Hypothyroidism and sinus dysfunction associated with lithium-paliperidone combination therapy for bipolar disorder with psychotic symptoms: a case report.

Background and aim: Lithium is considered to be the first-line treatment for bipolar disorder, and paliperidone was approved for the treatment of schizophrenia and acute bipolar manic/mixed episodes. However, both agents have been associated with thyroid dysfunction and cardiovascular adverse effects like subclinical hypothyroidism, bradycardia, and sinus arrest, even at therapeutic doses. Case presentation: Here, we reported a case of a 17-year-old Han Chinese female who developed symptomatic hypothyroidism, sinus bradycardia, and sinus arrest while being treated with lithium and paliperidone for bipolar disorder with psychotic features including auditory hallucinations. Her workup suggested that these adverse effects might be related to the combined lithium and paliperidone treatment, although other causes could not be ruled out. After discontinuing both medications, her thyroid function and heart rhythm normalized over 20 days. Conclusion: To our knowledge, hypothyroidism, sinus bradycardia, and sinus arrest associated with the combined use of lithium and paliperidone had not been reported previously. Further research is warranted to elucidate the potential risks and benefits of this combination therapy for bipolar disorder with psychotic symptoms.

Pillar arene Se nanozyme therapeutic systems with dual drive power effectively penetrated mucus layer combined therapy acute lung injury.

siRNA has demonstrated a promising paradigm for therapy of acute lung injury(ALI). However, the pulmonary mucus layer barrier powerfully hinders the therapeutic efficacy. Herein, we proposed to use dual drive power to enhance the mucus permeation of siRNA by constructing the neutral and targeted selenium nanozymes therapeutic system. The multifunctional selenium nanozymes (CWP-Se@Man) were synthesized by modifying with cationic water-soluble pillar arene (CWP) and mannose (Man). After loading CCR2-siRNA, the CWP-Se@Man reached electroneutrality that co-driven by electroneutrality and targeting, the mucus permeation capacity of CWP-Se@Man enhanced by ∼15 fold, thus effectively penetrate pulmonary mucus layer and deliver CCR2-siRNA into macrophages. Moreover, with optimizing the composition of CWP-Se@Man made of CWP (Slutsky, 2013) [5] or CWP (Ichikado et al., 2012) [6], the therapeutic system CWP (Ichikado et al., 2012) [6]-Se@Man showed better biological activities due to smaller size. In inflamed modes, the CWP-Se@Man nanotherapeutic systems loading CCR2-siRNA not only exerted pronounced anti-inflammatory effect through combining inhibit the chemotactic effect and ROS, but also effectively against ALI after blocking the circulatory effect of ROS and inflammatory cytokines. Therefore, this strategy of dual-driving force penetration mucus renders a unique approach for mediating trans-mucus nucleic acid delivery in lungs, and provide a promising treatment for the acute lung injury therapy.

Prevalence and risk factors of anxiety symptoms in first-episode and drug-naïve major depressive disorder patients with metabolic syndrome

Background and objectives Patients with major depressive disorder (MDD) have high comorbidity with metabolic syndrome (MetS), although anxiety is prevalent comorbidity in MDD patients. However, there is no study on anxiety symptoms (AS) in MDD patients with MetS. Therefore, we aimed to identify the prevalence and risk factors of AS in patients with MetS who experienced a first-episode and drug naïve (FEDN) of MDD. Methods In this cross-sectional study, 1718 FEDN of MDD outpatients with MetS were included. Sociodemographic data, clinical characteristics, suicidal attempts, and physical and biochemical parameters were collected. Hamilton Anxiety Rating Scale (HAMA), Hamilton Depression Rating Scale (HAMD), and Positive and Negative Syndrome Scale (PANSS) positive subscale were performed to detect the AS. Multiple linear regression analysis was used to analyze the correlation. Results The prevalence of AS in MDD patients with MetS was 85.96%, which was 1.79 times greater than that in patients with MDD alone (P<0.05). MDD patients with MetS had a greater rate of attempted suicide, a higher HAMD total score, and a higher diastolic blood pressure than MDD patients without AS (P<0.05). Their combination could distinguish AS in MDD patients. Moreover, HAMD score, thyroid-stimulating hormone (TSH) levels, PANSS positive score, and suicide attempts were related to HAMA scores in MDD patients with comorbid MetS (P<0.05). Conclusion There is a significant frequency of AS in MDD patients with MetS. Multiple clinical indicators and metabolic markers are associated with AS in patients with MDD and MetS. (AU)

Ir(IV) and Ir(III) in situ transition promotes ROS generation for eradicating multidrug-resistant bacterial infection.

Whether reactive oxygen species are a consequence or a cause of antibacterial activity is not fully known. A glutathione (GSH)-mediated oxidative defense mechanism is an important factor against bacterial infection. Reactive oxygen species (ROS) storm-mediated bacterial death by depleting GSH is also considered an effective strategy. Therefore, we designed and synthesized hybrid iridium ruthenium oxide nanozymes (IrRuOx NPs), where IrRuOx NPs alternately consume GSH through double redox electron pair auto-valent cycles, while an IrRuOx NP-mediated Fenton-like reaction occurs to realize an ROS storm, which in turn mediates lipid peroxidation to promote bacterial death. The results showed that IrRuOx NPs can effectively inhibit and kill Gram-positive and Gram-negative bacteria in vitro, and can be used as broad-spectrum antibiotics. Importantly, the wound and sepsis models of MRSA infection confirmed the efficient antibacterial activity of IrRuOx NPs in vivo. Accordingly, this study provides a new idea for metal oxide hybrid nanoenzymes and their biological functions.

Reactive oxygen species-mediated CuRuOX@HA hybrid nanozymes for multidrug-resistant bacterial infections with synergistic photothermal therapy.

Drug-resistant bacterial infections pose a serious threat to human life and health, especially multidrug-resistant bacterial infections are difficult to treat with currently available antibiotics. A number of evidences showed that reactive oxygen species (ROS) and photothermal therapy (PTT) can easily kill drug-resistant bacteria while they have not developed resistance to drugs. Inspired by good stability and high catalytic activity of nanozymes and in order to construct versatile nanozymes, the therapy of ROS was integrated with PTT. This study prepared a ROS-mediated copper-ruthenium oxide (CuRuOX) hybrid nanozyme (CuRuOX@HA) modified with hyaluronic acid (HA). Via hybridization, CuRuOX@HA NPs not only have good ROS generation capability but also possess excellent photothermal performance with a photothermal conversion efficiency of 62.7%. Thus, the CuRuOX@HA nanozyme achieves the synergistic treatment of drug-resistant bacterial infections using PTT/chemodynamic therapy (CDT). Moreover, under the mediated action of ROS, CuRuOX@HA can effectively deplete glutathione, which is a nutrient of bacteria, and hence, the nanozyme can impede the growth of drug-resistant bacteria. In vivo, this hybrid nanozyme efficiently removes MRSA from infected wounds and speeds up wound healing with few adverse effects. The CuRuOX@HA hybrid nanozyme is a viable candidate for clinical treatment due to its strong antibacterial activities and good biosafety.

Multifunctional Supramolecular Vesicles as Zn2+ -Triggered Microglial Modulator Alleviates Alzheimer's Disease.

Zn2+ -induced ß-amyloid protein (Aß) aggregation and microglia activation are the predominant contributors in Alzheimer's disease (AD). Regulating intracephalic excessive Zn2+ is a promising therapeutic strategy for AD treatment. However, only inhibition of Zn2+ is hardly to repair continuous damages caused by activated microglia. Herein, an intelligent resveratrol-loaded supramolecular vesicles (RES-loaded vesicles) with zinc ion chelation function and responsive release capability are constructed to alleviate Aß fibrillation, oxidative stress, and microglial dysfunction. The resveratrol encapsulation efficiency and drug loading efficiency are calculated to be 49.67% and 7.87%, respectively. In vitro studies demonstrate that the RES-loaded vesicles can modulate Zn2+ -dependent Aß aggregation. More importantly, the cargoes will be released in zinc environment and further reprograms microglia from proinflammatory M1 phenotype toward anti-inflammatory M2 phenotype, which prevents spontaneous neuroinflammation and alleviates cytotoxicity of cultured cells from 29% to 12%. With the stereotactic or intranasal administration, RES-loaded vesicles can overcome the blood brain barrier, alleviate neuronal apoptosis, neuroinflammation, and ultimately ameliorate cognitive impairment in two AD mouse models. This work provides a new sight for taking advantage of Zn2+ to treat CNS disorders.

Chiral Ruthenium Nanozymes with Self-Cascade Reaction Driven the NO Generation Induced Macrophage M1 Polarization Realizing the Lung Cancer "Cocktail Therapy".

Macrophages as the main cause of cancer immunosuppression, how to effectively induce macrophage M1 polarization remain the major challenge in lung cancer therapy. Herein, inspired by endogenous reactions, a strategy is proposed to coactivate macrophage M1 polarization by reactive oxygen species (ROS) and nitric oxide (NO) with self-autocatalytic cascade reaction. To enhance the generation of NO and ROS, NO Precursor-Arginine as capping agents for inducing synthesis two kinds of chiral ruthenium nanozyme (D/L-Arginine@Ru). Under the properties of Ru nanozymes through synchronously mimicking the activity of oxidase and nitric oxide synthase (NOS), chiral Ru nanozyme can rapidly generate 1 O2 and O2 at first stage, and then catalyze Arginine to produce sufficient NO, thus enhance macrophage M1 polarization to reverse tumor immunosuppression. Moreover, combination the antitumor activity of 1 O2 , NO, the chiral Ru nanozymes realize the "cocktail therapy" by inducing tumor cell apoptosis as well as ferroptosis. In addition, the chirality influences the bioactivity of Ru nanozymes that L-Arginine@Ru shows the better therapeutic effect with stronger catalytic activity and natural homology. It is hoped the high performance of chiral Ru nanozyme with "cocktail therapy" is an effective therapeutic reagent and can provide a feasible treatment strategy for tumor catalytic therapy.

Green Nanopesticide: pH-Responsive Eco-Friendly Pillar[5]arene-Modified Selenium Nanoparticles for Smart Delivery of Carbendazim to Suppress Sclerotinia Diseases.

Controlled-release delivery systems have been widely used to improve the efficacy and bioavailability of pesticides and minimize environmental risks. Herein, a fungicide carbendazim (CBZ)-loaded, a kind of nanovalve including trimethylammoniumpillar[5]arene (AP5), and methyl orange (MO)-functionalized mesoporous selenium (MSe) nanopesticides (CBZ@AP5/MSe⊃MO) were prepared. The nanovalve endowed CBZ@AP5/MSe⊃MO with a pH-responsive property, so the CBZ@AP5/MSe⊃MO can respond to the microenvironment of the pathogen Sclerotinia sclerotiorum (S. sclerotiorum). First, MO was shed due to protonation, and AP5-functionalized MSe gradually dissolved in an acid environment. Finally, CBZ was released rapidly. It is reported that AP5 and MO as the host and guest functionalized mesoporous selenium (MSe) have never been applied to agriculture. In vitro release experiments showed that the cumulative release rate of CBZ at pH 4.5 was 1.74 times higher than that in a neutral environment. In addition, we found that the contact angle of the CBZ@AP5/MSe⊃MO in maize and rape leaves was effectively decreased, which could retain more in the leaves after washout. It can also decrease the dry biomass and the reducing sugar of S.sclerotiorum. The CBZ@AP5/MSe⊃MO holds a good safety profile for plants, animal cells, and the environment owing to the targeted release properties. These results suggest that CBZ@AP5/MSe⊃MO is an environmentally friendly and effective drug-loaded system against S. sclerotiorum. It provides a new strategy for the design and development of nanopesticides and the control of S. sclerotiorum.

Macrophage Polarization Induced by Bacteria-Responsive Antibiotic-Loaded Nanozymes for Multidrug Resistance-Bacterial Infections Management.

Inherited bacterial resistance and biofilm-induced local immune inactivation are important factors in the failure of antibiotics to fight against bacterial infections. Herein, antibiotic-loaded mesoporous nanozymes (HA@MRuO2 -Cip/GOx) are fabricated for overcoming bacterial resistance, and activating the local immunosuppression in biofilm microenvironment (BME). HA@MRuO2 -Cip/GOx are prepared by physical adsorption between ciprofloxacin (Cip) or glucose oxidase (GOx) and MRuO2 NPs, and modified with hyaluronic acid (HA). In vitro, HA@MRuO2 -Cip/GOx cleaves extracellular DNA (eDNA) to disrupt biofilm, thereby enhancing Cip kill planktonic bacteria. Furthermore, HA@MRuO2 -Cip/GOx can induce polarization and enhance phagocytosis of a macrophage-derived cell line. More importantly, in vivo therapeutic performance confirms that HA@MRuO2 -Cip/GOx can trigger macrophage-related immunity, and effectively alleviate MRSA-bacterial lung infections. Accordingly, nanocatalytic therapy combined with targeted delivery of antibiotics could enhance the treatment of bacterial infections.

Ultrabroad Brillouin instantaneous frequency measurement with a designed linear system response.

We demonstrate an ultrabroad instantaneous frequency measurement (IFM) based on stimulated Brillouin scattering (SBS) with a designed linear system response. The linear system response is found to be the key factor that broadens the system bandwidth. It is realized by designing the sweeping method of frequency and amplitude of the local pump signal. With the improvement of linearity, the measurement error is decreased and the bandwidth of the SBS-based IFM is consequently enlarged. A Costas frequency modulated signal with an instantaneous bandwidth of 10.5 GHz is successfully measured by the designed system response. Further optimization of pump signal's characteristics extends the system bandwidth to 14.5 GHz. The measurement error of a linear frequency modulated (LFM) signal ranging from 6 GHz to 20.5 GHz is less than 1% of the instantaneous bandwidth.

Enhancement of time-delay measurement accuracy of an insufficient stimulated Brillouin scattering based pulse compression system via lock-in detection.

We demonstrate a novel scheme to increase the accuracy of time-delay measurement of an insufficient stimulated Brillouin scattering (ISBS) based pulse compression system. It is realized by relating the time delay with the pulse compression gain, which is accumulated by a lock-in amplifier (LIA). We theoretically demonstrate that the time delay is proportional to the accumulated gain via the LIA. In the experiment, the pulse compression gain is accumulated through lock-in detection. It narrows down the detection bandwidth and reduces the influence from the broadband noise. The time-delay measurement is completed in a real-time manner and thus provides a possible solution to realizing a high-speed process in the future. The accuracy of measurement of a linear frequency modulated (LFM) signal with a bandwidth of 1 GHz is 1 ns.

Silver Nanowire Ink for Flexible Circuit on Textiles.

Low cost electronics implemented in textiles could pave the way to a fully new generation of smart products in the fields of healthcare, sport, fashion, and safety. Although many methods have found their way into the market, many problems still need to be solved and much progress has to be made to enable the commercial exploitation of such products. In this paper, silver nanowires of 60⁻100 nm in diameter and 8⁻15 µm in length were achieved by the polyol solvothermal method, and aqueous silver nanowire conductive inks were prepared with the synthesized silver nanowires as the conductive phase, in the presence of polyaniline, guar, and hydrochloric acid. The conductive inks were printed on cotton fabric substrate by screen printing process. The effects of the amount of silver nanowires, layers of coating, and treatment temperature on the microstructure and electrical properties of samples were investigated by scanning electron microscopy and the four-point probe method. The results show that the conductivity and densification of the samples increased with increased amount of silver nanowires, layers of coating, and treatment temperature. The heat treatment helped to improve densification of the silver nanowires and conductivity of the sample. The resistance of the samples increased after bending due to loosening of the overlap between the silver nanowires.

Comparative in vivo antioxidant capacity of DL-2-hydroxy-4-methylthiobutanoic acid (HMTBA) and DL-methionine in male mice fed a high-fat diet.

BACKGROUND: In animal diets, methionine (Met) is considered to be the first limiting amino acid, and the activity of synthetic Met is typically added either as DL-methionine (DLM) or as DL-2-hydroxy-4-methylthiobutanoic acid (HMTBA). It has been demonstrated that HMTBA exhibits a higher antioxidant capability in vitro as compared to DLM. However, the difference in antioxidant capability between DLM and HMTBA in vivo is unknown. METHODS: In the present study, 60 male C57BL/6 mice were randomly divided into six groups and fed either a normal diet (NFD, 5.37% fat) or a high-fat diet (HFD, 19.7% fat) in conjunction with 0.2% DLM, 0.2% HMTBA or 0.1% DLM and 0.1% HMTBA for 4 weeks. RESULTS: HFD supplemented with 2% DLM and NFD with 2% HMTBA both induced adverse affects in relation to serum lipid parameters and depressed antioxidant defense systems in the digestive system. However, these changes were restored in the 0.2% HMTBA-treated HFD group. Furthermore, no significant differences were found in the lipid parameters and antioxidant status in the NFD and HFD group supplemented with 0.1% DLM and 0.1% HMTBA. CONCLUSION: HMTBA restored oxidative redox status under OS conditions and its antioxidant properties were positively correlated with the dosage included in diet.