DNA methylation of microRNA-365-1 induces apoptosis of hair follicle stem cells by targeting DAP3.

Background: DNA methylation is a crucial epigenetic alteration involved in diverse biological processes and diseases. Nevertheless, the precise role of DNA methylation in chemotherapeutic drug-induced alopecia remains unclear. This study examined the role and novel processes of DNA methylation in regulating of chemotherapeutic drug-induced alopecia. Methods: A mouse model of cyclophosphamide (CTX)-induced alopecia was established. Hematoxylin-eosin staining and immunohistochemical staining for the Ki67 proportion and a mitochondrial membrane potential assay (JC-1) were performed to assess the structural integrity and proliferative efficiency of the hair follicle stem cells (HFSCs). Immunofluorescence staining and real-time fluorescence quantitative PCR (RT-qPCR) were performed to determine the expression levels of key HFSC markers, namely Lgr5, CD49f, Sox9, CD200, and FZD10. Differential DNA methylation levels between the normal and CTX-induced model groups were determined through simple methylation sequencing and analyzed using bioinformatics tools. The expression levels of miR-365-1, apoptosis markers, and DAP3 were detected through RT-qPCR and western blotting. In parallel, primary mouse HFSCs were extracted and used as a cell model, which was constructed using 4-hydroperoxycyclophosphamide. The luciferase reporter gene assay was conducted to confirm miR-365-1 binding to DAP3. To measure the expression of relevant indicators, superoxide dismutase (SOD) and malondialdehyde (MDA) kits were used. Methylation-specific PCR (MS-PCR) was performed to determine DNA methylation levels. The regulatory relationship within HFSCs was confirmed through plasmid overexpression of miR-365-1 and DAP3. Result: In the alopecia areata model, a substantial number of apoptotic cells were observed within the hair follicles on the mouse backs. Immunofluorescence staining revealed that the expression of HFSC markers significantly reduced in the CTX group. Both RT-qPCR and western blotting demonstrated a noteworthy difference in DNA methyltransferase expression. Simple methylation sequencing unveiled that DNA methylation substantially increased within the dorsal skin of the CTX group. Subsequent screening identified miR-365-1 as the most differentially expressed miRNA. miR-365-1 was predicted and confirmed to bind to the target gene DAP3. In the CTX group, SOD and ATP expression markedly reduced, whereas MDA levels were significantly elevated. Cellular investigations revealed 4-HC-induced cell cycle arrest and decreased expression of HFSC markers. MS-PCR indicated hypermethylation modification of miR-365-1 in the 4-HC-induced HFSCs. The luciferase reporter gene experiment confirmed the binding of miR-365-1 to the DAP3 promoter region. miR-365-1 overexpression dramatically reduced apoptotic protein expression in the HFSCs. However, this effect was slightly reversed after DAP3 overexpression in lentivirus. Conclusion: This study explored the occurrence of miR-365-1 DNA methylation in chemotherapeutic drug-induced alopecia. The results unveiled that miR-365-1 reduces cell apoptosis by targeting DAP3 in HFSCs, thereby revealing the role of DNA methylation of the miR-365-1 promoter in chemotherapeutic drug-induced alopecia.

Rapid analysis of Radix Astragali using a portable Raman spectrometer with 1064-nm laser excitation and data fusion with PLS-DA.

Radix Astragali is a medicinal herb with various physiological activities. There were high similarities among Radix Astragali samples from different regions owing to similarities in their major chemical compositions. Raman spectroscopy is a non-invasive and non-des- tructive technique that can be used in in-situ analysis of herbal samples. Dispersive Raman scattering, excited at 1064 nm, produced minimal fluorescence background and facilitated easy detection of the weak Raman signal. By moving the portable Raman probe point-by- point from the centre of the Radix Astragali sample to the margin, the spectral fingerprints, composed of dozens of Raman spectra representing the entire Radix Astragali samples, were obtained. Principal component analysis and partial least squares discriminant analysis (PLS-DA) were applied to the Radix Astragali spectral data to compare classification results, leading to efficient discrimination between genuine and counterfeit products. Furthermore, based on the PLS-DA model using data fusion combined with different pre- processing methods, the samples from Shanxi Province were separated from those belonging to other habitats. The as-proposed combination method can effectively improve the recognition rate and accuracy of identification of herbal samples, which can be a valuable tool for the identification of genuine medicinal herbs with uneven qualities and various origins.

Machine learning models for early prediction of potassium lowering effectiveness and adverse events in patients with hyperkalemia.

The aim of this study was to develop a model for early prediction of adverse events and treatment effectiveness in patients with hyperkalemia. We collected clinical data from patients with hyperkalemia in the First Hospital of Zhejiang University School of Medicine between 2015 and 2021. The least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression were used to analyze the predictors on the full dataset. We randomly divided the data into a training group and a validation group, and used LASSO to filter variables in the training set. Six machine learning methods were used to develop the models. The best model was selected based on the area under the curve (AUC). Shapley additive exPlanations (SHAP) values were used to explain the best model. A total of 1074 patients with hyperkalemia were finally enrolled. Diastolic blood pressure (DBP), breathing, oxygen saturation (SPO2), Glasgow coma score (GCS), liver disease, oliguria, blood sodium, international standardized ratio (ISR), and initial blood potassium were the predictors of the occurrence of adverse events; peripheral edema, estimated glomerular filtration rate (eGFR), blood sodium, actual base residual, and initial blood potassium were the predictors of therapeutic effect. Extreme gradient boosting (XGBoost) model achieved the best performance (adverse events: AUC = 0.87; therapeutic effect: AUC = 0.75). A model based on clinical characteristics was developed and validated with good performance.

Identification of IRF1 as a Novel Pyroptosis-Related Prognostic Biomarker of Atopic Dermatitis.

Purpose: The aim of this study was to characterize key biomarkers associated with pyroptosis in atopic dermatitis (AD). Materials and methods: To identify the differentially expressed pyroptosis-related genes (DEPRGs), the gene expression profiles GSE16161 and GSE32924 from the Gene Expression Omnibus (GEO) database were utilized. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted to determine the potential biological functions and involved pathways. Furthermore, protein-protein interaction network analyses were performed to identify hub genes. The types and proportions of infiltrating immune cells were detected by immune filtration analysis using CIBERSORT. A 12-axis competing endogenous RNA (ceRNA) network was constructed utilizing the miRNet database. Immunohistochemistry (IHC) further validated the differential expression of a key gene IRF1 in the skin tissues collected from AD patients. The collection of skin tissue from human subjects in this study were reviewed and approved by the IRB of Yueyang Integrated Chinese and Western Medicine Hospital (KYSKSB2020-125). Results: The study identified a total of 76 DEPRGs, which were enriched in genes associated with the inflammatory response and immune regulation. There was a higher percentage of activated dendritic cells and a lower percentage of resting mast cells in AD samples. PVT1 expression was associated with upregulation of hub genes including CXCL8, IRF1, MKI67, and TP53 in the ceRNA network and was correlated with activated dendritic cells in AD. As a transcription factor, IRF1 could regulate the production of downstream inflammatory factors. The IHC study revealed that IRF1 was overexpressed in the skin tissues of AD patients, which were consistent with the results of the bioinformatic study. Conclusions: IRF1 and its related genes were identified as key pyroptosis-related biomarkers in AD, which is a crucial pathway in the pathogenesis of AD.

Lathyrane diterpenoids from Euphorbia lathyris induce cell-cycle arrest and apoptosis in human hypertrophic scar cells.

One new lathyrane-type diterpenoid, euphlathin A (1), and 11 known analogues (2-12), were isolated from the fruits of Euphorbia lathyris. Their structures were elucidated by spectroscopic data. The absolute configurations of 1 were established by single-crystal X-ray crystallography. All diterpenoids (1-12) were evaluated for antiproliferative activity against the human hypertrophic scar (HTS) cells. Compound 1 exhibited significantly against HTS cells growth with an IC50 value of 6.33 µM. Morphological features of apoptosis were evaluated in 1-treated HTS cells. Wound healing assays indicated that 1 significantly inhibited the migration of HTS at 24 h and 48 h. Compound 1 effectively induced apoptosis of HTS, which was associated with G2/M or S phase cell cycle arrest. Flow cytometric analysis showed that the treatment by 1 significantly induced HTS cell apoptosis in a dose-dependent manner. Overall, euphlathin A (1) has the potential to be a therapeutic agent for the treatment of hyperplastic scar therapy.

Constrained Model Predictive Control Based on Event Triggering for the Rare Earth Extraction Process.

Since the reagent dosage is manually adjusted according to work conditions, an event-triggered constrained model predictive control is proposed for rare earth extraction. First, the linear predictive system, based on a state space model, is established. Subsequently, the feedback correction link is fine-tuned to reduce the prediction error. Following this, an objective optimization function, incorporating input and output constraints, is introduced to calculate the appropriate reagent dosage. Finally, an event-triggering mechanism, underpinned by a designated threshold, is designed to update the controller. Simulation outcomes substantiate the efficacy of the proposed approach.

Effect of Chromium Carbide Addition on the Microstructures and Properties in Dual Carbide Phases Reinforced Ni-Based Composite Coatings by Plasma Cladding.

Cr3C2-modified NiCr-TiC composite coatings were prepared using the plasma spraying technique for different Cr3C2 contents on the microstructure and the properties of the Ni-based TiC cladding layer were investigated. The microstructures of the coatings were characterized using scanning electron microscopy, and the friction and wear performance of the coating was evaluated by the wear tests. The results revealed that the surfaces of the Cr3C2-modified NiCr-TiC composite coatings with varying Cr3C2 contents were dense and smooth. TiC was uniformly distributed throughout the entire coating, forming a gradient interface between the binder phase of the Ni-based alloy and the hard phase of TiC. At high temperatures, Cr3C2 decomposes, with some chromium diffusing and forming complex carbides around TiC, some chromium solubilizes with Fe, Ni, and other elements. An increase in chromium carbide content leads to an upward trend in hardness. The measured hardness of the coatings ranged from 600 to 850 HV3 and tended to increase with increasing Cr3C2 content. When the mass fraction of Cr3C2 reached 30%, the hardness increased to 850 HV3, and the cracks and defects were observed in the coating, resulting in a wear resistance decline.

Development and validation of a predictive model for the assessment of potassium-lowering treatment among hyperkalemia patients.

BACKGROUND: Hyperkalemia is common among patients in emergency department and is associated with mortality. While, there is a lack of good evaluation and prediction methods for the efficacy of potassium-lowering treatment, making the drug dosage adjustment quite difficult. We aimed to develop a predictive model to provide early forecasting of treating effects for hyperkalemia patients. METHODS: Around 80% of hyperkalemia patients (n=818) were randomly selected as the training dataset and the remaining 20% (n=196) as the validating dataset. According to the serum potassium (K+) levels after the first round of potassium-lowering treatment, patients were classified into the effective and ineffective groups. Multivariate logistic regression analyses were performed to develop a prediction model. The receiver operating characteristic (ROC) curve and calibration curve analysis were used for model validation. RESULTS: In the training dataset, 429 patients had favorable effects after treatment (effective group), and 389 had poor therapeutic outcomes (ineffective group). Patients in the ineffective group had a higher percentage of renal disease (P=0.007), peripheral edema (P<0.001), oliguria (P=0.001), or higher initial serum K+ level (P<0.001). The percentage of insulin usage was higher in the effective group than in the ineffective group (P=0.005). After multivariate logistic regression analysis, we found age, peripheral edema, oliguria, history of kidney transplantation, end-stage renal disease, insulin, and initial serum K+ were all independently associated with favorable treatment effects. CONCLUSION: The predictive model could provide early forecasting of therapeutic outcomes for hyperkalemia patients after drug treatment, which could help clinicians to identify hyperkalemia patients with high risk and adjust the dosage of medication for potassium-lowering.

Research on the wound healing effect of Shengji Huayu Formula ethanol extract-derived fractions in streptozotocin-induced diabetic ulcer rats.

BACKGROUND: Diabetic ulcer is a common complication of diabetes. It is characterized by a long-term disease course and high recurrence rate. Shengji Huayu Formula (SHF) is an effective formula for treating diabetic ulcers. However, the specific effective parts of SHF remain unclear. Clarifying the active polar site of SHF would be helpful to refine research on the components in SHF that promote wound healing. This research aims to focus on evaluating the activity of polar fractions. METHODS: A diabetic rat model was established by intraperitoneally injecting streptozotocin (STZ) and was adopted to confirm the therapeutic effect of SHF. Four different polarity parts were extracted from SHF and prepared into a cream to evaluate the activity. High-performance liquid chromatography (HPLC) was used to detect chemical constituents in chloroform extracts. RESULTS: It was discovered that dracorhodin, aloe-emodin, rhein, imperatorin, emodin, isoimperatorin, chrysophanol, physcion, and tanshinone IIA were the main components of the chloroform extract from SHF. The results revealed that chloroform extract could effectively accelerate diabetic wound healing by promoting collagen regeneration and epidermal repair. Chloroform extract of SHF could stimulate the generation of vascular endothelial growth factor (VEGF). The results are also indicated that the effective active fraction was the chloroform part, and the method of detecting the main chemical constituents in the active part was successfully established. CONCLUSION: SHF could improve diabetic ulcers by promoting granulation tissue synthesis. In this study, four polar parts (petroleum ether, chloroform, ethylacetate, n-butanol) were extracted from a 95% ethanol extract. In contrast, chloroform polar parts showed a higher wound closure rate, stimulated more collagen regeneration and promoted more production of vascular endothelial cells. In conclusion, the chloroform extract of SHF was the effective polar part in ameliorating diabetic wound healing.

Multi-Delay Identification of Rare Earth Extraction Process Based on Improved Time-Correlation Analysis.

The rare earth extraction process has significant time delay characteristics, making it challenging to identify the time delay and establish an accurate mathematical model. This paper proposes a multi-delay identification method based on improved time-correlation analysis. Firstly, the data are preprocessed by grey relational analysis, and the time delay sequence and time-correlation data matrix are constructed. The time-correlation analysis matrix is defined, and the H∞ norm quantifies the correlation degree of the data sequence. Thus the multi-delay identification problem is transformed into an integer optimization problem. Secondly, an improved discrete state transition algorithm is used for optimization to obtain multi-delay. Finally, based on an Neodymium (Nd) component content model constructed by a wavelet neural network, the performance of the proposed method is compared with the unimproved time delay identification method and the model without an identification method. The results show that the proposed algorithm improves optimization accuracy, convergence speed, and stability. The performance of the component content model after time delay identification is significantly improved using the proposed method, which verifies its effectiveness in the time delay identification of the rare earth extraction process.

Abietic acid induces ferroptosis via the activation of the HO-1 pathway in bladder cancer cells.

BACKGROUND: Bladder cancer (BC) is a common urological malignancy that still lacks effective treatments. Abietic acid (AA) is an abietane diterpene that possesses various biological activities, including antitumor activity. This study aimed at evaluating the effects of AA on BC cells. MATERIALS AND METHODS: The 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) assay was used to assess the effects of AA on the viability of BC cells. Annexin-V and FITC staining was used to assess cellular death. The type of cell death was determined by the administration of various specific cell death inhibitors. Commercial kits were used to measure the levels of reactive oxygen species (ROS), intracellular iron, malondialdehyde (MDA), and glutathione (GSH). Real-time polymerase chain reaction (RT-PCR) and western blot analysis were used to assay mRNA and protein levels, respectively. The role of glutathione peroxidase 4 (GPX4) in the antitumor effects of AA was evaluated using the forced expression of GPX4 in BC cells. The impact of HO-1 on the antitumor effects of AA was examined by gene silencing and pharmacological inhibition of the protein. Finally, the antitumor effects of AA were evaluated in xenograft models. RESULTS: AA selectively inhibited the viability of BC cells but not normal cells. AA-induced ferroptosis in BC cells was evidenced by the upregulation of ROS, intracellular iron, and MDA. AA treatment led to the downregulation of GPX4 and the upregulation of HO-1 in BC cells. Forced expression of GPX4 or inhibition of HO-1 resulted in decreased ferroptosis triggered by AA in BC cells. AA also showed synergistic effects with various chemotherapeutic agents against BC and inhibited the growth of BC cells in vivo. CONCLUSION: This study revealed AA-induced ferroptosis in BC cells both in vitro and in vivo. AA might be applied as a promising agent for the treatment of BC.

Case Report: An extremely rare penile shrapnel injury.

Penile shrapnel injuries are an exceedingly rare occurrence and a medical emergency. Herein, we present a case of penile shrapnel wounds in an adolescent male and discuss the management and complications associated with penetrating injuries to penile. We reported that an 18-year-old Chinese armed police soldier underwent debridement, shrapnel removal and suturing under spinal anesthesia. Six days postoperatively, he was discharged from the hospital smoothly. The patient reported normal erectile function and urination following discharge. With a follow-up of three months, the patient exhibited no symptoms of dysuria or erectile dysfunction. It is explicitly stated that prompt surgery intervention described in this report resulted in optimal prognosis. Penile shrapnel injury is a rare phenomenon typically associated with emergency drill and military training involving explosive shells. With regard to penetrating penile injury, timely surgical exploration is essential because it avoids penile plaque formation, penile fibrosis and angulation, and accelerates the return to erectile and urination function.

Effectiveness of traditional Chinese medicine preparations for facial seborrheic dermatitis: case reports.

Facial seborrheic dermatitis is a chronic skin condition that presents as erythematous scaly dermatitis and has a detrimental effect on the patient's quality of life. The purpose of this article is to present successful treatment of two male patients with face seborrheic dermatitis, one aged 50 and the other aged 56, who developed facial seborrheic dermatitis following facial erythema eruptions. We diagnosed it as face seborrheic dermatitis based on the patients' initial appearances and the location of the erythema during the episode. The previous doctor diagnosed the patients' facial symptoms as related to allergies or infections; therefore, they were treated with long-term anti-inflammatory (tacrolimus) and antiallergic medications (loratadine) throughout the disease's early stages. Erythema of the face was recurring and recalcitrant. Their facial skin lesions vanished after one week of Chinese herbal medicine treatment along with warming yang therapy. The application of the principle of warming the kidney yang to the treatment of face seborrheic dermatitis produced favorable results. This may be an advantageous adjunct to the treatment of recurrent seborrheic dermatitis of the face. High-performance liquid chromatography coupled with electrospray mass spectrometry (HPLC/ESI-MS) was used to determine the primary components of the Chinese herbal formula "adjusted Shen-Liu-Wei (ASLW)," which has six natural substances as its primary components. As a result, we believe that the Chinese herbal compound ASLW might be a viable alternative for symptom relief and successful treatment of face seborrheic dermatitis.

Development and validation of a nomogram model for predicting the risk of gallstone recurrence after gallbladder-preserving surgery.

BACKGROUND: The high incidence of gallstone recurrence was a major concern for laparoscopic gallbladder-preserving surgery. This study aimed to investigate the risk factors for gallstone recurrence after gallbladder-preserving surgery and to establish an individualized nomogram model to predict the risk of gallstone recurrence. METHODS: The clinicopathological and follow-up data of 183 patients who were initially diagnosed with gallstones and treated with gallbladder-preserving surgery at our hospital from January 2012 to January 2019 were retrospectively collected. The independent predictive factors for gallstone recurrence following gallbladder-preserving surgery were identified by multivariate logistic regression analysis. A nomogram model for the prediction of gallstone recurrence was constructed based on the selected variables. The C-index, receiver operating characteristic (ROC) curve and calibration curve were used to evaluate the predictive power of the nomogram model for gallstone recurrence. RESULTS: During the follow-up period, a total of 65 patients experienced gallstone recurrence, and the recurrence rate was 35.5%. Multivariate logistic regression analysis revealed that the course of gallstones > 2 years [odds ratio (OR) = 2.567, 95% confidence interval (CI): 1.270-5.187, P = 0.009], symptomatic gallstones (OR = 2.589, 95% CI: 1.059-6.329, P = 0.037), multiple gallstones (OR = 2.436, 95% CI: 1.133-5.237, P = 0.023), history of acute cholecystitis (OR = 2.778, 95% CI: 1.178-6.549, P = 0.020) and a greasy diet (OR = 2.319, 95% CI: 1.186-4.535, P = 0.014) were independent risk factors for gallstone recurrence after gallbladder-preserving surgery. A nomogram model for predicting the recurrence of gallstones was established based on the above five variables. The results showed that the C-index of the nomogram model was 0.692, suggesting it was valuable to predict gallstone recurrence. Moreover, the calibration curve showed good consistency between the predicted probability and actual probability. CONCLUSIONS: The nomogram model for the prediction of gallstone recurrence might help clinicians develop a proper treatment strategy for patients with gallstones. Gallbladder-preserving surgery should be cautiously considered for patients with high recurrence risks.

Hepatitis B virus promotes hepatocellular carcinoma development by activating GP73 to repress the innate immune response.

BACKGROUND: Hepatitis B virus (HBV) causes acute and chronic infection in the clinic. Hepatocellular carcinoma (HCC) is closely linked to HBV infection. Serum Golgi protein 73 (GP73) increases during HBV infection. However, the role of GP73 during HBV infection and the occurrence of HBV-related HCC is still poorly understood. METHODS: The underlying role of HBV-induced GP73 in regulating HCC development was investigated in this study. GP73 expression in HBV-related clinical HCC tissues and in HBV-infected hepatoma cells and primary human hepatocytes was evaluated by immunohistochemistry, ELISAs, Western blotting and quantitative real-time PCR (qRT-PCR) analysis. Tumorigenicity of GP73 overexpressed cells was detected by flow cytometry, qRT-PCR, xenograft nude mouse analyses and sphere formation assays. The effects of GP73 and HBV infection on host innate immune responses in hepatocytes were further investigated by Western blotting and qRT-PCR analysis. RESULTS: Initially, we confirmed that HBV-positive HCC tissues had significantly higher expression of GP73. Ectopic expression of the HBV gene could induce GP73 expression in primary human hepatocytes and hepatoma cells in vitro. In addition, we discovered that GP73 promotes HCC in both normal liver cells and hepatoma cells. We also found that ectopic expression of HBV genes increases GP73 expression, suppressing the host's innate immune responses in hepatocytes. CONCLUSIONS: Our results demonstrate that HBV facilitates HCC development by activating GP73 to repress the host's innate immune response. This study adds to our understanding of the pathogenesis of HBV infection-induced HCC. The findings also provide preclinical support for GP73 as a potential HCC prevention or treatment target.

Phellopterin cream exerts an anti-inflammatory effect that facilitates diabetes-associated cutaneous wound healing via SIRT1.

BACKGROUND: Diabetic ulcers, which are characterized by chronic nonhealing wounds with a long-lasting inflammatory state, are a typical symptom in individuals with diabetes, and there is still no effective treatment for these lesions. Angelica dahurica plays a critical role in inflammatory diseases. Among numerous monomeric compounds, phellopterin has been shown to have anti-inflammatory properties. PURPOSE: To research the bioactive constituents in Angelica dahurica and their mechanism of action in treating diabetic ulcers. STUDY DESIGN: Chemical research of Angelica dahurica led to the identification of a new coumarin, dahuricoumarin A (1), along with seven known compounds (2 - 8). All compounds were tested for anti-inflammatory activity, and phellopterin, compound (3), significantly decreased the expression of intercellular cell adhesion molecule-1 (ICAM-1), a representative indicator of inflammation. Phellopterin can also increase SIRT1 protein, a key target for inflammation. In our research, we confirmed the anti-inflammatory effects of phellopterin on diabetic ulcers and explored the underlying mechanism of action. METHODS: The expression of IFN-γ, SIRT1, and ICAM-1 in human diabetic ulcer tissues was studied using immunohistochemistry. Streptozotocin was used to induce a diabetic model in C57BL/6J mice, and ulcers were surgically introduced. After phellopterin treatment, the skin lesions of diabetic mice were observed over a period of time. The protein and mRNA expression levels of SIRT1 and ICAM-1 were measured using H&E, qRT-PCR and immunohistochemical staining. A HaCaT cell inflammatory model was induced by IFN-γ. Using a lentiviral packaging technique, MTT assay, and Western blotting, the effect of phellopterin on the proliferation of HaCaT cells and the expression of ICAM-1 was evaluated under normal and SIRT1 knockdown conditions. RESULTS: High levels of ICAM-1 and IFN-γ were identified, but low levels of SIRT1 were found in human diabetic ulcer tissues, and phellopterin showed therapeutic benefits in the healing process by attenuating chronic inflammation and promoting re-epithelialization, along with SIRT1 upregulation and ICAM-1 downregulation. However, inhibiting SIRT1 reversed its proliferative and anti-inflammatory effects. CONCLUSION: In vitro and in vivo, phellopterin exerts anti-inflammatory and proliferative effects that promote diabetic wound healing, and the potential mechanism depends on SIRT1.

Digital twin key technology on rare earth process.

Digital twin can be defined as a digital equivalent of an object of which it can mirror its behavior and status or virtual replicas of real physical entities in Cyberspace. To an extent, it also can simulate and predict the states of equipment or systems through smart algorithms and massive data. Hence, the digital twin is emerging used in intelligent manufacturing Systems in real-time and predicting system failure and also has introduced into a variety of traditional industries such as construction, Agriculture. Rare earth production is a typical process industry, and its Extraction Process enjoys the top priority in the industry. However, the extraction process is usually characterized by nonlinear behavior, large time delays, and strong coupling of various process variables. In case of failures happened in the process, the whole line would be shut down. Therefore, the digital twin is introduced into the design of process simulation to promote the efficiency and intelligent level of the Extraction Process. This paper proposes the techniques to build the rare earth digital twin such as soft measurement of component content, component content process simulation, control optimization strategy, and virtual workshop, etc. At the end, the validity of the model is verified, and a case study is conducted to verify the feasibility of the whole Digital twin framework.

Mivebresib synergized with PZ703b, a novel Bcl-xl PROTAC degrader, induces apoptosis in bladder cancer cells via the mitochondrial pathway.

Bladder cancer is a common urinary cancer that still lacks effective treatments. In the present study, we evaluated the effect of BET inhibitor, mivebresib, in combination with PZ703b, a Bcl-xl PROTAC, on apoptosis in bladder cancer cells. The results revealed that mivebresib and PZ703b synergistically decreased the viabilities of bladder cancer cells. Co-treatment of mivebresib and PZ703b induced apoptosis in bladder cancer cells via the mitochondrial pathway in a caspase-dependent manner. Mechanistically, mivebresib and PZ703b treatment inhibited the expression of Mcl-1 and Bcl-xl, accompanied by upregulation of Bim. Hence, co-treatment of mivebresib and PZ703b rebalanced the level of pro- and anti-apoptotic Bcl-2 proteins in cells. Further investigations showed that forced expression of Mcl-1 or Bcl-xl markedly protected bladder cancer cells from apoptosis induced by combination treatment of mivebresib and PZ703b. In addition, knockdown of Bim also inhibited the cell death induced by mivebresib/PZ703b in bladder cancer cells. In summary, our findings reveal that the combination treatment of mivebresib and PZ703b represents a novel promising strategy to treat bladder cancer.

Rhein promotes the proliferation of keratinocytes by targeting oestrogen receptors for skin ulcer treatment.

BACKGROUND: The Sheng-ji Hua-yu (SJHY) formula is a quite effective Traditional Chinese Medicines (TCM) in the treatment of delayed diabetic wounds. Previous research has shown that the SJHY formula has significant anti-inflammatory and wound-healing effects, but the precise mechanism remains unknown. The purpose of this study was to evaluate the effects of rhein, a compound extracted from SJHY formula, in keratinocytes and to investigate the underlying mechanisms. METHODS: Microscale thermophoresis (MST) technology was used to confirm that rhein binds directly to oestrogen receptors (ERs). Rhein was then used to treat keratinocytes in vitro. Cell cycle and proliferation analysis, Real-time polymerase chain reaction (RT-PCR) and Western-blot were conducted. RESULTS: Rhein increased the proportion of cells in the S phase of the cell cycle and promoted keratinocyte proliferation. ICI 182,780, an ER inhibitor, was also used to treat keratinocytes. The expression of c-myc mRNA and protein induced by rhein was antagonized by ICI 182,780, indicating that this induction is ER dependent. Intervention with ICI 182,780 had no effect on the upregulation of FosB and JunD, indicating that activator protein 1 (AP-1) members (FosB and JunD) are involved in rhein-induced c-myc mRNA and protein expression but does not require the ER. CONCLUSION: The present study found that rhein stimulates keratinocyte proliferation by activating the oestrogen signalling pathway via the oestrogen receptor, which induces the expression of c-myc in collaboration with FosB and JunD, thereby accelerating the process of re-epithelialization.