Abnormal metabolism in melanocytes participates in the activation of dendritic cell in halo nevus.

A comprehensive analysis of spatial transcriptomics was carried out to better understand the progress of halo nevus. We found that halo nevus was characterized by overactive immune responses, triggered by chemokines and dendritic cells (DCs), T cells, and macrophages. Consequently, we observed abnormal cell death, such as apoptosis and disulfidptosis in halo nevus, some were closely related to immunity. Interestingly, we identified aberrant metabolites such as uridine diphosphate glucose (UDP-G) within the halo nevus. UDP-G, accompanied by the infiltration of DCs and T cells, exhibited correlations with certain forms of cell death. Subsequent experiments confirmed that UDP-G was increased in vitiligo serum and could activate DCs. We also confirmed that oxidative response is an inducer of UDP-G. In summary, the immune response in halo nevus, including DC activation, was accompanied by abnormal cell death and metabolites. Especially, melanocyte-derived UDP-G may play a crucial role in DC activation.

How to improve smart emergency preparedness for natural disasters? ---- Evidence from the experience of ten pilot provinces in China for smart emergency.

The natural disasters faced by modern urban systems are complex, with multiple disaster-causing factors coexisting and secondary disasters occurring concurrently. With emergency management moving towards smart, natural disaster response has shifted from emergency-centered response to pre-disaster prevention. How to improve the government's natural disaster emergency preparedness has become an important issue that needs to be addressed. Based on the TOE (Technology-Organization-Environment) framework, the fsQCA method was used to explore the improvement path of emergency preparedness capacity of 10 pilot units in China to deal with natural disasters in 2020. Analyze the group effects and interrelationships of technology level, simultaneous supporting facilities, organizational construction, financial investment, external pressure, and social repercussions. The results show that: there exist four conditional groupings of high emergency preparedness in two modes. Two modes are organization-environment dual-drive and technology-organization-environment triple-drive, which have multiple concurrencies and follow the principle of consistent results. There are substitution effects in the conditional groupings of high emergency preparedness. There are causal asymmetries in the conditional groupings of high emergency preparedness and non-high emergency preparedness. This study aims to explore the smart emergency preparedness of ten pilot and to provide ideas for the overall development of "smart emergency response" and the improvement of emergency preparedness for natural disasters.

Macrophage migration inhibitory factor mediates skin aging via CD74: Insights from single-cell and bulk RNA sequencing data.

Cell-cell communication is crucial for regulating signaling and cellular function. However, the precise cellular and molecular changes remain poorly understood in skin aging. Based on single-cell and bulk RNA data, we explored the role of cell-cell ligand-receptor interaction in skin aging. We found that the macrophage migration inhibitory factor (MIF)/CD74 ligand-receptor complex was significantly upregulatedin aged skin, showing the predominant paracrine effect of keratinocytes on fibroblasts. Enrichment analysis and in vitro experiment revealed a close association of the activation of the MIF/CD74 with inflammatory pathways and immune response. Mechanistically, MIF/CD74 could significantly inhibit PPARγ protein, which thus significantly increased the degree of fibroblast senescence, and significantly up-regulated the expression of senescence-associated secretory phenotype (SASP) factors and FOS gene. Therefore, our study reveals that MIF/CD74 inhibits the activation of the PPAR signaling pathway, subsequently inducing the production of SASP factors and the upregulation of FOS expression, ultimately accelerating fibroblast senescence.

Three-dimensional N-doped carbon nanosheets loaded with heterostructured Ni/Ni3ZnC0.7 nanoparticles for selective and efficient CO2 reduction.

Electrocatalytic CO2 reduction (CO2RR) has emerged as a promising approach for converting CO2 into valuable chemicals and fuels to achieve a sustainable carbon cycle. However, the development of efficient electrocatalysts with high current densities and superior product selectivity remains a significant challenge. In this study, we present the synthesis of a porous nitrogen-doped carbon nanosheet loaded with heterostructured Ni/Ni3ZnC0.7 nanoparticles through a facile hydrothermal-calcination method (Ni/Ni3ZnC0.7-NC). Remarkably, the Ni/Ni3ZnC0.7-NC catalyst exhibits outstanding performance towards CO2RR in an H-cell, demonstrating a high CO faradaic efficiency of 92.47% and a current density (jCO) of 15.77 mA cm-2 at 0.87 V vs. RHE. To further explore its potential industrial applications, we constructed a flow cell and a rechargeable Zn-CO2 flow cell utilizing the Ni/Ni3ZnC0.7-NC catalyst as the cathode. Impressively, not only does the Ni/Ni3ZnC0.7-NC catalyst achieve an industrial high current density of 254 mA cm-2 at a voltage of -1.19 V vs. RHE in the flow cell, but it also exhibits a maximum power density of 4.2 mW cm-2 at 22 mA cm-2 in the Zn-CO2 flow cell, while maintaining excellent rechargeability. Density functional theory (DFT) calculations indicate that Ni/Ni3ZnC0.7-NC possesses more spontaneous reaction pathways for CO2 reduction to CO, owing to its heterogeneous structure in contrast to Ni3ZnC0.7-NC and Ni-NC. Consequently, Ni/Ni3ZnC0.7-NC demonstrates accelerated CO2RR reaction kinetics, resulting in improved catalytic activity and selectivity for CO2RR.

Decreased oxidative stress response and oxidant detoxification of skin during aging.

Oxidative stress plays an important role in the skin aging process; however, the mechanisms are not fully elucidated. Especially the changes in various types of skin cells with aging and the key oxidative stress-related genes that play a regulatory role are not clear. In this study, single-cell RNA sequencing data and microarray transcriptome data were used to explore the changes in oxidative stress response and oxidant detoxification capacity of skin cells during aging and oxidative stress-related genes potentially involved in regulating skin aging were searched. The oxidative stress response and oxidant detoxification ability were weakened in the elderly compared with those of the young. Among the different types of skin cells, keratinocytes, melanocytes, vascular endothelial cells, fibroblasts, and lymphatic endothelial cells exhibited a stronger oxidative stress response and oxidant detoxification ability, while immune cells exhibited a weaker oxidative stress response and detoxification capacity. During aging, the oxidative stress response and oxidant detoxification capacity of keratinocytes, fibroblasts, macrophages, and vascular endothelial cells were significantly weakened. Annexin A1 (ANXA1) and Apolipoprotein E (APOE) may be key oxidative stress-related genes affecting skin aging.

Isoliquiritigenin regulates the circ_0002860/miR-431-5p/RAB9A axis to function as a tumor inhibitor in melanoma.

Background: Isoliquiritigenin (ISL) presents antitumor effects against melanoma cells. It is known that various circular RNAs (circRNAs) are involved in the development of melanoma. Therefore, the present study aims to investigate the molecular mechanisms of ISL and circ_0002860. Methods: Circ_0002860, microRNA-431-5p (miR-431-5p) and member RAS oncogene family (RAB9A) were detected through reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assay. Cell viability was examined via cell counting kit-8 assay. The proliferation ability was assessed using colony formation assay. Cell apoptosis and cell cycle were determined by flow cytometry. Transwell assay was used for detection of migration and invasion. Western blot was conducted for protein analysis. Target binding was confirmed via dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. In vivo research was performed through xenograft tumor assay. Results: Circ_0002860 was downregulated by ISL in melanoma cells. ISL-induced inhibitory effects on cell proliferation, cell cycle progression, migration and invasion were alleviated by circ_0002860 overexpression. MiR-431-5p was a target of circ_0002860. Circ_0002860 eliminated the ISL-induced tumor inhibition via sponging miR-431-5p in melanoma cells. Circ_0002860 elevated the RAB9A level by targeting miR-431-5p. The function of ISL was related to miR-431-5p/RAB9A axis in melanoma progression. Tumor growth was reduced by ISL in vivo through downregulating circ_0002860 to regulate miR-431-5p and RAB9A levels. Conclusion: The current data indicates that ISL suppressed cell malignant progression of melanoma via targeting the circ_0002860/miR-431-5p/RAB9A pathway.

Downregulation of circ_0024028 inhibits IL-22-induced keratinocyte proliferation and migration by miR-486-3p/AKT3 axis.

Circular RNA (circRNA) has been confirmed to participate in psoriasis process, but the role of circ_0024028 in psoriasis development is still unclear. Interleukin 22 (IL-22)-induced keratinocytes (HaCaT) were used to construct psoriasis cell models in vitro. The expression of circ_0024028, microRNA (miR)-486-3p and AKT serine/threonine kinase 3 (AKT3) was analyzed by quantitative real-time PCR. Cell function was assessed by cell counting kit 8 assay, EdU assay, transwell assay, and wound healing assay. Protein expression was examined using western blot analysis. RNA interaction was confirmed by dual-luciferase reporter assay and RIP assay. Exosomes were isolated from cell culture medium using ultracentrifugation and examined by transmission electron microscopy and nanoparticle tracking analysis. Circ_0024028 was highly expressed in psoriasis lesions and IL-22-induced HaCaT cells, and its silencing could inhibit IL-22-induced HaCaT cell proliferation and migration. MiR-486-3p could be sponged by circ_0024028, and its inhibitor restored the functions of circ_0024028 knockdown on IL-22-induced HaCaT cell proliferation and migration. AKT3 was targeted by miR-486-3p, and its overexpression reversed the inhibitory effect of miR-486-3p on IL-22-induced HaCaT cell proliferation and migration. AKT3 expression was positively regulated by circ_0024028, and circ_0024028/miR-486-3p/AKT3 axis could regulate the activity of AKT/mTOR pathway. Additionally, exosomes mediated the transfer of circ_0024028 in cells. Circ_0024028 might be a potential target for psoriasis treatment, which knockdown repressed IL-22-induced keratinocytes proliferation and migration through miR-486-3p/AKT3 pathway.

Using "Age and Total-PSA" as the Main Indicators: The Results of Taizhou Integrated Prostate Screening (No 2).

The aim of the study was to analyze population-based prostate cancer (PCa) screening and the incidence of PCa among males ≥50 years of age residing in the Luqiao district of Taizhou, China. From October to December 2020, male residents ≥50 years of age were screened for serum total prostate-specific antigen (total-PSA). If t-PSA re-test levels persisted above 4 µg/L, subjects underwent further noninvasive examinations, including digital rectal examination or multiparameter magnetic resonance imaging (mpMRI) of the prostate. Subjects underwent prostate biopsy of pathological tissue based on t-PSA and mpMRI results. A total of 3524 (49.1%) residents participated in this PCa screening study. In total, 285 (8.1%) subjects exhibited t-PSA levels ≥4.0 µg/L and 112 (3.2%) underwent noninvasive examinations. Forty-two (1.2%) residents underwent prostate biopsy, of which 16 (0.45%) were diagnosed with PCa. Of those diagnosed with PCa, three (19%) had localized PCa (cT1-cT2N0M0), six (37%) had locally advanced PCa (cT3a- cT4N0-1M0), and seven (44%) had advanced metastatic PCa (M1). Unfortunately, 3477 (48.5%) residents did not participate in the study, mainly due to lack of awareness of PCa based on feedback from local health centers. Age and t-PSA were used as primary screening indicators and, when further combined with mpMRI and prostate biopsy, confirmed the diagnosis of PCa among participating residents. Although this was a relatively economical and convenient screening method, education and knowledge should be further enhanced to increase the participation rate in PCa screening programs.

A method for reducing thermal injury during the ureteroscopic holmium laser lithotripsy.

Objective: Many studies have demonstrated the heat effect from the holmium laser lithotripsy can cause persistent thermal injury to the ureter. The purpose of this study was to elucidate the use of a modified ureteral catheter with appropriate firing and irrigation to reduce the thermal injury to the "ureter" during the ureteroscopic holmium laser lithotripsy in vitro. Methods: An in vitro lithotripsy was performed using a modified catheter (5 Fr) as the entrance for the irrigation and the holmium laser fiber while using the remaining space in the ureteroscopic channel as an outlet. Different laser power settings (10 W, 20 W, and 30 W) with various firing times (3 s, 5 s, and 10 s) and rates of irrigation (15 mL/min, 20 mL/min, and 30 mL/min) were applied in the experiment. Temperature changes in the "ureter" were recorded with a thermometer during and after the lithotripsy. Results: During the lithotripsy, the local highest mean temperature was 60.3 °C and the lowest mean temperature was 26.7 °C. When the power was set to 10 w, the temperature was maintained below 43 °C regardless of laser firing time or irrigation flow. Regardless of the power or firing time selected, the temperature was below 43 °C at the rate of 30 mL/min. There was a significant difference in temperature decrease when continuous 3 s drainage after continuous firing (3 s, 5 s, or 10 s) compared to with not drainage (p<0.05) except for two conditions of 0.5 J×20 Hz, 30 mL/min, firing 5 s, and 1.0 J×10 Hz, 30 mL/min, firing 5 s. Conclusion: Our modified catheter with timely drainage reducing hot irrigation may significantly reduce the local thermal injury effect, especially along with the special interrupted-time firing setting during the simulated holmium laser procedure.

The impact of the COVID-19 pandemic on undergraduate and postgraduate students: A cross-sectional survey.

Background: The COVID-19 pandemic has impacted many facets of life. This study focuses on undergraduate and postgraduate students in China to explore how the pandemic has affected health status, daily life, learning situations, graduation-related situations, and their studies or work planning. Methods: This study sent online questionnaires to 2,395 participants to investigate the extent to which they were affected by the epidemic in the various aspects mentioned above and to understand what help they tend to get in the face of these effects. Results: A total of 2,000 valid questionnaires were collected. The physical health of 82.90% of the respondents was affected to varying degrees, with male students, non-medical students, and graduates being more affected than female students, students with medical majors, and non-graduates, respectively. The proportion of students affected by mental health, the total amount of physical exercise, emotional life, and interpersonal communication was 86.35, 88.65, 80.15, and 90.15%, respectively. Compared with medical students and non-graduates, non-medical students and graduates were more affected. In addition, students' learning and graduation conditions have also been affected to a certain extent: 13.07% of students may not be able to graduate on time, and the proportion of postgraduate students' graduations affected was higher than that of undergraduate students. Conclusion: The COVID-19 pandemic has affected the health status of students, their daily lives, learning situations, and so on to varying degrees. We need to pay attention to the issues, provide practical solutions, and provide a basis for better responses to similar epidemics in the future.

Crosstalk between G-quadruplex and ROS.

The excessive production of reactive oxygen species (ROS) can lead to single nucleic acid base damage, DNA strand breakage, inter- and intra-strand cross-linking of nucleic acids, and protein-DNA cross-linking involved in the pathogenesis of cancer, neurodegenerative diseases, and aging. G-quadruplex (G4) is a stacked nucleic acid structure that is ubiquitous across regulatory regions of multiple genes. Abnormal formation and destruction of G4s due to multiple factors, including cations, helicases, transcription factors (TFs), G4-binding proteins, and epigenetic modifications, affect gene replication, transcription, translation, and epigenetic regulation. Due to the lower redox potential of G-rich sequences and unique structural characteristics, G4s are highly susceptible to oxidative damage. Additionally, the formation, stability, and biological regulatory role of G4s are affected by ROS. G4s are involved in regulating gene transcription, translation, and telomere length maintenance, and are therefore key players in age-related degeneration. Furthermore, G4s also mediate the antioxidant process by forming stress granules and activating Nrf2, which is suggestive of their involvement in developing ROS-related diseases. In this review, we have summarized the crosstalk between ROS and G4s, and the possible regulatory mechanisms through which G4s play roles in aging and age-related diseases.

Circ_0084043 promotes cell proliferation and glycolysis but blocks cell apoptosis in melanoma via circ_0084043-miR-31-KLF3 axis.

Melanoma is an aggressive malignant tumor. The crucial role of circular RNAs has been documented in many types of cancer, including melanoma. The objective of this study was to uncover the function of circ_0084043 in the biological process of melanoma and associated mechanism of action. The expression of circ_0084043, miR-31, and Krüppel-like factor 3 (KLF3) was determined by qRT-PCR. Cell proliferation and apoptosis were monitored by the MTT assay and flow cytometry assay, respectively. The progression of glycolysis was evaluated according to the levels of glucose consumption, lactate production, and ATP concentration using appropriate detection kits. The relationship between miR-31 and circ_0084043 or KLF3 was predicted by the bioinformatics tool and ascertained by the dual-luciferase reporter assay. The protein levels of KLF3 and glucose transporter 1 (Glut1) were quantified by western blot. A xenograft model was established to ascertain the role of circ_0084043 in vivo. As a result, circ_0084043 expression was reinforced in melanoma tissues and cells. Circ_0084043 knockdown inhibited cell proliferation, induced cell apoptosis, and restrained glycolysis. MiR-31 was a target of circ_0084043, and miR-31 deficiency reversed the role of circ_0084043 knockdown. KLF3 was targeted by miR-31, and KLF3 upregulation abolished the effects of miR-31 enrichment. Moreover, circ_0084043 knockdown impeded tumor growth in vivo and suppressed the level of Glut1 by modulating miR-31 and KLF3. Circ_0084043 promoted cell proliferation and glycolysis, and blocked apoptosis through the circ_0084043-miR-31-KLF3 regulatory axis in melanoma.

Chelerythrine induced cell death through ROS-dependent ER stress in human prostate cancer cells.

INTRODUCTION: Prostate cancer is the most common noncutaneous cancer and the second leading cause of cancer-related mortality worldwide and the third in USA in 2017. Chelerythrine (CHE), a naturalbenzo[c]phenanthridine alkaloid, formerly identified as a protein kinase C inhibitor, has also shown anticancer effect through a number of mechanisms. Herein, effect and mechanism of the CHE-induced apoptosis via reactive oxygen species (ROS)-mediated endoplasmic reticulum (ER) stress in prostate cancer cells were studied for the first time. METHODS: In our present study, we investigated whether CHE induced cell viability decrease, colony formation inhibition, and apoptosis in a dose-dependent manner in PC-3 cells. In addition, we showed that CHE increases intracellular ROS and leads to ROS-dependent ER stress and cell apoptosis. RESULTS: Pre-treatment with N-acetyl cysteine, an ROS scavenger, totally reversed the CHE-induced cancer cell apoptosis as well as ER stress activation, suggesting that the ROS generation was responsible for the anticancer effects of CHE. CONCLUSION: Taken together, our findings support one of the anticancer mechanisms by which CHE increased ROS accumulation in prostate cancer cells, thereby leading to ER stress and caused intrinsic apoptotic signaling. The study reveals that CHE could be a potential candidate for application in the treatment of prostate cancer.

[A comparative study of nephrectomy and radical nephrectomy for renal cell carcinoma].

OBJECTIVE: To compare the clinical efficacy and safety of nephrectomy versus radical nephrectomy for renal cell carcinoma (RCC). METHODS: A total of 134 patients with renal carcinoma without metastasis in lymphatic system and distant sites were recruited. In random, 69 cases of renal cell carcinoma were elected for nephrectomy and the others radical nephrectomy. The operating time, blood loss, fasting time, postoperative hospital stay, information of tumor recurrence and metastasis, survival time without tumor, survival rate and perioperative complication were compared between two groups. RESULTS: In cases of nephrectomy, the operating time ranged from 60 - 135 minutes and blood loss 70 - 100 ml. In 4 cases, membrana pleuro-peritonealis was damaged. The fasting time ranged from 6 - 24 hours and postoperative hospital stay 5 - 8 days; the staging of all 69 cases was detected; follow-up studies ranged from 5 - 15 years, finding 1 case tumor metastasis in adrenal body and 1 case recurrent tumor in cases of radical nephrectomy, operating time ranged from 105 - 185 minutes and blood loss 150 - 2000 ml. Membrana pleuro-peritonealis was breached in 3 cases. The fasting time ranged from 12 - 90 hours and postoperative hospital stay 8 - 12 days. The staging of all 65 cases was detected. Follow-up studies of 5 - 15 years revealed 1 case of tumor metastasis in brain and 1 case of recurrent tumor. There was no significant difference in perioperative complication, tumor recurrence, tumor metastasis and survival time without tumor between those two groups (P > 0.05). The blood loss, operating time, fasting and postoperative hospital stay were less than that in radical nephrectomy group (P < 0.05). CONCLUSION: In patients without metastasis in lymphatic system and distant sites, nephrectomy is both effective and safe. It has the advantages of a short operating time, a short postoperative hospital stay and less damage and blood loss than radical nephrectomy.

[Preventive strategies and causes of common complications of ureteroscopy].

OBJECTIVE: To discuss the causes of common complications of ureteroscopy and how to prevent them. METHODS: A total of 768 cases of common complications of ureteroscopy were retrospectively analyzed from February 2004 to February 2009. RESULTS: The intra-operative complications were failed entry (n = 6, 0.78%), ureterostoma injury and ureterostoma submucosa pseudocana (n = 12, 1.56%), ureteral perforation (n = 16, 2.08%), stone displacement (n = 13, 1.87%) and ureteral mucosa evulsion (n = 3, 0.39%). And the post-operative complications were lumbago or renal colic (n = 11, 1.43%), infection (n = 9, 1.17%)and severe hematuria (n = 5, 0.65%). CONCLUSION: Skillful operative techniques and strict indications are key to reducing complications of ureteroscopy.