An In Vitro Comparison of the Digestibility and Gastrointestinal Fate of Scallops and Plant-Based Scallop Analogs

Concerns exist regarding the negative environmental impact and health risks associated with ocean fishing and aquaculture, such as stock depletion, pollution, biodiversity loss, and toxin presence. To address these concerns, plant-based seafood analogs are being developed. Our previous study successfully created plant-based scallop analogs using pea proteins and citrus pectin, resembling real scallops in appearance and texture. This study focuses on comparing the digestive fate of these analogs to real scallops, as it can impact their nutritional properties. Using an in vitro digestion model (INFOGEST), we simulated oral, gastric, and small intestinal conditions. The analysis revealed differences in the microstructure, physicochemical properties, and protein digestibility between the plant-based scallops and real scallops. The particle size and charge followed the following similar trends for both types of scallops: the particle size decreased from the mouth to the stomach to the small intestine; the particles were negative in the mouth, positive in the stomach, and negative in the small intestine. The protein digestibility of the plant-based scallops was considerably lower than that of real scallops. For instance, around 18.8% and 61.4% of protein was digested in the stomach and small intestine phases for the real scallop (80.2% total digestion), whereas around 8.7% and 47.7% of the protein was digested for the plant-based scallop (56.4% total digestion). The lower digestibility of the plant-based scallops may have been due to differences in the protein structure, the presence of dietary fibers (pectin), or antinutritional factors in the plant proteins. These findings are crucial for developing more sustainable next-generation plant-based seafood analogs

PLM-ARG: antibiotic resistance gene identification using a pretrained protein language model

Motivation: Antibiotic resistance presents a formidable global challenge to public health and the environment. While considerable endeavors have been dedicated to identify antibiotic resistance genes (ARGs) for assessing the threat of antibiotic resistance, recent extensive investigations using metagenomic and metatranscriptomic approaches have unveiled a noteworthy concern. A significant fraction of proteins defies annotation through conventional sequence similarity-based methods, an issue that extends to ARGs, potentially leading to their under-recognition due to dissimilarities at the sequence level. Results: Herein, we proposed an Artificial Intelligence-powered ARG identification framework using a pretrained large protein language model, enabling ARG identification and resistance category classification simultaneously. The proposed PLM-ARG was developed based on the most comprehensive ARG and related resistance category information (>28K ARGs and associated 29 resistance categories), yielding Matthew’s correlation coefficients (MCCs) of 0.983 ± 0.001 by using a 5-fold cross-validation strategy. Furthermore, the PLM-ARG model was verified using an independent validation set and achieved an MCC of 0.838, outperforming other publicly available ARG prediction tools with an improvement range of 51.8%–107.9%. Moreover, the utility of the proposed PLM-ARG model was demonstrated by annotating resistance in the UniProt database and evaluating the impact of ARGs on the Earth's environmental microbiota. Availability and implementation: PLM-ARG is available for academic purposes at https://github.com/Junwu302/PLM-ARG, and a user-friendly webserver (http://www.unimd.org/PLM-ARG) is also provided

Exposure time relevance of response to nitrite exposure: Insight from transcriptional responses of immune and antioxidant defense in the crayfish, Procambarus clarkii

Abstract(#br)To understand the toxic effects of nitrite exposure on crayfish, expression of genes involved in the immune system, the antioxidant defense, and the heat shock protein 70 (HSP70) was measured after 12, 24, and 48 h of different nitrite concentrations exposure in the hepatopancreas and hemocytes of Procambarus clarkii . Nitrite exposure up-regulated mRNA levels of cytoplasmic Mn superoxide dismutase (cMn-SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione-S-transferase (GST), after 24 h nitrite exposure. At 48 h, nitrite exposure decreased the mRNA levels of mitochondrial MnSOD (mMn-SOD), CAT, and GPx. High concentrations of nitrite at 48 h of exposure decreased expression of β-1,3-glucan-bingding protein in the hepatopancreas, and lysozyme expression in hemocytes. Nitrite exposure caused little effect on the heat shock protein 70 (HSP70) in hemocytes. Through overall clustering analysis, we found that 24 h of nitrite exposure caused stronger transcriptional responses. Our study indicated that the response of P. clarkii to acute nitrite exposure was exposure time-dependent. These results will help to understand the dynamic response pattern of crustaceans to nitrite pollution, and improve our understanding of the toxicological mechanisms of nitrite in crustaceans

A Left Ventricular Mechanical Dyssynchrony-Based Nomogram for Predicting Major Adverse Cardiac Events Risk in Patients With Ischemia and No Obstructive Coronary Artery Disease.

Background The risk stratification of patients with ischemia and no obstructive coronary artery disease (INOCA) remains suboptimal. This study aims to establish a left ventricular mechanical dyssynchrony (LVMD)-based nomogram to improve the present situation. Methods Patients with suspected coronary artery disease (CAD) were retrospectively enrolled and divided into three groups: normal (stenosis 4, summed difference score ≥2), and obstructive CAD (stenosis ≥50%). LVMD was defined by ROC analysis. INOCA group were followed up for the occurrence of major adverse cardiac events (MACEs: cardiovascular death, non-fatal myocardial infarction, revascularization, stroke, heart failure, and hospitalization for unstable angina). Nomogram was established using multivariate Cox regression analysis. Results Among 334 patients (118 [35.3%] INOCA), LVMD parameters were significantly higher in INOCA group versus normal group but they did not differ between obstructive CAD groups. In INOCA group, 27 (22.9%) MACEs occurred during a 26-month median follow-up. Proportion of LVMD was significantly higher with MACEs under both stress (63.0% vs. 22.0%, P < 0.001) and rest (51.9% vs. 20.9%, P = 0.002). Kaplan-Meier analysis revealed significantly higher rate of MACEs (stress log-rank: P = 0.002; rest log-rank: P < 0.001) in LVMD patients. Multivariate Cox regression analysis showed that stress LVMD (HR: 3.82; 95% CI: 1.30-11.20; P = 0.015) was an independent predictor of MACEs. The internal bootstrap resampling approach indicates that the C-index of nomogram was 0.80 (95% CI: 0.71-0.89) and the AUC values for 1 and 3 years of risk prediction were 0.68 (95% CI: 0.46-0.89) and 0.84 (95% CI: 0.72-0.95), respectively. Conclusion LVMD-based nomogram might provide incremental prognostic value and improve the risk stratification in INOCA patients

FT4/FT3 ratio: A novel biomarker predicts coronary microvascular dysfunction (CMD) in euthyroid INOCA patients.

Background Ischemia and no obstructive coronary artery disease (INOCA) patients who presented coronary microvascular dysfunction (CMD) demonstrate a poor prognosis, yet the risk factors for CMD remain unclear. Subtle changes in thyroid hormone levels within the normal range, especially the free thyroxine (FT4)/free triiodothyronine (FT3) ratio, have been shown to regulate the cardiovascular system. This prospective study investigated the correlation between FT4/FT3 ratio and CMD in euthyroid patients with INOCA. Methods This prospective study (www.chictr.org.cn/, ChiCTR2000037112) recruited patients with myocardial ischemia symptoms who underwent both coronary angiography (CAG) and myocardial perfusion imaging (MPI) with dynamic single-photon emission computed tomography (D-SPECT). INOCA was defined as coronary stenosis< 50% and CMD was defined as coronary flow reserve (CFR)<2.5. All patients were excluded from abnormal thyroid function and thyroid disease history. Results Among 71 INOCA patients (15 [21.1%] CMD), FT4 and FT4/FT3 ratio in CMD group were significantly higher and both showed significantly moderate correlation with CFR (r=-0.25, p=0.03; r=-0.34, p=0.003, respectively). The ROC curve revealed that FT4/FT3 ratio had the highest efficacy for predicting CMD with an optimized cutoff value>3.39 (AUC 0.78, p<0.001, sensitivity, 80.0%; specificity, 71.4%). Multivariate logistic regression showed that FT4/FT3 ratio was an independent predictor of CMD (OR 7.62, 95% CI 1.12-51.89, p=0.038, P for trend=0.006). Conclusion In euthyroid INOCA patients, increased FT4/FT3 ratio levels are associated with the occurrence of CMD, presenting a novel biomarker for improving the risk stratification

Human perivascular stem cells prevent bone graft resorption in osteoporotic contexts by inhibiting osteoclast formation

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NGF-p75 signaling coordinates skeletal cell migration during bone repair

: Bone regeneration following injury is initiated by inflammatory signals and occurs in association with infiltration by sensory nerve fibers. Together, these events are believed to coordinate angiogenesis and tissue reprogramming, but the mechanism of coupling immune signals to reinnervation and osteogenesis is unknown. Here, we found that nerve growth factor (NGF) is expressed following cranial bone injury and signals via p75 in resident mesenchymal osteogenic precursors to affect their migration into the damaged tissue. Mice lacking Ngf in myeloid cells demonstrated reduced migration of osteogenic precursors to the injury site with consequently delayed bone healing. These features were phenocopied by mice lacking p75 in Pdgfra+ osteoblast precursors. Single-cell transcriptomics identified mesenchymal subpopulations with potential roles in cell migration and immune response, altered in the context of p75 deletion. Together, these results identify the role of p75 signaling pathway in coordinating skeletal cell migration during early bone repair

Systemic DKK1 neutralization enhances human adipose-derived stem cell mediated bone repair

: Progenitor cells from adipose tissue are able to induce bone repair; however, inconsistent or unreliable efficacy has been reported across preclinical and clinical studies. Soluble inhibitory factors, such as the secreted Wnt signaling antagonists Dickkopf-1 (DKK1), are expressed to variable degrees in human adipose-derived stem cells (ASCs), and may represent a targetable "molecular brake" on ASC mediated bone repair. Here, anti-DKK1 neutralizing antibodies were observed to increase the osteogenic differentiation of human ASCs in vitro, accompanied by increased canonical Wnt signaling. Human ASCs were next engrafted into a femoral segmental bone defect in NOD-Scid mice, with animals subsequently treated with systemic anti-DKK1 or isotype control during the repair process. Human ASCs alone induced significant but modest bone repair. However, systemic anti-DKK1 induced an increase in human ASC engraftment and survival, an increase in vascular ingrowth, and ultimately improved bone repair outcomes. In summary, anti-DKK1 can be used as a method to augment cell-mediated bone regeneration, and could be particularly valuable in the contexts of impaired bone healing such as osteoporotic bone repair

Epidemiology of birth defects based on a birth defects surveillance system in southwestern China and the associated risk factors

BackgroundBirth defects (BDs) are associated with many potential risk factors, and its causes are complex.ObjectivesThis study aimed to explore the epidemiological characteristics of BDs in Guangxi of China and the associated risk factors of BDs.MethodsBDs data of perinatal infants (PIs) were obtained from the Guangxi birth defects monitoring network between 2016 and 2020. Univariate Poisson regression was used to calculate the prevalence-rate ratios (PRR) to explore the changing trends of BDs prevalence by year and the correlation between the regarding of characteristics of BDs (including infant gender, maternal age, and quarter) and BDs. Clinical characteristics of PIs with BDs and general characteristics of their mothers were documented, and Spearman correlation analysis was used to explore the potential associated risk factors of BDs.ResultsBetween 2016 and 2020, 44,146 PIs with BDs were monitored, with an overall BDs prevalence of 121.71 (95% CI: 120.58–122.84) per 10,000 PIs, showing a significant increase trend (PRR = 1.116, 95% CI: 1.108–1.123), especially the prevalence of congenital heart defects (CHDs) that most significantly increased (PRR = 1.300, 95% CI: 1.283–1.318). The 10 most common BDs were CHDs, polydactyly, congenital talipes equinovarus, other malformation of external ear, syndactyly, hypospadias, cleft lip with cleft palate, cleft lip, hemoglobin Bart's hydrops fetalis syndrome (BHFS), and congenital atresia of the rectum and anus. BDs were positively correlated with pregnant women's age (R = 0.732, P &lt; 0.01) and education level (R = 0.586, P &lt; 0.05) and having pre-gestational diabetes mellitus (PGDM)/gestational diabetes mellitus (GDM) (R = 0.711, P &lt; 0.01), while when the pregnant women had a family history of a dead fetus (R = −0.536, P &lt; 0.05) and a birth of a fetus with BDs (R = −0.528, P &lt; 0.05) were negatively correlated with BDs.ConclusionA significant increase in the prevalence of BDs was detected between 2016 and 2020 in Guangxi, especially the prevalence of CHDs that most significantly increased. Older maternal age, higher maternal education level, and having PGDM before pregnancy or GDM in early pregnancy were the risk factors for BDs