Preparation and anti-tumor activity of paclitaxel silk protein nanoparticles encapsulated by biofilm.

In order to overcome the poor bioavailability of paclitaxel (PTX), in this study, self-assembled paclitaxel silk fibronectin nanoparticles (PTX-SF-NPs) were encapsulated with outer membrane vesicles of Escherichia coli (E. coil), and biofilm-encapsulated paclitaxel silk fibronectin nanoparticles (OMV-PTX-SF-NPs) were prepared by high-pressure co-extrusion, the size and zeta potential of the OMV-PTX-SF-NPs were measured. The antitumor effects of OMV-PTX-SF-NPs were evaluated by cellular and pharmacodynamic assays, and pharmacokinetic experiments were performed. The results showed that hydrophobic forces and hydrogen bonding played a major role in the interaction between paclitaxel and filipin proteins, and the size of OMV-PTX-SF-NPs was 199.8 ± 2.8 nm, zeta potential was -17.8 ± 1.3 mv. The cellular and in vivo pharmacokinetic assays demonstrated that the OMV-PTX-SF-NPs possessed a promising antitumor effect. Pharmacokinetic experiments showed that the AUC0-∞ of OMV-PTX-SF-NPs was 5.314 ± 0.77, which was much larger than that of free PTX, which was 0.744 ± 0.14. Overall, we have successfully constructed a stable oral formulation of paclitaxel with a sustained-release effect, which is able to effectively increase the bioavailability of paclitaxel, improve the antitumor activity, and reduce the adverse effects.

Photoredox-Catalyzed Decarboxylative Bromination, Chlorination and Thiocyanation Using Inorganic Salts.

Decarboxylative halogenation reactions of alkyl carboxylic acids are highly valuable reactions for the synthesis of structurally diverse alkyl halides. However, many reported protocols rely on stoichiometric strong oxidants or highly electrophilic halogenating agents. Herein, we describe visible-light photoredox-catalyzed decarboxylative halogenation reactions of N-hydroxyphthalimide-activated carboxylic acids that avoid stoichiometric oxidants and use inexpensive inorganic halide salts as the halogenating agents. Bromination with lithium bromide proceeds under simple, transition-metal-free conditions using an organic photoredox catalyst and no other additives, whereas dual photoredox-copper catalysis is required for chlorination with lithium chloride. The mild conditions display excellent functional-group tolerance, which is demonstrated through the transformation of a diverse range of structurally complex carboxylic acid containing natural products into the corresponding alkyl bromides and chlorides. In addition, we show the generality of the dual photoredox-copper-catalyzed decarboxylative functionalization with inorganic salts by extension to thiocyanation with potassium thiocyanide, which was applied to the synthesis of complex alkyl thiocyanates.

Self-Assembled L-DNA Linkers for Rapid Construction of Multi-Specific Antibody-Drug Conjugates Library.

One of the key challenges of improving clinical outcomes of antibody drug conjugates (ADCs) is overcoming cancer resistance to the antibody and/or drug components of ADCs, and hence the need for ADC platforms with high combinatory flexibility. Here, we introduce the use of self-assembled left-handed DNA (L-DNA) oligonucleotides to link combinatory single-domain antibodies and toxin payloads for tunable and adaptive delivery of ADCs. We demonstrate that the method allows convenient construction of a library of ADCs with multi-specific targeting, multi-specific payloads, and exact drug-antibody ratio. The newly constructed ADCs with L-DNA scaffold showed favorable properties of in vitro cell cytotoxicity and in vivo suppression and eradication of solid tumors. Collectively, our data suggest that the L-DNA based modular ADC (MADC) platform is a viable option for generating therapeutic ADCs and for potentially expanding ADC therapeutic window via multi-specificity.

Cyclosporine A blocks autophagic flux in tubular epithelial cells by impairing TFEB-mediated lysosomal function.

Cyclosporine A (CsA) is an immunosuppressor widely used for the prevention of acute rejection during solid organ transplantation. However, severe nephrotoxicity has substantially limited its long-term usage. Recently, an impaired autophagy pathway was suggested to be involved in the pathogenesis of chronic CsA nephrotoxicity. However, the underlying mechanisms of CsA-induced autophagy blockade in tubular cells remain unclear. In the present study, we observed that CsA suppressed the activation and expression of transcription factor EB (TFEB) by increasing the activation of mTOR, in turn promoting lysosomal dysfunction and autophagy flux blockade in tubular epithelial cells (TECs) in vivo and in vitro. Restoration of TFEB activation by Torin1-mediated mTOR inhibition significantly improved lysosomal function and rescued autophagy pathway activity, suppressing TEC injury. In summary, targeting TFEB-mediated autophagy flux represents a potential therapeutic strategy for CsA-induced nephrotoxicity.

TGFBR3 is an independent unfavourable prognostic marker in oesophageal squamous cell cancer and is positively correlated with Ki-67.

The transforming growth factor beta (TGF-ß) superfamily plays an important role in cancer development. One aspect of this is that the transforming growth factor beta receptor III (TGFBR3) is frequently overexpressed in some tumours. However, the role of TGFBR3 in oesophageal squamous cell carcinoma (ESCC) has not been explored as yet. In this study, we aimed to determine the role of TGFBR3 in the development and prognosis of ESCC and the correlation between TGFBR3 expression and Ki-67 and p53. Immunohistochemistry was performed to investigate the expression of TGFBR3 in the tumour tissue microarray consisting of ESCC tissues and matched adjacent normal tissues (n = 80). Only ESCC tissues (n = 20) were also used in our analysis. The association between TGFBR3 expression and clinicopathological characteristics, such as Ki-67 and p53, was analysed by Spearman's rank correlation coefficient analysis. The association between TGFBR3 expression and prognosis of ESCC was analysed using Kaplan-Meier analysis and log-rank tests. The expression levels of TGFBR3 in oesophageal cancer tissues were markedly higher than in matched adjacent normal tissues. Furthermore, TGFBR3 overexpression was significantly associated with tumour-node-metastasis (TNM) stage, lymph node metastasis (N stage) and Ki-67 expression. However, TGFBR3 overexpression was not significantly related to age, sex or p53. In univariate analysis, overall survival of ESCC patients was significantly associated with high TGFBR3 expression, sex, T stage, N stage and TNM stage. Moreover, ESCC patients with high TGFBR3 expression had poorer overall survival than those with low TGFB R3 expression. Our findings showed that TGFBR3 was upregulated in the development of human ESCC and high TGFBR3 expression was associated with high expression of Ki-67 and poor prognosis of ESCC. Therefore, TGFBR3 may be a valuable prognostic marker and a novel therapeutic target for ESCC.

Autophagy Inhibition Sensitizes Renal Tubular Epithelial Cell to G1 Arrest Induced by Transforming Growth Factor beta (TGF-ß).

BACKGROUND Cell cycle arrest and autophagy have been demonstrated to be involved in various transforming growth factor (TGF)-ß-mediated phenotype alterations of tubular epithelial cells (TECs) and tubulointerstitial fibrosis. But the relationship between cell cycle arrest and the autophagy induced by TGF-ß has not been explored well. MATERIAL AND METHODS The effects of autophagy inhibition on TGF-ß-induced cell cycle arrest in TECs were explored in vitro. Human kidney-2 (HK-2) cells were stimulated by TGF-ß with or without a combined treatment of autophagy inhibitor chloroquine (CQ) or bafilomycin A1 (Baf). RESULTS Autophagy inhibition by CQ or Baf promotes the suppression of growth in TGF-ß-treated HK-2 cells, as detected by the Cell Counting Kit-8 (CCK-8) method. In addition, CQ or Baf stimulation enhances G1 arrest in TGF-ß treated HK-2 cells, as investigated using propidium iodide (PI) staining and flow cytometry, which was further confirmed by a decrease in the expression of phosphorylated retinoblastoma protein (p-RB) and cyclin-dependent kinase 4 (CDK4). The upregulation of p21 induced by CQ or Baf may mediate an enhanced G1 arrest in TGF-ß treated HK-2 cells. Western blot analysis showed that TGF-ß-induced expression of extracellular matrix fibronectin was notably upregulated in the presence of autophagy inhibitors. CONCLUSIONS Inhibition of autophagy sensitizes the TECs to G1 arrest and proliferation suppression induced by TGF-ß that contributes to the induction of tubulointerstitial fibrosis.

Molecular characterization and immune protection of an AN1-like zinc finger protein of Eimeria tenella.

Coccidiosis is caused by multiple species of the apicomplexan protozoa Eimeria. Among them, Eimeria tenella is frequently considered to be the most pathogenic. Zinc finger proteins (ZnFPs) are a type of protein containing zinc finger domains. In the present study, a putative Eimeria tenella AN1-like ZnFP (E. tenella AN1-like zinc finger domain-containing protein, putative partial mRNA, EtAN1-ZnFP) was cloned and characterized, and its immune protective effects were evaluated. The 798-bp ORF sequence of EtAN1-ZnFP that encoded a protein of approximately 27.0 kDa was obtained. The recombinant EtAN1-ZnFP protein (rEtAN1-ZnFP) was expressed in Escherichia coli. Western blot analysis showed that the recombinant protein was recognized by the anti-GST monoclonal antibody and anti-sporozoite protein rabbit serum. qPCR analysis revealed that EtAN1-ZnFP was highly expressed in unsporulated oocysts and sporozoites. Immunostaining with an anti-rEtAN1-ZnFP antibody indicated that EtAN1-ZnFP was uniformly distributed in the cytoplasm of sporozoites, except for the refractive body; furthermore, this protein was evenly distributed in the cytoplasm of immature schizonts but seldom distributed in mature schizonts. The results of the in vitro invasion inhibition assay indicated that the antibodies against rEtAN1-ZnFP efficiently reduced the ability of E. tenella sporozoites to invade host cells. Animal challenge experiments demonstrated that the chickens immunized with rEtAN1-ZnFP protein significantly decreased mean lesion scores and fecal oocyst output compared with challenged control group. The results suggest that EtAN1-ZnFP can induce partial immune protection against infection with E. tenella and could be an effective candidate for the development of new vaccines.

Molecular characterization of surface antigen 10 of Eimeria tenella.

Chicken coccidiosis is caused by the apicomplexan parasite Eimeria spp. At present, drug resistance of Eimeria is common because of the indiscriminate use of anticoccidial drugs. The gene encoding surface antigen 10 of Eimeria tenella (EtSAG10) is differentially expressed between drug-resistant and drug-sensitive strains. RNA-seq analysis indicated that this gene was downregulated in strains resistant to maduramicin and diclazuril compared to susceptible strains. EtSAG10 DNA sequence alignment revealed that they contained one and ten mutations in MRR and DZR, compared with DS, respectively. A full-length EtSAG10 cDNA was successfully cloned and expressed, and the polyclonal antibody was prepared. The transcription and translation levels of EtSAG10 were analyzed by quantitative real-time PCR (qPCR) and Western blotting. The localization of EtSAG10 in Spz, Mrz, and parasites in the first asexual stage was determined by indirect immunofluorescence. The potential association of EtSAG10 with sporozoite invasion of host cells was assessed by invasion inhibition assays. The results showed that EtSAG10 had a predicted transmembrane domain at the C-terminal end and a predicted signal peptide at the N-terminal end. EtSAG10 was downregulated in drug-resistant strains, which is consistent with the RNA-seq results. The EtSAG10 protein was localized to the parasite surface and parasitophorous vacuole membrane. This protein was shown to play a role in the infection of chicken intestine by sporozoites.

Effects of host fatty acid-binding protein 4 on Eimeria tenella sporozoites invasion of cells.

In our previous study, proteomics analyses of host cells infected with Eimeria tenella sporozoites coupled with isobaric tags for relative and absolute quantitation, identified several host proteins related to Eimeria invasion. In this study, A 458-bp Gallus gallus fatty acid-binding protein 4 (FABP4) gene was cloned and subcloned to pET-28c(+) vector to construct the prokaryotic recombinant expression plasmid pET-28c(+)-FABP4. The 18.5 kDa recombinant FABP4 protein (rFABP4) was expressed and identified by western blotting. Expression of FABP4 in E. tenella sporozoite-infected DF-1 cells was downregulated significantly than in non-infected cells detected by western blotting and immunohistochemistry. The antibody inhibition assay showed that antibodies against FABP4 at 50, 100, 200, 300, and 400 µg/mL had no significant effect on sporozoite invasion. BMS-309403 and transforming growth factor-ß3 (TGF-ß3) was used to inhibit and improve the expression of FABP4 in DF-1 cells, respectively, and their effect on the sporozoite invasion of cells was detected by flow cytometry. Sporozoite invasion rate in the BMS-309403-treated group was not significantly affected; however, the invasion rate in the TGF-ß3-treated group declined significantly. These results show that host FABP4 plays a negative role in Eimeria invasion. However, further studies are needed to elucidate the exact mechanism of how FABP4 negatively regulates Eimeria invasion.

Accelerated Glomerular Cell Senescence in Experimental Lupus Nephritis.

BACKGROUND The aim of this study was to determine whether senescence in renal glomeruli is involved in lupus nephritis (LN); the expression of senescence-associated ß-galactosidase (SA-ß-Gal) and its association with glomerular lesions were investigated in a mouse model of LN. MATERIAL AND METHODS Eighteen MRL/lpr mice with severe proteinuria were randomly divided into 2 equal groups and intraperitoneally injected with dexamethasone (DEX) or saline; 4 age-matched mice with mild proteinuria served as controls. Serum creatinine and urinary protein levels were analyzed, and kidney histological changes were observed by periodic acid-Schiff and Sirius Red staining. SA-ß-Gal was detected via histochemistry. Glomerular expression of collagen IV, α-SMA, and nephrin was analyzed by immunohistochemistry, and glomerular complement C3 deposition was tested by immunofluorescence. The relationships between SA-ß-Gal expression and renal function or glomerular lesion markers were determined by Spearman's correlation analysis. RESULTS Mice with severe proteinuria exhibited glomerular segmental sclerosis and endothelial cell proliferation. DEX administration suppressed these lesions but had no significant effect on 24-hour urinary protein levels. The elevated glomerular expression of SA-ß-Gal in proteinuric mice was attenuated by DEX treatment. In addition, DEX treatment markedly downregulated glomerular C3 deposition and collagen IV and α-SMA expression, while significantly increasing nephrin expression. Furthermore, SA-ß-Gal expression was positively correlated with urinary protein levels and expression of α-SMA. CONCLUSIONS Accelerated senescence of glomerular cells may contribute to glomerular injury in LN.

Risk of atrial fibrillation in patients with multiple myeloma: what is known and directions for future study.

BACKGROUND: Multiple myeloma (MM) is a prevalent hematological tumor, and recent clinical data have highlighted the significance of atrial fibrillation (AF) as a crucial complication affecting the prognosis of MM. This review aims to consolidate findings from published clinical studies, focusing on the epidemiological characteristics of AF in MM patients and the associated risks arising from MM treatments such as autologous hematopoietic stem cell transplantation, proteasome inhibitors, and immunomodulatory agents. MAIN BODY: While existing data partially demonstrate a strong correlation between MM and AF, further clinical studies are necessary to comprehensively investigate their association. These studies should encompass various aspects, including the risk of AF resulting from MM treatment, the impact of AF-induced embolic events and heart failure on MM prognosis, as well as the influence of AF management methods like catheter ablation or left atrial appendage closure on MM prognosis. CONCLUSIONS: The supplementation of future data will provide more precise guidance for managing MM patients. By incorporating information regarding AF risk associated with MM treatment and examining the effects of AF management strategies on MM prognosis, healthcare professionals can enhance their decision-making process when caring for individuals with MM.

Severe hypoxemia after radiofrequency ablation for atrial fibrillation in palliatively repaired tetralogy of Fallot: A case report.

BACKGROUND: Patients with tetralogy of Fallot (TOF) often have arrhythmias, commonly being atrial fibrillation (AF). Radiofrequency ablation is an effective treatment for AF and does not usually cause severe postoperative hypoxemia, but the risk of complications may increase in patients with conditions such as TOF. CASE SUMMARY: We report a young male patient with a history of TOF repair who developed severe hypoxemia after radiofrequency ablation for AF and was ultimately confirmed to have a new right-to-left shunt. The patient subsequently underwent atrial septal occlusion and eventually recovered. CONCLUSION: Radiofrequency ablation may cause iatrogenic atrial septal injury; thus possible complications should be predicted in order to ensure successful treatment and patient safety.

Overcoming neutrophil-induced immunosuppression in postoperative cancer therapy: Combined sialic acid-modified liposomes with scaffold-based vaccines.

Immunotherapy is a promising approach for preventing postoperative tumor recurrence and metastasis. However, inflammatory neutrophils, recruited to the postoperative tumor site, have been shown to exacerbate tumor regeneration and limit the efficacy of cancer vaccines. Consequently, addressing postoperative immunosuppression caused by neutrophils is crucial for improving treatment outcomes. This study presents a combined chemoimmunotherapeutic strategy that employs a biocompatible macroporous scaffold-based cancer vaccine (S-CV) and a sialic acid (SA)-modified, doxorubicin (DOX)-loaded liposomal platform (DOX@SAL). The S-CV contains whole tumor lysates as antigens and imiquimod (R837, Toll-like receptor 7 activator)-loaded PLGA nanoparticles as immune adjuvants for cancer, which enhance dendritic cell activation and cytotoxic T cell proliferation upon localized implantation. When administered intravenously, DOX@SAL specifically targets and delivers drugs to activated neutrophils in vivo, mitigating neutrophil infiltration and suppressing postoperative inflammatory responses. In vivo and vitro experiments have demonstrated that S-CV plus DOX@SAL, a combined chemo-immunotherapeutic strategy, has a remarkable potential to inhibit postoperative local tumor recurrence and distant tumor progression, with minimal systemic toxicity, providing a new concept for postoperative treatment of tumors.

Repolarizing Tumor-Associated Macrophages and inducing immunogenic cell Death: A targeted liposomal strategy to boost cancer immunotherapy.

Cancer immunotherapy has shown promise in treating various malignancies. However, the presence of an immunosuppressive tumor microenvironment (TME) triggered by M2 tumor-associated macrophages (TAMs) and the limited tumor cell antigenicity have hindered its broader application. To address these challenges, we developed DOX/R837@ManL, a liposome loaded with imiquimod (R837) and doxorubicin (DOX), modified with mannose-polyethylene glycol (Man-PEG). DOX/R837@ManL employed a mannose receptor (MRC1)-mediated targeting strategy, allowing it to accumulate selectively at M2 Tumor associated macrophages (TAMs) and tumor sites. R837, an immune adjuvant, promoted the conversion of immunosuppressive M2 TAMs into immunostimulatory M1 TAMs, and reshaped the immunosuppressive TME. Simultaneously, DOX release induced immunogenic cell death (ICD) in tumor cells and enhanced tumor cell antigenicity by promoting dendritic cells (DCs) maturation. Through targeted delivery, the synergistic action of R837 and DOX activated innate immunity and coordinated adaptive immunity, enhancing immunotherapy efficacy. In vivo experiments have demonstrated that DOX/R837@ManL effectively eliminated primary tumors and lung metastases, while also preventing tumor recurrence post-surgery. These findings highlighted the potential of DOX/R837@ManL as a promising strategy for cancer immunotherapy.

Deep Reinforcement Learning on Autonomous Driving Policy With Auxiliary Critic Network.

Deep reinforcement learning (DRL) is a machine learning method based on rewards, which can be extended to solve some complex and realistic decision-making problems. Autonomous driving needs to deal with a variety of complex and changeable traffic scenarios, so the application of DRL in autonomous driving presents a broad application prospect. In this article, an end-to-end autonomous driving policy learning method based on DRL is proposed. On the basis of proximal policy optimization (PPO), we combine a curiosity-driven method called recurrent neural network (RNN) to generate an intrinsic reward signal to encounter the agent to explore its environment, which improves the efficiency of exploration. We introduce an auxiliary critic network on the original actor-critic framework and choose the lower estimate which is predicted by the dual critic network when the network update to avoid the overestimation bias. We test our method on the lane- keeping task and overtaking task in the open racing car simulator (TORCS) driving simulator and compare with other DRL methods, experimental results show that our proposed method can improve the training efficiency and control performance in driving tasks.

Association between circulating leukocytes and arrhythmias: Mendelian randomization analysis in immuno-cardiac electrophysiology.

Background: Cardiac arrhythmia is a common disease associated with high mortality and morbidity. Circulating leukocyte counts, which serve as a biomarker for assessing systemic immune status, have been linked to arrhythmias in observational studies. However, observational studies are plagued by confounding factors and reverse causality, whether alterations in circulating leukocyte components are causally associated with arrhythmias remains uncertain. The present study explored this question based on genetic evidence. Methods and findings: We performed Mendelian randomization (MR) analysis to evaluate whether alterations in leukocyte counts affect aggregated risk of all types of arrhythmia or risk of five specific types of arrhythmia. Single-nucleotide polymorphisms serving as proxies for leukocyte differential counts were retrieved from the Blood Cell Consortium, and statistical data on arrhythmias were obtained from the UK Biobank), FinnGenand a meta-analysis of genome-wide association studies for atrial fibrillation. We applied inverse variance-weighted method as the primary analysis, complemented by a series of sensitivity analyses. Bidirectional analyses were conducted to assess reverse causality. Finally, multivariable MR was performed to study the joint effects of multiple risk factors. We found that genetically predicted differential leukocyte counts were not significantly associated with aggregated occurrence of all types of arrhythmia. In contrast, each 1-standard deviation increase in lymphocyte count was associated with 46% higher risk of atrioventricular block (OR 1.46, 95% CI 1.11-1.93, p=0.0065). A similar effect size was observed across all MR sensitivity analyses, with no evidence of horizontal pleiotropy. Reverse MR analysis suggested that atrioventricular block was unlikely to cause changes in lymphocyte count. Primary MR analysis based on the inverse-variance weighted method suggested that changes in neutrophil count alter risk of right bundle branch block, and changes in basophil count alter risk of atrial fibrillation. However, these causal relationships were not robust in sensitivity analyses. We found no compelling evidence that neutrophil or lymphocyte counts cause atrial fibrillation. Conclusion: Our data support higher lymphocyte count as a causal risk factor for atrioventricular block. These results highlight the importance of immune cells in the pathogenesis of specific cardiac conduction disorders.

Pore Evolution in Refractory Gold Ore Formed by Oxidation Roasting and the Effect on the Cyanide Leaching Process.

Refractory gold ore is usually affected by the associated carbonaceous matter through the preg-robbing effect, which is eliminated by oxidation roasting, followed by leaching, to achieve a satisfactory gold leaching efficiency. Roasting-leaching experiments, pore structure measurements, scanning electron microscopy (SEM), and X-ray diffraction are used to explore the structural evolution of pores on the surface and its effect on the leaching performance. Pores with optimal sizes were obtained by roasting at 650 °C for 2.0 h with a ventilation of 0.6 m3/h; approximately 92.55% gold could be recovered under these conditions. A porous structure observed by SEM became more compact as the temperature further increased to 850 °C. The formation of CaSiO3 and CaSO4 in pores led to pore shrinkage. The mechanism of oxidation roasting, followed by cyanide leaching, was schematically analyzed and revealed the effects of pore structural evolution and phase transformation on the leaching efficiency.

Rice starch multi-level structure and functional relationships.

Starch from 15 different rice genotypes with amylose content (AC) ranging 1.5%-30.6% were investigated for relationships between structures and properties. For parameters related to the granular level, the most important relationships were found for AC, average chain lengths (ACL) of the amylopectin (AP) fb1 chains having a length of DP 13-24, crystallinity, and the thickness of the crystalline (dc) and the amorphous lamellae (da) of the starch granule. AC and dc were negatively correlated with the peak gelatinization temperature (Tp), thermal enthalpy (ΔH), and peak viscosity (PV), but positively correlated with swelling power. ACLfb1 and da, as compared to AC and dc, had the opposite effects on these parameters, demonstrating important roles of specific molecular and lamellar structures on the starch granular stability. For the gelatinized systems, increasing ACLfb1 decreased retrogradation, while AC increased retrogradation by increasing the resistant starch (RS) content, storage modulus (G'), and setback (SB).

The Role of Parietal Epithelial Cells in the Pathogenesis of Podocytopathy.

Podocytopathy is the most common feature of glomerular disorder characterized by podocyte injury- or dysfunction-induced excessive proteinuria, which ultimately develops into glomerulosclerosis and results in persistent loss of renal function. Due to the lack of self-renewal ability of podocytes, mild podocyte depletion triggers replacement and repair processes mostly driven by stem cells or resident parietal epithelial cells (PECs). In contrast, when podocyte recovery fails, activated PECs contribute to the establishment of glomerular lesions. Increasing evidence suggests that PECs, more than just bystanders, have a crucial role in various podocytopathies, including minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, diabetic nephropathy, IgA nephropathy, and lupus podocytopathy. In this review, we attempt to dissect the diverse role of PECs in the pathogenesis of podocytopathy based on currently available information.

The kidney-expressed transcription factor ZKSCAN3 is dispensable for autophagy transcriptional regulation and AKI progression in mouse.

Acute kidney injury (AKI) is a common clinical disease that can cause serious harm to the kidneys, but it has no effective treatment till now. The modulation of autophagy pathway regulation is considered a potentially effective therapeutic approach in AKI prevention and treatment. ZKSCAN3 has been shown to be an important transcription factor that negatively regulates autophagy activity in cancer tissues. In order to determine whether autophagy could be activated by knocking out ZKSCAN3 to exert the renal protective effect of autophagy, we constructed AKI models with Zkscan3 knockout (KO) mice and detected renal pathological changes and renal function changes as well as autophagy-related indicators. We found that Zkscan3 KO had no significant effect on kidney development. Besides, no significant changes in autophagy activity were observed under normal physiological or AKI conditions. In non-tumor tissues, ZKSCAN3 did not mediate transcriptional regulation of autophagy-related genes. These findings suggest that because ZKSCAN3 may not function in the transcriptional regulation of autophagy-related genes in non-tumor tissues, it may not be used as a therapeutic target for AKI.