Regulation of T7 gp2.5 binding dynamics by its C-terminal tail, template conformation and sequence.

Bacteriophage T7 single-stranded DNA-binding protein (gp2.5) binds to and protects transiently exposed regions of single-stranded DNA (ssDNA) while dynamically interacting with other proteins of the replication complex. We directly visualize fluorescently labelled T7 gp2.5 binding to ssDNA at the single-molecule level. Upon binding, T7 gp2.5 reduces the contour length of ssDNA by stacking nucleotides in a force-dependent manner, suggesting T7 gp2.5 suppresses the formation of secondary structure. Next, we investigate the binding dynamics of T7 gp2.5 and a deletion mutant lacking 21 C-terminal residues (gp2.5-Δ21C) under various template tensions. Our results show that the base sequence of the DNA molecule, ssDNA conformation induced by template tension, and the acidic terminal domain from T7 gp2.5 significantly impact on the DNA binding parameters of T7 gp2.5. Moreover, we uncover a unique template-catalyzed recycling behaviour of T7 gp2.5, resulting in an apparent cooperative binding to ssDNA, facilitating efficient spatial redistribution of T7 gp2.5 during the synthesis of successive Okazaki fragments. Overall, our findings reveal an efficient binding mechanism that prevents the formation of secondary structures by enabling T7 gp2.5 to rapidly rebind to nearby exposed ssDNA regions, during lagging strand DNA synthesis.

Efficacy of intraoperative neuromonitoring (IONM) and intraoperative indocyanine green videoangiography (ICG-VA) during unruptured anterior choroidal artery aneurysm clipping surgery.

OBJECTIVE: The aim of this study was to investigate the efficacy of intraoperative indocyanine green videoangiography (ICG-VA) and intraoperative neuromonitoring (IONM) to prevent postoperative ischemic complications during microsurgical clipping of unruptured anterior choroidal artery (AChA) aneurysms. METHODS: We retrospectively reviewed the clinical and radiological records of all patients who had undergone microsurgical clipping for unruptured AChA aneurysms at our institution between April 2001 and December 2019. We compared the postoperative complication rate of the group for which intraoperative ICG-VA and IONM were utilized (group B; n=324) with that of the group for which intraoperative ICG-VA and IONM were not utilized (group A; n=72). RESULTS: There were no statistically significant differences in demographic data between the two groups. Statistically significant differences were observed in the rate of overall complications (p=0.014) and postoperative ischemic complications related to AChA territory (p=0.039). All the cases (n=4) in group B who had postoperative infarctions related to AChA territory showed false-negative results of intraoperative ICG-VA and IONM. CONCLUSIONS: Preserving the patency of the AChA is essential to minimize postoperative complications. Intraoperative monitoring tools including ICG-VA and IONM can greatly contribute to lowering complication rates. However, their pitfalls and false-negative results should always be considered.

Improved cytosine base editors generated from TadA variants.

Cytosine base editors (CBEs) enable programmable genomic C·G-to-T·A transition mutations and typically comprise a modified CRISPR-Cas enzyme, a naturally occurring cytidine deaminase, and an inhibitor of uracil repair. Previous studies have shown that CBEs utilizing naturally occurring cytidine deaminases may cause unguided, genome-wide cytosine deamination. While improved CBEs that decrease stochastic genome-wide off-targets have subsequently been reported, these editors can suffer from suboptimal on-target performance. Here, we report the generation and characterization of CBEs that use engineered variants of TadA (CBE-T) that enable high on-target C·G to T·A across a sequence-diverse set of genomic loci, demonstrate robust activity in primary cells and cause no detectable elevation in genome-wide mutation. Additionally, we report cytosine and adenine base editors (CABEs) catalyzing both A-to-I and C-to-U editing (CABE-Ts). Together with ABEs, CBE-Ts and CABE-Ts enable the programmable installation of all transition mutations using laboratory-evolved TadA variants with improved properties relative to previously reported CBEs.

Residues located in the primase domain of the bacteriophage T7 primase-helicase are essential for loading the hexameric complex onto DNA.

The T7 primase-helicase plays a pivotal role in the replication of T7 DNA. Using affinity isolation of peptide-nucleic acid crosslinks and mass spectrometry, we identify protein regions in the primase-helicase and T7 DNA polymerase that form contacts with the RNA primer and DNA template. The contacts between nucleic acids and the primase domain of the primase-helicase are centered in the RNA polymerase subdomain of the primase domain, in a cleft between the N-terminal subdomain and the topoisomerase-primase fold. We demonstrate that residues along a beta sheet in the N-terminal subdomain that contacts the RNA primer are essential for phage growth and primase activity in vitro. Surprisingly, we found mutations in the primase domain that had a dramatic effect on the helicase. Substitution of a residue conserved in other DnaG-like enzymes, R84A, abrogates both primase and helicase enzymatic activities of the T7 primase-helicase. Alterations in this residue also decrease binding of the primase-helicase to ssDNA. However, mass photometry measurements show that these mutations do not interfere with the ability of the protein to form the active hexamer.

Comparative Study of Autophagy in Oxaliplatin-Sensitive and Resistant SNU-C5 Colon Cancer Cells.

Few studies have evaluated the role of autophagy in the development of oxaliplatin (OXT) resistance in colon cancer cells. In this study, we compared the role of autophagy between SNU-C5 colon cancer cells and OXT-resistant SNU-C5 (SNU-C5/OXTR) cells. At the same concentration of OXT, the cytotoxicity of OXT or apoptosis was significantly reduced in SNU-C5/OXTR cells compared with that in SNU-C5 cells. Compared with SNU-C5 cells, SNU-C5/OXTR cells exhibited low levels of autophagy. The expression level of important autophagy proteins, such as autophagy-related protein 5 (Atg5), beclin-1, Atg7, microtubule-associated proteins 1A/1B light chain 3B I (LC3-I), and LC3-II, was significantly lower in SNU-C5/OXTR cells than that in SNU-C5 cells. The expression level of the autophagy-essential protein p62 was also lower in SNU-C5/OXTR cells than in SNU-C5 cells. In SNUC5/ OXTR cells, the production of intracellular reactive oxygen species (ROS) was significantly higher than that in SNU-C5 cells, and treatment with the ROS scavenger N-acetylcysteine restored the reduced autophagy levels. Furthermore, the expression of antioxidant-related nuclear factor erythroid 2-related factor 2 transcription factor, heme oxygenase-1, and Cu/Zn superoxide dismutase were also significantly increased in SNU-C5/OXTR cells. These findings suggest that autophagy is significantly reduced in SNU-C5/OXTR cells compared with SNU-C5 cells, which may be related to the production of ROS in OXT-resistant cells.

High Power Generation with Reducing Agents Using Compost Soil as a Novel Electrocatalyst for Ammonium Fuel Cells.

Ammonium toxicity is a significant source of pollution from industrial civilization that is disrupting the balance of natural systems, adversely affecting soil and water quality, and causing several environmental problems that affect aquatic and human life, including the strong promotion of eutrophication and increased dissolved oxygen consumption. Thus, a cheap catalyst is required for power generation and detoxification. Herein, compost soil is employed as a novel electrocatalyst for ammonium degradation and high-power generation. Moreover, its effect on catalytic activity and material performances is systematically optimized and compared by treating it with various reducing agents, including potassium ferricyanide, ferrocyanide, and manganese dioxide. Ammonium fuel was supplied to the compost soil ammonium fuel cell (CS-AFC) at concentrations of 0.1, 0.2, and 0.3 g/mL. The overall results show that ferricyanide affords a maximum power density of 1785.20 mW/m2 at 0.2 g/mL fuel concentration. This study focuses on high-power generation for CS-AFC. CS-AFCs are sustainable for many hours without any catalyst deactivation; however, they need to be refueled at regular intervals (every 12 h). Moreover, CS-AFCs afford the best performance when ferricyanide is used as the electron acceptor at the cathode. This study proposes a cheap electrocatalyst and possible solutions to the more serious energy generation problems. This study will help in recycling ammonium-rich wastewaters as free fuel for running CS-AFC devices to yield high-power generation with reducing agents for ammonium fuel cell power applications.

Characterization of Korean Distilled Liquor, Soju, Using Chemical, HS-SPME-GC-MS, and Sensory Descriptive Analysis.

The volatile compounds and sensory profiles of 18 different types of distilled soju, chosen with regard to various raw materials and distillation methods (atmospheric vs. vacuum), were explored using headspace solid-phase microextraction (HS-SPME) with gas chromatography-mass spectrometry (GC-MS) and descriptive analysis. General chemical properties such as pH, total acidity (TA), total soluble solids (°Brix), and lactic acid concentration were also determined. A total of 56 volatile compounds, comprising 31 esters, 11 alcohols, 1 acid, 4 aldehydes, 3 ketones, and 6 miscellaneous compounds, were identified. From the principal component analysis (PCA) of the volatile data, samples made using atmospheric distillation such as MSO and PJU showed a clear difference from decompressed distillation samples. Based on the PCA of the sensory data, there was also a clear distinction between samples by their distillation method. To explore relationships among chemical, volatile, and sensory data sets, multiple factor analysis (MFA) was applied. Yeasty and earthy flavors showed a close relationship with 1-nonanol, octatonic acid, and longer-chain esters such as ethyl phenylacetate and ethyl tetradecanoate, and with chemical parameters such as TA, °Brix, and lactic acid.

Utility of sentinel lymph node biopsy in papillary thyroid microcarcinoma.

Purpose: There are many studies on sentinel lymph node (SLN) biopsy in thyroid carcinoma but SLN biopsy (SLNB) in papillary thyroid carcinoma (PTC) remains open to debate. Therefore in this retrospective study, the usefulness of SLNB in thyroid carcinoma patients who had micro-PTC without cervical lymphadenopathy was assessed. Methods: SLNB was performed in 114 patients who were diagnosed with micro-PTC in a single lobe without palpable or ultrasound-detected lymph node at the tertiary center between January 2012 and December 2013. After SLNB, all patients underwent total thyroidectomy and central neck dissection or thyroid lobectomy and central neck dissection of the single side. Results: SLNs were identified in 112 of 114 patients with 41 positive SLNs and 71 negative SLNs on intraoperative frozen sections. However, eight negative patients were found to be positive in the final pathology. Sentinel node identification rate and false negative value of SLNB were 98.2% and 11.3%, respectively. In the univariate analysis, higher lymph node metastasis was detected in men than in women. Higher detection number of SLN showed higher probability of lymph node metastasis. Conclusion: SLNB may be helpful in papillary thyroid cancer, especially in male patients. Also, it is useful for the staging of nodal status and clearance of persistent disease.

Sensory and Volatile Profiles of Korean Commercially Distilled Soju Using Descriptive Analysis and HS-SPME-GC-MS.

Volatile compositions and sensory characteristics of 11 commercially distilled soju samples were investigated using headspace solid-phase microextraction (HS-SPME) with gas chromatography-mass spectrometry (GC-MS) and sensory descriptive analysis. A total of 59 major volatile compounds, consisting of 32 esters, 10 alcohols, 2 acids, 5 aldehydes, 3 ketones, 1 hydrocarbon, 1 furan, 2 phenols, and 3 miscellaneous compounds, were identified. From the principal component analysis (PCA) of volatile data, MSJ made by atmospheric distillation showed a clear distinction in volatile compositions compared to that of other samples made by vacuum distillation. Based on PCA of the sensory data determined by a panel of ten judges, MSJ was associated with a large amount of longer chain esters that showed high intensities in bitter taste and yeast/nuruk-related flavor attributes. HYJ, LPJ, and HAJ made with rice as a raw material were associated with lower intensities of the alcohol aroma, while JRJ and OKJ aged in oak barrels were associated with fruit flavor, sweet flavor, and brandy aroma. In the partial least squares regression (PLSR) analysis to see any relationship between volatile and sensory data, longer chain esters like ethyl tetradecanoate, and ethyl hexadecanoate were highly associated with bleach aroma. In contrast, positive correlations were seen with barley aroma and yeast flavor with hexanal, nonanal, benzaldehyde, and 2-methoxy-phenol.

The trajectory of intrahelical lesion recognition and extrusion by the human 8-oxoguanine DNA glycosylase.

Efficient search for DNA damage embedded in vast expanses of the DNA genome presents one of the greatest challenges to DNA repair enzymes. We report here crystal structures of human 8-oxoguanine (oxoG) DNA glycosylase, hOGG1, that interact with the DNA containing the damaged base oxoG and the normal base G while they are nested in the DNA helical stack. The structures reveal that hOGG1 engages the DNA using different protein-DNA contacts from those observed in the previously determined lesion recognition complex and other hOGG1-DNA complexes. By applying molecular dynamics simulations, we have determined the pathways taken by the lesion and normal bases when extruded from the DNA helix and their associated free energy profiles. These results reveal how the human oxoG DNA glycosylase hOGG1 locates the lesions inside the DNA helix and facilitates their extrusion for repair.

Genomic discovery of an evolutionarily programmed modality for small-molecule targeting of an intractable protein surface.

The vast majority of intracellular protein targets are refractory toward small-molecule therapeutic engagement, and additional therapeutic modalities are needed to overcome this deficiency. Here, the identification and characterization of a natural product, WDB002, reveals a therapeutic modality that dramatically expands the currently accepted limits of druggability. WDB002, in complex with the FK506-binding protein (FKBP12), potently and selectively binds the human centrosomal protein 250 (CEP250), resulting in disruption of CEP250 function in cells. The recognition mode is unprecedented in that the targeted domain of CEP250 is a coiled coil and is topologically featureless, embodying both a structural motif and surface topology previously considered on the extreme limits of "undruggability" for an intracellular target. Structural studies reveal extensive protein-WDB002 and protein-protein contacts, with the latter being distinct from those seen in FKBP12 ternary complexes formed by FK506 and rapamycin. Outward-facing structural changes in a bound small molecule can thus reprogram FKBP12 to engage diverse, otherwise "undruggable" targets. The flat-targeting modality demonstrated here has the potential to expand the druggable target range of small-molecule therapeutics. As CEP250 was recently found to be an interaction partner with the Nsp13 protein of the SARS-CoV-2 virus that causes COVID-19 disease, it is possible that WDB002 or an analog may exert useful antiviral activity through its ability to form high-affinity ternary complexes containing CEP250 and FKBP12.

Catalytically inactive T7 DNA polymerase imposes a lethal replication roadblock.

Bacteriophage T7 encodes its own DNA polymerase, the product of gene 5 (gp5). In isolation, gp5 is a DNA polymerase of low processivity. However, gp5 becomes highly processive upon formation of a complex with Escherichia coli thioredoxin, the product of the trxA gene. Expression of a gp5 variant in which aspartate residues in the metal-binding site of the polymerase domain were replaced by alanine is highly toxic to E. coli cells. This toxicity depends on the presence of a functional E. coli trxA allele and T7 RNA polymerase-driven expression but is independent of the exonuclease activity of gp5. In vitro, the purified gp5 variant is devoid of any detectable polymerase activity and inhibited DNA synthesis by the replisomes of E. coli and T7 in the presence of thioredoxin by forming a stable complex with DNA that prevents replication. On the other hand, the highly homologous Klenow fragment of DNA polymerase I containing an engineered gp5 thioredoxin-binding domain did not exhibit toxicity. We conclude that gp5 alleles encoding inactive polymerases, in combination with thioredoxin, could be useful as a shutoff mechanism in the design of a bacterial cell-growth system.

Cytosine base editors with minimized unguided DNA and RNA off-target events and high on-target activity.

Cytosine base editors (CBEs) enable efficient, programmable reversion of T•A to C•G point mutations in the human genome. Recently, cytosine base editors with rAPOBEC1 were reported to induce unguided cytosine deamination in genomic DNA and cellular RNA. Here we report eight next-generation CBEs (BE4 with either RrA3F [wt, F130L], AmAPOBEC1, SsAPOBEC3B [wt, R54Q], or PpAPOBEC1 [wt, H122A, R33A]) that display comparable DNA on-target editing frequencies, whilst eliciting a 12- to 69-fold reduction in C-to-U edits in the transcriptome, and up to a 45-fold overall reduction in unguided off-target DNA deamination relative to BE4 containing rAPOBEC1. Further, no enrichment of genome-wide C•G to T•A edits are observed in mammalian cells following transfection of mRNA encoding five of these next-generation editors. Taken together, these next-generation CBEs represent a collection of base editing tools for applications in which minimized off-target and high on-target activity are required.

Directed evolution of adenine base editors with increased activity and therapeutic application.

The foundational adenine base editors (for example, ABE7.10) enable programmable A•T to G•C point mutations but editing efficiencies can be low at challenging loci in primary human cells. Here we further evolve ABE7.10 using a library of adenosine deaminase variants to create ABE8s. At NGG protospacer adjacent motif (PAM) sites, ABE8s result in ~1.5× higher editing at protospacer positions A5-A7 and ~3.2× higher editing at positions A3-A4 and A8-A10 compared with ABE7.10. Non-NGG PAM variants have a ~4.2-fold overall higher on-target editing efficiency than ABE7.10. In human CD34+ cells, ABE8 can recreate a natural allele at the promoter of the γ-globin genes HBG1 and HBG2 with up to 60% efficiency, causing persistence of fetal hemoglobin. In primary human T cells, ABE8s achieve 98-99% target modification, which is maintained when multiplexed across three loci. Delivered as messenger RNA, ABE8s induce no significant levels of single guide RNA (sgRNA)-independent off-target adenine deamination in genomic DNA and very low levels of adenine deamination in cellular mRNA.

Hamstring Anterior Cruciate Ligament Reconstruction Using an Adjustable-Loop Cortical Suspension Device: Immediate Postoperative Magnetic Resonance Imaging.

The purpose of this study is to determine whether the hamstring grafts are fully inserted into the femoral tunnel with the adjustable loop using immediate postoperative magnetic resonance imaging (MRI) after anterior cruciate ligament (ACL) reconstructions. A total of 62 consecutive patients underwent hamstring ACL reconstruction using an adjustable-loop cortical suspension device for the femoral fixation and the Intrafix sheath and screw for the tibial fixation. Multiplanar reformatted images of 3-T MRI scans were obtained at the 1st postoperative day before weight bearing is initiated in all patients to evaluate the gap (the tunnel-graft gap) between the top of the hamstring graft and top of the femoral tunnel. Postoperative MRI scans showed that the tunnel-graft gap was 1.5 ± 2.7 mm (range, 0-12 mm). In 43 (69.4%) patients, there was no gap between the top of the femoral tunnel and hamstring graft. In 19 (30.6%) patients, there was a gap between the tunnel and graft, and nine patients demonstrated a tunnel-graft gap greater than 5 mm. Immediate postoperative MRI scans demonstrated that an adjustable-loop cortical suspension device may not pull the hamstring graft completely into the femoral tunnel.

Maintenance of Type IV Secretion Function During Helicobacter pylori Infection in Mice.

The Helicobacter pylori type IV secretion system (T4SS) encoded on the cag pathogenicity island (cagPAI) secretes the CagA oncoprotein and other effectors into the gastric epithelium. During murine infection, T4SS function is lost in an immune-dependent manner, typically as a result of in-frame recombination in the middle repeat region of cagY, though single nucleotide polymorphisms (SNPs) in cagY or in other essential genes may also occur. Loss of T4SS function also occurs in gerbils, nonhuman primates, and humans, suggesting that it is biologically relevant and not simply an artifact of the murine model. Here, we sought to identify physiologically relevant conditions under which T4SS function is maintained in the murine model. We found that loss of H. pylori T4SS function in mice was blunted by systemic Salmonella coinfection and completely eliminated by dietary iron restriction. Both have epidemiologic parallels in humans, since H. pylori strains from individuals in developing countries, where iron deficiency and systemic infections are common, are also more often cagPAI+ than strains from developed countries. These results have implications for our fundamental understanding of the cagPAI and also provide experimental tools that permit the study of T4SS function in the murine model.IMPORTANCE The type IV secretion system (T4SS) is the major Helicobacter pylori virulence factor, though its function is lost during murine infection. Loss of function also occurs in gerbils and in humans, suggesting that it is biologically relevant, but the conditions under which T4SS regulation occurs are unknown. Here, we found that systemic coinfection with Salmonella and iron deprivation each promote retention of T4SS function. These results improve our understanding of the cag pathogenicity island (cagPAI) and provide experimental tools that permit the study of T4SS function in the murine model.

Thyrotropin suppression therapy for papillary thyroid carcinoma with a huge recurred neck lymph node.

Differentiated thyroid cancer (DTC) originating from thyroid tissue is affected by thyrotropin (TSH). TSH suppression therapy is usually recommended after thyroidectomy in cases of DTC. A 57-year-old woman who harbored a very huge recurred lymph node underwent TSH suppression therapy because of the risk of surgical complications. After TSH suppression, the huge neck lymph node exhibited a response and decreased in size. She had been followed up for 144 months. TSH suppression therapy could be considered as an alternative treatment option in a recurred DTC patient with a high perioperative risk.

Comparison of Postoperative Tunnel Widening After Hamstring Anterior Cruciate Ligament Reconstructions Between Anatomic and Nonanatomic Femoral Tunnels.

PURPOSE: To evaluate the effect of the location of the femoral tunnel on 3-dimensional (3D) computed tomography (CT) upon the postoperative tunnel widening after anterior cruciate ligament (ACL) reconstructions. METHODS: Inclusion criteria were patients who underwent hamstring ACL reconstructions using an adjustable-loop cortical suspension device, underwent 3D CT at the day after surgery, and were followed for a minimum of 2 years after surgery. Exclusion criteria were patients with combined ligament injury and reinjury after reconstruction. Using 3D CT, the center of the femoral tunnel aperture was located on a standardized grid system. The center of the ACL footprint was defined from the literature. The femoral tunnel location was classified as anatomic if it located within 2 standard deviations of the center position. If it was outside the 2 standard deviations, the tunnel was classified as nonanatomic. The patients were divided into either anatomic or nonanatomic groups. Femoral tunnel angles on both sagittal and coronal planes were measured. Both femoral and tibial tunnels measured on anteroposterior and lateral radiographs at immediate postoperative day and at 2 years after surgery. Postoperative knee stability and patient-reported outcomes were evaluated. RESULTS: There were 37 patients in anatomical group and 52 patients in nonanatomical group among enrolled 87 patients. There were no differences in demographics between the 2 groups. There were no differences in the femoral tunnel angles and postoperative tunnel widening between the 2 groups. A higher position correlated to the femoral tunnel widening at 2 years postoperatively. Postoperative knee stability and patient-reported outcomes showed no statistically significant differences between the 2 groups. CONCLUSIONS: There was no significant difference in postoperative tunnel widening or clinical outcomes between anatomic and nonanatomic femoral tunnel location after hamstring ACL reconstructions. A higher position correlated to the femoral tunnel widening at 2 years postoperatively. LEVEL OF EVIDENCE: Level III, Retrospective comparative study.

Mechanism of DNA Lesion Homing and Recognition by the Uvr Nucleotide Excision Repair System.

Nucleotide excision repair (NER) is an essential DNA repair system distinguished from other such systems by its extraordinary versatility. NER removes a wide variety of structurally dissimilar lesions having only their bulkiness in common. NER can also repair several less bulky nucleobase lesions, such as 8-oxoguanine. Thus, how a single DNA repair system distinguishes such a diverse array of structurally divergent lesions from undamaged DNA has been one of the great unsolved mysteries in the field of genome maintenance. Here we employ a synthetic crystallography approach to obtain crystal structures of the pivotal NER enzyme UvrB in complex with duplex DNA, trapped at the stage of lesion-recognition. These structures coupled with biochemical studies suggest that UvrB integrates the ATPase-dependent helicase/translocase and lesion-recognition activities. Our work also conclusively establishes the identity of the lesion-containing strand and provides a compelling insight to how UvrB recognizes a diverse array of DNA lesions.

CCR2 knockout ameliorates obesity-induced kidney injury through inhibiting oxidative stress and ER stress.

CCL2/CCR2 signaling is believed to play an important role in kidney diseases. Several studies have demonstrated that blocking of CCR2 has a therapeutic effect on kidney diseases. However, the effects of CCR2 knockout on obesity-induced kidney injury remain unclear. We investigated the therapeutic effects and the mechanism of CCL2/CCR2 signaling in obesity-induced kidney injury. We used C57BL/6-CCR2 wild type and C57BL/6-CCR2 knockout mice: Regular diet wild type (RD WT), RD CCR2 knockout (RD KO), High-fat diet WT (HFD WT), HFD CCR2 KO (HFD KO). Body weight of WT mice was significantly increased after HFD. However, the body weight of HFD KO mice was not decreased compared to HFD WT mice. Food intake and calorie showed no significant differences between HFD WT and HFD KO mice. Glucose, insulin, total cholesterol, and triglycerides levels increased in HFD WT mice were decreased in HFD KO mice. Insulin resistance, increased insulin secretion, and lipid accumulation showed in HFD WT mice were improved in HFD KO mice. Increased desmin expression, macrophage infiltration, and TNF-α in HFD mice were reduced in HFD KO mice. HFD-induced albuminuria, glomerular hypertrophy, glomerular basement membrane thickening, and podocyte effacement were restored by CCR2 depletion. HFD-induced elevated expressions of xBP1, Bip, and Nox4 at RNA and protein levels were significantly decreased in HFD KO. Therefore, blockade of CCL2/CCR2 signaling by CCR2 depletion might ameliorate obesity-induced albuminuria through blocking oxidative stress, ER stress, and lipid accumulation.