Open-ICL: Open-Set Modulation Classification via Incremental Contrastive Learning.

Open-set modulation classification (OMC) of signals is a challenging task for handling "unknown" modulation types that are not included in the training dataset. This article proposes an incremental contrastive learning method for OMC, called Open-ICL, to accurately identify unknown modulation types of signals. First, a dual-path 1-D network (DONet) with a classification path (CLP) and a contrast path (COP) is designed to learn discriminative signal features cooperatively. In the COP, the deep features of the input signal are compared with the semantic feature centers (SFCs) of known classes calculated from the network, to infer its signal novelty. An unknown signal bank (USB) is defined to store unknown signals, and a novel moving intersection algorithm (MIA) is proposed to dynamically select reliable unknown signals for the USB. The "unknown" instances, together with SFCs, are continuously optimized and updated, facilitating the process of incremental learning. Furthermore, a dynamic adaptive threshold (DAT) strategy is proposed to enable Open-ICL to adaptively learn changing signal distributions. Extensive experiments are performed on two benchmark datasets, and the results demonstrate the effectiveness of Open-ICL for OMC.

Prognostic Understanding, Goals of Care, and Quality of Life in Hospitalized Patients with Leukemia or Multiple Myeloma.

Background: Prior studies reveal a lack of illness understanding and prognostic awareness among patients with hematological malignancies. We evaluated prognostic awareness and illness understanding among patients with acute leukemia and multiple myeloma (MM) and measured patient-hematologist discordance. Methods: We prospectively enrolled patients with acute leukemia and MM at Mount Sinai Hospital or Yale New Haven Hospital between August 2015 and February 2020. Patients were administered a survey assessing prognostic awareness, goals of care (GOC), and quality of life. Hematologists completed a similar survey for each patient. We assessed discordance across the cohort of patients and hematologists using the likelihood-ratio chi-square test and within patient-hematologist pairs using the kappa (κ) statistic. Results: We enrolled 185 patients (137 with leukemia and 48 with MM) and 29 hematologists. Among patients, 137 (74%) self-identified as White, 27 (15%) as Black, and 21 (11%) as Hispanic. Across the entire cohort, patients were significantly more optimistic about treatment goals compared with hematologists (p = 0.027). Within patient-hematologist pairs, hematologists were significantly more optimistic than patients with respect to line of treatment (κ = 0.03). For both leukemia and MM cohorts, patients were significantly more likely to respond "don't know" or deferring to a faith-based response with 88 (64%) and 34 (71%), respectively, compared with only 28 (20%) and 11 (23%) of hematologists, respectively. Conclusions: We observed significant discordance regarding prognosis and GOC among patients with hematological malignancies and their hematologists. These data support future interventions to improve prognostic understanding among this patient population to facilitate informed treatment choices.

Blood-Catalyzed Polymerization Creates Conductive Polymer in Live Zebrafish.

Conducting polymers are of great interest in bioimaging, bio-interfaces, and bioelectronics for their biocompatibility and the unique combination of optical, electrical, and mechanical properties. They are typically prepared outside through traditional organic synthesis and delivered into the biological systems. The ability to call for the polymerization ingredients available inside the living systems to generate conducting polymers in vivo will offer new venues in future biomedical applications. This study is the first report of in vivo synthesis of an n-doped conducting polymer (n-PBDF) within live zebrafish embryos, achieved through whole blood catalyzed polymerization of 3,7-dihydrobenzo[1,2-b:4,5-b']difuran-2,6-dione (BDF). Prior to this, the efficacy of such a polymerization was rigorously established through a sequence of in vitro experiments involving Hemin, Hemoproteins (Hemoglobin, Myoglobin, and Cytochrome C), red blood cells, and the whole blood. Ultimately, in cellulo formed n-PBDF within cultured primary neurons demonstrated enhanced bio-interfaces and led to more effective light-induced neural activation than the prefabricated polymer. This underscores the potential advantages of synthesizing conducting polymers directly in living systems for biomedical applications.

Association between spectrum of mycotoxins and semen quality: A cross-sectional study in Beijing, China.

Exposure to mycotoxins is unavoidable in daily life through ingestion, dermal, and inhalation routes. Toxicological studies found that exposure to mycotoxins might affect male reproductive function. However, there is still a lack of population evidence. We aimed to assess the association of individual and joint exposure to spectrum of mycotoxins with semen quality. The present study included 192 participants in Beijing, China. We measured conventional semen parameters and assessed semen quality. Sixty-seven traditional or emerging mycotoxins were determined to describe the spectrum of mycotoxins. The participants were widely exposed to multiple mycotoxins, and nearly half were simultaneously exposed to more than six mycotoxins. After adjusting potential confounders, logistic regression indicated that the number and concentration of plasma mycotoxin were correlated to the risk of low semen quality. Plasma beauvericin and citrinin concentrations were associated with lower semen quality. The least absolute shrinkage and selection operator regression showed similar results to logistic regression. Quantile-based g-computation and Bayesian kernel machine regression models found that the mixture of mycotoxins was harmful to semen quality, especially in sperm motility. In conclusion, both individual and mixture of mycotoxin exposure were correlated with lower semen quality. More regulations and measures should be taken to reduce mycotoxin contamination.

A comparative analysis of different reduced-port laparoscopic surgical procedures after non-curative endoscopic resection for early colorectal cancer.

Introduction: Surgery serves as a salvage procedure for non-curative resection of early-stage colorectal cancer under endoscopy. A standard method for performing additional surgery after endoscopic submucosal dissection (ESD) for early colorectal cancer has yet to be established. Aim: To enhance the understanding of different surgical outcomes by discussing additional treatment strategies following non-complete curative endoscopic resection of early colorectal cancer. Material and methods: This retrospective study included 88 patients who were divided into three groups based on the surgical approach: conventional laparoscopic surgery (CLS), single-incision plus one-port laparoscopic surgery (SILS+1), and three-port laparoscopic surgery combined with natural orifice specimen extraction surgery (three-port NOSES). The study aimed to compare the surgical outcomes, safety, and postoperative recovery among these groups. Results: The SILS+1 and three-port NOSES groups demonstrated comparable safety and efficacy to the CLS group in terms of blood loss, complications, number of lymph node dissections, and length of bowel resection. However, the SILS+1 and three-port NOSES groups had advantages in terms of incision length (7.11 ±0.38, 4.24 ±0.33, 3.16 ±0.22, p < 0.001), postoperative pain (4.000 [3.0,5.0], 3.500 [3.0,4.0], 3.000 [3.0,4.0]; p = 0.003), cosmetic result (4.000 [3.8,5.0], 7.000 [7.0,8.0], 7.000 [7.0,8.0]; p < 0.001), and hospital stay (8.000 [7.0,9.0], 7.000 [6.3,8.0.], 7.000 [6.3,8.0]; p = 0.035). Conclusions: Different strategies of reduced-port laparoscopic surgery have been demonstrated to be effective and safe in additional surgery after non-curative ESD. These techniques have shown reduced pain and increased satisfaction among patients. Reduced-port laparoscopic surgery is expected to become the preferred treatment option for these patients.

Correction: Phosphorescent [3 + 2 + 1] coordinated Ir(iii) cyano complexes for achieving efficient phosphors and their application in OLED devices.

[This corrects the article DOI: 10.1039/D1SC01426A.].

Mid-Infrared Photoacoustic Stimulation of Neurons through Vibrational Excitation in Polydimethylsiloxane.

Photoacoustic (PA) emitters are emerging ultrasound sources offering high spatial resolution and ease of miniaturization. Thus far, PA emitters rely on electronic transitions of absorbers embedded in an expansion matrix such as polydimethylsiloxane (PDMS). Here, it is shown that mid-infrared vibrational excitation of C─H bonds in a transparent PDMS film can lead to efficient mid-infrared photoacoustic conversion (MIPA). MIPA shows 37.5 times more efficient than the commonly used PA emitters based on carbon nanotubes embedded in PDMS. Successful neural stimulation through MIPA both in a wide field with a size up to a 100 µm radius and in single-cell precision is achieved. Owing to the low heat conductivity of PDMS, less than a 0.5 °C temperature increase is found on the surface of a PDMS film during successful neural stimulation, suggesting a non-thermal mechanism. MIPA emitters allow repetitive wide-field neural stimulation, opening up opportunities for high-throughput screening of mechano-sensitive ion channels and regulators.

Single-cell transcriptomic analysis identifies downregulated phosphodiesterase 8B as a novel oncogene in IDH-mutant glioma.

Introduction: Glioma, a prevalent and deadly brain tumor, is marked by significant cellular heterogeneity and metabolic alterations. However, the comprehensive cell-of-origin and metabolic landscape in high-grade (Glioblastoma Multiforme, WHO grade IV) and low-grade (Oligoastrocytoma, WHO grade II) gliomas remains elusive. Methods: In this study, we undertook single-cell transcriptome sequencing of these glioma grades to elucidate their cellular and metabolic distinctions. Following the identification of cell types, we compared metabolic pathway activities and gene expressions between high-grade and low-grade gliomas. Results: Notably, astrocytes and oligodendrocyte progenitor cells (OPCs) exhibited the most substantial differences in both metabolic pathways and gene expression, indicative of their distinct origins. The comprehensive analysis identified the most altered metabolic pathways (MCPs) and genes across all cell types, which were further validated against TCGA and CGGA datasets for clinical relevance. Discussion: Crucially, the metabolic enzyme phosphodiesterase 8B (PDE8B) was found to be exclusively expressed and progressively downregulated in astrocytes and OPCs in higher-grade gliomas. This decreased expression identifies PDE8B as a metabolism-related oncogene in IDH-mutant glioma, marking its dual role as both a protective marker for glioma grading and prognosis and as a facilitator in glioma progression.

Epigenetically associated IGF2BP3 upregulation promotes cell proliferation by regulating E2F1 expression in hepatocellular carcinoma.

RNA-binding proteins (RBPs) are a class of proteins that primarily function by interacting with different types of RNAs and play a critical role in regulating the transcription and translation of cancer-related genes. However, their role in the progression of hepatocellular carcinoma (HCC) remains unclear. In this study, we analyzed RNA sequencing data and the corresponding clinical information of patients with HCC to screen for prognostic RBPs. Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) was identified as an independent prognostic factor for liver cancer. It is upregulated in HCC and is associated with a poor prognosis. Elevated IGF2BP3 expression was validated via immunohistochemical analysis using a tissue microarray of patients with HCC. IGF2BP3 knockdown inhibited the proliferation of Hep3B and HepG2 cells, whereas IGF2BP3 overexpression promoted the expansion of HuH-7 and MHCC97H cells. Mechanistically, IGF2BP3 modulates cell proliferation by regulating E2F1 expression. DNA hypomethylation of the IGF2BP3 gene may increase the expression of IGF2BP3, thereby enhancing cell proliferation in HCC. Therefore, IGF2BP3 may act as a novel prognostic biomarker and a potential therapeutic target for HCC.

Global incidence trends of early-onset colorectal cancer and related exposures in early-life: an ecological analysis based on the GBD 2019.

Background: The incidence of early-onset colorectal cancer (EOCRC) is increasing globally. This study aims to describe the temporal trends of incidence and explore related risk exposures in early-life at the country level based on the GBD 2019. Methods: Data on the incidence and attributable risk factors of EOCRC were obtained from the GBD 2019. Temporal trends of age-standardized incidence were evaluated by average annual percentage change (AAPC). Early-life exposures were indicated as summary exposure values (SEV) of selected factors, SDI and GDP per capita in previous decades and at ages 0-4, 5-9, 10-14 and 15-19 years. Weighted linear or non-linear regressions were applied to evaluate the ecological aggregate associations of the exposures with incidences of EOCRC. Results: The global age-standardized incidence of EOCRC increased from 3.05 (3.03, 3.07) to 3.85 (3.83, 3.86) per 100,000 during 1990 and 2019. The incidence was higher in countries with high socioeconomic levels, and increased drastically in countries in East Asia and Caribbean, particularly Jamaica, Saudi Arabia and Vietnam. The GDP per capita, SDI, and SEVs of iron deficiency, alcohol use, high body-mass index, and child growth failure in earlier years were more closely related with the incidences of EOCRC in 2019. Exposures at ages 0-4, 5-9, 10-14 and 15-19 years were also associated with the incidences, particularly for the exposures at ages 15-19 years. Conclusion: The global incidence of EOCRC increased during past three decades. The large variations at regional and national level may be related with the distribution of risk exposures in early life.

Combining neuromodulation strategies in spinal cord injury gait rehabilitation: A proof of concept, randomized, crossover trial.

OBJECTIVE: To evaluate if acute intermittent hypoxia (AIH) coupled with transcutaneous spinal cord stimulation (tSCS) enhance task-specific training and lead to superior and more sustained gait improvements as compared to each of these strategies used in isolation in persons with chronic, incomplete spinal cord injury (SCI). DESIGN: Proof of concept, randomized crossover trial SETTING: Outpatient, rehabilitation hospital INTERVENTIONS: Ten participants completed 3 intervention arms: 1) AIH, tSCS, and gait training (AIH + tSCS), 2) tSCS plus gait training (SHAM AIH + tSCS), and 3) gait training alone (SHAM + SHAM). Each arm consisted of 5 consecutive days of intervention with a minimum of a 4-week washout between arms. The order of arms was randomized. The study took place from December 3, 2020 to January 4, 2023. MAIN OUTCOME MEASURES: 10-meter walk test (10MWT) at self-selected velocity (SSV) and fast velocity (FV), 6-minute walk test (6MWT), Timed Up and Go (TUG) SECONDARY OUTCOME MEASURES: Isometric ankle plantarflexion and dorsiflexion torque RESULTS: TUG improvements were 3.44 seconds (95% CI: 1.24-5.65) significantly greater in the AIH + tSCS arm than the SHAM AIH + tSCS arm at post-intervention (POST) and 3.31 seconds (95% CI: 1.03-5.58) greater than the SHAM + SHAM arm at 1-week follow up. SSV was 0.08 m/s (95% CI: 0.02-0.14) significantly greater following the AIH + tSCS arm than the SHAM AIH + tSCS at POST. Although not significant, the AIH + tSCS arm also demonstrated the greatest average improvements compared to the other two arms at POST and 1WK for the 6MWT, FV, and ankle plantarflexion torque. CONCLUSIONS: This pilot study is the first to demonstrate that combining these three neuromodulation strategies leads to superior improvements in the TUG and SSV for individuals with chronic incomplete SCI and warrants further investigation.

Neuroimmune modulating and energy supporting nanozyme-mimic scaffold synergistically promotes axon regeneration after spinal cord injury.

Spinal cord injury (SCI) represents a profound central nervous system affliction, resulting in irreversibly compromised daily activities and disabilities. SCI involves excessive inflammatory responses, which are characterized by the existence of high levels of proinflammatory M1 macrophages, and neuronal mitochondrial energy deficit, exacerbating secondary damage and impeding axon regeneration. This study delves into the mechanistic intricacies of SCI, offering insights from the perspectives of neuroimmune regulation and mitochondrial function, leading to a pro-fibrotic macrophage phenotype and energy-supplying deficit. To address these challenges, we developed a smart scaffold incorporating enzyme mimicry nanoparticle-ceriumoxide (COPs) into nanofibers (NS@COP), which aims to pioneer a targeted neuroimmune repair strategy, rescuing CGRP receptor on macrophage and concurrently remodeling mitochondrial function. Our findings indicate that the integrated COPs restore the responsiveness of pro-inflammatory macrophages to calcitonin gene-related peptide (CGRP) signal by up-regulating receptor activity modifying protein 1 (RAMP1), a vital component of the CGRP receptor. This promotes macrophage fate commitment to an anti-inflammatory pro-resolution M2 phenotype, then alleviating glial scar formation. In addition, NS@COP implantation also protected neuronal mitochondrial function. Collectively, our results suggest that the strategy of integrating nanozyme COP nanoparticles into a nanofiber scaffold provides a promising therapeutic candidate for spinal cord trauma via rational regulation of neuroimmune communication and mitochondrial function.

Development of an effective meropenem/KPC-2 inhibitor combination to combat infections caused by carbapenem-resistant K. pneumoniae.

The global public health threat of bacterial antibiotic resistance continues to escalate and necessitates the implementation of urgent measures to expand our arsenal of antimicrobial drugs. In this study, we identified a benzoxaborane compound, namely 5-chloro-1,3-dihydro-1-hydroxy-2,1-benzoxaborole (AN2178), which can effectively inhibit the catalytic activity of the Klebsiella pneumoniae carbapenemase (KPC-2) enzyme. The efficacy of AN2718 as an inhibitor for the KPC-2 enzyme was verified through various assays, including enzyme activity assays and isothermal titration calorimetry. Results of multiple biochemical assays, minimum inhibitory concentration assay, and time-killing assay also showed that binding of AN2718 to KPC-2 enabled the restoration of the bactericidal effect of meropenem. The survival rate of mice infected by carbapenem-resistant, high-virulence strains increased significantly upon treatment with this agent. Most importantly, the meropenem and AN2718 combination is effective on KPC-2 mutations such as KPC-33 that were clinically evolved and exhibited resistance to ceftazidime-avibactam upon the clinical uses of this drug for a couple of years. Comprehensive safety tests both in vitro and in vivo, such as cytotoxicity, haemolytic activity, and cytochrome P450 inhibition assays demonstrated that AN2718 was safe for clinical use. These promising data indicate that AN2718 has a high potential for being approved for the treatment of drug resistant bacterial infections, including those caused by the Ceftazidime-Avibactam resistant strains. To conclude, the compound AN2718 can be regarded as a valuable addition to the current antimicrobial armamentarium and a promising tool to combat antimicrobial resistance.

The short-term effects of Jin's three needles in conjunction with mirror therapy on brain function in patients with upper limb disability following an ischemic stroke were evaluated using ReHo analysis.

BACKGROUND: Jin's three needle (JTN) is a commonly utilized treatment for ischemic stroke in China. Mirror therapy (MT) is also gradually transitioning from treating limb discomfort to restoring motor function in the damaged limb. Investigations into the 2 treatments' mechanisms of action are still ongoing. We used functional magnetic resonance imaging (fMRI) technique in this study to examine the effects of JTN combined with mirror therapy MT on brain function in patients with upper limb dysfunction in ischemic stroke, as well as potential central mechanisms. The goal was to provide a solid evidence-based medical basis to support the continued use of JTN combination MT. METHODS: This study will be a single-blind, randomized, and controlled experiment. Randomization was used to assign 20 patients who met the study's eligibility requirements to the JTN + MT treatment group or the JTN control group. Each intervention will last for 4 weeks, with 6 days of treatment per week. The JTN acupuncture points are 3 temporal acupuncture points on the opposite side of the wounded limb, 3 hand acupuncture points on the injured upper limb, 3 shoulder acupuncture points, Renzhong and Baihui, The (JTN + MT) group simultaneously takes MT for 30 minutes. fMRI of the brain using BOLD and T1-weighted images was done both before and after therapy. Brain areas exhibiting changes in regional homogeneity during the pre and posttreatment periods were analyzed. RESULTS: By the end of the treatment course, Jin three-needle therapy plus MT activated more relevant brain functional regions and increased cerebral blood oxygen perfusion than Jin three-needle therapy alone (P <.05). CONCLUSION: In patients with upper limb impairment following an ischemic stroke, JTN with MT may improve brain function reconstruction in the relevant areas.

Treatment of myelofibrosis with refractory anemia with luspatercept: a multicenter Chinese study.

Myelofibrosis is a rare and often fatal hematological neoplasm, and the treatment of myelofibrosis-associated anemia remains suboptimal, with no improved therapies. Luspatercept was shown to display some efficacy in a phase 2 clinical trial for Myelofibrosis with anemia, yet relevant research are limited. Threrfore, data from patients diagnosed with refractory anemic primary or post-essential thrombocythemia/polycythemia vera myelofibrosis, who were treated with luspatercept for at least 9 weeks, were retrospectively collected. Eighteen patients with myelofibrosis treated with luspatercept were enrolled. Median age was 68 years (range, 44-80 years), and 27.8% were males. Ten (55.6%) were transfusion-dependent. Ten (55.6%) were Dynamic International Prognostic Scoring System intermediate-1, and eight (44.4%) were intermediate-2. The median follow-up was 7 (4-16) months. Erythroid response occurred in eight patients (44.4%) at week 12, four patients (30.8%) at week 24, and nine (50%) at the end of follow-up. Patients who were transfusion-dependent and not transfusion-dependent had similar HI-E responses, at different time points (P > 0.05). Patients had a significantly higher hemoglobin level at 12 weeks, 24 weeks, and at the end of follow-up, than at baseline (P = 0.001, P = 0.021, and P = 0.005, respectively). Treatment-related adverse events occurred in five (16.7%) patients, with no serious adverse events. Two (11.1%) patients relapsed at weeks 15 and 31. One patient progressed to acute myeloid leukemia. No patients had died by the end of follow-up. Luspatercept induced a good response in patients with anemic myelofibrosis, with a low relapse rate and good tolerance.

Twelve-Month Outcomes of Three Episcleral Surgeries in Treatment of Rhegmatogenous Retinal Detachment.

INTRODUCTION: To compare the long-term outcomes of conventional scleral buckling (CSB), modified scleral buckling (MSB), and scleral encircling (SE) in the treatment of rhegmatogenous retinal detachment and identify factors influencing the outcomes. METHODS: This comparative, retrospective cohort study assigned patients to CSB, MSB, and SE groups. The follow-up was 12 months, and the reattachment rate, complication rate, visual acuity, number of newly discovered tears during surgery, and changes in diopters were compared among the three surgeries. Influential factors on anatomical and functional reattachment were identified. RESULTS: There were no significant differences in the primary reattachment rate, overall complication rate, or best-corrected visual acuity at 6 or 12 months among the three groups. The MSB group had a higher number of newly discovered tears during surgery compared with the other two groups. At 12 months post-surgery, the SE group displayed the greatest change of diopter, whereas the MSB group showed the least change. The surgical approach did not influence the primary reattachment rate. Long-term visual outcomes were influenced by factors including sex, preoperative visual acuity, macular status, and duration of symptoms. CONCLUSION: MSB is an effective method for treating rhegmatogenous retinal detachment. Its advantages include the ability to identify smaller tears and induce minimal changes in diopter.

Sesame lignans modulate aroma formation in sesame oil through the Maillard reaction and lipid oxidation in model systems.

The unknown effect of sesame lignans on aroma formation in sesame oil via the Maillard reaction (MR) and lipid oxidation was investigated. Sesamin, sesamolin, or sesamol was added to 3 models: lysine+glucose (MR), cold-pressed sesame oil (SO), and MR + SO, and were heated at 120 °C for 60 min. All three lignans suppressed SO oxidation while increasing DPPH scavenging ability (p < 0.05). Lignans increased depletions of lysine and glucose and MR browning (p < 0.05). Lignans reduced most aroma-active pyrazines, aldehydes, ketones, alcohols, and esters (p < 0.05). Sesamol and sesamolin increased perceptions of the preferable aromas of nutty, roasted sesame, and popcorn while reducing the undesirable green and rancid aromas (p < 0.05). Sesamol demonstrated a stronger effect on lipid oxidation, MR browning, aroma formation, and sensory perception than sesamin and sesamolin. This study suggests that sesame lignans can modulate aroma formation and sensory perception of sesame oil by interacting with the MR and lipid oxidation pathways.

1,25-Dihydroxyvitamin D3 Suppresses UV-Induced Poly(ADP-Ribose) Levels in Primary Human Keratinocytes, as Detected by a Novel Whole-Cell ELISA.

Photoprotective properties of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) to reduce UV-induced DNA damage have been established in several studies. UV-induced DNA damage in skin such as single or double strand breaks is known to initiate several cellular mechanisms including activation of poly(ADP-ribose) (pADPr) polymerase-1 (PARP-1). DNA damage from UV also increases extracellular signal-related kinase (ERK) phosphorylation, which further increases PARP activity. PARP-1 functions by using cellular nicotinamide adenine dinucleotide (NAD+) to synthesise pADPr moieties and attach these to target proteins involved in DNA repair. Excessive PARP-1 activation following cellular stress such as UV irradiation may result in excessive levels of cellular pADPr. This can also have deleterious effects on cellular energy levels due to depletion of NAD+ to suboptimal levels. Since our previous work indicated that 1,25(OH)2D3 reduced UV-induced DNA damage in part through increased repair via increased energy availability, the current study investigated the effect of 1,25(OH)2D3 on UV-induced PARP-1 activity using a novel whole-cell enzyme- linked immunosorbent assay (ELISA) which quantified levels of the enzymatic product of PARP-1, pADPr. This whole cell assay used around 5000 cells per replicate measurement, which represents a 200-400-fold decrease in cell requirement compared to current commercial assays that measure in vitro pADPr levels. Using our assay, we observed that UV exposure significantly increased pADPr levels in human keratinocytes, while 1,25(OH)2D3 significantly reduced levels of UV-induced pADPr in primary human keratinocytes to a similar extent as a known PARP-1 inhibitor, 3-aminobenzamide (3AB). Further, both 1,25(OH)2D3 and 3AB as well as a peptide inhibitor of ERK-phosphorylation significantly reduced DNA damage in UV-exposed keratinocytes. The current findings support the proposal that reduction in pADPr levels may be critical for the function of 1,25(OH)2D3 in skin to reduce UV-induced DNA damage.

High prevalence of vitamin D deficiency in Taiwanese patients with inflammatory bowel disease.

Vitamin D deficiency is common in patients with inflammatory bowel disease (IBD). In this study, we aimed to evaluate the prevalence and risk factors of vitamin D deficiency in a Taiwanese IBD cohort. Vitamin D levels were checked in adult patients with IBD who were treated at Changhua Christian Hospital, a medical center in central Taiwan, from January 2017 to December 2023. The risk factors for vitamin D deficiency were evaluated. 106 adult IBD patients were included, including 20 patients with Crohn's disease and 86 with ulcerative colitis. The median age at diagnosis was 39.2 years. The mean vitamin D level was 22.2 ± 8 ng/mL. Forty-five patients (42.5%) had vitamin D deficiency (vitamin D level < 20 ng/mL). Comparing patients with normal vitamin D levels and those with vitamin D deficiency after multivariate adjustment, female sex and early age at diagnosis were identified as statistically significant risk factors. We found a prevalence of 42.5% of vitamin D deficiency in the Taiwanese IBD population. Understanding this issue is essential for teaching patients and doctors about vitamin D deficiency screening and improving patient outcomes.

CircVIRMA enhances cell malignant behavior by governing the miR-452-5p/CREBRF pathway in cervical cancer.

Our current study aimed to investigate the role and mechanism of circVIRMA in cervical cancer (CC) progression. CircVIRMA, microRNA-452-5p (miR-452-5p) and CREB3 regulatory factor (CREBRF) mRNA levels were examined in CC via quantitative real-time PCR (qRT-PCR). The protein level of CREBRF in CC was checked by Western blot. Cell Counting Kit-8 (CCK-8), colony formation, 5-Ethynyl-2'-deoxyuridine (EdU) staining, cell cycle, flow cytometry and transwell assays were conducted to estimate the effects of circVIRMA on malignant phenotypes of CC tumors. Western blot was used to measure related marker protein levels. The interaction between miR-452-5p and circVIRMA or CREBRF was predicted by bioinformatics analysis and verified by dual-luciferase reporter and RNA Immunoprecipitation (RIP) assays. Xenograft assay was used to assess the effect of circVIRMA on tumor growth in vivo. Immunohistochemistry (IHC) assay was performed to detect Ki-67 expression in tissues of mice. CircVIRMA and CREBRF levels were upregulated, while miR-452-5p was downregulated in CC tissues and cells. CircVIRMA silencing restrained CC cell proliferation, migration and invasion whereas induced apoptosis in vitro. In addition circVIRMA knockdown markedly attenuated xenograft tumor growth in vivo. circVIRMA was an efficient molecular sponge for miR-452-5p, and negatively regulated miR-452-5p expression. circVIRMA regulated CREBRF expression to modulate CC progression via miR-452-5p. MiR-452-5p downregulation reversed the effects of circVIRMA knockdown on CC progression. MiR-452-5p directly targeted CREBRF, and CREBRF overexpression partly restored the impact of miR-452-5p mimics on CC progression. circVIRMA mediated CC progression via regulating miR-452-5p/CREBRF axis, providing a novel therapeutic target for CC treatment.