The effects of antimicrobial peptides buCaTHL4B and Im-4 on infectious root canal biofilms.

Purpose: The primary cause of pulp and periapical diseases is the invasion of bacteria into the root canal, which results from the continuous destruction of dental hard tissues. Effective management of infections during root canal therapy necessitates effectively irrigation. This study aims to investigate the effects of two antimicrobial peptides (AMPs), buCaTHL4B and Im-4, on root canal biofilms in vitro. Methods: Two-species biofilms (Enterococcus faecalis and Fusobacterium nucleatum) were selected and anaerobically cultivated. The following treatments were applied: 10 µg/mL buCaTHL4B, 10 µg/mL Im-4, 5 µg/mL buCaTHL4B, 5 µg/mL Im-4, 1 µg/mL buCaTHL4B, 1 µg/mL Im-4, 1% NaOCl, and sterile water. Each group was treated for 3 min. Subsequently, the two strains were co-cultured with 10 µg/mL buCaTHL4B, 10 µg/mL Im-4, 1% NaOCl, and sterile water for 24, 48, and 72 h. The biofilms were examined using confocal laser scanning microscopy (CLSM) with fluorescent staining, and the percentages of dead bacteria were calculated. Quantitative real-time PCR (qRT-PCR) was employed to assess the variations in bacterial proportions during biofilm formation. Results: Compared to 1% NaOCl, 10 µg/mL buCaTHL4B or Im-4 exhibited significantly greater bactericidal effects on the two-species biofilms (p < 0.05), leading to their selection for subsequent experiments. Over a 48-hour period, 10 µg/mL Im-4 demonstrated a stronger antibiofilm effect than buCaTHL4B (p < 0.05). Following a 24-hour biofilm formation period, the proportion of F. nucleatum decreased while the proportion of E. faecalis increased in the sterile water group. In the buCaTHL4B and 1% NaOCl groups, the proportion of F. nucleatum was lower than that of E. faecalis (p < 0.05), whereas in the Im-4 group, the proportion of F. nucleatum was higher than that of E. faecalis (p < 0.05). The proportions of bacteria in the two AMPs groups gradually stabilized after 24 h of treatment. Conclusion: buCaTHL4B and Im-4 exhibited remarkable antibacterial and anti-biofilm capabilities against pathogenic root canal biofilms in vitro, indicating their potential as promising additives to optimize the effectiveness of root canal treatment as alternative irrigants.

The potential therapeutic effect of human umbilical cord mesenchymal stem cell-derived exosomes in bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is a chronic lung disease of preterm infants, with its incidence rising due to improved survival rates of these infants. BPD results from a combination of prenatal and postnatal factors, such as mechanical ventilation, oxygen toxicity, and infections, all of which significantly impact the prognosis and growth of affected infants. Current treatment options for BPD are largely supportive and do not address the underlying pathology. Exosomes are cell-derived bilayer-enclosed membrane structures enclosing proteins, lipids, RNAs, growth factors, cytokines and metabolites. They have become recognized as crucial regulators of intercellular communication in various physiological and pathological processes. Previous studies have revealed the therapeutic potential of human umbilical cord mesenchymal stem cells-derived exosomes (HUCMSCs-Exos) in promoting tissue repair and regeneration. Therefore, HUCMSCs-Exos maybe a promising and effective therapeutic modality for BPD. In this review, we firstly provide a comprehensive overview of BPD, including its etiology and the mechanisms of lung injury. Then we detail the isolation, characterization, and contents of HUCMSCs-Exos, and discuss their potential mechanisms of HUCMSCs-Exos in BPD treatment. Additionally, we summarize current clinical trials and discuss the challenges in translating these findings from bench to bedside. This review aims to lay the groundwork for future clinical applications of HUCMSCs-Exos in treating BPD.

Bilateral superselective adrenal artery embolization for bilateral primary aldosteronism: a novel approach in an efficacy and safety proof-of-principle trial.

Superselective adrenal artery embolization (SAAE) offers a novel approach for treating primary aldosteronism (PA). In this study, we aimed to assess the efficacy and safety of SAAE for the treatment of PA based on the lateralization results obtained from adrenal vein sampling (AVS).In this prospective study, we enrolled 40 patients with PA who underwent SAAE. The patients were categorized into two groups, unilateral PA and bilateral PA, based on AVS results. Clinical parameters and biochemical markers were assessed at 3 and 12 months postoperatively. The primary outcomes were changes in blood pressure and defined daily dose (DDD) of antihypertensive medications compared to baseline. Thirty-eight patients achieved technical success, with favorable clinical and biochemical efficacy rates. At three months postoperatively, the clinical efficacy rates were 79.2% and 78.6% for the UPA and BPA groups, respectively. At 12 months, the rates were 83.3% and 71.4%, respectively. Both groups exhibited a significant decrease in average blood pressure at 3 and 12 months compared with baseline (P < 0.001), and there was also a notable reduction in DDD (P < 0.05). At three months, the biochemical efficacy rates were 61.9% and 58.3% in the UPA and BPA groups, respectively. Due to loss to follow-up, biochemical indicators were not assessed at 12 months postoperatively. No severe adverse reactions occurred during or after SAAE. Patients with both UPA and BPA can benefit from SAAE. The superiority of bilateral adrenal artery embolization in the treatment of BPA over unilateral adrenal artery embolization requires further investigation.

Case report: A case of effective treatment of primary myelofibrosis with nodular panniculitis using ruxolitinib combined with corticosteroids.

We report the case of a 54-year-old healthy Han Chinese male presenting with fever, pallor, erythematous subcutaneous nodules on the limbs, and significant anemia as indicated by routine blood tests, with no response to antimicrobial therapy. Initial skin biopsy was inconclusive. The erythematous subcutaneous nodules on the limbs rapidly progressed to widespread subcutaneous nodules across the body, with worsening anemia. Bone marrow biopsy revealed multifocal fibroblastic proliferation with focal fibrosis, classified as MF-2, and positive for the JAK2V617F mutation alongside SRSF2 positivity. Whole-body PET-CT scans did not reveal any lymph nodes or suspect lesions with high SUV uptake. A subsequent skin biopsy identified the condition as nodular panniculitis (NP), leading to a final diagnosis of primary myelofibrosis(PMF)with NP. The patient initially received treatment with oral ruxolitinib and prednisone acetate, resulting in normalization of body temperature, resolution of erythematous nodules, and normalization of blood parameters.

Bone metastasis prediction in non-small-cell lung cancer: primary CT-based radiomics signature and clinical feature.

BACKGROUND: Radiomics provided opportunities to quantify the tumor phenotype non-invasively. This study extracted contrast-enhanced computed tomography (CECT) radiomic signatures and evaluated clinical features of bone metastasis in non-small-cell lung cancer (NSCLC). With the combination of the revealed radiomics and clinical features, the predictive modeling on bone metastasis in NSCLC was established. METHODS: A total of 318 patients with NSCLC at the Tianjin Medical University Cancer Institute & Hospital was enrolled between January 2009 and December 2019, which included a feature-learning cohort (n = 223) and a validation cohort (n = 95). We trained a radiomics model in 318 CECT images from feature-learning cohort to extract the radiomics features of bone metastasis in NSCLC. The Kruskal-Wallis and the least absolute shrinkage and selection operator regression (LASSO) were used to select bone metastasis-related features and construct the CT radiomics score (Rad-score). Multivariate logistic regression was performed with the combination of the Rad-score and clinical data. A predictive nomogram was subsequently developed. RESULTS: Radiomics models using CECT scans were significant on bone metastasis prediction in NSCLC. Model performance was enhanced with each information into the model. The radiomics nomogram achieved an AUC of 0.745 (95% confidence interval [CI]: 0.68,0.80) on predicting bone metastasis in the training set and an AUC of 0.808(95% confidence interval [CI]: 0.71,0.88) in the validation set. CONCLUSION: The revealed invisible image features were of significance on guiding bone metastasis prediction in NSCLC. Based on the combination of the image features and clinical characteristics, the predictive nomogram was established. Such nomogram can be used for the auxiliary screening of bone metastasis in NSCLC.

Safety and efficacy of bilateral superselective adrenal arterial embolization for treatment of idiopathic hyperaldosteronism: a prospective single-center study.

OBJECTIVE: This study aimed to assess the efficacy and safety of bilateral superselective adrenal arterial embolization (SAAE) in patients with bilateral idiopathic hyperaldosteronism (IHA), a subtype of PA. METHODS: Ninety-eight patients with bilateral IHA underwent bilateral SAAE between August 2022 and August 2023. Sixty-eight patients were followed up for up to 12 months. The study outcomes were evaluated using the criteria provided by the Primary Aldosteronism Surgical Outcome (PASO) guidelines. RESULTS: The mean reductions in systolic and diastolic blood pressure were 27.4 ± 21.3 mmHg and 23.1 ± 17.4 mmHg, respectively (p < 0.001). The rates of clinical success and biochemical success after adrenal artery ablation were 63.2% (43/68) and 39.7% (27/68), respectively. Overall, there were significant reductions in daily defined doses (DDD), aldosterone/renin ratio (ARR), and plasma aldosterone levels (p < 0.001). Plasma renin levels increased by a mean value of 10.4 ± 39.0 pg/mL (p = 0.049), and potassium levels increased by 0.40 ± 0.63 mmol/L (p < 0.001). No significant adverse events were reported during SAAE or the follow-up period of up to one year. Additionally, no abnormalities were detected by adrenal 68Ga-Pentixafor PET/CT scans before or after SAAE. CONCLUSION: Bilateral SAAE appears to lead to sustained improvements in blood pressure and biochemical parameters in patients with bilateral PA, with minimal adverse effects. This suggests that bilateral SAAE could serve as an effective alternative approach for treating bilateral IHA, potentially curing this condition.

Influence path of work-family conflict on primary care physicians' resignation intention: Data from a Chinese cross-sectional survey.

BACKGROUND: Primary care physicians and their teams are the leading force in constructing primary medical services, undertaking the critical responsibility of residents' essential health, and also related to realizing the national health goal. However, primary care physicians generally have a high turnover rate due to problems such as high work pressure, low salary levels, and limited career development. Therefore, exploring primary care physicians' resignation intentions plays a vital role in promoting the construction of primary care physicians' health service system. OBJECTIVE: This study explores the factors influencing the resignation intentions of primary care physicians, specifically examining the roles of work-family conflict, job satisfaction, professional identity, and emotional exhaustion. By understanding these dynamics, the research aims to inform strategies that can enhance the stability and effectiveness of primary care services, ultimately contributing to the improvement of public health infrastructure and achieving national health goals. This investigation will utilize structural equation modeling to analyze the interrelationships among the identified variables, thereby providing a comprehensive framework for addressing the high turnover rates among primary care physicians. METHODS: This study uses the work-family conflict, job satisfaction, professional identity, and emotional exhaustion scales. The data comes from a cross-sectional survey in Zhejiang Province, China, in 2022. Using SPSS 27 and Mplus8.3 software to analyze 1205 primary care physicians and their team members, the selected cases all answered the relevant questions of resignation intention. The potential relationship among work-family conflict, job satisfaction, professional identity, emotional exhaustion, and family doctor resignation intention was explored by constructing structural equations. RESULTS: Work-family conflict can directly and positively affect primary care physicians' resignation intention (ß = -0.546, p < 0.001). The results of the mediation model found that job satisfaction, professional identity, and emotional exhaustion were significantly related to work-family conflict, and primary care physicians' resignation intention has a significant mediating effect. It mainly includes six intermediary approaches: one is through the independent intermediary effect of job satisfaction; the second is through the independent intermediary effect of professional identity; the third is through the chain intermediary effect between Job satisfaction and professional identity; the fourth is through the intermediary effect of Job satisfaction and emotional exhaustion chain intermediary; fifth is through the chain intermediary of professional identity and emotional exhaustion; sixth is through the complex chain intermediary of job satisfaction, professional identity, and emotional exhaustion. CONCLUSION: Primary care physicians have a high score in resignation intention, which deserves continuous attention. Relevant department can help primary care physicians balance work and family roles, provide them with appropriate resources and rewards, as well as a good working environment and career development opportunities, to improve their job satisfaction and professional identity and reduce emotional exhaustion, thereby reducing the risk of resignation intention.

Hypermethylation of the FOXP3 gene regulates Tregs immunodysregulation in chronic idiopathic thrombocytopenic purpura.

BACKGROUND: Chronic idiopathic thrombocytopenic purpura (ITP) is an autoimmune disease characterized by a breakdown of immune tolerance; in ITP, the body's immune system mistakenly attacks and destroys platelets. This study aims to investigate the role and underlying mechanisms of FOXP3 in chronic ITP. METHODS: Flow cytometry was used to detect the proportion of CD4+CD25+FOXP3+ regulatory T cells (Tregs) in CD4+CD25+ T lymphocytes from 20 patients with chronic ITP (CITP), 20 acute ITP (AITP) controls, and 20 healthy individuals.CD4+CD25+ Treg cells were isolated from peripheral blood of patients with CITP using magnetic beads and then treated with phosphate-buffered saline solution or decitabine (a methylation inhibitor) for 48 h. The levels of interleukin-2 (IL-2), IL-10, and transforming growth factor-beta1 (TGF-ß1) in the plasma and CD4+CD25+ Treg cells were assessed by Enzyme-linked-immunosorbent serologic assay and quantitative real-time polymerase chain reaction (qRT-PCR). FOXP3 level was measured by qRT-PCR and Western blot analysis. Methylation-specific PCR (MS-PCR) was adopted to detect the status of FOXP3 methylation. RESULTS: The number of Treg cells and the contents of IL-2, IL-10, and TGF-ß1 decreased in patients with CITP, compared to the AITP control group and normal group. FOXP3 expression was reduced and FOXP3 methylation increased in patients with CITP, compared to the AITP control group and normal group. Hypermethylation of FOXP3 promoter led to decrease in FOXP3 level in Treg cells. Inhibition of FOXP3 promoter hypermethylation promoted the secretion of IL-2, IL-10, and TGF-ß1 in Treg cells. CONCLUSION: The number of Treg cells in CITP patients decreased, and the hypermethylation of FOXP3 promoter led to reduction of its expression in Treg cells, thus affecting the immune functioning of Treg cells.

Investigating the Sole Olefin-Based Cycle in Small-Cage MCM-35-Catalyzed Methanol-to-Olefins Reactions.

Small-pore zeolites catalyze the methanol-to-olefins (MTO) reaction via a dual-cycle mechanism, encompassing both olefin- and aromatic-based cycles. Zeolite topology is crucial in determining both the catalytic pathway and the product selectivity of the MTO reaction. Herein, we investigate the mechanistic influence of MCM-35 zeolite on the MTO process. The structural properties of the as-synthesized MCM-35 catalyst, including its confined cages (6.19 Å), were characterized, confirming them as the catalytic centers. Then, the MTO reactions were systematically performed and investigated over a MCM-35 catalyst. Feeding pure methanol to the reactor yielded minimal MTO activity despite the formation of some aromatic species within the zeolite. The results suggest that the aromatic-based cycle is entirely suppressed in MCM-35, preventing the simultaneous occurrence of the olefin-based cycle. However, cofeeding a small amount of propene in methanol can obviously enhance the methanol conversion under the same studied reaction conditions. Thus, the exclusive operation of the olefin-based cycle in the MTO reaction, independent of the aromatic-based cycle, was demonstrated in MCM-35 zeolite.

Frontal and parietal cortices activation during walking is repeatable in older adults based on fNIRS.

Purpose: This study aimed to explore the test-retest reliability of fNIRS in measuring frontal and parietal cortices activation during straight walking and turning walking in older adults, in order to provide a theoretical foundation for selecting assessment tools for clinical research on motor control and some diseases such as Parkinson's disease in older adults. Methods: 18 healthy older participants (69.1 ± 0.7 years) were included in this study. The participants completed straight walking and figure-of-eight turning walking tasks at self-selected speeds. Intra-class correlation coefficients (ICCs) and Bland-Altman scatter plots were used to assess the test-retest reliability of oxyhemoglobin (HbO2) changes derived from fNIRS. p < 0.05 was considered statistically significant. Results: The test-retest reliability of HbO2 in prefrontal cortex (ICC, 0.67-0.78) was good and excellent, in frontal motor cortex (ICC, 0.51-0.61) and parietal sensory cortex (ICC, 0.53-0.62) is fair and good when the older adults performed straight and turning walking tasks. Bland-Altman diagram shows that the data consistency is fair and good. Conclusion: fNIRS can be used as a clinical measurement method to evaluate the brain activation of the older adults when walking in a straight line and turning, and the results are acceptable repeatability and consistency. However, it is necessary to strictly control the testing process and consider the possible changes in the repeated measurements.

[Modified QuEChERS method combined with ultra performance liquid chromatography-tandem mass spectrometry for detection of cyclopiazonic acid in feeds].

Mycotoxins are toxic secondary metabolites produced by fungal species that can cause acute, subacute, and chronic toxicity in humans and animals. Thus, these toxins pose a significant threat to health and safety. Owing to the lack of effective antimold measures in the agricultural industry, feed ingredients such as corn, peanuts, wheat, barley, millet, nuts, oily feed, forage, and their byproducts are prone to mold and mycotoxin contamination, which can affect animal production, product quality, and safety. Cyclopiazonic acid (CPA), which is mainly biosynthesized from mevalonate, tryptophan, and diacetate units, is a myotoxic secondary metabolite produced by Penicillium and Aspergillus fungi. CPA is widely present as a copollutant with aflatoxins in various crops. Compared with some common mycotoxins such as aflatoxins, fumonisins, ochratoxins, zearalenones, and their metabolites, CPA has not been well investigated. In the United States, a survey showed that 51% of corn and 90% of peanut samples contained CPA, with a maximum level of 2.9 mg/kg. In Europe, CPA was found in Penicillium-contaminated cheeses as high as 4.0 mg/kg. Some studies have shown that CPA can cause irreversible damage to organs such as the liver and spleen in mice. Therefore, the establishment of a rapid and efficient analytical method for CPA is of great significance for the risk assessment of CPA in feeds, the development of standard limits, and the protection of feed product quality and safety. The QuEChERS method, a sample pretreatment method that is fast, simple, cheap, effective, and safe, is widely used in the analysis of pesticide residues in food. In this study, a modified QuEChERS method combined with ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to determine CPA levels in feeds. The chromatographic separation and MS detection of CPA as well as the key factors affecting the extraction efficiency of CPA, including the type of extraction solvent, type of inorganic salt, and type and dosage of adsorbent, were optimized in detail. During the optimization of the chromatographic-separation step, the acid and salt concentrations of the mobile phase affected the separation and detection of CPA. During the optimization of the QuEChERS method, the addition of a certain amount of acetic acid improved the extraction efficiency of CPA because of its acidic nature; in addition, GCB and PSA significantly adsorbed CPA from the feed extract. Under optimal conditions, the CPA in the feed sample (1.0 g) was extracted with 2 mL of water and 4 mL of acetonitrile (ACN) containing 0.5% acetic acid. After salting out with 0.4 g of NaCl and 1.6 g of MgSO4, 1 mL of the ACN supernatant was purified by dispersive solid-phase extraction using 150 mg of MgSO4 and 50 mg of C18 and analyzed by UPLC-MS/MS. The sample was separated on a Waters HSS T3 column (100 mm×2.1 mm, 1.8 µm) using 2 mmol/L ammonium acetate aqueous solution with 0.5% formic acid and ACN as the mobile phases and then analyzed by positive electrospray ionization in multiple reaction monitoring mode. CPA exhibited good linearity in the range of 2-200 ng/mL, with a high correlation coefficient (r=0.9995). The limits of detection and quantification of CPA, which were calculated as 3 and 10 times the signal-to-noise ratio, respectively, were 0.6 and 2.0 µg/kg, respectively. The average recoveries in feed samples spiked with 10, 100, and 500 µg/kg CPA ranged from 70.1% to 78.5%, with an intra-day precision of less than 5.8% and an inter-day precision of less than 7.2%, indicating the good accuracy and precision of the proposed method. Finally, the modified QuEChERS-UPLC-MS/MS method was applied to the analysis of CPA in 10 feed samples obtained from Wuhan market. The analysis results indicated that the developed method has good applicability for CPA analysis in feed samples. In summary, an improved QuEChERS method was applied to the extraction and purification of CPA from feeds for the first time; this method provides a suitable analytical method for the risk monitoring, assessment, and standard-limit setting of CPA in feed samples.

Anthracycline-induced arrhythmias in breast cancer therapy: A meta-analysis of single-arm trials.

INTRODUCTION: As of 2020, breast cancer has emerged as the predominant cause of cancer incidence globally. Anthracycline-based chemotherapy serves as a crucial element in the treatment regimen for breast cancer. However, these anthracycline-based drugs are associated with cardiac toxicity. This study represents the first clinical quantitative analysis aimed at accurately determining the incidences of arrhythmia and abnormal electrocardiogram (ECG) changes, thereby providing valuable data to bolster clinical drug usage and monitoring. METHODS: A systematic search was conducted across multiple databases including CNKI, VIP, Wanfang, PubMed, Embase, Web of Science, and the Cochrane Library. The incidence of combined arrhythmias in breast cancer patients and the associated heterogeneity were calculated using either a random effect model or a fixed effect model. Statistical analysis was performed using STATA16. RESULTS: The study encompassed a total of 37 articles, which included 5705 breast cancer patients undergoing anthracycline treatment. Among these patients, 2257 developed arrhythmias. The meta-analysis revealed that the incidence of anthracycline-associated arrhythmias and abnormal ECG changes in breast cancer patients was 0.41 (0.37, 0.44). Subgroup analysis indicated that the incidence of ST-T segment change was 0.19 (0.15, 0.23), the incidence of conduction block was 0.04 (0.02, 0.05), the incidence of premature beats was 0.09 (0.07, 0.11), and the incidence of atrial fibrillation was 0.04 (0.00, 0.12). Additional results are presented in Table 3. CONCLUSION: This pioneering study accurately assesses the incidence of arrhythmias in breast cancer patients treated with anthracyclines. The findings provide clinicians with valuable insights into understanding and managing the cardiac toxicity associated with such treatment. Moreover, this study lays the foundation for future research exploring the mechanisms underlying these arrhythmias and potential preventative strategies.

Identification of hypoxic macrophages in glioblastoma with therapeutic potential for vasculature normalization.

Monocyte-derived tumor-associated macrophages (Mo-TAMs) intensively infiltrate diffuse gliomas with remarkable heterogeneity. Using single-cell transcriptomics, we chart a spatially resolved transcriptional landscape of Mo-TAMs across 51 patients with isocitrate dehydrogenase (IDH)-wild-type glioblastomas or IDH-mutant gliomas. We characterize a Mo-TAM subset that is localized to the peri-necrotic niche and skewed by hypoxic niche cues to acquire a hypoxia response signature. Hypoxia-TAM destabilizes endothelial adherens junctions by activating adrenomedullin paracrine signaling, thereby stimulating a hyperpermeable neovasculature that hampers drug delivery in glioblastoma xenografts. Accordingly, genetic ablation or pharmacological blockade of adrenomedullin produced by Hypoxia-TAM restores vascular integrity, improves intratumoral concentration of the anti-tumor agent dabrafenib, and achieves combinatorial therapeutic benefits. Increased proportion of Hypoxia-TAM or adrenomedullin expression is predictive of tumor vessel hyperpermeability and a worse prognosis of glioblastoma. Our findings highlight Mo-TAM diversity and spatial niche-steered Mo-TAM reprogramming in diffuse gliomas and indicate potential therapeutics targeting Hypoxia-TAM to normalize tumor vasculature.

Highly Efficient One-pot Electrosynthesis of Oxime Ethers from NOx over Ultrafine MgO Nanoparticles Derived from Mg-based Metal-Organic Frameworks.

Oxime ethers are attractive compounds in medicinal scaffolds due to the biological and pharmaceutical properties, however, the crucial and widespread step of industrial oxime formation using explosive hydroxylamine (NH2OH) is insecure and troublesome. Herein, we present a convenient method of oxime ether synthesis in a one-pot tandem electrochemical system using magnesium based metal-organic framework-derived magnesium oxide anchoring in self-supporting carbon nanofiber membrane catalyst (MgO-SCM), the in situ produced NH2OH from nitrogen oxides electrocatalytic reduction coupled with aldehyde to produce 4-cyanobenzaldoxime with a selectivity of 93 % and Faraday efficiency up to 65.1 %, which further reacted with benzyl bromide to directly give oxime ether precipitate with a purity of 97 % by convenient filtering separation. The high efficiency was attributed to the ultrafine MgO nanoparticles in MgO-SCM, effectively inhibiting hydrogen evolution reaction and accelerating the production of NH2OH, which rapidly attacked carbonyl of aldehydes to form oximes, but hardly crossed the hydrogenation barrier of forming amines, thus leading to a high yield of oxime ether when coupling benzyl bromide nucleophilic reaction. This work highlights the importance of kinetic control in complex electrosynthetic organonitrogen system and demonstrates a green and safe alternative method for synthesis of organic nitrogen drug molecules.

Homeobox B2 promotes malignant behavior and contributes to the radioresistance of nasopharyngeal carcinoma by regulating forkhead box protein O1.

Background: Nasopharyngeal carcinoma (NPC) is an epithelial tumor of the head and neck with heterogeneous racial and geographical distributions. Homeobox B2 (HOXB2) is a tumor promoter in many cancers. However, the biological role of HOXB2 in NPC has not been elucidated. Methods: Bioinformatics analysis was performed to identify the differentially expressed genes (DEGs) between samples of patients with radiosensitive and radioresistant NPC. qRT-PCR, western blotting and immunohistochemistry were used to detect the expression levels of the corresponding mRNA and proteins. Cell viability was detected by CCK-8 assay and colony-forming capability was evaluated using colony formation assays. Further, migration and invasion abilities were examined using wound-healing and transwell chamber assays, respectively. Cellular apoptosis after irradiation was assessed using flow cytometry and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining. Results: HOXB2 was identified as a potential regulator of radioresistance in NPC. Our in vitro results indicate that HOXB2 overexpression (HOXB2-OE) promoted malignant behaviors including invasion, migration, proliferation, and inhibited the irradiation-induced apoptosis of NPC cells. Consistent with these results, HOXB2 knockdown (HOXB2-sh) exhibited the opposite trends in these biological activities. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the DEGs were enriched in the FOXO signaling pathway. Mechanistically, western blotting showed that HOXB2-OE inhibited forkhead box protein O1 (FOXO1) expression in NPC cells. Thereafter, we transferred the FOXO1-OE plasmid to HOXB2-OE NPC cells and found that overexpression of FOXO1 reversed cell proliferation, migration, invasion, and radioresistance profiles promoted by HOXB2 overexpression. Conclusion: Our findings showed that HOXB2 acts as a tumor promoter in NPC, activating malignant behaviors and radioresistance of tumors via FOXO1 regulation. Moreover, the inactivation of HOXB2 or activation of FOXO1 are potential strategies to inhibit tumor progression and overcome radioresistance in NPC.

The effect of Tai Chi lower extremity exercise on the balance control of older adults in assistant living communities.

BACKGROUND: Although Tai Chi (TC) is an evidence-based fall prevention training for older adults, its effective movements remain unclear, which may limit the practice of TC. The purpose of this study was to compare the effectiveness of TC lower extremity exercise (TC LEE), the 8-form Tai Chi (8-form TC), and a stretching control intervention for improving balance and functional mobility among older adults. METHODS: This was a randomized controlled trial. A total of 102 participants (79 ± 6 years old) were recruited from assisted living facilities. All participants were randomly assigned to the TC LEE (n = 40), 8-form TC (n = 31), and stretching (n = 31) groups in which they received the respective interventions for 16 weeks. The Berg Balance Scale (BBS), Timed Up and Go (TUG) test, and center of pressure (COP) measurements during quiet stance were collected prior to and following the 16-week interventions. Comparisons on all measurements were conducted among all groups. RESULTS: Significant improvements were found in BBS (P = 0.002), TUG test (P = 0.001), root mean square amplitude of COP displacement in the anterior-posterior (P = 0.001) and medial-lateral (P = 0.001) directions, and average COP speed in the anterior-posterior (P = 0.001) and medial-lateral (P = 0.001) directions after training in the TC intervention groups compared with the stretching group. The upper limit of the 95% confidence interval (CI) of differences in change scores on the BBS (-0.8 - 1.3 points) between the TC LEE group and the 8-form TC group was within equivalence margins (1.8 points), while the upper limit of the 95% CI of differences in change scores on the TUG test (0.1 - 2.1 s) exceeded the equivalence margin (0.7 s) with the TC LEE group having the larger change scores. CONCLUSION: TC LEE can improve balance and functional mobility in older adults, and may have greater effect than the 8-form TC on improving functional mobility as measured by the TUG test. TRIAL REGISTRATION: ChiCTR2300070600 retrospectively registered.

Tai Chi counteracts age-related somatosensation and postural control declines among older adults.

Objective: To investigate the effect of a 16-week Tai Chi practice on strength, tactile sensation, kinesthesia, and static postural control among older adults of different age groups. Methods: This is a quasi-experimental study. Thirteen participants aged 60-69 years (60-69yr), 11 aged 70-79 years (70-79yr), and 13 aged 80-89 years (80-89yr) completed 16 weeks of 24-form Tai Chi practice. Their ankle and hip peak torque, tactile sensation, ankle and knee kinesthesia, and the root mean square of the center of pressure (Cop-RMS) were measured before (week 0) and after (week 17) practice. Results: 80-89yr showed less ankle plantar/dorsiflexion and hip abduction peak torques (p = 0.003, p < 0.001, p = 0.001), and a greater ankle plantar/dorsiflexion kinesthesia (p < 0.001, p = 0.002) than 60-69yr and 70-79yr. Greater ankle plantar/dorsiflexion and hip abduction torques (p = 0.011, p < 0.001, p = 0.045), improved arch and heel tactile sensation (p = 0.040, p = 0.009), and lower knee flexion/extension kinesthesia (p < 0.001, p = 0.044) were observed at week 17. The significant group*practice interaction for the fifth metatarsal head tactile sensation (p = 0.027), ankle plantar/dorsiflexion kinesthesia (p < 0.001, p = 0.004), and the CoP-RMS in the mediolateral direction (p = 0.047) only in 80-89yr revealed greater improvement at week 17. Conclusion: Tai Chi practice increased strength, tactile sensation, kinesthesia, and static postural control among older adults. Tai Chi practice improved tactile, kinesthesia sensations, and static postural control among older adults over 80, who presented with worse strength and kinesthesia than their younger counterparts. Tai Chi practice offers a safe exercise option for those aged over 80 to encourage improvements in sensorimotor control.

Reclassified the phenotypes of cancer types and construct a nomogram for predicting bone metastasis risk: A pan-cancer analysis.

BACKGROUND: Numerous of models have been developed to predict the bone metastasis (BM) risk; however, due to the variety of cancer types, it is difficult for clinicians to use these models efficiently. We aimed to perform the pan-cancer analysis to create the cancer classification system for BM, and construct the nomogram for predicting the BM risk. METHODS: Cancer patients diagnosed between 2010 and 2018 in the Surveillance, Epidemiology, and End Results (SEER) database were included. Unsupervised hierarchical clustering analysis was performed to create the BM prevalence-based cancer classification system (BM-CCS). Multivariable logistic regression was applied to investigate the possible associated factors for BM and construct a nomogram for BM risk prediction. The patients diagnosed between 2017 and 2018 were selected for validating the performance of the BM-CCS and the nomogram, respectively. RESULTS: A total of 50 cancer types with 2,438,680 patients were included in the construction model. Unsupervised hierarchical clustering analysis classified the 50 cancer types into three main phenotypes, namely, categories A, B, and C. The pooled BM prevalence in category A (17.7%; 95% CI: 17.5%-17.8%) was significantly higher than that in category B (5.0%; 95% CI: 4.5%-5.6%), and category C (1.2%; 95% CI: 1.1%-1.4%) (p < 0.001). Advanced age, male gender, race, poorly differentiated grade, higher T, N stage, and brain, lung, liver metastasis were significantly associated with BM risk, but the results were not consistent across all cancers. Based on these factors and BM-CCS, we constructed a nomogram for predicting the BM risk. The nomogram showed good calibration and discrimination ability (AUC in validation cohort = 88%,95% CI: 87.4%-88.5%; AUC in construction cohort = 86.9%,95% CI: 86.8%-87.1%). The decision curve analysis also demonstrated the clinical usefulness. CONCLUSION: The classification system and prediction nomogram may guide the cancer management and individualized BM screening, thus allocating the medical resources to cancer patients. Moreover, it may also have important implications for studying the etiology of BM.

Sacubitril/valsartan can improve the cardiac function in heart failure patients with a history of cancer: An observational study.

Sacubitril/Valsartan, the combination of angiotensin receptor inhibitor and neprilysin inhibitor, is now becoming the class 1 recommendation for HFrEF. Some studies have shown the positive effect of Sacubitril/Valsartan on HFrEF cancer patients, while there is devoid of evidence about the effect of this drug in aged cancer patients with HFmrEF and HFpEF. By searching the patients with a diagnosis of both cancer and Heart failure (HF) over 65, the patients who had received treatment with Sacubitril/Valsartan were selected as the candidates for Sacubitril/Valsartan group, and the patients who had received conventional HF therapy without Sacubitril/Valsartan were chosen as the control group. Data were collected for up to 9 months. We filtered 38 patients and 50 patients valid for Sacubitril/Valsartan group and control group, respectively. After initiation of heart failure management, our study found a better cardiac condition in Sacubitril/Valsartan group, having better LVEF, LVFS, NT-proBNP in 3rd, 6th, 9th month (P < .05) and better NYHA function classification after the treatment. We also observed fewer cases of deterioration on LAD (P = .029) and LVEDD (P = .023) in Sacubitril/Valsartan group. In subgroup analysis, our study showed that all 3 kinds of HF patients had better LVEF, LVFS, and NT-proBNP in Sacubitril/Valsartan group (P < .05). Our study further indicated that Sacubitril/Valsartan can improve cardiac function and benefit cardiac remolding in aged cancer patients of all 3 kinds of HF. This is the first study to provide new evidence for the use of Sacubitril/Valsartan in aged cancer patients of 3 kinds of HF.

Renin-angiotensin-aldosterone-system inhibitors increase the serum level of complement component 4 in patients with immunoglobulin A nephropathy.

OBJECTIVE: To investigate the impact of renin-angiotensin-aldosterone-system (RAAS) inhibitors on complement component 4 (C4) serum levels in patients with immunoglobulin A nephropathy (IgAN). METHODS: A total of 423 patients diagnosed with IgAN at Shanxi Provincial People's Hospital, China, between 1 January 2017 and 31 December 2021 were divided into two groups, a RAAS inhibitor group and a non-RAAS inhibitor group, for comparative analysis. RESULTS: The RAAS inhibitor group exhibited significantly increased C4 and eGFR levels and had a higher proportion of patients with hypertension compared with the non-RAAS inhibitor group. Serum C4 levels were positively correlated with 24-hour urine protein, serum C3 levels and blood uric acid levels but negatively correlated with eGFR levels. In addition, serum C4 levels were positively correlated with the severity of mesangial hypercellularity and interstitial/tubular injury. Through prognostic analysis, serum C4 was identified as an independent risk factor for the progression of IgAN. CONCLUSION: Renin-angiotensin-aldosterone-system inhibitors can increase serum C4 levels in patients with IgAN and may represent an independent risk factor for disease progression.