Research on the tool influence function characteristics of magnetorheological precession finishing (MRPF).

Magnetorheological finishing (MRF) technology is characterized by its high convergence rate and minimal subsurface damage as advantages. However, the non-Gaussian type tool influence function (TIF) it generates may cause mid-frequency errors and oriented surface texture issues. Magnetorheological precession finishing (MRPF) technology capable of generating Gaussian-like removal functions, lacks a clearly defined removal function model. This study acquired polishing spots in tilted polishing, discrete precession, and continuous precession modes via fixed-point polishing experiments. Using Multiphysics simulation software, stress and velocity distribution in the contact area were simulated. A TIF model, incorporating the synergistic effects of pressure and shear force and multiple influence coefficients, was proposed based on velocity characteristics across the three modes. To accurately predict the TIF, surface topographies with varying coefficients were constructed using this model, analyzing the coefficients' impact on the TIF profile. Optimal coefficients were identified using a least fit error algorithm. Further analysis of the TIF's internal textures revealed that the precession mode of MRPF yields superior surface quality, thereby elucidating the material removal mechanism of MRPF and laying a theoretical groundwork for advancing processing technologies.

High-Performance Self-Powered Photoelectrochemical Ultraviolet Photodetectors Based on an In2O3 Nanocube Film.

Ultraviolet photodetectors (UV PDs) have attracted significant attention due to their wide range of applications, such as underwater communication, biological analysis, and early fire warning systems. Indium oxide (In2O3) is a candidate for developing high-performance photoelectrochemical (PEC)-type UV PDs owing to its high UV absorption and good stability. However, the self-powered photoresponse of the previously reported In2O3-based PEC UV PDs is unsatisfactory. In this work, high-performance self-powered PEC UV PDs were constructed by using an In2O3 nanocube film (NCF) as a photoanode. In2O3 NCF photoanodes were synthesized on FTO by using hydrothermal methods with a calcining process. The influence of the electrolyte concentration, bias potential, and irradiation light on the photoresponse properties was systematically studied. In2O3 NCF PEC UV PDs exhibit outstanding self-powered photoresponses to 365 nm UV light with a high responsivity of 44.43 mA/W and fast response speed (20/30 ms) under zero bias potential, these results are superior to those of previously reported In2O3-based PEC UV PDs. The improved self-powered photoresponse is attributed to the higher photogenerated carrier separation efficiency and faster charge transport of the in-situ grown In2O3 NCF. In addition, these PDs exhibit excellent multicycle stability, maintaining the photocurrent at 98.69% of the initial value after 700 optical switching cycles. Therefore, our results prove the great promise of In2O3 in self-powered PEC UV PDs.

USP3 promotes osteosarcoma progression via deubiquitinating EPHA2 and activating the PI3K/AKT signaling pathway.

Ubiquitin-specific protease 3 (USP3) plays an important role in the progression of various tumors. However, the role of USP3 in osteosarcoma (OS) remains poorly understood. The aim of this study was to explore the biological function of USP3 in OS and the underlying molecular mechanism. We found that OS had higher USP3 expression compared with that of normal bone tissue, and high expression of USP3 was associated with poor prognosis in patients with OS. Overexpression of USP3 significantly increased OS cell proliferation, migration, and invasion. Mechanistically, USP3 led to the activation of the PI3K/AKT signaling pathway in OS by binding to EPHA2 and then reducing its protein degradation. Notably, the truncation mutant USP3-F2 (159-520) interacted with EPHA2, and amino acid 203 was found to play an important role in this process. And knockdown of EPHA2 expression reversed the pro-tumour effects of USP3-upregulating. Thus, our study indicates the USP3/EPHA2 axis may be a novel potential target for OS treatment.

Rab18 maintains homeostasis of subcutaneous adipose tissue to prevent obesity-induced metabolic disorders.

Metabolically healthy obesity refers to obese individuals who do not develop metabolic disorders. These people store fat in subcutaneous adipose tissue (SAT) rather than in visceral adipose tissue (VAT). However, the molecules participating in this specific scenario remain elusive. Rab18, a lipid droplet (LD)-associated protein, mediates the contact between the endoplasmic reticulum (ER) and LDs to facilitate LD growth and maturation. In the present study, we show that the protein level of Rab18 is specifically upregulated in the SAT of obese people and mice. Rab18 adipocyte-specific knockout (Rab18 AKO) mice had a decreased volume ratio of SAT to VAT compared with wildtype mice. When subjected to high-fat diet (HFD), Rab18 AKO mice had increased ER stress and inflammation, reduced adiponectin, and decreased triacylglycerol (TAG) accumulation in SAT. In contrast, TAG accumulation in VAT, brown adipose tissue (BAT) or liver of Rab18 AKO mice had a moderate increase without ER stress stimulation. Rab18 AKO mice developed insulin resistance and systematic inflammation. Rab18 AKO mice maintained body temperature in response to acute and chronic cold induction with a thermogenic SAT, similar to the counterpart mice. Furthermore, Rab18-deficient 3T3-L1 adipocytes were more prone to palmitate-induced ER stress, indicating the involvement of Rab18 in alleviating lipid toxicity. Rab18 AKO mice provide a good animal model to investigate metabolic disorders such as impaired SAT. In conclusion, our studies reveal that Rab18 is a key and specific regulator that maintains the proper functions of SAT by alleviating lipid-induced ER stress.

Energy evolution mechanism of structural surfaces in sandstones with different dips based on the energy principle.

A uniaxial compression test was conducted on sandstone specimens at various inclination angles to determine the energy evolution characteristics during deformation and damage. Based on the principle of minimum energy dissipation, an intrinsic model incorporating the damage threshold was developed to investigate the mechanical properties of sandstone at different inclination angles, and the energy damage evolution during deformation and damage. This study indicated that when the inclination angle of the structural surface remained below 40°, sandstone exhibited varying mechanical properties based on different inclination angles. The peak strain was positively correlated with the inclination angle, whereas the compressive strength and modulus of elasticity showed negative correlations. From an energy perspective, the deformation and damage of sandstone under external loading entail processes of energy input, accumulation, and dissipation. Moreover, higher inclination angles of the structural surface resulted in a smaller absorbed peak strain and a reduced proportion of dissipated energy relative to the energy input, thereby affecting the evolution of energy damage throughout the process. As the inclination angle of the structural surface increased, the absorbed total strain at the peak value decreased, whereas the proportion of the dissipated energy increased. Additionally, the damage threshold and critical value of the rock specimens increased with the inclination angle. The critical value, a composite index comprising the peak strain, compressive strength, and elastic modulus, also increased accordingly. These findings can offer a novel perspective for analyzing geological disasters triggered by fissure zones within underground rock formations.

Cox model risk score to predict survival of intrahepatic cholangiocarcinoma after ultrasound-guided ablation.

PURPOSE: To explore factors associated with overall survival (OS) and progression-free survival (PFS) of intrahepatic cholangiocarcinoma (iCCA) after ultrasound-guided ablation and establish a model for survival risk evaluation. METHODS: Data from 54 patients with 86 iCCAs between August 2008 and October 2022 were retrospectively analyzed. Cox regression were used to analyze the effects of clinical features on OS and PFS. Based on the variables screened by multivariable analysis, a model was established to predict the survival of the patients. Time-dependent receiver operating characteristic (timeROC) curve was constructed to evaluate the performance of this model. The model was further verified by bootstrap validation. The clinical usefulness of the model was evaluated by the decision curve analysis (DCA). RESULTS: During follow up, 39 patients died and 49 patients developed recurrence. Pre-ablation CA199 level > 140 U/ml was the only independent predictor of poor PFS. Age > 70 years, early recurrence, maximal diameter of tumor size > 1.5 cm and pre-ablation CA199 level > 140 U/ml were significantly associated with poor OS. Then a model was established based on the above four variables. The areas under the timeROC curve (AUC) for 1-year, 2-year, 3-year, 5-year were 0.767, 0.854, 0.791 and 0.848, respectively. After bootstrapping for 1000 repetitions, the AUCs were similar to the initial model. DCA also demonstrated that the model had good positive net benefits. CONCLUSION: The established model in this study could predict the survival outcomes of the patients with iCCA after thermal ablation, but further research was needed to validate the results.

Feasibility study on the introduction of Micro-CT technology for the identification of Radix Bupleuri and its adulterants.

Background: Radix Bupleuri, a kind of Chinese herbal medicine with great clinical use, is often confused with its adulterants, and it is difficult to identify it without certain knowledge. The existing identification methods have their own drawbacks, so a new method is needed to realize the identification of Radix Bupleuri and its adulterants. Methods: We used Micro Computed Tomography (Micro-CT) to perform tomography scans on Radix Bupleuri and its adulterants, performed data screening and data correction on the obtained DICOM images, and then applied 3D reconstruction, data augmentation, and ResNext deep learning model for the classification study. Results: The DICOM images after data screening, data correction, and 3D reconstruction can observe the differences in the microstructure of Radix Bupleuri and its adulterants, thus enabling effective classification and analysis. Meanwhile, the accuracy of classification using the ResNext model reached 75%. Conclusion: The results of this study showed that Micro-CT technology is feasible for the authentication of Radix Bupleuri. The pre-processed and 3D reconstructed tomographic images clearly show the microstructure and the difference between Radix Bupleuri and its adulterants without damaging the internal structure of the samples. This study concludes that Micro-CT technology provides important technical support for the reliable identification of Radix Bupleuri and its adulterants, which is expected to play an important role in the quality control and clinical application of herbs.

Postoperative haemoglobin and anaemia-associated ischaemic events after major noncardiac surgery: A sex-stratified cohort study.

STUDY OBJECTIVE: To determine the sex-specific associations between postoperative haemoglobin and mortality or complications reflecting ischaemia or inadequate oxygen supply after major noncardiac surgery. DESIGN: A retrospective cohort study with prospective validation. SETTING: A large university hospital health system in China. PATIENTS: Men and women undergoing elective major noncardiac surgery. INTERVENTIONS AND MEASUREMENTS: The primary exposure was nadir haemoglobin within 48 h after surgery. The outcome of interest was a composite of postoperative mortality or ischaemic events including myocardial injury, acute kidney injury and stroke within hospitalisation. MAIN RESULTS: The study included 26,049 patients (15,757 men and 10,292 women). Low postoperative haemoglobin was a strong predictor of the composite outcome in both sexes, with the risk progressively increasing as the nadir haemoglobin concentration dropped below 130 g l-1 in men and 120 g l-1 in women (adjusted odds ratio [OR] 1.43, 95% CI 1.37-1.50 in men, and OR 1.45, 95% CI 1.35-1.55 in women, per 10 g l-1 decrease in postoperative nadir haemoglobin). Above these sex-specific thresholds, the change of nadir haemoglobin was no longer associated with odds of the composite outcome in either men or women. There was no significant interaction between patient sex and the association between postoperative haemoglobin and the composite outcome (Pinteraction = 0.673). Validation in an external prospective cohort (n = 2120) with systematic postoperative troponin and creatinine measurement confirmed our findings. CONCLUSIONS: Postoperative haemoglobin levels following major noncardiac surgery were nonlinearly associated with ischaemic complications or mortality, without any clinically important interaction with patient sex.

Molecular Stacking Dependent Molecular Oxygen Activation in Supramolecular Polymeric Photocatalysts.

Here, we showed that supramolecular assemblies based on perylene diimides (PDIs) are able to activate molecular oxygen through both the electron transfer and energy transfer pathways, which consequently leads to the formation of superoxide radicals (·O2-) and singlet oxygen species (1O2), respectively. These reactive oxygen species (ROS) can effectively lead to oxidative coupling of benzylamine and oxidation of 2-chloroethyl sulfide (CEES). We have designed and synthesized PDIs with similar molecular structures yet differing by the molecular stacking modes. We found that the photooxidation activities of the PDI supramolecular assemblies are inversely associated with the photoluminescence wavelength difference between the assemblies and the monomers (Δλ) quantitatively, and a smaller Δλ results in a higher catalytic efficiency accordingly. Overall, this work contributes to the design and fabrication of high performance photocatalysts based on metal-free organic materials.

Knockdown of circ_0044226 promotes endoplasmic reticulum stress-mediated autophagy and apoptosis in hepatic stellate cells via miR-4677-3p/SEC61G axis.

Downregulation of circ_0044226 has been demonstrated to reduce pulmonary fibrosis, but the role of circ_0044226 in liver fibrosis remains to be explored. In this work, we found that circ_0044226 expression was upregulated during liver fibrosis. Knockdown of circ_0044226 inhibited proliferation, promoted autophagy and apoptosis of hepatic stellate cell LX-2. Bioinformatic analysis and dual luciferase reporter assays confirmed the interaction between circ_0044226, miR-4677-3p and SEC61G. Mechanistically, knockdown of circ_0044226 suppressed SEC61G expression by releasing miR-4677-3p, thereby enhancing endoplasmic reticulum stress. Overexpression of SEC61G or endoplasmic reticulum stress inhibitor 4-phenylbutiric acid partially reversed the effect of knockdown circ_0044226 on LX-2 cell function. In vivo experiments showed that inhibition of circ_0044226 attenuated CCL4-induced liver fibrosis in mice. These imply that circ_0044226 may be a potential target for the treatment of liver fibrosis.

Enhancing singlet oxygen production of dioxygen activation on the carbon-supported rare-earth oxide nanocluster and rare-earth single atom catalyst to remove antibiotics.

Singlet oxygen (1O2) is extensively employed in the fields of chemical, biomedical and environmental. However, it is still a challenge to produce high- concentration 1O2 by dioxygen activation. Herein, a system of carbon-supported rare-earth oxide nanocluster and single atom catalysts (named as RE2O3/RE-C, RE=La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu, Sc and Y) with similar morphology, structure, and physicochemical characteristic are constructed to activate dissolved oxygen (DO) to enhance 1O2 production. The catalytic activity trends and mechanisms are revealed experimentally and are also proven by theoretical analyses and calculations. The 1O2 generation activity trend is Gd2O3/Gd-C>Er2O3/Er-C>Sm2O3/Sm-C>pristine carbon (C). More than 95.0% of common antibiotics (ciprofloxacin, ofloxacin, norfloxacin and carbamazepine) can be removed in 60 min by Gd2O3/Gd-C. Density functional theory calculations indicate that Gd2O3 nanoclusters and Gd single atoms exhibit the moderate adsorption energy of ·O2- to enhance 1O2 production. This study offers a universal strategy to enhance 1O2 production in dioxygen activation for future application and reveals the natural essence of basic mechanisms of 1O2 production via rare-earth oxide nanoclusters and rare-earth single atoms.

Three-dimensional ultrasound fusion imaging in precise needle placement for thermal ablation of hepatocellular carcinoma.

PURPOSE: To investigate the value of three-dimensional ultrasound fusion imaging (3DUS FI) technique for guiding needle placement in hepatocellular carcinoma (HCC) thermal ablation. METHODS: A total of 57 patients with 60 HCCs with 3DUS FI-guided thermal ablation were retrospectively included in the study. 3DUS volume data of liver were acquired preoperatively by freehand scanning with the tumor and predetermined 5 mm ablative margin automatically segmented. Plan of needle placement was made through a predetermined simulated ablation zone to ensure a 5 mm ablative margin with the coverage rate toward tumor and ablative margin. With real-time ultrasound and 3DUS fusion imaging, ablation needles were placed according to the plan. After ablation, the ablative margin was immediately evaluated by contrast-enhanced ultrasound and 3DUS fusion imaging. The rate of adequate ablative margin, complete response (CR), local tumor progression (LTP), disease-free survival (DFS), and overall survival (OS) was evaluated. RESULTS: According to postoperative contrast-enhanced CT or MR imaging, the complete response rate was 100% (60/60), and 83% of tumors (30/36) achieved adequate ablative margin (>5 mm) three-dimensionally. During the follow-up period of 6.0-42.6 months, LTP occurred in 5 lesions, with 1- and 2-year LTP rates being 7.0% and 9.4%. The 1- and 2-year DFS rates were 76.1% and 65.6%, and 1- and 2-year OS rates were 98.1% and 94.0%. No major complications or ablation-related deaths were observed in any patients. CONCLUSIONS: Three-dimensional ultrasound fusion imaging technique may improve the needle placement of thermal ablation for HCC and reduce the rate of LTP.

Exploration of a Predictive Model for Keloid and Potential Therapeutic Drugs based on Immune Infiltration and Cuproptosis-Related Genes.

The aim of this study was to investigate the correlation between CRGs and immunoinfiltration in keloid, develop a predictive model for keloid occurrence, and explore potential therapeutic drugs. The microarray datasets (GSE7890 and GSE145725) were obtained from Gene Expression Omnibus database to identify the differentially expressed genes (DEGs) between keloid and non-keloid samples. Key genes were identified through immunoinfiltration analysis and DEGs, then analyzed for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes, followed by the identification of protein-protein interaction networks, transcription factors, and miRNAs associated with key genes. Additionally, a logistic regression analysis was performed to develop a predictive model for keloid occurrence, and potential candidate drugs for keloid treatment were identified. Three key genes (FDX1, PDHB, DBT) were identified, showing involvement in acetyl-CoA biosynthesis, mitochondrial matrix, oxidoreductase activity, and the tricarboxylic acid cycle. Immune infiltration analysis suggested the involvement of B cells, Th1 cells, DCs, T helper cells, APC co-inhibition, and T cell co-inhibition in keloid. These genes were used to develop a logistic regression-based nomogram for predicting keloid occurrence with an AUC of 0.859 and good calibration.We identified 32 potential drug molecules and extracted the top 10 compounds based on their P-values, showing promise in targeting key genes and potentially effective against keloid. Our study identified some genes in keloid pathogenesis and potential therapeutic drugs. The predictive model enhance early diagnosis and management. Further research is needed to validate and explore clinical implications.

Mechanism of SO2/H2O enhanced rare earth tailings catalysts in NH3-SCR at medium and high temperature.

Rare earth tailings (RET) NH3-SCR catalysts were prepared by mechanical and microwave activation of a large amount of rare earth tailings after beneficiation of Bayan Ebo rare earth ore. The effects of SO2/H2O on the denitrification performance of the RET catalysts were evaluated by conducting denitrification activity tests, SO2/H2O tolerance tests and in situ DRIFTs mechanistic analysis. The results showed that the denitrification activity was significantly increased in the presence of SO2/H2O. And in situ DRIFTs analysis showed that in the presence of SO2/H2O, SO2 could be adsorbed as SO32- groups by the hydroxyl groups on the catalyst surface and react with SO42- to form S2O72- species. And in the presence of NH3, S2O72- would decompose into unstable SO42- species and SO32- and continue to react cyclically to form S2O72- species, providing the RET catalyst provides more acid sites, facilitating the SCR reaction.

Alleviative effect of quercetin against reproductive toxicity induced by chronic exposure to the mixture of phthalates in male rats.

Phthalates (PEs) are widely used plasticizers in polymer products, and humans are increasingly exposed to them. This study was designed to investigate the alleviative effect of phytochemicals quercetin (Que) against male reproductive toxicity caused by the mixture of three commonly used PEs (MPEs), and further to explore the underlying mechanism. Forty-eight male SD rats were randomly and evenly divided into control group, Que group, MPEs group and MPEs+Que group (n = 12); The oral exposure doses of MPEs and Que were 450 mg/kg/d and 50 mg/kg/d, respectively. After 91 days of continuous intervention, compared with control group, the testes weight, epididymis weight, serum sex hormones, and anogenital distance were significantly decreased in MPEs group (P < 0.05); Testicular histopathological observation showed that all seminiferous tubules were atrophy, leydig cells were hyperplasia, spermatogenic cells growth were arrested in MPEs group. Ultrastructural observation of testicular germ cells showed that the edges of the nuclear membranes were indistinct, and the mitochondria were severely damaged with the cristae disrupted, decreased or even disappeared in MPEs group. Immunohistochemistry and Western blot analysis showed that testicular CYP11A1, CYP17A1 and 17ß-HSD were up-regulated, while StAR, PIWIL1 and PIWIL2 were down-regulated in MPEs group (P < 0.05); However, the alterations of these parameters were restored in MPEs+Que group. The results indicated MPEs disturbed steroid hormone metabolism, and caused male reproductive injuries; whereas, Que could inhibit MPEs' male reproductive toxicity, which might relate to the restored regulation of steroid hormone metabolism.

A new species of genus Crenotia (Bacillariophyta) from Tibet, China.

During the investigation of the freshwater diatoms from Tibet, a monoraphid species was observed from a hot spring near Anduo County, located on a plateau in the central portion of Tibet. This species shares the diagnostic features of Crenotia, such as the valve bent along the transapical axis, striae uniseriate to biseriate from centre to the apices and areolae with special structures located at the end of each stria. We compared the morphological characters of this new species with the others in this genus and show it to be new; it is named Crenotiatibetiasp. nov. This species has small valves with slightly protracted ends with nearly capitate apices, lanceolate axial area, central area unilaterally expanded to the margin, striae uniseriate to biseriate, but, in some valves, the striae are only uniseriate. Areolae are round small to irregular in shape and, at the end of each stria, there is a horseshoe-shaped areola present. Observations of developing valves show all the striae begin biseriate, then they become covered by silica to form uniseriate striae. Comparisons are made amongst the species in this genus and with genera assigned to the Achnanthidiaceae.

Aberrant resting-state co-activation network dynamics in major depressive disorder.

Major depressive disorder (MDD) is a globally prevalent and highly disabling disease characterized by dysfunction of large-scale brain networks. Previous studies have found that static functional connectivity is not sufficient to reflect the complicated and time-varying properties of the brain. The underlying dynamic interactions between brain functional networks of MDD remain largely unknown, and it is also unclear whether neuroimaging-based dynamic properties are sufficiently robust to discriminate individuals with MDD from healthy controls since the diagnosis of MDD mainly depends on symptom-based criteria evaluated by clinical observation. Resting-state functional magnetic resonance imaging (fMRI) data of 221 MDD patients and 215 healthy controls were shared by REST-meta-MDD consortium. We investigated the spatial-temporal dynamics of MDD using co-activation pattern analysis and made individual diagnoses using support vector machine (SVM). We found that MDD patients exhibited aberrant dynamic properties (such as dwell time, occurrence rate, transition probability, and entropy of Markov trajectories) in some transient networks including subcortical network (SCN), activated default mode network (DMN), de-activated SCN-cerebellum network, a joint network, activated attention network (ATN), and de-activated DMN-ATN, where some dynamic properties were indicative of depressive symptoms. The trajectories of other networks to deactivated DMN-ATN were more accessible in MDD patients. Subgroup analyses also showed subtle dynamic changes in first-episode drug-naïve (FEDN) MDD patients. Finally, SVM achieved preferable accuracies of 84.69%, 76.77%, and 88.10% in discriminating patients with MDD, FEDN MDD, and recurrent MDD from healthy controls with their dynamic metrics. Our findings reveal that MDD is characterized by aberrant dynamic fluctuations of brain network and the feasibility of discriminating MDD patients using dynamic properties, which provide novel insights into the neural mechanism of MDD.

Microbiota-microglia crosstalk between Blautia producta and neuroinflammation of Parkinson's disease: A bench-to-bedside translational approach.

Parkinson's disease (PD) is intricately linked to abnormal gut microbiota, yet the specific microbiota influencing clinical outcomes remain poorly understood. Our study identified a deficiency in the microbiota genus Blautia and a reduction in fecal short-chain fatty acid (SCFA) butyrate level in PD patients compared to healthy controls. The abundance of Blautia correlated with the clinical severity of PD. Supplementation with butyrate-producing bacterium B. producta demonstrated neuroprotective effects, attenuating neuroinflammation and dopaminergic neuronal death in mice, consequently ameliorating motor dysfunction. A pivotal inflammatory signaling pathway, the RAS-related pathway, modulated by butyrate, emerged as a key mechanism inhibiting microglial activation in PD. The change of RAS-NF-κB pathway in PD patients was observed. Furthermore, B. producta-derived butyrate demonstrated the inhibition of microglial activation in PD through regulation of the RAS-NF-κB pathway. These findings elucidate the causal relationship between specific gut microbiota and PD, presenting a novel microbiota-based treatment perspective for PD.

Organelle proteomic profiling reveals lysosomal heterogeneity in association with longevity.

Lysosomes are active sites to integrate cellular metabolism and signal transduction. A collection of proteins associated with the lysosome mediate these metabolic and signaling functions. Both lysosomal metabolism and lysosomal signaling have been linked to longevity regulation; however, how lysosomes adjust their protein composition to accommodate this regulation remains unclear. Using deep proteomic profiling, we systemically profiled lysosome-associated proteins linked with four different longevity mechanisms. We discovered the lysosomal recruitment of AMP-activated protein kinase and nucleoporin proteins and their requirements for longevity in response to increased lysosomal lipolysis. Through comparative proteomic analyses of lysosomes from different tissues and labeled with different markers, we further elucidated lysosomal heterogeneity across tissues as well as the increased enrichment of the Ragulator complex on Cystinosin-positive lysosomes. Together, this work uncovers lysosomal proteome heterogeneity across multiple scales and provides resources for understanding the contribution of lysosomal protein dynamics to signal transduction, organelle crosstalk, and organism longevity.

Long-term exposure to the mixture of phthalates induced male reproductive toxicity in rats and the alleviative effects of quercetin.

Phthalates (PEs), such as di(2-ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP) and butyl benzyl phthalate (BBP) could cause reproductive and developmental toxicities, while human beings are increasingly exposed to them at low-doses. Phytochemical quercetin (Que) is a flavonoid that has estrogenic effect, anti-inflammatory and anti-oxidant effects. This study was conducted to assess the alleviative effect of Que. on male reproductive toxicity induced by the mixture of three commonly used PEs (MPEs) at low-dose in rats, and explore the underlying mechanism. Male rats were treated with MPEs (16 mg/kg/day) and/or Que. (50 mg/kg/d) for 91 days. The results showed that MPEs exposure caused male reproductive injuries, such as decreased serum sex hormones levels, abnormal testicular pathological structure, increased abnormal sperm rate and changed expressions of PIWIL1 and PIWIL2. Furthermore, MPEs also changed the expression of steroidogenic proteins in steroid hormone metabolism, including StAR, CYP11A1, CYP17A1, 17ß-HSD, CYP19A1. However, the alterations of these parameters were reversed by Que. MPEs caused male reproductive injuries in rats; Que. inhibited MPEs' male reproductive toxicity, which might relate to the improvement of testosterone biosynthesis.