A CD3G homozygous pathogenic variant in a Chinese child with lupus-like disease, autoimmune thyroiditis and immunodeficiency.

BACKGROUND: The T-cell receptor (TCR)/CD3 complex plays a crucial role in T-cell development and immune regulation. CD3G gene encodes one of the CD3 subunits named CD3γ, and its deficiency can cause autoimmune disorders, immunodeficiency and recurrent infections. To date, only 13 patients with CD3G variants have been reported. CASE REPORT: We report a 10-year-old Chinese boy presented with lupus-like disease in addition to autoimmune thyroiditis, asthma, immunodeficiency and recurrent infection. Flow cytometric analysis revealed apparently decreased levels of CD3+ and CD8+ T cells but mildly decreased CD4+ T cells. However, the activation of T cells and B cells increased. RESULTS: Trio-based whole-exome sequencing revealed a homozygous pathogenic variant (c.213delA, p.Lys71fs) of CD3G gene in the proband. His parents were both heterozygous carriers of this variant. CONCLUSION: This is the first patient who met the diagnostic criteria for systemic lupus erythematosus by the Systemic Lupus International Collaborating Clinics (SLICC) group. In addition to low T cells and low Treg cells, our study further revealed T cells and B cells activation enhanced in CD3γ deficiency patient, which may play an important role in autoimmunity. We believe that our study makes a significant contribution to the literature and will provide further insight into CD3γ deficiency and monogenic lupus.

Acute cold stress leads to zebrafish ovarian dysfunction by regulating miRNA and mRNA.

Temperature is a critical factor that regulates the reproduction processes in teleost. However, the gonadal response mechanism to cold stress in fish remains largely unknown. In the present study, female zebrafish were exposed to different extents of low temperatures at 18 °C and 10 °C for 48 h. The ovarian histology was remarkably damaged after cold stress exposure. Integrated analysis of miRNA-mRNA was used to investigate the ovarian response to acute cold stress. A large number of mRNAs and miRNAs were altered by cold stress, which are involved in extensive biological processes. It is indicated that the signal transduction of MAPK and Calcium signaling pathway is highly engaged in zebrafish ovary to adapt to cold stress. The immune system was dysregulated by cold stress while the ovarian autophagy was activated. Remarkably increased gene number related to reproductive functions was identified in the cold stress at 10 °C compared to the control. The cold stress-induced dysregulated reproductive genes include star, hsd3b1, hsd17b1, inha, insl3, amh, nanos1 and foxl2. Combined with the dysregulated insulin, IGF and progesterone signaling, it is suggested that cold stress affects ovarian function in multiple aspects, including oocyte meiosis, folliculogenesis, final maturation and ovarian maintenance. On the other hand, the ovarian miRNA-mRNA regulatory network response to cold stress was also constructed. Overall, our result revealed the ovarian response to cold stress in zebrafish and provided insight into the fish adaptation mechanism to acute temperature change.

Degradable Self-Destructive Redox-Responsive System Based on Mesoporous Organosilica Nano-Vehicles for Smart Delivery of Fungicide.

The development of stimuli-responsive controlled release formulations is a potential method of improving pesticide utilization efficiency and alleviating current pesticide-related environmental pollution. In this study, a self-destruction redox-responsive pesticide delivery system using biodegradable disulfide-bond-bridged mesoporous organosilica (DMON) nanoparticles as the porous carriers and coordination complexes of gallic acid (GA) and Fe(III) ions as the capping agents were established for controlling prochloraz (PRO) release. The GA-Fe(III) complexes deposited onto the surface of DMON nanoparticles could effectively improve the light stability of prochloraz. Due to the decomposition of GA-Fe(III) complexes, the nano-vehicles had excellent redox-responsive performance under the reducing environments generated by the fungus. The spreadability of PRO@DMON-GA-Fe(III) nanoparticles on the rice leaves was increased due to the hydrogen bonds between GA and rice leaves. Compared with prochloraz emulsifiable concentrate, PRO@DMON-GA-Fe(III) nanoparticles showed better fungicidal activity against Magnaporthe oryzae with a longer duration under the same concentration of prochloraz. More importantly, DMON-GA-Fe(III) nanocarriers did not observe obvious toxicity to the growth of rice seedlings. Considering non-toxic organic solvents and excellent antifungal activity, redox-responsive pesticide controlled release systems with self-destruction properties have great application prospects in the field of plant disease management.

Zeolitic Imidazole Framework-90-Based Pesticide Smart-Delivery System with Enhanced Antimicrobial Performance.

Multimodal antimicrobial technology is regarded as a promising strategy for controlling plant diseases because it enhances antimicrobial efficacy by blocking multiple pesticide-resistance pathways. In this work, a pH-responsive multimodal antimicrobial system was constructed based on ZIF-90 for the controlled release of kasugamycin (KSM). A series of physicochemical characterizations confirmed the successful fabrication of ZIF-90-KSM. The results indicated that the loading capacity of ZIF-90-KSM for KSM was approximately 6.7% and that the ZIF-90 nanocarriers could protect KSM against photodegradation effectively. The acid pH at the site of disease not only decompose the Schiff base bonds between KSM and ZIF-90, but also completely dissolved the nanocarriers. The simultaneous release of KSM and Zn2+ ions was able to achieve multimodal antimicrobial functions during disease occurs. A bioactivity survey indicated that ZIF-90-KSM had superior fungicidal activity and longer duration against Magnaporthe oryzae than KSM aqueous solution. In addition, the phytotoxicity assessment of ZIF-90-KSM on rice plants did not reveal any adverse effects. Therefore, ZIF-90-KSM prepared by Schiff base reaction has great potential for achieving synergistic antifungal functions and provides an eco-friendly approach to manage rice diseases.

Pectin functionalized metal-organic frameworks as dual-stimuli-responsive carriers to improve the pesticide targeting and reduce environmental risks.

Encapsulation of active ingredients into intelligent response controlled release carriers has been recognized as a promising approach to enhance the utilization efficiency and reduce the environmental risks of pesticides. In this work, an intelligent redox and pectinase dual stimuli-responsive pesticide delivery system was constructed by bonding pectin with metal-organic frameworks (FeMOF nanoparticles) which were loaded with pyraclostrobin (PYR@FeMOF-pectin nanoparticles). The successful fabrication of PYR@FeMOF-pectin nanoparticles was proved by a series of physicochemical characterizations. The results indicated that the loading capacity of PYR@FeMOF-pectin nanoparticles for pyraclostrobin was approximately 20.6%. The pectin covered on the surface of PYR@FeMOF nanoparticles could protect pyraclostrobin from photolysis and improve their spreadability on rice blades effectively. Different biological stimuli associated with Magnaporthe oryzae could trigger the release of pyraclostrobin from the pesticide-loaded core-shell nanoparticles, resulting in the death of pathogens. The bioactivity survey determined that PYR@FeMOF-pectin nanoparticles had a superior fungicidal activity and a longer duration against Magnaporthe oryzae than pyraclostrobin suspension concentrate. In addition, the FeMOF-pectin nanocarriers showed no obvious phytotoxicity and could enhance the shoot length and root length of rice plants. More importantly, PYR@FeMOF-pectin nanoparticles had an 8-fold reduction in acute toxicity to zebrafish than that of pyraclostrobin suspension concentrate. Therefore, the dual-responsive FeMOF-pectin nanocarriers have great potential for realizing site-specific pesticide delivery and promoting plant growth.

Paenibacillus tianjinensis sp. nov., isolated from corridor air.

A Gram-stain-positive, facultatively anaerobic, non-motile, endospore-forming and rod-shaped bacterium, occurring singly or in pairs, designated TB2019T, was isolated from environmental monitoring samples of corridor air collected at the Tianjin Institute for Drug Control, Tianjin Province (PR China). The isolate was able to grow at 15-40 °C (optimum growth at 37 °C), pH 6.0-8.0 (pH 7.0) and in the presence of 0-2% (w/v) NaCl (0% NaCl). Comparison of 16S rRNA gene sequences indicated that TB2019T was most closely related to Paenibacillus typhae CGMCC 1.11012T (98.63%), Paenibacillus albidus Q4-3T (98.19%), Paenibacillus borealis DSM 13188T (97.55%), Paenibacillus helianthi P26ET (97.33%) and Paenibacillus odorifer DSM 15391T (97.19%). The digital DNA-DNA hybridization and the average nucleotide identity values between TB2019T and the five type strains mentioned above ranged from 20.7 to 25.0% and 75.2 to 81.3%, respectively, and the genomic DNA G+C content was 49.52 mol%. The diagnostic cell-wall sugar was ribose, and the diagnostic amino acid was meso-diaminopimelic acid. The polar lipids of TB2019T included diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, three unidentified aminophospholipids and one unidentified phospholipid. MK-7 was the predominant menaquinone, and anteiso-C15:0 (30.6%) was the major fatty acid. Based on the polyphasic taxonomic data, strain TB2019T represents a novel species of the genus Paenibacillus, for which the name Paenibacillus tianjinensis sp. nov. is proposed. The type strain is TB2019T (=CICC 25065T=JCM 34610T).