Polypropylene anterior-apical single-incision UPHOLD-LITE mesh surgery in women with severe pelvic organ prolapse: Outcome at 53 months follow up.

BACKGROUND AND PURPOSE: We present this current study to complement with mesh inlays plausible benefits (UPHOLD-LITE System) on available long-term study amidst FDA's concern on mesh complications. This study aims to assess the medium-term outcomes of UPHOLD-LITE system for treatment of advanced pelvic organ prolapse (POP) and its complications, and lower urinary tract symptoms. METHODS: This is a retrospective case series of 53 months follow-up of 123 consecutive patients who underwent UPHOLD-LITE system. Objective outcome measures the anatomical correction of prolapse with POP-Q ≤ Stage 1. Subjective outcome was patient's feedback to questions 2 and 3 of POPDI-6. Secondary outcome measures the quality of life, presence of lower urinary tract symptoms and complications. Quality of life is assessed by validated questionnaires on Urogenital Distress Inventory 6 (UDI-6), Incontinence Impact Questionnaire 7 (IIQ-7), Pelvic Organ Prolapse Distress Inventory 6 (POPDI-6), and Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire 12 (PISQ-12) at 1 and 3 years post-operatively. RESULTS: Objective outcome at 1 and 3 years was at 96.7 % and 95.4 % respectively. The subjective cure was 95.1 % and 91.6 %. Five-year cumulative cure rate maintained at 87.2 %. Secondary outcomes observed improvement on UDI-6, IIQ-7, POPDI-6 and PISQ-12 postoperatively. Bladder outlet obstruction improved while de novo urodynamic stress incontinence (USI) increased slightly post surgically. Mesh erosion rate was 0.8 %. CONCLUSION: The UPHOLD-LITE system demonstrated good medium term anatomical correction of apical and anterior prolapse, with good subjective cure and improved quality of life. Whilst complication rate was low, slight increase in de novo USI was observed.

Multifunctional Hollow Porous Fe3O4@N-C Nanocomposites as Anodes of Lithium-Ion Battery, Adsorbents and Surface-Enhanced Raman Scattering Substrates.

At present, it is still a challenge to prepare multifunctional composite nanomaterials with simple composition and favorable structure. Here, multifunctional Fe3O4@nitrogen-doped carbon (N-C) nanocomposites with hollow porous core-shell structure and significant electrochemical, adsorption and sensing performances were successfully synthesized through the hydrothermal method, polymer coating, then thermal annealing process in nitrogen (N2) and lastly etching in hydrochloric acid (HCl). The morphologies and properties of the as-obtained Fe3O4@N-C nanocomposites were markedly affected by the etching time of HCl. When the Fe3O4@N-C nanocomposites after etching for 30 min (Fe3O4@N-C-3) were applied as the anodes for lithium-ion batteries (LIBs), the invertible capacity could reach 1772 mA h g-1 after 100 cycles at the current density of 0.2 A g-1, which is much better than that of Fe3O4@N-C nanocomposites etched, respectively, for 15 min and 45 min (948 mA h g-1 and 1127 mA h g-1). Additionally, the hollow porous Fe3O4@N-C-3 nanocomposites also exhibited superior rate capacity (950 mA h g-1 at 0.6 A g-1). The excellent electrochemical properties of Fe3O4@N-C nanocomposites are attributed to their distinctive hollow porous core-shell structure and appropriate N-doped carbon coating, which could provide high-efficiency transmission channels for ions/electrons, improve the structural stability and accommodate the volume variation in the repeated Li insertion/extraction procedure. In addition, the Fe3O4@N-C nanocomposites etched by HCl for different lengths of time, especially Fe3O4@N-C-3 nanocomposites, also show good performance as adsorbents for the removal of the organic dye (methyl orange, MO) and surface-enhanced Raman scattering (SERS) substrates for the determination of a pesticide (thiram). This work provides reference for the design and preparation of multifunctional materials with peculiar pore structure and uncomplicated composition.

In-situ fabrication of novel Au nanoclusters-Cu2+@sodium alginate/hyaluronic acid nanohybrid gels for cuproptosis enhanced photothermal/photodynamic/chemodynamic therapy via tumor microenvironment regulation.

Multimodal combined therapy (MCT) is an emerging avenue to eliminate tumor cells by the synergistic effect of various therapeutic methods. However, the complex tumor microenvironment (TME) is becoming the key barrier to the therapeutic effect of MCT due to the excessive existence of H+ ions, H2O2, and glutathione (GSH), the lack of O2, and the relaxation of ferroptosis. To overcome these limitations, smart nanohybrid gels with excellent biocompatibility, stability and targeting function were prepared by using gold nanoclusters as cores and an in situ cross-linking composite gel of sodium alginate (SA)/hyaluronic acid (HA) as the shell. The obtained Au NCs-Cu2+@SA-HA core-shell nanohybrid gels possessed near-infrared light response synergistically benefitting photothermal imaging guided photothermal therapy (PTT) and photodynamic therapy (PDT). Meanwhile, the H+-triggered release of Cu2+ ions from the nanohybrid gels not only induces cuproptosis to avoid the relaxation of ferroptosis, but also catalyzes H2O2 in the TME to generate O2 to simultaneously improve the hypoxic microenvironment and PDT effect. Furthermore, the released Cu2+ ions could consume the excessive GSH to form Cu+ ions effectively, which caused the formation of hydroxyl free radicals (·OH) to kill tumor cells, synergistically realizing GSH consumption-enhanced PDT and chemodynamic therapy (CDT). Hence, the novel design in our work provides another research avenue for cuproptosis-enhanced PTT/PDT/CDT via TME modulation.

Face-specific negative bias of aesthetic perception in depression: Behavioral and EEG evidence.

Introduction: Symptoms of depression are associated with the dysfunction of neural systems such as the emotion, reward system, and the default mode network. These systems were suggested by the model of neuroaesthetics as key contributions to aesthetic experience, leading to the prediction of atypical aesthetic orientation in depression. Here we investigated the aesthetic characteristics of depression and the corresponding neural underpinnings. Methods: Fifty-two (25 depression patients, 27 healthy controls) participants were asked to make aesthetic judgments on faces and landscapes in an electroencephalographic (EEG) experiment. Results: Our results indicate that relative to the controls, the depression tended to give ugly judgments and refrained from giving beautiful judgments, which was observed only for faces but not for landscapes. We also found that the face-induced component N170 was more negative in the depression group than the control group for ugly and neutral faces. Moreover, the aesthetic evaluation of ugly faces was associated with decreased N200 negativity in the depression group than in the control group, while the evaluation of beautiful faces was associated with decreased brain synchronization at the theta band. Discussion: These results suggested a face-specific negative aesthetic bias in depression which can help to design and develop aesthetics-oriented schemes in assisting the clinical diagnosis and therapy of depression.

Fabrication of porous ZnO/Co3O4 nanohybrids for the application of surface enhanced Raman scattering.

With the growing use of various pesticides, it is important to develop facile and sensitive method to detect pesticides residues in food. Here, a semiconductor/magnetic hybrid material was used as surface enhanced Raman scattering (SERS) substrate to detect simulated residues. The representative sample of porous ZnO/Co3O4 nano-cube was fabricated by pyrolysis and calcination of Zn-Co ZIF, successively. The obtained hybrid of ZnO/Co3O4 was employed as substrate to detect of crystal violet (CV) and Rhodamine B (Rh B), and showed remarkable SERS performance. The detection limit of Rh B was 1 × 10-10 M as well as CV of 1 × 10-9 M. The results indicated that it was an ideal choice to improve the SERS property of transition metal oxide substrates by doping semiconductor. The semiconductor/magnetic hybrid material highlighted the obvious characteristics of low cost, facile preparation and ultra-low detection limit in the SERS measurements. The hybrids with the combination of semiconductor/magnetic properties showed a further widely application and development in SERS detection of pesticides residues.

Accuracy of genomic selection for alfalfa biomass yield in two full-sib populations.

Alfalfa (Medicago sativa) is one of the most important leguminous forages, widely planted in temperate and subtropical regions. As a homozygous tetraploid, its complex genetic background limits genetic improvement of biomass yield attributes through conventional breeding methods. Genomic selection (GS) could improve breeding efficiency by using high-density molecular markers that cover the whole genome to assess genomic breeding values. In this study, two full-sib F1 populations, consisting of 149 and 392 individual plants (P149 and P392), were constructed using parents with differences in yield traits, and the yield traits of the F1 populations were measured for several years in multiple environments. Comparisons of individual yields were greatly affected by environments, and the best linear unbiased prediction (BLUP) could accurately represent the original yield data. The two hybrid F1 populations were genotyped using GBS and RAD-seq techniques, respectively, and 47,367 and 161,170 SNP markers were identified. To develop yield prediction models for a single location and across locations, genotypic and phenotypic data from alfalfa yields in multiple environments were combined with various prediction models. The prediction accuracies of the F1 population, including 149 individuals, were 0.11 to 0.70, and those of the F1 population, consisting of 392 individuals, were 0.14 to 0.67. The BayesC and RF models had the highest average prediction accuracy of 0.60 for two F1 populations. The accuracy of the prediction models for P392 was higher than that of P149. By analyzing multiple prediction models, moderate prediction accuracies are obtained, although accuracies will likely decline across multiple locations. Our study provided evidence that GS can accelerate the improvement of alfalfa yield traits.

Facile Synthesis of Fe3O4@Au/PPy-DOX Nanoplatform with Enhanced Glutathione Depletion and Controllable Drug Delivery for Enhanced Cancer Therapeutic Efficacy.

The complex physiological environment and inherent self-healing function of tumors make it difficult to eliminate malignant tumors by single therapy. In order to enhance the efficacy of antitumor therapy, it is significant and challenging to realize multi-mode combination therapy by utilizing/improving the adverse factors of the tumor microenvironment (TME). In this study, a novel Fe3O4@Au/PPy nanoplatform loaded with a chemotherapy drug (DOX) and responsive to TME, near-infrared (NIR) laser and magnetic field was designed for the combination enhancement of eliminating the tumor. The Fe2+ released at the low pH in TME can react with endogenous H2O2 to induce toxic hydroxyl radicals (·OH) for chemodynamic therapy (CDT). At the same time, the generated Fe3+ could deplete overexpressed glutathione (GSH) at the tumor site to prevent reactive oxygen species (ROS) from being restored while producing Fe2+ for CDT. The designed Fe3O4@Au/PPy nanoplatform had high photothermal (PT) conversion efficiency and photodynamic therapy (PDT) performance under NIR light excitation, which can promote CDT efficiency and produce more toxic ROS. To maximize the cancer-killing efficiency, the nanoplatform can be successfully loaded with the chemotherapeutic drug DOX, which can be efficiently released under NIR excitation and induction of slight acidity at the tumor site. In addition, the nanoplatform also possessed high saturation magnetization (20 emu/g), indicating a potential magnetic targeting function. In vivo and in vitro results identified that the Fe3O4@Au/PPy-DOX nanoplatform had good biocompatibility and magnetic-targeted synergetic CDT/PDT/PTT/chemotherapy antitumor effects, which were much better than those of the corresponding mono/bi/tri-therapies. This work provides a new approach for designing intelligent TME-mediated nanoplatforms for synergistically enhancing tumor therapy.

A multi-responsive Au NCs@PMLE/Ca2+ antitumor hydrogel formed in situ on the interior/surface of tumors for PT imaging-guided synergistic PTT/O2-enhanced PDT effects.

At present, although phototherapy and related imaging have proven to be promising cancer diagnosis and treatment strategies, the free diffusion of photosensitizers into normal tissues can cause side effects, and the efficiency of photodynamic therapy (PDT) can also be limited by the tumor hypoxic microenvironment. Herein, we designed and prepared a new cancer nanoplatform containing Au nanoclusters (NCs)@Premna microphylla leaf extract (PMLE) with both responsiveness to near-infrared (NIR) laser irradiation and tumor microenvironment (TME) by facile redox and coordination reactions. Then, the Au NCs@PMLE/Ca2+ hydrogel was constructed in situ inside and on the surface of tumors for locoregional antitumor activity under 808 nm laser irradiation. The Au NCs@PMLE nanoplatform showed distinguished performance in killing cancer cells and alleviating tumor hypoxia by enhancing the temperature of the tumor sites and producing reactive oxygen species (ROS) under NIR irradiation as well as catalyzing hydrogen peroxide (H2O2) decomposition in TME for oxygen (O2) generation via catalase in PMLE. The ultra-small size of about 3 nm of the Au NCs in this nanoplatform was obtained using the biological molecules present in PMLE as reductants and coordination agents simultaneously, which also demonstrated the outstanding capability of photothermal (PT) imaging and photothermal therapy (PTT) towards tumors. Furthermore, the Au NCs@PMLE/Ca2+ hydrogel formed in situ through natural PMLE and intrinsic Ca2+ in TME could not only improve the biocompatibility of the nanoplatform and stability of Au NCs but was also highly concentrated around the tumor thus enhancing the therapeutic efficiency and inhibiting its migration to normal tissues, decreasing the side effects. The results of the experiments confirmed that the Au NCs@PMLE/Ca2+ hydrogel possessed PT imaging-guided NIR laser/TME-responsive synergetic cancer PTT/O2-enhanced PDT and remarkable locoregional antitumor effect for cancer therapy. This work may open a new versatile route for multi-responsive localized cancer therapeutic nanoplatforms.

The complete chloroplast genome of Medicago arabica (Fabaceae).

Medicago arabica (Linnaeus, 1762) Huds. is an important annual legume forage that grows in a wide range of climates, from subtropical to temperate. This study aimed to sequence the chloroplast genome of M. arabica and compare it with other legumes. In this study, we sequenced the entire chloroplast genome of M. arabica, which has 125,056 base pairs. The total GC content of the chloroplast genome of M. arabica was 34.4%. From the 110 unique genes of the circular genome, 30 tRNA genes, four rRNA genes, and 76 protein-coding genes were successfully annotated. A maximum likelihood (ML) tree was constructed using the model species and 17 species of the Medicago genus. M. arabica was shown to be phylogenetically closely related to M. polymorpha. The nucleotide diversity of the chloroplast genome may provide valuable molecular markers to study chloroplast, genetic breeding, and plant molecular evolution. These findings provide a solid foundation for future research on the molecular biology of the chloroplast.

The complete chloroplast genome of Medicago scutellata (Fabaceae).

Medicago scutellata (Linnaeus, 1753) is one of the essential leguminous forages distributed across tropical and subtropical regions of the world. In our study, we obtained the complete chloroplast genome of M. scutellata with a length of 124,082 bp. The total GC content of the entire chloroplast genome of M. scutellata was 33.9%. Among the 110 unique genes in the circular genome, 30 tRNA, 4 rRNA, and 76 protein-coding genes were successfully annotated. A phylogenetic tree constructed using common protein-coding genes revealed that M. scutellata is closely related to M. truncatula from the Fabaceae family.

Optical pressure and temperature sensing properties of Nd3+:YTaO4.

The pressure- and temperature-dependent luminescence properties of M'-phase Nd3+:YTaO4 synthesized by a molten salt method are presented. Ten near-infrared emission lines originating from the transitions between the two Stark levels R1,2 of the 3F3/2 state and the five Stark levels Z1,2,3,4,5 of the 4I9/2 state for the doped Nd3+ ions can be clearly identified. All these emission lines are found to shift linearly with pressure in a range up to ∼11 GPa. The R2,1 → Z5 emission lines have larger pressure sensitivities, which are 16.44 and 14.27 cm-1 GPa-1. The intensities of all the emission lines evolve with pressure non-monotonically, and peak at ∼1 GPa. The R1 → Z4,5 and R2 → Z1 emission lines can be obviously narrowed under the hydrostatic pressure, and broadened under the non-hydrostatic pressure, indicating their potential capability for reflecting the characteristic of a pressure environment. The intensity ratio of the R2,1 → Z5 emission lines exhibits a large temperature dependence, with a relative sensitivity between 0.129% and 0.108% K-1 in the physiological temperature range of 290-320 K. Thermal variations of the spectral positions and widths of the R2,1 → Z5 emission lines are also investigated. A high thermal stability for the position of the R2 → Z5 emission line is revealed. Based on the experimental results, the advantages and potential of Nd3+:YTaO4 as a multi-functional sensor for pressure and temperature are discussed.

De novo detrusor overactivity and urgency after mid-urethral slings for urodynamic stress incontinence.

INTRODUCTION AND HYPOTHESIS: The objective was to identify incidence and risk factors of de novo urgency and detrusor overactivity (DO) following mid-urethral slings (MUS) in patients with urodynamic stress incontinence (USI) without urgency. METHODS: A total of 688 women between January 2004 and July 2017 were reviewed retrospectively. De novo urgency was established with a positive response to question 2 on the Urogenital Distress Inventory-6 questionnaire (UDI-6). Objective cure of USI is no involuntary urine leakage during filling cystometry and pad test < 2 g. Subjective cure of stress urinary incontinence (SUI) is defined as a negative response to question 3 on UDI-6. Multivariate logistic regression was used to identify risk factors for failure. RESULTS: Forty-four out of 688 women (6.4%) developed de novo urgency, with 16 out of 688 (2.3%) demonstrating de novo DO. Subjective cure for women with de novo urgency was significantly lower at 35 out of 44 (79.5%) compared with 556 out of 644 (86.3%) in those with no urgency (p < 0.001). Objective cure for women with de novo DO was significantly lower at 8 out of 16 (50%) compared with 599 out of 672 (89.1%) in those with detrusor stability (p < 0.001). Quality of life improved for all. Age ≥ 66 (OR, 1.23; 1.07), increased bladder sensation (OR, 4.18; 3.80), lower bladder capacity (OR, 5.28; 4.97), lower maximum urethral closure pressure (OR, 2.32; 5.20), and pad test > 100 g (OR, 1.08; 1.15) were independent risk factors for de novo urgency and DO. Diabetes (OR, 1.32) was an independent predictor of de novo urgency. CONCLUSION: Cure is significantly reduced in women who report symptoms of de novo urgency or demonstrate DO after MUS at 1 year. Independent risk factors include age ≥ 66, increased bladder sensation, lower bladder capacity, lower maximum urethral closure pressure, greater pad loss, and diabetes.

Self-assembled Au4Cu4/Au25 NCs@liposome tumor nanotheranostics with PT/fluorescence imaging-guided synergetic PTT/PDT.

Exploring and developing a new type of nanoplatform with diagnosis and treatment to effectively cure tumors and reduce side effects has become a hot spot for researchers and is of great significance. Herein, a cancer theranostic nanoplatform with dual-imaging, dual-phototherapy and laser-responsiveness to tumor microenvironment was successfully assembled by liposome (Lip) co-loaded with oil-soluble Au4Cu4 nanoclusters (NCs) and water-soluble Au25 NCs via a simple film hydration method and subsequent extraction process. The prepared Au4Cu4/Au25@Lip nanoplatform with core-shell structure and about 50 nm of uniform sphere shape presented highly biocompatible, stability and passive targeting due to the enhanced permeability and retention (EPR) effect. Furthermore, the Lip composed of lecithin and cholesterol has good affinity with the cell membrane, which can realize the effective accumulation of photosensitizers at the tumor site, so that improving phototherapy effect and reducing the damage to normal tissue. The loaded oil-soluble Au4Cu4 NCs were firstly and pleasantly surprised to find possessed not only ideal photodynamic effect, but also preferable catalysis towards endogenous hydrogen peroxide (H2O2) decomposition to produce oxygen (O2) for improving the tumor hypoxic environment besides the excellent photoluminescence ability while the water-soluble Au25 NCs own outstanding photothermogenesis effect and also photoluminescence performance. The in vitro and in vivo experiment results proved that in the Au4Cu4/Au25@Lip nanoplatform, the performances of both NCs were complementary, which presenting considerable photothermal/fluorescence imaging (PTI/FI)-guided synergistic photothermal therapy (PTT)/O2-enhanced photodynamic therapy (PDT) effect for the tumor under the irradiation of near infrared (NIR) laser. This work provides a useful inspiration and paves a new way for the assembly of NCs or namomaterials with different properties into an integrated anti-tumor theranostic nanoplatform.

An effective NIR laser/tumor-microenvironment co-responsive cancer theranostic nanoplatform with multi-modal imaging and therapies.

Cancer is still a major threat to human health at present. Developing new types of integrated nanoplatforms for the accurate diagnosis and effective treatment of cancer is very significant. Herein, an intelligent dual-stage core-shell cancer theranostic nanoplatform (Fe3+@Au1Ag24@PbP) with NIR laser/tumor-microenvironment (TME) co-responsiveness and multi-modal imaging-therapy was successfully prepared, which was composed of the precisely structured oil-soluble Au1Ag24 nanoclusters (NCs) and Fe3+ ions easily assembled within the oil and aqueous phases of the polyethylene glycol (PEG) block grafted polyketal (PK) copolymer (PK-b-PEG, PbP) vesicles, respectively. In this system, we were delighted to find that the prepared Au1Ag24 NCs possess multi-photoresponsive properties, endowing the nanoplatform with photoacoustic (PA)/photothermal (PT) imaging and synergetic photothermal therapy (PTT)/photodynamic therapy (PDT) for cancer under near-infrared (NIR) laser irradiation. On the other hand, Fe3+ ions exhibit multi-TME response and regulation behaviors, including as catalysts for the decomposition of endogenous hydrogen peroxide (H2O2) in the solid tumor to produce O2 and as the oxidizing agent for the consumption of the intracellular GSH to avoid the reduction of the generated 1O2; therefore, the synchronously formed Fe2+ ions from the redox of Fe3+ with GSH could further react with H2O2 to produce hydroxyl radical (˙OH), which induced ferroptosis-based cancer treatment. The PbP shell possesses TME/pH sensitivity for controlled drug release and passive targeting, causing a large increase in Au1Ag24/Fe3+ accumulation within the weakly acidic tumor region and reducing the side effects on normal tissues. Both in vitro and in vivo experiments demonstrate that the Fe3+@Au1Ag24@PbP nanoplatform presented excellent PA/PT imaging-guided synergetic PTT/PDT/ferroptosis effects toward tumor cells and tumors. This integrating multi-responsive and multi-modal theranostic nanoplatform paves a new way for effective cancer therapy.

Ultrabright Au@Cu14 nanoclusters: 71.3% phosphorescence quantum yield in non-degassed solution at room temperature.

The photoluminescence of metal nanoclusters is typically low, and phosphorescence emission is rare due to ultrafast free-electron dynamics and quenching by phonons. Here, we report an electronic engineering approach to achieving very high phosphorescence (quantum yield 71.3%) from a [Au@Cu14(SPh t Bu)12(PPh(C2H4CN)2)6]+ nanocluster (abbreviated Au@Cu 14 ) in non-degassed solution at room temperature. The structure of Au@Cu 14 has a single-Au-atom kernel, which is encapsulated by a rigid Cu(I) complex cage. This core-shell structure leads to highly efficient singlet-to-triplet intersystem crossing and suppression of nonradiative energy loss. Unlike the phosphorescent organic materials and organometallic complexes-which require de-aerated conditions due to severe quenching by air (i.e., O2)-the phosphorescence from Au@Cu 14 is much less sensitive to air, which is important for lighting and biomedical applications.

Dysregulation of phospholipase and cyclooxygenase expression is involved in Schizophrenia.

BACKGROUND: Schizophrenia (SZ) is a severe mental disease with highly heterogeneous clinical manifestations and pathological mechanisms. Schizophrenia is linked to abnormalities in cell membrane phospholipids and blunting of the niacin skin flush response, but the associations between these phenotypes and its molecular pathogenesis remain unclear. This study aimed to describe the PLA2/COX pathway, the key link between phospholipids and niacin flush, and to illustrate the pathogenic mechanisms in schizophrenia that mediate the above phenotypes. METHODS: A total of 166 patients with schizophrenia and 54 healthy controls were recruited in this study and assigned to a discovery set and a validation set. We assessed the mRNA levels of 19 genes related to the PLA2/COX cascade in leukocytes by real-time PCR. Plasma IL-6 levels were measured with an ELISA kit. Genetic association analysis was performed on PLA2G4A and PTGS2 to investigate their potential relationship with blunted niacin-skin response in an independent sample set. FINDINGS: Six of the 19 genes in the PLA2/COX pathway exhibited significant differences between schizophrenia and healthy controls. The disturbance of the pathway indicates the activation of arachidonic acid (AA) hydrolysis and metabolization, resulting in the abnormalities of membrane lipid homeostasis and immune function, further increasing the risk of schizophrenia. On the other hand, the active process of AA hydrolysis from cell membrane phospholipids and decreased transcription of CREB1, COX-2 and PTGER4 may explain the reported findings of a blunted niacin response in schizophrenia. The significant genetic associations between PLA2G4A and PTGS2 with the niacin-skin responses further support the inference. INTERPRETATION: These results suggested that the activation of AA hydrolysis and the imbalance in COX-1 and COX-2 expression are involved in the pathogenesis of schizophrenia and blunting of the niacin flush response. FUNDING: This work was supported by the National Key R&D Program of China (2016YFC1306900, 2016YFC1306802); the National Natural Science Foundation of China (81971254, 81771440, 81901354); Interdisciplinary Program of Shanghai Jiao Tong University (ZH2018ZDA40, YG2019GD04, YG2016MS48); Grants of Shanghai Brain-Intelligence Project from STCSM (16JC1420500); Shanghai Key Laboratory of Psychotic Disorders (13DZ2260500); and Shanghai Municipal Science and Technology Major Project (2017SHZDZX01); China Postdoctoral Science Foundation (2018M642029, 2018M630442, 2019M661526, 2020T130407); Natural Science Foundation of Shanghai (20ZR1426700); and Startup Fund for Youngman Research at SJTU (19 × 100040033).

4-in-1 Fe3O4/g-C3N4@PPy-DOX nanocomposites: Magnetic targeting guided trimode combinatorial chemotherapy/PDT/PTT for cancer.

At present, cancer has become a major disease threatening human health worldwide. Therefore, developing targeting guided multimode synergetic therapy has become one of the hot spots in current antitumor research and is also a great challenge. Herein, a new Fe3O4/g-C3N4@PPy-DOX nanocomposite containing magnetic iron oxide (Fe3O4) nanoparticles (NPs), lamellar structure of graphite-like carbon nitride (g-C3N4) and polypyrrole (PPy) shell with the loaded anti-tumor drug doxorubicin hydrochloride (DOX) was designed and prepared. The monodisperse Fe3O4 nanoparticles (NPs) with the diameter of 20 nm endowed the nanocomposite with the magnetic targeting ability, reducing damage to normal tissues. It is very interesting that the Fe3O4 NPs also possessed photosensitizer function for photodynamic therapy (PDT). The g-C3N4 sheets as the photocatalysis towards the degradation of water for generating O2 could effectively improve the hypoxia of solid tumors and increase the efficiency of PDT. In addition, PPy has high light-to-heat conversion efficiency, so was chosen for the cancer photothermal therapy (PTT). Finally, an anticancer drug (DOX) was loaded on the nanocomposite because the presence of mesoporous structure. Thus, the prepared Fe3O4/g-C3N4@PPy-DOX nanocomposites exhibit synergetic chemotherapy/PTT/enhanced PDT antitumor effect. This study provides an inspiration for combining targeting and multimodality to improve the anticancer efficiency.

[Establishment and validation of a risk prediction model for intensive care unit-acquired weakness].

OBJECTIVE: To explore the risk factors of intensive care unit-acquired weakness (ICU-AW), and to establishment and verify its risk prediction model. METHODS: A modeling group of 231 patients who met the inclusion criteria and were admitted to the intensive care unit (ICU) of the First Hospital of Jiaxing from July 2019 to June 2020 was collected by convenience sampling method. According to whether they developed ICU-AW, they were divided into ICU-AW group (55 cases) and non ICU-AW group (176 cases). The clinical data were collected concerning patients' individual information, disease-related factors, treatment-related factors and laboratory indicators, and the differences of the above indexes between two groups were compared. Logistic regression was used to analyze the ICU-AW risk factors and a risk prediction model was constructed. Calculate the area under ROC curve (AUC) to test the prediction effect of the model. At the same time, 60 patients who admitted to ICU from July to October 2020 and met the standards were collected to verify the model. RESULTS: Compared with non ICU-AW group, there were more males in ICU-AW group [61.8% (34/55) vs. 44.3% (78/176), P < 0.05], with higher levels of systemic inflammatory response syndrome (SIRS), sepsis, immobilization and the use of neuromuscular blockers [SIRS: 30.9% (17/55) vs. 3.4% (6/176), sepsis: 12.7% (7/55) vs. 2.3% (4/176), immobilization: 72.7% (40/55) vs. 39.2% (69/176), the use of neuromuscular blockers: 50.9% (28/55) vs. 14.2% (25/176), all P < 0.05], and acute physiology and chronic health evaluation II (APACHE II) score, blood lactic acid level and duration of mechanical ventilation, length of hospital stay were all increased [APACHE II score: 18 (15, 24) vs. 12 (8, 17), blood lactic acid (mmol/L): 2 (1, 2) vs. 1 (1, 2), duration of mechanical ventilation (days): 7 (4, 12) vs. 2 (2, 5), length of hospital stay (days): 10 (6, 16) vs. 5 (3, 9), all P < 0.05]. SIRS, APACHE II score, duration of mechanical ventilation and blood lactic acid were included to construct a risk prediction model [odds ratio (OR) values were 4.835, 1.083, 1.210, 1.790, P values were 0.018, 0.013, 0.015, 0.013]. The model equation was P = exp [-5.207+(1.576×SIRS)+(0.079×APACHE II)+(0.191×duration of mechanical ventilation)+(0.582×blood lactic acid)]. Internal verification: Calibration diagram showed the calibration curve above the ideal curve, AUC = 0.888, 95% confidence interval (95%CI) was 0.839-0.938; when the cut-off value was 0.166, the sensitivity was 89.1%, the specificity was 75.6%, and the maximum index was 0.649. External verification: Calibration diagram showed that the calibration curve was above the ideal curve, and the plotted AUC = 0.853, 95%CI was 0.753-0.953. When the cut-off value of the corresponding predictive risk value was 0.367, the sensitivity was 68.8%, the specificity was 86.4%, and the maximum approximate index was 0.552. CONCLUSIONS: The risk prediction model of ICU-AW constructed in this study has good consistency and prediction efficiency, which can provide reference for medical personnel to identify high-risk groups of ICU-AW patients in the early stage and provide targeted interventions in advance.

A dual-targeting Fe3O4@C/ZnO-DOX-FA nanoplatform with pH-responsive drug release and synergetic chemo-photothermal antitumor in vitro and in vivo.

Designing a proper intelligent platform to target cancer cells accurately and reducing its toxic side effects on normal tissues remain a challenge in medicine application. Herein, a novel dual-targeted and tumor microenvironment-triggered Fe3O4@carbon(C)/ZnO-doxorubicin (DOX) -folic acid (FA) drug delivery system with porous structure was designed and fabricated for the first time. The co-presence of Fe3O4 core and FA molecules functioned successfully could successfully realize the magnetic targeting and cancer cell-specific targeting. In addition, pH-responsive ZnO and porous carbon both derived directly from zinc-2-methylimidazolate complex (Zn-ZIF) could play the roles of "gatekeeper" and photothermal agent, respectively. The former could efficiently block the drug within mesoporous in blood environment for decreasing the damage to the normal tissues and achieving the controlled DOX release in the simulated and real acidic tumor microenvironment. And the latter could exhibit the intrinsic photothermal conversion efficiency upon 638 nm laser irradiation. Therefore, the Fe3O4@C/ZnO-DOX-FA nanoplatform integrated dual targeting, controlled chemotherapy with photothermal therapy (PTT) for cancer, displaying a significantly superior synergistic anticancer efficiency both in vitro and in vivo experiments to either monotherapy. Above results suggested the prepared nanoplatforms might be a promising candidate for effectively synergetic therapeutics to cancers.