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IntroductionTraumatic events in early life have a deleterious effect on the development of normal brain developments, which may be a cause of various psychiatric disorders in adulthood. Most prior studies focused on molecular biological aspects, and research on functional changes in neural circuits is still limited. We aimed to elucidate the effect of early life stress on in vivo excitation–inhibition and serotonergic neurotransmission in the adulthood using non-invasive functional molecular imaging (positron emission tomography, PET).MethodsTo compare the effect of stress intensity, early life stress animal models were divided into single trauma (MS) and double trauma groups (MRS). MS was derived from maternal separation, whereas MRS was derived from maternal separation and restraint stress after birth. And to evaluate the stress vulnerability on the sex, we used male and female rats.ResultsThe MRS group showed greater weight loss and more severe depressive/anxiety-like behaviors than the MS and control groups. Corticosterone levels in MRS showed a greater extent of decline than in the MS group; however, there was no significant difference in the change of T3 and T4 between MS and MRS. In the PET, the stress exposure groups showed lower brain uptake for GABAergic, glutamatergic, and serotonergic systems compared with the control group. The excitatory/inhibitory balance, which was derived by dividing glutamate brain uptake into GABAergic uptake, increased as stress intensity increased. Neuronal degeneration in the stress exposure groups was confirmed by immunohistochemistry. In the sex comparison, female showed the greater changes of body weight, corticosterone level, depressive/anxiety-like behavior, and neurotransmission systems than those in male.ConclusionTaken together, we demonstrated that developmental stress induces dysfunction of neurotransmission in vivo, and that females are more vulnerable to stress than males.

PurposeNoninvasively assessing the tumor biology and microenvironment before treatment is greatly important, and glypican-3 (GPC-3) is a new-generation immunotherapy target for hepatocellular carcinoma (HCC). This study investigated the application value of a nomogram based on LI-RADS features, quantitative contrast-enhanced MRI parameters and clinical indicators in the noninvasive preoperative prediction of GPC-3 expression in HCC.Methods and materialsWe retrospectively reviewed 127 patients with pathologically confirmed solitary HCC who underwent Gd-EOB-DTPA MRI examinations and related laboratory tests. Quantitative contrast-enhanced MRI parameters and clinical indicators were collected by an abdominal radiologist, and LI-RADS features were independently assessed and recorded by three trained intermediate- and senior-level radiologists. The pathological and immunohistochemical results of HCC were determined by two senior pathologists. All patients were divided into a training cohort (88 cases) and validation cohort (39 cases). Univariate analysis and multivariate logistic regression were performed to identify independent predictors of GPC-3 expression in HCC, and a nomogram model was established in the training cohort. The performance of the nomogram was assessed by the area under the receiver operating characteristic curve (AUC) and the calibration curve in the training cohort and validation cohort, respectively.ResultsBlood products in mass, nodule-in-nodule architecture, mosaic architecture, contrast enhancement ratio (CER), transition phase lesion-liver parenchyma signal ratio (TP-LNR), and serum ferritin (Fer) were independent predictors of GPC-3 expression, with odds ratios (ORs) of 5.437, 10.682, 5.477, 11.788, 0.028, and 1.005, respectively. Nomogram based on LI-RADS features (blood products in mass, nodule-in-nodule architecture and mosaic architecture), quantitative contrast-enhanced MRI parameters (CER and TP-LNR) and clinical indicators (Fer) for predicting GPC-3 expression in HCC was established successfully. The nomogram showed good discrimination (AUC of 0.925 in the training cohort and 0.908 in the validation cohort) and favorable calibration. The diagnostic sensitivity and specificity were 76.9% and 92.3% in the training cohort, 76.8% and 93.8% in the validation cohort respectively.ConclusionThe nomogram constructed from LI-RADS features, quantitative contrast-enhanced MRI parameters and clinical indicators has high application value, can accurately predict GPC-3 expression in HCC and may help noninvasively identify potential patients for GPC-3 immunotherapy.

Abstract Desmoplastic Small Round Cell Tumor (DSRCT) is a rare and aggressive malignant cancer caused by a chromosomal translocation t(11;22)(p13;q12) that produces an oncogenic transcription factor, EWSR1-WT1. EWSR1-WT1 is essential for the initiation and progression of DSRCT. However, the precise mechanism by which EWSR1-WT1 drives DSRCT oncogenesis remains unresolved. Through our integrative gene expression analysis, we identified Salt Inducible Kinase 1 (SIK1) as a direct target of EWSR1-WT1. SIK1 as a member of the AMPK related kinase is involved in many biological processes. We showed that depletion of SIK1 causes inhibition of tumor cell growth, similar to the growth inhibition observed when EWSR1-WT1 is depleted. We further showed that silencing SIK1 leads to cessation of DNA replication in DSRCT cells and inhibition of tumor growth in vivo. Lastly, combined inhibition of SIK1 and CHEK1with small molecule inhibitors, YKL-05-099 and prexasertib, respectively, showed enhanced cytotoxicity in DSRCT cells compared to inhibition of either kinases alone. This work identified SIK1 as a new potential therapeutic target in DSRCT and the efficacy of SIK1 inhibition may be improved when combined with other intervention strategies.

Abstract Background This study aimed to investigate the changes in facial width according to the ostectomy level of the proximal segment after orthognathic surgery using intraoral vertical ramus osteotomy (IVRO) in patients with mandibular prognathism. Methods The participants included 32 individuals who were diagnosed with class III malocclusion prior to surgery. All participants underwent orthognathic surgery using either version of IVRO. The surgery patients were categorized into two groups depending on the type of proximal bone-segment ostectomy technique used: patients whose osteotomy height was at the level of the mandibular tooth occlusal surface (the mandibular tooth surface–level group) and patients whose osteotomy height was at the level of the mandibular inferior border (the mandibular inferior border–level group). The distances between the mandibular width and soft tissue width at the height of the sigmoid notch, mandibular foramen, and alveolar bone and at the anterior-posterior location of the mandibular condyle, mandibular foramen, and coronoid process were compared between the groups. All data were compared to identify differences between preoperative and postoperative measurements. Results The postoperative change in facial soft tissue width at the intersection of the coronal plane with the coronoid process and the horizontal plane at the height of the mandibular alveolar bone in the group with osteotomy at the level of the mandibular occlusal surface differed significantly from that in the group with osteotomy at the level of the mandibular inferior border, with respective increases (mean ± SD) of 1.3 ± 3.5% and 4.7 ± 5.6%, compared to preoperative measurements (p = 0.050). Conclusions Proximal segment ostectomy at the level of the mandibular occlusal surface must be considered with regard to postoperative facial soft tissue width in vertical ramus osteotomy. Additionally, it is necessary to study the visual effect of the width of the mandible appearing small because of the posterior position of the mandible, even when the mandibular facial width is maintained.

Abstract Background We investigated the patterns and timing of recurrence and death as well as prognostic factors based on clinicopathological and radiological factors in patients who underwent surgical treatment for invasive mucinous adenocarcinoma (IMA). Methods We reviewed clinicopathological findings including spread through air spaces (STAS) and CT findings of IMA such as morphology, solidity, margin, well-defined heterogeneous ground-glass opacity, CT angiogram, and air bronchogram signs from 121 consecutive patients who underwent surgical resection. Prognostic factors for disease-free survival (DFS) and overall survival (OS) were identified. Hazard rate analyses were performed for the survival dynamics. Results T stage (hazard ratio [HR] = 4.102, p = 0.03), N stage (N2 vs. N0, HR = 7.653, p

Travel route recommendation is one of the important research contents in the field of intelligent transportation. Traditional route recommendation methods often recommend routes on the basis of a single factor such as the shortest route or the shortest travel time, while ignoring the influence of urban crowd travel patterns on the route recommendation process. For the problems, in this paper a route recommendation method based on frequent trajectory sequence patterns was proposed. In the data preprocessing stage, the historical trajectory database is used to mine frequent sequence patterns in different periods of city and build a frequent route sequence pattern database. In the path recommendation stage, for a set of candidate paths determined after a given start and end point, the proposed long-short mode weight evaluation model is used to quantitatively evaluate and rank them. Then, the path of which the evaluation value is Top-n is taken out and recommended for the user. The recommendation results were analyzed through four simulation scenarios, and the results show that the recommendation method is reasonable. Compared with the shortest path and test set, the recommended path is better, and it runs faster than traditional path recommendation algorithm.

Abstract Mitochondrial dysfunction is a key element in the progression of Parkinson’s disease (PD). The inefficient operation of the electron transport chain (ETC) impairs energy production and enhances the generation of oxidative stress contributing to the loss of dopaminergic cells in the brain. ATPase inhibitory factor 1 (IF1) is a regulator of mitochondrial energy metabolism. IF1 binds directly to the F1Fo ATP synthase and prevents ATP wasting during compromised energy metabolism. In this study, we found treatment with IF1 protects mitochondria against PD-like insult in vitro. SH-SY5Y cells treated with IF1 were resistant to loss of ATP and mitochondrial inner membrane potential during challenge with rotenone, an inhibitor of complex I in the ETC. We further demonstrated that treatment with IF1 reversed rotenone-induced superoxide production in mitochondria and peroxide accumulation in whole cells. Ultimately, IF1 decreased protein levels of pro-apoptotic Bax, cleaved caspase-3, and cleaved PARP, rescuing SH-SY5Y cells from rotenone-mediated apoptotic death. Administration of IF1 significantly improved the results of pole and hanging tests performed by PD mice expressing human α-synuclein. This indicates that IF1 mitigates PD-associated motor deficit. Together, these findings suggest that IF1 exhibits a neuroprotective effect preventing mitochondrial dysfunction in PD pathology.

Abstract A vertical oxide thin-film transistor was developed with interfacial oxidation for low voltage operation. The gate metal was used as a spacer for the definition of the transistor’s channel as well as the gate electrode. After definition of the vertical side wall, an IGZO (In-Ga-Zn Oxide) layer was deposited, followed by the interfacial oxidation to form a thin gate insulator. Ta was used for the gate material due to the low Gibbs free energy and high dielectric constant of tantalum oxide. A 15 nm tantalum oxide layer was obtained by the interfacial oxidation of Ta at 400 °C under oxygen atmosphere. The thin gate oxide made it possible to operate the transistor under 1 V. The low operation voltage enables low power consumption, which is essential for mobile application.

Dinuclear metal complexes are a promising class of compounds applicable to photoluminescence and catalysis. However, an understanding of the mechanism of the nonradiative decay process of dinuclear metal complexes remains very limited. Herein, the mechanism of the nonradiative decay process of dinuclear iridium(III) complexes (D1 and D2) and their mononuclear iridium(III) complex (M1) is elucidated by using density functional theory (DFT). Our results reveal that the nonradiative decay process occurs on a weak Ir–N bond and therefore results in metal-centered triplet excited (³MC) states. The deactivation pathways connecting the Franck–Condon region and the minimum energy seam of crossing (MESX) were further identified to be the determining step, which is the thermal deactivation pathways of ³MLCT → TS → ³MC→ MESX. The smaller energy barrier from the T1 minimum to the MESX state for D1 (9.48 kcal mol−1) and D2 (8.64 kcal mol−1) relative to that for M1 (10.95 kcal mol−1) plays a key role in observed weak emissions of D1 and D2 in the red region compared to that of M1. Moreover, by introducing the electron-withdrawing Cl atom at the para- or meta-position of the 2-phenylpyrimidine (ppd) moiety, a large energy barrier between the ³MC state and the T1 minimum is obtained. Our work not only provides the possibility of the nonradiative decay process of dinuclear iridium(III) materials, but also paves a promising way for reducing the nonradiative process and developing saturated efficient red dinuclear iridium(III) materials for broader potential application. [ABSTRACT FROM AUTHOR]

In this study, the effects of several geometry factors (fin front angle, clearance, number of fins, and honeycomb cell diameter and depth) on the mass flow function of solid and honeycomb land were studied experimentally. The fin front angle considered in the experiment ranged from 60 to 90 degrees, the number of fins was varied between two and three, and the diameter and depth of the honeycomb cell ranged from 1.33 to 4.00 times and 8.08 to 13.08 times the thickness of the fin tip, respectively. The experimental results showed that the mass flow function decreased as the number of fins increased for the solid land labyrinth seal, and the mass flow function increased as the clearance increased. A fin front angle of 60 degrees was found to have the minimum mass flow function. For the honeycomb land labyrinth seal, the mass flow function decreased as the number of fins increased, and the effect of the cell depth was shown to be insignificant compared to the effect of the cell diameter. The effects of cell diameter and cell depth on the mass flow function depended on the conditions of other variables. In addition, the correlation equations of the mass flow functions of the solid land and honeycomb land labyrinth seals are presented based on the experimental results, which represent the effects of the fin front angle, clearance, pressure ratio, and diameter and depth of the honeycomb cell. The correlation equation for the solid land labyrinth seal had an r2 value of 0.9822, while the correlation equation for honeycomb land had an r2 value of 0.9621.

Blood image intensity has been used to detect erythrocyte sedimentation rate (ESR). However, it does not give information on the biophysical properties of blood samples under continuous ESR. In this study, to quantify mechanical variations of blood under continuous ESR, blood shear stress and blood image intensity were obtained by analyzing blood flows in the capillary channel. A blood sample is loaded into a driving syringe to demonstrate the proposed method. The blood flow rate is set in a periodic on–off pattern. A blood sample is then supplied into a capillary chip, and microscopic blood images are captured at specific intervals. Blood shear stress is quantified from the interface of the bloodstream in the coflowing channel. τ0 is defined as the maximum shear stress obtained at the first period. Simultaneously, ESRτ is then obtained by analyzing temporal variations of blood shear stress for every on period. AII is evaluated by analyzing the temporal variation of blood image intensity for every off period. According to the experimental results, a shorter period of T = 4 min and no air cavity contributes to the high sensitivity of the two indices (ESRτ and AII). The τ0 exhibits substantial differences with respect to hematocrits (i.e., 30–50%) as well as diluents. The ESRτ and AII showed a reciprocal relationship with each other. Three suggested properties represented substantial differences for suspended blood samples (i.e., hardened red blood cells, different concentrations of dextran solution, and fibrinogen). In conclusion, the present method can detect variations in blood samples under continuous ESR effectively.

Atomically thin two-dimensional (2D) hexagonal boron nitride (hBN) has emerged as an essential material for the encapsulation layer in van der Waals heterostructures and efficient deep ultraviolet optoelectronics. This is primarily due to its remarkable physical properties and ultrawide bandgap (close to 6 eV, and even larger in some cases) properties. Color centers in hBN refer to intrinsic vacancies and extrinsic impurities within the 2D crystal lattice, which result in distinct optical properties in the ultraviolet (UV) to near-infrared (IR) range. Furthermore, each color center in hBN exhibits a unique emission spectrum and possesses various spin properties. These characteristics open up possibilities for the development of next-generation optoelectronics and quantum information applications, including room-temperature single-photon sources and quantum sensors. Here, we provide a comprehensive overview of the atomic configuration, optical and quantum properties, and different techniques employed for the formation of color centers in hBN. A deep understanding of color centers in hBN allows for advances in the development of next-generation UV optoelectronic applications, solid-state quantum technologies, and nanophotonics by harnessing the exceptional capabilities offered by hBN color centers.

This paper addresses three significant challenges in controlling robot manipulators: improving response time, minimizing steady-state errors and chattering, and enhancing controller robustness. It also focuses on eliminating the need for computing the robot’s dynamic model and unknown functions, as well as achieving global fixed-time convergence and the prescribed performance for the control system. To achieve these objectives, a fixed-time sliding mode function is designed, which uses transformation errors to achieve prescribed control performance, with adjustments made to the maximum overshoot, convergence time, and tracking errors to keep them within predefined bounds. Additionally, a radial basis function neural network (RBFNN) is used to eliminate the need for knowledge of the robot’s dynamical properties and uncertain terms, which also reduces negative chattering. Finally, a novel fixed-time terminal sliding mode control (TSMC) algorithm is developed for robot manipulators without using their dynamical model. The fixed-time stability of the control system is thoroughly demonstrated by applying Lyapunov criteria and conducting simulations on a robot manipulator to showcase its effectiveness.

Abstract Background Chilling temperature reduces the rate of photosynthesis in plants, which is more pronounced in association with phosphate (Pi) starvation. Previous studies showed that Pi resupply improves recovery of the rate of photosynthesis in plants much better under combination of dual stresses than in non-chilled samples. However, the underlying mechanism remains poorly understood. Results In this study, RNA-seq analysis showed the expression level of 41 photosynthetic genes in plant roots increased under phosphate starvation associated with 4 °C (-P 4 °C) compared to -P 23 °C. Moreover, iron uptake increased significantly in the stem cell niche (SCN) of wild type (WT) roots in -P 4 °C. In contrast, lower iron concentrations were found in SCN of aluminum activated malate transporter 1 (almt1) and its transcription factor, sensitive to protein rhizotoxicity 1 (stop1) mutants under -P 4 °C. The Fe content examined by ICP-MS analysis in -P 4 °C treated almt1 was 98.5 ng/µg, which was only 17% of that of seedlings grown under -P 23 °C. Average plastid number in almt1 root cells under -P 4 °C was less than -P 23 °C. Furthermore, stop1 and almt1 single mutants both exhibited increased primary root elongation than WT under combined stresses. In addition, dark treatment blocked the root elongation phenotype of stop1 and almt1. Conclusions Induction of photosynthetic gene expression and increased iron accumulation in roots is required for plant adjustment to chilling in association with phosphate starvation.

Abstract It is unclear as to whether Wilms’ tumor 1-associated protein (WTAP) promotes or suppresses breast cancer. This immunohistochemistry analysis explored levels of WTAP expression in 347 cases of breast cancer and analyzed the relationship between WTAP expression and the clinicopathological characteristics and prognosis of breast cancer patients. The rate of high WTAP expression was significantly higher in breast cancer tissue than in adjacent normal breast tissue (37.5% vs 0.0%; P

Purpose. To evaluate the prognosis of patients with benign phyllodes tumors (PTs) treated by different surgical methods and to explore the influencing factors of local recurrence. Methods. We retrospectively analyzed 215 benign PTs from 193 patients who underwent surgery at Chinese PLA General Hospital between October 2008 and December 2020. We stratified our analysis according to surgical factors and explored the clinicopathological factors to influence local recurrence. Results. Among 193 patients, a total of 17 (8.8%, 17/193) recurred during follow-up. There were 89 patients in the US-VAE group, of whom 6 (6.7%) recurred; 8 of 57 patients (14%) in the local lumpectomy group recurred, while 3 of 47 patients (6.4%) in the extended lumpectomy group recurred (P=0.252). Multivariate logistic regression analysis showed that tumor diameter, mitosis, and history of breast myoma were independent risk factors for tumor recurrence (P=0.005, P=0.006, and P=0.004, respectively). The intraoperative blood loss, operation time, and scar length of the US-VAE group were shorter than those of the other two groups (P10 mm. Therefore, we recommend that a follow-up observation policy be adopted for patients with unexpected benign PTs, rather than unnecessary open surgical resection. Patients’ maximum tumor diameter, mitosis, and fibroadenoma history were independent predictors for recurrence of benign PTs.

Aptamers have great potential for diagnostics and therapeutics due to high specificity to target molecules. However, studies have shown that aptamers are rapidly distributed and excreted from blood circulation due to nuclease degradation. To overcome this issue and to improve in vivo pharmacokinetic properties, inverted deoxythymidine (idT) incorporation at the end of aptamer has been developed. The goal of this study was to evaluate the biological characterization of 3'-idT modified ErbB2 aptamer and compare with that of unmodified aptamer via nuclear imaging. ErbB2-idT aptamer was labeled with radioisotope F-18 by base-pair hybridization using complementary oligonucleotide platform. The hyErbB2-idT aptamer demonstrated specific binding to targets in a ErbB2 expressing SK-BR-3 and KPL4 cells in vitro. Ex vivo biodistribution and in vivo imaging was studied in KPL4 xenograft bearing Balb/c nu/nu mice. 18F-hyErbB2-idT aptamer had significantly higher retention in the tumor (1.36 ± 0.17%ID/g) than unmodified 18F-hyErbB2 (0.98 ± 0.19%ID/g) or scrambled aptamer (0.79 ± 0.26% ID/g) at 1 h post-injection. 18F-hyErbB2-idT aptamer exhibited relatively slow blood clearance and delayed excretion by the renal and hepatobiliary system than 18F-hyErbB2 aptamer. In vivo PET imaging study showed that 18F-hyErbB2-idT aptamer had more stronger PET signals on KPL4 tumor than 18F-hyErbB2 aptamer. The results of this study demonstrate that attachment of idT at 3'-end of aptamer have a substantial influence on biological stability and extended blood circulation led to enhanced tumor uptake of aptamer.

Many microRNAs (miRNAs) are selectively expressed in mammalian immune cells and have been linked to immune responses in host defense and autoimmune disease. In macrophages, miRNAs regulate cell metabolism by repressing the expression of genes such as transcription factors, enzymes, and metabolism-related molecules, as well as the expression of genes that impact inflammatory responses and phenotype determination. Previous studies showed that miR-22 plays a role in a variety of biological processes, such as cancer cell growth, cell survival, and cell expansion. In CD4 + T cells of inflammatory bowel disease patients, miR-22 is upregulated and regulates inflammasome-mediated responses. However, it has not yet been determined how miR-22 contributes to the activation of innate immune cells. In this study, we identified a mechanism of toll-like receptors- (TLR-) dependent miR-22 induction that regulates the downstream signaling pathway linking inflammatory responses and macrophage polarization. MiR-22 is induced via TLR-signaling, which regulates the induction of Slc2a1 (glucose transporter 1 and Glut1) and Tnfsf9 (tumor necrosis factor 9, 4-1BB ligand, and 4-1BBL) mRNAs that contribute to sustained inflammatory responses and the polarization of macrophages. Our observations support further efforts to explore a potential therapeutic strategy using miR-22 for the modulation of excessive macrophage activation for the treatment of inflammatory diseases.

Carbon-based nanomaterials, including carbon nanotubes, carbon nanospheres, and carbon nanofibers, are becoming a research hotspot due to their unique structure and good mechanical, thermal, electrical, optical, and chemical properties. With the development of material synthesis technology, they can be functionalized and used in various fields such as energy, environment, and biomedicine. In particular, stimuli-responsive carbon-based nanomaterials have stood out in recent years because of their smart behavior. Researchers have applied carbon-based nanomaterials to different disease treatments based on their stimulus-response properties. In this paper, based on stimuli-responsive carbon-based nanomaterials’ morphology, we categorize them into carbon nanotubes, carbon nanospheres, and carbon nanofibers according to their morphology. Then, their applications in probes, bioimaging, tumor therapy, and other fields are discussed. Finally, we address the advantages and disadvantages of carbon-based stimuli-responsive nanomaterials and discuss their future perspective.

The large dynamic and high-speed flight of aerospace vehicle will bring unpredictable conditions to its navigation system, resulting in that its system random noise probability distribution will no longer meet the preconditions of Gaussian distribution preset by the existing filter algorithm, thus reducing the accuracy of the navigation system. So, it is very important to propose an effective method to solve the filter problem of the navigation system in non-Gaussian distribution to improve the accuracy of the navigation system. Therefore, an integrated navigation method of aerospace vehicle based on rank statistics (LRF) has been proposed in this paper. Firstly, based on the flight characteristics of aerospace vehicles, an accurate gravity calculation model has been established to improve the accuracy of system modelling. Then, the state equation and measurement equation of integrated navigation system have been established. In combination with the rank filter algorithm as well as the determined weights, sampling points are calculated and nonlinearly propagated through the transition matrix to achieve an accurate estimation about the predicted values of the state quantities and measurement quantities and the covariance matrix. In turn, it simulates the probability distribution of the system state effectively. Therefore, when the system random noise probability distribution of the aerospace vehicle does not meet the Gaussian distribution due to various interference factors in the actual flight process, the algorithm can simulate the probability distribution of the actual system to the greatest extent, to improve the accuracy of the integrated navigation system and enhance the reliability of the navigation system ultimately.

The Sn-Ag-Cu-based solder paste screen-printing method has primarily been used to fabricate Bi2Te3-based thermoelectric (TE) modules, as Sn-based solder alloys have a low melting temperature (approximately 220℃) and good wettability with Cu electrodes. However, this process may result in uneven solder thickness when the printing pressure is not constant. Therefore, we suggested a novel direct-bonding method between the Bi2Te3-based TE elements and the Cu electrode by electroplating a 100 µm Sn/ 1.3 µm Pd/ 3.5 µm Ni bonding layer onto the Bi2Te3-based TE elements. It was determined that there is a problem with the amount of precipitation and composition depending on the pH change, and that the results may vary depending on the composition of Pd. Thus, double plating layers were formed, Ni/Pd, which were widely commercialized. The Sn/Pd/Ni electroplating was highly reliable, resulting in a bonding strength of 8 MPa between the thermoelectric and Cu electrode components, while the Pd and Ni electroplated layer acted as a diffusion barrier between the Sn layer and the Bi2Te3 TE. This process of electroplating Sn/Pd/Ni onto the Bi2Te3 TE elements presents a novel method for the fabrication of TE modules without using the conventional Sn-alloy-paste screen-printing method.

The alignment of three 2D nanosheets leads to the formation of super-moiré atomic lattices, which can influence the electronic properties of van der Waals structures. Here, the authors report evidence of possible correlated insulating states in doubly-aligned hBN/graphene/hBN heterostructures, in a weak-interaction regime.

Abstract Introduction Since the development of antiretroviral therapy (ART) with TDF plus 3TC plus EFV, this specific regimen has not been studied enough with long-term lipid and uric acid monitoring. Methods A prospective follow-up cohort study was performed. Sixty-one treatment-naive male patients with human immunodeficiency virus (HIV) were divided into three groups based on their baseline CD4+ cell count (26, 12, and 23 patients in the 350 groups, respectively). The lipid and purine metabolism parameters of the patients over 144 weeks were analyzed. Result Within 144 weeks, TG, LDL-c, TC and HDL-c gradually increased, especially TC and HDL-c (P = 0.001, 0.000, respectively). Moreover, the percentages of hyper-cholesterolemia, hyper LDL cholesterolemia, hyper-triglyceridemia and low HDL cholesterolemia also gradually increased, especially low HDL cholesterolemia significantly increased (P = 0.0007). The lower the baseline CD4+ cell counts were, the higher the TG levels and the lower the TC, LDL-c and HDL-c levels were. But there was significant difference of only baseline LDL-c levels between the three groups (P = 0.0457). No significant difference of the UA level and the percentages of hyperuricemia was found between the different follow-up time point groups or between the three CD4+ cell counts groups (all P > 0.05). The risk factors for dyslipidemia included age, anthropometric parameters and follow-up weeks, and for hyperuricemia was virus load. Conclusions Gradual increasing dyslipidemia was found in male patients with human immunodeficiency virus primarily treated with tenofovir plus lamivudine plus efavirenz for 3 years. There-fore lipid metabolism parameters should be closely monitored during long-term ART with the TDF plus 3TC plus EFV regimen.

Abstract Background To investigate the surgical outcomes of implantable collamer lens (ICL) implantation in eyes with residual myopia after primary laser vision correction (LVC) surgeries. Methods This study included patients who underwent ICL implantation and had a history of LVC surgery, including photorefractive keratectomy (PRK) or laser-assisted in situ keratomileusis (LASIK). Visual acuity and refractive error were assessed pre and 3-months postoperatively and the efficacy and safety indices calculated accordingly. Results A total of 30 eyes of 17 patients were included in this study. At 3 months, the mean logMAR uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), and spherical equivalent were − 0.03 ± 0.11 (include logMAR), − 0.04 ± 0.09 (include logMAR), and − 0.06 ± 0.33 diopters (D), respectively. The 3-month Snellen UDVA was better than 20/20 for 83% of eyes, and 97% of eyes showed an unchanged or improved CDVA after surgery. The mean efficacy and safety indices were 1.11 ± 0.22 and 1.13 ± 0.20, respectively. Further, 93 and 100% of eyes were within ±0.5 and ± 1.0 D of the attempted spherical equivalent refraction, respectively. Conclusions ICL implantation in eyes with myopic regression after previous LVC surgery showed safe, effective, and predictable outcomes. Trial registration retrospectively registered.

BackgroundIncreased arterial stiffness is common in patients with diabetes, and inflammation is one of the main causes of increased arterial stiffness. Platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), and monocyte-to-lymphocyte ratio (MLR) are novel inflammatory markers that are reproducible, widely available, and easy to measure, and are associated with low costs. This study sought to investigate the predictive value of these novel inflammatory markers in patients with diabetes having arterial stiffness.MethodsWe retrospectively included inpatients with diabetes mellitus from the Endocrinology Department of the Chengdu Fifth People’s Hospital from June 2021 to May 2022 and collected data on their general information, biochemical indicators, and brachial-ankle pulse wave velocity (baPWV). After propensity matching, the risk relationship between PLR, NLR, and MLR and arterial stiffness was assessed in the recruited patients.ResultsA total of 882 hospitalized patients with diabetes were included in this study and categorized into the low baPWV (507 cases) or high baPWV group (375 cases) based on the baPWV. After propensity matching, there were 180 patients in all in the high and low baPWV groups. Univariate and multivariate logistic regression analyses revealed that high PLR, NLR, and MLR were independently associated with an increased risk of arterial stiffness in patients with diabetes. In the receiver operating characteristic curve analysis, the NLR area under the curve (AUC) was 0.7194 (sensitivity = 84.4%, specificity = 51.1%) when distinguishing low baPWV and high baPWV in patients with diabetes, which was higher than that for PLR AUC (0.6477) and MLR AUC (0.6479), and the combined diagnosis for AUC.ConclusionsNLR was superior to PLR, and MLR and combined diagnosis have certain predictive values that indicate the increase in arterial stiffness in patients with diabetes. These predictive values can help with the early identification of increased arterial stiffness in patients with diabetes.

Introduction: Erythropoietin producing hepatocyte receptor A2 (EphA2) is widely presented in the tumor cells, closely related to tumor cell migration, not cell apoptosis and proliferation. Based on its high expression in castration-resistant prostate cancer (CRPC), we herein develop a CRISPR-Cas9-based genome-editing nanomedicine to target erythropoietin producing hepatocyte receptor A2 for the treatment of castration-resistant prostate cancer.Methods: To this end, TAT was designed to stabilize the distribution of calcium, and then bound to ribonucleoprotein (RNP) to form nanoparticles RNP@CaP-TAT.Results: This nanoparticle has a simple synthesis process with good biocompatible, to achieve the knockout of tumor cells (PC-3) targeting erythropoietin producing hepatocyte receptor A2 gene and to effectively suppress the migration of tumor cells.Discussion: This delivery genome editing system provides a promising gene therapy strategy for the treatment of castration-resistant prostate cancer, showing good potential against castration-resistant prostate cancer tumor metastasis. In addition, it can be extended to other types of cancer with highly heterogeneous gene expression.

Desmoplastic Small Round Cell Tumor (DSRCT) is a rare and aggressive pediatric cancer driven by the EWSR1-WT1 fusion oncogene. Combinations of chemotherapy, radiation and surgery are not curative, and the 5-years survival rate is less than 25%. One potential explanation for refractoriness is the existence of a cancer stem cell (CSC) subpopulation able escape current treatment modalities. However, no study to-date has examined the role of CSCs in DSRCT or established in vitro culture conditions to model this subpopulation. In this study, we investigated the role of stemness markers in DSRCT survival and metastasis, finding that elevated levels of SOX2 and NANOG are associated with worse survival in sarcoma patients and are elevated in metastatic DSRCT tumors. We further develop the first in vitro DSRCT CSC model which forms tumorspheres, expresses increased levels of stemness markers (SOX2, NANOG, KLF4, and OCT4), and resists doxorubicin chemotherapy treatment. This model is an important addition to the DSRCT tool kit and will enable investigation of this critical DSRCT subpopulation. Despite lower sensitivity to chemotherapy, the DSRCT CSC model remained sensitive to knockdown of the EWSR1-WT1 fusion protein, suggesting that future therapies directed against this oncogenic driver have the potential to treat both DSRCT bulk tumor and CSCs.