Single-cell RNA sequencing reveals that an imbalance in monocyte subsets rather than changes in gene expression patterns is a feature of postmenopausal osteoporosis.

The role of monocytes in postmenopausal osteoporosis is widely recognized; however, the mechanisms underlying monocyte reprogramming remain unknown. In this study, single-cell RNA sequencing (scRNA-seq) was conducted on CD14+ bone marrow monocytes obtained from three postmenopausal women with normal bone mineral density (BMD) and three women with postmenopausal osteoporosis (PMOP). Monocle2 was used to classify the monocytes into 7 distinct clusters. The proportion of Cluster 1 significantly decreased in PMOP patients, while the proportion of Cluster 7 increased. Further analysis via GSEA, transcription factor activity analysis, and sc-metabolic analysis revealed significant differences between Clusters 1 and 7. Cluster 7 exhibited upregulated pathways associated with inflammation, immunity, and osteoclast differentiation, whereas Cluster 1 demonstrated the opposite results. Monocle2, TSCAN, VECTOR and scVelo data indicated that Cluster 1 represented the initial subset and that Cluster 7 represents one of the terminal subsets. BayesPrism and ssGSEA were employed to analyze the bulk transcriptome data obtained from the GEO database. The observed alterations in the proportions of Clusters 1 and 7 were validated and found to have diagnostic significance. CD16 serves as the marker gene for Cluster 7, thus leading to an increased proportion of CD16+ monocytes in women with PMOP. Flow cytometry was used to assess the consistency of outcomes with those of the bioinformatic analysis. Subsequently, an additional scRNA-seq analysis was conducted on bone marrow mononuclear cells obtained from three patients with PMOP and three postmenopausal women with normal BMD. The differential proportions of Cluster 1 and Cluster 7 were once again confirmed, with the pathological effect of Cluster 7 may attribute to cell-cell communication. The scRNA-seq findings suggest that an imbalance in monocyte subsets is a characteristic feature of PMOP. These findings elucidate the limitations of utilizing bulk transcriptome data for detecting alterations in monocytes, which may influence novel research inquiries.

Monocytes are a type of white blood cell that plays a role in postmenopausal osteoporosis (PMOP), a condition where bones become weak and brittle after menopause. However, how monocytes change in this condition is not fully understood. In this study, single-cell RNA sequencing was used to analyze bone marrow monocytes from postmenopausal women with normal bone density and those with osteoporosis. Two distinct types of monocytes were identified, which were called Clusters 1 and 7. In women with PMOP, there was a decrease in Cluster 1 monocytes and an increase in Cluster 7 monocytes. This change was validated in external data sets and in peripheral blood. Further analysis showed that Cluster 7 monocytes positively correlated with inflammation, immunity, and osteoclast differentiation (a process that leads to bone resorption). Cluster 1 monocytes were found to be the initial subset, while Cluster 7 monocytes were one of the terminal subsets. Overall, this study suggests that an imbalance in monocyte subsets is a characteristic feature of postmenopausal osteoporosis. These findings have important implications for understanding the role of monocytes in bone health.

Effects of sleep disturbance, cancer-related fatigue, and psychological distress on breast cancer patients' quality of life: a prospective longitudinal observational study.

More attention has gone to researching the cancer-related fatigue (CRF)-sleep disturbance (SD)-psychological distress (PD) symptom cluster in breast cancer patients during the chemotherapy period, but the change trend and heterogeneous development track in the whole treatment stage remain unclear, and it is also unclear whether the appearance of and changes in one symptom cause changes in other symptoms and quality of life (QoL). This study, using breast cancer patients' data collected through a validated questionnaire, examined the relationships between SD, CRF, PD, and QoL using latent growth modeling analyses. CRF developmental trajectories showed an upward trend over five surveys (slope = 0.649, P < 0.001); PD showed a significant weakening trend (slope = - 0.583, P < 0.001); SD showed an increasing trend (slope = 0.345, P < 0.001), and QoL showed a statistically significant weakening trend (slope = - 0.373, P < 0.001). The initial CRF (coefficient = - 0.233, P < 0.01), PD (coefficient = - 0.296, P < 0.01), and SD (coefficient = - 0.388, P < 0.001) levels had a statistically significant negative effect on initial QoL level. The linear development rate of PD was statistically significant and negatively affected that of QoL (coefficient = - 0.305, P < 0.05), whereas the quadratic development rate of SD negatively affected that of QoL (coefficient = - 0.391, P < 0.05). Medical staff should identify the change characteristics of different variables based on SD, CRF, PD, and QoL change trajectories, and advance the intervention time, as changes in variables affect other variables' subsequent changes.

Activation of Piezo1 increases the sensitivity of breast cancer to hyperthermia therapy.

Photothermal therapy (PTT) of nanomaterials is an emerging novel therapeutic strategy for breast cancer. However, there exists an urgent need for appropriate strategies to enhance the antitumor efficacy of PTT and minimize damage to surrounding normal tissues. Piezo1 might be a promising novel photothermal therapeutic target for breast cancer. This study aims to explore the potential role of Piezo1 activation in the hyperthermia therapy of breast cancer cells and investigate the underlying mechanisms. Results showed that the specific agonist of Piezo1 ion channel (Yoda1) aggravated the cell death of breast cancer cells triggered by heat stress in vitro. Reactive oxygen species (ROS) production was significantly increased following heat stress, and Yoda1 exacerbated the rise in ROS release. GSK2795039, an inhibitor of NADPH oxidase 2 (NOX2), reversed the Yoda1-mediated aggravation of cellular injury and ROS generation after heat stress. The in vivo experiments demonstrate the well photothermal conversion efficiency of TiCN under the 1,064 nm laser irradiation, and Yoda1 increases the sensitivity of breast tumors to PTT in the presence of TiCN. Our study reveals that Piezo1 activation might serve as a photothermal sensitizer for PTT, which may develop as a promising therapeutic strategy for breast cancer.

PI3K/AKT mediated De novo fatty acid synthesis regulates RIG-1/MDA-5-dependent type I IFN responses in BVDV-infected CD8+T cells.

Bovine viral diarrhea virus (BVDV) has caused massive economic losses in the cattle business worldwide. Fatty acid synthase (FASN), a key enzyme of the fatty acid synthesis (FAS) pathway, has been shown to support virus replication. To investigate the role of fatty acids (FAs) in BVDV infection, we infected CD8+T lymphocytes obtained from healthy cattle with BVDV in vitro. During early cytopathic (CP) and noncytopathic (NCP) BVDV infection in CD8+ T cells, there is an increase in de novo lipid biosynthesis, resulting in elevated levels of free fatty acids (FFAs) and triglycerides (TG). BVDV infection promotes de novo lipid biosynthesis in a dose-dependent manner. Treatment with the FASN inhibitor C75 significantly reduces the phosphorylation of PI3K and AKT in BVDV-infected CD8+ T cells, while inhibition of PI3K with LY294002 decreases FASN expression. Both CP and NCP BVDV strains promote de novo fatty acid synthesis by activating the PI3K/AKT pathway. Further investigation shows that pharmacological inhibitors targeting FASN and PI3K concurrently reduce FFAs, TG levels, and ATP production, effectively inhibiting BVDV replication. Conversely, the in vitro supplementation of oleic acid (OA) to replace fatty acids successfully restored BVDV replication, underscoring the impact of abnormal de novo fatty acid metabolism on BVDV replication. Intriguingly, during BVDV infection of CD8+T cells, the use of FASN inhibitors prompted the production of IFN-α and IFN-ß, as well as the expression of interferon-stimulated genes (ISGs). Moreover, FASN inhibitors induce TBK-1 phosphorylation through the activation of RIG-1 and MDA-5, subsequently activating IRF-3 and ultimately enhancing the IFN-1 response. In conclusion, our study demonstrates that BVDV infection activates the PI3K/AKT pathway to boost de novo fatty acid synthesis, and inhibition of FASN suppresses BVDV replication by activating the RIG-1/MDA-5-dependent IFN response.

Incidence and risk factors for psychological distress in adult female patients with breast cancer: a systematic review and meta-analysis.

Introduction: Cancer-related distress can be described as a complex and unpleasant combination of psychological (such as cognitive, behavioral, and emotional), social, and spiritual challenges that may impact an individual's ability to effectively cope with the physical symptoms of cancer and its treatment. Existing literature has confirmed psychological distress (PD) as an important sequela of breast cancer diagnosis and treatment. However, the incidence and risk factors for PD in adult female patients with breast cancer remain unclear; therefore, focusing on the PD of female breast cancer patients is meaningful, as they are at highest risk of contracting breast cancer, and might differ in their coping styles from men. Objective: This review aimed to identify the incidence and risk factors for PD in adult woman patients with breast cancer, and to help guide targeted intervention to prevent distress. Method: PubMed, Embase, Cochrane Library, CINAL, PsycINFO, China Knowledge Resource Integrated Database, Wanfang Database, the Chinese Biomedical Database, and Weipu Database were searched for data regarding the incidence and risk factors of PD in adult women with breast cancer. Results: The prevalence of PD, assessed using the distress thermometer, ranged between 11.2%-86.7%, and a meta-analysis of 47 studies with 15,157 adult female breast cancer patients showed that the pooled prevalence was 52.0%. Further, this study identified 40 risk factors. However, owing to the inclusion of at least two studies for a certain risk factor, 10 risk factors were merged for the meta-analysis. Independent risk factors included higher education level, late-stage tumor, emotional concerns, no medical insurance, modified radical mastectomy, and history of depression; age and neuroticism were not associated with PD; and higher monthly income was revealed as a protective factor against it. Conclusion: The incidence of PD in female patients with breast cancer is high and it involves 10 risk factors, though some are controversial owing to insufficient evidence. Further research is needed to explore the underlying mechanisms of PD and develop risk factor-based holistic intervention programs to reduce its incidence. Systematic review registration: The protocol of this study has been registered in the database PROSPERO (registration ID: CRD42023433578).

Co-exposure to 55 endocrine-disrupting chemicals linking diminished sperm quality: Mixture effect, and the role of seminal plasma docosapentaenoic acid.

Isolated effects of single endocrine-disrupting chemicals (EDCs) on male reproductive health have been studied extensively, but their mixture effect remains unelucidated. Previous research has suggested that consuming diet enriched in omega-3 polyunsaturated fatty acids (PUFA) might be beneficial for reproductive health, whether omega-3 PUFA could moderate the effect of EDCs mixture on semen quality remains to be explored. In this study of 155 male recruited from a reproductive health center in China, we used targeted-exposomics to simultaneously measure 55 EDCs in the urine for exposure burden. Regression analyses were restricted to highly detected EDCs (≥55%, n = 34), and those with consistently elevated risk were further screened and brought into mixture effect models (Bisphenol A, ethyl paraben, methyl paraben [MeP], benzophenone-1 [BP1], benzophenone-3, mono(3-carboxypropyl) phthalate [MCPP]). Bayesian Kernel Machine Regression (BKMR) and quantile-based g-computation (QGC) models demonstrated that co-exposure to top-ranked EDCs was related to reduced sperm total (ß = -0.18, 95%CI: -0.29 - -0.07, P = 0.002) and progressive motility (ß = -0.27, 95%CI: -0.43 - -0.10, P = 0.002), but not to lower semen volume. BP1, MeP and MCPP were identified as the main effect driver for deteriorated sperm motion parameters using mixture model analyses. Seminal plasma fatty acid profiling showed that high omega-3 PUFA status, notably elevated docosapentaenoic acid (DPA, C22:5n-3) status, moderated the association between MCPP and sperm motion parameters (total motility: ß = 0.26, 95%CI: 0.01 - -0.51, Pinteraction = 0.047; progressive motility: ß = 0.64, 95%CI: 0.23 - 1.05, Pinteraction = 0.003). Co-exposure to a range of EDCs is mainly associated with deteriorated sperm quality, but to a lesser extent on sperm quantity, high seminal plasma DPA status might be protective against the effect. Our work emphasizes the importance of exposomic approach to assess chemical exposures and highlighted a new possible intervention target for mitigating the potential adverse effect of EDCs on semen quality.

MOINER: A Novel Multiomics Early Integration Framework for Biomedical Classification and Biomarker Discovery.

In the context of precision medicine, multiomics data integration provides a comprehensive understanding of underlying biological processes and is critical for disease diagnosis and biomarker discovery. One commonly used integration method is early integration through concatenation of multiple dimensionally reduced omics matrices due to its simplicity and ease of implementation. However, this approach is seriously limited by information loss and lack of latent feature interaction. Herein, a novel multiomics early integration framework (MOINER) based on information enhancement and image representation learning is thus presented to address the challenges. MOINER employs the self-attention mechanism to capture the intrinsic correlations of omics-features, which make it significantly outperform the existing state-of-the-art methods for multiomics data integration. Moreover, visualizing the attention embedding and identifying potential biomarkers offer interpretable insights into the prediction results. All source codes and model for MOINER are freely available https://github.com/idrblab/MOINER.

Investigating fear of cancer recurrence among female breast cancer survivors and their spouses in southwest China: a cross-sectional study.

OBJECTIVES: Examining fear of cancer recurrence (FCR) among breast cancer survivors and their spouses, and the protective effect of family resilience on FCR among couples affected by breast cancer. DESIGN: Cross-sectional survey design. SETTING: Ten general grade IIIa (>500 beds) hospitals in southwest China. PARTICIPANTS: Overall, 392 early breast cancer survivors and their spousal caregivers (N=392) were recruited from cancer centres in hospitals. PRIMARY AND SECONDARY OUTCOME MEASURES: Spouses' and survivors' FCR were the primary outcome measures. Family resilience and perceived stress were the secondary outcome measures. Using a convenience sampling method, we collected data on-site using paper questionnaires. The Chinese version of the Family Resilience Assessment Scale, Perceived Stress Scale, Fear of Progression Questionnaire Short Form and Fear of Progression Questionnaire-Short Form for spouses were used to evaluate the outcomes. RESULTS: The model accounted for 66.3% and 53.6% of the variance in spouses' FCR and survivors' FCR, respectively. Family resilience directly negatively affected perceived stress and spouses' and survivors' FCR (ß=-0.22; ß=-0.13; ß=-0.19). Perceived stress was a partial mediator of the association between family resilience and survivors' FCR (ß=-0.070; 95% CI :-0.151 to -0.022). Spouses' FCR partially mediated the association between family resilience and survivors' FCR (ß=-0.048; 95% CI= -0.092 to -0.015). Perceived stress and spouses' FCR played a significant chain-mediated role between family resilience and survivors' FCR (ß=-0.061; 95% CI: -0.119 to -0.022). CONCLUSIONS: Family-centred approaches to reducing survivors' perceived stress can improve the psychological well-being of couples affected by breast cancer and ultimately reduce FCR. Medical staff should consider the psychological feelings of survivors and their spousal caregivers when devising the intervention plan, which should address the families' potential and mobilise family and community resources for increasing family resilience.

PFASs in Cerebrospinal Fluids and Blood-CSF Barrier Permeability in Patients with Cognitive Impairment.

Attention has been drawn to the associations between PFASs and human cognitive decline. However, knowledge on the occurrence and permeability of PFASs in the brains of patients with cognitive impairment has not been reported. Here, we determined 30 PFASs in paired sera and cerebrospinal fluids (CSFs) from patients with cognitive impairment (n = 41) and controls without cognitive decline (n = 18). We revealed similar serum PFAS levels but different CSF PFAS levels, with lower CSF PFOA (median: 0.125 vs 0.303 ng/mL, p < 0.05), yet higher CSF PFOS (0.100 vs 0.052 ng/mL, p < 0.05) in patients than in controls. Blood-brain transfer rates also showed lower RCSF/Serum values for PFOA and higher RCSF/Serum values for PFOS in patients, implying potential heterogeneous associations with cognitive function. The RCSF/Serum values for C4-C14 perfluoroalkyl carboxylates exhibited a U-shape trend with increasing chain length. Logistic regression analyses demonstrated that CSF PFOS levels were linked to the heightened risk of cognitive impairment [odds ratio: 3.22 (1.18-11.8)] but not for serum PFOS. Toxicity inference results based on the Comparative Toxicogenomics Database suggested that PFOS in CSF may have a greater potential to impair human cognition than other PFASs. Our results contribute to a better understanding of brain PFAS exposure and its potential impact on cognitive function.

Linker substitution influences succinimide ring hydrolysis equilibrium impacting the stability of attachment to antibody-drug conjugates.

Maleimide chemistry is widely used in antibody-drug conjugate (ADC) generation to connect drugs to antibodies through a succinimide linker. The resulting ADC is prone to payload loss via a reverse Michael reaction, leading to premature drug release in vivo. Complete succinimide hydrolysis is an effective strategy to overcome the instability of ADC. However, we discovered through previous work that hydrolysed succinimide rings can close again in a liquid formulation during storage and under thermal stress conditions. In this work, a set of maleimide linkers with hydrolysis-prone groups were designed. The corresponding ADCs were prepared and subjected to thermal stress conditions. The extent of succinimide hydrolysis and drug release was measured, and ADC properties such as SEC, DAR, pI and clog P of linkers were calculated. Our results demonstrated that even though all these groups increased the hydrolysis rate, they have different impacts on maintaining the hydrolysed succinimide ring in an open conformation and ADC stability in a liquid formulation.

Environmentally realistic dose of tire-derived metabolite 6PPD-Q exposure causes intestinal jejunum and ileum damage in mice via cannabinoid receptor-activated inflammation.

N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone (6PPD-Q) is a quinone derivative of a common tire additive 6PPD, whose occurrence has been widely reported both in the environment and human bodies including in adults, pregnant women and children. Yet, knowledge on the potential intestinal toxicity of 6PPD-Q in mammals at environmentally relevant dose remain unknown. In this study, the effects of 6PPD-Q on the intestines of adult ICR mice were evaluated by orally administering environmentally relevant dose or lower levels of 6PPD-Q (0.1, 1, 10, and 100 µg/kg) for 21 days. We found that 6PPD-Q disrupted the integrity of the intestinal barrier, mostly in the jejunum and ileum, but not in the duodenum or colon, in a dose-dependent manner. Moreover, intestinal inflammation manifested with elevated levels of TNF-α, IL-1, and IL-6 mostly observed in doses at 10 and 100 µg/kg. Using reverse target screening technology combining molecular dynamic simulation modeling we identified key cannabinoid receptors including CNR2 activation to be potentially mediating the intestinal inflammation induced by 6PPD-Q. In summary, this study provides novel insights into the toxic effects of emerging contaminant 6PPD-Q on mammalian intestines and that the chemical may be a cannabinoid receptor agonist to modulate inflammation.

AnnoPRO: a strategy for protein function annotation based on multi-scale protein representation and a hybrid deep learning of dual-path encoding.

Protein function annotation has been one of the longstanding issues in biological sciences, and various computational methods have been developed. However, the existing methods suffer from a serious long-tail problem, with a large number of GO families containing few annotated proteins. Herein, an innovative strategy named AnnoPRO was therefore constructed by enabling sequence-based multi-scale protein representation, dual-path protein encoding using pre-training, and function annotation by long short-term memory-based decoding. A variety of case studies based on different benchmarks were conducted, which confirmed the superior performance of AnnoPRO among available methods. Source code and models have been made freely available at: https://github.com/idrblab/AnnoPRO and https://zenodo.org/records/10012272.

Crucial computed tomography and magnetic resonance imaging findings of fallopian tubal tuberculosis for diagnosis: a retrospective study of 26 cases.

Background: Fallopian tubal tuberculosis (FTTB), which typically presents with non-specific clinical symptoms and mimics ovarian malignancies clinically and radiologically, often affects young reproductive females and can lead to infertility if not promptly managed. Early diagnosis by imaging modalities is crucial for initiating timely anti-tuberculosis (anti-TB) treatment. Currently, comprehensive radiological descriptions of this relatively rare disease are limited. We aimed to comprehensively investigate the computed tomography (CT) and magnetic resonance imaging (MRI) characteristics of FTTB in patients from the Kashi area, which has the highest incidence of TB in China, to extend radiologists' understanding of this disease. Methods: We conducted a retrospective cross-sectional study of 26 patients diagnosed with FTTB at the First People's Hospital of Kashi Area. All the patients underwent abdominal and pelvic contrast-enhanced CT examinations and/or pelvic contrast-enhanced MRI from January 2017 to June 2022. The imaging findings were evaluated in consensus by two experienced radiologists specialized in abdominal and pelvic imaging. The evaluated sites included the fallopian tubes, ovaries, peritoneum, mesentery, retroperitoneal nodes, and parailiac nodes. The patient characteristics are reported using descriptive statistics. The patient imaging results are presented as percentages. The normally distributed continuous variables are reported as the mean ± standard deviation (SD), and otherwise as the median with the interquartile range (IQR). Results: The median age of the patients was 27 years (IQR: 25-34 years). Bilateral involvement of the fallopian tubes was observed in all patients. The tubal wall appeared coarse with tiny intraductal nodules in 96% (25 of 26) of the patients. The mean CT value of the tubal contents was 34 Hounsfield units (HUs; SD: 3.3 HUs). Ascites was present in 92% (24 of 26) of the patients, with 20 patients showing encapsulated effusion. Among these patients, 20 exhibited the highest CT values of ascites (>20 HUs). Linear enhancement of the parietal peritoneum was observed in 88% (23 of 26) of the patients, of whom 22 had peritoneal nodules measuring a median diameter of 0.4 cm (IQR: 0.3-0.6 cm). Eight patients had retroperitoneal and parailiac nodal enlargement, of whom two showed nodal necrosis, and none displayed nodal calcification. Conclusions: FTTB is consistently accompanied by tuberculous peritonitis. FTTB typically presents with tubal dilation, and coarseness and nodules in the lumen, as well as intraductal caseous material and calcification. Tuberculous peritonitis exhibits high-density ascites, peritoneal adhesion, linear enhancement of the parietal peritoneum, and tiny peritoneal nodules. The co-occurrence of these features strongly suggests a diagnosis of FTTB.

ROS/MMP-9 mediated CS degradation in BMSC inhibits citric acid metabolism participating in the dual regulation of bone remodelling.

It is necessary to figure out the abnormal energy metabolites at the cellular level of postmenopausal osteoporosis (PMOP) bone microenvironment. In this study, we constructed PMOP model by ovariectomy and identified 9 differential metabolites compared with control femur by energy metabolomic. The enrichment analysis of differential metabolites revealed that tricarboxylic acid cycle, glucagon pathway and purinergic signaling pathway were the main abnormal metabolic processes. Citric acid was identified as the key metabolite by constructing compound reaction-enzyme-gene network. The functional annotation of citric acid targets identified by network pharmacological tools indicated that matrix metalloproteinase 9 (MMP-9) may be involved in regulating citric acid metabolism in the osteogenic differentiation of bone marrow mesenchymal stem cell (BMSC). Molecular docking shows that the interaction forces between MMP-9 and citric acid synthase (CS) is -638, and there are multiple groups of residues used to form hydrogen bonds. Exogenous H2O2 promotes the expression of MMP-9 in BMSC to further degrade CS resulting in a decrease in mitochondrial citric acid synthesis, which leads to the disorder of bone remodeling by two underlying mechanisms ((1) the decreased histone acetylation inhibits the osteogenic differentiation potential of BMSC; (2) the decreased bone mineralization by citric acid deposition). MMP-9-specific inhibitor (MMP-9-IN-1) could significantly improve the amount of CS in BMSC to promote cellular citric acid synthesis, and further enhance bone remodeling. These findings suggest inhibiting the degradation of CS by MMP-9 to promote the net production of citric acid in osteogenic differentiation of BMSC may be a new direction of PMOP research.

Enrichment of polycyclic aromatic hydrocarbon metabolizing microorganisms on the oral mucosa of tobacco users.

Certain soil microbes resist and metabolize polycyclic aromatic hydrocarbons (PAHs). The same is true for a subset of skin microbes. In the human mouth, oral microbes have the potential to oxidize tobacco PAHs, thereby increasing these chemicals' ability to cause cancer of adjacent epithelium. We hypothesized that we could identify, in smokers, the oral mucosal microbes that can metabolize PAH. We isolated bacteria and fungi that survived long-term in minimal media with PAHs as the sole carbon source, under aerobic conditions, from the oral mucosa in 17 of 26 smokers and two of 14 nonsmokers. Of bacteria genera that survived harsh PAH exposure in vitro, most were found at trace levels, except for Staphylococcus, Actinomyces, and Kingella, which were more abundant. Two PAH-resistant strains of Candida albicans (C. albicans) were isolated from smokers. C. albicans was a prime candidate to contribute to carcinogenesis in tobacco users as it is found orally at high levels in tobacco users on the mucosa, and some Candida species can metabolize PAHs. However, when C. albicans isolates were tested for metabolism of two model PAH substrates, pyrene and phenanthrene, they were not capable, suggesting they cannot metabolize PAH under the conditions used. In conclusion, evidence for large scale microbial degradation of tobacco PAHs under aerobic conditions on the oral mucosa remains lacking, though nonabundant PAH metabolizers are certainly present.

Human milk oligosaccharides and the association with microbiota in colostrum: a pilot study.

HMOs (Human milk oligosaccharide) has an impact on maternal and infant health. Colostrum samples of 70 breastfeeding women in China were collected and recorded clinical characteristics. The major oligosaccharides and microbiota were quantitated in colostrum. The concentration of fucosylated HMOs in primipara was higher than that of multipara (p = 0.030). The concentration of N-acetylated HMOs in vaginal delivery milk was less than that of cesarean (p = 0.038). Non-fucosylated HMOs of breastfeeding women were less than that of breast pump (p = 0.038). Meanwhile, the concentration of LNT was positively correlated with Lactobacillus (r = 0.250, p = 0.037). DS-LNT was negatively correlated with Staphylococcus (r = - 0.240, p = 0.045). There was a positive correlation of Streptococcus with LNFP II (r = 0.314, p = 0.011) and 3-SL (r = 0.322, p = 0.009). In addition, there was a negative correlation between 2'-FL and 3-FL (r = - 0.465, p = 0.001). There was a positive correlation between LNT and LNnT (r = 0.778, p = 0.001). Therefore, the concentration of HMOs is related to number of deliveries, delivery mode, lactation mode and perinatal antibiotic. The concentration of HMOs is related to Lactobacillus, Streptococcus and Streptococcus in colostrum. In addition, there are connections between different oligosaccharides in content. The study protocol was also registered in the ClinicalTrails.gov (ChiCTR2200064454) (Oct. 2022).

Psychological distress in adult women of reproductive age at different stages after breast cancer diagnosis: A qualitative study.

AIM: To explore the actual experience of psychological distress of adult women of reproductive age at different stages after breast cancer diagnosis. DESIGN: Qualitative. METHODS: Eighty-one patients with breast cancer-related distress thermometer scores >4 were selected using a purposive sampling method. Patients were divided into newly diagnosed and 1-, 3-, 6-, 9- and 12-month groups according to time since diagnosis and then interviewed. A phenomenological approach was adopted to analyse interview content, and different themes were extracted. RESULTS: Women exhibited different levels of psychological distress depending on the time since diagnosis, with newly diagnosed patients showing the highest distress. Within 1 year post-diagnosis, different events caused patients distress. Themes extracted at new diagnosis and 1-, 3-, 6-, 9- and 12 months post-diagnosis included sadness and disbelief, loss of control, optimistic but concerned, physical and mental exhaustion, difficulties returning to society and limited sexual intimacy, respectively; all groups expressed reproductive concerns. CONCLUSION: Clinical nurses should focus on different psychologically distressing events to provide targeted interventions at distinct phases. For women of childbearing age, clinical nurses should pay particular attention to patients' marriage and reproductive concerns. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: During the year after a breast cancer diagnosis, patients of childbearing age experience events that cause psychological distress that differ depending on time since diagnosis. Nurses should focus on core stressful events and perform specific nursing interventions. IMPACT: To provide holistic care, nurses should consider the psychological and emotional changes patients may undergo. For women of childbearing age, clinical nurses should pay particular attention to patients' marriage and fertility concerns, and be able to provide evidence-based professional guidance on reproductive preservation techniques. REPORTING METHOD: The study was reported using the consolidated criteria for reporting qualitative research guidelines. PATIENT OR PUBLIC CONTRIBUTION: Patients contributed to data collection through interviews.

Associations of body roundness index with cardiovascular and all-cause mortality: NHANES 2001-2018.

Body roundness index (BRI) was associated with cardiovascular diseases. But the relationship between BRI with cardiovascular disease (CVD) mortality and all-cause mortality remains largely unknown in hypertensive patients. This prospective cohort study included patients with hypertension who participated in the National Health and Nutrition Examination Survey (NHANES) from 2001 through 2018, and aimed to evaluate the association between BRI with CVD mortality and all-cause mortality. A total of 15570 patients were included. Over a median follow-up of 8.0 years (interquartile range, 4.3-12.6 years), 3445 individuals died, including 1166 CVD deaths. Weighted restricted cubic spline regression results showed a nonlinear association between BRI and CVD mortality and all-cause mortality (both P for nonlinear trend <0.001). The weighted multivariate Cox proportional hazards regression showed the hazard ratio (HRs) for CVD mortality were 0.93 (95% CI: 0.84-1.03, P = 0.160) in the low levels of BRI (≤5.9) and 1.11 (95% CI: 1.05-1.19, P < 0.001) in the high levels of BRI (>5.9). Similar associations were observed for all-cause mortality, the HRs were 0.91 (95% CI: 0.87-0.96, P < 0.001) in the low levels of BRI (≤6.3) and 1.09 (95% CI: 1.05-1.13, P < 0.001) in the high levels of BRI (>6.3). This cohort study supported that BRI was nonlinearly associated with CVD mortality and all-cause mortality among patients with hypertension. The thresholds of 5.9 and 6.3 for CVD mortality and all-cause mortality, respectively, may represent intervention targets for lowering the risk of premature death, but this needs to be confirmed in large clinical trials.

Relationships between Attachment Style, Emotional Self-Disclosure, and Quality of Life among Young Breast Cancer Survivors: A Cross-Sectional Study.

OBJECTIVES: This investigation aims to explore relationships between adult attachment, emotional self-disclosure, and quality of life (QoL). DATA SOURCES: The study sample completed the Chinese versions of the Experiences in Close Relationships Inventory, the Functional Assessment of Cancer Therapy-Breast Scale, and the Distress Disclosure Index between October 2021 and March 2022. The relationships between adult attachment, emotional self-disclosure, and QoL were investigated using a multiple mediation effects test and structural equation modeling. CONCLUSION: Attachment anxiety and avoidance were risk factors for young Chinese breast cancer survivors' emotional self-disclosure and QoL. Emotional self-disclosure mediates the association between attachment anxiety or avoidance and QoL. Assessing and easing attachment anxiety and avoidance may improve the emotional self-disclosure and QoL of young breast cancer survivors. IMPLICATIONS FOR NURSING PRACTICE: This study confirms that adult attachment plays an important role in young breast cancer patients' adaptation to the disease and that high adult anxiety and avoidance levels can significantly reduce emotional self-disclosure and QoL in young breast cancer survivors. Identifying attachment patterns can help caregivers better understand patients' responses, adaptation, and treatment adherence to cancer, thereby helping caregivers develop targeted and personalized cancer care practice programs or psychotherapy interventions to improve patients' physical and mental health outcomes.

TheMarker: a comprehensive database of therapeutic biomarkers.

Distinct from the traditional diagnostic/prognostic biomarker (adopted as the indicator of disease state/process), the therapeutic biomarker (ThMAR) has emerged to be very crucial in the clinical development and clinical practice of all therapies. There are five types of ThMAR that have been found to play indispensable roles in various stages of drug discovery, such as: Pharmacodynamic Biomarker essential for guaranteeing the pharmacological effects of a therapy, Safety Biomarker critical for assessing the extent or likelihood of therapy-induced toxicity, Monitoring Biomarker indispensable for guiding clinical management by serially measuring patients' status, Predictive Biomarker crucial for maximizing the clinical outcome of a therapy for specific individuals, and Surrogate Endpoint fundamental for accelerating the approval of a therapy. However, these data of ThMARs has not been comprehensively described by any of the existing databases. Herein, a database, named 'TheMarker', was therefore constructed to (a) systematically offer all five types of ThMAR used at different stages of drug development, (b) comprehensively describe ThMAR information for the largest number of drugs among available databases, (c) extensively cover the widest disease classes by not just focusing on anticancer therapies. These data in TheMarker are expected to have great implication and significant impact on drug discovery and clinical practice, and it is freely accessible without any login requirement at: https://idrblab.org/themarker.