A gut-brain-gut interoceptive circuit loop gates sugar ingestion in Drosophila.

The communication between the brain and digestive tract is critical for optimising nutrient preference and food intake, yet the underlying neural mechanisms remain poorly understood1-7. Here, we show that a gut-brain-gut circuit loop gates sugar ingestion in flies. We discovered that brain neurons regulating food ingestion, IN18, receive excitatory input from enteric sensory neurons, which innervate the oesophagus and express the sugar receptor Gr43a. These enteric sensory neurons monitor the sugar content of food within the oesophagus during ingestion and send positive feedback signals to IN1s, stimulating the consumption of high-sugar foods. Connectome analyses reveal that IN1s form a core ingestion circuit. This interoceptive circuit receives synaptic input from enteric afferents and provides synaptic output to enteric motor neurons, which modulate the activity of muscles at the entry segments of the crop, a stomach-like food storage organ. While IN1s are persistently activated upon ingestion of sugar-rich foods, enteric motor neurons are continuously inhibited, causing the crop muscles to relax and enabling flies to consume large volumes of sugar. Our findings reveal a key interoceptive mechanism that underlies the rapid sensory monitoring and motor control of sugar ingestion within the digestive tract, optimising the diet of flies across varying metabolic states.

Boosting the Efficiency of Perovskite/Organic Tandem Solar Cells via Enhanced Near-Infrared Absorption and Minimized Energy Losses.

The compatibility of perovskite and organic photovoltaic materials in solution processing provides a significant advantage in the fabrication of high-efficiency perovskite/organic tandem solar cells. However, additional recombination losses can occur during exciton dissociation in organic materials, leading to energy losses in the near-infrared region of tandem devices. Consequently, a ternary organic rear subcell is designed containing two narrow-bandgap non-fullerene acceptors to enhance the absorption of near-infrared light. Simultaneously, a unique diffusion-controlled growth technique is adopted to optimize the morphology of the ternary active layer, thereby improving exciton dissociation efficiency. This innovation not only broadens the absorption range of near-infrared light but also facilitates the generation and effective dissociation of excitons. Owing to these technological improvements, the power conversion efficiency (PCE) of organic solar cells increased to 19.2%. Furthermore, a wide-bandgap perovskite front subcell is integrated with a narrow-bandgap organic rear subcell to develop a perovskite/organic tandem solar cell. Owing to the reduction in near-infrared energy loss, the PCE of this tandem device significantly improved, reaching 24.5%.

Blocking ACSL6 Compromises Autophagy via FLI1-Mediated Downregulation of COLs to Radiosensitize Lung Cancer.

Lung cancer (LC) is the leading cause of cancer-related mortality worldwide. Radiotherapy is the main component of LC treatment; however, its efficacy is often limited by radioresistance development, resulting in unsatisfactory clinical outcomes. Here, we found that LC radiosensitivity is up-regulated by decreased expression of long-chain acyl-CoA synthase 6 (ACSL6) after irradiation. Deletion of ACSL6 results in significant elevation of Friend leukemia integration 1 transcription factor (FLI1) and a marked decline of collagens (COLs). Blocking of ACSL6 impairs the tumor growth and upregulates FLI1, which reduces the levels of COLs and compromises irradiation-induced autophagy, leading to considerable therapeutic benefits during radiotherapy. Moreover, the direct interaction between ACSL6 and FLI1 and engagement between FLI1 and COLs indicates the involvement of the ACSL6-FLI1-COL axis. Finally, the potently adjusted autophagy flux reduces its otherwise contributive capability in surviving irradiation stress and leads to satisfactory radiosensitization for LC radiotherapy. These results demonstrate that enhanced ACSL6 expression promotes the aggressive performance of irradiated LC through increased FLI1-COL-mediated autophagy flux. Thus, the ACSL6-FLI1-Col-autophagy axis may be targeted to enhance the radiosensitivity of LC and improve the management of LC in radiotherapy.

Innovative regression model-based decision support tool for optimizing radiotherapy techniques in thoracic esophageal cancer.

Background: Modern radiotherapy exemplified by intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT), has transformed esophageal cancer treatment. Facing challenges in treating thoracic esophageal cancer near vital organs, this study introduces a regression model-based decision support tool for the optimal selection of radiotherapy techniques. Methods: We enrolled 106 patients diagnosed with locally advanced thoracic esophageal cancer in this study and designed individualized IMRT and VMAT radiotherapy plans for each patient. Detailed dosimetric analysis was performed to evaluate the differences in dose distribution between the two radiotherapy techniques across various thoracic regions. Single-factor and multifactorial logistic regression analyses were employed to establish predictive models (P1 and P2) and factors such as TLV/PTV ratio. These models were used to predict the compliance and potential advantages of IMRT and VMAT plans. External validation was performed in a validation group of 30 patients. Results: Using predictive models, we developed a data-driven decision support tool. For upper thoracic cases, VMAT plans were recommended; for middle/lower thoracic cases, the tool guided VMAT/IMRT choices based on TLV/PTV ratio. Models P1 and P2 assessed IMRT and VMAT compliance. In validation, the tool showed high specificity (90.91%) and sensitivity (78.95%), differentiating IMRT and VMAT plans. Balanced performance in compliance assessment demonstrated tool reliability. Conclusion: In summary, our regression model-based decision support tool provides practical guidance for selecting optimal radiotherapy techniques for thoracic esophageal cancer patients. Despite a limited sample size, the tool demonstrates potential clinical benefits, alleviating manual planning burdens and ensuring precise, individualized treatment decisions for patients.

Exacerbation of atherosclerosis by STX17 knockdown: Unravelling the role of autophagy and inflammation.

Syntaxin 17 (STX17) has been identified as a crucial factor in mediating the fusion of autophagosomes and lysosomes. However, its specific involvement in the context of atherosclerosis (AS) remains unclear. This study sought to elucidate the role and mechanistic contributions of STX17 in the initiation and progression of AS. Utilizing both in vivo and in vitro AS model systems, we employed ApoE knockout (KO) mice subjected to a high-fat diet and human umbilical vein endothelial cells (HUVECs) treated with oxidized low-density lipoprotein (ox-LDL) to assess STX17 expression. To investigate underlying mechanisms, we employed shRNA-STX17 lentivirus to knock down STX17 expression, followed by evaluating autophagy and inflammation in HUVECs. In both in vivo and in vitro AS models, STX17 expression was significantly upregulated. Knockdown of STX17 exacerbated HUVEC damage, both with and without ox-LDL treatment. Additionally, we observed that STX17 knockdown impaired autophagosome degradation, impeded autophagy flux and also resulted in the accumulation of dysfunctional lysosomes in HUVECs. Moreover, STX17 knockdown intensified the inflammatory response following ox-LDL treatment in HUVECs. Further mechanistic exploration revealed an association between STX17 and STING; reducing STX17 expression increased STING levels. Further knockdown of STING enhanced autophagy flux. In summary, our findings suggest that STX17 knockdown worsens AS by impeding autophagy flux and amplifying the inflammatory response. Additionally, the interaction between STX17 and STING may play a crucial role in STX17-mediated autophagy.

CA IX-targeted Ag2S quantum dots bioprobe for NIR-II imaging-guided hypoxia tumor chemo-photothermal therapy.

Hypoxia is the common characteristic of almost all solid tumors, which prevents therapeutic drugs from reaching the tumors. Therefore, the development of new targeted agents for the accurate diagnosis of hypoxia tumors is widely concerned. As carbonic anhydrase IX (CA IX) is abundantly distributed on the hypoxia tumor cells, it is considered as a potential tumor biomarker. 4-(2-Aminoethyl)benzenesulfonamide (ABS) as a CA IX inhibitor has inherent inhibitory activity and good targeting effect. In this study, Ag2S quantum dots (QDs) were used as the carrier to prepare a novel diagnostic and therapeutic bioprobe (Ag2S@polyethylene glycol (PEG)-ABS) through ligand exchange and amide condensation reaction. Ag2S@PEG-ABS can selectively target tumors by surface-modified ABS and achieve accurate tumor imaging by the near infrared-II (NIR-II) fluorescence characteristics of Ag2S QDs. PEG modification of Ag2S QDs greatly improves its water solubility and stability, and therefore achieves high photothermal stability and high photothermal conversion efficiency (PCE) of 45.17%. Under laser irradiation, Ag2S@PEG-ABS has powerful photothermal and inherent antitumor combinations on colon cancer cells (CT-26) in vitro. It also has been proved that Ag2S@PEG-ABS can realize the effective treatment of hypoxia tumors in vivo and show good biocompatibility. Therefore, it is a new efficient integrated platform for the diagnosis and treatment of hypoxia tumors.

A novel MAP kinase-interacting protein MoSmi1 regulates development and pathogenicity in Magnaporthe oryzae.

The cell wall is the first barrier against external adversity and plays roles in maintaining normal physiological functions of fungi. Previously, we reported a nucleosome assembly protein, MoNap1, in Magnaporthe oryzae that plays a role in cell wall integrity (CWI), stress response, and pathogenicity. Moreover, MoNap1 negatively regulates the expression of MoSMI1 encoded by MGG_03970. Here, we demonstrated that deletion of MoSMI1 resulted in a significant defect in appressorium function, CWI, cell morphology, and pathogenicity. Further investigation revealed that MoSmi1 interacted with MoOsm1 and MoMps1 and affected the phosphorylation levels of MoOsm1, MoMps1, and MoPmk1, suggesting that MoSmi1 regulates biological functions by mediating mitogen-activated protein kinase (MAPK) signalling pathway in M. oryzae. In addition, transcriptome data revealed that MoSmi1 regulates many infection-related processes in M. oryzae, such as membrane-related pathway and oxidation reduction process. In conclusion, our study demonstrated that MoSmi1 regulates CWI by mediating the MAPK pathway to affect development and pathogenicity of M. oryzae.

Hierarchical Solid-Additive Strategy for Achieving Layer-by-Layer Organic Solar Cells with Over 19 % Efficiency.

Layer-by-layer (LbL) deposition of active layers in organic solar cells (OSCs) offers immense potential for optimizing performance through precise tailoring of each layer. However, achieving high-performance LbL OSCs with distinct solid additives in each layer remains challenging. In this study, we explore a novel approach that strategically incorporates different solid additives into specific layers of LbL devices. To this end, we introduce FeCl3 into the lower donor (D18) layer as a p-type dopant to enhance hole concentration and mobility. Concurrently, we incorporate the wide-band gap conjugated polymer poly(9,9-di-n-octylfluorenyl-2,7-diyl) (PFO) into the upper acceptor (L8-BO) layer to improve the morphology and prolong exciton lifetime. Unlike previous studies, our approach combines these two strategies to achieve higher and more balanced electron and hole mobility without affecting device open-circuit voltage, while also suppressing charge recombination. Consequently, the power conversion efficiency (PCE) of the D18+FeCl3/L8-BO device increases to 18.12 %, while the D18/L8-BO+PFO device attains a PCE of 18.79 %. These values represent substantial improvements over the control device's PCE of 17.59 %. Notably, when both FeCl3 and PFO are incorporated, the D18+FeCl3/L8-BO+PFO device achieves a remarkable PCE of 19.17 %. In summary, our research results demonstrate the effectiveness of the layered solid additive strategy in improving OSC performance.

HisCl1 regulates gustatory habituation in sweet taste neurons and mediates sugar ingestion in Drosophila.

Similar to other animals, the fly, Drosophila melanogaster, reduces its responsiveness to tastants with repeated exposure, a phenomenon called gustatory habituation. Previous studies have focused on the circuit basis of gustatory habituation in the fly chemosensory system1,2. However, gustatory neurons reduce their firing rate during repeated stimulation3, suggesting that cell-autonomous mechanisms also contribute to habituation. Here, we used deep learning-based pose estimation and optogenetic stimulation to demonstrate that continuous activation of sweet taste neurons causes gustatory habituation in flies. We conducted a transgenic RNAi screen to identify genes involved in this process and found that knocking down Histamine-gated chloride channel subunit 1 (HisCl1) in the sweet taste neurons significantly reduced gustatory habituation. Anatomical analysis showed that HisCl1 is expressed in the sweet taste neurons of various chemosensory organs. Using single sensilla electrophysiology, we showed that sweet taste neurons reduced their firing rate with prolonged exposure to sucrose. Knocking down HisCl1 in sweet taste neurons suppressed gustatory habituation by reducing the spike frequency adaptation observed in these neurons during high-concentration sucrose stimulation. Finally, we showed that flies lacking HisCl1 in sweet taste neurons increased their consumption of high-concentration sucrose solution at their first meal bout compared to control flies. Together, our results demonstrate that HisCl1 tunes spike frequency adaptation in sweet taste neurons and contributes to gustatory habituation and food intake regulation in flies. Since HisCl1 is highly conserved across many dipteran and hymenopteran species, our findings open a new direction in studying insect gustatory habituation.

Radiation-induced upregulation of FGL1 promotes esophageal squamous cell carcinoma metastasis via IMPDH1.

BACKGROUND: While radiation therapy remains pivotal in esophageal squamous cell carcinoma (ESCC) treatment, the perplexing phenomenon of post-radiation metastasis presents a formidable clinical challenge. This study investigates the role of fibrinogen-like protein 1 (FGL1) in driving ESCC metastasis following radiation exposure. METHODS: FGL1 expression in post-radiation ESCC cells was meticulously examined using qRT-PCR, western blotting, and immunofluorescence. The impact of FGL1 on ESCC cell invasion and migration was assessed through Transwell and wound healing assays. In vivo, the metastatic potential of ESCC in response to FGL1 was scrutinized using nude mice models. Comprehensive RNA sequencing and functional experiments elucidated the intricate mechanism associated with FGL1. RESULTS: Radiation induced upregulation of FGL1 in ESCC cells through FOXO4, intensifying ESCC cell invasion and migration. Targeted knockdown of FGL1 effectively alleviated these characteristics both in vitro and in vivo. FGL1 depletion concurrently suppressed IMPDH1 expression. Rescue experiments underscored that IMPDH1 knockdown robustly reversed the pro-invasive effects induced by FGL1 in ESCC cells. ESCC tissues exhibited heightened IMPDH1 mRNA levels, demonstrating a correlation with patient survival. CONCLUSIONS: Radiation-induced upregulation of FGL1 propels ESCC metastasis through IMPDH1, proposing a potential therapeutic target to mitigate post-radiotherapy metastasis in ESCC patients.

TYG Index as a Novel Predictor of Clinical Outcomes in Advanced Chronic Heart Failure with Renal Dysfunction Patients.

Background: The triglyceride-glucose (TYG) index is a novel and reliable marker reflecting insulin resistance. Its predictive ability for cardiovascular disease onset and prognosis has been confirmed. However, for advanced chronic heart failure (acHF) patients, the prognostic value of TYG is challenged due to the often accompanying renal dysfunction (RD). Therefore, this study focuses on patients with aHF accompanied by RD to investigate the predictive value of the TYG index for their prognosis. Methods and Results: 717 acHF with RD patients were included. The acHF diagnosis was based on the 2021 ESC criteria for acHF. RD was defined as the eGFR < 90 mL/(min/1.73 m2). Patients were divided into two groups based on their TYG index values. The primary endpoint was major adverse cardiovascular events (MACEs), and the secondary endpoints is all-cause mortality (ACM). The follow-up duration was 21.58 (17.98-25.39) months. The optimal cutoff values for predicting MACEs and ACM were determined using ROC curves. Hazard factors for MACEs and ACM were revealed through univariate and multivariate COX regression analyses. According to the univariate COX regression analysis, high TyG index was identified as a risk factor for MACEs (hazard ratio = 5.198; 95% confidence interval [CI], 3.702-7.298; P < 0.001) and ACM (hazard ratio = 4.461; 95% CI, 2.962-6.718; P < 0.001). The multivariate COX regression analysis showed that patients in the high TyG group experienced 440.2% MACEs risk increase (95% CI, 3.771-7.739; P < 0.001) and 406.2% ACM risk increase (95% CI, 3.268-7.839; P < 0.001). Kaplan-Meier survival analysis revealed that patients with high TyG index levels had an elevated risk of experiencing MACEs and ACM within 30 months. Conclusion: This study found that patients with high TYG index had an increased risk of MACEs and ACM, and the TYG index can serve as an independent predictor for prognosis.

Xylanase VmXyl2 is involved in the pathogenicity of Valsa mali by regulating xylanase activity and inducing cell necrosis.

Xylanase plays a key role in degrading plant cell wall during pathogenic fungi infection. Here, we identified a xylanase gene, VmXyl2 from the transcriptome of Valsa mali and examined its function. VmXyl2 has highly elevated transcript levels during the infection process of V. mali, with 15.02-fold increase. Deletion mutants of the gene were generated to investigate the necessity of VmXyl2 in the development and pathogenicity of V. mali. The VmXyl2 deletion mutant considerably reduced the virulence of V. mali in apple leaves and in twigs, accompanied by 41.22% decrease in xylanase activity. In addition, we found that VmXyl2 induces plant cell necrosis regardless of its xylanase activity, whereas promoting the infection of V. mali in apple tissues. The cell death-inducing activity of VmXyl2 dependent on BRI1-associated kinase-1 (BAK1) but not Suppressor of BIR1-1 (SOBIR1). Furthermore, VmXyl2 interacts with Mp2 in vivo, a receptor-like kinase with leucine-rich repeat. The results offer valuable insights into the roles of VmXyl2 in the pathogenicity of V. mali during its infection of apple trees.

Protein Multiple Conformation Prediction Using Multi-Objective Evolution Algorithm.

The breakthrough of AlphaFold2 and the publication of AlphaFold DB represent a significant advance in the field of predicting static protein structures. However, AlphaFold2 models tend to represent a single static structure, and multiple-conformation prediction remains a challenge. In this work, we proposed a method named MultiSFold, which uses a distance-based multi-objective evolutionary algorithm to predict multiple conformations. To begin, multiple energy landscapes are constructed using different competing constraints generated by deep learning. Subsequently, an iterative modal exploration and exploitation strategy is designed to sample conformations, incorporating multi-objective optimization, geometric optimization and structural similarity clustering. Finally, the final population is generated using a loop-specific sampling strategy to adjust the spatial orientations. MultiSFold was evaluated against state-of-the-art methods using a benchmark set containing 80 protein targets, each characterized by two representative conformational states. Based on the proposed metric, MultiSFold achieves a remarkable success ratio of 56.25% in predicting multiple conformations, while AlphaFold2 only achieves 10.00%, which may indicate that conformational sampling combined with knowledge gained through deep learning has the potential to generate conformations spanning the range between different conformational states. In addition, MultiSFold was tested on 244 human proteins with low structural accuracy in AlphaFold DB to test whether it could further improve the accuracy of static structures. The experimental results demonstrate the performance of MultiSFold, with a TM-score better than that of AlphaFold2 by 2.97% and RoseTTAFold by 7.72%. The online server is at http://zhanglab-bioinf.com/MultiSFold .

Correction: Li et al. Fabrication of Poly Dopamine@poly (Lactic Acid-Co-Glycolic Acid) Nanohybrids for Cancer Therapy via a Triple Collaboration Strategy. Nanomaterials 2023, 13, 1447.

The authors regret that, in the published article [...].

Recent Advances of Green Electricity Generation: Potential in Solar Interfacial Evaporation System.

Solar-driven interfacial evaporation (SDIE) has played a pivotal role in optimizing water-energy utilization, reducing conventional power costs, and mitigating environmental impacts. The increasing emphasis on the synergistic cogeneration of water and green electricity through SDIE is particularly noteworthy. However, there is a gap of existing reviews that have focused on the mechanistic understanding of green power from water-electricity cogeneration (WEC) systems, the structure-activity relationship between efficiency of green energy utilization in WEC and material design in SDIE. Particularly, it lacks a comprehensive discussion to address the challenges faced in these areas along with potential solutions. Therefore, this review aims to comprehensively assess the progress and future perspective of green electricity from WEC systems by investigating the potential expansion of SDIE. First, it provides a comprehensive overview about material rational design, thermal management, and water transportation tunnels in SDIE. Then, it summarizes diverse energy sources utilized in the SDIE process, including steaming generation, photovoltaics, salinity gradient effect, temperature gradient effect, and piezoelectric effect. Subsequently, it explores factors that affect generated green electricity efficiency in WEC. Finally, this review proposes challenges and possible solution in the development of WEC.

Effect of Cold Deformation and Heat Treatment on the Microstructures and Mechanical Properties of Au-15Ag-12Cu-6Ni Alloy Sheets.

The evolution of the microstructure and hardness changes in the Au-15Ag-12Cu-6Ni alloy during the processes of cold rolling and annealing were investigated and the heat treatment regimen for the alloy was optimized in this article. The hardness of the alloy continuously increases with the cold rolling reductions, leading to continuous deformation of the grains during the cold rolling process, ultimately resulting in smaller grain sizes. Subsequent annealing induces recovery and recrystallization, achieving complete recrystallization at 700 °C. An intriguing softening effect is observed after annealing at 700 °C, manifesting in a significant reduction in hardness to 238 (Hv0.5). The cold deformation texture of the alloy aligns with the recrystallization texture type, exhibiting only a certain degree of angular deviation. This is primarily characterized by <111>//RD texture and a texture deviating 60° from RD towards TD. The performance of the finished sheet improves with the precipitation of ordered phases AuCu after a 300 °C heat treatment for 0.5 h, resulting in a remarkable hardness of 380 (Hv0.5).

Halogenated Nonfused Ring Electron Acceptor for Organic Solar Cells with a Record Efficiency of over 17.

Three nonfused ring electron acceptors (NFREAs), namely, 3TT-C2-F, 3TT-C2-Cl, and 3TT-C2, are purposefully designed and synthesized with the concept of halogenation. The incorporation of F or/and Cl atoms into the molecular structure (3TT-C2-F and 3TT-C2-Cl) enhances the π-π stacking, improves electron mobility, and regulates the nanofiber morphology of blend films, thus facilitating the exciton dissociation and charge transport. In particular, blend films based on D18:3TT-C2-F demonstrate a high charge mobility, an extended exciton diffusion distance, and a well-formed nanofiber network. These factors contribute to devices with a remarkable power conversion efficiency of 17.19%, surpassing that of 3TT-C2-Cl (16.17%) and 3TT-C2 (15.42%). To the best of knowledge, this represents the highest efficiency achieved in NFREA-based devices up to now. These results highlight the potential of halogenation in NFREAs as a promising approach to enhance the performance of organic solar cells.

A Method for the Synthesis of Thioindoles through Copper-Catalyzed C-S Bond Coupling Reaction.

We herein report the copper-catalyzed C-S bond coupling reaction of indoles with N-thiosuccinimides, resulting in moderate to excellent yields of mono- and bis-sulfenylated compounds such as arylthioindoles, alkylthioindoles, selenylated indoles, and cysteine-substituted indoles. Thioarylation and thioglycosylation at the C2 position of indole alkaloids in the Radix Isatidis were achieved via structural modification. The first total syntheses of isatindigotindolosides III and IV have been successfully carried out. The electrophilic sulfenyl bromides generated in situ can play an important role in the catalytic cycle.

Periostin-targeted SDSSD peptide decorated calcium phosphate nanocomposites incorporation with simvastatin for osteoporosis treatment.

The limited options of anabolic drugs restrict their application potential in osteoporosis treatment, despite their theoretical superiority in therapeutic efficacy over antiresorptive drugs. As a prevailing strategy, nano-delivery systems could offer a wider choice of anabolic drugs. In this study, calcium phosphate nanocomposites incorporated with simvastatin (Sim) with periostin-targeting ability were designed and prepared for osteoporosis treatment. Carboxymethyl dextran (CMD) as an anionic and hydrophilic dextran derivative was used to stabilize CaP. In addition, periosteum-targeted peptide (SDSSD) was further grafted on CMD to achieve the bone targeting function. In a one-step coordination assembly strategy, hydrophobic anabolic agent Sim and SDSSD-CMD graft (SDSSD-CMD) were incorporated into the CaP nanoparticles forming SDSSD@CaP/Sim nanocomposites. The resulting SDSSD@CaP/Sim possesses uniform size, great short-term stability and excellent biocompatibility. Moreover, SDSSD@CaP/Sim exhibited a reduced release rate of Sim and showed slow-release behaviour. As anticipated, the nanocomposites exhibited bone bonding capacity in both cellular and animal studies. Besides, SDSSD@CaP/Sim achieved obviously enhanced osteoporosis treatment effect compared to direct injection of Simin vivo. Therefore, our findings highlight the potential of SDSSD-incorporated and CaP-based nanocomposites as a viable strategy to enhance the therapeutic efficacy of anabolic drugs for osteoporosis treatment.

Visual feedback neurons fine-tune Drosophila male courtship via GABA-mediated inhibition.

Many species of animals use vision to regulate their social behaviors. However, the molecular and circuit mechanisms underlying visually guided social interactions remain largely unknown. Here, we show that the Drosophila ortholog of the human GABAA-receptor-associated protein (GABARAP) is required in a class of visual feedback neurons, lamina tangential (Lat) cells, to fine-tune male courtship. GABARAP is a ubiquitin-like protein that maintains cell-surface levels of GABAA receptors. We demonstrate that knocking down GABARAP or GABAAreceptors in Lat neurons or hyperactivating them induces male courtship toward other males. Inhibiting Lat neurons, on the other hand, delays copulation by impairing the ability of males to follow females. Remarkably, the fly GABARAP protein and its human ortholog share a strong sequence identity, and the fly GABARAP function in Lat neurons can be rescued by its human ortholog. Using in vivo two-photon imaging and optogenetics, we reveal that Lat neurons are functionally connected to neural circuits that mediate visually guided courtship pursuits in males. Our work identifies a novel physiological function for GABARAP in regulating visually guided courtship pursuits in Drosophila males. Reduced GABAA signaling has been linked to social deficits observed in the autism spectrum and bipolar disorders. The functional similarity between the human and the fly GABARAP raises the possibility of a conserved role for this gene in regulating social behaviors across insects and mammals.