Concordant geographic and genetic structure revealed by genotyping‐by‐sequencing in a New Zealand marine isopod

Population genetic structure in the marine environment can be influenced by life‐history traits such as developmental mode (biphasic, with distinct adult and larval morphology, and direct development, in which larvae resemble adults) or habitat specificity, as well as geography and selection. Developmental mode is thought to significantly influence dispersal, with direct developers expected to have much lower dispersal potential. However, this prediction can be complicated by the presence of geophysical barriers to dispersal. In this study, we use a panel of 8,020 SNPs to investigate population structure and biogeography over multiple spatial scales for a direct‐developing species, the New Zealand endemic marine isopod Isocladus armatus. Because our sampling range is intersected by two well‐known biogeographic barriers (the East Cape and the Cook Strait), our study provides an opportunity to understand how such barriers influence dispersal in direct developers. On a small spatial scale (20 km), gene flow between locations is extremely high, suggestive of an island model of migration. However, over larger spatial scales (600 km), populations exhibit a clear pattern of isolation‐by‐distance. Our results indicate that I. armatus exhibits significant migration across the hypothesized barriers and suggest that large‐scale ocean currents associated with these locations do not present a barrier to dispersal. Interestingly, we find evidence of a north‐south population genetic break occurring between Māhia and Wellington. While no known geophysical barrier is apparent in this area, it coincides with the location of a proposed border between bioregions. Analysis of loci under selection revealed that both isolation‐by‐distance and adaption may be contributing to the degree of population structure we have observed here. We conclude that developmental life history largely predicts dispersal in the intertidal isopod I. armatus. However, localized biogeographic processes can disrupt this expectation, and this may explain the potential meta‐population detected in the Auckland region.     

Geographic variation in the skulls of the horseshoe bats,Rhinolophus simulator and R. cf. simulator: Determining the relative contributions of adaptation and drift using geometric morphometrics

The relative contributions of adaptation and genetic drift to morphological diversification of the skulls of echolocating mammals were investigated using two horseshoe bat species, Rhinolophus simulator and R. cf. simulator, as test cases. We used 3D geometric morphometrics to compare the shapes of skulls of the two lineages collected at various localities in southern Africa. Size and shape variation was predominantly attributed to selective forces; the between‐population variance (B) was not proportional to the within‐population variance (W). Modularity was evident in the crania of R. simulator but absent in the crania of R. cf. simulator and the mandibles of both species. The skulls of the two lineages thus appeared to be under different selection pressures, despite the overlap in their distributions. Difference in the crania of R. cf. simulator was centered largely on the nasal dome region of R. cf. simulator but on the cranium and mandibles of R. simulator. It is likely that the size and shape of the nasal dome, which acts as a frequency‐dependent acoustic horn, is more crucial in R. cf. simulator than in R. simulator because of the higher echolocation frequencies used by R. cf. simulator. A larger nasal dome in R. cf. simulator would allow the emission of higher intensity pulses, resulting in comparable detection distances to that of R. simulator. In contrast, selection pressure is probably more pronounced on the mandibles and cranium of R. simulator to compensate for the loss in bite force because of its elongated rostrum. The predominance of selection probably reflects the stringent association between environment and the optimal functioning of phenotypic characters associated with echolocation and feeding in bats.     

Population‐specific responses of an insect herbivore to variation in host‐plant quality

Anthropogenic climate change poses a substantial challenge to many organisms, to which they need to respond to avoid fitness reductions. Investigating responses to environmental change is particularly interesting in herbivores, as they are potentially affected by indirect effects mediated via variation in host‐plant quality. We here use the herbivorous insect Pieris napi to investigate geographic variation in the response to variation in food quality. We performed a common garden experiment using replicated populations from Germany and Italy, and manipulated host quality by growing host plants at different temperature and water regimes. We found that feeding on plants grown at a higher temperature generally diminished the performance of P. napi, evidenced by a prolonged development time and reduced larval growth rate, body mass, fat content, and phenoloxidase activity. Genotype by environment interactions (G × E) were present in several performance traits, indicating that Italian populations (1) respond more strongly to variation in host‐plant quality and (2) are more sensitive to poor food quality than German ones. This may reflect a cost of the rapid lifestyle found in Italian populations. Consequently, German populations may be more resilient against environmental perturbations and may perhaps even benefit from warmer temperatures, while Italian populations will likely suffer from the concomitantly reduced host‐plant quality. Our study thus exemplifies how investigating G × E may help to better understand the vulnerability of populations to climate change.     

Autumn larval cold tolerance does not predict the northern range limit of a widespread butterfly species

Climate change is driving range shifts, and a lack of cold tolerance is hypothesized to constrain insect range expansion at poleward latitudes. However, few, if any, studies have tested this hypothesis during autumn when organisms are subjected to sporadic low‐temperature exposure but may not have become cold‐tolerant yet. In this study, we integrated organismal thermal tolerance measures into species distribution models for larvae of the Giant Swallowtail butterfly, Papilio cresphontes (Lepidoptera: Papilionidae), living at the northern edge of its actively expanding range. Cold hardiness of field‐collected larvae was determined using three common metrics of cold‐induced physiological thresholds: the supercooling point, critical thermal minimum, and survival following cold exposure. P. cresphontes larvae were determined to be tolerant of chilling but generally die at temperatures below their SCP, suggesting they are chill‐tolerant or modestly freeze‐avoidant. Using this information, we examined the importance of low temperatures at a broad scale, by comparing species distribution models of P. cresphontes based only on environmental data derived from other sources to models that also included the cold tolerance parameters generated experimentally. Our modeling revealed that growing degree‐days and precipitation best predicted the distribution of P. cresphontes, while the cold tolerance variables did not explain much variation in habitat suitability. As such, the modeling results were consistent with our experimental results: Low temperatures in autumn are unlikely to limit the distribution of P. cresphontes. Understanding the factors that limit species distributions is key to predicting how climate change will drive species range shifts.     

Mitochondrial DNA D‐loop sequence analysis reveals high variation and multiple maternal origins of indigenous Tanzanian goat populations

The Small East African (SEA) goat are widely distributed in different agro‐ecological zones of Tanzania. We report the genetic diversity, maternal origin, and phylogenetic relationship among the 12 Tanzanian indigenous goat populations, namely Fipa, Songwe, Tanga, Pwani, Iringa, Newala, Lindi, Gogo, Pare, Maasai, Sukuma, and Ujiji, based on the mitochondrial DNA (mtDNA) D‐loop. High haplotype (H _d = 0.9619–0.9945) and nucleotide (π = 0.0120–0.0162) diversities were observed from a total of 389 haplotypes. The majority of the haplotypes (n = 334) belonged to Haplogroup A which was consistent with the global scenario on the genetic pattern of maternal origin of all goat breeds in the world. Haplogroup G comprised of 45 haplotypes drawn from all populations except the Ujiji goat population while Haplogroup B with 10 haplotypes was dominated by Ujiji goats (41%). Tanzanian goats shared four haplotypes with the Kenyan goats and two with goats from South Africa, Namibia, and Mozambique. There was no sharing of haplotypes observed between individuals from Tanzanian goat populations with individuals from North or West Africa. The indigenous goats in Tanzania have high genetic diversity defined by 389 haplotypes and multiple maternal origins of haplogroup A, B, and G. There is a lot of intermixing and high genetic variation within populations which represent an abundant resource for selective breeding in the different agro‐ecological regions of the country.     

Low base‐substitution mutation rate and predominance of insertion‐deletion events in the acidophilic bacterium Acidobacterium capsulatum

Analyses of spontaneous mutation have shown that total genome‐wide mutation rates are quantitatively similar for most prokaryotic organisms. However, this view is mainly based on organisms that grow best around neutral pH values (6.0–8.0). In particular, the whole‐genome mutation rate has not been determined for an acidophilic organism. Here, we have determined the genome‐wide rate of spontaneous mutation in the acidophilic Acidobacterium capsulatum using a direct and unbiased method: a mutation‐accumulation experiment followed by whole‐genome sequencing. Evaluation of 69 mutation accumulation lines of A. capsulatum after an average of ~2900 cell divisions yielded a base‐substitution mutation rate of 1.22 × 10⁻¹⁰ per site per generation or 4 × 10⁻⁴ per genome per generation, which is significantly lower than the consensus value (2.5−4.6 × 10⁻³) of mesothermophilic (~15–40°C) and neutrophilic (pH 6–8) prokaryotic organisms. However, the insertion‐deletion rate (0.43 × 10⁻¹⁰ per site per generation) is high relative to the base‐substitution mutation rate. Organisms with a similar effective population size and a similar expected effect of genetic drift should have similar mutation rates. Because selection operates on the total mutation rate, it is suggested that the relatively high insertion‐deletion rate may be balanced by a low base‐substitution rate in A. capsulatum, with selection operating on the total mutation rate.     

Remifentanil up‐regulates HIF1α expression to ameliorate hepatic ischaemia/reperfusion injury via the ZEB1/LIF axis

Ischaemia/reperfusion (I/R)‐induced hepatic injury is regarded as a main reason of hepatic failure after transplantation or lobectomy. The current study aimed to investigate how the opioid analgesic remifentanil treatment affects I/R‐induced hepatic injury and explore the possible mechanisms related to HIF1α. Initially, an I/R‐induced hepatic injury animal model was established in C57BL/6 mice, and an in vitro hypoxia‐reoxygenation model was constructed in NCTC‐1469 cells, followed by remifentanil treatment and HIF1α silencing treatment. The levels of blood glucose, lipids, alanine transaminase (ALT) and aspartate transaminase (AST) in mouse serum were measured using automatic chemistry analyser, while the viability and apoptosis of cells were detected using CCK8 assay and flow cytometry. Our results revealed that mice with I/R‐induced hepatic injury showed higher serum levels of blood glucose, lipids, ALT and AST and leukaemia inhibitory factor (LIF) expression, and lower HIF1α and ZEB1 expression (P < .05), which were reversed after remifentanil treatment (P < .05). Besides, HIF1α silencing increased the serum levels of blood glucose, lipids, ALT and AST (P < .05). Furthermore, hypoxia‐induced NCTC‐1469 cells exhibited decreased HIF1α and ZEB1 expression, reduced cell viability, as well as increased LIF expression and cell apoptosis (P < .05), which were reversed by remifentanil treatment (P < .05). Moreover, HIF1α silencing down‐regulated ZEB1 expression, decreased cell viability, and increased cell apoptosis (P < .05). ZEB1 was identified to bind to the promoter region of LIF and inhibit its expression. In summary, remifentanil protects against hepatic I/R injury through HIF1α and downstream effectors.     

Genetic structure and life history are key factors in species distribution models of spiny lobsters

AimWe incorporated genetic structure and life history phase in species distribution models (SDMs) constructed for a widespread spiny lobster, to reveal local adaptations specific to individual subspecies and predict future range shifts under the RCP 8.5 climate change scenario.LocationIndo‐West Pacific.MethodsMaxEnt was used to construct present‐day SDMs for the spiny lobster Panulirus homarus and individually for the three genetically distinct subspecies of which it comprises. SDMs incorporated both sea surface and benthic (seafloor) climate layers to recreate discrete influences of these habitats during the drifting larval and benthic juvenile and adult life history phases. Principle component analysis (PCA) was used to infer environmental variables to which individual subspecies were adapted. SDM projections of present‐day habitat suitability were compared with predictions for the year 2,100, under the RCP 8.5 climate change scenario.ResultsIn the PCA, salinity best explained P. h. megasculptus habitat suitability, compared with current velocity in P. h. rubellus and sea surface temperature in P. h. homarus. Drifting and benthic life history phases were adapted to different combinations of sea surface and benthic environmental variables considered. Highly suitable habitats for benthic phases were spatially enveloped within more extensive sea surface habitats suitable for drifting larvae. SDMs predicted that present‐day highly suitable habitats for P. homarus will decrease by the year 2,100.Main conclusionsIncorporating genetic structure in SDMs showed that individual spiny lobster subspecies had unique adaptations, which could not be resolved in species‐level models. The use of sea surface and benthic climate layers revealed the relative importance of environmental variables during drifting and benthic life history phases. SDMs that included genetic structure and life history were more informative in predictive models of climate change effects.     

Marine subsidy promotes spatial and dietary niche variation in an omnivore,the Keen’s mouse (Peromyscus keeni)

Marine‐derived resource subsidies can generate intrapopulation variation in the behaviors and diets of terrestrial consumers. How omnivores respond, given their multiple trophic interactions, is not well understood. We sampled mice (Peromyscus keeni) and their food sources at five sites on three islands of the Central Coast of British Columbia, Canada, to test predictions regarding variation in the spatial behavior and consumption of marine‐subsidized foods among individuals. About 50% of detections (n = 27 recaptures) occurred at traps closest to shoreline (25 m), with capture frequencies declining significantly inland (up to 200 m). Stable isotope signatures (δ ¹³C and δ ¹⁵N), particularly δ ¹⁵N, in plant foods, forest arthropod prey, and mouse feces were significantly enriched near shorelines compared with inland, while δ ¹³C patterns were more variable. Bayesian isotope mixing models applied to isotope values in mouse hair indicated that over one‐third (35–37%) of diet was comprised of beach‐dwelling arthropods, a marine‐derived food source. Males were more abundant near the shoreline than females and consumed more marine‐derived prey, regardless of reproductive status or availability of other food sources. Our results identify how multiple pathways of marine nutrient transfer can subsidize terrestrial omnivores and how subsets of recipient populations can show variation in spatial and dietary response.     

Parallel morphological evolution and habitat‐dependent sexual dimorphism in cave‐ vs. surface populations of the Asellus aquaticus (Crustacea: Isopoda: Asellidae) species complex

Studying parallel evolution (repeated, independent evolution of similar phenotypes in similar environments) is a powerful tool to understand environment‐dependent selective forces. Surface‐dwelling species that repeatedly and independently colonized caves provide unique models for such studies. The primarily surface‐dwelling Asellus aquaticus species complex is a good candidate to carry out such research, because it colonized several caves in Europe. By comparing 17 functional morphological traits between six cave and nine surface populations of the A. aquaticus species complex, we investigated population divergence in morphology and sexual dimorphism. We found habitat‐dependent population divergence in 10 out of 17 traits, likely reflecting habitat‐driven changes in selection acting on sensory systems, feeding, grooming, and antipredator mechanisms. Sexual dimorphism was present in 15 traits, explained by sexual selection acting on male traits important in male–male agonistic behavior or mate guarding and fecundity selection acting on female traits affecting offspring number and nursing. In eight traits, the degree of sexual dimorphism was habitat dependent. We conclude that cave‐related morphological changes are highly trait‐ and function‐specific and that the strength of sexual/fecundity selection strongly differs between cave and surface habitats. The considerable population variation within habitat type warrants further studies to reveal cave‐specific adaptations besides the parallel patterns.     

Phylogeography of sugar kelp: Northern ice‐age refugia in the Gulf of Alaska

Many Northeast (NE) Pacific fishes and invertebrates survived Pleistocene glaciations in northern refugia, but the extent that kelps survived in northern areas is uncertain. Here, we test the hypothesis that populations of sugar kelp (Saccharina latissima) persisted in the Gulf of Alaska during ice‐age maxima when the western margin of the Cordilleran ice sheet covered coastal areas around the NE Pacific Ocean. We estimated genetic diversities within and phylogeographical relationships among 14 populations along 2,800 km in the NE Pacific and Bering Sea with partial sequences of mitochondrial DNA 5′‐cytochrome oxidase subunit I (COI, bp = 624, n = 543), chloroplast DNA ribulose‐1,5‐bisphosphate carboxylase large subunit‐3′ (rbcL, bp = 735, n = 514), and 11 microsatellite loci. Concatenated sequences of rbcL and COI showed moderate levels of within‐population genetic diversity (mean h = 0.200) but substantial differences among populations (Φ_ST = 0.834, p < .0001). Microsatellites showed moderate levels of heterozygosity within populations (mean H _E = 0.391). Kelps in the same organellar lineage tended to cluster together, regardless of geographic origins, as indicated in a principal coordinate analysis (PCoA) of microsatellite genotypes. The PCoA also showed evidence of nuclear hybridizations between co‐occurring organellar lineages. Individual admixture plots with population clusters of K = 2, 6, and 9 showed increasing complexity with considerable historical admixture between some clusters. A time‐calibrated phylogeny placed divergences between rbcL‐COI lineages at 1.4 million years at most. The time frames of mutation in the rbcL‐COI lineages and microsatellite population clusters differed among locations. The existence of ancient lineages in the Gulf of Alaska, moderate levels of genetic diversity, and the absence of departures from neutrality are consistent with northern refugia during multiple Croll‐Milankovitch climate cycles in the Pleistocene Epoch.     

A temporal trophic shift from primary parasitism to facultative hyperparasitism during interspecific competition between two coevolved scelionid egg parasitoids

Understanding competition between scelionid parasitoids that exploit the same host may provide insight into strategies that allow coexistence on a shared resource. Competition studies typically focus on interactions between native and exotic parasitoids that do not share an evolutionary history; however, coevolved parasitoids may be more likely to demonstrate strategies to avoid or exploit a shared resource. We examined intrinsic and extrinsic competition between Asian Trissolcus japonicus (Ashmead) and T. cultratus (Mayr) (Hymenoptera: Scelionidae) associated with Halyomorpha halys (Stål) (Hemiptera: Pentatomidae) that share an evolutionary history. Interspecific interactions were assessed by providing parasitized egg masses to each species at various intervals post‐parasitism, and measuring host acceptance, developmental suitability, and guarding behaviour. Trissolcus japonicus showed high acceptance of parasitized hosts up to 72 h following oviposition by T. cultratus, despite a very poor developmental outcome. In contrast, T. cultratus generally avoided ovipositing in H. halys eggs containing T. japonicus early‐instar larvae but did not avoid parasitizing H. halys that contained eggs and third instar larvae. The adaptive value of this behaviour was supported by developmental outcome: T. cultratus outcompeted T. japonicus eggs but not early‐instar larvae, and a trophic shift occurred wherein T. cultratus developed as a facultative hyperparasitoid on third instar T. japonicus larvae. Trissolcus japonicus guarded egg masses 8–12× longer and displayed more aggressive interactions than T. cultratus, suggesting T. japonicus is the superior extrinsic competitor. Development as a facultative hyperparasitoid provided a competitive niche for Asian T. cultratus and confirms its instrinsic competitive superiority. This also occurs in a biologically distinct European population of T. cultratus, suggesting that facultative hyperparasitism as a competitive strategy is retained in geographically separated populations that have not coevolved with H. halys or T. japonicus.     

Patterns of testosterone in male white‐tailed deer (Odocoileus virginianus): Seasonal and lifetime variation

Testosterone is strongly associated with the annual development of antlers in cervids, but endocrine research on wild, freely breeding ungulates is often done without repeated capture of known‐aged individuals. As a result, our knowledge on how testosterone fluctuates over the course of a lifetime and variation in lifetime patterns among individuals is limited. We investigated patterns of testosterone in a freely breeding population of white‐tailed deer (Odocoileus virginianus) in Alabama, USA, that breeds in January. Testosterone peaked during the height of the breeding season, despite this period occurring approximately 2 months later than in most temperate‐region white‐tailed deer populations. Age‐related differences in testosterone were only prevalent during the breeding season, with bucks ≥3.5 years old having greater testosterone (853 ng/dl ± 96 SE; p = 0.012) than bucks 1.5–2.5 years old (364 ng/dl ± 100 SE). Additionally, an individual''s testosterone level as a yearling was not positively associated with their lifetime maximum testosterone level (p = 0.583), and an individual''s mean testosterone level was positively associated with lifetime testosterone variation (p < 0.001). To our knowledge, our study is one of the first to assess how testosterone early in life might relate to individual testosterone later in life. We believe these data provide insight into lifetime hormonal patterns in cervids, and that these patterns may indicate intraspecific variation of lifetime reproductive strategies.     

Genetic variation and reproductive patterns in wetland mosses suggest efficient initial colonization of disturbed sites

To understand colonization processes, it is critical to fully assess the role of dispersal in shaping biogeographical patterns at the gene, individual, population, and community levels. We test two alternative hypotheses (H I and H II) for the colonization of disturbed sites by clonal plants, by analyzing intraspecific genetic variation in one and reproductive traits in two typical fen mosses with separate sexes and intermittent spore dispersal, comparing disturbed, early‐succession (limed) fens and late‐successional rich fens. H I suggests initial colonization of disturbed sites by diverse genotypes of which fewer remain in late‐successional fens and an initially balanced sex ratio that develops into a possibly skewed population sex ratio. H II suggests initial colonization by few genotypes and gradual accumulation of additional genotypes and an initially skewed sex ratio that alters into the species‐specific sex ratio, during succession. Under both scenarios, we expect enhanced sexual reproduction in late‐successional fens due to resource gains and decreased intermate distances when clones expand. We show that the intraspecific genetic diversity, assessed by two molecular markers, in Scorpidium cossonii was higher and the genetic variation among sites was smaller in disturbed than late‐successional rich fens. Sex ratio was balanced in S. cossonii and Campylium stellatum in disturbed fens and skewed in C. stellatum in late‐successional fens, thus supporting H I. In line with our prediction, sex expression incidence was higher in, and sporophytes were confined to, late‐succession compared to disturbed rich fens. Late‐successional S. cossonii sites had more within‐site patches with two or more genotypes, and both species displayed higher sex expression levels in late‐successional than in disturbed sites. We conclude that diverse genotypes and both sexes disperse efficiently to, and successfully colonize new sites, while patterns of genetic variation and sexual reproduction in late‐successional rich fens are gradually shaped by local conditions and interactions over extended time periods.     

Female extra‐pair behavior is not associated with reduced paternal care in Thorn‐tailed Rayadito

Extra‐pair behavior is present in 76% of socially monogamous bird species with biparental care. This behavior may produce costs to females related to a reduction in paternal care. We estimated the percentage of extra‐pair offspring and quantified paternal care in 44 nests of Thorn‐tailed Rayadito (Aphrastura spinicauda) to assess whether males reduce their parental care when females obtain extra‐pair fertilizations. We used data from a sub‐Antarctic population of Rayadito located on Navarino Island (55°4′S, 67°40′W), southern Chile. We found no statistical support for a relationship between variation in paternal care and the percentage of extra‐pair offspring. We discuss how the inability of breeding males to assess their genetic paternity and potential restrictions on behavioral flexibility may explain this result. Additionally, if paternal care is subjected to sexual selection, this could limit a facultative response to female extra‐pair behavior by males. Finally, it is possible that a reduction in paternal care might not have evolved in this particular locality given the low frequency of extra‐pair paternity in our study population.     

Evolutionary innovations in Antarctic brittle stars linked to glacial refugia

The drivers behind evolutionary innovations such as contrasting life histories and morphological change are central questions of evolutionary biology. However, the environmental and ecological contexts linked to evolutionary innovations are generally unclear. During the Pleistocene glacial cycles, grounded ice sheets expanded across the Southern Ocean continental shelf. Limited ice‐free areas remained, and fauna were isolated from other refugial populations. Survival in Southern Ocean refugia could present opportunities for ecological adaptation and evolutionary innovation. Here, we reconstructed the phylogeographic patterns of circum‐Antarctic brittle stars Ophionotus victoriae and O. hexactis with contrasting life histories (broadcasting vs brooding) and morphology (5 vs 6 arms). We examined the evolutionary relationship between the two species using cytochrome c oxidase subunit I (COI) data. COI data suggested that O. victoriae is a single species (rather than a species complex) and is closely related to O. hexactis (a separate species). Since their recent divergence in the mid‐Pleistocene, O. victoriae and O. hexactis likely persisted differently throughout glacial maxima, in deep‐sea and Antarctic island refugia, respectively. Genetic connectivity, within and between the Antarctic continental shelf and islands, was also observed and could be linked to the Antarctic Circumpolar Current and local oceanographic regimes. Signatures of a probable seascape corridor linking connectivity between the Scotia Sea and Prydz Bay are also highlighted. We suggest that survival in Antarctic island refugia was associated with increase in arm number and a switch from broadcast spawning to brooding in O. hexactis, and propose that it could be linked to environmental changes (such as salinity) associated with intensified interglacial‐glacial cycles.     

Dynamics of NK,CD8 and Tfh cell mediated the production of cytokines and antiviral antibodies in Chinese patients with moderate COVID‐19

Recent studies have demonstrated a marked decrease in peripheral lymphocyte levels in patients with coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Few studies have focused on the changes of NK, T‐ and B‐cell subsets, inflammatory cytokines and virus‐specific antibodies in patients with moderate COVID‐19. A total of 11 RT‐PCR‐confirmed convalescent patients with COVID‐19 and 11 patients with non‐SARS‐CoV‐2 pneumonia (control patients) were enrolled in this study. NK, CD8⁺ T, CD4⁺ T, Tfh‐like and B‐cell subsets were analysed using flow cytometry. Cytokines and SARS‐CoV‐2‐specific antibodies were analysed using an electrochemiluminescence immunoassay. NK cell counts were significantly higher in patients with COVID‐19 than in control patients (P = 0.017). Effector memory CD8⁺ T‐cell counts significantly increased in patients with COVID‐19 during a convalescent period of 1 week (P = 0.041). TIM‐3⁺ Tfh‐like cell and CD226⁺ Tfh‐like cell counts significantly increased (P = 0.027) and decreased (P = 0.022), respectively, during the same period. Moreover, ICOS⁺ Tfh‐like cell counts tended to decrease (P = 0.074). No abnormal increase in cytokine levels was observed. The high expression of NK cells is important in innate immune response against SARS‐CoV‐2. The increase in effector memory CD8⁺ T‐cell counts, the up‐regulation of inhibitory molecules and the down‐regulation of active molecules on CD4⁺ T cells and Tfh‐like cells in patients with COVID‐19 would benefit the maintenance of balanced cellular and humoural immune responses, may prevent the development of severe cases and contribute to the recovery of patients with COVID‐19.     

Newly designed Protein Transduction Domain (PTD)‐mediated BMP‐7 is a potential therapeutic for peritoneal fibrosis

While the bone morphogenetic protein‐7 (BMP‐7) is a well‐known therapeutic growth factor reverting many fibrotic diseases, including peritoneal fibrosis by peritoneal dialysis (PD), soluble growth factors are largely limited in clinical applications owing to their short half‐life in clinical settings. Recently, we developed a novel drug delivery model using protein transduction domains (PTD) overcoming limitation of soluble recombinant proteins, including bone morphogenetic protein‐7 (BMP‐7). This study aims at evaluating the therapeutic effects of PTD‐BMP‐7 consisted of PTD and full‐length BMP‐7 on epithelial‐mesenchymal transition (EMT)‐related fibrosis. Human peritoneal mesothelial cells (HPMCs) were then treated with TGF‐β1 or TGF‐β1 + PTD‐BMP‐7. Peritoneal dialysis (PD) catheters were inserted into Sprague‐Dawley rats, and these rats were infused intra‐peritoneally with saline, peritoneal dialysis fluid (PDF) or PDF + PTD‐BMP‐7. In vitro, TGF‐β1 treatment significantly increased fibronectin, type I collagen, α‐SMA and Snail expression, while reducing E‐cadherin expression in HPMCs (P < .001). PTD‐BMP‐7 treatment ameliorated TGF‐β1‐induced fibronectin, type I collagen, α‐SMA and Snail expression, and restored E‐cadherin expression in HPMCs (P < .001). In vivo, the expressions of EMT‐related molecules and the thickness of the sub‐mesothelial layer were significantly increased in the peritoneum of rats treated with PDF, and these changes were significantly abrogated by the intra‐peritoneal administration of PTD‐BMP‐7. PTD‐BMP‐7 treatment significantly inhibited the progression of established PD fibrosis. These findings suggest that PTD‐BMP‐7, as a prodrug of BMP‐7, can be an effective therapeutic agent for peritoneal fibrosis in PD patients.