Ultrasensitive Ratiometric Fluorescent Nanothermometer with Reverse Signal Changes for Intracellular Temperature Mapping.

Sensing temperature at the subcellular level is pivotal for gaining essential thermal insights into diverse biological processes. However, achieving sensitive and accurate sensing of the intracellular temperature remains a challenge. Herein, we develop a ratiometric organic fluorescent nanothermometer with reverse signal changes for the ultrasensitive mapping of intracellular temperature. The nanothermometer is fabricated from a binary mixture of saturated fatty acids with a noneutectic composition, a red-emissive aggregation-caused quenching luminogen, and a green-emissive aggregation-induced emission luminogen using a modified nanoprecipitation method. Different from the eutectic mixture with a single phase-transition point, the noneutectic mixture possesses two solid-liquid phase transitions, which not only allows for reversible regulation of the aggregation states of the encapsulated luminogens but also effectively broadens the temperature sensing range (25-48 °C) across the physiological temperature range. Remarkably, the nanothermometer exhibits reverse and sensitive signal changes, demonstrating maximum relative thermal sensitivities of up to 63.66% °C-1 in aqueous systems and 44.01% °C-1 in the intracellular environment, respectively. Taking advantage of these outstanding thermometric performances, the nanothermometer is further employed to intracellularly monitor minute temperature variations upon chemical stimulation. This study provides a powerful tool for the exploration of dynamic cellular thermal activities, holding great promise in unveiling intricate physiological processes.

A universal strategy to enhance photothermal conversion efficiency by regulating the molecular aggregation states for safe photothermal therapy of bacterial infections.

Photothermal therapy (PTT) has emerged as a promising approach for treating bacterial infections. However, achieving a high photothermal conversion efficiency (PCE) of photothermal agents (PTAs) remains a challenge. Such a problem is usually compensated by the use of a high-intensity laser, which inevitably causes tissue damage. Here, we present a universal strategy to enhance PCE by regulating the molecular aggregation states of PTAs within thermoresponsive nanogels. We demonstrate the effectiveness of this approach using aggregation-induced emission (AIE) and aggregation-caused quenching (ACQ) PTAs, showing significant enhancements in PCE without the need for intricate molecular modifications. Notably, the highest PCEs reach up to 80.9% and 64.4% for AIE-NG and ACQ-NG, respectively, which are nearly 2-fold of their self-aggregate counterparts. Moreover, we elucidate the mechanism underlying PCE enhancement, highlighting the role of strong intermolecular π-π interactions facilitated by nanogel-induced volume contraction. Furthermore, we validate the safety and efficacy of this strategy in in vitro and in vivo models of bacterial infections at safe laser power densities, demonstrating its potential for clinical translation. Our findings offer a straightforward, universal, and versatile method to improve PTT outcomes while minimizing cytotoxicity, paving the way for enhanced treatment of bacterial infections with safe PTT protocols.

Hyperbaric Oxygen Therapy Inhibits Neuronal Ferroptosis After Spinal Cord Injury in Mice.

STUDY DESIGN: Basic science study investigating the potential molecular mechanisms of hyperbaric oxygen (HBO) therapy in mice with spinal cord injury (SCI). OBJECTIVE: We aimed to explore the intrinsic mechanisms of HBO for SCI through the lens of ferroptosis in the subacute phase. SUMMARY OF BACKGROUND DATA: HBO has been observed to facilitate the restoration of neurological function subsequent to SCI. Ferroptosis is a distinct cellular death mechanism that can be distinguished from apoptosis, necrosis, and autophagy. However, the precise relationship between these two phenomena remains poorly understood. METHODS: We established an SCI model and employed a range of techniques, including behavioral assessments, electron microscopy, immunofluorescence, RT-qPCR, Western blotting (WB), Glutathione (GSH) measurement, and iron assay, to investigate various aspects of HBO therapy on SCI in mice. These included analyzing mitochondrial morphology, neuronal count, GSH levels, iron levels, and the expression of genes (Acyl-CoA synthetase family member-2, Iron-responsive element-binding protein-2) and proteins (Glutathione peroxidase 4; system Xc-light chain) associated with ferroptosis. The study included three groups: Sham-operated, SCI, and HBO. Group comparisons were performed using one-way analysis of variance and one-way repeated measures analysis of variance, followed by Tukey's post hoc test. Statistical significance was set at a P < 0.05. RESULTS: Our findings revealed that HBO therapy significantly enhanced the recovery of lower limb motor function in mice following SCI in the subacute phase. This was accompanied by upregulated expression of GPX4 and system Xc-light chain proteins, elevated GSH levels, increased number of NeuN+ cells, decreased expression of the iron-responsive element-binding protein-2 gene, and reduced iron concentration. CONCLUSIONS: Our research suggests that HBO therapy has the potential to be an effective treatment for SCI in the subacute phase by mitigating ferroptosis.

Activated alkyne-enabled turn-on click bioconjugation with cascade signal amplification for ultrafast and high-throughput antibiotic screening.

Antimicrobial susceptibility testing plays a pivotal role in the discovery of new antibiotics. However, the development of simple, sensitive, and rapid assessment approaches remains challenging. Herein, we report an activated alkyne-based cascade signal amplification strategy for ultrafast and high-throughput antibiotic screening. First of all, a novel water-soluble aggregation-induced emission (AIE) luminogen is synthesized, which contains an activated alkyne group to enable fluorescence turn-on and metal-free click bioconjugation under physiological conditions. Taking advantage of the in-house established method for bacterial lysis, a number of clickable biological substances (i.e., bacterial solutes and debris) are released from the bacterial bodies, which remarkably increases the quantity of analytes. By means of the activated alkyne-mediated turn-on click bioconjugation, the system fluorescence signal is significantly amplified due to the increased labeling sites as well as the AIE effect. Such a cascade signal amplification strategy efficiently improves the detection sensitivity and thus enables ultrafast antimicrobial susceptibility assessment. By integration with a microplate reader, this approach is further applied to high-throughput antibiotic screening.

Hyperbaric Oxygen Treatment in Spinal Cord Injury Recovery: Profiling Long Noncoding RNAs.

STUDY DESIGN: A functional, transcriptome, and long noncoding RNAs (lncRNAs) expression analysis in the spinal cord of mice after hyperbaric oxygen (HBO) treatment. OBJECTIVE: We aimed to explore the mechanism by which HBO treats spinal cord injury (SCI) at the level of lncRNAs. SUMMARY OF BACKGROUND DATA: Immense amounts of research have established that HBO treatment promotes the recovery of neurological function after SCI. The mechanism of action remains to be clarified. METHODS: High-throughput RNA sequencing, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were used to profile lncRNA expression and analyze biological function in the spinal cords of mice from sham-operated, SCI, and HBO-treated groups. The differential expression of lncRNA between the groups was assessed using real-time quantitative polymerase chain reaction. RESULTS: Differential expression across 577 lncRNAs was identified among the three groups. GO analysis showed that free ubiquitin chain polymerization, ubiquitin homeostasis, DNA replication, synthesis of RNA primer, single-stranded telomeric DNA binding, and alpha-amylase activity were significantly enriched. Kyoto Encyclopedia of Genes and Genomes enrichment analysis displayed that vitamin B6 metabolism, one carbon pool by folate, DNA replication, lysine degradation, beta-alanine metabolism, fanconi anemia pathway, and Notch signal pathway were the main pathways with enrichment significance. LncRNAs NONMMUT 092674.1, NONMMUT042986.2, and NONMMUT018850.2 showed significantly different expression between the SCI and the other two groups (P<0.05, <0.01). CONCLUSIONS: This study is the first to determine the expression profiles of lncRNAs in the injured spinal cord after HBO treatment. We identified several important dysregulated lncRNAs in this setting. These results help us better understand the mechanism by which HBO treats SCI and provide new potential therapeutic targets for SCI.

The mechanism by which hyperbaric oxygen treatment alleviates spinal cord injury: genome-wide transcriptome analysis.

Accumulating studies have demonstrated that hyperbaric oxygen (HBO) treatment alleviates spinal cord injury (SCI). However, the underlying mechanism by which HBO alleviates SCI remains to be elucidated. In this study, we performed genome-wide transcriptional profiling of the spinal cord between SCI mice and mice that received HBO treatment by high-throughput RNA sequencing at 1 week after SCI. We also compared genome-wide transcriptional profiles from SCI mice and sham-operated mice. We found 76 differentially co-expressed genes in sham-operated mice, SCI mice, and HBO-treated SCI mice. Using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis, we identified the biological characteristics of these differentially expressed genes from the perspectives of cell component, biological process, and molecular function. We also found enriched functional pathways including ferroptosis, calcium signaling pathway, serotonergic synapse, hypoxia-inducible factor-1 signaling pathway, cholinergic synapse, and neuroactive ligand-receptor interaction. We performed quantitative reverse transcription-polymerase chain reaction and validated that HBO treatment decreased the expression of Hspb1 (heat shock protein beta 1), Hmox1 (heme oxygenase 1), Ftl1 (ferritin light polypeptide 1), Tnc (tenascin C) and Igfbp3 (insulin-like growth factor binding protein 3) and increased the expression of Slc5a7 (solute carrier family 5 choline transporter member 7) after SCI. These results revealed the genome-wide transcriptional profile of the injured spinal cord after HBO treatment. Our findings contribute to a better understanding of the mechanism by which HBO treats SCI and may provide new targets for SCI intervention.

A receptor-targeting AIE photosensitizer for selective bacterial killing and real-time monitoring of photodynamic therapy outcome.

A receptor-targeting AIE photosensitizer (CE-TPA) is synthesized by conjugating cephalothin with a cationic D-A type AIE photosensitizer for selective killing of Gram-positive bacteria over Gram-negative bacteria and normal mammalian cells. By virtue of the strong photosensitization capability, CE-TPA exhibits efficient killing against Gram-positive methicillin-resistant Staphylococcus aureus. More importantly, the photodynamic bactericidal outcome can be conveniently reflected in a real-time fashion by the polarity-sensitive property of CE-TPA.

TangShenWeiNing Formula Prevents Diabetic Nephropathy by Protecting Podocytes Through the SIRT1/HIF-1α Pathway.

Background: Diabetic nephropathy (DN) represents a major complication of diabetes, and podocyte injury has a critical function in DN development. TangShenWeiNing formula (TSWN) has been demonstrated to efficiently decrease proteinuria and protect podocytes in DN. This work aimed to explore the mechanism by which TSWN alleviates DN and protects podocytes. Methods: The major bioactive components of TSWN were detected by mass spectrometry (MS) and pharmacological databases. Eight-week-old male C57BLKS/J db/m and db/db mice were provided pure water, valsartan, low dose TSWN, middle dose TSWN and high dose TSWN by gavage for 12 weeks, respectively. Results: MS and network pharmacology analyses suggested that TSWN might prevent DN through the sirtuin (SIRT)1/hypoxia-inducible factor (HIF)-1α pathway. Diabetic mice showed elevated urinary albumin in comparison with non-diabetic mice, and TSWN decreased urinary albumin in diabetic mice. Histological injury increased in the kidney in diabetic mice, which could be improved by TSWN. Fibrosis and collagen I expression were induced in the diabetic mouse kidney in comparison with the non-diabetic mouse kidney; TSWN alleviated these effects. Apoptosis and cleaved caspase-3 were induced in the diabetic mouse kidney in comparison with the non-diabetic mouse kidney, and TSWN blunted these effects. Podocytes were damaged in the diabetic mouse kidney, which was improved by TSWN. Podocin and nephrin amounts were decreased in the diabetic mouse kidney in comparison with the non-diabetic mouse kidney, and podocalyxin was increased in urine of diabetic animals in comparison with non-diabetic counterparts. After TSWN treatment, podocin and nephrin were raised in the diabetic mouse kidney, and urinary podocalyxin was depressed in diabetic animals. Diabetic mice had lower SIRT1 and higher HIF-1α amounts in kidney specimens in comparison with non-diabetic mice, and TSWN promoted SIRT1 and inhibited HIF-1α in the diabetic mouse kidney. Moreover, co-staining of SIRT1 and podocin revealed that SIRT1 decreased in podocytes from diabetic mice in comparison with those from non-diabetic mice, and TSWN elevated SIRT1 in podocytes. Conclusions: This study indicated that TSWN alleviates DN by improving podocyte injury through the SIRT1/HIF-1α pathway in diabetic mouse kidneys.

Room-Temperature Harvesting Oxidase-Mimicking Enzymes with Exogenous ROS Generation in One Step.

Despite the advantages of low cost, high stability, and activities, a majority of nanozymes rely on strict synthesis conditions and precise size/structure control, hindering the stable, bulk, and high-yield production that is necessary for general use. To facilitate the transition of nanozymes from benchtop to real-world applications, we herein present a one-step approach, which only needs mixing of two broad commercialized reagents at room temperature, to harvest gold nanoparticles-bovine serum albumin (BSA) nanocomposite (BSA-Au) with distinct oxidase-like activity and good stability in a broad range of harsh conditions. Density functional theory (DFT) calculations demonstrate the oxidase-like activity of BSA-Au stemming from thermodynamically and kinetically favored facets for O2 activation. The reactive oxygen species (ROS) generation of BSA-Au contributes to the catalytic activities and further enables water sterilization and antibacterial applications against superbugs. This one-step strategy promises great potential in bulk production of nanozyme for broad application beyond laboratory use.

Do sandwich vertebral bodies increase the risk of post-augmentation fractures? A retrospective cohort study.

Until now, there have been only a few retrospective studies that focused on the outcomes of sandwich vertebral bodies (SVBs). This is a long-term retrospective cohort study to investigate the SVBs. We found that although patients with SVBs had a relatively high risk of developing new fractures after VA, the incidence rate of new fractures was not significantly different from that of the control group. However, the statistical power of this study was very limited. Therefore, and because the refracture rate in these patients is substantial, routine long-term monitoring of patients after VA for osteoporosis is strongly recommended. BACKGROUND: Sandwich vertebral bodies (SVBs) are intact unaugmented vertebral bodies between two previously augmented vertebrae. Until recently, only a few studies have reported the outcomes and strategies for SVBs. This retrospective cohort study aimed to describe the clinical features and incidence of new fractures in patients with SVBs. METHODS: The clinical data were collected from 179 patients with 237 symptomatic osteoporotic vertebral compression fractures who underwent vertebral augmentation (VA). Among them, 23 patients with 24 levels of SVBs were included. Spinal radiographs (X-ray and CT) of all patients were evaluated prior to surgery 1 day after primary VA and during follow-up. RESULTS: All patients successfully underwent PKP with an average follow-up period of 21.48 months. Asymptomatic cement leakage occurred in four patients (17.4%), and eight patients (34.8%) developed new fractures following primary PKP, including four sandwich, six adjacent, four remote vertebral fractures, and one re-collapse of cemented vertebrae. The incidence of new fractures in the SVB and control groups was 16.7% (4/24) and 13.0% (6/46), respectively, but there was no significant difference. CONCLUSIONS: Although patients with SVBs had a relatively high risk of developing new fractures after VA, the incidence rate of new fractures was not significantly different from that of the control group. However, the statistical power of this study was very limited. Therefore, and because the refracture rate in these patients is substantial, routine long-term monitoring of patients after VA for osteoporosis is strongly recommended.

PPAR-α Agonist Fenofibrate Prevented Diabetic Nephropathy by Inhibiting M1 Macrophages via Improving Endothelial Cell Function in db/db Mice.

Background: Diabetic nephropathy (DN) is one of the major diabetic microvascular complications, and macrophage polarization plays a key role in the development of DN. Endothelial cells regulate macrophage polarization. Peroxisome proliferator-activated receptor (PPAR)-α agonists were demonstrated to prevent DN and improve endothelial function. In this study, we aimed to investigate whether PPAR-α agonists prevented DN through regulating macrophage phenotype via improving endothelial cell function. Methods: Eight-week-old male C57BLKS/J db/m and db/db mice were given fenofibrate or 1% sodium carboxyl methylcellulose by gavage for 12 weeks. Results: Db/db mice presented higher urinary albumin-to-creatinine ratio (UACR) than db/m mice, and fenofibrate decreased UACR in db/db mice. Fibrosis and collagen I were elevated in db/db mouse kidneys compared with db/m mouse kidneys; however, they were decreased after fenofibrate treatment in db/db mouse kidneys. Apoptosis and cleaved caspase-3 were enhanced in db/db mouse kidneys compared to db/m mouse kidneys, while fenofibrate decreased them in db/db mouse kidneys. Db/db mice had a suppression of p-endothelial nitric oxide synthase (eNOS)/t-eNOS and nitric oxide (NO), and an increase of angiopoietin-2 and reactive oxygen species (ROS) in kidneys compared with db/m mice, and fenofibrate increased p-eNOS/t-eNOS and NO, and decreased angiopoietin-2 and ROS in db/db mouse kidneys. Hypoxia-inducible factor (HIF)-1α and Notch1 were promoted in db/db mouse kidneys compared with db/m mouse kidneys, and were reduced after fenofibrate treatment in db/db mouse kidneys. Furthermore, the immunofluorescence staining indicated that M1 macrophage recruitment was enhanced in db/db mouse kidneys compared to db/m mouse kidneys, and this was accompanied by a significant increase of tumor necrosis factor (TNF)-α and interleukin (IL)-1ß in kidneys and in serum of db/db mice compared with db/m mice. However, fenofibrate inhibited the renal M1 macrophage recruitment and cytokines associated with M1 macrophages in db/db mice. Conclusions: Our study indicated that M1 macrophage recruitment due to the upregulated HIF-1α/Notch1 pathway induced by endothelial cell dysfunction involved in type 2 diabetic mouse renal injury, and PPAR-α agonist fenofibrate prevented DN by reducing M1 macrophage recruitment via inhibiting HIF-1α/Notch1 pathway regulated by endothelial cell function in type 2 diabetic mouse kidneys.

Composite Film with Antibacterial Gold Nanoparticles and Silk Fibroin for Treating Multidrug-Resistant E. coli-Infected Wounds.

The progressively increasing degree of multiple antibiotic resistance in Gram-negative bacteria challenges the treatment of severe bacterial infection-induced chronic skin wounds. To address this problem, we developed a straightforward strategy to prepare a composite film consisting of antibacterial nanoparticles (4,6-diamino-2-pyrimidinethiol-functionalized gold nanoparticles, DAPT-Au NPs) and a silk fibroin (SF) mixed-matrix membrane (DAPT-Au-SF MMM) as a wound dressing for treating multidrug-resistant (MDR) E. coli- induced infection. The good hydrophilicity of SF allows the highly effective release of DAPT-Au NPs from the composite film to combat pathogens within minutes. The antibacterial activity of the composite film is maintained regardless of antimicrobial susceptibility. DAPT-Au-SF MMMs also promote healing in rat wounds infected by clinically isolated MDR E. coli. Our findings provide a new strategy to extend the use of gold nanomaterials and SF-based wound dressings, especially against drug-resistant bacterial infections.

Posterior thoracolumbar hemivertebra resection and short-segment fusion in congenital scoliosis: surgical outcomes and complications with more than 5-year follow-up.

BACKGROUND: Treatment of congenital hemivertebra is challenging and data on long-term follow-up (≥ 5 years) are lacking. This study evaluated the surgical outcomes of posterior thoracolumbar hemivertebra resection and short-segment fusion with pedicle screw fixation for treatment of congenital scoliosis with over 5-year follow-up. METHODS: This study evaluated 27 consecutive patients with congenital scoliosis who underwent posterior thoracolumbar hemivertebra resection and short-segment fusion from January 2007 to January 2015. Segmental scoliosis, total main scoliosis, compensatory cranial curve, compensatory caudal curve, trunk shift, shoulder balance, segmental kyphosis, and sagittal balance were measured on radiographs. Radiographic outcomes and all intraoperative and postoperative complications were recorded. RESULTS: The segmental main curve was 40.35° preoperatively, 11.94° postoperatively, and 13.24° at final follow-up, with an average correction of 65.9%. The total main curve was 43.39° preoperatively, 14.13° postoperatively, and 16.06° at final follow-up, with an average correction of 60.2%. The caudal and cranial compensatory curves were corrected from 15.78° and 13.21° to 3.57° and 6.83° postoperatively and 4.38° and 7.65° at final follow-up, with an average correction of 69.2% and 30.3%, respectively. The segmental kyphosis was corrected from 34.30° to 15.88° postoperatively and 15.12° at final follow-up, with an average correction of 61.9%. A significant correction (p < 0.001) in segmental scoliosis, total main curve, caudal compensatory curves and segmental kyphosis was observed from preoperative to the final follow-up. The correction in the compensatory cranial curve was significant between preoperative and postoperative and 2-year follow-up (p < 0.001), but a statistically significant difference was not observed between the preoperative and final follow-up (p > 0.001). There were two implant migrations, two postoperative curve progressions, five cases of proximal junctional kyphosis, and four cases of adding-on phenomena. CONCLUSION: Posterior thoracolumbar hemivertebra resection after short-segment fusion with pedicle screw fixation in congenital scoliosis is a safe and effective method for treatment and can achieve rigid fixation and deformity correction.

Ferroptosis Enhanced Diabetic Renal Tubular Injury via HIF-1α/HO-1 Pathway in db/db Mice.

Background: Ferroptosis is a recently identified iron-dependent form of cell death as a result of increased reactive oxygen species (ROS) and lipid peroxidation. In this study, we investigated whether ferroptosis aggravated diabetic nephropathy (DN) and damaged renal tubules through hypoxia-inducible factor (HIF)-1α/heme oxygenase (HO)-1 pathway in db/db mice. Methods: Db/db mice were administered with or without ferroptosis inhibitor Ferrostatin-1 treatment, and were compared with db/m mice. Results: Db/db mice showed higher urinary albumin-to-creatinine ratio (UACR) than db/m mice, and Ferrostatin-1 reduced UACR in db/db mice. Db/db mice presented higher kidney injury molecular-1 and neutrophil gelatinase-associated lipocalin in kidneys and urine compared to db/m mice, with renal tubular basement membranes folding and faulting. However, these changes were ameliorated in db/db mice after Ferrostatin-1 treatment. Fibrosis area and collagen I were promoted in db/db mouse kidneys as compared to db/m mouse kidneys, which was alleviated by Ferrostatin-1 in db/db mouse kidneys. HIF-1α and HO-1 were increased in db/db mouse kidneys compared with db/m mouse kidneys, and Ferrostatin-1 decreased HIF-1α and HO-1 in db/db mouse kidneys. Iron content was elevated in db/db mouse renal tubules compared with db/m mouse renal tubules, and was relieved in renal tubules of db/db mice after Ferrostatin-1 treatment. Ferritin was increased in db/db mouse kidneys compared with db/m mouse kidneys, but Ferrostatin-1 reduced ferritin in kidneys of db/db mice. Diabetes accelerated nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-derived ROS formation in mouse kidneys, but Ferrostatin-1 prevented ROS formation derived by NADPH oxidases in db/db mouse kidneys. The increased malondialdehyde (MDA) and the decreased superoxide dismutase (SOD), catalase (CAT), glutathione peroxidases (GSH-Px) were detected in db/db mouse kidneys compared to db/m mouse kidneys, whereas Ferrostatin-1 suppressed MDA and elevated SOD, CAT, and GSH-Px in db/db mouse kidneys. Glutathione peroxidase 4 was lower in db/db mouse kidneys than db/m mouse kidneys, and was exacerbated by Ferrostatin-1 in kidneys of db/db mice. Conclusions: Our study indicated that ferroptosis might enhance DN and damage renal tubules in diabetic models through HIF-1α/HO-1 pathway.

Risk factors of cemented vertebral refracture after percutaneous vertebral augmentation: a systematic review and meta-analysis.

To evaluate the risk factors of cemented vertebral refracture after percutaneous vertebral augmentation (PVA) for patients with osteoporotic vertebral compression fractures (OVCFs). We performed a literature search on cemented vertebral refracture after PVA using the PubMed, EMBASE, and Cochrane Library medical databases. The clinical data, including literature information, basic patient information, observational factors, and interventional factors, were extracted by two authors. The pooled results and related heterogeneity of each factor between the refracture group and the non-refracture group were evaluated using Review Manager software 5.35. A total of 3185 patients from 10 studies were included, with 195 patients in the refracture group and 2990 patients in the non-refracture group. The mean follow-up duration was 18.9 months. According to the meta-analysis, age, low bone marrow density (BMD), intravertebral cleft (IVC), high anterior vertebral height (AVH) restoration/high Cobb angle restoration, and low cement dose were the risk factors of cemented vertebral refracture after PVA. Our results showed that age, low BMD, IVC, high AVH restoration, high Cobb angle restoration, and low cement dose were the risk factors for cemented vertebral refracture after PVA.

2D AuPd alloy nanosheets: one-step synthesis as imaging-guided photonic nano-antibiotics.

The complicated synthesis and undesirable biocompatibility of nanomaterials hinder the synergistic photothermal/photodynamic therapy for bacterial infections. Herein, we develop a one-step preparation method of 2D AuPd alloy nanosheets as imaging-guided photonic nano-antibiotics. 2D AuPd alloy nanosheets with an extremely small thickness (∼1.5 nm) exhibit prominent photothermal effects (η = 76.6%), excellent ROS generation, strong photoacoustic signals and desirable biocompatibility. AuPd nanosheets can eliminate 100% of representative Gram-positive (Staphylococcus aureus) and Gram-negative bacteria (Escherichia coli) when irradiated using an 808 nm laser at 1 W cm-2 for 5 minutes. After being modified with a bacterial targeting peptide, under the guidance of photoacoustic imaging, AuPd nanosheets achieve promising synergistic photothermal/photodynamic therapeutic efficacy in treating Staphylococcus aureus infected mice. This work expands the biomedical application of 2D noble metal nanomaterials to the field of photonic nano-antibiotics.

Albumin Broadens the Antibacterial Capabilities of Nonantibiotic Small Molecule-Capped Gold Nanoparticles.

Nonantibiotic small molecule-modified gold nanoparticles (Au NPs) show great potential as an alternative for commercial antibiotics, yet their narrow antibacterial spectrum hinders the wide application in clinics. We observe that Au NPs cofunctionalized with both bovine serum albumin (BSA) and 4,6-diamino-2-pyrimidinethiol (DAPT) can generate conjugates (Au_DAPT_BSA) with progressive antimicrobial activities, including decreased minimal inhibitory concentration against Gram-negative bacteria and extended antibacterial spectrum against Gram-positive bacteria compared with DAPT-capped Au NPs (Au_DAPT). Au_DAPT_BSA induces no drug resistance and can significantly decrease the number of bacteria in the biofilms formed by Pseudomonas aeruginosa and Staphylococcus aureus. In addition, Au_DAPT_BSA exhibit in vivo healing efficiency for mice with subcutaneous abscesses caused by clinically isolated, multidrug resistant Escherichia coli or S. aureus without inducing detectable toxicity to the mammalian cells/animals. Our findings provide a new strategy for strengthening nanomaterial-based bactericides such as Au NPs, especially against drug-resistant bacterial infections.

Blocking-Free ELISA Using a Gold Nanoparticle Layer Coated Commercial Microwell Plate.

Enzyme-linked immunosorbent assays (ELISA) show extensive application in immunoassays, to detect and monitor protein biomarkers in clinical diagnosis. Nevertheless, the time required and its multiple steps limit its application. We take advantage of a polyethyleneimine (PEI) gold nanoparticle (GNP) coated microwell plate to perform blocking-free ELISA, in which no nonspecific protein adsorption appears on the GNP layer. If the PEI-GNP coated microwell plate and immobilization of captured antibodies on the plate are prepared in advance, such as using an ELISA kit, the whole ELISA process can be finished in less than 2 h. Meanwhile, we have ensured that the GNP layer can preserve the precision and good linearity of ELISA without causing negative effects on the plate.

Extraordinarily thick-boned fish linked to the aridification of the Qaidam Basin (northern Tibetan Plateau).

Scattered with numerous salt lakes and approximately 2,700-3,200 m above sea level, the giant Qaidam inland basin on the northern Tibetan Plateau has experienced continuing aridification since the beginning of the Late Cenozoic as a result of the India-Asia plate collision and associated uplift of the Tibetan Plateau. Previous evidence of aridification comes mainly from evaporite deposits and salinity-tolerant invertebrate fossils. Vertebrate fossils were rare until recent discoveries of abundant fish. Here, we report an unusual cyprinid fish, Hsianwenia wui, gen. et sp. nov., from Pliocene lake deposits of the Qaidam Basin, characterized by an extraordinarily thick skeleton that occupied almost the entire body. Such enormous skeletal thickening, apparently leaving little room for muscles, is unknown among extant fish. However, an almost identical condition occurs in the much smaller cyprinodontid Aphanius crassicaudus (Cyprinodonyiformes), collected from evaporites exposed along the northern margins of the Mediterranean Sea during the Messinian desiccation period. H. wui and A. crassicaudus both occur in similar deposits rich in carbonates (CaCO(3)) and sulfates (CaSO(4)), indicating that both were adapted to the extreme conditions resulting from the aridification in the two areas. The overall skeletal thickening was most likely formed through deposition of the oversaturated calcium and was apparently a normal feature of the biology and growth of these fish.