Substantia Innominata Glutamatergic Neurons Modulate Sevoflurane Anesthesia in Male Mice.

BACKGROUND: Accumulated evidence suggests that brain regions that promote wakefulness also facilitate emergence from general anesthesia (GA). Glutamatergic neurons in the substantia innominata (SI) regulate motivation-related aversive, depressive, and aggressive behaviors relying on heightened arousal. Here, we hypothesize that glutamatergic neurons in the SI are also involved in the regulation of the effects of sevoflurane anesthesia. METHODS: With a combination of fiber photometry, chemogenetic and optogenetic tools, behavioral tests, and cortical electroencephalogram recordings, we investigated whether and how SI glutamatergic neurons and their projections to the lateral hypothalamus (LH) regulate sevoflurane anesthesia in adult male mice. RESULTS: Population activity of glutamatergic neurons in the SI gradually decreased upon sevoflurane-induced loss of consciousness (LOC) and slowly returned as soon as inhalation of sevoflurane discontinued before recovery of consciousness (ROC). Chemogenetic activation of SI glutamatergic neurons dampened the animals' sensitivity to sevoflurane exposure, prolonged induction time (mean ± standard deviation [SD]; 389 ± 67 seconds vs 458 ± 53 seconds; P = .047), and shortened emergence time (305 seconds, 95% confidence interval [CI], 242-369 seconds vs 207 seconds, 95% CI, 135-279 seconds; P = .004), whereas chemogenetic inhibition of these neurons facilitated sevoflurane anesthesia. Furthermore, optogenetic activation of SI glutamatergic neurons and their terminals in LH induced cortical activation and behavioral emergence from different depths of sevoflurane anesthesia. CONCLUSIONS: Our study shows that SI glutamatergic neuronal activity facilitates emergence from sevoflurane anesthesia and provides evidence for the involvement of the SI-LH glutamatergic pathway in the regulation of consciousness during GA.

Oxytocin and the Punitive Hub-Dynamic Spread of Cooperation in Human Social Networks.

Human society operates on large-scale cooperation. However, individual differences in cooperativeness and incentives to free ride on others' cooperation make large-scale cooperation fragile and can lead to reduced social welfare. Thus, how individual cooperation spreads through human social networks remains puzzling from ecological, evolutionary, and societal perspectives. Here, we identify oxytocin and costly punishment as biobehavioral mechanisms that facilitate the propagation of cooperation in social networks. In three laboratory experiments (n = 870 human participants: 373 males, 497 females), individuals were embedded in heterogeneous networks and made repeated decisions with feedback in games of trust (n = 342), ultimatum bargaining (n = 324), and prisoner's dilemma with punishment (n = 204). In each heterogeneous network, individuals at central positions (hub nodes) were given intranasal oxytocin (or placebo). Giving oxytocin (vs matching placebo) to central individuals increased their trust and enforcement of cooperation norms. Oxytocin-enhanced norm enforcement, but not elevated trust, explained the spreading of cooperation throughout the social network. Moreover, grounded in evolutionary game theory, we simulated computer agents that interacted in heterogeneous networks with central nodes varying in terms of cooperation and punishment levels. Simulation results confirmed that central cooperators' willingness to punish noncooperation allowed the permeation of the network and enabled the evolution of network cooperation. These results identify an oxytocin-initiated proximate mechanism explaining how individual cooperation facilitates network-wide cooperation in human society and shed light on the widespread phenomenon of heterogeneous composition and enforcement systems at all levels of life.SIGNIFICANCE STATEMENT Human society operates on large-scale cooperation. Yet because cooperation is exploitable by free riding, how cooperation in social networks emerges remains puzzling from evolutionary and societal perspectives. Here we identify oxytocin and altruistic punishment as key factors facilitating the propagation of cooperation in human social networks. Individuals played repeated economic games in heterogeneous networks where individuals at central positions were given oxytocin or placebo. Oxytocin-enhanced cooperative norm enforcement, but not elevated trust, explained cooperation spreading throughout the social network. Evolutionary simulations confirmed that central cooperators' willingness to punish noncooperation allowed the permeation of the network and enabled the evolution of cooperation. These results identify an oxytocin-initiated proximate mechanism explaining how individual cooperation facilitates network-wide cooperation in human social networks.

Ultrasensitive and Quantitative DNA Methylation Detection Method Based on the MutS Protein.

DNA methylation is closely related to cancer. It is generally accepted that DNA methylation detection is crucial in cancer diagnosis, prognosis, and treatment monitoring. Therefore, there is an urgent demand for developing a simple, rapid, highly sensitive, and highly specific methylation detection method to detect DNA methylation at specific sites quantitatively. In this work, we introduce a DNA methylation detection method based on MutS and methylation-specific PCR, named MutS-based methylation-specific PCR (MB-MSP), which has the advantages of simplicity, speed, high specificity, sensitivity, and broad applicability. Utilizing the MutS's ability to bind mismatched base pairs, we inhibit not only the amplification of unmethylated DNA but also nonspecific primer amplification. We achieved a detection sensitivity of 0.5% for the methylated genes of ACP1, CLEC11A, and SEPT9 by MB-MSP. It has a good linear relationship and a detection time of only 1.5 h. To validate the feasibility of the MB-MSP method in clinical application, we conducted methylation detection on plasma-circulating tumor DNA samples from 10 liver cancer patients and 5 healthy people, achieving a 100% accuracy rate. In conclusion, MB-MSP, as a novel and reliable DNA methylation detection tool, holds significant application value and potential for advancing early cancer diagnosis.

Circ_0002295 facilitated myocardial fibrosis progression through the miR-1287/CXCR2 axis.

Myocardial fibrosis (MF) is involved in hypertension, myocardial infarction and heart failure. It has been reported that circular RNA (circRNA) is a key regulatory factor of MF progression. In this study, we revealed that circ_0002295 and CXCR2 were elevated, and miR-1287 was reduced in MF patients. Knockdown of circ_0002295 effectively suppressed the proliferation, migration and MF progression. Circ_0002295 was the molecular sponge of miR-12878, and miR-1287 inhibitor reversed the biological functions of circ_0002295 on the myocardial fibrosis. CXCR2 was a target gene of miR-1287, and CXCR2 silencing relieved the impacts of miR-1287 inhibitor on cardiac myofibroblasts. Circ_0002295 promoted MF progression by regulating the miR-1287/CXCR2 axis, providing a possible circRNA-targeted therapy for MF.

Silencing GmATG7 Leads to Accelerated Senescence and Enhanced Disease Resistance in Soybean.

Autophagy plays a critical role in nutrient recycling/re-utilizing under nutrient deprivation conditions. However, the role of autophagy in soybeans has not been intensively investigated. In this study, the Autophay-related gene 7 (ATG7) gene in soybeans (referred to as GmATG7) was silenced using a virus-induced gene silencing approach mediated by Bean pod mottle virus (BPMV). Our results showed that ATG8 proteins were highly accumulated in the dark-treated leaves of the GmATG7-silenced plants relative to the vector control leaves (BPMV-0), which is indicative of an impaired autophagy pathway. Consistent with the impaired autophagy, the dark-treated GmATG7-silenced leaves displayed an accelerated senescence phenotype, which was not seen on the dark-treated BPMV-0 leaves. In addition, the accumulation levels of both H2O2 and salicylic acid (SA) were significantly induced in the GmATG7-silenced plants compared with the BPMV-0 plants, indicating an activated immunity. Consistently, the GmATG7-silenced plants were more resistant against both Pseudomonas syringae pv. glycinea (Psg) and Soybean mosaic virus (SMV) compared with the BPMV-0 plants. However, the activated immunity in the GmATG7-silenced plant was not dependent upon the activation of MPK3/MPK6. Collectively, our results demonstrated that the function of GmATG7 is indispensable for autophagy in soybeans, and the activated immunity in the GmATG7-silenced plant is a result of impaired autophagy.

[A new allo-aromadendrane sesquiterpene from Dendrobium nobile].

To study the chemical constituents in the non-alkaloid part of stems of Dendrobium nobile. The macroporous adsorption resin, MCI, silica gel, RP-C_(18), and Sephadex LH-20 gel, preparative thin layer chromatography, and preparative high-performance liquid chromatography(HPLC) were used to isolate and purify the compounds. The structures of the compound were determined according to the spectra data, physicochemical properties, and relevant references. A total of 8 compounds were isolated from D. nobile, which were soltorvum F(1), p-hydroxyphenylpropionic acid(2), vanillic acid(3), p-hydroxybenzoic acid(4), N-trans-cinnamic acid acyl-p-hydroxybenzene ethylamine(5),(+)-(1R,2S,3R,4S,5R,6S,9R)-2,11,12-trihydroxypicrotoxane-3(15)-lactone(6), dendronobilin H(7), soltorvum E(8). Compound 1 was a novel compound, named as soltorvum F. Compound 8 was isolated from Dendrobium species for the first time.

Species divergence and phylogeography of Corylus heterophylla Fisch complex (Betulaceae): Inferred from molecular, climatic and morphological data.

Historical geo-climatic changes have shaped the geographical distributions and genetic diversity of numerous plant taxa in East Asia, which promote species divergence and ultimately speciation. Here, we integrated multiple approaches, including molecular phylogeography, ecological niche modeling, and morphological traits to examine the nucleotide diversity and interspecific divergence within Corylus heterophylla complex (C. heterophylla, C. kweichowensis, and C. yunnanensis). These three sibling taxa harbored similar high levels of nucleotide diversity at the species level. The molecular data (SCNG and cpDNA) unanimously supported the division of C. heterophylla complex into two major clades, with C. yunnanensis diverged earlier from the complex, whereas C. heterophylla and C. kweichowensis could hardly be separated. The split between the two clades (c. 12.89 Ma) coincided with the formation of Sichuan Basin in the middle Miocene, while the divergence among and within the five subclades (YUN1-YUN3, HK1-HK2) occurred from the late Miocene to the Pleistocene. C. heterophylla of northern China experienced glacial contraction and interglacial expansion during the Quaternary, whereas C. kweichowensis and C. yunnanensis of southern China presented population expansion even during the last glacial maximum. Despite of high levels of genetic admixture between C. heterophylla and C. kweichowensis, significant ecological and morphological discrepancy as well as incomplete geographic isolation indicated that adaptive evolution triggered by divergent selection may have played important roles in incipient ecological speciation.

Identification of different proteins binding to Na, K-ATPase α1 in LPS-induced ARDS cell model by proteomic analysis.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is characterized by refractory hypoxemia caused by accumulation of pulmonary fluid, which is related to inflammatory cell infiltration, impaired tight junction of pulmonary epithelium and impaired Na, K-ATPase function, especially Na, K-ATPase α1 subunit. Up until now, the pathogenic mechanism at the level of protein during lipopolysaccharide- (LPS-) induced ARDS remains unclear. METHODS: Using an unbiased, discovery and quantitative proteomic approach, we discovered the differentially expressed proteins binding to Na, K-ATPase α1 between LPS-A549 cells and Control-A549 cells. These Na, K-ATPase α1 interacting proteins were screened by co-immunoprecipitation (Co-IP) technology. Among them, some of the differentially expressed proteins with significant performance were identified and quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Data are available via ProteomeXchange with identifier PXD032209. The protein interaction network was constructed by the related Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Several differentially expressed proteins were validated by Western blot. RESULTS: Of identified 1598 proteins, 89 were differentially expressed proteins between LPS-A549 cells and Control-A549 cells. Intriguingly, protein-protein interaction network showed that there were 244 significantly enriched co-expression among 60 proteins in the group control-A549. while the group LPS-A549 showed 43 significant enriched interactions among 29 proteins. The related GO and KEGG analysis found evident phenomena of ubiquitination and deubiquitination, as well as the pathways related to autophagy. Among proteins with rich abundance, there were several intriguing ones, including the deubiquitinase (OTUB1), the tight junction protein zonula occludens-1 (ZO-1), the scaffold protein in CUL4B-RING ubiquitin ligase (CRL4B) complexes (CUL4B) and the autophagy-related protein sequestosome-1 (SQSTM1). CONCLUSIONS: In conclusion, our proteomic approach revealed targets related to the occurrence and development of ARDS, being the first study to investigate significant differences in Na, K-ATPase α1 interacting proteins between LPS-induced ARDS cell model and control-A549 cell. These proteins may help the clinical diagnosis and facilitate the personalized treatment of ARDS.

Diagnostic utility of pleural cell-free nucleic acids in undiagnosed pleural effusions.

Pleural effusion (PE) is a common sign caused by various disorders. Microbiology, histology and cytology are reference standards for these disorders. However, these diagnostic tools have limitations, including invasiveness, high cost, long turnaround time, and observer-dependent. Soluble biomarkers in pleural fluid (PF) are promising diagnostic tools because they are mininvasive, economical, and objective. Recent studies have revealed that some cell-free nucleic acids (e.g., DNA, mRNA, microRNA, and lncRNA) in PF are potential diagnostic markers for many disorders. Here, we review the performance of PF cell-free nucleic acids for differentiating and stratification of PE.

Exploring the Use of the Current Perception Threshold in Pharyngeal Paresthesia Patients.

To explore pharyngeal sensory function by current perception threshold (CPT) measurement in paresthetic pharynx. In total, 58 healthy participants and 66 patients with pharyngeal paresthetic symptoms underwent CPT evaluation. Pharyngeal paresthesia (n = 66) was classified into three categories based on aetiologies: six cases with pain in pharynx; 34 neuropathic patients with glossopharyngeal nerve and/or vagus nerve or recurrent laryngeal nerve injury; and 26 patients with globus pharyngeus. CPT measurements were obtained from bilateral palatoglossal arch and tongue base at 2000, 250 and 5 Hz stimulation frequencies. Ranked from high to low, the CPT values for the bilateral palatoglossal arches and tongue bases were: lower cranial neuropathic patients, globus pharyngeus, healthy participants and patients with pain. The CPT values for neuropathic patients on the injured side were significantly higher than those on the healthy side (P < 0.05). The CPT values for patients with pain in pharynx were significantly lower than those of healthy participants (P < 0.05) when the bilateral tongue bases were stimulated. The CPT measurement is a reliable method for quantitatively assessing pharyngeal sensory function and able to differentiate pharyngeal paresthesia between lower cranial neuropathic and subjective discomfort. Pharyngeal sensory function is more sensitive in patients with pain in pharynx. Pharyngeal sensory function is significantly reduced in lower cranial neuropathic patients, especially on the injured side. Patients with globus pharyngeus have pharyngeal hyposensitivity.

Targeting translation regulators improves cancer therapy.

Deregulation of protein synthesis may be involved in multiple aspects of cancer, such as gene expression, signal transduction and drive specific cell biological responses, resulting in promoting cancer growth, invasion and metastasis. Study the molecular mechanisms about translational control may help us to find more effective anti-cancer drugs and develop novel therapeutic opportunities. Recently, the researchers had focused on targeting translational machinery to overcome cancer, and various small molecular inhibitors targeting translation factors or pathways have been tested in clinical trials and exhibited improving outcomes in several cancer types. There is no doubt that an insight into the class of translation regulation protein would provide new target for pharmacologic intervention and further provide opportunities to develop novel anti-tumor therapeutic interventions. In this review, we summarized the developments of translational control in cancer survival and progression et al, and highlighted the therapeutic approach targeted translation regulation to overcome the cancer.

Angelica sinensis Polysaccharide and Astragalus membranaceus Polysaccharide Accelerate Liver Regeneration by Enhanced Glycolysis via Activation of JAK2/STAT3/HK2 Pathway.

The promotion of liver regeneration is crucial to avoid liver failure after hepatectomy. Angelica sinensis polysaccharide (ASP) and Astragalus membranaceus polysaccharide (AMP) have been identified as being associated with hepatoprotective effects. However, their roles and specific mechanisms in liver regeneration remain to be elucidated. In the present study, it suggested that the respective use of ASP or AMP strikingly promoted hepatocyte proliferation in vitro with a wide range of concentrations (from 12.5 µg/mL to 3200 µg/mL), and a stronger promoting effect was observed in combined interventions. A significantly enhanced liver/body weight ratio (4.20%) on day 7 and reduced serum transaminase (ALT 243.53 IU/L and AST 423.74 IU/L) and total bilirubin (52.61 IU/L) levels on day 3 were achieved by means of ASP-AMP administration after partial hepatectomy in mice. Metabonomics showed that differential metabolites were enriched in glycolysis with high expression of beta-d-fructose 6-phosphate and lactate, followed by significantly strengthened lactate secretion in the supernatant (0.54) and serum (0.43) normalized to control. Upon ASP-AMP treatment, the knockdown of hexokinase 2 (HK2) or inhibited glycolysis caused by 2-deoxy-d-glucose decreased hepatocyte proliferation in vitro and in vivo. Furthermore, pathway analysis predicted the role of JAK2/STAT3 pathway in ASP-AMP-regulated liver regeneration, and phosphorylation of JAK2 and STAT3 was proven to be elevated in this promoting process. Finally, downregulated expression of HK2, an attenuated level of lactate secretion, and reduced hepatocyte proliferation were displayed when STAT3 was knocked out in vitro. Therefore, it can be concluded that ASP-AMP accelerated liver regeneration and exerted a hepatoprotective effect after hepatectomy, in which the JAK2/STAT3/HK2 pathway was actively involved in activating glycolysis.

Operationally defining physical literacy in Chinese culture: Results of a meta-narrative synthesis and the Panel's recommendations.

Purpose: The definition of physical literacy (PL) needs to be explored by researchers from educational, public health, and sports organisations in Chinese culture; an adequate definition and theoretical framework of PL can then be embraced within different contexts and according to cultural influences. Methods: This meta-narrative synthesis of literature in this area included a series of planning, search, mapping, appraisal, synthesis, and recommendation phases. The literature was translated into English and circulated among international experts to seek suggestions. A total of 74 articles were included in the PL definition synthesis and 28 were included for philosophical synthesis in this study. Results: Based on three rounds of discussions, the final agreement was reached among panel members regarding the defining statements and practical and theoretical models of PL in Chinese culture. According to consensus, PL is the integration of physical, perceptual, cognitive, psychological, and behavioural capabilities, echoing with the need for an active, healthy, and fulfilling lifestyle, which involves continuous positive interactions with the environment and embodied engagement in physical activities for life. The framework addressed five domains (physical, sensory-perceptual, cognitive, psychological, and behavioural) and one important overlapping factor (dynamic environment). A further explanation was provided in the defining statement to assist in understanding the concept. Conclusion: It is suggested that the cultural interpretation and historical background of PL in Chinese discourse should be addressed and respected. The development of a specific cultural definition statement of PL in one country could provide implications for PL researchers worldwide.

Non-targeted proteomics of acute respiratory distress syndrome: clinical and research applications.

Acute respiratory distress syndrome (ARDS) is characterized by refractory hypoxemia caused by accumulation of pulmonary fluid with a high mortality rate, but the underlying mechanism is not yet fully understood, causing absent specific therapeutic drugs to treat with ARDS. In recent years, more and more studies have applied proteomics to ARDS. Non-targeted studies of proteomics in ARDS are just beginning and have the potential to identify novel drug targets and key pathways in this disease. This paper will provide a brief review of the recent advances in the application of non-targeted proteomics to ARDS.

Silencing of the CrkL gene reverses the doxorubicin resistance of K562/ADR cells through regulating PI3K/Akt/MRP1 signaling.

BACKGROUND: Doxorubicin is a first-line chemotherapy agent on human myelogenous leukemia clinical treatment, but the development of chemoresistance has largely limited curative effect. In this study, we aimed to evaluate the biological function and molecular mechanisms of CrkL to Doxorubicin resistance. METHODS: Quantitative reverse transcription-PCR (qRT-PCR) assay was performed to examine the expression of CrkL in K562 and K562/ADR cells. The expression of CrkL was silenced through RNA interference technology. MTT assay and flow cytometry were performed to detect the proliferation inhibition and apoptosis rate after CrkL siRNA transfection. The protein expression changes of PI3K/AKT/MRP1 pathway induced by CrkL siRNA were observed by Western Blot assay. Xenograft tumor model was carried out to observe tumor growth in vivo. RESULTS: We observed that silencing of CrkL could effectively increase apoptosis rate induced by doxorubicin and dramatically reversed doxorubicin resistance in K562/ADR cells. Further studies revealed knockdown CrkL expression suppressed PI3K/Akt/MRP1 signaling, which indicated CrkL siRNA reversed doxorubicin effect through regulating PI3K/Akt/MRP1 pathway. In addition, overexpression of MRP1 could evidently reduce apoptosis rate and reversed the inhibitory effects of doxorubicin resistance caused by CrkL siRNA on K562/ADR cells. Finally, in vivo experiments revealed that CrkL silencing acted a tumor-suppressing role in myelogenous leukemia via regulating PI3K/Akt/MRP1 signaling. CONCLUSION: Together, we indicated that CrkL is up-regulated in myelogenous leukemia cells and silencing of CrkL could reverse Doxorubicin resistance effectively. These results show a potential novel strategy for intervention chemoresistance in myelogenous leukemia during chemotherapy.

Clinicopathological features and risk factors analysis of lymph node metastasis and long-term prognosis in patients with synchronous multiple gastric cancer.

BACKGROUND: As a common malignancy, gastric cancer (GC) remains an important threat to human's health. The incidence of synchronous multiple gastric cancer (SMGC) has increased obviously with technical advances of endoscopic and pathological examinations. Several studies have investigated the relationship between SMGC and solitary gastric cancer (SGC). However, little is known about the relationship between early and advanced SMGCs, and the independent risk factors of lymph node metastasis and prognosis in SMGC patients remain unclear. METHODS: We retrospectively collected 57 patients diagnosed as SMGC and underwent radical gastrectomies from December 2011 to September 2019. Epidemiological data and clinicopathological characteristics of all patients were recorded. Postoperative follow-up was performed by telephone or outpatient service. Chi-squared test or Fisher's exact test was adopted in analysis of categorical data. Continuous data were analyzed by using unpaired t test. Univariate and multivariate analyses were performed to investigate the independent risk factors of lymph node metastasis and tumor recurrence of SMGC. RESULTS: There were 45 males and 12 females. The average age was 62.1 years old. There were 20 patients with early SMGC and 37 patients with advanced SMGC. Most of patients (91.2%) had two malignant lesions. Tumor recurrence occurred in 8 patients, among which 7 patients died from recurrence. The rates of total gastrectomy, tumor size ≥ 2 cm, poorly differentiated type, lymph node metastasis, ulcer and nerve invasion, and preoperative CEA level were significantly higher in advanced SMGC patients compared to those with early SMGC. Lymphovascular cancer plug and preoperative CA125 were the independent risk factors of lymph node metastasis in patients with SMGC. Lymph node metastasis, nerve invasion, and preoperative AFP might be the risk factors of tumor recurrence of SMGC, but need further validation. CONCLUSIONS: In patients with SMGC, the presence of tumor size ≥ 2 cm, poorly differentiated type, lymph node metastasis, ulcer, nerve invasion, and relatively high preoperative CEA level might indicate the advanced SMGC. More attention should be paid to lymph node metastasis in SMGC patients with lymphovascular cancer plug and high preoperative CA125. Lymph node metastasis, nerve invasion, and preoperative AFP might be associated with recurrence of SMGC, needing further validation.

Effect of an 8-week Exercise Training on Gut Microbiota in Physically Inactive Older Women.

Exercise can alter the composition of gut microbiota. However, studies examining the effects of exercise on gut microbiota in the elderly are lacking. This study aims to investigate whether an 8-week exercise training affect gut microbiota in physically inactive elderly women. Fourteen women were randomly assigned to either exercise group or control group. Repeated-measures analysis of variance was used to reveal changes in gut microbiota. Alpha diversity did not change significantly. A tendency to form 2 clusters was observed for operational taxonomic units (OTU) after intervention. At phylum, class, and order levels, a significant difference was observed between two groups for Fusobacteria (F=5.257, P=0.045), Betaproteobacteria (F=5.149, P=0.047), and Bifidobacteriales (F=7.624, P=0.020). A significant interaction was observed between two groups for Actinobacteria (F=8.434, P=0.016). At family and genus levels, a significant main effect of groups was observed in Bifidobacteriaceae (F=7.624, P=0.020), Bifidobacterium (F=7.404, P=0.022), and Gemmiger (F=5.881, P=0.036). These findings indicate that an 8-week exercise training may induce partial changes in relative abundance and OTU clustering of gut microbiota in physically inactive elderly women. Also, exercise may increase the abundance of bacteria associated with anti-inflammation such as Verrucomicrobia, reduce the abundance of bacteria associated with pro-inflammation such as Proteobacteria.

Activation of muscarinic acetylcholine receptor 1 promotes invasion of hepatocellular carcinoma by inducing epithelial-mesenchymal transition.

Hepatocellular carcinoma is the second leading cause of cancer-related death worldwide. Neural regulation plays an important role in the development of hepatocellular carcinoma, and activation of sympathetic nervous system can promote the migration and invasion of cancer cells. However, little research has been conducted on how the vagus nerve influences hepatocellular carcinoma. In this study, we found that the expression of vesicular acetylcholine transporter, a biomarker of vagus nerve, was associated with hepatocellular carcinoma patients' clinicopathological characteristics by immunohistochemistry. Further, activation of muscarinic acetylcholine receptor 1 (M1R) promoted HepG2 and SMMC-7721 cells migration and invasion and epithelial-mesenchymal transition via PI3K/Akt pathway. Moreover, inhibition of M1R by antagonist or shRNA suppressed hepatocellular carcinoma cells migration and invasion in vitro and in vivo, inhibited epithelial-mesenchymal transition and PI3K/Akt pathway. Therefore, these results indicate that activation of M1R promotes invasion of hepatocellular carcinoma through epithelial-mesenchymal transition and PI3K/Akt pathway.

Comparison on the Efficacy of Double Tract Gastric Interposition Reconstruction Versus Jejunal Interposition Reconstruction After Proximal Gastrectomy.

BACKGROUND This study aimed to compare the efficacy of antrum-preserving double tract gastric interposition reconstruction (ADGR) versus antrum-preserving double tract jejunal interposition reconstruction (ADJR) after proximal gastrectomy (PG). MATERIAL AND METHODS In a retrospective study, 62 cases of proximal gastric cancer undergoing proximal gastrectomy were divided into an ADJR group (n=32) and an ADGR group (n=30) according to reconstruction methods. Perioperative outcomes and postoperative complications were compared between the 2 groups, and the changes in hemoglobin (Hb), total protein (TP), body weight, and quality of life (QOL) were observed at 1, 3, 6, and 12 months postoperatively. Endoscopy was given at 12 months postoperatively for assessing reflux esophagitis and residual food. RESULTS Differences were indistinct in the 2 groups regarding the operation time, intraoperative blood loss, postoperative length of stay (LOS), first flatus time, and postoperative complications (P>0.05). At 1, 3, 6, and 12 months after operation, no evident differences were shown between the 2 groups regarding weight loss and Visick scores (P>0.05). Compared with the ADJR group, the Hb level at 6 and 12 months after operation and TP level at 12 months after operation were increased markedly in the ADGR group (P<0.05). No apparent difference was detected between the 2 groups in reflux esophagitis (P=0.467). The incidence of residual food in the ADGR group was significantly lower than that in the ADJR group (6.67% versus 31.25%, P=0.014). CONCLUSIONS ADGR was superior to ADJR in improving nutritional status and preventing residual food of patients with proximal gastric cancer after proximal gastrectomy.

Biological conservation law as an emerging functionality in dynamical neuronal networks.

Scientists strive to understand how functionalities, such as conservation laws, emerge in complex systems. Living complex systems in particular create high-ordered functionalities by pairing up low-ordered complementary processes, e.g., one process to build and the other to correct. We propose a network mechanism that demonstrates how collective statistical laws can emerge at a macro (i.e., whole-network) level even when they do not exist at a unit (i.e., network-node) level. Drawing inspiration from neuroscience, we model a highly stylized dynamical neuronal network in which neurons fire either randomly or in response to the firing of neighboring neurons. A synapse connecting two neighboring neurons strengthens when both of these neurons are excited and weakens otherwise. We demonstrate that during this interplay between the synaptic and neuronal dynamics, when the network is near a critical point, both recurrent spontaneous and stimulated phase transitions enable the phase-dependent processes to replace each other and spontaneously generate a statistical conservation law-the conservation of synaptic strength. This conservation law is an emerging functionality selected by evolution and is thus a form of biological self-organized criticality in which the key dynamical modes are collective.