GSH/pH dual response drug delivery system for photothermal enhanced gene-immunotherapy.

Breast cancer has emerged as a leading cause of mortality among women. Photothermal therapy represents a recent therapeutic modality for eradicating localized tumors, albeit hindered by its limited penetration into tumor tissues. Recognizing the potential of photothermal therapy to induce immunogenic cell death in tumor cells, we explored a gene delivery approach utilizing small interfering RNA targeting programmed death ligand 1 (PD-L1), abbreviated as siPD-L1, to bolster the anti-tumor immune response elicited by this therapy. Nonetheless, the suboptimal release efficiency and inherent instability of RNA molecules have posed challenges to their therapeutic efficacy. In this study, we designed a glutathione (GSH)/pH-responsive micelle system, employing biocompatible and low-toxicity polyethyleneimine in conjunction with structurally robust pluronic P123, to encapsulate both indocyanine green (ICG) and siPD-L1 for precise targeting in breast cancer treatment. The resulting PSP/ICG/siPD-L1 nanocarrier demonstrated admirable biocompatibility and stability. Upon internalization into tumor cells, this nanocarrier exhibited rapid release of both ICG and siPD-L1, responding to the acidic tumor microenvironment and GSH conditions. The inclusion of siPD-L1 effectively downregulated the expression of PD-L1 on the tumor cell surface, thereby impeding tumor growth. Additionally, ICG demonstrated a photothermal effect when exposed to near-infrared light. Both in vitro and in vivo investigations substantiated the nanocarrier's efficacy against tumor cells, culminating in the complete ablation of 4T1 tumors in situ. Consequently, PSP/ICG/siPD-L1 emerges as a promising nanocarrier candidate for augmenting anti-tumor immunity through the synergistic combination of photothermal therapy and gene-based intervention.

Effects of acupuncture synchronized rehabilitation therapy on upper limb motor and sensory function after stroke: a study protocol for a single-center, 2 × 2 factorial design, randomized controlled trial.

Background: Upper limb function reconstruction has been an important issue in the field of stroke rehabilitation. Due to the complexity of upper extremity dysfunction in stroke patients, the clinical efficacy produced by central or peripheral stimulation alone is limited. For this reason, our group has proposed acupuncture synchronized rehabilitation therapy (ASRT), i.e., simultaneous scalp acupuncture and intradermal acupuncture during rehabilitation. Pre-experiments results showed that this therapy can effectively improve the motor and sensory functions of upper limbs in post-stroke patients, but the clinical efficacy and safety of ASRT need to be further verified, and whether there is a synergistic effect between scalp acupuncture and intradermal acupuncture also needs to be studied in depth. Therefore, we designed a randomized controlled trial to compare the efficacy and safety of different therapies to explore a more scientific "synchronous treatment model." Methods: This is a single-center, randomized controlled trial using a 2 × 2 factorial design. We will recruit 136 stroke survivors with upper extremity dysfunction and randomize them into four groups (n = 34). All subjects will undergo routine treatment, based on which the Experimental Group 1: rehabilitation training synchronized with intradermal acupuncture treatment of the affected upper limb; Experimental Group 2: rehabilitation training of the affected upper limb synchronized with focal-side scalp acupuncture treatment, and Experimental Group 3: rehabilitation training synchronized with intradermal acupuncture treatment of the affected upper limb synchronized with focal-side scalp acupuncture treatment; Control Group: rehabilitation training of the affected upper limb only. The intervention will last for 4 weeks, 5 times a week. Both acupuncture treatments will be performed according to the Revised Standards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA). The primary outcome indicators for this trial are Fugl-Meyer Assessment-Upper Extremity and Somatosensory Evoked Potential. Secondary outcome indicators include Wolf Motor Function Test, Upper Extremity Function Test, revised Nottingham Sensory Assessment Scale, Diffusion Tensor Imaging, and Modified Barthel Index. The incidence of adverse events will be used as the indicator of safety. Discussion: The study will provide high-quality clinical evidence on whether ASRT improves upper limb motor and sensory function and activities of daily living (ADL) in stroke patients, and determine whether scalp acupuncture and intradermal acupuncture have synergistic effects. Clinical trial registration: https://www.chictr.org.cn/, Chinese Clinical Trial Registry [ChiCTR2200066646].

Dietary fatty acids intake and all-cause and cardiovascular mortality in patients on peritoneal dialysis.

BACKGROUND & AIMS: The relationship between dietary fatty acids (FA) and clinical outcomes are relatively lacking in non-dialyzed and dialyzed chronic kidney disease (CKD) population, resulting in insufficient guide about the dietary FA intake in this population. In this study, we aimed to observe the association between the intake of total or different types of FA and all-cause and cardiovascular (CV) mortality in patients undergoing peritoneal dialysis (PD). METHODS: This is a prospective cohort study with data retrospectively analyzed in 881 patients undergoing PD. Dietary FA intake measured by 3-day dietary records. The outcomes were defined as all-cause and CV death. Baseline FA intake and time-averaged FA intake were categorized by tertiles based on the distribution among the study population. We used univariate and multivariate Cox proportional regression models to determine the association between amounts and types of FA and all-cause and CV mortality. RESULTS: During a median follow up of 45 months, 93 patients were still being maintained on PD, 467 had died, including 189 (40.5%) attributable to CV death. Compared to patients in the low tertile of total FA (TFA) intake at baseline group, the middle or/and high tertile groups were more likely to be male, younger, well-educated and better nutritional status (P < 0.05). At the baseline, no association was found between all-cause and CV death in either total or different types of FA after adjusting for nutritional variables. As for time-averaged analyses, the associations of TFA, saturated FA (SFA), monounsaturated FA (MUFA), ω-3 and ω-6 polyunsaturated FA (PUFA) and all-cause mortality were weakened after adjustment for laboratory and nutrients variables. However, PUFA independently reduced 5% of mortality even after adjustment for laboratory and nutrients variables [HR 0.95 (0.91, 0.99), P = 0.023], and the ratio of MUFA/PUFA was positively associated with the risk for all-cause mortality [HR 1.05 (1.01, 1.09), P = 0.008]. Furthermore, each 10% increase of the ratio of ω-6/ω-3 was only weakly associated with the risk for all-cause mortality [HR 1.02 (1.00, 1.04), P = 0.034]. As for CVD mortality, the impacts of total and each type of FA disappeared after adjustment for laboratory or nutrients variables. CONCLUSIONS: Time-averaged PUFA intake was independently associated with a lower risk for all-cause mortality in our PD cohort, while the higher ratio of MUFA/PUFA and ω-6/ω-3 increased all-cause mortality. More observational and interventional researches are needed to determine these associations.

[Mechanism of acupuncture and moxibustion in ameliorating liver injury induced by DDP by regulating apoptosis factors Caspase-3, Caspase-8 and Caspase-9].

OBJECTIVE: To investigate the mechanism of the effect of acupuncture and moxibustion on improving liver injury by observing the changes of cysteine protease (Caspase) associated with hepatocyte apoptosis based on cisplatin (DDP) induced liver injury model mice. METHODS: Forty KM mice were randomly divided into control group, model group, acupuncture group and moxibustion group, with 10 mice in each group. The liver injury model was replicated by intraperitoneal injection of DDP. In the acupuncture group and the moxibustion group, acupuncture and moxibustion were performed at"Dazhui"(GV14), and bilateral "Ganshu"(BL18), "Shenshu"(BL23), and "Zusanli"(ST36), respectively, once per day for 5 d. General condition of mice in each group were observed;The activities of AST, ALT and GLDH in mice serum were detected by biochemical method. ELISA and Western blot assay were used to detect Caspase-3, Caspase-8 and Caspase-9 contents and protein expression in the liver tissues of each group of mice, respectively. RESULTS: Compared with the control group, the general condition of the mice in the model group was poorer, and the Caspase-3, Caspase-8 and Caspase-9 contents and protein expressions in liver tissues and the activities of AST, ALT and GLDH in serum were increased (P<0.05). Compared with the model group, the general condition of the mice in the acupuncture and moxibustion groups improved, and the Caspase-3, Caspase-8 and Caspase-9 contents and protein expressions in liver tissues and activities of AST, ALT and GLDH in serum were decreased (P<0.05). CONCLUSION: Acupuncture and moxibustion can reduce liver injury due to DDP chemotherapy by modulating the expression of apoptotic factors Caspase-3, Caspase-8 and Caspase-9 in liver tissues of DDP model mice and improving liver function, which may be one of the mechanisms of the effect of acupuncture and moxibustion to ameliorates liver injury after DDP chemotherapy.

Distribution and speciation of arsenic in seasonally stratified reservoirs: Implications for biotransformation mechanisms governing interannual variability.

HPLC-ICPMS was used to analyze the spatiotemporal variation of As species in different sections and tributaries of the Aha Reservoir over four seasons, and the migration and transformation mechanisms were clarified by combined analysis of hydrochemical parameters and microbial composition. The results showed that the internal release of As from the reservoir sediments is mainly due to the reduction of iron oxide and the release of adsorbed As(V). The average proportion of As(III) increased from 27.2% in autumn to 46.5% in summer, 68.9% in winter, and up to 70.8% in spring. In spring and summer, the high concentration of As(III) and organic arsenic in the epilimnion under phosphorus restriction was caused by the reductive metabolism of phytoplankton after intake of As(V). The arsenic species in the metalimnion were mainly affected by the oxidation-reduction potential (ORP). In summer and autumn, As-oxidizing bacteria used As(III) as an electron donor, and nitrate played an important role as an electron acceptor, maintaining the dominance of As(V) in the hypolimnion. However, in winter and spring, temperature-controlled ORP was the main process, which was dominated by As(III). In conclusion, As species show annual cycles in different layers of seasonally thermal stratified reservoirs. It provides a systematic mechanism of As species transformation in reservoirs, especially the effect of biological transformation mechanism.

Phosphorus excess changes rock phosphate solubilization level and bacterial community mediating phosphorus fractions mobilization during composting.

This study investigated the changes of phosphorus (P) fractions, bacterial community and their response to available P or carbon (C):P during composting with different rock phosphate (RP) addition levels. Results showed that adding RP at 10% or 15% promoted the rise of temperature, maturity and Olsen P accumulation in composting, which had a higher amount of RP solubilization than other groups. Available P changed bacterial composition and decreased diversity in composts. RP solubilization efficiency was negatively correlated to C:P ratio and the highest (22.7%) when 10% RP was added, in which bacterial community changed from "function redundancy" to "intensive P-solubilization". Low C:P ratio (〈300) increased the RP solubilization ratio especially within 135-160. Therefore, this study proposed that adding P-rich substrates to decrease C:P ratio could regulate P-solubilizers' activity for increasing RP solubilization efficiency during composting.

The composites based on plasticized starch and graphene oxide/reduced graphene oxide.

The graphite was oxidized to prepare graphene oxide (GO), and GO was reduced by glucose to obtain reduced graphene oxide (RGO) sheet. There were abundant and residual oxygen-containing groups on GO and RGO, respectively. Compared to graphite, the GO and RGO sheets appeared flat and transparent, and the aqueous suspensions followed the Lambert-Beer's law well. The composites were also fabricated by using GO and RGO as the filler in plasticized-starch (PS) matrix. Because of more oxygen-containing groups, GO could form the stronger interaction with PS matrix than RGO. And GO/PS composites exhibited better tensile strength, elongation at break and moisture barrier than RGO/PS composites, but lower thermal stability. GO/PS composites could protect against UV light, while the conductivities of RGO/PS composites could reach 1.07×10(-4), 6.92×10(-4) and 0.01 S/cm, respectively stored at RH50, 75 and 100%.

[Study on solid dispersion of binary vector of tanshinone II A].

OBJECTIVE: To prepare the solid dispersion of tanshinone II A (TS II A) by the combined application of nano-silica and poloxamer 188 (F68), in order to observe its dissolution and stability. METHOD: Tanshinone II A solid dispersion was prepared by the solvent method with nano-silica and poloxamer 188 as binary vectors. Its physical characteristics, in vitro dissolution and stability were further assessed. RESULT: The tanshinone II solid dispersion was prepared with the weight ratio of nano-silica and poloxamer 188 of 1: 3. The differential scanning calorimetry (DSC) demonstrated that Tanshinone II A existed in vectors as amorphous state. The in vitro dissolution of tanshinone II A solid dispersion is up to 90% at 60 min. Accelerating experiment showed that content and in vitro dissolution of tanshinone II A solid dispersion did not change after storage over 3 months. CONCLUSION: Solid dispersion of binary vector of tanshinone II A can obviously improve the dissolution and stability of tanshinone II in practice.