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Proper regulation of p53 signaling is critical for the maintenance of hematopoietic stem cells (HSCs) and leukemic stem cells (LSCs). The hematopoietic cell–specific mechanisms regulating p53 activity remain largely unknown. Here, we demonstrate that conditional deletion of acidic leucine-rich nuclear phosphoprotein 32B (ANP32B) in hematopoietic cells impairs repopulation capacity and postinjury regeneration of HSCs. Mechanistically, ANP32B forms a repressive complex with p53 and thus inhibits the transcriptional activity of p53 in hematopoietic cells, and p53 deletion rescues the functional defect in Anp32b-deficient HSCs. Of great interest, ANP32B is highly expressed in leukemic cells from patients with chronic myelogenous leukemia (CML). Anp32b deletion enhances p53 transcriptional activity to impair LSC function in a murine CML model and exhibits synergistic therapeutic effects with tyrosine kinase inhibitors in inhibiting CML propagation. In summary, our findings provide a novel strategy to enhance p53 activity in LSCs by inhibiting ANP32B and identify ANP32B as a potential therapeutic target in treating CML.

Microbes are decomposers of crop residues, and climatic factors and residue composition are known to influence microbial growth and community composition, which in turn regulate residue decomposition. However, the succession of the bacterial community during residue decomposition in Northeast China is not well understood. To clarify the property of bacterial community succession and the corresponding factors regulating this succession, bags containing maize residue were buried in soil in Northeast China in October, and then at different intervals over the next 2 years, samples were analyzed for residue mass and bacterial community composition. After residue burial in the soil, the cumulative residue mass loss rates were 18, 69, and 77% after 5, 12, and 24 months, respectively. The release of residue nitrogen, phosphorus, and carbon followed a similar pattern as mass loss, but 79% of residue potassium was released after only 1 month. The abundance, richness, and community diversity of bacteria in the residue increased rapidly and peaked after 9 or 20 months. Residue decomposition was mainly influenced by temperature and chemical composition in the early stage, and was influenced by chemical composition in the later stage. Phyla Actinobacteria, Bacteroidetes, and Firmicutes dominated the bacterial community composition in residue in the early stage, and the abundances of phyla Chloroflexi, Acidobacteria, and Saccharibacteria gradually increased in the later stage of decomposition. In conclusion, maize residue decomposition in soil was greatly influenced by temperature and residue composition in Northeast China, and the bacterial community shifted from dominance of copiotrophic populations in the early stage to an increase in oligotrophic populations in the later stage.

Poly(ADP-ribosyl)ation (PARylation) is a posttranslational modification reversibly catalyzed by poly(ADP-ribose) polymerases (PARPs) and poly(ADP-ribose) glycohydrolases (PARGs) and plays a key role in multiple cellular processes. The molecular mechanisms by which PARylation regulates innate immunity remain largely unknown in eukaryotes. Here we show that Arabidopsis UBC13A and UBC13B, the major drivers of lysine 63 (K63)-linked polyubiquitination, directly interact with PARPs/PARGs. Activation of pathogen-associated molecular pattern (PAMP)-triggered immunity promotes these interactions and enhances PARylation of UBC13. Both parp1 parp2 and ubc13a ubc13b mutants are compromised in immune responses with increased accumulation of total pathogenesis-related (PR) proteins but decreased accumulation of secreted PR proteins. Protein disulfide-isomerases (PDIs), essential components of endoplasmic reticulum quality control (ERQC) that ensure proper folding and maturation of proteins destined for secretion, complex with PARPs/PARGs and are PARylated upon PAMP perception. Significantly, PARylation of UBC13 regulates K63-linked ubiquitination of PDIs, which may further promote their disulfide isomerase activities for correct protein folding and subsequent secretion. Taken together, these results indicate that plant immunity is coordinately regulated by PARylation and K63-linked ubiquitination.

Two new triucallane triterpenoids, polystanin F (1) and polystanin G (2), along with eight known compounds (3-10) were isolated from the fruits of Aphanamixis polystachya. Their structures were established on the basis of extensive spectroscopic analysis. Moreover, eight compounds were evaluated for their in vitro cytotoxicity against three cancer cell lines (liver cancer RT112, colon cancer HCT-116 and breast cancer M231) using the MTT method. Compound 7 showed significant cytotoxic activity against HCT-116 with IC50 1.27 µM.

Objectives The new antituberculous drugs delamanid and bedaquiline form the last line of defence against drug-resistant tuberculosis (TB). Understanding the background prevalence of resistance to new drugs can help predict the lifetime of these drugs’ effectiveness and inform regimen design. Methods Mycobacterium tuberculosis without prior exposure to novel anti-TB drugs were analysed retrospectively. Drug susceptibility testing for bedaquiline, delamanid, linezolid, clofazimine and widely used first- and second-line anti-TB drugs was performed. All TB isolates with resistance to new or repurposed drugs were subjected to whole-genome sequencing to explore the molecular characteristics of resistance and to perform phylogenetic analysis. Results Overall, resistance to delamanid, bedaquiline, linezolid and clofazimine was observed in 0.7% (11/1603), 0.4% (6/1603), 0.4% (7/1603) and 0.4% (6/1603) of TB isolates, respectively. Moreover, 1.0% (1/102), 2.9% (3/102), 3.9% (4/102) and 1.0% (1/102) of multidrug-resistant TB (MDR-TB) were resistant to bedaquiline, delamanid, linezolid and clofazimine, respectively. Whereas 22.2% (2/9) of extensively-drug resistant tuberculosis (XDR-TB) isolates were resistant to both delamanid and linezolid, and none was resistant to bedaquiline or clofazimine. Phylogenetic analysis showed that recent transmission occurred in two XDR-TB with additional resistance to delamanid and linezolid. None known gene mutation associated with delamanid resistance was detected. All four isolates with cross-resistance to bedaquiline and clofazimine had a detected gene mutation in Rv0678. Three of five strains with linezolid resistance had a detected gene mutation in rplC. Conclusion Detection of resistance to new anti-TB drugs emphasises the pressing need for intensive surveillance for such resistance before their wide usage.

Nutrient balance is essential for attaining high yield and improving profits in agricultural farming systems, and crop nutrient uptake ratio and stoichiometry can indicate crop nutrient limitations in the field. We collected a large amount of field data to study the variations in yield, nutrient uptake and nutrient stoichiometry of peanut (Arachis hypogaea L.) in Southeast China (SEC), North-central China (NCC), and Northeast China (NEC), during 1993 to 2018. Peanut pod yield gradually increased from 1993 to 2018, with average yields of 4 148, 5 138, and 4 635 kg ha−1 in SEC, NCC, and NEC, respectively. The nitrogen (N) internal efficiency (NIE, yield to N uptake ratio) was similar among the three regions, but phosphorus (P) IE (PIE, yield to P uptake ratio) changed from low to high among regions: NCC

Background CSN5, a member of Cop9 signalosome, is essential for protein neddylation. It has been supposed to serve as an oncogene in some cancers. However, the role of CSN5 has not been investigated in cervical cancer yet. Methods Data from TCGA cohorts and GEO dataset was analyzed to examine the expression profile of CSN5 and clinical relevance in cervical cancers. The role of CSN5 on cervical cancer cell proliferation was investigated in cervical cancer cell lines, Siha and Hela, through CSN5 knockdown via CRISPR–CAS9. Western blot was used to detect the effect of CSN5 knockdown and overexpression. The biological behaviors were analyzed by CCK8, clone formation assay, 3-D spheroid generation assay and cell cycle assay. Besides, the role CSN5 knockdown in vivo was evaluated by xenograft tumor model. MLN4924 was given in Siha and Hela with CSN5 overexpression. Results We found that downregulation of CSN5 in Siha and Hela cells inhibited cell proliferation in vitro and in vivo, and the inhibitory effects were largely rescued by CSN5 overexpression. Moreover, deletion of CSN5 caused cell cycle arrest rather than inducing apoptosis. Importantly, CSN5 overexpression confers resistance to the anti-cancer effects of MLN4924 (pevonedistat) in cervical cancer cells. Conclusions Our findings demonstrated that CSN5 functions as an oncogene in cervical cancers and may serve as a potential indicator for predicting the effects of MLN4924 treatment in the future.

Background Both natural killer (NK) and CD3+CD56+natural killer T (NKT)-like cells play critical roles in the antitumor response. This study aimed to explore the effects of stereotactic body radiotherapy (SBRT) on peripheral NK and NKT-like cells in patients with hepatocellular carcinoma (HCC), and to identify possible surface markers on these cells that correlate with the prognosis. Methods Twenty-five HCC patients were prospectively enrolled in our study, and 10 healthy individuals were served as healthy controls. Flow cytometry was used to determine the counts and the percentages of peripheral NK and NKT-like cells, cells with certain receptors, and cells with intracellular interferon-γ and TNF-α secretion at different time points, including time points of prior to SBRT, at post-SBRT, and 3-month and 6-month after treatment. The Kaplan-Meier method with the log-rank test was applied for survival analysis. Results The peripheral NKT-like cells was increased at post-SBRT. Meanwhile, elevated levels of inhibitory receptors and reduced levels of activating receptors of NK cells were also observed in NK cells at post-SBRT, but the levels was not significantly different at 3-month and 6-month as compared with the baseline levels. Lower percentage of NKp30+NK cells before SBRT and higher percentage of CD158b+NK cells after SBRT were associated with poor progression-free survival. In addition, higher percentage of CD3+CD56+ NKT-like cells was associated with a higher overall survival rate in HCC patients. Conclusions SBRT has an apparent effect on both peripheral NK and CD3+CD56+NKT-like cells. Lower percentage of NKp30+NK cells before SBRT and higher percentage of CD158b+NK cells after SBRT are correlated with poor patients' PFS. Higher percentage of CD3+CD56+ NKT-like cells is associated with higher OS in HCC patients.

Background The coronavirus disease 2019 (COVID-19) has quickly spread across the world. However, the nutritional status of COVID-19 patients has not yet been extensively examined. Objectives The aim of this study was to evaluate the nutritional status of COVID-19 patients and to identify factors independently associated with malnutrition risk. Methods In this single-center, cross-sectional study, we analyzed data from 760 hospitalized COVID-19 patients between 29 January 2020 and 15 March 2020. Based on the Nutrition Risk Screening (NRS) 2002 score, we divided patients into the normal nutrition group (NRS score

The Zygosaccharomyces is notorious for its remarkable spoilage characteristics. In the present study, the visual and rapid identification of the genus Zygosaccharomyces was performed by a loop-mediated isothermal amplification (LAMP) assay using specific primers in Mini Dry Bath within 30 min at 65°C followed by a lateral flow dipstick (LFD) detection. The sensitivity evaluation revealed LAMP-LFD assay with 1.0×101 copies/μL of Zygosaccharomyces DNA as its detection limit, which was the same as the methods of real-time quantitative PCR (qPCR) and conventional polymerase chain reaction (PCR). However, qPCR or PCR methods not only need to be performed in a specialist analytical laboratory with expensive equipment but also with risk of aerosol pollution. The LAMP-LFD assay had no cross-reactivity against 10 other yeast species and its specificity was 100%. A total of 25 Qiangli loquat Dew samples (17 bottles bulged and eight normal-appearing) were detected within 40 min with 100 and 92.0% accurately and specifically, when compared with the qPCR assay and the microbiology culture method, respectively. Therefore, the simple, fast, sensitive and low-cost LAMP-LFD assay is an effective and useful tool for the on-site identification of the genus Zygosaccharomyces. Key words: Zygosaccharomyces, on-site detection, loop-mediated isothermal amplification (LAMP), lateral flow dipstick (LFD).

Yap is the key effector of Hippo signaling; however, its role in embryonic stem cells (ESCs) remains controversial. Here, we identify two Yap splicing isoforms (Yap472 and Yap488), which show equal expression levels but heterogeneous distribution in ESCs. Knockout (KO) of both isoforms reduces ESC self-renewal, accelerates pluripotency exit, but arrests terminal differentiation, while overexpression of each isoform leads to the reverse phenotype. The effect of both Yap isoforms on self-renewal is Teads-dependent and mediated by c-Myc. Nonetheless, different isoforms are found to affect overlapping yet distinct genes, and confer different developmental potential to Yap-KO cells, with Yap472 exerting a more pronounced biological effect and being more essential for neuroectoderm differentiation. Constitutive activation of Yaps, particularly Yap472, dramatically upregulates p53 and Cdx2, inducing trophectoderm trans-differentiation even under self-renewal conditions. These findings reveal the combined roles of different Yap splicing isoforms and mechanisms in regulating self-renewal efficiency and differentiation potential of ESCs.

As one of the core framework proteins of nuclear pore complex (NPC), nucleoporin Nupl70 acts as a structural adapter between the nucleolus and nuclear pore membrane and maintains the stability of NPC structure through interaction with other proteins. In this study, we identified a Nup170 protein in the microsporidian Nosema bombycis for the first time and named it as NbNup170. Secondary structure prediction showed that the NbNup170 contains α-helices and random coils. The three-dimensional structure of NbNup170 is elliptical in shape. Phylogenetic analysis based on the Nup170 and homologous sequences showed that N. bombycis clustered together with Vairimorpha ceranae and Vairimorpha apis. The immunofluorescence localization results showed that the NbNup170 was located on the plasma membrane of the dormant spore and transferred to the surface of sporoplasm in a punctate pattern when the dormant spore has finished germination, and that NbNup170 was distributed on the nuclear membrane and both sides of the nuclei of early proliferative phase, and only on the nuclear membrane during sporogonic phase in the N. bombycis. qPCR analysis showed that the relative expression level of NbNup170 maintained at a low level from 30 to 78 h post-infection with N. bombycis, then reached the highest at 102 h, while that of NbNup170 was repressed at a very low level throughout its life cycle by RNA interference. These results suggested that NbNup170 protein is involved in the proliferative phase and active during the sporogonic phase of N. bombycis.

Long non-coding RNAs (lncRNAs) are widely involved in a variety of biological processes, including epithelial-mesenchymal transition (EMT). In the current study, we found that lncRNA small nucleolar RNA host gene 8 (SNHG8) was tightly correlated with EMT-associated gene signatures, and was down-regulated by Zinc finger E-box-binding homeobox 1 (ZEB1) during EMT progress. Functionally, knockdown of SNHG8 induced EMT in epithelial cells, through destabilizing the CDH1 mRNA dependent on a 17-nucleotide sequence shared by SNHG8 and CDH1. In addition, analysis with public database showed that SNHG8 tended to be down-regulated in different cancer types and the lower expression of SNHG8 predicted poorer prognosis. Taken together, our study reports a ZEB1-repressed lncRNA SNHG8 which is important for stabilizing CDH1 mRNA, thereby maintaining the epithelial status of epithelial cells.

N6-methyladenosine (m6A) is the most abundant and prevalent epigenetic modification of mRNA in mammals. This dynamic modification is regulated by m6A methyltransferases and demethylases, which control the fate of target mRNAs through influencing splicing, translation and decay. Recent studies suggest that m6A modification plays an important role in the progress of cardiac remodeling and cardiomyocyte contractile function. However, the exact roles of m6A in cardiovascular diseases (CVDs) have not been fully explained. In this review, we summarize the current roles of the m6A methylation in the progress of CVDs, such as cardiac remodeling, heart failure, atherosclerosis (AS), and congenital heart disease. Furthermore, we seek to explore the potential risk mechanisms of m6A in CVDs, including obesity, inflammation, adipogenesis, insulin resistance (IR), hypertension, and type 2 diabetes mellitus (T2DM), which may provide novel therapeutic targets for the treatment of CVDs.

Fusarium wilt caused by the ascomycete fungus Fusarium oxysporum is a devastating disease of many economically important crops. The mechanisms underlying plant responses to F. oxysporum infections remain largely unknown. We demonstrate here that a water-soluble, heat-resistant and nonproteinaceous F. oxysporum cell wall extract (FoCWE) component from multiple F. oxysporum isolates functions as a race-nonspecific elicitor, also termed pathogen-associated molecular pattern (PAMP). FoCWE triggers several demonstrated immune responses, including mitogen-activated protein (MAP) kinase phosphorylation, reactive oxygen species (ROS) burst, ethylene production, and stomatal closure, in cotton and Arabidopsis. Pretreated FoCWE protects cotton seeds against infections by virulent F. oxysporum f. sp. vasinfectum (Fov), and Arabidopsis plants against the virulent bacterium, Pseudomonas syringae, suggesting the potential application of FoCWEs in crop protection. Host-mediated responses to FoCWE do not appear to require LYKs/CERK1, BAK1 or SOBIR1, which are commonly involved in PAMP perception and/or signalling. However, FoCWE responses and Fusarium resistance in cotton partially require two receptor-like proteins, GhRLP20 and GhRLP31. Transcriptome analysis suggests that FoCWE preferentially activates cell wall-mediated defence, and Fov has evolved virulence mechanisms to suppress FoCWE-induced defence. These findings suggest that FoCWE is a classical PAMP that is potentially recognised by a novel pattern-recognition receptor to regulate cotton resistance to Fusarium infections.

As sessile organisms, plants are exposed to pathogen invasions and environmental fluctuations. To overcome the challenges of their surroundings, plants acquire the potential to sense endogenous and exogenous cues, resulting in their adaptability. Hence, plants have evolved a large collection of plasma membrane-resident receptors including, RECEPTOR-LIKE KINASEs (RLKs) and RECEPTOR-LIKE PROTEINs (RLPs) to perceive those signals and regulate plant growth, development, and immunity. The ability of RLKs and RLPs to recognize distinct ligands relies on diverse categories of extracellular domains evolved. Co-regulatory receptors are often required to associate with RLKs and RLPs to facilitate cellular signal transduction. RECEPTOR-LIKE CYTOPLASMIC KINASEs (RLCKs) also associate with the complex, bifurcating the signal to key signaling hubs, such as MITOGEN-ACTIVATED PROTEIN KINASE (MAPK) cascades, to regulate diverse biological processes. Here, we discuss recent knowledge advance in understanding the roles of RLKs and RLPs in plant growth, development, and immunity, and their connection with co-regulatory receptors, leading to activation of diverse intracellular signaling pathways. This article is protected by copyright. All rights reserved.

Leptospirosis, caused by pathogenic Leptospira species, has emerged as a widespread zoonotic disease worldwide. Macrophages mediate the elimination of pathogens through phagocytosis and cytokine production. Scavenger receptor A1 (SR-A1), one of the critical receptors mediating this process, plays a complicated role in innate immunity. However, the role of SR-A1 in the immune response against pathogenic Leptospira invasion is unknown. In the present study, we found that SR-A1 is an important nonopsonic phagocytic receptor on murine macrophages for Leptospira. However, intraperitoneal injection of leptospires into WT mice presented with more apparent jaundice, subcutaneous hemorrhaging, and higher bacteria burdens in blood and tissues than that of SR-A1-/- mice. Exacerbated cytokine and inflammatory mediator levels were also observed in WT mice and higher recruited macrophages in the liver than those of SR-A1-/- mice. Our findings collectively reveal that although beneficial in the uptake of Leptospira by macrophage, SR-A1 might be exploited by Leptospira to modulate inflammatory activation and increase the susceptibility of infection in the host. These results provide our new insights into the innate immune response during early infection by L. interrogans.

Duck egg white (DEW) is considered as an abandoned protein resource. For a higher-value utilization, preparation of immunomodulatory peptides from the extracted ovalbumin in DEW was explored. Among the hydrolysates catalyzed by five proteases, papain hydrolysate (PH) shows the highest degree of hydrolysis and the strongest immunomodulatory activity. PH could significantly enhance the phagocytic capacity and promote the NO, TNF-α, and IL-6 secretion of RAW 264.7 cells, involving toll-like receptor 2 and 4. After purification, nine identified peptides were synthesized to confirm the immunomodulatory effect, and five of them exhibit a strong activity. The peptide, TQIDKVVHFDKLPGF, presents the highest immunomodulatory activity. Moreover, the results of molecular docking indicate that nine peptides interacted with toll-like receptor 2 and 4 and all show good affinity. Furthermore, three peptides with high affinity and strong immune activity were selected for interaction site map analysis. Three peptides could form hydrogen bonds with the receptor and bind stably, which contributes to the immunomodulatory activity of the peptide. Results suggest that DEW can be a promising source of immunomodulatory peptides.

Monoclonal antibodies (mAbs) encoded by IGHV3-53 (VH3-53) targeting the spike receptor-binding domain (RBD) have been isolated from different COVID-19 patients. However, the existence and prevalence of shared VH3-53-encoded antibodies in the antibody repertoires is not clear. Using antibody repertoire sequencing, we found that the usage of VH3-53 increased after SARS-CoV-2 infection. A highly shared VH3-53-J6 clonotype was identified in 9 out of 13 COVID-19 patients. This clonotype was derived from convergent gene rearrangements with few somatic hypermutations and was evolutionary conserved. We synthesized 34 repertoire-deduced novel VH3-53-J6 heavy chains and paired with a common IGKV1-9 light chain to produce recombinant mAbs. Most of these recombinant mAbs (23/34) possess RBD binding and virus-neutralizing activities, and recognize ACE2 binding site via the same molecular interface. Our computational analysis, validated by laboratory experiments, revealed that VH3-53 antibodies targeting RBD are commonly present in COVID-19 patients’ antibody repertoires, indicating many people have germline-like precursor sequences to rapidly generate SARS-CoV-2 neutralizing antibodies. Moreover, antigen-specific mAbs can be digitally obtained through antibody repertoire sequencing and computational analysis.

Nuclear receptor Nur77 participates in multiple metabolic regulations and plays paradoxical roles in tumorigeneses. Herein, we demonstrated that the knockout of Nur77 stimulated mammary tumor development in two mouse models, which would be reversed by a specific reexpression of Nur77 in mammary tissues. Mechanistically, Nur77 interacted and recruited corepressors, the SWI/SNF complex, to the promoters of CD36 and FABP4 to suppress their transcriptions, which hampered the fatty acid uptake, leading to the inhibition of cell proliferation. Peroxisome proliferator-activated receptor-γ (PPARγ) played an antagonistic role in this process through binding to Nur77 to facilitate ubiquitin ligase Trim13-mediated ubiquitination and degradation of Nur77. Cocrystallographic and functional analysis revealed that Csn-B, a Nur77-targeting compound, promoted the formation of Nur77 homodimer to prevent PPARγ binding by steric hindrance, thereby strengthening the Nur77’s inhibitory role in breast cancer. Therefore, our study reveals a regulatory function of Nur77 in breast cancer via impeding fatty acid uptake.

The human body is one of the most sophisticated material systems. It is still a considerable challenge to biomimic the “life-design” process to construct a part of “life” in vivo. Herein, we mimick...

Summary Salt stress dramatically impedes plant growth and development as well as crop yield. The apple production regions are reduced every year, because of the secondary salt damage by improper fertilization and irrigation. To expand the cultivation area of apple (Malus domestica) and select salt‐resistant varieties, the mechanism of salt tolerance in apple is necessary to be clarified. The miR156/SPL regulatory module plays key roles in embryogenesis, morphogenesis, life cycle stage transformation, flower formation and other processes. However, its roles in the mechanisms of salt tolerance are unknown. In order to elucidate the mechanism of 156/SPL regulating salt stress in apple, we performed RLM‐5’ RACE and stable genetic transformation technology to verify that both mdm‐MIR156a and MdSPL13 responded to salt stress in apple and that the latter was the target of the former. MIR156a overexpression weakened salt resistance in apple whereas MdSPL13 overexpression strengthened it. A total of 6094 differentially expressed genes relative to nontransgenic apple plants were found by RNA‐Seq analysis of MdSPL13OE. Further verification indicated that MdSPL13 targeted the MdWRKY100 gene promoter. Moreover, MdWRKY100 overexpression enhanced salt tolerance in apple. Our results revealed that the miR156/SPL module regulates salt tolerance by up‐regulating MdWRKY100 in apple. This study is the first to elucidate the mechanism underlying the miRNA network response to salt stress in apple and provides theoretical and empirical bases and genetic resources for the molecular breeding of salt tolerance in apple.

Although bacterial small noncoding RNAs (sRNAs) are known to play a critical role in various cellular processes, including pathogenesis, the identity and action of such sRNAs are still poorly understood in many organisms. Here we have performed a genome‐wide screen and functional analysis of the sRNAs in Xanthomonas campestris pv. campestris (Xcc), an important phytopathogen. The 50–500‐nt RNA fragments isolated from the wild‐type strain grown in a virulence gene‐inducing condition were sequenced and a total of 612 sRNA candidates (SRCs) were identified. The majority (82%) of the SRCs were derived from mRNA, rather than specific sRNA genes. A representative panel of 121 SRCs were analysed by northern blotting; 117 SRCs were detected, supporting the contention that the overwhelming majority of the 612 SRCs identified are indeed sRNAs. Phenotypic analysis of strains overexpressing different candidates showed that a particular sRNA, RsmU, acts as a negative regulator of virulence, the hypersensitive response, and cell motility in Xcc. In vitro electrophoretic mobility shift assay and in vivo coimmunoprecipitation analyses indicated that RsmU interacted with the global posttranscriptional regulator RsmA, although sequence analysis displayed that RsmU is not a member of the sRNAs families known to antagonize RsmA. Northern blotting analyses demonstrated that RsmU has two isoforms that are processed from the 3′‐untranslated region of the mRNA of XC1332 predicted to encode ComEA, a periplasmic protein required for DNA uptake in bacteria. This work uncovers an unexpected major sRNA biogenesis strategy in bacteria and a hidden layer of sRNA‐mediated virulence regulation in Xcc., The RsmA‐sequestering noncoding RNA RsmU derived from the 3′‐UTR of XC1332 mRNA negatively regulates virulence, the hypersensitive response, and cell motility in Xanthomonas campestris.

MdHAL3 has PPCDC activity and is involved in the salt tolerance of autotetraploid apple. Apple (Malus × domestica) is the most widely planted fruit tree species worldwide. However, the growth and development of apple have been increasingly affected by abiotic stress, such as high salinity. In our previous study, RNA sequencing (RNA-seq) analysis revealed that the expression level of the MdHAL3 gene was significantly upregulated in the autotetraploid apple cultivar Hanfu. In the present study, we first isolated HAL3, whose product was shown to exert 4′-phosphopantothenoylcysteine decarboxylase (PPCDC) activity, from apple. MdHAL3 was expressed in all organs of apple, and its expression was rapidly induced by salt stress. The MdHAL3 protein was localized to the cytomembrane and cytoplasm. Five MdHAL3 overexpression (OE) lines and five MdHAL3-RNAi apple lines were obtained. We found that MdHAL3 enhanced the salt stress tolerance of apple and that the OE plants rooted more easily than the wild-type (WT) plants. The coenzyme A (CoA) content in the leaves of the OE plants was greater than that in the leaves of the WT plants, and the CoA content in the MdHAL3-RNAi plants was lower than that in the WT plants. Taken together, our findings indicate that MdHAL3 plays an essential role in the response to salt stress in apple.

Background Tomatoes (Lycopersicon esculentum Mill) are key foods, and their molecular biology and evolution have been well described. Tomato plants originated in the tropics and, thus, are cold sensitive. Results Here, we generated LeGPA1 overexpressing and RNA-interference (RNAi) transgenic tomato plants, which we then used to investigate the function of LeGPA1 in response to cold stress. Functional LeGPA1 was detected at the plasma membrane, and endogenous LeGPA1 was highly expressed in the roots and leaves. Cold treatment positively induced the expression of LeGPA1. Overexpression of LeGPA1 conferred tolerance to cold conditions and regulated the expression of genes related to the INDUCER OF CBF EXPRESSION-C-REPEAT-BINDING FACTOR (ICE-CBF) pathway in tomato plants. In the LeGPA1-overexpressing transgenic plants, the superoxide dismutase, peroxidase, and catalase activities and soluble sugar and proline contents were increased, and the production of reactive oxygen species and membrane lipid peroxidation decreased under cold stress. Conclusions Our findings suggest that improvements in antioxidant systems can help plants cope with the oxidative damage caused by cold stress, thereby stabilizing cell membrane structures and increasing the rate of photosynthesis. The data presented here provide evidence for the key role of LeGPA1 in mediating cold signal transduction in plant cells. These findings extend our knowledge of the roles of G-proteins in plants and help to clarify the mechanisms through which growth and development are regulated in processing tomato plants.

Rhaponticin is a stilbenoid glucoside compound, found in medicinal plant of rhubarb rhizomes. Rhapontigenin (RHAG), the stilbene aglycone metabolite of rhaponticin, has shown various biological activities including anticancer activities to act a potential human cytochrome P450 inhibitor, antihyperlipidemic effect, anti-allergic action, antioxidant and antibacterial activities. Moreover, it was reported to scavenge intracellular Reactive Oxygen Species (ROS), the 1,1-Diphenyl-2-Picrylliydrazyl (DPPH) radical, and Hydrogen Peroxide (H2O2). Meanwhile, RHAG exhibited the inhibitory activity for the synthesis of DNA, RNA and protein, and also presented the capacity of inducing morphological changes and apoptosis of C. albicans. Here, the structure, pharmacokinetics, pharmacological effects as well as underlying mechanisms of rhaponticin and its metabolite, RHAG, have been extensively reviewed. This review will provide a certain reference value for developing the therapeutic drug of rhaponticin or RHAG.

Interleukin (IL)-37 has anti-tumor effects in hepatocellular carcinoma (HCC). Evidence shows that tumor-associated macrophages (TAMs) promote tumor progression. This study was designed to investigate the functional role of IL-37-mediated polarization of TAMs in HCC progression. HCC patient-derived TAMs were transfected with lentiviruses expressing IL-37 (LV-IL-37) and IL-37 siRNA and then the conditioned medium from TAMs were used to culture HCC cells (HepG2 and Huh-7). The phenotype of the macrophages was evaluated by detecting M1- or M2- type specific markers and cytokines. Cell proliferation, migration, and invasion were assessed. A tumor xenograft mouse model was generated with a subcutaneous injection of a mixture of HepG2 cells and TAMs/LV-IL-37. HCC patient-derived PBMCs showed M2 polarization and decreased IL-37 expression. Furthermore, IL-37 promoted TAMs polarization from M2 to M1 subtype through inhibiting the IL-6/STAT3 signaling. Moreover, IL-6 upregulation by recombinant human IL-6 (rhIL-6) blocked the IL-37 overexpression-mediated inhibition of HCC cell proliferation, migration, and invasion. In addition, IL-37 overexpression in HCC patient-derived TAMs inhibited tumor growth in vivo. Collectively, IL-37 suppresses HCC growth through inhibiting M2 polarization of TAMs via regulating the IL-6/STAT3 pathway.

Cancer therapeutic strategies based on angiogenesis attract great attention from fundamental and clinical research. Blocking oxygen and nutrition supply to tumor cells could inhibit the growth of tumors based on occlusion of blood vessels in the tumor. Herein, we report a dual-responsive peptide-based nanoparticle, mimicking the laminin fibrillogenesis specifically and highly efficiently in tumor vessels, resulting in the blockage of tumor vessels and the growth inhibition of tumors. The laminin mimic peptide (LMMP) is designed with a fibrillation sequence, a pH-responsive sequence, and a targeting sequence. The LMMP in nanoformulations is delivered to blood vessels in the tumors, where the microenvironment (pH and microthrombus) enable LMMP to process laminin fibrillogenesis, constructing fibrous networks. The laminin-like fibrous networks capture red blood cells etc., forming occlusion specifically in the tumor blood vessels to inhibit the growth of the tumor.

Despite the vast carbon (C) stock of crop root residues in arable ecosystems, the microbial assimilation mechanism of crop root derived‐C is poorly understood. In this study, a DNA‐based stable isotope probing (DNA‐SIP) approach was used to explore and characterize the diversity of the soil bacterial community assimilating C derived from ¹³C‐labelled rice root residues during a 90‐day incubation. Overall, ¹³C‐assimilating bacterial groups with various characteristics were identified with the occurrence of strong priming effects on soil native C. Significant increases of Actinobacteria, Proteobacteria and Bacteroidetes abundances within the ¹³C‐assimilating bacterial community were observed. Generally, Streptomyces were the predominant utilizers of ¹³C derived from rice root residues within a 28‐day incubation. The ¹³C‐labelling of Pseudomonas, which was continuously detected during incubation, indicated stronger effects at the later decomposition stage. The role of genera Kitasatospora, Catenulispora, Nocardioides, Flavisolibacter and Niastella in ¹³C‐labelled rice root residues assimilation was also observed. Meanwhile, incorporation of rice root residues stimulated the growth of certain bacterial groups that incorporated unlabelled native soil C, including Chloroflexi, Acidobacteria, Planctomycetes, Verrumicrobia and Nitrospirae. HIGHLIGHTS: The microbial mechanism of the utilization of crop root residues is largely neglected. We explored the diversity of bacterial communities assimilating rice root residues with DNA‐SIP Actinobacteria, Proteobacteria and Bacteroidetes were dominant decomposers of root residues Streptomyces and Pseudomonas were consistently detected as key assimilators during decomposition

Undifferentiation is a key feature of nasopharyngeal carcinoma (NPC), which presents as a unique opportunity for intervention by differentiation therapy. In this study, we found that SOX1 inhibited proliferation, promoted differentiation, and induced senescence of NPC cells, which depended on its transcriptional function. RNA-Seq-profiling analysis showed that multiple undifferentiated markers of keratin family, including KRT5, KRT13, and KRT19, were reduced in SOX1 overexpressed NPC cells. Interestingly, gene ontology (GO) analysis revealed genes in SOX1 overexpressed cells were enriched in extracellular functions. The data of LC/MS untargeted metabolomics showed that the content of retinoids in SOX1 overexpressed cells and culture medium was both higher than that in the control group. Subsequently, we screened mRNA level of genes in retinoic acid (RA) signaling or metabolic pathway and found that the expression of UDP-glucuronosyltransferases was significantly decreased. Furtherly, UGT2B7 could rescue the differentiation induced by SOX1 overexpression. Inhibition of UGTs by demethylzeylasteral (T-96) could mimic SOX1 to promote the differentiation of NPC cells. Thus, we described a mechanism by which SOX1 regulated the differentiation of NPC cells by activating retinoid metabolic pathway, providing a potential target for differentiation therapy of NPC.

The detection of microorganism-associated ligands by plant cells activates a signalling cascade in which the kinase BIK1 is monoubiquinated, released from the FLS2-BAK1 complex, and internalized by endocytosis. Recognition of microbe-associated molecular patterns (MAMPs) by pattern recognition receptors (PRRs) triggers the first line of inducible defence against invading pathogens(1-3). Receptor-like cytoplasmic kinases (RLCKs) are convergent regulators that associate with multiple PRRs in plants(4). The mechanisms that underlie the activation of RLCKs are unclear. Here we show that when MAMPs are detected, the RLCK BOTRYTIS-INDUCED KINASE 1 (BIK1) is monoubiquitinated following phosphorylation, then released from the flagellin receptor FLAGELLIN SENSING 2 (FLS2)-BRASSINOSTEROID INSENSITIVE 1-ASSOCIATED KINASE 1 (BAK1) complex, and internalized dynamically into endocytic compartments. The Arabidopsis E3 ubiquitin ligases RING-H2 FINGER A3A (RHA3A) and RHA3B mediate the monoubiquitination of BIK1, which is essential for the subsequent release of BIK1 from the FLS2-BAK1 complex and activation of immune signalling. Ligand-induced monoubiquitination and endosomal puncta of BIK1 exhibit spatial and temporal dynamics that are distinct from those of the PRR FLS2. Our study reveals the intertwined regulation of PRR-RLCK complex activation by protein phosphorylation and ubiquitination, and shows that ligand-induced monoubiquitination contributes to the release of BIK1 family RLCKs from the PRR complex and activation of PRR signalling.

Glutamate receptor-like (GLR) proteins are ligand-gated ion channels regulating various plant physiology. They function as calcium channels in plant immunity and mediate long-distance defense to herbivores. A recent study by Liu et al. identified a cotton GLR as a noncanonical resistance protein to Fusarium wilt, expanding the paradigm of GLR functions in plant immunity.

Kruppel-like factors (KLFs) belong to a family of transcription factors that play fundamentally important role in various biological processes. The discovery of the Yamanaka factors in reprogramming of somatic cells into pluripotent stem cells has demonstrated that KLFs are required in various phases of reprogramming. Among these, KLF4, KLF2, or KLF5 can be exogenously expressed together with OCT4, SOX2, and MYC to generate induced pluripotent stem cells (iPSCs). With improved understanding of the mechanisms by which transcription factors govern cell identity, we now know that pluripotency is regulated by an autoregulated transcriptional feedback network. KLF4 is one of the key pluripotency factors that activates other pluripotency factors while its own expression is regulated by the same factors it activates. KLF4 plays a dual role in reprograming. It acts as a repressor of somatic-specific genes and as a pioneer factor to activate epigenetically suppressed pluripotency genes during early reprogramming. It also acts as an activator of pluripotency genes by binding to super-enhancers of pluripotency factors to facilitate long-range interactions among pluripotency factor binding sites. KLFs are also markers of naive pluripotency. KLF17 is the newest KLF that has been identified to be a marker for naive PSCs and has the ability to reprogram primed PSC to naive PSC. The understanding of how protein structures of KLFs relate to their function in cellular reprogramming is incomplete. Knowledge of their structure and function relationship in reprogramming should significantly contribute to the clinical applications of iPSC technology.

Nutrient requirements for single-season rice using the quantitative evaluation of the fertility of tropical soils (QUEFTS) model in China have been estimated in a previous study, which involved all the rice varieties, however, it is unclear whether a similar result can be obtained for different rice varieties. In this study, data were collected from field experiments conducted from 2016 to 2019 in Zhejiang Province, China. The dataset was separated into two parts: japonica/indica hybrid rice and japonica rice. To produce 1000 kg of grain, 13.5 kg N, 3.6 kg P, and 20.4 kg K were required in the above-ground plant dry matter for japonica/indica hybrid rice, and the corresponding internal efficiencies (IEs) were 74.0 kg grain per kg N, 279.1 kg grain per kg P, and 49.1 kg grain per kg K. For japonica rice, 17.6 kg N, 4.1 kg P, and 23.0 kg K were required to produce 1000 kg of grain, and the corresponding IEs were 56.8 kg grain per kg N, 244.6 kg grain per kg P, and 43.5 kg grain per kg K. Field validation experiments indicated that the QUEFTS model could be used to estimate nutrient uptake of different rice varieties. We suggest that variety should be taken into consideration when estimating nutrient uptake for rice using the QUEFTS model, which would improve this model.

The spatial distribution between dark matter and baryonic matter of the Universe is biased or deviates from each other. In this work, by comparing the results derived from IllustrisTNG and WIGEON simulations, we find that many results obtained from TNG are similar to those from WIGEON data, but differences between the two simulations do exist. For the ratio of density power spectrum between dark matter and baryonic matter, as scales become smaller and smaller, the power spectra for baryons are increasingly suppressed for WIGEON simulations; while for TNG simulations, the suppression stops at $k=15-20\, {h {\rm Mpc}^{-1}}$, and the power spectrum ratios increase when $k\gt 20\, {h {\rm Mpc}^{-1}}$. The suppression of power ratio for WIGEON is also redshift-dependent. From z = 1 to z = 0, the power ratio decreases from about 70 per cent to less than 50 per cent at $k=8\, {h {\rm Mpc}^{-1}}$. For TNG simulation, the suppression of power ratio is enhanced with decreasing redshifts in the scale range $k\gt 4\, {h {\rm Mpc}^{-1}}$, but is nearly unchanged with redshifts in $k\lt 4\, {h {\rm Mpc}^{-1}}$. These results indicate that turbulent heating can also have the consequence to suppress the power ratio between baryons and dark matter. Regarding the power suppression for TNG simulations as the norm, the power suppression by turbulence for WIGEON simulations is roughly estimated to be 45 per cent at $k=2\, {h {\rm Mpc}^{-1}}$, and gradually increases to 69 per cent at $k=8\, {h {\rm Mpc}^{-1}}$, indicating the impact of turbulence on the cosmic baryons are more significant on small scales.

In many instances Fusarium oxysporum genomes are complex and challenging to assemble mainly due to the increased number of repetitive elements and variable numbers of supernumerary chromosomes, which are primarily associated with pathogenicity. Hence, to obtain the accurate F. oxysporum genome assembly and high-resolution sequence information, protocols for versatile, reliable, and high recovery of high-quality DNA for diverse sequencing platforms are instrumental. Here, we describe two protocols for the isolation of DNA from isolates of F. oxysporum. One is a quick and easy method for high-throughput extraction of DNA to rapidly screen diverse isolates by marker-assisted PCR analysis. Another is to harvest high-quality and high-molecular-weight DNA for whole-genome sequencing. In addition, we also include a library preparation protocol optimized for the third-generation sequencing technology using the portable MinION device to obtain long-read sequences. These protocols can be potentially further applied for all Fusarium spp. and other fungal pathogens, including Verticillium.

As a frequently occurring infectious disease mainly caused by Candida albicans, vulvovaginal candidosis (VVC) affects more than 100 million women worldwide every year. Multiple factors that influence C. albicans colonisation have been linked to the incidence of VVC, including high levels of circulating oestrogen due to pregnancy, the use of oral contraceptives, and hormone replacement therapy. This review provides an overview of the current understanding of the mechanism(s) by which oestrogen contributes to VVC, which might provide meaningful guidance to the prevention and treatment of this disease.

Bacillus spp. is effective biocontrol agents for Fusarium wilt of banana (FWB), tropical race 4 (TR4). This study explores the colonization by Bacillus subtilis, Bacillus velezensis, and Bacillus amyloliquefaciens of host banana plants and elucidates the mechanism of antagonistic TR4 biocontrol. The authors selected one B. subtilis strain, three B. velezensis strains, and three B. amyloliquefaciens strains that are proven to significantly inhibit TR4 in vitro, optimized the genetic transformation conditions and explored their colonization process in banana plants. The results showed that we successfully constructed an optimized fluorescent electro-transformation system (OD600 of bacteria concentration=0.7, plasmid concentration=50ng/μl, plasmid volume=2μl, transformation voltage=1.8kV, and transformation capacitance=400Ω) of TR4-inhibitory Bacillus spp. strains. The red fluorescent protein (RFP)-labeled strains were shown to have high stability with a plasmid-retention frequency above 98%, where bacterial growth rates and TR4 inhibition are unaffected by fluorescent plasmid insertion. In vivo colonizing observation by Laser Scanning Confocal Microscopy (LSCM) and Scanning Electron Microscopy (SEM) showed that Bacillus spp. can colonize the internal cells of banana plantlets roots. Further, fluorescent observation by LSCM showed these RFP-labeled bacteria exhibit chemotaxis (chemotaxis ratio was 1.85±0.04) toward green fluorescent protein (GFP)-labeled TR4 hyphae in banana plants. We conclude that B. subtilis, B. velezensis, and B. amyloliquefaciens can successfully colonize banana plants and interact with TR4. Monitoring its dynamic interaction with TR4 and its biocontrol mechanism is under further study.

African swine fever (ASF) is a highly contagious viral disease of domestic pigs and wild boars. For disease surveillance and control, we developed a rapid and easy luciferase immunoprecipitation assay (MB-LIPS) to detect ASF virus (ASFV) antibody. The MB-LIPS is based on magnetic beads modified with protein A/G and the recombinant fusion protein of ASFV p30 and luciferase, where p30 functioned as the recognition element and luciferase as the signal component. Incubation and washing could be finished automatically on a machine with magnetic rods. Under optimal conditions, the MB-LIPS showed 96.3% agreement to a commercial enzyme-linked immunosorbent assay (ELISA) kit for detecting ASFV antibody in swine sera. Analyzing serial dilutions of a swine serum sample showed that the MP-LIPS assay was 4 times more sensitive than the ELISA kit. The whole run of the MB-LIPS could be completed within 30 min. With its high sensitivity and simple operation, the MB-LIPS platform has great potential to be used for the detection of ASFV antibody and ASF control in small labs and farms.

Sessile plants encode a large number of small peptides and cell surface-resident receptor kinases, most of which have unknown functions. Here, we report that the Arabidopsis receptor kinase MALE DISCOVERER 1-INTERACTING RECEPTOR-LIKE KINASE 2 (MIK2) recognizes the conserved signature motif of SERINE-RICH ENDOGENOUS PEPTIDEs (SCOOPs) from Brassicaceae plants as well as proteins present in fungal Fusarium spp. and bacterial Comamonadaceae, and elicits various immune responses. SCOOP signature peptides trigger immune responses and altered root development in a MIK2-dependent manner with a sub-nanomolar sensitivity. SCOOP12 directly binds to the extracellular leucine-rich repeat domain of MIK2 in vivo and in vitro, indicating that MIK2 is the receptor of SCOOP peptides. Perception of SCOOP peptides induces the association of MIK2 and the coreceptors SOMATIC EMBRYOGENESIS RECEPTOR KINASE 3 (SERK3) and SERK4 and relays the signaling through the cytosolic receptor-like kinases BOTRYTIS-INDUCED KINASE 1 (BIK1) and AVRPPHB SUSCEPTIBLE1 (PBS1)-LIKE 1 (PBL1). Our study identifies a plant receptor that bears a dual role in sensing the conserved peptide motif from phytocytokines and microbial proteins via a convergent signaling relay to ensure a robust immune response., Peptide signals generated during plant microbe interactions can trigger immune responses in plants. Here the authors show that SCOOP12, a member of a family of peptides present in Brassicaceae plants, and SCOOP12-like motifs in Fusarium fungi, can trigger immune responses following perception by the MIK2 receptor kinase.

Decidual macrophages (dMϕ) are the second largest population of leukocytes at the maternal–fetal interface and play critical roles in maintaining pregnancy. Our previous studies demonstrated the active involvement of monoclonal nonspecific suppressor factor-β (MNSFβ) in embryonic implantation and pregnancy success. MNSFβ is a ubiquitously expressed ubiquitin-like protein that also exhibits immune regulatory potential, but its function in human dMϕ remains unknown. Here, we observed that the proportion of CD11chigh(CD11cHI) dMϕ was significantly increased in dMϕ derived from patients with recurrent pregnancy loss (RPL dMϕ) compared to those derived from normal pregnant women (Control dMϕ). The production of MNSFβ and TNFα by RPL dMϕ was also significantly increased compared to that by Control dMϕ. Conditioned medium from RPL dMϕ exerted an inhibitory effect on the invasiveness of human trophoblastic HTR8/SVneo cells, and this effect could be partially reversed by a neutralizing antibody against TNFα. Bioinformatics analysis indicated a potential interaction between MNSFβ and RC3H1, a suppressor of TNFα transcription. Immunoprecipitation experiments with human Mϕ differentiated from the human monocyte cell line Thp1 (Thp1-derived Mϕ) proved the binding of MNSFβ to RC3H1. Specific knockdown of MNSFβ in Thp1-derived Mϕ led to a marked decrease in TNFα production, which could be reversed by inhibiting RC3H1 expression. Interestingly, a significant decrease in the protein level of RC3H1 was observed in RPL dMϕ. Together, our findings indicate that aberrantly increased MNSFβ expression in dMϕ may promote TNFα productionviaits interaction with RC3H1, and these phenomena could result in the disruption of the immune balance at the maternal–fetal interface and thus pregnancy loss.

Fusarium wilt of banana (FWB) is the main threatening factor for banana production worldwide. To explore bacterial biocontrol resources for FWB, the antagonistic effective strains were isolated from banana-producing areas in Yunnan Province, China. Two isolates (YN0904 and YN1419) displaying strong antagonism against Tropical Race 4 (TR4) were identified from a total of 813 strains of endophytic bacteria. TR4 inhibition rates of YN0904 and YN1419 were 79.6% and 81.3%, respectively. By looking at morphological, molecular, physiological and biochemical characteristics, YN0904 was identified as Bacillus amyloliquefaciens, while YN1419 was identified as B. subtillis. The control effects of YN0904 and YN1419 on TR4 in greenhouse experiments were 82.6% and 85.6%, respectively. Furthermore, YN0904 obviously promoted the growth of banana plantlets. In addition, biocontrol marker genes related to the biosynthesis of antibiotics synthesized and auxin key synthetase genes could be detected in YN0904. Surprisingly, the marker gene sboA could be exclusively detected in YN1419, while other marker genes were all absent. Molecular characterization results could provide a theoretical basis for expounding the biocontrol mechanisms of these two strains. We concluded that natively antagonistic strains derived from local banana plantations could provide new biological control resources for FWB.

Tuberculosis (TB) caused by Mycobacterium tuberculosis (MTB) is a deadly infection, and increasing resistance worsens an already bad scenario. In this work, a new nanomedicine antibacterial agent, based on dihydroartemisinin (DHA) and chitosan (CS), has been successfully developed to overcome MTB’s drug-resistant. To enhance DHA’s solubility, we have prepared nanoparticles of DHA loaded CS by an ionic crosslinking method with sodium tripolyphosphate (STPP) as the crosslinking agent. The DHA-CS nanoparticles (DHA-CS NPs) have been fully characterized by scanning electron microscopy, Fourier transforms infrared spectroscopy, dynamic light scattering, and ultraviolet spectrophotometry. DHA-CS NPs show an excellent antibacterial effect on the rifampicin (RFP)-resistant strain (ATCC 35838) and, at a concentration of 8.0 μg/ml, the antibacterial impact reaches up to 61.0 ± 2.13% (n = 3). The results of Gram staining, acid-fast staining, auramine “O” staining and electron microscopy show that the cell wall of RFP-resistant strains is destroyed by DHA-CS NPs (n = 3), and it is further verified by gas chromatography-mass spectrometry. Since all the metabolites identified in DHA-CS NPs treated RFP-resistant strains indicate an increase in fatty acid synthesis and cell wall repair, it can be concluded that DHA-CS NPs act by disrupting the cell wall. In addition, the resistance of 12 strains is effectively reduced by 8.0 μg/ml DHA-CS NPs combined with RFP, with an effective rate of 66.0%. The obtained results indicate that DHA-CS NPs combined with RFP may have potential use for TB treatment.

The genetic events occurring in recurrent nasopharyngeal carcinoma (rNPC) are poorly understood. Here, we performed whole-genome and whole-exome sequencing in 55 patients with rNPC and 44 primarily diagnosed NPC (pNPC), with 7 patients having paired rNPC and pNPC samples. Previously published pNPC exome data were integrated for analysis. rNPC and pNPC tissues had similar mutational burdens, however, the number of clonal mutations was increased in rNPC samples. TP53 and three NF-κB pathway components (TRAF3, CYLD, and NFKBIA) were significantly mutated in both pNPC and rNPC. Notably, mutations in TRAF3, CYLD, and NFKBIA were all clonal in rNPC, however, 55.6% to 57.9% of them were clonal in pNPC. In general, the number of clonal mutations in NF-κB pathway–associated genes was significantly higher in rNPC than in pNPC. The NF-κB mutational clonality was selected and/or enriched during NPC recurrence. The amount of NF-κB translocated to the nucleus in samples with clonal NF-κB mutants was significantly higher than that in samples with subclonal NF-κB mutants. Moreover, the nuclear abundance of NF-κB protein was significantly greater in pNPC samples with locoregional relapse than in those without relapse. Furthermore, high nuclear NF-κB levels were an independent negative prognostic marker for locoregional relapse-free survival in pNPC. Finally, inhibition of NF-κB enhanced both radiosensitivity and chemosensitivity in vitro and in vivo. In conclusion, NF-κB pathway activation by clonal mutations plays an important role in promoting the recurrence of NPC. Moreover, nuclear accumulation of NF-κB is a prominent biomarker for predicting locoregional relapse-free survival. Significance: This study uncovers genetic events that promote the progression and recurrence of nasopharyngeal carcinoma and has potential prognostic and therapeutic implications. See related commentary by Sehgal and Barbie, p. 5915

Background Abdominal aortic aneurysm (AAA) is a focal aortic dilatation progressing towards rupture. Non-invasive AAA-associated cell proliferation biomarkers are not yet established. We investigated the feasibility of the cell proliferation radiotracer, fluorine-18-fluorothymidine ([18F]FLT) with positron emission tomography/computed tomography (PET/CT) in a progressive pre-clinical AAA model (angiotensin II, AngII infusion). Methods and Results Fourteen-week-old apolipoprotein E-knockout (ApoE−/−) mice received saline or AngII via osmotic mini-pumps for 14 (n = 7 and 5, respectively) or 28 (n = 3 and 4, respectively) days and underwent 90-minute dynamic [18F]FLT PET/CT. Organs were harvested from independent cohorts for gamma counting, ultrasound scanning, and western blotting. [18F]FLT uptake was significantly greater in 14- (n = 5) and 28-day (n = 3) AAA than in saline control aortae (n = 5) (P 18F]FLT uptake in 14-day AAA (n = 9) compared to saline-infused aortae (n = 4) (P r = 0.71, P n = 3 each) (all P Conclusions [18F]FLT uptake is increased during the active growth phase of the AAA model compared to saline control mice and late-stage AAA.

Plants deploy various immune receptors to recognize pathogens and defend themselves. Crosstalk may happen among receptor-mediated signal transduction pathways in the same host during simultaneous infection of different pathogens. However, the related function of the receptor-like kinases (RLKs) in thwarting different pathogens remains elusive. Here, we report that NIK1, which positively regulates plant antiviral immunity, acts as an important negative regulator of antibacterial immunity. nik1 plants exhibit dwarfed morphology, enhanced disease resistance to bacteria and increased PAMP-triggered immunity (PTI) responses, which are restored by NIK1 reintroduction. Additionally, NIK1 negatively regulates the formation of the FLS2/BAK1 complex. The interaction between NIK1 and FLS2/BAK1 is enhanced upon flg22 perception, revealing a novel PTI regulatory mechanism by an RLK. Furthermore, flg22 perception induces NIK1 and RPL10A phosphorylation in vivo, activating antiviral signalling. The NIK1-mediated inverse modulation of antiviral and antibacterial immunity may allow bacteria and viruses to activate host immune responses against each other., Plants deploy numerous receptor-like kinases (RLKs) to respond to pathogens. Here the authors show that NIK1, an RLK that positively regulates antiviral immunity, negatively regulates the response to bacteria by modulating FLS2/BAK1 complex formation, suggesting crosstalk between bacterial and viral immunity.

Mitochondrial 16S rDNA and CO I gene were used as molecular markers for the analysis of the genetic diversity and differentiation of Daphnia galeata populations in nine water bodies in the middle and lower reaches of the Yangtze River. In the combined 16S rDNA and CO I gene sequences, 54 variable sites and 44 haplotypes were observed among 219 individuals belonging to nine D. galeata populations. Average haplotype diversity and nucleotide diversity were, respectively, 0.72% and 0.56%. The F‐statistics (FST) value of the D. galeata populations was 0.149. According to the results of the neutral test, D. galeata in the middle and lower reaches of the Yangtze River had experienced a bottleneck effect in the history. Molecular variance analysis indicated that the genetic differentiation of the D. galeata populations mainly occurred within populations (85.09%). Greater genetic differentiations of D. galeata among individuals within populations appeared in the populations from the Huaihe River basin, whereas smaller genetic differentiations occurred in the populations from the middle reaches of the Yangtze River. Strong gene flows were all observed between Group I (four populations from the middle reaches of the Yangtze River) and Group ΙΙ (three populations from the middle and lower reaches of the Yangtze River), and Group ΙΙΙ (two populations from the Huaihe River basin). The effective migration rates (M) were 851.49 from Group I to Group ΙΙ and 685.96 from Group I to Group ΙΙΙ, respectively. However, no significant relationship was observed between the genetic differentiation and geographical distance of the nine populations (r = .137, p > .05). Results suggested that the genetic differentiation of D. galeata in the water bodies in the middle and lower reaches of the Yangtze River resulted mainly from geographical isolation.

Purpose Restoring lost function to suppressor gene products has captured the interest of the research community in the field of gene therapy. AKAP12, also known as Gravin/AKAP250, is a tumor suppressor gene, and its deregulation may be responsible for cancer progression. The aim of this study was to investigate whether AKAP12 mRNA has an anti-cancer function by regulating onco-miRNA expression in colorectal cancer (CRC) cells. Methods miRNAs targeting AKAP12 were predicted by bioinformatics analysis and further confirmed by dual-luciferase reporter assays and RT-qPCR. The altered expression of microRNA was validated in early-stage CRC tumor tissues by miRseq. Cell proliferation was measured by Cell Counting Kit-8 (CCK-8) assay. Cell invasion and migration were detected by transwell and wound healing assays, respectively. In vivo experiments were conducted to confirm the in vitro findings. Results Among all miRNAs, reversed correlation between AKAP12 expression and miRNA-183-5p expression was most significant. Luciferase assays revealed that AKAP12 directly targeted miR-183-5p. The miRseq data showed that miR-183 was also dysregulated at the early stage of tumor development and upregulated in late sub-stage II CRC patients (P