Father support breastfeeding self-efficacy positively affects exclusive breastfeeding at 6 weeks postpartum and its influencing factors in Southeast China: a multi-centre, cross-sectional study.

BACKGROUND: The exclusive breastfeeding condition in China is not optimism now. Maternal breastfeeding self-efficacy stands as a pivotal factor influencing exclusive breastfeeding. Interestingly, studies have suggested that father support breastfeeding self-efficacy is a pivotal mediator in infant breastfeeding. Thus, the current research aimed to investigate the association between father support breastfeeding self-efficacy and exclusive breastfeeding at six weeks postpartum, and the influencing factors of father support breastfeeding self-efficacy. METHODS: This research was structured as a multi-centre cross-sectional study, involving 328 fathers, whose partners were six weeks postpartum, and recruited from two public hospitals in Southeast China. Self-designed demographic questionnaires, namely, Father Support Breastfeeding Self-Efficacy Scale-Short Form, Breastfeeding Knowledge Questionnaire, Positive Affect Scale and the 14-item Fatigue Scale, were applied. Descriptive statistics, Chi-square test, logistic regression univariate analysis and multiple linear regression were used to analyse data. RESULTS: Results indicate a significant difference between the infant feeding methods at six weeks postpartum and fathers with different levels of support breastfeeding self-efficacy (p < 0.05). Particularly, father support breastfeeding self-efficacy positively affected exclusive breastfeeding at six weeks postpartum after adjusting all the demographic characteristics of fathers (OR: 2.407; 95% CI: 1.017-4.121). Moreover, results show that the significant influencing factors of father support breastfeeding self-efficacy include breastfeeding knowledge, fatigue, positive affect, successfully experienced helping mothers to breastfeed, spousal relationships and companionship time. CONCLUSIONS: High-level father support breastfeeding self-efficacy effectively increased exclusive breastfeeding rate at six weeks postpartum. To enhance the exclusive breastfeeding rate, nurses or midwives can endeavour to design educational programmes or take supportive interventions customised for fathers, such as enhancing their breastfeeding knowledge education, reducing fatigue and mobilising positive emotions, thereby bolstering paternal self-efficacy in breastfeeding.

Why does distilled liquor (Baijiu) have a yellowish color: A comprehensive analysis.

Elucidating the mechanisms underlying Baijiu production is a shared aspiration among academic groups specializing in the field of Baijiu research. This study comprehensively examined the mechanisms underlying the yellowish coloration of Baijiu through a synergistic application of chromatographic, spectroscopic, and physical methodologies. Aging of Baijiu in earthenware pots involves the infiltration of mineral ions such as iron, aluminum, and calcium; however, these ions are detected at extremely low concentrations and are therefore not linked to the development of Baijiu's yellowish color. Instead, the yellowish coloration is attributed to the diverse colorants generated during the high-temperature fermentation of small-molecule sugars derived from the saccharification of grain materials. Although these colorants exist in minimal quantities and exhibit spectral absorption peaks ranging from 300 to 450 nm, their overlapping spectra collectively contribute to the light-absorbing properties of Baijiu across a broad wavelength range, ultimately accounting for its characteristic yellowish color.

Liquid-liquid phase separation-related genes associated with prognosis, tumor microenvironment characteristics, and tumor cell features in bladder cancer.

OBJECTIVE: This study aimed to explore the Liquid-liquid phase separation (LLPS)-related genes associated with the prognosis of bladder cancer (BCa) and assess the potential application of LLPS-related prognostic signature for predicting prognosis in BCa patients. METHODS: Clinical information and transcriptome data of BCa patients were extracted from the Cancer Genome Atlas-BLCA (TCGA-BLCA) database and the GSE13507 database. Furthermore, 108 BCa patients who received treatment at our institution were subjected to a retrospective analysis. The least absolute shrinkage and selection operator (LASSO) analysis was performed to develop an LLPS-related prognostic signature for BCa. The CCK8, wound healing and Transwell assays were performed. RESULTS: Based on 62 differentially expressed LLPS-related genes (DELRGs), three DELRGs were screened by LASSO analysis including kallikrein-related peptidase 5 (KLK5), monoacylglycerol O-acyltransferase 2 (MOGAT2) and S100 calcium-binding protein A7 (S100A7). Based on three DELRGs, a novel LLPS-related prognostic signature was constructed for individualized prognosis assessment. Kaplan-Meier curve analyses showed that LLPS-related prognostic signature was significantly correlated with overall survival (OS) of BCa. ROC analyses demonstrated the LLPS-related prognostic signature performed well in predicting the prognosis of BCa patients in the training group (the area under the curve (AUC) = 0.733), which was externally verified in the validation cohort 1 (AUC = 0.794) and validation cohort 2 (AUC = 0.766). Further experiments demonstrated that inhibiting KLK5 could affect the proliferation, migration, and invasion of BCa cells. CONCLUSIONS: In this study, a novel LLPS-related prognostic signature was successfully developed and validated, demonstrating strong performance in predicting the prognosis of BCa patients.

Molten Salt Modulation of Potassium-Nitrogen-Carbon for the Breaking Kinetics Bottleneck of Photocatalytic Overall Water Splitting and Environmental Impact Reduction.

Sluggish interfacial water dissociation and the O2 evolution reaction (OER) kinetics are the main obstacles that limit the photocatalytic overall water-splitting performance. A molten salt modulation of potassium-nitrogen-carbon is herein demonstrated as the formation of highly crystalline potassium-doped poly(triazine imide) (KPTI). The in situ X-ray diffraction patterns and theoretical calculation show that the KCl melt can significantly reduce the free energy for the polycondensation of triazine building blocks owing to the formation of a kinetically stable KPTI. Benefiting from the presence of potassium-carbon-nitrogen moiety, the catalyst not only weakens the excitonic confinement to improve the separation efficiency of photogenerated charge carriers but also enhances the stability of carbon sites by suppressing the undesired C═O formation. Moreover, KPTI accelerates water dissociation by forming interfacial K·H2O clusters with an ordered structure, which supplies sufficient protons for the H2 evolution reaction and lowers the energy barrier to enhance the kinetics of OER. Therefore, a stable photocatalytic overall water-splitting performance can be achieved over KPTI with a stoichiometric generation of products (H2 and O2). Life cycle assessment shows that a carbon-neutral scenario can be achieved on KPTI production in the near term with an increase in green power in the electricity grid.

Efficacy and safety of GLP-1 analog ecnoglutide in adults with type 2 diabetes: a randomized, double-blind, placebo-controlled phase 2 trial.

Glucagon-like peptide-1 (GLP-1) analogs are important therapeutics for type 2 diabetes and obesity. Ecnoglutide (XW003) is a novel, long-acting GLP-1 analog. We conducted a Phase 2, randomized, double-blind, placebo-controlled study enrolling 145 adults with T2DM. Participants were randomized to 0.4, 0.8, or 1.2 mg ecnoglutide or placebo as once-weekly injections for 20 weeks. The primary objective was to evaluate the efficacy of ecnoglutide, as measured by HbA1c change from baseline at Week 20. Secondary endpoints included body weight, glucose and lipid parameters, as well as safety. We show that, at end of treatment, the 0.4, 0.8, and 1.2 mg groups had statistically significant HbA1c reductions from baseline of -1.81%, -1.90%, and -2.39%, respectively, compared to -0.55% for placebo (P < 0.0001). At end of treatment, 71.9% of the 1.2 mg group had HbA1c ≤ 6.5% versus 9.1% on placebo, and 33.3% had body weight reductions ≥5% versus 3.0% for placebo. Ecnoglutide was generally safe and well tolerated. China Drug Trials Registry CTR20211014.

Nondissociative Activated Dihydrogen Binding on CeO2 Revealed by High-Pressure Operando Solid-State NMR Spectroscopy.

Dihydrogen complexes, which retain the H-H bond, have been extensively studied in molecular science and found to be prevalent in homogeneous and enzymatic catalysis. However, their counterparts in heterogeneous catalysis, specifically nondissociative chemisorbed dihydrogen binding on the catalyst surface, are rarely reported experimentally. This scarcity is due to the complexity of typical material surfaces and the lack of effective characterization techniques to prove and distinguish various dihydrogen binding modes. Herein, using high-pressure operando solid-state NMR technology, we report the first unambiguous experimental observation of activated dihydrogen binding on a reduced ceria catalyst through interactions with surface oxygen vacancies. By employing versatile NMR structural and dynamical analysis methods, we establish a proportional relationship between the degree of ceria surface reduction and dihydrogen binding, as evidenced by NMR observations of H-D through-bond coupling (JHD), T1 relaxation, and proton isotropic chemical shifts. In situ NMR analysis further reveals the participation of bound dihydrogen species in a room-temperature ethylene hydrogenation reaction. The remarkable similarities between surface-activated dihydrogen in heterogeneous catalysis and dihydrogen model molecular complexes can provide valuable insights into the hydrogenation mechanism for many other solid catalysts, potentially enhancing hydrogen utilization.

S. aureus Eap is a polyvalent inhibitor of neutrophil serine proteases.

Staphylococcus aureus expresses three high-affinity neutrophil serine protease (NSP) inhibitors known as the extracellular adherence protein domain (EAPs) proteins. Whereas EapH1 and EapH2 are comprised of a single EAP domain, the modular extracellular adherence protein (Eap) from S. aureus strain Mu50 consists of four EAP domains. We recently reported that EapH2 can simultaneously bind and inhibit cathepsin-G (CG) and neutrophil elastase (NE), which are the two most abundant NSPs. This unusual property of EapH2 arises from independent CG and NE-binding sites that lie on opposing faces of its EAP domain. Here we used X-ray crystallography and enzyme assays to show that all four individual domains of Eap (i.e. Eap1, Eap2, Eap3, and Eap4) exhibit an EapH2-like ability to form ternary complexes with CG and NE that inhibit both enzymes simultaneously. We found that Eap1, Eap2, and Eap3 have similar functional profiles insofar as NSP inhibition is concerned but that Eap4 displays an unexpected ability to inhibit two NE enzymes simultaneously. Using X-ray crystallography, we determined that this second NE-binding site in Eap4 arises through the same region of its EAP domain that also comprises its CG-binding site. Interestingly, small angle X-ray scattering data showed that stable tail-to-tail dimers of the NE/Eap4/NE ternary complex exist in solution. This arrangement is compatible with NSP-binding at all available sites in a two-domain fragment of Eap. Together, our work implies that Eap is a polyvalent inhibitor of NSPs. It also raises the possibility that higher-order structures of NSP-bound Eap may have unique functional properties.

Boost Infiltration and Activity of T Cells via Inhibiting Ecto-5'-nucleotidase (CD73) Immune Checkpoint to Enhance Glioblastoma Immunotherapy.

The currently available immune checkpoint therapy shows a disappointing therapeutic efficacy for glioblastoma multiforme (GBM), and it is of great importance to discover better immune checkpoints and develop innovative targeting strategies. The discovered metabolic immune checkpoint ecto-5-nucleotidase (CD73) in a tumor contributes to its immune evasion due to the dysregulation of extracellular adenosine (ADO), which significantly inhibits the function of antitumor T cells and increases the activity of immunosuppressive cells. Herein, we drastically inhibit the expression of CD73 to reduce the production of ADO by using versatile Au@Cu2-xSe nanoparticles (ACS NPs). ACS NPs can decrease the expression of CD73 by alleviating the tumor hypoxia through their Fenton-like reaction to weaken the ADO-driven immunosuppression for enhancing antitumor T cell infiltration and activity of GBM. The copper ions (Cu2+) released from ACS NPs can chelate with disulfide, leading to the formation of cytotoxic bis(N,N-diethyldithiocarbamate)-copper complex (CuET), which can be combined with radiotherapy to recruit more antitumor T cells to infiltrate into the tumor site. Based on the inhibition of CD73 to promote the infiltration and activity of antitumor T cells, a cascade of enhancing GBM immunotherapy effects can be achieved. The significant increase in CD8+ T and CD4+ T cells within the tumor and the memory T cells in the spleen effectively reduces tumor size by 92%, which demonstrates the excellent efficacy of immunotherapy achieved by a combination of metabolic immune checkpoint CD73 inhibition with chemoradiotherapy. This work demonstrates that modulation of CD73-mediated tumor immunosuppression is an important strategy of improving the outcome of GBM immunotherapy.

Intuitive eating was associated with anxiety, depression, pregnancy weight and blood glucose in women with gestational diabetes mellitus: a prospective longitudinal study.

Background: Outside of pregnancy, intuitive eating (IE) is associated with lower body weight, blood glucose, and higher positive mood. However, little was known about the relationship between IE and anxiety-depression in the GDM population. Thus, this study aimed to investigate the association of IE with anxiety and depression, pregnancy weight and pregnancy blood glucose in the first and second GDM visit. Methods: Data from 310 pregnant women with GDM from the Fujian Maternal and Child Health Hospital Trial (Approval Number: 2020Y9133) were analyzed. IE was assessed using the Intuitive Eating Scale-2 subscales of Eating for Physiological Reasons rather than Emotional Reasons (EPR), Relying on Hunger and Satiety Cues (RHSC) and Body-Food Choice Consistency (B-FCC). Observations included weight, body mass index (BMI), fasting plasma glucose (FPG) and 2-h postprandial blood glucose; the Hospital Anxiety and Depression Scale (HADS) was used to assess the level of anxiety and depression in pregnant women with GDM. Linear regression analysis was used to assess the correlation between IE and anxiety, depression, pregnancy blood glucose and weight. Results: The cross-sectional analysis showed that the EPR eating behavior was negatively correlated with anxiety and depression, and the B-FCC eating behavior was negatively correlated with depression at both the first and second GDM visit; in addition, the B-FCC eating behavior was associated with lower BMI in the third trimester (all p < 0.05). In longitudinal analyses, the EPR eating behavior in the first visit for GDM predicted lower levels of anxiety and depression in the second GDM visit, whereas the RHSC eating behavior in the first visit for GDM was associated with lower FPG in the second GDM visit (all p < 0.01). Conclusion: These results suggest that practicing intuitive eating may be beneficial and that higher intuitive eating adherence can lead to lower levels of anxiety and depression and more ideal gestational weight and blood glucose values.

Impact of dietary inflammatory index on gestational diabetes mellitus in normal and overweight women: a systematic review and meta-analysis of observational studies.

BACKGROUND AND OBJECTIVES: To systematically investigate the association between the dietary inflammatory index (DII) and gestational diabetes mellitus (GDM), with a focus on the role of BMI in this relationship. METHODS AND STUDY DESIGN: A comprehensive search was conducted in PubMed, Embase, Web of Science, The Cochrane Library, Medline, CINAHL Complete, Chinese Periodical Full-text Database, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, and China Wanfang Database for rele-vant observational studies published up to August 2023. The quality of the included studies was assessed using the Newcastle-Ottawa Scale. The pooled effect size was calculated using a random-effects model. Sub-group and meta-regression analyses were performed to explore potential sources of heterogeneity. RESULTS: The study included 54,058 participants from 10 studies. Pregnant women with a higher DII, indicating a pro-inflammatory diet, had a significantly increased risk of GDM compared to those with a lower DII, indicating an anti-inflammatory diet (pooled OR: 1.17, 95% CI: 1.01-1.36; I²=70%, p <0.001). Subgroup analyses revealed a stronger association in normal weight stratification (OR: 1.25, 95%CI: 1.04-1.51), case-control studies (OR: 1.45, 95%CI: 1.03-2.05), Asia (OR: 1.26, 95%CI: 1.10-1.43), Europe (OR: 1.27, 95%CI: 1.09-1.48), 3-day dietary record as a dietary assessment tool (OR: 1.30, 95%CI: 1.16-1.46), physical activity adjustment (OR: 1.28, 95%CI: 1.13-1.46), and energy intake adjustment (OR: 1.33, 95%CI: 1.19-1.48). Meta-regression analysis confirmed that geographical region significantly influenced heterogeneity between studies (p <0.05). CONCLUSIONS: An elevated DII is independently linked to a higher risk of GDM, especially in women of normal weight.

Triggering Receptor Expressed on Myeloid Cells 2 Alleviated Sevoflurane-Induced Developmental Neurotoxicity via Microglial Pruning of Dendritic Spines in the CA1 Region of the Hippocampus.

Sevoflurane induces developmental neurotoxicity in mice; however, the underlying mechanisms remain unclear. Triggering receptor expressed on myeloid cells 2 (TREM2) is essential for microglia-mediated synaptic refinement during the early stages of brain development. We explored the effects of TREM2 on dendritic spine pruning during sevoflurane-induced developmental neurotoxicity in mice. Mice were anaesthetized with sevoflurane on postnatal days 6, 8, and 10. Behavioral performance was assessed using the open field test and Morris water maze test. Genetic knockdown of TREM2 and overexpression of TREM2 by stereotaxic injection were used for mechanistic experiments. Western blotting, immunofluorescence, electron microscopy, three-dimensional reconstruction, Golgi staining, and whole-cell patch-clamp recordings were performed. Sevoflurane exposures upregulated the protein expression of TREM2, increased microglia-mediated pruning of dendritic spines, and reduced synaptic multiplicity and excitability of CA1 neurons. TREM2 genetic knockdown significantly decreased dendritic spine pruning, and partially aggravated neuronal morphological abnormalities and cognitive impairments in sevoflurane-treated mice. In contrast, TREM2 overexpression enhanced microglia-mediated pruning of dendritic spines and rescued neuronal morphological abnormalities and cognitive dysfunction. TREM2 exerts a protective role against neurocognitive impairments in mice after neonatal exposures to sevoflurane by enhancing microglia-mediated pruning of dendritic spines in CA1 neurons. This provides a potential therapeutic target in the prevention of sevoflurane-induced developmental neurotoxicity.

Study on the Diffusion Law of Heavy Gas Leakage in Complex Scenarios Based on Scaled-Down Experiments.

In order to study the effects of temperature, wind speed, and leakage volume on the diffusion of heavy gas leakage, this paper establishes a scaling model for the experimental study of gas leakage and diffusion by using the similarity theory with a certain factory as the target. And carbon dioxide gas is selected to replace the toxic and harmful heavy gas to carry out experiments under different temperatures (0-40 °C), wind speeds (0-2 m/s), and leakage velocities (2.5-12.5 L/min), respectively. The results showed that the diffusion rate of heavy gas expanded with increasing temperature under the conditions of wind speed of 0.25 m/s and leakage velocity of 1.5 L/min. When the temperature was increased from 0 to 40 °C, the concentration increase at each location was 125-290% at 600 s. Under the condition of temperature of 20 °C and leakage velocity of 5 L/min, the concentration at each location increased linearly with diffusion time when there was wind, while the linear relationship was not obvious when there was no wind. The effect on the concentration was larger when the wind speed was less than 1 m/s and smaller when the wind speed was greater than 1 m/s. At 20 °C and a wind speed of 0.5 m/s, the concentration of carbon dioxide at each location was increasing as the leakage increased. As the leakage velocity increases from 2.5 to 12.5 L/min, the carbon dioxide concentration at 600 s spreads 2-14 times. The research in this paper provides some decision support for the rescue work, which is important for improving the emergency rescue capability of the leakage accident.

Effect of static lung expansion on pulmonary function following cardiopulmonary bypass in children.

Objective: To observe the effect of the lung-protective ventilation strategy, static lung expansion, during cardiopulmonary bypass (CPB) on pulmonary function and tracheal intubation time following cardiac surgery in children. Methods: A total of 48 child patients (aged 1-3) with ventricular septal defect (VSD) were enrolled, and all underwent CPB cardiac surgery for the first time. The patients were divided into two groups using the random number table method: the experimental group (Group A, n = 30) and the control group (Group B, n = 18). After terminating the mechanical ventilation during CPB, the adjustable pressure limiting valve of the anesthesia machine was adjusted in the experimental group to maintain the pressure of the breathing circuit at 5 cmH2O, such that both lungs remained in a static expansion state. In the control group, routine mechanical ventilation was terminated as usual. Results: When static lung expansion with a continuous positive airway pressure of 5 cmH2O was employed in the VSD children during CPB, compared with termination of mechanical ventilation, the partial pressure of oxygen in the arterial blood increased, while the respiratory index decreased and the oxygenation index increased following the surgery. Conclusion: In child patients undergoing VSD reparation under CPB, lung injury occurs following the procedure, and the pulmonary oxygenation function and pulmonary oxygen diffusion function decrease. When static lung expansion of 5 cmH2O is performed during CPB, the improvement in lung function is better than that of apnea without lung expansion pressure.

circUQCRC2 promotes asthma progression in children by activating the VEGFA/NF-κB pathway by targeting miR-381-3p.

This study targeted to explore circUQCRC2's role and mechanism in childhood asthma. A mouse model of ovalbumin-induced asthma was established to evaluate the effects of circUQCRC2 on childhood asthma in terms of oxidative stress, inflammation, and collagen deposition. The effects of circUQCRC2 on platelet-derived growth factor-BB (PDGF-BB)-induced smooth muscle cells (SMCs) were evaluated, the downstream mRNA of miRNA and its associated pathways were predicted and validated, and their effects on asthmatic mice were evaluated. circUQCRC2 levels were upregulated in bronchoalveolar lavage fluid of asthmatic mice and PDGF-BB-treated SMCs. Depleting circUQCRC2 alleviated tissue damage in asthmatic mice, improved inflammatory levels and oxidative stress in asthmatic mice and PDGF-BB-treated SMC, inhibited malignant proliferation and migration of SMCs, and improved airway remodeling. Mechanistically, circUQCRC2 regulated VEGFA expression through miR-381-3p and activated the NF-κB cascade. circUQCRC2 knockdown inactivated the NF-κB cascade by modulating the miR-381-3p/VEGFA axis. Promoting circUQCRC2 stimulates asthma development by activating the miR-381-3p/VEGFA/NF-κB cascade. Therefore, knocking down circUQCRC2 or overexpressing miR-381-3p offers a new approach to treating childhood asthma.

[Clinical effects of transesophageal echocardiography in different surgical methods for nephrectomy combined with Mayo â ¢-â £ vena tumor thrombectomy].

OBJECTIVE: To analyze the clinical effects of intraoperative transesophageal echocardiography (TEE) in different surgical methods for nephrectomy combined with Mayo Ⅲ-Ⅳ inferior vena cave (IVC) tumor thrombectomy. METHODS: In the study, 28 patients who did surgery of nephrectomy and Mayo Ⅲ-Ⅳ IVC thrombectomys in Peking University Third Hospital from 2022 January to 2024 February were included. Of the 28 patients, 16 patients did robotic surgery, 2 patients did laparoscopic surgery, and 10 patients did open surgery. All patients' clinical data were collected. RESULTS: Intra-operative TEE was used in 9 robotic surgeries, of which 7 cases showed image changes compared with preoperative image results. Intraoperative TEE indicated that tumor thrombus entered the right atrium in 2 cases, showed that tumor thrombus grade rose from Mayo Ⅲ to Mayo Ⅳ in 2 cases, and indicated that tumor thrombus adhered to IVC wall in 3 cases. All of these surgical plans were timely adjusted. Intra-operative TEE was used in 6 cases of open surgery, and 4 cases of them showed Mayo grade changes compared with preoperative image results. Intraoperative TEE indicated that tumor thrombus adhered to the IVC wall in 3 cases, and tumor thrombus adhered to the IVC wall with thrombus in one case. The surgical plans were adjusted, and the tumor thrombus was left or segmentally removed. Laparoscopic surgery did not use intraoperative TEE. The effects of intraoperative TEE included: the combination of exploration and TEE monitoring was used in open surgery, and tumor thrombus removal process was fully monitored by intraoperative TEE in the robotic surgery. Intraoperative TEE real-time monitored circulatory status and cardiac function changes. CONCLUSION: In different surgical methods for nephrectomy combined with Mayo Ⅲ-Ⅳ tumor thrombectomy, intraoperative TEE can re-determine the tumor thrombus grade and degree of tumor thrombus adhered to IVC, track the tumor thrombus removal process in real-time, and monitor circulatory status and cardiac function changes. Intraoperative TEE plays an important role in different surgical methods, but its clinical application is still insufficient. Intraoperative TEE is recommended to such type of surgeries.

Machine learning-based autophagy-related prognostic signature for personalized risk stratification and therapeutic approaches in bladder cancer.

OBJECTIVE: Bladder cancer (BCa) is a highly lethal urological malignancy characterized by its notable histological heterogeneity. Autophagy has swiftly emerged as a diagnostic and prognostic biomarker in diverse cancer types. Nonetheless, the currently accessible autophagy-related signature specific to BCa remains limited. METHODS: A refined autophagy-related signature was developed through a 10-fold cross-validation framework, incorporating 101 combinations of machine learning algorithms. The performance of this signature in predicting prognosis and response to immunotherapy was thoroughly evaluated, along with an exploration of potential drug targets and compounds. In vitro and in vivo experiments were conducted to verify the regulatory mechanism of hub gene. RESULTS: The autophagy-related prognostic signature (ARPS) has exhibited superior performance in predicting the prognosis of BCa compared to the majority of clinical features and other developed markers. Higher ARPS is associated with poorer prognosis and reduced sensitivity to immunotherapy. Four potential targets and five therapeutic agents were screened for patients in the high-ARPS group. In vitro and vivo experiments have confirmed that FKBP9 promotes the proliferation, invasion, and metastasis of BCa. CONCLUSIONS: Overall, our study developed a valuable tool to optimize risk stratification and decision-making for BCa patients.

A case study of Duchenne muscular dystrophy caused by Alu element insertion in DMD gene and analysis of its gray-hair symptoms.

Duchenne muscular dystrophy (DMD) is a severe X-linked recessive genetic disorder caused by mutations in the DMD gene, which leads to a deficiency of the dystrophin protein. The main mutation types of this gene include exon deletions and duplications, point mutations, and insertions. These mutations disrupt the normal expression of dystrophin, ultimately leading to the disease. In this study, we reported a case of DMD caused by an insertion mutation in exon 59 (E59) of the DMD gene. The affected child exhibited significant abnormalities in related biochemical markers, early symptoms of DMD, and multiple gray hair. His mother and sister were carriers with slightly abnormal biochemical markers. The mother had mild clinical symptoms, while the sister had no clinical symptoms. Other family members were genetically and physically normal. Sequencing and sequence alignment revealed that the inserted fragment was an Alu element from the AluYa5 subfamily. This insertion produced two stop codons and a polyadenylate (polyA) tail. To understand the impact of this insertion on the DMD gene and its association with clinical symptoms, exonic splicing enhancer (ESE) prediction indicated that the insertion did not affect the splicing of E59. Therefore, we speculated that the insertion sequence would be present in the mRNA sequence of the DMD gene. The two stop codons and polyA tail likely terminate translation, preventing the production of functional dystrophin protein, which may be the mechanism leading to DMD. In addition to typical DMD symptoms, the child also exhibited premature graying of hair. This study reports, for the first time, a case of DMD caused by the insertion of an Alu element into the coding region of the DMD gene. This finding provides clues for studying gene mutations induced by Alu sequence insertion and expands the understanding of DMD gene mutations.

Environmental explanation of prostate cancer progression based on the comprehensive analysis of polychlorinated biphenyls.

OBJECTIVE: Polychlorinated biphenyls (PCBs) have caused great environmental concerns. The study aims to investigate underlying molecular mechanisms between PCBs exposure and prostate cancer (PCa). METHODS: To investigate the association between PCBs exposure and prostate cancer by using CTD, TCGA, and GEO datasets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to explore pathways associated with PCBs-related genes (PRGs). Using Lasso regression analysis, a novel PCBs-related prognostic model was developed. Both internal and external validations were conducted to assess the model's validity. Molecular docking was utilized to assess the binding capacity of PCBs to crucial genes. At last, preliminary experimental validations were conducted to confirm the biological roles of Aroclor 1254 in PCa cells. RESULTS: The GO enrichment analysis of PRGs revealed that the biological processes were most enriched in the regulation of transcription from the RNA polymerase II promoter and signal transduction. The KEGG enrichment analysis showed that of the pathways in cancer is the most significantly enriched. Next, a PCBs-related model was constructed. In the training, test, GSE70770, and GSE116918 cohorts, the biochemical recurrences free survival of the patients with high-risk scores was considerably lower. The AUCs at 5 years were 0.691, 0.718, 0.714, and 0.672 in the four cohorts, demonstrating the modest predictive ability. A nomogram that incorporated clinical characteristics was constructed. The results of the anti-cancer drug sensitivity analysis show chemotherapy might be more beneficial for patients at low risk. The molecular docking analysis demonstrated PCBs' ability to bind to crucial genes. PCa cells exposed to Aroclor 1254 at a concentration of 1 µM showed increased proliferation and invasion capabilities. CONCLUSIONS: This study provides new insights into the function of PCBs in PCa and accentuates the need for deeper exploration into the mechanistic links between PCBs exposure and PCa progression.

Magnetic resonance imaging-based radiomics nomogram for the evaluation of therapeutic responses to neoadjuvant chemohormonal therapy in high-risk non-metastatic prostate cancer.

PURPOSE: The aim of this study was to assess the potential application of a radiomics features-based nomogram for predicting therapeutic responses to neoadjuvant chemohormonal therapy (NCHT) in patients with high-risk non-metastatic prostate cancer (PCa). METHODS: Clinicopathologic information was retrospectively collected from 162 patients with high-risk non-metastatic PCa receiving NCHT and radical prostatectomy at our center. The postoperative pathological findings were used as the gold standard for evaluating the efficacy of NCHT. The least absolute shrinkage and selection operator (LASSO) was conducted to develop radiomics signature. Multivariate logistic regression analyses were conducted to identify the predictors of a positive pathological response to NCHT, and a nomogram was constructed based on these predictors. RESULTS: Sixty-three patients (38.89%) experienced positive pathological response to NCHT. Receiver operating characteristic analyses showed that the area under the curve (AUC) of periprostatic fat (PPF) radiomics signature was 0.835 (95% CI, 0.754-0.898), while the AUC of intratumoral radiomics signature was 0.822 (95% CI, 0.739-0.888). Multivariate logistic regression analysis revealed that PSA level, PPF radiomics signature and intratumoral radiomics signature were independent predictors of positive pathological response. A nomogram based on these three predictors was constructed. The AUC was 0.908 (95% CI, 0.839-0.954). The Hosmer-Lemeshow goodness-of-fit test showed that the nomogram was well calibrated. Decision curve analysis revealed the favorable clinical practicability of the nomogram. The nomogram was successfully validated in the validation cohort. Kaplan-Meier analyses showed that nomogram and positive pathological response were significantly related with survival of PCa. CONCLUSION: The radiomics-clinical nomogram based on mpMRI radiomics features exhibited superior predictive ability for positive pathological response to NCHT in high-risk non-metastatic PCa.