Assessment of the antimicrobial and immunomodulatory activity of QS-CATH, a promising therapeutic agent isolated from the Chinese spiny frogs (Quasipaa spinosa).

Cathelicidins are important antimicrobial peptides in various vertebrate species where they are crucial parts of the innate immune system. The current understanding of amphibian cathelicidins is limited, particularly with regard to their immunomodulatory effects. To address this knowledge gap, we produced the cDNA sequence of the cathelicidin gene from a skin transcriptome of the Chinese spiny frog Quasipaa spinosa. The amino acid sequence of the Quasipaa spinosa cathelicidin (QS-CATH) was predicted to consist of a signal peptide, a cathelin domain, and a mature peptide. Comparative analysis of the QS-CATH amino acid sequence with that of other amphibian cathelicidins revealed high variability in the functional mature peptide among amphibians, whereas the cathelin domain was conserved. The QS-CATH gene was expressed in several tissues, with the highest level of expression in the spleen. Upregulation of QS-CATH after Aeromonas hydrophila infection occurred in the kidney, gut, spleen, skin, and liver. Chemically synthesized QS-CATH exhibited pronounced antibacterial activity against Shigella flexneri, Staphylococcus warneri, Escherichia coli, Salmonella enterica, and Listeria monocytogenes. Furthermore, QS-CATH disrupted the cell membrane integrity of S. flexneri, as evidenced by a lactate dehydrogenase release assay, and it hydrolyzed the genomic DNA of S. flexneri. Additionally, QS-CATH elicited chemotaxis and modulated the expression of inflammatory cytokine genes in RAW264.7 mouse leukemic monocyte/macrophage cells. These findings confirm the antimicrobial effects of amphibian cathelicidin and its ability to influence immune cell function. This will expedite the potential utilization of amphibian antimicrobial peptides as therapeutic agents.

Effects of Early-Stage Blood Pressure Variability on the Functional Outcome in Acute Ischemic Stroke Patients With Symptomatic Intracranial Artery Stenosis or Occlusion Receiving Intravenous Thrombolysis.

Background: Studies exploring the relationship between blood pressure (BP) fluctuations and outcome in acute ischemic stroke (AIS) patients treated with intravenous thrombolysis (IVT) are limited. We aimed to investigate the influence of blood pressure variability (BPV) during the first 24 h after IVT on early neurological deterioration (END) and 3-month outcome after IVT in terms of different stroke subtypes. Methods: Clinical data from consecutive AIS patients who received IVT were retrospectively analyzed. The hourly systolic BP of all patients were recorded during the first 24 h following IVT. We calculated three systolic BPV parameters, including coefficient of variability (CV), standard deviation of mean BP (SD) and successive variation (SV), within the first 6, 12, and 24 h after IVT. END was defined as neurological deterioration with an increase in the National Institutes of Health Stroke Scale (NIHSS) score ≥ 4 points within the first 72 h after admission. Follow-up was performed at 90 days after onset, and favorable and poor outcomes were defined as a modified Rankin Scale scores (mRS) of ≤1 or ≥2, respectively. Results: A total of 339 patients, which were divided into those with (intracranial artery stenosis or occlusion group, SIASO group) and without (non-SIASO group) SIASO, were included. Among them, 110 patients (32.4%) were with SIASO. Patients in SIASO group had higher NIHSS on admission and difference in term of mRS at 90 days compared with non-SIASO group (P < 0.001). In SIASO group, patients in favorable outcome group were younger and had lower NIHSS on admission, lower SV-24 h (14.5 ± 4.3 vs. 11.8 ± 3.2, respectively) and lower SD-24 h (12.7 ± 3.8 vs. 10.9 ± 3.3, respectively), compared with patients with poor outcome (all P < 0.05). In the multivariable logistic regression analysis, compared with the lowest SV (SV < 25% quartile), SV50-75% [odds ratio (OR) = 4.449, 95% confidence interval (CI) = 1.231-16.075, P = 0.023] and SV>75% (OR = 8.676, 95% CI = 1.892-39.775, P = 0.005) were significantly associated with poor outcome at 3 months in patients with SIASO, adjusted for age, NIHSS on admission and atrial fibrillation. No BPV parameters were associated with END in SIASO group. In non-SIASO group, there were no significant association between BPV patterns and END or 90-day outcome. Conclusions: SV-24 h had a negative relationship with 3-month outcome in AIS patients with SIASO treated with IVT, indicating that BPV may affect the outcome of AIS.

The complete mitochondrial genome of Hylarana latouchii (Anura: Ranidae) and its phylogenetic analysis.

We reported the complete mitochondrial genome (mitogenome) of broad-folded frog (Hylarana latouchii). This mitogenome is 17,007 bp in size and consists of 13 protein-coding genes, 22 transfer RNAs, two ribosomal RNAs, and one non-coding sequence (D-loop). The total composition was 58.54% A + T and 41.46% G + C (T: 29.31%, C: 27.33%, A: 29.23%, and G: 14.13%). The phylogenetic analysis revealed that H. latouchii formed a clade with other two species of genus Hylarana. This mitogenomic sequence of H. latouchii provides useful data to study its population genetics and phylogeography.

Characterization of the complete mitochondrial genome of the Chong'an Moustache Toad, Leptobrachium liui (Pope, 1947) with a phylogenetic analysis of Megophryidae.

The Chong'an Mustache Toad, Leptobrachium liui (Pope, 1947) is a Chinese endemic species, inhabiting the mountain streams with rich vegetation in southeastern China. The first complete mitochondrial genome (mitogenome) of L. liui was assembled using the data of whole-genome sequencing. The size of the complete mitogenome for L. liui was 17,190 bp, which included 13 PCGs, 23 tRNAs with two concatenated tRNAMet genes, 2 rRNAs, a non-coding region, and a D-loop. The Bayesian tree shows that L. liui was positioned near L. leishanense within the genus Leptobrachium.

Next-generation sequencing yields the complete mitochondrial genome of Microhyla beilunensis (Anura: Microhylidae).

The complete mitochondrial genome (mtDNA) of Microhyla beilunensis (Anura: Microhylidae) was sequenced and annotated. The length of mtDNA sequences of M. beilunensis was 16,721 bp, and encoded 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA) genes, 2 ribosomal RNA (rRNA) genes, and a control region. The overall nucleotide composition of this genome was 29.1% A, 24.5% C, 14.5% G, 31.9% T, with a total A + T content of 61%. Phylogenetic analysis using Bayesian Inference (BI) method revealed that M. beilunensis was closely related with other 8 species from the genus Microhyla. The mtDNA dataset could be utilized for studying the molecular ecology and population genetics of Microhylid frogs.

The advertisement call of the moustache toad Leptobrachium liui Pope, 1947 (Anura: Megophryidae) from eastern China.

The Leptobrachium genus is currently composed of 36 species distributed in Southern China, India, islands of the Sunda Shelf, and the Philippines (Frost 2019). In China, 11 species of the genus Leptobrachium are currently known (AmphibiaChina 2019), of which, the following nine are Chinese endemic: L. bompu (Sondhi Ohler 2011), L. boringii (Liu 1945), L. guangxiense (Fei, Mo, Ye Jiang 2009), L. hainanense (Ye Fei 1993), L. huashen (Fei Ye 2005), L. leishanense (Liu Hu 1973), L. liui (Pope 1947), L. promustache (Rao, Wilkinson Zhang 2006) and L. tengchongense (Yang, Wang Chan 2016). These species have different morphologies, narrow distribution areas, and their taxonomy is subject to controversy (AmphibiaChina 2019). The megophryid genus Leptobrachium was considered to contain two subgenera Vibrissaphora and Leptobrachium (Matsui et al. 2010). Five Leptobrachium species, L. ailaonicum, L. boringii, L. leishanense, L. liui, and L. promustache, were originally classified as Vibrissaphora, based on adult males bearing spines on the upper lip (Fei Ye 2016). However, recent phylogenetic studies showed that Vibrissaphora was not a subgenus and placed within the genus Leptobrachium (Zheng et al. 2008; Matsui et al. 2010).

Adult-onset mitochondrial encephalopathy in association with the MT-ND3 T10158C mutation exhibits unique characteristics: A case report.

BACKGROUND: Mitochondrial diseases are a heterogenous group of multisystemic disorders caused by genetic mutations affecting mitochondrial oxidation function. Brain involvement is commonly found in most cases but rarely as the unique clinical manifestation. Since the knowledge of its clinical manifestation combined with genetic testing is important for preventing misdiagnosis and delay in treatment, we report here how we diagnosed and managed a very unusual case of mitochondrial encephalopathy. CASE SUMMARY: We report a 52-year-old woman with recurrent stroke-like episodes carrying the m.10158T>C mutation in the MT-ND3 gene, which is also responsible for fatal infant-onset Leigh syndrome. Despite the common mutation, the present case featured a distinct clinical and neuroimaging manifestation from Leigh syndrome. This patient presented with sudden onset of right-sided hemiparesis and hemilateral sensory disturbance accompanied by a left temporal cluster-like headache and later developed epilepsy during hospitalization, with no other signs suggestive of myopathy, lactate acidosis, or other systemic symptoms. Brain magnetic resonance imaging revealed variable lesions involving multiple cortical and subcortical regions. Furthermore, a negative genetic test obtained from peripheral blood delayed the diagnosis of mitochondrial disease, which was eventually established through second-generation DNA sequencing using biopsied muscle. CONCLUSION: Based on this report, we suggest that clinicians pursue proper genetic testing for patients when the clinical phenotype is suggestive of mitochondrial diseases.

[Value of lower-limb short latency somatosensory evoked potentials in predicting early death in patients with massive cerebral infarction].

OBJECTIVE: To explore the value of lower-limb short latency somatosensory evoked potentials (SLSEP) in predicting early death in patients with massive cerebral infarction. METHODS: Forty-eight patients of massive cerebral infarction were admitted in the Neurological Intensive Care Unit (NICU) between March 2008 and March 2009, and Glasgow-Pittsburgh coma scale (GPCS) and SLSEP were recorded and graded within 24 h after admission. The patients were divided into survival and death groups (including brain death) according to their short-term prognosis. The correlations of SLSEP and GPCS to the mortality were assessed. RESULTS: A significant correlation was found between SLSEP and the mortality in patients with massive cerebral infarction (r=0.484, P<0.001). The positive predictive value of the SLSEP grade 3 to death was 100%, and the patients with malignant middle cerebral artery infarction (mMCAI) appeared to have a 100% mortality. CONCLUSION: SLSEP grade 3 can be a highly specificity in predicting early death in patients with massive cerebral infarction, and it is also of value in determining the timing of surgical intervention of mMCAI.