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Life history theory assumes there are trade-offs between competing functions such as reproduction and immunity. Although well studied in birds, studies of the trade-offs between reproduction and immunity in small mammals are scarce. Here we examined whether reduced immunity is a consequence of reproductive effort in lactating Brandt's voles (Lasiopodomys brandtii). Specifically, we tested the effects of lactation on immune function (Experiment I). The results showed that food intake and resting metabolic rate (RMR) were higher in lactating voles (6≤ litter size ≤8) than that in non-reproductive voles. Contrary to our expectation, lactating voles also had higher levels of serum total Immunoglobulin G (IgG) and anti-keyhole limpet hemocyanin (KLH) IgG and no change in phytohemagglutinin (PHA) response and anti-KLH Immunoglobulin M (IgM) compared with non-reproductive voles, suggesting improved rather than reduced immune function. To further test the effect of differences in reproductive investment on immunity, we compared the responses between natural large (n≥8) and small litter size (n≤6) (Experiment II) and manipulated large (11-13) and small litter size (2-3) (Experiment III). During peak lactation, acquired immunity (PHA response, anti-KLH IgG and anti-KLH IgM) was not significantly different between voles raising large or small litters in both experiments, despite the measured difference in reproductive investment (greater litter size, litter mass, RMR and food intake in the voles raising larger litters). Total IgG was higher in voles with natural large litter size than those with natural small litter size, but decreased in the enlarged litter size group compared with control and reduced group. Our results showed that immune function is not suppressed to compensate the high energy demands during lactation in Brandt's voles and contrasting the situation in birds, is unlikely to be an important aspect mediating the trade-off between reproduction and survival.

Oxidative stress is a potential proximal physiological cost of reproduction. Detecting this cost may be performed in several different ways – manipulating reproductive status, correlating natural variations in effort to oxidative stress or manipulating reproductive effort. Here, we manipulated reproductive status and studied oxidative stress due to natural and experimental variation in reproductive effort in Brandt's voles (Lasiopodomys brandtii), using a variety of markers and tissues. We measured markers of oxidative stress in lactating (raising 6 to 8 offspring) and non‐reproductive voles (Experiment I) and found that a marker of oxidative protection [serum total‐superoxide dismutase (SOD) activity] was reduced, and a marker of oxidative damage (protein carbonyls) was increased, in the serum, in lactating compared with non‐reproductive voles. However, protein carbonyls in the liver were lower in lactating compared with non‐reproductive voles, consistent with increased liver SOD activity. Lipid damage [malonaldehyde (MDA)] in both serum and liver was unrelated to reproductive status. We compared these markers of oxidative stress between natural large (n ≥ 9) and small litter sizes (n ≤ 5; Experiment II), and between manipulated large (11–13) and small litter sizes (2–3; Experiment III) and found that liver MDA and SOD activity was higher in voles with natural large compared with natural small litter sizes, but there were no differences in other markers. There was no effect of litter size on all measures when it was experimentally manipulated. The effects of reproductive status on oxidative stress were critically dependent on the exact markers and tissues used. The effects of natural variation in reproductive effort suggested that there might be an oxidative stress cost associated with large litter sizes, but this effect was not replicated in the experimentally manipulated litters.

Brandt's voles have an annual cycle of body weight and adiposity. These changes can be induced in the laboratory by manipulation of photoperiod. In the present study, male captive-bred Brandt's voles aged 35 days were acclimated to a short day (SD) photoperiod (8L:16D) for 70 days. A subgroup of individuals (n=16) were implanted with transmitters to monitor physical activity and body temperature. They were then randomly allocated into long day (LD=16L:8D) (n=19, 8 with transmitters) and SD (n=18, 8 with transmitters) groups for an additional 70 days. We monitored aspects of energy balance, glucose and insulin tolerance (GTT and ITT), body composition and organ fat content after exposure to the different photoperiods. LD voles increased in weight for 35 days and then re-established stability at a higher level. At the end of the experiment LD-exposed voles had greater white adipose tissue mass than SD voles (P=0.003). During weight gain they did not differ in their food intake or digestive efficiency; however, daily energy expenditure was significantly reduced in the LD compared with SD animals (ANCOVA, P<0.05) and there was a trend to reduced resting metabolic rate RMR (P=0.075). Physical activity levels were unchanged. Despite different levels of fat storage, the GTT and ITT responses of SD and LD voles were not significantly different, and these traits were not correlated to body fatness. Hence, the photoperiod-induced obesity was independent on disruptions to glucose homeostasis, indicating a potential adaptive decoupling of these states in evolutionary time. Fat content in both the liver and muscle showed no significant difference between LD and SD animals. How voles overcome the common negative aspects of fat storage might make them a useful model for understanding the phenomenon of ‘healthy obesity’.

Previous studies at 21 °C and 5 °C suggest that in Swiss mice sustained energy intake (SusEI) and reproductive performance are constrained by the mammary capacity to produce milk. We aimed to establish if this constraint also applied at higher ambient temperature (30 °C). Female Swiss mice lactating at 30 °C had lower asymptotic food intake and weaned lighter litters than those at 21 °C. Resting metabolic rate, daily energy expenditure, milk energy output and suckling time were all lower at 30 °C. In a second experiment we gave mice at 30 °C either 6 or 9 pups to raise. Female performance was independent of litter size, indicating that it is probably not controlled by pup demands. In a third experiment we exposed only the mother, or only the offspring to the elevated temperature. In this case the performance of the mother was only reduced when she was exposed and not when her pups were exposed, showing that the high temperature directly constrains female performance. These data suggest that at 30 °C SusEI and reproductive performance are likely constrained by the capacity of females to dissipate body heat and not indirectly via pup demands. Constraints seem to change with ambient temperature in this strain of mouse.

Background：Limb-salvage surgery is the standard procedure for the treatment of appendicular osteosarcoma.Precise resection is the trend in limb-salvage surgery.The aim of this study was to evaluate a large series of cases to identify the histological relationship between the tumor and marrow and determine the intramedullary transition type and width from the tumor to normal marrow in patients with osteosarcoma after neoadjuvant chemotherapy.Methods：One hundred and six osteosarcoma specimens were evaluated.The tissue specimens were sectioned through the coronal axis by an electronic saw.The tissue was immersed in formalin solution for fixation and subsequently decalcified.The interface between the tumor and normal bone marrow was grossly determined and submitted for microscopic evaluation to detect the relationship between the tumor and bone marrow and identify the transition type and width.All histological slides were examined by experienced orthopedic pathologists.Results：Histologically,the interface between the tumor and normal bone marrow was classified into two patterns：＂clear＂ and ＂infiltrated.＂The clear pattern,characterized by a clear boundary between the tumor and marrow,was identified in sixty cases （56.6%）.A subtype of the clear type,characterized by fibrous bands between the tumor and marrow,was found in 13 cases （12.3%）.The infiltrated pattern,characterized by a boundary with tumor cell clusters embedded in the marrow,was found in 46 cases （43.4%）.The infiltrating depth varied from 1 to 4 mm （mean,2.6 ＋ 0.7 mm）.No tumor cells were observed in the normal bone marrow areas next to the interface.Conclusions：The transition from osteosarcoma tissue to bone marrow after neoadjuvant chemotherapy can be divided into two histological patterns：clear and infiltrated.The greatest infiltration width was 4 mm from tumor to normal marrow in this study.This depth should be considered in the presurgical plan.

Background Gross target volume of primary tumor (GTV‐P) is very important for the prognosis prediction of patients with nasopharyngeal carcinoma (NPC), but it is unknown whether the same is true for locally advanced NPC patients treated with intensity‐modulated radiotherapy (IMRT). This study aimed to clarify the prognostic value of tumor volume for patient with locally advanced NPC receiving IMRT and to find a suitable cut‐off value of GTV‐P for prognosis prediction. Methods Clinical data of 358 patients with locally advanced NPC who received IMRT were reviewed. Receiver operating characteristic (ROC) curves were used to identify the cut‐off values of GTV‐P for the prediction of different endpoints [overall survival (OS), local relapse‐free survival (LRFS), distant metastasis‐free survival (DMFS), and disease‐free survival (DFS)] and to test the prognostic value of GTV‐P when compared with that of the American Joint Committee on Cancer T staging system. Results The 358 patients with locally advanced NPC were divided into two groups by the cut‐off value of GTV‐P as determined using ROC curves: 219 (61.2%) patients with GTV‐P ≤46.4 mL and 139 (38.8%) with GTV‐P >46.4 mL. The 3‐year OS, LRFS, DMFS, and DFS rates were all higher in patients with GTV‐P ≤46.4 mL than in those with GTV‐P > 46.4 mL (all P < 0.05). Multivariate analysis indicated that GTV‐P >46.4 mL was an independent unfavorable prognostic factor for patient survival. The ROC curve verified that the predictive ability of GTV‐P was superior to that of T category (P < 0.001). The cut‐off values of GTV‐P for the prediction of OS, LRFS, DMFS, and DFS were 46.4, 57.9, 75.4 and 46.4 mL, respectively. Conclusion In patients with locally advanced NPC, GTV‐P >46.4 mL is an independent unfavorable prognostic indicator for survival after IMRT, with a prognostic value superior to that of T category.

Macrophages play an important role in the progression of sporadic acute type A aortic dissection (ATAAD). The aim of this study was to characterize the cellular heterogeneity of macrophages in ATAAD tissues by scRNA-seq. Ascending aortic wall tissue from six ATAAD patients and three heart transplant donors was assessed by scRNA-seq and then analyzed and validated by various bioinformatic algorithms and histopathology experiments. The results revealed that the proportion of macrophages in ATAAD tissues (24.51%) was significantly higher than that in normal tissues (13.69%). Among the six macrophage subclusters, pro-inflammatory macrophages accounted for 14.96% of macrophages in the AD group and 0.18% in the normal group. Chemokine- and inflammation-related genes (CCL2, CCL20, S100A8, and S100A9) were expressed more intensively in macrophages in ATAAD tissue than in those in normal tissue. Additionally, intercellular communication analysis and transcription factor analysis indicated the activation of inflammation and degradation of the extracellular matrix in ATAAD tissue. Finally, immunohistochemistry, immunofluorescence, and Western blot experiments confirmed the overexpression of macrophage marker genes (CD68 and CD163) and matrix metalloproteinases (MMP9 and MMP2) in ATAAD tissue. Collectively, our study provides a preliminary evaluation of the role of macrophages in ATAAD, and the results could aid in the development of therapeutic options in the future.

Whether rubber plantations have the role of water pumps in tropical Southeast Asia is under active debate. Fifteen years (1994–2008) of paired catchments water observation data and one year paired eddy covariance water flux data in primary tropical rain forest and tropical rubber plantation was used to clarify how rubber plantation affects local water resources of Xishuangbanna, China. Both catchment water observations and direct eddy covariance estimates indicates that more water was evapotranspired from rubber plantation (1137 mm based on catchment water balance, 1125 mm based on eddy covariance) than from the rain forest (969 mm based on catchment water balance, 927 mm based on eddy covariance). Soil water storage during the rainy season is not sufficient to maintain such high evapotranspiration rates, resulting in zero flow and water shortages during the dry season in the rubber plantation. Therefore, this study supports the idea that rubber plantations act as water pumps as suggested by local inhabitants. Key Points Two independent methods give the same results More water was evapotranspirated by rubber plantation than rain forest Rubber plantation do act as water pumps

To the Editor： A 35-year-old Chinese woman was admitted to our hospital complaining of a 1-year history of bilateral temporal chronic intermittent moderate headache which used to be alleviated by ibuprofen tablets or rest and had increased in intensity in the past 1 month. The patient also presented with the slow development of visual deficit. In January 2012, the patient presented with polyuria and polydipsia suggestive of central diabetes insipidus. Endocrine studies showed no clinically significant results.

The regrowth of tropical secondary forests and plantations can not offset the carbon release caused by tropical deforestation, consequently determining net carbon losses on tropical lands. However, large uncertainties remain in relation to this assumption. Here, we used a biometric method to estimate the net dry matter production and net ecosystem production in a rubber forest, the most widespread plantation type in tropical Southeast Asia. According to biometric estimates made during the study, the ecosystem was a carbon sink (790 gC m-2 yr-1). Net ecosystem carbon fluxes were measured by the eddy covariance method. The carbon budget estimated using the FluxNet procedure (904 gC m-2 yr-1) was closer to the biometric estimates in comparison to a method based on data measured during neutral atmospheric conditions. Overall, when considering the whole life cycle, including deforestation of the prior-existing tropical forest, the hypothesis of plantations serving as large carbon sinks is not supported by our study.