Expression, purification and refolding of pro-MMP-2 from inclusion bodies of E. coli.

MMP-2 has been reported as the most validated target for cancer progression and deserves further investigation. However, due to the lack of methods for obtaining large amounts of highly purified and bioactive MMP-2, identifying specific substrates and developing specific inhibitors of MMP-2 remains extremely difficult. In this study, the DNA fragment coding for pro-MMP-2 was inserted into plasmid pET28a in an oriented manner, and the resulting recombinant protein was effectively expressed and led to accumulation as inclusion bodies in E. coli. This protein was easy to purify to near homogeneity by the combination of common inclusion bodies purification procedure and cold ethanol fractionation. Then, our results of gelatin zymography and fluorometric assay revealed that pro-MMP-2 at least partially restored its natural structure and enzymatic activity after renaturation. We obtained approximately 11 mg refolded pro-MMP-2 protein from 1 L LB broth, which was higher than other strategies previously reported. In conclusion, a simple and cost-effective procedure for obtaining high amounts of functional MMP-2 was developed, which would contribute to the progress of studies on the gamut of biological action of this important proteinase. Furthermore, our protocol should be appropriate for the expression, purification, and refolding of other bacterial toxic proteins.

Antibody and T-cellular response to COVID-19 booster vaccine in SARS-CoV-1 survivors.

The severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) survivors are more likely to produce a potent immune response to SARS-CoV-2 after booster vaccination. We assessed humoral and T cell responses against SARS-CoV-2 in previously vaccinated SARS-CoV-1 survivors and naïve healthy individuals (NHIs) after a booster Ad5-nCoV dose. Boosted SARS-CoV-1 survivors had a high neutralization of SARS-CoV-2 Wuhan-Hu-1 (WA1), Beta, and Delta but is limited to Omicron subvariants (BA.1, BA.2, BA.2.12.1, and BA.4/BA.5). Most boosted SARS-CoV-1 survivors had robust SARS-CoV-2-specific CD4+ and CD8+ T cell responses. While booster vaccination in NHIs elicited less or ineffective neutralization of WA1, Beta, and Delta, and none of them induced neutralizing antibodies against Omicron subvariants. However, they developed comparable SARS-CoV-2-specific T cell responses compared to boosted SARS-CoV-1 survivors. These findings suggest that boosted Ad5-nCoV would not elicit effective neutralizing antibodies against Omicron subvariants in SARS-CoV-1 survivors and NHIs but induced comparable robust T cell responses. Achieving a high antibody titer in SARS-CoV-1 survivors and NHIs is desirable to generate broad neutralization.

Spinal Microglia and Astrocytes: Two Key Players in Chronic Visceral Pain Pathogenesis.

Chronic visceral pain (CVP) is one of the common symptoms of many diseases triggered by underlying diseases of the internal organs of the human body. Its causes include vascular mechanisms, mechanical factors, persistent inflammation, and unexplained functional mechanisms. Although the pathogenesis is unclear, more and more research has begun to shift from the neuronal aspect to the glial cells in recent years. Some data highlight that the spinal glial cells, particularly the microglia and astrocytes, play an essential role in CVP. Based on this, we highlight the mechanisms of microglia and astrocytes in CVP concerning the release of cytokines, chemokines, and neuroactive substances and alterations in intracellular signaling pathways during the process. Finally, because CVP is widespread in various diseases, we present future perspectives targeting microglia and astrocytes for treatment.

The illness experience for people with amyotrophic lateral sclerosis: A qualitative study.

AIMS AND OBJECTIVES: This study aims to gain a comprehensive understanding of the illness experience of amyotrophic lateral sclerosis (ALS) patients in China and the meaning they attach to those experiences. BACKGROUND: ALS is a progressive and fatal neurodegenerative disorder that significantly impacts individuals and families. There is a large number of patients with ALS in China. However, little is known about how they live with ALS. DESIGN: Phenomenological qualitative research was performed among twenty people with ALS from the neurology department of a tertiary hospital in China. Colaizzi's method was used to analyse the participants' data. The Consolidated Criteria for Reporting Qualitative Research (COREQ) was used as a guideline to secure accurate and complete reporting of the study. RESULTS: We proposed three themes and eight subthemes on the illness experience of participants: (1) life countdown: 'my body was frozen' (body out of control and inward suffering); (2) family self-help: 'we kept an eye on each other' (family warmth and hardship, and supporting the supporter); and (3) reconstruction of life: 'what was the meaning of my life' (learning to accept, rebuilding self-worth, resetting the priority list and living in the moment). CONCLUSIONS: In the family self-help model, patients are prompted to turn from negative mentalities to search for meaning in life actively. Healthcare providers need to attach importance to the family self-help model to alleviate the pressure on medical resources. RELEVANCE TO CLINICAL PRACTICE: Healthcare providers should encourage patients to play a supportive role in the family and provide more care support and professional care knowledge guidance to caregivers, to promote the formation of the family self-help model which might help to improve the experience of patients and families.

Qiliqiangxin Rescues Mouse Cardiac Function by Regulating AGTR1/TRPV1-Mediated Autophagy in STZ-Induced Diabetes Mellitus.

BACKGROUND/AIMS: To explore the potential role of qiliqiangxin (QLQX) A traditional Chinese medicine and the involvement of angiotensin II receptor type 1 (AGTR1) and transient receptor potential vanilloid 1 (TRPV1) in diabetic mouse cardiac function. METHODS: Intragastric QLQX was administered for 5 weeks after streptozotocin (STZ) treatment. Additionally, Intraperitoneal injections of angiotensin II (Ang II) or intragastric losartan (Los) were administered to assess the activities of AGTR1 and TRPV1. Two-dimensional echocardiography and tissue histopathology were used to assess cardiac function Western blot was used to detect the autophagic biomarkers Such as light chain 3 P62 and lysosomal-associated membrane protein 2 And transmission electron microscopy was used to count the number of autophagosomes. RESULTS: Decreased expression of TRPV1 and autophagic hallmarks and reduced numbers of autophagolysosomes as well as increased expression of angiotensin converting enzyme 1 and AGTR1 were observed in diabetic hearts. Blocking AGTR1 with Los mimicked the QLQX-mediated improvements in cardiac function Alleviated myocardial fibrosis and enabled autophagy Whereas Ang II abolished the beneficial effects of QLQX in wild type diabetic mice but not in TRPV1-/- diabetic mice. CONCLUSIONS: QLQX may improve diabetic cardiac function by regulating AGTR1/ TRPV1-mediated autophagy in STZ-induced diabetic mice.

[Free grafting of internal preputial lamina for penile divided nevus in children].

OBJECTIVE: To evaluate the effect of free grafting of internal preputial lamina in the treatment of penile divided nevus in children. METHODS: This retrospective study included 5 children with penile divided nevus, 4 complicated by redundant prepuce and the other 1 by concealed penis, all treated by free grafting of internal preputial lamina from October 2015 to November 2017. The patients ranged in age from 6 years and 8 months to 10 years and 4 months, averaging 8 years and 6 months. The surgical procedure involved complete excision of the lesions underneath the foreskin with a safety margin of 2 mm, collection of healthy internal preputial lamina for free grafting onto the defected glans, and simultaneously circumcision or concealed penis correction. The removed tissue of the divided nevus was subjected to pathological examination. The patients were followed up for 4－29 (mean 18) months postoperatively. RESULTS: All incisions healed primarily and the free grafts of internal preputial lamina survived well, similar to the glans in color and with a desirable appearance. The patients lost no protopathic sensibility of the glans and experienced no recurrence. Pathological examination confirmed 1 case of intradermal nevus and 4 cases of compound nevus. CONCLUSIONS: Free grafting of internal preputial lamina is an ideal method for the treatment of penile divided nevus in children, with the advantages of easy graft collection, little color difference between the graft and surrounding skin, desirable external appearance, and definite clinical effect.

[Identification and Fermentation Optimization of an Endophytic Fungus BLH34 with Antibacterial Activity from Macleaya cordata].

Objective: To identify an endophytic fungus BLH34 isolated from the leaf of Macleaya cordata with antibacterial activity,and to optimize its fermentation medium. Methods: Antimicrobial activity of an endophytic fungus BLH34 was determined by the cylinder plate method. The morphological characteristics and internal transcribed spacer（ ITS） sequence were analyzed to identify the taxonomic position of the strain BLH34. The culture medium recipe was optimized by single factor and orthogonal experiment. Results: The results showed that the strain BLH34 had antimicrobial activity to the test strains,especially it showed significant inhibitory effect on Staphylococcus aureus. The strain BLH34 was identified as Penicillium turbatum,and the best culture medium recipe could be recognized as follows: 5% soluble starch,4% peptone,0. 06% NaNO3,and 0. 012% MgSO4·7H2O. Conclusion: The antimicrobial activity of crude extract was significantly increased after optimization, which could provide a basis for further separation and purification of the antibacterial substances extracted from strain BLH34.

[Clinical efficacy of different doses of gamma globulin combined with glucocorticoid in treatment of moderate/severe acute Guillain-Barré syndrome in children: a comparative analysis].

OBJECTIVE: To investigate the clinical efficacy and safety of intravenous injection of low-dose versus high-dose gamma globulin combined with glucocorticoid pulse therapy in the treatment of children with moderate/severe acute Guillain-Barré syndrome (GBS). METHODS: A total of 100 children with moderate/severe acute GBS were randomly assigned to low-dose group (n=48) and high-dose group (n=52). The children in the low-dose and high-dose groups were treated with 0.2 g/(kg · d) and 0.4 g/(kg · d) gamma globulin respectively combined with methylprednisolone. The two groups were compared in terms of the time to improvements of symptoms after treatment, serum levels of inflammatory factors, proportion of children undergoing invasive ventilation, treatment response rate, and adverse events. RESULTS: After 5 days of treatment, the low- and high-dose groups had significant reductions in serum levels of tumor necrosis factor-α, interleukin-6, and C-reactive protein, and there were no significant differences in the reductions of these markers between the two groups. There were no significant differences between the two groups in the time to recovery of respiratory muscle paralysis, time to an improvement in muscle strength of one grade, time to recovery of sensory disturbance, and length of hospital stay. There was no significant difference in the treatment response rate between the low- and high-dose groups (90% vs 92%). There were also no significant differences in the incidence rates of pyrexia, headache, nausea, and palpitation between the two groups. CONCLUSIONS: Low-dose versus high-dose gamma globulin combined with methylprednisolone pulse therapy have comparable clinical efficacy and safety in the treatment of children with moderate/severe acute GBS.

[Isolation of Actinomycete DF02 from Composting and Its Application in Biological Control of Botrytis cinerea].

OBJECTIVE: To isolate and identify the biocontrol actinomycete from composting, and to investigate its potted control effect against Botrytis cinerea. METHODS: Actinomycetes were isolated from composting by pour plate method. Inhibitory activities of acti- nomycetes were determined by dilution plate method and cylinder plate method. Strain with high activities was identified based on mor- phology and biochemical characterization and 16S rDNA gene sequence analysis. And its potted control effect was also investigated. RESULTS: 31 strains of actinomycetes were isolated, three of them had inhibitory effects on the test strains. Of which, the strain DF02 showed antagonistic to five plant pathogenic fungi of all the tested strains, and its inhibitory effect on Botrytis cinerea was the strongest. The results of potted control effect test showed that the protective and therapeutic efficacy of the fermentation suspension to Botrytis cinerea was 58.47% and 53.83%, respectively. According to taxonomic identification, the strain DF02 was identified as Strepto- myces neopeptinius. CONCLUSION: Strain DF02 is a biocontrol actinomycete with broad development potential, and these results provide ex- perimental basis for the biocontrol of Botrytis cinerea.

[Isolation and antimicrobial activities of actinomycetes from vermicompost].

In this paper, actinomycetes were isolated from vermicompost by tablet coating method. Antimicrobial activities of actinomycetes were measured by the agar block method. Strains with high activity were identified based on morphology and biochemical characteristics, as well as 16S rDNA gene sequence analysis. The results showed that 26 strains of actinomycetes were isolated, 16 of them had antimicrobial activities to the test strains which accounts for 61.54% of all strains. Among the 16 strains, the strain QYF12 and QYF22 had higher antimicrobial activity to Micrococcus luteus, with a formed inhibition zone of 27 mm and 31 mm, respectively. While the strain QYF26 had higher antimicrobial activity to Bacillus subtilis, and the inhibition zone diameter was 21 mm. Based on the identification of strains with high activity, the strain QYF12 was identified as Streptomyces chartreusis, the strain QYF22 was S. ossamyceticus and the strain QYF26 was S. gancidicus. This study provided a theoretical basis for further separate antibacterial product used for biological control.

Detection of antibodies against customized epitope: use of a coating antigen employing VEGF as fusion partner.

Diagnosis of many infectious, autoimmune diseases and cancers depends on the detection of specific antibodies against peptide epitope by enzyme-linked immunosorbent assay (ELISA). However, small peptides are difficult to be coated on the plate surfaces. In this study, we selected GnRH as a model hapten to evaluate whether VEGF121 would be suitable as an irrelevant hapten-carrier to develop a universal platform for specific antibodies detection. Firstly, GnRH was fused to the C terminus of VEGF121 and the resultant fusion protein VEGF-GnRH expressed effectively as inclusion bodies in Escherichia coli. Thereafter, VEGF-GnRH was easily purified to near homogeneity with a yield of about 235 mg from 2.1 L induced culture. At last, VEGF-GnRH was used to perform ELISA and western blot, and our results suggested that VEGF-GnRH was capable of detecting anti-GnRH antibodies in sera both qualitatively and quantitatively. Indeed, previous studies of our laboratory had demonstrated that other fusion proteins such as VEGF-Aß10, VEGF-GRP, VEGF-CETPC, and VEGF-ßhCGCTP37 were able to detect their corresponding antibodies specifically. Therefore, VEGF121 may be a suitable irrelevant fusion partner of important diagnostic peptide markers. Our works would shed some light on the development of a universal platform for detection of specific antibodies.

An endophytic sanguinarine-producing fungus from Macleaya cordata, Fusarium proliferatum BLH51.

Fermentation processes using sanguinarine-producing fungi other than Macleaya cordata may be an alternative way to produce sanguinarine (SA), which is a quaternary benzo[c]phenanthridine alkaloid possessing antibacterial, anthelmintic, and anti-inflammatory properties. In this study, a SA-producing endophytic fungus strain BLH51 was isolated from the leaves of M. cordata grown in the Dabie Mountain, China. Strain BLH51 produced SA when grown in potato dextrose liquid medium. The amount of SA produced by this endophytic fungus was quantified to be 178 µg/L by HPLC, substantially lower than that produced by the host tissue. The fungal SA--which was analyzed by thin layer chromatography and high-performance liquid chromatography--was shown to be identical to authentic SA. Strain BLH51 was identified as Fusarium proliferatum based on the morphological characteristics and nuclear ribosomal DNA ITS sequence analysis. To the best of our knowledge, this is the first report concerning the isolation and identification of endophytic SA-producing fungi from the host plant, which further proved that endophytic fungi are valuable reservoirs of bioactive compounds.

Roles of non-coding RNA in pancreatic islet development and functioning.

Non-coding RNA is a kind of non-coding protein RNA which is widely present in most of the organisms. Non-coding RNA plays key roles in the embryonic development,cell fate determination,and growth control in the living organisms. MicroRNA and long non-coding RNA involve in differentiation of endocrine cell,insulin gene expression and secretion,and insulin resistance,which are closely associated with diabetes.

[Effect of (E)-2-(4-bromophenyl )-1-(3,4-dihydroxyphenyl )ethanone oxime on proliferation and activation of mice lymphocytes].

OBJECTIVE: To study the effects of (E)-2-(4-bromophenyl)-1-(3, 4-dihydroxyphenyl) ethanone oxime (BDEO) on the proliferation and activation of the mice' s splenic lymphocytes and the peripheral blood lymphocytes induced by Concanavalin A (Con A) in vitro and in vivo, and its molecular mechanism. METHODS: During the lymphocyte proliferation and activation induced by Con A in vitro, MTT and cell counting were used to detect the transformation rates and survival rates of lymphocytes, and ELISA was used to measure the activity of caspase-9; moreover, the levels of Bax, Bcl-2 and caspase-3 were determined by Western blot, in order to observe the effects of BDEO on cell proliferation and activation. The effects of administration of Con A [15 mg/(kg x d)] and BDEO [(3, 6 mg/(kg x d)] by intraperitoneal injection on transformation rates of spleen cells and peripheral blood lymphocyte, as well as phagocytosis rate of peritoneal macrophages in mice were also observed in vivo. RESULTS: 0.3-1 micromol/L BDEO significantly inhibited the transformation rates and growth of mice lymphocyte (P < 0.05). The activity of caspase-9 and the levels of mitochondrial pro-apoptotic protein Bax and Bak gradually increased, then decreased as the BDEO continually accumulated. Anti-apoptotic protein Bcl-2 as well as mitochondrial Cyt C levels first decreased then increased gradually, and cytoplasmic Cyt C, cleaved caspase-9 and cleaved caspase-3 levels showed firstly a increase, then decrease gradually. Additionally, administration of BDEO by intraperitoneal injection significantly inhibited proliferation of spleen lymphocytes and peripheral blood lymphocyte, as well as phagocytosis of peritoneal macrophagesin in mice. CONCLUSION: BDEO might regulate the proliferation and activation of lymphocytes through activation of caspase-3 mainly via a mitochondrial intrinsic pathway; the inhibiting effect on the proliferation and transformation rate of lymphocytes was significant when the concentration of BDEO was relatively low; as the concentration accumulated increasingly, the inhibiting effect reduced. The results indicated that BDEO has immunosuppressive activity.

[Isolation and identification of an antimicrobial endophytic actinomycete from Macleaya cordata].

OBJECTIVE: An antimicrobial endophytic actinomycete strain was isolated from the root of Macleaya cordata, and its phylogenetic position was also investigated. METHODS: Endophytic actinomycetes were isolated from the root of Macleaya cordata growing in Dabie Mountain by tablet coating method. Antimicrobial activities of endophytic actinomycetes were determined by the agar block method,and then a potential strain was identified by morphology, biochemical characterization and molecular methods. RESULTS: A total of 15 strains of endophytic actinomycetes were isolated from the samples, six of them had antimicrobial activity to the test strains which accounts for 40% of all strains. Among the six strains,the strain BL7 was found to produce antibiotic substances which showed significant inhibitory effects on Staphylococcus aureus and Bacillus subtilis,with a formed inhibition zone of 29 mm and 20 mm respectively. Based on the morphology, biochemical characterization and 16S rDNA sequence analysis,the strain BL7 was preliminary identified as Streptomyces mobaraensis. CONCLUSION: Some members of Streptomyces genus have a very wide application prospect in medicine. This is the first report that Streptomyces mobaraensis strain was isolated from Macleaya cordata, and this study provides basis for the further exploration of the strain.

[Isolation of endophytic fungi from Macleaya cordata and screening of sanguinarine-producing strains].

Endophytic fungi were isolated from Macleaya cordata growing in Dabie Mountain by agar-block method, and then the endophytic fungi were grouped into different types based on their morphological characteristics, and thin layer chromatography (TLC) and high performance liquid chromatography (HPLC) were employed to determine whether the metabolic substances contained sanguinarine or not, and then preliminarily identified by morphological method. The results showed that the leaves hosted the largest number of endophytes (96 isolates) followed by the stems (57 isolates) and finally the roots (28 isolates), respectively. Based on morphological characteristics the endophytic fungi were grouped into 26 types in our study. TLC and HPLC results showed that there was sanguinarine in the metabolic substances of BLH 51 strain. According to the morphological characteristic, the BLH 51 strain was identified as Fusarium proliferatum. All these indicated that the medicinal plant M. cordata harbors abundant endophytes, which could be a new source for the search of active secondary metabolites.

Oncogenic and immunological role of EDIL3 in human tumours: From pan-cancer analysis to validation in gastric cancer.

Background: Epidermal growth factor-like repeats and discoidin I-like domains 3 (EDIL3) is a secreted extracellular matrix protein implicated in diverse physiological and pathological processes including embryonic development, angiogenesis, and anti-inflammatory responses. Recent reports have indicated that EDIL3 play critical roles in carcinogenesis and progression of many cancers. Herein, we performed a pan-cancer investigation to study the potential functions of EDIL3 in various cancers and experimentally validate its function in gastric cancer (GC). Methods: We analysed EDIL3 expression profiles in different tumours using The Cancer Genome Atlas database. The Kaplan-Meier Plotter was used to investigate the prognostic value of EDIL3, while receiver operating characteristic curve was performed to analyze its diagnostic efficacy. Several bioinformatics tools were used to study the association between EDIL3 and promoter methylation, gene enrichment analysis, immune infiltration, immune-related genes, and drug sensitivity. Molecular biology experiments were conducted to validate the tumorigenic effects of EDIL3. Results: EDIL3 is variably expressed in different cancers and is closely associated with clinical outcomes. An inverse correlation between EDIL3 and DNA methylation has been observed in 13 cancers. Enrichment analysis indicated that EDIL3 is correlated with many cellular pathways such as extracellular matrix receptor interactions and focal adhesion. EDIL3 was tightly associated with immune infiltration and immune checkpoints. EDIL3 knockdown can promote GC calls apoptosis while preventing proliferation, migration, and invasion in vitro. Conclusion: EDIL3 is a promising prognostic, diagnostic, and immunological biomarker in various cancers, which could be applied as a new target for cancer therapy.

Variant-specific antibody response following repeated SARS-CoV-2 vaccination and infection.

The ongoing emergence of SARS-CoV-2 variants poses challenges to the immunity induced by infections and vaccination. We conduct a 6-month longitudinal evaluation of antibody binding and neutralization of sera from individuals with six different combinations of vaccination and infection against BA.5, XBB.1.5, EG.5.1, and BA.2.86. We find that most individuals produce spike-binding IgG or neutralizing antibodies against BA.5, XBB.1.5, EG.5.1, and BA.2.86 2 months after infection or vaccination. However, compared to ancestral strain and BA.5 variant, XBB.1.5, EG.5.1, and BA.2.86 exhibit comparable but significant immune evasion. The spike-binding IgG and neutralizing antibody titers decrease in individuals without additional antigen exposure, and <50% of individuals neutralize XBB.1.5, EG.5.1, and BA.2.86 during the 6-month follow-up. Approximately 57% of the 107 followed up individuals experienced an additional infection, leading to improved binding IgG and neutralizing antibody levels against these variants. These findings provide insights into the impact of SARS-CoV-2 variants on immunity following repeated exposure.

RNA-binding protein CPSF6 regulates IBSP to affect pyroptosis in gastric cancer.

BACKGROUND: Extensive evidence has illustrated the promotive role of integrin binding sialoprotein (IBSP) in the progression of multiple cancers. However, little is known about the functions of IBSP in gastric cancer (GC) progression. AIM: To investigate the mechanism underlying the regulatory effects of IBSP in GC progression, and the relationship between IBSP and cleavage and polyadenylation factor 6 (CPSF6) in this process. METHODS: The mRNA and protein expression of relevant genes were assessed through real-time quantitative polymerase chain reaction and Western blot, respectively. Cell viability was evaluated by Cell Counting Kit-8 assay. Cell invasion and migration were evaluated by Transwell assay. Pyroptosis was measured by flow cytometry. The binding between CPSF6 and IBSP was confirmed by luciferase reporter and RNA immunoprecipitation (RIP) assays. RESULTS: IBSP exhibited higher expression in GC tissues and cell lines than in normal tissues and cell lines. IBSP knockdown suppressed cell proliferation, migration, and invasion but facilitated pyroptosis. In the exploration of the regulatory mechanism of IBSP, potential RNA binding proteins for IBSP were screened with catRAPID omics v2.0. The RNA-binding protein CPSF6 was selected due to its higher expression in stomach adenocarcinoma. Luciferase reporter and RIP assays revealed that CPSF6 binds to the 3'-untranslated region of IBSP and regulates its expression. Knockdown of CPSF6 inhibited cell proliferation, migration, and invasion but boosted pyroptosis. Through rescue assays, it was uncovered that the retarded GC progression mediated by CPSF6 knockdown was reversed by IBSP overexpression. CONCLUSION: Our study highlighted the vital role of the CPSF6/IBSP axis in GC, suggesting that IBSP might be an effective bio-target for GC treatment.

A novel synthesized prodrug of gemcitabine based on oxygen-free radical sensitivity inhibited the growth of lung cancer cells.

In the present study, we introduced the H 2O 2-sensitive thiazolidinone moiety at the 4th amino group of gemcitabine (GEM) to synthesize a new target compound named GEM-ZZQ, and then we confirmed its chemical structure by nuclear magnetic resonance spectroscopy. We further confirmed that GEM-ZZQ had a good chemical stability in different pH solutions in vitro and that it could be activated by H 2O 2 to release GEM. Pharmacodynamic studies revealed that the growth inhibition of human normal epithelial cells was weaker by GEM-ZZQ than by GEM treatment and that the inhibition of various lung cancer cell lines by GEM-ZZQ was similar to that of GEM. For the lung cancer cell lines that are resistant to the epidermal growth factor receptor (EGFR)-targeting inhibitor osimertinib, GEM-ZZQ showed less growth inhibition than GEM; however, GEM-ZZQ in combination with cisplatin showed better synergistic effects than GEM in the low-dose groups. In summary, we provided a new anti-cancer compound GEM-ZZQ for treating lung cancer by modifying the GEM structure.