Suicidal ideation and suicide attempts among students aged 12 to 24 after the lifting of COVID-19 restrictions in China: prevalence and associated factors.

Objective: To investigate the prevalence and associated factors of suicidal ideation and suicide attempts among adolescent and young adults in China from December 14, 2022 to February 28, 2023, when COVID-19 restrictions were lifted. Methods: Students in middle and high schools and colleges and universities in the province of Sichuan, China were asked to complete on-line cross-sectional surveys. Information was collected about sociodemographics, experiences related to the COVID-19 pandemic, suicidal ideation and suicide attempts. Participants also filled out the Patient Health Questionnaire-9, the Generalized Anxiety Disorder-7 and the Social Support Rate Scale surveys. Factors associated with suicidal ideation or suicide attempts were explored using logistic regression. Results: Of the 82,873 respondents (aged 12 to 24 years), 21,292 (25.7%) reported having thought of suicide at least once in their lifetime, 10,382 (12.5%) reported having thought about suicide within the previous 12 months, and 1,123 (1.4%) reported having attempted it within the previous 12 months. Risk of lifetime suicidal ideation was higher among middle school students than among older students. Risk of suicidal ideation and risk of suicide attempts correlated directly with severity of symptoms of depression and anxiety, and inversely with level of social support. Greater risk of suicidal ideation and suicidal attempts was associated with: being female, living in an urban environment, attending a boarding school, currently being in love, having parents who divorced or remarried, having parents who exhibit non-authoritative parenting behavior, having higher family income, having been COVID-19 infected, having been quarantined for a long time, and being dissatisfied with one's education. Conclusions: Suicidal ideation and suicide attempts remain prevalent among young people in China. The potential associated factors identified in our study may be useful for targeting appropriate psychosocial interventions and developing mental health policies.

Glycyrrhetinic acid triggers a protective autophagy by inhibiting the JAK2/STAT3 pathway in cerebral ischemia/reperfusion injury.

Cerebral ischemia/reperfusion injury (CIRI) is a common feature of ischemic stroke leading to a poor prognosis. Effective treatments targeting I/R injury are still insufficient. The study aimed to investigate the mechanisms, by which glycyrrhizic acid (18ß-GA) in ameliorates CIRI. Our results showed that 18ß-GA significantly decreased the infarct volume, neurological deficit scores, and pathological changes in the brain tissue of rats after middle cerebral artery occlusion. Western blotting showed that 18ß-GA inhibited the expression levels of phosphorylated JAK2 and phosphorylated STAT3. Meanwhile, 18ß-GA increased LC3-II protein levels in a reperfusion duration-dependent manner, which was accompanied by an increase in the Bcl-2/Bax ratio. Inhibition of 18ß-GA-induced autophagy by 3-methyladenine (3-MA) enhanced apoptotic cell death. In addition, 18ß-GA inhibited the JAK2/STAT3 pathway, which was largely activated in response to oxygen-glucose deprivation/reoxygenation. However, the JAK2/STAT3 activator colivelin TFA abolished the inhibitory effect of 18ß-GA, suppressed autophagy, and significantly decreased the Bcl-2/Bax ratio. Taken together, these findings suggested that 18ß-GA pretreatment ameliorated CIRI partly by triggering a protective autophagy via the JAK2/STAT3 pathway. Therefore might be a potential drug candidate for treating ischemic stroke.

The auxin-responsive CsSPL9-CsGH3.4 module finely regulates auxin levels to suppress the development of adventitious roots in tea (Camellia sinensis).

The cutting technique is extensively used in tea breeding, with key emphasis on promoting the growth of adventitious roots (ARs). Despite its importance in tea cultivation, the mechanisms underlying AR development in tea remain unclear. In this study, we demonstrated the essential role of auxins in the initiation and progression of AR and established that the application of exogenous 1-naphthaleneacetic acid-enhanced AR formation in tissue-cultured seedlings and cuttings. Then, we found that the auxin-responsive transcription factor CsSPL9 acted as a negative regulator of AR development by reducing the levels of free indole-3-acetic acid (IAA) in tea plants. Furthermore, we identified CsGH3.4 as a downstream target of CsSPL9, which was activated by direct binding to its promoter. CsGH3.4 also inhibited AR development and maintained low levels of free IAA. Thus, these results revealed the inhibitory effect of the auxin-responsive CsSPL9-CsGH3.4 module on AR development by reducing free IAA levels in tea. These findings have significant theoretical and practical value for enhancing tea breeding practices.

Atypical Guillain-Barré syndrome with positive anti-sulfatide, anti-GT1b, and anti-GT1a antibodies: A case report.

BACKGROUND: The role of diverse antibodies in mediating peripheral nerve injury in Guillain-Barré syndrome (GBS) is becoming clearer, but positivity for multiple antibodies in one case is uncommon. To our knowledge, this is the first case involving GBS with positive anti-sulfatide, anti-GT1a, and anti-GT1b antibodies. CASE SUMMARY: A 20-year-old female patient was admitted to the hospital due to weakness of limbs for 5 d, and deterioration of the weakness and muscle aches for 1 d. The patient's limbs were weak, but the tendon reflexes in the part of the limbs were normal. There was no comorbid peripheral nociception or deep sensory dysfunction. She was diagnosed with GBS and was discharged after receiving intravenous human immunoglobulin pulse therapy. CONCLUSION: In this article, the clinical manifestations, neurophysiological examination, and auxiliary examination findings of a GBS patient positive for multiple antibodies were analyzed to improve the identification of the disease by clinical physicians at an early stage.

Efficacy and underlying mechanisms of three-circle post standing qigong on insomnia in college students: a four-arm, double-blind, randomized controlled trial protocol.

BACKGROUND: Insomnia is common in college students, but its impact on health and wellbeing is often neglected. Enhancing sleep quality through targeted interventions could improve overall health and reduce the risk of consequent co-morbidities and mental health problems. Qigong exercises have been shown to significantly improve sleep quality and relieve insomnia. Three-circle Post Standing (TCPS) can help integrate body, breath, and mind, a fundamental principle of Qigong that promotes holistic wellbeing. In this clinical trial, we aim to (1) evaluate the feasibility, safety, and therapeutic efficacy of administering TCPS to improve sleep quality and quality of life in college students with insomnia; (2) explore the neurophysiological mechanisms underlying the mind adjustments mediated by TCPS in insomnia; (3) investigate body and breath pathophysiology mediated by TCPS in insomnia; and (4) assess the long-term efficacy of TCPS in terms of sleep quality and quality of life. METHODS: This will be a prospective, parallel, four-arm, double-blind randomized controlled trial to investigate the effects and underlying mechanisms of TCPS on college students with insomnia. One hundred college students meeting diagnostic criteria for insomnia will be randomly assigned to receive either 14 weeks of standardized TCPS training (two weeks of centralized training followed by 12 weeks of supervised training) or sham-control Post Standing training. Efficacy outcomes including sleep quality, quality of life, neurophysiological assessments, plantar pressure, biomechanical balance, and physical measures will be collected at baseline, eight weeks (mid-point of supervised training), and 14 weeks (end of supervised training). Sleep quality and quality of life will also be evaluated during the four- and eight-week follow-up. DISCUSSION: This trial will be an important milestone in the development of new therapeutic approaches for insomnia and should be easily implementable by college students with insomnia. The neuro- and pathophysiological assessments will provide new insights into the mechanisms underlying TCPS. CLINICAL TRIAL REGISTRATION: This trial has been registered in the China Clinical Trials Registry (registration number: ChiCTR2400080763).

Regulation of IFP in solid tumours through acoustic pressure to enhance infiltration of nanoparticles of various sizes.

Numerous nanomedicines have been developed recently that can accumulate selectively in tumours due to the enhanced permeability and retention (EPR) effect. However, the high interstitial fluid pressure (IFP) in solid tumours limits the targeted delivery of nanomedicines. We were previously able to relieve intra-tumoural IFP by low-frequency non-focused ultrasound (LFNFU) through ultrasonic targeted microbubble destruction (UTMD), improving the targeted delivery of FITC-dextran. However, the accumulation of nanoparticles of different sizes and the optimal acoustic pressure were not evaluated. In this study, we synthesised Cy5.5-conjugated mesoporous silica nanoparticles (Cy5.5-MSNs) of different sizes using a one-pot method. The Cy5.5-MSNs exhibited excellent stability and biosafety regardless of size. MCF7 tumour-bearing mice were subjected to UTMD over a range of acoustic pressures (0.5, 0.8, 1.5 and 2.0 MPa), and injected intravenously with Cy5.5-MSNs. Blood perfusion, tumour IFP and intra-tumoural accumulation of Cy5.5-MSNs were analysed. Blood perfusion and IFP initially rose, and then declined, as acoustic pressure intensified. Furthermore, UTMD significantly enhanced the accumulation of differentially sized Cy5.5-MSNs in tumour tissues compared to that of the control group, and the increase was sevenfold higher at an acoustic pressure of 1.5 MPa. Taken together, UTMD enhanced the infiltration and accumulation of Cy5.5-MSNs of different sizes in solid tumours by reducing intra-tumour IFP.

Stable detection of diazinon residues in vegetables by an electrochemiluminescent aptasensor based on the in-situ production of H2O2 from dual-catalytic glucose.

Stable detection of diazinon (DZN) residues in vegetables is important for food safety. In this work, an electrochemiluminescence (ECL) aptasensor with dual-catalytic glucose in-situ production of H2O2 was constructed for the stable detection of DZN in vegetables. Firstly, MWCNTs@MB was prepared using π-π stacking interactions between methylene blue (MB) and multi-walled carbon nanotubes (MWCNTs) to enhance the loading of MB on an electrode and thus catalyze the generation of H2O2 from glucose. Secondly, Cu2O@AuNPs was formed by loading AuNPs on the surface of Cu2O through spontaneous reduction reaction, which improved the interfacial charge transfer, Cu2O nano-enzyme had glucose oxidase mimicking activity and could further catalyze the production of more H2O2 from glucose. MWCNTs@MB and Cu2O@AuNPs played a key role in the in-situ generation of co-reacting reagent H2O2, which solved the problem of unstable detection caused by the easy decomposition of the H2O2 solution added to the luminescence system. In addition, the aptamer was immobilized on the electrode surface by forming Au-S bonds with Cu2O@AuNPs. As a result, the ECL aptasensor performed good linearity in 1.00 pg mL-1-1.00 µg mL-1 and a low limit of detection (LOD) to 0.39 pg mL-1 (S/N = 3). This work provided an effective method for the accurate and stable detection of DZN residues in vegetables, which was of great significance in ensuring food safety and assessing the environmental risk of DZN.

A new coumarin and a new flavonoid from Ochrocarpus longifolius.

A new coumarin (1) and a new flavonoid (2) were isolated from the air-dried flower buds of Ochrocarpus longifolius, together with ten known compounds (3-12). The structures of two new compounds were established by 1D and 2D NMR and MS data. In addition, the new compound 2 showed significant proliferation inhibitory activity on Eca-109 and MGC-803 cells. The results of this study may enrich the diversity of compounds from O. longifolius and provide a basis for further research on its natural products and pharmacological activities.

Intra-thyroid esophageal duplication cyst: A case report.

BACKGROUND: Esophageal cysts are relatively rare in clinical practice, with most of the literature comprising case reports. Esophageal cysts protruding into the thyroid gland are easily misdiagnosed as thyroid tumors. No such cases have been reported so far. CASE SUMMARY: This article reports the case of a 31-year-old adult male diagnosed with thyroid nodules before admission. The patient underwent left thyroidectomy and isthmusectomy. During the surgery, esophageal cysts were identified in the esophageal muscle and thyroid glands. The pathology results confirmed a nodular goiter combined with esophageal cysts. Postoperatively, the patient developed a neck infection and underwent another operation and broad-spectrum antibiotic treatment for recovery. CONCLUSION: We report the first clinical case of an esophageal cyst located within the thyroid gland that was successfully treated surgically. Esophageal cyst located within the thyroid gland cause difficulties in diagnosis. In the present study, the contents of the esophageal cysts were calcified foci, and a small amount of fluid mixture, which were easily misdiagnosed as thyroid nodules and misled the surgical methods.

Expanded ROS Generation and Hypoxia Reversal: Excipient-free Self-assembled Nanotheranostics for Enhanced Cancer Photodynamic Immunotherapy.

The efficacy of photodynamic therapy (PDT)-related cancer therapies is significantly restricted by two irreconcilable obstacles, i.e., low reactive oxygen species (ROS) generation capability and hypoxia which constrains the immune response. Herein, this work develops a self-assembled clinical photosensitizer indocyanine green (ICG) and the HSP90 inhibitor 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) nanoparticles (ISDN) without any excipient. This work discovers that the hydrophobic interaction forces between ICG and 17-DMAG promote the photostability of ICG and its intersystem crossing (ISC) process, thereby improving the ROS quantum yield from 0.112 to 0.46. Augmented ROS generation enhances PDT efficacy and further enhances immunogenic cell death (ICD) effects. 17-DMAG inhibits the HSP90/hypoxia-inducible factor 1α (HIF-1α) axis to dramatically reverse the immunosuppressive tumor microenvironment caused by PDT-aggravated hypoxia. In a mouse model of pancreatic cancer, ISDN markedly improve cytotoxic T lymphocyte infiltration and MHC I and MHC II activation, demonstrating the superior ICD effects in situ tumor and the powerful systematic antitumor immunity generation, eventually achieving vigorous antitumor and recurrence resistance. This study proposes an unsophisticated and versatile strategy to significantly improve PDT efficacy for enhancing systemic antitumor immunity and potentially extending it to multiple cancers.

The regulation of intestinal flora on host's genes may play an essential role in the development of endometrial hyperplastic processes in yang deficiency individuals.

Yang-deficiency constitution (YADC) is linked to a higher vulnerability to various diseases, such as cold coagulation and blood stasis (CCBS) syndrome and infertility. Endometrial hyperplastic processes (EHPs) are a leading cause of infertility in women and are characterized by CCBS. However, it remains unclear whether YADC is related to the development of EHPs. METHODS: We recruited 202 EHPs patients including 147 with YADC (YEH group) and 55 with non-YADC (NYEH group). Fecal samples were collected from 8 YEH patients and 3 NYEH patients and analyzed using 16S rRNA V3-V4 sequencing for gut microbiota analysis. We obtained constitution survey data and a differential gut microbiota dataset from the literature for further analysis. Bioinformatics analysis was conducted using gut microbiota-related genes from public databases. RESULTS: YADC was significantly more prevalent in EHPs than non-YADC (P < 0.001), suggesting it as a potential risk factor for EHPs occurrence (ORpopulation survey = 13.471; ORhealthy women = 5.173). The YEH group had higher levels of inflammation, estrogen, and tamoxifen-related flora compared to NYEH and healthy YADC groups. There was an interaction between inflammation, estrogen, differential flora, and EHPs-related genes, particularly the TNF gene (related to inflammation) and the EGFR gene (related to estrogen), which may play a crucial role in EHPs development. CONCLUSION: YEH individuals exhibit significant changes in their gut microbiota compared to NYEH and healthy YADC. The interaction between specific microbiota and host genes is believed to play a critical role in the progression of EHPs.

Inhibition of CXCR4: A perspective on miracle fruit seed for Alzheimer's disease treatment.

Alzheimer's disease (AD) is the most prevalent type of dementia, and its causes are currently diverse and not fully understood. In a previous study, we discovered that short-term treatment with miracle fruit seed (MFS) had a therapeutic effect on AD model mice, however, the precise mechanism behind the effect remains unclear. In this research, we aimed to establish the efficacy and safety of long-term use of MFS in AD model mice. A variety of cytokines and chemokines have been implicated in the development of AD. Previous studies have validated a correlation between the expression levels of C-X-C chemokine receptor type 4 (CXCR4) and disease severity in AD. In this research, we observed an upregulation of CXCR4 expression in hippocampal tissues in the AD model group, which was then reversed after MFS treatment. Moreover, CXCR4 knockout led to improving cognitive function in AD model mice, and MFS showed the ability to regulate CXCR4 expression. Finally, our findings indicate that CXCR4 knockout and long-term MFS treatment produce comparable effects in treating AD model mice. In conclusion, this research demonstrates that therapeutic efficacy and safety of long-term use of MFS in AD model mice. MFS treatment and the subsequent reduction of CXCR4 expression exhibit a neuroprotective role in the brain, highlighting their potential as therapeutic targets for AD.

Comparative Study on the Immunogenicity and Efficacy of Different Post-exposure Intramuscular Rabies Vaccination Regimens in China.

Objective: This study aimed to compare the current Essen rabies post-exposure immunization schedule (0-3-7-14-28) in China and the simple 4-dose schedule (0-3-7-14) newly recommended by the World Health Organization in terms of their safety, efficacy, and protection. Methods: Mice were vaccinated according to different immunization schedules, and blood was collected for detection of rabies virus neutralizing antibodies (RVNAs) on days 14, 21, 28, 35, and 120 after the first immunization. Additionally, different groups of mice were injected with lethal doses of the CVS-11 virus on day 0, subjected to different rabies immunization schedules, and assessed for morbidity and death status. In a clinical trial, 185 rabies-exposed individuals were selected for post-exposure vaccination according to the Essen schedule, and blood was collected for RVNAs detection on days 28 and 42 after the first immunization. Results: A statistically significant difference in RVNAs between mice in the Essen and 0-3-7-14 schedule groups was observed on the 35th day ( P < 0.05). The groups 0-3-7-14, 0-3-7-21, and 0-3-7-28 showed no statistically significant difference ( P > 0.05) in RVNAs levels at any time point. The post-exposure immune protective test showed that the survival rate of mice in the control group was 20%, whereas that in the immunization groups was 40%. In the clinical trial, the RVNAs positive conversion rates on days 28 (14 days after 4 doses) and 42 (14 days after 5 doses) were both 100%, and no significant difference in RVNAs levels was observed ( P > 0.05). Conclusion: The simple 4-dose schedule can produce sufficient RVNAs levels, with no significant effect of a delayed fourth vaccine dose (14-28 d) on the immunization potential.

The Impact of Spironolactone Co-administration on Cyclosporin Initial Dosage Optimization for Pediatric Refractory Nephrotic Syndrome.

OBJECTIVES: Cyclosporin has been used for the treatment of pediatric refractory nephrotic syndrome (PRNS). However, the narrow therapeutic window and large pharmacokinetic variability make it difficult to individualize cyclosporin administration. Meanwhile, spironolactone has been reported to affect cyclosporin metabolism in PRNS patients. This study aims to explore the initial dosage optimization of cyclosporin in PRNS based on the impact of spironolactone co-administration. METHODS: Monte Carlo simulation based on a previously established cyclosporin population pharmacokinetic model for PRNS was used to design cyclosporin dosing regimen. RESULTS: In this study, the probability of drug concentration reaching the target and the convenience of times of administration were considered comprehensively. The optimal administration regimen in PRNS without spironolactone was 6, 5, 4 and 3 mg/kg cyclosporin split into two doses for the body weight of 5-8, 8-18, 18-46 and 46-70 kg, respectively. The optimal administration regimen in PRNS with spironolactone was 4, 3, 2 mg/kg cyclosporin split into two doses for body weight of 5-14, 14-65, and 65-70 kg, respectively. CONCLUSION: The cyclosporin dosing regimen for PRNS based on Monte Carlo simulation was systematically developed and the initial dosage optimization of cyclosporin in PRNS was recommended for the first time.

Meta-analysis of modified Sijunzi decoction for the treatment of chronic atrophic gastritis.

BACKGROUND: Qi deficiency in the spleen and stomach is considered to be the fundamental pathogenesis of chronic atrophic gastritis (CAG) in Traditional Chinese medicine. Spleen strengthening and Qi replenishment are the basic treatment principles. Sijunzi Decoction serves as the fundamental remedy for spleen notification and Qi replenishment. METHODS: The Cochrane Library, China National Knowledge Infrastructure China Biology Medicine disc, VIP, Wanfang Database, Web of Science, PubMed, and Embase were retrieved for related randomized controlled trials published from the inception of the databases to June 3, 2023. Literature screening and data extraction were executed by 2 independent investigators. The Cochrane Collaboration tool was leveraged to appraise the quality of included studies. Meta-analysis was implemented utilizing Stata 15. RESULTS: This analysis incorporated 32 studies with 2780 patients. The analysis results unveiled that compared to Western medicine treatment, modified Sijunzi Decoction significantly enhanced the clinical efficacy (relative risk [RR] = 1.241, 95% confidence interval [95% CI] = 1.199-1.285, P < .0001), lowered symptom scores (standardized mean difference [SMD] = -1.846, 95% CI = -2.160 to -1.532, P < .00001) and gastroscopic pathological scores (SMD = -1.122, 95% CI = -1.492 to -0.752, P < .00001), ameliorated quality of life (SMD = 4.294, 95% CI = 2.982-5.606, P < .00001), increased the Helicobacter pylori eradication rate (RR = 1.297, 95% CI = 1.035-1.625, P < .001), pepsinogen I levels (SMD = 2.615, 95% CI = 2.344-2.886, P < .00001), pepsinogen I/II ratio (SMD = 3.107, 95% CI = 2.811-3.403, P < .00001), and gastrin-17 levels (SMD = 1.004, 95% CI = 0.794-1.215, P < .00001), and reduced the incidence of adverse reactions (RR = 0.361, 95% CI = 0.235-0.556, P < .01) in individuals with CAG, with statistically significant discrepancies. CONCLUSION: Modified Sijunzi Decoction exhibited superior efficacy to conventional Western medicine in treating CAG. It was shown to improve the Helicobacter pylori eradication rate, reduce symptom scores, enhance quality of life, and improve pepsinogen-related indicators with a high safety profile.

Effects of tacrolimus on proteinuria in Chinese and Indian patients with idiopathic membranous nephropathy: the results of machine learning study.

PURPOSE: The present study aims to explore the effects of tacrolimus on proteinuria in patients with idiopathic membranous nephropathy (IMN) and recommend an appropriate dosage schedule via machine learning method. METHODS: The Emax model was constructed to analyze the effects of tacrolimus on proteinuria in patients with IMN. Data were mined from published literature and machine learning was built up with Emax model, among which the efficacy indicator was proteinuria change rates from baseline. 463 IMN patients were included for modeling, and tacrolimus therapeutic window concentrations were 4-10 ng/ml. RESULTS: In machine learning model, the Emax from tacrolimus effecting proteinuria in IMN patients was -72.7%, the ET50 was 0.43 months, and the time to achieving 25% Emax, 50% Emax, 75% Emax, and 80% (plateau) Emax of tacrolimus on proteinuria in patients with IMN were 0.15, 0.43, 1.29, and 1.72 months, respectively. CONCLUSION: For achieving better therapeutic effects from tacrolimus on proteinuria in patients with IMN, tacrolimus concentration range need to be maintained at 4-10 ng/ml for at least 1.72 months.

Multi-omics analysis reveals that linoleic acid metabolism is associated with variations of trained immunity induced by distinct BCG strains.

Trained immunity is one of the mechanisms by which BCG vaccination confers persistent nonspecific protection against diverse diseases. Genomic differences between the different BCG vaccine strains that are in global use could result in variable protection against tuberculosis and therapeutic effects on bladder cancer. In this study, we found that four representative BCG strains (BCG-Russia, BCG-Sweden, BCG-China, and BCG-Pasteur) covering all four genetic clusters differed in their ability to induce trained immunity and nonspecific protection. The trained immunity induced by BCG was associated with the Akt-mTOR-HIF1α axis, glycolysis, and NOD-like receptor signaling pathway. Multi-omics analysis (epigenomics, transcriptomics, and metabolomics) showed that linoleic acid metabolism was correlated with the trained immunity-inducing capacity of different BCG strains. Linoleic acid participated in the induction of trained immunity and could act as adjuvants to enhance BCG-induced trained immunity, revealing a trained immunity-inducing signaling pathway that could be used in the adjuvant development.

Pharmacological suppression of HHLA2 glycosylation restores anti-tumor immunity in colorectal cancer.

Immunotherapy aimed at inhibiting the negative co-stimulatory molecule programmed cell death-ligand 1 (PD-L1) has limited effectiveness, with clinical response rates remaining below 10%-15%. Therefore, new immune checkpoints need to be explored. Our study focused on human endogenous retrovirus H long terminal repeat-associating protein 2 (HHLA2), a highly glycosylated member of the B7 family that is widely expressed in colorectal cancer. HHLA2 expression negatively correlates with the prognosis of colorectal cancer. Glycosylation of HHLA2, which is regulated by the glycosyltransferase STT3 oligosaccharyltransferase complex catalytic subunit A (STT3A), is crucial for protein stability and expression in cell membranes. Additionally, the binding of HHLA2 to the receptors killer cell immunoglobulin-like receptor, three immunoglobulin domains and long cytoplasmic tail 3 (KIR3DL3) and transmembrane and immunoglobulin (Ig) domain containing 2 (TMIGD2) is dependent on N-glycosylation. Moreover, N-glycosylation of HHLA2 promotes immune evasion in colorectal cancer by suppressing the immune response of NK cells. Notably, the STT3A inhibitor NGI-1 enhances the anti-tumor immune response of NK cells. Our findings provide new insights and a molecular basis for targeting HHLA2 in immunotherapy for colorectal cancer.