N6-Deoxyadenosine Methylation in Mammalian Mitochondrial DNA.

N6-Methyldeoxyadenosine (6mA) has recently been shown to exist and play regulatory roles in eukaryotic genomic DNA (gDNA). However, the biological functions of 6mA in mammals have yet to be adequately explored, largely due to its low abundance in most mammalian genomes. Here, we report that mammalian mitochondrial DNA (mtDNA) is enriched for 6mA. The level of 6mA in HepG2 mtDNA is at least 1,300-fold higher than that in gDNA under normal growth conditions, corresponding to approximately four 6mA modifications on each mtDNA molecule. METTL4, a putative mammalian methyltransferase, can mediate mtDNA 6mA methylation, which contributes to attenuated mtDNA transcription and a reduced mtDNA copy number. Mechanistically, the presence of 6mA could repress DNA binding and bending by mitochondrial transcription factor (TFAM). Under hypoxia, the 6mA level in mtDNA could be further elevated, suggesting regulatory roles for 6mA in mitochondrial stress response. Our study reveals DNA 6mA as a regulatory mark in mammalian mtDNA.

Epigenetic regulation of asymmetric cell division by the LIBR-BRD4 axis.

Asymmetric cell division (ACD) is a mechanism used by stem cells to maintain the number of progeny. However, the epigenetic mechanisms regulating ACD remain elusive. Here we show that BRD4, a BET domain protein that binds to acetylated histone, is segregated in daughter cells together with H3K56Ac and regulates ACD. ITGB1 is regulated by BRD4 to regulate ACD. A long noncoding RNA (lncRNA), LIBR (LncRNA Inhibiting BRD4), decreases the percentage of stem cells going through ACD through interacting with the BRD4 mRNAs. LIBR inhibits the translation of BRD4 through recruiting a translation repressor, RCK, and inhibiting the binding of BRD4 mRNAs to polysomes. These results identify the epigenetic regulatory modules (BRD4, lncRNA LIBR) that regulate ACD. The regulation of ACD by BRD4 suggests the therapeutic limitation of using BRD4 inhibitors to treat cancer due to the ability of these inhibitors to promote symmetric cell division that may lead to tumor progression and treatment resistance.

ß-Sitosterol suppresses hepatocellular carcinoma growth and metastasis via FOXM1-regulated Wnt/ß-catenin pathway.

ß-Sitosterol is a natural compound with demonstrated anti-cancer properties against various cancers. However, its effects on hepatocellular carcinoma (HCC) and the underlying mechanisms are not well understood. This study aims to investigate the impact of ß-sitosterol on HCC. In this study, we investigated the effects of ß-sitosterol on HCC tumour growth and metastasis using a xenograft mouse model and a range of molecular analyses, including bioinformatics, real-time PCR, western blotting, lentivirus transfection, CCK8, scratch and transwell assays. The results found that ß-sitosterol significantly inhibits HepG2 cell proliferation, migration and invasion both in vitro and in vivo. Bioinformatics analysis identifies forkhead box M1 (FOXM1) as a potential target for ß-sitosterol in HCC treatment. FOXM1 is upregulated in HCC tissues and cell lines, correlating with poor prognosis in patients. ß-Sitosterol downregulates FOXM1 expression in vitro and in vivo. FOXM1 overexpression mitigates ß-sitosterol's inhibitory effects on HepG2 cells. Additionally, ß-sitosterol suppresses epithelial-mesenchymal transition (EMT) in HepG2 cells, while FOXM1 overexpression promotes EMT. Mechanistically, ß-sitosterol inhibits Wnt/ß-catenin signalling by downregulating FOXM1, regulating target gene transcription related to HepG2 cell proliferation and metastasis. ß-Sitosterol shows promising potential as a therapeutic candidate for inhibiting HCC growth and metastasis through FOXM1 downregulation and Wnt/ß-catenin signalling inhibition.

Development of Shark Single Domain Antibodies Specific for Human α-Fetoprotein and the Multimerization Strategy in Serum Detection.

Sensitive detection of cancer biomarkers can contribute to the timely diagnosis and treatment of diseases. In this study, the whitespotted bamboo sharks were immunized with human α-fetoprotein (AFP), and a phage-displayed variable new antigen receptor (VNAR) single domain antibody library was constructed. Then four unique VNARs (VNAR1, VNAR11, VNAR21, and VNAR25) against AFP were isolated from the library by biopanning for the first time. All of the sequences belong to type II of VNAR, and the VNAR11 was much different from the rest of the three sequences. Then VNAR1 and VNAR11 were selected to fuse with the C4-binding protein α chain (C4bpα) sequence and efficiently expressed in the Escherichia coli system. Furthermore, a VNAR-C4bpα-mediated sandwich chemiluminescence immunoassay (VSCLIA) was developed for the detection of AFP in human serum samples. After optimization, the VSCLIA showed a limit of detection of 0.74 ng/mL with good selectivity and accuracy. Moreover, the results of clinical serum samples detected by the VSCLIA were confirmed by an automatic immunoanalyzer in the hospital, indicating its practical application in actual samples. In conclusion, the novel antibody element VNAR exhibits great potential for immunodiagnosis, and this study also provides a new direction and experimental basis for AFP detection.

In Situ Laser-Induced Breakdown Spectroscopy for Chromium Speciation Analysis Based on the Interactions of Oxygen-Containing Groups with Functionalized Co3O4-rGO: Evidence from Advanced Optical Techniques and Density Functional Theoretical Calculations under Electric Field.

Achieving accurate detection of different speciations of heavy metal ions (HMIs) in an aqueous solution is an urgent problem due to the different bioavailabilities and physiological toxicity. Herein, we nominated a novel strategy to detect HCrO4- and Cr(OH)2+ at a trace level via the electrochemical sensitive surface constructed by Co3O4-rGO modified with amino and carboxyl groups, which revealed that the interactions between distinct functional groups and different oxygen-containing groups of target ions are conducive to the susceptible and anti-interference detection. The detection sensitivities of 19.46 counts µg-1 L for HCrO4- and 13.44 counts µg-1 L for Cr(OH)2+ were obtained under optimal conditions, while the limits of detection were 0.10 and 0.12 µg L-1, respectively. Satisfactory anti-interference and actual water sample analysis results were obtained. A series of advanced optical techniques like X-ray photoelectron spectroscopy, X-ray absorption near-edge structure technology, and density functional theory calculations under an electric field demonstrated that chemical interactions between groups contribute more to the fixation of target ions than electrical attraction alone. The presence of oxygen-containing groups distinct from simple ionic forms was a critical factor in the selectivity and anti-interference detection. Furthermore, the valence cycle of Co(II)/(III) synergistically boosted the detection performance. This research provides a promising tactic from the microscopic perspective of groups' interactions to accomplish the precise speciation analysis of HMIs in the water environment.

Highly Stable Solid Contact Calcium Ion-Selective Electrodes: Rapid Ion-Electron Transduction Triggered by Lipophilic Anions Participating in Redox Reactions of CunS Nanoflowers.

Solid contact (SC) calcium ion-selective electrodes (Ca2+-ISEs) have been widely applied in the analysis of water quality and body fluids by virtue of the unique advantages of easy operation and rapid response. However, the potential drift during the long-term stability test hinders their further practical applications. Designing novel redox SC layers with large capacitance and high hydrophobicity is a promising approach to stabilize the potential stability, meanwhile, exploring the transduction mechanism is also of great guiding significance for the precise design of SC layer materials. Herein, flower-like copper sulfide (CunS-50) composed of nanosheets is meticulously designed as the redox SC layer by modification with the surfactant (CTAB). The CunS-50-based Ca2+-ISE (CunS-50/Ca2+-ISE) demonstrates a near-Nernstian slope of 28.23 mV/dec for Ca2+ in a wide activity linear range of 10-7 to 10-1 M, with a low detection limit of 3.16 × 10-8 M. CunS-50/Ca2+-ISE possesses an extremely low potential drift of only 1.23 ± 0.13 µV/h in the long-term potential stability test. Notably, X-ray absorption fine-structure (XAFS) spectra and electrochemical experiments are adopted to elucidate the transduction mechanism that the lipophilic anion (TFPB-) participates in the redox reaction of CunS-50 at the solid-solid interface of ion-selective membrane (ISM) and redox inorganic SC layer (CunS-50), thereby promoting the generation of free electrons to accelerate ion-electron transduction. This work provides an in-depth comprehension of the transduction mechanism of the potentiometric response and an effective strategy for designing redox materials of ion-electron transduction triggered by lipophilic anions.

Highly Accurate Determination of the Total Amount of Pb2+ and Pb(OH)+ in a Natural Water Environment Revealed by Dynamic Simulation and DFT Calculation: Benefit from the Electron Inverse Effect of Pt Nanoclusters over Defective g-C3N4.

Although utilizing nanomaterial-modified electrodes for lead ion detection has achieved great success, most of them are carried out under acidic conditions and ignore the variation of Pb(II) speciation at different pH conditions, leading to the potential inaccuracy of Pb(II) detection in a neutral natural water environment. Thus, designing a novel catalyst with high accuracy for the detection of various forms of the total amount of Pb(II) (Pb2+ and Pb(OH)+) in neutral waters is significant. Herein, Pt nanoclusters (Pt NCs) were elaborately constructed and stabilized on the Co single-atom-doped g-C3N4 with abundant N vacancies (Pt NCs/VN-C3N4), which achieved the ultrasensitive detection (102.16 µM µA-1) of Pb(II) in neutral conditions. The dynamic simulation and theoretical calculations reveal that the parallel deposition of Pb2+ and Pb(OH)+ occurs on the electrode surface modified by Pt NCs/VN-C3N4, and the current peaks of Pb(II) are cocontributed by Pb2+ and Pb(OH)+ species. An "electron inverse" phenomenon in Pt NCs/VN-C3N4 from the VN-C3N4 substrate to Pt NCs endows Pt NCs in an electron-rich state, serving as active centers to promote rapid and efficient reduction for both Pb2+ and Pb(OH)+, facilitating the accurate detection of the total amount of Pb(II) in all forms in the actual water environment.

Effects of dietary chitosan oligosaccharide on the growth, intestinal microbiota and immunity of juvenile red claw crayfish (Cherax quadricarinatus).

This study aimed to evaluate the potential benefits of chitosan oligosaccharide (COS) on red claw crayfish (Cherax quadricarinatus) and explore its underlying mechanisms. The crayfish were randomly divided into six groups, and the diets were supplemented with COS at levels of 0 (C0), 0.2 (C1), 0.4 (C2), 0.6 (C3), 0.8 (C4), and 1 (C5) g kg-1. Treatment with COS significantly improved the growth performance of the crayfish with a higher weight gain rate (WGR) and specific growth rate (SGR) in the C2 group compared to the C0 group. Additionally, the content of crude protein in the crayfish muscles in the C1 group was significantly higher than that of the C0 group. Regarding non-specific immunity, the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and alkaline phosphatase (AKP), and the levels of expression of the genes related to immunity (SOD; anti-lipopolysaccharide factor [ALF]; thioredoxin1 [Trx1]; C-type lysozyme, [C-LZM]; and GSH-Px) in the hepatopancreas and hemolymph increased significantly (P < 0.05) after supplementation with 0.4 g kg-1 of COS, while the content of malondialdehyde (MDA) decreased (P < 0.05). The survival rate of C. quadricarinatus increased (P < 0.05) in the C2, C3, C4, and C5 groups after the challenge with Aeromonas hydrophila. This study found that COS has the potential to modulate the composition of the intestinal microbiota and significantly reduce the abundance of species of the phylum Proteobacteria and the genera Aeromonas and Vibrio in the gut of C. quadricarinatus, while the abundance of bacteria in the phylum Firmicutes and the genus Candidatus_Hepatoplasma improved significantly. This study suggests that the inclusion of COS in the diet of C. quadricarinatus can enhance growth, boost immunity, and increase resistance to infection with A. hydrophila, especially when supplemented at 0.4-0.8 g kg-1.

Effects of dietary astaxanthin on growth performance, muscle composition, non-specific immunity, gene expression, and ammonia resistance of juvenile ivory shell (Babylonia areolate).

Astaxanthin is one of the important immunopotentators in aquaculture. However, little is known about the physiological changes and stress resistance effects of astaxanthin in marine gastropods. In this study, the effects of different astaxanthin concentrations (0, 25, 50, 75, and 100 mg/kg) on the growth, muscle composition, immune function, and resistance to ammonia stress in Babylonia areolata were investigated after three months of rearing. With the increase in astaxanthin content, the weight gain rate (WGR), specific growth rate (SGR), and survival rate (SR) of B. areolata showed an increasing trend. The 75-100 mg/kg group was significantly higher than the control group (0 mg/kg). There was no significant difference in the flesh shell ratio (FSR), viscerosomatic index (VSI), and soft tissue index (STI) of the experimental groups. Astaxanthin (75 mg/kg) significantly increased muscle crude protein content and increased hepatopancreas alkaline phosphatase (AKP), superoxide dismutase (SOD), and catalase (CAT) activity. Astaxanthin (75-100 mg/kg) significantly increased the total antioxidant capacity (T-AOC) and acid phosphatase (ACP) of the hepatopancreas and decreased the malondialdehyde (MDA) content of B. areolata. Astaxanthin significantly induced the expression levels of functional genes, such as SOD, Cu/ZnSOD, ferritin, ACP, and CYC in hepatopancreas and increased the survival rate of B. areolata under ammonia stress. The addition of 75-100 mg/kg astaxanthin to the feed improved the growth performance, muscle composition, immune function, and resistance to ammonia stress of B. areolata.

Effects of antimicrobial peptides from dietary Hermetia illucens larvae on the growth, immunity, gene expression, intestinal microbiota and resistance to Aeromonas hydrophila of juvenile red claw crayfish (Cherax quadricarinatus).

Antimicrobial peptides (AMPs), which are widely present in animals and plants, have a broad distribution, strong broad-spectrum antibacterial activity, low likelihood of developing drug resistance, high thermal stability and antiviral properties. The present study investigated the effects of adding AMPs from Hermetia illucens larvae on the growth performance, muscle composition, antioxidant capacity, immune response, gene expression, antibacterial ability and intestinal microbiota of Cherax quadricarinatus (red claw crayfish). Five experimental diets were prepared by adding 50 (M1), 100 (M2), 150 (M3) and 200 (M4) mg/kg of crude AMP extract from H. illucens larvae to the basal diet feed, which was also used as the control (M0). After an eight-week feeding experiment, it was discovered that the addition of 100-150 mg/kg of H. illucens larvae AMPs to the feed significantly improved the weight gain rate and specific growth rate of C. quadricarinatus. Furthermore, the addition of H. illucens larvae AMPs to the feed had no significant effect on the moisture content, crude protein, crude fat and ash content of the C. quadricarinatus muscle. The addition of 100-150 mg/kg of H. illucens larvae AMPs in the feed also increased the antioxidant capacity, nonspecific immune enzyme activity and related gene expression levels in C. quadricarinatus, thereby enhancing their antioxidant capacity and immune function. The H. illucens larvae AMPs improved the structure and composition of the intestinal microbiota of C. quadricarinatus, increasing the microbial community diversity of the crayfish gut. Finally, the addition of 100-150 mg/kg of H. illucens larvae AMPs in the feed enhanced the resistance of C. quadricarinatus against Aeromonas hydrophila, improving the survival rate of the crayfish. Based on the aforementioned findings, it is recommended that H. illucens larvae AMPs be incorporated into the C. quadricarinatus feed at a concentration of 100-150 mg/kg.

Associations between hollow viscus injury and acute kidney injury in blunt abdominal trauma: A national trauma data bank analysis.

PURPOSE: It is well established that hollow viscus perforation leads to sepsis and acute kidney injury (AKI) in non-trauma patients. However, the relationship between traumatic hollow viscus injury (HVI) and AKI is not well understood. Utilizing data from the National Trauma Data Bank, we investigated whether HVI serves as a risk factor for AKI. Additionally, we examined the characteristics of AKI in stable patients who underwent conservative treatment. METHODS: We reviewed blunt abdominal trauma (BAT) cases from 2012 to 2015, comparing patients with and without AKI. Significant factors from univariate analysis were tested in a multivariate logistic regression (MLR) to identify independent AKI determinants. We also analyzed subsets: patients without HVI and stable patients given conservative management. RESULTS: Out of the 563,040 BAT patients analyzed, 9073 (1.6%) developed AKI. While a greater proportion of AKI patients had HVI than those without AKI (13.3% vs. 5.2%, p < 0.001), this difference wasn't statistically significant in the MLR (p = 0.125). Notably, the need for laparotomy (odds = 3.108, p < 0.001) and sepsis (odds = 13.220, p < 0.001) were identified as independent risk factors for AKI. For BAT patients managed conservatively (systolic blood pressure >90 mmHg, without HVI or laparotomy; N = 497,066), the presence of sepsis was a significant predictor for the development of AKI (odds = 16.914, p < 0.001). CONCLUSIONS: While HVI wasn't a significant risk factor for AKI in BAT patients, the need for laparotomy was. Stable BAT patients managed conservatively are still at risk for AKI due to non-peritonitis related sepsis.

The expression profiles of cyp19a1, sf-1, esrs and gths in the brain-pituitary during gonadal sex differentiation in juvenile Japanese eels.

Eels are gonochoristic species whose gonadal differentiation initiates at the yellow eel stage and is influenced by environmental factors. We revealed some sex-related genes were sex dimorphically expressed in gonads during gonadal sex differentiation of Japanese eel (Anguilla japonica); however, the expression of sex-related genes in the brain-pituitary during gonadal sex differentiation in eels is still unclear. This study aimed to investigate the sex-related gene expressions in the brain-pituitary and tried to clarify their roles in the brain and gonads during gonadal sex differentiation. Based on our previous histological study, the control eels developed as males, and estradiol-17ß (E2) was used for feminization. Our results showed that during testicular differentiation, the brain cyp19a1 transcripts and aromatase proteins were increased significantly; moreover, the cyp19a1, sf-1, foxl2s, and esrs (except gperb) transcripts in the midbrain/pituitary also were increased significantly. Forebrain gnrh1 transcripts increased slightly during gonadal differentiation of both sexes, but the gnrhr1b and gnrhr2 transcripts in the midbrain/pituitary were stable during gonadal differentiation. The expression levels of gths and gh in the midbrain/pituitary were significantly increased during testicular differentiation and were much higher in males than in E2-feminized females. These results implied that endogenous estrogens might play essential roles in the brain/pituitary during testicular differentiation, sf-1, foxl2s, and esrs may have roles in cyp19a1 regulation in the midbrain/pituitary of Japanese eels. For the GnRH-GTH axis, gths, especially fshb, may be regulated by esrs and involved in regulating testicular differentiation and development in Japanese eels.

Evaluation of Concomitant Facial Fracture in Traumatic Brain Injury Patients-Simplification and External Validation of a Prediction Model.

BACKGROUND: Patients with traumatic brain injuries (TBIs) often experience concurrent facial bone fractures. In 2021, a prediction model with 10 variables was published and precisely predicted concomitant facial fractures in TBI patients. Herein, external validation and simplification of this model was performed. METHODS: Traumatic brain injury patients treated at a major referral trauma center were retrospectively reviewed for 1 year. The original prediction model (published in 2021), which was developed from a rural level II trauma center, was applied for external validation. A new and simplified model from our level I trauma center was developed and backwardly validated by rural level II trauma center data. RESULTS: In total, 313 TBI patients were enrolled; 101 (32.3%) had concomitant facial fractures. When the previous prediction model was applied to the validation cohort, it achieved acceptable discrimination, with an area under the receiver operating characteristic curve (AUC) of 0.713 and good precision, with a Brier score of 0.083. A new and simplified model with 6 variables (age, tooth rupture, epistaxis, facial lesion, eye injury, and intracranial hemorrhage) was created with excellent discrimination (AUC = 0.836) and good precision (Brier score of 0.055). The backward validation of this new model also showed excellent discrimination in the cohort used to develop the original model (AUC = 0.875). CONCLUSION: The original model provides an acceptable and reproducible prediction of concomitant facial fractures among TBI patients. A simplified model with fewer variables and the same accuracy could be applied in the emergency department and at higher- and lower-level trauma centers.

Hearing aid wear time and its impact on vocabulary in preschoolers with moderately severe to profound hearing loss.

OBJECTIVE: This study aimed to explore how the consistency of hearing aid (HA) use impacts vocabulary performance in children with moderately severe to profound hearing loss and determine the amount of HA use time associated with better vocabulary outcomes. DESIGN: Personal wear time percentage (WTP) was an indicator of HA use consistency, and the information on HA wear time was collected from both parent reports and datalogs. Pearson's correlations were performed to investigate the associations between hearing loss severity, WTP and vocabulary performance. Standard vocabulary scores among children below and above three WTP cutoff values (80%, 85%, and 90%) were examined to determine the WTP amount that yielded significantly better vocabulary outcomes. STUDY SAMPLE: Forty-seven children aged 36-79 months and their caregivers. RESULTS: Both parent reports and datalogs WTP significantly correlated with vocabulary outcomes. Parent-reported WTP were found to be predictive of datalogs WTP. Apart from hearing thresholds, HA fitting age and maternal education level, datalogs WTP was a significant independent predictor of vocabulary performance. Children with ≥ 90% WTP were more likely to perform better on vocabulary tests than those with < 90% WTP. CONCLUSION: The findings support the potential benefits of consistent HA use for vocabulary development.

Effect of sample length on MLU in Mandarin-speaking hard-of-hearing children.

This study investigated the impact of language sample length on mean length of utterance (MLU) and aimed to determine the minimum number of utterances required for a reliable MLU. Conversations were collected from Mandarin-speaking, hard-of-hearing and typical-hearing children aged 16-81 months. The MLUs were calculated using sample sizes ranging from 25 to 200 utterances. The results showed that for an MLU between 1.0 and 2.5, 25 and 50 utterances were sufficient for reliable MLU calculations for hard-of-hearing and typical-hearing children, respectively. For an MLU between 2.5 and 3.75, 125 utterances were required for both groups. For an MLU greater than 3.75, 150 and 125 utterances were required for hard-of-hearing and typical-hearing children, respectively. These findings suggest that a greater number of utterances are required for a reliable MLU as language complexity increases. Professionals working with hard-of-hearing children should consider collecting different numbers of utterances based on the children's language complexity levels.

Cross-modal digit span and vocabulary proficiency in deaf or hard-of-hearing children.

This study aims to examine the relationship between vocabulary proficiency and short-term memory capacity in deaf or hard-of-hearing (DHH) children. We test the hypothesis that the relationship between vocabulary skills and digit span performance could be strengthened when the digit span task encompasses cross-modal integration processes. A group of DHH children performed two types of auditory digit span tasks. Furthermore, they participated in a standardized vocabulary proficiency test, comprising two subtests: Receptive Vocabulary and Expressive Vocabulary. The verbal digit span served as a significant predictor of Expressive Vocabulary among the DHH children. Simultaneously, the auditory-pointing digit span accounted for a substantial portion of performance variation in both Receptive and Expressive Vocabulary. After considering the impact of the duration of auditory-verbal intervention through regression models, likelihood ratio tests demonstrated that the auditory-pointing digit span persisted as a significant determinant of both receptive and expressive vocabulary skills. A positive influence of the intervention was also confirmed by the present results. This study provides evidence that memory span and the ability to integrate cross-modal information could serve as significant cognitive correlates of vocabulary proficiency in DHH children.

Development of antiviral carbon quantum dots that target the Japanese encephalitis virus envelope protein.

Japanese encephalitis is a mosquito-borne disease caused by the Japanese encephalitis virus (JEV) that is prevalent in Asia and the Western Pacific. Currently, there is no effective treatment for Japanese encephalitis. Curcumin (Cur) is a compound extracted from the roots of Curcuma longa, and many studies have reported its antiviral and anti-inflammatory activities. However, the high cytotoxicity and very low solubility of Cur limit its biomedical applications. In this study, Cur carbon quantum dots (Cur-CQDs) were synthesized by mild pyrolysis-induced polymerization and carbonization, leading to higher water solubility and lower cytotoxicity, as well as superior antiviral activity against JEV infection. We found that Cur-CQDs effectively bound to the E protein of JEV, preventing viral entry into the host cells. In addition, after continued treatment of JEV with Cur-CQDs, a mutant strain of JEV was evolved that did not support binding of Cur-CQDs to the JEV envelope. Using transmission electron microscopy, biolayer interferometry, and molecular docking analysis, we revealed that the S123R and K312R mutations in the E protein play a key role in binding Cur-CQDs. The S123 and K312 residues are located in structural domains II and III of the E protein, respectively, and are responsible for binding to receptors on and fusing with the cell membrane. Taken together, our results suggest that the E protein of flaviviruses represents a potential target for the development of CQD-based inhibitors to prevent or treat viral infections.

Generalizable Descriptors of Highly Sensitive Detection of As(III) over Transition-Metal Single Atoms: A Combined Density Function Theory and Gradient Boosting Regression Approach.

Traditional nanomodified electrodes have made great achievements in electrochemical stripping voltammetry of sensing materials for As(III) detection. Moreover, the intermediate states are complicated to probe because of the ultrashort lifetime and complex reaction conditions of the electron transfer process in electroanalysis, which seriously hinder the identification of the actual active site. Herein, the intrinsic interaction of highly sensitive analytical behavior of nanomaterials is elucidated from the perspective of electronic structure through density functional theory (DFT) and gradient boosting regression (GBR). It is revealed that the atomic radius, d-band center (εd), and the largest coordinative TM-N bond length play a crucial role in regulating the arsenic reduction reaction (ARR) performance by the established ARR process for 27 sets of transition-metal single atoms supported on N-doped graphene. Furthermore, the database composed of filtered intrinsic electronic structural properties and the calculated descriptors of the central metal atom in TM-N4-Gra were also successfully extended to oxygen evolution reaction (OER) systems, which effectively verified the reliability of the whole approach. Generally, a multistep workflow is developed through GBR models combined with DFT for valid screening of sensing materials, which will effectively upgrade the traditional trial-and-error mode for electrochemical interface designing.

Practical Strategy for Arsenic(III) Electroanalysis without Modifier in Natural Water: Triggered by Iron Group Ions in Solution.

Significant progress has been made in nanomaterial-modified electrodes for highly efficient electroanalysis of arsenic(III) (As(III)). However, the modifiers prepared using some physical methods may easily fall off, and active sites are not uniform, causing the potential instability of the modified electrode. This work first reports a promising practical strategy without any modifiers via utilizing only soluble Fe3+ as a trigger to detect trace-level As(III) in natural water. This method reaches an actual detection limit of 1 ppb on bare glassy carbon electrodes and a sensitivity of 0.296 µA ppb-1 with excellent stability. Kinetic simulations and experimental evidence confirm the codeposition mechanism that Fe3+ is preferentially deposited as Fe0, which are active sites to adsorb As(III) and H+ on the electrode surface. This facilitates the formation of AsH3, which could further react with Fe2+ to produce more As0 and Fe0. Meanwhile, the produced Fe0 can also accelerate the efficient enrichment of As0. Remarkably, the proposed sensing mechanism is a general rule for the electroanalysis of As(III) that is triggered by iron group ions (Fe2+, Fe3+, Co2+, and Ni2+). The interference analysis of coexisting ions (Cu2+, Zn2+, Al3+, Hg2+, Cd2+, Pb2+, SO42-, NO3-, Cl-, and F-) indicates that only Cu2+, Pb2+, and F- showed inhibitory effects on As(III) due to the competition of active sites. Surprisingly, adding iron power effectively eliminates the interference of Cu2+ in natural water, achieving a higher sensitivity for 1-15 ppb As(III) (0.487 µA ppb-1). This study provides effective solutions to overcome the potential instability of modified electrodes and offers a practical sensing platform for analyzing other heavy-metal anions.

Interplay between lncRNA RP11-367G18.1 variant 2 and YY1 plays a vital role in hypoxia-mediated gene expression and tumorigenesis.

BACKGROUND: The hypoxia-responsive long non-coding RNA, RP11-367G18.1, has recently been reported to induce histone 4 lysine 16 acetylation (H4K16Ac) through its variant 2; however, the underlying molecular mechanism remains poorly understood. METHODS: RNA pull-down assay and liquid chromatography-tandem mass spectrometry were performed to identify RP11-367G18.1 variant 2-binding partner. The molecular events were examined utilizing western blot analysis, real-time PCR, luciferase reporter assay, chromatin immunoprecipitation, and chromatin isolation by RNA purification assays. The migration, invasion, soft agar colony formation, and in vivo xenograft experiments were conducted to evaluate the impact of RP11-367G18.1 variant 2-YY1 complex on tumor progression. RESULTS: In this study, RNA sequencing data revealed that hypoxia and RP11-367G18.1 variant 2 co-regulated genes were enriched in tumor-related pathways. YY1 was identified as an RP11-367G18.1 variant 2-binding partner that activates the H4K16Ac mark. YY1 was upregulated under hypoxic conditions and served as a target gene for hypoxia-inducible factor-1α. RP11-367G18.1 variant 2 colocalized with YY1 and H4K16Ac in the nucleus under hypoxic conditions. Head and neck cancer tissues had higher levels of RP11-367G18.1 and YY1 which were associated with poor patient outcomes. RP11-367G18.1 variant 2-YY1 complex contributes to hypoxia-induced epithelial-mesenchymal transition, cell migration, invasion, and tumorigenicity. YY1 regulated hypoxia-induced genes dependent on RP11-367G18.1 variant 2. CONCLUSIONS: RP11-367G18.1 variant 2-YY1 complex mediates the tumor-promoting effects of hypoxia, suggesting that this complex can be targeted as a novel therapeutic strategy for cancer treatment.