Fluorinated Hafnium and Zirconium Coenable the Tunable Biodegradability of Core-Multishell Heterogeneous Nanocrystals for Bioimaging.

Upconversion (UC)/downconversion (DC)-luminescent lanthanide-doped nanocrystals (LDNCs) with near-infrared (NIR, 650-1700 nm) excitation have been gaining increasing popularity in bioimaging. However, conventional NIR-excited LDNCs cannot be degraded and eliminated eventually in vivo owing to intrinsic "rigid" lattices, thus constraining clinical applications. A biodegradability-tunable heterogeneous core-shell-shell luminescent LDNC of Na3HfF7:Yb,Er@Na3ZrF7:Yb,Er@CaF2:Yb,Zr (abbreviated as HZC) was developed and modified with oxidized sodium alginate (OSA) for multimode bioimaging. The dynamic "soft" lattice-Na3Hf(Zr)F7 host and the varying Zr4+ doping content in the outmoster CaF2 shell endowed HZC with tunable degradability. Through elaborated core-shell-shell coating, Yb3+/Er3+-coupled UC red and green and DC second near-infrared (NIR-II) emissions were, respectively, enhanced by 31.23-, 150.60-, and 19.42-fold when compared with core nanocrystals. HZC generated computed tomography (CT) imaging contrast effects, thus enabling NIR-II/CT/UC trimodal imaging. OSA modification not only ensured the exemplary biocompatibility of HZC but also enabled tumor-specific diagnosis. The findings would benefit the clinical imaging translation of LDNCs.

Efficacy of washed microbiota transplantation for therapeutic targets of refractory functional constipation and the influencing factors: a single-center, retrospective, 24-week follow-up study.

BACKGROUND: The efficacy of washed microbiota transplantation (WMT) in terms of refractory functional constipation (FC)-related therapeutic targets and influencing factors have not been elucidated. This study aimed to assess the efficacy and influencing factors of WMT in treating refractory FC-related therapeutic targets. METHODS: The clinical data of patients diagnosed with refractory FC and received with WMT were retrospectively collected. The therapeutic targets included straining, hard stools, incomplete evacuation, a sense of anorectal obstruction, manual maneuvers, and decreased stool frequency. Each target was recorded as 1 (yes) or 0 (no). All patients were followed up for approximately 24 weeks from the end of the first course of WMT. The primary outcomes were the improvement rates for the individual therapeutic targets and the overall response in respect of the therapeutic targets decreased by 2 at weeks 4, 8, and 24. The secondary outcomes were the clinical remission rate (i.e., the proportion of patients with an average of 3 or more spontaneous complete bowel movements per week), clinical improvement rate (i.e., the proportion of patients with an average increase of 1 or more SCBMs/week or patients with remission), stool frequency, Wexner constipation score, Bristol Stool Form Scale (BSFS) score, and adverse events. The factors influencing the efficacy were also analyzed. RESULTS: Overall, 63 patients with 112 WMT courses were enrolled. The improvement rates at weeks 8 and 24 were 45.6% and 35.0%, 42.9% and 38.6%, 45.0% and 35.7%, 55.6% and 44.4%, and 60.9% and 50.0%, respectively, for straining, hard stools, incomplete evacuation, a sense of anorectal obstruction, and decreased stool frequency. The overall response rates were 49.2%, 50.8%, and 42.9%, respectively, at weeks 4, 8, and 24. The rates of clinical remission and clinical improvement were 54.0% and 68.3%, respectively, at weeks 4. The stool frequency, BSFS score, and Wexner constipation score tended to improve post-WMT. Only 22 mild adverse events were observed during the 112 WMT courses and the follow-up. The number of WMT courses was identified to be the independent factor influencing the efficacy. CONCLUSIONS: WMT is efficacious in improving refractory FC-related therapeutic targets. The effectiveness of WMT in the management of FC is enhanced with the administration of multiple courses.

Intelligent Fe-Mn Layered Double Hydroxides Nanosheets Anchored with Upconversion Nanoparticles for Oxygen-Elevated Synergetic Therapy and Bioimaging.

Multimodal synergistic therapy based on photodynamic therapy (PDT), photothermal therapy (PTT), and chemodynamic therapy (CDT) has attracted increasing attention in cancer therapy. However, the scant therapeutic efficiency is always a barrier for further application. Herein, a smart tumor microenvironment (TME) responsive nanocatalysts are developed by adopting Fe-Mn layered double hydroxides (FeMn-LDH) as an effective photothermal nanocarrier to load mesoporous silica and chlorin e6 (Ce6)-covalently coated upconversion nanoparticles (UCSP) for multimodal imaging for directed therapy. Under acidic TME, FeMn-LDH degrades into Fe3+ and Mn2+ ions to initiate a Fenton-like reaction inducing CDT and enhancing magnetic resonance imaging. Additionally, Fe3+ can decompose H2 O2 to oxygen (O2 ), enhancing PDT guided by UCSP. As a representative noninvasive imaging probe, the upconversion luminescence will recover after decomposition of FeMn-LDH, and provide high-resolution upconversion luminescent imaging guidance for pinpointed PDT. Moreover, the photothermal properties of FeMn-LDH can further enhance CDT effects. The synergistic therapy and multifunctional imaging can realize the integration of diagnosis and treatment.

Glutathione Mediated Size-Tunable UCNPs-Pt(IV)-ZnFe2 O4 Nanocomposite for Multiple Bioimaging Guided Synergetic Therapy.

Here a multifunctional nanoplatform (upconversion nanoparticles (UCNPs)-platinum(IV) (Pt(IV))-ZnFe2 O4 , denoted as UCPZ) is designed for collaborative cancer treatment, including photodynamic therapy (PDT), chemotherapy, and Fenton reaction. In the system, the UCNPs triggered by near-infrared light can convert low energy photons to high energy ones, which act as the UV-vis source to simultaneously mediate the PDT effect and Fenton's reaction of ZnFe2 O4 nanoparticles. Meanwhile, the Pt(IV) prodrugs can be reduced to high virulent Pt(II) by glutathione in the cancer cells, which can bond to DNA and inhibit the copy of DNA. The synergistic therapeutic effect is verified in vitro and in vivo results. The cleavage of Pt(IV) from UCNPs during the reduction process can shift the larger UCPZ nanoparticles (NPs) to the smaller ones, which promotes the enhanced permeability and retention (EPR) and deep tumor penetration. In addition, due to the inherent upconversion luminescence (UCL) and the doped Yb3+ and Fe3+ in UCPZ, this system can serve as a multimodality bioimaging contrast agent, covering UCL, X-ray computed tomography, magnetic resonance imaging, and photoacoustic. A smart all-in-one imaging-guided diagnosis and treatment system is realized, which should have a potential value in the treatment of tumor.

Quad-Model Imaging-Guided High-Efficiency Phototherapy Based on Upconversion Nanoparticles and ZnFe2O4 Integrated Graphene Oxide.

The strategy of diagnosis-to-therapy to realize the integration of imaging and high antitumor efficiency has become the most promising method. Light-induced therapeutic technologies have drawn considerable interest. However, the limited penetration depth of UV/vis excitation and relatively low efficiency are the main obstacles for its further clinic application. For this concern, we presented a facile method to anchor ultrasmall ZnFe2O4 nanoparticles and upconversion luminescence nanoparticles (UCNPs) on graphene oxide (GO) nanosheets (GO/ZnFe2O4/UCNPs, abbreviated as GZUC). To solve the penetration question, here we introduced Tm3+-doped UCNPs to convert the high-penetrated near-infrared (NIR) light into UV/vis photons to activate the photodynamic process. In this system, the dual phototherapy from GO and ZnFe2O4 has been realized upon NIR laser irradiation. Combined with the photodynamic therapy (PDT) based on Fenton reaction that ZnFe2O4 nanoparticles react with excessive H2O2 in tumor microenvironment to produce toxic hydroxyl radicals (·OH), an excellent anticancer efficiency has been achieved. Furthermore, 4-fold imaging including upconversion luminescence (UCL), computed tomography (CT), magnetic resonance imaging (MRI) and photoacoustic tomography (PAT) has been obtained due to its intrinsic properties, thereby successfully realizing diagnosis-monitored therapy. Our demonstration provided a feasible strategy to solve the main problems in current light-triggered theranostic.

Integration of IR-808 Sensitized Upconversion Nanostructure and MoS2 Nanosheet for 808 nm NIR Light Triggered Phototherapy and Bioimaging.

Near infrared (NIR) light triggered phototherapy including photothermal therapy (PTT) and photodynamic therapy (PDT) affords superior outcome in cancer treatment. However, the reactive oxygen species (ROS) generated by NIR-excited upconversion nanostructure is limited by the feeble upconverted light which cannot activate PDT agents efficiently. Here, an IR-808 dye sensitized upconversion nanoparticle (UCNP) with a chlorin e6 (Ce6)-functionalized silica layer is developed for PDT agent. The two booster effectors (dye-sensitization and core-shell enhancement) synergistically amplify the upconversion efficiency, therefore achieving superbright visible emission under low 808 nm light excitation. The markedly amplified red light subsequently triggers the photosensitizer (Ce6) to produce large amount of ROS for efficient PDT. After the silica is endowed with positive surface, these PDT nanoparticles can be easily grafted on MoS2 nanosheet. As the optimal laser wavelength of UCNPs is consistent with that of MoS2 nanosheet for PTT, the invented nanoplatform generates both abundant ROS and local hyperthermia upon a single 808 nm laser irradiation. Both the in vitro and in vivo assays validate that the innovated nanostructure presents excellent cancer cell inhibition effectiveness by taking advantages of the synergistic PTT and PDT, simultaneously, posing trimodal (upconversion luminescence/computed tomography (CT)/magnetic resonance imaging (MRI) imaging capability.

Washed Microbiota Transplantation Is Associated With Improved Lipid Profiles: Long-Term Efficacy and Safety in an Observational Cohort From South China.

INTRODUCTION: Dyslipidemia is one of the main risk factors of chronic metabolic diseases. Our previous studies have shown that washed microbiota transplantation (WMT) has a significant improvement effect on patients with hyperlipidemia and hypolipemia in the Chinese population. The purpose of this study was to further explore the long-term efficacy and safety of WMT in patients with hyperlipidemia. METHODS: Clinical data of patients who received WMT for multicourse were collected. Changes of blood lipid indexes before and after WMT, including triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), lipoprotein A, and Apolipoprotein B. RESULTS: A total of 124 patients were enrolled, including 56 cases in the hyperlipidemia group and 68 cases with normal lipids. The mean observation time was 787.80 ± 371.45 days, and the longest follow-up time was 1,534 days. TC and non-HDL-C in the hyperlipidemia group with 1-4 courses of WMT were significantly reduced ( P < 0.05); TG decreased significantly after the second course ( P < 0.05); low-density lipoprotein cholesterol also significantly decreased after the fourth course of treatment ( P < 0.05); TG, TC, and non-HDL-C significantly decreased in single course, double course, and multiple course, respectively ( P < 0.05). In terms of time period, over 1 year, the improvement in multicourse treatment was more significant than the single and double-course ones. In terms of comprehensive efficacy, WMT restored 32.14% of patients in the hyperlipidemia group to the normal lipid group ( P < 0.001), of which 30.00% recovered to the normal lipid group within 1 year ( P = 0.004) and 65.38% were reassigned to the normal lipid group over 1 year ( P = 0.003). In addition, over the 1-year treatment period, WMT significantly degraded the high-risk and medium-risk groups of atherosclerotic cardiovascular disease risk stratification in hyperlipidemia cases. There were no serious adverse events. DISCUSSION: WMT had a long-term improvement effect on patients with hyperlipidemia. The effect of multiple courses over 1 year was more significant than that of single/double courses and also had a significant destratification effect on the risk of atherosclerotic cardiovascular disease with high safety. Therefore, WMT provides a safe and long-term effective clinical treatment for patients with dyslipidemia.

Gallic acid-loaded HFZIF-8 for tumor-targeted delivery and thermal-catalytic therapy.

"Transition" metal-coordinated plant polyphenols are a type of promising antitumor nanodrugs owing to their high biosafety and catalytic therapy potency; however, the major obstacle restricting their clinical application is their poor tumor accumulation. Herein, Fe-doped ZIF-8 was tailored using tannic acid (TA) into a hollow mesoporous nanocarrier for gallic acid (GA) loading. After hyaluronic acid (HA) modification, the developed nanosystem of HFZIF-8/GA@HA was used for the targeted delivery of Fe ions and GA, thereby intratumorally achieving the synthesis of an Fe-GA coordinated complex. The TA-etching strategy facilitated the development of a cavitary structure and abundant coordination sites of ZIF-8, thus ensuring an ideal loading efficacy of GA (23.4 wt%). When HFZIF-8/GA@HA accumulates in the tumor microenvironment (TME), the framework is broken due to the competitive protonation ability of overexpressed protons in the TME. Interestingly, the intratumoral degradation of HFZIF-8/GA@HA provides the opportunity for the in situ "meeting" of GA and Fe ions, and through the coordination of polyhydroxyls assisted by conjugated electrons on the benzene ring, highly stable Fe-GA nanochelates are formed. Significantly, owing to the electron delocalization effect of GA, intratumorally coordinated Fe-GA could efficiently absorb second near-infrared (NIR-II, 1064 nm) laser irradiation and transfer it into thermal energy with a conversion efficiency of 36.7%. The photothermal performance could speed up the Fenton reaction rate of Fe-GA with endogenous H2O2 for generating more hydroxyl radicals, thus realizing thermally enhanced chemodynamic therapy. Overall, our research findings demonstrate that HFZIF-8/GA@HA has potential as a safe and efficient anticancer nanodrug.

Optimized silicate nanozymes with atomically incorporated iron and manganese for intratumoral coordination-enhanced once-for-all catalytic therapy.

Although plant-derived cancer therapeutic products possess great promise in clinical translations, they still suffer from quick degradation and low targeting rates. Herein, based on the oxygen vacancy (OV)-immobilization strategy, an OV-enriched biodegradable silicate nanoplatform with atomically dispersed Fe/Mn active species and polyethylene glycol modification was innovated for loading gallic acid (GA) (noted as FMMPG) for intratumoral coordination-enhanced multicatalytic cancer therapy. The OV-enriched FMMPG nanozymes with a narrow band gap (1.74 eV) can be excited by a 650 nm laser to generate reactive oxygen species. Benefiting from the Mn-O bond in response to the tumor microenvironment (TME), the silicate skeleton in FMMPG collapses and completely degrades after 24 h. The degraded metal M (M = Fe, Mn) ions and released GA can in situ produce a stable M-GA nanocomplex at tumor sites. Importantly, the formed M-GA with strong reductive ability can transform H2O2 into the fatal hydroxyl radical, causing serious oxidative damage to the tumor. The released Fe3+ and Mn2+ can serve as enhanced contrast agents for magnetic resonance imaging, which can track the chemodynamic and photodynamic therapy processes. The work offers a reasonable strategy for a TME-responsive degradation and intratumoral coordination-enhanced multicatalytic therapy founded on bimetallic silicate nanozymes to achieve desirable tumor theranostic outcomes.

Targeted Delivery of Active Sites by Oxygen Vacancy-Engineered Bimetal Silicate Nanozymes for Intratumoral Aggregation-Potentiated Catalytic Therapy.

Biodegradable silicate nanoconstructs have aroused tremendous interest in cancer therapeutics due to their variable framework composition and versatile functions. Nevertheless, low intratumoral retention still limits their practical application. In this study, oxygen vacancy (OV)-enriched bimetallic silicate nanozymes with Fe-Ca dual active sites via modification of oxidized sodium alginate and gallic acid (GA) loading (OFeCaSA-V@GA) were developed for targeted aggregation-potentiated therapy. The band gap of silica markedly decreased from 2.76 to 1.81 eV by codoping of Fe3+ and Ca2+, enabling its excitation by a 650 nm laser to generate reactive oxygen species. The OV that occurred in the hydrothermal synthetic stage of OFeCaSA-V@GA can anchor the metal ions to form an atomic phase, offering a massive fabrication method of single-atom nanozymes. Density functional theory results reveal that the Ca sites can promote the adsorption of H2O2, and Fe sites can accelerate the dissociation of H2O2, thereby realizing a synergetic catalytic effect. More importantly, the targeted delivery of metal ions can induce a morphological transformation at tumor sites, leading to high retention (the highest retention rate is 36.3%) of theranostic components in tumor cells. Thus, this finding may offer an ingenious protocol for designing and engineering highly efficient and long-retention nanodrugs.

Embedding Atomically Dispersed Manganese/Gadolinium Dual Sites in Oxygen Vacancy-Enriched Biodegradable Bimetallic Silicate Nanoplatform for Potentiating Catalytic Therapy.

Due to their atomically dispersed active centers, single-atom nanozymes (SAzymes) have unparalleled advantages in cancer catalytic therapy. Here, loaded with chlorin e6 (Ce6), a hydrothermally mass-produced bimetallic silicate-based nanoplatforms with atomically dispersed manganese/gadolinium (Mn/Gd) dual sites and oxygen vacancies (OVs) (PMnSA GMSNs-V@Ce6) is constructed for tumor glutathione (GSH)-triggered chemodynamic therapy (CDT) and O2 -alleviated photodynamic therapy. The band gaps of silica are significantly reduced from 2.78 to 1.88 eV by doping with metal ions, which enables it to be excited by a 650 nm laser to produce electron-hole pairs, thereby facilitating the generation of reactive oxygen species. The Gd sites can modulate the local electrons of the atom-catalyzed Mn sites, which contribute to the generation of superoxide and hydroxyl radicals (• OH). Tumor GSH-triggered Mn2+ release can convert endogenous H2 O2 to • OH and realize GSH-depletion-enhanced CDT. Significantly, the hydrothermally generated OVs can not only capture Mn and Gd atoms to form atomic sites but also can elongate and weaken the O-O bonds of H2 O2 , thereby improving the efficacy of Fenton reactions. The degraded Mn2+ /Gd3+ ions can be used as tumor-specific magnetic resonance imaging contrast agents. All the experimental results demonstrate the great potential of PMnSA GMSNs-V@Ce6 as cancer theranostic agent.

Comparison of the use of a spiral nasojejunal tube and transendoscopic enteral tubing in washed microbiota transplantation via the mid-gut route.

Background: Methods for washed microbiota transplantation (WMT) through the mid-gut include transendoscopic enteral tubing (TET) and manual spiral nasojejunal tube (SNT) placement have not been studied. Methods: This prospective interventional study was performed at a single centre. Patients were divided into the SNT and mid-gut TET groups based on their conditions and wishes. In the SNT group, an SNT was passively inserted into the stomach, and abdominal X-rays were taken within 24 h to confirm tube placement in the small intestine. In the mid-gut TET group, mid-gut TET was placed in the small intestine for gastroscopy. Data on the clinical efficacy of WMT, intubation time, cost, overall comfort score, adverse reactions, etc., were collected from the two groups. Results: Sixty-three patients were included in the study (SNT group (n = 40) and mid-gut TET group (n = 23)). The clinical efficacy of WMT in the SNT and mid-gut TET groups was 90 % and 95.7 %, respectively (P = 0.644). Compared with the mid-gut TET group, the SNT group showed a shorter operation time (120 s vs. 258 s, P = 0.001) and a lower average cost (641.7 yuan vs. 1702.1 yuan, P = 0.001). There was no significant difference in the overall comfort score or the incidence of common discomfort symptoms between the two groups. Conclusion: The different implantation methods have different advantages; compared with mid-gut TET placement, manual SNT placement provides some benefits.

Protective effect and mechanism of Qingfei Paidu decoction on myocardial damage mediated by influenza viruses.

Introduction: Significant attention has been paid to myocardial damage mediated by the single-stranded RNA virus. Qingfei Paidu decoction (QFPDD) has been proved to protect the damage caused by the influenza virus A/PR/8/1934 (PR8), but its specific mechanism is unclear. Methods: Molecular biological methods, together with network pharmacology, were used to analyze the effects and underlying mechanism of QFPDD treatment on PR8-induced myocardial damage to obtain insights into the treatment of COVID-19-mediated myocardial damage. Results: Increased apoptosis and subcellular damage were observed in myocardial cells of mice infected by PR8. QFPDD treatment significantly inhibited the apoptosis and subcellular damage induced by the PR8 virus. The inflammatory factors IFN-ß, TNF-α, and IL-18 were statistically increased in the myocardia of the mice infected by PR8, and the increase in inflammatory factors was prevented by QFPDD treatment. Furthermore, the expression levels or phosphorylation of necroptosis-related proteins RIPK1, RIPK3, and MLKL were abnormally elevated in the group of infected mice, while QFPDD restored the levels or phosphorylation of these proteins. Our study demonstrated that HIF-1α is a key target of QFPDD in the treatment of influenza virus-mediated injury. The HIF-α level was significantly increased by PR8 infection. Both the knockdown of HIF-1α and treatment of the myocardial cell with QFPDD significantly reversed the increased inflammatory factors during infection. Overexpression of HIF-1α reversed the inhibition effects of QFPDD on cytokine expression. Meanwhile, seven compounds from QFPDD may target HIF-1α. Conclusion: QFPDD can ameliorate influenza virus-mediated myocardial damage by reducing the degree of cell necroptosis and apoptosis, inhibiting inflammatory response and the expression of HIF-1α. Thus, our results provide new insights into the treatment of respiratory virus-mediated myocardial damage.

The association between short-term exposure to nitrogen dioxide and hospital admission for schizophrenia: A systematic review and meta-analysis.

BACKGROUND: Ambient air pollution has been identified as a primary risk factor for mental disorders. In recent years, the relationship between exposure to ambient nitrogen dioxide (NO2) and the risk of hospital admissions (HAs) for schizophrenia has garnered increasing scientific interest, but evidence from epidemiological studies has been inconsistent. Therefore, a systematic review and meta-analysis were conducted to comprehensively identify potential correlations. METHODS: A literature search in 3 international databases was conducted before December 31, 2022. Relative risk (RR) and corresponding 95% confidence intervals (CI) were calculated to evaluate the strength of the associations. Summary effect sizes were calculated using a random-effects model due to the expected heterogeneity (I2 over 50%). RESULTS: A total of ten eligible studies were included in the meta-analysis, including 1,412,860 participants. The pooled analysis found that an increased risk of HAs for schizophrenia was associated with exposure to each increase of 10 µg/m3 in NO2 (RR = 1.029, 95% CI = 1.016-1.041, P < .001). However, the heterogeneity was high for the summary estimates, reducing the credibility of the evidence. In 2-pollutant models, results for NO2 increased by 0.3%, 0.2% and 2.3%, respectively, after adjusting for PM2.5, PM10 and SO2. CONCLUSIONS: This study provides evidence that NO2 exposure significantly increases the risk of hospital admission for schizophrenia. Future studies are required to clarify the potential biological mechanism between schizophrenia and NO2 exposure to provide a more definitive result.

Green Synthesis and Antimicrobial Study on Functionalized Chestnut-Shell-Extract Ag Nanoparticles.

The chestnut shell is usually discarded as agricultural waste and the random deposition of it can cause environmental problems. In this study, monodisperse crystalline Ag nanoparticles (AgNPs) were synthesized by a hydrothermal approach, in which the chestnut shell extract served as both reducing agent and stabilizer. The synthesized Ag nanoparticles were characterized by ultraviolet-visible (UV) spectrophotometry, transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD) measurements. The TEM, XRD and XPS results revealed that the synthesized product was spherical Ag nanoparticles with a face-centered cubic crystal structure. The antimicrobial activity test indicated that the Ag nanoparticles modified by the chestnut shell extract had an obvious inhibitory effect on Escherichia coli, Staphylococcus aureus and Candida albicans. The measured MIC and MBC of functionalized chestnut-shell-extract AgNPs against E. coli, S. aureus and C. albicans is relatively low, which indicated that the present functionalized chestnut-shell-extract AgNPs are an efficient antimicrobial agent.

Metal-polyphenol network coated magnetic hydroxyapatite for pH-activated MR imaging and drug delivery.

Engineered nanoparticles responsive to tumor microenvironment parameters such as pH have been developed as drug carriers and for magnetic resonance imaging (MRI) as contrast agents (CA). Nanoscale hydroxyapatite (HAP) has good biocompatibility and specific inhibition of tumor cells. However, the inherent tendency of nanoscale HAP to agglomerate and degrade under natural conditions has hindered its further application. To address this challenge, polyacrylic acid-coordinated Mn2+ and F- co-doped nanoscale HAP (MnxFHA-PAA) were developed for MRI and doxorubicin (DOX) loading. Moreover, the metal-polyphenol network (MPN) formed by ligating tannic acid (TA) and Fe3+ was successfully functionalized onto the surface of MnxFHA-PAA-DOX. The pH-sensitive MPN improves biocompatibility and therapeutic efficacy while preventing the premature release of DOX in a neutral environment. It was demonstrated that the mesoporous structure of MnxFHA-PAA@TA-Fe nanoparticles with good dispersion, high specific surface area and large pore size, which can reach more than 90 % encapsulation efficiency (EE) for DOX. MnxFHA-PAA-DOX@TA-Fe degrades at low pH and releases Mn2+ and DOX that are confined in the nanoparticles. Binding of Mn2+ to proteins leads to increased relaxation and enhanced MRI contrast. Such nanoparticles with sensitive pH responsiveness have great potential for tumor diagnosis and therapeutic synergy.

Effects of varenicline on the serum levels of olanzapine in male patients with Schizophrenia: a randomized controlled trial.

Background: Smoking in patients with Schizophrenia is more common than in the general population. Varenicline, a partial agonist at α4ß2 nicotinic acetylcholine receptors, is an effective smoking cessation pharmacotherapy in patients with Schizophrenia. However, its effects on the serum levels of antipsychotics in Schizophrenia are understudied. This study investigated the impact of smoking cessation with varenicline on the serum concentration of olanzapine in patients with Schizophrenia. Methods: Adult smokers with Schizophrenia were enrolled in a 12-week course of varenicline and placebo for smoking cessation. The serum concentration of olanzapine was measured at baseline and weeks 1, 2, 4, 8, and 12. Data were analyzed with the generalized additive mixed model. Results: During the 12-week study, the results indicated that olanzapine concentrations increased nonlinearly in the varenicline and placebo groups. Threshold effect analysis suggested that the olanzapine concentrations increased over time until the turning point (week 4). However, there was no significant difference between the two treatment groups. Conclusion: Varenicline showed safety and efficacy in smoking cessation in people with Schizophrenia.

Optimized core-shell lanthanide nanoparticles with ultrabright Ce3+-modulated second near-infrared emission for "lighting" plants.

Second near-infrared (NIR-II, 1000-1700 nm) photon-mediated fluorescence imaging has attracted extensive interest in the field of bioimaging. However, NIR-II fluorescent nanoprobes competent for plant imaging have been rarely developed. Herein, lanthanide-doped nanoparticle (LDNP) optimal core-shell structure and ultrabright NIR-II emission were developed for "lighting" plants. The Ce3+-doped active shell coated on the NaErF4:Tm core enables dual-mode red upconversion (UC) and NIR-II downconversion (DC) emission of LDNPs upon 980 nm laser excitation. Under the optimized doping content, the intensities of red UC and NIR-II DC emission were respectively boosted by 5- and 19-fold those of the core nanoparticles, which endowed LDNPs with ideal NIR-II emissive capabilities for optical imaging of plants. Significantly, the NIR-II fluorescent signal affords much higher signal-to-noise rate than the red UC. LDNPs were modified with polyethyleneimine to enable outstanding hydrophilicty and facilitate their uptake by plants. Arabidopsis thaliana and Nicotiana benthamiana were chosen as plant models for NIR-II imaging studies. The toxic effect of LDNPs after being transported into Brassica rapa chinensis was systematically studied on mice. The NIR-II imaging strategy offers a promising method for studying the uptake and transport of nanoparticles in plants.

Gut microbiota from essential tremor patients aggravates tremors in mice.

Background and objective: Essential tremor (ET) lacks effective treatments because its underlying mechanism is largely unknown, but may involve gut microbiota via the microbiome-gut-brain axis. We explored the effects of gut microbiota on ET in mice. Methods: Specific pathogen-free C57BL/6J mice were gavaged with stools from ET patients or matched healthy individuals. After 3 weeks of gavaging, behavioral tests were performed on all mice. Next, each mouse was injected with harmaline to induce tremors. The tremor duration was recorded; the tremor score was estimated every 30 min. Behavioral tests were repeated after modeling. Intestinal tissues and fecal samples of the mice were examined using histology and 16Sr DNA sequencing, respectively. Results: Compared with mice receiving microbiota from healthy controls, mice receiving fecal suspensions from ET patients showed worse performance in the pre-modeling behavioral tests. After modeling, ET-group mice showed significantly greater tremor scores, longer tremor duration, and worse motor performance. They also had significantly lower body weight and lower fecal pellet count. Pathological scoring revealed more severe intestinal lesions in ET-group mice. The 16S rDNA sequencing data revealed significant differences in microbiota indices, and a correlation between these indices and tremors in mice. Functional predictions indicated that the abundance of GABA-related enzymes was altered in ET-group mice. Conclusion: Mice transplanted with gut microbiota from ET patients showed worse performance in behavioral tests. After modeling, ET-group mice presented longer tremor duration, higher tremor score, and worse motor performance. This study provides evidence for gut microbiota dysbiosis that may affect the pathogenesis of ET.

Washed Microbiota Transplantation Improves Patients with Overweight by the Gut Microbiota and Sphingolipid Metabolism.

BACKGROUND: Overweight (OW) and obesity have become increasingly serious public health problems worldwide. The clinical impact of washed microbiota transplantation (WMT) from healthy donors in OW patients is unclear. This study aimed to investigate the effect of WMT in OW patients. METHODS: The changes in body mass index (BMI = weight (kg)/height (m)2), blood glucose, blood lipids and other indicators before and after WMT were compared. At the same time, 16S rRNA gene amplicon sequencing was performed on fecal samples of OW patients before and after transplantation. Finally, serum samples were tested for sphingolipids targeted by lipid metabolomics. RESULTS: A total of 166 patients were included, including 52 in the OW group and 114 in the normal weight (NOW) group. For OW patients, WMT significantly improved the comprehensive efficacy of OW. In the short term (about 1 month) and medium term (about 2 months), a significant reduction in BMI was seen. At the same time, in the short term (about 1 month), liver fat attenuation (LFA), triglyceride (TG) and fasting blood glucose (FBG) were significantly reduced. In the long term (about 5 months), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), non-high-density lipoprotein (non-HDL-c), etc. were significantly reduced. WMT improved the gut microbiota of OW patients, and also had an improvement effect on OW patients by regulating sphingolipid metabolism. CONCLUSION: WMT had a significant improvement effect on OW patients. WMT could restore gut microbiota homeostasis and improve OW patients by regulating sphingolipid metabolism.