Zika virus infection leads to hormone deficiencies of the hypothalamic-pituitary-gonadal axis and diminished fertility in mice.

IMPORTANCE: Zika virus (ZIKV) infection in pregnant women during the third trimester can cause neurodevelopmental delays and cryptorchidism in children without microcephaly. However, the consequences of congenital ZIKV infection on fertility in these children remain unclear. Here, using an immunocompetent mouse model, we reveal that congenital ZIKV infection can cause hormonal disorders of the hypothalamic-pituitary-gonadal axis, leading to reduced fertility and decreased sexual preference. Our study has for the first time linked the hypothalamus to the reproductive system and social behaviors after ZIKV infection. Although the extent to which these observations in mice translate to humans remains unclear, these findings did suggest that the reproductive health and hormone levels of ZIKV-exposed children should receive more attention to improve their living quality.

Identification and Analysis of the MIR399 Gene Family in Grapevine Reveal Their Potential Functions in Abiotic Stress.

MiR399 plays an important role in plant growth and development. The objective of the present study was to elucidate the evolutionary characteristics of the MIR399 gene family in grapevine and investigate its role in stress response. To comprehensively investigate the functions of miR399 in grapevine, nine members of the Vvi-MIR399 family were identified based on the genome, using a miRBase database search, located on four chromosomes (Chr 2, Chr 10, Chr 15, and Chr 16). The lengths of the Vvi-miR399 precursor sequences ranged from 82 to 122 nt and they formed stable stem-loop structures, indicating that they could produce microRNAs (miRNAs). Furthermore, our results suggested that the 2 to 20 nt region of miR399 mature sequences were relatively conserved among family members. Phylogenetic analysis revealed that the Vvi-MIR399 members of dicots (Arabidopsis, tomato, and sweet orange) and monocots (rice and grapevine) could be divided into three clades, and most of the Vvi-MIR399s were closely related to sweet orange in dicots. Promoter analysis of Vvi-MIR399s showed that the majority of the predicted cis-elements were related to stress response. A total of 66.7% (6/9) of the Vvi-MIR399 promoters harbored drought, GA, and SA response elements, and 44.4% (4/9) of the Vvi-MIRR399 promoters also presented elements involved in ABA and MeJA response. The expression trend of Vvi-MIR399s was consistent in different tissues, with the lowest expression level in mature and young fruits and the highest expression level in stems and young leaves. However, nine Vvi-MIR399s and four target genes showed different expression patterns when exposed to low light, high light, heat, cold, drought, and salt stress. Interestingly, a putative target of Vvi-MIR399 targeted multiple genes; for example, seven Vvi-MIR399s simultaneously targeted VIT_213s0067g03280.1. Furthermore, overexpression of Vvi_MIR399e and Vvi_MIR399f in Arabidopsis enhanced tolerance to drought compared with wild-type (WT). In contrast, the survival rate of Vvi_MIR399d-overexpressed plants were zero after drought stress. In conclusion, Vvi-MIR399e and Vvi-MIR399f, which are related to drought tolerance in grapevine, provide candidate genes for future drought resistance breeding.

Zika Virus Infection in the Ovary Induces a Continuously Elevated Progesterone Level and Compromises Conception in Interferon Alpha/Beta Receptor-Deficient Mice.

Zika virus (ZIKV) belongs to mosquito-borne flaviviruses. Unlike other members in the family, ZIKV can be sexually transmitted, and the female genital tracts are susceptible to ZIKV. However, the impact of ZIKV infection on nonpregnant female reproductive health is not understood. In this study, we investigated the effects of ZIKV infection on the ovary by using nonpregnant female interferon α/ß receptor-deficient (Ifnar1-/-) mice. The results showed that the ovary supported ZIKV replication, and the granulosa and theca cells of antral follicles were susceptible. ZIKV replication in situ significantly reduced the numbers of antral follicles, aggravated follicular atresia, and disrupted folliculogenesis. Notably, ZIKV replication in the ovary caused disordered ovarian steroidogenesis manifested by decreased expression of key enzymes linked to sex hormone synthesis, including the cytochrome P450 17A1 (CYP17A1) and aromatase (CYP19A1). Further, we observed that ZIKV infection disrupted the estrous cycle and thus prolonged the time to conceive. More importantly, although ZIKV RNA could not be detected at 3 months postinfection, damaged ovarian structure and dysfunction were also observed. Taken together, our study demonstrates that ZIKV infection in nonpregnant female mice cause ovarian damage and dysfunction, even long after ZIKV clearance. These data provide important information to understand the effects of ZIKV infection in female reproductive tissues and basic evidence for further studies. IMPORTANCE Zika virus (ZIKV), a flavivirus, is primarily transmitted by mosquito bites. But it can also be transmitted vertically and sexually. Although ZIKV-associated Guillain-Barré syndrome and microcephaly have drawn great attention, there have been few studies on the potential effects of ZIKV on the genital tract of nonpregnant females. This study investigated the effects of ZIKV on the ovaries in mice. We found that ZIKV replicated in the ovary and the granulosa and theca cells of antral follicles were susceptible. ZIKV replication in situ significantly damaged ovarian structure and function and disrupted folliculogenesis. Notably, ZIKV infection further disrupted the estrous cycle and prolonged the time to conceive in mice by causing disordered ovarian steroidogenesis. These effects were observed in both the acute phase and the recovery phase after viral elimination. Overall, the new findings provide important additions to make out the potential adverse impacts of ZIKV on reproductive health in females.

Rasmussen's encephalitis is characterized by relatively lower production of IFN-ß and activated cytotoxic T cell upon herpes viruses infection.

BACKGROUND: The etiology of Rasmussen's encephalitis (RE), a rare chronic neurological disorder characterized by CD8+ T cell infiltration and unihemispheric brain atrophy, is still unknown. Various human herpes viruses (HHVs) have been detected in RE brain, but their contribution to RE pathogenesis is unclear. METHODS: HHVs infection and relevant immune response were compared among brain tissues from RE, temporal lobe epilepsy (TLE) and traumatic brain injury (TBI) patients. Viral antigen or genome, CD8+ T cells, microglia and innate immunity molecules were analyzed by immunohistochemical staining, DNA dot blot assay or immunofluorescence double staining. Cytokines were measured by multiplex flow cytometry. Cell apoptosis was visualized by TUNEL staining. Viral infection, immune response and the severity of unihemispheric atrophy were subjected to correlation analysis. RESULTS: Antigens of various HHVs were prevalent in RE and TLE brains, and the cumulative viral score of HHVs positively correlated with the unihemispheric atrophy in RE patients. CD8+ T cells infiltration were observed in both RE and TLE brains and showed co-localization with HHV antigens, but their activation, as revealed by Granzyme B (GZMB) release and apoptosis, was found only in RE. In comparison to TLE, RE brain tissues contained higher level of inflammatory cytokines, but the interferon-ß level, which was negatively correlated with cumulative viral score, was relatively lower. In line with this, the DNA sensor STING and IFI16, rather than other innate immunity signaling molecules, were insufficiently activated in RE. CONCLUSIONS: Compared with TBI, both RE and TLE had prevalently HHV infection and immune response in brain tissues. However, in comparison to TLE, RE showed insufficient activation of antiviral innate immunity but overactivation of cytotoxic T cells. Our results show the relatively lower level of antiviral innate immunity and overactivation of cytotoxic T cells in RE cases upon HHV infection, the overactivated T cells might be a compensate to the innate immunity but the causative evidence is lack in our study and need more investigation in the future.

S100A4+ macrophages facilitate zika virus invasion and persistence in the seminiferous tubules via interferon-gamma mediation.

Testicular invasion and persistence are features of Zika virus (ZIKV), but their mechanisms are still unknown. Here, we showed that S100A4+ macrophages, a myeloid macrophage subpopulation with susceptibility to ZIKV infection, facilitated ZIKV invasion and persistence in the seminiferous tubules. In ZIKV-infected mice, S100A4+ macrophages were specifically recruited into the interstitial space of testes and differentiated into interferon-γ-expressing M1 macrophages. With interferon-γ mediation, S100A4+ macrophages down-regulated Claudin-1 expression and induced its redistribution from the cytosol to nucleus, thus increasing the permeability of the blood-testis barrier which facilitated S100A4+ macrophages invasion into the seminiferous tubules. Intraluminal S100A4+ macrophages were segregated from CD8+ T cells and consequently helped ZIKV evade cellular immunity. As a result, ZIKV continued to replicate in intraluminal S100A4+ macrophages even when the spermatogenic cells disappeared. Deficiencies in S100A4 or interferon-γ signaling both reduced ZIKV infection in the seminiferous tubules. These results demonstrated crucial roles of S100A4+ macrophages in ZIKV infection in testes.

Epidemiological and clinical characteristics of the chikungunya outbreak in Ruili City, Yunnan Province, China.

Chikungunya fever is an acute infectious disease caused by the chikungunya virus (CHIKV) that is characterized by fever, rash, and joint pain. CHIKV has infected millions of people in Africa, Asia, America, and Europe since it re-emerged in the Indian Ocean region in 2004. Here, we report an outbreak of Chikungunya fever that occurred in Ruili of Yunnan Province, a city located on the border between China and Myanmar, in September 2019. The outbreak lasted for three months from September to December. Overall, 112 cases were confirmed by a real-time reverse-transcription polymerase chain reaction in the Ruili People's Hospital, and they showed apparent temporal, spatial, and population aggregation. Among them, 91 were local cases distributed in 19 communities of Ruili City, and 21 were imported cases. The number of female patients was higher than that of male patients, and most patients were between 20 and 60 years old. The main clinical manifestations included joint pain (91.96%), fever (86.61%), fatigue (58.04%), chills (57.14%), rash (48.21%), headache (39.29%), and so forth. Biochemical indexes revealed increased C-reactive protein (63.39%), lymphopenia (57.17%), increased hemoglobin (33.04%), neutrophilia (28.57%), and thrombocytopenia (16.07%). Phylogenetic analysis of the complete sequences indicated that the CHIKV strains in this outbreak belonged to the Indian Ocean clade of the East/Central/South African genotype. We speculated that this chikungunya outbreak might be caused by CHIKV-infected persons returning from Myanmar, and provided a reference for the formulation of effective treatment and prevention measures.

Axl Deficiency Promotes the Neuroinvasion of Japanese Encephalitis Virus by Enhancing IL-1α Production from Pyroptotic Macrophages.

Japanese encephalitis virus (JEV) is a flavivirus that causes Japanese encephalitis (JE), which has an unclear pathogenesis. Despite vaccination, thousands of deaths attributed to JE are reported annually. In this study, we report that mice deficient for Axl, a receptor tyrosine kinase that plays multiple roles in flaviviral infection, displayed greater mortality upon JEV infection. The effect of Axl deficiency on JEV infection was mediated by markedly elevated serum interleukin-1α (IL-1α) levels, which devastated the blood-brain-barrier and promoted viral neuroinvasion within 24 h postinfection. Using an in situ infection model, we showed that dead macrophages were the primary source of observed increased serum IL-1α levels. Axl deficiency enhanced cell death and caused pyroptosis in 80% of JEV-infected macrophages by disrupting phosphatidylinositol 3-kinase (PI3K)-Akt signaling. Intriguingly, the primary effector released by pyroptotic macrophages in our model was IL-1α rather than IL-1ß. Finally, we assessed the effect of an IL-1α antagonist and demonstrated that it effectively prevented the incidence of JE. Our results indicate that Axl plays a protective role in JEV infection, identify IL-1α released by pyroptotic macrophages as a crucial factor promoting JEV neuroinvasion, and suggest that an IL-1α antagonist may be a candidate for JE therapy.IMPORTANCE Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus that causes Japanese encephalitis (JE), the most commonly diagnosed viral encephalitis worldwide. The fatality rate of JE is 20%, and nearly half of the surviving patients develop neuropsychiatric sequelae. Axl is a receptor tyrosine kinase that plays multiple roles in flaviviral infections. Currently, the involvement of Axl in JEV infection remains enigmatic. In this study, we demonstrate that Axl impedes the pathogenesis of severe JE in mice by maintaining blood-brain-barrier (BBB) integrity and restricting viral neuroinvasion. Furthermore, serum IL-1α is a key mediator of this process and is primarily released by JEV-infected pyroptotic macrophages to elicit BBB breakdown, while an IL-1α antagonist can effectively reduce the incidence of severe JE. Our work uncovers the protective role of Axl in antagonizing severe JE and shows that the use of an IL-1α antagonist may be a promising tactic to prevent severe JE.

Effect of the Rho GTPase inhibitor-1 on the entry of dengue serotype 2 virus into EAhy926 cells.

Dengue virus (DV) is the most rapidly spreading arbovirus in the world. Our previous studies indicated that Rac1, a kind of Rho GTPase, was related with the increased vascular permeability in DV infection. However, the molecular mechanisms that regulate the activity of the Rac1 pathway during DV infection is not fully understood yet. Recently, Rho-specific guanine nucleotide dissociated inhibitors (Rho GDIs), as a pivotal upstream regulator of Rho GTPase, attract our attention. To identify the role of GDI-1 in DV2 infection, the expression of GDI in Eahy926 cells was detected. Moreover, a GDI-1 down-regulated cell line was constructed to explore the correlation between GDI-1 and Rac1 and to further evaluate the function of GDI in DV life cycle. Our results indicated that DV2 infection could up-regulate GDI-1 expression, and down-regulation of GDI enhanced the activity of Rac1. In addition, down-regulated GDI-1 significantly inhibited all steps of DV2 replication cycle. GDI-1 plays an important role in DV2 infection via negatively regulating the activation of the Rac1-actin pathway. These results not only contribute to our further understanding of the pathogenesis of severe dengue but also provide further insight into the development of antiviral drugs.

T cell immunity rather than antibody mediates cross-protection against Zika virus infection conferred by a live attenuated Japanese encephalitis SA14-14-2 vaccine.

Zika virus (ZIKV) and Japanese encephalitis virus (JEV) are closely related to mosquito-borne flaviviruses. Japanese encephalitis (JE) vaccine SA14-14-2 has been in the Chinese national Expanded Program on Immunization since 2007. The recent recognition of severe disease syndromes associated with ZIKV, and the identification of ZIKV from mosquitoes in China, prompts an urgent need to investigate the potential interaction between the two. In this study, we showed that SA14-14-2 is protective against ZIKV infection in mice. JE vaccine SA14-14-2 triggered both Th1 and Th2 cross-reactive immune responses to ZIKV; however, it was cellular immunity that predominantly mediated cross-protection against ZIKV infection. Passive transfer of immune sera did not result in significant cross-protection but did mediate antibody-dependent enhancement in vitro, though this did not have an adverse impact on survival. This study suggests that the SA14-14-2 vaccine can protect against ZIKV through a cross-reactive T cell response. This is vital information in terms of ZIKV prevention or precaution in those ZIKV-affected regions where JEV circulates or SA14-14-2 is in widespread use, and opens a promising avenue to develop a novel bivalent vaccine against both ZIKV and JEV. KEY POINTS: • JEV SA14-14-2 vaccine conferred cross-protection against ZIKV challenge in mice. • T cell immunity rather than antibody mediated the cross-protection. • It provides important information in terms of ZIKV prevention or precaution.

Japanese encephalitis virus prM-E antigen immunization conferred protection against challenge by four different serotypes of Dengue viruses in mice.

Dengue virus (DENV) and Japanese encephalitis virus (JEV) are closely related mosquito-borne flaviviruses. Together, they caused most arthropod-borne diseases in the world. Previously, we had demonstrated that both live attenuated and inactivated JE vaccines elicited cross-protection against DENV infection, and a DNA vaccine candidate expressing JEV prM-E protein (named pCAG-JME) could provide effective protection against JEV infection in mice. In this study, we examined whether the same pCAG-JME could elicit cross-protection against DENV infection. Our results showed that pCAG-JME indeed induced cross-reactive antibodies and cross-protection against four different serotypes of DENV in mice. Interestingly, pCAG-JME-immunized mice also generated both Th1 and Th2 responses when stimulated by all four different serotypes of DENV antigens. Moreover, cross-primed CD8+ T cell response was also detected following the stimulation of DENV proteins using intracellular cytokine staining. In addition, sera from pCAG-JME-immunized mice significantly reduced the mortality caused by DENV2 infection in severe combination immunodeficiency mouse. These results suggest that both JE and DENV cross-reactive antibodies and cross-primed T cells might play important roles in the cross-protection. The findings of this study also indicate a possibility of developing novel multivalent genetically engineered vaccines against both JEV and DENV.

Transcriptome analysis of Valsa mali reveals its response mechanism to the biocontrol actinomycete Saccharothrix yanglingensis Hhs.015.

BACKGROUND: Apple canker is a devastating branch disease caused by Valsa mali (Vm). The endophytic actinomycete Saccharothrix yanglingensis Hhs.015 (Sy Hhs.015) can effectively inhibit the growth of Vm. To reveal the mechanism, by which Vm respond to Sy Hhs.015, the transcriptome of Vm was analyzed using RNA-seq technology. RESULTS: Compared with normal growing Vm in the control group, 1476 genes were significantly differentially expressed in the Sy Hhs.015's treatment group, of which 851 genes were up-regulated and 625 genes were down-regulated. Combined gene function and pathway analysis of differentially expressed genes (DEGs) revealed that Sy Hhs.015 affected the carbohydrate metabolic pathway, which is utilized by Vm for energy production. Approximately 82% of the glycoside hydrolase genes were down-regulated, including three pectinase genes (PGs), which are key pathogenic factors. The cell wall structure of Vm was disrupted by Sy Hhs.015 and cell wall-related genes were found to be down-regulated. Of the peroxisome associated genes, those encoding catalase (CAT) and superoxide dismutase (SOD) which scavenge reactive oxygen species (ROS), as well as those encoding AMACR and ACAA1 which are related to the ß-oxidation of fatty acids, were down-regulated. MS and ICL, key genes in glyoxylate cycle, were also down-regulated. In response to the stress of Sy Hhs.015 exposure, Vm increased amino acid metabolism to synthesize the required nitrogenous compounds, while alpha-keto acids, which involved in the TCA cycle, could be used to produce energy by deamination or transamination. Retinol dehydrogenase, associated with cell wall dextran synthesis, and sterol 24-C-methyltransferase, related to cell membrane ergosterol synthesis, were up-regulated. The genes encoding glutathione S-transferase, (GST), which has antioxidant activity and ABC transporters which have an efflux function, were also up-regulated. CONCLUSION: These results show that the response of Vm to Sy Hhs.015 exposure is a complicated and highly regulated process, and provide a theoretical basis for both clarifying the biocontrol mechanism of Sy Hhs.015 and the response of Vm to stress.

Axl is not an indispensable factor for Zika virus infection in mice.

Recently, Zika virus (ZIKV) outbreak has been associated with a sharp increase in cases of Guillain-Barré syndrome and severe fetal abnormalities. However, the mechanism underlying the interaction of ZIKV with host cells is not yet clear. Axl, a receptor tyrosine kinase, is postulated as a receptor for ZIKV entry; however, its in vivo role during ZIKV infection and its impact on the outcome of the disease have not been fully characterized and evaluated. Moreover, there are contradictory results on its involvement in ZIKV infection. Here we utilized Axl-deficient mice (Axl-/-) and their littermates (Axl+/-) to study the in vivo role of Axl in ZIKV infection. Our results showed that both Axl+/- and Axl-/- suckling mice supported the replication of ZIKV and presented clinical manifestations. No significant difference has been found between Axl-deficient mice and their littermates in terms of the survival rate, clinical manifestations, viral load, ZIKV distribution and histopathological changes in major organs. These results therefore indicate that Axl is not an indispensable factor for ZIKV infection in mice.

Immunization with electroporation enhances the protective effect of a DNA vaccine candidate expressing prME antigen against dengue virus serotype 2 infection.

PURPOSE: We aimed to use the dengue virus (DV) serotype 2 as a proof of principal for testing the efficacy of a DNA vaccine candidate via in vivo electroporation in mice and rabbits prior to the development of a tetravalent vaccine. METHODS: Different dosages of DNA pVAX1-D2ME encoding DV2 prME genes were vaccinated in mice via intramuscular injection or in vivo electroporation, immune responses and protection were determined. In DNA-vaccinated rabbits via electroporation, antibody titer and protein expression were tested. RESULTS: In mice, 50µg of pVAX1-D2ME via electroporation elicited effective anti-DV2 responses and conferred significant protection against DV2 challenge. Moreover, anti-DV2 IgG and neutralizing antibodies were successfully induced in rabbits immunized with pVAX1-D2ME via electroporation and the expression of the interest protein was observed at local sites. CONCLUSIONS: Enhanced immunogenicity and protective effect conferred by pVAX1-D2ME via electroporation show great promise for the development of a dengue tetravalent DNA vaccine.

Saccharothrix yanglingensis Strain Hhs.015 Is a Promising Biocontrol Agent on Apple Valsa Canker.

Apple Valsa canker (AVC), caused by Valsa mali, results in a serious and persistent disease problem for apple production in China and is difficult to control by chemical and agricultural measures. In this study, we determined the inhibitory effects of an endophytic actinomycete Saccharothrix yanglingensis strain Hhs.015 on V. mali under laboratory and the field conditions. Fermentation broth (FB) of Hhs.015 significantly inhibited conidial germination and mycelial growth, causing malformed and dysfunctional fungal structures. Detached apple (Malus domestica 'Fuji') twigs smeared with FB before V. mali inoculation significantly reduced lesion development, especially sporulation. In the orchard trials conducted from 2010 to 2013, trunks and branches smeared with FB three times significantly reduced the number of new lesions. In addition, wounds after lesion surgery coated with FB also enhanced callus formation and significantly improved the cure rate. The results showed that S. yanglingensis Hhs.015 is effective against AVC in orchards. Thus, S. yanglingensis Hhs.015 can be further developed as an effective biocontrol agent for more sustainable management of AVC.

Immunocompetent mouse models revealed that S100A4+ monocytes/macrophages facilitate long-term Zika virus infection in the testes.

During its global epidemic, Zika virus (ZIKV) attracted widespread attention due to its link with various severe neurological symptoms and potential harm to male fertility. However, the understanding of how ZIKV invades and persists in the male reproductive system is limited due to the lack of immunocompetent small animal models. In this study, immunocompetent murine models were generated by using anti-IFNAR antibody blocked C57BL/6 male mice and human STAT2 (hSTAT2) knock in (KI) male mice. After infection, viral RNA could persist in the testes even after the disappearance of viremia. We also found a population of ZIKV-susceptible S100A4+ monocytes/macrophages that were recruited into testes from peripheral blood and played a crucial role for ZIKV infection in the testis. By using single-cell RNA sequencing, we also proved that S100A4+ monocytes/macrophages had a great impact on the microenvironment of ZIKV-infected testes, thus promoting ZIKV-induced testicular lesions. In conclusion, this study proposed a novel mechanism of long-term ZIKV infection in the male reproductive system.

Mice with type I interferon signaling deficiency are prone to epilepsy upon HSV-1 infection.

Viral encephalitis continues to be a significant public health concern. In our previous study, we discovered a lower expression of antiviral factors, such as IFN-ß, STING and IFI16, in the brain tissues of patients with Rasmussen's encephalitis (RE), a rare chronic neurological disorder often occurred in children, characterized by unihemispheric brain atrophy. Furthermore, a higher cumulative viral score of human herpes viruses (HHVs) was also found to have a significant positive correlation with the unihemispheric atrophy in RE. Type I IFNs (IFN-I) signaling is essential for innate anti-infection response by binding to IFN-α/ß receptor (IFNAR). In this study, we infected WT mice and IFNAR-deficient A6 mice with herpes simplex virus 1 (HSV-1) via periocular injection to investigate the relationship between IFN-I signaling and HHVs-induced brain lesions. While all mice exhibited typical viral encephalitis lesions in their brains, HSV-induced epilepsy was only observed in A6 mice. The gene expression matrix, functional enrichment analysis and protein-protein interaction network revealed four gene models that were positively related with HSV-induced epilepsy. Additionally, ten key genes with the highest scores were identified. Taken together, these findings indicate that intact IFN-I signaling can effectively limit HHVs induced neural symptoms and brain lesions, thereby confirming the positive correlation between IFN-I signaling repression and brain atrophy in RE and other HHVs encephalitis.

The impact of the COVID-19 pandemic on dietary behaviors among school-age children, adolescents, and young adults: a systematic review and meta-analysis.

CONTEXT: The COVID-19 pandemic has had a global impact on food security and nutrition, both in the short and long term. The influence on school-age children, adolescents, and young adults may be particularly significant and long-lasting. OBJECTIVE: This systematic review and meta-analysis aimed to quantify the impact of the COVID-19 pandemic on dietary habits among school-age children, adolescents, and young adults worldwide. DATA SOURCES: PubMed, Web of Science, and Embase were searched from inception to October 5, 2023. DATA EXTRACTION: We included observational studies published in English that reported dietary quality scores and dietary intake quantities during and before the COVID-19 pandemic among school-age children, adolescents, and young adults. We included a total of 22 cohort studies and 20 cross-sectional studies of high or moderate quality. DATA ANALYSIS: We conducted a meta-analysis, expressing dietary quality scores and dietary intake quantities as standardized mean differences (SMD) with 95% confidence intervals (CIs). For studies with low heterogeneity, we used a fixed-effects model; otherwise, we applied a random-effects model. The Newcastle-Ottawa Scale was employed by 2 reviewers independently to evaluate methodological quality. The analysis indicated that, overall, juice intake increased (SMD = 0.12, 95% CI: 0.04 to 0.20), while alcohol consumption reduced during the COVID-19 pandemic (SMD = -0.28, 95% CI: -0.47 to -0.08). However, the age-stratified results varied. Among school-age children, intake of fruit, dairy products, sugar, and juice increased. Adolescents showed an increase in meal frequency and vegetable intake. Young adults showed reduced carbohydrate and alcohol intakes, while protein and dairy product intakes increased, based on limited included studies. CONCLUSION: Dietary changes in school-age children from before to during the pandemic were mixed, while dietary behavior changes in adolescents and young adults tended to be more positive. Considering the lasting effects of negative dietary behaviors, attention should be given to addressing the increased sugar and juice intakes. It is also crucial that caregivers and researchers monitor whether positive dietary behaviors will rebound after returning to normal study and life. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42023420923.

Neutrophil infiltration leads to fetal growth restriction by impairing the placental vasculature in DENV-infected pregnant mice.

BACKGROUND: Dengue virus (DENV) infection during pregnancy increases the risk of adverse fetal outcomes, which has become a new clinical challenge. However, the underlying mechanism remains unknown. METHODS: The effect of DENV-2 infection on fetuses was investigated using pregnant interferon α/ß receptor-deficient (Ifnar1-/-) mice. The histopathological changes in the placentas were analyzed by morphological techniques. A mouse inflammation array was used to detect the cytokine and chemokine profiles in the serum and placenta. The infiltration characteristics of inflammatory cells in the placentas were evaluated by single-cell RNA sequencing. FINDINGS: Fetal growth restriction observed in DENV-2 infection was mainly caused by the destruction of the placental vasculature rather than direct damage from the virus in our mouse model. After infection, neutrophil infiltration into the placenta disrupts the expression profile of matrix metalloproteinases, which leads to placental dysvascularization and insufficiency. Notably, similar histopathological changes were observed in the placentas from DENV-infected puerperae. INTERPRETATION: Neutrophils play key roles in placental histopathological damage during DENV infection, which indicates that interfering with aberrant neutrophil infiltration into the placenta may be an important therapeutic target for adverse pregnancy outcomes in DENV infection. FUNDING: The National Key Research and Development Plans of China (2021YFC2300200-02 to J.A., 2019YFC0121905 to Q.Z.C.), the National Natural Science Foundation of China (NSFC) (U1902210 and 81972979 to J. A., 81902048 to Z. Y. S., and 82172266 to P.G.W.), and the Support Project of High-level Teachers in Beijing Municipal Universities in the Period of 13th Five-year Plan, China (IDHT20190510 to J. A.).

Mice 3D testicular organoid system as a novel tool to study Zika virus pathogenesis.

Zika virus (ZIKV) poses a serious threat to global public health due to its close relationship with neurological and male reproductive damage. However, deficiency of human testicular samples hinders the in-depth research on ZIKV-induced male reproductive system injury. Organoids are relatively simple in vitro models, which could mimic the pathological changes of corresponding organs. In this study, we constructed a 3D testicular organoid model using primary testicular cells from adult BALB/c mice. Similar to the testis, this organoid system has a blood-testis barrier (BTB)-like structure and could synthesize testosterone. ZIKV tropism of testicular cells and ZIKV-induced pathological changes in testicular organoid was also similar to that in mammalian testis. Therefore, our results provide a simple and reproducible in vitro testicular model for the investigations of ZIKV-induced testicular injury.

Characterization and identification of grapevine heat stress-responsive microRNAs revealed the positive regulated function of vvi-miR167 in thermostability.

High temperature stress is one of the primary abiotic stresses that restrict fruit tree production. Grapevine (Vitis vinifera) with high economic value throughout the world is a cultivated fruit crop, and its growth and development is often influenced by high temperature stress. Studying the heat stress-response mechanism of grapevine has great significance for understanding the acclimation to heat stress. In this study, we identified a series of heat stress responsive miRNAs and analyzed their function during the heat tolerance response. CK (control group, 25 °C) and heat treatment stress (TS, 45 °C) small RNA (sRNA) libraries were constructed and sequenced by high-throughput sequencing in 'Thompson seedless' grapevine. 873 known-miRNAs and 86 novel-miRNAs were identified, of which 88 known and three novel miRNAs were expressed differentially under heat stress. 322 genes were predicted to be targeted by the miRNAs. Eight selected miRNAs and its targets were confirmed by real time quantitative PCR (RT - qPCR), indicating that these "miRNA - target" were responsive to heat stress. In addition, most of the predicted target genes were negatively regulated by corresponding miRNAs. Gene function and pathway analyses indicated that these genes probably play crucial roles in heat stress tolerance. Vvi-miR167b transiently overexpression in grapevine leaves decreased target gene vvARF6, vvARF6-like and vvARF8 expression. The function of vvi-miR167 was verified by ectopic transformation in Arabidopsis thaliana, and the heat tolerance in transgenic lines was enhanced significantly, suggesting that the vvi-miR167 plays a positive regulatory role in grape thermostability. Comparison of miRNA expression patterns between heat treatment stress and CK can help elucidate the heat stress response and resistance mechanisms in grapes. In conclusion, these results gave us useful information to better understand the heat stress-response during domestication as well as for breeding new cultivars with heat stress resistance in fruit trees.