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Exhaustion of cytotoxic effector natural killer (NK) and CD8 + T cells have important functions in the establishment of persistent viral infections, but how exhaustion is induced during chronic hepatitis C virus (HCV) infection remains poorly defined. Here we show, using the humanized C/O Tg mice permissive for persistent HCV infection, that NK and CD8 + T cells become sequentially exhausted shortly after their transient hepatic infiltration and activation in acute HCV infection. HCV infection upregulates Qa-1 expression in hepatocytes, which ligates NKG2A to induce NK cell exhaustion. Antibodies targeting NKG2A or Qa-1 prevents NK exhaustion and promotes NK-dependent HCV clearance. Moreover, reactivated NK cells provide sufficient IFN-γ that helps rejuvenate polyclonal HCV CD8 + T cell response and clearance of HCV. Our data thus show that NKG2A serves as a critical checkpoint for HCV-induced NK exhaustion, and that NKG2A blockade sequentially boosts interdependent NK and CD8 + T cell functions to prevent persistent HCV infection. Immune cells may become less responsive, or ‘exhausted’, upon chronic viral infection, but the underlying mechanism and crosstalk are still unclear. Here the authors show that, upon chronic hepatitis C virus (HCV) infection, natural killer cell exhaustion is induced by NKG2A signalling to instruct downstream exhaustion of CD8 + T cells and HCV persistence.

A major goal of seasonal biology is to understand how selection on phenology and the physiological niche interact. In oviparous species, fitness variation across the growing season suggests that phenological shifts will alter selective environments experienced by embryos. We hypothesize that physiology could become co‐adapted with phenology; such that embryos perform better in the environmental conditions they are adapted to compared to embryos adapted to other environments (temporal matching). Here, we tested for temporal matching to seasonal changes in the environmental temperatures with toad‐headed lizard, Phrynocephalus przewalskii, which inhabits the temperate desert steppe of China. We used a split‐clutch reciprocal experiment, by incubating eggs from early‐ and late‐breeding females at rising and falling temperature regimes, respectively, to separate the influence of intrinsic (genetic and parental) vs. extrinsic factors (developmental plasticity or acclimatization) on the performance and fitness of offspring. Eggs from early‐breeding females were with higher quality than those from late‐breeding females, likely due to better maternal provisioning. Offspring from early‐breeding females had higher selected body temperatures and metabolic rates than those from late‐breeding females. Falling temperatures that may indicate the end of the growing season, reduced incubation duration and increased metabolic rates for both early and late eggs, compared to rising temperatures. Late hatchlings had higher growth rates when incubated at falling compared to rising temperatures, while growth rates of early hatchlings were not sensitive to incubation temperature. Thus, growth and survival rates of late embryos were similar to early embryos under falling temperatures, despite early embryos being of generally higher quality. Overall, our study confirms that “early is higher quality.” Intrinsic factors dominate offspring performance and fitness, with a general advantage for early embryos throughout the season. We found some support for temporal matching, demonstrating that late embryos with lower quality have physiological strategies that are specialized to late‐season environments, allowing them to attain similar fitness in late‐season environments to that of early embryos. A plain language summary is available for this article. Plain Language Summary

The fitness consequence of maternal nest‐site choice has attracted increasing scientific attention, but field studies identifying the long‐term effects of nest‐site choice on offspring survival and reproductive success are still rare in vertebrates. To investigate the consequences of nest‐site choice in lizards, we quantified the thermal and hydric conditions of nest sites that were chosen by female toad‐headed agama (Phrynocephalus przewalskii) in the desert steppe of northern China. We also determined the effect of nest‐site choice on embryonic development and survival and on offspring growth, survival and maturity by comparing the embryos and offspring from maternally and randomly chosen nest sites. We found that female toad‐headed agama chose warm and moist nest sites that improved the developmental rate and survivorship of embryos and promoted the post‐hatching growth, sexual maturity, reproduction and fitness of offspring, thereby improving their reproductive success. Such studies on short‐lived lizards across multiple stages of embryonic and postembryonic ontogeny are critical for fully understanding the fitness consequences of nest‐site choice. A plain language summary is available for this article. Plain Language Summary

While the effects of incubation environment on embryonic development and offspring traits have been extensively studied in oviparous vertebrates, studies into how genetic inheritance (population origin), maternal effects, and incubation environment interact to produce varying phenotypes, are rare. To elucidate the interactive role of those three factors during incubation in shaping offspring phenotypes through hydric conditions, we conducted a fully factorial experiment [arid and semiarid populations × maternal dry and wet treatments (MDT and MWT) × embryonic dry and wet treatments (EDT and EWT)] with a desert-dwelling lacertid lizard (Eremias argus). Female lizards in dry conditions produced larger clutch sizes but smaller eggs. The incubation period and hatching success were significantly affected by embryonic but not by maternal moisture treatments. Eggs in the EDT hatched later than those in the EWT in both arid and semiarid populations. Hatching success was lower in EDT than in EWT in the semiarid population, but not in the arid population. Hatchlings from the EDT had a slower post-hatch increase in body mass than those from the EWT. EDT would decrease the survival rates of hatchlings in the semiarid population only. In addition, structural equation models revealed that population had a stronger effect on embryonic and offspring survival than maternal and embryonic moisture. Our study demonstrates locally adaptive strategies of drought resistance at multiple life-history stages in lizard populations from diverse hydric habitats and highlights the importance of genetic factors in determining embryonic drought resistance in oviparous lizards.

Species distribution models (SDMs) across past, present, and future timelines provide insights into the current distribution of these species and their reaction to climate change. Specifically, if a species is threatened or not well‐known, the information may be critical to understand that species. In this study, we computed SDMs for Orientocoluber spinalis, a monotypic snake genus found in central and northeast Asia, across the past (last interglacial, last glacial maximum, and mid‐Holocene), present, and future (2070s). The goal of the study was to understand the shifts in distribution across time, and the climatic factors primarily affecting the distribution of the species. We found the suitable habitat of O. spinalis to be persistently located in cold‐dry winter and hot summer climatic areas where annual mean temperature, isothermality, and annual mean precipitation were important for suitable habitat conditions. Since the last glacial maximum, the suitable habitat of the species has consistently shifted northward. Despite the increase in suitable habitat, the rapid alterations in weather regimes because of climate change in the near future are likely to greatly threaten the southern populations of O. spinalis, especially in South Korea and China. To cope with such potential future threats, understanding the ecological requirements of the species and developing conservation plans are urgently needed. We predicted the habitat suitability of Orientocoluber spinalis, a monotypic snake genus found in central and northeast Asia, across past, present, and future timelines, providing insights on the current distribution and their reaction to climate change.

With limited resources and efforts, assessing species' vulnerabilities across various geographic regions before the conservation practice is essential for biodiversity conservation in the context of climate change. One pressing challenge has been establishing natural temperature‐manipulated research systems across latitudes. To address this challenge, an innovative infrastructure is developed named the semi‐natural climate chambers across latitudes (SCCAL), consisting of semi‐natural climate chambers at three latitudes, spanning 27° and 3393 km from tropical to temperate regions. Each latitude features eight medium‐sized patches for temperature manipulation, organisms rearing, and ecological experiments. Independent of external water and electricity supplies, the SCCAL allows to simulate thermal environments under different climate change scenarios with natural soil moisture. Ecological experiments with Grass lizards successfully are conducted, demonstrating that the SCCAL effectively supports species rearing, responses determining, and the vulnerability assessing. The widespread adoption or development of similar infrastructures is encouraged, which can facilitate the assessment of latitudinal animal vulnerabilities under climate change. Assessing species' vulnerabilities across geographical gradients is essential for biodiversity conservation under climate change. To address this challenge, the semi‐natural climate chamber across latitudes (SCCAL) is developed, a validated system capable of simulating thermal environments for ecological experiments without reliance on water or electricity. The widespread adoption of SCCAL is advocated to facilitate ecological research on climate change.

Summary Whether maternal effects are adaptive or not has been a long‐standing topic of discussion in evolutionary ecology. The effects of maternal diet on offspring have been addressed by several studies on diverse organisms, but results are typically conflicting or inconclusive. In this study, we conducted food manipulation experiments with a factorial design (high and low maternal food conditions × high and low offspring food conditions) in a viviparous lacertid lizard (Eremias multiocellata) to test four competing hypotheses on the evolutionary significance of maternal effects: environmental matching hypothesis, low‐food compensation hypothesis, low‐food pathology hypothesis and no‐compensation hypothesis. We found that offspring under the maternal low‐food treatment had higher growth and survival rates than those under the maternal high‐food treatment, supporting the low‐food compensation hypothesis rather than the environmental matching hypothesis, which has been widely accepted as an explanation for the adaptive significance of maternal effects. Our study highlights the importance of testing multiple competing hypotheses that involve both adaptive and non‐adaptive explanations when studying the evolutionary significance of phenotypic plasticity. A lay summary is available for this article. Lay Summary

Compared with neostigmine, sugammadex promotes faster neuromuscular recovery, but its impact on diaphragmatic function and respiratory recovery in the morbidly obese cohort, and the mechanism underlying its reduction of postoperative pulmonary complications remain unclear. This study aims to compare the effects of sugammadex and neostigmine on diaphragmatic function and respiratory recovery in morbidly obese patients after surgery, and to investigate the role of diaphragmatic function in the reduction of sugammadex-associated postoperative pulmonary complications. For neuromuscular blockade reversal, 104 morbidly obese patients with moderate neuromuscular block (train-of-four count = 2, ratio <0.9) were randomly assigned to receive either neostigmine (50 μg kg-1+atropine 20 μg kg-1, n=51) or sugammadex (2 mg kg-1, n=53). Measurements of diaphragmatic excursion (DE) and thickening fraction (TF) were taken during deep and quiet breathing at T0 (baseline), T1 (10 min), and T2 (30 min) after extubation. The primary outcome measure was the change in deep breathing diaphragmatic excursion (ΔDE ) from baseline at T2. The secondary outcome measures included ΔDE , ΔDE , and ΔTF at T1; ΔDE and ΔTF at T2; postoperative oxygenation index; number of respiratory reminders; and the frequency of postoperative pulmonary complications. At T2, the ΔDE was smaller in the sugammadex group compared with the neostigmine group (0.05 cm vs. 0.28 cm; < 0.001). At T1, the ΔDE , ΔDE , and ΔTF all differed significantly between groups, as did the ΔTF at T2 (all ≤ 0.001). The sugammadex group also demonstrated a higher oxygenation index ( =0.004) and a lower incidence of postoperative pulmonary complications ( =0.007). In morbid obesity, sugammadex promotes faster diaphragmatic recovery and improves respiratory outcomes compared with neostigmine and is associated with a lower incidence of postoperative pulmonary complications.

Estrogen replacement therapy (ERT) is a common treatment method for menopausal syndrome; however, its therapeutic value for the treatment of neurological diseases is still unclear. Epidemiological studies were performed, and the effect of postmenopausal ERT on treating neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD), was summarized through a meta-analysis. Twenty-one articles were selected using a systematic searching of the contents listed on PubMed and Web of Science before June 1, 2019. Epidemiological studies were extracted, and relevant research data were obtained from the original articles based on the predefined inclusion criteria and data screening principles. The Comprehensive Meta-Analysis Version 2 software was used to pool effective size, test heterogeneity, conduct meta-regression and subgroup analysis, and to calculate publication bias. Our results showed that ERT significantly decreased the risk of onset and/or development of AD [odds ratio (OR): 0.672; 95% CI: 0.581-0.779; < 0.001] and PD (OR: 0.470; 95% CI: 0.368-0.600; < 0.001) compared with the control group. A subgroup and meta-regression analysis showed that study design and measure of effect were the source of heterogeneity. Age, sample size, hormone therapy ascertainment, duration of the treatment, or route of administration did not play a significant role in affecting the outcome of the meta-analysis. We presented evidence here to support the use of estrogen therapy for the treatment of AD and PD.

Background Understanding the geographical distribution of a species is a key component of studying its ecology, evolution, and conservation. Although Schlegel’s Japanese gecko ( Gekko japonicus ) is widely distributed in Northeast Asia, its distribution has not been studied in detail. We predicted the present and future distribution of G. japonicus across China, Japan, and Korea based on 19 climatic and 5 environmental variables using the maximum entropy (MaxEnt) species distribution model. Results Present time major suitable habitats for G. japonicus , having greater than 0.55 probability of presence (threshold based on the average predicted probability of the presence records), are located at coastal and inland cities of China; western, southern, and northern coasts of Kyushu and Honshu in Japan; and southern coastal cities of Korea. Japan contained 69.3% of the suitable habitats, followed by China (27.1%) and Korea (4.2%). Temperature seasonality (66.5% of permutation importance) was the most important predictor of the distribution. Future distributions according to two climate change scenarios predicted that by 2070, and overall suitable habitats would decrease compared to the present habitats by 18.4% (scenario RCP 4.5) and 10.4% (scenario RCP 8.5). In contrast to these overall trends, range expansions are expected in inland areas of China and southern parts of Korea. Conclusions Suitable habitats predicted for G. japonicus are currently located in coastal cities of Japan, China, and Korea, as well as in isolated patches of inland China. Due to climate change, suitable habitats are expected to shrink along coastlines, particularly at the coastal-edge of climate change zones. Overall, our results provide essential distribution range information for future ecological studies of G. japonicus across its distribution range.