Molecular insights into degron recognition by CRL5ASB7 ubiquitin ligase.

The ankyrin (ANK) SOCS box (ASB) family, encompassing ASB1-18, is the largest group of substrate receptors of cullin 5 Ring E3 ubiquitin ligase. Nonetheless, the mechanism of substrate recognition by ASB family proteins has remained largely elusive. Here we present the crystal structure of ASB7-Elongin B-Elongin C ternary complex bound to a conserved helical degron. ASB7 employs its ANK3-6 to form an extended groove, effectively interacting with the internal α-helix-degron through a network of side-chain-mediated electrostatic and hydrophobic interactions. Our structural findings, combined with biochemical and cellular analyses, identify the key residues of the degron motif and ASB7 required for their recognition. This will facilitate the identification of additional physiological substrates of ASB7 by providing a defined degron motif for screening. Furthermore, the structural insights provide a basis for the rational design of compounds that can specifically target ASB7 by disrupting its interaction with its cognate degron.

Construction of yeast microbial consortia for petroleum hydrocarbons degradation.

Microbial degradation of petroleum hydrocarbons plays a vital role in mitigating petroleum contamination and heavy oil extraction. In this study, a Saccharomyces cerevisiae capable of degrading hexadecane has been successfully engineered, achieving a maximum degradation rate of up to 20.42%. However, the degradation ability of this strain decreased under various pressure conditions such as high temperature, high osmotic pressure, and acidity conditions. Therefore, a S. cerevisiae with high tolerance to these conditions has been constructed. And then, we constructed an "anti-stress hydrocarbon-degrading" consortium comprising engineered yeast strain SAH03, which degrades hexadecane, and glutathione synthetic yeast YGSH10, which provides stress resistance. This consortium was able to restore the degradation ability of SAH03 under various pressure conditions, particularly exhibiting a significant increase in degradation rate from 5.04% to 17.04% under high osmotic pressure. This study offers a novel approach for improving microbial degradation of petroleum hydrocarbons.

Effect of initial ammonium concentration on a one-stage partial nitrification/anammox biofilm system: Nitrogen removal performance and the microbial community.

One-stage partial nitrification coupled with anammox (PN/A) technology effectively reduces the energy consumption of a biological nitrogen removal system. Inhibiting nitrite-oxidizing bacteria (NOB) is essential for this technology to maintain efficient nitrogen removal performance. Initial ammonium concentration (IAC) affects the degree of inhibited NOB. In this study, the effect of the IAC on a PN/A biofilm was investigated in a moving bed biofilm reactor. The results showed that nitrogen removal efficiency decreased from 82.49% ± 1.90% to 64.57% ± 3.96% after the IAC was reduced from 60 to 20 mg N/L, while the nitrate production ratio increased from 13.87% ± 0.90% to 26.50% ± 3.76%. NOB activity increased to 1,133.86 mg N/m2/day after the IAC decreased, approximately 4-fold, indicating that the IAC plays an important inhibitory role in NOB. The rate-limiting step in the mature biofilm of the PN/A system is the nitritation process and is not shifted by the IAC. The analysis of the microbial community structure in the biofilm indicates that the IAC was the dominant factor in changes in community structure. Ca. Brocadia and Ca. Jettenia were the main anammox bacteria, and Nitrosomonas and Nitrospira were the main AOB and NOB, respectively. IAC did not affect the difference in growth between Ca. Brocadia and Ca. Jettenia. Thus, modulating the IAC promoted the PN/A process with efficient nitrogen removal performance at medium to low ammonium concentrations.

Ultra-Thin and Broadband P-Band Metamaterial Absorber Based on Carbonyl Iron Powder Composites.

The field of P-band (0.3-1 GHz) absorption has witnessed rapid development in metamaterial absorbers due to their exceptional designability and the absence of restrictions imposed by the one-fourth wavelength rule. In this study, we combined carbonyl iron powder (CIP) composites with a periodic structure composed of metal capacitive patterns and employed a genetic algorithm (GA) to optimize the electromagnetic parameters of the CIP substrate. By selecting the appropriate shape and material for the units of pattern based on transmission line theory, as well as regulating relevant structural parameters, we successfully designed an ultra-thin broadband metamaterial absorber for the P-band. Experimental results demonstrate that within the range of 0.3-0.85 GHz, the reflection loss of our absorber remains below -5 dB, with a maximum value of -9.54 dB occurring at 0.45 GHz. Remarkably, this absorber possesses a thickness equivalent to only 1/293 of its working wavelength. Then, we conducted analyses on electric field distribution, magnetic field distribution, and energy loss density. Our findings suggest that high-performance absorption in metamaterials can be attributed to λ/4 resonant or coupling effects between structural units or diffraction phenomena. This absorber offers several advantages, including broad low-frequency absorption capability, ultra-thin profile, and convenient fabrication process, thus providing valuable theoretical insights for designing metamaterial structures.

An Electronic Health Record Alert for Inpatient Coronavirus Disease 2019 Vaccinations Increases Vaccination Ordering and Uncovers Workflow Inefficiencies.

BACKGROUND: Despite mortality benefits, only 19.9% of U.S. adults are fully vaccinated against the coronavirus disease 2019 (COVID-19). The inpatient setting is an opportune environment to update vaccinations, and inpatient electronic health record (EHR) alerts have been shown to increase vaccination rates. OBJECTIVE: Our objective was to evaluate whether an EHR alert could increase COVID-19 vaccinations in eligible hospitalized adults by prompting providers to order the vaccine. METHODS: This was a quasiexperimental pre-post-interventional design study at an academic and community hospital in the western United States between 1 January, 2021 and 31 October, 2021. Inclusion criteria were unvaccinated hospitalized adults. A soft-stop, interruptive EHR alert prompted providers to order COVID-19 vaccines for those with an expected discharge date within 48 hours and interest in vaccination. The outcome measured was the proportion of all eligible patients for whom vaccines were ordered and administered before and after alert implementation. RESULTS: Vaccine ordering rates increased from 4.0 to 13.0% at the academic hospital (odds ratio [OR]: 4.01, 95% confidence interval [CI]: 3.39-4.74, p < 0.001) and from 7.4 to 11.6% at the community hospital (OR: 1.62, 95% CI: 1.23-2.13, p < 0.001) after alert implementation. Administration increased postalert from 3.6 to 12.7% at the academic hospital (OR: 3.21, 95% CI: 2.70-3.82, p < 0.001) but was unchanged at the community hospital, 6.7 to 6.7% (OR: 0.99, 95% CI: 0.73-1.37, p = 0.994). Further analysis revealed infrequent vaccine availability at the community hospital. CONCLUSION: Vaccine ordering rates improved at both sites after alert implementation. Vaccine administration rates, however, only improved at the academic hospital, likely due in part to vaccine dispensation inefficiency at the community hospital. This study demonstrates the potential impact of complex workflow patterns on new EHR alert success and provides a rationale for subsequent qualitative workflow analysis with alert implementation.

PdMo bimetallene nanozymes for photothermally enhanced antibacterial therapy and accelerated wound healing.

Although antibacterial platforms involving nanozymes have been extensively investigated, there are still problems of poor reactive oxygen species generation efficiency and obstinate bacterial biofilms. Developing a nanozyme-photothermal therapy nanoplatform with superior sterilization effects and minimal side effects would be a good alternative for completely eliminating bacteria and biofilms. Herein, an ultrathin PdMo bimetallene nanozyme with a planar topology and boosted metal utilization, exhibiting excellent photothermal and peroxidase-like activity, is designed for synergistic nanozyme-photothermal sterilization applications and accelerated wound healing. The superior catalytic activity of PdMo bimetallene nanozymes could convert a biosafe concentration of hydrogen peroxide (H2O2) into large quantities of toxic hydroxyl radicals (•OH) under laser irradiation, enhancing bacterial membrane permeability and thermal sensitivity for efficient removal of bacteria and biofilms. In addition, PdMo bimetallene presents a good wound-healing ability according to the results of fibroblast proliferation and collagen deposition with minor side effects. This work would provide an innovative avenue for developing metallene-based nanozymes for biomedical applications.

Blockade of IL-11 Trans-Signaling or JAK2/STAT3 Signaling Ameliorates the Profibrotic Effect of IL-11.

OBJECTIVES: Systemic sclerosis (SSc) is a rare rheumatic disease characterized by vascular damage, dysregulated immune response, and fibrosis. Interleukin-11 (IL-11) is upregulated in SSc. This study aimed to investigate the pathological and therapeutic role of the IL-11 trans-signaling pathway in SSc. METHODS: Plasma IL-11 level was evaluated in 32 patients with SSc and 15 healthy controls, while the expression levels of ADAM10, ADAM17, IL-11, IL-11 Rα, or IL-11 co-stained with CD3 or CD163 in the skin of SSc patients and healthy controls were analyzed. Fibroblasts were treated with IL-11 and ionomycin to evaluate the profibrotic effect of IL-11 trans-signaling pathway. TJ301 (sgp130Fc) and WP1066 (a JAK2/STAT3 inhibitor) intervention groups were set up to investigate the antifibrotic effect of targeting IL-11. RESULTS: Levels of plasma IL-11 were extremely low in most SSc patients and healthy controls. In contrast, levels of IL-11, IL-11 Rα, and ADAM10, but not ADAM17, were significantly elevated in the skin of SSc patients. Moreover, the numbers of IL-11+ CD3+ cells and IL-11+ CD163+ cells were increased in the skin of SSc patients. Besides, IL-11 and ADAM10 were also elevated in the skin and pulmonary of bleomycin-induced SSc mouse. Fibroblasts co-stimulated with IL-11 and ionomycin showed increased expression of COL3 and phosphorylation of STAT3, which could be inhibited by TJ301 or WP1066. TJ301 also ameliorated skin and lung fibrosis in BLM-induced SSc mouse. CONCLUSIONS: IL-11 induces fibrosis in SSc by regulating the trans-signaling pathway. Blockage of sgp130Fc or inhibition of the JAK2/STAT3 pathway could ameliorate the profibrotic effect of IL-11.

High Contrast Detection of Carotid Neothrombus with Strong Near-Infrared Absorption Selenium Nanosphere Enhanced Photoacoustic Imaging.

Background: Carotid artery thrombosis is the leading cause of stroke. Since there are no apparent symptoms in the early stages of carotid atherosclerosis onset, it causes a more significant clinical diagnosis. Photoacoustic (PA) imaging provides high contrast and good depth information, which has been used for the early detection and diagnosis of many diseases. Methods: We investigated thrombus formation by using 20% ferric chloride (FeCl3) in the carotid arteries of KM mice for the thrombosis model. The near-infrared selenium/polypyrrole (Se@PPy) nanomaterials are easy to synthesize and have excellent optical absorption in vivo, which can be used as PA contrast agents to obtain thrombosis information. Results: In vitro experiments showed that Se@PPy nanocomposites have fulfilling PA ability in the 700 nm to 900 nm wavelength range. In the carotid atherosclerosis model, maximum PA signal enhancement up to 3.44, 4.04, and 5.07 times was observed by injection of Se@PPy nanomaterials, which helped to diagnose the severity of carotid atherosclerosis. Conclusion: The superior PA signal of Se@PPy nanomaterials can identify the extent of atherosclerotic carotid lesions, demonstrating the feasibility of PA imaging technology in diagnosing carotid thrombosis lesion formation. This study demonstrates nanocomposites and PA techniques for imaging and diagnosing carotid thrombosis in vivo.

Visualizing the early-stage testicular torsion by dual-modal photoacoustic and ultrasound imaging.

Delayed treatment of testicular torsion (TT) can lead to permanent loss of reproductive capacity. Photoacoustic imaging (PAI) and ultrasound imaging (USI) was tested for detecting TT at early stage in mice based on PAI-obtained oxygen saturation (sO2), and USI-collected color pixel density (CPD), peak systolic velocity (PSV) and resistance index (RI). For complete TT, both CPD (9.08 % ± 3.084 to almost zero) and sO2 data (70.09 % ± 1.656-59.84 % ± 1.427) showed an significant change 2 h post-torsion. For incomplete TT, sO2 data exhibited a strong time relationship (Mean values: 6 h, 64.83 % ± 1.898; 12 h, 60.67 % ± 3.555; 24 h, 57.85 % ± 3.575; P < 0.05). However, USI-collected CPD, PSV or IR data from the same TT models showed no significant difference. This study indicated that USI and PAI could identify complete TT. Meanwhile, PAI has shown great potential in the diagnosis of incomplete TT within 24 h based on time-related sO2 map.

Dachengqi Decoction alleviates intestinal inflammation in ovalbumin-induced asthma by reducing group 2 innate lymphoid cells in a microbiota-dependent manner.

Background and aim: Dachengqi Decoction (DCQD) as a classic traditional Chinese medicine has been reported to be effective in treating asthma, but its mechanism remains unknown. This study aimed to reveal the mechanisms of DCQD on the intestinal complications of asthma mediated by group 2 innate lymphoid cells (ILC2) and intestinal microbiota. Experimental procedure: Ovalbumin (OVA) was used to construct asthmatic murine models. IgE, cytokines (e.g., IL-4, IL-5), fecal water content, colonic length, histopathologic appearance, and gut microbiota were evaluated in asthmatic mice treated with DCQD. Finally, we administered DCQD to antibiotic-treated asthmatic mice to measure the ILC2 in the small intestine and colon. Results and conclusion: DCQD decreased pulmonary IgE, IL-4, and IL-5 levels in asthmatic mice. The fecal water content, the colonic length weight loss, and the epithelial damage of jejunum, ileum, and colon of asthmatic mice were ameliorated by DCQD. Meanwhile, DCQD greatly improved intestinal dysbiosis by enriching Allobaculum, Romboutsia and Turicibacter in the whole intestine, and Lactobacillus gasseri only in the colon. However, DCQD caused less abundant Faecalibaculum and Lactobacillus vaginalis in the small intestine of asthmatic mice. A higher ILC2 proportion in different gut segments of asthmatic mice was reversed by DCQD. Finally, significant correlations appeared between DCQD-mediated specific bacteria and cytokines (e.g., IL-4, IL-5) or ILC2. These findings indicate that DCQD alleviated the concurrent intestinal inflammation in OVA-induced asthma by decreasing the excessive accumulation of intestinal ILC2 in a microbiota-dependent manner across different gut locations.

Effect of thermal hydrolyzed sludge filtrate as an external carbon source on biological nutrient removal performance of A2/O system.

Thermal hydrolyzed sludge filtrate (THSF) rich in biodegradable organics could be a promising external carbon source for biological nutrient removal (BNR). The use of THSF can effectively reduce wastewater treatment plants operating costs and recover bioresources and bioenergy from the waste activated sludge. In this study, the effect of THSF on the BNR process was investigated using a lab-scale anaerobic/anoxic/oxic (A2/O) system. Total nitrogen (TN) and total phosphorus (TP) removal efficiencies of 74.26 ± 3.36% and 92.20 ± 3.13% at a 0.3% dosing ratio were achieved, respectively. Moreover, 20.42% of the chemical oxygen demand (COD) contained in THSF contributed to denitrification, enhancing nitrogen removal efficiency from 55.30 to 74.26%. However, the effluent COD increased by approximately 36.80%, due to 18.39% of the COD contained in THSF discharged with effluent. In addition, the maximum denitrification rate was approximately 16.01 mg N g VSS-1 h-1, while the nitrification rate was not significantly affected by THSF. Nitrosomonas, a common chemoautotrophic nitrifier, was not detected after the introduction of THSF. The aerobic denitrifier Rubellimicrobium was stimulated, and its relative abundance increased from 0.16 to 3.03%. Moreover, the relative abundance of Dechloromonas was 3.93%, indicating that the denitrifying phosphorus removal process was enhanced. This study proposes an engineering application route of THSF, and the chemical phosphate removal pretreatment might be a means to suppress the phosphate recirculation.

CRISPR-based targeted haplotype-resolved assembly of a megabase region.

Constructing high-quality haplotype-resolved genome assemblies has substantially improved the ability to detect and characterize genetic variants. A targeted approach providing readily access to the rich information from haplotype-resolved genome assemblies will be appealing to groups of basic researchers and medical scientists focused on specific genomic regions. Here, using the 4.5 megabase, notoriously difficult-to-assemble major histocompatibility complex (MHC) region as an example, we demonstrated an approach to construct haplotype-resolved assembly of the targeted genomic region with the CRISPR-based enrichment. Compared to the results from haplotype-resolved genome assembly, our targeted approach achieved comparable completeness and accuracy with reduced computing complexity, sequencing cost, as well as the amount of starting materials. Moreover, using the targeted assembled personal MHC haplotypes as the reference both improves the quantification accuracy for sequencing data and enables allele-specific functional genomics analyses of the MHC region. Given its highly efficient use of resources, our approach can greatly facilitate population genetic studies of targeted regions, and may pave a new way to elucidate the molecular mechanisms in disease etiology.

Bio-Based Waterborne Polyurethane Coatings with High Transparency, Antismudge and Anticorrosive Properties.

Green and environment-friendly preparation are of the utmost relevance to the development of transparent antismudge coatings. To prepare a waterborne polyurethane (WPU) coating with antismudge property, it is challenging to balance the stability of dispersion and the antismudge property of coating. Herein, we prepare a transparent bio-based WPU coating grafted with a minor proportion of poly(dimethylsiloxane) (WPU-g-PDMS) using renewable castor oil, monocarbinol-terminated PDMS, hexamethylene diisocyanate trimer, and 2,2-bis(hydroxymethyl)propionic acid as raw materials. Effects of the dosage of monocarbinol-terminated PDMS, the curing temperature, and the curing time on the antismudge performance were studied. Results showed that rigorous stirring (3000 rpm) is necessary to obtain a stable WPU-g-PDMS dispersion with a storage time longer than 6 months. A high curing temperature (>160 °C) and a period of curing time (>1 h) are indispensable to obtain the excellent antismudge property because they would facilitate the grafted low-surface-tension PDMS chains to migrate from the interior to the coating surface. The facts that simulated contaminated liquids such as water, HCl solution, NaOH solution, artificial blood, and tissue fluid could slide off easily and cleanly, and marker ink lined on the coating surface could shrink, indicated that the WPU-g-PDMS coating has good antismudge properties, which could be self-compensated shortly after deterioration. Due to the high cross-linking degree caused by multifunctional polyol and isocyanate, the WPU-g-PDMS coating has high hardness and good anticorrosive performance. The antismudge functionalization and waterborne technology of bio-based polyurethane coatings proposed in this work could be a promising contribution to the green and sustainable development of functional coatings. This kind of WPU-g-PDMS coating is expected to protect and decorate electronic screens, vehicles, and buildings, especially endoscopes.

SEMI-ROLLED LEAF 10 stabilizes catalase isozyme B to regulate leaf morphology and thermotolerance in rice (Oryza sativa L.).

Plant architecture and stress tolerance play important roles in rice breeding. Specific leaf morphologies and ideal plant architecture can effectively improve both abiotic stress resistance and rice grain yield. However, the mechanism by which plants simultaneously regulate leaf morphogenesis and stress resistance remains elusive. Here, we report that SRL10, which encodes a double-stranded RNA-binding protein, regulates leaf morphology and thermotolerance in rice through alteration of microRNA biogenesis. The srl10 mutant had a semi-rolled leaf phenotype and elevated sensitivity to high temperature. SRL10 directly interacted with catalase isozyme B (CATB), and the two proteins mutually increased one other's stability to enhance hydrogen peroxide (H2 O2 ) scavenging, thereby contributing to thermotolerance. The natural Hap3 (AGC) type of SRL10 allele was found to be present in the majority of aus rice accessions, and was identified as a thermotolerant allele under high temperature stress in both the field and the growth chamber. Moreover, the seed-setting rate was 3.19 times higher and grain yield per plant was 1.68 times higher in near-isogenic line (NIL) carrying Hap3 allele compared to plants carrying Hap1 allele under heat stress. Collectively, these results reveal a new locus of interest and define a novel SRL10-CATB based regulatory mechanism for developing cultivars with high temperature tolerance and stable yield. Furthermore, our findings provide a theoretical basis for simultaneous breeding for plant architecture and stress resistance.

Comparison of the efficacy of gossypol acetate enantiomers in rats with uterine leiomyoma.

Gossypol acetate (GA), as the product of racemic gossypol and acetic acid conjugated by hydrogen bond, is hydrolyzed into gossypol to exert its effect on treating uterine leiomyoma (UL), which has been listed in China. But hypokalemia and mild changes of liver function limit its clinical application. It had been reported that the biological activities of gossypol optical isomers were different. In this study, we aimed to clarify whether there were differences in the efficacy of gossypol enantiomers and whether a single gossypol optical isomer could alleviate adverse reactions in the treatment of UL. The results indicated that (-)-GA and (+)-GA had significant therapeutic effect on rats with UL. Interestingly, (-)-GA could better significantly ameliorate the pathological structure, inhibit the secretion of estrogen, and downregulate the expression of estrogen receptor-alpha (ER-α) and progesterone receptor (PR) than (+)-GA. Additionally, (-)-GA could better evidently decrease the symptoms of abnormally elevated inflammatory factors caused by UL. In contrast, (-)-GA and (+)-GA had certain effects on potassium ion concentration in serum, liver and kidney function, and the effects of (+)-GA on liver function were more obvious than (-)-GA. These findings will be of great significance to the drug development of gossypol optical isomers.

A lightweight segmentation network for endoscopic surgical instruments based on edge refinement and efficient self-attention.

In robot-assisted surgical systems, surgical instrument segmentation is a critical task that provides important information for surgeons to make informed decisions and ensure surgical safety. However, current mainstream models often lack precise segmentation edges and suffer from an excess of parameters, rendering their deployment challenging. To address these issues, this article proposes a lightweight semantic segmentation model based on edge refinement and efficient self-attention. The proposed model utilizes a lightweight densely connected network for feature extraction, which is able to extract high-quality semantic information with fewer parameters. The decoder combines a feature pyramid module with an efficient criss-cross self-attention module. This fusion integrates multi-scale data, strengthens focus on surgical instrument details, and enhances edge segmentation accuracy. To train and evaluate the proposed model, the authors developed a private dataset of endoscopic surgical instruments. It containing 1,406 images for training, 469 images for validation and 469 images for testing. The proposed model performs well on this dataset with only 466 K parameters, achieving a mean Intersection over Union (mIoU) of 97.11%. In addition, the model was trained on public datasets Kvasir-instrument and Endovis2017. Excellent results of 93.24% and 95.83% were achieved on the indicator mIoU, respectively. The superiority and effectiveness of the method are proved. Experimental results show that the proposed model has lower parameters and higher accuracy than other state-of-the-art models. The proposed model thus lays the foundation for further research in the field of surgical instrument segmentation.

Copper-Catalyzed Difluoroalkylation Reaction.

This review describes recent advances in copper-catalyzed difluoroalkylation reactions. The RCF2 radical is generally proposed in the mechanism of these reactions. At present, various types of copper-catalyzed difluoroalkylation reactions have been realized. According to their characteristics, we classify these difluoroalkylation reactions into three types.

Performance and methane potential of up-flow anaerobic sludge blanket treating thermal hydrolyzed sludge dewatering liquor.

Thermal hydrolysis pretreatment could release organic sufficiently from solid into liquid phase to accelerate the high solid sludge anaerobic digestion. Thus, up-flow anaerobic sludge blanket (UASB) could be a promising energy recovery process to treat thermal hydrolyzed sludge dewatering liquor with significantly augmented the organic loading rate (OLR). In this study, its performance was investigated using a lab-scale UASB to treat sludge dewatering liquor after 165 °C, 30 min thermal hydrolysis pretreatment. The results show that 85.57% of the organic in thermal hydrolyzed sludge dewatering liquor could be converted to methane. The UASB adapts to high OLR stably, and the COD removal efficiency was 71.98 ± 1.95% at OLR of 18.35 ± 0.78 kgCOD·(m3·d)-1, and the gap between the maximum potential and experimental methane production yields could be observed during different OLRs. It could be explained as the methanogenesis rate decreased due to the shift of dominant pathway from acetoclastic methanogenesis to syntrophic acetate oxidation following hydrogenotrophic methanogenesis. Methanospirillum became the dominant methanogen with the increase of OLR. In addition, the methane production yield and rate would be hindered till the ammonia nitrogen concentration exceeds 4 g·L-1. Direct interspecies electron transfer could be promising methods to improve UASB performance treating thermal hydrolyzed dewatering liquor.

Role of curcumin in the treatment of acute kidney injury: research challenges and opportunities.

BACKGROUND: Acute kidney injury (AKI) is a common complication in clinical inpatients, and it continues a high morbidity and mortality rate despite many clinical treatment measures. AKI is triggered by infections, surgery, heavy metal exposure and drug side effects, but current chemical drugs often fall short of expectations for AKI treatment and have toxic side effects. Therefore, finding new interventions and treatments, especially of natural origin, is of remarkable clinical significance and application. The herbal monomer curcumin is a natural phenolic compound extracted from the plant Curcuma longa and showed various biological activities, including AKI. Furthermore, recent studies have shown that curcumin restores renal function by modulating the immune system and the release of inflammatory mediators, scavenging oxygen free radicals, reducing apoptosis and improving mitochondrial dynamics. However, curcumin has a low bioavailability, which limits its clinical application. For this reason, it is essential to investigate the therapeutic effects and molecular mechanisms of curcumin in AKI, as well as to improve its bioavailability for curcumin formulation development and clinical application. PURPOSE: This review summarizes the sources, pharmacokinetics, and limitations in the clinical application of curcumin and explores methods to optimize its bioavailability using nanotechnology. In particular, the therapeutic effects and molecular mechanisms of curcumin on AKI are highlighted to provide a theoretical basis for AKI treatment in clinical practices. METHODS: This review was specifically searched by means of a search of three databases (Web of Science, PubMed and Science Direct), till December 2021. Search terms were "Curcumin", "Acute kidney injury", "AKI", " Pharmacokinetics", "Mitochondria" and "Nano formulations". The retrieved data followed PRISMA criteria (preferred reporting items for systematic review) RESULTS: Studies have shown that curcumin responded to AKI-induced renal injury and restored renal tubular epithelial cell function by affecting multiple signaling pathways in AKI models induced by factors such as cisplatin, lipopolysaccharide, ischemia/reperfusion, gentamicin and potassium dichromate. Curcumin was able to affect NF-κB signaling pathway and reduce the expression of IL-1ß, IL-6, IL-8 and TNF-α, thus preventing renal inflammatory injury. In the prevention of renal tubular oxidative damage, curcumin reduced ROS production by activating the activity of Nrf2, HO-1 and PGC-1α. In addition, curcumin restored mitochondrial homeostasis by upregulating OPA1 and downregulating DRP1 expression, while reducing apoptosis by inhibiting the caspase-3 apoptotic pathway. In addition, due to the low bioavailability and poor absorption of curcumin in vivo, curcumin nanoformulations including nanoparticles, liposomes, and polymeric micelles are formulated to improve the bioavailability. CONCLUSION: This review provides new ideas for the use of curcumin in the prevention and treatment of AKI by modulating the molecular targets of several different cellular signaling pathways.

Multi-Modal Optical Imaging and Combined Phototherapy of Nasopharyngeal Carcinoma Based on a Nanoplatform.

Nasopharyngeal carcinoma (NPC) is a common malignant tumor of the head and neck with a high incidence rate worldwide, especially in southern China. Phototheranostics in combination with nanoparticles is an integrated strategy for enabling simultaneous diagnosis, real-time monitoring, and administration of precision therapy for nasopharyngeal carcinoma (NPC). It has shown great potential in the field of cancer diagnosis and treatment owing to its unique noninvasive advantages. Many Chinese and international research teams have applied nano-targeted drugs to optical diagnosis and treatment technology to conduct multimodal imaging and collaborative treatment of NPC, which has become a hot research topic. In this review, we aimed to introduce the recent developments in phototheranostics of NPC based on a nanoplatform. This study aimed to elaborate on the applications of nanoplatform-based optical imaging strategies and treatment modalities, including fluorescence imaging, photoacoustic imaging, Raman spectroscopy imaging, photodynamic therapy, and photothermal therapy. This study is expected to provide a scientific basis for further research and development of NPC diagnosis and treatment.