Effect of Gushen shetuo decoction in improving motor and non-motor symptoms and the expression of PERK, ATF4 and CHOP in patients with Parkinson's disease.

This study aims to observe the therapeutic effect of Gushen Shetuo decoction on Parkinson's disease (PD), so as to provide reference for clinical practice. In order to demonstrate the clinical value of Gushen Shetuo Decoction, we selected 80 patients with PD for the study. Among them, 38 patients received the Gushen Shetuo decoction (research group), and 42 patients received Levodopa and Benserazide Hydrochloride Tablets (control group). There was no difference in Non-Motor Symptoms Scale (NMSS) scores between the research group and the control group (P>0. 05). However, the scores of motor complications in Movement Disorder Society-sponsored revision of the Parkinson's Disease Rating Scale (MDS-UPDRS) and those of Drooling Severity and Frequency Scale (DSFS) in the research group were lower than those in the control group (P<0. 05). Subsequently, we established PD model rats, and after Gushen Shetuo Decoction gavage treatment, we found that rats in the intervention group had increased mobility (P<0. 05), as well as notably improved pathological damage of substantia nigra and striatum. Also, the expression of PERK, ATF4 and CHOP in the brain tissues of rats in the intervention group was lower than those in the control group (P<0. 05). These results confirm that Gushen Shetuo decoction effectively improved the drooling of patients with PD and showed high safety.

Geochemical behaviors of uranium and thorium during weathering and pedogenesis of carbonate rock: constraint from their speciation.

During weathering and pedogenesis of carbonate rock with poor-uranium (U) and thorium (Th), U and Th present the characteristics of strong leaching (especially U) and significant residual enrichment, the cause of which is still unclear. In this paper, a weathering profile developed by dolomite in karst area of Guizhou province in southwest China was selected, which showed zonation characteristics of bedrock (Y), powdery rock (Yf), and soil layer (T1 to T12) from the bottom to up. Through the determination of the occurrence speciation of U and Th in Y and weathering profile, combined with mineralogical, geochemical characteristics, and element mass balance calculation, the constraints of U and Th speciation on the geochemical behavior of U and Th during the weathering of carbonate rock were revealed. The results proved that U and Th in Y preferentially existed in acid insoluble phase, for example, the contents of U and Th in Y were 0.90 mg·kg-1 and 0.28 mg·kg-1, respectively, while those in acid insoluble matter were 2.34 mg·kg-1 and 2.57 mg·kg-1, respectively, but because the mass percentage of acid insoluble matter was extremely low (0.95%), the mass percentages of U and Th in the acid soluble phase in the whole rock were absolutely superior (96% of U and 86% Th). The U and Th in the acid soluble phase of Y were mainly adsorbed on the crystal surface of carbonate minerals or existed in the cement, and the U and Th in the carbonate lattice only accounted for a small proportion. From Y to Yf with the initial dissolution, U and Th released from the surface of carbonate minerals and cements were in carbonate-rich alkaline environment, and these portions of U and Th were leached out, resulting in strong loss of U and Th in the Yf (the loss rates are 83% of U and 65% of Th, respectively). From the Yf to the overlying soil layer T1, the carbonate components were completely dissolved, and the U and Th released from the carbonate lattice showed different behaviors, where U was completely leached and Th tended to stay in the weathered residue. Thus, in the soil layer T1 formed by Y or Yf , the residual U was the inheritance of the U in the acid insoluble phase of Y; For Th, it not only inherited the Th of acid insoluble phase of Y, but also superimposed the Th from carbonate lattice in Y. On the other hand, during the evolution process from Y to Yf and to soil layer T1, with the dissolution of carbonate, the acid insoluble phase also showed a significant tendency of chemical weathering. However, the U and Th in the Y acid insoluble phase were not leached with the decomposition of the acid insoluble phase but were redistributed among the residual phases. For the geochemical behaviors of U and Th in the evolution of soil profile (T1~T12), they were subjected to the occurrence speciation of U and Th in T1 and the change of U and Th occurrence speciation with the upward direction of soil profile. The U and Th released from the carrier minerals were mainly redistributed among the residual solid phases, which weakened the intensity of their further loss. This study deepens the understanding of the geochemical behavior of radionuclides in karst environment and provides reference for the treatment of radioactive pollution in karst areas.

Anaerobic purinolytic enzymes enable dietary purine clearance by engineered gut bacteria.

Uric acid, the end product of purine degradation, causes hyperuricemia and gout, afflicting hundreds of millions of people. The debilitating effects of gout are exacerbated by dietary purine intake, and thus a potential therapeutic strategy is to enhance purine degradation in the gut microbiome. Aerobic purine degradation involves oxidative dearomatization of uric acid catalyzed by the O2-dependent uricase. The enzymes involved in purine degradation in strictly anaerobic bacteria remain unknown. Here we report the identification and characterization of these enzymes, which include four hydrolases belonging to different enzyme families, and a prenyl-flavin mononucleotide-dependent decarboxylase. Introduction of the first two hydrolases to Escherichia coli Nissle 1917 enabled its anaerobic growth on xanthine as the sole nitrogen source. Oral supplementation of these engineered probiotics ameliorated hyperuricemia in a Drosophila melanogaster model, including the formation of renal uric acid stones and a shortened lifespan, providing a route toward the development of purinolytic probiotics.

Highly pathogenic porcine reproductive and respiratory syndrome virus-induced inflammatory response in porcine pulmonary microvascular endothelial cells and effects of herbal ingredients on main inflammatory molecules.

The role of microvascular endothelial cells (MVECs) in viral infection has received increasing attention. Our previous study demonstrated the susceptibility of porcine pulmonary MVECs to highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV), while their responses to the viral infection remain unclear. This study aimed to understand effects of the HP-PRRSV infection on functions of porcine pulmonary MVECs and the intervention effects of Chinese herbal ingredients on them. Highly purified porcine pulmonary MVECs were separated using CD31-immunomagnetic beads and infected with HP-PRRSV JXA1 and HN strain. The virus particles in cells and the ultrastructural pathological changes of cells were revealed by transmission electron microscopy. High-throughput transcriptome sequencing indicated that 104 and 228 genes were differentially expressed at 36 h post-infection, respectively, including many inflammatory molecules such as interleukins, chemokines, and adhesion molecules. The expression kinetics of HP-PRRSV-induced IL-1α, IL-6, IL-8, and VCAM-1 were characterized at the mRNA and protein levels. Luteolin significantly down-regulated HP-PRRSV-induced increase of the four molecules at both levels, and glycyrrhetinic acid and baicalin reduced that of IL-6 and VCAM-1. Our results suggest that porcine pulmonary MVECs play important roles in the inflammatory lung injury caused by HP-PRRSV infection and that herbal ingredients have potential regulatory effects on the HP-PRRSV-induced dysfunction of MVECs.

308-nm excimer lamp with 0.03% tacrolimus ointment is safe and effective to treat children with non-segmental vitiligo.

Introduction: A 308-nm excimer lamp combined with topical medicines has been used to treat vitiligo. However, few studies have evaluated its efficacy and influencing factors in children. Aim: We investigated the clinical effects and factors influencing the effectiveness of a 308-nm excimer lamp combined with 0.03% tacrolimus ointment in treating children with non-segmental vitiligo. Material and methods: A retrospective interventional case-series study was performed on 73 patients with non-segmental vitiligo treated with combination therapy. The duration of treatment ranged from 1 to 24 months, and the total number of treatments ranged from 4 to 78 sessions. We evaluated different treatment factors, including the number of treatments with a 308-nm excimer lamp, location, dose, disease course, and adverse reactions. Results: Overall, 105 leukodermas were treated: 36.2% had disappeared completely. The efficiency rate was 81.9% after a median treatment duration of 10.5 months. The treatment was most effective for the face and neck. Patients with a short disease duration showed a better response (disease duration shorter than 12 months). Reported adverse reactions were mild. Conclusions: Treatment using a 308-nm excimer lamp and 0.03% tacrolimus ointment is a safe and valuable treatment for children with non-segmental vitiligo.

Rod-shape MSN@MoS2 Nanoplatform for FL/MSOT/CT Imaging-Guided Photothermal and Photodynamic Therapy.

Rod-shape nanoplatform have received tremendous attention owing to their enhanced ability for cell internalization and high capacity for drug loading. MoS2, widely used in electronic devices, electrocatalysis, sensor and energy-storage, has been studied as photothermal agents over the years. However, the efficacy of rod-shape MoS2 based photothermal agents for photothermal therapy has not been studied before. Here, a near-infrared (NIR) light-absorbing MoS2 nanosheets coated mesoporous silica nanorods with human serum albumin (HSA) modifying and Ce6 loading (MSNR@MoS2-HSA/Ce6) were constructed for combined photothermal and photodynamic therapy. Methods: The near-infrared (NIR) light was used to trigger the synergistic anti-tumor therapy. In addition, breast cancer cell line was applied to evaluate the in vitro anti-tumor activity. The multi-modal imaging capacity and tumor-killing efficiency of the designed nanocomposites in vivo was also demonstrated with the 4T1 tumor-bearing mouse model. Results: These nanocomposites could not only perform NIR light triggered photodynamic therapy (PDT) and photothermal therapy (PTT), but also achieve in vivo fluorescence (FL) /multispectral optical tomography (MSOT)/X-ray computed tomography (CT) triple-model bioimaging. What's more, the rod-shape nanoplatform could be endowed with better anti-tumor ability based on the EPR effect and HSA-mediated active tumor targeting. At the same time, the hyperthermia generated by MoS2 could synergistically improve the PDT effect with the acceleration of the blood flow, leading to the increase of the oxygen level in tumor tissue. Conclusion: MSNR@MoS2-HSA/Ce6 proves to be a promising multi-functional nanoplatform for effective treatment of tumor.

MSOT/CT/MR imaging-guided and hypoxia-maneuvered oxygen self-supply radiotherapy based on one-pot MnO2-mSiO2@Au nanoparticles.

Radiotherapy (RT) is one of the most widely applied treatments for cancer therapy in clinics. Herein, we constructed innovative multifunctional nanotheranostic MnO2-mSiO2@Au-HA nanoparticles (MAHNPs) based on one-pot MnO2-mSiO2 nanohybrids (MNHs) and gold nanoparticles (AuNPs) for multispectral optoacoustic tomography (MSOT)/computed tomography (CT) and magnetic resonance (MR) imaging-guided hypoxia-maneuvered radiotherapy. The MNHs were prepared via a facile one-pot approach, which avoided the leakage of MnO2 nanoparticles and increased the synthetic efficiency. The Mn2+ ions triggered the breakdown of endogenous H2O2 to generate O2 to convert the hypoxic tumor micro-environment (TME), thus enhancing radiotherapy by self-supply oxygen. In addition, hyaluronic acid (HA) was employed to modify the surface of the MnO2-mSiO2@Au nanoparticles to improve their biocompatibility and cellular uptake. The well-designed nanoparticles could perform remarkable photothermal therapy (PTT) and hypoxia-maneuvered radiotherapy (RT) simultaneously and MSOT/CT/MR imaging. The in vivo studies showed that the MAHNPs achieved almost total suppression of tumor growth without observable recurrence, which raises new possibilities for clinical nanotheranostics with multimodal diagnostic and therapeutic coalescent design.

Rodlike MSN@Au Nanohybrid-Modified Supermolecular Photosensitizer for NIRF/MSOT/CT/MR Quadmodal Imaging-Guided Photothermal/Photodynamic Cancer Therapy.

Recently, rodlike nanomaterials with specific aspect ratio for efficient cellular uptake have received enormous attention. For functional nanomaterials, such as photothermal agents, large surface areas for their rod-shaped exterior that increase the amount of light absorbed would lead to a higher absorption coefficient as well as drug-loading property. In this project, we coated rodlike mesoporous silica with gold nanoshells (MSNR@Au hybrid), modifying them with ultrasmall gadolinium (Gd)-chelated supramolecular photosensitizers, TPPS4 (MSNR@Au-TPPS4(Gd)), which could be applied to near-infrared fluorescence/multispectral optoacoustic tomography/computed tomography/magnetic resonance imaging and imaging-guided remotely controlled photothermal (PTT)/photodynamic (PDT) combined antitumor therapy. Gold nanoshells, as a perfect PTT agent, were used to assemble the rodlike mesoporous silica nanoparticles with larger superficial area and higher drug loading, thus obtaining the MSNR@Au hybrid. HS-ß-CD, which was used as the host, was adsorbed on the gold nanoshell (MSNR@Au-ß-CD) to link TPPS4(Gd) through the host-guest reaction, thus forming CD-TPPS4 supramolecular photosensitizers (supraPSs). Compared with conventional PSs, supraPSs have host screens, which could reduce the self-aggregation of TPPS4, and consequently generate 1O2 with high efficiency. The in vivo quadmodal imaging of MSNR@Au-TPPS4(Gd) nanoparticles revealed an intensive tumor uptake effect after injection. The in vivo antitumor efficacy further testified that the synergistic therapy, which was more efficient than any other monotherapy, exhibited an excellent tumor inhibition therapeutic effect. As a result, this encourages to further explore multifunctional theranostic nanoparticles based on gold shells for combined cancer therapy.

Ultrasmall MoS2 Nanodots-Doped Biodegradable SiO2 Nanoparticles for Clearable FL/CT/MSOT Imaging-Guided PTT/PDT Combination Tumor Therapy.

Recently, we developed ultrasmall molybdenum disulfide (MoS2) quantum dots for computed tomography (CT) and multispectral optoacoustic tomography (MSOT) imaging-guided photothermal therapy (PTT). But, due to rapid body elimination and limited blood circulation time, the tumor uptake of the dots is low. In our study, this problem was solved via designing an amino-modified biodegradable nanomaterial based on MoS2 quantum-dots-doped disulfide-based SiO2 nanoparticles (denoted MoS2@ss-SiO2) for multimodal application. By integrating the MoS2 quantum dots into clearable SiO2 nanoparticles, this nanoplatform with an appropriate particle size can not only degrade and excrete in a reasonable period induced by redox responsiveness of glutathione but also exhibit a high tumor uptake due to the longer blood circulation time. Moreover, hyaluronic acid and chlorin e6 (Ce6) were adsorbed on the outer shell for tumor-targeting effect and photodynamic therapy, respectively. So, this biodegradable and clearable theranostic nanocomposite, which is applicable in integrated fluorescence/CT/MSOT imaging-guided combined photothermal therapy (PTT) and photodynamic therapy, is very promising in biomedical applications in the future.

Photothermally activatable PDA immune nanomedicine combined with PD-L1 checkpoint blockade for antimetastatic cancer photoimmunotherapy.

Photothermal therapy (PTT) has shown promising potential and bright prospects in damaging primary tumors; however, it is limited to metastatic and recrudescent tumors as PTT requires straightforward light irradiation. Moreover, metastatic and recrudescent tumor immunosuppression due to host T-cell antitumor activity is dramatically impeded because of programmed cell death 1 ligand (PD-L1) and programmed cell death receptor 1 (PD-1) pathways and immune checkpoint blockade (ICB) therapy. In this work, we demonstrate that PTT combined with ICB could not only eliminate primary tumors, but also prevent tumor metastasis to the lungs/liver. In particular, we have designed immunoadjuvant nanomedicine carriers on the basis of polydopamine (PDA) simultaneously loaded with resiquimod (R848)-a kind of toll-like receptor 7 (TLR7) agonist-and carbon dots (CDs)-a fluorescent agent. This nanomedicine is defined as PDA-PEG-R848-CD nanoparticle (NP). The multitasking PDA-PEG-R848-CD NPs can destroy 4T1 breast tumors by PTT under near-infrared laser irradiation in addition to generating tumor-associated antigens. Moreover, the PTT effect triggered the release of R848, thereby inducing a strong antitumor immune response. Meanwhile, this synergistic therapy also shows the abscopal effects by completely inhibiting the growth of untreated distant tumors by effectively triggering the tumors infiltrated by CD3/CD8. Such findings suggest that PDA-PEG-R848-CD NPs could significantly potentiate the systemic therapeutic efficiency of PD-L1 checkpoint blockade therapy by activating both innate and adaptive immune systems in the body.