Effects of low frequency ultrasound treatment on dissolved organic nitrogen removal by biological activated carbon: Critical insights into molecular characteristics, microbial traits, and metabolism.

Drinking water treatment plants (DWTPs) in China that pioneered the biological activated carbon (BAC) process have reached 10 years of operation. There has been a renewed focus on biofiltration and the performance of old BAC filters for dissolved organic nitrogen (DON) has been poor, requiring replacement and regeneration of the BAC. Therefore, it is necessary to explore a cost-effective way to improve the water quality of the old BAC filters. To address this, low frequency ultrasound is proposed to enhance DON removal efficiency by BAC. In this study, bench and pilot tests were conducted to investigate the effect of low frequency ultrasound on DON removal by 10-year BAC. The results indicated that low frequency ultrasound significantly improved the DON removal rate increased from 15.83 % to 85.87 % and considerably inhibited the nitrogenous disinfection by-products (N-DBPs) formation potential, which was attributed to a decrease in the production of lipid-like, carbohydrate-like, and protein/amino sugar-like DON. The biomass on the BAC was significantly reduced after ultrasound treatment, and it decreased from 349.56∼388.98 nmol P/gBAC to 310.12∼377.63 nmol P/gBAC, enabling the biofilm thickness to decrease and the surface to become sparse and porous, which was conducive to oxygen and nutrients transfer. The Rhizobials associated with microbe-derived DON were stripped away during ultrasound treatment, which reduced microbe-derived DON associated with amino acids. Additionally, ultrasound regulated metabolic pathways, including amino acids, tricarboxylic acid (TCA) cycle, and nucleotide metabolism, to improve the osmotic pressure of the biofilm. In short, low frequency ultrasound treatment can enhance BAC biological properties and effectively remove DON and N-DBPs formation potentials, which provides a viable and promising strategy for improving the safety of drinking water in practice.

Development of Luminescent Biosensors for Calprotectin.

Calprotectin, a metal ion-binding protein complex, plays a crucial role in the innate immune system and has gained prominence as a biomarker for various intestinal and systemic inflammatory and infectious diseases, including inflammatory bowel disease (IBD) and tuberculosis (TB). Current clinical testing methods rely on enzyme-linked immunosorbent assays (ELISAs), limiting accessibility and convenience. In this study, we introduce the Fab-Enabled Split-luciferase Calprotectin Assay (FESCA), a novel quantitative method for calprotectin measurement. FESCA utilizes two new fragment antigen binding proteins (Fabs), CP16 and CP17, that bind to different epitopes of the calprotectin complex. These Fabs are fused with split NanoLuc luciferase fragments, enabling the reconstitution of active luciferase upon binding to calprotectin either in solution or in varied immobilized assay formats. FESCA's output luminescence can be measured with standard laboratory equipment as well as consumer-grade cell phone cameras. FESCA can detect physiologically relevant calprotectin levels across various sample types, including serum, plasma, and whole blood. Notably, FESCA can detect abnormally elevated native calprotectin from TB patients. In summary, FESCA presents a convenient, low-cost, and quantitative method for assessing calprotectin levels in various biological samples, with the potential to improve the diagnosis and monitoring of inflammatory diseases, especially in at-home or point-of-care settings.

Harnessing Disparities in Magnetic Microswarms: From Construction to Collaborative Tasks.

Individual differences in size, experience, and task specialization in natural swarms often result in heterogeneity and hierarchy, facilitating efficient and coordinated task accomplishment. Drawing inspiration from this phenomenon, a general strategy is proposed for organizing magnetic micro/nanorobots (MNRs) with apparent differences in size, shape, and properties into cohesive microswarms with tunable heterogeneity, controlled spatial hierarchy, and collaborative tasking capability. In this strategy, disparate magnetic MNRs can be manipulated to show reversible transitions between synchronization and desynchronization by elaborately regulating parameter sets of the rotating magnetic field. Utilizing these transitions, alongside local robust hydrodynamic interactions, diverse heterospecific pairings of disparate magnetic MNRs can be organized into heterogeneous microswarms, and their spatial organization can be dynamically adjusted from egalitarian to leader-follower-like hierarchies on the fly, both in open space and complex microchannels. Furthermore, when specializing the disparate MNRs with distinct functions ("division of labor") such as sensing and drug carrying, they can execute precise drug delivery targeting unknown sites in a collaborative sensing-navigating-cargo dropping sequence, demonstrating significant potential for precise tumor treatment. These findings highlight the critical roles of attribute differences and hierarchical organization in designing efficient swarming micro/nanorobots for biomedical applications.

Exploring the impacts of service life of biological activated carbon on dissolved organic nitrogen removal.

The biological activated carbon (BAC) process has been widely used in drinking water treatment to improve the removal of pollutants, including the precursors of nitrogenous disinfection byproducts (N-DBPs). Nevertheless, old BAC filter effluent DON concentration is heightened, increasing the highly toxic N-DBPs formation potential. Herein, the variation of dissolved organic nitrogen (DON) was comprehensively explored during one backwashing cycle, focusing on four BAC age (0.3, 2, 5, and 10 years) for BAC filters in drinking water. Comparatively, the removal rate of DON by four BAC followed the order 0.3-yr BAC (39.69%-66.96%) >2-yr BAC (10.10%-39.78%) >5-yr BAC (-4.18%-29.63%)>10-yr BAC (-20.88%-19.87%). When at day 7 after backwashing, 10-yr BAC filter effluent increased at least 13.71% of DON and considerably elevated the N-DBPs formation potential, which was attributed to the ultimate production of more various proteins/amino sugars-like compounds by microbes. In comparisons of microbial community between all BAC samples, Rhizobials were more prevalent in 10-yr BAC and could produce microbe-derived DON associated with amino acids. Moreover, microbes regulated metabolic pathways, including amino acid biosynthesis, TCA cycle, purine metabolism, and pyrimidine metabolism, to enhance the adaptive cellular machinery in response to environmental stressors, and therefore accelerated microbial secretion of microbe-derived DON. Structural equation model (SEM) analysis investigated that BAC age had bio-effects on N-DBPs formation potential, which were delivered via the linkage of " BAC age, microbial community, microbial metabolism, and DON molecular characteristics". Our findings demonstrate the necessity of reconsidering the feasibility of BAC filters for long-time operation, which has implications for future N-DBPs precursors control in drinking water.

Exploring the mechanism of the antithrombotic effects of Pueraria lobata and Pueraria lobata var. thomsonii based on network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Pueraria lobata (Willd.) Ohwi and Pueraria lobata var. thomsonii (Benth.) Maesen are nutritious medicine food homology plants that are widely used in the food and health products industry and are excellent natural materials for the development of new health foods, with great potential for domestic and foreign markets. Clinically, P. lobata and P. thomsonii are used to treat coronary heart disease, atherosclerosis, cerebral infarction and other cardiovascular diseases, and antithrombotic actions may be their core effect in the treatment of thrombotic diseases. However, the underlying mechanisms of the antithrombotic properties of P. lobata and P. thomsonii have not been clarified. METHODS: First, P. lobata and P. thomsonii were identified by high-performance liquid chromatography (HPLC). An arteriovenous bypass thrombosis rat model was established. Thrombus dry‒wet weight, platelet accumulation rate and the four coagulation indices, including activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT) and fibrinogen (FIB), were detected in plasma to manifest the P. lobata and P. thomsonii antithrombotic function. Network pharmacology and molecular docking methods were used to obtain key targets and verify reliability. David 6.8 was used for GO and KEGG analyses to explore pathways and potential targets for P. lobata and P. thomsonii antithrombotic functions. Prostaglandin I2 (PGI2), thromboxane A2 (TXA2), cyclooxygenase 2 (COX-2), myeloperoxidase (MPO) and endothelial nitric oxide synthase (eNOS) were tested by enzyme-linked immunosorbent assay (ELISA). RESULTS: The results indicated that P. lobata and P. thomsonii can reduce thrombus dry‒wet weight and platelet accumulation in rats and inhibit TT, APTT, FIB, and PT. A comprehensive network pharmacology approach successfully identified 9 active ingredients in P. lobata and P. thomsonii. The main active ingredients include polyphenols, amino acids and flavonoids. A total of 15 antithrombotic function targets were obtained, including 3 key targets (PTGS2, NOS3, MPO). Pathway analysis showed 10 significant related pathways and 29 biological processes. P. lobata and P. thomsonii inhibited platelet aggregation by upregulating PGI2 and downregulating TXA2, inhibited PTGS2 to reduce inflammation, and increased the level of eNOS to promote vasodilation. In addition, P. lobata and P. thomsonii alleviated oxidative stress by increasing SOD levels and significantly decreasing MDA contents. CONCLUSION: The results of the study further clarify the antithrombotic mechanism of action of P. lobata and P. thomsonii, which provides a scientific basis for the development of new drugs for thrombogenic diseases and lays the foundation for the development of P. lobata and P. thomsonii herbal resources and P. lobata and P. thomsonii health products.

Charting the Chemical Space of Acrylamide-Based Inhibitors of zDHHC20.

Protein S-acylation is a dynamic and reversible lipid post-translational modification that can affect the activity, stability, localization, and interactions of target proteins. Lipid modification occurs on cysteine residues via a thioester bond and in humans is mediated by 23 Asp-His-His-Cys domain-containing protein acyltransferases (DHHC-PATs). The DHHC-PATs have well-known roles in physiology and disease, but much remains to be discovered about their biological function and therapeutic potential. We recently developed cyanomyracrylamide (CMA), an acrylamide-based DHHC inhibitor with key improvements over existing inhibitors. Here we conduct a structure-activity relationship (SAR) study of CMA and its acrylamide derivatives against zDHHC20, the most structurally characterized member of the human DHHC family, and validate the results against the homologous zDHHC2. This SAR maps out the limitations and potential of the acrylamide scaffold, underscoring the need for a bivalent inhibitor and identifying along the way three molecules with activity on par with CMA but with an improved logP.

IP6 reduces colorectal cancer metastasis by mediating the interaction of gut microbiota with host genes.

Inositol hexaphosphate (IP6) is a phytochemical widely found in grains and legumes that plays an anti-cancer role. However, the mechanism underlying the inhibition of colorectal cancer metastasis by IP6 through host genes, gut microbiota, and their interactions remain elusive. In this study, 16S rRNA sequencing was used to study the effect of IP6 on gut microbiota in an orthotopic transplantation model of colorectal cancer mice. The transcriptome was used to study the changes of host genes in metastasis and the relationship with gut microbiota. The results showed that the gut microbiota composition of model mice was significantly different from that of normal mice. The beta diversity partly tended to return to the normal level after IP6 intervention. Especially, Lactobacillus helveticus and Lactococcus lactis were recovered after IP6-treated. Enrichment analysis showed that the enrichment score of the Cytokine-Cytokine receptor interaction signal pathway decreased after IP6 treatment compared to the model group. Further analysis of differentially expressed genes (DEGs) in this pathway showed that IP6 reduced the expression of the Tnfrsf1b gene related to the area of liver metastasis, and the Tnfrsf1b gene was negatively correlated with the relative abundance of Lactobacillus helveticus. Our results presented that host gene, microbiome and their interaction may serve as promising targets for the mechanism of IP6 intervention in colorectal cancer metastasis.

A High-Throughput Fluorescent Turn-On Assay for Inhibitors of DHHC Family Proteins.

As the "writer" enzymes of protein S-acylation, a dynamic and functionally significant post-translational modification (PTM), DHHC family proteins have emerged in the past decade as both key modulators of cellular homeostasis and as drivers of neoplastic, autoimmune, metabolic, and neurological pathologies. Currently, biological and clinical discovery is hampered by the limitations of existing DHHC family inhibitors, which possess poor physicochemical properties and off-target profiles. However, progress in identifying new inhibitory scaffolds has been meager, in part due to a lack of robust in vitro assays suitable for high-throughput screening (HTS). Here, we report the development of palmitoyl transferase probes (PTPs), a novel family of turn-on pro-fluorescent molecules that mimic the palmitoyl-CoA substrate of DHHC proteins. We use the PTPs to develop and validate an assay with an excellent Z'-factor for HTS. We then perform a pilot screen of 1687 acrylamide-based molecules against zDHHC20, establishing the PTP-based HTS assay as a platform for the discovery of improved DHHC family inhibitors.

A comprehensive study of celastrol metabolism in vivo and in vitro using ultra-high-performance liquid chromatography coupled with hybrid triple quadrupole time-of-flight mass spectrometry.

Celastrol has attracted great attention owing to its anti-arthritis, antioxidant, and anticancer activities. Nevertheless, its metabolism in vivo (rats) and in vitro (rat liver microsomes and intestinal flora) has not been comprehensively characterized. In this study, ultra-high-performance liquid chromatography coupled with hybrid triple quadrupole time-of-flight mass spectrometry was used as a rapid and sensitive approach for studying the metabolism of celastrol in vivo and in vitro. A total of 43 metabolites were identified and characterized. These include 26 metabolites in vivo, and 28 metabolites in vitro (nine metabolites in rat liver microsomes and 24 metabolites in rat intestinal flora). Additionally, the celastrol-biotransformation capacity of the intestinal tract was confirmed to exceed that of the liver. Furthermore, the metabolic profile of celastrol is summarised. The information obtained from this study may provide a basis for understanding the pharmacological mechanisms of celastrol and will be beneficial for clinical applications.

Establishment of Multiplex Amplification System of STR Loci in Felis Catus and Its Forensic Application / 法医学杂志

OBJECTIVES@#To construct a Felis catus STR loci multiplex amplification system and to evaluate its application value by testing the technical performance.@*METHODS@#The published Felis catus STR loci data were reviewed and analyzed to select the STR loci and sex identification loci that could be used for Felis catus individual identification and genetic identification. The fluorescent labeling primers were designed to construct the multiplex amplification system. The system was validated for sensitivity, accuracy, balance, stability, species specificity, tissue identity and mixture analysis, and investigated the genetic polymorphisms in 145 unrelated Felis catus samples.@*RESULTS@#Sixteen Felis catus autosomal STR loci and one sex determining region of Y (SRY) were successfully selected, and constructed a multiplex amplification system containing the above loci. The complete profile of all alleles could still be obtained when the amount of DNA template was as low as 0.25 ng. There was no specific amplification peak in other common animal samples. Population genetic surveys showed that total discrimination power (TDP) of the 16 STR loci was 1-3.57×10-20, the cumulative probability of exclusion (CPE) was 1-6.35×10-5 and the cumulative probability of matching was 3.61×10-20.@*CONCLUSIONS@#The Felis catus STR multiplex amplification system constructed in this study is highly sensitive, species-specific, and accurate in typing results, which can provide an effective solution for Felis catus species identification, individual identification and kinship identification in the field of forensic science.

Inhibitors of DHHC family proteins.

Protein S-acylation is a prevalent post-translational protein lipidation that is dynamically regulated by 'writer' protein S-acyltransferases and 'eraser' acylprotein thioesterases. The protein S-acyltransferases comprise 23 aspartate-histidine-histidine-cysteine (DHHC)-containing proteins, which transfer fatty acid acyl groups from acyl-coenzyme A onto protein substrates. DHHC proteins are increasingly recognized as critical regulators of S-acylation-mediated cellular processes and pathology. As our understanding of the importance and breadth of DHHC-mediated biology and pathology expands, so too does the need for chemical inhibitors of this class of proteins. In this review, we discuss the challenges and progress in DHHC inhibitor development, focusing on 2-bromopalmitate, the most commonly used inhibitor in the field, and N-cyanomethyl-N-myracrylamide, a new broad-spectrum DHHC inhibitor. We believe that current and ongoing advances in structure elucidation, mechanistic interrogation, and novel inhibitor design around DHHC proteins will spark innovative strategies to modulate these critical proteins in living systems.

Development of an Acrylamide-Based Inhibitor of Protein S-Acylation.

Protein S-acylation is a dynamic lipid post-translational modification that can modulate the localization and activity of target proteins. In humans, the installation of the lipid onto target proteins is catalyzed by a family of 23 Asp-His-His-Cys domain-containing protein acyltransferases (DHHC-PATs). DHHCs are increasingly recognized as critical players in cellular signaling events and in human disease. However, progress elucidating the functions and mechanisms of DHHC "writers" has been hampered by a lack of chemical tools to perturb their activity in live cells. Herein, we report the synthesis and characterization of cyano-myracrylamide (CMA), a broad-spectrum DHHC family inhibitor with similar potency to 2-bromopalmitate (2BP), the most commonly used DHHC inhibitor in the field. Possessing an acrylamide warhead instead of 2BP's α-halo fatty acid, CMA inhibits DHHC family proteins in cellulo while demonstrating decreased toxicity and avoiding inhibition of the S-acylation eraser enzymes, two of the major weaknesses of 2BP. Our studies show that CMA engages with DHHC family proteins in cells, inhibits protein S-acylation, and disrupts DHHC-regulated cellular events. CMA represents an improved chemical scaffold for untangling the complexities of DHHC-mediated cell signaling by protein S-acylation.

The development and validation of a sensitive HPLC-MS/MS method for the quantitative and pharmacokinetic study of the seven components of Buddleja lindleyana Fort.

Buddleja lindleyana Fort., a traditional Chinese medicine, has demonstrated anti-inflammatory, immunomodulatory, antidementia, neuroprotective, antibacterial, and antioxidant effects. Its flowers, leaves, and roots have been used as traditional Chinese medicines. A simple and rapid high-performance liquid chromatography method coupled with mass spectrometry (HPLC-MS/MS) was applied in the multicomponent determination of Buddleja lindleyana Fort., and the discrepancies in the contents from ten different habitats were analyzed. The present study simultaneously determined the concentrations of seven chemical compounds of Buddleja lindleyana Fort. extract in rat plasma via HPLC-MS/MS, which was applied in the pharmacokinetic (PK) study of Buddleja lindleyana Fort. A C18 column was used for chromatographic separation, and ion acquisition was achieved by multiple-reaction monitoring (MRM) in negative ionization mode. The optimized mass transition ion-pairs (m/z) for quantization were 591.5/282.8 for linarin, 609.4/300.2 for rutin, 284.9/133.0 for luteolin, 300.6/151.0 for quercetin, 268.8/116.9 for apigenin, 283.0/267.9 for acacetin, 623.3/160.7 for acteoside, and 252.2/155.8 for sulfamethoxazole (IS). A double peak appeared in the drug-time curve of apigenin, which was associated with entero-hepatic recirculation. There were discrepancies in the contents of seven chemical compounds from 10 batches of Buddleja lindleyana Fort., which were associated with the growth environments. Herein, the pharmacokinetic parameters of seven analytes in Buddleja lindleyana Fort. extract are summarized. The maximum plasma concentration (C max) of linarin, rutin, luteolin, quercetin, apigenin, acacetin and acteoside were 894.12 ± 9.34 ng mL-1, 130.76 ± 18.33 ng mL-1, 77.37 ± 25.72 ng mL-1, 20.15 ± 24.85 ng mL-1, 146.42 ± 14.88 ng mL-1, 31.92 ± 17.58 ng mL-1, and 649.78 ± 16.42 ng mL-1, respectively. The time to reach C max for linarin, rutin, luteolin, quercetin, apigenin, acacetin, and acteoside were 10, 5, 5, 5, 180, 10 and 10 min, respectively. This is the first report on the simultaneous determination of seven active components for 10 different growing environments and the pharmacokinetic studies of seven active components in rat plasma after the oral administration of Buddleja lindleyana Fort. extract. This study lays the foundation for a better understanding of the absorption mechanism of Buddleja lindleyana Fort., and the evaluation of its clinical application.

Preparation, evaluation and metabolites study in rats of novel Isoginkgetin-loaded TPGS/soluplus mixed nanomicelles.

At present, cancer is one of the most lethal diseases in the world, and researchers are committed to developing effective anticancer drugs. Isoginkgetin (IGG) is a kind of biflavone with the potential to treat cancer due to the features of altering the cell cycle and inhibiting tumor cell infiltration. However, its solubility, absorbability and bioavailability are poor, so in this study, IGG was prepared into mixed nanomicelles and evaluated in vitro and in vivo. After condition optimization, IGG-loaded TPGS/soluplus mixed nanomicelles with particle size of 62.34 ± 1.10 nm, entrapment efficiency of 96.92 ± 0.66% and drug loading of 2.42 ± 0.02% were successfully prepared. The physicochemical properties of the nanomicelles were stable within 60 days, and the cytotoxicity of the nanomicelles was significantly higher than that of IGG. The metabolism results showed that 32 kinds of metabolites of IGG and 21 kinds of IGG-loaded nanomicelles were detected. The metabolites of IGG can only be detected in feces of rats, while the metabolites of IGG-loaded nanomicelles can be detected in plasma, bile, urine and feces. All these indicated that after prepared into nanomicelles, the stability, solubility, cytotoxicity and bioavailability of IGG were increased significantly, which provided a new choice for the development of new drugs.

Site-specific chemoproteomic profiling of targets of glyoxal.

Aim: Advanced glycation end products (AGE) are the biomarkers of aging and diabetes which are formed via reactions between glycating agents and biomacromolecules. However, no proteomic study has been reported to systematically investigate the protein substrates of AGEs. Results: In this paper, we used an aniline-based probe to capture the glyoxal-imine intermediate which is the transition sate of glyoxal-derived AGEs. Combined with the tandem orthogonal proteolysis activity-based protein profiling strategy, we successfully identified 962 lysines modified by glyoxal. Conclusion: Enzymes in glycolysis are heavily modified by glyoxal and our biochemical experiments showed that glyoxal can significantly inhibit the activity of GAPDH and glycolysis. These data indicated that AGEs modifications may contribute to pathological processes through impairing the glycolytic process.

Two Approaches for Evaluating the Effects of Galangin on the Activities and mRNA Expression of Seven CYP450.

Galangin is a marker compound of honey and Alpinia officinarum Hance that exhibits great potential for anti-microbial, anti-diabetic, anti-obesity, anti-tumour and anti-inflammatory applications. Galangin is frequently consumed in combination with common clinical drugs. Here, we evaluated the effects of galangin on cytochrome P450 (CYP)-mediated metabolism, using two different approaches, to predict drug⁻drug interactions. Male Sprague Dawley rats were administered galangin daily for 8 weeks. A "cocktail-probes" approach was employed to evaluate the activities of different CYP450 enzymes. Blood samples of seven probe drugs were analysed using liquid chromatography-tandem mass spectrometry in positive and negative electrospray-ionisation modes. Pharmacokinetic parameters were calculated to identify statistical differences. CYP mRNA-expression levels were investigated in real-time quantitative polymerase chain reaction experiments. The galangin-treated group showed significantly decreased AUC0⁻∞ and Cmax values for CYP1A2, and CYP2B3. The galangin-treated group showed significantly increased AUC0⁻∞ and Cmax values for CYP2C13 and CYP3A1. No significant influences were observed in the pharmacokinetic profiles of CYP2C11, CYP2D4 and CYP2E1. The mRNA-expression results were consistent with the pharmacokinetic results. Thus, CYP450 enzyme activities may be altered by long-term galangin administration, suggesting galangin to be a promising candidate molecule for enhancing oral drug bioavailability and chemoprevention and reversing multidrug resistance.

Effects of Danshen capsules on the pharmacokinetics and pharmacodynamics of clopidogrel in healthy volunteers.

Nowadays, the Herb-drug combination is becoming increasingly popular in China. However, the possible interaction induced by their combination was examined rarely. The aim of this study was to investigate the effect of multi-dose administration of Danshen capsules on clopidogrel pharmacokinetics and pharmacodynamics in healthy volunteers. A sequential, open-label, and two-period pharmacokinetic drug interaction study was designed to compare clopidogrel pharmacokinetic parameters before and after 7 days of administration of Danshen capsules in twenty healthy male volunteers. Co-administration of multiple doses of Danshen capsules caused increases in apparent oral clearance of clopidogrel and its metabolite by 96.5% and 73.7% and apparent volume of distribution by 94.2% and 75.1%, corresponding declines in Cmax by 41.7% and 32.9%, AUC0-t by 50.3% and 41.8%, and AUC0-∞ by 49.3% and 41.5% in human volunteers, respectively. Corresponding pharmacokinetic findings, co-administration of Danshen capsules with clopidogrel decreased the antiplatelet activity compared with individual agents. The results suggested that multiple dose administration of Danshen capsules could induce cytochrome P450 (CYP) isoenzymes, thereby increasing the clearance of clopidogrel. Therefore, caution should be taken when Danshen products containing lipophilic components are used in combination with therapeutic drugs metabolized by CYP3A4.

Quantitative Profiling of Protein Carbonylations in Ferroptosis by an Aniline-Derived Probe.

Ferroptosis is a regulated form of necrotic cell death implicated in carcinogenesis and neurodegeneration that is driven by phospholipid peroxidation. Lipid-derived electrophiles (LDEs) generated during this process can covalently modify proteins ("carbonylation") and affect their functions. Here we report the development of a quantitative chemoproteomic method to profile carbonylations in ferroptosis by an aniline-derived probe. Using the method, we established a global portrait of protein carbonylations in ferroptosis with >400 endogenously modified proteins and for the first time, identified >20 residue sites with endogenous LDE modifications in ferroptotic cells. Specifically, we discovered and validated a novel cysteine site of modification on voltage-dependent anion-selective channel protein 2 (VDAC2) that might play an important role in sensitizing LDE signals and mediating ferroptosis. Our results will contribute to the understanding of ferroptotic signaling and pathogenesis and provide potential biomarkers for ferroptosis detection.

Impact of cancer deaths on life expectancy and potential years of life lost from 1981 to 2015 in Kunshan, Jiangsu province, China / 中华健康管理学杂志

Objective This study aimed to examine temporal trends in all cancer-eliminated life expectancy and potential years of life lost (PYLL) in Kunshan city, Jiangsu province, between 1981 and 2015. Methods Data were collected from the vital records of Kunshan city. Cancer-eliminated life expectancy and PYLL were calculated by sex,and the Chinese population from the year 2000 was used to calculate age-standardized PYLL. Estimated annual percentage changes (APC) and 95% confidence intervals (CI) were used to examine temporal trends in increased cancer-eliminated life expectancy. Results Between 1981 and 2015,there was a significant decrease in age-standardized PYLL among males (APC=-2.31%, 95% CI:-2.51% to-2.11%) and females (APC=-1.91%, 95% CI:-2.26% to-1.56%). However, an increase was found in cancer-eliminated life expectancy in males and females, from 3.23 to 4.72 years in males(APC=2.42%,95% CI:1.64% to 3.20%)and from 1.10 to 2.94 years in females(APC=3.91%, 95% CI: 1.78% to 6.04%). Conclusion An overall decrease in age-standardized PYLL was observed when all cancers were considered,and an increase in cancer-eliminated life expectancy was found, suggesting that premature deaths due to cancers were reduced gradually. However, the negative effects of cancer on the health of the whole population have not been fully alleviated.