Reactivation of cytomegalovirus and bloodstream infection and its impact on early survival after allogeneic haematopoietic stem cell transplantation: a multicentre retrospective study.

Cytomegalovirus reactivation (CMVr) and bloodstream infections (BSI) are the most common infectious complications in patients after allogeneic haematopoietic stem cell transplantation (allo-HSCT). Both are associated with great high morbidity whilst the BSI is the leading cause of mortality. This retrospective study evaluated the incidence of CMVr and BSI, identified associated risk factors, assessed their impact on survival in allo-HSCT recipients during the first 100 days after transplantation. The study comprised 500 allo-HSCT recipients who were CMV DNA-negative and CMV IgG-positive before allo-HSCT. Amongst them, 400 developed CMVr and 75 experienced BSI within 100 days after allo-HSCT. Multivariate regression revealed that graft failure and acute graft-versus-host disease were significant risk factors for poor prognosis, whereas CMVr or BSI alone were not. Amongst all 500 patients, 56 (14%) developed both CMVr and BSI in the 100 days after HSCT, showing significantly reduced 6-month overall survival (p = 0.003) and long-term survival (p = 0.002). Specifically, in the initial post-transplant phase (within 60 days), BSI significantly elevate mortality risk, However, patients who survive BSI during this critical period subsequently experience a lower mortality risk. Nevertheless, the presence of CMVr in patients with BSI considerably diminishes their long-term survival prospects. This study provides real-world data on the impact of CMVr and BSI following transplantation on survival, particularly in regions such as China, where the prevalence of CMV IgG-positivity is high. The findings underscore the necessity for devising and executing focused prevention and early management strategies for CMVr and BSI to enhance outcomes for allo-HSCT recipients.

Effects of BBIBP-CorV vaccine on gut microbiota and short-chain fatty acids in mice exposed to bis (2-ethylhexyl) phthalate and dioctyl terephthalate.

As the COVID-19 pandemic has progressed, increasing evidences suggest that the gut microbiota may play a crucial role in the effectiveness of SARS-CoV-2 vaccine. Thus, this study was aimed at investigating the influence of SARS-CoV-2 vaccine on the gut microbiota and short-chain fatty acids (SCFAs) of organisms exposed to environmental contaminants, i.e., plasticizers: phthalate esters. We found that in mice, exposure to dioctyl terephthalate (DOTP) and bis -2-ethylhexyl phthalate (DEHP) decreased the blood glucose level and white fat weight, induced inflammatory responses, caused damage to liver and intestinal tissues, and disrupted the gut microbiota composition and SCFAs metabolism. Specifically, the Bacteroidetes phylum was positively correlated with BBIBP-CorV vaccine, while acetic acid was negatively associated with the vaccine. Interestingly, the BBIBP-CorV vaccine somewhat alleviated tissue inflammation and reduced the contents of acetic acid and propionic acid in mice exposed to DEHP and DOTP. These findings were confirmed by a fecal microbiota transplantation assay. Overall, this study revealed that exposure to DEHP and DOTP adversely affects the gut microbiota and SCFAs, while the BBIBP-CorV vaccine can protect mice against these effects. This work highlighted the relationship between BBIBP-CorV vaccination, gut microbiome composition, and responses to plasticizers, which may facilitate the development and risk assessment of SARS-CoV-2 vaccines and environmental contaminants on microbiota health.

SlZIP11 mediates zinc accumulation and sugar storage in tomato fruits.

Background: Zinc (Zn) is a vital micronutrient essential for plant growth and development. Transporter proteins of the ZRT/IRT-like protein (ZIP) family play crucial roles in maintaining Zn homeostasis. Although the acquisition, translocation, and intracellular transport of Zn are well understood in plant roots and leaves, the genes that regulate these pathways in fruits remain largely unexplored. In this study, we aimed to investigate the function of SlZIP11 in regulating tomato fruit development. Methods: We used Solanum lycopersicum L. 'Micro-Tom' SlZIP11 (Solanum lycopersicum) is highly expressed in tomato fruit, particularly in mature green (MG) stages. For obtaining results, we employed reverse transcription-quantitative polymerase chain reaction (RT-qPCR), yeast two-hybrid assay, bimolecular fluorescent complementation, subcellular localization assay, virus-induced gene silencing (VIGS), SlZIP11 overexpression, determination of Zn content, sugar extraction and content determination, and statistical analysis. Results: RT-qPCR analysis showed elevated SlZIP11 expression in MG tomato fruits. SlZIP11 expression was inhibited and induced by Zn deficiency and toxicity treatments, respectively. Silencing SlZIP11 via the VIGS technology resulted in a significant increase in the Zn content of tomato fruits. In contrast, overexpression of SlZIP11 led to reduced Zn content in MG fruits. Moreover, both silencing and overexpression of SlZIP11 caused alterations in the fructose and glucose contents of tomato fruits. Additionally, SlSWEEET7a interacted with SlZIP11. The heterodimerization between SlSWEET7a and SlZIP11 affected subcellular targeting, thereby increasing the amount of intracellularly localized oligomeric complexes. Overall, this study elucidates the role of SlZIP11 in mediating Zn accumulation and sugar transport during tomato fruit ripening. These findings underscore the significance of SlZIP11 in regulating Zn levels and sugar content, providing insights into its potential implications for plant physiology and agricultural practices.

Identification of novel compound heterozygous ZFP36L2 variants implicated in oocyte maturation defects and female infertility.

PURPOSE: To explore the pathogenesis of oocyte maturation defects. METHODS: Whole exome sequencing was conducted to identify potential variants, which were then confirmed within the pedigree through Sanger sequencing. The functional characterization of the identified variants responsible for the disease, including their subcellular localization, protein levels, and interactions with other proteins, was verified through transient transfection in HeLa cells in vitro. Additionally, we employed real-time RT-PCR and single-cell RNA sequencing to examine the impact of ZFP36L2 pathogenic variants on mRNA metabolism in both HeLa cells and mouse or human oocytes. RESULTS: A novel compound heterozygous variant in ZFP36L2 (c.186T > G, p.His62Gln and c.869 C > T, p.Pro290Leu) was discovered in a patient with oocyte maturation defects. Our findings indicate that these variants lead to compromised binding capacity of the ZFP36L2-CONT6L complex and impaired mRNA degradation in HeLa cells and mouse oocytes. Furthermore, we characterized the changes in the human oocyte transcriptome associated with ZFP36L2 variants, with a particular emphasis on cell division, mitochondrial function, and ribosome metabolism. CONCLUSIONS: This study broadens the mutation spectrum of ZFP36L2 and constitutes the first report of human oocyte transcriptome alterations linked to ZFP36L2 variants. In conjunction with existing knowledge of ZFP36L2, our research lays the groundwork for genetic counseling aimed at addressing female infertility.

GmDFB1, an ARM-repeat superfamily protein, regulates floral organ identity through repressing siRNA- and miRNA-mediated gene silencing in soybean.

The development of flowers in soybean (Glycine max) is essential for determining the yield potential of the plant. Gene silencing pathways are involved in modulating flower development, but their full elucidation is still incomplete. Here, we conducted a forward genetic screen and identified an abnormal flower mutant, deformed floral bud1-1 (Gmdfb1-1), in soybean. We mapped and identified the causal gene, which encodes a member of the armadillo (ARM)-repeat superfamily. Using small RNA sequencing (sRNA-seq), we found an abnormal accumulation of small interfering RNAs (siRNAs) and microRNA (miRNAs) in the Gmdfb1 mutants. We further demonstrated that GmDFB1 interacts with the RNA exosome cofactor SUPER KILLER7 (GmSKI7). Additionally, GmDFB1 interacts with the PIWI domain of ARGONAUTE 1 (GmAGO1) to inhibit the cleavage efficiency on the target genes of sRNAs. The enhanced gene silencing mediated by siRNA and miRNA in the Gmdfb1 mutants leads to the downregulation of their target genes associated with flower development. This study revealed the crucial role of GmDFB1 in regulating floral organ identity in soybean probably by participating in two distinct gene silencing pathways.

MicroRNA and Gut Microbiota Alter Intergenerational Effects of Paternal Exposure to Polyethylene Nanoplastics.

Nanoplastics (NPs), as emerging contaminants, have been shown to cause testicular disorders in mammals. However, whether paternal inheritance effects on offspring health are involved in NP-induced reproductive toxicity remains unclear. In this study, we developed a mouse model where male mice were administered 200 nm polyethylene nanoparticles (PE-NPs) at a concentration of 2 mg/L through daily gavage for 35 days to evaluate the intergenerational effects of PE-NPs in an exclusive male-lineage transmission paradigm. We observed that paternal exposure to PE-NPs significantly affected growth phenotypes and sex hormone levels and induced histological damage in the testicular tissue of both F0 and F1 generations. In addition, consistent changes in sperm count, motility, abnormalities, and gene expression related to endoplasmic reticulum stress, sex hormone synthesis, and spermatogenesis were observed across paternal generations. The upregulation of microRNA (miR)-1983 and the downregulation of miR-122-5p, miR-5100, and miR-6240 were observed in both F0 and F1 mice, which may have been influenced by reproductive signaling pathways, as indicated by the RNA sequencing of testis tissues and quantitative real-time polymerase chain reaction findings. Furthermore, alterations in the gut microbiota and subsequent Spearman correlation analysis revealed that an increased abundance of Desulfovibrio (C21_c20) and Ruminococcus (gnavus) and a decreased abundance of Allobaculum were positively associated with spermatogenic dysfunction. These findings were validated in a fecal microbiota transplantation trial. Our results demonstrate that changes in miRNAs and the gut microbiota caused by paternal exposure to PE-NPs mediated intergenerational effects, providing deeper insights into mechanisms underlying the impact of paternal inheritance.

Lack of T04C9.1, the Homologue of Mammalian APPL2, Leads to Premature Ageing and Shortens Lifespan in Caenorhabditis elegans.

Ageing has been identified as an independent risk factor for various diseases; however, the physiological basis and molecular changes related to ageing are still largely unknown. Here, we show that the level of APPL2, an adaptor protein, is significantly reduced in the major organs of aged mice. Knocking down APPL2 causes premature ageing of human umbilical vein endothelial cells (HUVECs). We find that a lack of T04C9.1, the homologue of mammalian APPL2, leads to premature ageing, slow movements, lipid deposition, decreased resistance to stresses, and shortened lifespan in Caenorhabditis elegans (C. elegans), which are associated with decreased autophagy. Activating autophagy by rapamycin or inhibition of let-363 suppresses the age-related alternations, impaired motility, and shortened lifespan of C. elegans, which are reversed by knocking down autophagy-related genes. Our work provides evidence that APPL2 and its C. elegans homologue T04C9.1 decrease with age and reveals that a lack of T04C9.1 bridges autophagy decline and ageing in C. elegans.

TCERG1L hypermethylation is a risk factor of diabetic retinopathy in Chinese children with type 1 diabetes.

AIM: To identify the differential methylation sites (DMS) and their according genes associated with diabetic retinopathy (DR) development in type 1 diabetes (T1DM) children. METHODS: This study consists of two surveys. A total of 40 T1DM children was included in the first survey. Because no participant has DR, retina thinning was used as a surrogate indicator for DR. The lowest 25% participants with the thinnest macular retinal thickness were included into the case group, and the others were controls. The DNA methylation status was assessed by the Illumina methylation 850K array BeadChip assay, and compared between the case and control groups. Four DMS with a potential role in diabetes were identified. The second survey included 27 T1DM children, among which four had DR. The methylation patterns of the four DMS identified by 850K were compared between participants with and without DR by pyrosequencing. RESULTS: In the first survey, the 850K array revealed 751 sites significantly and differentially methylated in the case group comparing with the controls (|Δß|>0.1 and Adj.P<0.05), and 328 of these were identified with a significance of Adj.P<0.01. Among these, 319 CpG sites were hypermethylated and 432 were hypomethylated in the case group relative to the controls. Pyrosequencing revealed that the transcription elongation regulator 1 like (TCERG1L, cg07684215) gene was hypermethylated in the four T1DM children with DR (P=0.018), which was consistent with the result from the first survey. The methylation status of the other three DMS (cg26389052, cg25192647, and cg05413694) showed no difference (all P>0.05) between participants with and without DR. CONCLUSION: The hypermethylation of the TCERG1L gene is a risk factor for DR development in Chinese children with T1DM.

Widespread 2013-2020 decreases and reduction challenges of organic aerosol in China.

High concentrations of organic aerosol (OA) occur in Asian countries, leading to great health burdens. Clean air actions have resulted in significant emission reductions of air pollutants in China. However, long-term nation-wide trends in OA and their causes remain unknown. Here, we present both observational and model evidence demonstrating widespread decreases with a greater reduction in primary OA than in secondary OA (SOA) in China during the period of 2013 to 2020. Most of the decline is attributed to reduced residential fuel burning while the interannual variability in SOA may have been driven by meteorological variations. We find contrasting effects of reducing NOx and SO2 on SOA production which may have led to slight overall increases in SOA. Our findings highlight the importance of clean energy replacements in multiple sectors on achieving air-quality targets because of high OA precursor emissions and fluctuating chemical and meteorological conditions.

Gut Microbiota Affects Host Fitness of Fall Armyworm Feeding on Different Food Types.

The fall armyworm (FAW), Spodoptera frugiperda, seriously threatens food and cash crops. Maize, wheat, and even rice damage by FAWs have been reported in many areas of China. It is urgent to clarify the mechanism which FAWs adapt to different feeding hosts and develop effective control technologies. Two-sex life tables and 16s rDNA sequencing were used to determine the host fitness and gut microbial diversity of FAWs when fed four different food types. Considering the life history parameters, pupa weight, and nutrient utilization indexes, the host fitness of FAWs when fed different food types changed in descending order as follows: artificial diet, maize, wheat, and rice. The gut microbial composition and the diversity of FAWs when fed different food types were significantly different, and those changes were driven by low-abundant bacteria. The gut microbes of FAWs that were fed with maize had the highest diversity. The functions of the gut microbes with significant abundance differences were enriched in nutrient and vitamin metabolism and other pathways that were closely related to host adaptation. Furthermore, we identified five genera (Acinetobacter, Variovorax, Pseudomonas, Bacillus, and Serratia) and one genus (Rahnella) that were positively and negatively correlated with the host fitness, respectively. This study revealed the possible role of gut microbes in the host adaptation of FAWs.

The adipose-neural axis is involved in epicardial adipose tissue-related cardiac arrhythmias.

Dysfunction of the sympathetic nervous system and increased epicardial adipose tissue (EAT) have been independently associated with the occurrence of cardiac arrhythmia. However, their exact roles in triggering arrhythmia remain elusive. Here, using an in vitro coculture system with sympathetic neurons, cardiomyocytes, and adipocytes, we show that adipocyte-derived leptin activates sympathetic neurons and increases the release of neuropeptide Y (NPY), which in turn triggers arrhythmia in cardiomyocytes by interacting with the Y1 receptor (Y1R) and subsequently enhancing the activity of the Na+/Ca2+ exchanger (NCX) and calcium/calmodulin-dependent protein kinase II (CaMKII). The arrhythmic phenotype can be partially blocked by a leptin neutralizing antibody or an inhibitor of Y1R, NCX, or CaMKII. Moreover, increased EAT thickness and leptin/NPY blood levels are detected in atrial fibrillation patients compared with the control group. Our study provides robust evidence that the adipose-neural axis contributes to arrhythmogenesis and represents a potential target for treating arrhythmia.

Generation of FOXJ1-EGFP knock-in reporter human embryonic stem cell line, WAe001-A-2D, using CRISPR/Cas9-based gene targeting.

Forkhead box protein J1 (FOXJ1), a member of the forkhead family, is an important transcription factor regulating multiciliated cell differentiation and motile ciliogenic program. Here, we established a FOXJ1- EGFP knock-in human embryonic stem cell (hESC) line by inserting a P2A-EGFP gene cassette of FOXJ1 using CRISPR/Cas9 system. The reporter cell line retained a normal karyotype, expressed comparable pluripotent marker genes, and maintained differentiation potential. This reporter cell line enables live identification of multiciliated cells during the general lung differentiation and will be a valuable tool for studying the multiciliated cell differentiation, ciliogenesis and mechanism of related pulmonary diseases.

FGF7 enhances the expression of ACE2 in human islet organoids aggravating SARS-CoV-2 infection.

The angiotensin-converting enzyme 2 (ACE2) is a primary cell surface viral binding receptor for SARS-CoV-2, so finding new regulatory molecules to modulate ACE2 expression levels is a promising strategy against COVID-19. In the current study, we utilized islet organoids derived from human embryonic stem cells (hESCs), animal models and COVID-19 patients to discover that fibroblast growth factor 7 (FGF7) enhances ACE2 expression within the islets, facilitating SARS-CoV-2 infection and resulting in impaired insulin secretion. Using hESC-derived islet organoids, we demonstrated that FGF7 interacts with FGF receptor 2 (FGFR2) and FGFR1 to upregulate ACE2 expression predominantly in ß cells. This upregulation increases both insulin secretion and susceptibility of ß cells to SARS-CoV-2 infection. Inhibiting FGFR counteracts the FGF7-induced ACE2 upregulation, subsequently reducing viral infection and replication in the islets. Furthermore, retrospective clinical data revealed that diabetic patients with severe COVID-19 symptoms exhibited elevated serum FGF7 levels compared to those with mild symptoms. Finally, animal experiments indicated that SARS-CoV-2 infection increased pancreatic FGF7 levels, resulting in a reduction of insulin concentrations in situ. Taken together, our research offers a potential regulatory strategy for ACE2 by controlling FGF7, thereby protecting islets from SARS-CoV-2 infection and preventing the progression of diabetes in the context of COVID-19.

Distinct global brain connectivity alterations in depressed adolescents with subthreshold mania and the relationship with processing speed: Evidence from sBEAD Cohort.

BACKGROUND: Bipolar disorder (BD) is a progressive condition. Investigating the neuroimaging mechanisms in depressed adolescents with subthreshold mania (SubMD) facilitates the early identification of BD. However, the global brain connectivity (GBC) patterns in SubMD patients, as well as the relationship with processing speed before the onset of full-blown BD, remain unclear. METHODS: The study involved 72 SubMD, 77 depressed adolescents without subthreshold mania (nSubMD), and 69 gender- and age-matched healthy adolescents (HCs). All patients underwent a clinical follow-up ranging from six to twelve months. We calculated the voxel-based graph theory analysis of the GBC map and conducted the TMT-A test to measure the processing speed. RESULTS: Compared to HCs and nSubMD, SubMD patients displayed distinctive GBC index patterns: GBC index decreased in the right Medial Superior Frontal Gyrus (SFGmed.R)/Superior Frontal Gyrus (SFG) while increased in the right Precuneus and left Postcentral Gyrus. Both patient groups showed increased GBC index in the right Inferior Temporal Gyrus. An increased GBC value in the right Supplementary Motor Area was exclusively observed in the nSubMD-group. There were opposite changes in the GBC index in SFGmed.R/SFG between two patient groups, with an AUC of 0.727. Additionally, GBC values in SFGmed.R/SFG exhibited a positive correlation with TMT-A scores in SubMD-group. LIMITATIONS: Relatively shorter follow-up duration, medications confounding, and modest sample size. CONCLUSION: These findings suggest that adolescents with subthreshold BD have specific impairments patterns at the whole brain connectivity level associated with processing speed impairments, providing insights into early identification and intervention strategies for BD.

Hypoxia macrophage-derived exosomal miR-26b-5p targeting PTEN promotes the development of keloids.

Background: Hypoxia is the typical characteristic of keloids. The development of keloids is closely related to the abnormal phenotypic transition of macrophages. However, the role of exosomal microRNAs (miRNAs) derived from hypoxic macrophages in keloids remains unclear. This study aimed to explore the role of hypoxic macrophage-derived exosomes (HMDE) in the occurrence and development of keloids and identify the critical miRNA. Methods: The expression of CD206+ M2 macrophage in keloids and normal skin tissues was examined through immunofluorescence. The polarization of macrophages under a hypoxia environment was detected through flow cytometry. The internalization of macrophage-derived exosomes in human keloid fibroblasts (HKFs) was detected using a confocal microscope. miRNA sequencing was used to explore the differentially expressed miRNAs in exosomes derived from the normoxic and hypoxic macrophage. Subsequently, the dual-luciferase reporter assay verified that phosphatase and tension homolog (PTEN) was miR-26b-5p's target. The biological function of macrophage-derived exosomes, miR-26b-5p and PTEN were detected using the CCK-8, wound-healing and Transwell assays. Western blot assay was used to confirm the miR-26b-5p's underlying mechanisms and PTEN-PI3K/AKT pathway. Results: We demonstrated that M2-type macrophages were enriched in keloids and that hypoxia treatment could polarize macrophages toward M2-type. Compared with normoxic macrophages-derived exosomes (NMDE), HMDE promote the proliferation, migration and invasion of HKFs. A total of 38 differential miRNAs (18 upregulated and 20 downregulated) were found between the NMDE and HMDE. miR-26b-5p was enriched in HMDE, which could be transmitted to HKFs. According to the results of the functional assay, exosomal miR-26b-5p produced by macrophages facilitated HKFs' migration, invasion and proliferation via the PTEN-PI3K/AKT pathway. Conclusions: The highly expressed miR-26b-5p in HMDE promotes the development of keloids via the PTEN-PI3K/AKT pathway.

CenterADNet: Infrared Video Target Detection Based on Central Point Regression.

Infrared video target detection is a fundamental technology within infrared warning and tracking systems. In long-distance infrared remote sensing images, targets often manifest as circular spots or even single points. Due to the weak and similar characteristics of the target to the background noise, the intelligent detection of these targets is extremely complex. Existing deep learning-based methods are affected by the downsampling of image features by convolutional neural networks, causing the features of small targets to almost disappear. So, we propose a new infrared video weak-target detection network based on central point regression. We focus on suppressing the image background by fusing the different features between consecutive frames with the original image features to eliminate the background's influence. We also employ high-resolution feature preservation and incorporate a spatial-temporal attention module into the network to capture as many target features as possible and improve detection accuracy. Our method achieves superior results on the infrared image weak aircraft target detection dataset proposed by the National University of Defense Technology, as well as on the simulated dataset generated based on real-world observation. This demonstrates the efficiency of our approach for detecting weak point targets in infrared continuous images.

A global progressive image secret sharing scheme under multi-group joint management.

Diverging from traditional secret sharing schemes, group secret sharing schemes enable the recovery of secret information through collaborative efforts among groups. Existing schemes seldom consider the issue of the secrecy level of image information between different groups. Therefore, we propose a global progressive image secret sharing scheme under multi-group joint management. For inter-group relations, multiple groups with different priority levels are constructed using the approach of bit-polar decomposition. In this arrangement, higher-level groups obtain clearer secret image information. For intra-group relations, a participant-weighted secret sharing scheme is constructed based on Chinese Remainder Theorem and Birkhoff interpolation, in which the participants' secret sub-shares are reusable. During the recovery process, the sub-images can be recovered within the intragroup with the corresponding level. Groups collaborate through lightweight overlay operations to obtain different layers of secret images, achieving a global progressive effect. Analysis results show that the scheme is both secure and practical for group secret sharing.

RABC1, an Arabidopsis RAB18 regulates binding and subsequent detachment of autophagosomes from the ER in autophagy.

Macroautophagy/autophagy is a strategy cells use to cope with detrimental conditions, e.g. nutrient deficiency. Phagophores, the precursors to autophagosomes, are initiated and expanded on the endoplasmic reticulum (ER). However, how phagophores and completed autophagosomes are linked to the ER remains incompletely understood. We recently unveiled a RAB GTPase-based linkage between the two structures. RABC1 is a plant member of RABC/RAB18 GTPases. Our biochemical and microscopy data indicated that RABC1 promotes autophagy in response to nutrient starvation, but not under ER stress. Under nutrient-starvation conditions, active RABC1 interacts with ATG18a on the ER, controlling the association of ATG18a to the ER. Subsequently, active RABC1 is turned off allowing expanded phagophores or autophagosomes to detach from the ER. Our work identifies a RAB GTPase-mediated autophagy process in plant cells, opening a door for improving crop productivity in the changing environment.