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Background Thrombocytopenia is commonly observed in patients with sepsis and is an independent risk factor for poor prognosis. However, the changes of platelet count caused by different pathogens can vary significantly. Our study aims to evaluate the quantitative changes in platelet count in response to various pathogens.Material and Methods We retrospectively analysed data of 3044 patients with sepsis from Medical Information Mart for Intensive Care (MIMIC, 2008–2019) database and prospectively collected data of 364 patients with sepsis from our local cohort of the Shandong Bloodstream Infection and Sepsis Collaboration Study (SBISC, 2020–2022). Propensity score matching (PSM) was employed to control for baseline differences in variables, except for the causative pathogen.Results Multivariate logistic analyses of both original and PSM populations identified Candida, Escherichia, Klebsiella, and Serratia species posing a higher risk for thrombocytopenia compared to others. Restricted cubic spline (RCS) curves showed L- or U-shaped associations between platelet count and 28-mortality with various cut-off values among different pathogens: ranging from 96 × 109/L in Candida species − 190 × 109/L in Klebsiella species.Conclusion Our present findings indicate a pathogen-specific effect on platelet count, highlighting the importance of monitoring thrombocytopenia in patients infected with above microorganisms. Clinicians need to consider pathogen-specific thresholds when intervene on platelet count.

BackgroundSevere community-acquired pneumonia (SCAP) is the main cause of mortality in immunocompromised patients. Compared with conventional microbiological tests (CMT), metagenomic next-generation sequencing (mNGS) can quickly and simultaneously detect a wide array of bacteria, viruses, and fungi in an unbiased manner. It is increasingly used for severe respiratory infectious diseases, especially for immunocompromised patients. However, the effects of mNGS-based antimicrobial treatment procedures on clinical outcomes in immunocompromised patients with SCAP have not been evaluated.Methods/DesignThe MATESHIP study is a prospective, multicenter, parallel-group, open-label, randomized controlled trial from 20 ICUs in university hospitals and academic teaching hospitals across Shandong Province, China. We will enroll 342 immunocompromised patients with early onset SCAP who are admitted to an intensive care unit (ICU). Participants will be randomly allocated to an mNGS-guided treatment group or a conventional treatment group (guided by CMT), according to centrally computer-based block randomization stratified by participating centers. Participants will undergo CMT tests using appropriate lower respiratory tract (LRT) and other necessary specimens, with or without mNGS tests using LRT specimens. The primary outcomes will be: (1) The relative change in Sequential Organ Failure Assessment (SOFA) score from randomization to day 5, day 7, day 10, or the day of ICU discharge/death; and (2) the consumption of antimicrobial agents during ICU stay (expressed as defined daily doses). The secondary outcome measures will be: days from randomization to initiation of definitive antimicrobial treatment; overall antimicrobial agent use and cost; total cost of hospitalization; length of ICU stay; 28- and 90-day mortality; and clinical cure rate. This study hypothesizes that mNGS-guided treatment will decrease the degree of organ dysfunction/failure, the consumption of antimicrobial agents, and mortality, while the cure rate will be increased, and the time to initiation of appropriate therapy will be advanced.DiscussionThe MATESHIP study will evaluate for the first time whether mNGS-guided antimicrobial therapy improves the outcomes of SCAP in an immunocompromised population, and provide high-level evidence on the application of mNGS in the management of this population.Clinical Trial Registration[ClinicalTrials.gov], identifier [NCT05290454].

Context Qingluoyin (QLY) is a traditional Chinese medicine (TCM) formula which has been used in treating human rheumatoid arthritis (RA) for years in China. Objective This study investigates the effect of QLY granules on adjuvant arthritis (AA) and the possible mechanism. Materials and methods Sprague-Dawley (SD) rats were injected with Complete Freund’s adjuvant (CFA) to induce the AA model. After the onset of arthritis, rats received intragastric administrations of the QLY granules (1.35, 2.70, and 5.40 g/kg) or Tripterygium glycosides (TG) tablets (positive drug, 10 mg/kg) for 14 d. After 28 d immunization, the symptoms, inflammatory parameters and molecular mechanisms were investigated. Results In the QLY granule (1.35, 2.70, and 5.40 g/kg) therapy groups, the arthritis index decreased to 6.30 ± 2.06, 5.80 ± 1.55, 5.30 ± 1.16 compared with the model (9.00 ± 3.01), paw swelling decreased to 1.56 ± 0.40, 1.28 ± 0.38, 1.12 ± 0.41 mL compared with the model (2.22 ± 0.73 mL). QLY granules (1.35, 2.70 and 5.40 g/kg) significantly reduced the thymus and the spleen indexes, inhibited the production of pro-inflammatory cytokines, and alleviated the pathological changes of joints compared with the model group. Furthermore, the treatment of QLY granules (2.70 and 5.40 g/kg) markedly inhibited CXCL12, CXCR4 (in spleen and synovium) and p-NF-κB p65 (in synovium) protein expression of AA rats. Conclusions QLY granules have obvious therapeutic effects on AA rats, which may be associated with downregulating the CXCL12/CXCR4-NF-κB signalling pathway. QLY granules can be used as a candidate for the treatment of RA, which deserves further study.

Background. The present work aims at formulating the melatonin-loaded nanoparticles (MTNPs) exhibiting the controlled-release and pH-sensitivity to repurpose the use of melatonin in the treatment of depressive-like behaviors and hypothalamus-pituitary-adrenal (HPA) axis dysregulation. Methods. MTNPs were characterized for the size, drug incorporation, and in vitro release in the different pH environments. Its merits were in vivo tested on the pinealectomized rats presenting the depressive-like behaviors and the abnormal HPA axis activity by calculating the improvement on saccharin preference, swimming immobility time, and the negative feedback of HPA axis. Results. Results revealed that MTNPs showed nanometer size, 15.77% of drug loading, 33.82% of encapsulation efficiency, the different controlled-release profiles in different pH environments (pH 1.2, pH 6.8, and pH 7.4), more sensitivity release in simulated intestinal fluid (pH 7.4) and blood (pH 6.8), and less sensitivity release in simulated gastric fluid (pH 1.2). Furthermore, MTNPs displayed better antidepressant actions in reducing the immobility time of forced swimming test, increasing the preference for saccharin, and sensitizing the blunt negative feedback of HPA axis, when compared to the free melatonin. Conclusions. The controlled-release nanoparticles is shown to be an effective improvement on the dosage form for melatonin, which is worthy of futuristic and complete evaluation.

Aim. The aim of this study was to evaluate the levels of kisspeptin and AMH in children with PT or CPP or controls to provide a reference for diagnosis and prognosis. Methods. 38 Chinese children with central precocious puberty (CPP), 38 Chinese children with premature thelarche (PT), and 75 controls were recruited. Results. In CPP girls, AMH levels decreased significantly compared to control girls at T2 stage. Compared with the PT and control groups, AMH is the lowest in girls in the CPP group at T3 stage. Kisspeptin decreased significantly in girls in the PT group and increased significantly in girls in the control group from T2 stage to T3 stage. At T3 stage, kisspeptin was significantly higher in girls in the CPP and control groups than in the PT group. In the control group, kisspeptin was significantly higher in boys than in girls at T2 stage. AMH and height were negatively correlated in the girls group. Conclusions. Kisspeptin and AMH have a unique significance in the auxiliary diagnosis, the differential diagnosis, the treatment, and prognosis of sexual puberty disorder.

The synthesis of anthocyanin in pear (Pyrus bretschneideri) fruit is regulated by light. However, little is known about the molecular mechanisms of pear fruit coloring mediated by upstream light-signaling regulators. Here, the photoresponse factors CONSTITUTIVE PHOTOMORPHOGENIC (COP) 1.1 and 1.2 were cloned from ‘Red Zaosu’ peel to study their functions in pear fruit coloring. The overexpression vectors pBI121-PbCOP1.1 and pBI121-PbCOP1.2 were constructed to analyze their effects on anthocyanin synthesis in pear fruit. A protein sequence alignment and phylogenetic tree analysis revealed that PbCOP1 proteins are highly homologous with those of other species. An analysis of tissue differential expression showed that the greatest expression levels of PbCOP1s occurred in the leaves. Their expression levels increased in the leaves during development, when the leaves changed from red to green. The overexpression of PbCOP1s in the peel resulted in reduced anthocyanin synthesis at the injection sites. A quantitative PCR analysis of the injection sites showed that PbCOP1.1 significantly inhibited the expression of the anthocyanin synthesis-related genes CHI, DFR, UFGT2, bHLH3, HY5 and GST. Based on the above results, we hypothesize that PbCOP1.1 is an anthocyanin synthetic inhibitory factor of pear coloration.

Monitoring the quality of marine water is crucial for ensuring the health and sustainability of marine ecosystems. The conventional monitoring approach involves manual sampling using a water sampler, followed by packaging the water samples in plastic bottles and transporting them to a terrestrial laboratory for analysis. However, this method is time consuming, labor intensive, and cannot provide real-time data for addressing unforeseen circumstances. In response to these challenges, an advanced shipborne integrated platform for water quality inspection (ASIPWQI) has been proposed and implemented. This system automates the collection of multi-layer seawater samples in the vertical profile, conducts online measurements of monitoring elements, and provides real-time measurement data. In multiple sea trials, ASIPWQI successfully conducted onsite collection and measurement of a significant number of samples, meeting the water quality monitoring requirements in China’s nearshore waters. Comparative analysis of the laboratory measurement results for nutrients, heavy metals, and total phosphorus and nitrogen in water samples collected using automatic and manual methods revealed no significant differences between the two sampling approaches and demonstrated strong correlation. Further analysis using practical relative error (PRE) statistical methods showed that the data rate of most monitoring elements with relative errors less than 10% was higher than 70%, with nitrite, silicate, and phosphate even exceeding 90%. This indicate that ASIPWQI has excellent stability and applicability, offering a viable alternative to traditional manual sampling and laboratory testing. This innovation makes water quality monitoring significantly more efficient. [ABSTRACT FROM AUTHOR]

Objective(s) The prognostic value of systemic cytokine profiles and inflammatory markers in colorectal cancer were explored by several studies. We want to know more about inflammatory biomarkers in colorectal adenoma and early cancer. Method The level of 38 inflammatory markers in the plasma of 112 adenoma patients, 72 Tis-T1 staging of colorectal carcinoma patients, 34 T2–T4 staging of colorectal carcinoma patients and 53 normal subjects were detected and compared. Result(s) Eight inflammatory biomarkers (Eotaxin, GCSF, IL-4, IL-5, IL-17E, MCP-1, TNF-α and VEGF-A) have higher plasma concentrations in colorectal adenoma and cancer patients compared with normal participants over 50 years old. Conclusion(s) Inflammatory markers may have the prognostic value for colorectal adenoma and early-stage carcinoma. [ABSTRACT FROM AUTHOR]

Research on the development of flexible silica aerogels (FSAs) has been ongoing due to their excellent thermal insulation, low density, and high elasticity. However, the physical properties of FSAs, such as density, thermal conductivity, mechanical strength, and surface wettability, are highly dependent on the preparation conditions. To achieve the desired properties of FSAs for various applications, it is necessary to develop a method to fine-tune their physical properties. In this paper, two modifiers of methyltrimethoxysilane (MTMS)/trimethylethoxysilane (TMES) were employed to fine-tune the bulk density of a series of flexible silica aerogels (FSAs), reflecting a series of FSAs with fine-tunable physical properties. First, the precursor was synthesized by a click reaction between vinyltrimethoxysilane (VTMS) and 2,2′ (ethylenedioxy) diethanethiol (EDDET). The VTMS, EDDET, and the as-prepared precursor were characterized by FT-IR and NMR spectroscopy. Subsequently, the precursor was converted into a series of FSAs (denoted by FSA, FSA-M, and FSA-T) through conventional sol-gel reactions with/without MTMS/TMES. Chemical structures of synthesized FSAs were confirmed by 13C and 29Si solid-state NMR spectroscopy. The porous structure of FSAs was identified by BET and SEM, respectively. Physical properties, such as thermal conductivity, mechanical strength, and surface wettability of FSAs were determined by a Hot Disk, durometer/DMA in compression mode, and contact angle measurements, respectively. This study found FSAs containing none, 1 wt%, 5 wt%, and 10 wt% of MTMS increase the density of FSAs from 0.419 g/cm3 (FSA), 0.423 g/cm3 (FSA-M1), 0.448 g/cm3 (FSA-M5), and 0.456 g/cm3 (FSA-M10). It should be noted that the thermal conductivity, surface hardness, bulk mechanical strength, and hydrophobicity of FSA-Ms of increasing MTMS loading were all found to show a rising trend, while FSA-Ts exhibited lower density. FSA-T10 exhibited lower thermal conductivity, surface hardness, and bulk mechanical strength as compared to FSA. However, it was found to show higher hydrophobicity as compared to that of FSA. [ABSTRACT FROM AUTHOR]

Aim: We compared endoscopic "calabash" ligation and resection (ECLR) and endoscopic submucosal excision (ESE) in treating endophytic gastric stromal tumors (GSTs) ≤15 mm in diameter originating from the muscularis propria. Methods: We performed a retrospective study and included patients who visited our hospital for removal of small endophytic GSTs (diameter ≤ 15 mm) confirmed by postoperative pathological reports between February 2019 and December 2020. Patients were assigned to the study (received ECLR) or control (accepted ESE) groups, and their medical records were reviewed. Age, sex, GST size, resection outcomes, procedure measurements, lengths of hospital stays, medical expenses, intraoperative and postoperative complications, and follow‐up outcomes were documented and compared between the two groups. Propensity score matching was used to avoid retrospective biases. Results: A total of 277 patients were included in the analysis, with 135 in the study group and 142 in the control group. After propensity score matching, 119 cases in each group were finally included in the study. Compared to the control group, the study group had significantly shorter procedure durations and lengths of hospital stays, as well as reduced medical expenses. Compared to the control group, the study group also had significantly lower incidence rates of intraoperative stomach perforation, postoperative intraperitoneal infection, and postoperative electrocoagulation syndrome, as well as a lower intensity of postoperative pain. There were no significant differences in the other measurements between the two groups. Conclusion: ECLR is an effective and safe procedure for treating patients with endophytic GSTs ≤15 mm in diameter originating from the muscularis propria. [ABSTRACT FROM AUTHOR]

ABSTRACT An investigation into retrovirus was conducted in six species of bats (Myotis aurascens, Myotis petax, Myotis macrodactylus, Miniopterus fuliginosus, Rhinolophus ferrumequinum, and Pipistrellus abramus) inhabiting South Korea. Exogenous retroviruses (XRVs) were detected in the tissue samples of R. ferrumequinum individuals by PCR assay. Proviruses were identified in all tissue samples through viral quantification using a digital PCR assay per organ (lung, intestine, heart, brain, wing, kidney, and liver), with viral loads varying greatly between each organ. In phylogenetic analysis based on the whole genome, the Korean bat retroviruses and the R. ferrumequinum retrovirus (RfRV) strain formed a new clade distinct from the Gammaretrovirus clade. The phylogenetic results determined these viruses to be RfRV-like viruses. In the Simplot comparison, Korean RfRV-like viruses exhibited relatively strong fluctuated patterns in the latter part of the envelope gene area compared to other gene areas. Several point mutations within this region (6,878–7,774 bp) of these viruses were observed compared to the RfRV sequence. One Korean RfRV-like virus (named Y4b strain) was successfully recovered in the Raw 264.7 cell line, and virus particles replicated in the cells were confirmed by transmission electron microscopy. RfRVs (or RfRV-like viruses) have been spreading since their first discovery in 2012, and the Korean RfRV-like viruses were assumed to be XRVs that evolved from RfRV.IMPORTANCER. ferrumequinum retrovirus (RfRV)-like viruses were identified in greater horseshoe bats in South Korea. These RfRV-like viruses were considered exogenous retroviruses (XRVs) that emerged from RfRV. Varying amounts of provirus detected in different organs suggest ongoing viral activity, replication, and de novo integration in certain organs. Additionally, the successful recovery of the virus in the Raw 264.7 cell line provides strong evidence supporting their status as XRVs. These viruses have now been identified in South Korea and, more recently, in Kenya since RfRV was discovered in China in 2012, indicating that RfRVs (or RfRV-like viruses) have spread worldwide.

The adoption of one-bit analog-to-digital converters (ADCs) in wireless communication has become increasingly popular, owing to their potential to reduce power consumption. However, there is a decreased spectral efficiency (SE) associated with their use, as they are unable to take advantage of high-modulation-order signaling. Faster-than-Nyquist (FTN) signaling along with oversampling are promising means of improving SE at the expense of additional inter-symbol interference (ISI). This study establishes a common platform for design and evaluation by providing a general system model and problem formulation, as well as proposing an alternative solution framework for the one-bit quantization system. By systematically evaluating optimizable factors that impact performance, such as signaling rate, transmit sequences, and error correction blocks, this study proposes a deep learning (DL)-based architecture, specifically channel autoencoders, for end-to-end communication over a one-bit quantization channel. Various transceiver designs are proposed for performance comparison as well as to enable one-bit quantized communication at previously unattainable information rates through conventional means. Numerical results showcase the superiority of jointly optimizing all blocks in an additive white Gaussian noise (AWGN) channel. The DL-based scheme operationalizes Bit Error Rate (BER) performance at information rates scaling up to 80% of Shamai’s limit. Beyond AWGN, the autoencoder-based transceiver design extends to make one-bit quantization viable over a challenging Rayleigh multipath fading channel. A detailed analysis compares a pilot-based scheme for one-bit quantization with a pilotless option, thereby revealing their SE and BER relationship. The pilot-based quantized scheme outperforms conventional fading channel transmission without quantization by up to 10 dB.

Finite element (FE) analysis of the tensile test of TWB-HPF 22MnB5 steel was performed and compared with the experimental results. To improve the accuracy of the simulation, the damage theory of FLD and ductile damage theory were used in 2D and 3D simulations. The tensile strength of 22MnB5 steel was determined under various welding heat inputs for FE simulation. Crack propagation of the welded region indicated that the fracture was observed in the base metal under normal welding conditions. Also, the crack propagated along the HAZ region due to higher heat input of the welding, and lead fractures have been highlighted as a potential complication.

Abstract Background Breast cancer is the global leading cancer burden in women and the hormone receptor-positive (HR+) subtype is a major part of breast cancer. Though cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors are highly effective therapy for HR+ subtype, acquired resistance is inevitable in most cases. Herein, we investigated the paternally expressed gene 10 (PEG10)-associated mechanism of acquired resistance to CDK4/6 inhibitors. Methods Palbociclib-resistant cells were generated by exposing human HR+ breast cancer cell lines to palbociclib for 7–9 months. In vitro mechanistic study and in vivo xenograft assay were performed. For clinical relevance, public mRNA microarray data sets of early breast cancer were analyzed and PEG10 immunohistochemical staining was performed using pre-CDK4/6 inhibitor tumor samples. Results We observed that PEG10 was significantly upregulated in palbociclib-resistant cells. Ectopic overexpression of PEG10 in parental cells caused CDK4/6 inhibitor resistance and enhanced epithelial–mesenchymal transition (EMT). On the contrary, PEG10-targeting siRNA or antisense oligonucleotides (ASOs) combined with palbociclib synergistically inhibited proliferation of palbociclib-resistant cells and growth of palbociclib-resistant xenograft in mice and suppressed EMT as well. The mechanistic study confirmed that high PEG10 expression suppressed p21, a natural CDK inhibitor, and SIAH1, a post-translational degrader of ZEB1, augmenting CDK4/6 inhibitor resistance. Then PEG10 siRNA combined with palbociclib suppressed cell cycle progression and EMT via activating p21 and SIAH1, respectively. Consequently, combined PEG10 inhibition and palbociclib overcame CDK4/6 inhibitor resistance. Furthermore, high PEG10 expression was significantly associated with a shorter recurrence-free survival (RFS) based on public mRNA expression data. In pre-CDK4/6 inhibitor treatment tissues, PEG10 positivity by IHC also showed a trend toward a shorter progression-free survival (PFS) with CDK4/6 inhibitor. These results support clinical relevance of PEG10 as a therapeutic target. Conclusions We demonstrated a novel PEG10-associated mechanism of CDK4/6 inhibitor resistance. We propose PEG10 as a promising therapeutic target for overcoming PEG10-associated resistance to CDK4/6 inhibitors.

We synthesized and investigated the boron-doped and boron/nitrogen co-doped large single-crystal diamonds grown under high pressure and high temperature (HPHT) conditions (5.9 GPa and 1290 °C). The optical and electrical properties and surface characterization of the synthetic diamonds were observed and studied. Incorporation of nitrogen significantly changed the growth trace on surface of boron-containing diamonds. X-ray photoelectron spectroscopy (XPS) measurements showed good evident that nitrogen atoms successfully incorporate into the boron-rich diamond lattice and bond with carbon atoms. Raman spectra showed differences on the as-grown surfaces and interior between boron-doped and boron/nitrogen co-doped diamonds. Fourier transform infrared spectroscopy (FTIR) measurements indicated that the nitrogen incorporation significantly decreases the boron acceptor concentration in diamonds. Hall measurements at room temperature showed that the carriers concentration of the co-doped diamonds decreases, and the mobility increases obviously. The highest hole mobility of sample BNDD-1 reached 980 cm2⋅V−1⋅s−1, possible reasons were discussed in the paper. [ABSTRACT FROM AUTHOR]

This study explores the development status and dissemination effect of Jidong folk songs under the perspective of intangible cultural heritage through VAR modeling, to provide new perspectives and methods for protecting and inheriting traditional folk songs. Using a panel space VAR model, the effects of intangible cultural heritage protection, human capital and physical capital on Jidong folk songs were analyzed. The study first utilizes the VAR model for lag determination and smoothness test, then explores the variables’ interactions through the impulse response analysis path. The results show that human capital and physical capital of intangible cultural heritage protection have a significant positive effect on Jidong folk songs. In the analysis of the spread of Jidong folk songs, multiple linear regression analysis was used, and it was found that familiarity with Jidong folk songs, music appreciation preference and enjoyment after appreciation were the key factors affecting their spread. Protecting intangible cultural heritage promotes the development and dissemination of Jidong folk songs to a certain extent, but some negative impacts require further research and strategy optimization.

Background: A low appropriate therapy rate indicates that a minority of patients will benefit from their implantable cardioverter defibrillator (ICD). Quantitative measurements from 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) may predict ventricular arrhythmia (VA) occurrence after ICD placement.Methods: We performed a prospective observational study and recruited patients who required ICD placement. Pre-procedure image scans were performed. Patients were followed up for VA occurrence. Associations between image results and VA were analyzed.Results: In 51 patients (33 males, 53.9 ± 17.2 years) analyzed, 17 (33.3%) developed VA. Compared with patients without VA, patients with VA had significantly larger values in scar area (17.7 ± 12.4% vs. 7.0 ± 7.9%), phase standard deviation (51.4° ± 14.0° vs. 34.0° ± 15.0°), bandwidth (172.9° ± 39.8° vs. 128.7° ± 49.9°), sum thickening score (STS, 29.5 ± 11.1 vs. 17.8 ± 13.2), and sum motion score (42.9 ± 11.5 vs. 33.0 ± 19.0). Cox regression analysis and receiver operating characteristic curve analysis showed that scar size, dyssynchrony, and STS were associated with VA occurrence (HR, 4.956, 95% CI 1.70-14.46).Conclusion: Larger left ventricular scar burden, increased dyssynchrony, and higher STS quantified by 18F-FDG PET may indicate a higher VA incidence after ICD placement. [ABSTRACT FROM AUTHOR]

This paper proposes a novel method to impart intelligence to metal parts using additive manufacturing. A sensor-embedded metal bracket is prototyped via a metal powder bed fusion process to recognise partial screw loosening or total screw missing or identify the source of vibration with the assistance of artificial intelligence (AI). The digital metal bracket can recognise subtle changes in the screw fixation state with 90% accuracy and identify unknown sources of vibration with 84% accuracy. The von Mises stress distribution in the prototyped metal bracket is evaluated using a finite element analysis, which is learned by AI to match the real-time deformation analysis of the metal bracket in augmented reality. The proposed prototype can contribute to hyper-connectivity for developing next-generation metal-based mechanical components.

Introduction: Myosin IXB (MYO9B) is an unconventional myosin with RhoGAP activity and thus is a regulator of actin cytoskeletal organization. MYO9B was previously shown to be necessary for skeletal growth and health and to play a role in actin-based functions of both osteoblasts and osteoclasts. However, its role in responses to mechanical stimulation of bone cells has not yet been described. Therefore, experiments were undertaken to determine the role of MYO9B in bone cell responses to mechanical stress both in vitro and in vivo.Methods: MYO9B expression was knocked down in osteoblast and osteocyte cell lines using RNA interference and the resulting cells were subjected to mechanical stresses including cyclic tensile strain, fluid shear stress, and plating on different substrates (no substrate vs. monomeric or polymerized collagen type I). Osteocytic cells were also subjected to MYO9B regulation through Slit-Robo signaling. Further, wild-type or Myo9b−/− mice were subjected to a regimen of whole-body vibration (WBV) and changes in bone quality were assessed by micro-CT.Results: Unlike control cells, MYO9B-deficient osteoblastic cells subjected to uniaxial cyclic tensile strain were unable to orient their actin stress fibers perpendicular to the strain. Osteocytic cells in which MYO9B was knocked down exhibited elongated dendrites but were unable to respond normally to treatments that increase dendrite length such as fluid shear stress and Slit-Robo signaling. Osteocytic responses to mechanical stimuli were also found to be dependent on the polymerization state of collagen type I substrates. Wild-type mice responded to WBV with increased bone tissue mineral density values while Myo9b−/− mice responded with bone loss.Discussion: These results demonstrate that MYO9B plays a key role in mechanical stress-induced responses of bone cells in vitro and in vivo.

Poly (ADP-ribose) polymerase (PARP) inhibitors are effective against BRCA1/2-mutated cancers through synthetic lethality. Unfortunately, most cases ultimately develop acquired resistance. Therefore, enhancing PARP inhibitor sensitivity and preventing resistance in those cells are an unmet clinical need. Here, we investigated the ability of paraspeckle component 1 (PSPC1), as an additional synthetic lethal partner with BRCA1/2, to enhance olaparib sensitivity in preclinical models of BRCA1/2-mutated breast and ovarian cancers. In vitro, the combined olaparib and PSPC1 small interfering RNA (siRNA) exhibited synergistic anti-proliferative activity in BRCA1/2-mutated breast and ovarian cancer cells. The combination therapy also demonstrated synergistic tumor inhibition in a xenograft mouse model. Mechanistically, olaparib monotherapy increased the expressions of p-ATM and DNA-PKcs, suggesting the activation of a DNA repair pathway, whereas combining PSPC1 siRNA with olaparib decreased the expressions of p-ATM and DNA-PKcs again. As such, the combination increased the formation of γH2AX foci, indicating stronger DNA double-strand breaks. Subsequently, these DNA-damaged cells escaped G2/M checkpoint activation, as indicated by the suppression of p-cdc25C (Ser216) and p-cdc2 (Tyr15) after combination treatment. Finally, these cells entered mitosis, which induced increased apoptosis. Thus, this proves that PSPC1 inhibition enhances olaparib sensitivity by targeting DNA damage response in our preclinical model. The combination of olaparib and PSPC1 inhibition merits further clinical investigation to enhance PARP inhibitor efficacy.

[Objectives] To explore the protective effect of Sanguis Draconis flavones (SDF) on rat focal cerebral ischemia-reperfusion injury (CIRI) models established by middle cerebral artery occlusion (MCAO). [Methods] A total of 60 healthy adult male Sprague-Dawley rats were selected. They were evenly and randomly divided into sham group, model group, edaravone group (12 mg/kg) and SDF group (360 mg/kg), and administered intragastrically and intraperitoneally. The middle cerebral artery of each rat was blocked by suture-occluded method to establish a CIRI model. After ischemia for 2 h and reperfusion for 48 h, the pathological injury on the ischemic side was observed by HE staining; the neuron and myelin sheath structure was observed by transmission electron microscopy; the expression of G protein-coupled receptor kinase 2 (GRK2) was preserved by immunohistochemistry; and the transfer of GRK2 was detected by western-blot. [Results] After 48 h of CIRI, the nuclei of the penumbral cortical neurons shrank, the chromatin was unevenly distributed, the nuclear membrane was dis-solved and the mitochondria in the cytoplasm were swollen and vacuolated. The myelin layer was disordered. With this change, the distribution of GRK2 subcellular cells in the penumbra of the injured lateral cortex transferred from the cytoplasm to the membrane. SDF can effectively restore neuronal and myelin sheath structural damage and reduce the functional (membrane coupling) expression of GRK2. [Conclusions] GRK2 may be an effective target for SDF to protect the impaired blood-brain barrier (BBB) in CIRI. [ABSTRACT FROM AUTHOR]

Using a tailor-welded blank (TWB) and hot-press forming (HPF), a 22MnB5 blank was surface-treated under four conditions. The penetration rates of the FexAly compounds under the four surface-treatment conditions were investigated, and the hardness values were measured. A finite element (FE) simulation was performed for the characteristics of the heat-affected zone (HAZ), using the hardness value and results of previous researchers. In particular, the mechanical property settings of the mesh were designed to realize the conditions for the FexAly compounds in the HAZ. Fine meshing was performed by partitioning the HAZ sections. For the mechanical properties of the HAZ with the FexAly compounds, the strength was predicted from the hardness value, and the elongation values investigated by other researchers were used. The forming limit diagram, which was proportional to the elongation, was predicted. Specific elements were defined as the areas with FexAly compounds, which played the same role as impurities. Tensile TWB–HPF specimens with different HAZ characteristics under four surface-treatment conditions were fabricated. Experiments and FE simulations were performed and compared. Details are as follows: For loads, a minimum error rate of 3% and a maximum error rate of 6% were obtained. For displacement, a minimum error rate of 9% and a maximum error of 25% were obtained. The feasibility of the simulation was verified by comparing the simulation and experimental results. A match of more than 75% was obtained.

A processing map is required for Ti alloys to find processing parameters securing a high formability. This study adopted the extreme gradient boosting (XGB) approach of machine learning to predict a flow curve and plot a processing map with less experiments for the first time. The optimum XGB model predicted flow curves of Ti–6Al–2Sn–2Zr–2Mo–2Cr–0.15Si at 1073–1273 K and 10 s−1. The predicted data were used to plot a processing map, which showed a higher accuracy in the instability map as compared with the map without XGB. The XGB model also anticipated the power dissipation map at low strain rates. The low accuracy at high strain rates would be improved by alleviating the bias towards a flow hardening. This work has successfully proven the potential usefulness of XGB for plotting an enhanced processing map in light of a higher accuracy with less experiments.

Background: Irritable bowel syndrome (IBS) is a functional disorder characterized by abdominal pain and abnormalities in defecation associated with psychiatric disorders such as depression and anxiety due to the dysfunction of brain-gut axis. This study aims to determine whether trans-Resveratrol affects chronic-acute combined stress (CACS)-induced IBS-like symptoms including depression, anxiety and intestinal dysfunction. Methods: ICR male mice were exposed to the CACS for 3 weeks. trans-Resveratrol were administrated daily (2.5, 5, and 10 mg/kg, i.g.) 30min before CACS. Behavioral tests were performed to evaluate the treatment effects of trans-Resveratrol on IBS. Hippocampus tissues were collected and processed Golgi staining and immuno-blot analysis. Ileum and colon tissues were collected and processed Hematoxylin and Eosin staining and immuno-blot analysis. Results: Administration with trans-Resveratrol before CACS for 3 weeks significantly reversed CACS-induced depression- and anxiety-like behaviors and intestinal dysfunction in mice, which implied a crucial role of trans-Resveratrol in treatment of IBS-like disorder. Furthermore, trans-Resveratrol improved hippocampal neuronal remodeling, protected ileal and colonic epithelial barrier structure against CACS insults. The further study suggested that trans-Resveratrol normalized phosphodiesterases 4A (PDE4A) expression and CREB-BDNF signaling that were disturbed by CACS. The increased pCREB and BDNF expression in the hippocampus were found, while decreased pCREB and BDNF levels were observed after treatment with trans-Resveratrol. Conclusions: The dual effects of trans-Resveratrol on stress-induced psychiatric and intestinal dysfunction may be related to normalization of PDE4A expression and subsequent pCREB-BDNF signaling in the hippocampus, ileum and colon. [ABSTRACT FROM AUTHOR]

Abstract Objective To identify patients with Mycoplasma pneumoniae pneumonia (MPP) with a risk of prolonged fever while on macrolides. Methods A retrospective study was performed with 716 children admitted for MPP. Refractory MPP (RMPP-3) was defined as fever persisting for > 72 h without improvement in clinical and radiologic findings after macrolide antibiotics (RMPP-3) or when fever persisted for > 120 h (RMPP-5) without improvement in clinical and radiologic findings. Radiological data, laboratory data, and fever profiles were compared between the RMPP and non-RMPP groups. Fever profiles included the highest temperature, lowest temperature, and frequency of fever. Prediction models for RMPP were created using the logistic regression method and deep neural network. Their predictive values were compared using receiver operating characteristic curves. Results Overall, 716 patients were randomly divided into two groups: training and test cohorts for both RMPP-3 and RMPP-5. For the prediction of RMPP-3, a conventional logistic model with radiologic grouping showed increased sensitivity (63.3%) than the model using laboratory values. Adding laboratory values in the prediction model using radiologic grouping did not contribute to a meaningful increase in sensitivity (64.6%). For the prediction of RMPP-5, laboratory values or radiologic grouping showed lower sensitivities ranging from 12.9 to 16.1%. However, prediction models using predefined fever profiles showed significantly increased sensitivity for predicting RMPP-5, and neural network models using 12 sequential fever data showed a greatly increased sensitivity (64.5%). Conclusion RMPP-5 could not be effectively predicted using initial laboratory and radiologic data, which were previously reported to be predictive. Further studies using advanced mathematical models, based on large-sized easily accessible clinical data, are anticipated for predicting RMPP.

The results of the 4th National Ecological Survey reflect the latest status of the ecological environment in South Korea. In this study, we presented spatial data on the distribution of mammals collected through the 4th National Ecological Survey in the southwestern area of the Korean Peninsula, covering Jeollanam-do, Gwangju Metropolitan City and Jeju island. The data consists of information on mammal individuals recorded at the site and information on characteristics of abiotic environment at the recorded points, including spatial units (administrative districts, digital map index, etc.) which are necessary for statistical analysis. The data have high policy and research values because it can elaborate on the descriptive characteristics of the distribution points and identify the relationship between individual abundance and habitat environment. However, when data is utilized in a regional scale, it should precede to consider the survey system, such as how to select the survey area.