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Developing solution-processable and stable scintillators with high light yields, low detection limits and high imaging resolutions holds great significance for flexible X-ray imaging. However, attaining an optimal equilibrium among X-ray absorption capacity, exciton utilization efficiency, and decay lifetime of scintillators remains a substantial challenge. Here, a new Cu(I) halide complex was synthesized in a mild condition. It exhibits intense blue thermally activated delayed fluorescence (TADF), remarkable aggregation-induced emission (AIE) characteristic, as well as good water-oxygen stability and photochemical stability. Notably, the complex shows excellent radiation resistance and efficient radioluminescence (RL) with an ultra-low detection limit of 42.5 nGy air s -1 . This superior scintillation performance can be attributed to the synergistic effect of effective X-ray absorption by the heavy Cu 2 I 2 core, the high radiation-induced exciton utilization rate in TADF process, and the remarkable suppression of non-radiative transitions by the restriction of intramolecular motions in solid state. Furthermore, the favourable solution processability of the complex facilitates the successful fabrication of a flexible film, achieving high-quality X-ray imaging with a resolution of 17.3 lp mm -1 . This work highlights the potential of hybrid Cu(I) halides with AIE-TADF effects for high-energy radiation detection and imaging, opening up new avenues for the exploration of cost-effective and high-performance scintillators., (© 2025 Wiley-VCH GmbH.)

Sequence similarity 20 family member C (Fam20C), a Golgi casein kinase, has a gradually elucidated mechanism in triple-negative breast cancer (TNBC) and is considered a possible target for therapeutic intervention. In this study, we combined virtual screening and chemical synthesis methods to obtain a new small-molecule Fam20C inhibitor, compound 5k, which possesses desirable kinase inhibitory activity against Fam20C and significant anti-proliferative activity against MDA-MB-231 and BT-549 cells. Subsequently, cellular thermal shift assay (CETSA), molecular docking, and molecular dynamics (MD) simulations revealed that compound 5k binds to Fam20C. Moreover, compound 5k showed favorable antitumor efficacy in TNBC cells and xenograft models by promoting apoptosis and inhibiting migration. Mechanistically, compound 5k can inhibit the proliferation, promote apoptosis, and inhibit migration of TNBC cells by targeting Fam20C, thereby inhibiting the deterioration of TNBC and preventing its progression. Taken together, these results suggest that compound 5k can be utilized as a novel Fam20C inhibitor, laying a foundation for the discovery of more small-molecule drugs for the treatment of TNBC in the future., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The urological system, including kidneys, ureters, bladder, urethra and prostate is known to be vital for blood filtration, waste elimination and electrolyte balance. Notably, urological system cancers represent a significant portion of global cancer diagnoses and mortalities. The current therapeutic strategies for early-stage cancer primarily involve resection surgery, which significantly affects the quality of life of patients, whereas advanced-stage cancer often relies on less effective chemo- or radiotherapy. Recently, accumulating evidence has revealed that autophagy, a crucial process in which excess organelles or inclusions within cells are removed to maintain cell homeostasis, has numerous links to urological system cancers. In this review, we focus on summarizing the underlying two-sided mechanisms of autophagy in urological system cancers. We also review the current clinical drugs targeting autophagy, which demonstrate significant potential in improving treatment outcomes for urological system cancers. In addition, we provide an overview of the research status of novel small molecule compounds targeting autophagy that are in the preclinical stages of investigation. Furthermore, drug combinations based on autophagy modulation strategies in urological system cancers are systematically summarized and discussed. These findings provide comprehensive new insight for the future discovery of more autophagy-related drug candidates., Competing Interests: Declaration of competing interest The authors have declared that no competing interest exists., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Advancements in radiotherapy (RT) technology have led to the prominence of precision RT in head and neck cancer (HNC) treatment. The new progress in precision RT offers more efficient therapy, potentially improving outcomes for HNC patients., Objective: The present cross-sectional study aimed to assess the knowledge, attitude, and practice (KAP) of patients in advanced precision RT for HNC treatment., Methods: This study enrolled HNC patients at the Affiliated Hospital of Hebei University of Engineering between October 2023 and May 2024. Then, the demographic data and KAP scores were collected using an investigator-designed questionnaire. Afterwards, descriptive statistics were provided for all study variables, and the relationship among KAP was analyzed using appropriate statistical tests, including Spearman correlation, logistic regression, and path analysis., Results: A total of 436 participants with a mean age of 52.03 ± 12.19 years old were included. The mean knowledge score, attitude score, and practice score were 18.33 ± 4.21, 36.14 ± 1.71, and 26.26 ± 1.83, respectively. Although most of the participants were unfamiliar with advanced precision RT, they expressed a high willingness to follow their doctor's recommendation for this treatment. The multivariable analysis revealed a positive association between attitude score and proactive practice. The path analysis revealed that knowledge directly influenced attitude and practice, while attitude directly impacted practice., Conclusion: HNC participants had poor knowledge of advanced precision RT techniques, but had a positive attitude and the willingness to undergo treatment when recommended by their physicians. These results suggest that improving patients' awareness for advanced precision RT can help to promote better attitude and advanced precision RT practice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Guo, Cai, Liu, Zhao, Xie, Li, Liu, Wang, Chen and Zhang.)

The activating transcription factor (ATF)/ cAMP-response element binding protein (CREB) family represents a large group of basic zone leucine zip (bZIP) transcription factors (TFs) with a variety of physiological functions, such as endoplasmic reticulum (ER) stress, amino acid stress, heat stress, oxidative stress, integrated stress response (ISR) and thus inducing cell survival or apoptosis. Interestingly, ATF family has been increasingly implicated in autophagy and ferroptosis in recent years. Thus, the ATF family is important for homeostasis and its dysregulation may promote disease progression including cancer. Current therapeutic approaches to modulate the ATF family include direct modulators, upstream modulators, post-translational modifications (PTMs) modulators. This review summarizes the structural domain and the PTMs feature of the ATF/CREB family and comprehensively explores the molecular regulatory mechanisms. On this basis, their pathways affecting proliferation, metastasis, and drug resistance in various types of cancer cells are sorted out and discussed. We then systematically summarize the status of the therapeutic applications of existing ATF family modulators and finally look forward to the future prospect of clinical applications in the treatment of tumors by modulating the ATF family., Competing Interests: Declaration of Competing Interest The authors have declared that no competing interest exists., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Retinol binding protein 4 (RBP4) is a mediator of inflammation and related to skin lesion formation, which suggests its engagement in psoriasis pathology and progression. This study intended to explore the change in RBP4 after systemic treatments, and its ability to predict treatment response in psoriasis patients., Methods: This prospective study enrolled 85 psoriasis patients and 20 healthy subjects. Plasma RBP4 was detected by enzyme-linked immunosorbent assay at baseline and 12th week (W12) after systemic treatments in psoriasis patients, as well as after enrollment in healthy subjects. Psoriasis Area and Severity Index (PASI) 75 and PASI 90 were evaluated at W12 in psoriasis patients., Results: RBP4 at baseline was higher in psoriasis patients than in healthy subjects [median (interquartile range): 13.39 (9.71-22.92) versus 9.59 (6.57-13.72) µg/mL] (P = 0.003). In psoriasis patients, 50 (58.8%) patients achieved PASI 75 at W12, and 25 (29.4%) patients achieved PASI 90 at W12. RBP4 was decreased at W12 compared to its level at baseline (P < 0.001). Lower RBP4 at baseline predicted achieving PASI 75 at W12 (P = 0.038). Greater RBP4 change (baseline-W12) precited achieving PASI 75 (P = 0.036) and PASI 90 (P = 0.045) at W12. Receiver operating characteristic curves suggested that after adjustment for all clinical features, RBP4 at baseline and RBP4 change (baseline-W12) had an acceptable ability to predict PASI 75 and PASI 90 at W12 with all area under curve values > 0.7., Conclusion: Plasma RBP4 is decreased after systemic treatments, and its low baseline level and greater decline after treatments predict good treatment response in psoriasis patients., (© 2024. The Author(s).)

Background: Oral squamous cell carcinoma (OSCC) is originating from oral mucosal epithelial cells. Autophagy plays a crucial role in cancer treatment by promoting cellular self-degradation and eliminating damaged components, thereby enhancing therapeutic efficacy. In this study, we aim to identify a novel autophagy-related biomarker to improve OSCC therapy., Methods: We firstly utilized Cox and Lasso analyses to identify that ATF6 is associated with OSCC prognosis, and validated the results by Kaplan-Meier survival analysis. We further identified the downstream pathways and related genes by enrichment analysis and WGCNA analysis. Subsequently, we used short interfering RNA to investigate the effects of ATF6 knockdown on proliferation, migration, apoptosis, and autophagy in SCC-9 and SCC-15 cells through cell viability assay, transwell assay, EdU incorporation assay, flow cytometry analysis, western blot analysis and immunofluorescence analysis, etc. RESULTS: Bioinformatics analyses showed that ATF6 overexpression was associated with prognosis and detrimental to survival. In vitro studies verified that ATF6 knockdown reduced OSCC cell proliferation and migration. Mechanistically, ATF6 knockdown could promote cellular autophagy and apoptosis., Conclusion: We propose that ATF6 holds potential as a prognostic biomarker linked to autophagy in OSCC. This study provides valuable clues for further exploration of targeted therapy against OSCC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Oral squamous cell carcinoma (OSCC), a malignancy originating from mucosal epithelial cells. Currently, triggering apoptotic cell death with anticancer drugs is the main way to inhibit OSCC cells. However, the capability to trigger apoptosis in tumors is constrained by the intrinsic resistance of tumor cells to apoptosis, hampering its effectiveness. Thus, utilizing alternative modes of non-apoptotic cell death offers new therapeutic possibilities, such as using a drug combination strategy to simultaneously induce ferroptosis and autophagy has the potential to improve OSCC therapy. In this study, we found the ferroptosis inducer RSL3 has certain inhibitory effects on the proliferation and migration of OSCC cells. Interestingly, our studies showed that RSL3 is also associated with autophagy activation. Based on this finding, we tried to combine RSL3 with the autophagy inducer LYN-1604 to improve the therapeutic effect. The results demonstrated that simultaneous regulation of autophagy and ferroptosis significantly reduced the proliferation and migration of OSCC cells. Taken together, we demonstrated the therapeutic potential of RSL3 in OSCC cells and proposed that simultaneous activation of autophagy and ferroptosis have synergistic effects, which would provide valuable clues for further exploration of targeted therapy for OSCC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Metformin is currently a strong candidate antitumor agent for multiple cancers, and has the potential to inhibit cancer cell viability, growth, and proliferation. Metabolic reprogramming is a critical feature of cancer cells. However, the effects of metformin which targets glucose metabolism on HepG2 cancer cells remain unclear. In this study, to explore the effects of metformin on glucose metabolism in HepG2 cells, we conducted real-time metabolomic monitoring of live HepG2 cells treated with metformin using 13 C in-cell NMR spectroscopy. Metabolic tracing with U- 13 C 6 -glucose revealed that metformin significantly increased the production of 13 C-G3P and 13 C-glycerol, which were reported to attenuate liver cancer development, but decreased the production of potential oncogenesis-supportive metabolites, including 13 C-lactate, 13 C-alanine, 13 C-glycine, and 13 C-glutamate. Moreover, the expression levels of enzymes associated with the measured metabolites were carried out. The results showed that the levels of ALT1, MCT4, GPD2 and MPC1 were greatly reduced, which were consistent with the changes of measured metabolites in 13 C in-cell NMR spectroscopy. Overall, our approach directly provides fundamental insights into the effects of metformin on glucose metabolism in live HepG2 cells, and highlights the potential mechanism of metformin, including the increase in production of G3P and glycerol derived from glucose, as well as the inhibition of glucose incorporation into lactate, alanine, glutamate, and glycine., Competing Interests: Declaration of competing interest The authors state no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

H 2 O 2 is a widely used eco-friendly oxidant and a potential energy carrier. Photocatalytic H 2 O 2 production from water and O 2 is an ideal approach with the potential to address the current energy crisis and environmental issues. Three zig-zag two-dimensional coordination polymers (2D CPs), named CuX-dptz, were synthesized by a rapid and facile method at room temperature, showing preeminent H 2 O 2 photoproduction performance under pure water and open air without any additives. CuBr-dptz exhibits a H 2 O 2 production rate high up to 1874 μmol g -1  h -1 , exceeding most reported photocatalysts under this condition, even comparable to those supported by sacrificial agents and O 2 . The coordination environment of Cu can be modulated by halogen atoms (X=Cl, Br, I), which in turn affects the electron transfer process and finally determines the reaction activity. This is the first time that 2D CPs have been used for photocatalytic H 2 O 2 production in such challenging conditions, which provides a new pathway for the development of portable in situ H 2 O 2 photosynthesis devices., (© 2023 Wiley-VCH GmbH.)

Introduction: This study aimed to explore the expression profiles of fatty acid metabolism- related genes (FAMRGs) in patients with bladder cancer (BLCA)., Methods: The corresponding clinicopathological features of BLCA patients and RNA sequencing data were downloaded from TCGA and GSE13507. Univariate Cox regression was used to determine the prognostic value of FRGS in BLCA patients. LASSO regression analysis was then performed to select potential risk genes and eliminate genes that might overfit the model. Based on the independent prognostication-related FRGs, the nomogram survival model was established using the root mean square value of the R packet to predict the 1-year, 3-year, and 5-year survival rates of BLCA patients. By determining the area under the curve (AUC) value, the time-dependent receiver operating characteristic curve (ROC) was used to evaluate the prognostic efficiency of our model., Results: A total of 243 DEFRGs were identified. Twenty FRGs were found to be related to the prognosis of BLCA in the TCGA database. Survival curves showed that high-risk patients had significantly shorter OS than low-risk cases (p < 0.001). The AUC of risk was 0.784, which was superior to age, sex, and stage, suggesting that the risk score was more favorable in predicting OS than traditional pathologic prognostic factors. The AUC was 0.757 at 1 year, 0.732 at 3 years, and 0.733 at 5 year-OS., Conclusion: In this study, we demonstrated that a FAMRG prognosis biomarker is associated with the tumor immune microenvironment in patients with BLCA., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Near-infrared (NIR) fluorescence imaging-guided photodynamic therapy (PDT) technology plays an important role in treating various diseases and still attracts increasing research interests for developing novel photosensitizers (PSs) with outstanding performances. Conventional PSs such as porphyrin and rhodamine derivatives have easy self-aggregation properties in the physiological environment due to their inherent hydrophobic nature caused by their rigid molecular structure that induces strong intermolecular stacking π-π interaction, leading to serious fluorescence quenching and cytotoxic reactive oxygen species (ROS) reduction. Meanwhile, hypoxia is an inherent barrier in the microenvironment of solid tumors, seriously restricting the therapeutic outcome of conventional PDT. Aforementioned disadvantages should be overcome urgently to enhance the therapeutic effect of PSs. Novel NIR fluorescence-guided type I PSs with aggregation-induced emission (AIE), which features the advantages of improving fluorescent intensity and ROS generation efficiency at aggregation as well as outstanding oxygen tolerance, bring hope for resolving aforementioned problems simultaneously. At present, plenty of research works fully demonstrates the advancement of AIE-active PDT based on type I PSs. In this review, cutting-edge advances focusing on AIE-active NIR type I PSs that include the aspects of the photochemical mechanism of type I ROS generation, various molecular structures of reported type I PSs with NIR fluorescence and their design strategies, and typical anticancer applications are summarized. Finally, a brief conclusion is obtained, and the underlying challenges and prospects of AIE-active type I PSs are proposed., (© 2023 John Wiley & Sons Ltd.)

Alzheimer's disease (AD) is a serious neurodegenerative disease characterized by memory impairment, mental retardation, impaired motor balance, loss of self-care and even death. Among the complex and diverse pathological changes in AD, protein kinases are deeply involved in abnormal phosphorylation of Tau proteins to form intracellular neuronal fiber tangles, neuronal loss, extracellular β-amyloid (Aβ) deposits to form amyloid plaques, and synaptic disturbances. As a disease of the elderly, the growing geriatric population is directly driving the market demand for AD therapeutics, and protein kinases are potential targets for the future fight against AD. This perspective provides an in-depth look at the role of the major protein kinases (GSK-3β, CDK5, p38 MAPK, ERK1/2, and JNK3) in the pathogenesis of AD. At the same time, the development of different protein kinase inhibitors and the current state of clinical advancement are also outlined., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Aberrant expression or dysfunction of cyclin-dependent kinase 7(CDK7) and histone deacetylase 1 (HDAC1) are associated with the occurrence and progression of various cancers. In this study, we developed a series of dual-target inhibitors by designing and synthesizing compounds that incorporate the pharmacophores of THZ2 and SAHA. The most potent dual-target inhibitor displayed robust inhibitory activity against several types of cancer cells and demonstrated promising inhibitory effects on both CDK7 and HDAC1. After further mechanistic studies, it was discovered that this inhibitor effectively arrested HCT-116 cells at the G2 phase and induced apoptosis. Additionally, it also significantly hindered the migration of HCT-116 cells and exhibited notable anti-tumor effects. These findings offer strong support for the development of dual-target inhibitors of CDK7 and HDAC1 and provide a promising avenue for future cancer therapy., (© 2023 Wiley-VCH GmbH.)

Triple negative breast cancer (TNBC) is one of the most aggressive breast tumors, with a high rate of recurrence and metastasis as well as a poor prognosis. Consequently, it is urgent to find new targeted therapeutic strategies and development of corresponding drugs. Previous studies have shown that CDK12 inhibitors in combination with PARP1 inhibitors is able to induce synthetic lethality in TNBC cells. Here, we reported simultaneously inhibition of CDK12 and PARP1 by genetic or pharmacological approaches synergistically inhibited the proliferation of TNBC cells. Then, a series of small molecule inhibitors targeting both CDK12 and PARP1 were designed and synthesized. The new dual-target inhibitor (12e) showed potent inhibitory activity against CDK12 (IC 50  = 285 nM) and PARP1 (IC 50  = 34 nM), as well as good anti-proliferative effects in TNBC cell lines. Meanwhile, compound 12e showed favorable synergistic anti-tumor efficacy in cells and xenografts by inhibiting DNA damage repair, promoting cell cycle arrest and apoptosis. Taken together, we successfully synthesized the first effective CDK12-PARP1 dual inhibitor, which is expected to be an attractive therapeutic strategy for TNBC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

A meta-analysis investigation was executed to measure the wound healing rates (WHRs) and wound problems (WPs) of conventional circumcision (CC) compared with ring circumcision (RC). A comprehensive literature investigation till March 2023 was applied and 2347 interrelated investigations were reviewed. The 16 chosen investigations enclosed 25 838 individuals, with circumcision, were in the chosen investigations' starting point, 3252 of them were RC, and 2586 were CC. Odds ratio (OR) in addition to 95% confidence intervals (CIs) were used to compute the value of the WHRs and WPs of CC compared with RC by the dichotomous or continuous approaches and a fixed or random model. RC had a significantly lower wound infection rate (WIR) (OR, 0.58; 95% CI, 0.37-0.91, P = .002) and wound bleeding rate (WBR) (OR, 0.22; 95% CI, 0.12-0.42, P < .001) compared with those with CC. However, RC and CC had no significant difference in WHR (OR, 2.18; 95% CI, -0.73 to 5.09, P = .14), wound edema rate (WER) (OR, 1.11; 95% CI, 0.92-1.33, P = .28), and wound dehiscence rate (WDR) (OR, 0.98; 95% CI, 0.60-1.58, P = .93). RC had significantly lower WIR, and WBR, however, no significant difference in WHR, WER, and WDR compared with those with CC. However, care must be exercised when dealing with its values because of the low sample size of some of the nominated investigations for the meta-analysis., (© 2023 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

The transcription factor EB (TFEB) is a transcription factor of the MiT/TFE family that translocations from the cytoplasm to the nucleus in response to various stimuli, including lysosomal stress and nutrient starvation. By activating genes involved in lysosomal function, autophagy, and lipid metabolism, TFEB plays a crucial role in maintaining cellular homeostasis. Dysregulation of TFEB has been implicated in various diseases, including cancer, neurodegenerative diseases, metabolic diseases, cardiovascular diseases, infectious diseases, and inflammatory diseases. Therefore, modulating TFEB activity with agonists or inhibitors may have therapeutic potential. In this review, we reviewed the recently discovered regulatory mechanisms of TFEB and their impact on human diseases. Additionally, we also summarize the existing TFEB inhibitors and agonists (targeted and non-targeted) and discuss unresolved issues and future research directions in the field. In summary, this review sheds light on the crucial role of TFEB, which may pave the way for its translation from basic research to practical applications, bringing us closer to realizing the full potential of TFEB in various fields., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Dual leucine zipper kinase (DLK, MAP3K12), a serine/threonine protein kinase, plays a key role in neuronal development, as it regulates axon regeneration and degeneration through its downstream kinase. Importantly, DLK is closely related to the pathogenesis of numerous neurodegenerative diseases and the induction of β-cell apoptosis that leads to diabetes. In this review, we summarize the current understanding of DLK function, and then discuss the role of DLK signaling in human diseases. Furthermore, various types of small molecule inhibitors of DLK that have been published so far are described in detail in this paper, providing some strategies for the design of DLK small molecule inhibitors in the future., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Histone methylation is the most common histone modification and a highly dynamic regulator of gene transcription. Methylation of lysine residues can alter the structure of chromatin, helping to regulate DNA-based nuclear activities. Lysine demethylases control and maintain epigenetic factors that affect chromatin structure and cell characteristics. A variety of diseases, including malignant tumors, are connected to their dysregulation. Advances in biochemistry and pathogenesis have prompted the discovery of small molecule inhibitors and tool compounds that disrupt lysine demethylation. In this review, we focus on JmjC-domain-containing histone lysine demethylases (KDM2-7), discussing their structures and biological roles, representative inhibitors, and therapeutic potential in cancer therapy, and aiming to provide unique insights into the development of JmjC-KDM inhibitors., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Treponema pallidum (Tp) is a widespread and destructive pathogen that leads to syphilis. As the acknowledged executor of host immunity, macrophage plays vital roles in combating the invasion and migration of Tp. However, the mechanisms of these processes are largely unknown, especially the critical driver genes and associated modifications., Objective: We aimed to systematically dissect the global N6-methyladenosine (m 6 A) RNA modification patterns in Tp-infected macrophages., Methods: The RNA of Tp-infected/non-infected macrophage was extracted, followed by mRNA sequencing and methylated RNA immunoprecipitation (MeRIP) sequencing. Bioinformatics analysis was executed by m 6 A peaks and motifs identification, Gene ontology and signaling pathways analysis of differentially expressed genes, and comprehensive comparison. The m 6 A levels were measured by RNA Methylation Assay, and m 6 A modified genes were determined by qPCR., Results: Totally, 2623 unique and 3509 common m 6 A peaks were proved along with related transcripts in Tp-infected macrophages. The common m 6 A-related genes were enriched in the signals of oxidative stress, cell differentiation, and angiogenesis, while unique genes in those of metabolism, inflammation, and infection. And differentially expressed transcripts revealed various biological processes and pathways associated with catabolic and infection. They also experienced comprehensive analysis due to hyper-/hypo-methylation. And the m 6 A level of macrophage was elevated, along with qPCR validation of specific genes., Conclusion: With a particular m 6 A transcriptome-wide map, our study provides unprecedented insights into the RNA modification of macrophage stimulated by Tp in vitro, which partially differs from other infections and may provide clues to explore the immune process for syphilis., Competing Interests: Conflicts of interests The authors have no conflict of interest to declare., (Copyright © 2023 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.)

Chimeric antigen receptors (CARs) recognizing tumor-associated antigens (TAAs) effectively target tumor cells without using the major histocompatibility complex (MHC). However, CARs have inaccurate dose determination in clinical practice, and the methods that can solve this problem often produce cytotoxic substances, such as green fluorescent protein (GFP) insertion. Therefore, in this study, we tried to anchor harmless fluorescent labels on CAR-T cell membranes using highly biologically compatible strain-promoted alkyne-azide cycloaddition (SPAAC) without any byproducts. Our conjugated fluorescent label was stable on the CAR-T cell surface for at least two weeks, with excellent light stability and metrology. Also, this method enabled the rapid quantification of the living CAR-T cells without affecting their activity. Thus, this method is a promising reliable strategy for accurately diagnosing and treating cancer.

Cellular mitophagy means that cells selectively wrap and degrade damaged mitochondria through an autophagy mechanism, thus maintaining mitochondria and intracellular homeostasis. In recent years, mitophagy has received increasing attention as a research hotspot related to the pathogenesis of clinical diseases, such as neurodegenerative diseases, cardiovascular diseases, cancer, metabolic diseases, and so on. It has been found that the regulation of mitophagy may become a new direction for the treatment of some diseases. In addition, numerous small molecule modulators of mitophagy have also been reported, which provides new opportunities to comprehend the procedure and potential of therapeutic development. Taken together, in this review, we summarize current understanding of the mechanism of mitophagy, discuss the roles of mitophagy and its relationship with diseases, introduce the existing small-molecule pharmacological modulators of mitophagy and further highlight the significance of their development., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

CPS1, the rate-limiting enzyme that controls the first reaction of the urea cycle, is responsible for converting toxic ammonia into non-toxic urea in mammals. While disruption of the functions of CPS1 leads to elevated ammonia and nerve damage in the body, mainly manifested as urea cycle disorder. Moreover, accumulating evidence has recently revealed that CPS1 is involved in a variety of human diseases, including CPS1D, cardiovascular disease, cancers, and others. In particular, CPS1 expression varies among cancers, being overexpressed in some cancers and downregulated in others, suggesting that CPS1 may be a promising cancer therapeutic target. In addition, some small-molecule inhibitors of CPS1 have been reported, which have not been confirmed experimentally in malignancies, meaning their future role is far from certain. In this review, we describe the structure and function of CPS1, highlight its important roles in various human diseases, and further discuss the potential diagnostic and therapeutic implications of small molecule compounds targeting CPS1., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The response to neoadjuvant chemotherapy (NAC) is highly correlated with survival in breast cancer (BC) patients. The early prediction of the response to NAC could facilitate treatment adjustments on a patient-by-patient basis, which would improve patient outcomes and survival. Conventional techniques used for detecting circulating microRNAs (miRNAs), which act as biomarkers for the early prediction of NAC efficacy in BC patients, are associated with limitations such as low sensitivity and specificity. We designed a highly sensitive graphene oxide (GO)-based qRT-PCR method for detecting miRNAs associated with the chemotherapeutic response in BC patients. The results showed that miRNA levels at both the baseline and end of the first NAC cycle could help distinguish NAC responders from NAC nonresponders; BC patients with lower plasma miRNA levels were more likely to achieve pathological complete remission. Thus, GO-based qRT-PCR could facilitate early prediction of NAC efficacy in BC patients.

With the continuous development of Unmanned Aerial Vehicle (UAV) technology, UAVs are widely used in military and civilian fields. Multi-UAV networks are often referred to as flying ad hoc networks (FANET). Dividing multiple UAVs into clusters for management can reduce energy consumption, maximize network lifetime, and enhance network scalability to a certain extent, so UAV clustering is an important direction for UAV network applications. However, UAVs have the characteristics of limited energy resources and high mobility, which bring challenges to UAV cluster communication networking. Therefore, this paper proposes a clustering scheme for UAV clusters based on the binary whale optimization (BWOA) algorithm. First, the optimal number of clusters in the network is calculated based on the network bandwidth and node coverage constraints. Then, the cluster heads are selected based on the optimal number of clusters using the BWOA algorithm, and the clusters are divided based on the distance. Finally, the cluster maintenance strategy is set to achieve efficient maintenance of clusters. The experimental simulation results show that the scheme has better performance in terms of energy consumption and network lifetime compared with the BPSO and K-means-based schemes.

Multiple primary malignancies (MPMs) are defined as the coexistence of at least two unrelated primary malignancies in a single patient, with the tumors differing in their histology. MPMs in the same patient, when present within 6 months of the primary tumor diagnosis, are considered a synchronous occurrence. In this case report, we describe a 61-year-old man who presented with three distinct tumors concurrently in 2021: noninvasive urothelial carcinoma of the bladder, diffuse large B-cell lymphoma, and squamous cell carcinoma of the lung. We discuss the process of therapy and briefly review the literature. MPMs are increasing in incidence, requiring an interdisciplinary approach to diagnosis and treatment., Competing Interests: Conflict of interest: Authors state no conflict of interest., (© 2022 Risheng Huang et al., published by De Gruyter.)

Background: Human papillomavirus (HPV) infection and related diseases are difficult clinical challenges. The efficacy of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) in treating condyloma acuminata is remarkable, with high virus clearance and low recurrence rates. Podophyllotoxin (POD) is the first-line drug with a significant therapeutic effect on condyloma acuminata. However, no studies have determined whether POD-combined ALA-PDT improves high-risk (HR)-HPV-infected cell killing. We aimed to investigate whether POD-combined ALA-PDT could promote HPV-infected cell death more effectively than the single treatment and explore the underlying mechanism., Methods: In HeLa and SiHa cells, flow cytometry, EdU assay and LDH release test were used to detect apoptosis, cell proliferation change and necrosis, respectively. To investigate whether the combined therapy might activate apoptosis and induce endoplasmic reticulum (ER) stress, flow cytometry was used to determine intracellular levels of ROS and calcium, and Western blotting was used to determine the expression of related proteins. Mitochondrial membrane depolarization was detected by JC-1 assay. Immunofluorescence staining and Western blotting were used to detect the activation of autophagy., Results: Podophyllotoxin -combined ALA-PDT inhibited the proliferation and promoted apoptosis and necrosis more effectively than the single treatment at the same intensity and concentration. The activation of the caspase-dependent apoptosis pathway, ER stress and autophagy was more substantial in POD-combined ALA-PDT than with single treatments., Conclusion: Podophyllotoxin -combined ALA-PDT effectively promoted cell death through several pathways in HeLa and SiHa cells. This combination might be a promising therapeutic strategy for the HR-HPV infection., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The use of a high volume of industrial solid waste mineral admixture and hybrid fiber can greatly reduce the amount of cement in mortar or concrete, improve its performance, ensure the service properties of mortar or concrete, and reuse industrial solid waste to reduce the environmental burden, which has significant research significance. In this paper, the mechanical properties, wear resistance and microstructure of hybrid fiber-reinforced mortar (HFRM) with a high content of industrial solid waste mineral admixture were systematically studied under different water/binder ratios. Mineral admixtures include fly ash, silica fume and granulated blast furnace slag (slag). The total content of hybrid glass fiber (GF) and polypropylene fiber (PPF) was 2% by volume fractions, and six different water/binder ratios ranging from 0.27 to 0.62 were used. The following conclusions were drawn: fibers have a significant negative effect on the properties of mortars with a low water/binder ratio (w/b = 0.27) and high content of mineral admixtures. In general, the effect of adding hybrid fiber on improving the wear resistance of mortar is more obvious. The average residual weight of hybrid fiber-reinforced mortar is the highest after the wear resistance test. Comprehensively considering the compressive strength, flexural strength, wear resistance and microstructure of the mortar samples, G8PP2-0.40 is the optimal mix ratio. At this time, the replacement rates of fly ash, silica fume and slag are: 20%, 5% and 30%, the water/binder ratio is 0.40, and the content of GF and PPF is 1.6% and 0.4%, respectively.

Efficient resolution of oxidative stress, inflammation, and bacterial infections is crucial for wound healing. To surmount these problems, tannic acid (TA)-bridged CeO 2 microcubes and chitosan (CS) (CS-TA@CeO 2 ) cryogel was fabricated through hydrogen bonding interactions as a multifunctional wound dressing. Successful introduction and uniform incorporation TA@CeO 2 microtubules enter the CS network. Thus-obtained CS-TA@CeO 2 cryogels displayed a suitable porous structure and swelling rate. Cryogels has excellent tissue adhesion, blood cell coagulation and hemostasis, anti-infection, and cell recruitment functions. In addition, the cryogel also showed good antibacterial activity against gram-positive bacteria and gram-negative bacteria. Based on the in vivo study of the multifunctional mixed cryogels, it promotes fibroblasts' adhesion and proliferation and significantly improves cell proliferation and tissue remodelling in wound beds. Furthermore, the chronic wound healing process in infected full-thickness skin defect models showed that cryogels significantly enhanced angiogenesis, collagen deposition and granulation tissue formation by providing a large amount of antioxidant activity. Therefore, this multifunctional mixed cryogels has potential clinical application value., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The study analyzes the significance of miR-141 and extracellular matrix metalloproteinase-induced molecule (CD147) in bladder cancer cells and their correlation with tumor grade. A total of 87 bladder cancer patients for diagnosis and treatment from August 2020 to August 2021 are selected. All patients underwent pathological biopsy, and their cancer tissues and adjacent tissue cells are extracted. RT-PCR is used to complete the miR-141 relative expression level, and the immunohistochemical method is used to detect the expression of CD147 in patients. The miR-141 and CD147-positive rates are compared, and the relative expression levels of miR-141 and CD147-positive rates in cells of different tumor grades are compared. Spearman correlation coefficient is used to analyze the correlation of CD147 and bladder cancer. The prognosis of patients with different expression levels of miR-141 and CD147 is compared. Both miR-141 and CD147 are highly expressed in bladder cancer tissues, and their expression levels are significantly different from those of normal adjacent cells. In addition, the above two indicators are closely related to and related to the tumor grade of bladder cancer patients, and the high expression of miR-141 and CD147 brings the poor prognosis effect to bladder cancer patients., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2022 Chao Liu et al.)

Background: A keloid is a disease of excessive fibrosis that is characterized by the aberrant proliferation of fibroblasts. However, the molecular mechanisms of fibroblasts during the development of keloids remain unclear. This study aims to identify new molecular targets that promote the proliferation and migration of keloid fibroblasts, providing new ideas for the prevention and treatment of keloids., Methods: We utilized bioinformatics tools to analyze data from keloid fibroblasts (KFs) available in the Gene Expression Omnibus (GEO) database to identify the key genes involved in keloid development. Homeobox C6 ( HOXC6 ) emerged as a hub gene in KFs from the GEO database was verified in keloid tissue samples and KFs using reverse transcription-quantitative polymerase chain reaction, western blot (WB) and immunohistochemistry. Subsequently, the effects of downregulated HOXC6 expression on the cellular behaviors of KFs were examined by performing Cell Counting Kit-8, flow cytometry, transwell migration and WB assays. Meanwhile, we performed transcriptome sequencing and gene set enrichment analysis (GSEA) to further explore HOXC6-related mechanisms and validated the signaling pathways by performing a series of experiments., Results: HOXC6 was the top-ranking hub gene of KFs in microarray datasets from GEO and was upregulated in keloid tissue samples and KFs. Downregulation of HOXC6 inhibited proliferation, migration and extracellular matrix (ECM) accumulation and promoted KF apoptosis. GSEA predicted that the hypoxia signaling pathway was associated with HOXC6 in KFs. Transcriptome sequencing suggested that the extracellular regulated protein kinase (ERK) pathway was one of the downstream pathways of HOXC6 in KFs. Our experiments confirmed that hypoxia-inducible factor-1α (HIF-1α) upregulates HOXC6 , contributing to KFs proliferation, migration, apoptosis inhibition and collagen accumulation through the ERK signaling pathway., Conclusions: Our findings first revealed that HOXC6 acts as an oncogenic driver in the molecular mechanisms of fibroblasts in keloids. The HIF-1α/HOXC6/ERK axis promotes proliferation, migration and ECM production by KFs, contributing to the progression of keloids. Taken together, HOXC6 may serve as a promising novel therapeutic target and new focus for research designed to understand the pathogenesis of keloids., (© The Author(s) 2022. Published by Oxford University Press.)

Materials exhibiting aggregation-induced emission (AIE) behaviour enable strong emission in solid state and can respond to various external stimuli, which may facilitate the development of materials for optical sensing, bioimaging or optoelectronic devices. Herein, we use an AIE luminogen 2',5'-diphenyl-[1,1':4',1"-terphenyl]-4,4"-dicarboxylic acid as the ligand to prepare an AIEgen-based MOF (metal-organic framework) named FJI-H31. FJI-H31 exhibits bright luminescence under ambient conditions (under air and at room temperature), but almost no emission is observed under vacuum. Our investigation shows that the emission intensity displays a smooth and reversible enhancement with increased gas pressure, which may be attributed to the restriction of intramolecular motion brought by structural deformation under pressure stimulus. Unlike most pressure-responsive MOFs, the luminescence reverts to its original state once gas pressure recovers. By virtue of its unique optical properties, a luminescent MOF with sensing ability of gas-pressure is realized., (© 2022. The Author(s).)

Background: Previous studies have confirmed that the bacterium Treponema pallidum (TP) or its proteins provide signals to macrophages that induce an inflammatory response; however, little is known about the negative regulation of this macrophage-mediated inflammatory response during syphilis infection or the underlying mechanism. Recent evidence suggests the role of the RNA modification, N 6 -adenosine methylation (m6A), in regulating the inflammatory response and pathogen-host cell interactions. Therefore, we hypothesized that m6A plays a role in the regulation of the inflammatory response in macrophages exposed to TP., Methods: We first assessed m6A levels in TP-infected macrophages differentiated from the human monocyte cell line THP-1. The binding and interaction between the m6A "writer" methyltransferase-like 3 (METTL3) or the m6A "reader" YT521-B homology (YTH) domain-containing protein YTHDF1 and the suppressor of cytokine signaling 3 (SOCS3), as a major regulator of the inflammatory response, were explored in differentiated TP-infected THP-1 cells as well as in secondary syphilitic lesions from patients. The mechanisms by which YTHDF1 and SOCS3 regulate the inflammatory response in macrophages were assessed., Results and Conclusion: After macrophages were stimulated by TP, YTHDF1 was upregulated in the cells. YTHDF1 was also upregulated in the syphilitic lesions compared to adjacent tissue in patients. YTHDF1 recognizes and binds to the m6A methylation site of SOCS3 mRNA, consequently promoting its translation, thereby inhibiting the JAK2/STAT3 pathway, and reducing the secretion of inflammatory factors, which results in anti-inflammatory regulation. This study provides the first demonstration of the role of m6A methylation in the pathological process of syphilis and further offers new insight into the pathogenesis of TP infection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Teng, Jiang, Zhang, Luo, Liao and Yang.)

Background: High-risk human papillomavirus infection is closely related to the development of several diseases, including cervical cancer and condyloma acuminatum. We recently designed a new photosensitizer, 1-triphenylaminebenzo[c][1,2,5]thiadiazole-4-yl)styryl)-1-methylpyridin-1-ium iodide salt (TBZPy), which shows good photodynamic properties. In this study, we explored the mechanism of action of the TBZPy photosensitizer and its potential application in the treatment of high-risk human papillomavirus-related diseases., Methods: HeLa cells (infected by the high-risk human papillomavirus strain HPV18) were treated with TBZPy-photodynamic therapy (PDT). Cell viability, production of reactive oxygen species, apoptosis, and mitochondrial membrane depolarization were evaluated using cell counting kit-8, immunofluorescence, and flow cytometry assays, respectively. Expression levels of the anti-apoptotic proteins Bcl-2 and Bcl-X L ; pro-apoptotic proteins Bax, cytochrome C, cleaved caspase 3, and cleaved caspase 9; and the mitochondrial stress protein heat shock protein 60 were examined by western blotting., Results: TBZPy-PDT inhibited the viability and promoted reactive oxygen species production, lactate dehydrogenase release, and apoptosis of HeLa cells in vitro. TBZPy-PDT also promoted the loss of mitochondrial membrane potential, downregulated the expression of anti-apoptotic proteins, and upregulated the expression of pro-apoptotic proteins. Moreover, TBZPy-PDT downregulated the expression of the human papillomavirus E6 and E7 proteins., Conclusion: Our study demonstrates the effectiveness of TBZPy-PDT against human papillomavirus-related diseases. These findings provide a foundation for using this novel photosensitizer to treat diseases associated with high-risk human papillomavirus infection., (Copyright © 2021. Published by Elsevier B.V.)

Infectious diseases (such as Corona Virus Disease 2019) and tumors pose a tremendous challenge to global public health. Early diagnosis of infectious diseases and tumors can lead to effective control and early intervention of the patient's condition. Over the past few decades, carbon nanomaterials (CNs) have attracted widespread attention in different scientific disciplines. In the field of biomedicine, carbon nanotubes, graphene, carbon quantum dots and fullerenes have the ability of improving the accuracy of the diagnosis by the improvement of the diagnostic approaches. Therefore, this review highlights their applications in the diagnosis of infectious diseases and tumors over the past five years. Recent advances in the field of biosensing, bioimaging, and nucleic acid amplification by such CNs are introduced and discussed, emphasizing the importance of their unique properties in infectious disease and tumor diagnosis and the challenges and opportunities that exist for future clinical applications. Although the application of CNs in the diagnosis of several diseases is still at a beginning stage, biosensors, bioimaging technologies and nucleic acid amplification technologies built on CNs represent a new generation of promising diagnostic tools that further support their potential application in infectious disease and tumor diagnosis., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

In this study, we aim to investigate the clinical features and outcomes of multichanneled aortic dissection (MCAD) and double-channeled aortic dissection (DCAD) in acute type B aortic dissection (TBAD) patients who underwent thoracic endovascular aortic repair (TEVAR).In total, 479 consecutive acute TBAD patients treated with TEVAR from April 2002 to May 2020 were retrospectively enrolled in this study. The MCAD group was defined as those of multichanneled morphology by initial computed tomography angiography (CTA) (n = 61), whereas the DCAD group was defined as those with double-channeled morphology by initial CTA (n = 418). The clinical and morphological characteristics and short-term and long-term adverse events (30-day and > 30 days) were recorded and evaluated.No significant differences were noted between the 2 groups as regards demographics, comorbidity profiles, or initial feature of CTA. The incidence of true lumen compression was found to be significantly lower in the MCAD group compared with the DCAD group (8.2% versus 20.8%, P < 0.05). During the 65.37 ± 40.06 months of follow-up, there were no statistically significant differences in terms of 30-day mortality or the incidence of early adverse events between the 2 groups. The incidence rates of 5-year cumulative freedom from all-cause mortality and 5-year cumulative freedom from AD-related mortality were not significantly different between the MCAD and DCAD groups, whereas the 5-year cumulative freedom from adverse events were lower in the MCAD group compared to DCAD group (51.1% versus 72.5%, P < 0.05). In multivariate Cox regression models, only age > 60 years, pleural effusion, branch involvement, and length of the stent were independent predictors of mortality, whereas age > 60 years, pulse, pleural effusion, true lumen compression, widest diameter of the descending aorta, branch involvement, and length of stent were independent predictors of adverse aortic events.No significant difference was noted between the MCAD and DCAD groups in the 5-year mortality following, whereas patients with MCAD were found to have significantly lower AD-related events than patients with DCAD in long-term follow-up.

Reconstructing missing streamflow data can be challenging when additional data are not available, and missing data imputation of real-world datasets to investigate how to ascertain the accuracy of imputation algorithms for these datasets are lacking. This study investigated the necessary complexity of missing data reconstruction schemes to obtain the relevant results for a real-world single station streamflow observation to facilitate its further use. This investigation was implemented by applying different missing data mechanisms spanning from univariate algorithms to multiple imputation methods accustomed to multivariate data taking time as an explicit variable. The performance accuracy of these schemes was assessed using the total error measurement (TEM) and a recommended localized error measurement (LEM) in this study. The results show that univariate missing value algorithms, which are specially developed to handle univariate time series, provide satisfactory results, but the ones which provide the best results are usually time and computationally intensive. Also, multiple imputation algorithms which consider the surrounding observed values and/or which can understand the characteristics of the data provide similar results to the univariate missing data algorithms and, in some cases, perform better without the added time and computational downsides when time is taken as an explicit variable. Furthermore, the LEM would be especially useful when the missing data are in specific portions of the dataset or where very large gaps of 'missingness' occur. Finally, proper handling of missing values of real-world hydroclimatic datasets depends on imputing and extensive study of the particular dataset to be imputed.

Background: 5-aminoketovaleric acid, as a precursor of the strong photosensitizer protoporphyrin IX (PpIX), mainly enters the mitochondria after entering the cell, and the formed PpIX is also mainly localized in the mitochondria. So at present the research on the mechanism of 5-aminoketovalerate photodynamic therapy (ALA-PDT) mainly focuses on its impact on mitochondria. There are few reports on whether ALA-PAT can affect the endoplasmic reticulum and trigger endoplasmic reticulum stress (ERS)., Aims/objectives: Here we investigated the effects of ALA-PDT on endoplasmic reticulum and its underlying mechanisms in high-risk human papillomavirus (HR-HPV) infection., Materials and Methods: The human cervical cancer cell line HeLa (containing whole genome of HR-HPV18) was treated with ALAPDT, and cell viability, ROS production, the level of Ca2+ in the cytoplasm and apoptosis were evaluated by CCK8, immunofluorescence and flow cytometry, respectively. The protein expression of the markers of ERS and autophagy and CamKKβ-AMPK pathway was examined by western blot., Results: The results showed that ALA-PDT inhibited cell viability of HeLa cells in vitro; ALA-PDT induced autophagy in HeLa cells ; ALA-PDT induced autophagy via the Ca2+-CamKKβ-AMPK pathway, which could be suppressed by the inhibition of ERS;ALA-PDT induced ERS-specific apoptosis via the activation of caspase 12., Conclusions: Our study demonstrated that ALA-PDT could exert a killing effect by inducing HeLa cell apoptosis, including endoplasmic reticulum-specific apoptosis. Meanwhile, ERS via the Ca2+ -CamKKβ-AMPK pathway promoted the occurrence of autophagy in HeLa cells. Inhibition of autophagy could increase the apoptosis rate of HeLa cells after ALA-PDT, suggesting that autophagy may be one of the mechanisms of PDT resistance; The Ca2+-CamKKβ-AMPK pathway and autophagy may be targets to improve the killing effect of ALA-PDT in treating HR-HPV infection., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The therapeutic effect of dihydroartemisinin (DHA) against cutaneous squamous cell carcinoma (cSCC) has been previously demonstrated; however, the underlying mechanism remains unclear. This study sought to verify the therapeutic effect of DHA against cSCC and explore its underlying mechanism in A431 cSCC cells. This study reported that DHA inhibited A431 cells proliferation in a time- and concentration-dependent manner and promoted A431 cells apoptosis. Moreover, DHA inhibited the invasion and migration of A431 cells. Mechanistically, DHA promoted autophagy and inhibited activation of the absent in melanoma 2 (AIM2) inflammasome pathway and NF-κB/HIF-1α/VEGF pathway. Treatment of A431 cells with the mTOR inhibitor, and autophagy promoter, rapamycin also inhibited these two pathways. In conclusion, DHA inhibited activation of the AIM2 inflammasome pathway and NF-κB/HIF-1α/VEGF pathway by promoting autophagy in A431 cells, thus accounting for its therapeutic effect. Induction of autophagy by DHA may be mediated by inhibiting the mTOR pathway and promoting reactive oxygen species production., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Ovarian cancer (OC) is a leading cause of death in gynecological malignancies worldwide. Multitudinous studies have suggested the potential of circulating tumor DNA (ctDNA), circulating microRNAs (miRNAs), and long non-coding RNAs (lncRNAs) as novel diagnostic molecular biomarkers for OC. Here, we include three updated meta-analysis methods using different molecular biomarkers to evaluate their discriminative value in OC diagnosis., Methods: We conducted three meta-analyses after searching different databases, and 23 eligible articles, including 8 concerning ctDNA, 11 concerning miRNAs, and 4 concerning lncRNAs, were found. Further, we pooled data concerning the sensitivity, specificity, and other indicators of accuracy for ctDNA/miRNAs/lncRNAs in the diagnosis of OC. The heterogeneity was further explored by meta-regressions and subgroup analyses, and Deeks' funnel plots were used to measure the publication bias of these three meta-analyses., Results: In all, this meta-analysis included 1732 OC patients and 3958 controls. The sensitivity of ctDNA for OC diagnosis was superior to that of lncRNA and miRNA (84% vs. 81% vs. 78%). Moreover, the specificity and area under the receiver-operating characteristic (ROC) curve (AUC) of ctDNA were 91% and 94%, which were significantly higher than those of miRNA and lncRNAs (78% and 85%; 78% and 86%, respectively). No significant difference was observed among the two meta-analyses of ctDNA and lncRNA (P > 0.05) with regard to publication bias, while the meta-analysis of miRNA observed a significantly small publication bias (P < 0.05)., Conclusion: ctDNA/miRNAs/lncRNAs may be promising molecular biomarkers for OC diagnosis. Further large-scale studies are needed to verify the potential applicability of ctDNA/miRNAs/lncRNAs molecular signatures alone or in combination as diagnostic molecular biomarkers for OC., Competing Interests: The authors have declared that no competing interests exist.

Four lanthanide metal-organic frameworks (Ln-MOFs), namely {[Me 2 NH 2 ][LnL]·2H 2 O} n (Ln = Eu 1 , Tb 2 , Dy 3 , Gd 4 ), have been constructed from a new tetradentate ligand 1-(3,5-dicarboxylatobenzyl)-3,5-pyrazole dicarboxylic acid (H 4 L). These isostructural Ln-MOFs, crystallizing in the monoclinic P 2 1 /c space group, feature a 3D structure with 7.5 Å × 9.8 Å channels along the b axis and the point symbol of {4 10 .6 14 .8 4 } {4 5 .6} 2 . The framework shows high air and hydrolytic stability, which can keep stable after exposed to humid air for 30 days or immersed in water for seven days. Four MOFs with different lanthanide ions (Eu 3+ , Tb 3+ , Dy 3+ , and Gd 3+ ) ions exhibit red, green, yellow, and blue emissions, respectively. The Tb-MOF emitting bright green luminescence can selectively and rapidly (<40 s) detect Fe 3+ in aqueous media via a fluorescence quenching effect. The detection shows excellent anti-inference ability toward many other cations and can be easily recognized by naked eyes. In addition, it can also be utilized as a rapid fluorescent sensor to detect acetone solvent as well as acetone vapor. Similar results of sensing experiments were observed from Eu-MOF. The sensing mechanism are further discussed.

Aims and Background: High-risk human papillomavirus (HR-HPV) infection has been confirmed to be highly related to diseases such as Bowenoid papulosis, cervical cancer, and cervical intraepithelial neoplasia. 5-aminolevulinic acid-mediated PDT (ALA-PDT) has been used in a variety of HR-HPV infection-related diseases. Dihydroartemisinin (DHA) is one of artemisinin derivatives, and has inhibitory effects on a variety of cancer cells. For now, there is no published study focusing on the combination use of ALA-PDT with DHA to improve clinical efficacy of HR-HPV infection-related diseases. So in this study, we will examine the effectiveness of combined treatment of ALA-PDT and DHA for HR-HPV infection as well as its underlying mechanism., Methods: The human cervical cancer cell line HeLa (containing whole genome of HR-HPV18) was treated with ALA-PDT or/and DHA, and cell viability, long proliferation, ROS production and apoptosis were evaluated by CCK8, colony-forming assay, immunofluorescence and flow cytometry, respectively. The protein expression of NF-κB-HIF-1α-VEGF pathway and NRF2-HO-1 pathway was examined by western blot., Results: The results showed that DHA could enhance the effect of ALA-PDT on cell viability long proliferation, ROS production and apoptosis in HeLa cells. We also found that DHA inhibited NF-κB-HIF-1α-VEGF pathway which was activated by ALA-PDT. Besides, ALA-PDT combined with DHA activated NRF2-HO-1 pathway., Conclusion: Although the NRF2 - NO-1 pathway as a resistance mechanism remains unresolved, DHA has the potential to enhance the effect of ALA-PDT for HPV infection-related diseases through inhibiting NF-κB - HIF-1α - VEGF pathway., (Copyright © 2020 Elsevier B.V. All rights reserved.)

This report describes a PTCH1 c.1804C > T (p.Arg602*) mutation causing a Chinese nevoid basal cell carcinoma syndrome (NBCCS) with multiple basal cell carcinoma (BCC) phenotype. Multiple modalities including microwave ablation, photodynamic therapy, and excision surgery have a good respond to the NBCCS. The current results broaden the spectrum of PTCH1 mutations responsible for NBCCS., (Copyright © 2020. Published by Elsevier B.V.)

The identification of unit hydrographs and component flows from rainfall, evapotranspiration and streamflow data (IHACRES) model has been proven to be an efficient yet basic model to simulate rainfall-runoff processes due to the difficulty in obtaining the comprehensive data required by physical models, especially in data-scarce, semi-arid regions. The success of a calibration process is tremendously dependent on the objective function chosen. However, objective functions have been applied largely in over daily and monthly scales and seldom over sub-daily scales. This study, therefore, implements the IHACRES model using 'hydromad' in R to simulate flood events with data limitations in Zhidan, a semi-arid catchment in China. We apply objective function constraints by time aggregating the commonly used Nash-Sutcliffe efficiency into daily and hourly scales to investigate the influence of objective function constraints on the model performance and the general capability of the IHACRES model to simulate flood events in the study watershed. The results of the study demonstrated the advantage of the finer time-scaled hourly objective function over its daily counterpart in simulating runoff for the selected flood events. The results also indicated that the IHACRES model performed extremely well in the Zhidan watershed, presenting the feasibility of the use of the IHACRES model to simulate flood events in data scarce, semi-arid regions.

Vascular endothelial growth factor A (VEGFA), which plays a key role in angiogenesis, is composed of many isoforms. Distinct VEGFA isoforms are generated by alternative splicing of VEGFA mRNA and named as VEGF xxx , where xxx represents the number of amino acids present in the final protein sequence. These isoforms have opponent pro- and antiangiogenic effects. VEGF-Ax, an additional isoform containing a 22-amino-acid extension in the COOH terminus, arising from VEGFA mRNA, programmed translational readthrough. The function of VEGF-Ax is not clear, especially the conclusion that VEGF-Ax regulates angiogenesis is contradictory. Thus, we investigated the effect of VEGF-Ax on differentiation and angiogenesis of rat bone marrow mesenchymal stem cells (BMMSCs). The results showed that VEGF-Ax could promote the proliferation and migration of BMMSCs, stimulate the differentiation of BMMSCs into endothelial cell-like cells, and protect BMMSCs from endoplasmic reticulum stress-induced apoptosis.

Background: This study aimed to evaluate the effects of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) on the improvement of symptoms and recurrence rate in patients with vulvar lichen sclerosus (VLS) and observe its side effects., Methods: The symptom scores before and after photodynamic therapy (PDT) in 13 enrolled patients with VLS were analyzed retrospectively. All patients were followed-up for at least 6 months to evaluate the recurrence rate after PDT. The patients were treated with PDT only during the study period. During the PDT treatment, a 20 % 5-aminolevulinic acid solution was applied to the lesions and marginal areas for 3 h, and the entire area was then irradiated with 635 nm red light of 80 J/cm 2 at 80 mW/cm 2 for 30 min., Results: In this study, the effective rate of PDT was 92.31 %. Lesions recurred in two patients at 6 months after PDT. Post-treatment, the total subjective, total objective, and the Dermatological Life Quality Index scores changed from 11.4, 4.3, and 13.4 at baseline to 4.9, 2, and 5.9, respectively. The difference was statistically significant (p <0.05). PDT was mildly toxic in most patients., Conclusions: ALA-PDT is a safe and effective method for the treatment of VLS, and the therapeutic effects can be maintained for at least 3 months. The therapeutic effects may decrease during the 3-6-month period after PDT., Competing Interests: Declaration of Competing Interest None., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Bowenoid papulosis is a polymorphic papular disease that occurs on the external genital area. We investigated the efficacy of 5-aminolevulinic acid-mediated photodynamic therapyin the treatment of Bowenoid papulosis., Methods: We investigated 200 Bowenoid papulosis cases from the Department of Dermatology and Venereology of Nanfang Hospital in 2016-2018. Biopsies were performed from Bowenoid papulosis lesions before treatment. The patients were divided into two groups: 100 patients each in the 5-aminolevulinic acid-mediated photodynamic therapy and control groups(radiofrequency cauterisation, microwave ablation, and surgical resection groups). Differences in lesion clearance, recurrence rate, and patient satisfaction after treatment were evaluated., Results: Photodynamic therapy sessions for multifocal Bowenoid papulosis were more frequent than those for monofocal lesions. All lesions in the 5-aminolevulinic acid-mediated photodynamic therapy group were cleared after photodynamic therapy, with no recurrence at the 1-year follow-up; however, 20 (20.0 %) patients in the control showed recurrence after 1 year. Only 5patients in the photodynamic group were unsatisfied with the treatment cost and 34 patients in the control group experienced short-term pain and scarring. The recurrence rate was significantly lower (P < 0.05) and patient satisfaction was higher (P < 0.05) in the 5-aminolevulinic acid-mediated photodynamic therapy group than those in the control. The recurrence rate was significantly lower (P < 0.05) and patient satisfaction was higher (P < 0.05) in the 5-aminolevulinic acid-mediated photodynamic therapy group than those in the surgical resection group. The recurrence rate of lesions was significantly lower in the surgical resection group than that in the rest of the control group (P < 0.05). There was no difference in recurrence rate and patient satisfaction between the radiofrequency cauterisation and microwave ablation groups., Conclusions: 5-aminolevulinic acid-mediated photodynamic therapy for Bowenoid papulosis results in a low recurrence rate and high satisfaction., Competing Interests: Declaration of Competing Interest None., (Copyright © 2019. Published by Elsevier B.V.)