Therapy-related myeloid neoplasms following curative treatment of acute promyelocytic leukemia: incidence, correlation with therapeutic regimen, and future directions.

All-trans retinoic acid (ATRA) and arsenic trioxide (ATO) have revolutionized the treatment of acute promyelocytic leukemia (APL), offering a cure rate of > 80%. Along with improved survival, the long-term consequences of anti-APL therapy are becoming increasingly apparent, including potential therapy-related myeloid neoplasms (t-MNs). T-MNs are well known to arise after cytotoxic chemotherapy, but the leukemogenic potential of regimens utilizing only ATRA/ATO is not well established. The objective of this study is to examine the incidence, long-term risk, and clinicopathologic features of t-MNs arising after anti-APL therapy and how they correlates with the therapeutic regimen employed. We retrospectively collected treated APL patients between 01/2001 and 02/2021, categorized them into ATRA/ATO + chemo and ATRA/ATO groups based on the regimen used, and evaluated for the development of t-MN. A total of 110 APL patients were identified, including 67 (61%) treated with ATRA/ATO + chemo and 43 (39%) treated with ATRA/ATO only. Overall, 4/110 (3.6%) patients developed t-MNs, with all four emerging in the ATRA/ATO + chemo group. Ultimately, the incidence of t-MN in ATRA/ATO + chemo group was significantly higher compared with ATRA/ATO only group(5.97% vs. 0.0%, respectively; p = 0.0289). Our data spanning over two decades suggests that conventional chemotherapy for APL is associated with a small but significant risk of t-MN, whereas ATR/ATO does not carry this risk. This takes on new significance, considering several recent and ongoing trials have shown that a chemotherapy-free approach might become feasible for all risk APL types in the near future. Consequently, the omission of leukemogenic and arguably unnecessary chemotherapy from APL regimens may reduce the incidence of t-MNs in long-term survivors without sacrificing their cure rates.

Delta Immature Platelet Fraction Is Associated With Mortality in Bacteremia Patients.

OBJECTIVES: Immature platelet fraction (IPF) for differentiating bacteremia has been explored, whereas its prognostic correlation remains uncertain. This study aims to confirm the predictive capability of IPF for bacteremia and investigate its association with prognosis. METHODS: Patients with complete blood count (CBC) on the blood culture day (D1) and the preceding day (D0) were retrospectively recruited and categorized into bacteremia and nonbacteremia groups. Immature platelet (IP) analysis, alongside CBC, was conducted. Delta IPF, defined by the absolute values of D1 minus D0 results was calculated. The ability to distinguish bacteremia from nonbacteremia patients, and the correlation with mortality were analyzed. RESULTS: From February to December 2020, a total of 150 patients were enrolled, with 75 having bacteremia. The specificity for delta IPF ≥3.4% to predict bacteremia was 97.3% (95% confidence interval [CI]: 90.7-99.7). When delta IPF ≥3.4% combined with procalcitonin ≥0.5 (ng/mL), the sensitivity was 90.5% (95% CI: 69.6%-98.8%). Within the bacteremia group, delta IPF and the proportion of patients with delta IPF ≥1.5% were significantly higher in nonsurvival, while delta platelet levels did not. Furthermore, delta IPF ≥1.5% was independently associated with 30-day mortality (adjusted odds ratio: 3.88, 95% CI: 1.2%-11.4%; p = 0.020). The 30-day survival curve demonstrated a significant difference between patients with delta IPF ≥1.5% and those without (p < 0.001). CONCLUSIONS: Delta IPF correlates with mortality in bacteremia patients. Our findings suggest IPF not only helps detect bacteremia but also predicts prognosis in the early stage.

"Accelerated" chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL): unraveling the biological gray zone of CLL/SLL in the era of novel therapies.

Accelerated chronic lymphocytic leukemia/small lymphocytic lymphoma (A-CLL/SLL) is a histologically aggressive subtype of CLL/SLL that lies in between conventional CLL/SLL (C-CLL/SLL) and Richter transformation (RT) on the biological spectrum. Although the histologic criteria for A-CLL/SLL were defined 14 years ago, the clinical and genetic characteristics and survival outcomes of these patients have yet to be studied in the era of novel therapies. We retrospectively analyzed the clinicopathologic, genetic, and survival characteristics of 34 patients with confirmed tissue diagnosis of A-CLL/SLL and compared them with 120 patients with C-CLL/SLL. Patients with A-CLL/SLL had significantly higher frequencies of B-symptoms, anemia and thrombocytopenia, splenomegaly, higher LDH, and more advanced Rai stages. A-CLL/SLL showed a significantly higher frequency of TP53 mutations (55.0% vs. 11.5%;p < 0.0001) and deletions (38.2% vs. 8.3%;p < 0.0001), lower isolated del(13q) (5.8% vs. 27.5%;p < 0.0001), and increased incidence of RT (11.76% vs. 0.83%;p = 0.0025). The overall survival of patients with A-CLL/SLL was significantly lower than C-CLL/SLL (median survival: 6.17 years vs. not reached; 2 and 5-year survival rates: 75.5% vs. 94.7% and 53.3% vs. 93.7%, respectively; p < 0.0001); however, novel agents have improved the outcomes dramatically compared to the previously published data in the pre-BTKi era. Our results support the categorization of A-CLL/SLL as a distinct biologically aggressive subtype of CLL/SLL and highlight the need to revise the diagnostic criteria utilizing a multifaceted approach that integrates the overall pathobiological profile of the disease, in addition to the histology.

Short-term usage of proton pump inhibitors during admission was associated with increased risk of rehospitalization in critically ill patients with myocardial infarction: a cohort study.

PURPOSE: Previous studies showed that long-term use of proton pump inhibitors (PPIs) was associated with cardiovascular events. However, the impact of short-term PPI exposure on intensive care unit (ICU) patients with myocardial infarction (MI) remains largely unknown. This study aims to determine the precise correlation between short-term PPI usage during hospitalization and prognostic outcomes of ICU-admitted MI patients using Medical Information Mart for Intensive Care IV database (MIMIC-IV). METHODS: Propensity score matching (PSM) was applied to adjust confounding factors. The primary study outcome was rehospitalization with mortality and length of stay as secondary outcomes. Binary logistic, multivariable Cox, and linear regression analyses were employed to estimate the impact of short-term PPI exposure on ICU-admitted MI patients. RESULTS: A total of 7249 patients were included, involving 3628 PPI users and 3621 non-PPI users. After PSM, 2687 pairs of patients were matched. The results demonstrated a significant association between PPI exposure and increased risk of rehospitalization for MI in both univariate and multivariate [odds ratio (OR) = 1.157, 95% confidence interval (CI) 1.020-1.313] analyses through logistic regression after PSM. Furthermore, this risk was also observed in patients using PPIs > 7 days, despite decreased risk of all-cause mortality among these patients. It was also found that pantoprazole increased the risk of rehospitalization, whereas omeprazole did not. CONCLUSION: Short-term PPI usage during hospitalization was still associated with higher risk of rehospitalization for MI in ICU-admitted MI patients. Furthermore, omeprazole might be superior to pantoprazole regarding the risk of rehospitalization in ICU-admitted MI patients.

Astrocytes in the Ventral Hippocampus Bidirectionally Regulate Innate and Stress-Induced Anxiety-Like Behaviors in Male Mice.

The mechanisms of anxiety disorders, the most common mental illness, remain incompletely characterized. The ventral hippocampus (vHPC) is critical for the expression of anxiety. However, current studies primarily focus on vHPC neurons, leaving the role for vHPC astrocytes in anxiety largely unexplored. Here, genetically encoded Ca2+ indicator GCaMP6m and in vivo fiber photometry calcium imaging are used to label vHPC astrocytes and monitor their activity, respectively, genetic and chemogenetic approaches to inhibit and activate vHPC astrocytes, respectively, patch-clamp recordings to measure glutamate currents, and behavioral assays to assess anxiety-like behaviors. It is found that vHPC astrocytic activity is increased in anxiogenic environments and by 3-d subacute restraint stress (SRS), a well-validated mouse model of anxiety disorders. Genetic inhibition of vHPC astrocytes exerts anxiolytic effects on both innate and SRS-induced anxiety-related behaviors, whereas hM3Dq-mediated chemogenetic or SRS-induced activation of vHPC astrocytes enhances anxiety-like behaviors, which are reversed by intra-vHPC application of the ionotropic glutamate N-methyl-d-aspartate receptor antagonists. Furthermore, intra-vHPC or systemic application of the N-methyl-d-aspartate receptor antagonist memantine, a U.S. FDA-approved drug for Alzheimer's disease, fully rescues SRS-induced anxiety-like behaviors. The findings highlight vHPC astrocytes as critical regulators of stress and anxiety and as potential therapeutic targets for anxiety and anxiety-related disorders.

Rbm24/Notch1 signaling regulates adult neurogenesis in the subventricular zone and mediates Parkinson-associated olfactory dysfunction.

Rationale: Adult neurogenesis in the subventricular zone (SVZ) is essential for maintaining neural homeostasis, and its dysregulation contributes to anosmia and delayed tissue healing in neurological disorders, such as Parkinson's disease (PD). Despite intricate regulatory networks identified in SVZ neurogenesis, the molecular mechanisms dynamically maintaining neural stem/progenitor cells (NSPCs) in response to physiological and pathological stimuli remain incompletely elucidated. Methods: We generated an RNA binding motif protein 24 (Rbm24) knockout model to investigate its impact on adult neurogenesis in the SVZ, employing immunofluorescence, immunoblot, electrophysiology, RNA-sequencing, and in vitro experiments. Further investigations utilized a PD mouse model, along with genetic and pharmacological manipulations, to elucidate Rbm24 involvement in PD pathology. Results: Rbm24, a multifaceted post-transcriptional regulator of cellular homeostasis, exhibited broad expression in the SVZ from development to aging. Deletion of Rbm24 significantly impaired NSPC proliferation in the adult SVZ, ultimately resulting in collapsed neurogenesis in the olfactory bulb. Notably, Rbm24 played a specific role in maintaining Notch1 mRNA stability in adult NSPCs. The Rbm24/Notch1 signaling axis was significantly downregulated in the SVZ of PD mice. Remarkably, overexpression of Rbm24 rescued disruption of adult neurogenesis and olfactory dysfunction in PD mice, and these effects were hindered by DAPT, a potent inhibitor of Notch1. Conclusions: Our findings highlight the critical role of the Rbm24/Notch1 signaling axis in regulating adult SVZ neurogenesis under physiological and pathological circumstances. This provides valuable insights into the dynamic regulation of NSPC homeostasis and offers a potential targeted intervention for PD and related neurological disorders.

Association between parental well-being and preschooler stress measured as hair cortisol concentration: A prospective cohort study.

Hair cortisol concentration (HCC) is a valuable biomarker for evaluating chronic stress in preschoolers. However, few studies have explored early life HCC and its associated factors. This prospective cohort study analysed the HCC in children aged 6-48 months and its associations with parental HCC as well as positive and negative parental mental health outcomes. We used data from the ongoing Longitudinal Examination Across Prenatal and Postpartum Health in Taiwan (LEAPP-HIT) project, conducted in Taipei between 2020 and 2024. Hair samples were collected from both parents and children in 177 families (91 samples obtained during pregnancy and 86 during the postpartum period). The parents also completed self-reported questionnaires. Multiple linear regression was conducted to analyse the data. We observed a significant positive correlation between parents' and preschoolers' HCC. Furthermore, maternal depression (adjusted beta coefficient [aß] = 0.09, 95% confidence interval [CI] = 0.02, 0.16) and perceived stress (aß = 0.15, 95% CI = 0.02, 0.26) were positively associated with preschoolers' HCC. By contrast, higher maternal eudaimonia was associated with lower HCC in preschoolers (aß = -0.11, 95% CI = -0.20, -0.01). For parents, maternal depression, anxiety, and perceived stress were independently associated with an increased HCC during the postnatal period, whereas maternal eudaimonia was negatively associated with HCC. Our results indicate that both mothers and fathers affect children's responses to stress. Assessment of cortisol stress hormone concentrations through hair samples can be a key means of detecting preschoolers' stress levels and enabling early intervention.

Multiple-Dose Pharmacokinetics and Safety of Mitragynine, the Major Alkaloid of Kratom, in Rats.

This study reports the steady-state pharmacokinetic parameters for mitragynine and characterizes its elimination in male and female rats. Four male and female rats were dosed q12h with 40 mg/kg, and orally administered mitragynine for 5 and 6 days, respectively. Using a validated ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method, the plasma concentrations of mitragynine, its metabolites (7-hydroxymitragynine, 9-hydroxycorynantheidine, and mitragynine acid), and a non-CYP oxidation product (3-dehydromitragynine) were determined at various time points. Sex differences in pharmacokinetics were observed, with females demonstrating significantly higher systemic exposure of mitragynine than males. The mitragynine area under the curve normalized by the dose interval (AUC/τ) was 6741.6 ± 869.5 h*ng/mL in female rats and 1808.9 ± 191.3 h*ng/mL in males (p < 0.05). Both sexes produced similar metabolite profiles; the major metabolites were mitragynine acid and 9-hydroxycorynantheidine. 7-Hydroxymitragynine was a minor metabolite. However, higher exposure (AUCs) and the maximum plasma concentrations (C max) of active metabolites, 7-hydroxymitragynine and 9-hydroxycorynantheidine, were observed in female rats and exhibited substantial sex differences. Renal clearance of mitragynine (CLr) was low (0.64 ± 0.3 mL/h in males and 0.98 ± 0.4 mL/h in females), and unchanged mitragynine accounted for <1% of the dose excreted in feces (both sexes). The clinical chemistry, complete blood count, and hematological test results reported no abnormal hematological findings after multiple dosing in either sex.

PAFerroptosis Combined with Metabolic Disturbance of Mito by p52-ZER6 for Enhanced Cancer Immunotherapy induced by Nano-Bacilliform-Enzyme.

The confused gene expressions and molecular mechanisms for mitochondrial dysfunction of traditional nanoenzymes is a challenge for tumor therapy. Herein, a nano-bacilliform-enzyme obtains the ability to inhibit p52-ZER6 signal pathway, regulate the genes related to mitochondrial metabolism, and possess the GOx/CAT/POD-like property. NBE acquires catalytic activity from the electronic energy transition. The tannin of NBE as a mitochondrial (Mito)-targeting guide overloads MitoROS, and then metabolic disorder and lipid peroxidation of Mito membrane occurs, thus leading to a novel death pathway called PAFerroptosis (pyroptosis, apoptosis, and Ferroptosis). Simultaneously, in order to refrain from mitophagy, hydroxychloroquine is mixed with NBE to form a combo with strength pyroptosis. As a result, NBE/combo improves the PAFerroptosis obviously by activation of CD8+T cells and inactivation of MDSC cells, up-regulating expression of caspase-3 signal pathway, intercepting DHODH pathway to arrive excellent antitumor effect (93%). Therefore, this study establishes a rational nanoenzyme for mitochondrial dysfunction without mitophagy for effective antitumor therapy.

A STAT3 Degrader Demonstrates Pre-clinical Efficacy in Venetoclax resistant Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is an aggressive hematologic malignancy that continues to have poor prognosis despite recent therapeutic advances. Venetoclax (Ven), a BCL2-inhibitor has shown a high response rate in AML; however, relapse is invariable due to mitochondrial dysregulation that includes upregulation of the antiapoptotic protein MCL1, a central mechanism of Ven resistance (Ven-res). We have previously demonstrated that the transcription factor STAT3 is upregulated in AML hematopoietic stem and progenitor cells (HSPCs) and can be effectively targeted to induce apoptosis of these aberrant cells. We now show that overexpression of STAT3 alone is sufficient to initiate a strong AML phenotype in a transgenic murine model. Phospho-proteomic data from Ven treated AML patients show a strong correlation of high total STAT3 and phospho-STAT3 [both p-STAT3(Y705) and p-STAT3(S727)] expression with worse survival and reduced remission duration. Additionally, significant upregulation of STAT3 was observed in Ven-res cell lines, in vivo models and primary patient samples. A novel and specific degrader of STAT3 demonstrated targeted reduction of total STAT3 and resulting inhibition of its active p-STAT3(Y705) and p-STAT3(S727) forms. Treatment with the STAT3 degrader induced apoptosis in parental and Ven-res AML cell lines and decreased mitochondrial depolarisation, and thereby dependency on MCL1 in Ven-res AML cell line, as observed by BH3 profiling assay. STAT3 degrader treatment also enhanced differentiation of myeloid and erythroid colonies in Ven-res peripheral blood mononuclear cells (PBMNCs). Upregulation of p-STAT3(S727) was also associated with pronounced mitochondrial structural and functional dysfunction in Ven-res cell lines, that were restored by STAT3 degradation. Treatment with a clinical-stage STAT3 degrader, KT-333 resulted in a significant reduction in STAT3 and MCL1 protein levels within two weeks of treatment in a cell derived xenograft model of Ven-res AML. Additionally, this treatment significant improvement in the survival of a Ven-res patient-derived xenograft in-vivo study. Degradation of STAT3 resulting in downregulation of MCL1 and improvements in global mitochondrial dysfunction suggests a novel mechanism of overcoming Ven-res in AML. Statement of Purpose: Five-year survival from AML is dismal at 30%. Our prior research demonstrated STAT3 over-expression in AML HSPC's to be associated with inferior survival. We now explore STAT3 over-expression in Ven-res AML, explain STAT3 mediated mitochondrial perturbations and describe a novel therapeutic strategy, STAT3 degradation to overcome Ven-res.

Renal Neoplasms with Concurrent Castleman-Like Regional Lymphadenopathy.

INTRODUCTION: Renal cell neoplasms are known to be associated with paraneoplastic syndromes, and the association with Castleman-like regional lymphadenopathy has been rarely reported. We aim to characterize the association between renal neoplasms and Castleman-like lymphadenopathy. METHODS: A search for renal neoplasms with concurrent Castleman-like lymphadenopathy in one single medical institution from 2000 to 2023 resulted in 4 specimens. A literature search for "Castleman" and "renal neoplasm" resulted in 8 reports. Patients' demographics, clinical presentation, gross and histologic features, results of ancillary studies, treatment, and follow-up were evaluated. RESULTS: Our patients included 3 men and 1 woman, with a mean age of 60 years. Four different subtypes of renal neoplasms were diagnosed, including clear cell renal cell carcinoma (RCC), papillary RCC, chromophobe RCC, and mucinous cystadenoma of the renal pelvis. For Castleman-like regional lymphadenopathy, 2 were plasma-cell predominant, and 2 were hyaline-vascular. After a median follow-up of 84 months, all patients were alive with no recurrence or progression of Castleman-like features following nephrectomies. CONCLUSION: Castleman-like regional lymphadenopathy should be considered in patients with renal tumors and lymphadenopathy. Although more prevalent in clear cell RCC, it can be also associated with other renal neoplasms. The concurrent lymphadenopathy was remitted following the renal tumor resections.

Dilated aorta in CNOT3 -related neurodevelopmental disorder: 'expanding' the phenotype.

INTRODUCTION: Neurodevelopmental disorders (NDDs) comprise conditions that emerge during the child's development and contribute significantly to global health and economic burdens. De novo variants in CNOT3 have been linked to NDDs and understanding the genotype-phenotype relationship between CNOT3 and NDDs will aid in improving diagnosis and management. METHODS: In this study, we report a case of a patient with CNOT3 -related NDD who presented with progressive aortic dilatation, a feature not reported previously. RESULTS: Our patient presented with intellectual disorder, dysmorphic facial features, and cardiac anomalies, notably progressive aortic dilatation - a novel finding in CNOT3 -related NDD. Genetic testing identified a de novo 6.3 kbp intragenic deletion in CNOT3 , providing a possible genetic basis for her condition. CONCLUSION: This study presents the first case of CNOT3 -related NDD in Southeast Asia, expanding the phenotype to include progressive aortic dilatation and suggesting merit in cardiac surveillance of patients with CNOT3 -related NDD. It also emphasizes the importance of genetic testing in diagnosing complex NDD cases as well as reanalysis of 'negative' cases using advanced sequencing technologies to uncover potential hidden genetic etiologies in undiagnosed NDDs.

TNFSF9 Is Associated with Favorable Tumor Immune Microenvironment in Patients with Renal Cell Carcinoma Who Are Treated with the Combination Therapy of Nivolumab and Ipilimumab.

Combination therapy of nivolumab and ipilimumab (NIVO + IPI) for metastatic renal cell carcinoma (mRCC) has shown efficacy, but approximately 20% of patients experience disease progression in the early stages of treatment. No useful biomarkers have been reported to date. Therefore, it is desirable to identify biomarkers to predict treatment responses in advance. We examined the tumor microenvironment (TME)-related gene expression in mRCC patients treated with NIVO + IPI, between the response and non-response groups, using tumor tissues, before administering NIVO + IPI. In TME-related genes, TNFSF9 expression was identified as a candidate for the predictive biomarker. Its expression discriminated between the response and non-response groups with 88.89% sensitivity and 87.50% specificity (AUC = 0.9444). We further analyzed the roles of TNFSF9 in TME using bioinformatics from The Cancer Genome Atlas (TCGA) cohort. An adaptive immune response was activated in the TNFSF9-high-expression tumors. Indeed, T follicular helper cells, plasma B cells, and tumor-infiltrating CD8+ T cells were increased in the tumors, which indicates the promotion of humoral immunity due to enhanced T-B interactions. However, as the number of regulatory T cells (Treg) increased in the tumors, the percentage of dysfunctional T cells also increased. This suggests that not only PD-1 but also CTLA-4 inhibition may have suppressed Treg activation and improved the therapeutic effect in the TNFSF9 high-expression tumors. Therefore, TNFSF9 may predict the therapeutic efficacy of NIVO + IPI for mRCC and allow more appropriate patient selection.

Septins function in exocytosis via physical interactions with the exocyst complex in fission yeast cytokinesis.

Septins can function as scaffolds for protein recruitment, membrane-bound diffusion barriers, or membrane curvature sensors. Septins are important for cytokinesis, but their exact roles are still obscure. In fission yeast, four septins (Spn1 to Spn4) accumulate at the rim of the division plane as rings. The octameric exocyst complex, which tethers exocytic vesicles to the plasma membrane, exhibits a similar localization and is essential for plasma membrane deposition during cytokinesis. Without septins, the exocyst spreads across the division plane but absent from the rim during septum formation. These results suggest that septins and the exocyst physically interact for proper localization. Indeed, we predicted six pairs of direct interactions between septin and exocyst subunits by AlphaFold2 ColabFold, most of them are confirmed by co-immunoprecipitation and yeast two-hybrid assays. Exocyst mislocalization results in mistargeting of secretory vesicles and their cargos, which leads to cell-separation delay in septin mutants. Our results indicate that septins guide the targeting of exocyst complex on the plasma membrane for vesicle tethering during cytokinesis through direct physical interactions.

Evaluation of Collagen Dermal Filler with Lidocaine for the Correction of Nasolabial Folds: A Randomized, Double-Blind, Multicenter Clinical Trial.

Purpose: Porcine-based dermal injectable collagen is effective for nasolabial fold correction. In the present study, a new dermal injectable collagen, incorporating a novel cross-linking technology and premixed with lidocaine, was introduced. The study aimed to determine the efficacy of the new dermal injectable collagen in improving bilateral nasolabial fold wrinkles, and reducing pain during injection. Patients and Methods: This prospective, double-blind, multicenter, parallel-group, randomized trial enrolled participants with moderate-to-severe bilateral nasolabial fold wrinkles from February 2019 to March 2021. Participants were randomly assigned to the test group (new dermal injectable collagen with lidocaine featuring a novel cross-linking technology) or control group (traditionally cross-linked dermal injectable collagen with lidocaine). Participants were monitored for adverse events (AEs), and for pain using the Thermometer Pain Scale (TPS) and a visual analog scale (VAS). Efficacy was measured using the Wrinkle Severity Rating Scale (WSRS) and the Global Aesthetic Improvement Scale (GAIS). Results: On the poor or better sides, the 2 groups exhibited a significant decrease in WSRS scores at 4, 12, 24, and 36 weeks after treatment, compared to baseline WSRS scores (all, p < 0.05). Compared to the control group, the test group had a greater decrease in WSRS score (poor or better sides) at 12, 24, 36, and 52 weeks after treatment (all, p < 0.05). A similar observation was also found in the WSRS response rate and GAIS score of the 2 groups. VAS and TPS scores were not significantly different between the 2 groups (p > 0.05), indicating that pain reduction was similar in the 2 groups. All AEs were anticipated AEs associated with facial aesthetic injections, and most recovered within 0 to 30 days without sequelae. There were no differences in AEs between the 2 groups (all, p > 0.05). Conclusion: The new dermal injectable collagen with lidocaine exhibited better efficacy for correcting nasolabial fold wrinkles compared to the control group. Both relieved pain and produced only transient and tolerable AEs.

Network pharmacology analysis and molecular mechanism of paeoniflorin and its metabolite in prolactinoma cells.

Prolactinoma was the most common functional pituitary neuroendocrine tumor tissue type, which was caused by excessive proliferation of pituitary prolactin (PRL) cells. Drug therapy of dopamine receptor agonists was generally considered as the prior treatment for prolactinoma patients. However, there were still prolactinoma patients who were resistant to dopamine agonists. Studies have been reported that paeoniflorin can inhibit the secretion of PRL in prolactinoma cells lacking dopamine D2 receptor (D2R) expression, and paeoniflorin can be metabolized into albiflorin by intestinal flora in rats. The effect of albiflorin on prolactinoma has not been reported yet. In this study, network pharmacology was used to analyze the mechanism of paeoniflorin and its metabolite albiflorin as multi-target therapy for prolactinoma, and the experimental verification was carried out. In order to clarify the complex relationship among paeoniflorin, albiflorin and prolactinoma, we constructed a component-target-disease network, and further constructed interaction network, MMP9, EGFR, FGF2, FGFR1 and LGALS3 were screened as the core targets. Kyoto encyclopedia of genes and genomes (KEGG) analysis showed that paeoniflorin and albiflorin may be involved in various pathways in the treatment of prolactinoma, included relaxin signaling pathway and PI3K-Akt signaling pathway. Molecular docking analysis showed that paeoniflorin and albiflorin had good binding activity with MMP9. Western blotting results showed that paeoniflorin and albiflorin could significantly reduce the expression of MMP9, and ELISA results showed that paeoniflorin and albiflorin could significantly reduce the concentration of PRL in GH3 cells, and the reduce degree of albiflorin was stronger than paeoniflorin at 50 µM, which indicated that albiflorin might be a potential drug to treat prolactinoma, which can regulate prolactinoma through MMP9 and reduce the concentration of PRL. Our study provided a new therapeutic strategy for prolactinoma.

Enhancing Badminton Game Analysis: An Approach to Shot Refinement via a Fusion of Shuttlecock Tracking and Hit Detection from Monocular Camera.

Extracting the flight trajectory of the shuttlecock in a single turn in badminton games is important for automated sports analytics. This study proposes a novel method to extract shots in badminton games from a monocular camera. First, TrackNet, a deep neural network designed for tracking small objects, is used to extract the flight trajectory of the shuttlecock. Second, the YOLOv7 model is used to identify whether the player is swinging. As both TrackNet and YOLOv7 may have detection misses and false detections, this study proposes a shot refinement algorithm to obtain the correct hitting moment. By doing so, we can extract shots in rallies and classify the type of shots. Our proposed method achieves an accuracy of 89.7%, a recall rate of 91.3%, and an F1 rate of 90.5% in 69 matches, with 1582 rallies of the Badminton World Federation (BWF) match videos. This is a significant improvement compared to the use of TrackNet alone, which yields 58.8% accuracy, 93.6% recall, and 72.3% F1 score. Furthermore, the accuracy of shot type classification at three different thresholds is 72.1%, 65.4%, and 54.1%. These results are superior to those of TrackNet, demonstrating that our method effectively recognizes different shot types. The experimental results demonstrate the feasibility and validity of the proposed method.

Membrane protein MHZ3 regulates the on-off switch of ethylene signaling in rice.

Ethylene regulates plant growth, development, and stress adaptation. However, the early signaling events following ethylene perception, particularly in the regulation of ethylene receptor/CTRs (CONSTITUTIVE TRIPLE RESPONSE) complex, remains less understood. Here, utilizing the rapid phospho-shift of rice OsCTR2 in response to ethylene as a sensitive readout for signal activation, we revealed that MHZ3, previously identified as a stabilizer of ETHYLENE INSENSITIVE 2 (OsEIN2), is crucial for maintaining OsCTR2 phosphorylation. Genetically, both functional MHZ3 and ethylene receptors prove essential for OsCTR2 phosphorylation. MHZ3 physically interacts with both subfamily I and II ethylene receptors, e.g., OsERS2 and OsETR2 respectively, stabilizing their association with OsCTR2 and thereby maintaining OsCTR2 activity. Ethylene treatment disrupts the interactions within the protein complex MHZ3/receptors/OsCTR2, reducing OsCTR2 phosphorylation and initiating downstream signaling. Our study unveils the dual role of MHZ3 in fine-tuning ethylene signaling activation, providing insights into the initial stages of the ethylene signaling cascade.

Surgical outcomes of hidradenitis suppurativa: evaluating factors influencing recurrence and complications after 284 complete excisions.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory disorder associated with tunnel formation and scarring. Surgical excision is a potential curative therapy for HS. OBJECTIVES: To characterize the surgical outcomes of patients with HS undergoing complete excision and to identify the risk factors associated with postoperative recurrence. METHODS: This retrospective 16-year cohort study enrolled patients 20 years or older who underwent complete excision for HS lesions at the National Taiwan University Hospital. We assessed the rates of postsurgical recurrence and complications, and estimated the odds ratio (ORs) with 95% confidence intervals (CIs) of their association with potential risk factors using generalized estimating equations. RESULTS: In total, 136 patients with HS and the 284 corresponding complete excisions were identified. Recurrence developed in 88 (31.0%) operations, while complications occurred in 102 (35.9%). Common types of complications included wound dehiscence, hypertrophic scars, and surgical site infection. Clinical factors associated with a lower risk of recurrence were male sex (aOR, 0.48; 95% CI, 0.23-0.98), operation at atypical locations (aOR, 0.28; 95% CI, 0.08-0.99), and wound repair by split-thickness skin graft (aOR, 0.31; 95% CI, 0.12-0.77). Wound dehiscence was associated with an increased risk of recurrence (aOR, 2.55; 95% CI, 1.21-5.42). No independent factors were identified as being associated with composite postoperative complications. CONCLUSIONS: Complete excision alone is effective in curing HS in Asians. Recurrence developed in about one-third of the complete excisions performed for HS. Sex, operative locations, methods of wound repair, and wound dehiscence were major determinants for recurrence.

A cross-sectional analysis of gender and psychological well-being among older Taiwanese adults.

Background: Psychological well-being (PWB) facilitates good health. Few studies have taken into consideration gender and how it can affect PWB within a sociocultural context. This study aims to determine if relationships between social, health, behavioral, and socioeconomic factors on PWB among older Taiwanese adults are affected by gender. Methods: Data were obtained from the 2016 Taiwan Mental Health Survey. A representative sample, of 2,286 individuals, was created using multistage proportional probability. Participants were interviewed at their homes using a structured questionnaire. Inclusion criteria were Taiwanese citizenship, age ≥ 55 years, and the ability to provide informed consent. Participants 65 years and above were selected for the study sample n = 1,533. An 18-item version of Ryff's PWB scale was used to determine PWB. The median value was used to categorize low and high PWB. Logistic regression analyses were used to examine predictors of PWB stratified by gender. Results: Chronic disease, unemployment, and financial dependence negatively impacted men's PWB. Satisfaction with living environment and family relationships positively impacted women's PWB. Unique characteristics of older men, women, and culture account for this. Conclusion: Gender-specific interventions aimed at promoting PWB in older adults are needed. Recommendations include educational programs, social support workshops, and community engagement initiatives.