The GABAergic pathway from anterior cingulate cortex to lateral hypothalamus area regulates irritable bowel syndrome in mice and its underlying mechanism.

Irritable bowel syndrome (IBS), which is characterized by chronic abdominal pain, has a high global prevalence. The anterior cingulate cortex (ACC), which is a pivotal region involved in pain processing, should be further investigated regarding its role in the regulation of visceral sensitivity and mental disorders. A C57BL/6J mouse model for IBS was established using chronic acute combining stress (CACS). IBS-like symptoms were assessed using behavioral tests, intestinal motility measurements, and abdominal withdrawal reflex scores. Fluoro-Gold retrograde tracing and immunohistochemistry techniques were employed to investigate the projection of ACC gamma-aminobutyric acid-producing (GABAergic) neurons to the lateral hypothalamus area (LHA). Chemogenetic approaches enabled the selective activation or inhibition of the ACC-LHA GABAergic pathway. Enzyme-linked immunosorbent assay (ELISA) and western blot analyses were conducted to determine the expression of histamine, 5-hydroxytryptamine (5-HT), and transient receptor potential vanilloid 4 (TRPV4). Our findings suggest that CACS induced IBS-like symptoms in mice. The GABA type A receptors (GABAAR) within LHA played a regulatory role in modulating IBS-like symptoms. The chemogenetic activation of ACC-LHA GABAergic neurons elicited anxiety-like behaviors, intestinal dysfunction, and visceral hypersensitivity in normal mice; however, these effects were effectively reversed by the administration of the GABAAR antagonist Bicuculline. Conversely, the chemogenetic inhibition of ACC-LHA GABAergic neurons alleviated anxiety-like behaviors, intestinal dysfunction, and visceral hypersensitivity in the mouse model for IBS. These results highlight the crucial involvement of the ACC-LHA GABAergic pathway in modulating anxiety-like behaviors, intestinal motility alterations, and visceral hypersensitivity, suggesting a potential therapeutic strategy for alleviating IBS-like symptoms.

Enhanced Herbicide Metabolism and Target Site Mutation Enabled the Multiple Resistance to Cyhalofop-butyl, Florpyrauxifen-benzyl, and Penoxsulam in Echinochloa crus-galli.

This study investigated the multiple herbicide resistance (MHR) mechanism of one Echinochloa crus-galli population that was resistant to florpyrauxifen-benzyl (FPB), cyhalofop-butyl (CHB), and penoxsulam (PEX). This population carried an Ala-122-Asn mutation in the acetolactate synthase (ALS) gene but no mutation in acetyl-CoA carboxylase (ACCase) and transport inhibitor response1 (TIR1) genes. The metabolism rate of PEX was 2-fold higher, and the production of florpyrauxifen-acid and cyhalofop-acid was lower in the resistant population. Malathion and 4-chloro-7-nitrobenzoxadiazole (NBD-Cl) could reverse the resistance, suggesting that cytochrome P450 (CYP450) and glutathione S-transferase (GST) contribute to the enhanced metabolism. According to RNA-seq and qRT-PCR validation, two CYP450 genes (CYP71C42 and CYP71D55), one GST gene (GSTT2), two glycosyltransferase genes (rhamnosyltransferase 1 and IAAGLU), and two ABC transporter genes (ABCG1 and ABCG25) were induced by CHB, FPB, and PEX in the resistant population. This study revealed that the target mutant and enhanced metabolism were involved in the MHR mechanism in E. crus-galli.

Regulation of the MCHergic Neural Circuit to Dorsal Raphe Nucleus on Emotion-Related Behaviors and Intestinal Dysfunction in Mice Model of Irritable Bowel Syndrome with Diarrhea.

INTRODUCTION: Irritable bowel syndrome with diarrhea (IBS-D) is frequently accompanied by depression and anxiety, resulting in a reduced quality of life and increased medical expenditures. Although psychological factors are known to play an important role in the genesis and development of IBS-D, an understanding of the central neural control of intestinal dysfunction remains elusive. Melanin-concentrating hormone (MCH) is a gut-brain peptide involved in regulating feeding, sleep-wake rhythms, and emotional states. METHODS: This study investigated the regulation of the MCHergic neural circuit from the lateral hypothalamic area (LHA) to the dorsal raphe nucleus (DRN) on anxiety- and depression-like behaviors, intestinal motility, and visceral hypersensitivity in a mice model of IBS-D. The models of IBS-D were prepared by inducing chronic unpredictable mild stress. RESULTS: Chemogenetic activation of the MCH neurons in the LHA could excite serotonin (5-HT) neurons in the DRN and induce anxiety- and depression-like behaviors and IBS-D-like symptoms, which could be recovered by microinjection of the MCH receptor antagonist SNAP94847 into the DRN. The mice model of IBS-D showed a reduction of 5-HT and brain-derived neurotrophic factor (BDNF) expression in the DRN, while an elevation of 5-HT and BDNF was observed in the colon through immunofluorescent staining, ELISA, and Western blot analysis. SNAP94847 treatment in the DRN alleviated anxiety- and depression-like behaviors, improved intestinal motility, and alleviated visceral hypersensitivity responses by normalizing the 5-HT and BDNF expression in the DRN and colon. CONCLUSION: This study suggests that the activation of MCH neurons in the LHA may induce IBS-D symptoms via the DRN and that the MCH receptor antagonist could potentially have therapeutic effects.

Roles of PD-L1 in human adipose-derived mesenchymal stem cells under inflammatory microenvironment.

Mesenchymal stem cells (MSCs) display unique homing and immunosuppression features which make them promising candidates for cell therapy in inflammatory disorders. It is known that C-X-C chemokine receptor type 4 (CXCR4, also known as CD184) is a critical receptor implicated in MSCs migration, and the protein programmed death ligand-1 (PD-L1) is involved in MSC's immunosuppression. However, it remains unclear how the molecular mechanisms regulate PD-L1 expression for migration and immunosuppression of MSCs under the inflammatory microenvironment. In this article, we used the human adipose-derived mesenchymal stem cells (hADMSCs) treated with lipopolysaccharide (LPS) as an in vitro inflammatory model to explore the roles of PD-L1 on the migration and immunosuppression of MSC. Our results demonstrate that in hADMSCs, LPS significantly increased PD-L1 expression, which mediated the migration of the LPS-treated hADMSCs via CXCR4. In addition, we found that the increased PD-L1 expression in the LPS-treated hADMSCs inhibited B cell proliferation and immunoglobulin G secretion through nuclear factor-κB. Our study suggests that the PD-L1 plays critical roles in the homing and immunosuppression of MSCs which are a promising cell therapy to treat inflammatory diseases.

Post-Emergence Water-Dispersal Application Provides Equal Herbicidal Activity against Echinochloa crus-galli and Rice Safety as Foliar Spraying of Penoxsulam.

Penoxsulam is an acetolactate synthase (ALS)-inhibiting herbicide usually applied by post-emergence foliar spraying (PFS) for the control of Echinochloa crus-galli and numerous annual weeds in paddy fields. Herbicides applied by foliar spraying can have negative impacts on the environment, ecosystems, and human health. In this study, the response of E. crus-galli and rice to the PFS and post-emergence water-dispersal (PWD) applications of penoxsulam, and the differences in the detoxification displayed by them between the two treatment methods were compared. The results showed that the PWD application of penoxsulam provides a similar control efficacy against E. crus-galli as PFS at the 1-, 3-, and 5-leaf stages. Meanwhile, the PWD application had a higher safety for the rice. After being treated with 30 g a.i. ha-1 penoxsulam, residues were not detected in the rice treated by the PWD application method, whereas, with the PFS treatment, there was 59.0 µg/kg penoxsulam remaining. With the PFS application, there were many more residues of penoxsulam in the E. crus-galli than with the PWD method; the amount of residues was 32-fold higher 12 h after treatment. The in vitro enzyme activity assays revealed that the activities of ALS, glutathione-S-transferase (GST), and cytochrome P450 monooxygenases (P450) were increased in the PWD treatments, and were 1.5-, 1.3-, and 2.3-fold higher than with PFS 72 h after treatment. The real-time quantitative PCR (qRT-PCR) revealed that the GST1 and P450 genes, CYP81A14, CYP81A12, CYP81A18, and CYP81A21 were upregulated with the PWD application versus PFS in the E. crus-galli. In summary, these results demonstrate that the herbicidal activity was not affected by the upregulation of target and metabolic enzyme activities with the PWD application of penoxsulam. This research could contribute to application strategies reducing the risk of rice injury and environmental impacts by using water-dispersal formulations of penoxsulam.

Association of environmental polycyclic aromatic hydrocarbons exposure with periodontitis in NHANES 2009-2014: A mixtures approach.

BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) can invade and cause harm to the human body through various pathways, but there is currently little research on the relationship between mixed-PAHs exposure and periodontitis. The purpose of this study was to examine the effects of mixed-urinary PAHs exposure on periodontitis in adults in the United States. METHODS: The cross-sectional study included 2749 subjects selected from the National Health and Nutrition Examination Survey (NHANES) 2009-2014 cycles. A professional examination of the periodontal status was conducted to distinguish between periodontitis and non-periodontitis based on the Centers for Disease Control and Prevention/American Academy of Periodontology (CDC/AAP) case definition. Laboratory testing of urine samples was performed to obtain the levels of urinary PAHs. Pearson correlation coefficients were utilized to determine the degree of correlation between urinary PAHs, while weighted binary logistic regression and Bayesian kernel machine regression (BKMR) were employed to evaluate the relationship between urinary PAHs and periodontitis. RESULTS: In a single-exposure model, 3-hydroxyfluorene (OH-3F), 2-hydroxyfluorene (OH-2F), 1-hydroxyphenanthrene (OH-1Ph), and 2-hydroxyphenanthrene and 3-hydroxyphenanthrene (OH-2,3Ph) were positively associated with periodontitis risk. In the mixed-exposure model, BKMR analysis demonstrated that mixed exposure to urinary PAHs was positively associated with periodontitis, with OH-2F being the most critical factor for the overall mixed effects (posterior inclusion probability [PIP] = 0.98). Univariate exposure-response function and univariate effects analysis revealed a positive correlation between urinary OH-2F levels and periodontitis. CONCLUSIONS: The study reveals a significant positive correlation between exposure to mixed PAHs and periodontitis, with a particular emphasis on the pivotal role of OH-2F. Mitigating PAHs in the environment may serve as a preventive measure against periodontitis and alleviate its global public health burden.

Target recognition initiated self-dissociation based DNA nanomachine for sensitive and accurate MicroRNA (miRNA) detection.

As a valuable biomarker for various tumor, sensitive and reliable quantitative determination of microRNA (miRNA) is crucial for both disease diagnosis and cancer treatment. Herein, we depict a novel simple and sensitive miRNA detection approach by exploiting an elegantly designed target recognition initiated self-dissociation based DNA nanomachine. In this nanomachine, target recognition assists the formation of active DNAzyme secondary conformation, and the active DNAzyme generates a nicking site in H probe, initiating the self-assembly of H probe. With the reflexed sequences as primer, dual signal recycles are formed under the cooperation of DNA polymerase and Nb.BbvCI. Eventually, the method exhibits a high sensitivity with the limit of detection as low as 12 fM. In addition, the method is also demonstrated with a high selectivity that can distinguish one mismatched base pair. We believe the established approach can be a robust tool for the early-diagnosis of a variety of cancers and also in anticancer drug development.

Expression and function analysis of crustacyanin gene family involved in resistance to heavy metal stress and body color formation in Exopalaemon carinicauda.

Crustacyanin has the function of binding astaxanthin which is the best antioxidant, and plays an important role in the body color variation of crustaceans. To investigate the causes of body color variation of the ridgetail white prawn, Exopalaemon carinicauda, the present study obtained four subtypes of crustacyanin gene: C1, C2, A1, and A2. Based on fluorescence quantitative polymerase chain reaction, lipocalin-C1 is mainly expressed in the eyestalk, lipocalin-C2 is in the ventral nerve cord, and lipocalin-A1 and lipocalin-A2 are in subcutaneous adipose tissues. Under the inhibiting effect of Cd2+ stress, the expression of four subtypes first increases and then decreases within 24 h, and reaches the maximum at 6 or 12 h. RNA interference experiments showed a decrease in the expression of lipocalin genes in subcutaneous adipose tissue for each subtype, with the body color changing from transparent to red, and the dark red spots on the epidermis changing to bright red. Moreover, the blue protein in the subcutaneous adipose tissue largely disappeared, based on the light micrographs. In view of these findings, the crustacyanin gene appears to fulfill some function in the resistance to heavy metal stress and body color formation of E. carinicauda.

Deep HDR Imaging via A Non-local Network.

One of the most challenging problems in reconstructing a high dynamic range (HDR) image from multiple low dynamic range (LDR) inputs is the ghosting artifacts caused by the object motion across different inputs. When the object motion is slight, most existing methods can well suppress the ghosting artifacts through aligning LDR inputs based on optical flow or detecting anomalies among them. However, they often fail to produce satisfactory results in practice, since the real object motion can be very large. In this study, we present a novel deep framework, termed NHDRRnet, which adopts an alternative direction and attempts to remove ghosting artifacts by exploiting the non-local correlation in inputs. In NHDRRnet, we first adopt an Unet architecture to fuse all inputs and map the fusion results into a low-dimensional deep feature space. Then, we feed the resultant features into a novel global non-local module which reconstructs each pixel by weighted averaging all the other pixels using the weights determined by their correspondences. By doing this, the proposed NHDRRnet is able to adaptively select the useful information (e.g., which are not corrupted by large motions or adverse lighting conditions) in the whole deep feature space to accurately reconstruct each pixel. In addition, we also incorporate a triple-pass residual module to capture more powerful local features, which proves to be effective in further boosting the performance. Extensive experiments on three benchmark datasets demonstrate the superiority of the proposed NDHRnet in terms of suppressing the ghosting artifacts in HDR reconstruction, especially when the objects have large motions.

Cloning and functional study of lipocalin: retinol-binding protein-like gene family of the ridgetail white prawn, Exopalaemon carinicauda.

Lipocalin is a large family with complex functions including retinol-binding protein (RBP), crustacyanin (CRCN), apolipoprotein D, etc. In shrimps, it is well known that CRCN is related to body color. Recently, retinoic acid/retinol-binding protein was found in shrimp. However, little is known about the function of RBP and relationships among the gene members of lipocalin in shrimps. Based on the transcriptome sequences responding to starvation stress, three genes of the lipocalin-retinol-binding protein-like gene family (lipocalin-1, lipocalin-2, and lipocalin-3) were cloned by RACE from the ridgetail white prawn, Exopalaemon carinicauda. Homology analysis showed that these three genes had high similarity with the known insect apolipoprotein D gene and vertebrate retinol-binding protein gene, and they are of the same type in terms of evolution. Fluorescence quantitative PCR showed that the above three genes were mainly expressed in the ventral nerve cord of E. carinicauda. The expression characteristics of the three genes at different developmental stages showed that they were more highly expressed at the larval stage, which suggests that they might be related to embryonic and larval development. The RNA interference tests showed that after silencing lipocalin-1 and lipocalin-3, the body color of individual shrimps turned slightly red and the blue pigment in the epidermis largely disappeared, but no significant change took place in the appearance of individuals after silencing lipocalin-2. In addition, on the 6th and 16th days of interference, dead shrimps appeared in the lipocalin-1 and lipocalin-3 interference groups. The dead shrimps had hard crusts and remained in a molting posture. Totally, this study showed that the retinol-binding protein-like gene obtained in this study had certain biological functions in the growth and development and body color formation as CRCN; in addition, it also plays a role in nerve system and molting of E. carinicauda.