A multifunctional metal-organic framework nanosystem disrupts redox homeostasis for synergistic therapy.

Synergistic therapies of photodynamic therapy (PDT) and chemodynamic therapy (CDT) via metal-organic frameworks (MOF) for cancer treatment have recently attracted a lot of attentions because of the limitations of insufficient reactive oxygen species (ROS) in single-modality approaches. However, few studies explored on the use of increased ROS synergized with chemotherapy (CT) to address the issue of inadequate anti-tumor efficacy in single-modality regimens. Here, the desired cascade nanoplatforms (noted as MOF(Cu)@Dox-PL NPs) were fabricated by a solvothermal method using tetrakis (4-carboxyphenyl) porphyrin (TCPP) and zirconyl(di)chloride octahydrate (ZrOCl2·8H2O) as raw material, followed by Cu2+ introduced into the porphyrin ring and doxorubicin (DOX) loaded into the nanoframework. In addition, the nanoparticles (NPs) were electrostatically and hydrophobically coated with phospholipid (PL) to improve the biocompatibility of the nanosystems. Singlet oxygen (1O2) was created by the MOF(Cu)@Dox-PL NPs to disturb intracellular redox equilibrium. The acidic microenvironment in cancer cells may cause the prior release of DOX, which encourages the production of hydrogen peroxide (H2O2). And the doped Cu2+ could deplete overexpressed reduced glutathione (GSH) to produce hydroxyl radicals (·OH) by catalyzing H2O2, further causing redox dyshomeostasis. In vivo experiments revealed that MOF(Cu)@Dox-PL nanosystem possessed good biosafety and a compelling therapeutic effect in 4T1 tumor-bearing mice. As a novel nanosystem, MOF(Cu)@Dox-PL NPs showed great potential in synergistic therapy based on redox dyshomeostasis for improving anti-tumor efficacy with high specificity.

Traceless encryption approach for physical layer security in coherent optical communications system.

We proposed and numerically studied a traceless encryption approach for physical layer security in coherent optical communications system, the most attractive advantage of which is that it is hard for eavesdroppers to be aware that the transmission signal has been encrypted because the modulation formats of encrypted signal are still the regular ones, i.e. traceless encryption. In the proposed approach, the phase only or the combination of phase and amplitude dimensions can be used for encryption and decryption. Three simple encryption rules are designed and used to investigate the encryption security performance of the scheme, in which the QPSK signal can be encrypted to be as 8PSK, QPSK and 8QAM. The results show that three simple encryption rules can cause 37.5%, 25%, 62.5% of user signal binary codes to be misinterpreted by the eavesdroppers, respectively. When the modulation formats of encrypted signal and user signal are identical, the scheme can not only cover up the real information, but also have a potential application at misleading eavesdroppers. The impacts of the control light peak power at the receiver on the decryption performance are also analysed, the results indicate that the decryption performance of the scheme has a good tolerance to the peak power fluctuation of control light at the receiver.

Evaluation of the Association between Low-Density Lipoprotein (LDL) and All-Cause Mortality in Geriatric Patients with Hip Fractures: A Prospective Cohort Study of 339 Patients.

BACKGROUND: Many factors affect the prognosis of hip fractures in the elderly. Some studies have suggested a direct or indirect association among serum lipid levels, osteoporosis, and hip fracture risk. LDL levels were found to have a statistically significant nonlinear U-shaped relationship with hip fracture risk. However, the relationship between serum LDL levels and the prognosis of patients with hip fractures remains unclear. Therefore, in this study, we assessed the influence of serum LDL levels on patient mortality over a long-term follow-up period. METHODS: Elderly patients with hip fractures were screened between January 2015 and September 2019, and their demographic and clinical characteristics were collected. Linear and nonlinear multivariate Cox regression models were used to identify the association between LDL levels and mortality. Analyses were performed using Empower Stats and R software. RESULTS: Overall, 339 patients with a mean follow-up period of 34.17 months were included in this study. Ninety-nine patients (29.20%) died due to all-cause mortality. Linear multivariate Cox regression models showed that LDL levels were associated with mortality (HR = 0.69, 95%CI: 0.53, 0.91, p = 0.0085) after adjusting for confounding factors. However, the linear association was unstable, and nonlinearity was identified. An LDL concentration of 2.31 mmol/L was defined as the inflection point for prediction. A LDL level < 2.31 mmol/L was associated with mortality (HR = 0.42, 95%CI: 0.25, 0.69, p = 0.0006), whereas LDL > 2.31 mmol/L was not a risk factor for mortality (HR = 1.06, 95%CI: 0.70, 1.63, p = 0.7722). CONCLUSIONS: The preoperative LDL level was nonlinearly associated with mortality in elderly patients with hip fractures, and the LDL level was a risk indicator of mortality. Furthermore, 2.31 mmol/L could be considered a predictor cut-off for risk.

[Treatment of aseptic ulnar diaphyseal nonunion with locking compression plate and autogenous iliac bone graft].

OBJECTIVE: To investigate the clinical results of locking compression plate combined with autologous iliac bone graft in the treatment of aseptic ulnar nonunion. METHODS: From March 2009 to July 2017, 22 patients with aseptic ulnar diaphyseal nonunion with complete follow-up data were treated with surgery, including 12 males and 10 females, aged from 16 to 58 (39.7±9.9) years old and ranging in course of disease from 10 to 192 (39.4±55.7) months. There were 15 atrophic nonunions, 5 hypertrophic nonunions and 2 synovial pseudo-articular nonunions. After debridement of the nonunion, locking compression plate was used to fix the nonunion and autogenous iliac bone graft was given. Bone healing rate, surgical complications and clinical results were evaluated. RESULTS: All the patients were followed up, and the duration ranged from 13 to 42 months, with a mean of (22.5±8.2) months, and 1 patient did not heal. Visual analogue pain scores ranged from 0 to 3 (0.9±0.9). Pronation of forearm was 47 to 86 (69.0±14.7) degrees, supination was 35 to 85 (63.0±9.4) degrees, wrist flexion was 20 to 80 (51.0±10.2) degrees, wrist flexion was 32 to 88 (71.0±11.7) degrees, elbow flexion contracture was 0 to 25 (9.0±5.6) degrees, further flexion was 105 to 150 (134.0±13.9) degrees, and grip strength was 87% on the opposite side. According to the Anderson scoring system, 8 cases were excellent, 11 were satisfied, 2 were not satisfied, and 1 was failed. CONCLUSIONS: LCP combined with autologous iliac bone graft can effectively treat aseptic ulna diaphyseal nonunion.

Knockdown of PRMT1 suppresses IL-1ß-induced cartilage degradation and inflammatory responses in human chondrocytes through Gli1-mediated Hedgehog signaling pathway.

Osteoarthritis (OA) is characterized by articular cartilage degradation and joint inflammation. The purpose of the present study is to elucidate the role of the specific function of PRMT1 in chondrocytes and its association with the pathophysiology of OA. We observed that the expression of PRMT1 was apparently upregulated in OA cartilage, as well as in chondrocytes stimulated with IL-1ß. Additionally, knockdown of PRMT1 suppressed interleukin 1 beta (IL-1ß)-induced extracellular matrix (ECM) metabolic imbalance by regulating the expression of MMP-13, ADAMTS-5, COL2A1, and ACAN. Furthermore, silencing of PRMT1 dramatically declined the production of prostaglandin E2 (PGE2) and nitric oxide as well as the level of pro-inflammatory cytokine IL-6 and TNF-α. Mechanistic analyses further revealed that IL-1ß-induced activation of the Hedgehog/Gli-1 signaling is suppressed upon PRMT1 knockdown. However, the effects of inhibition of PRMT1-mediated IL-1ß-induced cartilage matrix degradation and inflammatory response in OA chondrocytes were obviously abolished by Hedgehog agonist Purmorphamine (Pur). Our data collectively suggest that silencing of PRMT1 exerts anti-catabolic and anti-inflammatory effects on IL-1ß-induced chondrocytes via suppressing the Gli-1 mediated Hedgehog signaling pathway, indicating that PRMT1 plays a critical role in OA development and serves as a promising therapeutic target for OA.

[The protective effect of chlorophyllin against oxidative damage and its mechanism].

OBJECTIVE: To investigate whether chlorophyllin could protect human umbilical vein endothelial cell (HUVEC) against oxidative damage by inducing the expression of heme oxygenase-1 (HO-1) and to explore the underlying mechanism. METHODS: The cellular protection of chlorophyllin against oxidative damage was detected by cell-survival assay with flow cytometry. The level of free radicals was detected directly by electron spin resonance spectra. The induced expression of HO-1 was shown by RT-PCR, Western blot, immunofluorescence confocal laser microscopy and enzymatic activity test. Whether the activation of PI3K/Akt pathway was involved was detected by Western blot. RESULTS: Chlorophyllin could protect HUVEC against oxidative damage caused by H2O2 via scavenging the excessive free radicals. Chlorophyllin treatment could induce expression of HO-1 in a dose- and time-dependent manner. The activation of PI3K/Akt pathway was required in the induction of HO-1. LY294002, the specific inhibitor of PI3K, could suppress the activation of PI3K/Akt and the induced expression of HO-1 in a dose-dependent manner. CONCLUSIONS: Chlorophyllin shows cellular protection against oxidative damage by counteracting the excessive free radicals. Up-regulation of HO-1 expression plays a pivotal role in the protection of chlorophyllin, while the activation of PI3K/Akt signaling pathway is required in the induction of HO-1.

Layer-by-layer assembly of two temperature-responsive homopolymers at neutral pH and the temperature-dependent solubility of the multilayer film.

We fabricated a layer-by-layer (LbL) film of temperature-responsive homopolymers at neutral pH and studied its temperature-dependent solubility. We first measured the cloud point of mixed solutions of temperature-responsive polymers. The significant decrease of cloud point suggested that the intermolecular interaction between two polymer chains of different kinds was stronger than that between two polymer chains of the same kind. Strong intermolecular interaction between two polymer chains of different kinds is a prerequisite for LbL assembly. On the basis of the decrease of cloud point of mixed solutions of temperature-responsive homopolymers, we selected poly(N-vinylcaprolactam) (PVCL) and poly(2-hydroxypropyl acrylate) (PHPA) for LbL assembly. LbL films of the two polymers were fabricated at neutral pH at a constant temperature. When the film was immersed in purified water at a temperature lower than the assembly temperature, it can be partially dissolved with a diffusion-limited dissolution process. The temperature-responsive solubility of the LbL film is closely connected to the phase behavior of mixed solutions of the two polymers. Additionally, as compared to multilayer films of neutral polymers and poly(carboxylic acid)s, the PVCL/PHPA multilayer film is relatively stable when it was immersed in buffer solutions near physiological pH at the assembly temperature. Such LbL films with temperature-responsive solubility might be used as a dissolvable film or a smart capsule.

[Analysis of developing feature of pneumoconiosis].

OBJECTIVE: To get the message about the developing feature of pneumoconiosis by analyzing the data from 353 cases of pneumoconiosis diagnosed in our hospital recent 6 years. METHODS: To analyze the onset age, onset service years and incubation period of 353 cases of pneumoconiosis, especially in silicosis, coal worker's pneumoconiosis and potter's pneumoconiosis. RESULTS: 353 patients referred to 10 species of pneumoconiosis, the silicosis, coal worker's pneumoconiosis and potter's pneumoconiosis were accounted for 28.90%, 43.34% and 15.01% of total pneumoconiosis respectively. Diagnosed patients who began to exposed to dust during 1950's to 1980's accounted for 84.99% of all the diagnosed patients. The onset age, onset service years and incubation period of silicosis, coal worker's pneumoconiosis and potters pneumoconiosis all showed a shorten trend compared each other every decade, especially after 1980's, but excluded potter's pneumoconiosis because of that the ceramics industry switched to other products in Beijing. There was a positive correlation relationship between average onset age and incubation period in three main species of pneumoconiosis mentioned above, but no significant difference could be seen in average promotion years. Additionally, comparing with other type of work, jade machining workers showed such a characteristic as younger onset and short incubation period. CONCLUSION: The development situation of silicosis, coal worker's pneumoconiosis is still no so optimistic, and the strict surveillance and administration especially to the township enterprises with poor production conditions should get further strengthen.

[Effects of baicalin on pulmonary functions of acute respiratory distress syndrome induced by oleic acid in rats].

OBJECTIVE: To investigate the effect of baicalin on pulmonary functions and its mechanism during the development of acute respiratory distress syndrome (ARDS) induced by oleic acid (OA) in rats. METHODS: Rats were randomized into 5 groups: control, ARDS (OA induction, 0.12 mg/kg), baicalin-treated group (150 mg/kg), baicalin-treated group (300 mg/kg) and baicalin-treated group (450 mg/kg). The blood samples and lung tissue were collected at 10 min, 1, 2 and 6 h after OA injection. The lung concentration of myeloperoxidase (MPO) was detected by an ELISA (enzyme-linked immunosorbent assay) kit. Meanwhile, blood gas analysis and pulmonary pathological examination were also performed. RESULTS: The level of arterial oxygen partial pressure and oxygenation index decreased (P < 0.01 vs. control) and oxygenation index (190 mm Hg, 1 mm Hg = 0.133 kPa) reached the diagnostic standard of ARDS at 2 h in ARDS group. In baicalin-treated group (150 mg/kg and 300 mg/kg), the level of arterial oxygen partial pressure and oxygenation index increased versus the ARDS group. In baicalin-treated group (450 mg/kg), the level of arterial oxygen partial pressure was undifferentiated at 1, 2 and 6 h (P > 0.05) and decreased at 10 min (46.8 mm Hg, P < 0.05) versus the ARDS group. The level of MPO increased in baicalin-treated (300 mg/kg) and ARDS groups. Compared with the ARDS group, the level of MPO decreased significantly in baicalin-treated group (300 mg/kg) at 10 min, 1 and 2 h. Meanwhile, the pulmonary pathological damage improved in baicalin-treated group (300 mg/kg). CONCLUSION: An appropriate dose of baicalin may improve hypoxemia of ARDS induced by OA in rats. It may be due to the inhibition of MPO activity.