Biology subjects

Hou, F.

Publications and source records attributed to Hou, F..

12 recordsLinked to original sources

bioRxiv2026

Density-dependent facilitation of livestock by small mammal ecosystem engineers

Small mammals and large herbivores have co-evolved in grasslands for millions of years, yet how they interplay remains unclear. Although large herbivores can significantly affect the smaller ones, the reversal effect is largely unknown. On the Qinghai-Tibetan Plateau, plateau pikas (Ochotona curzoniae) are often considered pests that compete with livestock at high densities. Using field experiments, we show that the presence of pikas facilitates weight gains of yaks (Bos grunniens) by improving vegetation composition at a moderate density level. Compared to the pika-present treatment, pika removal dramatically increased cover of the poisonous Stellera forbs by two-fold, reducing the abundance and protein content of palatable grasses and sedges, yak foraging efficiency, and yak weight gain by up to 42%. Notably, we found a humped relationship between yak weight gains and pika burrow densities in the pika-present plots; the facilitative effect of pikas on yaks was highest at about 200 burrows/ha, but shifted to a competitive effect at pika densities exceeding 400 burrows/ha. These results provide the first empirical evidence that maintaining a moderate density of small mammalian herbivores can benefit growth performance of livestock by improving vegetation composition. Our study highlights the significance of moderate populations of ecosystem-engineering small mammals in sustaining pastoral productivity in rangelands.

ecology↗

bioRxiv2026

End-to-end bimodal anti-counterfeiting by informational DNA nanoparticles

The superior stealth properties and high information density make DNA a sought-after candidate in the field of molecular steganography. Here, we developed the InfinMark end-to-end DNA steganography framework for anti-counterfeiting applications by combining the characteristics of both the Internet of Things (IoT) and DNA-of-Things (DoT). InfinMark includes five modules: Information Transcoding, Fingerprint Writing, Nano-encapsulation, Invisible Marking, and Multi-level Rapid Authentication. It ensures precise anti-counterfeiting information reading and writing through a dynamic DNA-compatible transcoding algorithm, achieves seamless embedding by developing scalable nanoparticle manufacture methods, and supports cross-scenario on-site verification, ultimately granting it comprehensive anti-counterfeiting capabilities spanning from source labeling to terminal tracing. By addressing the bottlenecks in IoT and DoT integration, lifecycle tracking, as well on-site product authentication, this research constructs a full-chain bimodal anti-counterfeiting system, thereby showcasing the practical application of informational DNA nanoparticles in various aspects of production and daily life.

synthetic biology↗

bioRxiv2025

Primate-specific adaptation of Ku protects transcriptomic integrity by suppressing Alu-mediated alternative splicing

Accurate pre-mRNA splicing is essential for the transfer of genetic information but faces unique challenge in higher primates due to the massive expansion of intronic Alu elements1-3. While studying Ku, the Ku70/Ku80 heterodimer best known for initiating non-homologous end-joining (NHEJ) by encircling DNA ends4, we discovered that Ku expression increased markedly during primate evolution in parallel with Alu expansion5. Ku binds double-stranded RNA (dsRNA) stem-loops, including those at the antisense Alu (asAlu) elements within introns5. Here, we show that Ku-depletion in human cells has a broad impact on splicing largely independent of cell-cycle states, NHEJ, or innate immune signaling, significantly affecting ~8-10% of quantifiable alternative splicing events. Mechanistically, Ku directly binds exonic asAlu to prevent their aberrant inclusion and binds asAlu within inverted-repeat Alu (irAlu) pairs flanking canonical exons to prevent exon skipping6. Among human tissues, Ku expression in the brain is consistently ~50% lower, correlating with more permissive expression of Alu-derived splice variants, particularly those encoding mitochondrial proteins and RNA-binding factors. Correspondingly, heterozygous Ku loss in patient causes developmental delay, neurological dysfunction, and acidosis. Together our findings identified Ku as a critical suppressor of Alu-associated alternative splicing co-opted during evolution with implications for primate brain function and human disease.

molecular biology↗

bioRxiv2024

Observation of Higher-Order Assemblies Controlled by Protein One-dimensional Movement

RIG-I-like receptors (RLRs) detect cytosolic viral RNAs and initiate innate immune response. MDA5 is an RLR that recognizes viral long double-stranded RNA (dsRNA). The central helicase and C-terminal domains of MDA5 form a ring-like clamp around dsRNA, and its activation requires the oligomerization of N-terminal caspase activation and recruitment domains (CARDs). Another RLR, LGP2, lacks CARDs but plays essential roles in MDA5 signaling. However, the mechanisms underlying MDA5 CARDs assembly and the collaborative mechanics between MDA5 and LGP2 remain largely unresolved. Here we found the MDA5 ring-like clamp operates as an ATP-hydrolysis-driven motor, with the self-assembly of its CARDs strictly suppressed by the protein one-dimensional (1D) translocation along dsRNA. LGP2 recognizes a mobile MDA5 and inhibits the motors movement, thereby allowing MDA5 CARDs to assemble into oligomers that can further interact with downstream components. These findings highlight how RLR sensors orchestrate higher-order assemblies through 1D movement to direct immune response.

biophysics↗

bioRxiv2022

Novel mRNA vaccines encoding Monkeypox virus M1R and A35R protect mice from a lethal virus challenge

The outbreak of Monkeypox virus infection urgently need effective vaccines. However, the vaccines so far approved are all based on whole-virus, which raises safety concerns. MRNA vaccines has demonstrated its high efficacy and safety against SARS-Cov-2 infection. Here, we developed three mRNA vaccines encoding Monkeypox proteins M1R and A35R, including A35R-M1R fusions (VGPox1 and VGPox 2) and a combination of encapsulated full-length mRNAs for A35R and M1R (VGPox 3). All three vaccines induced anti-A35R total IgGs as early as day 7 following a single vaccination. However, only VGPox 1 and 2 produced anti-M1R total IgGs at early dates following vaccination while VGPox 3 did not show significant anti-M1R antibody till day 35. Similar results were also found in neutralizing antibodies and T cell immune response. However, all mRNA vaccine groups completely protected mice from a lethal dose virus challenge and effectively cleared virus in lungs. Collectively, our results indicate that the novel mRNA vaccines coding for a fusion protein of A35R and M1R had a better anti-virus immunity than co-expression of the two individual proteins. The mRNA vaccines are highly effective and can be an alternative to the current whole-virus vaccines to defend Monkeypox virus infection.

immunology↗

bioRxiv2022

Heterologous boost with mRNA vaccines against SARS-CoV-2 Delta/Omicron variants following an inactivated whole-virus vaccine

The coronavirus SARS-CoV-2 has mutated quickly and caused significant global damage. This study characterizes two mRNA vaccines ZSVG-02 (Delta) and ZSVG-02-O (Omicron BA.1), and associating heterologous prime-boost strategy following the prime of a most widely administrated inactivated whole-virus vaccine (BBIBP-CorV). The ZSVG-02-O induces neutralizing antibodies that effectively cross-react with Omicron subvariants following an order of BA.1>BA.2>BA.4/5. In naive animals, ZSVG-02 or ZSVG-02-O induce humoral responses skewed to the vaccines targeting strains, but cellular immune responses cross-react to all variants of concern (VOCs) tested. Following heterologous prime-boost regimes, animals present comparable neutralizing antibody levels and superior protection across all VOCs. Single-boost only generated ancestral and omicron dual-responsive antibodies, probably by "recall" and "reshape" the prime immunity. New Omicron-specific antibody populations, however, appeared only following the second boost with ZSVG-02-O. Overall, our results support a heterologous boost with ZSVG-02-O, providing the best protection against current VOCs in inactivated virus vaccine- primed populations.

molecular biology↗

bioRxiv2021

Integrative interactome and ubiquitinome analyses reveal multiple regulatory pathways targeted by ICP0 in HSV-1 infected neuronal cells

Herpes simplex virus 1 (HSV-1) is a neurotropic virus that can undergo both productive and latent infection in neurons. ICP0 is an HSV-1 E3 ubiquitin ligase crucial for productive infection and reactivation from latency. However, its targets have not been systematically investigated in neuronal cells. After confirming the importance of ICP0 in HSV-1 neuronal replication using an ICP0-null virus, we identified many ICP0-interacting proteins in infected neuronal and non-neuronal cells by mass-spectrometry-based interactome analysis. Co-immunoprecipitation assays validated ICP0 interactions with ACOT8, C1QBP, OTUD4, SNX9 and VIM in both Neuro-2a and 293T cells. Overexpression and knockdown experiments showed that SNX9 restricted replication of the ICP0-null but not wild-type virus in Neuro-2a cells. Ubiquitinome analysis by immunoprecipitating the trypsin digested ubiquitin reminant followed by mass spectrometry identified numerous candidate ubiquitination substrates of ICP0 in infected Neuro-2a cells, among which OTUD4 and VIM were novel substrates confirmed to be ubiquitinated by transfected ICP0 in Neuro-2a cells despite no evidence of their degradation by ICP0. Expression of OTUD4 was induced independently of ICP0 during HSV-1 infection. Overexpressed OTUD4 enhanced type I interferon expression during infection with the ICP0-null but not wild-type virus. In summary, by combining two proteomic approaches followed by confirmatory and functional experiments, we identified and validated multiple novel targets of ICP0 in neuronal cells, and revealed potential restrictive activities of SNX9 and OTUD4 as well as ICP0-dependent antagonism of these activities. Author SummaryHerpes simplex virus 1 (HSV-1) establishes latent infection in neurons. ICP0 is known for its critical role in antagonizing cellular restrictive functions thereby initiating productive infection. It has been demonstrated to be important for both acute infection and reactivation from latency in neurons. However, little is known about its targets in neuronal cells. Here we combined two proteomic approaches, interactome and ubiquitinome analyses, to integratively identify interaction partners and substrates of ICP0 in HSV-1 infected neuronal cells. The results identified many novel targets as well as confirming previously reported ones. We also further validated some of the binding interactions and ubiquitin modifications. Functional studies revealed that the ICP0-interacting protein SNX9 restricted HSV-1 replication and the ICP0 substrate OTUD4 was induced to enhance type I interferon expression during HSV-1 neuronal infection. Moreover, the activities of these proteins appeared to be antagonized by ICP0-dependent mechanisms. This study provided comprehensive insight into ICP0 targets in neuronal cells and might prompt further investigation into the newly identified targets of ICP0.

microbiology↗

bioRxiv2021

Structural and functional characterization of ubiquitin variant inhibitors for the JAMM-family deubiquitinases STAMBP and STAMBPL1

Ubiquitination is one of the most crucial post-translational protein modifications involved in a myriad of biological pathways. This process is reversed by deubiquitinases (DUBs) that deconjugate the ubiquitin (Ub) moiety or poly-Ub chains from substrates. In the past decade, tremendous efforts have been focused on targeting DUBs for drug discovery. However, most chemical compounds with inhibitory activity for DUBs suffer from mild potency and low selectivity. To overcome these obstacles, we developed a phage display-based protein engineering strategy for generating Ub variant (UbV) inhibitors and have previously successfully applied it to the Ub-specific protease (USP) family of cysteine proteases. In this work, we leveraged the UbV platform to target STAMBP, a member of the JAB1/MPN/MOV34 (JAMM) metalloprotease family of DUB enzymes. We identified two UbVs (UbVSP.1 and UbVSP.3) that bind to STAMBP with high affinity but differ in their selectivity for the closely related paralog STAMBPL1. We determined the STAMBPL1-UbVSP.1 complex structure by X-ray crystallography, revealing hotspots of the tight JAMM-UbV interaction. Finally, we show that UbVSP.1 and UbVSP.3 are potent inhibitors of the STAMBP isopeptidase activity, far exceeding the reported small-molecule inhibitor BC-1471. This work demonstrates that UbV technology is suitable to develop tool molecules for metalloproteases. These tools can be used to understand the cellular function of JAMM family DUBs.

biochemistry↗

bioRxiv2020

Are pangolins the intermediate host of the 2019 novel coronavirus (2019-nCoV) ?

The outbreak of 2019-nCoV pneumonia (COVID-19) in the city of Wuhan, China has resulted in more than 70,000 laboratory confirmed cases, and recent studies showed that 2019-nCoV (SARS-CoV-2) could be of bat origin but involve other potential intermediate hosts. In this study, we assembled the genomes of coronaviruses identified in sick pangolins. The molecular and phylogenetic analyses showed that pangolin Coronaviruses (pangolin-CoV) are genetically related to both the 2019-nCoV and bat Coronaviruses but do not support the 2019-nCoV arose directly from the pangolin-CoV. Our study also suggested that pangolin be natural host of Betacoronavirus, with a potential to infect humans. Large surveillance of coronaviruses in pangolins could improve our understanding of the spectrum of coronaviruses in pangolins. Conservation of wildlife and limits of the exposures of humans to wildlife will be important to minimize the spillover risks of coronaviruses from wild animals to humans.

pathology↗

bioRxiv2019

Effect of antenatal tetramethylpyrazine on lung development and YAP expression in a rat model of experimental congenital diaphragmatic hernia

Tetramethylpyrazine (TMP) is a chemical compound found in extracts derived from the Chinese medicinal plant. Due to its remarkable therapeutic effects, availability, and low cost and toxicity, TMP has been used to treat cardiovascular diseases and pulmonary hypertension in China. The aim of this study was to investigate the therapeutic effects and underlying mechanism of TMP on lung development using a rat model of nitrofen-induced congenital diaphragmatic hernia (CDH). Pregnant rats were divided into three groups: control, CDH, and CDH+TMP. Nitrofen was used to induce CDH. In the CDH and CDH+TMP, Fetuses only with left diaphragmatic hernias were chosen for analysis. Lung and body weight were recorded and lung histologic evaluations, image analysis, and western blot analysis of YAP, p-YAP and LATS1 were performed after lung processing. A marked abnormal structure was observed, as evidenced by pulmonary hypoplasia and vascular remodeling, in the CDH. These abnormalities were improved in the CDH+TMP. There were significant differences between the CDH and CDH+TMP in percentage of medial wall thickness, arteriole muscularization, radial alveolar counts, AA%, and alveolar septal thickness. YAP expression was markedly increased in the CDH compared to the control, which was not affected by antenatal TMP administration. However, prenatal TMP intervention significantly increased expression of LATS1 and phosphorylation of YAP in the CDH fetuses. Our results demonstrate that antenatal TMP administration improved vascular remodeling and promoted lung development in a rat model of CDH, potentially through increasing expression of LATS1 and phosphorylation of YAP.

developmental biology↗

bioRxiv2018

Garcinia cambogia extract removes calcium oxalate kidney stones in both genetic and non-genetic Drosophila models of nephrolithiasis

Kidney stone formers with family history have a high rate of stone recurrence after kidney stone removal surgery and there is no effective medication available for treatment. Here, we show that Garcinia cambogia extract (GCE) efficiently removes calcium oxalate kidney stones from Malpighian tubules in both genetic and non-genetic Drosophila models of nephrolithiasis, and hydroxycitrate -a major component of GCE, directly dissolves calcium oxalate stones in Drosophila Malpighian tubules ex vivo. Our study discovers a potential novel therapeutic strategy for the clinical treatment of nephrolithiasis and suggests that clinical-grade Garcinia cambogia extract could be used to treat patients with nephrolithiasis in the future.

pharmacology and toxicology↗

bioRxiv2018

Non-canonical role of E3 ligase RIPLET in innate immunity as a co-receptor for RIG-I

Ubiquitin (Ub) and its E3 ligases play diverse biological roles, from proteasomal degradation to innate immune signaling. The conventional view posits that E3 ligases function primarily through conjugating Ub to their substrate molecules. We report here that RIPLET, an essential E3 ligase in antiviral immunity, promotes the antiviral signaling activity of the viral RNA receptor RIG-I through both Ub-dependent and -independent manners. RIPLET utilizes its dimeric structure and the bivalent binding mode to preferentially recognize RIG-I preoligomerized on dsRNA. RIPLET can also adopt an alternative binding mode for filamentous oligomers of RIG-I assembled on longer dsRNAs, cross-bridging RIG-I filaments in both ubiquitin-dependent and-independent manners. The resultant receptor clustering leads to the formation of aggregate-like cytosolic granules and the stimulation of RIG-I-mediated antiviral signaling in a RNA-length dependent manner. These observations show the unexpected role of an E3 ligase as a co-receptor that directly participates in receptor oligomerization and ligand discrimination. This study also highlights previously unrecognized mechanisms by which an E3 ligase induces receptor clustering and signal amplification, and offers insights into the unique cellular function of membrane-less granule assembly.\n\nOne-sentence summaryRIPLET functions as a molecular glue to assemble signaling scaffolds for the antiviral innate immune receptor RIG-I.

immunology↗