\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[english]{babel}



\usepackage{float}








\begin{document}

\title{Mesenchymal Stem Cells Regulate Microglial Polarization via Inhibition
of the HMGB1/TLR4 Signaling Pathway in Diabetic Retinopathy}



\author[1]{Jun Tong}%
\author[1]{Genhong Yao}%
\author[1]{Yueqin Chen}%
\author[1]{Hairong Xie}%
\author[1]{Xinyu Zheng}%
\author[1]{Lingyun Sun}%
\author[2]{Zhenping Huang}%
\author[1]{Zhenggao Xie}%
\affil[1]{Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital}%
\affil[2]{East Region Military Command General Hospital}%


\vspace{-1em}



  
  \date{June 08, 2024}


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





\selectlanguage{english}
\begin{abstract}
Diabetic retinopathy (DR) is recognized as the most prevalent retinal
degenerative disorder. Inflammatory response particularly precedes
microvascular alteration, considered the primary factor of diabetic
retinopathy. Actived microglia express many pro-inflammatory cytokines
exacerbates retina inflammation and disruption. In the present study, we
investigated that MSCs alleviated blood--retina barrier (BRB) breakdown
in diabetic rats, as evidenced by reduced retinal edema, decreased
vascular leakage, and increased occludin expression. The MSCs-treated
retinal microglia in the diabetic rats exhibited reduced expression of
M1-phenotype markers, including inducible nitric oxide synthase (iNOS),
CD16, and pro-inflammatory cytokines. Meanwhile, MSCs increased the
expression of M2-phenotype markers, such as arginase-1 (Arg-1), CD206,
and anti-inflammatory cytokines. HMGB1/TLR4 signaling pathway is
activated in DR and inhibited after MSCs treatment. Consistent with in
vivo evidence, MSCs drove BV2 microglia toward M2 phenotype in vitro.
Knocking down HMGB1 or TLR4 in microglia had comparable effects as with
MSCs treatment, suggesting HMGB1/TLR4 pathway is necessary for MSCs'
regulatory effects on microglia polarization. Collectively, MSCs exert a
beneficial effect on DR by polarizing microglia from M1 toward M2
phenotype via inhibiting the HMGB1/TLR4 signaling pathway.%
\end{abstract}%



\sloppy


\textbf{Hosted file}

\verb`IMMNOLOGY.doc`  available at \url{https://authorea.com/users/725384/articles/708636-mesenchymal-stem-cells-regulate-microglial-polarization-via-inhibition-of-the-hmgb1-tlr4-signaling-pathway-in-diabetic-retinopathy}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Fig/Fig}

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

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

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

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-5/Figure-5}

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

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

\end{center}
\end{figure}

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

