Understanding the Transepithelial Transport and Transbilayer Diffusion of the Antihypertensive Peptide Asn-Cys-Trp: Insights from Caco-2 Cell Monolayers and the DPPC Model Membrane.

Understanding the transport mechanism of the peptide Asn-Cys-Trp (NCW) is crucial to improving its intestinal absorption and bioavailability. This study investigated the absorption of NCW through Caco-2 cell monolayers and its interaction with the DPPC bilayers. Results revealed that after a 3 h incubation, the Papp (AP-BL) and Papp (BL-AP) values of NCW at a concentration of 5 mmol/L were (22.24 ± 4.52) × 10-7 and (6.63 ± 2.31) × 10-7 cm/s, respectively, with the transport rates of 1.59 ± 0.32 and 0.62 ± 0.20%, indicating its moderate absorption. NCW was found to be transported via PepT1 and paracellular transport pathways, as evidenced by the significant impact of Gly-Pro and cytochalasin D on the Papp values. Moreover, NCW upregulated ZO-1 mRNA expression. Further investigation of the ZO-1-mediated interaction between NCW and tight junction proteins will contribute to a better understanding of the paracellular transport mechanism of NCW. The interaction between NCW and the DPPC bilayers was predominantly driven by entropy. NCW permeated the bilayers through electrostatic, hydrogen bonding, and hydrophobic interactions, resulting in increased fluidity, flexibility, and disorder as well as phase transition and phase separation of the bilayers.

Study transport of hesperidin based on the DPPC lipid model and the BSA transport model.

Hesperidin (HE), a significant flavonoid polyphenolic compound present in citrus plants, exhibits diverse pharmacological effects. Considering the crucial involvement of biological membranes and transporter proteins in the transportation and biological processes of HE, it becomes essential to comprehend the potential mechanisms through which HE interacts with membranes and transporter proteins. In order to simulate the process of active molecule transport, a cell membrane model consisting of 1,2-dipalmitoyl-n-glycero-3-phosphatidylcholine (DPPC) and a transporter protein model of bovine serum albumin (BSA) were employed for investigation. The present study aimed to investigate the mechanism of action of hesperidin (HE) in DPPC and BSA using fluorescence quenching, Fourier transform infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC). The localization and interaction of HE within liposomes were also elucidated. Furthermore, the binding of BSA and HE was analyzed through UV/Vis absorption spectroscopy, fluorescence spectroscopy, infrared spectroscopy, and computational biology techniques. Computational biology analysis revealed that the binding between HE and BSA primarily occurred via hydrogen bonding and hydrophobic interactions. This study aimed to investigate the role and mechanism of HE in the DPPC cell membrane model and the BSA transporter protein model, thereby offering novel insights into the action of HE in DPPC and BSA.

Anthropogenic forcing has increased the risk of longer-traveling and slower-moving large contiguous heatwaves.

Heatwaves are consecutive hot days with devastating impacts on human health and the environment. These events may evolve across both space and time, characterizing a spatiotemporally contiguous propagation pattern that has not been fully understood. Here, we track the spatiotemporally contiguous heatwaves in both reanalysis datasets and model simulations and examine their moving patterns (i.e., moving distance, speed, and direction) in different continents and periods. Substantial changes in contiguous heatwaves have been identified from 1979 to 2020, with longer persistence, longer traveling distance, and slower propagation. These changes have been amplified since 1997, probably due to the weakening of eddy kinetic energy, zonal wind, and anthropogenic forcing. The results suggest that longer-lived, longer-traveling, and slower-moving contiguous heatwaves will cause more devastating impacts on human health and the environment in the future if greenhouse gas emissions keep rising and no effective measures are taken immediately. Our findings provide important implications for the adaption and mitigation of globally connected extreme heatwaves.

Differential genetic mutations and immune cell infiltration in high- and low-risk STAD: Implications for prognosis and immunotherapy efficacy.

This study investigates genetic mutations and immune cell dynamics in stomach adenocarcinoma (STAD), focusing on identifying prognostic markers and therapeutic targets. Analysis of TCGA-STAD samples revealed C > A as the most common single nucleotide variant (SNV) in both high and low-risk groups. Key mutated driver genes included TTN, TP53 and MUC16, with frame-shift mutations more prevalent in the low-risk group and missense mutations in the high-risk group. Interaction analysis of hub genes such as C1QA and CD68 showed significant correlations, impacting immune cell infiltration patterns. Using ssGSEA, we found higher immune cell infiltration (B cells, CD4+ T cells, CD8+ T cells, DC cells, NK cells) in the high-risk group, correlated with increased risk scores. xCell algorithm results indicated distinct immune infiltration levels between the groups. The study's risk scoring model proved effective in prognosis prediction and immunotherapy efficacy assessment. Key molecules like CD28, CD27 and SLAMF7 correlated significantly with risk scores, suggesting potential targets for high-risk STAD patients. Drug sensitivity analysis showed a negative correlation between risk scores and sensitivity to certain treatments, indicating potential therapeutic options for high-risk STAD patients. We also validated the carcinogenic role of RPL14 in gastric cancer through phenotypic experiments, demonstrating its influence on cancer cell proliferation, invasion and migration. Overall, this research provides crucial insights into the genetic and immune aspects of STAD, highlighting the importance of a risk scoring model for personalized treatment strategies and clinical decision-making in gastric cancer management.

The Effect of Bullying Victimization on Adolescent Non-Suicidal Self-Injury: The Mediating Roles of Alexithymia and Self-Esteem.

Background & Aim: Non-suicidal self-injury (NSSI) in adolescents is a serious public health issue influenced by the interaction of multiple factors. The purpose of this study was to investigate the multiple mediating roles of alexithymia and self-esteem in the association between bullying victimization and NSSI in a sample of Chinese adolescents. Methods: A survey of 1299 adolescents from two public middle schools in Henan Province, China, was undertaken. Data were collected using the Chinese version of the Delaware bullying victimization scale-student (DBVS-S), the Toronto Alexithymia-20 Scale (TAS-20-C), the Rosenberg self-esteem scale (RSES), and the adolescent self-injury questionnaire. Besides, we performed a structural equation modeling (SEM) with latent variables using AMOS 26.0 to examine the relationship between variables and the mediating effects. Results: The SEM analysis found that not only can bullying victimization directly impact NSSI, but that alexithymia and self-esteem have a chain mediating effect in the association between bullying victimization and NSSI. This mediating effect contributed 22.47% to the total effect. Conclusion: These findings validate bullying victimization, alexithymia, and low self-esteem are important variables that affect NSSI among Chinese adolescents. Educators need to implement some prevention and intervention strategies to ameliorate the campus atmosphere and adolescents' mental health aimed at avoiding NSSI behavior in adolescence.

The Relationship Between Illness Uncertainty and Social Support Among Cancer Patients: A Meta-analysis.

BACKGROUND: As a common psychological problem in cancer patients, illness uncertainty has attracted wide attention from scholars. Some studies have pointed out that the level of social support may affect illness uncertainty in patients with cancer, but the results of these studies remain controversial. OBJECTIVE: The aim of this study was to evaluate the correlation between illness uncertainty and social support in patients with cancer using meta-analysis. METHODS: PubMed, Web of Science, EMBASE, EBSCO, Cochrane Library, China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, and VIP Citation Database were searched for articles published up to 2022. The screening of the literature, data extraction, and quality assessment of the included studies were performed independently by 2 researchers. Stata 17.0 software was used to analyze the overall and moderation effects. RESULTS: Notably, 41 studies involving 5403 patients were included. The results showed that the illness uncertainty of adults with cancer was moderately negatively correlated with social support (r = -0.33). Country, publication year, cancer type, and instrument used to measure social support moderated the association between illness uncertainty and social support. CONCLUSION: Improving the level of social support can reduce illness uncertainty experienced by adults with cancer to a certain extent. IMPLICATIONS FOR PRACTICE: This review provides a clear direction for implementing precise interventions to reduce illness uncertainty among adults with cancer. Furthermore, patients with cancer with high morbidity and mortality rates deserve greater attention from healthcare personnel and family caregivers.

High-Z elements dominated bismuth-based heterojunction nano-semiconductor for radiotherapy-enhanced sonodynamic breast cancer therapy.

Ultrasound and X-rays possess remarkable tissue penetration capabilities, making them promising candidates for cancer therapy. Sonodynamic therapy, which utilizes ultrasound excitation, offers a safer alternative to radiotherapy and can be combined with X-rays to mitigate the adverse effects on normal tissues. In this study, we developed a bismuth-based heterostructure semiconductor (BFIP) to enhance the efficacy of radiotherapy and sonodynamic therapy in treating breast cancer. The semiconductor is fabricated through a two-step process involving the synthesis of porous spherical bismuth fluoride and partially reduced to bismuth oxyiodide. Then, followed by surface modification with amphiphilic polyethylene glycol, BFIP is fabricated. Incorporating heavy atoms in the BFIP enhances radiosensitivity. The BFIP exhibits superior carrier separation efficiency compared to bismuth fluoride, generating a substantial quantity of reactive oxygen species upon ultrasound stimulation. Moreover, the BFIP effectively depletes glutathione through coordination and hole-mediated oxidation pathways, disrupting the tumor microenvironment and inducing oxidative stress. Encouraging results are acquired in both in vitro cell and in vivo tumor models. Our study provides a de-risking strategy by utilizing ultrasound as a partial substitute for X-rays in treating deep-seated tumors, offering a viable research direction for constructing a unified nanoplatform.

Marine Bioactive Peptides: Anti-Photoaging Mechanisms and Potential Skin Protective Effects.

Skin photoaging, resulting from prolonged exposure to ultraviolet radiation, is a form of exogenous aging that not only impacts the aesthetic aspect of the skin but also exhibits a strong correlation with the onset of skin cancer. Nonetheless, the safety profile of non-natural anti-photoaging medications and the underlying physiological alterations during the process of photoaging remain inadequately elucidated. Consequently, there exists a pressing necessity to devise more secure interventions involving anti-photoaging drugs. Multiple studies have demonstrated the noteworthy significance of marine biomolecules in addressing safety concerns related to anti-photoaging and safeguarding the skin. Notably, bioactive peptides have gained considerable attention in anti-photoaging research due to their capacity to mitigate the physiological alterations associated with photoaging, including oxidative stress; inflammatory response; the abnormal expression of matrix metalloproteinase, hyaluronidase, and elastase; and excessive melanin synthesis. This review provides a systematic description of the research progress on the anti-photoaging and skin protection mechanism of marine bioactive peptides. The focus is on the utilization of marine bioactive peptides as anti-photoaging agents, aiming to offer theoretical references for the development of novel anti-photoaging drugs and methodologies. Additionally, the future prospects of anti-aging drugs are discussed, providing an initial reference for further research in this field.

The relationship between childhood trauma and internet addiction in adolescents: A meta-analysis.

Objective: Many studies have explored the relationship between childhood trauma and internet addiction from different theoretical perspectives; however, the results have been inconsistent. The purpose of this meta-analysis was to examine the relationship between childhood trauma and internet addiction. Methods: The PubMed, Web of Science, Embase, CNKI, Wanfang and VIP electronic databases were searched to identify studies examining the correlation between childhood trauma and adolescent internet addiction. The databases were searched from inception to December 31, 2022. Two researchers independently screened the literature, extracted the data, and evaluated the risk of bias of the included studies. Then, Stata 17.0 software was used to perform meta-analysis. Results: This study was registered on PROSPERO (CRD42023388699). A total of 19 studies involving 21,398 adolescents were included in this meta-analysis. The random effects model was used for pooled analysis, and the results revealed a strong positive association between childhood trauma and internet addiction (r = 0.395, 95% CI [0.345, 0.442]). The relationship between childhood trauma and internet addiction was moderated by sample size, survey area, and internet addiction measurement tools. There were significant differences between the associations based on the various child trauma measurement tools and study quality scores. However, interstudy heterogeneity was not significantly affected by study year, sample source, or participant age. Conclusion: Internet addiction is positively correlated with childhood trauma. Therefore, it is extremely important for parents to provide a good growth environment during childhood to enhance the physical and mental development of adolescents. A warm family atmosphere helps individuals develop a healthy personality, thereby reducing or preventing the occurrence of internet addiction. Due to the limited number and low quality of the included studies, the above conclusions need to be verified by additional high-quality studies.

Novel Targets and Potential Mechanisms of Mizuhopecten yessoensis-Derived Tripeptide NCW as Antihypertensive Peptides.

SCOPE: Mizuhopecten yessoensis-derived tripeptide Asn-Cys-Trp (NCW) exhibits a potent antihypertensive effect in vivo. However, a lack of knowledge of the antihypertensive mechanism of tripeptide NCW limits its application for functional foods industrialization. The purpose of this study is to elucidate the corresponding targets and mechanisms of tripeptide NCW in hypertension regulation. METHODS AND RESULTS: Administration of tripeptide NCW for 3 weeks, the blood pressure of spontaneously hypertensive rats (SHRs) is significantly decreased. After sacrifice, the serum sample is analyzed using tandem mass tag (TMT)-based liquid chromatography with tandem mass spectrometry to identify differentially expressed proteins. The proteomic analysis indicates that tripeptide NCW administration alters serum protein profiles in SHR rats, significantly upregulating 106 proteins and downregulating 30 proteins. These proteins enhance the glycolysis, glucose, and TCA cycle, improve amino metabolism, trigger the cAMP/PKA, cGMP/PKG, PI3K/AKT, and AMPK signal pathways, and inhibit Ras-regulated JNK activation, TGF-ß/MAPK, and TGF-ß/ RhoA/ROCK pathways. CONCLUSION: Tripeptide NCW supplementation is demonstrated to regulate signal pathways involved in the control of blood pressure and regulate the energy and amino acids metabolic processes in serum, providing important insights into the protective effects of tripeptide NCW on hypertension.

Fabrication and characterisation of collagen/pullulan ultra-thin fibers by electrospinning.

Collagen electrospun fibers are promising materials for food packaging and tissue engineering. The conventional electrospinning of collagen, however, is usually carried out by dissolving it in organic reagents, which are toxic. In this study, collagen/pullulan (COL/PUL) ultra-thin fibers were prepared by electrospinning using acetic acid as a solvent. Compared to the conventional preparation method, the proposed method is safe and does not produce toxic solvent residues. The introduction of PUL increased the degree of molecular entanglement in the solution, so the viscosity of the COL/PUL electrospun solution increased from 0.50 ± 0.01 Pa∙s to 4.40 ± 0.08 Pa∙s, and the electrical conductivity decreased from 1954.00 ± 1.00 mS/cm to 1372.33 ± 0.58 mS/cm. Scanning electron microscopy analysis confirmed that PUL improved the spinnability of COL, and smooth, defect-free COL/PUL ultra-thin fibers with diameters of 215.32 ± 40.56 nm and 240.97 ± 53.93 nm were successfully prepared at a viscosity of greater than 1.18 Pa∙s. As the proportion of PUL increased, intramolecular hydrogen bonds became the dominant interaction between COL and PUL. The intermolecular hydrogen bonding content decreased from 52.05 % to 36.45 %, and the intramolecular hydrogen bonding content increased from 46.11 % to 62.95 %. The COL was gradually unfolded, the content of α-helices decreased from 33.57 % to 25.91 % and the random coils increased from 34.22 % to 40.09 %. More than 36 % of the triple helix fraction of COL was retained by the COL/PUL ultra-thin fibers, whereas only 16 % of the triple helix fraction of COL was retained by the COL nanofibers prepared with 2.2.2-trifluoroethanol. These results could serve as a reference for the development of green food COL-based fibers.

Correlates of death anxiety for patients with cancer: A systematic review and meta-analysis.

OBJECTIVE: A systematic review and meta-analysis was performed to identify the factors related to cancer death anxiety based on available evidence. DESIGN: This systematic review and meta-analysis followed the PRISMA 2020 guidelines. METHODS: Seven databases were searched to identify studies on the relationships of cancer death anxiety with demographic characteristics, disease factors and psychosocial factors from inception to May 2023. The Agency for Medical Research and Quality (AHRQ) scale was used to evaluate the quality of the included studies. After two researchers independently completed the literature search, data extraction and quality evaluation, meta-analysis was conducted by using RevMan5.3 and Stata 17.0 software. RESULTS: In total, 52 studies were included in this review. The results revealed that there were positive correlations of death anxiety with female sex, the symptom burden, anxiety levels, depression levels, fear of recurrence, attachment avoidance, psychological distress, resignation and confrontation coping. Death anxiety was negatively correlated with age, education level, ability to perform daily activities, self-esteem, spiritual well-being, sense of meaning in life, resilience, quality of life, social support and religious beliefs. CONCLUSIONS: Our results can inform the design of interventions to address death anxiety and improve the overall quality of life of cancer patients. Healthcare professionals should promptly identify and focus on death anxiety in high-risk populations of cancer patients. RELEVANCE TO CLINICAL PRACTICE: Cancer patients commonly experience death anxiety, and this anxiety has a nonnegligible impact on patients' mental health and overall quality of life. This study can inform the development of interventions by clinical healthcare professionals. NO PATIENT OR PUBLIC CONTRIBUTION: This was a meta-analysis based on data from previous studies.

The role of alternative polyadenylation in epithelial-mesenchymal transition of non-small cell lung cancer.

The metastatic non-small cell lung cancer (NSCLC) is one of the cancers with high incidence, poor survival, and limited treatment. Epithelial-mesenchymal transition (EMT) is the first step by which an early tumor converts to an invasive one. Studying the underlying mechanisms of EMT can help the understanding of cancer metastasis and improve the treatment. In this study, 1013 NSCLC patients and 123 NSCLC cell lines are deeply analyzed for the potential roles of alternative polyadenylation (APA) in the EMT process. A trend of shorter 3'-UTRs (three prime untranslated region) is discovered in the mesenchymal samples. The identification of EMT-related APA events highlights the proximal poly(A) selection of CARM1. It is a pathological biomarker of mesenchymal tumor and cancer metastasis through losing miRNA binding to upregulate the EMT inducer of CARM1 and releasing miRNAs to downregulate the EMT inhibitor of RBM47. The crucial role of this APA event in EMT also guides its effect on drug responses. The patients with shorter 3'-UTR of CARM1 are more benefit from chemotherapy drugs, especially cisplatin. A stratification of NSCLC patients based on this APA event is useful for chemotherapy design in future clinics.

[A new allo-aromadendrane sesquiterpene from Dendrobium nobile].

To study the chemical constituents in the non-alkaloid part of stems of Dendrobium nobile. The macroporous adsorption resin, MCI, silica gel, RP-C_(18), and Sephadex LH-20 gel, preparative thin layer chromatography, and preparative high-performance liquid chromatography(HPLC) were used to isolate and purify the compounds. The structures of the compound were determined according to the spectra data, physicochemical properties, and relevant references. A total of 8 compounds were isolated from D. nobile, which were soltorvum F(1), p-hydroxyphenylpropionic acid(2), vanillic acid(3), p-hydroxybenzoic acid(4), N-trans-cinnamic acid acyl-p-hydroxybenzene ethylamine(5),(+)-(1R,2S,3R,4S,5R,6S,9R)-2,11,12-trihydroxypicrotoxane-3(15)-lactone(6), dendronobilin H(7), soltorvum E(8). Compound 1 was a novel compound, named as soltorvum F. Compound 8 was isolated from Dendrobium species for the first time.

Causal associations between female reproductive behaviors and psychiatric disorders: a lifecourse Mendelian randomization study.

BACKGROUND: The timings of reproductive life events have been examined to be associated with various psychiatric disorders. However, studies have not considered the causal pathways from reproductive behaviors to different psychiatric disorders. This study aimed to investigate the nature of the relationships between five reproductive behaviors and twelve psychiatric disorders. METHODS: Firstly, we calculated genetic correlations between reproductive factors and psychiatric disorders. Then two-sample Mendelian randomization (MR) was conducted to estimate the causal associations among five reproductive behaviors, and these reproductive behaviors on twelve psychiatric disorders, using genome-wide association study (GWAS) summary data from genetic consortia. Multivariable MR was then applied to evaluate the direct effect of reproductive behaviors on these psychiatric disorders whilst accounting for other reproductive factors at different life periods. RESULTS: Univariable MR analyses provide evidence that age at menarche, age at first sexual intercourse and age at first birth have effects on one (depression), seven (anxiety disorder, ADHD, bipolar disorder, bipolar disorder II, depression, PTSD and schizophrenia) and three psychiatric disorders (ADHD, depression and PTSD) (based on p<7.14×10-4), respectively. However, after performing multivariable MR, only age at first sexual intercourse has direct effects on five psychiatric disorders (Depression, Attention deficit or hyperactivity disorder, Bipolar disorder, Posttraumatic stress disorder and schizophrenia) when accounting for other reproductive behaviors with significant effects in univariable analyses. CONCLUSION: Our findings suggest that reproductive behaviors predominantly exert their detrimental effects on psychiatric disorders and age at first sexual intercourse has direct effects on psychiatric disorders.

A daily high-resolution (1 km) human thermal index collection over the North China Plain from 2003 to 2020.

Human-perceived temperature (HPT) describes the joint effects of multiple climatic factors such as temperature and humidity. Extreme HPT events may reduce labor capacity and cause thermal discomfort and even mortality. These events are becoming more frequent and more intense under global warming, posing severe threats to human and natural systems worldwide, particularly in populated areas with intensive human activities, e.g., the North China Plain (NCP). Therefore, a fine-scale HPT dataset in both spatial and temporal dimensions is urgently needed. Here we construct a daily high-resolution (~1 km) human thermal index collection over NCP from 2003 to 2020 (HiTIC-NCP). This dataset contains 12 HPT indices and has high accuracy with averaged determination coefficient, mean absolute error, and root mean squared error of 0.987, 0.970 °C, and 1.292 °C, respectively. Moreover, it exhibits high spatiotemporal consistency with ground-level observations. The dataset provides a reference for human thermal environment and could facilitate studies such as natural hazards, regional climate change, and urban planning.

Selenium-integrated conjugated oligomer nanoparticles with high photothermal conversion efficiency for NIR-II imaging-guided cancer phototheranostics in vivo.

Second near-infrared (NIR-II) fluorescence imaging in the range of 1000-1700 nm has great prospects for in vivo imaging and theranostics monitoring. At present, few NIR-II probes with theranostics properties have been developed, especially the high-performance organic theranostics material remains underexploited. Herein, we demonstrate a selenium (Se)-tailoring method to develop high-efficient NIR-II imaging-guided material for in vivo cancer phototheranostics. Via Se-tailoring strategy, conjugated oligomer TPSe-based nanoparticles (TPSe NPs) achieve bright NIR-II emission up to 1400 nm and exhibit a relatively high photothermal conversion efficiency of 60% with good stability. Moreover, the TPSe NPs demonstrate their photothermal ablation of cancer cells in vitro and tumor in vivo with the guidance of NIR-II imaging. It is worth noting that the TPSe NPs have good biocompatibility without obvious side effects. Thus, this work provides new insight into the development of NIR-II theranostics agents.

The impact of the Hedgehog signal pathway on the tumor immune microenvironment of gastric adenocarcinoma by integrated analysis of scRNA-seq and RNA-seq datasets.

The Hedgehog signaling is a highly conserved pathway to regulate cell growth and proliferation, and plays an essential role in stomach adenocarcinoma (STAD) and other cancer types. However, previous studies were primarily conducted in terms of mRNA or vitro cell culture. It would be more convincing to integrate single-cell RNA sequencing (scRNA-seq) data because it is a more precise approach for genomic research. The expression profile, genetic alteration, and activity of the Hedgehog signaling pathway were investigated in both scRNA-seq and RNA-seq datasets of STAD. Communications between cancer cells and fibroblasts were determined by the cell-chat algorithm, and the Hedgehog-related gene signature was constructed to predict the survival of STAD. Patients were categorized into high- and low-risk groups according to the median of the signature. Further analysis explored the difference in survival outcome, tumor immune microenvironment (TIME), and drug sensitivity between the two groups, aiming to guide the use of chemotherapy and immunotherapy in STAD patients. Hedgehog signal pathway was over-activated in STAD. GAS1, GLI1, and SCEBU2 were recognized as hub genes in the prognostic signature of STAD, and served as robust risk factors to induce a poor survival outcome. Patients in the high-risk group demonstrated an exhausted TIME pattern, with rather low sensitivity toward molecular-targeted drugs. This study depicted the influence of the Hedgehog pathway on the survival outcome, TIME, and drug sensitivity of STAD, and provides novel insights for the treatment of STAD.

The relationship between stigma and psychological distress among people with diabetes: a meta-analysis.

BACKGROUND & AIMS: Diabetes may perceive or experience varying degrees of stigma and psychological distress. The association between diabetes-related stigma and psychological distress has been examined in many studies, but no research has used a quantitative synthesis method to investigate the severity of this association and the moderators of the relationship. Thus, we conducted a meta-analysis to quantitatively integrate previous findings to identify the magnitude of the association between stigma and psychological distress among people with diabetes. REVIEW METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, we systematically searched four English academic databases (PubMed, Embase, Web of Science, and PsycINFO) and three Chinese databases (China National Knowledge Infrastructure [CNKI], WANFANG Data, China Science and Technology Journal Database [VIP]). The databases were searched from the inception of each database to the end of March 2023. The pooled correlation coefficient of the association between stigma and psychological distress among people with diabetes was calculated by a random effects model using Stata software (version 17.0), and several moderators that impacted this relationship were identified. RESULTS: Eligible studies (N = 19) with a total of 12,777 participants were analysed. The pooled correlation was high between diabetes-related stigma and psychological distress (r = 0.50, 95% CI: [0.43-0.57]). Moreover, the association was moderated by the diabetes stigma measurement tools and diabetes distress measurement tools used. However, the relationship was not moderated by type of diabetes, age, gender, geographical location, or type of stigma. CONCLUSIONS: The results of the meta-analysis showed that stigma is strongly related to psychological distress among people with diabetes. Longitudinal or experimental research should be expanded in the future to further identify the causal pathways in the relationship between diabetes stigma and diabetes distress.