Immunoglobulin A coating identifies colitogenic bacteria in inflammatory bowel disease.

Specific members of the intestinal microbiota dramatically affect inflammatory bowel disease (IBD) in mice. In humans, however, identifying bacteria that preferentially affect disease susceptibility and severity remains a major challenge. Here, we used flow-cytometry-based bacterial cell sorting and 16S sequencing to characterize taxa-specific coating of the intestinal microbiota with immunoglobulin A (IgA-SEQ) and show that high IgA coating uniquely identifies colitogenic intestinal bacteria in a mouse model of microbiota-driven colitis. We then used IgA-SEQ and extensive anaerobic culturing of fecal bacteria from IBD patients to create personalized disease-associated gut microbiota culture collections with predefined levels of IgA coating. Using these collections, we found that intestinal bacteria selected on the basis of high coating with IgA conferred dramatic susceptibility to colitis in germ-free mice. Thus, our studies suggest that IgA coating identifies inflammatory commensals that preferentially drive intestinal disease. Targeted elimination of such bacteria may reduce, reverse, or even prevent disease development.

Interrogating bromodomain inhibitor resistance in KMT2A-rearranged leukemia through combinatorial CRISPR screens.

Bromo- and extra-terminal domain inhibitors (BETi) have exhibited therapeutic activities in many cancers. However, the mechanisms controlling BETi response and resistance are not well understood. We conducted genome-wide loss-of-function CRISPR screens using BETi-treated KMT2A-rearranged (KMT2A-r) cell lines. We revealed that Speckle-type POZ protein (SPOP) gene (Speckle Type BTB/POZ Protein) deficiency caused significant BETi resistance, which was further validated in cell lines and xenograft models. Proteomics analysis and a kinase-vulnerability CRISPR screen indicated that cells treated with BETi are sensitive to GSK3 perturbation. Pharmaceutical inhibition of GSK3 reversed the BETi-resistance phenotype. Based on this observation, a combination therapy regimen inhibiting both BET and GSK3 was developed to impede KMT2A-r leukemia progression in patient-derived xenografts in vivo. Our results revealed molecular mechanisms underlying BETi resistance and a promising combination treatment regimen of ABBV-744 and CHIR-98014 by utilizing unique ex vivo and in vivo KMT2A-r PDX models.

Activating Mitochondrial Sirtuin 3 in Chondrocytes Alleviates Aging-Induced Fibrocartilage Layer Degeneration and Promotes Healing of Degenerative Rotator Cuff Injury.

The present study aimed to examine the impact of mitochondrial sirtuin 3 (SIRT3) on the degenerative rotator cuff injury, which is a prevalent issue among the elderly population primarily due to aging-related tissue degradation. The study hypothesized that SIRT3, as a major deacetylase in mitochondria, is a significant factor in controlling the quality of mitochondria and the deterioration of fibrocartilage, a crucial component of the rotator cuff. Results showed that the aging process led to weakened biomechanical properties and degeneration of the fibrocartilage layer in mice, accompanied by a decrease in SIRT3 expression. SIRT3 activation ameliorated the aging-related disruption of chondrocyte phenotype and fibrocartilage degradation. SIRT3 activator honokiol improved the phenotype of senescent chondrocytes and promoted rotator cuff healing in aged mice through SIRT3 activation. In conclusion, the findings suggested that the decline in SIRT3 levels with age contributes to rotator cuff degeneration and chondrocyte senescence, and that SIRT3 activation through the use of honokiol is an effective approach for promoting rotator cuff healing in the elderly population.

FIONA1-mediated mRNA m6 A methylation regulates the response of Arabidopsis to salt stress.

N6 -methyladenosine (m6 A) is an mRNA modification widely found in eukaryotes and plays a crucial role in plant development and stress responses. FIONA1 (FIO1) is a recently identified m6 A methyltransferase that regulates Arabidopsis (Arabidopsis thaliana) floral transition; however, its role in stress response remains unknown. In this study, we demonstrate that FIO1-mediated m6 A methylation plays a vital role in salt stress response in Arabidopsis. The loss-of-function fio1 mutant was sensitive to salt stress. Importantly, the complementation lines expressing the wild-type FIO1 exhibited the wild-type phenotype, whereas the complementation lines expressing the mutant FIO1m , in which two critical amino acid residues essential for methyltransferase activity were mutated, did not recover the wild-type phenotype under salt stress, indicating that the salt sensitivity is associated with FIO1 methyltransferase activity. Furthermore, FIO1-mediated m6 A methylation regulated ROS production and affected the transcript level of several salt stress-responsive genes via modulating their mRNA stability in an m6 A-dependent manner in response to salt stress. Importantly, FIO1 is associated with salt stress response by specifically targeting and differentially modulating several salt stress-responsive genes compared with other m6 A writer. Collectively, our findings highlight the molecular mechanism of FIO1-mediated m6 A methylation in the salt stress adaptation.

Extracellular vesicles from UTX-knockout endothelial cells boost neural stem cell differentiation in spinal cord injury.

BACKGROUND: Vascular endothelial cells are pivotal in the pathophysiological progression following spinal cord injury (SCI). The UTX (Ubiquitously Transcribed Tetratripeptide Repeat on Chromosome X) serves as a significant regulator of endothelial cell phenotype. The manipulation of endogenous neural stem cells (NSCs) offers a compelling strategy for the amelioration of SCI. METHODS: Two mouse models were used to investigate SCI: NSCs lineage-traced mice and mice with conditional UTX knockout (UTX KO) in endothelial cells. To study the effects of UTX KO on neural differentiation, we harvested extracellular vesicles (EVs) from both UTX KO spinal cord microvascular endothelial cells (SCMECs) and negative control SCMECs. These EVs were then employed to modulate the differentiation trajectory of endogenous NSCs in the SCI model. RESULTS: In our NSCs lineage-traced mice model of SCI, a marked decrease in neurogenesis was observed post-injury. Notably, NSCs in UTX KO SCMECs mice showed enhanced neuronal differentiation compared to controls. RNA sequencing and western blot analyses revealed an upregulation of L1 cell adhesion molecule (L1CAM), a gene associated with neurogenesis, in UTX KO SCMECs and their secreted EVs. This aligns with the observed promotion of neurogenesis in UTX KO conditions. In vivo administration of L1CAM-rich EVs from UTX KO SCMECs (KO EVs) to the mice significantly enhanced neural differentiation. Similarly, in vitro exposure of NSCs to KO EVs resulted in increased activation of the Akt signaling pathway, further promoting neural differentiation. Conversely, inhibiting Akt phosphorylation or knocking down L1CAM negated the beneficial effects of KO EVs on NSC neuronal differentiation. CONCLUSIONS: In conclusion, our findings substantiate that EVs derived from UTX KO SCMECs can act as facilitators of neural differentiation following SCI. This study not only elucidates a novel mechanism but also opens new horizons for therapeutic interventions in the treatment of SCI. Video Abstract.

Biosynthesis of Bt-Ag2O nanoparticles using Bacillus thuringiensis and their pesticidal and antimicrobial activities.

Nanosilver oxide exhibits strong antibacterial and photocatalytic properties and has shown great application potential in food packaging, biochemical fields, and other fields involving diseases and pest control. In this study, Ag2O nanoparticles were synthesized using Bacillus thuringiensis (Bt-Ag2O NPs). The physicochemical characteristics of the Bt-Ag2O NPs were analyzed by UV‒vis spectroscopy, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscope (SEM), inductively coupled plasma emission spectrometry (ICP), high-resolution transmission electron microscopy (HR-TEM), and zeta potential. The phis-chemical characterization revealed that the Bt-Ag2O NPs are in spherical shape with the small particle size (18.24 nm), high crystallinity, well dispersity, and stability. The biopesticidal and antifungal effects of Bt-Ag2O NPs were tested against Tribolium castaneum, Aspergillus flavus, and Penicillium chrysogenum. The survival, growth, and reproduction of tested pests and molds were significantly inhibited by Bt-Ag2O NPs in a dose-dependent manner. Bt-Ag2O NPs showed higher pesticidal activities against T. castaneum than Bt and commercial Ag2O NPs. The LC50 values of Bt, Ag2O NPs, and Bt-Ag2O NPs were 0.139%, 0.072%, and 0.06% on day 14, respectively. The Bt-Ag2O NPs also showed well antifungal activities against A. flavus and P. chrysogenum, while it resulted a small inhibition zone than commercial Ag2O NPs did. In addition, A. flavus showed much more sensitive to Bt-Ag2O NP treatments, compared to P. chrysogenum. Our results revealed that Bt-Ag2O NPs synthesized using B. thuringiensis could act as pesticides and antifungal agents in stored-product fields. KEY POINTS: • Bt-Ag2O NPs could be synthesized using Bacillus thuringiensis (Bt). • The NPs showed a high degree of crystallinity, spherical shape, and small particle size. • The NPs also showed excellent insecticidal and antifungal activity.

Hypoxia-treated adipose mesenchymal stem cell-derived exosomes attenuate lumbar facet joint osteoarthritis.

BACKGROUND: Lumbar facet joint osteoarthritis (LFJ OA) is a common disease, and there is still a lack of effective disease-modifying therapies. Our aim was to determine the therapeutic effect of hypoxia-treated adipose mesenchymal stem cell (ADSC)-derived exosomes (Hypo-ADSC-Exos) on the protective effect against LFJ OA. METHODS: The protective effect of Hypo-ADSC-Exos against LFJ OA was examined in lumbar spinal instability (LSI)-induced LFJ OA models. Spinal pain behavioural assessments and CGRP (Calcitonin Gene-Related Peptide positive) immunofluorescence were evaluated. Cartilage degradation and subchondral bone remodelling were assessed by histological methods, immunohistochemistry, synchrotron radiation-Fourier transform infrared spectroscopy (SR-FTIR), and 3D X-ray microscope scanning. RESULTS: Hypoxia enhanced the protective effect of ADSC-Exos on LFJ OA. Specifically, tail vein injection of Hypo-ADSC-Exos protected articular cartilage from degradation, as demonstrated by lower FJ OA scores of articular cartilage and less proteoglycan loss in lumbar facet joint (LFJ) cartilage than in the ADSC-Exo group, and these parameters were significantly improved compared to those in the PBS group. In addition, the levels and distribution of collagen and proteoglycan in LFJ cartilage were increased in the Hypo-ADSC-Exo group compared to the ADSC-Exo or PBS group by SR-FTIR. Furthermore, Hypo-ADSC-Exos normalized uncoupled bone remodelling and aberrant H-type vessel formation in subchondral bone and effectively reduced symptomatic spinal pain caused by LFJ OA in mice compared with those in the ADSC-Exo or PBS group. CONCLUSIONS: Our results show that hypoxia is an effective method to improve the therapeutic effect of ADSC-Exos on ameliorating spinal pain and LFJ OA progression.

Inhibition of UTX/KDM6A improves recovery of spinal cord injury by attenuating BSCB permeability and macrophage infiltration through the MLCK/p-MLC pathway.

Spinal cord injury (SCI) can prompt an immediate disruption to the blood-spinal cord barrier (BSCB). Restoring the integrity of this barrier is vital for the recovery of neurological function post-SCI. The UTX protein, a histone demethylase, has been shown in previous research to promote vascular regeneration and neurological recovery in mice with SCI. However, it is unclear whether UTX knockout could facilitate the recovery of the BSCB by reducing its permeability. In this study, we systematically studied BSCB disruption and permeability at different time points after SCI and found that conditional UTX deletion in endothelial cells (ECs) can reduce BSCB permeability, decrease inflammatory cell infiltration and ROS production, and improve neurological function recovery after SCI. Subsequently, we used RNA sequencing and ChIP-qPCR to confirm that conditional UTX knockout in ECs can down-regulate expression of myosin light chain kinase (MLCK), which specifically mediates myosin light chain (MLC) phosphorylation and is involved in actin contraction, cell retraction, and tight junctions (TJs) protein integrity. Moreover, we found that MLCK overexpression can increase the ratio of p-MLC/MLC, further break TJs, and exacerbate BSCB deterioration. Overall, our findings indicate that UTX knockout could inhibit the MLCK/p-MLC pathway, resulting in decreased BSCB permeability, and ultimately promoting neurological recovery in mice. These results suggest that UTX is a promising new target for treating SCI.

Endothelial progenitor cell-derived exosomes promote anti-inflammatory macrophages via SOCS3/JAK2/STAT3 axis and improve the outcome of spinal cord injury.

BACKGROUND: Macrophage in the spinal cord injury (SCI) area imparts a chronic pro-inflammation effect that challenges the recovery of SCI. Previously, endothelial progenitor cell-produced exosomes (EPC-EXOs) have been noticed to facilitate revascularization and inflammation control after SCI. However, their effects on macrophage polarization remained unclear. This study aimed to investigate the EPC-EXOs' role in macrophage polarization and reveal its underlying mechanism. METHODS: We extracted the macrophages and EPC from the bone marrow suspension of C57BL/L mice by centrifugation. After cell identification, the EPC-EXOs were collected by ultra-high-speed centrifugation and exosome extraction kits and identified by transmission electron microscopy and nanoparticle tracking analysis. Then, macrophages were cultured with EPC-EXOs in different concentrations. We labeled the exosome to confirm its internalization by macrophage and detected the macrophage polarization marker level both in vitro and in vivo. We further estimated EPC-EXOs' protective effects on SCI by mice spinal cord tissue H&E staining and motor behavior evaluation. Finally, we performed RT-qPCR to identify the upregulated miRNA in EPC-EXOs and manipulate its expression to estimate its role in macrophage polarization, SOCS3/JAK2/STAT3 pathway activation, and motor behavior improvement. RESULTS: We found that EPC-EXOs decreased the macrophages' pro-inflammatory marker expression and increased their anti-inflammatory marker expression on the 7 and 14 days after SCI. The spinal cord H&E staining results showed that EPC-EXOs raised the tissue-sparing area rate significantly after 28 days of SCI and the motor behavior evaluation indicated an increased BMS score and motor-evoked potential by EPC-EXOs treatment after SCI. The RT-qPCR assay identified that miR-222-3P upregulated in EPC-EXOs and its miRNA-mimic also decreased the pro-inflammatory macrophages and increased the anti-inflammatory macrophages. Additionally, miR-222-3P mimic activated the SOCS3/JAK2/STAT3 pathway, and SOCS3/JAK2/STAT3 pathway inhibition blocked miR-2223P's effects on macrophage polarization and mouse motor behavior. CONCLUSION: Comprehensively, we discovered that EPC-EXOs-derived miR-222-3p affected macrophage polarization via SOCS3/JAK2/STAT3 pathway and promoted mouse functional repair after SCI, which reveals EPC-EXOs' role in modulation of macrophage phenotype and will provide a novel interventional strategy to induce post-SCI recovery.

Unique features of mRNA m6A methylomes during expansion of tomato (Solanum lycopersicum) fruits.

N6-methyladenosine (m6A) is the most abundant internal modification in eukaryotic messenger RNA. Although the role of m6A has been demonstrated in many biological processes, including embryonic development, flowering time control, microspore generation, fruit ripening, and stress responses, its contribution to other aspects of plant development still needs to be explored. Herein, we show the potential link between m6A deposition and the expansion of tomato (Solanum lycopersicum) fruits through parallel m6A-immunoprecipitation-sequencing (m6A-seq) and RNA-seq analyses. We found that global m6A levels increased during tomato fruit expansion from immature green to mature green stage. m6A-seq revealed that thousands of protein-coding genes are m6A-modified mainly in the 3'-untranslated regions. m6A-seq and RNA-seq analyses showed a positive association between m6A methylation and mRNA abundance. In particular, a large number of fruit expansion-related genes involved in hormone responses and endoreduplication were m6A modified and expressed more actively than the non-m6A-modified genes, suggesting a potential role of m6A modification in tomato fruit expansion. Importantly, altering m6A levels by direct injection of 3-deazaneplanocin A (DA; m6A writer inhibitor) or meclofenamic acid (MA; m6A eraser inhibitor) into tomato fruits suppressed fruit expansion; however, injection of exogenous DA or MA accelerated or delayed fruit ripening, respectively. Collectively, these results suggest a dynamic role of m6A methylation in the expansion and ripening of tomato fruits.

Arabidopsis N6-methyladenosine methyltransferase FIONA1 regulates floral transition by affecting the splicing of FLC and the stability of floral activators SPL3 and SEP3.

N 6-methyladenosine (m6A) RNA methylation has been shown to play a crucial role in plant development and floral transition. Two recent studies have identified FIONA1 as an m6A methyltransferase that regulates the floral transition in Arabidopsis through influencing the stability of CONSTANS (CO), SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 (SOC1), and FLOWERING LOCUS C (FLC). In this study, we confirmed that FIONA1 is an m6A methyltransferase that installs m6A marks in a small group of mRNAs. Furthermore, we show that, in addition to its role in influencing the stability of CO, SOC1, and FLC, FIONA1-mediated m6A methylation influences the splicing of FLC, a key floral repressor, and the stability of SQUAMOSA PROMOTER-BINDING PROTEIN-LIKE 3 (SPL3) and SEPALLATA3 (SEP3), floral activators, which together play a vital role in floral transition in Arabidopsis. Our study confirms the function of FIONA1 as an m6A methyltransferase and suggests a close molecular link between FIONA1-mediated m6A methylation and the splicing of FLC and the destabilization of SPL3 and SEP3 in flowering time control.

UTX deletion promotes M2 macrophage polarization by epigenetically regulating endothelial cell-macrophage crosstalk after spinal cord injury.

Macrophages polarized to the M2 subtype after spinal cord injury (SCI) are beneficial for promoting neurological recovery. The crosstalk between endothelial cells (ECs) and macrophages is crucial for the imbalance between proinflammatory and pro-resolving responses caused by macrophage heterogeneity; however, this crosstalk is strengthened post-SCI, leading to inflammatory cascades and second damage. As a powerful means to regulate gene expression, epigenetic regulation of the interaction between immune cells and ECs in SCI is still largely unknown. Our previous research demonstrated that the histone demethylase UTX deletion in ECs (UTX-/- ECs) promotes neurological recovery, while the precise mechanism is unrevealed. Here, we discovered that UTX-/- ECs polarize macrophages toward the M2 subtype post-SCI. Macrophage deficiency could block the neurological recovery caused by the knockdown of UTX. The exosomes from UTX-/- ECs mediate this crosstalk. In addition, we found UTX, H3K27, and miR-467b-3p/Sfmbt2 promoters forming a regulatory complex that upregulates the miR-467b-3p in UTX-/- ECs. And then, miR-467b-3p transfers to macrophages by exosomes and activates the PI3K/AKT/mTOR signaling by decreasing PTEN expression, finally polarizing macrophage to the M2 subtype. This study reveals a mechanism by epigenetic regulation of ECs-macrophages crosstalk and identifies potential targets, which may provide opportunities for treating SCI.

Spondylodiscitis of lumbar complicated with spinal epidural abscess caused by Parvimonas micra: A case report and literature review. / å¾®å°å°å•èƒžèŒè °æ¤Žé—´ç›˜ç‚Žå¹¶æ¤Žç®¡å† ç¡¬è†œå¤–è„“è‚¿1例及文献回顾.

Spinal infection caused by Parvimonas micra (P. micra) is a rare infection. The characteristic imageology includes spondylodiscitis, spondylitis, paravertebral abscess, and epidural abscess. One case of spondylodiscitis of lumbar complicated with spinal epidural abscess caused by P. micra was admitted to the Department of Spinal Surgery, Xiangya Hospital, Central South University on February, 2023. This case is a 60 years old man with lower back pain and left lower limb numbness. MRI showed spondylitis, spondylodiscitis, and epidural abscess. The patient underwent debridement, decompression and fusion surgery. The culture of surgical sample was negative. P. micra was detected by metagenomic next-generation sequencing (mNGS). The postoperative antibiotic treatment included intravenous infusion of linezolid and piperacillin for 1 week, then intravenous infusion of ceftazidime and oral metronidazole for 2 weeks, followed by oral metronidazole and nerofloxacin for 2 weeks. During the follow-up, the lower back pain and left lower limb numbness was complete remission. Spinal infection caused by P. micra is extremely rare, when the culture is negative, mNGS can help the final diagnosis.

Construction and verification of a quantitative index system to evaluate the medical and nursing care for the elderly service needs. / è€å¹´äººåŒ»å »æœåŠ¡éœ€æ±‚é‡åŒ–è¯„ä¼°æŒ‡æ ‡ä½“ç³»çš„æž„å»ºä¸ŽéªŒè¯.

OBJECTIVES: To construct a quantitative index system with the integrated medical and nursing care assessment for the elderly service needs, this system can assess the cost of medical and care services accurately and objectively, so as to provide scientific basis for the allocation of old-age service resources in China. METHODS: Based on the survival needs of the Existence, Relation and Growth theory, an index system is constructed through literature analysis, group discussion, and expert correspondence. Analytic hierarchy process was used to determine the weights of indicators at all levels. The 3-grades service items corresponding to each index were quantified through the measurement of working hours, and the medical and nursing care needs of 624 disabled/demented elderly people over 60 years old in Changsha were investigated to evaluate their reliability and validity. RESULTS: The authoritative coefficients of the 2 rounds of expert correspondence were 88.5% and 88.6%, respectively, and the opinion coordination coefficients were 0.159 and 0.167, respectively. The final quantitative evaluation index system included 4 first-level indicators, 17 second-level indicators, and 105 third-level indicators. The service time of doctor ranged from 6.01 to 22.64 min, the service time of nurses ranged from 0.77 to 24.79 min, and the service time of caregiver ranged from 0.12 to 51.88 min. The Cronbach's αcoefficient was 0.73, the split-half reliability was 0.74, the content validity was 0.93, and the calibration validity was 0.781. CONCLUSIONS: The quantitative evaluation index system of medical and nursing service need for the elderly can be used to accurately evaluate the medical and nursing service need.

N6 -Methyladenosine mRNA methylation is important for salt stress tolerance in Arabidopsis.

As the most abundant internal modification of mRNA, N6 -methyladenosine (m6 A) methylation of RNA is emerging as a new layer of epitranscriptomic gene regulation in cellular processes, including embryo development, flowering-time control, microspore generation and fruit ripening, in plants. However, the cellular role of m6 A in plant responses to environmental stimuli remains largely unexplored. In this study, we show that m6 A methylation plays an important role in salt stress tolerance in Arabidopsis. All mutants of m6 A writer components, including MTA, MTB, VIRILIZER (VIR) and HAKAI, displayed salt-sensitive phenotypes in an m6 A-dependent manner. The vir mutant, in which the level of m6 A was most highly reduced, exhibited salt-hypersensitive phenotypes. Analysis of the m6 A methylome in the vir mutant revealed a transcriptome-wide loss of m6 A modification in the 3' untranslated region (3'-UTR). We demonstrated further that VIR-mediated m6 A methylation modulates reactive oxygen species homeostasis by negatively regulating the mRNA stability of several salt stress negative regulators, including ATAF1, GI and GSTU17, through affecting 3'-UTR lengthening linked to alternative polyadenylation. Our results highlight the important role played by epitranscriptomic mRNA methylation in the salt stress response of Arabidopsis and indicate a strong link between m6 A methylation and 3'-UTR length and mRNA stability during stress adaptation.

Longitudinal Changes in Fecal Calprotectin Levels Among Pregnant Women With and Without Inflammatory Bowel Disease and Their Babies.

BACKGROUND & AIMS: The effect of pregnancy on inflammatory bowel disease (IBD) remains poorly understood. We aimed to monitor intestinal inflammation using fecal calprotectin (FC) in pregnant women and their babies during early life. METHODS: Pregnant women with or without IBD and their infants were prospectively enrolled. FC levels were measured at each trimester of pregnancy and in babies throughout the first 3 years of life. Repeated-measures analysis was applied to investigate changes in FC levels while adjusting for confounders. The FC levels were correlated with the bacterial abundance in both mothers and babies. RESULTS: Six hundred and fourteen fecal samples from 358 mothers (98 with IBD) and 1005 fecal samples from 289 infants (76 born to IBD mothers) were analyzed. Pregnant Patients with IBD maintained higher FC levels through pregnancy compared with controls (P = 7.5 × 10-54). FC gradually increased in controls and declined in Patients with IBD throughout pregnancy (P for interaction = 5.8 × 10-7). Babies born to mothers with IBD presented with significantly higher FC levels than those born to controls up to 3 years of age, after adjusting for sex, delivery mode, feeding behavior, and antibiotics exposure (2 weeks to 3 months of age, P = .015; 12-36 months of age, P = .00003). Subdoligranulum, Roseburia, Fusicatenibacter, and Alistipes negatively correlated, and Streptococcus, Prevotella, Escherichia-Shigella, and Bifidobacterium positively correlated with maternal FC levels at T3. Faecalibacterium, Bifidobacterium, and Alistipes showed negative correlations, and Streptococcus were positively correlated with FC levels within 3 months of birth. CONCLUSIONS: Pregnancy is associated with decreased inflammatory activity in mothers with IBD. Higher FC levels in babies born to mothers with IBD suggest subclinical inflammation in early life, the long-term consequences of which are uncertain.

Identification of the key flavonoid and lipid synthesis proteins in the pulp of two sea buckthorn cultivars at different developmental stages.

BACKGROUND: Sea buckthorn is an economically important woody plant for desertification control and water soil conservation. Its berry pulp is rich in flavonoids and unsaturated fatty acids. Cultivars containing high oil and flavonoid contents have higher economic value and will increase in the planting area. However, the cause of the differences in oil and flavonoid contents among cultivars is still unclear. The influence of key enzymes in the lipid and flavonoid synthesis pathways on their content needs to be explored and clarified. RESULTS: The flavonoid content in XE (Xin'e 3) was 54% higher than that in SJ (Suiji 1). Rutin was the main flavonoid in sea buckthorn pulp, and the differences in the rutin content could cause flavonoid differences between the two cultivars. The oil content of XE was 31.58% higher than that of SJ, and the difference in oil content was highest at 50-70 DAF. High-throughput proteomics was used to quantify key enzymes of flavonoid and lipid synthesis pathways in two cultivars at three developmental stages. By functional annotation and KEGG analysis, 41 key enzymes related to phenylpropanoid biosynthesis, flavonoid biosynthesis, flavone and flavonol biosynthesis, fatty acid biosynthesis and TAG biosynthesis were quantified. CHS, F3H, ANS, fabD, FATA, FAB2, LPIN and plcC showed significant differences between the two cultivars. In addition, we quantified 6 oleosins. With the exception of a 16 kDa oleosin, the other oleosins in the two cultivars were positively correlated with oil content. CONCLUSIONS: In the flavonoid synthesis pathway, CHS and F3H were the main enzymes responsible for the difference in flavonoid content between the two cultivars. In the lipid synthesis pathway, LPIN, plcC and MGD were the main enzymes with different contents in the middle to late stages. Higher contents of LPIN and plcC in XE than in SJ could cause DAG to generate TAG from PC, since the difference in DGAT between the two cultivars was not significant. Investigating the causes of flavonoid and oil content differences among different cultivars from the perspective of proteomics, could provide a basis for understanding the regulatory mechanism of flavonoids and lipid synthesis in sea buckthorn pulp.

Epitranscriptomic mRNA modifications governing plant stress responses: underlying mechanism and potential application.

Plants inevitably encounter environmental adversities, including abiotic and biotic stresses, which significantly impede plant growth and reduce crop yield. Thus, fine-tuning the fate and function of stress-responsive RNAs is indispensable for plant survival under such adverse conditions. Recently, post-transcriptional RNA modifications have been studied as a potent route to regulate plant gene expression under stress. Among over 160 mRNA modifications identified to date, N6 -methyladenosine (m6 A) in mRNAs is notable because of its multifaceted roles in plant development and stress response. Recent transcriptome-wide mapping has revealed the distribution and patterns of m6 A in diverse stress-responsive mRNAs in plants, building a foundation for elucidating the molecular link between m6 A and stress response. Moreover, the identification and characterization of m6 A writers, readers and erasers in Arabidopsis and other model crops have offered insights into the biological roles of m6 A in plant abiotic stress responses. Here, we review the recent progress of research on mRNA modifications, particularly m6 A, and their dynamics, distribution, regulation and biological functions in plant stress responses. Further, we posit potential strategies for breeding stress-tolerant crops by engineering mRNA modifications and propose the future direction of research on RNA modifications to gain a much deeper understanding of plant stress biology.

3D visualization and morphometric analysis of spinal motion segments and vascular networks: A synchrotron radiation-based micro-CT study in mice.

The structure of spinal motion segments and spinal vasculature is complicated. Visualizing the three-dimensional (3D) structure of the spine may provide guidance for spine surgery. However, conventional imaging techniques fail to simultaneously obtain 3D images of soft and hard tissues, and achieving such coimaging states of the spine and its vascular networks remains a challenge. Synchrotron radiation micro-CT (SRµCT) provides a relatively effective and novel method of acquiring detailed 3D information. In this study, specimens of the thoracic spine were obtained from six mice. SRµCT was employed to acquire 3D images of the structure, and histologic staining was performed for comparisons with the SRµCT images. The whole spinal motion segments and the spinal vascular network were simultaneously explored at high resolution. The mean thickness of the cartilaginous end plates (CEPs) and the volume of the intervertebral discs (IVDs) were calculated. The surface of the CEPs and the facet joint cartilage (FJC) were presented as heat maps, which allowed for direct visualization of the thickness distribution. Regional division revealed heterogeneity among the ventral, central, and dorsal parts of the CEPs and between the superior and inferior parts of the facet processes. Moreover, the connections and spatial morphology of the spinal vascular network were visualized. Our study indicates that SRµCT imaging is an ideal method for high-resolution visualization and 3D morphometric analysis of the whole spinal motion segments and spinal vascular network.

Breastfeeding Is Associated with Lower Likelihood of Helicobacter Pylori Colonization in Babies, Based on a Prospective USA Maternal-Infant Cohort.

BACKGROUND: Mother-to-child transmission of Helicobacter pylori (H. pylori) is the primary source of intrafamilial spread in early childhood in regions of high H. pylori prevalence. However, early-in-life H. pylori colonization and associated protective or risk factors have not been fully evaluated in lower prevalence regions, such as the USA. AIMS: Therefore, from a well-characterized prospective US cohort, we selected women who provided fecal samples during pregnancy and had paired fecal samples from their babies up to 24 months postpartum. We evaluated maternal and baby factors associated with likelihood of H. pylori colonization in the babies. Fecal antigen testing was used to determine H. pylori status. We also evaluated the association between maternal breastmilk cytokines and H. pylori colonization in breastfed babies. RESULTS: Among included mother-baby pairs (n = 66), H. pylori prevalence was 31.8% in mothers and 19.7% in their babies. Dominant breastfeeding (adjusted odds ratio [aOR] 0.17, 95% CI 0.03-0.98) and maternal IBD (aOR 0.05, 95% CI 0.01-0.27) were associated with significantly lower likelihood of H. pylori colonization among babies; no other clinical factors were associated with H. pylori colonization in the babies. Matrix metalloproteinase-10 (MMP-10) and tumor necrosis factor-related activation-induced cytokine expression were significantly higher in breastmilk of mothers with H. pylori positive vs negative babies. CONCLUSIONS: Consistent with data from high H. pylori prevalence regions, our findings suggest dominant breastfeeding may protect against early H. pylori colonization. Downregulation of pro-inflammatory cytokines such as MMP-10 may be relevant in mediating this protection among breastfed babies, but more data are needed.