Relative frequencies and clinical features of Guillain-Barré Syndrome before and during the COVID-19 pandemic in North China.

OBJECTIVE: Most studies investigated the relationship between COVID-19 and Guillain-Barré syndrome (GBS) by comparing the incidence of GBS before and during the pandemic of COVID-19. However, the findings were inconsistent, probably owing to varying degrees of the lockdown policy. The quarantine requirements and travel restrictions in China were lifted around December 7, 2022. This study aimed to explore whether the relative frequency of GBS increased during the major outbreak in the absence of COVID-19-mandated social restrictions in China. METHODS: GBS patients admitted to the First Hospital, Shanxi Medical University, from December 7, 2022 to February 20, 2023, and from June, 2017 to August, 2019 were included. The relative frequencies of GBS in hospitalized patients during different periods were compared. The patients with and without SARS-CoV-2 infection within six weeks prior to GBS onset formed the COVID-GBS group and non-COVID-GBS group, respectively. RESULTS: The relative frequency of GBS among hospitalized patients during the major outbreak of COVID-19 (13/14,408) was significantly higher than that before the COVID-19 epidemic (29/160,669, P < 0.001). More COVID-GBS patients (11/13) presented AIDP subtype than non-COVID-GBS cases (10/27, P = 0.003). The mean interval between onset of infective symptoms and GBS was longer in COVID-GBS (21.54 ± 11.56 days) than in non-COVID-GBS (5.76 ± 3.18 days, P < 0.001). CONCLUSIONS: COVID-19 significantly increased the incidence of GBS. Most COVID-GBS patients fell into the category of AIDP, responded well to IVIg, and had a favorable prognosis.

The impact of maternal intrahepatic cholestasis during pregnancy on the growth trajectory of offspring: a population-based nested case‒control cohort study.

BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is associated with an increased risk of adverse fetal outcomes, yet its influence on offspring growth remains unclear. Our study dynamically tracks growth rates in children from ICP and healthy mothers and investigates the link between maternal liver function and developmental abnormalities in offspring. METHOD: Our case‒control study involved 97 women with ICP and 152 with uncomplicated pregnancies nested in a cohort of their offspring, including 50 from the ICP group and 87 from the uncomplicated pregnancy group. We collected pediatric growth and development data, with a maximum follow-up duration of 36 months. Stratified analyses of children's height, weight, and head circumference were conducted, and Spearman's rank correlation was applied to examine the relationships between maternal serological markers and pediatric growth metrics. RESULT: Maternal liver and renal functions, along with serum lipid profiles, significantly differed between the ICP and normal groups. In the ICP group, the offspring showed elevated alanine aminotransferase (ALT), direct bilirubin (DBIT), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B (APOB) levels. Notably, the length-for-age z score (LAZ), weight-for-age z score (WAZ), and head circumference-for-age z score (HCZ) were lower in ICP offspring compared with those from normal pregnancies within the 1- to 12-month age range (P < 0.05). However, no significant differences in LAZ, weight-for-length z score (WLZ), BMI-for-age z score (BAZ), or HCZ were observed between groups in the 13- to 36-month age range. Maternal maximum lactate dehydrogenase (LDH) and total bile acids (TBA) levels during pregnancy were inversely correlated with LAZ and WAZ in the first year. Furthermore, offspring of mothers with ICP exhibited a greater incidence of stunting (24% vs. 6.9%, P = 0.004) and abnormal HCZ (14% vs. 3.7%, P = 0.034). CONCLUSIONS: Growth disparities in offspring of ICP-affected pregnancies were most significant within the 1- to 12-month age range. During this period, maximum maternal LDH and TBA levels were negatively correlated with LAZ and WAZ values of offspring. The observation of similar growth rates between ICP and control group offspring from 13 to 36 months suggested catch-up growth in the ICP group.

FSIP2 plays a role in the acrosome development during spermiogenesis.

BACKGROUND: Loss-of-function mutations in FSIP2 result in multiple morphological abnormalities of the flagella in humans and mice. Intriguingly, a recent study found that FSIP2 might regulate the expression of acrosomal proteins, indicating that Fsip2 might be involved in acrosome development in mice. However, whether FSIP2 also function in acrosome biogenesis in humans is largely unknown, and the underlying mechanism of which is unexplored. OBJECTIVE: Our objective was to reveal potential function of FSIP2 in regulating sperm acrosome formation. METHODS: We performed whole exome sequencing on four asthenoteratozoospermic patients. Western blot analysis and immunofluorescence staining were conducted to assess the protein expression of FSIP2. Proteomics approach, liquid chromatography-tandem mass spectrometry and co-immunoprecipitation were implemented to clarify the molecules in acrosome biogenesis regulated by FSIP2. RESULTS: Biallelic FSIP2 variants were identified in four asthenoteratozoospermic individuals. The protein expression of MUT-FSIP2 was sharply decreased or absent in vitro or in vivo. Interestingly, aside from the sperm flagellar defects, the acrosomal hypoplasia was detected in numerous sperm from the four patients. FSIP2 co-localised with peanut agglutinin in the acrosome during spermatogenesis. Moreover, FSIP2 interacted with proteins (DPY19L2, SPACA1, HSP90B1, KIAA1210, HSPA2 and CLTC) involved in acrosome biogenesis. In addition, spermatozoa from patients carrying FSIP2 mutations showed downregulated expression of DPY19L2, ZPBP, SPACA1, CCDC62, CCIN, SPINK2 and CSNK2A2. CONCLUSION: Our findings unveil that FSIP2 might involve in sperm acrosome development, and consequently, its mutations might contribute to globozoospermia or acrosomal aplasia. We meanwhile first uncover the potential molecular mechanism of FSIP2 regulating acrosome biogenesis.

Grouped-seq for integrated phenotypic and transcriptomic screening of patient-derived tumor organoids.

Patient-derived tumor organoids (PDOs) have emerged as a reliable in vitro model for drug discovery. However, RNA sequencing-based analysis of PDOs treated with drugs has not been realized in a high-throughput format due to the limited quantity of organoids. Here, we translated a newly developed pooled RNA-seq methodology onto a superhydrophobic microwell array chip to realize an assay of genome-wide RNA output unified with phenotypic data (Grouped-seq). Over 10-fold reduction of sample and reagent consumption together with a new ligation-based barcode synthesis method lowers the cost to ∼$2 per RNA-seq sample. Patient-derived colorectal cancer (CRC) organoids with a number of 10 organoids per microwell were treated with four anti-CRC drugs across eight doses and analyzed by the Grouped-seq. Using a phenotype-assisted pathway enrichment analysis (PAPEA) method, the mechanism of actions of the drugs were correctly derived, illustrating the great potential of Grouped-seq for pharmacological screening with tumor organoids.

Quercetin Alleviates Pulmonary Fibrosis in Silicotic Mice by Inhibiting Macrophage Transition and TGF-ß-Smad2/3 Pathway.

Silicosis is a pulmonary disease caused by the inhalation of silica. There is a lack of early and effective prevention, diagnosis, and treatment methods, and addressing silicotic fibrosis is crucial. Quercetin, a flavonoid with anti-carcinogenic, anti-inflammatory, and antiviral properties, is known to have a suppressive effect on fibrosis. The present study aimed to determine the therapeutic effect of quercetin on silicotic mice and macrophage polarity. We found that quercetin suppressed silicosis in mice. It was observed that SiO2 activated macrophage polarity and the macrophage-to-myofibroblast transition (MMT) by transforming the growth factor-ß (TGF-ß)-Smad2/3 signaling pathway in silicotic mice and MH-S cells. Quercetin also attenuated the MMT and the TGF-ß-Smad2/3 signaling pathway in vivo and in vitro. The present study demonstrated that quercetin is a potential therapeutic agent for silicosis, which acts by regulating macrophage polarity and the MMT through the TGF-ß-Smad2/3 signaling pathway.

Tembusu Virus Nonstructural Protein 2B Antagonizes Type I Interferon Production by Targeting MAVS for Degradation.

Tembusu virus (TMUV) is a newly emerged avian flavivirus that has caused severe egg-drop syndrome and fatal encephalitis in domestic ducks. It has spread widely throughout the main duck-producing areas in Asia, resulting in substantial economic losses to the duck industry. Previous studies have reported that TMUV has evolved several strategies to counteract the duck's innate immune responses to successfully establish infection in its host cells. However, the mechanisms underlying this phenomenon have not been elucidated. Here, we discovered that TMUV-encoded NS2B is a negative regulator of poly(I:C)-induced duck interferon-ß (IFN-ß) expression. Mechanistically, TMUV NS2B was found to interact specifically with the mitochondrial antiviral-signaling protein (duMAVS). Consequently, duMAVS was degraded through the K48-linked ubiquitination and proteasomal pathway, leading to the interruption of the RIG-I-like receptor (RLR) signaling. Further analyses also identified K321, K354, K398, and K411 as crucial residues for NS2B-mediated ubiquitination and degradation of duMAVS. Additionally, we demonstrated that NS2B functions by recruiting the E3 ubiquitin ligase duck membrane-associated RING-CH-type finger 5 (duMARCH5) to modify duMAVS via polyubiquitination, blocking the duMAVS-mediated innate immune response and promoting TMUV replication. Taken together, our findings revealed a novel mechanism by which TMUV evades the duck's antiviral innate immune responses. IMPORTANCE Tembusu virus (TMUV), an emerging pathogenic flavivirus, has spread to most duck farming areas in Asia since 2010, causing significant economic losses to the duck industry. Recently, TMUV has expanded its host range and may pose a potential threat to mammals, including humans. Understanding the interaction between TMUV and its host is essential for the development of effective vaccines and therapeutics. Here, we show that NS2B encoded by TMUV inhibits IFN production by interacting with duck MAVS (duMAVS) to mediate ubiquitination and proteasomal degradation. Further studies suggest that the E3 ubiquitin ligase duck membrane-associated RING-CH-type finger 5 (duMARCH5) is recruited by NS2B to mediate proteasomal degradation of duMAVS. As a result, the innate immune response triggered by the RIG-I-like receptor (RLR) is disrupted, facilitating viral replication. Overall, our results reveal a novel mechanism by which TMUV evades host innate immunity and provide new therapeutic strategies to prevent TMUV infection.

The mechanisms of nerve injury caused by viral infection in the occurrence of gastrointestinal motility disorder-related diseases.

Gastrointestinal motility refers to the peristalsis and contractility of gastrointestinal muscles, including the force and frequency of gastrointestinal muscle contraction. Gastrointestinal motility maintains the normal digestive function of the human body and is a critical component of the physiological function of the digestive tract. At present, gastrointestinal motility disorder-related diseases are gradually affecting human production and life. In recent years, it has been consistently reported that the enteric nervous system has a coordinating and controlling role in gastrointestinal motility. Motility disorders are closely related to functional or anatomical changes in the gastrointestinal nervous system. At the same time, some viral infections, such as herpes simplex virus and varicella-zoster virus infections, can cause damage to the gastrointestinal nervous system. Therefore, this paper describes the mechanisms of viral infection in the gastrointestinal nervous system and the associated clinical manifestations. Studies have indicated that the means by which viruses can cause the infection of the enteric nervous system are various, including retrograde transport, hematogenous transmission and centrifugal transmission from the central nervous system. When viruses infect the enteric nervous system, they can cause clinical symptoms, such as abdominal pain, abdominal distension, early satiation, belching, diarrhea, and constipation, by recruiting macrophages, lymphocytes and neutrophils and regulating intestinal microbes. The findings of several case‒control studies suggest that viruses are the cause of some gastrointestinal motility disorders. It is concluded that one of the causes of gastrointestinal motility disorders is viral infection of the enteric nervous system. In such disorders, the relationships between viruses and nerves remain to be studied more deeply. Further studies are necessary to evaluate whether prophylactic antiviral therapy is feasible in gastrointestinal motility disorders.

Fused expression of Sm1-Chit42 proteins for synergistic mycoparasitic response of Trichoderma afroharzianum on Botrytis cinerea.

Sm1 and Chit42 of Trichoderma have been universally confirmed as crucial biocontrol factors against pathogen infection through induced resistance and mycoparasitism, respectively. However, not enough work has been conducted to understand the novel function of fused expression of these two proteins in Trichoderma. The results of this study demonstrated that Sm1-Chit42 protein (SCf) engineered T. afroharzianum strain OE:SCf exerted synergistic inhibition to Botrytis cinerea growth at multiple stages of mycoparasitic interaction of T. afroharzianum and B. cinerea including chemotropism sensing, hyphal coiling, hydrophobicity modulation, cell wall adhesion, virulence reduction and pathogen killing by ROS. These results highlight a novel mycoparasitic system in Trichoderma strains engineered with Sm1-Chit42 chimeric protein to combat B. cinerea growth and reproduction, which would lay a strong foundation for exploring a new engineered Trichoderma biofungicide created with chimeric proteins in the future.

Rh(III)-Catalyzed C-H Annulation of N-Nitrosoanilines with Iodonium Ylides for the Synthesis of N-Alkyl Indoles.

A novel protocol for synthesizing N-alkyl indoles from readily available N-nitrosoanilines and iodonium ylides through the rhodium(III)-catalyzed C-H bond activation/intramolecular cyclization reaction has been described. This strategy employs nitroso as a traceless directing group. The transformation features powerful reactivity, tolerates various functional groups, and proceeds with moderate yields under mild reaction conditions, providing a straightforward approach to access structurally diverse and valuable N-alkyl indole derivatives.

A lysosome-targetable fluorescent probe for the ratiometric detection of formaldehyde in living cells and in vivo.

Inspired by the synthetic method of benzoxazine derivatives and our previous research, a fluorescent probe (SWJT-6) was designed for formaldehyde (FA) detection based on the cyclization reaction. The synthetic SWJT-6 showed excellent colorimetric and ratiometric response to formaldehyde, and could be perfectly used as test strips to detect formaldehyde. It also showed a fast detection time (3 min), low detection limit (5.65 µM) and high selectivity for formaldehyde within various interfering analytes. In addition, SWJT-6 has been successfully applied in bioimaging of intracellular and lysosomal formaldehyde in both HeLa cells and zebrafish.

A mitochondria-targeted dual-response sensor for monitoring viscosity and peroxynitrite in living cells with distinct fluorescence signals.

Viscosity and peroxynitrite (ONOO-) are two significant indicators to affect and evaluate the mitochondrial functional status, which are nearly relational with pathophysiological process in many diseases. Developing suitable analytical methods for monitoring mitochondrial viscosity changes and ONOO- is thus of great importance. In this research, a new mitochondria-targeted sensor DCVP-NO2 for the dual determination of viscosity and ONOO- was exploited based on the coumarin skeleton. DCVP-NO2 displayed a red fluorescence "turn-on" response toward viscosity along with about 30-fold intensity increase. Meanwhile, it could be used as ratiometric probe for detection of ONOO- with excellent sensitivity and extraordinary selectivity for ONOO- over other chemical and biological species. Moreover, thanks to its good photostability, low cytotoxicity and ideal mitochondrion-targeting capability, DCVP-NO2 was successfully utilized for fluorescence imaging of viscosity variations and ONOO- in mitochondria of living cells through different channels. In addition, the results of cell imaging revealed that ONOO- would lead to the increase of viscosity. Taken together, this work provides a potential molecular tool for researching biological functions and interactions of viscosity and ONOO- in mitochondria.

Evaluation of different machine learning approaches and aerosol optical depth in PM2.5 prediction.

Atmospheric Aerosol Optical Depth (AOD), derived from polar-orbiting satellites, has shown potential in PM2.5 predictions. However, this important source of data suffers from low temporal resolution. Recently, geostationary satellites provide AOD data in high temporal and spatial resolution. However, the feasibility of these data in PM2.5 prediction needs further study. In this paper, we analyzed the impact of AOD derived from Himawari-8 in PM2.5 predictions. Moreover, by combining wavelet, machine learning techniques, and minimum redundancy maximum relevance (mRMR), a novel hybrid model was proposed. The results showed that AOD missing rate over Yangtze River Delta region is the highest in Nanjing, Hefei, and Maanshan. In addition, missing rates are the lowest in winter and summer (∼80%). Moreover, we found that considering AOD, as an auxiliary variable in the model, could not improve the accuracy of PM2.5 predictions, and in some cases decreased it slightly. In comparison with other models, our proposed hybrid model showed higher prediction accuracy, R2 is improved by 11.64% on average, and root mean square error, mean absolute error, and mean absolute percentage error is reduced by 26.82%, 27.24%, and 29.88% respectively. This research provides a general overview of the availability of Himawari-8 AOD data and its feasibility in PM2.5 predictions. In addition, it evaluates different machine learning approaches in PM2.5 predictions. Our proposed framework can be used in other regions to predict different air pollutants concentrations and can be used as an aid for air pollution controlling programs.

Quality and spatial intensity distribution characteristics of short-exposure spot images of a supercontinuum laser in a turbulent atmosphere.

In this study, considering the combined effects of atmospheric attenuation and turbulence, we examine the spot quality and spatial intensity distribution characteristics of a supercontinuum (SC) laser propagating in a turbulent atmosphere using the multi-layer phase-screen method. An increase in turbulence strength or a decrease in the initial beam radius resulted in a greater impact of the atmospheric turbulence on the SC laser. A decrease in source coherence results in the deterioration of the image quality of the far-field spot. Under moderate to strong turbulence, the scintillation index decreased as the source coherence decreased; however, the opposite trend was observed under weak turbulence. These results are significant for the advancement and optimization of SC laser systems.

Therapeutic drug monitoring of free vancomycin concentration in practice: A new analytical technique based on the HFCF-UF sample separation method.

The aim of this study was to establish a method for free vancomycin concentration determination in human plasma and apply it to clinical therapeutic drug monitoring (TDM). The unbound vancomycin in plasma was separated by the hollow fiber centrifugal ultrafiltration (HFCF-UF) technique and analyzed by HPLC. Chromatographic conditions were optimized, the specificity, linearity, precision, recovery and stability of the method were examined, and plasma samples of patients were measured. The standard curve for free vancomycin is y = 0.0277x - 0.0080 with good linearity within 0.25-50 µg·mL-1 . The relative and absolute recovery rates for vancomycin were 98.63-101.0% and 88.41-101.2%, respectively. The intraday and interday precision RSDs were <10%. Plasma was stable under several conditions. The TDM value of the free vancomycin concentration of 20 patients was 0.99-38.51 µg·mL-1 , and the correlation between the free and total concentrations was not significant. The unbound fraction of vancomycin ranged from 25.5 to 84.8%, with large variation. The operation of free vancomycin separation by HFCF-UF was simple and suitable for TDM in practice. The unbound fraction of vancomycin in clinical samples varied significantly between individuals. It is recommended to perform free concentration TDM in critically ill patients.

The spatial expression of mTORC2-AKT-IP3R signal pathway in mitochondrial combination of endoplasmic reticulum of maternal fetal interface trophoblast in intrahepatic cholestasis of pregnancy.

OBJECTIVES: Intrahepatic cholestasis of pregnancy (ICP) is complicated by adverse fetal outcomes and even fetal death, the mechanism remains unclear. This study aims at evaluating the differential expression of mTORC2-AKT-IP3R signaling pathway, which accurately regulate Ca2+ transfer across mitochondria-associated membranes (MAMs) and determine the stress intensity experienced by endoplasmic reticulum (ER) and mitochondria, in patients diagnosed with ICP. METHODS: We combined western blot analysis and placental immunofluorescence co-localization detection to assess the expression and co-localization of the mTORC2-AKT-IP3R signaling pathway in severe (maternal total bile acid (TBA) levels ≥40 µmol/L) and mild (maternal TBA 10-40 µmol/L) ICP. RESULTS: Compared with the control and mild ICP groups, phosphorylated protein kinase B (p-AKT) levels were significantly upregulated in the severe ICP group. Placental Rictor levels were lower in the mild ICP group than in the control group and were further downregulated in the severe ICP group. IP3R3 and p-IP3R3 levels were lower in placentas in the severe ICP group than in those in the mild ICP and control groups. Moreover, the co-localization of IP3R3 and p-AKT in patients in the mild and severe ICP groups was significantly elevated compared with that in patients in the control group. CONCLUSIONS: In patients with severe ICP, limited expression of Rictor and elevated p-AKT levels would suppress IP3R3/p-IP3R3 levels in MAMs. This inhibition might influence the transportation of Ca2+ from the ER to the mitochondria, thus weaken the stress adaptation associated with MAMs. Our results reveal the possible pathophysiological mechanism of adverse fetal outcomes in ICP.

ISRIB inhibits the senescence of type II pulmonary epithelial cells to alleviate pulmonary fibrosis induced by silica in mice.

The role and mechanisms of integrated stress response inhibitor (ISRIB) on silicosis are still not well defined. In the present study, the effects of ISRIB on cellular senescence and pulmonary fibrosis in silicosis were evaluated by RNA sequencing, micro-computed tomography, pulmonary function assessment, histological examination, and Western blot analysis. The results showed that ISRIB significantly reduced the degree of pulmonary fibrosis in mice with silicosis and reduced the expression of type I collagen, fibronectin, α-smooth muscle actin, and transforming growth factor-ß1. Both in vivo and in vitro results showed that ISRIB reversed the expression of senescence-related factors ß-galactosidase, phosphor-ataxia telangiectasia mutated, phosphor-ataxia telangiectasia and Rad3-related protein, p-p53, p21, p16, and plasminogen activator inhibitor type 1. The aforementioned results were consistent with the sequencing results. These findings implied that ISRIB might reduce the degree of pulmonary fibrosis in mice with silicosis by inhibiting the cellular senescence of alveolar epithelial cell type II.

Quantitative Super-Resolution Microscopy Reveals the Relationship between CENP-A Stoichiometry and Centromere Physical Size.

Centromeric chromatin is thought to play a critical role in ensuring the faithful segregation of chromosomes during mitosis. However, our understanding of this role is presently limited by our poor understanding of the structure and composition of this unique chromatin. The nucleosomal variant, CENP-A, localizes to narrow regions within the centromere, where it plays a major role in centromeric function, effectively serving as a platform on which the kinetochore is assembled. Previous work found that, within a given cell, the number of microtubules within kinetochores is essentially unchanged between CENP-A-localized regions of different physical sizes. However, it is unknown if the amount of CENP-A is also unchanged between these regions of different sizes, which would reflect a strict structural correspondence between these two key characteristics of the centromere/kinetochore assembly. Here, we used super-resolution optical microscopy to image and quantify the amount of CENP-A and DNA within human centromere chromatin. We found that the amount of CENP-A within CENP-A domains of different physical sizes is indeed the same. Further, our measurements suggest that the ratio of CENP-A- to H3-containing nucleosomes within these domains is between 8:1 and 11:1. Thus, our results not only identify an unexpectedly strict relationship between CENP-A and microtubules stoichiometries but also that the CENP-A centromeric domain is almost exclusively composed of CENP-A nucleosomes.

The heterozygous mutations of SLC26A8 are not the main actors for male infertility.

Male infertility has become a serious health and social problem troubling approximately 15% of couples worldwide; however, the genetic and phenotypic heterogeneity of human infertility poses a substantial obstacle to effective diagnosis and therapy. A previous study reported that heterozygous mutations in solute carrier family 26 member 8 (SLC26A8, NG_033897.1) were causatively linked to asthenozoospermia. Interestingly, in our research, three deleterious heterozygous mutations of SLC26A8 were separately detected in three unrelated patients who were suffered from teratozoospermia. These three heterozygous mutations resulted in the reduction of SLC26A8 expression in transfected cells, while no disrupted expression of SLC26A8 was observed in sperm from the affected individuals. Noticeably, two of the three SLC26A8 heterozygous mutations detected in the patients were inherited from their fertile fathers. Thus, we suggested that male infertility associated with SLC26A8 mutations should be involved in a recessive-inherited pattern, considering the infertile homozygous Slc26a8 KO male mice, the contribution of heterozygous mutations in SLC26A8 in male infertility needs further deep research.

Impaired Function of a Rare Mutation in the MMUT Gene Causes Methylmalonic Acidemia in a Chinese Patient.

Methylmalonic acidemia (MMA) is an autosomal recessive metabolic disorder mainly caused by mutations in the methylmalonyl coenzyme A mutase (MCM) gene (MMUT) and leads to the reduced activity of MCM. In this study, a 3-year-old girl was diagnosed with carnitine deficiency secondary to methylmalonic acidemia by tandem mass spectrometry (MS/MS) and gas chromatography/mass spectrometry (GS/MS). Whole-exome sequencing (WES) was performed on the patient and identified two compound heterozygous mutations in MMUT: c.554C>T (p. S185F) and c.729-730insTT (p. D244Lfs ∗ 39). Bioinformatics analysis predicted that the rare missense mutation of c.554C>T would be damaging. Moreover, this rare mutation resulted in the reduced levels of MMUT mRNA and MMUT protein. Collectively, our findings provide a greater understanding of the effects of MMUT variants and will facilitate the diagnosis and treatment of patients with MMA.

Isolation, Identification, and Characterization of an Efficient Siderophore Producing Bacterium From Heavy Metal Contaminated Soil.

An efficient siderophore producing strain, YQ9, was isolated from heavy metal contaminated soil and identified as Burkholderia vietnamiensis. To the best of our known, the strain owns the highest siderophore producing capacity among genus Burkholderia with 96.6% siderophore unit. Moreover, B. vietnamiensis YQ9 has good adaptability to different pH values, temperatures, NaCl, and Fe3+ concentrations. In addition, the minimum inhibitory concentration (MIC) of heavy metals and antibiotics were also tested. It was found that the MIC values of strain YQ9 to several major soil heavy metal pollutants, such as Pb2+, Zn2+, Cu2+, and Cd2+ reached 3000, 5000, 4500, and 1000 µmol·L-1, respectively. And YQ9 was sensitive to 4 of 8 test antibiotics, including rifampicin, kanamycin, doxycycline hyclate, and gentamicin (25, 25, 30, and 30 µg·mL-1, respectively). Strain YQ9 also owns the ability to produce indole-3-acetic acid (IAA) and 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase and dissolve phosphorus. The IAA production capacity was 6.93 mg·L-1, the ACC deaminase activity was 8.71 µmol α-KA·(h·mg)-1, and the phosphorus dissolving capacity of YQ9 was 104.05 mg·L-1. The traits were excellent, and the strain was qualified as a candidate for microbial reinforcement of phytoremediation in soil contaminated by heavy metals.