Fluorinated chlorin chromophores for red-light-driven CO2 reduction.

The utilization of low-energy photons in light-driven reactions is an effective strategy for improving the efficiency of solar energy conversion. In nature, photosynthetic organisms use chlorophylls to harvest the red portion of sunlight, which ultimately drives the reduction of CO2. However, a molecular system that mimics such function is extremely rare in non-noble-metal catalysis. Here we report a series of synthetic fluorinated chlorins as biomimetic chromophores for CO2 reduction, which catalytically produces CO under both 630 nm and 730 nm light irradiation, with turnover numbers of 1790 and 510, respectively. Under appropriate conditions, the system lasts over 240 h and stays active under 1% concentration of CO2. Mechanistic studies reveal that chlorin and chlorinphlorin are two key intermediates in red-light-driven CO2 reduction, while corresponding porphyrin and bacteriochlorin are much less active forms of chromophores.

Pyridinethiolate-Capped CdSe Quantum Dots for Red-Light-Driven H2 Production in Water.

The utilization of low-energy sunlight to produce renewable fuels is a subject of great interest. Here we report the first example of metal chalcogenide quantum dots (QDs) capped with a pyridinethiolate carboxylic acid (pyS-COOH) for red-light-driven H2 production in water. The precious-metal-free system is robust over 240 h, and achieves a turnover number (TON) of 43910 ± 305 (vs Ni) with a rate of 31570 ± 1690 mmol g-1 h-1 for hydrogen production. In contrast to the inactive QDs capped with other thiolate ligands, the CdSe-pyS-COOH QDs give a significantly higher singlet oxygen quantum yield [ΦΔ (1O2)] in solution.

Comparison of 68Ga-FAPI-04 and 18F-FDG PET/CT in diagnosing ovarian cancer.

PURPOSE: This study assesses the diagnostic performance of 68Ga-FAPI-04 PET/CT compared to 18F-FDG PET/CT in primary, recurrent, and metastatic ovarian cancer. METHODS: Seventy-nine ovarian cancer patients who performed 68Ga-FAPI-04 and 18F-FDG PET/CT were recruited. The target-to-background ratio (TBR), maximum standardized uptake value (SUVmax), the number of positive lesions, visual assessment, the peritoneal cancer index (PCI) score, staging/restaging, and treatment strategies were compared from the corresponding PET/CT. Additionally, we analyzed and contrasted the diagnostic efficacy in both scans. RESULTS: Among all patients, 6 were assessed for initial assessment and 73 for recurrence and metastasis detection. For all lesions, 68Ga-FAPI-04 PET/CT demonstrated greater TBR than 18F-FDG PET/CT. 68Ga-FAPI-04 PET/CT demonstrated higher sensitivity for peritoneal metastases including patient-based and lesion-based analysis (95.00% vs. 83.33%, P = 0.065; 90.16% vs. 60.66%, P < 0.001) and a higher PCI score [median PCI: 6 (4, 12) vs. 4 (2, 8), P < 0.001]. According to the visual assessment, 68Ga-FAPI-04 PET revealed larger extent metastases in 55.93% (33/59) of the patients with peritoneal metastases. 68Ga-FAPI-04 was upstaged in 7 patients (8.86%, 7/79) and discrepancies in both scans caused treatment strategies to change in 11 patients (13.92%, 11/79). CONCLUSION: 68Ga-FAPI-04 PET/CT outperforms 18F-FDG PET/CT in identifying metastases and can be a potential supplement for managing ovarian cancer patients.

Photocatalytic CO2 reduction with iron porphyrin catalysts and anthraquinone dyes.

Herein we studied visible-light-driven CO2 reduction using a series of tetra-phenylporphyrin iron catalysts and inexpensive anthraquinone dyes. Varying the functional groups on the phenyl moieties of the catalysts significantly enhances the photocatalytic activity, achieving an optimal turnover number (TON) of 10 476 and a selectivity of 100% in the noble-metal-free systems. The highest activity found in a bromo-substituted catalyst is attributed to favorable electron transfer from the photosensitizer to the iron porphyrin.

Targeting GDP-Dissociation Inhibitor Beta (GDI2) with a Benzo[a]quinolizidine Library to Induce Paraptosis for Cancer Therapy.

Inducing paraptosis, a nonapoptotic form of cell death, has great therapeutic potential in cancer therapy, especially for drug-resistant tumors. However, the specific molecular target(s) that trigger paraptosis have not yet been deciphered yet. Herein, by using activity-based protein profiling, we identified the GDP-dissociation inhibitor beta (GDI2) as a manipulable target for inducing paraptosis and uncovered benzo[a]quinolizidine BQZ-485 as a potent inhibitor of GDI2 through the interaction with Tyr245. Comprehensive target validation revealed that BQZ-485 disrupts the intrinsic GDI2-Rab1A interaction, thereby abolishing vesicular transport from the endoplasmic reticulum (ER) to the Golgi apparatus and initiating subsequent paraptosis events including ER dilation and fusion, ER stress, the unfolded protein response, and cytoplasmic vacuolization. Based on the structure of BQZ-485, we created a small benzo[a]quinolizidine library by click chemistry and discovered more potent GDI2 inhibitors using a NanoLuc-based screening platform. Leveraging the engagement of BQZ-485 with GDI2, we developed a selective GDI2 degrader. The optimized inhibitor (+)-37 and degrader 21 described in this study exhibited excellent in vivo antitumor activity in two GDI2-overexpressing pancreatic xenograft models, including an AsPc-1 solid tumor model and a transplanted human PDAC tumor model. Altogether, our findings provide a promising strategy for targeting GDI2 for paraptosis in the treatment of pancreatic cancers, and these lead compounds could be further optimized to be effective chemotherapeutics.

Structural insights into FSP1 catalysis and ferroptosis inhibition.

Ferroptosis suppressor protein 1 (FSP1, also known as AIMF2, AMID or PRG3) is a recently identified glutathione-independent ferroptosis suppressor1-3, but its underlying structural mechanism remains unknown. Here we report the crystal structures of Gallus gallus FSP1 in its substrate-free and ubiquinone-bound forms. The structures reveal a FAD-binding domain and a NAD(P)H-binding domain, both of which are shared with AIF and NADH oxidoreductases4-9, and a characteristic carboxy-terminal domain as well. We demonstrate that the carboxy-terminal domain is crucial for the catalytic activity and ferroptosis inhibition of FSP1 by mediating the functional dimerization of FSP1, and the formation of two active sites located on two sides of FAD, which are responsible for ubiquinone reduction and a unique FAD hydroxylation respectively. We also identify that FSP1 can catalyze the production of H2O2 and the conversion of FAD to 6-hydroxy-FAD in the presence of oxygen and NAD(P)H in vitro, and 6-hydroxy-FAD directly inhibits ferroptosis in cells. Together, these findings further our understanding on the catalytic and ferroptosis suppression mechanisms of FSP1 and establish 6-hydroxy-FAD as an active cofactor in FSP1 and a potent radical-trapping antioxidant in ferroptosis inhibition.

Long-term groundwater geochemical evolution induced by coal mining activities-a case study of floor confined limestone aquifer in Yaoqiao Coal Mine, Jiangsu, China.

Groundwater chemical composition can be changed due to long-term coal mining activities, but it was unclear how it was induced in Taiyuan Formation limestone (TFL) regarding the lack of relevant quantitative studies. The aim of this research is to improve understanding of the chemical composition changes in groundwater of L4 limestone in the coal mining area based on the available hydrochemical and hydrodynamical reports and studies during the period 1978-2020. The systematical analysis of the groundwater composition and field allows to make the hydrogeological characterization with the relatively independent blocks by the factor groups "Planar division & Vertical zonation" and "High water pressure, Poor recharge & Little water inflow," which determines different hydrochemical types and high TDS concentration. The long-term groundwater drainage has caused the eastern and southern limestone aquifer to demonstrate a wide range of depression cones and depletion of groundwater resources, the majority areas were dewatered, and the karstification process changed significantly. An analysis of chemical compositions changes due to extensive permanent drainage of L4 limestone water revealed the decrease in the TDS concentration. The solubility of calcite, dolomite, and gypsum changed, which resulted in the decreasing tendency of Ca2+ + Mg2+ ions. Evaporation and concentration were found to be the main factors determining the L4 limestone water composition, whereas ion exchange was the primary factor for rock-water interaction. These findings are helpful for mine enterprises to take necessary measures for preventing and controlling the groundwater quality degradation from the extensive coalmine drainage.

Steroid-resistant nephrotic syndrome associated with certain SGPL1 variants in a family: Case report and literature review.

Objectives: Steroid-resistant nephrotic syndrome (SRNS) is a clinical syndrome characterized by the lack of response to standard steroid therapy, usually progressing to end-stage renal disease. We reported two cases of female identical twins with SRNS caused by SGPL1 variants in one family, reviewed the relevant literature, and summarized their clinical phenotypes, pathological types, and genotypic characteristics. Methods: Two cases of nephrotic syndrome caused by SGPL1 variants were admitted to Tongji Hospital, affiliated with Tongji Medical College of Huazhong University of Science and Technology. Their clinical data were retrospectively collected, and the peripheral blood genomic DNA was captured and sequenced by whole exome sequencing. Related literature published in PubMed, CNKI, and Wan fang databases was reviewed. Results: We described two Chinese identical twin girls with isolated SRNS due to compound heterozygous variants in the SGPL1 (intron4 c.261 + 1G > A and intron12 c.1298 + 6T > C). The patients were followed up for 60.0 months and 53.0 months, respectively, having no extra-renal manifestations. They all died due to renal failure. A total of 31 children with SGPL1 variants causing nephrotic syndrome (including the reported two cases) were identified through a literature review. Conclusions: These two female identical twins were the first reported cases of isolated SRNS caused by SGPL1 variants. Almost all homozygous and compound heterozygous variants of SGPL1 had extra-renal manifestations, but compound heterozygous variants in the intron of SGPL1 may have no obvious extra-renal manifestations. Additionally, a negative genetic testing result does not completely rule out genetic SRNS because the Human Gene Mutation Database or ClinVar is constantly being updated.

Photocatalytic CO2 reduction with aminoanthraquinone organic dyes.

The direct utilization of solar energy to convert CO2 into renewable chemicals remains a challenge. One essential difficulty is the development of efficient and inexpensive light-absorbers. Here we show a series of aminoanthraquinone organic dyes to promote the efficiency for visible light-driven CO2 reduction to CO when coupled with an Fe porphyrin catalyst. Importantly, high turnover numbers can be obtained for both the photosensitizer and the catalyst, which has not been achieved in current light-driven systems. Structure-function study performed with substituents having distinct electronic effects reveals that the built-in donor-acceptor property of the photosensitizer significantly promotes the photocatalytic activity. We anticipate this study gives insight into the continued development of advanced photocatalysts for solar energy conversion.

Molecular Nickel Thiolate Complexes for Electrochemical Reduction of CO2 to C1-3 Hydrocarbons.

We report the unprecedented electrocatalytic activity of a series of molecular nickel thiolate complexes (1-5) in reducing CO2 to C1-3 hydrocarbons on carbon paper in pH-neutral aqueous solutions. Ni(mpo)2 (3, mpo=2-mercaptopyridyl-N-oxide), Ni(pyS)3 - (4, pyS=2-mercaptopyridine), and Ni(mp)2 - (5, mp=2-mercaptophenolate) were found to generate C3 products from CO2 for the first time in molecular complex. Compound 5 exhibits Faradaic efficiencies (FEs) of 10.6 %, 7.2 %, 8.2 % for C1 , C2 , C3 hydrocarbons respectively at -1.0 V versus the reversible hydrogen electrode. Addition of CO to the system significantly promotes the FEC1-C3 to 41.1 %, suggesting that a key Ni-CO intermediate is associated with catalysis. A variety of spectroscopies have been performed to show that the structures of nickel complexes remain intact during CO2 reduction.

Epidemiological characteristics and risk factors of obstetric infection after the Universal Two-Child Policy in North China: a 5-year retrospective study based on 268,311 cases.

BACKGROUND: Obstetrical infection is one of the causes of maternal death and a difficult problem for many clinicians. Changes in the demographic and obstetric background of pregnant women following the Universal Two-Child Policy may have an impact on some fertility phenomena. And with the increase in the number of deliveries, the limited medical resources become more scarce. How will China's health system quickly adapt to the growing needs and expectations for maternal health and ensure the provision of qualified and accessible medical services? In addition, what social support measures should be provided to reduce preventable obstetric complications? Given the relatively low per capita share of medical resources in China, how should China deal with the impact of the Universal Two-Child Policy? Therefore, more studies based on the change of fertility policy are needed. We try to analyze the epidemiological characteristics and risk factors of obstetric infection before and after the Universal Two-Child Policy, with a view to providing reference for the prevention and control of obstetric infection in regions after the change of fertility policy, and also hope to make corresponding contributions to the solution of the above problems through relevant studies. METHODS: The subjects of the survey were 268,311 pregnant women from Hebei Province Maternal Near Miss Surveillance System (HBMNMSS) of Hebei Women and Children's Health Center from January 1, 2013 to December 31, 2017. We analyzed the region, time and population distribution characteristics of obstetric infection, compared the epidemiological factors of obstetric infection before and after the Universal Two-Child Policy, and analyzed the relevant risk factors of obstetric infection. RESULTS: The incidence of obstetric infection increased nearly twice after the Universal Two-Child Policy. The incidence of obstetric infection was highest in Chengde (1.9%), a city with a northward geographical distribution, Baoding (1.6%), Cangzhou (1.5%) followed; The higher the hospital grade, the higher the incidence; The incidence of obstetric infections in hospitals at all levels has increased; The age of onset before the Universal Two-Child Policy was (27.82 ± 5.047) years old, and the age after the Universal Two-Child Policy was (28.97 ± 4.880) years old; The incidence of obstetric infections is higher in winter. The rate of abortion-related infection (increased from 0.61 to 1.65%) and the rate of pregnant women with high school education (increased from 0.35 to 0.74%) increased significantly. The results of multivariate Logistic regression analysis after the Universal Two-Child Policy showed that anemia (OR = 1.249, 95%CI: 1.071-1.458), chronic hypertension (OR = 1.934, 95%CI: 1.375-2.722), mild preeclampsia (OR = 2.103, 95%CI: 1.323-3.344) and severe preeclampsia (OR = 2.228, 95%CI: 1.703-2.916) were independent risk factors for obstetric infection. Gestational age ≥ 37 weeks was a protective factor. CONCLUSION: After the Universal Two-Child Policy, the prevention and control of obstetric infections should be strengthened, especially for abortion-related infections and elderly maternal with obstetric complications and complication in high-grade hospitals in winter. Educational background is also one of the factors that should be considered in the prevention of obstetric sensation. Prolonging gestational age is helpful to reduce the incidence of obstetric infection.

Efficient Red-Light-Driven Hydrogen Evolution with an Anthraquinone Organic Dye.

The direct utilization of the full solar spectrum to obtain renewable fuels remains a challenge because the conversion of the low-energy light (red and near-infrared) is difficult. Current light-driven systems show activity for hydrogen generation with the high-energy part of sunlight. Here we report the use of a simple anthraquinone organic dye in an artificial photosynthetic system that promotes efficient red-light-driven production of hydrogen. The system contains no noble metal and exhibits a turnover number greater than 0.78 million and a quantum yield of 30.6% at 630 nm. A mechanistic study revealed that the excited-state and redox properties of the chromophore are critical to achieving high activity and stability.

Improving Photocatalytic Hydrogen Production through Incorporating Copper to Organic Photosensitizers.

Organic dyes have been investigated extensively as promising photosensitizers in noble-metal-free photocatalytic systems for hydrogen production. However, other than functional group optimization, there are very few methods reported to be effective in improving their photocatalytic activity. Herein, we report the incorporation of Cu2+ into purpurin and gallein dyes for visible-light-driven hydrogen production. These Cu-dye chromophores significantly promote the photocatalytic activity of homogeneous systems when paired with a series of molecular Ni or Fe catalysts. Under optimal conditions, the Cu-purpurin and Cu-gallein photosensitizers exhibit more than 20-fold increases in turnover frequencies for hydrogen evolution when compared with purpurin and gallein. Catalytic systems with the Cu-purpurin chromophore show no decrease in activity over 120 h. Based on electrochemical and fluorescence quenching experiments, the enhancement of photocatalytic activity is likely due to the fact that Cu2+ can facilitate the transfer of electrons from the photosensitizers to the catalysts through creating highly reducing centers.

Selective CO2 Reduction to Ethylene Using Imidazolium-Functionalized Copper.

Electrochemical CO2 reduction is a promising approach to obtain sustainable chemicals in energy conversion. Improving the selectivity of CO2 reduction toward a particular C2 product such as ethylene remains a significant challenge. Herein, we report a series of imidazolium hexafluorophosphate compounds as surface modifiers for planar Cu foils to boost the Faradaic efficiency (FE) of ethylene from 5 to 73%, which is among the highest reported using polycrystalline Cu. The modified electrodes are convenient to prepare. The structure-function study demonstrates that varying the alkyl or aromatic substituents on the imidazolium nitrogen atoms has significant effects on the morphology of the deposited films and the product selectivity of CO2 reduction. Experimental FEC≥2, FEC2H4, ln(FEC≥2/FECH4), and ln(FEC2H4/FEC2H5OH) values show generally linear relationships with FEH2 while using different imidazolium modifiers, suggesting that factors governing proton reduction may also be directly related to both overall C≥2 generation and ethylene selectivity. This work presents an effective and practical way in tailoring the active sites of metallic surface for selective CO2 reduction.

Co-delivery of Docetaxel and Resveratrol by liposomes synergistically boosts antitumor efficiency against prostate cancer.

Combination therapy is frequently used in cancer treatments. Delivery of combined anticancer agents loaded in a nanocarrier would be a promising option for combination therapy. Here, we designed PEGylated nano-liposomes for co-delivery Docetaxel (Doc) and Resveratrol (Res) to evaluate antitumor efficiency of the combined drugs in prostate cancer. The average diameter of the liposomes was 99.67 nm with a spheral-like shape. Drug release studies showed that both drugs could synchronously leak from the liposomes in a sustained release behavior. Cellular uptake results demonstrated that liposomes could effectively deliver more cargos into cells than other formulations. Moreover, co-loaded liposomes with Doc/Res in a molar ratio of 1:2 exhibited significantly higher cytotoxicity than a mixed solution containing both drugs on cancer cells. In the study of caspase 3, we found that the combination of Doc and Res could significantly increase the activity of caspase 3 enzyme compared with Doc alone. Animal studies revealed that co-encapsulated Doc/Res in liposomes predominantly inhibited tumor growth in PC3 bearing Balb/c nude mice, as evidenced by a change in cell proliferation and apoptosis parameters. Importantly, little toxicities and prolonged survival time were observed in mice treated with liposome-loaded Doc/Res than control group exposed to liposome-free Doc/Res. These results provided evidence that loading of Doc/Res in a nano-liposome is an efficient delivery formulation for synergistic treating prostate cancer.

Clinical and Renal Histology Findings and Different Responses to Induction Treatment Affecting the Long-Term Renal Outcomes of Children With ANCA-Associated Vasculitis: a Single-Center Cohort Analysis.

Introduction: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is relatively rare in children. This article aimed to analyze clinical and renal histology findings and different responses to induction treatment associated with the long-term renal outcomes in children with AAV in a single center. Methods: All pediatric patients with AAV admitted to Tongji Hospital from January 2002 to January 2021 were included in the study. The demographic, clinical, pathological, laboratory, and treatment data and outcomes were collected and analyzed to identify predictors associated with response to induction treatment and progression to end-stage renal disease (ESRD). Results: In total, 48 children with AAV were included in this cohort; 81.25% of them were women, and 91.7% were microscopic polyangiitis (MPA). Kidney involvement was found in 45 patients (93.75%). The most common histopathological subtype was crescentic form in this cohort according to Berden's classification. In total, 34 patients (70.8%) showed eGFR <60 ml/min/1.73 m2 at the time of diagnosis. Complete and partial remission was achieved in 8 patients (16.7%) and 19 patients (39.6%), respectively, following 6-month induction treatment. Half of the patients eventually progressed to ESRD at a mean time of (13.04 ± 15.83) months after diagnosis. The independent predictors of nonremission following induction treatment and progression to ESRD were baseline eGFR <60 ml/min/1.73 m2 and hypertension at diagnosis. Renal survival significantly decreased over time in patients with renal sclerotic subtypes or those with nonremission following induction treatment by Kaplan-Meier curve estimation. Conclusions: Our study demonstrates that women, MPA, and crescentic subtypes are predominant in pediatric AAV in China. Initial renal failure (eGFR <60 ml/min/1.73 m2), hypertension, sclerotic pathological subtype, and nonremission following induction treatment are predictive of long-term renal outcomes.

AGR2-induced cholesterol synthesis drives lovastatin resistance that is overcome by combination therapy with allicin.

Anterior gradient 2 (AGR2), a protein disulfide isomerase (PDI), is a multifunctional protein under physiological and pathological conditions. In this study we investigated the roles of AGR2 in regulating cholesterol biogenesis, lipid-lowering efficiency of lovastatin as well as in protection against hypercholesterolemia/statin-induced liver injury. We showed that AGR2 knockout significantly decreased hepatic and serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in mice with whole-body or hepatocyte-specific Agr2-null mutant, compared with the levels in their wild-type littermates fed a normal chow diet (NCD) or high-fat diet (HFD). In contrast, mice with AGR2 overexpression (Agr2/Tg) exhibited an increased cholesterol level. Mechanistic studies revealed that AGR2 affected cholesterol biogenesis via activation of AKT/sterol regulatory element-binding protein-2 (SREBP2), to some extent, in a PDI motif-dependent manner. Moreover, elevated AGR2 led to a significant decrease in the lipid-lowering efficacy of lovastatin (10 mg· kg-1· d-1, ip, for 2 weeks) in mice with hypercholesterolemia (hyperCho), which was validated by results obtained from clinical samples in statin-treated patients. We showed that lovastatin had limited effect on AGR2 expression, but AGR2 was inducible in Agr2/Tg mice fed a HFD. Further investigations demonstrated that drug-induced liver toxicity and inflammatory reactions were alleviated in hypercholesterolemic Agr2/Tg mice, suggesting the dual functions of AGR2 in lipid management and hyperCho/statin-induced liver injury. Importantly, the AGR2-reduced lipid-lowering efficacy of lovastatin was attenuated, at least partially, by co-administration of a sulfhydryl-reactive compound allicin (20 mg· kg-1· d-1, ip, for 2 weeks). These results demonstrate a novel role of AGR2 in cholesterol metabolism, drug resistance and liver protection, suggesting AGR2 as a potential predictor for selection of lipid-lowering drugs in clinic.

Combination of Organic Dye and Iron for CO2 Reduction with Pentanuclear Fe2Na3 Purpurin Photocatalysts.

Molecular photocatalysts designed with earth-abundant elements are rare and challenging in artificial photosynthesis study. Herein, we report a multimetallic Fe2Na3 purpurin (1) complex for the reduction of CO2 in DMF under visible-light irradiation. The photocatalytic system achieves 91% selectivity and 2625 ± 334 turnovers of CO in 120 h, which is among the highest reported for a noble-metal-free catalyst without an additional photosensitizer. UV-vis and electrochemical studies suggest that the mechanism involves subsequent reductions and protonations of 1 to generate [FeII2Na3((H)2PP)6]5- and [FeIII2Na3((H)2PP)6]3- as the active photocatalysts in CO2 reduction.

Increased serum cystatin C levels and responses of pancreatic α- and ß-cells in type 2 diabetes.

Background: Increased serum cystatin C (CysC) can predict the onset of type 2 diabetes (T2D). Meanwhile, impaired pancreatic α- and ß-cell functions get involved in the pathophysiological processes of T2D. So this study was to explore the relationships between serum CysC levels and pancreatic α- and ß-cell functions in T2D. Methods: In this cross-sectional observational study, a total of 2634 patients with T2D were consecutively recruited. Each recruited patient received a serum CysC test and oral glucose tolerance test for synchronous detection of serum C-peptide and plasma glucagon. As components of pancreatic ß-cell function, insulin secretion and sensitivity indices were evaluated by C-peptide area under the curve (AUC-CP) and C-peptide-substituted Matsuda's index (Matsuda-CP), respectively. Fasting glucagon (F-GLA) and post-challenge glucagon calculated by glucagon area under the curve (AUC-GLA) were used to assess pancreatic α-cell function. These skewed indices and were further natural log-transformed (ln). Results: With quartiles of serum CysC levels ascending, AUC-CP, F-GLA and AUC-GLA were increased, while Matsuda-CP was decreased (P for trend <0.001). Moreover, serum CysC levels were positively related to lnAUC-CP, lnF-GLA and lnAUC-GLA (r= 0.241, 0.131 and 0.208, respectively, P < 0.001), and inversely related to lnMatsuda-CP (r= -0.195, P < 0.001). Furthermore, after controlling for other relevant variables via multivariable linear regression analysis, serum CysC levels were identified to account for lnAUC-CP (ß= 0.178, t= 10.518, P < 0.001), lnMatsuda-CP (ß= -0.137, t= -7.118, P < 0.001), lnF-GLA (ß= 0.049, t= 2.263, P = 0.024) and lnAUC-GLA (ß= 0.121, t= 5.730, P < 0.001). Conclusions: Increased serum CysC levels may be partly responsible for increased insulin secretion from ß-cells, decreased systemic insulin sensitivity, and elevated fasting and postprandial glucagon secretion from α-cells in T2D.