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• CCBE1 deficiency predicted poor prognosis of HCC patients. • Hyper-methylation of CpG islands led to decreased CCBE1 expression. • CCBE1 functioned as an inhibitor of mitochondrial fission. • CCBE1 alters DRP1 phosphorylation level at Ser616 through binding TGFβR2. The extracellular matrix (ECM), as an important component of the tumor microenvironment, exerts various roles in tumor formation. Mitochondrial dynamic disorder is closely implicated in tumorigenesis, including hyperfission in HCC. We aimed to determine the influence of the ECM-related protein CCBE1 on mitochondrial dynamics in HCC. Here, we found that CCBE1 was capable of promoting mitochondrial fusion in HCC. Initially, CCBE1 expression was found to be significantly downregulated in tumors compared with nontumor tissues, which resulted from hypermethylation of the CCBE1 promoter in HCC. Furthermore, CCBE1 overexpression or treatment with recombinant CCBE1 protein dramatically inhibited HCC cell proliferation, migration, and invasion in vitro and in vivo. Mechanistically, CCBE1 functioned as an inhibitor of mitochondrial fission by preventing the location of DRP1 on mitochondria through inhibiting its phosphorylation at Ser616 by directly binding with TGFβR2 to inhibit TGFβ signaling activity. In addition, a higher percentage of specimens with higher DRP1 phosphorylation was present in patients with lower CCBE1 expression than in patients with higher CCBE1 expression, which further confirmed the inhibitory effect of CCBE1 on DRP1 phosphorylation at Ser616. Collectively, our study highlights the crucial roles of CCBE1 in mitochondrial homeostasis, suggesting strong evidence for this process as a potential therapeutic strategy for HCC. [ABSTRACT FROM AUTHOR]

Mitochondrial diseases are a group of inherited or acquired metabolic disorders caused by mitochondrial dysfunction which may affect almost all the organs in the body and present at any age. However, no satisfactory therapeutic strategies have been available for mitochondrial diseases so far. Mitochondrial transplantation is a burgeoning approach for treatment of mitochondrial diseases by recovery of dysfunctional mitochondria in defective cells using isolated functional mitochondria. Many models of mitochondrial transplantation in cells, animals, and patients have proved effective via various routes of mitochondrial delivery. This review presents different techniques used in mitochondrial isolation and delivery, mechanisms of mitochondrial internalization and consequences of mitochondrial transplantation, along with challenges for clinical application. Despite some unknowns and challenges, mitochondrial transplantation would provide an innovative approach for mitochondrial medicine. This review presents different techniques used in mitochondrial isolation and delivery, mechanisms of mitochondrial internalization and consequences of mitochondrial transplantation, along with challenges for clinical application. [Display omitted] [ABSTRACT FROM AUTHOR]

Based on a long-term field investigation in the five provincial regions of Southwest China between 2001 and 2019, the present paper studied the infestation and related ecology of chigger mites (chiggers) on the large Chinese vole (Eothenomys miletus), an endemic and dominant rodent species in the regions. A total of 52331 chiggers were collected from 2661 voles, and 52261 mites were identified as 185 species and 13 genera in the family Trombiculidae with very high species diversity. The identified 185 chigger species on E. miletus (a single rodent species) even exceeded those recorded in some countries. The overall infestation prevalence (P m = 53.96%), mean abundance (MA = 19.64) and mean intensity (MI = 36.39) on E. miletus were much higher than those on some other rodent species in the same regions. Although the species composition showed a moderate similarity (J = 0.63) between male and female hosts (E. miletus), the infestation indices (P m = 56.25%, MA = 21.67) of chiggers on male hosts were higher than those on the females (P m = 51.23%, MA = 17.09) (P < 0.05). Two dominant chigger species, Leptotrombidium scutellare (C r = 19.17%) and L. sinicum (C r = 11.06%), showed an aggregated distribution pattern among different individuals of their host E. miletus , and a relatively high degree of positive association existed between the two dominant chigger species with PCC = 0.57, DI = 0.60 and OI = 0.62 (x 2 = 857.46, P < 0.001). Leptotrombidium d ensipunctatum , Walchia koi , Helenicula hsui , L. scutellare and W. ewingi showed a high degree of environmental adaptability to their environments with high niche breadths. The theoretical curve of the species abundance distribution of chigger community on E. miletus was successfully fitted with Preston's lognormal distribution model. Based on the theoretical curve fitting, the expected total number of chigger species on E. miletus was roughly estimated to be 223 species, and 38 chigger species were probably missed in the sampling investigation. [Display omitted] • Chiggers are the common ectoparasites of rodents and vector of scrub typhus, Eothenomys miletus is the reservoir host and infectious source of zoonoses. • The dominant chigger specie, Leptotrombidium scutellare , is one of the main and powerful vectors of scrub typhus in China. • To study the chigger mites of E. miletus voles in such a wide geographical region. [ABSTRACT FROM AUTHOR]

Based on a long-term field investigation on chigger mites in southwest China from 2001 to 2019, the present study analyzed the infestation and distribution of chigger mites on the Chevrieri's field mouse (Apodemus chevrieri) in the region. A total of 12,516 individuals of chigger mites were collected from 1981 A. chevrieri mice, and 12,281 chiggers were identified as 107 species, 11 genera and 3 subfamilies in 2 families, which revealed a high species diversity of the mites on A. chevrieri mice. Of 1981 A. chevrieri mice, 633 ones were infested with chiggers with a relatively high overall prevalence (P M = 31.95%), mean abundance (MA = 6.32) and mean intensity (MI = 19.77). Of the 107 chigger species identified from A. chevrieri mice, three ones were the most dominant and they were Leptrombidium scutellare , L. densipunctatum and L. cricethrionis , which showed aggregated distribution among different individuals of the mice. A slightly positive association existed between every two dominant chigger species, which implied that the dominant chigger species tend to co-exist on A. chevrieri. The infestations of A. chevrieri with chiggers varied in different latitudes, altitudes and landscapes and they showed some heterogeneity along different environmental gradients. The logistic regression analysis showed that the risk factors for chigger infestations on A. chevrieri were landscapes, ages and altitudes, which implied that the environmental factors and host ages could influence the infestations of the mice with the mites. A theoretical curve of the species abundance distribution of chigger mites on A. chevrieri was successfully fitted by Preston's lognormal model, suggesting that the species abundance distribution conforms to the lognormal distribution pattern. The expected total species of chigger mites on A. chevrieri was roughly estimated to be 136 species and about 29 rare chigger species were probably missed in the sampling field investigation. [Display omitted] • Infestation and distribution of chigger mites on Apodemus chevrieri in Southwest China. • Risk factors of infestations of Apodemus chevrieri with chigger mites. • It is the first time to study the chigger mites of Apodemus chevrieri in such a wide geographical region. [ABSTRACT FROM AUTHOR]