Hydrogel Crosslinked with Nanoparticles for Prevention of Surgical Hemorrhage and Recurrence of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is acknowledged as an immunosuppressive neoplasm, whereby the inactive microenvironment facilitates immune tolerance and evasion of HCC. Post-surgical resected liver cancer exhibits a proclivity for relapse, rendering prevention of recurrence challenging as it may transpire at any point subsequent to surgery. Among the various anti-recurrence interventions, the primary clinical approach involving the administration of regimens atezolizumab and bevacizumab (A+T) is deemed the most efficacious in reversing the tumor microenvironment, albeit still lacking in complete satisfaction. Therefore, the objective is to utilize a recently developed block copolymer as a protective carrier for two specific monoclonal antibody drugs. Subsequently, a modified hemostatic hydrogel will be synthesized for application during hepatic surgery. The immunotherapy impact of this approach is significantly prolonged and intensified due to the combined hemostasis properties and controlled release of the constituents within the synthesized nanocomposite hydrogel. Furthermore, these nanocomposite hydrogels exhibit remarkable efficacy in preventing postoperative wound bleeding and substantially enhancing the safety of liver cancer resection. This research on the anti-recurrence hydrogel system presents a novel therapeutic approach for addressing local recurrence of liver cancer, potentially offering a substantial contribution to the field of surgical treatment for liver cancer in the future.

Taste Impairments in a Parkinson's Disease Model Featuring Intranasal Rotenone Administration in Mice.

BACKGROUND: Taste impairments are often accompanied by olfactory impairments in the early stage of Parkinson's disease (PD). The development of animal models is required to elucidate the mechanisms underlying taste impairments in PD. OBJECTIVE: This study was conducted to clarify whether the intranasal administration of rotenone causes taste impairments prior to motor deficits in mice. METHODS: Rotenone was administrated to the right nose of mice once a day for 1 or 4 week(s). In the 1-week group, taste, olfactory, and motor function was assessed before and after a 1-week recovery period following the rotenone administration. Motor function was also continuously examined in the 4-weeks group from 0 to 5 weeks. After a behavioral test, the number of catecholamine neurons (CA-Nos) was counted in the regions responsible for taste, olfactory, and motor function. RESULTS: taste and olfactory impairments were simultaneously observed without locomotor impairments in the 1-week group. The CA-Nos was significantly reduced in the olfactory bulb and nucleus of the solitary tract. In the 4-week group, locomotor impairments were observed from the third week, and a significant reduction in the CA-Nos was observed in the substantia nigra (SN) and ventral tegmental area (VTA) at the fifth week along with the weight loss. CONCLUSION: The intranasal administration of rotenone caused chemosensory and motor impairments in an administration time-period dependent manner. Since chemosensory impairments were expressed prior to the locomotor impairments followed by SN/VTA CA neurons loss, this rotenone administration model may contribute to the clarification of the prodromal symptoms of PD.

ASAP Score versus GALAD Score for detection of hepatitis C-related hepatocellular carcinoma: A multicenter case-control analysis.

Background: The GALAD and ASAP scores are two well-recognized algorithms to estimate the risk of hepatocellular carcinoma (HCC) based on gender, age, alpha-fetoprotein (AFP), protein induced by vitamin K absence or Antagonist-II (PIVKA-II) and AFP-L3 (included in the GALAD score but not in the ASAP score). The current study sought to compare the diagnostic performance of each score to detect HCC among patients infected with hepatitis C virus (HCV). Methods: A multicenter case-control study was undertaken in which blood samples were collected from HCVinfected patients with and without HCC. Using the area under the receiver operating characteristic curve (AUROC), ASAP and GALAD scores were compared relative to diagnostic performance to detect any stage HCV-HCC and early-stage HCV-HCC. Results: The analytic cohort included 168 HCV-HCC patients and a control group of 193 HCV-infected patients. The ASAP score had a higher AUROC to detect any stage HCV-HCC versus the GALAD score, both in the overall group (0.917 vs. 0.894, P=0.057) and in the cirrhosis subgroup (0.909 vs. 0.889, P=0.132). Similar results were noted relative to the detection of early-stage HCV-HCC, whether defined by BCLC staging (stage 0-A: 0.898 vs. 0.860, P=0.026) or 8th TNM staging (stage I: 0.899 vs. 0.870, P=0.070). In subgroup analysis to detect AFP-negative HCV-HCC, the ASAP score also demonstrated a higher AUROC than the GALAD score to detect any stage HCV-HCC in the AFP-negative subgroup (0.815 vs. 0.764, P=0.063). Conclusions: The ASAP score had better diagnostic performance for early detection of HCV-HCC compared with the GALAD score. The ASAP score may be preferrable to the GALAD score for HCC screening and surveillance among HCV-infected patients.

Genomic and EST microsatellites for Rhododendron aureum (Ericaceae) and cross-amplification in other congeneric species.

PREMISE OF THE STUDY: Our objective of this study was to develop genomic and expressed sequence tag (EST)-derived microsatellites for the endangered species Rhododendron aureum and access their transferability in R. dauricum and R. brachycarpum. • METHODS AND RESULTS: Twelve genomic microsatellites were isolated in R. aureum using the Fast Isolation by AFLP of Sequences Containing repeats (FIASCO) protocol and seven EST-derived microsatellites were characterized by screening the Rhododendron dbEST database of GenBank. The number of alleles per locus ranged from one to eight. The observed and expected heterozygosity varied from 0.00 to 1.00 and from 0.00 to 0.73, respectively. • CONCLUSIONS: A total of 19 microsatellite loci were developed for R. aureum. Sixteen and 10 of these loci were successfully amplified in R. brachycarpum and R. dauricum, respectively. These microsatellite markers will have potential applications in genetic diversity and conservation genetics studies.

Population genetic structures of two ecologically distinct species Betula platyphylla and B. ermanii inferred based on nuclear and chloroplast DNA markers.

Climatic oscillations during the last glacial maximum (LGM) significantly affected the distribution patterns and genetic structure of extant plants. Northeast China (NEC) is a major biodiversity center in East Asia, and the influence of historical climate change on NEC populations is critical for understanding species responses to future climate change. However, only a few phylogeographic studies of cool temperate deciduous tree species have been conducted in the area, and results are inconsistent for species with different niches or distribution areas. We employed multiple chloroplast and nuclear markers to investigate the genetic structure of two ecologically contrasting species, Betula platyphylla and B. ermanii, in NEC. Rare haplotypes were identified in the chloroplast genome of these species, and both exhibited high levels of nucleotide diversity based on a fragment of the nuclear gene G3PDH and microsatellites. Moreover, significant phylogeographic structure was detected for B. platyphylla, suggesting that these populations had recolonized from independent glacial refuges, whereas no genetic structure was found for B. ermanii. OPEN RESEARCH BADGES: The nSSR datasets used in the current study and the table of pairwise FST (below diagonal) and its standardized F'ST (above diagonal) among 25 populations based on seven SSRs are available from the Dryad (DOI: https://doi.org/10.5061/dryad.230d176). Sequences generated from this study were deposited in GenBank under Accession nos. KY199568-KY200162 and MK819541-MK819970.

Electrophysiological and Morphological Properties of α and γ Motoneurons in the Rat Trigeminal Motor Nucleus.

The muscle contraction during voluntary movement is regulated by activities of α- and γ-motoneurons (αMNs and γMNs, respectively). The tension of jaw-closing muscles can be finely tuned over a wide range. This excellent function is likely to be achieved by the specific populations of αMNs innervating jaw-closing muscles. Indeed, we have recently demonstrated that in the rat dorsolateral trigeminal motor nucleus (dl-TMN), the size distribution of αMNs was bimodal and the population of smaller αMNs showed a size distribution similar to that of γMNs, by immunohistochemically identifying αMNs and γMNs based on the expressions of estrogen-related receptor gamma (Err3) and neuronal DNA binding protein NeuN together with ChAT. This finding suggests the presence of αMNs as small as γMNs. However, differences in the electrophysiological membrane properties between αMNs and γMNs remain unknown also in the dl-TMN. Therefore, in the present study, we studied the electrophysiological membrane properties of MNs in the dl-TMN of infant rats at postnatal days 7-12 together with their morphological properties using whole-cell current-clamp recordings followed by immunohistochemical staining with an anti-NeuN and anti-ChAT antibodies. We found that the ChAT-positive and NeuN-positive αMNs were divided into two subclasses: the first one had a larger cell body and displayed a 4-aminopyridine (4-AP)-sensitive current while the second one had a smaller cell body and displayed a less prominent 4-AP-sensitive current and a low-threshold spike, suitable for their orderly recruitment. We finally found that γMNs showing ChAT-positive and NeuN-negative immunoreactivities had smaller cell bodies and displayed an afterdepolarization mediated by flufenamate-sensitive cation current. It is suggested that these electrophysiological and morphological features of MNs in the dl-TMN are well correlated with the precise control of occlusion.

Nicotinic activity depresses synaptic potentiation in layer V pyramidal neurons of mouse insular cortex.

The insular cortex is a critical brain region involved in nicotine addiction. However, its specific cellular and synaptic mechanisms underlying nicotine addiction remains largely unknown. In the present study, we examined how nicotine modulates synaptic transmission and plasticity in layer V pyramidal neurons of the mouse insular cortex. We also examined which type of neurons express functional nicotinic acetylcholine receptors (nAChRs) in layer V of the insular cortex. We found that nicotine suppresses synaptic potentiation induced by combination of presynaptic stimulation with postsynaptic depolarization (paired training). An application of nicotine significantly enhanced both spontaneous excitatory postsynaptic currents (EPSCs) and inhibitory postsynaptic currents (IPSCs): the former effect was mediated by activation of ß2-containing nAChRs while the latter one was mediated largely by activation of ß2-containing nAChRs and to a minor extent by activation of α7-containing nAChRs. The application of nicotine significantly enhanced evoked IPSCs but had no effect on evoked EPSCs. We also found that in layer V of the mouse insular cortex, majority of non-fast-spiking (non-FS) interneurons have ß2-containing nAChRs while about half of pyramidal neurons and FS interneurons have functional nAChRs. Blockade of GABAA receptors or ß2-containing nAChRs prevented the effects of nicotine on synaptic potentiation. Taken together, these results suggest that in layer V pyramidal neurons of the insular cortex, activation of ß2-containing nAChRs expressed in non-FS interneurons suppresses synaptic potentiation through enhancing GABAergic synaptic transmission. These findings provide important insights into the cellular and synaptic mechanisms of insular cortical changes in nicotine addiction.

A distinct functional distribution of α and γ motoneurons in the rat trigeminal motor nucleus.

Gamma-motoneurons (γMNs) play a crucial role in regulating isometric muscle contraction. The slow jaw-closing during mastication is one of the most functional isometric contractions, which is developed by the rank-order recruitment of alpha-motoneurons (αMNs) in a manner that reflects the size distribution of αMNs. In a mouse spinal motor nucleus, there are two populations of small and large MNs; the former was identified as a population of γMNs based on the positive expression of the transcription factor estrogen-related receptor 3 (Err3) and negative expression of the neuronal DNA-binding protein NeuN, and the latter as that of αMNs based on the opposite pattern of immunoreactivity. However, the differential identification of αMNs and γMNs in the trigeminal motor nucleus (TMN) remains an assumption based on the size of cell bodies that were retrogradely stained with HRP. We here examined the size distributions of αMNs and γMNs in the dorsolateral TMN (dl-TMN) by performing immunohistochemistry using anti-Err3 and anti-NeuN antibodies. The dl-TMN was identified by immunopositivity for vesicular glutamate transporter-1. Immunostaining for choline acetyltransferase and Err3/NeuN revealed that the dl-TMN is composed of 65% αMNs and 35% γMNs. The size distribution of αMNs was bimodal, while that of γMNs was almost the same as that of the population of small αMNs, suggesting the presence of αMNs as small as γMNs. Consistent with the size concept of motor units, the presence of smaller jaw-closing αMNs was coherent with the inclusion of jaw-closing muscle fibers with smaller diameters compared to limb muscle fibers.

A role of CB1R in inducing θ-rhythm coordination between the gustatory and gastrointestinal insula.

Anandamide (AEA) and N-oleoylethanolamine (OEA) are produced in the intestine and brain during fasting and satiety, respectively. Subsequently, AEA facilitates food intake via activation of cannabinoid type-1 receptors (CB1Rs) while OEA decreases food intake via activation of peroxisome proliferator-activated receptor-α (PPARα) and/or G-protein-coupled receptor 119 (GPR119). Neuronal activity in the gastrointestinal region of the autonomic insula (GI-Au-I) that rostrally adjoins the gustatory insula (Gu-I) increases during fasting, enhancing appetite while umami and sweet taste sensations in Gu-I enhances appetite in GI-Au-I, strongly suggesting the presence of a neural interaction between the Gu-I and GI-Au-I which changes depending on the concentrations of AEA and OEA. However, this possibility has never been investigated. In rat slice preparations, we demonstrate with voltage-sensitive dye imaging that activation of CB1Rs by AEA induces θ-rhythm oscillatory synchronization in the Gu-I which propagates into the GI-Au-I but stops at its caudal end, displaying an oscillatory coordination. The AEA-induced oscillation was abolished by a CB1R antagonist or OEA through activation of GPR119. Our results demonstrate that the neural coordination between the Gu-I and GI-Au-I is generated or suppressed by the opposing activities between CB1R and GPR119. This mechanism may be involved in the feeding behavior based on taste recognition.