Two-step modification of pullulanase and transglucosidase: A novel way to improve the gel strength and reduce the digestibility of rice starch.

The multiscale structure, gel strength and digestibility of rice starch modified by the two-step modification of pullulanase (PUL) pretreatment and transglucosidase (TG) treatment for 6, 12, 18 and 24 h were investigated. The debranching hydrolysis of PUL produced some linear chains, which rearranged to form stable crystalline structures, reducing the digestible starch content, but weakening the gel strength. TG treatment connected some short chains to longer linear chains via α-1,6-glycosidic bonds, generating the structures of linear chain with fewer branches. The short branches promoted the interaction between starch molecules to form a more compact three-dimensional gel network structure, showing higher hardness and springiness. Moreover, these chains could form more stable crystals, reducing the digestible starch content, and the increase of branching degree inhibited digestive enzyme hydrolysis, reducing the digestion rate. The multiscale structure of starch tended to stabilize after TG treatment for 18 h, which could form a gel with stronger strength and lower digestibility than native starch gel. Therefore, the two-step modification of PUL and TG was an effective way to change the structure of rice starch to improve the gel strength and reduce the digestibility.

Associations of maternal serum concentration of iron-related indicators with birth outcomes in Chinese: a pilot prospective cohort study.

BACKGROUND: Previous studies of maternal iron and birth outcomes have been limited to single indicators that do not reflect the comprehensive relationship with birth outcomes. We aimed to investigate the relationship between maternal iron metabolism and neonatal anthropometric indicators using comprehensive iron-related indicators. METHODS: A total of 914 Chinese mother-child dyads were enrolled in this prospective study. Subjects' blood samples were collected at ≤ 14 weeks of gestation. Serum concentrations of iron-related indicators were measured by enzyme-linked immunosorbent assay (ELISA). Femur length was measured by B-ultrasound nearest delivery. Neonatal anthropometric indicators were collected from medical records. RESULTS: After adjustment for potential covariates, higher iron (per one standard deviation, SD increase) was detrimentally associated with - 0.22 mm lower femur length, whereas higher transferrin (per one SD increase) was associated with 0.20 mm higher femur length. Compared with normal subjects (10th-90th percentiles), subjects with extremely high (> 90th percentile) iron concentration were detrimentally associated with lower femur length, birth weight, and chest circumference, and a higher risk of low birth weight, LBW (HR: 3.92, 95%CI: 1.28, 12.0). Subjects with high concentration of soluble transferrin receptor, sTFR and transferrin (> 90th percentile) were associated with higher femur length. Subjects with low concentration of iron and ferritin concentrations (< 10th percentile) were associated with a higher risk of LBW (HR: 4.10, 95%CI: 1.17, 14.3) and macrosomia (HR: 2.79, 95%CI: 1.06, 7.35), respectively. CONCLUSIONS: Maternal iron overload in early pregnancy may be detrimentally associated with neonatal anthropometric indicators and adverse birth outcomes.

Associations of early pregnancy serum uric acid levels with risk of gestational diabetes and birth outcomes: a retrospective cohort study.

BACKGROUND: Previous evidence suggests that higher blood uric acid (UA) levels are associated with adverse cardiovascular outcomes during pregnancy and subsequent birth outcomes. However, it has been relatively unclear whether these associations persist in normotensive pregnant women. METHODS: The study was based on a retrospective analysis of 18,250 mother-infant pairs in a large obstetric center in China. Serum UA concentrations in early pregnancy (median: 17.6, IQR: 16.3, 18.6 gestational weeks) were assessed. Hyperuricemia was defined as ≥ one standard deviation (SD) of the reference value for the corresponding gestational age. Outcomes of gestational diabetes mellitus (GDM), preterm birth (PB), low birth weight (LBW), macrosomia, small for gestational age (SGA) and large for gestational age (LGA) were extracted from the medical records. RESULTS: The mean maternal UA level was 0.22 ± 0.05 mmol/L, and 2,896 (15.9%) subjects had hyperuricemia. After adjustment for several covariates, UA was associated with several adverse outcomes. The ORs (95%CI) per one SD increase in serum UA concentration were 1.250 (1.136, 1.277) for GDM, 1.137 (1.060, 1.221) for PB, 1.134 (1.051, 1.223) for LBW, and 1.077 (1.020, 1.137) for SGA, respectively. Similar adverse associations were found between hyperuricemia and GDM, PB (ORs: 1.394 and 1.385, P < 0.001), but not for LBW, macrosomia, SGA, and LGA. Adverse associations tended to be more pronounced in subjects with higher BMI for outcomes including PB, LBW, and SGA (P interaction = 0.001-0.028). CONCLUSION: Higher UA levels in early pregnancy were associated with higher risk of GDM, PB, LBW, and SGA in normotensive Chinese women.

Associations of Dietary Anthocyanidins Intake with Bone Health in Children: A Cross-Sectional Study.

PURPOSE: Bone health and body composition share several common mechanisms like oxidative stress and inflammation. Anthocyanins have antioxidant and anti-inflammatory properties. We have reported that anthocyanins are associated with better body composition in children, but the associations with bone health have not been elucidated. We aimed to explore the association of anthocyanins with bone mineral content (BMC) and bone mineral density (BMD) at multiple sites in children. METHODS: In this cross-sectional study, 452 Chinese children aged 6-9 years were recruited. A validated 79-item food frequency questionnaire was used to collect dietary information. BMC and BMD at multiple sites (whole body; whole body excluding head, WBEH; limbs; arms; legs) were measured by dual-energy X-ray. RESULTS: Higher dietary intake of total anthocyanidins (per one standard deviation increase) was associated with a 1.28-13.6 g (1.31-1.60%, compared to median) higher BMC at all sites and a 3.61-6.96 mg (0.65-0.90%) higher BMD at the whole body, WBEH, and arm sites after controlling for a number of possible covariates. The results were similar and more pronounced for cyanidin, but not for delphinidin and peonidin. Higher dietary intake of cyanidin (per one standard deviation increase) was associated with a 1.33-15.4 g (1.48-1.68%) higher BMC at all sites and a 4.15-7.77 mg (0.66-1.00%) higher BMD at all sites except the legs. No statistically significant associations with BMC or BMD were found for dietary intake of delphinidin and peonidin. CONCLUSIONS: Higher dietary intake of total anthocyanidins and cyanidins were associated with higher BMC and BMD in Chinese children.

Structural, physicochemical and digestive properties of rice starch modified by preheating and pullulanase treatments.

The structural, physicochemical and digestive properties of rice starch modified by the combination of different temperature (60, 70, 80, 90 and 100 °C) preheating and pullulanase (PUL60, PUL70, PUL80, PUL90 and PUL100) treatments were investigated. The PUL60 treatment mainly modified the surface layer of starch granules, which increased the amylose content and damaged some ordered structures, resulting in slight decreases of gel strength and estimated glycemic index (eGI). With the increase of preheating temperature, PUL could act on more enzymatic sites to release a large amount of linear chains, reduce the ordered degree, and transform the A-type crystalline structure into B-type. The low molecule interaction strength between linear chains weakened the gel network structure, and some stable crystal structures formed by longer chains resisted the enzyme digestion. The gel strength and eGI value of PUL70 starch decreased significantly, and the properties of PUL80-100 starches tended to be stable, showing a further significant decrease of gel strength and a slight reduction of eGI value. Therefore, the preheating treatments at 60, 70 and 80 °C were suitable for the PUL modification of rice starch to obtain strong, medium and weak gel strength respectively, and the digestibility decreased with increasing preheating temperature.

Associations of serum concentrations of metal nutrients with postpartum anemia among pregnant Chinese women: A large retrospective cohort study.

Background and Aims: The association between serum concentrations of metal nutrients in pregnancy and postpartum anemia has not been widely studied. This study aimed to determine this association in a large retrospective cohort study. Methods: We included 14,829 Chinese women with singleton pregnancies. Serum concentrations of metals before 28 weeks of gestation, the occurrence of postpartum anemia and other potential covariates were obtained from their laboratory or medical records. Cox regression and restricted cubic spline regression models were used to explore the relationship between serum concentrations of metal nutrients in pregnancy and postpartum anemia. Results: After adjustment for covariates, higher concentrations of iron (Fe), magnesium (Mg) and zinc (Zn) and lower concentrations of copper (Cu) were associated with a lower risk of postpartum anemia. Compared with those whose serum concentrations of metal nutrients were in the bottom quintile (Q1), the hazard ratios (HRs) of those whose serum concentrations of metal nutrients were in the top quintile (Q5) were 0.57 (95% confidence interval (CI): 0.50, 0.64) for Fe, 0.67 (95% CI: 0.60, 0.76) for Mg, 0.82 (95% CI: 0.73, 0.93) for Zn, and 1.44 (95% CI: 1.28, 1.63) for Cu. L-shaped curve relationships were found between increasing concentrations of Fe, Mg, and Zn and incidence of postpartum anemia. Higher serum concentrations of Cu were associated with an increased risk of postpartum anemia. Serum concentrations of Fe in Q5 were associated with a lower risk of postpartum anemia when they coincided with serum concentrations of Mg in Q5, Zn in Q5, or Cu in Q1. Conclusion: Higher serum concentrations of Fe, Mg, and Zn, and lower serum concentrations of Cu were associated with a lower risk of postpartum anemia among pregnant women.

Understanding the texture and digestibility attributes of rice noodles supplemented with common vetch starch.

The effects of common vetch starch (CVS) substitution on rice noodle quality were investigated, aiming to improve their texture and reduce starch digestibility. The CVS had larger granule sizes, higher amylose content and more long branch chains compared with rice starch (RS). When the CVS substitution level was 20 %, the rice noodles had the best texture quality, as the mixtures with more total starch and amylose could form denser gel structures. Moreover, the starch chains were easier to rearrange to form double helix ordered structures, resulting in a slower digestion rate. With the further increase of CVS, the noodle structure weakened and the starch digestion rate increased. This was due to the formation of looser gel structures and less ordered structures as RS granules could be easily separated into different parts by large amount of CVS with larger granule sizes, and RS with more short chains tended to be cross-linked with RS during retrogradation. With increasing CVS substitution level, the estimated glycemic index (eGI) of rice noodles decreased and then tended to be stable. Therefore, appropriate CVS substitution could improve the texture quality of rice noodles and reduce the eGI value, and the best substitution level was 20 %.

Interaction of n-3 polyunsaturated fatty acids with host CD36 genetic variant for gut microbiome and blood lipids in human cohorts.

BACKGROUND & AIMS: Previous studies suggest an interaction of CD36 genetic variant rs1527483 with n-3 polyunsaturated fatty acids (PUFAs) to modulate blood lipids. However, successful replication is lacking and the role of gut microbiome remains unclear. Here, we aimed to replicate these gene-diet interactions on blood lipids and investigate their possible associations with gut microbiome. METHODS: We evaluated the n-3 PUFA-rs1527483 interaction on blood lipids in two population-based cohorts (n = 4,786). We profiled fecal microbiome and short-chain fatty acids among 1,368 participants. The associations between n-3 PUFAs and bacterial alpha-diversity, taxonomies and short-chain fatty acids by rs1527483 genotypes were analyzed using regression models. RESULTS: CD36 rs1527483-GG carriers responded better to high n-3 PUFA exposure; higher blood HDL-C (beta (95% CI): 0.05 (0.01, 0.08) mmol/L) and lower TG (log-transformed, beta (95% CI): -0.08 (-0.14, -0.02)) were observed among participants whose n-3 PUFA exposure ranked in the top quartile comparing with those in the bottom quartile. We identified docosahexaenoic acid (DHA) as the driven individual n-3 PUFA biomarker, which showed interaction with rs1527483. Among the rs1527483-GG carriers, but not other genotype groups, DHA exposure was positively associated with bacterial Faith's phylogenetic diversity, Observed OTUs, Shannon's diversity index, Dorea, Coriobacteriales Incertae Sedis spp, and fecal propionic acid levels. Another independent longitudinal cohort validated the DHA-rs1527483 interaction on gut microbiome. The identified microbial features were correlated with blood lipids, and the host biosynthesis and metabolism pathways of bile acids and aromatic amino acids. CONCLUSIONS: The present study found that higher n-3 PUFAs were associated with improved blood lipids and gut microbial features only among rs1527483-GG carriers. These findings highlight a potential role of gut microbiome to link the CD36 genetic variant, n-3 PUFAs and blood lipids, revealing a new research direction to interpret the gene-diet interaction for cardiometabolic health.

Expression of miR-4739 in Gastric cancer and its Relationship with Clinical Pathological Features of Patients.

Objective: To investigate the expression level of miR-4739 in gastric cancer (GC), analyze its diagnostic value in GC and the relationship with clinical pathological characteristics, and analyze its impact on the prognosis of patients. Methods: A total of 96 patients with GC who underwent radical gastrectomy in our hospital from March 2017 to June 2021 were selected. GC tissues from all patients were collected, and normal tissues adjacent to cancer were collected as controls. The expression level of miR-4739 in tissues was detected, the relationship between miR-4739 and different pathological features was analyzed, and the diagnostic value of miR-4739 in GC was analyzed. All patients were followed up after the operation, and the survival time of the patients was set as from the day of the first operation to 1 d when the patients died or the follow-up ended. Results: The relative expression level of miR-4739 in the GC tissue was (0.39 ± 0.06), lower than that in the paracancerous tissue (1.18 ± 0.19) (P < 0.05). The AUC of miR-4739 in the diagnosis of GC was 0.705. When the Youden index was 0.320 and the optimal cutoff value was 0.37, the sensitivity was 95.30% and the specificity was 36.70%. The expression level of miR-4739 in our patient was related to the differentiation degree, lymph node metastasis, tumor diameter, and TNM stage (P < 0.05). During the follow-up period, 26 of 96 patients died, and the survival rate was 72.92% (26/96). The median survival time was 29 months in the miR-4739 LE group, which was shorter than 39 months in the miR-4739 HE group (P < 0.05). Univariate analysis showed that age, degree of differentiation, lymph node metastasis, tumor diameter, TNM staging, and miR-4739 expression were all related to the prognosis of the patient (P < 0.05). Multivariate analysis showed that differentiation degree, lymph node metastasis, tumor diameter, TNM staging, and miR-4739 expression were all independent factors affecting the prognosis of the patients (P < 0.05). Conclusion: The expression of miR-4739 in GC tissue was down-regulated, and its level was related to the degree of differentiation, lymph node metastasis, tumor diameter, and TNM stage. The expression level of miR-4739 has certain diagnostic value for patients with GC, and the prognosis of patients in LE group was worse than that in HE group.

Incidence and management of CAR-T neurotoxicity in patients with multiple myeloma treated with ciltacabtagene autoleucel in CARTITUDE studies.

Chimeric antigen receptor (CAR) T-cell therapies are highly effective for multiple myeloma (MM) but their impressive efficacy is associated with treatment-related neurotoxicities in some patients. In CARTITUDE-1, 5% of patients with MM reported movement and neurocognitive treatment-emergent adverse events (MNTs) with ciltacabtagene autoleucel (cilta-cel), a B-cell maturation antigen-targeted CAR T-cell therapy. We assessed the associated factors for MNTs in CARTITUDE-1. Based on common features, patients who experienced MNTs were characterized by the presence of a combination of at least two variables: high tumor burden, grade ≥2 cytokine release syndrome (CRS) or any grade immune effector cell-associated neurotoxicity syndrome (ICANS) after cilta-cel infusion, and high CAR T-cell expansion/persistence. Strategies were implemented across the cilta-cel development program to monitor and manage patients with MNTs, including enhanced bridging therapy to reduce baseline tumor burden, early aggressive treatment of CRS and ICANS, handwriting assessments for early symptom detection, and extended monitoring/reporting time for neurotoxicity beyond 100 days post-infusion. After successful implementation of these strategies, the incidence of MNTs was reduced from 5% to <1% across the cilta-cel program, supporting its favorable benefit-risk profile for treatment of MM.

Associations between thyroid function and gestational diabetes mellitus in Chinese pregnant women: a retrospective cohort study.

BACKGROUND: Thyroid function is known to be closely linked with type 2 diabetes, but data on the association between thyroid function and gestational diabetes mellitus (GDM) are inconsistent. METHODS: A total of 2849 pregnant women were included in this retrospective study. Serum concentrations of thyroid indicators (free tetraiodothyronine, FT4; thyroid-stimulating hormone, TSH; and thyroid peroxidase antibody, TPO Ab) were obtained from a clinical laboratory. The presence of GDM were drawn from medical records. The clinical subtypes of thyroid function (euthyroidism, subclinical hypothyroidism, hyperthyroidism, and isolated hypothyroxinemia) were categorized according to the thresholds of the 2.5th/97.5th and 10th/90th percentiles of TSH and FT4 concentrations. A concentration of > 34 IU/L was defined as indicating TPO Ab-positivity. RESULTS: Two hundred and thirty-five (8.25%) of the 2849 women were TPO Ab-positive. Higher serum concentrations of FT4 (top vs. bottom tertiles) was found to be negatively associated with the risk of GDM. The corresponding odds (OR) values (top tertile vs. bottom tertile) were 0.71 [95% confidence interval (CI): 0.54, 0.93]. No significant associations were observed between the extremely 2.5th/97.5th or 10th/90th percentiles of FT4 concentration, TSH concentration, thyroid function subtypes (vs. euthyroidism), TPO Ab-positivity (vs. -negativity), and the GDM risk. The corresponding results remained similar when TPO Ab-positive subjects were excluded. CONCLUSIONS: A negative association with the risk of GDM was observed for the highest FT4 concentrations tertile. No significant associations were found between the TSH concentration, thyroid function subtypes, TPO Ab positivity, and the GDM risk.

Anti-drug Antibody Validation Testing and Reporting Harmonization.

Evolving immunogenicity assay performance expectations and a lack of harmonized anti-drug antibody validation testing and reporting tools have resulted in significant time spent by health authorities and sponsors on resolving filing queries. Following debate at the American Association of Pharmaceutical Sciences National Biotechnology Conference, a group was formed to address these gaps. Over the last 3 years, 44 members from 29 organizations (including 5 members from Europe and 10 members from FDA) discussed gaps in understanding immunogenicity assay requirements and have developed harmonization tools for use by industry scientists to facilitate filings to health authorities. Herein, this team provides testing and reporting strategies and tools for the following assessments: (1) pre-study validation cut point; (2) in-study cut points, including procedures for applying cut points to mixed populations; (3) system suitability control criteria for in-study plate acceptance; (4) assay sensitivity, including the selection of an appropriate low positive control; (5) specificity, including drug and target tolerance; (6) sample stability that reflects sample storage and handling conditions; (7) assay selectivity to matrix components, including hemolytic, lipemic, and disease state matrices; (8) domain specificity for multi-domain therapeutics; (9) and minimum required dilution and extraction-based sample processing for titer reporting.

Gut microbiota, inflammation, and molecular signatures of host response to infection.

Gut microbial dysbiosis has been linked to many noncommunicable diseases. However, little is known about specific gut microbiota composition and its correlated metabolites associated with molecular signatures underlying host response to infection. Here, we describe the construction of a proteomic risk score based on 20 blood proteomic biomarkers, which have recently been identified as molecular signatures predicting the progression of the COVID-19. We demonstrate that in our cohort of 990 healthy individuals without infection, this proteomic risk score is positively associated with proinflammatory cytokines mainly among older, but not younger, individuals. We further discover that a core set of gut microbiota can accurately predict the above proteomic biomarkers among 301 individuals using a machine learning model and that these gut microbiota features are highly correlated with proinflammatory cytokines in another independent set of 366 individuals. Fecal metabolomics analysis suggests potential amino acid-related pathways linking gut microbiota to host metabolism and inflammation. Overall, our multi-omics analyses suggest that gut microbiota composition and function are closely related to inflammation and molecular signatures of host response to infection among healthy individuals. These results may provide novel insights into the cross-talk between gut microbiota and host immune system.

The Association of Gut Microbiota With Osteoporosis Is Mediated by Amino Acid Metabolism: Multiomics in a Large Cohort.

CONTEXT: Several small studies have suggested that the gut microbiome might influence osteoporosis, but there is little evidence from human metabolomics studies to explain this association. OBJECTIVE: This study examined the association of gut microbiome dysbiosis with osteoporosis and explored the potential pathways through which this association occurs using fecal and serum metabolomics. METHODS: We analyzed the composition of the gut microbiota by 16S rRNA profiling and bone mineral density using dual-energy X-ray absorptiometry in 1776 community-based adults. Targeted metabolomics in feces (15 categories) and serum (12 categories) were further analyzed in 971 participants using ultra-high-performance liquid chromatography coupled to tandem mass spectrometry. RESULTS: This study showed that osteoporosis was related to the beta diversity, taxonomy, and functional composition of the gut microbiota. The relative abundance of Actinobacillus, Blautia, Oscillospira, Bacteroides, and Phascolarctobacterium was positively associated with osteoporosis. However, Veillonellaceae other, Collinsella, and Ruminococcaceae other were inversely associated with the presence of osteoporosis. The association between microbiota biomarkers and osteoporosis was related to levels of peptidases and transcription machinery in microbial function. Fecal and serum metabolomics analyses suggested that tyrosine and tryptophan metabolism and valine, leucine, and isoleucine degradation were significantly linked to the identified microbiota biomarkers and to osteoporosis, respectively. CONCLUSION: This large population-based study provided robust evidence connecting gut dysbiosis, fecal metabolomics, and serum metabolomics with osteoporosis. Our results suggest that gut dysbiosis and amino acid metabolism could be targets for intervention in osteoporosis.

Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b/2 open-label study.

BACKGROUND: CARTITUDE-1 aimed to assess the safety and clinical activity of ciltacabtagene autoleucel (cilta-cel), a chimeric antigen receptor T-cell therapy with two B-cell maturation antigen-targeting single-domain antibodies, in patients with relapsed or refractory multiple myeloma with poor prognosis. METHODS: This single-arm, open-label, phase 1b/2 study done at 16 centres in the USA enrolled patients aged 18 years or older with a diagnosis of multiple myeloma and an Eastern Cooperative Oncology Group performance status score of 0 or 1, who received 3 or more previous lines of therapy or were double-refractory to a proteasome inhibitor and an immunomodulatory drug, and had received a proteasome inhibitor, immunomodulatory drug, and anti-CD38 antibody. A single cilta-cel infusion (target dose 0·75 × 106 CAR-positive viable T cells per kg) was administered 5-7 days after start of lymphodepletion. The primary endpoints were safety and confirmation of the recommended phase 2 dose (phase 1b), and overall response rate (phase 2) in all patients who received treatment. Key secondary endpoints were duration of response and progression-free survival. This trial is registered with ClinicalTrials.gov, NCT03548207. FINDINGS: Between July 16, 2018, and Oct 7, 2019, 113 patients were enrolled. 97 patients (29 in phase 1b and 68 in phase 2) received a cilta-cel infusion at the recommended phase 2 dose of 0·75 × 106 CAR-positive viable T cells per kg. As of the Sept 1, 2020 clinical cutoff, median follow-up was 12·4 months (IQR 10·6-15·2). 97 patients with a median of six previous therapies received cilta-cel. Overall response rate was 97% (95% CI 91·2-99·4; 94 of 97 patients); 65 (67%) achieved stringent complete response; time to first response was 1 month (IQR 0·9-1·0). Responses deepened over time. Median duration of response was not reached (95% CI 15·9-not estimable), neither was progression-free survival (16·8-not estimable). The 12-month progression-free rate was 77% (95% CI 66·0-84·3) and overall survival rate was 89% (80·2-93·5). Haematological adverse events were common; grade 3-4 haematological adverse events were neutropenia (92 [95%] of 97 patients), anaemia (66 [68%]), leukopenia (59 [61%]), thrombocytopenia (58 [60%]), and lymphopenia (48 [50%]). Cytokine release syndrome occurred in 92 (95%) of 97 patients (4% were grade 3 or 4); with median time to onset of 7·0 days (IQR 5-8) and median duration of 4·0 days (IQR 3-6). Cytokine release syndrome resolved in all except one with grade 5 cytokine release syndrome and haemophagocytic lymphohistiocytosis. CAR T-cell neurotoxicity occurred in 20 (21%) patients (9% were grade 3 or 4). 14 deaths occurred in the study; six due to treatment-related adverse events, five due to progressive disease, and three due to treatment-unrelated adverse events. INTERPRETATION: A single cilta-cel infusion at the target dose of 0·75 × 106 CAR-positive viable T cells per kg led to early, deep, and durable responses in heavily pretreated patients with multiple myeloma with a manageable safety profile. The data from this study formed the basis for recent regulatory submissions. FUNDING: Janssen Research & Development and Legend Biotech.

Effects of damaged starch on glutinous rice flour properties and sweet dumpling qualities.

This study focused on exploring the effects of damaged starch on glutinous rice flour properties and sweet dumpling qualities. Glutinous rice flours with different damaged starch contents (2-8%) and the same particle size were prepared through sifting and blending of semidry-milled and dry-milled rice flour. The increase of damaged starch content led to an increase in elastic modulus (G'), viscous modulus (G″) and agglomeration of starch granules, and a decrease in peak viscosity, breakdown value and enthalpy change (ΔH). Among all the samples, the rice flour batters with damaged starch content 3% and 4% were more stable and structured, and rice flours with damaged starch content 2% and 3% showed better pasting properties. As for the sweet dumpling qualities, compact structure, weak water mobility, less water loss, slight cracking and desirable cooking and texture properties were observed in the sweet dumplings made from rice flour with damaged starch content of less than 5%. All the results demonstrated that glutinous rice flour with damaged starch content of less than 5% had good flour properties and was suitable for the production of sweet dumplings.

Volumetric absorptive microsampling (VAMS®) in therapeutic protein quantification by LC-MS/MS: Investigation of anticoagulant impact on assay performance and recommendations for best practices in method development.

Microsampling techniques have been employed as an alternative to traditional serum/plasma sampling because of their inherently proven and desirable advantages across the pharmaceutical industry. These include reduced animal usage in pre-clinical studies, as well as, permitting the collection of samples that would otherwise be inaccessible in clinical studies. The application of volumetric absorptive microsampling (VAMS®) technology, a second-generation dried microsampling method, coupled with LC-MS, has been extensively explored for small molecule drugs at various drug development stages. However, the potential of using VAMS technology and LC-MS analysis for biological therapeutic development has yet to be well-established. In this work, we describe the method development, validation, and a proof-of-concept non-human primate study of a LC-MS/MS method for VAMS utilized to obtain pharmacokinetic (PK) data for a therapeutic monoclonal antibody. A good correlation between VAMS data and data from conventional serum samples was established in rhesus monkeys and indicated the possibility of using of this novel sampling technology in clinical studies. However, during the initial clinical study, a significant difference in internal standard (IS) response between the patient fingerstick samples and the standard/QC samples was observed, which posed a question on the accuracy of the clinical results. A comprehensive investigation confirmed that the EDTA anticoagulant used in the standard/QC samples was the root cause of the observed anomalous IS responses. Special considerations and corresponding best practices during method development and validation are proposed to ensure early detection of potential issues and appropriate implementation of VAMS technology in clinical studies in the future.

Dietary Proteins Alter Fermentation Characteristics of Human Gut Microbiota In Vitro.

The objective of this study was to evaluate the fermentation characteristics of proteins from diverse sources by human gut microbiota. Cereal proteins (rice and oat), red meat proteins (pork and beef), chicken protein and casein were selected as the substrates for simulated gastrointestinal digestion (SGID), and human faecal samples were collected from healthy donors as the inoculum of fermentation. In this study, we further analyzed the correlations of amino acids (AA) compositions, fermentation productions and gut microbiota. As the results, the animal protein groups had higher degree of hydrolysis (DH) after digestion and higher levels of ammonia nitrogen (NH3-N) after fermentation than cereal proteins. The pH value of fermentation liquid declined as proteins were added during fermentation. Cereal protein groups promoted the gut microbiota to produce more short chain fatty acids (SCFAs) with the high proportion of acetate, propionate and butyrate by lowering the pH than red meat proteins. The abundance of Firmicutes at phylum level in cereal protein groups was lower than red meat proteins after fermentation. The cereal protein groups enhanced the growth of Bacteroides spp. and Bifidobacterium spp. while red meat proteins stimulated the growth of Peptoclostridium spp.. Taken together, our research implies that cereal proteins have better fermentation characters than red meat proteins.

Effects of Lactobacillus plantarum Inoculum on the Fermentation Rate and Rice Noodle Quality.

To accelerate the fermentation rate and reduce the adverse effects of undesirable microorganism contamination on rice noodle quality, the pure inoculum fermentation method was used to produce fermented rice noodles. The results indicated that the pure inoculum fermented rice slurry required 10 h to reach a stable pH value. While, the pH value of the natural, pure and natural inoculum fermented rice slurries required 54, 18 and 20 h to stabilize, respectively. Free amino acids and lactic acid concentrations of the pure inoculum fermented rice slurry were higher than those of the natural and natural inoculum fermented rice slurries. The pure inoculum fermentation modified the proximate composition and lowered the pasting viscosities of the rice flour. The texture, cooking and eating qualities of the pure inoculum fermented rice noodles were similar to those of the natural fermented ones. In addition, the pure inoculum fermented rice noodles had higher relative contents of aldehydes than other fermented rice noodles and thus had a better flavor. Therefore, pure inoculum fermentation accelerated the fermentation rate and improved the rice noodle flavor while maintaining the texture, cooking and eating qualities of the rice noodles.