Heat-killed Prevotella intermedia promotes the progression of oral squamous cell carcinoma by inhibiting the expression of tumor suppressors and affecting the tumor microenvironment.

BACKGROUND: Oral microbial dysbiosis contributes to the development of oral squamous cell carcinoma (OSCC). Our previous study showed that Prevotella intermedia (P. intermedia) were enriched in the oral mucosal surface, plaque, and saliva of patients with OSCC. Intratumoral microbiome could reshape the immune system and influence the development of various tumors. However, the invasion status of human OSCC tissues by P. intermedia and the pathway through which intratumoral P. intermedia potentiates tumor progression remain unexplored. METHODS: P. intermedia in human OSCC or normal tissues was detected by FISH. A mouse OSCC cell line SCC7 was adopted to investigate the effects of heat-killed P. intermedia treatment on cell proliferation, invasion, and cytokine release by using CCK-8 assay, transwell invasion assay and ELISA. Moreover, we established a mouse transplanted tumor model by using SCC7 cells, injected heat-killed P. intermedia into tumor tissues, and investigated the effects of heat-killed P. intermedia on tumor growth, invasion, cytokine levels, immune cell infiltrations, and expression levels by using gross observation, H&E staining, ELISA, immunohistochemistry, mRNA sequencing, and transcriptomic analysis. RESULTS: Our results indicated that P. intermedia were abundant in OSCC and surrounding muscle tissues. Heat-killed P. intermedia promoted SCC7 cell proliferation, invasion and proinflammatory cytokine secretions, accelerated transplanted tumor growth in mice, exacerbate muscle and perineural invasion of OSCC, elevated the serum levels of IL-17A, IL-6, TNF-α, IFN-γ, and PD-L1, induced Treg cells M2 type macrophages in mouse transplanted tumors. The data of transcriptomic analysis revealed that heat-killed P. intermedia increased the expression levels of inflammatory cytokines and chemokines while reduced the expression levels of some tumor suppressor genes in mouse transplanted tumors. Additionally, IL-17 signaling pathway was upregulated whereas GABAergic system was downregulated by heat-killed P. intermedia treatment. CONCLUSIONS: Taken together, our results suggest that P. intermedia could inhibit the expression of tumor suppressors, alter the tumor microenvironment, and promote the progression of OSCC.

Disaggregation of Breastfeeding Initiation Rates by Race and Ethnicity - United States, 2020-2021.

Introduction: Although breastfeeding is the ideal source of nutrition for most infants, racial and ethnic disparities exist in its initiation. Surveillance rates based on aggregated data can challenge the understanding and monitoring of effective, culturally appropriate interventions among racial and ethnic subgroups. Aggregated data have historically estimated breastfeeding rates among a few large racial and ethnic groups. We examined differences in breastfeeding initiation rates by disaggregation of data to finer subgroups of race and ethnicity. Methods: We analyzed births from January 1, 2020, through December 31, 2021, in 48 states and the District of Columbia by using National Vital Statistics System birth certificate data. Data indicate whether an infant received any breast milk during birth hospitalization and include self-reported maternal race and ethnicity. Cross-tabulations of race and ethnicity by breastfeeding initiation were calculated and compared across aggregated and disaggregated categories. Results: The overall prevalence of breastfeeding initiation was 84.0%, ranging from 74.5% (mothers identifying as Black) to 94.0% (mothers identifying as Japanese). The aggregated prevalence of breastfeeding initiation among mothers identifying as Hispanic was 86.8%; disaggregated estimates by Hispanic origin ranged from 82.2% (Puerto Rican) to 90.9% (Cuban). Conclusion: Substantial variation in the prevalence of breastfeeding initiation across disaggregated racial or ethnic categories exists. Disaggregation of racial and ethnic data unmasked differences that could reflect variations in cultural practices or systemic barriers to breastfeeding. Understanding why these differences exist could guide public health practitioners' efforts to improve and tailor breastfeeding support.

Attenuation of NLRP3 Inflammasome by Cigarette Smoke is Correlated with Decreased Defense Response of Oral Epithelial Cells to Candida albicans.

BACKGROUND: It is well recognized that both smoke and Candida infection are crucial risk factors for oral mucosal diseases. The nucleotide-binding domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome and its downstream effectors, interleukin (IL)-1ß and IL-18, are pivotal to the host defense against Candida and other pathogens. METHODS: The present study was designed to explore the effects of cigarette smoke and C. albicans on the NLRP3 inflammasome and its downstream signal pathway via in vitro cell model. Oral epithelial cells (Leuk-1 cells) were exposed to cigarette smoke extract (CSE) for 3 days and/or challenged with C. albicans. RESULTS: Microscopically, Leuk-1 cells exerted a defense response to C. albicans by markedly limiting the formation of germ tubes and microcolonies. CSE clearly eliminated the defense response of Leuk-1 cells. Functionally, CSE repressed NLRP3 inflammasome, and IL-1ß and IL-18 activation induced by C. albicans in Leuk-1 cells. CONCLUSION: Our results suggested that in oral epithelial cells, the NLRP3 inflammasome might be one of the target pathways by which CSE attenuates innate immunity and leads to oral disorders.

Public Belief in the Maternal Health Benefits of Breastfeeding - United States, 2018 and 2021.

The objective of this study was to better understand US public awareness of maternal health benefits of breastfeeding. Data from the 2018 and 2021 SummerStyles surveys were analyzed to explore public belief in select maternal benefits of breastfeeding. As in 2018, in 2021 a low percentage of respondents believed that breastfeeding protects the mother against breast cancer (23.9%), high blood pressure (15.5%), or type 2 diabetes (15.4%), with male, older, and unmarried respondents less likely to believe in these protective effects. More public awareness of maternal benefits of breastfeeding might help increase demand for breastfeeding-supportive programs and policies.

Early introduction of complementary foods/drinks and milk feeding type in the Special Supplemental Nutrition Program for Women, Infants and Children (WIC).

Infants younger than 4 months are not ready for complementary foods/drinks (any solid or liquid other than breast milk or infant formula). Almost half of US infants participate in the Special Supplemental Nutrition Program for Women, Infants and Children (WIC), which provides nutrition education and support to low-income families. We describe the prevalence of early introduction (<4 months) of complementary foods/drinks and examine the association of milk feeding type (fully breastfed, partially breastfed or fully formula fed) with early introduction of complementary foods/drinks. We used data from 3310 families in the longitudinal WIC Infant and Toddler Feeding Practices Study-2. We described the prevalence of early introduction of complementary foods/drinks and modeled the association of milk feeding type at Month 1 with early introduction of complementary foods/drinks using multi-variable logistic regression. Thirty-eight percent of infants were introduced early to complementary foods/drinks (<4 months). In adjusted models, infants who were fully formula fed or partially breastfed at Month 1 were 75% and 57%, respectively, more likely to be introduced early to complementary foods/drinks compared with fully breastfed infants. Almost two in five infants were given complementary foods/drinks early. Formula feeding at Month 1 was associated with higher odds of early introduction of complementary foods/drinks. There are opportunities to support families participating in WIC to prevent early introduction of complementary foods/drinks and promote child health.

Timing of Introduction of Complementary Foods - United States, 2016-2018.

The American Academy of Pediatrics (AAP) recommends introducing complementary foods (i.e., any solid or liquid other than breast milk or infant formula) to infants at approximately age 6 months (1). Although a consensus on ideal timing is lacking, most experts agree that introduction of complementary foods before age 4 months is too early because of infant gastrointestinal and motor immaturity (1,2). In addition, early introduction prevents exclusively breastfed infants from reaching the recommended 6 months of exclusive breastfeeding (1) and might be associated with increased risk for overweight and obesity (3). Nationally representative data on complementary feeding are limited; state-level estimates have been previously unavailable. CDC analyzed 2016-2018 data from the National Survey of Children's Health (NSCH) (N = 23,743) to describe timing of complementary feeding introduction and prevalence of early introduction of complementary foods before age 4 months (early introduction) among children aged 1-5 years. Prevalence of early introduction was 15.6% nationally and varied geographically and across sociodemographic and infant feeding characteristics. These estimates suggest that approximately one in six infants are introduced to complementary foods before they are developmentally ready. Efforts by health care providers and others who might influence infant feeding practices could help decrease the number of infants who are introduced to complementary foods too early.

[Research and Development Trend of Medical Oxygen Production Equipment].

Oxygen therapy is an effective clinical method for the treatment of respiratory disorders, oxygen concentrator as a necessary medical auxiliary equipment in hospitals, its research and development has been a hot spot. The study reviewed the development history of the ventilator, introduced the two preparation technique of the oxygen generator pressure swing absorption (PSA) and vacuum pressure swing adsorption (VPSA), and analyzed the core technology development of the oxygen generator. In addition, the study compared some major brands of oxygen concentrators on the market and prospected the development trend of oxygen concentrators.

Impacts of human pressure and climate on biodiversity-multifunctionality relationships on the Qinghai-Tibetan Plateau.

Many studies have investigated the effects of environmental context on biodiversity or multifunctionality in alpine regions, but it is uncertain how human pressure and climate may affect their relationships. Here, we combined the comparative map profile method with multivariate datasets to assess the spatial pattern of ecosystem multifunctionality and further identify the effects of human pressure and climate on the spatial distribution of biodiversity-multifunctionality relationships in alpine ecosystems of the Qinghai-Tibetan Plateau (QTP). Our results indicate that at least 93% of the areas in the study region show a positive correlation between biodiversity and ecosystem multifunctionality across the QTP. Biodiversity-multifunctionality relationships with increasing human pressure show a decreasing trend in the forest, alpine meadow, and alpine steppe ecosystems, while an opposite pattern was found in the alpine desert steppe ecosystem. More importantly, aridity significantly strengthened the synergistic relationship between biodiversity and ecosystem multifunctionality in forest and alpine meadow ecosystems. Taken together, our results provide insights into the importance of protecting and maintaining biodiversity and ecosystem multifunctionality in response to climate change and human pressure in the alpine region.

Associations Between Breastfeeding and Post-perinatal Infant Deaths in the U.S.

INTRODUCTION: Initiation of breastfeeding has been associated with reduced post-perinatal infant mortality. Although most states have initiatives to protect, promote, and support breastfeeding, no analysis of the association between breastfeeding and infant mortality has been conducted at the state and regional levels. To understand the associations between breastfeeding and post-perinatal infant mortality, the initiation of breastfeeding with post-perinatal infant mortality was analyzed by geographic region and individual states within each region. METHODS: This study was a prospective cohort analysis linking U.S. national birth and post-perinatal infant death data for nearly 10 million infants born in 2016-2018, who were then followed for one year after birth and analyzed in 2021-2022. RESULTS: A total of 9,711,567 live births and 20,632 post-perinatal infant deaths from 48 states and the District of Columbia were included in the analysis. The overall AOR and 95% CIs for breastfeeding initiation with post-perinatal infant mortality was 0.67 (0.65, 0.69, p<0.0001) for days 7-364. All seven U.S. geographic regions had significant reductions in postperinatal infant deaths associated with breastfeeding initiation; Mid-Atlantic and Northeast regions had the largest reductions with AOR of 0.56 (95% CI=0.51, 0.61, p<0.001 and 0.50, 0.63, p<0.001, respectively), whereas the Southeast had the smallest reduction with AOR of 0.79 (95% CI=0.75, 0.84, p<0.001). Statistically significant results were noted for 35 individual states for reduction in total post-perinatal infant deaths. CONCLUSIONS: Although regional and state variation in the magnitude of the association between breastfeeding and infant mortality exists, the consistency of reduced risk, together with existing literature, suggests that breastfeeding promotion and support may be a strategy to reduce infant mortality in the U.S.

Oral squamous cell carcinoma-derived EVs promote tumor progression by regulating inflammatory cytokines and the IL-17A-induced signaling pathway.

BACKGROUND: Inflammatory cytokines in the tumor microenvironment (TME) contribute to tumor growth, proliferation, and invasion, and tumor-derived extracellular vesicles (EVs) act as critical "messengers" of communication in the tumor microenvironment. The effects of EVs derived from oral squamous cell carcinoma (OSCC) cells on tumor progression and the inflammatory microenvironment are still unclear. Our study aims to investigate the role of OSCC-derived EVs in tumor progression, the imbalanced TME, and immunosuppression and their effect on the IL-17A-induced signaling pathway. METHODS: EVs were isolated from the supernatant of a mouse OSCC cell line, SCC7. The effects of SCC7-EVs and the EV release-specific inhibitor GW4869 on the proliferation and migration of SCC7 cells were investigated in vitro by using CCK-8 and scratch wound healing assays. RT-qPCR and ELISA were performed to examine the alterations in cytokine levels. Then, a mouse xenograft model of OSCC was established by submucosal injection of SCC7 cells with or without SCC7-EV and GW4869 treatment. The effects of GW4869 and SCC7-EVs on xenograft tumor proliferation and invasion were investigated by tumor volume determination and histopathological examination. ELISA was used to investigate the changes in serum cytokine levels. Immunohistochemistry was adopted to analyze the alterations in the levels of inflammatory cytokines, immune factors, and crucial molecules in the IL-17A signaling pathway. RESULTS: SCC7-derived EVs increased the supernatant and serum levels of IL-17A, IL-10, IL-1ß, and PD-L1, while GW4869 decreased those of TNF-α and IFN-γ. SCC7-EV treatment significantly increased xenograft tumor growth and invasion in mice but resulted in little liquefactive necrosis in tumors. However, GW4869 treatment significantly inhibited xenograft tumor growth but resulted in more liquefactive necrosis. SCC7-derived EVs decreased the expression level of PTPN2, suppressing the immune responses of CD8 + T cells in vivo. Moreover, SCC7-EV treatment significantly enhanced the tumor expression levels of crucial molecules in the IL-17A pathway, including IL-17A, TRAF6 and c-FOS, whereas GW4869 treatment significantly reduced those levels in tumor tissues. CONCLUSION: Our results indicated that OSCC-derived EVs can promote tumor progression by altering the TME, causing an inflammatory cytokine imbalance, inducing immunosuppression, and contributing to overactivation of the IL-17A-induced signaling pathway. Our study might provide novel insights into the role of OSCC-derived EVs in tumor biological behavior and immune dysregulation.

Sono-Driven STING Activation using Semiconducting Polymeric Nanoagonists for Precision Sono-Immunotherapy of Head and Neck Squamous Cell Carcinoma.

Immunotherapy has offered new opportunities to treat head and neck squamous cell carcinoma (HNSCC); however, its clinical applications are hindered by modest therapeutic outcomes and the "always-on" pharmacological activity of immunomodulatory agents. Strategies for precise spatiotemporal activation of antitumor immunity can tackle these issues but remain challenging. Herein, a semiconducting polymeric nanoagonist (SPNM) with in situ sono-activatable immunotherapeutic effects for precision sono-immunotherapy of HNSCC is reported. SPNM is self-assembled from a sonodynamic semiconducting polymer core conjugated with a stimulator of interferon genes (STING) agonist (MSA-2) via a singlet oxygen cleavable linker. Under sono-irradiation, SPNM produces singlet oxygen not only to eradicate tumor cells to trigger immunogenic cell death but also to unleash caged STING agonists via the cleavage of diphenoxyethene bonds for in situ activation of the STING pathway in the tumor region. Such sono-driven STING activation mediated by SPNM promotes effector T cell infiltration and potentiates systemic antitumor immunity, eventually leading to tumor growth inhibition and long-term immunological memory. This study thus presents a promising strategy for the precise spatiotemporal activation of cancer immunotherapy.

Human milk expression in the first year postpartum among persons with low incomes.

BACKGROUND: Expressing milk (i.e., human milk) is common in the USA, but practices are unknown among families in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC). This study of a WIC population explores the practice of and reasons for expressing milk in the first year postpartum. METHODS: We analysed data from a longitudinal study to examine milk expression at 1, 3, 5, 7, 9, 11, and 13 months postpartum among breastfeeding persons enrolled in WIC with term singletons. We cross-sectionally analysed the weighted prevalence of milk expression at each survey month and report reasons for milk expression in the first 7 months. RESULTS: Among the study participants who reported feeding human milk at Month 1, 70.4% expressed milk in the first 13 months postpartum. The prevalence of milk expression was 56.8% at Month 1 and decreased to 13.9% at Month 13 among those feeding any human milk that month. Reasons for expressing milk changed over time; in the first month, increasing milk supply, relieving engorgement, and having an emergency supply of milk were common. In later months, having a supply of milk available so that someone else could feed their infant was common. CONCLUSIONS: Clinicians, health educators, WIC staff, and others working with WIC families can promote optimal expressed milk feeding and storage practices. Extra attention and support may be especially important in the first months postpartum when milk expression is common. Support for persons who are expressing milk can be tailored for reasons of milk expression.

The Promotional Effect of GW4869 on C. albicans Invasion and Cellular Damage in a Murine Model of Oral Candidiasis.

Candida albicans (C. albicans) is one of the most common fungi in the human body; it is an opportunistic pathogen and can cause candidiasis. Extracellular vesicles (EVs) derived from the host cells have a potentially protective effect against pathogens and can be developed as vaccine formulations. GW4869 can inhibit the production and release of EVs. Previous studies have indicated that GW4869 can alter the immune and inflammatory responses of the host. However, the effect of GW4869 on Candida infection and the anti-Candida response of the host has not been investigated. We evaluated the effect of GW4869 on C. albicans invasion, biofilm formation, and cellular damage in a murine model of oral candidiasis. In this study, C. albicans-infected mice were injected with or without GW4869. The results proven by macroscopic, microscopic, and ultramicroscopic methods showed that GW4869 treatment exacerbated the oral candidiasis of mice, promoted C. albicans invasion and biofilm formation, and aggravated oral mucosal inflammation and cellular ultrastructural damage. The results are beneficial in the further exploration of the immune mechanism of C. albicans infection.

Oral Bacteriome and Mycobiome across Stages of Oral Carcinogenesis.

Oral microbial dysbiosis contributes to the development of oral squamous cell carcinoma (OSCC). Numerous studies have focused on variations in the oral bacterial microbiota of patients with OSCC. However, similar studies on fungal microbiota, another integral component of the oral microbiota, are scarce. Moreover, there is an evidence gap regarding the role that microecosystems play in different niches of the oral cavity at different stages of oral carcinogenesis. Here, we catalogued the microbial communities in the human oral cavity by profiling saliva, gingival plaque, and mucosal samples at different stages of oral carcinogenesis. We analyzed the oral bacteriome and mycobiome along the health-premalignancy-carcinoma sequence. Some species, including Prevotella intermedia, Porphyromonas endodontalis, Acremonium exuviarum, and Aspergillus fumigatus, were enriched, whereas others, such as Streptococcus salivarius subsp. salivarius, Scapharca broughtonii, Mortierella echinula, and Morchella septimelata, were depleted in OSCC. These findings suggest that an array of signature species, including bacteria and fungi, are closely associated with oral carcinogenesis. OSCC-associated diversity differences, species distinction, and functional alterations were most remarkable in mucosal samples, not in gingival plaque or saliva samples, suggesting an urgent need to define oral carcinogenesis-associated microbial dysbiosis based on the spatial microbiome. IMPORTANCE Abundant oral microorganisms constitute a complex microecosystem within the oral environment of the host, which plays a critical role in the adjustment of various physiological and pathological states of the oral cavity. In this study, we demonstrated that variations in the "core microbiome" may be used to predict carcinogenesis. In addition, sample data collected from multiple oral sites along the health-premalignancy-carcinoma sequence increase our understanding of the microecosystems of different oral niches and their specific changes during oral carcinogenesis. This work provides insight into the roles of bacteria and fungi in OSCC and may contribute to the development of early diagnostic assays and novel treatments.

Breastfeeding and post-perinatal infant deaths in the United States, A national prospective cohort analysis.

Background: Reducing infant mortality is a major public health goal. The potential impact of breastfeeding on infant deaths is not well studied in the United States (US). Methods: We analyzed linked birth-death certificates for 3,230,500 US births that occurred in 2017, including 6,969 post-perinatal deaths from 7-364 days of age as the primary outcome, further specified as late-neonatal (7-27 days) or post-neonatal (28-364 days) deaths. The primary exposure was 'ever breastfed' obtained from birth certificates. Multiple logistic regression examined associations of ever breastfeeding with post-perinatal deaths and specific causes of deaths, controlling for maternal and infant factors. Findings: We observed an adjusted reduced odds ratio (AOR)= 0·74 with 95% confidence intervals (CI)=0·70-0·79 for the association of breastfeeding initiation with overall infant deaths (7-364 days), AOR=0·60 (0·54-0·67) for late-neonatal deaths, and AOR=0·81 (0·76-0·87) for post-neonatal deaths. In race/ethnicity-stratified analysis, significant associations of breastfeeding initiation with reduced odds of overall infant deaths were observed for Hispanics [AOR=0·64 (0·55-0·74)], non-Hispanic Whites [AOR=0·75 (0·69-0·81)], non-Hispanic Blacks [AOR=0·83 (0·75-0·91)], and non-Hispanic Asians [AOR=0·51 (0·36-0·72)]. Across racial/ethnic groups, effect sizes for late-neonatal deaths were consistently larger than those for post-neonatal deaths. Significant effects of breastfeeding initiation were observed for deaths due to infection [AOR=0·81(0·69-0·94)], Sudden Unexpected Infant Death [AOR=0·85 (0·78-0·92)], and necrotizing enterocolitis [AOR=0·67 (0·49-0·90)]. Interpretation: Breastfeeding initiation is significantly associated with reduced odds of post-perinatal infant deaths in multiple racial and ethnic groups within the US population. These findings support efforts to improve breastfeeding in infant mortality reduction initiatives.

[Development of a Wireless Wearable Body Temperature Measurement System Based on NTC].

Body temperature is an important physiological parameter of the human body and is used in medicine to reflect the physiological state and health status of the human body. At present, the commonly used clinical thermometers on the market are mainly divided into contact and non-contact types. Most of them are used for rapid body temperature measurement, and it is not easy to monitor body temperature changes in real time. This article introduces a new wearable wireless body temperature monitoring system based on NTC, which senses through NTC. The temperature changes are amplified and filtered, zeroed, and calibrated, and then the temperature data is uploaded to the mobile phone APP via Bluetooth in real time to achieve real-time accurate measurement of body temperature.

Antimicrobial Effect of Extracellular Vesicles Derived From Human Oral Mucosal Epithelial Cells on Candida albicans.

Candida albicans (C. albicans) is a commensal microorganism that colonizes the mucosal surfaces of healthy individuals. Changes in the host or environment can lead to overgrowth of C. albicans and infection of the host. Extracellular vesicles (EVs) are released by almost all cell types and play an increasingly recognized role in fighting microbial infection. The aim of the present study was to assess whether EVs derived from human oral mucosal epithelial (Leuk-1) cells can suppress the growth and invasion of C. albicans. The in vitro efficacy of Leuk-1-EVs against C. albicans was assessed by optical microscopy, laser scanning confocal microscopy, scanning electron microscopy, and transmission electron microscopy. The germ tube formation rate, the percentage of hyphae and the microcolony optical density were also used to analyze the growth of C. albicans in a coculture model with Leuk-1 cells and EVs or after inhibition of the secretion of EVs. A mouse model of oral candidiasis was established and submucosal injection of Leuk-1-EVs in the tongue was performed. Macroscopic observation, H&E staining, PAS staining, and scanning electron microscopy were used to assess antifungal effects of Leuk-1-EVs in vivo. The in vitro results showed that the growth of C. albicans was inhibited and that the morphology and ultrastructure were changed following Leuk-1-EVs treatment. The in vivo results exhibited that white lesions of the tongue, C. albicans infection, and oral mucosal inflammation of the infected mice were significantly alleviated after Leuk-1-EVs treatment. We thus reveal an antifungal capability of EVs derived from oral epithelial cells against C. albicans that is mediated by direct damage effects and potential synergy between EVs and human oral mucosal epithelial cells. This finding offers an intriguing, previously overlooked method of antifungal defense against C. albicans.