Variation of root traits and its influences on soil organic carbon stability in response to altered precipitation in an alpine meadow.

Soil organic carbon (SOC) dynamics are strongly controlled by plant roots. Yet, how variation of root traits under precipitation change influences SOC stability remains unclear. As part of a 5-year field experiment manipulating precipitation including 90 % (0.1P), 50 % (0.5P), 30 % (0.7P) decrease, and 50 % increase (1.5P), this study was designed to assess the effects of changing precipitation on root traits and production dynamics by minirhizotron and examine how such influences regulate SOC stability in an alpine meadow on the Qinghai-Tibetan Plateau. We found that root length density (RLD), specific root length (SRL), root branching intensity (RBI), and root residue carbon input (RC input) exhibited no significant response, whereas root turnover (RT), root carbon (C), nitrogen (N) concentrations and C/N ratio were altered by precipitation change with nonlinear trends. Absorptive root RT positively correlated to manipulated precipitation within the interannual precipitation range in topsoil, but it showed no significant change under extreme drought treatment. Alpine meadows can maintain the SOC content and density under varied precipitation. However, it showed significant variation in aggregate stability and organic carbon (OC) distribution in aggregates in topsoil, which were mainly due to the strong direct effects of soil moisture and partly related to RLD and RC input of transport roots. Although subsurface soil aggregate stability and OC associated with aggregates were not modified, our results indicated a risk of SOC stability variation in subsurface soil if absorptive root RT and SRL changed. These findings provide vital information to predict responses of SOC dynamics of alpine meadow to future climate change.

Primordial aminoacyl-tRNA synthetases preferred minihelices to full-length tRNA.

Aminoacyl-tRNA synthetases (AARS) and tRNAs translate the genetic code in all living cells. Little is known about how their molecular ancestors began to enforce the coding rules for the expression of their own genes. Schimmel et al. proposed in 1993 that AARS catalytic domains began by reading an 'operational' code in the acceptor stems of tRNA minihelices. We show here that the enzymology of an AARS urzyme•TΨC-minihelix cognate pair is a rich in vitro realization of that idea. The TΨC-minihelixLeu is a very poor substrate for full-length Leucyl-tRNA synthetase. It is a superior RNA substrate for the corresponding urzyme, LeuAC. LeuAC active-site mutations shift the choice of both amino acid and RNA substrates. AARS urzyme•minihelix cognate pairs are thus small, pliant models for the ancestral decoding hardware. They are thus an ideal platform for detailed experimental study of the operational RNA code.

Mitochondrial calcium uniporter promotes mitophagy by regulating the PINK1/Parkin pathway in caerulein­treated pancreatic ductal epithelial cells in vitro.

The mitochondrial calcium uniporter (MCU) is a major protein for the uptake of mitochondrial calcium to regulate intracellular energy metabolism, including processes such as mitophagy. The present study investigated the effect of the MCU on mitophagy in pancreatic ductal epithelial cells (PDECs) in acute pancreatitis (AP) in vitro. The normal human PDECs (HPDE6-C7) were treated with caerulein (CAE) to induce AP-like changes, with or without ruthenium red to inhibit the MCU. The mitochondrial membrane potentials (MMPs) and mitochondrial Ca2+ levels were analyzed by fluorescence. The expression levels of MCU, LC3, p62, and translocase of the outer mitochondrial membrane complex subunit 20 (TOMM20), putative kinase 1 (PINK1), and Parkin were measured by western blotting and immunofluorescence. Mitophagy was observed by confocal fluorescence microscopy and transmission electron microscopy. The results showed that CAE increased the MCU protein expression, mitochondrial Ca2+ levels, MMP depolarization and the protein expression of mitophagy markers including the LC3II/I ratio, PINK1, and Parkin. CAE decreased the protein expression of p62 and TOMM20, and promoted the formation of mitophagosomes in HPDE6-C7 cells. Notably, changes in these markers were reversed by inhibiting the MCU. In conclusion, an activated MCU may promote mitophagy by regulating the PINK1/Parkin pathway in PDECs in AP.

Effects and mechanisms of anti-diabetic dietary natural products: an updated review.

Diabetes is a global public health issue, characterized by an abnormal level of blood glucose. It can be classified into type 1, type 2, gestational, and other rare diabetes. Recent studies have reported that many dietary natural products exhibit anti-diabetic activity. In this narrative review, the effects and underlying mechanisms of dietary natural products on diabetes are summarized based on the results from epidemiological, experimental, and clinical studies. Some fruits (e.g., grape, blueberry, and cherry), vegetables (e.g., bitter melon and Lycium barbarum leaves), grains (e.g., oat, rye, and brown rice), legumes (e.g., soybean and black bean), spices (e.g., cinnamon and turmeric) and medicinal herbs (e.g., Aloe vera leaf and Nigella sativa), and vitamin C and carotenoids could play important roles in the prevention and management of diabetes. Their underlying mechanisms include exerting antioxidant, anti-inflammatory, and anti-glycation effects, inhibiting carbohydrate-hydrolyzing enzymes, enhancing insulin action, alleviating insulin resistance, modulating the gut microbiota, and so on. This review can provide people with a comprehensive knowledge of anti-diabetic dietary natural products, and support their further development into functional food to prevent and manage diabetes.

On-Chip Topological Photonic Crystal Nanobeam Filters.

We present an on-chip filter with a broad tailorable working wavelength and a single-mode operation. This is realized through the application of topological photonic crystal nanobeam filters employing synthesis parameter dimensions. By introducing the translation of air holes as a new synthetic parameter dimension, we obtained nanobeams with tunable Zak phases. Leveraging the bulk-edge correspondence, we identify the existence of topological cavity modes and establish a correlation between the cavity's interface morphology and working wavelength. Through experiments, we demonstrate filters with adjustable filtering wavelengths ranging from 1301 to 1570 nm. Our work illustrates the use of the synthetic translation dimension in the design of on-chip filters, and it holds potential for applications in other devices such as microcavities.

Mechanism of Self-Oxidative Copolymerization and its Application with Polydopamine-pyrrole Nano-copolymers.

Currently, the copolymer of dopamine (DA) and pyrrole (PY) via chemical and electrochemical oxidation usually requires additional oxidants, and lacks flexibility in regulating the size and morphology, thereby limiting the broad applications of DA-PY copolymer in biomedicine. Herein, the semiquinone radicals produced by the self-oxidation of DA is ingeniously utilized as the oxidant to initiate the following copolymerization with PY, and a series of quinone-rich polydopamine-pyrrole copolymers (PDAm -nPY) with significantly enhanced absorption in near-infrared (NIR) region without any additional oxidant assistance is obtained. Moreover, the morphology and size of PDAm -nPY can be regulated by changing the concentration of DA and PY, thereby optimizing nanoscale PDA0.05 -0.15PY particles (≈ 150 nm) with excellent NIR absorption and surface modification activity are successfully synthesized. Such PDA0.05 -0.15PY particles show effective photoacoustic (PA) imaging and photothermal therapy (PTT) against 4T1 tumors in vivo. Furthermore, other catechol derivatives can also copolymerize with PY under the same conditions. This work by fully utilizing the semiquinone radical active intermediates produced through the self-oxidation of DA reduces the dependence on external oxidants in the synthesis of composite materials and predigests the preparation procedure, which provides a novel, simple, and green strategy for the synthesis of other newly catechol-based functional copolymers.

Genomic database furnishes a spontaneous example of a functional Class II glycyl-tRNA synthetase urzyme.

The chief barrier to studies of how genetic coding emerged is the lack of experimental models for ancestral aminoacyl-tRNA synthetases (AARS). We hypothesized that conserved core catalytic sites could represent such ancestors. That hypothesis enabled engineering functional "urzymes" from TrpRS, LeuRS, and HisRS. We describe here a fourth urzyme, GlyCA, detected in an open reading frame from the genomic record of the arctic fox, Vulpes lagopus. GlyCA is homologous to a bacterial heterotetrameric Class II GlyRS-B. Alphafold2 predicted that the N-terminal 81 amino acids would adopt a 3D structure nearly identical to the HisRS urzyme (HisCA1). We expressed and purified that N-terminal segment. Enzymatic characterization revealed a robust single-turnover burst size and a catalytic rate for ATP consumption well in excess of that previously published for HisCA1. Time-dependent aminoacylation of tRNAGly proceeds at a rate consistent with that observed for amino acid activation. In fact, GlyCA is actually 35 times more active in glycine activation by ATP than the full-length GlyRS-B α-subunit dimer. ATP-dependent activation of the 20 canonical amino acids favors Class II amino acids that complement those favored by HisCA and LeuAC. These properties reinforce the notion that urzymes represent the requisite ancestral catalytic activities to implement a reduced genetic coding alphabet.

Preparation of porous superabsorbent particles based on starch by supercritical CO2 drying and its water absorption mechanism.

The slow water-absorption speed of starch-based superabsorbent resin (St-SAP) limits its application. In this study, porous St-SAP (P-St-SAP) was prepared by inverse suspension polymerization and supercritical CO2 drying, the aim is to provide a preparation method of fast absorbent resin. The P-St-SAP at 33 % starch content had an interpenetrating porous structure with macropores, mesopores and micropores, and the surface area, pore volume and average pore diameter were 32.06 m2·g-1, 0.116 cm3·g-1 and 21.6 nm, respectively. The water-absorption process included rapid-section, medium-section and slow-section, according with internal diffusion, double-constant and quasi second-order kinetic models, respectively. In the initial 30 s, a water-absorption speed of 262.6 g·g-1·min-1 in distilled water was much higher than some previous research results, and the equilibrium absorption value of 517.9 g·g-1 in distilled water and 72.9 g·g-1 in 0.9 % saline was better than that of non-porous St-SAP at similar starch content. Moreover, at the same stage the percentage of saline absorption ratio to equilibrium absorption value was 1.0- 2.0 times higher than that of distilled water. These research results indicate that the P-St-SAP has fast water-absorption speed and good salt resistance, which will have greater application prospects in sanitary materials, building concrete pouring, and flood control blocking piping.

Development and validation of a prognostic nomogram for predicting in-hospital mortality of patients with acute paraquat poisoning.

This study aimed to develop and validate a predictive model to determine the risk of in-hospital mortality in patients with acute paraquat poisoning. This retrospective observational cohort study included 724 patients with acute paraquat poisoning whose clinical data were collected within 24 h of admission. The primary outcome was in-hospital mortality. Patients were randomly divided into training and validation cohorts (7/3 ratio). In the training cohort, the least absolute shrinkage and selection operator regression models were used for data dimension reduction and feature selection. Multivariate logistic regression was used to generate a predictive nomogram for in-hospital mortality. The prediction model was assessed for both the training and validation cohorts. In the training cohort, decreased level of consciousness (Glasgow Coma Scale score < 15), neutrophil-to-lymphocyte ratio, alanine aminotransferase, creatinine, carbon dioxide combining power, and paraquat plasma concentrations at admission were identified as independent predictors of in-hospital mortality in patients with acute paraquat poisoning. The calibration curves, decision curve analysis, and clinical impact curves indicated that the model had a good predictive performance. It can be used on admission to the emergency department to predict mortality and facilitate early risk stratification and actionable measures in clinical practice after further external validation.

LARP1 knockdown inhibits cultured gastric carcinoma cell cycle progression and metastatic behavior.

This study aimed to clarify the role of la-related protein 1 (LARP1) in cell cycle progression and metastatic behavior of cultured gastric carcinoma (GC) cells. To do that, LARP1 expression was detected in clinical GC tissues and cell lines using quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting. The cell viability, apoptosis, cell cycle, migration, invasion, and cell growth were examined using a Cell Counting Kit-8, Annexin V-FITC staining, propidium iodide staining, Transwell migration and invasion assays, and colony formation assays after LARP1 knockdown. Phosphatidyl inositol 3-kinase (PI3K) and AKT1 mRNA and protein expression levels of PI3K, p-AKT1, AKT1, p-BAD, p-mTOR, and p21 in si-LARP1 transfected GC cells were determined using qRT-PCR and western blotting. Here, we've shown that LARP1 expression was upregulated in human GC tissues and KATO III cells. LARP1 knockdown inhibited GC cell proliferation, cell cycle progression, migration, invasion, and colony formation and promoted apoptosis. In si-LARP1-transfected KATO III cells, the mRNA expression levels of PI3K and AKT1, PI3K protein expression, and the p-AKT1/AKT1 ratio were significantly suppressed. p-mTOR and p-BAD were significantly decreased, whereas p21 was significantly increased in si-LARP1-transfected KATO III cells. In conclusion LARP1 knockdown induces apoptosis and inhibits cell cycle progression and metastatic behavior via PI3K/AKT1 signaling in GC cells.

Neutrophils are involved in early bone formation during midpalatal expansion.

OBJECTIVE: Midpalatal expansion (MPE) is routinely employed to treat transverse maxillary arch deficiency. Neutrophils are indispensable for recruiting bone marrow stromal cells (BMSCs) at the initial stage of bone regeneration. This study aimed to explore whether neutrophils participate in MPE and how they function during bone formation under mechanical stretching. MATERIALS AND METHODS: The presence and phenotype of neutrophils in the midpalatal suture during expansion were detected by flow cytometry and immunofluorescence staining. The possible mechanism of neutrophil recruitment and polarization was explored in vitro by exposing vascular endothelial cells (VECs) to cyclic tensile strain. RESULTS: The number of neutrophils in the distracted suture peaked on Day 3, and N2-type neutrophils significantly increased on Day 5 after force application. The depletion of circulatory neutrophils reduced bone volume by 43.6% after 7-day expansion. The stretched VECs recruited neutrophils via a CXCR2 mechanism in vitro, which then promoted BMSC osteogenic differentiation through the VEGFA/VEGFR2 axis. Consistently, these neutrophils showed higher expression of canonical N2 phenotype genes, including CD206 and Arg1. CONCLUSIONS: These results suggested that neutrophils participated in early bone formation during MPE. Based on these findings, we propose that stretched VECs recruited and polarized neutrophils, which, in turn, induced BMSC osteogenic differentiation.

Low BMI, blood calcium and vitamin D, kyphosis time, and outdoor activity time are independent risk factors for osteoporosis in postmenopausal women.

Aim: To explore the risk factors of osteoporosis in postmenopausal women in China. Method: This study collected all patient data from January 2014 to December 2015. Basic information and questionnaires were collected from 524 postmenopausal women in Sanya and Hainan Province. The questionnaire was administered to the enrolled participants by endocrinologists. Biochemical parameters were measured using fasting blood samples, and bone density was measured by dual energy X-ray absorptiometry at the department of radiology of Hainan hospital, PLA General Hospital. Participants with an R-value of ≤-2.5 were diagnosed with osteoporosis. After deleting missing values for each factor, 334 participants were divided into the osteoporosis (n=35) and non-osteoporosis (n=299) groups according to the R-values. Results: The participants had a median age of 60.8 years (range: 44-94 years). Among the 334 postmenopausal women included in this study, 35 (10.5%) were diagnosed with osteoporosis. Univariate analysis showed statistically significant differences in age, BMI, type of work, alkaline phosphatase, years of smoking, blood calcium levels, kyphosis, fracture, and asthma between the two groups (P<0.05). In addition, multivariate logistic analysis showed that age (odds ratio [OR]: 1.185, 95% confidence interval [CI]: 1.085-1.293, P<0.001) and kyphosis times (OR:1.468, 95% CI: 1.076-2.001, P=0.015) were positively correlated with postmenopausal osteoporosis, whereas BMI (OR: 0.717, 95% CI: 0.617-0.832, P<0.001), blood calcium levels (OR: 0.920, 95% CI: 0.854-0.991, P=0.027), vitamin D levels (OR: 0.787, 95% CI: 0.674-0.918, P=0.002), and outdoor activity time (OR: 0.556, 95% CI: 0.338-0.915, P=0.021) were negatively correlated with postmenopausal osteoporosis. Conclusion: Low BMI, blood calcium and vitamin D levels, kyphosis time, and outdoor activity time are independent risk factors for osteoporosis in postmenopausal women.

Copper-Catalyzed Fluoroalkylphosphorothiolation of Alkynes for the Synthesis of (E)-ß-Fluoroalkyl Vinyl Phosphorothioates.

A convenient copper-catalyzed three-component radical-based fluoroalkylphosphorothiolation of terminal alkynes with (iPrO)2P(O)SH and fluoroalkylation reagent for the synthesis of a variety of (E)-ß-fluoroalkyl vinyl phosphorothioates with excellent regioselectivity and stereoselectivity has been developed. All the starting materials used in this reaction are highly stable and readily available. Thus, this process features with mild reaction conditions, simple operation and good functional group tolerance (>40 examples). Furthermore, this modular reaction system allows the late-stage functionalization of bioactive molecules.

Depuration and Starvation Regulate Metabolism and Improve Flesh Quality of Yellow Catfish (Pelteobagrus fulvidraco).

Fat deposition and off-flavor in the muscle are the main problems affecting flesh quality in aquaculture fish, especially in catfish, leading to low acceptability and reduced market price. Yellow catfish is an important aquaculture fish in China. In this study, 40 days of depuration and starvation treatment were explored to improve the muscle quality of aquaculture yellow catfish. After depuration and starvation, the body weight, condition factor (CF) and mesenteric fat index (MFI) were all significantly decreased 20 days after treatment. The metabolomic profiles in muscle were characterized to analyze the muscle quality in yellow catfish. The results showed that the content of ADP, AMP, IMP, glutamic acid and taurine were significantly increased between 20 and 40 days post-treatment in the muscle of yellow catfish during the treatment, which was positively associated with the flesh tenderness and quality. In contrast, aldehydes and ketones associated with off-flavors and corticosterone associated with bitter taste were all decreased at 20 days post-treatment. Considering the balance of body weight loss and flesh quality improvement, depuration and starvation for around 20 days is suitable for aquaculture yellow catfish. Our study not only provides an effective method to improve the flesh quality of aquaculture yellow catfish but also reveals the potential mechanism in this process.

Corrigendum: Zilucoplan, a macrocyclic peptide inhibitor of human complement component 5, uses a dual mode of action to prevent terminal complement pathway activation.

[This corrects the article DOI: 10.3389/fimmu.2023.1213920.].

Genomic prediction of pig growth traits based on machine learning.

This study aimed to assess and compare the performance of different machine learning models in predicting selected pig growth traits and genomic estimated breeding values (GEBV) using automated machine learning, with the goal of optimizing whole-genome evaluation methods in pig breeding. The research employed genomic information, pedigree matrices, fixed effects, and phenotype data from 9968 pigs across multiple companies to derive four optimal machine learning models: deep learning (DL), random forest (RF), gradient boosting machine (GBM), and extreme gradient boosting (XGB). Through 10-fold cross-validation, predictions were made for GEBV and phenotypes of pigs reaching weight milestones (100 kg and 115 kg) with adjustments for backfat and days to weight. The findings indicated that machine learning models exhibited higher accuracy in predicting GEBV compared to phenotypic traits. Notably, GBM demonstrated superior GEBV prediction accuracy, with values of 0.683, 0.710, 0.866, and 0.871 for B100, B115, D100, and D115, respectively, slightly outperforming other methods. In phenotype prediction, GBM emerged as the best-performing model for pigs with B100, B115, D100, and D115 traits, achieving prediction accuracies of 0.547, followed by DL at 0.547, and then XGB with accuracies of 0.672 and 0.670. In terms of model training time, RF required the most time, while GBM and DL fell in between, and XGB demonstrated the shortest training time. In summary, machine learning models obtained through automated techniques exhibited higher GEBV prediction accuracy compared to phenotypic traits. GBM emerged as the overall top performer in terms of prediction accuracy and training time efficiency, while XGB demonstrated the ability to train accurate prediction models within a short timeframe. RF, on the other hand, had longer training times and insufficient accuracy, rendering it unsuitable for predicting pig growth traits and GEBV.

Fabrication of 3D printed PCL/PEG artificial bile ducts as supportive scaffolds to promote regeneration of extrahepatic bile ducts in a canine biliary defect model.

In this study, a 3D porous poly(ε-caprolactone)/polyethylene glycol (PCL/PEG) composite artificial tubular bile duct was fabricated for extrahepatic bile duct regeneration. PCL/PEG composite scaffolds were fabricated by 3D printing, and the molecular structure, mechanical properties, thermal properties, morphology, and in vitro biocompatibility were characterized for further application as artificial bile ducts. A bile duct defect model was established in beagle dogs for in vivo implantation. The results demonstrated that the implanted PE1 ABD, serving as a supportive scaffold, effectively stimulated the regeneration of a new bile duct comprising CK19-positive and CK7-positive epithelial cells within 30 days. Remarkably, after 8 months, the newly formed bile duct exhibited an epithelial layer resembling the normal structure. Furthermore, the study revealed collagen deposition, biliary muscular formation, and the involvement of microvessels and fibroblasts in the regenerative process. In contrast, the anastomotic area without ABD implantation displayed only partial restoration of the epithelial layer, accompanied by fibroblast proliferation and subsequent bile duct fibrosis. These findings underscore the limited inherent repair capacity of the bile duct and underscore the beneficial role of the PE1 ABD artificial tubular bile duct in promoting biliary regeneration.

Thermoresponsive swelling of photoacoustic single-chain nanoparticles.

NIR-fluorescent LCST-type single-chain nanoparticles (SCNPs) change their photophysical behaviour upon heating, caused by depletion of water from the swollen SCNP interiors. This thermoresponsive effect leads to a fluctuating photoacoustic (PA) signal which can be used as a contrast mechanism for PA imaging.

Zilucoplan, a macrocyclic peptide inhibitor of human complement component 5, uses a dual mode of action to prevent terminal complement pathway activation.

Introduction: The complement system is a key component of the innate immune system, and its aberrant activation underlies the pathophysiology of various diseases. Zilucoplan is a macrocyclic peptide that binds and inhibits the cleavage/activation of human complement component 5 (C5). We present in vitro and ex vivo data on the mechanism of action of zilucoplan for the inhibition of C5 activation, including two clinically relevant C5 polymorphisms at R885. Methods: The interaction of zilucoplan with C5, including for clinical C5 R885 variants, was investigated using surface plasmon resonance (SPR), hemolysis assays, and ELISA. The interference of C5b6 formation by zilucoplan was investigated by native gel analysis and hemolysis assay. The permeability of zilucoplan in a reconstituted basement membrane was assessed by the partition of zilucoplan on Matrigel-coated transwell chambers. Results: Zilucoplan specifically bound human complement C5 with high affinity, competitively inhibited the binding of C5 to C3b, and blocked C5 cleavage by C5 convertases and the assembly of the cytolytic membrane attack complex (MAC, or C5b9). Zilucoplan fully prevented the in vitro activation of C5 clinical variants at R885 that have been previously reported to respond poorly to eculizumab treatment. Zilucoplan was further demonstrated to interfere with the formation of C5b6 and inhibit red blood cell (RBC) hemolysis induced by plasmin-mediated non-canonical C5 activation. Zilucoplan demonstrated greater permeability than a monoclonal C5 antibody in a reconstituted basement membrane model, providing a rationale for the rapid onset of action of zilucoplan observed in clinical studies. Conclusion: Our findings demonstrate that zilucoplan uses a dual mode of action to potently inhibit the activation of C5 and terminal complement pathway including wild-type and clinical R885 variants that do not respond to eculizumab treatment. These data may be relevant to the clinically demonstrated benefits of zilucoplan.

Association of ultra-processed foods consumption with risk of cardio-cerebrovascular disease: A systematic review and meta-analysis of cohort studies.

AIMS: The epidemiological evidence regarding the impact of ultra-processed foods (UPFs) on the risk of cardio-cerebrovascular diseases (CCVDs) is controversial. The aim of this systematic review and meta-analysis is to examine the association between UPF consumption and the risk of CCVDs within cohort studies. DATA SYNTHESIS: A systematic literature search was conducted across multiple databases, including PubMed/Medline, Embase, Web of Science, Scopus, and the Cochrane Library databases, covering the inception of these databases up until January 1st, 2023. A total of 39 cohort studies involving 63,573,312 human participants were deemed eligible according to the inclusion criteria. Utilizing random-effects models, risk ratios (RRs) were estimated to determine the pooled results. Our findings indicate a significant association between a higher consumption of UPF and an increased likelihood of CCVDs (RR: 1.08, 95% CI: 1.01-1.16, I2 = 89%; p < 0.01) compared to individuals who either abstain from or consume lesser amounts of UPF. Nonlinear dose-response meta-analyses showed that a consistent high intake of UPFs was associated with an elevated risk of developing CCVDs (p non-linearity <0.001). Notably, the risk of CCVDs escalated by approximately 7% with an UPF intake of up to 1 serving per day. Subgroup analysis further revealed a significant augmentation in the risk of total CVD and hypertension with increased UPF consumption. CONCLUSIONS: A higher intake of UPF significantly increases the risk of developing CCVDs. Prospective studies controlling for confounding factors are needed to validate the relationship between UPF intake and the development of CCVDs.