Quantum Mechanical-Based Stability Evaluation of Crystal Structures for HIV-Targeted Drug Cabotegravir.

The long-acting parenteral formulation of the HIV integrase inhibitor cabotegravir (GSK744) is currently being developed to prevent HIV infections, benefiting from infrequent dosing and high efficacy. The crystal structure can affect the bioavailability and efficacy of cabotegravir. However, the stability determination of crystal structures of GSK744 have remained a challenge. Here, we introduced an ab initio protocol to determine the stability of the crystal structures of pharmaceutical molecules, which were obtained from crystal structure prediction process starting from the molecular diagram. Using GSK744 as a case study, the ab initio predicted that Gibbs free energy provides reliable further refinement of the predicted crystal structures and presents its capability for becoming a crystal stability determination approach in the future. The proposed work can assist in the comprehensive screening of pharmaceutical design and can provide structural predictions and stability evaluation for pharmaceutical crystals.

Optimization, purification, and characterization of hydroxylamine oxidoreductase from Acinetobacter sp. Y1.

Hydroxylamine oxidoreductase (HAO) is a key enzyme involved in ammonium removal pathway. To further study the enzyme, HAO was purified from heterotrophic nitrifier Acinetobacter sp. Y1 and its property was investigated. Results of single-factor experiments showed that the optimal carbon source, nitrogen source, and C/N ratio were trisodium citrate, ammonium sulfate, and 14, respectively, with incubation time of 16 H. DEAE SefinoseTM FF anion-exchange chromatography was used to purify HAO, followed by SefinoseTM CL-6B gel filtration chromatography. SDS-PAGE revealed that a 47 kDa enzyme was purified successfully, with a purification fold of 7.32 and a recovery rate of 19.40%. The optimized enzyme activity of purified HAO was tested at pH 8.0 and 30 °C. The results showed that the activity was increased by 43.78% and 25.64% in the presence of 1 mM Fe2+ and Fe3+ , respectively. HAO activity was increased with the increase of Na+ and K+ , Mn2+ , Zn2+ , Cu2+ , Ca2+ , Ba2+ inhibited the HAO activity at three concentrations. In addition, HAO activity was activated by ethylenediaminetetraacetic acid at 0.4 mM, and a negative effect arose as the dose increased. The purified enzyme from Y1 is different from other reported HAOs. Further study should be conducted to investigate the enzyme.

Nanoassembly of probucol enables novel therapeutic efficacy in the suppression of lung metastasis of breast cancer.

Metastasis is one of the major obstacles hindering the success of cancer therapy. The directed nanoassembly of probucol results in the "DNP" system, which greatly improves the oral delivery of probucol and subsequently leads to a novel therapeutic efficacy of probucol in the suppression of lung metastasis of breast cancer. DNP is formed by employing the intermolecular hydrophobic interactions between probucol and polyethylene glycol p-(1,1,3,3-tetramethylbutyl)-phenyl ether (also known as Triton X-100). After oral administration, the probucol concentration in the intestines is surprisingly about 200 times higher if it is applied as DNP rather than free probucol; it can be absorbed into intestinal enterocytes via clathrin-mediated endocytosis and transported into the systemic circulation through the lymphatic pathway. Moreover, the oral bioavailability of probucol is significantly higher-13.55 times higher-when applied as DNP in place of free probucol. The drug concentration in major organs is also significantly increased. The in vitro measurements show that the migration and invasion abilities of 4T1 cells are obviously inhibited by DNP. In particular, in an orthotopic metastatic breast cancer model, the notable suppression of lung metastasis from DNP is observed, but no effect is seen from the free-probucol suspension. As a result, the directed drug nanoassembly may open a new route for enhancing oral drug delivery and enable new therapeutic abilities for probucol against cancer metastasis.

Directed self-assembled nanoparticles of probucol improve oral delivery: fabrication, performance and correlation.

PURPOSE: We are reporting on the development of a unique drug delivery platform by directed self-assembly technique to improve the oral delivery of hydrophobic drugs. METHODS: Herein, a series of probucol directed self-assembled nanoparticles (PDN) were developed with two components of probucol and surfactant such as Tween 20, Tween 80, D-alpha-tocopheryl polyethylene glycol 1,000 succinate (TPGS) and HS-15, which was respectively named as T20-PDN, T80-PDN, TP-PDN and HS-PDN. The formation of various PDNs was determined by in vitro characterization and the physicochemical properties of these PDNs were determined. Moreover, the performance of PDN in enhancing the oral delivery and possible correlation between the in vitro properties and in vivo performances were investigated. RESULTS: PDN was homogenous nanometer-sized particles with negative surface charge. The cellular uptake of probucol in Caco-2 cell monolayer was respectively increased 1.15, 1.82, 1.59 and 5.31-fold by these PDN. In particular, the oral bioavailability of these PDN was significantly improved 3.0, 4.1, 5.4 and 10.4 folds compared with the free drug suspension. The enhanced cellular uptake and oral bioavailability were correlated with the characters of involved surfactants and the particle size of PDN. CONCLUSIONS: Thereby, the directed self-assembled nanoparticles could provide a new strategy for enhancing the oral delivery of hydrophobic drugs.

NEAT1 Promotes Valproic Acid-Induced Autism Spectrum Disorder by Recruiting YY1 to Regulate UBE3A Transcription.

Evidence suggests that long non-coding RNAs (lncRNAs) play a significant role in autism. Herein, we explored the functional role and possible molecular mechanisms of NEAT1 in valproic acid (VPA)-induced autism spectrum disorder (ASD). A VPA-induced ASD rat model was constructed, and a series of behavioral tests were performed to examine motor coordination and learning-memory abilities. qRT-PCR and western blot assays were used to evaluate target gene expression levels. Loss-and-gain-of-function assays were conducted to explore the functional role of NEAT1 in ASD development. Furthermore, a combination of mechanistic experiments and bioinformatic tools was used to assess the relationship and regulatory role of the NEAT1-YY1-UBE3A axis in ASD cellular processes. Results showed that VPA exposure induced autism-like developmental delays and behavioral abnormalities in the VPA-induced ASD rat model. We found that NEAT1 was elevated in rat hippocampal tissues after VPA exposure. NEAT1 promoted VPA-induced autism-like behaviors and mitigated apoptosis, oxidative stress, and inflammation in VPA-induced ASD rats. Notably, NEAT1 knockdown improved autism-related behaviors and ameliorated hippocampal neuronal damage. Mechanistically, it was observed that NEAT1 recruited the transcription factor YY1 to regulate UBE3A expression. Additionally, in vitro experiments further confirmed that NEAT1 knockdown mitigated hippocampal neuronal damage, oxidative stress, and inflammation through the YY1/UBE3A axis. In conclusion, our study demonstrates that NEAT1 is highly expressed in ASD, and its inhibition prominently suppresses hippocampal neuronal injury and oxidative stress through the YY1/UBE3A axis, thereby alleviating ASD development. This provides a new direction for ASD-targeted therapy.

The function of sphingolipids in different pathogenesis of Alzheimer's disease: A comprehensive review.

Sphingolipids (SPLs) represent a highly diverse and structurally complex lipid class. The discussion of SPL metabolism-related issues is of importance in understanding the neuropathological progression of Alzheimer's disease (AD). AD is characterized by the accumulation of extracellular deposits of the amyloid ß-peptide (Aß) and intraneuronal aggregates of the microtubule-associated protein tau. Critical roles of Aß oligomer deposited and ganglioside GM1 could be formed as "seed" from insoluble GAß polymer in initiating the pathogenic process, while tau might also mediate SPLs and their toxicity. The interaction between ceramide and α-Synuclein (α-Syn) accelerates the aggregation of ferroptosis and exacerbates the pathogenesis of AD. For instance, reducing the levels of SPLs can mitigate α-Syn accumulation and inhibit AD progression. Meanwhile, loss of SPLs may inhibit the expression of APOE4 and confer protection against AD, while the loss of APOE4 expression also disrupts SPLs homeostasis. Moreover, the heightened activation of sphingomyelinase promotes the ferroptosis signaling pathway, leading to exacerbated AD symptoms. Ferroptosis plays a vital role in the pathological progression of AD by influencing Aß, tau, APOE, and α-Syn. Conversely, the development of AD also exacerbates the manifestation of ferroptosis and SPLs. We are compiling the emerging techniques (Derivatization and IM-MS) of sphingolipidomics, to overcome the challenges of AD diagnosis and treatment. In this review, we examined the intricate neuro-mechanistic interactions between SPLs and Aß, tau, α-Syn, APOE, and ferroptosis, mediating the onset of AD. Furthermore, our findings highlight the potential of targeting SPLs as underexplored avenue for devising innovative therapeutic strategies against AD.

Reversal of multidrug resistance by mitochondrial targeted self-assembled nanocarrier based on stearylamine.

Multidrug resistance (MDR) remains one of the major challenges for successful chemotherapy. Herein, we tried to develope a mitochondria targeted teniposide loaded self-assembled nanocarrier based on stearylamine (SA-TSN) to reverse MDR of breast cancer. SA-TSN was nanometer-sized spherical particles (31.59 ± 3.43 nm) with a high encapsulation efficiency (99.25 ± 0.21%). The MDR in MCF-7/ADR cells was obviously reduced by SA-TSN, which mainly attributed to the markedly reduced expression of P-gp, increased percentages in G2 phase, selectively accumulation in mitochondria, decrease of mitochondrial membrane potential, and greatly improved apoptosis. The plasma concentration of teniposide was greatly improved by SA-TSN, and the intravenously administered SA-TSN could accumulate in the tumor site and penetrate into the inner site of tumor in MCF-7/ADR induced xenografts. In particular, the in vivo tumor inhibitory efficacy of SA-TSN in MCF-7/ADR induced models was more effective than that of teniposide loaded self-assembled nanocarrier without stearylamine (TSN) and teniposide solution (TS), which verified the effectiveness of SA-TSN in reversal of MDR. Thereby, SA-TSN has potential to circumvent the MDR for the chemotherapy of breast cancer.

IR780-doped cobalt ferrite nanoparticles@poly(ethylene glycol) microgels as dual-enzyme immobilized micro-systems: Preparations, photothermal-responsive dual-enzyme release, and highly efficient recycling.

To solve the problems of separating dual enzymes from the carriers of dual-enzyme immobilized micro-systems and greatly increase the carriers' recycling times, photothermal-responsive micro-systems of IR780-doped cobalt ferrite nanoparticles@poly(ethylene glycol) microgels (CFNPs-IR780@MGs) are prepared. A novel two-step recycling strategy is proposed based on the CFNPs-IR780@MGs. First, the dual enzymes and the carriers are separated from the reaction system as a whole via magnetic separation. Second, the dual enzymes and the carriers are separated through photothermal-responsive dual-enzyme release so that the carriers can be reused. Results show that CFNPs-IR780@MGs is 281.4 ± 9.6 nm with a shell of 58.2 nm, and the low critical solution temperature is 42 °C, and the photothermal conversion efficiency increases from 14.04% to 58.41% by doping 1.6% of IR780 into the CFNPs-IR780 clusters. The dual-enzyme immobilized micro-systems and the carriers are recycled 12 and 72 times, respectively, and the enzyme activity remains above 70%. The micro-systems can realize whole recycling of the dual enzymes and carriers and further recycling of the carriers, thus providing a simple and convenient recycling method for dual-enzyme immobilized micro-systems. The findings reveal the micro-systems' important application potential in biological detection and industrial production.

Dysregulated Gln-Glu-α-ketoglutarate axis impairs maternal decidualization and increases the risk of recurrent spontaneous miscarriage.

Recurrent spontaneous miscarriage (RSM) affects 1%-2% of fertile women worldwide and poses a risk of future pregnancy complications. Increasing evidence has indicated that defective endometrial stromal decidualization is a potential cause of RSM. Here, we perform liquid chromatography with mass spectrometry (LC-MS)-based metabolite profiling in human endometrial stromal cells (ESCs) and differentiated ESCs (DESCs) and find that accumulated α-ketoglutarate (αKG) derived from activated glutaminolysis contributes to maternal decidualization. Contrarily, ESCs obtained from patients with RSM show glutaminolysis blockade and aberrant decidualization. We further find that enhanced Gln-Glu-αKG flux decreases histone methylation and supports ATP production during decidualization. In vivo, feeding mice a Glu-free diet leads to a reduction of αKG, impaired decidualization, and an increase of fetal loss rate. Isotopic tracing approaches demonstrate Gln-dependent oxidative metabolism as a prevalent direction during decidualization. Our results demonstrate an essential prerequisite of Gln-Glu-αKG flux to regulate maternal decidualization, suggesting αKG supplementation as a putative strategy to rectify deficient decidualization in patients with RSM.

[Alternative Splicing Analysis of LACTB Gene and Expression Characteristics of Different Transcripts in Leukemia Cell Lines].

OBJECTIVE: To detect the expression of different transcripts of lactamase ß（LACTB) gene in leukemic cell lines. METHODS: NCBI website and DNAstar software were used to detect the Bioinformatics analysis of LACTB. The expression of different transcripts of LACTB gene in leukemic cell lines (THP-1, HL60, K562, U937, Jurkat and Raji) was detected by reverse transcription PCR (RT-PCR), DNA and clone sequencing; the expression of different transcripts of LACTB gene in leukemic cell lines was detected by Quantitative Real-time PCR. RESULTS: There were a variety of splicing isomers in LACTB, and it could produce a variety of protein isomers with conserved N-terminal and different C-terminal, moreover, there were many splice isoforms of LACTB in leukemia cell lines, and there were different expression patterns in different cell lines, including XR1, V1, V2 and V3. The expression of total LACTB showed high in HL60 cells, while low in Raji cells, and the difference was statistically significant (P<0.05). The V1 was high expression in U937 cells but low in Raji cells, and the difference was statistically significant (P<0.05). V2 was high expression in HL60 cells but lowly in Raji cells, and the difference was statistically significant (P<0.05). The expression of V3 was low in THP-1 cells, which was significantly different as compared with that in normal bone marrow (P<0.05). CONCLUSION: The reaserch found that there are many splice isomers of LACTB in leukemic cell lines, and there are different expression patterns in different cell lines.

LACTB and LC3 could serve as potential biomarkers of gastric cancer to neoadjuvant chemotherapy with oxaliplatin plus S-1.

The present study investigated and evaluated the correlation between the expression of LACTB and LC3 and the clinical outcomes of patients with advanced gastric cancer treated with oxaliplatin plus S-1 neoadjuvant chemotherapy (NACT). A total of 51 patients with advanced gastric cancer underwent NACT treatment between June 2015 and June 2017. Pathomorphological changes in gastric cancer were analyzed by H&E staining. The expression level and subcellular localization of LACTB and LC3 in paraffin-embedded biopsies were detected by immunohistochemistry and immunofluorescence. The mRNA and protein expression of LACTB were investigated by reverse transcription quantitative polymerase chain reaction and Western blotting, respectively. Statistical analysis was performed to determine the association between the expression of LACTB and LC3 and clinical chemotherapy efficacy of NACT for gastric cancer. Among the 51 patients, 3 (5.88%), 27 (52.94%), 13 (25.49%) and 8 (15.69%) displayed complete remission, partial remission, stable disease and progressive disease, respectively. The rate of decreased LACTB expression was 68.6%, while the rate of increased LC3 expression was 60.8%. Furthermore, there was a significant negative correlation between the expression of LACTB and that of LC3 following NACT (P<0.001). High expression of LC3 (P<0.01) and low expression of LACTB (P<0.01) were associated with a poor response of patients with advanced gastric cancer to NACT. In conclusion, the expression of LACTB and LC3 may serve as a promising novel biomarker for determining the prognosis of patients with advanced gastric cancer receiving NACT, while its potential clinical significance requires further elucidation.

LACTB induced apoptosis of oxaliplatin-resistant gastric cancer through regulating autophagy-mediated mitochondrial apoptosis pathway.

Oxaliplatin (OXA), as a third-generation platinum anticancer drug, is a treatment drug for gastric cancer (GC). However, OXA resistance has become the main reason for OXA treatment failure. Serine beta-lactamase-like protein (LACTB), acts as a mitochondrial protein, can affect multiple cancer processes. Here, we aimed to investigate the function and mechanism of LACTB in OXA-resistant GC. After LACTB overexpression or autophagy activator (RAPA) treatment, cell proliferation, reactive oxygen species (ROS), apoptosis, mitochondrial dysfunction were evaluated through CCK-8 assay, Edu staining, flow cytometry and immunofluorescence assay. Moreover, DNA double-stranded damage and autophagy-related proteins were examined via western blot. We revealed that LACTB was downregulated in OXA-resistant MGC-803 cells, and overexpression of LACTB reduced the resistance of GC cells to OXA. Besides, our results uncovered that overexpression of LACTB induced apoptosis, reduced the mitochondrial membrane potential (MMP) and accelerated ROS accumulation in OXA-resistant MGC-803 (MGC-803/OXA) cells. Meanwhile, we verified that overexpression of LACTB decreased glucose uptake and ATP synthesis, induced mitochondria and DNA damages, and inhibited autophagy of MGC-803/OXA cells. Furthermore, our results certified that RAPA could weaken the function of LACTB on apoptosis and mitochondrial morphology and function in OXA-resistant MGC-803 cells with OXA treatment. Therefore, we demonstrated that LACTB could attenuate the resistance of MGC-803/OXA cells to OXA through autophagy-mediated mitochondrial morphological changes, mitochondrial dysfunction, and apoptosis, suggesting that LACTB, functions as a suppressor, is conducive to the therapy of OXA-resistant GC.

Ultrathin surface coated water-soluble cobalt ferrite nanoparticles with high magnetic heating efficiency and rapid in vivo clearance.

To obtain magnetic nanoparticles with high magnetic heating efficiency and rapid in vivo clearance, this study utilized an improved linear response theory model to theoretically simulate the specific absorption rate (SAR) value versus the particle size of cobalt ferrite nanoparticles (CFNPs). An accurate SAR curve consistent with experimental results was obtained using cubes instead of spheres as the shape of CFNPs, given that cube was closer to the actual shape of prepared CFNPs. Under the guidance of simulation, we predicted and prepared water-soluble cubic CFNPs of 10-13 nm in size, with an ultrathin surface coating less than 1 nm in thickness. These CFNPs were experimentally verified to have high magnetic heating efficiency and rapid in vivo clearance rate. Our CFNPs of 11.8 nm in size had a high intrinsic loss power of 12.11 nHm2/kg. Most of the cells were killed within 30 min under magnetic heating with CFNPs. In an in vivo study, these CFNPs can heat a tumor area to 45 °C (ΔT > 9 °C) within 120 s under a weak alternating magnetic field (27 kA/m, 115 kHz). Notably, these CFNPs had significant tumor inhibition rate in vivo and can be cleared from the body by more than 64% within 2 weeks, demonstrating excellent rapid in vivo clearance. This result was close to the clearance level of the magnetic resonance imaging contrast agent Feridex. Therefore, our CFNPs had high magnetic heating efficiency and rapid in vivo clearance rate, indicating their great potential for future clinical applications.

Highly Penetrable and On-Demand Oxygen Release with Tumor Activity Composite Nanosystem for Photothermal/Photodynamic Synergetic Therapy.

A deep penetrating and pH-responsive composite nanosystem was strategically developed to improve the efficacy of synergetic photothermal/photodynamic therapy (PTT/PDT) against hypoxic tumor. The designed nanosystem ([PHC]PP@HA NPs) was constructed by coloading hemoglobin (Hb) and chlorin e6 on polydopamine to build small-sized PHC NPs, which were encapsulated inside the polymer micelles (poly(ethylene glycol)-poly(ethylenimine)) and then capped with functionalized hyaluronic acid. The pH-responsive feature made [PHC]PP@HA NPs retain an initial size of ∼140 nm in blood circulation but rapidly release small PHC NPs (∼10 nm) with a high tumor-penetrating ability in the tumor microenvironment. The in vitro penetration experiment showed that the penetration depth of PHC NPs in the multicellular tumor spheroids exceeded 110 µm. The [PHC]PP@HA NPs exhibited excellent biocompatibility, deep tumor permeability, high photothermal conversion efficiency (47.09%), and low combination index (0.59) under hypoxic conditions. Notably, the nanosystem can freely adjust the release of oxygen and damaging PHC NPs in an on-demand manner on the basis of the feedback of tumor activity. This feedback tumor therapy significantly improved the synergistic effect of PTT/PDT and reduced its toxic side effects. The in vivo antitumor results showed that the tumor inhibition rate of [PHC]PP@HA NPs with an on-demand oxygen supply of Hb was ∼100%, which was much better than those of PTT alone and Hb-free nanoparticles ([PC]PP@HA NPs). Consequently, the [PHC]PP@HA NP-mediated PTT/PDT guided by feedback tumor therapy achieved an efficient tumor ablation with an extremely low tumor recurrence rate (8.3%) 60 d later, indicating the versatile potential of PTT/PDT.

Multifunctional hypoxia imaging nanoparticles: multifunctional tumor imaging and related guided tumor therapy.

Hypoxia is a common feature of most solid tumors. Having a comprehensive understanding of tumor hypoxia condition is a key to tumor therapy. Many hypoxia imaging nanoparticles have been used for tumor detection. However, simple optical hypoxia imaging is not enough for tumor diagnosis. Also, the tumor therapy process needs the information about the tumor hypoxia condition. Recently, researchers developed multimodal hypoxia tumor imaging nanoparticles and multifunctional hypoxia imaging-guided tumor therapy nanoparticles. The multimodal hypoxia imaging could produce more tumor region information and engage in functional tumor imaging to better understand the tumor condition. The multifunctional hypoxia imaging-guided tumor therapy could monitor the tumor therapy process and evaluate tumor therapeutic effect. Meanwhile, many challenges and limitations are still remaining in the application of multifunctional hypoxia nanoparticles. In this review, we first introduce the types of multifunctional hypoxia imaging nanoparticles. Then we focus on multimodal hypoxia imaging nanoparticles and hypoxia imaging-guided tumor therapy nanoparticles. We also discuss the challenges and future perspectives of this field. There has not been many studies in this field for now. We hope this review would bring more researchers' attention to this field so that it would substantially contribute to tumor precise therapy.

A bimetallic sulfide CuCo2S4 with good synergistic effect was constructed to drive high performance photocatalytic hydrogen evolution.

In order to further improve the photocatalytic performance of the semiconductor photocatalyst, a photocatalytic hydrogen production performance was measured using a bimetallic sulfide photocatalyst. On this basis, the hydrogen production performance of the bimetallic sulfide CuCo2S4 (CCS-3) was compared with that of the single metal sulfides Cu31S16 and CoS2. The results showed that the bimetallic sulfide CCS-3 significantly improved the photocatalytic hydrogen production performance. The unique structure of the bimetallic sulfide CCS-3 made the photocatalytic activity of H2 2.47 times and 178.08 times higher than that of Cu31S16 and CoS2, respectively. In addition, the hydrogen production activity in CCS-3 was also very stable after XRD comparison before and after the reaction. The results of UV-visible diffuse reflectance spectroscopy showed that the visible light response range was significantly expanded, and the forbidden band width was smaller than that of Cu31S16 and CoS2. Photoluminescence spectroscopy results showed that CCS-3 had the best quenching effect because of its unique structure, which improved the separation efficiency and electron transfer efficiency of photogenerated electrons and holes. This article demonstrated new design strategies that would bring new insights into hydrogen evolution photocatalysts.

Molybdenum disulfide coated nickel-cobalt sulfide with nickel phosphide loading to build hollow core-shell structure for highly efficient photocatalytic hydrogen evolution.

A hollow spherical NiCo2S4 photocatalytic material was prepared with a high HER activity in the dye sensitization system. Then the hollow spherical NiCo2S4 was coated by the sheet-shaped 2D MoS2. Through the band gap adjustment, a type-II heterostructure is constructed to move the photogenerated electrons to the outer layer, and part of photogenerated holes migrate to the inner layer, which successfully reduces the degradation rate of the dye sensitizer for slowing down the decay of H2 evolution rate in the dye sensitization system. In addition, Ni2P was used to enrich photogenerated electrons on the outer layer of MoS2 thereby achieving more efficient hydrogen production. The photocatalytic materials were characterized by XRD, SEM, TEM, XPS, UV-vis DRS and N2 Isothermal adsorption experiments. The transfer mechanism of photogenerated carriers was studied by PL, photoelectrochemical tests, and hydroxyl radical capture experiments.

Thermochromism-induced temperature self-regulation and alternating photothermal nanohelix clusters for synergistic tumor chemo/photothermal therapy.

To improve the inherent defects of chemotherapy and photothermal therapy (PTT), we design a novel thermochromism-induced temperature self-regulation and alternating photothermal system based on iodine (I2)-loaded acetylated amylose nanohelix clusters (ILAA NHCs) under the guidance of molecular dynamic simulation in which I2 is loaded into the helical cavity of acetylated amylose (AA) by hydrophobic interaction. ILAA NHCs perform versatile photothermal conversion through their unique reversible thermochromism. Upon irradiation, I2 is gradually released and the ILAA NHCs turn into colorless. The laser is then penetrated deeply into the tissue for deep-seated heating, and the ILAA NHCs' color can be recovered by reversible thermochromism because of I2 reloading into the ILAA NHCs. When the process is repeated, the temperature can be controlled in a certain range. This alternating light-to-heat conversion significantly improve the effect of PTT. Meanwhile, I2 efficiently acts dual functions of chemotherapy and PTT. Results show that the photothermal depth by ILAA NHCs is 2.1-fold than other common photothermal agents (PTAs), and the irradiated region exhibits a lower surface temperature. In vitro and in vivo experiments both provide ILAA NHCs an excellent comprehensive antitumor effect with synergistic chemo/PTT, indicating versatile potential for tumor chemo/PTT.

Pretreatment lymphocyte-to-monocyte ratio as a predictor of survival among patients with ovarian cancer: a meta-analysis.

INTRODUCTION: In this meta-analysis, we analyzed retrospective cohort studies that assessed the prognostic potential of the pretreatment lymphocyte-to-monocyte ratio (LMR) among patients with ovarian cancer (OC). MATERIALS AND METHODS: We comprehensively searched electronic databases, including PubMed and Embase, from inception through October 2018. A random-effects model was used to calculate pooled HRs and their 95% CIs for overall survival (OS) and progression-free survival (PFS). The low LMR group was treated as the reference group. RESULTS: Twelve studies, including 3,346 OC cases at baseline, were included. Overall, our results indicated that LMR was positively associated with both OS (HR: 1.85, 95% CI: 1.50-2.28, P<0.001; I 2=76.5%) and PFS (HR: 1.70, 95% CI: 1.49-1.94, P<0.001; I 2=24.4%) among OC patients. Stratified analyses indicated that, for OS, the LMR's protective effect was more evident in studies conducted among younger patients (<55 years) than in those conducted among older patients (≥55 years; P for interaction =0.017), which was confirmed by meta-regression analysis (P=0.004). CONCLUSION: This study suggested that a higher pretreatment LMR level was associated with a favorable prognosis among OC patients. Future large-scale prospective clinical trials are needed to confirm the prognostic value of LMR among OC patients.

Progress of recyclable magnetic particles for biomedical applications.

Recyclable magnetic particles constitute a class of particles that can be manipulated by external magnetic fields and reused multiple times. These particles consist of a magnetic part and a functional part and have been widely used in the biomedical field, such as in enzyme immobilization, biochemical separation, nucleic acid detection and antibacterial agents, owing to their advantages of convenient operation, high efficiency, mild separation, and easy recycling. In this review, we investigate the research status of recyclable magnetic particles, and discuss their preparation methods, types and recycling methods in detail. According to their structure, existing recyclable magnetic particles are divided into three main types: core-shell structure particles, matrix-dispersed structure particles and hollow structure particles. Each type of recyclable magnetic particle requires a treatment procedure for reuse, which includes direct reuse, washing treatment, chemical treatment and high-temperature calcination. To date, most recycling methods for magnetic particles belong to washing and chemical treatment, and few studies focus on novel magnetic recycling methods, owing to the lack of systemic summary and theoretical studies. We also point out the limitations of preparation and treatment methods, and predict the development direction of recyclable magnetic particles. We predict that recyclable magnetic particles will occupy an important position in the field of sustainable development and environmental protection, and considerable perspectives will be presented for the development of recyclable magnetic particles.