Background. Renal fibrosis is a common pathological symptom of chronic kidney disease (CKD). Many studies support that mitochondrial dysfunction and endoplasmic reticulum (ER) stress are implicated ...in the pathogenesis of CKD. In our study, we investigated the benefits and underlying mechanisms of Mito-TEMPO on renal fibrosis in 5/6 nephrectomy mice. Methods. Mice were randomly divided into five groups as follows: control group, CKD group, CKD + Mito-TEMPO (1 mg·kg−1·day−1) group, CKD + Mito-TEMPO (3 mg·kg−1·day−1) group, and Mito-TEMPO group (3 mg·kg−1·day−1). Renal fibrosis was evaluated by PAS, Masson staining, immunohistochemistry, and real-time PCR. Oxidative stress markers such as SOD2 activity and MDA level in serum and isolated mitochondria from renal tissue were measured by assay kits. Mitochondrial superoxide production was evaluated by MitoSOX staining and Western blot. Mitochondrial dysfunction was assessed by electron microscopy and real-time PCR. ER stress-associated protein was measured by Western blot. Results. Impaired renal function and renal fibrosis were significantly improved by Mito-TEMPO treatment. Furthermore, inflammation cytokines, profibrotic factors, oxidative stress markers, mitochondrial dysfunction, and ER stress were all increased in the CKD group. However, these effects were significantly ameliorated in the Mito-TEMPO treatment group. Conclusions. Mito-TEMPO ameliorates renal fibrosis by alleviating mitochondrial dysfunction and endoplasmic reticulum stress possibly through the Sirt3-SOD2 pathway, which sheds new light on prevention of renal fibrosis in chronic kidney disease.
Metarhizium is a group of insect-pathogenic fungi that can produce insecticidal metabolites, such as destruxins. Interestingly, the acridid-specific fungus Metarhizium acridum (MAC) can kill locusts ...faster than the generalist fungus Metarhizium robertsii (MAA) even without destruxin. However, the underlying mechanisms of different pathogenesis between host-generalist and host-specialist fungi remain unknown. This study compared transcriptomes and metabolite profiles to analyze the difference in responsiveness of locusts to MAA and MAC infections. Results confirmed that the detoxification and tryptamine catabolic pathways were significantly enriched in locusts after MAC infection compared with MAA infection and that high levels of tryptamine could kill locusts. Furthermore, tryptamine was found to be capable of activating the aryl hydrocarbon receptor of locusts (LmAhR) to produce damaging effects by inducing reactive oxygen species production and immune suppression. Therefore, reducing LmAhR expression by RNAi or inhibitor (SR1) attenuates the lethal effects of tryptamine on locusts. In addition, MAA, not MAC, possessed the monoamine oxidase (Mao) genes in tryptamine catabolism. Hence, deleting MrMao-1 could increase the virulence of generalist MAA on locusts and other insects. Therefore, our study provides a rather feasible way to design novel mycoinsecticides by deleting a gene instead of introducing any exogenous gene or domain.
DEK and miR-5100 play critical roles in many steps of cancer initiation and progression and are directly or indirectly regulated by most promoters and repressors. LEF1-AS1 as a long non-coding RNA ...can regulate tumor development through sponge miRNA. The effect and regulatory mechanism of DEK on autophagy and apoptosis in gastric cancer (GC), and the role between miR-5100 and DEK or miR-5100 and LEF1-AS1 are still unclear. Our study found that DEK was highly expressed in gastric cancer tissues and cell lines, and knockdown of DEK inhibited the autophagy of cells, promoted apoptosis, and suppressed the malignant phenotype of gastric cancer. DEK regulates autophagy and apoptosis through the AMPK/mTOR signaling pathway. In addition, miR-5100 inhibits autophagy and promotes apoptosis in GC cells while LEF1-AS1 had the opposite effect. Studies have shown that miR-5100 acts by targeting the 3'UTR of DEK, and LEF1-AS1 regulates the expression of miR-5100 by sponging with mIR-5100. In conclusion, our results found that LEF1-AS1 and miR-5100 sponge function, and the miR-5100/DEK/AMPK/mTOR axis regulates autophagy and apoptosis in gastric cancer cells.
The stress of living conditions, similar to infections, alters animal immunity. High population density is empirically considered to induce prophylactic immunity to reduce the infection risk, which ...was challenged by a model of low connectivity between infectious and susceptible individuals in crowded animals. The migratory locust, which exhibits polyphenism through gregarious and solitary phases in response to population density and displays different resistance to fungal biopesticide (Metarhizium anisopliae), was used to observe the prophylactic immunity of crowded animals. We applied an RNA-sequencing assay to investigate differential expression in fat body samples of gregarious and solitary locusts before and after infection. Solitary locusts devoted at least twice the number of genes for combating M. anisopliae infection than gregarious locusts. The transcription of immune molecules such as pattern recognition proteins, protease inhibitors, and anti-oxidation proteins, was increased in prophylactic immunity of gregarious locusts. The differentially expressed transcripts reducing gregarious locust susceptibility to M. anisopliae were confirmed at the transcriptional and translational level. Further investigation revealed that locust GNBP3 was susceptible to proteolysis while GNBP1, induced by M. anisopliae infection, resisted proteolysis. Silencing of gnbp3 by RNAi significantly shortened the life span of gregarious locusts but not solitary locusts. By contrast, gnbp1 silencing did not affect the life span of both gregarious and solitary locusts after M. anisopliae infection. Thus, the GNBP3-dependent immune responses were involved in the phenotypic resistance of gregarious locusts to fungal infection, but were redundant in solitary locusts. Our results indicated that gregarious locusts prophylactically activated upstream modulators of immune cascades rather than downstream effectors, preferring to quarantine rather than eliminate pathogens to conserve energy meanwhile increasing the "distance" of infectious and target individuals. Our study has obvious implications for bio-pesticides management of crowded pests, and for understanding disease epidemics and adaptiveness of pathogens.
The genus
Weissella
is attracting an increasing amount of attention because of its multiple functions and probiotic potential. In particular, the species
Weissella confusa
is known to have great ...potential in industrial applications and exhibits numerous biological functions. However, the knowledge on this bacterium in insects is not investigated. Here, we isolated and identified
W. confusa
as the dominant lactic acid bacteria in the gut of the migratory locust. We named this strain
W. confusa
LM1, which is the first genome of an insect-derived
W. confusa
strain with one complete chromosome and one complete plasmid. Among all
W. confusa
strains,
W. confusa
LM1 had the largest genome. Its genome was the closest to that of
W. confusa
1001271B_151109_G12, a strain from human feces. Our results provided accurate evolutionary relationships of known
Weissella
species and
W. confusa
strains. Based on genomic analysis, the pan-genome of
W. confusa
is in an open state. Most strains of
W. confusa
had the unique genes, indicating that these strains can adapt to different ecological niches and organisms. However, the variation of strain-specific genes did represent significant correlations with their hosts and ecological niches. These strains were predicted to have low potential to produce secondary metabolites. Furthermore, no antibiotic resistance genes were identified. At the same time, virulence factors associated with toxin production and secretion system were not found, indicating that
W. confusa
strains were not sufficient to perform virulence. Our study facilitated the discovery of the functions of
W. confusa
LM1 in locust biology and their potential application to locust management.
Traditionally, industrial processes produce wastes that, even though often containing useful materials, are discarded, contributing to environmental pollution and depletion of natural resources. An ...example of such wastes are brines, flows of concentrated salts, produced in water treatment processes, which are now routinely discharged into receiving water bodies. Brines however can also be considered as flows of reusable materials which should be recovered, and the Zero Brine cooperation project aims to develop processes for that purpose. For a demineralized water production plant in the port of Rotterdam (the Netherlands), a closed water processing cycle was proposed to treat the large volume of spent Ion Exchange (IEX) regenerant brine which, apart from recovering demineralized water, is also intended to produce magnesium (Mg2+) and calcium (Ca2+) salts, with the highest purity possible, from the otherwise discharged brine. The process scheme includes nanofiltration (NF) for separating mono- and multivalent ions, followed by sequential chemical precipitation of Mg2+ and Ca2+ ions from the NF concentrate, and production of demineralized water by evaporation of the NF permeate. The concentrate of monovalent ions produced in the evaporator, essentially a concentrated sodium chloride solution, in its turn might be reused for IEX regeneration. Part of the supernatant of the sequential precipitation may be fed to the evaporator as well, but bleeding the other part of this supernatant is essential in order to maintain process stability, avoid accumulation of minor pollutants, and reduce scaling. In this study, various scenarios to operate the process were modeled, using PHREEQC and Excel. According to the simulation results, recovery of ≈97% of Mg2+ and Ca2+ is possible, the latter with a higher purity than the former. The main factors affecting the results are the concentration of carbonate present in the spent IEX regenerant, as well as characteristics of the NF membrane and the dosing of sodium hydroxide in the sequential precipitation steps. The results of the simulations were used for the design and operation of a pilot plant, comprising all mentioned process steps.
Objective The 9-item Patient Health Questionnaire (PHQ-9) was used to screen the depression status of inpatients with liver disease in the Infection Department of a grade A hospital, and nursing ...interventions were taken for patients with moderate and severe depression during hospitalization, so as to reduce the depression of patients with liver disease during hospitalization and promote their mental health and rehabilitation. Methods Using PHQ-9 for depression screening, 163 hospitalized patients with liver diseases in the Infection Department were evaluated from August 1, 2021 to December 31, 2021, and the data were analyzed. According to the results of PHQ-9 depression screening scale, patients with moderate and severe liver disease depression were given 15 days of nursing interventions. Results The results showed that there were 63 (38. 65%)patients with depression, of which 39(61. 90%) cases of mild depression, 15(23. 81%) cases of moderate depression, 7(11. 11%)cases of moderate to severe depression, and
Recognizing proteins via the production of highly specific monoclonal antibodies (mAbs) is crucial to identifying proteins for proteomic research. However, traditional mAb generation is ...time-consuming with low efficiency. In this study, we assessed the high throughput method of producing mAbs by immunizing mice with multiple antigens in order to obtain hybridomas against these multiple antigens in one cell fusion. We selected eight proteins that play important roles in human physiological or pathological processes. These proteins were mixed and simultaneously administered to one mouse. We observed the immunizing period for 10 d, and determined the effect of liquid medium and semi-solid medium in hybridoma generation. As a result, all eight immunogens induced antibodies in the immunized mouse in one cell fusion, we obtained hybridomas specific to all eight proteins by enzyme-linked immuno sorbent assay (ELISA) screening, hybridomas against five out of eight showed specific positive in Western-blotting assays. This indicates that we generated mAbs specific to eight proteins in one cell fusion, greatly increasing the efficiency of mAb generation. Furthermore, we observed that hybridomas selected from the liquid medium and semi-solid medium showed different reactivity to antigens. Our study established high-throughput and time-saving methods for production of mAbs. These results provide alternative approaches for increasing the efficacy of mAb generation.
Changes in population density lead to phenotypic differentiation of solitary and gregarious locusts, which display different resistance to fungal pathogens; however, how to regulate their cellular ...immune strategies remains unknown. Here, our stochastic simulation of pathogen proliferation suggested that humoral defense always enhanced resistance to fungal pathogens, while phagocytosis sometimes reduced defense against pathogens. Further experimental data proved that gregarious locusts had significantly decreased phagocytosis of hemocytes compared to solitary locusts. Additionally, transcriptional analysis showed that gregarious locusts promoted immune effector expression (
and
) and reduced phagocytic gene expression (
) and the cytokine tumor necrosis factor (TNF). Interestingly, higher expression of the cytokine TNF in solitary locusts simultaneously promoted
expression and inhibited
and
expression. Moreover, inhibition of TNF increased the survival of solitary locusts, and injection of TNF decreased the survival of gregarious locusts after fungal infection. Therefore, our results indicate that the alerted expression of TNF regulated the immune strategy of locusts to adapt to environmental changes.
Recovery of ammonia (NH3) from residual waters offers various reuse opportunities, such as the production of fertilisers and the generation of electricity and heat. However, simultaneous evaporation ...of water (H2O) during NH3 stripping under vacuum results in diluted recovered NH3 gas with high H2O contents. Whereas porous gas-permeable membranes are already used for vacuum NH3 stripping, the use of non-porous silica-based pervaporation (PV) membranes showed promising results in recent literature, with respect to more selective transfer of NH3 compared to H2O. In this study, we assessed the selectivity of NH3 over H2O transfer (SNH3/H2O) for different types of membranes, under various hydraulic conditions and feed water compositions. The three following membranes were tested: a porous gas-permeable polytetrafluoroethylene (PTFE) membrane, a hydrophilic (Hybrid Silica PV) membrane and a hydrophobic polydimethylsiloxane PV (PDMS PV) membrane.
For the PTFE and the Hybrid Silica PV membrane, SNH3/H2O ranged between 0.1 and 0.4, indicating that the transfer of NH3 was consistently less preferred compared to the transfer of H2O. The preference for H2O over NH3 transfer through the membranes at various hydraulic conditions and feed water compositions can be assigned to the similarity in polarity and kinetic diameter of NH3 and H2O and the low relative concentration of NH3 in the used feed waters (approximately 0.1–1.0 wt%). The PDMS PV membrane showed negligible NH3 transfer and deteriorated rapidly during the NH3 stripping experiments. The SNH3/H2O of both gas-permeable and PV membranes was higher for unsteady than for steady hydraulic conditions. Furthermore, the SNH3/H2O of the both PTFE and the Hybrid Silica decreased when the ionic strength of the feed water increased from 0.0 to 0.8 mol∙L−1 and when the NH3 feed water concentration increased from 1 to 10 g∙L−1. According to the results, the used PV membranes did not show selectivity of NH3 over H2O transfer. In fact, the used PV membranes consistently had a lower SNH3/H2O than the PTFE membrane. Hence, the dense silica-based PV membranes did not allow for the recovery of gaseous NH3 from water, with lower H2O content in the recovered gas, compared to porous PTFE membranes.
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•Assessment of selectivity of transfer of ammonia (NH3) over water (H2O): SNH3/H2O.•SNH3/H2O assessed for porous gas-permeable and dense pervaporation (PV) membranes.•SNH3/H2O assessed for various hydraulic conditions and feed water compositions.•Consistent selectivity for H2O over NH3 transfer for all membranes and conditions: SNH3/H2O < 1.•SNH3/H2O was lower for PV membranes (0.1–0.2) than for gas-permeable membrane (0.2–0.4).
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