O-GlcNAcylation promotes tumor immune evasion by inhibiting PD-L1 lysosomal degradation.

Programmed-death ligand 1 (PD-L1) and its receptor programmed cell death 1 (PD-1) mediate T cell-dependent immunity against tumors. The abundance of cell surface PD-L1 is a key determinant of the efficacy of immune checkpoint blockade therapy targeting PD-L1. However, the regulation of cell surface PD-L1 is still poorly understood. Here, we show that lysosomal degradation of PD-L1 is regulated by O-linked N-acetylglucosamine (O-GlcNAc) during the intracellular trafficking pathway. O-GlcNAc modifies the hepatocyte growth factor-regulated tyrosine kinase substrate (HGS), a key component of the endosomal sorting machinery, and subsequently inhibits its interaction with intracellular PD-L1, leading to impaired lysosomal degradation of PD-L1. O-GlcNAc inhibition activates T cell-mediated antitumor immunity in vitro and in immune-competent mice in a manner dependent on HGS glycosylation. Combination of O-GlcNAc inhibition with PD-L1 antibody synergistically promotes antitumor immune response. We also designed a competitive peptide inhibitor of HGS glycosylation that decreases PD-L1 expression and enhances T cell-mediated immunity against tumor cells. Collectively, our study reveals a link between O-GlcNAc and tumor immune evasion, and suggests strategies for improving PD-L1-mediated immune checkpoint blockade therapy.

O-GlcNAcylation regulates epidermal growth factor receptor intracellular trafficking and signaling.

SignificanceEpidermal growth factor receptor (EGFR) is one of the most important membrane receptors that transduce growth signals into cells to sustain cell growth, proliferation, and survival. EGFR signal termination is initiated by EGFR internalization, followed by trafficking through endosomes, and degradation in lysosomes. How this process is regulated is still poorly understood. Here, we show that hepatocyte growth factor regulated tyrosine kinase substrate (HGS), a key protein in the EGFR trafficking pathway, is dynamically modified by a single sugar N-acetylglucosamine. This modification inhibits EGFR trafficking from endosomes to lysosomes, leading to the accumulation of EGFR and prolonged signaling. This study provides an important insight into diseases with aberrant growth factor signaling, such as cancer, obesity, and diabetes.

Sialic Acid-Modified O-GlcNAc Transferase Inhibitor Liposome Presents Antitumor Effect in Hepatocellular Carcinoma.

O-linked-N-acetylglucosaminylation (O-GlcNAcylation) plays a key role in hepatocellular carcinoma (HCC) development, and the inhibition of O-GlcNAcylation has therapeutic potential. To decrease the systemic adverse events and increase targeting, we used sialic acid (SA)-decorated liposomes loaded with OSMI-1, an inhibitor of the O-GlcNAcylation, to further improve the anti-HCC effect. Fifty pairs of HCC tissue samples and the cancer genome atlas database were used to analyze the expression of O-GlcNAc transferase (OGT) and its effects on prognosis and immune cell infiltration. OSMI-1 cells were treated with SA and liposomes. Western blotting, immunofluorescence, cell proliferation assay, flow cytometry, enzyme-linked immunosorbent assay, immunohistochemistry, and tumorigenicity assays were used to investigate the antitumor effect of SA-modified OSMI-1 liposomes in vitro and in vivo. OGT was highly expressed in HCC tissues, negatively correlated with the degree of tumor infiltration of CD8+ and CD4+T cells and prognosis, and positively correlated with the degree of Treg cell infiltration. SA-modified OSMI-1 liposome (OSMI-1-SAL) was synthesized with stable hydrodynamic size distribution. Both in vitro and in vivo, OSMI-1-SAL exhibited satisfactory biosafety and rapid uptake by HCC cells. Compared to free OSMI-1, OSMI-1-SAL had a stronger capacity for suppressing the proliferation and promoting the apoptosis of HCC cells. Moreover, OSMI-1-SAL effectively inhibited tumor initiation and development in mice. OSMI-1-SAL also promoted the release of damage-associated molecular patterns, including anticalreticulin, high-mobility-group protein B1, and adenosine triphosphate, from HCC cells and further promoted the activation and proliferation of the CD8+ and CD4+T cells. In conclusion, the OSMI-1-SAL synthesized in this study can target HCC cells, inhibit tumor proliferation, induce tumor immunogenic cell death, enhance tumor immunogenicity, and promote antitumor immune responses, which has the potential for clinical application in the future.

Association of PM2.5 exposure in early pregnancy and maternal liver function: A retrospective cohort study in Shenzhen, China.

OBJECTIVE: Studies have shown that fine particulate matter (PM2.5) has adverse effects on the liver function, but epidemiological evidence is limited, especially regarding pregnant women. This study aims to investigate the association between PM2.5 exposure in early pregnancy and maternal liver function during pregnancy. METHODS: This retrospective cohort study included 13,342 pregnant participants. PM2.5 and Ozone (O3) exposure level, mean temperature, and relative humidity for each participant were assessed according to their residential address. The levels of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin (TBIL) were measured during the second and third trimesters. Data on PM2.5 and O3 exposure level were sourced from Tracking Air Pollution in China (TAP), while the mean temperature and relative humidity were obtained from the ERA5 dataset. The Generalized Additive Model (GAM) was used to analyze the associations between PM2.5 exposure and maternal liver function during pregnancy, adjusting for potential confounding factors. RESULTS: According to the results, each 10 µg/m3 increase in PM2.5 was associated with an increase of 3.57% (95% CI: 0.29%, 6.96%) in ALT and 4.25% (95% CI: 2.33%, 6.21%) in TBIL during the second trimester and 4.51% (95% CI: 2.59%, 6.47%) in TBIL during the third trimester., respectively. After adjusting for O3, these associations remained significant, and the effect of PM2.5 on ALT during the second trimester was further strengthened. No significant association observed between PM2.5 and AST. CONCLUSIONS: PM2.5 exposure in early pregnancy is associated with increasement of maternal ALT and TBIL, suggesting that PM2.5 exposure may have an adverse effect on maternal liver function. Although this finding indicates an association between PM2.5 exposure and maternal liver function, more research is needed to confirm our findings and explore the underlying biological mechanisms.

Ochratoxin A detoxification potentials of basil, chan, and chia seeds.

The most toxic of the ochratoxins is ochratoxin A (OTA), which is primarily produced by species of Aspergillus and Penicillium that can be found in maize, wheat, coffee, red wine, and various grains. OTA induces immunotoxicity, nephrotoxicity, hepatotoxicity, teratogenicity, and carcinogenicity in both animals and humans. Thus, there is a need to identify mycotoxin detoxification agents that can effectively decontaminate OTA. Seeds of basil (Ocimum basilicum L.), chan (Hyptis suaveolens L.), and chia (Salvia hispanica L.) are functional foods capable of eliminating harmful substances. Despite this potential, the impact of these seeds on OTA detoxification remains unclear. This study reveals that milled basil, chan, and chia seeds adsorb significant levels of OTA, with chia demonstrating the highest adsorption capacity, followed by chan and basil seeds showing the least efficiency. Furthermore, milled basil, chan, and chia seeds effectively reduced OTA residues in artificial gastric and intestinal fluids, where they achieved up to 93% OTA adsorption in the former. In addition, these milled seeds were able to remove OTAs from canned, drip, and instant coffee. This study is the first to report the OTA elimination potential of basil, chan, and chia seeds.

SNHG16 promotes hepatocellular carcinoma development via activating ECM receptor interaction pathway.

BACKGROUND: Accumulating data have suggested that long non-coding RNAs (lncRNAs) play important roles in regulating tumor cell growth. This study was designed to investigate the role of SNHG16 in hepatocellular carcinoma (HCC). METHODS: SNHG16 expression was detected with real-time polymerase chain reaction (PCR). The cutoff value of SNHG16 for tumor-free survival (TFS) was determined with receiver operating characteristic curve analysis. Small interfering RNA was used to inhibit the expression of SNHG16 in HCC cell lines. The biologic behavior of HCC cell was determined with cell viability assay and Transwell assay in vitro. The potential predictive value of SNHG16 on prognosis was analyzed by Kaplan-Meier curves and Cox proportional hazards regression model. RESULTS: SNHG16 expression was upregulated in tumor tissues and HCC cell lines. High expression of SNHG16 was associated with tumor recurrence and poor prognosis after surgery. Multivariate analysis revealed that SNHG16 was an independent prognostic factor for poor recurrence-free survival. Moreover, inhibition of SNHG16 in HepG2, Hep3B, and BEL-7402 cells significantly reduced cell invasiveness and proliferation. Mechanistic analyses indicated that the ECM-receptor interaction pathway was remarkably activated by SNHG16. CONCLUSIONS: SNHG16 might be a promising biomarker for predicting tumor recurrence in HCC patients after surgery and a potential therapeutic target for HCC.

One-Step Enzymatic Labeling Reveals a Critical Role of O-GlcNAcylation in Cell-Cycle Progression and DNA Damage Response.

O-linked N-acetylglucosamine (O-GlcNAcylation) is a ubiquitous post-translational modification of proteins that is essential for cell function. Perturbation of O-GlcNAcylation leads to altered cell-cycle progression and DNA damage response. However, the underlying mechanisms are poorly understood. Here, we develop a highly sensitive one-step enzymatic strategy for capture and profiling O-GlcNAcylated proteins in cells. Using this strategy, we discover that flap endonuclease 1 (FEN1), an essential enzyme in DNA synthesis, is a novel substrate for O-GlcNAcylation. FEN1 O-GlcNAcylation is dynamically regulated during the cell cycle. O-GlcNAcylation at the serine 352 of FEN1 disrupts its interaction with Proliferating Cell Nuclear Antigen (PCNA) at the replication foci, and leads to altered cell cycle, defects in DNA replication, accumulation of DNA damage, and enhanced sensitivity to DNA damage agents. Thus, our study provides a sensitive method for profiling O-GlcNAcylated proteins, and reveals an unknown mechanism of O-GlcNAcylation in regulating cell cycle progression and DNA damage response.

Associations between obesity and metabolic health with nonalcoholic fatty liver disease in elderly Chinese.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is closely associated with obesity. However, this association could be influenced by the coexisting metabolic abnormalities. This study aimed to investigate the role of obesity and metabolic abnormalities in NAFLD among elderly Chinese. METHODS: A cross-sectional study was performed among elderly residents who took their annual health checkups during 2016 in Keqiao District, Shaoxing, China. RESULTS: A total of 3359 elderly adults were retrospectively included in this study. The overall prevalence of NAFLD was 28.7%. The prevalence of NAFLD were 7.14%, 27.92%, 34.80%, and 61.02% in participants with metabolically healthy normal weight (MHNW), metabolically abnormal normal weight (MANW), metabolically healthy obese (MHO), and metabolically abnormal obese (MAO), respectively. NAFLD patients in MHO group had more unfavorable metabolic profiles than those in MHNW group. Logistic regression analysis showed that sex, body mass index (BMI), fasting blood glucose, and serum uric acid were the risk factors of NAFLD. CONCLUSIONS: Both obesity and metabolic health were significantly associated with NAFLD in elderly Chinese. Screening for obesity and other metabolic abnormalities should be routinely performed for early risk stratification of NAFLD.

YAP promotes multi-drug resistance and inhibits autophagy-related cell death in hepatocellular carcinoma via the RAC1-ROS-mTOR pathway.

BACKGROUND: Multi-drug resistance is the major cause of chemotherapy failure in hepatocellular carcinoma (HCC). YAP, a critical effector of the Hippo pathway, has been shown to contribute to the progression, metastasis and invasion of cancers. However, the potential role of YAP in mediating drug resistance remains obscure. METHODS: RT-qPCR and western blot were used to assess YAP expression in HCC cell lines. CCK-8 assays, flow cytometry, a xenograft tumour model, immunochemistry and GFP-mRFP-LC3 fusion proteins were utilized to evaluate the effect of YAP on multi-drug resistance, intracellular ROS production and the autophagy of HCC cells in vitro and in vivo. Autophagy inhibitor and rescue experiments were carried out to elucidate the mechanism by which YAP promotes chemoresistance in HCC cells. RESULTS: We found that BEL/FU, a typical HCC cell line with chemoresistance, exhibited overexpression of YAP. Moreover, the inhibition of YAP by shRNA or verteporfin conferred the sensitivity of BEL/FU cells to chemotherapeutic agents through autophagy-related cell death in vitro and in vivo. Mechanistically, YAP silencing significantly enhanced autophagic flux by increasing RAC1-driven ROS, which contributed to the inactivation of mTOR in HCC cells. In addition, the antagonist of autophagy reversed the enhanced effect of YAP silencing on cell death under treatment with chemotherapeutic agents. CONCLUSION: Our findings suggested that YAP upregulation endowed HCC cells with multi-drug resistance via the RAC1-ROS-mTOR pathway, resulting in the repression of autophagy-related cell death. The blockade of YAP may serve as a promising novel therapeutic strategy for overcoming chemoresistance in HCC.

Lower mean platelet volume is a risk indicator of hepatocellular carcinoma recurrence following liver transplantation.

BACKGROUND: Lower mean platelet volume (MPV) is an indicator of platelet activity in the setting of tumor development. This study was to assess the relationship between preoperative MPV and survival outcomes of patients with hepatocellular carcinoma (HCC) following liver transplantation (LT). METHODS: The demographic and clinical characteristics of 304 HCC patients following LT were retrieved from an LT database. All the patients were divided into the normal and lower MPV groups according to the median MPV. The factors were first analyzed using a Kaplan-Meier survival analysis, then the factors with P < 0.10 were selected for multivariate Cox regression analysis and were used to define the independent risk factors for poor prognosis. RESULTS: The 1-, 3-, and 5-year tumor free survival was 95.34%, 74.67% and 69.29% in the normal MPV group, respectively, and 95.40%, 59.97% and 42.94% in the lower MPV group, respectively (P < 0.01). No significant difference was observed in post-LT complications between the normal and lower MPV groups. Portal vein tumor thrombosis (PVTT) [hazard ratio (HR = 2.24; 95% confidence interval: 1.46-3.43; P < 0.01) and lower MPV (HR = 1.58; 95% confidence interval: 1.05-2.36; P = 0.03) were identified as independent prognostic risk factors for recipient survival. CONCLUSION: Preoperative lower MPV is a risk indicator of HCC patients survival outcomes after LT.

A high frequency of CD8+CD28- T-suppressor cells contributes to maintaining stable graft function and reducing immunosuppressant dosage after liver transplantation.

CD8+CD28-T cells (CD8Ts) exert immunosuppressive effects in various autoimmune diseases. The current study was designed to investigate the role of defects in CD8Ts in liver transplantation (LT). The proportion of CD8Ts in peripheral blood was determined by flow cytometry. The mean proportion of CD8Ts was 23.39% in recipients with stable graft function and 16.64% in those with graft dysfunction following LT compared with 19.86% in the healthy cohort. After receiving enhanced immunosuppressive therapy, patients in the rejection group who achieved recovery of graft function showed an increase in the proportion of CD8Ts (from 17.39% to 25.55%), but those in the group with refractory graft dysfunction showed no significant change (12.49% to 10.30%). Furthermore, in the first year after LT, recipients longer removed in time from the LT date exhibited a higher proportion of CD8Ts. Patients benefited most from tacrolimus concentrations of 5-10 ng/ml in the first year after LT and 0-5 ng/ml thereafter. Moreover, the change in the proportion of CD8Ts (ΔCD8Ts) was significantly higher in recipients with stable graft function than in those with graft dysfunction. These results suggest that a high frequency of CD8Ts prevents rejection and contributes to reduce immunosuppressant dosage and even induces tolerance.

Lower tacrolimus trough levels in the late period after living donor liver transplantation contribute to improvements in long-term clinical outcomes.

BACKGROUND: Previous studies have emphasized the need to reduce tacrolimus (TAC) trough levels in the early post-liver transplantation (LT) period. However, whether late-period TAC trough levels influence the long-term outcomes of liver recipients is not clear. METHODS: We enrolled 155 adult liver recipients survived more than 3 years after living donor liver transplantation because of non-malignant liver diseases. The maintenance immunosuppressive regimens were TAC monotherapy and combined therapy with mycophenolate mofetil. Patients were divided into three groups according to their late-period TAC trough levels: < 3 ng/mL group, 3-5 ng/mL group, and  >5 ng/mL group. The complications and adverse effects of TAC were analyzed. RESULTS: Each group showed similar rejection, graft loss and mortality. Patients achieved the < 5 ng/mL state in less than 4 years had fewer new-onset diabetes, hyperlipidemia, de novo malignancies, and hepatitis B virus recurrence; the complications of renal dysfunction and hypertension rates were the same among these 3 groups. CONCLUSIONS: Collectively, our findings indicated that lower TAC trough levels in the late period of liver transplantation are safe, improve the long-term outcomes.

Assessing residual vestibular function in adults with congenital hearing loss.

This study adopted an inner ear test battery in adults with congenital hearing loss to assess residual vestibular function. Thirty patients with non-inherited non-syndromatic congenital hearing loss were assigned to two groups based on their pure tone average (PTA). Subjects in Group A (n = 10) had PTA >90 dB, and those with PTA ≤90 dB were assigned to Group B (n = 20). All patients underwent audiometry, and ocular vestibular-evoked myogenic potential (oVEMP), cervical VEMP (cVEMP) and caloric tests. Percentages of abnormal PTA, and cVEMP, oVEMP, and caloric test results showed a significantly sequential decline in inner ear deficits from the cochlea to the saccule, utricle, and semicircular canals. Group A had significantly higher percentages of absent oVEMP and caloric areflexia than Group B. Via receiver operating characteristic curve analysis, the cutoff value of PTA was 65 dB for discriminating between present and absent oVEMP/caloric responses, with a sensitivity of 71 % and a specificity of 88 %. In conclusion, congenitally deaf patients with PTA ≥65 dB may retain less vestibular function than those with PTA <65 dB, as evidenced by higher percentages of absent oVEMP and caloric areflexia. Hence, comprehensive assessment of the residual vestibular function in congenitally deaf patients may help predict the occurrence of vertigo in the future.

Anti-virus prophylaxis withdrawal may be feasible in liver transplant recipients whose serum HBeAg and HBV DNA are negative.

Anti-virus prophylactic therapy may be not necessary for the prevention of hepatitis B virus (HBV) recurrence after HBV-related liver transplantation (LT). However, studies on completely stopping the hepatitis B immune globulin (HBIG) and nucleos(t)ide analogs (NUC) after LT are few. The aim of the current study was to evaluate the safety of anti-virus prophylaxis withdrawal in liver recipients whose serum hepatitis B e antigen (HBeAg) and HBV DNA are negative. We analyzed 190 patients undergone LT for HBV-related liver disease from 2006 to 2012 and found that 10 patients completely stopped the HBIG and NUC due to poor compliance. These patients were liver biopsied and checked monthly with serum HBV markers, HBV DNA and liver function. Among the 10 patients, 9 did not show the signs of HBV recurrence after a mean follow-up of 51.6 months (range 20-73) after withdrawal of the HBIG and NUC. The average time from LT to the withdrawal of the anti-virus drug was 23.8 (13-42) months; one patient showed hepatitis B surface antigen-positive and detectable HBV DNA after stopping anti-virus drugs and this patient was successfully treated with entecavir. Our data suggested that complete withdrawal of anti-virus prophylaxis was safe and feasible for patients whose serum HBeAg and HBV DNA were negative at the time of LT.

The predictive value of blood neutrophil-lymphocyte ratio in patients with end-stage liver cirrhosis following ABO-incompatible liver transplantation.

BACKGROUND: The study was designed to assess the role of preoperative neutrophil, lymphocyte, and neutrophil-lymphocyte ratio (NLR) in predicting survival outcomes of ABO-incompatible liver transplantation (LT). MATERIALS AND METHODS: We retrospectively collected the demographic and clinical characteristics of 71 patients with end-stage liver cirrhosis following ABO-incompatible LT in this study. Kaplan-Meier survival analysis and Cox multiple factors regression analysis were performed to determine the independent risk factors from preoperative blood parameters for poor prognosis. RESULTS: The 1-, 3-, and 5-year overall survival were 94.9%, 80.0%, and 80.0% in the normal NLR group, respectively, and 59.4%, 55,4%, and 55.4% in patients with up-regulated NLR, respectively (P = 0.001). Furthermore, no significant difference was observed on post-LT complications between normal NLR and high-NLR groups. The high NLR was identified as the only independent prognostic risk factor for recipient survival (P = 0.015, 95% confidence interval = 3.573 [1.284-9.943]). CONCLUSION: The preoperative high NLR could be considered as a convenient and available indicator for selecting ABO-incompatible LT candidates.

Absolute lymphocyte count recovery at 1 month after transplantation predicts favorable outcomes of patients with hepatocellular carcinoma.

BACKGROUND AND AIMS: Absolute lymphocyte count (ALC) and the recovery of ALC after treatment have been identified as a prognostic biomarker for several malignancies. In this study, we aimed to investigate the prognostic role of peritransplant ALC and ALC recovery after liver transplantation (LT) in hepatocellular carcinoma (HCC) patients. METHODS: A total of 269 HCC patients undergoing LT were enrolled in our study. Clinicopathological data were retrospectively collected and reviewed. Peritransplant ALC and the change of ALC (2 weeks, 1 month, 3 months post-LT) were carefully monitored. All potential risk factors were analyzed by univariate and multivariate cox regression analysis. RESULTS: Over a mean follow-up of 35.9 months, 120 recurrences and 89 deaths were recorded. In the multivariate analysis, HCC with ALC no recovery at 1 month after LT (P < 0.001), high pretransplant alpha fetoprotein (P = 0.010), total tumor size > 8 cm (P = 0.003), and beyond Milan criteria (P < 0.001) were four independent risk factors for HCC recurrence. For overall survival (OS) after LT, ALC no recovery at 1 month after LT (P = 0.003), total tumor size > 8 cm (P = 0.011), pretransplant albumin < 2.8 g/dL (P = 0.049), model of end-stage liver disease score > 15 (P = 0.017), and beyond Milan criteria (P = 0.001) were significantly related to poor OS. When subgroup analyses were performed according to the Milan criteria, the results showed that the recovery of ALC at 1 month after LT still indicated longer recurrence-free survival (RFS) (P < 0.001) and OS (P = 0.005) beyond Milan criteria as well as RFS (P < 0.001) within Milan criteria, but not OS (P = 0.157) within Milan criteria. CONCLUSIONS: ALC recovery at 1 month after LT indicated favorable outcomes of HCC patients.

The evaluation of enteric-coated mycophenolate sodium in cardiac deceased donor liver transplant patients in China.

OBJECTIVE: The management of liver receivers requires intense immunosuppression to prevent graft rejection. Mycophenolate mofetil (MMF) is a common immunosuppressant but frequently suffer dose reduction for gastrointestinal adverse reactions (GI). Hence, the enteric-coated mycophenolate sodium (EC-MPS) is introduced as a substitute for MMF to reduce GI. The study was designed to investigate the efficacy, safety and exposure equation of EC-MPS in liver transplant patients in China. METHODS: Ninety-two liver receivers who administered EC-MPS or MMF as a primary immunosuppressant were enrolled in this single-center study and divided into MMF group and EC-MPC group, respectively. Efficacy and safety of EC-MPS were compared with MMF. The MPA exposure was measured at time 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 h after mean 4.5 days of EC-MPS treatment. An equation of limited time points for estimating serum MPA exposure of EC-MPS was established using multiple stepwise regression model. RESULTS: Data show an interpatient variation in MPA AUC, Cmax and Tmax. After a first dose of EC-MPS, the mean value of serum AUC0-12 h was 20.68 mg/L (SD 8.94, range 8.1-46.3). Cmax was 9.7 mg/L (SD 6.48, range 2.7-16.3); Tmax was 1.90 h (SD 0.97, range 0.5-4). The best equation for estimating the AUC was 6.0 1 4 + 0.946C2 + 0.606C3 + 1.154C4 + 2.479C6 + 5.07C12. Comparing with MMF, EC-MPS not only effectively maintained immunosuppression, but also had similar incidences of infection, renal dysfunction and hematological disorders. However, EC-MPS markedly improved GI, the incidence of GI was half of the MMF group. CONCLUSION: This analysis presented that EC-MPS is an effective and safe immunosuppressant as similar as MMF. The conversion of MMF to EC-MPS could be administered.

Photovoltaic electrical properties of aqueous grown ZnO antireflective nanostructure on Cu(In,Ga)Se2 thin film solar cells.

A solution-grown subwavelength antireflection coating has been investigated for enhancing the photovoltaic efficiency of thin film solar cells. The 100-nm-height ZnO nanorods coating benefited the photocurrent of Cu(In,Ga)Se2 solar cells from 31.7 to 34.5 mA/cm2 via the decrease of surface light reflectance from 14.5% to 7.0%, contributed by the gradual refractive index profile between air and AZO window layer. The further reduction of surface reflectance to 2.3% in the case of 540-nm-height nanorods, yet, lowered the photocurrent to 29.5 mA/cm2, attributed to the decrease in transmittance. The absorption effect of hydrothermal grown ZnO nanorods was explored to optimize the antireflection function in enhancing photovoltaic performances.