A novel SERS-lateral flow assay (LFA) tray for monitoring of miR-155-5p during pyroptosis in breast cancer cells.

In the study, a novel surface-enhanced Raman scattering (SERS)-lateral flow assay (LFA) tray for the real-time detection of pyroptosis-associated miR-155-5p in breast cancer cells was established and validated. The SERS probe modified with monoclonal antibodies and functionalized HP1@5-FAM was first synthesized. When miR-155-5p was present, HP1@5-FAM on the SERS probe specifically recognized target miRNAs and hybridized with them, resulting in HP2 on the T line only capturing some SERS probes that were not bound to miR-155-5p. The T line appeared as a light orange band or there was no color change, and the corresponding Raman detection result showed a weak or insignificant Raman signal. The SERS probe showed high selectivity, satisfactory stability, and excellent reproducibility, and the limit of detection (LOD) for miR-155-5p was 7.26 aM. Finally, the proposed SERS-LFA tray was applied to detect miR-155-5p in MBA-MD-468 cells that underwent varying degrees of pyroptosis, and the detection results of SERS were consistent with those of the conventional real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay. The study demonstrated that the SERS-LFA tray was a convenient and ultrasensitive method for miR-155-5p real-time detection, which could provide more detailed information for pyroptosis and be of potential value in guiding the treatment of breast cancer.

Honeycomb effect elimination in differential phase fiber-bundle-based endoscopy.

Fiber-bundle-based endoscopy, with its ultrathin probe and micrometer-level resolution, has become a widely adopted imaging modality for in vivo imaging. However, the fiber bundles introduce a significant honeycomb effect, primarily due to the multi-core structure and crosstalk of adjacent fiber cores, which superposes the honeycomb pattern image on the original image. To tackle this issue, we propose an iterative-free spatial pixel shifting (SPS) algorithm, designed to suppress the honeycomb effect and enhance real-time imaging performance. The process involves the creation of three additional sub-images by shifting the original image by one pixel at 0, 45, and 90 degree angles. These four sub-images are then used to compute differential maps in the x and y directions. By performing spiral integration on these differential maps, we reconstruct a honeycomb-free image with improved details. Our simulations and experimental results, conducted on a self-built fiber bundle-based endoscopy system, demonstrate the effectiveness of the SPS algorithm. SPS significantly improves the image quality of reflective objects and unlabeled transparent scattered objects, laying a solid foundation for biomedical endoscopic applications.

Transgenic expression of artificial microRNA targeting soybean mosaic virus P1 gene confers virus resistance in plant.

RNA silencing is an innate immune mechanism of plants against invasion by viral pathogens. Artificial microRNA (amiRNA) can be engineered to specifically induce RNA silencing against viruses in transgenic plants and has great potential for disease control. Here, we describe the development and application of amiRNA-based technology to induce resistance to soybean mosaic virus (SMV), a plant virus with a positive-sense single-stranded RNA genome. We have shown that the amiRNA targeting the SMV P1 coding region has the highest antiviral activity than those targeting other SMV genes in a transient amiRNA expression assay. We transformed the gene encoding the P1-targeting amiRNA and obtained stable transgenic Nicotiana benthamiana lines (amiR-P1-3-1-2-1 and amiR-P1-4-1-2-1). Our results have demonstrated the efficient suppression of SMV infection in the P1-targeting amiRNA transgenic plants in an expression level-dependent manner. In particular, the amiR-P1-3-1-2-1 transgenic plant showed high expression of amiR-P1 and low SMV accumulation after being challenged with SMV. Thus, a transgenic approach utilizing the amiRNA technology appears to be effective in generating resistance to SMV.

RENAL PROTECTIVE EFFECT AND CLINICAL ANALYSIS OF VITAMIN B 6 IN PATIENTS WITH SEPSIS.

ABSTRACT: Objective: To investigate the protective effect and possible mechanisms of vitamin B 6 against renal injury in patients with sepsis. Methods: A total of 128 patients with sepsis who met the entry criteria in multiple centers were randomly divided into experimental (intravenous vitamin B 6 therapy) and control (intravenous 0.9% sodium chloride therapy) groups based on usual care. Clinical data, the inflammatory response indicators interleukin 6 (IL-6), interleukin 8 (IL-8), tumor necrosis factor (TNF-α), and endothelin-1 (ET-1), the oxidative stress response indicators superoxide dismutase, glutathione and malondialdehyde, and renal function (assessed by blood urea nitrogen, serum creatinine, and renal resistance index monitored by ultrasound) were compared between the two groups. Results: After 7 d of treatment, the IL-6, IL-8, TNF-α, and ET-1 levels in the experimental group were significantly lower than those in the control group, the oxidative stress response indicators were significantly improved in the experimental group and the blood urea nitrogen, serum creatinine, and renal resistance index values in the experimental group were significantly lower than those in the control group ( P < 0.05). There was no statistical difference between the two groups in the rate of renal replacement therapy and 28 d mortality ( P > 0.05). However, the intensive care unit length of stay and the total hospitalization expenses in the experimental group were significantly lower than those in the control group ( P < 0.05). Conclusion: The administration of vitamin B 6 in the treatment of patients with sepsis attenuates renal injury, and the mechanism may be related to pyridoxine decreasing the levels of inflammatory mediators and their regulation by redox stress.

The Inverted U-Shaped Association between Serum Vitamin D and Serum Uric Acid Status in Children and Adolescents: A Large Cross-Sectional and Longitudinal Analysis.

BACKGROUND: Serum vitamin D is associated with hyperuricemia. However, previous studies have been controversial, with limited focus on children and adolescents. OBJECTIVE: This study aimed to examine the cross-sectional and longitudinal associations between serum vitamin D and serum uric acid (SUA) levels in children and adolescents. METHODS: The cross-sectional survey comprised 4777 participants aged 6 to 18 years, while the longitudinal survey involved 1641 participants aged 6 to 12 years, all derived from an ongoing cohort study in Shenzhen, China. Restricted cubic splines were used to visualize the dose-response relationship between vitamin D and SUA and the risk of higher SUA status. Two-segment generalized linear models (GLM) and logistic models were used to assess the association between vitamin D and SUA and higher SUA status, respectively. The longitudinal analysis used GLM. RESULTS: We observed an inverted U-shaped relationship between vitamin D and SUA (p-overall < 0.0001, p-nonlinear = 0.0002), as well as the risk of higher SUA status (p-overall = 0.0054, p-nonlinear = 0.0015), with the vitamin D inflection point at 24.31 and 21.29 ng/mL, respectively. A 10 ng/mL increment in 25(OH)D3 levels, when below 20.92 ng/mL, was associated with a 68% rise in the risk of higher SUA status (OR: 1.68, 95%CI: 1.07-2.66). Conversely, when 25(OH)D3 levels were above or equal to 20.92 ng/mL, a 10 ng/mL increment was associated with a 45% reduction risk of higher SUA status (OR: 0.55, 95%CI: 0.36-0.84). Longitudinal analysis indicated that the annual change of SUA was from -4.80 (ß, 95%CI: -10.74, 1.13) to -9.00 (ß, 95%CI: -15.03, -2.99) and then to -6.77 (ß, 95%CI: -12.83, -0.71, p for trend = 0.0212) µmol/L when increasing the quartile of vitamin D3. CONCLUSIONS: An inverse U-shaped relationship was observed between vitamin D and SUA as well as the risk of higher SUA status. Sufficient vitamin D levels appear to play a preventative role against the age-related increase in SUA. Ensuring adequate vitamin D levels may be beneficial in improving uric acid metabolism.

Abnormal Bone Turnover Observed in Obese Children Based on Puberty Stage -Specific Bone Turnover Marker Reference.

CONTEXT: Childhood and adolescence are critical periods for lifelong bone health. The impact of obesity on these phases is controversial, which may be due to the lack of standards for age-, sex-, and puberty-specific Bone turnover markers (BTMs) which could sensitively reflect bone metabolism. OBJECTIVE: To generate age-, sex, and puberty stage-specific BTMs reference curves in children and adolescents and to explore the effect of obesity on bone metabolism in the Chinese population. METHODS: Our study was part of the Evaluation and Monitoring on School-based Nutrition and Growth in Shenzhen study. 800 participants aged 6∼18 years with normal body mass index (BMI) were selected to establish BTM reference curves for boys and girls at different ages under different pubertal development stages. Additionally, 200 participants with obesity (BMI >P95th) were matched with healthy children from the original cohort at a 1:1 ratio. All participants underwent bone mineral density assessment, and serum levels of P1NP and ß-CTX were measured. RESULTS: The BTMs values presented significant age, sex, and puberty stage differences. Analysis of serum BTMs based on the established reference revealed a higher percentage of low-level P1NP in boys with obesity (P=0.005); no significant difference was observed in girls. However, the obese group showed a significantly higher proportion of high ß-CTX levels for girls, not boys (P=0.022). CONCLUSIONS: We provide age-, sex-, and puberty stage-specific P1NP and ß-CTX reference curve. According to these, obesity appeared to be a negative factor for bone formation in boys and for bone resorption in girls.

The Impact of New Regulations on Prevention and Control of E-Cigarettes on Adolescents in Middle Schools - A City in China, 2022-2023.

What is already known about this topic?: To protect the health of young people from the harmful impacts of electronic cigarettes (e-cigarettes), China has enacted various policies and regulations since 2018. As of October 1, 2022, the Electronic Cigarette Management Measures were put into action. They prohibited the sale of flavored e-cigarettes, permitting only those of plain tobacco flavor to be sold. What is added by this report?: The illegal market for flavored e-cigarettes, often disguised as milk tea cups, cola cans, and violent bear images, continues to flourish. There is an increased need to bolster support for the prohibition of flavored e-cigarettes and enhance public awareness of associated regulations. What are the implications for public health practice?: To advance the health of China's youth, it is crucial to improve the implementation and understanding of e-cigarette policies and guidelines.

Gradient-induced long-range optical pulling force based on photonic band gap.

Optical pulling provides a new degree of freedom in optical manipulation. It is generally believed that long-range optical pulling forces cannot be generated by the gradient of the incident field. Here, we theoretically propose and numerically demonstrate the realization of a long-range optical pulling force stemming from a self-induced gradient field in the manipulated object. In analogy to potential barriers in quantum tunnelling, we use a photonic band gap design in order to obtain the intensity gradients inside a manipulated object placed in a photonic crystal waveguide, thereby achieving a pulling force. Unlike the usual scattering-type optical pulling forces, the proposed gradient-field approach does not require precise elimination of the reflection from the manipulated objects. In particular, the Einstein-Laub formalism is applied to design this unconventional gradient force. The magnitude of the force can be enhanced by a factor of up to 50 at the optical resonance of the manipulated object in the waveguide, making it insensitive to absorption. The developed approach helps to break the limitation of scattering forces to obtain long-range optical pulling for manipulation and sorting of nanoparticles and other nano-objects. The developed principle of using the band gap to obtain a pulling force may also be applied to other types of waves, such as acoustic or water waves, which are important for numerous applications.

Damage Monitoring of Regularly Arrayed Short-Fiber-Reinforced Composite Laminates under Tensile Load Based on Acoustic Emission Technology.

Carbon-fiber-reinforced polymer (CFRP) composites are widely used in lightweight structures because of their high specific strength, specific modulus, and low coefficient of thermal expansion. Additionally, the unidirectionally arrayed chopped strand (UACS) laminates have excellent mechanical properties and flowability, making them suitable for fabricating structures with complex geometry. In this paper, the damage process of UACS quasi-isotropic laminates under tensile load was tested using acoustic emission detection technology. The mechanical properties and damage failure mechanism of UACS laminates were studied combined with finite element calculation. By comparing and analyzing the characteristic parameters of acoustic emission signals such as amplitude, relative energy, and impact event, it is found that acoustic emission behavior can accurately describe the damage evolution of specimens during loading. The results show that the high-amplitude signals representing fiber fracture in continuous fiber laminates are concentrated in the last 41%, while in UACS laminates they are concentrated in the last 30%. In UACS laminates, more of the damage is caused by matrix cracks and delamination with medium- and low-amplitude signals, which indicates that UACS laminates have a good suppression effect on damage propagation. The stress-strain curves obtained from finite element analysis agree well with the experiment results, showing the same damage sequence, which confirms that the model described in this research is reliable.

Association of serum 25-hydroxyvitamin D with bone health measured by calcaneal quantitative ultrasound: a large cross-sectional analysis in children and adolescents.

Background: Vitamin D plays a crucial role in bone health; however, findings in children and adolescents remain inconsistent, and few studies have examined its impact on bone health measured by quantitative ultrasound (QUS). This study aims at assessing the relationship between serum vitamin D levels and bone health, as evaluated by QUS, across varying pubertal stages and genders. Methods: A baseline cross-sectional survey of an ongoing cohort study included 4682 children and adolescents aged 6 to 18 years from Shenzhen, China. Serum levels of 25-hydroxyvitamin D (25(OH)D), which is the sum of 25(OH)D2 and 25(OH)D3, were quantified using liquid chromatography-mass spectrometry. Bone health was measured through calcaneal QUS, utilizing the speed of sound (SOS) in the heel as a principal measure-a higher SOS indicating a denser bone structure. Generalized linear models were used to evaluate the association of serum 25(OH)D, 25(OH)D2, and 25(OH)D3 levels with the SOS. Results: Forty-one point-one percent of this population was vitamin D deficient (serum 25(OH)D < 20 ng ml-1), with only 11.1% being sufficient. In the fully adjusted model, we observed a significant positive association between increased serum 25(OH)D quartiles and SOS. Compared with the participants in the lowest quartiles of serum 25(OH)D, those in successive quartiles of 25(OH)D were 3.54 (95% CI: 0.81, 6.28) m s-1, 5.74 (95% CI: 2.87, 8.61) m s-1, and 8.83 (95% CI: 5.83, 11.84) m s-1, respectively (P for trend < 0.0001). The correlations observed for serum 25(OH)D2 and 25(OH)D3 with SOS were similar to those of serum 25(OH)D. Importantly, this association was primarily observed in post-pubertal children and adolescents but was absent in pre- and mid-pubertal participants (P for interaction = 0.0004). Conclusion: Elevated serum 25(OH)D levels were associated with better bone health, as measured through calcaneal QUS, in children and adolescents, particularly among those who had reached the post-pubertal stage. These findings highlight the crucial importance of maintaining sufficient vitamin D levels to support optimal bone health in this demographic.

Worldwide trends in mortality for hypertensive heart disease from 1990 to 2019 with projection to 2034: data from the Global Burden of Disease 2019 study.

AIMS: This study aims to analyse the worldwide trends in hypertensive heart disease (HHD) mortality and associations with age, period, and birth cohort and predict the future burden of HHD deaths. METHODS AND RESULTS: Mortality estimates were obtained from Global Burden of Disease 2019 study. We used age-period-cohort (APC) model to examine the age, period, and cohort effects on HHD mortality between 1990 and 2019. Bayesian APC model was utilized to predict HHD deaths to 2034. The global HHD deaths were 1.16 million in 2019 and were projected to increase to 1.57 million in 2034, with the largest increment in low- and middle-income countries (LMICs). Between 1990 and 2019, middle/high-middle socio-demographic index (SDI) countries had the largest mortality reductions (annual percentage change = -2.06%), whereas low SDI countries saw a lagging performance (annual percentage change = -1.09%). There was a prominent transition in the age distribution of deaths towards old-age population in middle/high-middle SDI countries, while the proportion of premature deaths (aged under 60 years) remained at 24% in low SDI countries in 2019. Amongst LMICs, Brazil, China, and Ethiopia showed typically improving trends both over time and in recent birth cohorts, whereas 63 countries including Indonesia, the Philippines, and Pakistan had unfavourable or worsening risks for recent periods and birth cohorts. CONCLUSION: The HHD death burden in 2019 is vast and is expected to increase rapidly in the next decade, particularly for LMICs. Limited progress in HHD management together with high premature mortality would exact huge human and medical costs in low SDI countries. The examples from Brazil, China, and Ethiopia suggest that efficient health systems with action on improving hypertension care can reduce HHD mortality effectively in LMICs.

This study provides the first comprehensive analysis of the age, period, and cohort trends in mortality for hypertensive heart disease (HHD) across 204 countries and territories from 1990 to 2019, with projection to 2034. The death burden of HHD is substantial and growing rapidly in most of the world, particularly in low- and middle-income countries (LMICs). Wide disparities exist within LMICs in HHD management, with most low socio-demographic index countries showing little progress in reducing HHD mortality. The examples from Brazil, China, and Ethiopia suggest that prevention policies for HHD can reduce risks for younger birth cohorts and shift the risks for all age groups over time.

Quantitative evaluation on thermal seeing induced 2m ring solar telescope.

Thermal seeing is one of the factors that affect solar telescope observations. A comprehensive analysis method is developed to quantify the thermal seeing effects. A three-dimensional Large Eddy Simulation (LES) turbulence model is used to obtain the transient flow fields around the primary mirror, the secondary mirror and the heat-stop. The thermal seeing is calculated based on the stochastic dynamic influence of turbulence on the light rays. The key parameters of the simulation were calibrated by experiments, and the simulation results were validated by empirical formulas. This method has been applied to evaluate the thermal seeing of the 2m Ring Solar Telescope (2m-RST). Error allocation is performed based on the research results to ensure the Observation effect of 2m-RST.

LORF9 of Marek's disease virus is involved in the early cytolytic replication of B lymphocytes and can act as a target for gene deletion vaccine development.

IMPORTANCE: Marek's disease virus (MDV) is a highly infectious and oncogenic virus that can induce severe T cell lymphomas in chickens. MDV encodes more than 100 genes, most of which have unknown functions. This work indicated that the LORF9 gene is necessary for MDV early cytolytic replication in B lymphocytes. In addition, we have found that the LORF9 deletion mutant has a comparative immunological protective effect with CVI988/Rispens vaccine strain against very virulent MDV challenge. This is a significant discovery that LORF9 can be exploited as a possible target for the development of an MDV gene deletion vaccine.

Establishment and characterization of a novel indirect ELISA method based on ASFV antigenic epitope-associated recombinant protein.

African Swine Fever (ASF) is an acute and highly lethal disease in pigs caused by African Swine Fever Virus (ASFV). Viral proteins have been commonly used as antigenic targets for the development of ASF diagnostic methods. However, the prokaryotic expression of viral proteins has deficiencies such as instability, insolubility, and high cost in eukaryotic situations. This study screened and verified ASFV-encoded p72, p54, and p30 protein antigenic epitopes. Subsequently, a novel antigenic epitope-associated recombinant protein was designed based on an ideal structural protein and expressed in Escherichia coli (E. coli). Western blot analysis indicated that the recombinant protein could specifically react with the monoclonal antibody (mAb) of p72 and polyclonal antibodies of p54 and p30, respectively. Next, an ASF indirect ELISA (iELISA) method was established based on the recombinant protein, which has no specific reaction with sera of other important pig viral diseases. Meanwhile, it shows a sensitivity to detecting dilutions of ASF-positive reference serum up to 1:6400. The clinical sample detection results showed a high coincidence rate of 98 % with a commercial competition ELISA kit. In conclusion, we established a novel specific, and sensitive ASF serologic detection method that opens new avenues for ASF serodiagnostic method development.

An Intracellular Epitope of ASFV CD2v Protein Elicits Humoral and Cellular Immune Responses.

The African swine fever virus (ASFV) causes high mortality in domestic pigs. ASFV encodes an important protein target for subunit vaccine development, CD2v, but its most effective immunological regions are not known. Herein, we generated a monoclonal antibody (mAb) named IF3 by immunizing mice against the intracellular region of the CD2v protein (CD2v-IR). 1F3 specifically recognized CD2v, which is expressed transiently in transfected Sf9 cells and also in inactivated ASFV-infected porcine alveolar macrophage (PAM) cells. The epitope recognized by 1F3 is 264EPSPREP270, which is highly conserved in ASFV genotypes. Immunization of mice with this epitope elicited an increased IgG response, including IgG1 and IgG2a subtypes, and also increased CD8+ T cells and cytokine expression. Overall, these results indicate that this epitope induces both humoral and cellular immune responses that may be used for ASFV-related subunit vaccine design and development.

CIRP attenuates acute kidney injury after hypothermic cardiovascular surgery by inhibiting PHD3/HIF-1α-mediated ROS-TGF-ß1/p38 MAPK activation and mitochondrial apoptotic pathways.

BACKGROUND: The ischemia-reperfusion (IR) environment during deep hypothermic circulatory arrest (DHCA) cardiovascular surgery is a major cause of acute kidney injury (AKI), which lacks preventive measure and treatment. It was reported that cold inducible RNA-binding protein (CIRP) can be induced under hypoxic and hypothermic stress and may have a protective effect on multiple organs. The purpose of this study was to investigate whether CIRP could exert renoprotective effect during hypothermic IR and the potential mechanisms. METHODS: Utilizing RNA-sequencing, we compared the differences in gene expression between Cirp knockout rats and wild-type rats after DHCA and screened the possible mechanisms. Then, we established the hypothermic oxygen-glucose deprivation (OGD) model using HK-2 cells transfected with siRNA to verify the downstream pathways and explore potential pharmacological approach. The effects of CIRP and enarodustat (JTZ-951) on renal IR injury (IRI) were investigated in vivo and in vitro using multiple levels of pathological and molecular biological experiments. RESULTS: We discovered that Cirp knockout significantly upregulated rat Phd3 expression, which is the key regulator of HIF-1α, thereby inhibiting HIF-1α after DHCA. In addition, deletion of Cirp in rat model promoted apoptosis and aggravated renal injury by reactive oxygen species (ROS) accumulation and significant activation of the TGF-ß1/p38 MAPK inflammatory pathway. Then, based on the HK-2 cell model of hypothermic OGD, we found that CIRP silencing significantly stimulated the expression of the TGF-ß1/p38 MAPK inflammatory pathway by activating the PHD3/HIF-1α axis, and induced more severe apoptosis through the mitochondrial cytochrome c-Apaf-1-caspase 9 and FADD-caspase 8 death receptor pathways compared with untransfected cells. However, silencing PHD3 remarkably activated the expression of HIF-1α and alleviated the apoptosis of HK-2 cells in hypothermic OGD. On this basis, by pretreating HK-2 and rats with enarodustat, a novel HIF-1α stabilizer, we found that enarodustat significantly mitigated renal cellular apoptosis under hypothermic IR and reversed the aggravated IRI induced by CIRP defect, both in vitro and in vivo. CONCLUSION: Our findings indicated that CIRP may confer renoprotection against hypothermic IRI by suppressing PHD3/HIF-1α-mediated apoptosis. PHD3 inhibitors and HIF-1α stabilizers may have clinical value in renal IRI.

Prevalence and associated factors of smoking among chinese adolescents: a school-based cross-sectional study.

BACKGROUND: Shenzhen has made great efforts to address the tobacco epidemic in the past decade. This study aims to evaluate the current status of the tobacco epidemic among adolescent in Shenzhen, China. METHODS: The multi-stage random cluster sampling method was used in the school-based cross-sectional study in 2019 and a total of 7,423 junior and high school (both senior and vocational) students were recruited. Information on cigarette use was collected by the electronic questionnaire. Logistic regression analysis was used to examine the associations between current cigarette use and associated factors. ORs with their 95% CIs were reported. RESULTS: The prevalence of current cigarette use among adolescents was 2.3%, with boys (3.4%) significantly higher than girls (1.0%). Smoking rates in junior high schools, senior high schools, and vocational senior high schools were 1.0%, 2.7%, and 4.1%, respectively. The results of multivariate logistic regression analysis indicated that gender, age, parental smoking, teachers smoking in schools, friends smoking, exposure to tobacco marketing, and misconceptions about cigarette use were associated factors for adolescent smoking behaviour. CONCLUSIONS: The prevalence of current smoking was relatively low among adolescent in Shenzhen, China. Personal characteristics, family, and school were associated with current adolescent smokers.

Hybrids of delavirdine and piperdin-4-yl-aminopyrimidines (DPAPYs) as potent HIV-1 NNRTIs: Design, synthesis and biological activities.

The hybrids of delavirdine and piperdin-4-yl-aminopyrimidine (DPAPYs) were designed from two excellent HIV-1 NNRTIs delavirdine and piperidin-4-yl-aminopyrimidine via molecular hybridization. The target compounds 4a-r were prepared and evaluated for their cellular anti-HIV activities and cytotoxicities as well as the inhibitory activities against HIV-1 reverse transcriptase (RT). All the newly synthesized compounds demonstrated moderate to excellent potency against wild-type (WT) HIV-1 with EC50 values in a range of 5.7 to 0.0086 µM and against RT with IC50 values ranging from 12.0 to 0.11 µM, indicating that the DPAPYs were specific RT inhibitors. Among all, 4d displayed the most potent activity against WT HIV-1 (EC50 = 8.6 nM, SI = 2151). Gratifyingly, it exhibited good to excellent potency against the single HIV-1 mutants L100I, K103N, Y181C, Y188L, E138K, as well as the double mutant F227L + V106A. Furthermore, the preliminary structure-activity relationships were summarized, molecular modeling was conducted to explore the binding mode of DPAPYs and HIV-1 RT, and their physicochemical properties were also predicted.

Infection phase-dependent dynamics of the viral and host N6-methyladenosine epitranscriptome in the lifecycle of an oncogenic virus in vivo.

Dynamic alteration of the epitranscriptome exerts regulatory effects on the lifecycle of oncogenic viruses in vitro. However, little is known about these effects in vivo because of the general lack of suitable animal infection models of these viruses. Using a model of rapid-onset Marek's disease lymphoma in chickens, we investigated changes in viral and host messenger RNA (mRNA) N6-methyladenosine (m6 A) modification during Marek's disease virus (MDV) infection in vivo. We found that the expression of major epitranscriptomic proteins varies among viral infection phases, reprogramming both the viral and the host epitranscriptomes. Specifically, the methyltransferase-like 3 (METTL3)/14 complex was suppressed during the lytic and reactivation phases of the MDV lifecycle, whereas its expression was increased during the latent phase and in MDV-induced tumors. METTL3/14 overexpression inhibits, whereas METTL3/14 knockdown enhances, MDV gene expression and replication. These findings reveal the dynamic features of the mRNA m6 A modification program during viral replication in vivo, especially in relation to key pathways involved in tumorigenesis.