Self-assembly of differentiated dental pulp stem cells facilitates spheroid human dental organoid formation and prevascularization.

BACKGROUND: The self-assembly of solid organs from stem cells has the potential to greatly expand the applicability of regenerative medicine. Stem cells can self-organise into microsized organ units, partially modelling tissue function and regeneration. Dental pulp organoids have been used to recapitulate the processes of tooth development and related diseases. However, the lack of vasculature limits the utility of dental pulp organoids. AIM: To improve survival and aid in recovery after stem cell transplantation, we demonstrated the three-dimensional (3D) self-assembly of adult stem cell-human dental pulp stem cells (hDPSCs) and endothelial cells (ECs) into a novel type of spheroid-shaped dental pulp organoid in vitro under hypoxia and conditioned medium (CM). METHODS: During culture, primary hDPSCs were induced to differentiate into ECs by exposing them to a hypoxic environment and CM. The hypoxic pretreated hDPSCs were then mixed with ECs at specific ratios and conditioned in a 3D environment to produce prevascularized dental pulp organoids. The biological characteristics of the organoids were analysed, and the regulatory pathways associated with angiogenesis were studied. RESULTS: The combination of these two agents resulted in prevascularized human dental pulp organoids (Vorganoids) that more closely resembled dental pulp tissue in terms of morphology and function. Single-cell RNA sequencing of dental pulp tissue and RNA sequencing of Vorganoids were integrated to analyse key regulatory pathways associated with angiogenesis. The biomarkers forkhead box protein O1 and fibroblast growth factor 2 were identified to be involved in the regulation of Vorganoids. CONCLUSION: In this innovative study, we effectively established an in vitro model of Vorganoids and used it to elucidate new mechanisms of angiogenesis during regeneration, facilitating the development of clinical treatment strategies.

A novel approach has been developed to produce pure plant-based gel soy yogurt by combining soy proteins (7S/11S), high pressure homogenization, and glycation reaction.

This research sought to examine how the physicochemical characteristics of soy globulins and different processing techniques influence the gel properties of soy yogurt. The goal was to improve these gel properties and rectify any texture issues in soy yogurt, ultimately aiming to produce premium-quality plant-based soy yogurt. In this research study, the investigation focused on examining the impact of 7S/11S, homogenization pressure, and glycation modified with glucose on the gel properties of soy yogurt. A plant-based soy yogurt with superior gel and texture properties was successfully developed using a 7S/11S globulin-glucose conjugate at a 1:3 ratio and a homogenization pressure of 110 MPa. Compared to soy yogurt supplemented with pectin or gelatin, this yogurt demonstrated enhanced characteristics. These findings provide valuable insights into advancing plant protein gels and serve as a reference for cultivating new soybean varieties by soybean breeding experts.

Added value of DCER-features to clinicopathologic model for predicting metachronous metastases in rectal cancer patients.

RATIONALE AND OBJECTIVES: The study aimed to investigate whether dynamic contrast-enhanced MRI parameters and preoperative radiological features (DCER-Features) add value to the clinicopathologic model for predicting metachronous metastases in rectal cancer patients. MATERIALS AND METHODS: From January 2014 to December 2020, 859 patients in the PACS system were retrospectively screened. Of the initial 722 patients with surgically confirmed rectal cancer and no synchronous metastases, 579 patients were excluded for various reasons such as lack of clinicopathological or radiological information. 143 patients were finally included in this study. And 73 Patients of them developed metachronous metastasis within five years. After stepwise multiple regression analyses, we constructed three distinct models. Model 1 was developed solely based on clinicopathological factors, and model 2 incorporated clinicopathological characteristics along with DCE-MRI parameters. Finally, model 3 was built on all available factors, including clinicopathological characteristics, DCE-MRI parameters, and radiological features based on rectal magnetic resonance imaging. The radiological features assessed in this study encompass tumor imaging staging, location, and circumferential resection margin (CRM) for primary tumors, as well as the number of visible lymph nodes and suspected metastatic lymph nodes. Receiver operating characteristic (ROC) and decision curve analysis (DCA) were conducted to evaluate whether the diagnostic efficiency was improved. RESULTS: The performance of model 3 (including clinicopathologic characteristics and DCER-Features) was the best (AUC: 0.856, 95% CI 0.778-0.886), whereas it was 0.796 (95% CI 0.720-0.828) for model 2 and 0.709 (95% CI 0.612-0.778) for model 1 (DeLong test: model 1 vs model 2, p = 0.004; model 2 vs model 3, p = 0.037; model 1 vs model 3, p < 0.001). The decision curves indicated that the net benefit of model 3 was higher than the other two models at each referral threshold. The calibration plot of the three models revealed an excellent predictive accuracy. CONCLUSION: This study suggests that DCER-Features have added value for the clinicopathological model to predict metachronous metastasis in patients with rectal cancers.

Activation of the insulin receptor by insulin-like growth factor 2.

Insulin receptor (IR) controls growth and metabolism. Insulin-like growth factor 2 (IGF2) has different binding properties on two IR isoforms, mimicking insulin's function. However, the molecular mechanism underlying IGF2-induced IR activation remains unclear. Here, we present cryo-EM structures of full-length human long isoform IR (IR-B) in both the inactive and IGF2-bound active states, and short isoform IR (IR-A) in the IGF2-bound active state. Under saturated IGF2 concentrations, both the IR-A and IR-B adopt predominantly asymmetric conformations with two or three IGF2s bound at site-1 and site-2, which differs from that insulin saturated IR forms an exclusively T-shaped symmetric conformation. IGF2 exhibits a relatively weak binding to IR site-2 compared to insulin, making it less potent in promoting full IR activation. Cell-based experiments validated the functional importance of IGF2 binding to two distinct binding sites in optimal IR signaling and trafficking. In the inactive state, the C-terminus of α-CT of IR-B contacts FnIII-2 domain of the same protomer, hindering its threading into the C-loop of IGF2, thus reducing the association rate of IGF2 with IR-B. Collectively, our studies demonstrate the activation mechanism of IR by IGF2 and reveal the molecular basis underlying the different affinity of IGF2 to IR-A and IR-B.

A meta-analysis comparing the efficacy of mineralized collagen-polymethylmethacrylate and polymethylmethacrylate bone cements in the treatment of vertebral compression fractures.

PURPOSE: Vertebral compression fractures are often treated with vertebroplasty, and filling the injured vertebrae with bone cement is a key part of vertebroplasty. This meta-analysis was performed to compare the clinical efficacy and safety of mineralized collagen-polymethylmethacrylate (MC-PMMA) and polymethylmethacrylate (PMMA) bone cement in the treatment of vertebral compression fractures by vertebroplasty. METHODS: A computerized search of the published literature on mineralized collagen-polymethylmethacrylate and polymethylmethacrylate bone cement in the treatment of vertebral compression fractures was conducted in the China National Knowledge Infrastructure (CNKI), Wanfang database, PubMed, Embase, and Cochrane Library. The search was carried out from the time the database was created to March 2023 and 2 researchers independently conducted literature searches to retrieve a total of 884 studies, of which 12 were included in this meta-analysis. Cochrane systematic review methods were used to assess the quality of the literature and a meta-analysis was performed using ReviewManager 5.4 software. RESULTS: The results of the present meta-analysis showed that in postoperative adjacent vertebral fractures [OR = 0.25; 95% CI (0.15, 0.41)], postoperative cement leakage [OR = 0.45; 95% CI (0.30, 0.68)], Oswestry Disability Index (ODI) scores in the first 3 days after surgery [OR = -0.22; 95% CI (-0.42, -0.03)], ODI score at 6-12 months postoperatively [OR = -0.65; 95% CI (-0.97, -0.32)], visual analog scale (VAS) score at 6-12 months postoperatively [OR = -0.21; 95% CI (-0.46, 0.04)], and 1-year postoperative CT values [OR = 5.56; 95% CI (3.06, 8.06)], the MC-PMMA bone cement group was superior to the PMMA bone cement group. However, the differences between the two groups were not statistically different in terms of cement filling time, cement filling volume, operation time, intraoperative bleeding, hospitalization time, postoperative (<1 week, 3-6 months) vertebral body posterior convexity Cobb's angle, postoperative (<1 week, 6-12 months) vertebral body anterior margin relative height, postoperative (≤3 days, 1-3 months) pain VAS score and postoperative (1-3 months) ODI score. CONCLUSIONS: Compared with PMMA bone cement, the application of MC-PMMA bone cement is advantageous in reducing postoperative complications (adjacent vertebral fracture rate, cement leakage rate), pain relief, and functional recovery in the long-term postoperative period (>6 months), but there is still a need for more high-quality randomized controlled studies to provide more adequate evidence.

A multifactorial study of mass movement in the hilly and gully Loess Plateau based on intensive field surveys and remote sensing techniques.

Mass movements, driven by various non-linearly correlated factors, exhibit high randomness, posing vast difficulties for field observations and subsequent investigations into the underlying mechanisms. In this study 157 mass movement incidents (including collapses, slump and spalling) and their primary influencing factors were surveyed in a small catchment of the hilly and gully Loess Plateau, China, through intensive field investigations and remote sensing techniques. The spatial pattern of mass movement and its relation with the influencing factors were assessed, while the relative impact of different factors was studied using the canonical correlation analysis. Results showed that 1) Mass movements predominantly occurred on gully slopes steeper than 70°. Collapses were the main type of mass movement, accounting for 87.9 % of the number of samples. 2) With regard to the impact of individual factors, rainstorms (rainfall intensity >50 mm day-1) significantly enhanced the occurrence frequency, erosion area and erosion volume of mass movement. The occurrence frequency and erosion area / volume were highest at a soil dry bulk density of 1.34 g cm-3 and 1.54 g cm-3, respectively. Mass movement occurred most frequently on unvegetated or unrooted gully slopes, where the resisting effect of vegetation on mass movement was absent. Gully slopes with smooth rather than rugged profiles were also found to be typical areas of mass movement. The occurrence frequency of mass movement decreased with the elevated topographic wetness index (TWI) and distance to slope top and increased with the distance to channels. 3) For the relative impact of different factors, rainfall and shear strength were key factors facilitating and resisting the onset of mass movement, respectively, while topography exerted the greatest influence on the erosion area and volume. This study revealed the relative influence of different factors on occurrence and scale of mass movement, providing a useful reference for modelling and control of the problem.

Myosteatosis is an independent risk factor for overt hepatic encephalopathy after transjugular intrahepatic portosystemic shunting.

OBJECTIVE: The relationship between skeletal muscle and adipose tissue compositions and risk of overt hepatic encephalopathy (OHE) following transjugular intrahepatic portosystemic shunt (TIPS) treatment needs to be investigated. METHODS: A total of 282 patients were collected from two medical centres. The median time of follow-up was 48.23 + 1.36 months and the first-year results of all patients after TIPS therapy were collected. The muscle and adipose tissue indices were quantified at the third lumbar vertebra level. Sarcopenia and myosteatosis were defined according to previous researches. Receiver operating characteristic curves, chi-square test, univariate and multivariate logistic regression analyses were employed to investigate the potential association between muscle and adipose indices, sarcopenia, myosteatosis and the risk of developing post-TIPS OHE. RESULTS: All skeletal muscle indices, adipose tissue indices and sarcopenia had limited associations with post-TIPS OHE. Myosteatosis (148 cases, 52.5%, 55 with OHE, 37.2%) was identified as an independent risk factor for post-TIPS OHE. with P  < 0.001 in Chi-square test, P  < 0.001, odds ratio (OR): 2.854, 95% confidence interval (CI): 1.632-4.993 in univariate logistic regression analyses, and P  = 0.007, OR: 2.372, 95% CI: 1.268-4.438 in multivariate logistic regression analyses, respectively. CONCLUSION: Our results showed that myosteatosis was proven as an independent risk factor for the development of post-TIPS OHE.

Global, regional, and national burden and trends of early-onset tracheal, bronchus, and lung cancer from 1990 to 2019.

BACKGROUND: Tracheal, bronchus, and lung cancer (TBL) is one of the main cancer health problems worldwide, but data on the burden and trends of early-onset tracheal, bronchus, and lung cancer (EO-TBL) are sparse. The aim of the present study was to provide the latest and the most comprehensive burden estimates of the EO-TBL cancer from 1990 to 2019. METHODS: Overall, we used data from the Global Burden of Disease (GBD) study in EO-TBL cancer from 1990 to 2019. Evaluation metrics included incidence, mortality, and disability-adjusted life years (DALYs). The joinpoint regression model was used to analyze the temporal trends. Decomposition analysis was employed to analyze the driving factors for EO-TBL cancer burden alterations. Bayesian age-period-cohort (BAPC) analysis was used to estimate trends in the next 20 years. RESULTS: The global age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), and age-standardized DALYs rate (ASDR) for EO-TBL cancer decreased significantly from 3.95 (95% uncertainty interval [UI]: 3.70-4.24), 3.41 (95% UI: 3.19-3.67), 158.68 (95% UI: 148.04-170.92) in 1990 to 2.82 (95% UI: 2.54-3.09), 2.28 (95% UI: 2.07-2.49), 106.47 (95% UI: 96.83-116.51) in 2019 with average annual percent change (AAPC) of -1.14% (95% confidence interval [CI]: -1.32 to -0.95), -1.37% (95% CI: -1.55 to -1.18), and - 1.35% (95% CI: -1.54 to -1.15) separately. The high and high-middle sociodemographic index (SDI) region had a higher burden of EO-TBL cancer but demonstrated a downward trend. The most prominent and significant upward trends were Southeast and South Asia, Africa, and women in the low SDI and low-middle SDI quintiles. At the regional and national level, there were significant positive correlations between ASDR, ASIR, ASMR, and SDI. Decomposition analysis showed that population growth and aging have driven the increase in the number of incidence, mortality, and DALYs in the global population, especially among the middle SDI quintile and the East Asia region. The BAPC results showed that ASDR, ASIR, and ASMR in women would increase but the male population remained relatively flat over the next 20 years. CONCLUSIONS: Although global efforts have been the most successful and effective in reducing the burden of EO-TBL cancer over the past three decades, there was strong regional and gender heterogeneity. EO-TBL cancer need more medical attention in the lower SDI quintiles and in the female population.

Ubiquitin-specific proteases: From biological functions to potential therapeutic applications in gastric cancer.

Deubiquitination, a post-translational modification regulated by deubiquitinases, is essential for cancer initiation and progression. Ubiquitin-specific proteases (USPs) are essential elements of the deubiquitinase family, and are overexpressed in gastric cancer (GC). Through the regulation of several signaling pathways, such as Wnt/ß-Catenin and nuclear factor-κB signaling, and the promotion of the expression of deubiquitination- and stabilization-associated proteins, USPs promote the proliferation, metastasis, invasion, and epithelial-mesenchymal transition of GC. In addition, the expression of USPs is closely related to clinicopathological features, patient prognosis, and chemotherapy resistance. USPs therefore could be used as prognostic biomarkers. USP targeting small molecule inhibitors have demonstrated strong anticancer activity. However, they have not yet been tested in the clinic. This article provides an overview of the latest fundamental research on USPs in GC, aiming to enhance the understanding of how USPs contribute to GC progression, and identifying possible targets for GC treatment to improve patient survival.

Applications of cryo-EM in drug development for STING.

STING is a critical adaptor protein in the cGAS-mediated DNA-sensing innate immune pathway. Binding of the second messenger cGAMP generated by cGAS to STING induces the high-order oligomerization and activation of the STING dimer. STING is a promising target for diseases associated with the cGAS/STING pathway such as cancer and autoimmune diseases. Recent applications of cryo-EM to STING have led to exciting progress in the understanding of its regulatory mechanism. Cryo-EM structures of STING bound to either cGAMP mimetics or novel small molecule ligands not only revealed the action mechanisms of these ligands but also suggested new ways to modulate the activity of STING for therapeutic purposes. Some of these recent studies are highlighted here.

Activation of human STING by a molecular glue-like compound.

Stimulator of interferon genes (STING) is a dimeric transmembrane adapter protein that plays a key role in the human innate immune response to infection and has been therapeutically exploited for its antitumor activity. The activation of STING requires its high-order oligomerization, which could be induced by binding of the endogenous ligand, cGAMP, to the cytosolic ligand-binding domain. Here we report the discovery through functional screens of a class of compounds, named NVS-STGs, that activate human STING. Our cryo-EM structures show that NVS-STG2 induces the high-order oligomerization of human STING by binding to a pocket between the transmembrane domains of the neighboring STING dimers, effectively acting as a molecular glue. Our functional assays showed that NVS-STG2 could elicit potent STING-mediated immune responses in cells and antitumor activities in animal models.

Endovenous Microwave Ablation Versus Radiofrequency Ablation for the Treatment of Lower Limb Varicose Veins.

BACKGROUND: This study aimed to retrospectively compare the clinical outcomes of endovenous microwave versus radiofrequency ablation combined with foam sclerotherapy in patients with lower limb varicose veins. METHODS: We identified patients with lower limb varicose veins treated with endovenous microwave ablation or radiofrequency ablation with foam sclerotherapy between January 2018 and June 2021 at our institution. Patients were followed-up for 12 months. Clinical results, including the pre-post-Aberdeen Varicose Vein Questionnaire and post-Aberdeen Varicose Vein Questionnaire and Venous Clinical Severity Score, were compared. Complications were documented and treated accordingly. RESULTS: We included 287 cases (295 limbs total; endovenous microwave ablation + foam sclerosing agent: n = 142, 146 limbs; radiofrequency ablation + foam sclerosing agent: n = 145, 149 limbs). The operative time was shorter for endovenous microwave ablation than radiofrequency ablation (42.58 ± 15.62 min vs. 65.46 ± 24.38 min, P < 0.05); however, other procedural parameters did not differ. Furthermore, hospitalization costs for endovenous microwave ablation were lower than those for radiofrequency ablation (21,063.74 ± 850.47 yuan vs. 23,312.40 ± 1,035.86 yuan, P < 0.05). At the 12-month follow-up, the great saphenous vein closure rate was similar in both groups (endovenous microwave ablation, 97% [142/146] vs. radiofrequency ablation, 98% [146/149]; P > 0.05). Additionally, the satisfaction or incidence rates of complications were not different among the groups. In both groups, the Aberdeen Varicose Vein Questionnaire and Venous Clinical Severity Score values were significantly lower 12 months postsurgery than before surgery; however, the postoperative values did not differ. CONCLUSIONS: Endovenous microwave ablation effectively treated lower limb varicose veins, with similar short-term effects as radiofrequency ablation. Moreover, it had a shorter operative time and was less expensive than endovenous radiofrequency ablation.

Efficacy and safety comparison of infrared laser moxibustion and traditional moxibustion in knee osteoarthritis: study protocol for a Zelen-design randomized controlled non-inferiority clinical trial.

BACKGROUND: Knee osteoarthritis (KOA) is the most common chronic degenerative joint disease and places a substantial burden on the public health resources in China. The purpose of this study is to preliminarily evaluate whether infrared laser moxibustion (ILM) is non-inferior to traditional moxibustion (TM) in the treatment of KOA. MATERIALS AND METHODS: In the designed Zelen-design randomized controlled non-inferiority clinical trial, a total of 74 patients with KOA will be randomly allocated to one of two interventions: ILM treatment or TM treatment. All participants will receive a 6-week treatment and a follow-up 4 weeks after treatment. The primary outcomes will be the mean change in pain scores on the numeric rating scale (NRS) measured at baseline and the end of last treatment at week 6. The secondary outcomes will be the pain scores on the NRS from weeks 1 to 5 after the start of treatment and the changes from baseline to endpoints (weeks 6 and 10) in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), SF-36, knee circumference, and 6-min walking test. In addition, safety assessment will be performed throughout the trial. CONCLUSION: The results of our study will help determine whether a 6-week treatment with ILM is non-inferior to TM in patients with KOA, therefore providing evidence to verify if ILM can become a safer alternative for TM in clinical applications in the future. TRIAL REGISTRATION: Clinical Trial Registration Platform (ChiCTR2200065264); Pre-results. Registered on 1 November 2022.

[Effectiveness of tofacitinib combined with iguratimod in the treatment of difficult-to-treat moderate-to-severe rheumatoid arthritis].

OBJECTIVE: To investigate the efficacy and safety of iguratimod combined with tofacitinib in patients with difficult-to-treat moderate-to-severe rheumatoid arthritis (RA). METHODS: In this prospective clinical study, 30 patients with difficult-to-treat moderate-to-severe RA who attended the Department of Rheumatology and Immunology of Shanxi Province Fenyang Hospital from September 2021 to June 2022 were selected. Twenty-three patients enrollment had been treated with 2 or more conventional synthetic disease modifying anti-rheumatic drugs (DMARDs) for more than 6 months. At least, methotrexate or leflunomide was included. Seven patients were treated with conventional synthetic DMARDs combined with tumor necrosis factor antagonists. Because all the patients had not reached the target of treatment, the combination treatment regimen of DMARDs was changed to iguratimod and tofacitinib. The observation period was 12 weeks. Clinical data were collected before and after treatment. At the end of 4 weeks, 8 weeks and 12 weeks, the clinical data were collected such as swollen joints count (SJC), tender joints count (TJC), time of morning stiffness, clinical disease activity index (CDAI), health status assessment questionnaire (HAQ), and 28-joint disease activity score (DAS28) were included. We collected laboratory indicators, recorded the patient's medication, and observed some changes to see if any adverse drug reactions occurred during the treatment. RESULTS: There were significant differences in erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), platelet (PLT), SJC, TJC, DAS28 based on ESR(DAS28-ESR), time of morning stiffness, HAQ, CDAI, and anti-cyclic citrullinated peptide antibody before and after treatment. The differences had statistical significance (P < 0.05). There was no statistical differences in globulin before and after treatment (P>0.05). During the treatment of iguratimod combined with tofacitinib, there was no serious adverse reactions such as leukopenia, significant elevation of liver enzymes, allergy or thromboemblolic events that occurred in all the patients. CONCLUSION: Iguratimod combined with tofacitinib in the treatment of difficult-to-treat moderate-to-severe RA may have efficacy. The machanism was improving the patients' recent clinical symptoms by reducing inflammatory indexes. This combination treatment regimen with iguratimod and tofacitinib has a good safety profile.

Chiral charge density wave induced by mirror symmetry breaking in kagome metal.

Kagome lattice provides a distinctive platform to investigate various correlated electron orders. Recently, an unconventional charge density wave (CDW) with novel chirality is observed in the kagome metalAV3Sb5(A= K, Rb, Cs), and the origin of which is still unclear. Here, using a tight-binding model and the mean-field method, we calculate the electron order in the quasi-two-dimensional kagome lattice with 1/3 electron filling, and show that the chiral CDW emerges under a set of parameters withC6rotational symmetry but without mirror symmetry. Physically, the reason why we choose this set of parameters is based on the possible tangential distortion of the kagome lattice. Our results provide a fresh insight to understand the microscopic origin of the unconventional CDW inAV3Sb5.

Development of a Nomogram to Predict Postoperative Peritoneal Metastasis of Colon Cancer.

OBJECTIVE: The aim of this study was to determine the clinicopathological and radiological risk factors for postoperative peritoneal metastasis and develop a prediction model for the early detection of peritoneal metastasis in patients with colon cancer. METHODS: We included 174 patients with colon cancer. The clinicopathological and radiological data were retrospectively analyzed. A Cox proportional hazards regression model was used to identify risk factors for postoperative peritoneal metastasis. Based on these risk factors, a nomogram was developed. RESULTS: At a median follow-up of 63 months, 43 (24.7%) patients developed peritoneal metastasis. Six independent risk factors (hazards ratio [95% confidence interval]) were identified for postoperative peritoneal metastasis: abdominopelvic fluid (2.12 [1.02-4.40]; P = 0.04), longer maximum tumor length (1.02 [1.00-1.03]; P = 0.02), pN1 (2.50 [1.13-5.56]; P = 0.02), pN2 (4.45 [1.77-11.17]; P = 0.02), nonadenocarcinoma (2.75 [1.18-6.38]; P = 0.02), and preoperative carcinoembryonic antigen levels ≥5 ng/mL (3.08 [1.50-6.30]; P < 0.01). A clinicopathological-radiological model was developed based on these factors. The model showed good discrimination (concordance index, 0.798 [0.723-0.876]; P < 0.001) and was well-calibrated. CONCLUSIONS: The developed clinicopathological-radiological nomogram may assist clinicians in identifying patients at high risk of postoperative peritoneal metastasis.

Quassinoids from Twigs of Harrisonia perforata (Blanco) Merr and Their Anti-Parkinson's Disease Effect.

Six new C-20 and one new C-19 quassinoids, named perforalactones F-L (1-7), were isolated from twigs of Harrisonia perforata. Spectroscopic and X-ray crystallographic experiments were conducted to identify their structures. Through oxidative degradation of perforalactone B to perforaqussin A, the biogenetic process from C-25 quassinoid to C-20 via Baeyer-Villiger oxidation was proposed. Furthermore, the study evaluated the anti-Parkinson's disease potential of these C-20 quassinoids for the first time on 6-OHDA-induced PC12 cells and a Drosophila Parkinson's disease model of PINK1B9. Perforalactones G and I (2 and 4) showed a 10-15% increase in cell viability of the model cells at 50 µM, while compounds 2 and 4 (100 µM) significantly improved the climbing ability of PINK1B9 flies and increased the dopamine level in the brains and ATP content in the thoraces of the flies.

The Composition and Diversity of the Rhizosphere Bacterial Community of Ammodendron bifolium Growing in the Takeermohuer Desert Are Different from Those in the Nonrhizosphere.

Soil microorganisms play important roles in vegetation establishment and soil biogeochemical cycling. Ammodendron bifolium is a dominant sand-fixing (i.e., stabilizing sand dunes) and endangered plant in the Takeermohuer Desert, and the bacterial community associated with this plant rhizosphere is still unclear. In this study, we investigated the composition and diversity of the bacterial community from the A. bifolium rhizosphere and bulk soil at different soil depths (i.e., 0-40 cm, 40-80 cm, 80-120 cm) using culture and high-throughput sequencing methods. We preliminarily analyzed the edaphic factors influencing the structure of bacterial communities. The results showed that the high-salinity Takeermohuer Desert has an oligotrophic environment, while the A. bifolium rhizosphere exhibited a relatively nutrient-rich environment due to higher contents of soil organic matter (SOM) and soil alkaline nitrogen (SAN) than bulk soil. The dominant bacterial groups in the desert were Actinobacteria (39.8%), Proteobacteria (17.4%), Acidobacteria (10.2%), Bacteroidetes (6.3%), Firmicutes (6.3%), Chloroflexi (5.6%), and Planctomycetes (5.0%) at the phylum level. However, the relative abundances of Proteobacteria (20.2%) and Planctomycetes (6.1%) were higher in the rhizosphere, and those of Firmicutes (9.8%) and Chloroflexi (6.9%) were relatively higher in barren bulk soil. A large number of Actinobacteria were detected in all soil samples, of which the most abundant genera were Streptomyces (5.4%) and Actinomadura (8.2%) in the bulk soil and rhizosphere, respectively. The Chao1 and PD_whole_tree indices in the rhizosphere soil were significantly higher than those in the bulk soil at the same soil depth and tended to decrease with increasing soil depth. Co-occurrence network analyses showed that the keystone species in the Takeermohuer Desert were the phyla Actinobacteria, Acidobacteria, Proteobacteria, and Chloroflexi. Furthermore, the major edaphic factors affecting the rhizosphere bacterial community were electrical conductivity (EC), SOM, soil total nitrogen (STN), SAN, and soil available potassium (SAK), while the major edaphic factors affecting the bacterial community in bulk soil were distance and ratio of carbon to nitrogen (C/N). We concluded that the A. bifolium rhizosphere bacterial community is different from that of the nonrhizosphere in composition, structure, diversity, and driving factors, which may improve our understanding of the relationship between plant and bacterial communities and lay a theoretical foundation for A. bifolium species conservation in desert ecosystems.