Prenatal diagnosis and family analysis of 17q12 microdeletion syndrome with fetal renal abnormalities.

Purpose: To analyze the prenatal diagnosis, parental verification, and pregnancy outcomes of three fetuses with 17ql2 microdeletion syndrome. Methods: We retrospectively reviewed 46 singleton pregnancies with anomalies in the urinary system who underwent amniocentesis from Feb 2022 to October 2023 in the Prenatal Diagnosis Center of Lianyungang Maternal and Child Health Hospital. These fetuses were subjected to chromosomal microarray analysis (CMA) and/or trio whole-exome sequencing (Trio-WES). We specifically evaluated these cases' prenatal renal ultrasound findings and clinical characteristics of the affected parents. Results: Three fetuses were diagnosed as 17q12 microdeletions, and the detection rate was 6.5% in fetuses with anomalies in the urinary system (3/46). The heterogeneous deletions range from 1.494 to 1.66 Mb encompassing the complete hepatocyte nuclear factor 1 homeobox B (HNF1B) gene. Fetuses with 17q12 deletion exhibited varied renal phenotypes. Moreover, the clinical phenotypes of the affected parents differed greatly in the two cases (case 2 and case 3) in which the deletion was inherited. For case 3, the mother manifested classic symptoms of 17q12 deletion syndrome as well as unreported characteristics, such as very high myopia. Conclusion: Our findings demonstrate the necessity and significance of offering prenatal genetic testing when various renal anomalies are detected. In addition, our study broadens the phenotypic spectrum of 17q12 deletions. Most importantly, our findings may allow timely supportive genetic counseling and guidance for pregnancy in affected families, e.g., with the help of preimplantation genetic testing (PGT).

Potential Mechanism and Involvement of P120-Catenin in the Malignant Biology of Glioma.

Objective: This study analyzed the influence of p120-catenin (CTNND1) on the malignant characteristics of glioma and elucidated the potential underlying mechanism. Methods: The p120 expression level was assessed in the brain tissues of 42 glioma patients and 10 patients with epilepsy by using the immunohistochemical method. Meanwhile, quantitative PCR technology was employed to assess the expression of P120 in the brain tissues of 71 glioma patients and 13 epilepsy patients. LN229, U251, and U87 glioma cells were used for in vitro analysis and categorized into four treatment groups: siRNA-BC group (no RNA sequence was transfected), siRNA-NC group (transfected control RNA sequences with no effect), and siRNA-1 and siRNA-2 groups (two p120-specific interfering RNA transfection). p120 expression in these treatment groups was quantified by western blotting assay. The migratory and invasive capabilities of glioma cells were studied by wound healing assay and Transwell invasion assay, respectively, under different treatment conditions. MTT assay and cell cycle and apoptosis assay were used to determine glioma cell proliferation and apoptosis, respectively. Enzyme-labeled assay was performed to measure intracellular calcium ion concentration. Immunofluorescence assay was performed for determining microtubule formation and glioma cell distribution. Results: Brain tissues of the glioma group exhibited a remarkable increase in the p120 expression level as compared to brain tissues of the nontumor group (P < 0.05). Furthermore, a strong positive correlation was noted between the malignancy degree in glioma brain tissues and p120 expression in Western blotting (r = 0.906, P = 0.00) and QT-PCR (F=830.6, P＜0.01). Compared to the BC and NC groups, the siRNA transfection groups showed a significant suppression in p120 expression in glioma cells (P < 0.05), with a marked attenuation in the invasive, migratory, and proliferative capabilities of glioma cells as well as an increase in apoptotic potential (P < 0.05). Enzyme-labeled assay showed a remarkable increase in calcium concentration in glioma cells after siRNA treatment. Immunofluorescence assay revealed that the microtubule formation ability of glioma cells reduced after siRNA treatment. Conclusion: p120 has a pivotal involvement in facilitating glioma cell invasion and proliferation by potentially modulating these processes through its involvement in microtubule formation and regulation of intracellular calcium ion levels.

Two novel compound heterozygous loss-of-function mutations cause fetal IRAK-4 deficiency presenting with Pseudomonas Aeruginosa sepsis.

PURPOSE: To report a case of a five-month-old Chinese infant who died of interleukin-1 receptor-associated kinase-4 (IRAK-4) deficiency presenting with rapid and progressive Pseudomonas aeruginosa sepsis. METHODS: The genetic etiology of IRAK-4 deficiency was confirmed through trio-whole exome sequencing and Sanger sequencing. Functional consequences were invested using an in vitro minigene splicing assay. RESULTS: Trio-whole exome sequencing of genomic DNA identified two novel compound heterozygous mutations, IRAK-4 (NM_016123.3): c.942-1G > A and c.644_651+ 6delTTGCAGCAGTAAGT in the proband, which originated from his symptom-free parents. These mutations were predicted to cause frameshifts and generate three truncated proteins without enzyme activity. CONCLUSIONS: Our findings expand the range of IRAK-4 mutations and provide functional support for the pathogenic effects of splice-site mutations. Additionally, this case highlights the importance of considering the underlying genetic defects of immunity when dealing with unusually overwhelming infections in previously healthy children and emphasizes the necessity for timely treatment with wide-spectrum antimicrobials.

Self-Assembled Viscoelastic Surfactant Micelles with pH-Responsive Behavior: A New Fracturing-Displacement Integrated Working Fluid for Unconventional Reservoirs.

The integrated fracturing and oil recovery strategy is a new paradigm for achieving sustainable and cost-effective development of unconventional reservoirs. However, a single type of working fluid cannot simultaneously meet the different needs of fracturing and oil displacement processes. Here, we develop a pH-responsive fracturing-displacement integrated working fluid based on the self-assembled micelles of N,N-dimethyl oleoamine propylamine (DOAPA) and succinic acid (SA). By adjusting the pH of the working fluid, the DOAPA and SA molecules can be switched repeatedly between highly viscoelastic wormlike micelles and aqueous low-viscosity spherical micelles. The zero-shear viscosity of the working fluid enriched the wormlike micelles can reach more than 93,100 mPa·s, showing excellent viscoelasticity and sand-carrying properties. The working fluid is easy to gel-break when it encounters oil, generating a low-viscosity liquid without residue. In addition, the system has strong interfacial activity, which can greatly reduce the oil-water interfacial tension to form emulsions and can achieve reversible demulsification and re-emulsification by adjusting pH. Through the designed and fabricated microfluidic chip, it can be visualized that under the synergistic effect of viscoelasticity and interfacial activity DOAPA/SA can effectively expand the swept volume of tight fractured formations, promote pore wetting reversal and crude oil emulsification, and improve the displacement efficiency. The DOAPA/SA meets the design requirements of the fracturing-displacement integrated working fluids and provides a novel method and idea for constructing the integrated working fluids suitable for fracturing and displacement in unconventional reservoirs.

Transgenic mice applications in the study of endometriosis pathogenesis.

Endometriosis (EM), characterized by ectopic growth of endometrial tissues and recurrent pelvic pain, is a common disease with severe negative impacts on the life quality of patients. Conventional uterine tissue transplantation-based models have been broadly used to investigate the pathogenic mechanism(s) of EM. Transgenic mice with whole body or uterine/pelvic tissue-specific labelling by the expression of GFP, ß-gal or other light-emitting or chromogenic markers enable investigators to analyze the contribution to endometriotic lesions by the donor or recipient side after uterine tissue transplantation. Moreover, when coupled to uterine tissue transplantation, transgenic mice with a specific EM-related gene knocked out or overexpressed make it possible to determine the gene's in vivo role(s) for EM pathogenesis. Furthermore, observations on the rise of de novo endometriotic lesions as well as structural/functional changes in the eutopic endometrium or pelvic tissues after gene manipulation will directly relate the cognate gene to the onset of EM. A major advantage of transgenic EM models is their efficiency for analyzing gene interactions with hormonal, dietetic and/or environmental factors. This review summarizes the features/sources/backgrounds of transgenic mice and their applications to EM studies concerning hormonal regulation, angiogenesis and inflammation. Findings from these studies, the advantages/disadvantages of transgenic EM models, and future expectations are also discussed.

Replacement of Corn with Different Levels of Wheat Impacted the Growth Performance, Intestinal Development, and Cecal Microbiota of Broilers.

Replacing corn with different levels of wheat in the iso-energy and -protein diet of broilers and the impacts on growth performance and intestinal homeostasis of broilers under the condition of supplying the multienzyme complex were evaluated in this study. A total of 480 10-day-old male broilers were assigned randomly to the low-level wheat group (15% wheat and 35.18% corn), the medium-level wheat group (30% and 22.27%), and the high-level wheat group (55.77% wheat without corn) until 21 d. The different levels of wheat supplementation did not affect hepatic function, serum glycolipid profile, or bone turnover. The replacement of corn with 55% wheat in the diet of broilers increased the body weight at 21 d and feed intake during 10 to 21 d (both p < 0.05), with a comparable feed conversion ratio. Compared with the low-wheat group, the dietary addition of medium or high wheat levels notably increased the ratio of villus height to crypt depth in the duodenum (p < 0.05) and the ileal villus height (p < 0.05). Meanwhile, the supplementation of medium and high wheat in the diet increased the proportion of Bacteroidetes, and a diet with high wheat proportion elevated the content of Firmicutes when compared to the low-level wheat group (both p < 0.05). In addition, the diet containing 30-55% wheat enhanced the anti-inflammatory capability in both the ileum and the serum. These findings suggest that the replacement of corn with 55% wheat in the diet improved the growth performance of 21-day-old broilers, which might be linked to the alteration in intestinal morphology and cecal microbiota.

Insights into the biodegradation of pentachlorobiphenyl by Microbacterium paraoxydans: proteomic and metabolomic studies.

Bacterial degradation mechanism for high chlorinated pentachlorobiphenyl (PentaCB) with worse biodegradability has not been fully elucidated, which could limit the full remediation of environments afflicted by the complex pollution of polychlorinated biphenyls (PCBs). In this research, a new PentaCB-degrading bacterium Microbacterium paraoxydans that has not been reported was obtained using enzymatic screening method. The characteristics of its intracellular enzymes, proteome and metabolome variation during PentaCB degradation were investigated systematically compared to non-PentaCB conditions. The findings indicate that the degradation rate of PentaCB (1 mg/L) could reach 23.9% within 4 hours and achieve complete degradation within 12 hours, with the mixture of intracellular enzymes being most effective at a pH of 6.0. During the biodegradation of PentaCB, the 12 up-regulated proteins characterized included ABC transporter PentaCB-binding protein, translocase protein TatA, and signal peptidase I (SPase I), indicating the presence of functional proteins for PentaCB degradation in both the cytoplasm and the outer surface of the cytoplasmic membrane. Furthermore, five differentially enriched metabolites were strongly associated with the aforementioned proteins, especially the up-regulated 1, 2, 4-benzenetriol which feeds into multiple degradation pathways of benzoate, chlorocyclohexane, chlorobenzene and aminobenzoate. These relevant results help to understand and speculate the complex mechanisms regarding PentaCB degradation by M. paraoxydans, which have both theoretical and practical implications for PCB bioremediation.

Sub-Nanogram Resolution Measurement of Inertial Mass and Density Using Magnetic-Field-Guided Bubble Microthruster.

Artificial micro/nanomotors using active particles hold vast potential in applications such as drug delivery and microfabrication. However, upgrading them to micro/nanorobots capable of performing precise tasks with sophisticated functions remains challenging. Bubble microthruster (BMT) is introduced, a variation of the bubble-driven microrobot, which focuses the energy from a collapsing microbubble to create an inertial impact on nearby target microparticles. Utilizing ultra-high-speed imaging, the microparticle mass and density is determined with sub-nanogram resolution based on the relaxation time characterizing the microparticle's transient response. Master curves of the BMT method are shown to be dependent on the viscosity of the solution. The BMT, controlled by a gamepad with magnetic-field guidance, precisely manipulates target microparticles, including bioparticles. Validation involves measuring the polystyrene microparticle mass and hollow glass microsphere density, and assessing the mouse embryo mass densities. The BMT technique presents a promising chip-free, real-time, highly maneuverable strategy that integrates bubble microrobot-based manipulation with precise bioparticle mass and density detection, which can facilitate microscale bioparticle characterizations such as embryo growth monitoring.

Lead exposure induces neurodysfunction through caspase-1-mediated neuronal pyroptosis.

Chronic lead (Pb) exposure causes neurodysfunction and contributes to the development of neurodegenerative disease. However, the mechanism of Pb-induced neurological dysfunction have yet to be fully elucidated. This study determined the role pyroptosis plays in Pb-induced neurodysfunction in neurons. We used both in vitro and in vivo approaches to explore whether Pb exposure induces caspase-1-mediated pyroptosis in neurons and its relationship to Pb-induced neurological disorders. Our findings showed that caspase-1-mediated pyroptosis in Pb-exposed neurons activated glycogen synthase kinase 3 protease activity by disrupting Ca2+/calmodulin-dependent protein kinase II/cAMP-response element binding protein pathway, leading to neurological disorders. Moreover, the caspase-1 inhibition VX-765 or the non-steroidal anti-inflammatory drug sodium para-aminosalicylic acid (PAS-Na) attenuated the Pb-induced neurological disorders by alleviating caspase-1 mediated neuronal pyroptosis. Our novel studies suggest that caspase-1-mediated pyroptosis in neurons represents a potential mechanism for Pb-induced neurodysfunction, identifying a putative target for attenuating the neurodegenerative effects induced by this metal.

Sodium para-aminosalicylic acid attenuates combined manganese/iron-induced cortical synaptic damage in rats.

We established experimental models of manganese (Mn) and iron (Fe) exposure in vitro and in vivo, and addressed the effects of manganese and iron combined exposure on the synaptic function of pheochromocytoma derived cell line 12 (PC12) cells and rat cortex, respectively. We investigated the protective effect of sodium para-aminosalicylate (PAS-Na) on manganese and iron combined neurotoxicity, providing a scientific basis for the prevention and treatment of ferromanganese combined neurotoxicity. Western blot and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were performed to detect the expression levels of protein and mRNA related to synaptic damage. Y-maze novelty test and balance beam test were used to evaluate the motor and cognitive function of rats. Haematoxylin and eosin (H&E) and Nissl staining were performed to observe the cortical damage of rats. The results showed that the combined exposure of Mn and Fe in rats led to a synergistic effect, attenuating growth and development, and altering learning and memory as well as motor function. The combination of Mn and Fe also caused damage to the synaptic structure of PC12 cells, which is manifested as swelling of dendrites and axon terminals, and even lead to cell death. PAS-Na displayed some antagonistic effects against the Mn- and Fe-induced synaptic structural damage, growth, learning and memory impairment.

Tuning the Electronic Structures of Anchor Sites to Achieve Zero-Valence Single-Atom Catalysts for Advanced Hydrogenation.

Single-atom catalysts (SACs) have recently become highly attractive for selective hydrogenation reactions owing to their remarkably high selectivity. However, compared to their nanoparticle counterparts, atomically dispersed metal atoms in SACs often show inferior activity and are prone to aggregate under reaction conditions. Here, by theoretical calculations, we show that tuning the local electronic structures of metal anchor sites on g-C3N4 by doping B atoms (BCN) with relatively lower electronegativity allows achieving zero-valence Pd SACs with reinforced metal-support orbital hybridizations for high stability and upshifted Pd 4d orbitals for high activity in H2 activation. The precise synthesis of Pd SACs on BCN supports with varied B contents substantiated the theoretical prediction. A zero-valence Pd1/BCN SAC was achieved on a BCN support with a relatively low B content. It exhibited much higher stability in a H2 reducing environment, and more strikingly, a hydrogenation activity, approximately 10 and 34 times greater than those high-valence Pd1/g-C3N4 and Pd1/BCN with a high B content, respectively.

Fabrication of Nitrogen Based Magnetic Conjugated Microporous Polymer for Efficient Extraction of Neonicotinoids in Water Samples.

Facile and sensitive methods for detecting neonicotinoids (NEOs) in aquatic environments are crucial because they are found in extremely low concentrations in complex matrices. Herein, nitrogen-based magnetic conjugated microporous polymers (Fe3O4@N-CMP) with quaternary ammonium groups were synthesized for efficient magnetic solid-phase extraction (MSPE) of NEOs from tap water, rainwater, and lake water. Fe3O4@N-CMP possessed a suitable specific surface area, extended π-conjugated system, and numerous cationic groups. These properties endow Fe3O4@N-CMP with superior extraction efficiency toward NEOs. The excellent adsorption capacity of Fe3O4@N-CMP toward NEOs was attributed to its π-π stacking, Lewis acid-base, and electrostatic interactions. The proposed MSPE-HPLC-DAD approach based on Fe3O4@N-CMP exhibited a wide linear range (0.1-200 µg/L), low detection limits (0.3-0.5 µg/L), satisfactory precision, and acceptable reproducibility under optimal conditions. In addition, the established method was effectively utilized for the analysis of NEOs in tap water, rainwater, and lake water. Excellent recoveries of NEOs at three spiked levels were in the range of 70.4 to 122.7%, with RSDs less than 10%. This study provides a reliable pretreatment method for monitoring NEOs in environmental water samples.

A pH/ROS dual-responsive system for effective chemoimmunotherapy against melanoma via remodeling tumor immune microenvironment.

Chemotherapeutics can induce immunogenic cell death (ICD) in tumor cells, offering new possibilities for cancer therapy. However, the efficiency of the immune response generated is insufficient due to the inhibitory nature of the tumor microenvironment (TME). Here, we developed a pH/reactive oxygen species (ROS) dual-response system to enhance chemoimmunotherapy for melanoma. The system productively accumulated in tumors by specific binding of phenylboronic acid (PBA) to sialic acids (SA). The nanoparticles (NPs) rapidly swelled and released quercetin (QUE) and doxorubicin (DOX) upon the stimulation of tumor microenvironment (TME). The in vitro and in vivo results consistently demonstrated that the NPs improved anti-tumor efficacy and prolonged survival of mice, significantly enhancing the effects of the combination. Our study revealed DOX was an ICD inducer, stimulating immune responses and promoting maturation of dendritic cells (DCs). Additionally, QUE served as a TME regulator by inhibiting the cyclooxygenase-2 (COX2)-prostaglandin E2 (PGE2) axis, which influenced various immune cells, including increasing cytotoxic T cells (CLTs) infiltration, promoting M1 macrophage polarization, and reducing regulatory T cells (Tregs) infiltration. The combination synergistically facilitated chemoimmunotherapy efficacy by remodeling the immunosuppressive microenvironment. This work presents a promising strategy to increase anti-tumor efficiency of chemotherapeutic agents.

1-Methyltryptophan treatment ameliorates high-fat diet-induced depression in mice through reversing changes in perineuronal nets.

Depression and obesity are prevalent disorders with significant public health implications. In this study, we used a high-fat diet (HFD)-induced obese mouse model to investigate the mechanism underlying HFD-induced depression-like behaviors. HFD-induced obese mice exhibited depression-like behaviors and a reduction in hippocampus volume, which were reversed by treatment with an indoleamine 2,3-dioxygenase (IDO) inhibitor 1-methyltryptophan (1-MT). Interestingly, no changes in IDO levels were observed post-1-MT treatment, suggesting that other mechanisms may be involved in the anti-depressive effect of 1-MT. We further conducted RNA sequencing analysis to clarify the potential underlying mechanism of the anti-depressive effect of 1-MT in HFD-induced depressive mice and found a significant enrichment of shared differential genes in the extracellular matrix (ECM) organization pathway between the 1-MT-treated and untreated HFD-induced depressive mice. Therefore, we hypothesized that changes in ECM play a crucial role in the anti-depressive effect of 1-MT. To this end, we investigated perineuronal nets (PNNs), which are ECM assemblies that preferentially ensheath parvalbumin (PV)-positive interneurons and are involved in many abnormalities. We found that HFD is associated with excessive accumulation of PV-positive neurons and upregulation of PNNs, affecting synaptic transmission in PV-positive neurons and leading to glutamate-gamma-aminobutyric acid imbalances in the hippocampus. The 1-MT effectively reversed these changes, highlighting a PNN-related mechanism by which 1-MT exerts its anti-depressive effect.

Serum neuroactive metabolites of the tryptophan pathway in patients with acute phase of affective disorders.

Background: Many studies showed disrupted tryptophan metabolism in patients with affective disorders. The aims of this study were to explore the differences in the metabolites of tryptophan pathway (TP) and the relationships between TP metabolites and clinical symptoms, therapeutic effect in patients with bipolar disorder with acute manic episode (BD-M), depressive episode (BD-D) and major depressive disorder (MDD). Methods: Patients with BD-M (n=52) and BD-D (n=39), MDD (n=48) and healthy controls (HCs, n=49) were enrolled. The serum neuroactive metabolites levels of the TP were measured by liquid chromatography-tandem mass spectrometry. Hamilton Depression Scale-17 item (HAMD-17) and Young Mania Rating Scale (YMRS) were used to evaluate depressive and manic symptoms at baseline and after 8 weeks of antidepressants, mood stabilizers, some also received antipsychotic medication. Results: The levels of tryptophan (TRP) and kynurenic acid (KYNA) were significantly lower and the ratios of tryptophan/kynurenine (TRP/KYN), 5-hydroxytryptamine/tryptophan (5-HT/TRP), quinolinic acid/kynurenic acid (QUIN/KYNA) were higher in BD-M, BD-D, MDD vs. HC. The levels of QUIN and the ratios of QUIN/KYNA were higher in BD-M than in BD-D, MDD, and HCs. The 5-hydroxyindoleacetic acid (5-HIAA) levels of patients with MDD were significantly higher than those in BD-M and BD-D. Binary logistic regression analysis showed the lower peripheral KYNA, the higher the QUIN level, and the higher the risk of BD-M; the lower peripheral KYNA and the higher KYN/TRP and 5-HT/TRP, the higher the risk of BD-D; and the lower the peripheral KYNA level and the higher the KYN/TRP and 5-HT/TRP, the higher the risk of MDD. Correlation analysis, showing a significant association between tryptophan metabolites and improvement of clinical symptoms, especially depression symptoms. Conclusions: Patients with affective disorders had abnormal tryptophan metabolism, which involved in 5-HT and kynurenine pathway (KP) sub-pathway. Tryptophan metabolites might be potential biomarkers for affective disorders and some metabolites have been associated with remission of depressive symptoms.

SIRT1/P53 in retinal pigment epithelial cells in diabetic retinopathy: a gene co-expression analysis and He-Ying-Qing-Re formula treatment.

Objective: Diabetic retinopathy (DR) is a severe diabetic complication that leads to severe visual impairment or blindness. He-Ying-Qing-Re formula (HF), a traditional Chinese medicinal concoction, has been identified as an efficient therapy for DR with retinal vascular dysfunction for decades and has been experimentally reported to ameliorate retinal conditions in diabetic mice. This study endeavors to explore the therapeutic potential of HF with key ingredients in DR and its underlying novel mechanisms. Methods: Co-expression gene modules and hub genes were calculated by weighted gene co-expression network analysis (WGCNA) based on transcriptome sequencing data from high-glucose-treated adult retinal pigment epithelial cell line-19 (ARPE-19). The chromatographic fingerprint of HF was established by ultra-performance liquid chromatography coupled with high-resolution mass spectrometry (UPLC-Q-TOF-MS). The molecular affinity of the herbal compound was measured by molecular docking. Reactive oxygen species (ROS) was measured by a DCFDA/H2DCFDA assay. Apoptosis was detected using the TUNEL Assay Kit, while ELISA, Western blot, and real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used for detecting the cytokine, protein, and mRNA expressions, respectively. Results: Key compounds in HF were identified as luteolin, paeoniflorin, and nobiletin. For WGCNA, ME-salmon ("protein deacetylation") was negatively correlated with ME-purple ("oxidative impairment") in high-glucose-treated ARPE-19. Luteolin has a high affinity for SIRT1 and P53, as indicated by molecular docking. Luteolin has a hypoglycemic effect on type I diabetic mice. Moreover, HF and luteolin suppress oxidative stress production (ROS and MDA), inflammatory factor expression (IL-6, TNF-α, IL1-ß, and MCP-1), and apoptosis, as shown in the in vivo and in vitro experiments. Concurrently, treatment with HF and luteolin led to an upregulation of SIRT1 and a corresponding downregulation of P53. Conclusion: Using HF and its active compound luteolin as therapeutic agents offers a promising approach to diabetic retinopathy treatment. It primarily suppressed protein acetylation and oxidative stress via the SIRT1/P53 pathway in retinal pigment epithelial cells.

Synergistic Strain Suppressing and Interface Engineering in Na4MnV(PO4)3/C for Wide-Temperature and Long-Calendar-Life Sodium-Ion Storage.

A Na4MnV(PO4)3 (NMVP) cathode is regarded as a promising cathode candidate for sodium-ion batteries (SIBs). However, issues such as low electronic conductivity and partial cation dissolution contribute to high polarization and structure distortion. Herein, we engineered the local electron density and reaction kinetic properties of NMVP cathodes with varying oxygen vacancies by introducing varying amounts of Zr doping and carbon coating. The optimized sample exhibited a high-rate capacity of 71.8 mAh g-1 at 30 C (83.1% capacity retention after 1000 cycles) and excellent performance over a wide temperature range (84.1 mAh g-1 at 60 °C and 61.4 mAh g-1 at -30 °C). In situ X-ray diffraction technology confirmed a redox solid solution and a two-phase reaction mechanism, revealing minor changes in cell volume and slight strain variations after Zr doping, effectively suppressing the structural distortion. Theoretical calculations illustrated that Zr doping largely shrinks the band gap of NMVP, enriches local electron density, and slightly alters the local element distribution and bond lengths. Moreover, full-cells have shown high energy density (259.9 Wh kg-1) and outstanding cycling stability (200 cycles). The work provides fresh insights into the synergistic effect of strain suppressing and interface engineering in promoting the development of wide temperature range and long-calendar-life SIBs.

Novel KMT5B variant associated with neurodevelopmental disorder in a Chinese family: A case report.

Background: We report here the clinical and genetic features of KMT5B-related neurodevelopmental disorder caused by a novel heterozygous frameshift variant in KMT5B in a Chinese family. Case presentation: A 7-year-old Chinese boy with mild-to-moderate intellectual disability, significant language impairment, motor disability, and coordination difficulties presented to our hospital because he "could not speak and did not look at others." He was diagnosed with autism spectrum disorder previously owing to developmental delays in cognition, language expression, and understanding. The child also had variable nonspecific features including macrocephaly, wide button-hole space and nasal bridge, low ear, social behavior disorder, and foot deformities. Exome sequencing (ES) revealed that both the proband and his younger brother had inherited a novel heterozygous frameshift variant c.438_439ins[ASD; KT192064.1:1_310] of the KMT5B gene from their father. Bioinformatics analysis showed that the novel mutation affected the structure of the KMT5B pre-SET domain, mainly in the α-helix region. According to the American College of Medical Genetics and Genomics (ACMG) guidelines, this type of variant was eventually determined to be likely pathogenic (PVS1+PM2_P). Conclusions: Our investigation expands the mutation spectrum of KMT5B to help us to better understand KMT5B-related neurodevelopmental disorder.

The Vitis yeshanensis U-box E3 ubiquitin ligase VyPUB21 enhances resistance to powdery mildew by targeting degradation of NIM1-interacting (NIMIN) protein.

KEY MESSAGE: VyPUB21 plays a key role during the defense against powdery mildew in grapes. Ubiquitin-ligating enzyme (E3), a type of protein widely found in plants, plays a key role in their resistance to disease. Yet how E3 participates in the disease-resistant response of Chinese wild grapevine (Vitis yeshanensis) remains unclear. Here we isolated and identified a U-box type E3 ubiquitin ligase, VyPUB21, from V. yeshanensis. This gene's expression level rose rapidly after induction by exogenous salicylic acid (SA), jasmonic acid (JA), and ethylene (ETH) and powdery mildew. In vitro ubiquitination assay results revealed VyPUB21 could produce ubiquitination bands after co-incubation with ubiquitin, ubiquitin-activating enzyme (E1), and ubiquitin-conjugating enzyme (E2); further, mutation of the conserved amino acid site in the U-box can inhibit the ubiquitination. Transgenic VyPUB21 Arabidopsis had low susceptibility to powdery mildew, and significantly fewer conidiophores and spores on its leaves. Expression levels of disease resistance-related genes were also augmented in transgenic Arabidopsis, and its SA concentration also significantly increased. VyPUB21 interacts with VyNIMIN and targets VyNIMIN protein hydrolysis through the 26S proteasome system. Thus, the repressive effect of the NIMIN-NPR complex on the late systemic acquired resistance (SAR) gene was attenuated, resulting in enhanced resistance to powdery mildew. These results indicate that VyPUB21 encoding ubiquitin ligase U-box E3 activates the SA signaling pathway, and VyPUB21 promotes the expression of late SAR gene by degrading the important protein VyNIMIN of SA signaling pathway, thus enhancing grape resistance to powdery mildew.