Investigation of the Degradation of LiPF6- in Polar Solvents through Deep Potential Molecular Dynamics.

The nonaqueous electrolyte based on lithium hexafluorophosphate (LiPF6) is the dominant liquid electrolyte in lithium-ion batteries (LIBs). However, trace protic impurities, including H3O+, alcohols, and hydrofluoric acid (HF), can trigger a series of side reactions that lead to rapid capacity fading in high energy density LIBs. It is worth noting that this degradation process is highly dependent on the polarity of the solvents. In this work, a deep potential (DP) model is trained with a certain commercial electrolyte formula through a machine learning method. H3O+ is anchored with polar solvents, making it difficult to approach the PF6-, and suppressing the degradation process quickly at room temperature. Control experiments and simulations at different temperatures or concentrations are also performed to verify it. This work proposes a precise model to describe the solvation structure quantitatively and offers a new perspective on the degradation mechanism of PF6- in polar solvents.

A novel compound heterozygous variation in the FKBP10 gene causes Bruck syndrome without congenital contractures: A case report.

Background: Bruck syndrome (BS) is an extremely rare autosomal-recessive connective tissue disorder mainly characterized by bone fragility, congenital joint contracture, and spinal deformity. It is also considered as a rare form of osteogenesis imperfecta (OI) due to features of osteopenia and fragility fractures. Its two forms, BS1 and BS2, are caused by pathogenic variations in FKBP10 and PLOD2, respectively. Objective: We aimed to improve the clinical understanding of BS by presenting a case from China and to identify the genetic variants that led to this case. Methods: OI was suspected in a Chinese boy with a history of recurrent long bone fractures, lumbar kyphosis, and dentinogenesis imperfecta (DI). Whole-exome sequencing (WES) was performed to identify pathogenic variations. Sanger sequencing was used to confirm the results of the WES. In silico analysis was used to predict the pathogenicity of genetic variants. Results: WES and Sanger sequencing revealed a compound heterozygous variation in the FKBP10 gene (NM_021939, c.23dupG in exon 1, and c.825dupC in exon 5). Both variants resulted in a frameshift and premature stop codon. Of these two variants, c.23dupG has not been previously reported. The patient's parents were heterozygous carriers of one variant. In addition, zoledronic acid treatment improved the vertebral deformity and bone mineral density (BMD) significantly in this patient. Conclusions: A novel compound heterozygous variation of FKBP10, c.23dupG/c.825dupC, was identified in a patient with moderately severe OI. Based on these findings, the patient was diagnosed with BS1 without congenital joint contractures or OI type XI. This study expands the spectrum of FKBP10 genetic variants that cause BS and OI.

Observer-based event-triggered H∞ control for Hamiltonian systems.

This paper investigates the problem of designing an observer-based event-triggered H∞ controller for a Hamiltonian system with delays incorporated in the underlying network. As our contributions, we first propose an event-triggered scheme which uses the Hamiltonian to decide whether to trigger the event generator at the sampling time. Additionally, when states are not exactly known globally asymptotically stable, we proceed to design an observer-based controller with which the resulting closed-loop system can be transformed into a time-delay Hamiltonian system. Based on the structural characteristic of the Hamiltonian systems, sufficient conditions are given to guarantee the closed-loop system to achieve the H∞ performance index with external disturbances in available and unavailable states, respectively. Finally, multi-machine power systems as simulation examples are illustrated to validate our proposed results.

Why the Synthesis Affects Performance of Layered Transition Metal Oxide Cathode Materials for Li-Ion Batteries.

The limited cyclability of high-specific-energy layered transition metal oxide (LiTMO2) cathode materials poses a significant challenge to the industrialization of batteries incorporating these materials. This limitation can be attributed to various factors, with the intrinsic behavior of the crystal structure during the cycle process being a key contributor. These factors include phase transition induced cracks, reduced Li active sites due to Li/Ni mixing, and slower Li+ migration. In addition, the presence of synthesis-induced heterogeneous phases and lattice defects cannot be disregarded as they also contribute to the degradation in performance. Therefore, gaining a profound understanding of the intricate relationship among material synthesis, structure, and performance is imperative for the development of LiTMO2. This paper highlights the pivotal role of structural play in LiTMO2 materials and provides a comprehensive overview of how various control factors influence the specific pathways of structural evolution during the synthesis process. In addition, it summarizes the scientific challenges associated with diverse modification approaches currently employed to address the cyclic failure of materials. The overarching goal is to provide readers with profound insights into the study of LiTMO2.

Ultrahigh-printing-speed photoresists for additive manufacturing.

Printing technology for precise additive manufacturing at the nanoscale currently relies on two-photon lithography. Although this methodology can overcome the Rayleigh limit to achieve nanoscale structures, it still operates at too slow of a speed for large-scale practical applications. Here we show an extremely sensitive zirconium oxide hybrid-(2,4-bis(trichloromethyl)-6-(4-methoxystyryl)-1,3,5-triazine) (ZrO2-BTMST) photoresist system that can achieve a printing speed of 7.77 m s-1, which is between three and five orders of magnitude faster than conventional polymer-based photoresists. We build a polygon laser scanner-based two-photon lithography machine with a linear stepping speed approaching 10 m s-1. Using the ZrO2-BTMST photoresist, we fabricate a square raster with an area of 1 cm2 in ~33 min. Furthermore, the extremely small chemical components of the ZrO2-BTMST photoresist enable high-precision patterning, leading to a line width as small as 38 nm. Calculations assisted by characterizations reveal that the unusual sensitivity arises from an efficient light-induced polarity change of the ZrO2 hybrid. We envisage that the exceptional sensitivity of our organic-inorganic hybrid photoresist may lead to a viable large-scale additive manufacturing nanofabrication technology.

Charge Shielding-Oriented Design of Zinc-Based Nanoparticle Liquids for Controlled Nanofabrication.

Metal-containing nanoparticles possess nanoscale sizes, but the exploitation of their nanofeatures in nanofabrication processes remains challenging. Herein, we report the realization of a class of zinc-based nanoparticle liquids and their potential for applications in controlled nanofabrication. Utilizing the metal-core charge shielding strategy, we prepared nanoparticles that display glass-to-liquid transition behavior with glass transition temperature far below room temperature (down to -50.9 °C). Theoretical calculations suggest the outer surface of these unusual nanoparticles is almost neutral, thus leading to interparticle interactions weak enough to give them liquefaction characteristics. Such features endow them with extraordinarily high dispersibility and excellent film-forming capabilities. Twenty-two types of nanoparticles synthesized by this strategy have all shown good lithographic properties in the mid-ultraviolet, electron beam, or extreme ultraviolet light, and these nanoparticle liquids have achieved controlled top-down nanofabrication with predesigned 18 or 16 nm patterns. This proposed strategy is synthetically scalable and structurally extensible and is expected to inspire the design of entirely new forms of nanomaterials.

NR1 Splicing Variant NR1a in Cerebellar Granule Neurons Constitutes a Better Motor Learning in the Mouse.

As an excitatory neuron in the cerebellum, the granule cells play a crucial role in motor learning. The assembly of NMDAR in these neurons varies in developmental stages, while the significance of this variety is still not clear. In this study, we found that motor training could specially upregulate the expression level of NR1a, a splicing form of NR1 subunit. Interestingly, overexpression of this splicing variant in a cerebellar granule cell-specific manner dramatically elevated the NMDAR binding activity. Furthermore, the NR1a transgenic mice did not only show an enhanced motor learning, but also exhibit a higher efficacy for motor training in motor learning. Our results suggested that as a "junior" receptor, NR1a facilitates NMDAR activity as well as motor skill learning.

A novel mutation in intron 1 of Wnt1 causes developmental loss of dopaminergic neurons in midbrain and ASD-like behaviors in rats.

Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders with a strong genetic liability. Despite extensive studies, however, the underlying pathogenic mechanism still remains elusive. In the present study, we identified a homozygous mutation in the intron 1 of Wnt1 via large-scale screening of ASD risk/causative genes and verified that this mutation created a new splicing donor site in the intron 1, and consequently, a decrease of WNT1 expression. Interestingly, humanized rat models harboring this mutation exhibited robust ASD-like behaviors including impaired ultrasonic vocalization (USV), decreased social interactions, and restricted and repetitive behaviors. Moreover, in the substantia nigra compacta (SNpc) and the ventral tegmental area (VTA) of mutant rats, dopaminergic (DAergic) neurons were dramatically lost, together with a comparable decrease in striatal DAergic fibers. Furthermore, using single-cell RNA sequencing, we demonstrated that the decreased DAergic neurons in these midbrain areas might attribute to a shift of the boundary of the local pool of progenitor cells from the hypothalamic floor plate to the midbrain floor plate during the early embryonic stage. Moreover, treatments of mutant rats with levodopa could attenuate the impaired USV and social interactions almost completely, but not the restricted and repetitive behaviors. Our results for the first time documented that the developmental loss of DAergic neurons in the midbrain underlies the pathogenesis of ASD, and that the abnormal progenitor cell patterning is a cellular underpinning for this developmental DAergic neuronal loss. Importantly, the effective dopamine therapy suggests a translational significance in the treatment of ASD.

Iridium-Catalyzed Diastereo- and Enantioselective [4 + 1] Cycloaddition of Hydroxyallyl Anilines with Sulfoxonium Ylides.

We present here an iridium-catalyzed diastereo- and enantioselective [4 + 1] cycloaddition reaction of hydroxyallyl anilines with sulfoxonium ylides under mild reaction conditions, leading to 3-vinyl indolines in moderate to good yields with excellent enantioselectivities. Control experiments disclosed a plausible reaction mechanism.

Cataract-causing Y204X mutation of crystallin protein CRYßB1 promotes its C-terminal degradation and higher-order oligomerization.

Crystallin proteins are a class of main structural proteins of the vertebrate eye lens, and their solubility and stability directly determine transparency and refractive power of the lens. Mutation in genes that encode these crystallin proteins is the most common cause for congenital cataracts. Despite extensive studies, the pathogenic and molecular mechanisms that effect congenital cataracts remain unclear. In this study, we identified a novel mutation in CRYBB1 from a congenital cataract family, and demonstrated that this mutation led to an early termination of mRNA translation, resulting in a 49-residue C-terminally truncated CRYßB1 protein. We show this mutant is susceptible to proteolysis, which allowed us to determine a 1.2-Å resolution crystal structure of CRYßB1 without the entire C-terminal domain. In this crystal lattice, we observed that two N-terminal domain monomers form a dimer that structurally resembles the WT monomer, but with different surface characteristics. Biochemical analyses and cell-based data also suggested that this mutant is significantly more liable to aggregate and degrade compared to WT CRYßB1. Taken together, our results provide an insight into the mechanism regarding how a mutant crystalin contributes to the development of congenital cataract possibly through alteration of inter-protein interactions that result in protein aggregation.

Converting Nafion into Li+ -Conductive Nanoporous Materials.

Sulfonated polymers have long been used as proton-conducting materials in fuel cells, and their ionic transport features are highly attractive for electrolytes in lithium-ion/metal batteries (LIBs/LMBs). However, most studies are still based on a preconceived notion of using them directly as polymeric ionic carriers, which precludes exploring them as nanoporous media to construct efficient lithium ions (Li+ ) transport network. Here, effective Li+ -conducting channels realized by swelling nanofibrous Nafion is demonstrated, which is a classical sulfonated polymer in fuel cells. The sulfonic acid groups, interact with LIBs liquid electrolytes to form porous ionic matrix of Nafion and assist partial desolvation of Li+ -solvates to further enhance Li+ transport. Li-symmetric cells and Li-metal full cells (Li4 Ti5 O12 or high-voltage LiNi0.6 Co0.2 Mn0.2 O2 as a cathode) with such membrane show excellent cycling performance and stabilized Li-metal anode. The finding provides a strategy to convert the vast sulfonated polymer family into efficient Li+ electrolyte, promoting the development of high-energy-density LMBs.

Exosomes-delivered PD-L1 siRNA and CTLA-4 siRNA protect against growth and tumor immune escape in colorectal cancer.

OBJECTIVE: This study aims to dissect impacts of exosomes-delivered PD-L1 and CTLA-4 siRNAs on colorectal cancer (CRC) progression and immune responses. METHODS: Exosomes containing PD-L1 siRNA and CTLA-4 siRNA were prepared and utilized to treat CRC cells to evaluate their effects. A tumor-bearing mouse model was established for verification. RESULTS: Exosomes containing PD-L1 siRNA and CTLA-4 siRNA repressed malignant features of CRC cells and restrained tumor growth and activated tumor immune responses in vivo. Co-culture of CRC cells treated with exosomes containing PD-L1 siRNA and CTLA-4 siRNA with human CD8+ T cells increased the percentage of CD8+ T cells, decreased the apoptotic rate of CD8+ T cells, elevated IL-2, IFN-γ, and TNF-α expression in cell supernatants, reduced adherent density of CRC cells, augmented the positive rate of CRC cells, and subdued tumor immune escape. CONCLUSION: Exosomes containing PD-L1 siRNA and CTLA-4 siRNA suppressed CRC progression and enhanced tumor immune responses.

SlZF3 regulates tomato plant height by directly repressing SlGA20ox4 in the gibberellic acid biosynthesis pathway.

Plant height is an important target trait for crop genetic improvement. Our previous work has identified a salt-tolerant C2H2 zinc finger, SlZF3, and its overexpression lines also showed a semi-dwarf phenotype, but the molecular mechanism remains to be elucidated. Here, we characterized the dwarf phenotype in detail. The dwarfism is caused by a decrease in stem internode cell elongation and deficiency of bioactive gibberellic acids (GAs), and can be rescued by exogenous GA3 treatment. Gene expression assays detected reduced expression of genes in the GA biosynthesis pathway of the overexpression lines, including SlGA20ox4. Several protein-DNA interaction methods confirmed that SlZF3 can directly bind to the SlGA20ox4 promoter and inhibit its expression, and the interaction can also occur for SlKS and SlKO. Overexpression of SlGA20ox4 in the SlZF3-overexpressing line can recover the dwarf phenotype. Therefore, SlZF3 regulates plant height by directly repressing genes in the tomato GA biosynthesis pathway.

Impact of age on short-term outcomes after pancreaticoduodenectomy: A retrospective case-control study of 260 patients.

Background: Although the increase of perioperative complications in the elderly undergoing pancreaticoduodenectomy (PD) surgery has been recognized, the definition of the "old patient" of PD in the studies is different and there is no accepted cut-off value at present. Methods: 279 consecutive patients who have undergone PD in our center between January 2012 and May 2020 were analyzed. Demographic features, clinical-pathological data and short-term outcomes were collected. The patients were divided into two groups, and the cut-off value (62.5 years) is picked based on the highest Youden Index. Primary endpoints were perioperative morbidity and mortality, and complications were classified according to the Clavien-Dindo Score. Results: A total of 260 patients with PD were included in this study. Postoperative pathology confirmed pancreatic tumors in 62 patients, bile duct tumor in 105, duodenal tumor in 90, and others in 3. Age (OR = 1.09, P < 0.01), and albumin (OR = 0.34, P < 0.05) were significantly correlated with postoperative Clavien-Dindo Score ≥3b. There were 173 (66.5%) patients in the younger group (<62.5 years) and 87 (33.5%) in the elderly group (≥62.5 years). Significant difference between two groups was demonstrated for Clavien-Dindo Score ≥3b (P < 0.01), postoperative pancreatic fistula (P < 0.05), and perioperative deceases (P < 0.05). Conclusions: Age and albumin were significantly correlated with postoperative Clavien-Dindo Score ≥3b, and there was no significant difference in predicting the grade of Clavien-Dindo Score. The cut-off value of elderly patients with PD was 62.5 years old and there were useful in predicting Clavien-Dindo Score ≥3b, pancreatic fistula, and perioperative death.

Transcriptomics and Metabolomics Analysis Provides Insight into Leaf Color and Photosynthesis Variation of the Yellow-Green Leaf Mutant of Hami Melon (Cucumis melo L.).

Leaf color mutants are ideal materials for studying the regulatory mechanism of chloroplast development and photosynthesis. We isolated a cucumis melo spontaneous mutant (MT), which showed yellow-green leaf phenotype in the whole growing period and could be inherited stably. We compared its leaves with the wild type (WT) in terms of cytology, physiology, transcriptome and metabolism. The results showed that the thylakoid grana lamellae of MT were loosely arranged and fewer in number than WT. Physiological experiments also showed that MT had less chlorophyll content and more accumulation of reactive oxygen species (ROS) than WT. Furthermore, the activity of several key enzymes in C4 photosynthetic carbon assimilation pathway was more enhanced in MT than WT. Transcriptomic and metabolomic analyses showed that differential expression genes and differentially accumulated metabolites in MT were mainly co-enriched in the pathways related to photosystem-antenna proteins, central carbon metabolism, glutathione metabolism, phenylpropanoid biosynthesis and flavonoid metabolism. We also analyzed several key proteins in photosynthesis and chloroplast transport by Western blot. In summary, the results may provide a new insight into the understanding of how plants respond to the impaired photosynthesis by regulating chloroplast development and photosynthetic carbon assimilation pathways.

Super-pangenome analyses highlight genomic diversity and structural variation across wild and cultivated tomato species.

Effective utilization of wild relatives is key to overcoming challenges in genetic improvement of cultivated tomato, which has a narrow genetic basis; however, current efforts to decipher high-quality genomes for tomato wild species are insufficient. Here, we report chromosome-scale tomato genomes from nine wild species and two cultivated accessions, representative of Solanum section Lycopersicon, the tomato clade. Together with two previously released genomes, we elucidate the phylogeny of Lycopersicon and construct a section-wide gene repertoire. We reveal the landscape of structural variants and provide entry to the genomic diversity among tomato wild relatives, enabling the discovery of a wild tomato gene with the potential to increase yields of modern cultivated tomatoes. Construction of a graph-based genome enables structural-variant-based genome-wide association studies, identifying numerous signals associated with tomato flavor-related traits and fruit metabolites. The tomato super-pangenome resources will expedite biological studies and breeding of this globally important crop.

The mechanisms underlying the enrichment and action of glypican-1-positive exosomes in colorectal cancer cells.

BACKGROUND: Glypican-1 (GPC1) is overexpressed in several tumors, and GPC1+ exosomes have shown the potential to predict early colorectal cancer (CRC). However, the mechanisms underlying the enrichment and action of GPC1+ exosomes in CRC remain unknown. METHODS: The expression of slit guidance ligand 2 (SLIT2), hypoxia-inducible factor (HIF)-1α/2α, and GPC1 in clinical CRC tissues was detected using immunohistochemistry and western blot. Exosomes were isolated from the supernatants of CRC cell cultures. The effects of SLIT2, hypoxia, heparin, and phospholipase C (PLC) on exosomal GPC1 expression and GPC1+ exosome enrichment in CRC cells were analyzed with western blot and flow cytometry. CRC cell proliferation was assessed with MTT and colony formation assays. Co-immunoprecipitation was used to detect the binding of GPC1 and SLIT2 in SW480 cells. Nude mice were subcutaneously inoculated with SW480 cells with different treatments. The Wnt signaling was detected. RESULTS: SLIT2 was poorly expressed and GPC1, HIF-1α, and HIF-2α were highly expressed in human CRC tissues. SLIT2 in CRC cells inhibited GPC1+ exosome enrichment and exosomal GPC1 expression. PLC and heparin increased GPC1+ exosome enrichment in CRC cells in a concentration-dependent manner. Hypoxia increased the enrichment of GPC1+ exosomes in CRC cells depending on HIF-2α expression. GPC1+ exosomes stimulated CRC cell proliferation and xenograft tumor growth through activation of Wnt signaling. CONCLUSIONS: GPC1+ exosome enrichment is related to PLC and heparin. Hypoxia increases the enrichment of GPC1+ exosomes in CRC cells by activating HIF-2α and downregulating SLIT2. GPC1+ exosomes further drive CRC progression by activating Wnt signaling.

Iron overload facilitates neonatal hypoxic-ischemic brain damage via SLC7A11-mediated ferroptosis.

Oxidative damage and cell death are involved in the pathogenesis of hypoxic-ischemic brain damage (HIBD). Ferroptosis is a newly identified mode of cell death that results from the oxidative damage induced by excessive iron. In HIBD, iron accumulates in brain tissues due to the massive destruction of red blood cells and increased permeability of the blood brain barrier vasculature, which can trigger ferroptosis. Ferroptosis is implicated in various diseases involving neuronal injury; however, the roles of iron and ferroptosis in HIBD have not been identified. In the present study, we investigated the role of iron overload in neuronal ferroptosis both in HIBD rat models and in oxygen- and glucose-deprived (OGD) SH-SY5Y cells. We observed that iron deposition in the cerebral cortex was significantly increased in HIBD rats. Features of ferroptosis such as shrunken mitochondria, increased MDA (malondialdehyde) levels, and reduced solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) expression were observed in the cerebral cortex of HIBD rats. Administration of an iron chelator in HIBD rats upregulated SLC7A11 expression and alleviated neuronal ferroptosis in cerebral cortex tissue. Additionally, overexpression of SLC7A11 in SH-SY5Y cells increased cell viability and attenuated OGD-induced ferroptosis. Our results demonstrate that iron overload induces neuronal ferroptosis by inhibiting SLC7A11 expression in HIBD. Inhibition of neuronal ferroptosis may be a promising strategy to alleviate brain damage in HIBD.

A Protophilic MOF Enables Ni-Rich Lithium-Battery Stable Cycling in a High Water/Acid Content.

Trace protic impurities, such as water and hydrofluoric acid (HF), can severely degrade the stable and long cycling of lithium batteries. Therefore, the costly water removal process is inevitably needed throughout production of lithium batteries, leaving the paradox that energy-saving lithium-battery technology consumes non-negligible amounts of energy. Herein, a unique ionic metal-organic framework (MOF) is reported that enables highly destructive H2 O/HF-tolerant lithium batteries. The isolated ionic fluorine sites in the MOF exhibit unusual protophilicity and efficiently capture ppm-levels H2 O/HF from the highly polar electrolyte solvents. The resulting MOF-based LiNi0.6 Mn0.2 Co0.2 O2 │Li battery achieves over 300 cycles in the presence of 800 ppm H2 O or 1107 ppm acidic impurity. This tenfold longer battery lifespan relative to those for batteries with conventional standard separators demonstrates its excellent electrochemical cycling performance. The results reveal that the rational use of unique nanoporous features of MOFs can provide new possibilities for long-standing challenges in the lithium-battery industry.

Human cytomegalovirus infection perturbs neural progenitor cell fate via the expression of viral microRNAs.

Human cytomegalovirus (HCMV) preferentially targets neural progenitor cells (NPCs) in congenitally infected fetal brains, inducing neurodevelopmental disorders. While HCMV expresses several microRNAs (miRNAs) during infection, their roles in NPC infection are unclear. Here, we characterized expression of cellular and viral miRNAs in HCMV-infected NPCs during early infection by microarray and identified seven differentially expressed cellular miRNAs and six significantly upregulated HCMV miRNAs. Deep learning approaches were used to identify potential targets of significantly upregulated HCMV miRNAs against differentially expressed cellular messenger RNA (mRNAs), and the associations with miRNA-mRNA expression changes were observed. Gene ontology enrichment analysis indicated cellular gene targets were significantly enriched in pathways involved in neurodevelopment and cell-cycle processes. Viral modulation of selected miRNAs and cellular gene targets involved in neurodevelopmental processes were further validated by real-time quantitative reverse transcription polymerase chain reaction. Finally, a predicted 3' untranslated region target site of hcmv-miR-US25-1 in Jag1, a factor important for neurogenesis, was confirmed by mutagenesis. Reduction of Jag1 RNA and protein levels in NPCs was observed in response to transient expression of hcmv-miR-US25-1. A hcmv-miR-US25-1 mutant virus (ΔmiR-US25) displayed limited ability to downregulate Jag1 mRNA levels and protein levels during the early infection stage compared with the wild type virus. Our collective experimental and computational investigation of miRNAs and cellular mRNAs expression in HCMV-infected NPCs yields new insights into the roles of viral miRNAs in regulating NPC fate and their contributions to HCMV neuropathogenesis.