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Summary: Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis (Mtb) infection, with the highest single-cause mortality. Monocarboxylate transporter 4 (Mct4) transports intracellular lactate outside, but its role in regulating host immune response against Mtb infection remains unknown. Mct4 expression was upregulated in Mtb-infected macrophages and in patients with TB. Mct4 silencing/deficiency significantly decreased Mtb survival in macrophages and in lungs and spleens of mice, while Mct4 overexpression facilitated Mtb survival in macrophages. Furthermore, Mct4 promoted intracellular lactate transport, nuclear factor κB (NF-κB) p65 activation, and interleukin-10 (IL-10) production upon Mtb infection. Mechanistically, IL-10 silencing and IL-10-neutralizing antibody blocked Mct4 overexpressing increased Mtb survival. Replenishing lactate and NF-κB p65 inhibitor JSH23 treatment could inhibit Mct4 overexpressing increased NF-κB p65 activation, IL-10 production, and Mtb survival in macrophages. This study demonstrates that Mct4 promotes Mtb survival through restricting intracellular lactate accumulation to promote NF-κB p65-mediated IL-10 production and suggests Mct4-NF-κB p65-IL-10 axis a potential target for TB treatment.

Abstract 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.

With the gradual depletion of fossil energy sources and the diversification of users’ energy demand, combined cooling, heating and power (CCHP) microgrids have become a hot technology to improve energy efficiency and promote efficient and synergistic energy operation. However, the uncertainty and correlation of wind power and photovoltaic (PV) outputs have posed a great challenge to the reliability of CCHP system operation, so CCHP systems are often equipped with energy storage devices to improve system flexibility to ensure the reliability of energy supply. However, system-owned reserves still have shortcomings such as high investment O&M costs and large space requirements. As an emerging model, “shared energy storage” can reduce the investment pressure of users and open up new ways for the economic and stable operation of CCHP systems. Therefore, based on the scenario of wind and solar power correlation and considering different types of load flexibility, this paper proposes to construct a shared energy storage station (SESS)-CCHP double-layer synergistic optimal allocation model. The model incorporates the consideration of the actual operation strategy of the CCHP system in the planning stage of energy storage. An example analysis shows that SESS reduces the total operating cost of the CCHP system by 25.96% and improves the new energy consumption rate by 10.46% compared with no energy storage. Compared with the system independently configured with energy storage, the cost saving is 2.14%, thus validating the effectiveness of the proposed model.

Summary: The typical genomic feature of acute myeloid leukemia (AML) M3 subtype is the fusion event of PML/RARα, and ATRA/ATO-based combination therapy is current standard treatment regimen for M3 subtype. Here, a machine-learning model based on expressions of PML/RARα targets was developed to identify M3 patients by analyzing 1228 AML patients. Our model exhibited high accuracy. To enable more non-M3 AML patients to potentially benefit from ATRA/ATO therapy, M3-like patients were further identified. We found that M3-like patients had strong GMP features, including the expression patterns of M3 subtype marker genes, the proportion of myeloid progenitor cells, and deconvolution of AML constituent cell populations. M3-like patients exhibited distinct genomic features, low immune activity and better clinical survival. The initiative identification of patients similar to M3 subtype may help to identify more patients that would benefit from ATO/ATRA treatment and deepen our understanding of the molecular mechanism of AML pathogenesis.

Abstract Key message Here, we present a workflow for determining the optimal tree height model and calibration design for forests affected to varying degrees by anthropogenic disturbance. For mixed Araucaria-Nothofagus forests, tree height predictions in newly surveyed stands are most accurate and effective when the height of up to five random trees is measured to recalibrate predefined nonlinear mixed-effects models. Context Araucaria-Nothofagus forests in Chile are affected by anthropogenic disturbances such as intentional forest fires, grazing, and seed harvesting, causing forest structure to become more heterogeneous. This also challenges tree height predictions, which are required for yield estimations, carbon accounting, and forest management, since height measurements of standing trees are often considered too costly, difficult, and imprecise. Aims How does the structure of these forests vary by different levels of anthropogenic disturbance? Which models for estimating tree height of Araucaria araucana and Nothofagus pumilio are most reliable and generally usable? And considering their application in stands they have not been fitted to, which calibration design is optimal for these models? Methods Twelve stands were surveyed and classified into four different intensities of anthropogenic disturbance. In 25 to 36 plots per stand, horizontal point sampling measurements of stem diameter as well as of height of selected trees were carried out. Different quantitative stand-level properties were calculated to determine forest structure, which was compared among stands by cluster analysis. To identify the optimal height-diameter (H–D) model, simple models including diameter only as well as generalized models including stand variables were tested, each additionally extended by a nonlinear mixed-effects (NLME) modeling framework accounting for nested and random effects. To further determine tree height in new stands, the optimal model calibration design was identified involving the empirical best unbiased predictor technique. Results Forest structure greatly varied among stands affected by different levels of anthropogenic disturbance, which challenged the development of tree height prediction models. Of all the simple H–D models considered, the Gompertz model was the best for A. araucana and the Näslund model for N. pumilio. The models progressively improved by adding stand variables and using NLME techniques. However, our final model comparisons indicate that a calibrated simple NLME model without stand variables should be preferred. It was further found that the optimal calibration design is to use five randomly selected trees. Conclusion Although anthropogenic disturbances can have a complex effect on height-diameter relationships, the same H–D model can be used for stands representing different anthropogenic disturbance levels and recalibrated by cost-effective measurements.

Background: Ovarian cancer is a highly lethal gynecologic malignancy. ARHGAP10, a member of Rho GTPase-activating proteins, is a potential tumor suppressor in ovarian cancer. However, its role and the involved mechanism need further examination. Here, we investigated whether ARHGAP10 is also associated with ferroptosis. Methods: Lentivirus infection was used for gene overexpression or silencing. Real-time polymerase chain reaction (RT-PCR) and Western blot were used to assess mRNA and protein levels, respectively. Cell viability was assessed by Cell Counting Kit-8 (CCK-8) assay. Lipid reactive oxygen species level was measured by flow cytometry. A tumorigenicity assay was performed to evaluate tumor growth in vivo, and sections of mouse tumor tissues were examined by immunofluorescence microscopy. Chromatin Immunoprecipitation (ChIP) assay was used to assess the binding of H3K9ac to the promoter region of ARHGAP10. Results: ARHGAP10 overexpression promoted ferroptosis in ovarian cancer cells, resulting in decreased cell viability, and increased lipid reactive oxygen species (ROS) level. Further, it decreased and increased GPX4 and PTGS2 expression, respectively, and also induced suppression of tumor growth in mice. Fer-1, a potent inhibitor of ferroptosis, suppressed the above effects of ARHGAP10. Contrarily, ARHGAP10 silencing alleviated ferroptosis in ovarian cancer cells, which was reversed by RSL3, a ferroptosis-inducing agent. Lastly, sodium butyrate (SB) was found to transcriptionally regulate ARHGAP10, thereby also contributing to the ferroptosis of ovarian cancer cells. Conclusions: Our results suggest that SB/ARHGAP10/GPX4 is a new signaling axis involved in inducing ferroptosis in ovarian cancer cells and suppressing tumor growth, which has potential clinical significance.

Abstract The region of Transoxiana underwent an early agricultural-demographic transition leading to the earliest proto-urban centers in Central Asia. The agronomic details of this cultural shift are still poorly studied, especially regarding the role that long-generation perennials, such as grapes, played in the cultivation system. In this paper, we present directly dated remains of grape pips from the early urban centers of Sapalli and Djarkutan, in south Uzbekistan. We also present linear morphometric data, which illustrate a considerable range of variation under cultivation that we divide into four distinct morphotypes according to pip shape. While some of the pips in these two assemblages morphologically fall within the range of wild forms, others more closely resemble modern domesticated populations. Most of the specimens measure along a gradient between the two poles, showing a mixed combination of domesticated and wild features. We also point out that the seeds recovered from the Djarkutan temple were, on average, larger and contained more affinity towards domesticated forms than those from domestic contexts. The potential preference of morphotypes seems to suggest that there were recognized different varieties that local cultivators might aware and possibly propagating asexually.

Changes in fire ecology during warm and cold periods in the geological past are important because of their effects on terrestrial ecosystems and the global carbon cycle. We examined the charcoal concentrations of the Erden Obo section in Inner Mongolia to reconstruct the evolution of wildfire and their relationship to the regional vegetation from the Late Paleocene through Early Oligocene. Our data show that fire frequency were relatively high from the end of the Paleocene to the beginning of the Eocene, in accord with other paleofire records worldwide. However, low fire frequency occurred during the Early Eocene Climate Optimum (EECO), coincident with the change in the regional vegetation from shrubland to forest due to the strengthening of the regional rainfall, and we suggest that the humid climate may have been responsible for this decrease. High frequency fire occurred after the Middle Eocene, near-synchronously with the transition of the regional vegetation from forest to steppe. The high-frequency fire was most likely triggered by regional drought during the aridification process after the Middle Eocene. We propose that these temporal changes in the fire ecology were consistent within the northern temperate zone from the Late Paleocene through Early Oligocene, and we suggest that studies of global wildfires need to be evaluated within the context of paleovegetation zones and ecosystem evolution.

BackgroundYupingfeng granules (YPFG) contribute to various chronic respiratory infections. Several clinical studies have evaluated its efficacy and safety in treating recurrent respiratory tract infections (RRTIs) in children. However, the evidence for its use has not been conclusively proven.ObjectiveThe aim of this study was to demonstrate the efficacy and safety of YPFG in the adjuvant treatment of RRTIs in children.MethodsWe searched PubMed, Embase, Web of Science, Cochrane Library, Clinical Trials, Chinese Clinical Trial Registry, Sinomad, China National Knowledge Infrastructure (CNKI), Wanfang Database, and Chinese Scientific Journals Database (VIP) for randomized controlled trials (RCTs) of YPFG adjuvant therapy for children with RRTIs as of September 1, 2022. We screened the literature for inclusion and exclusion criteria, assessed the quality of each included literature, and then extracted data from each study for this systematic review and meta-analysis.ResultsA total of 17 RCTs were included. Data analysis showed that the total clinical response rate in the YPFG group was significantly higher than that in the control group [risk ratio (RR) = 1.18, 95%CI (1.12, 1.24), I2 = 39%, P

Abstract Rice is one of the most culturally valued and widely grown crops in the world today, and extensive research over the past decade has clarified much of the narrative of its domestication and early spread across East and South Asia. However, the timing and routes of its dispersal into West Asia and Europe, through which rice eventually became an important ingredient in global cuisines, has remained less clear. In this article, we discuss the piecemeal, but growing, archaeobotanical data for rice in West Asia. We also integrate written sources, linguistic data, and ethnohistoric analogies, in order to better understand the adoption of rice outside its regions of origin. The human-mediated westward spread of rice proceeded gradually, while its social standing and culinary uses repeatedly changing over time and place. Rice was present in West Asia and Europe by the tail end of the first millennium BC, but did not become a significant crop in West Asia until the past few centuries. Complementary historical, linguistic, and archaeobotanical data illustrate two separate and roughly contemporaneous routes of westward dispersal, one along the South Asian coast and the other through Silk Road trade. By better understanding the adoption of this water-demanding crop in the arid regions of West Asia, we explore an important chapter in human adaptation and agricultural decision making.

Abstract Ancient DNA research has developed rapidly over the past few decades due to improvements in PCR and next‐generation sequencing (NGS) technologies, but challenges still exist. One major challenge in relation to ancient DNA research is to recover genuine endogenous ancient DNA sequences from raw sequencing data. This is often difficult due to degradation of ancient DNA and high levels of contamination, especially homologous contamination that has extremely similar genetic background with that of the real ancient DNA. In this study, we collected whole‐genome sequencing (WGS) data from 6 ancient samples to compare different mapping algorithms. To further explore more effective methods to separate endogenous DNA from homologous contaminations, we attempted to recover reads based on ancient DNA specific characteristics of deamination, depurination, and DNA fragmentation with different parameters. We propose a quick and improved pipeline for separating endogenous ancient DNA while simultaneously decreasing homologous contaminations to very low proportions. Our goal in this research was to develop useful recommendations for ancient DNA mapping and for separation of endogenous DNA to facilitate future studies of ancient DNA.

Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) infection is the deadliest infectious disease and a global health problem. Macrophages (Mφs) and neutrophils that can phagocytose Mtb represent the first line of immune response to infection. Glycogen synthase kinase-3α/β (GSK-3α/β) represents a regulatory switch in host immune responses. However, the efficacy and molecular mechanisms of how GSK-3α/β interacts with Mtb infection in Mφs remain undefined. Here, we demonstrated that Mtb infection downregulated GSK-3α/β activity and promoted matrix metalloproteinase-1 (MMP-1) and MMP-9 expressions in Mφs derived from acute monocytic human leukemia THP-1 cells (THP-1-Mφs). We confirmed the upregulation of MMP-9 expression in tissues of TB patients compared with patients of chronic inflammation (CI). In THP-1-Mφs and C57BL/6 mice, GSK-3α/β inhibitor SB216763 significantly increased MMP-1/9 production and facilitated Mtb load, while MMP inhibitors blocked MMP-1/9 expression and Mtb infection. Consistently, GSK-3α/β silencing significantly increased MMP-1/9 expression and Mtb infection, while overexpression of GSK-3α/β and constitutive activated GSK-3α/β mutants significantly reduced MMP-1/9 expression and Mtb infection in THP-1-Mφs. MMP-1/9 silencing reduced Mtb infection, while overexpression of MMP-1/9 promoted Mtb infection in THP-1-Mφs. We further found that GSK-3α/β inhibition increased Mtb infection and MMP-1/9 expression was blocked by ERK1/2 inhibitor. Additionally, we showed that protein kinase C-δ (PKC-δ) and mammalian target of rapamycin (mTOR) reduced GSK-3α/β activity and promoted MMP-1/9 production in Mtb-infected THP-1-Mφs. In conclusion, this study suggests that PKC-δ-mTOR axis suppresses GSK-3α/β activation with acceleration of MMP-1/9 expression through phospho-ERK1/2. These results reveal a novel immune escape mechanism of Mtb and a novel crosstalk between these critical signaling pathways in anti-TB immunity.

Background: Osteosarcoma (OS) is the most prevalent bone cancer among children and adolescents, with relatively high mortality rates. RNA N6-methyladenosine (m6A) is the most common human mRNA modification with diverse functions in a variety of biological processes. Previous studies indicated that methyltransferase-like 3 (METTL3), the first methyltransferase to be identified, acted as an oncogene or tumor suppressor in multiple human cancers. However, its functions and underlying mechanisms in OS progression remain unclear; therefore, we explored these processes.Methods: We used real-time quantitative PCR (RT-qPCR) and Western blot assays to explore METTL3 expression in OS tumor tissues and five OS cell lines to assess its clinical significance. To further examine the functional role of METTL3 during OS progression, CCK-8 analyses, transwell assays, and xenograft model studies were conducted after silencing METTL3. Additionally, underlying mechanisms were also explored using RIP-seq and RIP-qPCR approaches.Results: METTL3 was upregulated in OS tumor tissues and cell lines and was associated with a worse prognosis. Moreover, METTL3 silencing suppressed OS cell proliferation, migration, and invasion. Also, in vivo METTL3 oncogenic functions were confirmed in the xenograft model. Comprehensive mechanistic analyses identified long non-coding RNA (lncRNA) DANCR as a potential target of METTL3, as indicated by reduced DANCR levels after METTL3 silencing. Also, lncRNA DANCR knockdown repressed OS cell proliferation, migration, and invasion. Furthermore, both METTL3 and lncRNA DANCR silencing significantly suppressed OS growth and metastasis. Finally, we hypothesized that METTL3 regulated DANCR expression via m6A modification-mediated DANCR mRNA stability.Conclusion: METTL3 contributes to OS progression by increasing DANCR mRNA stability via m6A modification, meaning that METTL3 may be a promising therapeutic target for OS treatment.

Background The purpose of our research was to explore potential value of lncRNA-BC050642 in osteosarcoma origination and prognosis.Methods In this study, the tissue specimens were collected from 97 osteosarcoma patients and 97 age-matched healthy controls. Besides, human osteosarcoma cell lines U2OS and normal osteoblastic cell line hFOB1.19 were selected for experiments in vitro. lncRNA-BC050642 levels were measured through quantitative real-time polymerase chain reaction (qRT-PCR). Relative expression of the gene c-myc was determined via ELISA analysis. x2 test was implemented to appraise possible relationship between BC050642 level and clinicopathological features. Cell proliferation assay, plate colony formation assay, and cell apoptosis assay were adopted to analyze the influence of BC050642 on tumor development. Besides, prognostic value of BC050642 was estimated using Kaplan–Meier and cox regression analysis.Results BC050642 levels showed distinctive increases in osteosarcoma tissues and cell lines compared with controls. And c-myc expression was down-regulated in osteosarcoma. There was a negative correlation between the expressions of BC050642 and c-myc. BC050642 expression was proved to be significantly correlated with Ennking and histological type. Up-regulated BC050642 could promote cell proliferation, induce colony formation and meanwhile inhibit cell apoptosis.Conclusions BC050642 is up-regulated in osteosarcma and its over-expression promotes tumor development via down-regulating the expression of c-myc. It also may be an independent prognostic biomarker for osteosarcoma.

Eastern and Western Asia were important centers for the domestication of plants and animals and they developed different agricultural practices and systems. The timing, routeway and mechanisms of the exchanges between the two centers have long been important scientific issues. The development of a mixed pastoral system (e.g., with the rearing of sheep, goats and cattle) and millet cultivation in the steppe region of northern China was the result of the link between the two cultures. However, little detailed information is available about the precise timing and mechanisms involved in this mixture of pastoralism and millet cultivation. To try to address the issue, we analyzed the pollen, fungal spores and phytolith contents of soil samples from the Bronze Age Zhukaigou site in the steppe area of North China, which was combined with AMS 14C dating of charcoal, millet and animal bones. A mixed pastoralism and millet agricultural system appeared at the site between 4,000 and 3,700 cal yr BP, and the intensity of animal husbandry increased in the later stage of occupation. Published data indicate that domestic sheep/goats appeared across a wide area of the steppe region of northern China after ∼4,000 cal yr BP. A comparison of records of sheep/goat rearing and paleoclimatic records from monsoon area in China leads us to conclude that the mixture of pastoralism and millet cultivation was promoted by the occurrence of drought events during 4,200–4,000 cal yr BP. Moreover, we suggest that mixed rainfed agriculture and animal husbandry increased the adaptability and resilience of the inhabitants of the region which enabled them to occupy the relatively arid environment of the monsoon marginal area of northern China.

Rotavirus infection is a major cause of severe dehydrating diarrhea in infants younger than 5 y old and in particular cases of immunocompromised patients irrespective to the age of the patients. Although vaccines have been developed, antiviral therapy is an important complement that cannot be substituted. Because of the lack of specific approved treatment, it is urgent to facilitate the cascade of further understanding of the infection biology, identification of druggable targets and the final development of effective antiviral therapies. PI3K-Akt-mTOR signaling pathway plays a vital role in regulating the infection course of many viruses. In this study, we have dissected the effects of PI3K-Akt-mTOR signaling pathway on rotavirus infection using both conventional cell culture models and a 3D model of human primary intestinal organoids. We found that PI3K-Akt-mTOR signaling is essential in sustaining rotavirus infection. Thus, blocking the key elements of this pathway, including PI3K, mTOR and 4E-BP1, has resulted in potent anti-rotavirus activity. Importantly, a clinically used mTOR inhibitor, rapamycin, potently inhibited both experimental and patient-derived rotavirus strains. This effect involves 4E-BP1 mediated induction of autophagy, which in turn exerts anti-rotavirus effects. These results revealed new insights on rotavirus-host interactions and provided new avenues for antiviral drug development.

Abstract An air-insulated microfluidic chip was designed for the automatic centrifugal distribution of samples to 24-test cells, enabling the parallel identification of multiple clinical pneumonia-related pathogens in 1.45-μL reactions without cross-contamination in 45 min. A portable nucleic acid analyzer that integrates mechanical, confocal optical, electronic, and software functions was also developed to collect fluorescence data in a Ø3 mm imaging field near the optical diffraction limit for highly sensitive fluorescence detection of nucleic acid amplification in real time. This microfluidic chip-based portable nucleic acid analyzer could detect low abundance nucleic acids present at as few as 10 copies. In a blinded experiment, specific identification of Mycoplasma pneumoniae, Staphylococcus aureus, and methicillin-resistant S. aureus was achieved with 229 clinical patient sputum samples. The total coincidence rate of our system and traditional RT-PCR with an ABI 7500 was 99.56%. Four samples accounting for the 0.44% inconformity were retested by gene sequencing, revealing that our system reported the correct results. This novel microfluidic chip-based detection system is cost-effective, rapid, sensitive, specific, and has a relatively high throughput for parallel identification, which is especially suitable for resource-limited facilities/areas and point-of-care testing.

Hazelnut is an important nut food that was widely consumed throughout prehistory. Archaeologists frequently find the charred plant macrofossils of Corylus at archaeological sites throughout Eurasia. We present new records of charred Siberian hazelnut ( Corylus heterophylla ) that were recovered from the Beiniu site (109.32°E, 34.46°N) in Shaanxi Province, North West China, that are directly dated around 5,400 cal. yr BP. They are basic evidence that we use to reconstruct the early history of hazelnut use in the northern part of China. Our findings in China are much less abundant than the hazelnut remains recovered at archaeological sites in Europe and North America. We suggest that the hazelnuts deposited in the cultural layer of Beiniu site were not intentionally used as a fuel but rather were first broken and then consumed as food before their eventual charring in a refuse pit. These discoveries also contribute to our understanding of risk mitigation strategies in food production by ancient farmers in China.

NLRC3, a member of the NLR family, has been reported as a negative regulator of inflammatory signaling pathways in innate immune cells. However, the direct role of NLRC3 in modulation of CD4+ T-cell responses in infectious diseases has not been studied. In the present study, we showed that NLRC3 plays an intrinsic role by suppressing the CD4+ T cell phenotype in lung and spleen, including differentiation, activation, and proliferation. NLRC3 deficiency in CD4+ T cells enhanced the protective immune response against Mycobacterium tuberculosis infection. Finally, we demonstrated that NLRC3 deficiency promoted the activation, proliferation, and cytokine production of CD4+ T cells via negatively regulating the NF-κB and MEK-ERK signaling pathways. This study reveals a critical role of NLRC3 as a direct regulator of the adaptive immune response and its protective effects on immunity during M. tuberculosis infection. Our findings also suggested that NLRC3 serves as a potential target for therapeutic intervention against tuberculosis.

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.

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.

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.

Hepatitis C virus (HCV) infection is associated with insulin resistance (IR) and type 2 diabetes (T2D). Chronic HCV patients with IR and T2D appear to have a decreased response to the standard pegylated-interferon-alpha and ribavirin (PEG-IFN/RBV) anti-viral therapy. Insulin and metformin are anti-diabetic drugs regularly used in the clinic. A previous in vitro study has shown a negative effect of insulin on interferon signaling. In the clinic, adding metformin to PEG-IFN/RBV therapy was reported to increase the response rate in chronic HCV patients and it has been suggested this effect derives from an improved anti-viral action of interferon. The goal of this study was to further investigate the molecular insight of insulin and metformin interaction with HCV infection and the anti-viral action of interferon. We used two cell culture models of HCV infection. One is a sub-genomic model that assays viral replication through luciferase reporter gene expression. The other one is a full-length infectious model derived from the JFH1 genotype 2a isolate. We found that both insulin and metformin do not affect HCV infection. Insulin and metformin also do not influence the anti-viral potency of interferon. In addition, there is no direct interaction between these two drugs and interferon signaling. Our results do not confirm the previous laboratory observation that insulin interferes with interferon signaling and suggest that classical nutritional signaling through mTOR may be not involved in HCV replication. If metformin indeed can increase the response rate to interferon therapy in patients, our data indicate that this could be mediated via an indirect mechanisms.

Pollen samples from peat sediments on the south bank of the Heilongjiang River in northern Northeast China (NE China) were analyzed to reconstruct the historical response of vegetation to climate change since 7800 cal yr BP. Vegetation was found to have experienced five successions from cold-temperate mixed coniferous and broadleaved forest to forest-steppe, steppe-woodland, steppe, and finally meadow-woodland. From 7800 to 7300 cal yr BP, the study area was warmer than present, and Betula, Larix, and Picea-dominated mixed coniferous and broadleaved forests thrived. Two cooling events at 7300 cal yr BP and 4500 cal yr BP led to a decrease in Betula and other broadleaved forests, whereas herbs of Poaceae expanded, leading to forest-steppe and then steppe-woodland environments. After 2500 cal yr BP, reduced temperatures and a decrease in evaporation rates are likely to have resulted in permafrost expansion and surface ponding, with meadow and isolated coniferous forests developing a resistance to the cold-wet environment. The Holocene warm period in NE China (7800–7300 cal yr BP) could have resulted in a strengthening of precipitation in northernmost NE China and encouraged the development of broadleaved forests.

Located on the Pamir Plateau in Xinjiang Province, China, the Ji'erzankale Necropolis dates back to 2500 yr BP. Many materials that have been unearthed in this cemetery, including shoo konghou (musical instrument), bronze mirrors and glass beads, suggest cultural transference between East and West. Furthermore, small-sized and rounded fire altars made from sweet-scented Sabina were found for the first time and regarded as implements for fire veneration. We identified 70 wooden objects from 25 tombs within the Necropolis, and found that each object had been made from one of seven tree species. Analysis revealed that the inhabitants of the region mainly used the most widely available types of wood, namely Betula and Populus. People also specifically chose inflammable Populus wood to make hearth boards and hand drills (both are used for making fire by drilling), rigid Betula wood to craft wooden plates. Salix was used for fashioning wooden sticks, while sweet-scented Sabina was the preferred choice for making fire altars. Lonicera was selected for arrow shaft manufacture and Fraxinus syriaca, which has a beautiful grain, was chosen for making musical instruments. Conscious selection of different types of wood indicates that people of the Pamir Plateau were aware of the properties of various types of timbers, and were able to exploit these properties to the full. In turn, this demonstrates their wisdom and their ability to survive in, and adapt to, their local environment.

In the new era, there is an urgent need to further promote pairing assistance to Tibet, promote the simultaneous construction of a strong agriculture in China, and compose a Chinese-style modernization. Southern Tibet, located in the southeastern part of the Tibet Autonomous Region, includes Shannan City and Nyingchi City, is a region assisted by four provincial partners including Hubei Province. This paper introduces the agricultural environment in southern Tibet, studies its agricultural characteristics, and analyzes the main issues of its pairing assistance. Taking forging the strong consciousness of the Chinese national community as the main line, the paper explores strategies for promoting agricultural high-quality development in southern Tibet through pairing assistance to Tibet from the perspective of agricultural power, and proposes some strategies, such as inheriting agricultural cultural heritage, promoting the upgrading of modern seed industry, enhancing the characteristic advantages of highland barley (naked barley) and animal husbandry industries, and developing edible fungi and cold water fish industries. [ABSTRACT FROM AUTHOR]

Due largely to demographic growth, agricultural populations during the Holocene became increasingly more impactful ecosystem engineers. Multidisciplinary research has revealed a deep history of human-environmental dynamics; however, these pre-modern anthropogenic ecosystem transformations and cultural adaptions are still poorly understood. Here, we synthesis anthracological data to explore the complex array of human-environmental interactions in the regions of the prehistoric Silk Road. Our results suggest that these ancient humans were not passively impacted by environmental change, but rather they culturally adapted to, and in turn altered, arid ecosystems. Underpinned by the establishment of complex agricultural systems on the western Loess Plateau, people may have started to manage chestnut trees, likely through conservation of economically significant species, as early as 4600 BP. Since ca. 3500 BP, with the appearance of high-yielding wheat/barley farming in Xinjiang and the Hexi Corridor, people appear to have been cultivating Prunus and Morus trees. We also argue that people were transporting the preferred coniferous woods over long distance to meet the need for fuel and timber. After 2500 BP, people in our study area were making conscious selections between wood types for craft production, and were also clearly cultivating a wide range of long-generation perennials, showing a remarkable traditional knowledge tied into the arid environment. At the same time, the data suggest that there was significant deforestation throughout the chronology of occupation, including a rapid decline of slow-growing spruce forests and riparian woodlands across the northwest China. The wood charcoal dataset is publicly available at https://doi.org/10.5281/zenodo.8158277 (Shen et al., 2023). [ABSTRACT FROM AUTHOR]