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Background. Observational researches reported the underlying correlation of plasma myeloperoxidase (MPO) concentration with respiratory tract infections (RTIs), but their causality remained unclear. Here, we examined the cause–effect relation between plasma MPO levels and RTIs. Materials and Methods. Datasets of plasma MPO levels were from the Folkersen et al. study (n = 21,758) and INTERVAL study (n = 3,301). Summarized data for upper respiratory tract infection (URTI) (2,795 cases and 483,689 controls) and lower respiratory tract infection (LRTI) in the intensive care unit (ICU) (585 cases and 430,780 controls) were from the UK Biobank database. The primary method for Mendelian randomization (MR) analysis was the inverse variance weighted approach, with MR-Egger and weighted median methods as supplements. Cochrane's Q test, MR-Egger intercept test, MR pleiotropy residual sum and outliers global test, funnel plots, and leave-one-out analysis were used for sensitivity analysis. Results. We found that plasma MPO levels were positively associated with URTI (odds ratio (OR) = 1.135; 95% confidence interval (CI) = 1.011–1.274; P = 0.032) and LRTI (ICU) (OR = 1.323; 95% CI = 1.006–1.739; P = 0.045). The consistent impact direction is shown when additional plasma MPO level genome-wide association study datasets are used (URTI: OR = 1.158; 95% CI = 1.072–1.251; P < 0.001 ; LRTI (ICU): OR = 1.216; 95% CI = 1.020–1.450; P = 0.030). There was no evidence of a causal effect of URTI and LRTI (ICU) on plasma MPO concentration in the reverse analysis (P > 0.050). The sensitivity analysis revealed no violations of MR presumptions. Conclusions. Plasma MPO levels may causally affect the risks of URTI and LRTI (ICU). In contrast, the causal role of URTI and LRTI (ICU) on plasma MPO concentration was not supported in our MR analysis. Further studies are needed to identify the relationship between RTIs and plasma MPO levels. [ABSTRACT FROM AUTHOR]

Recent studies have revealed that the influence of diurnal temperature on spring phenology is asymmetric, and the faster night‐time warming in the Northern Hemisphere (NH) has a complex impact on spring phenology. Our understanding from the sensitivity of the start of the growing season (SOS) to daytime (ST_daytime) and night‐time temperatures (ST_night‐time) has urgently needs to be improved. In this study, the SOS sensitivity to diurnal temperature in the middle and high latitudes of the NH (>30°N) from 1982 to 2015 is estimated. The results indicate that although SOS showed stronger sensitivity to daytime than night‐time temperature in most parts of the study areas, the influence of daytime temperature on SOS is decreasing, while the influence of night‐time temperature on SOS is increasing. The variations in ST_daytime and ST_night‐time along the latitude gradient were significantly correlated with the warming rate of the preseason diurnal temperature (p <.01). The SOS between 40°N and 70°N was more sensitive to daytime temperature, while ST_night‐time was higher than ST_daytime at other latitudes due to topography and rapid night‐time warming. On the altitude gradient, the SOS was more sensitive to daytime temperature in areas below 800 and 2,000–4,000 m. ST_night‐time exceeded ST_daytime at other altitudes owing to night‐time warming relief of the severe restrictions on phenological processes and the reduction in frost risk. To reach a comprehensive characterization of the interaction between vegetation and climate systems, the current study suggests more investigation on the response of SOS to diurnal temperature on large scales. [ABSTRACT FROM AUTHOR]

Mapping flash flood susceptibility is effective for mitigating the negative impacts of flash floods. However, a variety of conditioning factors have been used to generate susceptibility maps in various studies. In this study, we proposed combining logistic regression (LR) and random forest (RF) models with embedded feature selection (EFS) to filter specific feature sets for the two models and map flash flood susceptibility in the mainstream basin of the Songhua River. According to the EFS results, the optimized feature sets included 32 and 28 features for the LR and RF models, respectively, and the composition of the two optimal feature sets was similar and distinct. Overall, the relevant vegetation cover and river features exhibit relatively high effects overall for flash floods in the study area. The LR and RF models provided accurate and reliable flash flood susceptibility maps (FFSMs). The RF model (accuracy = 0.8834, area under the curve (AUC) = 0.9486) provided a better prediction capacity than the LR model (accuracy = 0.8634, AUC = 0.9277). Flash flood-prone areas are mainly distributed in the south and southwest and areas close to rivers. The results obtained in this study is useful for flash flood prevention and control projects. [ABSTRACT FROM AUTHOR]

Industrially, NH3 production mainly relies on the energy-intensive Haber–Bosch process with the release of a large amount of CO2. Electrochemical fixation of N2 to NH3 under ambient conditions is an environmentally friendly and sustainable alternative, but the N2 reduction reaction (NRR) requires stable and efficient electrocatalysts. In this work, we report that the electrocatalytic NRR activity of Pd nanoparticles can be improved by surface modification with oxygen-rich tannic acid. The electrochemical test results in 0.1 M Na2SO4 suggest that such a catalyst achieves a large NH3 yield of 24.12 μg h−1 mgcat.−1 and a high faradaic efficiency of 9.49% at −0.45 V vs. the reversible hydrogen electrode (RHE), rivaling the performances of most of the reported aqueous-based NRR electrocatalysts. In addition, it also shows strong long-term electrochemical stability. [ABSTRACT FROM AUTHOR]

The interaction of chemokine (C-X-C motif) ligand 10 (CXCL10) with its receptor (CXCR3) is a critical process in recruiting donor reactive T cells to a graft and alloantigen-specific memory T (Tm) cells exert a principal function in promoting graft dysfunction during accelerated cardiac rejection. However, whether CXCL10 chemokine exerts any effects on acute accelerated rejection mediated by CD8+ Tm cells in a re-transplant model has remained elusive. The present study established a cardiac transplant model by advanced microsurgery technology and improved organ storage. A novel rat model of cardiac re-transplantation was established at 40 days following primary heart transplant. The experiment included two parts, and when models were established, the rats were divided into two groups: Primary cardiac transplant (HTx) and re-transplantation without treatment (HRTx). In part 1, recipients from part 2, including re-transplantation without treatment (HRTx+NS) and re-transplantation treated with anti-CXCL10 antibodies (500 µg every other day by intraperitoneal injection; HRTx+CXCL10 Abs group). The graft survival time was observed and graft infiltration by inflammatory cells was assessed via histology of cardiac graft sections; in addition, the gene expression and the serum concentration of CXCL10 in each group was assessed. Indexes such as rejection-associated cytokines were assayed by reverse-transcription quantitative PCR and ELISA kits, and flow cytometry of splenocytes was used to detect Tm cells in the re-transplantation groups. The results demonstrated that level of CXCL10 was significantly increased and the graft mean survival time was shortened accompanied with aggravated lymphocyte cell infiltration in the HRTx group when compared that in the HTx group; in addition, the serum levels and mRNA expression of interleukin (IL)-2 and interferon (IFN)-γ were increased, while transforming growth factor (TGF)-β was decreased in the HRTx group. Furthermore, neutralization of CXCL10 prolonged the graft mean survival time and delayed accelerated rejection. Compared with that in the HRTx+NS group, serum levels and graft tissue mRNA expression of IFN-γ and IL-2 were decreased in the HRTx+CXCL10 Abs group, while TGF-β mRNA was significantly increased but the serum concentration was not significantly affected. In addition, there was no difference in IL-10 between the two groups, while delayed accelerated rejection paralleled with inflammatory cell infiltration decreased and the proliferation and differentiation of CD8+ Tm cells in secondary lymphoid organs were reduced in the HRTx+CXCL10 Abs group vs. those in the HRTx+NS group. The present study demonstrated that CXCL10 had a crucial role in cardiac transplantation and re-transplantation, and that treatment with CXCL10 antibodies delays accelerated acute rejection mediated by Tm cells in a rat model of cardiac re-transplantation. [ABSTRACT FROM AUTHOR]

Net primary productivity (NPP) is the total amount of organic matter fixed by plants from the atmosphere through photosynthesis and is susceptible to the influences of climate change and human activities. In this study, we employed actual NPP (ANPP), potential NPP (PNPP), and human activity-induced NPP (HNPP) based on the Hurst exponent and statistical analysis to analyze the characteristics of vegetation productivity dynamics and to evaluate the effects of climate and human factors on vegetation productivity in Northeast China (NEC). The increasing trends in ANPP, PNPP, and HNPP accounted for 81.62%, 94.90%, and 89.63% of the total area, respectively, and ANPP in 68.64% of the total area will continue to increase in the future. Climate change played a leading role in vegetation productivity dynamics, which promoted an increase in ANPP in 71.55% of the area, and precipitation was the key climate factor affecting ANPP. The aggravation of human activities, such as increased livestock numbers and intensified agricultural activities, resulted in a decrease in ANPP in the western grasslands, northern Greater Khingan Mountains, and eastern Songnen Plain. In particular, human activities led to a decrease in ANPP in 53.84% of deciduous needleleaf forests. The impact of climate change and human activities varied significantly under different topography, and the percentage of the ANPP increase due to climate change decreased from 71.13% to 53.9% from plains to urgent slopes; however, the percentage of ANPP increase due to human activities increased from 3.44% to 21.74%, and the effect of human activities on the increase of ANPP was more obvious with increasing slope. At different altitudes, the difference in the effect of these two factors was not significant. The results are significant for understanding the factors influencing the vegetation productivity dynamics in NEC and can provide a reference for governments to implement projects to improve the ecosystem. [ABSTRACT FROM AUTHOR]

Recent studies reported that advanced glycation end products (AGEs) and endothelial-to-mesenchymal transition (EndMT) were involved in the calcific aortic valve disease (CAVD). However, the roles of AGEs in EndMT in the development of CAVD have not been elucidated. In this study, six-week-old male Apoe −/− mice were divided into four groups based on the following feeding periods: 0, 2, 4, and 6 months. The latter three groups were further divided into three subgroups corresponding to the following diet treatments: normal diet, high-fat diet + normal saline injection, and high-fat diet + aminoguanidine injection. Weight gain was monitored weekly. Finally, heart echocardiographic assessments were performed, and serum lipid levels, the protein expression and the histological changes in the aortic valves were determined. Results showed that the AGE inhibitor aminoguanidine alleviated the transaortic valve velocity and decreased the total cholesterol and low-density lipoprotein cholesterol levels. Calcification and carboxymethyl-lysine deposition were firstly detected around the aortic valve surfaces, whereas aminoguanidine injection attenuated their accumulation. In the early stage, HFD-activated AGEs-RAGE signaling resulted in the alpha-smooth muscle actin (α-SMA) upregulation and the vascular endothelium cadherin (VE-cadherin) downregulation on the valve endothelial layer. The activation resulted in early the transforming growth factor-β1 (TGF-β1) and the alkaline phosphatase (ALP) upregulation, and simultaneously reduced the bone morphogenetic protein receptor type II (BMPR2) expression. However, aminoguanidine restricted these proteins changes by inhibiting the interaction of AGEs and RAGE. In addition, immunofluorescence images showed obvious double-positive staining of ALP and α-SMA on the valve surfaces, revealing the contribution of EndMT to the early calcification. Therefore, this study demonstrates that activation of the AGEs-RAGE axis induced EndMT, promoting the progression of the aortic valve calcification in the initial stage via the counteraction of BMPR2 and TGF-β1 signaling. • AGEs is a novel mediator connecting LDL and the aortic valve calcification. • Activated AGEs-RAGE axis contributes to the aortic valve calcification. • AGEs-RAGE axis induces EndMT in calcification via counteraction of BMPR2 and TGF-β1. • Inhibited RAGE alleviates BMPR2 downregulation and TGF-β1 upregulation at the early stage. [ABSTRACT FROM AUTHOR]

The increasing number of extreme climate events is having a great impact on the terrestrial ecosystem. In this study, we applied a Taylor diagram to evaluate the 7 extreme temperature indices (ETI) of 12 models and the multi-model ensemble (MME) mean from phase 5 of the Coupled Model Intercomparison Project (CMIP5) during 1961–2005, and found that the MME has the best simulation effect. Warm indices and warm duration indices increase slowly, rapidly, and extremely under the representative concentration pathway 2.6 (RCP2.6), RCP4.5, and RCP8.5 scenarios, respectively. In contrast, the decrease in cold indices and cold duration indices are slow, rapid and extreme, respectively. The ETI from 2021–2100 under the RCP2.6 and RCP4.5 scenarios have primary periods ranging from 1–16 years. Under the RCP2.6 and RCP4.5 scenarios, the changes of warm indices are relatively largest in the basin of the central, and southeastern, while, under the RCP8.5 scenario, the changes are relatively significant, except for basin of northeast. The cold indices have the most significant decreasing trend in the Tibetan Plateau and its surrounding areas, under the three RCP scenarios. The findings from this study can provide reference for the risk management and prevention of climate disasters in the context of climate change in mainland China. [ABSTRACT FROM AUTHOR]

Vegetation phenology and photosynthetic primary production have changed simultaneously over the past three decades, thus impacting the velocity of vegetation greenup (Vgreenup) and withering (Vwithering). Although climate warming reduces the frequency of frost events, vegetation is exposed more frequently to frost due to the extension of the growing season. Currently, little is known about the effect of frost during the growing season on Vgreenup and Vwithering. This study analyzed spatiotemporal variations in Vgreenup and Vwithering in Northeast China between 1982 to 2015 using Global Inventory Modeling and Mapping Studies Normalized Difference Vegetation Index (GIMMS 3g NDVI) data. Frost days and frost intensity were selected as indicators to investigate the influence of frost during the growing season on Vgreenup and Vwithering, respectively. Increased frost days during the growing season slowed Vgreenup and Vwithering. The number of frost days had a greater impact on Vwithering compared to Vgreenup. In addition, Vgreenup and Vwithering of forests were more vulnerable to frost days, while frost days had a lesser effect on grasslands. In contrast to frost days, frost intensity, which generally decreased during the growing season, accelerated Vgreenup and Vwithering for all land cover types. Changes in frost intensity had less of an impact on forests, whereas the leaf structure of grasslands is relatively simple and thus more vulnerable to frost intensity. The effects of frost during the growing season on Vgreenup and Vwithering in Northeast China were highlighted in this study, and the results provide a useful reference for understanding local vegetation responses to global climate change. [ABSTRACT FROM AUTHOR]

With climate change, significant fluctuations in wildfires have been observed on the Mongolian Plateau. The ability to predict the distribution of wildfires in the context of climate change plays a critical role in wildfire management and ecosystem maintenance. In this paper, Ripley's K function and a Random Forest (RF) model were applied to analyse the spatial patterns and main influencing factors affecting the occurrence of wildfire on the Mongolian Plateau. The results showed that the wildfires were mainly clustered in space due to the combination of influencing factors. The distance scale is less than 1/2 of the length of the Mongolian Plateau; that is, it does not experience boundary effects in the study area and it meets the requirements of Ripley's K function. Among the driving factors, the fraction of vegetation coverage (FVC), land use degree (La), elevation, precipitation (pre), wet day frequency (wet), and maximum temperature (tmx) had the greatest influences, while the aspect had the lowest influence. The likelihood of fire was mainly concentrated in the northern, eastern, and southern parts of the Mongolian Plateau and in the border area between the Inner Mongolia Autonomous Region (Inner Mongolia) and Mongolian People's Republic (Mongolia), and wildfires did not occur or occurred less frequently in the hinterland area. The fitting results of the RF model showed a prediction accuracy exceeding 90%, which indicates that the model has a high ability to predict wildfire occurrences on the Mongolian Plateau. This study can provide a reference for predictions and decision-making related to wildfires on the Mongolian Plateau. [ABSTRACT FROM AUTHOR]

Vegetation phenology is the most intuitive and sensitive biological indicator of environmental conditions, and the start of the season (SOS) can reflect the rapid response of terrestrial ecosystems to climate change. At present, the model based on mean temperature neglects the role of the daytime maximum temperature (TMAX) and the nighttime minimum temperature (TMIN) in providing temperature accumulation and cold conditions at leaf onset. This study analyzed the spatiotemporal variations of spring phenology for the boreal forest from 2001 to 2017 based on the moderate-resolution imaging spectro-radiometer (MODIS) enhanced vegetation index (EVI) data (MOD13A2) and investigated the asymmetric effects of daytime and nighttime warming on the boreal forest spring phenology during TMAX and TMIN preseason by partial correlation analysis. The results showed that the spring phenology was delayed with increasing latitude of the boreal forest. Approximately 91.37% of the region showed an advancing trend during the study period, with an average advancement rate of 3.38 ± 0.08 days/decade, and the change rates of different land cover types differed, especially in open shrubland. The length of the TMIN preseason was longer than that of the TMAX preseason and diurnal temperatures showed an asymmetrical increase during different preseasons. The daytime and nighttime warming effects on the boreal forest are asymmetrical. The TMAX has a greater impact on the vegetation spring phenology than TMIN as a whole and the effect also has seasonal differences; the TMAX mainly affects the SOS in spring, while TMIN has a greater impact in winter. The asymmetric effects of daytime and nighttime warming on the SOS in the boreal forest were highlighted in this study, and the results suggest that diurnal temperatures should be added to the forest terrestrial ecosystem model. [ABSTRACT FROM AUTHOR]

Wildfires are one of the important disturbance factors in natural ecosystems and occur frequently around the world. Detailed research on the impact of wildfires is crucial not only for the development of livestock husbandry but also for the sustainable use of natural resources. In this study, based on the Moderate Resolution Imaging Spectroradiometer (MODIS) burned area product MC464A1 and site snow depth measurements, the kernel density estimation method (KDE), unary linear regression analysis, Sen + Mann-Kendall trend analysis, correlation analysis, and R/S analysis were used to evaluate the relationship between snow and spring wildfires (SWFs) in Hulunbuir. Our results indicated that SWFs decreased during the period of 2001–2018, were mainly distributed in the eastern portion of the study area, and that the highest SWF density was 7 events/km2. In contrast, the maximum snow depth increased during the period of 2001–2018 and the snow depth was deeper in the middle but shallower in the east and west. The SWFs and snow depth have significant negative correlations over space and time. The snow depth mainly affects the occurrence of SWFs indirectly by affecting the land surface temperature (LST) and Land Surface Water Index (LSWI) in spring. The snow depth was positively correlated with the LSWI in most of Hulunbuir and strongly negatively correlated with the LST, and this correlation was stronger in the eastern and western regions of Hulunbuir. The results of the Hurst exponent indicated that in the future, the snow depth trend will be opposite that of the current state, meaning that the trend of decreasing snow depth will increase dramatically in most of the study area, and SWFs may become more prominent. According to the validation results, the Hurst exponent is a reliable method for predicting the snow depth tendency. This research can be based on the snow conditions of the previous year to identify areas where fires are most likely to occur, enabling an improved and more targeted preparation for spring fire prevention. Additionally, the present study expands the theory and methods of wildfire occurrence research and promotes research on disasters and disaster chains. [ABSTRACT FROM AUTHOR]

Background. There were controversies over the relationship between Anion gap (AG) and mortality in critically ill patients. Therefore, a large multicenter cohort study was conducted to evaluate the association of AG and mortality in large-scale intensive care units (ICUs) patients. Methods. This retrospective cohort study included adult ICU patients enrolled from eICU Collaborative Research Database. According to initial serum AG upon ICU admission, patients were divided into three groups: AG < 8 mmol / L , 8 ≤ AG ≤ 16 mmol / L , and AG > 16 mmol / L. Logistic regression models were built to investigate the association between serum AG and ICU and hospital mortalities. Serum AG was added into Acute Physiology and Chronic Health Evaluation (APACHE) IV score and the model discrimination was assessed by the area under the curve (AUC) of receiver operating characteristic curves. The relationship between serum AG and mortalities in patients with different acid-base status and serum lactate were also evaluated. An external validation was performed with the Critical care database comprising patients with infection at Zigong Fourth People's Hospital. Results. A total of 8520 patients entered the final cohort. There are 42 patients with serum AG < 8 mmol / L , 3238 patients with 8 ≤ AG ≤ 16 mmol / L , and 5240 patients with AG > 16 mmol / L. Serum AG > 16 mmol / L is related with increased ICU mortality (odds ratio [OR], 1.530; 95% confidence interval [CI], 1.305–1.794) and hospital mortality (OR, 1.618; 95% CI, 1.415–1.849), compared with 8 ≤ AG ≤ 16 mmol / L. Adding Serum AG to APACHE IV score could statistically improve the prediction of ICU (0.770 [0.761–0.779] to 0.774 [0.765–0.783], P = 0.001) and hospital mortalities (0.756 [0.747–0.765] to 0.761 [0.751–0.770], P = 0.012). The associations between serum AG and mortalities remain robust in patients with different acid-base statuses and serum lactate. The findings are validated in the external cohort. Conclusions. Initial serum AG > 16 mmol / L after ICU admission is associated with increased mortality in critically ill patients. [ABSTRACT FROM AUTHOR]

Background: Previous observational studies have investigated the association between educational attainment and sepsis, pneumonia, and urinary tract infections (UTIs). However, their findings have been susceptible to reverse causality and confounding factors. Furthermore, no study has examined the effect of educational level on the risk of infections of the skin and subcutaneous tissue (SSTIs). Thus, we aimed to evaluate the causal relationships between educational level and the risk of four infectious diseases using Mendelian randomisation (MR) techniques., Methods: We used univariable MR analysis to investigate the causal associations between educational attainment (years of schooling (n = 766 345) and holding college or university degree (n = 334 070)) and four infectious diseases (sepsis (n = 486 484), pneumonia (n = 486 484), UTIs (n = 463 010), and SSTIs (n = 218 792)). We included genetic instrumental variables with a genome-wide significance (P < 5 × 10 -8 ) in the study. We used inverse variance-weighted estimation in the primary analysis and explored the stability of the results using multivariable MR analysis after adjusting for smoking, alcohol consumption, and body mass index., Results: Genetically predicted years of schooling were associated with a reduced risk of sepsis (odds ratio (OR) = 0.763; 95% confidence interval (CI) = 0.668-0.870, P = 5.525 × 10 -5 ), pneumonia (OR = 0.637; 95% CI = 0.577-0.702, P = 1.875 × 10 -19 ), UTIs (OR = 0.995; 95% CI = 0.993-0.997, P = 1.229 × 10 -5 ), and SSTIs (OR = 0.696; 95% CI = 0.605-0.801, P = 4.034 × 10 -7 ). We observed consistent results for the correlation between qualifications and infectious diseases. These findings remained stable in the multivariable MR analyses., Conclusions: Our findings suggest that increased educational attainment may be causally associated with a decreased risk of sepsis, pneumonia, UTIs, and SSTIs., Competing Interests: Disclosure of interest: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and declare no conflicts of interest., (Copyright © 2024 by the Journal of Global Health. All rights reserved.)

Background: Several clinical trials have demonstrated that glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) reduce the incidence of non-fatal myocardial infarction (MI) in patients with type 2 diabetes mellitus (T2DM). However, the underlying mechanism remains unclear. In this study, we applied a network pharmacology method to investigate the mechanisms by which GLP-1RAs reduce MI occurrence in patients with T2DM. Methods: Targets of three GLP-1RAs (liraglutide, semaglutide, and albiglutide), T2DM, and MI were retrieved from online databases. The intersection process and associated targets retrieval were employed to obtain the related targets of GLP-1RAs against T2DM and MI. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genes (KEGG) enrichment analyses were performed. The STRING database was used to obtain the protein-protein interaction (PPI) network, and Cytoscape was used to identify core targets, transcription factors, and modules. Results: A total of 198 targets were retrieved for the three drugs and 511 targets for T2DM with MI. Finally, 51 related targets, including 31 intersection targets and 20 associated targets, were predicted to interfere with the progression of T2DM and MI on using GLP-1RAs. The STRING database was used to establish a PPI network comprising 46 nodes and 175 edges. The PPI network was analyzed using Cytoscape, and seven core targets were screened: AGT, TGFB1, STAT3, TIMP1, MMP9, MMP1, and MMP2. The transcription factor MAFB regulates all seven core targets. The cluster analysis generated three modules. The GO analysis for 51 targets indicated that the terms were mainly enriched in the extracellular matrix, angiotensin, platelets, and endopeptidase. The results of KEGG analysis revealed that the 51 targets primarily participated in the renin-angiotensin system, complement and coagulation cascades, hypertrophic cardiomyopathy, and AGE-RAGE signaling pathway in diabetic complications. Conclusion: GLP-1RAs exert multi-dimensional effects on reducing the occurrence of MI in T2DM patients by interfering with targets, biological processes, and cellular signaling pathways related to atheromatous plaque, myocardial remodeling, and thrombosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Deng, Ren, Li, Li, Jin, Li, Liu, Gao, Zhang, Wang and Wang.)

The interaction of chemokine (C-X-C motif) ligand 10 (CXCL10) with its receptor (CXCR3) is a critical process in recruiting donor reactive T cells to a graft and alloantigen-specific memory T (Tm) cells exert a principal function in promoting graft dysfunction during accelerated cardiac rejection. However, whether CXCL10 chemokine exerts any effects on acute accelerated rejection mediated by CD8 + Tm cells in a re-transplant model has remained elusive. The present study established a cardiac transplant model by advanced microsurgery technology and improved organ storage. A novel rat model of cardiac re-transplantation was established at 40 days following primary heart transplant. The experiment included two parts, and when models were established, the rats were divided into two groups: Primary cardiac transplant (HTx) and re-transplantation without treatment (HRTx). In part 1, recipients from part 2, including re-transplantation without treatment (HRTx+NS) and re-transplantation treated with anti-CXCL10 antibodies (500 µg every other day by intraperitoneal injection; HRTx+CXCL10 Abs group). The graft survival time was observed and graft infiltration by inflammatory cells was assessed via histology of cardiac graft sections; in addition, the gene expression and the serum concentration of CXCL10 in each group was assessed. Indexes such as rejection-associated cytokines were assayed by reverse-transcription quantitative PCR and ELISA kits, and flow cytometry of splenocytes was used to detect Tm cells in the re-transplantation groups. The results demonstrated that level of CXCL10 was significantly increased and the graft mean survival time was shortened accompanied with aggravated lymphocyte cell infiltration in the HRTx group when compared that in the HTx group; in addition, the serum levels and mRNA expression of interleukin (IL)-2 and interferon (IFN)-γ were increased, while transforming growth factor (TGF)-β was decreased in the HRTx group. Furthermore, neutralization of CXCL10 prolonged the graft mean survival time and delayed accelerated rejection. Compared with that in the HRTx+NS group, serum levels and graft tissue mRNA expression of IFN-γ and IL-2 were decreased in the HRTx+CXCL10 Abs group, while TGF-β mRNA was significantly increased but the serum concentration was not significantly affected. In addition, there was no difference in IL-10 between the two groups, while delayed accelerated rejection paralleled with inflammatory cell infiltration decreased and the proliferation and differentiation of CD8 + Tm cells in secondary lymphoid organs were reduced in the HRTx+CXCL10 Abs group vs. those in the HRTx+NS group. The present study demonstrated that CXCL10 had a crucial role in cardiac transplantation and re-transplantation, and that treatment with CXCL10 antibodies delays accelerated acute rejection mediated by Tm cells in a rat model of cardiac re-transplantation.