Differential expression and prognostic value of TLR4 in kidney renal clear cell carcinoma.

Human Toll-like receptor (TLR) family plays a crucial role in immunity and cancer progression. However, the specific role of human Toll-like receptor 4 (TLR4) in kidney renal clear cell carcinoma (KIRC) remains obscure. Thus, we used single-cell RNA sequencing (RNA-seq) and bulk RNA-seq data combined with in vitro studies to evaluate the expression and prognostic value of TLR4 in KIRC. In our study, we observed that TLR4 was over expressed in KIRC tissues compared to normal renal tissues. And the expression of TLR4 was higher in macrophages/monocytes than other cell types. Besides, there is a close association between TLR4 expression and immune cell infiltration (Neutrophils, Macrophages, T cells and B cells) in KIRC. Immunohistochemical staining also showed that TLR4 was overexpressed in inflammatory infiltration renal tissue compared with normal tissue. Meanwhile, high expression of TLR4 exhibited correlations with improved survival, lower tumor grade and stage. Interestingly, the protective significance of TLR4 only showed in female patients (HR = 0.37, P < 0.01), other than male patients (HR = 0.71, P = 0.08) with KIRC. Consistently, KIRC samples with lymph node metastasis showed lower expression of TLR4. Knockdown of TLR4 in 786-O cell line increased cell proliferation and clonogenic capacity. In summary, this study found TLR4 could inhibit the progression of kidney cancer and was associated with improved survival in KIRC. The overexpression of TLR4 in macrophages and the close association between TLR4 and immune cell infiltration also underline the critical role of TLR4 in building the immune microenvironment for kidney cancer. These results may offer insights into the mechanism and immune microenvironment of kidney cancer.

[Value of cardiodynamicsgram in early diagnosis of patients with acute coronary syndrome].

OBJECTIVE: To explore the value of cardiodynamicsgram (CDG) obtained from electrocardiogram (ECG) data by radial basis functionradial basis function (RBF) neural network in early diagnosis of patients with acute coronary syndrome (ACS). METHODS: Retrospective analysis method was used. Patients with chest pain as the main initial symptom in the emergency department of Baoan District People's Hospital of Shenzhen from October 2021 to September 2022 were enrolled. Baseline data were collected, including gender, age, smoking history, family history of coronary heart disease and history of hypertension, diabetes, hyperlipidemia, and atherosclerosis. The first 12-lead ECG was recorded after admission to the emergency department, and electrocardiodynamics analysis was performed to generate CDG. Receiver operator characteristic curve (ROC curve) was plotted to analyze the value of CDG and ECG in the early diagnosis of ACS and non-ST segment elevation ACS (NSTE-ACS). Sensitivity, specificity, area under the ROC curve (AUC), and 95% confidence interval (95%CI) were calculated. CDG and coronary angiography results of 3 patients with ACS with normal ECG were observed and analyzed. Non-ACS patients with normal ECG but positive CDG were followed for 30 days for adverse cardiovascular events. RESULTS: A total of 384 patients with chest pain were included, including 169 patients with ACS and 215 patients without ACS. The proportion of male (87.0% vs. 53.0%), smoking history (37.9% vs. 12.1%), hypertension (46.2% vs. 22.3%), diabetes (24.3% vs. 7.9%), hyperlipidemia (55.0% vs. 14.0%) and history of atherosclerosis (22.5% vs. 2.3%) in ACS group were significantly higher than those in non-ACS group (all P < 0.05). The ROC curve showed that the AUC of CDG diagnosis of ACS was higher than that of ECG [AUC (95%CI): 0.88 (0.66-0.76) vs. 0.71 (0.84-0.92)], the sensitivity was 92.8%, 78.6%, and the specificity was 83.3%, 64.2%, respectively. The AUC of CDG diagnosis of NSTE-ACS was higher than that of ECG [AUC (95%CI): 0.85 (0.80-0.90) vs. 0.63 (0.56-0.69)], the sensitivity was 87.1%, 61.3%, and the specificity was 83.3%, 64.2%, respectively. CDG of 3 patients with ACS with normal ECG showed disordered state, and coronary angiography showed ≥70% stenosis of major coronary branches. Of 215 non-ACS patients, 20 had a normal ECG but positive CDG, and 3 developed ST segment elevation myocardial infarction (STEMI) within 30 days, and 2 developed unstable angina (UA) within 30 days. CONCLUSIONS: CDG has high value in early diagnosis of ACS patients and is expected to become an important means of early diagnosis of ACS in emergency.

CYLD regulates cell ferroptosis through Hippo/YAP signaling in prostate cancer progression.

Prostate cancer (PCa) is one of the most common malignancy in men. However, the molecular mechanism of its pathogenesis has not yet been elucidated. In this study, we demonstrated that CYLD, a novel deubiquitinating enzyme, impeded PCa development and progression via tumor suppression. First, we found that CYLD was downregulated in PCa tissues, and its expression was inversely correlated with pathological grade and clinical stage. Moreover, we discovered that CYLD inhibited tumor cell proliferation and enhanced the sensitivity to cell ferroptosis in PCa in vitro and in vivo, respectively. Mechanistically, we demonstrated that CYLD suppressed the ubiquitination of YAP protein, then promoted ACSL4 and TFRC mRNA transcription. Then, we demonstrated that CYLD could enhance the sensitivity of PCa xenografts to ferroptosis in vivo. Furthermore, we discovered for the first time that there was a positive correlation between CYLD expression and ACSL4 or TFRC expression in human PCa specimens. The results of this study suggested that CYLD acted as a tumor suppressor gene in PCa and promoted cell ferroptosis through Hippo/YAP signaling.

Cancer-associated fibroblasts in neoadjuvant setting for solid cancers.

Therapeutic approaches for cancer have become increasingly diverse in recent times. A comprehensive understanding of the tumor microenvironment (TME) holds great potential for enhancing the precision of tumor therapies. Neoadjuvant therapy offers the possibility of alleviating patient symptoms and improving overall quality of life. Additionally, it may facilitate the reduction of inoperable tumors and prevent potential preoperative micrometastases. Within the TME, cancer-associated fibroblasts (CAFs) play a prominent role as they generate various elements that contribute to tumor progression. Particularly, extracellular matrix (ECM) produced by CAFs prevents immune cell infiltration into the TME, hampers drug penetration, and diminishes therapeutic efficacy. Therefore, this review provides a summary of the heterogeneity and interactions of CAFs within the TME, with a specific focus on the influence of neoadjuvant therapy on the microenvironment, particularly CAFs. Finally, we propose several potential and promising therapeutic strategies targeting CAFs, which may efficiently eliminate CAFs to decrease stroma density and impair their functions.

MYO5A overexpression promotes invasion and correlates with low lymphocyte infiltration in head and neck squamous carcinoma.

Head and neck squamous carcinoma (HNSC) poses a significant public health challenge due to its substantial morbidity. Nevertheless, despite advances in current treatments, the prognosis for HNSC remains unsatisfactory. To address this, single-cell RNA sequencing (RNA-seq) and bulk RNA-seq data combined with in vitro studies were conducted to examine the role of MYO5A (Myosin VA) in HNSC. Our investigation revealed an overexpression of MYO5A in HNSC that promotes HNSC migration in vitro. Remarkably, knockdown of MYO5A suppressed vimentin expression. Furthermore, analyzing the TCGA database evidenced that MYO5A is a risk factor for human papillomavirus positive (HPV+) HNSC (HR = 0.81, P < 0.001). In high MYO5A expression HNSC, there was a low count of tumor infiltrating lymphocytes (TIL), including activated CD4+ T cells, CD8+ T cells, and B cells. Of note, CD4+ T cells and B cells were positively associated with improved HPV+ HNSC outcomes. Correlation analysis demonstrated a decreased level of immunostimulators in high MYO5A-expressing HNSC. Collectively, these findings suggest that MYO5A may promote HNSC migration through vimentin and involve itself in the process of immune infiltration in HNSC, advancing the understanding of the mechanisms and treatment of HNSC.

Effects of intermittent theta-burst transcranial magnetic stimulation on post-traumatic stress disorder symptoms: A randomized controlled trial.

Post-traumatic stress disorder (PTSD) is a prevalent and debilitating illness, which can be alleviated by transcranial magnetic stimulation (TMS). Intermittent theta burst stimulation (iTBS), a newer form of repetitive transcranial magnetic stimulation (rTMS), offers the advantage of shorter treatment sessions compared to the standard 10 Hz rTMS treatment. In order to compare the two forms of TMS, we enrolled 75 participants aged between 18 and 55 years who presented with (PCL-C) scale score of at least 50. Participants were randomly assigned to groups in a ratio of 1:1:1, receiving either 10 Hz rTMS, iTBS, or sham-controlled iTBS. Participants in the two treatment groups underwent 15 therapies which consisted of 1800 pulses and targeted the right dorsolateral prefrontal cortex (DLPFC). The main outcomes included changes in scores on the PCL-C and the Post-Traumatic Growth Inventory (PTGI). After intervention, the PCL-C and PTGI scores in iTBS and rTMS groups were significantly different from those in sham-controlled iTBS group. No significant differences in PCL-C and PTGI were found between the two active treatment groups. ITBS, with a shorter treatment duration, can effectively improve the symptoms of PTSD, with no significant difference in effect from that of rTMS. Future studies need to further elucidate the mechanisms, optimize the parameters and investigate the therapeutic potential and efficacy of iTBS in PTSD.

Consensus on the pharmacological treatment of acute stress disorder in Chinese pilots: a Delphi study.

BACKGROUND: Appropriate medication is very important for pilots with acute stress disorder. Improper medication can not only affect the physical and mental health of the pilots but can also endanger flight safety. Hence, we aimed to quickly and effectively relieve symptoms and restore cognitive function by forming a consensus of Chinese experts on the pharmacological treatment of acute stress disorder in pilots using the Delphi method. METHODS: Relevant literature was searched to enumerate the current status of pharmacological treatment of acute stress disorder in pilots, followed by two rounds of expert consultation and discussion according to the listed status of the survey using the Delphi method. A descriptive statistical method was used to analyze the basic information, authority coefficients, concentration of opinions, and survey items of the experts to develop a consensus on the pharmacological treatment of acute stress disorder in pilots. RESULTS: A total of 16 experts in psychiatry, pharmacology, and aerospace medicine from different provinces and cities across China were invited for consultation. The recovery rate of the two rounds of consultation was 100%, and the expert authority coefficients were 0.897 and 0.906, respectively. Kendall's coefficient of concordance of indicators at all levels was 0.564-0.594 (p < 0.01). Based on the number of votes received, alprazolam tablets (16), eszopiclone tablets (15), and lorazepam tablets (14) were recommended for the treatment of excitatory psychomotor symptoms of acute stress disorder; paroxetine tablets (15) and sertraline tablets (15) were available for psychomotor depressive symptoms; olanzapine tablets (15), olanzapine orally disintegrating tablets (14), and quetiapine fumarate tablets (14) were selected for psychotic symptoms. CONCLUSIONS: This study formed a consensus on rapid and effective pharmacological treatment for different symptoms of acute stress disorder pilots, which provides a reference for clinical treatment.

Predictive factors associated with differential pathologic response to neoadjuvant chemohormonal therapy in high-risk localized prostate cancer.

PURPOSE: To explore the clinical parameters and molecular biomarkers that can predict differential pathologic response to neoadjuvant chemohormonal therapy (NCHT) in prostate cancer (CaP). METHODS: A total of 128 patients with primary high-risk localized CaP who had received NCHT followed by radical prostatectomy (RP) were included. Androgen receptor (AR), AR splice variant-7 (AR-V7) and Ki-67 staining were evaluated in prostate biopsy specimens by immunohistochemistry. The pathologic response to NCHT in whole mount RP specimens was measured based on the reduction degree of tumor volume and cellularity compared to the paired pretreatment needle biopsy, and divided into 5 tier grades (Grades 0-4). Patients with Grades 2 to 4 (the reduction degree more than 30%) were defined as having a favorable response. Logistic regression was performed to explore the predictive factors associated with a favorable pathologic response. The predictive accuracy was evaluated by receiver operating characteristic (ROC) curve and area under the ROC curve (AUC). RESULTS: Ninety-seven patients (75.78%) had a favorable response to NCHT. Logistic regression showed that the preoperative PSA level, low AR expression and high Ki-67 expression in biopsy specimens were associated with a favorable pathologic response (P < 0.05). Furthermore, the AUC of the preoperative PSA level, AR and Ki-67 were 0.625, 0.624 and 0.723, respectively. Subgroup analysis revealed that the rate of favorable pathologic response to NCHT was 88.5% in patients with ARlowKi-67high, which was higher than patients with ARlowKi-67low, ARhighKi-67low, and ARhighKi-67high (88.5% vs. 73.9%, 72.9%, and 70.9%, all P < 0.05). CONCLUSIONS: A lower preoperative PSA level was an independent predictive factor for a favorable pathologic response. Moreover, the expression status of AR and Ki-67 in biopsy specimens were associated with differential pathologic response to NCHT, and AR low/Ki-67 high was also associated with favorable response but warrants further evaluation in this patient subgroup and future trial clinical trial design.

Biodegradable polycarbonates from lignocellulose based 4-pentenoic acid and carbon dioxide.

The production of biodegradable polycarbonate by copolymerizing CO2 with epoxides has emerged as an effective method to utilize CO2 in response to growing concerns about CO2 emissions and plastic pollution. Previous studies have mainly focused on the preparation of CO2-based polycarbonates from petrochemical-derived propylene oxide (PO) or cyclohexene oxide (CHO). However, to reduce dependence on fossil fuels, the development of 100% bio-based polymers has gained attention in polymer synthesis. Herein, we reported the synthesis of glycidyl 4-pentenoate (GPA) from lignocellulose based 4-pentenoic acid (4-PA), which was further copolymerized with CO2 using a binary catalyst SalenCoCl/PPNCl to produce bio-based polycarbonates with vinyl side chains and molecular weights up to 17.1 kg/mol. Introducing a third monomer, PO, allows for the synthesis of the GPA/PO/CO2 terpolymer, and the glass transition temperature (T g) of the terpolymer can be adjusted from 2°C to 19°C by controlling the molar feeding ratio of GPA to PO from 7:3 to 3:7. Additionally, post-modification of the vinyl side chains enables the production of functional polycarbonates, providing a novel approach to the preparation of bio-based materials with diverse side chains and functions.

Machine learning-based signature of necrosis-associated lncRNAs for prognostic and immunotherapy response prediction in cutaneous melanoma and tumor immune landscape characterization.

Background: Cutaneous melanoma (CM) is one of the malignant tumors with a relative high lethality. Necroptosis is a novel programmed cell death that participates in anti-tumor immunity and tumor prognosis. Necroptosis has been found to play an important role in tumors like CM. However, the necroptosis-associated lncRNAs' potential prognostic value in CM has not been identified. Methods: The RNA sequencing data collected from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression Project (GTEx) was utilized to identify differentially expressed genes in CM. By using the univariate Cox regression analysis and machine learning LASSO algorithm, a prognostic risk model had been built depending on 5 necroptosis-associated lncRNAs and was verified by internal validation. The performance of this prognostic model was assessed by the receiver operating characteristic curves. A nomogram was constructed and verified by calibration. Furthermore, we also performed sub-group K-M analysis to explore the 5 lncRNAs' expression in different clinical stages. Function enrichment had been analyzed by GSEA and ssGSEA. In addition, qRT-PCR was performed to verify the five lncRNAs' expression level in CM cell line (A2058 and A375) and normal keratinocyte cell line (HaCaT). Results: We constructed a prognostic model based on five necroptosis-associated lncRNAs (AC245041.1, LINC00665, AC018553.1, LINC01871, and AC107464.3) and divided patients into high-risk group and low-risk group depending on risk scores. A predictive nomogram had been built to be a prognostic indicator to clinical factors. Functional enrichment analysis showed that immune functions had more relationship and immune checkpoints were more activated in low-risk group than that in high-risk group. Thus, the low-risk group would have a more sensitive response to immunotherapy. Conclusion: This risk score signature could be used to divide CM patients into low- and high-risk groups, and facilitate treatment strategy decision making that immunotherapy is more suitable for those in low-risk group, providing a new sight for CM prognostic evaluation.

The value of anti-rods and rings antibodies in Chinese population of Dalian City: A retrospective study.

The study aimed to investigate the clinical significance of anti-rods and rings (anti-RR) antibodies in antinuclear antibodies (ANAs) test samples retrospectively. The laboratory data and clinical details of patients with positive anti-RR antibodies were collected and analysed between December 2017 and May 2022 in the First Affiliated Hospital of Dalian Medical University. A total of 72 665 patients were tested for ANAs. There were 45 632 patients discovered with positive ANAs (62.80%), only 131 patients presented with anti-RR antibodies (0.18%), among which only 68 patients were hospitalized patients with a definitive diagnosis. Among the 68 patients with a definitive diagnosis, 8 of 68 (11.8%) had autoimmune diseases, and 19 of 68 (27.9%) had renal diseases. Other diseases included liver disease, pulmonary disease, cerebral ischemia, cerebral infarction, chronic cardiac failure and venous thromboembolism. The detection rate of high titre(≥1:1000) anti-RR antibodies is significantly higher in autoimmune diseases.

Sparse angle CT reconstruction based on group sparse representation.

OBJECTIVE: In order to solve the problem of image quality degradation of CT reconstruction under sparse angle projection, we propose to develop and test a new sparse angle CT reconstruction method based on group sparse. METHODS: In this method, the group-based sparse representation is introduced into the statistical iterative reconstruction framework as a regularization term to construct the objective function. The group-based sparse representation no longer takes a single patch as the minimum unit of sparse representation, while it uses Euclidean distance as a similarity measure, thus it divides similar patch into groups as basic units for sparse representation. This method fully considers the local sparsity and non-local self-similarity of image. The proposed method is compared with several commonly used CT image reconstruction methods including FBP, SART, SART-TV and GSR-SART with experiments carried out on Sheep_Logan phantom and abdominal and pelvic images. RESULTS: In three experiments, the visual effect of the proposed method is the best. Under 64 projection angles, the lowest RMSE is 0.004776 and the highest VIF is 0.948724. FSIM and SSIM are all higher than 0.98. Under 50 projection angles, the index of the proposed method remains achieving the best image quality. CONCLUSION: Qualitative and quantitative results of this study demonstrate that this new proposed method can not only remove strip artifacts, but also effectively protect image details.

RASAL2 regulates the cell cycle and cyclin D1 expression through PI3K/AKT signalling in prostate tumorigenesis.

Prostate cancer (PCa) growth and progression are uniquely dependent on androgens, making the androgen receptor pathway a prime target for therapy; however, cancer progression to androgen independence leads to treatment failure and poor prognosis. In recent years, alternative therapeutic pathways for PCa have been extensively explored, such as the PTEN/PI3K/AKT pathway, cell cycle, and DNA repair. In the present study, we discovered that RASAL2, a RAS-GTPase-activating protein, acted as an oncogene to regulate cancer cell proliferation and the cell cycle and contributed to tumorigenesis via the PI3K/AKT/cyclin D1 pathway. First, RASAL2 expression was higher in PCa tumour and metastatic lymph node tissues than in matched adjacent nontumor tissues and was associated with higher PCa tumour stage, Gleason score and poorer prognosis. Mechanistically, we found that RASAL2 promoted tumour cell proliferation, the transition from G1 to S phase in vitro and tumour growth in vivo. Furthermore, we demonstrated that RASAL2 facilitated phosphorylation of AKT, which in turn increased the expression of cyclin D1 encoded by the CCND1 gene. In addition, there was a positive correlation between the expression of RASAL2 and cyclin D1 in subcutaneous xenografts and clinical specimens. Taken together, these findings indicate that RASAL2 plays an oncogenic role in prostate cancer and may promote PCa tumorigenesis through PI3K/AKT signalling and cyclin D1 expression.

Dynamic changes in heparin-binding protein as a prognostic biomarker for 30-day mortality in sepsis patients in the intensive care unit.

Heparin-binding protein (HBP) has been shown to be a robust predictor of the progression to organ dysfunction from sepsis, and we hypothesized that dynamic changes in HBP may reflect the severity of sepsis. We therefore aim to investigate the predictive value of baseline HBP, 24-h, and 48-h HBP change for prediction of 30-day mortality in adult patients with sepsis. This is a prospective observational study in an intensive care unit of a tertiary center. Patients aged 20 years or older who met SEPSIS-3 criteria were prospectively enrolled from August 2019 to January 2020. Plasma levels of HBP were measured at admission, 24 h, and 48 h and dynamic changes in HBP were calculated. The Primary endpoint was 30-day mortality. We tested whether the biomarkers could enhance the predictive accuracy of a multivariable predictive model. A total of 206 patients were included in the final analysis. 48-h HBP change (HBPc-48 h) had greater predictive accuracy of area under the curve (AUC: 0.82), followed by baseline HBP (0.79), PCT (0.72), lactate (0.71), and CRP (0.65), and HBPc-24 h (0.62). Incorporation of HBPc-48 h into a clinical prediction model significantly improved the AUC from 0.85 to 0.93. HBPc-48 h may assist clinicians with clinical outcome prediction in critically ill patients with sepsis and can improve the performance of a prediction model including age, SOFA score and Charlson comorbidity index.

Efficacy and Prognosis of Hyperbaric Oxygen as Adjuvant Therapy for Neonatal Hypoxic-Ischemic Encephalopathy: A Meta-Analysis Study.

Background: Preclinical and clinical evidence suggests that hyperbaric oxygen therapy (HBOT) may benefit newborns. The effectiveness of HBOT for neonatal hypoxic-ischemic encephalopathy (HIE) remains controversial. We conducted a meta-analysis to evaluate the efficacy and prognosis of HBOT in neonates with HIE. Methods: A systematic search of eight databases was performed for available articles published between January 1, 2015, and September 30, 2020, to identify randomized controlled clinical trials (RCTs) on HBOT for neonatal HIE. Methodological quality assessment was performed by applying the simple procedure detailed by the Cochrane collaboration. Afterward, quality assessment and data analysis were performed using Revman 5.3 software. STATA 15 software was used to detect publication bias as well as for sensitivity analysis. Results: A total of 46 clinical RCTs were selected for the study and included 4,199 patients with neonatal HIE. The results indicated that HBOT significantly improved the total efficiency (TEF) of treatment for neonatal HIE patients [odds ratio (OR) = 4.61, 95% confidence interval (CI) (3.70, 5.75), P < 0.00001] and reduced the risk of sequelae (OR = 0.23, 95% CI (0.16, 0.33), P < 0.00001) and the neonatal behavioral neurological assessment (NBNA) scores [mean difference (MD) = 4.51, 95%CI (3.83,5.19, P < 0.00001)]. Conclusion: In light of the effectiveness of HBOT neonatal HIE, this meta-analysis suggested that HBOT can be a potential therapy for the treatment of neonatal HIE. Due to the heterogeneity of studies protocol and patient selection being only from China, more research is needed before this therapy can be widely implemented in the clinic. Protocol Registration: PROSPERO (ID: CRD42020210639). Available online at: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020210639.

The Incidence and Characteristics of Perinatal Stroke in Beijing: A Multicenter Study.

Objective: To assess the incidence, risk factors, and clinical characteristics of perinatal stroke in Beijing. Methods: This multicenter prospective study included all the live births from 17 representative maternal delivery hospitals in Beijing from March 1, 2019 to February 29, 2020. Neonates with a stroke were assigned to the study group. Clinical data, including general information, clinical manifestations, and risk factors, were collected. Up until 18 months after birth, neonates were routinely assessed according to the Ages and Stages Questionnaire (ASQ) and/or the Bayley scale. Statistical analysis was done using the chi-squared, t-tests, and logistic regression analysis using SPSS version 26.0. Outcomes: In total, 27 cases were identified and the incidence of perinatal stroke in Beijing was 1/2,660 live births, including 1/5,985 for ischemic stroke and 1/4,788 for hemorrhagic stroke. Seventeen cases (62.96%) of acute symptomatic stroke and convulsions within 72 h (10 cases, 37.04%) were the most common presentations. Ten patients showed no neurological symptoms and were found to have had a stroke through routine cranial ultrasonography after being hospitalized for non-neurological diseases. The risk factors include primiparity, placental or uterine abruption/acute chorioamnionitis, intrauterine distress, asphyxia, and severe infection. In the study group, 11.1% (3/27) of patients had adverse neurodevelopmental outcomes. The patients in the study group had lower scores for the ASQ than those in the control group in the communication, gross, and fine motor dimensions. Conclusion: The incidence of perinatal stroke in Beijing was consistent with that in other countries. Routine neuroimaging of infants with risk factors may enable identification of asymptomatic strokes in more patients. Patients who have suffered from a stroke may have neurological sequelae; therefore, early detection, treatment, and regular follow-ups are beneficial for improving their recovery outcomes.

DAB2IP regulates intratumoral testosterone synthesis and CRPC tumor growth by ETS1/AKR1C3 signaling.

The intratumoral androgen synthesis is one of the mechanisms by which androgen receptor (AR) is aberrantly re-activated in castration-resistant prostate cancer (CRPC) after androgen ablation. However, pathways controlling steroidogenic enzyme expression and de novo androgen synthesis in prostate cancer (PCa) cells are largely unknown. In this study, we explored the potential roles of DAB2IP in testosterone synthesis and CRPC tumor growth. Indeed, DAB2IP loss could maintain AR transcriptional activity, PSA re-expression and tumor growth under castrated condition in vitro and in vivo, and reprogram the expression profiles of steroidogenic enzymes, including AKR1C3. Mechanistically, DAB2IP could dramatically inhibit the AKR1C3 promoter activity and the conversion from androgen precursors (i.e., DHEA) to testosterone through PI3K/AKT/mTOR/ETS1 signaling. Consistently, there was a high co-expression of ETS1 and AKR1C3 in PCa tissues and xenografts, and their expression in prostate tissues could also restore AR nuclear staining in castrated DAB2IP-/- mice after DHEA supplement. Together, this study reveals a novel regulation of intratumoral de novo androgen synthesis in CRPC, and provides the DAB2IP/ETS1/AKR1C3 signaling as a potential therapeutic target.

[Discussion on automated external defibrillator configuration optimization strategy of rapidly developing city: a case study of Bao'an, Shenzhen].

OBJECTIVE: To explore the automated external defibrillator (AED) configuration optimization strategy in line with the characteristics of the rapidly developing cities by analyzing the actual coverage of AED in Bao'an District based on the real world data of out-of-hospital cardiac arrest (OHCA) in Bao'an District, Shenzhen City. METHODS: The data of cardiac arrest database registered in Bao'an District of Shenzhen City from March 1, 2019 to February 29, 2020 were included in a retrospective observational study. The AED coverage of public and non-public areas was analyzed by calculating the minimum distance between the occurrence place of each OHCA event and the nearest AED. The minimum distance ≤ 100 m was set as AED coverage, and the minimum distance > 100 m was set as non-AED coverage. It was assumed that one AED was configured for each OHCA hotspot area, then the AED coverage changes were analyzed. Based on the actual situation that the AED in schools, governments, sports venues, subways, tourist attractions and parks of public areas in Bao'an District could not be obtained at any time within 24 hours, it was assumed that all AED in the public areas could be obtained at any time within 24 hours, the impact of AED available at any time on AED coverage was analyzed. RESULTS: A total of 525 cases of OHCA were enrolled. The highest incidence of OHCA was found in residential and industrial areas [54.5% (286/525) and 14.3% (75/525), respectively]. There were 252 AED in Bao'an District, Shenzhen, and 115 OHCA events occurred within the coverage area of AED. Even if all AED met the ideal state that could be obtained at any time within 24 hours, the coverage rate was only 21.9% (115/525). The AED coverage rate of the public areas and non-public areas was 31.6% (37/117) and 19.1% (78/408) respectively, with uneven distribution, and the AED coverage rate of non-public areas was low. Assuming that the residential community and industrial zone with more than 2 OHCA cases were respectively equipped with one AED, the coverage rate of AED in the non-public areas increased from 19.1% (78/408) to 28.2% (115/408), basically meeting the requirement that AED could be obtained at any time when OHCA events occurred. Some AED in the public areas of Bao'an District were not available at any time within 24 hours. If the ideal state that all AED in the public area could be obtained at any time within 24 hours could be achieved, the AED coverage rate of all regions increased from 16.8% (88/525) to 21.9% (115/525), the AED coverage rate of the public areas increased from 29.1% (34/117) to 31.6% (37/117), the AED coverage rate of the non-public areas increased from 13.2% (54/408) to 19.1% (78/408). CONCLUSIONS: AED configuration in Bao'an District was unevenly distributed, and the coverage rate of AED in non-public areas was low. The allocation strategy for AED in fast-growing cities like Shenzhen should be as follows: on the premise of ensuring AED availability for 24 hours, priority should be given to covering the number of AED in the non-public areas including residential communities and industrial zones; AED is available in the public areas for 24 hours.

Sidechain Metallopolymers with Precisely Controlled Structures: Synthesis and Application in Catalysis.

Inspired by the cooperative multi-metallic activation in metalloenzyme catalysis, artificial enzymes as multi-metallic catalysts have been developed for improved kinetics and higher selectivity. Previous models about multi-metallic catalysts, such as cross-linked polymer-supported catalysts, failed to precisely control the number and location of their active sites, leading to low activity and selectivity. In recent years, metallopolymers with metals in the sidechain, also named as sidechain metallopolymers (SMPs), have attracted much attention because of their combination of the catalytic, magnetic, and electronic properties of metals with desirable mechanical and processing properties of polymeric backbones. Living and controlled polymerization techniques provide access to SMPs with precisely controlled structures, for example, controlled degree of polymerization (DP) and molecular weight dispersity (D), which may have excellent performance as multi-metallic catalysts in a variety of catalytic reactions. This review will cover the recent advances about SMPs, especially on their synthesis and application in catalysis. These tailor-made SMPs with metallic catalytic centers can precisely control the number and location of their active sites, exhibiting high catalytic efficiency.