Not all soil carbon is created equal: Labile and stable pools under nitrogen input.

Anthropogenic activities have raised nitrogen (N) input worldwide with profound implications for soil carbon (C) cycling in ecosystems. The specific impacts of N input on soil organic matter (SOM) pools differing in microbial availability remain debatable. For the first time, we used a much-improved approach by effectively combining the 13C natural abundance in SOM with 21 years of C3-C4 vegetation conversion and long-term incubation. This allows to distinguish the impact of N input on SOM pools with various turnover times. We found that N input reduced the mineralization of all SOM pools, with labile pools having greater sensitivity to N than stable ones. The suppression in SOM mineralization was notably higher in the very labile pool (18%-52%) than the labile and stable (11%-47%) and the very stable pool (3%-21%) compared to that in the unfertilized control soil. The very labile C pool made a strong contribution (up to 60%) to total CO2 release and also contributed to 74%-96% of suppressed CO2 with N input. This suppression of SOM mineralization by N was initially attributed to the decreased microbial biomass and soil functions. Over the long-term, the shift in bacterial community toward Proteobacteria and reduction in functional genes for labile C degradation were the primary drivers. In conclusion, the higher the availability of the SOM pools, the stronger the suppression of their mineralization by N input. Labile SOM pools are highly sensitive to N availability and may hold a greater potential for C sequestration under N input at global scale.

Protocol for a feasibility randomized controlled trial of gentle yoga in older patients discharged from phase II cardiac rehabilitation.

Background: Physical activity (PA) is essential following an acute cardiac event. Cardiac rehabilitation (CR) is commonly prescribed, and PA after CR is recommended. Because of age-related changes in functional ability and multi-comorbidity, many older cardiac patients struggle to continue performing PA at home after CR. Depressive symptoms and anxiety are prevalent in cardiac patients and associated with poor self-care, including lack of daily PA. Yoga has been demonstrated to improve psychological and physical health outcomes in cardiac patients, but it is unknown whether yoga, modified for older CR patients - Gentle Yoga - is beneficial in managing psychological distress and maintaining PA following phase II CR. Our specific aims are to:1) determine the feasibility and acceptability of a modified gentle yoga intervention delivered via video conferencing for older cardiac patients; 2) compare, at 3-month follow-up, the effects and determine effect sizes of a gentle yoga intervention versus control on psychological health and physical health. Methods: We are conducting a 2-group (intervention versus control) randomized controlled pilot study. The intervention is a 12-week gentle yoga program delivered via video conference. Short-term effects will be evaluated at 3-month. Conclusion: This study is designed to be suited for older cardiac patients who would not have access to supervised PA opportunities after facility-based CR to enhance PA. This study will provide data about the feasibility and acceptability of the protocol for older cardiac patients and will offer effect sizes to determine sample size for a fully powered randomized controlled trial.

Nanopore sequencing of forensic short tandem repeats using QNome of Qitan Technology.

Devices of nanopore sequencing can be highly portable and of low cost. Thus, nanopore sequencing is promising in in-field forensic applications. Previous investigations have demonstrated that nanopore sequencing is feasible for genotyping forensic short tandem repeats (STRs) by using sequencers of Oxford Nanopore Technologies. Recently, Qitan Technology launched a new portable nanopore sequencer and became the second supplier in the world. Here, for the first time, we assess the QNome (QNome-3841) for its accuracy in nanopore sequencing of STRs and compare with MinION (MinION Mk1B). We profile 54 STRs of 21 unrelated individuals and 2800M standard DNA. The overall accuracy for diploid STRs and haploid STRs were 53.5% (378 of 706) and 82.7% (134 of 162), respectively, by using QNome. The accuracies were remarkably lower than those of MinION (diploid STRs, 84.5%; haploid, 90.7%), with a similar amount of sequencing data and identical bioinformatics analysis. Although it was not reliable for diploid STRs typing by using QNome, the haploid STRs were consistently correctly typed. The majority of errors (58.8%) in QNome-based STR typing were one-repeat deviations of repeat units in the error from true allele, related with homopolymers in repeats of STRs.

Adapting the serious illness conversation guide for unhoused older adults: a rapid qualitative study.

BACKGROUND: Older adults experiencing homelessness (OAEH) age quickly and die earlier than their housed counterparts. Illness-related decisions are best guided by patients' values, but healthcare and homelessness service providers need support in facilitating these discussions. The Serious Illness Conversation Guide (SICG) is a communication tool to guide discussions but has not yet been adapted for OAEH. METHODS: We aimed to adapt the SICG for use with OAEH by nurses, social workers, and other homelessness service providers. We conducted semi-structured interviews with homelessness service providers and cognitive interviews with OAEH using the SICG. Service providers included nurses, social workers, or others working in homeless settings. OAEH were at least 50 years old and diagnosed with a serious illness. Interviews were conducted and audio recorded in shelters, transitional housing, a hospital, public spaces, and over Zoom. The research team reviewed transcripts, identifying common themes across transcripts and applying analytic notetaking. We summarized transcripts from each participant group, applying rapid qualitative analysis. For OAEH, data that referenced proposed adaptations or feedback about the SICG tool were grouped into two domains: "SICG interpretation" and "SICG feedback". For providers, we used domains from the Toolkit of Adaptation Approaches: "collaborative working", "team", "endorsement", "materials", "messages", and "delivery". Summaries were grouped into matrices to help visualize themes to inform adaptations. The adapted guide was then reviewed by expert palliative care clinicians for further refinement. RESULTS: The final sample included 11 OAEH (45% Black, 61 ± 7 years old) and 10 providers (80% White, 8.9 ± years practice). Adaptation themes included changing words and phrases to (1) increase transparency about the purpose of the conversation, (2) promote OAEH autonomy and empowerment, (3) align with nurses' and social workers' scope of practice regarding facilitating diagnostic and prognostic awareness, and (4) be sensitive to the realities of fragmented healthcare. Responses also revealed training and implementation considerations. CONCLUSIONS: The adapted SICG is a promising clinical tool to aid in the delivery of serious illness conversations with OAEH. Future research should use this updated guide for implementation planning. Additional adaptations may be dependent on specific settings where the SICG will be delivered.

Recent advances in C(sp3)-N bond formation via metallaphoto-redox catalysis.

The C(sp3)-N bond is ubiquitous in natural products, pharmaceuticals, biologically active molecules and functional materials. Consequently, the development of practical and efficient methods for C(sp3)-N bond formation has attracted more and more attention. Compared to the conventional ionic pathway-based thermal methods, photochemical processes that proceed through radical mechanisms by merging photoredox and transition-metal catalyses have emerged as powerful and alternative tools for C(sp3)-N bond formation. In this review, recent advances in the burgeoning field of C(sp3)-N bond formation via metallaphotoredox catalysis have been highlighted. The contents of this review are categorized according to the transition metals used (copper, nickel, cobalt, palladium, and iron) together with photocatalysis. Emphasis is placed on methodology achievements and mechanistic insight, aiming to inspire chemists to invent more efficient radical-involved C(sp3)-N bond-forming reactions.

The influence of sleep disorders on perioperative neurocognitive disorders among the elderly: A narrative review.

This review comprehensively assesses the epidemiology, interaction, and impact on patient outcomes of perioperative sleep disorders (SD) and perioperative neurocognitive disorders (PND) in the elderly. The incidence of SD and PND during the perioperative period in older adults is alarmingly high, with SD significantly contributing to the occurrence of postoperative delirium. However, the clinical evidence linking SD to PND remains insufficient, despite substantial preclinical data. Therefore, this study focuses on the underlying mechanisms between SD and PND, underscoring that potential mechanisms driving SD-induced PND include uncontrolled central nervous inflammation, blood-brain barrier disruption, circadian rhythm disturbances, glial cell dysfunction, neuronal and synaptic abnormalities, impaired central metabolic waste clearance, gut microbiome dysbiosis, hippocampal oxidative stress, and altered brain network connectivity. Additionally, the review also evaluates the effectiveness of various sleep interventions, both pharmacological and nonpharmacological, in mitigating PND. Strategies such as earplugs, eye masks, restoring circadian rhythms, physical exercise, noninvasive brain stimulation, dexmedetomidine, and melatonin receptor agonists have shown efficacy in reducing PND incidence. The impact of other sleep-improvement drugs (e.g., orexin receptor antagonists) and methods (e.g., cognitive-behavioral therapy for insomnia) on PND is still unclear. However, certain drugs used for treating SD (e.g., antidepressants and first-generation antihistamines) may potentially aggravate PND. By providing valuable insights and references, this review aimed to enhance the understanding and management of PND in older adults based on SD.

Surface PD-1 expression in T cells is suppressed by HNRNPK through an exonic splicing silencer on exon 3.

OBJECTIVE: Immunotherapy targeting programmed cell death 1 (PDCD1 or PD-1) and its ligands has shown remarkable promise and the regulation mechanism of PD-1 expression has received arising attention in recent years. PDCD1 exon 3 encodes the transmembrane domain and the deletion of exon 3 produces a soluble protein isoform of PD-1 (sPD-1), which can enhance immune response by competing with full-length PD-1 protein (flPD-1 or surface PD-1) on T cell surface. However, the mechanism of PDCD1 exon 3 skipping is unclear. METHODS: The online SpliceAid program and minigene expression system were used to analyze potential splicing factors involved in the splicing event of PDCD1 exon 3. The potential binding motifs of heterogeneous nuclear ribonucleoprotein K (HNRNPK) on exon 3 predicted by SpliceAid were mutated by site-directed mutagenesis technology, which were further verified by pulldown assay. Antisense oligonucleotides (ASOs) targeting the exonic splicing silencer (ESS) on PDCD1 exon 3 were synthesized and screened to suppress the skipping of exon 3. The alternative splicing of PDCD1 exon 3 was analyzed by semiquantitative reverse transcription PCR. Western blot and flow cytometry were performed to detect the surface PD-1 expression in T cells. RESULTS: HNRNPK was screened as a key splicing factor that promoted PDCD1 exon 3 skipping, causing a decrease in flPD-1 expression on T cell membrane and an increase in sPD-1 expression. Mechanically, a key ESS has been identified on exon 3 and can be bound by HNRNPK protein to promote exon 3 skipping. Blocking the interaction between ESS and HNRNPK with an ASO significantly reduced exon 3 skipping. Importantly, HNRNPK can promote exon 3 skipping of mouse Pdcd1 gene as well. CONCLUSIONS: Our study revealed a novel evolutionarily conserved regulatory mechanism of PD-1 expression. The splicing factor HNRNPK markedly promoted PDCD1 exon 3 skipping by binding to the ESS on PDCD1 exon 3, resulting in decreased expression of flPD-1 and increased expression of sPD-1 in T cells.

Skeletal Muscle SIRT3 Deficiency Contributes to Pulmonary Vascular Remodeling in Pulmonary Hypertension Due to Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Pulmonary hypertension (PH) is a major complication linked to adverse outcomes in heart failure with preserved ejection fraction (HFpEF), yet no specific therapies exist for PH associated with HFpEF (PH-HFpEF). We have recently reported on the role of skeletal muscle SIRT3 (sirtuin-3) in modulation of PH-HFpEF, suggesting a novel endocrine signaling pathway for skeletal muscle modulation of pulmonary vascular remodeling. In this study, we attempted to define the processes by which skeletal muscle SIRT3 defects affect pulmonary vascular health in PH-HFpEF. METHODS AND RESULTS: Skeletal muscle-specific Sirt3 knockout mice (Sirt3skm-/-) exhibited reduced pulmonary vascular density accompanied by pulmonary vascular proliferative remodeling and elevated pulmonary pressures. Using mass spectrometry-based comparative secretome analysis, we demonstrated elevated secretion of LOXL2 (lysyl oxidase homolog 2) in SIRT3-deficient skeletal muscle cells. Elevated circulation and protein expression levels of LOXL2 were also observed in plasma and skeletal muscle of Sirt3skm-/- mice, a rat model of PH-HFpEF, and humans with PH-HFpEF. In addition, expression levels of CNPY2 (canopy fibroblast growth factor signaling regulator 2), a known proliferative and angiogenic factor, were increased in pulmonary artery endothelial cells and pulmonary artery smooth muscle cells of Sirt3skm-/- mice and animal models of PH-HFpEF. CNPY2 levels were also higher in pulmonary artery smooth muscle cells of subjects with obesity compared with nonobese subjects. Moreover, treatment with recombinant LOXL2 protein promoted pulmonary artery endothelial cell migration/proliferation and pulmonary artery smooth muscle cell proliferation through regulation of CNPY2-p53 signaling. Last, skeletal muscle-specific Loxl2 deletion decreased pulmonary artery endothelial cell and pulmonary artery smooth muscle cell expression of CNPY2 and improved pulmonary pressures in mice with high-fat diet-induced PH-HFpEF. CONCLUSIONS: This study demonstrates a systemic pathogenic impact of skeletal muscle SIRT3 deficiency in remote pulmonary vascular remodeling and PH-HFpEF. This study suggests a new endocrine signaling axis that links skeletal muscle health and SIRT3 deficiency to remote CNPY2 regulation in the pulmonary vasculature through myokine LOXL2. Our data also identify skeletal muscle SIRT3, myokine LOXL2, and CNPY2 as potential targets for the treatment of PH-HFpEF.

Plasma Proteomics Identifies B2M as a Regulator of Pulmonary Hypertension in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Pulmonary hypertension (PH) represents an important phenotype in heart failure with preserved ejection fraction (HFpEF). However, management of PH-HFpEF is challenging because mechanisms involved in the regulation of PH-HFpEF remain unclear. METHODS: We used a mass spectrometry-based comparative plasma proteomics approach as a sensitive and comprehensive hypothesis-generating discovery technique to profile proteins in patients with PH-HFpEF and control subjects. We then validated and investigated the role of one of the identified proteins using in vitro cell cultures, in vivo animal models, and independent cohort of human samples. RESULTS: Plasma proteomics identified high protein abundance levels of B2M (ß2-microglobulin) in patients with PH-HFpEF. Interestingly, both circulating and skeletal muscle levels of B2M were increased in mice with skeletal muscle SIRT3 (sirtuin-3) deficiency or high-fat diet-induced PH-HFpEF. Plasma and muscle biopsies from a validation cohort of PH-HFpEF patients were found to have increased B2M levels, which positively correlated with disease severity, especially pulmonary capillary wedge pressure and right atrial pressure at rest. Not only did the administration of exogenous B2M promote migration/proliferation in pulmonary arterial vascular endothelial cells but it also increased PCNA (proliferating cell nuclear antigen) expression and cell proliferation in pulmonary arterial vascular smooth muscle cells. Finally, B2m deletion improved glucose intolerance, reduced pulmonary vascular remodeling, lowered PH, and attenuated RV hypertrophy in mice with high-fat diet-induced PH-HFpEF. CONCLUSIONS: Patients with PH-HFpEF display higher circulating and skeletal muscle expression levels of B2M, the magnitude of which correlates with disease severity. Our findings also reveal a previously unknown pathogenic role of B2M in the regulation of pulmonary vascular proliferative remodeling and PH-HFpEF. These data suggest that circulating and skeletal muscle B2M can be promising targets for the management of PH-HFpEF.

A systematic review and meta-analysis of neoadjuvant imatinib use in locally advanced and metastatic gastrointestinal stromal tumors.

BACKGROUND: Several doubts remain regarding the optimal use of neoadjuvant imatinib in gastrointestinal stromal tumors (GISTs), such as ideal treatment duration, patient selection, and long-term survival outcomes. This manuscript provides a comprehensive review on neoadjuvant imatinib treatment outcomes and facilitate evidence-based decision-making for the use of imatinib therapy in GISTs. METHODS: Four databases (PubMed, EMBASE, Scopus, and Cochrane Library) were searched from inception to September 9, 2023. Meta-analyses of proportions were performed for the outcomes of R0 resection, disease responses, and 1-year, 3-year, and 5-year overall survival (OS) as well as 1-year, 3-year, and 5-year disease free survival (DFS). Sensitivity analyses in the form of leave-one-out analyses, meta-regression, and subgroup analyses were performed for outcomes with substantial statistical heterogeneity. RESULTS: The search yielded 1254 articles, and 36 studies were included in our analysis. Meta-analysis of proportions revealed that 1-year, 3-year, and 5-year OS was 100%, 94%, and 88%, while 1-year, 3-year and 5-year DFS was 99%, 89%, and 79%, respectively. An R0 resection rate of 89% and a disease response rate of 67% was achieved after a mean duration of treatment of 8.41 ± 0.367 months. KIT exon 9 mutation was significantly associated with poorer 5-year DFS. CONCLUSION: This study quantified key outcomes for neoadjuvant imatinib in locally advanced and metastatic or recurrent GIST. Patients with gastric and rectal tumous stand to benefit from neoadjuvant imatinib with an optimal treatment duration of 8 months. Furthermore, the potential utility of mutational analysis in guiding treatment with neoadjuvant imatinib was demonstrated.

A systematic review of the association between environmental risk factors and the development of irritable bowel syndrome.

BACKGROUND AND AIM: Irritable bowel syndrome (IBS) is a common gastrointestinal disorder with roots in genetic, immune, psychological, and dietary factors. Recently, the potential correlation between environmental exposures, such as air pollution, and IBS has gained attention. This review aimed to systematically examine existing studies on environmental factors associated with IBS, elucidating this interplay and guiding future research. METHODS: A literature search was conducted in Medline, EMBASE, Scopus, and Cochrane databases from database inception to October 10, 2023, using the keywords "Irritable Bowel" or IBS or "Irritable Colon" or "Mucous Colitis" or "Spastic Colitis" or "Spastic Colon" AND "environment* exposure*". Studies were included if they were original, published in English, described defined environmental exposure(s), and had documented diagnosis of IBS. For the purposes of this review, articles reporting physical (e.g. radiation and climate change), biological (e.g. bacteria and viruses), and chemical (e.g. harmful gases) exposures were included while psychological and dietary factors, which have been reviewed in detail elsewhere, are outside of the scope. RESULTS: A total of seven studies focusing on air quality, microbial exposure, and other environmental factors were reviewed. Studies highlighted a potential association between air pollutants and increased IBS incidence. Microbial exposure, post-natural disaster or due to poor sanitation, was linked to IBS development and gut dysbiosis. Other exposures, such as early pet ownership, were also associated with IBS risk. CONCLUSION: Existing research demonstrates an epidemiologic relationship between environmental exposures and the development of IBS. Further research is needed to understand these associations.

The relationship of health activation with risk of future cardiovascular disease among rural family caregivers of patients with chronic illnesses.

BACKGROUND: Family caregivers are at higher risk for developing cardiovascular disease (CVD) than non-caregivers. This risk is worse for those who live in rural compared to urban areas. Health activation, an indicator of engagement in self-care, is predictive of health outcomes and CVD risk in several populations. However, it is not known whether health activation is associated with CVD risk in rural caregivers of patients with chronic illnesses nor is it clear whether sex moderates any association. OBJECTIVES: Our aims were to determine (1) whether health activation independently predicts 10-year CVD risk; and (2) whether sex interacts with health activation in the prediction of 10-year CVD risk among rural family caregivers (N = 247) of patients with chronic illnesses. METHODS: Health activation was measured using the Patient Activation Measure. The predicted 10-year risk of CVD was assessed using the Framingham Risk Score. Data were analyzed using nonlinear regression analysis. RESULTS: Higher levels of health activation were significantly associated with decreased risk of developing CVD (p < 0.028). There was no interaction of sex with health activation on future CVD risk. However, male caregivers had greater risk of developing CVD in the next 10 years than female caregivers (p < 0.001). CONCLUSIONS: We demonstrated the importance of health activation to future CVD risk in rural family caregivers of patients with chronic illnesses. We also demonstrated that despite the higher risk of future CVD among male, the degree of association between health activation and CVD risk did not differ by sex.

Quantifying changes in oxygen saturation of the internal jugular vein in vivo using deep neural networks and subject-specific three-dimensional Monte Carlo models.

Central venous oxygen saturation (ScvO2) is an important parameter for assessing global oxygen usage and guiding clinical interventions. However, measuring ScvO2 requires invasive catheterization. As an alternative, we aim to noninvasively and continuously measure changes in oxygen saturation of the internal jugular vein (SijvO2) by a multi-channel near-infrared spectroscopy system. The relation between the measured reflectance and changes in SijvO2 is modeled by Monte Carlo simulations and used to build a prediction model using deep neural networks (DNNs). The prediction model is tested with simulated data to show robustness to individual variations in tissue optical properties. The proposed technique is promising to provide a noninvasive tool for monitoring the stability of brain oxygenation in broad patient populations.

Deficiency of the Deubiquitinase UCHL1 Attenuates Pulmonary Arterial Hypertension.

BACKGROUND: The ubiquitin-proteasome system regulates protein degradation and the development of pulmonary arterial hypertension (PAH), but knowledge about the role of deubiquitinating enzymes in this process is limited. UCHL1 (ubiquitin carboxyl-terminal hydrolase 1), a deubiquitinase, has been shown to reduce AKT1 (AKT serine/threonine kinase 1) degradation, resulting in higher levels. Given that AKT1 is pathological in pulmonary hypertension, we hypothesized that UCHL1 deficiency attenuates PAH development by means of reductions in AKT1. METHODS: Tissues from animal pulmonary hypertension models as well as human pulmonary artery endothelial cells from patients with PAH exhibited increased vascular UCHL1 staining and protein expression. Exposure to LDN57444, a UCHL1-specific inhibitor, reduced human pulmonary artery endothelial cell and smooth muscle cell proliferation. Across 3 preclinical PAH models, LDN57444-exposed animals, Uchl1 knockout rats (Uchl1-/-), and conditional Uchl1 knockout mice (Tie2Cre-Uchl1fl/fl) demonstrated reduced right ventricular hypertrophy, right ventricular systolic pressures, and obliterative vascular remodeling. Lungs and pulmonary artery endothelial cells isolated from Uchl1-/- animals exhibited reduced total and activated Akt with increased ubiquitinated Akt levels. UCHL1-silenced human pulmonary artery endothelial cells displayed reduced lysine(K)63-linked and increased K48-linked AKT1 levels. RESULTS: Supporting experimental data, we found that rs9321, a variant in a GC-enriched region of the UCHL1 gene, is associated with reduced methylation (n=5133), increased UCHL1 gene expression in lungs (n=815), and reduced cardiac index in patients (n=796). In addition, Gadd45α (an established demethylating gene) knockout mice (Gadd45α-/-) exhibited reduced lung vascular UCHL1 and AKT1 expression along with attenuated hypoxic pulmonary hypertension. CONCLUSIONS: Our findings suggest that UCHL1 deficiency results in PAH attenuation by means of reduced AKT1, highlighting a novel therapeutic pathway in PAH.

Effect of Stewing Time on the Small Molecular Metabolites, Free Fatty Acids, and Volatile Flavor Compounds in Chicken Broth.

Chicken broth has a taste of umami, and the stewing time has an important effect on the quality of chicken broth, but there are fewer studies on the control of the stewing time. Based on this, the study was conducted to analyze the effects of different stewing times on the sensory, small molecular metabolites, free fatty acids, and volatile flavor compounds contents in chicken broths by liquid chromatography-quadrupole/time-of-flight mass spectrometry, gas chromatography-mass spectrometry, headspace solid-phase microextraction, and gas chromatography-mass spectrometry. Eighty-nine small molecular metabolites, 15 free fatty acids, and 86 volatile flavor compounds were detected. Palmitic and stearic acids were the more abundant fatty acids, and aldehydes were the main volatile flavor compounds. The study found that chicken broth had the best sensory evaluation, the highest content of taste components, and the richest content of volatile flavor components when the stewing time was 2.5 h. This study investigated the effect of stewing time on the quality of chicken broth to provide scientific and theoretical guidance for developing and utilizing local chicken.

Photoinduced Copper-Catalyzed Asymmetric Three-Component Radical 1,2-Azidooxygenation of 1,3-Dienes.

Radical-involved multicomponent difunctionalization of 1,3-dienes has recently emerged as a promising strategy for rapid synthesis of valuable allylic compounds in one-pot operation. However, the expansion of radical scope and enantiocontrol remain two major challenges. Herein, we describe an unprecedented photoinduced copper-catalyzed highly enantioselective three-component radical 1,2-azidooxygenation of 1,3-dienes with readily available azidobenziodazolone reagent and carboxylic acids. This mild protocol exhibits a broad substrate scope, high functional group tolerance, and exceptional control over chemo-, regio- and enantioselectivity, providing practical access to diverse valuable azidated chiral allylic esters. Mechanistic studies imply that the chiral copper complex is implicated as a bifunctional catalyst in both the photoredox catalyzed azidyl radical generation and enantioselective radical C-O cross-coupling.

Enhancing vitamin D3 bioaccessibility: Unveiling hydrophobic interactions in soybean protein isolate and vitamin D3 binding via an infant in vitro digestion model.

In the domain of infant nutrition, optimizing the absorption of crucial nutrients such as vitamin D3 (VD3) is paramount. This study harnessed dynamic-high-pressure microfluidization (DHPM) on soybean protein isolate (SPI) to engineer SPI-VD3 nanoparticles for fortifying yogurt. Characterized by notable binding affinity (Ka = 0.166 × 105 L·mol-1) at 80 MPa and significant surface hydrophobicity (H0 = 3494), these nanoparticles demonstrated promising attributes through molecular simulations. During simulated infant digestion, the 80 MPa DHPM-treated nanoparticles showcased an impressive 74.4% VD3 bioaccessibility, delineating the pivotal roles of hydrophobicity, bioaccessibility, and micellization dynamics. Noteworthy was their traversal through the gastrointestinal tract, illuminating bile salts' crucial function in facilitating VD3 re-encapsulation, thereby mitigating crystallization and augmenting absorption. Moreover, DHPM treatment imparted enhancements in nanoparticle integrity and hydrophobic properties, consequently amplifying VD3 bioavailability. This investigation underscores the potential of SPI-VD3 nanoparticles in bolstering VD3 absorption, thereby furnishing invaluable insights for tailored infant nutrition formulations.

Risk factors, prognostic factors, and nomograms for distant metastasis in patients with diagnosed duodenal cancer: A population-based study.

BACKGROUND: Duodenal cancer is one of the most common subtypes of small intestinal cancer, and distant metastasis (DM) in this type of cancer still leads to poor prognosis. Although nomograms have recently been used in tumor areas, no studies have focused on the diagnostic and prognostic evaluation of DM in patients with primary duodenal cancer. AIM: To develop and evaluate nomograms for predicting the risk of DM and personalized prognosis in patients with duodenal cancer. METHODS: Data on duodenal cancer patients diagnosed between 2010 and 2019 were extracted from the Surveillance, Epidemiology, and End Results database. Univariate and multivariate logistic regression analyses were used to identify independent risk factors for DM in patients with duodenal cancer, and univariate and multivariate Cox proportional hazards regression analyses were used to determine independent prognostic factors in duodenal cancer patients with DM. Two novel nomograms were established, and the results were evaluated by receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). RESULTS: A total of 2603 patients with duodenal cancer were included, of whom 457 cases (17.56%) had DM at the time of diagnosis. Logistic analysis revealed independent risk factors for DM in duodenal cancer patients, including gender, grade, tumor size, T stage, and N stage (P < 0.05). Univariate and multivariate COX analyses further identified independent prognostic factors for duodenal cancer patients with DM, including age, histological type, T stage, tumor grade, tumor size, bone metastasis, chemotherapy, and surgery (P < 0.05). The accuracy of the nomograms was validated in the training set, validation set, and expanded testing set using ROC curves, calibration curves, and DCA curves. The results of Kaplan-Meier survival curves (P < 0.001) indicated that both nomograms accurately predicted the occurrence and prognosis of DM in patients with duodenal cancer. CONCLUSION: The two nomograms are expected as effective tools for predicting DM risk in duodenal cancer patients and offering personalized prognosis predictions for those with DM, potentially enhancing clinical decision-making.

Human Placenta-Derived Mesenchymal Stem Cells Improve Neurological Function in Rats with Intrauterine Hypoxic-Ischaemic Encephalopathy by Reducing Apoptosis and Inflammatory Reactions.

BACKGROUND: Hypoxic-ischaemic encephalopathy (HIE) is a major cause of neonatal disability and mortality. Although hypothermia therapy offers some neuroprotection, the recovery of neurological function is limited. Therefore, new synergistic therapies are necessary to improve the prognosis. Mesenchymal stem cell-based therapy is emerging as a promising treatment option for HIE. In this study, we studied the therapeutic efficacy of human placenta-derived mesenchymal stem cells (PD-MSCs) in the HIE rat model and analyzed the underlying therapeutic mechanisms. METHODS: Rats were divided into 6 groups (n = 9 for each) as follows: control, HIE model, HIE + normal saline, and HIE + PD-MSC transplantation at days 7, 14 and 28 postpartum. Following PD-MSC transplantation, neurological behavior was evaluated using rotarod tests, traction tests, and the Morris water maze test. The degree of brain tissue damage was assessed by histological examination and Nissl staining. Expression levels of apoptosis-related proteins and inflammatory factors were quantified by Western blotting and enzyme-linked immunosorbent assays. Immunofluorescence was used to investigate the ability of PD-MSCs to repair the morphology and function of hippocampal neurons with hypoxic-ischaemic (HI) injury. RESULTS: PD-MSC transplantation enhanced motor coordination and muscle strength in HIE rats. This treatment also improved spatial memory ability by repairing pathological damage and preventing the loss of neurons in the cerebral cortex. The most effective treatment was observed in the HIE + PD-MSC transplantation at day 7 group. Expression levels of microtubule-associated protein-2 (MAP-2), B-cell lymphoma-2 (BCL-2), interleukin (IL)-10, and transforming growth factor (TGF -ß1) were significantly higher in the HIE + PD-MSC treatment groups compared to the HIE group, whereas the levels of BCL-2-associated X protein (BAX), BCL-2-associated agonist of cell death (BAD), IL-1ß and tumour necrosis factor α (TNF-α) were significantly lower. CONCLUSIONS: We demonstrated that intravenous injection of PD-MSC at 7, 14 and 28 days after intrauterine HI damage in a rat model could improve learning, memory, and motor function, possibly by inhibiting apoptosis and inflammatory damage. These findings indicate that autologous PD-MSC therapy could have potential application for the treatment of HIE.