Oligonucleotide therapies for nonalcoholic steatohepatitis.

Nonalcoholic steatohepatitis (NASH) represents a severe disease subtype of nonalcoholic fatty liver disease (NAFLD) that is thought to be highly associated with systemic metabolic abnormalities. It is characterized by a series of substantial liver damage, including hepatocellular steatosis, inflammation, and fibrosis. The end stage of NASH, in some cases, may result in cirrhosis and hepatocellular carcinoma (HCC). Nowadays a large number of investigations are actively under way to test various therapeutic strategies, including emerging oligonucleotide drugs (e.g., antisense oligonucleotide, small interfering RNA, microRNA, mimic/inhibitor RNA, and small activating RNA) that have shown high potential in treating this fatal liver disease. This article systematically reviews the pathogenesis of NASH/NAFLD, the promising druggable targets proven by current studies in chemical compounds or biological drug development, and the feasibility and limitations of oligonucleotide-based therapeutic approaches under clinical or pre-clinical studies.

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.

Finite-momentum Cooper pairing in proximitized altermagnets.

Finite-momentum Cooper pairing is an unconventional form of superconductivity that is widely believed to require finite magnetization. Altermagnetism is an emerging magnetic phase with highly anisotropic spin-splitting of specific symmetries, but zero net magnetization. Here, we study Cooper pairing in metallic altermagnets connected to conventional s-wave superconductors. Remarkably, we find that the Cooper pairs induced in the altermagnets acquire a finite center-of-mass momentum, despite the zero net magnetization in the system. This anomalous Cooper-pair momentum strongly depends on the propagation direction and exhibits unusual symmetric patterns. Furthermore, it yields several unique features: (i) highly orientation-dependent oscillations in the order parameter, (ii) controllable 0-π transitions in the Josephson supercurrent, (iii) large-oblique-angle Cooper-pair transfer trajectories in junctions parallel with the direction where spin splitting vanishes, and (iv) distinct Fraunhofer patterns in junctions oriented along different directions. Finally, we discuss the implementation of our predictions in candidate materials such as RuO2 and KRu4O8.

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.

Synthesis of α,ω-End Functionalized Polydienes: Allylic-Bearing Heteroleptic Aluminums for Selective Alkylation and Transalkylation in Coordinative Chain Transfer Polymerization.

There are still challenges in the preparation of difunctional stereoregular polydienes, especially for the construction of initiating chain-end functionalization. Coordinative chain transfer polymerization (CCTP) provides a way to achieve the goal but usually requires sophisticated functionalized catalysts as well as expensive chain transfer agents (CTAs). In this work, heteroleptic aluminum with oligo(dienyl) substituents (oligo-Al agents) were readily prepared by living anionic polymerization (LAP) technique. The oligo-Al agents used in Nd-mediated CCTPs of dienes exhibit highly selective alkylation and transalkylation features. Kinetics and transfer efficiency studies using 1 H NMR, 13 C NMR, 1 H-13 C HSQC, and Dosy NMR analyses revealed that the resulting polydienes possess substituents at the initiating chain-end that have transferred from the oligo-Al agents. The functionalization efficiency of the initiating chain-end is up to 99 %, and the molar mass regulation efficiency of heteroleptic aluminum is higher than that of the traditional CTA Ali Bu2 H (0.608 vs. 0.410). Based on the experimental results and density functional theory (DFT) calculations, we propose a mechanism in which allylic-Al acts as an efficient alkylating moiety in catalyst preformation and also as an effective transfer agent in polymerization. Taking advantage of these features, di-functionalized polyisoprene, polybutadiene, and poly(isoprene-co-butadiene) can be facilely synthesized.

An Innovative and Highly Efficient Single-Port Endoscopic Nipple-/Skin-Sparing Mastectomy and Dual-Plane Direct-to-Implant Breast Reconstruction: A Prospective Study from a Single Institution.

BACKGROUND: The difficulty in creating and maintaining a stable workspace of the breast makes endoscopic nipple-/skin-spring mastectomy (E-N/SSM) develop slowly. This study aims to report the preliminary results of a novel endoscopic technique for N/SSM followed by dual-plane direct-to-implant (DP-DTI) breast reconstruction. METHODS: A prospectively maintained database was reviewed that included patients who underwent single-axillary-incision E-N/SSM and DP-DTI breast reconstruction from September 2020 to April 2021 at a single institution by three surgeons. The data were collected prospectively and analyzed to determine the efficacy, feasibility, safety, and esthetic results of the operation, as well as quality of life (QoL). RESULTS: During the study period, a total of 68 E-N/SSM and DP-DTI reconstruction procedures through a single axillary incision were performed in 63 female patients. Among all the procedures, the majority were performed for grade 1-3 ptotic breasts (n =46, 73.0%). During the median follow-up of 26.5 months, the major and minor surgical complication rates were 1.6% (1/63) and 9.5% (6/63), respectively. The cosmetic complication rate was 14.3%. One patient suffered local recurrence 4 months postoperation. The average scores in patient-reported outcomes at 2 years postoperation of satisfaction with breast (66.57), psychosocial well-being (75.93) and sexual well-being (56.29) were not significantly different compared with the baseline, except for physical well-being: chest (69.85). CONCLUSIONS: The proposed procedure for E-N/SSM and DP-DTI breast reconstruction is feasible, time-saving and safe with good outcomes in terms of cosmetic results and QoL and expands the indications of DTI reconstruction to ptotic breasts, making it easier to popularize. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Enhancement of Second-Order Non-Hermitian Skin Effect by Magnetic Fields.

The non-Hermitian skin effect is a unique phenomenon in which an extensive number of eigenstates are localized at the boundaries of a non-Hermitian system. Recent studies show that the non-Hermitian skin effect is significantly suppressed by magnetic fields. In contrast, we demonstrate that the second-order skin effect (SOSE) is robust and can even be enhanced by magnetic fields. Remarkably, SOSE can also be induced by magnetic fields from a trivial non-Hermitian system that does not experience any skin effect at zero field. These properties are intimately related to to the persistence and emergence of topological line gaps in the complex energy spectrum in the presence of magnetic fields. Moreover, we show that a magnetic field can drive a non-Hermitian system from a hybrid skin effect, where the first-order skin effect and SOSE coexist, to pure SOSE. Our results describe a qualitatively new magnetic field behavior of the non-Hermitian skin effect.

Fluctuations in Planar Magnetotransport Due to Tilted Dirac Cones in Topological Materials.

Fluctuations in planar magnetotransport are ubiquitous in topological HgTe structures, in both tensile (topological insulator) and compressively strained layers (Weyl semimetal phase). We show that the common reason for the fluctuations is the presence of tilted Dirac cones combined with the formation of charge puddles. The origin of the tilted Dirac cones is the mix of the Zeeman term due to the in-plane magnetic field and quadratic contributions to the dispersion relation. We develop a network model that mimics the transport of tilted Dirac fermions in the landscape of charge puddles. The model captures the essential features of the experimental data. It should be relevant for the interpretation of planar magnetotransport in a variety of topological and small band gap materials.

Emergent Edge Modes in Shifted Quasi-One-Dimensional Charge Density Waves.

We propose and study a two-dimensional phase of shifted charge density waves (CDW), which is constructed from an array of weakly coupled 1D CDW wires whose phases shift from one wire to the next. We show that the fully gapped bulk CDW has topological properties, characterized by a nonzero Chern number, that imply edge modes within the bulk gap. Remarkably, these edge modes exhibit spectral pseudoflow as a function of position along the edge, and are thus dual to the chiral edge modes of Chern insulators with their spectral flow in momentum space. Furthermore, we show that the CDW edge modes are stable against interwire coupling. Our predictions can be tested experimentally in quasi-1D CDW compounds such as Ta_{2}Se_{8}I.

Patterned cPCDH expression regulates the fine organization of the neocortex.

The neocortex consists of a vast number of diverse neurons that form distinct layers and intricate circuits at the single-cell resolution to support complex brain functions1. Diverse cell-surface molecules are thought to be key for defining neuronal identity, and they mediate interneuronal interactions for structural and functional organization2-6. However, the precise mechanisms that control the fine neuronal organization of the neocortex remain largely unclear. Here, by integrating in-depth single-cell RNA-sequencing analysis, progenitor lineage labelling and mosaic functional analysis, we report that the diverse yet patterned expression of clustered protocadherins (cPCDHs)-the largest subgroup of the cadherin superfamily of cell-adhesion molecules7-regulates the precise spatial arrangement and synaptic connectivity of excitatory neurons in the mouse neocortex. The expression of cPcdh genes in individual neocortical excitatory neurons is diverse yet exhibits distinct composition patterns linked to their developmental origin and spatial positioning. A reduction in functional cPCDH expression causes a lateral clustering of clonally related excitatory neurons originating from the same neural progenitor and a significant increase in synaptic connectivity. By contrast, overexpression of a single cPCDH isoform leads to a lateral dispersion of clonally related excitatory neurons and a considerable decrease in synaptic connectivity. These results suggest that patterned cPCDH expression biases fine spatial and functional organization of individual neocortical excitatory neurons in the mammalian brain.

Segmentation of human aorta using 3D nnU-net-oriented deep learning.

Computed tomography angiography (CTA) has become the main imaging technique for cardiovascular diseases. Before performing the transcatheter aortic valve intervention operation, segmenting images of the aortic sinus and nearby cardiovascular tissue from enhanced images of the human heart is essential for auxiliary diagnosis and guiding doctors to make treatment plans. This paper proposes a nnU-Net (no-new-Net) framework based on deep learning (DL) methods to segment the aorta and the heart tissue near the aortic valve in cardiac CTA images, and verifies its accuracy and effectiveness. A total of 130 sets of cardiac CTA image data (88 training sets, 22 validation sets, and 20 test sets) of different subjects have been used for the study. The advantage of the nnU-Net model is that it can automatically perform preprocessing and data augmentation according to the input image data, can dynamically adjust the network structure and parameter configuration, and has a high model generalization ability. Experimental results show that the DL method based on nnU-Net can accurately and effectively complete the segmentation task of cardiac aorta and cardiac tissue near the root on the cardiac CTA dataset, and achieves an average Dice similarity coefficient of 0.9698 ± 0.0081. The actual inference segmentation effect basically meets the preoperative needs of the clinic. Using the DL method based on the nnU-Net model solves the problems of low accuracy in threshold segmentation, bad segmentation of organs with fuzzy edges, and poor adaptability to different patients' cardiac CTA images. nnU-Net will become an excellent DL technology in cardiac CTA image segmentation tasks.

Doenitin-1: A novel Kunitz family protein with versatile functions during feeding and reproduction of the tick Haemaphysalis doenitzi.

As obligate blood-feeding ectoparasites, ticks secrete a great diversity of antithrombin molecules during feeding. In this study, a novel antithrombin gene named Doenitin-1 was characterized from the tick Haemaphysalis doenitzi. It has an open reading frame size of 426 bp; it encodes 141 amino acids and has a predicted molecular weight of 15.8 kDa. The fibrinogen coagulation test showed that the time of coagulation was increased significantly with increase in rDoenitin-1 protein concentration, and the activated partial thromboplastin time (APTT) and prothrombin time (PT) assays showed that rDoenitin-1 significantly prolonged the coagulation time of APTT, indicating that rDoenitin-1 has an anticoagulant activity in vitro. In addition, rDoenitin-1 presents a significant inhibitory activity in thrombin and cathepsin G. The hemolysis rate of rDoenitin-1 in healthy human blood cells was 4.25%, and no obvious hemolysis activity was observed. The comparison with other life stages shows that the higher expression occurs in adults, and tissue comparison indicated a higher expression in the midgut. The RNAi results indicated that interference of Doenitin-1 significantly reduced the engorgement rate and egg hatchability of H. doenitzi, and that the engorged body weight was slightly reduced. In conclusion, the results suggested that the novel gene Doenitin-1 functions in blood-feeding of H. doenitzi and performs various functions during feeding and reproduction of H. doenitzi. Doenitin-1 may be a potential vaccine candidate for tick control and for developing new antithrombotic drugs in the future.

An antagonistic pleiotropic gene regulates the reproduction and longevity tradeoff.

The antagonistic pleiotropy theory of aging proposes that genes enhancing fitness in early life limit the lifespan, but the molecular evidence remains underexplored. By profiling translatome changes in Caenorhabditis elegans during starvation recovery, we find that an open reading frame (ORF) trl-1 "hidden" within an annotated pseudogene significantly translates upon refeeding. trl-1 mutant animals increase brood sizes but shorten the lifespan and specifically impair germline deficiency­induced longevity. The loss of trl-1 abnormally up-regulates the translation of vitellogenin that produces copious yolk to provision eggs, whereas vitellogenin overexpression is known to reduce the lifespan. We show that the TRL-1 protein undergoes liquid­liquid phase separation (LLPS), through which TRL-1 granules recruit vitellogenin messenger RNA and inhibit its translation. These results indicate that trl-1 functions as an antagonistic pleiotropic gene to regulate the reproduction­longevity tradeoff by optimizing nutrient production for the next generation.

Frequency-dependent polarization of repeating fast radio bursts-implications for their origin.

The polarization of fast radio bursts (FRBs), which are bright astronomical transient phenomena, contains information about their environments. Using wide-band observations with two telescopes, we report polarization measurements of five repeating FRBs and find a trend of lower polarization at lower frequencies. This behavior is modeled as multipath scattering, characterized by a single parameter, σRM, the rotation measure (RM) scatter. Sources with higher σRM have higher RM magnitude and scattering time scales. The two sources with the highest σRM, FRB 20121102A and FRB 20190520B, are associated with compact persistent radio sources. These properties indicate a complex environment near the repeating FRBs, such as a supernova remnant or a pulsar wind nebula, consistent with their having arisen from young stellar populations.

Video-assisted Transaxillary Nipple-sparing Mastectomy and Immediate Implant-based Breast Reconstruction: A Novel and Promising Method.

BACKGROUND: Although video-assisted breast surgery is gaining popularity, endoscopic reconstruction after mastectomy is still facing lots of problems, bring about that endoscopic method has not yet become a standard procedure for breast cancer reconstruction. Here, we introduce a novel surgical technique of video-assisted transaxillary nipple-sparing mastectomy and immediate implant-based breast reconstruction and describe the detailed surgical procedure using this technique. METHODS: Detailed steps of surgical procedure, the patient characteristics and the mean operative time of this new technique were described in this article. All patients were asked to score their satisfaction with their reconstructed breasts preoperatively, 1 month, 3 months, 6 months and 12 months postoperatively using the BREAST-Q. RESULTS: At first, we used our "conventional method" and performed on 10 patients from April 2017 to June 2020; the operative time was 324.80 ± 66.39 minutes. After improving several procedures of the technique, the "optimized method" was performed on 14 cases from July 2020 to November 2020; the operative time decreased to 193.71 ± 28.75 minutes with shortest was 133 minutes; the optimized method was novel and easy to learn and be generalized. Most of the patients were satisfied with the reconstruction results. There was no significant difference between preoperative scores and scores at 3 months, 6 months and 12 months (p = 0.364). Since there is no wound on the breast dome, no obvious postoperative complications were observed except for one patient presented with infection. CONCLUSIONS: This new technique has allowed surgeons to achieve excellent and reproducible outcomes in a single-stage procedure and represents an excellent technique for patients who wish to have a scarless and aesthetically pleasing appearance after mastectomy for breast cancer. This article also highlights the mean operative time (193.71 ± 28.75 minutes) that has been made possible with this new technique. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://www.springer.com/00266 .

Endoscopic-assisted Nipple-sparing Mastectomy with Direct-to-Implant Subpectoral Breast Reconstruction in the Management of Breast Cancer.

Endoscopic-assisted or robotic nipple-sparing mastectomy (E-NSM or R-NSM) with direct-to-implant breast reconstruction is becoming an increasingly popular surgical treatment for breast cancer patients. However, existing surgical methods such as traditional two-dimensional endoscopic-assisted or robot-assisted surgery are time-consuming and expensive. A new innovative three-dimensional videoscope system is efficient but needs special instruments; additionally, the incision over the extramammary region near the anterior axillary line is still too invisible. This study took place from May 2020 to April 2021. This technique is suitable for patients with small- to moderate-sized breasts (C cup size and below; grade 0 to grade I ptotic breasts). We have now performed 30 procedures, including eight bilateral reconstructions. The average operative time (including axillary operation) of a unilateral reconstruction is 179 ± 40.96 minutes, and for bilateral reconstruction, it was 271 ± 45.29 minutes. The median follow-up time was 9.93 months. For the complications, only one patient presented with a mild depigmentation of the nipple and one patient presented with local cellulitis but recovered after oral administration of antibiotics. All patients were satisfied with their postoperative aesthetic outcome. We present a new surgical technique of E-NSM with direct-to-implant subpectoral breast reconstruction to achieve better results.

Super-Resonant Transport of Topological Surface States Subjected to In-Plane Magnetic Fields.

Magnetic oscillations of Dirac surface states of topological insulators are typically expected to be associated with the formation of Landau levels or the Aharonov-Bohm effect. We instead study the conductance of Dirac surface states subjected to an in-plane magnetic field in the presence of a barrier potential. Strikingly, we find that, in the case of large barrier potentials, the surface states exhibit pronounced oscillations in the conductance when varying the magnetic field, in the absence of Landau levels or the Aharonov-Bohm effect. These novel magnetic oscillations are attributed to the emergence of super-resonant transport by tuning the magnetic field, in which many propagating modes cross the barrier with perfect transmission. In the case of small and moderate barrier potentials, we identify a positive magnetoconductance due to the increase of the Fermi surface by tilting the surface Dirac cone. Moreover, we show that for weak magnetic fields, the conductance displays a shifted sinusoidal dependence on the field direction with period π and phase shift determined by the tilting direction with respect to the field direction. Our predictions can be applied to various topological insulators, such as HgTe and Bi_{2}Se_{3}, and provide important insights into exploring and understanding exotic magnetotransport properties of topological surface states.

Chemical composition of essential oils from Thymus mongolicus, Cinnamomum verum, and Origanum vulgare and their acaricidal effects on Haemaphysalis longicornis (Acari: Ixodidae).

Chemical acaricides are mainly used in traditional tick control, which leads to the emergence of tick resistance and concurrently results in environmental pollution. In the present study, the chemical constituents of essential oils (EOs) from Thymus mongolicus, Cinnamomum verum, and Origanum vulgare was analyzed, and their potential application was evaluated to control the vector tick Haemaphysalis longicornis, which is widely distributed over vast areas of Eurasia, Australia, and New Zealand. Gas chromatography-mass spectrometry analysis revealed that the phenols thymol and carvacrol accounted for 34.66% and 75.72% of the EOs of T. mongolicus and O. vulgare, respectively, whereas trans-cinnamaldehyde (49.42%) was the main constituent of C. verum EO. Immersion tests showed that the EOs of C. verum and O. vulgare had significant acaricidal activity against larval H. longicornis, with the 50% lethal concentration (LC50) being 16.07 and 18.02 mg/mL, respectively, and the 95% lethal concentration (LC95) being 120.37 and 130.09 mg/mL, respectively. The EOs of O. vulgare and T. mongolicus showed significant acaricidal activity against unfed adult H. longicornis, with LC50 being 43.50 and 44.21 mg/mL, respectively, and LC95 being 113.66 and 137.99 mg/mL, respectively. The fumigant toxicity test showed significant acaricidal activity of the three EOs against both unfed and engorged nymphal and adult H. longicornis. Enzyme assays revealed that the EOs of both C. verum and O. vulgare significantly inhibited glutathione S-transferase activity (P < 0.05). In contrast, the activities of carboxylesterase and multifunction oxidases were significantly inhibited by EOs extracted from all three plants (P < 0.05). Taken together, these findings suggest that plant EOs may serve as an environment-friendly alternative for synthetic acaricides in future tick control.

Higher-Order Fabry-Pérot Interferometer from Topological Hinge States.

We propose an intrinsic three-dimensional Fabry-Pérot type interferometer, coined "higher-order interferometer," that is based on the chiral hinge states of second-order topological insulators and cannot be mapped to an equivalent two-dimensional setting because of higher-order topological obstructions. Quantum interference patterns in the two-terminal conductance of this interferometer are controllable not only by tuning the strength but also, particularly, by rotating the direction of the magnetic field applied perpendicularly to the transport direction. Remarkably, the conductance exhibits a characteristic beating pattern with multiple frequencies depending on the field strength and direction in a unique fashion. Our novel interferometer thus provides feasible and robust magnetotransport signatures for hinge states of higher-order topological insulators.

High expression levels of centromere protein A plus upregulation of the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin signaling pathway affect chemotherapy response and prognosis in patients with breast cancer.

Centromere proteins (CENPs) are involved in mitosis, and CENP gene expression levels are associated with chemotherapy responses in patients with breast cancer. The present study aimed to examine the roles and underlying mechanisms of the effects of CENP genes on chemotherapy responses and breast cancer prognosis. Using data obtained from the Gene Expression Omnibus (GEO) database, correlation and Cox multivariate regression analyses were used to determine the CENP genes associated with chemotherapy responses and survival in patients with breast cancer. Weighted gene co-expression network and correlation analyses were used to determine the gene modules co-expressed with the identified genes and the differential expression of gene modules associated with the pathological complete response (PCR) and residual disease (RD) subgroups. CENPA, CENPE, CENPF, CENPI, CENPJ and CENPN were associated with a high nuclear grade and low estrogen and progesterone receptor expression levels. In addition, CENPA, CENPB, CENPC and CENPO were independent factors affecting the distant relapse-free survival (DRFS) rates in patients with breast cancer. Patients with high expression levels of CENPA or CENPO exhibited poor prognoses, whereas those with high expression levels of CENPB or CENPC presented with favorable prognoses. For validation between databases, the Cancer Genome Atlas (TCGA) database analysis also revealed that CENPA, CENPB and CENPO exerted similar effects on overall survival. However, according to the multivariate analyses, only CENPA was an independent risk factor associated with DRFS in GEO database. In addition, in the RD subgroup, patients with higher CENPA expression levels had a worse prognosis compared with those with lower CENPA expression levels. Among patients with high expression levels of CENPA, the PI3K/Akt/mTOR pathway was more likely to be activated in the RD compared with the PCR subgroup. The same trend was observed in TCGA data. These results suggested that high CENPA expression levels plus upregulation of the PI3K/Akt/mTOR signaling pathway may affect DRFS in patients with breast cancer.