Biology subjects

Liu, H.

Publications and source records attributed to Liu, H..

At least 703 records · Page 39Linked to original sources

bioRxiv2021

Single-cell chromatin and gene-regulatory dynamics of mouse nephron progenitors

STRUCTURED ABSTRACTO_ST_ABSBackgroundC_ST_ABSCis-regulatory elements (CREs), such as enhancers and promoters, and their cognate transcription factors play a central role in cell fate specification. Bulk analysis of CREs has provided insights into gene regulation in nephron progenitor cells (NPCs). However, the cellular resolution required to unravel the dynamic changes in regulatory elements associated with cell fate choices remains to be defined. MethodsWe integrated single-cell chromatin accessibility (scATAC-seq) and gene expression (scRNA-seq) in embryonic E16.5 (self-renewing) and postnatal P2 (primed) mouse Six2GFP NPCs. This analysis revealed NPC diversity and identified candidate CREs. To validate these findings and gain additional insights into more differentiated cell types, we performed a multiome analysis of E16.5 and P2 kidneys. ResultsCRE accessibility recovered the diverse states of NPCs and precursors of differentiated cells. Single-cell types such as podocytes, proximal and distal precursors are marked by differentially accessible CREs. Domains of regulatory chromatin as defined by rich CRE-gene associations identified NPC fate-determining transcription factors (TF). Likewise, key TF expression correlates well with its regulon activity. Young NPCs exhibited enrichment in accessible motifs for bHLH, homeobox, and Forkhead TFs, while older NPCs were enriched in AP-1, HNF1, and HNF4 motif activity. A subset of Forkhead factors exhibiting high chromatin activity in podocyte precursors. ConclusionDefining the regulatory landscape of nephrogenesis at single-cell resolution informs the basic mechanisms of nephrogenesis and provides a foundation for future studies in disease states characterized by abnormal nephrogenesis. Significance StatementO_LINephron progenitor cells (NPCs) are a multipotent population giving rise to all cell types of the nephron. At any given time, the NPCs choice to self-renew or differentiate is determined not only by its transcription factor (TF) repertoire but also by the genome accessibility of the cognate cis-regulatory elements. C_LIO_LIUsing single-cell analysis, we demonstrate the heterogeneity of NPCs at the epigenetic level and observe dynamic and cell type-specific changes in chromatin accessibility. Fate-determining TFs harbor domains rich in interactive chromatin that are established prior to gene activation. C_LIO_LIThese findings illustrate the importance of chromatin-based mechanisms in the regulation of nephrogenesis and may have implications for nephron regeneration and repair. C_LI

developmental biology↗

bioRxiv2021

Elevated transcriptional pausing of RNA polymerase II underlies acquired resistance to radiotherapy

As the mainstay modality for many malignancies, particularly inoperable solid tumors such as nasopharyngeal carcinoma (NPC), ionizing radiation (IR) induces a variety of lesions in genomic DNA, evoking a multipronged DNA damage response to interrupt many cellular processes including transcription. The turbulence in transcription, depending on the nature of DNA lesions, encompasses local blockage of RNA polymerase II (RNAPII) near the damage sites, as well as a less understood genome-wide alteration. How the transcriptional change influences the effectiveness of radiotherapy remains unclear. Using a panel of NPC and lung cancer cell lines, we observe increased phosphorylation at serine 5 (pS5) of the RNAPII after IR, indicating an accumulation of paused RNAPII. Remarkably, a similar increase of pS5 is seen in IR-resistant cells. ChIP-seq analysis of RNAPII distribution confirms this increased pausing both in IR-treated and IR-resistant NPC cells, notably on genes involved in radiation response and cell cycle. Accordingly, many of these genes show downregulated transcripts abundance in IR-resistant cells, and individual knockdown some of them such as TP53 and NEK7 endows NPC cells with varying degrees of IR-resistance. Decreasing pS5 of RNAPII and hence tuning down transcriptional pausing by inhibiting CDK7 reverses IR-resistance both in cell culture and xenograft models. Our results therefore uncover an unexpected link between elevated transcriptional pausing and IR-resistance. Given the recurrent NPC tissues display a steady increase in pS5 compared to the paired primary tissues, we suggest that CDK7 inhibitors can be used in combination with radiotherapy to increase sensitivity and thwart resistance.

cancer biology↗

bioRxiv2021

A Phytochrome B-PIF4-MYC2 Module Tunes Secondary Cell Wall Thickening in Response to Shaded Lighting

Secondary cell walls (SCW) in stem xylem cells provide mechanical strength and structural support for growth. SCW thickening is light- regulated and varies under different light growth conditions. Our previous study revealed that blue light enhances SCW thickening through the activity of MYC2 directed by CRYPTOCHROME1 (CRY1) signaling in stem xylary fiber cells. In this study, we demonstrate that the low ratio of red: far-red light (R:FR) of the shaded light condition inhibits SCW thickening in the inflorescence stem of Arabidopsis. Phytochrome B (PHYB) plays a dominant role in perceiving the R:FR balance. Under white and red-light conditions, phyB mutants display thinner SCWs in xylary fibers, but thicker SCWs are deposited in the PHYTOCHROME INTERACTING FACTORS (PIFs) quadruple mutant pif1pif3pif4pif5 (pifq), suggesting involvement of the PHYB-PIFs signaling module in regulating SCW thickening. Interaction of PIF4 with MYC2 affects MYC2 localization in nuclei and inhibits its transactivation activity on the NST1 promoter. Shade conditions mediate the PIF4 interaction with MYC2 to regulate SCW thickening. Genetic analysis confirms that the regulation of SCW thickening by PIFs is dependent on MYC2 function. Together, these data reveal a molecular mechanism for the effect of shaded light inhibition on SCW thickening in stems of Arabidopsis.

plant biology↗

bioRxiv2021

Anatomical and functional connectivity support the existence of a salience network node within the caudal ventrolateral prefrontal cortex

Three large-scale brain networks are considered essential to cognitive flexibility: the ventral and dorsal attention (VAN and DAN) and salience (SN) networks. The ventrolateral prefrontal cortex (vlPFC) is a known component of the VAN and DAN, but there is an important gap in the current knowledge regarding its involvement in the SN. In this study, we used a translational and multimodal approach to fulfill this gap and demonstrate the existence of a SN node within the vlPFC. First, we used tract-tracing methods in non-human primates (NHP) to quantify the anatomic connectivity strength between the different vlPFC areas and the frontal and insular cortices. The strongest connections with the dorsal anterior cingulate cortex (dACC) and anterior insula (AI) locations comprising the two main cortical SN nodes were derived from the caudal area 47/12. This location also has strong axonal projections to subcortical structures of the salience network, including the dorsomedial thalamus, hypothalamus, sublenticular extended amygdala, and periaqueductal gray. Second, we used a seed-based functional connectivity analysis in NHP resting-state functional MRI (rsfMRI) data to validate the caudal area 47/12 as an SN node. Third, we used the same approach in human rsfMRI data to identify a homologous structure in caudal area 47/12, also showing strong connections with the SN cortical nodes, thus confirming the caudal area 47/12 as the SN node in the vlPFC. Taken together, the vlPFC contains nodes for all three cognitive networks, the VAN, DAN, and SN. Thus, the vlPFC is in a position to switch between these three cognitive networks, pointing to a key role as an attentional hub. Its tight additional connections to the orbitofrontal, dorsolateral, and ventral premotor cortices, places the vlPFC at the center for switching behaviors based on environmental stimuli, computing value and cognitive control.

neuroscience↗

bioRxiv2021

A deep learning algorithm for potato tuber hollowheart classification

A novel deep learning algorithm is proposed for hollow heart detection which is an internal tuber defect. Hollow heart is one of many internal defects that decrease the market value of potatoes in the fresh market and food processing sectors. Susceptibility to internal defects like the hollow heart is influenced by genetic and environmental factors so elimination of defect-prone material in potato breeding programs is important. Current methods of evaluation utilize human scoring which is limiting (only collects binary data) relative to the data collection capacity afforded by computer vision or are based upon X-ray transmission techniques that are both expensive and can be hazardous. Automation of defect classification (e.g. hollow heart) from data sets collected using inexpensive, consumer-grade hardware has the potential to increase throughput and reduce bias in public breeding programs. The proposed algorithm consists of ResNet50 as the backbone of the model followed by a shallow fully connected network (FCN). A simple augmentation technique is performed to increase the number of images in the data set. The performance of the proposed algorithm is validated by investigating metrics such as precision and the area under the curve (AUC).

plant biology↗

bioRxiv2021

Nanometer-Scale Imaging of Compartment-Specific Localization and Dynamics of Voltage-Gated Sodium Channels

Membrane excitability and cell-to-cell communication in the brain are tightly regulated by diverse ion channels and receptor proteins localized to distinct membrane compartments. Currently, a major technical barrier in cellular neuroscience is lack of reliable methods to label these membrane proteins and image their sub-cellular localization and dynamics. To overcome this challenge, we devised optical imaging strategies that enable systematic characterization of subcellular composition, relative abundances and trafficking dynamics of membrane proteins at nanometer scales in cultured neurons as well as in the brain. Using these methods, we revealed exquisite developmental regulation of subcellular distributions of voltage-gated sodium channel (VGSC) Nav1.2 and Nav1.6, settling a decade long debate regarding the molecular identity of sodium channels in dendrites. In addition, we discovered a previously uncharacterized trafficking pathway that targets Nav1.2 to unmyelinated fragments in the distal axon. Myelination counteracts this pathway, facilitating the installment of Nav1.6 as the dominant VGSC in the axon. Together, these imaging approaches unveiled compartment-specific trafficking mechanisms underpinning differential membrane distributions of VGSCs and open avenues to decipher how membrane protein localization and dynamics contribute to neural computation in the brain.

neuroscience↗

bioRxiv2021

Structural insights of a highly potent pan-neutralizing SARS-CoV-2 human monoclonal antibody

As the coronavirus disease 2019 (COVID-19) pandemic continues, there is a strong need for highly potent monoclonal antibodies (mAbs) that are resistant against severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) variants of concern (VoCs). Here, we evaluate the potency of a previously described mAb J08 against these variants using cell-based assays and delve into the molecular details of the binding interaction using cryo-EM. We show that mAb J08 has low nanomolar affinity against VoCs, binds high on the receptor binding domain (RBD) ridge and is therefore unaffected by most mutations, and can bind in the RBD-up and -down conformations. These findings further validate the phase II/III human clinical trial underway using mAb J08 as a monoclonal therapy. One Sentence SummaryPotent neutralizing monoclonal antibody J08 binds SARS-CoV-2 spike independent of known escape mutations.

immunology↗

bioRxiv2021

Batch effects removal for microbiome data via conditional quantile regression (ConQuR)

Batch effects in microbiome data arise from differential processing of specimens and can lead to spurious findings and obscure true signals. Most existing strategies for mitigating batch effects rely on approaches designed for genomic analysis, failing to address the zero-inflated and over-dispersed microbiome data. Strategies tailored for microbiome data are restricted to association testing, failing to allow other analytic goals such as visualization. We develop the Conditional Quantile Regression (ConQuR) approach to remove microbiome batch effects using a two-part quantile regression model. It is a fundamental advancement in the field because it is the first comprehensive method that accommodates the complex distributions of microbial read counts, and it generates batch-removed zero-inflated read counts that can be used in and benefit all usual subsequent analyses. We apply ConQuR to real microbiome data sets and demonstrate its state-of-the-art performance in removing batch effects while preserving or even amplifying the signals of interest.

bioinformatics↗

bioRxiv2021

Rapamycin attenuated zinc-induced tau phosphorylation and oxidative stress in animal model: Involvement of dual mTOR/p70S6K and Nrf2/HO-1 pathways

Alzheimers disease is pathologically featured by abnormal accumulation of amyloid-beta plaque, neurofibrillary tangles, oxidative stress, neuroinflammation, and neurodegeneration. Metal dysregulation including excessive zinc released by presynaptic neurons plays an important role in tau pathology and oxidase activation. The activities of mammalian target of rapamycin (mTOR)/ ribosomal S6 protein kinase (p70S6K) are elevated in the brains of patients with Alzheimers disease. Zinc induces tau hyperphosphorylation via mTOR/P70S6K activation in vitro. However, the involvement of mTOR/P70S6K pathway in zinc-induced oxidative stress, tau degeneration, synaptic and cognitive impairment, has not been fully elucidated in vivo. Here we assessed in the effect of pathological concentration of zinc in SH-SY5Y cells by using biochemical assays and immunofluorescence staining. Rats (n = 18, male) were lateral ventricularly-injected with zinc and treated with rapamycin (intraperitoneal injection) for one week and assessed using Morris water maze. Evaluation of the oxidative stress, tau phorsphylation and synaptic impairment were performed using the hippocampus tissue of the rats by biochemical assays and immunofluorescence staining. Results from Morris water maze showed that the capacity of spatial memory is impaired in zinc-treated rats. Zinc sulfate significantly increased the levels of P-mTOR Ser2448, P-p70S6K Thr389, and P-tau Ser356, and decreased levels of Nrf2 and HO{square}1 in SH-SY5Y cells and in zinc-treated rats compared with control groups. Increased expressions of reactive oxygen species were observed in zinc sulfate-induced SH-SY5Y cells as well as in the hippocampus of zinc-injected rats. Rapamycin, an inhibitor of mTOR, rescued the zinc-induced increases in mTOR/p70S6K activations, tau phosphorylation and oxidative stress, as well as Nrf2/HO{square}1 inactivation, cognitive impairment and synaptic impairment reduced the expression of synapse-related proteins in zinc-injected rats. In conclusion, our findings imply that rapamycin prevents zinc-induced cognitive impairment and protects neurons from tau pathology, oxidative stress and synaptic impairment, by decreasing mTOR/p70S6K hyperactivity and increasing Nrf2/HO {square} 1 activity.

neuroscience↗

bioRxiv2021

Nano3P-seq: transcriptome-wide analysis of gene expression and tail dynamics using end-capture nanopore sequencing

RNA polyadenylation plays a central role in RNA maturation, fate, and stability. In response to developmental cues, polyA tail lengths can vary, affecting the translation efficiency and stability of mRNAs. Here, we develop Nanopore 3 end-capture sequencing (Nano3P-seq), a novel method that relies on nanopore cDNA sequencing to simultaneously quantify RNA abundance, tail composition and tail length dynamics at per-read resolution. By employing a template switching-based sequencing protocol, Nano3P-seq can sequence any given RNA molecule from its 3 end, regardless of its polyadenylation status, without the need for PCR amplification or ligation of RNA adapters. We demonstrate that Nano3P-seq captures a wide diversity of RNA biotypes, providing quantitative estimates of RNA abundance and tail lengths in mRNA, lncRNA, sn/snoRNA, scaRNA, and rRNA molecules. We find that, in addition to mRNA and lncRNA, polyA tails can be identified in 16S mitochondrial rRNA in both mouse and zebrafish models. Moreover, we show that mRNA tail lengths are dynamically regulated during vertebrate embryogenesis at an isoform-specific level, correlating with mRNA decay. Finally, we identify non-A bases within polyA tails of various lengths and reveal their distribution during vertebrate embryogenesis. Overall, Nano3P-seq is a simple and robust method for accurately estimating transcript levels, tail lengths, and tail composition heterogeneity in individual reads, with minimal library preparation biases, both in the coding and non-coding transcriptome.

molecular biology↗

bioRxiv2021

Identification of Serum Bridging Molecules that Mediate Human Endothelial Cell Invasion by Candida species

During hematogenously disseminated candidiasis, blood borne fungi must invade the endothelial cells that line the blood vessels to infect the deep tissues. Although Candida albicans, which forms hyphae, readily invades endothelial cells, other medically important species of Candida are poorly invasive in standard in vitro assays. Here, we show that Candida glabrata, Candida tropicalis, Candida parapsilosis, and Candida krusei can bind to vitronectin and high molecular weight kininogen present in human serum. Acting as bridging molecules, vitronectin and kininogen bind to v integrins and the globular C1q receptor (gC1qR), inducing human endothelial cells to endocytose the fungus. This mechanism of endothelial cell invasion is poorly supported by mouse endothelial cells, but can be restored when mouse endothelial cells are engineered to express human gC1qR or v integrin. Overall, these data indicate that bridging molecule-mediated endocytosis is a common pathogenic strategy used by many medically important Candida spp. to invade human vascular endothelial cells. SignificanceThe invasion of vascular endothelial cells is a key step in the pathogenesis of hematogenously disseminated candidiasis. How species of Candida other than C. albicans invade endothelial cells is poorly understood because these fungi are weakly invasive in serum-free media. Here, we demonstrate that C. glabrata and other Candida spp. bind to the serum proteins kininogen and vitronectin, which act as bridging molecules and mediate the adherence and endocytosis of the organisms by endothelial cells. These serum proteins induce endocytosis when they interact with the globular C1q receptor and v integrins on human, but not mouse endothelial cells. Thus, bridging molecule-mediated endocytosis is a common mechanism by which medically important Candida spp. invade human endothelial cells.

microbiology↗

bioRxiv2021

Addressing Enzymatic-Independent Tumor-Promoting Function of NAMPT via PROTAC-Mediated Degradation

The rate-limiting enzyme of salvage pathway for NAD+ synthesis, NAMPT, is aberrantly overexpressed in a variety of tumor cells and is a poor prognosis factor for patient survival. NAMPT plays a major role in tumor cell proliferation, acting concurrently as an NAD+ synthase and unexpectedly, an extracellular ligand for several tumor-promoting signaling pathways. While previous efforts to modulate NAMPT activity were limited to enzymatic inhibitors with low success in clinical studies, protein degradation offers a possibility to simultaneously disrupt NAMPTs enzyme activity and ligand capabilities. Here, we report the development of two highly selective NAMPT-targeted proteolysis-targeting chimeras (PROTACs), which promoted rapid and potent NAMPT degradation in a cereblon-dependent manner in multiple tumor cell lines. Notably, both PROTAC degraders outperform a clinical candidate, FK866, in killing effect on hematological tumor cells. These results emphasize the importance and feasibility of applying PROTACs as a better strategy for targeting proteins like NAMPT with dual tumor-promoting functions, which are not easily achieved by conventional enzymatic inhibitors.

biochemistry↗

bioRxiv2021

Targeted isolation of panels of diverse human broadly neutralizing antibodies against SARS-like viruses

The emergence of current SARS-CoV-2 variants of concern (VOCs) and potential future spillovers of SARS-like coronaviruses into humans pose a major threat to human health and the global economy 1-7. Development of broadly effective coronavirus vaccines that can mitigate these threats is needed 8, 9. Notably, several recent studies have revealed that vaccination of recovered COVID-19 donors results in enhanced nAb responses compared to SARS-CoV-2 infection or vaccination alone 10-13. Here, we utilized a targeted donor selection strategy to isolate a large panel of broadly neutralizing antibodies (bnAbs) to sarbecoviruses from two such donors. Many of the bnAbs are remarkably effective in neutralization against sarbecoviruses that use ACE2 for viral entry and a substantial fraction also show notable binding to non-ACE2-using sarbecoviruses. The bnAbs are equally effective against most SARS-CoV-2 VOCs and many neutralize the Omicron variant. Neutralization breadth is achieved by bnAb binding to epitopes on a relatively conserved face of the receptor binding domain (RBD) as opposed to strain-specific nAbs to the receptor binding site that are commonly elicited in SARS-CoV-2 infection and vaccination 14-18. Consistent with targeting of conserved sites, select RBD bnAbs exhibited in vivo protective efficacy against diverse SARS-like coronaviruses in a prophylaxis challenge model. The generation of a large panel of potent bnAbs provides new opportunities and choices for next-generation antibody prophylactic and therapeutic applications and, importantly, provides a molecular basis for effective design of pan-sarbecovirus vaccines.

immunology↗

bioRxiv2021

Heterologous synapsis in C. elegans is regulated by meiotic double-strand breaks and crossovers

Alignment of the parental chromosomes during meiotic prophase is key to the formation of genetic exchanges, or crossovers, and consequently to the successful production of gametes. In almost all studied organisms, alignment involves synapsis: the assembly of a conserved inter-chromosomal interface called the synaptonemal complex (SC). While the SC usually synapses homologous sequences, it can assemble between heterologous sequences. However, little is known about the regulation of heterologous synapsis. Here we study the dynamics of heterologous synapsis in the nematode C. elegans. We characterize two experimental scenarios: SC assembly onto a folded-back chromosome that cannot pair with its homologous partner; and synapsis of pseudo-homologs, a fusion chromosome partnering with an unfused chromosome half its size. We observed elevated levels of heterologous synapsis when the number of meiotic double-strand breaks or crossovers were reduced, indicating that the promiscuity of synapsis is regulated by break formation or repair. By manipulating the levels of breaks and crossovers, we infer both chromosome-specific and nucleus-wide regulation on heterologous synapsis. Finally, we identify differences between the two conditions, suggesting that attachment to the nuclear envelope plays a role in regulating heterologous synapsis.

cell biology↗

bioRxiv2021

Interfered Chromosome Pairing Promotes Meiosis Instability of Autotetraploid Arabidopsis by High Temperatures

Alterations of environmental temperature affect multiple meiosis processes in flowering plants. Polyploid plants derived from whole genome duplication (WGD) have enhanced genetic plasticity and tolerance to environmental stress, but meanwhile face a challenge for organization and segregation of doubled chromosome sets. In this study, we investigated the impact of increased environmental temperature on male meiosis in autotetraploid Arabidopsis thaliana. Under low to mildly-increased temperatures (5-28{degrees}C), irregular chromosome segregation universally takes place in synthesized autotetraploid Columbia-0 (Col-0). Similar meiosis lesions occur in autotetraploid rice (Oryza sativa L.) and allotetraploid canola (Brassica napus cv. Westar), but not in evolutionary-derived hexaploid wheat (Triticum aestivum). As temperature increases to extremely high, chromosome separation and tetrad formation are severely disordered due to univalent formation caused by suppressed crossing-over. We found a strong correlation between tetravalent formation and successful chromosome pairing, both of which are negatively correlated with temperature elevation, suggesting that increased temperature interferes with crossing-over prominently by impacting homolog pairing. Besides, we showed that loading irregularities of axis proteins ASY1 and ASY4 co-localize on the chromosomes of syn1 mutant, and the heat-stressed diploid and autotetraploid Col-0, revealing that heat stress affects lateral region of synaptonemal complex (SC) by impacting stability of axis. Moreover, we showed that chromosome axis and SC in autotetraploid Col-0 are more sensitive to increased temperature than that of diploid Arabidopsis. Taken together, our study provide evidence suggesting that WGD without evolutionary and/or natural adaption negatively affects stability and thermal tolerance of meiotic recombination in Arabidopsis thaliana.

plant biology↗

bioRxiv2021

The exosomes derived from urine of premature infants target MAPK8 via miR-30a-5p to protect cisplatin-induced acute kidney injury in mice

AimAcute kidney injury (AKI), a global public health issue, not only causes millions of deaths every year, but is also a susceptible factor for chronic kidney disease (CKD). Nephrotoxic drugs are an important cause of AKI. There is still a lack of effective and satisfactory prevention method in clinical practice. This study investigated the protective effect of the exosomes derived from urine of premature infants on cisplatin-induced acute kidney injury. MethodsIsolation of exosomes from fresh urine of premature infants: The characteristics of exosomes were determined by flow cytometry, transmission electron microscopy and Western blotting. A C57BL/6 mice model of cisplatin-induced acute kidney injury was established. The mice in the experimental group were given 100ug exosomes dissolved in 200ul solution. The mice in the control group were given normal saline (200ul). These treatments were performed 24 hours after AKI was induced by intraperitoneal injection of cisplatin. To evaluate renal function, blood was drawn 24 hours after AKI model was established and serum creatinine (sCr) was measured. The mice were euthanized 72 hours after exosome treatment. The kidneys were collected for pathological examination, RNA and protein extraction, and the evaluation of renal tubular damage and apoptosis. In the in-vitro experiment, human renal cortex/proximal tubular cells (HK2) was induced by cisplatin to assess the protective ability of the exosomes derived from urine of premature infants. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western Blotting were used to evaluate the effect of exosomes treatment on the apoptosis of HK2 cells induced by cisplatin. Exosome microRNA sequencing technology and bioinformatics analysis method were applied to investigate the miRNAs enriched in exosomes and their target genes. The dual luciferase gene reporter system was used to detect the interaction of target genes. ResultsTreatment of exosomes derived from urine of premature infants could decrease the level of serum creatinine and the apoptosis of renal tubular cell, inhibit the infiltration of inflammatory cell, protect mice from acute kidney injury induced by cisplatin and reduce mortality. In addition, miR-30a-5p was the most abundant miRNA in the exosomes derived from urine of premature infants. It protected HK2 cells from cisplatin-induced apoptosis by targeting and down-regulating the 3UTR of mitogen-activated protein kinases (MAPK8) mRNA. ConclusionsAccording to our results, the exosomes derived from urine of premature infants alleviated cisplatin-induced acute kidney injury in mice and inhibited the apoptosis of human proximal tubular cells (HK2) induced by cisplatin in vitro. MiR-30a-5p in exosomes inhibited cisplatin-induced MAPK activation, ameliorated apoptosis, and protected renal function. The exosomes derived from urine of premature infants provided a promising acellular therapy for AKI.

molecular biology↗

bioRxiv2021

Air-nanobubbles ineffective to reduce pathogenic bacteria in fresh and brackish waters

Nanobubble (NB) technology has been hailed as a novel way to disinfect water. Previous studies suggested that when NBs collapse, they create shock waves that result in OH- free radicals, which can damage cells, including bacteria. In this study, we investigated, through a series of 11 experiments, the potential use of air nanobubbles (128 {+/-} 44 nm, mean {+/-} SD) to reduce the concentration of various pathogenic bacteria including Aeromonas hydrophila, A. veronii, Vibrio parahaemolyticus, and Streptococcus agalactiae under controlled, tank-based laboratory conditions. Despite the high number of nanobubbles continuously added to a relatively small volume of water in experimental tanks (50-100 L), we did not observe a consistent or significant decrease in bacteria that would control disease outbreaks. Although most of the experiments were conducted in fresh water on A. hydrophila, results were consistent across fresh and brackish water experiments, Gram-negative and Gram-positive bacteria, and a range of nanobubble concentrations. This study suggests air nanobubbles on their own are inadequate to significantly reduce high levels of pathogenic bacteria in water. We propose to explore other gases for improving the disinfection properties of this technology. SIGNIFICANCE STATEMENTAir nanobubbles did not sufficiently reduce the level of bacteria in laboratory experiments.

microbiology↗

bioRxiv2021

The Lambda variant of SARS-CoV-2 has a better chance than the Delta variant to escape vaccines

The newly emerging variants of SARS-CoV-2 from India (Delta variant) and South America (Lambda variant) have led to a higher infection rate of either vaccinated or unvaccinated people. We found that sera from Pfizer-BioNTech vaccine remain high reactivity toward the receptor binding domain (RBD) of Delta variant while it drops dramatically toward that of Lambda variant. Interestingly, the overall titer of antibodies of Pfizer-BioNTech vaccinated individuals drops 3-fold after 6 months, which could be one of major reasons for breakthrough infections, emphasizing the importance of potential third boost shot. While a therapeutic antibody, Bamlanivimab, decreases binding affinity to Delta variant by ~20 fold, it fully lost binding to Lambda variant. Structural modeling of complexes of RBD with human receptor, Angiotensin Converting Enzyme 2 (ACE2), and Bamlanivimab suggest the potential basis of the change of binding. The data suggest possible danger and a potential surge of Lambda variant in near future.

immunology↗