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Abstract Protein therapeutics are essential in treating various diseases, but their inherent biological instability and short circulatory half-lives in vivo pose challenges. Herein, a quantitative one-pot iterative living polymerization technique is reported towards precision control over the molecular structure and monomer sequence of protein-polymer conjugates, aiming to maximize physicochemical properties and biological functions of proteins. Using this quantitative one-pot iterative living polymerization technique, we successfully develop a series of sequence-controlled protein-multiblock polymer conjugates, enhancing their biostability, pharmacokinetics, cellular uptake, and in vivo biodistribution. All-atom molecular dynamics simulations are performed to disclose the definite sequence-function relationship of the bioconjugates, further demonstrating their sequence-encoded cellular uptake behavior and in vivo biodistribution in mice. Overall, this work provides a robust approach for creating precision protein-polymer conjugates with defined sequences and advanced functions as a promising candidate in disease treatment.

As an endogenous signaling molecule, carbon monoxide (CO) has emerged as an increasingly promising option regarding as gas therapy due to its positive pharmacological effects in various diseases. Owing to the gaseous nature and potential toxicity, it is particularly important to modulate the CO release dosages and targeted locations to elucidate the biological mechanisms of CO and facilitate its clinical applications. Based on these, diverse CO-releasing molecules (CORMs) have been developed for controlled release of CO in biological systems. However, practical applications of these CORMs are limited by several disadvantages including low stability, poor solubility, weak releasing controllability, random diffusion, and potential toxicity. In light of rapid developments and diverse advantages of nanomedicine, abundant nanomaterials releasing CO in controlled ways have been developed for therapeutic purposes across various diseases. Due to their nanoscale sizes, diversified compositions and modified surfaces, vast CO-releasing nanomaterials (CORNMs) have been constructed and exhibited controlled CO release in specific locations under various stimuli with better pharmacokinetics and pharmacodynamics. In this review, we present the recent progress in CORNMs according to their compositions. Following a concise introduction to CO therapy, CORMs and CORNMs, the representative research progress of CORNMs constructed from organic nanostructures, hybrid nanomaterials, inorganic nanomaterials, and nanocomposites is elaborated. The basic properties of these CORNMs, such as active components, CO releasing mechanisms, detection methods, and therapeutic applications, are discussed in detail and listed in a table. Finally, we explore and discuss the prospects and challenges associated with utilizing nanomaterials for biological CO release.

BackgroundAlzheimer’s disease (AD) is a degenerative disorder of the central nervous system characterized by notable pathological features such as neurofibrillary tangles and amyloid beta deposition. Additionally, the significant iron accumulation in the brain is another important pathological hallmark of AD. Exercise can play a positive role in ameliorating AD, but the mechanism is unclear. The purpose of the study is to explore the effect of regular aerobic exercise iron homeostasis and lipid antioxidant pathway regarding ferroptosis in the prefrontal cortex (PFC) of APPSwe/PSEN1dE9 (APP/PS1) mice.MethodsEighty 6-month-old C57BL/6 J and APP/PS1 mice were divided equally into 8-weeks aerobic exercise groups and sedentary groups. Subsequently, Y-maze, Morris water maze test, iron ion detection by probe, Western Blot, ELISA, RT-qPCR, HE, Nissle, Prussian Blue, IHC, IF, and FJ-C staining experiments were conducted to quantitatively assess the behavioral performance, iron levels, iron-metabolism-related proteins, lipid antioxidant-related proteins and morphology in each group of mice.ResultsIn APP/PS1 mice, the increase in heme input proteins and heme oxygenase lead to the elevated levels of free iron in the PFC. The decrease in ferritin content by ferritin autophagy fails to meet the storage needs for excess free iron within the nerve cells. Ultimately, the increase of free ferrous iron triggers the Fenton reaction, may lead to ferroptosis and resulting in cognitive impairment in APP/PS1 mice. However, 8-weeks aerobic exercise induce upregulation of the Xc−/GPx4 pathway, which can reverse the lipid peroxidation process, thereby inhibiting ferroptosis in APP/PS1 mice.Conclusion8 weeks aerobic exercise can improve learning and memory abilities in AD, upregulate GPx4/Xc− pathway in PFC to reduce ferroptosis induced by AD.

Synthetic chemistry has played a vital role in miscellaneous fields of human civilization over the past century. The synthetic stage yet remains time-consuming and labor-intensive. To overcome these limitations, automation has been introduced to transform synthetic chemistry, leading to the development of high-throughput methods for molecular discovery. Automated flow chemical synthesis (AFCS) has recently emerged as a promising candidate, offering improved efficiency, scalability, and sustainability over the well-known automated solid-phase peptide synthesis. To further advance AFCS, elements like artificial intelligence-based computer-aided structure design and synthesis planning, autonomously assembled compatible synthesis with enhanced automated process control, and autonomous optimization can be considered. This review focuses on recent advances in computer-aided automated flow chemical synthesis (CAAFCS) of polymers in living polymerization and iterative synthesis strategy. The current challenges and outlook are finally discussed for developing more powerful CAAFCS systems and expanding their applicability across numerous fields, potentially providing brand-new perspectives and guidelines for future developments in this field.

Cisplatin (CDDP) is widely used as one kind of chemotherapy drugs in cancer treatment. It functions by interacting with DNA, leading to the DNA damage and subsequent cellular apoptosis. However, the presence of intracellular PARP1 diminishes the anticancer efficacy of CDDP by repairing DNA strands. Olaparib (OLA), a PARP inhibitor, enhances the accumulation of DNA damage by inhibiting its repair. Therefore, the combination of these two drugs enhances the sensitivity of CDDP chemotherapy, leading to improved therapeutic outcomes. Nevertheless, both drugs suffer from poor water solubility and limited tumor targeting capabilities. To address this challenge, we proposed the self-assembly of two drugs, CDDP and OLA, through hydrogen bonding to form stable and uniform nanoparticles. Self-assembled nanoparticles efficiently target tumor cells and selectively release CDDP and OLA within the acidic tumor microenvironment, capitalizing on their respective mechanisms of action for improved anticancer therapy. In vitro studies demonstrated that the CDDP-OLA NPs are significantly more effective than CDDP/OLA mixture and CDDP at penetrating cancer cells and suppressing their growth. In vivo studies revealed that the nanoparticles specifically accumulated at the tumor site and enhanced the therapeutic efficacy without obvious adverse effects. This approach holds great potential for enhancing the drugs’ water solubility, tumor targeting, bioavailability, and synergistic anticancer effects while minimizing its toxic side effects.

A well-defined virus-like cage hybrid (VCH) with 24 covalent organic cages (COCs) attached to one metal organic cage (MOC) is presented here. The quantitative assembly of VCH was completed through coordination between soluble anisotropic COC bearing one bipyridine moiety and Pd(II) ions. The obtained VCH exhibited discrete, uniform and stable structures with good solubility and was well characterized by NMR, FT-IR, TEM, AFM, DLS, TGA, and so on. This designable cage hybrid promotes a new strategy to expand the structural and functional complexities of porous molecular cages.

The traditional freeway safety studies with “poststatic” thinking basically use cross-sectional data or panel data, which find it difficult to figure out real-time traffic crash risk factors. With the development of information collection technology, it is possible to obtain high-resolution traffic flow data currently, which provide a data basis for the dynamic traffic safety research towards freeways. This research aims at accurately identifying the real-time traffic crash precursors on freeways and addressing the shortcomings of conventional dynamic traffic safety research with the thinking of limited factor dimensions. In this research, dimensional data were applied as input model variables, the input dataset includes traffic crash data and the matched dynamic traffic flow data, and weather information and road characteristics were also considered to figure out the interaction effects between these dimensional factors. The XGBoost (eXtreme Gradient Boosting) was carried out to identify the dynamic crash-prone variables and the SHAP (SHapley Additive exPlanations) interpreter was introduced to interpret the XGBoost model, as well as the visualization of the influence of each eigenvalue on the traffic crash was realized. The results indicate that, in addition to traffic flow variables, road, weather, and temporal characteristics also have an impact on the traffic crash risk, and there is an interaction between each feature. The results of this research can provide the theoretical basis for freeway real-time traffic crash prediction and safety control.

Since cooling and heating loads are recognized as key characteristics for evaluating the energy efficiency of buildings, it appears indisputable that they must be predicted and analyzed for residential structures. Accordingly, the multi-layer perceptron neural network is applied for predicting the heating and cooling loads using the experimental dataset. The used dataset is obtained by monitoring the impact of the building's dimensions on energy consumption. To optimize the training process of the multi-layer perceptron neural network, several optimizers are employed. Besides, different statistical performance indicators are considered to see which selected optimizer outperforms the rest in terms of accuracy and authenticity. The obtained results emphasize the remarkable performance of adaptive chaotic grey wolf optimization, which can be used to train the multi-layer perceptron neural network and forecast the buildings’ energy consumption with the highest accuracy. According to the obtained results, the hybrid multi-layer perceptron neural network- adaptive chaotic grey wolf optimization method demonstrates the best performance. The optimum number of neurons in the hidden layer is obtained to be 15. Also, based on the statistical performance indicators, the selected method reveals an R 2 of 0.9123 and 0.9419 for cooling and heating loads, respectively.

Assisted reproductive technology has important clinical applications and commercial values in the horse industry. However, this approach is limited largely by the low efficiency of oocyte in vitro maturation (IVM), especially cytoplasmic maturation. To improve the efficiency of mare oocyte IVM, we evaluated the effects of co-culture with cumulus–oocyte complexes (COCs) and granulosa cells (GCs) from follicles with small (35 mm). Our results showed that oocyte nucleus maturation was not significantly improved by co-culturing with GCs. Interestingly, the cytoplasmic maturation of oocytes, defined by the distribution of cortical granules and mitochondria, as well as reactive oxygen species (ROS) levels, improved dramatically by co-culture with GCs, especially those derived from small follicles. Moreover, GCs promoted cumulus cell expansion by upregulating the expression of BMP15 in oocytes. To determine the mechanism underlying the effects of GCs, the transcriptomes of GCs from large and small follicles were compared. Expression levels of COL1A2, COL6A1, and COL6A2 were significantly higher in GCs from small follicles than in those from large follicles. These three genes were enriched in the extracellular matrix proteins-receptor interaction pathway and were involved in the regulation of collagens. Taken together, our results suggest that co-culture with GCs is beneficial to oocyte cytoplasmic maturation, and the increased expression of COL1A2, COL6A1, and COL6A2 improve the mare oocyte IVM system via the regulation of collagen.

Abstract Icing and frosting on transparent surfaces compromise visibility on various optical equipment and transparent infrastructures. It remains challenging to fabricate energy‐saving coatings for harvesting solar energy while maintaining high transparency. Here, transparent, photothermic, and icephobic composite surfaces composed of photothermal nanomaterials and polyelectrolytes via layer‐by‐layer assembly are designed and constructed. The positively‐charged polypyrrole nanoparticles and negatively‐charged poly(acrylic acid) are assembled as exemplary materials via electrostatic attractions. The optically transparent photothermal coatings are successfully fabricated and exhibited photothermal capabilities and light‐transmittance performance. Among the various coatings applied, the seven‐bilayer coating can increase the temperature by 35 °C under 1.9‐sun illumination, maintaining high transmittance (>60%) of visible light. With sunlight illumination at subzero temperatures (> −35 °C), the coatings show pronounced capabilities to inhibit freezing, melt accumulated frost, and decrease ice adhesion. Precisely, the icephobic surfaces remain free of frost at −35 °C as long as sunlight illumination is present; the accumulated frost melts rapidly within 300 s. The ice adhesion strength decreases to ≈0 kPa as the melted water acts as a lubricant. Furthermore, the negatively‐charged graphene oxide and positively‐charged poly(diallyldimethylammonium chloride) show their material diversity applicable in the coating fabrication.

Abstract Combinatorial therapy based on chemotherapeutic drugs and gene agents to achieve synergistic antitumor effects has emerged as a new direction for cancer treatment. However, simple and efficient co‐delivery of those two drug categories remains a key challenge in this hot area owing to their substantially different pharmacodynamics, impeding the translational potentials of combinatorial approaches. To address this issue, herein we propose a simple strategy to site‐specifically graft camptothecins (CPTs, a representative chemodrug) onto a DNA with dual functional segments, including an AS1411 aptamer sequence to target the cancer cell and a BCL‐2 antisense sequence to down‐regulate the anti‐apoptotic gene. The obtained DNA‐drug conjugate possesses precise chemical composition, controllable drug loading ratio, and responsive disulfide linkage, which can serve as a novel type of chemogene for combinatorial cancer therapy. In both in vitro and in vivo evaluations, our CPT‐bearing chemogene exhibit the targeted co‐delivery of chemo and gene agents to tumor site, efficient BCL‐2 gene knockdown, and strong induced apoptosis of cancer cells, together leading into an enhanced antitumor efficacy. With simple and precise structure as well as facile synthetic procedure, the new chemogene may turn into a promising drug formulation for combinatorial antitumor treatment.

Summary: Hydrogels have gained tremendous attention due to their versatility in soft electronics, actuators, biomedical sensors, etc. Due to the high water content, hydrogels are usually soft, weak, and freeze below 0°C, which brings severe limitations to applications such as soft robotics and flexible electronics in harsh environments. Most existing anti-freezing gels suffer from poor mechanical properties and urgently need further improvements. Here, we took inspirations from tendon and coniferous trees and provided an effective method to strengthen polyvinyl alcohol (PVA) hydrogel while making it freeze resistant. The salting-out effect was utilized to create a hierarchically structured polymer network, which induced superior mechanical properties (Young's modulus: 10.1 MPa, tensile strength: 13.5 MPa, and toughness: 127.9 MJ/m3). Meanwhile, the cononsolvency effect was employed to preserve the structure and suppress the freezing point to −60°C. Moreover, we have demonstrated the broad applicability of our material by fabricating PVA hydrogel-based hydraulic actuators and ionic conductors.

p53 is a common tumor suppressor, and its mutation drives tumorigenesis. What is more, p53 mutations have also been reported to be indicative of poor prognosis in lung cancer, but the detailed mechanism has not been elucidated. In this study, we found that DNA primase subunit 2 (PRIM2) had a high expression level and associated with poor prognosis in lung cancer. Furthermore, we found that PRIM2 expression was abnormally increased in lung cancer cells with p53 mutation or altered the p53/RB pathway based on database. We also verified that PRIM2 expression was elevated by mutation or deletion of p53 in lung cancer cell lines. Lastly, silence p53 increased the expression of RPIM2. Thus, these data suggest that PRIM2 is a cancer-promoting factor which is regulated by the p53/RB pathway. The p53 tumor-suppressor gene integrates numerous signals that control cell proliferation, cell cycle, and cell death; and the p53/RB pathway determines the cellular localization of transcription factor E2F, which regulates the expression of downstream targets. Next, we explored the role of PRIM2 in lung cancer and found that knockdown of PRIM2 induced cell cycle arrest, increased DNA damage, and increased cell senescence, leading to decreased lung cancer cell proliferation. Lastly, the positive correlation between PRIM2 and E2F/CDK also indicated that PRIM2 was involved in promoting cell cycle mediated by p53/RB pathway. These results confirmed that the expression of PRIM2 is regulated by the p53/RB pathway in lung cancer cells, promotes DNA replication and mismatch repair, and activates the cell cycle. Overall, we found that frequent p53 mutations increased PRIM2 expression, activated the cell cycle, and promoted lung cancer progression.

Abstract With the emergence of soft electronic devices, the requirements for conductive soft materials are unprecedentedly high. Among various soft materials, hydrogels are gaining tremendous attention for their superior softness, wetness, responsiveness, and biocompatibility. However, hydrogels inevitably lose elasticity and ionic conductivity at subzero temperature because of water freezing in the polymer matrices, severely limiting applications at low temperatures. Herein, we propose a rapid fabrication strategy to produce anti‐freezing conductive gels with poly(vinyl alcohol) on a large scale within minutes (vs hours/days in conventional methods) using a water/DMSO binary liquid system, which serves as gelation inducer via cononsolvency and anti‐freezing solvents simultaneously. The gel with 60 wt% DMSO shows the best anti‐freezing performance, remaining unfrozen at temperatures lower than −50°C, while also maintaining the highest mechanical properties with a tensile strength of 1.1 MPa, toughness of 10.9 MJ/m3, and elongation of 1500% outperforming the most previous reports. After incorporating H2SO4, the gels exhibit a high ionic conductivity of 5.25 S/m and maintain 1.65 S/m even at −50°C. Furthermore, an all‐in‐one supercapacitor is fabricated to demonstrate the potential of the anti‐freezing gel in soft device applications with good performance at subzero temperatures. A full recyclability of the material was also demonstrated.

Soil erodibility K factor is an important parameter for evaluating soil erosion vulnerability and is required for soil erosion prediction models. It is also necessary for soil and water conservation management. In this study, we investigated the spatial variability characteristics of soil erodibility K factor in a watershed (Changyan watershed with an area of 8.59 km2) of Enshi, southwest of Hubei, China, and evaluated its influencing factors. The soil K values were determined by the EPIC model using the soil survey data across the watershed. Spatial K value prediction was conducted by regression-kriging using geographic data. We also assessed the effects of soil type, land use, and topography on the K value variations. The results showed that soil erodibility K values varied between 0.039–0.052 t·hm2·h/(hm2·MJ·mm) in the watershed with a block-like structure of spatial distribution. The soil erodibility, soil texture, and organic matter content all showed positive spatial autocorrelation. The spatial variability of the K value was related to soil type, land use, and topography. The calcareous soil had the greatest K value on average, followed by the paddy soil, the yellow-brown soil (an alfisol), the purple soil (an inceptisol), and the fluvo-aquic soil (an entisol). The soil K factor showed a negative correlation with the sand content but was positively related to soil silt and clay contents. Forest soils had a greater ability to resist to erosion compared to the cultivated soils. The soil K values increased with increasing slope and showed a decreasing trend with increasing altitude.

Abstract Small molecule nanodrugs consisting of pure drugs, drug‐drug dimers, drug‐drug conjugates, or drug derivatives could realize drug delivery by themselves without the aid of carriers, which have received abundant attention in recent decades. Avoiding the use of additional carriers, the yielded small molecule nanodrugs hold the following advantages: (a) high drug loading capacities (some of them could even reach up to 100%); (b) precise and tunable drug loading ration; and (c) no carrier‐induced long‐term toxicity. The past decade has witnessed rapid growth and advancements in this field. In this review, we will briefly introduce both in vitro “barriers” and in vivo barriers for drug delivery, and then summarize the most recent development of small molecule nanodrugs from the point of view how to engineer small molecule nanodrugs to overcome these barriers.

Calcific aortic valve disease (CAVD), a common heart valve disease, is increasingly prevalent worldwide and causes high morbidity and mortality. Here, we aimed to investigate a possible role for miR-34c in the development of osteogenic differentiation during CAVD and to find out the underlying mechanisms. Valvular interstitial cells (VICs) were isolated from the clinical aortic valve tissue samples of CAVD patients and patients with acute aortic dissection and collected. Then, RT-qPCR was performed to determine miR-34c expression and western blot analysis was applied to confirm the relevant protein expression in these VICs. Dual luciferase reporter gene assay was applied to confirm the relation between miR-34c and STC1. Alkaline phosphatase (ALP) staining and alizarin red staining was performed to further confirm the degree of calcification in these samples. MiR-34c was lowly expressed and STC1 was highly expressed in the CAVD tissues. Furthermore, STC1 was the target of miR-34c and was negatively regulated by miR-34c. Overexpression of miR-34c in VICs was concomitant with suppression of both STC1 expression and phosphorylation level of c-Jun N-terminal kinase (JNK). In addition, significant decrease of bone morphogenetic protein-2 (BMP2) and osteocalcin, as well as the decrease of calcification degree were also observed in VICs with miR-34c overexpressed. Taken together, miR-34c could inhibit osteogenic differentiation and calcification of VICs by suppressing the STC1/JNK signaling pathway in CAVD, making miR-34c a novel therapeutic target for the treatment of CAVD.

Vibrios, which include more than 120 valid species, are an abundant and diverse group of bacteria in marine and estuarine environments. Some of these bacteria have been recognized as pathogens of both marine animals and humans, and therefore, their virulence mechanisms have attracted increasing attention. The type III secretion system (T3SS) is an important virulence determinant in many gram-negative bacteria, in which this system directly translocates variable effectors into the host cytosol for the manipulation of the cellular responses. In this study, the distribution of the T3SS gene cluster was first examined in 110 Vibrio strains of 26 different species, including 98 strains isolated from coastal areas in China. Several T3SS1 genes, but not T3SS2 genes (T3SS2α and T3SS2β), were universally detected in all the strains of four species, Vibrio parahaemolyticus, Vibrio alginolyticus, Vibrio harveyi, and Vibrio campbellii. The effector coding regions within the T3SS1 gene clusters from the T3SS1-positive strains were further analyzed, revealing that variations in the effectors of Vibrio T3SS1 were observed among the four Vibrio species, even between different strains in V. harveyi, according to their genetic organization. Importantly, Afp17, a potential novel effector that may exert a similar function as the known effector VopS in T3SS1-induced cell death, based on cytotoxicity assay results, was found in the effector coding region of the T3SS1 in some V. harveyi and V. campbellii strains. Finally, it was revealed that differences in T3SS1-mediated cytotoxicity were dependent not only on the variations in the effectors of Vibrio T3SS1 but also on the initial adhesion ability to host cells, which is another prerequisite condition. Altogether, our results contribute to the clarification of the diversity of T3SS1 effectors and a better understanding of the differences in cytotoxicity among Vibrio species.

The genus Vibrio is a genetically and metabolically versatile group of heterotrophic bacteria that are important contributors to carbon cycling within marine and estuarine ecosystems. HN897, a Vibrio strain isolated from the coastal seawater of South China, was shown to be agarolytic and capable of catabolizing D-galactose. Herein, we used Illumina and PacBio sequencing to assemble the whole genome sequence for the strain HN897, which was comprised of two circular chromosomes (Vas1 and Vas2). Genome-wide phylogenetic analysis with 140 other Vibrio sequences firmly placed the strain HN897 into the Marisflavi clade, with Vibrio astriarenae strain C7 being the closest relative. Of all types of carbohydrate-active enzyme classes, glycoside hydrolases (GH) were the most common in the HN897 genome. These included eight GHs identified as putative β-agarases belonging to GH16 and GH50 families in equal proportions. Synteny analysis showed that GH16 and GH50 genes were tandemly arrayed on two different chromosomes consistent with gene duplication. Gene knockout and complementation studies and phenotypic assays confirmed that Vas1_1339, a GH16_16 subfamily gene, exhibits an agarolytic phenotype of the strain. Collectively, these findings explained the agar-decomposing of strain HN897, but also provided valuable resources to gain more detailed insights into the evolution and physiological capability of the strain HN897, which was a presumptive member of the species V. astriarenae.

Photodynamic therapy has attracted interest in treating cancer but it is limited in hypoxic tumors due to a lack of oxygen. Here, the authors describe a nano-composite capable of generating oxygen under near-infrared light for improved photodynamic and chemotherapy for treating cancer.

The effects of soy extract fermented by Lactobacillus plantarum WW (L. plantarum WW) on high fat diet (HFD)-induced hyperlipidemia and liver injury were examined. Sprague-Dawley rats were randomly divided into normal chow (C), HFD and HFD + L. plantarum WW-fermented soy extract (HFD + FSE). We found that L. plantarum WW-FSE treatment significantly restored changes to body weight and pathological indices caused by fatty liver disease. RNA-seq analysis showed that treatment with L. plantarum WW-FSE altered expression of genes involved in lipid metabolism, and in oxidation-reduction processes. This study supported that the peroxisome proliferator-activated receptor (PPAR) signaling pathway may be involved in lipid metabolism, and suggested that dietary L. plantarum WW-FSE ameliorates HFD-induced lipid metabolism disturbance in rat liver associated with PPAR signaling pathway. These observations shed new light on possible treatment of hyperlipidemia.

Primary hyperoxaluria type 1 (PH1) is a rare metabolic disorder characterized by a defect in the liver-specific peroxisomal enzyme alanine-glyoxylate and serine-pyruvate aminotransferase (AGT). This disorder results in hyperoxaluria, recurrent urolithiasis, and nephrocalcinosis. Three forms of PH1 have been reported. Data on the infantile form of PH1 are currently limited in literature. Despite the fact that China is the most populated country in the world, only a few AGXT mutations have been reported in several Chinese PH1 patients. In the present study, we investigated a Chinese family in which two siblings are affected by the infantile form of PH1. Sanger sequencing was carried out on the proband, but the results were misleading. Two novel missense mutations (c.517T > C/p.Cys173Arg and c.667A > C/p.Ser223Arg) of the AGXT gene were successfully detected through whole-exome sequencing. These two mutations occurred in the highly conserved residues of the AGT. Four software programs predicted both mutations as the cause of the disease. A postmortem examination was performed and revealed the occurrence of global nephrocalcinosis on both kidneys. The crystals were collected and analyzed as calcium oxalate monohydrate. This study extends the knowledge on the clinical phenotype–genotype correlation of the AGXT mutation. That is, (i) two novel missense mutations were identified for the infantile form of PH1 and (ii) the same AGXT genotype caused the same infantile form of PH1 within the family.

It is undeniable that developing a simple fabrication procedure for transition-metal phosphides can significantly enhance their potential for commercial use in energy storage and conversion applications. This work focuses on the fabrication of cobalt-nickel phosphide nanoneedle arrays as supercapacitors using nickel foam (NF) as a substrate and a source of Ni ions. By controlling the phosphating process of the Co precursor/NF, it was strikingly found that different surface morphologies emerged in phosphorized NiCo-based electrodes. Taking advantage of nanoneedle/nanorod-type structures and transition phosphides, the CP2 electrode exhibits an exceptional specific capacitance of 2444 F/g (1222 C/g) at 1 A/g. It demonstrates an outstanding rate performance with a retention rate of 43.17% even at 25 A/g. The electrochemistry that occurs during storage at the positive poles was further investigated based on reaction kinetics, revealing intriguing electrochemical storage behaviors. Coupled with a power density of 872.08 W/kg, the CP2//PC supercapacitor demonstrates a significant energy density of 32.53 Wh/kg and displays favorable capacitance retention rate characteristics (58.7% for the initial 5000 cycles and 50.8% for the subsequent 5000 cycles). The enduring cycling performance of the CP2 electrode featuring a superior nanoneedle/nanorod array structure may be attributed to the inherent self-supporting design and enhanced phosphorization process. The design of high-performance supercapacitors is realized by reducing the dead volume and improving conductivity. [ABSTRACT FROM AUTHOR]

An efficient, concise 5-step synthetic approach to γ-aminobutyric acid (GABA) derivatives bearing bridged bicyclo[2.2.2]octane and bicyclo[2.2.1]heptane rings was developed, which consists of Diels-Alder cycloaddition to construct the bridged bicyclic rings with a nitrile functionality, hydrogenation, LDA-mediated SN2 alkylation to introduce acetate moiety at the α-position of nitrile, reduction of the nitrile functionality to amino group followed by intramolecular formation of lactam and finally acidic hydrolysis of lactam to give the desired GABA derivatives (1 and 19 as HBr salts). The reaction conditions of Diels-Alder cycloaddition and LDA-mediated SN2 alkylation were intensively optimized to improve the yields. The stereochemistry of the SN2 reaction involved in the bicyclo[2.2.1]heptane ring system was unambiguously elucidated by single-crystal X-ray diffraction. This synthetic approach possesses advantages of less reaction steps, high overall yields and avoidance of toxic reagents, and may find wide applications in the synthesis of other GABA derivatives with similar bicyclic or polycyclic rings. [ABSTRACT FROM AUTHOR]