Opposite Roles of Salicylic Acid Receptors NPR1 and NPR3/NPR4 in Transcriptional Regulation of Plant Immunity.

Salicylic acid (SA) is a plant defense hormone required for immunity. Arabidopsis NPR1 and NPR3/NPR4 were previously shown to bind SA and all three proteins were proposed as SA receptors. NPR1 functions as a transcriptional co-activator, whereas NPR3/NPR4 were suggested to function as E3 ligases that promote NPR1 degradation. Here we report that NPR3/NPR4 function as transcriptional co-repressors and SA inhibits their activities to promote the expression of downstream immune regulators. npr4-4D, a gain-of-function npr4 allele that renders NPR4 unable to bind SA, constitutively represses SA-induced immune responses. In contrast, the equivalent mutation in NPR1 abolishes its ability to bind SA and promote SA-induced defense gene expression. Further analysis revealed that NPR3/NPR4 and NPR1 function independently to regulate SA-induced immune responses. Our study indicates that both NPR1 and NPR3/NPR4 are bona fide SA receptors, but play opposite roles in transcriptional regulation of SA-induced defense gene expression.

Potential Approach to Quantifying the Volume of the Ischemic Core in Truncated Computed Tomography Perfusion Scans: A Preliminary Study.

OBJECTIVE: This study aimed to provide an alternative approach for quantifying the volume of the ischemic core (IC) if truncation of computed tomography perfusion (CTP) occurs in clinical practice. METHODS: Baseline CTP and follow-up diffusion-weighted imaging (DWI) data from 88 patients with stroke were retrospectively collected. CTP source images (CTPSI) from the unenhanced phase to the peak arterial phase (CTPSI-A) or the peak venous phase (CTPSI-V) were collected to simulate the truncation of CTP in the arterial or venous phases, respectively. The volume of IC on CTPSI-A (V CTPSI-A ) or CTPSI-V (V CTPSI-V ) was defined as the volume of the brain tissue with >65% reduction in attenuation compared with that of the normal tissue. The volume of IC on the baseline CTP (V CTP ) was defined as a relative cerebral blood flow of <30% of that in the normal tissue. The volume of the posttreatment infarct on the follow-up DWI (V DWI ) image was manually delineated and calculated. One-way analysis of variance, Bland-Altman plots, and Spearman correlation analyses were used for the statistical analysis. RESULTS: V CTPSI-A was significantly higher than V DWI ( P < 0.001); however, no significant difference was observed between V CTP and V DWI ( P = 0.073) or between V CTPSI-V and V DWI ( P > 0.999). The mean differences between V DWI and V CTPSI-V , V DWI and V CTP , and V DWI and V CTPSI-A were 1.70 mL (limits of agreement [LoA], -56.40 to 59.70), 8.30 mL (LoA, -40.70 to 57.30), and -68.10 mL (LoA, -180.90 to 44.70), respectively. Significant correlations were observed between V DWI and V CTP ( r = 0.68, P < 0.001) and between V DWI and V CTPSI-V ( r = 0.39, P < 0.001); however, no significant correlation was observed between V DWI and V CTPSI-A ( r = 0.20, P = 0.068). CONCLUSIONS: V CTPSI-V may be a promising method for quantifying the volume of the IC if truncation of CTP occurs.

Spatial accuracy of computed tomography perfusion to estimate the follow-up infarct on diffusion-weighted imaging after successful mechanical thrombectomy.

BACKGROUND: Volumetric accuracy of using computed tomography perfusion (CTP) to estimate the post-treatment infarct in stroke patients with successful recanalization after mechanical thrombectomy (MT) has been studied a lot, however the spatial accuracy and its influence factors has not been fully investigated. METHODS: This retrospective study reviewed the data from consecutive anterior large vessel occlusion (LVO) patients who had baseline CTP, successful recanalization after MT, and post-treatment diffusion-weighed imaging (DWI). Ischemic core on baseline CTP was estimated using relative cerebral blood flood (CBF) of < 30%. The infarct area was outlined manually on post-treatment DWI, and registered to CTP. Spatial agreement was assessed using the Dice similarity coefficient (DSC) and average Hausdorff distance. According to the median DSC, the study population was dichotomized into high and low Dice groups. Univariable and multivariable regression analyses were used to determine the factors independently associated with the spatial agreement. RESULTS: In 72 included patients, the median DSC was 0.26, and the median average Hausdorff distance was 1.77 mm. High Dice group showed significantly higher median ischemic core volume on baseline CTP (33.90 mL vs 3.40 mL, P < 0.001), lower proportion of moderate or severe leukoaraiosis [27.78% vs 52.78%, P = 0.031], and higher median infarct volume on follow-up DWI (51.17 mL vs 9.42 mL, P < 0.001) than low Dice group. Ischemic core volume on baseline CTP was found to be independently associated with the spatial agreement (OR, 1.092; P < 0.001). CONCLUSIONS: CTP could help to spatially locate the post-treatment infarct in anterior LVO patients who achieving successful recanalization after MT. Ischemic core volume on baseline CTP was independently associated with the spatial agreement.

CT perfusion with increased temporal sampling interval to predict target mismatch status in patients with acute ischemic stroke.

PURPOSE: To evaluate the feasibility of using CT perfusion (CTP) with increased temporal sampling interval to predict the target mismatch status in acute ischemic stroke (AIS) patients with anterior circular large-vessel occlusion (LVO). METHODS: CTP with a sampling interval of 1.7 s (CTP1.7 s) was scanned in 77 AIS patients for pre-treatment evaluation. Simulated CTP data with sampling interval of 3.4 s (CTP3.4 s) or 5.1 s (CTP5.1 s) were reconstructed, respectively. Target mismatch was defined according to the EXTEND-IA (Extending the Time for Thrombolysis in Emergency Neurological Deficits-Intra-Arterial) and DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke) trial criteria, respectively. Pearson correlation analysis, Mann-Whitney U test, Bland-Altman analysis, and chi-square test were used for statistical analysis as appropriate. RESULTS: Significant correlations were found on the volume of ischemic core, hypo-perfused area, mismatch area, and ratio between CTP1.7 s and CTP3.4 s or CTP5.1 s (all p < 0.001). There was no significant difference on the volume of ischemic core, hypo-perfused area, mismatch area, and mismatch ratio between CTP1.7 s and CTP3.4 s or CTP5.1 s (all p > 0.05). Compared with CTP1.7 s, CTP3.4 s or CTP5.1 s showed comparable performance in predicting the target mismatch status in the AIS patients with LVO (both p > 0.05). CONCLUSIONS: CTPs with increased temporal sampling intervals that lead to reduced radiation doses are feasible and may provide comparable performance in predicting target mismatch status in AIS patients with LVO.

The Biological Implication of Semicarbazide-Sensitive Amine Oxidase (SSAO) Upregulation in Rat Systemic Inflammatory Response under Simulated Aerospace Environment.

The progress of space science and technology has ushered in a new era for humanity's exploration of outer space. Recent studies have indicated that the aerospace special environment including microgravity and space radiation poses a significant risk to the health of astronauts, which involves multiple pathophysiological effects on the human body as well on tissues and organs. It has been an important research topic to study the molecular mechanism of body damage and further explore countermeasures against the physiological and pathological changes caused by the space environment. In this study, we used the rat model to study the biological effects of the tissue damage and related molecular pathway under either simulated microgravity or heavy ion radiation or combined stimulation. Our study disclosed that ureaplasma-sensitive amino oxidase (SSAO) upregulation is closely related to the systematic inflammatory response (IL-6, TNF-α) in rats under a simulated aerospace environment. In particular, the space environment leads to significant changes in the level of inflammatory genes in heart tissues, thus altering the expression and activity of SSAO and causing inflammatory responses. The detailed molecular mechanisms have been further validated in the genetic engineering cell line model. Overall, this work clearly shows the biological implication of SSAO upregulation in microgravity and radiation-mediated inflammatory response, providing a scientific basis or potential target for further in-depth investigation of the pathological damage and protection strategy under a space environment.

[MinerVa: A high performance bioinformatic algorithm for the detection of minimal residual disease in solid tumors].

How to improve the performance of circulating tumor DNA (ctDNA) signal acquisition and the accuracy to authenticate ultra low-frequency mutation are major challenges of minimal residual disease (MRD) detection in solid tumors. In this study, we developed a new MRD bioinformatics algorithm, namely multi-variant joint confidence analysis (MinerVa), and tested this algorithm both in contrived ctDNA standards and plasma DNA samples of patients with early non-small cell lung cancer (NSCLC). Our results showed that the specificity of multi-variant tracking of MinerVa algorithm ranged from 99.62% to 99.70%, and when tracking 30 variants, variant signals could be detected as low as 6.3 × 10 -5 variant abundance. Furthermore, in a cohort of 27 NSCLC patients, the specificity of ctDNA-MRD for recurrence monitoring was 100%, and the sensitivity was 78.6%. These findings indicate that the MinerVa algorithm can efficiently capture ctDNA signals in blood samples and exhibit high accuracy in MRD detection.

On-treatment blood TMB as predictors for camrelizumab plus chemotherapy in advanced lung squamous cell carcinoma: biomarker analysis of a phase III trial.

BACKGROUND: Camrelizumab plus chemotherapy significantly prolonged progression-free survival (PFS) and overall survival (OS) compared to chemotherapy alone as first-line treatment in advanced lung squamous cell carcinoma (LUSC) in the phase III trial (CameL-sq), which has become an option of standard-of-cares for Chinese patients with advanced LUSC. However, the predictive biomarkers remain unknown. METHODS: Tumor tissue samples at baseline, and peripheral blood samples at baseline (pretreatment) and after two cycles of treatment (on-treatment) were prospectively collected from 270 LUSC patients from the CameL-sq study. Blood tumor mutation burden (bTMB) and its dynamics were analyzed to explore their predictive values. RESULTS: Pretreatment bTMB was not associated with objective response, PFS and OS in camrelizumab or placebo plus chemotherapy groups. Low on-treatment bTMB was associated with significantly better objective response (73.8% vs 27.8%, P < 0.001), PFS (median, 9.1 vs 4.1 months; P < 0.001) and OS (median, not reached vs 8.0 months; P < 0.001) in camrelizumab plus chemotherapy group whereas it did not correlate with objective response and PFS in chemotherapy alone group. Importantly, on-treatment bTMB level could discriminate patients of initially radiological stable disease who would long-term benefit from camrelizumab plus chemotherapy (low vs high, median OS, 18.2 vs 7.8 months; P = 0.001). Combing on-treatment bTMB and its dynamics improved the ability for predicting the efficacy of camrelizumab plus chemotherapy. CONCLUSION: On-treatment bTMB together with its dynamics could serve as a predictive biomarker for camrelizumab plus chemotherapy in patients with advanced LUSC. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03668496.

The systemic characterization of aptamer cocktail for bacterial detection studied by graphene oxide-based fluorescence resonance energy transfer aptasensor.

Aptamers have gained significant attention as the molecular recognition element to replace antibodies in sensor development and target delivery. Nevertheless, it is noteworthy that unlike the wide application of polyvalent antibodies, existing researches on the combined use of heterologous aptamers with similar recognition affinity and specificity for target detection were sporadic. Herein, first, the wide existence of polyaptamer for bacteria was revealed through the summary of existing literature. Furthermore, based on the establishment of a sensitive aptamer cocktail/graphene oxide fluorescence resonance energy transfer polyaptasensor with a detection limit as low as 10 CFU/ml, the systemic characterization of aptamer cocktails in bacterial detection was carried out by taking E. coli, Vi. parahemolyticus, S. typhimurium, and C. sakazakii as the assay targets. It was turned out that the polyaptasensors for C. sakazakii and S. typhimurium owned prevalence in the broader concentration range of target bacteria. While the polyaptasensors for E. coli and V. parahemolyticus outperformed monoaptasensor mainly in the lower concentration of target bacteria. The linear relationships between fluorescence recovery and the concentration of bacteria were also discussed. The different characteristics of the bacterial cellular membrane, including the binding affinity and the robustness to variation, are analyzed to be the main reason for the diverse detection performance of aptasensors. The study here enhances a sensor detection strategy with super sensitivity. More importantly, this systemic study on the aptamer cocktail in reference to antibodies will advance the in-depth understanding and rational design of aptamer based biological recognition, detection, and targeting.

Paraliobacillus salinarum sp. nov., isolated from saline soil in Yingkou, China.

A novel Gram-stain-positive, facultatively aerobic, slightly halophilic, endospore-forming bacterium, designated G6-18T, was isolated from saline soil collected in Yingkou, Liaoning, PR China. Cells of strain G6-18T grew at 10-37 °C (optimum, 30 °C), at pH 6.0-9.0 (optimum, pH 8.0) and in the presence of 2-15 % (w/v) NaCl (optimum, 5 %). The strain could be clearly distinguished from the related species of the genus Paraliobacillus by its phylogenetic position and biochemical characteristics. It presented MK-7 as the major quinone and the dominant cellular fatty acids were iso-C16 : 0, anteiso-C15 : 0, C16 : 0 and iso-C14 : 0. The polar lipids consisted of diphosphatidylglycerol and phosphatidylglycerol as the major components. The G+C content of strain G6-18T genome was 35.3 mol%. 16S rRNA analysis showed that strain G6-18T had the highest similarity to Paraliobacillus ryukyuensis DSM 15140T, reaching 97.0 %, followed by Paraliobacillus quinghaiensis CGMCC 1.6333T with a value of 96.3 %. The average nucleotide identity values between strain G6-18T and Paraliobacillus ryukyuensis DSM 15140T, Paraliobacillus sedimins KCTC 33762T, Paraliobacillus quinghaiensis CGMCC 1.6333T and Paraliobacillus zengyii DSM 107811T were 74.3, 72.0, 73.2 and 72.8 %, respectively, and the digital DNA-DNA hybridization values between strain G6-18T and the neighbouring strains were 15.6, 13.8, 14.2 and 14.2 %, respectively. Based on phenotypic, chemotaxonomic and phylogenetic inferences, strain G6-18T represents a novel species of the genus Paraliobacillus, for which the name Paraliobacillus salinarum sp. nov. (=CGMCC 1.12058T=DSM 25428T) is proposed.

Siccirubricoccus phaeus sp. nov., isolated from oil reservoir water and emended description of the genus Siccirubricoccus.

A Gram-staining-negative, non-motile, aerobic bacterium, designated 1-3T, was isolated from oil reservoir water collected from Liaohe oilfield, north-east of China. Growth was observed at 15-40 °C (optimum 37 °C) and pH 6-10 (optimum 7). The strain can grow under nitrogen-limiting condition. Phylogenetic analysis based on 16S rRNA gene sequences showed that the novel isolate was most closely related to Siccirubricoccus deserti SYSU D8009T (96.7%), followed by Paracraurococcus ruber NS89T (95.7%) and Belnapia rosea CPCC 100156T (94.9%). Genome sequencing revealed a genome size of 6.43 Mbp and a G+C content of 71.3 mol%. The average nucleotide identity values and digital DNA-DNA hybridization between 1-3T and the reference strains were all below the cut-off level (95-96% and 70%, respectively) for species delineation. The strain possessed the cytochrome P450 enzyme, which has the potential to degrade oil. The respiratory quinone was Q-10 and the major fatty acids were summed feature 8 (C18:1 ω7c/C18:1 ω6c, 38.8%), C16:0 (25.6%) and C19:0 cyclo ω8c (22.5%). The polar lipids of strain 1-3T comprised diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine and three unidentified aminolipids. Based on the genotypic and phenotypic characteristics, strain 1-3T represents a novel species of genus Siccirubricoccus, for which the name Siccirubricoccus phaeus sp. nov. is proposed. The type strain of Siccirubricoccus phaeus is 1-3T (= CGMCC 1.16799T = LMG 31398T).

Paracoccus alkanivorans sp. nov., isolated from a deep well with oil reservoir water.

A Gram-stain-negative, non-motile and ovoid bacterial strain, designated 4-2T, was isolated from oil-contaminated water which was collected from Xinjiang Province, north-west PR China. The 16S rRNA gene sequence analysis showed that strain 4-2T belonged to the genus Paracoccus. The species with highest similarity to strain 4-2T was Paracoccus saliphilus YIM 90738T (97.83 %), followed by 'Paracoccus siganidrum' M26 (97.83 %) and Paracoccus endophyticus SYSUP0003T (97.25 %). The average nucleotide identity values between 4-2T and three type strains were 84.69, 77.88 and 74.07 %, respectively. The genomic DNA G+C content of strain 4-2T was 61.4 mol%. Chemotaxonomical characteristic results showed that the respiratory quinone was ubiquinone Q-10 and the major fatty acids were summed feature 8 (C18 : 1 ω7c or C18 : 1 ω6c) and C19 : 0 cyclo ω8c. The polar lipid profile consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, unidentified phospholipids, an unidentified aminolipid and an unidentified polar lipid. The predominant polyamines were putrescine, cadaverine and spermidine. On the basis of phenotypic, chemotaxonomic and phylogenetic inferences, strain 4-2T represents a novel species of the genus Paracoccus, for which the name Paracoccus alkanivorans sp. nov. is proposed. The type strain is 4-2T (=CGMCC 1.13669T=LMG 30882T).

Frigidibacter oleivorans sp. nov., isolated from a deep well with oil reservoir water.

A Gram-stain-negative, rod-shaped bacterium, designated XJ4T, was isolated from oil-contaminated water, collected from Xinjiang Province, north-west PR China (45° 1' 27″ N, 85° 6' 14″ E). Growth occurred at 20-45 °C (optimum, 30 °C) and pH 6.0-10.0 (optimum, pH 6.0-7.0). Strain XJ4T could tolerate up to 7 % (w/v) NaCl and grow optimally in the absence of NaCl. Phylogenetic analysis based on comparative sequence analysis of 16S rRNA gene sequences indicated that strain XJ4T belonged to the genus Frigidibacter, and that was closely related to Frigidibacter mobilis cai42T (97.2 %), Frigidibacter albus SP32T (97.0 %) and Rhodobacter aestuarii JA296T (97.0 %). The average nucleotide identity values between XJ4T and three type strains were 77.9, 77.6 and 71.9 %, respectively. The DNA G+C content of strain XJ4T was 69.5 mol%. The sole respiratory quinone was Q-10. The major cellular fatty acid was summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c), C18 : 0 and 11-methyl C18 : 1 ω7c. The polar lipids were diphosphatidylglycerol, phosphatidylglycerol, unidentified phospholipids, an unidentified aminolipid and unidentified lipids. On the basis of phenotypic, chemotaxonomic and phylogenetic analyses, strain XJ4T represents a novel species of the genus Frigidibacter, for which the name Frigidibacter oleivorans sp. nov. is proposed. The type strain is XJ4T (=CGMCC 1.13778T=LMG 30952T).

Oleiliquidispirillum nitrogeniifigens gen. nov., sp. nov., a new member of the family Rhodospirillaceae isolated from oil reservoir water.

A novel Gram-staining-negative, spiral-shaped bacterium, designated strain 64-1T, was isolated from oil reservoir water collected from Liaohe oilfield, north-eastern China. Growth occurred at 15-55 °C and pH 6.0-10.0. The sole respiratory quinone was Q-10. The predominant cellular fatty acids were summed feature 8 (C18 : 1 ω7c /C18 : 1 ω6c), C16 : 0 and C19 : 0 cyclo ω8c. The polar lipids consisted of phosphatidylethanolamine (PE), phosphatidylglycerol (PG), phosphatidylcholine (PC), an unidentified aminophospholipid (UAPL), an unidentified aminolipid (UAL) and two unidentified polar lipids (UPL). The genomic DNA G+C content of strain 64-1T was 64.5 mol%. Strain 64-1T shared the highest 16S rRNA gene sequence similarities with Phaeospirillum chandramohanii JA145T (92.0 %) and Telmatospirillum siberiense 26-4b1T (91.8 %). In the phylogenetic trees, the strain constituted a sub-cluster within the family Rhodospirillaceae. Based on the results of morphological, physiological, biochemical and phylogenetic analysis, strain 64-1T represents a new species of a novel genus within the family Rhodospirillaceae, for which the name Oleiliquidispirillum nitrogeniifigens gen. nov., sp. nov. is proposed. The type strain is 64-1T (=CGMCC 1.16798T=LMG 31399T).

Human T-cell leukemia virus type 1 Tax-deregulated autophagy pathway and c-FLIP expression contribute to resistance against death receptor-mediated apoptosis.

UNLABELLED: The human T-cell leukemia virus type 1 (HTLV-1) Tax protein is considered to play a central role in the process that leads to adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-1 Tax-expressing cells show resistance to apoptosis induced by Fas ligand (FasL) and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL). The regulation of Tax on the autophagy pathway in HeLa cells and peripheral T cells was recently reported, but the function and underlying molecular mechanism of the Tax-regulated autophagy are not yet well defined. Here, we report that HTLV-1 Tax deregulates the autophagy pathway, which plays a protective role during the death receptor (DR)-mediated apoptosis of human U251 astroglioma cells. The cellular FLICE-inhibitory protein (c-FLIP), which is upregulated by Tax, also contributes to the resistance against DR-mediated apoptosis. Both Tax-induced autophagy and Tax-induced c-FLIP expression require Tax-induced activation of IκB kinases (IKK). Furthermore, Tax-induced c-FLIP expression is regulated through the Tax-IKK-NF-κB signaling pathway, whereas Tax-triggered autophagy depends on the activation of IKK but not the activation of NF-κB. In addition, DR-mediated apoptosis is correlated with the degradation of Tax, which can be facilitated by the inhibitors of autophagy. IMPORTANCE: Our study reveals that Tax-deregulated autophagy is a protective mechanism for DR-mediated apoptosis. The molecular mechanism of Tax-induced autophagy is also illuminated, which is different from Tax-increased c-FLIP. Tax can be degraded via manipulation of autophagy and TRAIL-induced apoptosis. These results outline a complex regulatory network between and among apoptosis, autophagy, and Tax and also present evidence that autophagy represents a new possible target for therapeutic intervention for the HTVL-1 related diseases.

Opposing Effects of Nutritional Supply on Bone Health at Different Ages: Based on the National Health and Nutrition Examination Survey Database.

(1) Background: Nutrients play an essential role in bone health, whether in achieving peak bone mineral density (BMD) or maintaining bone health. This study explores the relationship between nutrient supply and femoral bone health at different ages. (2) Methods: A total of 5603 participants meeting the inclusion and exclusion criteria were included in this study using the National Health and Nutrition Examination Survey (NHANES) database from 2005 to 2010, 2013 to 2014, and 2017 to 2018. Femoral bone mineral density and bone status were dependent variables, and dietary nutrient intake and nutrient intake status were independent variables. The relationship between dietary nutrient intake and bone mineral density was explored, and the importance of nutrients affecting bone status was analyzed through a neural network model. At the same time, we investigated the relationship between nutrient intake and bone status. (3) Results: The peak of age and femoral bone mineral density appeared at 20 years old in our study. After grouping by age, logistic regression analysis showed that before 20 years old, without adjusting other variables, high-fat diet was more likely to have normal bone mass than appropriate fat diet (OR: 4.173, 95%CI: 1.007-17.289). After adjusting for all demographic factors, niacin intake (OR: 1.062, 95%CI: 1.019-1.108) was beneficial for normal bone mass, while vitamin B6 intake (OR: 0.627, 95%CI: 0.408-0.965) was not. After 20 years old, after adjusting for carbohydrate, protein, vitamin B6, niacin, dietary fat, vitamin B2, and vitamin B12, vitamin B2 intake (OR: 1.153, 95%CI: 1.04-1.278) was beneficial for normal bone mass, while vitamin B6 intake (OR: 0.842, 95%CI: 0.726-0.976) was not. After adjusting for all confounding factors, vitamin B2 intake (OR: 1.288, 95%CI: 1.102-1.506) was beneficial for normal bone mass. In addition, we found that even if there was no statistical significance, the effects of high-fat diet on bone mass were different at different ages. (4) Conclusions: By conducting an in-depth analysis of the NHANES database, this study reveals that dietary factors exert divergent effects on bone health across different age groups, implying the necessity of implementing tailored dietary strategies to maintain optimal bone health at distinct life stages.

Folic acid supplementation prevents high body fat-induced bone loss through TGR5 signaling pathways.

Osteoporosis caused by bone loss is one of the serious global public health problems. Folic acid is a B vitamin with multiple physiological functions such as lipid regulation and antioxidant capacity, and its potential to improve bone loss has attracted our attention. Through NHANES database analysis, we found that folic acid intake was significantly correlated with whole-body bone mineral density (BMD) in people aged 20-60 years, and the association may be mediated by the body fat rate. Male C57Bl/6 mice were fed either a normal diet or a high-fat diet, and folic acid was added to drinking water for supplementation. Our results indicated that mice with high body fat showed bone microstructure damage and bone loss, while folic acid supplementation improved bone quality. At the same time, we found that mice with high body fat exhibited abnormal blood lipids, dysregulation of intestinal flora, and metabolic disorders. Folic acid supplementation improved these phenomena. Through the network analysis of intestinal flora and metabolites, we found that LCA and TGR5 may play important roles. The results showed that folic acid promoted the expression of LCA and TGR5 in mice, increased the phosphorylation of AMPK, and decreased the phosphorylation of NF-κB and ERK, thereby reducing bone loss. In summary, folic acid intake is closely related to BMD, and folic acid supplementation can prevent high body fat-induced bone loss. Our study provides new ideas and an experimental basis for preventing bone loss and osteoporosis.

Enhanced Electromagnetic Interference Shielding Properties of CNT/Carbon Composites by Designing a Hierarchical Porous Structure.

With the widespread use of electronic devices, electromagnetic interference (EMI) has become an increasingly severe issue, adversely affecting device performance and human health. Carbon nanotubes (CNTs) are recognized for their electrical conductivity, flexibility, and stability, making them promising candidates for EMI shielding applications. This research developed hierarchical porous-structured CNT/carbon composites for enhancing electromagnetic interference (EMI) shielding properties. Featuring a CNT film with nano-scale pores and an amorphous carbon layer with micro-scale pores, the CNT/carbon composites are strategically arranged to promote the penetration of EM waves into the composite's interior and facilitate multiple reflections, thereby improving the EMI shielding performance. An impressive EMI shielding effectiveness of 61.4 dB was achieved by the CNT/carbon composites, marking a significant improvement over the 36.5 dB measured for the pristine CNT film. Owing to the micro pores in the amorphous carbon layer, a notable reduction in the reflection shielding efficiency (SER) but, concurrently, a substantial increase in the absorption shielding efficiency (SEA) compared with the pristine CNT film was realized in the composites. This study successfully validated the effectiveness of the hierarchical porous structure in enhancing the EMI shielding performance, providing a promising new strategy for the development of lightweight, flexible, and efficient EMI shielding materials.

The ankyrin-repeat transmembrane protein BDA1 functions downstream of the receptor-like protein SNC2 to regulate plant immunity.

Plants utilize a large number of immune receptors to recognize pathogens and activate defense responses. A small number of these receptors belong to the receptor-like protein family. Previously, we showed that a gain-of-function mutation in the receptor-like protein SNC2 (for Suppressor of NPR1, Constitutive2) leads to constitutive activation of defense responses in snc2-1D mutant plants. To identify defense signaling components downstream of SNC2, we carried out a suppressor screen in the snc2-1D mutant background of Arabidopsis (Arabidopsis thaliana). Map-based cloning of one of the suppressor genes, BDA1 (for bian da; "becoming big" in Chinese), showed that it encodes a protein with amino-terminal ankyrin repeats and carboxyl-terminal transmembrane domains. Loss-of-function mutations in BDA1 suppress the dwarf morphology and constitutive defense responses in snc2-1D npr1-1 (for nonexpressor of pathogenesis-related genes1,1) and also result in enhanced susceptibility to bacterial pathogens. In contrast, a gain-of-function allele of bda1 isolated from a separate genetic screen to search for mutants with enhanced pathogen resistance was found to constitutively activate cell death and defense responses. These data suggest that BDA1 is a critical signaling component that functions downstream of SNC2 to regulate plant immunity.

Arabidopsis snc2-1D activates receptor-like protein-mediated immunity transduced through WRKY70.

Plant immune receptors belonging to the receptor-like protein (RLP) family contain extracellular leucine-rich repeats (LRRs) and a short cytoplasmic tail linked by a single transmembrane motif. Here, we report the identification of snc2-1D (for suppressor of npr1-1, constitutive 2), a semidominant Arabidopsis thaliana mutant with constitutively activated defense responses. Map-based cloning of snc2-1D showed that it encodes an RLP. The point mutation in snc2-1D leads to substitution of the second Gly for Arg in the conserved GXXXG motif of the transmembrane helix, suggesting that this residue is important for negative regulation of the protein. Epistasis analysis revealed that the snc2-1D mutant phenotype is not affected by mutations in genes known to be required for the nucleotide binding (NB)-LRR Resistance (R) protein signaling. A suppressor screen of snc2-1D was performed, and map-based cloning of one suppressor revealed that mutations in WRKY70 suppress the constitutive defense responses in snc2-1D, suggesting that WRKY70 functions downstream of snc2-1D. The identification of snc2-1D provides us with a unique system for genetic analysis of resistance pathways downstream of RLPs, which may be distinct from those downstream of NB-LRR type R proteins.

Arabidopsis resistance protein SNC1 activates immune responses through association with a transcriptional corepressor.

In both plants and animals, nucleotide-binding (NB) domain and leucine-rich repeat (LRR)-containing proteins (NLR) function as sensors of pathogen-derived molecules and trigger immune responses. Although NLR resistance (R) proteins were first reported as plant immune receptors more than 15 years ago, how these proteins activate downstream defense responses is still unclear. Here we report that the Toll-like/interleukin-1 receptor (TIR)-NB-LRR R protein, suppressor of npr1-1, constitutive 1 (SNC1) functions through its associated protein, Topless-related 1 (TPR1). Knocking out TPR1 and its close homologs compromises immunity mediated by SNC1 and several other TIR-NB-LRR-type R proteins, whereas overexpression of TPR1 constitutively activates SNC1-mediated immune responses. TPR1 functions as a transcriptional corepressor and associates with histone deacetylase 19 in vivo. Among the target genes of TPR1 are Defense no Death 1 (DND1) and Defense no Death 2 (DND2), two known negative regulators of immunity that are repressed during pathogen infection, suggesting that TPR1 activates R protein-mediated immune responses through repression of negative regulators.