Cultivation and morphology of jujube (Ziziphus Jujuba Mill.) in the Qi River Basin of Northern China during the Neolithic Period.

This transition from gathering to cultivation is a significant aspect of studying early agricultural practices. Fruit trees are an essential component of food resources and have played a vital role in both ancient and modern agricultural production systems. The jujube (Ziziphus jujuba Mill.), with its long history of cultivation in northern China, holds great importance in uncovering the diet of prehistoric humans and understanding the origins of Chinese agricultural civilization. This paper focuses on the domestication of jujube by analyzing the morphology of jujube stones found in three Neolithic sites in northern China's Qi River basin, Zhujia, Wangzhuang, and Dalaidian. The measurements of these jujube kernels are compared with those found in other areas of northern China, as well as modern jujube kernels that were collected. The measurements revealed that the length-to-diameter (L/D) ratio of sour jujube kernels ranged from 1.36 to 1.78, whereas the L/D ratio of cultivated jujube stones varied between 1.96 and 4.23. Furthermore, jujube stones obtained from Zhujia and Wangzhuang sites exhibit pointed ends and possess an elongated oval or narrow oval shape overall, which is indicative of clearly artificial domestication traits. Therefore, this study suggests that jujube was selected and cultivated as an important food supplement in the Qi River basin no later than around 6200 BP.

Archaeobotanical evidence of the use of medicinal cannabis in a secular context unearthed from south China.

ETHNOPHARMACOLOGICAL RELEVANCE: As one of the first plants used by ancient people, cannabis has been used for medicinal purposes for thousands of years. The long history of medicinal cannabis use contrasts with the paucity of archaeobotanical records. Moreover, physical evidence of medicinal cannabis use in a secular context is much rarer than evidence of medicinal cannabis use in religious or ritual activities, which impedes our understanding of the history of medicinal cannabis use. AIM OF THE STUDY: This study aims to provide archaeobotanical evidence of medicinal cannabis use and analyse the specific medicinal usage of cannabis in a secular context in ancient times. MATERIALS AND METHODS: Plant remains were collected from the Laoguanshan Cemetery of the Han Dynasty in Chengdu, South China, with the archaeological flotation process and were identified based on morphological and anatomical characteristics. The examination of the medicinal significance of the remains relied on the investigation of the documentation on unearthed medical bamboo slips, the diseases of the tomb occupants, the cemetery's cultural background and Chinese historical records. RESULTS: The botanical remains were accurately identified as cannabis. More than 120 thousand fruits were found, which represents the largest amount of cannabis fruit remains that have been statistically analysed from any cemetery in the world thus far. The cannabis fruits are suspected to have been used for medical purposes in a secular context and were most likely used to stop severe bleeding of the uterus and treat lumbago and/or arthralgia. CONCLUSIONS: The cannabis fruit remains reported here likely represent the first physical evidence of medicinal cannabis use for the treatment of metrorrhagia, severe lumbago, and/or arthralgia. This study emphasizes the importance of the evidence of the diseases suffered by the occupants of the tomb in determining the medicinal use of cannabis in a secular context and contributes to a comprehensive understanding of the ancient history of medicinal cannabis.

Vitamin B6 prevents excessive inflammation by reducing accumulation of sphingosine-1-phosphate in a sphingosine-1-phosphate lyase-dependent manner.

Vitamin B6 is necessary to maintain normal metabolism and immune response, especially the anti-inflammatory immune response. However, the exact mechanism by which vitamin B6 plays the anti-inflammatory role is still unclear. Here, we report a novel mechanism of preventing excessive inflammation by vitamin B6 via reduction in the accumulation of sphingosine-1-phosphate (S1P) in a S1P lyase (SPL)-dependent manner in macrophages. Vitamin B6 supplementation decreased the expression of pro-inflammatory cytokines by suppressing nuclear factor-κB and mitogen-activated protein kinases signalling pathways. Furthermore, vitamin B6-reduced accumulation of S1P by promoting SPL activity. The anti-inflammatory effects of vitamin B6 were inhibited by S1P supplementation or SPL deficiency. Importantly, vitamin B6 supplementation protected mice from lethal endotoxic shock and attenuated experimental autoimmune encephalomyelitis progression. Collectively, these findings revealed a novel anti-inflammatory mechanism of vitamin B6 and provided guidance on its clinical use.

Orcinol glucoside facilitates the shift of MSC fate to osteoblast and prevents adipogenesis via Wnt/ß-catenin signaling pathway.

BACKGROUND: During osteoporosis, bone mesenchymal stem cells (BMSCs) lineage commitment shifts to adipocytes, causing fat accumulation and bone loss in the skeleton. Seeking drugs that could reverse the adipocyte fate determination of BMSCs is critical for osteoporosis therapy. As a traditional Chinese medicine, Rhizoma Curculiginis (Xianmao) has been used to treat bone diseases and promote bone healing, while the effective constituent of it and the underlying mechanisms are unknown. OBJECTIVES: The aim of this study is to unveil the role of orcinol glucoside (OG), one constituent of Rhizoma Curculiginis, in osteoporosis and BMSCs lineage commitment and to explore the underlying mechanisms. METHODS: Micro-CT and three-point bending test were performed to determine the effect of OG on bone structure and strength. qT-PCR and Western blot were performed to determine the expression of osteogenic or adipogenic differentiation markers in BMSCs. Mineralization in differentiated BMSCs was assessed by Alizarin Red staining, and lipid accumulation in the cells was evaluated by Oil Red O staining. All measurements were performed at least three times. RESULTS: OG prevented bone loss by stimulating bone formation and attenuating fat formation in bone. In vitro, OG promoted osteoblastic differentiation and inhibited adipogenic differentiation of BMSCs. Inhibition of Wnt/ß-catenin by ICG-001 significantly reversed the effect of OG on osteogenic and adipogenic differentiation of BMSCs. CONCLUSION: Our study demonstrated the role of OG in alleviating bone loss and fat accumulation in osteoporotic bone, therefore bringing a new therapeutic means to the treatment of osteoporosis.

Vitamin B1 Helps to Limit Mycobacterium tuberculosis Growth via Regulating Innate Immunity in a Peroxisome Proliferator-Activated Receptor-γ-Dependent Manner.

It is known that vitamin B1 (VB1) has a protective effect against oxidative retinal damage induced by anti-tuberculosis drugs. However, it remains unclear whether VB1 regulates immune responses during Mycobacterium tuberculosis (MTB) infection. We report here that VB1 promotes the protective immune response to limit the survival of MTB within macrophages and in vivo through regulation of peroxisome proliferator-activated receptor γ (PPAR-γ). VB1 promotes macrophage polarization into classically activated phenotypes with strong microbicidal activity and enhanced tumor necrosis factor-α and interleukin-6 expression at least in part by promoting nuclear factor-κB signaling. In addition, VB1 increases mitochondrial respiration and lipid metabolism and PPAR-γ integrates the metabolic and inflammatory signals regulated by VB1. Using both PPAR-γ agonists and deficient mice, we demonstrate that VB1 enhances anti-MTB activities in macrophages and in vivo by down-regulating PPAR-γ activity. Our data demonstrate important functions of VB1 in regulating innate immune responses against MTB and reveal novel mechanisms by which VB1 exerts its function in macrophages.

Evolution of prehistoric dryland agriculture in the arid and semi-arid transition zone in northern China.

Based on chronological and archaeobotanical studies of 15 Neolithic and Bronze Age sites from the northern Chinese Loess Plateau and southern Inner Mongolia-the agro-pastoral zone of China-we document changes in the agricultural system over time. The results show that wheat and rice were not the major crops of the ancient agricultural systems in these areas, since their remains are rarely recovered, and that millet cultivation was dominant. Millet agriculture increased substantially from 3000 BC-2000 BC, and foxtail millet evidently comprised a high proportion of the cultivated crop plants during this period. In addition, as the human population increased from the Yangshao to the Longshan periods, the length and width of common millet seeds increased by 20-30%. This demonstrates the co-evolution of both plants and the human population in the region. Overall, our results reveal a complex agricultural-gardening system based on the cultivation of common millet, foxtail millet, soybeans and fruit trees, indicating a high food diversity and selectivity of the human population.

A grazing Gomphotherium in Middle Miocene Central Asia, 10 million years prior to the origin of the Elephantidae.

Feeding preference of fossil herbivorous mammals, concerning the coevolution of mammalian and floral ecosystems, has become of key research interest. In this paper, phytoliths in dental calculus from two gomphotheriid proboscideans of the middle Miocene Junggar Basin, Central Asia, have been identified, suggesting that Gomphotherium connexum was a mixed feeder, while the phytoliths from G. steinheimense indicates grazing preference. This is the earliest-known proboscidean with a predominantly grazing habit. These results are further confirmed by microwear and isotope analyses. Pollen record reveals an open steppic environment with few trees, indicating an early aridity phase in the Asian interior during the Mid-Miocene Climate Optimum, which might urge a diet remodeling of G. steinheimense. Morphological and cladistic analyses show that G. steinheimense comprises the sister taxon of tetralophodont gomphotheres, which were believed to be the general ancestral stock of derived "true elephantids"; whereas G. connexum represents a more conservative lineage in both feeding behavior and tooth morphology, which subsequently became completely extinct. Therefore, grazing by G. steinheimense may have acted as a behavior preadaptive for aridity, and allowing its lineage evolving new morphological features for surviving later in time. This study displays an interesting example of behavioral adaptation prior to morphological modification.

Vitamin B5 Reduces Bacterial Growth via Regulating Innate Immunity and Adaptive Immunity in Mice Infected with Mycobacterium tuberculosis.

The mechanisms by which vitamins regulate immunity and their effect as an adjuvant treatment for tuberculosis have gradually become very important research topics. Studies have found that vitamin B5 (VB5) can promote epithelial cells to express inflammatory cytokines. We aimed to examine the proinflammatory and antibacterial effect of VB5 in macrophages infected with Mycobacterium tuberculosis (MTB) strain H37Rv and the therapeutic potential of VB5 in vivo with tuberculosis. We investigated the activation of inflammatory signal molecules (NF-κB, AKT, JNK, ERK, and p38), the expression of two primary inflammatory cytokines (tumor necrosis factor and interleukin-6) and the bacterial burdens in H37Rv-infected macrophages stimulated with VB5 to explore the effect of VB5 on the inflammatory and antibacterial responses of macrophages. We further treated the H37Rv-infected mice with VB5 to explore VB5's promotion of the clearance of H37Rv in the lungs and the effect of VB5 on regulating the percentage of inflammatory cells. Our data showed that VB5 enhanced the phagocytosis and inflammatory response in macrophages infected with H37Rv. Oral administration of VB5 decreased the number of colony-forming units of H37Rv in lungs of mice at 1, 2, and 4 weeks after infection. In addition, VB5 regulated the percentage of macrophages and promoted CD4+ T cells to express interferon-γ and interleukin-17; however, it had no effect on the percentage of polymorphonuclear neutrophils, CD4+ and CD8+ T cells. In conclusion, VB5 significantly inhibits the growth of MTB by regulating innate immunity and adaptive immunity.

The Multiplicity of Infection-Dependent Effects of Recombinant Adenovirus Carrying HGF Gene on the Proliferation and Osteogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells.

Absence of effective therapeutic methods for avascular necrosis of femoral head (ANFH) is still perplexing the world's medical community. Bone marrow mesenchymal stem cells (BMSCs) adoptive cell therapy combined with core decompression is a promising modality, which is highly dependent on the cellular activities of BMSCs. Hepatocyte growth factor (HGF) is a survival factor for BMSCs, yet the underlying mechanism is not fully elucidated. In this study, the effects of multiplicity of infections (MOIs) of recombinant adenovirus carrying HGF gene (rAd-HGF) on human BMSC proliferation and osteogenic differentiation were systemically examined. Infection of rAd-HGF produced secretory HGF and promoted hBMSC proliferation in a MOI-dependent manner, while the osteogenesis was also strengthened as indicated by enhanced calcium nodule formation with the strongest effects achieved at MOI = 250. Blocking the activities of c-MET or its downstream signaling pathways, WNT, ERK1/2, and PI3K/AKT led to differential consequents. Specifically, blockage of the WNT pathway significantly promoted osteogenic differentiation, which also showed additive effects when combined application with rAd-HGF. Our data demonstrated the pro-osteogenic effects of optimized MOIs of rAd-HGF, while inhibition of WNT pathway or activation of PI3K/AKT pathway may act as candidate adjuvant modalities for promoting osteogenic differentiation in rAd-HGF-modified hBMSC treatment on ANFH.