The Effects of Microbial Additive Supplementation on Growth Performance, Blood Metabolites, Fecal Microflora, and Carcass Characteristics of Growing-Finishing Pigs.

This study aimed to assess the effects of microbial additives that produce antimicrobial and digestive enzymes on the growth performance, blood metabolites, fecal microflora, and carcass characteristics of growing-finishing pigs. A total of 180 growing-finishing pigs (Landrace × Yorkshire × Duroc; mixed sex; 14 weeks of age; 58.0 ± 1.00 kg) were then assigned to one of three groups with three repetitions (20 pigs) per treatment for 60 days of adaptation and 7 days of collection. Dietary treatments included 0, 0.5, and 1.0% microbial additives in the basal diet. For growth performance, no significant differences in the initial and final weights were observed among the dietary microbial additive treatments, except for the average daily feed intake, average daily gain, and feed efficiency. In terms of blood metabolites and fecal microflora, immunoglobulin G (IgG), blood urea nitrogen, blood glucose, and fecal lactic acid bacteria count increased linearly, and fecal E. coli counts decreased linearly with increasing levels of microbial additives but not growth hormones and Salmonella. Carcass quality grade was improved by the microbial additive. In addition, carcass characteristics were not influenced by dietary microbial additives. In conclusion, dietary supplementation with 1.0% microbial additive improved average daily gain, feed efficiency, IgG content, and fecal microflora in growing-finishing pigs.

Post-traumatic Transient Neurological Dysfunction: A Proposal for Pathophysiology.

Unexplained neurological deterioration is occasionally observed in patients with traumatic brain injuries (TBIs). We aimed to describe the clinical features of post-traumatic transient neurological dysfunction and provide new insight into its pathophysiology. We retrospectively collected data from patients with focal neurological deterioration of unknown origin during hospitalization for acute TBI for 48 consecutive months. Brain imaging, including computed tomography, diffusion-weighted imaging and perfusion-weighted imaging, and electroencephalography were conducted during the episodes. Fourteen (2.0%) patients experienced unexplained focal neurological deterioration among 713 patients who were admitted for traumatic intracranial hemorrhage during the study period. Aphasia was the predominant symptom in all patients, and hemiparesis or hemianopia was accompanied in three patients. These symptoms developed within 14 days after trauma. Structural imaging did not show any significant interval change, and electroencephalography showed persistent arrhythmic slowing in the corresponding hemisphere in most patients. Perfusion imaging revealed increased cerebral blood flow in the symptomatic hemisphere. Surgical intervention and anti-seizure medications were ineffective in abolishing the symptoms. The symptoms disappeared spontaneously after 4 h to 1 month. Transient neurological dysfunction (TND) can occur during the acute phase of TBI. Although TND may last longer than a typical transient ischemic attack or seizure, it eventually resolves regardless of treatment. Based on our observation, we postulate that this is a manifestation of spreading depolarization occurring in the injured brain, which is analogous to migraine aura.

Comparative rhythmic transcriptome profiling of human and mouse striatal subregions.

The human striatum can be subdivided into the caudate, putamen, and nucleus accumbens (NAc). In mice, this roughly corresponds to the dorsal medial striatum (DMS), dorsal lateral striatum (DLS), and ventral striatum (NAc). Each of these structures have some overlapping and distinct functions related to motor control, cognitive processing, motivation, and reward. Previously, we used a "time-of-death" approach to identify diurnal rhythms in RNA transcripts in these three human striatal subregions. Here, we identify molecular rhythms across similar striatal subregions collected from C57BL/6J mice across 6 times of day and compare results to the human striatum. Pathway analysis indicates a large degree of overlap between species in rhythmic transcripts involved in processes like cellular stress, energy metabolism, and translation. Notably, a striking finding in humans is that small nucleolar RNAs (snoRNAs) and long non-coding RNAs (lncRNAs) are among the most highly rhythmic transcripts in the NAc and this is not conserved in mice, suggesting the rhythmicity of RNA processing in this region could be uniquely human. Furthermore, the peak timing of overlapping rhythmic genes is altered between species, but not consistently in one direction. Taken together, these studies reveal conserved as well as distinct transcriptome rhythms across the human and mouse striatum and are an important step in understanding the normal function of diurnal rhythms in humans and model organisms in these regions and how disruption could lead to pathology.

Anti-Inflammatory Activity of 1,6,7-Trihydroxy-2-(1,1-dimethyl-2-propenyl)-3-methoxyxanthone Isolated from Cudrania tricuspidata via NF-κB, MAPK, and HO-1 Signaling Pathways in Lipopolysaccharide-Stimulated RAW 264.7 and BV2 Cells.

Neuroinflammation activated by microglia affects inflammatory pain development. This study aimed to explore the anti-inflammatory properties and mechanisms of 1,6,7-trihydroxy-2-(1,1-dimethyl-2-propenyl)-3-methoxyxanthone (THMX) from Cudrania tricuspidata in microglia activation-mediated inflammatory pain. In RAW 264.7 and BV2 cells, THMX has been shown to reduce lipopolysaccharide (LPS)-induced inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and pro-inflammatory mediators and cytokines, including nitric oxide (NO), prostaglandin (PG) E2, interleukin (IL)-6, and tumor necrosis factor alpha (TNF-α). THMX also decreased LPS-induced phosphorylation of mitogen-activated protein kinase (MAPK) and the activation of p65 nuclear factor kappa B (NF-κB). Interestingly, THMX also activated heme oxygenase (HO)-1 expression. These findings suggest that THMX is a promising biologically active compound against inflammation through preventing MAPKs and NF-ĸB and activating HO-1 signaling pathways.

The high optical brightness of the BlueWalker 3 satellite.

Large constellations of bright artificial satellites in low Earth orbit pose significant challenges to ground-based astronomy1. Current orbiting constellation satellites have brightnesses between apparent magnitudes 4 and 6, whereas in the near-infrared Ks band, they can reach magnitude 2 (ref. 2). Satellite operators, astronomers and other users of the night sky are working on brightness mitigation strategies3,4. Radio emissions induce further potential risk to ground-based radio telescopes that also need to be evaluated. Here we report the outcome of an international optical observation campaign of a prototype constellation satellite, AST SpaceMobile's BlueWalker 3. BlueWalker 3 features a 64.3 m2 phased-array antenna as well as a launch vehicle adaptor (LVA)5. The peak brightness of the satellite reached an apparent magnitude of 0.4. This made the new satellite one of the brightest objects in the night sky. Additionally, the LVA reached an apparent V-band magnitude of 5.5, four times brighter than the current International Astronomical Union recommendation of magnitude 7 (refs. 3,6); it jettisoned on 10 November 2022 (Universal Time), and its orbital ephemeris was not publicly released until 4 days later. The expected build-out of constellations with hundreds of thousands of new bright objects1 will make active satellite tracking and avoidance strategies a necessity for ground-based telescopes.

Circadian rhythm disruptions associated with opioid use disorder in synaptic proteomes of human dorsolateral prefrontal cortex and nucleus accumbens.

Opioid craving and relapse vulnerability is associated with severe and persistent sleep and circadian rhythm disruptions. Understanding the neurobiological underpinnings of circadian rhythms and opioid use disorder (OUD) may prove valuable for developing new treatments for opioid addiction. Previous work indicated molecular rhythm disruptions in the human brain associated with OUD, highlighting synaptic alterations in the dorsolateral prefrontal cortex (DLPFC) and nucleus accumbens (NAc)-key brain regions involved in cognition and reward, and heavily implicated in the pathophysiology of OUD. To provide further insights into the synaptic alterations in OUD, we used mass-spectrometry based proteomics to deeply profile protein expression alterations in bulk tissue and synaptosome preparations from DLPFC and NAc of unaffected and OUD subjects. We identified 55 differentially expressed (DE) proteins in DLPFC homogenates, and 44 DE proteins in NAc homogenates, between unaffected and OUD subjects. In synaptosomes, we identified 161 and 56 DE proteins in DLPFC and NAc, respectively, of OUD subjects. By comparing homogenate and synaptosome protein expression, we identified proteins enriched specifically in synapses that were significantly altered in both DLPFC and NAc of OUD subjects. Across brain regions, synaptic protein alterations in OUD subjects were primarily identified in glutamate, GABA, and circadian rhythm signaling. Using time-of-death (TOD) analyses, where the TOD of each subject is used as a time-point across a 24-h cycle, we were able to map circadian-related changes associated with OUD in synaptic proteomes associated with vesicle-mediated transport and membrane trafficking in the NAc and platelet-derived growth factor receptor beta signaling in DLPFC. Collectively, our findings lend further support for molecular rhythm disruptions in synaptic signaling in the human brain as a key factor in opioid addiction.

South Korean Nurses' Experiences of Speaking up for Patient Safety and Incident Prevention.

Despite the importance of speaking up for patient safety, hesitancy to do so remains a major contributing factor to communication failure. This study aimed to investigate the experiences of South Korean nurses in speaking up to prevent patient safety incidents. Twelve nurses responsible for patient safety tasks or with experience in patient safety education were recruited from five hospitals (three university hospitals, two general hospitals) in city "B". Data were collected through open-ended questions and in-depth interviews, transcribed, and analyzed using the inductive content analysis method. The study resulted in the identification of four main categories and nine subcategories that captured commonalities among the experience of the 12 nurses. The four main categories were as follows: the current scenario of speaking up, barriers to speaking up, strategies for speaking, and confidence training. There is a scarcity of research on speaking-up experiences for patient safety among nurses in South Korean. Overall, it is necessary to overcome cultural barriers and establish an environment that encourages speaking up. In addition, developing speaking-up training programs for nursing students and novice nurses is imperative to prevent patient safety incidents.

Circadian rhythm disruptions associated with opioid use disorder in the synaptic proteomes of the human dorsolateral prefrontal cortex and nucleus accumbens.

Opioid craving and relapse vulnerability is associated with severe and persistent sleep and circadian rhythm disruptions. Understanding the neurobiological underpinnings of circadian rhythms and opioid use disorder (OUD) may prove valuable for developing new treatments for opioid addiction. Previous work indicated molecular rhythm disruptions in the human brain associated with OUD, highlighting synaptic alterations in the dorsolateral prefrontal cortex (DLPFC) and nucleus accumbens (NAc)-key brain regions involved in cognition and reward, and heavily implicated in the pathophysiology of OUD. To provide further insights into the synaptic alterations in OUD, we used mass-spectrometry based proteomics to deeply profile protein expression alterations in bulk tissue and synaptosome preparations from DLPFC and NAc of unaffected and OUD subjects. We identified 55 differentially expressed (DE) proteins in DLPFC homogenates, and 44 DE proteins in NAc homogenates, between unaffected and OUD subjects. In synaptosomes, we identified 161 and 56 DE proteins in DLPFC and NAc, respectively, of OUD subjects. By comparing homogenate and synaptosome protein expression, we identified proteins enriched specifically in synapses that were significantly altered in both DLPFC and NAc of OUD subjects. Across brain regions, synaptic protein alterations in OUD subjects were primarily identified in glutamate, GABA, and circadian rhythm signaling. Using time-of-death (TOD) analyses, where the TOD of each subject is used as a time-point across a 24- hour cycle, we were able to map circadian-related changes associated with OUD in synaptic proteomes related to vesicle-mediated transport and membrane trafficking in the NAc and platelet derived growth factor receptor beta signaling in DLPFC. Collectively, our findings lend further support for molecular rhythm disruptions in synaptic signaling in the human brain as a key factor in opioid addiction.

Highly Stretchable PPy/PDMS Strain Sensors Fabricated with Multi-Step Oxygen Plasma Treatment.

We present highly stretchable polypyrrole (PPy)/polydimethylsiloxane strain sensors of highly improved sensitivity and durability fabricated by a chemical oxidative polymerization with oxygen plasma treatment (O2 PT). In this study, O2 PT was performed for 30, 60, and 90 s at each growth stage of the PPy film in three steps to investigate the effects on the sensor performance as well as the microstructural properties of the PPy films. Bonding characteristics with underlying layers and resistance to microcrack generation of the multi-layer PPy films under our given strained state were significantly enhanced by the O2 PT. The best sensor performance in terms of sensitivity and stability were achieved by PT for 30 s with a maximum gauge factor of ~438 at a uniaxial strain of 50%, excellent durability over 500 stretching/release cycles, and a fast response time of ~50 ms.

Performance evaluation of an electrostatic precipitator with a copper plate using an aerosolized SARS-CoV-2 surrogate (bacteriophage phi 6).

The global spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has reminded us of the importance of developing technologies to reduce and control bioaerosols in built environments. For bioaerosol control, the interaction between researchers and biomaterials is essential, and considering the characteristics of target pathogens is strongly required. Herein, we used enveloped viral aerosols, bacteriophage phi 6, for evaluating the performance of an electrostatic precipitator (ESP) with a copper-collecting plate (Cu-plate). In particular, bacteriophage phi 6 is an accessible enveloped virus that can be operated in biosafety level (BSL)-1 as a promising surrogate for SARS-CoV-2 with structural and morphological similarities. ESP with Cu-plate showed >91% of particle removal efficiency for viral aerosols at 77 cm/s of airflow face velocity. Moreover, the Cu-plate presented a potent antiviral performance of 5.4-relative log reduction within <15 min of contact. We believe that the evaluation of ESP performance using an aerosolized enveloped virus and plaque assay is invaluable. Our results provide essential information for the development of bioaerosol control technologies that will lead the post-corona era.

Antifungal and carboxylesterase-producing bacteria applied into corn silage still affected the fermented total mixed ration.

OBJECTIVE: This study investigated the effects of corn silage as a source of microbial inoculant containing antifungal and carboxylesterase-producing bacteria on fermentation, aerobic stability, and nutrient digestibility of fermented total mixed ration (FTMR) with different energy levels. METHODS: Corn silage was used as a bacterial source by ensiling for 72 d with an inoculant mixture of Lactobacillus brevis 5M2 and L. buchneri 6M1 at a 1:1 ratio. The corn silage without or with inoculant (CON vs MIX) was mixed with the other ingredients to formulate for low and high energy diets (LOW vs HIGH) for Hanwoo steers. All diets were ensiled into 20 L mini silo (5 kg) for 40 d in quadruplicate. RESULTS: The MIX diets had lower (p<0.05) acid detergent fiber with higher (p<0.05) in vitro digestibilities of dry matter and neutral detergent fiber compared to the CON diets. In terms of fermentation characteristics, the MIX diets had higher (p<0.05) acetate than the CON diets. The MIX diets had extended (p<0.05) lactic acid bacteria growth at 4 to 7 d of aerobic exposure and showed lower (p<0.05) yeast growth at 7 d of aerobic exposure than the CON diets. In terms of rumen fermentation, the MIX diets had higher (p<0.05) total fermentable fraction and total volatile fatty acid, with lower (p<0.05) pH than those of CON diets. The interaction (p = 0.036) between inoculant and diet level was only found in the immediately fermentable fraction, which inoculant was only effective on LOW diets. CONCLUSION: Application of corn silage with inoculant on FTMR presented an antifungal effect by inhibiting yeast at aerobic exposure and a carboxylesterase effect by improving nutrient digestibility. It also indicated that fermented feedstuffs could be used as microbial source for FTMR. Generally, the interaction between inoculant and diet level had less effect on this FTMR study.

A taxonomic study on the genus Stichillus (Diptera: Phoridae) from South Korea, with a key to species from East Asia.

The South Korean species of the genus Stichillus Enderlein are reviewed and four species are newly recognized. One of them, S. koreanus sp. nov., is described as new to science and the other three species, viz. S. cylindratus Nakayama & Shima, S. japonicus (Matsumura) and S. spinosus Liu & Chou are new to South Korea. Detailed descriptions with photographs of four Korean Stichillus species, and a revised key to males of ten species from East Asia except Mongolia and North Korea are provided.

A taxonomic study on the South Korean Diplonevra (Diptera: Phoridae).

The South Korean species of the genus Diplonevra are revised and eight species are recognized. Three of these species, D. biflagella, sp. nov., D. incisura, sp. nov., and D. nigritarsis, sp. nov., are new to science and four species, D. abbreviata (von Roser, 1840), D. florescens (Turton, 1801), D. hirsuta Michailovskaya, 2000, and D. peregrina (Wiedemann, 1830), are described for the first time in Korea. Distribution of D. bifasciata (Walker, 1860), the only previously recorded species in Korean checklists, is confirmed based on figures of a female specimen in previous publications. Diplonevra lamella Liu Yang, 2016 is considered a junior synonym of D. hirsuta Michailovskaya, 2000. The Chinese and Russian Far East records of D. pachycera (nec Schmitz) are treated as misidentifications of D. incisura, sp. nov. and D. nigritarsis, sp. nov., respectively. Also, the Chinese record of D. taigaensis (nec Michailovskaya) should be identified as D. biflagella, sp. nov. Detailed descriptions and photographs of three new species and four redescribed species and keys to eight males and seven females of Diplonevra species in South Korea are provided.

Role of Seed Layer Crystalline Quality in Photoresponse Performance of Hydrothermally Grown ZnO Nanorods.

We investigated the effects of the crystalline state for seed layers (SLs) on the growth morphology and material characteristics for hydrothermally grown ZnO nanorods (NRs). For this, preheating (PH) at different temperatures (100-300 °C) and O2 plasma treatment (PT) for 9 min were performed during the growth of SLs on p-Si by the aqueous solution-based method to provide the characteristic change on the NR growth platform. An improvement in material properties was achieved from the ZnO NRs grown on the SL crystals of enhanced crystalline quality in terms of the increased preferred orientation (002), the higher UV emission with suppressed deep-level emissions, the recovery of O/Zn stoichiometry, and the reduction of various intrinsic defects. Ultraviolet photodiodes of a p-Si/n-ZnO-NR structure fabricated under the SL conditions of O2 PT and PH at 100 °C showed a significantly enhanced on-off current ratio of ~90 at +5 V and faster photoresponse characteristics presenting a reduction in the fall time from 16 to 9 s.

Properties of Cellulose Pulp and Polyurethane Composite Films Fabricated with Curcumin by Using NMMO Ionic Liquid.

Cellulose pulp (CP), polyurethane (PU), and curcumin-based biocompatible composite films were prepared using a simple cost-effective method. Significant structural and microstructural changes were studied using FT-IR spectroscopy, XRD, and SEM. The 5% and 10% gravimetric losses of the CP/PU/curcumin composite were found to be in the range 87.2-182.3 °C and 166.7-249.8 °C, respectively. All the composites exhibited single Tg values in the range 147.4-154.2 °C. The tensile strength of CP was measured to be 93.2 MPa, which dropped to 14.1 MPa for the 1:0.5 CP/PU composite and then steadily increased to 30.5 MPa with further addition of PU. The elongation at the break of the composites decreased from 8.1 to 3.7% with the addition of PU. The addition of PU also improved the water vapor permeability (3.96 × 10-9 to 1.75 × 10-9 g m-1 s-1 Pa-1) and swelling ratio (285 to 202%) of the CP composite films. The CP/PU/curcumin composite exhibited good antioxidant activity and no cytotoxicity when tested on the HaCat cell line. The visual appearance and UV transmittance (86.2-32.9% at 600 nm) of the CP composite films were significantly altered by the incorporation of PU and curcumin. This study demonstrates that CP/PU/curcumin composites can be used for various packaging and biomedical applications.

Molecular rhythm alterations in prefrontal cortex and nucleus accumbens associated with opioid use disorder.

Severe and persistent disruptions to sleep and circadian rhythms are common in people with opioid use disorder (OUD). Preclinical evidence suggests altered molecular rhythms in the brain modulate opioid reward and relapse. However, whether molecular rhythms are disrupted in the brains of people with OUD remained an open question, critical to understanding the role of circadian rhythms in opioid addiction. Using subjects' times of death as a marker of time of day, we investigated transcriptional rhythms in the brains of subjects with OUD compared to unaffected comparison subjects. We discovered rhythmic transcripts in both the dorsolateral prefrontal cortex (DLPFC) and nucleus accumbens (NAc), key brain areas involved in OUD, that were largely distinct between OUD and unaffected subjects. Fewer rhythmic transcripts were identified in DLPFC of subjects with OUD compared to unaffected subjects, whereas in the NAc, nearly double the number of rhythmic transcripts was identified in subjects with OUD. In NAc of subjects with OUD, rhythmic transcripts peaked either in the evening or near sunrise, and were associated with an opioid, dopamine, and GABAergic neurotransmission. Associations with altered neurotransmission in NAc were further supported by co-expression network analysis which identified OUD-specific modules enriched for transcripts involved in dopamine, GABA, and glutamatergic synaptic functions. Additionally, rhythmic transcripts in DLPFC and NAc of subjects with OUD were enriched for genomic loci associated with sleep-related GWAS traits, including sleep duration and insomnia. Collectively, our findings connect transcriptional rhythm changes in opioidergic, dopaminergic, GABAergic signaling in the human brain to sleep-related traits in opioid addiction.

Usefulness of Self-Expandable Stent for Recanalization of Intracranial Atherosclerotic Disease: Preliminary Experience with Enterprise Stent.

PURPOSE: The purpose of this preliminary study is to evaluate the efficacy and safety of the Enterprise stent for intracranial atherosclerotic disease (ICAD) in patients who presented with acute stroke due to vessel steno-occlusion and in patients with symptomatic disease despite optimum medical management. MATERIALS AND METHODS: A retrospective data analysis was performed on 15 consecutive patients who were treated with Enterprise stenting for recanalization of symptomatic intracranial steno-occlusive arteries due to underlying ICAD. Their clinical and radiological data were reviewed to evaluate procedural results, periprocedural and postprocedural complications, and clinical outcome. RESULTS: Enterprise stents were deployed as a rescue method in 15 patients for recanalization of steno-occlusion. All patients achieved final modified thrombolysis in cerebral infarction (mTICI) score improvement (53.3% with a mTICI score from 0 to 2b or 3, 46.7% with a mTICI score from 1 to 3). Two postprocedural complications (1 symptomatic intracranial hemorrhage and 1 severe brain edema, 13.3%) occurred among 15 patients. Among 12 patients with acute ischemic stroke (AIS), 6 patients (50%) had improvement in their National Institute of Health Stroke Scale of more than 4 at discharge. Seven patients (58.3%) had a good functional outcome with 3-month modified Rankin Score (mRS)≤2, and mortality occurred (mRS=6) in 2 patients (16.7%). None of the 10 AIS and 3 transient ischemic attack patients experienced further ischemic events attributable to the treated steno-occlusion during the follow-up period (ranged from 4 to 36 months, median 12 months). CONCLUSION: This retrospective study suggests that Enterprise stenting can effectively and safely achieve recanalization in symptomatic steno-occlusive intracranial arteries.

Macluraxanthone B inhibits LPS-induced inflammatory responses in RAW264.7 and BV2 cells by regulating the NF-κB and MAPK signaling pathways.

OBJECTIVE: The prenylated xanthones compounds, macluraxanthone B (MCXB) was isolated from the MeOH extracts of Cudrania tricuspidata. In this study, we investigated the effect of MCXB on inflammatory response. MATERIALS AND METHODS: Anti-inflammatory effects of MCXB were examined in lipopolysaccharide (LPS)-stimulated RAW264.7 and BV2 cells. We observed their anti-inflammatory effects by ELISA, western blot analysis, and immunofluorescence. RESULTS: MCXB significantly inhibited the LPS-stimulated production of nitric oxide (NO), prostaglandin E2 (PGE2), interleukin-6 (IL-6), and tumor necrosis factor (TNF)-α in RAW264.7 and BV2 cells. MCXB also reduced the LPS-induced expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 proteins. Incubating cells with MCXB prevented subsequent activation of the nuclear factor kappa B (NF-κB) signaling pathway by inhibiting the nuclear localization and DNA-binding activity of the p65 subunit induced by LPS. MCXB inhibited the phosphorylation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and p38 mitogen-activated protein kinases (MAPKs) in RAW264.7 and BV2 cells. MCXB induced the expression of heme oxygenase (HO)-1 protein, and the inhibitory effect of MCXB on nitric oxide production was partially reversed by a selective HO-1 inhibitor. DISCUSSION AND CONCLUSIONS: Our results suggested that the anti-inflammatory effect of MCXB is partly regulated by HO-1 induction. In conclusion, MCXB could be a useful candidate for the development of therapeutic and preventive agents to treat inflammatory diseases.

Characterization of the liver immune microenvironment in liver biopsies from patients with chronic HBV infection.

BACKGROUND & AIMS: We aim to describe the liver immune microenvironment by analyzing liver biopsies from patients with chronic HBV infection (CHB). Host immune cell signatures and their corresponding localization were characterized by analyzing the intrahepatic transcriptome in combination with a custom multiplex immunofluorescence panel. METHOD: Matching FFPE and fresh frozen liver biopsies were collected from immune active patients within the open-label phase IV study GS-US-174-0149. RNA-Seq was conducted on 53 CHB liver biopsies from 46 patients. Twenty-eight of the 53 samples had matched FFPE biopsies and were stained with a 12-plex panel including cell segmentation, immune and viral biomarkers. Corresponding serum samples were screened using the MSD Human V-plex Screen Service to identify peripheral correlates for the immune microenvironment. RESULTS: Using unsupervised clustering of the transcriptome, we reveal two unique liver immune signatures classified as immune high and immune low based on the quantification of the liver infiltrate gene signatures. Multiplex immunofluorescence analysis demonstrated large periportal lymphoid aggregates in immune high samples consisting of CD4 and CD8 T cells, B cells and macrophages. Differentiation of the high and low immune microenvironments was independent of HBeAg status and peripheral viral antigen levels. In addition, longitudinal analysis indicates that treatment and normalization of ALT correlates with a decrease in liver immune infiltrate and inflammation. Finally, we screened a panel of peripheral biomarkers and identified ICAM-1 and CXCL10 as biomarkers that strongly correlate with these unique immune microenvironments. CONCLUSION: These data provide a description of immune phenotypes in patients with CHB and show that immune responses are downregulated in the liver following nucleotide analogue treatment. This may have important implications for both the safety and efficacy of immune modulator programs aimed at HBV cure. LAY SUMMARY: Liver biopsies from patients with chronic hepatitis B were submitted to RNA-Seq and multiplex immunofluorescence and identified two different liver immune microenvironments: immune high and immune low. Immune high patients showed elevated immune pathways, including interferon signaling pathways, and increase presence of immune cells. Longitudinal analysis of biopsies from treatment experienced patients showed that treatment correlates with a marked decrease in inflammation and these findings may have important implications for both safety and efficacy of immune modulator programs for HBV cure.

Taxonomic study on Sinopoda Jäger, 1999 (Araneae, Sparassidae, Heteropodinae), with three new species from Korea.

The genus Sinopoda Jäger, 1999 is a group of huntsman spiders (Araneae: Sparassidae: Heteropodinae), and currently seven species have been reported in Korea. In this study, three new species are described from Korea, Sinopodabigibba sp. nov., Sinopodabogil sp. nov., and Sinopodapantherina sp. nov.; Sinopodajirisanensis Kim & Chae, 2013 is revalidated with neotype designation, and had been formerly synonymized with Sinopodaforcipata (Karsch, 1881). Additionally, all previous records of Sinopodastellatops Jäger & Ono, 2002 and S.forcipata from Korea are deemed misidentifications of S.jirisanensis and S.bogil sp. nov., respectively.