Climate effects and human impacts, that is, nutrient enrichment, simultaneously drive spatial biodiversity patterns. However, there is little consensus about their independent effects on biodiversity. Here we manipulate nutrient enrichment in aquatic microcosms in subtropical and subarctic regions (China and Norway, respectively) to show clear segregation of bacterial species along temperature gradients, and decreasing alpha and gamma diversity toward higher nutrients. The temperature dependence of species richness is greatest at extreme nutrient levels, whereas the nutrient dependence of species richness is strongest at intermediate temperatures. For species turnover rates, temperature effects are strongest at intermediate and two extreme ends of nutrient gradients in subtropical and subarctic regions, respectively. Species turnover rates caused by nutrients do not increase toward higher temperatures. These findings illustrate direct effects of temperature and nutrients on biodiversity, and indirect effects via primary productivity, thus providing insights into how nutrient enrichment could alter biodiversity under future climate scenarios.

Although elevational gradients in microbial biodiversity have attracted increasing attention recently, the generality in the patterns and underlying mechanisms are still poorly resolved. Further, previous studies focused mostly on species richness, while left understudied evenness, another important aspect of biodiversity. Here, we studied the elevational patterns in species richness and evenness of stream biofilm bacteria and diatoms in six mountains in Asia and Europe. We also reviewed published results for elevational richness patterns for soil and stream microbes in a literature analysis. Our results revealed that even within the same ecosystem type (that is, stream) or geographical region, bacteria and diatoms showed contrasting patterns in diversity. Stream microbes, including present stream data, tend to show significantly increasing or decreasing elevational patterns in richness, contrasting the findings for soil microbes that typically showed nonsignificant or significantly decreasing patterns. In all six mountains for bacteria and in four mountains for diatoms, species richness and evenness were positively correlated. The variation in bacteria and diatom richness and evenness were substantially explained by anthropogenic driven factors, such as total phosphorus (TP). However, diatom richness and evenness were also related to different main drivers as richness was mostly related to pH, while evenness was most explained by TP. Our results highlight the lack of consistent elevational biodiversity patterns of microbes and further indicate that the two facets of biodiversity may respond differently to environmental gradients.

It is well known that insulin can activate both PI3K/Akt pathway, which is responsible for glucose uptake, and MAPK pathway, which is crucial for insulin resistance formation. But, it is unclear exactly how the two pathways coordinate to regulate insulin sensitivity upon hyperinsulinism stress of type 2 diabetes mellitus (T2DM). Here, we show that an early response transcription factor Egr-1 could tilt the signalling balance by blocking PI3K/Akt signalling through PTEN and augmenting Erk/MAPK signalling through GGPPS, resulting in insulin resistance in adipocytes. Egr-1, PTEN and GGPPS are upregulated in the fat tissue of T2DM patients and db/db mice. Egr-1 overexpression in epididymal fat induced systematic insulin resistance in wild-type mice, and loss of Egr-1 function improved whole-body insulin sensitivity in diabetic mice, which is mediated by Egr-1 controlled PI3K/Akt and Erk/MAPK signalling balance. Therefore, we have revealed, for the first time, the mechanism by which Egr-1 induces insulin resistance under hyperinsulinism stress, which provides an ideal pharmacological target since inhibiting Egr-1 can simultaneously block MAPK and augment PI3K/Akt activation during insulin stimulation.

Lung cancer is one of the leading causes of cancer mortality worldwide. The therapeutic effect of chemotherapy is limited due to the resistance of cancer cells, which remains a challenge in cancer therapeutics. In this work, we found that flap endonuclease 1 (FEN1) is overexpressed in lung cancer cells. FEN1 is a major component of the base excision repair pathway for DNA repair systems and plays important roles in maintaining genomic stability through DNA replication and repair. We showed that FEN1 is critical for the rapid proliferation of lung cancer cells. Suppression of FEN1 resulted in decreased DNA replication and accumulation of DNA damage, which subsequently induced apoptosis. Manipulating the amount of FEN1 altered the response of lung cancer cells to chemotherapeutic drugs. A small‐molecule inhibitor (C20) was used to target FEN1 and this enhanced the therapeutic effect of cisplatin. The FEN1 inhibitor significantly suppressed cell proliferation and induced DNA damage in lung cancer cells. In mouse models, the FEN1 inhibitor sensitized lung cancer cells to a DNA damage‐inducing agent and efficiently suppressed cancer progression in combination with cisplatin treatment. Our study suggests that targeting FEN1 may be a novel and efficient strategy for a tumor‐targeting therapy for lung cancer.