Search Results (270)

Thermodynamic simulations of fluid–rock interactions provide valuable insights into mineral deposit formation mechanisms. This study investigates the Pulang porphyry Cu-Au deposit in the Sanjiang Tethys Orogen, employing both Gibbs energy minimization (GEM) and the Law of mass action (LMA) method to understand alteration overprinting and metal precipitation. The modeling results suggest that the ore-forming fluid related to potassic alteration was initially oxidized (ΔFMQ = +3.54~+3.26) with a near-neutral pH (pH = 5.0~7.0). Continued fluid–rock interactions, combined with the input of reduced groundwater, resulted in a decrease in both pH (4.8~6.1) and redox potential (ΔFMQ~+1), leading to the precipitation of propylitic alteration minerals and pyrrhotite. As temperature further decreased, fluids associated with phyllic alteration showed a slight increase in pH (5.8~6.0) and redox potential (ΔFMQ = +2). The intense superposition of propylitic and phyllic alteration on the potassic alteration zone is attributed to the rapid temperature decline in the magmatic–hydrothermal system, triggering fluid collapse and reflux. Mo, mainly transported as HMoO₄⁻ and MoO₄⁻², precipitated in the high-temperature range; Cu, carried primarily by CuCl complexes (CuCl₄⁻³, CuCl₂⁻, CuCl), precipitated over intermediate to high temperatures; and Au, transported as Au-S complexes (Au(HS)₂⁻, AuHS), precipitated from intermediate to low temperatures. This study demonstrates that fluid–rock interactions alone can account for the observed sequence of alteration and mineralization in porphyry systems. Full article

Human milk oligosaccharides (HMOs) have garnered significant attention as one of the bioactive components in human milk, with growing applications in infant formula and food products. HMOs enhance butyrate production, which is produced by butyrate-producing bacteria such as Faecalibacterium prausnitzii and contributes to gut health through its diverse biological functions. However, the specific mechanisms by which individual HMOs promote butyrate production remain unclear. In this study, we conducted in vitro co-culture experiments of F. prausnitzii and Bifidobacterium bifidum, examining their relative abundance, fatty acid production, residual sugar levels, and gene expression. Our results revealed that B. bifidum utilizes HMOs and provides the constituent sugars to F. prausnitzii, thereby promoting butyrate production by F. prausnitzii. Furthermore, we found that the underlying mechanisms vary depending on the structure of the HMOs. Specifically, 2′-fucosyllactose and 3′-sialyllactose enhance the butyrate production efficiency of F. prausnitzii, while 6′-sialyllactose primarily promotes the growth of F. prausnitzii. These findings not only deepen our understanding of how HMOs influence infant gut health but also suggest new directions for developing nutritional products that leverage the distinct functional properties of each HMO. Full article

Background/Objectives: Early childhood is a critical window of development, which is influenced by early life exposures including breastfeeding. Observational and preclinical studies have linked human milk oligosaccharides (HMOs) with neurocognitive development. However, less attention has focused on behavioral outcomes including temperament and eating behaviors. Herein, we investigated the associations between HMO consumption and child temperament and child eating behaviors through four years of age. Methods: Participants were drawn from the STRONG Kids 2 cohort. Human milk was collected at 6 weeks postpartum, and HMO relative abundances were determined by HPLC-MS. Using validated questionnaires, child temperament was assessed at 3, 18, and 48 months of age, and child eating behaviors were measured at 12, 18, 24, 36, and 48 months of age. After adjusting for covariates, multiple linear regressions were carried out to assess the relationship between HMOs and the outcome measures. Results: The HMO profile of mothers showed two distinct clusters explained by maternal secretor status. Significant associations between HMO and surgency were only found in the full cohort and secretors, while more associations between HMO and negative affectivity were observed in non-secretors. A significant number of associations was observed between HMOs and child eating behaviors in full cohort, secretors, and non-secretors. HMO diversity, total fucosylation, and total sialylation were positively associated with food responsiveness, while neutral HMOs presented negative associations. However, these associations with food responsiveness were not observed in non-secretors. Conclusions: HMO profiles were associated with behavioral outcomes in the children, with variations by child age and maternal secretor status, highlighting the potential role of HMOs within the broader context of maternal and postnatal influences. Full article

Background and Objectives: Breast reconstruction following mastectomy improves quality of life and psychosocial outcomes, yet it is not consistently performed despite multiple federal mandates. Current data shows decreased reconstruction in minority races, those with a low socioeconomic status, and those holding public health insurance. Many barriers remain misunderstood or unstudied. This study examines barriers to post-mastectomy breast reconstruction to promote a supportive clinical climate by addressing multifactorial obstacles to equitable access to care. Materials and Methods: The California Cancer Registry Data Surveillance, Epidemiology, and End Results (SEER) database and California Health and Human Services Agency Cancer Surgeries Database (2013–2021 and 2000–2021, respectively) were used in this retrospective observational study on mastectomy with immediate breast reconstruction (IBR), delayed breast reconstruction (DBR), or mastectomy only (MO) rates. Data were collected on age, sex, race, insurance type, hospital type, socioeconomic status, and residence. Pearson’s chi-square analysis was performed. Results: We found that 168,494 mastectomy and reconstruction surgeries were performed (82.36% MO, 7% IBR, 10.6% DBR). The 40–49 age group received significantly less MO (38.1%) compared to the 70–74 age group (94.8%, (p = <0.001). Significantly more reconstruction was carried out in patients with private, HMO, or PPO insurance (IBR 75.86%, DBR 75.32%, p = <0.001). Almost all breast surgeries were in urban areas as opposed to rural/isolated rural areas (96.02% vs. 1.55%, p = <0.001). There was no significant difference between races. Of all surgeries, 7.46% were completed in a cancer center with significantly higher rates of IBR. LA County, San Luis Obispo/Ventura County, and Northern CA had significantly more MO than other regions (p = <0.001). Conclusions: Reconstruction rates after mastectomy are low, with only 17.64% of patients undergoing reconstruction. Nationally, 70.5% of patients received MO, with 29.6% undergoing reconstruction. Significant factors positively contributing to reconstruction were private insurance, high SES, cancer center care, and urban residency. Identified barriers include public health insurance enrollment, rural or non-urban residence, older age, low SES, and non-white race/ethnicity, indicating potential monetary influences on care. Full article

Background: Human milk oligosaccharides (HMOs) serve as critical bioactive components supporting infant growth and development. However, the influence of maternal metabolic factors during lactation on HMOs remains to be fully elucidated. This study aimed to investigate the association between maternal metabolic factors and HMOs, as well as the potential mediating effects of these factors. Methods: An observational cross-sectional study was conducted in Central South China, enrolling 196 lactating mothers. HMOs were quantified using liquid chromatography-tandem mass spectrometry. Maternal metabolic factors were assessed through physical examinations. Associations between metabolic factors and HMOs were analyzed using linear regression, and mediation effects were evaluated. Results: HMOs from Central South China were predominantly composed of neutral fucosylated HMOs. Significant differences were observed in the levels of several HMOs across maternal age groups and lactation periods. The concentration of 3′-sialyllactose (3′-SL) exhibited a negative association with the pre-pregnancy body mass index (BMI) (β = −0.16, 95% CI: −0.29, −0.03; p = 0.02), while a positive association was found with maternal heart rate (β = 0.14, 95% CI: 0.01, 0.27; p = 0.04). However, these associations were different between secretor and non-secretor mothers. Associations of 3′-SL with pre-pregnancy BMI and maternal HR were only found in the secretor mothers. Triglycerides and low-density lipoprotein cholesterol mediated the associations between maternal pre-pregnancy BMI and 3′-sialyllactose (3′-SL). Conclusions: The variations of several HMOs among mothers from Central South China were associated with maternal age and lactation period. The concentration of 3′-SL was negatively correlated with maternal pre-pregnancy BMI. The potential mechanism underlying the influence of maternal BMI on 3′-SL levels may involve maternal lipid metabolism and genetic factors. Full article

Abscesses are among the diseases affecting the survival of captive musk deer and are difficult to identify in their early stages. In this study, metagenomic sequencing, 16S rRNA sequencing, and paraffin sectioning were used to analyze the microbiota in the abscess musk deer pus group (AMP), abscess musk deer oral group (AMO), and healthy musk deer oral group (HMO) to compare the differences in microbiota in musk deer. By detecting differences in the oral microbiota through throat swabs, we aimed to monitor the early onset of abscess disease to facilitate timely intervention and treatment. The results showed that the alpha diversity of HMO microbiota was significantly higher than that of the AMP and AMO samples. Beta diversity results indicated that there were significant differences in the bacterial communities of HMO and AMO samples, and no significant difference was found between AMO and AMP samples. A taxonomic analysis of the bacterial species indicated that differences between HMO and AMP groups were found in the Fusobacterium and Trueperella species. Fusobacterium and Trueperella were the main pathogenic bacteria responsible for the occurrence of abscess diseases in forest musk deer in this study. Furthermore, the appearance of Fusobacterium and Trueperella in the oral cavity can serve as biomarkers for the early diagnosis of abscess disease in musk deer. Full article

The Saccharomyces cerevisiae chromosomal architectural protein Hmo1 is categorized as an HMGB protein, as it contains two HMGB motifs that bind DNA in a structure-specific manner. However, Hmo1 has a basic C-terminal domain (CTD) that promotes DNA bending instead of an acidic one found in a canonical HMGB protein. Hmo1 has diverse functions in genome maintenance and gene regulation. It is implicated in DNA damage tolerance (DDT) that enables DNA replication to bypass lesions on the template. Hmo1 is believed to direct DNA lesions to the error-free template switching (TS) pathway of DDT and to aid in the formation of the key TS intermediate sister chromatid junction (SCJ), but the underlying mechanisms have yet to be resolved. In this work, we used genetic and molecular biology approaches to further investigate the role of Hmo1 in DDT. We found extensive functional interactions of Hmo1 with components of the genome integrity network in cellular response to the genotoxin methyl methanesulfonate (MMS), implicating Hmo1 in the execution or regulation of homology-directed DNA repair, replication-coupled chromatin assembly, and the DNA damage checkpoint. Notably, our data pointed to a role for Hmo1 in directing SCJ to the nuclease-mediated resolution pathway instead of the helicase/topoisomerase mediated dissolution pathway for processing/removal. They also suggested that Hmo1 modulates both the recycling of parental histones and the deposition of newly synthesized histones on nascent DNA at the replication fork to ensure proper chromatin formation. We found evidence that Hmo1 counteracts the function of histone H2A variant H2A.Z (Htz1 in yeast) in DDT possibly due to their opposing effects on DNA resection. We showed that Hmo1 promotes DNA negative supercoiling as a proxy of chromatin structure and MMS-induced DNA damage checkpoint signaling, which is independent of the CTD of Hmo1. Moreover, we obtained evidence indicating that whether the CTD of Hmo1 contributes to its function in DDT is dependent on the host’s genetic background. Taken together, our findings demonstrated that Hmo1 can contribute to, or regulate, multiple processes of DDT via different mechanisms. Full article

The issue of antibiotic-resistant bacterial infections, coupled with the rise in viral pandemics and the slow development of new antibacterial and antiviral treatments, underscores the critical need for novel strategies to mitigate the spread of drug-resistant pathogens, enhance the efficacy of existing therapies, and accelerate the discovery and deployment of innovative antimicrobial and antiviral solutions. One promising approach to address these challenges is the dietary supplementation of non-digestible oligosaccharides (NDOs). NDOs, including human milk oligosaccharides (HMOs), play a vital role in shaping and sustaining a healthy gut microbiota. Beyond stimulating the growth and activity of beneficial gut bacteria, NDOs can also interact directly with pathogenic bacteria and viruses. Their antiviral and antibacterial properties arise from their unique interactions with pathogens and their ability to modulate the host’s immune system. NDOs can function as decoy receptors, inhibit pathogen growth, bind to bacterial toxins, stimulate the host immune response, exhibit anti-biofilm properties, and enhance barrier protection. However, a notable gap exists in the comprehensive assessment of in vivo and clinical data on this topic. This review aims to provide an in-depth overview of the in vivo evidence related to the antiviral and antibacterial effects of various NDOs and HMOs, with a focus on discussing their possible mechanisms of action. Full article

Human milk (HM) provides maximum health benefits for infants. This is due in part to the activity of its minor components, including HM proteins and oligosaccharides (HMOs). Where HM is unavailable, infant formulas (IFs) are normally used, the two most common types being cow milk- and goat milk-based formulas (CIF and GIF). The aim of this study was to compare the antioxidant properties of HM, CIF and GIF, together with those of their respective oligosaccharides (HMOs, CMOs and GMOs), using in vitro model systems. The ability of these oligosaccharides to attenuate inflammation (expression of IL-1α, TNFα, IL-6 and IL-8) was also assessed using a U937 cell culture model. Results showed that GIF and GMOs exhibited the highest antioxidant potential. The iron-reducing and iron-chelating properties of both IFs were comparable to those for HM, while the iron-chelating ability of the CMOs was lowest. None of the oligosaccharides significantly reduced U937 cytokine expression following induction of inflammation; however, GMOs consistently reduced expression of IL-1α, TNFα and IL-6 to a greater extent than the other oligosaccharides, presumably by competitive binding to immune receptors. In conclusion, GMOs have a greater antioxidant potential than CMOs and may have some inflammation-attenuating ability as well. Full article

Breast milk is rich in bioactive components, especially human milk oligosaccharides (HMOs), which are crucial for establishing gut microbiota. The 2′-FL (2-Fucosyllactose), one of the most abundant oligosaccharides in breast milk, functions as a selective prebiotic. Objective: To examine the effect of adding 2′-FL (2-Fucosyllactose) to an infant formula containing prebiotic galacto-oligosaccharides (GOSs) and fructo-oligosaccharides (FOSs) on the gut microbiome of healthy formula-fed infants. Methods: This study enrolled infants from three groups: an HMO experimental group (n = 29), a GOS/FOS control group (n = 30), and an exclusively breastfed (breast milk [BM]) reference group (n = 28). Fecal samples from the three groups in the first and fourth months of life were analyzed. The V3 and V4 regions of the 16S rRNA gene were amplified and sequenced on the Illumina MiSeq. ANOVA, Kruskal–Wallis, richness indices (Chao1, Shannon), UniFrac distances, and the Adonis tests were used to perform statistical analyses on the relative abundance of phyla and genera, as well as the alpha and beta-diversity of the gut microbiota. Results: After intervention, Actinobacteriota emerged as the predominant phylum in both the HMO (60.4%) and BM (46.6%) groups. Bifidobacterium and Escherichia-Shigella were identified as the two most abundant bacterial genera in both groups. Nevertheless, the statistical analysis showed that the relative abundance of Bifidobacterium in the HMO formula-fed group after intervention was similar to that in the BM group (p > 0.05). Infants in the HMO and GOS/FOS groups showed higher relative abundance of [Ruminococcus]_gnavus_group bacteria compared to those in the BM group. Groups fed with infant formula demonstrated higher alpha-diversity of gut microbiota compared to breastfed infants (p < 0.05), at the time of admission as well as after the intervention. Beta-diversity was significantly different among the three groups, according to type of feeding. Infants fed a 2′-FL-supplemented infant formula exhibited growth comparable to that of breastfed infants throughout the intervention period, demonstrating that the formula was both safe and well tolerated. Conclusions: Adding 2′-FL to an infant formula containing 4 g/L of GOS + FOS resulted in a stronger bifidogenic effect compared to the formula without 2′-FL. Full article

Background/Objectives: Individuals with HIV on combined antiretroviral therapy (ART) with virologic suppression exhibit chronic immune activation and immune dysfunction. Numerous studies have shown that human milk oligosaccharide (HMO) controls the postnatal transmission of HIV-1, but its effect on adult HIV-1 infection is not known. The purpose of this study was to investigate the anti-HIV activity of Lacto-N-fucopentaose III (LNFPIII) in adult blood-borne macrophages. Methods: Primary human monocyte-derived macrophages from the blood of HIV-seronegative individuals were infected with HIV and treated with or without dextran-conjugated LNFPIII (P3DEX). HIV replication was measured by quantifying the accumulation of HIV Gag p24 in the culture supernatants by ELISA. The quantities of chemokines MIP-1α, MIP-1β, and CCL5 in the culture supernatant were also measured by ELISA. The expression of IL-1β, IL-18, TNFα, IL-10, BECN1, and housekeeping gene HuPO in the macrophages was determined by qRT PCR. The expression of NF-kB, LC3, p62, and β-actin was measured by immunoblotting. Results: We found that P3DEX controls HIV replication without affecting HIV binding and/or internalization by human macrophages. The treatment of HIV-infected macrophages with P3DEX increased the quantity of beta (β)-chemokines MIP-1α, CCL5, and MIP-1β, which are known to have anti-HIV activity. Furthermore, the treatment of HIV-infected macrophages with P3DEX increased autophagic flux in a TLR8-dependent manner and ameliorated the expression of proinflammatory cytokines. These results suggest that P3DEX is a prominent milk-derived sugar that simultaneously augments anti-viral mechanisms and controls immune activation. These findings prudently justify the use and clinical development of P3DEX as a host-directed therapeutic option for people living with HIV. Full article

Background: Preventing neurodevelopmental impairment after extremely preterm birth remains challenging. While breast milk feeding is linked to better neurodevelopment, the underlying mechanisms are unclear. This study explored the association between individual human milk oligosaccharides (HMO) and neurodevelopment at two years of age in extremely preterm children. Methods: Milk samples from mothers of 76 extremely preterm infants collected at two weeks after birth were analyzed for 15 dominant HMOs. Register data from examination and Bayley-III neurodevelopmental assessment at two years’ corrected age was retrieved and categorized into levels of impairment. An exploratory analysis examined associations between the HMO composition and neurodevelopment. Results: Bioinformatic volcano plots revealed associations between specific HMOs and outcomes: 3FL with less neurodevelopmental impairment, LSTb with higher Bayley-III cognitive scores, and LSTa with worse neurodevelopmental impairment outcomes. Spearman correlations indicated LSTa was linked to more neurodevelopmental impairment (p = 0.018), lower language (p = 0.009), and motor (p = 0.02) scores, whereas 3FL correlated with less neurodevelopmental impairment (p = 0.02). Dichotomized analysis showed LSTa was associated with more neurodevelopmental impairment and lower language scores (p < 0.05), 3FL with milder neurodevelopmental impairment (p < 0.05), and LSTb with better cognitive (p < 0.01) and language (p < 0.05) scores. No significant associations were found for HMO diversity, total sialic acid content, or secretor/Lewis patterns. Conclusions: In this explorative hypothesis-generating study, certain HMOs appeared to be associated with both potentially beneficial and adverse neurodevelopmental outcomes in extremely preterm infants. However, these findings should be interpreted with caution, as they do not constitute evidence but rather serve as a preliminary foundation for future hypothesis-driven research. Full article

Background: This descriptive study aimed to assess the survival rates and outcomes of dental implants in one of the four national HMOs in Israel. Data are provided for the period from 1 January 2014 to 31 December 2022. Materials and Methods: This retrospective analysis utilized electronic medical records of patients who underwent dental implant placement during the specified period. Statistical analyses included chi-squared tests, Student’s t-tests, and generalized estimating equation (GEE) analyses to identify potential risk factors associated with early and late implant failures. Results: A total of 158,824 dental implants were placed in 53,874 patients. The overall implant failure rate was 2.21%, while the early failure rate during the osseointegration phase—before prosthetic reconstruction—was 1.56%. Significant associations with implant failure were observed for male patients (2.53% failure rate), implants in the maxillary molar region (3%), and the central incisor region (3.37%), approximately double the failure rates seen in other implant sites (p < 0.001). Conclusions: This extensive data analysis demonstrates a low overall failure rate for dental implants. The highest failure incidence occurred within the first year post-implantation, declining in subsequent years irrespective of rehabilitation status. Early failure risk factors differ based on various factors and should be carefully integrated into presurgical planning. Full article

Background: While previous studies have shown that occupational choices are influenced by traditional gender perceptions, little is known about gender’s role in choosing self-employment among family physicians. Family medicine, with its emphasis on holistic and integrative attitudes that align with independent practice characteristics, presents a unique context for examining gender-related decisions in choosing self-employment. Objectives: To examine the role of gender in family physicians’ transition to self-employed practice, focusing on gender differences in motivations and considerations for this career choice, and to analyze how traditional gender roles manifest in professional decision-making among highly educated medical professionals. Methods: A qualitative study based on in-depth interviews was conducted with 27 self-employed family physicians in Israel who recently chose to start independent practice rather than remaining salaried physicians in Health Maintenance Organizations (HMOs). Interviews were analyzed using thematic content analysis with a gender-sensitive approach. Results: Despite their advanced education and professional status, female family physicians tended to maintain traditional gender patterns in their professional choices. Women emphasized work–family flexibility as a primary consideration and expressed less confidence in financial management self-efficacy, often delegating these responsibilities to their spouses. In contrast, male family physicians displayed traditionally “feminine” characteristics in their professional approach, including emphasis on holistic care and family involvement. Male physicians also cited work–life balance and the opportunity for a more comprehensive, biopsychosocial approach to patient care as key factors in choosing family medicine and self-employment. Conclusions: The findings demonstrate the complexity of gender roles in family physicians’ professional choices, revealing both persistence of traditional gender roles among women and different patterns among men. While male physicians displayed characteristics traditionally identified as feminine, these patterns may reflect both gender role evolution and generational shifts towards work–family integration and collaborative patient care. This study highlights how gender and generational factors shape career decisions in primary care, with implications for medical education and healthcare organization policies. Full article

The purpose of this study was to investigate the degradation mechanism of Bifidobacterium on breast milk oligosaccharides (HMOs) and its application in infant nutrition. The composition and characteristics of HMOs were introduced, and the degradation mechanism of HMOs by Bifidobacterium was described, including intracellular and extracellular digestion and species-specific differences. The interaction between Bifidobacterium and Bacteroides in the process of degrading HMOs and its effect on intestinal microecology were analyzed. The effects of HMO formula milk powder on the intestinal microbiota of infants were discussed, including simulating breast milk composition, regulating intestinal flora and immune function, infection prevention, and brain development. Finally, the research results are summarized, and future research directions are proposed to provide directions for research in the field of infant nutrition. Full article