A Prelimbic Cortex-Thalamus Circuit Bidirectionally Regulates Innate and Stress-induced Anxiety-like Behavior.

Anxiety-related disorders respond to cognitive behavioral therapies, which involved the medial prefrontal cortex (mPFC). Previous studies have suggested that subregions of the mPFC have different and even opposite roles in regulating innate anxiety. However, the specific causal targets of their descending projections in modulating innate anxiety and stress-induced anxiety have yet to be fully elucidated. Here, we found that among the various downstream pathways of the prelimbic cortex (PL), a subregion of the mPFC, PL-mediodorsal thalamic nucleus (MD) projection and PL-ventral tegmental area (VTA) projection exhibited antagonistic effects on anxiety-like behavior, while the PL-MD projection but not PL-VTA projection was necessary for the animal to guide anxiety-related behavior. In addition, MD-projecting PL neurons bidirectionally regulated remote but not recent fear memory retrieval. Notably, restraint stress induced high-anxiety state accompanied by strengthening the excitatory inputs onto MD-projecting PL neurons, and inhibiting PL-MD pathway rescued the stress-induced anxiety. Our findings reveal that the activity of PL-MD pathway may be an essential factor to maintain certain level of anxiety, and stress increased the excitability of this pathway, leading to inappropriate emotional expression, and suggest that targeting specific PL circuits may aid the development of therapies for the treatment of stress-related disorders.Significance statement This study provides insight into PL downstream pathways for regulating innate and stress-induced anxiety-like behavior. We reported that PL-mediodorsal thalamic nucleus (MD) projection and PL-ventral tegmental area (VTA) projection exhibited antagonistic effects on anxiety-like behavior, while the PL-MD projection but not PL-VTA projection was necessary for the animal to guide anxiety-related behavior. In addition, this study provides definite evidence that MD-projecting PL neurons bidirectionally regulated remote fear memory retrieval and concordant with a role for the PL-MD in anxiety. Moreover, this study is the first demonstration that restraint stress induced high-anxiety state accompanied by strengthening the excitatory inputs onto MD-projecting PL neurons, and inhibiting PL-MD pathway rescued the stress-induced anxiety.

Mature astrocytes as source for astrocyte repopulation after deletion in the medial prefrontal cortex: Implications for depression.

The adult brain retains a high repopulation capacity of astrocytes after deletion, and both mature astrocytes in the neocortex and neural stem cells in neurogenic regions possess the potential to generate astrocytes. However, the origin and the repopulation dynamics of the repopulating astrocytes after deletion remain largely unclear. The number of astrocytes is reduced in the medial prefrontal cortex (mPFC) of patients with depression, and selective elimination of mPFC astrocytes is sufficient to induce depression-like behaviors in rodents. However, whether astrocyte repopulation capacity is impaired in depression is unknown. In this study, we used different transgenic mouse lines to genetically label different cell types and demonstrated that in the mPFC of normal adult mice of both sexes, mature astrocytes were a major source of the repopulating astrocytes after acute deletion induced by an astrocyte-specific toxin, L-alpha-aminoadipic acid (L-AAA), and astrocyte regeneration was accomplished within two weeks accompanied by reversal of depression-like behaviors. Furthermore, re-ablation of mPFC astrocytes post repopulation led to reappearance of depression-like behaviors. In adult male mice subjected to 14-day chronic restraint stress, a well-validated mouse model of depression, the number of mPFC astrocytes was reduced; however, the ability of mPFC astrocytes to repopulate after L-AAA-induced deletion was largely unaltered. Our study highlights a potentially beneficial role for repopulating astrocytes in depression and provides novel therapeutic insights into enhancing local mature astrocyte generation in depression.

Dopamine D2 receptors in pyramidal neurons in the medial prefrontal cortex regulate social behavior.

Drugs acting on dopamine D2 receptors are widely used for the treatment of several neuropsychiatric disorders, including schizophrenia and depression. Social deficits are a core symptom of these disorders. Pharmacological manipulation of dopamine D2 receptors (Drd2), a Gi-coupled subtype of dopamine receptors, in the medial prefrontal cortex (mPFC) has shown that Drd2 is implicated in social behaviors. However, the type of neurons expressing Drd2 in the mPFC and the underlying circuit mechanism regulating social behaviors remain largely unknown. Here, we show that Drd2 were mainly expressed in pyramidal neurons in the mPFC and that the activation of the Gi-pathway in Drd2+ pyramidal neurons impaired social behavior in male mice. In contrast, the knockdown of D2R in pyramidal neurons in the mPFC enhanced social approach behaviors in male mice and selectively facilitated the activation of mPFC neurons projecting to the nucleus accumbens (NAc) during social interaction. Remarkably, optogenetic activation of mPFC-to-NAc-projecting neurons mimicked the effects of conditional D2R knockdown on social behaviors. Altogether, these results demonstrate a cell type-specific role for Drd2 in the mPFC in regulating social behavior, which may be mediated by the mPFC-to-NAc pathway.

A Distinct Metabolically Defined Central Nucleus Circuit Bidirectionally Controls Anxiety-Related Behaviors.

Anxiety disorders are debilitating psychiatric diseases that affect ∼16% of the world's population. Although it has been proposed that the central nucleus of the amygdala (CeA) plays a role in anxiety, the molecular and circuit mechanisms through which CeA neurons modulate anxiety-related behaviors are largely uncharacterized. Soluble epoxide hydrolase (sEH) is a key enzyme in the metabolism of polyunsaturated fatty acids (PUFAs), and has been shown to play a role in psychiatric disorders. Here, we reported that sEH was enriched in neurons in the CeA and regulated anxiety-related behaviors in adult male mice. Deletion of sEH in CeA neurons but not astrocytes induced anxiety-like behaviors. Mechanistic studies indicated that sEH was required for maintaining the the excitability of sEH positive neurons (sEHCeA neurons) in the CeA. Using chemogenetic manipulations, we found that sEHCeA neurons bidirectionally regulated anxiety-related behaviors. Notably, we identified that sEHCeA neurons directly projected to the bed nucleus of the stria terminalis (BNST; sEHCeA-BNST). Optogenetic activation and inhibition of the sEHCeA-BNST pathway produced anxiolytic and anxiogenic effects, respectively. In summary, our studies reveal a set of molecular and circuit mechanisms of sEHCeA neurons underlying anxiety.SIGNIFICANCE STATEMENT Soluble epoxide hydrolase (sEH), a key enzyme that catalyzes the degradation of EETs, is shown to play a key role in mood disorders. It is well known that sEH is mostly localized in astrocytes in the prefrontal cortex and regulates depressive-like behaviors. Notably, sEH is also expressed in central nucleus of the amygdala (CeA) neurons. While the CeA has been studied for its role in the regulation of anxiety, the molecular and circuit mechanism is quite complex. In the present study, we explored a previously unknown cellular and circuitry mechanism that guides sEHCeA neurons response to anxiety. Our findings reveal a critical role of sEH in the CeA, sEHCeA neurons and CeA-bed nucleus of the stria terminalis (BNST) pathway in regulation of anxiety-related behaviors.

Distinct roles of astroglia and neurons in synaptic plasticity and memory.

Long-term potentiation (LTP) in the hippocampus is the most studied form of synaptic plasticity. Temporal integration of synaptic inputs is essential in synaptic plasticity and is assumed to be achieved through Ca2+ signaling in neurons and astroglia. However, whether these two cell types play different roles in LTP remain unknown. Here, we found that through the integration of synaptic inputs, astrocyte inositol triphosphate (IP3) receptor type 2 (IP3R2)-dependent Ca2+ signaling was critical for late-phase LTP (L-LTP) but not early-phase LTP (E-LTP). Moreover, this process was mediated by astrocyte-derived brain-derived neurotrophic factor (BDNF). In contrast, neuron-derived BDNF was critical for both E-LTP and L-LTP. Importantly, the dynamic differences in BDNF secretion play a role in modulating distinct forms of LTP. Moreover, astrocyte- and neuron-derived BDNF exhibited different roles in memory. These observations enriched our knowledge of LTP and memory at the cellular level and implied distinct roles of astrocytes and neurons in information integration.

PV network plasticity mediated by neuregulin1-ErbB4 signalling controls fear extinction.

Neuroplasticity in the medial prefrontal cortex (mPFC) is essential for fear extinction, the process of which forms the basis of the general therapeutic process used to treat human fear disorders. However, the underlying molecules and local circuit elements controlling neuronal activity and concomitant induction of plasticity remain unclear. Here we show that sustained plasticity of the parvalbumin (PV) neuronal network in the infralimbic (IL) mPFC is required for fear extinction in adult male mice and identify the involvement of neuregulin 1-ErbB4 signalling in PV network plasticity-mediated fear extinction. Moreover, regulation of fear extinction by basal medial amygdala (BMA)-projecting IL neurons is dependent on PV network configuration. Together, these results uncover the local molecular circuit mechanisms underlying mPFC-mediated top-down control of fear extinction, suggesting alterative therapeutic approaches to treat fear disorders.

The prevalence of anti-neurofascin-155 antibodies in patients with neuromyelitis optica spectrum disorders.

Anti-neurofascin-155 (NF155) antibodies have been observed in two cases with neuromyelitis optica spectrum disorders (NMOSD). This study investigated the prevalence of anti-NF155 antibodies in patients with NMOSD and the clinical features of anti-NF155 antibody-positive patients. Sera from 129 patients with NMOSD were screened with anti-NF155 antibodies by cell-based assay (CBA) and re-examined using immunostaining of teased mouse sciatic nerve fibres. Fifty-six patients with multiple sclerosis (MS) and 50 healthy controls (HC) were also enrolled for detecting anti-NF155 antibodies. A total of 12.40% (16 of 129) of patients with NMOSD were positive for anti-NF155 antibodies confirmed by both CBA and immunostaining. Immunoglobulin (Ig) G1 was the predominant subclass. However, none of 56 MS patients or 50 HC were positive for anti-NF155 antibodies. Anti-NF155 antibody-positive NMOSD patients had a higher proportion of co-existing with autoimmune diseases (p < 0.001) and higher positive rates of serum non-organ-specific autoantibodies, including anti-SSA antibodies (p < 0.001), anti-SSB antibodies (p = 0.008), anti-Ro-52 antibodies (p < 0.001) and rheumatoid factor (p < 0.001). Five anti-NF155 antibody-positive NMOSD patients who took part in the nerve conduction study showed mildly abnormal results. Differences in some nerve conduction study parameters were observed between anti-NF155 antibody-positive and negative patients. Anti-NF155 antibodies occurred in a small proportion of NMOSD patients. Anti-NF155 antibody-positive NMOSD patients tended to co-exist with autoimmune diseases.

Precision Liver Resection: Three-Dimensional Reconstruction Combined with Fluorescence Laparoscopic Imaging.

Liver surgery has entered the era of precision surgery. Therefore, how to optimize the resection of lesions and reduce the unnecessary time of liver ischemia and hypoxia have become the focus. A total of 11 patients who underwent fluorescence laparoscopic liver mass resection and preoperative three-dimensional (3D) reconstruction between August 2018 and July 2020 were evaluated. Liver cirrhosis occurred in 3 patients. The mean intraoperative blood loss was 166.8 ± 105.7 mL. The average length of the operation time was 152.0 ± 45.3 minutes. The average intraoperative hilar occlusion time was 9.3 minutes (except for hilar cholangiocarcinoma). The liver function of all patients, except patients with hilar bile duct carcinoma, returned to the preoperative level at 72 hours, and no serious complications occurred. 3D reconstruction combined with fluorescence laparoscopic imaging is safe and effective for precision liver resection.

erbb4 Deficits in Chandelier Cells of the Medial Prefrontal Cortex Confer Cognitive Dysfunctions: Implications for Schizophrenia.

erbb4 is a known susceptibility gene for schizophrenia. Chandelier cells (ChCs, also known as axo-axonic cells) are a distinct GABAergic interneuron subtype that exclusively target the axonal initial segment, which is the site of pyramidal neuron action potential initiation. ChCs are a source of ErbB4 expression and alterations in ChC-pyramidal neuron connectivity occur in the medial prefrontal cortex (mPFC) of schizophrenic patients and animal models of schizophrenia. However, the contribution of ErbB4 in mPFC ChCs to the pathogenesis of schizophrenia remains unknown. By conditional deletion or knockdown of ErbB4 from mPFC ChCs, we demonstrated that ErbB4 deficits led to impaired ChC-pyramidal neuron connections and cognitive dysfunctions. Furthermore, the cognitive dysfunctions were normalized by L-838417, an agonist of GABAAα2 receptors enriched in the axonal initial segment. Given that cognitive dysfunctions are a core symptom of schizophrenia, our results may provide a new perspective for understanding the etiology of schizophrenia and suggest that GABAAα2 receptors may be potential pharmacological targets for its treatment.

Molecular evidence of Babesia in pet cats in mainland China.

BACKGROUND: Babesia spp. are important emerging tick-borne protozoan hemoparasites, and pose a great impact on companion animals. Canine babesiosis has been well described worldwide, while felis babesiosis has primarily been reported from South Africa. To the best of our knowledge, Babesia spp. infections in dogs have been well elucidated in pet dog population in China, no report about Babesia spp. infection in cat population in mainland China. RESULTS: In this study, a total of 203 blood samples were collected from pet cats in Shenzhen city, and detected the presence of Babesia spp. with nested-PCR. Sequence comparison based on the 18S rRNA gene and ITS region revealed that three cats (1.48%) were infected with Babesia. vogeli. Notably, the sequences of ITS region obtained in this study shared the highest nucleotide identity with the sequence of B. vogeli strain isolated in cat from Taiwan. CONCLUSIONS: This study is the first report about babesiosis in domestic cats, and also provides molecular evidence of Babesia spp. infection in cat in mainland China. The data present in this study suggest B. vogeli may be circulating in cat population in mainland China. Further study to investigate the epidemiology of Babesia infection in cat nationwide is warranted.

Meta-transcriptomic analysis reveals a new subtype of genotype 3 avian hepatitis E virus in chicken flocks with high mortality in Guangdong, China.

BACKGROUND: Hepatitis E virus (HEV) is one of most important zoonotic viruses, and it can infect a wide range of host species. Avian HEV has been identified as the aetiological agent of big liver and spleen disease or hepatitis-splenomegaly syndrome in chickens. HEV infection is common among chicken flocks in China, and there are currently no practical measures for preventing the spread of the disease. The predominant avian HEV genotype circulating in China have been identified as genotype 3 strains, although some novel genotypes have also been identified from chicken flocks in China. RESULTS: In this study, we used a meta-transcriptomics approach to identify a new subtype of genotype 3 avian HEV in broiler chickens at a poultry farm located in Shenzhen, Guangdong Province, China. The complete genome sequence of the avian HEV, designated CaHEV-GDSZ01, is 6655-nt long, including a 5' UTR of 24 nt and a 3' UTR of 125 nt (excluding the poly(A) tail), and contains three open reading frames (ORFs). Sequence analysis indicated that the complete ORF1 (4599 nt/1532 aa), ORF2 (1821 nt/606 aa) and ORF3 (264 nt/87 aa) of CaHEV-GDSZ01 share the highest nucleotide sequence identity (85.8, 86.7 and 95.8%, respectively) with the corresponding ORFs of genotype 3 avian HEV. Phylogenetic analyses further demonstrated that the avian HEV identified in this study is a new subtype of genotype 3 avian HEV. CONCLUSIONS: Our results demonstrate that a new subtype of genotype 3 avian HEV is endemic in Guangdong, China, and could cause high mortality in infected chickens. This study also provides full genomic data for better understanding the evolutionary relationships of avian HEV circulating in China. Altogether, the results presented in this study suggest that more attention should be paid to avian HEV and its potential disease manifestation.

Molecular characterization of two novel reoviruses isolated from Muscovy ducklings in Guangdong, China.

BACKGROUND: Novel Muscovy duck reovirus (N-MDRV), emerged in southeast China in 2002, which can infect a wide range of waterfowl and induces clinical signs and cytopathic effects that are distinct from those of classical MDRV, and continues to cause high morbidity and 5-50% mortality in ducklings. The present study aimed to investigate the characteristics of two novel reoviruses isolated from Muscovy ducklings in Guangdong, China. RESULTS: Two novel MDRV strains, designated as MDRV-SH12 and MDRV-DH13, were isolated from two diseased Muscovy ducklings in Guangdong province, China in June 2012 and September 2013, respectively. Sequencing of the complete genomes of these two viruses showed that they consisted of 23,418 bp and were divided into 10 segments, ranging from 1191 bp (S4) to 3959 bp (L1) in length, and all segments contained conserved sequences in the 5' non-coding region (GCUUUU) and 3' non-coding region (UCAUC). Pairwise sequence comparisons demonstrated that MDRV-SH12 and MDRV-DH13 showed the highest similarity with novel MDRVs. Phylogenetic analyses of the nucleotide sequences of all 10 segments revealed that MDRV-SH12 and MDRV-DH13 were clustered together with other novel waterfowl-origin reoviruses and were distinct from classical waterfowl-origin and chicken-origin reoviruses. The analyses also showed possible genetic re-assortment events in segment M2 between waterfowl-origin and chicken-origin reoviruses and the segments encoding λA, µA, µNS, σA, and σNS between classical and novel waterfowl-origin reoviruses. Potential recombination events detection in segment S2 suggests that MDRV-SH12 and MDRV-DH13 may be recombinants of classical and novel WRVs. CONCLUSIONS: The results presented in this study, the full genomic data for two novel MDRV strains, will improve our understanding of the evolutionary relationships among the waterfowl-origin reoviruses circulating in China, and may aid in the development of more effective vaccines against various waterfowl-origin reoviruses.

[Effect of golden-hour body temperature bundle management on admission temperature and clinical outcome in preterm infants after birth].

OBJECTIVE: To study the effect of golden-hour body temperature bundle management strategy on admission temperature and clinical outcome in preterm infants with a gestational age of <34 weeks after birth. METHODS: The preterm infants who were born in the delivery room of the West China Second University Hospital of Sichuan University and admitted to the department of neonatology of this hospital within 1 hour after birth from December 2015 to June 2016 and from January to May, 2017 were enrolled. The 173 preterm infants who were admitted from January to May, 2017 were enrolled as the intervention group and were given golden-hour body temperature bundle management. The 164 preterm infants who were admitted from December 2015 to June 2016 were enrolled as the control group and were given conventional body temperature management. RESULTS: The intervention group had a significantly higher mean admission temperature than the control group (36.4±0.4°C vs 35.3±0.6°C; P<0.001). The incidence rate of hypothermia on admission in the intervention group was significantly lower than that in the control group (56.6% vs 97.6%; P<0.001). The intervention group had a significantly lower incidence rate of intracranial hemorrhage within one week after admission than the control group (15.0% vs 31.7%; P<0.05). CONCLUSIONS: Golden-hour body temperature bundle management for preterm infants within one hour after birth can reduce the incidence of hypothermia on admission and improve clinical outcome.

[Identification of chemical constituents in Yangxue Qingnao granule by UPLC-Q-TOF/MS~E].

In order to clarify the chemical constituents in Yangxue Qingnao granule, we established a rapid ultra-performance liquid chromatography/orthogonal acceleration time-of-flight mass spectrometry (UPLC-Q-TOF/MS(E)) method. According to the high resolution MS spectra data, fragmentation ion information and retention time,142 peaks were identified or tentatively presumed by comparison with reference standards data and literature reports. The herbal sources of these peaks were assigned. The results implied that phenolic acids, alkaloids, anthraquinones, phthalides, monoterpene glycosides were included in the main components of Yangxue Qingnao granule. The method is rapid for systematically elucidation of the constituents of Yangxue Qingnao granule and the results would facilitate the quality control of Yangxue Qingnao granule for safe and efficacious use.

[Chemical constituents from endophyte Chaetomium globosum in Imperata cylindrical].

Isolation and purification of chemical constituents from solid culture of endophyte Chaetomium globosum in Imperata cylindrical was performed through silica gel column chromatography, gel filtration over Sephadex LH-20 and preparative HPLC. Nine compounds were obtained and their structures were determined as chaetoglobosin F(1), chaetoglobosin Fex(2), chaetoglobosin E(3) cytoglobosin A(4), penochalasin C(S), isochaetoglobosin D (6), N-benzoylphenylalaninyl-N-benzoyphenylalaninate(7), uracil(8) and 5-methyluracil(9), respectively, based on HR-MS and NMR data and comparison with literatures. Compound 7 was isolated from Chaeeomium sp. for the first time. In vitro cytotoxicity of compounds was evaluated using MTT mothed and 1,3,4 and 5 showed inhibition activity to the human cervical carcinoma cell HeLa with IC50 values of 99.43, 23.77, 97.92, 86.25 micromol x L(-1), while positive cotolocisnin Ad apno1ch alse IC50 24.33 micromol x L(-1).

Astrocytic adenosine 5'-triphosphate release regulates the proliferation of neural stem cells in the adult hippocampus.

Astrocytes are key components of the niche for neural stem cells (NSCs) in the adult hippocampus and play a vital role in regulating NSC proliferation and differentiation. However, the exact molecular mechanisms by which astrocytes modulate NSC proliferation have not been identified. Here, we identified adenosine 5'-triphosphate (ATP) as a proliferative factor required for astrocyte-mediated proliferation of NSCs in the adult hippocampus. Our results indicate that ATP is necessary and sufficient for astrocytes to promote NSC proliferation in vitro. The lack of inositol 1,4,5-trisphosphate receptor type 2 and transgenic blockage of vesicular gliotransmission induced deficient ATP release from astrocytes. This deficiency led to a dysfunction in NSC proliferation that could be rescued via the administration of exogenous ATP. Moreover, P2Y1-mediated purinergic signaling is involved in the astrocyte promotion of NSC proliferation. As adult hippocampal neurogenesis is potentially involved in major mood disorder, our results might offer mechanistic insights into this disease.

Using an autologistic regression model to identify spatial risk factors and spatial risk patterns of hand, foot and mouth disease (HFMD) in Mainland China.

BACKGROUND: There have been large-scale outbreaks of hand, foot and mouth disease (HFMD) in Mainland China over the last decade. These events varied greatly across the country. It is necessary to identify the spatial risk factors and spatial distribution patterns of HFMD for public health control and prevention. Climate risk factors associated with HFMD occurrence have been recognized. However, few studies discussed the socio-economic determinants of HFMD risk at a space scale. METHODS: HFMD records in Mainland China in May 2008 were collected. Both climate and socio-economic factors were selected as potential risk exposures of HFMD. Odds ratio (OR) was used to identify the spatial risk factors. A spatial autologistic regression model was employed to get OR values of each exposures and model the spatial distribution patterns of HFMD risk. RESULTS: Results showed that both climate and socio-economic variables were spatial risk factors for HFMD transmission in Mainland China. The statistically significant risk factors are monthly average precipitation (OR = 1.4354), monthly average temperature (OR = 1.379), monthly average wind speed (OR = 1.186), the number of industrial enterprises above designated size (OR = 17.699), the population density (OR = 1.953), and the proportion of student population (OR = 1.286). The spatial autologistic regression model has a good goodness of fit (ROC = 0.817) and prediction accuracy (Correct ratio = 78.45%) of HFMD occurrence. The autologistic regression model also reduces the contribution of the residual term in the ordinary logistic regression model significantly, from 17.25 to 1.25 for the odds ratio. Based on the prediction results of the spatial model, we obtained a map of the probability of HFMD occurrence that shows the spatial distribution pattern and local epidemic risk over Mainland China. CONCLUSIONS: The autologistic regression model was used to identify spatial risk factors and model spatial risk patterns of HFMD. HFMD occurrences were found to be spatially heterogeneous over the Mainland China, which is related to both the climate and socio-economic variables. The combination of socio-economic and climate exposures can explain the HFMD occurrences more comprehensively and objectively than those with only climate exposures. The modeled probability of HFMD occurrence at the county level reveals not only the spatial trends, but also the local details of epidemic risk, even in the regions where there were no HFMD case records.

Anticonvulsant activity of acute and chronic treatment with a-asarone from Acorus gramineus in seizure models.

For centuries, extracts of Acorus gramineus have been used extensively in traditional Chinese medicine for the treatment, management, and/or control of human ailments, including central nervous system disorders such as convulsions and epilepsy. In the present study, we investigated the anticonvulsant activity of chronic treatment with the plant's major essential oil component (a-asarone, 50-200 mg/kg, per os (p.o.)) against maximal electroshock seizure (MES), pentylenetetrazole (PTZ)-induced seizures in mice, lithium-pilocarpine (LI-PILO)-induced status epilepticus (SE), and spontaneous recurrent seizures (SRSs) in rats and determined whether a single acute administration of a-asarone at various doses could produce anticonvulsant activity. As the standard antiepileptic drugs used, chronically administered a-asarone (50-200 mg/kg, p.o.) significantly delayed (p<0.05) the onset of, and antagonized maximal electroshock seizure and PTZ-induced seizures. Chronically administered a-asarone (50-200 mg/kg) also profoundly antagonized LI-PILO-induced seizures. The SE incidence, SE latency and seizure severity as well as mortality were significantly reduced after treatment with a-asarone at different doses. Higher doses of a-asarone (100-200 mg/kg) significantly reduced spontaneous recurrent seizure incidence, severity, and seizure frequency during treatment in LI-PILO-induced SRSs rats. On the other hand, a single acute administration of a-asarone (50-200 mg/kg) produced weak anticonvulsant activity in MES and PTZ-induced seizures. The results of this laboratory animal study indicate that chronically administered a-asarone possesses anticonvulsant activity in the mammalian experimental model used, and thus suggest that a-asarone may be used as a natural supplementary remedy in the management of convulsions and epilepsy.

[Temporal variation analysis for spectral reflectance of maize leaves using a fitting method].

The present study is to investigate the temporal variation patterns through the dataset of spectral reflectance of maize leaf using a fitting method. In the field experiment, 1 261 pieces of spectral reflectance of maize leaves at different leaf positions were measured every day during its life cycle. After signal/noise analysis, the visible and near infrared (VNIR) band (400-960 nm) was selected in this study. The spectral reflectance was fitted using a spectral scatter diagram (SSD) method. Seven fitting coefficients were employed to denote the temporal variation patterns of maize leaf, which can also be fitted by bi-variate quadratic functions. The comparison of the fitted results with the original measurement data shows that the fitting results are reasonably good, where for 98.7% leaves r is larger than 0.99, and for 80.9% leaves RMSE is less than 0.001 5. All the fitted spectral reflectance is compared with the original measurement data, where r is 0.997 8, and RMSE is 0.0105. The results show that this method is particularly suitable for presenting the temporal variation patterns of the spectral reflectance of maize leaves.

TM4SF1 upregulates MYH9 to activate the NOTCH pathway to promote cancer stemness and lenvatinib resistance in HCC.

TM4SF1, a member of the transmembrane 4 superfamily, is crucial for both healthy and malignant human tissues. The significant function of TM4SF1 in the incidence and progression of cancer has been widely recognized in recent years. Although some achievements have been made in the study of TM4SF1, the effect of TM4SF1 on cancer stemness in hepatocellular carcinoma (HCC) and its molecular basis are yet to be reported. We found through abundant in vitro and in vivo experiments which the expression of TM4SF1 was positively correlated with the progression and cancer stemness of HCC. We identified the downstream protein MYH9 of TM4SF1 and its final regulatory target NOTCH pathway using bioinformatics analysis and protein mass spectrometry. We cultivated a Lenvatinib-resistant strain from HCC cells to examine the relationship between cancer stemness and tumor drug resistance. The study confirmed that TM4SF1 could regulate the NOTCH pathway by upregulating MYH9, thus promoting cancer stemness and Lenvatinib resistance in HCC. This study not only provided a new idea for the pathogenesis of HCC but also confirmed that TM4SF1 might become a new intervention point to improve the clinical efficacy of Lenvatinib in treating HCC.