Hyaluronic acid-modified mesoporous silica nanoprobes for target identification of atherosclerosis.

Rupture of vulnerable plaque and secondary thrombosis caused by atherosclerosis are one of the main causes of acute cardiovascular and cerebrovascular events, and it is urgent to develop an in-situ, noninvasive, sensitive and targeted detection method at molecular level. We chose CD44, a specific receptor highly expressed on the surface of macrophages, as the target of the molecular probe, and modified the CD44 ligand HA onto the surface of Gd2O3@MSN, constructing the MRI imaging nanoprobe HA-Gd2O3@MSN for targeted recognition of atherosclerosis. The fundamental properties of HA-Gd2O3@MSN were initially investigated. The CCK-8, hemolysis, hematoxylin-eosin staining tests and blood biochemical assays confirmed that HA-Gd2O3@MSN possessed excellent biocompatibility. Laser confocal microscopy, cellular magnetic resonance imaging, flow cytometry and immunohistochemistry were used to verify that the nanoprobes had good targeting properties. The in vivo targeting performance of the nanoprobes was further validated by employing a rabbit atherosclerosis animal model. In summary, the synthesized HA-Gd2O3@MSN nanoprobes have excellent biocompatibility properties as well as good targeting properties. It could provide a new technical tool for early identification of atherosclerosis.

Wheat Seed Detection and Counting Method Based on Improved YOLOv8 Model.

Wheat seed detection has important applications in calculating thousand-grain weight and crop breeding. In order to solve the problems of seed accumulation, adhesion, and occlusion that can lead to low counting accuracy, while ensuring fast detection speed with high accuracy, a wheat seed counting method is proposed to provide technical support for the development of the embedded platform of the seed counter. This study proposes a lightweight real-time wheat seed detection model, YOLOv8-HD, based on YOLOv8. Firstly, we introduce the concept of shared convolutional layers to improve the YOLOv8 detection head, reducing the number of parameters and achieving a lightweight design to improve runtime speed. Secondly, we incorporate the Vision Transformer with a Deformable Attention mechanism into the C2f module of the backbone network to enhance the network's feature extraction capability and improve detection accuracy. The results show that in the stacked scenes with impurities (severe seed adhesion), the YOLOv8-HD model achieves an average detection accuracy (mAP) of 77.6%, which is 9.1% higher than YOLOv8. In all scenes, the YOLOv8-HD model achieves an average detection accuracy (mAP) of 99.3%, which is 16.8% higher than YOLOv8. The memory size of the YOLOv8-HD model is 6.35 MB, approximately 4/5 of YOLOv8. The GFLOPs of YOLOv8-HD decrease by 16%. The inference time of YOLOv8-HD is 2.86 ms (on GPU), which is lower than YOLOv8. Finally, we conducted numerous experiments and the results showed that YOLOv8-HD outperforms other mainstream networks in terms of mAP, speed, and model size. Therefore, our YOLOv8-HD can efficiently detect wheat seeds in various scenarios, providing technical support for the development of seed counting instruments.

Amphiphilic Polymer Electrolyte Blocking Lattice Oxygen Evolution from High-Voltage Nickel-rich Cathodes for Ultra-Thermal Stabile Batteries.

Ni-rich cathodes have been intensively adopted in Li-ion batteries to pursuit high energy density, which still suffering irreversible degradation at high voltage. Some unstable lattice O2- species in Ni-rich cathodes would be oxidized to singlet oxygen 1O2 and released at high volt, which lead to irreversible phase transfer from the layered rhombohedral (R) phase to a spinel-like (S) phase. To overcome the issue, the amphiphilic copolymers (UMA-Fx) electrolyte were prepared by linking hydrophobic C-F side chains with hydrophilic subunits, which could self-assemble on Ni-rich cathode surface and convert to stable cathode-electrolyte interphase layer. Thereafter, the oxygen releasing of polymer coated cathode was obviously depressed and substituted by the Co oxidation (Co3+→Co4+) at high volt (>4.2 V), which could suppressed irreversible phase transfer and improve cycling stability. Moreover, the amphiphilic polymer electrolyte was also stable with Li anode and had high ion conductivity. Therefore, the NCM811//UMA-F6//Li pouch cell exhibited outstanding energy density (362.97 Wh/kg) and durability (cycled 200 times at 4.7 V), which could be stalely cycled even at 120°C without short circuits or explosions.

Functionalized europium-doped hollow mesoporous silica nanospheres as a cell imaging and drug delivery agents.

In an effort to enhance the antitumor efficacy of breast cancer treatment, the chemotherapeutic agent Paclitaxel (PTX) was encapsulated within hyaluronic acid (HA) modified hollow mesoporous silica (HMSNs). In vitro drug release assays showed that the resulting formulation, Eu-HMSNs-HA-PTX, exhibited enzyme-responsive drug release. In addition, cell cytotoxicity and hemolysis assays demonstrated the favorable biocompatibility of both Eu-HMSNs and Eu-HMSNs-HA. Notably, compared to Eu-HMSNs alone, Eu-HMSNs-HA showed enhanced accumulation within CD44-expressing cancer cells (MDA-MB-231). As anticipated, apoptosis experiments indicated that Eu-HMSNs-HA-PTX displayed significantly greater cytotoxicity toward MDA-MB-231 cells than non-targeted Eu-HMSNs-PTX and free PTX. In conclusion, Eu-HMSNs-HA-PTX demonstrated excellent anticancer effects and holds promise as a potent candidate for the efficient therapy of breast cancer.

A heterozygous mutation in ITGB4 causing a mild phenotype of junctional epidermolysis bullosa.

Mutations in ITGB4 are known to cause autosomal recessive junctional epidermolysis bullosa (JEB), which is manifested by severe blistering and granulation tissue, usually complicating pyloric atresia and even leading to death. ITGB4-associated autosomal dominant epidermolysis bullosa has rarely been documented. Herein, we identified a heterozygous pathogenic variant (c.433G>T; p.Asp145Tyr) in ITGB4 causing a mild phenotype of JEB in a Chinese family.

Enterokinase deficiency with novel TMPRSS15 gene mutation masquerading as acrodermatitis enteropathica.

Enterokinase deficiency (EKD) is a rare autosomal recessive inherited disorder caused by loss-of-function mutations of the transmembrane protease serine 15 (TMPRSS15) gene. To date, only 12 cases of EKD have been described in the literature and skin involvement has seldom been described. We identified a novel homozygous nonsense mutation in the TMPRSS15 gene (c.1216C>T, p.R406*) in a female infant, who manifested with acrodermatitis enteropathica (AE)-like lesions that were dramatically relieved within 11 days after initiation of a protein-rich hydrolyzed formula. Our case shows that AE-like rashes can be a manifestation of EKD and expands the spectrum of causative mutations in the TMPRSS15 gene.

Engineered Graphene Quantum Dots as a Magnetic Resonance Signal Amplifier for Biomedical Imaging.

The application of magnetic resonance imaging (MRI) nano-contrast agents (nano-CAs) has increasingly attracted scholarly interest owing to their size, surface chemistry, and stability. Herein, a novel T1 nano-CA (Gd(DTPA)-GQDs) was successfully prepared through the functionalization of graphene quantum dots with poly(ethylene glycol) bis(amine) and their subsequent incorporation into Gd-DTPA. Remarkably, the resultant as-prepared nano-CA displayed an exceptionally high longitudinal proton relaxivity (r1) of 10.90 mM-1 s-1 (R2 = 0.998), which was significantly higher than that of commercial Gd-DTPA (4.18 mM-1 s-1, R2 = 0.996). The cytotoxicity studies indicated that the Gd(DTPA)-GQDs were not cytotoxic by themselves. The results of the hemolysis assay and the in vivo safety evaluation demonstrate the outstanding biocompatibility of Gd(DTPA)-GQDs. The in vivo MRI study provides evidence that Gd(DTPA)-GQDs exhibit exceptional performance as T1-CAs. This research constitutes a viable approach for the development of multiple potential nano-CAs with high-performance MR imaging capabilities.

Combination of Mn-Mo Oxide Nanoparticles on Carbon Nanotubes through Nitrogen Doping to Catalyze Oxygen Reduction.

An efficient and low-cost oxygen catalyst for the oxygen reduction reaction (ORR) was developed by in situ growth of Mn-Mo oxide nanoparticles on nitrogen-doped carbon nanotubes (NCNTs). Doped nitrogen effectively increases the electron conductivity of the MnMoO4@NCNT complex and the binding energy between the Mn-Mo oxide nanoparticles and carbon nanotubes (CNTs), leading to fast charge transfer and more catalytically active sites. Combining Mn and Mo with NCNTs improves the catalytic activity and promotes both electron and mass transfers, greatly enhancing the catalytic ability for ORR. As a result, MnMoO4@NCNT exhibited a comparable half-wave potential to commercial Pt/C and superior durability, demonstrating great potential for application in renewable energy conversion systems.

cRGD-Conjugated GdIO Nanoclusters for the Theranostics of Pancreatic Cancer through the Combination of T1-T2 Dual-Modal MRI and DTX Delivery.

Clinically, magnetic resonance imaging (MRI) often uses contrast agents (CAs) to improve image contrast, but single-signal MRI CAs are often susceptible to calcification, hemorrhage, and magnetic sensitivity. Herein, iron acetylacetone and gadolinium acetylacetone were used as raw materials to synthesize a T1-T2 dual-mode imaging gadolinium-doped iron oxide (GdIO) nanocluster. Moreover, to endow the nanoclusters with targeting properties and achieve antitumor effects, the cyclic Arg-Gly-Asp (cRGD) peptide and docetaxel (DTX) were attached to the nanocluster surface, and the efficacy of the decorated nanoclusters against pancreatic cancer was evaluated. The final synthesized material cRGD-GdIO-DTX actively targeted αvß3 on the surface of Panc-1 pancreatic cancer cells. Compared with conventional passive targeting, the enrichment of cRGD-GdIO-DTX in tumor tissues improved, and the diagnostic accuracy was significantly enhanced. Moreover, the acidic tumor microenvironment triggered the release of DTX from cRGD-GdIO-DTX, thus achieving tumor treatment. The inhibition of the proliferation of SW1990 and Panc-1 pancreatic cancer cells by cRGD-GdIO-DTX was much stronger than that by the untargeted GdIO-DTX and free DTX in vitro. In addition, in a human pancreatic cancer xenograft model, cRGD-GdIO-DTX considerably slowed tumor development and demonstrated excellent magnetic resonance enhancement. Our results suggest that cRGD-GdIO-DTX has potential applications for the precise diagnosis and efficient treatment of pancreatic cancer.

Hyperpigmentation in a Chinese family with autosomal dominant Cole disease.

Cole disease (OMIM 615522), caused by mutations in ENPP1, is a rare autosomal dominant or recessive genodermatosis characterized by guttate hypopigmentation and punctate palmoplantar keratoderma. To date, a few cases with autosomal recessive inheritance had been reported with hyperpigmentation. The aim of this case report was to investigate the molecular basis of individuals with hyperpigmentation, hypopigmentation and punctate keratoderma in a Chinese family. A Chinese pedigree of suspected Cole disease with hyperpigmentation was subjected to mutation detection in the ENPP1 gene. All exons of the ENPP1 gene and adjacent exon-intron border sequences were amplified using polymerase chain reaction and directly sequenced. Three-dimensional (3D) models of the wild-type and mutated ENPP1 proteins were predicted by PyMOL viewer. Both of the proband and his affected father carried a heterozygous missense mutation p.C176R in ENPP1. In silico modelling of the ENPP1 wild-type and ENPP1 with the p.C176R mutation showed the residue Arg-176 disturbed the fold of the loop conformation. Based on clinical and genetic findings, a diagnosis of Cole disease was made. We identified a heterozygous mutation, p.C176R, in the ENPP1 gene in a Chinese family with Cole disease. This study clearly showed that hyperpigmentation could also occur in Cole disease in cases with autosomal dominant inheritance. Our data expand the phenotypic spectrum of ENPP1 mutations underlying Cole disease.

Secondary acrodermatitis enteropathica-like skin findings in a case of methylmalonic acidemia.

Methylmalonic acidemia (MMA) is an autosomal recessive genetic disorder caused by decreased activity of methylmalonyl-CoA mutase or metabolic disturbance of its coenzyme cobalamin, cutaneous manifestations are rare clinical signs in this disease. Herein, we describe a Chinese boy with MMA fed with a formula lacking branched-chain amino acids presenting with erythroderma and acrodermatitis enteropathica-like rash, a homozygous nonsense mutation c.742C>T (p.Gln248*) was identified in the MMAA gene. The pedigree exhibited a non-Mendelian inheritance pattern which was attributed to maternal uniparental disomy on chromosome 4q26-q34.1 of the proband, confirmed by chromosomal microarray analysis. Our case highlights the association between skin changes and nutritional deficiency due to therapeutic amino acid restrictions in MMA.

pH-Responsive Drug Delivery and Imaging Study of Hybrid Mesoporous Silica Nanoparticles.

A system of pH-responsive and imaging nanocarriers was developed using mesoporous silica nanoparticles (MSNs), in which gadolinium (Gd) was doped through in situ doping (Gd2O3@MSN). Sodium alginate (SA) was attached to the surfaces of the amino groups of MSNs (NH2-Gd2O3@MSN) through the electrostatic adsorption between the amino groups and the carboxyl groups with the formation of hybrid SA-Gd2O3@MSN nanoparticles (NPs). The SA-coated NPs were spherical or near-spherical in shape with an average size of nearly 83.2 ± 8.7 nm. The in vitro drug release experiments of a model rhodamine B (RhB) cargo were performed at different pH values. The result confirmed the pH-responsiveness of the nanocarriers. The results of the cytotoxicity studies indicated that the SA-Gd2O3@MSN NPs were not cytotoxic by themselves. The results of the in vivo safety evaluation and the hemolysis assay confirmed that the system is highly biocompatible. It is noteworthy that the T1 contrast of the system was significantly enhanced by the Gd, as indicated by the result of the MR imaging. This study confirms that the synthesized hybrid nanosystem is promising for pH-responsive drug delivery and MR imaging for cancer diagnosis and treatment.

Sulfone-Decorated Conjugated Organic Polymers Activate Oxygen for Photocatalytic Methane Conversion.

Oxidizing CH4 into liquid products with O2 under mild conditions still mainly relies on metal catalysis. We prepared a series of sulfone-modified conjugated organic polymers and found that the catalyst with proper SVI content (0.10) could drive O2 →H2 O2 →⋅OH to oxidize CH4 into CH3 OH and HCOOH directly and efficiently at room temperature under light irradiation. Experimental results showed that after 4 h reaction, decomposition rate and residual amounts of H2 O2 were 81.21 % and 4.83 mmol gcat -1 respectively, and CH4 conversion rate was 22.81 %. Mechanism studies revealed that illumination could induce the homolytic dissociation of S=O bonds on catalyst to produce oxygen and sulfur radicals, where the ⋅O could adsorb and activate CH4 , and the ⋅S could supply electrons for 1 O2 to generate H2 O2 and then for decomposing the H2 O2 into ⋅OH timely to oxidize CH4 . This research provided a novel organic catalysis approach for oxygen activation and utilization.

Fe/Fe3 C Boosts H2 O2 Utilization for Methane Conversion Overwhelming O2 Generation.

H2 O2 as a well-known efficient oxidant is widely used in the chemical industry mainly because of its homolytic cleavage into . OH (stronger oxidant), but this reaction always competes with O2 generation resulting in H2 O2 waste. Here, we fabricate heterogeneous Fenton-type Fe-based catalysts containing Fe-Nx sites and Fe/Fe3 C nanoparticles as a model to study this competition. Fe-Nx in the low spin state provides the active site for . OH generation. Fe/Fe3 C, in particular Fe3 C, promotes Fe-Nx sites for the homolytic cleavages of H2 O2 into . OH, but Fe/Fe3 C nanoparticles (Fe0 as the main component) with more electrons are prone to the undesired O2 generation. With a catalyst benefiting from finely tuned active sites, 18 % conversion rate for the selective oxidation of methane was achieved with about 96 % selectivity for liquid oxygenates (formic acid selectivity over 90 %). Importantly, O2 generation was suppressed 68 %. This work provides guidance for the efficient utilization of H2 O2 in the chemical industry.

Controllable Substitution of S Radicals on Triazine Covalent Framework to Expedite Degradation of Polysulfides.

Lithium-sulfur (Li-S) batteries are facing a significant barrier due to the diffusion of intermediate redox species. Although some S doped covalent framework cathodes have been reported with outstanding reversibility, the low content of sulfur (less than 30%) limits the practical applications. To overcome the issue, the sulfur and nitrogen co-doped covalent compounds (S-NC) as a host-type cathode have been developed through the radical transfer process during thermal cracking amino groups on the precursor, and then plentiful positively charged sulfur radicals can be controllably introduced. The experimental characterization and DFT theoretical calculation certificate that the sulfur radicals in S-NC/S can expedite redox reactions of intermediate polysulfides to impede their dissolution. Moreover, the energy barriers during ions transfer also obviously decreased after introducing S radicals, which lead to improved rate performance.

A novel homozygous mutation p.E88K in maternal SLC30A2 gene as a cause of transient neonatal zinc deficiency.

The SLC30A2 gene encodes zinc transporter ZnT2, which is indispensable for the transport of zinc into the breast milk in the mammary gland. Transient neonatal zinc deficiency (TNZD) is caused by a mutation in the maternal SLC30A2 gene and has a clinical presentation similar to that of acrodermatitis enteropathica (AE). We described the case of a Chinese infant who presented with AE-like lesions 10 days after birth. Sanger sequencing of the AE-causing gene SLC39A4 revealed no mutations in genomic DNA from the infant, excluding the possibility of AE. Detection of the mother's breast milk showed a significantly lower zinc level. Thus, SLC30A2 sequencing was performed on her genomic DNA and a previously unreported homozygous c.262G > A (p.E88K) mutation was disclosed. Functional analysis suggested the novel mutation could lead to a strong disruption of zinc secretion, which indicated a complete loss of function in the ZnT2 protein. We finally diagnosed the infant with TNZD. To the best of our knowledge, this is the first case of TNZD caused by a homozygous mutation in the maternal SLC30A2 gene. Compared to the heterozygous condition, a homozygous mutation seems to result in a more significant decrease in zinc secretion and a more rapid onset of TNZD.

Amorphous Iron(III)-Borate Nanolattices as Multifunctional Electrodes for Self-Driven Overall Water Splitting and Rechargeable Zinc-Air Battery.

Highly stable and low-cost electrocatalysts with multi-electrocatalytic activities are in high demand for developing advanced energy conversion devices. Herein, a unique trifunctional amorphous iron-borate electrode is developed, which is capable of boosting hydrogen evolution, oxygen evolution, and oxygen reduction reactions simultaneously. The amorphous iron borate can self-assemble into well-defined nanolattices on electrode surface through a facile hydrothermal process, which possess more active sites and charge transfer pathways. As a result, the asymmetry overall water-splitting cell that adopts the amorphous electrodes as anode and cathode can be driven at 1.56 V with the current density of 10 mA cm-2 , which is lowest in state-of-the-art catalysts. Moreover, the water-splitting devices can be powered by a two-series-connected amorphous electrode-based zinc-air battery with high stability and Faradic efficiency (96.3%). The result can offer a potential and promising alternative way to develop metal-borate electrode for multifunctional applications.

Unlocking the mystery of persistent skin ulcers in a young man and successful treatment with a simple regimen.

Despite the high prevalence of pulmonary tuberculosis worldwide, extrapulmonary tuberculosis especially cutaneous and osteoarticular tuberculosis occurs rarely, both of which are often difficult to be recognized since their symptoms mimic those of many other cutaneous and osteoarticular diseases. Here, we present a rare case of cutaneous tuberculosis potentially accompanied by osteroarticular tuberculosis in a 36-year-old Chinese man who presented with multiple persistent skin ulcers for one year and were nonresponsive to multiple therapeutic approaches. A single anti-tuberculous regimen with rifampicin resulted in healing of all skin lesions and excellent recovery of the general condition.

[Genetic Polymorphism of IL36RN in Han Patients with Generalized Pustular Psoriasis Alone in Sichuan Region].

OBJECTIVE: To detect interleukin-36-receptor antagonist gene (IL36RN) in Han patients with generalized pustular psoriasis (GPP) alone in Sichuan region for the purpose of clarification of GPP pathogenesis. METHODS: Genomic DNA of GPP patients, psoriasis vulgaris (PV) patients and normal controls was extracted and subjected to PCR for the amplification of entire encoding and splice sites of IL36RN gene followed by bidirectional sequencing. Differences in frequencies of IL36RN variants between three groups were analyzed. The variant frequency between pediatric-onset GPP (PGPP) and adult-onset GPP (AGPP) was also compared. RESULTS: Three IL36RN variants (c.115+6T>C, c.140A>G, c.227C>T) were found in Han GPP patients from Sichuan. Among them, c.115+6T>C had the highest frequency. Compared with PV patients and normal controls, all the variants frequency had statistical significance (P<0.05). There was no significant difference of variants frequency of IL36RN between PGPP and AGPP group (P>0.05). CONCLUSION: IL36RN may be the most common disease-causing gene in the patients with GPP alone in Han population from Sichuan region.

Cu-N dopants boost electron transfer and photooxidation reactions of carbon dots.

The broadband light-absorption ability of carbon dots (CDs) has inspired their application in photocatalysis, however this has been impeded by poor electron transfer inside the CDs. Herein, we report the preparation of Cu-N-doped CDs (Cu-CDs) and investigate both the doping-promoted electron transfer and the performance of the CDs in photooxidation reactions. The Cu-N doping was achieved through a one-step pyrolytic synthesis of CDs with Na2 [Cu(EDTA)] as precursor. As confirmed by ESR, FTIR, and X-ray photoelectron spectroscopies, the Cu species chelates with the carbon matrix through Cu-N complexes. As a result of the Cu-N doping, the electron-accepting and -donating abilities were enhanced 2.5 and 1.5 times, and the electric conductivity was also increased to 171.8 µs cm(-1) . As a result of these enhanced properties, the photocatalytic efficiency of CDs in the photooxidation reaction of 1,4-dihydro-2,6-dimethylpyridine-3,5-dicarboxylate is improved 3.5-fold after CD doping.