The role of sulfur cycle in new particle formation: Cycloaddition reaction of SO3 to H2S.

The chemistry of sulfur cycle contributes significantly to the atmospheric nucleation process, which is the first step of new particle formation (NPF). In the present study, cycloaddition reaction mechanism of sulfur trioxide (SO3) to hydrogen sulfide (H2S) which is a typical air pollutant and toxic gas detrimental to the environment were comprehensively investigate through theoretical calculations and Atmospheric Cluster Dynamic Code simulations. Gas-phase stability and nucleation potential of the product thiosulfuric acid (H2S2O3, TSA) were further analyzed to evaluate its atmospheric impact. Without any catalysts, the H2S + SO3 reaction is infeasible with a barrier of 24.2 kcal/mol. Atmospheric nucleation precursors formic acid (FA), sulfuric acid (SA), and water (H2O) could effectively lower the reaction barriers as catalysts, even to a barrierless reaction with the efficiency of cis-SA > trans-FA > trans-SA > H2O. Subsequently, the gas-phase stability of TSA was investigated. A hydrolysis reaction barrier of up to 61.4 kcal/mol alone with an endothermic isomerization reaction barrier of 5.1 kcal/mol under the catalytic effect of SA demonstrates the sufficient stability of TSA. Furthermore, topological and kinetic analysis were conducted to determine the nucleation potential of TSA. Atmospheric clusters formed by TSA and atmospheric nucleation precursors (SA, ammonia NH3, and dimethylamine DMA) were thermodynamically stable. Moreover, the gradually decreasing evaporation coefficients for TSA-base clusters, particularly for TSA-DMA, suggests that TSA may participate in NPF where the concentration of base molecules are relatively higher. The present new reaction mechanism may contributes to a better understanding of atmospheric sulfur cycle and NPF.

Novel heterozygous mutation of CACNA2D1 gene in a Chinese family with arrhythmia.

BACKGROUND: Primary electrical disorders (PEDs) are a group of cardiac rhythm abnormalities that occur in the absence of detectable structural heart disease and are a significant cause of sudden cardiac death (SCD). The initiation of cardiac muscle contraction and relaxation is orchestrated by the action potential (AP), generated through ionic changes across the membrane. Mutations in the AP-related gene CACNA2D1 have been identified as a causative factor for PED. METHODS: We recruited a Chinese family with a history of arrhythmia. The proband has experienced palpitations and chest tightness for over 40 years, with symptoms worsening over the past year. Whole exome sequencing (WES) was used to determine the genetic etiologies in this family. RESULTS: A novel heterozygous missense mutation (NM_000722.3: c.1685G > C;p.G562A) of CACNA2D1 gene was detected. Genotyping of the proband's parents indicated that the arrhythmia phenotype in the proband was caused by a de novo mutation. CONCLUSIONS: WES was utilized to explore the genetic etiology in a family with arrhythmia, leading to the identification of a novel mutation in the CACNA2D1 gene. This study not only expands the mutation spectrum of the CACNA2D1 gene but also contributes to genetic counseling and clinical diagnosis for this family.

A novel variant (p.A524P) in Spastin is responsible for a Chinese family with hereditary spastic paraplegia.

BACKGROUND: Hereditary spastic paraplegia (HSP) represents a group of monogenic neurodegenerative disorders characterized by high clinical and genetic heterogeneity. HSP is characterized by slowly progressing hypertonia of both lower extremities, spastic gait, and myasthenia. The most prevalent autosomal dominant form of HSP, known as spastic paraplegia 4 (SPG4), is attributed to variants in the spastin (SPAST) gene. METHODS AND RESULTS: Here, a Chinese family presenting with spasticity in both legs and a shuffling gait participated in our investigation. Whole exome sequencing of the proband was utilized to identify the genetic lesion in the family. Through data filtering, Sanger sequencing validation, and co-separation analysis, a novel variant (NM_014946.3: c.1669G > C:p.A557P) of SPAST was identified as the genetic lesion of this family. Furthermore, bioinformatic analysis revealed that this variant was deleterious and located in a highly evolutionarily conserved site. CONCLUSION: Our study confirmed the diagnosis of SPG4 in this family, contributing to genetic counseling for families affected by SPG4. Additionally, our study broadened the spectrum of SPAST variants and highlighted the importance of ATPases associated with various cellular activity domains of SPAST.

ZCCHC8 p.P410A disrupts nucleocytoplasmic localization, promoting idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a special kind of chronic interstitial lung disease with insidious onset. Previous studies have revealed that mutations in ZCCHC8 may lead to IPF. The aim of this study is to explore the ZCCHC8 mutations in Chinese IPF patients. METHODS: Here, we enrolled 124 patients with interstitial lung disease from 2017 to 2023 in our hospital. Whole exome sequencing and Sanger sequencing were employed to explore the genetic lesions of these patients. RESULTS: Among these 124 patients, a novel mutation (NM_017612: c.1228 C > G/p.P410A) of Zinc Finger CCHC-Type Containing 8 (ZCCHC8)was identified in a family with IPF and chronic obstructive lung disease. As a component of the nuclear exosome-targeting complex that regulates the turnover of human telomerase RNA, ZCCHC8 mutations have been reported may lead to IPF in European population and American population. Functional study confirmed that the novel mutation can disrupt the nucleocytoplasmic localization of ZCCHC8, which further decreased the expression of DKC1 and RTEL1, and finally reduced the length of telomere and led to IPF and related disorders. CONCLUSIONS: We may first report the ZCCHC8 mutation in Asian population with IPF. Our study broadens the mutation, phenotype, and population spectrum of ZCCHC8 deficiency.

Elevated expression of ECT2 as a diagnostic marker and prognostic indicator in endometrial cancer.

OBJECTIVES: The study aims to investigate genes associated with endometrial cancer (EC) progression to identify new biomarkers for early detection. METHODS: Differentially expressed genes (DEGs), Series test of cluster (STC) and protein-protein interaction analyses identified hub genes in EC. Clinical samples were utilized to examine the expression pattern of ECT2, assess its prognostic value, and evaluate its diagnostic potential. RESULTS: Upregulated DEGs were significantly enriched in cancer-related processes and pathways. Validations across databases identified ASPM, ATAD2, BUB1B, ECT2, KIF14, NUF2, NCAPG, and SPAG5 as potential hub genes, with ECT2 exhibiting the highest diagnostic efficacy. The expression levels of ECT2 varied significantly across different clinical stages, pathological grades, and metastasis statuses in UCEC. Furthermore, ECT2 mRNA was upregulated in the p53abn group, indicating a poorer prognosis, and downregulated in the MMRd and NSMP groups, suggesting a moderate prognosis. In clinical samples, ECT2 expression increased from normal endometria and endometrial hyperplasia without atypia (EH) to atypical endometrial hyperplasia (AH) and EC, effectively distinguishing between benign and malignant endometria. High ECT2 expression was associated with an unfavourable prognosis. CONCLUSIONS: ECT2 expression significantly rises in AH and EC, showing high accuracy in distinguishing between benign and malignant endometria. ECT2 emerges as a promising biomarker for diagnosing endometrial neoplasia and as a prognostic indicator in EC.

LDHA contributes to nicotine induced cardiac fibrosis through autophagy flux impairment.

Cardiac fibrosis is a typical feature of cardiac pathological remodeling, which is associated with adverse clinical outcomes and has no effective therapy. Nicotine is an important risk factor for cardiac fibrosis, yet its underlying molecular mechanism remains poorly understood. This study aimed to identify its potential molecular mechanism in nicotine-induced cardiac fibrosis. Our results showed nicotine exposure led to the proliferation and transformation of cardiac fibroblasts (CFs) into myofibroblasts (MFs) by impairing autophagy flux. Through the use of drug affinity responsive target stability (DARTS) assay, cellular thermal shift assay (CETSA), and surface plasmon resonance (SPR) technology, it was discovered that nicotine directly increased the stability and protein levels of lactate dehydrogenase A (LDHA) by binding to it. Nicotine treatment impaired autophagy flux by regulating the AMPK/mTOR signaling pathway, impeding the nuclear translocation of transcription factor EB (TFEB), and reducing the activity of cathepsin B (CTSB). In vivo, nicotine treatment exacerbated cardiac fibrosis induced in spontaneously hypertensive rats (SHR) and worsened cardiac function. Interestingly, the absence of LDHA reversed these effects both in vitro and in vivo. Our study identified LDHA as a novel nicotine-binding protein that plays a crucial role in mediating cardiac fibrosis by blocking autophagy flux. The findings suggest that LDHA could potentially serve as a promising target for the treatment of cardiac fibrosis.

Single-cell transcriptomic profiling reveals decreased ER protein Reticulon3 drives the progression of renal fibrosis.

Chronic kidney disease (CKD) poses a significant global health dilemma, emerging from complex causes. Although our prior research has indicated that a deficiency in Reticulon-3 (RTN3) accelerates renal disease progression, a thorough examination of RTN3 on kidney function and pathology remains underexplored. To address this critical need, we generated Rtn3-null mice to study the consequences of RTN3 protein deficiency on CKD. Single-cell transcriptomic analyses were performed on 47,885 cells from the renal cortex of both healthy and Rtn3-null mice, enabling us to compare spatial architectures and expression profiles across 14 distinct cell types. Our analysis revealed that RTN3 deficiency leads to significant alterations in the spatial organization and gene expression profiles of renal cells, reflecting CKD pathology. Specifically, RTN3 deficiency was associated with Lars2 overexpression, which in turn caused mitochondrial dysfunction and increased reactive oxygen species levels. This shift induced a transition in renal epithelial cells from a functional state to a fibrogenic state, thus promoting renal fibrosis. Additionally, RTN3 deficiency was found to drive the endothelial-to-mesenchymal transition process and disrupt cell-cell communication, further exacerbating renal fibrosis. Immunohistochemistry and Western-Blot techniques were used to validate these observations, reinforcing the critical role of RTN3 in CKD pathogenesis. The deficiency of RTN3 protein in CKD leads to profound changes in cellular architecture and molecular profiles. Our work seeks to elevate the understanding of RTN3's role in CKD's narrative and position it as a promising therapeutic contender.

A de novo Mutation (p.Gln277X) of Cyclin D2 is Responsible for a Child with Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome.

Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome (MPPH), a type of overgrowth syndrome, is characterized by progressive megalencephaly, cortical brain malformations, and distal limb anomalies. Previous studies have revealed that the overactivity of the phosphatidylinositol 3-kinase-Protein kinase B pathway and the increased cyclin D2 (CCND2) expression were the main factors contributing to this disease. Here, we present the case of a patient who exhibited megalencephaly, polymicrogyria, abnormal neuronal migration, and developmental delay. Serum tandem mass spectrometry and chromosome examination did not detect any metabolic abnormalities or copy number variants. However, whole-exome sequencing and Sanger sequencing revealed a de novo nonsense mutation (NM_001759.3: c.829C>T; p.Gln277X) in the CCND2 gene of the patient. Bioinformatics analysis predicted that this mutation may disrupt the structure and surface charge of the CCND2 protein. This disruption could potentially prevent polyubiquitination of CCND2, leading to its resistance against degradation. Consequently, this could drive cell division and growth by altering the activity of key cell cycle regulatory nodes, ultimately contributing to the development of MPPH. This study not only presents a new case of MPPH and expands the mutation spectrum of CCND2 but also enhances our understanding of the mechanisms connecting CCND2 with overgrowth syndromes.

Circ_0070934 promotes MGAT3 expression and inhibits epithelial-mesenchymal transition in bronchial epithelial cells by sponging miR-199a-5p.

BACKGROUND: Circular RNA (circRNA) has the potential to serve as a crucial regulator in the progression of bronchial asthma. The objective of this investigation was to elucidate the functional dynamics of the circ_0070934/miR-199a-5p/Mannoside acetylglucosaminyltransferase 3 (MGAT3) axis in the development of asthma. METHODS: Circ_0070934, miR-199a-5p and MGAT3 in peripheral venous blood of 38 asthmatic patients and 43 healthy controls were detected by qRT-PCR, and the expression of MGAT3 protein was examined by ELISA. The GSE148000 dataset was analyzed for differences in MGAT3. The BEAS-2B cells were transfected with circ_0070934 plasmid and small interfering RNA, miR-199a-5p mimics and inhibitors. The apoptosis level was detected by flow cytometry and MGAT3 was detected by qRT-PCR and Western blot. The expression of E-cadherin, N-cadherin, Vimentin was examined by Western blot. Interleukin-4 (IL-4) and IL-13 were used to co-stimulate BEAS-2B cells as an asthmatic airway epithelial cell model. BEAS-2B cells exposed to type 2 cytokines (IL-4 and IL-13) were treated with circ_0070934 plasmid, and the expression of E-cadherin, N-cadherin, and Vimentin was detected by Western blot. The binding relationships were verified using dual-luciferase reporter assay and miRNA pull-down assay. RESULTS: The expression of circ_0070934 and MGAT3 in peripheral venous blood of asthmatic patients was down-regulated, and the expression of miR-199a-5p was up-regulated. And the expression of MGAT3 was reduced in sputum of asthma patients. Down-regulating the expression of circ_0070934 could promote apoptosis of BEAS-2B cells and increase epithelial-mesenchymal transition (EMT), and this effect can be partially reversed by down-regulating miR-199a-5p. Circ_0070934 could inhibit the process of epithelial mesenchymal transition induced by IL-4 and IL-13 in BEAS-2B cells. In addition, miR-199a-5p could respectively bind to circ_0070934 and MGAT3. CONCLUSION: The findings of this study indicate that circ_0070934 may function as a competitive endogenous RNA (ceRNA) of miR-199a-5p, thereby modulating the expression of MGAT3 and impacting the process of EMT in bronchial epithelial cells. These results contribute to the establishment of a theoretical framework for advancing the prevention and treatment strategies for asthma.

LINC00158 modulates the function of BEAS-2B cells via targeting BCL11B and ameliorates OVA-LPS-induced severe asthma in mice models.

Persistent type (T) 2 airway inflammation plays an important role in the development of severe asthma. However, the molecular mechanisms leading to T2 severe asthma have yet to be fully clarified. Human normal lung epithelial cells (BEAS-2B cells) were transfected with LINC00158/BCL11B plasmid/small interfering RNA (siRNA). Levels of epithelial-mesenchymal transition (EMT)-related markers were measured using real-time qPCR (RT-qPCR) and western blot. A dual luciferase reporter assay was used to validate the targeting relationship between LINC00158 and BCL11B. The effects of LINC00158-lentivirus vector-mediated overexpression and dexamethasone on ovalbumin (OVA)/lipopolysaccharide (LPS)-induced severe asthma were investigated in mice in vivo. Our study showed that overexpression of LINC00158/BCL11B inhibited the levels of EMT-related proteins, apoptosis, and promoted the proliferation of BEAS-2B cells. BCL11B was a direct target of LINC00158. And LINC00158 targeted BCL11B to regulate EMT, apoptosis, and cell proliferation of BEAS-2B cells. Compared with severe asthma mice, LINC00158 overexpression alleviated OVA/LPS-induced airway hyperresponsiveness and airway inflammation, including reductions in T helper 2 cells factors in lung tissue and BALF, serum total- and OVA-specific IgE, inflammatory cell infiltration, and goblet cells hyperplasia. In addition, LINC00158 overexpression alleviated airway remodeling, including reduced plasma TGF-ß1 and collagen fiber deposition, as well as suppression of EMT. Additionally, overexpression of LINC00158 enhanced the therapeutic effect of dexamethasone in severe asthmatic mice models. LINC00158 regulates BEAS-2B cell biological function by targeting BCL11B. LINC00158 ameliorates T2 severe asthma in vivo and provides new insights into the clinical treatment of severe asthma.

Case report: A novel variant (H49N) in Myelin Protein Zero gene is responsible for a patient with Charcot-Marie-Tooth disease.

This report presents a case of Charcot-Marie-Tooth dominant intermediate D (CMTDID), a rare subtype of Charcot-Marie-Tooth disease, in a 52 years-old male patient. The patient exhibited mobility impairment, foot abnormalities (pes cavus), and calf muscle atrophy. Whole exome sequencing and Sanger sequencing suggested that a novel variant (NM_000530.8, c.145C>A/p.His49Asn) of MPZ may be the genetic lesion in the patient. The bioinformatic program predicted that the new variant (p.His49Asn), located at an evolutionarily conserved site of MPZ, was neutral. Our study expands the variant spectrum of MPZ and the number of identified CMTDID patients, contributing to a better understanding of the relationship between MPZ and CMTDID.

Case report: Whole exome sequencing identified a novel mutation (p.Y301H) of MAF in a Chinese family with congenital cataracts.

Background: Congenital cataracts stand as the primary cause of childhood blindness globally, characterized by clouding of the eye's lens at birth or shortly thereafter. Previous investigations have unveiled that a variant in the V-MAF avian musculoaponeurotic-fibrosarcoma oncogene homolog (MAF) gene can result in Ayme-Gripp syndrome and solitary cataract. Notably, MAF mutations have been infrequently reported in recent years. Methods: In this investigation, we recruited a Chinese family with non-syndromic cataracts. Whole exome sequencing and Sanger sequencing were applied to scrutinize the genetic anomaly within the family. Results: Through whole exome sequencing and subsequent data filtration, a new mutation (NM_005360, c.901T>C/p.Y301H) in the MAF gene was detected. Sanger sequencing validated the presence of this mutation in another affected individual. The p.Y301H mutation, situated in an evolutionarily preserved locus, was not detected in our 200 local control cohorts and various public databases. Additionally, multiple bioinformatic programs predicted that the mutation was deleterious and disrupted the bindings between MAF and its targets. Conclusion: Hence, we have documented a new MAF mutation within a Chinese family exhibiting isolated congenital cataracts. Our study has the potential to broaden the spectrum of MAF mutations, offering insights into the mechanisms underlying cataract formation and facilitating genetic counseling and early diagnosis for congenital cataract patients.

A compound heterozygous mutation of ERCC8 is responsible for a family with Cockayne syndrome.

BACKGROUND: Cockayne syndrome is an inherited heterogeneous defect in transcription-coupled DNA repair (TCR) cause severe clinical syndromes, which may affect the nervous system development of infants and even lead to premature death in some cases. ERCC8 diverse critical roles in the nucleotide excision repair (NER) complex, which is one of the disease-causing genes of Cockayne syndrome. METHODS AND RESULTS: The mutation of ERCC8 in the patient was identified and validated using WES and Sanger sequencing. Specifically, a compound heterozygous mutation (c.454_460dupGTCTCCA p. T154Sfs*13 and c.755_759delGTTTT p.C252Yfs*3) of ERCC8 (CSA) was found, which could potentially be the genetic cause of Cockayne syndrome in the proband. CONCLUSION: In this study, we identified a novel heterozygous mutation of ERCC8 in a Chinese family with Cockayne syndrome, which enlarging the genetic spectrum of the disease.

Correction to: Increased RTN3 phenocopies nonalcoholic fatty liver disease by inhibiting the AMPK-IDH2 pathway.

[This corrects the article DOI: 10.1002/mco2.226.].

Reticulon 3 regulates sphingosine-1-phosphate synthesis in endothelial cells to control blood pressure.

The discovery of the endothelium as a major regulator of vascular tone triggered intense research among basic and clinical investigators to unravel the physiologic and pathophysiologic significance of this phenomenon. Sphingosine-l-phosphate (S1P), derived from the vascular endothelium, is a significant regulator of blood pressure. However, the mechanisms underlying the regulation of S1P biosynthetic pathways in arteries remain to be further clarified. Here, we reported that Reticulon 3 (RTN3) regulated endothelial sphingolipid biosynthesis and blood pressure. We employed public datasets, patients, and mouse models to explore the pathophysiological roles of RTN3 in blood pressure control. The underlying mechanisms were studied in human umbilical vein endothelial cells (HUVECs). We reported that increased RTN3 was found in patients and that RTN3-null mice presented hypotension. In HUVECs, RTN3 can regulate migration and tube formation via the S1P signaling pathway. Mechanistically, RTN3 can interact with CERS2 to promote the selective autophagy of CERS2 and further influence S1P signals to control blood pressure. We also identified an RTN3 variant (c.116C>T, p.T39M) in a family with hypertension. Our data provided the first evidence of the association between RTN3 level changes and blood pressure anomalies and preliminarily elucidated the importance of RTN3 in S1P metabolism and blood pressure regulation.

RTN3 deficiency exacerbates cisplatin-induced acute kidney injury through the disruption of mitochondrial stability.

Reticulum 3 (RTN3) is an endoplasmic reticulum (ER) protein that has been reported to act in neurodegenerative diseases and lipid metabolism. However, the role of RTN3 in acute kidney injury (AKI) has not been explored. Here, we employed public datasets, patient data, and animal models to explore the role of RTN3 in AKI. The underlying mechanisms were studied in primary renal tubular epithelial cells and in the HK2 cell line. We found reduced expression of RTN3 in AKI patients, cisplatin-induced mice, and cisplatin-treated HK2 cells. RTN3-null mice exhibit more severe AKI symptoms and kidney fibrosis after cisplatin treatment. Mitochondrial dysfunction was also found in cells with RTN3 knockdown or knockout. A mechanistic study revealed that RTN3 can interact with HSPA9 in kidney cells. RTN3 deficiency may disrupt the RTN3-HSPA9-VDAC2 complex and affect MAMs during ER-mitochondrion contact, which further leads to mitochondrial dysfunction and exacerbates cisplatin-induced AKI. Our study indicated that RTN3 was important in the kidney and that a decrease in RTN3 in the kidney might be a risk factor for the aggravation of AKI.

Hypoxia-induced ZEB1 promotes cervical cancer immune evasion by strengthening the CD47-SIRPα axis.

BACKGROUND: The dynamic interaction between cancer cells and tumour-associated macrophages (TAMs) in the hypoxic tumour microenvironment (TME) is an active barrier to the effector arm of the antitumour immune response. Cancer-secreted exosomes are emerging mediators of this cancer-stromal cross-talk in the TME; however, the mechanisms underlying this interaction remain unclear. METHODS: Exosomes were isolated with ExoQuick exosome precipitation solution. The polarizing effect of TAMs was evaluated by flow cytometry, western blot analysis, immunofluorescence staining and in vitro phagocytosis assays. Clinical cervical cancer specimens and an in vivo xenograft model were also employed. RESULTS: Our previous study showed that hypoxia increased the expression of ZEB1 in cervical squamous cell carcinoma (CSCC) cells, which resulted in increased infiltration of TAMs. Here, we found that hypoxia-induced ZEB1 expression is closely correlated with CD47-SIRPα axis activity in CSCC, which enables cancer cells to evade phagocytosis by macrophages and promotes tumour progression. ZEB1 was found to directly activate the transcription of the CD47 gene in hypoxic CSCC cells. We further showed that endogenous ZEB1 was characteristically enriched in hypoxic CSCC cell-derived exosomes and transferred into macrophages via these exosomes to promote SIRPα+ TAM polarization. Intriguingly, exosomal ZEB1 retained transcriptional activity and reprogrammed SIRPα+ TAMs via activation of the STAT3 signalling pathway in vitro and in vivo. STAT3 inhibition reduced the polarizing effect induced by exosomal ZEB1. Knockdown of ZEB1 increased the phagocytosis of CSCC cells by macrophages via decreasing CD47 and SIRPα expression. CONCLUSIONS: Our results suggest that hypoxia-induced ZEB1 promotes immune evasion in CSCC by strengthening the CD47-SIRPα axis. ZEB1-targeted therapy in combination with CD47-SIRPα checkpoint immunotherapy may improve the outcomes of CSCC patients in part by disinhibiting innate immunity.

Nanoscaled Oxygen Carrier-Driven Chemical Looping for Carbon Neutrality: Opportunities and Challenges.

ConspectusClimate change poses unprecedented challenges, demanding efforts toward innovative solutions. Amid these efforts, chemical looping stands out as a promising strategy, attracting attention for its CO2 capture prowess and versatile applications. The chemical looping approach involves fragmenting a single reaction, often a redox reaction, into multiple subreactions facilitated by a carrier, frequently a metal oxide. This innovative method enables diverse chemical transformations while inherently segregating products, enhancing process flexibility, and fostering autothermal properties. An intriguing facet of this novel technique lies in its capacity for CO2 utilization in processes like dry reforming and gasification of carbon-based feeds such as natural gas and biomass. Central to the success of chemical looping technology is a profound understanding of the intricacies of redox chemistry within these processes. Notably, nanoscaled oxygen carriers have proven effective, characterized by their extensive surface area and customizable structure. These carriers hold substantial promise, enabling reactions under milder conditions.This Account offers a concise overview of the mechanisms, benefits, opportunities, and challenges associated with nanoscaled carriers in chemical looping applications, with a focus on CO2 utilization. We delve into the nuances of redox chemistry, shedding light on ionic diffusion and oxygen vacancy─two key elements that are crucial in designing oxygen carriers. This discussion extends to nanospecific factors such as the particle size effect and gas diffusivity. Through the application of density functional theory simulations, insights are drawn regarding the impact of nanoparticle size on syngas production in chemical looping. Interestingly, nanosized iron oxide (Fe2O3) carriers exhibit elevated syngas selectivity and constrained CO2 formation at the nanoscale. Moreover, the reactivity enhancement of mesoporous SBA-16 supported Fe2O3 over mesoporous SBA-15 supported Fe2O3 is elucidated through Monte Carlo simulations that emphasize the superiority of the 3-dimensional interconnected porous network of SBA-16 in enhancing gas diffusion, thereby amplifying reactivity compared to the 2-dimensional SBA-15. Furthermore, we explore prevalent nanoscaled carriers, focusing on their amplified performance in CO2 utilization schemes. These encompass the integration of nanoparticles with mesoporous supports to enhance surface area, the adoption of nanoscale core-shell architectures to enhance diffusion, and the dispersion of nanoscaled active sites on microsized carriers to accelerate reactant activation. Notably, our mesoporous-supported Fe2O3 nanocarrier facilitates methane dissociation and oxidation by reducing energy barriers, thereby promoting methane conversion. The Account proceeds to outline key challenges and prospects for nanoscaled carriers in chemical looping, concluding with a glance into future research directions. We also shine a spotlight on our research group's efforts in innovating oxygen carrier materials, supplemented by discussions on indispensable elements that are essential for successful scale-up deployment.

A novel mutation of CTC1 leads to telomere shortening in a chinese family with interstitial lung disease.

Interstitial lung diseases (ILDs), or diffuse pulmonary lung disease, are a subset of lung diseases that primarily affect lung alveoli and the space around interstitial tissue and bronchioles. It clinically manifests as progressive dyspnea, and patients often exhibit a varied decrease in pulmonary diffusion function. Recently, variants in telomere biology-related genes have been identified as genetic lesions of ILDs. Here, we enrolled 82 patients with interstitial pneumonia from 2017 to 2021 in our hospital to explore the candidate gene mutations of these patients via whole-exome sequencing. After data filtering, a novel heterozygous mutation (NM_025099: p.Gly131Arg) of CTC1 was identified in two affected family members. As a component of CST (CTC1-STN1-TEN1) complex, CTC1 is responsible for maintaining telomeric structure integrity and has also been identified as a candidate gene for IPF, a special kind of chronic ILD with insidious onset. Simultaneously, real-time PCR revealed that two affected family members presented with short telomere lengths, which further confirmed the effect of the mutation in the CTC1 gene. Our study not only expanded the mutation spectrum of CTC1 and provided epidemiological data on ILDs caused by CTC1 mutations but also further confirmed the relationship between heterozygous mutations in CTC1 and ILDs, which may further contribute to understanding the mechanisms underlying ILDs.

Case report: A novel WASHC5 variant altering mRNA splicing causes spastic paraplegia in a patient.

Background: Hereditary spastic paraplegia (HSP) is a progressive upper-motor neurodegenerative disease. Mutations in the WASHC5 gene are associated with autosomal dominant HSP, spastic paraplegia 8 (SPG8). However, due to the small number of reported cases, the exact mechanism remains unclear. Method: We report a Chinese family with HSP. The proband was referred to our hospital due to restless leg syndrome and insomnia. The preliminary clinical diagnosis of the proband was spastic paraplegia. Whole-exome sequencing (WES) and RNA splicing analysis were conducted to evaluate the genetic cause of the disease in this family. Results: A novel splice-altering variant (c.712-2A>G) in the WASHC5 gene was detected and further verified by RNA splicing analysis and Sanger sequencing. Real-time qPCR analysis showed that the expression of genes involved in the Wiskott-Aldrich syndrome protein and SCAR homolog (WASH) complex and endosomal and lysosomal systems was altered due to this variant. Conclusion: A novel heterozygous splice-altering variant (c.712-2A>G) in the WASHC5 gene was detected in a Chinese family with HSP. Our study provided data for genetic counseling to this family and offered evidence that this splicing variant in the WASHC5 gene is significant in causing HSP.