and Apolipoproteins.

BACKGROUND Hypertriglyceridemia-induced acute pancreatitis (HTG-AP), representing 10% of all acute pancreatitis cases, is characterized by younger onset age and more severe progression, often leading to higher ICU admission rates. This condition poses a significant challenge due to its rapid progression and the potential for severe complications, including multiple organ failure. HTG-AP is distinct from other forms of pancreatitis, such as those caused by cholelithiasis or alcohol, in terms of clinical presentation and outcomes. It's essential to identify early markers that can predict the severity of HTG-AP to improve patient management and outcomes. MATERIAL AND METHODS This study divided 127 HTG-AP patients into mild acute pancreatitis (MAP, n=71) and moderate-to-severe acute pancreatitis (MSAP/SAP, n=56) groups. Blood biological indicators within the first 24 hours of admission were analyzed. Risk factors for HTG-AP progression were determined using binary logistic regression and ROC curves. RESULTS Elevated levels of HCT, NLR, TBI, DBI, AST, Cre, and AMS were noted in the MSAP/SAP group, with lower levels of LYM, Na⁺, Ca²âº, ApoA, and ApoB compared to the MAP group (p<0.05). NEUT%, Ca²âº, ApoA, and ApoB were significantly linked with HTG-AP severity. Their combined ROC analysis yielded an area of 0.81, with a sensitivity of 61.8% and specificity of 90%. CONCLUSIONS NEUT%, Ca²âº, ApoA, and ApoB are significant risk factors for progressing to MSAP/SAP in HTG-AP. Their combined assessment provides a reliable predictive measure for early intervention in patients at risk of severe progression.

Structure, physicochemical properties, and biological activities of protein hydrolysates from Zanthoxylum seed.

BACKGROUND: Zanthoxylum seed, as a low-cost and easily accessible plant protein resource, has good potential in the food industry. But protein and its hydrolysates from Zanthoxylum seed are underutilized due to the dearth of studies on them. This study aimed to investigate the structure and physicochemical and biological activities of Zanthoxylum seed protein (ZSP) hydrolysates prepared using Protamex®, Alcalase®, Neutrase®, trypsin, or pepsin. RESULTS: Hydrolysis using each of the five enzymes diminished average particle size and molecular weight of ZSP but increased random coil content. ZSP hydrolysate prepared using pepsin had the highest degree of hydrolysis (24.07%) and the smallest molecular weight (<13 kDa) and average particle size (129.80 nm) with the highest solubility (98.9%). In contrast, ZSP hydrolysate prepared using Alcalase had the highest surface hydrophobicity and foaming capacity (88.89%), as well as the lowest foam stability (45.00%). Moreover, ZSP hydrolysate prepared using Alcalase exhibited the best hydroxyl-radical scavenging (half maximal inhibitory concentration (IC50 ) 1.94 mg mL-1 ) and ferrous-ion chelating (IC50 0.61 mg mL-1 ) activities. Additionally, ZSP hydrolysate prepared using pepsin displayed the highest angiotensin-converting enzyme inhibition activity (IC50 0.54 mg mL-1 ). CONCLUSION: These data showed that enzyme hydrolysis improved the physicochemical properties of ZSP, and enzymatic hydrolysates of ZSP exhibited significant biological activity. These results provided validation for application of ZSP enzymatic hydrolysates as antioxidants and antihypertensive agents in the food or medicinal industries. © 2023 Society of Chemical Industry.

Functional Connectivity Alterations and Molecular Characterization of the Anterior Cingulate Cortex in Tinnitus Pathology without Hearing Loss.

Compared with individuals with hearing loss, tinnitus patients without hearing loss have more psychological or emotional problems. Tinnitus is closely associated to abnormal metabolism and function of the limbic system, a key brain region for emotion experience, but the underlying molecular mechanism remains unknown. Using whole-brain microvasculature dynamics imaging, the anterior cingulate cortex (ACC) is identified as a key brain region of limbic system involve in the onset of salicylate-induced tinnitus in mice. In the tinnitus group, there is enhanced purine metabolism, oxidative phosphorylation, and a distinct pattern of phosphorylation in glutamatergic synaptic pathway according to the metabolome profiles, quantitative proteomic, and phosphoproteomic data of mice ACC tissue. Electroencephalogram in tinnitus patients with normal hearing thresholds show that the functional connectivity between pregenual anterior cingulate cortex and the primary auditory cortex is significantly increased for high-gamma frequency band, which is positively correlated with the serum glutamate level. These findings indicate that ACC plays an important role in the pathophysiology of tinnitus by interacting with the primary auditory cortex and provide potential molecular targets in the ACC for tinnitus treatment.

Distal tibiofibular syndesmosis fibular notch typing and its clinical significance based on CT / 解剖学报

Objective To investigate the morphological typing and clinical significance of the distal tibiofibular syndesmosis fibular notch based on CT images. Methods According to the inclusion and exclusion ceiteria‚ the imaging data of patients undergoing ankle joint CT examination were analyzed‚ and the inferior tibiofibular joint fibula notch was classified according to the morphological characteristics. The measurements included 8 distances. There were 123 males and 102 females‚ all of whom were Han nationality‚ aged 18-60 years old. Results Retrospectively analyzed the result of 225 patients from December 2013 to December 2022. The distal tibiofibular syndesmosis fibular notch was divided into four types according to morphological characteristics‚ C-shaped (50. 67%)‚ V-shaped (26. 67%)‚ flat-shaped (15. 11%) and L-shaped (7. 56%). The angle between the anterior and posterior facets of the flat shape (145. 56 ± 9. 25)° was the largest and the angle between the anterior and posterior facets of the L shape (125. 07 ± 13. 54)° was the smallest(P< 0. 05); the depth of the notch in the flat shape (3. 11 ± 0. 83) mm was the smallest and in the L shape (4. 47±1. 11) mm was the largest(P<0. 05);The posterior facet length (13. 06 ± 3. 56) mm and anterior tibiofibular gap (3. 83±1. 49) mm on left were larger than on the right side (P<0. 05); The posterior facet length (13. 36 ± 3. 46) mm‚ fibular notch depth (3. 93 ± 1. 10) mm and vertical distance of tibiofibular overlap (9. 10 ± 2. 55) mm larger in men than in women (P<0. 05). Conclusion In this study‚ the data related to the inferior tibiofibular syndesmosis notch were measured and divided into four types according to the shape. The flat inferior tibiofibular syndesmosis notch is more likely to have chronic ankle instability‚ and the fibula is more likely to move forward during anatomical reduction. The inferior tibiofibular syndesmosis of L-shaped and C-shaped notches is more prone to posterior displacement of fibula or poor rotation reduction during anatomical reduction.

The structural characteristics and physicochemical properties of mung bean protein hydrolysate of protamex induced by ultrasound.

BACKGROUND: The limited physicochemical properties (such as low foaming and emulsifying capacity) of mung bean protein hydrolysate restrict its application in the food industry. Ultrasound treatment could change the structures of protein hydrolysate to accordingly affect its physicochemical properties. The aim of this study was to investigate the effects of ultrasound treatment on the structural and physicochemical properties of mung bean protein hydrolysate of protamex (MBHP). The structural characteristics of MBHP were evaluated using tricine sodium dodecylsulfate-polyacrylamide gel electrophoresis, laser scattering, fluorescence spectrometry, etc. Solubility, fat absorption capacity and foaming, emulsifying and thermal properties were determined to characterize the physicochemical properties of MBHP. RESULTS: MBHP and ultrasonicated-MBHPs (UT-MBHPs) all contained five main bands of 25.8, 12.1, 5.6, 4.8 and 3.9 kDa, illustrating that ultrasound did not change the subunits of MBHP. Ultrasound treatment increased the contents of α-helix, ß-sheet and random coil and enhanced the intrinsic fluorescence intensity of MBHP, but decreased the content of ß-turn, which demonstrated that ultrasound modified the secondary and tertiary structures of MBHP. UT-MBHPs exhibited higher solubility, foaming capacity and emulsifying properties than MBHP, among which MBHP-330 W had the highest solubility (97.32%), foaming capacity (200%), emulsification activity index (306.96 m2 g-1 ) and emulsion stability index (94.80%) at pH 9.0. CONCLUSION: Ultrasound treatment enhanced the physicochemical properties of MBHP, which could broaden its application as a vital ingredient in the food industry. © 2023 Society of Chemical Industry.

Predicting longitudinal brain atrophy in Parkinson's disease using a Susceptible-Infected-Removed agent-based model.

Parkinson's disease is a progressive neurodegenerative disorder characterized by accumulation of abnormal isoforms of alpha-synuclein. Alpha-synuclein is proposed to act as a prion in Parkinson's disease: In its misfolded pathologic state, it favors the misfolding of normal alpha-synuclein molecules, spreads trans-neuronally, and causes neuronal damage as it accumulates. This theory remains controversial. We have previously developed a Susceptible-Infected-Removed (SIR) computational model that simulates the templating, propagation, and toxicity of alpha-synuclein molecules in the brain. In this study, we test this model with longitudinal MRI collected over 4 years from the Parkinson's Progression Markers Initiative (1,068 T1 MRI scans, 790 Parkinson's disease scans, and 278 matched control scans). We find that brain deformation progresses in subcortical and cortical regions. The SIR model recapitulates the spatiotemporal distribution of brain atrophy observed in Parkinson's disease. We show that connectome topology and geometry significantly contribute to model fit. We also show that the spatial expression of two genes implicated in alpha-synuclein synthesis and clearance, SNCA and GBA, also influences the atrophy pattern. We conclude that the progression of atrophy in Parkinson's disease is consistent with the prion-like hypothesis and that the SIR model is a promising tool to investigate multifactorial neurodegenerative diseases over time.

Multiple test procedures of disease prevalence based on stratified partially validated series in the presence of a gold standard.

This paper discusses the problem of disease prevalence in clinical studies, focusing on multiple comparisons based on stratified partially validated series in the presence of a gold standard. Five test statistics, including two Wald-type test statistics, the inverse hyperbolic tangent transformation test statistic, likelihood ratio test statistic, and score test statistic, are proposed to conduct multiple comparisons. To control the overall type I error rate, several adjustment procedures are developed, namely the Bonferroni, Single-step adjusted MaxT, Single-step adjusted MinP, Holm's Step-down, and Hochberg's step-up procedures, based on these test statistics. The performance of the proposed methods is evaluated through simulation studies in terms of the empirical type I error rate and empirical power. Simulation results show that the Single-step adjusted MaxT procedure and Single-step adjusted MinP procedure generally outperform the other three procedures, and these two test procedures based on all test statistics have satisfactory performance. Notably, the Single-step adjusted MinP procedure tends to exhibit higher empirical power than the Single-step adjusted MaxT procedure. Furthermore, the Step-down and Step-up procedures show greater power compared to the Bonferroni method. The study also observes that as the validated ratio increases, the empirical type I errors of all test procedures approach the nominal level while maintaining higher power. Two real examples are presented to illustrate the proposed methods.

Yinlai Decoction Protects Microstructure of Colon and Regulates Serum Level of D-Lactic Acid in Pneumonia Mice Fed with High-Calorie and High-Protein Diet.

OBJECTIVE: To investigate the effect of Yinlai Decoction (YD) on the microstructure of colon, and activity of D-lactic acid (DLA) and diamine oxidase (DAO) in serum of pneumonia mice model fed with high-calorie and high-protein diet (HCD). METHODS: Sixty male Kunming mice were randomly divided into 6 groups by the random number table method: normal control, pneumonia, HCD, HCD with pneumonia (HCD-P), YD (229.2 mg/mL), and dexamethasone (15.63 mg/mL) groups, with 10 in each group. HCD mice were fed with 52% milk solution by gavage. Pneumonia mice was modeled with lipopolysaccharide inhalation and was fed by gavage with either the corresponding therapeutic drugs or saline water, twice daily, for 3 days. After hematoxylin-eosin staining, the changes in the colon structure were observed under light microscopy and transmission electron microscope, respectively. Enzyme-linked immunosorbent assay was used to detect the protein levels of DLA and DAO in the serum of mice. RESULTS: The colonic mucosal structure and ultrastructure of mice in the normal control group were clear and intact. The colonic mucosal goblet cells in the pneumonia group tended to increase, and the size of the microvilli varied. In the HCD-P group, the mucosal goblet cells showed a marked increase in size with increased secretory activity. Loose mucosal epithelial connections were also observed, as shown by widened intercellular gaps with short sparse microvilli. These pathological changes of intestinal mucosa were significantly reduced in mouse models with YD treatment, while there was no significant improvement after dexamethasone treatment. The serum DLA level was significantly higher in the pneumonia, HCD, and HCD-P groups as compared with the normal control group (P<0.05). Serum DLA was significantly lower in the YD group than HCD-P group (P<0.05). Moreover, serum DLA level significantly increased in the dexamethasone group as compared with the YD group (P<0.01). There was no statistical significance in the serum level of DAO among groups (P>0.05). CONCLUSIONS: YD can protect function of intestinal mucosa by improving the tissue morphology of intestinal mucosa and maintaining integrity of cell connections and microvilli structure, thereby reducing permeability of intestinal mucosa to regulate the serum levels of DLA in mice.

Detection of Antibiotic Resistance in Feline-Origin ESBL Escherichia coli from Different Areas of China and the Resistance Elimination of Garlic Oil to Cefquinome on ESBL E. coli.

The development of drug-resistance in the opportunistic pathogen Escherichia coli has become a global public health concern. Due to the share of similar flora between pets and their owners, the detection of pet-origin antibiotic-resistant E. coli is necessary. This study aimed to detect the prevalence of feline-origin ESBL E. coli in China and to explore the resistance elimination effect of garlic oil to cefquinome on ESBL E. coli. Cat fecal samples were collected from animal hospitals. The E. coli isolates were separated and purified by indicator media and polymerase chain reaction (PCR). ESBL genes were detected by PCR and Sanger sequencing. The MICs were determined. The synergistic effect of garlic oil and cefquinome against ESBL E. coli was investigated by checkerboard assays, time-kill and growth curves, drug-resistance curves, PI and NPN staining, and a scanning electronic microscope. A total of 80 E. coli strains were isolated from 101 fecal samples. The rate of ESBL E. coli was 52.5% (42/80). The prevailing ESBL genotypes in China were CTX-M-1, CTX-M-14, and TEM-116. In ESBL E. coli, garlic oil increased the susceptibility to cefquinome with FICIs from 0.2 to 0.7 and enhanced the killing effect of cefquinome with membrane destruction. Resistance to cefquinome decreased with treatment of garlic oil after 15 generations. Our study indicates that ESBL E. coli has been detected in cats kept as pets. The sensitivity of ESBL E. coli to cefquinome was enhanced by garlic oil, indicating that garlic oil may be a potential antibiotic enhancer.

Changes in quality components and antioxidant activity of peony seed soy sauce during low-salt solid-state fermentation.

BACKGROUND: In this study, the fermentation conditions of peony seed soy sauce (PSSS) koji were optimized by response surface method, and the quality components and antioxidant activity of PSSS were investigated at different low-salt solid-state fermentation stages. RESULTS: Results of response surface method showed that the optimal fermentation conditions were 460.6 g kg-1 water content, 48.6 h culture time, 31.5 °C culture temperature and ratio 2.1:1 (w/w) of peony seed meal:wheat bran, with the highest neutral protease activity (2193.78 U g-1 ) of PSSS koji. PSSS had the highest amino acid nitrogen (7.69 g L-1 ), salt-free soluble solids (185.26 g L-1 ), total free amino acids (49.03 g L-1 ), essential free amino acids (19.58 g L-1 ) and umami free amino acids (16.64 g L-1 ) at 20 days of fermentation. The highest total phenolics were 5.414 g gallic acid equivalent L-1 and total flavonoids 0.617 g rutin equivalent L-1 , as well as the highest DPPH radical scavenging activity (86.19%) and reducing power (0.8802, A700 ) of PSSS fermented at 30 days. Sensory evaluation showed that fermentation of 20 days and 25 days could produce a better taste and aroma of PSSS than 15 days and 30 days. CONCLUSION: PSSS had the highest quality components in the middle of fermentation (20 days) and the highest antioxidant activity in the late fermentation period (30 days). These results demonstrated that peony seed meal could be used to produce high-quality soy sauce with high antioxidant activity. © 2023 Society of Chemical Industry.

Detection of antibiotic-resistant canine origin Escherichia coli and the synergistic effect of magnolol in reducing the resistance of multidrug-resistant Escherichia coli.

Background: The development of antimicrobial resistance in the opportunistic pathogen Escherichia coli has become a global public health concern. Due to daily close contact, dogs kept as pets share the same E. coli with their owners. Therefore, the detection of antimicrobial resistance in canine E. coli is important, as the results could provide guidance for the future use of antibiotics. This study aimed to detect the prevalence of antibiotic-resistance of canine origin E. coli in Shaanxi province and to explore the inhibition effect of magnolol combined with cefquinome on MDR E. coli, so as to provide evidence for the use of antibiotics. Methods: Canine fecal samples were collected from animal hospitals. The E. coli isolates were separated and purified using various indicator media and polymerase chain reaction (PCR). Drug-resistance genes [aacC2, ant(3')-I, aph(3')-II, aac(6')-Ib-cr, aac(3')-IIe, bla KPC , bla IMP-4 , bla OXA , bla CMY , bla TEM-1 , bla SHV , bla CTX-M-1 , bla CTX-M-9 , Qnra, Qnrb, Qnrs, TetA, TetB, TetM, Ermb] were also detected by PCR. The minimum inhibitory concentration (MIC) was determined for 10 antibiotics using the broth-microdilution method. Synergistic activity of magnolol and cefquinome against multidrug-resistant (MDR) E. coli strains was investigated using checkerboard assays, time-kill curves, and drug-resistance curves. Results: A total of 101 E. coli strains were isolated from 158 fecal samples collected from animal hospitals. MIC determinations showed that 75.25% (76/101) of the E. coli strains were MDR. A total of 22 drug-resistance genes were detected among the 101 strains. The bla TEM-1gene exhibited the highest detection rate (89.77%). The TetA and Sul gene also exhibited high detection rate (66.34 and 53.47%, respectively). Carbapenem-resistant E. coli strains were found in Shangluo and Yan'an. Additionally, in MDR E. coli initially resistant to cefquinome, magnolol increased the susceptibility to cefquinome, with an FICI (Fractional Inhibitory Concentration Index) between 0.125 and 0.5, indicating stable synergy. Furthermore, magnolol enhanced the killing effect of cefquinome against MDR E. coli. Resistance of MDR E. coli to cefquinome decreased markedly after treatment with magnolol for 15 generations. Conclusion: Our study indicates that antibiotic-resistance E. coli has been found in domestic dogs. After treatment with magnolol extracted from the Chinese herb Houpo (Magnolia officinalis), the sensitivity of MDR E. coli to cefquinome was enhanced, indicating that magnolol reverses the resistance of MDR E. coli. The results of this study thus provide reference for the control of E. coli resistance.

Supervised Phenotype Discovery From Multimodal Brain Imaging.

Data-driven discovery of image-derived phenotypes (IDPs) from large-scale multimodal brain imaging data has enormous potential for neuroscientific and clinical research by linking IDPs to subjects' demographic, behavioural, clinical and cognitive measures (i.e., non-imaging derived phenotypes or nIDPs). However, current approaches are primarily based on unsupervised approaches, without the use of information in nIDPs. In this paper, we proposed a semi-supervised, multimodal, and multi-task fusion approach, termed SuperBigFLICA, for IDP discovery, which simultaneously integrates information from multiple imaging modalities as well as multiple nIDPs. SuperBigFLICA is computationally efficient and largely avoids the need for parameter tuning. Using the UK Biobank brain imaging dataset with around 40,000 subjects and 47 modalities, along with more than 17,000 nIDPs, we showed that SuperBigFLICA enhances the prediction power of nIDPs, benchmarked against IDPs derived by conventional expert-knowledge and unsupervised-learning approaches (with average nIDP prediction accuracy improvements of up to 46%). It also enables the learning of generic imaging features that can predict new nIDPs. Further empirical analysis of the SuperBigFLICA algorithm demonstrates its robustness in different prediction tasks and the ability to derive biologically meaningful IDPs in predicting health outcomes and cognitive nIDPs, such as fluid intelligence and hypertension.

To compare the efficacy and incidence of severe hematological adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia / 中华血液学杂志

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.

Clinical efficacy and safety of venetoclax combined with multidrug chemotherapy in the treatment of 15 patients with relapsed or refractory early T-cell precursor acute lymphoblastic leukemia / 中华血液学杂志

Objective: To explore the efficacy and safety of Venetoclax combined with multidrug chemotherapy in patients with relapsed or refractory early T-cell precursor acute lymphoblastic leukemia (R/R ETP-ALL) . Methods: This study retrospectively analyzed 15 patients with R/R ETP-ALL who received Venetoclax combined with multidrug chemotherapy from December 2018 to February 2022. Among them, eight cases were combined with demethylated drugs, four cases were combined with demethylated drugs and HAAG chemotherapy regimen, two cases were combined with demethylated drugs and CAG regimen, and one case was combined with Cladribine. Specific usage and dosage of Venetoclax: 100 mg on day 1, 200 mg on day 2, 400 mg on day 3-28, orally; when combined with azole antifungal drugs, dosage was reduced to 100 mg/d. Results: Fifteen patients (10 males and 5 females) with R/R ETP-ALL were treated with Venetoclax and multidrug chemotherapy with a median age of 35 (12-42) years old. Of 4 refractory and 11 relapsed patients, the efficacy was evaluated on the 21th day following combined chemotherapy: the overall response rate, the complete response (CR) rate, and the CR with incomplete hematological recovery (CRi) rate were 67.7% (10/15), 60.0% (9/15), and 6.7% (1/15), respectively. For the overall study population, the 12-month overall survival (OS) rate was 60.0%, and the median OS was 17.7 months. The disease-free survival (DFS) rate of all CR patients at 12 months was 60.0%, and the median DFS did not reach. About 14 patients had Ⅲ-Ⅳ hematological toxicity, but these adverse reactions were all controllable. No adverse reaction in the nervous system and tumor lysis syndrome occurred in this study, and no adverse reaction of organs above grade Ⅲ occurred. Conclusion: Venetoclax combined with multidrug chemotherapy may be a safe and promising treatment option for patients with R/R ETP-ALL.