LncRNA CRNDE promotes hepatoma cell proliferation by regulating the metabolic reprogramming of M2 macrophages via ERK pathway.

BACKGROUND: LncRNA colorectal neoplasia differentially expressed (CRNDE) was found to be an important regulator in many cancers. This project focuses on the function of CRNDE on macrophage metabolic reprogramming and Hepatocellular carcinoma (HCC). METHOD: qRT-PCR and Immunofluorescence were used to analyze Arg-1, IL-10, CD163, CCL-18, CD206, and CRNDE expression in HCC tissues and macrophages. Western Blotting was used to analyze ERK and p-ERK expression. Edu assay, transwell assay and xenograft experiments were carried out to study cell viability, migrated and invasive capability. Immunohistochemical staining was used to evaluate Ki67 expression. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) was performed for macrophages metabolites analysis. RESULTS: Arg-1, IL-10, CD163, CD206, and CRNDE were significantly up-regulated in HCC tissues, M2 macrophage and M0 macrophage with CRNDE overexpressed (OV-CRNDE-M0), which downregulated in M0 macrophage with CRNDE knockdown (sh-CRNDE-M0). The conditioned medium (CM) of M2 cells and OV-CRNDE-M0 cells promoted cell viability, invasion, and migration of HCC cells, the effect was reversed by sh-CRNDE-M0 cells CM. OV-CRNDE-M0 cells promoted tumor growth, Ki67 and CD206 expression in xenograft model. 61 metabolites were detected, of which 18 metabolites changed significantly in OV-CRNDE-M0 group compared to M0 group, with 9 upregulated and 9 downregulated. KEGG analysis showed the enrichment pathways were biosynthesis, glyoxylate and dicarboxylate metabolism. SMPDB analysis showed the enrichment pathways were hypoacetylaspartia, canavan disease, and aspartate metabolism. CONCLUSION: CRNDE regulated the metabolic reprogramming of M2 macrophage via ERK pathway, which thereby contributed to HCC proliferation, migration, and invasion.

METTL3 deficiency leads to ovarian insufficiency due to IL-1ß overexpression in theca cells.

Premature ovarian insufficiency (POI) is a clinical syndrome characterised by a decline in ovarian function in women before 40 years of age and is associated with oestradiol deficiency and a complex pathogenesis. However, the aetiology of POI is still unclear and effective preventative and treatment strategies are still lacking. Methyltransferase like 3 (METTL3) is an RNA methyltransferase that is involved in spermatogenesis, oocyte development and maturation, early embryonic development, and embryonic stem cell differentiation and formation, but its role in POI is unknown. In the present study, METTL3 deficiency in follicular theca cells was found to lead to reduced fertility in female mice, with a POI-like phenotype, and METTL3 knockout promoted ovarian inflammation. Further, a reduction in METTL3 in follicular theca cells led to a decrease in the m6A modification of pri-miR-21, which further reduced pri-miR-21 recognition and binding by DGCR8 proteins, leading to a decrease in the synthesis of mature miR-21-5p. Decrease of miR-21-5p promoted the secretion of interleukin-1ß (IL-1ß) from follicular theca cells. Acting in a paracrine manner, IL-1ß inhibited the cAMP-PKA pathway and activated the NF-κB pathway in follicular granulosa cells. This activation increased the levels of reactive oxygen species in granulosa cells, causing disturbances in the intracellular Ca2+ balance and mitochondrial damage. These cellular events ultimately led to granulosa cell apoptosis and a decrease in oestradiol synthesis, resulting in POI development. Collectively, these findings reveal how METTL3 deficiency promotes the expression and secretion of IL-1ß in theca cells, which regulates ovarian functions, and proposes a new theory for the development of POI disease.

A national study exploring the association between triglyceride-glucose index and risk of hyperuricemia events in adults with hypertension.

Background: The triglyceride-glucose (TyG) index has been recommended as a practical surrogate of insulin resistance (IR). However, the association between the TyG index and hyperuricemia among adults with hypertension remains to be elucidated. Methods: We included and analyzed 3134 HTN patients and 4233 non-HTN participants from the cross-sectional 2013-2018 U.S. National Health and Nutrition Examination Surveys (NHANES). Multivariable logistic regression and restricted cubic splines (RCS) were used to explore the association between the TyG index and hyperuricemia. Stratifed analyses were performed to assess the association in populations with different subgroups of hypertension. Results: The prevalence of hyperuricemia was higher in HTN patients (28.00 %) than in non-HTN participants (12.47 %). The multivariable logistic regression showed that the TyG index was significantly associated with hyperuricemia. After multivariable adjustment, higher TyG index levels were found to be associated with a higher prevalence of hyperuricemia in HTN patients (OR: 2.39, 95 % CI: 1.37-4.17, Ptrend < 0.001) and non-HTN participants (OR: 2.61, 95 % CI: 1.45-4.69, Ptrend < 0.001). Restricted cubic spline regression showed linearity of the associations between the TyG index and hyperuricemia (p-nonlinear > 0.05). In the subgroup analysis suggested that the positive association seemed to be strong among male, alcohol use, and diabetes group (P for interaction < 0.05). Conclusions: TyG index, a practical surrogate of IR, was linearly and positively associated with hyperuricemia in HTN and non-HTN participants. Proactive measures are needed to prevent the comorbidity of IR-driven hyperuricemia in the future.

Identification of an HLA-A*11:01-restricted neoepitope of mutant PIK3CA and its specific T cell receptors for cancer immunotherapy targeting hotspot driver mutations.

Hotspot driver mutations presented by human leukocyte antigens might be recognized by anti-tumor T cells. Based on their advantages of tumor-specificity and immunogenicity, neoantigens derived from hotspot mutations, such as PIK3CAH1047L, may serve as emerging targets for cancer immunotherapies. NetMHCpan V4.1 was utilized for predicting neoepitopes of PIK3CA hotspot mutation. Using in vitro stimulation, antigen-specific T cells targeting the HLA-A*11:01-restricted PIK3CA mutation were isolated from healthy donor-derived peripheral blood mononuclear cells. T cell receptors (TCRs) were cloned using single-cell PCR and sequencing. Their functionality was assessed through T cell activation markers, cytokine production and cytotoxic response to cancer cell lines pulsed with peptides or transduced genes of mutant PIK3CA. Immunogenic mutant antigens from PIK3CA and their corresponding CD8+ T cells were identified. These PIK3CA mutation-specific CD8+ T cells were subsequently enriched, and their TCRs were isolated. The TCR clones exhibited mutation-specific and HLA-restricted reactivity, demonstrating varying degrees of functional avidity. Identified TCR genes were transferred into CD8+ Jurkat cells and primary T cells deficient of endogenous TCRs. TCR-expressing cells demonstrated specific recognition and reactivity against the PIK3CAH1047L peptide presented by HLA-A*11:01-expressing K562 cells. Furthermore, mutation-specific TCR-T cells demonstrated an elevation in cytokine production and profound cytotoxic effects against HLA-A*11:01+ malignant cell lines harboring PIK3CAH1047L. Our data demonstrate the immunogenicity of an HLA-A*11:01-restricted PIK3CA hotspot mutation and its targeting therapeutic potential, together with promising candidates of TCR-T cell therapy.

Influence of early childhood parental hostility and socioeconomic stress on children's internalizing symptom trajectories from childhood to adolescence.

Introduction: Children and adolescents with elevated internalizing symptoms are at increased risk for depression, anxiety, and other psychopathology later in life. The present study examined the predictive links between two bioecological factors in early childhood-parental hostility and socioeconomic stress-and children's internalizing symptom class outcomes, while considering the effects of child sex assigned at birth on internalizing symptom development from childhood to adolescence. Materials and Methods: The study used a sample of 1,534 children to test the predictive effects of socioeconomic stress at ages 18 and 27 months; hostile parenting measured at child ages 4-5; and sex assigned at birth on children's internalizing symptom latent class outcomes at child ages 7-9, 10-12, 13-15, and 16-19. Analyses also tested the mediating effect of parenting on the relationship between socioeconomic stress and children's symptom classes. Other covariates included parent depressive symptoms at child ages 4-5 and child race and ethnicity. Results: Analyses identified three distinct heterogenous internalizing symptom classes characterized by relative symptom levels and progression: low (35%); moderate and increasing (41%); and higher and increasing (24%). As anticipated, higher levels of parental hostility in early childhood predicted membership in the higher and increasing symptom class, compared with the low symptom class (odds ratio (OR) = .61, 95% confidence interval (CI) [.48,.77]). Higher levels of early childhood socioeconomic stress were also associated with the likelihood of belonging to the higher-increasing symptom class compared to the low and moderate-increasing classes (OR = .46, 95% CI [.35,.60] and OR = .56, 95% CI [.44,.72], respectively). The total (c = .61) and direct (c' = .57) effects of socioeconomic stress on children's symptom class membership in the mediation analysis were significant (p <.001). Discussion: Study findings suggest that intervening on modifiable bioecological stressors-including parenting behaviors and socioeconomic stressors-may provide important protective influences on children's internalizing symptom trajectories.

Retinoic acid mitigates the NSC319726-induced spermatogenesis dysfunction through cuproptosis-independent mechanisms.

Copper ionophore NSC319726 has attracted researchers' attention in treating diseases, particularly cancers. However, its potential effects on male reproduction during medication are unclear. This study aimed to determine whether NSC319726 exposure affected the male reproductive system. The reproductive toxicity of NSC319726 was evaluated in male mice following a continuous exposure period of 5 weeks. The result showed that NSC319726 exposure caused testis index reduction, spermatogenesis dysfunction, and architectural damage in the testis and epididymis. The exposure interfered with spermatogonia proliferation, meiosis initiation, sperm count, and sperm morphology. The exposure also disturbed androgen synthesis and blood testis barrier integrity. NSC319726 treatment could elevate the copper ions in the testis to induce cuproptosis in the testis. Copper chelator rescued the elevated copper ions in the testis and partly restored the spermatogenesis dysfunction caused by NSC319726. NSC319726 treatment also decreased the level of retinol dehydrogenase 10 (RDH10), thereby inhibiting the conversion of retinol to retinoic acid, causing the inability to initiate meiosis. Retinoic acid treatment could rescue the meiotic initiation and spermatogenesis while not affecting the intracellular copper ion levels. The study provided an insight into the bio-safety of NSC319726. Retinoic acid could be a potential therapy for spermatogenesis impairment in patients undergoing treatment with NSC319726.

Mechanisms governing vesicle traffic at the Golgi apparatus.

Vesicle transport at the Golgi apparatus is a well-described process, and the major protein components involved have been identified. This includes the coat proteins that function in cargo sorting and vesicle formation, and the proteins that mediate the downstream events of vesicle tethering and membrane fusion. However, despite this knowledge, there remain significant gaps in our mechanistic understanding of these processes which includes how they are coordinated in space and time. In this review we discuss recent advances that have provided new insights into the mechanisms of Golgi trafficking, focussing on vesicle formation and cargo sorting, and vesicle tethering and fusion. These studies point to a high degree of spatial organisation of trafficking components at the Golgi and indicate an inherent plasticity of trafficking. Going forward, further advancements in technology and more sophisticated functional assays are expected to yield greater understanding of the mechanisms that govern Golgi trafficking events.

Unveiling the significance of inducible nitric oxide synthase: Its impact on cancer progression and clinical implications.

The intricate role of inducible nitric oxide synthase (iNOS) in cancer pathophysiology has garnered significant attention, highlighting the complex interplay between tumorigenesis, immune response, and cellular metabolism. As an enzyme responsible for producing nitric oxide (NO) in response to inflammatory stimuli. iNOS is implicated in various aspects of cancer development, including DNA damage, angiogenesis, and evasion of apoptosis. This review synthesizes the current findings from both preclinical and clinical studies on iNOS across different cancer types, reflecting the variability depending on cellular context and tumor microenvironment. We explore the molecular mechanisms by which iNOS modulates cancer cell growth, survival, and metastasis, emphasizing its impact on immune surveillance and response to treatment. Additionally, the potential of targeting iNOS as a therapeutic strategy in cancer treatment is examined. By integrating insights from recent advances, this review aims to elucidate the significant role of iNOS in cancer and pave the way for novel diagnostic and therapeutic approaches.

State of the art in self-sustaining smoldering for remediation of contaminated soil and disposal of organic waste.

Smoldering combustion applications in energy and environmental fields have attracted increasing research attention in recent years. Smoldering has demonstrated considerable green advantages, such as having a low carbon footprint and being sustainable, for remediation of organic-contaminated soil and disposal of high-moisture, low-calorific value, slurry-type organic waste due to its self-sustaining reaction characteristic. This review aims to analyze and summarize studies on smoldering applications to refine the critical components of applied smoldering systems, key reaction characteristics, and corresponding influencing conditions that affect their effectiveness. Furthermore, the common characteristics and influencing factors of different smoldering application scenarios are compared to provide a comprehensive reference for commercial applications. Thus, this paper specifically includes an overview of the impact of inert porous media, combustible material, and oxidants in applied smoldering systems; a review of the research status of the three key reaction characteristics, including peak temperature, smoldering front propagation velocity, and self-sustainability; a summary of typical influencing factors, disposal material characteristics, and control conditions in the two mainstream application directions, which are remediation of contaminated soil and disposal of organic waste; and a comparative analysis of the common modes of applied smoldering beyond the lab scale. As a technically effective and energy-efficient emerging technology, the prospects of smoldering as a robust treatment process in environmental pollution cleanup are presented.

Clinical characteristics and risk factors of post-operative intestinal flora disorder following laparoscopic colonic surgery: A propensity-score-matching analysis.

BACKGROUND: Intestinal flora disorder (IFD) poses a significant challenge after laparoscopic colonic surgery, and no standard criteria exists for its diagnosis and treatment. AIM: To analyze the clinical features and risk factors of IFD. METHODS: Patients with colon cancer receiving laparoscopic surgery were included using propensity-score-matching (PSM) methods. Based on the occurrence of IFD, patients were categorized into IFD and non-IFD groups. The clinical characteristics and treatment approaches for patients with IFD were analyzed. Multivariate regression analysis was performed to identify the risk factors of IFD. RESULTS: The IFD incidence after laparoscopic surgery was 9.0% (97 of 1073 patients). After PSM, 97 and 194 patients were identified in the IFD and non-IFD groups, respectively. The most common symptoms of IFD were diarrhea and abdominal, typically occurring on post-operative days 3 and 4. All patients were managed conservatively, including modulation of the intestinal flora (90.7%), oral/intravenous application of vancomycin (74.2%), and insertion of a gastric/ileus tube for decompression (23.7%). Multivariate regression analysis identified that pre-operative intestinal obstruction [odds ratio (OR) = 2.79, 95%CI: 1.04-7.47, P = 0.041] and post-operative antibiotics (OR = 8.57, 95%CI: 3.31-23.49, P < 0.001) were independent risk factors for IFD, whereas pre-operative parenteral nutrition (OR = 0.12, 95%CI: 0.06-0.26, P < 0.001) emerged as a protective factor. CONCLUSION: A stepwise approach of probiotics, vancomycin, and decompression could be an alternative treatment for IFD. Special attention is warranted post-operatively for patients with pre-operative obstruction or early use of antibiotics.

Heat stress-induced dysbiosis of the gut microbiota impairs spermatogenesis by regulating secondary bile acid metabolism in the gut.

Heat stress (HS) poses a substantial challenge to livestock. Studies have demonstrated that HS reduces fertility and leads to gut microbiota dysbiosis in bulls. However, the impact of the gut microbiota on fertility in bulls during HS is still unclear. Our research revealed that HS exposure decreased semen quality in bulls, and fecal microbiota transplantation (FMT) from heat-stressed bulls to recipient mice resulted in a significant decrease in number of testicular germ cells and epididymal sperm. Untargeted metabolomics methodology and 16S rDNA sequencing conjoint analysis revealed that Akkermansia muciniphila (A. muciniphila) seemed to be a key bacterial regulator of spermatogenesis after HS exposure. Moreover, the research indicated that A. muciniphila regulated secondary bile acid metabolism by promoting the colonization of bile salt hydrolase (BSH)-metabolizing bacteria, leading to increase of retinol absorption in the host gut and subsequently elevation of testicular retinoic acid level, thereby improving spermatogenesis. This study sheds light on the relationship between HS-induced microbiota dysbiosis and spermatogenesis, offering a potential therapeutic approach for addressing bull spermatogenic dysfunction triggered by HS exposure.

COL5A1 promotes triple-negative breast cancer progression by activating tumor cell-macrophage crosstalk.

Triple-negative breast cancer (TNBC) is an exceptionally aggressive subtype of breast cancer. Despite the recognized interplay between tumors and tumor-associated macrophages in fostering drug resistance and disease progression, the precise mechanisms leading these interactions remain elusive. Our study revealed that the upregulation of collagen type V alpha 1 (COL5A1) in TNBC tissues, particularly in chemoresistant samples, was closely linked to an unfavorable prognosis. Functional assays unequivocally demonstrated that COL5A1 played a pivotal role in fueling cancer growth, metastasis, and resistance to doxorubicin, both in vitro and in vivo. Furthermore, we found that the cytokine IL-6, produced by COL5A1-overexpressing TNBC cells actively promoted M2 macrophage polarization. In turn, TGFß from M2 macrophages drived TNBC doxorubicin resistance through the TGFß/Smad3/COL5A1 signaling pathway, establishing a feedback loop between TNBC cells and macrophages. Mechanistically, COL5A1 interacted with TGM2, inhibiting its K48-linked ubiquitination-mediated degradation, thereby enhancing chemoresistance and increasing IL-6 secretion. In summary, our findings underscored the significant contribution of COL5A1 upregulation to TNBC progression and chemoresistance, highlighting its potential as a diagnostic and therapeutic biomarker for TNBC.

Mendelian randomization of circulating proteome identifies IFN-γ as a druggable target in aplastic anemia.

BACKGROUND: Aplastic anemia (AA) is a kind of bone marrow failure (BMF) characterized by pancytopenia with hypoplasia/aplasia of bone marrow. Immunosuppressive therapy and bone marrow transplantation are effective methods to treat severe aplastic anemia. However, the efficacy is limited by complications and the availability of suitable donors. This study aimed to determine whether any circulating druggable protein levels may have causal effects on AA and provide potential novel drug targets for AA. METHODS: Genetic variants strongly associated with circulating druggable protein levels to perform Mendelian randomization (MR) analyses were used. The effect of these druggable protein levels on AA risk was measured using the summary statistics from a large-scale proteomic genome-wide association study (GWAS) and FinnGen database ( https://www.finngen.fi/en/access_results ). Multivariable MR analyses were performed to statistically adjust for potential confounders, including platelet counts, reticulocyte counts, neutrophil counts, and proportions of hematopoietic stem cells. RESULTS: The data showed that higher level of circulating IFN-γ levels was causally associated with AA susceptibility. The causal effects of circulating IFN-γ levels on the AA were broadly consistent, when adjusted for platelet counts, reticulocyte counts, neutrophil counts and proportions of hematopoietic stem cells. CONCLUSIONS: High levels of circulating IFN-γ levels might increase the risk of AA and might provide a potential novel target for AA.

Current challenges and therapeutic advances of CAR-T cell therapy for solid tumors.

The application of chimeric antigen receptor (CAR) T cells in the management of hematological malignancies has emerged as a noteworthy therapeutic breakthrough. Nevertheless, the utilization and effectiveness of CAR-T cell therapy in solid tumors are still limited primarily because of the absence of tumor-specific target antigen, the existence of immunosuppressive tumor microenvironment, restricted T cell invasion and proliferation, and the occurrence of severe toxicity. This review explored the history of CAR-T and its latest advancements in the management of solid tumors. According to recent studies, optimizing the design of CAR-T cells, implementing logic-gated CAR-T cells and refining the delivery methods of therapeutic agents can all enhance the efficacy of CAR-T cell therapy. Furthermore, combination therapy shows promise as a way to improve the effectiveness of CAR-T cell therapy. At present, numerous clinical trials involving CAR-T cells for solid tumors are actively in progress. In conclusion, CAR-T cell therapy has both potential and challenges when it comes to treating solid tumors. As CAR-T cell therapy continues to evolve, further innovations will be devised to surmount the challenges associated with this treatment modality, ultimately leading to enhanced therapeutic response for patients suffered solid tumors.

SIRT3 regulates cardiolipin biosynthesis in pressure overload-induced cardiac remodeling by PPARγ-mediated mechanism.

Cardiac remodeling is the primary pathological feature of chronic heart failure (HF). Exploring the characteristics of cardiac remodeling in the very early stages of HF and identifying targets for intervention are essential for discovering novel mechanisms and therapeutic strategies. Silent mating type information regulation 2 homolog 3 (SIRT3), as a major mitochondrial nicotinamide adenine dinucleotide (NAD)-dependent deacetylase, is required for mitochondrial metabolism. However, whether SIRT3 plays a role in cardiac remodeling by regulating the biosynthesis of mitochondrial cardiolipin (CL) is unknown. In this study, we induced pressure overload in wild-type (WT) and SIRT3 knockout (SIRT3-/-) mice via transverse aortic constriction (TAC). Compared with WT mouse hearts, the hearts of SIRT3-/- mice exhibited more-pronounced cardiac remodeling and fibrosis, greater reactive oxygen species (ROS) production, decreased mitochondrial-membrane potential (ΔΨm), and abnormal mitochondrial morphology after TAC. Furthermore, SIRT3 deletion aggravated TAC-induced decrease in total CL content, which might be associated with the downregulation of the CL synthesis related enzymes cardiolipin synthase 1 (CRLS1) and phospholipid-lysophospholipid transacylase (TAFAZZIN). In our in vitro experiments, SIRT3 overexpression prevented angiotensin II (AngII)- induced aberrant mitochondrial function, CL biosynthesis disorder, and peroxisome proliferator-activated receptor gamma (PPARγ) downregulation in cardiomyocytes; meanwhile, SIRT3 knockdown exacerbated these effects. Moreover, the addition of GW9662, a PPARγ antagonist, partially counteracted the beneficial effects of SIRT3 overexpression. In conclusion, SIRT3 regulated PPARγ-mediated CL biosynthesis, maintained the structure and function of mitochondria, and thereby protected the myocardium against cardiac remodeling.

Medical equipment effectiveness evaluation model based on cone-constrained DEA and attention-based bi-LSTM.

This study constructs a composite indicator system covering the core dimensions of medical equipment input and output. Based on this system, an innovative cone-constrained data envelopment analysis (DEA) model is designed. The model integrates the advantages of the analytic hierarchy process (AHP) with an improved criterion importance through intercriteria correlation (CRITIC) method to determine subjective and objective weights and employs game theory to obtain the final combined weights, which are further incorporated as constraints to form the cone-constrained DEA model. Finally, a bidirectional long short-term memory (Bi-LSTM) model with an attention mechanism is introduced for integration, aiming to provide a novel and practical model for evaluating the effectiveness of medical equipment. The proposed model has essential reference value for optimizing medical equipment management decision-making and investment strategies.

Correlation between fat-to-muscle mass ratio and cognitive impairment in elderly patients with type 2 diabetes mellitus: a cross-sectional study.

BACKGROUND: Fat to muscle mass ratio (FMR), a novel index integrating fat and muscle composition, has garnered attention in age-related conditions such as type 2 diabetes mellitus (T2DM) and neurodegenerative diseases. Despite this research on the relationship between FMR and cognitive impairment (CI) in T2DM remains scarce. This study aimed to investigate the sex-specific association between FMR and CI in elderly T2DM patients. METHODS: A total of 768 elderly (> 60 years) T2DM in-patients (356 men and 412 women) were recruited from the Department of Endocrinology at Tianjin Nankai University affiliated hospital. Bioelectrical Impedance Analysis (BIA) was used to assess body composition, and Montreal Cognitive Assessment (MoCA) was used to evaluate cognitive performance. T2DM patients were categorized into normal cognitive function (NC) and cognitive impairment (CI) groups based on MoCA scores and stratified by sex. Binary logistic regression was employed to examine the association between FMR and CI. RESULTS: Among the participants, 42.7% of men and 56.3% of women experienced cognitive deterioration. Women with CI exhibited lower body mass index (BMI) and skeletal muscle mass index (SMI), while men with cognitive disorders showed lower SMI, FMR, and higher fat mass index (FMI). FMR was consistently unrelated to cognition in females, irrespective of adjustment made. However, in males, FMR was significantly associated with an increasing risk of cognitive dysfunction after adjusting for demographic and clinical variables (OR: 1.175, 95% CI: 1.045-1.320, p = 0.007). Furthermore, for each 0.1 increase in FMR, the incidence of CI rose by 31.1% after additional adjustment for BMI. In males, the prevalence of CI increased sequentially across FMR quartiles (p < 0.05). CONCLUSION: Elderly T2DM men with high FMR had unfavorable cognitive function. FMR is independently associated with an increased risk of CI in male T2DM patients regardless of BMI.

The Renoprotective and Anti-Inflammatory Effects of Human Urine-Derived Stem Cells on Acute Kidney Injury Animals.

BACKGROUND: Acute Kidney Injury (AKI) is defined as a sudden loss of kidney function, which is often caused by drugs, toxins, and infections. The large spectrum of AKI implies diverse pathophysiological mechanisms. In many cases, AKI can be lethal, and kidney replacement therapy is frequently needed. However, current treatments are not satisfying. Developing novel therapies for AKI is essential. Adult stem cells possess regenerative ability and play an important role in medical research and disease treatment. METHODS: In this study, we isolated and characterized a distinct human urine-derived stem cell, which expressed both proximal tubular cell and mesenchymal stem cell genes as well as certain unique genes. RESULTS: It was found that these cells exhibited robust protective effects on tubular cells and anti- inflammatory effects on macrophages in vitro. In an ischemia-reperfusion-induced acute kidney injury NOD-SCID mouse model, transplantation of USCs significantly protected the kidney morphology and functions in vivo. CONCLUSION: In summary, our results highlighted the effectiveness of USCs in protecting from PTC injury and impeding macrophage polarization, as well as the secretion of pro-inflammatory interleukins, suggesting the potential of USCs as a novel cell therapy in AKI.

Study on the optimal elastic modulus of flexible blades for right heart assist device supporting patients with single-ventricle physiologies.

Background: Patients with single-ventricle physiologies continue to experience insufficient circulatory power after undergoing palliative surgeries. This paper proposed a right heart assist device equipped with flexible blades to provide circulatory assistance for these patients. The optimal elastic modulus of the flexible blades was investigated through numerical simulation. Methods: A one-way fluid-structure interaction (FSI) simulation was employed to study the deformation of flexible blades during rotation and its impact on device performance. The process began with a computational fluid dynamics (CFD) simulation to calculate the blood pressure rise and the pressure on the blades' surface. Subsequently, these pressure data were exported for finite element analysis (FEA) to compute the deformation of the blades. The fluid domain was then recreated based on the deformed blades' shape. Iterative CFD and FEA simulations were performed until both the blood pressure rise and the blades' shape stabilized. The blood pressure rise, hemolysis risk, and thrombosis risk corresponding to blades with different elastic moduli were exhaustively evaluated to determine the optimal elastic modulus. Results: Except for the case at 8,000 rpm with a blade elastic modulus of 40 MPa, the pressure rise associated with flexible blades within the studied range (rotational speeds of 4,000 rpm and 8,000 rpm, elastic modulus between 10 MPa and 200 MPa) was lower than that of rigid blades. It was observed that the pressure rise corresponding to flexible blades increased as the elastic modulus increased. Additionally, no significant difference was found in the hemolysis risk and thrombus risk between flexible blades of various elastic moduli and rigid blades. Conclusion: Except for one specific case, deformation of the flexible blades within the studied range led to a decrease in the impeller's functionality. Notably, rotational speed had a more significant impact on hemolysis risk and thrombus risk compared to blade deformation. After a comprehensive analysis of blade compressibility, blood pressure rise, hemolysis risk, and thrombus risk, the optimal elastic modulus for the flexible blades was determined to be between 40 MPa and 50 MPa.