MMP-1, MMP-8, and MMP-13 Gene Polymorphisms and Haplotype Is a Risk Factor for Dupuytren Contracture: A Case-Control Study.

BACKGROUND: There is an increased tissue expression of matrix metalloproteinases (MMPs) on Dupuytren contracture (DC). Genetic polymorphisms (single nucleotide polymorphism [SNPs]) in genes of these enzymes may individually influence these transcriptions. Haplotype analysis, which is the observation of a group of alleles, could be more useful to identify the association between SNPs and DC. The purpose of this study was to evaluate the influence of MMP-1 g.-1607 G>GG (rs1799750), MMP-8 g.-799 C>T (rs11225395), and MMP-13 g.-77 A>G (rs2252070) SNPs individually and in haplotype on DC. METHODS: A total of 60 patients with a clinical diagnosis of DC were evaluated and matched, according to age and gender, with the control group of 100 patients without this clinical diagnosis. Genomic DNA was extracted from saliva samples, and genotypes were obtained by polymerase chain reaction-restriction fragment length polymorphism. Statistical analysis of the results included Mann-Whitney U test, Chi-squared test, and PHASE and R software, with a significance level of 5%. RESULTS: The 3 SNPs studied showed significant differences in allele and genotype frequencies between the groups: 2G in MMP-1 (P = .018; odds ratio [OR] 1.80 (95% confidence interval [CI], 1.13-2.88)), T in MMP-8 (P = .015; OR 0.53 (95% CI, 0.33-0.88)), and A in MMP-13 (rs2252070) SNPs (P = .040, OR 0.54 (95% CI, 0.33-0.90)) are risk alleles. The global haplotype analysis indicated a significant difference between both groups. CONCLUSIONS: In conclusion, MMP-1 g.-1607 G>GG (rs1799750), MMP-8 g.-799 C>T (rs11225395), and MMP-13 g.-77 A>G (rs2252070) SNPs, individually and in haplotype, are a risk factor for DC, indicating that these SNPs may be a potential diagnostic and prognostic factor for DC.

Discovery of tumor-reactive T cell receptors by massively parallel library synthesis and screening.

T cell receptor (TCR) gene therapy is a potent form of cellular immunotherapy in which patient T cells are genetically engineered to express TCRs with defined tumor reactivity. However, the isolation of therapeutic TCRs is complicated by both the general scarcity of tumor-specific T cells among patient T cell repertoires and the patient-specific nature of T cell epitopes expressed on tumors. Here we describe a high-throughput, personalized TCR discovery pipeline that enables the assembly of complex synthetic TCR libraries in a one-pot reaction, followed by pooled expression in reporter T cells and functional genetic screening against patient-derived tumor or antigen-presenting cells. We applied the method to screen thousands of tumor-infiltrating lymphocyte (TIL)-derived TCRs from multiple patients and identified dozens of CD4+ and CD8+ T-cell-derived TCRs with potent tumor reactivity, including TCRs that recognized patient-specific neoantigens.

Deficiency in SLC25A15, a hypoxia-responsive gene, promotes hepatocellular carcinoma by reprogramming glutamine metabolism.

BACKGROUND & AIMS: The role of solute carrier family 25 member 15 (SLC25A15), a critical component of the urea cycle, in hepatocellular carcinoma (HCC) progression remains poorly understood. This study investigated the impact of SLC25A15 on HCC progression and its mechanisms. METHODS: We systematically investigated the function of SLC25A15 in HCC progression using large-scale data mining and cell, animal, and organoid models. Furthermore, we analyzed its involvement in reprogramming glutamine metabolism. RESULTS: SLC25A15 expression was significantly decreased in HCC tissues, and patients with low SLC25A15 levels had a poorer prognosis. Hypoxia-exposed HCC cells or tissues had lower SLC25A15 expression. A positive correlation between HNF4A, a transcription factor suppressed by hypoxia, and SLC25A15 was observed in both HCC tissues and cells. Modulating HNF4A levels altered SLC25A15 mRNA levels. SLC25A15 upregulated SLC1A5, increasing glutamine uptake. The reactive metabolic pathway of glutamine was increased in SLC25A15-deficient HCC cells, providing energy for HCC progression through additional lipid synthesis. Ammonia accumulation due to low SLC25A15 levels suppressed the expression of OGDHL (oxoglutarate dehydrogenase L), a switch gene that mediates SLC25A15 deficiency-induced reprogramming of glutamine metabolism. SLC25A15-deficient HCC cells were more susceptible to glutamine deprivation and glutaminase inhibitors. Intervening in glutamine metabolism increased SLC25A15-deficient HCC cells' response to anti-PD-L1 treatment. CONCLUSION: SLC25A15 is hypoxia-responsive in HCC, and low SLC25A15 levels result in glutamine reprogramming through SLC1A5 and OGDHL regulation, promoting HCC progression and regulating cell sensitivity to anti-PD-L1. Interrupting the glutamine-derived energy supply is a potential therapeutic strategy for treating SLC25A15-deficient HCC. IMPACT AND IMPLICATIONS: We first demonstrated the tumor suppressor role of solute carrier family 25 member 15 (SLC25A15) in hepatocellular carcinoma (HCC) and showed that its deficiency leads to reprogramming of glutamine metabolism to promote HCC development. SLC25A15 can serve as a potential biomarker to guide the development of precision therapeutic strategies aimed at targeting glutamine deprivation. Furthermore, we highlight that the use of an inhibitor of glutamine utilization can enhance the sensitivity of low SLC25A15 HCC to anti-PD-L1 therapy.

The improvement of tyrosol bioavailability by encapsulation into liposomes using pH-driven method.

To improve the poor water solubility and oral bioavailability of tyrosol, novel tyrosol liposomes (Tyr-LPs) were prepared by pH-driven method. Fourier transform infrared (FTIR) absorption spectra and X-ray diffraction (XRD) analysis indicated that Tyr-LPs were successfully encapsulated and tyrosol was in an amorphous state in liposomes. When tyrosol content in Tyr-LP was 1.33 mg/ml and the Tyr:LP (mass ratio) = 1:2, favorable dispersibility of Tyr-LP was exhibited, with an instability index of 0.049 ± 0.004, PDI of 0.274 ± 0.003, and the EE of 94.8 ± 2.5 %. In vivo pharmacokinetic studies showed that after oral administration of tyrosol or Tyr-LP (Tyr:LP = 1:2), concentration-versus-time curve (AUC0-720mins) and maximum concentration (Cmax) values of Tyr-LP was respectively 1.5-fold (P < 0.01) and 2.25-fold (P < 0.01) higher than tyrosol, which indicated that the oral bioavailability of tyrosol was effectively improved in Tyr-LPs. Our study thereby provides theoretical support for the application of Tyr-LP for optimal delivery of tryosol.

Dynamic changes at high-protein dietary pattern of major fatty acids in healthy lactating women: A systematic review and meta-analysis.

BACKGROUND: Fatty acids (FAs) in human milk are important nutrients for infants. They play important roles in energy supply, nervous system development, and metabolic function maintenance. However, how the composition of major milk FAs change with lactation stages remains controversial. OBJECTIVES: To systematically review the concentration range of major FAs in human milk at various lactation stages. METHODS: A total of 12 papers involving 50 sets of data with 3507 participants were reviewed according to the PRISMA checklist and flow diagram. The inclusion criteria was the literatures had the FAs contents in breast milk of healthy lactation mothers at three lactation stages and the dietary patterns could be calculated. The exclusion criteria were: the studies were duplicates, were unrelated to dietary patterns or breast milk composition, and/or the study populations were unhealthy. We searched PubMed, the China National Knowledge Infrastructure, WanFang, and Web of science. Agency for Health Care Research and Quality (AHRQ) was used to assess the bias of studies. The mean values of polyunsaturated fatty acids (PUFAs) including docosahexaenoic acid (DHA), arachidonic acid (AA), eicosapentaenoic acid (EPA), α-linolenic acid (ALA), linoleic acid (LA), monounsaturated fatty acids (MUFAs), and saturated fatty acids (SFAs, including lauric acid and palmitic acid), in human milk at three lactation stages (colostrum 1-7 d, transitional milk 8-14 d, mature milk 15 d-3 mo) of healthy lactating women were investigated in terms of the high protein dietary pattern. Publication biases were evaluated by Egger's test. RESULTS: According to the percentage in total fat of colostrum, transitional milk, and mature milk (% wt/wt), respectively, the results showed that PUFA (25.72%, 24.92%, and 22.69%), AA (0.85%, 0.76%, and 0.59%), DHA (0.53%, 0.47%, and 0.39%), EPA (0.15%, 0.10%, and 0.10%), and MUFA (37.39%, 37.21%, and 36.14%) contents in breast milk decreased with lactation, while another two PUFA forms, LA (17.47%, 17.82%, and 17.48%), and ALA (1.09%, 1.39%, and 1.24%) arrived at a peak in the transitional milk and then decreased in the mature milk, SFA (37.46%, 38.64%, and 40.52%), and lauric acid contents (2.78%, 4.91%, and 4.97%) increased with the lactation stages. CONCLUSION: These findings could shed light on the dynamic change progress of major FA metabolism, potentially enhancing the knowledge of lactation biology, and improving infant feeding practices to meet their needs.

Multi-average high-acceleration modified volumetric interpolated breath-hold examination (VIBE) for free-breathing multiphase contrast-enhanced liver MRI: a comparative study with breath-hold VIBE.

BACKGROUND: Breath-hold volumetric interpolated breath-hold examination (BH-VIBE) of multiphase contrast-enhanced liver magnetic resonance imaging (MPCE-LMRI) requires good cooperative individuals to comply with multiple breath-holds. PURPOSE: To develop a free-breathing modified VIBE (FB-mVIBE) as a substitute of BH-VIBE in MPCE-LMRI. MATERIAL AND METHODS: We modified VIBE with a high acceleration factor (2 × 2) and four averages to produce the mVIBE scan. A total of 90 individuals (40 men; mean age = 54.6 ± 10.0 years) who had received MPCE-LMRI as part of a voluntary health check-up for oncology survey were enrolled. Each participant was scanned in four phases (pre-contrast, arterial phase, venous phase, and delay phase), and each phase had two sequential scans. To encounter the timing effect of contrast enhancement, three scan orders were designed: BH-VIBE and FB-mVIBE (group A, n = 30); BH-VIBE and FB-VIBE (group B, n = 30); and FB-mVIBE and BH-VIBE (group C, n = 30). The comparisons included the objective measurements and 25 visual-score by two abdominal radiologists independently. RESULTS: Consistency between raters was observed for all three sequences (intraclass correlation coefficient [ICC] = 0.741-0.829). For rater 1, the mean scores of FB-mVIBE (23.67 ± 1.32) were equal to those of BH-VIBE (23.83 ± 1.98) in groups C and B (P = 0.852). The mean scores of FB-mVIBE (22.07 ± 3.02), but significantly higher than those of FB-VIBE (14.7 ± 3.41) in groups A and B (P <0.001). Similar scores were found for rater 2. The objective measurement of FB-mVIBE were equal to or higher than BH-VIBE and markedly superior to FB-VIBE. CONCLUSION: FB-mVIBE is a practical alternative to BH-VIBE for individuals who cannot cooperate with multiple breath-holds for MPCE-LMRI.

1,3-Dioleoyl-2-palmitoyl-glycerol and 1-oleoyl-2-palmitoyl-3-linoleoyl-glycerol: Structure-function relationship, triacylglycerols preparation, nutrition value.

Based on multivariate statistics, this review compared major triacylglycerols (TAGs) in animal milk and human milk fat from China and other countries. Human milk fat differs from animal milk fat in that it has longer acyl chains and higher concentrations of 1,3-dioleoyl-2-palmitoyl-glycerol (O-P-O) and 1-oleoyl-2-palmitoyl-3-linoleoylglycerol (O-P-L). O-P-L is a significant and distinct TAG in human milk fat, particularly in China. 1-oleoyl-2-palmitoyl-3-linoleoylglycerol (OPL) is human milk's major triglyceride molecule of O-P-L, accounting for more than 70%. As a result, OPL has piqued the interest of Chinese academics. The synthesis process and nutritional outcomes of OPL have been studied, including changes in gut microbiota, serum lipid composition, improved fatty acid and calcium absorption, and increased total bile acid levels. However, current OPL research is limited. Therefore, this review discussed enzymatic preparation of 1,3-dioleoyl-2-palmitoyl-glycerol (OPO) and OPL and their nutritional and physiological activity to direct future research direction for sn-2 palmitate and OPL.

Differences in Absorption and Metabolism between Structured 1,3-Oleate-2-palmitate Glycerol and 1-Oleate-2-palmitate-3-linoleate Glycerol on C57BL/6J Mice.

This study investigated differences in absorption and metabolism between 1,3-oleate-2-palmitate glycerol (OPO) and 1-oleate-2-palmitate-3-linoleate glycerol (OPL) using C57BL/6J mice. OPL was associated with higher postprandial plasma total triacylglycerol (TG), low-density lipoprotein cholesterol (LDL-C) concentrations, and the ratio of LDL-C to high-density lipoprotein cholesterol (HDL-C) compared to those of OPO (p > 0.05). OPO significantly increased postprandial oleic acid (OA) concentrations compared to OPL over the entire monitoring period (p < 0.05), while OPL significantly elevated linoleic acid (LA) levels compared to OPO (p < 0.05). After 1 month of feeding, the mice in both OPO and OPL groups showed lower final weight, weight gain, and liver TG, LDL-C, and LDL/HDL concentrations compared to the control (soybean oil) group. Lipidomics results showed that OPO increased the biosynthesis of very long-chain fatty acids and decreased the abundance of AcCa (16:1), AcCa (18:2), AcCa (18:1), AcCa (16:0), CarE (16:0), and CarE (16:1) relative to OPL. These lipid metabolites were positively correlated with liver TG, LDL-C, and LDL/HDL levels and negatively related to peroxisome proliferator-activated receptors α (PPARα) and acyl-CoA oxidase (ACOX1) expression. This study showed differences in physiologic functions between OPO and OPL and provided support for the future application of OPL in infant formula.

The digestion and absorption characteristics of human milk phospholipid analogs: a combination study between in vitro and in vivo.

Phospholipids play a crucial role in the growth and neurodevelopment of infants. Currently, soybean phospholipids (SPLs) are the common phospholipid component in most infant formulas (IFs), which, however, shows an obvious difference with the phospholipid (PL) composition of human milk fat. Therefore, in the present study, human milk phospholipid analogs (HMPAs) were prepared by mimicking the composition of PE, PC, PI, PS, and SM in breast milk phospholipids and the composition of the major fatty acids (C16:0, C18:0, C18:1, and C18:2), and their digestion and absorption characteristics were explored using in vitro and mice models. The prepared HMPA contained 26.48% PE, 24.64% PC, 36.19% SM, 6.35% PI, and 6.32% PS, with 40.51% C16:0, 17.02% C18:0, 29.19% C18:1, and 13.26% C18:2, showing different digestive properties relative to SPL. There was little effect on the physical and chemical properties of HMPA under in vitro gastric conditions. The hydrolysis degree, fatty acids release rate, and average particle size decreasing rate of HMPA was significantly higher than that of SPL during digestion in vitro intestine (P < 0.05), showing better digestive process relative to SPL. In terms of the mice model, HMPA had a higher hydrolysis degree in the intestinal tract. Based on the area under curve (AUC) analysis of serum fatty acids, it was found that despite HMPA being absorbed at a slower rate than SPL, it was absorbed more than SPL. In summary, the digestion and absorption of HMPA were preferred to SPL, and these obtained results might provide a theoretical basis for the development and utilization of HMPA in IF.

Development of Polyvinyl Alcohol/Polyethylene Glycol Copolymer-based Orodispersible Films Loaded with Entecavir: Formulation and In vitro Characterization.

PURPOSE: The aim of the study is to prepare entecavir (ETV)-loaded orodispersible films (ODFs) using polyvinyl alcohol (PVA)/polyethylene glycol (PEG) graft copolymer (Kollicoat® IR) as a film-forming agent, and further to evaluate the dissolution rate, mechanical and physicochemical properties of films. METHODS: ETV-ODFs were prepared by a solvent casting method. The amount of film-forming agent, plasticizer, and disintegrating agent was optimized in terms of the appearance, thickness, disintegration time and mechanical properties of ODFs. The compatibility between the drug and each excipient was conducted under high temperature (60 °C), high humidity (RH 92.5%), and strong light (4500 Lx) for 10 days. The dissolution study of optimal ODFs compared with the original commercial tablet (Baraclude®) was performed using a paddle method in pH 1.0, pH 4.5, pH 6.8, and pH 7.4 media at 37 °C. The morphology of ODFs was observed via scanning electron microscopy (SEM). The mechanical properties such as tensile strength (TS), elastic modulus (EM), and percentage elongation (E%) of ODFs were evaluated using the universal testing machine. The physicochemical properties of ODFs investigated using X-ray diffraction (XRD), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FT-IR). RESULTS: The related substances were less than 0.5% under high temperature, high humidity, and strong light for 10 days when ETV was mixed with excipients. The optimal formulation of ODFs was set as the quality ratio of Kollicoat® IR, glycerol, sodium alginate (ALG-Na): TiO2: MCC+CMC-Na: ETV was 60:9:12:1:1:1. The drug-loaded ODFs were white and translucent with excellent stripping property. The thickness, disintegration time, EM, TS, and E% were 103.33±7.02 µm, 25.31±1.95 s, 25.34±8.69 Mpa, 2.14±0.26 Mpa, and 65.45±19.41 %, respectively. The cumulative drug release from ODFs was more than 90% in four different media at 10 min. The SEM showed that the drug was highly dispersible in ODFs, and the XRD, DSC, and FT-IR results showed that there occurred some interactions between the drug and excipients. CONCLUSION: In conclusion, the developed ETV-loaded ODFs showed relatively short disintegration time, rapid drug dissolution, and excellent mechanical properties. This might be an alternative to conventional ETV Tablets for the treatment of chronic hepatitis B.

Histological Compatibility in Distal Neurotizations: A Systematic Review.

Considering the importance of defining the minimum number of axons between recipient and donor branches, that is, the definition of histological compatibility in distal neurotizations for the success of the procedure and the surgeon's freedom to choose individualized strategies for each patient, this systematic review was conducted to find out the most recent studies on the subject. The objective of this systematic review was to determine the importance of the number of axons and the relationship between axon counts in the donor and recipient nerves in the success of nerve transfer. A literature review was performed on five international databases: Web of Science, Scopus, Wiley (Cochrane Database), Embase, and PubMed. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed (2020 version), a guide designed to guide the elaboration of systematic literature reviews. One hundred and fifty-seven studies were found, and 23 were selected based on the eligibility criteria. The articles presented were conclusive in determining the importance of the number of axons in the success of nerve transfer. Still, the relationship between the number of axons in the donor and recipient nerves seems more relevant in the success of transfers and is not always explored by the authors. The review of the articles has provided compelling evidence that the number of axons is a critical determinant of the success of nerve transfer procedures. However, the relationship between the number of axons in the donor nerve and that in the recipient nerve appears to be even more crucial for successful transfers, a factor that is not always adequately explored by authors in the existing literature. Level of evidence : Level IV, therapeutic study.

Effect of whole body vibration therapy in the rat model of steroid-induced osteonecrosis of the femoral head.

Background: Steroid-induced Osteonecrosis of the Femoral Head (SIONFH) is a skeletal disease with a high incidence and a poor prognosis. Whole body vibration therapy (WBVT), a new type of physical training, is known to promote bone formation. However, it remains unclear whether WBVT has a therapeutic effect on SIONFH. Materials and methods: Thirty adult male and female Sprague-Dawley (SD) rats were selected and randomly assigned to three experimental groups: the control group, the model group, and the mechanical vibration group, respectively. SIONFH induction was achieved through the combined administration of lipopolysaccharides (LPS) and methylprednisolone sodium succinate for injection (MPS). The femoral head samples underwent hematoxylin and eosin (H&E) staining to visualize tissue structures. Structural parameters of the region of interest (ROI) were compared using Micro-CT analysis. Immunohistochemistry was employed to assess the expression levels of Piezo1, BMP2, RUNX2, HIF-1, VEGF, CD31, while immunofluorescence was used to examine CD31 and Emcn expression levels. Results: The H&E staining results revealed a notable improvement in the ratio of empty lacuna in various groups following WBVT intervention. Immunohistochemical analysis showed that the expression levels of Piezo1, BMP2, RUNX2, HIF-1, VEGF, and CD31 in the WBVT group exhibited significant differences when compared to the Model group (p < 0.05). Additionally, immunofluorescence analysis demonstrated statistically significant differences in CD31 and Emcn expression levels between the WBVT group and the Model group (p < 0.05). Conclusion: WBVT upregulates Piezo1 to promote osteogenic differentiation, potentially by enhancing the HIF-1α/VEGF axis and regulating H-vessel angiogenesis through the activation of the Piezo1 ion channel. This mechanism may lead to improved blood flow supply and enhanced osteogenic differentiation within the femoral head.

IHGA: An interactive web server for large-scale and comprehensive discovery of genes of interest in hepatocellular carcinoma.

Mining gene expression data is valuable for discovering novel biomarkers and therapeutic targets in hepatocellular carcinoma (HCC). Although emerging data mining tools are available for pan-cancer-related gene data analysis, few tools are dedicated to HCC. Moreover, tools specifically designed for HCC have restrictions such as small data scale and limited functionality. Therefore, we developed IHGA, a new interactive web server for discovering genes of interest in HCC on a large-scale and comprehensive basis. Integrative HCC Gene Analysis (IHGA) contains over 100 independent HCC patient-derived datasets (with over 10,000 tissue samples) and more than 90 cell models. IHGA allows users to conduct a series of large-scale and comprehensive analyses and data visualizations based on gene mRNA levels, including expression comparison, correlation analysis, clinical characteristics analysis, survival analysis, immune system interaction analysis, and drug sensitivity analysis. This method notably enhanced the richness of clinical data in IHGA. Additionally, IHGA integrates artificial intelligence (AI)-assisted gene screening based on natural language models. IHGA is free, user-friendly, and can effectively reduce time spent during data collection, organization, and analysis. In conclusion, IHGA is competitive in terms of data scale, data diversity, and functionality. It effectively alleviates the obstacles caused by HCC heterogeneity to data mining work and helps advance research on the molecular mechanisms of HCC.

1-Oleate-2-palmitate-3-linoleate glycerol improves lipid metabolism and gut microbiota and decreases the level of pro-inflammatory cytokines.

Numerous studies have shown that 1-oleate-2-palmitate-3-linoleate (OPL) is the most abundant TAG in Chinese human milk, which is significantly different from human milk in other countries, where 1,3-oleate-2-palmitate (OPO) is the most abundant TAG. However, there have been few studies revealing the nutritional outcomes of OPL. Hence, the present study investigated the effects of an OPL supplementation diet on mice's nutritional outcomes, including liver lipid parameters, inflammation, lipidomes in the liver and serum, and the gut bacterial community. A high OPL (HOPL) diet decreased body weight, weight gain, liver TG, TC and LDL-C, and TNF-α, IL-1ß, and IL-6 in mice relative to low OPL (LOPL) diet. Lipidomics results showed that HOPL feeding elevated the level of anti-inflammatory lipids, such as very long-chain Cer, LPC, PC and ether TG in the liver, and serum PC, and reduced the level of oxidized lipids (liver OxTG, HexCer 18:1;2O/22:0) and serum TG. In the gut, intestinal probiotics, including Parabacteroides, Alistipes, Bacteroides, Alloprevotella and Parasutterrlla, were enriched in the HOPL-fed group. Meanwhile, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis results showed that the HOPL diet up-regulated energy metabolism and the immune system. Correlation analysis further showed that there was a relationship among the gut bacteria, lipidome profile, and nutritional outcomes. Altogether, these results indicated that an OPL-supplemented diet improved lipid metabolism and gut bacteria, reducing the level of pro-inflammatory cytokines.

Human milk phospholipid analog improved the digestion and absorption of 1,3-dioleoyl-2-palmitoyl-glycerol.

The present study investigated the effects of a human milk phospholipid analog (HPLA) on the digestion and absorption of 1,3-dioleoyl-2-palmitoyl-glycerol (OPO). The HPLA contained 26.48% phosphatidylethanolamine (PE), 24.64% phosphatidylcholine (PC), 36.19% sphingomyelin (SM), 6.35% phosphatidylinositol (PI), and 6.32% phosphatidylserine (PS), with 40.51% C16:0, 17.02% C18:0, 29.19% C18:1, and 13.26% C18:2. The HPLA prevented OPO from hydrolysis during the in vitro gastric phase, while it facilitated the digestion of OPO during the in vitro intestinal stage, resulting in the production of large amounts of diglycerides (DAGs) and monoglycerides (MAGs). In vivo experimental results showed that the HPLA might increase the gastric emptying rate of OPO and increase the hydrolysis and absorption of OPO at an early stage of intestinal digestion. Notably, fatty acids in the serum of the OPO group decreased to their initial value at 5 h, while the serum of the OPO + HPLA (OPOH) group still contained a high level of fatty acids indicating that the HPLA was helpful in maintaining serum lipid at a high level, which might be beneficial for sustainably providing energy for babies. The present study provides data support for the potential application of Chinese human milk phospholipid analogs in infant formulas.

Hypoxia-Responsive lncRNA AC115619 Encodes a Micropeptide That Suppresses m6A Modifications and Hepatocellular Carcinoma Progression.

Long noncoding RNAs (lncRNA) regulate a number of aspects of cancer biology. Recent research has shown that lncRNAs can encode micropeptides that mediate their functions in tumors. Here, we revealed that the liver-specific putative lncRNA, AC115619, is expressed at low levels in hepatocellular carcinoma (HCC) and encodes a micropeptide, designated as AC115619-22aa. AC115619 played a crucial role in the regulation of tumor progression and was a prognostic indicator in HCC. The encoded micropeptide AC115619-22aa inhibited the progression of HCC by binding to WTAP and impeding the assembly of the N6-methyladenosine (m6A) methyltransferase complex, which regulates the expression of tumor-associated genes, such as SOCS2 and ATG14. AC115619 was cotranscribed with the adjacent upstream coding gene APOB, and hypoxia induced transcriptional repression of both APOB and AC115619 by controlling HIF1A/HDAC3 and HNF4A signaling. In animal and patient-derived models, AC115619-22aa reduced global m6A levels and suppressed tumor growth. In conclusion, this study establishes AC115619 and its encoded micropeptide as potential prognostic markers and therapeutic targets for patients with HCC. SIGNIFICANCE: A micropeptide encoded by lncRNA AC115619 impedes formation of the m6A methylation complex to lower m6A levels and reduce the growth of hepatocellular carcinoma.

Comprehensive quality evaluation of plant-based cheese analogues.

BACKGROUND: In recent years, there has been an increasing demand for plant-based cheese analogues, however, the protein content of plant-based cheeses currently on the market is generally low and cannot meet the nutritional needs of consumers. RESULTS: Based on the ideal value similarity method (TOPSIS) analysis the best recipe for plant-based cheese was 15% tapioca starch, 20% soy protein isolate, 7% gelatine as a quality enhancer and 15% coconut oil. The protein content of this plant-based cheese was170.1 g kg-1 , which was close to commercial dairy-based cheese and significantly higher than commercial plant-based cheese, The fat content was 114.7 g kg-1 , lower than that of commercial dairy-based cheese. The rheology properties show that the viscoelasticity of the plant-based cheese is higher than that of dairy-based cheese and commercial plant-based. The microstructure results show that the type and content of protein has a significant impact on its microstructure. The Fourier-transform infrared (FTIR) spectrum of the microstructure shows a characteristic value at 1700 cm-1 , because the starch was heated and leached to form a complex with lauric acid under the action of hydrogen bond. It can be inferred that in the interaction between plant-based cheese raw materials, fatty acids serve as a bridge between starch and protein. COUCLUSION: This study described the formula of plant-based cheese and the interaction mechanism between the ingredients, providing a basis for the development of subsequent plant-based cheese related products. © 2023 Society of Chemical Industry.

Effects of various thermal treatments on interfacial composition and physical properties of bovine milk fat globules.

This study aimed to investigate changes of milk fat globules (MFG) and their membranes after thermal treatments, and further analyzed the relationship between the stability of MFG and interfacial compositions of milk fat globule membrane (MFGM). We characterized the influence of three kinds of thermal treatments on fat globule interfacial components (including interfacial phospholipids and interfacial protein) and physical properties using phospholipidomics and several microscopy techniques. The results showed that size of MFG increased from 2.96 µm to 3.59 µm and ζ-potential decreased from -9.71 mV to -13.23 mV after thermal treatment, suggesting that MFGM was damaged and MFG occurred coalescence. Thermal treatment increased the Young's modulus of MFGM and made membranes more fragile. The abundance of MFGM proteins decreased while casein and ß-lactoglobulin increased after thermal treatment. Results of phospholipidomics showed that 27 phospholipid species could be used to distinguish the samples. Pasteurization reduced mainly SM and PC located in the outer bilayer of MFGM, while ultra-pasteurization reduced not only SM and PC but also PI and PE located in the inner leaflet. Based on correlation analysis, the increase in Young's modulus of MFGM during thermal treatment might be related to changes in chemical components on the membrane, suggesting a potential link between the change of MFGM components and fat globule coalescence behavior.