Discovery of A G-Quadruplex Unwinder That Unleashes the Translation of G-Quadruplex-Containing mRNA without Inducing DNA Damage.

To explore the mechanisms and therapeutic strategies for G-quadruplex (G4) mediated diseases, it is crucial to manipulate and intervene in intracellular G4 structures using small molecular tools. While hundreds of G4 stabilizers have been developed, there is a significant gap in the availability of G4 unwinding agents. Here, we propose a strategy to disrupt G-quadruplexes by forming G-C hydrogen bonds with chemically modified cytidine trimers. We validated a good G4 unwinder, the 2'-F cytidine trimer (2'-F C3). 2'-F C3 does not inhibit cell growth nor cause severe DNA damage at a concentration below 10 µM. Moreover, 2'-F C3 does not affect gene transcription nor RNA splicing, while it significantly enhances the translation of G4-containing mRNA and upregulates RNA splicing, RNA processing and cell cycle pathways. The discovery of this G4 unwinder provides a functional tool for the chemical modulation of G4s in living cells.

Effects of minimally invasive surgery combined with specialized pain management nursing care on postoperativepain improvement and life quality after spinal injury.

Objective: To determine the impacts to research the impacts of pain's Specialized Pain Management Nursing Care in the perioperative period on pain symptoms and life quality of patients experiencing minimally invasive surgery for spinal injury. Method: Eighty patients with a spinal injury who underwent minimally invasive surgery in the Department of Orthopedics of Baoding No.1 Hospital from January 2018 to December 2021 were retrospectively analyzed. They were split into two groups following different nursing methods (n=40 each group). Specialized Pain Management Nursing Care were given to patients in the observation group. Those in the control group were given treated with routine care. Their pain score and nursing effect were compared, after which their quality of life, daily living ability and complication rate compared and analyzed. Results: The pain degree in the control group was considerably more than that in the observation group in the 1st postoperative period. The pain degree, which decreased in both groups, slumped more significantly in the observation group on the 2nd and 3rd postoperative days. The postoperative hospital stays and pain duration in the observation group were shorter than those in the control group (P<0.05), and the nursing effect was significantly better than that in the control group (P<0.05). After postoperative nursing intervention. Conclusion: Minimally invasive surgery integrated with the Specialized Pain Management Nursing Care can remarkably ameliorate pain after spinal injury surgery, reducing complications' incidence, and improving the life quality for patients.

Evaluating the associations between intelligence quotient and multi-tissue proteome from the brain, CSF and plasma.

Intelligence quotient is a vital index to evaluate the ability of an individual to think rationally, learn from experience and deal with the environment effectively. However, limited efforts have been paid to explore the potential associations of intelligence quotient traits with the tissue proteins from the brain, CSF and plasma. The information of protein quantitative trait loci was collected from a recently released genome-wide association study conducted on quantification data of proteins from the tissues including the brain, CSF and plasma. Using the individual-level genotypic data from the UK Biobank cohort, we calculated the polygenic risk scores for each protein based on the protein quantitative trait locus data sets above. Then, Pearson correlation analysis was applied to evaluate the relationships between intelligence quotient traits (including 120 330 subjects for 'fluid intelligence score' and 38 949 subjects for 'maximum digits remembered correctly') and polygenic risk scores of each protein in the brain (17 protein polygenic risk scores), CSF (116 protein polygenic risk scores) and plasma (59 protein polygenic risk scores). The Bonferroni corrected P-value threshold was P < 1.30 × 10-4 (0.05/384). Finally, Mendelian randomization analysis was conducted to test the causal relationships between 'fluid intelligence score' and pre-specific proteins from correlation analysis results. Pearson correlation analysis identified significant association signals between the protein of macrophage-stimulating protein and fluid intelligence in brain and CSF tissues (P brain = 1.21 × 10-8, P CSF = 1.10 × 10-7), as well as between B-cell lymphoma 6 protein and fluid intelligence in CSF (P CSF = 1.23 × 10-4). Other proteins showed close-to-significant associations with the trait of 'fluid intelligence score', such as plasma protease C1 inhibitor (P CSF = 4.19 × 10-4, P plasma = 6.97 × 10-4), and with the trait of 'maximum digits remembered correctly', such as tenascin (P plasma = 3.42 × 10-4). Additionally, Mendelian randomization analysis results suggested that macrophage-stimulating protein (Mendelian randomization-Egger: ß = 0.54, P = 1.64 × 10-61 in the brain; ß = 0.09, P = 1.60 × 10-12 in CSF) had causal effects on fluid intelligence score. We observed functional relevance of specific tissue proteins to intelligence quotient and identified several candidate proteins, such as macrophage-stimulating protein. This study provided a novel insight to the relationship between tissue proteins and intelligence quotient traits.

Effect of ozone treatment on phenylpropanoid metabolism in harvested cantaloupes.

Phenylpropanoid metabolism plays an important role in cantaloupe ripening and senescence, but the mechanism of ozone regulation on phenylpropanoid metabolism remains unclear. This study investigated how ozone treatment modulates the levels of secondary metabolites associated with phenylpropanoid metabolism, the related enzyme activities, and gene expression in cantaloupe. Treating cantaloupes with 15 mg/m3 of ozone after precooling can help maintain postharvest hardness. This treatment also enhances the production and accumulation of secondary metabolites, such as total phenols, flavonoids, and lignin. These metabolites are essential components of the phenylpropanoid metabolic pathway, activating enzymes like phenylalanine ammonia-lyase, cinnamate 4-hydroxylase, 4CL, chalcone synthase, and chalcone isomerase. The results of the transcriptional expression patterns showed that differential gene expression related to phenylpropanoid metabolism in the peel of ozone-treated cantaloupes was primarily observed during the middle and late storage stages. In contrast, the pulp exhibited significant differential gene expression mainly during the early storage stage. Furthermore, it was observed that the level of gene expression in the peel was generally higher than that in the pulp. The correlation between the relative amount of gene changes in cantaloupe, activity of selected enzymes, and concentration of secondary metabolites could be accompanied by positive regulation of the phenylpropanoid metabolic pathway. Therefore, ozone stress induction positively enhances the biosynthesis of flavonoids in cantaloupes, leading to an increased accumulation of secondary metabolites. Additionally, it also improves the postharvest storage quality of cantaloupes.

Ursodeoxycholic acid and COVID-19 outcomes: a cohort study and data synthesis of state-of-art evidence.

BACKGROUND: The potential of ursodeoxycholic acid (UDCA) in inhibiting angiotensin-converting enzyme 2 was demonstrated. However, conflicting evidence emerged regarding the association between UDCA and COVID-19 outcomes, prompting the need for a comprehensive investigation. RESEARCH DESIGN AND METHODS: Patients diagnosed with COVID-19 infection were retrospectively analyzed and divided into two groups: the UDCA-treated group and the control group. Kaplan-Meier recovery analysis and Cox proportional hazards models were used to evaluate the recovery time and hazard ratios. Additionally, study-level pooled analyses for multiple clinical outcomes were performed. RESULTS: In the 115-patient cohort, UDCA treatment was significantly associated with a reduced recovery time. The subgroup analysis suggests that the 300 mg subgroup had a significant (adjusted hazard ratio: 1.63 [95% CI, 1.01 to 2.60]) benefit with a shorter duration of fever. The results of pooled analyses also show that UDCA treatment can significantly reduce the incidence of severe/critical diseases in COVID-19 (adjusted odds ratio: 0.68 [95% CI, 0.50 to 0.94]). CONCLUSIONS: UDCA treatment notably improves the recovery time following an Omicron strain infection without observed safety concerns. These promising results advocate for UDCA as a viable treatment for COVID-19, paving the way for further large-scale and prospective research to explore the full potential of UDCA.

Nonclinical safety and immunogenicity assessment of a combined DTacP vaccine in animal models.

The (diphtheria, tetanus, and pertussis [acellular, component] [DTacP]) vaccine is a combined vaccine designed to prevent three potentially fatal diseases including pertussis, tetanus, and diphtheria in both children and adults. We utilized advanced technology to develop a novel DTacP vaccine that was previously unavailable in China. The nonclinical studies were performed to evaluate the immunogenicity, potential toxicity, and local tolerance of the vaccine in animal models. In the immunogenicity study, three batches of the vaccine were intraperitoneally administered to National Institutes of Health (NIH) mice, resulting in 100% seropositivity for all three batches. Additionally, antibody levels notably increased as the immunization dosage increased. In acute toxicity study, no mortality was observed among the animals during the 14-day observation period, and no abnormalities in clinical signs were reported. Active systemic anaphylaxis assessment in guinea pigs showed no evidence of serious allergic reactions in the vaccine groups. In the repeat-dose toxicity study, where five intramuscular doses were administered every 2 weeks, gross autopsy and histopathological examination revealed no vaccine-related systemic pathological changes in rats, with dose site irritant reactions mostly recovered at the end of recovery period. In conclusion, the vaccine demonstrated good local and systemic tolerance, supporting its clinical development.

High freeze-thaw stability of Pickering emulsion stabilized by SPI-maltose particles and its effect on frozen dough.

Pickering emulsions with good freeze-thaw stability are essential in frozen food applications. This study developed a high freeze-thaw stabilized soy protein isolate (SPI)-maltose (M) Pickering emulsion and applied it to frozen doughs to investigate and reveal its impacts on the processing properties of the frozen dough. The results showed that after the freeze-thaw cycle, with a volume ratio of 1:2 of SPI to M, the appropriate amount of M changed the structure of SPI. This resulted in the Pickering emulsion prepared by the SPI exhibiting the least droplet coalescence and the best freeze-thaw stability. The results of dough rheological properties, textural properties, and binding capacity with water demonstrated that Pickering emulsions effectively inhibited the loss of gluten protein network structure in the dough after freeze treatment and increased the binding capacity of gluten proteins with starch and water in the dough. The best results were obtained with the incorporation of 3 % SPI-M high freeze-thaw stability, where the amount of bound water following three freeze-thaw cycles was 4.27 times higher than in doughs without Pickering emulsion. Overall, this study is significant for enhancing the freeze-thaw stability of Pickering emulsions stabilized by proteins and providing a new application route for Pickering emulsions.

Lactate modulates zygotic genome activation through H3K18 lactylation rather than H3K27 acetylation.

In spite of its essential role in culture media, the precise influence of lactate on early mouse embryonic development remains elusive. Previous studies have implicated lactate accumulation in medium affecting histone acetylation. Recent research has underscored lactate-derived histone lactylation as a novel epigenetic modification in diverse cellular processes and diseases. Our investigation demonstrated that the absence of sodium lactate in the medium resulted in a pronounced 2-cell arrest at the late G2 phase in embryos. RNA-seq analysis revealed that the absence of sodium lactate significantly impaired the maternal-to-zygotic transition (MZT), particularly in zygotic gene activation (ZGA). Investigations were conducted employing Cut&Tag assays targeting the well-studied histone acetylation and lactylation sites, H3K18la and H3K27ac, respectively. The findings revealed a noticeable reduction in H3K18la modification under lactate deficiency, and this alteration showed a significant correlation with changes in gene expression. In contrast, H3K27ac exhibited minimal correlation. These results suggest that lactate may preferentially influence early embryonic development through H3K18la rather than H3K27ac modifications.

Effect of ultrafine grinding on the structure and physical properties of pregelatinized rice starch.

This study used a combination method of ultrafine grinding and pregelatinization to modify rice starch (RS) to delay its retrogradation and provide a rationale for prolonging rice product shelf life. The structure and physicochemical properties of the pregelatinized ultrafine grinding rice starch (PURS) were compared with those of RS, ultrafine grinding rice starch (URS), and pregelatinized rice starch (PRS). The microstructure, molecular weight, branched starch length distribution, short-range order, crystal structure, and physical properties of RS, URS, PRS, and PURS were analyzed, respectively. Results showed that RS, URS, PRS, and PURS granules exhibited similar spherical or polygonal shapes, and the content of amylose and short-branched starch in PURS increased compared with RS, URS, and PRS. Furthermore, the cross-polarization of PRS and PURS disappeared. Long-chain amylopectin and average molecular weight of PURS decreased significantly after ultrafine grinding. Our study suggested reduced breakdown value and setback value and improved gel stability, and PURS was beneficial for delaying retrogradation compared to RS, URS, and PRS. The ultrafine grinding method improved the water swelling capacity (WSC), solubility, pasting properties, and gelation properties of PRS. The hardness of PURS was reduced by ultrafine grinding. These suggest that the combination of ultrafine grinding and pregelatinization could improve the properties of RS. Pearson's correlation analysis showed that the structure of PURS significantly influenced the physicochemical properties. The present study was helpful in better understanding the importance of ultrafine grinding in improving the anti-retrogradation of PURS and provided new insights into extending the shelf life of rice products by ultrafine grinding and pregelatinization.

Micronutrient-Associated Single Nucleotide Polymorphism and Mental Health: A Mendelian Randomization Study.

PURPOSE: Previous studies have demonstrated the link between micronutrients and mental health. However, it remains uncertain whether this connection is causal. We aim to investigate the potential causal effects of micronutrients on mental health based on linkage disequilibrium score (LDSC) regression and Mendelian randomization (MR) analysis. METHODS: Utilizing publicly available genome-wide association study (GWAS) summary datasets, we performed LDSC and MR analysis to identify candidate micronutrients with potential causal effects on mental health. Single nucleotide polymorphisms (SNPs) significantly linked with candidate micronutrients with a genome-wide significance level (p < 5 × 10-8) were selected as instrumental variables (IVs). To estimate the causal effect of candidate micronutrients on mental health, we employed inverse variance weighted (IVW) regression. Additionally, two sensitivity analyses, MR-Egger and weighted median, were performed to validate our results. RESULTS: We found evidence supporting significant causal associations between micronutrients and mental health. LDSC detected several candidate micronutrients, including serum iron (genetic correlation = -0.134, p = 0.032) and vitamin C (genetic correlation = -0.335, p < 0.001) for attention-deficit/hyperactivity disorder (ADHD), iron-binding capacity (genetic correlation = 0.210, p = 0.037) for Alzheimer's disease (AD), and vitamin B12 (genetic correlation = -0.178, p = 0.044) for major depressive disorder (MDD). Further MR analysis suggested a potential causal relationship between vitamin B12 and MDD (b = -0.139, p = 0.009). There was no significant heterogeneity or pleiotropy, indicating the validity of the findings. CONCLUSION: In this study, we identified underlying causal relationships between micronutrients and mental health. Notably, more research is necessary to clarify the underlying biological mechanisms by which micronutrients affect mental health.

Body shape from birth to adulthood is associated with skeletal development: A Mendelian randomization study.

BACKGROUND: Observational studies have shown that childhood obesity is associated with adult bone health but yield inconsistent results. We aimed to explore the potential causal association between body shape and skeletal development. METHODS: We used two-sample Mendelian randomization (MR) to estimate causal relationships between body shape from birth to adulthood and skeletal phenotypes, with exposures including placental weight, birth weight, childhood obesity, BMI, lean mass, fat mass, waist circumference, and hip circumference. Independent genetic instruments associated with the exposures at the genome-wide significance level (P < 5 × 10-8) were selected from corresponding large-scale genome-wide association studies. The inverse-variance weighted analysis was chosen as the primary method, and complementary MR analyses included the weighted median, MR-Egger, weighted mode, and simple mode. RESULTS: The MR analysis shows strong evidence that childhood (ß = -1.29 × 10-3, P = 8.61 × 10-5) and adulthood BMI (ß = -1.28 × 10-3, P = 1.45 × 10-10) were associated with humerus length. Tibiofemoral angle was negatively associated with childhood BMI (ß = -3.60 × 10-1, P = 3.00 × 10-5) and adolescent BMI (ß = -3.62 × 10-1, P = 2.68 × 10-3). In addition, genetically predicted levels of appendicular lean mass (ß = 1.16 × 10-3, P = 1.49 × 10-13), whole body fat mass (ß = 1.66 × 10-3, P = 1.35 × 10-9), waist circumference (ß = 1.72 × 10-3, P = 6.93 × 10-8) and hip circumference (ß =1.28 × 10-3, P = 4.34 × 10-6) were all associated with tibia length. However, we found no causal association between placental weight, birth weight and bone length/width. CONCLUSIONS: This large-scale MR analysis explores changes in growth patterns in the length/width of major bone sites, highlighting the important role of childhood body shape in bone development and providing insights into factors that may drive bone maturation.

Discrepancies between self-reported medication in adherence and indirect measurement adherence among patients undergoing antiretroviral therapy: a systematic review.

BACKGROUND: Given the critical importance of medication adherence in HIV/AIDS treatment, this study aims to compare medication adherence measured by self-report (SR) and indirect measurement among antiretroviral therapy (ART) patients, exploring the differences of adherence results measured by different tools. METHODS: We systematically searched PubMed, Embase, and the Cochrane Library to identify all relevant literature published up to November 22, 2023, without language restrictions, reporting adherence to ART measured by both SR and indirect measurement methods, while also analyzing individual and group adherence separately. Discrepancies between SR and indirect measurement results were assessed using the Mann-Whitney U test or Wilcoxon signed-rank test, with correlations evaluated using the Pearson correlation coefficient. Following one-to-one comparisons, meta-epidemiological one-step analysis was conducted, and network meta-analysis techniques were applied to compare results obtained through specific adherence assessment tools reported in the identified articles. RESULTS: The analysis encompassed 65 original studies involving 13,667 HIV/AIDS patients, leading to 112 one-to-one comparisons between SR and indirect measurement tools. Statistically significant differences were observed between SR and indirect measurement tools regarding both individual and group adherence (P < 0.05), with Pearson correlation coefficients of 0.843 for individual adherence and 0.684 for group adherence. During meta-epidemiological one-step analysis, SR-measured adherence was determined to be 3.94% (95% CI: -4.48-13.44%) higher for individual adherence and 16.14% (95% CI: 0.81-18.84%) higher for group adherence compared to indirectly measured results. Subgroup analysis indicated that factors such as the year of reporting and geographic region appeared to influence the discrepancies between SR and indirect measurements. Furthermore, network meta-analysis revealed that for both individual and group adherence, the results obtained from most SR and indirect measurement tools were higher than those from electronic monitoring devices, with some demonstrating statistical significance (P < 0.05). CONCLUSIONS: The findings underscored the complexity of accurately measuring medication adherence among ART patients. Significant variability was observed across studies, with self-report methods showing a significant tendency towards overestimation. Year of reporting, geographic region, and adherence measurement tools appeared to influence the differences between SR and indirect measurements. Future research should focus on developing and validating integrated adherence measurements that can combine SR data with indirect measures to achieve a more comprehensive understanding of adherence behaviors.

Santalum album L. alleviates cardiac function injury in heart failure by synergistically inhibiting inflammation, oxidative stress and apoptosis through multiple components.

BACKGROUND: Heart failure (HF) is a complex cardiovascular syndrome with high mortality. Santalum album L. (SAL) is a traditional Chinese medicine broadly applied for various diseases treatment including HF. However, the potential active compounds and molecular mechanisms of SAL in HF treatment are not well understood. METHODS: The active compounds and possible mechanisms of action of SAL were analyzed and validated by a systems pharmacology framework and an ISO-induced mouse HF model. RESULTS: We initially confirmed that SAL alleviates heart damage in ISO-induced HF model. A total of 17 potentially active components in SAL were identified, with Luteolin (Lut) and Syringaldehyde (SYD) in SAL been identified as the most effective combination through probabilistic ensemble aggregation (PEA) analysis. These compounds, individually and in their combination (COMB), showed significant therapeutic effects on HF by targeting multiple pathways involved in anti-oxidation, anti-inflammation, and anti-apoptosis. The active ingredients in SAL effectively suppressed inflammatory mediators and pro-apoptotic proteins while enhancing the expression of anti-apoptotic factors and antioxidant markers. Furthermore, the synergistic effects of SAL on YAP and PI3K-AKT signaling pathways were further elucidated. CONCLUSIONS: Mechanistically, the anti-HF effect of SAL is responsible for the synergistic effect of anti-inflammation, antioxidation and anti-apoptosis, delineating a multi-targeted therapeutic strategy for HF.

Intracranial vasculopathy: an important organ damage in young adult patients with late-onset Pompe disease.

BACKGROUND: Late-onset Pompe disease (LOPD) is mainly characterized by progressive limb-girdle muscle weakness and respiratory impairment, whereas stroke and cerebrovascular abnormalities have been insufficiently studied in LOPD. This study aimed to evaluate the frequency and pattern of intracranial artery and brain parenchyma abnormalities in LOPD patients. RESULTS: Neuroimaging data from 30 Chinese adult LOPD patients were collected from our center. Seven patients (7/30) had acute cerebral infarction or hemorrhage. Brain magnetic resonance angiography (MRA) or computed tomography angiography (CTA) revealed artery abnormalities in 23 patients (23/30). Dilative arteriopathy was found in 19 patients (19/30), with vertebrobasilar dolichoectasia found in 17 patients and dilatation of the anterior circulation arteries found in 8 patients. The maximum diameter of the basilar artery was correlated with disease duration (p < 0.05). In addition, aneurysms (7/30) and fenestrations (3/30) were discovered. There were 14 patients with arterial stenosis (14/30), and both anterior and posterior circulation involvement occurred in 9 patients (9/14). Stenosis and dilative arteriopathy simultaneously occurred in 10 patients (10/30). White matter hyperintensities were present in 13 patients (13/28). Microbleeds, predominantly located in the cerebellum and brainstem, were detected in 7 patients (7/22) via susceptibility-weighted imaging. CONCLUSIONS: Intracranial vasculopathy involving both large arteries and small vessels is an important organ damage in LOPD patients. LOPD should be considered a key differential diagnosis in young adults with cryptogenic stroke, and a series of imaging evaluations of the brain and intracranial blood vessels is recommended as a routine workup in adult LOPD patients.

OTUB1 Promotes Glioblastoma Growth by Inhibiting the JAK2/STAT1 Signaling Pathway.

Background: OTUB1, an essential deubiquitinating enzyme, is upregulated in various types of cancer. Previous studies have shown that OTUB1 may be an oncogene in glioblastoma multiforme (GBM), but its specific regulatory mechanism remains unclear. This study aimed to investigate the mechanism by which OTUB1 and the JAK2/STAT1 signaling pathway co-regulate the growth of GBM. Methods: Using bioinformatics, GBM tissues, and cells, we evaluated the expression and clinical significance of OTUB1 in GBM. Subsequently, we explored the regulatory mechanisms of OTUB1 on malignant behaviors in GBM in vitro and in vivo. In addition, we added the JAK2 inhibitor AZD1480 to explore the regulation of OTUB1 for JAK2/STAT1 pathway in GBM. Results: We found that OTUB1 expression was upregulated in GBM. Silencing OTUB1 promotes apoptosis and cell cycle arrest at G1 phase, inhibiting cell proliferation. Moreover, OTUB1 knockdown effectively inhibited the invasion and migration of GBM cells, and the opposite phenomenon occurred with overexpression. In vivo experiments revealed that OTUB1 knockdown inhibited tumor growth, further emphasizing its crucial role in GBM progression. Mechanistically, we found that OTUB1 was negatively correlated with the JAK2/STAT1 pathway in GBM. The addition of the JAK2 inhibitor AZD1480 significantly reversed the effects of silencing OTUB1 on GBM. Conclusion: Our study reveals a novel mechanism by which OTUB1 inhibits the JAK2/STAT1 signaling pathway. This contributes to a better understanding of OTUB1's role in GBM and provides a potential avenue for targeted therapeutic intervention.

Towards food-derived self-assembling peptide-based hydrogels: Insights into preparation, characterization and mechanism.

Food proteins represent a vital source of self-assembling peptides, with hydrogels constructed through peptide self-assembly exhibiting widespread utility in the food sector. This review aims to provide a recent research progress in preparation and characterization of hydrogels from food-derived peptides. Also, the self-assembly mechanisms and the impact of factors are discussed. Presently, food-derived self-assembling peptide-based hydrogels can be synthesized using either physical or chemical methodologies and evaluated through methodologies such as microscopic, spectroscopic, and rheological assessment. The self-assembly of food-derived peptides is hierarchically formed by non-covalent interactions, including hydrogen bond and hydrophobic interactions, where variables such as temperature and pH intricately modulate the assembly mechanism. The association between peptide sequence and hydrogel structure in the self-assembly mechanism is also discussed, which remains to be further explored. The present review contributes to application of food-derived peptide-based hydrogels in the fields of food, nutrition and material sciences.

Effect of saline perfusion before catheter removal in patients with BPH treated with GreenLight laser photoselective vaporization of the prostate.

OBJECTIVE: To investigate the effect of saline perfusion before catheter removal in patients with benign prostatic hyperplasia (BPH) treated with GreenLight laser photoselective vaporization of the prostate (PVP). MATERIALS AND METHODS: Patients (n=200) with BPH treated with PVP were divided into perfusion (n=100) and control (n=100) groups. For the perfusion group, saline (200 mL or the maximum capacity tolerated) was irrigated into the bladder after standardized external urethral disinfection, and the catheter was removed. Catheter removal was routinely performed in the control group. Perioperative adverse events and clinical outcomes were compared between the groups. RESULTS: Patients in the perfusion group had a shorter waiting time [3 (0-4) vs. 15 (8.75-26) min; P<0.001] and a better satisfaction grade [24 (21.75-26) vs. 23 (20-25); P=0.016] for first urination than those in the control group. The perfusion group exhibited lower anxiety levels regarding first urination than the control group [1 (1-2) vs. 1.5 (1-2), respectively; P=0.012]. Urinalysis revealed that the perfusion group had significantly lower white blood cell (WBC) count than the control group on the day [25.5 (8-37.75) vs. 43.5 (24.0-64.75); P<0.001] and 2 weeks [20.5 (11-27) vs. 31.0 (20-42); P<0.001] after catheter removal. No significant differences in treatment-related adverse events were observed [perfusion (n=15), control (n=20)]. CONCLUSION: Saline perfusion before catheter removal in patients with BPH treated with PVP could shorten the waiting time for first urination, improve patient anxiety and satisfaction and reduce postoperative urinary WBC levels.

Statistical machine learning models for prediction of China's maritime emergency patients in dynamic: ARIMA model, SARIMA model, and dynamic Bayesian network model.

Introduction: Rescuing individuals at sea is a pressing global public health issue, garnering substantial attention from emergency medicine researchers with a focus on improving prevention and control strategies. This study aims to develop a Dynamic Bayesian Networks (DBN) model utilizing maritime emergency incident data and compare its forecasting accuracy to Auto-regressive Integrated Moving Average (ARIMA) and Seasonal Auto-regressive Integrated Moving Average (SARIMA) models. Methods: In this research, we analyzed the count of cases managed by five hospitals in Hainan Province from January 2016 to December 2020 in the context of maritime emergency care. We employed diverse approaches to construct and calibrate ARIMA, SARIMA, and DBN models. These models were subsequently utilized to forecast the number of emergency responders from January 2021 to December 2021. The study indicated that the ARIMA, SARIMA, and DBN models effectively modeled and forecasted Maritime Emergency Medical Service (EMS) patient data, accounting for seasonal variations. The predictive accuracy was evaluated using Mean Absolute Error (MAE), Root Mean Squared Error (RMSE), and Coefficient of Determination (R 2) as performance metrics. Results: In this study, the ARIMA, SARIMA, and DBN models reported RMSE of 5.75, 4.43, and 5.45; MAE of 4.13, 2.81, and 3.85; and R 2 values of 0.21, 0.54, and 0.44, respectively. MAE and RMSE assess the level of difference between the actual and predicted values. A smaller value indicates a more accurate model prediction. R 2 can compare the performance of models across different aspects, with a range of values from 0 to 1. A value closer to 1 signifies better model quality. As errors increase, R 2 moves further from the maximum value. The SARIMA model outperformed the others, demonstrating the lowest RMSE and MAE, alongside the highest R 2, during both modeling and forecasting. Analysis of predicted values and fitting plots reveals that, in most instances, SARIMA's predictions closely align with the actual number of rescues. Thus, SARIMA is superior in both fitting and forecasting, followed by the DBN model, with ARIMA showing the least accurate predictions. Discussion: While the DBN model adeptly captures variable correlations, the SARIMA model excels in forecasting maritime emergency cases. By comparing these models, we glean valuable insights into maritime emergency trends, facilitating the development of effective prevention and control strategies.

Tailoring soy protein/corn zein mixture by limited enzymatic hydrolysis to improve digestibility and functionality.

This study aimed to modify plant protein mixture to improve their functionality and digestibility by limited hydrolysis. Soy protein isolate and corn zein were mixed at the ratio of 5:1 (w/w), followed by limited hydrolysis using papain from 15 to 30 min. The structural characteristics, in vitro digestibility, and functional properties were evaluated. Also, DPPH radical scavenging activity was determined. The results indicated that the molecular weight of different modified samples was largely reduced by limited hydrolysis, and the proportion of random coil was significantly increased. Furthermore, the solubility, foaming, emulsifying and water-holding capacity of hydrolyzed protein mixture were significantly improved, which were close to those of whey protein isolate. In vitro digestibility after 30-min limited hydrolysis was remarkably elevated. In addition, the hydrolyzed protein mixture exhibited a higher antioxidant activity than those of untreated proteins. Overall, limited hydrolysis of protein mixture led to improved digestibility, functionality and antioxidant activity.

Targeting Cholesterol Biosynthesis with Statins Synergizes with AKT Inhibitors in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is responsible for a disproportionate number of breast cancer patient deaths due to extensive molecular heterogeneity, high recurrence rates and lack of targeted therapies. Dysregulation of the phosphoinositide 3-kinase (PI3K)/AKT pathway occurs in approximately 50% of TNBC patients. Here, we performed a genome-wide CRISPR/Cas9 screen with PI3Kα and AKT inhibitors to find targetable synthetic lethalities in TNBC. Cholesterol homeostasis was identified as a collateral vulnerability with AKT inhibition. Disruption of cholesterol homeostasis with pitavastatin synergized with AKT inhibition to induce TNBC cytotoxicity in vitro, in mouse TNBC xenografts and in patient-derived, estrogen receptor (ER)-negative breast cancer organoids. Neither ER-positive breast cancer cell lines nor ER-positive organoids were sensitive to combined AKT inhibitor and pitavastatin. Mechanistically, TNBC cells showed impaired sterol regulatory element-binding protein 2 (SREBP-2) activation in response to single agent or combination treatment with AKT inhibitor and pitavastatin, which was rescued by inhibition of the cholesterol trafficking protein Niemann-Pick C1 (NPC1). NPC1 loss caused lysosomal cholesterol accumulation, decreased endoplasmic reticulum cholesterol levels, and promoted SREBP-2 activation. Taken together, these data identify a TNBC-specific vulnerability to the combination of AKT inhibitors and pitavastatin mediated by dysregulated cholesterol trafficking. These findings support combining AKT inhibitors with pitavastatin as a therapeutic modality in TNBC. .