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Background: Carbamoyl phosphate synthetase 1 (CPS1) deficiency (OMIM 237300), an autosomal recessive rare and severe urea cycle disorder, is associated with hyperammonemia and high mortality., Methods: Herein we present 12 genetic variants identified in seven clinically well-characterized Chinese patients with CPS1 deficiency who were admitted to the Children's Medical Center of Peking University First Hospital from September 2014 to August 2023., Results: Seven patients (two male and five female patients including two sisters) experienced symptoms onset between 2 days and 13 years of age, and they were diagnosed with CPS1 deficiency between 2 months and 20 years. Peak blood ammonia levels ranged from 160 to 1,000 µmol/L. Three patients showed early-onset CPS1 deficiency, with only one surviving after treatment with sodium phenylbutyrate, N-carbamoyl-L-glutamate, and liver transplantation at 4 months, showing a favorable outcome. The remaining four patients had late-onset CPS1 deficiency, presenting with mental retardation, psychiatric symptoms, and self-selected low-protein diets. Among the 12 CPS1 variants identified in these patients, 10 were novel, with all patients exhibiting compound heterozygosity for CPS1 mutant alleles. Seven variants (c.149T > C, c.616 A > T, c.1145 C > T, c.1294G > A, c.3029 C > T, c.3503 A > T, and c.3793 C > T) resulted in single amino acid substitutions. Three frameshift variations (c.2493del, c.3067dup, and c.3241del) were identified, leading to enzyme truncation. One mutation (c.3506_3508del) caused an in-frame single amino acid deletion, while another (c.2895 + 2T > C) resulted in aberrant splicing., Conclusions: Except for two known variants, all other variants were identified as novel. No hotspot variants were observed among the patients. Our data contribute to expanding the mutation spectrum of CPS1., (© 2024. The Author(s).)

Background: Leigh syndrome (LS) is a common mitochondrial disease caused by mutations in both mitochondrial and nuclear genes. Isoleucyl-tRNA synthetase 2 (IARS2) encodes mitochondrial isoleucine-tRNA synthetase, and variants in IARS2 have been reported to cause LS. However, the pathogenic mechanism of IARS2 variants is still unclear., Methods: Two unrelated patients, a 4-year-old boy and a 5-year-old boy diagnosed with LS, were recruited, and detailed clinical data were collected. The DNA of the patients and their parents was isolated from the peripheral blood for the identification of pathogenic variants using next-generation sequencing and Sanger sequencing. The ClustalW program, allele frequency analysis databases (gnomAD and ExAc), and pathogenicity prediction databases (Clinvar, Mutation Taster and PolyPhen2) were used to predict the conservation and pathogenicity of the variants. The gene expression level, oxygen consumption rate (OCR), respiratory chain complex activity, cellular adenosine triphosphate (ATP) production, mitochondrial membrane potential (MMP) and mitochondrial reactive oxygen species (ROS) levels were measured in patient-derived lymphocytes and IARS2-knockdown HEK293T cells to evaluate the pathogenicity of the variants., Results: We reported 2 unrelated Chinese patients manifested with LS who carried biallelic IARS2 variants (c.1_390del and c.2450G > A from a 4-year-old boy, and c.2090G > A and c.2122G > A from a 5-year-old boy), of which c.1_390del and c.2090G > A were novel. Functional studies revealed that the patient-derived lymphocytes carrying c.1_390del and c.2450G > A variants exhibited impaired mitochondrial function due to severe mitochondrial complexes I and III deficiencies, which was also found in IARS2-knockdown HEK293T cells. The compensatory experiments in vitro cell models confirmed the pathogenicity of IARS2 variants since re-expression of wild-type IARS2 rather than mutant IARS2 could rescue complexes I and III deficiency, oxygen consumption, and cellular ATP content in IARS2 knockdown cells., Conclusion: Our results not only expand the gene mutation spectrum of LS, but also reveal for the first time the pathogenic mechanism of IARS2 variants due to a combined deficiency of mitochondrial complexes I and III, which is helpful for the clinical diagnosis of IARS2 mutation-related diseases., (© 2024. The Author(s).)

The growing demand for clean energy has heightened interest in sodium-ion batteries (SIBs) as promising candidates for large-scale energy storage. However, the sluggish reaction kinetics and significant volumetric changes in anode materials present challenges to the electrochemical performance of SIBs. This work introduces a hierarchical structure where WS 2 is confined between an inner hard carbon core and an outer nitrogen-doped carbon shell, forming HC@WS 2 @NCs core-shell structures as anodes for SIBs. The inner hard carbon core and outer nitrogen-doped carbon shell anchor WS 2 , enhancing its structural integrity. The highly conductive carbon materials accelerate electron transport during charge/discharge, while the rationally constructed interfaces between carbon and WS 2 regulate the interfacial energy barrier and electric field distribution, improving ion transport. This synergistic interaction results in superior electrochemical performance: the HC@WS 2 @NCs anode delivers a high capacity of 370 mAh g -1 at 0.2 A/g after 200 cycles and retains261 mAh g -1 at 2 A/g after 2000 cycles. In a full battery with a Na 3 V 2 (PO 4 ) 3 cathode, the Na 3 V 2 (PO 4 ) 3 //HC@WS 2 @NC full-cell achieves an impressive initial capacity of 220 mAh g -1 at 1 A/g. This work provides a strategic approach for the systematic development of WS 2 -based anode materials for SIBs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

The escalating global demand for clean energy has spurred substantial interest in sodium-ion batteries (SIBs) as a promising solution for large-scale energy storage systems. However, the insufficient reaction kinetics and considerable volume changes inherent to anode materials present significant hurdles to enhancing the electrochemical performance of SIBs. In this study, hierarchical MoS 2 /WS 2 heterostructures were constructed into dual carbon layers (HC@MoS 2 /WS 2 @NC) and assessed their suitability as anodes for SIBs. The internal hard carbon core (HC) and outer nitrogen-doped carbon shell (NC) effectively anchor MoS 2 /WS 2 , thereby significantly improving its structural stability. Moreover, the conductive carbon components expedite electron transport during charge-discharge processes. Critically, the intelligently engineered interface between MoS 2 and WS 2 modulates the interfacial energy barrier and electric field distribution, promoting faster ion transport rates. Capitalizing on these advantageous features, the HC@MoS 2 /WS 2 @NC nanocomposite exhibits outstanding electrochemical performance when utilized as an anode in SIBs. Specifically, it delivers a high capacity of 415 mAh/g at a current density of 0.2 A/g after 100 cycles. At a larger current density of 2 A/g, it maintains a commendable capacity of 333 mAh/g even after 1000 cycles. Additionally, when integrated into a full battery configuration with a Na 3 V 2 (PO 4 ) 3 cathode, the Na 3 V 2 (PO 4 ) 3 //HC@MoS 2 /WS 2 @NC full cell delivers a high capacity of 120 mAh/g after 300 cycles at 1 A/g. This work emphasizes the substantial improvement in battery performance that can be attained through the implementation of dual carbon confinement, offering a constructive approach to guide the design and development of next-generation anode materials for SIBs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Premature Ventricular Complexes (PVCs) are very common in clinical practice, with frequent PVCs (more than 30 beats per hour) or polymorphic PVCs significantly increasing the risk of mortality. Previous studies have shown that vagus nerve stimulation improves ventricular arrhythmias. Stimulation of the auricular distribution of the vagus nerve has proven to be a simple, safe, and effective method to activate the vagus nerve. Transcutaneous au ricular vagus nerve stimulation (taVNS) has shown promise in both clinical and experimental setting for PVCs; however, high-quality clinical studies are lacking, resulting in insufficient evidence of efficacy., Methods: The study is a prospective, randomized, parallel-controlled trial with a 1:1 ratio between the two groups. Patients will be randomized to either the treatment group (taVNS) or the control group (Sham-taVNS) with a 6-week treatment and a subsequent 12-week follow-up period. The primary outcome is the proportion of patients with a ≥ 50% reduction in the number of PVCs monitored by 24-hour Holter. Secondary outcomes include the proportion of patients with a ≥ 75% reduction in PVCs, as well as the changes in premature ventricular beats, total heartbeats, and supraventricular premature beats recorded by 24-hour Holter. Additional assessments compared score changes in PVCs-related symptoms, as well as the score change of self-rating anxiety scale (SAS), self-rating depression scale (SDS), and 36-item short form health survey (SF-36)., Discussion: The TASC-V trial will help to reveal the efficacy and safety of taVNS for frequent PVCs, offering new clinical evidence for the clinical practice., Trial Registration: Clinicaltrials.gov: NCT04415203 (Registration Date: May 30, 2020)., (© 2024. The Author(s).)

Sonodynamic therapy (SDT), featuring noninvasive, deeper penetration, low cost, and repeatability, is a promising therapy approach for deep-seated tumors. However, the general or only utilization of SDT shows low efficiency and unsatisfactory treatment outcomes due to the complicated tumor microenvironment (TME) and SDT process. To circumvent the issues, three feasible approaches for enhancing SDT-based therapeutic effects, including sonosensitizer optimization, strategies for conquering hypoxia TME, and combinational therapy are summarized, with a particular focus on the combination therapy of SDT with other therapy modalities, including chemodynamic therapy, photodynamic therapy, photothermal therapy, chemotherapy, starvation therapy, gas therapy, and immunotherapy. In the end, the current challenges in SDT-based therapy on tumors are discussed and feasible approaches for enhanced therapeutic effects are provided. It is envisioned that this review will provide new insight into the strategic design of high-efficiency sonosensitizer-derived nanotheranostics, thereby augmenting SDT and accelerating the potential clinical transformation., (© 2024 Wiley‐VCH GmbH.)

The aim of the study was to evaluate the ability of a modified passive deflation needle to reduce the apical voids during the intra-canal iRoot SP sealer injection. A modified passive deflation injection needle was designed. Forty 20°-curved and twenty S-shaped single-canal resin block models were allocated into six groups. Each group was mechanically prepared to #25/04 or #25/06 file; then the root canals were injected with iRoot SP sealer using a modified needle or a normal plastic needle. Radiographs were taken to measure the length of apical void in each specimen. Similarly, twenty single-canal extracted premolars were collected and randomly divided into four groups. Each group was prepared to #25/04 or #25/06 file; then the root canals were injected with iRoot SP sealer using a modified needle or a normal plastic needle. Roots were then scanned using micro-computed tomography (micro-CT), and the volume of voids in root canals was analyzed and compared among groups. Statistical analysis demonstrated that the length and the volumetric percentage of voids were much lower in the modified needle group in both resin block root canal models and extract teeth than the normal plastic needle group (P < 0.05). The modified passive deflation needle can efficiently reduce apical voids during the intra-canal iRoot SP sealer injection., (© 2024. The Author(s), under exclusive licence to The Society of The Nippon Dental University.)

DEAD-box helicase 53 (DDX53) is a member of the DEAD-box protein family of RNA helicases. Unlike other family members that are responsible for RNA metabolism, the biological function of DDX53 and its impact on the human condition are unclear. Herein, we found a full-length DDX53 deletion mutation in a hereditary spastic paraplegia-like (HSP-like) patient with lower extremity spasticity, walking disorder, visual impairment, and lateral ventricular white matter lesions. Bioinformatic analysis revealed that DDX53 was mainly expressed in the cerebellar cortex and may function as a tissue-specific RNA helicase. Transcriptome analysis showed that the expression of multiple brain-associated genes involved in synapse organization, neuron function, and neuromuscular junctions was affected by DDX53 depletion. Moreover, RNA immunoprecipitation sequencing (RIP-seq) analysis showed that DDX53 interacted with 176 genes, and 96 of these genes were associated with the execution of neurofunction, particularly in the regulation of cell projection organization and nervous system development. Collectively, although a more specified cell or animal model is required to fully understand the functional role of DDX53 in the human brain, we report for the first time that the patient with DDX53 defects exhibits HSP-like symptoms and that DDX53 is essential for maintaining neuronal function, with loss-of-function mutation in DDX53 potentially leading to HSP due to impaired RNA metabolism in the nervous system. KEY MESSAGES: DDX53 deficiency was first reported to be associated with HSP disorder. DDX53 exhibited minimal impact on mitochondrial function. DDX53 impaired RNA metabolism in the nervous system., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Ferroptosis is a novel style of cell death, and studies have shown that ferroptosis is strongly associated with spinal cord injury (SCI). A large number of ferroptosis inhibitors have been reported, but so far no ferroptosis inhibitor has been used clinically. Therefore there is an urgent need to discover a better inhibitor of ferroptosis. In this study, 24 novel sulfonamide phenothiazine ferroptosis inhibitors were designed and synthesized, followed by structure-activity relationship studies on these compounds. Among them, compound 23b exhibited the best activity in Erastin-induced PC12 cells (EC 50  = 0.001 μM) and demonstrated a low hERG inhibition activity (IC 50  > 30 μM). Additionally, compound 23b was identified as a ROS scavenger and showed promising therapeutic effects in an SD rat model of SCI. Importantly, 23b did not display significant toxicity in both in vivo and in vitro experiments and show good pharmacokinetic properties. These findings suggest that compound 23b, a novel ferroptosis inhibitor, holds potential as a therapeutic agent for spinal cord injury and warrants further investigation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Natural organic matter (NOM) can impede the removal of organic micro-pollutants (OMPs) through several mechanisms, including inner filter effect, competition with the target OMP, and radical scavenging, during synchronous adsorption/photocatalysis of multi-functional composites. In this study, the fate and inhibitory mechanisms of sulfamerazine (SMZ, a model OMP) that occurred in presence of seven different NOM samples (i.e. three standard NOM surrogates, a river water sample, a carbon filter effluent and two different sand filter effluents) during the adsorption/photocatalysis by a composite of Bi 2 O 3 -TiO 2 supported on powdered activated carbon (Bi 2 O 3 -TiO 2 /PAC, abbreviated as BTP) when exposed to visible light irradiation were revealed. The results indicated that adsorption played a greater attribution than photocatalysis on SMZ removal. The primary impediment to the adsorption and photocatalytic degradation of SMZ was attributed to the presence of terrestrial-derived, humic-like NOM fractions with high aromaticity. The adsorption efficacy of SMZ was weakened by the absorption of NOM and its degradation products onto the BTP surface. The inner filter effect, competition between NOM and SMZ, and radical scavenging were responsible for the reduced photocatalysis of SMZ. In the cases of real water matrices, the presence of inorganic anion and co-existed NOM reduced the removal of SMZ. In summary, the findings of this work offer a comprehensive comprehension of the impact of NOM fractions on photocatalysis, emphasizing the necessity to examine the interplay between NOM and background inorganic constituents in the degradation of OMP via adsorption/photocatalysis.

In recent years, aqueous zinc-ion batteries (ZIBs) have emerged as a prominent research topic due to their inherent safety attributes, relatively low cost, and comparatively higher energy density. However, the challenges associated with the zinc metal anode in the form of dendrite formation, hydrogen evolution, and severe side reactions have proven to be particularly vexing. Thus, it is imperative to investigate novel intercalation-type anode materials for ZIBs that exhibit exceptional structural properties and appropriate redox potentials based on conversion mechanisms. In this work, through adding polyvinylpyrrolidone (PVP) surfactant to precursors and tailoring reaction time, hierarchical CuS hollow spheres are successfully constructed by a facile one-step hydrothermal process. When applied as an anode in ZIBs, the hollow hierarchical CuS with large surface area can effectively reduce the transport distance of electrons and Zn 2+ and alleviate volume expansion during the insertion/extraction of Zn 2+ . The hierarchical CuS hollow spheres prepared over 8 h (CuS-8) exhibit a specific capacity of 126 mAh/g and long-term cycle life (1500 cycles) at a current density of 3 A/g. In addition, CuS-8//MnO 2 @CNTs full-cell shows a capacity retention of 117 mAh/g after 300 cycles at 1 A/g current density, which proves the advantage of hierarchical CuS hollow spheres in serving as an efficient and durable anode material for ZIBs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Backgroud: Routine metabolic assessments for methylmalonic acidemia (MMA), propionic acidemia (PA), and homocysteinemia involve detecting metabolites in dried blood spots (DBS) and analyzing specific biomarkers in serum and urine. This study aimed to establish a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous detection of three specific biomarkers (methylmalonic acid, methylcitric acid, and homocysteine) in DBS, as well as to appraise the applicability of these three DBS metabolites in monitoring patients with MMA, PA, and homocysteinemia during follow-up., Methods: A total of 140 healthy controls and 228 participants were enrolled, including 205 patients with MMA, 17 patients with PA, and 6 patients with homocysteinemia. Clinical data and DBS samples were collected during follow-up visits., Results: The reference ranges (25th-95th percentile) for DBS methylmalonic acid, methylcitric acid, and homocysteine were estimated as 0.04-1.02 μmol/L, 0.02-0.27 μmol/L and 1.05-8.22 μmol/L, respectively. Following treatment, some patients achieved normal metabolite concentrations, but the majority still exhibited characteristic biochemical patterns. The concentrations of methylmalonic acid, methylcitric acid, and homocysteine in DBS showed positive correlations with urine methylmalonic acid ( r  = 0.849, p  < 0.001), urine methylcitric acid ( r  = 0.693, p  < 0.001), and serum homocysteine ( r  = 0.721, p  < 0.001) concentrations, respectively. Additionally, higher levels of DBS methylmalonic acid and methylcitric acid may be associated with increased cumulative complication scores., Conclusion: The LC-MS/MS method established in this study reliably detects methylmalonic acid, methylcitric acid, and homocysteine in DBS. These three DBS metabolites can be valuable for monitoring patients with MMA, PA, and homocysteinemia during follow-up. Further investigation is required to determine the significance of these DBS biomarkers in assessing disease burden over time., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Ma, Kang, Jin, Li, Song, Li, Cao and Yang.)

The henipaviruses, including Nipah virus (NiV) and Hendra virus (HeV), are biosafety level 4 (BSL-4) zoonotic pathogens that cause severe neurological and respiratory disease in humans. To study the replication machinery of these viruses, we developed robust minigenome systems that can be safely used in BSL-2 conditions. The nucleocapsid (N), phosphoprotein (P), and large protein (L) of henipaviruses are critical elements of their replication machinery and thus essential support components of the minigenome systems. Here, we tested the effects of diverse combinations of the replication support proteins on the replication capacity of the NiV and HeV minigenomes by exchanging the helper plasmids coding for these proteins among the two viruses. We demonstrate that all combinations including one or more heterologous proteins were capable of replicating both the NiV and HeV minigenomes. Sequence alignment showed identities of 92% for the N protein, 67% for P, and 87% for L. Notably, variations in amino acid residues were not concentrated in the N-P and P-L interacting regions implying that dissimilarities in amino acid composition among NiV and HeV polymerase complex proteins may not impact their interactions. The observed indiscriminate activity of NiV and HeV polymerase complex proteins is different from related viruses, which can support the replication of heterologous genomes only when the whole polymerase complex belongs to the same virus. This newly observed promiscuous property of the henipavirus polymerase complex proteins likely attributed to their conserved interaction regions could potentially be harnessed to develop universal anti-henipavirus antivirals.IMPORTANCEGiven the severity of disease induced by Hendra and Nipah viruses in humans and the continuous emergence of new henipaviruses as well as henipa-like viruses, it is necessary to conduct a more comprehensive investigation of the biology of henipaviruses and their interaction with the host. The replication of henipaviruses and the development of antiviral agents can be studied in systems that allow experiments to be performed under biosafety level 2 conditions. Here, we developed robust minigenome systems for the Nipah virus (NiV) and Hendra virus (HeV) that provide a convenient alternative for studying NiV and HeV replication. Using these systems, we demonstrate that any combination of the three polymerase complex proteins of NiV and HeV could effectively initiate the replication of both viral minigenomes, which suggests that the interaction regions of the polymerase complex proteins could be effective targets for universal and effective anti-henipavirus interventions., Competing Interests: The authors declare no conflict of interest.

Background and Aims: To investigate the clinical features, ALDH5A1 gene variations, treatment, and prognosis of patients with succinic semialdehyde dehydrogenase (SSADH) deficiency., Materials and Methods: This retrospective study evaluated the findings in 13 Chinese patients with SSADH deficiency admitted to the Pediatric Department of Peking University First Hospital from September 2013 to September 2023., Results: Thirteen patients (seven male and six female patients; two sibling sisters) had the symptoms aged from 1 month to 1 year. Their urine 4-hydroxybutyrate acid levels were elevated and were accompanied by mildly increased serum lactate levels. Brain magnetic resonance imaging (MRI) showed symmetric abnormal signals in both sides of the globus pallidus and other areas. All 13 patients had psychomotor retardation, with seven showing epileptic seizures. Among the 18 variants of the ALDH5A1 gene identified in these 13 patients, six were previously reported, while 12 were novel variants. Among the 12 novel variants, three (c.85&#95;116del, c.206&#95;222dup, c.762C > G) were pathogenic variants; five (c.427delA, c.515G > A, c.637C > T, c.755G > T, c.1274T > C) were likely pathogenic; and the remaining four (c.454G > C, c.479C > T, c.1480G > A, c.1501G > C) were variants of uncertain significance. The patients received drugs such as L-carnitine, vigabatrin, and taurine, along with symptomatic treatment. Their urine 4-hydroxybutyric acid levels showed variable degrees of reduction., Conclusions: A cohort of 13 cases with early-onset SSADH deficiency was analyzed. Onset of symptoms occurred from 1 month to 1 year of age. Twelve novel variants of the ALDH5A1 gene were identified., (© 2024. The Author(s).)

In recent years, with the acceleration of industrialization, the decline of male fertility caused by heavy metal pollution has attracted much attention. However, whether the inhibition of testicular function after cadmium exposure is reversible remains to be studied. In this study, we constructed rat models of cadmium exposure and dis-exposure, and collected relative samples to observe the changes of related indicators. The results showed that cadmium exposure could reduce the fertility, inhibit the hypothalamic-pituitary-testis axis and activate hypothalamic-pituitary-adrenal axis function, the testicular GR/PI3K-AKT/AMPK signal was abnormal, cell proliferation was inhibited and apoptosis was enhanced. Four weeks after the exposure was stopped, the fertility was still decreased, testicular testosterone synthesis and spermatogenesis were inhibited, cell proliferation was inhibited and apoptosis was enhanced, but all of them were reversed. After eight weeks of cadmium exposure, the above indicators were observed to return to normal. At the same time, by giving different concentrations of corticosterone to spermatogonium, we confirmed that corticosterone may regulate the proliferation and apoptosis of spermatogonium through GR/PI3K-AKT/AMPK signal. In this study, the reproductive toxicity of cadmium, a metal environmental pollutant, was analyzed in depth to provide a new theoretical and experimental basis for ensuring male reproductive health., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Neurofilaments are neuron specific skeleton proteins maintaining axon transduction speed, leaked into cerebrospinal fluid and serum after axonal injury or neuron death. Sleep duration change has long related to many health issues but lack laboratory examination., Methods: This study enrolled total 10,175 participants from 2013 to 2014 National Health and Nutrition Examination Survey and used a multi-variable linear model to analyze the relationship between sleep duration and serum neurofilament light chain (sNfL) level., Results: There was a fixed relationship between sleep duration and sNfL level (β = 0.65, p  = 0.0280). After adjusted for covariates, this relationship still (β = 0.82, p  = 0.0052). Segmented regression showed that the turning point of sleep duration was 7 h 1 h decrease in sleep duration was significantly associated with -1.26 higher sNfL level (95 % CI: 2.25, -0.28; p  = 0.0115) when sleep duration <7 h; however, 1 h increase in sleep duration was significantly associated with 3.20 higher sNfL level (95 % CI: 2.13, 4.27; p  < 0.0001) when sleep duration >7 h. Furthermore, the stratified analysis indicated that the associations between sleep duration and sNfL level were stronger among those normal body mass index and trouble sleeping ( p -interaction <0.0001 and 0.0003)., Conclusion: In summary, there was a J-shaped relationship between sleep duration and sNfL level in the United States of America representative group, these may suggest that extreme sleep duration can be deleterious judged by sNfL level. And still need large cohort study to determine the accurate relationship, and cluster analysis to infer the nervous disease connected with extreme sleep duration., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: This study aims to evaluate the ability of laboratories to perform spinal muscular atrophy (SMA) genetic testing in newborns based on dried blood spot (DBS) samples, and to provide reference data and advance preparation for establishing the pilot external quality assessment (EQA) scheme for SMA genetic testing of newborns in China., Methods: The pilot EQA scheme contents and evaluation principles of this project were designed by National Center for Clinical Laboratories (NCCL), National Health Commission. Two surveys were carried out in 2022, and 5 batches of blood spots were submitted to the participating laboratory each time. All participating laboratories conducted testing upon receiving samples, and test results were submitted to NCCL within the specified date., Results: The return rates were 75.0% (21/28) and 95.2% (20/21) in the first and second surveys, respectively. The total return rate of the two examinations was 83.7% (41/49). Nineteen laboratories (19/21, 90.5%) had a full score passing on the first survey, while in the second survey twenty laboratories (20/20, 100%) scored full., Conclusions: This pilot EQA survey provides a preliminary understanding of the capability of SMA genetic testing for newborns across laboratories in China. A few laboratories had technical or operational problems in testing. It is, therefore, of importance to strengthen laboratory management and to improve testing capacity for the establishment of a national EQA scheme for newborn SMA genetic testing.

Objectives: This study aimed to design a modified passive-deflation sealer injection needle and investigate its ability to improve obturation quality of single-cone technique through assessing the distribution of voids in root canals using micro-computed tomography (micro-CT)., Materials and Methods: Forty-eight mandibular incisors were divided into eight groups (n = 6), according to the taper of root canal preparation (0.06 or 0.04), the needle used for sealer injection (modified or commercial iRoot SP injection needle), and the obturation method (iRoot SP sealer-only or single-cone obturation). After obturation, each specimen was scanned by micro-CT. The volumetric percentage and distribution of all voids were first analyzed and compared among groups, then the open and closed voids were separately analyzed and compared among single-cone obturation groups., Results: Compared to commercial needle groups, modified needle groups showed much less voids, especially in the apical root canal part (P < 0.05). Besides, the modified needle groups produced much less open voids than commercial needle groups despite the root canal taper (P < 0.05)., Conclusions: The modified passive deflation sealer injection needle could effectively improve the quality of single-cone obturation through reducing intra-canal voids, especially open voids throughout the root canal, thus might possibly be developed as an effective intra-canal sealer delivering instrument., (© 2024. The Author(s).)

Background: Clinicians traditionally aim to identify a singular explanation for the clinical presentation of a patient; however, in some cases, the diagnosis may remain elusive or fail to comprehensively explain the clinical findings. In recent years, advancements in next-generation sequencing, including whole-exome sequencing, have led to the incidental identification of dual diagnoses in patients. Herein we present the cases of five pediatric patients diagnosed with dual rare genetic diseases. Their natural history and diagnostic process were explored, and lessons learned from utilizing next-generation diagnostic technologies have been reported., Results: Five pediatric cases (3 boys, 2 girls) with dual diagnoses were reported. The age at diagnosis was from 3 months to 10 years. The main clinical presentations were psychomotor retardation and increased muscular tension, some accompanied with liver dysfunction, abnormal appearance, precocious puberty, dorsiflexion restriction and varus of both feet, etc. After whole-exome sequencing, nine diseases were confirmed in these patients: Angelman syndrome and Krabbe disease in case 1, Citrin deficiency and Kabuki syndrome in case 2, Homocysteinemia type 2 and Copy number variant in case 3, Isolated methylmalonic acidemia and Niemann-Pick disease type B in case 4, Isolated methylmalonic acidemia and 21-hydroxylase deficiency in case 5. Fifteen gene mutations and 2 CNVs were identified. Four novel mutations were observed, including c.15292de1A in KMT2D, c.159&#95;164inv and c.1427G > A in SLC25A13, and c.591 C > G in MTHFR., Conclusions: Our findings underscore the importance of clinicians being vigilant about the significance of historical and physical examination. Comprehensive clinical experience is crucial for identifying atypical clinical features, particularly in cases involving dual rare genetic diseases., (© 2024. The Author(s).)

Background: We aimed to evaluate the diagnostic capabilities of Chinese laboratories for inherited metabolic disorders (IMDs) using gas chromatography-mass spectrometry (GC-MS) on urine samples. Meanwhile, based on the result of the pilot external quality assessment (EQA) scheme, we hope to establish a standardized and reliable procedure for future EQA practice., Methods: We recruited laboratories that participated in the EQA of quantitative analysis of urinary organic acids with GC-MS before joining the surveys. In each survey, a set of five real urine samples was distributed to each participant. The participants should analyze the sample by GC-MS and report the "analytical result", "the most likely diagnosis", and "recommendation for further tests" to the NCCL before the deadline., Results: A total of 21 laboratories participated in the scheme. The pass rates were 94.4% in 2020 and 89.5% in 2021. For all eight IMDs tested, the analytical proficiency rates ranged from 84.7% - 100%, and the interpretational performance rate ranged from 88.2% - 97.0%. The performance on hyperphenylalaninemia (HPA), 3-methylcrotonyl-CoA carboxylase deficiency (MCCD), and ethylmalonic encephalopathy (EE) samples were not satisfactory., Conclusions: In general, the participants of this pilot EQA scheme are equipped with the basic capability for qualitative organic acid analysis and interpretation of the results. Limited by the small size of laboratories and samples involved, this activity could not fully reflect the state of clinical practice of Chinese laboratories. NCCL will improve the EQA scheme and implement more EQA activities in the future.

Optically active organic nanoparticles capable of emitting strong near-infrared II (NIR-II) fluorescence and eliciting tumor hyperthermia are promising for tumor imaging and photothermal therapy (PTT). However, their applications for the treatment of pancreatic tumors via mere PTT are challenging as both the nanoparticles and light are hard to enter the deeply located pancreatic tumors. Here, we report a NIR-II light excitable, carbonic anhydrase (CA)-targeting cisplatin prodrug-decorated nanoparticle (IRNPs-SBA/Pt IV ) for NIR-II fluorescence imaging (FLI)-guided combination PTT and chemotherapy of pancreatic tumors. IRNPs-SBA/Pt IV is designed to hold a high photothermal conversion efficiency (PCE ≈ 65.17 %) under 1064 nm laser excitation, a strong affinity toward CA (K d  = 14.40 ± 5.49 nM), and a prominent cisplatin release profile in response to glutathione (GSH) and 1064 nm laser irradiation. We show that IRNPs-SBA/Pt IV can be actively delivered into pancreatic tumors where the CA is upregulated, and emits NIR-II fluorescence to visualize tumors with a high sensitivity and penetration depth under 980 nm laser excitation. Moreover, the tumor-resided IRNPs-SBA/Pt IV can efficiently inhibit the CA activity and consequently, relieve the acidic and hypoxic tumor microenvironment, benefiting to intensify chemotherapy. Guided by the NIR-II FLI, IRNPs-SBA/Pt IV is capable of efficiently inhibiting pancreatic tumor growth via combinational PTT and chemotherapy with 1064 nm laser excitation under a low-power density (0.5 W cm -2 , 10 min). This study demonstrates promise to fabricate NIR-II excitable nanoparticles for FLI-guided precise theranostics of pancreatic tumors., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Nonalcoholic steatohepatitis (NASH) is the advanced stage of nonalcoholic fatty liver disease (NAFLD), one of the most prevalent chronic liver diseases. The effectiveness of bariatric surgery in treating NASH and preventing or even reversing liver fibrosis has been demonstrated in numerous clinical studies, but the underlying mechanisms and crucial variables remain unknown., Methods: Using the GSE135251 dataset, we examined the gene expression levels of NASH and healthy livers. Then, the differentially expressed genes (DEGs) of patients with NASH, at baseline and one year after bariatric surgery, were identified in GSE83452. We overlapped the hub genes performed by protein-protein interaction (PPI) networks and DEGs with different expression trends in both datasets to obtain key genes. Genomic enrichment analysis (GSEA) and genomic variation analysis (GSVA) were performed to search for signaling pathways of key genes. Meanwhile, key molecules that regulate the key genes are found through the construction of the ceRNA network. NASH mice were induced by a high-fat diet (HFD) and underwent sleeve gastrectomy (SG). We then cross-linked the DEGs in clinical and animal samples using quantitative polymerase chain reaction (qPCR) and validated the key genes., Results: Seven key genes (FASN, SCD, CD68, HMGCS1, SQLE, CXCL10, IGF1) with different expression trends in GSE135251 and GSE83452 were obtained with the top 30 hub genes selected by PPI. The expression of seven key genes in mice after SG was validated by qPCR. Combined with the qPCR results from NASH mice, the four genes FASN, SCD, HMGCS1, and CXCL10 are consistent with the biological analysis. The GSEA results showed that the 'cholesterol homeostasis' pathway was enriched in the FASN, SCD, HMGCS1, and SQLE high-expression groups. The high-expression groups of CD68 and CXCL10 were extremely enriched in inflammation-related pathways. The construction of the ceRNA network obtained microRNAs and ceRNAs that can regulate seven key genes expression., Conclusion: In summary, this study contributes to our understanding of the mechanisms by which bariatric surgery improves NASH, and to the development of potential biomarkers for the treatment of NASH., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chen, Deng, Sun, Bai, Wang and Yang.)

Background: Mitochondrial diseases are heterogeneous in terms of clinical manifestations and genetic characteristics. The dynamin 1-like gene (DNM1L) encodes dynamin-related protein 1 (DRP1), a member of the GTPases dynamin superfamily responsible for mitochondrial and peroxisomal fission. DNM1L variants can lead to mitochondrial fission dysfunction., Case Presentation: Herein, we report a distinctive clinical phenotype associated with a novel variant of DNM1L and review the relevant literature. A 5-year-old girl presented with paroxysmal hemiplegia, astigmatism, and strabismus. Levocarnitine and coenzyme Q 10 supplement showed good efficacy. Based on the patient's clinical data, trio whole-exome sequencing (trio-WES) and mtDNA sequencing were performed to identify the potential causative genes, and Sanger sequencing was used to validate the specific variation in the proband and her family members. The results showed a novel de novo heterozygous nonsense variant in exon 20 of the DNM1L gene, c.2161C>T, p.Gln721Ter, which is predicted to be a pathogenic variant according to the ACMG guidelines. The proband has a previously undescribed clinical manifestation, namely hemiparesis, which may be an additional feature of the growing phenotypic spectrum of DNM1L-related diseases., Conclusion: Our findings elucidate a novel variant in DNM1L-related disease and reveal an expanding phenotypic spectrum associated with DNM1L variants. This report highlights the necessity of next generation sequencing for early diagnosis of patients, and that further clinical phenotypic and genotypic analysis may help to improve the understanding of DNM1L-related diseases., (© 2024. The Author(s).)

We report here a tumor-pretargted theranostic approach for multimodality imaging-guided synergistic cancer PDT by cascade alkaline phosphatase (ALP)-mediated in situ self-assembly and bioorthogonal inverse electron demand Diels-Alder (IEDDA) reaction. Using the enzymatic catalysis of ALP that continuously catalyses the dephosphorylation and self-assembly of trans-cyclooctene (TCO)-bearing P-FFGd-TCO, a high density of fluorescent and magnetic TCO-containing nanoparticles (FMNPs-TCO) can be synthesized and retained on the membrane of tumor cells. They can act as 'artificial antigens' amenable to concurrently capture lately administrated tetrazine (Tz)-decorated PS (775NP-Tz) and carbonic anhydrase (CA) inhibitor (SA-Tz) via the fast IEDDA reaction. This two-step pretargeting process can further induce FMNPs-TCO regrowth into microparticles (FMNPs-775/SA) directly on tumor cell membranes, which is analyzed by bio-SEM and fluorescence imaging. Thus, efficient enrichment of both SA-Tz and 775NP-Tz in tumors can be achieved, allowing to alleviate hypoxia by continuously inhibiting CA activity and improving PDT of tumors. Findings show that subcutaneous HeLa tumors could be completely eradicated and no tumor recurred after irradiation with an 808 nm laser (0.33 W cm -2 , 10 min). This pretargeted approach may be applied to enrich other therapeutic agents in tumors to improve targeted therapy., (© 2023 Wiley-VCH GmbH.)

Background: Osteoporosis (OP) is a chronic bone metabolic disease and a serious global public health problem. Several studies have shown that mitophagy plays an important role in bone metabolism disorders; however, its role in osteoporosis remains unclear. Methods: The Gene Expression Omnibus (GEO) database was used to download GSE56815, a dataset containing low and high BMD, and differentially expressed genes (DEGs) were analyzed. Mitochondrial autophagy-related genes (MRG) were downloaded from the existing literature, and highly correlated MRG were screened by bioinformatics methods. The results from both were taken as differentially expressed (DE)-MRG, and Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed. Protein-protein interaction network (PPI) analysis, support vector machine recursive feature elimination (SVM-RFE), and Boruta method were used to identify DE-MRG. A receiver operating characteristic curve (ROC) was drawn, a nomogram model was constructed to determine its diagnostic value, and a variety of bioinformatics methods were used to verify the relationship between these related genes and OP, including GO and KEGG analysis, IP pathway analysis, and single-sample Gene Set Enrichment Analysis (ssGSEA). In addition, a hub gene-related network was constructed and potential drugs for the treatment of OP were predicted. Finally, the specific genes were verified by real-time quantitative polymerase chain reaction (RT-qPCR). Results: In total, 548 DEGs were identified in the GSE56815 dataset. The weighted gene co-expression network analysis(WGCNA) identified 2291 key module genes, and 91 DE-MRG were obtained by combining the two. The PPI network revealed that the target gene for AKT1 interacted with most proteins. Three MRG (NELFB, SFSWAP, and MAP3K3) were identified as hub genes, with areas under the curve (AUC) 0.75, 0.71, and 0.70, respectively. The nomogram model has high diagnostic value. GO and KEGG analysis showed that ribosome pathway and cellular ribosome pathway may be the pathways regulating the progression of OP. IPA showed that MAP3K3 was associated with six pathways, including GNRH Signaling. The ssGSEA indicated that NELFB was highly correlated with iDCs (cor = -0.390, p < 0.001). The regulatory network showed a complex relationship between miRNA, transcription factor(TF) and hub genes. In addition, 4 drugs such as vinclozolin were predicted to be potential therapeutic drugs for OP. In RT-qPCR verification, the hub gene NELFB was consistent with the results of bioinformatics analysis. Conclusion: Mitophagy plays an important role in the development of osteoporosis. The identification of three mitophagy-related genes may contribute to the early diagnosis, mechanism research and treatment of OP., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Su, Yu, Li, Lu, Ren, Xu, Yang, Zhang, Ma and Li.)

Background: CD27 is an immunological checkpoint gene, plays a critical function inInhibition or activation of cancer immunity. The CD27 / CD27L axis is its pathway of action. Therefore, our goal was to examine the predictive role of CD27 in the clinical prognosis of 33 cancer types and its functions in cancer progression, as well as explore the link between pan-cancer CD27 gene expression and immune infiltration. Methods: By comprehensive use of datasets and methods from TCGA, cBioPortal, GTEx, HPA, KM-plotter, Spearman, CellMinerTM, R packages and RT-qPCR, we delved deeper into the potential impact of the CD27 on cancer development. These include expression differences, immune infiltration, matrix infiltration, gene mutations, DNA methylation, signaling pathways, TMB, MSI, and prognosis. Also, we explored CD27 interactions with different drugs. Results: The results showed that, mutated CD27 was highly expressed in most cancers. The CD27 showed strong diagnostic value in 4 cancers and marked a positive prognosis for CESC, intracervical adenocarcinoma, HNSC, and endometrial cancer, and a poor prognosis for UVM. In addition, CD27 affects multiple immune and inflammatory signaling pathways and is positively correlated with immune cell infiltration, T cell differentiation, macrophage M1 polarization, stromal infiltration, and drug sensitivity. DNA methylation is involved in CD27 expression in cancer. Conclusion: CD27, which is mutated in cancers and appears widely highly expressed and altered tumor immune invasion and stromal invasion by affecting multiple immune-related and inflammation signaling pathways, plays a significant role in CESC, HNSC, UCEC and UVM, and may be used as a therapeutic target for related cancers., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Magnetoencephalography (MEG) is a non-invasive technique that can precisely capture the dynamic spatiotemporal patterns of the brain by measuring the magnetic fields arising from neuronal activity along the order of milliseconds. Observations of brain dynamics have been used in cognitive neuroscience, the diagnosis of neurological diseases, and the brain-computer interface (BCI). In this study, we outline the basic principle, signal processing, and source localization of MEG, and describe its clinical applications for cognitive assessment, the diagnoses of neurological diseases and mental disorders, preoperative evaluation, and the BCI. This review not only provides an overall perspective of MEG, ranging from practical techniques to clinical applications, but also enhances the prevalent understanding of neural mechanisms. The use of MEG is expected to lead to significant breakthroughs in neuroscience., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Spinal cord injury (SCI) is a serious problem in the central nervous system resulting in high disability and mortality with complex pathophysiological mechanisms. Oxidative stress is one of the main secondary reactions of SCI, and its main pathophysiological marker is the production of excess reactive oxygen species. The overproduction of reactive oxygen species and insufficient antioxidant capacity lead to the occurrence of oxidative stress and neuroinflammation, and the dysregulation of oxidative stress and neuroinflammation leads to further aggravation of damage. Oxidative stress can initiate a variety of inflammatory and apoptotic pathways, and targeted antioxidant therapy can greatly reduce oxidative stress and reduce neuroinflammation, which has a certain positive effect on rehabilitation and prognosis in SCI. This article reviewed the research on different types of antioxidants and related treatments in SCI, focusing on the mechanisms of oxidative stress., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Antiviral responses are often accompanied by translation inhibition and formation of stress granules (SGs) in infected cells. However, the triggers for these processes and their role during infection remain subjects of active investigation. Copy-back viral genomes (cbVGs) are the primary inducers of the mitochondrial antiviral signaling (MAVS) pathway and antiviral immunity during Sendai virus (SeV) and respiratory syncytial virus (RSV) infections. The relationship between cbVGs and cellular stress during viral infections is unknown. Here, we show that SGs form during infections containing high levels of cbVGs, and not during infections with low levels of cbVGs. Moreover, using RNA fluorescent in situ hybridization to differentiate accumulation of standard viral genomes from cbVGs at a single-cell level during infection, we show that SGs form exclusively in cells that accumulate high levels of cbVGs. Protein kinase R (PKR) activation is increased during high cbVG infections and, as expected, is necessary for virus-induced SGs. However, SGs form independent of MAVS signaling, demonstrating that cbVGs induce antiviral immunity and SG formation through 2 independent mechanisms. Furthermore, we show that translation inhibition and SG formation do not affect the overall expression of interferon and interferon stimulated genes during infection, making the stress response dispensable for global antiviral immunity. Using live-cell imaging, we show that SG formation is highly dynamic and correlates with a drastic reduction of viral protein expression even in cells infected for several days. Through analysis of active protein translation at a single-cell level, we show that infected cells that form SGs show inhibition of protein translation. Together, our data reveal a new cbVG-driven mechanism of viral interference where cbVGs induce PKR-mediated translation inhibition and SG formation, leading to a reduction in viral protein expression without altering overall antiviral immunity., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 González Aparicio et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

As a filamentous pathogenic fungus with high-yield of aflatoxin B 1 , Aspergillus flavus is commonly found in various agricultural products. It is crucial to develop effective strategies aimed at the prevention of the contamination of A. flavus and aflatoxin. Hexokinase AfHxk1 is a critical enzyme in fungal glucose metabolism. However, the role of AfHxk1 in A. flavus development, aflatoxin biosynthesis, and virulence has not yet been explored. In this study, afHxk1 gene deletion mutant (Δ afHxk1 ), complementary strain (Com- afHxk1 ), and the domain deletion strains ( afHxk1 ΔD1 and afHxk1 ΔD2 ) were constructed by homologous recombination. Phenotype study and RT-qPCR revealed that AfHxk1 upregulates mycelium growth and spore and sclerotia formation, but downregulates AFB 1 biosynthesis through related classical signaling pathways. Invading models and environmental stress analysis revealed that through involvement in carbon source utilization, conidia germination, and the sensitivity response of A. flavus to a series of environmental stresses, AfHxk1 deeply participates in the regulation of pathogenicity of A. flavus to crop kernels and Galleria mellonella larvae. The construction of domain deletion strains, afHxk1 ΔD1 and afHxk1 ΔD2 , further revealed that AfHxk1 regulates the morphogenesis, mycotoxin biosynthesis, and the fungal pathogenicity mainly through its domain, Hexokinase&#95;2. The results of this study revealed the biological role of AfHxk1 in Aspergillus spp., and might provide a novel potential target for the early control of the contamination of A. flavus .

Cognitive impairment is a multifactorial and multi-step pathological process that places a heavy burden on patients and the society. Neuroinflammation is one of the main factors leading to cognitive impairment. The inflammasomes are multi-protein complexes that respond to various microorganisms and endogenous danger signals, helping to initiate innate protective responses in inflammatory diseases. NLRP3 inflammasomes produce proinflammatory cytokines (interleukin IL-1β and IL-18) by activating caspase-1. In this review, we comprehensively describe the structure and functions of the NLRP3 inflammasome. We also explore the intrinsic relationship between the NLRP3 inflammasome and cognitive impairment, which involves immune cell activation, cell apoptosis, oxidative stress, mitochondrial autophagy, and neuroinflammation. Finally, we describe NLRP3 inflammasome antagonists as targeted therapies to improve cognitive impairment., (© 2023. The Author(s).)

As a widely distributed food-borne pathogenic fungus, Aspergillus flavus and its secondary metabolites, mainly aflatoxin B1 (AFB 1 ), pose a great danger to humans. It is urgent to reveal the complex regulatory network of toxigenic and virulence of this fungus. The bio-function of Set9, a SET-domain-containing histone methyltransferase, is still unknown in A. flavus. By genetic engineering means, this study revealed that, through catalyzing H4K20me2 and -me3, Set9 is involved in fungal growth, reproduction, and mycotoxin production via the orthodox regulation pathway, and regulates fungal colonization on crop kernels through adjusting fungal sensitivity reactions to oxidation stress and cell wall integrity stress. Further domain deletion and point mutation inferred that the SET domain is the core element in catalyzing H4K20 methylation, and D200 site of the domain is the key amino acid in the active center of the methyltransferase. Combined with RNA-seq analysis, this study revealed that Set9 regulates the aflatoxin gene cluster by the AflR-like protein (ALP), other than traditional AflR. This study revealed the epigenetic regulation mechanism of fungal morphogenesis, secondary metabolism, and pathogenicity of A. flavus mediated by the H4K20-methyltransferase Set9, which might provide a potential new target for early prevention of contamination of A. flavus and its deadly mycotoxins., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Biofouling is a major challenge limiting the practical application of biofiltration-facilitated gravity-driven membrane (GDM) systems in drinking water treatment. In this study, ultraviolet irradiation, including ultraviolet (UV) and vacuum ultraviolet (VUV) irradiation, was used for in-situ purification of membrane tanks to control membrane biofouling. After using UV and VUV, the permeate flux increased significantly by 26.1% and 78.3%, respectively, which was mainly due to the decreased cake layer resistance (R c ). The permeability of the biofouling layer improved after UV and VUV application, as evidenced by the increased surface porosity and decreased thickness. The contents of loosely bound extracellular proteins (LB-PN) and tightly bound extracellular proteins (TB-PN) in the biofouling layer were reduced after UV and VUV irradiation. The decreased LB-PN and TB-PN improved the interfacial free energy between the fouling itself and between the fouling and the membrane, which contributed to the reduction of interfacial cohesion and adhesion, resulting in a looser and thinner biofouling layer and a cleaner membrane. The concentration of protein-like material in the membrane tank decreased after UV and VUV irradiation, significantly altering the bacterial community structure on the membrane surface (Mantel's r > 0.7, p < 0.05). The changes in the metabolic state were responsible for the differences in the LB-PN and TB-PN contents. The inhibition of "Alanine, aspartate and glutamate metabolism" and "Glycine, serine and threonine metabolism" reduced amino acid biosynthesis, which restricted the secretion of LB-PN and TB-PN. Critical genera in the Proteobacteria phylum, such as Hirschia, Rhodobacter, Nordella, Candidatus&#95;Berkiella, and Limnohabitans, were involved in metabolite transformation. Overall, the in-situ application of UV and VUV can be an effective alternative strategy to mitigate membrane biofouling, which would facilitate the practical application of biofiltration-facilitated GDM systems in drinking water treatment., Competing Interests: Declaration of Competing Interest The authors declared that they have no conflicts of interest to this paper. We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the paper submitted., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Oxidative stress plays a crucial role in the pathogenesis of hepatic encephalopathy (HE), but the mechanism remains unclear. GABAergic neurons in substantia nigra pars reticulata (SNr) contribute to the motor deficit of HE. The present study aims to investigate the effects of oxidative stress on HE in male mice. The results validate the existence of oxidative stress in both liver and SNr across two murine models of HE induced by thioacetamide (TAA) and bile duct ligation (BDL). Systemic mitochondria-targeted antioxidative drug mitoquinone (Mito-Q) rescues mitochondrial dysfunction and oxidative injury in SNr, so as to restore the locomotor impairment in TAA and BDL mice. Furthermore, the GAD2-expressing SNr population (SNr GAD2 ) is activated by HE. Both overexpression of mitochondrial uncoupling protein 2 (UCP2) targeted to SNr GAD2 and SNr GAD2 -targeted chemogenetic inhibition targeted to SNr GAD2 rescue mitochondrial dysfunction in TAA-induced HE. These results define the key role of oxidative stress in the pathogenesis of HE., (© 2023. The Author(s).)

Aqueous zinc ion batteries (ZIBs) are promising energy storage devices due to the advantageous features of Zn. However, developing suitable cathode materials with high performance is still an urgent task for the development of ZIBs. In this work, we report on the preparation of a flexible cathode for ZIBs consisting of carbon fiber supported MnMoO 4 nanostructures protected with N-doped carbon coatings (CF/MnMoO4@NCs). The N-doped carbon coating on MnMoO 4 nanostructures can buffer volume expansion of MnMoO 4 , and the CF and NCs with good electronic conductivity can facilitate quick electrons transportation in the CF/MnMoO 4 @NCs system. The optimized CF/MnMoO 4 @NCs cathode exhibits high capacity and good rate capability. Specifically, it delivers an outstanding discharge capacity of 663 mA h g -1 at a current density of 0.1 A/g after 100 cycles, and at a current density of 2 A/g, the cathode can still achieve a discharge capacity of 212 mA h g -1 . This work expands the choice of cathode material and provides constructive direction on designing high-performance cathode materials for ZIBs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Periodontitis is an inflammatory disease initiated by periodontopathogenic bacteria in the dental plaque biofilms. Understanding the role of Porphyromonas gingivalis ( P. gingivalis ), a keystone pathogen associated with chronic periodontitis, in the inflammatory response is crucial. Herein, we investigated whether P. gingivalis infection triggers the expression of the type I IFN gene and various cytokines and leads to activation of the cGAMP synthase-stimulator of IFN genes (cGAS-STING) pathway both in vitro and in a mouse model. Additionally, in an experimental model of periodontitis using P. gingivalis , Sting Gt mice showed lower levels of inflammatory cytokines and bone resorption than wild-type mice. Furthermore, we report that a STING inhibitor (SN-011) significantly decreased inflammatory cytokine production and osteoclast formation in a periodontitis mouse model with P. gingivalis . In addition, STING agonist (SR-717) -treated periodontitis mice displayed enhanced macrophage infiltration and M1 macrophage polarization in periodontal lesions compared with that in vehicle-treated periodontitis mice. In conclusion, our results demonstrate that the cGAS-STING signaling pathway may be one of the key mechanisms crucial for the P. gingivalis -induced inflammatory response that leads to chronic periodontitis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Bi, Yang, Liao, Ji, Ma, Cai, Li, Yang, Sun, Liang and Shi.)

Objective: To explore the related risk factors of serous exudation after antibiotic-loaded calcium sulfate treatment of fracture-related infections and to provide a theoretical basis for clinical treatment and prevention of serous exudation complications. Methods: The clinical data of 145 patients with limb fracture-related infection treated with antibiotic-loaded calcium sulfate in Xi'an Honghui Hospital from January 2019 to December 2022 were retrospectively analyzed. All patients were diagnosed with fracture-related infection by preoperative magnetic resonance examination, bacterial culture and gene detection and received antibiotic-loaded calcium sulfate implantation. The postoperative serous exudation was recorded through hospitalization observation, outpatient review or follow-up. The collected clinical data were sorted out, and the patient data were divided into serous exudation groups and non-exudation groups. Firstly, the clinical data of the two groups were compared by single-factor analysis to screen out the risk factors. Then multivariate binary Logistic regression analysis determined the independent risk factors and protective factors. Results: 1) According to the inclusion and exclusion criteria, there were 145 cases with complete clinical data, including 27 cases in the non-infectious exudation group and 118 cases in the non-exudative group; 2) Univariate analysis showed that the history of diabetes, smoking history, calcium sulfate implantation, drainage time, combined flap surgery, geometric shape of implanted calcium sulfate, and thickness of soft tissue covered by the surgical area were all associated with the occurrence of non-infectious exudation after antibiotic-loaded calcium sulfate implantation ( p < 0.05); 3) The amount of implanted calcium sulfate was more [OR = 5.310, (1.302-21.657), p = 0.020], combined with flap surgery [OR = 3.565, (1.195-10.641), p = 0.023], and the thickness of soft tissue coverage in the operation area was thinner [OR = 5.305, (1.336-21.057), p = 0.018]. Longer drainage time [OR = 0.210, (0.045-0.967), p = 0.045] was a protective factor for non-infectious exudation after antibiotic-loaded calcium sulfate implantation. Conclusion: 1) The probability of serous exudation in patients with fracture-associated infection after antibiotic-loaded calcium sulfate surgery was 18.62%. This complication may cause a heavier economic and psychological burden on patients; 2) With the increase of bone infection area and the application of more calcium sulfate, the incidence of serous exudation after antibiotic-loaded calcium sulfate surgery in patients with the fracture-related infection will increase, so we should use the amount of calcium sulfate reasonably on the premise of sufficient control of infection in clinical work, and the incidence of serous exudation will also increase due to the recent skin flap surgery and the thinner soft tissue coverage of calcium sulfate implantation area; 3) Under the premise of being able to drain the drainage from the surgical area, the longer drainage time of the drainage tube has a positive effect on preventing the occurrence of serous exudation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Du, Su, Li, Ji, Lu, Xu, Yang, Zhang, Li and Ma.)

Purpose: There are few studies on the risk factors of postoperative complications after surgical treatment of hepatic hemangioma (HH). This study aims to provide a more scientific reference for clinical treatment., Methods: The clinical characteristics and operation data of HH patients undergoing surgical treatment in the First Affiliated Hospital of Air Force Medical University from January 2011 to December 2020 were retrospectively collected. All enrolled patients were divided into two groups based on the modified Clavien-Dindo classification: Major group (Grade II/III/IV/V) and Minor group (Grade I and no complications). Univariate and multivariate regression analysis was used to explore the risk factors for massive intraoperative blood loss (IBL) and postoperative Grade II and above complications., Results: A total of 596 patients were enrolled, with a median age of 46.0 years (range, 22-75 years). Patients with Grade II/III/IV/V complications were included in the Major group (n = 119, 20%), and patients with Grade I and no complications were included in the Minor group (n = 477, 80%). The results of multivariate analysis of Grade II/III/IV/V complications showed that operative duration, IBL, and tumor size increased the risk of Grade II/III/IV/V complications. Conversely, serum creatinine (sCRE) decreased the risk. The results of multivariate analysis of IBL showed that tumor size, surgical method, and operative duration increased the risk of IBL., Conclusions: Operative duration, IBL, tumor size, and surgical method are independent risk factors that should be paid attention to in HH surgery. In addition, as an independent protective factor for HH surgery, sCRE should attract more attention from scholars., (© 2023. The Author(s).)

The physicochemical properties of powdered activated carbon (PAC) are important factors affecting its adsorption performance, which is also related to the characteristics of target organic pollutants. In this study, the key indicators affecting the adsorption performance of PAC were identified, and the physicochemical properties of PACs were modified by hydrogen peroxide and/or ultrasound in a targeted manner to improve the adsorption performance. The results indicated the adsorption properties of printing and dyeing secondary effluent organic matter (EfOM) in terms of COD cr and UV absorbance at 254 nm (UV 254 ) positively correlated with mesoporous volume, average pore size and acid group content of PAC. After modification, the mesoporous volume and average pore size of PAC increased, and the number of acidic groups increased, thus enhancing the adsorption efficiency. EfOM removal characteristics showed that PAC preferentially adsorbed unsaturated bonds or aromatic compounds, tryptophan-like proteins, soluble microbial metabolites and low molecular weight fractions below 1 kDa. In addition, the relative contents of specific surface area, pore volume and oxygen-containing functional groups (O-CO, C-OH, CO/O-C-O) of PAC decreased after adsorption, indicating that EfOM adsorption was a physical and chemical process, including pore filling, hydrophobic interaction and chemical bond force interaction. In general, PACs with larger mesoporous volume, average pore size and abundant acid groups possessed good adsorption performance towards EfOM., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: To understand the status and related factors of overweight and obesity in children and adolescents aged 6-17 in Yunnan Province., Methods: From 2016 to 2017, 3463 children and adolescents aged 6-17 from 65 primary and secondary schools in 13 counties of Yunnan Province were selected by stratified cluster sampling method for face-to-face questionnaire survey, including 1716 boys and 1747 girls, 2098 elementary school students, 762 middle school students, 603 high school students, of which, 1368 students from urban area and 2095 students from rural area. The questionnaire included information including, weekly consumption of sugary drinks, sweets, puffed food, fruits, vegetables, breakfast, daily activities of moderate or high intensity, school sports, daily hours of playing video games and watching TV, daily sleep and outdoor activities. Height and weight were measured using standard method. SPSS20.0 was used for χ~(2 )test and multivariate Logistic regression analysis., Results: The prevalence of overweight and obesity among children and adolescents aged 6-17 were 8.43%(292/3463) and 6.01%(208/3463) respectively. The overweight rates of male students and female students were 8.45%(145/1716) and 8.41%(147/1747) respectively, and the statistic was significant differently(χ~(2 )=0.001, P&gt;0.05). The overweight rates of urban and rural children and adolescents were 11.99%(164/1368) and 6.11%(128/2095) respectively, and the statistic was significant differently(χ~2=37.04, P&lt;0.01). The overweight rates of primary school, middle school and high school were 7.53%(158/2098), 9.32%(71/762) and 10.45%(63/603) respectively, and the statistic was significant differently(χ~2=6.15, P&lt;0.05). The obesity rates of male and female students were 7.11%(122/1716) and 4.92%(86/1747) respectively, and the statistic was significant differently(χ~2=7.33, P&lt;0.01). The obesity rates of urban and rural children and adolescents were 9.50%(130/1368) and 3.72%(78/2095) respectively, and the statistic was significant differently(χ~2=48.97, P&lt;0.01). The obesity rates of primary school, middle school and high school were 7.67%(161/2098), 3.15%(24/762) and 3.81%(23/603), respectively, and the statistic was significant differently(χ~2=26.48, P&lt;0.01). Multivariate Logistic regression analysis showed that cities(OR=2.025, 95%CI 1.646-2.492) and non-residential schools(OR=1.808, 95%CI 1.470-2.223) were associated with overweight and obesity in children and adolescents, both of which were statistically significant(P&lt;0.05)., Conclusion: The prevalence of overweight and obesity among children and adolescents aged 6-17 in Yunnan Province were high. Urban, non-residential school children and adolescents are more likely to be overweight and obesity.

Objective: Postoperative delirium is common after general anesthesia in older patients. However, there are currently no effective preventive measures. This study investigated the effect of repeated intranasal administration of different insulin doses before surgery on postoperative delirium in older patients with esophageal cancer, and the possible mechanism for its efficacy., Methods: In this randomized, placebo-controlled, double-blind, parallel-group study, 90 older patients were randomly assigned to either a Control (normal saline), Insulin 1 (20 U/0.5 mL intranasal insulin), or Insulin 2 (30 U/0.75 mL intranasal insulin) group. Delirium was assessed on postoperative days 1 (T2), 2 (T3), and 3 (T4) using the Confusion Assessment Method for the Intensive Care Unit. Serum τ and Aβ protein levels were measured at T0 (before insulin/saline administration), T1 (end of surgery), T2, T3 and T4., Results: The Insulin 2 group had a significantly lower prevalence of delirium compared to the Control and Insulin 1 groups three days after surgery. Compared to baseline, τ and Aβ protein levels increased significantly at T1-T4. Compared to the Control group, the Insulin 1 and 2 groups had significantly lower τ and Aβ protein levels at T1-T4, and the Insulin 2 group had significantly lower levels than the Insulin 1 group at T1-T2., Conclusion: The administration of 30 U of intranasal insulin twice daily, from 2 days preoperatively until 10 minutes preanesthesia on the day of surgery, can significantly reduce postoperative delirium in older patients undergoing radical esophagectomy. It can also decrease postoperative τ and Aβ protein expression without causing hypoglycemia., Clinical Trial Registration: This study was registered at the Chinese Clinical Trial Registry (www.chictr.org.cn, with the unique identifier: ChiCTR2100054245; December 11, 2021)., Competing Interests: The authors certify that there are no conflicts of interest with any financial organization regarding the material discussed in the manuscript., (© 2023 Huang et al.)

Surfactants are increasingly used in systems that come into contact with the human body, such as food, pharmaceuticals, cosmetics and personal hygiene products. Increasing attention is being devoted to the toxic effects of surfactants in various human contact formulations, as well as the removal of residual surfactants. In the presence of ozone (O 3 ), anion surfactants-a characteristic micro-pollutant-such as sodium dodecylbenzene sulfonate (SDBS) in greywater, can be removed using radical advanced oxidation. Herein, we report a systematic study of the SDBS degradation effect of O 3 activated by vacuum ultraviolet (VUV) irradiation and the influence of water composition on VUV/O 3 , and determined the contribution of radical species. We show a synergistic effect of VUV and O 3 , while VUV/O 3 reached a higher mineralization (50.37%) than that of VUV (10.63%) and O 3 (29.60%) alone. The main reactive radicals of VUV/O 3 were HO•. VUV/O 3 had an optimal pH of 9. The addition of SO 4 2- had almost no effect on the degradation of SDBS by VUV/O 3 , Cl - and HCO 3 - slightly reduced the reaction rate, and NO 3 - had a significant inhibition on the degradation. In total, SDBS had three isomers, with which the three degradation pathways were very comparable. Compared with SDBS, the toxicity and harmfulness of the degradation by-products of the VUV/O 3 process decreased. Additionally, VUV/O 3 could degrade synthetic anion surfactants from laundry greywater effectively. Overall, the results show the potential of VUV/O 3 in safeguarding humans from residual surfactant hazards.

Leigh syndrome (LS)/Leigh-like syndrome (LLS) is one of the most common mitochondrial disease subtypes, caused by mutations in either the nuclear or mitochondrial genomes. Here, we identified a novel intronic mutation (c.82-2 A > G) and a novel exonic insertion mutation (c.290dupT) in TMEM126B from a Chinese patient with clinical manifestations of LLS. In silico predictions, minigene splicing assays and patients' RNA analyses determined that the c.82-2 A > G mutation resulted in complete exon 2 skipping, and the c.290dupT mutation provoked partial and complete exon 3 skipping, leading to translational frameshifts and premature termination. Functional analysis revealed the impaired mitochondrial function in patient-derived lymphocytes due to severe complex I content and assembly defect. Altogether, this is the first report of LLS in a patient carrying mutations in TMEM126B. Our data uncovers the functional effect and the molecular mechanism of the pathogenic variants c.82-2 A > G and c.290dupT, which expands the gene mutation spectrum of LLS and clinical spectrum caused by TMEM126B mutations, and thus help to clinical diagnosis of TMEM126B mutation-related mitochondrial diseases., (© 2022. The Author(s).)

The oxygen evolution reaction (OER) is the performance-limiting step in the process of water splitting. In situ electrochemical conditioning could induce surface reconstruction of various OER electrocatalysts, forming reactive sites dynamically but at the expense of fast cation leaching. Therefore, achieving simultaneous improvement in catalytic activity and stability remains a significant challenge. Herein, we used a scalable cation deficiency-driven exsolution approach to ex situ reconstruct a homogeneous-doped cobaltate precursor into an Ir/CoO/perovskite heterojunction (SCI-350), which served as an active and stable OER electrode. The SCI-350 catalyst exhibited a low overpotential of 240 mV at 10 mA cm -2 in 1 M KOH and superior durability in practical electrolysis for over 150 h. The outstanding activity is preliminarily attributed to the exponentially enlarged electrochemical surface area for charge accumulation, increasing from 3.3 to 175.5 mF cm -2 . Moreover, density functional theory calculations combined with advanced spectroscopy and 18 O isotope-labeling experiments evidenced the tripled oxygen exchange kinetics, strengthened metal-oxygen hybridization, and engaged lattice oxygen oxidation for O-O coupling on SCI-350. This work presents a promising and feasible strategy for constructing highly active oxide OER electrocatalysts without sacrificing durability., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

The present study aimed to explore the clinical efficacy of laparoscopic partial splenectomy in the treatment of benign lesions of the spleen and partial splenic rupture. The clinical value of laparoscopic partial splenectomies performed between March 2015 and May 2022 was retrospectively analyzed. Cases considered included the following: 14 spleen cysts, five spleen hemangiomas, one spleen hamartoma and two splenic ruptures. Lesion diameters of cases ranged from 5.0-11.3 cm. Results indicated that all 22 patients had an uneventful surgery, including 11 cases with lesions located in the upper pole of the spleen, nine in the lower pole of the spleen, one in the upper middle pole and one in the middle and lower pole. Operation time ranged from 75-180 min (mean: 120±17 min) and intraoperative bleeding ranged from 80-300 ml (mean: 178±70 ml). The average duration of postoperative hospitalization was 6±2 days, with all patients followed up for 10-12 months. Patients reported no symptoms of discomfort and had platelet levels within normal range. In conclusion, laparoscopic partial splenectomy allows for lesion resection while retaining normal splenic function and may be effectively used for treating benign spleen tumors and partial splenic rupture. However, the operation is difficult and surgeons must be able to perform minimally invasive techniques and strictly screen cases., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Xing et al.)

Objective: Delirium is a common postoperative complication in elderly patients with intertrochanteric femur fracture. This study aimed at analyzing risk factors for postoperative delirium (POD) in patients after proximal femoral nail anti-rotation (PFNA)., Methods: From February 2017 to February 2021, we included elderly patients with intertrochanteric fractures who underwent PFNA. The predictive ability and cut-off value of neutrophil/lymphocyte ratio (NLR) for POD were evaluated using receiver operating characteristic (ROC) curve. Univariate and multivariate analyses were used to investigate the association between NLR and POD., Results: We enrolled 315 patients. The ROC curve suggested that NLR ≥ 4.85 was the optimal cut-off value for POD. The POD and non-POD groups differed significantly in age, diabetes, time from injury to operation, preoperative albumin level, neutrophil count, and NLR (P < 0.05). Logistic regression indicated that NLR ≥ 4.85 (odds ratio [OR] = 3.491; 95% confidence interval [CI]: 1.731-5.982; P < 0.001), old age (OR = 1.921; 95% CI: 1.267-4.125; P < 0.001), time from injury to operation ≥ 48 h (OR = 1.733; 95% CI: 1.212-3.542; P = 0.007), and preoperative albumin level ≤ 35 g/L (OR = 2.274; 95% CI: 1.662-4.846; P = 0.001) increased the risk of POD., Conclusion: Old age, time from injury to operation ≥ 48 h, preoperative albumin level ≤ 35 g/L, and NLR ≥ 4.85 were independent risk factors for POD. Thus, NLR may predict POD in elderly patients with intertrochanteric femur fractures after PFNA., Competing Interests: None., (AJTR Copyright © 2023.)

In vivo multiplexed bioimaging in the second near-infrared window (NIR-II, 1000-1700 nm), owing to its superiorities of simultaneous multi-channel (multicolor) observations for multiple intrinsic biomarkers, high sensitivity, deeper penetration and high spatiotemporal resolution, and high throughput, has been a growing technology in fundamental medical diagnosis and clinical applications. Among several NIR-II nanoprobes for multiplexed bioimaging, the inorganic nanoprobes based on quantum dots (QDs) and lanthanide downconversion nanoparticles (DCNPs), as well as organic fluorophores based on donor-acceptor-donor (D-A-D) chromophores, polymethine dyes, and lanthanide complexes are extensively suitable for intravital imaging and diagnosis of disease, exhibiting excellent accomplishments. Here, we summarize recent advances in NIR-II-emitted nanoprobes for intravital multiplexed bioimaging. Furthermore, the current challenges and potential opportunities in designing novel long-wavelength nanoprobes for deep-tissue intravital multiplexed bioimaging are discussed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: CblC deficiency, the most common cobalamin metabolic abnormality, is caused by pathogenic variants in the MMACHC gene. The renal complications of this disease have been described only in a small number of cases. This study aimed to better delineate renal phenotype and genetic characteristics in Chinese children with cblC defect., Methods: Children with cblC deficiency who manifested as kidney damage were enrolled. Clinical, renal pathological, and genetic data were reviewed in detail., Results: Seven cases were enrolled. Ages at disease onset ranged from 9 months to 5 years. All patients presented with hematuria and proteinuria, and 2/7 cases presented with nephrotic syndrome. Renal dysfunction was observed in 4/7 cases. Renal biopsy was performed in 5/7 cases, and all of them had renal thrombotic microangiopathy. Macrocytic anemia was detected in all seven patients. Six out of seven cases had hypertension, and 2/7 cases presented with pulmonary hypertension. Two of them had a mild intellectual disability, and one suffered from epilepsy. Increased urine methylmalonic acid and plasma homocysteine were detected in seven cases, while two patients had normal levels of urine methylmalonic acid at the initial evaluation. After diagnosis, all seven cases were treated with hydroxocobalamin IM. Six cases were followed-up for 3-8 years. After treatments, anemia was the first to be recovered, followed by proteinuria. Renal function recovered after 1 year in two cases, whereas patient 2 progressed to stage 2 chronic kidney disease 13 years after onset. While a case presented with end-stage kidney disease because of late diagnosis, one case died 3 months after disease onset due to giving up treatment. Three MMACHC pathogenic variants c.80A > G (8/14), c.609G > A (4/14), and c.658&#95;660delAAG (2/14) were detected in all seven children., Conclusion: MMACHC variant c.80A > G may be associated with prominent renal complications in Chinese cblC patients. Macrocytic anemia and hyperhomocysteinemia are useful clues for patients with hematuria and proteinuria caused by cblC defect. The most frequent renal pathological manifestation is thrombotic microangiopathy. Early diagnosis and treatment resulted in improving renal and hematological signs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Liu, Xiao, Yao, Wang, Zhang, Zhong, Yang, Ding and Wang.)