Phylogeny, character evolution, and biogeography of the fern genus Bolbitis (Dryopteridaceae).

Bolbitis is a pantropical fern genus of Dryopteridaceae with ca. 80 species mainly in tropical Asia. Earlier studies confirmed the monophyly of Bolbitis when Mickelia is excluded and identified three major clades in Bolbitis. However, earlier studies are based on relatively small sampling and the majority of Asian species are not sampled. In this study, DNA sequences of three plastid markers of 169 accessions representing ca. 68 (85 % of total) species of Bolbitis in nine out of the 10 series recognized by Hennipman (1977), and 54 accessions representing the five remaining bolbitidoid genera are used to infer a global phylogeny with a focus on Asian species. The major results include: (1) Bolbitis is strongly supported as monophyletic; (2) species of Bolbitis are resolved into four major clades and their relationships are: the Malagasy/Mascarene clade is sister to the rest, followed by the African clade which is sister to the American clade + the Asian clade; (3) six well-supported subclades are identified in the most speciose Asian clade; (4) the free-veined Egenolfia is embedded in Bolbitis and is paraphyletic in relation to species with anastomosing venation; (5) three series sensu Hennipman (1977), B. ser. Alienae, B. ser. Egenolfianae, and B. ser. Heteroclitae, are paraphyletic or polyphyletic; (6) evolution of six morphological characters is analyzed and free venation is found to have evolved from anastomosing venation and reversed to free venation in Bolbitis; and (7) biogeographical implications are drawn and it is shown that a single recent dispersal from Asia resulted in continental disjunction of closely related ferns of Bolbitis between Africa and America.

[Regulatory effect of the zinc transporter Zip2 on cardiomyocyte mitochondrial respiration function after cardiac ischemia-reperfusion injury in mice].

The aim of the present study was to investigate the effect of zinc transporter Zip2 (SLC39A2) on mitochondrial respiration during myocardial ischemia/reperfusion (I/R) and the underlying mechanisms. An in vivo myocardial I/R model was established in mice by ligation of left anterior descending coronary artery. Cardiac zinc concentration was measured by inductively coupled plasma-optical emission spectrometer (ICP-OES), and the mitochondrial respiratory function and oxidative phosphorylation were determined by high-resolution respirometry (Oxygraph-2K). The phosphorylation levels of STAT3 and ERK in myocardial tissue were detected by Western blot. The results showed that, compared with the sham group, cardiac zinc concentration in myocardium was decreased in wild-type mice and further reduced in Zip2 knockout mice after I/R. Mitochondrial respiratory control rate (RCR) and oxidative phosphorylation were decreased in Zip2 knockout mice and worsened by I/R. Phosphorylation levels of STAT3 (Ser727) and ERK were significantly decreased in Zip2 knockout mice after I/R. In I/R myocardial tissue, STAT3 overexpression significantly improved the mitochondrial respiratory function, while STAT3 dominant negative mutant (STAT3 S727A) inhibited mitochondrial respiratory function. Moreover, the impairment of mitochondrial function by Zip2 knockout was reversed by STAT3 overexpression. These results suggest that Zip2 regulates mitochondrial respiration via phosphorylation of STAT3 during myocardial I/R, which may represent the underlying mechanism of Zip2 cardioprotection against I/R injury.

Association between dietary inflammatory potential and frailty is mediated by inflammation among patients with colorectal cancer: A cross-sectional study.

Patients with colorectal cancer (CRC) are at high risk of frailty, leading to reduced quality of life and survival. Diet is associated with frailty in the elderly through regulating inflammation. Thus, we hypothesized that dietary inflammatory potential (as assessed by dietary inflammatory index [DII]) might be associated with frailty in patients with CRC through regulating inflammatory biomarkers. A total of 231 patients with CRC were included in this cross-sectional study. Dietary intake was evaluated by 3-day, 24-hour dietary recalls, and frailty status was assessed in accordance with the Fried frailty criteria. Plasma inflammatory cytokines were determined in 126 blood samples. A total of 67 patients (29.0%) were frail, with significantly higher DII scores than nonfrail patients, accompanied with significantly increased interleukin-6 (IL-6) and decreased interleukin-10 (IL-10) concentrations. Each 1-point increase of DII was related to a 25.0% increased risk of frailty. IL-6 was positively correlated with frailty and DII, whereas IL-10 was negatively correlated. After adjusting for age, sex, body mass index, education level, smoking status, and energy, mediation analysis revealed that the association between DII and frailty was significantly mediated by IL-6 (average causal mediation effect [ACME], 0.052; 95% confidence interval, 0.020-0.087; P = .002) and IL-10 (ACME, 0.025; 95% confidence interval, 0.004-0.063; P = .016). The ρ values for the sensitivity measure at which estimated ACMEs were zero were 0.3 and -0.2 for IL-6 and IL-10, respectively. Therefore, a pro-inflammatory diet was associated with frailty in patients with CRC possibly in part by affecting circulating IL-6 and IL-10 concentrations.

The complete chloroplast genome of Eastern Asian fern Bolbitis laxireticulata (Dryopteridaceae).

Bolbitis laxireticulata is a potential ornamental plant, which is restricted to eastern Asia. Here, we sequenced the complete chloroplast (cp) genome of B. laxireticulata and constructed a phylogenetic cp tree of Dryopteridaceae to study their relationships. The cp genome of B. laxireticulata is 153,093 bp in length, being made up of large single-copy (LSC, 83,169 bp), small single-copy (SSC, 21,538 bp), and a pair of region inverted repeats (IRs, 24,193 bp). It has 124 genes including 83 protein-coding genes, 33 tRNA genes, and eight rRNA genes. With the maximum-likelihood tree indicating, B. laxireticulata is more closely related to B. subcordata.

Curing hemophilia A by NHEJ-mediated ectopic F8 insertion in the mouse.

BACKGROUND: Hemophilia A, a bleeding disorder resulting from F8 mutations, can only be cured by gene therapy. A promising strategy is CRISPR-Cas9-mediated precise insertion of F8 in hepatocytes at highly expressed gene loci, such as albumin (Alb). Unfortunately, the precise in vivo integration efficiency of a long insert is very low (~ 0.1%). RESULTS: We report that the use of a double-cut donor leads to a 10- to 20-fold increase in liver editing efficiency, thereby completely reconstituting serum F8 activity in a mouse model of hemophilia A after hydrodynamic injection of Cas9-sgAlb and B domain-deleted (BDD) F8 donor plasmids. We find that the integration of a double-cut donor at the Alb locus in mouse liver is mainly through non-homologous end joining (NHEJ)-mediated knock-in. We then target BDDF8 to multiple sites on introns 11 and 13 and find that NHEJ-mediated insertion of BDDF8 restores hemostasis. Finally, using 3 AAV8 vectors to deliver genome editing components, including Cas9, sgRNA, and BDDF8 donor, we observe the same therapeutic effects. A follow-up of 100 mice over 1 year shows no adverse effects. CONCLUSIONS: These findings lay the foundation for curing hemophilia A by NHEJ knock-in of BDDF8 at Alb introns after AAV-mediated delivery of editing components.

Antimalarial drug artemisinin extenuates amyloidogenesis and neuroinflammation in APPswe/PS1dE9 transgenic mice via inhibition of nuclear factor-κB and NLRP3 inflammasome activation.

BACKGROUND: The activation of nuclear factor-kappa B (NF-κB) and NLRP3 inflammasome is involved in neuroinflammation, which is closely linked to Alzheimer's disease (AD). In vivo and in vitro studies have suggested that artemisinin shows antiinflammatory effects in inflammation-related diseases. However, the impacts of artemisinin on AD have not been investigated. AIMS: In this study, 5-month-old APPswe/PS1dE9 transgenic mice were treated daily with 40 mg/kg artemisinin for 30 days by intraperitoneal injection to evaluate the effects of artemisinin on AD. RESULTS: We found that artemisinin treatment (1) decreased neuritic plaque burden; (2) did not alter Aß transport across the blood-brain barrier; (3) regulated APP processing via inhibiting ß-secretase activity; (4) inhibited NF-κB activity and NALP3 inflammasome activation in APPswe/PS1dE9 double transgenic mice. CONCLUSIONS: The in vivo study clearly demonstrates that artemisinin has protective effects on AD pathology due to its effects on suppressing NF-κB activity and NALP3 inflammasome activation. Our study suggests that targeting NF-κB activity and NALP3 inflammasome activation offers a valuable intervention for AD.