Small-molecule GSDMD agonism in tumors stimulates antitumor immunity without toxicity.

Gasdermin-mediated inflammatory cell death (pyroptosis) can activate protective immunity in immunologically cold tumors. Here, we performed a high-throughput screen for compounds that could activate gasdermin D (GSDMD), which is expressed widely in tumors. We identified 6,7-dichloro-2-methylsulfonyl-3-N-tert-butylaminoquinoxaline (DMB) as a direct and selective GSDMD agonist that activates GSDMD pore formation and pyroptosis without cleaving GSDMD. In mouse tumor models, pulsed and low-level pyroptosis induced by DMB suppresses tumor growth without harming GSDMD-expressing immune cells. Protection is immune-mediated and abrogated in mice lacking lymphocytes. Vaccination with DMB-treated cancer cells protects mice from secondary tumor challenge, indicating that immunogenic cell death is induced. DMB treatment synergizes with anti-PD-1. DMB treatment does not alter circulating proinflammatory cytokine or leukocyte numbers or cause weight loss. Thus, our studies reveal a strategy that relies on a low level of tumor cell pyroptosis to induce antitumor immunity and raise the possibility of exploiting pyroptosis without causing overt toxicity.

Structural transitions enable interleukin-18 maturation and signaling.

Several interleukin-1 (IL-1) family members, including IL-1ß and IL-18, require processing by inflammasome-associated caspases to unleash their activities. Here, we unveil, by cryoelectron microscopy (cryo-EM), two major conformations of the complex between caspase-1 and pro-IL-18. One conformation is similar to the complex of caspase-4 and pro-IL-18, with interactions at both the active site and an exosite (closed conformation), and the other only contains interactions at the active site (open conformation). Thus, pro-IL-18 recruitment and processing by caspase-1 is less dependent on the exosite than the active site, unlike caspase-4. Structure determination by nuclear magnetic resonance uncovers a compact fold of apo pro-IL-18, which is similar to caspase-1-bound pro-IL-18 but distinct from cleaved IL-18. Binding sites for IL-18 receptor and IL-18 binding protein are only formed upon conformational changes after pro-IL-18 cleavage. These studies show how pro-IL-18 is selected as a caspase-1 substrate, and why cleavage is necessary for its inflammatory activity.

ROS-dependent S-palmitoylation activates cleaved and intact gasdermin D.

Gasdermin D (GSDMD) is the common effector for cytokine secretion and pyroptosis downstream of inflammasome activation and was previously shown to form large transmembrane pores after cleavage by inflammatory caspases to generate the GSDMD N-terminal domain (GSDMD-NT)1-10. Here we report that GSDMD Cys191 is S-palmitoylated and that palmitoylation is required for pore formation. S-palmitoylation, which does not affect GSDMD cleavage, is augmented by mitochondria-generated reactive oxygen species (ROS). Cleavage-deficient GSDMD (D275A) is also palmitoylated after inflammasome stimulation or treatment with ROS activators and causes pyroptosis, although less efficiently than palmitoylated GSDMD-NT. Palmitoylated, but not unpalmitoylated, full-length GSDMD induces liposome leakage and forms a pore similar in structure to GSDMD-NT pores shown by cryogenic electron microscopy. ZDHHC5 and ZDHHC9 are the major palmitoyltransferases that mediate GSDMD palmitoylation, and their expression is upregulated by inflammasome activation and ROS. The other human gasdermins are also palmitoylated at their N termini. These data challenge the concept that cleavage is the only trigger for GSDMD activation. They suggest that reversible palmitoylation is a checkpoint for pore formation by both GSDMD-NT and intact GSDMD that functions as a general switch for the activation of this pore-forming family.

Chopped! Newfound GSDMD cleavage facilitates tolerance to food allergens.

In a recent article, He et al. report that, in response to dietary protein antigens, mouse intestinal epithelial cells (IECs) accumulate a newfound 13-kDa N terminus of gasdermin D (GSDMD-N13), cleaved by caspase-3/7. Unlike the pyroptotic 30-kDa fragment, GSDMD-N13 translocates to the nucleus, inducing CIITA and major histocompatibility complex class II (MHCII) expression to promote type 1 regulatory T (T1r) cell development, thus revealing its role in balancing immunity and food tolerance.

Bimodal Droplet-Based Electricity Generation Through Semi Cassini Oval Dynamic Morphology Control.

Droplet-based electricity generator (DEG) is the promising energy harvesting technology applicable in versatile scenarios. Despite numerous optimizations in DEG's materials and structures, few has paid attention to the droplet dynamics and morphology control. Here the droplet's spread-retraction dynamics and the resultant semi Cassini oval (SCO) morphology are reported, characterized by convex at both ends and concave in the middle. The lifted top electrode (LTE) is designed to respond to the dynamic SCO morphology in two steps: 1) LTE first contacts the leading edge of the spreading droplet, generating a negative voltage peak; 2) LTE second contacts the trailing edge of the retracting droplet, generating a positive voltage peak. In this way, bimodal electrical output is obtained, which exhibits 25% increase in peak-to-peak voltage and 33% increase in average power compared to the traditional DEG with only one voltage peak. These results prove that incorporating the droplet dynamics and morphology control into DEG design uplifts the energy harvesting limit from individual droplet. The proposed LTE-DEG inspires alternative route for DEG power enhancement by maximizing energy utilization of individual droplet from the perspective of droplet dynamic morphology design.

Expression of a thermostable glucose-stimulated ß-glucosidase from a hot-spring metagenome and its promising application to produce gardenia blue.

This study reports a thermostable glucose-stimulated ß-glucosidase, BglY442, from hot-spring metagenomic data that was cloned and expressed in Escherichia coli BL21 (DE3). The molecular mass of recombinant BglY442 was 69.9 kDa and was used in the production of gardenia blue. The recombinant BglY442 showed its maximum activity at pH 6.0 and 75 °C, maintained 50 % activity at 70 °C for 36 h, presented over 90 % activity in a broad pH range and a wide range of pH stability. Moreover, BglY442 exhibited excellent tolerance toward methanol and ethanol. The specific activity of BglY442 was 235 U/mg at pH 6.0 and 75 °C with 10 mM pNPG as substrate. BglY442 activity increased by over fourfold with 2 M glucose or xylose. Specifically, the enzyme kinetics of BglY442 seem to be non-Michaelis-Menten kinetics or atypical kinetics because the Michaelis-Menten saturation kinetics were not observed with pNPG, oNPG or geniposide as substrates. Under optimum conditions, geniposide was dehydrated by BglY442 and reacted with nine amino acids respectively by the one-pot method. Only the Arg or Met derived pigments showed bright blue, and these two pigments had similar ultraviolet absorption spectra. The OD590 nm of GB was detected to be 1.06 after 24 h with the addition of Arg and 1.61 after 36 h with the addition of Met. The intermediate was elucidated and identified as ginipin. Molecular docking analysis indicated that the enzyme had a similar catalytic mechanism to the reported GH1 Bgls. BglY442 exhibited potential for gardenia blue production by the one-pot method. With outstanding thermostability and glucose tolerance, BglY442 should be considered a potential ß-glucosidase in biotechnology applications.

Simplicispira sedimenti sp. nov., isolated from a sediment of drainage ditch in winery.

A Gram-stain-negative, motile (by single polar flagellum) and rod-shaped bacterium, designated W1-6T, was isolated from a sediment of drainage ditch in winery in Guiyang, south-western China. Strain W1-6T showed the highest 16S rRNA gene sequence similarities with the type strain of Acidovorax wautersii (98.1%) and Simplicispira lacusdiani (97.9%). Phylogenetic analysis based on 16S rRNA gene sequences showed that strain W1-6T was placed adjacent to the members of the genus Simplicispira and formed a separat subclade. Cells showed oxidase and catalase negative reactions. The only respiratory quinone detected was ubiquinone-8 (Q-8). Summed feature 3 (C16:1 ω7c and/or C16:1 ω6c), C16:0 and summed feature 8 (C18:1 ω7c and/or C18:1 ω6c) were predominant cellular fatty acids (> 10%) of strain W1-6T. Diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and five unidentified phospholipids were found in the polar lipid extraction. The genomic DNA G + C content was 65.6%. Strain W1-6T shared the highest digital DNA-DNA hybridization [dDDH, (27.6%)] and average nucleotide identity [ANI (84.3%)] values with the type strain of S. lacusdiani. The dDDH and ANI values were below the cutoff level (dDDH 70%; ANI 95-96%) for species delineation. The polyphasic characteristics indicated that the strain W1-6T represents a novel species of the genus Simplicispira, for which the name Simplicispira sedimenti sp. nov. is proposed. The type strain is W1-6T (= CGMCC 1.16274T = NBRC 115624T).

Characterization of the transcriptional responses of Armillaria gallica 012m to GA3.

Gastrodia elata needs to establish a symbiotic relationship with Armillaria strains to obtain nutrients and energy. However, the signaling cross talk between G. elata and Armillaria strains is still unclear. During our experiment, we found that the vegetative mycelium of Armillaria gallica 012m grew significantly better in the media containing gibberellic acid (GA3) than the blank control group (BK). To explore the response mechanism, we performed an RNA-sequencing experiment to profile the transcriptome changes of A. gallica 012m cultured in the medium with exogenous GA3. The transcriptome-guided differential expression genes (DEGs) analysis of GA3 and BK showed that a total of 1309 genes were differentially expressed, including 361 upregulated genes and 948 downregulated genes. Some of those DEGs correlated with the biological process, including positive regulation of chromosome segregation, mitotic metaphase/anaphase transition, attachment of mitotic spindle microtubules to kinetochore, mitotic cytokinesis, and nuclear division. These analyses explained that GA3 actively promoted the growth of A. gallica to some extent. Further analysis of protein domain features showed that the deduced polypeptide contained 41 candidate genes of GA receptor, and 27 of them were expressed in our samples. We speculate that GA receptors exist in A. gallica 012m. Comparative studies of proteins showed that the postulated GA receptor domains of A. gallica 012m have a higher homologous correlation with fungi than others based on cluster analysis.

Laparoscopic versus open surgery for hepatic caudate lobectomy: a retrospective study.

BACKGROUND: This study was designed to investigate the feasibility and safety of laparoscopic hepatic caudate lobectomy (LHCL) for treating liver tumor by comparing with the open hepatic caudate lobectomy (OHCL). METHODS: In the LHCL group, we included 24 patients with liver tumor received LHCL in Qilu Hospital of the Shandong University from January 2014 to January 2019. Meanwhile, 24 matched liver tumor patients underwent OHCL in our hospital served as control. Then we compared the patient characteristics, intraoperative parameters, and postoperative outcomes between LHCL group and OHCL group. RESULTS: There were no significant differences in gender, age, degree of cirrhosis, tumor size, preoperative liver function, Child-Pugh grading, proportion of liver cirrhosis, and tumor size between LHCL group and OHCL group (P > 0.05). No death was reported in both groups. The length of incision in LHCL group was significantly lower than that in OHCL group (4.22 ± 1.14 cm vs. 22.46 ± 4.40 cm, P < 0.001). The intraoperative blood loss in LHCL group was significantly lower than that of OHCL group (116.82 ± 71.61 ml vs. 371.74 ± 579.35 ml, P = 0.047). The total operation time, Pringle maneuver occlusion time, and blocking rate in LHCL group showed no statistical difference compared with those of the OHCL group (P > 0.05). The VAS scores at postoperative 24 and 48 h showed no statistical differences between LHCL group and OHCL group (P > 0.05). Compared with the OHCL group, significant decrease was noticed in the proportion of patients with severe pain 48 h after surgery (0 vs. 4.25 ± 0.46, P < 0.001) and dezocine consumption (90.45 ± 45.77 mg vs. 131.6 ± 81.30 mg, P = 0.0448) in the LHCL group. CONCLUSION: LHCL is effective and feasible for treating liver tumor, which is featured by reducing intraoperative blood loss and serious pain.

Transcriptome analysis of Armillaria gallica 012 m in response to auxin.

Gastrodia elata is an achlorophyllous and fully mycoheterotrophic orchid which obtains carbon and other nutrients from Armillaria species in its life cycle. Many researchers suggested that plant hormones, as signing molecules, play a central role in the plant-fungi interaction. In the process of Armillaria gallica 012 m cultivation, both exogenous indole-3-acetic acid (IAA) and indole-3-butyric acid (IBA) distinctly stimulated the growth of mycelia in solid media. The differential expression genes (DEGs) of A. gallica 012 m with IAA versus blank control (BK) and IBA versus BK were investigated. The results showed that more than 80% of DEGs of the IAA group were coincident with the DEGs of the IBA group, and more than half of upregulated DEGs and most of the downregulated DEGs of the IAA group coincided with those DEGs of the IBA group. Above research implied that A. gallica 012 m could perceive IAA and IBA, and possess similar responses and signaling pathways to IAA and IBA. The overlapping differential genes of the IAA group and IBA group were analyzed by GO term, and the results showed that several DEGs identified were related to biological processes including positive regulation of the biological process and biological process. The downregulated NmrA-like and FKBP_C genes might be benefit to the growth of mycelia. Those results can explain that exiguous IAA and IBA improved the growth of A. gallica to some extent. We speculate that IAA and IBA are signaling molecules, and regulate the expression of growth-related genes of A. gallica 012 m by the same signaling pathway.

Cyclic hexadepsipeptides from the fermentation of Fusarium sp. DCJ-A and their cytotoxic activities.

Beauvercin H (1), a new cyclic hexadepsipeptide, and two known ones (2 and 3) were isolated from the EtOH extract of the solid culture of Fusarium sp. Their structures were elucidated by spectroscopic analysis, including extensive 1D and 2D NMR techniques, as well as comparison with literature values. Additionally, compounds 1-3 were tested for their cytotoxic activities. The results showed that all isolated compounds exhibited cytotoxic activities against five human cancer cell lines with IC50 values ranging from 1.379 to 13.12 µM.

Fast hyperspectral single-pixel imaging via frequency-division multiplexed illumination.

Hyperspectral imaging that detects 3D spectra-spatial information has been used in a wide range of applications. Among reported techniques, multiplexed spectral imaging with a single-pixel detector provides as a photon-efficient and low-cost implementation; however, the previous spectral modulation schemes are mostly complicated and sacrifice the imaging speed. Here, we propose a fast and compact hyperspectral single-pixel imaging technique based on programmable chromatic illumination. A multi-wavelength LED array modulated by independent carriers achieves stable and accurate spectral modulation up to MHz in a frequency-division multiplexed manner, hence allowing the full use of the spatial light modulation speed. Additionally, we propose a multi-channel deep convolutional autoencoder network to reconstruct hyperspectral data from highly-compressed 1D measurement. Experimental reconstructions of 12 spectral channels and 64 × 64 pixels are demonstrated for dynamic imaging at 12 fps image rate. The proposed imaging scheme is highly extensible to a wide spectrum range, and holds potential for portable spectral imagers in low-light or scattering applications.

Lipoic acid rejuvenates aged intestinal stem cells by preventing age-associated endosome reduction.

The age-associated decline of adult stem cell function is closely related to the decline in tissue function and age-related diseases. However, the underlying mechanisms that ultimately lead to the observed functional decline of stem cells still remain largely unexplored. This study investigated Drosophila midguts and found a continuous downregulation of lipoic acid synthase, which encodes the key enzyme for the endogenous synthesis of alpha-lipoic acid (ALA), upon aging. Importantly, orally administration of ALA significantly reversed the age-associated hyperproliferation of intestinal stem cells (ISCs) and the observed decline of intestinal function, thus extending the lifespan of Drosophila. This study reports that ALA reverses age-associated ISC dysfunction by promoting the activation of the endocytosis-autophagy network, which decreases in aged ISCs. Moreover, this study suggests that ALA may be used as a safe and effective anti-aging compound for the treatment of ISC-dysfunction-related diseases and for the promotion of healthy aging in humans.

Laparoscopic versus open surgery for hilar cholangiocarcinoma: a retrospective cohort study on short-term and long-term outcomes.

BACKGROUND: Laparoscopic surgery (LS) for hilar cholangiocarcinoma (HCCa) remains under development, and its feasibility and safety remain controversial. This study therefore evaluated the outcomes of this technique and compared them to those of open surgery (OS). METHODS: In total, 149 patients underwent surgical resection for HCCa at our center between February 2017 and September 2020. After screening and propensity score matching, 47 OS group patients and 20 LS group patients remained, and their baseline characteristics, pathologic findings, surgical outcomes, and long-term outcomes were compared. RESULT: The baseline characteristics and pathologic findings were comparable between the two groups. The mean incision length was longer in the OS group than in the LS group (21.0 cm vs. 13.2 cm, P < 0.001). No significant differences were observed in the other surgical outcomes between the two groups. Regarding long-term outcomes, the overall survival rate and disease-free survival rate of the OS group were significantly higher than those of the LS group (P = 0.0057, P = 0.043). However, the two groups had significantly different follow-up times (19.2 months vs. 14.7 months, P = 0.041). CONCLUSION: LS for HCCa is technically achievable, and our study revealed that it is equivalent to OS in terms of short-term outcomes but was poorer in terms of long-term outcomes.

Laparoscopic versus open hepatectomy for intrahepatic cholangiocarcinoma in patients aged 60 and older: a retrospective cohort study.

Objective laparoscopic surgical excision is the recommended treatment for liver cancers, yet its benefits in patients aged 60 and older remain poorly understood. Thus, this study evaluated the feasibility, safety, and clinical outcomes of laparoscopic hepatectomy for patients aged 60 and older with intrahepatic cholangiocarcinoma (ICC).MethodsAfter screening, 107 patients who underwent hepatectomy for ICC were enrolled and grouped into either laparoscopic (LH) or open hepatectomy (OH) groups. Baseline characteristics, pathological findings, and long-term outcomes were compared between the two groups. Independent prognostic factors for overall survival (OS) and disease-free survival (DFS) were identified using univariate and multivariate analyses.ResultsAmong baseline characteristics and pathological findings, only pre-operative albumin was higher in the LH group. The LH group had more favorable short-term outcomes such as incision length, level of postoperative total bilirubin, and length of postoperative stays than the OH group. The postoperative complication, lymph node dissection and R0 resection rate, and long-term outcomes including OS and DFS were not significantly different between the two groups. Cancer Antigen-19-9(CA-19-9) and pathological differentiation were independent prognostic factors for OS, whereas CA-19-9 and neutrophil count were independent prognostic factors for DFS.ConclusionLH is safe, reliable, and feasible for treatment of ICC patients aged 60 and older as it had better short-term clinical outcomes than OH and achieved long-term prognoses that were comparable to those of OH.

Differential Proteomic and Genomic Comparison of Resistance Mechanism of Pseudomonas aeruginosa to Cefoperazone Sodium/Sulbactam Sodium.

The aim of this study was to determine the resistance mechanism of Pseudomonas aeruginosa to cefoperazone sodium/sulbactam sodium. We retrospectively analyzed the drug resistance of P.a isolated at the First Affiliated Hospital of Guangxi Medical University. Drug-resistant P.a strains were constructed, then wild-type (WT) and drug-resistant (DR) strains were compared using protein and gene microarrays to determine differences between DR and WT strains. The resistance rates of P. aeruginosa during 2013, 2014 and 2015 were 21.2%, 21.4%, and 24.6% respectively. Among 242 protein peaks of WT and DR bacteriophage proteins, 41 were differentially expressed between the two groups. The expression of 26 and 15 proteins were respectively upregulated and downregulated in the DR compared with the WT group. Gene microarray results revealed 679 mutant loci in the DR group, of which 42 with the top 50 Q values were found in the NCBI database. The rate of P.a resistance to cefoperazone sodium/sulbactam sodium remained high between 2013 and 2015. The numbers of different proteins and genetic variations in the DR strains suggested that the resistance mechanism of P.a to cefoperazone sodium/sulbactam sodium involves multiple genes and proteins that might be key to controlling P.a resistance to cefoperazone sodium/sulbactam sodium.

Two new sesquiterpene aryl esters from Armillaria gallica 012m.

Two new sesquiterpene aryl esters, armimelleolides A and B (1 and 2), and four known ones, were isolated from the EtOAc extract of Armillaria gallica 012 m by column chromatography on silica gel, reversed-phase C18 silica gel and semi-preparative HPLC. Their structures were elucidated on the basis of spectroscopic methods, including extensive 1 D NMR, 2 D NMR and MS. All these compounds showed potential antitumor activities against at least one of the human cancer cell lines (A549, HCT-116, M231 and W256), with IC50 ranging from 2.57 to 19.94 µM.

Azospirillum tabaci sp. nov., a bacterium isolated from rhizosphere soil of Nicotiana tabacum L.

Strain W712T was isolated from rhizosphere soil of Nicotiana tabacum L. collected from Kunming, south-west China. Cells were Gram-staining negative, aerobic, motile and rod shaped. The isolate grew at 20-45 °C (optimum 30 °C), pH 6.0-8.0 (optimum pH 7.0) and in the presence of up to 3.0% (w/v) NaCl (optimum 1%, w/v). Ubiquinone-10 was the only respiratory quinone type. Polar lipids contained diphosphatidylglycerol, phosphatidylmehtylethanolamine, phosphatidylglycerol, phosphatidylcholine and an unidentified aminolipid. The major fatty acids were detected as summed feature 8 (C18:1 ω7c or C18:1 ω6c), summed feature 3 (C16:1 ω7c or C16:1 ω6c) and C18:1 2OH. The genomic DNA G + C content was 68.7%. The ANI values were 94.3%, 93.3% and 93.6% between Azospirillum baldaniorum Sp245T, Azospirillum brasilense ATCC 49958T, Azospirillum formosense CC-Nfb-7T and strain W712T, respectively, which were lower than the prokaryotic species delineation threshold of 95.0-96.0%. The digital DNA-DNA hybridization values between A. baldaniorum Sp245T, A. brasilense ATCC 49958T, A. formosense CC-Nfb-7T and strain W712T indicated that the candidate represents a novel genomic species. According to the phenotypic and genotypic characteristics, we propose that strain W712T warrants the assignment to a novel species, for which the name Azospirillum tabaci sp. nov. (type strain W712T = CGMCC 1.18567T = KCTC 82186T) is proposed.

A new modified Gant-Miwa-Thiersch combined with submucosal and perirectal sclerosant injection procedure for full-thickness rectal prolapse in elderly women: clinical analysis of 34 cases.

BACKGROUND: Full-thickness rectal prolapse (FTRP) frequently occurs in elderly women, and more than 100 surgical procedures have been proposed to restore FTRP. The Gant-Miwa-Thiersch (GMT) procedure is the most used treatment in China. However, the recurrence rate of FTRP post-GMT, which is as high as 23.8%, is concerning. We described a new modified GMT combined with internal and external rectal sclerosant injection (nmGMTSI) procedure to address this problem. METHODS: The nmGMTSI was performed under spinal anesthesia in 34 frail, elderly female patients with FTRP. The surgical results of FTRP were assessed. Fecal incontinence and constipation were evaluated using the Wexner score, and anal canal rest pressure (ACRP), maximum anal systolic pressure (MASP), anorectal sensation thresholds (AST), and maximum rectal tolerance (MRT) using anorectal manometry preoperatively and postoperatively. The causes of recurrence and complications were analyzed. RESULTS: All patients were cured according to the clinical cure standard. The perioperative Wexner fecal incontinence score (WFIS) was 10.3 ± 3.31, which became 3.7 ± 2.43 (P < 0.0001) postoperatively. The perioperative ACRP was 2.0 ± 0.56 kPa, which became 8.5 ± 2.25 kPa (P < 0.0001) postoperatively. The perioperative MASP was 4.5 ± 1.16 kPa, which became 18.6 ± 2.50 kPa (P < 0.0001) postoperatively. However, no significant difference was observed between the preoperative and postoperative Wexner constipation scores (WCS) (17.3 ± 2.25 vs. 15.4 ± 2.89, P = 0.1047). The perioperative and postoperative AST were 38.1 ± 5.34 mL and 23.5 ± 3.61 mL, respectively (P = 0.0002). The maximum rectal tolerance (MRT) was 157.1 ± 16.73 mL, which became 121.2 ± 12.45 mL postoperatively (P = 0.0009). The patients developed no serious postoperative complications. The total relapse rate after nmGMTSI was 2.9% in the median two years follow-up period. The most common cause of relapse after nmGMTSI was the removal of infected threads used in the Thiersch procedure. CONCLUSION: The benefits of nmGMTSI include low rates of recurrence, complications, and mortality, cost-effectiveness, wide adaptation, minimal invasiveness, and technical simplicity. Hence, it should be considered the first option for the treatment of FTRP in frail elderly women.

[Guiding mechanism of platycodin D in treatment of mouse lung cancer with doxorubicin].

This study is to observe whether platycodin D has the guiding role in treatment of mouse lung cancer with doxorubicin and explore its guiding mechanism. In vitro, platycodin D and doxorubicin(alone or in combination) were added into Lewis lung cancer(LLC) cells to detect the cell proliferation and doxorubicin uptake. Cell morphological changes were analyzed by cell holographic analysis system; cell gap junctional intercellular communication(GJIC) was tested by fluorescent yellow tracer; lyso-tracker red was used to examine lysosomal function; LC-3 B(Light chain 3 beta)and P62(heat shock 90-like protein)staining were used to test auto-phagy and autophagic degradation respectively; and P-glycoprotein(P-gp) expression was examined by Western blot. In vivo, lung solid tumor was formed in mouse LLC cells via intravenous injection. Platycodin D and doxorubicin(alone or in combination) were used to treat tumor-bearing mice for four weeks, and then the tumor size was examined, mouse survival time was recorded, doxorubicin uptake in lung tissues was tested, and lung tissues were stained for observation by HE(hematoxylin-eosin) and immunohistochemistry. The results showed that platycodin D at the experimental concentration had no effect on LLC cell proliferation but decreased LLC cell volume, promoted the cells to uptake doxorubicin and enhanced the inhibitory action of doxorubicin on cell proliferation. Platycodin D could promote GJIC and lysosomal function, increase autophagy and autophagic degradation and suppress P-gp expression. Platycodin D at the experimental dose in this study had no effect on LLC lung solid tumors in mice, increased doxorubicin uptake in lung tissues and enhanced the therapeutic efficacy of doxorubicin on lung solid tumors. Platycodin D could improve the extracellular matrix deposition in lung solid tumors, decreased the lung mucin 5 AC secretion and pulmonary vessel permeability. In summary, platycodin D had the guiding role in treating mouse lung cancer with doxorubicin, and its guiding mechanism may be associated with the promotion of cell communication, lysosomal function, and improvement of extracellular environment.