AAV-delivered suppressor tRNA overcomes a nonsense mutation in mice.

Gene therapy is a potentially curative medicine for many currently untreatable diseases, and recombinant adeno-associated virus (rAAV) is the most successful gene delivery vehicle for in vivo applications1-3. However, rAAV-based gene therapy suffers from several limitations, such as constrained DNA cargo size and toxicities caused by non-physiological expression of a transgene4-6. Here we show that rAAV delivery of a suppressor tRNA (rAAV.sup-tRNA) safely and efficiently rescued a genetic disease in a mouse model carrying a nonsense mutation, and effects lasted for more than 6 months after a single treatment. Mechanistically, this was achieved through a synergistic effect of premature stop codon readthrough and inhibition of nonsense-mediated mRNA decay. rAAV.sup-tRNA had a limited effect on global readthrough at normal stop codons and did not perturb endogenous tRNA homeostasis, as determined by ribosome profiling and tRNA sequencing, respectively. By optimizing the AAV capsid and the route of administration, therapeutic efficacy in various target tissues was achieved, including liver, heart, skeletal muscle and brain. This study demonstrates the feasibility of developing a toolbox of AAV-delivered nonsense suppressor tRNAs operating on premature termination codons (AAV-NoSTOP) to rescue pathogenic nonsense mutations and restore gene function under endogenous regulation. As nonsense mutations account for 11% of pathogenic mutations, AAV-NoSTOP can benefit a large number of patients. AAV-NoSTOP obviates the need to deliver a full-length protein-coding gene that may exceed the rAAV packaging limit, elicit adverse immune responses or cause transgene-related toxicities. It therefore represents a valuable addition to gene therapeutics.

Genetically Encoded Lizard Color Divergence for Camouflage and Thermoregulation.

Local adaptation is critical in speciation and evolution, yet comprehensive studies on proximate and ultimate causes of local adaptation are generally scarce. Here, we integrated field ecological experiments, genome sequencing, and genetic verification to demonstrate both driving forces and molecular mechanisms governing local adaptation of body coloration in a lizard from the Qinghai-Tibet Plateau. We found dark lizards from the cold meadow population had lower spectrum reflectance but higher melanin contents than light counterparts from the warm dune population. Additionally, the colorations of both dark and light lizards facilitated the camouflage and thermoregulation in their respective microhabitat simultaneously. More importantly, by genome resequencing analysis, we detected a novel mutation in Tyrp1 that underpinned this color adaptation. The allele frequencies at the site of SNP 459# in the gene of Tyrp1 are 22.22% G/C and 77.78% C/C in dark lizards and 100% G/G in light lizards. Model-predicted structure and catalytic activity showed that this mutation increased structure flexibility and catalytic activity in enzyme TYRP1, and thereby facilitated the generation of eumelanin in dark lizards. The function of the mutation in Tyrp1 was further verified by more melanin contents and darker coloration detected in the zebrafish injected with the genotype of Tyrp1 from dark lizards. Therefore, our study demonstrates that a novel mutation of a major melanin-generating gene underpins skin color variation co-selected by camouflage and thermoregulation in a lizard. The resulting strong selection may reinforce adaptive genetic divergence and enable the persistence of adjacent populations with distinct body coloration.

Inhibition of RhoGEF/RhoA alleviates regorafenib resistance and cancer stemness via Hippo signaling pathway in hepatocellular carcinoma.

Patients with hepatocellular carcinoma (HCC) are vulnerable to drug resistance. Although drug resistance has been taken much attention to HCC therapy, little is known of regorafenib and regorafenib resistance (RR). This study aimed to determine the drug resistance pattern and the role of RhoA in RR. Two regorafenib-resistant cell lines were constructed based on Huh7 and Hep3B cell lines. In vitro and in vivo assays were conducted to study RhoA expression, the activity of Hippo signaling pathway and cancer stem cell (CSC) traits. The data showed that RhoA was highly expressed, Hippo signaling was hypoactivated and CSC traits were more prominent in RR cells. Inhibiting RhoA could reverse RR, and the alliance of RhoA inhibition and regorafenib synergistically attenuated CSC phenotype. Furthermore, inhibiting LARG/RhoA increased Kibra/NF2 complex formation, prevented YAP from shuttling into the nucleus and repressed CD44 mRNA expression. Clinically, the high expression of RhoA correlated with poor prognosis. LARG, RhoA, YAP1 and CD44 show positive correlation with each other. Thus, inhibition of RhoGEF/RhoA has the potential to reverse RR and repress CSC phenotype in HCC.

The SphK1/S1P Axis Regulates Synaptic Vesicle Endocytosis via TRPC5 Channels.

Sphingosine-1-phosphate (S1P), a bioactive sphingolipid concentrated in the brain, is essential for normal brain functions, such as learning and memory and feeding behaviors. Sphingosine kinase 1 (SphK1), the primary kinase responsible for S1P production in the brain, is abundant within presynaptic terminals, indicating a potential role of the SphK1/S1P axis in presynaptic physiology. Altered S1P levels have been highlighted in many neurologic diseases with endocytic malfunctions. However, it remains unknown whether the SphK1/S1P axis may regulate synaptic vesicle endocytosis in neurons. The present study evaluates potential functions of the SphK1/S1P axis in synaptic vesicle endocytosis by determining effects of a dominant negative catalytically inactive SphK1. Our data for the first time identify a critical role of the SphK1/S1P axis in endocytosis in both neuroendocrine chromaffin cells and neurons from mice of both sexes. Furthermore, our Ca2+ imaging data indicate that the SphK1/S1P axis may be important for presynaptic Ca2+ increases during prolonged stimulations by regulating the Ca2+ permeable TRPC5 channels, which per se regulate synaptic vesicle endocytosis. Collectively, our data point out a critical role of the regulation of TRPC5 by the SphK1/S1P axis in synaptic vesicle endocytosis.SIGNIFICANCE STATEMENT Sphingosine kinase 1 (SphK1), the primary kinase responsible for brain sphingosine-1-phosphate (S1P) production, is abundant within presynaptic terminals. Altered SphK1/S1P metabolisms has been highlighted in many neurologic disorders with defective synaptic vesicle endocytosis. However, whether the SphK1/S1P axis may regulate synaptic vesicle endocytosis is unknown. Here, we identify that the SphK1/S1P axis regulates the kinetics of synaptic vesicle endocytosis in neurons, in addition to controlling fission-pore duration during single vesicle endocytosis in neuroendocrine chromaffin cells. The regulation of the SphK1/S1P axis in synaptic vesicle endocytosis is specific since it has a distinguished signaling pathway, which involves regulation of Ca2+ influx via TRPC5 channels. This discovery may provide novel mechanistic implications for the SphK1/S1P axis in brain functions under physiological and pathologic conditions.

Strong Metal-Support Interaction Modulation between Pt Nanoclusters and Mn3O4 Nanosheets through Oxygen Vacancy Control to Achieve High Activities for Acidic Hydrogen Evolution.

The optimization of metal-support interactions is used to fabricate noble metal-based nanoclusters with high activity for hydrogen evolution reaction (HER) in acid media. Specifically, the oxygen-defective Mn3O4 nanosheets supported Pt nanoclusters of ≈1.71 nm in diameter (Pt/V·-Mn3O4 NSs) are synthesized through the controlled solvothermal reaction. The Pt/V·-Mn3O4 NSs show a superior activity and excellent stability for the HER in the acidic media. They only require an overpotential of 19 mV to drive -10 mA cm-2 and show negligible activity loss at -10 and -250 mA cm-2 for >200 and >60 h, respectively. Their Pt mass activity is 12.4 times higher than that of the Pt/C and even higher than those of many single-atom based Pt catalysts. DFT calculations show that their high HER activity arises mainly from the strong metal-support interaction between Pt and Mn3O4. It can facilitate the charge transfer from Mn3O4 to Pt, optimizing the H adsorption on the catalyst surface and promoting the evolution of H2 through the Volmer-Tafel mechanism. The oxygen vacancies in the V·-Mn3O4 NSs are found to be inconducive to the high activity of the Pt/V·-Mn3O4 NSs, highlighting the great importance to reduce the vacancy levels in V·-Mn3O4 NSs.

Rational Design of Hollow Structural Materials for Sodium-Ion Battery Anodes.

The development of sodium-ion battery (SIB) anodes is still hindered by their rapid capacity decay and poor rate capabilities. Although there have been some new materials that can be used to fabricate stable anodes, SIBs are still far from wide applications. Strategies like nanostructure construction and material modification have been used to prepare more robust SIB anodes. Among all the design strategies, the hollow structure design is a promising method in the development of advanced anode materials. In the past decade, research efforts have been devoted to modifying the synthetic route, the type of templates, and the interior structure of hollow structures with high capacity and stability. A brief introduction is made to the main material systems and classifications of hollow structural materials first. Then different morphologies of hollow structural materials for SIB anodes from the latest reports are discussed, including nanoboxes, nanospheres, yolk shells, nanotubes, and other more complex shapes. The most used templates for the synthesis of hollow structrual materials are covered and the perspectives are highlighted at the end. This review offers a comprehensive discussion of the synthesis of hollow structural materials for SIB anodes, which could be potentially of use to research areas involving hollow materials design for batteries.

Amplifying hepatic L-aspartate levels suppresses CCl4-induced liver fibrosis by reversing glucocorticoid receptor ß-mediated mitochondrial malfunction.

Liver fibrosis is a determinant-stage process of many chronic liver diseases and affected over 7.9 billion populations worldwide with increasing demands of ideal therapeutic agents. Discovery of active molecules with anti-hepatic fibrosis efficacies presents the most attacking filed. Here, we revealed that hepatic L-aspartate levels were decreased in CCl4-induced fibrotic mice. Instead, supplementation of L-aspartate orally alleviated typical manifestations of liver injury and fibrosis. These therapeutic efficacies were alongside improvements of mitochondrial adaptive oxidation. Notably, treatment with L-aspartate rebalanced hepatic cholesterol-steroid metabolism and reduced the levels of liver-impairing metabolites, including corticosterone (CORT). Mechanistically, L-aspartate treatment efficiently reversed CORT-mediated glucocorticoid receptor ß (GRß) signaling activation and subsequent transcriptional suppression of the mitochondrial genome by directly binding to the mitochondrial genome. Knockout of GRß ameliorated corticosterone-mediated mitochondrial dysfunction and hepatocyte damage which also weakened the improvements of L-aspartate in suppressing GRß signaling. These data suggest that L-aspartate ameliorates hepatic fibrosis by suppressing GRß signaling via rebalancing cholesterol-steroid metabolism, would be an ideal candidate for clinical liver fibrosis treatment.

Predictive Value of Combined HbA1c and Neutrophil-to-Lymphocyte Ratio for Diabetic Peripheral Neuropathy in Type 2 Diabetes.

BACKGROUND Diabetic peripheral neuropathy (DPN) is a prevalent complication affecting over 60% of type 2 diabetes patients. Early diagnosis is challenging, leading to irreversible impacts on quality of life. This study explores the predictive value of combining HbA1c and Neutrophil-to-Lymphocyte Ratio (NLR) for early DPN detection. MATERIAL AND METHODS An observational study was conducted at the First People's Hospital of Linping District, Hangzhou spanning from May 2019 to July 2020. Data on sex, age, biochemical measurements were collected from electronic medical records and analyzed. Employing multivariate logistic regression analysis, we sought to comprehend the factors influencing the development of DPN. To assess the predictive value of individual and combined testing for DPN, a receiver operating characteristic (ROC) curve was plotted. The data analysis was executed using R software (Version: 4.1.0). RESULTS The univariate and multivariate logistic regression analysis identified the level of glycated hemoglobin (HbA1C) (OR=1.94, 95% CI: 1.27-3.14) and neutrophil-to-lymphocyte ratio (NLR) (OR=4.60, 95% CI: 1.15-22.62, P=0.04) as significant risk factors for the development of DPN. Receiver operating characteristic (ROC) curve analysis demonstrated that HbA1c, NLR, and their combined detection exhibited high sensitivity in predicting the development of DPN (71.60%, 90.00%, and 97.2%, respectively), with moderate specificity (63.8%, 45.00%, and 50.00%, respectively). The area under the curve (AUC) for these predictors was 0.703, 0.661, and 0.733, respectively. CONCLUSIONS HbA1c and NLR emerge as noteworthy risk indicators associated with the manifestation of DPN in patients with type 2 diabetes. The combined detection of HbA1c and NLR exhibits a heightened predictive value for the development of DPN.

Cholangiocarcinoma identified in perforated choledochal cyst in a 3-year-old boy.

Cholangiocarcinoma in patients with Choledochal cysts is rare in childhood; however, it seriously affects the prognosis of the disease. The key to addressing this situation lies in completely removing the extrahepatic cyst. We herein present a case report of a 3-year-old boy with cholangiocarcinoma associated with a choledochal cyst (CDC). Preoperative 3D simulation, based on CT data, played an important role in the treatment of this patient.

Age, growth, maturity and mortality of the tapetail anchovy Coilia brachygnathus (Engraulidae) in Lake Honghu, China.

The tapertail anchovy Coilia brachygnathus, a commercially important species mainly distributed along the mid-lower Chang-Jiang basin, is by far the most dominant species in Lake Honghu. To figure out its success in this semiclosed lake, some basic biological parameters of this anchovy were analysed based on samples seasonally collected from October 2020 to December 2021. The results demonstrated that the age classes of fished individuals varied from 0.5 to 3.5, with the majority (97.36%) being between 0.5 and 3 years old. The size at 50% maturity of 17.2 cm total length (TL) for females and 19.0 cm TL for males corresponded to 1 and 1.6 years, respectively. Coilia brachygnathus has a short life span, early sexual maturity and a relatively fast growth rate. The flourishing of the fish in the lake is mainly attributed to its short life span, early maturity, fast growth rate, closed fishing, pelagic spawners, the availability of plenty of food and low predation effect on it. Age 3.5 year occurs in an extremely small percentage of the total (<3%), indicating that a large number of larger-sized or older fish died after spawning, which is probably one of the major sources of water pollution if the closed fishing measure is adopted in Lake Honghu. Thus, individuals older than 2 years or more than 20.0 cm TL should be harvested. These findings have important management implications for the fish resources in Lake Honghu and beyond.

Modular Synthesis of Fully-Substituted and Configuration-Defined Alkyl Vinyl Ethers Enabled by Dual-Functional Copper Catalysis.

Here we present a modular, chemo-, regio-, and stereoselective synthesis of fully-substituted and configuration-defined alkyl vinyl ethers (AVEs) using simple chemical feedstocks. The distinctive approach involves the chemo- and regioselective functionalization of the CF2 unit in gem-difluorinated cyclopropanes with O-H and C-H nucleophiles in a specific order. The resulting highly functionalized cyclopropanyl ethers then undergo a stereoselective ring-opening process to produce fully-substituted and configuration-defined AVEs. These AVEs are rarely accessible through conventional methods and are easily transformable. Mechanistic experiments indicate that the success of this method relies on the use of dual-functional copper catalysis, which is involved in both the functionalization of the CF2 unit and the subsequent ring-opening process.

Rhodium-Catalyzed Enantio- and Regioselective Allylation of Indoles with gem-Difluorinated Cyclopropanes.

The use of gem-difluorinated cyclopropanes (gem-DFCPs) as fluoroallyl surrogates under transition-metal catalysis has drawn considerable attention recently but such reactions are restricted to producing achiral or racemic mono-fluoroalkenes. Herein, we report the first enantioselective allylation of indoles under rhodium catalysis with gem-DFCPs. This reaction shows exceptional branched regioselectivity towards rhodium catalysis with gem-DFCPs, which provides an efficient route to enantioenriched fluoroallylated indoles with wide substrate scope and good functional group tolerance.

Monitoring ROS Responsive Fe3O4-based Nanoparticle Mediated Ferroptosis and Immunotherapy via 129Xe MRI.

The immune checkpoint blockade strategy has improved the survival rate of late-stage lung cancer patients. However, the low immune response rate limits the immunotherapy efficiency. Here, we report a ROS-responsive Fe3O4-based nanoparticle that undergoes charge reversal and disassembly in the tumor microenvironment, enhancing the uptake of Fe3O4 by tumor cells and triggering a more severe ferroptosis. In the tumor microenvironment, the nanoparticle rapidly disassembles and releases the loaded GOx and the immune-activating peptide Tuftsin under overexpressed H2O2. GOx can consume the glucose of tumor cells and generate more H2O2, promoting the disassembly of the nanoparticle and drug release, thereby enhancing the therapeutic effect of ferroptosis. Combined with Tuftsin, it can more effectively reverse the immune-suppressive microenvironment and promote the recruitment of effector T cells in tumor tissues. Ultimately, in combination with α-PD-L1, there is significant inhibition of the growth of lung metastases. Additionally, the hyperpolarized 129Xe method has been used to evaluate the Fe3O4 nanoparticle-mediated immunotherapy, where the ventilation defects in lung metastases have been significantly improved with complete lung structure and function recovered. The ferroptosis-enhanced immunotherapy combined with non-radiation evaluation methodology paves a new way for designing novel theranostic agents for cancer therapy.

Plasma-Induced Formation of Pt Nanoparticles with Optimized Surface Oxidation States for Methanol Oxidation and Oxygen Reduction Reactions to Achieve High-Performance DMFCs.

Plasma treatment and reduction are used to synthesize Pt nanoparticles (NPs) on nitrogen-doped carbon nanotubes (p-Pt/p-NCNT) with a low Pt content. In particular, the plasma treatment is used to treat the NCNT to give it with more surface defects, facilitating a better growth of the Pt NPs, while the plasma reduction produces the Pt NPs with a reduced fraction of the surface atoms at the high oxidation states, increasing the catalytic activities of the p-Pt@p-NCNT. Even at the low Pt content (7.8 wt.%), the p-Pt@p-NCNT shows superior catalytic activities and good stabilities for methanol oxidation reaction (MOR) and oxygen reduction reaction (ORR). The density functional theory (DFT) calculations indicate that the defects generated in the plasma treatment can help the growth of the Pt NPs on the NCNTs, leading to the stronger electronic coupling between Pt and NCNT and the increased stability of the catalyst. The plasma reduction can give the Pt NPs with optimized surface oxidation states, decreasing the energy barriers of the rate-determining steps for MOR and ORR. When used as the anode and cathode catalysts for the direct methanol fuel cells (DMFCs), the p-Pt@p-NCNT exhibits a higher maximum power density of 81.9 mW cm-2  at 80 °C and shows good durability.

One-Pot Assembly of Dual-Site-Specific Antibody-Drug Conjugates via Glycan Remodeling and Affinity-Directed Traceless Conjugation.

The drug-to-antibody ratio (DAR) value and dual-drug combination greatly influence the therapeutic index of antibody-drug conjugates (ADCs). The reported approaches usually require multifunctional branched linkers, a combination of complicated technologies, or protein-protein ligation, which may incorporate multihydrophobic fragments or result in low coupling efficiency. Herein, we developed a facile and efficient one-pot method to assemble dual-site-specific ADCs with defined DARs at both the N-glycosylation site and K248 site, either with the same payloads or with two types of payloads. The constructed dual-site ADCs showed acceptable homogeneity, excellent buffer stability, and enhanced in vitro and in vivo efficiency.

Distinct responses and range shifts of lizard populations across an elevational gradient under climate change.

Ongoing climate change has profoundly affected global biodiversity, but its impacts on populations across elevations remain understudied. Using mechanistic niche models incorporating species traits, we predicted ecophysiological responses (activity times, oxygen consumption and evaporative water loss) for lizard populations at high-elevation (<3600 m asl) and extra-high-elevation (≥3600 m asl) under recent (1970-2000) and future (2081-2100) climates. Compared with their high-elevation counterparts, lizards from extra-high-elevation are predicted to experience a greater increase in activity time and oxygen consumption. By integrating these ecophysiological responses into hybrid species distribution models (HSDMs), we were able to make the following predictions under two warming scenarios (SSP1-2.6, SSP5-8.5). By 2081-2100, we predict that lizards at both high- and extra-high-elevation will shift upslope; lizards at extra-high-elevation will gain more and lose less habitat than will their high-elevation congeners. We therefore advocate the conservation of high-elevation species in the context of climate change, especially for those populations living close to their lower elevational range limits. In addition, by comparing the results from HSDMs and traditional species distribution models, we highlight the importance of considering intraspecific variation and local adaptation in physiological traits along elevational gradients when forecasting species' future distributions under climate change.

Activity and participation in haemophiliacs: Item response modelling based on international classification of functioning, disability and health.

BACKGROUND AND OBJECTIVES: There is scant research investigating the user-friendly functional assessment tool conceptualized by the International Classification of Functioning, Disability and Health (ICF) among persons with haemophilia (PWH). This study aims to accomplish two goals: (1) quantifying comprehensive functioning measures of haemophilia through Item Response Theory (IRT); (2) discussing patient-centred care based on the Wright map of personal ability and item difficulty. METHODS: A cross-sectional study was carried out in 70 PWH (mean age, 33.09 ± 11.04) via convenience sampling. All patients completed the 45 ICF categories of haemophilic-specific activity and participation. Psychometric properties of the categories were examined using Mokken scale analysis and parametric item response modelling. RESULTS: We extracted a unidimensional scale with 31 categories, and constructed a Rasch model with good fitness. The Cronbach's α of the scale was .9713, with the Guttman's λ2  = .9730, Molenaar Sijtsma ρ = .9802, and latent class reliability coefficient = .9769, indicating great internal reliability. The estimated individual social competence by the Rasch model was highly related to the index score of the three-level EuroQol five-dimensional questionnaire (EQ-5D-3L) (p < .001, r = .62), and had a moderate correlation (p < .001, r = .54) with the score of Haemophilia Activities List (HAL). CONCLUSIONS: The ICF scale of haemophilic activity and participation with 31 categories (HAPPY-ICF) has good construct validity and internal consistency. The person-item threshold distribution map might be helpful in research and clinical practices for patient-oriented care.

Divergent effects of climate change on the egg-laying opportunity of species in cold and warm regions.

Climate warming can substantially impact embryonic development and juvenile growth in oviparous species. Estimating the overall impacts of climate warming on oviparous reproduction is difficult because egg-laying events happen throughout the reproductive season. Successful egg laying requires the completion of embryonic development as well as hatching timing conducive to offspring survival and energy accumulation. We propose a new metric-egg-laying opportunity (EO)-to estimate the annual hours during which a clutch of freshly laid eggs yields surviving offspring that store sufficient energy for overwintering. We estimated the EO within the distribution of a model species, Sceloporus undulatus, under recent climate condition and a climate-warming scenario by combining microclimate data, developmental functions, and biophysical models. We predicted that EO will decline as the climate warms at 74.8% of 11,407 sites. Decreasing hatching success and offspring energy accounted for more lost EO hours (72.6% and 72.9%) than the occurrence of offspring heat stress (59.9%). Nesting deeper (at a depth of 12 cm) may be a more effective behavioral adjustment for retaining EO than using shadier (50% shade) nests because the former fully mitigated the decline of EO under the considered warming scenario at more sites (66.1%) than the latter (28.3%). We advocate for the use of EO in predicting the impacts of climate warming on oviparous animals because it encapsulates the integrative impacts of climate warming on all stages of reproductive life history.

Efectos divergentes del cambio climático sobre la oportunidad de desove de las especies en regiones cálidas y frías Resumen El calentamiento global puede tener un impacto considerable sobre el desarrollo embrionario y el crecimiento juvenil de las especies ovíparas. Es complicado estimar el impacto general que tiene el calentamiento global sobre la reproducción ovípara ya que los eventos de desove suceden durante la época reproductiva. El desove exitoso requiere que se complete el desarrollo embrionario y que el momento de eclosión sea favorable para la supervivencia de las crías y la acumulación de energía. Proponemos una nueva medida-oportunidad de desove (OD)-para estimar las horas anuales durante las cuales una puesta de huevos recién desovados produce crías que sobreviven y almacenan suficiente energía para invernar. Estimamos la OD dentro de un modelo de distribución de la especie Sceloporus undulatus bajo las recientes condiciones climáticas y bajo un escenario de calentamiento global mediante la combinación de datos microclimáticos, funciones del desarrollo y modelos biofísicos. Pronosticamos que la OD declinará conforme la temperatura aumente en 74.8% de los 11407 sitios. La disminución del éxito de eclosión y de la energía de las crías explicó más horas perdidas de OD (72.6% y 72.9%) que la presencia de estrés por calor en las crías (59.9%). Una anidación más profunda (a una profundidad de 12 cm) puede ser un ajuste conductual más efectivo para la retención de la OD que los nidos con mayor sombreado (50% de sombra) porque el primero mitigó por completo la declinación de la OD bajo el escenario de calentamiento en más sitios (66.1%) que el segundo ajuste (28.3%). Defendemos el uso de la OD en el pronóstico del impacto del calentamiento global sobre los animales ovíparos porque encapsula los impactos integrales que tiene el calentamiento global sobre todas las etapas de la vida reproductiva. 气候变化在寒冷和温暖地区对物种产卵机会造成不同影响.

Detection of Audio Tampering Based on Electric Network Frequency Signal.

The detection of audio tampering plays a crucial role in ensuring the authenticity and integrity of multimedia files. This paper presents a novel approach to identifying tampered audio files by leveraging the unique Electric Network Frequency (ENF) signal, which is inherent to the power grid and serves as a reliable indicator of authenticity. The study begins by establishing a comprehensive Chinese ENF database containing diverse ENF signals extracted from audio files. The proposed methodology involves extracting the ENF signal, applying wavelet decomposition, and utilizing the autoregressive model to train effective classification models. Subsequently, the framework is employed to detect audio tampering and assess the influence of various environmental conditions and recording devices on the ENF signal. Experimental evaluations conducted on our Chinese ENF database demonstrate the efficacy of the proposed method, achieving impressive accuracy rates ranging from 91% to 93%. The results emphasize the significance of ENF-based approaches in enhancing audio file forensics and reaffirm the necessity of adopting reliable tamper detection techniques in multimedia authentication.

miR-21 Targets Long Noncoding RNA PCAT29 to Promote Cell Proliferation in Neuroblastoma.

Long noncoding RNA (lncRNA) PCAT29 has been characterized as a tumor suppressor in several types of cancer, although its involvement in neuroblastoma (NB) is unknown. In this study, we analyzed the role of PCAT29 in NB. In paired NB and nontumor tissues from 56 patients with NB, microRNA (miR)-21 and PCAT29 expression was determined with reverse transcription quantitative PCR. Correlation between miR-21 and PCAT29 was evaluated with linear regression. The interaction between miR-21 and PCAT29 was predicted by the IntaRNA 2.0 program. In NB cells, miR-21 and PCAT29 were overexpressed to explore their relationship. In NB cell proliferation, the roles of miR-21 and PCAT29 were analyzed with propidium iodide staining and Ki67 staining assays. The results showed that PCAT29 was downregulated and miR-21 was upregulated in NB. MiR-21 was inversely correlated with PCAT29. RNA-RNA interaction prediction revealed that miR-21 might target PCAT29. MiR-21 overexpression reduced PCAT29 expression and increased NB cell proliferation, whereas PCAT29 overexpression inhibited NB cell proliferation. PCAT29 overexpression promoted NB cell apoptosis, while miR-21 overexpression inhibited NB cell apoptosis and attenuated PCAT29 overexpression-mediated NB cell apoptosis. In conclusion, MiR-21 may target PCAT29 to promote cell apoptosis in NB.