\documentclass[10pt]{article}

\usepackage{fullpage}
\usepackage{setspace}
\usepackage{parskip}
\usepackage{titlesec}
\usepackage[section]{placeins}
\usepackage{xcolor}
\usepackage{breakcites}
\usepackage{lineno}
\usepackage{hyphenat}





\PassOptionsToPackage{hyphens}{url}
\usepackage[colorlinks = true,
            linkcolor = blue,
            urlcolor  = blue,
            citecolor = blue,
            anchorcolor = blue]{hyperref}
\usepackage{etoolbox}
\makeatletter
\patchcmd\@combinedblfloats{\box\@outputbox}{\unvbox\@outputbox}{}{%
  \errmessage{\noexpand\@combinedblfloats could not be patched}%
}%
\makeatother


\usepackage{natbib}




\renewenvironment{abstract}
  {{\bfseries\noindent{\abstractname}\par\nobreak}\footnotesize}
  {\bigskip}

\titlespacing{\section}{0pt}{*3}{*1}
\titlespacing{\subsection}{0pt}{*2}{*0.5}
\titlespacing{\subsubsection}{0pt}{*1.5}{0pt}


\usepackage{authblk}


\usepackage{graphicx}
\usepackage[space]{grffile}
\usepackage{latexsym}
\usepackage{textcomp}
\usepackage{longtable}
\usepackage{tabulary}
\usepackage{booktabs,array,multirow}
\usepackage{amsfonts,amsmath,amssymb}
\providecommand\citet{\cite}
\providecommand\citep{\cite}
\providecommand\citealt{\cite}
% You can conditionalize code for latexml or normal latex using this.
\newif\iflatexml\latexmlfalse
\providecommand{\tightlist}{\setlength{\itemsep}{0pt}\setlength{\parskip}{0pt}}%

\AtBeginDocument{\DeclareGraphicsExtensions{.pdf,.PDF,.eps,.EPS,.png,.PNG,.tif,.TIF,.jpg,.JPG,.jpeg,.JPEG}}

\usepackage[utf8]{inputenc}
\usepackage[greek,english]{babel}



\usepackage{float}








\begin{document}

\title{Farrerol ameliorated renal fibrosis mediated by mitophagy deficiency in
cisplatin-induced chronic kidney disease via Nrf2/PINK1}



\author[1]{Ning Ma}%
\author[1]{Jianqiang HU}%
\author[1]{Wenjing  Gu}%
\author[1]{Xinxin Ci}%
\affil[1]{Jilin University First Hospital}%


\vspace{-1em}



  
  \date{May 17, 2024}


\begingroup
\let\center\flushleft
\let\endcenter\endflushleft
\maketitle
\endgroup





\selectlanguage{english}
\begin{abstract}
Background and Purpose: Mitochondrial dysfunction is essential in renal
tubular damage, and mitophagy, a selective form of autophagy,
specifically eliminates damaged mitochondria. Mitophagy reportedly
protects against diabetic kidney disease, cisplatin-induced acute kidney
injury (AKI) and other related kidney diseases, but the specific
mechanism by which mitophagy protects against cisplatin-induced chronic
kidney disease (CKD) remains unclear. Experimental Approach: The effects
of farrerol on cisplatin-induced AKI in mice were investigated. C57BL/6
wild-type and Nrf2 knockout mice were used to evaluate the protective
effect of farrerol on cisplatin-induced CKD. Key Results: we confirmed
that Nrf2- and PINK1/Parkin-mediated mitophagy was significantly
increased on the 3rd day of cisplatin stimulation but was reduced on the
38th day of cisplatin stimulation. Similar to previous results,
farrerol, a natural compound, also activated Nrf2 on the 38th day of
cisplatin administration, subsequently stimulating the Nrf2-targeted
antioxidant enzymes HO-1 and NQO1. In addition, farrerol triggered
PINK1/Parkin-mediated mitophagy by recruiting the receptor proteins LC3
and p62/SQSTM1, thereby eliminating damaged mitochondria. Furthermore,
genetic deletion of Nrf2 reduced PINK1/Parkin-mediated mitophagy
activation and led to increased renal tubular necrosis and renal
fibrosis. We also found that farrerol alleviated inflammation and renal
fibrosis by inhibiting p-NF-\selectlanguage{greek}κ\selectlanguage{english}B/NLRP3 and TGF-\selectlanguage{greek}β/\selectlanguage{english}Smad signaling.
Conclusions: These data indicated that farrerol effectively inhibited
cisplatin-induced inflammation and renal fibrosis by activating Nrf2 and
PINK1/Parkin-mediated mitophagy, which provides a potential novel
therapeutic target for CKD.%
\end{abstract}%



\sloppy


\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure1/Figure1}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure2/Figure2}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure3/Figure3}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure4/Figure4}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure5/Figure5}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure6/Figure6}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure7/Figure7}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure8/Figure8}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure9/Figure9}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/--Data-Availability-Statement-Instructions/--Data-Availability-Statement-Instructions}

\end{center}
\end{figure}

\selectlanguage{english}
\FloatBarrier
\end{document}

