Synthesis of Chiral 1,2-Amino Alcohol-Containing Compounds Utilizing Ruthenium-Catalyzed Asymmetric Transfer Hydrogenation of Unprotected α-Ketoamines.

Herein, we disclose a facile synthetic strategy to access an important class of drug molecules that contain chiral 1,2-amino alcohol functionality utilizing highly effective ruthenium-catalyzed asymmetric transfer hydrogenation of unprotected α-ketoamines. Recently, the COVID-19 pandemic has caused a crisis of shortage of many important drugs, especially norepinephrine and epinephrine, for the treatment of anaphylaxis and hypotension because of the increased demand. Unfortunately, the existing technologies are not fulfilling the worldwide requirement due to the existing lengthy synthetic protocols that require additional protection and deprotection steps. We identified a facile synthetic protocol via a highly enantioselective one-step process for epinephrine and a two-step process for norepinephrine starting from unprotected α-ketoamines 1b and 1a, respectively. This newly developed enantioselective ruthenium-catalyzed asymmetric transfer hydrogenation was extended to the synthesis of many 1,2-amino alcohol-containing drug molecules such as phenylephrine, denopamine, norbudrine, and levisoprenaline, with enantioselectivities of >99% ee and high isolated yields.

Structural Comparisons, Fluorescence Properties, and Glass-to-Crystal Transformations of Heat-Cooled and Melt-Quenched Zeolitic Imidazolate Framework Glass.

As a representative of zeolitic imidazolate framework glass, agZIF-62 has been reported to be synthesized using a melt-quenching method in which the ZIF-62 crystal is heated to a temperature above the melting point. Interestingly, we unexpectedly found that agZIF-62 can also be synthesized by simple heating at temperatures lower than the melting point, which may be assisted by the release of encapsulated solvent molecules. The structural differences between melt-quenched agZIF-62 (MQ-agZIF-62) and heat-cooled agZIF-62 (HC-agZIF-62) were investigated. The results indicated that MQ-agZIF-62 is closer to the liquid state, while HC-agZIF-62 is closer to the crystal state. Interestingly, their luminescent emissions exhibit significant differences. Compared with the ZIF-62 crystal, MQ-agZIF-62 showed a blue-shift of 14 nm, whereas HC-agZIF-62 showed a red-shift of 9 nm. The emission intensity of agZIF-62 is also significantly stronger than that of ZIF-62; thus, rapid semiquantitative detection of the content of the MOF glass in glass and crystal mixtures can be achieved. In addition, HC-agZIF-62 and MQ-agZIF-62 can transform into ZIF-62 crystals via a solvent-media mechanism. This study provides new insights into ZIF-62 glass.

Near-Infrared Blinking Carbon Dots Designed for Quantitative Nanoscopy.

Blinking carbon dots (CDs) have attracted attention as a probe for single molecule localization microscopy (SMLM), yet quantitative analysis is limited because of inept blinking and low signal-to-noise ratio (SNR). Here we report the design and synthesis of near-infrared (NIR) blinking CDs with a maximum emission of around 750 nm by weaving a nitrogen-doped aromatic backbone with surplus carboxyl groups on the surface. The NIR-CDs allow conjugation to monovalent antibody fragments for labeling and imaging of cellular receptors as well as afford increases of 52% in SNR and 33% in localization precision over visible CDs. Analysis of fluorescent bursts allows for accurate counting of cellular receptors at the nanoscale resolution. Using NIR-CDs-based SMLM, we demonstrate oligomerization and internalization of programmed cell death-ligand 1 by a small molecule inhibitor for checkpoint blockade. Our NIR-CDs can become a generally applicable probe for quantitative nanoscopy in chemistry and biology.

Mowing aggravates the adverse effects of nitrogen addition on soil acid neutralizing capacity in a meadow steppe.

Soil acidification induced by reactive nitrogen (N) inputs is a major environmental issue in grasslands, as it lowers the acid neutralizing capacity (ANC). The specific impacts of different N compound forms on ANC remain unclear. Grassland management practices like mowing and grazing can remove a considerable amount of soil N and other nutrients, potentially mitigating soil acidification by removing N from the ecosystem or aggravating it by removing base cations. However, empirical evidence regarding the joint effects of adding different forms of N compounds and mowing on ANC changes in different-sized soil aggregates is still lacking. This study aimed to address this knowledge gap by examining the effects of three N compounds (urea, ammonium nitrate, and ammonium sulfate) combined with mowing (mown vs. unmown) on soil ANC in different soil aggregate sizes (>2000 µm, 250-2000 µm, and <250 µm) through a 6-year field experiment in Inner Mongolia grasslands. We found that the average decline in soil ANC caused by ammonium sulfate (AS) addition (-78.9%) was much greater than that by urea (-25.0%) and ammonium nitrate (AN) (-52.1%) as compared to control. This decline was attributed to increased proton (H+) release from nitrification and the leaching of exchangeable Ca2+ and Mg2+. Mowing aggravated the adverse effects of urea and AN on ANC, primarily due to the reduction in soil organic matter (SOM) contents and the removal of exchangeable Ca2+, K+, and Na + via plant biomass harvest. This pattern was consistent across all aggregate fractions. The lack of variation in soil ANC among different soil aggregate fractions is likely due to the contrasting trend in the distribution of exchangeable Ca2+ and Mg2+. Specifically, the concentration of exchangeable Ca2+ increased with increasing aggregate size, while the opposite was true for that of exchangeable Mg2+. These findings underscore the importance of considering the forms of N compounds when assessing the declines of ANC induced by N inputs, which also calls for an urgent need to reduce N emissions to ensure the sustainable development of the meadow ecosystems.

Deep-Learning-Enhanced Diffusion Imaging Assay for Resolving Local-Density Effects on Membrane Receptors.

G-protein-coupled receptor (GPCR) density at the cell surface is thought to regulate receptor function. Spatially resolved measurements of local-density effects on GPCRs are needed but technically limited by density heterogeneity and mobility of membrane receptors. We now develop a deep-learning (DL)-enhanced diffusion imaging assay that can measure local-density effects on ligand-receptor interactions in the plasma membrane of live cells. In this method, the DL algorithm allows the transformation of 100 ms exposure images to density maps that report receptor numbers over any specified region with ∼95% accuracy by 1 s exposure images as ground truth. With the density maps, a diffusion assay is further established for spatially resolved measurements of receptor diffusion coefficient as well as to express relationships between receptor diffusivity and local density. By this assay, we scrutinize local-density effects on chemokine receptor CXCR4 interactions with various ligands, which reveals that an agonist prefers to act with CXCR4 at low density while an inverse agonist dominates at high density. This work suggests a new insight into density-dependent receptor regulation as well as provides an unprecedented assay that can be applicable to a wide variety of receptors in live cells.

Nonhuman Primate Testing of the Impact of Different Regulatory T Cell Depletion Strategies on Reactivation and Clearance of Latent Simian Immunodeficiency Virus.

Regulatory T cells (Tregs) may be key contributors to the HIV/SIV latent reservoir, since they harbor high levels of HIV/SIV; reverse CD4+ T cell immune activation status, increasing the pool of resting CD4+ T cells; and impair CD8+ T cell function, favoring HIV persistence. We tested the hypothesis that Treg depletion is a valid intervention toward an HIV cure by depleted Tregs in 14 rhesus macaque (RM) controllers infected with SIVsab, the virus that naturally infects sabaeus monkeys, through different strategies: administration of an anti-CCR4 immunotoxin, two doses of an anti-CD25 immunotoxin (interleukin-2 with diphtheria toxin [IL-2-DT]), or two combinations of both. All of these treatments resulted in significant depletion of the circulating Tregs (>70%) and their partial depletion in the gut (25%) and lymph nodes (>50%). The fractions of CD4+ T cells expressing Ki -67 increased up to 80% in experiments containing IL-2-DT and only 30% in anti-CCR4-treated RMs, paralleled by increases in the inflammatory cytokines. In the absence of ART, plasma virus rebounded to 103 vRNA copies/ml by day 10 after IL-2-DT administration. A large but transient boost of the SIV-specific CD8+ T cell responses occurred in IL-2-DT-treated RMs. Such increases were minimal in the RMs receiving anti-CCR4-based regimens. Five RMs received IL-2-DT on ART, but treatment was discontinued because of high toxicity and lymphopenia. As such, while all treatments depleted a significant proportion of Tregs, the side effects in the presence of ART prevent their clinical use and call for different Treg depletion approaches. Thus, based on our data, Treg targeting as a strategy for HIV cure cannot be discarded.IMPORTANCE Regulatory T cells (Tregs) can decisively contribute to the establishment and persistence of the HIV reservoir, since they harbor high levels of HIV/SIV, increase the pool of resting CD4+ T cells by reversing their immune activation status, and impair CD8+ T cell function, favoring HIV persistence. We tested multiple Treg depletion strategies and showed that all of them are at least partially successful in depleting Tregs. As such, Treg depletion appears to be a valid intervention toward an HIV cure, reducing the size of the reservoir, reactivating the virus, and boosting cell-mediated immune responses. Yet, when Treg depletion was attempted in ART-suppressed animals, the treatment had to be discontinued due to high toxicity and lymphopenia. Therefore, while Treg targeting as a strategy for HIV cure cannot be discarded, the methodology for Treg depletion has to be revisited.

The effect of interaction between EtOH dosage and exposure time on gene expression in DPSC.

Alcohol (EtOH) dosage and exposure time can affect gene expression. However, whether there exists synergistic effect is unknown. Here, we analyzed the hDPSC gene microarray dataset GSE57255 downloaded from Gene Expression Omnibus and found that the interaction between EtOH dosage and exposure time on gene expression are statistically significant for two probes: 201917_s_at near gene SLC25A36 and 217649_at near gene ZFAND5. GeneMania showed that SLC25A36 and ZFAND5 were related to 20 genes, three of which had alcohol-related functions. WebGestalt revealed that the 22 genes were enriched in 10 KEGG pathways, four of which are related to alcoholic diseases. We explored the possible nonlinear interaction effect and got 172 gene probes with significant p-values. However, no significantly enriched pathways based on the 172 probes were detected. Our analyses indicated a possible molecular mechanism that could help explain why alcohol consumption has both deleterious and beneficial effects on human health.

Outer membrane vesicles displaying engineered glycotopes elicit protective antibodies.

The O-antigen polysaccharide (O-PS) component of lipopolysaccharides on the surface of gram-negative bacteria is both a virulence factor and a B-cell antigen. Antibodies elicited by O-PS often confer protection against infection; therefore, O-PS glycoconjugate vaccines have proven useful against a number of different pathogenic bacteria. However, conventional methods for natural extraction or chemical synthesis of O-PS are technically demanding, inefficient, and expensive. Here, we describe an alternative methodology for producing glycoconjugate vaccines whereby recombinant O-PS biosynthesis is coordinated with vesiculation in laboratory strains of Escherichia coli to yield glycosylated outer membrane vesicles (glycOMVs) decorated with pathogen-mimetic glycotopes. Using this approach, glycOMVs corresponding to eight different pathogenic bacteria were generated. For example, expression of a 17-kb O-PS gene cluster from the highly virulent Francisella tularensis subsp. tularensis (type A) strain Schu S4 in hypervesiculating E. coli cells yielded glycOMVs that displayed F. tularensis O-PS. Immunization of BALB/c mice with glycOMVs elicited significant titers of O-PS-specific serum IgG antibodies as well as vaginal and bronchoalveolar IgA antibodies. Importantly, glycOMVs significantly prolonged survival upon subsequent challenge with F. tularensis Schu S4 and provided complete protection against challenge with two different F. tularensis subsp. holarctica (type B) live vaccine strains, thereby demonstrating the vaccine potential of glycOMVs. Given the ease with which recombinant glycotopes can be expressed on OMVs, the strategy described here could be readily adapted for developing vaccines against many other bacterial pathogens.

The effects of galectin-3 depletion apheresis on induced skin inflammation in a porcine model.

Galectin-3 (Gal-3), a ß-galactoside-binding lectin that is expressed in mammalian cells, is known to modulate several biological functions such as cell-cell adhesion, macrophage activation, angiogenesis, metastasis, and fibrosis. The goal of this study was to evaluate the ability of Gal-3 depletion apheresis using an adsorption column with immobilized anti-Gal-3-antibody to reduce inflammation induced by Complete Freund's Adjuvant injection in a skin inflammation porcine model. Here, we report that plasma perfusion by apheresis through a Gal-3 binding immuno-affinity column reduces plasma Gal-3 levels to below limits of quantitative detection, and results in significant decrease in skin inflammation, including degree and duration of inflammatory lesions. Human plasma was tested ex vivo and found to be efficiently depleted using the anti-Gal-3 affinity column. This study demonstrates the potential of Gal-3 depletion apheresis as a therapeutic method for inflammation-mediated disease, supporting continued research in this area for clinical application.

Molecular characteristics of ofloxacin mono-resistant Mycobacterium tuberculosis isolates from new and previously treated tuberculosis patients.

BACKGROUND: Ofloxacin (OFX) resistant Mycobacterium tuberculosis (MTB) isolates have been increasingly observed and are a major concern in recent years. This study investigated the genetic mutations associated with OFX resistance among clinical OFX mono-resistant MTB isolates from new and previously treated tuberculosis patients. METHODS: A total of 50 unrelated OFX mono-resistant MTB isolates were analyzed. For all isolates, the quinolone resistance determining regions of gyrA and gyrB were PCR amplified and sequenced. RESULTS: Single mutations in the quinolone resistance determining regions of gyrA (positions D94A, G, N, and Y; A90V; and S91P) and gyrB (positions T539A and E540D) were observed in 62% (31/50) and 4% (2/50) of all OFX mono-resistant isolates, respectively. No differences were detected between the proportions of isolates with mutations in gyrA/gyrB from new and previously treated tuberculosis patients (P=.820). CONCLUSIONS: Although mutations in gyrB were rare, they were as important as mutations in gyrA in predicting OFX resistance in MTB in Tianjin, China.

Methods for the detection and serum depletion of porcine galectin-3.

BACKGROUND: Circulating galectin-3 (Gal-3) is elevated in systemic inflammatory disorders, fibrotic diseases, and in cancers. Gal-3 is a promising cancer target where it promotes tumorigenesis and metastasis, as well as in renal, pulmonary, hepatic, and cardiovascular diseases, because of its role as a driver of fibrotic remodeling. This reports goal was to establish methods for the detection and removal of porcine Gal-3 that will enable further studies of the therapeutic potential of Gal-3 depletion by apheresis in porcine disease models. The long-term aim is to develop a safe, effective method of removing Gal-3 via apheresis as a standalone therapeutic tool and as an adjuvant to other therapies. METHODS: Purified recombinant porcine Gal-3 was prepared and used as the standard for development of a porcine Gal-3 enzyme-linked immunosorbent assay (ELISA). Different affinity column matrices that incorporated either a rat IgG2a anti-Gal-3 monoclonal antibody or carbohydrate ligand were assessed for depletion of Gal-3 from porcine serum. RESULTS: A porcine Gal-3 ELISA with a linear range from 0.3 to 20 ng/mL was able to detect native porcine Gal-3 in both fetal (∼150-200 ng/mL) and juvenile (∼5-15 ng/mL) porcine serum samples. Use of an anti-Gal-3 monoclonal antibody affinity column depleted Gal-3 from porcine serum to at least 313 pg/mL, the limit of ELISA detection. CONCLUSIONS: Methods have been developed for the detection and depletion of porcine Gal-3. These methods will be used to study the specific effects of Gal-3 depletion via apheresis in porcine models of disease.

Hydrogen peroxide suppresses TRPM4 trafficking to the apical membrane in mouse cortical collecting duct principal cells.

A Ca2+-activated nonselective cation channel (NSCCa) is found in principal cells of the mouse cortical collecting duct (CCD). However, the molecular identity of this channel remains unclear. We used mpkCCDc14 cells, a mouse CCD principal cell line, to determine whether NSCCa represents the transient receptor potential (TRP) channel, the melastatin subfamily 4 (TRPM4). A Ca2+-sensitive single-channel current was observed in inside-out patches excised from the apical membrane of mpkCCDc14 cells. Like TRPM4 channels found in other cell types, this channel has an equal permeability for Na+ and K+ and has a linear current-voltage relationship with a slope conductance of ~23 pS. The channel was inhibited by a specific TRPM4 inhibitor, 9-phenanthrol. Moreover, the frequency of observing this channel was dramatically decreased in TRPM4 knockdown mpkCCDc14 cells. Unlike those previously reported in other cell types, the TRPM4 in mpkCCDc14 cells was unable to be activated by hydrogen peroxide (H2O2). Conversely, after treatment with H2O2, TRPM4 density in the apical membrane of mpkCCDc14 cells was significantly decreased. The channel in intact cell-attached patches was activated by ionomycin (a Ca2+ ionophore), but not by ATP (a purinergic P2 receptor agonist). These data suggest that the NSCCa current previously described in CCD principal cells is actually carried through TRPM4 channels. However, the physiological role of this channel in the CCD remains to be further determined.

Versatile Photocrosslinked Protein Hydrogel Matrix for Magnetic-Nanoparticle-Doping and Biomineralization.

A versatile template biomaterial was facilely obtained by ultraviolet (UV) photocrosslinking approach using protein molecules as building blocks. As-formed photocrosslinked protein hydrogel matrix (PPHM) was proved to be composed of covalently bound and dense packing protein molecules. Therefore, the PPHM was endowed with highly smooth topograghy with an average roughness of approximately 5 nm, and was self-supporting and flexible. The PPHM could be easily functionalized by doping Fe3O4 magnetic nanoparticles inside the protein hydrogel. Further, PPHM was experimentally demonstrated to be used as a applicable template for biomineralization.

Measurement Matrix Optimization and Mismatch Problem Compensation for DLSLA 3-D SAR Cross-Track Reconstruction.

With a short linear array configured in the cross-track direction, downward looking sparse linear array three-dimensional synthetic aperture radar (DLSLA 3-D SAR) can obtain the 3-D image of an imaging scene. To improve the cross-track resolution, sparse recovery methods have been investigated in recent years. In the compressive sensing (CS) framework, the reconstruction performance depends on the property of measurement matrix. This paper concerns the technique to optimize the measurement matrix and deal with the mismatch problem of measurement matrix caused by the off-grid scatterers. In the model of cross-track reconstruction, the measurement matrix is mainly affected by the configuration of antenna phase centers (APC), thus, two mutual coherence based criteria are proposed to optimize the configuration of APCs. On the other hand, to compensate the mismatch problem of the measurement matrix, the sparse Bayesian inference based method is introduced into the cross-track reconstruction by jointly estimate the scatterers and the off-grid error. Experiments demonstrate the performance of the proposed APCs' configuration schemes and the proposed cross-track reconstruction method.

Road-Aided Ground Slowly Moving Target 2D Motion Estimation for Single-Channel Synthetic Aperture Radar.

To detect and estimate ground slowly moving targets in airborne single-channel synthetic aperture radar (SAR), a road-aided ground moving target indication (GMTI) algorithm is proposed in this paper. First, the road area is extracted from a focused SAR image based on radar vision. Second, after stationary clutter suppression in the range-Doppler domain, a moving target is detected and located in the image domain via the watershed method. The target's position on the road as well as its radial velocity can be determined according to the target's offset distance and traffic rules. Furthermore, the target's azimuth velocity is estimated based on the road slope obtained via polynomial fitting. Compared with the traditional algorithms, the proposed method can effectively cope with slowly moving targets partly submerged in a stationary clutter spectrum. In addition, the proposed method can be easily extended to a multi-channel system to further improve the performance of clutter suppression and motion estimation. Finally, the results of numerical experiments are provided to demonstrate the effectiveness of the proposed algorithm.

Expression and purification of the recombinant porcine NK-lysin in Pichia pastoris and observation of anticancer activity in vitro.

Natural killer (NK)-lysin, a broad-spectrum antimicrobial peptide, has antitumor and antibactericidal activities against both gram-positive and gram-negative bacteria. In this study the recombinant porcine NK-lysin was expressed and purified in the Pichia pastoris system, and then 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide was used to assess its anticancer activity in vitro. The results showed that the recombinant porcine NK-lysin possesses potent antitumor activity against the human hepatocellular carcinoma cell line SMMC-7721 in a time- and dose-dependent manner, but has negligible hemolysis activity against human erythrocytes. Scanning electronic microscopy was used to directly observe the ultrastructure of SMMC-7721 cells treated with NK-lysin; untreated cells showed lamellipodia and filopodia scattered with the cell surface, with good cell-cell contacts among neighboring cells. In contrast, treated tumor cells exhibited marked alterations in cell morphology, and cell-cell contacts disappeared among neighboring cells. Compared with the untreated tumor cells, the tumor cells treated with NK-lysin for 12 and 24 hr were suppressed for the expression of fascin 1. Thus, the recombinant porcine NK-lysin potentially could be developed as a therapeutic agent for inhibiting tumor growth.

Oleanolic acid derivatives inhibit the Wnt/ß-catenin signaling pathway by promoting the phosphorylation of ß-catenin in human SMMC-7721 cells.

Oleanolic acid, isolated from privet, has shown antitumor effects in several cancers. However, the underlying molecular mechanism associated with these effects is largely unknown. In this study, we explored the effect of oleanolic acid derivatives on the Wnt/ß-catenin signaling pathway in human hepatocellular carcinoma SMMC-7721 cells. The mRNA and protein levels of related genes were determined by real-time quantitative PCR and Western blot, respectively. Treatment of SMMC-7721 cells with oleanolic acid derivatives led to the downregulation of the mRNA and protein levels of ß-catenin, c-myc, and cyclin D1. Treatment with oleanolic acid derivatives decreased the levels of ß-catenin in both the cytoplasm and the nucleus. Moreover, oleanolic acid derivatives promoted the phosphorylation of ß-catenin (Ser33/37/Thr41) in the cytoplasm. Our results suggest that oleanolic acid derivatives inhibit the Wnt/ß-catenin signaling pathway by stimulating the phosphorylation of ß-catenin (Ser33/37/Thr41) in human SMMC-7721 cells.

Unusual galactofuranose modification of a capsule polysaccharide in the pathogenic yeast Cryptococcus neoformans.

Galactofuranose (Galf) is the five-membered ring form of galactose. Although it is absent from mammalian glycans, it occurs as a structural and antigenic component of important cell surface molecules in a variety of microbes, ranging from bacteria to parasites and fungi. One such organism is Cryptococcus neoformans, a pathogenic yeast that causes lethal meningoencephalitis in immunocompromised individuals, particularly AIDS patients. C. neoformans is unique among fungal pathogens in bearing a complex polysaccharide capsule, a critical virulence factor reported to include Galf. Notably, how Galf modification contributes to the structure and function of the cryptococcal capsule is not known. We have determined that Galf is ß1,2-linked to an unusual tetrasubstituted galactopyranose of the glucuronoxylomannogalactan (GXMGal) capsule polysaccharide. This discovery fills a longstanding gap in our understanding of a major polymer of the cryptococcal capsule. We also engineered a C. neoformans strain that lacks UDP-galactopyranose mutase; this enzyme forms UDP-Galf, the nucleotide sugar donor required for Galf addition. Mutase activity was required for the incorporation of Galf into glucuronoxylomannogalactan but was dispensable for vegetative growth, cell integrity, and virulence in a mouse model.

Design of pulse waveform for waveform division multiple access UWB wireless communication system.

A new multiple access scheme, Waveform Division Multiple Access (WDMA) based on the orthogonal wavelet function, is presented. After studying the correlation properties of different categories of single wavelet functions, the one with the best correlation property will be chosen as the foundation for combined waveform. In the communication system, each user is assigned to different combined orthogonal waveform. Demonstrated by simulation, combined waveform is more suitable than single wavelet function to be a communication medium in WDMA system. Due to the excellent orthogonality, the bit error rate (BER) of multiuser with combined waveforms is so close to that of single user in a synchronous system. That is to say, the multiple access interference (MAI) is almost eliminated. Furthermore, even in an asynchronous system without multiuser detection after matched filters, the result is still pretty ideal and satisfactory by using the third combination mode that will be mentioned in the study.

Associations between serum 25-hydroxyvitamin D and prognosis of chronic kidney disease: a prospective cohort study.

BACKGROUND AND OBJECTIVES: 25-hydroxyvitamin D [25(OH)D] deficiency is prevalent in patients with chronic kidney disease (CKD), the associations between serum 25(OH)D levels and mortality in patients with CKD remain unclear, and this study aimed to explore these associations further. METHODS: 4989 participants with CKD were enrolled in the study, and the Cox regression model was used to assess the effects of serum 25(OH)D concentrations on mortality risk. A restricted cubic spline model was used to explore the dose-response relationships, and threshold effect analysis was performed based on inflection points identified by a two-piecewise linear regression model. In addition, subgroup and sensitivity analyses were employed. RESULTS: 1255 participants died during a mean follow-up period of 70 months. Compared with the 25(OH)D-deficient group, the fully adjusted hazard ratios and 95% confidence intervals for the 25(OH)D-adequate group were 0.631 (0.545, 0.730) for all-cause mortality, 0.569 (0.435, 0.743) for cardiovascular mortality, 0.637 (0.461, 0.878) for hypertension mortality, and cancer mortality was 0.596 (0.426, 0.834). The inflection points of serum 25(OH)D concentration affecting all-cause and cardiovascular mortality were 89 nmol/L, and 107 nmol/L, respectively. Subgroup analyses and interaction tests suggested that the effects varied across populations. The results of sensitivity analyses indicated a reliable correlation. CONCLUSION: We found an association between serum 25(OH)D concentrations and the prognosis of patients with CKD as a reliable predictor of early intervention and intensive care.