Functional Investigation and Two-sample Mendelian Randomization Study of Inguinal Hernia Hub Genes Obtained by Bioinformatics Analysis.

BACKGROUND: Inguinal hernia in adults is a common and frequent disease in surgery, prone to occur in the elderly or in those with a weak abdominal wall. Despite its prevalence, Molecular mechanisms underlying inguinal hernia formation are unclear. OBJECTIVE: This study aims to identify potential gene markers for inguinal hernia and available drugs. METHODS: Pubmed2Ensembl text mining was used to identify genes related to "inguinal hernia" keywords. The GeneCodis system was used to specify GO biological process terms and KEGG pathways defined in the Kyoto Encyclopedia of Genes and Genomes (KEGG). The STRING tool was used to construct protein-protein interaction networks, which were then visualized using Cytoscape.CytoHubba and Molecular Complex Detection were utilized to analyze the module (MCODE). A GO and KEGG analysis of gene modules was conducted using the DAVID platform database. Hub genes are those that are concentrated in prominent modules. The druggene interaction database was also used to identify potential drugs for inguinal hernia patients based on their interactions between the hub genes. Finally, a Mendelian randomization study was conducted based on genome-wide association studies to determine whether hub genes cause inguinal hernias. RESULTS: The identification of 96 genes associated with inguinal hernia was carried out using text mining techniques. It was constructed using PPI networks with 80 nodes and 476 edges, and the sequence of the genes was performed using CytoHubba. MCODE analysis identified three gene modules. Three modules contain 37 genes clustered as hub candidate genes associated with inguinal hernia patients. The PI3K-Akt, MAPK, AGE-RAGE, and HIF-1 pathways were found to be enriched in signaling pathways. Sixteen of the 37 genes were found to be targetable by 30 existing drugs. The relationship between hub genes and inguinal hernia was examined using Mendelian randomization. The research revealed nine genes that may be connected with inguinal hernia, such as POMC, CD40LG, TFRC, VWF, LOX, IGF2, BRCA1, TNF, and HGF in the plasma. By inverse variance weighting, ALB was associated with an increased risk of inguinal hernia with an OR of 1.203 (OR [95%] = 1,04 [1.012 to 1.089], p = 0.008). CONCLUSION: We identified potential hub genes for inguinal hernia, predicted potential drugs for inguinal hernia, and reverse-validated potential genes by Mendelian randomization. This may provide further insights into asymptomatic pre-diagnostic methods and contribute to studies to understand the molecular mechanisms of risk genes associated with inguinal hernia.

Spatial distribution, source identification, and transportation paths of plutonium in the Beibu Gulf, South China Sea.

To investigate the spatial distribution and source of plutonium isotopes in the Beibu Gulf, surface sediments were collected and analyzed using sector field inductively coupled plasma mass spectrometry (SF-ICP-MS). The activities of 239+240Pu in surface sediments ranged from 0.012 to 0.451 mBq/g (mean: 0.171 ± 0.138 mBq/g, n = 36), indicating a decreasing trend in a counterclockwise direction from the southern bay mouth. The counterclockwise decreasing trend in the south of the bay mouth is similar to the current in the Beibu Gulf. The 240Pu/239Pu atom ratios in surface sediments ranged from 0.156 to 0.283 (mean: 0.236 ± 0.031, n = 36), slightly higher than that of the global fallout value of 0.18. This suggests that the Pu in the Beibu Gulf was a combination of global fallout and Pacific Proving Ground (PPG). The average contribution of the plutonium (Pu) derived from the PPG in the sediment was estimated to be 52 % ± 24 %.

Exploring the application value of the modified Delphi method in the development process of acupuncture and moxibustion guideline recommendations based on the WFAS Clinical Practice Guideline for Female Urinary Incontinence. / 基于制定WFASã€Šå¥³æ€§å°¿å¤±ç¦ä¸´åºŠå®žè·µæŒ‡å—ã€‹æŽ¢è®¨æ”¹è‰¯å¾·å°”è²æ³•åœ¨é’ˆç¸æŒ‡å—æŽ¨èæ„è§ç ”åˆ¶è¿‡ç¨‹ä¸­çš„åº”ç”¨ä»·å€¼.

Taking the recommendations development of the World Federation of Acupuncture-Moxibustion Societies (WFAS) standard Clinical Practice Guideline for Female Urinary Incontinence as an example, this study analyzed the consensus expert composition, specific consensus process, and results in the development of the guideline's recommendations. It systematically examined the advantages of using the modified Delphi method in the formation of recommendations for acupuncture and moxibustion clinical practice guideline, with the aim of providing reference for the development of acupuncture and moxibustion guidelines in the same field.

A closed translocation channel in the substrate-free AAA+ ClpXP protease diminishes rogue degradation.

AAA+ proteases degrade intracellular proteins in a highly specific manner. E. coli ClpXP, for example, relies on a C-terminal ssrA tag or other terminal degron sequences to recognize proteins, which are then unfolded by ClpX and subsequently translocated through its axial channel and into the degradation chamber of ClpP for proteolysis. Prior cryo-EM structures reveal that the ssrA tag initially binds to a ClpX conformation in which the axial channel is closed by a pore-2 loop. Here, we show that substrate-free ClpXP has a nearly identical closed-channel conformation. We destabilize this closed-channel conformation by deleting residues from the ClpX pore-2 loop. Strikingly, open-channel ClpXP variants degrade non-native proteins lacking degrons faster than the parental enzymes in vitro but degraded GFP-ssrA more slowly. When expressed in E. coli, these open channel variants behave similarly to the wild-type enzyme in assays of filamentation and phage-Mu plating but resulted in reduced growth phenotypes at elevated temperatures or when cells were exposed to sub-lethal antibiotic concentrations. Thus, channel closure is an important determinant of ClpXP degradation specificity.

Monoclonal antibody targeting mu-opioid receptor attenuates morphine tolerance via enhancing morphine-induced receptor endocytosis.

Morphine is a frequently used analgesic that activates the mu-opioid receptor (MOR), which has prominent side effects of tolerance. Although the inefficiency of morphine in inducing the endocytosis of MOR underlies the development of morphine tolerance, currently, there is no effective therapy to treat morphine tolerance. In the current study, we aimed to develop a monoclonal antibody (mAb) precisely targeting MOR and to determine its therapeutic efficacy on morphine tolerance and the underlying molecular mechanisms. We successfully prepared a mAb targeting MOR, named 3A5C7, by hybridoma technique using a strategy of deoxyribonucleic acid immunization combined with cell immunization, and identified it as an immunoglobulin G mAb with high specificity and affinity for MOR and binding ability to antigens with spatial conformation. Treatment of two cell lines, HEK293T and SH-SY5Y, with 3A5C7 enhanced morphine-induced MOR endocytosis via a G protein-coupled receptor kinase 2 (GRK2)/ß-arrestin2-dependent mechanism, as demonstrated by immunofluorescence staining, flow cytometry, Western blotting, coimmunoprecipitation, and small interfering ribonucleic acid (siRNA)-based knockdown. This mAb also allowed MOR recycling from cytoplasm to plasma membrane and attenuated morphine-induced phosphorylation of MOR. We established an in vitro morphine tolerance model using differentiated SH-SY5Y cells induced by retinoic acid. Western blot, enzyme-linked immunosorbent assays, and siRNA-based knockdown revealed that 3A5C7 mAb diminished hyperactivation of adenylate cyclase, the in vitro biomarker of morphine tolerance, via the GRK2/ß-arrestin2 pathway. Furthermore, in vivo hotplate test demonstrated that chronic intrathecal administration of 3A5C7 significantly alleviated morphine tolerance in mice, and withdrawal jumping test revealed that both chronic and acute 3A5C7 intrathecal administration attenuated morphine dependence. Finally, intrathecal electroporation of silencing short hairpin RNA illustrated that the in vivo anti-tolerance and anti-dependence efficacy of 3A5C7 was mediated by enhanced morphine-induced MOR endocytosis via GRK2/ß-arrestin2 pathway. Collectively, our study provided a therapeutic mAb, 3A5C7, targeting MOR to treat morphine tolerance, mediated by enhancing morphine-induced MOR endocytosis. The mAb 3A5C7 demonstrates promising translational value to treat clinical morphine tolerance.

FAM46C-mediated tumor heterogeneity predicts extramedullary metastasis and poorer survival in multiple myeloma.

Cancers originate from a single cell according to Nowell's theory of clonal evolution. The enrichment of the most aggressive clones has been developed and the heterogeneity arises for genomic instability and environmental selection. Multiple myeloma (MM) is a multiple relapse plasma cell cancer generated from bone marrow. Although there were accumulating researches in multiple myeloma pathogenesis, the heterogeneity remains poorly understood. The participants enrolled in this study were 4 EMP+ (EMP, Extramedullary plasmacytoma) and 2 EMP- primarily untreated MM patients. Single cell RNA sequencing and analysis were conducted for the single cell suspension, which was sorted by flow cytometry from peripheral blood mononuclear cells or bone marrow cells. In our research, the results of single cell RNA sequencing show that FAM46C determines MM tumor heterogeneity predicting extramedullary metastasis by influencing RNA stability. Further, we integrated and analyzed 2280 multiple myeloma samples from 7 independent datasets, which uncover that FAM46C mediated tumor heterogeneity predicts poorer survival in multiple myeloma.

[Application of meridian and acupoint diagnosis of three yin meridians of foot in the treatment for gynecological diseases with acupuncture and moxibustion].

With three representative types of gynecological diseases (dysmenorrhea, pelvic inflammation, polycystic ovary syndrome) as examples, the application methods of meridian and acupoint diagnosis for gynecological diseases treated with acupuncture and moxibustion are discussed. During clinical diagnosis and treatment, it is recommended to examine the patient's leg segment along the three yin meridians of foot, aiming to explore the positive reactions of the meridians and acupoints (color, shape, skin temperature, sensory abnormalities, etc.). Acupuncture and moxibustion treatment at this positive reaction place can improve the clinical efficacy. Meridian and acupoint diagnosis could provide basis for meridian syndrome differentiation, thus guiding the selection of acupoint prescriptions; it is also helpful to clarify the deficiency, excess, cold and heat of the disease nature, thus guiding the selection of acupuncture and moxibustion methods. In addition, it is an auxiliary method to estimate the prognosis and outcome of the disease.

Irisin Attenuates Apoptosis Following Ischemia-Reperfusion Injury Through Improved Mitochondria Dynamics and ROS Suppression Mediated Through the PI3K/Akt/mTOR Axis.

Irisin is a muscle-derived hormone that promotes the survival of motor neurons and enhances muscle size following injury. In this study, we investigated the beneficial effects and mechanism(s) of action of irisin in response to cerebral ischemia-reperfusion injury (CIRI). Right-middle cerebral artery occlusion (MCAO) and hypoxia/reoxygenation (H/R) models were generated in C57BL/6 J mice. Mouse neuronal cell lines (NSC-34) were used to confirm the molecular mechanisms of the protection afforded by irisin in response to CIRI. We found that irisin (250 µg/kg) improved cerebral function and reduced the cerebral infarct volume following CIRI. Irisin also protected neuronal cells against ischemia-reperfusion (I/R) induced apoptosis, assessed via TUNEL, and cleaved Caspase-3 staining. Western blotting of neuronal tissue from irisin treated I/R mice showed lower expression of pro-apoptotic Bax and caspase-9 (P < 0.001 and P < 0.01) and increased levels of the pro-survival protein Bcl-2 (P < 0.01 & P < 0.001 vs. I/R). Irisin also reduced the levels of reactive oxygen species (ROS) characterized through malondialdehyde (MDA) assays. Irisin was found to maintain mitochondrial homeostasis through the suppression of mitochondrial fission-linked dynamin-related protein 1 in CIRI mice (P < 0.01 and P < 0.05 v. I/R cohort). Moreover, mitochondrial fusion-related protein (Mfn2) and Opa1 expression were rescued following irisin treatment (P < 0.001 and P < 0.01 v. I/R cohort). Cell-based assays showed that irisin activates PI3K/AKT/mTOR signaling in the neurons of CIRI mice. Furthermore, the beneficial effects of irisin on NSC-34 cell-survival, mitochondrial function, and ROS generation were reversed by VS-5584, a highly specific PI3K/AKT/mTOR inhibitor. Collectively, these data highlight the ability of irisin to alleviate CIRI in vivo and in vitro. The mechanisms of action of irisin include the attenuation of apoptosis through the prevention of mitochondrial fission and increased mitochondrial fusion and the alleviation of oxidative stress through activation of the PI3K/AKT/mTOR axis. We therefore identify irisin as a much-needed therapeutic for CIRI.

Inactivation of horseradish peroxidase with crotonic acid for reprobing of western blotting.

Inactivation of horseradish peroxidase (HRP) treatment is a conventional preference to stripping for sequential detections of different proteins of chemiluminescent western blotting (WB). However, little evidence exists on whether other chemical substances treatment can affects the biological activity of HRP during stripping and re-probing of WB blots. Here, we successfully develop 20% crotonic acid (CA) as an alternative to stripping to inhibit HRP used for sequential chemiluminescent WB on polyvinylidene difluoride (PVDF) and Nitrocellulose (NC) membrane. Moreover, NC blots incubation in CA (40 °C, 30min) allow us to perform three round HRP inhibition in sequential detections without losing transferred proteins and damaging membrane. Hence, the method will help us save time and valuable samples without the need to rerun gels.

Clinical features and prognosis of multiple myeloma and orbital extramedullary disease: Seven cases report and review of literature.

BACKGROUND: Multiple myeloma (MM) complicated with extramedullary disease (EMD) has a poor prognosis and is a limiting factor in the treatment of MM, and no standard treatment is recommended in international guidelines. Few studies have reported MM with periorbital EMD. CASE SUMMARY: In this paper, the clinical characteristics and survival of seven patients with multiple myeloma and orbital are described and analyzed. The common ocular symptoms were blurred vision, proptosis and/or eye movement disorders, IgG type MM may be a risk factor for orbital involvement. Of them, six patients were treated with bortezomib-based regimens. The median overall survival (OS) and progression free survival for the entire cohort were 48 and 33 mo, respectively, which was much worse than the OS reported for MM patients without orbital EMD. CONCLUSION: Orbital MM may have significantly shortened survival for the entire cohort, so multidisciplinary collaboration is emphasized and recommended in the diagnosis and treatment of these difficult cases.

Role of CC-chemokine ligand 2 in gynecological cancer.

Gynecological cancer is one of the most severe diseases that threaten the lives and health of women worldwide. Its incidence rate increases with each passing year and becomes more prevalent among young people. The prognosis of gynecological cancer remains poor despite significant advances in surgical removal and systemic chemotherapy. Several chemokines play a role in the progression of gynecologic cancers. CCL2 (CC-chemokine ligand 2), also termed MCP-1 (monocyte chemotactic protein 1), plays a significant physiological role in monocyte cell migration and the inflammatory response. Recent studies have demonstrated that CCL2 plays a pro-tumorigenic function in the tumor microenvironment. According to previous studies, CCL2 plays a significant role in the occurrence and development of gynecological cancers. Furthermore, recent studies noted that CCL2 could be a potential diagnostic biomarker and prognostic predictor. The purpose of this paper is to review the role of CCL2 in the occurrence and development of gynecological cancers and to discuss the potential therapeutic strategy of CCL2 for gynecological cancers, with a primary focus on breast cancer, ovarian cancer, cervical cancer, and endometrial cancer.

Mechanism of opioid addiction and its intervention therapy: Focusing on the reward circuitry and mu-opioid receptor.

Opioid abuse and addiction have become a global pandemic, posing tremendous health and social burdens. The rewarding effects and the occurrence of withdrawal symptoms are the two mainstays of opioid addiction. Mu-opioid receptors (MORs), a member of opioid receptors, play important roles in opioid addiction, mediating both the rewarding effects of opioids and opioid withdrawal syndrome (OWS). The underlying mechanism of MOR-mediated opioid rewarding effects and withdrawal syndrome is of vital importance to understand the nature of opioid addiction and also provides theoretical basis for targeting MORs to treat drug addiction. In this review, we first briefly introduce the basic concepts of MORs, including their structure, distribution in the nervous system, endogenous ligands, and functional characteristics. We focused on the brain circuitry and molecular mechanism of MORs-mediated opioid reward and withdrawal. The neuroanatomical and functional elements of the neural circuitry of the reward system underlying opioid addiction were thoroughly discussed, and the roles of MOR within the reward circuitry were also elaborated. Furthermore, we interrogated the roles of MORs in OWS, along with the structural basis and molecular adaptions of MORs-mediated withdrawal syndrome. Finally, current treatment strategies for opioid addiction targeting MORs were also presented.

[Effects of Damming and Impoundment on Planktonic Microbial Community Structure and Interspecific Interaction Patterns in Different Water Depths].

Microbial communities play an important role in ecological processes through direct or indirect interactions. However, the interspecific interaction pattern of reservoir microorganisms has still received little attention. The Hengshan Reservoir in Jiangsu province was selected as the research area. Surface and deep water samples were collected to respectively explore the response of planktonic microbial community structure and the molecular ecological network to water depth changes, as well as to identify the key species of planktonic microbial communities in different water depths. The results showed that the richness and evenness of planktonic microorganisms in the surface layer were higher than those in the deep layer, and there were significant differences in the community structure of planktonic microorganisms in different depths. Water depth indirectly affected the planktonic microbial community by changing the environmental heterogeneity, among which the indicators such as TOC, NO3-, NH4+, and PO43- had the most significant impact on the planktonic microbial community structure. In addition, the number of nodes and edges of the deep planktonic microbial molecular ecological network were significantly higher than those on the surface, and the type and number of key species in the deep planktonic microbial community were significantly higher than those on the surface, indicating that the network scale of the deep planktonic microbial community was larger; however, the interspecific cooperative relationship and network connectivity of the surface planktonic microbial community were stronger. These results will provide a scientific basis for the study of interspecific interactions of reservoir microbial communities and are of great significance for predicting the ecological law of microorganisms in reservoir ecosystems and the impact of global material cycles.

Blockade of mIL-6R alleviated lipopolysaccharide-induced systemic inflammatory response syndrome by suppressing NF-κB-mediated Ccl2 expression and inflammasome activation.

Systemic inflammatory response syndrome (SIRS) is characterized by dysregulated cytokine release, immune responses and is associated with organ dysfunction. IL-6R blockade indicates promising therapeutic effects in cytokine release storm but still remains unknown in SIRS. To address the issue, we generated the human il-6r knock-in mice and a defined epitope murine anti-human membrane-bound IL-6R (mIL-6R) mAb named h-mIL-6R mAb. We found that the h-mIL-6R and the commercial IL-6R mAb Tocilizumab significantly improved the survival rate, reduced the levels of TNF-α, IL-6, IL-1ß, IFN-γ, transaminases and blood urea nitrogen of LPS-induced SIRS mice. Besides, the h-mIL-6R mAb could also dramatically reduce the levels of inflammatory cytokines in LPS-treated THP-1 cells in vitro. RNA-seq analysis indicated that the h-mIL-6R mAb could regulate LPS-induced activation of NF-κB/Ccl2 and NOD-like receptor signaling pathways. Furthermore, we found that the h-mIL-6R mAb could forwardly inhibit Ccl2 expression and NLRP3-mediated pyroptosis by suppressing NF-κB in combination with the NF-κB inhibitor. Collectively, mIL-6R mAbs suppressed NF-κB/Ccl2 signaling and inflammasome activation. IL-6R mAbs are potential alternative therapeutics for suppressing excessive cytokine release, over-activated inflammatory responses and alleviating organ injuries in SIRS.

Serotonergic Neurons in the Brain and Gnathal Ganglion of Larval Spodoptera frugiperda.

The fall armyworm Spodoptera frugiperda (S. frugiperda) (Lepidoptera: Noctuidae) is a worldwide, disruptive, agricultural pest species. The larvae of S. frugiperda feed on seedling, leave, and kernel of crops with chewing mouthparts, resulting in reduced crop yields. Serotonin is an important biogenic amine acting as a neural circuit modulator known to mediate lots of behaviors including feeding in insects. In order to explore the serotonergic neural network in the nervous system of larval S. frugiperda, we performed immunohistochemical experiments to examine the neuropil structure of the brain and the gnathal ganglion with antisynapsin and to examine their serotonergic neurons with antiserotonin serum. Our data show that the brain of larval S. frugiperda contains three neuromeres: the tritocerebrum, the deutocerebrum, and the protocerebrum. The gnathal ganglion also contains three neuromeres: the mandibular neuromere, the maxillary neuromere, and the labial neuromere. There are about 40 serotonergic neurons in the brain and about 24 serotonergic neurons in the gnathal ganglion. Most of these neurons are wide-field neurons giving off processes in several neuropils of the brain and the gnathal ganglion. Serotonergic neuron processes are mainly present in the protocerebrum. A pair of serotonergic neurons associated with the deutocerebrum has arborizations in the contralateral antennal lobe and bilateral superior lateral protocerebra. In the gnathal ganglion, the serotonergic neuron processes are also widespread throughout the neuropil and some process projections extend to the tritocerebrum. These findings on the serotonergic neuron network in larval S. frugiperda allow us to explore the important roles of serotonin in feeding and find a potential approach to modulate the feeding behavior of the gluttonous pest and reduce its damage.

Effect of Acupoint Catgut Embedding for Middle-Aged Obesity: A Multicentre, Randomised, Sham-Controlled Trial.

Objectives: This study aimed to examine the efficacy and safety of acupoint catgut embedding (ACE) for obesity over a 16-week treatment period using sham stimulation as the control. Methods: A multicenter, randomised, parallel, sham-controlled trial was conducted from February 10, 2017, to May 15, 2018. Men with waistlines ≥85 cm and women with ≥80 cm at three sites were randomised to receive eight sessions (over 16 weeks) of ACE (n = 108) or sham ACE (n = 108) with skin penetration at sham acupoints. The catgut was embedded once every two weeks using two alternating sets of acupoints. The follow-up lasted for an additional 24 weeks. The primary outcome was the percentage waistline reduction from baseline to week 16. Results: We included 216 individuals in the intention-to-treat analysis. At 16 weeks, the rate of waistline reduction was 8.80% (95% confidence interval (CI), 7.93% to 9.66%) in the ACE group and 4.09% (95% CI, 3.18% to 5.00%) in the sham control group, with a between-group difference of 4.71% (95% CI, 3.47% to 5.95%; P < 0.0001). This difference persisted throughout the entire follow-up period (between-group difference after 24-week additional weeks, 4.94% (95% CI, 3.58% to 6.30%); P < 0.001). The subgroup analyses of waistline by sex (male/female) revealed treatment effects of 1.93 (95% CI, -0.37 to 4.23, P = 0.1) in the male group and 3.19 (95% CI, 1.99 to 4.39, P < 0.001) in the female group. The adverse event analysis suggested that ACE and laboratory tests confirmed the safety of ACE. Discussion. ACE for 16 weeks could decrease the waistline and weight and was safe for the treatment of obesity. Further research is needed to evaluate the long-term efficacy and sex differences. This trial is registered with NCT02936973.

A four oxidative stress gene prognostic model and integrated immunity-analysis in pancreatic adenocarcinoma.

Background and aims: Pancreatic adenocarcinoma (PAAD) is highly aggressive and characterized by a poor prognosis. Oxidative stress has great impacts on the occurrence and development of tumors. However, the predictive role of oxidative stress related genes on PAAD patients' prognosis remains unclear. In this study, we aimed to construct a prognostic model for PAAD based on oxidative stress genes and to evaluate its predictive value. Methods: The Cancer Genome Atlas (TCGA) and three Gene Expression Omnibus (GEO) datasets were used to identify differentially expressed oxidative stress genes. Univariate Cox regression, Kaplan-Meier and multivariate Cox regression analysis were used to select genes and to construct a prognosis model. According to the median value of the model's risk score, patients were divided into high and low risk groups, and gene set enrichment analysis (GSEA), immune infiltration and immunotherapy effect, drug resistance and the expression of immune checkpoint related genes and synthetic driver genes of T cell proliferation were analyzed. Finally, the mRNA and protein levels of four genes in PAAD were verified by the clinical proteomic tumor analysis consortium (CPTAC) database and the immunostaining of patients' tissue. Results: 55 differentially expressed oxidative stress genes were identified, and four genes including MET, FYN, CTTN and CDK1 were selected to construct a prognosis model. GESA indicated that immune related pathways, metabolic pathways and DNA repair pathways were significantly enriched in the high risk group as compared to the low risk group. The frequency of genetic mutations was also significantly higher in high risk groups than that in low risk groups. Moreover, the infiltration level of 23 immune cells as well as the expression of immune checkpoint related and synthetic driver genes of T cell proliferation were significantly altered, with the better immunotherapy effect occurring in low risk group. In patient PAAD tissues, the mRNA and protein levels of these four genes were up-regulated. Conclusion: We have successfully constructed a four oxidative stress gene prognostic model that has important predictive value for PAAD patients, and this model might be a promising guidance for prognostic prediction and efficacy monitoring in clinical individualized therapy.

Total protein staining with Congo red as an alternative loading control for western blot analysis.

For western blot analysis, a housekeeping protein, such as ß-actin or glyceraldehyde-3-phosphate dehydrogenase, is used as loading control with the assumption that these proteins are stable. In practice, these internal loading control proteins vary with different cell states and tissue types. These internal standards are not appropriate for use with serum, extracellular secretion, cerebrospinal fluid analysis or for protein purification. We investigated total protein measurement using Congo red staining and found it to be a superior alternative to routine loading controls. Advantages include lower cost, technical simplicity and improved linear regression. We propose using Congo red staining for total protein immunoblotting to evaluate protein loading in western blots.

Examining failure learning in online lending: Complete failure vs. incomplete failure.

We examine the learning effects of borrowers' failures in online lending. Based on funding ratios of borrowers' loan listings in online lending, we first explore the role of failure degree in borrowers' future funding performance. Further, we disaggregate borrowers' funding failure into complete failure and incomplete failure, and compare theirs learning effects. Using a large sample of 610,000 online loan applications over six years from a Chinese leading online lending platform Renrendai, we use funding ratio to quantifiably measure each loan listing's failure degree and conduct a series of tests. The results show that: (1) Borrowers' failure degree of prior loan applications is negatively associated with one's subsequent funding performance. (2) Borrowers' complete failure cannot promote learning, while incomplete failure is good for future performance. (3) Both incomplete failure and complete failure interacted to influence the value of each type of experience and generate improved learning. Our results are robust across a variety of settings. The study sheds light for deeply understanding of failure learning phenomenon, and can also provide important implications for online lending managers to support successful financial transactions.

Exosomal microRNA-15a from mesenchymal stem cells impedes hepatocellular carcinoma progression via downregulation of SALL4.

Hepatocellular carcinoma (HCC) is a heterogeneous tumor with an increased incidence worldwide accompanied by high mortality and dismal prognosis. Emerging evidence indicates that mesenchymal stem cells (MSCs)-derived exosomes possess protective effects against various human diseases by transporting microRNAs (miRNAs or miRs). We aimed to explore the role of exosomal miR-15a derived from MSCs and its related mechanisms in HCC. Exosomes were isolated from transduced MSCs and co-incubated with Hep3B and Huh7 cells. miR-15a expression was examined by RT-qPCR in HCC cells, MSCs, and secreted exosomes. CCK-8, transwell, and flow cytometry were used to detect the effects of miR-15a or spalt-like transcription factor 4 (SALL4) on cell proliferative, migrating, invasive, and apoptotic properties. A dual-luciferase reporter gene assay was performed to validate the predicted targeting relationship of miR-15a with SALL4. Finally, in vivo experiments in nude mice were implemented to assess the impact of exosome-delivered miR-15a on HCC. The exosomes from MSCs restrained HCC cell proliferative, migrating, and invasive potentials, and accelerated their apoptosis. miR-15a was expressed at low levels in HCC cells and could bind to SALL4, thus curtailing the proliferative, migrating, and invasive abilities of HCC cells. Exosomes successfully delivered miR-15a to HCC cells. Exosomal miR-15a depressed tumorigenicity and metastasis of HCC tumors in vivo. Overall, exosomal miR-15a from MSCs can downregulate SALL4 expression and thereby retard HCC development.