Integrated-gut-liver-on-a-chip platform as an in vitro human model of non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) afflicts a significant percentage of the population; however, no effective treatments have yet been established because of the unsuitability of in vitro assays and animal experimental models. Here, we present an integrated-gut-liver-on-a-chip (iGLC) platform as an in vitro human model of the gut-liver axis (GLA) by co-culturing human gut and liver cell lines interconnected via microfluidics in a closed circulation loop, for the initiation and progression of NAFLD by treatment with free fatty acids (FFAs) for 1 and 7 days, respectively. Co-cultured Caco-2 gut-mimicking cells and HepG2 hepatocyte-like cells demonstrate the protective effects from apoptosis against FFAs treatment, whereas mono-cultured cells exhibit induced apoptosis. Phenotype and gene expression analyses reveal that the FFAs-treated gut and liver cells accumulated intracellular lipid droplets and show an increase in gene expression associated with a cellular response to copper ions and endoplasmic reticulum stress. As an in vitro human GLA model, the iGLC platform may serve as an alternative to animal experiments for investigating the mechanisms of NAFLD.

Ion Transport and Electrochemical Reaction in LiNi0.5Co0.2Mn0.3O2-Based High Energy/Power Lithium-Ion Batteries.

The high energy/power lithium-ion battery using LiNi0.5Co0.2Mn0.3O2 (NCM523 HEP LIB) has an excellent trade-off between specific capacity, cost, and stable thermal characteristics. However, it still brings a massive challenge for power improvement under low temperatures. Deeply understanding the electrode interface reaction mechanism is crucial to solving this problem. This work studies the impedance spectrum characteristics of commercial symmetric batteries under different states of charge (SOCs) and temperatures. The changing tendencies of the Li+ diffusion resistance Rion and charge transfer resistance Rct with temperature and SOC are explored. Moreover, one quantitative parameter, § ≡ Rct/Rion, is introduced to identify the boundary conditions of the rate control step inside the porous electrode. This work points out the direction to design and improve performance for commercial HEP LIB with common temperature and charging range of users.

Odorant Receptor OR2C1 Is an Essential Modulator of Boar Sperm Capacitation by Binding with Heparin.

Heparin, a class of glycosaminoglycans (GAGs), is widely used to induce sperm capacitation and fertilization. How heparin induces sperm capacitation remains unclear. Olfactory receptors (ORs) which are G protein-coupled receptors, have been proposed to be involved in sperm capacitation. However, the interaction between ORs and odor molecules and the molecular mechanism of ORs mediating sperm capacitation are still unclear. The present study aimed to explore the underlying interaction and mechanism between heparin and ORs in carrying out the boar sperm capacitation. The results showed that olfactory receptor 2C1 (OR2C1) is a compulsory unit which regulates the sperm capacitation by recognizing and binding with heparin, as determined by Dual-Glo Luciferase Assay and molecular docking. In addition, molecular dynamics (MD) simulation indicated that OR2C1 binds with heparin via a hydrophobic cavity comprises of Arg3, Ala6, Thr7, Asn171, Arg172, Arg173, and Pro287. Furthermore, we demonstrated that knocking down OR2C1 significantly inhibits sperm capacitation. In conclusion, we highlighted a novel olfactory receptor, OR2C1, in boar sperm and disclosed the potential binding of heparin to Pro287, a conserved residue in the transmembrane helices region 7 (TMH7). Our findings will benefit the further understanding of ORs involved in sperm capacitation and fertilization.

Oral Delivery of siRNA Using Fluorinated, Small-Sized Nanocapsules toward Anti-Inflammation Treatment.

Oral delivery of small interfering RNA (siRNA) provides a promising paradigm for treating diseases that require regular injections. However, the multiple gastrointestinal (GI) and systemic barriers often lead to inefficient oral absorption and low bioavailability of siRNA. Technologies that can overcome these barriers are still lacking, which hinders the clinical potential of orally delivered siRNA. Herein, small-sized, fluorinated nanocapsules (F-NCs) are developed to mediate efficient oral delivery of tumor necrosis factor α (TNF-α) siRNA for anti-inflammation treatment. The NCs possess a disulfide-cross-linked shell structure, thus featuring robust stability in the GI tract. Because of their small size (≈30 nm) and fluorocarbon-assisted repelling of mucin adsorption, the best-performing F3 -NCs show excellent mucus penetration and intestinal transport capabilities without impairing the intestinal tight junction, conferring the oral bioavailability of 20.4% in relative to intravenous injection. The disulfide cross-linker can be cleaved inside target cells, causing NCs dissociation and siRNA release to potentiate the TNF-α silencing efficiency. In murine models of acute and chronic inflammation, orally delivered F3 -NCs provoke efficient TNF-α silencing and pronounced anti-inflammatory efficacies. This study therefore provides a transformative strategy for oral siRNA delivery, and will render promising utilities for anti-inflammation treatment.

Complete Mitogenome of Oreolalax Omeimontis Reveals Phylogenetic Status and Novel Gene Arrangement of Archaeobatrachia.

Species of the genus Oreolalax displayed crucial morphological characteristics of vertebrates transitioning from aquatic to terrestrial habitats; thus, they can be regarded as a representative vertebrate genus for this landing phenomenon. But the present phylogenetic status of Oreolalax omeimontis has been controversial with morphological and molecular approaches, and specific gene rearrangements were discovered in all six published Oreolalax mitogenomes, which are rarely observed in Archaeobatrachia. Therefore, this study determined the complete mitogenome of O. omeimontis with the aim of identifying its precise phylogenetic position and novel gene arrangement in Archaeobatrachia. Phylogenetic analysis with Bayesian inference and maximum likelihood indicates O. omeimontis is a sister group to O. lichuanensis, which is consistent with previous phylogenetic analysis based on morphological characteristics, but contrasts with other studies using multiple gene fragments. Moreover, although the duplication of trnM occurred in all seven Oreolalax species, the translocation of trnQ and trnM occurred differently in O. omeimontis to the other six, and this unique rearrangement would happen after the speciation of O. omeimontis. In general, this study sheds new light on the phylogenetic relationships and gene rearrangements of Archaeobatrachia.

Low-Temperature Processed Brookite Interfacial Modification for Perovskite Solar Cells with Improved Performance.

The scaffold layer plays an important role in transporting electrons and preventing carrier recombination in mesoporous perovskite solar cells (PSCs), so the engineering of the interface between the scaffold layer and the light absorption layer has attracted widespread concern. In this work, vertically grown TiO2 nanorods (NRs) as scaffold layers are fabricated and further treated with TiCl4 aqueous solution. It can be found that a thin brookite TiO2 nanoparticle (NP) layer is formed by the chemical bath deposition (CBD) method on the surface of every rutile NR with a low annealing temperature (150 °C), which is beneficial for the infiltration and growth of perovskite. The PSC based on the TiO2 NR/brookite NP structure shows the best power conversion of 15.2%, which is 56.37% higher than that of the PSC based on bare NRs (9.72%). This complex structure presents an improved pore filling fraction and better carrier transport capability with less trap-assisted carrier recombination. In addition, low-annealing-temperature-formed brookite NPs possess a more suitable edge potential for electrons to transport from the perovskite layer to the electron collection layer when compared with high-annealing-temperature-formed anatase NPs. The brookite phase TiO2 fabricated at a low temperature presents great potential for flexible PSCs.

Complete Mitogenomes of Polypedates Tree Frogs Unveil Gene Rearrangement and Concerted Evolution within Rhacophoridae.

New developments in sequencing technology and nucleotide analysis have allowed us to make great advances in reconstructing anuran phylogeny. As a clade of representative amphibians that have radiated from aquatic to arboreal habitats, our understanding of the systematic status and molecular biology of rhacophorid tree frogs is still limited. We determined two new mitogenomes for the genus Polypedates (Rhacophoridae): P. impresus and P. mutus. We conducted comparative and phylogenetic analyses using our data and seven other rhacophorid mitogenomes. The mitogenomes of the genera Polypedates, Buergeria, and Zhangixalus were almost identical, except that the ATP8 gene in Polypedates had become a non-coding region; Buergeria maintained the legacy "LTPF" tRNA gene cluster compared to the novel "TLPF" order in the other two genera; and B. buergeri and Z. dennysi had no control region (CR) duplication. The resulting phylogenetic relationship supporting the above gene rearrangement pathway suggested parallel evolution of ATP8 gene loss of function (LoF) in Polypedates and CR duplication with concerted evolution of paralogous CRs in rhacophorids. Finally, conflicting topologies in the phylograms of 185 species reflected the advantages of phylogenetic analyses using multiple loci.

Gut-liver-axis microphysiological system for studying cellular fluidic shear stress and inter-tissue interaction.

To clarify the physiological and pathological roles of gut-liver-axis (GLA) in the human body, a GLA microphysiological system (GLA-MPS) holds great potential. However, in current GLA-MPSs, the importance of a physiologically relevant flow for gut and liver cells' cultivation is not fully addressed. In addition, the integration of individual organ perfusion, circulation flow, and organ tissue functions in a single device has not been achieved. Here, we introduce a GLA-MPS by integrating two cell-culture chambers with individually applied perfusion flows and a circulation channel with an on-chip pneumatic micropump under cell-culture chambers via a porous membrane for interconnecting them. We analyzed the fluid shear stress (FSS) with computational fluid dynamics simulations and confirmed that the physiologically relevant FSS could be applied to the gut (Caco-2) (8 × 10-3 dyn cm-2) and liver (HepG2) cells (1.2 × 10-7 dyn cm-2). Under the physiologically relevant flow, the Caco-2 and HepG2 cells in the GLA-MPS maintained a cell survival rate of 95% and 92%, respectively. Furthermore, the expression of functional proteins such as zonula occludens 1 (in Caco-2) and albumin (in HepG2) was enhanced. To demonstrate the GLA interaction, the inflammatory bowel disease was recapitulated by applying lipopolysaccharide for only Caco-2 cells. The inflammatory proteins, such as inducible nitric oxide synthase, were induced in Caco-2 and HepG2 cells. The presented GLA-MPS can be adapted as an advanced in vitro model in various applications for disease modeling associated with inter-tissue interactions, such as inflammatory disease.

Seasonal Prevalence of Gastrointestinal Parasites in Macaques (Macaca thibetana) at Mount Emei Scenic Area in China.

The aim of the study was to elucidate the prevalence of intestinal parasites in macaques at the Mt. Emei Scenic Area of Sichuan, China. A total of 168 fecal samples were collected from yellow (n = 31), black (n = 19), new (n = 57), Leidongping (n = 57) and Wuxiangang (n = 4) macaques from 2019 to 2020. The fecal samples were tested for various gastrointestinal parasites following the microscopic detection method. The results showed that the total prevalence rate of the intestinal parasite was 51.19% (86/168), whereas the intestinal parasite with the highest prevalence was Gongylonema spp. (26.79%) for helminth and Entamoeba spp. (18.45%) for protozoa. Interestingly, the highest prevalence of intestinal parasites was observed during the summer season (86.21%), and the lowest was observed during the winter season (7.14%). There was a positive correlation observed between the human contact frequency and total prevalence rate of the intestinal parasites (p < 0.05); however, there was no correlation between the human contact frequency and total prevalence of the intestinal parasites at different seasons (p > 0.05). In conclusion, the dominant parasites Gongylonema spp. and Entamoeba spp. cause various diseases that may be transmitted to humans and other animals; therefore, there is a need for a proper management system, such as parasite control measures and population protection in the Mt. Emei Scenic Area of Sichuan, China.

RhB-encapsulated metal-organic cage as a dual-emission fluorescence sensor for detection of malachite green and glycine.

RhB@ZrT-1-OH composite was constructed by introduction of Rhodamine B (RhB) into the cages of zirconium-based metal-organic cage that had two fluorescence emission peaks at 466 and 612 nm upon excitation at 327 nm. The dual-emission fluorescence sensor exhibits ultra-high sensitive detection for malachite green (MG) and glycine (Gly) in phosphate buffer solution (pH = 6.86). RhB@ZrT-1-OH as a ratiometric fluorescence probe was applied to detect MG with a low LOD of 0.2879 µM and presented obvious fluorescence visual changes from orange to purple to blue under 254 nm UV-vis lamp. Moreover, RhB@ZrT-1-OH also can be utilized as a "turn-on" fluorescence sensor to recognize Gly with a low LOD of 0.3747 µM and exhibits fluorescence color changes from orange to pink to purple. Notably, the corresponding test papers for sensing MG and Gly were designed for recognize the concentration of MG and Gly. Furthermore, the dual-emission fluorescence sensor can be used to detect MG and Gly in fish and human serum with high sensitivity and reliable. The possible detecting mechanisms of RhB@ZrT-1-OH for sensing MG and Gly were detailedly explored.

A Highly Sensitive and Specific Detection Method for Mycobacterium tuberculosis Fluoroquinolone Resistance Mutations Utilizing the CRISPR-Cas13a System.

Objectives: CRISPR-Cas13a system-based nucleic acid detection methods are reported to have rapid and sensitive DNA detection. However, the screening strategy for crRNAs that enables CRISPR-Cas13a single-base resolution DNA detection of human pathogens remains unclear. Methods: A combined rational design and target mutation-anchoring CRISPR RNA (crRNA) screening strategy was proposed. Results: A set of crRNAs was found to enable the CRISPR-Cas13 system to dramatically distinguish fluroquinolone resistance mutations in clinically isolated Mycobacterium tuberculosis strains from the highly homologous wild type, with a signal ratio ranging from 8.29 to 38.22 in different mutation sites. For the evaluation of clinical performance using genomic DNA from clinically isolated M. tuberculosis, the specificity and sensitivity were 100 and 91.4%, respectively, compared with culture-based phenotypic assays. Conclusion: These results demonstrated that the CRISPR-Cas13a system has potential for use in single nucleotide polymorphism (SNP) detection after tuning crRNAs. We believe this crRNA screening strategy will be used extensively for early drug resistance monitoring and guidance for clinical treatment.

Hypoxia-induced NFATc3 deSUMOylation enhances pancreatic carcinoma progression.

The transcriptional regulator nuclear factor of activated T-cells, cytoplasmic 3 (NFATc3) is constitutively activated in several cancer types and plays important roles in cancer development and progression. Heavily phosphorylated NFATc3 resides in the cytoplasm of resting cells, and dephosphorylated NFATc3 translocates to the nucleus to activate expression of target genes in cells exposed to stimuli, for instance, hypoxia. Apart from phosphorylation, various post-translational modifications have been reported to regulate NFAT transcriptional activity. However, the mechanisms remain elusive. Here, we have demonstrated that NFATc3 is activated in human pancreatic ductal adenocarcinoma (PDAC) cells and that excessive activation of NFATc3 is correlated to advanced stages of PDAC and short survival time of PDAC patients. NFATc3 is deSUMOylated at K384 by SENP3 under hypoxia, which impairs the interaction between NFATc3 and phosphokinase GSK-3ß, subsequently decreases NFATc3 phosphorylation and increases its nuclear occupancy. Knockdown of SENP3 greatly decreased hypoxia-induced NFATc3 nuclear occupancy. Our results highlight that SENP3-mediated deSUMOylation acts as an essential modulator of NFATc3, which is instrumental in PDAC tumor progression under hypoxia.

ROS1 fusion lung adenosquamous carcinoma patient with short-term clinical benefit after crizotinib treatment: a case report.

ROS1 rearrangements are validated drivers in non-small cell lung cancer (NSCLC), and occur at an extremely low rate in rare pathological subtypes such as adenosquamous carcinoma (ASC). Crizotinib is known to be effective in patients with ROS1-rearranged NSCLC. However, the efficacy of crizotinib in patients with ROS1-rearranged lung ASC is unknown. Here, we report the case of a 43-year-old female never-smoker who presented with dry cough for 3 months. The patient was then diagnosed with stage IIIA poorly-differentiated lung ASC with ROS1 rearrangement (CD74-ROS1). Programmed death-ligand 1 (PD-L1) expression was high with 50% in tumor cells of her lung puncture biopsy sample. The patient received albumin-bound paclitaxel and camrelizumab as the first-line treatment and achieved a stable disease (SD) response with progression-free survival (PFS) of 2 months. Subsequently, the patient received crizotinib as the second-line treatment and achieved a partial response (PR) with PFS of 4 months. No gene mutation other than CD74-ROS1 (C6:R34) rearrangement was detected from the lung biopsy sample after crizotinib resistance using a panel covering 520 cancer-related genes. We speculate that crizotinib may have a short duration of efficacy against lung ASC. This is the first case report of response to crizotinib for a lung ASC patient with ROS1 fusion, and may help future targeted therapy investigations and prognostic evaluation for patients with rare pathological subtypes of NSCLC.

A transcriptome analysis for 24-hour continuous sampled uterus reveals circadian regulation of the key pathways involved in eggshell formation of chicken.

Circadian timing system controlled the rhythmic events, for example, ovulation and oviposition in chickens. However, how biological clock mediates eggshell formation remains obscure. Here, A 24-h mRNA transcriptome analysis was carried out in the uterus of 18 chickens with similar oviposition time points to identify the rhythmic genes and to reveal critical genes and biological pathways involved in the eggshell biomineralization. JTK_CYCLE analysis and real-time PCR revealed a total of 1,793 genes from the sequencing database with 23,513 genes (FPKM>1) were rhythmic genes regulating the rhythmic system and the expression of typical clock genes Per2, Cry1, Bmal1, Clock, Per3, and Rev-erbß were rhythmically expressed, which suggested that endogenous clock in uterus might control the eggshell mineralization. Time of peak expression of the rhythmic genes was analyzed based on their acrophase. The main phases clustered at the periods from Zeitgeber time 0 (ZT0) to ZT4 (6:00-10:00) and from ZT10 to ZT14 (16:00-20:00). The rhythmic genes were annotated to the following Gene Ontology terms rhythmic process, lyase, ATP binding, cell membrane component. KEGG pathway enrichment analysis revealed the top 15 rhythmic genes were involved in vital biological pathways, including syndecan (1, 2, 3)-mediated signaling, post-translational regulation of adheres junction stability and disassembly, FoxO family signaling, TGF-ß receptor and transport of small molecular pathways. 166 of total 1,235 genes (13.4%) were defined as rhythmic transfer factors (TFs) and they were investigated expression time distribution of cis-elements of circadian clock system D-box, E-box, B-site, and Y-Box within 24 h. Results indicated that rhythmic TFs at each phase are potential drivers of their circadian transcription activities. Compared with the control, the expression abundances of ion transport elements SCNN1G, CA2, SPP1, and ATP1B1 were significantly decreased after the interference of Bmal1 gene in synchronized uterine tubular gland cells. Clock genes changed their expression along with the eggshell formation, indicating that there is circadian clock in the uterus of chicken and it regulates the expression of eggshell formation genes.

The Dominating Role of Genetic Background in Shaping Gut Microbiota of Honeybee Queen Over Environmental Factors.

A balanced, diverse gut microbiota is vital for animal health. The microbial population is shaped by multiple factors including genetic background and environment, but other determinants remain controversial. Numerous studies suggest that the dominant factor is genetic background while others emphasize the environmental factors. Here, we bred asexual hybridization queens (AHQs) of honeybees through nutritional crossbreeding (laid in Apis mellifera colony but bred in Apis cerana colony), sequenced their gut microbiome, and compared it with normally bred sister queens to determine the primary factor shaping the gut microbiota. Our results showed that the dominant genera in the gut microbiota of AHQs were Brevundimonas, Bombella, and Lactobacillus, and its microbial community was more related to A. mellifera queens. The AHQs had a moderate number of different bacterial species and diversity, but total bacterial numbers were low. There were more significant taxa identified in the comparison between AHQ and A. cerana queen according to LEfSe analysis results. The only genetic-specific taxon we figured out was Brevundimonas. The growth of core bacterial abundance showed different characteristics among different queen groups in the first week after emerging. Collectively, this study suggested that the genetic background played a more dominant role than environmental factors in shaping the gut microbiota of honeybee queen and the microbiota of midgut was more sensitive than that of rectum to this impact.

Influence of extracellular nanovesicles derived from adipose-derived stem cells on nucleus pulposus cell from patients with intervertebral disc degeneration.

An increasing number of individuals are suffering from lower back and neck pain caused by intervertebral disc degeneration each year. Although the application of mesenchymal stem cells (MSCs) has provided desirable results in the treatment of intervertebral disc degeneration, there are multiple risks associated with the directed application of MSCs. An increasing number of studies have suggested that stem cells, through the release of extracellular nanovesicles, have vital functions in tissue regeneration and repair with low risk. The present study investigated the effect of extracellular nanovesicles derived from adipose-derived stem cells (ADSCs) on nucleus pulposus (NP) cells from patients with intervertebral disc degeneration. Human NP cells were obtained from patients with intervertebral disc degeneration undergoing surgical procedures in addition to ADSCs from liposuction patients. ADSC-derived extracellular nanovesicles were isolated and characterized. The differentiation and biological activity of NP cells cultured with or without ADSC-derived extracellular nanovesicles were assessed and inflammatory factors and intervertebral disc degeneration-associated markers were also measured. The results indicated that extracellular nanovesicles derived from ADSCs increased the migration and proliferation of NP cells and inhibited inflammatory activity, suggesting their utility for the treatment of intervertebral disc degeneration.

De Novo Genome Assembly of Chinese Plateau Honeybee Unravels Intraspecies Genetic Diversity in the Eastern Honeybee, Apis cerana.

Apis cerana abansis, widely distributed in the southeastern margin of the Qinghai-Tibet Plateau, is considered an excellent model to study the phenotype and genetic variation for highland adaptation of Asian honeybee. Herein, we assembled and annotated the chromosome-scale assembly genome of A. cerana abansis with the help of PacBio, Illumina and Hi-C sequencing technologies in order to identify the genome differences between the A. cerana abansis and the published genomes of different A. cerana strains. The sequencing methods, assembly and annotation strategies of A. cerana abansis were more comprehensive than previously published A. cerana genomes. Then, the intraspecific genetic diversity of A. cerana was revealed at the genomic level. We re-identified the repeat content in the genome of A. cerana abansis, as well as the other three A. cerana strains. The chemosensory and immune-related proteins in different A. cerana strains were carefully re-identified, so that 132 odorant receptor subfamilies, 12 gustatory receptor subfamilies and 22 immune-related pathways were found. We also discovered that, compared with other published genomes, the A. ceranaabansis lost the largest number of chemoreceptors compared to other strains, and hypothesized that gene loss/gain might help different A. cerana strains to adapt to their respective environments. Our work contains more complete and precise assembly and annotation results for the A. cerana genome, thus providing a resource for subsequent in-depth related studies.

Transcriptome-wide m6A profiling reveals mRNA post-transcriptional modification of boar sperm during cryopreservation.

BACKGROUND: Cryopreservation induces transcriptomic and epigenetic modifications that strongly impairs sperm quality and function, and thus decrease reproductive performance. N6-methyladenosine (m6A) RNA methylation varies in response to stress and has been implicated in multiple important biological processes, including post-transcriptional fate of mRNA, metabolism, and apoptosis. This study aimed to explore whether cryopreservation induces m6A modification of mRNAs associated with sperm energy metabolism, cryoinjuries, and freezability. RESULTS: The mRNA and protein expression of m6A modification enzymes were significantly dysregulated in sperm after cryopreservation. Furthermore, m6A peaks were mainly enriched in coding regions and near stop codons with classical RRACH motifs. The mRNAs containing highly methylated m6A peaks (fts vs. fs) were significantly associated with metabolism and gene expression, while the genes with less methylated m6A peaks were primarily involved in processes regulating RNA metabolism and transcription. Furthermore, the joint analysis of DMMGs and differentially expressed genes indicated that both of these play a vital role in sperm energy metabolism and apoptosis. CONCLUSIONS: Our study is the first to reveal the dynamic m6A modification of mRNAs in boar sperm during cryopreservation. These epigenetic modifications may affect mRNA expression and are closely related to sperm motility, apoptosis, and metabolism, which will provide novel insights into understanding of the cryoinjuries or freezability of boar sperm during cryopreservation.

Protective effects of sodium butyrate on rotavirus inducing endoplasmic reticulum stress-mediated apoptosis via PERK-eIF2α signaling pathway in IPEC-J2 cells.

BACKGROUND: Rotavirus (RV) is a major pathogen that causes severe gastroenteritis in infants and young animals. Endoplasmic reticulum (ER) stress and subsequent apoptosis play pivotal role in virus infection. However, the protective mechanisms of intestinal damage caused by RV are poorly defined, especially the molecular pathways related to enterocytes apoptosis. Thus, the aim of this study was to investigate the protective effect and mechanism of sodium butyrate (SB) on RV-induced apoptosis of IPEC-J2 cells. RESULTS: The RV infection led to significant cell apoptosis, increased the expression levels of ER stress (ERS) markers, phosphorylated protein kinase-like ER kinase (PERK), eukaryotic initiation factor 2 alpha (eIF2α), caspase9, and caspase3. Blocking PERK pathway using specific inhibitor GSK subsequently reversed RV-induced cell apoptosis. The SB treatment significantly inhibited RV-induced ERS by decreasing the expression of glucose regulated protein 78 (GRP78), PERK, and eIF2α. In addition, SB treatment restrained the ERS-mediated apoptotic pathway, as indicated by downregulation of C/EBP homologous protein (CHOP) mRNA level, as well as decreased cleaved caspase9 and caspase3 protein levels. Furthermore, siRNA-induced GPR109a knockdown significantly suppressed the protective effect of SB on RV-induced cell apoptosis. CONCLUSIONS: These results indicate that SB exerts protective effects against RV-induced cell apoptosis through inhibiting ERS mediated apoptosis by regulating PERK-eIF2α signaling pathway via GPR109a, which provide new ideas for the prevention and control of RV.