Anion-Dominated Solvation in Low-Concentration Electrolytes Promotes Inorganic-Rich Interphase Formation in Lithium Metal Batteries.

While the formation of an inorganic-rich solid electrolyte interphase (SEI) plays a crucial role, the persistent challenge lies in the formation of an organic-rich SEI due to the high solvent ratio in low-concentration electrolytes (LCEs), which hinders the achievement of high-performance lithium metal batteries. Herein, by incorporating di-fluoroethylene carbonate (DFEC) as a non-solvating cosolvent, a solvation structure dominated by anions is introduced in the innovative LCE, leading to the creation of a durable and stable inorganic-rich SEI. Leveraging this electrolyte design, the Li||NCM83 cell demonstrates exceptional cycling stability, maintaining 82.85% of its capacity over 500 cycles at 1 C. Additionally, Li||NCM83 cell with a low N/P ratio (≈2.57) and reduced electrolyte volume (30 µL) retain 87.58% of its capacity after 150 cycles at 0.5 C. Direct molecular information is utilized to reveal a strong correlation between solvation structures and reduction sequences, proving the anion-dominate solvation structure can impedes the preferential reduction of solvents and constructs an inorganic-rich SEI. These findings shed light on the pivotal role of solvation structures in dictating SEI composition and battery performance, offering valuable insights for the design of advanced electrolytes for next-generation lithium metal batteries.

The impact of the scale and hierarchical structure of health human resources on the level of medical services-based on China's four major economic regions.

BACKGROUND: Ensuring that the scale and hierarchical structure of health human resources are rational, and that medical services are efficient and fair, is an important task of practical significance. On this basis, examining the impact of health human resources on the level of medical services presents a new and formidable challenge. This study aims to delve into how the scale and hierarchical structure of health human resources in China's four major economic regions affect the fairness and efficiency of medical services, and to identify optimization strategies. METHODS: This study utilizes provincial panel data from China's four major economic regions spanning the years 2009 to 2021. Initially, it provides a statistical description of the current state of health human resources and the level of medical services. Subsequently, it employs a fixed-effects model to analyze the impact of the scale and hierarchical structure of health human resources, as well as their interactive effects, on the fairness and efficiency of medical services, and discusses the interactive mechanisms between medical service fairness and medical service efficiency. Furthermore, after conducting a comprehensive evaluation of the level of medical services using the entropy weight method, it explores the regional heterogeneity and temporal dynamics in the influence of the scale and hierarchical structure of health human resources on the level of medical services. Finally, the study examines the scientific validity and rationality of the research findings through various robustness checks, including the substitution of research variables and models. RESULTS: The study found that the scale of health human resources has a promoting effect on the equity of medical services (ß ≤ 0.643, p ≤ 0.01), but exhibits an inhibitory effect on the efficiency of medical services (ß ≥ -0.079, p ≤ 0.1); the hierarchical structure of health human resources shows a positive impact on both the equity and efficiency of medical services (ßequity ≤ 0.160, p ≤ 0.01; ßefficiency ≤ 0.341, p ≤ 0.05); at the same time, the results indicate that the interactive effect of the scale and hierarchical structure of health human resources promotes equity in medical services (ß = 0.067, p ≤ 0.01), but restricts the efficiency of medical services (ß ≥ -0.039, p ≤ 0.01); the mechanism by which health human resources affect the level of medical services in China's western and northeastern regions is more pronounced than in the central and eastern regions; after the implementation of the "Healthy China 2030" Planning Outline, the role of health human resources in the level of medical services has been strengthened; in the robustness tests, the model remains robust after replacing the core explanatory variables, with R2 maintained between 0.869 and 0.972, and the dynamic GMM model test shows a significant second-order lag in the level of medical services (ßequity ≤ 0.149, p ≤ 0.01; ßefficiency ≤ 0.461, p ≤ 0.01); the channel test results prove that managerial personnel and other technical personnel are key pathways in regulating the impact of medical staff on the level of medical services. CONCLUSION: This study provides an in-depth analysis of the impact of health human resources on the level of medical services, revealing that both the scale and hierarchical structure of health human resources significantly affect the equity and efficiency of medical services. Furthermore, the influence of health human resources on the level of medical services exhibits regional heterogeneity and temporal characteristics. Robustness tests ensure the scientific validity and robustness of the research conclusions. This provides effective references for optimizing the allocation of health human resources and improving the level of medical services.

Efficient Biodegradation of Multiple Aryloxyphenoxypropionate Herbicides by Corynebacterium sp. Z-1 and the Proposed Degradation Mechanism.

Esterases are crucial for aryloxyphenoxypropionate herbicide (AOPP) biodegradation. However, the underlying molecular mechanisms of AOPP biodegradation by esterases are poorly understood. In the current work, Corynebacterium sp. Z-1 was isolated and found to degrade multiple AOPPs, including quizalofop-p-ethyl (QPE), haloxyfop-p-methyl (HPM), fenoxaprop-p-ethyl (FPE), cyhalofop-butyl (CYB), and clodinafop-propargyl (CFP). A novel esterase, QfeH, which catalyzes the cleavage of ester bonds in AOPPs to form AOPP acids, was identified from strain Z-1. The catalytic activities of QfeH toward AOPPs decreased in the following order: CFP > FPE > CYB > QPE > HPM. Molecular docking, computational analyses, and site-directed mutagenesis indicated the catalytic mechanisms of QfeH-mediated degradation of different AOPPs. Notably, the key residue S159 is essential for the activity of QfeH. Moreover, V222Y, T227M, T227A, A271R, and M275K mutants, exhibiting 2.9-5.0 times greater activity than QfeH, were constructed. This study facilitates the mechanistic understanding of AOPPs bioremediation by esterases.

A Gel Polymer Electrolyte with High Uniform Na+ Flux and its Constructed Hybrid Interface Synergistically to Facilitate High-Performance Sodium Batteries.

Sodium metal batteries (SMBs) can be developed on a large scale to achieve low-cost and high-capacity energy storage systems. Gel polymer electrolyte (GPE) can relieve volatilization of liquid electrolyte, adapt to volume changes in electrodes, and better satisfy the requirements of long-term SMBs. Herein, a dense polyurethane-based GPE modified with polyacrylonitrile is synthesized by rapidly swelling two-component polyurethane/polyacrylonitrile electrospun fiber film. Compared to traditional porous GPEs obtained by swelling porous matrixes, the fiber film provides uniform high Na+ flux inside GPE due to its partial solubility property and ability to dissociate salts. Therefore, it can reduce the polarization effect and induce uniform metal deposition under high current in conjunction with its constructed hybrid N/F-containing solid electrolyte interface (SEI) that possesses low ionic diffusion barrier. The study demonstrates that GPE has an ionic conductivity of 1.816 mS cm-1 at 20 °C and an ion transference number of 0.53. The full battery (NVP/GPE/Na) assembled with this GPE and Na3V2(PO4)3 (NVP) cathode shows 90.8% capacity retention rate after 1000 cycles at 10 C. Considering the convenient preparation and outstanding electrochemical performances of the obtained GPE, it can also be matched with other electrodes in the future to expand the application of sodium-based batteries.

Novel Bifunctional Amidase Catalyzing the Degradation of Propanil and Aryloxyphenoxypropionate Herbicides in Rhodococcus sp. C-1.

Propanil residues can contaminate habitats where microbial degradation is predominant. In this study, an efficient propanil-degrading strain C-1 was isolated from paddy and identified as Rhodococcus sp. It can completely degrade 10 µg/L-150 mg/L propanil within 0.33-10 h via the hydrolysis of the amide bond, forming 3,4-dichloroaniline. A novel bifunctional amidase, PamC, was identified in strain C-1. PamC can catalyze the hydrolysis of the amide bond of propanil to produce 3,4-dichloroaniline as well as the hydrolysis of the ester bonds of aryloxyphenoxypropionate herbicides (APPHs, clodinafop-propargyl, cyhalofop-butyl, fenoxaprop-p-ethyl, fluazifop-p-butyl, haloxyfop-p-methyl, and quizalofop-p-ethyl) to form aryloxyphenoxypropionic acids. Molecular docking and site-directed mutagenesis confirmed that the catalytic triad Lys82-Ser157-Ser181 was the active center for PamC to hydrolyze propanil and cyhalofop-butyl. This study presents a novel bifunctional amidase with capabilities for both amide and ester bond hydrolysis and enhances our understanding of the molecular mechanisms underlying the degradation of propanil and APPHs.

Epigenetically associated IGF2BP3 upregulation promotes cell proliferation by regulating E2F1 expression in hepatocellular carcinoma.

RNA-binding proteins (RBPs) are a class of proteins that primarily function by interacting with different types of RNAs and play a critical role in regulating the transcription and translation of cancer-related genes. However, their role in the progression of hepatocellular carcinoma (HCC) remains unclear. In this study, we analyzed RNA sequencing data and the corresponding clinical information of patients with HCC to screen for prognostic RBPs. Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) was identified as an independent prognostic factor for liver cancer. It is upregulated in HCC and is associated with a poor prognosis. Elevated IGF2BP3 expression was validated via immunohistochemical analysis using a tissue microarray of patients with HCC. IGF2BP3 knockdown inhibited the proliferation of Hep3B and HepG2 cells, whereas IGF2BP3 overexpression promoted the expansion of HuH-7 and MHCC97H cells. Mechanistically, IGF2BP3 modulates cell proliferation by regulating E2F1 expression. DNA hypomethylation of the IGF2BP3 gene may increase the expression of IGF2BP3, thereby enhancing cell proliferation in HCC. Therefore, IGF2BP3 may act as a novel prognostic biomarker and a potential therapeutic target for HCC.

TGF-ß1-Induced LINC01094 promotes epithelial-mesenchymal transition in hepatocellular carcinoma through the miR-122-5p/TGFBR2-SAMD2-SMAD3 Axis.

Hepatocellular carcinoma (HCC) is a common malignancy with a poor prognosis. It has been proven that long non-coding RNAs (lncRNAs) play an essential role in regulating HCC progression. However, the involvement of LINC01094 in regulating epithelial-mesenchymal transition (EMT) in HCC remains unclear. LINC01094 expression in HCC patients was retrieved from the Cancer Genome Atlas database. Overexpressing and downregulating LINC01094 were conducted to investigate its biological functions using Hep3B, SNU-387, and HuH-7 cells. Western blotting and morphological observation were performed to study the EMT in HCC cells. Transwell assay was adopted to determine the migration and invasion of HCC cells. The underlying mechanism of competitive endogenous RNAs (ceRNAs) was investigated using bioinformatics analysis, quantitative reverse-transcription polymerase chain reaction, and rescue experiments. Elevated LINC01094 expression was observed in HCC and associated with a poor prognosis. Knockdown of LINC01094 expression in SNU-387 and HuH-7 cells could inhibit migration, invasion, and EMT markers. Overexpression of LINC01094 indicated that LINC01094 promoted EMT via the TGF-ß/SMAD signaling pathway. The bioinformatics analysis revealed that miR-122-5p was a target of LINC01094. The miRWalk database analysis showed that TGFBR2, SMAD2, and SMAD3 were downstream targets of miR-122-5p. Mechanically, LINC01094 acted as a ceRNA that facilitated HCC metastasis by sponging miR-122-5p to regulate the expression of TGFBR2, SMAD2, and SMAD3. Further, TGF-ß1 could enhance the expression of LINC01094, forming a positive feedback loop. TGF-ß1-induced LINC01094 expression promotes HCC cell migration and invasion by targeting the miR-122-5p/TGFBR2-SMAD2-SMAD3 axis. LINC01094 may be a potential prognostic biomarker and therapeutic target for HCC metastasis.

M2 macrophage exosomes promote resistance to sorafenib in hepatocellular carcinoma cells via miR-200c-3p.

OBJECTIVE: Sorafenib is a chemotherapeutic agent used to treat hepatocellular carcinoma (HCC). However, its clinical response rates are often low. Tumour-associated macrophages (TAMs) have been implicated in tumour resistance. The relationship between TAMs-derived exosomes and primary resistance to sorafenib in hepatocellular carcinoma is unclear. METHODS: The study analysed RNA-SEQ data from TCGA-LIHC to explore the relationship between TAMs and sorafenib IC50. THP-1-induced M2 macrophages were used as a model to investigate the relationship between M2 macrophage exosomes and primary resistance to sorafenib in hepatocellular carcinoma cells using apoptosis, colony generation, cell viability and dual luciferase. RESULTS: M2 macrophage score and sorafenib IC50 were positively correlated in hepatocellular carcinoma patients, M2 macrophage exosomes promoted sorafenib resistance in hepatocellular carcinoma cells, and M2-exo-miR-200c-3p facilitated the development of sorafenib resistance in hepatocellular carcinoma cells by mediating the activation of PI3K/AKT. CONCLUSION: We propose and demonstrate for the first time that M2 macrophage exosomes promote sorafenib resistance in hepatocellular carcinoma, providing a new perspective for the clinical treatment of hepatocellular carcinoma patients.

Efficient and harmless removal of insecticide diazinon via the stepwise combination of biodegradation and photodegradation.

Diazinon, an organophosphorus insecticide, is predominantly removed through photodegradation and biodegradation in the environment. However, photodegradation can generate diazoxon, a highly toxic oxidation byproduct, while biodegradation is hard to complete mineralize diazinon, showing limitations in both methods. In this study, we provided an efficient strategy for the complete and harmless removal of diazinon by synergistically employing biodegradation and photodegradation. The diazinon-degrading strain X1 was capable of completely degrading 200 µM of diazinon into 2-isopropyl-6-methyl-4-pyrimidinol (IMP) within 6 h without producing the highly toxic diazoxon. IMP was the only intermediate metabolite in biodegradation process, which cannot be further degraded by strain X1. Through RT-qPCR and prokaryotic expression analyses, the hydrolase OpdB was pinpointed as the key enzyme for diazinon degradation in strain X1. Photodegradation was further used to degrade IMP and a pyridazine ring-opening product of IMP was identified via high resolution mass spectrometry. The acute toxicity of this product to aquatic organisms were 123 times and 6630 times lower than that of diazinon and IMP, respectively. The stepwise application of biodegradation and photodegradation was proved to be a successful approach for the remediation of diazinon and its metabolite IMP. This integrated method ensures the harmless and complete elimination of diazinon and IMP within only 6 h. The research provides a theoretical basis for the efficient and harmless remediation of organophosphorus insecticide residuals in the environment.

Altered counts and mitochondrial mass of peripheral blood leucocytes in patients with chronic hepatitis B virus infection.

Hepatitis B virus (HBV) damages liver cells through abnormal immune responses. Mitochondrial metabolism is necessary for effector functions of white blood cells (WBCs). The aim was to investigate the altered counts and mitochondrial mass (MM) of WBCs by two novel indicators of mitochondrial mass, MM and percentage of low mitochondrial membrane potential, MMPlow%, due to chronic HBV infection. The counts of lymphocytes, neutrophils and monocytes in the HBV infection group were in decline, especially for lymphocyte (p = 0.034) and monocyte counts (p = 0.003). The degraded MM (p = 0.003) and MMPlow% (p = 0.002) of lymphocytes and MM (p = 0.005) of monocytes suggested mitochondrial dysfunction of WBCs. HBV DNA within WBCs showed an extensive effect on mitochondria metabolic potential of lymphocytes, neutrophils and monocytes indicated by MM; hepatitis B e antigen was associated with instant mitochondrial energy supply indicated by MMPlow% of neutrophils; hepatitis B surface antigen, antiviral therapy by nucleos(t)ide analogues and prolonged infection were also vital factors contributing to WBC alterations. Moreover, degraded neutrophils and monocytes could be used to monitor immune responses reflecting chronic liver fibrosis and inflammatory damage. In conclusion, MM combined with cell counts of WBCs could profoundly reflect WBC alterations for monitoring chronic HBV infection. Moreover, HBV DNA within WBCs may be a vital factor in injuring mitochondria metabolic potential.

Unveiling the role of UPF3B in hepatocellular carcinoma: Potential therapeutic target.

RNA-binding proteins can regulate nucleotide metabolism and gene expression. UPF3B regulator of nonsense mediated mRNA decay (UPF3B) exhibits dysfunction in cancers. However, its role in the progression of hepatocellular carcinoma (HCC) is still insufficiently understood. Here, we found that UPF3B was markedly upregulated in HCC samples and associated with adverse prognosis in patients. UPF3B dramatically promoted HCC growth both in vivo and in vitro. Mechanistically, UPF3B was found to bind to PPP2R2C, a regulatory subunit of PP2A, boosting its mRNA degradation and activating the PI3K/AKT/mTOR pathway. E2F transcription factor 6 (E2F6) directly binds to the UPF3B promoter to facilitate its transcription. Together, the E2F6/UPF3B/PPP2R2C axis promotes HCC growth through the PI3K/AKT/mTOR pathway. Hence, it could be a promising therapeutic target for treating HCC.

Surface Gradient Ni-Rich Cathode for Li-Ion Batteries.

Nickel-rich layered oxide cathode material LiNixCoyMnzO2 (NCM) has emerged as a promising candidate for next-generation lithium-ion batteries (LIBs). These cathode materials possess high theoretical specific capacity, fast electron/ion transfer rate, and high output voltage. However, their potential is impeded by interface instability, irreversible phase transition, and the resultant significant capacity loss, limiting their practical application in LIBs. In this work, a simple and scalable approach is proposed to prepare gradient cathode material (M-NCM) with excellent structural stability and rate performance. Taking advantage of the strong coordination of Ni2+ with ammonia and the reduction reaction of KMnO4, the elemental compositions of the Ni-rich cathode are reasonably adjusted. The resulted gradient compositional design plays a crucial role in stabilizing the crystal structure, which effectively mitigates Li/Ni mixing and suppresses unwanted surficial parasitic reactions. As a result, the M-NCM cathode maintains 98.6% capacity after 200 cycles, and a rapid charging ability of 107.5 mAh g-1 at 15 C. Furthermore, a 1.2 Ah pouch cell configurated with graphite anode demonstrates a lifespan of over 500 cycles with only 8% capacity loss. This work provides a simple and scalable approach for the in situ construction of gradient cathode materials via cooperative coordination and deposition reactions.

Efficient and practical in-jar silicone rubber based passive sampling for simultaneous monitoring of emerging fungicides in water and soils.

The occurrence and ecological impacts of emerging fungicides in the environment has gained increasing attention. This study applied an in-jar passive sampling device based on silicone rubber (SR) film to measuring the freely dissolved concentration (Cfree) of 6 current-use fungicides as a critical index of bioavailability in water and soils. The kinetics parameters including SR-water, soil-water, and organic carbon-water partition coefficients and sampling rates of the target fungicides were first attained and characterized well with their physicochemical properties. The in situ and ex situ field deployment in Hefei City provided the assessment of contaminated levels for these fungicides in rivers and soils. The Cfree of triadimefon and azoxystrobin was estimated at 0.54 ± 0.07-17.4 ± 2.5 ng L-1 in Nanfei River and Chao Lake, while triadimefon was only found in Dongpu Reservoir water with Cfree below 0.66 ± 0.04 ng L-1. The results exhibited that the equilibrium duration of 7 d was suitable for water application but a longer interval of 14 d was recommended for soil sampling. This work demonstrated the advantages of the proposed strategy in terms of fast monitoring within 2 weeks and high sensitivity down to detection limits in 0.5-5 ng L-1. The in-jar passive sampling device can be extrapolated to the evaluation for a wide coverage of organic pollutants in water and soils.

Characteristic and mechanism of biological nitrogen and phosphorus removal facilitated by biogenic manganese oxides (BioMnOx) at various concentrations of Mn(II).

Biogenic manganese oxides (BioMnOx) have attracted considerable attention as active oxidants, adsorbents, and catalysts. However, characteristics and mechanisms of nitrification-denitrification in biological redox reactions mediated by different concentrations of BioMnOx are still unclear. Fate of nutrients (e.g., NH4+-N, TP, NO3--N) and COD were investigated through different concentrations of BioMnOx produced by Mn(II) in the moving bed biofilm reactor (MBBR). 34% and 89.2%, 37.8% and 89.8%, 57.3% and 88.9%, and 62.1% and 90.4% of TN and COD by MBBR were synchronously removed in four phases, respectively. The result suggested that Mn(II) significantly improved the performance of simultaneous nitrification and denitrification (SND) and TP removal based on manganese (Mn) redox cycling. Characteristics of glutathione peroxidase (GSH-Px), reactive oxygen species (ROS), and electron transfer system activity (ETSA) were discussed, demonstrating that ROS accumulation reduced the ETSA and GSH-Px activities when Mn(II) concentration increased. Extracellular polymeric substance (EPS) function and metabolic pathway of Mn(II) were explored. Furthermore, effect of cellular components on denitrification was evaluated including BioMnOx performances, indicating that Mn(II) promoted the non-enzymatic action of cell fragments. Finally, mechanism of nitrification and denitrification, denitrifying phosphorus and Mn removal was further elucidated through X-ray photoelectron spectroscopy (XPS), high throughput sequencing, and fourier transform infrared reflection (FTIR). This results can bringing new vision for controlling nutrient pollution in redox process of Mn(II).

Revealing the biological significance of multiple metabolic pathways of chloramphenicol by Sphingobium sp. WTD-1.

Chloramphenicol (CAP) is an antibiotic that commonly pollutes the environment, and microorganisms primarily drive its degradation and transformation. Although several pathways for CAP degradation have been documented in different bacteria, multiple metabolic pathways in the same strain and their potential biological significance have not been revealed. In this study, Sphingobium WTD-1, which was isolated from activated sludge, can completely degrade 100 mg/L CAP within 60 h as the sole energy source. UPLC-HRMS and HPLC analyses showed that three different pathways, including acetylation, hydroxyl oxidation, and oxidation (C1-C2 bond cleavage), are responsible for the metabolism of CAP. Importantly, acetylation and C3 hydroxyl oxidation reduced the cytotoxicity of the substrate to strain WTD-1, and the C1-C2 bond fracture of CAP generated the metabolite p-nitrobenzoic acid (PNBA) to provide energy for its growth. This indicated that the synergistic action of three metabolic pathways caused WTD-1 to be adaptable and able to degrade high concentrations of CAP in the environment. This study deepens our understanding of the microbial degradation pathway of CAP and highlights the biological significance of the synergistic metabolism of antibiotic pollutants by multiple pathways in the same strain.

Efficacy of epigallocatechin gallate (EGCG) and its underlying mechanism in preventing bisphenol-A-induced metabolic disorders in mice.

To investigate the efficacy of epigallocatechin gallate (EGCG) and its underlying mechanism in preventing bisphenol-A-induced metabolic disorders, in this study, a mice model of metabolic disorders induced by BPA was developed to investigate the efficacy and mechanism of EGCG using microbiomes and metabolomics. The results showed that EGCG reduced body weight, liver weight ratio, and triglyceride and total cholesterol levels in mice by decreasing the mRNA expression of genes related to fatty acid synthesis (Elov16) and cholesterol synthesis (CYP4A14) and increasing the mRNA expression of genes related to fatty acid oxidation (Lss) and cholesterol metabolism (Cyp7a1). In addition, EGCG normalized BPA-induced intestinal microbial dysbiosis. Metabolic pathway analysis showed that low-dose EGCG was more effective than high-dose EGCG at affecting the biosynthesis of L-cysteine, glycerophosphorylcholine, and palmitoleic acid. These results provide specific data and a theoretical basis for the risk assessment of BPA and the utilization of EGCG.

New insights into nitrogen removal by divalent iron-enhanced moving bed biofilm reactor: Performance, interfacial interaction and co-occurrence network.

A divalent iron-mediated moving bed biofilm reactor with intermittent aeration was developed to enhance the nitrogen removal at low carbon-to-nitrogen ratios. The study demonstrated thatammonia removal increased from 51 ± 4 % to 79 ± 4 % and nitrate removal increased from 72 ± 5 % to 98 ± 4 % in phases I-IV, and 2-5 mg·L-1 of divalent iron significantly increased the anoxic denitrification process. Divalent iron stimulated the secretion of extracellular polymeric substances, which facilitated the formation of cross-linked network between microbial cells. Furthermore, the cycle between divalent and trivalent iron decreased the energy barrier between the biofilm and the pollutant. The microbial community further revealed that Proteobacteria (relative abundance: 40-48 %) andBacteroidota(relative abundance: 31-37 %) were the dominant phyla, supporting the synchronous nitrification and denitrification processes as well as the lower accumulation of nitrite. In conclusion, iron redox cycling significantly enhanced the nitrogen removal. This study proposes a viable strategy for the efficient treatment of nutrient wastewater.

Sequential release of interacting proteins and Ub-modifying enzymes by disulfide heterotypic ubiquitin reagents.

Heterotypic ubiquitin (Ub) chains have emerged as fundamental components in a wide range of cellular processes. The integrative identification of Ub-interacting proteins (readers) and Ub-modifying enzymes (writers and erasers) that selectively recognize and regulate heterotypic ubiquitination may provide crucial insights into these processes. In this study, we employed the bifunctional molecule-assisted (CAET) strategy to develop a type of disulfide bond-activated heterotypic Ub reagents, which allowed to enrich heterotypic Ub-interacting proteins and modifying enzymes simultaneously. The sequential release of readers which are non-covalently bound and writers or erasers which are covalently conjugated by using urea and reductant, respectively, combined with label-free quantitative (LFQ) MS indicated that these heterotypic Ub reagents would facilitate future investigations into functional roles played by heterotypic Ub chains.

Structure-guided engineering enables E3 ligase-free and versatile protein ubiquitination via UBE2E1.

Ubiquitination, catalyzed usually by a three-enzyme cascade (E1, E2, E3), regulates various eukaryotic cellular processes. E3 ligases are the most critical components of this catalytic cascade, determining both substrate specificity and polyubiquitination linkage specificity. Here, we reveal the mechanism of a naturally occurring E3-independent ubiquitination reaction of a unique human E2 enzyme UBE2E1 by solving the structure of UBE2E1 in complex with substrate SETDB1-derived peptide. Guided by this peptide sequence-dependent ubiquitination mechanism, we developed an E3-free enzymatic strategy SUE1 (sequence-dependent ubiquitination using UBE2E1) to efficiently generate ubiquitinated proteins with customized ubiquitinated sites, ubiquitin chain linkages and lengths. Notably, this strategy can also be used to generate site-specific branched ubiquitin chains or even NEDD8-modified proteins. Our work not only deepens the understanding of how an E3-free substrate ubiquitination reaction occurs in human cells, but also provides a practical approach for obtaining ubiquitinated proteins to dissect the biochemical functions of ubiquitination.

Multiple cystic echinococcosis in abdominal and pelvic cavity treated by surgery with a 4-year follow-up: a case report.

We report a case of a male patient who presented with multiple abdominal and pelvic echinococcosis. The patient had been diagnosed with hepatic echinococcosis for 7 years and developed intermittent distension and discomfort in the upper abdomen after an accidental fall. In recent years, the patient's abdominal distention increased gradually. Computed tomography revealed multiple hydatid cysts in the liver, spleen, abdominal cavity, and pelvic cavity. Abdominal organs were severely compressed, such that he could not eat normally except for a liquid diet. The patient underwent radical surgical resection based on the multi-disciplinary treatment (MDT) and the operation lasted 10 h, nearly 100 hydatid cysts were excised, about 18 liters of cyst fluid and cyst contents were removed, and the patient lost 20 kg of weight after surgery. The operation was successful, but there were still some postoperative complications such as hypovolemic shock, postoperative ascites, postoperative bile leakage. Treatment measures for the patient were anti-infection, antishock, clamping the abdominal drainage tube, and negative pressure abdominal puncture drainage. At follow up the patient's quality of life had been significantly improved with 15 kg weight gain compared to before.