Comprehensive analysis of KLF family reveals KLF6 as a promising prognostic and immune biomarker in pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest tumors worldwide, with extremely aggressive and complicated biology. Krüppel-like factors (KLFs) encode a series of transcriptional regulatory proteins and play crucial roles in a variety of processes, including tumor cell differentiation and proliferation. However, the potential biological functions and possible pathways of KLFs in the progression of PDAC remain elusive. METHODS: We systematically evaluated the transcriptional variations and expression patterns of KLFs in pancreatic cancer from the UCSC Xena. Based on difference analysis, the non-negative matrix factorization (NMF) algorithm was utilized to identify the immune characteristics and clinical significance of two different subtypes. The multivariate Cox regression was used to construct the risk model and then explore the differences in tumor immune microenvironment (TIME) and drug sensitivity between high and low groups. Through single-cell RNA sequencing (scRNA-seq) analysis, we screened KLF6 and further investigated its biological functions in pancreatic cancer and pan-cancer. RESULTS: The KLFs exhibited differential expression and mutations in the transcriptomic profile of PDAC. According to the expression of KLFs, patients were classified into two distinct subtypes, each exhibiting significant differences in prognosis and TIME. Moreover, the KLF signature was developed using univariate Cox and Lasso regression, which proved to be a reliable and effective prognostic model. Furthermore, the KLF_Score was closely associated with immune infiltration, response to immunotherapy, and drug sensitivity and we screened small molecule compounds targeting prognostic genes separately. Through scRNA-seq analysis, KLF6 was selected to further demonstrate its role in the malignance of PC in vitro. Finally, pan-cancer analysis emphasized the biological significance of KLF6 in multiple types of tumors and its clinical utility in assessing cancer prognosis. CONCLUSION: This study elucidated the pivotal role of KLF family genes in the malignant development of PC through comprehensive analysis and revealed that KLF6 would be a novel diagnostic biomolecule marker and potential therapeutic target for PDAC.

Prospective observational study on biomarkers of response in pancreatic ductal adenocarcinoma.

Adjuvant chemotherapy benefits patients with resected pancreatic ductal adenocarcinoma (PDAC), but the compromised physical state of post-operative patients can hinder compliance. Biomarkers that identify candidates for prompt adjuvant therapy are needed. In this prospective observational study, 1,171 patients with PDAC who underwent pancreatectomy were enrolled and extensively followed-up. Proteomic profiling of 191 patient samples unveiled clinically relevant functional protein modules. A proteomics-level prognostic risk model was established for PDAC, with its utility further validated using a publicly available external cohort. More importantly, through an interaction effect regression analysis leveraging both clinical and proteomic datasets, we discovered two biomarkers (NDUFB8 and CEMIP2), indicative of the overall sensitivity of patients with PDAC to adjuvant chemotherapy. The biomarkers were validated through immunohistochemistry on an internal cohort of 386 patients. Rigorous validation extended to two external multicentic cohorts-a French multicentric cohort (230 patients) and a cohort from two grade-A tertiary hospitals in China (466 patients)-enhancing the robustness and generalizability of our findings. Moreover, experimental validation through functional assays was conducted on PDAC cell lines and patient-derived organoids. In summary, our cohort-scale integration of clinical and proteomic data demonstrates the potential of proteomics-guided prognosis and biomarker-aided adjuvant chemotherapy for PDAC.

BHLHE40 Inhibits Ferroptosis in Pancreatic Cancer Cells via Upregulating SREBF1.

Pancreatic cancer (PCa) is one of the most fatal human malignancies. The enhanced infiltration of stromal tissue into the PCa tumor microenvironment limits the identification of key tumor-specific transcription factors and epigenomic abnormalities in malignant epithelial cells. Integrated transcriptome and epigenetic multiomics analyses of the paired PCa organoids indicate that the basic helix-loop-helix transcription factor 40 (BHLHE40) is significantly upregulated in tumor samples. Increased chromatin accessibility at the promoter region and enhanced mTOR pathway activity contribute to the elevated expression of BHLHE40. Integrated analysis of chromatin immunoprecipitation-seq, RNA-seq, and high-throughput chromosome conformation capture data, together with chromosome conformation capture assays, indicate that BHLHE40 not only regulates sterol regulatory element-binding factor 1 (SREBF1) transcription as a classic transcription factor but also links the enhancer and promoter regions of SREBF1. It is found that the BHLHE40-SREBF1-stearoyl-CoA desaturase axis protects PCa cells from ferroptosis, resulting in the reduced accumulation of lipid peroxidation. Moreover, fatostatin, an SREBF1 inhibitor, significantly suppresses the growth of PCa tumors with high expressions of BHLHE40. This study highlights the important roles of BHLHE40-mediated lipid peroxidation in inducing ferroptosis in PCa cells and provides a novel mechanism underlying SREBF1 overexpression in PCa.

Therapeutic effect of hydrogen and its mechanisms in kidney disease treatment.

Hydrogen is a simple, colorless, and biologically active small molecule gas that can react with reactive oxygen species. Recent research suggests that hydrogen possesses several biological effects, including antioxidant, anti-inflammatory, and anti-apoptotic effects, while exhibiting an extremely high level of safety. Hydrogen application has shown promise in treating a range of acute and chronic diseases, both benign and malignant. Importantly, an increasing number of clinical studies on hydrogen have demonstrated its efficacy and safety in treating various diseases. This review highlights the beneficial effects of hydrogen in kidney diseases, summarizes potential mechanisms by which hydrogen may act in these diseases, and proposes several promising avenues for future research.

Thorough Optimization for Intrinsically Stretchable Organic Photovoltaics.

The development of intrinsically stretchable organic photovoltaics (is-OPVs) with a high efficiency is of significance for practical application. However, their efficiencies lag far behind those of rigid or even flexible counterparts. To address this issue, an advanced top-illuminated OPV is designed and fabricated, which is intrinsically stretchable and has a high performance, through systematic optimizations from material to device. First, the stretchability of the active layer is largely increased by adding a low-elastic-modulus elastomer of styrene-ethylene-propylene-styrene tri-block copolymer (SEPS). Second, the stretchability and conductivity of the opaque electrode are enhanced by a conductive polymer/metal (denoted as M-PH1000@Ag) composite electrode strategy. Third, the optical and electrical properties of a sliver nanowire transparent electrode are improved by a solvent vapor annealing strategy. High-performance is-OPVs are successfully fabricated with a top-illuminated structure, which provides a record-high efficiency of 16.23%. Additionally, by incorporating 5-10% elastomer, a balance between the efficiency and stretchability of the is-OPVs is achieved. This study provides valuable insights into material and device optimizations for high-efficiency is-OPVs, with a low-cost production and excellent stretchability, which indicates a high potential for future applications of OPVs.

Exploring the adaptive leisure activities of classified nursing model in elderly colon cancer patients: a perspective on interactive care.

OBJECTIVE: The aims of the study were first to explore the adaptive leisure activities of classified nursing model from the perspective of nurse-patient interactive care, and to explore its impact on the physical and mental health of patients with colon cancer. METHODS: From September 2017 to March 2022 as the observation time node, 82 patients with colon cancer who met the established inclusion and exclusion criteria were regarded as the research objects through the random number table as the grouping tool. The two groups of patients were named as the research group and the control group, with 41 patients in each group. The control group implemented routine nursing measures, and the research group implemented classified nursing mode and adaptive leisure activity mode. The two groups of patients received 4 weeks of nursing intervention. With the help of self-rating anxiety scale, self-rating depression scale, self-care ability evaluation scale and health status survey brief form, the two groups of patients were compared before intervention and at the end of the 4th week after intervention. RESULTS: After the intervention, the anxiety score (t = 6.656, p < 0.001) and depression score (t = 4.851, p < 0.001) of the research group were lower than those of the control group, and the difference was statistically significant. After the intervention, the self-concept (t = 4.845, p < 0.001), self-responsibility (t = 6.071, p < 0.001), self-care skills (t = 3.341, p < 0.001), health knowledge (t = 3.698, p < 0.001) and total score (t = 9.246, p < 0.001) of the research group were higher than those of the control group, and the difference was statistically significant. After the intervention, physical functioning (t = 8.141, p < 0.001), bodily pain (t = 6.083, p < 0.001), general health (t = 9.424, p < 0.001), role-physical (t = 8.057, p < 0.001), role-emotional (t = 13.252, p < 0.001), mental health (t = 12.565, p < 0.001), social functioning (t = 10.813, p < 0.001) and vitality score (t = 12.890, p < 0.001) of the research group were higher than those of the control group, with significant differences. CONCLUSION: Interactive care through adaptive leisure nursing improves mental well-being, self-management, and psychosocial functioning in elderly colon cancer patients, promoting overall health.

The genomic and immune landscapes of gastric cancer and their correlations with HER2 amplification and PD-L1 expression.

BACKGROUND: Anti-PD1/PD-L1 antibody plus human epidermal growth factor receptor 2 (HER2) antibody and chemotherapy have become the new first-line therapy for HER2 overexpression-positive advanced gastric cancers (GC), suggesting that HER2 and PD-L1 play a vital role in guiding systemic treatment for patients with GC. This study aimed to depict the genomic and immune landscapes of Chinese patients with GC and investigate their correlations with HER2 amplification and PD-L1 expression. PATIENTS AND METHODS: Next-generation targeted sequencing and PD-L1 immunohistochemistry were performed on tumor samples from 735 patients with pathologically diagnosed GC. The genomic and immune landscapes and their correlations with HER2 amplification and PD-L1 expression were analyzed. RESULTS: The most commonly mutated genes in Chinese GC were TP53 (64%), CDH1 (20%), ARID1A (18%), HMCN1 (15%), KMT2D (11%), and PIK3CA (11%). Seventy-six (10%) patients were HER2 amplification, and 291 (40%) had positive PD-L1 expression. Classifying the total population based on HER2 amplification and PD-L1 expression level, 735 patients were divided into four subgroups: HER2+/PD-L1+ (4.5%), HER2+/PD-L1- (5.9%), HER2-/PD-L1+ (35.1%), and HER2-/PD-L1- (54.5%). The HER2+/PD-L1- and HER2+/PD-L1+ subgroups exhibited dramatically higher rate of TP53 mutations, CCNE1 and VEGF amplifications. The HER2+/PD-L1- subgroup also had a markedly higher rate of MYC amplification and KRAS mutations. The HER2-/PD-L1+ subgroup had significantly higher rate of PIK3CA mutations. HER2+/PD-L1- subgroup had the highest TMB level and HER2-/PD-L1+ subgroup had the highest proportion of patients with microsatellite instability-high than other subgroups. Furthermore, we observed that different HER2 amplification levels had distinct impacts on the correlations between PD-L1 expression and therapeutic genomic alterations, but no impact on the prognosis. CONCLUSION: The combination of HER2 amplification and PD-L1 expression in Chinese patients with GC could stratify the total populations into several subgroups with distinctive genomic and immune landscapes, which should be considered when making personalized treatment decisions.

High CTCF expression mediated by FGD5-AS1/miR-19a-3p axis is associated with immunosuppression and pancreatic cancer progression.

The most common reason for cancer-related death globally is predicted to be pancreatic cancer (PC), one of the deadliest cancers. The CCCTC-binding factor (CTCF) regulates the three-dimensional structure of chromatin, was reported to be highly regulated in various malignancies. However, the underlying biological functions and possible pathways via which CTCF promotes PC progression remain unclear. Herein, we examined the CTCF function in PC and discovered that CTCF expression in PC tissues was significantly raised compared to neighboring healthy tissues. Additionally, Kaplan-Meier survival analysis demonstrated a strong connection between elevated CTCF expression and poor patient prognosis. A study of the ROC curve (receiver operating characteristic) revealed an AUC value for CTCF of 0.968. Subsequent correlation analysis exhibited a strong relationship between immunosuppression and CTCF expression in PC. CTCF knockdown significantly inhibited the malignant biological process of PC in vitro and in vivo, suggesting that CTCF may be a potential PC treatment target. We also identified the FGD5 antisense RNA 1 (FGD5-AS1)/miR-19a-3p axis as a possible upstream mechanism for CTCF overexpression. In conclusion, our data suggest that ceRNA-mediated CTCF overexpression contributes to the suppression of anti-tumor immune responses in PC and could be a predictive biomarker and potential PC treatment target.

ATF3-induced activation of NF-κB pathway results in acquired PARP inhibitor resistance in pancreatic adenocarcinoma.

PURPOSE: Olaparib, an inhibitor of poly-(adenosine diphosphate-ribose) polymerase (PARP), has been shown to have anticancer benefits in patients with pancreatic cancer who have a germline mutation in BRCA1/2. However, resistance acquired on long-term exposure to olaparib significantly impedes clinical efficacy. METHODS: In this study, the chromatin accessibility and differentially expressed transcripts of parental and olaparib-resistant pancreatic cancer cell lines were assessed using the Assay for Transposase Accessible Chromatin with sequencing (ATAC-seq) and mRNA-seq. Detection of downstream genes regulated by transcription factors using ChIP (Chromatin immunoprecipitation assay). RESULTS: According to pathway enrichment analysis, differentially expressed genes in olaparib-resistant cells were remarkably enriched in the NF-κB signaling pathway. With ATAC-seq, we identified chromatin regions with higher accessibility in olaparib-resistant cells and predicted a series of important transcription factors. Among them, activating transcription factor 3 (ATF3) was significantly highly expressed. Functional experiments verified that inhibition of ATF3 suppressed the NF-κB pathway significantly and restored olaparib sensitivity in olaparib-resistant cells. CONCLUSION: Experiments in vitro and in vivo indicate ATF3 enhances olaparib resistance through the NF-κB signaling pathway, suggesting that ATF3 could be employed as an olaparib sensitivity and prognostic indicator in patients with pancreatic cancer.

LIPH contributes to glycolytic phenotype in pancreatic ductal adenocarcinoma by activating LPA/LPAR axis and maintaining ALDOA stability.

BACKGROUND: LIPH, a membrane-associated phosphatidic acid-selective phospholipase A1a, can produce LPA (Lysophosphatidic acid) from PA (Phosphatidic acid) on the outer leaflet of the plasma membrane. It is well known that LIPH dysfunction contributes to lipid metabolism disorder. Previous study shows that LIPH was found to be a potential gene related to poor prognosis with pancreatic ductal adenocarcinoma (PDAC). However, the biological functions of LIPH in PDAC remain unclear. METHODS: Cell viability assays were used to evaluate whether LIPH affected cell proliferation. RNA sequencing and immunoprecipitation showed that LIPH participates in tumor glycolysis by stimulating LPA/LPAR axis and maintaining aldolase A (ALDOA) stability in the cytosol. Subcutaneous, orthotopic xenograft models and patient-derived xenograft PDAC model were used to evaluate a newly developed Gemcitabine-based therapy. RESULTS: LIPH was significantly upregulated in PDAC and was related to later pathological stage and poor prognosis. LIPH downregulation in PDAC cells inhibited colony formation and proliferation. Mechanistically, LIPH triggered PI3K/AKT/HIF1A signaling via LPA/LPAR axis. LIPH also promoted glycolysis and de novo synthesis of glycerolipids by maintaining ALDOA stability in the cytosol. Xenograft models show that PDAC with high LIPH expression levels was sensitive to gemcitabine/ki16425/aldometanib therapy without causing discernible side effects. CONCLUSION: LIPH directly bridges PDAC cells and tumor microenvironment to facilitate aberrant aerobic glycolysis via activating LPA/LPAR axis and maintaining ALDOA stability, which provides an actionable gemcitabine-based combination therapy with limited side effects.

Hypoxia-induced long non-coding RNA LINC00460 promotes p53 mediated proliferation and metastasis of pancreatic cancer by regulating the miR-4689/UBE2V1 axis and sequestering USP10.

Long non-coding RNAs are considered to be key regulatory factors of oncogenesis and tumor progression. It is reported that LINC00460 plays the role of oncogene in some tumors. However, LINC00460's role and mechanism of action in pancreatic cancer have not yet been fully elucidated. We identified LINC00460 by analyzing data from the Gene Expression Omnibus database. The role of LINC00460 in proliferation and metastasis was examined using CCK8, colony formation, wound healing, and transwell assays. The potential mechanisms of LINC00460 in regulating mRNA levels were elucidated by RNA pull-down, RNA immunoprecipitation, Chromatin immunoprecipitation, Co-immunoprecipitation, and Immunofluorescence assays. The results showed that LINC00460 was upregulated in pancreatic cancer cells and tissues. Highly expressed LINC00460 is significantly related to short survival of pancreatic cancer patients. Inhibition of LINC00460 attenuated pancreatic cancer cell proliferation and metastasis, whereas its overexpression reversed this effect. Mechanically, LINC00460 is induced by hypoxia, through binding of the hypoxia-inducible factor 1-α in the promoter region of LINC00460. Furthermore, LINC00460 functioned as an miR-4689 sponge to regulate the downstream target gene UBE2V1, enhancing the stability of mutant p53 in pancreatic cancer cells. LINC00460 also further promotes pancreatic cancer development by sequestering USP10, a cytoplasmic ubiquitin-specific protease that deubiquitinates p53 and enhances its stability. Collectively, our study demonstrated that LINC00460 is a hypoxia-induced lncRNA that plays the role of oncogene in pancreatic cancer by modulating the miR-4689/UBE2V1 axis, sequestering USP10, and ultimately enhancing the stability of mutant p53.

BHLHE40, a potential immune therapy target, regulated by FGD5-AS1/miR-15a-5p in pancreatic cancer.

Pancreatic cancer, as one of the neoplasms with the highest degree of malignancy, has become a main disease of concerns in recent years. BHLHE40, a critical transcription factor for remodeling of the tumor immune microenvironment, has been described to be substantially increased in a variety of tumor-associated immune cells. Nevertheless, the pro-cancer biological functions and underlying molecular mechanisms of BHLHE40 for pancreatic cancer and its unique microenvironment are unclear. Hereby, we investigated the pro-oncogenic role of BHLHE40 in the pancreatic cancer microenvironment by bioinformatics analysis and cell biology experiments and determined that the expression of BHLHE40 was obviously elevated in pancreatic cancer tissues than in adjacent normal tissues. In parallel, Kaplan-Meier survival analysis unveiled that lower expression of BHLHE40 was strongly associated with better prognosis of patients. Receiver operating characteristic (ROC) curve analysis confirmed the accuracy of the BHLHE40-related prediction model. Subsequent, spearman correlation analysis observed that higher expression of BHLHE40 might be involved in immunosuppression of pancreatic cancer. Silencing of BHLHE40 could inhibit proliferation, invasion, and apoptosis of pancreatic cancer in vitro and in vivo, implying that BHLHE40 is expected to be a potential therapeutic target for pancreatic cancer. In addition, we explored and validated the FGD5-AS1/miR-15a-5p axis as a potential upstream regulatory mode for high expression of BHLHE40 in pancreatic cancer. In summary, our data showed that ceRNA involved in the regulation of BHLHE40 contributes to the promotion of immunosuppressive response in pancreatic and is expected to be a diagnostic marker and potential immunotherapeutic target for pancreatic cancer.

Enhancing prognostic accuracy in head and neck squamous cell carcinoma chemotherapy via a lipid metabolism-related clustered polygenic model.

OBJECTIVE: Systemic chemotherapy is the first-line therapeutic option for head and neck squamous cell carcinoma (HNSCC), but it often fails. This study aimed to develop an effective prognostic model for evaluating the therapeutic effects of systemic chemotherapy. METHODS: This study utilized CRISPR/cas9 whole gene loss-of-function library screening and data from The Cancer Genome Atlas (TCGA) HNSCC patients who have undergone systemic therapy to examine differentially expressed genes (DEGs). A lipid metabolism-related clustered polygenic model called the lipid metabolism related score (LMRS) model was established based on the identified functionally enriched DEGs. The prediction efficiency of the model for survival outcome, chemotherapy, and immunotherapy response was evaluated using HNSCC datasets, the GEO database and clinical samples. RESULTS: Screening results from the study demonstrated that genes those were differentially expressed were highly associated with lipid metabolism-related pathways, and patients receiving systemic therapy had significantly different prognoses based on lipid metabolism gene characteristics. The LMRS model, consisting of eight lipid metabolism-related genes, outperformed each lipid metabolism gene-based model in predicting outcome and drug response. Further validation of the LMRS model in HNSCCs confirmed its prognostic value. CONCLUSION: In conclusion, the LMRS polygenic prognostic model is helpful to assess outcome and drug response for HNSCCs and could assist in the timely selection of the appropriate treatment for HNSCC patients. This study provides important insights for improving systemic chemotherapy and enhancing patient outcomes.

Schwann cells regulate tumor cells and cancer-associated fibroblasts in the pancreatic ductal adenocarcinoma microenvironment.

Neuropathy is a feature more frequently observed in pancreatic ductal adenocarcinoma (PDAC) than other tumors. Schwann cells, the most prevalent cell type in peripheral nerves, migrate toward tumor cells and associate with poor prognosis in PDAC. To unveil the effects of Schwann cells on the neuro-stroma niche, here we perform single-cell RNA-sequencing and microarray-based spatial transcriptome analysis of PDAC tissues. Results suggest that Schwann cells may drive tumor cells and cancer-associated fibroblasts (CAFs) to more malignant subtypes: basal-like and inflammatory CAFs (iCAFs), respectively. Moreover, in vitro and in vivo assays demonstrate that Schwann cells enhance the proliferation and migration of PDAC cells via Midkine signaling and promote the switch of CAFs to iCAFs via interleukin-1α. Culture of tumor cells and CAFs with Schwann cells conditioned medium accelerates PDAC progression. Thus, we reveal that Schwann cells induce malignant subtypes of tumor cells and CAFs in the PDAC milieu.

Comprehensive machine learning-generated classifier identifies pro-metastatic characteristics and predicts individual treatment in pancreatic cancer: A multicenter cohort study based on super-enhancer profiling.

Rationale: Accumulating evidence illustrated that the reprogramming of the super-enhancers (SEs) landscape could promote the acquisition of metastatic features in pancreatic cancer (PC). Given the anatomy-based TNM staging is limited by the heterogeneous clinical outcomes in treatment, it is of great clinical significance to tailor individual stratification and to develop alternative therapeutic strategies for metastatic PC patients based on SEs. Methods: In our study, ChIP-Seq analysis for H3K27ac was performed in primary pancreatic tumors (PTs) and hepatic metastases (HMs). Bootstrapping and univariate Cox analysis were implemented to screen prognostic HM-acquired, SE-associated genes (HM-SE genes). Then, based on 1705 PC patients from 14 multicenter cohorts, 188 machine-learning (ML) algorithm integrations were utilized to develop a comprehensive super-enhancer-related metastatic (SEMet) classifier. Results: We established a novel SEMet classifier based on 38 prognostic HM-SE genes. Compared to other clinical traits and 33 published signatures, the SEMet classifier possessed robust and powerful performance in predicting prognosis. In addition, patients in the SEMetlow subgroup owned dismal survival rates, more frequent genomic alterations, and more activated cancer immunity cycle as well as better benefits in immunotherapy. Remarkably, there existed a tight correlation between the SEMetlow subgroup and metastatic phenotypes of PC. Among 18 SEMet genes, we demonstrated that E2F7 may promote PC metastasis through the upregulation of TGM2 and DKK1. Finally, after in silico screening of potential compounds targeted SEMet classifier, results revealed that flumethasone could enhance the sensitivity of metastatic PC to routine gemcitabine chemotherapy. Conclusion: Overall, our study provided new insights into personalized treatment approaches in the clinical management of metastatic PC patients.

Can Ivermectin kill Sarcoptes scabiei during the molting process?

BACKGROUND: Sarcoptes scabiei is a permanent obligate ectoparasite that lives and reproduces in the epidermis of humans and other mammals worldwide. There is a lack of information on the molting process of Sarcoptes scabiei. Ivermectin is widely used to treat Sarcoptes infection in humans and animals, while the survival of molting Sarcoptes mites in the presence of ivermectin is unknown. The aim of the present study is to investigate the molting process of Sarcoptes mites and assess the activity of ivermectin during the molting process of Sarcoptes mites. METHODOLOGY/PRINCIPAL FINDINGS: molting Sarcoptes mites were incubated at 35°C and 80% relative humidity and observed hourly until complete molt. Of the 192 molting mites recorded, the longest molt periods for larvae and nymphs were 23 and 30 h, respectively. The activity of ivermectin on molting Sarcoptes mites was also assessed using two concentrations of the drug (0.1 and 0.05 mg/ml). The exposure time for molting mites was determined by 100% mortality of female mites exposed to the solution of ivermectin. While all female mites were killed after exposure to 0.1 mg/ml ivermectin for 2 h and and 0.05 mg/ml for 7 h, 32% and 36% of molting mites survived and successfully molted, respectively. CONCLUSIONS/SIGNIFICANCE: The present study demonstrated that molting Sarcoptes mites are less susceptible to ivermectin than active mites. As a consequence, mites may survive after two doses of ivermectin given 7 days apart due not only to hatching eggs but also to the resistance of mites during their molting process. Our results provide insight into the optimal therapeutic regimens for scabies and highlight the need for further research on the molting process of Sarcoptes mites.