Photocatalytic Multisite Functionalization of Unactivated Terminal Alkenes by Merging Polar Cycloaddition and Radical Ring-Opening Process.

Although highly appealing for rapid access of molecular complexity, multi-functionalization of alkenes that allows incorporation of more than two functional groups remains a prominent challenge. Herein, we report a novel strategy that merges dipolar cycloaddition with photoredox promoted radical ring-opening remote C(sp3)-H functionalization, thus enabling a smooth 1,2,5-trifunctionalization of unactivated alkenes. A highly regioselective [3+2] cycloaddition anchors a reaction trigger onto alkene substrates. The subsequent halogen atom transfer (XAT) selectively initiates ring-opening process, which is followed by a series of 1,5-hydrogen atom transfer (1,5-HAT) and intermolecular fluorine atom transfer (FAT) events. With this method, site-selective introduction of three different functional groups is accomplished and a broad spectrum of valuable ß-hydroxyl-ε-fluoro-nitrile products are synthesized from readily available terminal alkenes.

Visible light-induced chemoselective 1,2-diheteroarylation of alkenes.

Visible-light photocatalysis has evolved as a powerful technique to enable controllable radical reactions. Exploring unique photocatalytic mode for obtaining new chemoselectivity and product diversity is of great significance. Herein, we present a photo-induced chemoselective 1,2-diheteroarylation of unactivated alkenes utilizing halopyridines and quinolines. The ring-fused azaarenes serve as not only substrate, but also potential precursors for halogen-atom abstraction for pyridyl radical generation in this photocatalysis. As a complement to metal catalysis, this photo-induced radical process with mild and redox neutral conditions assembles two different heteroaryl groups into alkenes regioselectively and contribute to broad substrates scope. The obtained products containing aza-arene units permit various further diversifications, demonstrating the synthetic utility of this protocol. We anticipate that this protocol will trigger the further advancement of photo-induced alkyl/aryl halides activation.

Beta cells deficient for Renalase counteract autoimmunity by shaping natural killer cell activity.

Type 1 diabetes (T1D) arises from autoimmune-mediated destruction of insulin-producing pancreatic beta cells. Recent advancements in the technology of generating pancreatic beta cells from human pluripotent stem cells (SC-beta cells) have facilitated the exploration of cell replacement therapies for treating T1D. However, the persistent threat of autoimmunity poses a significant challenge to the survival of transplanted SC-beta cells. Genetic engineering is a promising approach to enhance immune resistance of beta cells as we previously showed by inactivating the Renalase (Rnls) gene. Here, we demonstrate that Rnls loss of function in beta cells shapes autoimmunity by mediating a regulatory natural killer (NK) cell phenotype important for the induction of tolerogenic antigen-presenting cells. Rnls-deficient beta cells mediate cell-cell contact-independent induction of hallmark anti-inflammatory cytokine Tgfß1 in NK cells. In addition, surface expression of regulatory NK immune checkpoints CD47 and Ceacam1 is markedly elevated on beta cells deficient for Rnls. Altered glucose metabolism in Rnls mutant beta cells is involved in the upregulation of CD47 surface expression. These findings are crucial to better understand how genetically engineered beta cells shape autoimmunity, giving valuable insights for future therapeutic advancements to treat and cure T1D.

Finite element simulation of treatment with locking plate for distal fibula fractures.

An improved Finite Element Model(FEM) is applied to compare the biomechanical stability of plates with three different options in the treatment of distal fibula fractures in this study. The Computed Tomography(CT) scan of the knee to ankle segment of a volunteer was performed. A 3D fibula FEM was reconstructed based on the CT data. Three different loads (uni-pedal standing, torsion, and twisting) were applied, the same as in the experiments in the literature. The stresses and strains of the three options were compared under the same loads, using a 4-hole locking plate (Option A), a 5-hole locking plate (Option B), and a 6-hole locking plate (Option C) in a standard plate for lateral internal fixation. The simulation results show that all three options showed a stress masking effect. Option C had the best overall biomechanical performance and could effectively distribute the transferred weight. This is because option C has greater torsional stiffness and better biomechanical stability than options A and B, and therefore, option C is the recommended internal fixation method for distal fibula fractures. The Finite Element Analysis(FEA) method developed in this work applies to the stress analysis of fracture treatment options in other body parts.

Orientation selectivity mapping in the visual cortex.

The orientation map is one of the most well-studied functional maps of the visual cortex. However, results from the literature are of different qualities. Clear boundaries among different orientation domains and blurred uncertain distinctions were shown in different studies. These unclear imaging results will lead to an inaccuracy in depicting cortical structures, and the lack of consideration in experimental design will also lead to biased depictions of the cortical features. How we accurately define orientation domains will impact the entire field of research. In this study, we test how spatial frequency (SF), stimulus size, location, chromatic, and data processing methods affect the orientation functional maps (including a large area of dorsal V4, and parts of dorsal V1) acquired by intrinsic signal optical imaging. Our results indicate that, for large imaging fields, large grating stimuli with mixed SF components should be considered to acquire the orientation map. A diffusion model image enhancement based on the difference map could further improve the map quality. In addition, the similar outcomes of achromatic and chromatic gratings indicate two alternative types of afferents from LGN, pooling in V1 to generate cue-invariant orientation selectivity.

Death-Associated Protein-1 Plays a Role in the Reproductive Development of Nilaparvata lugens and the Transovarial Transmission of Its Yeast-Like Symbiont.

Death-associated protein-1 (DAP-1) plays a crucial role in cell growth, migration, autophagy, and apoptosis in mammals. However, its function in insects remains unclear. In the present study, we cloned and identified Nilaparvata lugens DAP-1 (NlDAP-1). NlDAP-1 was expressed during all developmental stages and in all tissues of N. lugens, being particularly higher in the ovaries of female adults. RNAi with double-stranded NlDAP-1 RNA significantly inhibited the expression of NlDAP-1, leading to premature death (dying seven days earlier), delayed ovarian development, and fewer offspring (76.7% reduction in eggs with 77.4% reduction in egg hatching rate). Additionally, an immunofluorescence experiment showed that NlDAP-1 was highly expressed when yeast-like symbionts (YLSs) entered N. lugens oocytes, and inhibiting the expression of NlDAP-1 disturbed the process; the RNAi of NlDAP-1 caused a 34.9% reduction in the YLSs that entered oocytes. These results indicate that NlDAP-1 plays a crucial role in the reproductive development of N. lugens and the transovarial transmission of its YLSs.

Tetramethylpyrazine nitrone delays the aging process of C. elegans by improving mitochondrial function through the AMPK/mTORC1 signaling pathway.

Aging is characterized as the process of functional decline in an organism from adulthood, often marked by a progressive loss of cellular function and systemic deterioration of multiple tissues. Among the numerous molecular, cellular, and systemic hallmarks associated with aging, mitochondrial dysfunction is considered one of the pivotal factors that initiates the aging process. During aging, mitochondria undergo varying degrees of damage, resulting in impaired energy production and disruption of the homeostatic regulation of mitochondrial quality control systems, which in turn affects cellular energy metabolism and results in cellular dysfunction, accelerating the aging process. AMP-activated protein kinase (AMPK) and the mechanistic target of rapamycin complex 1 (mTORC1) are two central kinase complexes responsible for sensing intracellular nutrient levels, regulating metabolic homeostasis, modulating aging and play a crucial role in maintaining the homeostatic balance of mitochondria. Our previous studies found that the novel compound tetramethylpyrazine nitrone (TBN) can protect mitochondria via the AMPK/mTOR pathway in many animal models, extending healthy lifespan through the Nrf2 signaling pathway in nematodes. Building upon this foundation, we have posited a reasonable hypothesis, TBN can improve mitochondrial function to delay aging by regulating the AMPK/mTORC1 signaling pathway. This study focuses on the C. elegans, exploring the impact and underlying mechanisms of TBN on aging and mitochondrial function (especially the mitochondrial quality control system) during the aging process. The present studies demonstrated that TBN extends lifespan of wild-type nematodes and is associated with the AMPK/mTORC1 signaling pathway. TBN elevated ATP and NAD+ levels in aging nematodes while orchestrating mitochondrial biogenesis and mitophagy. Moreover, TBN was observed to significantly enhance normal activities during aging in C. elegans, such as mobility and pharyngeal pumping, concurrently impeding lipofuscin accumulation that were closely associated with AMPK and mTORC1. This study not only highlights the delayed effects of TBN on aging but also underscores its potential application in strategies aimed at improving mitochondrial function via the AMPK/mTOR pathway in C. elegans.

Renalase inhibition regulates ß cell metabolism to defend against acute and chronic stress.

Renalase (Rnls), annotated as an oxidase enzyme, is a GWAS gene associated with Type 1 Diabetes (T1D) risk. We previously discovered that Rnls inhibition delays diabetes onset in mouse models of T1D in vivo , and protects pancreatic ß cells against autoimmune killing, ER and oxidative stress in vitro . The molecular biochemistry and functions of Rnls are entirely uncharted. Here we find that Rnls inhibition defends against loss of ß cell mass and islet dysfunction in chronically stressed Akita mice in vivo . We used RNA sequencing, untargeted and targeted metabolomics and metabolic function experiments in mouse and human ß cells and discovered a robust and conserved metabolic shift towards glycolysis, amino acid abundance and GSH synthesis to counter protein misfolding stress, in vitro . Our work illustrates a function for Rnls in mammalian cells, and suggests an axis by which manipulating intrinsic properties of ß cells can rewire metabolism to protect against diabetogenic stress.

The relationship between landscape pattern and plant species diversity in east Dongting lake wetland based on different Eco-environment.

Exploring the impact factors associated with biodiversity and the relationship between them has always been a concerned issue in recent years. However, the previous research mostly focus on theoretical layer. Accordingly, the relationship between landscape pattern and biodiversity is to be analyzed in this research. The landscape pattern determines the function and ecological process of the landscape, and affects the species flow, information flow and energy flow in the landscape. Land use patterns has inevitably left an impact on the landscape pattern. Landscape pattern determines the function and ecological process of landscape and thus plays a significant role in biodiversity. East Dongting Lake National Nature Reserve is taken as the research object of the paper, and the remote sensing image data of three different time periods are collected, including 2000, 2010 and 2020. With an interpretation of the vegetation landscape pattern changes inside the protected area to collect and analyze the vegetation coverage. By comparing landscape patterns and the dynamic changes of land use in different periods of time, the correlation between landscape pattern characteristics and regional biodiversity is to be analyzed. Research shows: (1) From 2000 to 2020, the vegetation coverage of East Dongting Lake increased, but the landscape shape, scale, diversity and uniformity index decreased to varying degrees. (2) At the class level of landscape type, the relationship between landscape index and biodiversity is different. A complex relationship between farmland landscape and biodiversity. There is a significant positive correlation between the index of grassland landscape type and the index of regional biodiversity. (3) The correlation analysis results at the landscape level show that the landscape characteristic index is positively correlated with the regional biodiversity index. The grassland landscape in the area is the main habitat of biological species. At the same time, as the main grain producing area, the impact of farmland landscape cannot be ignored. This study has certain theoretical guiding significance for the protection and management of biodiversity in the region in terms of maintaining landscape pattern in particular the grassland landscape area and increasing vegetation coverage in the process of land use.

Streptomyces camelliae sp. nov., isolated from rhizosphere soil of Camellia oleifera Abel.

A novel actinobacterium strain, designated HUAS 2-6 T, was isolated from the rhizosphere soil of Camellia oleifera Abel collected from Taoyuan County, Northwestern Hunan Province, South China. This strain was subjected to a polyphasic taxonomic study. Strain HUAS 2-6 T is characterized by morphology typical of members of the genus Streptomyces, with deep purplish vinaceous aerial mycelia and deep dull lavender substrate mycelia. Strain HUAS 2-6 T, based on the full-length 16S rRNA gene sequence analysis, exhibited the highest similarities to S. puniciscabiei S77T (99.31%), S. filipinensis NBRC 12860 T (99.10%), S. yaanensis CGMCC 4.7035 T (99.09%), S. fodineus TW1S1T (99.08%), S. broussonetiae CICC 24819 T (98.76%), S. achromogenes JCM 4121 T (98.69%), S. barringtoniae JA03T (98.69%), and less than 98.70% with other validly species. In phylogenomic tree, strain HUAS 2-6 T was clustered together with S. broussonetiae CICC 24819 T, suggesting that they were closely related to each other. However, average nucleotide identity (ANI) and digital DNA-DNA hybridisation (dDDH) between them were much less than the species cutoff values (ANI 96.7% and dDDH 70%). Moreover, in phenotypic and chemotaxonomic characteristics, strain HUAS 2-6 T is distinct from S. broussonetiae CICC 24819 T. On the basis of the polyphasic data, strain HUAS 2-6 T is proposed to represent a novel species, Streptomyces camelliae sp. nov. (= MCCC 1K04729T = JCM 35918 T).

Strictosamide promotes wound healing through activation of the PI3K/AKT pathway.

Nauclea officinalis, as a Chinese medicine in Hainan province, had the effect of treating lower limb ulcers, burn infections. In this paper, we studied the effect of Strictosamide (STR), the main bioactive compound in Nauclea officinals, on wound healing and explored its internal mechanism. Firstly, the wound healing potential of STR was evaluated in a rat model, demonstrating its ability to expedite wound healing, mitigate inflammatory infiltration, and enhance collagen deposition. Additionally, immunofluorescence analysis revealed that STR up-regulated the expression of CD31 and PCNA. Subsequently, target prediction, protein-protein interaction (PPI), gene ontology (GO), and pathway enrichment analyses were used to obtain potential targets, specific biological processes, and molecular mechanisms of STR for the potential treatment of wound healing. Furthermore, molecular docking was conducted to predict the binding affinity between STR and its associated targets. Additionally, in vivo and in vitro experiments confirmed that STR could increase the expression of P-PI3K, P-AKT and P-mTOR by activating the PI3K/AKT signaling pathway. In summary, this study provided a new explanation for the mechanism by which STR promotes wound healing through network pharmacology, suggesting that STR may be a new candidate for treating wound.

Engineered endolysin of Klebsiella pneumoniae phage is a potent and broad-spectrum bactericidal agent against "ESKAPEE" pathogens.

The rise of antimicrobial resistance in ESKAPEE pathogens poses significant clinical challenges, especially in polymicrobial infections. Bacteriophage-derived endolysins offer promise in combating this crisis, but face practical hurdles. Our study focuses on engineering endolysins from a Klebsiella pneumoniae phage, fusing them with ApoE23 and COG133 peptides. We assessed the resulting chimeric proteins' bactericidal activity against ESKAPEE pathogens in vitro. ApoE23-Kp84B (CHU-1) reduced over 3 log units of CFU for A. baumannii, E. faecalis, K. pneumoniae within 1 h, while COG133-Kp84B (CHU-2) showed significant efficacy against S. aureus. COG133-L1-Kp84B, with a GS linker insertion in CHU-2, exhibited outstanding bactericidal activity against E. cloacae and P. aeruginosa. Scanning electron microscopy revealed alterations in bacterial morphology after treatment with engineered endolysins. Notably, CHU-1 demonstrated promising anti-biofilm and anti-persister cell activity against A. baumannii and E. faecalis but had limited efficacy in a bacteremia mouse model of their coinfection. Our findings advance the field of endolysin engineering, facilitating the customization of these proteins to target specific bacterial pathogens. This approach holds promise for the development of personalized therapies tailored to combat ESKAPEE infections effectively.

Mogroside V reduced the excessive endoplasmic reticulum stress and mitigated the Ulcerative colitis induced by dextran sulfate sodium in mice.

Ulcerative colitis (UC) is an idiopathic, chronic inflammatory condition of the colon, characterized by repeated attacks, a lack of effective treatment options, and significant physical and mental health complications for patients. The endoplasmic reticulum (ER) is a vital intracellular organelle in maintaining cellular homeostasis. Endoplasmic reticulum stress (ERS) is induced when the body is exposed to adverse external stimuli. Numerous studies have shown that ERS-induced apoptosis plays a vital role in the pathogenesis of UC. Mogroside V (MV), an active ingredient of Monk fruit, has demonstrated excellent anti-inflammatory and antioxidant effects. In this study, we investigated the therapeutic effects of MV on dextran sulfate sodium (DSS)-induced UC and its potential mechanisms based on ERS. The results showed that MV exerted a protective effect against DSS-induced UC in mice as reflected by reduced DAI scores, increased colon length, reduced histological scores of the colon, and levels of pro-inflammatory cytokines, as well as decreased intestinal permeability. In addition, the expression of ERS pathway including BIP, PERK, eIF2α, ATF4, CHOP, as well as the apoptosis-related protein including Caspase-12, Bcl-2 and Bax, was found to be elevated in UC. However, MV treatment significantly inhibited the UC and reversed the expression of inflammation signaling pathway including ERS and ERS-induced apoptosis. Additionally, the addition of tunicamycin (Tm), an ERS activator, significantly weakened the therapeutic effect of MV on UC in mice. These findings suggest that MV may be a therapeutic agent for the treatment of DSS-induced UC by inhibiting the activation of the ERS-apoptosis pathway, and may provide a novel avenue for the treatment of UC.

Loss-of-function of ALDH3B2 transdifferentiates human pancreatic duct cells into beta-like cells.

Replenishment of pancreatic beta cells is a key to the cure for diabetes. Beta cells regeneration is achieved predominantly by self-replication especially in rodents, but it was also shown that pancreatic duct cells can transdifferentiate into beta cells. How pancreatic duct cells undergo transdifferentiated and whether we could manipulate the transdifferentiation to replenish beta cell mass is not well understood. Using a genome-wide CRISPR screen, we discovered that loss-of-function of ALDH3B2 is sufficient to transdifferentiate human pancreatic duct cells into functional beta-like cells. The transdifferentiated cells have significant increase in beta cell marker genes expression, secrete insulin in response to glucose, and reduce blood glucose when transplanted into diabetic mice. Our study identifies a novel gene that could potentially be targeted in human pancreatic duct cells to replenish beta cell mass for diabetes therapy.

Low remnant cholesterol and the subsequent risk of new-onset atrial fibrillation: A prospective cohort study.

BACKGROUND: Atrial fibrillation (AF) is a common arrhythmia with high morbidity and mortality implications. Several studies have described a paradoxical inverse relationship between serum cholesterol and the risk of AF, but it remains unknown whether remnant cholesterol (RC) is associated with AF incidence. OBJECTIVE: This study aims to prospectively investigate the association between RC and AF. METHODS: A total of 392,783 participants free of AF at baseline from the UK Biobank were included for the analysis. Cox proportional hazards model, subgroup analysis, and sensitivity analyses were used to evaluate the independent association between RC levels and the risk of new-onset AF. Furthermore, we performed a discordance analysis by using the median cutoff points of low-density lipoprotein cholesterol (LDL-C) and RC. RESULTS: After a median follow-up of 12.8 years (interquartile range 12.0-13.6 years), a total of 23,558 participants experienced incident AF. Compared with the highest RC level, the lower RC level was associated with an increased risk of AF incidence (quartile 1 vs quartile 4: hazard ratio 1.396; 95% confidence interval [CI] 1.343-1.452). The results remained robust across a series of sensitivity analyses. In the discordance analyses, a significantly higher risk of AF was observed in participants with discordant low RC/high LDL-C levels than in those with concordant high RC/LDL-C levels. In the low LDL-C group, RC reduction even contributed to an additional 15.8% increased rate of incident AF (low RC/low LDL-C: hazard ratio 1.303; 95% CI 1.260-1.348 vs high RC/low LDL-C: hazard ratio 1.125; 95% CI 1.079-1.172). CONCLUSION: Low RC levels were associated with an increased risk of incident AF independent of traditional cardiovascular risk factors.

Exploring the Localization of Siderophore-Mediated Cargo Delivery in Gram-Negative Bacteria Using 3-Hydroxypyridin-4(1H)-one-Fluorescein Probes.

The design of siderophore-antibiotic conjugates is a promising strategy to overcome drug resistance in negative bacteria. However, accumulating studies have shown that only those antibiotics acting on the cell wall or cell membrane multiply their antibacterial effects when coupled with siderophores, while antibiotics acting on targets in the cytoplasm of bacteria do not show an obvious enhancement of their antibacterial effects when coupled with siderophores. To explore the causes of this phenomenon, we synthesized several conjugate probes using 3-hydroxypyridin-4(1H)-ones as siderophores and replacing the antibiotic cargo with 5-carboxyfluorescein (5-FAM) or malachite green (MG) cargo. By monitoring changes in the fluorescence intensity of FAM conjugate 20 in bacteria, the translocation of the conjugate across the outer membranes of Gram-negative pathogens was confirmed. Further, the use of the fluorogen activating protein(FAP)/MG system revealed that 3-hydroxypyridin-4(1H)-one-MG conjugate 26 was ultimately distributed mainly in the periplasm rather than being translocated into the cytosol of Escherichia coli and Pseudomonas aeruginosa PAO1. Additional mechanistic studies suggested that the uptake of the conjugate involved the siderophore-dependent iron transport pathway and the 3-hydroxypyridin-4(1H)-ones siderophore receptor-dependent mechanism. Meanwhile, we demonstrated that the conjugation of 3-hydroxypyridin-4(1H)-ones to the fluorescein 5-FAM can reduce the possibility of the conjugates crossing the membrane layers of mammalian Vero cells by passive diffusion, and the advantages of the mono-3-hydroxypyridin-4(1H)-ones as a delivery vehicle in the design of conjugates compared to the tri-3-hydroxypyridin-4(1H)-ones. Overall, this work reveals the localization rules of 3-hydroxypyridin-4(1H)-ones as siderophores to deliver the cargo into Gram-negative bacteria. It provides a theoretical basis for the subsequent design of siderophore-antibiotic conjugates, especially based on 3-hydroxypyridin-4(1H)-ones as siderophores.

Wide-Size Range and High Robustness Self-Assembly Micropillars for Capturing Microspheres.

Capillary force driven self-assembly micropillars (CFSA-MP) holds immense promise for the manipulation and capture of cells/tiny objects, which has great demands of wide size range and high robustness. Here, we propose a novel method to fabricate size-adjustable and highly robust CFSA-MP that can achieve wide size range and high stability to capture microspheres. First, we fabricate a microholes template with an adjustable aspect ratio using the spatial-temporal shaping femtosecond laser double-pulse Bessel beam-assisted chemical etching technique, and then the micropillars with adjustable aspect ratio are demolded by polydimethylsiloxane (PDMS). We fully demonstrated the advantages of the Bessel optical field by using the spatial-temporal shaping femtosecond laser double-pulse Bessel beams to broaden the height range of the micropillars, which in turn expands the size range of the captured microspheres, and finally achieving a wide range of capturing microspheres with a diameter of 5-410 µm. Based on the inverted mold technology, the PDMS micropillars have ultrahigh mechanical robustness, which greatly improves the durability. CFSA-MP has the ability to capture tiny objects with wide range and high stability, which indicates great potential applications in the fields of chemistry, biomedicine, and microfluidics.

Formation of cation bridges and its promoting mechanism for sorption of sulfamethoxazole by montmorillonite.

The coexistence of metal cations is often accompanied by organic pollution and could affect the environmental fate of organics by mediating the formation of cation bridges. However, the environmental fate and risk of organics in cation co-existing environments are poorly understood due to the lack of accurate identification of cation bridge formation and stability. In this study, the sorption of sulfamethoxazole (SMX) on montmorillonite (MT) with the coexistence of three different valence metal cations (Na+, Ca2+, and Cr3+) was investigated. Ca2+ and Cr3+ can significantly promote the sorption of SMX on MT for about 5∼10 times promotion, respectively, while Na+ bridges displayed little effect on the sorption of SMX. The sorption binding energy of SMX with MT-Ca (-44.01 kcal/mol) and MT-Cr (-64.57 kcal/mol) bridges was significantly lower than that with MT-Na (-38.45 kcal/mol) and MT (-39.39 kcal/mol), indicating that the sorption affinity of SMX on Cr and Ca bridges was much stronger. The higher valence of the cations also resulted in a more stable adsorbed SMX with less desorption fluctuation. In addition, the relatively higher initial concentration of SMX and the valence of cations increased the bonding density of the cation bridges, thus promoting the apparent sorption of SMX on MT to a certain extent. This work reveals the formation and function of cation bridges in the sorption of SMX on MT. It lays a theoretical foundation for further understanding the environmental fate and risk of organics.

Mediating role of social support in dysphoria, despondency, and quality of life in patients undergoing maintenance hemodialysis.

BACKGROUND: Dysphoria and despondency are prevalent psychological issues in patients undergoing Maintenance Hemodialysis (MHD) that significantly affect their quality of life (QOL). High levels of social support can significantly improve the physical and mental well-being of patients undergoing MHD. Currently, there is limited research on how social support mediates the relationship between dysphoria, despondency, and overall QOL in patients undergoing MHD. It is imperative to investigate this mediating effect to mitigate dysphoria and despondency in patients undergoing MHD, ultimately enhancing their overall QOL. AIM: To investigate the mediating role of social support in relationships between dysphoria, despondency, and QOL among patients undergoing MHD. METHODS: Participants comprised 289 patients undergoing MHD, who were selected using a random sampling approach. The Social Support Rating Scale, Self-Rating Anxiety Scale, Self-Rating Depression Scale, and QOL Scale were administered. Correlation analysis was performed to examine the associations between social support, dysphoria, despondency, and QOL in patients undergoing MHD. To assess the mediating impact of social support on dysphoria, despondency, and QOL in patients undergoing MHD, a bootstrap method was applied. RESULTS: Significant correlations among social support, dysphoria, despondency, and quality in patients undergoing MHD were observed (all P < 0.01). Dysphoria and despondency negatively correlated with social support and QOL (P < 0.01). Dysphoria and despondency had negative predictive impacts on the QOL of patients undergoing MHD (P < 0.05). The direct effect of dysphoria on QOL was statistically significant (P < 0.05). Social support mediated the relationship between dysphoria and QOL, and this mediating effect was significant (P < 0.05). Similarly, the direct effect of despondency on QOL was significant (P < 0.05). Moreover, social support played a mediating role between despondency and QOL, with a significant mediating effect (P < 0.05). CONCLUSION: These findings suggest that social support plays a significant mediating role in the relationship between dysphoria, despondency, and QOL in patients undergoing MHD.