Genomics and resequencing of Fagopyrum dibotrys from different geographic regions reveals species evolution and genetic diversity.

Fagopyrum dibotrys, belonging to the family Polygonaceae and genus Fagopyrum, is used in traditional Chinese medicine and is rich in beneficial components, such as flavonoids. As its abundant medicinal value has become increasingly recognized, its excessive development poses a considerable challenge to wild germplasm resources, necessitating artificial cultivation and domestication. Considering these factors, a high-quality genome of F. dibotrys was assembled and the evolutionary relationships within Caryophyllales were compared, based on which 58 individual samples of F. dibotrys were re-sequenced. We found that the samples could be categorized into three purebred populations and regions distributed at distinct elevations. Our varieties were cultivated from the parental populations of the subpopulation in central Yunnan. F. dibotrys is speculated to have originated in the high-altitude Tibetan Plateau region, and that its combination with flavonoids can protect plants against ultraviolet radiation; this infers a subpopulation with a high accumulation of flavonoids. This study assembled a high-quality genome and provided a theoretical foundation for the future introduction, domestication, and development of cultivated varieties of F. dibotrys.

The role of DsbA and PepP genes in the environmental tolerance and virulence factors of Cronobacter sakazakii.

Cronobacter sakazakii, an opportunity foodborne pathogen, could contaminate a broad range of food materials and cause life-threatening symptoms in infants. The bacterial envelope structure contribute to bacterial environment tolerance, biofilm formation and virulence in various in Gram-negative bacteria. DsbA and PepP are two important genes related to the biogenesis and stability of bacterial envelope. In this study, the DsbA and PepP were deleted in C. sakazakii to evaluate their contribution to stress tolerance and virulence of the pathogen. The bacterial environment resistance assays showed DsbA and PepP are essential in controlling C. sakazakii resistance to heat and desiccation in different mediums, as well as acid, osmotic, oxidation and bile salt stresses. DsbA and PepP also played an important role in regulating biofilm formation and motility. Furthermore, DsbA and PepP deletion weaken C. sakazakii adhesion and invasion in Caco-2, intracellular survival and replication in RAW 264.7. qRT-PCR results showed that DsbA and PepP of C. sakazakii played roles in regulating the expression of several genes associated with environment stress tolerance, biofilm formation, bacterial motility and cellular invasion. These findings indicate that DsbA and PepP played an important regulatory role in the environment resisitance, biofilm formation and virulence of C. sakazakii, which enrich understanding of genetic determinants of adaptability and virulence of the pathogen.

Wnt5a-mediated autophagy contributes to the epithelial-mesenchymal transition of human bronchial epithelial cells during asthma.

BACKGROUND: The epithelial-mesenchymal transition (EMT) of human bronchial epithelial cells (HBECs) is essential for airway remodeling during asthma. Wnt5a has been implicated in various lung diseases, while its role in the EMT of HBECs during asthma is yet to be determined. This study sought to define whether Wnt5a initiated EMT, leading to airway remodeling through the induction of autophagy in HBECs. METHODS: Microarray analysis was used to investigate the expression change of WNT5A in asthma patients. In parallel, EMT models were induced using 16HBE cells by exposing them to house dust mites (HDM) or interleukin-4 (IL-4), and then the expression of Wnt5a was observed. Using in vitro gain- and loss-of-function approaches via Wnt5a mimic peptide FOXY5 and Wnt5a inhibitor BOX5, the alterations in the expression of the epithelial marker E-cadherin and the mesenchymal marker protein were observed. Mechanistically, the Ca2+/CaMKII signaling pathway and autophagy were evaluated. An autophagy inhibitor 3-MA was used to examine Wnt5a in the regulation of autophagy during EMT. Furthermore, we used a CaMKII inhibitor KN-93 to determine whether Wnt5a induced autophagy overactivation and EMT via the Ca2+/CaMKII signaling pathway. RESULTS: Asthma patients exhibited a significant increase in the gene expression of WNT5A compared to the healthy control. Upon HDM and IL-4 treatments, we observed that Wnt5a gene and protein expression levels were significantly increased in 16HBE cells. Interestingly, Wnt5a mimic peptide FOXY5 significantly inhibited E-cadherin and upregulated α-SMA, Collagen I, and autophagy marker proteins (Beclin1 and LC3-II). Rhodamine-phalloidin staining showed that FOXY5 resulted in a rearrangement of the cytoskeleton and an increase in the quantity of stress fibers in 16HBE cells. Importantly, blocking Wnt5a with BOX5 significantly inhibited autophagy and EMT induced by IL-4 in 16HBE cells. Mechanistically, autophagy inhibitor 3-MA and CaMKII inhibitor KN-93 reduced the EMT of 16HBE cells caused by FOXY5, as well as the increase in stress fibers, cell adhesion, and autophagy. CONCLUSION: This study illustrates a new link in the Wnt5a-Ca2+/CaMKII-autophagy axis to triggering airway remodeling. Our findings may provide novel strategies for the treatment of EMT-related diseases.

Combining metabolomics with network pharmacology to reveal the therapeutic mechanism of Dingchuan Decoction in rats with OVA-induced allergic asthma.

Dingchuan Decoction (DCD) is a traditional Chinese medicine prescription commonly used in the treatment of asthma, but the mechanism of DCD in treating asthma has not yet been determined. In this study, we employed a combination of metabolomics and network pharmacology to investigate the mechanism of DCD in treating asthma. An allergic asthma rat model was induced by ovalbumin (OVA). Metabolomics based on 1H NMR and UHPLC-MS was used to identify differential metabolites and obtain the major metabolic pathways and potential targets. Network pharmacology was utilized to explore potential targets of DCD for asthma treatment. Finally, the results of metabolomics and network pharmacology were integrated to obtain the key targets and metabolic pathways of DCD for the therapy of asthma, and molecular docking was utilized to validate the key targets. A total of 76 important metabolites and 231 potential targets were identified through metabolomics. Using network pharmacology, 184 potential therapeutic targets were obtained. These 184 targets were overlaid with the 231 potential targets obtained through metabolomics and were analyzed in conjunction with metabolic pathways. Ultimately, the key targets were identified as aldehyde dehydrogenase 2 (ALDH2) and amine oxidase copper-containing 3 (AOC3), and the relevant metabolic pathways affected were glycolysis and gluconeogenesis as well as arginine and proline metabolism. Molecular docking showed that the key targets had high affinity with the relevant active ingredients in DCD, which further demonstrated that DCD may exert therapeutic effects by acting on the key targets. The present study demonstrated that DCD can alleviate OVA-induced allergic asthma and that DCD may have a therapeutic effect by regulating intestinal flora and polyamine metabolism through its effects on ALDH2 and AOC3.

Intestinal linoleic acid contributes to the protective effects of Akkermansia muciniphila against Listeria monocytogenes infection in mice.

Akkermansia muciniphila pretreatment mitigated Listeria monocytogenes infection in mice. A. muciniphila improved gut microbiota disturbed by L. monocytogenes infection and significantly increased the level of intestinal linoleic acid in mice. Linoleic acid strengthened the intestinal epithelial barrier and reduced pathogen translocation partly by regulating NF-κB/MLCK pathway in a GPR40-dependent manner.

The Brassinosteroid Receptor StBRI1 Promotes Tuber Development by Enhancing Plasma Membrane H+-ATPase Activity in Potato.

The brassinosteroid (BR) receptor BRASSINOSTEROID-INSENSITIVE 1 (BRI1) plays a critical role in plant growth and development. Although much is known about how BR signaling regulates growth and development in many crop species, the role of StBRI1 in regulating potato (Solanum tuberosum) tuber development is not well understood. To address this question, a series of comprehensive genetic and biochemical methods were applied in this investigation. It was determined that StBRI1 and Solanum tuberosum PLASMA MEMBRANE (PM) PROTON ATPASE2 (PHA2), a PM-localized proton ATPase, play important roles in potato tuber development. The individual overexpression of StBRI1 and PHA2 led to a 22% and 25% increase in tuber yield per plant, respectively. Consistent with the genetic evidence, in vivo interaction analysis using double transgenic lines and PM H+-ATPase activity assays indicated that StBRI1 interacts with the C-terminus of PHA2, which restrains the intramolecular interaction of the PHA2 C-terminus with the PHA2 central loop to attenuate autoinhibition of PM H+-ATPase activity, resulting in increased PHA2 activity. Furthermore, the extent of PM H+-ATPase autoinhibition involving phosphorylation-dependent mechanisms corresponds to phosphorylation of the penultimate Thr residue (Thr-951) in PHA2. These results suggest that StBRI1 phosphorylates PHA2 and enhances its activity, which subsequently promotes tuber development. Altogether, our results uncover a BR-StBRI1-PHA2 module that regulates tuber development and suggest a prospective strategy for improving tuberous crop growth and increasing yield via the cell surface-based BR signaling pathway.

Curved and Annular Diaphragm Coupled Piezoelectric Micromachined Ultrasonic Transducers for High Transmit Biomedical Applications.

In this paper, we present a novel three-dimensional (3D) coupled configuration of piezoelectric micromachined ultrasound transducers (pMUTs) by combing a curved and an annular diaphragm for transmit performance optimization in biomedical applications. An analytical equivalent circuit model (EQC) is developed with varied excitation methods to incorporate the acoustic-structure coupling of the curved and annular diaphragm-coupled pMUTs (CAC-pMUTs). The model-derived results align well with the reference simulated by the finite element method (FEM). Using this EQC model, we optimize the key design parameters of the CAC-pMUTs in order to improve the output sound pressure, including the width of the annular membrane, the thickness of the passive layer, and the phase difference of the driving voltage. In the anti-phase mode, the designed CAC-pMUTs demonstrate a transmit efficiency 285 times higher than that of single annular pMUTs. This substantial improvement underscores the potential of CAC-pMUTs for large array applications.

Nicotine aggravates pancreatic fibrosis in mice with chronic pancreatitis via mitochondrial calcium uniporter.

INTRODUCTION: This study aimed to investigate the effects of nicotine on the activation of pancreatic stellate cells (PSCs) and pancreatic fibrosis in chronic pancreatitis (CP), along with its underlying molecular mechanisms. METHODS: This was an in vivo and in vitro study. In vitro, PSCs were cultured to study the effects of nicotine on their activation and oxidative stress. Transcriptome sequencing was performed to identify potential signaling pathways involved in nicotine action. And the impact of nicotine on mitochondrial Ca2+ levels and Ca2+ transport-related proteins in PSCs was analyzed. The changes in nicotine effects were observed after the knockdown of the mitochondrial calcium uniporter (MCU) in PSCs. In vivo experiments were conducted using a mouse model of CP to assess the effects of nicotine on pancreatic fibrosis and oxidative stress in mice. The alterations in nicotine effects were observed after treatment with the MCU inhibitor Ru360. RESULTS: In vitro experiments demonstrated that nicotine promoted PSCs activation, characterized by increased cell proliferation, elevated α-SMA and collagen expression. Nicotine also increased the production of reactive oxygen species (ROS) and cellular malondialdehyde (MDA), exacerbating oxidative stress damage. Transcriptome sequencing revealed that nicotine may exert its effects through the calcium signaling pathway, and it was verified that nicotine elevated mitochondrial Ca2+ levels and upregulated MCU expression. Knockdown of MCU reversed the effects of nicotine on mitochondrial calcium homeostasis, improved mitochondrial oxidative stress damage and structural dysfunction, thereby alleviating the activation of PSCs. In vivo validation experiments showed that nicotine significantly aggravated pancreatic fibrosis in CP mice, promoted PSCs activation, exacerbated pancreatic tissue oxidative stress, and increased MCU expression. However, treatment with Ru360 significantly mitigated these effects. CONCLUSIONS: This study confirms that nicotine upregulates the expression of MCU, leading to mitochondrial calcium overload and exacerbating oxidative stress in PSCs, and ultimately promoting PSCs activation and exacerbating pancreatic fibrosis in CP.

Comprehensive Analysis of 11 Species of Euodia (Rutaceae) by Untargeted LC-IT-TOF/MS Metabolomics and In Vitro Functional Methods.

The Euodia genus comprises numerous untapped medicinal plants that warrant thorough evaluation for their potential as valuable natural sources of herbal medicine or food flavorings. In this study, untargeted metabolomics and in vitro functional methods were employed to analyze fruit extracts from 11 significant species of the Euodia genus. An investigation of the distribution of metabolites (quinolone and indole quinazoline alkaloids) in these species indicated that E. rutaecarpa (Euodia rutaecarpa) was the most widely distributed species, followed by E. compacta (Euodia compacta), E. glabrifolia (Euodia glabrifolia), E. austrosinensis (Euodia austrosinensis), and E. fargesii (Euodia fargesii). There have been reports on the close correlation between indole quinazoline alkaloids and their anti-tumor activity, especially in E. rutaecarpa fruits which exhibit effectiveness against various types of cancer, such as SGC-7901, Hela, A549, and other cancer cell lines. Additionally, the E. rutaecarpa plant contains indole quinazoline alkaloids, which possess remarkable antibacterial properties. Our results offer novel insights into the utilization of Euodia resources in the pharmaceutical industry.

Reconfigurable perovskite X-ray detector for intelligent imaging.

X-ray detection is widely used in various applications. However, to meet the demand for high image quality and high accuracy diagnosis, the raw data increases and imposes challenges for conventional X-ray detection hardware regarding data transmission and power consumption. To tackle these issues, we present a scheme of in-X-ray-detector computing based on CsPbBr3 single-crystal detector with convenient polarity reconfigurability, good linear dynamic range, and robust stability. The detector features a stable trap-free device structure and achieves a high linear dynamic range of 106 dB. As a result, the detector could achieve edge extraction imaging with a data compression ratio of ~50%, and could also be programmed and trained to perform pattern recognition tasks with a high accuracy of 100%. Our research shows that in-X-ray-detector computing can be used in flexible and complex scenarios, making it a promising platform for intelligent X-ray imaging.

PHGDH knockdown increases sensitivity to SR1, an aryl hydrocarbon receptor antagonist, in colorectal cancer by activating the autophagy pathway.

Colorectal cancer (CRC) has emerged as the third most prevalent and second deadliest cancer worldwide. Metabolic reprogramming is a key hallmark of cancer cells. Phosphoglycerate dehydrogenase (PHGDH) is over-expressed in multiple cancers, including CRC. Although the role of PHGDH in metabolism has been extensively investigated, its effects on CRC development remains to be elucidated. In the present study, it was demonstrated that PHGDH expression was significantly up-regulated in colorectal cancer. PHGDH expression was positively correlated with that of the aryl hydrocarbon receptor (AhR) and its target genes, CYP1A1 and CYP1B1, in CRC cells. Knockdown of PHGDH reduced AhR levels and activity, as well as the ratio of reduced to oxidized glutathione. The selective AhR antagonist stemregenin 1 induced cell death through reactive oxygen species-dependent autophagy in CRC cells. PHGDH knockdown induced CRC cell sensitivity to stemregenin 1 via the autophagy pathway. Our findings suggest that PHGDH modulates AhR signaling and the redox-dependent autophagy pathway in CRC, and that the combination of inhibition of both PHGDH and AhR may be a novel therapeutic strategy for CRC.

A comprehensive quality evaluation strategy of Shensong Yangxin capsules based on qualitative, fingerprint and quantitative analyses.

Shensong Yangxin capsule (SSYXC), an effective Chinese patent medicine, has been recorded in the Chinese Pharmacopeia, mainly for the treatment of coronary heart disease and ventricular premature beat. To further complete the quality evaluation of SSYXC, a comprehensive analysis strategy was established. Firstly, the components of SSYXC were qualitatively analysed using ultra-high- performance liquid chromatography-Fourier transform ion cyclotron resonance mass spectrometry. A total of 134 compounds were identified or tentatively characterized. Additionally, the fingerprint of SSYXC was established by HPLC, and the similarity of 10 batches of SSYXC was elucidated by similarity analysis. The result indicated that the consistency of chemical composition is good. Finally, to enhance the quality control of SSYXC, according to the results of the fingerprint analysis, the contents of the seven active components was determined, comprising morroniside, loganin, paeoniflorin, salvianolic acid B, palmatine hydrochloride, berberine hydrochloride and tanshinone IIA. In conclusion, the established method, comprising identification of components, fingerprint analysis and quantification of multicomponents, can be sensitively and comprehensively applied to the quality evaluation of SSYXC, which can provide chemical ingredients bases for quality control and the pharmacodynamic mechanism of SSYXC, which could serve as a benchmark for controlling the quality of other Chinese patent medicines.

Polysaccharides from Phellinus linteus attenuate type 2 diabetes mellitus in rats via modulation of gut microbiota and bile acid metabolism.

Type 2 diabetes mellitus (T2DM) is the most prevalent metabolic disorder. Polysaccharides from Phellinus linteus (PLP) have been found to have anti-diabetes effects, but the mechanism has not been elucidated. The purpose of this study was to investigate the mechanism of PLP on T2DM through the gut microbiota and bile acids metabolism. The T2DM rat model was induced by a high-fat high-carbohydrate (HFHC) diet and streptozocin (30 mg/kg). We found that PLP ameliorated diabetes symptoms. Besides, PLP intervention increased the abundance of g_Bacteroides, g_Parabacteroides, and g_Alistioes, which are associated with the biosynthesis of short-chain fatty acids (SCFAs) and bile acids (BAs) metabolism. Meanwhile, untargeted and targeted metabolomics indicated that PLP could regulate the composition of BAs and increase the levels of SCFAs. Real-time quantitative PCR (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA) were performed to analyze the expression levels of BAs metabolism enzymes in the liver. Finally, the results of correlation analysis and Glucagon-like peptide-1 (GLP-1) showed that PLP stimulated the release of GLP-1 by regulating SCFAs and BAs. In conclusion, this study demonstrated that PLP can regulate gut microbiota and BAs metabolism to promote GLP-1 secretion, thereby increasing insulin release, decreasing blood glucose and attenuating T2DM.

A comprehensive strategy for quality evaluation of Changan powder by fingerprinting combined with rapid qualitative and quantitative multi-ingredients profiling.

INTRODUCTION: Changan powder (CAP) is mainly used to treat various intestinal diseases. Few studies on CAP have been reported; therefore, it is necessary to clarify the material basis of CAP to lay the foundation for further elucidating its functional mechanism and support the rational use of drugs. OBJECTIVES: In the present study, we aimed to propose a methodology for the quality control of CAP based on qualitative and quantitative analysis of its components. METHODS: An ultra-performance liquid chromatography coupled with Fourier transform ion cyclotron resonance mass spectrometry (UPLC-FT-ICR-MS) method was developed to identify chemical components in CAP. In addition, fingerprints of 10 different batches of CAP were established, and quantitative analysis based on UPLC was performed to analyze the quality of CAP. RESULTS: A total of 58 compounds were preliminarily characterized. The similarity of 10 batches of CAP was greater than 0.995, and 23 common peaks were calibrated. Investigation of the quantitative analytical methodology showed that the four components had good linear relationships within their respective concentration ranges (r2 ≥ 0.9992), and the relative standard deviation (RSD) of precision and stability was less than 2%. The RSD of sample recovery ranged from 0.78% to 1.52%. CONCLUSION: The established method can quickly and effectively identify the chemical components of CAP and accurately quantify the known components in CAP. The established fingerprinting and content determination method is stable, reliable, and easy to operate and can be applied in quality control and in vivo research on CAP.

IAA-miR164a-NAC100L1 module mediates symbiotic incompatibility of cucumber/pumpkin grafted seedlings through regulating callose deposition.

Grafting is one of the key technologies to overcome the obstacles of continuous cropping, and improve crop yield and quality. However, the symbiotic incompatibility between rootstock and scion affects the normal growth and development of grafted seedlings after survival. The specific molecular regulation mechanism of graft incompatibility is still largely unclear. In this study, we found that the IAA-miR164a-NAC100L1 module induced callose deposition to mediate the symbiotic incompatibility of cucumber/pumpkin grafted seedlings. The incompatible combination (IG) grafting interface accumulated more callose, and the activity of callose synthase (CmCalS1) and IAA content were significantly higher than in the compatible combination (CG). Treatment with IAA polar transport inhibitor in the root of the IG plants decreased CmCalS activity and callose content. Furthermore, IAA negatively regulated the expression of Cm-miR164a, which directly targeted cleavage of CmNAC100L1. Interestingly, CmNAC100L1 interacted with CmCalS1 to regulate its activity. Further analysis showed that the interaction between CmNAC100L1 and CmCalS1 increased the activity of CmCalS1 in the IG plants but decreased it in the CG plants. Point mutation analysis revealed that threonine at the 57th position of CmCalS1 protein played a critical role to maintain its enzyme activity in the incompatible rootstock. Thus, IAA inhibited the expression of Cm-miR164a to elevate the expression of CmNAC100L1, which promoted CmNAC100L1 interaction with CmCalS1 to enhance CmCalS1 activity, resulting in callose deposition and symbiotic incompatibility of cucumber/pumpkin grafted seedlings.

Independent Manipulations of Transmitting and Receiving Channels by Nonreciprocal Programmable Metasurface.

The electromagnetic (EM) beam manipulations such as spatial scanning have always been the focus in information science and technology. Generally, the transmitting and receiving (T/R) beams of the same aperture should be coincident due to the reciprocal theory, and hence, more flexible controls of the spatial information are limited accordingly. Here, we propose a new approach to achieve independent controls of beam scanning in spatial T/R channels based on one aperture made by a nonreciprocal programmable metasurface. The meta-atom is designed to have independent propagation chains for T/R waves by introducing dual-direction power amplifiers (PAs) as the isolators for one-way transparency. A programmable phase shifter with a 360° coverage is loaded with the PA device in the transmitting or receiving chain to realize independent beam scanning in the T/R channels. A prototype of the proposed metasurface is fabricated, and independent beam scanning in the T/R channels is directly acquired with good performance in our measurements. In addition, a proof of concept of integrated sensing and auxiliary communications is accomplished to verify the validity of the presented method.

KDM4B down-regulation facilitated breast cancer cell stemness via PHGDH upregulation in H3K36me3-dependent manner.

Despite recent advances have been made in clinical treatments of breast cancer, the general prognosis of patients remains poor. Therefore, it is imperative to develop a more effective therapeutic strategy. Lysine demethylase 4B (KDM4B) has been reported to participate in breast cancer development recently, but its exact biological role in breast cancer remains unclear. Here, we observed that KDM4B was down-regulated in human primary BRCA tissues and the low levels of KDM4B expression were correlated with poor survival. Gain- and loss-of-function experiments showed that KDM4B inhibited the proliferation and metastasis of breast cancer cells. Besides, knockdown of KDM4B promoted the epithelial-mesenchymal transition (EMT) and cell stemness in breast cancer cells. Mechanistically, KDM4B down-regulates PHGDH by decreasing the enrichment of H3K36me3 on the promoter region of PHGDH. Knockdown of PHGDH could significantly reversed proliferation, migration, EMT, and cell stemness induced by KDM4B silencing in breast cancer cells. Collectively, we propose a model for a KDM4B/PHGDH axis that provides novel insight into breast cancer development, which may serve as a potential factor for predicting prognosis and a therapeutic target for breast cancer.

Current state of systematic reviews for platelet-rich plasma use in knee osteoarthritis.

BACKGROUND: Knee osteoarthritis (KOA) is a highly prevalent musculoskeletal disorder affecting millions of people. To date, there is no curative treatment for KOA other than joint arthroplasty. However, treatments such as platelet-rich plasma (PRP) have been proposed as a possible therapy, with increasing interest over the last decade. To date, there are no evidence-based guidelines in the use of PRP therapy for KOA, but there are numerous studies and systematic reviews (SRs) evaluating the usage of PRP in KOA. Since SRs are of great importance for clinical decision-making, it is necessary to access their methodological quality before any valid conclusions can be made. This study will evaluate the methodological quality of SRs on PRP therapy for KOA using a validated assessment tool known as AMSTAR 2, "A MeaSurement Tool to Assess systematic Reviews". HYPOTHESIS: It is hypothesized that the methodological quality of SRs will be moderate, whereby most of the SRs will provide an accurate summary of the results but will include more than one critical weakness as defined by the AMSTAR 2 checklist. PATIENTS AND METHODS: The MEDLINE, EMBASE, PubMed and Cochrane databases were searched from inception to May 2023. Two independent reviewers selected SRs that investigated the use of injection therapies for KOA. Descriptive statistical analysis was performed. AMSTAR 2 assessment was completed independently by the same reviewers. Cohen's kappa was calculated to measure interrater reliability. The quality of the studies was rated as "high", "moderate", "low", and "critically low". The overall confidence assessment was tabulated. RESULTS: Forty-one SRs were included in the analysis. The Cohen kappa was 0.88, indicating high interrater reliability. There were no "high" quality SRs identified. Seven SRs (17%) were of "low" quality, while the remainder (34 SRs, 83%) were rated as "critically low". CONCLUSION: The methodological quality of the selected SRs was suboptimal. Clinicians should critically appraise the SRs and interpret their conclusions with caution before making clinical decisions. This study supports future work of high-quality SRs regarding the use of PRP injections for KOA. LEVEL OF EVIDENCE: II.

Political embeddedness in public-private partnership for nature conservation: A land trust reserve case from China.

Private sector plays an increasingly vital role in nature conservation globally. This study explores the concept of political embeddedness, which suggests that governments and environmental nongovernmental organizations (ENGOs) can leverage each other's strengths to achieve both formal and informal goals. Using the case of Laohegou Nature Reserve in China, this study illustrated how the complementary advantages of the government and ENGOs form the foundation of a land trust reserve. Within the case, the study found that power and interest balance between the government and ENGOs during project implementation supported their formal cooperation in nature conservation. This study proposed a political perspective to elaborate power and interest in the formal and informal dimensions of nature conservation public-private partnership (PPP) project. Moreover, it noted that a balance of power between the government and ENGOs is essential in building partnership networks with inclusive interests.

Bile acids metabolism involved in the beneficial effects of Danggui Shaoyao San via gut microbiota in the treatment of CCl4 induced hepatic fibrosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Danggui Shaoyao San (DSS) is a traditional Chinese medicine (TCM) first recorded in the Synopsis of the Golden Chamber. DSS has proven efficacy in treating hepatic fibrosis (HF). However, the effects and mechanisms of DSS on HF are not clear. AIM OF THE STUDY: To investigate the effect of DSS on HF via gut microbiota and its metabolites (SCFAs, BAs). MATERIALS AND METHODS: HF rats were induced with CCl4 and treated with DSS. Firstly, the therapeutic efficacy of DSS in HF rats and the protection of gut barrier were assessed. Then, 16S rRNA gene sequencing and untargeted fecal metabolomics preliminarily explored the mechanism of DSS in treating HF, and identified different microbiota and metabolic pathways. Finally, targeted metabolomics and RT-qPCR were used to further validate the mechanism of DSS for HF based on the metabolism of SCFAs and BAs. RESULTS: After 8 weeks of administration, DSS significantly reduced the degree of HF. In addition, DSS alleviated inflammation in the ileum and reduced the levels of LPS and D-lactate. Furthermore, DSS altered the structure of gut microbiota, especially Veillonella, Romboutsia, Monoglobus, Parabacteroides, norank_f_Coriobacteriales_Incertae_Sedis. These bacteria have been linked to the production of SCFAs and the metabolism of BAs. Untargeted metabolomics suggested that DSS may play a role via BAs metabolism. Subsequently, targeted metabolomics and RT-qPCR further confirmed the key role of DSS in increasing SCFAs levels and regulating BAs metabolism. CONCLUSIONS: DSS can alleviate CCl4-induced HF and protect the gut barrier. DSS may exert its beneficial effects on HF by affecting the gut microbiota and its metabolites (SCFAs, BAs).