Association of oral microbiome with oral human papillomavirus infection: a population study of the National Health and Nutrition Examination Survey, 2009-2012.

BACKGROUND: Oral human papillomavirus(HPV) infection and the oral microbiome are associated with oropharyngeal cancer. However, population-based data on the association of oral microbiome with oral HPV infection are limited. METHOD: We performed a cross-sectional analysis of 5,496 participants aged 20-59 in National Health and Nutrition Examination Surveys(NHANES):2009-2012. The association between either oral microbiome alpha diversity or beta diversity and oral HPV infection was assessed using multivariable logistic regression or principal coordinate analyses(PCoA) and multivariate analysis of variance(PERMANOVA). RESULTS: For alpha diversity, we found a lower number of observed Amplicon sequence variants(ASVs) (adjusted odds ratio[aOR] = 0.996; 95%CI = 0.992-0.999) and reduced Faith's Phylogenetic Diversity(aOR = 0.95; 95%CI = 0.90-0.99) associated with high-risk oral HPV infection in the overall population. This trend was observed in males for both high-risk and any oral HPV infection. Beta diversity showed differentiation of oral microbiome community by high-risk oral HPV infection as measured by Bray-Curtis dissimilarity (R2 = 0.054%; P = .029) and unweighted UniFrac distance (R2 = 0.046%; P = .045) among the overall population, and associations were driven by males. CONCLUSIONS: Both oral microbiome alpha diversity(within-sample richness and phylogenetic diversity) and beta diversity(heterogeneous dispersion of oral microbiome community) are associated with HPV infection. Longitudinal studies are needed to characterize the role of the microbiome in the natural history of oral HPV infection.

Cobalt-vanadium sulfide yolk-shell nanocages from surface etching and ion-exchange of ZIF-67 for ultra-high rate-capability sodium ion battery.

Development of high-performance metal sulfides anode materials is a great challenge for sodium-ion batteries (SIBs). In this work, a cobalt-based imidazolate framework (ZIF-67) were firstly synthesized and applied as precursor. After the successive surface etching, ion exchange and sulfidation processes, the final cobalt-vanadium sulfide yolk-shell nanocages were obtained (CoS2/VS4@NC) with VS4 shell and CoS2 yolk encapsulated into nitrogen doped carbon frameworks. This yolk-shell nanocage structure effectively increases the specific surface area and provides enough space for inhibiting the volume change during charge/discharge processes. Besides, the nitrogen doped carbon skeleton greatly improves the ionic conductivity and facilitates ion transport. When used as the anode materials for SIBs, the yolk-shell nanocages of CoS2/VS4@NC electrode exhibits excellent rate capability and stable cycle performance. Notably, it displays a long-term cycling stability with excellent capacity of 417.28 mA h g-1 after 700 cycles at a high current density of 5 A/g. This developed approach here provides a new route for the design and synthesis of various yolk-shell nanocages nanomaterials from enormous MOFs with multitudinous compositions and morphologies and can be extended to the application into other secondary batteries and energy storage fields.

Preventive Effects of Apple Polyphenol Extract on High-Fat-Diet-Induced Hepatic Steatosis Are Related to the Regulation of Hepatic Lipid Metabolism, Autophagy, and Gut Microbiota in Aged Mice.

Our previous study confirmed that the ameliorated effects of an intervention with an apple polyphenol extract (APE) on hepatic steatosis induced by a high-fat diet (HFD) are dependent on SIRT1. Since SIRT1 expression decreases with age, it remains unclear whether APE intervention is effective against hepatic steatosis in aged mice. Thus, 12-month-old C57BL/6 male mice were fed with an HFD to establish an aging model of hepatic steatosis and treated with 500 mg/(kg·bw·d) APE for 12 weeks. Young mice (two months old) and baseline mice were used as controls to examine the effects of natural aging on hepatic steatosis. Compared with baseline mice, no obvious difference in hepatic histopathological assessment was observed for both young and aged mice on normal diets. Meanwhile, HFD induced much higher nonalcoholic fatty liver disease (NAFLD) activity scores in aged mice than in young mice. APE intervention ameliorated lipid and glucose metabolic disorders and liver injury in HFD-fed aged mice, improved hepatic steatosis, and reduced NAFLD activity scores. The upregulated expressions of SIRT1, HSL, ATG5, Ulk1, and Becn1 and downregulated expressions of HMGCR and FOXO1 suggested improved lipid metabolism and activated autophagy. APE intervention decreased the ratio of Firmicutes/Bacteroidetes and elevated the Akkermansia probiotics abundance. In summary, HFD showed a more significant effect on hepatic steatosis compared to the natural aging process in aged mice, and APE might be a promising dietary ingredient for alleviating hepatic steatosis.

Fucoidan alleviated dextran sulfate sodium-induced ulcerative colitis with improved intestinal barrier, reshaped gut microbiota composition, and promoted autophagy in male C57BL/6 mice.

Although previous research has unveiled the remedial effects of fucoidan, an extract from marine algae, on ulcerative colitis (UC), the precise mechanisms remain elusive. Animal studies have suggested a connection between autophagy and the beneficial influences of fucoidan intervention. We hypothesized that fucoidan's alleviative effects on dextran sulfate sodium (DSS)-induced UC could be ascribed to autophagy. For our study, we chose 36 male C57BL/6 mice and administered 100 or 400 mg/(kg/body weight/day) of fucoidan via gavage for 5 consecutive weeks. During the last week, the mice were given 3% DSS in drinking water to induce UC. In contrast to the DSS-induced UC model, fucoidan intervention prevented DSS-induced body weight loss, mitigated colon shortening, improved colon mucosa damage, enhanced the intestinal barrier, and reduced serum inflammatory factor concentrations. Furthermore, fucoidan intervention reshaped the gut microbiota compositions, increased the relative abundance of Bacteroidota, Muribaculaceae_unclassified, Clostridiales_unclassified, and Lachnospiraceae_NK4A136_group, and decreased the relative abundance of Firmicutes, Proteobacteria, and Escherichia-Shigella, which led to a lower Firmicutes/Bacteroidota ratio. Additionally, fucoidan treatment enhanced autophagy, as evidenced by upregulated protein expressions of BECLIN1, ATG5, ATG7, and an increased microtubule-associated-proteinlight-chain-3-II/microtubule-associated-proteinlight-chain-3-I ratio. Our findings corroborated the ameliorating effects of fucoidan intervention on DSS-induced UC through autophagy activation, reorganization of gut microbiota, and fortification of the intestinal barrier. This lends support to the therapeutic potential of fucoidan as a natural bioactive ingredient for future UC treatments in humans.

Meningitis and sepsis caused by Streptococcus suis in an elderly woman: A CARE-compliant case report.

RATIONALE: Streptococcus suis (S suis)-associated infections are uncommon but life-threatening diseases. The clinical manifestations vary from general symptoms of bacterial infection to fatal meningitis. The clinical manifestation and routine diagnostic testing is not specific enough to obtain well-time diagnosis. PATIENT CONCERNS AND DIAGNOSIS: We report a case of meningitis and sepsis caused by S suis infection. A 70-year-old woman presented to our emergency department with generalized pain. After hospital admission, her condition rapidly deteriorated to fever, intracranial hypertension, and disturbance of consciousness. Examination of the blood and cerebrospinal fluid with metagenomic next-generation sequencing and bacterial cultures revealed S suis infection. INTERVENTIONS AND OUTCOMES: After anti-infection therapy with meropenem and vancomycin, the patient recovered and was discharged from the hospital with no residual effects. LESSONS: Human infections with S suis are extremely rare. If clinicians encounter a patient with fever, disturbance of consciousness, and intracranial hypertension, especially those who have been exposed to raw pork, S suis infection should be considered. Metagenomic next-generation sequencing can be a useful adjunct for the rapid diagnosis of S suis infection and aid in the planning of clinical treatment. Meanwhile, public health awareness is necessary to limit the risk of S suis infection.

Acute Basophilic Leukemia Arising from Chronic Myeloid Leukemia with +8, I(17q)(q10) and der(22)t(9;22) After Imatinib Therapy.

Acute basophilic leukemia (ABL) arising from chronic myeloid leukemia (CML) with abundant mast cells (MCs), coexisting with a complex karyotype is rare. Here, we report an 81-year-old man admitted to our hospital with a history of ABL. He was diagnosed with CML in the chronic phase in January 2018, and Imatinib was used at a daily dose of 400mg. Then, transformation to ABL with abundant MCs in the bone marrow and complex karyotypes including 48,XY, trisomy 8 (+8), isochromosome 17(q10) [i(17)(q10)], and derivative chromosome 22 t(9;22) [der(22)t(9;22)] were discovered simultaneously in January 2022. In conclusion, the increased number of MCs in our case is a reminder that they might play an important role in the prognosis of CML and trigger the development of complex karyotypes. Moreover, this is the first case report of ABL arising from CML with abundant MCs, coexisting with 48,XY, +8, i(17)(q10), and der(22)t(9;22), during Imatinib treatment. Further studies are needed to better characterize this rare condition.

CT for the evaluation of myocardial extracellular volume with MRI as reference: a systematic review and meta-analysis.

OBJECTIVE: Myocardial extracellular volume (ECV) fraction is an important imaging biomarker in clinical decision-making. CT-ECV is a potential alternative to MRI for ECV quantification. We conducted a meta-analysis to comprehensively assess the reliability of CT for ECV quantification with MRI as a reference. METHODS: We systematically searched PubMed, EMBASE, and the Cochrane Library for relevant articles published since the establishment of the database in July 2022. The articles comparing CT-ECV with MRI as a reference were included. Meta-analytic methods were applied to determine the pooled weighted bias, limits of agreement (LOA), and correlation coefficient (r) between CT-ECV and MRI-ECV. RESULTS: Seventeen studies with a total of 459 patients and 2231 myocardial segments were included. The pooled mean difference (MD), LOA, and r for ECV quantification at the per-patient level was (0.07%; 95% LOA: - 0.42 to 0.55%) and 0.89 (95% CI: 0.86-0.91), respectively, while on the per-segment level was (0.44%; 95% LOA: 0.16-0.72%) and 0.84 (95% CI: 0.82-0.85), respectively. The pooled r from studies with the ECViodine method for ECV quantification was significantly higher compared to those with the ECVsub method (0.94 (95% CI: 0.91-0.96) vs. 0.84 (95% CI: 0.80-0.88), respectively, p = 0.03). The pooled r from septal segments was significantly higher than those from non-septal segments (0.88 (95% CI: 0.86-0.90) vs. 0.76 (95% CI: 0.71-0.90), respectively, p = 0.009). CONCLUSION: CT showed a good agreement and excellent correlation with MRI for ECV quantification and is a potentially attractive alternative to MRI. CLINICAL RELEVANCE STATEMENT: The myocardial extracellular volume fraction can be acquired using a CT scan, which is not only a viable alternative to myocardial extracellular volume fraction derived from MRI but is also less time-consuming and costly for patients. KEY POINTS: • Noninvasive CT-ECV is a viable alternative to MRI-ECV for ECV quantification. • CT-ECV using the ECViodine method showed more accurate myocardial ECV quantification than ECVsub. • Septal myocardial segments showed lower measurement variability than non-septal segments for the ECV quantification.

Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population.

Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (Pinteraction = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications.

Estimating the overall fraction of phenotypic variance attributed to high-dimensional predictors measured with error.

In prospective genomic studies (e.g., DNA methylation, metagenomics, and transcriptomics), it is crucial to estimate the overall fraction of phenotypic variance (OFPV) attributed to the high-dimensional genomic variables, a concept similar to heritability analyses in genome-wide association studies (GWAS). Unlike genetic variants in GWAS, these genomic variables are typically measured with error due to technical limitation and temporal instability. While the existing methods developed for GWAS can be used, ignoring measurement error may severely underestimate OFPV and mislead the design of future studies. Assuming that measurement error variances are distributed similarly between causal and noncausal variables, we show that the asymptotic attenuation factor equals to the average intraclass correlation coefficients of all genomic variables, which can be estimated based on a pilot study with repeated measurements. We illustrate the method by estimating the contribution of microbiome taxa to body mass index and multiple allergy traits in the American Gut Project. Finally, we show that measurement error does not cause meaningful bias when estimating the correlation of effect sizes for two traits.

The regulatory role of N6-methyladenosine RNA modification in gastric cancer: Molecular mechanisms and potential therapeutic targets.

N6-methyladenosinen (m6A) methylation is a frequent RNA methylation modification that is regulated by three proteins: "writers", "erasers", and "readers". The m6A modification regulates RNA stability and other mechanisms, including translation, cleavage, and degradation. Interestingly, recent research has linked m6A RNA modification to the occurrence and development of cancers, such as hepatocellular carcinoma and non-small cell lung cancer. This review summarizes the regulatory role of m6A RNA modification in gastric cancer (GC), including targets, the mechanisms of action, and the potential signaling pathways. Our present findings can facilitate our understanding of the significance of m6A RNA modification in GC.

Case report: Evaluation of myocardial microcirculation in patients with breast cancer after anthracycline chemotherapy by using intravoxel incoherent motion imaging.

Introduction: Anthracycline chemotherapy drugs can produce cardiotoxicity in patients with breast cancer, leading to myocardial cell death and fibrosis, further developing into cardiac failure. However, the condition of myocardial microcirculation was unknown in breast cancer after anthracycline chemotherapy. As a result, intravoxel incoherent motion (IVIM) imaging was used to non-invasively observe the condition of myocardial microcirculation in a patient with breast cancer after anthracycline chemotherapy. Case report: A 43-year-old female patient with a right breast lump was reported. Preoperative ultrasound-guided needle biopsy showed invasive carcinoma of the right breast with fibroadenoma. Sentinel lymph node biopsy combined with simplified radical surgery for right breast cancer was performed. Postoperative pathological findings reported breast cancer (pT2N2M0 IIIA). The patient underwent eight sessions of the EC-TH chemotherapy scheme, and the EC and the TH schemes were adopted for the first four sessions and the last four sessions, respectively. During chemotherapy, during which there was the occurrence of Grade II myelosuppression, chest CT and abdomen CT showed no metastasis, and ECG and cardiac ultrasound reports returned to normal. Cardiac cine magnetic resonance and IVIM imaging were performed at the beginning of the first chemotherapy session (baseline) and after the third, fifth, and eighth chemotherapy sessions, respectively. We found that the fast apparent diffusion coefficient (ADCfast) and f parameters appeared to show a downward trend from the baseline to the fifth chemotherapy session, where the IVIMfast values declined from 163 × 10-3 mm2/s to 148 × 10-3 mm2/s and finally to 134 × 10-3 mm2/s and f values declined from 45% to 36% and then to 30%, respectively. ADCfast and f values showed an inclination from the fifth and eighth chemotherapy sessions. Conclusion: Our case report showed that IVIM technology can likely detect non-invasive myocardial microcirculation early and quantitatively after anthracycline chemotherapy in patients with breast cancer. That is, IVIM technology seems to be helpful for cardiovascular risk monitoring and prognosis assessment of myocardial microcirculation in patients with breast cancer after anthracycline chemotherapy.

Restricted Recruitment of NK Cells with Impaired Function Is Caused by HPV-Driven Immunosuppressive Microenvironment of Papillomas in Aggressive Juvenile-Onset Recurrent Respiratory Papillomatosis Patients.

Laryngopharynx epithelium neoplasia induced by HPV6/11 infection in juvenile-onset recurrent respiratory papillomatosis (JO-RRP) causes a great health issue characteristic of frequent relapse and aggressive disease progression. Local cell-mediated immunity shaped by the recruitment and activation of cytotoxic effector cells is critical for viral clearance. In this study, we found that NK cells in the papillomas of aggressive JO-RRP patients, in contrast to massive infiltrated T cells, were scarce in number and impaired in activation and cytotoxicity as they were in peripheral blood. Data from cell infiltration analysis indicated that the migration of NK cell to papilloma was restricted in aggressive JO-RRP patients. Further study showed that the skewed chemokine expression in the papillomas and elevated ICAM-1 expression in hyperplastic epithelia cells favored the T cell but not NK cell recruitment in aggressive JO-RRP patients. In parallel to the increased CD3+ T cells, we observed a dramatical increase in Tregs and Treg-promoting cytokines such as IL-4, IL-10 and TGFß in papillomas of aggressive JO-RRP patients. Our study suggested that likely initialized by the intrinsic change in neoplastic epithelial cells with persistent HPV infection, the aggressive papillomas built an entry barrier for NK cell infiltration and formed an immunosuppressive clump to fend off the immune attack from intra-papillomas NK cells. IMPORTANCE Frequent relapse and aggressive disease progression of juvenile-onset recurrent respiratory papillomatosis (JO-RRP) pose a great challenge to the complete remission of HPV 6/11 related laryngeal neoplasia. Local immune responses in papillomas are more relevant to the disease control considering the locale infected restriction of HPV virus in epitheliums. In our study, the restricted NK cell number and reduced expression of activating NKp30 receptor suggested one possible mechanism underlying impaired NK cell defense ability in aggressive JO-RRP papillomas. Meanwhile, the negative impact of HPV persistent infection on NK cell number and function represented yet another example of a chronic pathogen subverting NK cell behavior, affirming a potentially important role for NK cells in viral containment. Further, the skewed chemokine/cytokine expression in the papillomas and the elevated adhesion molecules expression in hyperplastic epithelia cells provided important clues for understanding blocked infiltration and antiviral dysfunction of NK cells in papilloma.

A multicenter, randomized, open, controlled trial to evaluate the efficacy of Honglilai Vaginal Cream and Premarin Vaginal Cream for Genitourinary Syndrome of Menopause in different subgroups of Chinese postmenopausal women.

AIM: In a randomized, multicenter, open, controlled trial, we compared the effects of Honglilai Vaginal Cream and Premarin Vaginal Cream in different age subgroups and menopausal year subgroups (trial registration numbers: 02003L00493). METHODS: Postmenopausal women with Genitourinary Syndrome of Menopause (GSM) were divided into Honglilai group (n = 319) and Premarin group (n = 116), while subgroups were divided according to their different characteristics of age and menopausal years. Honglilai Vaginal Cream (0.625 mg/g) or Premarin Vaginal Cream (0.625 mg/g) once daily for 3 weeks. RESULTS: In the subgroup of participates >60 years, there were no significant differences of Vaginal Cell Maturation Index (VMI) between the two groups after treatment (p = .171). In the subgroup of 50-59 years, the VMI of Honglilai group was significantly lower than Premarin group (Honglilai group: 74.37 ± 22.76; Premarin group: 80.06 ± 16.15; p = .02). There were no significant differences of Vaginal symptom scores between Honglilai group and Premarin group in every sub-group (p > .05). CONCLUSIONS: Honglilai Vaginal Cream had comparable efficacy with Premarin Vaginal Cream in Chinese women older than 60 years.

The Oral Microbiome and Lung Cancer Risk: An Analysis of 3 Prospective Cohort Studies.

BACKGROUND: Previous studies suggested associations between the oral microbiome and lung cancer, but studies were predominantly cross-sectional and underpowered. METHODS: Using a case-cohort design, 1306 incident lung cancer cases were identified in the Agricultural Health Study; National Institutes of Health-AARP Diet and Health Study; and Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Referent subcohorts were randomly selected by strata of age, sex, and smoking history. DNA was extracted from oral wash specimens using the DSP DNA Virus Pathogen kit, the 16S rRNA gene V4 region was amplified and sequenced, and bioinformatics were conducted using QIIME 2. Hazard ratios and 95% confidence intervals were calculated using weighted Cox proportional hazards models. RESULTS: Higher alpha diversity was associated with lower lung cancer risk (Shannon index hazard ratio = 0.90, 95% confidence interval = 0.84 to 0.96). Specific principal component vectors of the microbial communities were also statistically significantly associated with lung cancer risk. After multiple testing adjustment, greater relative abundance of 3 genera and presence of 1 genus were associated with greater lung cancer risk, whereas presence of 3 genera were associated with lower risk. For example, every SD increase in Streptococcus abundance was associated with 1.14 times the risk of lung cancer (95% confidence interval = 1.06 to 1.22). Associations were strongest among squamous cell carcinoma cases and former smokers. CONCLUSIONS: Multiple oral microbial measures were prospectively associated with lung cancer risk in 3 US cohort studies, with associations varying by smoking history and histologic subtype. The oral microbiome may offer new opportunities for lung cancer prevention.

Daytime restricted feeding promotes circadian desynchrony and metabolic disruption with changes in bile acids profiles and gut microbiota in C57BL/6 Male Mice.

Fasting/feeding cycles regulate clock-lipid-bile acid (BA) metabolic homeostasis, and gut microbiota also participates in connecting circadian rhythms with BA metabolism. To investigate the cyclical nature of microbial-metabolism-host interactions, sixty male C57BL/6 mice were randomized into three feeding regimens with a chow diet: 24 h ad libitum (AC), 12 h nighttime feeding (NC) or 12 h daytime feeding (DC). Five weeks later, the mice were sacrificed at six-hour intervals over 24 hours. Daytime feeding abolished hepatic rhythmic expressions of Per1, Cry1/2 and Rev-erbα or changed the acrophase of Clock, Bmal1 and Per2, also the rhythmic expression of genes Hsl, Fas, Acc, Srebp-1c in lipid homeostasis and Cyp7a1, Cyp7b1, Cyp8b1, Lrh-1 and Shp in bile acid metabolism compared with their ad libitum and dark-fed companions. Furthermore, daytime feeding upregulated the levels of fecal primary BA, secondary BA and unconjugated BA at ZT0 and decreased their levels at ZT12. Meanwhile, daytime feeding altered the diversity of gut microbiota and microbiota compositions, with obviously higher abundance of Firmicutes and F/B ratio, and significantly lower abundance of Verrucomicrobia, as well as altered fluctuations of Akkermansia, Lactobacillus and Parabacteroides. In conclusion, shifting food intake to the rest phase caused a desynchronization in the liver between circadian rhythm and metabolism, as well as abnormal circadian variations in fecal BA profiles and gut microbiota.

The Ameliorating Effects of Apple Polyphenol Extract on High-Fat-Diet-Induced Hepatic Steatosis Are SIRT1-Dependent: Evidence from Hepatic-Specific SIRT1 Heterozygous Mutant C57BL/6 Mice.

Apple polyphenol extract (APE) has been reported to possess protective effects against hepatic steatosis. To explore whether APE-induced alleviation of hepatic steatosis is SIRT1-dependent, the present study was carried out using wild-type and hepatic SIRT1 heterozygous mutant (Sirt1+/-) C57BL/6 mice. On consideration of the sex disparity related to hepatic steatosis morbidity, both male and female mice were included in the study. Six to eight week old mice were fed a high-fat diet (HFD) and randomly assigned to one of the following groups: (1) wild-type mice (wt+HFD), (2) Sirt1+/- mice (Sirt1+/-+HFD), and (3) Sirt1+/- mice with 500 mg/(kg·bw·d) APE intragastric administration (Sirt1+/-+HAP). HFD-induced weight gain and triglyceride accumulation was more prominent in Sirt1+/- mice in comparison to wild-type mice. Following APE treatment, these effects were significantly reduced along with the alleviation of hepatic steatosis via upregulated expression of SIRT1 at the protein and mRNA levels in both male and female mice. However, APE differentially regulated the genes related to lipid metabolism (Lkb1, Ampk, Hsl, Srebp-1c, Abcg1, and Cd36) in a sex-specific manner. Moreover, APE treatment altered gut microbiota composition, with an increased relative abundance of Akkermansia and a decreased Firmicutes/Bacterodetes ratio. Thus, our study provided new evidence supporting our hypothesis that APE-induced alleviation of hepatic steatosis is SIRT1-dependent.

Cancer stem cell regulated phenotypic plasticity protects metastasized cancer cells from ferroptosis.

Cancer cells display phenotypic equilibrium between the stem-like and differentiated states during neoplastic homeostasis. The functional and mechanistic implications of this subpopulation plasticity remain largely unknown. Herein, it is demonstrated that the breast cancer stem cell (BCSC) secretome autonomously compresses the stem cell population. Co-implantation with BCSCs decreases the tumor-initiating capacity yet increases metastasis of accompanying cancer cells, wherein DKK1 is identified as a pivotal factor secreted by BCSCs for such functions. DKK1-promotes differentiation is indispensable for disseminated tumor cell metastatic outgrowth. In contrast, DKK1 inhibitors substantially relieve the metastatic burden by restraining metastatic cells in the dormant state. DKK1 increases the expression of SLC7A11 to protect metastasizing cancer cells from lipid peroxidation and ferroptosis. Combined treatment with a ferroptosis inducer and a DKK1 inhibitor exhibits synergistic effects in diminishing metastasis. Hence, this study deciphers the contribution of CSC-regulated phenotypic plasticity in metastatic colonization and provides therapeutic approaches to limit metastatic outgrowth.

Apple polyphenol extract modulates bile acid metabolism and gut microbiota by regulating the circadian rhythms in daytime-restricted high fat diet feeding C57BL/6 male mice.

The homeostasis of circadian clock linked to bile acid (BA) metabolism and gut microbiota has profound benefits in maintaining the health status of the host. The aim of this study was to investigate the prevention and regulation of apple polyphenol extract (APE) on BA metabolism and gut microbiota by means of modulation of circadian rhythms in mice. Eighty male C57BL/6 mice were randomized into four groups: 24-hour ad libitum standard chow group (AC), ad libitum HFD group (AF), restricted 12 h daytime HFD feeding group (DF), and daytime HFD feeding with APE treatment group (DP). Five weeks later, the mice were sacrificed at 6 h intervals over a 24 h period. The results showed that APE decreased body weight and induced daily rhythms of Cry1 and Rorα in the suprachiasmatic nucleus (SCN) and Clock, Cry1 and Cry2 in the ileum in daytime HFD mice. APE significantly increased the expression of hepatic FXR at ZT0 and BSEP at ZT12 and inhibited the expression of ileac FXR at ZT12, reduced levels of fecal TBAs, secondary BAs, and unconjugated BAs at ZT0. Meanwhile, APE regulated the diversity and composition of the gut microbiota, and increased the abundance of probiotics. Therefore, our work revealed that APE as a clock-regulating natural compound could modulate BA metabolism and gut microbiota and protect against circadian disruption in a clock-dependent manner.

A review of the risk factors associated with juvenile-onset recurrent respiratory papillomatosis: genetic, immune and clinical aspects.

BACKGROUND: Juvenile-onset recurrent respiratory papillomatosis (JoRRP) is one of the most common benign lesions of hyperplastic respiratory epithelial tissue in children and is predominantly caused by human papillomaviruses (HPVs) 6 and 11. The clinical course of the disease is variable, and some patients even develop a malignancy. The purpose of this review was to summarize the related factors affecting the disease course in patients with JoRRP. DATA SOURCES: We used databases, including PubMed and Google Scholar, to search for publications on factors associated with the genetic, immune, and clinical aspects of JoRRP. The most relevant articles to the scope of this review were chosen for analysis. RESULTS: Mother-to-child transmission is the most important mode of disease transmission; other factors, such as immune condition or genetic susceptibility, may be important determinants of JoRRP occurrence. Genetically, the presence of DRB1*0301 and HPV 6/11 E6/E7 is associated with a more severe disease. Immunewise, patients have an enhanced T helper 2-like response. In addition, regulatory T cells are enriched in tumors and may become one of the effective prognostic indicators. For clinical characteristics, patients infected with HPV-11 have more aggressive disease. However, compared with HPV type, age at first onset is a more important factor related to the aggressiveness of JoRRP. Furthermore, socioeconomic status may also affect the course. CONCLUSIONS: Genetic, immune, and some clinical factors have been noted to play an important role in the course of JoRRP. Exploring definite influencing factors will be an important direction of research in the future.

fast.adonis: a computationally efficient non-parametric multivariate analysis of microbiome data for large-scale studies.

Motivation: Nonparametric multivariate analysis has been widely used to identify variables associated with a dissimilarity matrix and to quantify their contribution. For very large studies ( n ≥ 5000 ) and many explanatory variables, existing software packages (e.g. adonis and adonis2 in vegan) are computationally intensive when conducting sequential multivariate analysis with permutations or bootstrapping. Moreover, for subjects from a complex sampling design, we need to adjust for sampling weights to derive an unbiased estimate. Results: We implemented an R function fast.adonis to overcome these computational challenges in large-scale studies. fast.adonis generates results consistent with adonis/adonis2 but much faster. For complex sampling studies, fast.adonis integrates sampling weights algebraically to mimic the source population; thus, analysis can be completed very fast without requiring a large amount of memory. Availability and implementation: fast.adonis is implemented using R and is publicly available at https://github.com/jennylsl/fast.adonis. Supplementary information: Supplementary data are available at Bioinformatics Advances online.