DEAD-box helicase 1 inhibited CD8+ T cell antitumor activity by inducing PD-L1 expression in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) does not respond well to current treatments, even immune checkpoint inhibitors. PD-L1 (programmed cell death ligand 1 or CD274 molecule)-mediated immune escape of tumor cells may be a key factor affecting the efficacy of immune checkpoint inhibitor (ICI) therapy. However, the regulatory mechanisms of PD-L1 expression and immune escape require further exploration. Here, we observed that DDX1 (DEAD-box helicase 1) was overexpressed in HCC tissues and associated with poor prognosis in patients with HCC. Additionally, DDX1 expression correlated negatively with CD8+ T cell frequency. DDX1 overexpression significantly increased interferon gamma (IFN-γ)-mediated PD-L1 expression in HCC cell lines. DDX1 overexpression decreased IFN-γ and granzyme B production in CD8+ T cells and inhibited CD8+ T cell cytotoxic function in vitro and in vivo. In conclusion, DDX1 plays an essential role in developing the immune escape microenvironment, rendering it a potential predictor of ICI therapy efficacy in HCC.

Discovery of first-in-class highly selective TRPV1 antagonists with dual analgesic and hypoglycemic effects.

Analgesia and blood sugar control are considered as two main unmet clinical needs for diabetes related neuropathic pain patients. Transient receptor potential vanilloid type-1 (TRPV1) channel is a highly validated target for pain perception, while no TRPV1 antagonists have been approved due to hyperthermia side effects. Herein, two series of new TRPV1 antagonists with flavonoid skeleton were designed by the structure-based drug design (SBDD) strategy. After comprehensive evaluation, compound CX-3 was identified as a promising TRPV1 antagonist. CX-3 exhibited equivalent TRPV1 antagonistic activity with classical TRPV1 antagonist BCTC in vitro, and exerted better analgesic activity in vivo than that of BCTC in the formalin induced inflammatory pain model without hyperthermia risk. Moreover, CX-3 exhibited robust glucose-lowering effects and showed high selectivity over other ion channels. Overall, these findings identified a first-in-class highly selective TRPV1 antagonist CX-3, which is a promising candidate to target the pathogenesis of diabetes related neuropathic pain.

Discovery of LH10, a novel fexaramine-based FXR agonist for the treatment of liver disease.

Farnesoid X receptor (FXR) was considered as a promising drug target in the treatment of cholestasis, drug-induced liver injury, and non-alcoholic steatohepatitis (NASH). However, the existing FXR agonists have shown different degrees of side effects in clinical trials without clear interpretation. MET-409 in clinical phase Ⅲ, has been proven significantly fewer side effects than that of other FXR agonists. This may be due to the completely different structure of FEX and other non-steroidal FXR agonists. Herein, the structure-based drug design was carried out based on FEX, and the more active FXR agonist LH10 (FEX EC50 = 0,3 µM; LH10 EC50 = 0.14 µM)) was screened out by the comprehensive SAR studies. Furthermore, LH10 exhibited robust hepatoprotective activity on the ANIT-induced cholestatic model and APAP-induced acute liver injury model, which was even better than positive control OCA. In the nonalcoholic steatohepatitis (NASH) model, LH10 significantly improved the pathological characteristics of NASH by regulating several major pathways including lipid metabolism, inflammation, oxidative stress, and fibrosis. With the above attractive results, LH10 is worthy of further evaluation as a novel agent for the treatment of liver disorders.

Design, synthesis, and biological evaluation studies of novel carboxylesterase 2 inhibitors for the treatment of irinotecan-induced delayed diarrhea.

Human carboxylesterase 2 (hCES2A), one of the most important serine hydrolases distributed in the small intestine and colon, plays a crucial role in the hydrolysis of various prodrugs and esters. Accumulating evidence has demonstrated that the inhibition of hCES2A effectively alleviate the side effects induced by some hCES2A-substrate drugs, including delayed diarrhea caused by the anticancer drug irinotecan. Nonetheless, there is a scarcity of selective and effective inhibitors that are suitable for irinotecan-induced delayed diarrhea. Following screening of the in-house library, the lead compound 01 was identified with potent inhibition on hCES2A, which was further optimized to obtain LK-44 with potent inhibitory activity (IC50 = 5.02 ± 0.67 µM) and high selectivity on hCES2A. Molecular docking and molecular dynamics simulations indicated that LK-44 can formed stable hydrogen bonds with amino acids surrounding the active cavity of hCES2A. The results of inhibition kinetics studies unveiled that LK-44 inhibited hCES2A-mediated FD hydrolysis in a mixed inhibition manner, with a Ki value of 5.28 µM. Notably, LK-44 exhibited low toxicity towards HepG2 cells according to the MTT assay. Importantly, in vivo studies showed that LK-44 significantly reduced the side effects of irinotecan-induced diarrhea. These findings suggested that LK-44 is a potent inhibitor of hCES2A with high selectivity against hCES1A, which has potential as a lead compound for the development of more effective hCES2A inhibitors to mitigate irinotecan-induced delayed diarrhea.

Flap perfusion assessment with indocyanine green angiography in deep inferior epigastric perforator flap breast reconstruction: A systematic review and meta-analysis.

BACKGROUND: Indocyanine green angiography (ICG-A) has been widely applied for intraoperative flap assessment in DIEP flap breast reconstruction. However, the beneficial effect of ICG-A in DIEP flap breast reconstruction is still uncertain and no standardized protocol is available. This study aims to analyze the clinical outcome and comprehensively review protocols of this field. METHODS: A systematic review was conducted in MEDLINE, EMBASE, and Cochrane CENTRAL databases until September 15, 2022. Studies on the utility of intraoperative ICG-A in DIEP breast reconstruction were included. Data reporting reconstruction outcomes were extracted for pooled analysis. RESULTS: A total of 22 studies were enrolled in the review, among five studies with 1021 patients included in the meta-analysis. The protocols of ICG-A assessment of DIEP flap varied among studies. According to the pooled results, the incidence of postoperative fat necrosis was 10.89% (50 of 459 patients) with ICG-A and 21.53% (121 of 562 patients) with clinical judgment. The risk for postoperative fat necrosis was significantly lower in patients with intraoperative ICG-A than without (RR 0.47 95% CI 0.29-0.78, p = .004, I2 = 51%). Reoperation occurred in 5 of 48 patients (10.42%) in the ICG-A group and in 21 of 64 patients (32.82%) in the control group summarized from reports in two studies. The risk for reoperation was lower in the ICG-A group than in the control group (RR 0.41 95% CI 0.18-0.93, p = .03, I2 = 0%). Other complications, including flap loss, seroma, hematoma, dehiscence, mastectomy skin necrosis, and infection, were comparable between the two groups. Heterogeneities among studies were acceptable. No significant influence of specific studies was identified in sensitivity analysis. CONCLUSIONS: ICG-A is an accurate and reliable way to identify problematic perfusion of DIEP flaps during breast reconstruction. Protocols of ICG-A differed in current studies. Intraoperative ICG-A significantly decreases the rate of fat necrosis and reoperation in patients undergoing DIEP breast reconstruction. The synthesized results should be interpreted sensibly due to the sample size limitation. RCTs on the outcomes and high-quality studies for an optimized ICG-A protocol are still needed in the future.

Blood pressure control and renal function preservation of ex vivo renal artery repair with orthotopic renal autotransplantation for complex renal artery diseases.

OBJECTIVE: To assess the outcome of ex vivo renal artery repair with orthotopic renal autotransplantation for patients with complex renal artery disease. METHODS: The single-center study collected and analyzed the data from patients with complex renal artery disease undergoing ex vivo renal artery repair with orthotopic renal autotransplantation, retrospectively. RESULTS: A total of 21 complex renal artery lesions from 19 patients were included. The mean blood pressure showed a significant decrease from the preoperative to the postoperative period (P < .05). Renal function kept stable for the perioperative period. No significant serum creatinine and estimated glomerular filtration rate alteration was observed compared with the immediate postoperative period (P = .439 and .904, respectively). The median renal cold ischemia time was 35.5 (76) minutes. Two patients developed perioperative complications, one with acute cholecystitis and one with acute renal failure after graft occlusion in a solitary kidney. During the median follow-up of 48 months, one single bypass graft of a solitary kidney was occluded, and four grafts developed restenosis. The primary and primary-assisted patency rates at the 5-year follow-up were 81.3% and 87.5%, respectively. No deaths were observed in the follow-up period. CONCLUSIONS: Ex vivo renal artery reconstruction with orthotopic renal autotransplantation in patients with complex renal artery disease offers stable control of blood pressure and renal function preservation, and should be considered as a potential alternative for other open surgical procedures.

Design, synthesis, and biological studies of dual URAT1 inhibitor and FXR agonist based on benzbromarone.

With increased unhealthy dietary patterns and a sedentary lifestyle, the prevalence of hyperuricemia is growing rapidly, placing a tremendous burden on the public health system. Persistent hyperuricemia in extreme cases induces gout, gouty arthritis, and other metabolic diseases. Benzbromarone is a potent human urate transporter 1 (URAT1) inhibitor that is widely used as a uric acid-lowering drug. Recent studies indicated that benzbromarone can also activate farnesoid X receptor (FXR), whereas its agonistic activity on FXR is rather poor. Mounting evidence suggested that the etiology of gout is directly related to NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasomes, and FXR suppresses the expression of NLRP3 in various ways. Therefore, the dual URAT1 inhibitor and FXR agonist may exert synergistic effects on decreasing uric acid (UA) levels and inhibiting inflammation. To obtain a better dual URAT1 inhibitor and FXR agonist, we performed the structure-based drug design (SBDD) strategy to improve the FXR activation of benzbromarone by forming strong interactions with ARG331 in FXR binding pocket. All of these efforts lead to the identification of compound 4, which exerts better activity on FXR and uric acid-lowering effect than benzbromarone.

Design, synthesis and biological evaluation studies of novel anti-fibrosis agents bearing sulfoxide moiety.

Fibrosis, a chronic disease with high morbidity and mortality, is mainly characterized by excessive accumulation of extracellular matrix (ECM). At present, pathogenesis of fibrosis is incompletely understood, and there is an urgent need to develop safe and effective drugs. In this study, we designed and synthesized a series of novel small-molecule compounds through structural modification and fragment hybridization. Among them, a potential anti-fibrosis drug compd.1 was founded to be able to dose-dependently down-regulate ACTA2 and CTGF mRNA levels in human hepatic stellate cells (LX-2) treated with TGF-ß. In addition, compd.1 significantly improved the bridging fibrosis and collagen content in the CCl4-induced liver fibrosis mice model. Moreover, compd.1 reduced lung inflammation and fibrotic area in bleomycin-induced pulmonary fibrosis mice model. These findings suggested that compd.1 is a promising candidate for further anti-fibrosis researches, and extended chemical space might help us to explore better anti-fibrosis drug.

Extraventricular site indicates higher grade but better prognosis in adult supratentorial ependymomas: a 14-year single-center retrospective cohort.

Supratentorial extraventricular ependymoma (STEE) and supratentorial intraventricular ependymoma (STIE) are two subsets of supratentorial ependymoma (SE). These two subsets have similar gene features and only differ in original sites: STEE occurs in the brain parenchyma, and STIE is located in ventricles and surrounded by cerebral spinal fluid. The present study aims to depict the diversities of these two subsets and elucidate the potential effects of the anatomic site on the tumor with the same type, grade, and molecular features. Sixty-six consecutive adult SE patients from 2008 to 2021 were enrolled in our study. Clinical data, pathological features, and long-term outcomes were analyzed retrospectively. Results demonstrated that adult STEE presented with a higher proportion of WHO grade 3 (P = .028) and higher Ki-67 index (≥10%) (P = .019) compared to adult STIE. Survival analysis demonstrated that patients of grade 3 STEE exhibited a significantly longer overall survival (OS) than patients of grade 3 STIE (median OS, 24.4 months vs. 13.0 months; P = .004). Grade 2 (hazard ratio (HR) = 0.217; P < .001) and gross total resection (GTR) (HR = 0.156; P < .001) were identified as favorable prognostic factors for all adult SE. The STEE was also associated with a lesser hazard of death for patients of grade 3 on multivariate analysis (HR = 0.263; P = .047). These findings suggested that the extraventricular site was an indicator for higher grade and better prognosis in adult supratentorial ependymoma.

Bone marrow infiltrated natural killer cells predicted the anti-leukemia activity of MCL1 or BCL2 inhibitors in acute myeloid leukemia.

Acute myeloid leukemia (AML) is still incurable due to its heterogeneity and complexity of tumor microenvironment. It is imperative therefore to understand the molecular pathogenesis of AML and identify leukemia-associated biomarkers to formulate effective treatment strategies. Here, we systematically analyzed the clinical characters and natural killer (NK) cells portion in seventy newly-diagnosis (ND) AML patients. We found that the proportion of NK cells in the bone marrow of ND-AML patients could predict the prognosis of patients by analyzing the types and expression abundance of NK related ligands in tumor cells. Furthermore, MCL1 inhibitor but not BCL2 inhibitor combined with NK cell-based immunotherapy could effectively improve the therapeutic efficiency via inhibiting proliferation and inducing apoptosis of AML primary cells as well as cell lines in vitro. There results provide valuable insights that could help for exploring new therapeutic strategies for leukemia treatment.

[Differences of Gut Microbiota Diversity between Patients with Abdominal Aortic Aneurysm and Atherosclerosis].

Objective To investigate the differences of gut microbiota between patients with abdominal aortic aneurysm and atherosclerosis.Methods From December 2018 to June 2019,20 fresh stool samples were collected respectively from the patients with abdominal aortic aneurysm and atherosclerosis treated at the Department of Vascular Surgery,Peking Union Medical College Hospital.The 16S rDNA high-throughput sequencing was employed to compare the composition,abundance,and α and ß diversities of gut microbiota between the two disease groups,and further determine the significantly differential genera.Results The two groups had great similarities in the composition of gut microbiota.There was no statistical difference in α diversity.Although ß diversity did not have statistically significant difference,certain microbial taxa showed differences between the two groups.The LEfSe demonstrated that the abdominal aortic aneurysm group had higher relative abundance of Leuconostocaceae,Ruminococcaceae,Weissella,and Faecalibacterium while lower relative abundance of Firmicuteria,Selenomonadales,and Veillonellaceae.Conclusion The structure of gut microbiota has differences between patients with abdominal aortic aneurysm and atherosclerosis,and sample size should be enlarged to validate the results.

Identification of a metabolic gene panel to predict the prognosis of myelodysplastic syndrome.

Myelodysplastic syndrome (MDS) is clonal disease featured by ineffective haematopoiesis and potential progression into acute myeloid leukaemia (AML). At present, the risk stratification and prognosis of MDS need to be further optimized. A prognostic model was constructed by the least absolute shrinkage and selection operator (LASSO) regression analysis for MDS patients based on the identified metabolic gene panel in training cohort, followed by external validation in an independent cohort. The patients with lower risk had better prognosis than patients with higher risk. The constructed model was verified as an independent prognostic factor for MDS patients with hazard ratios of 3.721 (1.814-7.630) and 2.047 (1.013-4.138) in the training cohort and validation cohort, respectively. The AUC of 3-year overall survival was 0.846 and 0.743 in the training cohort and validation cohort, respectively. The high-risk score was significantly related to other clinical prognostic characteristics, including higher bone marrow blast cells and lower absolute neutrophil count. Moreover, gene set enrichment analyses (GSEA) showed several significantly enriched pathways, with potential indication of the pathogenesis. In this study, we identified a novel stable metabolic panel, which might not only reveal the dysregulated metabolic microenvironment, but can be used to predict the prognosis of MDS.

Prognostic significance of autophagy-related genes within esophageal carcinoma.

BACKGROUND: Several works suggest the importance of autophagy during esophageal carcinoma development. The aim of the study is to construct a scoring system according to the expression profiles of major autophagy-related genes (ARGs) among esophageal carcinoma cases. METHODS: The Cancer Genome Atlas was employed to obtain the esophageal carcinoma data. Thereafter, the online database Oncolnc ( http://www.oncolnc.org/ ) was employed to verify the accuracy of our results. According to our results, the included ARGs were related to overall survival (OS). RESULTS: We detected the expression patterns of ARG within esophageal carcinoma and normal esophageal tissues. In addition, we identified the autophagy related gene set, including 14 genes displaying remarkable significance in predicting the esophageal carcinoma prognosis. The cox regression results showed that, 7 ARGs (including TBK1, ATG5, HSP90AB1, VAMP7, DNAJB1, GABARAPL2, and MAP2K7) were screened to calculate the ARGs scores. Typically, patients with higher ARGs scores were associated with poorer OS. Moreover, the receiver operating characteristic (ROC) curve analysis suggested that, ARGs accurately distinguished the healthy people from esophageal carcinoma patients, with the area under curve (AUC) value of > 0.6. CONCLUSION: A scoring system is constructed in this study based on the main ARGs, which accurately predicts the outcomes for esophageal carcinoma.

Identification of potential proteases for abdominal aortic aneurysm by weighted gene coexpression network analysis.

Proteases are involved in the degradation of the extracellular matrix (ECM), which contributes to the formation of abdominal aortic aneurysm (AAA). To identify new disease targets in addition to the results of previous microarray studies, we performed next-generation sequencing (NGS) of the whole transcriptome of Angiotensin II-treated ApoE-/- male mice (n = 4) and control mice (n = 4) to obtain differentially expressed genes (DEGs). Identified DEGs of proteases were analyzed using weighted gene coexpression network analysis (WGCNA). RT-qPCR was conducted to validate the differential expression of selected hub genes. We found that 43 DEGs were correlated with the expression of the protease profile, and most were clustered in immune response module. Among 26 hub genes, we found that Mmp16 and Mmp17 were significantly downregulated in AAA mice, while Ctsa, Ctsc, and Ctsw were upregulated. Our functional annotation analysis of genes coexpressed with the five hub genes indicated that Ctsw and Mmp17 were involved in T cell regulation and Cell adhesion molecule pathway, respectively, and that both were involved in general regulation of the cell cycle and gene expression. Overall, our data suggest that these ectopic genes are potentially crucial to AAA formation and may act as biomarkers for the diagnosis of AAA.

Crucial Gene Identification in Carotid Atherosclerosis Based on Peripheral Blood Mononuclear Cell (PBMC) Data by Weighted (Gene) Correlation Network Analysis (WGCNA).

BACKGROUND Many patients are not responsive or tolerant to medical therapies for carotid atherosclerosis. Thus, elucidating the molecular mechanism for the pathogenesis and progression of carotid atherosclerosis and identifying new potential molecular targets for medical therapies that can slow progression of carotid atherosclerosis and prevent ischemic events are quite important. MATERIAL AND METHODS We downloaded the expression profiling data of PBMC in Biobank of Karolinska Endarterectomy (BiKE, GSE21545) for GEO. The WGCNA and DEG screening were conducted. The co-expression pattern between patients with ischemic events (the events group) and patients without ischemic events (the no-events group) were compared. Then, we identified hub genes of each module. Finally, the DEG co-expression network was constructed and MCODE was used to identify crucial genes based on this co-expression network. RESULTS In the study, 183 DEGs were screened and 8 and 6 modules were assessed in the events group and no-events group, respectively. Compared to the no-events group, genes associated with inflammation and immune response were clustered in the green-yellow module of the events group. The hub gene of the green-yellow module of the events group was KIR2DL5A. We obtained 1 DEG co-expression network, which has 16 nodes and 24 edges, and we detected 5 crucial genes: SIRT1, THRAP3, RBM43, PEX1, and KLHDC2. The upregulated genes (THRAP3 and RBM43) showed potential diagnostic and prognostic value for the occurrence of ischemic events. CONCLUSIONS We detected 8 modules for the events group and 6 modules for the no-events group. The hub genes for modules and crucial genes of the DEG co-expression network were also identified. These genes might serve as potential targets for medical therapies and biomarkers for diagnosis and prognosis. Further experimental and biological studies are needed to elucidate the role of these crucial genes in the progression of carotid atherosclerosis.

Community-based rehabilitation service in Chengdu, Southwest China: a cross-sectional general survey.

BACKGROUND: World Health Organization initiated community-based rehabilitation (CBR) in 1978, and by now, it has been an essential process of medical services worldwide. China had strengthened primary health care on building more than 35,000 community health centers (CHCs) in cities, and more than 34,000 township health centers (THCs) in the rural area. Nevertheless, it remains unclear that if these primary health centers could provide optional rehabilitation services for disabilities. And this study aims at evaluating the supply capacity of rehabilitation service in primary health centers of Chengdu, a regional center city of southwest China. METHOD: We conducted a general investigation of primary health centers in Chengdu, a city located in southwest China with more than 15 million population. Our investigation covered all of Chengdu's 390 primary health centers from October to November 2016. We researched these primary health centers on basic rehabilitation services, diseases, and rehabilitation equipment quantity and quality, and traditional Chinese medicine (TCM) physiotherapy. RESULT: Rehabilitation therapy is available in 88.9% (337 of 379) of all primary health centers. Meanwhile, CHCs slightly surpass THCs with an available rate of 92.2% (106 of 115) and 87.5% (231 of 264), respectively. Traditional Chinese Medicine (TCM) physiotherapy is available in 97.1% (368 of 379) of all primary health centers, 97.3% (112 of 115) of CHCs and 97.0% (256 of 264) of THCs. Quantitative analysis showed that substantial factors which could make an impact on the number of patients per year contain: categories of rehabilitation disease (P < 0.001, 95% confidence interval (CI) [- 1.571, - 0.702]),number of rehabilitation bed (P < 0.001, 95%CI [- 1.249, - 0.290]). CONCLUSION: CBR and TCM physiotherapy has become accessible for disabilities in most basic health centers of Chengdu City, whereas, available rate of CBR in THCs is lesser than in CHCs, which suggests an imbalance in primary health service development between rural and urban area. Categories of rehabilitation diseases, and the number of rehabilitation beds constitute co-factors that make an impact on the CBR capacity of basic health centers.

Chromobox homolog 8 is a predictor of muscle invasive bladder cancer and promotes cell proliferation by repressing the p53 pathway.

Chromobox homolog 8 (CBX8), also known as human polycomb 8, is a repressor that maintains the transcriptionally repressive state in various cellular genes, and has been reported to promote tumorigenesis. In the present study, we examined CBX8 expression in eight pairs of muscle invasive bladder cancer tissues and adjacent non-tumor tissues, and found that CBX8 was frequently upregulated in muscle invasive bladder cancer tissues when compared to adjacent non-tumor tissues. Analysis showed that high expression of CBX8 in 152 muscle invasive bladder cancer specimens was associated with progression of the T, N, and M stages (P = 0.004, 0.005, <0.001, respectively). Furthermore, Kaplan-Meier survival analysis and log-rank test showed that muscle invasive bladder cancer patients with high CBX8 expression had a poor rate of overall survival (P < 0.001) and 5-year recurrence-free survival (P < 0.001) compared to patients with low CBX8 expression. High CBX8 expression predicted poor overall survival and 5-year recurrence-free survival in T and N stages of muscle invasive bladder cancer patients. Moreover, knockdown of CBX8 inhibited cell proliferation of urothelial carcinoma of the bladder both in vitro and in vivo. In addition, CBX8 depletion resulted in cell cycle delay of urothelial carcinoma cells of the bladder at the G2/M phase by the p53 pathway. The data suggest that high expression of CBX8 plays a critical oncogenic role in aggressiveness of urothelial carcinoma cells of the bladder through promoting cancer cell proliferation by repressing the p53 pathway, and CBX8 could be used as a novel predictor for muscle invasive bladder cancer patients.

Recent Advances on Small-Molecule Inhibitors of Lipocalin-like Proteins.

Lipid transfer proteins (LTPs) are crucial players in nonvesicular lipid trafficking. LTPs sharing a lipocalin lipid transfer domain (lipocalin-like proteins) have a wide range of biological functions, such as regulating immune responses and cell proliferation, differentiation, and death as well as participating in the pathogenesis of inflammatory, metabolic, and neurological disorders and cancer. Therefore, the development of small-molecule inhibitors targeting these LTPs is important and has potential clinical applications. Herein, we summarize the structure and function of lipocalin-like proteins, mainly including retinol-binding proteins, lipocalins, and fatty acid-binding proteins and discuss the recent advances on small-molecule inhibitors for these protein families and their applications in disease treatment. The findings of our Perspective can provide guidance for the development of inhibitors of these LTPs and highlight the challenges that might be faced during the procedures.

Roles of Wettability and Wickability on Enhanced Hydrogen Evolution Reactions.

Bubble dynamics significantly impact mass transfer and energy conversion in electrochemical gas evolution reactions. Micro-/nanostructured surfaces with extreme wettability have been employed as gas-evolving electrodes to promote bubble departure and decrease the bubble-induced overpotential. However, effects of the electrodes' wickability on the electrochemical reaction performances remain elusive. In this work, hydrogen evolution reaction (HER) performances are experimentally investigated using micropillar array electrodes with varying interpillar spacings, and effects of the electrodes' wettability, wickability as well as bubble adhesion are discussed. A deep learning-based object detection model was used to obtain bubble counts and bubble departure size distributions. We show that microstructures on the electrode have little effect on the total bubble counts and bubble size distribution characteristics at low current densities. At high current densities, however, micropillar array electrodes have much higher total bubble counts and smaller bubble departure sizes compared with the flat electrode. We also demonstrate that surface wettability is a critical factor influencing HER performances under low current densities, where bubbles exist in an isolated regime. Under high current densities, where bubbles are in an interacting regime, the wickability of the micropillar array electrodes emerges as a determining factor. This work elucidates the roles of surface wettability and wickability on enhancing electrochemical performances, providing guidelines for the optimal design of micro-/nanostructured electrodes in various gas evolution reactions.