Correction: Effect of support on hydrogen generation over iron oxides in the chemical looping process.

[This corrects the article DOI: 10.1039/D1RA07210B.].

The evaluation of cystatin protein vaccines based on the stress response of ticks triggered by low-temperature and toxin stress in Haemaphysalis doenitzi.

BACKGROUND: Ticks, which are obligate blood-feeding parasites, transmit a wide range of pathogens during their hematophagic process. Certain enzymes and macromolecules play a crucial role in inhibition of several tick physiological processes, including digestion and reproduction. In the present study, genes encoding type 2 cystatin were cloned and characterized from Haemaphysalis doenitzi, and the potential role of cystatin in tick control was further assessed. RESULTS: Two cystatin genes, HDcyst-1 and HDcyst-2, were successfully cloned from the tick H. doenitzi. Their open reading frames are 390 and 426 base pairs, and the number of coding amino acids are 129 and 141, respectively. In the midgut, salivary glands, Malpighian tubules and ovaries of ticks, the relative expression of HDcyst-1 was higher in the midgut and Malpighian tubules, and HDcyst-2 was higher in the salivary glands of H. doenitzi, respectively. Lipopolysaccharide (LPS) injection and low-temperature stress elevated cystatin expression in ticks. Enzyme-linked immunosorbent assay showed that both rHDcyst-1 and rHDcyst-2 protein vaccines increased antibody levels in immunized rabbits. A vaccination trial in rabbits infected with H. doenitzi showed that both recombinant cystatin proteins significantly reduced tick engorgement weights and egg mass weight, in particular, rHDcyst-1 significantly prolonged tick engorgement time by 1 day and reduced egg hatching rates by 16.9%. In total, rHDcyst-1 and rHDcyst-2 protein vaccinations provided 64.1% and 51.8% protection to adult female ticks, respectively. CONCLUSION: This is the first report on the immunological characterization of the cystatin protein and sequencing of the cystatin gene in H. doenitzi. Cystatin proteins are promising antigens that have the potential to be used as vaccines for infestation of H. doenitzi control. © 2024 Society of Chemical Industry.

Potential clinical significance of ALDH3B1 in auxiliary diagnosis of gastric cancer.

Objective: This research aimed to explore a diagnostic method based on serum ALDH3B1 and to evaluate the clinical diagnostic efficacy in gastric cancer (GC) by comparing it with the traditional GC diagnostic method, the carcinoembryonic protein (CEA) assay. Methods: Serum samples were collected from 70 healthy volunteers and various patients (GC: 76, benign gastric lesions: 20, postoperative: 37, recurrence: 56). The diagnostic efficacy of serum ALDH3B1, CEA and the co-diagnosis were evaluated by receiver operating characteristic curve. ALDH3B1 protein levels were evaluated by western blot. Results: The co-diagnosis of ALDH3B1 and CEA had the highest diagnostic efficacy (area under the curve = 0.841). Conclusion: Serum ALDH3B1 may be used as an auxiliary diagnostic biomarker for GC, and its co-diagnosis with CEA can improve diagnostic efficacy.

The diverse functions of Mu-class Glutathione S-transferase HrGSTm1 during the development of Hyalomma rufipes with a focus on the detoxification metabolism of cyhalothrin.

BACKGROUND: Glutathione S-transferases (GSTs) are a superfamily of multifunctional enzymes in living organisms with metabolic and detoxification functions, which can detoxify exogenous and endogenous compounds and thereby reduce the damage caused by toxic substances to the body. Ticks are obligate blood-sucking ectoparasites that can transmit various pathogens, and the characterization of tick-derived GSTs may help improve current understanding of the molecular mechanism of tick resistance to insecticides. In this study, a novel GST gene, named HrGSTm1, was identified from Hyalomma rufipes. METHODS: Sequence analysis was performed by using bioinformatics techniques. A prokaryotic expression system was used to obtain the recombinant expression protein rHrGSTm1. Detection of spatiotemporal expression patterns of target genes and their response to the toxicity of cyhalothrin on female H. rufipes was performed by using a quantitative PCR platform. The optimal enzymological parameters of rHrGSTm1 using glutathione as substrate were calculated. The antioxidant capacity of the recombinant protein was evaluated by DPPH• (1,1-Diphenyl-2-picrylhydrazyl radical 2,2-Diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl). Knockdown of the HrGSTm1 genes through RNA interference was used to analyze their effects on the physiological parameters of ticks. The changes in HrGSTm1 messenger RNA expression patterns under cypermethrin stress were analyzed. RESULTS: The complementary DNA sequence of HrGSTm1 contained a 672-bp open reading frame, which potentially encoded 223 amino acids. The predicted molecular weight was 25.62 kDa, and the isoelectric point 8.22. HrGSTm1 is a Mu-class GST, belonging to the cytoplasmic GSTs with no signal peptide observed. The Vmax and Km of rHrGSTm1 were 3.367 ± 0.81 uM and 2.208 ± 0.76 uM, respectively, and its activities were dependent on different temperatures and pH conditions; the scavenging rate of rHrGSTm1 to DPPH• reached 76.4% at 1.25 mg/ml. Variable expressions of HrGSTm1 were observed under various treatment periods and in different tissues, with the highest appearing in eggs (analysis of variance [ANOVA], F(2, 9) = 279.9, P < 0.0001) and Malpighian tubules (ANOVA, F(3, 12) = 290.5, P < 0.0001). After knockdown of HrGSTm1, compared with the control group, the mortality in the treatment group was increased by 16.7%, the average oviposition rate decreased by 33.9%, the average engorged body weight decreased by 287.38 mg and egg weight decreased by 127.46 mg, although only the engorged body weight was significantly different (t-test, t(44) = 2.886, P = 0.006). After exposure to three sublethal concentrations (LC05, LC10, LC50) of cyhalothrin, the expression level of HrGSTm1 in the midgut, ovary and salivary gland was upregulated, whereas in Malpighian tubules, it showed a trend of upregulation at first and then downregulation, implying different functions during the detoxification in different tissues. CONCLUSIONS: In this study, a novel GST of the Mu-class was successfully isolated from H. rufipes and systematically subjected to bioinformatic analysis and recombination identification. The variation trend of HrGSTm1 expression level in different tissues suggests that the gene has different detoxification functions in different tissues. The potential function of this gene was analyzed to provide basic research for further investigation of its detoxification mechanism.

Biphasic release of betamethasone from an injectable HA hydrogel implant for alleviating lumbar disc herniation induced sciatica.

Epidural steroid injection (ESI) is a common therapeutic approach for managing sciatica caused by lumbar disc herniation (LDH). However, the short duration of therapeutic efficacy and the need for repeated injections pose challenges in LDH treatment. The development of a controlled delivery system capable of prolonging the effectiveness of ESI and reducing the frequency of injections, is highly significant in LDH clinical practice. In this study, we utilized a thiol-ene click chemistry to create a series of injectable hyaluronic acid (HA) based release systems loaded with diphasic betamethasone, including betamethasone dipropionate (BD) and betamethasone 21-phosphate disodium (BP) (BD/BP@HA). BD/BP@HA hydrogel implants demonstrated biocompatibility and biodegradability to matched neuronal tissues, avoiding artificial compression following injection. The sustained release of betamethasone from BD/BP@HA hydrogels effectively inhibited both acute and chronic neuroinflammation by suppressing the nuclear factor kappa-B (NF-κB) pathway. In a mouse model of LDH, the epidural administration of BD/BP@HA efficiently alleviated LDH-induced sciatica for at least 10 days by inhibiting the activation of macrophages and microglia in dorsal root ganglion and spinal dorsal horn, respectively. The newly developed HA hydrogels represent a valuable platform for achieving sustained drug release. Additionally, we provide a simple paradigm for fabricating BD/BP@HA for epidural injection, demonstrating greater and sustained efficiency in alleviating LDH-induced sciatica compared to traditional ESI and displaying potentials for clinical translation. This system has the potential to revolutionize drug delivery for co-delivery of both soluble and insoluble drugs, thereby making a significant impact in the pharmaceutical industry. STATEMENT OF SIGNIFICANCE: Lumbar disc herniation (LDH) is a common degenerative disorder leading to sciatica and spine surgery. Although epidural steroid injection (ESI) is routinely used to alleviate sciatica, the efficacy is short and repeated injections are required. There remains challenging to prolong the efficacy of ESI. Herein, an injectable hyaluronic acid (HA) hydrogel implant by crosslinking acrylated-modified HA (HA-A) with thiol-modified HA (HA-SH) was designed to achieve a biphasic release of betamethasone. The hydrogel showed biocompatibility and biodegradability to match neuronal tissues. Notably, compared to traditional ESI, the hydrogel better alleviated sciatica in vivo by synergistically inhibiting the neuroinflammation in central and peripheral nervous systems. We anticipate the injectable HA hydrogel implant has the potential for clinical translation in treating LDH-induced sciatica.

A second-generation M1-polarized CAR macrophage with antitumor efficacy.

Chimeric antigen receptor (CAR) T cell therapies have successfully treated hematological malignancies. Macrophages have also gained attention as an immunotherapy owing to their immunomodulatory capacity and ability to infiltrate solid tumors and phagocytize tumor cells. The first-generation CD3ζ-based CAR-macrophages could phagocytose tumor cells in an antigen-dependent manner. Here we engineered induced pluripotent stem cell-derived macrophages (iMACs) with toll-like receptor 4 intracellular toll/IL-1R (TIR) domain-containing CARs resulting in a markedly enhanced antitumor effect over first-generation CAR-macrophages. Moreover, the design of a tandem CD3ζ-TIR dual signaling CAR endows iMACs with both target engulfment capacity and antigen-dependent M1 polarization and M2 resistance in a nuclear factor kappa B (NF-κB)-dependent manner, as well as the capacity to modulate the tumor microenvironment. We also outline a mechanism of tumor cell elimination by CAR-induced efferocytosis against tumor cell apoptotic bodies. Taken together, we provide a second-generation CAR-iMAC with an ability for orthogonal phagocytosis and polarization and superior antitumor functions in treating solid tumors relative to first-generation CAR-macrophages.

HK2 in microglia and macrophages contribute to the development of neuropathic pain.

Neuropathic pain is a complex pain condition accompanied by prominent neuroinflammation involving activation of both central and peripheral immune cells. Metabolic switch to glycolysis is an important feature of activated immune cells. Hexokinase 2 (HK2), a key glycolytic enzyme enriched in microglia, has recently been shown important in regulating microglial functions. Whether and how HK2 is involved in neuropathic pain-related neuroinflammation remains unknown. Using a HK2-tdTomato reporter line, we found that HK2 was prominently elevated in spinal microglia. Pharmacological inhibition of HK2 effectively alleviated nerve injury-induced acute mechanical pain. However, selective ablation of Hk2 in microglia reduced microgliosis in the spinal dorsal horn (SDH) with little analgesic effects. Further analyses showed that nerve injury also significantly induced HK2 expression in dorsal root ganglion (DRG) macrophages. Deletion of Hk2 in myeloid cells, including both DRG macrophages and spinal microglia, led to the alleviation of mechanical pain during the first week after injury, along with attenuated microgliosis in the ipsilateral SDH, macrophage proliferation in DRGs, and suppressed inflammatory responses in DRGs. These data suggest that HK2 plays an important role in regulating neuropathic pain-related immune cell responses at acute phase and that HK2 contributes to neuropathic pain onset primarily through peripheral monocytes and DRG macrophages rather than spinal microglia.

Adenosine A2A receptor and glia.

The adenosine A2A receptor (A2AR) is abundantly expressed in the brain, including both neurons and glial cells. While the expression of A2AR is relative low in glia, its levels elevate robustly in astrocytes and microglia under pathological conditions. Elevated A2AR appears to play a detrimental role in a number of disease states, by promoting neuroinflammation and astrocytic reaction to contribute to the progression of neurodegenerative and psychiatric diseases.

Microglia and macrophages contribute to the development and maintenance of sciatica in lumbar disc herniation.

ABSTRACT: Lumbar disc herniation (LDH) is a major cause of sciatica. Emerging evidence indicated that inflammation induced by the herniated nucleus pulposus (NP) tissues plays a major role in the pathogenesis of sciatica. However, the underlying mechanisms are still elusive. Although microglia and macrophages have been implicated in nerve injury-induced neuropathic pain, their roles in LDH-induced sciatica largely remain unknown. This study successfully established and modified a mouse model of LDH. We found that nerve root compression using degenerated NP tissues can initiate remarkable and persistent sciatica, with increased and prolonged macrophage infiltration in dorsal root ganglia (DRG) and significant activation of microglia in the spinal dorsal horn. Instead, compression of the nerve root with nondegenerated NP tissues only led to transient sciatica, with transient infiltration and activation of macrophages and microglia. Moreover, continuous treatment of PLX5622, a specific colony-stimulating factor 1 receptor antagonist, ablated both macrophages and microglia, which effectively alleviated LDH-induced sciatica. However, mechanical allodynia reoccurred along with the repopulation of macrophages and microglia after the withdrawal of PLX5622. Using RNA sequencing analysis, the current study depicted transcriptional profile changes of DRG after LDH and identified several macrophage-related potential target candidates. Our results suggested that microglia and macrophages may play an essential role in the development and maintenance of LDH-induced sciatica. Targeting microglia and macrophages may be a promising treatment for chronic LDH-induced sciatica.

Endogenous Stimuli-Responsive Autonomous Separation of Dual-Targeting DNA Guided Missile from Nanospacecraft for Intelligent Targeted Cancer Therapy.

Most conventional chemotherapeutics indiscriminately kill both cancerous and healthy cells and cause toxic side effects, limiting the maximum tolerated dose and thereby compromising therapeutic efficacy. To address this challenge, here dual-targeting intelligent DNA guided missile (GM)-integrated nanospacecraft (NSC) (abbreviated as GM-NSC) is demonstrated for staged chemotherapeutic drug delivery exclusively into cancer cells and then mitochondria (not into healthy cells). GM-NSC is essentially a core/shell nanocomposite composed of gold nanoparticles (AuNPs) surrounded by a high-density multilayer DNA crown that is self-assembled from DNA tetrahedral units (DNA Tetra) in a highly ordered manner. Each tetrahedral structural unit is equipped with three functional components: a cancer cell-targeting aptamer pointing toward the outside environment, a hidden mitochondria-targeting triphenylphosphonium (TPP), and an explosive bolt (E-bolt). GM-NSC can remain intact in fetal bovine serum solution over 12 h and has 53-fold improved systemic stability. Each GM-NSC accommodates 1250 anticancer doxorubicin (Dox), achieving a 48-63-fold improved drug payload capacity. When systemically administrated into a tumor-bearing xenograft murine model, Dox-loaded GM-NSC enters into tumor sites with 18-fold improved specificity followed by autonomous separation of GMs from the NSC core and specific mitochondrial accumulation due to the explosion of E-bolt upon stimuli of endogenous miRNAs. About 80% of Dox uptaken is transferred into mitochondria and induces mitochondria-mediated apoptosis. As a result, the growth of malignant tumor is almost 100% inhibited without detectable toxicity to healthy tissues. Due to the desirable systemic stability, good biocompatibility, high cargo loading capability, satisfactory in vivo biodistribution, and therapeutic efficacy without adverse effects, intelligible GM-NSC is expected to become an alternative drug delivery system for precision cancer therapy.

Comprehensive Analysis Revealed the Potential Implications of m6A Regulators in Lung Adenocarcinoma.

Background: The biological significance of RNA N6-methyladenosine (m6A) decoration in tumorigenicity and progression has been highlighted in recent studies, but whether m6A modification plays a potential role in tumor microenvironment (TME) formation and immune regulation in lung adenocarcinoma (LUAD) remains unclear. Methods: m6A modification features were evaluated by analyzing the multi-omics features of 17 m6A regulators in over 1900 LUAD samples, and at the same time, the correlation between these modification patterns and TME characteristics was analyzed. An m6A score signature-based principal component analysis (PCA) algorithm was constructed to assess the prognosis and responses of individual patients to immunotherapeutic and targeted therapies. Results: Three different m6A modification patterns were determined in 1901 LUAD samples, which were found to be related to diverse clinical outcomes via different biological pathways. Based on the m6A score extracted from the m6A-associated signature genes, LUAD patients were separated into high- and low-m6A score groups. It was discovered that patients with high m6A scores had longer survival, lower tumor mutation loads, and low PD-L1/PDCD1/CTLA4/TAG3 expression level. In addition, LUAD patients with high m6A scores displayed lower IC50 to some targeted drugs, including nilotinib, erlotinib, imatinib, and lapatinib. Conclusion: m6A modification was significantly associated with the TME and clinical outcomes. These findings may help gain more insights into the role of m6A decoration in the molecular mechanism of LUAD, thus facilitating the development of more effective personalized treatment strategies.

Significance of a tumor microenvironment-mediated P65-miR-30a-5p-BCL2L11 amplification loop in multiple myeloma.

Despite significant progress in the treatment of myeloma, multiple myeloma (MM) remains an incurable hematological malignancy due to cell adhesion-mediated drug resistance (CAM-DR) phenotype. However, data on the molecular mechanisms underlying the CAM-DR remains scanty. Here, we identified a miRNA-mRNA regulatory network in myeloma cells that are directly adherent to bone marrow stromal cells (BMSCs). Our data showed that the BMSCs up-regulated miR-30a-5p and down-regulated BCL2L11 at both mRNA and protein level in the myeloma cells. Besides, luciferase reporter genes demonstrated direct interaction between miR-30a-5p and BCL2L11 gene. Moreover, the BMSCs activated NF-ΚB signaling pathway in myeloma cells and the NF-κB P65 was shown to directly bind the miR-30a-5p promoter region. Moreover, suppression of the miR-30a-5p or upregulation of the BCL2L11 promoted apoptosis of the myeloma cells independent of the BMSCs, thus suggesting clinical significance of miR-30a-5p inhibitor and PLBCL2L11 plasmid in CAM-DR. Together, our data demonstrated the role of P65-miR-30a-5p-BCL2L11 loop in CAM-DR myeloma cells. These findings give new insights into the role of tumor microenvironment in the treatment of patients with myeloma.

Dynamics of a disinhibitory prefrontal microcircuit in controlling social competition.

Social competition plays a pivotal role in determining individuals' social status. While the dorsomedial prefrontal cortex (dmPFC) is essential in regulating social competition, it remains unclear how information is processed within its local networks. Here, by applying optogenetic and chemogenetic manipulations in a dominance tube test, we reveal that, in accordance with pyramidal (PYR) neuron activation, excitation of the vasoactive intestinal polypeptide (VIP) or inhibition of the parvalbumin (PV) interneurons induces winning. The winning behavior is associated with sequential calcium activities initiated by VIP and followed by PYR and PV neurons. Using miniature two-photon microscopic (MTPM) and optrode recordings in awake mice, we show that VIP stimulation directly leads to a two-phased activity pattern of both PYR and PV neurons-rapid suppression followed by activation. The delayed activation of PV implies an embedded feedback tuning. This disinhibitory VIP-PV-PYR motif forms the core of a dmPFC microcircuit to control social competition.

Effect of Sc on the Hot Cracking Properties of 7xxx Aluminum Alloy and the Microstructure of Squeeze Castings.

In this paper, the effect of adding the refiner Sc to the high Zn/Mg ratio 7xxx series aluminum alloy melt on the hot tearing performance, microstructure, and mechanical properties of the alloy is studied. The hot tearing performance test (CRC) method is used to evaluate the hot tearing performance of the alloy. The squeeze casting process was used to form solid cylindrical parts to analyze the structure and properties of the alloy. This study shows that the hot cracking sensitivity of the alloy after the addition of the refiner Sc is significantly reduced. The ingot grain size is significantly reduced, and the average grain size is reduced from about 86 µm to about 53 µm. While the mechanical properties are significantly improved, and the tensile strength reduced from 552 MPa is increased to 571 MPa, and the elongation rate is increased from 11% to 14%.

Functional Outcome and Inflammatory Response of Patients with Extra-Articular Distal Humeral Fractures following Implantation of Anatomically Precontoured Locking Compression Plates through a Posterior Approach.

Distal humeral fractures are challenging injuries to surgically correct and account for up to 2% of all adult fractures. Surgical management of extra-articular distal humeral fractures is challenging considering surgical approach, implant selection, and position of the implant owing to the availability of different precontoured implants and plate configurations. Anatomically precontoured locking compression plates (APLCPs) allow the placement of angular stable screws right underneath the reduced joint surface fragments. To date, there is a lack of evidence supporting its superiority to conventional locking plate osteosynthesis (LPO) in treating extra-articular distal humeral fractures. The objective of the study is to evaluate the efficacy and safety of APLCPs in the treatment of extra-articular distal humeral fractures. A total of 100 patients diagnosed with humeral fractures and receiving treatments in our hospital between May 2018 and May 2020 fulfilled inclusion and exclusion criteria and were randomly assigned to LPO and APLCP groups according to the odd-even of the order of hospital admission, 50 cases per groups. Clinical endpoints were assessed including operation time; in-bed time; length of hospital stay; volume of intraoperative blood loss; VSA scores before and 24, 48, and 72 h after surgery; MEPS scores before and 3, 6, and 12 months after surgery; range of motion, flexion, and extension of the elbow; serum levels of CK, CRP, and IL-6; and incidence of complications after surgery. It was found that the APLCP group exhibited shortened operation time and in-bed time, decreased length of hospital stay, and reduced volume of intraoperative blood loss compared to the LPO group (all P < 0.001). The two groups had declined VSA scores concomitant with increased MEPS scores after surgery in a time-dependent manner (P < 0.001). Notably, the VSA scores in the APLCP group were all lower than those in the LPO group at indicated time points (24, 48, and 72 h) after surgery (P < 0.001). Besides, the MEPS scores in the APLCP group were all higher than those in the LPO group at indicated time points (3, 6, and 12 months) after surgery (P < 0.001). It was revealed that the patients receiving extra-articular distal humeral APLCP through posterior approaches exhibited greater ranges of motion, flexion, and extension of the elbow than those receiving LPO after surgery (P < 0.001). The patients receiving extra-articular distal humeral APLCP through posterior approaches exhibited lower serum levels of IL-6, CRP, and CK than those receiving LPO after surgery (IL-6: P=0.007, CRP: P=0.001, CK: P=0.001). The APLCP had a lower total incidence rate of complication than the LPO group (48.00% vs. 18.00%, P=0.003). In conclusion, these data support the notion that the implantation of anatomically precontoured APLCP through a posterior approach allows for improved functional outcomes and attenuated inflammatory response and prevents the incidence of postoperative complications compared to conventional LPO for internal fixation of extra-articular distal humeral fractures.

cFos-ANAB: A cFos-based Web Tool for Exploring Activated Neurons and Associated Behaviors.

cFos is one of the most widely-studied genes in the field of neuroscience. Currently, there is no systematic database focusing on cFos in neuroscience. We developed a curated database-cFos-ANAB-a cFos-based web tool for exploring activated neurons and associated behaviors in rats and mice, comprising 398 brain nuclei and sub-nuclei, and five associated behaviors: pain, fear, feeding, aggression, and sexual behavior. Direct relationships among behaviors and nuclei (even cell types) under specific stimulating conditions were constructed based on cFos expression profiles extracted from original publications. Moreover, overlapping nuclei and sub-nuclei with potentially complex functions among different associated behaviors were emphasized, leading to results serving as important clues to the development of valid hypotheses for exploring as yet unknown circuits. Using the analysis function of cFos-ANAB, multi-layered pictures of networks and their relationships can quickly be explored depending on users' purposes. These features provide a useful tool and good reference for early exploration in neuroscience. The cFos-ANAB database is available at www.cfos-db.net .

Clinical outcome of femoral neck system versus cannulated compression screws for fixation of femoral neck fracture in younger patients.

BACKGROUND: The clinical outcome of a new fixation device (femoral neck system, FNS) for femoral neck fractures remains unclear. The main purpose of this study was to evaluate two different internal fixation methods for the treatment of femoral neck fractures in patients aged under 60 years. METHODS: We retrospectively studied patients who underwent internal fixation surgery in our hospital for femoral neck fractures between January 2017 and January 2020. Cannulated compression screws (CCS) and FNS groups were divided according to different internal fixation methods. General data (such as sex, age, body mass index, type of fracture) of all patienFemoral neck shorteningts were collected, and joint function was evaluated using the Harris Hip Score (HHS) before and 1 year after surgery. We recorded related surgical complications, including femoral head necrosis, nonunion, and femoral neck shortening. RESULTS: There were no significant differences in age, sex, or body mass index between the two groups. There was no statistical difference in HHSs between the two groups before surgery. Patients who underwent FNS treatment had longer surgery time (79.75 ± 26.35 min vs. 64.58 ± 18.56 min, p = 0.031) and more blood loss (69.45 ± 50.47 mL vs. 23.71 ± 28.13 mL, p < 0.001). The degree of femoral neck shortening in the FNS group was significantly lower than that in the CCS group (10.0% vs 37.5%, p = 0.036). Regarding postoperative complications, there was no statistical difference in the incidence of femoral head necrosis and fracture nonunion between the two groups. CONCLUSION: Patients younger than 60 with femoral neck fractures can obtain satisfactory clinical results with CCS or FNS treatment. FNS has excellent biomechanical properties and shows significantly higher overall construct stability.

Programmably tiling rigidified DNA brick on gold nanoparticle as multi-functional shell for cancer-targeted delivery of siRNAs.

Small interfering RNA (siRNA) is an effective therapeutic to regulate the expression of target genes in vitro and in vivo. Constructing a siRNA delivery system with high serum stability, especially responsive to endogenous stimuli, remains technically challenging. Herein we develop anti-degradation Y-shaped backbone-rigidified triangular DNA bricks with sticky ends (sticky-YTDBs) and tile them onto a siRNA-packaged gold nanoparticle in a programmed fashion, forming a multi-functional three-dimensional (3D) DNA shell. After aptamers are arranged on the exterior surface, a biocompatible siRNA-encapsulated core/shell nanoparticle, siRNA/Ap-CS, is achieved. SiRNAs are internally encapsulated in a 3D DNA shell and are thus protected from enzymatic degradation by the outermost layer of YTDB. The siRNAs can be released by endogenous miRNA and execute gene silencing within tumor cells, causing cell apoptosis higher than Lipo3000/siRNA formulation. In vivo treatment shows that tumor growth is completely (100%) inhibited, demonstrating unique opportunities for next-generation anticancer-drug carriers for targeted cancer therapies.

A novel defensin-like peptide contributing to antimicrobial and antioxidant capacity of the tick Dermacentor silvarum (Acari: Ixodidae).

Defensins are the most diverse groups of antimicrobial peptides in invertebrate animals. In ticks, defensins show great potential as targets for tick control, and display future prospect for therapeutic drug development. In the present study, a novel defensin-like gene (Ds-defensin) contributing to the antimicrobial and antioxidant capacity of the tick Dermacentor silvarum was characterized. The full-length of the Ds-defensin gene was 382 bp, which displayed tissue-specific expression and was highly abundant in the salivary glands and carcasses of the adults. It encodes a 71-amino acid defensin-like protein, and the protein precursor is characterized by a 22-amino acid signal peptide and a 34-amino acid mature peptide. The peptide displayed potent activity against most of the tested gram-positive bacteria, including Staphylococcus aureus, S. carnosus and Nocardia asteroides, and one tested gram-negative bacterium, Psychrobacter faecalis. Scanning electron microscopy revealed that the cell wall and surface of treated bacteria became rough and gradually formed pores after a 30-min exposure to the Ds-defensin peptide. Additionally, the peptide also showed significant antioxidant capacity. The above results implied that the defensin-like peptide may play an important role in tick defense and the interaction with microorganisms.