[Corrigendum] (­)­Epigallocatechingallate induces apoptosis in B lymphoma cells via caspase­dependent pathway and Bcl­2 family protein modulation.

Subsequently to the publication of the above article, an interested reader drew to the authors' attention that, in Fig. 3 on p. 1510, the western blot images selected to portray the caspase 7 and PARP/cleaved PARP experiments were remarkably similar. After having referred to their original data, the authors realized that the PARP/cleaved PARP blots had been inadvertently duplicated in the figure. The revised version of Fig. 3, showing the correct data for the caspase­7 experiment, is shown below. The authors confirm that the errors made during the assembly of Fig. 3 did not adversely affect the major conclusions presented in this paper, and are grateful to the Editor of International Journal of Oncology for allowing them this opportunity to publish a corrigendum. They also apologize to the readership for any inconvenience caused. [International Journal of Oncology 46: 1507­1515, 2015; DOI: 10.3892/ijo.2015.2869].

scPriorGraph: constructing biosemantic cell-cell graphs with prior gene set selection for cell type identification from scRNA-seq data.

Cell type identification is an indispensable analytical step in single-cell data analyses. To address the high noise stemming from gene expression data, existing computational methods often overlook the biologically meaningful relationships between genes, opting to reduce all genes to a unified data space. We assume that such relationships can aid in characterizing cell type features and improving cell type recognition accuracy. To this end, we introduce scPriorGraph, a dual-channel graph neural network that integrates multi-level gene biosemantics. Experimental results demonstrate that scPriorGraph effectively aggregates feature values of similar cells using high-quality graphs, achieving state-of-the-art performance in cell type identification.

Disorders of compulsivity: Deficits in arbitrating learning strategies.

While previous research has shown that compulsivity is related to an imbalance between goal-directed and habitual learning systems, very little is known about whether this effect is due to the impairment of a single system or the impairment of the arbitration mechanism that determines which system controls behaviour at any given moment; the current study aims to address this disagreement. Nineteen alcohol use disorder, 30 obsessive-compulsive disorder (OCD) and 20 major depressive disorder patients and corresponding sex- and age-matched controls performed two-choice, three-stage Markov decision-making paradigm. Model-based and mode-free reinforcement learning models were used to independently fitted their behavioural data. Alcohol use disorder and OCD patients showed less model-based strategy choice than healthy controls in task conditions where the model-based strategy was optimal. Only OCD patients showed higher behavioural control system switching in task conditions where model-free use was optimal. Major depressive disorder patients did not differ from the matched control in both. These findings suggest that dysfunction in arbitration control between dual systems may be the basis for diverse disorders involving compulsivity.

Sequential bowel necrosis and large gastric ulcer in a patient with a ruptured femoral artery: A case report.

BACKGROUND: Severe bleeding as a result of a major vascular injury is a potentially fatal event commonly observed in the emergency department. Bowel necrosis and gastric ulcers secondary to ischemia are rare due to their rich blood supply. In this case, we present the case of a patient who was treated successfully following rupture of his femoral artery resulting in bowel necrosis and an unusually large gastric ulcer. CASE SUMMARY: A 28-year-old male patient sustained a knife stab wound to the right thigh, causing rupture of his femoral artery and leading to massive bleeding. He underwent cardiopulmonary resuscitation and received a large blood transfusion. Abdominal surgeries confirmed bowel necrosis, and jejunostomy was performed. The necrotic intestine was removed, the remaining intestine was anastomosed, and the right thigh was amputated. After three surgeries, the patient's overall condition gradually improved, and the patient was discharged from the hospital. However, one day after discharge, the patient was admitted again due to dizziness and melena, and a gastroduodenoscopy revealed a giant banded ulcer. After 2 weeks of treatment, the ulcer had decreased in size without bleeding. Six months after the last surgery, enterostomy and reintroduction surgery were completed. The patient was fitted with a right lower limb prosthesis one year after surgery. After 3 years of follow-up, the patient did not complain of discomfort. CONCLUSION: Trauma department physicians need to be aware of the possible serious complications involving the abdomen of trauma patients with massive bleeding.

Adjunctive benefits of low-frequency transcutaneous electrical nerve stimulation for obesity frequent chronic conditions: a systematic review.

Background: Obesity is widely recognized for its role in predisposing individuals to a spectrum of chronic health conditions. Emerging preliminary evidence points to the potential benefits of low-frequency transcutaneous electrical nerve stimulation (Lo-TENS) in enhancing various health outcomes among those with obesity and associated disorders. Objective: This systematic review was designed to assess the effectiveness of Lo-TENS for managing obesity and its related chronic diseases. Methods: For this systematic review, we included randomized controlled trials that evaluated the impact of Lo-TENS on individuals with obesity and its associated chronic diseases. Results: Eight trials encompassing 671 participants and spanning three unique populations: essential hypertension (EH), type 2 diabetes mellitus (T2DM), and obesity were deemed eligible for inclusion in this review. Compared to baseline measurements, Lo-TENS demonstrated a tendency to positively affect blood pressure in individuals with EH and metabolic parameters in those with T2DM. Nonetheless, the efficacy of Lo-TENS in treating obesity is not yet clear when contrasted with a no-intervention control group. When compared with other intervention modalities, three of the trials reported less favorable results. Conclusions: Although Lo-TENS did not consistently surpass other treatments or yield substantial improvements, it generally provided greater benefits than the majority of placebo controls. This suggests that Lo-TENS could potentially serve as a beneficial adjunctive therapy in the management of obesity and its associated conditions. However, given the limited number of trials assessed, the elevated risk of bias within these studies, and the scarce evidence currently available, it is too early to reach definitive conclusions. Caution should be exercised when interpreting the current findings. There is an imperative for further high-quality research to thoroughly investigate and substantiate the efficacy of Lo-TENS in relation to obesity and its related disorders.

Worldwide SARS-CoV-2 Omicron variant infection: Emerging sub-variants and future vaccination perspectives.

The coronavirus disease 2019 (COVID-19) pandemic has sparked widespread concern globally, particularly with the Omicron variant and its sub-lineages emerging as the predominant cause of infection for nearly two years. Taiwan's successful containment of COVID-19, underscored by broad vaccine coverage, the utilization of anti-viral therapeutics, and timely response strategies, has resulted in reduced excess mortality. Moreover, there is a crucial need for a phased exit strategy, balancing efforts to curtail disease transmission with the mitigation of socioeconomic impacts from rigorous measures. In this review, we examined the evolution and the epidemiological landscape of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sub-variants in Taiwan as well as other countries of the world. We also critically evaluated the effectiveness of COVID-19 vaccines against various SARS-CoV-2 variants. Additionally, we addressed the advantages of heterologous immunization strategies, fluctuations in neutralizing antibody titers, and complexities in establishing protective correlates among swiftly mutating viral variants.

Enhanced De/hydrogenation Kinetics and Cycle Stability of Mg/MgH2 by the MnOx-Coated Ti2CTx Catalyst with Optimized Ti-H Bond Stability.

MXene based catalysts can significantly enhance hydrogenation and dehydrogenation (de/hydrogenation) kinetics of Mg/MgH2, but they suffer from uncontrollable catalysts-hydrogen bond strength and structural instability. Here, we propose Tx density control of MXene-based catalysts and MnOx coating as a promising solution. The MnOx@Ti2CTx-catalyzed Mg/MgH2 can release 5.97 wt % H2 at 300 °C in 3 min and 5.60 wt % H2 at 240 °C in 15 min with an activation energy of 75.57 kJ·mol-1. In addition, the samples showed excellent de/hydrogenation-cycle stability, and the degradation of hydrogen storage capacity is negligible even after 100 cycles. DFT calculations combined with XPS analysis showed that the Tx defect on the surface of the MnOx@Ti2CTx catalyst could optimize the strength of the Ti-H bond, accelerating both hydrogen dissociation and diffusion processes. The catalyst's surface properties were protected by the MnOx coating, achieving high chemical and catalytic stability. These findings offer a strategy for surface structure optimization and protection of MXene-based catalysts, realizing controllable catalyst-hydrogen bond strength.

Synthesis of non-canonical amino acids through dehydrogenative tailoring.

Amino acids are essential building blocks in biology and chemistry. While nature relies on a small number of amino acid structures, chemists desire access to a vast scope of structurally diverse analogs1-3 The selective modification of amino acid side-chain residues represents an efficient strategy to access non-canonical derivatives of value in chemistry and biology. While semi-synthetic methods leveraging the functional groups found in polar and aromatic amino acids have been extensively explored, highly selective and general approaches to transform unactivated C-H bonds in aliphatic amino acids remain less developed4,5 Here, we disclose a stepwise dehydrogenative method to convert aliphatic amino acids into structurally diverse analogs. The key to the success of this approach lies in the development of a selective catalytic acceptorless dehydrogenation method driven by photochemical irradiation, which provides access to terminal alkene intermediates for downstream functionalization. Overall, this strategy enables the rapid synthesis of new amino acid building blocks and suggests possibilities for the late-stage modification of more complex oligopeptides.

Public attitudes toward stuttering and cluttering in Chinese and Japanese speech-language pathology students.

PURPOSE: This study utilized the Chinese and Japanese translations of the Public Opinion Survey of Human Attributes-Stuttering (POSHA-S) and Cluttering (POSHA-Cl) to compare the differences in (a) attitudes towards stuttering versus cluttering in speech-language pathology (SLP) students in either China or Japan, (b) attitudes of SLP students in China versus Japan towards either stuttering or cluttering, and (c) attitudes of Chinese and Japanese students versus international databases for stuttering and cluttering. METHOD: The POSHA-S and POSHA-Cl were both administered to 99 SLP students from six universities in China and 352 SLP students from two universities in Japan. RESULTS: Attitudes toward stuttering were markedly different for Chinese versus Japanese students. Overall, stuttering attitudes were slightly more positive than cluttering attitudes in both countries; however, compared to China, Japanese SLP students attitudes toward stuttering and cluttering were more disimilar. In addition, compared with the international database, the attitudes of Chinese and Japanese SLP students toward self-reactions to both disorders were more positive. CONCLUSION: Chinese and Japanese SLP students' attitudes toward both stuttering and cluttering are likely to be influenced by geography, culture, education, and the "halo effect." The attitudes of the SLP students in China and Japan are more negative than the attitudes as shown in the global data.

Fluorogenic Aptamer Optimizations on a Massively Parallel Sequencing Platform.

F luorogenic ap tamers (FAPs) have become an increasingly important tool in cellular sensing and pathogen diagnostics. However, fine-tuning FAPs for enhanced performance remains challenging even with the structural details provided by X-ray crystallography. Here we present a novel approach to optimize a DNA-based FAP (D-FAP), Lettuce, on repurposed Illumina next-generation sequencing (NGS) chips. When substituting its cognate chromophore, DFHBI-1T, with TO1-biotin, Lettuce not only shows a red-shifted emission peak by 53 nm (from 505 to 558 nm), but also a 4-fold bulk fluorescence enhancement. After screening 8,821 Lettuce variants complexed with TO1-biotin, the C14T mutation is found to exhibit an improved apparent dissociated constant ( vs. 0.82 µM), an increased quantum yield (QY: 0.62 vs. 0.59) and an elongated fluorescence lifetime (τ: 6.00 vs. 5.77 ns), giving 45% more ensemble fluorescence than the canonical Lettuce/TO1-biotin complex. Molecular dynamic simulations further indicate that the π-π stacking interaction is key to determining the coordination structure of TO1-biotin in Lettuce. Our screening-and-simulation pipeline can effectively optimize FAPs without any prior structural knowledge of the canonical FAP/chromophore complexes, providing not only improved molecular probes for fluorescence sensing but also insights into aptamer-chromophore interactions.

Alterations in coenzyme Q10 status in a cybrid line harboring the 3243A>G mutation of mitochondrial DNA is associated with abnormal mitochondrial bioenergetics and dysregulated mitochondrial biogenesis.

Mitochondrial DNA (mtDNA) mutations, including the m.3243A>G mutation that causes mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), are associated with secondary coenzyme Q10 (CoQ10) deficiency. We previously demonstrated that PPARGC1A knockdown repressed the expression of PDSS2 and several COQ genes. In the present study, we compared the mitochondrial function, CoQ10 status, and levels of PDSS and COQ proteins and genes between mutant cybrids harboring the m.3243A>G mutation and wild-type cybrids. Decreased mitochondrial energy production, defective respiratory function, and reduced CoQ10 levels were observed in the mutant cybrids. The ubiquinol-10:ubiquinone-10 ratio was lower in the mutant cybrids, indicating blockage of the electron transfer upstream of CoQ, as evident from the reduced ratio upon rotenone treatment and increased ratio upon antimycin A treatment in 143B cells. The mutant cybrids exhibited downregulation of PDSS2 and several COQ genes and upregulation of COQ8A. In these cybrids, the levels of PDSS2, COQ3-a isoform, COQ4, and COQ9 were reduced, whereas those of COQ3-b and COQ8A were elevated. The mutant cybrids had repressed PPARGC1A expression, elevated ATP5A levels, and reduced levels of mtDNA-encoded proteins, nuclear DNA-encoded subunits of respiratory enzyme complexes, MNRR1, cytochrome c, and DHODH, but no change in TFAM, TOM20, and VDAC1 levels. Alterations in the CoQ10 level in MELAS may be associated with mitochondrial energy deficiency and abnormal gene regulation. The finding of a reduction in the ubiquinol-10:ubiquinone-10 ratio in the MELAS mutant cybrids differs from our previous discovery that cybrids harboring the m.8344A>G mutation exhibit a high ubiquinol-10:ubiquinone-10 ratio.

Clinician characteristics associated with fluoride varnish applications during well-child visits.

OBJECTIVES: To identify factors associated with clinicians' likelihood and intensity of applying fluoride varnish (FV) overall and for visits paid by Medicaid and private insurers. STUDY DESIGN: Observational study using claims data. METHODS: Using the Massachusetts All-Payer Claims Database (2016-2018), we conducted a repeated cross-sectional study of 2911 clinicians (7277 clinician-year observations) providing well-child visits to children aged 1 to 5 years. Zero-inflated negative binomial models estimated the probability of a clinician applying FV and the number of visits with FV applications, overall and separately for visits paid by Medicaid and private insurers. RESULTS: A total of 30.9% of clinician-years applied FV at least once, and overall, an average of 8.4% of a clinician's well-child visits included FV annually. Controlling for all covariates, having a higher percentage of patients insured by Medicaid was associated with applying FV (OR, 1.35; 95% CI, 1.23-1.45) and a higher expected number of applications (OR, 1.05; 95% CI, 1.02-1.09). Additionally, having a higher percentage of patients aged 1 to 5 years was associated with applying FV (OR, 1.20; 95% CI, 1.01-1.43), but not the number of applications. Similar associations were observed among visits paid by private insurers. CONCLUSIONS: Despite clinical recommendations and mandated insurance reimbursements, the likelihood and intensity of FV applications was low for most pediatric primary care clinicians. Clinician behavior was associated with patient-panel characteristics, suggesting the need for interventions that account for these differences.

Geographic variation in shortfalls of dementia specialists in the United States.

Dementia specialists-neurologists, geriatricians, and geriatric psychiatrists-serve a critical clinical function in diagnosing early-stage Alzheimer's disease and determining eligibility for treatment with disease-modifying therapies. However, the availability of dementia specialists is limited and varies across the United States. Using data from the Area Health Resources Files, we found that the median density of dementia specialists across hospital referral regions in United States is 28.8 per 100 000 population aged 65 years and older (interquartile range 19.3-43.6). We derived thresholds of 33-45 dementia specialists per 100 000 population aged 65 years and older as the provider density necessary to care for older adults with mild cognitive impairment and dementia. Based on these thresholds, we estimated that 34%-59% of the population aged 65 years and older resided in areas with potential dementia specialist shortfalls. The extent of potential shortfalls varied by state and rurality. A better understanding of potential gaps in the availability of dementia specialists will inform policies and practices to ensure access to services for people with cognitive impairment and dementia.

Efficacy and safety of adjuvant therapies in older patients with breast cancer: a systematic review and meta-analysis of real-world data.

BACKGROUND: Insufficient data available for older patients with breast cancer complicates decision-making regarding optimal treatment. A systematic review that uses real-world data is required for assessing the effectiveness and potential adverse effects of various therapies for this age group of patients. METHODS: Databases of PubMed, Embase, and Cochrane Library were searched. We included clinical studies that evaluated various treatments for geriatric breast cancer, including adjuvant radiation therapy, hypofractionated radiation therapy (hypo-RT) and accelerated and partial breast irradiation (APBI), endocrine therapy, chemotherapy, and targeted therapy. RESULTS: A total of 71 studies were retrieved. Adjuvant radiation therapy significantly improved overall survival (OS) compared with no radiation [hazard ratio (HR) = 0.60, 95% confidence interval (CI) 0.54-0.67]. The pooled estimates of OS for hypo-RT and APBI demonstrated no inferiority compared with conventional radiation. Both endocrine treatment (HR = 0.63, 95% CI 0.43-0.92) and chemotherapy (HR = 0.76, 95% CI 0.65-0.88) significantly increased OS compared with no treatment. Trastuzumab monotherapy significantly enhanced OS compared with no trastuzumab use (HR = 0.23, 95% CI 0.07-0.73). CONCLUSION: Despite concerns about potential complications during treatment in older patients, proactive therapies significantly increase their survival rates. For patients who are frailer, hypo-RT and APBI offer survival rates comparable to traditional modalities. Additionally, targeted therapy as a monotherapy holds promise as a viable option for patients with HER2-positive breast cancer who cannot undergo chemotherapy. Therefore, by conducting thorough general assessments and clinical evaluations, the side effects of postoperative treatments can be effectively managed.

A highly sensitive and colorimetric fluorescent probe for visualizing hydroxylamine in immune cells.

BACKGROUND: Hydroxylamine (HA) is vital industrial raw material and pharmaceutical intermediate. In addition, HA is an important cellular metabolite, which is intermediate in the formation of nitric oxide and nitroxide. However, excessive amounts of HA are toxic to both animals and plants. Conventional methods for the detection of HA are cumbersome and complicated. The detection of HA with fluorescent probes is convenient and sensitive. There are few probes available for the detection of hydroxylamine. Therefore, a fluorescent probe for the sensitive and selective detection of HA was developed in this work. RESULTS: A coumarin derivative SWJT-22 was synthesized as a colorimetric fluorescent probe to detect hydroxylamine (HA), with high sensitivity and selectivity. The detection limit of the probe to HA was 0.15 µM, which was lower than most probes of HA. Upon the addition of HA to aqueous solution containing SWJT-22, the color of the solution changed from orange to yellow, and the fluorescence color also changed from orange to green. The reaction mechanism of SWJT-22 to HA was confirmed by 1H NMR titrations, mass spectrometry and round bottom flask experiments. Moreover, SWJT-22 had been fabricated into portable test strips for the detection of HA. SWJT-22 had been successfully used in cellular imaging and could detect both endogenous and exogenous HA in HeLa cells and RAW 264.7 cells. SIGNIFICANCE: Due to the physiological role of hydroxylamine in organisms, it is crucial to detect hydroxylamine selectively and sensitively. This work provided a convenient tool for the detection of hydroxylamine, not only to detect endogenous and exogenous HA in cells, but also made into portable test strips. The HA fluorescent probe SWJT-22 is expected to promote the study of HA in physiological processes.

Two-photon autofluorescence lifetime assay of rabbit photoreceptors and retinal pigment epithelium during light-dark visual cycles in rabbit retina.

Two-photon excited fluorescence (TPEF) is a powerful technique that enables the examination of intrinsic retinal fluorophores involved in cellular metabolism and the visual cycle. Although previous intensity-based TPEF studies in non-human primates have successfully imaged several classes of retinal cells and elucidated aspects of both rod and cone photoreceptor function, fluorescence lifetime imaging (FLIM) of the retinal cells under light-dark visual cycle has yet to be fully exploited. Here we demonstrate a FLIM assay of photoreceptors and retinal pigment epithelium (RPE) that reveals key insights into retinal physiology and adaptation. We found that photoreceptor fluorescence lifetimes increase and decrease in sync with light and dark exposure, respectively. This is likely due to changes in all-trans-retinol and all-trans-retinal levels in the outer segments, mediated by phototransduction and visual cycle activity. During light exposure, RPE fluorescence lifetime was observed to increase steadily over time, as a result of all-trans-retinol accumulation during the visual cycle and decreasing metabolism caused by the lack of normal perfusion of the sample. Our system can measure the fluorescence lifetime of intrinsic retinal fluorophores on a cellular scale, revealing differences in lifetime between retinal cell classes under different conditions of light and dark exposure.

Apatinib combined with temozolomide in diffuse midline glioma: a novel and effective therapy.

PURPOSE: Diffuse midline glioma (DMG), H3 K27M-mutant is a type of diffuse high-grade glioma that occurs in the brain midline carrying an extremely poor prognosis under the best efforts of surgery, radiation, and other therapies. For better therapy, we explored the efficacy and toxicity of a novel therapy that combines apatinib and temozolomide in DMG. METHODS: A retrospective analysis of 32 patients with DMG who underwent apatinib plus temozolomide treatment was performed. Apatinib was given 500 mg in adults, 250 mg in pediatric patients once daily. Temozolomide was administered at 200 mg/m2/d according to the standard 5/28 days regimen. The main clinical data included basic information of patients, radiological and pathological characteristics of tumors, treatment, adverse reactions, prognosis. RESULTS: The objective response rate was 24.1%, and the disease control rate was 79.3%. The median PFS of all patients was 5.8 months, and median OS was 10.3 months. A total of 236 cycles of treatment were available for safety assessment and the toxicity of the combination therapy was relatively well tolerated. The most common grade 3 toxicities were myelosuppression including leukopenia (5.08%), neutropenia (4.24%), lymphopenia (2.12%), thrombocytopenia (1.69%) and anemia (1.27%). Grade 4 toxicities included neutropenia (2.12%), thrombocytopenia (2.12%) and proteinuria (1.69%). All the adverse events were relieved after symptomatic treatment or dose reduction. CONCLUSIONS: Apatinib plus temozolomide could be an effective regimen with manageable toxicities and favorable efficacy and may outperform temozolomide monotherapy, particularly in newly diagnosed adults with tumors located outside the pons. The novel therapy deserves further investigation in adult DMG patients.

ELM2-SANT Domain-Containing Scaffolding Protein 1 Regulates Differentiation and Maturation of Cardiomyocytes Derived From Human-Induced Pluripotent Stem Cells.

BACKGROUND: ELMSAN1 (ELM2-SANT domain-containing scaffolding protein 1) is a newly identified scaffolding protein of the MiDAC (mitotic deacetylase complex), playing a pivotal role in early embryonic development. Studies on Elmsan1 knockout mice showed that its absence results in embryo lethality and heart malformation. However, the precise function of ELMSAN1 in heart development and formation remains elusive. To study its potential role in cardiac lineage, we employed human-induced pluripotent stem cells (hiPSCs) to model early cardiogenesis and investigated the function of ELMSAN1. METHODS AND RESULTS: We generated ELMSAN1-deficient hiPSCs through knockdown and knockout techniques. During cardiac differentiation, ELMSAN1 depletion inhibited pluripotency deactivation, decreased the expression of cardiac-specific markers, and reduced differentiation efficiency. The impaired expression of genes associated with contractile sarcomere structure, calcium handling, and ion channels was also noted in ELMSAN1-deficient cardiomyocytes derived from hiPSCs. Additionally, through a series of structural and functional assessments, we found that ELMSAN1-null hiPSC cardiomyocytes are immature, exhibiting incomplete sarcomere Z-line structure, decreased calcium handling, and impaired electrophysiological properties. Of note, we found that the cardiac-specific role of ELMSAN1 is likely associated with histone H3K27 acetylation level. The transcriptome analysis provided additional insights, indicating maturation reduction with the energy metabolism switch and restored cell proliferation in ELMSAN1 knockout cardiomyocytes. CONCLUSIONS: In this study, we address the significance of the direct involvement of ELMSAN1 in the differentiation and maturation of hiPSC cardiomyocytes. We first report the impact of ELMSAN1 on multiple aspects of hiPSC cardiomyocyte generation, including cardiac differentiation, sarcomere formation, calcium handling, electrophysiological maturation, and proliferation.

Advances in immune regulation of the G protein-coupled estrogen receptor.

Estrogen and related receptors have been shown to have a significant impact on human development, reproduction, metabolism and immune regulation and to play a critical role in tumor development and treatment. Traditionally, the nuclear estrogen receptors (nERs) ERα and ERß have been thought to be involved in mediating the estrogenic effects. However, our group and others have previously demonstrated that the G protein-coupled estrogen receptor (GPER) is the third independent ER, and estrogen signaling mediated by GPER is known to play an important role in normal physiology and a variety of abnormal diseases. Interestingly, recent studies have progressively revealed GPER involvement in the maintenance of the normal immune system, abnormal immune diseases, and inflammatory lesions, which may be of significant clinical value primarily in the immunotherapy of tumors. In this article, we review current advances in GPER-related immunomodulators and provide a theoretical basis and potential clinical targets to ameliorate immune-related diseases and immunotherapy for tumors.