Cholangiocarcinoma (CCA) has a poor prognosis and only limited palliative treatment options. The deficiency of adiponectin and adenosine monophosphate-activated protein kinase (AMPK) signaling was reported in several malignancies, but the alteration of these proteins in CCA is still unclear. This study aimed to assess the role of adiponectin and AMPK signaling in CCA. Furthermore, AdipoRon, a novel adiponectin receptor (AdipoR) agonist, was evaluated in vitro and in vivo as a new anti-tumor therapy for CCA. The expression of AdipoR1 and p-AMPKα in human tissue microarrays (TMAs) was evaluated by immunohistochemistry staining (IHC). The effect of 2-(4-Benzoylphenoxy)-N-[1-(phenylmethyl)-4-piperidinyl]-acetamide (AdipoRon) was investigated in vitro with proliferation, crystal violet, migration, invasion, colony formation, senescence, cell cycle and apoptosis assays and in vivo using a CCA engineered mouse model (AlbCre/LSL-KRASG12D/p53L/L). RT-qPCR and western blot methods were applied to study molecular alterations in murine tissues. AdipoR1 and p-AMPKα were impaired in human CCA tissues, compared to adjacent non-tumor tissue. There was a positive correlation between the AdipoR1 and p-AMPKα levels in CCA tissues. Treatment with AdipoRon inhibited proliferation, migration, invasion and colony formation and induced apoptosis in a time- and dose-dependent manner in vitro (p<0.05). In addition, AdipoRon reduced the number of CCA and tumor volume, prolonged survival, and decreased metastasis and ascites in the treated group compared to the control group (p<0.05). AdipoR1 and p-AMPKα are impaired in CCA tissues, and AdipoRon effectively inhibits CCA in vitro and in vivo. Thus, AdipoRon may be considered as a potential anti-tumor therapy in CCA.

The Indochinese thick-thumbed bat, Glischropus bucephalus, was described in 2011, but its molecular genetics (and the genetics of the whole genus Glischropus) are still poorly studied. We defined and annotated the complete mitogenome of Glischropus bucephalus (Chiroptera: Vespertilionidae) from Vietnam. The complete mitogenome is 17,023 bp in total length, which includes 13 complete protein-coding genes, 22 tRNA genes, 2 rRNA, and one non-coding region (the origin of replication). The nucleotide composition is 33.2% A, 29.7% T, 13.6% G, and 23.5% C. The mitochondrial protein-coding genes use the standard start codon (ATN), one complete stop codon (TAA), and two incomplete stop codons (TA- and T-). The phylogenetic analysis confirmed that the genus Glischropus belongs to the Pipistrellini tribe and revealed that Glischropus bucephalus is clustered with the “eastern” clade of Pipistrellus, supporting the paraphyletic nature of the latter genus.

Opisthorchis felineus is a food-borne trematode which causes opisthorchiosis and affects mainly the liver and bile ducts of the liver with a possible risk of bile duct carcinogenesis resulting in cholangiocarcinoma. In Russia, O. felineus is mainly endemic in Western Siberia (Ob and Irtysh river basins) and occurs throughout the Volga, Kama, Don, and Dnepr river basins. The prevalence, intensity, and clinical significance of human infections and the incidence of cholangiocarcinoma vary geographically in endemic regions. Currently, there is substantial evidence on genetic variation of O. felineus, but information on the population genetic structure is so far very scarce. Because microsatellite DNA of this parasite is not available, we for the first time isolated sufficient microsatellite loci to examine the genetic diversity and population structure of O. felineus, using multiple nuclear loci approach. A total of ten highly polymorphic microsatellite loci from a constructed enriched genomic DNA library were characterized, using 29 samples representing huge O. felineus metapopulation extended in latitude over 5000km from Middle Europe to Western Siberia. At least three populations can be discerned as result of analysis of the microsatellite loci genetic diversity. Based on the results for the first time, a hypothesis was put forward about the formation of a modern habitat of O. felineus.

The prevalence of hepatitis E virus (HEV) in the Vietnamese population remains underestimated. The aim of the present study was to investigate the seroprevalence of HEV IgG/IgM antibodies and the presence of HEV RNA in blood donors as a part of epidemiological surveillance for transfusion-transmitted viruses. Serum samples from blood donors (n = 553) were analysed for markers of past (anti-HEV IgG) and recent/ongoing (anti-HEV IgM) HEV infections. In addition, all serum samples were subsequently tested for HEV RNA positivity. The overall prevalence of anti-HEV IgG was 26.8% (n = 148/553), while the seroprevalence of anti-HEV IgM was 0.5% (n = 3/553). Anti-HEV IgG seroprevalence in male and female donors was similar (27.1% and 25.5%, respectively). A higher risk of hepatitis E exposure was observed with increasing age. None of the blood donors were HEV RNA positive, and there was no evidence of HEV viraemia. Although the absence of HEV viraemia in blood donors from Northern Vietnam is encouraging, further epidemiological surveillance in other geographical regions is warranted to rule out transfusion-transmitted HEV.

Abstract Myotis muricola species group, being common and widespread across South-East Asia and Australasia, is highly complicated from a taxonomy point, and a combined use of different methods is required to solve subjects of its phylogeny, taxonomy and species delimitation. We try to use nuclear DNA for clarification of the taxonomic position and status of the Moluccan whiskered bat, Myotis ater, and in particular its population from mainland Asia mainland Asia. Following our results, individual nuclear markers showed weak phylogenetic signal and commonly provide controversial and low-supported topologies. The combined analysis of several nuclear genes gives a tree topology similar to the mitochondrial one, but with greatly smaller distances. Mitochondrial data, as well as morphometric data, show a separation of M. ater from M. muricola and, at the same time, a similar level of diversification between island and continental populations of M. ater. Unfortunately, nuDNA data at our disposal is not enough to come to reliable conclusions, but we may assume that continental Asia is inhabited by an undescribed taxon related to M. ater.

Peliosanthes linearifolia, a new species of Asparagaceae, is described and illustrated. The species was discovered in 2022 in Quang Nam Province, southern Vietnam. Peliosanthes linearifolia is remarkable for its linear to narrowly lanceolate leaves that are less than 1.3 cm wide. Such leaves were previously known only in P. graminea. Based on the floral characters of the new species, we assign it to the Peliosanthes teta species group. Peliosanthes linearifolia differs from P. teta, P. graminea and the other species of the group in the following combination of morphological traits: stoloniform rhizome, flowers solitary in axils of all primary bracts of inflorescence (i.e. inflorescence is a raceme), violet flowers and prominently lobed apex of the androecial corona.

It is assumed that host defense systems eliminating the pathogen and regulating tissue damage make a strong impact on the outcome of tuberculosis (TB) disease and that these processes are affected by rifampicin (RIF) resistance-conferring mutations of Mycobacterium tuberculosis (Mtb). However, the host responses to the pathogen harboring different mutations have not been studied comprehensively in clinical settings. We analyzed clinico-epidemiological factors and blood transcriptomic signatures associated with major rpoB mutations conferring RIF resistance in a cohort study. Demographic data were collected from 295 active pulmonary TB patients with treatment history in Hanoi, Vietnam. When recruited, drug resistance-conferring mutations and lineage-specific variations were identified using whole-genome sequencing of clinical Mtb isolates. Before starting retreatment, total RNA was extracted from the whole blood of HIV-negative patients infected with Mtb that carried either the rpoB H445Y or rpoB S450L mutation, and the total RNA was subjected to RNA sequencing after age-gender matching. The individual RNA expression levels in the blood sample set were also measured using real-time RT-PCR. Logistic and linear regression models were used to assess possible associations. In our cohort, rpoB S450L and rpoB H445Y were major RIF resistance-conferring mutations [32/87 (36.8%) and 15/87 (17.2%), respectively]. H445Y was enriched in the ancient Beijing genotype and was associated with nonsynonymous mutations of Rv1830 that has been reported to regulate antibiotic resilience. H445Y was also more frequently observed in genetically clustered strains and in samples from patients who had received more than one TB treatment episode. According to the RNA sequencing, gene sets involved in the interferon-γ and-α pathways were downregulated in H445Y compared with S450L. The qRT-PCR analysis also confirmed the low expression levels of interferon-inducible genes, including BATF2 and SERPING1, in the H445Y group, particularly in patients with extensive lesions on chest X-ray. Our study results showed that rpoB mutations as well as Mtb sublineage with additional genetic variants may have significant effects on host response. These findings strengthen the rationale for investigation of host-pathogen interactions to develop countermeasures against epidemics of drug-resistant TB.

The coronavirus disease 2019 (COVID-19) pandemic resulted in a race to develop effective treatments largely through drug repurposing via adaptive platform trials on a global scale. Drug repurposing trials have focused on potential antiviral therapies aimed at preventing viral replication, anti-inflammatory agents, antithrombotic agents and immune modulators through a number of adaptive platform trials. Living systematic reviews have also enabled evidence synthesis and network meta-analysis as clinical trial data emerge globally. Recent published literature. Corticosteroids and immunomodulators that antagonize the interleukin-6 (IL-6) receptor have been shown to play a critical role in modulating inflammation and improving clinical outcomes in hospitalized patients. Inhaled budesonide reduces the time to recovery in older patients with mild-to-moderate COVID-19 managed in the community. The clinical benefit of remdesivir remains controversial with conflicting evidence from different trials. Remdesivir led to a reduction in time to clinical recovery in the ACTT-1 trial. However, the World Health Organization SOLIDARITY and DISCOVERY trial did not find a significant benefit on 28-day mortality and clinical recovery. Other treatments currently being investigated include antidiabetic drug empagliflozin, antimalarial drug artesunate, tyrosine kinase inhibitor imatinib, immunomodulatory drug infliximab, antiviral drug favipiravir, antiparasitic drug ivermectin and antidepressant drug fluvoxamine. The timing of therapeutic interventions based on postulated mechanisms of action and the selection of clinically meaningful primary end points remain important considerations in the design and implementation of COVID-19 therapeutic trials.

AbstractWe reviewed the systematics of Lycodon striatus (Shaw, 1802), including all available name‐bearing types of its synonyms after evaluating phylogeographic (genetics), morphological (morphometry, meristic, and hemipenes), osteological and distribution evidence. Lycodon striatus sensu lato is widely distributed throughout South and Central Asia and mimics elapids. Based on phylogenetic analyses of mitochondrial DNA, we demonstrate that populations from (i) eastern and central Peninsular India plus Sri Lanka and (ii) south‐western parts of Central Asia form two different clades representing two distinct species: L. striatus sensu stricto and L. bicolor comb. nov. respectively. These two clades are sisters to L. deccanensis (in the case of L. striatus) and L. jara (in the case of L. bicolor) and together form two main sister radiations. Although the external morphological variability is high in both species, the genetic variability is higher only in L. striatus but not distinct enough to represent more than one species if using the phylogenetic or biological species concept. The phylogeny of the L. aulicus group hints at Sri Lankan L. striatus, likely having evolved in continental Asia through a probable overland dispersal across the Bay of Bengal (present Palk Strait) into Sri Lanka. This dispersal may have been facilitated by low sea levels during the Pleistocene glaciations when Sri Lanka was connected to mainland India. After considering genetic divergence (with a p‐distance of 1.8%–2.1% in the mitochondrial cytochrome b gene) and morphological evidence, we synonymize the Sri Lankan subspecies, L. s. sinhaleyus Deraniyagala, 1955, with L. striatus sensu stricto. The eastern and central Indian L. striatus (i.e. L. striatus sensu stricto) is morphologically distinct and deeply divergent genetically compared to Tajik and Pakistani L. bicolor with a p‐distance of 13.6% in cytochrome b gene (mtDNA). Interestingly, L. bicolor is conspecific (p‐distance 1.4%) with L. mackinnoni, a western Himalayan endemic, and it reveals intraspecific clinal variation.

BackgroundRotavirus A (RVA) infections remain a major cause of severe acute diarrhea affecting children worldwide. To date, rapid diagnostic tests (RDT) are widely used to detect RVA. However, paediatricians question whether the RDT can still detect the virus accurately. Therefore, this study aimed to evaluate the performance of the rapid rotavirus test in comparison to the one-step RT-qPCR method.MethodsA cross-sectional study was conducted in Lambaréné, Gabon, from April 2018 to November 2019. Stool samples were collected from children under 5 years of age with diarrhoea or a history of diarrhoea within the last 24 h, and from asymptomatic children from the same communities. All stool samples were processed and analysed using the SD BIOLINE Rota/Adeno Ag RDT against a quantitative reverse transcription PCR (RT-qPCR), which is considered the gold standard.ResultsFor a total of 218 collected stool samples, the overall sensitivity of the RDT was 46.46% (confidence interval (CI) 36.38–56.77), with a specificity of 96.64% (CI 91.62–99.08) compared to one-step RT-qPCR. After confirming the presence or absence of RVA gastroenteritis, the RDT showed suitable results in detecting rotavirus A-associated disease, with a 91% concordance with the RT-qPCR. Furthermore, the performance of this test varied when correlated with seasonality, symptoms, and rotavirus genotype.ConclusionThis RDT showed high sensitivity and was suitable for the detection of RVA in patients with RVA gastroenteritis, although some asymptomatic RVA shedding was missed by RT-qPCR. It could be a useful diagnostic tool, especially in low-income countries.