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Soil nematodes are among the most significant soil-dwelling organisms in forest ecosystems. However, the factors that shape the distribution of soil nematodes are still not well explored. Therefore, we collected soil samples from 20 forest sites along the eastern transect of China and sequenced 18S rRNA V9 region to reveal the biodiversity of soil nematodes. Our study found that soil nematode richness is higher in temperate mixed needleleaf and broadleaf forests compared with the other four vegetation regions. Soil physiochemical properties overrode climatic factors to be the primary drivers of soil nematode richness and community composition. Importantly, the soil nematode richness significantly enhanced ecosystem multifunctionality, especially bacterial biomass and enzyme activities, with a determination coefficient (r2) of 0.23, suggesting that soil nematodes played essential roles in the forest ecosystem.

Maize residue retention is an effective agricultural practice for improving soil fertility in black soil region, where suffered from long freezing-thawing periods and intense freeze-thawing (FT) cycles. However, very few studies have examined the influence of maize residue retention on soil microbial communities under FT cycles. We investigated the response of soil microbial communities and co-occurrence networks to maize residue retention at different FT intensities over 12 cycles using a microcosm experiment conditioned in a temperature incubator. Our results indicated that maize residue retention induced dramatic shifts in soil archaeal, bacterial and fungal communities towards copiotroph-dominated communities. Maize residue retention consistently reduced soil fungal richness across all cycles, but this effect was weaker for archaea and bacteria. Normalized stochastic ratio analysis revealed that maize residue retention significantly enhanced the deterministic process of archaeal, bacterial and fungal communities. Although FT intensity significantly impacted soil respiration, it did not induce profound changes in soil microbial diversity and community composition. Co-occurrence network analysis revealed that maize residue retention simplified prokaryotic network, while did not impact fungal network complexity. The network robustness index suggested that maize residue retention enhanced the fungal network stability, but reduced prokaryotic network stability. Moreover, the fungal network in severe FT treatment harbored the most abundant keystone taxa, mainly being cold-adapted fungi. By identifying modules in networks, we observed that prokaryotic Module #1 and fungal Module #3 were enhanced by maize residue retention and contributed greatly to soil quality. Together, our results showed that maize residue retention exerted stronger influence on soil microbial communities and co-occurrence network patterns than FT intensity and highlighted the potential of microbial interactions in improving soil functionality.

ABSTRACT The replant problem is a widespread challenge in agricultural production and results in significant financial losses. The survival and development of American ginseng (Panax quinquefolius L.), a well-known perennial medicinal plant, also typically suffer from replant problems. At present, efficient strategies for this issue and the underlying mechanisms are still lacking. Here, a series of in situ field experiments over a 4-year period were conducted to investigate the effectiveness and possible mechanisms of soil fumigation and fungicide in improving American ginseng survival under continuous cropping. During the 4-year ginseng cultivation, the seedling emergence rates in the dazomet fumigation-treated group (DF) decreased from 90.67% to 52.92%, from 78.67% to 0% in the lime sulfur fungicide-treated group (LS), and from 66.67% to 0% in the control. The fresh root weight in DF increased from 0.36 to 28.72 g, from 0.32 to 13.74 g in LS, and from 0.42 to 9.06 g in the control for the first 2 years. However, no ginseng survived during the following 2 years. Moreover, DF significantly decreased root rot disease incidence by 55.55% compared to LS-treated soil and 69.39% compared to non-treated soil. The correlation analysis results showed that both diversity and structure indices of bacteria and fungi were significantly correlated with root biomass and disease incidence in the second year. In summary, DF has presented a significant beneficial effect on American ginseng development. Additionally, the second year is the critical period to shape the soil microbial community, which could have a long-lasting effect on the development of American ginseng. IMPORTANCE Numerous reports of soil fumigants and fungicides on annual crops exist; however, it is unclear whether the single application to perennial plants persistently improves plant growth and controls disease or whether it has a long-lasting impact on soil microbes. We found that soil fumigation enhances ginseng growth and suppresses root rot disease by reshaping the soil microbial community. Our findings benefit the agricultural development of ginseng and provide a theoretical basis for the prevention of ginseng diseases.

H19 is an essential imprinted gene that is expressed to govern normal embryonic development. During reprogramming, the parental pronuclei have asymmetric reprogramming capacities and the critical reprogramming factors predominantly reside in the male pronucleus. After inhibiting the expression of H19 and Gtl2, androgenetic haploid ESCs (AG-haESCs) can efficiently and stably support the generation of healthy SC pups at a rate of ~20%, and double-knockout parthenogenetic haESCs can also produce efficiently. Induced pluripotent stem (iPS) cell reprogramming is thought to have a characteristic epigenetic pattern that is the reverse of its developmental potential; however, it is unclear how H19 participates in iPS cell reprogramming. Here, we showed that the expression of H19 was transiently increased during iPSC reprogramming. H19 knockdown resulted in greater reprogramming efficiency. The genes associated with pluripotency showed enhanced expression during the early reprogramming process, and the Oct4 promoter was demethylated by bisulfite genomic sequencing analysis. Moreover, expression analysis revealed that the mesenchymal master regulators associated with epithelial-to-mesenchymal transition (EMT) were downregulated during reprogramming in H19 knockdown. These findings provide functional insight into the role of H19 as a barrier to the early reprogramming process.

Abstract Background The nitrogenous compound deposited from the atmosphere to the soil is complex, but most field experiments mimic nitrogen deposition with the acid NH4NO3 alone. Thus, whether the acid and non-acid nitrogenous compounds have similar effects on biodiversity and ecosystem functions remains understudied. We mimicked nitrogen deposition with acidic NH4NO3 and (NH4)2SO4, and non-acidic urea, slow-released urea and NH4HCO3 in a temperate steppe, and quantified soil microbial taxonomic and functional gene composition with amplicon sequencing and shotgun metagenomics, respectively. Results While NH4NO3 and (NH4)2SO4 significantly altered the soil microbial taxonomic and functional composition as well as their carbon decomposition potential, the other three compounds had smaller effects. Conclusion Our results suggested that previous nitrogen deposition experiments mimicked with NH4NO3 or (NH4)2SO4 alone may have overestimated the effect on biodiversity and ecosystem functions in the Eurasian steppe and similar ecosystems affected by mainly nonacidic nitrogen deposition.

Cutaneous pigmentation was recently shown to be an event regulated by clock proteins. Cryptochrome (CRY) is a key protein composing the feedback loop of circadian clock, however, the function of CRY in melanocytes remains unclear. Here, we found that KL001, a synthetic small molecule modulator of CRY1, inhibited melanin synthesis, as well as reduced melanocyte dendrite elongation and melanosome transport. In addition, the dominant role of CRY1 in KL001-induced anti-melanogenesis was revealed by small interfering RNA transfection. Cellular tyrosinase activity and expression level of melanogenic proteins, including tyrosinase, TRP-1, TRP-2, and transport proteins like Rab27a, Cdc42 and Myosin Va induced by α-MSH were remarkably reversed after KL001 treatment. Mechanistically, CRY1 activation inhibited melanogenesis through CREB-dependent downregulation of MITF and CREB phosphorylation was mediated by classical cAMP/PKA pathway. In addition, the other CRY1 activator, KL044 also suppressed cAMP/PKA/CREB pathway and inhibited melanogenesis. Finally, anti-melanogenic efficacy of KL001 was confirmed by determination of melanin contents in UVB-tanning model of brown guinea pigs, which indicated that targeting CRY1 activity, via topical application of small molecule activator, can be utilized therapeutically to manage human pigmentary disorders.

Abstract Purpose Multiple anthropogenic disturbances, such as climate warming and nitrogen deposition are affecting terrestrial ecosystems. Different disturbances may have some consistent effects on the soil microbial community, which remains largely unexplored. Methods We mimicked 16 anthropogenic disturbances in a steppe ecosystem, and measured the absolute abundance and taxonomic composition of soil bacterial communities with qPCR and amplicon sequencing, respectively. Results We found that while the absolute abundance of each of the four dominant bacterial phyla did not show a consistent response to these disturbances, that of the five subdominant phyla showed a consistent increase. Meanwhile, these disturbances consistently stimulated the relative abundances of metabolic functions for high-growth-yield, including the transport/metabolism of amino acids and carbohydrates. Stochastic processes (e.g., random birth) played more critical roles in structuring the subdominant than dominant phyla, and the disturbances promoted the stochastic processes. Conclusions Overall, the high-yield traits and stochasticity of subdominant phyla led to their positive responses to disturbances. Furthermore, our findings indicate that the intensifying human activities are likely to cause a high-yield-strategies-toward shift in soil microbial composition in the Eurasian steppe ecosystem.

Summary: Precipitation may increase or decrease by different intensities, but the pattern and mechanism of soil microbial community assembly under various precipitation changes remain relatively underexplored. Here, although ±30% precipitation caused a small decrease (∼19%) in the within-treatment taxonomic compositional dissimilarity through the deterministic competitive exclusion process in a steppe ecosystem, ±60% precipitation caused a large increase (∼35%) in the dissimilarity through the stochastic ecological drift process (random birth/death), which was in contrast with the traditional thought that increasing the magnitude of environmental changes (e.g., from +30% to +60%) would elevate the importance of deterministic relative to stochastic processes. The increased taxonomic dissimilarity/stochasticity under ±60% precipitation translated into functional dissimilarity/stochasticity at the gene, protein, and enzyme levels. Overall, our results revealed the distinctive pattern and mechanism of precipitation changes affecting soil microbial community assembly and demonstrated the need to integrate microbial taxonomic information to better predict their functional responses to precipitation changes.

American ginseng (Panax quinquefolius L.) is a perennial medicinal plant that has a long usage history in China. However, root rot, which is mainly caused by Fusarium solani can severely reduce the yield and quality of American ginseng, but no disease-resistant variety of American ginseng exists, and the resistance against this disease is not yet well understood. Thus, it is very urgent to analyze the interaction mechanism regulating the interactions between American ginseng and F. solani to mine disease resistance genes. Using transcriptome data and quantitative polymerase chain reaction (qPCR), we screened the transcription factor PqbZIP1 in response to induction by chitin. Yeast self-activation and subcellular localization experiments proved that PqbZIP1 showed transcriptional activity and was localized in the plant nucleus. In addition, qPCR showed that the highest relative expression level was in the roots, wherein chitin and F. solani inhibited and activated the expression of PqbZIP1, respectively, in American ginseng. Additionally, PqbZIP1 significantly inhibited the growth of the Pseudomonas syringae pv. tomato D36E strain in Nicotiana benthamiana, where expressing PqbZIP1 in N. benthamiana increased the jasmonic acid, salicylic acid, and abscisic acid content. Furthermore, PqbZIP1 expression was continually increased upon inoculation with F. solani. Hence, this study revealed that the PqbZIP1 transcription factor might mediate multiple hormonal signaling pathway to modulate root rot disease resistance in American ginseng, and provided important information to breed disease-resistant American ginseng.

Soil microbes are an essential component of terrestrial ecosystems and drive many biogeochemical processes throughout the soil profile. Prior field studies mainly focused on the vertical patterns of soil microbial communities, meaning their temporal dynamics have been largely neglected. In the present study, we investigated the vertical and temporal patterns of soil bacterial and archaeal communities in a wheat-soybean rotation agroecosystem at a depth of millions of sequences per sample. Our results revealed different vertical bacterial and archaeal richness patterns: bacterial richness was lowest in the deep soil layer and peaked in the surface or middle soil layer. In contrast, archaeal richness did not differ among soil layers. PERMANOVA analysis indicated that both bacterial and archaeal community compositions were significantly impacted by soil depth but unaffected by sampling time. Notably, the proportion of rare bacteria gradually decreased along with the soil profile. The rare bacterial community composition was the most important indicator for soil nutrient fertility index, as determined by random forest analysis. The soil prokaryotic co-occurrence networks of the surface and middle soil layers are more connected and harbored fewer negative links than that of the deep soil layer. Overall, our results highlighted soil depth as a more important determinant than temporal variation in shaping the soil prokaryotic community and interspecific interactions and revealed a potential role of rare taxa in soil biogeochemical function.

Abstract Background To describe the clinical characteristics and analyze the predictive factors associated with improved visual acuity of 359 patients with infectious endophthalmitis. Methods This study retrospectively analyzed 359 eyes of 359 patients with infectious endophthalmitis from January 2014 to December 2018. The findings summarized some epidemiological characteristics of these patients, including age, sex, occupation, patient visit time, etiology, causative organisms, therapy, and best-corrected visual acuity. Multivariate logistic regression was performed to predict the relative factors of improved visual acuity (VA). Results Overall, 283 (78.83%) patients were male. The mean age was 48.0 ± 18.27 years. Ocular trauma, especially open globe injuries (246, 68.5%) was the most common etiology of infectious endophthalmitis in this study. The etiologies of infectious endophthalmitis were open globe injuries (68.5%), intraocular surgery (22.6%), and corneal ulcer-associated (6.7%) and endogenous causes (2.2%). In the etiology classification and visual acuity improvement group, had statistically significant differences in factors such as age, sex, patient visit time, pre-therapy visual acuity, etc. The average Logarithm of the Minimum Angle of Resolution (logMAR) best-corrected visual acuity on pre-therapy was 2.28 ± 0.60, and it had significantly improved to 1.67 ± 0.83 post-therapy (P 7 day (P = 0.034, OR = 0.522, 95% CI: 0.286–0.953), pre-therapy VA ≦logMAR 2.3 (P = 0.032, OR = 1.809, 95% CI: 1.052–3.110), post-surgical (vs. posttraumatic; P = 0.023, OR = 2.100, 95% CI: 1.109–3.974), and corneal ulcer-associated etiologies (vs. posttraumatic; P = 0.005, OR = 0.202, 95%CI: 0.066–0.621) were significantly associated with improved visual acuity after adjusting for possible confounding factors. Conclusions Among the patients with infectious endophthalmitis, middle-aged male, especially farmers and workers, accounted for a large proportion. Open globe injuries were the main cause and the gram-positive bacteria were the major causative organisms. The final visual outcomes seemed to vary according to the type of endophthalmitis, but early treatment and good initial visual acuity were important factors for visual acuity improvement.

Abstract Background The aim of this study was to investigate the role of long non-coding RNA (lncRNA) H19 in gastric cancer (GC) with Helicobacter pylori (H. pylori). Methods H19 expression in peripheral blood from H. pylori+/− GC patients and healthy donors (control) as well as in GC tissues and cells were detected by qRT-PCR. Cell proliferation was evaluated by CCK-8 assay. Cell migration and invasion were evaluated by Transwell assay. The levels of pro-inflammatory cytokines were determined by ELISA. The protein levels of IκBα, p-IκBα and p65 were determined by western blotting. Results H19 expression was upregulated in H. pylori-infected GC tissues and cells. Furthermore, H. pylori promoted GC cell viability, migration, invasion and inflammatory response. Moreover, H19 overexpression promoted the proliferation, migration and invasion of H. pylori-infected GC cells via enhancing NF-κB-induced inflammation. Conclusions LncRNA H19 promotes H. pylori-induced GC cell growth via enhancing NF-κB-induced inflammation.

It is a central goal of current community ecology to explore the pattern and mechanism of community response to anthropogenic disturbances. Most researches focus on the response of community composition, which is based on the presence/absence or relative abundances of different species. However, the response of species-identity-independent community structure, such as the rank-abundance distribution, remains relatively understudied. We conducted a ten-year nitrogen addition experiment in a temperate steppe, with nine nitrogen rates under fencing (un-mowed) or mowing conditions. Mowing and nitrogen addition significantly altered both the composition and structure of plant communities. While the relative importance of stochastic change in community composition under mowing was not significantly different from that under fencing, the relative importance of stochastic change in community structure under mowing was significantly larger than that under fencing. Overall, our results demonstrated that mowing led to different drivers for the community composition and structure, meaning that mowing promoted the stochastic allocation of material and energy in primary producers in the grassland ecosystem.

The therapeutic use of curcumin and chemically modified curcumin (CMC) for suppressing melanogenesis and tyrosinase activity have been recognized. J147 is a modified version of curcumin with superior bioavailability and stability. However, there is no report about the effects of J147 on pigmentation in vitro and in vivo. In our studies, we investigated the hypopigmentary effects of J147 treatment on melanocytes and explored the underlying mechanism. The present studies suggested that J147 suppressed both basal and α-MSH-induced melanogenesis, as well as decreased melanocyte dendricity extension and melanosome transport. J147 played these roles mainly by activating the extracellular signal-regulated protein kinase (ERK) pathway. Once activated, it resulted in MITF degradation and further down-regulated the expression of tyrosinase, TRP-1, TRP-2, Myosin Va, Rab27a and Cdc42, ultimately inhibited melanin synthesis and melanosome transport. Furthermore, the hypopigmentary effects of J147 were demonstrated in vivo in a zebrafish model and UVB-induced hyperpigmentation model in brown guinea pigs. Our findings also suggested that J147 exhibited no cytotoxicity in vitro and in vivo. Taken together, these data confirmed that J147 may prove quite useful as a safer natural skin-whitening agent.

Compost and biochar are beneficial soil amendments which derived from agricultural waste, and their application was proven to be effective practices for promoting soil fertility. Arbuscular mycorrhizal (AM) fungi form symbiotic associations with most crop plant species, and are recognized as one group of the most important soil microorganisms to increase food security in sustainable agriculture. To understand the legacy effects of compost and biochar addition on AM fungal communities, a field study was conducted on the Songnen Plain, Northeast China. Two years after application, compost addition improved soil aggregate stability, but we did not detect a legacy effect of compost addition on AM fungal community. Our results indicated that AM fungal Shannon diversity and Pielou evenness indices were significantly increased by one-time biochar addition, but unaffected by compost addition after two year’s application. PERMANOVA analysis also revealed a legacy effect of biochar addition on AM fungal community. Network analysis revealed a dramatically simplified AM fungal co-occurrence network and small network size in biochar added soils, demonstrated by their topological properties (e.g., low connectedness and betweenness). However, AM fungal community did not differ among aggregate fractions, as confirmed by the PERMANOVA analysis as well as the fact that only a small number of AM fungal OTUs were shared among aggregate fractions. Consequently, the current study highlights a stronger legacy effect of biochar than compost addition on AM fungi, and have implications for agricultural practices.

Electrocardiogram (ECG) is an important tool for the detection of acute ST-segment elevation myocardial infarction (STEMI). However, machine learning (ML) for the diagnosis of STEMI complicated with arrhythmia and infarct-related arteries is still underdeveloped based on real-world data. Therefore, we aimed to develop an ML model using the Least Absolute Shrinkage and Selection Operator (LASSO) to automatically diagnose acute STEMI based on ECG features. A total of 318 patients with STEMI and 502 control subjects were enrolled from Jan 2017 to Jun 2019. Coronary angiography was performed. A total of 180 automatic ECG features of 12-lead ECG were input into the model. The LASSO regression model was trained and validated by the internal training dataset and tested by the internal and external testing datasets. A comparative test was performed between the LASSO regression model and different levels of doctors. To identify the STEMI and non-STEMI, the LASSO model retained 14 variables with AUCs of 0.94 and 0.93 in the internal and external testing datasets, respectively. The performance of LASSO regression was similar to that of experienced cardiologists (AUC: 0.92) but superior (p < 0.05) to internal medicine residents, medical interns, and emergency physicians. Furthermore, in terms of identifying left anterior descending (LAD) or non-LAD, LASSO regression achieved AUCs of 0.92 and 0.98 in the internal and external testing datasets, respectively. This LASSO regression model can achieve high accuracy in diagnosing STEMI and LAD vessel disease, thus providing an assisting diagnostic tool based on ECG, which may improve the early diagnosis of STEMI.

Northeast China is well known for cultivating ginseng (Panax ginseng and P. quinquefolius). Ginseng roots are threatened by the infection of the most notorious Cylindrocarpon-like fungi (CLF), which are a complex containing important soilborne pathogens. Although the disease is economically important, little is known about the genetic diversity and population structure of the pathogenic CLF complex. This knowledge will help in developing effective disease management strategies. To conduct this study, diseased ginseng roots were collected from 12 regions representing the main ginseng-growing areas in Northeast China, and CLF were isolated. A total of 169 isolates with CLF anamorph were identified in two Dactylonectria species and six Ilyonectria species using morphological and molecular methods. Cross pathogenicity tests showed that all species were pathogenic to both P. ginseng and P. quinquefolius, and most of them had slightly stronger aggressiveness in P. ginseng. The analysis of partial sequences of the Histone H3 gene generated a high level of genetic diversity and geographic differentiation. A total of 132 variable sites were detected in 169 sequences, which formed 20 haplotypes with a haplotype diversity of 0.824. Genetic differentiation was positively correlated with geographic distance. The geographic populations in the range of Changbai Mountain were distinctly discriminated from those in other non-Changbai Mountain populations. No significant genetic differentiation was found between ginseng hosts. Cylindrocarpon-like fungi causing ginseng root diseases are geographically correlated in the genetic distance in Northeast China and should be managed correspondingly.

Random migration often plays important roles in soil microbial community assembly. However, it remains unexplored that whether its role is affected by anthropogenic disturbances, and whether the effects of different disturbances are consistent. Here, we report a novel and general pattern that different disturbances consistently restrain the role of migration in soil bacterial community assembly. We mimicked 16 types of anthropogenic disturbances relevant to a Eurasian steppe ecosystem, including removing different number of plant functional groups, mowing, adding nitrogen, adding phosphorus, watering, warming, and some of their combinations. The estimated migration rates in soil bacterial community assembly with Stephen Hubbell’s neutral model decreased by 0.19–6.29% under these disturbances. The relative change in migration rate was correlated with the deterministic change in community composition and the relative change in soil pH. Our results suggested that the intensifying anthropogenic disturbances may restrain the random dispersal, colonization and distribution of soil microorganisms.

Increasing atmospheric nitrogen (N) deposition causes profound changes in the plant community, significantly threatening the terrestrial ecosystem function and stability worldwide. Random migration is a primary determinant of plant community assembly in the neutral model. However, whether its role is affected by N deposition is obscure. Therefore, the effects of eight N application rates (0, 1, 2, 3, 5, 10, 15, and 20 g N m−2 yr−1) on the estimated migration rate of plant community were examined in a long-term field study in a semiarid steppe. Our results indicated that N addition significantly impacted the estimated migration rate (F = 4.89, P

Abstract Background Mounting evidence has shown that a novel subset of mesenchymal stem cells (MSCs) derived from human gingiva referred to as gingival mesenchymal stem cells (GMSCs) displays a greater immunotherapeutic potential and regenerative repair expression than MSCs obtained from other tissues. However, the safety of the use of transplanted GMSCs in humans remains unclear. Methods In this study, we evaluated the safety of GMSCs transplanted into mouse, rat, rabbit, beagle dog, and monkey as well as two animal models of autoimmune diseases. Results In short- and long-term toxicity tests, infused GMSCs had no remarkable adverse effects on hematologic and biochemical indexes, particularly on the major organs such as heart, liver, spleen, and kidney in recipient animals. It was also shown that GMSCs were well tolerated in other assays including hemolysis, vascular, and muscular stimulation, as well as systemic anaphylaxis and passive skin Arthus reaction in animal models. GSMC infusion did not cause any notable side effects on animal models of either autoimmune arthritis or lupus. Significantly, GMSCs most likely play no role in genotoxicity and tumorigenesis. The biological features remained stable for an extended period after cell transfer. Conclusions GMSCs are safe in various animal models of autoimmunity, even during active disease episodes, especially in monkeys. This study paves a solid road for future clinical trials of GMSCs in patients with autoimmune and inflammatory diseases.

Background: Bone destruction is one of many severe complications that occurs in patients with rheumatoid arthritis (RA) and current therapies are unable to cure this manifestation. This study here aims to determine whether GMSC can directly inhibit osteoclast formation and eventually attenuate osteoclastogenesis and bone erosion in an inflammatory milieu. Method: GMSC were co-cultured with osteoclast precursors with or without CD39 inhibitor, CD73 inhibitor or adenosine receptors inhibitors pretreatment and osteoclast formation were evaluated in vitro. 2×10^6 GMSC per mouse were transferred to CIA mice and pathology scores, the frequency of osteoclasts, bone erosion in joints were assessed in vivo. Finding: GMSC but not control cells, markedly suppressed human or mice osteoclastogenesis in vitro. GMSC treatment also resulted in a dramatically decreased level of NF-κB p65/p50 in osteoclasts in vitro. Infusion of GMSC to CIA significantly attenuated the severity of arthritis, pathology scores, frequency of osteoclasts, particularly bone erosion, as well as a decreased expression of RANKL in synovial tissues in vivo. Blockade of CD39/CD73 or adenosine receptors has significantly abrogated the suppressive ability of GMSC in vitro and therapeutic effect of GMSC on bone erosion during CIA in vivo. Interpretation: GMSC inhibit osteoclast formation in vitro and in vivo partially via CD39-CD73-adenosine signals. Manipulation of GMSC may have a therapeutic implication on rheumatoid arthritis and other bone erosion related diseases. Fund: This study was supported by grants from the National Key R&D Program of China (2017YFA0105801 to F.H); the Zhujiang Innovative and Entrepreneurial Talent Team Award of Guangdong Province (2016 ZT 06S 252 to F·H) and National Institutes of Health (R01 AR059103, R61 AR073409 and NIH Star Award to S.G.Z). Keywords: Rheumatoid arthritis, Mesenchymal stem cells, CD39, Adenosine

Tillage practices and residue management are highly important agricultural practices. However, very few studies have examined the influence of tillage practices and residue management on both bacterial and fungal communities and network patterns in consecutive years. We examined the effects of different tillage practices, including no tillage, rotary tillage, and deep tillage, on soil bacterial and fungal communities and co-occurrence networks following residue removal and residue retention in 2017 and 2018. This study showed that both bacterial and fungal communities were unaffected by tillage practices in 2017, but they were significantly impacted in 2018. Soil fungal operational taxonomic unit (OTU) richness was significantly enhanced by deep tillage compared with no tillage in 2018, while bacterial OTU richness was unaffected in either year. Tillage practices had differing effects on soil microbial co-occurrence networks, with rotary and deep tillage increasing the complexity of bacterial networks but simplifying fungal networks. However, residue retention only induced a shift in the fungal community and simplified soil bacterial and fungal networks in 2018. This study highlights the dissimilar responses of bacterial and fungal networks to tillage practices and emphasizes that tillage practice is more important than residue management in shaping soil microbial communities.

FGIN-1-27 is a synthetic mitochondrial diazepam binding inhibitor receptor (MDR) agonist that has demonstrated pro-apoptotic, anti-anxiety, and steroidogenic activity in various studies. Here we report, for the first time, the anti-melanogenic efficacy of FGIN-1-27 in vitro and in vivo. FGIN-1-27 significantly inhibited basal and α-melanocyte-stimulating hormone (α-MSH)-, 1-Oleoyl-2-acetyl-sn-glycerol (OAG)- and Endothelin-1 (ET-1)-induced melanogenesis without cellular toxicity. Mushroom tyrosinase activity assay showed that FGIN-1-27 did not directly inhibit tyrosinase activity, which suggested that FGIN-1-27 was not a direct inhibitor of tyrosinase. Although it was not capable of modulating the catalytic activity of mushroom tyrosinase in vitro, FGIN-1-27 downregulated the expression levels of key proteins that function in melanogenesis. FGIN-1-27 played these functions mainly by suppressing the PKA/CREB, PKC-β, and MAPK pathways. Once inactivated, it decreased the expression of MITF, tyrosinase, TRP-1, TRP-2, and inhibited the tyrosinase activity, finally inhibiting melanogenesis. During in vivo experiments, FGIN-1-27 inhibited the body pigmentation of zebrafish and reduced UVB-induced hyperpigmentation in guinea pig skin, but not a reduction of numbers of melanocytes. Our findings indicated that FGIN-1-27 exhibited no cytotoxicity and inhibited melanogenesis in both in vitro and in vivo models. It may prove quite useful as a safer skin-whitening agent.

Understanding species responsiveness to anthropogenic environmental changes benefits the guide to manage biodiversity. Microbes are traditionally thought to be more sensitive to environmental changes than plants. However, this hypothesis is supported by little empirical evidence. We compared plant and microbial responses to 13 types of simulated environmental changes (mowing (M), adding nitrogen (N), adding phosphorus (P), watering (W), warming (T) and combinations of these) in a steppe ecosystem. Contrary to our hypothesis, the microbial responses were generally smaller than the plant responses to different types of environmental changes, both at the community-abundance level and species/operational taxonomic unit (OTU)/gene level. This might be ascribed to the soil buffering capacity to environmental changes, and the rapid evolutionary adaptation for microbial communities. Furthermore, the responses at the community-abundance level were larger than at the species/OTU/gene level to 13 types of environmental changes, both in plant and microbial communities. Given that the community abundance representing the total number of all individuals of the organism within the community, the responses to environmental changes at the community-abundance level is likely to be larger than at the species/OTU/gene level. Plant biomass was more responsive to N addition, particularly in such N- limiting grassland ecosystem. Our findings highlight that plant communities are more responsive to environmental changes than microbial communities, contrary to the traditional viewpoint. Therefore, plant communities could be used as ecological indicators of anthropogenic environmental changes in grasslands. Keywords: Plant community, Microbial community, Anthropogenic environmental changes, Grassland, Abundance, Species/OTU/Gene number

ABSTRACT It is a central ecological goal to explore the effects of global change factors on soil microbial communities. The vast functional gene repertoire of soil microbial communities is composed of both core and accessory genes, which may be governed by distinct drivers. This intuitive hypothesis, however, remains largely unexplored. We conducted a 5-year nitrogen and water addition experiment in the Eurasian steppe and quantified microbial gene diversity via shotgun metagenomics. Nitrogen addition led to an 11-fold increase in the abundance (based on quantitative PCR [qPCR]) of ammonia-oxidizing bacteria, which have mainly core community genes and few accessory community genes. Thus, nitrogen addition substantially increased the relative abundance of many core genes at the whole-community level. Water addition stimulated both plant diversity and microbial respiration; however, increased carbon/energy resources from plants did not counteract increased respiration, so soil carbon/energy resources became more limited. Thus, water addition selected for microorganisms with genes responsible for degrading recalcitrant soil organic matter. Accordingly, many other microorganisms without these genes (but likely with other accessory community genes due to relatively stable average microbial genome size) were selected against, leading to the decrease in the diversity of accessory community genes. In summary, nitrogen addition primarily affected core community genes through nitrogen-cycling processes, and water addition primarily regulated accessory community genes through carbon-cycling processes. Although both gene components may significantly respond as the intensity of nitrogen/water addition increases, our results demonstrated how these common global change factors distinctly impact each component. IMPORTANCE Our results demonstrated increased ecosystem nitrogen and water content as the primary drivers of the core and accessory components of soil microbial community functional diversity, respectively. Our findings suggested that more attention should be paid to certain components of community functional diversity under specific global change conditions. Our findings also indicated that microbial communities have adapted to nitrogen addition by strengthening the function of ammonia oxidization to deplete the excess nitrogen, thus maintaining ecosystem homeostasis. Because community gene richness is primarily determined by the presence/absence of accessory community genes, our findings further implied that strategies such as maintaining the amount of soil organic matter could be adopted to effectively improve the functional gene diversity of soil microbial communities subject to global change factors.

Atherosclerosis is the major cause of cardiovascular diseases. Current evidences indicate that inflammation is involved in the pathogenesis of atherosclerosis. Human gingiva-derived mesenchymal stem cells (GMSC) have shown anti-inflammatory and immunomodulatory effects on autoimmune and inflammatory diseases. However, the function of GMSC in controlling atherosclerosis is far from clear. The present study is aimed to elucidate the role of GMSC in atherosclerosis, examining the inhibition of GMSC on macrophage foam cell formation, and further determining whether GMSC could affect the polarization and activation of macrophages under different conditions. The results show that infusion of GMSC to AopE−/− mice significantly reduced the frequency of inflammatory monocytes/macrophages and decreased the plaque size and lipid deposition. Additionally, GMSC treatment markedly inhibited macrophage foam cell formation and reduced inflammatory macrophage activation, converting inflammatory macrophages to anti-inflammatory macrophages in vitro. Thus, our study has revealed a significant role of GMSC on modulating inflammatory monocytes/macrophages and alleviating atherosclerosis.

Impact of soil water regimes on physiological responses and water use efficiency (WUE) for Vigna unguiculata L. Walp. (cowpea) inoculated with rhizobia still remains implicit. Therefore, the goal of the current study was to examine the leaf gas exchange, abscisic acid (ABA) and hydraulic signaling, WUE and carbon and oxygen isotopic compositions (δ13C and δ18O) of cowpea under different soil water levels. The treatments included soil water regimes at three levels (90%, 70%, and 50% of soil water holding capacity (SWHC)) and two inoculation forms (inoculated and non-inoculated with rhizobia). The results showed that across the inoculation treatments, reduced soil water regimes depressed both stomatal conductance (gs) and photosynthesis (An) of the leaves, nonetheless, the decrease of gs was more pronounced compared with the reduction in An. Consequently, the intrinsic water use efficiency (WUEi) was improved in the treatments under decreased soil water conditions. Plant WUE was also improved when soil water contents decreased as exemplified by the increased leaf δ13C and δ18O, indicating the enhanced plant WUE was mainly attributed to the decrease of gs. Significant interactions between soil water regimes and rhizobia treatments for root water potential (RWP), leaf water potential (LWP), and gs were found due to the different responses of rhizobia to varied soil water regimes. Inoculation could improve plant water status and gs under 70% and 90% SWHC compared to 50% SWHC with negative effect from rhizobia. A moderate soil water regime is suggested for cowpea production in terms of high WUE with a minor biomass reduction.

Nitrogen (N) and phosphorus (P) are important limiting nutrients for plant production and consumer performance in a variety of ecosystems. As a result, the N:P stoichiometry of herbivores has received increased attention in ecology. However, the mechanisms by which herbivores maintain N:P stoichiometric homeostasis are poorly understood. Here, using a field manipulation experiment we show that the grasshopper Oedaleus asiaticus maintains strong N:P stoichiometric homeostasis regardless of whether grasshoppers were reared at low or high density. Grasshoppers maintained homeostasis by increasing P excretion when eating plants with higher P contents. However, while grasshoppers also maintained constant body N contents, we found no changes in N excretion in response to changing plant N content over the range measured. These results suggest that O. asiaticus maintains P homeostasis primarily by changing P absorption and excretion rates, but that other mechanisms may be more important for regulating N homeostasis. Our findings improve our understanding of consumer-driven P recycling and may help in understanding the factors affecting plant-herbivore interactions and ecosystem processes in grasslands.

Many investigations across natural and artificial plant diversity gradients have reported that both soil physicochemical factors and plant community composition affect soil microbial communities. To test the effect of plant diversity loss on soil bacterial communities, we conducted a five-year plant functional group removal experiment in a steppe ecosystem in Inner Mongolia (China). We found that the number and composition type of plant functional groups had no effect on bacterial diversity and community composition, or on the relative abundance of major taxa. In contrast, bacterial community patterns were significantly structured by soil water content differences among plots. Our results support researches that suggest that water availability is the key factor structuring soil bacterial communities in this semi-arid ecosystem.

Climate warming and shifting precipitation regimes are affecting biodiversity and ecosystem functioning. Most studies have focused on the influence of warming and altered precipitation on macro-organisms, whereas the responses of soil microbial communities have been neglected. We studied the changes in the abundance, richness, and composition of the entire bacterial kingdom and 16 dominant bacterial phyla/classes in response to increased precipitation, warming, and their combination, by conducting a 5-year experiment in a steppe ecosystem in Inner Mongolia, China. Watering had a greater effect than warming on almost all the bacterial groups as indicated by changes in all the three attributes (abundance, richness, and composition). The 16 phyla/classes responded differentially to the experimental treatments, with Acidobacteria and Gamma-proteobacteria being the most sensitive. Stepwise regression analyses further revealed that climate changes altered the abundance and richness of bacterial groups primarily through direct routes (e.g., increasing soil water content), and changed the community composition through both direct and indirect routes (e.g., reducing soil total nitrogen content and increasing soil pH). The diverse responses of various bacterial groups could imply some potential shift in their ecosystem functions under climate changes; meanwhile, the indirect routes that are important in altering bacterial composition suggest that specific strategies (e.g., adding NH4NO3 to maintain soil nitrogen content and pH) could be adopted to maintain soil microbial composition under climate changes.

In many grassland ecosystems, nitrogen (N) and phosphorus (P) are added to improve plant productivity, and the aboveground plant biomass is mowed and stored as hay for the bullamacow. Nutrient addition and mowing affect the biodiversity and ecosystem functioning, and most of the previous studies have primarily focused on their effects on macro-organisms, neglecting the responses of soil microbial communities. In this study, we examined the changes in three community attributes (abundance, richness, and composition) of the entire bacterial kingdom and 16 dominant bacterial phyla/classes in response to mowing, N addition, P addition, and their combinations, by conducting a 5-year experiment in a steppe ecosystem in Inner Mongolia, China. Overall, N addition had a greater effect than mowing and P addition on most of these bacterial groups, as indicated by changes in the abundance, richness and composition in response to these treatments. N addition affected these soil bacterial groups primarily through reducing soil pH and increasing available N content. Meanwhile, the 16 bacterial phyla/classes responded differentially to these experimental treatments, with Acidobacteria, Acidimicrobidae, Deltaproteobacteria, and Gammaproteobacteria being the most sensitive. The changes in the abundance, richness, and composition of various bacterial groups could imply some potential shift in their ecosystem functions. Furthermore, the important role of decreased soil pH caused by N addition in affecting soil bacterial communities suggests the importance of restoring acidified soil to maintain soil bacterial diversity.

Multiple co-occurring environmental changes are affecting soil nitrogen cycling processes, which are mainly mediated by microbes. While it is likely that various nitrogen-cycling functional groups will respond differently to such environmental changes, very little is known about their relative responsiveness. Here we conducted four long-term experiments in a steppe ecosystem by removing plant functional groups, mowing, adding nitrogen, adding phosphorus, watering, warming, and manipulating some of their combinations. We quantified the abundance of seven nitrogen-cycling genes, including those for fixation (nifH), mineralization (chiA), nitrification (amoA of ammonia-oxidizing bacteria (AOB) or archaea (AOA)), and denitrification (nirS, nirK and nosZ). First, for each gene, we compared its sensitivities to different environmental changes and found that the abundances of various genes were sensitive to distinct and different factors. Overall, the abundances of nearly all genes were sensitive to nitrogen enrichment. In addition, the abundances of the chiA and nosZ genes were sensitive to plant functional group removal, the AOB-amoA gene abundance to phosphorus enrichment when nitrogen was added simultaneously, and the nirS and nirK gene abundances responded to watering. Second, for each single- or multi-factorial environmental change, we compared the sensitivities of the abundances of different genes and found that different environmental changes primarily affected different gene abundances. Overall, AOB-amoA gene abundance was most responsive, followed by the two denitrifying genes nosZ and nirS, while the other genes were less sensitive. These results provide, for the first time, systematic insights into how the abundance of each type of nitrogen-cycling gene and the equilibrium state of all these nitrogen-cycling gene abundances would shift under each single- or multi-factorial global change.

Oxidative stress in adipose tissue plays an etiological role in a variety of obesity-related metabolic disorders. We previously reported that increased adipose tissue 4-hydroxynonenal (4-HNE) contents contributed to obesity-related plasma adiponectin decline in mice. In the present study, we investigated the effects of intracellular 4-HNE accumulation on lipolytic response in adipocytes/adipose tissues and underlying mechanisms. In both fully-differentiated 3T3-L1 and primary adipocytes, a 5-hour 4-HNE exposure elevated lipolytic reaction in a dose-dependent manner at both basal and isoproterenol-stimulated conditions, evidenced by significantly increased glycerol and fatty acids releases. This conclusion was corroborated by the comparable observations when the minced human visceral adipose tissues were used. Mechanistic investigations revealed that 4-HNE-stimulated lipolytic activation is multifactorial. 4-HNE exposure quickly increased intracellular cyclic AMP (cAMP) level, which was concomitant with increased phosphorylations of protein kinase A (PKA) and its direct downstream target, hormone sensitive lipase (HSL). Pre-incubation with H89, a potent PKA inhibitor, prevented 4-HNE stimulated glycerol release, suggesting that enhanced lipolytic action in response to 4-HNE increase is mediated mainly by cAMP/PKA signal pathway in adipocytes. In addition to activating cAMP/PKA/HSL pathway, 4-HNE exposure also suppresses AMP-activated protein kinase (AMPK), a suppressive pathway for lipolysis, measured by both Western blotting for phosphorylated form of AMPK and ELISA for enzyme activity. Furthermore, 5-Aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside (AICAR), a pharmacological AMPK activator, alleviated 4-HNE-induced lipolysis, suggesting that AMPK suppression also contributes to 4-HNE elicited lipolytic response. In conclusion, our findings indicate that increased intracellular 4-HNE accumulation in adipocytes/adipose tissues contributes to obesity-related lipolytic activation.