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There are numerous species in the Erwiniaceae family that are important for agricultural and clinical purposes. Here we described the Erwiniaceae bacterium PD-1 isolated from mushroom (Pleurotus eryngii) compost. Comparative genomic and phylogenetic analyses showed that the strain PD-1 was assigned to a new genus and species, Paramixta manurensis gen. nov., sp. nov. in the family Erwiniaceae. From the average amino acid index, we identified the five AroBEKAC proteins in the shikimate pathway as a minimal set of molecular markers to reconstruct the phylogenetic tree of the Erwiniaceae species. The strain PD-1 containing annotated genes for ubiquinone and menaquinone produced a higher level of ubiquinone (Q8) than demethylmenaquinone (DMK8) and menaquinone (MK8) in anaerobic condition compared to aerobic condition, as similarly did the reference strains from the genera Mixta and Erwinia. Results from fatty acid methyl ester and numerical analyses of strain PD-1 showed a similarity to species of the genera Mixta and Winslowiella. This study revealed that the strain's ability to utilize polyols, such as glycerol, erythritol, and D-arabitol, distinguished the strain PD-1 from the nearest relative and other type strains. The analyzed genetic markers and biochemical properties of the strain PD-1 suggest its potential role in the process of mushroom compost through the degradation of carbohydrates and polysaccharides derived from fungi and plants. Additionally, it can produce a high concentration of indole-3-acetic acid as a plant growth-promoting agent.
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Agaricales , Ácidos Indolacéticos , Filogenia , Agaricales/genética , Agaricales/metabolismo , Agaricales/clasificación , Ácidos Indolacéticos/metabolismo , Compostaje , Microbiología del Suelo , ARN Ribosómico 16S/genéticaRESUMEN
Methylation of proteins and nucleic acids plays a fundamental role in epigenetic regulation, and discovery of methyltransferase (MT) inhibitors is an area of intense activity. Because of the diversity of MTs and their products, assay methods that detect S-adenosylhomocysteine (SAH) - the invariant product of S-adenosylmethionine (SAM)-dependent methylation reactions - offer some advantages over methods that detect specific methylation events. However, direct, homogenous detection of SAH requires a reagent capable of discriminating between SAH and SAM, which differ by a single methyl group. Moreover, MTs are slow enzymes and many have submicromolar affinities for SAM; these properties translate to a need for detection of SAH at low nanomolar concentrations in the presence of excess SAM. To meet these needs, we leveraged the exquisite molecular recognition properties of a naturally occurring SAH-sensing RNA aptamer, or riboswitch. By splitting the riboswitch into two fragments, such that SAH binding induces assembly of a trimeric complex, we engineered sensors that transduce binding of SAH into positive fluorescence polarization (FP) and time resolved Förster resonance energy transfer (TR-FRET) signals. The split riboswitch configuration, called the AptaFluor™ SAH Methyltransferase Assay, allows robust detection of SAH (Z' > 0.7) at concentrations below 10 nM, with overnight signal stability in the presence of typical MT assay components. The AptaFluor assay tolerates diverse MT substrates, including histones, nucleosomes, DNA and RNA, and we demonstrated its utility as a robust, enzymatic assay method for several methyltransferases with SAM Km values < 1 µM. The assay was validated for HTS by performing a pilot screen of 1,280 compounds against the SARS-CoV-2 RNA capping enzyme, nsp14. By enabling direct, homogenous detection of SAH at low nanomolar concentrations, the AptaFluor assay provides a universal platform for screening and profiling MTs at physiologically relevant SAM concentrations.
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Pruebas de Enzimas , Metiltransferasas , Riboswitch , S-Adenosilhomocisteína , S-Adenosilmetionina , S-Adenosilhomocisteína/metabolismo , Riboswitch/genética , Metiltransferasas/metabolismo , Metiltransferasas/genética , Pruebas de Enzimas/métodos , S-Adenosilmetionina/metabolismo , Transferencia Resonante de Energía de Fluorescencia/métodos , Metilación , Humanos , Polarización de Fluorescencia/métodos , Aptámeros de Nucleótidos/química , Aptámeros de Nucleótidos/genéticaRESUMEN
T cell acute lymphoblastic leukemia (T-ALL) is an aggressive immature T cell cancer. Mutations in IL7R have been analyzed genetically, but downstream effector functions such as STAT5A and STAT5B hyperactivation are poorly understood. Here, we studied the most frequent and clinically challenging STAT5BN642H driver in T cell development and immature T cell cancer onset and compared it with STAT5A hyperactive variants in transgenic mice. Enhanced STAT5 activity caused disrupted T cell development and promoted an early T cell progenitor-ALL phenotype, with upregulation of genes involved in T cell receptor (TCR) signaling, even in absence of surface TCR. Importantly, TCR pathway genes were overexpressed in human T-ALL and mature T cell cancers and activation of TCR pathway kinases was STAT5 dependent. We confirmed STAT5 binding to these genes using ChIP-Seq analysis in human T-ALL cells, which were sensitive to pharmacologic inhibition by dual STAT3/5 degraders or ZAP70 tyrosine kinase blockers in vitro and in vivo. We provide genetic and biochemical proof that STAT5A and STAT5B hyperactivation can initiate T-ALL through TCR pathway hijacking and suggest similar mechanisms for other T cell cancers. Thus, STAT5 or TCR component blockade are targeted therapy options, particularly in patients with chemoresistant clones carrying STAT5BN642H.
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Leucemia-Linfoma Linfoblástico de Células T Precursoras , Animales , Humanos , Ratones , Ratones Transgénicos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Proteínas Tirosina Quinasas , Receptores de Antígenos de Linfocitos T/genética , Transducción de Señal , Factor de Transcripción STAT5/genéticaRESUMEN
Very late stent thrombosis (VLST) refers to stent thrombosis occurring beyond one year after coronary intervention. "Very" very or extremely late stent thrombosis (VVLST), occurring after five years of drug-eluting stent (DES) implantation, is extremely rare. We report a case of a 60-year-old male patient with ST-elevation myocardial infarction (STEMI) due to in-stent thrombosis 12.3 years after first-generation DES implantation; we also engage in a brief discussion of its pathogenesis and prevention.
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According to a review of numerous publications and scientific reports, the effects of urbanization on urban climate are of greatest concern. This study aims to evaluate the impact of urbanization focusing on population growth on precipitation trends in 11 provinces across Vietnam during the period 2008-2018 by identifying the relationship between population growth and precipitation change. Regression analysis is used to determine the trends of precipitation and population growth. Precipitation maps and graphs show the overall precipitation trends, changes, and patterns in past decades. Overall, population growth tends to correlate with precipitation change trends. Furthermore, the type of region groups (countryside region, small city, or medium city) also plays a crucial role in determining the magnitude of the change in precipitation trends for each region. This further lends credibility to the notion that urbanization contributes to changes in precipitation trends.
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Crecimiento Demográfico , Urbanización , Humanos , Población Urbana , Demografía , Vietnam , Geografía , Países en DesarrolloRESUMEN
Huperzine A (HupA) is an important drug for treating Alzheimer's disease (AD) and is primarily extracted from the Huperzia serrata (Lycopodiaceae). Failures in the chemical synthesis of Hup and in vitro culture have put H. serrata in danger of extinction, and there is a need for an extensive investigation of Hup from alternative perspectives. The aim of this study is to identify endophytic fungi that produce high Hup or simultaneously produce many types of Hup and have high genetic stability derived from other Lycopodiaceae species as a source of materials for natural Hup production. In this work, Hup-producing endophytic fungi were isolated from three species: Lycopodium clavatum, Phlegmariurus squarrosus, and P. phlegmaria. Of these, L. clavatum and P. squarrosus were confirmed as novel sources of Hup-producing fungi. Based on morphological characteristics and nuclear ribosomal DNA ITS sequences, four endophytic fungi Colletotrichum siamense THG1-17, Epicoccum sorghinum THG01-18, Phoma sp. TKH3-2, and Phyllosticta sp. THG2-27 were firstly isolated from these Lycopodiaceae plants, which were capable of simultaneously producing both HupA and HupB, as evidenced by high-performance liquid chromatography analysis. The four strains showed stability in Hup yield over 50 generations of culture with an in vitro storage period of 3 months. These isolated fungi will provide a new source of materials for further research to develop drugs containing HupA as well as HupB for AD treatment in the future.
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Introduction: Ovarian metastatic squamous carcinoma of the cervix is rare, accounting for about 0.4%. This study reports a single case of metastatic recurrent cervical cancer in the ovary. Case presentation: A 46-year-old patient with a history of cervical cancer T1b2N0M0 underwent a radical hysterectomy, bilateral pelvic lymph node dissection, and ovarian preservation. One year later, the patient was admitted to the hospital because of abdominal pain in the left iliac fossa; the abdominal computed tomography image showed a left ovarian tumour. The patient underwent laparoscopic left oophorectomy. Postoperative histopathology confirmed ovarian squamous cell carcinoma. From this case, we would like to review the literature on epidemiology, diagnosis, treatment, and prognosis. Clinical discussion: Ovarian preservation during surgery in patients with cervical cancer offers many benefits, but careful patient selection is required. However, it should be selected carefully and closely monitored. Conclusions: Clinicians should be aware of this situation of ovarian metastasis in patients with early cervical cancer undergoing ovarian-conserving surgery.
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Surveillance is the backbone of any response to an infectious disease outbreak, and comprehensive evaluation of surveillance systems is crucial. However, structured evaluations of surveillance systems during the COVID-19 pandemic are scarce. We conducted an after action review (AAR) of the performance of the COVID-19 surveillance system in Quang Ninh Province, Vietnam, during 2020 using the COVID-19-specific AAR methodology developed by the World Health Organization in combination with guidance from the US Centers for Disease Control and Prevention (CDC). We conducted a stakeholder survey, document reviews, and key informant interviews with staff from Quang Ninh CDC's COVID-19 surveillance system. The COVID-19 surveillance system was based on the pre-existing surveillance system in the province. The system's strengths were early preparation for emergency response, strong governance and central coordination, and multidisciplinary collaboration. Stakeholders agreed that the system proved useful and adaptive to the fast-evolving COVID-19 situation but was weakened by overly complex systems, redundant administrative processes, unclear communication channels, and lack of resources. Overall, the surveillance systems in Quang Ninh province proved effective in containing COVID-19 and adaptive in a fast-changing epidemiological context. Several recommendations were made based on identified areas of concern that are of relevance for COVID-19 surveillance systems in Vietnam and similar settings.
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COVID-19 , Pandemias , Estados Unidos , Humanos , Vietnam/epidemiología , Pandemias/prevención & control , COVID-19/epidemiología , Brotes de EnfermedadesRESUMEN
Major advances in the treatment of multiple myeloma (MM) have been achieved by effective new agents such as proteasome inhibitors, immunomodulatory drugs, or monoclonal antibodies. Despite significant progress, MM remains still incurable and, recently, cellular immunotherapy has emerged as a promising treatment for relapsed/refractory MM. The emergence of chimeric antigen receptor (CAR) technology has transformed immunotherapy by enhancing the antitumor functions of T cells and natural killer (NK) cells, leading to effective control of hematologic malignancies. Recent advancements in gene delivery to NK cells have paved the way for the clinical application of CAR-NK cell therapy. CAR-NK cell therapy strategies have demonstrated safety, tolerability, and substantial efficacy in treating B cell malignancies in various clinical settings. However, their effectiveness in eliminating MM remains to be established. This review explores multiple approaches to enhance NK cell cytotoxicity, persistence, expansion, and manufacturing processes, and highlights the challenges and opportunities associated with CAR-NK cell therapy against MM. By shedding light on these aspects, this review aims to provide valuable insights into the potential of CAR-NK cell therapy as a promising approach for improving the treatment outcomes of MM patients.
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Persea americana Mill. (Lauraceae), commonly known as avocado, is a well-known food because of its nutrition and health benefits. The seeds of avocado are major byproducts, and thus their phytochemicals and bioactivities have been of interest for study. The chemical components of avocado seeds were investigated by using UPLC-qTOF-MS/MS-based molecular networking, resulting in the isolation of seven new oxindole alkaloids (1-7) and two new benzoxazinone alkaloids (8 and 9). The chemical structures of the isolated compounds were identified by the analysis of NMR data in combination with computational approaches, including NMR and ECD calculations. Bioactivities of the isolated compounds toward silent information regulation 2 homologue-1 (SIRT1) in HEK293 cells were assessed. The results showed that compound 1 had the most potent effect on SIRT1 activation with an elevated NAD+/NADH ratio with potential for further investigation as an anti-aging agent.
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Alcaloides , Persea , Humanos , Persea/química , Oxindoles/farmacología , Benzoxazinas/análisis , Espectrometría de Masas en Tándem , Sirtuina 1 , Células HEK293 , Semillas/química , Alcaloides/farmacología , Alcaloides/análisis , Extractos Vegetales/químicaRESUMEN
Vietnamese ginseng (Panax vietnamensis Ha and Grushv., Araliaceae) is indigenous in the central highlands of Vietnam and the southernmost distribution in the Panax genus. Like other ginseng, Vietnamese ginseng is well known has been used as a tonic and for management of certain diseases in the traditional medicine. Nevertheless, it is noteworthy that in respect to the long history in use and systematic studied on Korean ginseng (P. ginseng), American ginseng (P. quinquefolius), Japanese ginseng (P. japonicus), and Chinese ginseng (P. notoginseng), the up-to-date published database on Vietnamese ginseng is relatively much less extensive. In our ongoing research on the promising Vietnamese medicinal plants, the present phytochemical investigation of the ethanol extract of the leaves of Panax vietnamensis led to the isolation of three compounds (1-3), including a new indole alkaloid N-glycoside (1) and two known compounds. Their structures were elucidated based on extensive physiochemical and chemical methods, especially the interpretation of NMR and MS spectra. The absolute configuration of 1 was determined based on the comparison of its experimental and theoretical ECD spectra along with NMR calculation. Compound 1 is naturally isolated N-glycoside, which is rarely found in natural products. The isolated compounds showed weak or no inhibitory activity against acetylcholinesterase enzyme (AChE).
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Glucósidos , Panax , Acetilcolinesterasa , Glucósidos/química , Panax/química , Hojas de la Planta/química , VietnamRESUMEN
While screening senotherapeutics from natural products, seven undescribed chemicals, two syringylglycerol derivatives, two cyclopeptides, one tigliane analogue, and two chromone derivatives, as well as six known compounds were isolated from the stems of Limacia scandens. The structures of compounds were elucidated through spectroscopic data analysis, including 1D and 2D NMR, HRESIMS, and CD data. All compounds were tested in replicative senescent human dermal fibroblasts (HDFs) to determine their potential as senotherapeutic agents to specifically target senescent cells. One tigliane and two chromones derivatives showed senolytic activity, indicating that senescent cells were selectively removed. Especially, 2-{2-[(3'-O-ß-d-glucopyranosyl)phenyl]ethyl}chromone is expected to be a potential senotherapeutics by inducing HDF death, inhibiting the activity of senescence-associated ß-galactosidase (SA-ß-gal) and expressing senescence-associated secretory phenotype (SASP) factors.
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Senescencia Celular , Senoterapéuticos , Humanos , Células Cultivadas , Fibroblastos , Cromonas/farmacologíaRESUMEN
Surveillance is the backbone of any response to an infectious disease outbreak, and comprehensive evaluation of surveillance systems is crucial. However, structured evaluations of surveillance systems during the COVID-19 pandemic are scarce. We conducted a after action review (AAR) of the performance of the COVID-19 surveillance system in Quang Ninh Province, Vietnam, during 2020 using the COVID-19-specific AAR methodology developed by the World Health Organization in combination with guidance from the US Centers for Disease Control and Prevention (CDC). We conducted a stakeholder survey, document reviews, and key informant interviews with staff from Quang Ninh CDC's COVID-19 surveillance system. The COVID-19 surveillance system was based on the pre-existing surveillance system in the province. The system's strengths were early preparation for emergency response, strong governance and central coordination, and multidisciplinary collaboration. Stakeholders agreed that the system proved useful and adaptive to the fast-evolving COVID-19 situation but was weakened by overly complex systems, redundant administrative processes, unclear communication channels, and lack of resources. Overall, the surveillance systems in Quang Ninh province proved effective in containing COVID-19 and adaptive in a fast-changing epidemiological context. Several recommendations were made based on identified areas of concern that are of relevance for COVID-19 surveillance systems in Vietnam and similar settings.
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COVID-19 , Pandemias , Estados Unidos , Humanos , Vietnam/epidemiología , COVID-19/epidemiología , Brotes de EnfermedadesRESUMEN
PM2.5 pollution is a serious problem in Vietnam and around the world, having bad impacts on human health, animals and environment. Regular monitoring at a large scale is important to assess the status of air pollution, develop solutions and evaluate the effectiveness of policy implementation. However, air quality monitoring stations in Vietnam are limited. In this article, we propose an approach to estimate daily PM2.5 concentration from 2012 to 2020 over the Vietnamese territory, which is strongly affected by cloudy conditions, using a modern statistical model named Mixed Effect Model (MEM) on a dataset consisting of ground PM2.5 measurements, integrated satellite Aerosol Optical Depth (AOD), meteorological and land use maps. The result of this approach is the first long-term, full coverage and high quality PM2.5 dataset of Vietnam. The daily mean PM2.5 maps have high validation results in comparison with ground PM2.5 measurement (Pearson r of 0.87, R2 of 0.75, RMSE of 11.76 µg/m3, and MRE of 36.57 % on a total of 13,886 data samples). The aggregated monthly and annual average maps from 2012 to 2020 in Vietnam have outstanding quality when compared with another global PM2.5 product. The PM2.5 concentration maps has shown spatial distribution and seasonal variations of PM2.5 concentration in Vietnam in a long period from 2012 to 2020 and has been used in other studies and applications in the environment and public health at the national scale, which has not been possible before because of the lack of monitoring stations and an appropriate PM2.5 modeling approach.
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Contaminantes Atmosféricos , Contaminación del Aire , Humanos , Material Particulado/análisis , Contaminantes Atmosféricos/análisis , Monitoreo del Ambiente/métodos , Vietnam , Contaminación del Aire/análisis , Aerosoles/análisisRESUMEN
OBJECTIVES: To compare the safety and efficacy of combined laser iridoplasty followed by surgical iridectomy (LI-SI) versus trabeculectomy in the management of medically unresponsive acute primary angle closure (APAC) with minimal cataract. PATIENTS AND METHODS: This was a randomized controlled trial conducted among patients with medically unresponsive APAC without significant cataract. Study participants were randomized into: LI-SI or unaugmented trabeculectomy. Primary outcome of the study was the rate of post-operative surgical complications in the first 3 months after surgery. Secondary outcome assessed at 1 year was whether treatment was completely successful (IOP < 21 mmHg without IOP lowering drops), or partially successful (IOP < 21 mmHg with IOP lowering drops). Failure was defined as IOP ≥ 21 mmHg with IOP lowering drops. RESULTS: The study included 67 eyes of 67 patients (59 females/8 males = 7.4/1) who were randomized into 2 groups: LI-SI (Group 1, 37 eyes), and trabeculectomy (Group 2, 30 eyes). There was no statistical difference between the two groups at baseline. Overall, there were more post-operative complications in Group 1 versus Group 2 (45.9% versus 33.3% - p = 0.23), although all responded well to medical treatment and resolved without sequelae. Complete success was found in 97.1% (34/35 eyes) in Group 1 and 92.6% in group 2 (p = 0.19, Fisher's exact test). CONCLUSIONS: There was a higher rate of post-operative complications after LI-SI compared to trabeculectomy performed for medically unresponsive APAC with minimal cataract. Both procedures had similar surgical outcomes at 1 year.
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Catarata , Glaucoma de Ángulo Cerrado , Trabeculectomía , Masculino , Femenino , Humanos , Trabeculectomía/métodos , Iridectomía , Presión Intraocular , Catarata/complicaciones , Iris/cirugía , Rayos Láser , Resultado del Tratamiento , Glaucoma de Ángulo Cerrado/cirugía , Glaucoma de Ángulo Cerrado/complicacionesRESUMEN
Chemical investigation of the plant Gymnema latifolium led to the isolation of seven undescribed 23-glycosyl oleanane triterpenoids, gymlatinosides GLF1-GLF7, and two known compounds, gymnemosides D and E. The structures of the isolated compounds were elucidated using diverse spectroscopic methods. The extract of G. latifolium and all isolated compounds significantly enhanced 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxyglucose (2-NBDG) uptake into 3T3-L1 adipocytes at 20 µM. Among them, gymlatinosides GLF2 and gymlatinosides GLF4 showed particularly potent stimulatory effects on glucose uptake in a dose-dependent manner. Further investigation revealed that gymlatinosides GLF2 at 20 µM upregulated the expression of phosphorylated AMPK (p-AMPK). The results suggested that gymlatinosides GLF2 may enhance glucose uptake via regulating the AMPK signaling pathway.
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Gymnema , Triterpenos , Triterpenos/farmacología , Glucosa , InsulinaRESUMEN
Ten phenolic constituents, including three new macrocyclic glycosides (1-3), a new phenolic glycoside (5), a new biphenyl glycoside (6), and five known compounds (4, 7-10), were isolated from a 70% MeOH extract of the leaves of Heliciopsis terminalis by liquid chromatography-tandem mass spectrometry (LC-MS/MS)-guided molecular networking. The chemical structures of new compounds 1-3, 5 and 6 were established based on comprehensive spectroscopic data analysis, including 1D and 2D NMR and HRESIMS techniques. All isolated compounds (1-10) were evaluated for their stimulation of glucose uptake in differentiated 3T3-L1 adipocytes using 2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]-d-glucose (2-NBDG) as a fluorescent glucose analog. Compounds 3, 6 and 8 showed stimulatory effects on the uptake of 2-NBDG in 3T3-L1 adipocyte cells. Among them, compounds 3 and 6 activated the AMPK signaling pathway in differentiated C2C12 myoblasts.
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Limacia scandens is traditionally used to treat depression and affective disorders in Malaysia. The chemical compositions have been reported to include bisbenzylisoquinoline and aporphine-type alkaloids in the genus Limacia Lour., but studies on the components of L. scandens have rarely been reported. Therefore, this study was conducted to determine new benzylisoquinoline alkaloid derivatives with autophagy regulation activity from this plant. Bioactivity-guided isolation was applied to various column chromatography methods using RP-18, Sephadex LH-20 open column chromatography, and preparative HPLC. The chemical structures of the isolated compounds were elucidated through spectroscopic data analysis, including NMR, HR-ESI-MS, and ECD data. In addition, isolated compounds were tested for autophagy-regulating activity in HEK293 cells expressing GFP-L3. Three new dimeric benzylisoquinoline alkaloids (1-3), one new 4-hydroxybenzoic acid-conjugated benzylisoquinoline alkaloid (4), and six known compounds (5-10) were isolated from the stems of L. scandens. All compounds (1-10) were screened for autophagy regulation in HEK293 cells stably expressing the GFP-LC3 plasmid. Among the isolated compounds, 1, 2, and 4 showed autophagic regulation activity that blocked the process of combining autophagosomes and lysosomes. They also inhibit the protein degradation process from the autolysosome as inhibitors of autophagy. Novel benzylisoquinoline alkaloids from L. scandens showed potent potency for the inhibition of autophagic flux. This study provides potential candidates for developing natural autophagy inhibitors for disease prevention and treatment.