Improved Photodynamic Therapy Based on Glutaminase Blockage via Tumor Membrane Coated CB-839/IR-780 Nanoparticles.

Photodynamic therapy (PDT) has promising applications. However, the lethal function of reactive oxygen species (ROS) produced during PDT is typically limited. This restriction is induced by oxygen shortage in the tumor microenvironment due to tumor cell hypermetabolism and reductive chemicals overexpression in tumor tissues. Glutamine (Gln) metabolism is crucial for malignancy development and is closely associated with redox. Herein, a novel nanoparticle (NP) named IRCB@M is constructed to boost PDT through dual effects. This NP simultaneously blocks aerobic respiration and inhibits cellular reduced substances by blocking the Gln metabolic pathway. Within the nanocomplex, a photosensitizer (IR-780) and a glutaminase inhibitor (CB-839) are self-assembled and then encapsulated by cancer cell membranes for homologous targeting. The Gln metabolism intervention relieves hypoxia and decreases the levels of nicotinamide adenine dinucleotide phosphate (NADPH) as well as reduced glutathione (GSH) in vitro and in vivo, which are the dual amplification effects on the IR-780-mediated lethal PDT. The antitumor effects against gastric cancer are ultimately evoked in vivo, thus offering a novel concept for enhancing PDT and other ROS-dependent therapeutic approaches.

Association of the composite dietary antioxidant index with bone mineral density in the United States general population: data from NHANES 2005-2010.

INTRODUCTION: There is evidence that individual antioxidants may increase bone mineral density (BMD) in patients with low BMD. However, the association between overall dietary antioxidant intake and BMD is unclear. The objective of this study was to examine how overall dietary antioxidant intake is related to BMD. MATERIALS AND METHODS: A total of 14,069 people participated in the National Health and Nutrition Examination Survey (NHANES) between 2005 and 2010. Dietary Antioxidant Index (DAI) was calculated from the intake of vitamins A, C, E, zinc, selenium, and magnesium, which indicates a nutritional tool to assess the overall antioxidant properties of the diet. The correlation between the Composite Dietary Antioxidant Index (CDAI) and BMD was examined using multivariate logistic regression models. In addition to fitting smoothing curves, we fitted generalized additive models as well. Furthermore, to ensure data stability and avoid confounding factors, subgroup analysis was also conducted on gender and body mass index (BMI). RESULTS: A significant association was demonstrated by the study between CDAI and total spine BMD (ß = 0.001, 95% CI 0-0.001, P = 0.00039). And just like that, CDAI was positively correlated with femoral neck (ß = 0.003, 95% CI 0.003-0.004, P < 0.00001) and trochanter (ß = 0.004, 95% CI 0.003-0.004, P < 0.00001). In the gender subgroup analysis, CDAI maintained a strong positive correlation with femoral neck and trochanter BMD in males and females. Nevertheless, the link with total spine BMD was only observed in males. In addition, in the subgroup analysis stratified by BMI, CDAI showed a significantly positive relation to BMD of the femoral neck and trochanter in each group. However, the significant relationship between CDAI and BMD of the total spine was only maintained when BMI was above 30 kg/m2. CONCLUSION: This study found that CDAI correlated positively with femoral neck, trochanter, and total spine BMD. This suggests that intake of a diet rich in antioxidants can reduce the risk of low bone mass and osteoporosis.

Young Sca-1+ bone marrow stem cell-derived exosomes preserve visual function via the miR-150-5p/MEKK3/JNK/c-Jun pathway to reduce M1 microglial polarization.

BACKGROUND: Polarization of microglia, the resident retinal immune cells, plays important roles in mediating both injury and repair responses post-retinal ischemia-reperfusion (I/R) injury, which is one of the main pathological mechanisms behind ganglion cell apoptosis. Aging could perturb microglial balances, resulting in lowered post-I/R retinal repair. Young bone marrow (BM) stem cell antigen 1-positive (Sca-1+) cells have been demonstrated to have higher reparative capabilities post-I/R retinal injury when transplanted into old mice, where they were able to home and differentiate into retinal microglia. METHODS: Exosomes were enriched from young Sca-1+ or Sca-1- cells, and injected into the vitreous humor of old mice post-retinal I/R. Bioinformatics analyses, including miRNA sequencing, was used to analyze exosome contents, which was confirmed by RT-qPCR. Western blot was then performed to examine expression levels of inflammatory factors and underlying signaling pathway proteins, while immunofluorescence staining was used to examine the extent of pro-inflammatory M1 microglial polarization. Fluoro-Gold labelling was then utilized to identify viable ganglion cells, while H&E staining was used to examine retinal morphology post-I/R and exosome treatment. RESULTS: Sca-1+ exosome-injected mice yielded better visual functional preservation and lowered inflammatory factors, compared to Sca-1-, at days 1, 3, and 7 days post-I/R. miRNA sequencing found that Sca-1+ exosomes had higher miR-150-5p levels, compared to Sca-1- exosomes, which was confirmed by RT-qPCR. Mechanistic analysis found that miR-150-5p from Sca-1+ exosomes repressed the mitogen-activated protein kinase kinase kinase 3 (MEKK3)/JNK/c-Jun axis, leading to IL-6 and TNF-α downregulation, and subsequently reduced microglial polarization, all of which contributes to reduced ganglion cell apoptosis and preservation of proper retinal morphology. CONCLUSION: This study elucidates a potential new therapeutic approach for neuroprotection against I/R injury, via delivering miR-150-5p-enriched Sca-1+ exosomes, which targets the miR-150-5p/MEKK3/JNK/c-Jun axis, thereby serving as a cell-free remedy for treating retinal I/R injury and preserving visual functioning.

The evolution of narrative identity in a "returning home" man: The psychological and cultural place of farming in the Chinese psyche.

OBJECTIVE: This study attempts to illustrate the process of reconstructing adaptive self-identity by tracking the development of imagery in Mr. Z's dreams and sandtrays. METHOD: The authors adopted amplification and Narrative Identity Process Analysis methods, and developed an Imagery NPCS tool to analyze the farming images in therapy sessions. RESULTS: It provided insights into Chinese culture from an applied, non-Western lens on identity theory. The subject of the study was a Chinese man who had lost his social identity due to stressful events, the results of which were reflected in the interplay between his personal narrative related to farming images and their cultural narrative framework. CONCLUSIONS: The authors propose a practical mode of developing narrative identity based on the dynamic organizing principle of opposites which are united in a persona-shadow personality system. Development of an integrated narrative identity can be facilitated by the dialectic between the cultural narrative offered by the psychotherapist and the client's personal narrative.

Multi-Responsive Molecular Encapsulation and Release Based on Hydrogen-Bonded Azo-Macrocycle.

Research on stimuli-responsive host-guest systems is at the cutting edge of supramolecular chemistry, owing to their numerous potential applications such as catalysis, molecular machines, and drug delivery. Herein, we present a multi-responsive host-guest system comprising azo-macrocycle 1 and 4,4'-bipyridinium salt G1 for pH-, photo-, and cation- responsiveness. Previously, we reported a novel hydrogen-bonded azo-macrocycle 1. The size of this host can be controlled through light-induced E↔Z photo-isomerization of the constituent azo-benzenes. The host is found in this work to be capable of forming stable complexes with bipyridinium/pyridinium salts, and implementing guest capture and release with G1 under light in a controlled manner. The binding and release of the guest in the complexes can also be easily controlled reversibly by using acid and base. Moreover, the cation competition-induced dissociation of the complex 1a2⊃G1 is achieved. These findings are expected to be useful in regulating encapsulation for sophisticated supramolecular systems.

Influence of optical zone on myopic correction in small incision lenticule extraction: a short-term study.

BACKGROUND: To evaluate the influence of preoperative optical zone on myopic correction in small incision lenticule extraction. METHODS: In this retrospective clinical study, 581 eyes from 316 patients underwent SMILE were selected, including 117 eyes in the small optical zone group (range from 6.0 to 6.4 mm) and 464 eyes in the large optical zone group (range from 6.5 to 6.8 mm). The measurements included uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), spherical, and cylinder were measured preoperatively and 3 months postoperatively. Propensity score match (PSM) analysis was performed with age, gender, eye (right/left), keratometry and preoperative spherical equivalent between two different groups. The influence of optical zones on postoperative refractive outcomes were evaluated using univariate regression analysis. RESULTS: In total, 78 pairs of eyes were selected by PSM (match ratio 1:1). There were no differences in the age, gender, eye (right/left), keratometry or preoperative spherical equivalent between the small and large optical zone groups. However, the difference of postoperative spherical equivalent was significantly between groups. Patients with larger optical zones had a trend towards less undercorrection (P = 0.018). Univariate linear regression model analysis found that each millimeter larger optical zone resulted in 8.13% or 0.39D less undercorrection (P < 0.001). The dependency between the optical zones and postoperative spherical equivalent was significant in the higher preoperative myopia group (r = 0.281, P < 0.001), but not significant in the lower myopia group (r = 0.028, P = 0.702). CONCLUSION: The diameter of optical zones would affect postoperative refractive outcomes in small incision lenticule extraction. This study indicated that larger optical zones induced less undercorrection, especially in patients with high myopia.

Comparison of short-term outcomes between robotic-assisted and laparoscopic gastrectomy guided by carbon nanoparticle suspension injection in gastric cancer.

BACKGROUND: The clinical application of robotic-assisted gastrectomy remains controversial, especially as clinical studies of this operation navigated by carbon nanoparticle suspension injection (CNSI) have not been conducted. This study aims to assess the perioperative safety and efficacy of CNSI-guided robotic-assisted gastrectomy in patients with gastric cancer by focusing on short-term outcomes. METHODS: A retrospective analysis of patients who underwent CNSI-guided laparoscopic or robotic-assisted gastrectomy with a pathological diagnosis of gastric cancer was conducted. Data on demographics, surgical management, clinical-pathological results and short-term outcomes were compared among the groups. RESULTS: A total of 126 eligible patients were separated into the robotic-assisted gastrectomy (RAG) group (n = 16) and the laparoscopic gastrectomy (LG) group (n = 110) in total. The operation time of the RAG group is longer than the LG group (p = 0.0000). When it comes to perioperative and short-term complications, there exists no statistical difference between the two groups. CONCLUSION: The time required for CNSI-guided robotic-assisted gastrectomy is longer than that for CNSI-guided laparoscopic gastrectomy. CNSI-guided robotic-assisted gastrectomy is safe and effective.

Hydrogen Sulfide and Its Donors: Keys to Unlock the Chains of Nonalcoholic Fatty Liver Disease.

Hydrogen sulfide (H2S) has emerged as the third "gasotransmitters" and has a crucial function in the diversity of physiological functions in mammals. In particular, H2S is considered indispensable in preventing the development of liver inflammation in the case of excessive caloric ingestion. Note that the concentration of endogenous H2S was usually low, making it difficult to discern the precise biological functions. Therefore, exogenous delivery of H2S is conducive to probe the physiological and pathological roles of this gas in cellular and animal studies. In this review, the production and metabolic pathways of H2S in vivo, the types of donors currently used for H2S release, and study evidence of H2S improvement effects on nonalcoholic fatty liver disease are systematically introduced.

On the Role of Alkali-Metal-Like Superatom Al12 P in Reduction and Conversion of Carbon Dioxide.

Developing efficient catalysts for the conversion of CO2 into fuels and value-added chemicals is of great significance to relieve the growing energy crisis and global warming. With the assistance of DFT calculations, it was found that, different from Al12 X (X=Be, Al, and C), the alkali-metal-like superatom Al12 P prefers to combine with CO2 via a bidentate double oxygen coordination, yielding a stable Al12 P(η2 -O2 C) complex containing an activated radical anion of CO2 (i.e., CO2 .- ). Thereby, this compound could not only participate in the subsequent cycloaddition reaction with propylene oxide but also initiate the radical reaction with hydrogen gas to form high-value chemicals, revealing that Al12 P can play an important role in catalyzing these conversion reactions. Considering that Al12 P has been produced in laboratory and is capable of absorbing visible light to drive the activation and transformation of CO2 , it is anticipated that this work could guide the discovery of additional superatom catalysts for CO2 transformation and open up a new research field of superatom catalysis.

Designing an alkali-metal-like superatom Ca3B for ambient nitrogen reduction to ammonia.

Converting earth-abundant nitrogen (N2) gas into ammonia (NH3) under mild conditions is one of the most important issues and a long-standing challenge in chemistry. Herein, a new superatom Ca3B was theoretically designed and characterized to reveal its catalytic performance in converting N2 into NH3 by means of density functional theory (DFT) computations. The alkali-metal-like identity of this cluster is verified by its lower vertical ionization energy (VIE, 4.29 eV) than that of potassium (4.34 eV), while its high stability was guaranteed by the large HOMO-LUMO gap and binding energy per atom (Eb). More importantly, this well-designed superatom possesses unique geometric and electronic features, which can fully activate N2via a "double-electron transfer" mechanism, and then convert the activated N2 into NH3 through a distal reaction pathway with a small energy barrier of 0.71 eV. It is optimistically hoped that this work could intrigue more endeavors to design specific superatoms as excellent catalysts for the chemical adsorption and reduction of N2 to NH3.

The short-term and long-term outcomes of indocyanine green tracer-guided laparoscopic radical gastrectomy in patients with gastric cancer.

BACKGROUND: The safety and efficacy of indocyanine green (ICG) imaging navigational laparoscopic gastrectomy remain controversial. This study is to evaluate the short-term and long-term outcomes of ICG-guided laparoscopic radial gastrectomy in patients with gastric cancer. METHODS: Consecutive patients with definitive diagnosis of gastric cancer that underwent laparoscopic radical gastrectomy were collected retrospectively. Propensity score matching (PSM) at 1:1 ratio was performed to compare the outcomes of two groups. RESULTS: A total of 122 qualified patients were divided into ICG group (n = 34) and non-ICG group (n = 88). PSM yielded 28 patients with comparable baseline characteristics into each group. The number of retrieved lymph node in ICG group was significantly higher than that in non-ICG group (P = 0.0196). There was no statistical difference of perioperative, short-term, and long-term complications between the two groups. CONCLUSION: ICG-guided laparoscopic radical gastrectomy is safe and effective, and ICG-navigated lymphadenectomy improves the number of retrieved lymph nodes for patients with gastric cancer.

Risk factors for lymph node metastasis in gastric neuroendocrine tumor: a retrospective study.

BACKGROUND: Lymph node metastasis (LNM) plays a vital role in the determination of clinical outcomes in patients with gastric neuroendocrine tumor (G-NET). Preoperative identification of LNM is helpful for intraoperative lymphadenectomy. This study aims to investigate risk factors for LNM in patients with G-NET. METHODS: We performed a retrospective study involving 37 patients in non-LNM group and 82 patients in LNM group. Data of demographics, preoperative lab results, clinical-pathological results, surgical management, and postoperative situation were compared between groups. Significant parameters were subsequently entered into logistic regression for further analysis. RESULTS: Patients in LNM group exhibited older age (p = 0.011), lower preoperative albumin (ALB) (p = 0.003), higher carcinoembryonic antigen (CEA) (p = 0.020), higher International normalized ratio (p = 0.034), longer thrombin time (p = 0.018), different tumor location (p = 0.005), higher chromogranin A positive rate (p = 0.045), and higher Ki-67 expression level (p = 0.002). Logistic regression revealed ALB (p = 0.043), CEA (p = 0.032), tumor location (p = 0.013) and Ki-67 (p = 0.041) were independent risk factors for LNM in G-NET patients. CONCLUSIONS: ALB, CEA, tumor location, and Ki-67 expression level correlate with the risk of LNM in patients with G-NET.

In Vitro and In Vivo Activity of 14-O-[(4,6-Diamino-pyrimidine-2-yl) thioacetyl] Mutilin against Methicillin-Resistant Staphylococcus aureus.

Staphylococcus aureus (S. aureus) is a major human pathogen that requires new antibiotics with unique mechanism. A new pleuromutilin derivative, 14-O-[(4,6-Diamino-pyrimidine-2-yl) thioacetyl] mutilin (DPTM), has been synthesized and proved as a potent antibacterial agent using in vitro and in vivo assays. In the present study, DPTM was further in vitro evaluated against methicillin-resistant Staphylococcus aureus (MRSA) isolated from dairy farms and outperformed tiamulin fumarate, a pleuromutilin drug used for veterinary. Moreover, a murine skin wound model caused by MRSA infection was established, and the healing effect of DPTM was investigated. The results showed that DPTM could promote the healing of MRSA skin infection, reduce the bacterial burden of infected skin MRSA and decrease the secretion of IL-6 and TNF-α inflammatory cytokines in plasma. These results provided the basis for further in-depth drug targeted studies of DPTM as a novel antibacterial agent.

Pharmacokinetics and Pharmacodynamics of Linezolid in Patients With Sepsis Receiving Continuous Venovenous Hemofiltration and Extended Daily Hemofiltration.

BACKGROUND: This prospective study compared pharmacokinetics (PK) and pharmacodynamics (PD) of linezolid in patients with sepsis receiving continuous venovenous hemofiltration (CVVH) with patients receiving extended daily hemofiltration (EDH). METHODS: Patients with sepsis treated with linezolid and CVVH or EDH were included. Serial blood samples were collected and linezolid concentrations measured. PKs were analyzed using Pmetrics. Monte Carlo simulations were used to evaluate PD target achievement. RESULTS: From 20 patients, 320 blood samples were collected for PK and PD analysis. PK profiles of linezolid were best described by a 2-compartment model. PK parameters were not significantly different between EDH and CVVH groups and were associated with body weight, renal replacement therapy (RRT) duration, and sequential organ failure assessment score. Monte Carlo simulations showed poor fractional target attainment for a minimum inhibitory concentration (MIC) of 2 mg/L with standard 600 mg intravenous administration every 12 hours. CONCLUSIONS: Patients with sepsis receiving RRT exhibited variability in PK/PD parameters for linezolid. PK parameters were not significantly different between CVVH- and EDH-treated patients. Higher probability of target attainment would be achievable at a MIC of 2 mg/L in EDH patients. Higher linezolid doses should be considered for patients on RRT to achieve adequate blood levels.

Coinage metalides: a new class of excess electron compounds with high stability and large nonlinear optical responses.

The possibility of using coinage metal atoms as excess electron acceptors is examined for the first time by designing a new class of M+-1-M'- (M = Li, Na, and K; M' = Cu, Ag, and Au) compounds termed "coinage metalides" on the basis of an intriguing Janus-type all-cis1,2,3,4,5,6-hexafluorocyclohexane (1) molecule. Under the large facial polarization of 1, the outermost ns1 electrons of alkali metal atoms can be transferred to coinage metal atoms, forming diffuse excess electrons around them. Consequently, the resulting M+-1-Cu- and M+-1-Ag- compounds exhibit significantly large nonlinear optical (NLO) responses. In particular, these novel M+-1-M'- compounds exhibit much higher stability (larger VIEs and Ec values) than that of the corresponding M+·1·M'- (M, M' = Li, Na, and K) alkalides. We hope this work could open up new possibilities for NLO material design by using coinage metal atoms as excess electron acceptors and, on the other hand, attract more experimental interest and efforts to synthesize such stable compounds in the laboratory.

Identification and Characterization of pantocin wh-1, a Novel Cyclic Polypeptide Produced by Pantoea dispersa W18.

Pantoea dispersa W18, isolated from contaminated soil, was found to exert antimicrobial activity against Mycobacterium species, including Mycobacterium tuberculosis, an important human pathogen. Here, the anti-mycobacterial compound produced by Pantoea dispersa W18 was purified by a combination of hydrophobic interaction chromatography, cation exchange chromatography, and reverse phase HPLC. Active compounds from Pantoea dispersa W18 were identified as a natural peptide named pantocin wh-1 with a 1927 Da molecular weight. The primary structure of this compound was detected by N-terminal amino acid sequencing. The amino acid sequence of pantocin wh-1 consisted of 16 amino acid residues with a cyclic structure. The pantocin wh-1 could be inactivated by protease K, but was heat stable and unaffected by pH (2-12). However, the activity was not completely inactivated by trypsin and pepsin. This is the first report of a cyclic polypeptide purified from a strain of Pantoea dispersa.

Characterization and genome analysis of novel Klebsiella phage Henu1 with lytic activity against clinical strains of Klebsiella pneumoniae.

Klebsiella pneumoniae is an important human pathogen that is associated with a wide range of diseases, including pneumonia and septicemia. Because of the threat of drug-resistant K. pneumoniae to humans, especially carbapenem-resistant K. pneumoniae, which is becoming a growing threat to hospitalized patients, the potential use of phage therapy has generated considerable interest. Henu1, isolated from a sewage sample, was identified as a linear double-stranded DNA phage of 40,352 bp with 53.14% G + C content and 143-bp terminal repeats. The Henu1 genome contains 45 open reading frames, and no tRNA genes were found. K. pneumoniae clinical strains with the capsular types K-1, K-2, and K-57 could be infected by Henu1. No human-virulence-related genes or lysogen-formation gene clusters were detected in this phage genome, suggesting that Henu1 is a virulent phage in its bacterial host and is safe for humans.

Can Coinage Metal Atoms Be Capable of Serving as an Excess Electron Source of Alkalides with Considerable Nonlinear Optical Responses?

Alkalides, as a representative kind of excess electron compounds, have been demonstrated to be potential nonlinear optical (NLO) materials with large static first hyperpolarizabilities (ß0). The possibility of utilizing coinage metal atoms as a novel excess electron source to design a series of alkalides, i.e., (M@36adz)M' (M = Cu, Ag, and Au; M' = Li, Na, and K), was examined by density functional theory calculations. The alkalide characteristics of these compounds are guaranteed by their HOMOs and VIE values as well as NBO analysis. In particular, all proposed alkalides exhibit considerable first hyperpolarizabilities (ß0) up to 61 590 au, indicating that they can be considered as novel NLO molecules of high performance. Moreover, a larger cage-complexant has been considered, and the resulting (Ag+@TriPip222)K- alkalide possesses a remarkably large ß0 value of 180 068 au. We hope that this work will provide a new recipe for designing excess electron compounds and, on the other hand, attract more research interest and efforts in exploring new, unconventional alkalides.

Preparation of Efficient BiOBr/MIL-88B(Fe) Composites with Enhanced Photocatalytic Activities.

In this study, a novel composite containing an iron based metal-organic framework (MOF) and BiOBr was successfully synthesized by a simple method, and was fully characterized by X-ray diffraction patterns, Fourier transform infrared spectra, UV-vis diffuse reflectance spectra, and transmission electron microscopy. Moreover, the photocatalytic activities of BiOBr/MIL-88B(Fe) composites and the pure materials were evaluated by measuring the degradation of Rhodamine B under visible light. The results show that the composite exhibits better photocatalytic activities than pure materials, which can be ascribed to the high adsorption capacity of MIL-88B(Fe) and the enhanced separation of photogenerated charge carriers from assembly of MIL-88B(Fe) on BiOBr. And the effects of various operating parameters such as catalyst dosage, medium pH, the mass ratio of BiOBr, and MIL-88B(Fe) and the dye initial concentration on the degradation of RhB have been studied.