Depression, a severe psychiatric disorder, has been studied for decades, but the underlying mechanisms still remain largely unknown. Depression is closely associated with alterations in dendritic spine morphology and spine density. Therefore, understanding dendritic spines is vital for uncovering the mechanisms underlying depression. Several chronic stress models, including chronic restraint stress (CRS), chronic unpredictable mild stress (CUMS), and chronic social defeat stress (CSDS), have been used to recapitulate depression-like behaviors in rodents and study the underlying mechanisms. In comparison with CRS, CUMS overcomes the stress habituation and has been widely used to model depression-like behaviors. CSDS is one of the most frequently used models for depression, but it is limited to the study of male mice. Generally, chronic stress causes dendritic atrophy and spine loss in the neurons of the hippocampus and prefrontal cortex. Meanwhile, neurons of the amygdala and nucleus accumbens exhibit an increase in spine density. These alterations induced by chronic stress are often accompanied by depression-like behaviors. However, the underlying mechanisms are poorly understood. This review summarizes our current understanding of the chronic stress-induced remodeling of dendritic spines in the hippocampus, prefrontal cortex, orbitofrontal cortex, amygdala, and nucleus accumbens and also discusses the putative underlying mechanisms.

Helicobacter pylori (H. pylori) is a common human pathogenic bacterium. Once infected, it is difficult for the host to clear this organism using the innate immune system. Increased antibiotic resistance further makes it challenging for effective eradication. However, the mechanisms of immune evasion still remain obscure, and novel strategies should be developed to efficiently eliminate H. pylori infection in stomachs. Here we uncovered desirable anti-H. pylori effect of vitamin D3 both in vitro and in vivo, even against antibiotic-resistant strains. We showed that H. pylori can invade into the gastric epithelium where they became sequestered and survived in autophagosomes with impaired lysosomal acidification. Vitamin D3 treatment caused a restored lysosomal degradation function by activating the PDIA3 receptor, thereby promoting the nuclear translocation of PDIA3-STAT3 protein complex and the subsequent upregulation of MCOLN3 channels, resulting in an enhanced Ca 2+ release from lysosomes and normalized lysosomal acidification. The recovered lysosomal degradation function drives H. pylori to be eliminated through the autolysosomal pathway. These findings provide a novel pathogenic mechanism on how H. pylori can survive in the gastric epithelium, and a unique pathway for vitamin D3 to reactivate the autolysosomal degradation function, which is critical for the antibacterial action of vitamin D3 both in cells and in animals, and perhaps further in humans.

On the basis of station observations, an atmospheric field (ObsFC) was constructed for the Community Land Model version 3.5 (CLM3.5). The model (CLM3.5 driven with ObsFC, hereafter referred as to CLM3.5/ObsFC) was used to simulate soil moisture (SM) from 1951 to 2008 in China. The resulting SM was compared with in situ observations, remote-sensing data and estimations made by various land models, indicating that CLM3.5/ObsFC is capable of reproducing the temporospatial characteristics and long-term variation trends of SM over China. Using an in situ observation-based forcing field improves the simulation of SM. Analysis of SM simulated using CLM3.5/ObsFC shows that the overall spatial pattern of SM was characterized by a gradually decreasing and alternating distribution of arid-humid zones from the southeast to northwest. Regionally averaged SM was the driest over southern Xinjiang Province and western Inner Mongolia, while the most humid regions were located over the Northeast Plain, Jianghuai region and the Yangtze River basin. The long-term variation trends of SM were generally characterized by increases in arid and humid regions and decreases in semiarid regions. Moreover, the variation was relatively intense from the mid-1970s to the mid-1990s in the arid region. The time series was more stable in the humid region except for a period near 1970 and after the year 2003. A downward trend was most prominent in the semiarid region from the 1990s to the end of the time series. Koster et al. [3] supported the mechanism of feedback between SM and precipitation on regional and continental scales. SM alters the processes of the water cycle between the land surface and the atmosphere, influencing precipitation, energy-cycle processes, and temperature [4]. Dai et al. in 1999 [5], demonstrated that SM reduces the diurnal temperature range in the lower atmosphere via evaporative cooling. In addition, SM is a relatively slowly varying component, having several months of "memory" of climatic information [6]. The Global Land-

BackgroundTumor necrosis factor alpha (TNFα) and interferon gamma (IFNγ) were originally identified to show potent anti-tumor activity and immunomodulatory capability. Unfortunately, several clinical studies of relevant cancer therapy did not observe significant response in maximum tolerated dose whether given alone or in combination. We have identified a tumor vasculature homing peptide (TCP-1 peptide) which targets only the vasculature of colorectal tumors but not normal blood vessels in animals and humans. In the current study, the antitumor effect of TCP-1/TNFα and TCP-1/IFNγ alone or in combination was studied in orthotopic colorectal tumor model.MethodsTCP-1/TNFα and TCP-1/IFNγ recombinant proteins were prepared and i.v. injected to study the in vivo anticancer effect in orthotopic colorectal tumor model. Tumor apoptosis was determined by TUNEL staining and cleaved caspase-3 immunofluorescent staining. Tumor infiltrating lymphocytes were analyzed by immunofluorescent staining and flow cytometry. Western-blot was performed to examine the expression of proteins. Cell apoptosis was measured by Annexin V/PI flow cytometry.ResultsTargeted delivery of TNFα or IFNγ by TCP-1 peptide exhibited better antitumor activity than unconjugated format by inducing more tumor apoptosis and also enhancing antitumor immunity shown by increased infiltration of T lymphocytes inside the tumor. More importantly, combination therapy of TCP-1/TNFα and TCP-1/IFNγ synergistically suppressed tumor growth and alleviated systematic toxicity associated with untargeted therapy. This combination therapy induced massive apoptosis/secondary necrosis in the tumor.ConclusionsTaken together, our data demonstrate TCP-1 is an efficient drug carrier for targeted therapy of colorectal cancer (CRC). TCP-1/TNFα combined with TCP-1/IFNγ is a promising combination therapy for CRC.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-016-0944-3) contains supplementary material, which is available to authorized users.