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Gwakhyangjeonggi-san (GJS) is a traditional herbal medicine used in East Asia for the treatment of symptoms involving lower intestinal abnormalities; however, the effects of GJS on innate immunity and its cellular mechanisms of action have not been elucidated. In this study, we assessed the immune-enhancing activity and underlying mechanisms of GJS using RAW 264.7 murine macrophages. The results showed that GJS treatment significantly increased the secretion of nitric oxide and cytokines and their mRNA expression in macrophage RAW 264.7 cells without causing cytotoxicity. GJS treatment also significantly increased the production of reactive oxygen species, as well as inducing phagocytic activity, adhesion function, and migration ability, all of which improved the immune response. In addition, GJS activated nuclear factor-κB by promoting the phosphorylation and degradation of inhibitor of nuclear factor-κB alpha. Furthermore, GJS markedly increased the phosphorylation of mitogen-activated protein kinase in RAW 264.7 cells. These findings indicate that GJS has potential value as a dietary supplement for strengthening immunity. [ABSTRACT FROM AUTHOR]

The transcription factor PsrA regulates fatty acid metabolism, the type III secretion system, and quinolone signaling quorum sensing system in Pseudomonas aeruginosa. To explore additional roles of PsrA in P. aeruginosa, this study engineered a P. aeruginosa PAO1 strain to carry a recombinant plasmid with the psrA gene (pMMBpsrA) and examined the impact of elevated psrA expression to the bacterium. Transcriptomic analysis revealed that PsrA significantly downregulated genes encoding the master quorum-sensing regulators, RhlR and LasR, and influenced many quorum-sensing-associated genes. The role of PsrA in quorum sensing was further corroborated by testing autoinducer synthesis in PAO1 [pMMBpsrA] using two reporter bacteria strains Chromobacterium violaceum CV026 and Escherichia coli [pSB1075], which respond to short- and long-chain acyl homoserine lactones, respectively. Phenotypic comparisons of isogenic psrA, lasR, and psrAlasR mutants revealed that the reduced elastase, caseinase, and swarming activity in PAO1 [pMMBpsrA] were likely mediated through LasR. Additionally, electrophoretic mobility shift assays demonstrated that recombinant PsrA could bind to the lasR promoter at a 5'-AAACGTTTGCTT-3' sequence, which displays moderate similarity to the previously reported consensus PsrA binding motif. Furthermore, the PsrA effector molecule oleic acid inhibited PsrA binding to the lasR promoter and restored several quorum sensing-related phenotypes to wild-type levels. These findings suggest that PsrA regulates certain quorum-sensing phenotypes by negatively regulating lasR expression, with oleic acid acting as a crucial signaling molecule. [ABSTRACT FROM AUTHOR]

The scientific quantification of the ecological effects of carbon emissions, the reduction of ecological risk (ER), and the evaluation of the interaction effect between carbon emissions and ER are the pivotal measures for ensuring the longevity and continuity of sustainability. However, a dearth of comprehensive and macro-level evaluations exist pertaining to the ER and carbon emissions within the entirety of the Yangtze River Economic Belt (YREB). We have constructed four distinct simulated scenarios within the YREB, which include natural development (ND), cultivated land protection (CLP), ecological conservation (EC), and low carbon (LC) scenarios. Based on the consideration of future uncertainty, we predicted LUCEs and ERI under different scenarios, and analyzed the spatial interaction effects of LUCEs and ERI from the dual perspectives of the spatial spillover effect and spatial coupling effect. The results showed that under the four outlined scenarios, encompassing diverse parameters, conversion possibilities, and areas subject to restrictions, the land utilization patterns of the YREB in 2030 have unveiled pronounced disparities. The LUCEs in the YREB showed significant spatial heterogeneity under the four scenarios; the maximum value was 6.65 under the CLP scenario and the minimum value was 4.65 under the LC scenario. The ER has the highest value under the ND scenario and the lowest value under LC scenario. Construction land is the largest contributor to increased LUCEs, and forest land is the form of terrestrial utilization that reduces the impact of LUCEs. In different scenarios, LUCEs have a significant negative spillover effect on ER, while the bidirectional spatial coupling effect between LUCEs and ERI presents significant differences. Under the LC scenario, land with a strong carbon sequestration capacity increased significantly, the fragmentation of water bodies was alleviated, and the CCD was the highest. This study offers scientific counsel for the sustainable development of various regions within the YREB, thereby fostering the achievement of a harmonious coexistence between the ecological milieu and economic development. [ABSTRACT FROM AUTHOR]

Sustainability has become an indispensable core consideration when nations formulate their development policies. This study delves into the dynamic correlations between ecosystem services (ESs) and localized Sustainable Development Goals (SDGs) in a typical hilly region in southern China. Various ESs were computed using the InVEST model, while spatial econometric models were employed to assess ES responses to SDG targets at the county, sectoral, and overall spatial levels. The findings revealed the following. (1) From 2005 to 2020, there were differences in the development rates of various SDG targets in Ganzhou. Except for SDG 15, which declined, the development of the other targets showed an overall increasing trend. The development of the various SDG targets was relatively balanced, but SDG 9 and SDG 7 had the highest growth rates, ranging from 9.4% to 10.7% and 9.4% to 10.3%, respectively. The comprehensive SDG assessment index exhibited significant spatiotemporal variation, with a general trend of higher values in the north and lower values in the south. (2) The local ES showed a delayed response to SDG 1 and SDG 2, but there was a significant positive response to SDG 3, SDG 4, SDG 6, SDG 8, and SDG 9. However, responses to SDG 7, SDG 11, SDG 13, and SDG 15 showed regional differences. This study not only provides valuable insights for sustainable development in Ganzhou and other regions of China but also offers Chinese perspectives and experiences that may inform global efforts towards SDG implementation. This study fills the gap in existing research by constructing a localized SDG indicator system and quantifying each SDG indicator, further exploring the response of the ES to each SDG in the region. Looking ahead, we anticipate further research to deepen the understanding of the relationship between ESs and SDG targets on a broader geographical scale and over longer timeframes, aiming to provide a more robust scientific foundation for building a harmonious coexistence between humans and nature in the future. [ABSTRACT FROM AUTHOR]

In Pseudomonas aeruginosa, an important opportunistic pathogen that causes numerous acute and chronic infections, the hybrid two-component system (TCS) regulates the swarming ability and biofilm formation with a multistep phosphorelay, and consists of hybrid-sensor histidine kinase (HK), histidine-containing phosphotransfer protein (Hpt) and response regulator (RR). In this work, two crystal structures of HptB and the receiver domain of HK PA1611 (PA1611REC) of P. aeruginosa have been determined in order to elucidate their interactions for the transfer of the phosphoryl group. The structure of HptB folds into an elongated four-helix bundle – helices α2, α3, α4 and α5, covered by the short N-terminal helix α1. The imidazole side chain of the conserved active-site histidine residue His57, located near the middle of helix α3, protrudes from the bundle and is exposed to solvent. The structure of PA1611REC possesses a conventional (β/α)5 topology with five-stranded parallel β-sheets folded in the central region, surrounded by five α-helices. The divalent Mg2+ ion is located in the negatively charged active-site cleft and interacts with Asp522, Asp565 and Arg567. The HptB–PA1611REC complex is further modeled to analyze the binding surface and interactions between the two proteins. The model shows a shape complementarity between the convex surface of PA1611REC and the kidney-shaped HptB with fewer residues and a different network involved in interactions compared with other TCS complexes, such as SLN1-R1/YPD1 from Saccharomyces cerevisiae and AHK5RD/AHP1 from Arabidopsis thaliana. These structural results provide a better understanding of the TCS in P. aeruginosa and could potentially lead to the discovery of a new treatment for infection.

OCD20015-V009 is an herbal mix of water-extracted Ginseng Radix, Poria (Hoelen), Rehmanniae Radix, Adenophorae Radix, Platycodi Radix, Crataegii Fructus, and Astragali Radix. In this study, its in vitro and in vivo antiviral activity and mechanisms against the influenza A virus were evaluated using a GFP-tagged influenza A virus (A/PR/8/34-GFP) to infect murine macrophages. We found that OCD20015-V009 pre-treatment substantially reduced A/PR/8/34-GFP replication. Also, OCD20015-V009 pre-treatment increased the phosphorylation of type-I IFN-related proteins TBK-1 and STAT1 and the secretion of pro-inflammatory cytokines TNF-α and IL-6 by murine macrophages. Moreover, OCD20015-V009 prophylactic administration increased IFN-stimulated genes-related 15, 20, and 56 and IFN-β mRNA in vitro. Thus, OCD20015-V009 likely modulates murine innate immune response via macrophages. This finding is potentially useful for developing prophylactics or therapeutics against the influenza A virus. Furthermore, pre-treatment with OCD20015-V009 decreased the mortality of the mice exposed to A/PR/8/34-GFP by 20% compared to that in the untreated animals. Thus, OCD20015-V009 stimulates the antiviral response in murine macrophages and mice to viral infections. Additionally, we identified chlorogenic acid and ginsenoside Rd as the antiviral components in OCD20015-V009. Further investigations are needed to elucidate the protective effects of active components of OCD20015-V009 against influenza A viruses.

The activation of microglial cells and their subsequent neuroinflammatory reactions are related to various degenerative brain diseases. Therefore, the regulation of microglial cell activation is an important point for the research of therapeutic agents for treating or preventing neurodegenerative disorders. Saussureae Radix (SR) is the root of Saussurea lappa Clarke, and it has been used for a long time as an herbal medicine in East Asia to treat indigestion and inflammation of the digestive system. In previous studies, however, the effect of SR ethanolic extract on microglial cell-mediated neuroinflammation was not fully explained. In this study, we explored the antineuroinflammatory activities and molecular mechanisms of SR in microglial cells stimulated with LPS (lipopolysaccharide). Our results illustrated that SR does not cause cytotoxicity and significantly weakens the production of nitric oxide (NO) and inflammatory cytokines. SR treatment also inhibited the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase- (COX-) 2, induced heme oxygenase- (HO-) 1, and activated the nuclear factor erythroid 2-related factor 2 (Nrf-2) pathway. In addition, SR significantly repressed the transcriptional activities of the nuclear factor- (NF-) κB and activator protein- (AP-) 1. Furthermore, SR effectively inhibited the phosphorylation of mitogen-activated protein kinase (MAPK) and Janus kinase (JAK)/signal transducer and activator of transcription (STAT). Isolation and high-performance liquid chromatography (HPLC) analysis indicated two major sesquiterpenoids (costunolide and dehydrocostuslactone). These compounds significantly inhibited the production of neuroinflammatory mediators and induced HO-1 expression. These findings show that SR could be a potential candidate for the treatment of inflammation-related degenerative brain diseases.

Background: Magnetic resonance imaging (MRI) has emerged as a promising tool for diagnosing prostate cancer. Magnetic resonance imaging/ultrasound (MRI/US) fusion target biopsy (TB) can increase the detection rate of clinically significant prostate cancer (csPC) and decrease the detection rate of clinically insignificant PC (ciPC) compared with systematic biopsy (SB). However, the MRI/US fusion biopsy had a steep learning curve. A new biopsy template, saturation TB (sTB), was reported to provide a cancer detection rate comparable to that of the combination of TB and SB. This study reports our experience with MRI/US fusion prostate biopsy and investigates the role of sTB in MRI/US fusion biopsy. Methods: We prospectively enrolled males with elevated prostate-specific antigen or abnormal digital rectal examination (DRE) and Prostate Imaging Reporting & Data System (PI-RADS) score ≥3 who underwent MRI/US fusion prostate biopsy in a tertiary referral center. We compared cancer detection rates among different biopsy templates, including TB, SB, sTB, and the combination of TB and SB. The biopsy results and complications were recorded. Results: The detection rate of csPC by sTB was significantly higher than that of TB (53% vs. 44%; p = 0.008) or SB (53% vs. 43%; p = 0.002). The median biopsy cores were 6, 15, and 26 for TB, sTB, and the combination of TB and SB, respectively. In other words, sTB could decrease 11 biopsy cores without compromising the cancer detection rate compared with the combination of TB and SB. There were no Clavien-Dindo score of ≥3 complications in any of the patients. Conclusion: The sTB template can overcome targeting errors during MRI/US fusion biopsy, offering a cancer detection rate equal to the combination of TB and SB with reduced biopsy cores.

Chronic inflammation and oxidative stress cause microglia to be abnormally activated in the brain, resulting in neurodegenerative diseases such as Alzheimer’s disease (AD). Menthae Herba (MH) has been widely used as a medicinal plant with antimicrobial, anti-inflammatory, and antioxidant properties. In this study, we sought to evaluate the effects of MH on the inflammatory response and possible molecular mechanisms in microglia stimulated with lipopolysaccharide (LPS). Transcriptional and translational expression levels of the proinflammatory factors were measured using ELISA, RT-qPCR, and Western blot analysis. MH extract inhibited the production of proinflammatory enzymes and mediators nitric oxide (NO), NO synthase, cyclooxygenase-2, tumor necrosis factor-α, and interleukin-6 in LPS-stimulated cells. Our molecular mechanism study showed that MH inhibited the production of reactive oxygen species (ROS) and the phosphorylation of mitogen-activated protein kinase and nuclear factor (NF)-κB. In contrast, MH activated HO-1 and its transcriptional factors, cAMP response element-binding protein (CREB), and the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathways. Thus, MH reduces ROS and NF-κB-mediated inflammatory signaling and induces CREB/Nrf2/HO-1-related antioxidant signaling in microglia. Together, these results may provide specific prospects for the therapeutic use of MH in the context of neuroinflammatory diseases, including AD.