MoleMCL: a multi-level contrastive learning framework for molecular pre-training.

MOTIVATION: Molecular representation learning plays an indispensable role in crucial tasks such as property prediction and drug design. Despite the notable achievements of molecular pre-training models, current methods often fail to capture both the structural and feature semantics of molecular graphs. Moreover, while graph contrastive learning has unveiled new prospects, existing augmentation techniques often struggle to retain their core semantics. To overcome these limitations, we propose a gradient-compensated encoder parameter perturbation approach, ensuring efficient and stable feature augmentation. By merging enhancement strategies grounded in attribute masking and parameter perturbation, we introduce MoleMCL, a new MOLEcular pre-training model based on multi-level contrastive learning. RESULTS: Experimental results demonstrate that MoleMCL adeptly dissects the structure and feature semantics of molecular graphs, surpassing current state-of-the-art models in molecular prediction tasks, paving a novel avenue for molecular modeling. AVAILABILITY AND IMPLEMENTATION: The code and data underlying this work are available in GitHub at https://github.com/BioSequenceAnalysis/MoleMCL.

Surface-based multimodal protein-ligand binding affinity prediction.

MOTIVATION: In the field of drug discovery, accurately and effectively predicting the binding affinity between proteins and ligands is crucial for drug screening and optimization. However, current research primarily utilizes representations based on sequence or structure to predict protein-ligand binding affinity, with relatively less study on protein surface information, which is crucial for protein-ligand interactions. Moreover, when dealing with multimodal information of proteins, traditional approaches typically concatenate features from different modalities in a straightforward manner without considering the heterogeneity among them, which results in an inability to effectively exploit the complementary between modalities. RESULTS: We introduce a novel multimodal feature extraction (MFE) framework that, for the first time, incorporates information from protein surfaces, 3D structures, and sequences, and uses cross-attention mechanism for feature alignment between different modalities. Experimental results show that our method achieves state-of-the-art performance in predicting protein-ligand binding affinity. Furthermore, we conduct ablation studies that demonstrate the effectiveness and necessity of protein surface information and multimodal feature alignment within the framework. AVAILABILITY AND IMPLEMENTATION: The source code and data are available at https://github.com/Sultans0fSwing/MFE.

Polariton Microfluidics for Nonreciprocal Dragging and Reconfigurable Shaping of Polaritons.

Dielectric environment engineering is an efficient and general approach to manipulating polaritons. Liquids serving as the surrounding media of polaritons have been used to shift polariton dispersions and tailor polariton wavefronts. However, those liquid-based methods have so far been limited to their static states, not fully unleashing the promise offered by the mobility of liquids. Here, we propose a microfluidic strategy for polariton manipulation by merging polaritonics with microfluidics. The diffusion of fluids causes gradient refractive indices over microchannels, which breaks the symmetry of polariton dispersions and realizes the microfluidic analogue to nonreciprocal polariton dragging. Based on polariton microfluidics, we also designed a set of on-chip polaritonic elements to actively shape polaritons, including planar lenses, off-axis lenses, Janus lenses, bends, and splitters. Our strategy expands the toolkit for the manipulation of polaritons at the subwavelength scale and possesses potential in the fields of polariton biochemistry and molecular sensing.

Design, synthesis, and biological evaluation of novel 8-substituted quercetin derivatives targeting the ß­catenin/B-cell lymphoma 9 interaction.

The ß-catenin/B-cell lymphoma 9 (BCL9) protein-protein interaction (PPI) is a potential target for aberrantly active Wnt/ß-catenin signaling which actively participates in initiating and progressing of many cancers. Herein, we discovered novel 8-substituted quercetin derivatives with potential inhibitory activities targeting ß-catenin/BCL9 PPI. Among all the derivatives, compound B4 displayed the most promising PPI inhibitory activity with an IC50 value of 2.25 µM in a competitive fluorescence polarization assay and a KD value of 1.44 µM for the ß-catenin protein. Furthermore, B4 selectively inhibited the growth of colorectal cancer (CRC) cells, suppressed the transactivation of Wnt signaling, and downregulated the expression of oncogenic Wnt target gene. Especially, B4 showed potent anti-CRC activity in vivo with the tumor growth inhibition (TGI) of 75.99 % and regulated the tumor immune microenvironment.

Exploring the role of Hmox1 in ferroptosis and immune infiltration during renal ischemia-reperfusion injury.

Ischemia-reperfusion injury (IRI) is inevitable in kidney transplantations and, as a complex pathophysiological process, it can be greatly impacted by ferroptosis and immune inflammation. Our study aimed to identify the biomarkers of renal IRI (RIRI) and elucidate their relationship with immune infiltration. In this study, the GSE148420 database was used as a training set to analyze differential genes and overlap them with ferroptosis-related genes to identify hub genes using a protein-protein interaction (PPI) network, the least absolute shrinkage and selection operator (LASSO), and random forest algorithm (RFA). We verified the hub gene and ferroptosis-related phenotypes in a verification set and animal experiments involving unilateral IRI with contralateral nephrectomy in rats. Gene set enrichment analysis (GSEA) of single genes was conducted according to the hub gene to predict related endogenous RNAs (ceRNAs) and drugs to establish a network. Finally, we used the Cibersort to analyze immunological infiltration and conducted Spearman's correlation analysis. We identified 5456 differential genes and obtained 26 ferroptosis-related differentially expressed genes. Through PPI, LASSO, and RFA, Hmox1 was identified as the only hub gene and its expression levels were verified using verification sets. In animal experiments, Hmox1 was verified as a key biomarker. GSEA of single genes revealed the seven most related pathways, and the ceRNAs network included 138 mRNAs and miRNAs. We predicted 11 related drugs and their three-dimensional structural maps. Thus, Hmox1 was identified as a key biomarker and regulator of ferroptosis in RIRI and its regulation of ferroptosis was closely related to immune infiltration.

Stealth radome with an ultra-broad transparent window and a high selectivity transition band.

Stealth radome (SR), especially with an ultra-broad and nearly transparent window between two absorption bands, plays a crucial role in stealth techniques, antenna radomes, and so on. However, current devices have the defects of narrow transmission bands, high insertion loss, and wide transition bands between the transmission and absorption bands, which are unfavorable for the stealth of broadband radar and communication systems. In this paper, a novel SR with an ultra-broad and high-efficiency inter-absorption band transparent window is proposed by combining broadband resonance lumped circuits with a multi-layer cascaded frequency-selective surface (FSS). The equivalent circuit model (ECM) and transmission line method (TLM) are provided and analyzed as a guideline for the SR design. The SR consists of a resistive lossy layer loaded with wide passband lumped circuits and two stacked lossless FSS layers to collectively achieve the high selectivity and ultra-broad transmission band. Simulated results indicate that the proposed SR exhibits an ultra-broad passband from 8.2 to 11.2 GHz (31%) with transmission amplitude more than 0.85 and two 90% absorption bands over 6.8-7.8 GHz and 12-13 GHz, and the transition bands at both sides are only 0.4 GHz and 0.8 GHz, respectively. Our findings can stimulate the promising applications of SR in broadband stealth devices with integrated ultra-broad communication capability or in other electromagnetic (EM) compatibility facilities.

Huygens' metasurface-based surface plasmon coupler with near-unit efficiency.

Surface plasmon polaritons (SPPs) and their counterparts at low frequency (i.e., spoof SPPs) have been attracting a lot of attention recently due to their potential application for routing information with high speeds and bandwidth. To further develop integrated plasmonics, a high-efficiency surface plasmon coupler is required for full elimination of the intrinsic scattering and reflection when exciting the highly confined plasmonic modes, but a solution to this challenge has remained elusive so far. To take on this challenge, here we propose a feasible spoof SPP coupler based on a transparent Huygens' metasurface, which is able to realize more than 90% efficiency in near- and far-field experiments. To be specific, electrical and magnetic resonators are designed separately on both sides of the metasurface to satisfy the impedance-matching condition everywhere, leading to full conversion of plane wave propagation into surface wave propagation. Moreover, a well-optimized plasmonic metal which is able to support an eigen SPP is designed. This proposed high-efficiency spoof SPP coupler based on a Huygens' metasurface may pave the way for the development of high-performance plasmonic devices.

Anti-PD-1 antibody increases NK cell cytotoxicity towards nasopharyngeal carcinoma cells in the context of chemotherapy-induced upregulation of PD-1 and PD-L1.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a highly malignant epithelial cancer linked to Epstein-Barr virus (EBV) infection. Tumors are characterized by a lymphomononuclear infiltrate and the number of natural killer (NK) cells in tumors appears to be of prognostic significance. Standard treatment for NPC in adolescents and young adults consists of induction chemotherapy followed by radiochemotherapy. Though survival rates are above 80%, the majority of patients suffer from long-term side-effects, mainly related to radiotherapy. The addition of immunotherapy to induction chemotherapy could improve tumor response. METHODS: We have investigated the killing of NPC cells by NK cells in the context of chemotherapy, using a panel of three nasopharyngeal carcinoma cell lines and a patient-derived xenograft. Cytotoxicity was measured using the calcein-release assay, while the contribution of different checkpoints and signaling pathways to killing was studied by siRNA-mediated gene silencing and chemical inhibitors. RESULTS: Chemotherapeutics cisplatin, 5-fluorouracil and gemcitabine sensitized NPC cells to killing by NK cells. Chemotherapeutics led to upregulation of PD-1 in NK cells and PD-L1 in NPC cells via NF-κB. Inhibition of the PD-L1/PD-1 checkpoint by an anti-PD-1 antibody or siRNA increased NK-cell cytotoxicity towards NPC cells. CONCLUSION: The addition of an anti-PD-1 antibody to chemotherapy in patients with NPC could increase the efficacy of induction chemotherapy. If confirmed in a clinical trial, more efficient induction therapy could allow the dose of radiotherapy to be reduced and thereby diminish severe late effects of such therapy.

RORγt agonist synergizes with CTLA-4 antibody to inhibit tumor growth through inhibition of Treg cells via TGF-ß signaling in cancer.

To date, the overall response rate to checkpoint blockade remains unsatisfactory, partially due to the limited understanding of the tumor immune microenvironment. The retinoic acid-related orphan receptor γt (RORγt) is the key transcription factor of T helper cell 17 (Th17) cells and plays an essential role in tumor immunity. In this study, we used JG-1, a potent and selective small-molecule RORγt agonist to evaluate the therapeutic potential and mechanism of action of targeting RORγt in tumor immunity. JG-1 promotes Th17 cells differentiation and inhibition of regulatory T (Treg) cells differentiation. JG-1 demonstrates robust tumor growth inhibition in multiple syngeneic models and shows a synergic effect with the Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) antibody. In tumors, JG-1 not only promotes Th17 cells differentiation and increases C-C Motif Chemokine Receptor 6 (CCR6)- Chemokine (C-C motif) ligand 20 (CCL20) expression, but also inhibits both the expression of transforming growth factor-ß1 (TGF-ß1) and the differentiation and infiltration of Treg cells. In summary, JG-1 is a lead compound showing a potent activity in vitro and robust tumor growth inhibition in vivo with synergetic effects with anti-CTLA-4.

[Establishment of an Animal Model of Vesicoureteral Reflux Renal Injury through Partial Bladder Outlet Obstruction].

OBJECTIVE: To establish an animal model of reflux renal damage through bladder outlet obstruction. METHODS: Sixty male C57BL/6 mice aged 6-8 weeks were randomly assigned to a control group, a sham operation group, and a partial bladder outlet obstruction (PBOO) group, with 20 mice in each group. Laparotomy were performed on the PBOO mice under anesthesia in order to separate the bladder necks and to perform guided partial ligation of the bladder neck with a metal rod of 0.3 mm diameter. Mice in the sham operation group had laparotomy and had their bladder necks separated without ligation. The control group did not receive any treatment. 7 days after the surgery, 12 surviving mice were randomly selected from each group to observe the general changes of the bladder, ureter, renal pelvis and kidney. Retrograde urography was performed through the bladder. Kidney tissues were extracted for histopathological analysis. The expression levels of Vimentin, proliferating cell nuclear antigen (PCNA) and α-smooth muscle actin (α-SMA) were examined with Western blot, immunohistochemistry and immunofluorescence staining tests, respectively. RESULTS: Compared with the control and sham operation group, the bladder, ureter, and renal pelvis of the mice in the PBOO group were significantly enlarged, vesicoureteral reflux was more obvious, the kidney volume and mass increased ( P<0.001), and renal parenchyma became thinner ( P<0.000 1). Histopathological staining showed glomerular atrophy, renal tubule expansion, tubulointerstitial inflammatory cell infiltration, glomerular basement membrane hyperplasia and obvious interstitial fibrosis. Western blot, immunofluorescence and immunohistochemistry staining showed that the expression levels of Vimentin, PCNA and α-SMA in kidney tissue were elevated ( P<0.000 1). CONCLUSION: After PBOO, the bladder, ureter, and kidney of the mice showed obvious morphological alteration and presented reflux renal fibrosis-like damage. This can be used as an animal model to study the pathological alteration mechanism and therapeutic measures of renal fibrosis caused by bladder outlet obstruction.

Optical axis-driven field discontinuity in a hyperbolic medium.

The altering permittivity tensor of a hyperbolic medium from diagonal to off-diagonal by the constructive manipulation of the optical axis (also called tilted hyperbolic medium) has attracted much interest recently. Here, the electromagnetic field solutions of waves interacting with a tilted hyperbolic medium are established. Detailed calculations reveal that when a transverse magnetic (TM) polarized wave is incident from a tilted hyperbolic medium to a dielectric medium, tangential components of electric fields are expected to be discontinuous at the interface. Extraordinary surface voltages are induced at the inner boundary of the tilted hyperbolic medium, which prevents the reflection of electromagnetic waves. This alternative behavior of induced extraordinary surface voltages enriches the understanding of continuity across the boundary and provides a novel perspective for their realizations among multiple experimental platforms.

Automobile exhaust-derived PM2.5 induces blood-testis barrier damage through ROS-MAPK-Nrf2 pathway in sertoli cells of rats.

Particulate matter with an aerodynamic diameter of less than 2.5 µm (PM2.5) derived from automobile exhaust can lead to serious male spermatogenesis dysfunction, but its specific molecular mechanism is unclear. In this experiment, we focused on the blood-testis barriers (BTB) and explored the intracellular mechanisms underlying the fertility toxicity of PM2.5 originating from automobile exhaust in the primary cultured Sertoli cells(SCs) of rats. After PM2.5 exposure, excessive reactive oxygen species (ROS) and increased apoptosis of SCs were detected. The expression of the BTB related proteins including ZO-1, Occludin, N-cadherin and ß-catenin were significantly decreased and the spatial arrangement of F-actin was completely disordered through Immunofluorescence and Western blots tests. The phosphorylation of Jun N-terminal kinase (JNK), extracellular signal regulatory kinase (ERK), p38 mitogen-activated protein kinase (MAPK) were upregulated and nuclear factor (erythroid-derived 2) -like 2-related factor (Nrf2) was downregulated respectively. However, combined utilization of vitamin C and E were observed to prevent the increase of ROS generation, reduce celluar apoptosis, increase the expression of BTB related proteins, reconstructed the spatial arrangement of F-actin as well as improved the Nrf2 expression and attenuated the phosphorylation of the MAPK kinases and cleaved caspase-3 levels. Furthermore, ERK inhibitor (SCH772984), JNK inhibitor (SP600125) and p38 MAPK inhibitor (SB203580) obviously up-regulated BTB-related proteins expression as well as activated Nrf2 expression at varying degrees, indicating that ROS-MAPKs-Nrf2 is involved in the signaling pathway that leads to PM2.5-induced spermatogenesis dysfunction. These findings indicate that PM2.5 derived from automobile exhaust causes oxidative stress, which in turn causes cellular apoptosis of SCs and damage of the blood-testis barrier, resulting male spermatogenesis dysfunction, in which ROS-MAPK-Nrf-2 pathways may play a key role.

Interferon beta increases NK cell cytotoxicity against tumor cells in patients with nasopharyngeal carcinoma via tumor necrosis factor apoptosis-inducing ligand.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is an EBV-associated neoplasm occurring endemically in Southeast Asia and sporadically all over the world. In children and adolescents, high cure rates have been obtained using chemotherapy, radiochemotherapy and maintenance therapy with interferon beta (IFNß). The mechanism by which IFNß contributes to a low systemic relapse rate has not yet been fully revealed. PATIENTS AND METHODS: NK cells and serum samples from two patients with NPC were analyzed before and at different time points during IFNß therapy, for assessment of TRAIL expression and NK cell cytotoxicity. Cytotoxicity was measured using the calcein release assay and the contribution of different death effector pathways was analyzed using specific inhibitors. RESULTS: Treatment with IFNß induced TRAIL expression on patients' NK cells and increased their cytotoxicity against NPC targets in vitro. NK cell-mediated cytotoxicity was predominately mediated via TRAIL. IFNß also induced the production of soluble TRAIL (sTRAIL) by NK cells and its release upon contact with NPC cells. IFNß treatment increased serum levels of sTRAIL in patients. Moreover, sTRAIL concentrated from patients' serum samples induced apoptosis ex vivo in NPC cells from a patient-derived xenograft. CONCLUSION: Increased cytotoxicity of NK cells against NPC cells and increased serum levels of biologically active TRAIL in patients treated with IFNß could be a means to eliminate micrometastatic disease and explain the low systemic relapse rate in this patient group.

Harnessing graphene-hBN hyperstructure for single-photon sources.

One of the key challenges to move single-photon sources into practical applications is the ability to efficiently extract light from a single quantum emitter while maintaining efficient photon emission. Here, we propose to harness the optical topological transitions of graphene-hBN hyperstructure to engineer the emission from quantum emitters and achieve preferential power extraction. We have designed a hyperstructure, which possesses tunability of spontaneous emission and enhancement of extraction during optical topological transitions from the closed (ellipsoid) isofrequency surface to an open (hyperboloid) isofrequency surface by tuning the chemical potential of graphene. Such an interesting feature relies exclusively on the hyperbolic properties of hBN and tunable behavior of graphene, which is confirmed by detailed calculations and simulations. Remarkably, single-photon sources based on the hyperstructure do not require overmuch microfabrication and they are capable of working at tunable frequency.

Analog of giant magnetoimpedance in magnetized ε-near-zero plasma.

In this Letter, we show that magnetized plasma with properly designed parameters at plasma frequency suffers a large magnetoimpedance change under a moderate external magnetic field. Such an interesting feature can be described as the analog of giant magnetoimpedance (GMI), which is confirmed by detailed calculation. GMI devices based on magnetized ε-near-zero plasma do not require microfabrication, and they are capable of working at tunable frequency, even in terahertz frequency range; more importantly, they can be dynamically controlled by environmental parameters such as temperature and pressure.

Spermatogenesis dysfunction induced by PM2.5 from automobile exhaust via the ROS-mediated MAPK signaling pathway.

Long-term exposure to particulate matter 2.5 (PM2.5) from automobile exhaust impairs spermatogenesis through oxidative stress injury, but the underlying mechanism is unknown. To investigate the toxic mechanism of PM2.5-induced spermatogenesis impairment, we focused on the MAPK signaling pathway. We also examined the effects of treatment with vitamins C and E on spermatogenic function. Male SD rats were divided randomly into three groups: control (0.9% sterilized saline), PM2.5 exposure (20 mg/kg.b.w.), and PM2.5 exposure (20 mg/kg.b.w.) with vitamin intervention (vitamin C, 100 mg/kg.b.w.; vitamin E, 50 mg/kg.b.w.). Male rats showed a marked decline in fertility and decreased sperm quality after PM2.5 exposure. The expression of SOD and Nrf2 was significantly decreased, and that of MDA was increased markedly. The expression of blood-testis barrier-associated proteins, such as ZO-1, occludin, connexin 43, and ß-catenin, was significantly decreased, the Bcl-2/Bax ratio was downregulated, and the cleaved caspase-3 level was increased. Phosphorylation of MAPKs, including ERKs, JNKs, and p38, was upregulated. Treatment with vitamins C and E reversed the damage induced by PM2.5 exposure. These results suggest that PM2.5 from automobile exhaust disrupted spermatogenesis via ROS-mediated MAPK pathways, and that a combined vitamin C and E intervention effectively mitigated toxicity in the male reproductive system.

Dispersion engineering of hyperbolic plasmons in bilayer 2D materials.

Recent progress on anisotropic 2D materials brings new technologies for directional guidance of hyperbolic plasmons. Here, we investigate the plasmonic modes in twisted bilayer 2D materials (e.g., black phosphorous). Calculated dispersion curves show that two hyperbolas split as the twisted angle increases. The topological transition from closed ellipses to open hyperbolas is achieved by varying the frequency, indicating switching between highly directional and omnidirectional plasmons. These findings will provide potential applications of anisotropic 2D materials in the design of tunable field effect transistors and waveguides.

Urban fine particulate matter (PM2.5) exposure destroys blood-testis barrier (BTB) integrity through excessive ROS-mediated autophagy.

CONTEXT: Blood-testis barrier (BTB), constituted by tight junctions (TJs), adherens junctions and gap junctions, is important for spermatogenesis. PM2.5 is known to impair testicular functions and reproduction. However, its effects on BTB and the underlying mechanisms remain obscure. OBJECTIVE: To investigate the roles of autophagy in BTB toxicity induced by PM2.5. MATERIALS AND METHODS: Sprague-Dawley rats were developmentally exposed to normal saline (NS) or PM2.5 with the doses of 9 mg/kg b.w. and 24 mg/kg b.w. via intratracheal instillation for seven weeks. Success rate of mating, sperm quality, testicular morphology, expressions of BTB junction proteins and autophagy-related proteins were detected. In addition, expressions of oxidative stress markers were also analyzed. RESULTS: Our results demonstrated that developmental PM2.5 exposure induced noticeable decreased fertility, significantly reduced sperm count, increased sperm abnormality rate and severe testicular damage in histomorphology. The expressions of TJ (such as ZO-1 and occludin), gap junction (such as connexin43) were down-regulated significantly after PM2.5 treatment. Intriguingly, PM2.5 simultaneously increased the number of autophagosomes and the levels of autophagy marker LC3-II and p62, suggesting that the accumulated autophagosomes resulted from impaired autophagy degradation. Moreover, the expressions of HO-1 levels remarkably increased and expression levels of Gpx and SOD were significantly decreased after PM2.5 exposure. Vitamins E and C could alleviate the PM2.5-induced oxidative stress, reverse the autophagy defect and restore the BTB impairment. CONCLUSIONS: Taken together, the results suggest that PM2.5 exposure destroys BTB integrity through excessive ROS-mediated autophagy. Our finding could contribute to a better understanding of PM2.5-induced male reproductive toxicity.

Testicular developmental impairment caused by flutamide-induced and DEHP-induced cryptorchid rat models is mediated by excessive apoptosis and deficient autophagy.

BACKGROUND: Cryptorchidism is a common condition of childhood, and it is known to impair fertility potential. However, the underlying mechanisms remain unclear. METHODS: This study constructed two cryptorchid rat models to investigate the roles of apoptosis and autophagy in testicular impairment induced by cryptorchidism. Pregnant rats were randomly divided into three groups. Group I: non-treated rats were used as controls. Group II: injected with drug Flutamide (Flu) 25 mg/kg/bw/d from gestation day (GD) 11-19. Group III: daily intragastric administration of 750 mg/kg/bw/d di-2-ethylhexylphosphate (DEHP) from GD 7-19. The cubs were feed normally and the testes were excised on postnatal day (PND) 30. RESULTS: Our results demonstrated cryptorchidism models induced noticeable decreased fertility, significantly reduced sperm count, increased sperm abnormality rate, decreased testosterone and severe testicular damage in histomorphology. Intriguingly, the level of apoptosis marker FAS, Cytochrome C and caspase-3 increased in Flu-induced and DEHP-induced groups. DEHP-induced treatment simultaneously increased the number of autophagosomes and the levels of autophagy marker LC3-II and p62. Significant decrease of autophagy gene (LC3-II and p62) expression is found in Flu-induced rats testes. CONCLUSION: Taken together, deficient autophagy is involved in testicular spermatogenesis damage of cryptorchidism rats. And this autophagy defect is caused by deficient degradation.

[Correlation of serum androgen levels with lipid metabolism in middle-aged and elderly men in Zunyi, Guizhou].

OBJECTIVE: To investigate the relationship of the levels of serum androgens with lipid metabolism in middle-aged and elderly men in Zunyi, Guizhou. METHODS: Using the stratified cluster sampling method, we conducted a questionnaire investigation and physical examinations among 437 men in Zunyi City. We divided the subjects into a middle-aged (40－64 ï¼»53.20 ± 7.41ï¼½ years, n = 269) and an elderly group (=≥65 ï¼»70.63 ± 4.66ï¼½ years, n = 168) and collected fasting elbow venous blood samples from them for measuring the levels of total testosterone (TT), sex hormone-binding globulin (SHBG), luteinizing hormone (LH), total cholesterol (TCH), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), calculated free testosterone (cFT), free testosterone index (FTI), and testosterone secretion index (TSI). RESULTS: Compared with the elderly group, the middle-aged males showed significantly lower SHBG, LH, HDL and LDL, and higher cFT, FTI, TSI, TG and TCH (all P < 0.05). TT and SHBG were negatively correlated with TG, TCH, HDL and LDL, while cFT was positively correlated with TCH, and so was FTI with TG, TCH with LDL, and TSI with TCH, HDL and LDL (all P < 0.05), but LH was negatively correlated with TG, TCH and LDL (all P < 0.05). Multivariate linear regression analysis showed that TT and SHBG were negatively correlated with TG, TCH, HDL and LDL, and so was LH with TCH, HDL and LDL (all P < 0.05). CONCLUSIONS: In the middle-aged and elderly men in Zunyi, low concentrations of TT, SHBG and LH were associated with the increased risk of high-TCH and -LDL dyslipidemia, low concentrations of TT and SHBG with that of high-TG dyslipidemia, while high concentrations of TT, SHBG and LH with that of low-HDL dyslipidemia.