Osteoclasts recycle via osteomorphs during RANKL-stimulated bone resorption.

Osteoclasts are large multinucleated bone-resorbing cells formed by the fusion of monocyte/macrophage-derived precursors that are thought to undergo apoptosis once resorption is complete. Here, by intravital imaging, we reveal that RANKL-stimulated osteoclasts have an alternative cell fate in which they fission into daughter cells called osteomorphs. Inhibiting RANKL blocked this cellular recycling and resulted in osteomorph accumulation. Single-cell RNA sequencing showed that osteomorphs are transcriptionally distinct from osteoclasts and macrophages and express a number of non-canonical osteoclast genes that are associated with structural and functional bone phenotypes when deleted in mice. Furthermore, genetic variation in human orthologs of osteomorph genes causes monogenic skeletal disorders and associates with bone mineral density, a polygenetic skeletal trait. Thus, osteoclasts recycle via osteomorphs, a cell type involved in the regulation of bone resorption that may be targeted for the treatment of skeletal diseases.

Endoplasmic Reticulum-Targeting Self-Assembly Nanosheets Promote Autophagy and Regulate Immunosuppressive Tumor Microenvironment for Efficient Photodynamic Immunotherapy.

The poor efficiency and low immunogenicity of photodynamic therapy (PDT), and the immunosuppressive tumor microenvironment (ITM) lead to tumor recurrence and metastasis. In this work, TCPP-TER-Zn@RSV nanosheets (TZR NSs) that co-assembled from the endoplasmic reticulum (ER)-targeting photosensitizer TCPP-TER-Zn nanosheets (TZ NSs for short) and the autophagy promoting and indoleamine-(2, 3)-dioxygenase (IDO) inhibitor-like resveratrol (RSV) are fabricated to enhance antitumor PDT. TZR NSs exhibit improved therapeutic efficiency and amplified immunogenic cancer cell death (ICD) by ER targeting PDT and ER autophagy promotion. TZR NSs reversed the ITM with an increase of CD8+ T cells and reduce of immunosuppressive Foxp3 regulatory T cells, which effectively burst antitumor immunity thus clearing residual tumor cells. The ER-targeting TZR NSs developed in this paper presents a simple but valuable reference for high-efficiency tumor photodynamic immunotherapy.

TRPV1 Dysfunction Impairs Gastric Nitrergic Neuromuscular Relaxation in High-Fat Diet-Induced Diabetic Gastroparesis Mice.

Diabetic gastroparesis (DGP) is characterized by delayed gastric emptying of solid food. Nitrergic neuron-mediated fundus relaxation and intragastric peristalsis are pivotal for gastric emptying and are impaired in DGP. Transient receptor potential vanilloid 1 (TRPV1) ion channels are expressed in gastrointestinal vagal afferent nerves and have a potential role in relevant gastrointestinal disorders. In this study, mice with high-fat diet (HFD)-induced type 2 diabetes mellitus (T2DM), associated with gastroparesis, were used to determine the role of TRPV1 in DGP. After feeding with HFD, mice exhibited obesity, hyperglycemia, insulin resistance, and delayed gastric emptying. Cholinergic- and nitrergic neuron-mediated neuromuscular contractions and relaxation were impaired. The antral tone of the DGP mice was attenuated. Interestingly, activating or suppressing TRPV1 facilitated or inhibited gastric fundus relaxation in normal mice. These effects were neutralized by using a nitric oxide synthase (NOS) inhibitor. Activation or suppression of TRPV1 also increased or reduced NO release. TRPV1 was specifically localized with neuronal NOS in the gastric fundus. These data suggest that TRPV1 activation facilitates gastric fundus relaxation by regulating neuronal NOS and promoting NO release. However, these effects and mechanisms disappeared in mice with DGP induced by HFD diet. TRPV1 expression was only marginally decreased in the fundus of DGP mice. TRPV1 dysfunction may be a potential mechanism underlying the dysfunction of DGP gastric nitrergic neuromuscular relaxation.

Accounting for the microbial assembly of each process in wastewater treatment plants (WWTPs): study of four WWTPs receiving similar influent streams.

We evaluated a unique model in which four full-scale wastewater treatment plants (WWTPs) with the same treatment schematic and fed with similar influent wastewater were tracked over an 8-month period to determine whether the community assembly would differ in the activated sludge (AS) and sand filtration (SF) stages. For each WWTP, AS and SF achieved an average of 1-log10 (90%) and <0.02-log10 (5%) reduction of total cells, respectively. Despite the removal of cells, both AS and SF had a higher alpha and beta diversity compared to the influent microbial community. Using the Sloan neutral model, it was observed that AS and SF were individually dominated by different assembly processes. Specifically, microorganisms from influent to AS were predominantly determined by the selective niche process for all WWTPs, while the microbial community in the SF was relatively favored by a stochastic, random migration process, except two WWTPs. AS also contributed more to the final effluent microbial community compared with the SF. Given that each WWTP operates the AS independently and that there is a niche selection process driven mainly by the chemical oxygen demand concentration, operational taxonomic units unique to each of the WWTPs were also identified. The findings from this study indicate that each WWTP has its distinct microbial signature and could be used for source-tracking purposes.IMPORTANCEThis study provided a novel concept that microorganisms follow a niche assembly in the activated sludge (AS) tank and that the AS contributed more than the sand filtration process toward the final microbial signature that is unique to each treatment plant. This observation highlights the importance of understanding the microbial community selected by the AS stage, which could contribute toward source-tracking the effluent from different wastewater treatment plants.

Utilizing radiomics and dosiomics with AI for precision prediction of radiation dermatitis in breast cancer patients.

PURPOSE: This study explores integrating clinical features with radiomic and dosiomic characteristics into AI models to enhance the prediction accuracy of radiation dermatitis (RD) in breast cancer patients undergoing volumetric modulated arc therapy (VMAT). MATERIALS AND METHODS: This study involved a retrospective analysis of 120 breast cancer patients treated with VMAT at Kaohsiung Veterans General Hospital from 2018 to 2023. Patient data included CT images, radiation doses, Dose-Volume Histogram (DVH) data, and clinical information. Using a Treatment Planning System (TPS), we segmented CT images into Regions of Interest (ROIs) to extract radiomic and dosiomic features, focusing on intensity, shape, texture, and dose distribution characteristics. Features significantly associated with the development of RD were identified using ANOVA and LASSO regression (p-value < 0.05). These features were then employed to train and evaluate Logistic Regression (LR) and Random Forest (RF) models, using tenfold cross-validation to ensure robust assessment of model efficacy. RESULTS: In this study, 102 out of 120 VMAT-treated breast cancer patients were included in the detailed analysis. Thirty-two percent of these patients developed Grade 2+ RD. Age and BMI were identified as significant clinical predictors. Through feature selection, we narrowed down the vast pool of radiomic and dosiomic data to 689 features, distributed across 10 feature subsets for model construction. In the LR model, the J subset, comprising DVH, Radiomics, and Dosiomics features, demonstrated the highest predictive performance with an AUC of 0.82. The RF model showed that subset I, which includes clinical, radiomic, and dosiomic features, achieved the best predictive accuracy with an AUC of 0.83. These results emphasize that integrating radiomic and dosiomic features significantly enhances the prediction of Grade 2+ RD. CONCLUSION: Integrating clinical, radiomic, and dosiomic characteristics into AI models significantly improves the prediction of Grade 2+ RD risk in breast cancer patients post-VMAT. The RF model analysis demonstrates that a comprehensive feature set maximizes predictive efficacy, marking a promising step towards utilizing AI in radiation therapy risk assessment and enhancing patient care outcomes.

Adipocyte pyroptosis occurs in omental tumor microenvironment and is associated with chemoresistance of ovarian cancer.

BACKGROUND: Ovarian carcinoma (OC) is a fatal malignancy, with most patients experiencing recurrence and resistance to chemotherapy. In contrast to hematogenous metastasizing tumors, ovarian cancer cells disseminate within the peritoneal cavity, especially the omentum. Previously, we reported omental crown-like structure (CLS) number is associated with poor prognosis of advanced-stage OC. CLS that have pathologic features of a dead or dying adipocyte was surrounded by several macrophages is well known a histologic hallmark for inflammatory adipose tissue. In this study, we attempted to clarify the interaction between metastatic ovarian cancer cells and omental CLS, and to formulate a therapeutic strategy for advanced-stage ovarian cancer. METHODS: A three-cell (including OC cells, adipocytes and macrophages) coculture model was established to mimic the omental tumor microenvironment (TME) of ovarian cancer. Caspase-1 activity, ATP and free fatty acids (FFA) levels were detected by commercial kits. An adipocyte organoid model was established to assess macrophages migration and infiltration. In vitro and in vivo experiments were performed for functional assays and therapeutic effect evaluations. Clinical OC tissue samples were collected for immunochemistry stain and statistics analysis. RESULTS: In three-cell coculture model, OC cells-derived IL-6 and IL-8 could induce the occurrence of pyroptosis in omental adipocytes. The pyroptotic adipocytes release ATP to increase macrophage infiltration, release FFA into TME, uptake by OC cells to increase chemoresistance. From OC tumor samples study, we demonstrated patients with high gasdermin D (GSDMD) expression in omental adipocytes is highly correlated with chemoresistance and poor outcome in advanced-stage OC. In animal model, by pyroptosis inhibitor, DSF, effectively retarded tumor growth and prolonged mice survival. CONCLUSIONS: Omental adipocyte pyroptosis may contribute the chemoresistance in advanced stage OC. Omental adipocytes could release FFA and ATP through the GSDMD-mediate pyroptosis to induce chemoresistance and macrophages infiltration resulting the poor prognosis in advanced-stage OC. Inhibition of adipocyte pyroptosis may be a potential therapeutic modality in advanced-stage OC with omentum metastasis.

Long-term effects of fecal microbiota transplantation on gut microbiota after Helicobacter pylori eradication with bismuth quadruple therapy: A randomized controlled trial.

BACKGROUND: Eradicating Helicobacter pylori infection by bismuth quadruple therapy (BQT) is effective. However, the effect of BQT and subsequent fecal microbiota transplant (FMT) on the gut microbiota is less known. MATERIALS AND METHODS: This prospective randomized controlled trial was conducted at a tertiary hospital in China from January 2019 to October 2020, with the primary endpoints the effect of BQT on the gut microbiota and the effect of FMT on the gut microbiota after bismuth quadruple therapy eradication therapy. A 14-day BQT with amoxicillin and clarithromycin was administered to H. pylori-positive subjects, and after eradication therapy, patients received a one-time FMT or placebo treatment. We then collected stool samples to assess the effects of 14-day BQT and FMT on the gut microbiota. 16 s rDNA and metagenomic sequencing were used to analyze the structure and function of intestinal flora. We also used Gastrointestinal Symptom Rating Scale (GSRS) to evaluate gastrointestinal symptom during treatment. RESULTS: A total of 30 patients were recruited and 15 were assigned to either FMT or placebo groups. After eradication therapy, alpha-diversity was decreased in both groups. At the phylum level, the abundance of Bacteroidetes and Firmicutes decreased, while Proteobacteria increased. At the genus level, the abundance of beneficial bacteria decreased, while pathogenic bacteria increased. Eradication therapy reduced some resistance genes abundance while increased the resistance genes abundance linked to Escherichia coli. While they all returned to baseline by Week 10. Besides, the difference was observed in Week 10 by the diarrhea score between two groups. Compared to Week 2, the GSRS total score and diarrhea score decreased in Week 3 only in FMT group. CONCLUSIONS: The balance of intestinal flora in patients can be considerably impacted by BQT in the short term, but it has reverted back to baseline by Week 10. FMT can alleviate gastrointestinal symptoms even if there was no evidence it promoted restoration of intestinal flora.

Predicting Anaerobic Membrane Bioreactor Performance Using Flow-Cytometry-Derived High and Low Nucleic Acid Content Cells.

Having a tool to monitor the microbial abundances rapidly and to utilize the data to predict the reactor performance would facilitate the operation of an anaerobic membrane bioreactor (AnMBR). This study aims to achieve the aforementioned scenario by developing a linear regression model that incorporates a time-lagging mode. The model uses low nucleic acid (LNA) cell numbers and the ratio of high nucleic acid (HNA) to LNA cells as an input data set. First, the model was trained using data sets obtained from a 35 L pilot-scale AnMBR. The model was able to predict the chemical oxygen demand (COD) removal efficiency and methane production 3.5 days in advance. Subsequent validation of the model using flow cytometry (FCM)-derived data (at time t - 3.5 days) obtained from another biologically independent reactor did not exhibit any substantial difference between predicted and actual measurements of reactor performance at time t. Further cell sorting, 16S rRNA gene sequencing, and correlation analysis partly attributed this accurate prediction to HNA genera (e.g., Anaerovibrio and unclassified Bacteroidales) and LNA genera (e.g., Achromobacter, Ochrobactrum, and unclassified Anaerolineae). In summary, our findings suggest that HNA and LNA cell routine enumeration, along with the trained model, can derive a fast approach to predict the AnMBR performance.

Risk of diabetes and hypertension in a population with alcohol use disorders.

BACKGROUND: A population-based follow-up study assessing the risk of developing hypertension and diabetes associated with alcohol use disorder (AUD) is crucial. We investigated this relationship by using insurance claims data from Taiwan. METHODS: From the claims data, an AUD cohort (N = 60,590) diagnosed between 2000 and 2006 and a non-AUD comparison cohort (N = 60,590) without the diagnosis of hypertension or diabetes at baseline were established and matched by propensity scores estimated by baseline demographic status and the Charlson comorbidity index (CCI). We assessed the incidence rates of hypertension and/or diabetes at the end of 2016 and used Cox's method to estimate the related hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Relative to the comparison cohort, the AUD cohort had an approximately 1.70-fold higher incidence of hypertension (35.1 vs. 20.7 per 1,000 person-years), with an adjusted HR (aHR) of 1.72 (95% CI: 1.68-1.76), 2.16-fold higher incidence of diabetes (20.2 vs. 9.36 per 1,000 person-years), with an aHR of 2.18 (95% CI: 2.11-2.24), and 1.91-fold higher incidence of both diabetes and hypertension (10.3 vs. 5.38 per 1,000 person-years) with an aHR of 2.02 (95% CI: 1.94-2.10). The incidence rates of all outcomes were greater in men than in women, whereas the HRs were greater for AUD in women than for AUD in men relative to the respective comparison patients. The risk increased further for subjects with CCI ≥ 1, which was higher in the AUD cohort. CONCLUSIONS: The increased risk of developing diabetes and hypertension in patients with AUD, especially the differences noted according to gender, indicates that clinicians should address potential comorbidities in these patients.

A single all-out bout of 30-s sprint-cycle performed on 5 consecutive days per week over 6 weeks does not enhance cardiovascular fitness, maximal strength, and clinical health markers in physically active young adults.

BACKGROUND: This study examined the effects of a single all-out bout of 30-s sprint-cycle performed daily for 5 consecutive days per week for 6 weeks, on aerobic fitness, muscle strength and metabolic-health markers in physically active young males and females. METHODS: Healthy, physically active 20-28 year olds, were randomly assigned to either experimental (EXP, N = 11) or non-training control (CON, N = 8) group. With supervision, the EXP group performed one bout of 30-s sprint-cycle daily, Mondays to Fridays over 6 weeks, while CON group continued with their usual lifestyle. The followings were measured at pre- and post-intervention: maximal aerobic power, peak torque of knee extensors and flexors at velocities 30° s-1 and 300° s-1, resting heart rate, resting blood pressure, body fat percentage, fasting lipid profile, fasting blood glucose, and fasting insulin levels. RESULTS: There were no significant improvements in the EXP group for all the measured variables (all P > 0.05); except for significant interaction effects in peak torque of knee extensors at 30° s-1 (P = 0.044) and low-density lipoprotein-cholesterol (P = 0.046). Post hoc test indicate that CON group showed decline in their low-density lipo-proteins levels (P = 0.024). CONCLUSION: Six weeks of one all-out bout of 30-s sprint-cycle per day, for 5 consecutive days per week, was ineffective in improving cardiovascular fitness, maximal strength, and most health markers in physically active young adults. The present results when combined with the previous literature suggest that there is a possibility of a minimum threshold for a number of sprint-cycle bouts needed to be performed before any form of cardio-metabolic-health benefit is accrued.

UV and bacteriophages as a chemical-free approach for cleaning membranes from anaerobic bioreactors.

Anaerobic membrane bioreactor (AnMBR) for wastewater treatment has attracted much interest due to its efficacy in providing high-quality effluent with minimal energy costs. However, membrane biofouling represents the main bottleneck for AnMBR because it diminishes flux and necessitates frequent replacement of membranes. In this study, we assessed the feasibility of combining bacteriophages and UV-C irradiation to provide a chemical-free approach to remove biofoulants on the membrane. The combination of bacteriophage and UV-C resulted in better log cells removal and ca. 2× higher extracellular polymeric substance (EPS) concentration reduction in mature biofoulants compared to either UV-C or bacteriophage alone. The cleaning mechanism behind this combined approach is by 1) reducing the relative abundance of Acinetobacter spp. and selected bacteria (e.g., Paludibacter, Pseudomonas, Cloacibacterium, and gram-positive Firmicutes) associated with the membrane biofilm and 2) forming cavities in the biofilm to maintain water flux through the membrane. When the combined treatment was further compared with the common chemical cleaning procedure, a similar reduction on the cell numbers was observed (1.4 log). However, the combined treatment was less effective in removing EPS compared with chemical cleaning. These results suggest that the combination of UV-C and bacteriophage have an additive effect in biofouling reduction, representing a potential chemical-free method to remove reversible biofoulants on membrane fitted to an AnMBR.

Toxicokinetics and bioavailability of indoxacarb enantiomers and their new metabolites in rats.

Indoxacarb is a chiral insecticide that consists of two enantiomers, S-(+)-indoxacarb and R-(-)-indoxacarb, of which only S-(+)-indoxacarb has insecticidal activity. Previous enantioselective toxicology studies of indoxacarb focused mostly on simple environmental model organisms. The lack of a toxicology evaluation of indoxacarb conducted in a mammalian system could mean that the extent of the potential health risk posed by the insecticide to humans is not adequately known. In this study, we reported on a new pair of enantiomers, S-IN-RM294 and R-IN-RM294, derived from the metabolic breakdown of S-(+)-indoxacarb and R-(-)-indoxacarb, respectively, in rats. The toxicokinetics of S-(+)-indoxacarb, R-(-)-indoxacarb, S-IN-RM294, and R-IN-RM294 in rats were evaluated to provide a more comprehensive risk assessment of these molecules. The bioavailability and excretion rates of both S-(+)-indoxacarb and R-(-)-indoxacarb were relatively low, which may be due to their faster metabolism and accumulation in the tissues. In addition, there were significant differences in the metabolism and distribution between the two indoxacarb enantiomers and their metabolites in vivo. S-(+)-Indoxacarb was found to be more easily metabolized in the blood compared with R-(-)-indoxacarb, as shown by the differences in pharmacokinetic parameters between oral and intravenous administration. Analysis of their tissue distribution showed that S-(+)-indoxacarb was less likely to accumulate in most tissues. The results obtained for the two metabolites were consistent with those of the two parent compounds. S-IN-RM294 was more readily cleared from the blood and less likely to accumulate in the tissues compared with R-IN-RM294. Therefore, whether from the perspective of insecticidal activity or from the perspective of mammalian and environmental friendliness, the application of optically pure S-(+)-indoxacarb in agriculture may be a more efficient and safer strategy.

5,7,3',4'-Tetramethoxyflavone suppresses TGF-ß1-induced activation of murine fibroblasts in vitro and ameliorates bleomycin-induced pulmonary fibrosis in mice.

OBJECTIVE: This study aimed to investigate the use of 5,7,3',4'-tetramethoxyflavone (TMF) to treat pulmonary fibrosis (PF), a chronic and fatal lung disease. In vitro and in vivo models were used to examine the impact of TMF on PF. METHODS: NIH-3T3 (Mouse Embryonic Fibroblast) were exposed to transforming growth factor­ß1 (TGF-ß1) and treated with or without TMF. Cell growth was assessed using the MTT method, and cell migration was evaluated with the scratch wound assay. Protein and messenger ribonucleic acid (mRNA) levels of extracellular matrix (ECM) genes were analyzed by western blotting and quantitative reverse transcription-polymerase chain reaction (RT-PCR), respectively. Downstream molecules affected by TGF-ß1 were examined by western blotting. In vivo, mice with bleomycin-induced PF were treated with TMF, and lung tissues were analyzed with staining techniques. RESULTS: The in vitro results showed that TMF had no significant impact on cell growth or migration. However, it effectively inhibited myofibroblast activation and ECM production induced by TGF-ß1 in NIH-3T3 cells. This inhibition was achieved by suppressing various signaling pathways, including Smad, mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase/AKT (PI3K/AKT), and WNT/ß-catenin. The in vivo experiments demonstrated the therapeutic potential of TMF in reducing PF induced by bleomycin in mice, and there was no significant liver or kidney toxicity observed. CONCLUSION: These findings suggest that TMF has the potential to effectively inhibit myofibroblast activation and could be a promising treatment for PF. TMF achieves this inhibitory effect by targeting TGF-ß1/Smad and non-Smad pathways.

Rhodiola and Salidroside Attenuate Oxidative Stress-Triggered H9c2 Cardiomyoblast Apoptosis Through IGF1R-Induced ERK1/2 Activation.

Oxidative stress is a pivotal factor in the pathogenesis of various cardiovascular diseases. Rhodiola, a traditional Chinese medicine, is recognized for its potent antioxidant properties. Salidroside, a phenylpropanoid glycoside derived from Rhodiola rosea, has shown remarkable antioxidant capabilities. This study aimed to elucidate the potential protective mechanisms of Rhodiola and salidroside against H2O2-induced cardiac apoptosis in H9c2 cardiomyoblast cells. H9c2 cells were exposed to H2O2 for 4 h, and subsequently treated with Rhodiola or salidroside for 24 h. Cell viability and apoptotic pathways were assessed. The involvement of insulin-like growth factor 1 receptor (IGF1R) and the activation of extracellular regulated protein kinases 1/2 (ERK1/2) were investigated. H2O2 (100 µM) exposure significantly induced cardiac apoptosis in H9c2 cells. However, treatment with Rhodiola (12.5, 25, and 50 µg/mL) and salidroside (0.1, 1, and 10 nM) effectively attenuated H2O2-induced cytotoxicity and apoptosis. This protective effect was associated with IGF1R-activated phosphorylation of ERK1/2, leading to the inhibition of Fas-dependent proteins, HIF-1α, Bax, and Bak expression in H9c2 cells. The images from hematoxylin and eosin staining and immunofluorescence assays also revealed the protective effects of Rhodiola and salidroside in H9c2 cells against oxidative damage. Our findings suggest that Rhodiola and salidroside possess antioxidative properties that mitigate H2O2-induced apoptosis in H9c2 cells. The protective mechanisms involve the activation of IGF1R and subsequent phosphorylation of ERK1/2. These results propose Rhodiola and salidroside as potential therapeutic agents for cardiomyocyte cytotoxicity and apoptosis induced by oxidative stress in heart diseases. Future studies may explore their clinical applications in cardiac health.

Platycodi radix aqueous extract salvages doxorubicin-induced senescence by mitochondrial reactive oxygen species reduction in umbilical cord matrix stem cells.

Platycodi radix is a widely used herbal medicine that contains numerous phytochemicals beneficial to health. The health and biological benefits of P. radix have been found across various diseases. The utilization of umbilical cord stromal stem cells, derived from Wharton's jelly of the human umbilical cord, has emerged as a promising approach for treating degenerative diseases. Nevertheless, growing evidence indicates that the function of stem cells declines with age, thereby limiting their regenerative capacity. The primary objective in this study is to investigate the beneficial effects of P. radix in senescent stem cells. We conducted experiments to showcase that diminished levels of Lamin B1 and Sox-2, along with an elevation in p21, which serve as indicative markers for the senescent stem cells. Our findings revealed the loss of Lamin B1 and Sox-2, coupled with an increase in p21, in umbilical cord stromal stem cells subjected to a low-dose (0.1 µM) doxorubicin (Dox) stimulation. However, P. radix restored the Dox-damage in the umbilical cord stromal stem cells. P. radix reversed the senescent conditions when the umbilical cord stromal stem cells exposed to Dox-induced reactive oxygen species (ROS) and mitochondrial membrane potential are significantly changed. In Dox-challenged aged umbilical cord stromal stem cells, P. radix reduced senescence, increased longevity, prevented mitochondrial dysfunction and ROS and protected against senescence-associated apoptosis. This study suggests that P. radix might be as a therapeutic and rescue agent for the aging effect in stem cells. Inhibition of cell death, mitochondrial dysfunction and aging-associated ROS with P. radix provides additional insights into the underlying molecular mechanisms.

Understanding Healthcare Providers' Care for Patients with Medications Treating Opioid Use Disorder in the Emergency Department: A Scoping Review.

BACKGROUND: There is limited research exploring the changing clinical practices among healthcare providers (HPs) care for patients with Emergency Department (ED)-initiated Medication for Opioid Use Disorder (MOUD). METHODS: This scoping review followed the methodological framework of Arksey and O'Malley to map relevant evidence and synthesize the findings. We searched PubMed, EMBASE, CINAHL, Web of Science, and Scopus for related studies from inception through October 12, 2022. Following the application of inclusion and exclusion criteria, 16 studies were included. Subsequently, they were charted and analyzed thematically based on ecological systems theory. RESULTS: The main determinants in the four ecological systems were generated as follows: (1) microsystem: willingness and attitude, professional competence, readiness, and preference; (2) mesosystem: ED clinical practices, departmental factors; (3) exosystem: multidisciplinary approaches, discharge planning, and (4) macrosystem: stigma, health insurance, policy. The findings have implications for HPs and researchers, as insufficient adoption, implementation, and retention of MOUD in the ED affect clinical practices. CONCLUSIONS: Across the four ecological systems, ED-initiated MOUD is shaped by multifaceted determinants. The microsystem underscores pivotal patient-HP trust dynamics, while the mesosystem emphasizes interdepartmental synergies. Exosystemically, resource allocation and standardized training remain paramount. The macrosystem reveals profound effects of stigma, insurance disparities, and evolving policies on treatment access and efficacy. Addressing these interconnected barriers is crucial for optimizing patient outcomes in the context of MOUD.

The effects of neurofeedback training for children with cerebral palsy and co-occurring attention deficits: A pilot study.

BACKGROUND: Limited research exists regarding the effectiveness of electroencephalogram (EEG) neurofeedback training for children with cerebral palsy (CP) and co-occurring attention deficits (ADs), despite the increasing prevalence of these dual conditions. This study aimed to fill this gap by examining the impact of neurofeedback training on the attention levels of children with CP and AD. METHODS: Nineteen children with both CP and co-occurring ADs were randomly assigned to either a neurofeedback or control group. The neurofeedback group received 20 sessions of training, lasting approximately 1 h per day, twice a week. Theta/beta ratios of the quantitative electroencephalography (QEEG) recordings were measured pre-training and post-training in the resting state. The Continuous Performance Test (CPT), the Test of Visual Perceptual Skills-3rd Version (TVPS-3) and the Conners' Parent Rating Scale (CPRS) were measured at pre- and post-training. RESULTS: The neurofeedback group showed both decreased theta/beta ratios compared with control group (p = 0.04) at post-training and a within-group improvement during training (p = 0.02). Additionally, the neurofeedback group had a trend of decreased omission rates of the CPT (p = 0.08) and the visual sequential memory and the visual closure subscores in the TVPS-3, compared with the control group (p = 0.02 and p = 0.01, respectively). CONCLUSIONS: The results suggested that children with CP and co-occurring AD may benefit from neurofeedback training in their attention level. Further research is needed to explore long-term effects and expand its application in this population.

Tissue Inhibitor of Metalloproteinase 3: Unravelling Its Biological Function and Significance in Oncology.

Tissue inhibitor of metalloproteinases-3 (TIMP3) is vital in regulating several biological processes. TIMP3 exerts antitumour effects via matrix metalloproteinase (MMP)-dependent and MMP-independent pathways. Due to promoter methylation and miRNA binding, TIMP3 expression has been observed to decrease in various cancers. Consequently, the migration and invasion of cancer cells increases. Conflicting results have reported that expression levels of TIMP3 in primary and advanced cancers are higher than those in healthy tissues. Therefore, the role of TIMP3 in cancer biology and progression needs to be elucidated. This review provides an overview of TIMP3, from its biological function to its effects on various cancers. Moreover, gynaecological cancers are discussed in detail. TIMP3 has been associated with cervical adenocarcinoma as well as cancer development in serous ovarian cancer and breast cancer metastasis. However, the relationship between TIMP3 and endometrial cancers remains unclear. TIMP3 may be a useful biomarker for gynaecological cancers and is a potential target for future cancer therapy.

Production of Bioactive Porcine Lactoferrin through a Novel Glucose-Inducible Expression System in Pichia pastoris: Unveiling Antimicrobial and Anticancer Functionalities.

Lactoferrin (LF) stands as one of the extensively investigated iron-binding glycoproteins within milk, exhibiting diverse biological functionalities. The global demand for LF has experienced consistent growth. Biotechnological strategies aimed at enhancing LF productivity through microbial expression systems offer substantial cost-effective advantages and exhibit fewer constraints compared to traditional animal bioreactor technologies. This study devised a novel recombinant plasmid, wherein the AOX1 promoter was replaced with a glucose-inducible G1 promoter (PG1) to govern the expression of recombinant porcine LF (rpLF) in Pichia pastoris GS115. High-copy-number PG1-rpLF yeast clones were meticulously selected, and subsequent induction with 0.05 g/L glucose demonstrated robust secretion of rpLF. Scaling up production transpired in a 5 L fermenter, yielding an estimated rpLF productivity of approximately 2.8 g/L by the conclusion of glycerol-fed fermentation. A three-step purification process involving tangential-flow ultrafiltration yielded approximately 6.55 g of rpLF crude (approximately 85% purity). Notably, exceptional purity of rpLF was achieved through sequential heparin and size-exclusion column purification. Comparatively, the present glucose-inducible system outperformed our previous methanol-induced system, which yielded a level of 87 mg/L of extracellular rpLF secretion. Furthermore, yeast-produced rpLF demonstrated affinity for ferric ions (Fe3+) and exhibited growth inhibition against various pathogenic microbes (E. coli, S. aureus, and C. albicans) and human cancer cells (A549, MDA-MB-231, and Hep3B), similar to commercial bovine LF (bLF). Intriguingly, the hydrolysate of rpLF (rpLFH) manifested heightened antimicrobial and anticancer effects compared to its intact form. In conclusion, this study presents an efficient glucose-inducible yeast expression system for large-scale production and purification of active rpLF protein with the potential for veterinary or medical applications.