Chromosome-scale reference genome of broccoli (Brassica oleracea var. italica Plenck) provides insights into glucosinolate biosynthesis.

Broccoli (Brassica oleracea var. italica Plenck) is an important vegetable crop, as it is rich in health-beneficial glucosinolates (GSLs). However, the genetic basis of the GSL diversity in Brassicaceae remains unclear. Here we report a chromosome-level genome assembly of broccoli generated using PacBio HiFi reads and Hi-C technology. The final genome assembly is 613.79 Mb in size, with a contig N50 of 14.70 Mb. The GSL profile and content analysis of different B. oleracea varieties, combined with a phylogenetic tree analysis, sequence alignment, and the construction of a 3D model of the methylthioalkylmalate synthase 1 (MAM1) protein, revealed that the gene copy number and amino acid sequence variation both contributed to the diversity of GSL biosynthesis in B. oleracea. The overexpression of BoMAM1 (BolI0108790) in broccoli resulted in high accumulation and a high ratio of C4-GSLs, demonstrating that BoMAM1 is the key enzyme in C4-GSL biosynthesis. These results provide valuable insights for future genetic studies and nutritive component applications of Brassica crops.

A novel protein CYTB-187AA encoded by the mitochondrial gene CYTB modulates mammalian early development.

The mitochondrial genome transcribes 13 mRNAs coding for well-known proteins essential for oxidative phosphorylation. We demonstrate here that cytochrome b (CYTB), the only mitochondrial-DNA-encoded transcript among complex III, also encodes an unrecognized 187-amino-acid-long protein, CYTB-187AA, using the standard genetic code of cytosolic ribosomes rather than the mitochondrial genetic code. After validating the existence of this mtDNA-encoded protein arising from cytosolic translation (mPACT) using mass spectrometry and antibodies, we show that CYTB-187AA is mainly localized in the mitochondrial matrix and promotes the pluripotent state in primed-to-naive transition by interacting with solute carrier family 25 member 3 (SLC25A3) to modulate ATP production. We further generated a transgenic knockin mouse model of CYTB-187AA silencing and found that reduction of CYTB-187AA impairs females' fertility by decreasing the number of ovarian follicles. For the first time, we uncovered the novel mPACT pattern of a mitochondrial mRNA and demonstrated the physiological function of this 14th protein encoded by mtDNA.

Association of diarrhea or constipation with urinary incontinence in adults: A cross-sectional analysis of the National Health and Nutrition Examination Survey.

AIMS: This study aimed to investigate the association between diarrhea or constipation and urinary incontinence (UI) in adults. METHODS: Data from the National Health and Nutrition Examination Survey for 2009-2010 was used to include 4686 adults aged 20 and over in the analysis. Stress urinary incontinence (SUI) and urgency urinary incontinence (UUI) were used as outcome variables, with diarrhea and constipation as exposure factors. We first compared the baseline characteristics of those with and without SUI, as well as those with and without UUI. The impact of diarrhea or constipation on SUI and UUI was assessed using multivariate logistic regression models. To ensure the stability of the results, subgroup and stratified analyses were conducted. RESULTS: The prevalence rates of UUI and SUI were 22.49% and 23.39%, respectively. Adjusted multivariate logistic regression analysis revealed that the risk of UUI was increased by either diarrhea (OR 1.66, 95% CI 1.36-2.04) or constipation (OR 1.42, 95% CI 1.11-1.83). The risk of SUI was also elevated by either diarrhea (OR 1.36, 95% CI 1.11-1.67) or constipation (OR 1.32, 95% CI 1.06-1.63). Subgroup analysis revealed no significant differences in the interaction tests between constipation or diarrhea and UI. CONCLUSIONS: This study found that both constipation and diarrhea increase the risk of UUI and SUI.

Asymmetric silicon phthalocyanine based nanoparticle with spatiotemporally targeting of mitochondria for synergistic apoptosis-ferroptosis antitumor treatment.

A promising therapeutic strategy in cancer treatment merges photodynamic therapy (PDT) induced apoptosis with ferroptosis, a form of programmed cell death governed by iron-dependent lipid peroxidation. Given the pivotal role of mitochondria in ferroptosis, the development of photosensitizers that specifically provoke mitochondrial dysfunction and consequentially trigger ferroptosis via PDT is of significant interest. To this end, we have designed and synthesized a novel nanoparticle, termed FECTPN, tailored to address this requisite. FECTPN harnesses a trifecta of critical attributes: precision mitochondria targeting, photoactivation capability, pH-responsive drug release, and synergistic apoptosis-ferroptosis antitumor treatment. This nanoparticle was formulated by conjugating an asymmetric silicon phthalocyanine, Chol-SiPc-TPP, with the ferroptosis inducer Erastin onto a ferritin. The Chol-SiPc-TPP is a chemically crafted entity featuring cholesteryl (Chol) and triphenylphosphine (TPP) functionalities bonded axially to the silicon phthalocyanine, enhancing mitochondrial affinity and leading to effective PDT and subsequent apoptosis of cells. Upon cellular uptake, FECTPN preferentially localizes to mitochondria, facilitated by Chol-SiPc-TPP's targeting mechanics. Photoactivation induces the synchronized release of Chol-SiPc-TPP and Erastin in the mitochondria's alkaline domain, driving the escalation of both ROSs and lipid peroxidation. These processes culminate in elevated antitumor activity compared to the singular application of Chol-SiPc-TPP-mediated PDT. A notable observation is the pronounced enhancement in glutathione peroxidase-4 (GPX4) expression within MCF-7 cells treated with FECTPN and subjected to light exposure, reflecting intensified oxidative stress. This study offers compelling evidence that FECTPN can effectively induce ferroptosis and reinforces the paradigm of a synergistic apoptosis-ferroptosis pathway in cancer therapy, proposing a novel route for augmented antitumor treatments.

Characterization of gene regulatory networks underlying key properties in human hematopoietic stem cell ontogeny.

Human hematopoiesis starts at early yolk sac and undergoes site- and stage-specific changes over development. The intrinsic mechanism underlying property changes in hematopoiesis ontogeny remains poorly understood. Here, we analyzed single-cell transcriptome of human primary hematopoietic stem/progenitor cells (HSPCs) at different developmental stages, including yolk-sac (YS), AGM, fetal liver (FL), umbilical cord blood (UCB) and adult peripheral blood (PB) mobilized HSPCs. These stage-specific HSPCs display differential intrinsic properties, such as metabolism, self-renewal, differentiating potentialities etc. We then generated highly co-related gene regulatory network (GRNs) modules underlying the differential HSC key properties. Particularly, we identified GRNs and key regulators controlling lymphoid potentiality, self-renewal as well as aerobic respiration in human HSCs. Introducing selected regulators promotes key HSC functions in HSPCs derived from human pluripotent stem cells. Therefore, GRNs underlying key intrinsic properties of human HSCs provide a valuable guide to generate fully functional HSCs in vitro.

Composite ADRC Speed Control Method Based on LTDRO Feedforward Compensation.

The performance of the extended state observer (ESO) in an Active Disturbance Rejection Control (ADRC) is limited by the operational load in stepper motor control, which has high real-time requirements and may cause delays. Additionally, the complexity of parameter tuning, especially in high-order systems, further limits the ESO's performance. This paper proposes a composite ADRC (LTDRO-ADRC) based on a load torque dimensionality reduction observer (LTDRO). Firstly, the LTDRO is designed to estimate abrupt load disturbances that are difficult to compensate for using the ESO. Secondly, the transfer function under the double-closed loop is deduced. Additionally, the LTDRO uses a magnetic encoder to gather the system state and calculate the load torque. It then outputs a compensating current feedforward to the current loop input. This method reduces the delay and complexity of the ESO, improving the response speed of the ADRC speed ring and the overall response of the system to load changes. Simulation and experimental results demonstrate that it significantly enhances dynamic control performance and steady-state errors. LTDRO-ADRC can stabilize the speed again within 49 ms and 17 ms, respectively, in the face of sudden load increase and sudden load removal. At the same time, in terms of steady-state error, compared with ADRC and CADRC, they have increased by 94% and 88%, respectively. In terms of zero-speed starting motors, the response speed is increased by 58% compared to a traditional ADRC.

The Heptazine-Based Materials through Intrinsically Modification for the Cycloaddition of CO2 and Bisepoxides.

For the efficient utilization of CO2 into valuable product, the attractive carbon nitride catalysts have been widely studied. In this work, heptazine-related materials with varying degree of polymerization were designed by an intrinsically modification strategy and employed in the cycloaddition of CO2 with the bisepoxide 1, 4-butanediol diglycidyl ether (BDODGE). We initially figured out that the sample prepared at 450 °C contained more melem hydrate, exhibiting the best performance. The epoxides conversion and corresponding cyclic carbonates selectivity could achieve 93.1 % and 99.3 % at 140 °C for 20 h without any cocatalyst and solvent, respectively. Results of the catalytic tests suggested that the high catalytic activity was dependent on big size porous structure and the synergetic effect of active amino groups and -OH groups. The role of water in maintaining the specific structure and providing active site has been proved. Moreover, the CN-450-W catalyst exhibited outstanding recycling stability. And finally, a plausible reaction mechanism was proposed.

Discovery of a Novel CSF-1R Inhibitor with Highly Improved Pharmacokinetic Profiles and Superior Efficacy in Colorectal Cancer Immunotherapy.

Blocking CSF-1/CSF-1R pathway has emerged as a promising strategy to remodel tumor immune microenvironment (TME) by reprogramming tumor-associated macrophages (TAMs). In this work, a novel CSF-1R inhibitor C19 with a highly improved pharmacokinetic profile and in vivo anticolorectal cancer (CRC) efficiency was successfully discovered. C19 could effectively reprogram M2-like TAMs to M1 phenotype and reshape the TME by inducing the recruitment of CD8+ T cells into tumors and reducing the infiltration of immunosuppressive Tregs/MDSCs. Deeper mechanistic studies revealed that C19 facilitated the infiltration of CD8+ T cells by enhancing the secretion of chemokine CXCL9, thus significantly potentiating the anti-CRC efficiency of PD-1 blockade. More importantly, C19 combined with PD-1 mAb could induce durable antitumor immune memory, effectively overcoming the recurrence of CRC. Taken together, our findings suggest that C19 is a promising therapeutic option for sensitizing CRC to anti-PD-1 therapy.

Associations between waist circumference and nocturia in adults: National health and nutrition examination survey 2005-2020.

BACKGROUND: The relationship between waist circumference and nocturia has not been previously studied. This study investigated the association between waist circumference and the occurrence of nocturia in adults. METHODS: We analyzed data from the National Health and Nutrition Examination Survey covering 2005-2020, encompassing 6287 adults aged ≥20. Nocturia was defined as the need to urinate two or more times during the night. First, we compared baseline characteristics between the nocturia and non-nocturia groups. Subsequently, we used multivariate logistic regression analysis to investigate the relationship between waist circumference and nocturia prevalence. We also employed restricted cubic spline analysis to study the potential nonlinear correlation between waist circumference and the prevalence of nocturia. Recognizing the baseline data's heterogeneity based on nocturia prevalence, we conducted subgroup analyses according to age, sex, body mass index (BMI), and ethnicity. RESULTS: Our findings indicated that females, individuals aged ≥50, citizens, Non-Hispanic Black, those with lower education levels (high school or less), higher BMIs, lower family income-to-poverty ratios, higher waist circumference, hypertension, and diabetes were more likely to experience nocturia. Compared with individuals in the lowest waist circumference quartile (Q1), those in the higher quartiles (Q4) exhibited an increased risk of nocturia in Model 1 (Q4, OR:2.00, 95% CI:1.64, 2.45, p < 0.0001). These results remained consistent after adjusting for covariates in models 2 and 3. A restricted cubic spline analysis suggested a linear association between waist circumference and nocturia (P for nonlinearity = 0.066). Subgroup analyses based on age, sex, BMI, and ethnicity revealed no significant differences in the interaction tests between waist circumference and nocturia (P for interaction = 0.437, 0.331, 0.121, and 0.889, respectively), indicating that these baseline characteristics did not influence the association. CONCLUSIONS: Our findings indicated an association between increased waist circumference and a higher prevalence of nocturia. Knowledge of this association reinforces the importance of lifestyle modifications in maintaining a healthy waist circumference and informs public health strategies to address other potential risk factors for nocturia.

Examining the safety of mirabegron: an analysis of real-world pharmacovigilance data from the US FDA adverse event reporting system (FAERS) database.

Background: Mirabegron, the first ß-3 adrenergic receptor agonist, received approval from the Food and Drug Administration (FDA) in 2012 for the treatment of overactive bladder (OAB). This pharmacovigilance study investigated the safety profile of mirabegron treatment using the US FDA Adverse Event Reporting System (FAERS) database. Methods: This study employed disproportionality analyses, including the reporting odds ratio (ROR) and Bayesian Confidence Propagation Neural Network (BCPNN) algorithm, to quantify signals of adverse events associated with mirabegron. Results: From the first quarter of 2012 to the third quarter of 2023, a comprehensive total of 14,356,234 adverse event (AE) reports were submitted to the FDA Adverse Event Reporting System database. Within this dataset, encompassing 18,763 reports specifically associated with mirabegron, healthcare professionals notably contributed 2,902 of these reports. A total of 80 preferred terms (PTs) of interest were identified using both the ROR and information component algorithms. The most common AEs included blood pressure increased, urinary retention, atrial fibrillation, dry mouth, and tachycardia, which were consistent with the product instructions. Unexpected significant AEs, such as arrhythmia, palpitations, dementia, transient ischemic attack, Parkinson's disease, anti-neutrophil cytoplasmic antibody positive vasculitis, lip swelling, and swollen tongue, were also identified. The study findings indicated that the majority of onset time occurred within 30 days (n = 358, 55.68%). However, AEs were still possible after 1 year of mirabegron treatment. Conclusion: This study provided valuable evidence for the real-world safety of mirabegron, helping clinical professionals enhance their understanding of mirabegron's safety in clinical practice. It also contributed valuable evidence for further safety studies on mirabegron.

Enhancing prime editor flexibility with coiled-coil heterodimers.

BACKGROUND: Prime editing enables precise base substitutions, insertions, and deletions at targeted sites without the involvement of double-strand DNA breaks or exogenous donor DNA templates. However, the large size of prime editors (PEs) hampers their delivery in vivo via adeno-associated virus (AAV) due to the viral packaging limit. Previously reported split PE versions provide a size reduction, but they require intricate engineering and potentially compromise editing efficiency. RESULTS: Herein, we present a simplified split PE named as CC-PE, created through non-covalent recruitment of reverse transcriptase to the Cas9 nickase via coiled-coil heterodimers, which are widely used in protein design due to their modularity and well-understood sequence-structure relationship. We demonstrate that the CC-PE maintains or even surpasses the efficiency of unsplit PE in installing intended edits, with no increase in the levels of undesired byproducts within tested loci amongst a variety of cell types (HEK293T, A549, HCT116, and U2OS). Furthermore, coiled-coil heterodimers are used to engineer SpCas9-NG-PE and SpRY-PE, two Cas9 variants with more flexible editing scope. Similarly, the resulting NG-CC-PE and SpRY-CC-PE also achieve equivalent or enhanced efficiency of precise editing compared to the intact PE. When the dual AAV vectors carrying CC-PE are delivered into mice to target the Pcsk9 gene in the liver, CC-PE enables highly efficient precise editing, resulting in a significant reduction of plasma low-density lipoprotein cholesterol and total cholesterol. CONCLUSIONS: Our innovative, modular system enhances flexibility, thus potentially facilitating the in vivo applicability of prime editing.

Facilely Modified Nickel-Based Hole Transporting Layers for Organic Solar Cells with 19.12% Efficiency and Enhanced Stability.

Hole transporting layers (HTLs), strategically positioned between electrode and light absorber, play a pivotal role in shaping charge extraction and transport in organic solar cells (OSCs). However, the commonly used poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) HTL, with its hygroscopic and acidic nature, undermines the operational durability of OSC devices. Herein, an environmentally friendly approach is developed utilizing nickel acetate tetrahydrate (NiAc·4H2O) and [2-(9H-carbazol-9-yl)ethyl] phosphonic acid (2PACz) as the NiAc·4H2O/2PACz HTL, aiming at overcoming the limitations posed by the conventional PEDOT:PSS one. Encouragingly, a remarkable power conversion efficiency (PCE) of 19.12% is obtained for the OSCs employing NiAc·4H2O/2PACz as the HTL, surpassing that of devices with the PEDOT:PSS HTL (17.59%), which is ranked among the highest ones of OSCs. This improvement is attributed to the appropriate work function, enhanced hole mobility, facilitated exciton dissociation efficiency, and lower recombination loss of NiAc·4H2O/2PACz-based devices. Furthermore, the NiAc·4H2O/2PACz-based OSCs exhibit superior operational stability compared to their PEDOT:PSS-based counterparts. Of significant note, the NiAc·4H2O/2PACz HTL demonstrates a broad generality, boosting the PCE of the PM6:PY-IT and PM6:Y6-based OSCs from 16.47% and 16.79% (with PEDOT:PSS-based analogs as HTLs) to 17.36% and 17.57%, respectively. These findings underscore the substantial potential of the NiAc·4H2O/2PACz HTL in advancing OSCs, offering improved performance and stability, thereby opening avenue for highly efficient and reliable solar energy harvesting technologies.

Discovery of a Novel Orally Bioavailable FLT3-PROTAC Degrader for Efficient Treatment of Acute Myeloid Leukemia and Overcoming Resistance of FLT3 Inhibitors.

Fms-like tyrosine receptor kinase 3 (FLT3) proteolysis-targeting chimeras (PROTACs) represent a promising approach to eliminate the resistance of FLT3 inhibitors. However, due to the poor druggability of PROTACs, the development of orally bioavailable FLT3-PROTACs faces great challenges. Herein, a novel orally bioavailable FLT3-ITD degrader A20 with excellent pharmacokinetic properties was discovered through reasonable design. A20 selectively inhibited the proliferation of FLT3-ITD mutant acute myeloid leukemia (AML) cells and potently induced FLT3-ITD degradation through the ubiquitin-proteasome system. Notably, oral administration of A20 resulted in complete tumor regression on subcutaneous AML xenograft models. Furthermore, on systemic AML xenograft models, A20 could completely eliminate the CD45+CD33+ human leukemic cells in murine and significantly prolonged the survival time of mice. Most importantly, A20 exerted significantly improved antiproliferative activity against drug-resistant AML cells compared to existing FLT3 inhibitors. These findings suggested that A20 could serve as a promising drug candidate for relapsed or refractory AML.

Effectiveness of mHealth App-Based Interventions for Increasing Physical Activity and Improving Physical Fitness in Children and Adolescents: Systematic Review and Meta-Analysis.

BACKGROUND: The COVID-19 pandemic has significantly reduced physical activity (PA) levels and increased sedentary behavior (SB), which can lead to worsening physical fitness (PF). Children and adolescents may benefit from mobile health (mHealth) apps to increase PA and improve PF. However, the effectiveness of mHealth app-based interventions and potential moderators in this population are not yet fully understood. OBJECTIVE: This study aims to review and analyze the effectiveness of mHealth app-based interventions in promoting PA and improving PF and identify potential moderators of the efficacy of mHealth app-based interventions in children and adolescents. METHODS: We searched for randomized controlled trials (RCTs) published in the PubMed, Web of Science, EBSCO, and Cochrane Library databases until December 25, 2023, to conduct this meta-analysis. We included articles with intervention groups that investigated the effects of mHealth-based apps on PA and PF among children and adolescents. Due to high heterogeneity, a meta-analysis was conducted using a random effects model. The Cochrane Risk of Bias Assessment Tool was used to evaluate the risk of bias. Subgroup analysis and meta-regression analyses were performed to identify potential influences impacting effect sizes. RESULTS: We included 28 RCTs with a total of 5643 participants. In general, the risk of bias of included studies was low. Our findings showed that mHealth app-based interventions significantly increased total PA (TPA; standardized mean difference [SMD] 0.29, 95% CI 0.13-0.45; P<.001), reduced SB (SMD -0.97, 95% CI -1.67 to -0.28; P=.006) and BMI (weighted mean difference -0.31 kg/m2, 95% CI -0.60 to -0.01 kg/m2; P=.12), and improved muscle strength (SMD 1.97, 95% CI 0.09-3.86; P=.04) and agility (SMD -0.35, 95% CI -0.61 to -0.10; P=.006). However, mHealth app-based interventions insignificantly affected moderate to vigorous PA (MVPA; SMD 0.11, 95% CI -0.04 to 0.25; P<.001), waist circumference (weighted mean difference 0.38 cm, 95% CI -1.28 to 2.04 cm; P=.65), muscular power (SMD 0.01, 95% CI -0.08 to 0.10; P=.81), cardiorespiratory fitness (SMD -0.20, 95% CI -0.45 to 0.05; P=.11), muscular endurance (SMD 0.47, 95% CI -0.08 to 1.02; P=.10), and flexibility (SMD 0.09, 95% CI -0.23 to 0.41; P=.58). Subgroup analyses and meta-regression showed that intervention duration was associated with TPA and MVPA, and age and types of intervention was associated with BMI. CONCLUSIONS: Our meta-analysis suggests that mHealth app-based interventions may yield small-to-large beneficial effects on TPA, SB, BMI, agility, and muscle strength in children and adolescents. Furthermore, age and intervention duration may correlate with the higher effectiveness of mHealth app-based interventions. However, due to the limited number and quality of included studies, the aforementioned conclusions require validation through additional high-quality research. TRIAL REGISTRATION: PROSPERO CRD42023426532; https://tinyurl.com/25jm4kmf.

CSF1R inhibition reprograms tumor-associated macrophages to potentiate anti-PD-1 therapy efficacy against colorectal cancer.

PD-1 blockade therapy has made great breakthroughs in treatment of multiple solid tumors. However, patients with microsatellite-stable (MSS) colorectal cancer (CRC) respond poorly to anti-PD-1 immunotherapy. Although CRC patients with microstatellite instability (MSI) or microsatellite instability-high (MSI-H) can benefit from PD-1 blockade therapy, there are still some problems such as tumor recurrence. Tumor-associated macrophages (TAMs), most abundant immune components in tumor microenvironment (TME), largely limit the therapeutic efficacy of anti-PD-1 against CRC. The CSF1/CSF1R pathway plays a key role in regulating macrophage polarization, and blocking CSF1R signaling transduction may be a potential strategy to effectively reprogram macrophages and remodel TME. Here, we found that increasing expression of CSF1R in macrophages predicted poor prognosis in CRC cohort. Furthermore, we discovered a novel potent CSF1R inhibitor, PXB17, which significantly reprogramed M2 macrophages to M1 phenotype. Mechanically, PXB17 significantly blocked activation of PI3K/AKT/mTORC1 signaling, resulting in inhibition of cholesterol biosynthesis. Results from 3D co-culture system suggested that PXB17-repolarized macrophages could induce infiltration of CD8+ T lymphocytes in tumors and improve the immunosuppressive microenvironment. In vivo, PXB17 significantly halted CRC growth, with a stronger effect than PLX3397. In particular, PXB17 potently enhanced therapeutic activity of PD-1 mAb in CT-26 (MSS) model and prevented tumor recurrence in MC-38 (MSI-H) model by promoting formation of long-term memory immunity. Our study opens a new avenue for CSF1R in tumor innate and adaptive anti-tumor immunomodulatory activity and suggests that PXB17 is a promising immunotherapy molecule for enhancing the efficacy of PD-1 mAb or reducing tumor recurrence of CRC.

Multiple Congenital Granular Cell Epulis Involving Different Parts of the Oral Cavity: A Case Report.

Congenital granular cell epulis (CGCE) is a rare disease, particularly when it affects multiple oral and maxillofacial regions. We present the case of a female neonate with 4 asymptomatic masses attached to the maxillary and mandibular gingiva as well as the tongue. Due to the size of the masses causing feeding and respiratory difficulties, lesion removal was performed under general anesthesia. Histopathological analysis revealed tightly arranged polygonal cells with abundant granular eosinophilic cytoplasm. Immunohistochemically, the cells were negative for Smur100 (S-100), neuron-specific enolase (NSE), cluster of differentiation (CD) 68, and Sry-related HMG box (SOX)-10, and positive for alpha-1-antitrypsin (AAT) and vimentin. The diagnosis of multiple CGCEs was established through clinical examinations, histomorphometrical, and immunohistochemical analyses. In conclusion, CGCE should be considered in the differential diagnosis of intraoral lesions in neonates.

Engineered Luminescent Oncolytic Vaccinia Virus Activation of Photodynamic-Immune Combination Therapy for Colorectal Cancer.

Oncolytic virus therapy is currently regarded as a promising approach in cancer immunotherapy. It has greater therapeutic advantages for colorectal cancer that is prone to distant metastasis. However, the therapeutic efficacy and clinical application of viral agents alone for colorectal cancer remain suboptimal. In this study, an engineered oncolytic vaccinia virus (OVV-Luc) that expresses the firefly luciferase gene is developed and loaded Chlorin e6 (Ce6) onto the virus surface through covalent coupling, resulting in OVV-Luc@Ce6 (OV@C). The OV@C infiltrates tumor tissue and induces endogenous luminescence through substrate catalysis, resulting in the production of reactive oxygen species. This unique system eliminates the need for an external light source, making it suitable for photodynamic therapy (PDT) in deep tissues. Moreover, this synergistic effect between PDT and viral immunotherapy enhances dendritic cell maturation, macrophage polarization, and reversal of the immunosuppressive microenvironment. This synergistic effect has the potential to convert a "cold" into a "hot" tumor, it offers valuable insights for clinical translation and application.

A novel HDAC6 inhibitor attenuate APAP-induced liver injury by regulating MDH1-mediated oxidative stress.

Glutathione (GSH) depletion, mitochondrial damage, and oxidative stress have been implicated in the pathogenesis of acetaminophen (APAP) hepatotoxicity. Here, we demonstrated that the expression of histone deacetylase 6 (HDAC6) is highly elevated, whereas malate dehydrogenase 1 (MDH1) is downregulated in liver tissues and AML-12 cells induced by APAP. The therapeutic benefits of LT-630, a novel HDAC6 inhibitor on APAP-induced liver injury, were also substantiated. On this basis, we demonstrated that LT-630 improved the protein expression and acetylation level of MDH1. Furthermore, after overexpression of MDH1, an upregulated NADPH/NADP+ ratio and GSH level and decreased cell apoptosis were observed in APAP-stimulated AML-12 cells. Importantly, MDH1 siRNA clearly reversed the protection of LT-630 on APAP-stimulated AML-12 cells. In conclusion, LT-630 could ameliorate liver injury by modulating MDH1-mediated oxidative stress induced by APAP.

Interfacial π-p Electron Coupling Prompts Hydrogen Evolution Reaction Activity in Acidic Electrolyte.

The thermodynamically stable 2H-phase MoS2 is a brilliant material toward hydrogen evolution reaction (HER) owing to its excellent Gibbs free energy of hydrogen adsorption. Nevertheless, the poor intrinsic properties of 2H-MoS2 limit its electrocatalytic performances toward HER. In this work, graphitic carbon nitride covalently bridging 2H-MoS2 (MoS2/GCN) is proposed to construct robust HER electrocatalysts. The strong π-p electron coupling between the delocalized π electrons of GCN and the localized p electrons of S atoms sufficiently expose active sites and accelerate the reaction kinetics. To be specific, MoS2/GCN exhibits remarkable HER activity (160 mV at 10 mA·cm-2) and long-term durability. Importantly, MoS2/GCN also provides great potential for industrial application. Density functional theory (DFT) calculations disclose that the π-p electron coupling at the MoS2/GCN interface regulates the electronic structure of S atoms, consequently providing enhanced HER performance. This work presents a feasible pathway to develop advanced electrocatalysts for energy conversions.

Association between TV and/or video time and nocturia in adults: An analysis of the National Health and Nutrition Examination Survey.

AIMS: This study aimed to examine the correlation between television (TV) and/or video viewing time and the occurrence of nocturia in adults. METHODS: An analysis of data from the National Health and Nutrition Examination Survey for 2011-2016 was conducted, involving 13 294 adults aged 20 and older. The main outcome was specified as nocturia, which refers to the requirement of urinating two or more times during the night. Initially, baseline characteristics were contrasted between individuals with and without nocturia. The effects of TV and/or video viewing time on nocturia were further explored using multivariable logistic regression models. To acknowledge the variation in baseline data regarding the prevalence of nocturia, subgroup analyses were performed. RESULTS: Adjusted multivariate analysis revealed that individuals in the group with the longest TV and/or video viewing time had a significantly 48% higher risk of experiencing nocturia compared to those with the shortest TV and/or video viewing time. The results of subgroup analyses revealed no significant differences in the interaction tests between TV and/or video viewing time and nocturia. CONCLUSIONS: Our research showed that individuals who spent 5 or more hours a day watching TV and/or videos were significantly more likely to develop nocturia.