Publications by authors named "Xindi Zhou"

The formation of immune synapses (ISs) between cytotoxic T cells and tumor cells is crucial for effective tumor elimination. However, the role of ISs in immune evasion and resistance to immune checkpoint blockades (ICBs) remains unclear. We demonstrate that ICAM-1, a key IS molecule activating LFA-1 signaling in T and natural killer (NK) cells, is often expressed at low levels in cancers.

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Purpose: This study identified factors that identification of progression-predicting utility from steroid-sensitive nephrotic syndrome(SSNS) to steroid-dependent or frequently relapsing nephrotic syndrome (SDNS/FRNS) in patients and developed a corresponding predictive model.

Patients And Methods: This retrospective study analyzed clinical data from 756 patients aged 1 to 18 years, diagnosed with SSNS, who received treatment at the Department of Nephrology, Children's Hospital of Chongqing Medical University, between November 2007 and May 2023. We developed a shrinkage and selection operator (LASSO) - logistic regression model, which was visualized using a nomogram.

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Optineurin (OPTN), a multifunctional adaptor protein in mammals, plays critical roles in many cellular processes, such as vesicular trafficking and autophagy. Notably, mutations in optineurin are directly associated with many human diseases, such as amyotrophic lateral sclerosis (ALS). OPTN can specifically recognize Rab8a and the GTPase-activating protein TBC1D17, and facilitate the inactivation of Rab8a mediated by TBC1D17, but with poorly understood mechanism.

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The glomerular basement membrane (GBM) is a critical component of the glomerular filtration barrier (GFB), with its thickness directly influencing renal function. While a uniformly thinned GBM can cause hematuria while preserving normal renal function, this condition is typically diagnosed as thin basement membrane nephropathy (TBMN). However, the pathogenesis and potential progression to renal insufficiency of TBMN are not fully understood.

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Article Synopsis
  • * The study reveals how STBD1 interacts with glycogen and ATG8 proteins, detailing its unique binding sites and the importance of a specific motif (LIR) for these interactions.
  • * The findings also show that STBD1 recruits RB1CC1, a crucial factor for starting autophagy, further clarifying how STBD1 facilitates glycophagy through several molecular interactions.
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  • Disruptions in gene expression related to the glomerular basement membrane (GBM) could lead to kidney problems in children, yet understanding the GBM's role in pediatric kidney diseases requires more research.
  • The study focused on key GBM components like Collagen IV, Laminin, and Integrin across common pediatric kidney diseases, revealing specific changes in their expression.
  • Findings showed increased expression of certain proteins in idiopathic nephrotic syndrome (INS), while reduced levels were noted in other conditions like IgA nephropathy and lupus nephritis, indicating structural changes in the GBM common to various childhood kidney diseases.
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  • TAX1BP1 is an important adaptor in autophagy that interacts with several proteins to facilitate selective autophagy for specific substrates.
  • The study reveals two distinct binding sites for TAX1BP1 with RB1CC1 and describes a newly discovered coiled-coil interaction, along with the crystal structure of their complex.
  • Findings also show that RB1CC1 and NAP1 compete for binding to TAX1BP1 and that a specific motif from NAP1 enhances the stability of their combined complex, while a unique binding mechanism with ATG8 family proteins is also characterized.
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HOIL-1L and SHARPIN are two essential regulatory subunits of the linear ubiquitin chain assembly complex (LUBAC), which is the only known E3 ligase complex generating linear ubiquitin chains. In addition to their LUBAC-dependent functions, HOIL-1L and SHARPIN alone play crucial roles in many LUBAC-independent cellular processes. Importantly, deficiency of HOIL-1L or SHARPIN leads to severe disorders in humans or mice.

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Objective: Diabetic kidney disease (DKD) is characterized by the abnormal deposition of oxidized low-density lipoprotein (ox-LDL), which contributes to podocyte damage. Klotho, an aging suppressor that plays a critical role in protecting podocytes in DKD, is mainly expressed in kidney tubular epithelium and secreted in the blood. However, it has not been established whether Klotho can alleviate podocyte injury by inhibiting renal ox-LDL deposition, and the potential molecular mechanisms require further investigation.

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Heme-oxidized IRP2 ubiquitin ligase 1 (HOIL-1L) serves as a unique E3 ligase to catalyze the mono-ubiquitination of relevant protein or sugar substrates and plays vital roles in numerous cellular processes in mammals. However, the molecular mechanism underpinning the E3 activity of HOIL-1L and the related regulatory mechanism remain elusive. Here, we report the crystal structure of the catalytic core region of HOIL-1L and unveil the key catalytic triad residues of HOIL-1L.

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The glomerular basement membrane (GBM) consists of laminins, collagen IV, nidogens, and fibronectin and is essential for filtration barrier integrity in the kidney. Critically, structural and functional abnormalities in the GBM are involved in chronic kidney disease (CKD) occurrence and development. Fibronectin is encoded by FN1 and is essential for podocyte-podocyte and podocyte-matrix interactions.

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Background: Proteinuria is an unfavorable clinical condition highly associated with a risk of renal and cardiovascular disease in chronic kidney disease (CKD). However, whether all proteinuria forms are linked to renal impairment are still unclear. Cubilin is an endocytic receptor highly expressed in renal proximal tubules mediating uptake of albumin, transferrin and α1-microglobulin.

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TRPC6 and TRPC3 are receptor-activated nonselective cation channels that belong to the family of canonical transient receptor potential (TRPC) channels. They are activated by diacylglycerol, a lipid second messenger. TRPC6 and TRPC3 are involved in many physiological processes and implicated in human genetic diseases.

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Intense inflammatory pain caused by urate crystals in joints and other tissues is a major symptom of gout. Among therapy drugs that lower urate, benzbromarone (BBR), an inhibitor of urate transporters, is widely used because it is well tolerated and highly effective. We demonstrate that BBR is also an activator of voltage-gated KCNQ potassium channels.

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