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Diffuse large B-cell lymphoma (DLBCL) may present initially in bone marrow, liver and spleen without any lymphadenopathy (referred to as BLS-type DLBCL), which is aggressive and frequently associated with hemophagocytic syndrome. Its tumorigenesis and molecular mechanisms warrant clarification. By gene microarray profiling with bioinformatics analysis, we found higher expression of the stem cell markers HOXA9 and NANOG, as well as BMP8B, CCR6 and S100A8 in BLS-type than conventional DLBCL. We further validated expression of these markers in a large cohort of DLBCL including BLS-type cases and found that expression of HOXA9 and NANOG correlated with inferior outcome and poor prognostic parameters. Functional studies with gene-overexpressed and gene-silenced DLBCL cell lines showed that expression of NANOG and HOXA9 promoted cell viability and inhibited apoptosis through suppression of G2 arrest in vitro and enhanced tumor formation and hepatosplenic infiltration in a tail-vein-injected mouse model. Additionally, HOXA9-transfected tumor cells showed significantly increased soft-agar clonogenic ability and tumor sphere formation. Interestingly, B cells with higher CCR6 expression revealed a higher chemotactic migration for CCL20. Taken together, our findings support the concept that tumor or precursor cells of BLS-type DLBCL are attracted by chemotaxis and home to the bone marrow, where the microenvironment promotes the expression of stem cell characteristics and aggressiveness of tumor cells.

The invasion ability of glioblastoma (GBM) causes tumor cells to infiltrate the surrounding brain parenchyma and leads to poor outcomes. Transient receptor potential vanilloid 4 (TRPV4) exhibits a remarkable role in cancer cell motility, but the contribution of TRPV4 to glioblastoma metastasis is not fully understood. Here, we reported that TRPV4 expression was significantly elevated in malignant glioma compared to normal brain and low-grade glioma, and TRPV4 expression was negatively correlated with the prognosis of glioma patients. Functionally, stimulation of TRPV4 promoted glioblastoma cell migration and invasion, and repression of TRPV4 hindered the migration and invasion of glioblastoma cells in vitro. Molecularly, TRPV4 strongly colocalized and interacted with skeletal protein-F-actin at cellular protrusions, and TRPV4 regulated the formation of invadopodia and filopodia in glioblastoma cells. Furthermore, the Cdc42/N-wasp axis mediated the effect of TRPV4-regulated cellular protrusions and invasion. Foremost, TRPV4 inhibitor treatment or downregulation of TRPV4 significantly reduced the invasion-growth of subcutaneously and intracranially transplanted glioblastoma in mice. In conclusion, the TRPV4/Cdc42/wasp signaling axis regulates cellular protrusion formation in glioblastoma cells and influences the invasion-growth phenotype of glioblastoma in vivo. TRPV4 may serve as a prognostic factor and specific therapeutic target for GBM patients.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

In southeastern China (SEC), the precipitation amount produced by the East Asian summer monsoon (EASM) is almost equivalent to that during the non-summer monsoon (NSM) period, both of them significantly affecting agriculture and socioeconomy. Here, we present a seasonally-resolved stalagmite δ18O record (δ18Os) for the interval 1810–2009 AD from E’mei cave, Jiangxi Province, SEC. The comparison between δ18Os and instrumental data indicates that the δ18Os variability is primarily controlled by the precipitation seasonality (i.e., the ratio of EASM/NSM precipitation) modulated by the El Niño/Southern Oscillation (ENSO) on interannual to interdecadal timescales. Higher (lower) δ18Os values thereby correspond to lower (higher) EASM/NSM ratios associated with El Niño (La Niña) events. Significant correlations with ENSO and the Pacific Decadal Oscillation (PDO) indicate that the precipitation seasonality in SEC is remarkably influenced by ocean-atmosphere interactions, with lower (higher) EASM/NSM ratios during warm (cold) phases of ENSO/PDO. The progressive increase in δ18Os since 2005 AD may reflect a strengthening of the central Pacific El Niño under continued anthropogenic global warming. The relationship between seasonal precipitation and δ18Os with ENSO/PDO requires further studies.

Intermontane basins in the southern piedmont of the Qinling Mountains are important sources of information on hominin occupation and settlement, and provide an excellent opportunity to study early human evolution and behavioral adaptation. Here, we present the results of a detailed magnetostratigraphic investigation of the sedimentary sequence of hominin-bearing Bailong Cave in Yunxi Basin, central China. Correlation to the geomagnetic polarity time scale was achieved using previously published biostratigraphy, 26Al/10Be burial dating, and coupled electron spin resonance (ESR) and U-series dating. The Bailong Cave hominin-bearing layer is dated to the early Brunhes Chron, close to the Matuyama-Brunhes geomagnetic reversal at 0.78 Ma. Our findings, coupled with other records, indicate the flourishing of early humans in mainland East Asia during the Mid-Pleistocene climate transition (MPT). This suggests that early humans were adapted to diverse and variable environments over a broad latitudinal range during the MPT, from temperate northern China to subtropical southern China.

The extent to which climate variability in Central Asia is causally linked to large-scale changes in the Asian monsoon on varying timescales remains a longstanding question. Here we present precisely dated high-resolution speleothem oxygen-carbon isotope and trace element records of Central Asia’s hydroclimate variability from Tonnel’naya cave, Uzbekistan and Kesang cave, western China. On orbital timescales, the supra-regional climate variance, inferred from our oxygen isotope records, exhibits a precessional rhythm, punctuated by millennial-scale abrupt climate events, suggesting a close coupling with the Asian monsoon. However, the local hydroclimatic variability at both cave sites, inferred from carbon isotope and trace element records, shows climate variations that are distinctly different from their supra-regional modes. Particularly, hydroclimatic changes in both Tonnel’naya and Kesang areas during the Holocene lag behind the supra-regional climate variability by several thousand years. These observations may reconcile the apparent out-of-phase hydroclimatic variability, inferred from the Holocene lake proxy records, between Westerly Central Asia and Monsoon Asia.

The Bohai Basin was transformed to an inner shelf sea hundreds of thousands years ago. This youngest land-sea transition participated in the significant modification of the distribution of fresh water, sediment fluxes and climate in East Asia and played an important role in the origin of the Asian marginal seas. Here we present the results of a magnetostratigraphic investigation and propose a conceptual model for the land-sea transition. Our findings indicate that the transition probably started several million years ago, from a fluvial system during the late Miocene and early Pliocene, to a lacustrine environment between the late Pliocene and Middle Pleistocene and finally to a marine system in the late Pleistocene. Comparison of our results with previous research suggests that the Bohai Paleolake was initiated from the late Pliocene, was fully developed prior to ~1.0 Ma and terminated around the late Middle Pleistocene. The Miaodao Islands formed the eastern “barrier” of the basin and since the Pliocene or earlier they played a significant role in blocking the lake water and sediments. They deformed from ~1.0 Ma, subsided significantly at ~0.3 Ma and completely by ~0.1 Ma, resulting in the maturation of the basin as an inner shelf sea.

The Indian summer monsoon (ISM) monsoon is critical to billions of people living in the region. Yet, significant debates remain on primary ISM drivers on millennial-orbital timescales. Here, we use speleothem oxygen isotope (δ18O) data from Bittoo cave, Northern India to reconstruct ISM variability over the past 280,000 years. We find strong coherence between North Indian and Chinese speleothem δ18O records from the East Asian monsoon domain, suggesting that both Asian monsoon subsystems exhibit a coupled response to changes in Northern Hemisphere summer insolation (NHSI) without significant temporal lags, supporting the view that the tropical-subtropical monsoon variability is driven directly by precession-induced changes in NHSI. Comparisons of the North Indian record with both Antarctic ice core and sea-surface temperature records from the southern Indian Ocean over the last glacial period do not suggest a dominant role of Southern Hemisphere climate processes in regulating the ISM variability on millennial-orbital timescales.