The clinical value of carbon nanoparticles in sentinel lymph node biopsy for early vulvar cancer.

Objective: Carbon nanoparticle (CNP)-guided sentinel lymph node biopsy (SLNB) has been extensively adopted as a cost-effective and highly efficient method for tracing malignant tumors except for those associated with vulvar cancer. The current study aimed to validate the feasibility and efficacy of CNPs in tracking sentinel lymph nodes (SLNs) in patients with early vulvar cancer. Methods: We retrospectively reviewed patients with vulvar cancer at our institution from January 2016 to April 2022 who were pathologically diagnosed and underwent SLNB or inguinofemoral lymphadenectomy (IFLND). CNPs were the only lymphatic tracer used in SLNB. Patient demographics, perioperative outcomes and follow-up results, including overall survival (OS) and progression-free survival (PFS), were compared between the SLNB and IFLND groups. Results: Data from 52 patients were collected and investigated. Forty groins of 22 patients who underwent SLNB with CNP tracing were included. Black-stained SLNs were detected in 32 groins of 19 patients, and the rates of CNP detection by patient and by groin were 86.4 % and 80 %, respectively. Patients who underwent SLNB had better perioperative outcomes than those who underwent IFLND in certain aspects (groin drainage rate: 41.2 % and 80 %, respectively, p < 0.05; daily drainage volume (ml): 12.49 and 36.4, respectively, p < 0.05; and inguinal wound healing rate: 100 % and 80 %, respectively, p < 0.05). The results of survival analysis indicated similar prognoses for node-negative patients who underwent CNP-guided SLNB or IFLND. Conclusions: Sentinel lymph node mapping with CNPs in vulvar cancer is feasible and demonstrates considerable biosecurity. With a satisfactory SLN detection rate achieved expediently, CNPs are a promising lymphatic tracer worthy of further utilization in vulvar cancer and could be an alternative option to canonical tracers.

Comparison of patient-controlled epidural analgesia and epidural morphine for post-cesarean section analgesia: experience from a tertiary center in China.

PURPOSE: To compare patient-controlled epidural analgesia (PCEA) and epidural morphine (EM) for post-cesarean section analgesia in real-world experience from China. METHODS: Parturients receiving one dose of EM (1-2 mg), PCEA, or both EM and PCEA from Peking Union Medical College Hospital were retrospectively recruited. Logistic models were used to identify risk factors. RESULTS: Of 1079 parturients enrolled, 919 (85.2%) parturients received only EM, 105 (9.7%) parturients received PCEA, and 55 (5.1%) parturients received both EM and PCEA. Significantly more parturients from EM group requested supplementary analgesia than those from PCEA and PCEA + EM group (583, 63.4% vs 52, 49.5% vs 25, 45.5%, P = 0.001) with more times of supplementary analgesia (1, IQR: 0-2 vs 0, IQR: 0-1 vs 0, IQR: 0-1 times, P < 0.001) and larger amounts of nonsteroidal anti-inflammatory drugs (NSAIDs) (50, IQR: 0-100 mg vs 0, IQR: 0-50 mg vs 0, IQR: 0-50 mg, P < 0.001). In multivariable Logistic regression for the supplementary analgesia risk, the application of PCEA (OR: 0.557, 95%CI 0.396-0.783, P = 0.001) and the use of NSAIDs intraoperatively (OR: 2.996, 95%CI 1.811-4.957, P < 0.001) were identified as independent predictors. A total of 1040 (96.4%) patients received prophylactic antiemetic therapy during surgery. Only 13 (1.2%) and 7 (0.6%) patients in our cohort requested antiemetic and antipruritic drugs, respectively. CONCLUSION: The use of PCEA was an independent protective factor for supplementary analgesia during the post-cesarean section. Prophylactic antiemetic therapy may reduce the side effects of post-cesarean analgesia.

Fabric structure and polymer composition as key contributors to micro(nano)plastic contamination in face masks.

The surge in face mask use due to COVID-19 has raised concerns about micro(nano)plastics (MNPs) from masks. Herein, focusing on fabric structure and polymer composition, we investigated MNP generation characteristics, mechanisms, and potential risks of surgical polypropylene (PP) and fashionable polyurethane (PU) masks during their wearing and photoaging based on stereomicroscope, µ-Fourier transform infrared spectroscopy (µ-FTIR), and scanning electron microscope (SEM) techniques. Compared with new PP and PU masks (66 ± 16 MPs/PP-mask, 163 ± 83 MPs/PU-mask), single- and multiple-used masks exhibited remarkably increased MP type and abundance (600-1867 MPs/PP-mask, 607-2167 MPs/PU-mask). Disinfection exacerbated endogenous MP generation in masks, with washing (416 MPs/PP-mask, 30,708 MPs/PU-mask) being the most prominent compared to autoclaving (219 MPs/PP-mask, 553 MPs/PU-mask) and alcohol spray (162 MPs/PP-mask, 18,333 MPs/PU-mask). Photoaging led to massive generation of MPs (8.8 × 104-3.7 × 105 MPs/PP-layer, 1.0 × 105 MPs/PU-layer) and NPs (5.2 × 109-3.6 × 1013 NPs/PP-layer, 3.5 × 1012 NPs/PU-layer) from masks, presenting highly fabric structure-dependent aging modes as "fragmentation" for fine fiber-structure PP mask and "erosion" for 3D mesh-structure PU mask. The MNPs derived from PP/PU mask caused significant deformities of Zebrafish (Danio rerio) larvae. These findings underscore the potential adverse effects of masks on humans and aquatic organisms, advocating to enhance proper use and rational disposal for masks.

Carrier effects of face mask-derived microplastics on metal ions: Enhanced adsorption by photoaging combined with biofilms, exemplified with Pb(â ¡).

Face masks have emerged as a significant source of microplastics (MPs) under the influence of biotic and abiotic interactions. However, the combined effects of abiotic photoaging and biofilm-loading on mask-derived MPs as carriers of metal ions are not clear. We investigated the Pb(Ⅱ) adsorption onto polypropylene (PP) and polyurethane (PU) mask-derived MPs treated by photoaging, biofilm-loading, and both combinations, evaluating the composite risks. PU mask-derived MPs (1.157.47 mg/g) exhibited greater Pb(Ⅱ) adsorption capacity than PP mask-derived MPs (0.842.08 mg/g) because of the presence of intrinsic carbonyl functional groups. Photoaging (30.5%, 88.4%), biofilm-loading (110.7%, 87.1%), and both combinations (146.7%, 547.0%) of PP and PU masks enhanced Pb(Ⅱ) adsorption compared to virgin mask-derived MPs due to the increase of oxygen-containing functional groups. High-throughput sequencing indicated that the structural morphology and chemical composition of masks significantly affected the microbial community. Adsorption mechanisms involved electrostatic force and surface complexation. A combination of photoaging and biofilms increased the ecological risk index of mask-derived MPs in freshwater, showing the risk level to be high (PP mask) and very high (PU mask). This research highlights the crucial role of photoaging combined with biofilms in controlling metal ion adsorption onto mask-derived MPs, thereby increasing the composite risks.

Optimization of an Ultrasound-Assisted Extraction Technique and the Effectiveness of the Sunscreen Components Isolated from Bletilla striata.

Bletilla striata is the dried tuber of B. striata (Thund.) Reichb.f., which has antibacterial, anti-inflammatory, anti-tumor, antioxidant and wound healing effects. Traditionally, it has been used for hemostasis therapy, as well as to treat sores, swelling and chapped skin. In this study, we used the ultraviolet (UV) absorbance rate of B. striata extracts as the index, and the extraction was varied with respect to the solid-liquid ratio, ethanol concentration, ultrasonic time and temperature in order to optimize the extraction process for its sunscreen components. The main compounds in the sunscreen ingredients of Baiji (B. striata) were analyzed using ultra-high-performance liquid chromatography combined with quadrupole time-of-flight tandem mass spectrometry. The sunscreen properties were subsequently evaluated in vitro using the 3M tape method. The results show that the optimal extraction conditions for the sunscreen components of B. striata were a solid-liquid ratio of 1:40 (g/mL), an ethanol concentration of 50%, an ultrasonic time of 50 min and a temperature of 60 °C. A power of 100 W and an ultrasonic frequency of 40 Hz were used throughout the experiments. Under these optimized conditions, the UV absorption rate of the isolated sunscreen components in the UVB region reached 84.38%, and the RSD was 0.11%. Eighteen compounds were identified, including eleven 2-isobutyl malic acid glucose oxybenzyl esters, four phenanthrenes, two bibenzyl and one α-isobutylmalic acid. An evaluation of the sunscreen properties showed that the average UVB absorption values for the sunscreen samples from different batches of B. striata ranged from 0.727 to 1.201. The sunscreen ingredients of the extracts from B. striata had a good UV absorption capacity in the UVB area, and they were effective in their sunscreen effects under medium-intensity sunlight. Therefore, this study will be an experimental reference for the extraction of sunscreen ingredients from the B. striata plant, and it provides evidence for the future development of B. striata as a candidate cosmetic raw material with UVB protection properties.

Identification of benzo[b]thiophene-1,1-dioxide derivatives as novel PHGDH covalent inhibitors.

The increased de novo serine biosynthesis confers many advantages for tumorigenesis and metastasis. Phosphoglycerate dehydrogenase (PHGDH), a rate-limiting enzyme in serine biogenesis, exhibits hyperactivity across multiple tumors and emerges as a promising target for cancer treatment. Through screening our in-house compound library, we identified compound Stattic as a potent PHGDH inhibitor (IC50 = 1.98 ± 0.66 µM). Subsequent exploration in structural activity relationships led to the discovery of compound B12 that demonstrated the increased enzymatic inhibitory activity (IC50 = 0.29 ± 0.02 µM). Furthermore, B12 exhibited robust inhibitory effects on the proliferation of MDA-MB-468, NCI-H1975, HT1080 and PC9 cells that overexpress PHGDH. Additionally, using a [U-13C6]-glucose tracing assay, B12 was found to reduce the production of glucose-derived serine in MDA-MB-468 cells. Finally, mass spectrometry-based peptide profiling, mutagenesis experiment and molecular docking study collectively suggested that B12 formed a covalent bond with Cys421 of PHGDH.

LncRNA-SERB promotes vasculogenic mimicry (VM) formation and tumor metastasis in renal cell carcinoma.

A growing body of evidence shows that vasculogenic mimicry (VM) is closely related to the invasion and metastasis of many tumor cells. Although the estrogen receptor (ER) can promote initiation and progression of renal cell carcinoma (RCC), how the downstream biomolecules are involved, and the detailed mechanisms of how ER expression is elevated in RCC remain to be further elucidated. Here, we discovered that long noncoding RNA (LncRNA)-SERB is highly expressed in tumor cells of RCC patients. We used multiple RCC cells and an in vivo mouse model for our study, and results indicated that LncRNA-SERB could boost RCC VM formation and cell invasion in vitro and in vivo. Although a previous report showed that ERß can affect the VM formation in RCC, it is unclear which factor could upregulate ERß. This is the first study to show LncRNA-SERB can be the upstream regulator of ERß to control RCC progression. Mechanistically, LncRNA-SERB may increase ERß via binding to the promoter area, and ERß functions through transcriptional regulation of zinc finger E-box binding homeobox 1 (ZEB1) to regulate VM formation. These results suggest that LncRNA-SERB promotes RCC cell VM formation and invasion by upregulating the ERß/ZEB1 axis and that therapeutic targeting of this newly identified pathway may better inhibit RCC progression.

A Retrospective Cohort Study of vNOTES Extraperitoneal Versus Laparoscopic Sacral Hysteropexy With Uterine Preserving Regarding Surgical Outcomes and Two-Year Follow-Up Results.

STUDY OBJECTIVE: To explore the effectiveness of transvaginal natural orifice transluminal endoscopic surgery extraperitoneal sacral hysteropexy (vNOTES-ESH) in women with symptomatic uterine prolapse over a 2 year follow-up. DESIGN: Retrospective cohort study. SETTING: Gynecological minimally invasive center. PATIENTS: Women undergoing sacral hysteropexy either by vNOTES (n = 25) or laparoscopic (n = 74) between November 2016 and December 2020. INTERVENTIONS: Both vNOTES-ESH and laparoscopic sacral hysteropexy (LAP-SH) were used for uterine prolapse. Demographic data, operative characteristics, perioperative outcomes, and follow-up information 2 years postsurgery in the 2 groups were retrospectively evaluated. RESULTS: Both procedures showed similar operation time, estimated blood loss, hospital stays, and pain scores (p >0.05). During a median follow-up of 59 (24-72) months, the surgical success rate was 96% for vNOTES-ESH and 97.3% for LAP-SH (p >0.05), with no differences in anatomical position or pelvic organ function after the operation. Women in the LAP-SH group experienced more bothersome symptoms of constipation compared to those in the vNOTES-ESH group (5.41% vs 0, p <0.05). Lastly, 1 case in the vNOTES-ESH group had a mesh exposed area of less than 1 cm2, and 1 patient in the LAP-SH group experienced stress incontinence. CONCLUSIONS: In this retrospective study, vNOTES-ESH met our patients' preference for uterine preservation and was a successful and effective treatment for uterine prolapse, providing good functional improvement in our follow-up. This procedure should be considered as an option for patients with pelvic organ prolapse.

Oncogenic KRAS Induces Arginine Auxotrophy and Confers a Therapeutic Vulnerability to SLC7A1 Inhibition in Non-Small Cell Lung Cancer.

The urea cycle is frequently rewired in cancer cells to meet the metabolic demands of cancer. Elucidation of the underlying mechanism by which oncogenic signaling mediates urea cycle reprogramming could help identify targetable metabolic vulnerabilities. In this study, we discovered that oncogenic activation of KRAS in non-small cell lung cancer (NSCLC) silenced the expression of argininosuccinate synthase 1 (ASS1), a urea cycle enzyme that catalyzes the production of arginine from aspartate and citrulline, and thereby diverted the utilization of aspartate to pyrimidine synthesis to meet the high demand for DNA replication. Specifically, KRAS signaling facilitated a hypoacetylated state in the promoter region of the ASS1 gene in a histone deacetylase 3-dependent manner, which in turn impeded the recruitment of c-MYC for ASS1 transcription. ASS1 suppression in KRAS-mutant NSCLC cells impaired the biosynthesis of arginine and rendered a dependency on the arginine transmembrane transporter SLC7A1 to import extracellular arginine. Depletion of SLC7A1 in both patient-derived organoid and xenograft models inhibited KRAS-driven NSCLC growth. Together, these findings uncover the role of oncogenic KRAS in rewiring urea cycle metabolism and identify SLC7A1-mediated arginine uptake as a therapeutic vulnerability for treating KRAS-mutant NSCLC. SIGNIFICANCE: ASS1 deficiency is induced by mutant KRAS in NSCLC to facilitate DNA synthesis and creates a dependency on SLC7A1, revealing dietary arginine restriction and SLC7A1 inhibition as potential therapeutic strategies.

Nomogram for predicting difficult total laparoscopic hysterectomy: a multi-institutional, retrospective model development and validation study.

BACKGROUND: Total laparoscopic hysterectomy (TLH) is the most commonly performed gynaecological surgery. However, the difficulty of the operation varies depending on the patient and surgeon. Subsequently, patient's outcomes and surgical efficiency are affected. The authors aimed to develop and validate a preoperative nomogram to predict the operative difficulty in patients undergoing TLH. METHODS: This retrospective study included 663 patients with TLH from Southwest Hospital and 102 patients from 958th Hospital in Chongqing, China. A multivariate logistic regression analysis was used to identify the independent predictors of operative difficulty, and a nomogram was constructed. The performance of the nomogram was validated internally and externally. RESULTS: The uterine weight, history of pelvic surgery, presence of adenomyosis, surgeon's years of practice, and annual hysterectomy volume were identified as significant independent predictors of operative difficulty. The nomogram demonstrated good discrimination in the training dataset [area under the receiver operating characteristic curve (AUC), 0.827 (95% CI, 0.783-0.872], internal validation dataset [AUC, 0.793 (95% CI, 0.714-0.872)], and external validation dataset [AUC, 0.756 [95% CI, 0.658-0.854)]. The calibration curves showed good agreement between the predictions and observations for both internal and external validations. CONCLUSION: The developed nomogram accurately predicted the operative difficulty of TLH, facilitated preoperative planning and patient counselling, and optimized surgical training. Further prospective multicenter clinical studies are required to optimize and validate this model.

Bioinformatics identification of characteristic genes of cervical cancer via an artificial neural network.

BACKGROUND: Artificial neural networks (ANNs) have been extensively used in the field of medicine. The present hypothesis-free study sought to use an ANN to identify the characteristic genes of cervical cancer (CC). METHODS: RNA sequencing profiles were obtained from the GSE7410, GSE9750, GSE63514, and GSE52903 datasets. The differentially expressed genes (DEGs) were identified and compared between the normal and CC tissues. An ANN analysis was conducted to obtain the random-forest tree and to examine differences in gene filtering. A neural network model was established using the characteristic genes of CC, while the verification accuracy of the model was examined by Cox regression. The differences in the immune infiltrating cells between the normal cervical and CC tissues were compared by CIBERSORT (an analytical tool can provide an estimation of the abundances of member cell types in a mixed cell population). RESULTS: Nine genes' characteristics for CC were identified: cyclin-dependent kinase inhibitor 2A (CDKN2A), chromosome 1 open reading frame 112 (C1orf112), helicase, lymphoid-specific (HELLS), mini-chromosome maintenance protein 5 (MCM5), mini-chromosome maintenance protein 2 (MCM2), kinetochore associated 1 (KNTC1), cysteine-rich secretory protein 3 (CRISP3), phytanoyl-CoA 2-hydroxylase interacting protein (PHYHIP), and cornulin (CRNN). CONCLUSIONS: ANN is a robust neural network model that can be used to potentially predict CC based on the gene score. It can provide novel insights into the pathogenesis and molecular mechanisms of CC.

Low-Dose Chemotherapy Preferentially Shapes the Ileal Microbiome and Augments the Response to Immune Checkpoint Blockade by Activating AIM2 Inflammasome in Ileal Epithelial Cells.

Intervention of the gut microbiome is a promising adjuvant strategy in cancer immunotherapy. Chemotherapeutic agents are recognized for their substantial impacts on the gut microbiome, yet their therapeutic potential as microbiome modulators remains uncertain, due to the complexity of microbiome-host-drug interactions. Here, it is showed that low-dose chemotherapy preferentially shapes the ileal microbiome to augment the extraintestinal immune response to anti-programmed death-1 (anti-PD-1) therapy without causing intestinal toxicity. Mechanistically, low-dose chemotherapy causes DNA damage restricted to highly-proliferative ileal epithelial cells, resulting in the accumulation of cytosolic dsDNA and the activation of the absent in melanoma 2 (AIM2) inflammasome. AIM2-dependent IL-18 secretion triggers the interplay between proximal Th1 cells and Paneth cells in ileal crypts, impairing the local antimicrobial host defense and resulting in ileal microbiome change. Intestinal epithelium-specific knockout of AIM2 in mice significantly attenuates CPT-11-caused IL-18 secretion, Paneth cell dysfunction, and ileal microbiome alteration. Moreover, AIM2 deficiency in mice or antibiotic microbial depletion attenuates chemotherapy-augmented antitumor responses to anti-PD1 therapy. Collectively, these findings provide mechanistic insights into how chemotherapy-induced genomic stress is transduced to gut microbiome change and support the rationale of applying low-dose chemotherapy as a promising adjuvant strategy in cancer immunotherapy with minimal toxicity.

Customized fluorescent probe for peering into the expression of butyrylcholinesterase in thyroid cancer.

BACKGROUND: Thyroid cancer has been increasingly prevalent in recent years. The main diagnostic methods for thyroid are B-ultrasound scan, serum detection and puncture detection. However, these methods are invasive and complex. It is a pressing need to develop non-invasive or minimally invasive methods for thyroid cancer diagnosis. Fluorescence method as a non-invasive detection method has attracted much attention. Butyrylcholinesterase (BChE) is a common enzyme in the human body, and many diseases affect its reduction. We found that BChE is also a marker for thyroid cancer. Therefore, it is of certain clinical value to explore the expression of BChE in thyroid cancer cells through a customized fluorescent probe to provide valuable experimental data and clues for studying the expression of thyroid cancer marker to reflect thyroid status. RESULTS: In this study, we customized a fluorescent probe named Kang-BChE, which is easy to synthesize with a high yield. The experimental results show that the probe Kang-BChE can detect BChE in the linear range of 0-900 U L-1 (R2 = 0.9963), and the detection limit is as low as 3.93 U L-1 (λex/em = 550/689 nm). In addition, Kang-BChE probes have low cytotoxicity, good specificity, and can completely eliminate interference from acetylcholinesterase (AChE). Kang-BChE showed excellent stability in the detection of complex biological samples in serum recovery experiments (95.64-103.12 %). This study was the first time using Kang-BChE to study the low expression of BChE in thyroid cancer cells (Tpc-1 cells). In addition, we observed that H2O2 concentration in Tpc-1 cells was positively correlated with BChE activity. SIGNIFICANCE: Kang-BChE is expected to be an important tool for monitoring the change of BChE content in complex biological environments due to its excellent performance. Kang-BChE can also be used to explore the influence of molecules in more organisms on the change of BChE content due to its excellent anti-interference ability. We expect that Kang-BChE can play a significant role in the clinical diagnosis and treatment of thyroid cancer.

Tetrandrine synergizes with MAPK inhibitors in treating KRAS-mutant pancreatic ductal adenocarcinoma via collaboratively modulating the TRAIL-death receptor axis.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal malignancies lacking effective therapies. KRAS mutations that occur in over 90% of PDAC are major oncogenic drivers of PDAC. The MAPK signaling pathway plays a central role in KRAS-driven oncogenic signaling. However, pharmacological inhibitors of the MAPK pathway are poorly responded in KRAS-mutant PDAC, raising a compelling need to understand the mechanism behind and to seek new therapeutic solutions. Herein, we perform a screen utilizing a library composed of 800 naturally-derived bioactive compounds to identify natural products that are able to sensitize KRAS-mutant PDAC cells to the MAPK inhibition. We discover that tetrandrine, a natural bisbenzylisoquinoline alkaloid, shows a synergistic effect with MAPK inhibitors in PDAC cells and xenograft models. Mechanistically, pharmacological inhibition of the MAPK pathway exhibits a double-edged impact on the TRAIL-death receptor axis, transcriptionally upregulating TRAIL yet downregulating its agonistic receptors DR4 and DR5, which may explain the limited therapeutic outcomes of MAPK inhibitors in KRAS-mutant PDAC. Of great interest, tetrandrine stabilizes DR4/DR5 protein via impairing ubiquitination-mediated protein degradation, thereby allowing a synergy with MAPK inhibition in inducing apoptosis in KRAS-mutant PDAC. Our findings identify a new combinatorial approach for treating KRAS-mutant PDAC and highlight the role of TRAIL-DR4/DR5 axis in dictating the therapeutic outcome in KRAS-mutant PDAC.

A novel coagulation-related lncRNA predicts the prognosis and immune of clear cell renal cell carcinoma.

Renal cell cancer is associated with the coagulation system. Long non-coding RNA (lncRNA) expression is closely associated with the development of clear cell renal cell carcinoma (ccRCC). The aim of this study was to build a novel lncRNA model to predict the prognosis and immunological state of ccRCC. The transcriptomic data and clinical data of ccRCC were retrieved from TCGA database, subsequently, the lasso regression and lambda spectra were used to filter prognostic lncRNAs. ROC curves and the C-index were used to confirm the predictive effectiveness of this model. We also explored the difference in immune infiltration, immune checkpoints, tumor mutation burden (TMB) and drug sensitivity between the high- and low-risk groups. We created an 8 lncRNA model for predicting the outcome of ccRCC. Multivariate Cox regression analysis showed that age, tumor grade, and risk score are independent prognostic factors for ccRCC patients. ROC curve and C-index revealed the model had a good performance in predicting prognosis of ccRCC. GO and KEGG analysis showed that coagulation related genes were related to immune response. In addition, high risk group had greater TMB level and higher immune checkpoints expression. Sorafenib, Imatinib, Pazopanib, and etoposide had higher half maximal inhibitory concentration (IC50) in the high risk group whereas Sunitinib and Bosutinib had lower IC50. This novel coagulation-related long noncoding RNAs model could predict the prognosis of patients with ccRCC, and coagulation-related lncRNA may be connected to the tumor microenvironment and gene mutation of ccRCC.

[Retracted] KIF22 promotes bladder cancer progression by activating the expression of CDCA3.

Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that certain of the colony formation assay data shown in Fig. 3A on p. 7 and the immunohistochemistry data in Fig. 5D were strikingly similar to data that had already appeared in previous publications. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were under consideration for publication, prior to its submission to International Journal of Molecular Medicine, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they accepted the decision to retract this paper. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 48: 211, 2021; DOI: 10.3892/ijmm.2021.5044].

Tuning the surface functionality of polyethylene glycol-modified graphene oxide/chitosan composite for efficient removal of dye.

There has been a lot of attention on water pollution by dyes in recent years because of their serious toxicological implications on human health and the environment. Therefore, the current study presented a novel polyethylene glycol-functionalized graphene oxide/chitosan composite (PEG-GO/CS) to remove dyes from aqueous solutions. Several characterization techniques, such as SEM, TEM, FTIR, TGA/DTG, XRD, and XPS, were employed to correlate the structure-property relationship between the adsorption performance and PEG-GO/CS composites. Taguchi's (L25) approach was used to optimize the batch adsorption process variables [pH, contact time, adsorbent dose, and initial concentration of methyl orange (MO)] for maximal adsorption capacity. pH = 2, contact time = 90 min, adsorbent dose = 10 mg/10 mL, and MO initial concentration = 200 mg/L were found to be optimal. The material has a maximum adsorption capacity of 271 mg/g for MO at room temperature. With the greatest R2 = 0.8930 values, the Langmuir isotherm model was shown to be the most appropriate. Compared to the pseudo-first-order model (R2 = 0.9685), the pseudo-second-order model (R2 = 0.9707) better fits the kinetic data. Electrostatic interactions were the dominant mechanism underlying MO sorption onto the PEG/GO-CS composite. The as-synthesized composite was reusable for up to three adsorption cycles. Thus, the PEG/GO-CS composite fabricated through a simple procedure may remove MO and other similar organic dyes in real contaminated water.

Hedgehog pathway orchestrates the interplay of histone modifications and tailors combination epigenetic therapies in breast cancer.

Epigenetic therapies that cause genome-wide epigenetic alterations, could trigger local interplay between different histone marks, leading to a switch of transcriptional outcome and therapeutic responses of epigenetic treatment. However, in human cancers with diverse oncogenic activation, how oncogenic pathways cooperate with epigenetic modifiers to regulate the histone mark interplay is poorly understood. We herein discover that the hedgehog (Hh) pathway reprograms the histone methylation landscape in breast cancer, especially in triple-negative breast cancer (TNBC). This facilitates the histone acetylation caused by histone deacetylase (HDAC) inhibitors and gives rise to new therapeutic vulnerability of combination therapies. Specifically, overexpression of zinc finger protein of the cerebellum 1 (ZIC1) in breast cancer promotes Hh activation, facilitating the switch of H3K27 methylation (H3K27me) to acetylation (H3K27ac). The mutually exclusive relationship of H3K27me and H3K27ac allows their functional interplay at oncogenic gene locus and switches therapeutic outcomes. Using multiple in vivo breast cancer models including patient-derived TNBC xenograft, we show that Hh signaling-orchestrated H3K27me and H3K27ac interplay tailors combination epigenetic drugs in treating breast cancer. Together, this study reveals the new role of Hh signaling-regulated histone modifications interplay in responding to HDAC inhibitors and suggests new epigenetically-targeted therapeutic solutions for treating TNBC.

The efficacy of ureteroscopic triage in increasing the cure rate of the first-line treatment for a ureterovaginal fistula resulting from radical hysterectomy.

Study objective: To explore the effect of pretreatment with ureteroscopic triage for iatrogenic ureterovaginal fistula (UVF) resulting from radical hysterectomy. Design: A retrospective cohort study. Setting: Department of gynecology at a tertiary medical center. Patients: Women diagnosed with UVF secondary to radical hysterectomy at our center between April 2008 to June 2018. Interventions: The patients were divided into two groups according to whether pretreatment with ureteroscopic triage was performed. Those in the non-triage group underwent retrograde placement of a double-J stent immediately following diagnosis as the first-line therapy. Patients in the triage group were first evaluated under ureteroscopy, their ureteral injuries were then classified into different grades and then underwent different treatments as the first-line therapy, including stent placement or reconstruction surgeries. The cure rate of the first-line therapy and the timeliness of the implementation of adjuvant radiotherapy were subsequently analyzed. Measurements and main results: Ninety-eight UVF patients were included. The demographics, ECOG status, stage of cervical cancer (FIGO 2009), types and onset time of symptoms were not different between the two groups. There were 54 patients in the nontriage group, with an overall first-line cure rate of 70.4% and a timely implementation rate of adjuvant radiotherapy of 38.5%. There were 44 patients in the evaluation group, with an overall first-line cure rate of 93.2% and a timely implementation rate of adjuvant radiotherapy of 90.0%. The differences were statistically significant (p < 0.001). Conclusion: Ureteroscopic triage of ureteral injuries can guide the selection of the optimal first-line therapy for patients with UVF secondary to radical hysterectomy, increase the cure rate and ensure the timely implementation of adjuvant radiotherapy.