Distribution, risk evaluation, and source allocation of cesium and strontium in surface soil in a mining city.

Radioactive nuclides cesium (Cs) and strontium (Sr) possess long half-lives, with 135Cs at approximately 2.3 million years and 87Sr at about 49 billion years. Their persistent accumulation can result in long-lasting radioactive contamination of soil ecosystems. This study employed geo-accumulation index (Igeo), pollution load index (PLI), potential ecological risk index (PEPI), health risk assessment model (HRA), and Monte Carlo simulation to evaluate the pollution and health risks of Cs and Sr in the surface soil of different functional areas in a typical mining city in China. Positive matrix factorization (PMF) model was used to elucidate the potential sources of Cs and Sr and the respective contribution rates of natural and anthropogenic sources. The findings indicate that soils in the mining area exhibited significantly higher levels of Cs and Sr pollution compared to smelting factory area, agricultural area, and urban residential area. Strontium did not pose a potential ecological risk in any studied functional area. The non-carcinogenic health risk of Sr to the human body in the study area was relatively low. Because of the lack of parameters for Cs, the potential ecological and human health risks of Cs was not calculated. The primary source of Cs in the soil was identified as the parent material from which the soil developed, while Sr mainly originated from associated contamination caused by mining activities. This research provides data for the control of Cs and Sr pollution in the surface soil of mining city.

SIVA-1 interaction with PCBP1 serves as a predictive biomarker for cisplatin sensitivity in gastric cancer and its inhibitory effect on tumor growth in vivo.

Background: SIVA-1 has been reported to play a key role in cell apoptosis and gastric cancer (GC) chemoresistance in vitro. Nevertheless, the clinical significance of SIVA-1 in GC chemotherapy remains unclear. Methods and results: Immunohistochemistry and histoculture drug response assays were used to determine SIVA-1 expression and the inhibition rate (IR) of agents to GC and to further analyze the relationship between these two phenomena. Additionally, cisplatin (DDP)-resistant GC cells were used to elucidate the role and mechanism of SIVA-1 in vivo. The results demonstrated that SIVA-1 expression was positively correlated with the IR of DDP to GC but not with those of 5-fluorouracil (5-FU) or adriamycin (ADM). Furthermore, SIVA-1 overexpression with DDP treatment synergistically inhibited tumor growth in vivo by increasing PCBP1 and decreasing Bcl-2 and Bcl-xL expression. Conclusions: Our study demonstrated that SIVA-1 may serve as an indicator of the GC sensitivity to DDP, and the mechanism of SIVA-1 in GC resistance to DDP was preliminarily revealed.

Safety of Mechanical Thrombectomy for Acute Ischemic Stroke in Patients with Thrombocytopenia.

BACKGROUND AND AIM: The impact of low platelet count on outcomes in patients with Acute Ischemic Stroke (AIS) undergoing Mechanical Thrombectomy (MT) is still unclear. In this study we have further explored the effect of thrombocytopenia on the safety and efficacy of MT in patients with anterior circulation Large Vessel Occlusion (LVO) stroke. MATERIALS AND METHODS: Patients with AIS who underwent MT at our center between June 2015 and November 2021 were examined. Based on the platelet count recorded on admission patients were divided into two groups: those with thrombocytopenia (<150 × 109/L) and those without thrombocytopenia (≥ 150 × 109/L). Symptomatic Intracranial Hemorrhage (sICH) was the primary safety outcome. The efficacy outcome was functional independence defined as a 90-day modified Rankin Scale (mRS) score of 0-2. Multivariate logistic regression models were used to determine the risk factors for post-procedure sICH and 90-day functional outcomes. RESULTS: Among 302 patients included in the study, thrombocytopenia was detected in 111 (36.8%) cases. Univariate analysis showed age, the proportion of atrial fibrillation, the rates of sICH, 90-day poor outcomes, and mortality to be higher in patients with thrombocytopenia (all p < 0.05). Multivariable analysis showed thrombocytopenia to be independently associated with a higher rate of sICH (OR 2.022, 95% CI 1.074-3.807, p =0.029) however, thrombocytopenia did not affect the 90-day functional outcomes (OR 1.045, 95%CI 0.490-2.230, p =0.909) and mortality (OR 1.389, 95% CI 0.467- 4.130 p = 0.554). CONCLUSION: Thrombocytopenia may increase the risk of sICH but not affect the 90-day functional outcomes and mortality in patients with AIS treated with MT.

Predicting distant metastasis in nasopharyngeal carcinoma using gradient boosting tree model based on detailed magnetic resonance imaging reports.

BACKGROUND: Development of distant metastasis (DM) is a major concern during treatment of nasopharyngeal carcinoma (NPC). However, studies have demonstrated improved distant control and survival in patients with advanced NPC with the addition of chemotherapy to concomitant chemoradiotherapy. Therefore, precise prediction of metastasis in patients with NPC is crucial. AIM: To develop a predictive model for metastasis in NPC using detailed magnetic resonance imaging (MRI) reports. METHODS: This retrospective study included 792 patients with non-distant metastatic NPC. A total of 469 imaging variables were obtained from detailed MRI reports. Data were stratified and randomly split into training (50%) and testing sets. Gradient boosting tree (GBT) models were built and used to select variables for predicting DM. A full model comprising all variables and a reduced model with the top-five variables were built. Model performance was assessed by area under the curve (AUC). RESULTS: Among the 792 patients, 94 developed DM during follow-up. The number of metastatic cervical nodes (30.9%), tumor invasion in the posterior half of the nasal cavity (9.7%), two sides of the pharyngeal recess (6.2%), tubal torus (3.3%), and single side of the parapharyngeal space (2.7%) were the top-five contributors for predicting DM, based on their relative importance in GBT models. The testing AUC of the full model was 0.75 (95% confidence interval [CI]: 0.69-0.82). The testing AUC of the reduced model was 0.75 (95%CI: 0.68-0.82). For the whole dataset, the full (AUC = 0.76, 95%CI: 0.72-0.82) and reduced models (AUC = 0.76, 95%CI: 0.71-0.81) outperformed the tumor node-staging system (AUC = 0.67, 95%CI: 0.61-0.73). CONCLUSION: The GBT model outperformed the tumor node-staging system in predicting metastasis in NPC. The number of metastatic cervical nodes was identified as the principal contributing variable.

Aerobic exercise alleviates skeletal muscle aging in male rats by inhibiting apoptosis via regulation of the Trx system.

Skeletal muscle aging in rats is a reduction in skeletal muscle mass caused by a decrease in the number or volume of skeletal muscle myofibers. Apoptosis has been recognized to play a key role in accelerating the process of skeletal muscle aging in rats. The thioredoxin (Trx) system is a widely expressed oxidoreductase system that controls the cellular reduction/oxidation state and has both potent anti-free radical damage and important pro-growth and apoptosis inhibitory functions. Previous studies have shown that exercise delays skeletal muscle aging. However, it is unclear whether exercise attenuates skeletal muscle aging via the Trx system. Therefore, the present study used the Trx system as an entry point to explore the effect of aerobic exercise to improve skeletal muscle aging in rats and its possible mechanisms, and to provide a theoretical basis for exercise to delay skeletal muscle aging in rats. It was shown that aerobic exercise in senescent rats resulted in increased gastrocnemius index, decreased body weight, increased endurance, decreased skeletal muscle cell apoptosis, increased activity and protein expression of the Trx system, and decreased expression of p38 and ASK1. Based on these findings, we conclude that 10 weeks of aerobic exercise may enhance the anti-apoptotic effect of Trx by up-regulating Trx and Trx reductase (TR) protein expression, which in turn increases Trx activity in rat skeletal muscle, and ultimately alleviates apoptosis in senescent skeletal muscle cells.

Regulation of a single inositol 1-phosphate synthase homeologue by HSFA6B contributes to fibre yield maintenance under drought conditions in upland cotton.

Drought stress substantially impacts crop physiology resulting in alteration of growth and productivity. Understanding the genetic and molecular crosstalk between stress responses and agronomically important traits such as fibre yield is particularly complicated in the allopolyploid species, upland cotton (Gossypium hirsutum), due to reduced sequence variability between A and D subgenomes. To better understand how drought stress impacts yield, the transcriptomes of 22 genetically and phenotypically diverse upland cotton accessions grown under well-watered and water-limited conditions in the Arizona low desert were sequenced. Gene co-expression analyses were performed, uncovering a group of stress response genes, in particular transcription factors GhDREB2A-A and GhHSFA6B-D, associated with improved yield under water-limited conditions in an ABA-independent manner. DNA affinity purification sequencing (DAP-seq), as well as public cistrome data from Arabidopsis, were used to identify targets of these two TFs. Among these targets were two lint yield-associated genes previously identified through genome-wide association studies (GWAS)-based approaches, GhABP-D and GhIPS1-A. Biochemical and phylogenetic approaches were used to determine that GhIPS1-A is positively regulated by GhHSFA6B-D, and that this regulatory mechanism is specific to Gossypium spp. containing the A (old world) genome. Finally, an SNP was identified within the GhHSFA6B-D binding site in GhIPS1-A that is positively associated with yield under water-limiting conditions. These data lay out a regulatory connection between abiotic stress and fibre yield in cotton that appears conserved in other systems such as Arabidopsis.

What is said about #donateliver or #liverdonor? Reflexive thematic analysis of Twitter (X) posts from 2012 to 2022.

BACKGROUND: There is sustained interest in understanding the perspectives of liver transplant recipients and living donors, with several qualitative studies shedding light on this emotionally charged subject. However, these studies have relied primarily on traditional semi-structured interviews, which, while valuable, come with inherent limitations. Consequently, there remains a gap in our comprehension of the broader public discourse surrounding living liver donation. This study aims to bridge this gap by delving into public conversations related to living liver donation through a qualitative analysis of Twitter (now X) posts, offering a fresh perspective on this critical issue. METHODS: To compile a comprehensive dataset, we extracted original tweets containing the hashtags "#donateliver" OR "#liverdonor", all posted in English from January 1, 2012, to December 31, 2022. We then selected tweets from individual users whose Twitter (X) accounts featured authentic human names, ensuring the credibility of our data. Employing Braun and Clarke's reflexive thematic analysis approach, the study investigators read and analysed the included tweets, identifying two main themes and six subthemes. The Health Policy Triangle framework was applied to understand the roles of different stakeholders involved in the discourse and suggest areas for policy improvement. RESULTS: A total of 361 unique tweets from individual users were analysed. The major theme that emerged was the persistent shortage of liver donors, underscoring the desperation faced by individuals in need of life-saving liver transplants and the urgency of addressing the organ shortage problem. The second theme delved into the experiences of liver donors post-surgery, shedding light on a variety of aspects related to the transplantation process, including the visibility of surgical scars, and the significance of returning to physical activity and exercise post-surgery. CONCLUSION: The multifaceted experiences of individuals involved in the transplantation process, both recipients and donors, should be further studied in our efforts to improve the critical shortage of liver donors.

CTSD upregulation as a key driver of spinal ligament abnormalities in spinal stenosis.

Spinal stenosis (SS) is frequently caused by spinal ligament abnormalities, such as ossification and hypertrophy, which narrow the spinal canal and compress the spinal cord or nerve roots, leading to myelopathy or sciatic symptoms; however, the underlying pathological mechanism is poorly understood, hampering the development of effective nonsurgical treatments. Our study aims to investigate the role of co-expression hub genes in patients with spinal ligament ossification and hypertrophy. To achieve this, we conducted an integrated analysis by combining RNA-seq data of ossification of the posterior longitudinal ligament (OPLL) and microarray profiles of hypertrophy of the ligamentum flavum (HLF), consistently pinpointing CTSD as an upregulated hub gene in both OPLL and HLF. Subsequent RT-qPCR and IHC assessments confirmed the heightened expression of CTSD in human OPLL, ossification of the ligamentum flavum (OLF), and HLF samples. We observed an increase in CTSD expression in human PLL and LF primary cells during osteogenic differentiation, as indicated by western blotting (WB). To assess CTSD's impact on osteogenic differentiation, we manipulated its expression levels in human PLL and LF primary cells using siRNAs and lentivirus, as demonstrated by WB, ALP staining, and ARS. Our findings showed that suppressing CTSD hindered the osteogenic differentiation potential of PLL and LF cells, while overexpressing CTSD activated osteogenic differentiation. These findings identify CTSD as a potential therapeutic target for treating spinal stenosis associated with spinal ligament abnormalities.

[Spatiotemporal Response of Ecosystem Service Value to Land Use Change in the Lanzhou-Xining Urban Agglomeration over the Past 20 Years].

With rapid urbanization and human activities exacerbating threats to the degradation of various ecosystem services in modern urban agglomerations, the exploration of the state of ecological security at the scale of urban agglomerations is of great significance. This study considered the Lanzhou-Xining Urban Agglomeration as the research area, based on the land use data in 2000, 2005, 2010, 2015, and 2020. At the same time, the landscape ecological risk index was introduced. The land use change characteristics of the Lanzhou-Xining Urban Agglomeration were analyzed by using the land use transfer matrix, the value per unit area equivalent factor method, and the bivariate spatial autocorrelation analysis method to elucidate the impacts of the changes in the ecological risk index induced by the land use transition on the value of ecosystem services. This study analyzed the land use change characteristics of the Lanzhou-Xining Urban Agglomeration and elucidated the impacts of changes in the ecological risk index on the value of ecosystem services caused by land use transformation. The results showed that:① During the period from 2000 to 2020, the land use types of the Lanzhou-Xining Urban Agglomeration were mainly dominated by grassland, cropland, and forest land. The construction land area had expanded significantly mainly from cropland and grassland, and the six land use types had strong cross-transformation. The total area of land use change was 6 646.05 km2. ② In terms of spatial changes, the spatial pattern of ecosystem service value in the Lanzhou-Xining Urban Agglomeration had not undergone obvious transformation. However, the regional variability was significant, generally showing the distribution characteristics of high in the northwest and low in the southeast. ③From the perspective of temporal change, the value of ecosystem services in the Lanzhou-Xining Urban Agglomeration showed an upward trend, with the total flow of value increasing from 186.459 billion yuan to 192.156 billion yuan, with a total value-added of 5.697 billion yuan. ④ There was a rising trend in the overall ecological risk index of the Lanzhou-Xining Urban Agglomeration over the past 20 years. Low ecological risk areas and lower ecological risk areas dominated the ecological risk areas. There was a significant positive correlation between the value of ecosystem services and the ecological risk index. This study aimed to reveal the understanding of the impacts of land-use practices on ecosystem service values and ecological risks, to provide important references for regional ecological risk management and land-use policy formulation, and thus to promote the high-quality development of the ecological environment in the Yellow River Basin.

Study on Spline Stress of Separator Plates in a Wet Multi-Plate Clutch.

The spline teeth fracture of separator plates in wet multi-plate clutches compromises driving safety and the vehicle's lifespan. Tooth fracture is mainly caused by stress concentration at the tooth root and uneven circumferential load distribution. This paper considers parameters such as torque, teeth count, tooth profile, and misalignment errors, establishing the corresponding finite element (FE) model to analyze the impact of the above-mentioned parameters on the strength of the separator plates. Analysis under even and biased load circumstances demonstrated that an optimum tooth count and profile can significantly increase the strength of the separator plates, offering advice for the optimized design of wet multi-plate clutch separator plates.

Intense Turbulent Bursts Promote the Release of Perfluoroalkyl Acids from Sediments at High Flow Velocity.

Despite frequent detection of high levels of perfluoroalkyl acids (PFAAs) in sediments, research on the environmental fate of PFAAs in sediments, particularly under hydrodynamic conditions, is rather limited, challenging effective management of PFAA loadings. Therefore, this study investigated the release and transport of 15 PFAAs in sediments under environmentally relevant flow velocities using recirculating flumes and revealed the underlying release mechanisms by identifying related momentum transfer. An increased velocity enhanced the release magnitude of total PFAAs by a factor of 3.09. The release capacity of short-chain PFAAs was notably higher than that of long-chain PFAAs, and this pattern was further amplified by flow velocity. Pore-water drainage was the major pathway for PFAA release, with the release amount predominantly determined by flow velocity-induced release intensity and depth, as well as affected by the perfluorocarbon chain length and sediment size. The weak anion exchanger-diffusion gradients in the thin-film technique confirmed that the release depth of PFAAs increased with flow velocity. Quadrant analysis revealed that the rise in the frequency and intensity of turbulent bursts driven by sweeps and ejections at high flow velocity was the underlying cause of the increased release magnitude and depth of PFAAs.

Gastrodin Ameliorates Post-Stroke Depressive-Like Behaviors Through Cannabinoid-1 Receptor-Dependent PKA/RhoA Signaling Pathway.

Post-stroke depression (PSD) is a significant complication in stroke patients, increases long-term mortality, and exaggerates ischemia-induced brain injury. However, the underlying molecular mechanisms and effective therapeutic targets related to PSD have remained elusive. Here, we employed an animal behavioral model of PSD by combining the use of middle cerebral artery occlusion (MCAO) followed by spatial restraint stress to study the molecular underpinnings and potential therapies of PSD. Interestingly, we found that sub-chronic application of gastrodin (Gas), a traditional Chinese medicinal herb Gastrodia elata extraction, relieved depression-related behavioral deficits, increased the impaired expression of synaptic transmission-associated proteins, and restored the altered spine density in hippocampal CA1 of PSD animals. Furthermore, our results indicated that the anti-PSD effect of Gas was dependent on membrane cannabinoid-1 receptor (CB1R) expression. The contents of phosphorated protein kinase A (p-PKA) and phosphorated Ras homolog gene family member A (p(ser188)-RhoA) were decreased in the hippocampus of PSD-mice, which was reversed by Gas treatment, and CB1R depletion caused a diminished efficacy of Gas on p-PKA and p-RhoA expression. In addition, the anti-PSD effect of Gas was partially blocked by PKA inhibition or RhoA activation, indicating that the anti-PSD effect of Gas is associated with the CB1R-mediated PKA/RhoA signaling pathway. Together, our findings revealed that Gas treatment possesses protective effects against the post-stroke depressive-like state; the CB1R-involved PKA/RhoA signaling pathway is critical in mediating Gas's anti-PSD potency, suggesting that Gas application may be beneficial in the prevention and adjunctive treatment of PSD.

Estimation of soybean yield based on high-throughput phenotyping and machine learning.

Introduction: Soybeans are an important crop used for food, oil, and feed. However, China's soybean self-sufficiency is highly inadequate, with an annual import volume exceeding 80%. RGB cameras serve as powerful tools for estimating crop yield, and machine learning is a practical method based on various features, providing improved yield predictions. However, selecting different input parameters and models, specifically optimal features and model effects, significantly influences soybean yield prediction. Methods: This study used an RGB camera to capture soybean canopy images from both the side and top perspectives during the R6 stage (pod filling stage) for 240 soybean varieties (a natural population formed by four provinces in China: Sichuan, Yunnan, Chongqing, and Guizhou). From these images, the morphological, color, and textural features of the soybeans were extracted. Subsequently, feature selection was performed on the image parameters using a Pearson correlation coefficient threshold ≥0.5. Five machine learning methods, namely, CatBoost, LightGBM, RF, GBDT, and MLP, were employed to establish soybean yield estimation models based on the individual and combined image parameters from the two perspectives extracted from RGB images. Results: (1) GBDT is the optimal model for predicting soybean yield, with a test set R2 value of 0.82, an RMSE of 1.99 g/plant, and an MAE of 3.12%. (2) The fusion of multiangle and multitype indicators is conducive to improving soybean yield prediction accuracy. Conclusion: Therefore, this combination of parameters extracted from RGB images via machine learning has great potential for estimating soybean yield, providing a theoretical basis and technical support for accelerating the soybean breeding process.

Release of perfluoroalkyl acids from sediments under the effects of the discharge ratio and flow flux at a Y-shaped confluence.

The sediments in riverine environments contain notably high concentrations of perfluoroalkyl acids (PFAAs), which may be released into the water body under different hydrodynamic forces, such as those occurring at Y-shaped confluences. The release of PFAAs may pose a significant risk to the surrounding aquatic ecosystems. However, our understanding of the release and transport of PFAAs from sediments at Y-shaped confluences remains unclear. Thus, in this study, we performed a series of flume experiments to explore the effects of discharge ratio and total flow flux on the release and redistribution of PFAAs. The results indicated that these two parameters significantly affected the hydrodynamic features of confluences and the water physicochemical parameters. PFAA concentrations in the dissolved phase and suspended particulate matter (SPM) rose significantly as the discharge ratio and total flow flux increased. The dissolved phase was the predominant loading form of PFAAs, with short-chain PFAAs being the main kind, while long-chain PFAAs were dominant in the SPM. The spatial distribution pattern of PFAAs in sediments at the confluence exhibited a high degree of correspondence with hydrodynamic zones. The separation zone and maximum velocity zone were consistent with sediment regions with low and high capacities to release PFAAs, respectively. The patterns of variation in PFAA distribution were comparable to those observed in hydrodynamic zones as the discharge ratio and total flow flux varied. Furthermore, these two parameters altered the partitioning behaviors of PFAAs; specifically, the PFAAs in sediments tended to be released into the pore-water, while the liberated PFAAs tended to attach to SPM. Linear regression and correlation analyses suggested that the stream-wise and vertical flow velocity components near the sediment-water interface were the primary contributors to sediment suspension and PFAA exchange between the water column and pore-water. These findings will help us to understand the patterns of PFAA release in sediments at Y-shaped confluences and assist in the management of PFAA-contaminated sediments at these locations.

A robust aluminum-octacarboxylate framework with scu topology for selective capture of sulfur dioxide.

The high structural diversity and porosity of metal-organic frameworks (MOFs) promote their applications in selective gas adsorption. The development of robust MOFs that are stable against corrosive SO2 remains a daunting challenge. Here, we report a highly robust aluminum-based MOF (HIAM-330) built on a 4-connected Al3(OH)2(COO)4 cluster and 8-connected octacarboxylate ligand with a (4,8)-connected scu topology. It exhibits a fully reversible SO2 uptake of 12.1 mmol g-1 at 298 K and 1 bar. It is capable of selective capture of SO2 over other gases (CO2, CH4, and N2) with high adsorption selectivities of 60, 330, and 3537 for equimolar mixtures of SO2/CO2, SO2/CH4, and SO2/N2, respectively, at 298 K and 1 bar. Breakthrough measurements verified the capability of HIAM-330 for selective capture of SO2 (2500 ppm) over CO2 or N2. High-resolution synchrotron X-ray powder diffraction of SO2 loaded HIAM-330 revealed the binding domains of adsorbed SO2 molecules and host-guest interactions.

[Changes and influence factors of soil matrix infiltration in Chinese fir plantations with different stand ages in northern Guangxi]. / æ¡‚åŒ—åœ°åŒºä¸åŒæž—é¾„æ‰æœ¨äººå·¥æž—åœŸå£¤åŸºè´¨å ¥æ¸—å˜åŒ–åŠå½±å“å› ç´ .

Soil matrix infiltration is an important pathway for plantations to obtain water, which affects ecological benefits and water conservation function of plantations. The changes of soil matrix infiltration and its influencing factors in different growth stages of Chinese fir plantations remain unclear. We measured soil matrix infiltration process using a tension infiltrometer in Chinese fir plantations (5, 8, 11, and 15 years old) of Beijiang River Forest Farm in Rongshui, Guangxi, and analyzed soil basic physicochemical properties to identify the dominant factors influencing soil matrix infiltration. The results showed that initial infiltration rate, stable infiltration rate, and cumulative infiltration increased with stand ages. The ranges of different stand ages were 141-180 mm·h-1, 109-150 mm·h-1, and 188-251 mm, respectively. The initial infiltration rate, stable infiltration rate, and cumulative infiltration were significantly positively correlated with soil capillary porosity, soil organic matter, soil water stable macroaggregate, sand content, and clay content, while negatively correlated with soil bulk density and silt content. Early thinning had a positive effect on soil matrix infiltration, but thinning measures after 11 years did not enhance soil matrix infiltration further. Philip model was optimal for describing soil matrix infiltration process in this region. In conclusion, soil matrix infiltration capacity of Chinese fir plantations gradually increased from young to middle-aged stands, but matrix infiltration capacity tended to stabilize after 11 years old. Silt content and water stable macroaggregate were the dominant factors influencing matrix infiltration.

Inflammatory proteins may mediate the causal relationship between gut microbiota and inflammatory bowel disease: A mediation and multivariable Mendelian randomization study.

This research investigates the causal relationships among gut microbiota, inflammatory proteins, and inflammatory bowel disease (IBD), including crohn disease (CD) and ulcerative colitis (UC), and identifies the role of inflammatory proteins as potential mediators. Our study analyzed gut microbiome data from 13,266 samples collected by the MiBioGen alliance, along with inflammatory protein data from recent research by Zhao et al, and genetic data on CD and UC from the International Inflammatory Bowel Disease Genetics Consortium (IIBDGC). We used Mendelian randomization (MR) to explore the associations, complemented by replication, meta-analysis, and multivariable MR techniques for enhanced accuracy and robustness. Our analysis employed several statistical methods, including inverse-variance weighting, MR-Egger, and the weighted median method, ensuring comprehensive and precise evaluation. After MR analysis, replication and meta-analysis, we revealed significant associations between 11 types of gut microbiota and 17 inflammatory proteins were associated with CD and UC. Mediator MR analysis and multivariable MR analysis showed that in CD, the CD40L receptor mediated the causal effect of Defluviitaleaceae UCG-011 on CD (mediation ratio 8.3%), and the Hepatocyte growth factor mediated the causal effect of Odoribacter on CD (mediation ratio 18%). In UC, the C-C motif chemokine 4 mediated the causal effect of Ruminococcus2 on UC (mediation ratio 4%). This research demonstrates the interactions between specific gut microbiota, inflammatory proteins, and CD and UC. Furthermore, the CD40L receptor may mediate the relationship between Defluviitaleaceae UCG-011 and CD; the Hepatocyte growth factor may mediate the relationship between Odoribacter and CD; and the C-C motif chemokine 4 may mediate the relationship between Ruminococcus2 and UC. The identified associations and mediation effects offer insights into potential therapeutic approaches targeting the gut microbiome for managing CD and UC.

Immunomodulation of adipose-derived mesenchymal stem cells on peripheral blood mononuclear cells in colorectal cancer patients with COVID-19.

BACKGROUND: Accumulating evidence has shown that adipose tissue-derived mesenchymal stem cells (ADSCs) are an effective therapeutic approach for managing coronavirus disease 2019 (COVID-19); however, further elucidation is required to determine their underlying immunomodulatory effect on the mRNA expression of T helper cell-related transcription factors (TFs) and cytokine release in peripheral blood mononuclear cells (PBMCs). AIM: To investigate the impact of ADSCs on the mRNA expression of TFs and cytokine release in PBMCs from colorectal cancer (CRC) patients with severe COVID-19 (CRC+ patients). METHODS: PBMCs from CRC+ patients (PBMCs-C+) and age-matched CRC patients (PBMCs-C) were stimulated and cultured in the presence/absence of ADSCs. The mRNA levels of T-box TF TBX21 (T-bet), GATA binding protein 3 (GATA-3), RAR-related orphan receptor C (RORC), and forkhead box P3 (FoxP3) in the PBMCs were determined by reverse transcriptase-polymerase chain reaction. Culture supernatants were evaluated for levels of interferon gamma (IFN-γ), interleukin 4 (IL-4), IL-17A, and transforming growth factor beta 1 (TGF-ß1) using an enzyme-linked immunosorbent assay. RESULTS: Compared with PBMCs-C, PBMCs-C+ exhibited higher mRNA levels of T-bet and RORC, and increased levels of IFN-γ and IL-17A. Additionally, a significant decrease in FoxP3 mRNA and TGF-ß1, as well as an increase in T-bet/GATA-3, RORC/FoxP3, IFN-γ/IL-4, and IL-17A/TGF-ß1 ratios were observed in PBMCs-C+. Furthermore, ADSCs significantly induced a functional regulatory T cell (Treg) subset, as evidenced by an increase in FoxP3 mRNA and TGF-ß1 release levels. This was accompanied by a significant decrease in the mRNA levels of T-bet and RORC, release of IFN-γ and IL-17A, and T-bet/GATA-3, RORC/FoxP3, IFN-γ/IL-4, and IL-17A/TGF-ß1 ratios, compared with the PBMCs-C+alone. CONCLUSION: The present in vitro studies showed that ADSCs contributed to the immunosuppressive effects on PBMCs-C+, favoring Treg responses. Thus, ADSC-based cell therapy could be a beneficial approach for patients with severe COVID-19 who fail to respond to conventional therapies.