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Though the terahertz fingerprint spectroscopy enables the fast and unique detection and identification of organic or bio-molecules, it remains a challenge to acquire broad terahertz absorption spectra of trace-mount samples. In this paper, a strategy is proposed to boost terahertz absorption spectroscopy of organic film on a stretchable metasurface. The metasurface substrate and unit cell structures are constructed using polydimethylsiloxane (PDMS) material. The resonance peak frequency of the metasurface absorption corresponding to different stretching factors can cover the frequency range of 0.48–0.58 THz. When the metasurface surface is covered with a 0.2 μm thickness α-lactose film, the envelop absorption formed by the peak values of the metasurface absorption spectrum, with stretching factors ranging from 100% to 124%, can significantly enhance the absorption of the same thickness film by over 101 times. The investigation results demonstrate that the stretchable metasurface can obviously strengthen the terahertz absorption of the tiny sample. By optimizing the unit cell design of the metasurface, it may be possible to identify other small volume organic compounds with diverse characteristic peaks. [ABSTRACT FROM AUTHOR]

Perioperative neurocognitive disorders (PNDs) are some of the most common postoperative complications among the elderly and susceptible individuals, which significantly worsens the clinical outcome of patients. However, the prevention and treatment strategies of PNDs are difficult to determine and implement since the pathogenesis of PNDs is not well understood. The development of living organisms is associated with active and organized cell death, which is essential for maintaining the homeostasis of life. Ferroptosis is a programmed cell death (different from apoptosis and necrosis) mainly caused by an imbalance in the generation and degradation of intracellular lipid peroxides due to iron overload. Pyroptosis is an inflammatory cell death characterized by the creation of membrane holes mediated by the gasdermin (GSDM) family, followed by cell lysis and the release of pro-inflammatory cytokines. Ferroptosis and pyroptosis are involved in the pathogenesis of various central nervous system (CNS) diseases. Furthermore, ferroptosis and pyroptosis are closely associated with the occurrence and development of PNDs. This review summarizes the main regulatory mechanisms of ferroptosis and pyroptosis and the latest related to PNDs. Based on the available evidence, potential intervention strategies that can alleviate PNDs by inhibiting ferroptosis and pyroptosis have also been provided. [ABSTRACT FROM AUTHOR]

Objectives: Net water uptake (NWU) has been shown to have a linear relationship with brain edema. Based on an automated-Alberta Stroke Program Early Computed Tomography Score (ASPECTS) technique, we automatically derived NWU from baseline multimodal computed tomography (CT), namely ASPECTS-NWU. We aimed to determine if ASPECTS-NWU can predict the development of malignant cerebral edema (MCE). Methods: One hundred and forty-six patients with large-vessel occlusion were retrospectively enrolled. Quantitative NWU based on automated-ASPECTS was measured both on nonenhanced CT (NECT) and CT angiography (CTA), namely NECT-ASPECT-NWU and CTA-ASPECTS-NWU. The correlation between ASPECTS-NWU and cerebral edema (CED) grades was calculated using Spearman rank correlation. Univariate logistic regression was used to assess the effect of radiological and clinical features on MCE, and a multivariable model with significant factors from the univariate regression analysis was built. Receiver operating characteristic (ROC) was obtained and area under curve (AUC) was compared. Results: CTA-ASPECTS-NWU had a moderate positive correlation with CED grades (r = 0.62; 95% confidence interval [CI], 0.51–0.71; p < 0.001). The CTA-ASPECTS-NWU performed better than the NECT-ASPECTS-NWU with AUC: 0.88 vs. 0.71 (p < 0.001). Multivariable logistic regression model integrating CTA-ASPECTS-NWU, collateral score, and age showed the CTA-ASPECTS-NWU was an independent predictor of MCE with an AUC of 0.94 (95% CI: 0.90–0.98; p < 0.001). Conclusions: This study demonstrates that ASPECTS-NWU is a quantitative predictor of MCE after large-vessel occlusion of the middle cerebral artery territory. The multivariable logistic regression model may enhance the identification of patients with MCE needing anti-edematous treatment. Key Points: • The automated-ASPECTS technique can automatically detect the affected regions with early ischemic changes and NWU could be manually calculated. • The CTA-ASPECTS-NWU performs better than the NECT-ASPECTS-NWU on predicting the development of MCE. • The multivariable logistic regression model may enhance the identification of patients with MCE needing anti-edematous treatment. [ABSTRACT FROM AUTHOR]

To address the current data and understanding knowledge gap in landslide dam inventories related to geomorphological parameters, a new global-scale landslide dam dataset named River Augmented Global Landslide Dams (RAGLAD) was created. RAGLAD is a collection of landslide dam records from multiple data sources published in various languages and many of these records we have been able to precisely geolocate. In total, 779 landslide dam records were compiled from 34 countries/regions. The spatial distribution, time trend, triggers, and geomorphological characteristic of the landslides and catchments where landslide dams formed are summarized. The relationships between geomorphological characteristics for landslides that form river dams are discussed and compared with those of landslides more generally. Additionally, a potential threshold for landslide dam formation is proposed, based on the relationship of landslide volume to river width. Our findings from our analysis of the value of the use of additional fluvial datasets to augment the database parameters indicate that they can be applied as a reliable supplemental data source, when the landslide dam records were accurately and precisely geolocated, although location precision in smaller river catchment areas can result in some uncertainty at this scale. This newly collected and supplemented dataset will allow the analysis and development of new relationships between landslides located near rivers and their actual propensity to block those particular rivers based on their geomorphology. [ABSTRACT FROM AUTHOR]

Point cloud completion aims to restore full shapes of objects from their partial views obtained by 3D optical scanners. In order to make point cloud completion become more robust to azimuthal rotations and more adaptive to real-world scenarios, we propose a novel network for simultaneous rotation invariant and equivariant completion with no need of data augmentation, while other existing approaches require separately trained models for different completion types. Our method includes several main steps: First, Density Compensation Mapping (DCM) as well as Aggregative Gaussian Gridding (AGG) modules are introduced to transfer partial point clouds to spherical signals and avoid unbalanced sampling. Second, an encoder based on group correlation is designed to extract rotation invariant global features and equivariant azimuthal features from spherical signals. Third, parallel groups of decoders are proposed to realize rotation invariant completion based on feature fusion. Finally, a feature remapping module as well as Pose Voting Alignment (PVA) algorithm are proposed to unify feature space and realize rotation equivariant completion. Based on these modules, we find that the application of group correlation can be extended to the domain of shape completion; equivariant and invariant completions can be unified in one pipeline, and our inherent rotation equivariant and invariant framework can achieve competitive performances when comparing with existing representative methods. [ABSTRACT FROM AUTHOR]

Objective: We assessed the value of computed tomography (CT) and automated Alberta Stroke Program Early CT Score (ASPECTS) with net water uptake (NWU) to predict stroke onset time. Methods: Two-hundred forty stroke patients with anterior circulation large-vessel occlusion were included. CT-ASPECTS-NWU values were calculated by comparing the mean Hounsfield units of affected ASPECTS regions with unaffected contralateral regions. The correlation between ASPECTS-NWU and stroke onset to CT time was assessed. ASPECTS-NWU predictive values were calculated to identify a stroke onset to CT time of within 4.5/6 h. Results: A correlation existed between stroke onset to CT time and ASPECTS-NWU (r = 0.65, p < 0.001), which was affected by collateral status and infarct location. The area under the receiver operating characteristic (ROC) curve (AUC) for distinguishing a stroke onset to CT time of within 4.5 h was 0.837 (95% confidence interval [CI] 0.784–0.881; optimal cutoff 7%; sensitivity 87.10%; specificity 62.36%). The multi-index AUC was 0.884 (95% CI 0.837–0.922). The AUC for distinguishing a stroke onset to CT time of within 6 h was 0.836 (95% CI 0.783–0.880; optimal cutoff 9%; sensitivity 72.73%; specificity 81.16%). The multi-index AUC was 0.881 (95% CI 0.834–0.920). Conclusions: ASPECTS-NWU may be used to determine stroke onset time in patients with unwitnessed or wake-up stroke. [ABSTRACT FROM AUTHOR]

The histogram of oriented gradients (HOG) is widely used for image description and has proven to be very effective. In some practical applications that lack an assumption of the object’s orientation, rotation-invariant detection is of vital significance. To address this problem, this paper presents a new visual feature, Sector-ring HOG (SRHOG), which is obtained by improving the gradient binning and spatial binning based on HOG. The new feature can convert planar image rotations into cyclic shifts of the final descriptor and thereby facilitate rotated object detection. After modifying boosted random ferns in SRHOG feature domain, we further propose two strategies for rotation-invariant object detection: one depends completely on the new feature’s characteristic, and the other introduces an orientation estimation step. The former is more suitable to ‘finding objects’ and the latter can provide the higher orientation estimation accuracy. Both the use of supervised learning and working in the gradient space make our approaches effective and robust. We show these properties by thorough testing on the public Freestyle Motocross dataset and our dataset for victim detection in post-disaster rescue efforts. [ABSTRACT FROM AUTHOR]

Maleic anhydride grafted polypropylene (PP-g-MAH) is an effective compatibilizer in the preparation of polypropylene composites. Its grafting ratio plays an important role in the dispersion of filler or blend in polypropylene (PP) matrix resin, but the grafting ratio of PP-g-MAH prepared by reactive extrusion is low. A method for preparing PP-g-MAH with high grafting ratio and low odor was proposed by combining microwave reaction and melt extrusion. The grafting ratio of the PP-g-MAH products obtained by this method without the assistance of comonomer reached 1.95%. The results of melt index and rheology showed that the crosslinking occurred during the preparation process, thus avoiding the large reduction of molecular weight of PP. Meanwhile, the problem of odor was avoided because no comonomer was added during the process. The application results showed that PP-g-MAH prepared by this method improves the compatibility of glass fiber (GF) and PP, thus improving the mechanical properties of polypropylene/glass fiber (PP/GF) composites. This work explored a novel way to prepare PP-g-MAH with high grafting ratio. [ABSTRACT FROM AUTHOR]

Nitrate is necessary for primary and secondary metabolism of actinomycetes and stimulates the production of a few antibiotics, such as lincomycin and rifamycin. However, the mechanism of this nitrate-stimulating effect was not fully understood. Two putative ABC-type nitrate transporters were identified in Streptomyces lincolnensis NRRL2936 and verified to be involved in lincomycin biosynthesis. With nitrate supplementation, the transcription of nitrogen assimilation genes, nitrate-specific ABC1 transporter genes, and lincomycin exporter gene lmrA was found to be enhanced and positively regulated by the global regulator GlnR, whose expression was also improved. Moreover, heterologous expression of ABC2 transporter genes in Streptomyces coelicolor M145 resulted in an increased actinorhodin production. Further incorporation of a nitrite-specific transporter gene nirC, as in nirC-ABC2 cassette, led to an even higher actinorhodin production. Similarly, the titers of salinomycin, ansamitocin, lincomycin, and geldanamycin were increased with the integration of this cassette to Streptomyces albus BK3-25, Actinosynnema pretiosum ATCC31280, S. lincolnensis LC-G, and Streptomyces hygroscopicus XM201, respectively. Our work expanded the nitrate-stimulating effect to many antibiotic producers by utilizing the nirC- ABC2 cassette for enhanced nitrate utilization, which could become a general tool for titer increase of antibiotics in actinomycetes. [ABSTRACT FROM AUTHOR]

Giant linear plasmids, which replicate independently of the chromosomes, widely exist in actinobacteria. Previous studies mostly focused on the replication and evolution of the linear plasmids or the secondary metabolite gene clusters and the resistance gene clusters therein. However, the relationships of the linear plasmids to the productivities of secondary metabolites have not been studied. In this work, we developed a method to eliminate the indigenous linear plasmid pSHJG1 in Streptomyces hygroscopicus var. jinggangensis, and validamycin A titer increased by 12.5% (from 19.16 ± 1.93 to 21.56 ± 2.25 g/L) in the high-yielding strain TL01 and 43.7% (from 4.67 ± 0.05 to 6.71 ± 0.21 g/L) in the wild-type strain 5008, whereas the cellular growth of the plasmid-cured mutant was reduced. Subsequently, the plasmid-cured mutant was complemented with three structure genes involved in cellular growth in pSHJG1 under the control of a strong PvalA promoter. Among them, the complementation of genes pSHJG1.069 and pSHJG1.072, encoding a putative hydrolase and putative P-loop ATPase, respectively, resulted in the restoration of cellular growth and validamycin A titer. Furthermore, the elimination of indigenous linear plasmid pHZ228 in the candicidin producer Streptomyces sp. FR008 also led to enhanced candicidin production and reduced cellular growth. Because of the wide distribution of indigenous linear plasmids in actinobacteria, the engineering strategy described here could be implemented in a variety of strains for the overproduction of various natural products. [ABSTRACT FROM AUTHOR]

Glycosyltransferase DesVII and its auxiliary partner DesVIII from Streptomyces venezulae, homologs of EryCIII and EryCII in Saccharopolyspora erythraea, have previously been demonstrated to be flexible on their substrates in vitro. Herein, we investigated their in vivo function by interspecies complementation in the mutant strains of Sac. erythraea A226. As desVII and desVIII were concomitantly expressed in the Δ eryCIII mutant, the erythromycin A (Er-A) production was restored. Interestingly, co-expression of desVII and desVIII in the Δ eryBV mutant exhibited an increased Er-A yield by 15 % in comparison to A226. Hence, DesVII/DesVIII not only replaced EryCIII to upload D-desosamine to C5 position of 3-O-mycarosyl erythronolide B (MEB) but also in vivo attached L-mycarose, not D-desosamine to C3 position of erythronolide B (EB) with a higher activity than EryBV. Furthermore, expression of desVII in Δ eryCIII and Δ eryBV-CIII partially restored the Er-A production; however, no Er-A was detected while desVII was expressed in Δ eryBV. It was implicated that DesVII coupled with EryCII to form the DesVII/EryCII complex for attaching above two deoxysugars in the absence of EryCIII in Sac. erythraea. In addition, when desVII and desVIII were co-expressed in Δ eryBV-CII, Er-A was recovered with a lower yield than Δ eryBV-CIII. Our study presents an opportunity with Sac. erythraea as a cell factory for macrolide glycodiversification. [ABSTRACT FROM AUTHOR]

BldD (SACE_2077), a key developmental regulator in actinomycetes, is the first identified transcriptional factor in Saccharopolyspora erythraea positively regulating erythromycin production and morphological differentiation. Although the BldD of S. erythraea binds to the promoters of erythromycin biosynthetic genes, the interaction affinities are relatively low, implying the existence of its other target genes in S. erythraea. Through the genomic systematic evolution of ligands by exponential enrichment (SELEX) method that we herein improved, four DNA sequences of S. erythraea A226, corresponding to the promoter regions of SACE_0306 (beta-galactosidase), SACE_0811 (50S ribosomal protein L25), SACE_3410 (fumarylacetoacetate hydrolase), and SACE_6014 (aldehyde dehydrogenase), were captured with all three BldD concentrations of 0.5, 1, and 2 μM, while the previously identified intergenic regions of eryBIV-eryAI and ermE-eryCI plus the promoter region of SACE_7115, the amfC homolog for aerial mycelium formation, could be captured only when the BldD's concentration reached 2 μM. Electrophoretic mobility shift assay (EMSA) analysis indicated that BldD specifically bound to above seven DNA sequences, and quantitative real-time PCR (qRT-PCR) assay showed that the transcriptional levels of the abovementioned target genes decreased when bldD was disrupted in A226. Furthermore, SACE_7115 and SACE_0306 in A226 were individually inactivated, showing that SACE_7115 was predominantly involved in aerial mycelium formation, while SACE_0306 mainly controlled erythromycin production. This study provides valuable information for better understanding of the pleiotropic regulator BldD in S. erythraea, and the improved method may be useful for uncovering regulatory networks of other transcriptional factors. [ABSTRACT FROM AUTHOR]

Malignant tumor has always been a complex disease that endangers human health. Traditional treatment methods include surgical resection, chemotherapy, and radiotherapy. However, solid tumors are prone to recur. Herein, we developed a hydrogel-based drug-carrying system to prevent postoperative tumor recurrence. Sodium carboxymethyl cellulose was modified with dopamine via the N-hydroxysuccinimide (NHS) and 1-ethyl-(3-dimethylaminopropyl) carbanyl diimide (EDC)-mediated coupling chemistry. The CMC-DA-MnO2/MnO (CDM) hydrogel was prepared by oxidative cross-linking, using KMnO4 as the oxidizing agent. In the hydrogel, the KMnO4 can not only be used as an oxidant to trigger the polymerization and gelation of CMC-DA but also transformed into MnO2 and MnO to afford the T2-weighted magnetic resonance imaging (MRI). The fluorescent dye IR808 as a photosensitizer was introduced into the hydrogel system by simply soaking the CDM hydrogel in the IR808 solution. Under the 808 nm laser irradiation, IR808 and PDA endowed the hydrogel with tumor photodynamic therapy (PDT) and photothermal therapy (PTT) capacities, respectively. With the proven hemo- and cyto-compatibilities, the CDM hydrogel was successfully used for the PDT and PTT prevention of postoperative tumor recurrence. [ABSTRACT FROM AUTHOR]

Let { Y, Y i , −∞ < i < ∞} be a doubly infinite sequence of identically distributed and asymptotically linear negative quadrant dependence random variables, { a i , −∞ < i < ∞} an absolutely summable sequence of real numbers. We are inspired by Wang et al. (Econometric Theory 18:119–139, ) and Salvadori (Stoch Environ Res Risk Assess 17:116–140, ). And Salvadori (Stoch Environ Res Risk Assess 17:116–140, ) have obtained Linear combinations of order statistics to estimate the quantiles of generalized pareto and extreme values distributions. In this paper, we prove the complete convergence of $${\left\{ {{\sum\nolimits_{k = 1}^n {{\sum\nolimits_{i = - \infty }^\infty {a_{{i + k}} Y_{i} /n^{{1/t}} } }} },n \geq 1} \right\}}$$ under some suitable conditions. The results obtained improve and generalize the results of Li et al. () and Zhang (). The results obtained extend those for negative associated sequences and ρ*-mixing sequences. [ABSTRACT FROM AUTHOR]

CT densitometry-based methods to directly quantify net water uptake in ischemic brain tissue have been increasingly applied recently. There is potential for net water uptake to be used as an imaging biomarker for the pathophysiology of infarcted lesions. This review is aimed at summarizing the potential and current status of the application of net water uptake as a biomarker in the management of ischemic stroke and future directions in this context. Specifically, we provide a brief overview of the principle and different methods of net water uptake measurement, followed by a discussion of the role of net water uptake in predicting malignant brain edema and hemorrhagic transformation, evaluating lesion age, and predicting the efficacy of reperfusion therapy and long-term clinical prognosis. Artificial intelligence will help address the lack of automation and standardization in the measurement of net water absorption. Further validation of net water uptake in a prospective multicenter setting is necessary. Key Points: • NWU can be used as a quantitative imaging biomarker for developing malignant brain edema in anterior and posterior circulation strokes. • The difference in NWU in edema arrest or reversibility suggests that rapid and successful revascularization can influence the progression of ischemic edema. • NWU can be used to predict the age of a lesion, with predictive power comparable to that of DWI/FLAIR mismatch. [ABSTRACT FROM AUTHOR]

This study aimed to determine the role of IFN-1 gene signatures in SLE and their association with Sjögren syndrome (SS). Publicly available data from the Gene Expression Omnibus database were used to construct the models. The random forest tree model was used to screen key IFN-1 gene signatures, and consensus clustering algorithms were used for unsupervised cluster analysis of these signatures. CIBERSORT and gene set variation analyses were used to evaluate the relative immune cell infiltration and enriched molecular pathways of the samples, respectively. Weighted gene co-expression network analysis was used to identify the co-expression modules and hub genes. Finally, univariate and multivariate logistic regression models were used to evaluate differences in clinical and laboratory characteristics between the different groups. The role of IFN-1 gene signatures in SLE was comprehensively assessed, which revealed an IFN-1 gene signature including six genes that could easily distinguish SLE patients and healthy individuals and identified two distinct IFN-1 subtypes exhibiting significant differences in clinical characteristics, immune microenvironment, and biological functional pathways. The SLE disease activity index, lower lymphocyte count, nucleotide oligomerization domain (NOD)-like receptor signaling pathway, and dendritic cell activation were strongly correlated with the IFN-1 gene signatures. In addition, we found that IFN-1 gene signatures in SLE may be an important susceptibility factor for SS, and the NOD-like receptor signaling pathway was identified as a common pathway. This study provides a comprehensive evaluation of the IFN-1 gene signatures, which may provide a new direction for the understanding of SLE and SS and help in the selection of optimal strategies for personalized immunotherapy. [ABSTRACT FROM AUTHOR]

TetR family transcriptional regulators (TFRs) are widespread in actinomycetes, which exhibit diverse regulatory modes in antibiotic biosynthesis. Nitrogen regulators play vital roles in modulation of primary and secondary metabolism. However, crosstalk between TFR and nitrogen regulator has rarely been reported in actinomycetes. Herein, we demonstrated that a novel TFR, SACE_4839, was negatively correlated with erythromycin yield in Saccharopolyspora erythraea A226. SACE_4839 indirectly suppressed erythromycin synthetic gene eryAI and resistance gene ermE and directly inhibited its adjacent gene SACE_4838 encoding a homologue of nitrogen metabolite repression (NMR) regulator NmrA (herein named NmrR). The SACE_4839-binding sites within SACE_4839-nmrR intergenic region were identified. NmrR positively controlled erythromycin biosynthesis by indirectly stimulating eryAI and ermE and directly repressing SACE_4839. NmrR was found to affect growth viability under the nitrogen source supply. Furthermore, NmrR directly repressed glutamine and glutamate utilization-related genes SACE_1623, SACE_5070 and SACE_5979 but activated nitrate utilization-associated genes SACE_1163, SACE_4070 and SACE_4912 as well as nitrite utilization-associated genes SACE_1476 and SACE_4514. This is the first reported NmrA homolog for modulating antibiotic biosynthesis and nitrogen metabolism in actinomycetes. Moreover, combinatorial engineering of SACE_4839 and nmrR in the high-yield S. erythraea WB resulted in a 68.8% increase in erythromycin A production. This investigation deepens the understanding of complicated regulatory network for erythromycin biosynthesis. Key points: • SACE_4839 and NmrR had opposite contributions to erythromycin biosynthesis. • NmrR was first identified as a homolog of another nitrogen regulator NmrA. • Cross regulation between SACE_4839 and NmrR was revealed. [ABSTRACT FROM AUTHOR]

A urea-utilizing bacterium, designated Q2-2 T, was isolated from landfill. Cells of strain Q2-2 T were Gram stain-negative, aerobic, short-rod bacteria. Strain Q2-2 T was observed to grow at a temperature range of 15–37℃ (optimum 30 ℃), a pH range of 5.5–9.5 (optimum pH 8.0) and 0–4% (w/v) NaCl (optimum 1%). The major respiratory quinone was Q-8, and the major polar lipids were diphosphatidyl glycerol, phosphatidylethanolamine, phosphatidylmethylethanolamine, and phosphatidyl glycerol. Based on the 16S rRNA gene sequence, strain Q2-2 T had the highest similarity with Paracandidimonas caeni 24 T (98.0%), followed by Pusillimonas soli MJ07T (97.5%), Parapusillimonas granuli Ch07T (97.2%), Pusillimonas ginsengisoli DCY25T (97.1%) and Paracandidimonas soli IMT-305 T (96.4%). The ANI values between strain Q2-2 T and the above related type strains were 71.02%, 73.52%, 74.32%, 74.59% and 72.29%, respectively. The DNA G + C content of strain Q2-2 T was 61.1%. Therefore, strain Q2-2 T represents a novel species of the genus Paracandidimonas, for which the name Paracandidimonas lactea sp. nov. (type strain Q2-2 T = CGMCC 1.19179 T = JCM 34906 T) is proposed. [ABSTRACT FROM AUTHOR]

Background: Postmenopausal osteoporosis (PMO) is a chronic condition characterized by decreased bone strength. This study aims to investigate the effects and mechanisms of the combination of Butyricicoccus pullicaecorum (Bp) and 3-hydroxyanthranilic acid (3-HAA) on PMO.The effects of Bp and 3-HAA on PMO were evaluated in ovariectomized (OVX) rats by assessing stereological parameters, femur microstructure, and autophagy levels. The T helper (Th) 17/Regulatory T (Treg) cells of rats were detected using flow cytometric analysis. Furthermore, the impact of Bp and 3-HAA on the gut microbiota of rats was assessed using 16S rRNA gene sequencing. The correlation between the gut microbiota of rats and Th17/Treg immune factors, as well as femoral stereo parameters, was separately assessed using Spearman rank correlation analysis.Bp and 3-HAA treatments protected OVX rats by promoting osteogenesis and inhibiting autophagy. Compared to the Sham group, OVX rats showed an increase in Th17 cells and a decrease in Treg cells. Bp and 3-HAA reversed these changes. Enterorhabdus and Pseudomonas were significantly enriched in OVX rats. Bp and 3-HAA regulated the gut microbiota of OVX rats, enriching pathways related to nutrient metabolism and immune function. There was a correlation between the gut microbiota and the Th17/Treg, as well as femoral stereo parameters. The concurrent administration of Bp and 3-HAA medication facilitated the enrichment of gut microbiota associated with the improvement of PMO.The combination therapy of Bp and 3-HAA can prevent PMO by modulating the gut microbiota and restoring Th17/Treg immune homeostasis.Methods: Postmenopausal osteoporosis (PMO) is a chronic condition characterized by decreased bone strength. This study aims to investigate the effects and mechanisms of the combination of Butyricicoccus pullicaecorum (Bp) and 3-hydroxyanthranilic acid (3-HAA) on PMO.The effects of Bp and 3-HAA on PMO were evaluated in ovariectomized (OVX) rats by assessing stereological parameters, femur microstructure, and autophagy levels. The T helper (Th) 17/Regulatory T (Treg) cells of rats were detected using flow cytometric analysis. Furthermore, the impact of Bp and 3-HAA on the gut microbiota of rats was assessed using 16S rRNA gene sequencing. The correlation between the gut microbiota of rats and Th17/Treg immune factors, as well as femoral stereo parameters, was separately assessed using Spearman rank correlation analysis.Bp and 3-HAA treatments protected OVX rats by promoting osteogenesis and inhibiting autophagy. Compared to the Sham group, OVX rats showed an increase in Th17 cells and a decrease in Treg cells. Bp and 3-HAA reversed these changes. Enterorhabdus and Pseudomonas were significantly enriched in OVX rats. Bp and 3-HAA regulated the gut microbiota of OVX rats, enriching pathways related to nutrient metabolism and immune function. There was a correlation between the gut microbiota and the Th17/Treg, as well as femoral stereo parameters. The concurrent administration of Bp and 3-HAA medication facilitated the enrichment of gut microbiota associated with the improvement of PMO.The combination therapy of Bp and 3-HAA can prevent PMO by modulating the gut microbiota and restoring Th17/Treg immune homeostasis.Results: Postmenopausal osteoporosis (PMO) is a chronic condition characterized by decreased bone strength. This study aims to investigate the effects and mechanisms of the combination of Butyricicoccus pullicaecorum (Bp) and 3-hydroxyanthranilic acid (3-HAA) on PMO.The effects of Bp and 3-HAA on PMO were evaluated in ovariectomized (OVX) rats by assessing stereological parameters, femur microstructure, and autophagy levels. The T helper (Th) 17/Regulatory T (Treg) cells of rats were detected using flow cytometric analysis. Furthermore, the impact of Bp and 3-HAA on the gut microbiota of rats was assessed using 16S rRNA gene sequencing. The correlation between the gut microbiota of rats and Th17/Treg immune factors, as well as femoral stereo parameters, was separately assessed using Spearman rank correlation analysis.Bp and 3-HAA treatments protected OVX rats by promoting osteogenesis and inhibiting autophagy. Compared to the Sham group, OVX rats showed an increase in Th17 cells and a decrease in Treg cells. Bp and 3-HAA reversed these changes. Enterorhabdus and Pseudomonas were significantly enriched in OVX rats. Bp and 3-HAA regulated the gut microbiota of OVX rats, enriching pathways related to nutrient metabolism and immune function. There was a correlation between the gut microbiota and the Th17/Treg, as well as femoral stereo parameters. The concurrent administration of Bp and 3-HAA medication facilitated the enrichment of gut microbiota associated with the improvement of PMO.The combination therapy of Bp and 3-HAA can prevent PMO by modulating the gut microbiota and restoring Th17/Treg immune homeostasis.Conclusion: Postmenopausal osteoporosis (PMO) is a chronic condition characterized by decreased bone strength. This study aims to investigate the effects and mechanisms of the combination of Butyricicoccus pullicaecorum (Bp) and 3-hydroxyanthranilic acid (3-HAA) on PMO.The effects of Bp and 3-HAA on PMO were evaluated in ovariectomized (OVX) rats by assessing stereological parameters, femur microstructure, and autophagy levels. The T helper (Th) 17/Regulatory T (Treg) cells of rats were detected using flow cytometric analysis. Furthermore, the impact of Bp and 3-HAA on the gut microbiota of rats was assessed using 16S rRNA gene sequencing. The correlation between the gut microbiota of rats and Th17/Treg immune factors, as well as femoral stereo parameters, was separately assessed using Spearman rank correlation analysis.Bp and 3-HAA treatments protected OVX rats by promoting osteogenesis and inhibiting autophagy. Compared to the Sham group, OVX rats showed an increase in Th17 cells and a decrease in Treg cells. Bp and 3-HAA reversed these changes. Enterorhabdus and Pseudomonas were significantly enriched in OVX rats. Bp and 3-HAA regulated the gut microbiota of OVX rats, enriching pathways related to nutrient metabolism and immune function. There was a correlation between the gut microbiota and the Th17/Treg, as well as femoral stereo parameters. The concurrent administration of Bp and 3-HAA medication facilitated the enrichment of gut microbiota associated with the improvement of PMO.The combination therapy of Bp and 3-HAA can prevent PMO by modulating the gut microbiota and restoring Th17/Treg immune homeostasis. [ABSTRACT FROM AUTHOR]

Validamycin A (VAL-A) is a CN aminocyclitol antibiotic produced by Streptomyces hygroscopicus var. jinggangensis 5008, which has been widely used as antifungal agent against rice sheath blight disease. VAL-A biosynthesis has been proven to be affected by γ-butyrolactone and temperature. Herein, we showed that GlnR, a global regulator in nitrogen metabolism, is specifically associated with valK-valA intergenic promoter region by DNA-affinity chromatography and MS-based protein identification. Subsequent EMSA and DNase I footprinting assays revealed two GlnR binding sites in this promoter region. Targeted disruption of glnR in S. hygroscopicus 5008 led to a significant increase in the transcription of VAL-A structural genes, albeit the VAL-A production was reduced by 80 % and the sporulation of the mutant was impaired. Compared with the wild-type 5008, site-specific mutagenesis of GlnR binding site I enhanced VAL-A production by 2.5-fold, whereas the mutation of GlnR binding site II resulted in a 50 % reduction of VAL-A yield. Moreover, tandem mutation of site I in the site II mutant led to a 66 % increase of VAL-A production. The result suggested that GlnR not only serves as an inhibitor by binding site I but also as an activator by binding site II for VAL-A biosynthesis. Furthermore, overexpression of glnR in the site I mutant JG45 improved VAL-A production for 41 % compared with the control strain containing the vector. Therefore, the obtained data illustrate a novel regulatory feature of the global regulator GlnR. GlnR is firstly proved to act simultaneously as an activator and a repressor in validamycin biosynthesis by binding to different loci within a promoter region of the gene cluster. [ABSTRACT FROM AUTHOR]

Source seeking problem has been faced in many fields, especially in search and rescue applications. We proposed a virtual structure-based spatial–temporal method to realize cooperative source seeking using multi-agents. Spatially, a circular formation is considered to gather collaborative information and estimate the gradient direction of the formation center. In terms of temporal information, we use the formation positions in time sequence to construct a virtual structure sequence. Then, we fuse the sequential gradient as a whole. Experimental results show that, compared with state-of-the-art, the proposed method can quickly and efficiently find the source so that the formation can minimize the movement distance during the moving process and increase the efficiency of source seeking. Numerical simulations confirm the efficiency of the scheme put forth. Compared with state-of-the-art source-seeking methods, the iterative steps of our proposed method are reduced by 20%, indicating that the method can find the signal source with higher efficiency and lower energy consumption, and better robustness. [ABSTRACT FROM AUTHOR]

Polyaniline/poly(vinyl alcohol)/TiO2 (PANI/PVA/TiO2) hybrid hydrogels with improved mechanical and electrochemical properties were fabricated via in situ oxidative polymerization of aniline (ANI) and in situ synthesized TiO2 with sol–gel method. Due to the combination of hydrogen bonds and electrostatic interactions among PANI, PVA, and TiO2, this inorganic hybrid crosslinking structures enabled the PANI/PVA/TiO2 hybrid hydrogel to possess reinforced tensile/compressive strength (26.5 kPa/8.2 MPa) and unprecedented self-healing performance. Moreover, with the optimized conductive pathways in the hybrid hydrogel, its conductivity was up to 1.38 S/m, which meets the requirement of being utilized as high-performance flexible solid-state supercapacitors. At current density of 0.5 A/g, the hydrogel-based supercapacitor provided a large capacitance of 41.0–127.5 F/g and a high energy density of 0.9–2.8 Wh/kg, which were superior to other flexible supercapacitors. The easily fabricated PANI/PVA/TiO2 conducting hydrogels provides a novel strategy to prepare hydrogel electrodes for flexible energy storage devices. [ABSTRACT FROM AUTHOR]

Saccharopolyspora erythraea, a mycelium-forming actinomycete, produces a clinically important antibiotic erythromycin. Extensive investigations have provided insights into erythromycin biosynthesis in S. erythraea, but knowledge of its morphogenesis remains limited. By gene inactivation and complementation strategies, the TetR-family transcriptional regulator SACE_0012 was identified to be a negative regulator of mycelium formation of S. erythraea A226. Detected by quantitative real-time PCR, the relative transcription of SACE_7115, the amfC homolog for an aerial mycelium formation protein, was dramatically increased in SACE_0012 mutant, whereas erythromycin biosynthetic gene eryA, a pleiotropic regulatory gene bldD, and the genes SACE_2141, SACE_6464, SACE_6040, that are the homologs to the sporulation regulators WhiA, WhiB, WhiG, were not differentially expressed. SACE_0012 disruption could not restore its defect of aerial development in bldD mutant, and also did not further accelerate the mycelium formation in the mutant of SACE_7040 gene, that was previously identified to be a morphogenesis repressor. Furthermore, the transcriptional level of SACE_0012 had not markedly changed in bldD and SACE_7040 mutant over A226. Taken together, these results suggest that SACE_0012 is a negative regulator of S. erythraea morphogenesis by mainly increasing the transcription of amfC gene, independently of the BldD regulatory system. [ABSTRACT FROM AUTHOR]

There are few commercially available β-nucleating agents (β-NAs) that can induce Polypropylene random copolymer (PPR) to produce large amounts of β-crystals at present. In this work, we discover that the Zinc Suberate (ZnSA) can effectively induce the formation of β-crystals for PPR and the relative β-crystals content (Kβ) can reach 0.82 when 0.2wt% ZnSA is added. The incorporation of ZnSA significantly decrease the size of spherulite and increase the crystallization rate, which are revealed by polarized optical microscopy (POM) images. Then, the effects of ZnSA on the isothermal and non-isothermal crystallization behavior of PPR at ultra-fast cooling rates and heating rates were investigated by Flash-DSC. Through the isothermal crystallization process, a bimodal relationship between the peak crystallization time and temperature was obtained. When the isothermal crystallization temperature is higher than 36 °C, ZnSA significantly increases the crystallization rate of PPR. According to the non-isothermal crystallization, we discover that the addition of ZnSA inhibits the formation of mesophase and the low cooling rate (< 10 °C·s−1) is more beneficial for the formation of β-crystals for PPR. In addition, β-crystals are not suitable to be characterized by rapid heating rate (> 300 °C·s−1) because β-crystals and α-crystals are not distinguished at rapid heating rate. This work is beneficial for deeply understanding the influence of β-NAs on crystallization behavior of PPR and providing guidance for the optimization of industrial production processes. [ABSTRACT FROM AUTHOR]

The Lrp and MarR families are two groups of transcriptional regulators widely distributed among prokaryotes. However, the hierarchical-regulatory relationship between the Lrp family and the MarR family remains unknown. Our previous study found that an Lrp (SACE_Lrp) from Saccharopolyspora erythraea indirectly repressed the biosynthesis of erythromycin. In this study, we characterized a novel MarR family protein (SACE_6745) from S. erythraea, which is controlled by SACE_Lrp and plays a direct regulatory role in erythromycin biosynthesis and export. SACE_Lrp directly regulated the expression of marR by specifically binding a precise site OM (5'-CTCCGGGAACCATT-3'). Gene disruption of marR increased the production of erythromycin by 45% in S. erythraea A226. We found that MarR has direct DNA-binding activity for the promoter regions of the erythromycin biosynthetic genes, as well as an ABC exporter SACE_2701-2702 which was genetically proved to be responsible for erythromycin efflux. Disruption of SACE_Lrp in industrial S. erythraea WB was an efficient strategy to enhance erythromycin production. Herein, we jointly engineered SACE_Lrp and its target MarR by deleting marR in WBΔSACE_Lrp, resulting in 20% increase in erythromycin yield in mutant WBΔLrpΔmarR compared to WBΔSACE_Lrp, and 39% to WB. Overall, our findings provide new insights into the hierarchical-regulatory relationship of Lrp and MarR proteins and new avenues for coordinating antibiotic biosynthesis and export by joint engineering regulators in actinomycetes. Key points: • The hierarchical-regulatory relationship between SACE_Lrp and MarR was identified. • MarR directly controlled the expression of erythromycin biosynthesis and export genes. • Joint engineering of SACE_Lrp-MarR regulatory element enhanced erythromycin production. [ABSTRACT FROM AUTHOR]

In this study, the halloysite nanotubes was characterized and the adsorption of Th(IV) and U(VI) on halloysite nanotubes was investigated as a function of contact time, adsorbent dosage, pH, ionic strength, initial U(VI) concentration and temperature using batch method. Meanwhile, the adsorption mechanism of uranium and thorium on halloysite nanotubes was discussed. The microscopic results displayed that halloysite nanotubes was tubular morphology and highly porous and high specific surface area of ca. 55.65 m2/g. The adsorption results showed that the adsorption of U(VI) and Th(IV) on halloysite nanotubes followed pseudo-second-order kinetic model. The strong pH dependent adsorption of U(VI) and Th(IV) displayed their strong surface complexation with the surface of halloysite nanotubes. The adsorption of Th(IV) and U(VI) increased with elevating temperature and was an endothermic and spontaneous process. The adsorption isotherms of Th(IV) and U(VI) can be better described by Freundlich and D–R model. The effect of ionic strength on the adsorption of thorium on halloysite nanotubes was much greater than that on uranium(almost unaffected), which suggested the adsorption of Th(IV) on halloysite nanotubes was most probably based on the formation of inner-sphere complexes, while that of U(VI) was based on the formation of outer-sphere complex on the edge surfaces. Th(IV) and U(VI) adsorption–desorption isotherm on halloysite nanotubes indicated adsorption process was irreversible. The selectivity order of adsorption by the halloysite nanotubes was Th(IV) > U(VI). The higher adsorption efficiency of the halloysite nanotubes for Th(IV) could be utilized for selective separation of Th(IV) from U(VI) aqueous with pH 4.1–4.3. The novel and environmentally friendly adsorption material is feasible to extract thorium from waste aqueous solution. [ABSTRACT FROM AUTHOR]

Leucine-responsive regulatory proteins (Lrps) are a family of transcription factors involved in diverse biological processes in bacteria. So far, molecular mechanism of Lrps for regulating antibiotics biosynthesis in actinomycetes remains largely unexplored. This study, for the first time in Streptomyces lincolnensis, identified an Lrp (named as SLCG_Lrp) associated with lincomycin production. SLCG_Lrp was validated to be a positive regulator for lincomycin biosynthesis by directly stimulating transcription of two structural genes (lmbA and lmbV), three resistance genes (lmrA, lmrB and lmrC), and a regulatory gene (lmbU) within the lincomycin biosynthetic gene (lin) cluster. SLCG_Lrp was transcriptionally self-inhibited and triggered the expression of its adjacent gene SLCG_3127 encoding a LysE superfamily protein. Further, the binding site of SLCG_Lrp in the intergenic region of SLCG_3127 and SLCG_Lrp was precisely identified. Inactivation of SLCG_3127 in S. lincolnensis resulted in yield improvement of lincomycin, which was caused by intracellular accumulation of proline and cysteine. Arginine and phenylalanine were identified as specific regulatory ligands, respectively, to reduce and promote DNA-binding affinity of SLCG_Lrp. We further found that SLCG_Lrp was directly repressed by SLCG_2919, the first identified transcription factor outside lin cluster for lincomycin production. Therefore, our findings revealed SLCG_Lrp-mediated transcriptional regulation of lincomycin biosynthesis. This study extends the understanding of molecular mechanisms underlying lincomycin biosynthetic regulation. [ABSTRACT FROM AUTHOR]

Lrp/AsnC family regulators have been found in many bacteria as crucial regulators controlling diverse cellular processes. By genomic alignment, we found that SCO3361, an Lrp/AsnC family protein from Streptomyces coelicolor, shared the highest similarity to the SACE_Lrp from Saccharopolyspora erythraea. Deletion of SCO3361 led to dramatic reduction in actinorhodin (Act) production and delay in aerial mycelium formation and sporulation on solid media. Dissection of the mechanism underlying the function of SCO3361 in Act production revealed that it altered the transcription of the cluster-situated regulator gene actII-ORF4 by directly binding to its promoter. SCO3361 was an auto-regulator and simultaneously activated the transcription of its adjacent divergently transcribed gene SCO3362. SCO3361 affected aerial hyphae formation and sporulation of S. coelicolor by activating the expression of amfC, whiB, and ssgB. Phenylalanine and cysteine were identified as the effector molecules of SCO3361, with phenylalanine reducing the binding affinity, whereas cysteine increasing it. Moreover, interactional regulation between SCO3361 and SACE_Lrp was discovered for binding to each other's target gene promoter in this work. Our findings indicate that SCO3361 functions as a pleiotropic regulator controlling secondary metabolism and morphological development in S. coelicolor. [ABSTRACT FROM AUTHOR]