Short-chain fatty acids mitigate Methamphetamine-induced hepatic injuries in a Sigma-1 receptor-dependent manner.

Methamphetamine (Meth) is a potent psychostimulant with well-established hepatotoxicity. Gut microbiota-derived short-chain fatty acids (SCFAs) have been reported to yield beneficial effects on the liver. In this study, we aim to further reveal the mechanisms of Meth-induced hepatic injuries and investigate the potential protective effects of SCFAs. Herein, mice were intraperitoneally injected with 15 mg/kg Meth to induce hepatic injuries. The composition of fecal microbiota and SCFAs was profiled using 16 S rRNA sequencing and Gas Chromatography/Mass Spectrometry (GC/MS) analysis, respectively. Subsequently, SCFAs supplementation was performed to evaluate the protective effects against hepatic injuries. Additionally, Sigma-1 receptor knockout (S1R-/-) mice and fluvoxamine (Flu), an agonist of S1R, were introduced to investigate the mechanisms underlying the protective effects of SCFAs. Our results showed that Meth activated S1R and induced hepatic autophagy, inflammation, and oxidative stress by stimulating the MAPK/ERK pathway. Meanwhile, Meth disrupted SCFAs product-related microbiota, leading to a reduction in fecal SCFAs (especially Acetic acid and Propanoic acid). Accompanied by the optimization of gut microbiota, SCFAs supplementation normalized S1R expression and ameliorated Meth-induced hepatic injuries by repressing the MAPK/ERK pathway. Effectively, S1R knockout repressed Meth-induced activation of the MAPK/ERK pathway and further ameliorated hepatic injuries. Finally, the overexpression of S1R stimulated the MAPK/ERK pathway and yielded comparable adverse phenotypes to Meth administration. These findings suggest that Meth-induced hepatic injuries relied on the activation of S1R, which could be alleviated by SCFAs supplementation. Our study confirms the crucial role of S1R in Meth-induced hepatic injuries for the first time and provides a potential preemptive therapy.

Efficacy of simple and very brief handgrip and isometric exercises for reducing withdrawal symptoms in cigarette smokers: A pilot randomized controlled trial.

INTRODUCTION: Withdrawal symptoms lead to smoking relapse and reduce the intention to quit. The present pilot RCT examined the effect of simple and very brief handgrip and isometric exercises on reducing withdrawal symptoms, measured by the strength of tobacco craving, Questionnaire of Smoking Urges-Brief (QSU-B), Mood and Physical Symptoms Scale (MPSS), and Positive and Negative Affect Schedule (PANAS). METHODS: In this 2-arm, open-labeled pilot RCT, 30 current smokers who had abstained from tobacco for at least 9 hours were randomly assigned (allocation ratio 1:1) to either the intervention group that watched a 5-minute video and did 5-minute handgrip and isometric exercises (pulling and pushing) or control group that watched 10-minute healthy-diet videos. Measurements were taken before, immediately after, and 10 minutes post-intervention. Outcomes were self-reported strength of tobacco craving, QSU-B, MPSS, and PANAS scores. The effect size for group-by-time interaction was assessed using Cohen's f2 (small=0.02, medium=0.15, large=0.35). RESULTS: Group-by-time interactions showed that the intervention group showed larger reductions than the control group in the strength of tobacco craving (Cohen's f2=0.54, 95% CI: 0.52-0.57), QSU-B (Cohen's f2=0.77; 95% CI: 0.74-0.80), and MPSS (Cohen's f2=0.51; 95% CI: 0.46-0.56) over the three measurement points. CONCLUSIONS: This RCT showed that simple and brief handgrip and isometric exercises could immediately reduce withdrawal symptoms and up to 10 minutes. CLINICAL TRIAL REGISTRATION: in https://clinicaltrials.gov/. IDENTIFIER: NCT04059497.

Polystyrene nanoplastics exacerbate aflatoxin B1-induced hepatic injuries by modulating the gut-liver axis.

Dietary pollution of Aflatoxin B1 (AFB1) poses a great threat to global food safety, which can result in serious hepatic injuries. Following the widespread use of plastic tableware, co-exposure to microplastics and AFB1 has dramatically increased. However, whether microplastics could exert synergistic effects with AFB1 and amplify its hepatotoxicity, and the underlying mechanisms are still unelucidated. Here, mice were orally exposed to 100 nm polystyrene nanoplastics (NPs) and AFB1 to investigate the influences of NPs on AFB1-induced hepatic injuries. We found that exposure to only NPs or AFB1 resulted in colonic inflammation and the impairment of the intestinal barrier, which was exacerbated by combined exposure to NPs and AFB1. Meanwhile, co-exposure to NPs exacerbated AFB1-induced dysbiosis of gut microbiota and remodeling of the fecal metabolome. Moreover, NPs and AFB1 co-exposure exhibited higher levels of systemic inflammatory factors compared to AFB1 exposure. Additionally, NPs co-exposure further exacerbated AFB1-induced hepatic fibrosis and inflammation, which could be associated with the overactivation of the TLR4/MyD88/NF-κB pathway. Notably, Spearman's correlation analysis revealed that the exacerbation of NPs co-exposure was closely associated with microbial dysbiosis. Furthermore, microbiota from NPs-exposed mice (NPsFMT) partly reproduced the exacerbation of NPs on AFB1-induced systemic and hepatic inflammation, but not fibrosis. In summary, our findings indicate that gut microbiota could be involved in the exacerbation of NPs on AFB1-induced hepatic injuries, highlighting the health risks of NPs.

Effectiveness of Very Brief Advice on Tobacco Cessation: A Systematic Review and Meta-Analysis.

BACKGROUND: Very brief advice (VBA; ≤ 3 min) on quitting is practical and scalable during brief medical interactions with patients who smoke. This study aims to synthesize the effectiveness of VBA for smoking cessation and summarize the implementation strategies. METHODS: We searched randomized controlled trials aiming at tobacco abstinence and comparing VBA versus no smoking advice or no contact from Medline, Embase, CINAHL, Cochrane Library, PsycInfo databases, six Chinese databases, two trial registries ClinicalTrials.gov and WHO-ICTRP from inception to September 30, 2023. Grading of Recommendations, Assessment, Development, and Evaluations framework was used to assess the certainty of the evidence of the meta-analytic findings. The outcomes were self-reported long-term tobacco abstinence at least 6 months after treatment initiation, earlier than 6 months after treatment initiation, and quit attempts. Effect sizes were computed as risk ratio (RR) with 95% CI using frequentist random-effect models. DATA SYNTHESIS: Thirteen randomized controlled trials from 15 articles (n = 26,437) were included. There was moderate-certainty evidence that VBA significantly increased self-reported tobacco abstinence at ≥ 6 months in the adjusted model (adjusted risk ratio ARR 1.17, 95% CI: 1.07-1.27) compared with controls. The sensitivity analysis showed similar results when abstinence was verified by biochemical validation (n = 6 studies, RR 1.53, 95% CI 0.98-2.40). There was high-certainty evidence that VBA significantly increased abstinence at < 6 months (ARR 1.22, 95% CI: 1.01-1.47). Evidence of effect on quit attempts (ARR 1.03, 95% CI 0.97-1.08) was of very low certainty. DISCUSSION: VBA delivered in a clinical setting is effective in increasing self-reported tobacco abstinence, which provides support for wider adoption in clinical practice.

Deficiency of the HGF/Met pathway leads to thyroid dysgenesis by impeding late thyroid expansion.

The mechanisms of bifurcation, a key step in thyroid development, are largely unknown. Here we find three zebrafish lines from a forward genetic screening with similar thyroid dysgenesis phenotypes and identify a stop-gain mutation in hgfa and two missense mutations in met by positional cloning from these zebrafish lines. The elongation of the thyroid primordium along the pharyngeal midline was dramatically disrupted in these zebrafish lines carrying a mutation in hgfa or met. Further studies show that MAPK inhibitor U0126 could mimic thyroid dysgenesis in zebrafish, and the phenotypes are rescued by overexpression of constitutively active MEK or Snail, downstream molecules of the HGF/Met pathway, in thyrocytes. Moreover, HGF promotes thyrocyte migration, which is probably mediated by downregulation of E-cadherin expression. The delayed bifurcation of the thyroid primordium is also observed in thyroid-specific Met knockout mice. Together, our findings reveal that HGF/Met is indispensable for the bifurcation of the thyroid primordium during thyroid development mediated by downregulation of E-cadherin in thyrocytes via MAPK-snail pathway.

The effects of flow settings during high-flow nasal cannula oxygen therapy for neonates and young children.

BACKGROUND: During neonatal and paediatric high-flow nasal cannula therapy, optimising the flow setting is crucial for favourable physiological and clinical outcomes. However, considerable variability exists in clinical practice regarding initial flows and subsequent adjustments for these patients. Our review aimed to summarise the impact of various flows during high-flow nasal cannula treatment in neonates and children. METHODS: Two investigators independently searched PubMed, Embase, Web of Science, Scopus and Cochrane for in vitro and in vivo studies published in English before 30 April 2023. Studies enrolling adults (≥18 years) or those using a single flow setting were excluded. Data extraction and risk of bias assessments were performed independently by two investigators. The study protocol was prospectively registered with PROSPERO (CRD42022345419). RESULTS: 38 406 studies were identified, with 44 included. In vitro studies explored flow settings' effects on airway pressures, humidity and carbon dioxide clearance; all were flow-dependent. Observational clinical studies consistently reported that higher flows led to increased pharyngeal pressure and potentially increased intrathoracic airway pressure (especially among neonates), improved oxygenation, and reduced respiratory rate and work of breathing up to a certain threshold. Three randomised controlled trials found no significant differences in treatment failure among different flow settings. Flow impacts exhibited significant heterogeneity among different patients. CONCLUSION: Individualising flow settings in neonates and young children requires consideration of the patient's peak inspiratory flow, respiratory rate, heart rate, tolerance, work of breathing and lung aeration for optimal care.

Dual-Region Computed Tomography Radiomics-Based Machine Learning Predicts Subcarinal Lymph Node Metastasis in Patients with Non-small Cell Lung Cancer.

BACKGROUND: Noninvasively and accurately predicting subcarinal lymph node metastasis (SLNM) for patients with non-small cell lung cancer (NSCLC) remains challenging. This study was designed to develop and validate a tumor and subcarinal lymph nodes (tumor-SLNs) dual-region computed tomography (CT) radiomics model for predicting SLNM in NSCLC. METHODS: This retrospective study included NSCLC patients who underwent lung resection and SLNs dissection between January 2017 and December 2020. The radiomic features of the tumor and SLNs were extracted from preoperative CT, respectively. Ninety machine learning (ML) models were developed based on tumor region, SLNs region, and tumor-SLNs dual-region. The model performance was assessed by the area under the curve (AUC) and validated internally by fivefold cross-validation. RESULTS: In total, 202 patients were included in this study. ML models based on dual-region radiomics showed good performance for SLNM prediction, with a median AUC of 0.794 (range, 0.686-0.880), which was superior to those of models based on tumor region (median AUC, 0.746; range, 0.630-0.811) and SLNs region (median AUC, 0.700; range, 0.610-0.842). The ML model, which is developed by using the naive Bayes algorithm and dual-region features, had the highest AUC of 0.880 (range of cross-validation, 0.825-0.937) among all ML models. The optimal logistic regression model was inferior to the optimal ML model for predicting SLNM, with an AUC of 0.727. CONCLUSIONS: The CT radiomics showed the potential for accurately predicting SLNM in NSCLC patients. The ML model with dual-region radiomic features has better performance than the logistic regression or single-region models.

High-throughput mutagenesis and screening approach for the identification of drug-resistant mutations in the rifampicin resistance-determining region of mycobacteria.

Rifampicin is the most powerful first-line antibiotic for tuberculosis, which is caused by Mycobacterium tuberculosis. Although accumulating evidence from sequencing data of clinical M. tuberculosis isolates suggested that mutations in the rifampicin-resistance-determining region (RRDR) are strongly associated with rifampicin resistance, the comprehensive characterisation of RRDR polymorphisms that confer this resistance remains challenging. By incorporating I-SceI sites for I-SceI-based integrant removal and utilizing an L5 swap strategy, we efficiently replaced the integrated plasmid with alternative alleles, making mass allelic exchange feasible in mycobacteria. Using this method to establish a fitness-related gain-of function screen, we generated a mutant library that included all single-amino-acid mutations in the RRDR, and identified the important positions corresponding to some well-known rifampicin-resistance mutations (Q513, D516, S522, H525, R529, S531). We also detected a novel two-point mutation located in the RRDR confers a fitness advantage to M. smegmatis in the presence or absence of rifampicin. Our method provides a comprehensive insight into the growth phenotypes of RRDR mutants and should facilitate the development of anti-tuberculosis drugs.

Curriculum vitae of CUG binding protein 1 (CELF1) in homeostasis and diseases: a systematic review.

RNA-binding proteins (RBPs) are kinds of proteins with either singular or multiple RNA-binding domains (RBDs), and they can assembly into ribonucleic acid-protein complexes, which mediate transportation, editing, splicing, stabilization, translational efficiency, or epigenetic modifications of their binding RNA partners, and thereby modulate various physiological and pathological processes. CUG-BP, Elav-like family 1 (CELF1) is a member of the CELF family of RBPs with high affinity to the GU-rich elements in mRNA, and thus exerting control over critical processes including mRNA splicing, translation, and decay. Mounting studies support that CELF1 is correlated with occurrence, genesis and development and represents a potential therapeutical target for these malignant diseases. Herein, we present the structure and function of CELF1, outline its role and regulatory mechanisms in varieties of homeostasis and diseases, summarize the identified CELF1 regulators and their structure-activity relationships, and prospect the current challenges and their solutions during studies on CELF1 functions and corresponding drug discovery, which will facilitate the establishment of a targeted regulatory network for CELF1 in diseases and advance CELF1 as a potential drug target for disease therapy.

Reconfigurable Microlens Array Enables Tunable Imaging Based on Shape Memory Polymers.

Microlens arrays (MLAs) with a tunable imaging ability are core components of advanced micro-optical systems. Nevertheless, tunable MLAs generally suffer from high power consumption, an undeformable rigid body, large and complex systems, or limited focal length tunability. The combination of reconfigurable smart materials with MLAs may lead to distinct advantages including programmable deformation, remote manipulation, and multimodal tunability. However, unlike photopolymers that permit flexible structuring, the fabrication of tunable MLAs and compound eyes (CEs) based on transparent smart materials is still rare. In this work, we report reconfigurable MLAs that enable tunable imaging based on shape memory polymers (SMPs). The smart MLAs with closely packed 200 × 200 microlenses (40.0 µm in size) are fabricated via a combined technology that involves wet etching-assisted femtosecond laser direct writing of MLA templates on quartz, soft lithography for MLA duplication using SMPs, and the mechanical heat setting for programmable reconfiguration. By stretching or squeezing the shape memory MLAs at the transition temperature (80 °C), the size, profiles, and spatial distributions of the microlenses can be programmed. When the MLA is stretched from 0 to 120% (area ratio), the focal length is increased from 116 to 283 µm. As a proof of concept, reconfigurable MLAs and a 3D CE with a tunable field of view (FOV, 160-0°) have been demonstrated in which the thermally triggered shape memory deformation has been employed for tunable imaging. The reconfigurable MLAs and CEs with a tunable focal length and adjustable FOV may hold great promise for developing smart micro-optical systems.

Highly efficient capture approach for the identification of diverse inherited retinal disorders.

Our study presents a 319-gene panel targeting inherited retinal dystrophy (IRD) genes. Through a multi-center retrospective cohort study, we validated the assay's effectiveness and clinical utility and characterized the mutation spectrum of Taiwanese IRD patients. Between January 2018 and May 2022, 493 patients in 425 unrelated families, all initially suspected of having IRD without prior genetic diagnoses, underwent detailed ophthalmic and physical examinations (with extra-ocular features recorded) and genetic testing with our customized panel. Disease-causing variants were identified by segregation analysis and clinical interpretation, with validation via Sanger sequencing. We achieved a read depth of >200× for 94.2% of the targeted 1.2 Mb region. 68.5% (291/425) of the probands received molecular diagnoses, with 53.9% (229/425) resolved cases. Retinitis pigmentosa (RP) is the most prevalent initial clinical impression (64.2%), and 90.8% of the cohort have the five most prevalent phenotypes (RP, cone-rod syndrome, Usher's syndrome, Leber's congenital amaurosis, Bietti crystalline dystrophy). The most commonly mutated genes of probands that received molecular diagnosis are USH2A (13.7% of the cohort), EYS (11.3%), CYP4V2 (4.8%), ABCA4 (4.5%), RPGR (3.4%), and RP1 (3.1%), collectively accounted for 40.8% of diagnoses. We identify 87 unique unreported variants previously not associated with IRD and refine clinical diagnoses for 21 patients (7.22% of positive cases). We developed a customized gene panel and tested it on the largest Taiwanese cohort, showing that it provides excellent coverage for diverse IRD phenotypes.

Expression and regulation of HIF-1a in hypoxic pulmonary hypertension: Focus on pathological mechanism and Pharmacological Treatment.

Hypoxia inducible factor-1(HIF-1), a heterodimeric transcription factor, is composed of two subunits (HIF-1α and HIF-1ß). It is considered as an important transcription factor for regulating oxygen changes in hypoxic environment, which can regulate the expression of various hypoxia-related target genes and play a role in acute and chronic hypoxia pulmonary vascular reactions. In this paper, the function and mechanism of HIF-1a expression and regulation in hypoxic pulmonary hypertension (HPH) were reviewed, and current candidate schemes for treating pulmonary hypertension by using HIF-1a as the target were introduced, so as to provide reference for studying the pathogenesis of HPH and screening effective treatment methods.

Heterogeneity in familial clustering of metabolic syndrome components in the multiethnic GENNID study.

OBJECTIVE: Metabolic syndrome (MetS) is defined by clustering of cardiometabolic components, which may be present in different combinations. The authors evaluated clustering in individuals and extended families within and across ancestry groups. METHODS: The prevalence of different combinations of MetS components (high fasting glucose, low high-density lipoprotein cholesterol, high triglycerides, high blood pressure, and abdominal obesity) was estimated in 1651 individuals (340 families) self-reporting as European American (EA), Hispanic/Mexican American (MA), African American (AA), and Japanese American (JA). Odds ratios were estimated using logistic regression with generalized estimating equations comparing individual MetS components, number, and combinations of components for each ancestry group versus EA. RESULTS: Clustering of all five components (Combination #16) was more prevalent in EA (29.9%) and MA (25.2%) individuals than in AA (18.7%) and JA (15.5%) individuals. Compared with EA individuals, AA individuals were 64% and 66% less likely to have high triglycerides and low high-density lipoprotein cholesterol, whereas JA individuals were 85% and 56% less likely to have abdominal obesity and high blood pressure, respectively. Compared with EA individuals, the odds of having two, four, or five components were at least 77% lower in JA individuals, whereas the odds of having three, four, or five components were at least 3.79 times greater in MA individuals. CONCLUSIONS: Understanding heterogeneity in MetS clustering may identify factors important in reducing health disparities.

Generalized Characteristic Function Loss for Crowd Analysis in the Frequency Domain.

Typical approaches that learn crowd density maps are limited to extracting the supervisory information from the loosely organized spatial information in the crowd dot/density maps. This paper tackles this challenge by performing the supervision in the frequency domain. More specifically, we devise a new loss function for crowd analysis called generalized characteristic function loss (GCFL). This loss carries out two steps: 1) transforming the spatial information in density or dot maps to the frequency domain; 2) calculating a loss value between their frequency contents. For step 1, we establish a series of theoretical fundaments by extending the definition of the characteristic function for probability distributions to density maps, as well as proving some vital properties of the extended characteristic function. After taking the characteristic function of the density map, its information in the frequency domain is well-organized and hierarchically distributed, while in the spatial domain it is loose-organized and dispersed everywhere. In step 2, we design a loss function that can fit the information organization in the frequency domain, allowing the exploitation of the well-organized frequency information for the supervision of crowd analysis tasks. The loss function can be adapted to various crowd analysis tasks through the specification of its window functions. In this paper, we demonstrate its power in three tasks: Crowd Counting, Crowd Localization and Noisy Crowd Counting. We show the advantages of our GCFL compared to other SOTA losses and its competitiveness to other SOTA methods by theoretical analysis and empirical results on benchmark datasets. Our codes are available at https://github.com/wbshu/Crowd_Counting_in_the_Frequency_Domain.

Acute severe hypoglycemia immediately after induction of anesthesia in an elderly patient with type 2 diabetes mellitus: A case report.

RATIONALE: Acute severe hypoglycemia immediately following anesthesia induction is a rare but life-threatening complication that is frequently underdiagnosed due to insufficient awareness. Among the various physiological processes influenced by opioids, alterations in blood glucose levels induced by opioids are a side effect that is commonly overlooked. The significance of this report lies in emphasizing the neglected association between opioids and hypoglycemia and highlighting the importance of close glucose monitoring to prevent hypoglycemic events in the perioperative setting. PATIENT CONCERNS: An 89-year-old man with type 2 diabetes mellitus experienced acute severe hypoglycemic episode immediately after general anesthesia induction. Baseline blood glucose level before starting anesthesia induction was 4.0 mmol/L. However, it decreased substantially to 0.96 mmol/L immediately after anesthesia induction. DIAGNOSIS: The patient exhibited normal serum insulin, C-peptide, and cortisol levels, alongside unremarkable renal and hepatic function. After excluding other causes of hypoglycemia, we speculate that opioids were the culprits due to the temporal association and the rapid decline in blood glucose levels. INTERVENTIONS: Forty milliliters of 50% dextrose were administered intravenously followed by an infusion of 5% dextrose. OUTCOMES: Recovery from anesthesia, extubation, and postoperative recovery were unremarkable. No further hypoglycemic episodes occurred during hospitalization. LESSONS: A precipitous and rapid decline in blood glucose following anesthesia induction is extremely uncommon. When a clinical anesthesiologist detects an abnormally low bispectral index during general anesthesia, hypoglycemia should be suspected. Instituting glucose monitoring in these situations can enable a timely diagnosis, forestalling the onset of life-threatening severe hypoglycemia.

Physically cross-linked organo-hydrogels for friction interfaces in joint replacements: design, evaluation and potential clinical applications.

This paper investigates physically crosslinked organo-hydrogels for total hip replacement surgery. Current materials in artificial joints have limitations in mechanical performance and biocompatibility. To overcome these issues, a new approach based on hydrogen bonds between polyvinyl alcohol, poly(2-hydroxyethyl methacrylate), and glycerin is proposed to develop bioactive organo-hydrogels with improved mechanical properties and biocompatibility. This study analyzes local pathological characteristics, systemic toxicity, and mechanical properties of the gels. The results show that the gels possess excellent biocompatibility and mechanical strength, suggesting their potential as an alternative material for total hip replacement surgery. These findings contribute to improving patient outcomes in joint replacement procedures.

Albumin-to-fibrinogen ratio is an independent prognostic parameter in de novo non-M3 acute myeloid leukemia.

Inflammation and nutrition related proteins participate in the development of acute myeloid leukemia (AML). It has been reported that the albumin-to-fibrinogen ratio (AFR) could serve as a prognostic indicator in patients with malignancy, but the precise relevance of AML is unclear. This study aimed to evaluate the effect of AFR on survival prognosis in patients with AML. We analyzed 227 patients newly diagnosed with non-M3 AML. AFR was calculated as albumin divided by fibrinogen. Based on the cutoff point from X-tile program, patients were divided into AFR-high (38.8%) and AFR-low (61.2%) groups. AFR-low group showed a poorer complete remission rate (P < 0.001) and median time to relapse (P = 0.026), while the mortality was higher (P = 0.009) than AFR-high ones. According to the log-rank test, AFR-low group had shorter OS (P < 0.001) and DFS (P = 0.034). Multivariate analysis identified AFR, ELN risk, bone marrow transplant, and hemoglobin as independent prognostic variables associated with OS. A visualized nomogram for predicting OS was performed. The C-index (0.75), calibration plots, and decision curve analyses of new model showed better discrimination, calibration, and net benefits than the ELN risk model. The time-dependent receiver operating characteristic (ROC) curve of 1-, 2-, and 3-year also functioned well (AUC, 0.81, 0.93 and 0.90, respectively). Our study provided a comprehensive view of AFR which could be an independent prognostic indicator in AML patients. The prognostic model utilized readily available information from ordinary clinical practice to improve predictive performance, identify risks, and assist in therapeutic decision-making.

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.