The Effect of Different Factors on Poly(lactic-co-glycolic acid) Nanoparticle Properties and Drug Release Behaviors When Co-Loaded with Hydrophilic and Hydrophobic Drugs.

Poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) are versatile drug nanocarriers with a wide spectrum of applications owing to their extensive advantages, including biodegradability, non-toxic side effects, and low immunogenicity. Among the numerous nanoparticle preparation methods available for PLGA NPs (the hydrophobic polymer), one of the most extensively utilized preparations is the sonicated-emulsified solvent evaporation method, owing to its simplicity, speed, convenience, and cost-effectiveness. Nevertheless, several factors can influence the outcomes, such as the types of concentration of the surfactants and organic solvents, as well as the volume of the aqueous phase. The objective of this article is to explore the influence of these factors on the properties of PLGA NPs and their drug release behavior following encapsulation. Herein, PLGA NPs were fabricated using bovine serum albumin (BSA) as a surfactant to investigate the impact of influencing factors, including different water-soluble organic solvents such as propylene carbonate (PC), ethyl acetate (PA), and dichloromethane (DCM). Notably, the size of PLGA NPs was smaller in the EA group compared to that in the DCM group. Moreover, PLGA NPs showed excellent stability, ascribed to the presence of the BSA surfactant. Furthermore, PLGA NPs were co-loaded with varying concentrations of hydrophilic drugs (doxorubicin hydrochloride) and hydrophobic drugs (celecoxib), and exhibited pH-sensitive drug release behavior in PBS with pH 7.4 and pH 5.5.

Structural Decoration of Porphyrin/Phthalocyanine Photovoltaic Materials.

Porphyrin/phthalocyanine compounds with fascinating molecular structures have attracted widespread attention in the field of solar cells in recent years. In this review, we focus on the pivotal role of porphyrin and phthalocyanine compounds in enhancing the efficiency of solar cells. The review seamlessly integrates the intricate molecular structures of porphyrins and phthalocyanines with their proficiency in absorbing visible light and facilitating electron transfer, key processes in converting sunlight into electricity. By delving into the nuances of intramolecular regulation, aggregated states, and surface/interface structure manipulation, it elucidates how various levels of molecular modifications enhance solar cell efficiency through improved charge transfer, stability, and overall performance. This comprehensive exploration provides a detailed understanding of the complex relationship between molecular design and solar cell performance, discussing current advancements and potential future applications of these molecules in solar energy technology.

Crystallographic and functional studies of a plant temperature-induced lipocalin.

Arabidopsis thaliana temperature-induced lipocalin (AtTIL) is a prototypical member of plant lipocalins and participates in a variety of cellular processes, particularly stress responses. Bioinformatical and physiological studies have proposed its promiscuous ligand-binding ability, but the molecular basis is yet unclear. Here, we report the 1.9-Šcrystal structure of AtTIL in complex with heme. Spectrophotometric absorbance titration with heme yields a dissociation constant of ∼2 micromolar, indicating the relatively weak interaction between AtTIL and heme, which is confirmed by the AtTIL-heme structure. Although binding to retinal or biliverdin is not detected, such possibility can not be precluded as suggested by comparison with other lipocalin structures. These results show that AtTIL is a structural and functional homolog of the bacterial lipocalin Blc.

Pt Nanodot Inlaid Mesoporous NaBiOF Nanoblackberry for Remarkable Signal Amplification Toward Biomarker Detection.

A new ultrasensitive sandwich-type electrochemical immunosensor has been successfully constructed to quantitatively detect carcinoembryonic antigen (CEA) using blackberry-like mesoporous bismuth-based nanospheres NaBiOF (NBOF NSs) inlaid with Pt nanodots (NDs) (BiPt NSs) as the antibody capture and signal-amplifying probe. The growth of Pt NDs inside the holes of NBOF NSs formed the nanozyme inlay outside NBOF NSs, greatly increasing the specific surface area and exposure of the catalytic active sites by minimizing the particle size of the Pt to nanodot scale. Such a blackberry-shaped heterojunction structure of BiPt NSs was well-suited to antibody capture and improved the catalytic performance of BiPt NSs in reducing H2O2, amplifying the signal, and yielding highly sensitive detection of CEA. The use of Au nanoparticle-modified multi-walled carbon nanotubes (Au@MWCNTs) as the electrode substrates significantly enhanced the electron transfer behavior over the electrode surface, further increasing the conductivity and sensitivity of the immunosensor. Remarkably, good compatibility with human body fluid was achieved using the newly developed BiPt-based immunosensor resulting from the favorable biocompatibility and stability of both BiPt NSs and Au@MWCNTs. Benefiting from the double signal amplification strategy and the high biocompatibility, the immunosensor responded linearly to CEA in a wide range from 50 fg/mL to 100 ng/ml with an extremely low detection limit of 3.52 fg/mL (S/N = 3). The excellent detection properties of this new immunosensor were evidenced by the satisfactory selectivity, reproducibility, and stability obtained, as well as the reliable and precise determination  of CEA in actual human blood samples. This work provides a new strategy for the early clinical diagnosis of cancer. Novel blackberry-like mesoporous NaBiOF nanospheres with Pt nanodot inlay were successfully usedto construct a sandwich-type electrochemical immunosensor for the ultra-sensitive detection ofcarcinoembryonic antigen in human blood plasma based on a remarkable signal amplification strategy.

Virtual Screening-Based Study of Novel Anti-Cancer Drugs Targeting G-Quadruplex.

In order to develop new anti-cancer drugs more efficiently and reduce side effects based on active drug targets, the virtual drug screening was carried out through the target of G-quadruplexes and 23 hit compounds were, thus, screened out as potential anticancer drugs. Six classical G-quadruplex complexes were introduced as query molecules, and the three-dimensional similarity of molecules was calculated by shape feature similarity (SHAFTS) method so as to reduce the range of potential compounds. Afterwards, the molecular docking technology was utilized to perform the final screening followed by the exploration of the binding between each compound and four different structures of G-quadruplex. In order to verify the anticancer activity of the selected compounds, compounds 1, 6 and 7 were chosen to treat A549 cells in vitro, the lung cancer epithelial cells, for further exploring their anticancer activity. These three compounds were found to be of good characteristics in the treatment of cancer, which revealed the great application prospect of the virtual screening method in developing new drugs.

Large steering range and low-loss integrated optical phased array with SiN-Si dual-layer non-uniform antenna.

We propose and demonstrate a 64-channel SiN-Si dual-layer optical phased array (OPA). By taking advantages of both SiN and Si materials, high-power handling and efficient modulation could be achieved simultaneously. In addition, steering range and emission loss are improved by introducing the non-uniform dual-layer antenna. Thinned array efficiently utilized in microwave phased array is first introduced to the OPA. Design details and the corresponding simulation results are presented, and the proposed OPA is successfully fabricated and experimentally characterized. 2D scanning with a steering range of 120°×13.9° and with a resolution of 0.052°×2.72° is demonstrated and a total loss of 12.66 dB is also measured, making it promising for high-resolution long-distance light detection and ranging (Lidar) applications.

Crystal phase transition and polyhedron transformation towards the evolution of photoluminescence and the improvement of thermal stability in efficient blue-emitting Ba0.47-xSr0.50+xAl2Si2O8:Eu2.

Investigations into novel single-phase phosphors with outstanding luminescence properties and excellent thermal stability are urgently needed in the lighting field. In this work, a crystal phase transition and polyhedron transformation strategy via cation substitution has been proposed. Via controlling the Sr/Ba ratio, the structural evolution of the phosphor from a monocelsian phase to a hexacelsian or feldspar phase and the variation of the local environments of Eu2+ sites are correspondingly studied in Ba0.47-xSr0.50+xAl2Si2O8:0.03Eu. Consequently, the optimal Ba0.17Sr0.80Al2Si2O8:0.03Eu sample exhibits a higher intensity, up to 15.2-fold that of Ba0.97Al2Si2O8:0.03Eu. A narrower full-width-at-half-maximum of 73 nm, better color purity of 82.96%, and an internal quantum yield of 82.3% can be realized. With an increase in temperature, the emission intensity losses of samples from x = -10.0-47.0% are no more than 10.0% at 473 K. Moreover, a WLED (CCT = 5210 K; CRI = 90.3) fabricated using Ba0.17Sr0.80Al2Si2O8:0.03Eu displays warmer white light than one fabricated using BaMgAl10O17:Eu under the same assembly and test conditions. Analysis shows that the structural evolution with reduced polyhedral symmetry and the condensed crystal structure with fortified rigidity are responsible for the improvement in properties. This discovery demonstrates that the utilization of a crystal phase transition and symmetrical coordination is an efficient way to develop novel efficient phosphors and other related materials.

Crystal structures of cyanobacterial light-dependent protochlorophyllide oxidoreductase.

The reduction of protochlorophyllide (Pchlide) to chlorophyllide (Chlide) is the penultimate step of chlorophyll biosynthesis. In oxygenic photosynthetic bacteria, algae, and plants, this reaction can be catalyzed by the light-dependent Pchlide oxidoreductase (LPOR), a member of the short-chain dehydrogenase superfamily sharing a conserved Rossmann fold for NAD(P)H binding and the catalytic activity. Whereas modeling and simulation approaches have been used to study the catalytic mechanism of this light-driven reaction, key details of the LPOR structure remain unclear. We determined the crystal structures of LPOR from two cyanobacteria, Synechocystis sp. PCC 6803 and Thermosynechococcus elongatus Structural analysis defines the LPOR core fold, outlines the LPOR-NADPH interaction network, identifies the residues forming the substrate cavity and the proton-relay path, and reveals the role of the LPOR-specific loop. These findings provide a basis for understanding the structure-function relationships of the light-driven Pchlide reduction.

Tunable Photoluminescence and Energy Transfer Efficiency in ß-Ca3(PO4)2-Ca9La(PO4)7:Eu2+, Mn2+ Solid Solution Phosphors Introduced by Emptying Site and Structural Confinement Effect for Solid-State Lighting Application.

Full visible emission achieved by a single-phased system is of great interest to researchers for the development of high-quality solid-state lighting devices. Herein, novel Eu2+ and Mn2+ co-doped (1 - x)ß-Ca3(PO4)2-xCa9La(PO4)7 solid solution phosphors are designed to realize single-phased white light emission. The effects of variational x on lattice structure, color-tunable emission, thermal stability, and energy-transfer efficiency from Eu2+ to Mn2+ are systematically investigated. Tunable color emissions are achieved by manipulating the redistributions of Eu2+ ions among the different cationic sites under the influence of generated empty site in the M(4) site. Meanwhile, the changes of critical distances among the Eu2+ and Mn2+ caused by the variational x results in the changes of energy-transfer efficiency from different Eu2+ luminescent centers to Mn2+ due to the existence of structural confinement effect. The calculated results indicate that Eu1-Mn and Eu2-Mn possess higher energy-transfer efficiencies than other Eu-Mn pairs. Under the combined influence of the two effects, single-phased full visible white emission covering from 400 to 700 nm has been realized via the adjustment of solid solution, which makes the fabricated white-light-emitting diode (WLED) possess high color-rendering index (86.9) and R9 (87.2) as well as low correlated color temperature (3947 K). The results show that the 0.2ß-Ca3(PO4)2-0.8Ca9La(PO4)7:0.01Eu2+, 0.20Mn2+ could act as a promising phosphor for single-phased WLEDs. This work will open up a new avenue for tuning the multiple activator sites and energy-transfer efficiencies simultaneously to realize single-phased full visible white emission.

SFTS virus infection in nonhuman primates.

SFTS virus (SFTSV) is a highly pathogenic bunyavirus that causes severe fever with thrombocytopenia syndrome (SFTS), an emerging infectious disease in China. Laboratory mice have been reported to be susceptible to SFTSV infection, but the infection in nonhuman primates has not been investigated. This study is the first to report that, in rhesus macaques, SFTSV does not cause severe symptoms or death but causes fever, thrombocytopenia, leukocytopenia, and increased levels of transaminases and myocardial enzymes in blood. Viremia, virus-specific immunoglobulin M and immunoglobulin G antibodies, and neutralizing antibodies were identified in all infected macaques. Levels of the cytokines interferon γ, eotaxin, tumor necrosis factor α, and macrophage inflammatory protein 1ß were significantly elevated in the blood. Minor pathological lesions were observed in the liver and kidney during the late stages of infection. Overall, SFTSV infection in rhesus macaques resembled mild SFTS in humans.

Frequency of HLA-A 03 associates with HIV-1 infection in a Chinese cohort.

During the early mid-1990s, a number of rural farmers across central China were employed to the unregulated plasmaselling-activity and many of them were infected by HIV-1. However, AIDS progression in the former blood donors (FBDs) is various. The aim of this study is to assess human leukocyte antigen (HLA) class I allele distribution in FBDs and evaluate its association with HIV-1 infection and disease progression. A total of 353 FBDs were enrolled in the cohort including 294 ART naïve HIV-1 seropositive and 59 HIV-1 seronegative age-matched subjects. The viral load and CD4/CD8 T cell counts were assessed in all subjects. Compared with HIV-seropositive group, the frequency of HLA-A 03 in control was significantly higher. After classifying the HLA-B alleles of the subjects according to the presence of Bw4/Bw6 serological epitopes, detrimental effect of HLA Bw6/ Bw6 homozygosity was also confirmed in the HIV-seropositive subjects. This study provides novel evidence on HLA class I allele distribution and association of HLA-A 03 frequency with HIV-1 infection and viremia in the HIV-1 infected FBDs, which may throw light on intervention strategy for the HIV-1 infection and our understanding how host immunity and genetic background affect HIV infection and AIDS progression.

Interleukin-21 up-regulates interleukin-21R expression and interferon gamma production by CD8+ cells in SHIV-infected macaques.

Interleukin-21 (IL-21) is produced primarily by CD4+ T cells and regulates immunity against human/simian immunodeficiency virus (HIV/SIV) infection. Activated CD8+ cells and their secreted interferon-gamma (IFN-γ) are crucial for the control of acute HIV/SIV infection. However, whether IL-21 can regulate IFN-γ production by CD8+ cells remains controversial. Rhesus macaques (RMs, n = 8) were infected with SHIV and the levels of plasma IL-21, IFN-γ and the frequency of peripheral blood activated T cells were measured longitudinally. Following infection with SHIV, the levels of plasma IL-21 and IFN-γ increased, peaked at 17 days postinfection and declined later. Furthermore, IL-21 induced IL-21 receptor (IL-21R) and IFN-γ, perforin, but not granmyze B, expression in CD8+ cells from four selected SHIV-infected RMs. The regulatory effect of IL-21 on CD8+ cell function appeared to be associated with increased levels of STAT3, but not STAT5, phosphorylation in CD8+ cells from SHIV-infected RMs. In parallel, treatment with soluble IL-21R/Fc, an inhibitor of IL-21-induced activation of JAK1/3 and STAT3, abrogated IL-21-induced STAT3 activation and IFN-γ production in CD8+ cells from SHIV-infected RMs in vitro. Our data indicated that IL-21 was a positive regulator of IFN-γ-secreting CD8+ cells and increased the STAT3 phosphorylation, regulating T-cell immunity against acute SHIV infection in RMs. Our findings may provide a new basis for the development of immunotherapies for the control of SHIV/HIV infection.

Circulating IL-21 levels increase during early simian-human immunodeficiency virus infection in macaques.

The cytokine interleukin-21 (IL-21) regulates viral pathogenesis in individuals infected with human and simian immunodeficiency viruses. However, because the time of initial infection with HIV in humans is rarely known, the dynamics of IL-21 production during the first weeks have not been adequately explored. In the present study, we used rhesus macaques to model the first stages of infection. Twenty-two rhesus macaques were infected rectally with simian-human immunodeficiency virus (SHIV)-1157ipd3N4, and for 12 weeks, replication of the virus, the numbers of CD4+ and CD8+ T cells, and the levels of plasma IL-21 were monitored. Our study demonstrated that plasma levels of IL-21 increased during the early phase of SHIV infection when compared with the values observed before inoculation. We conclude that IL-21 has a likely role in the immunopathogenesis of HIV/SIV/SHIV.

Pathogenesis of emerging severe fever with thrombocytopenia syndrome virus in C57/BL6 mouse model.

The discovery of an emerging viral disease, severe fever with thrombocytopenia syndrome (SFTS), caused by SFTS virus (SFTSV), has prompted the need to understand pathogenesis of SFTSV. We are unique in establishing an infectious model of SFTS in C57/BL6 mice, resulting in hallmark symptoms of thrombocytopenia and leukocytopenia. Viral RNA and histopathological changes were identified in the spleen, liver, and kidney. However, viral replication was only found in the spleen, which suggested the spleen to be the principle target organ of SFTSV. Moreover, the number of macrophages and platelets were largely increased in the spleen, and SFTSV colocalized with platelets in cytoplasm of macrophages in the red pulp of the spleen. In vitro cellular assays further revealed that SFTSV adhered to mouse platelets and facilitated the phagocytosis of platelets by mouse primary macrophages, which in combination with in vivo findings, suggests that SFTSV-induced thrombocytopenia is caused by clearance of circulating virus-bound platelets by splenic macrophages. Thus, this study has elucidated the pathogenic mechanisms of thrombocytopenia in a mouse model resembling human SFTS disease.

The effect of orthostatic training in the prevention of vasovagal syncope and its influencing factors.

Recently orthostatic training has been proposed as an effective treatment for vasovagal syncope, even though some patients may relapse. This study was undertaken to assess the effect of orthostatic training on patients with vasovagal syncope and its influencing factors. The study group comprised 125 consecutive patients (51 males and 74 females), aged 40 +/- 19 years, with a history of syncope and a positive head-up tilt test. They were randomized into an orthostatic training group (64 patients) and a no treatment group (controls, 61 patients). The training programme consisted of daily 30-minute sessions of upright standing against a vertical wall 6 days a week for at least 4 weeks. After one year of follow-up, 45 (72.6%) of 62 orthostatic trained patients reported no syncopal recurrence, while only 22 of 61 controls (36.1%, P < 0.05) reported the same. Furthermore, in the training group, the patients with recurrence were older, and the number of syncopal spells in the preceding year was less than in the patients with no recurrence in the same group. Orthostatic training is an effective therapy for the prevention of vasovagal syncope. This kind of therapy was of greater benefit to patients who were younger or experienced frequent spells of syncope.