DnaJ/Hsp40 (heat shock protein 40) proteins have been preserved throughout evolution and are important for protein translation, folding, unfolding, translocation, and degradation, primarily by ...stimulating the ATPase activity of chaperone proteins, Hsp70s. Because the ATP hydrolysis is essential for the activity of Hsp70s, DnaJ/Hsp40 proteins actually determine the activity of Hsp70s by stabilizing their interaction with substrate proteins. DnaJ/Hsp40 proteins all contain the J domain through which they bind to Hsp70s and can be categorized into three groups, depending on the presence of other domains. Six DnaJ homologs have been identified in Escherichia coli and 22 in Saccharomyces cerevisiae. Genome-wide analysis has revealed 41 DnaJ/Hsp40 family members (or putative members) in humans. While 34 contain the typical J domains, 7 bear partially conserved J-like domains, but are still suggested to function as DnaJ/ Hsp40 proteins. DnaJA2b, DnaJB1b, DnaJC2, DnaJC20, and DnaJC21 are named for the first time in this review; all other human DnaJ proteins were dubbed according to their gene names, e.g. DnaJA1 is the human protein named after its gene DNAJA1. This review highlights the progress in studying the domains in DnaJ/Hsp40 proteins, introduces the mechanisms by which they interact with Hsp70s, and stresses their functional diversity.
Systemic lupus erythematosus (SLE) is a prototype inflammatory autoimmune disease, characterized by breakdown of immunotolerance to self-antigens. Renal involvement, known as lupus nephritis (LN), is ...one of the leading causes of morbidity and a significant contributor to mortality in SLE. Despite current pathophysiological advances, further studies are needed to fully understand complex mechanisms underlying the development and progression of LN. Transcription factors (TFs) are proteins that regulate the expression of genes and play a crucial role in the development and progression of LN. The mechanisms of TF promoting or inhibiting gene expression are complex, and studies have just begun to reveal the pathological roles of TFs in LN. Understanding TFs in the pathogenesis of LN can provide valuable insights into this disease's mechanisms and potentially lead to the development of targeted therapies for its management. This review will focus on recent findings on TFs in the pathogenesis of LN and newly developed TF-targeted therapy in renal inflammation.
Acquired therapeutic resistance is the major drawback to effective systemic therapies for cancers. Aggressive triple-negative breast cancers (TNBC) develop resistance to chemotherapies rapidly, ...whereas the underlying mechanisms are not completely understood. Here we show that genotoxic treatments significantly increased the expression of miR-181a in TNBC cells, which enhanced TNBC cell survival and metastasis upon Doxorubicin treatment. Consistently, high miR-181a level associated with poor disease free survival and overall survival after treatments in breast cancer patients. The upregulation of miR-181a was orchestrated by transcription factor STAT3 whose activation depended on NF-κB-mediated IL-6 induction in TNBC cells upon genotoxic treatment. Intriguingly, activated STAT3 not only directly bound to MIR181A1 promoter to drive transcription but also facilitated the recruitment of MSK1 to the same region where MSK1 promoted a local active chromatin state by phosphorylating histone H3. We further identified BAX as a direct functional target of miR-181a, whose suppression decreased apoptosis and increased invasion of TNBC cells upon Dox treatment. These results were further confirmed by evidence that suppression of miR-181a significantly enhanced therapeutic response and reduced lung metastasis in a TNBC orthotopic model. Collectively, our data suggested that miR-181a induction had a critical role in promoting therapeutic resistance and aggressive behavior of TNBC cells upon genotoxic treatment. Antagonizing miR-181a may serve as a promising strategy to sensitize TNBC cells to chemotherapy and mitigate metastasis.
The role of autotransplantation in end-stage hepatic alveolar echinococcosis (AE) is unclear. We aimed to present our 15-case experience and propose selection criteria for autotransplantation. All ...patients were considered to have unresectable hepatic AE by conventional resection due to critical invasion to retrohepatic vena cava, hepatocaval region along with three hepatic veins, and the tertiary portal and arterial branches. All patients successfully underwent ex vivo extended right hepatectomy and autotransplantation without intraoperative mortality. The median autograft weight was 706 g (380–1000 g); operative time was 15.5 hours (11.5–20.5 hours); and anhepatic time was 283.8 minutes (180–435 min). Postoperative hospital stay was 32.3 days (12–60 days). Postoperative complication Clavien–Dindo grade IIIa or higher occurred in three patients including one death that occurred 12 days after the surgery due to acute liver failure. One patient was lost to follow-up after the sixth month. Thirteen patients were followed for a median of 21.6 months with no relapse. This is the largest reported series of patients with end-stage hepatic AE treated with liver autotransplantation. The technique requires neither organ donor nor postoperative immunosuppressant. The early postoperative mortality was low with acceptable morbidity. Preoperative precise assessment and strict patient selection are of utmost importance.
We investigated the oxygen-reduction reaction (ORR) on Pd monolayers on various surfaces and on Pd alloys to obtain a substitute for Pt and to elucidate the origin of their activity. The activity of ...Pd monolayers supported on Ru(0001), Rh(111), Ir(111), Pt(111), and Au(111) increased in the following order: Pd/Ru(0001) < Pd/Ir(111) < Pd/Rh(111) < Pd/Au(111) < Pd/Pt(111). Their activity was correlated with their d-band centers, which were calculated using density functional theory (DFT). We found a volcano-type dependence of activity on the energy of the d-band center of Pd monolayers, with Pd/Pt(111) at the top of the curve. The activity of the non-Pt Pd2Co/C alloy electrocatalyst nanoparticles that we synthesized was comparable to that of commercial Pt-containing catalysts. The kinetics of the ORR on this electrocatalyst predominantly involves a four-electron step reduction with the first electron transfer being the rate-determining step. The downshift of the d-band center of the Pd “skin”, which constitutes the alloy surface due to the strong surface segregation of Pd at elevated temperatures, determined its high ORR activity. Additionally, it showed very high methanol tolerance, retaining very high catalytic activity for the ORR at high concentrations of methanol. Provided its stability is satisfactory, this catalyst might possibly replace Pt in fuel-cell cathodes, especially those of direct methanol oxidation fuel cells (DMFCs).
Twenty‐three published proxy temperature series over China spanning the last 2000 years were selected for an uncertainty analysis in five climate regions. Results indicated that, although large ...uncertainties are found for the period prior to the 16th century, high level of consistency were identified in all regions during the recent 500‐years, highlighted by the two cold periods 1620s–1710s and 1800s–1860s, and the warming during the 20th century. The latter started in Tibet, Northwest and Northeast, and migrated to Central East and Southeast. The analysis also indicates that the warming during the 10–14th centuries in some regions might be comparable in magnitude to the warming of the last few decades of the 20th century which was unprecedented within the past 500 years.
Photochemical smog, characterized by high concentrations of ozone (O3) and fine particles (PM2.5) in the atmosphere, has become one of the top environmental concerns in China. Volatile organic ...compounds (VOCs), one of the key precursors of O3 and secondary organic aerosol (SOA) (an important component of PM2.5), have a critical influence on atmospheric chemistry and subsequently affect regional and global climate. Thus, VOCs have been extensively studied in many cities and regions in China, especially in the North China Plain, the Yangtze River Delta and the Pearl River Delta regions where photochemical smog pollution has become increasingly worse over recent decades. This paper reviews the main studies conducted in China on the characteristics and sources of VOCs, their relationship with O3 and SOA, and their removal technology. This paper also provides an integrated literature review on the formulation and implementation of effective control strategies of VOCs and photochemical smog, as well as suggestions for future directions of VOCs study in China.
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•Characteristics and sources of VOCs in China are reviewed.•Relationship of VOCs with O3 and SOA in China are reviewed.•Integrated literature review on the control strategies of VOCs and photochemical smog is provided.•Future directions of VOC study in China are suggested.
ABSTRACT
The physics of baryons in haloes, and their subsequent influence on the total matter phase space, has a rich phenomenology and must be well understood in order to pursue a vast set of ...questions in both cosmology and astrophysics. We use the Cosmology and Astrophysics with MachinE Learning Simulation (Camels) suite to quantify the impact of four different galaxy formation parameters/processes (as well as two cosmological parameters) on the concentration–mass relation, cvir−Mvir. We construct a simulation-informed non-linear model for concentration as a function of halo mass, redshift, and six cosmological/astrophysical parameters. This is done for two galaxy formation models, IllustrisTNG and Simba, using 1000 simulations of each. We extract the imprints of galaxy formation across a wide range in mass $M_{\rm vir}\in 10^{11}, 10^{14.5} \, {\rm M}_\odot \, h^{-1}$ and in redshift z ∈ 0, 6 finding many strong mass- and redshift-dependent features. Comparisons between the IllustrisTNG and Simba results show the astrophysical model choices cause significant differences in the mass and redshift dependence of these baryon imprints. Finally, we use existing observational measurements of cvir−Mvir to provide rough limits on the four astrophysical parameters. Our non-linear model is made publicly available and can be used to include Camels-based baryon imprints in any halo model-based analysis.
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