Rediscovery and systematics of the enigmatic genus Helicostoa reveals a new species of sessile freshwater snail with remarkable sexual dimorphism.

Helicostoa sinensis E. Lamy, 1926 is a unique freshwater gastropod species with a sessile habit. This enigmatic species was first found cemented on river limestones from China about 120 years ago and described together with the genus. It was never collected again and has been considered monotypic. Here, we report the rediscovery of Helicostoa from several rivers in China, and describe a second species of this genus based on a comprehensive study. In addition to the unique sessile habit of both species, the new Helicostoa species presents one of the most remarkable cases of sexual dimorphism within molluscs. Only the adult female is sessile and the original aperture of the female is sealed by shell matter or rock, while an opening on the body whorl takes the function of the original aperture. The male is vagile, with a normal aperture. Our results confirm the recently suggested placement of Helicostoa within the family Bithyniidae. The sessility of Helicostoa species is considered as an adaption to the limestone habitat in large rivers. The extreme sexual dimorphism and secondary aperture of females are considered as adaptations to overcome the obstacles for mating and feeding that come with a sessile life style.

Identification of lignans as ATP citrate lyase (ACLY) inhibitors from the roots of Pouzolzia zeylanica.

A new lignan, named pouzolignan P (1), together with 14 known ones (2 - 15) were isolated from the roots of Pouzolzia zeylanica (L.) Benn. Their structures were deduced based on the detailed spectroscopic analysis. All the isolates were evaluated for their inhibitory activities toward the ATP citrate lyase (ACLY). Among them, four lignans, isopouzolignan K (3), gnemontanins E (5), gnetuhainin I (6), and styraxlignolide D (15) showed excellent ACLY inhibitory effect with IC50 values of 9.06, 0.59, 2.63, and 7.62 µM, respectively. These compounds were further evaluated for their cholesterol-lowing effects on ox-LDL-induced high-cholesterol HepG2 cells. Compound 15 emerges as the most potent ACLY inhibitor, which significantly decreased the TC level in a dose-dependent manner. In addition, molecular docking simulations elucidated that 15 formed a strong hydrogen-bond interaction with Glu599 of ACLY, which was an important site responsible for the enzyme catalytic activity.

Altered fear engram encoding underlying conditioned versus unconditioned stimulus-initiated memory updating.

It is known that post-retrieval extinction but not extinction alone could erase fear memory. However, whether the coding pattern of original fear engrams is remodeled or inhibited remains largely unclear. We found increased reactivation of engram cells in the prelimbic cortex and basolateral amygdala during memory updating. Moreover, conditioned stimulus- and unconditioned stimulus-initiated memory updating depends on the engram cell reactivation in the prelimbic cortex and basolateral amygdala, respectively. Last, we found that memory updating causes increased overlapping between fear and extinction cells, and the original fear engram encoding was altered during memory updating. Our data provide the first evidence to show the overlapping ensembles between fear and extinction cells and the functional reorganization of original engrams underlying conditioned stimulus- and unconditioned stimulus-initiated memory updating.

Integrative taxonomy revealing a troglobitic new genus of Diplommatinidae from Jiangxi, China (Gastropoda: Caenogastropoda: Cyclophoroidea).

A new subterranean diplommatinid snail is described and illustrated from Jiangxi, China. The species is diagnosed by its cylindrical-fusiform shell and absence of internal columellar lamellae and parietal folds. The morphological and molecular phylogenetic characterization of the new species supports the erection of a new genus, Sohtsuia Z.-Y. Chen, gen. nov. A molecular phylogeny of representative East Asian continental species of Diplommatina Benson, 1949 is provided and the relationships of the new genus are discussed. Sohtsuia diting sp. nov. is described as new species.

Electroacupuncture alleviates depression-like behaviours via a neural mechanism involving activation of Nucleus Accumbens Shell.

OBJECTIVES: This study investigated the effects of electroacupuncture (EA) on the depression-like behaviours in a mouse model of chronic restraint stress (CRS) and explored the underlying neural mechanisms. METHODS: Depression-like behaviours including sucrose preference test (SPT), open field test (OFT) and tail suspension test (TST) were carried out to evaluate the effects of CRS and EA treatment. Using immunohistochemistry to measure the expression of c-Fos. The Nucleus Accumbens Shell (NAc Shell) in C57BL/6J mice were activated or inhibited using Chemogenetics. RESULTS: All the CRS stimulated groups showed lower sucrose preference in the SPT and decreased centre times in the OFT, and increased immobility time in the TST when compared to the normal control. Interestingly, EA at LR3 or HT7 exerted anti-depressant effects, and LR3 EA exhibited a more significant restoration than HT7. Furthermore, EA at LR3 increased expression of c-Fos in the NAc Shell. Chemogenetic inhibition of NAc Shell blocked the effects of EA, whereas enhancement of NAc Shell activity profoundly reversed depressive phenotypes. CONCLUSIONS: LR3 EA was effective in alleviating the depressive-like behaviours, and this therapeutic effect was associated with the activation of NAc Shell. Collectively, these findings revealed that EA may represent a promising therapeutic strategy for depression.

TRPV1 SUMOylation suppresses itch by inhibiting TRPV1 interaction with H1 receptors.

The molecular mechanism underlying the functional interaction between H1R and TRPV1 remains unclear. We show here that H1R directly binds to the carboxy-terminal region of TRPV1 at residues 715-725 and 736-749. Cell-penetrating peptides containing these sequences suppress histamine-induced scratching behavior in a cheek injection model. The H1R-TRPV1 binding is kept at a minimum at rest in mouse trigeminal neurons due to TRPV1 SUMOylation and it is enhanced upon histamine treatment through a transient TRPV1 deSUMOylation. The knockin of the SUMOylation-deficient TRPV1K823R mutant in mice leads to constitutive enhancement of H1R-TRPV1 binding, which exacerbates scratching behaviors induced by histamine. Conversely, SENP1 conditional knockout in sensory neurons enhances TRPV1 SUMOylation and suppresses the histamine-induced scratching response. In addition to interfering with binding, TRPV1 SUMOylation promotes H1R degradation through ubiquitination. Our work unveils the molecular mechanism of histaminergic itch by which H1R directly binds to deSUMOylated TRPV1 to facilitate the transduction of the pruritogen signal to the scratching response.

Comprehensive radiomics nomogram for predicting survival of patients with combined hepatocellular carcinoma and cholangiocarcinoma.

BACKGROUND: Combined hepatocellular carcinoma (HCC) and cholangiocarcinoma (cHCC-CCA) is defined as a single nodule showing differentiation into HCC and intrahepatic cholangiocarcinoma and has a poor prognosis. AIM: To develop a radiomics nomogram for predicting post-resection survival of patients with cHCC-CCA. METHODS: Patients with pathologically diagnosed cHCC-CCA were randomly divided into training and validation sets. Radiomics features were extracted from portal venous phase computed tomography (CT) images using the least absolute shrinkage and selection operator Cox regression and random forest analysis. A nomogram integrating the radiomics score and clinical factors was developed using univariate analysis and multivariate Cox regression. Nomogram performance was assessed in terms of the C-index as well as calibration, decision, and survival curves. RESULTS: CT and clinical data of 118 patients were included in the study. The radiomics score, vascular invasion, anatomical resection, total bilirubin level, and satellite lesions were found to be independent predictors of overall survival (OS) and were therefore included in an integrative nomogram. The nomogram was more strongly associated with OS (hazard ratio: 8.155, 95% confidence interval: 4.498-14.785, P < 0.001) than a model based on the radiomics score or only clinical factors. The area under the curve values for 1-year and 3-year OS in the training set were 0.878 and 0.875, respectively. Patients stratified as being at high risk of poor prognosis showed a significantly shorter median OS than those stratified as being at low risk (6.1 vs 81.6 mo, P < 0.001). CONCLUSION: This nomogram may predict survival of cHCC-CCA patients after hepatectomy and therefore help identify those more likely to benefit from surgery.

Notes on the genus Messageria Bavay amp; Dautzenberg, 1904, with descriptions of a new species and a new subspecies (Gastropoda: Caenogastropoda: Cyclophoroidea: Alycaeidae).

In this study, the systematic status of Messageria Bavay Dautzenberg, 1904 is discussed. It is recognized as an alycaeid genus, rather than as a subgenus or a junior synonym of Helicomorpha Mllendorff, 1890 (Diplommatinidae) as previously thought. Additionally, a new species, Messageria sinica n. sp. from Guizhou, and a new subspecies, Messageria scalarioides donghiana n. ssp. from Guangxi are described. Messageria scalarioides donghiana n. ssp. is morphologically different from the nominate subspecies by the larger shell and wider lower whorls and umbilicus. Messageria sinica n. sp. is morphologically different from the type species by having larger shell and distinct intermediate ribs.

Systematic revision of Stegodera Martens, 1876 (Gastropoda, Stylommatophora, Camaenidae), with description of a new genus.

The monotypic genus Stegodera Martens, 1876 is systematically revised based on anatomical and morphological examination of freshly collected specimens. A new species from southern Hunan, which resembles Stegoderaangusticollis, is confirmed to represent a new genus evidenced by comparative shell morphology and anatomy as well as by molecular phylogenetic analyses. The new genus might be more closely related to Stegodera and Nesiohelix Kuroda & Emura, but differs anatomically from the latter two genera by the absence of a dart apparatus.

Carboxypeptidase E Regulates Activity-Dependent TrkB Neuronal Surface Insertion and Hippocampal Memory.

Activity-dependent insertion of the tropomyosin-related kinase B (TrkB) receptor into the plasma membrane can explain, in part, the preferential effect of brain-derived neurotrophic factor (BDNF) on active neurons and synapses; however, the underlying molecular mechanisms remain obscure. Here, we report a novel function for carboxypeptidase E (CPE) in controlling chemical long-term potentiation stimuli-induced TrkB surface delivery in hippocampal neurons. Total internal reflection fluorescence assays and line plot assays showed that CPE facilitates TrkB transport from dendritic shafts to the plasma membrane. The Box2 domain in the juxtamembrane region of TrkB and the C terminus of CPE are critical for the activity-dependent plasma membrane insertion of TrkB. Moreover, the transactivator of transcription TAT-CPE452-466, which could block the association between CPE and TrkB, significantly inhibited neuronal activity-enhanced BDNF signaling and dendritic spine morphologic plasticity in cultured hippocampal neurons. Microinfusion of TAT-CPE452-466 into the dorsal hippocampus of male C57BL/6 mice inhibited the endogenous interaction between TrkB and CPE and diminished fear-conditioning-induced TrkB phosphorylation, which might lead to an impairment in hippocampal memory acquisition and consolidation but not retrieval. These results suggest that CPE modulates activity-induced TrkB surface insertion and hippocampal-dependent memory and sheds light on our understanding of the role of CPE in TrkB-dependent synaptic plasticity and memory modulation.SIGNIFICANCE STATEMENT It is well known that BDNF acts preferentially on active neurons; however, the underlying molecular mechanism is not fully understood. In this study, we found that the cytoplasmic tail of CPE could interact with TrkB and facilitate the neuronal activity-dependent movement of TrkB vesicles to the plasma membrane. Blocking the association between CPE and TrkB decreased fear-conditioning-induced TrkB phosphorylation and led to hippocampal memory deficits. These findings provide novel insights into the role of CPE in TrkB intracellular trafficking as well as in mediating BDNF/TrkB function in synaptic plasticity and hippocampal memory.

Evidence for an Interaction Between NEDD4 and Childhood Trauma on Clinical Characters of Schizophrenia With Family History of Psychosis.

Background: Neural precursor cell-expressed developmentally downregulated 4 (NEDD4) polymorphisms and childhood trauma (CT) are associated with schizophrenia. However, whether NEDD4 interacts with CT on symptoms of schizophrenia remains unknown. This study aimed to investigate the gene-environment interaction effect. Methods: We recruited 289 schizophrenia patients and 487 controls and genotyped rs2303579, rs3088077, rs7162435, rs11550869, and rs62043855 in their NEDD4 gene. Results: We found significant differences in the rs2303579 and rs3088077 between the two groups. Patients with the rs2303579 CC genotype had higher scores compared with other genotype (P = 0.026) in the test of positive schizophrenia syndrome scores, whereas patients with the rs3088077 TT (P = 0.037) and rs7162435 CC genotypes (P = 0.009) had higher scores compared with the other genotypes in the test of excitement factor. Patients with a family history of psychosis (FH+) reported higher negative scores (P = 0.012) than those without. Patients exposed to physical abuse (PA) reported a lower language learning and memory score (P = 0.017) and working memory score (P = 0.047) than those not. Patients exposed to sexual abuse (SA) reported a lower reasoning and problem-solving skills score (P = 0.025); those exposed to emotional neglect (EN) reported a lower social cognition score (P = 0.044); and those exposed to physical neglect reported a lower social cognition score (P = 0.036) but higher visual learning and memory score (P = 0.032). Rs3088077 could interact with EN to increase risk for schizophrenia. Optimal model rs62043855 × EA, rs3088077 × rs7162435 × rs11550869 × SA × EN and rs2303579 × rs7162435 × rs11550869 × rs62043855 × EA × PA could explain positive symptom, excitement symptom and working memory, respectively, in FH+ group. Conclusion: The study highlighted that the combined interaction of NEDD4 and CT may be associated with symptoms of schizophrenia especially for those with FH+.

The effect and safety of preoperative biliary drainage in patients with hilar cholangiocarcinoma: an updated meta-analysis.

BACKGROUND: The effect and safety of preoperative biliary drainage (PBD) in patients with perihilar cholangiocarcinoma are still controversial; the aim of our study is to evaluate all aspects of PBD. METHODS: All included studies featured PBD versus non-PBD (NPBD) groups were from 1996 to 2019 and were extracted from Cochrane Library, Embase, PubMed, and Science Citation Index Expanded. RESULTS: Sixteen studies met the inclusion criteria and were included in this analysis. PBD may lead to a significantly higher incidence of overall morbidities (OR 0.67, 95% CI 0.53, 0.85; P = 0.0009) and intraoperative transfusions (OR 0.72, 95% CI 0.55, 0.94; P = 0.02); moreover, bile leakage (OR 0.58, 95% CI 0.24, 1.41; P = 0.04), infection (OR 0.31, 95% CI 0.20, 0.47; P < 0.00001), and cholangitis (OR 0.18, 95% CI 0.007, 0.48; P = 0.0007) are also related to PBD. However, NPBD was associated with more frequent hepatic insufficiency (OR 3.09, 95% CI 1.15, 8.31; P = 0.03). In the subgroup meta-analysis, the differences in the outcomes of bile leakage and overall morbidity lost significance between the PBD and NPBD groups when the mean total serum bilirubin (TSB) concentration was above 15 mg/dl. CONCLUSION: Meta-analysis demonstrated that compared to NPBD, PBD is associated with a greater risk of several kinds of infection and morbidities, but its ability to reduce postoperative hepatic insufficiency cannot be ignored. In patients with a high TSB concentration, PBD tends to be a better choice. However, these results need to be confirmed in a future prospective randomized trial with large samples to clarify the effects and find a specific TSB concentration for PBD.

Two new cyclophoroid species from Hubei, China, with proposal of a new genus (Gastropoda, Caenogastropoda, Diplommatinidae and Alycaeidae).

Two new species, Sinoarinia feii Chen, gen. et sp. nov. and Pincerna vallis Chen & Wu, sp. nov., are described from western Hubei, China. The new genus Sinoarinia Chen & Wu, gen. nov. is established based on the strongly constricted penultimate whorl and the ascending last whorl. The Vietnamese species Pincerna costulosa (Bavay & Dautzenberg) is newly reported from Yunnan, China. For comparison, photographs of the shells of closely related species are provided. A key to the known species of Sinoarinia gen. nov. is included.

The neuroprotective and neurorestorative effects of growth differentiation factor 11 in cerebral ischemic injury.

Growth differentiation factor 11 (GDF11), a member of the transforming growth factor-ß (TGF-ß) superfamily, regulates various biological processes in mammals. The effect of GDF11 in brain injury has not been fully elucidated. Our aim was to investigate the effects of GDF11 in cerebral ischemic injury. The expression level of GDF11 increased significantly in the peri-infarct cerebral cortex. Next, the effect of the intracerebroventricular injection of a GDF11 overexpression lentivirus or rGDF11 was investigated in middle cerebral artery occlusion (MCAO) rats. The preventative effects of the GDF11 overexpression virus on stroke were observed. The delivery of the lentivirus into rats before MCAO significantly reduced the infarct volume and the percentage of apoptotic cells and improved motor function in MCAO rats. Furthermore, it elevated the expression of p-Smad2/3 and promoted neurogenesis and angiogenesis in the ipsilateral SVZ during ischemic injury. More importantly, the therapeutic effects of rGDF11 on stroke were subsequently explored. The results in MCAO rats treated with rGDF11 were found similar to that in those treated with the GDF11 overexpression lentivirus. Together, these findings indicate that GDF11 has neuroprotective and neurorestorative effects in cerebral ischemic injury and provide new insights into the function and mechanism of GDF11 in stroke models.

Parenchymal-sparing versus extended hepatectomy for colorectal liver metastases: A systematic review and meta-analysis.

AIMS: To assess the safety and efficacy of parenchymal-sparing hepatectomy (PSH) as a treatment of colorectal liver metastases (CLM). METHODS: A comprehensive medical literature search was performed. Perioperative and long-term survival outcomes were pooled. Subgroup analysis and meta-regression analysis were performed to identify potential sources of heterogeneity. RESULTS: A total of 18 studies comprising 7081 CLM patients were eligible for this study. The PSH was performed on 3974 (56.1%) patients. We found that the OS (overall survival; hazard ratio [HR] = 1.01, 95% confidence interval [CI]: 0.94-1.08) and RFS (recurrence-free survival; HR = 1.00, 95% CI: 0.94-1.07) were comparable between non-PSH and PSH group. The perioperative outcomes were better in PSH than in non-PSH group. Non-PSH group was significantly associated with longer operative time (standard mean difference [SMD] = 1.17, 95% CI: 0.33-2.00), increased estimated blood loss (SMD = 1.36, 95% CI: 0.64-2.07), higher intraoperative transfusion rate (risk ratio [RR] = 2.27, 95% CI: 1.60-3.23), and more postoperative complications (RR = 1.39, 95% CI: 1.16-1.66). Meta-regression analyses revealed that no variable influenced the association between surgical types and the survival outcomes. CONCLUSIONS: This study shows that PSH is associated with better perioperative outcomes without compromising oncological outcomes. Given the increasing incidence of hepatic parenchyma, the PSH treatment offers a greater opportunity of repeat resection for intrahepatic recurrent tumors. It should be considered as an effective surgical approach for CLM.

Long non-coding RNA PlncRNA-1 promotes cell proliferation and hepatic metastasis in colorectal cancer.

Emerging evidence has identified that long non-coding RNAs (lncRNAs) may play an important role in the pathogenesis of many cancer types, including colorectal cancer (CRC). However, the role of PlncRNA-1 in CRC remains unclear. The aim of our present study was to investigate the potential functions of PlncRNA-1 in CRC and to identify the underlying mechanisms of action. We demonstrated that up-regulated PlncRNA-1 in CRC tissues and cells promoted cell proliferation by accelerating cell cycle process and inhibiting cell apoptosis in vitro, enhanced tumor growth and matastasis in vivo and was associated with cell migration and invasion, EMT process of CRC cells. In addition, PlncRNA-1 was a target of miR-204 and enhanced the expression of an endogenous miR-204 target, MMP9 in CRC cells. Furthermore, we found that PlncRNA-1 activates Wnt/ß-catenin pathway through the miR-204 in CRC cells. These results suggest that the PlncRNA-1/miR-204/ Wnt/ß-catenin regulatory network may shed light on tumorigenesis in CRC.

Elevating Integrin-linked Kinase expression has rescued hippocampal neurogenesis and memory deficits in an AD animal model.

Alterations in adult neurogenesis have been regarded as a major cause of cognitive impairment in Alzheimer's disease (AD). The underlying mechanism of neurogenesis deficiency in AD remains unclear. In this study, we reported that Integrin-linked Kinase (ILK) protein levels and phosphorylation were significantly decreased in the hippocampus of APP/PS1 mice. Increased ILK expression of dentate gyrus (DG) rescued the hippocampus-dependent neurogenesis and memory deficits in APP/PS1 mice. Moreover, we demonstrated that the effect of ILK overexpression in the hippocampus was exerted via AKT-GSK3ß pathway. Finally, we found that Fluoxetine, a selective serotonin reuptake inhibitor, could improve the impaired hippocampal neurogenesis and memory by enhancing ILK-AKT-GSK3ß pathway activity in APP/PS1 mice. Thus, these findings demonstrated the effects of ILK on neurogenesis and memory recovery, suggesting that ILK is an important therapeutic target for AD prevention and treatment.

The choose of different surgical therapies of hepatic alveolar echinococcosis: A single-center retrospective case-control study.

The aim of this study was to evaluate different surgical therapies for hepatic alveolar echinococcosis in different clinical stages.We analyze the clinical data of 115 patients who received surgical treatment in West China Hospital from January 2004 to June 2016. Among these patients, 77 cases underwent radical hepatic resection (group A, n = 77); 17 cases underwent palliative resection (group B, n = 17), and 21 cases underwent liver transplantation (group C, n = 21) with 12 cases of orthotopic liver transplantation and 9 cases of liver autotransplantation.The postoperative complication rate of radical hepatic resection group was 13.0% (10/77), which is statistically significant (P < .05) than the rate of palliative resection group 29.4% (5/17) or liver transplantation group 23.8% (5/21). The follow-up period ranged from 1 to 72 months. The overall median survival rate of radical resection was 72/77, higher than the rate of palliative group (12/17) or transplantation group (17/21), which was also statistically significant (P < .01).In our study, we believe in that all stages of hepatic alveolar echinococcosis should take active surgical interventions, and radical hepatic resection should be considered as the first-choice treatment for early stage of alveolar echinococcosis, while palliative surgery is still helpful to relieve symptoms and improve the life quality for advanced patients. Liver transplantation might also be an alternative option for the late-stage hepatic alveolar echinococcosis.

Uhrf2 deletion impairs the formation of hippocampus-dependent memory by changing the structure of the dentate gyrus.

Ubiquitin-like with PHD and ring finger domains 2 (Uhrf2) is distributed in many brain regions, including the cortex and hippocampus. Decreased Uhrf2 expression is involved in neurodegenerative disease. A recent study showed Uhrf2 deletion impaired spatial memory; however, the mechanism remains elusive. In our study, we determined that Uhrf2+/- and Uhrf2-/- mice had significant learning and memory deficiencies in contextual fear conditioning (CFC) and the novel place recognition test but not in the novel object recognition test. Interestingly, there were no changes in the Uhrf2 protein levels in the hippocampus of C57BL6 mice after CFC training, which suggests Uhrf2 in adult mice may not be related to the formation of CFC long-term memory. Based on Nissl staining, Uhrf2 deletion caused neuropathological changes specifically in the crest of the dentate gyrus (DG), such as cell swelling, a vague outline and confused boundary; however, no changes were identified in the medial prefrontal cortex (mPFC). Transmission electron microscope assay further indicated a series of abnormal ultrastructure changes in neurons and glia in the DG crest. These results suggested that Uhrf2 deletion selectively blocked the development of the DG crest and impaired hippocampus-dependent learning and memory. Our study will facilitate a better understanding of the role of Uhrf2 protein in the central nervous system.