[Human tau N-terminal domain-specific monoclonal antibodies: screening and application in blood detection].

The antibodies to the microtubule-associated protein tau play a role in basic and clinical studies of Alzheimer's disease (AD) and other tauopathies. With the recombinant human tau441 as the immunogen, the hybridoma cell strains secreting the anti-human tau N-terminal domain (NTD-tau) monoclonal antibodies were generated by cell fusion and screened by limiting dilution. The purified monoclonal antibodies were obtained by inducing the mouse ascites and affinity chromatography. The sensitivity and specificity of the monoclonal antibodies were examined by indirect ELISA and Western blotting, respectively. A double antibody sandwich ELISA method for detecting human tau protein was established and optimized. The results showed that the positive cloning rate of hybridoma cells was 83.6%. A stable cell line producing ZD8F7 antibodies was established, and the antibody titer in the supernatant of the cell line was 1:16 000. The antibody titer in the ascitic fluid was higher than 1:256 000; and the titer of purified ZD8F7 monoclonal antibodies was higher than 1:128 000. The epitope analysis showed that the ZD8F7 antibody recognized tau21-37 amino acid in the N-terminal domain. The Western blotting results showed that the ZD8F7 antibody recognized the recombinant human tau protein of 50-70 kDa and the human tau protein of 50 kDa in the brain tissue of transgenic AD model mice (APP/PS1/tau). With ZD8F7 as a capture antibody, a quantitative detection method for human tau protein was established, which showed a linear range of 7.8-500.0 pg/mL and could identify human tau protein in the brain tissue of AD transgenic mice and human plasma but not recognize the mouse tau protein. In conclusion, the human NTD-tau-specific monoclonal antibody and the double antibody sandwich ELISA method established in this study are highly sensitive and can serve as a powerful tool for the detection of tau protein in neurodegenerative diseases.

Organizing Photosensitive and Photothermal Single-Sites Uniformly in a Trimetallic Metal-Organic Framework for Efficient Photocatalytic Hydrogen Evolution.

Effective combination of the photosensitivity and photothermal property in photocatalyst is vital to achieve the maximum light utilization for superior photocatalytic efficiency. Herein, this work successfully organizes photosensitive Cd-NS single-sites and photothermal Ni-NS single-sites uniformly at a molecular level within a tailored trimetallic metal-organic framework. The optimized Ho6-Cd0.76Ni0.24-NS exhibits a superior photocatalytic hydrogen evolution rate of 40.06 mmol g-1 h-1 under visible-light irradiation and an apparent quantum efficiency of 29.37% at 420 nm without using cocatalysts or photosensitizers. A systematical mechanism study reveals that the uniformly organized photosensitive and photothermal single-sites have synergistic effect, which form ultrashort pathways for efficient transport of photoinduced electrons, suppress the recombination of photogenerated charge carriers, hence promote the hydrogen evolution activity. This work provides a promising approach for organizing dual-functional single-sites uniformly in photocatalyst for high-performance photocatalytic activity.

Boosting the Lithium-Ion Transport Kinetics of Sn-Based Coordination Polymers through Ligand Aromaticity Manipulation.

Tin-based compounds are promising anode materials for lithium-ion batteries owing to their low charge/discharge voltage and high theoretical capacity but are plagued by both huge volume expansion during cycling and complex synthetic procedures. Constructing a coordination network between Sn and the lithium-active organic matrix can effectively relieve the volume expansion and increase the lithium storage active site utilization. Herein, we report a facile method to prepare two one-dimensional Sn-based coordination polymers [Sn(Hcta)]n (1) and [Sn(Hbtc)]n (2) (H3cta = 1,3,5-cyclohexanetricarboxylic acid, H3btc = 1,3,5-benzenetricarboxylic acid) for lithium storage, which differ only in the aromaticity of the ligand. 2 with an aromatic ligand provided a reversible capacity of 833 mAh g-1 at 200 mA g-1 over 160 cycles, higher than that of 1 without an aromatic ligand due to the quick charge transfer. The reversible lithium storage reactions of metal centers and organic ligands and the volume expansion rate of Sn-based coordination polymers during cycling were studied by detailed characterization and density functional theory (DFT) calculations. This research revealed that the structural factor of ligand aromaticity in these Sn-based coordination polymers boosted the utilization of active sites and rapid charge transfer, offering a coordination chemistry strategy for the design and synthesis of advanced anode materials.

Promoted Photocatalytic Hydrogen Evolution by Tuning the Electronic State of Copper Sites in Metal-Organic Supramolecular Assemblies.

The electronic state in terms of charge and spin of metal sites is fundamental to govern the catalytic activity of a photocatalyst. Herein, we show that modulation of the electronic states of Cu sites, without changing the coordination environments, of two metal-organic supramolecular assemblies based on π⋅⋅⋅π stacking can significantly improve photocatalytic activity. The use of these heterogeneous photocatalysts, without using noble metal cocatalysts, resulted in an increase of the hydrogen production rate from 522 to 3620 µmol h-1 g-1 . A systematical analysis revealed that the charge density and spin density of the metal centers are efficiently modulated via the modulation of the coordination fields around active copper (II) centers by the variation of the non-coordination groups of terminal ligands, leading to the significant enhancement of photocatalytic activity. This work provides an insight into the electronic state of active metal centers for designing high-performance photocatalysts.

Hydrogen-bonded Complex-based Frameworks for Stable Lithium Storage.

Metal-complex-based materials for lithium storage have attracted great interest due to their highly designable structures with multiple active sites and well-defined lithium transport pathways. Their cycling and rate performances, however, are still constrained by structural stability and electrical conductivity. Herein, we present two hydrogen-bonded complex-based frameworks with excellent lithium storage capability. Multiple hydrogen bonds among the mononuclear molecules result in three-dimensional frameworks that are stable in electrolyte. The origin of the remarkable lithium storage performance of this family was revealed through kinetic analysis and DFT calculations.

D-SPIN constructs gene regulatory network models from multiplexed scRNA-seq data revealing organizing principles of cellular perturbation response.

Gene regulatory networks within cells modulate the expression of the genome in response to signals and changing environmental conditions. Reconstructions of gene regulatory networks can reveal the information processing and control principles used by cells to maintain homeostasis and execute cell-state transitions. Here, we introduce a computational framework, D-SPIN, that generates quantitative models of gene-regulatory networks from single-cell mRNA-seq data sets collected across thousands of distinct perturbation conditions. D-SPIN models the cell as a collection of interacting gene-expression programs, and constructs a probabilistic model to infer regulatory interactions between gene-expression programs and external perturbations. Using large Perturb-seq and drug-response datasets, we demonstrate that D-SPIN models reveal the organization of cellular pathways, sub-functions of macromolecular complexes, and the logic of cellular regulation of transcription, translation, metabolism, and protein degradation in response to gene knockdown perturbations. D-SPIN can also be applied to dissect drug response mechanisms in heterogeneous cell populations, elucidating how combinations of immunomodulatory drugs can induce novel cell states through additive recruitment of gene expression programs. D-SPIN provides a computational framework for constructing interpretable models of gene-regulatory networks to reveal principles of cellular information processing and physiological control.

High-Efficiency Lithium-Ion Transport in a Porous Coordination Chain-Based Hydrogen-Bonded Framework.

Fast and selective Li+ transport in solid plays a key role for the development of high-performance solid-state electrolytes (SSEs) of lithium metal batteries. Porous compounds with tunable Li+ transport pathways are promising SSEs, but the comprehensive performances in terms of Li+ transport kinetics, electrochemical stability window, and interfacial compatibility are difficult to be achieved simultaneously. Herein, we report a porous coordination chain-based hydrogen-bonded framework (NKU-1000) containing arrayed electronegative sites for Li+ transport, exhibiting a superior Li+ conductivity of 1.13 × 10-3 S cm-1, a high Li+ transfer number of 0.87, and a wide electrochemical window of 5.0 V. The assembled solid-state battery with NKU-1000-based SSE shows a high discharge capacity with 94.4% retention after 500 cycles and can work over a wide temperature range without formation of lithium dendrites, which derives from the linear hopping sites that promote a uniformly high-rate Li+ flux and the flexible structure that can buffer the structural variation during Li+ transport.

Construction of a High-Density Recombination Bin-Based Genetic Map Facilitates High-Resolution Mapping of a Major QTL Underlying Anthocyanin Pigmentation in Eggplant.

High-density genetic maps can significantly improve the resolution of QTL mapping. We constructed a high-density recombination bin-based genetic map of eggplant based on 200 F2 plants from an interspecific cross (Solanum melongena × S. incanum) using the whole genome resequencing strategy. The map was 2022.8 cM long, covering near 99% of the eggplant genome. The map contained 3776 bins, with 3644 (96.5%) being effective (position non-redundant) ones, giving a nominal average distance of 0.54 cM and an effective average distance of 0.56 cM between adjacent bins, respectively. Using this map and 172 F2:3 lines, a major QTL with pleiotropic effects on two anthocyanin pigmentation-related traits, leaf vein color (LVC) and fruit pericarp color (FPC), was steadily detected in a bin interval of 2.28 cM (or 1.68 Mb) on chromosome E10 in two cropping seasons, explaining ~65% and 55% of the phenotypic variation in LVC and FPC, respectively. Genome-wide association analysis in this population validated the QTL and demonstrated the correctness of mapping two bins of chromosome E02 onto E10. Bioinformatics analysis suggested that a WDR protein gene inside the bin interval with reliable effective variation between the two parents could be a possible candidate gene of the QTL.

A case report: Anesthetic management for open-heart surgery in a child with congenital insensitivity to pain with anhidrosis.

Congenital insensitivity to pain with anhidrosis (CIPA) is a rare disease also known as hereditary sensory and autonomic neuropathy. CIPA is characterized by a lack of pain sensitivity and impaired development of sweat glands. Surgery is required for patients with self-mutilation and skeletal developmental disorders. Due to the disease's rarity and intricacy, anesthesia poses its challenges. Although there have been a few cases of CIPA patients receiving surgery and anesthesia, the number is very limited. Here, we report a case of a child with CIPA who underwent open-heart surgery and discuss the anesthetic considerations. We conclude that patients with CIPA undergoing open-heart surgery require some opioids, that muscle relaxants and volatile anesthetics should be used with extreme caution, and that airway management and temperature control require special attention.

A Zinc-Dual-Halogen Battery with a Molten Hydrate Electrolyte.

Halogen redox couples offer several advantages for energy storage such as low cost, high solubility in water, and high redox potential. However, the operational complexity of storing halogens at the oxidation state via liquid-phase media hampers their widespread application in energy-storage devices. Herein, an aqueous zinc-dual-halogen battery system taking the advantages of redox flow batteries (inherent scalability) and intercalation chemistry (high capacity) is designed and fabricated. To enhance specific energy, the designed cell exploits both bromine and chlorine as the cathode redox couples that are present as halozinc complexes in a newly developed molten hydrate electrolyte, which is distinctive to the conventional zinc-bromine batteries. Benefiting from the reversible uptake of halogens at the graphite cathode, exclusive reliance on earth-abundant elements, and membrane-free and possible flow-through configuration, the proposed battery can potentially realize high-performance massive electric energy storage at a reasonable cost.

The dynamic transmission of positional information in stau- mutants during Drosophila embryogenesis.

It has been suggested that Staufen (Stau) is key in controlling the variability of the posterior boundary of the Hb anterior domain (xHb). However, the mechanism that underlies this control is elusive. Here, we quantified the dynamic 3D expression of segmentation genes in Drosophila embryos. With improved control of measurement errors, we show that the xHb of stau- mutants reproducibly moves posteriorly by 10% of the embryo length (EL) to the wild type (WT) position in the nuclear cycle (nc) 14, and that its variability over short time windows is comparable to that of the WT. Moreover, for stau- mutants, the upstream Bicoid (Bcd) gradients show equivalent relative intensity noise to that of the WT in nc12-nc14, and the downstream Even-skipped (Eve) and cephalic furrow (CF) show the same positional errors as these factors in WT. Our results indicate that threshold-dependent activation and self-organized filtering are not mutually exclusive and could both be implemented in early Drosophila embryogenesis.

Broadly speaking, all individuals of any animal species share a highly consistent shape and structure. Despite this, the activity of the genes that control these body patterns can vary significantly. There are currently two models that have been proposed for how noisy systems of genes, and the proteins they code, can produce consistent body patterns. The first, suggests the noise is essentially self-compensating so stably produces the same result, while the second invokes localized self-organizing systems that help to refine the structural details. In the early stages of development for the fruit fly, Drosophila melanogaster, one of the proteins that controls body patterns is called Hunchback (often just Hb for short). The Hb proteins are largely found at the front-end of the fly embryo, with a sharp drop near the middle. Normally the position of the drop in Hb varies between flies by around 1% of the total length of the fly embryo. Previous work has linked a gene called staufan (or stau for short) to the distribution of Hb in flies but the mechanism involved is unknown. Yang, Zhu, Kong et al. have now used a technique called light sheet microscopy to accurately measure the location of Hb proteins in fruit fly embryos. Without the stau gene, the average position of the drop in Hb proteins underwent a larger shift towards the rear at a key stage in development. Despite this altered behavior, the extent of variation between flies did not change. Similarly, the variation of other genes that control Hb location and that are controlled by Hb remained unchanged. As such, it seems stau affects Hb positioning but has no impact on variation between individuals. These findings suggest that both models for controlling variation in fly development could still be relevant and may operate together. This study also provides a new method for the more precise measurement of systems like these that may offer insights into the mechanisms involved in early embryonic development.

MicroRNA-375 inhibits esophageal squamous cell carcinoma proliferation through direct targeting of SP1.

Several studies have shown that microRNA-375 (miR-375) is frequently downregulated in several types of human cancer including gastric cancer, colorectal cancer and oral squamous cell carcinoma. However, the role of miR-375 in human esophageal cancer remains unknown. In the current study, the expression level of miR-375 was analyzed in 43 esophageal squamous cell carcinoma (ESCC) tissue and matched adjacent normal tissue samples from patients with ESCC by reverse transcription-quantitative polymerase chain reaction. In addition, the expression level of miR-375 was analyzed in ESCC cell lines (KYSE450 and KYSE150) and the human esophageal epithelial cell line Het-1A by the same method. The expression level of miR-375 was significantly downregulated in ESCC tissue samples and cell lines compared with adjacent normal tissue samples and the human esophageal epithelial cell line, respectively. The effect of miR-375 on ESCC cell proliferation was detected by cell counting kit-8 (CCK-8) and colony formation assays. miR-375 overexpression significantly decreased ESCC cell proliferation and colony formation. Bioinformatics analysis was used to predict specificity protein 1 (SP1) as a target gene of miR-375 in ESCC, and this was verified by dual-luciferase assay. The present study demonstrated that SP1 regulates ESCC cell proliferation and colony formation through direct interaction with miR-375. In addition, the overall survival of patients with ESCC was analyzed using the Kaplan-Meier method and log-rank test. The results indicated that patients with ESCC with high miR-375 expression had a better survival rate compared with patients with ESCC with low miR-375 expression. Taken together, these results suggest that downregulated miR-375 promotes ESCC cell proliferation and colony formation via direct targeting of SP1, and this association may contribute to ESCC progression.

Potential neurotoxicity of prenatal exposure to sevoflurane on offspring: Metabolomics investigation on neurodevelopment and underlying mechanism.

Repeated or prolonged anesthesia to pregnant women disturbs neurodevelopment of developing infants, but its mechanism has not been elaborated absolutely. This study was conducted to investigate the mechanism of potential neurotoxicity on their offspring generation after sevoflurane anesthesia in adult animals during pregnancy based on metabolomics. 16 pregnant rats were equally assigned to sevoflurane group and control group, and serum samples were collected from their 7-day-old offspring for metabolomics analysis using ultra performance liquid chromatography coupled to time-of-flight mass spectrometry. Principal component analysis and partial least squares-discriminate analysis were used for pattern recognition, and pathway analysis was performed by MetaboAnalyst platform. 29 metabolites were discovered as neurotoxicity related-biomarkers, among which S-Adenosylmethioninamine was inhibited dramatically after sevoflurane exposure. Prenatal exposure to sevoflurane led to a significant reduction in S-Adenosylmethionine level, as shown by enzyme-linked immunosorbent assay. Pathway analysis highlighted that prenatal exposure to sevoflurane induced alteration in arginine/proline metabolism, cysteine/methionine metabolism, and so on. The most important altered metabolic pathway was arginine/proline metabolism. This study suggests that abnormal methylation and disturbed arginine/proline metabolism may crucially contribute to the mechanism with neurotoxicity on offspring generation after sevoflurane anesthesia in adult animals during pregnancy, and dietary supplement of S-Adenosylmethionine and modulating arginine/proline metabolism may be the potential therapeutic targets for protecting neurodevelopment from detrimental effects of prenatal exposure to inhalational anesthetics.