A tumor-promotional molecular axis CircMAPKBP1/miR-17-3p/TGFß2 activates autophagy pathway to drive tongue squamous cell carcinoma cisplatin chemoresistance.

Platinum-based chemotherapy is the first-line treatment for tongue squamous cell carcinoma (TSCC), but most patients rapidly develop resistance. Circular RNAs (circRNAs) are a class of critical regulators in the pathogenesis of several tumors, but their role in cisplatin resistance in TSCC has not been fully elucidated. Here we found that circMAPKBP1 was enriched in cisplatin resistant TSCC cells and was closely associated with enhanced autophagic activity. Functionally, silencing circMAPKBP1 significantly restored the chemosensitivity of cisplatin-resistant TSCC cells both in vitro and in vivo by suppressing autophagy. Mechanistically, circMAPKBP1 enhanced cisplatin sensitivity through the miR-17-3p/TGFß2 axis by activating autophagy pathway. Data from clinical studies revealed that high expression of circMAPKBP1 and TGFß2 was closely linked to a poor outcome in TSCC patients. We thus concluded that circMAPKBP1 is a tumor promoting factor and confers cisplatin sensitivity by activating the miR-17-3p/TGFß2 axis-mediated autophagy. We propose that circMAPKBP1 may be a potential therapeutic target for TSCC.

Physical and chemical characterization of chitin and chitosan extracted under different treatments from black soldier fly.

The shell of Hermetia illucens L. contains considerable amounts of chitin, which has various biological activities. So far, few studies have focused on chitin of Hermetia illucens L. as a source of chitosan and oligosaccharides. There is great potential for utilizing Hermetia illucens L. chitin to produce chitosan films in biomaterials. We studied different extraction conditions for chitin and extracted it from black soldier fly (BSF) (Hermetia illucens L.). Three processing steps were adopted: (1) demineralization, (2) deproteinization, and (3) decolorization. The chemical components (moisture, ash, protein, fat, residual protein, and residual mineral contents) and physicochemical characteristics of the chitin and chitosan extracted under these three conditions were determined. In addition, Fourier transform infrared spectroscopy and X-ray diffraction were used to analyze the extracted chitin and commercial samples, and the results showed that demineralization-deproteinization-decolorization treatments could achieve the highest chitin yield (7.18 ±â€¯0.11 %), chitosan yield (64.22 ±â€¯0.79 %), and the best purity (residual protein 0.56 ±â€¯0.01 % and residual ash 0.58 ±â€¯0.04 %), making it the best treatment method. Using this method, the residues produced from farmed BSF can be recycled and used as a new source of chitin.

The impact of test anxiety on oral microbiota among medical students-A pilot study.

Test anxiety (TA) is a common emotion among students during examinations. Test-induced stress can remarkably impact students' emotions and limit their performance. Mental stress is a crucial factor that could significantly alter gut microbial composition, but rare reports focus on the correlation between TA and oral microbial composition. This study aims to investigate the impact of TA on students' oral microbiota composition. This study targeted medical students who usually face heavier workloads than average undergraduates. 28 females and 19 males aged 18-30 were enrolled in this study. Questionnaires and saliva samples were collected from the participants before, during, and after the end-term examination. The level of anxiety was classified as normal, mild, moderate, and severe based on the questionnaire scores. In addition, 16S amplicon sequencing was used to analyse the composition of oral microbes. More than half of the students faced different levels of TA before and after the examination. Over three-quarters of students showed anxiety during the examination, and a quarter suffered severe TA. The 16S sequencing data showed that TA significantly altered the oral microbial composition between students with and without TA in all three survey periods. Moreover, during the examination, the genera Rothia and Streptococcus, the oral-beneficial bacteria, markedly decreased in students with TA. On the other hand, the potential pathogenic genera, such as Prevotella, Fusobacterium, and Haemophilus, significantly increased in the students with TA. And the TA effect on oral microbes displayed a gender difference among students. A high ratio of TA existed in the students during their examination period, and TA could significantly alter the oral microbial composition, decrease beneficial microbes, and promote potential pathogenic oral microbes.

The m6A Reader IGF2BP2 Promotes Oral Squamous Cell Carcinoma Progression by Maintaining UCA1 Stability.

INTRODUCTION: N6-methyladenosine (m6A) modifications of RNAs are associated with many cancer types. Nevertheless, the function of the m6A reader IGF2BP2 in oral squamous cell carcinoma (OSCC) has yet to be ascertained. AIMS: The objective of this investigation was to elucidate the role of IGF2BP2 in OSCC and delineate the associated mechanisms. METHOD: Elevated expression of IGF2BP2 was observed in OSCC, and this overexpression significantly correlated with adverse prognostic outcomes in patients with OSCC. In vitro analyses demonstrated that silencing of IGF2BP2 attenuated the proliferation, migration, and invasion capabilities of oral cancer cells while concurrently promoting apoptosis. RESULTS: In vivo experiments demonstrated that IGF2BP2 promoted OSCC growth. RNA-seq and m6A-seq were utilized to elucidate the downstream targets of IGF2BP2. Through bioinformatic analysis, we identified the long noncoding RNA (lncRNA) UCA1 as a target. IGF2BP2 was found to maintain the stability of UCA1 in an m6A-dependent manner by binding to m6A-modified UCA1 and plays an oncogenic role in OSCC through UCA1. CONCLUSION: In conclusion, we identified IGF2BP2 as a prognostic biomarker of OSCC, and the IGF2BP2-UCA1 axis was found to promote OSCC progression and may perform as a novel therapeutic target.

Blueberry extract for the treatment of ischaemic stroke through regulating the gut microbiota and kynurenine metabolism.

Although the gut microbiota and kynurenine (KYN) metabolism have significant protective effects against ischaemic stroke (IS), the exact mechanism has yet to be fully elucidated. Combined serum metabolomics and 16S rRNA gene sequencing were used to reveal the differences between the gut microbiota and metabolites in rats treated with or without blueberry extract. Faecal microbiota transplantation (FMT) was employed to validate the protective role of the gut microbiota in IS. Furthermore, the interaction between Prevotella and IS was also confirmed in patients. Rats with IS experienced neurological impairments accompanied by an impaired intestinal barrier and disturbed intestinal flora, which further contributed to heightened inflammatory responses. Furthermore, Prevotella played a critical role in IS pathophysiology, and a positive correlation between Prevotella and KYN was detected. The role of KYN metabolism in IS was further demonstrated by the finding that IDO was significantly upregulated and that the use of the IDO inhibitor, attenuated KYN metabolic pathway activity and ameliorated neurological damage in rats with IS. Prevotella intervention also significantly improved stroke symptoms and decreasing KYN levels in rats with IS. FMT showed that the beneficial effects of blueberry extract on IS involve gut bacteria, especially Prevotella, which were confirmed by microbiological analyses conducted on IS patients. Moreover, blueberry extract led to significant changes in kynurenic acid levels and tryptophan and IDO levels through interactions with Prevotella. Our study demonstrates for the first time that blueberry extract could modulate "intestinal microecology-KYN metabolism" to improve IS.

The association between SII and aging: evidence from NHANES 1999-2018.

Background: The study aimed to examine the association between the systemic immune-inflammation index (SII), a contemporary metric of systemic inflammatory response, and biological aging, which are closely interconnected processes. Methods: This cross-sectional study utilized 10 cycles of data from the NHANES database spanning from 1990 to 2018. The study examined the relationship between the SII index, calculated as P * N/L, where P represents preoperative peripheral platelet count, N represents neutrophil count, and L represents lymphocyte count, and biological aging. Biological aging was assessed through various methods, such as phenotypic age, phenotypic age acceleration (PhenoAgeAccel), biological age, and biological age acceleration (BioAgeAccel). Correlations were analyzed using weighted linear regression and subgroup analysis. Results: Among the 7,491 participants analyzed, the average age was 45.26 ± 0.34 years, with 52.16% being female. The average phenotypic and biological ages were 40.06 ± 0.36 and 45.89 ± 0.32 years, respectively. Following adjustment for potential confounders, elevated SII scores were linked to increased phenotypic age, biological age, Phenotypic age acceleration, and Biological age acceleration. Positive correlations were observed between health behavior and health factor scores and biological aging, with stronger associations seen for health factors. In health factor-specific analyses, the ß coefficient was notably higher for high BMI. The robust positive associations between SII scores and both phenotypic age and biological age in the stratified analyses were consistently observed across all strata. Conclusion: The evidence from the NHANES data indicate that SII may serve as a valuable marker for assessing different facets of aging and health outcomes, such as mortality and the aging process. Additional research is warranted to comprehensively elucidate the implications of SII in the aging process and its utility as a clinical instrument for evaluating and addressing age-related ailments.

Desulfovibrio vulgaris caused gut inflammation and aggravated DSS-induced colitis in C57BL/6 mice model.

BACKGROUND: Sulfate-reducing bacteria (SRB) is a potential pathogen usually detected in patients with gastrointestinal diseases. Hydrogen sulfide (H2S), a metabolic byproduct of SRB, was considered the main causative agent that disrupted the morphology and function of gut epithelial cells. Associated study also showed that flagellin from Desulfovibrio vulgaris (DVF), the representative bacterium of the Desulfovibrio genus, could exacerbate colitis due to the interaction of DVF and LRRC19, leading to the secretion of pro-inflammatory cytokines. However, we still have limited understanding about the change of gut microbiota (GM) composition caused by overgrowth of SRB and its exacerbating effects on colitis. RESULTS: In this study, we transplanted D. vulgaris into the mice treated with or without DSS, and set a one-week recovery period to investigate the impact of D. vulgaris on the mice model. The outcomes showed that transplanted D. vulgaris into the normal mice could cause the gut inflammation, disrupt gut barrier and reduce the level of short-chain fatty acids (SCFAs). Moreover, D. vulgaris also significantly augmented DSS-induced colitis by exacerbating the damage of gut barrier and the secretion of inflammatory cytokines, for instance, IL-1ß, iNOS, and TNF-α. Furthermore, results also showed that D. vulgaris could markedly change GM composition, especially decrease the relative abundance of SCFAs-producing bacteria. Additionally, D. vulgaris significantly stimulated the growth of Akkermansia muciniphila probably via its metabolic byproduct, H2S, in vivo. CONCLUSIONS: Collectively, this study indicated that transplantation of D. vulgaris could cause gut inflammation and aggravate the colitis induced by DSS.

Causal association of circulating immune cells and lymphoma: A Mendelian randomization study.

Background: Malignant lymphoma (ML) is a group of malignant tumors originating from the lymphatic hematopoietic system. Previous studies have found a correlation between circulating immune cells and ML. Nonetheless, the precise influence of circulating immune cells on ML remains uncertain. Methods: Based on publicly available genetic data, we explored causal associations between 731 immune cell signatures and ML risk. A total of four types of immune signatures, median fluorescence intensities, relative cell, absolute cell, and morphological parameters were included. Primary analysis was performed using inverse variance weighting (IVW) to assess the causal relationship between circulating immune cells and the risk of ML. Sensitivity analysis was conducted using Cochran's Q test, the Mendelian randomization Egger regression intercept test, and leave-one-out analysis. Results: ML had a statistically significant effect on immunophenotypes. Twenty-three immunophenotypes were identified to be significantly associated with Hodgkin lymphoma risk through the IVW approach, and the odds ratio values of CD64 on CD14- CD16+ monocyte [2.31, 95% confidence interval (CI) = 1.41-3.79, P1 = 0.001], IgD+ CD24+ B-cell %lymphocyte (2.06, 95% CI = 1.13-3.79, P1 = 0.018), B-cell %lymphocyte (1.94, 95% CI = 1.08-3.50, P1 = 0.027), CD24+ CD27+ B-cell %lymphocyte (1.68, 95% CI = 1.03-2.74, P1 = 0.039), and CD14+ CD16- monocyte %monocyte (1.60, 95% CI = 1.15-2.24, P1 = 0.006) ranked in the top five. Eleven immunophenotypes were identified to be significantly associated with non-Hodgkin lymphoma risk, CD86 on granulocyte (2.35, 95% CI = 1.18-4.69, P1 = 0.015), CD28-CD8+ T-cell absolute count (1.76, 95% CI = 1.03-2.99, P1 = 0.036), CCR2 on myeloid dendritic cell (CD24+ CD27+ B cell, 95% CI = 1.02-1.66, P1 = 0.034), CD3 on effector memory CD8+ T cell (1.29, 95% CI = 1.02-1.64, P1 = 0.012), and natural killer T %lymphocyte (1.28, 95% CI = 1.01-1.62, P1 = 0.046) were ranked in the top five. Conclusion: This study presents compelling evidence indicating the correlation between circulating immune cells and lymphoma, thus providing guidance for future clinical research.

Global, regional and national burdens of Nasopharynx cancer in the adolescents and young adults from 1990 to 2019 and its predictions.

PURPOSE: To use data from the Global Burden of Disease (GBD) Study 2019 to report the global, regional and national rates and trends of deaths incidence, prevalence, disability-adjusted life years (DALYs) for Nasopharynx cancer (NPC) in adolescents and young adults (AYAs). METHODS: Data from the GBD 2019 were used to analyze deaths incidence, prevalence and DALYs due to NPC at global, regional, and national levels. Joinpoint regression analysis was used to calculate the average annual percentage changes (AAPC). The association between incidence, prevalence and DALYs and socioeconomic development was analyzed using the GBD Socio-demographic Index (SDI). Finally, projections were made until 2030 and calculated in Nordpred. RESULTS: The incidence, prevalence, death and DALYs rates (95%UI) due to NPC 0.96 (0.85-1.09, 6.31 (5.54-7.20),0.20 (0.19-0.22), and 12.23(11.27-13.29) in 2019, respectively. From 1990 to 2019, the incidence and prevalence rates increased by 1.79 (95% CI 1.03 to 2.55) and 2.97(95% CI 2.13 to 3.82) respectively while the deaths and DALYs rates declined by 1.64(95%CI 1.78 to 1.49) and 1.6(95%CI 1.75 to 1.4) respectively. Deaths and DALYs rates in South Asia, East Asia, North Africa and Middle East decreased with SDI. Incidence and prevalence rates in East Asia increased with SDI. At the national level, the incidence and prevalence rates are high in China, Taiwan(China), Singapore, Malaysia, Brunel Darussalam, Algeria, Tunisia, Libya and Malta. Meanwhile, the deaths and DALYs rates are still high in Malaysia, Brunel Darussalam, Greenland and Taiwan(Province of China). The deaths and DALYs rates are low in Honduras, Finland and Norway. From the 2020 to 2030, ASIR、ASPR and ASDR in most regions are predicted to stable, but DALYs tends to decline. CONCLUSION: NPC in AYAs is a significant global public problem. The incidence, prevalence, and DALYs rates vary widely by region and country. Therefore different regions and countries should be targeted to improve the disease burden of NPC.

Neoadjuvant chemoimmunotherapy in resectable locally advanced oral squamous cell carcinoma: a single-center retrospective cohort study.

BACKGROUND: Surgery and postoperative adjuvant therapy is the standard treatment for locally advanced resectable oral squamous cell carcinoma (OSCC), while neoadjuvant chemoimmunotherapy (NACI) is believed to lead better outcomes. This study aims to investigate the effectiveness of NACI regimens in treating locally advanced resectable OSCC. MATERIALS AND METHODS: Patients diagnosed with locally advanced resectable OSCC who received NACI and non-NACI were reviewed between December 2020 and June 2022 in our single center. The pathologic response was evaluated to the efficacy of NACI treatment. Adverse events apparently related to NACI treatment were graded by Common Terminology Criteria for Adverse Events, version 5.0. Disease-free survival (DFS) and overall survival (OS) rate were assessed. RESULTS: Our analysis involved 104 patients who received NACI. Notably, the pathological complete response (PCR) rate was 47.1%, and the major pathological response (MPR) rate was 65.4%. The top three grade 1-2 treatment-related adverse events (TRAEs) were alopecia (104; 100%), anemia (81; 77.9%) and pruritus (62; 59.6%). Importantly, patients achieving MPR exhibited higher programmed cell death-ligand 1 (PD-L1) combined positive score (CPS). The diagnostic value of CPS as a biomarker for NACI efficacy was enhanced when combined total cholesterol level. The 3-year estimated DFS rates were 89.0% in the NACI cohort compared to 60.8% in the non-NACI cohort, while the 3-year estimated OS rates were 91.3% versus 64.0%, respectively. CONCLUSIONS: The NACI treatment showed safe and encouragingly efficacious for locally advanced resectable OSCC patients. The high response rates and favorable prognosis suggest this approach as a potential treatment option. Prospective randomized controlled trials are needed to further validate these findings.

Association between added sugars and frailty in U.S. adults: a cross-sectional study from the National Health and Nutrition Examination Survey 2007-2018.

Objective: There are various detrimental effects of excessive added sugar consumption on health, but the association of added sugars with frailty remains elusive. We aimed to examine the association between added sugar intake and frailty among American adults in the present cross-sectional study. Methods: This cross-sectional study is based on the National Health and Nutrition Examination Survey (NHANES) database. Data from NHANES spanning from 2007 to 2018 on frailty, added sugars, and covariates were collected. Added sugars were categorized into quartiles according to the recommended percentages by institutions. Weighted multivariable logistic regression was used to analyze the relationship between frailty and added sugars. Subgroup analysis was conducted based on sex, age, body mass index (BMI), smoking, alcohol consumption, hypertension, and diabetes status. Results: This study included 16,381 participants, with 13,352 (81.51%) in the non-frailty group and 3,029 (18.49%) in the frailty group. We found that added sugars were positively associated with frailty, and subgroup analysis showed that participants who were male, over the age of 60, had a low BMI, had previously smoked and consumed alcohol, had no hypertension, or had diabetes mellitus (DM) were more likely to be frail. Added sugar intake was positively associated with frailty. Subgroup analysis showed that the association was strongest in males, those aged >60, those with a low BMI, former smokers, former alcohol consumers, and people with no hypertension or DM. When added sugars are classified by energy percentage, populations with more than 25% of their energy coming from added sugars have similar results, with a higher prevalence of frailty. Conclusion: Added sugars are positively associated with a higher risk of frailty, and the association is stable among different populations.

The clinical application of V-Y advanced flap pedicled with freestyle perforator flap for repairing small range defects in the anterior knee region.

Introduction: This study aims to investigate the clinical efficacy of V-Y advanced flap pedicled with freestyle perforator flap for repairing small range defects in the anterior knee region. Methods: 8 patients with skin and soft tissue defect/necrosis in the anterior knee area admitted to the Changshu No.1 People's Hospital from January 2021 to January 2022 were selected, with a defect range of 4 cm × 3 cm-9 cm × 6 cm, designed a V-Y advanced flap pedicled with freestyle perforator flap to repair the wound in the anterior knee area. Adjust the size and position of the flap according to the number and position of perforating branches found during the surgery, with a cutting area of 6 cm × 5 cm-14 cm × 10 cm and the supply area was directly pulled and sutured. Results: 4 patients were repaired by flaps pedicled with 2 perforating branches, 2 patients were repaired by flaps pedicled with 1 perforating branch and 2 patients were repaired by flaps pedicled with 3 perforating branches. 4 patients were repaired by flaps pedicled with 2 perforating branches, 2 patients were repaired by flaps pedicled with 1 perforating branch and 2 patients were repaired by flaps pedicled with 3 perforating branches. All flaps survived and following up for 6-15 months, the blood supply, appearance, and color of the flap were satisfactory, and the functions of knee joint flexion and extension were well preserved. Discussion: The V-Y advancement flap pedicled with freestyle perforator flap has the advantages of reliable blood supply, simple surgical operation, texture and thickness similar to the skin of the anterior knee area, and direct suture of the donor area. It is a perforator flap with good repair effect for small scale defects in the anterior knee area.

Causal analysis of body composition measurements in osteoarthritis knee: a two-sample mendelian randomization study.

BACKGROUND: To analyse the causal associations of different physical measures with osteoarthritis knee (KOA). METHODS: Exposure factors (weight, body mass index (BMI), body fat percentage, waist circumference, hip circumference, waist-hip ratio (WHR), and basal metabolic rate (BMR)), and outcome factor KOA were analyzed by inverse-variance weighted (IVW) method, along with heterogeneity test, sensitivity and pleiotropy analyses. Meta-analysis was used to combine the effect values of IVW methods in different data sources. RESULTS: Weight, BMI, body fat percentage, waist circumference, hip circumference and BMR analyses showed causal association with increased KOA risk, while WHR analysis indicated a reduction of the incidence of KOA. P-value for all the results was less than 0.05 and F-value large than 20. All results were negative for heterogeneity tests and sensitivity analyses, and there was pleiotropy in weight and BMR. Meta-analysis results showed that the results of Odds Ratios (95% Confidence Intervals) for Weight (1.43(1.35-1.51)), BMI (1.40(1.10-1.78)), body fat percentage (1.56(1.44-1.68)), waist circumference (1.40(1.10-1.78)), hip circumference (1.37(1.30-1.44)), WHR (0.86(0.71-1.04)) and BMR (1.36(1.27-1.46) were consistent with the ones by Mendelian randomization analyses. CONCLUSIONS: Body fat percentage may be a better indicator of KOA than BMI. In addition, weight and BMR may have a causal effect in KOA, but WHR does not have a causal relationship. BMI, body fat percentage, waist circumference, and hip circumference has a causal effect on KOA.

The burden of low back pain in adolescents and young adults.

BACKGROUND: Low back pain is highly prevalent and the main cause of years lived with disability, but data on the burden and trends of low back pain (LBP) in adolescents and young adults (AYAs) are sparse. OBJECTIVE: To assess trends in the burden of LBP among AYAs aged 15-39 years at the global, regional and national levels from 1990 to 2019. METHODS: Data from the Global Burden of Disease (GBD) 2019 were used to analyze incidence, prevalence and Disability-adjusted life year (DALY) due to LBP at global, regional, and national levels. Joinpoint regression analysis calculated the average annual percentage changes (AAPC). Then analyse the association between incidence, prevalence and DALYs and socioeconomic development using the GBD Socio-demographic Index (SDI). Finally, projections were made until 2030 and calculated in Nordpred. RESULTS: The incidence, prevalence and DALYs rates (95%UI) were 2252.78 (1809.47-2784.79), 5473.43 (4488.62-6528.15) and 627.66 (419.71-866.97) in 2019, respectively. From 1990 to 2019, the incidence, prevalence, and DALYs rates AAPC (95%CI) were -0.49 (-0.56 to -0.42), -0.58 (-0.65 to -0.51) and -0.57 (-0.64 to -0.5), respectively. Incidence, prevalence, and DALYs rates in South Asia, East Asia, High-income North America, Western Europe, and Australasia decreased with SDI. Incidence, prevalence, and DALYs rates in Central Asia, Central Europe, and Eastern Europe decreased and then increased with SDI. At the national level, the incidence, prevalence, and DALYs rates are high in the United States and low in India and China. From the 2020 to 2030, most regions is predicted to decline. CONCLUSION: LBP in AYAs is a major global public problem with a high burden. There are large differences in incidence, prevalence and DALYs across SDIs, regions and countries. there is still a need to focus on LBP in AYAs and tailor interventions to reduce the future burden of this condition.

The association between lipid biomarkers and osteoarthritis based on the National Health and Nutrition Examination Survey and Mendelian randomization study.

To explore the association between lipid markers and osteoarthritis (OA). First, the National Health and Nutrition Examination Survey (NHANES) database was used to screen participants with lipid markers, OA and relevant covariates, and logistic regression was used to analyze the association between lipid markers and OA; Then, under the theoretical framework of Mendelian randomization (MR), two-sample MR was performed using GWAS data of lipid markers and OA to explore the causal association between the two, which was analyzed by inverse variance weighting (IVW) method. Heterogeneity test, sensitivity analysis and pleiotropy analysis were also performed. The NHANES database screened a total of 3706 participants, of whom 836 had OA and 2870 did not have OA. When lipid markers were used as continuous variables, multivariate logistic results showed an association between HDL, LDL and OA (HDL, OR (95%):1.01 (1.00, 1.01); LDL, OR (95%):1.00 (0.99, 1.00)). When lipid markers were used as categorical variables, multivariate logistic results showed the fourth quartile result of 0.713 (0.513, 0.992) for LDL relative to the first quartile. In MR study, the results of the IVW method for TG, TL, HDL and LDL showed OR (95% CI) of 1.06 (0.97-1.16), 0.95 (0.85-1.06), 0.94 (0.86-1.02) and 0.89 (0.80-0.998) with P-values of 0.21, 0.37. 013, 0.046. The heterogeneity tests and multiplicity analyses showed P-values greater than 0.05, and sensitivity analyses showed no abnormal single nucleotide polymorphisms. Through NHANES database and MR analyses, LDL was found to be a protective factor for OA, while HDL still needs further study. Our results provide new biomarkers for preventive and therapeutic strategies for OA.

Relationship between rumen bacterial community and milk fat in dairy cows.

Introduction: Milk fat is the most variable nutrient in milk, and recent studies have shown that rumen bacteria are closely related to milk fat. However, there is limited research on the relationship between rumen bacteria and milk fatty. Fatty acids (FAs) are an important component of milk fat and are associated with various potential benefits and risks to human health. Methods: In this experiment, forty-five healthy Holstein dairy cows with alike physiological and productive conditions were selected from medium-sized dairy farms and raised under the same feeding and management conditions. The experimental period was two weeks. During the experiment, raw milk and rumen fluid were collected, and milk components were determined. In this study, 8 high milk fat percentage (HF) dairy cows and 8 low milk fat percentage (LF) dairy cows were selected for analysis. Results: Results showed that the milk fat percentage in HF group was significantly greater than that of the dairy cows in the LF group. 16S rRNA gene sequencing showed that the rumen bacterial abundance of HF dairy cows was significantly higher than that in LF dairy cows; at the genus level, the bacterial abundances of Prevotellaceae_UCG-001, Candidatus_Saccharimonas, Prevotellaceae_UCG-003, Ruminococcus_1, Lachnospiraceae_XPB1014_group, Lachnospiraceae_AC2044_group, probable_genus_10 and U29-B03 in HF group were significantly higher than those in the LF group. Spearman rank correlation analysis indicated that milk fat percentage was positively related to Prevotellaceae_UCG-001, Candidatus_Saccharimonas, Prevotellaceae_UCG-003, Ruminococcus_1, Lachnospiraceae_XPB1014_group, Lachnospiraceae_AC2044_group, probable_genus_10 and U29-B03. Furthermore, Prevotellaceae_UCG-001 was positively related to C14:0 iso, C15:0 iso, C18:0, Ruminococcus_1 with C18:1 t9, Lachnospiraceae_AC2044_group with C18:1 t9 and C18:1 t11, U29-B03 with C15:0 iso. Discussion: To sum up, rumen bacteria in dairy cows are related to the variation of milk fat, and some rumen bacteria have potential effects on the deposition of certain fatty acids in raw milk.

The relationship between prebiotic intake and allergic rhinitis.

Objectives: Exploring the relationship between intake of probiotics and the prevalence of allergic rhinitis. Methods: Based on data from the National Health and Nutrition Examination Survey, dietary supplement labels were examined to identify products containing probiotics and prebiotics. Statistical methods were used to analyze the factors influencing the prevalence of allergic rhinitis, and further stratified analysis was conducted to control for confounding factors. Results: The proportion of individuals not consuming probiotics was significantly higher in the allergic rhinitis (AR) group than in those consuming them, suggesting a correlation between probiotics and AR. In the male subgroup with probiotic intake, the adjusted odds ratio (95% confidence interval) was 0.28 (0.10-0.75), p = .02, indicating that probiotic intake was a protective factor for AR in the male population. In the probiotic-intake group, the odds ratio for age < 65 was 0.26 (0.07-0.94), p = .04, and for age ≥ 80 was less than 1 with p < .0001, suggesting that probiotic intake was a protective factor for AR in age < 65 and age ≥ 80 populations, both with statistical significance. Conclusion: Intake of probiotics is associated with a reduced prevalence of allergic rhinitis, particularly in the male population and individuals aged <65 years and ≥ 80 years. Level of Evidence: Level 4.

Intratumoral CD103+ CD8+ T cells predict response to neoadjuvant chemoimmunotherapy in advanced head and neck squamous cell carcinoma.

BACKGROUND: Immune cell heterogenicity is known to determine the therapeutic response to cancer progression. Neoadjuvant chemoimmunotherapy (NACI) has shown clinical benefits in some patients with advanced head and neck squamous cell carcinoma (HNSCC), but the underlying mechanism behind this clinical response is unknown. The efficacy of NACI needs to be potentiated by identifying accurate biomarkers to predict clinical responses. Here, we attempted to identify molecules predicting NACI response in advanced HNSCC. METHODS: We performed combined single-cell RNA sequencing (scRNA-seq) and multiplex immunofluorescence (mIHC) staining with tumor samples derived from NACI-treated HNSCC patients to identify a new tumor-infiltrating cell (TIL) subtype, CD103+ CD8+ TILs, associated with clinical response, while both in vitro and in vivo assays were carried out to determine its antitumor efficiency. The regulatory mechanism of the CD103+ CD8+ TILs population was examined by performing cell-cell interaction analysis of the scRNA-seq data and spatial analysis of the mIHC images. RESULTS: We established intratumoral CD103+ CD8+ TILs density as a determinant of NACI efficacy in cancers. Our scRNA-seq results indicated that the population of CD103+ CD8+ TILs was dramatically increased in the responders of NACI-treated HNSCC patients, while mIHC analysis confirmed the correlation between intratumoral CD103+ CD8+ TILs density and NACI efficacy in HNSCC patients. Further receiver operating characteristic curve analysis defined this TIL subset as a potent marker to predict patient response to NACI. Functional assays showed that CD103+ CD8+ TILs were tumor-reactive T cells, while programmed cell death protein-1 (PD-1) blockade enhanced CD103+ CD8+ TILs cytotoxicity against tumor growth in vivo. Mechanistically, targeting the triggering receptor expressed on myeloid cells 2-positive (TREM2+ ) macrophages might enhance the population of CD103+ CD8+ TILs and facilitate antitumor immunity during NACI treatment. CONCLUSIONS: Our study highlights the impact of intratumoral CD103+ CD8+ TILs density on NACI efficacy in different cancers, while the efforts to elevate its population warrant further clinical investigation.

The association between frailty and osteoarthritis based on the NHANES and Mendelian randomization study.

Introduction: The aim of the study was to examine the association between frailty and osteoarthritis. Methods: We conducted a cross-sectional study in the National Health and Nutrition Examination Survey, while logistic regression was used to explore the association of the two. Mendelian randomization (MR) study was used to explore the causal relationship between the two. Results: In the cross-sectional study, logistic regression analysis showed that odds ratio (OR) (95% CI) value was 1.07 (1.05, 1.08). In the MR study, the inverse-variance weighting (IVW) results showed OR (95% CI) value of 1.69 (1.01-2.83). Conclusions: There is both a correlation and a causal relationship between frailty and osteoarthritis, and frailty may be a potentially better response than age to osteoarthritis.

Gut microbiome causal impacts on the prognosis of breast cancer: a Mendelian randomization study.

BACKGROUND: Growing evidence has shown that gut microbiome composition is associated with breast cancer (BC), but the causality remains unknown. We aimed to investigate the link between BC prognosis and the gut microbiome at various oestrogen receptor (ER) statuses. METHODS: We performed a genome-wide association study (GWAS) to analyse the gut microbiome of BC patients, the dataset for which was collected by the Breast Cancer Association Consortium (BCAC). The analysis was executed mainly via inverse variance weighting (IVW); the Mendelian randomization (MR) results were verified by heterogeneity tests, sensitivity analysis, and pleiotropy analysis. RESULTS: Our findings identified nine causal relationships between the gut microbiome and total BC cases, with ten and nine causal relationships between the gut microbiome and ER-negative (ER-) and ER-positive (ER+) BC, respectively. The family Ruminococcaceae and genus Parabacteroides were most apparent among the three categories. Moreover, the genus Desulfovibrio was expressed in ER- BC and total BC, whereas the genera Sellimonas, Adlercreutzia and Rikenellaceae appeared in the relationship between ER + BC and total BC. CONCLUSION: Our MR inquiry confirmed that the gut microbiota is causally related to BC. This further explains the link between specific bacteria for prognosis of BC at different ER statuses. Considering that potential weak instrument bias impacts the findings and that the results are limited to European females due to data constraints, further validation is crucial.