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A sulfur-containing metal–organic framework, donated as UiO-66-NSMe, was prepared by the post-synthetic modification (PSM) of UiO-66-NH2 with 2-(Methylthio)benzaldehyde, and the successful synthesis of PSM was confirmed by X-ray photoelectron spectroscopy (XPS), FT-IR and 1H NMR studies. According to the characteristics of mercury thiophilic, UiO-66-NSMe could be used as a luminescent sensor for Hg2+ detection with a high selectivity and sensitivity (Ksv = 2.5 × 104 M−1; LOD = 20 nM), which could be attributed to the coordination between sulfur sites and Hg2+ based on XPS results. In practical applications, UiO-66-NSMe yielded satisfactory recovery rates (ranging from 96.1% to 99.5%) when it was employed for detecting Hg2+ in spiked environmental samples. Furthermore, UiO-66-NSMe was successfully employed to detect mercury (II) residues with the in situ rapid nondestructive imaging in simulated fresh agricultural products. Thus, this PSM strategy could provide good guidance for environmental protection methodologies in the future.

BackgroundBovine viral diarrhea is one of the diseases that cause huge economic losses in animal husbandry. Many countries or regions have successively introduced eradication plans, but BVDV still has a high prevalence in the world. This meta-analysis aims to investigate the prevalence and risk factors of BVDV in the world in recent 10 years, and is expected to provide some reference and theoretical basis for BVDV control plans in different regions.MethodRelevant articles published from 2010 to 2021 were mainly retrieved from NCBI, ScienceDirect, Chongqing VIP, Chinese web of knowledge (CNKI), web of science and Wanfang databases.Results128 data were used to analyze the prevalence of BVDV from 2010 to 2021. BVDV antigen prevalence rate is 15.74% (95% CI: 11.35–20.68), antibody prevalence rate is 42.77% (95% CI: 37.01–48.63). In the two databases of antigen and antibody, regions, sampling time, samples, detection methods, species, health status, age, sex, breeding mode, and seasonal subgroups were discussed and analyzed, respectively. In the antigen database, the prevalence of dairy cows in the breed subgroup, ELISA in the detection method subgroup, ear tissue in the sample subgroup, and extensive breeding in the breeding mode were the lowest, with significant differences. In the antibody database, the prevalence rate of dairy cows in the breed subgroup and intensive farming was the highest, with a significant difference. The subgroups in the remaining two databases were not significantly different.ConclusionThis meta-analysis determined the prevalence of BVDV in global cattle herds from 2010 to 2021. The prevalence of BVDV varies from region to region, and the situation is still not optimistic. In daily feeding, we should pay attention to the rigorous and comprehensive management to minimize the spread of virus. The government should enforce BVDV prevention and control, implement control or eradication policies according to local conditions, and adjust the policies in time.

Mitochondria play a multidimensional role in the function and the vitality of the neurological system. From the generation of neural stem cells to the maintenance of neurons and their ultimate demise, mitochondria play a critical role in regulating our neural pathways’ homeostasis, a task that is critical to our cognitive health and neurological well-being. Mitochondria provide energy via oxidative phosphorylation for the neurotransmission and generation of an action potential along the neuron’s axon. This paper will first review and examine the molecular subtleties of the mitochondria’s role in neurogenesis and neuron vitality, as well as outlining the impact of defective mitochondria in neural aging. The authors will then summarize neurodegenerative diseases related to either neurogenesis or homeostatic dysfunction. Because of the significant detriment neurodegenerative diseases have on the quality of life, it is essential to understand their etiology and ongoing molecular mechanics. The mitochondrial role in neurogenesis and neuron vitality is essential. Dissecting and understanding this organelle’s role in the genesis and homeostasis of neurons should assist in finding pharmaceutical targets for neurodegenerative diseases.

Mitophagy is an intracellular mechanism to maintain mitochondrial health by removing dysfunctional mitochondria. The E3 ligase Parkin ubiquitinates the membrane proteins on targeted mitochondria to initiate mitophagy, whereas USP30 antagonizes Parkin-dependent mitophagy by removing ubiquitin from Parkin substrates. The AKT/mTOR signaling is a master regulator of cell proliferation, differentiation, apoptosis, and autophagy. Although mounting evidence suggests that perturbations in the AKT/mTOR signaling pathway may contribute to mitophagy regulation, the specific mechanisms between Parkin/USP30 and AKT/mTOR signaling have not been elucidated. In this study, we employ a set of genetic reagents to investigate the role of Parkin and USP30 in regulating the AKT/mTOR signaling during mitophagy. We demonstrated that, in the setting of mitochondrial stress, the AKT/mTOR signaling is regulated, at least in part, by the activity of Parkin and USP30. Parkin inhibits AKT/mTOR signaling following an in vitro mitochondrial stress, thereby promoting apoptosis. However, USP30 overexpression antagonizes the activity of Parkin to sustain AKT/mTOR activity and inhibit apoptosis. These findings provide new insights into Parkin and USP30’s role in apoptosis and suggest that inhibiting USP30 might provide a specific strategy to synergize with AKT/mTOR inhibitors in cancer treatment.

The 2015 to 2016 outbreak of Zika virus (ZIKV) infections in the Americas coincided with a dramatic increase in neurodevelopmental abnormalities, including fetal microcephaly, in newborns born to infected women. In this study, we observed mitochondrial fragmentation and disrupted mitochondrial membrane potential after 24 h of ZIKV infection in human neural stem cells and the SNB-19 glioblastoma cell line. The severity of these changes correlated with the amount of ZIKV proteins expressed in infected cells. ZIKV infection also decreased the levels of mitofusin 2, which modulates mitochondria fusion. Mitochondrial division inhibitor 1 (Mdivi-1), a small molecule inhibiting mitochondria fission, ameliorated mitochondria disruptions and reduced cell death in ZIKV-infected cells. Collectively, this study suggests that abnormal mitochondrial fragmentation contributes to ZIKV-induced neuronal cell death; rebalancing mitochondrial dynamics of fission-fusion could be a therapeutic strategy for drug development to treat ZIKV-mediated neuronal apoptosis.

Mitochondrial dysfunction is a hallmark of aging and is a major contributor to neurodegenerative diseases and various cardiovascular disorders. Mitophagy, a specialized autophagic pathway to remove damaged mitochondria, provides a critical mechanism to maintain mitochondrial quality. This function has been implicated in a tissue’s ability to appropriately respond to metabolic and to bioenergetic stress, as well as to recover from mitochondrial damage. A global decline in mitophagic flux has been postulated to be linked to pathological alterations that occur in the heart and the brain as well as a general age-dependent decline in organ function. Cellular observation suggests multiple mechanistically distinct pathways converge upon and activate mitophagy. Over the past decade, additional molecular components within mitophagy have been discovered, including several disease-associated genes that are functionally implicated in mitophagy. However, the pathophysiological role of mitophagy, and how it is regulated within normal physiology or various disease states, is less well established. Here, we will review the evidence that a decline in mitophagy contributes to impaired mitochondrial homeostasis and may be particularly detrimental to postmitotic neurons and cardiomyocytes. We will discuss mitophagy’s pathological significance in both neurodegenerative diseases and cardiovascular disorders. Additionally, signaling pathways regulating mitophagy are reviewed, with emphasis placed on how these pathways might contribute to disease progression. Understanding mitophagy’s role in the mechanisms of disease pathogenesis should allow for the development of more efficient strategies to battle pathological conditions associated with mitochondrial dysfunction.

ABSTRACT Candida albicans is an opportunistic fungal pathogen of major clinical concern. The virulence of this pathogen is intimately intertwined with its metabolism. Mitochondria, which have a central metabolic role, have undergone many lineage-specific adaptations in association with their eukaryotic host. A screen for lineage-specific genes identified seven such genes specific to the CTG clade of fungi, of which C. albicans is a member. Each is required for respiratory growth and is integral to expression of complex I, III, or IV of the electron transport chain. Two genes, NUO3 and NUO4, encode supernumerary subunits of complex I, whereas NUE1 and NUE2 have nonstructural roles in expression of complex I. Similarly, the other three genes have nonstructural roles in expression of complex III (QCE1) or complex IV (COE1 and COE2). In addition to these novel additions, an alternative functional assignment was found for the mitochondrial protein encoded by MNE1. MNE1 was required for complex I expression in C. albicans, whereas the distantly related Saccharomyces cerevisiae ortholog participates in expression of complex III. Phenotypic analysis of deletion mutants showed that fermentative metabolism is unable to support optimal growth rates or yields of C. albicans. However, yeast-hypha morphogenesis, an important virulence attribute, did not require respiratory metabolism under hypoxic conditions. The inability to respire also resulted in hypersensitivity to the antifungal fluconazole and in attenuated virulence in a Galleria mellonella infection model. The results show that lineage-specific adaptations have occurred in C. albicans mitochondria and highlight the significance of respiratory metabolism in the pathobiology of C. albicans. IMPORTANCE Candida albicans is an opportunistic fungal pathogen of major clinical concern. The virulence of this pathogen is intimately intertwined with its metabolic behavior, and mitochondria have a central role in that metabolism. Mitochondria have undergone many evolutionary changes, which include lineage-specific adaptations in association with their eukaryotic host. Seven lineage-specific genes required for electron transport chain function were identified in the CTG clade of fungi, of which C. albicans is a member. Additionally, examination of several highly diverged orthologs encoding mitochondrial proteins demonstrated functional reassignment for one of these. Deficits imparted by deletion of these genes revealed the critical role of respiration in virulence attributes of the fungus and highlight important evolutionary adaptations in C. albicans metabolism.

Multi-drug resistance of pathogenic microorganisms is becoming a serious threat, particularly to immunocompromised populations. The high mortality of systematic fungal infections necessitates novel antifungal drugs and therapies. Unfortunately, with traditional drug discovery approaches, only echinocandins was approved by FDA as a new class of antifungals in the past two decades. Drug efflux is one of the major contributors to multi-drug resistance, the modulator of drug efflux pumps is considered as one of the keys to conquer multi-drug resistance. In this study, we combined structure-based virtual screening and whole-cell based mechanism study, identified a natural product, beauvericin (BEA) as a drug efflux pump modulator, which can reverse the multi-drug resistant phenotype of Candida albicans by specifically blocking the ATP-binding cassette (ABC) transporters; meantime, BEA alone has fungicidal activity in vitro by elevating intracellular calcium and reactive oxygen species (ROS). It was further demonstrated by histopathological study that BEA synergizes with a sub-therapeutic dose of ketoconazole (KTC) and could cure the murine model of disseminated candidiasis. Toxicity evaluation of BEA, including acute toxicity test, Ames test, and hERG (human ether-à-go-go-related gene) test promised that BEA can be harnessed for treatment of candidiasis, especially the candidiasis caused by ABC overexpressed multi-drug resistant C. albicans.