Loss of mitogen-activated protein kinase phosphate-5 aggravates islet dysfunction in mice with type 1 and type 2 diabetes.

Impaired functionality and loss of islet ß-cells are the primary abnormalities underlying the pathogenesis of both type 1 and 2 diabetes (T1DM and T2DM). However, specific therapeutic and preventive mechanisms underlying these conditions remain unclear. Mitogen-activated protein kinase phosphatase-5 (MKP-5) has been implicated in carcinogenesis, lipid metabolism regulation, and immune cell activation. In a previous study, we demonstrated the involvement of exogenous MKP-5 in the regulation of obesity-induced T2DM. However, the role of endogenous MKP-5 in the T1DM and T2DM processes is unclear. Thus, mice with MKP-5 knockout (KO) were generated and used to establish mouse models of both T1DM and T2DM. Our results showed that MKP-5 KO exacerbated diabetes-related symptoms in mice with both T1DM and T2DM. Given that most phenotypic studies on islet dysfunction have focused on mice with T2DM rather than T1DM, we specifically aimed to investigate the role of endoplasmic reticulum stress (ERS) and autophagy in T2DM KO islets. To accomplish this, we performed RNA sequence analysis to gain comprehensive insight into the molecular mechanisms associated with ERS and autophagy in T2DM KO islets. The results showed that the islets from mice with MKP-5 KO triggered 5' adenosine monophosphate-activated protein kinase (AMPK)-mediated autophagy inhibition and glucose-regulated protein 78 (GRP-78)-dominated ERS. Hence, we concluded that the autophagy impairment, resulting in islet dysfunction in mice with MKP-5 KO, is mediated through GRP-78 involvement. These findings provide valuable insights into the molecular pathogenesis of diabetes and highlight the significant role of MKP-5. Moreover, this knowledge holds promise for novel therapeutic strategies targeting MKP-5 for diabetes management.

Synthesis of 1,2,4-diazaphospholes via base-promoted cyclization reaction of hydrazonoyl chlorides and [Bu4N][P(SiCl3)2].

Aromatic 1,2,4-diazaphospholes featuring distinct hybrid-mode nitrogen atoms (N(λ3σ2), N(λ3σ3)) and low-valent phosphorus atoms (λ3σ2) exhibited the characteristic of serving as unique hybrid ligands. This study presented a one-pot reaction involving the base-promoted stepwise cyclization of hydrazonoyl chlorides and [Bu4N][P(SiCl3)2] to yield 1,2,4-diazaphospholes, providing an effective method for synthesizing such compounds.

Metabolic engineering and mechanical investigation of enhanced plant autoluminescence.

The fungal bioluminescence pathway (FBP) was identified from glowing fungi, which releases self-sustained visible green luminescence. However, weak bioluminescence limits the potential application of the bioluminescence system. Here, we screened and characterized a C3'H1 (4-coumaroyl shikimate/quinate 3'-hydroxylase) gene from Brassica napus, which efficiently converts p-coumaroyl shikimate to caffeic acid and hispidin. Simultaneous expression of BnC3'H1 and NPGA (null-pigment mutant in A. nidulans) produces more caffeic acid and hispidin as the natural precursor of luciferin and significantly intensifies the original fungal bioluminescence pathway (oFBP). Thus, we successfully created enhanced FBP (eFBP) plants emitting 3 × 1011 photons/min/cm2 , sufficient to illuminate its surroundings and visualize words clearly in the dark. The glowing plants provide sustainable and bio-renewable illumination for the naked eyes, and manifest distinct responses to diverse environmental conditions via caffeic acid biosynthesis pathway. Importantly, we revealed that the biosynthesis of caffeic acid and hispidin in eFBP plants derived from the sugar pathway, and the inhibitors of the energy production system significantly reduced the luminescence signal rapidly from eFBP plants, suggesting that the FBP system coupled with the luciferin metabolic flux functions in an energy-driven way. These findings lay the groundwork for genetically creating stronger eFBP plants and developing more powerful biological tools with the FBP system.

Hypoxic preconditioned MSCs-derived small extracellular vesicles for photoreceptor protection in retinal degeneration.

Photoreceptor apoptosis is an important pathogenesis of retinal degeneration and a primary cause of vision loss with limited treatment methods. Mesenchymal stem/stromal cells-derived small extracellular vesicles (MSC-sEVs) have shown therapeutic value in various ocular disorders. Recent studies have revealed that hypoxic preconditioning can improve the effectiveness of MSC-sEVs in tissue regeneration. However, whether hypoxic preconditioned MSC-sEVs (Hyp-sEVs) exert superior effects on photoreceptor protection relative to normoxic conditioned MSC-sEVs (Nor-sEVs) remains unclear. Here, we reported that Hyp-sEVs further improved retinal structure, recovered retinal function, and suppressed photoreceptor apoptosis in N-methyl-N-nitrosourea (MNU)-induced mouse model compared with Nor-sEVs. Hyp-sEVs also exhibited enhanced anti-apoptotic roles in MNU-provoked 661 W cell injury in vitro. We then analyzed the protein profiles of Nor-sEVs and Hyp-sEVs by LC-MS/MS and found that growth-associated protein 43 (GAP43) was enriched in Hyp-sEVs. The knockdown of GAP43 abolished the retinal therapeutic effects of Hyp-sEVs. Mechanistically, hypoxic stimulation-induced hypoxia-inducible factor-1α (HIF-1α) activation was responsible for preventing tripartite motif-containing protein 25 (TRIM25)-mediated GAP43 ubiquitination and degradation, leading to the upregulation of GAP43 in Hyp-sEVs. Together, our findings uncover the efficacy and mechanism of Hyp-sEVs-based photoreceptor protection and highlight the potential of Hyp-sEVs as optimized therapeutics for retinal degeneration.

Detecting Pest-Infested Forest Damage through Multispectral Satellite Imagery and Improved UNet+.

Plant pests are the primary biological threats to agricultural and forestry production as well as forest ecosystem. Monitoring forest-pest damage via satellite images is crucial for the development of prevention and control strategies. Previous studies utilizing deep learning to monitor pest-infested damage in satellite imagery adopted RGB images, while multispectral imagery and vegetation indices were not used. Multispectral images and vegetation indices contain a wealth of useful information for detecting plant health, which can improve the precision of pest damage detection. The aim of the study is to further improve forest-pest infestation area segmentation by combining multispectral, vegetation indices and RGB information into deep learning. We also propose a new image segmentation method based on UNet++ with attention mechanism module for detecting forest damage induced by bark beetle and aspen leaf miner in Sentinel-2 images. The ResNeSt101 is used as the feature extraction backbone, and the attention mechanism scSE module is introduced in the decoding phase for improving the image segmentation results. We used Sentinel-2 imagery to produce a dataset based on forest health damage data gathered by the Ministry of Forests, Lands, Natural Resource Operations and Rural Development (FLNRORD) in British Columbia (BC), Canada, during aerial overview surveys (AOS) in 2020. The dataset contains the 11 original Sentinel-2 bands and 13 vegetation indices. The experimental results confirmed that the significance of vegetation indices and multispectral data in enhancing the segmentation effect. The results demonstrated that the proposed method exhibits better segmentation quality and more accurate quantitative indices with overall accuracy of 85.11%, in comparison with the state-of-the-art pest area segmentation methods.

Evaluation of the Gastric Microbiome in Patients with Chronic Superficial Gastritis and Intestinal Metaplasia.

Objective To evaluate the gastric microbiome in patients with chronic superficial gastritis (CSG) and intestinal metaplasia (IM) and investigate the influence of Helicobacter pylori (H. pylori) on the gastric microbiome. Methods Gastric mucosa tissue samples were collected from 54 patients with CSG and IM, and the patients were classified into the following four groups based on the state of H. pylori infection and histology: H. pylori-negative CSG (n=24), H. pylori-positive CSG (n=14), H. pylori-negative IM (n=11), and H. pylori-positive IM (n=5). The gastric microbiome was analyzed by 16S rRNA gene sequencing. Results H. pylori strongly influenced the bacterial abundance and diversity regardless of CSG and IM. In H. pylori-positive subjects, the bacterial abundance and diversity were significantly lower than in H. pylori-negative subjects. The H. pylori-negative groups had similar bacterial composition and bacterial abundance. The H. pylori-positive groups also had similar bacterial composition but different bacterial relative abundance. The relative abundance of Neisseria, Streptococcus, Rothia, and Veillonella were richer in the I-HP group than in G-HP group, especially Neisseria (t=175.1, P<0.001). Conclusions The gastric microbial abundance and diversity are lower in H. pylori- infected patients regardless of CSG and IM. Compared to H. pylori-positive CSG group and H. pylori-positive IM, the relative abundance of Neisseria, Streptococcus, Rothia, and Veillonella is higher in H. pylori-positive patients with IM than in H. pylori-positive patients with CSG, especially Neisseria.

CuO@CoFe Layered Double Hydroxide Core-Shell Heterostructure as an Efficient Water Oxidation Electrocatalyst under Mild Alkaline Conditions.

Designing hierarchical electrocatalysts with superior water oxidation performance is highly desirable for the production of renewable chemical fuels. Here, we report the development of a CuO@CoFe layered double hydroxide core-shell heterostructure supported on Cu foil (CuO@CoFe-LDH/CF) as a highly active catalyst electrode for water oxidation under mild alkaline conditions. In a 0.2 M carbonate buffer solution (pH 11), it only needs a small overpotential of 213 mV to achieve 10 mA cm-2, outperforming all reported electrocatalysts at comparable testing conditions. It also shows outstanding long-term durability.

Smartphone colorimetric determination of hydrogen peroxide in real samples based on B, N, and S co-doped carbon dots probe.

In this paper, we report the use of a smartphone and B, N, and S co-doped carbon dots (BNS-CDs) as a promising peroxidase mimic to quantify hydrogen peroxide (H2O2). The synthesized BNS-CDs exhibited excellent peroxidase-like activity to catalyze the reaction of the chromogenic substrate 3,3',5,5'-tetramethylbenzidine (TMB) with H2O2 to generate a blue oxide product (ox-TMB) with maximum absorption at 652 nm. Steady-state kinetic analysis demonstrated that the BNS-CDs showed much higher affinity than natural horseradish peroxidase (HRP) for H2O2 due to their small size and larger specific surface area. A smartphone colorimetric readout device was employed to record the RGB (red green blue) value of the ox-TMB solution via the Android application Color Grab for quantitative detection. A good linear relationship (R2 = 0.9970) between the H2O2 concentration and |R-Rblank| value was obtained in the range of 3-30 µM with a limit of detection (LOD) of 0.8 µM. The current method was successfully applied to determine H2O2 in mouthwash and milk with recoveries of 92.70-108.30%. The developed assay is a promising portable detection platform for H2O2 with good sensitivity and selectivity, simple operation, fast response, and low cost. Graphical abstract.

Urinary orosomucoid 1 protein to creatinine ratio as a potential biomarker for early screening of kidney impairment in type-2 diabetes patients.

BACKGROUND: Early screening of diabetic kidney disease (DKD) remains a major challenge. Our aim was to evaluate the value of urinary orosomucoid 1 protein (UORM1) in early renal impairment screening in type-2 diabetes patients. METHODS: The concentration of UORM1, the UORM1-to-creatinine ratio (UORM1CR), the urinary albumin-to-creatinine ratio (ACR), the alpha-1-microglobulin-to-creatinine ratio (A1MCR) and estimated glomerular filtration rate (eGFR) were measured in 406 type-2 diabetes patients. Any positive values for ACR, A1MCR and/or eGFR were considered as indicative of renal impairment. RESULTS: On average, the levels of UORM1 and UORM1CR were about seven times higher in subjects with renal injury than in those without. Both UORM1 and UORM1CR, when adjusted via logarithm-transformation, were significantly related to ACR, A1MCR and eGFR levels. The highest correlation was observed between UORM1CR and A1MCR (r = 0.85, P < .001). The cut-off values for UORM1 (2.53 mg/L) and UORM1CR (3.69 mg/g) for the early diagnosis of kidney impairment were obtained from receiver operating characteristic curves. UORM1CR obviously had higher diagnostic efficiency corresponding to 83.26% sensitivity and 90.32% specificity than UORM1. Likewise, its sensitivity was higher than those of ACR, A1MCR and eGFR. Bad glycaemic control had the highest risk of increased UORM1CR (odds ratio [OR] = 2.81, P < .001), while high HDL-C (high-density lipoprotein cholesterol) decreased the risk of increased UORM1CR (OR = 0.38, P = .017). CONCLUSION: The UORM1CR (>3.69 mg/g) has the high diagnostic efficiency for the early screening of renal impairment in type-2 diabetes patients. Furthermore, good glycaemic control and high HDL-C might be protective factors against UORM1CR increase.

Dual-emission ratio fluorescent probes based on carbon dots and gold nanoclusters for visual and fluorescent detection of copper ions.

Blue carbon dots (BCDs) and red gold nanoclusters modified by bovine serum albumin (BSA-Au NCs) were selected as luminescent nanomaterials, and the nanohybrid materials were successfully prepared and applied to the fluorescent measurement of copper ions. The prepared ratio fluorescent probe has two emission peaks near 452 and 654 nm under an excitation of 330 nm. The fluorescence intensity was gradually quenched because Au NCs was aggregated in the presence of Cu2+, resulting in a gradation of the fluorescent color from red to pink to purple to blue for visual detection. BCDs have almost the same fluorescence intensity due to their light stability and chemical inertness to Cu2+ and serve as a background reference in the sensing system. Under the optimal condition, the detection limit (LOD) is 16 nM, the linear range is 0.05-1.85 µM, and the coefficient of determination R2 is 0.9987 for copper determination. Compared with other single probes, the ratio fluorescent probe in the current study has good water solubility, low cytotoxicity, and is easy to synthesize. The nanoprobe provides a high-quality and sensitive visible light platform for monitoring copper ions. Graphical abstract.

MKP-5 Relieves Lipotoxicity-Induced Islet ß-Cell Dysfunction and Apoptosis via Regulation of Autophagy.

Mitogen-activated protein kinase phosphatase-5 (MKP-5) is a regulator of extracellular signaling that is known to regulate lipid metabolism. In this study, we found that obesity caused by a high-fat diet (HFD) decreased the expression of MKP-5 in the pancreas and primary islet cells derived from mice. Then, we further investigated the role of MKP-5 in the protection of islet cells from lipotoxicity by modulating MKP-5 expression. As a critical inducer of lipotoxicity, palmitic acid (PA) was used to treat islet ß-cells. We found that MKP-5 overexpression restored PA-mediated autophagy inhibition in Rin-m5f cells and protected these cells from PA-induced apoptosis and dysfunction. Consistently, a lack of MKP-5 aggravated the adverse effects of lipotoxicity. Islet cells from HFD-fed mice were infected using recombinant adenovirus expressing MKP-5 (Ad-MKP-5), and we found that Ad-MKP-5 was able to alleviate HFD-induced apoptotic protein activation and relieve the HFD-mediated inhibition of functional proteins. Notably, HFD-mediated impairments in autophagic flux were restored by Ad-MKP-5 transduction. Furthermore, the autophagy inhibitor 3-methyladenine (3-MA) was used to treat Rin-m5f cells, confirming that the MKP-5 overexpression suppressed apoptosis, dysfunction, inflammatory response, and oxidative stress induced by PA via improving autophagic signaling. Lastly, employing c-Jun amino-terminal kinas (JNK), P38, or extracellular-regulated kinase (ERK) inhibitors, we established that the JNK and P38 MAPK pathways were involved in the MKP-5-mediated apoptosis, dysfunction, and autophagic inhibition observed in islet ß cells in response to lipotoxicity.

Flow-injection chemiluminescence of the luminol-potassium periodate system enhanced by TGA-capped CdTe quantum dots for the determination of theophylline.

The chemiluminescence (CL) behaviour of the luminol-potassium periodate system enhanced by CdTe quantum dots capped with thioglycolic acid (TGA-CdTe QDs) was studied using kinetic experiments, CL spectra, UV-vis absorption spectra and fluorescence spectra. The production of oxygen-containing reactant intermediates (O2 •- and OH• ) in the present CL system was verified by CL. The possible CL mechanism was discussed in detail. Furthermore, theophylline (THP) was determined based on its enhancement of the CL intensity of the CdTe QDs-luminol-potassium periodate system coupled with a flow-injection technique. Under these optimized conditions, the linear range was found to be from 1.0 × 10-8 to 1.0 × 10-5  g/mL with a detection limit of 2.8 × 10-9  g/mL (3σ). The recoveries for the determination of THP in tablets were from 98.2 to 99.6%.

Topotactic Conversion of α-Fe2O3 Nanowires into FeP as a Superior Fluorosensor for Nucleic Acid Detection: Insights from Experiment and Theory.

Nanostructures possess distinct quenching ability toward fluorophores with different emission frequencies and have been intensively used as nanoquenchers for homogeneous nucleic acid detection. Complete understanding of such a sensing system will provide significant guidance for the design of superior sensing materials, which is still lacking. In this Letter, we demonstrate the development of FeP nanowires as a nanoquencher for high-performance fluorescent nucleic acid detection with much superior performance to α-Fe2O3 counterparts. The whole detection process is complete within 1 min, and this fluorosensor presents a detection limit as low as 4 pM with strong discrimination of single-point mutation. Electrochemical tests and density functional theory calculations reveal that FeP NWs are superior in both conductivity for facilitated electron diffusion and hydrogen-evolving catalytic activity for favorable electron depletion, providing further experimental and theoretical insights into the enhanced sensing performance of the FeP nanosensor. Both faster electron transfer kinetics and stronger electron-consuming ability via catalyzed proton reduction enable FeP nanowires to be a superb nucleic acid nanosensor for applications.

In Situ Derived CoB Nanoarray: A High-Efficiency and Durable 3D Bifunctional Electrocatalyst for Overall Alkaline Water Splitting.

The development of efficient bifunctional catalysts for the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) is of extreme importance for future renewable energy systems. This Communication reports the recent finding that room-temperature treatment of CoO nanowire array on Ti mesh by NaBH4 in alkaline media leads to in situ development of CoB nanoparticles on nanowire surface. The resulting self-supported CoB@CoO nanoarray behaves as a 3D bifunctional electrocatalyst with high activity and durability for both HER (<17% current density degradation after 20 h electrolysis) and OER (<14% current density degradation after 20 h electrolysis) with the need of the overpotentials of 102 and 290 mV to drive 50 mA cm-2 in 1.0 m KOH, respectively. Moreover, its two-electrode alkaline water electrolyzer also shows remarkably high durability and only demands a cell voltage of 1.67 V to deliver 50 mA cm-2 water-splitting current with a current density retention of 81% after 20 h electrolysis. This work provides a promising methodology for the designing and fabricating of metal-boride based nanoarray as a high-active water-splitting catalyst electrode for applications.

High-Efficiency and Durable Water Oxidation under Mild pH Conditions: An Iron Phosphate-Borate Nanosheet Array as a Non-Noble-Metal Catalyst Electrode.

It is highly desired but still remains a key challenge to develop iron-based large-surface-area arrays as heterogeneous water oxidation catalysts that perform efficiently and durably under mild pH conditions for solar-to-hydrogen conversion. In this work, we report the in situ derivation of an iron phosphate-borate nanosheet array on carbon cloth (Fe-Pi-Bi/CC) from an iron phosphide nanosheet array via oxidative polarization in a potassium borate (KBi) solution. As a 3D catalyst electrode for water oxidation at mild pH, such a Fe-Pi-Bi/CC shows high activity and strong long-term electrochemical durability, and it only demands an overpotential of 434 mV to drive a geometrical catalytic current density of 10 mA cm-2 with maintenance of its activity for at least 20 h in 0.1 M KBi. This study offers an attractive earth-abundant catalyst material in water-splitting devices toward the large-scale production of hydrogen fuels under benign conditions for application.

High-Performance Electrolytic Oxygen Evolution in Neutral Media Catalyzed by a Cobalt Phosphate Nanoarray.

The topotactic conversion of cobalt phosphide nanoarray on Ti mesh into a cobalt phosphate nanoarray (Co-Pi NA) via oxidative polarization in phosphate-buffered water is presented. As a 3D oxygen evolution reaction (OER) catalyst electrode at neutral pH, the resulting Co-Pi NA/Ti shows exceptionally high catalytic activity and demands an overpotential of only 450 mV to drive a geometrical catalytic current density of 10 mA cm-2 . Notably, this catalyst also shows superior long-term electrochemical stability. The excellent catalytic activity can be attributed to that such 3D nanoarray configuration allows for the exposure of more active sites and the easier diffusion of electrolytes and oxygen.

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Infectious diseases are a great threat to human health. Rapid and accurate detection of pathogens is important in the diagnosis and treatment of infectious diseases. Metagenomics next-generation sequencing (mNGS) is an unbiased and comprehensive approach for detecting all RNA and DNA in a sample. With the development of sequencing and bioinformatics technologies, mNGS is moving from research to clinical application, which opens a new avenue for pathogen detection. Numerous studies have revealed good potential for the clinical application of mNGS in infectious diseases, especially in difficult-to-detect, rare, and novel pathogens. However, there are several hurdles in the clinical application of mNGS, such as: (1) lack of universal workflow validation and quality assurance; (2) insensitivity to high-host background and low-biomass samples; and (3) lack of standardized instructions for mass data analysis and report interpretation. Therefore, a complete understanding of this new technology will help promote the clinical application of mNGS to infectious diseases. This review briefly introduces the history of next-generation sequencing, mainstream sequencing platforms, and mNGS workflow, and discusses the clinical applications of mNGS to infectious diseases and its advantages and disadvantages.

Post-COVID-19 pandemic changes in pertussis incidence among patients with acute respiratory tract infections in Zhejiang, China.

Background: Previous studies have compared the incidence of pertussis before and during the COVID-19 pandemic, finding that public health measures related to COVID-19 contributed to a temporary decline in reported pertussis cases during the pandemic. However, the post-pandemic period has seen a resurgence in respiratory infections, influenced by relaxed health measures and decreased public vigilance. This study investigates the epidemiological dynamics of pertussis among patients with acute respiratory tract infections (ARTI) in Zhejiang Province, China, providing essential reference information for ongoing public health strategies. Methods: This study analyzed multicenter data from January 2023 to May 2024, involving 8,560 patients with ARTI from three hospitals in Zhejiang Province. Inclusion criteria included patients who presented with cough symptoms and were clinically diagnosed with either acute upper respiratory tract infections (URTI) or acute lower respiratory tract infections (LRTI), and who had undergone at least one Bordetella pertussis DNA test. The study analyzed the epidemiological changes of pertussis positivity rates and their associations with time, age, gender, and diagnosis types (URTI and LRTI). Results: From January 2023 to May 2024, the positivity rate and testing number for pertussis among patients with ARTI generally showed a gradual increasing pattern. In March 2024, the positivity rate reached its peak at 31.58%, followed by a weekly decline. The overall positivity rate was 23.59%, with no significant differences observed between genders. Pertussis incidence was higher in patients with LRTI (24.49%) compared to those with URTI (18.63%, OR = 1.40, 95% CI: 1.20-1.63, p < 0.001) and in outpatients (25.32%) compared to inpatients (6.09%, OR = 4.17, 95% CI: 3.07-5.64, p < 0.001). According to a generalized additive model analysis, there was a wave-shaped, non-linear relationship between age and pertussis incidence, with a relatively high rate observed in the 5 to 17 age group, peaking at age 10 (33.85%). Additionally, the impact of age, patient type, and diagnosis type on the pertussis infection rate varied across different age groups. Conclusion: After the COVID-19 pandemic, the positivity rate of pertussis in Zhejiang Province peaked in early 2024 and then showed a declining pattern. Children and adolescents were particularly affected, emphasizing the need for enhanced vaccination and public health interventions in this population.

A non-linear association between low-density lipoprotein cholesterol and the risk of diabetic kidney disease in patients with type 2 diabetes in China.

Objective: To explore the intrinsic relationship between low-density lipoprotein cholesterol (LDL-C) and diabetic kidney disease (DKD) in patients with type 2 diabetes (T2D) in China. Methods: This cross-sectional study included 1,313 patients with type 2 diabetes treated at the Affiliated Jinhua Hospital of Zhejiang University School of Medicine, located in Jinhua, China. The data were combined from two periods, 2017 and 2020-2021. Participants were categorized into groups with and without DKD. The relationship between LDL-C levels and DKD was evaluated employing logistics regression analysis and restricted cubic spline (RCS) curves. Results: Generally, there was no statistical difference in LDL-C levels between DKD and non-DKD groups, however, a significantly non-linear relationship (Pnon-linear = 0.011) was observed between LDL-C levels and DKD prevalence after adjusting for confounding factors according to the RCS analysis. Two optimal cut-points of 2.97 and 3.61 mmol/L were selected out using random forest algorithm. With the middle LDL-C concentration (2.97-3.61 mmol/L) as the reference, the odds ratios for low (<2.97 mmol/L) and high (>3.61 mmol/L) concentrations were 1.45 (1.08-1.96) and 1.47 (1.01-2.15) respectively, after adjusting for confounding factors in the multivariate analyses. Notably, this association was more pronounced among female participants in the subgroup analyses. Conclusion: A non-linear association was observed between LDL-C levels and the risk of DKD in patients with T2D in China. LDL-C levels below 2.97 mmol/L may elevate the risk of DKD, particularly in female patients with T2D.

The threshold effect of triglyceride glucose index on diabetic kidney disease risk in patients with type 2 diabetes: unveiling a non-linear association.

Background: Previous studies have confirmed that the triglyceride glucose (TyG) index, recognized as a reliable marker of insulin resistance, is an important risk factor for diabetic kidney disease (DKD). However, it is still unclear whether the DKD risk continues to increase linearly with the elevation of TyG index. This study aimed to thoroughly investigated the intrinsic relationship between TyG index and DKD risk in type 2 diabetes (T2D). Methods: This cross-sectional study included 933 patients with T2D in China, who were categorized into DKD and non-DKD groups and stratified by TyG index levels. Logistic regression analysis identified the independent risk factors for DKD. The association between DKD risk and TyG index was evaluated using the restricted cubic spline (RCS) curves analysis. The R package 'CatPredi' was utilized to determine the optimal cut-off point for the relationship between DKD risk and TyG index, followed by threshold effect analysis. Results: The prevalence of DKD was 33.01%. After adjusting for confounding factors, TyG index was identified as a prominent clinical risk factor for DKD, showing the highest odds ratio (OR 1.57 (1.26 - 1.94), P<0.001). RCS analysis revealed a non-linear relationship with a threshold interval effect between the TyG index and DKD risk. When TyG index ≤ 9.35, DKD risk plateaued at a low level; however, when TyG index > 9.35, DKD risk increased gradually with rising TyG index. Among patients with TyG index > 9.35, each 1-unit increase was associated with a 1.94-fold increased DKD risk (OR=1.94 (1.10 - 3.43), P=0.022). Conclusion: The DKD risk presented a threshold effect with the increase of TyG index, initially stable at a low level, and then gradually rising when the TyG index is above 9.35.