Identification and validation of UBE2B as a prognostic biomarker promoting the development of esophageal carcinomas.

Introduction: Ubiquitination is a crucial biological mechanism in humans, essential for regulating vital biological processes, and has been recognized as a promising focus for cancer therapy. Our objective in this research was to discover potential enzymes associated with ubiquitination that may serve as therapeutic targets for individuals with esophageal carcinoma (ESCA). Methods: To identify genes linked to the prognosis of ESCA, we examined mRNA sequencing data from patients with ESCA in the TCGA database. Further investigation into the role of the candidate gene in ESCA was conducted through bioinformatic analyses. Subsequently, we carried out biological assays to assess its impact on ESCA development. Results: Through univariate Cox regression analysis, we identified Ubiquitin Conjugating Enzyme E2 B (UBE2B) as a potential gene associated with the prognosis of ESCA. UBE2B exhibited significant upregulation and was found to be correlated with survival outcomes in ESCA as well as other cancer types. Additionally, UBE2B was observed to be involved in various biological pathways linked to the development of ESCA, including TNF-a signaling via NF-κB, epithelial-mesenchymal transition, inflammatory response, and hypoxia. Moreover, immune-related pathways like B cell activation (GO: 0042113), B cell receptor signaling pathway (GO: 0050853) and B cell mediated immunity (GO:0019724) were also involved. It was found that high expression of UBE2B was correlated with the increase of several kinds of T cells (CD8 T cells, Th1 cells) and macrophages, while effector memory T cell (Tem) and Th17 cells decreased. Furthermore, UBE2B showed potential as a prognostic biomarker for ESCA, displaying high sensitivity and specificity. Notably, proliferation and migration in ESCA cells were effectively suppressed when the expression of UBE2B was knocked down. Conclusions: To summarize, this study has made a discovery regarding the importance of gaining new insights into the role of UBE2B in ESCA. UBE2B might be an oncogene with good ability in predicting and diagnosing ESCA. Consequently, this discovery highlights the feasibility of targeting UBE2B as a viable approach for treating patients with ESCA.

Study of thermal effects induced by the high-frequency probing laser in nonlinear opto-acoustic frequency-mixing technique.

Photo-thermal modulation-based nonlinear opto-acoustic frequency-mixing technique is an effective method for detecting micro-cracks. When using this technique for micro-crack detection, the selection of laser source parameters is particularly crucial. Compared to traditional piezo-transducer-based mixing techniques, the characteristic of using a laser as the detection source is the presence of thermal effects. The thermal effect caused by laser irradiation on the sample surface can not only generate acoustic waves but also affect the crack state, thus influencing nonlinear signals. In this paper, an experimental setup using photo-thermal modulation-based nonlinear opto-acoustic frequency-mixing technique has been set up to investigate the thermal effects of the probe laser source. In addition, a corresponding physical model has been established to discuss the physical mechanisms revealed by the experimental results. This study provides a basis for selecting appropriate probe source parameters and scanning positions of laser sources when detecting micro-cracks using the photo-thermal modulation-based nonlinear opto-acoustic frequency-mixing technique.

Biocontrol and Growth Promotion Potential of Bacillus subtilis CTXW 7-6-2 against Rhizoctonia solani that Causes Tobacco Target Spot Disease.

Fungal diseases form perforated disease spots in tobacco plants, resulting in a decline in tobacco yield and quality. The present study investigated the antagonistic effect of Bacillus subtilis CTXW 7-6-2 against Rhizoctonia solani, its ability to promote the growth of tobacco seedlings, and the expression of disease resistance-related genes for efficient and eco-friendly plant disease control. Our results showed that CTXW 7-6-2 had the most vigorous growth after being cultured for 96 h, and its rate of inhibition of R. solani growth in vitro was 94.02%. The volatile compounds produced by CTXW 7-6-2 inhibited the growth of R. solani significantly (by 96.62%). The fungal growthinhibition rate of the B. subtilis CTXW 7-6-2 broth obtained after high-temperature and no-high-temperature sterile fermentation was low, at 50.88% and 54.63%, respectively. The lipopeptides extracted from the B. subtilis CTXW 7-6-2 fermentation broth showed a 74.88% fungal growth inhibition rate at a concentration of 100 mg/l. Scanning and transmission electron microscopy showed some organelle structural abnormalities, collapse, shrinkage, blurring, and dissolution in the R. solani mycelia. In addition, CTXW 7-6-2 increased tobacco seedling growth and improved leaf and root weight compared to the control. After CTXW 7-6-2 inoculation, tobacco leaves showed the upregulation of the PDF1.2, PPO, and PAL genes, which are closely related to target spot disease resistance. In conclusion, B. subtilis CTXW 7-6-2 may be an efficient biological control agent in tobacco agriculture and enhance plant growth potential.

Short-term exposure to gaseous pollutants is neglected factors for knee osteoarthritis: evidence from a humid subtropical region of China.

Few studies were performed on the impact of exposure to gaseous pollutants on the risk of knee osteoarthritis (KOA). We conducted this study to analyze the association between short-term exposure to gaseous pollutants and the risk of hospitalizations for KOA. A total of 2952 KOA hospitalizations derived from two hospitals in Hefei, and the relationship between gaseous pollutants and KOA hospitalizations was analyzed by a distributed lag non-linear model combined with a generalized linear model. We found that the decreased risk of hospitalizations for KOA were both related to exposure to NO2 (RR = 0.993, lag19 day) and O3 (RR = 0.984, lag0 day), while exposure to CO could increase the risk of hospitalizations for KOA (RR = 1.076, lag2 day). Stratified analyses suggested that the KOA patients < 65 years were more susceptible to O3 exposure, and the female, male, patients ≥ 65 years, and patients < 65 years were both more sensitive to CO exposure. Our findings demonstrated that exposure to NO2, O3 resulted in a decreased risk for KOA hospitalizations, and CO exposure might increase the risk of KOA hospitalizations.

Effect of Reactive Oxygen Scavenger N,N'-Dimethylthiourea (DMTU) on Seed Germination and Radicle Elongation of Maize.

Reactive oxygen species (ROS) are an important part of adaptation to biotic and abiotic stresses and regulate seed germination through positive or negative signaling. Seed adaptation to abiotic stress may be mediated by hydrogen peroxide (H2O2). The effects of the ROS scavenger N,N'-dimethylthiourea (DMTU) on maize seed germination through endogenous H2O2 regulation is unclear. In this study, we investigated the effects of different doses of DMTU on seed endogenous H2O2 and radicle development parameters using two maize varieties (ZD958 and DMY1). The inhibitory effect of DMTU on the germination rate and radicle growth was dose-dependent. The inhibitory effect of DMTU on radicle growth ceased after transferring maize seeds from DMTU to a water medium. Histochemical analyses showed that DMTU eliminated stable H2O2 accumulation in the radicle sheaths and radicles. The activity of antioxidant enzyme and the expression of antioxidant enzyme-related genes (ZmAPX2 and ZmCAT2) were reduced in maize seeds cultured with DMTU compared with normal culture conditions (0 mmol·dm-3 DMTU). We suggest the use of 200 mmol·dm-3 DMTU as an H2O2 scavenger to study the ROS equilibrium mechanisms during the germination of maize seeds, assisting in the future with the efficient development of plant growth regulators to enhance the seed germination performance of test maize varieties under abiotic stress.

Integrative analysis of DNA methylome and transcriptome reveals epigenetic regulation of bisphenols-induced cardiomyocyte hypertrophy.

Cardiac hypertrophy, a kind of cardiomyopathic abnormality, might trigger heart contractile and diastolic dysfunction, and even heart failure. Currently, bisphenols (BPs) including bisphenol A (BPA), and its alternatives bisphenol AF (BPAF), bisphenol F (BPF) and bisphenol S (BPS) are ubiquitously applied in various products and potentially possess high cardiovascular risks for humans. However, the substantial experimental evidences of BPs on heart function, and their structure-related effects on cardiomyocyte hypertrophy are still urgently needed. DNA methylation, a typical epigenetics, play key roles in BPs-induced transcription dysregulation, thereby affecting human health including cardiovascular system. Thus, in this study, we performed RNA-seq and reduced representation bisulfite sequencing (RRBS) to profile the landscapes of BPs-induced cardiotoxicity and to determine the key roles of DNA methylation in the transcription. Further, the capabilities of three BPA analogues, together with BPA, in impacting heart function and changing DNA methylation and transcription were compared. We concluded that similar to BPA, BPAF, BPF and BPS exposure deteriorated heart function in a mouse model, and induced cardiomyocyte hypertrophy in a H9c2 cell line. BPAF, BPF and BPS all played BPA-like roles in both transcriptive and methylated hierarchies. Moreover, we validated the expression levels of four cardiomyocyte hypertrophy related candidate genes, Psmc1, Piptnm2, Maz and Dusp18, which were all upregulated and with DNA hypomethylation. The findings on the induction of BPA analogues on cardiomyocyte hypertrophy and DNA methylation revealed their potential detrimental risks in heart function of humans.

Peroxisome proliferator-activated receptor α agonist induces mouse hepatomegaly through the spatial hepatocyte enlargement and proliferation.

Peroxisome proliferator-activated receptor alpha (PPARα) activation-induced hepatomegaly is accompanied by hepatocyte hypertrophy around the central vein (CV) area and hepatocyte proliferation around the portal vein (PV) area. However, the molecular mechanisms underlying this spatial change of hepatocytes remains unclear. In this study, we examined the characteristics and possible reasons for the zonation distinction of hypertrophy and proliferation during PPARα activation-induced mouse liver enlargement. Mice were injected with corn oil or a typical mouse PPARα agonist WY-14643 (100 mg·kg-1·d-1, i.p.) for 1, 2, 3, 5 or 10 days. At each time point, the mice were sacrificed after the final dose, and liver tissues and serum were harvested for analysis. We showed that PPARα activation induced zonal changes in hepatocyte hypertrophy and proliferation in the mice. In order to determine the zonal expression of proteins related to hepatocyte hypertrophy and proliferation in PPARα-induced liver enlargement, we performed digitonin liver perfusion to separately destroy the hepatocytes around the CV or PV areas, and found that PPARα activation-induced increase magnitude of its downstream targets such as cytochrome P450 (CYP) 4 A and acyl-coenzyme A oxidase 1 (ACOX1) levels around the CV area were higher compared with those around the PV area. Upregulation of proliferation-related proteins such as cell nuclear antigen (PCNA) and cyclin A1 (CCNA1) after WY-14643-induced PPARα activation mainly occurred around the PV area. This study reveals that the zonal expression of PPARα targets and proliferation-related proteins is responsible for the spatial change of hepatocyte hypertrophy and proliferation after PPARα activation. These findings provide a new insight into the understanding of PPARα activation-induced liver enlargement and regeneration.

A review of cardiovascular effects and underlying mechanisms of legacy and emerging per- and polyfluoroalkyl substances (PFAS).

Cardiovascular disease (CVD) poses the leading threats to human health and life, and their occurrence and severity are associated with exposure to environmental pollutants. Per- and polyfluoroalkyl substances (PFAS), a group of widely used industrial chemicals, are characterized by persistence, long-distance migration, bioaccumulation, and toxicity. Some PFAS, particularly perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA) and perfluorohexanesulfonic acid (PFHxS), have been banned, leaving only legacy exposure to the environment and human body, while a number of novel PFAS alternatives have emerged and raised concerns, such as polyfluoroalkyl ether sulfonic and carboxylic acid (PFESA and PFECA) and sodium p-perfluorous nonenoxybenzene sulfonate (OBS). Overall, this review systematically elucidated the adverse cardiovascular (CV) effects of legacy and emerging PFAS, emphasized the dose/concentration-dependent, time-dependent, carbon chain length-dependent, sex-specific, and coexposure effects, and discussed the underlying mechanisms and possible prevention and treatment. Extensive epidemiological and laboratory evidence suggests that accumulated serum levels of legacy PFAS possibly contribute to an increased risk of CVD and its subclinical course, such as cardiac toxicity, vascular disorder, hypertension, and dyslipidemia. The underlying biological mechanisms may include oxidative stress, signaling pathway disturbance, lipid metabolism disturbance, and so on. Various emerging alternatives to PFAS also play increasingly prominent toxic roles in CV outcomes that are milder, similar to, or more severe than legacy PFAS. Future research is recommended to conduct more in-depth CV toxicity assessments of legacy and emerging PFAS and explore more effective surveillance, prevention, and treatment strategies, accordingly.

The repeatability and consistency of different methods for measuring the volume parameters of the primary rectal cancer on diffusion weighted images.

Background: To determine the reproducibility of measuring the gross total volume (GTV) of primary rectal tumor with manual and semi-automatic delineation on the diffusion-weighted image (DWI), examine the consistency of using the same delineation method on DWI images with different high b-values, and find the optimal delineation method to measure the GTV of rectal cancer. Methods: 41 patients who completed rectal MR examinations in our hospital from January 2020 to June 2020 were prospectively enrolled in this study. The post-operative pathology confirmed the lesions were rectal adenocarcinoma. The patients included 28 males and 13 females, with an average age of (63.3 ± 10.6) years old. Two radiologists used LIFEx software to manually delineate the lesion layer by layer on the DWI images (b=1000 s/mm2 and 1500 s/mm2) and used 10% to 90% of the highest signal intensity as thresholds to semi-automatically delineate the lesion and measure the GTV. After one month, Radiologist 1 performed the same delineation work again to obtain the corresponding GTV. Results: The inter- and intra-observer interclass correlation coefficients (ICC) of measuring GTV using semi-automatic delineation with 30% to 90% as thresholds were all >0.900. There was a positive correlation between manual delineation and semi-automatic delineation with 10% to 50% thresholds (P < 0.05). However, the manual delineation was not correlated with the semi-automatic delineation with 60%, 70%, 80%, and 90% thresholds. On the DWI images with b=1000 s/mm2 and 1500 s/mm2, the 95% limit of agreement (LOA%) of measuring GTV using semi-automatic delineation with 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, and 90% thresholds were -41.2~67.4, -17.8~51.5, -16.1~49.3, -26.2~50.1, -42.3~57.6, -57.1~65.4, -67.3~66.5, -101.6~91.1, -129.4~136.0, and -15.3~33.0, respectively. The time required for GTV measurement by semi-automatic delineation was significantly shorter than that of manual delineation (12.9 ± 3.6s vs 40.2 ± 13.1s). Conclusions: The semi-automatic delineation of rectal cancer GTV with 30% threshold had high repeatability and consistency, and it was positively correlated with the GTV measured by manual delineation. Therefore, the semi-automatic delineation with 30% threshold could be a simple and feasible method for measuring rectal cancer GTV.

Transition from electromagnetically-induced transparency to absorption in a single microresonator.

Electromagnetically induced transparency (EIT) and absorption (EIA) are two phenomena that can be observed in whispering-gallery-mode (WGM) optical microresonators. Transition from EIT to EIA has potential applications in optical switching, filtering and sensing. In this paper an observation of the transition from EIT to EIA in a single WGM microresonator is presented. A fiber taper is used to couple light into and out of a sausage-like microresonator (SLM) that contains two coupled optical modes with significantly different quality factors. By stretching the SLM axially the resonance frequencies of the two coupled modes are tuned to the same, a transition from EIT to EIA is then observed in the transmission spectra when the fiber taper is moved closer to the SLM. It is the special spatial distribution of the optical modes of the SLM that provide a theoretical basis for the observation.

Single-cell transcriptomic analysis deciphers key transitional signatures associated with oncogenic evolution in human intramucosal oesophageal squamous cell carcinoma.

BACKGROUND AND AIMS: The early diagnosis and intervention of oesophageal squamous cell carcinoma (ESCC) are particularly important because of the lack of effective therapies and poor prognosis. Comprehensive research on early ESCC at the single-cell level is rare due to the need for fresh and high-quality specimens obtained from ESD. This study aims to systematically describe the cellular atlas of human intramucosal ESCC. METHODS: Five paired samples of intramucosal ESCC, para-ESCC oesophageal tissues from endoscopically resected specimens and peripheral blood mononuclear cells were adopted for scRNA-seq analysis. Computational pipeline scMetabolism was applied to quantify the metabolic diversity of single cells. RESULTS: A total of 164 715 cells were profiled. Epithelial cells exhibited high intra-tumoural heterogeneity and two evolutionary trajectories during ESCC tumorigenesis initiated from proliferative cells, and then through an intermediate state, to two different terminal states of normally differentiated epithelial cells or malignant cells, respectively. The abundance of CD8+ TEX s, Tregs and PD1+ CD4+ T cells suggested an exhausted and suppressive immune microenvironment. Several genes in immune cells, such as CXCL13, CXCR5 and PADI4, were identified as new biomarkers for poor prognosis. A new subcluster of malignant cells associated with metastasis and angiogenesis that appeared at an early stage compared with progressive ESCC was also identified in this study. Intercellular interaction analysis based on ligand-receptor pairs revealed the subcluster of malignant cells interacting with CAFs via the MDK-NCL pathway, which was verified by cell proliferation assay and IHC. This indicates that the interaction may be an important hallmark in the early change of tumour microenvironment and serves as a sign of CAF activation to stimulate downstream pathways for facilitating tumour invasion. CONCLUSION: This study demonstrates the changes of cell subsets and transcriptional levels in human intramucosal ESCC, which may provide unique insights into the development of novel biomarkers and potential intervention strategies.

Design and Fabrication of a MEMS Bandpass Filter with Different Center Frequency of 8.5-12 GHz.

The design simulation and fabrication results of a bandpass filter based on micro-electro-mechanical system (MEMS) switches are presented in this paper. The MEMS filter element consists of a MEMS capacitance switch and two resonant rings that are fixed onto coplanar waveguide lines through anchor points. The micromachine characteristics of the filter could be optimized to change the center frequency from 8.5 to 12 GHz by improving the geometrical parameters; other electrical parameters of the filter, such as stopband rejection, insertion loss, and return loss at each center frequency, were simulated and calculated. In order to evaluate the MEMS filter design methodology, a filter working at 10.5 GHz fabricated with an aluminum top electrode was used, and it displayed a low insertion loss of 1.12 dB and a high stopband rejection of 28.3 dB. Compared with the simulation results, these proposed filter showed better electrical performance. Our results demonstrated that the filter with the integrated RF MEMS switch not only provides the benefit of reduced size compared with a traditional filter, but also improves stopband rejection, insertion loss, and return loss.

Bilateral symmetrical distal clavicle fractures (Neer type II): A case of rare injury.

BACKGROUND: Neer type II/bilateral distal clavicular fracture is an extremely rare injury combination, with few cases having been reported. CASE PRESENTATION: This paper reports a case of polytrauma in a 16-year-old female following a road traffic accident. The radiographs revealed distal fractures of the bilateral clavicles (Neer type II), and an open reduction and internal fixation procedure was performed. Initially, the distal fracture of the right clavicle was fixed with a six-hole hook plate before the fracture of the left clavicle was fixed using a pre-contoured lateral locking plate following reduction. At the two-year follow-up, the patient had an excellent constant score in terms of the bilateral shoulder joints. CONCLUSION: It is important to achieve stability and to aim for excellence in terms of full shoulder function in this rare combination injury.

Targeted Next-Generation Sequencing for the Diagnosis of Gene Variants in Patients with 46,XY Disorder of Sex Development.

INTRODUCTION: Disorders of sex development (DSDs) are congenital abnormalities in which chromosomal, gonadal, and anatomical sex development are atypical. One of these disorders, 46,XY DSD, is particularly difficult to diagnose and manage because its etiology and clinical phenotypes are highly heterogeneous. METHODS: We used a gene panel containing 141 genes implicated in DSDs to perform targeted next-generation sequencing (NGS) in 50 patients with 46,XY DSD. RESULTS: Gene variants were detected in 23 patients (46%). Among them, 13 patients had previously reported pathogenic or likely pathogenic variants, 9 patients had novel variants, and 1 patient had a previously reported variant of uncertain significance. Three of the novel variants were pathogenic, and the remaining were variants of uncertain significance; therefore, 16 patients had pathogenic or likely pathogenic variants according to ACMG guidelines, and the overall diagnostic rate of 46,XY DSD was 32%. The most common gene variants were SRD5A2 variants, followed by the AR variant. In addition, we analyzed the association between gene variants and clinical phenotypes. Most patients presented with multiple DSD phenotypes (i.e., two or more DSD phenotypes were observed, such as micropenis, hypospadias, and cryptorchidism), but the phenotype with the highest diagnostic rate was micropenis. CONCLUSION: Our results indicate that targeted NGS can effectively detect pathogenic gene variants in patients with 46,XY DSD.

[Clinical features of severe acute respiratory syndrome coronavirus 2 Omicron variant infection in children: an analysis of 201 cases]. / 201ä¾‹å„¿ç«¥æ–°åž‹å† çŠ¶ç— æ¯’Omicronå˜å¼‚æ ªæ„ŸæŸ“çš„ä¸´åºŠç‰¹å¾åˆ†æž.

OBJECTIVES: To study the clinical features of children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant infection. METHODS: A retrospective analysis was performed on the medical data of 201 children with coronavirus disease 2019 (COVID-19) who were hospitalized and diagnosed with SARS-CoV-2 Omicron variant infection in Quanzhou First Hospital from March 14 to April 7, 2022. Among the 201 children, there were 34 children with asymptomatic infection and 167 with symptomatic infection. The two groups were compared in terms of clinical features, results of experimental examinations, and outcome. RESULTS: Of all the 201 children, 161 (80.1%) had a history of exposure to COVID-19 patients and 132 (65.7%) had a history of COVID-19 vaccination. Among the 167 children with symptomatic infections, 151 had mild COVID-19 and 16 had common COVID-19, with no severe infection or death. Among the 101 children who underwent chest CT examination, 16 had ground glass changes and 20 had nodular or linear opacities. The mean time to nucleic acid clearance was (14±4) days for the 201 children with Omicron variant infection, and the symptomatic infection group had a significantly longer time than the asymptomatic infection group [(15±4) days vs (11±4) days, P<0.05]. The group vaccinated with one or two doses of COVID-19 vaccine had a significantly higher positive rate of IgG than the group without vaccination (P<0.05). The proportions of children with increased blood lymphocyte count in the symptomatic infection group was significantly lower than that in the asymptomatic infection group (P<0.05). Compared with the asymptomatic infection group, the symptomatic infection group had significantly higher proportions of children with increased interleukin-6, increased fibrinogen, and increased D-dimer (P<0.05). CONCLUSIONS: Most of the children with Omicron variant infection have clinical symptoms, which are generally mild. The children with symptomatic infection are often accompanied by decreased or normal blood lymphocyte count and increased levels of interleukin-6, fibrinogen, and D-dimer, with a relatively long time to nucleic acid clearance. Some of them had ground glass changes on chest CT.

Long-term treatment with the mPXR agonist PCN promotes hepatomegaly and lipid accumulation without hepatocyte proliferation in mice.

Pregnane X receptor (PXR) is highly expressed in the liver and plays a pivotal role in xenobiotic and endobiotic metabolism. We previously reported that PXR activation by its specific mouse agonist pregnenolone 16α-carbonitrile (PCN) significantly induces liver enlargement and lipid accumulation. However, the effect of long-term PCN treatment on PXR and mouse liver is still unknown. This study aimed to explore the influence of long-term administration of PCN on mouse liver and hepatic lipid homeostasis. Male C57BL/6 mice were injected intraperitoneally with PCN (100 mg/kg once a week) for 42 weeks. Serum and liver samples were collected for biochemical and histological analysis. PXR activation was investigated by Western blot. Ultra-high-performance liquid chromatography coupled with electrospray ionization high-resolution mass spectrometry (UHPLC-ESI-HRMS)-based lipidomics analysis was performed to explore the change in different lipid categories. The results showed that long-term treatment with PCN significantly promoted hepatomegaly without hepatocyte proliferation and enlargement. Long-term treatment with PCN did not upregulate PXR target proteins in mice, and there was no significant upregulation of CYP3A11, CYP2B10, UGT1A1, MRP2, or MRP4. Lipidomics analysis showed obvious hepatic lipid accumulation in the PCN-treated mice, and the most significant change was found in triglycerides (TGs). Additionally, long-term treatment with PCN had no risk for carcinogenesis. These findings demonstrated that long-term PCN treatment induces hepatomegaly and lipid accumulation without hepatocyte proliferation or enlargement.

Characterization and phylogenetic analysis of a neurovirulent Zika virus isolated from Cambodia in 2019.

The geographic range of Zika virus (ZIKV) has expanded from Asia to the Americas, leading to the 2015-2016 pandemic with enhanced neurovirulence. At present, ZIKV is continuously circulating in many Southeast Asian countries. Unfortunately, the persistent evolution of ZIKV in Southeast Asia and its influence on the biological characteristics of the virus remain incompletely understood. In this study, the in vitro and in vivo properties of a new ZIKV isolate obtained from Cambodia in 2019 (CAM/2019) were characterized and compared with those of the Cambodian strain (CAM/2010). Compared with CAM/2010, the CAM/2019 virus showed similar plaque morphology and growth curves in cell cultures and induced comparable viremia and organ viral loads profiles in both BALB/c and A129 (IFNAR1-/- ) mice upon intraperitoneal (i.p.) inoculation. Remarkably, the CAM/2019 virus exhibited enhanced neurovirulence in neonatal mice compared with CAM/2010, with a 74-fold reduction in the 50% lethal dose (LD50 ). Consistently, CAM/2019 produced higher viral loads in the brains of BALB/c neonatal mice than CAM/2010 did. Sequence alignment showed that the CAM/2019 virus has acquired 12 amino acid substitutions, several of which were found to be associated with neurovirulence. In particular, the CAM/2019 virus shared an A1204T substitution in NS2A with the Thai isolate SI-BKK02 that was isolated from a microcephaly case. Taken together, our results indicate that a ZIKV strain isolated with specific mutations has emerged in Cambodia, highlighting the need for extensive molecular and disease surveillance in Cambodia and other Asian countries.

Neutralization of ARCoV-induced sera against SARS-CoV-2 variants.

ARCoV is a candidate mRNA vaccine encoding receptor-binding domain of SARS-CoV-2. Its safety, tolerability, and immunogenicity profile have been confirmed in the phase 1 clinical trial in China. A multi-regional phase 3 clinical trial is currently underway to test the efficacy of ARCoV (NCT04847102). Here, we tested the cross-neutralization against SARS-CoV-2 variants of concern (VOCs) of a panel of serum samples from participants in the phase 1 clinical trial of ARCoV by pesudo- and authentic SARS-CoV-2. Our data suggest the immunity induced by the ARCoV vaccine reduced but still has significant neutralization against the Alpha and Delta variants. Moreover, ARCoV maintained activity against the Beta variant, despite of its obvious reduction in neutralizing titers. Our findings further support the solid protective neutralization activity against VOCs induced by ARCoV vaccine.

The regulatory function of piRNA/PIWI complex in cancer and other human diseases: The role of DNA methylation.

Piwi-interacting RNAs (piRNAs) are a class of short chain noncoding RNAs that are constituted by 26-30 nucleotides (nt) and can couple with PIWI protein family. piRNAs were initially described in germline cells and are believed to be critical regulators of the maintenance of reproductive line. Increasing evidence has extended our perspectives on the biological significance of piRNAs and indicated that they could still affect somatic gene expression through DNA methylation, chromatin modification and transposon silencing, etc. Many studies have revealed that the dysregulation of piRNAs might contribute to diverse diseases through epigenetic changes represented by DNA methylation and chromatin modification. In this review, we summarized piRNA/PIWI protein-mediated DNA methylation regulation mechanisms and methylation changes caused by piRNA/PIWI proteins in different diseases, especially cancers. Since DNA methylation and inhibitory chromatin marks represented by histone H3 lysine 9 (H3K9) methylation frequently cooperate to silence genomic regions, we also included methylation in chromatin modification within this discussion. Furthermore, we discussed the potential clinical applications of piRNAs as a new type promising biomarkers for cancer diagnosis, as well as the significance of piRNA/PIWI protein-associated methylation changes in treatment, providing disparate insights into the potential applications of them.