Celastrol Regulates the Hsp90-NLRP3 Interaction to Alleviate Rheumatoid Arthritis.

Previous studies have verified that celastrol (Cel) protects against rheumatoid arthritis (RA) by inhibiting the NLRP3 inflammasome signaling pathway, but the molecular mechanism by which Cel regulates NLRP3 has not been clarified. This study explored the specific mechanisms of Cel in vitro and in vivo. A type II collagen-induced arthritis (CIA) mouse model was used to study the antiarthritic activity of Cel; analysis of paw swelling, determination of the arthritis score, and pathological examinations were performed. The antiproliferative and antimigratory effects of Cel on TNF-α induced fibroblast-like synoviocytes (FLSs) were tested. Proinflammatory factors were evaluated using enzyme-linked immunosorbent assay (ELISA). The expression of NF-κB/NLRP3 pathway components was determined by western blotting and immunofluorescence staining in vitro and in vivo. The putative binding sites between Cel and Hsp90 were predicted through molecular docking, and the binding interactions were determined using the Octet RED96 system and coimmunoprecipitation. Cel decreased arthritis severity and reduced TNF-α-induced FLSs migration and proliferation. Additionally, Cel inhibited NF-κB/NLRP3 signaling pathway activation, reactive oxygen species (ROS) production, and proinflammatory cytokine secretion. Furthermore, Cel interacted directly with Hsp90 and blocked the interaction between Hsp90 and NLRP3 in FLSs. Our findings revealed that Cel regulates NLRP3 inflammasome signaling pathways both in vivo and in vitro. These effects are induced through FLSs inhibition of the proliferation and migration by blocking the interaction between Hsp90 and NLRP3.

The Contributions of Thrombospondin-1 to Epilepsy Formation.

Epilepsy is a neural network disorder caused by uncontrolled neuronal hyperexcitability induced by an imbalance between excitatory and inhibitory networks. Abnormal synaptogenesis plays a vital role in the formation of overexcited networks. Recent evidence has confirmed that thrombospondin-1 (TSP-1), mainly secreted by astrocytes, is a critical cytokine that regulates synaptogenesis during epileptogenesis. Furthermore, numerous studies have reported that TSP-1 is also involved in other processes, such as angiogenesis, neuroinflammation, and regulation of Ca2+ homeostasis, which are closely associated with the occurrence and development of epilepsy. In this review, we summarize the potential contributions of TSP-1 to epilepsy development.

Tocilizumab attenuates choroidal neovascularization by regulating macrophage polarization through the IL-6R/STAT3/VEGF pathway.

Globally, age-related macular degeneration (AMD) is the leading cause of irreversible visual impairment. Up to 80% of severe vision loss is caused by AMD, which is characterized by the development of choroidal neovascularization (CNV). Uncertainty exists regarding the precise pathophysiological mechanisms of CNV. It has been suggested that the interleukin (IL) IL-6/IL-6R signaling pathway is crucial in the progression of CNV. Tocilizumab (TCZ), a monoclonal antibody, binds to soluble and membrane-bound IL-6R and competitively inhibits IL-6 downstream signaling. Previous research has demonstrated that TCZ promotes several roles related to inflammation and neovascularization. However, the effects of TCZ on CNV and the underlying mechanism are still unknown. This study found that TCZ administration decreased the area and leakage of CNV lesions in the mice model of laser-induced CNV. Additionally, results demonstrated that TCZ promotes the expression of iNOS, CCL-3, CCL-5, TNF-α and inhibits the expression of Arg-1, IL-10, YM-1 and CD206. Furthermore, TCZ treatment inhibited the signal transducer and activator of transcription (STAT) STAT3/vascular endothelial growth factor (VEGF) pathway, which was activated after CNV formation. Colivelin, a STAT3 agonist, reversed the inhibitory effects of TCZ on CNV formation and macrophage polarization. In a mouse model of laser-induced CNV, our findings demonstrated that TCZ attenuated CNV formation and inhibited the leakage of CNV lesions by regulating macrophage polarization via inhibiting the STAT3/VEGF axis. TCZ is the potential therapeutic strategy for CNV.

High sensitivity and ultra-low concentration range photoacoustic spectroscopy based on trapezoid compound ellipsoid resonant photoacoustic cell and partial least square.

A high sensitivity and ultra-low concentration range photoacoustic spectroscopy (PAS) gas detection system, which was based on a novel trapezoid compound ellipsoid resonant photoacoustic cell (TCER-PAC) and partial least square (PLS), was proposed to detect acetylene (C2H2) gas. In the concentration range of 0.5 ppm ∼ 10.0 ppm, the limit of detection (LOD) values of TCER-PAC-based PAS system without data processing was 66.4 ppb, which was lower than that of the traditional trapezoid compound cylindrical resonant photoacoustic cell (TCCR-PAC). The experimental results indicated that the TCER-PAC had higher sensitivity than of TCCR-PAC. Within the concentration range of 12.5 ppb ∼ 125.0 ppb, the LOD and limit of quantification (LOQ) of TCER-PAC-based PAS system combined with PLS regression algorithm were 1.1 ppb and 3.7 ppb, respectively. The results showed that higher detection sensitivity and lower LOD were obtained by PAS system with TCER-PAC and PLS than that of TCCR-PAC-based PAS system.

Low but highly geographically structured genomic diversity of East Asian Eurasian otters and its conservation implications.

Populations of Eurasian otters Lutra lutra, one of the most widely distributed apex predators in Eurasia, have been depleted mainly since the 1950s. However, a lack of information about their genomic diversity and how they are organized geographically in East Asia severely impedes our ability to monitor and conserve them in particular management units. Here, we re-sequenced and analyzed 20 otter genomes spanning continental East Asia, including a population at Kinmen, a small island off the Fujian coast, China. The otters form three genetic clusters (one of L. l. lutra in the north and two of L. l. chinensis in the south), which have diverged in the Holocene. These three clusters should be recognized as three conservation management units to monitor and manage independently. The heterozygosity of the East Asian otters is as low as that of the threatened carnivores sequenced. Historical effective population size trajectories inferred from genomic variations suggest that their low genomic diversity could be partially attributed to changes in the climate since the mid-Pleistocene and anthropogenic intervention since the Holocene. However, no evidence of genetic erosion, mutation load, or high level of inbreeding was detected in the presumably isolated Kinmen Island population. Any future in situ conservation efforts should consider this information for the conservation management units.

PD-1/PD-L1 inhibitors-associated cardiac adverse events: a retrospective and real-world study based on the FDA Adverse Event Reporting System (FAERS).

BACKGROUND: Programmed cell death protein-1 (PD-1) and programmed cell death ligand-1 (PD-L1) inhibitors have reformed the treatment landscape for various malignancies and improved prognosis of patients. However, they also lead to events that although rare may prove to be fatal. RESEARCH DESIGN AND METHODS: Data from July 2014 to June 2022 based on FDA Adverse Event Reporting System (FAERS) were analyzed. The signal index reporting odds ratio (ROR) was used to evaluate the correlation between cardiac AEs and given medications. The indications and the median time to onset (TTO) of different PD-1/PD-L1 inhibitors were compared. RESULTS: Cardiac AEs are rare but may be fatal with particular profiles in primary tumor, onset time, and especially gender. We identified 11,538 reports that were related to cardiotoxicity of PD-1/PD-L1 inhibitors, in which 178 different preferred terms (PTs) were distinguished, and nivolumab reported the most PTs with signal. All targeted medications showed signals in myocardial disorders and pericardial disorders, which tend to occur in the first 1-2 months. Non-small cell neoplasm was the top and common indication during anti-PD-1 or anti-PD-L1 therapy with cardiotoxicity. CONCLUSIONS: This study could help early diagnosis and surveillance of ICIs-related cardiotoxicity.

Photoacoustic Spectroscopy Gas Detection Technology Research Progress.

Photoacoustic spectroscopy (PAS) can be utilized as an ultrasensitive gas detection method. The basic principles of gas detection using PAS are discussed in this paper. First, the basic instrumentation for a PAS gas detection system is introduced focusing on the photoacoustic cell. The discussion includes non-resonant photoacoustic cells and the different types of resonant photoacoustic cells, including the longitudinal photoacoustic cell, the Helmholtz photoacoustic cell, the T-type photoacoustic cell, and the high-frequency resonant photoacoustic cell. The basic working principles of each of these, cells as well as the advantages and disadvantages of photoacoustic cells are discussed, and the development of newer types of photoacoustic cells in recent years is outlined in detail. This review provides detailed reference information and guidance for interested researchers who would like to design and build advanced photoacoustic cells for gas detection.

Inhibition of PTEN-induced kinase 1 autophosphorylation may assist in preventing epileptogenesis induced by pentylenetetrazol.

PTEN-induced kinase 1 (PINK1) autophosphorylation-triggered mitophagy is the main mitophagic pathway in the nervous system. Moreover, multiple studies have confirmed that mitophagy is closely related to the occurrence and development of epilepsy. Therefore, we speculated that the PINK1 autophosphorylation may be involved in epileptogenesis by mediating mitophagic pathway. This study aimed to explore the contribution of activated PINK1 to epileptogenesis induced by pentylenetetrazol (PTZ) in Sprague‒Dawley rats. During PTZ-induced epileptogenesis, the levels of phosphorylated PINK1 were increased, accompanied by elevated mitophagy, mitochondria oxidative stress and neuronal damage. After microRNA intervention targeting translocase outer mitochondrial membrane 7 (TOM7) or overlapping with the m-AAA protease 1 homolog (OMA1), the levels of PINK1 phosphorylation, mitophagy, mitochondrial oxidative stress, neuronal injury were observed in the rats with induced epileptogenesis. Furthermore, inhibiting of the expression of TOM7, a positive regulator of PINK1 autophosphorylation, reversed the increase in PINK1 phosphorylation and alleviated mitophagy, neuronal injury, thereby preventing epileptogenesis. In contrast, reducing the levels of OMA1, a negative regulator of PINK1 autophosphorylation, led to increased phosphorylation of PINK1, accompanied by aggravated neuronal injury and ultimately, epileptogenesis. This study confirmed the contribution of activated PINK1 to PTZ-induced epileptogenesis and suggested that the inhibition of PINK1 autophosphorylation may assist in preventing epileptogenesis.

Complete Genome Sequence and Pan-Genome Analysis of Shewanella oncorhynchi Z-P2, a Siderophore Putrebactin-Producing Bacterium.

In this study, we reported the complete genome sequence of Shewanella oncorhynchi for the first time. S. oncorhynchi Z-P2 is a bacterium that produces the siderophore putrebactin. Its genome consists of a circular chromosome of 5,034,612 bp with a G + C content of 45.4%. A total of 4544 protein-coding genes, 109 tRNAs and 31 rRNAs were annotated by the RAST. Five non-ribosomal peptide synthetase (NRPS) and polyketide synthetase (PKS) gene clusters were identified by the antiSMASH analysis. The pan-genome analysis of Z-P2 and 10 Shewanella putrefaciens revealed 9228 pan-gene clusters and 2681 core gene clusters, with Z-P2 having 618 unique gene clusters. Additionally, the gene cluster involved in putrebactin biosynthesis in Z-P2 was annotated, and the mechanism of putrebactin biosynthesis was analyzed. The putrebactin produced by Z-P2 was detected using UPLC-MS analysis, with an [M + H]+ molecular ion at m/z 373.21. These findings provide valuable support for further research on the genetic engineering of putrebactin biosynthetic genes of Z-P2 and their potential applications.

Neutrophil extracellular traps boost laser-induced mouse choroidal neovascularization through the activation of the choroidal endothelial cell TLR4/HIF-1α pathway.

Choroidal neovascularization (CNV) is characterized by the infiltration of immune cells, particularly neutrophils. Neutrophil extracellular trap (NET) facilitates the angiogenesis of pulmonary endothelial cells via activating Toll-like receptor 4 (TLR4). TLR4 promotes the expression of transcription factor hypoxia inducible factor-1α (HIF-1α), which promotes inflammation and angiogenesis via the up-regulation of metalloproteinase-9 (MMP-9) and interleukin-1ß (IL-1ß). In the present study, we aimed to identify the formation of NET and its role in CNV. Our results showed that NET levels were increased in a mouse laser-induced CNV model via oxidative stress, whereas the inhibition of NET alleviated CNV. In vitro, NET activated the TLR4/HIF-1α pathway in human choroidal endothelial cells (HCECs). Additionally, NET increased the transcription and expression of MMP-9 and IL-1ß in HCECs via activating the TLR4/HIF-1α pathway. Meanwhile, NET promoted the inflammatory response accompanied by the proliferation, migration and tube formation of HCECs in a MMP-9- and IL-1ß-dependent manner. In conclusion, NET was up-regulated in CNV and promoted the formation of CNV via activating the TLR4/HIF-1α pathway in choroidal endothelial cells. Our data uncovered the novel role of NET in promoting the formation of CNV. The underlying mechanism of NET could be targeted to delay the process of CNV.

High-precision prediction of blood glucose concentration utilizing Fourier transform Raman spectroscopy and an ensemble machine learning algorithm.

Raman spectroscopy has gained popularity in analyzing blood glucose levels due to its non-invasive identification and minimal interference from water. However, the challenge lies in how to accurately predict blood glucose concentrations in human blood using Raman spectroscopy. This paper researches a novel integrated machine learning algorithm called Bagging-ABC-ELM. The optimal input weights and biases of extreme learning machine (ELM) model are obtained by artificial bee colony (ABC) algorithm. The bagging algorithm is used to obtain a better the stability of the model and higher performance than ELM algorithm. The results show that the mean value of coefficient of determination is 0.9928, and root mean square error is 0.1928. Compared to other regression models, the Bagging-ABC-ELM model exhibited superior prediction accuracy, robustness, and generalization capability. The Bagging-ABC-ELM model presents a promising alternative for analyzing blood glucose levels in clinical and research settings.

[Herbal-moxa plaster for diarrhea type irritable bowel syndrome of spleen and kidney yang deficiency: a randomized controlled trial].

OBJECTIVE: To compare the clinical efficacy between herbal-moxa plaster and moxa-box moxibustion for diarrhea type irritable bowel syndrome (IBS-D) of spleen and kidney yang deficiency. METHODS: Eighty patients with IBS-D of spleen and kidney yang deficiency were randomly divided into a herbal-moxa plaster group and a moxa-box moxibustion group, 40 cases in each group. The patients in the two groups were treated with conventional acupuncture at Baihui (GV 20), Yintang (GV 24+), Zhongwan (CV 12) and bilateral Tianshu (ST 25), Yinlingquan (SP 9), and Taixi (KI 3), etc. In addition, the patients in the herbal-moxa plaster group were treated with herbal-moxa plaster (Wenyang Fuzheng ointment, composed of prepared monkshood, prepared evodia rutaecarpa, dried ginger, cinnamon, etc.) at Shenque (CV 8), Guanyuan (CV 4), Zhongwan (CV 12) and bilateral Tianshu (ST 25), Shenshu (BL 23) and Shangjuxu (ST 37); the patients in the moxa-box moxibustion group were treated with moxa-box moxibustion at the same acupoints as the herbal-moxa plaster group. The acupuncture-moxibustion treatment was provided once every other day for 4 weeks (14 treatments). Before and after treatment, the scores of clinical symptom of TCM, irritable bowel syndrome (IBS) symptom severity scale (IBS-SSS) and IBS quality of life scale (IBS-QOL) were compared between the two groups, and the clinical efficacy was evaluated. RESULTS: Compared with those before treatment, each item scores and total scores of clinical symptom of TCM, and IBS-SSS scores in the two groups were reduced after treatment (P<0.05). The abdominal bloating score, stool frequency score and total score of clinical symptom of TCM as well as IBS-SSS score in the herbal-moxa plaster group were lower than those in the moxa-box moxibustion group (P<0.05). Compared with those before treatment, the IBS-QOL scores in the two groups were increased after treatment (P<0.05), and the IBS-QOL score in the herbal-moxa plaster group was higher than that in the moxa-box moxibustion group (P<0.05). The total effective rate was 92.5% (37/40) in the herbal-moxa plaster group, which was higher than 85.0% (34/40) in the moxa-box moxibustion group (P<0.05). CONCLUSION: On the basis of conventional acupuncture treatment, herbal-moxa plaster could effectively improve the clinical symptoms and quality of life in IBS-D patients of spleen and kidney yang deficiency, and its efficacy is superior to that of moxa-box moxibustion.

The Paeonia qiui R2R3-MYB Transcription Factor PqMYBF1 Positively Regulates Flavonol Accumulation.

Tree peony is a "spring colored-leaf" plant which has red leaves in early spring, and the red color of the leaves usually fades in late spring. Flavonols are one subgroup of flavonoids, and they affect the plant organs' color as co-pigments of anthocyanins. To investigate the color variation mechanism of leaves in tree peony, PqMYBF1, one flavonol biosynthesis-related MYB gene was isolated from Paeonia qiui and characterized. PqMYBF1 contained the SG7 and SG7-2 motifs which are unique in flavonol-specific MYB regulators. Subcellular localization and transactivation assay showed that PqMYBF1 localized to the nucleus and acted as a transcriptional activator. The ectopic expression of PqMYBF1 in transgenic tobacco caused an observable increase in flavonol level and the anthocyanin accumulation was decreased significantly, resulting in pale pink flowers. Dual-luciferase reporter assays showed that PqMYBF1 could activate the promoters of PqCHS, PqF3H, and PqFLS. These results suggested that PqMYBF1 could promote flavonol biosynthesis by activating PqCHS, PqF3H, and PqFLS expression, which leads metabolic flux from anthocyanin to flavonol pathway, resulting in more flavonol accumulation. These findings provide a new train of thought for the molecular mechanism of leaf color variation in tree peony in spring, which will be helpful for the molecular breeding of tree peony with colored foliage.

Fluoropolymer-MOF Hybrids with Switchable Hydrophilicity for 19F MRI-Monitored Cancer Therapy.

Cancer theranostics that combines cancer diagnosis and therapy is a promising approach for personalized cancer treatment. However, current theranostic strategies suffer from low imaging sensitivity for visualization and an inability to target the diseased tissue site with high specificity, thus hindering their translation to the clinic. In this study, we have developed a tumor microenvironment-responsive hybrid theranostic agent by grafting water-soluble, low-fouling fluoropolymers to pH-responsive zeolitic imidazolate framework-8 (ZIF-8) nanoparticles by surface-initiated RAFT polymerization. The conjugation of the fluoropolymers to ZIF-8 nanoparticles not only allows sensitive in vivo visualization of the nanoparticles by 19F MRI but also significantly prolongs their circulation time in the bloodstream, resulting in improved delivery efficiency to tumor tissue. The ZIF-8-fluoropolymer nanoparticles can respond to the acidic tumor microenvironment, leading to progressive degradation of the nanoparticles and release of zinc ions as well as encapsulated anticancer drugs. The zinc ions released from the ZIF-8 can further coordinate to the fluoropolymers to switch the hydrophilicity and reverse the surface charge of the nanoparticles. This transition in hydrophilicity and surface charge of the polymeric coating can reduce the "stealth-like" nature of the agent and enhance specific uptake by cancer cells. Hence, these hybrid nanoparticles represent intelligent theranostics with highly sensitive imaging capability, significantly prolonged blood circulation time, greatly improved accumulation within the tumor tissue, and enhanced anticancer therapeutic efficiency.

Unsupervised model adaptation for multivariate calibration by domain adaptation-regularization based kernel partial least square.

In chemometrics, calibration model adaptation is desired when training- and test-samples come from different distributions. Domain-invariant feature representation is currently a successful strategy to realize model adaptation and has received wide attention. The paper presents a nonlinear unsupervised model adaptation method termed as domain adaption regularization-based kernel partial least squares regression (DarKPLS). DarKPLS aims to minimize the source and target distributions in a low-dimensional latent space projected from the reproducing kernel Hilbert space (RKHS) generated with the labeled source data and unlabeled target data. Specially, the distributional means and variances between source and target latent variables are aligned in the RKHS. By extending existing domain invariant partial least square regression (di-PLS) with the projected maximum mean discrepancy (PMMD) to reduce the mean discrepancy in the RKHS further, DarKPLS could realize fine-grained domain alignment that further improves the adaptation performance. DarKPLS is applied to the γ-polyglutamic acid fermentation dataset, tobacco dataset and corn dataset, and it demonstrates improved prediction results in comparison with No adaptation partial least squares (PLS), null augmented regression (NAR), extended linear joint trained framework (ExtJT), scatter component analysis (SCA) and domain-invariant iterative partial least squares (DIPALS).

An extreme learning machine optimized by differential evolution and artificial bee colony for predicting the concentration of whole blood with Fourier Transform Raman spectroscopy.

Raman spectroscopy, with its advantages of non-contact nature, rapid detection, and minimum water interference, is promising for non-invasive blood detection or diagnosis in clinic applications. However, there is a critical issue that how to accurately analyze blood composition by Raman spectroscopy. In this study, we apply extreme learning machine (ELM) algorithm and a multivariate calibration regression model to analyze the results from Raman spectroscopy and determine the component's concentrations in blood samples, including glucose, cholesterol, and triglyceride. Self-adaption differential evolution artificial bee colony (SADEABC) algorithm was further applied to increase the data's accuracy and robustness. The obtained data for coefficient of determination, root mean square error of calibration, root mean square error of prediction, and relative percent deviation, were 0.9822, 0.3993, 0.3827, and 6.6679 for glucose, 0.9786, 0.2104, 0.2088 and 5.9533 for cholesterol, and 0.9921, 0.2744, 0.3433 and 10.5075 for triglyceride, respectively. Results demonstrated that the model based on SADEABC-ELM show much better prediction data than those models based on the ELM and ABC-ELM.

Autologous platelet-rich gel in the treatment of diabetic foot ulcers: A retrospective study.

This study retrospectively investigated the effectiveness and safety of autologous platelet-rich gel (APRG) for the treatment of diabetic foot ulcers (DFU). In this retrospective study, we reviewed the electronic medical records (EMR) of 72 patients with DFU. The patients were allocated to a treatment group (n = 36) or a control group (n = 36). The patients in both groups received standard care (SC) and dressing change. In addition, patients in the treatment group also received APRG. Patients in both groups were treated for 12 weeks. The outcomes were DFU healing time (days), length of hospital stay (days), healing rate of DFU, DFU surface area reduction (cm2), and adverse events. We assessed and analyzed the outcomes before and after the 12-week treatment period. After treatment, there were significant differences in DFU healing time (P = .04), length of hospital stay (P = .04), DFU healing rate, and DFU surface area reduction (P < .01). Regarding safety, no EMR reported adverse events in this study. The results of this study showed that the APRG may benefit patients with DFU. However, high-quality prospective randomized controlled trials are required to verify these findings.

Celastrol inhibits rheumatoid arthritis by inducing autophagy via inhibition of the PI3K/AKT/mTOR signaling pathway.

OBJECTIVE: Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disorder of the synovial joints. Celastrol (Cel) is a quinone-methylated triterpenoid extracted from Tripterygium wilfordii Hook F (TwHF) that has been proven to be effective in treating RA. However, the underlying molecular mechanism of celastrol in the treatment of RA remains unknown. This study explored the protective effect of celastrol against RA and the specific mechanisms of celastrol in vitro and in vivo. METHODS: A chicken type II collagen (CII)-induced arthritis (CIA) mouse model was used to explore the anti-arthritic effects of celastrol, and paw swelling degree, the poly-arthritis index score and serum cytokine levels were determined. Pathological morphology was observed using hematoxylin and eosin (H&E) staining. The influences of celastrol on the proliferation of tumor necrosis factor-α (TNF-α)-induced fibroblast-like synoviocytes (FLSs) were tested by Cell Counting Kit-8 (CCK-8) assays and5-ethynyl-2'-deoxyuridine (EdU) staining assays. The level of autophagy was detected by transmission electron microscopy (TEM). Furthermore, the PI3K/AKT/mTOR pathway and the status of autophagy in the CIA model and FLSs were also detected by western blot and immunofluorescence staining. RESULTS: The results showed that celastrol decreased arthritis severity and inhibited TNF-α-induced FLSs proliferation. Additionally, celastrol decreased the secretion of pro-inflammatory cytokines. Moreover, celastrol increased autophagosome levels and LC3B protein expression in TNF-α-treated FLSs. Furthermore, celastrol increased the protein expression of LC3-II and Beclin-1 and decreased the phosphorylation degree of mTOR and AKT. CONCLUSION: In conclusion, our findings confirmed that celastrol ameliorates RA via the up-regulation of autophagy by inhibiting the PI3K/AKT/mTOR axis.

Low-Fouling Gold Nanorod Theranostic Agents Enabled by a Sulfoxide Polymer Coating.

Gold nanorods (GNRs) are widely used in various biomedical applications such as disease imaging and therapy due to their unique plasmonic properties. To improve their bioavailability, GNRs often need to be coated with hydrophilic polymers so as to impart stealth properties. Poly(ethylene glycol) (PEG) has been long used as such a coating material for GNRs. However, there is increasing acknowledgement that the amphiphilic nature of PEG facilitates its interaction with protein molecules, leading to immune recognition and consequent side effects. This has motivated the search for new classes of low-fouling polymers with high hydrophilicity as alternative low-fouling surface coating materials for GNRs. Herein, we report the synthesis, characterization, and application of GNRs coated with highly hydrophilic sulfoxide-containing polymers. We investigated the effect of the sulfoxide polymer coating on the cellular uptake and in vivo circulation time of the GNRs and compared these properties with pegylated GNR counterparts. The photothermal effect and photoacoustic imaging of these polymer-coated GNRs were also explored, and the results show that these GNRs are promising as nanotheranostic particles for the treatment of cancer.

Chrysin alleviates lipopolysaccharide-induced neuron damage and behavioral deficits in mice through inhibition of Fyn.

Fyn, a non-receptor tyrosine kinase, plays an important role in microglial-mediated neuroinflammation and may serve as a candidate therapeutic target for neuropsychiatric diseases. In this study, we discovered that chrysin, a natural flavonoid compound, suppressed the activation of Fyn kinase and further alleviated neuroinflammation-induced neuron damage and behavior deficits. Functionally, chrysin improved lipopolysaccharide (LPS)-induced memory impairment and depressive behaviors in mice, it also protected against LPS-induced neuronal degeneration and loss and synaptic defects in mice. Our study demonstrated that chrysin inhibited the activation of microglia and reduced the expression of NLRP3 and IL-1ß. Furthermore, our data indicated that chrysin blocked phosphorylation of Fyn and activation of NF-κB. Transfection with siRNA-Fyn validated that knockdown of Fyn partly abolished the inhibitory effect of chrysin on the expression of the NLRP3 inflammasome and NF-κB activation. Taken together, our findings revealed that chrysin alleviated LPS-induced neuron damage and behavioral deficits by inhibiting the expression of the NLRP3 inflammasome and NF-κB pathway, which might be mediated by inhibition of Fyn.