Search

Geminal bromofluoroalkenes are an important subclass of versatile organic interhalide, which can serve as useful synthetic precursors to monofluoroalkenes that are valuable amide group isosteres. Nonetheless, despite the vast advancement of olefination methodologies, the broadly applicable stereoselective synthesis remained elusive for geminal bromofluoroalkenes before our work. In particular, the seemingly straightforward Wittig-type approach with interhalogenated phosphorus ylide has been unsuccessful because of the difficulty in the diastereoselective oxaphosphetane formation. Here, we describe a conceptually distinctive strategy, by which the stereoselectivity is gained via the selective decomposition of the oxaphosphetane intermediates. The suitably identified phosphorus(III) reagent and reaction medium enabled efficient kinetic differentiation, which was supported by nuclear magnetic resonance analysis and density functional theory calculation. Through our method, the highly diastereoselective synthesis of geminal E -bromofluoroalkenes was accomplished in one step. Furthermore, the generality was demonstrated by accommodating a wide range of readily available carbonyl compounds, including ketones and pharmaceutical substrates.

Acute lung injury (ALI) is the pathophysiological precursor of acute respiratory distress syndrome. It is characterized by increased oxidative stress and exaggerated inflammatory response that disrupts redox reactions and immune homeostasis in the lungs, thereby posing significant clinical challenges. In this study, an internally functionalized thioether-enriched dendrimer Sr-G4-PEG is developed, to scavenge both proinflammatory cytokines and reactive oxygen species (ROS) and restore homeostasis during ALI treatment. The dendrimers are synthesized using an efficient and orthogonal thiol-ene "click" chemistry approach that involves incorporating thioether moieties within the dendritic architectures to neutralize the ROS. The ROS scavenging of Sr-G4-PEG manifests in its capacity to sequester proinflammatory cytokines. The synergistic effects of scavenging ROS and sequestering inflammatory cytokines by Sr-G4-PEG contribute to redox remodeling and immune homeostasis, along with the modulation of the NLRP3-pyroptosis pathway. Treatment with Sr-G4-PEG enhances the therapeutic efficacy of ALIs by alleviating alveolar bleeding, reducing inflammatory cell infiltration, and suppressing the release of inflammatory cytokines. These results suggest that Sr-G4-PEG is a potent nanotechnological candidate for remodeling redox and immune homeostasis in the treatment of ALIs, demonstrating the great potential of dendrimer-based nanomedicine for the treatment of respiratory pathologies., (© 2024 Wiley‐VCH GmbH.)

Depression and metabolic syndrome could exacerbate the risks of the other, leading to a series of severe coexisting conditions. One notable comorbidity that must be mentioned is obstructive sleep apnea (OSA). Current studies suggested that depression increases susceptibility to OSA. As the prevalence of depression rises, it becomes critical to prevent and manage its complications or comorbidities, including OSA. Predictive models, non-invasive electroencephalogram monitoring, genetic research, and other promising technologies are being applied to the prevention, diagnosis, and personalized treatment of depression and OSA., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Medication-Related Osteonecrosis of the Jaw (MRONJ) is characterized by bone exposure in the oral and maxillofacial region for more than eight weeks in patients treated with anti-resorptive agents, immunosuppressants, or anti-angiogenic agents, without prior radiation therapy or metastatic disease to the jaws. Conservative treatments can control infection in mild cases, but surgical intervention is necessary for patients with severe symptoms. A 78-year-old female with a history of bisphosphonate treatment for osteoporosis presented with persistent pain, swelling, and malodor following implant placement in the upper right maxilla. SPECT/CT imaging revealed a high-risk hot spot in the right maxillary region. BIS-guided surgery using the Qray pen-C was performed, selectively removing red fluorescent bone tissue. The defect was grafted with HuBT incorporated with rhBMP-2. Postoperative follow-ups at 4, 7, and 14 months showed successful bone healing, transforming into a corticocancellous complex, and implant placement without MRONJ recurrence. Allogeneic demineralized dentin matrix (DDM) incorporated with rhBMP-2 demonstrates effective bone healing and implant placement following BIS-guided MRONJ surgery. This case supports the use of DDM/rhBMP-2 for tissue regeneration in MRONJ treatment, enabling successful prosthetic restoration without recurrence.

The Moving Protecting-Qi ( Wei Qi Xing ), in Lingshu , one of the volumes of the Inner Cannon of Huangdi , records two types of circulatory routes which were believed to link man and nature (a traditional Chinese medicine theory that argues man is an integral part of nature). The first type of circulatory route matched the Sun and twenty-eight lunar mansions because it was believed that the Protecting-Qi circulates through different body parts of human during the day and night. This indicates that the Protecting-Qi passes through the meridians at day time and washes the five viscera at night. The second type matched the hourglass. This means it does twenty-five cycles circulation through three Yang and one Yin in the human body on a centigrade scale. The Protecting-Qi in Lingshu attempted to unify the two circulatory routes numerically by equating the two different time measures-the sun moving and the hourglass. Additionally, it implicitly took an ambiguous concept of 'Yin Fen' to replace the different parts of the five viscera, attempting to unify the two circulatory routes together. However, because of the intrinsic differences between the two circulatory routes, this effort does not make sense. It was found that the first circulatory route is mostly used in clinical practice to explain and treat disorders associated with yawning and insomnia, yet there exists a subtle difference in theoretical explanation.

Depression is a common occurrence among cancer patients, and it significantly impacts their clinical outcomes and quality of life, with a high incidence during anti-tumor treatment or after surgery. The association between surgery and depression is the result of the interaction of various factors, including physiological, psychological, and social factors, all of which are intertwined and make patients susceptible to depression after surgical treatment. Postoperative depression has a significant negative impact on many aspects of cancer patients, and it requires timely identification and intervention to improve the overall outcome., Competing Interests: Conflict-of-interest statement: The authors declare no conflict of interests., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Introduction: To evaluate the diagnostic efficiency among the clinical model, the radiomics model and the nomogram that combined radiomics features, frozen section (FS) analysis and clinical characteristics for the prediction of lymph node (LN) metastasis in patients with papillary thyroid cancer (PTC)., Methods: A total of 208 patients were randomly divided into two groups randomly with a proportion of 7:3 for the training groups (n = 146) and the validation groups (n = 62). The Least Absolute Shrinkage and Selection Operator (LASSO) regression was used for the selection of radiomics features extracted from ultrasound (US) images. Univariate and multivariate logistic analyses were used to select predictors associated with the status of LN. The clinical model, radiomics model and nomogram were subsequently established by logistic regression machine learning. The area under the curve (AUC), sensitivity and specificity were used to evaluate the diagnostic performance of the different models. The Delong test was used to compare the AUC of the three models., Results: Multivariate analysis indicated that age, size group, Adler grade, ACR score and the psammoma body group were independent predictors of lymph node metastasis (LNM). The results showed that in both the training and validation groups, the nomogram showed better performance than the clinical model, albeit not statistically significant (p > .05), and significantly outperformed the radiomics model (p < .05). However, the nomogram exhibits a slight improvement in sensitivity that could reduce the incidence of false negatives., Conclusion: We propose that the nomogram holds substantial promise as an effective tool for predicting LNM in patients with PTC., (© 2024 John Wiley & Sons Ltd.)

In this paper, we consider the problem of asynchronous estimation in the presence of packet losses for the randomly sampling nonlinear system. Packet losses occur at the control input and at the measurement side. Firstly, the synchronization of the asynchronous sampling system is realized by weighting the state of the adjacent state update points. Secondly, the projection theorem is used to estimate the system state at the sampling time. Due to modeling errors and unmodeled dynamics, obtaining an accurate dynamic model is challenging. Therefore, observation inference based on interpolation techniques is proposed to solve the asynchronous estimation problem. Furthermore, the algorithm is extended to multi-sensor systems to obtain a distributed fusion estimator. Finally, simulation experiments are conducted to validate the effectiveness of the algorithm.

Purpose: Asthma can not be eradicated till now and its control primarily relies on the application of corticosteroids. Recently, glycolytic reprogramming has been reportedly contributed to asthma, this study aimed to reveal whether the effect of corticosteroids on asthma control is related to their regulation of glycolysis and glycolysis-dependent protein lactylation., Methods: Ovalbumin (OVA) aeroallergen was used to challenge mice and stimulate human macrophage cell line THP-1 following dexamethasone (DEX) treatment. Airway hyperresponsiveness, airway inflammation, the expressions of key glycolytic enzymes and pyroptosis markers, the level of lactic acid, real-time glycolysis and oxidative phosphorylation (OXPHOS), and protein lactylation were analyzed., Results: DEX significantly attenuated OVA-induced eosinophilic airway inflammation, including airway hyperresponsiveness, leukocyte infiltration, goblet cell hyperplasia, Th2 cytokines production and pyroptosis markers expression. Meanwhile, OVA-induced Hif-1α-glycolysis axis was substantially downregulated by DEX, which resulted in low level of lactic acid. Besides, key glycolytic enzymes in the lungs of asthmatic mice were notably co-localized with F4/80-positive macrophages, indicating metabolic shift to glycolysis in lung macrophages during asthma. This was confirmed in OVA-stimulated THP-1 cells that DEX treatment resulted in reductions in pyroptosis, glycolysis and lactic acid level. Finally, protein lactylation was found significantly increased in the lungs of asthmatic mice and OVA-stimulated THP-1 cells, which were both inhibited by DEX., Conclusion: Our present study revealed that the effect of DEX on asthma control was associated with its suppressing of Hif-1α-glycolysis-lactateaxis and subsequent protein lactylation, which may open new avenues for the therapy of eosinophilic asthma., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Asthma demonstrates a strong circadian rhythm with disrupted molecular clock. Melatonin which can directly regulate circadian rhythm has been reported to alleviate asthma, but whether this effect is related to its regulation on circadian clock has not yet been known. Here, female C57BL/6 mice were challenged with ovalbumin (OVA) to establish allergic airway inflammation, and were treated with melatonin or Luzindole to investigate whether the expressions of circadian clock proteins were changed in response to OVA and were affected by exogenous/endogenous melatonin. Airway inflammation, mucus secretion, protein expressions of circadian proteins (Bmal1, Per1, Clock, Timeless, Cry1 and Cry2), melatonin biosynthetase (ASMT, AANAT) and melatonin receptor (Mel-1A/B-R) were analyzed accordingly. The results showed that in the successfully established allergic airway inflammation model, inflammatory cells infiltration, expressions of circadian clock proteins in the lung tissues of OVA-challenged mice were all notably up-regulated as compared to that of the vehicle mice. Meanwhile, the protein expression of ASMT and the level of melatonin in the lung tissues were reduced in allergic mice, while the expression of melatonin receptor Mel-1A/B-R was markedly increased. After addition of exogenous melatonin, the OVA-induced airway inflammation was pronouncedly ameliorated, while simultaneously the OVA-induced expressions of Per1 and Clock were further increased. However, a melatonin receptor antagonist Luzindole further augmented the OVA-induced airway inflammation, accompanied with remarkably decreased expressions of Per1, Bmal1, Cry1 and Cry2 but notably increased expression of Timeless. Collectively, our results demonstrated that the expression of circadian clock proteins was increased in the lungs during allergic airway inflammation, and Per1 was a clock protein that can be regulated by both exogenous and endogenous melatonin, suggesting Per1 may be an important potential circadian clock target for melatonin as a negative regulatory factor against Th2-type airway inflammation., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Understanding the clinical course and pivotal time points of COVID-19 aggravation is critical for enhancing patient monitoring. This retrospective, multi-center cohort study aims to identify these significant time points and associate them with potential risk factors, leveraging data from a sizable cohort with mild-to-moderate symptoms upon admission., Methods: This study included data from 1,696 COVID-19 patients with mild-to-moderate clinical severity upon admission across multiple hospitals in Daegu-Kyungpook Province (Daegu dataset) between February 18 and early March 2020 and 321 COVID-19 patients at Seoul Boramae Hospital (Boramae dataset) collected from February to July 2020. The approach involved: (1) identifying the optimal time point for aggravation using survival analyses with maximally selected rank statistics; (2) investigating the relationship between comorbidities and time to aggravation; and (3) developing prediction models through machine learning techniques. The models were validated internally among patients from the Daegu dataset and externally among patients from the Boramae dataset., Results: The Daegu dataset showed a mean age of 51.0 ± 19.6 years, with 8 days for aggravation and day 5 being identified as the pivotal point for survival. Contrary to previous findings, specific comorbidities had no notable impact on aggravation patterns. Prediction models utilizing factors including age and chest X-ray infiltration demonstrated promising performance, with the top model achieving an AUC of 0.827 in external validation for 5 days aggravation prediction., Conclusion: Our study highlights the crucial significance of the initial 5 days period post-admission in managing COVID-19 patients. The identification of this pivotal time frame, combined with our robust predictive models, provides valuable insights for early intervention strategies. This research underscores the potential of proactive monitoring and timely interventions in enhancing patient outcomes, particularly for those at risk of rapid aggravation. Our findings offer a meaningful contribution to understanding the COVID-19 clinical course and supporting healthcare providers in optimizing patient care and resource allocation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Moon, Ham, Song, Lee, Goo, Oh, Lee, Kim and Park.)

In this work, a series of 2-(trifluoromethyl)quinolin-4-amine derivatives were designed and synthesized through structural optimization strategy as a microtubule-targeted agents (MTAs) and their cytotoxicity activity against PC3, K562 and HeLa cell lines were evaluated. The half maximal inhibitory concentration (IC 50 ) of 5e, 5f, and 5o suggested that their potency of anti-proliferative activities against HeLa cell lines were better than the combretastatin A-4. Compound 5e showed the higher anti-proliferative activity against PC3, K562 and HeLa in vitro with IC 50 values of 0.49 µM, 0.08 µM and 0.01 µM, respectively. Further mechanism study indicated that the representative compound 5e was new class of tubulin inhibitors by EBI competition assay and tubulin polymerization assays, it is similar to colchicine. Immunofluorescence staining revealed that compound 5e apparently disrupted tubulin network in HeLa cells, and compound 5e arrested HeLa cells at the G2/M phase and induced cells apoptosis in a dose-dependent manner. Molecular docking results illustrated that the hydrogen bonds of represented compounds reinforced the interactions in the pocket of colchicine binding site. Preliminary results suggested that 5e deserves further research as a promising tubulin inhibitor for the development of anticancer agents., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The nephrotoxicity of bortezomib, a proteasome inhibitor, has not yet been elucidated, although tumor lysis syndrome (TLS) associated with multiple myeloma (MM) has been reported to increase after introduction of the drug. This study compared the incidence and risk factors for acute kidney injury (AKI) and TLS in patients with MM after bortezomib-based chemotherapy to investigate drug-related nephrotoxicity., Methods: From 2006 to 2017, 276 patients who underwent a first cycle of bortezomib-based chemotherapy for MM were identified in a single tertiary hospital. Laboratory TLS was defined according to the Cairo-Bishop definition. Development of AKI was assessed by AKI Network criteria within 7 days of the first chemotherapy., Results: The median (interquartile range) age was 65 (56-72) years, and baseline estimated glomerular filtration rate (eGFR) was 61.3 (34.1-89.1) mL/min/1.73 m2. The incidences of AKI and laboratory TLS were 17% (n = 47) and 13% (n = 36), respectively. Ten (3.6%) subjects met both AKI and TLS criteria. Multivariate analyses showed that lower eGFR category [30-59, odds ratio (OR) 3.005 (95% confidence interval 1.163-7.976); 15-29, OR 4.225 (1.183-15.000); <15, OR 16.154 (3.831-70.920) vs ≥60, P < .001], lower serum albumin level [per 1 increase, OR 0.479 (0.256-0.871), P = .018], renal amyloidosis [OR 13.039 (4.108-44.041), P < .001] and use of acyclovir during bortezomib treatment [OR 3.689 (1.133-14.469), P = .042] were predictors of AKI. MM stages and β-2-microglobulin were not associated with increased risk of AKI. Regarding laboratory TLS, MM stage and β-2-microglobulin were higher in those with TLS than in others. In multivariate analyses, β-2-microglobulin level [OR 1.204 (1.005-1.461), P = .038] and absence of high-risk chromosome abnormalities [OR 0.143 (0.022-0.588), P = .016] were associated with higher risk of TLS., Conclusions: Development of AKI was often observed in the absence of TLS in patients with MM after treatment with bortezomib. In addition, the risk factors for AKI and TLS varied widely. These findings indicate the potential nephrotoxicity of bortezomib irrespective of TLS in patients with decreased kidney function., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

Background: The sagittal plane of spine-pelvis morphology of adult patients with lumbar disc herniation (LDH) differs from that of normal people. There is a correlation between abnormal sagittal plane morphology and adult LDH. This study aimed to investigate the relationship between LDH in young people and the Roussouly classification in the sagittal alignment of the spine and pelvis., Methods: A total of 126 patients with LDH hospitalized in our tertiary hospital between January 2020 and January 2021 who met the inclusion and exclusion criteria were retrospectively analyzed in a cross-sectional study. Participants were grouped according to the spinal level of disc herniation (L4/5 group, L5/S1 group, L3/4 group). Pelvic incidence (PI), pelvic tilt (PT), and sacral slope (SS) of all cases were measured using standing lateral spinal radiographs. Facet joint angles (FJA) were measured using lumbar computed tomography (CT) horizontal radiographs, and the height of the anterior, middle, and posterior margins of the herniated disc was measured using sagittal radiographs. The classification of Pfirrmann disc degeneration was determined via magnetic resonance imaging (MRI) film of the lumbar region. Roussouly classification was performed according to sagittal plane morphology, and data were analyzed among each group., Results: In all, 126 patients aged from 18 to 40 years, with an average age of 31.04±5.886 years were included. There were 63 cases of L4/5 disc herniation, 59 cases of L5/S1 herniation, and 4 cases of L3/4 herniation. There were 35 cases of epiphyseal separation. The Roussouly classification included 21 cases of type 1, 56 cases of type 2, 32 cases of type 3, 4 cases of type 4, and 13 cases of type 3 + anteverted pelvis (type 3-AP). The L4/5 disc herniation group had significantly more types 2 and 3 than the other groups, and the L5/S1 disc herniation group had significantly more types 1 and 2 than the other groups. There were no significant differences in the Pfirrmann grade of intervertebral disc degeneration; epiphyseal separation; the height of anterior, middle, and posterior margins of the herniated disc; the difference between left and right facet angle and bilateral facet angle; and the thoracic kyphosis (TK) value among any of the groups (P>0.05). There were significant differences in PI, PT, SS, lumbar lordosis (LL), and height of the anterior and posterior margins of the intervertebral space among all groups (P<0.05). PI values were grouped at 50°; PT, SS, and LL were significantly different (P<0.05), whereas TK values were not significantly different between the 2 groups (P>0.05). SS values were grouped at 35°, and there were significant differences in PI, TK, and LL between the 2 groups (P<0.05). According to the disc herniation segment, the patients were divided into L4/5 and L5/S1 groups. There were significant differences in PI, PT, anterior edge height, anterior to posterior edge height, left facet angle, right facet angle, and bilateral facet angle (P<0.05)., Conclusions: LDH is common in L4/5 and L5/S1 segments. The incidence of Roussouly type 1 and 2 LDH is significantly higher than other types, and type 4 is the lowest. Small PI and small SS are more obvious in the L5/S1 segment. L5/S1 disc herniation is more common in patients with Roussouly type 1 and 2 classifications, whereas L4/5 disc herniation is more frequent in patients with Roussouly type 2 and 3 classifications., Competing Interests: Conflicts of Interest: All authors completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-22-503/coif). The authors have no conflicts of interest to declare., (2023 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Background: In randomized studies, the strategy of pulmonary vein antral isolation (PVI) plus linear ablation has failed to increase success rates for persistent atrial fibrillation (PeAF) ablation when compared with PVI alone. Peri-mitral reentry related atrial tachycardia due to incomplete linear block is an important cause of clinical failures of a first ablation procedure. Ethanol infusion (EI) into the vein of Marshall (EI-VOM) has been demonstrated to facilitate a durable mitral isthmus linear lesion., Objective: This trial is designed to compare arrhythmia-free survival between PVI and an ablation strategy termed upgraded '2C3L' for the ablation of PeAF., Study Design: The PROMPT-AF study (clinicaltrials.gov 04497376) is a prospective, multicenter, open-label, randomized trial using a 1:1 parallel-control approach. Patients (n = 498) undergoing their first catheter ablation of PeAF will be randomized to either the upgraded '2C3L' arm or PVI arm in a 1:1 fashion. The upgraded '2C3L' technique is a fixed ablation approach consisting of EI-VOM, bilateral circumferential PVI, and 3 linear ablation lesion sets across the mitral isthmus, left atrial roof, and cavotricuspid isthmus. The follow-up duration is 12 months. The primary end point is freedom from atrial arrhythmias of >30 seconds, without antiarrhythmic drugs, in 12 months after the index ablation procedure (excluding a blanking period of 3 months)., Conclusions: The PROMPT-AF study will evaluate the efficacy of the fixed '2C3L' approach in conjunction with EI-VOM, compared with PVI alone, in patients with PeAF undergoing de novo ablation., Competing Interests: Conflict of interest None reported., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Porcine reproductive and respiratory syndrome (PRRS) is an endemic disease in the Republic of Korea. Surveillance of PRRS virus (PRRSV) types is critical to tailor control measures. This study collected 5062 serum and tissue samples between 2018 and 2022. Open reading frame 5 (ORF5) sequences suggest that subgroup A (42%) was predominant, followed by lineage 1 (21%), lineage 5 (14%), lineage Korea C (LKC) (9%), lineage Korea B (LKB) (6%), and subtype 1C (5%). Highly virulent lineages 1 (NADC30/34/MN184) and 8 were also detected. These viruses typically mutate or recombine with other viruses. ORF5 and non-structural protein 2 (NSP2) deletion patterns were less variable in the PRRSV-1. Several strains belonging to PRRSV-2 showed differences in NSP2 deletion and ORF5 sequences. Similar vaccine-like isolates to the PRRSV-1 subtype 1C and PRRSV-2 lineage 5 were also found. The virus is evolving independently in the field and has eluded vaccine protection. The current vaccine that is used in Korea offers only modest or limited heterologous protection. Ongoing surveillance to identify the current virus strain in circulation is necessary to design a vaccine. A systemic immunization program with region-specific vaccinations and stringent biosecurity measures is required to reduce PRRSV infections in the Republic of Korea.

Endolysosomal defects in neurons are central to the pathogenesis of prion and other neurodegenerative disorders. In prion disease, prion oligomers traffic through the multivesicular body (MVB) and are routed for degradation in lysosomes or for release in exosomes, yet how prions impact proteostatic pathways is unclear. We found that prion-affected human and mouse brain showed a marked reduction in Hrs and STAM1 (ESCRT-0), which route ubiquitinated membrane proteins from early endosomes into MVBs. To determine how the reduction in ESCRT-0 impacts prion conversion and cellular toxicity in vivo , we prion-challenged conditional knockout mice (male and female) having Hrs deleted from neurons, astrocytes, or microglia. The neuronal, but not astrocytic or microglial, Hrs-depleted mice showed a shortened survival and an acceleration in synaptic derangements, including an accumulation of ubiquitinated proteins, deregulation of phosphorylated AMPA and metabotropic glutamate receptors, and profoundly altered synaptic structure, all of which occurred later in the prion-infected control mice. Finally, we found that neuronal Hrs (nHrs) depletion increased surface levels of the cellular prion protein, PrP C , which may contribute to the rapidly advancing disease through neurotoxic signaling. Taken together, the reduced Hrs in the prion-affected brain hampers ubiquitinated protein clearance at the synapse, exacerbates postsynaptic glutamate receptor deregulation, and accelerates neurodegeneration. SIGNIFICANCE STATEMENT Prion diseases are rapidly progressive neurodegenerative disorders characterized by prion aggregate spread through the central nervous system. Early disease features include ubiquitinated protein accumulation and synapse loss. Here, we investigate how prion aggregates alter ubiquitinated protein clearance pathways (ESCRT) in mouse and human prion-infected brain, discovering a marked reduction in Hrs. Using a prion-infection mouse model with neuronal Hrs (nHrs) depleted, we show that low neuronal Hrs is detrimental and markedly shortens survival time while accelerating synaptic derangements, including ubiquitinated protein accumulation, indicating that Hrs loss exacerbates prion disease progression. Additionally, Hrs depletion increases the surface distribution of prion protein (PrP C ), linked to aggregate-induced neurotoxic signaling, suggesting that Hrs loss in prion disease accelerates disease through enhancing PrP C -mediated neurotoxic signaling., (Copyright © 2023 the authors.)

As a pattern recognition receptor which activates innate immune system, toll-like receptor 2 (TLR2) has been reportedly mediates allergic airway inflammation (AAI), yet the underlying mechanism remains elusive. Here, in a murine AAI model, TLR2 -/- mice showed decreased airway inflammation, pyroptosis and oxidative stress. RNA-sequencing revealed that allergen-induced hif1 signaling pathway and glycolysis were significantly downregulated when TLR2 was deficient, which were confirmed by lung protein immunoblots. Glycolysis inhibitor 2-Deoxy-d-glucose (2-DG) inhibited allergen-induced airway inflammation, pyroptosis, oxidative stress and glycolysis in wild type (WT) mice, while hif1α stabilizer ethyl 3,4-dihydroxybenzoate (EDHB) restored theses allergen-induced changes in TLR2 -/- mice, indicating TLR2-hif1α-mediated glycolysis contributes to pyroptosis and oxidative stress in AAI. Moreover, upon allergen challenge, lung macrophages were highly activated in WT mice but were less activated in TLR2 -/- mice, 2-DG replicated while EDHB reversed such effect of TLR2 deficiency on lung macrophages. Likewise, both in vivo and ex vivo WT alveolar macrophages (AMs) exhibited higher TLR2/hif1α expression, glycolysis and polarization activation in response to ovalbumin (OVA), which were all inhibited in TLR2 -/- AMs, suggesting AMs activation and metabolic switch are dependent on TLR2. Finally, depletion of resident AMs in TLR2 -/- mice abolished while transfer of TLR2 -/- resident AMs to WT mice replicated the protective effect of TLR2 deficiency on AAI when administered before allergen challenge. Collectively, we suggested that loss of TLR2-hif1α-mediated glycolysis in resident AMs ameliorates allergic airway inflammation that inhibits pyroptosis and oxidative stress, therefore the TLR2-hif1α-glycolysis axis in resident AMs may be a novel therapeutic target for AAI., Competing Interests: Declaration of competing interest The authors have declared that no competing interest exists., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Porcine reproductive and respiratory syndrome virus (PRRSV) is major economic problem given its effects on swine health and productivity. Therefore, we evaluated the genetic stability of a codon pair de-optimized (CPD) PRRSV, E38-ORF7 CPD, as well as the master seed passage threshold that elicited an effective immune response in pigs against heterologous virus challenge. The genetic stability and immune response of every 10th passage (out of 40) of E38-ORF7 CPD was analyzed through whole genome sequencing and inoculation in 3-week-old pigs. E38-ORF7 CPD passages were limited to 20 based on the full-length mutation analysis and animal test results. After 20 passages, the virus could not induce antibodies to provide effective immunity and mutations accumulated in the gene, which differed from the CPD gene, presenting a reason for low infectivity. Conclusively, the optimal passage number of E38-ORF7 CPD is 20. As a vaccine, this may help overcome the highly diverse PRRSV infection with substantially enhanced genetic stability.

Commercially used porcine respiratory and reproductive syndrome (PRRS) modified live virus (MLV) vaccines provide limited protection with heterologous viruses, can revert back to a virulent form and they tend to recombine with circulating wild-type strains. Codon pair deoptimization (CPD) is an advanced method to attenuate a virus that overcomes the disadvantages of MLV vaccines and is effective in various virus vaccine models. The CPD vaccine against PRRSV-2 was successfully tested in our previous study. The co-existence of PRRSV-1 and -2 in the same herd demands protective immunity against both viruses. In this study, live attenuated PRRSV-1 was constructed by recoding 22 base pairs in the ORF7 gene of the E38 strain. The efficacy and safety of the CPD live attenuated vaccine E38-ORF7 CPD to protect against virulent PRRSV-1 were evaluated. Viral load, and respiratory and lung lesion scores were significantly reduced in animals vaccinated with E38-ORF7 CPD. Vaccinated animals were seropositive by 14 days post-vaccination with an increased level of interferon-γ secreting cells. In conclusion, the codon-pair-deoptimized vaccine was easily attenuated and displayed protective immunity against virulent heterologous PRRSV-1.

Itaconate has emerged as a novel anti-inflammatory and antioxidative endogenous metabolite, yet its role in allergic airway inflammation (AAI) and the underlying mechanism remains elusive. Here, the itaconate level in the lung was assessed by High Performance Liquid Chromatography (HPLC), and the effects of the Irg1/itaconate pathway on AAI and alveolar macrophage (AM) immune responses were evaluated using an ovalbumin (OVA)-induced AAI model established by wild type (WT) and Irg1 -/- mice, while the mechanism of this process was investigated by metabolomics analysis, mitochondrial/cytosolic protein fractionation and transmission electron microscopy in the lung tissues. The results demonstrated that the Irg1 mRNA/protein expression and itaconate production in the lung were significantly induced by OVA. Itaconate ameliorated while Irg1 deficiency augmented AAI, and this may be attributed to the fact that itaconate suppressed mitochondrial events such as NLRP3 inflammasome activation, oxidative stress and metabolic dysfunction. Furthermore, we identified that the Irg1/itaconate pathway impacted the NLRP3 inflammasome activation and oxidative stress in AMs. Collectively, our findings provide evidence for the first time, supporting the conclusion that in the allergic lung, the itaconate level is markedly increased, which directly regulates AMs' immune responses. We therefore propose that the Irg1/itaconate pathway in AMs is a potential anti-inflammatory and anti-oxidative therapeutic target for AAI.

The process of handling and bonding copper (Cu) and graphene inevitably creates defects. To use graphene/Cu composites as electronic devices with new physical properties, it is essential to evaluate the effect of such defects. Since graphene is an ultrathin anisotropic material having a hexagonal structure, an evaluation of graphene/Cu composites containing defects was conducted taking into account the inherent structural characteristics. The purpose of this study is to evaluate defects that may occur in the manufacturing process and to present a usable basic method for the stable design research and development of copper/graphene composites essential for commercialization of copper/graphene composites. In the future, when performing analytical calculations on various copper/graphene composites and defect shapes in addition to the defect conditions presented in this paper, it is considered that it can be used as a useful method considering defects that occur during application to products of desired thickness and size. Herein, density functional theory was used to evaluate the behavior of graphene/Cu composites containing defects. The density of states (DOS) values were also calculated. The analysis was implemented using three kinds of models comprising defect-free graphene and two- and four-layered graphene/Cu composites containing defects. DOS and Fermi energy levels were used to gage the effect of defects on electrical properties.

In this study, two nonsingular three-dimensional (3D) guidance strategies to intercept a stationary target with desired impact angles, subject to nonlinear coupled dynamics, field-of-view (FOV) limit and lateral acceleration bounds, are investigated. As a stepping stone, two novel sliding mode surfaces are designed, the convergence and boundedness of the two sliding mode surfaces can guarantee the impact-angle-constrained interception while maintaining the seeker's lock-on condition during the guidance. A novel auxiliary system is also presented to compensate for the effects caused by input saturation. In addition, the analytical achievable impact angles set is presented in terms of the initial engagement condition. Numerical simulations with various constraints, a realistic missile model and comparison study have been considered to show the feasibility and effectiveness of the proposed strategies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 ISA. Published by Elsevier Ltd. All rights reserved.)

In this study, the homojunction thin-film transistors (TFTs) with amorphous indium gallium zinc oxide (a-IGZO) as active channel layers and source/drain electrodes were fabricated by RF magnetron sputtering. The effect of oxygen partial pressure on the phase, microstructure, optical and electrical properties of IGZO thin films was investigated. The results showed that amorphous IGZO thin films always exhibit a high transmittance above 90% and wide band gaps of around 3.9 eV. The resistivity increases as the IGZO thin films are deposited at a higher oxygen partial pressure due to the depletion of oxygen vacancies. In addition, the electrical behaviors in homojunction IGZO TFTs were analyzed. When the active channel layers were deposited with an oxygen partial pressure of 1.96%, the homojunction IGZO TFTs exhibited optimal transfer and output characteristics with a field-effect mobility of 13.68 cm 2 V -1 s -1 . Its sub-threshold swing, threshold voltage and on/off ratio are 0.6 V/decade, 0.61 V and 10 7 , respectively., (© 2022 IOP Publishing Ltd.)

Organochalcogen heterocycles are ubiquitously present and widely utilized in various fields. Among them, oxirane has been extensively studied, and all of the stereoisomeric forms are readily available. In contrast, synthetic studies on thiirane were rarely reported, and thus the useful sulfur-congener of oxirane has been difficult to access in a stereodefined form. In this research, a general stereoselective synthesis of cis-thiiranes is accomplished by taking advantage of stereospecific electrocyclization of trans-thiocarbonyl ylides, which are generated in situ from readily available E,E-aldazine N-oxides upon treatment with Lawesson's reagent. This newly developed practical method provides a variety of cis-1,2-diarylthiiranes as essentially single diastereomers in high yields under mild reaction conditions. The intermediacy of trans-thiocarbonyl yilde is confirmed by mechanistic experiments, and the excellent stereocontrol is rationalized by DFT calculation., (© 2022. The Author(s).)

In this study, a porous titanium zirconium (TiZr)-based bulk metallic foam was successfully fabricated using the Cu spacer by employing the hot press method. TiZr-based bulk metallic foams with porosities ranging from 0% to 50% were fabricated and analyzed. The results indicate that thermal conductivity increased with the addition of Cu spacer; the increased thermal conductivity reduced the holding time in the hot press method. Moreover, the compressive strength decreased from 1261 to 76 MPa when the porosity of the TiZr-based bulk metallic foam increased to 50%, and the compressive strength was predictable. In addition, the foam demonstrated favorable biocompatibility in cell viability, cell migration capacity, and calcium deposition tests. Moreover, the pore size of the porous TiZr-based bulk metallic foam was around 120 µm. In conclusion, TiZr-based bulk metallic foam has favorable biocompatibility, mechanical property controllability, and porous structure for bone ingrowth and subsequent enhanced osteointegration. This porous TiZr-based bulk metallic foam has great potential as an orthopedic implant to enhance bone healing and decrease healing time.

Breathing can be heavily influenced by pain or internal emotional states, but the neural circuitry underlying this tight coordination is unknown. Here we report that Oprm1 (μ-opioid receptor)-expressing neurons in the lateral parabrachial nucleus (PBL) are crucial for coordinating breathing with affective pain in mice. Individual PBL Oprm1 neuronal activity synchronizes with breathing rhythm and responds to noxious stimuli. Manipulating PBL Oprm1 activity directly changes breathing rate, affective pain perception, and anxiety. Furthermore, PBL Oprm1 neurons constitute two distinct subpopulations in a "core-shell" configuration that divergently projects to the forebrain and hindbrain. Through non-overlapping projections to the central amygdala and pre-Bötzinger complex, these two subpopulations differentially regulate breathing, affective pain, and negative emotions. Moreover, these subsets form recurrent excitatory networks through reciprocal glutamatergic projections. Together, our data define the divergent parabrachial opioidergic circuits as a common neural substrate that coordinates breathing with various sensations and behaviors such as pain and emotional processing., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: LncRNA prostate cancer-associated transcript 6 (PCAT6) has been reported to be dysregulated in several cancers and is associated with tumor progression. Here, we have performed a meta-analysis to assess the general prognostic role of PCAT6 in malignancies., Methods: Four public databases (Embase, Pubmed, Web of Science, Cochrane Library) were used to identify eligible studies, then data was extracted and associations between prognostic indicators and clinical characteristics were combined to estimate hazard ratio (HR) or odds ratio (OR) with a 95% confidence interval (CI). Publication bias was measured using the Begg's test, and the stability of the combined results was measured using sensitivity analysis. Subsequently, results were validated using Gene Expression Profiling Interactive Analysis (GEPIA) and the National Genomics Data Center (NGDC)., Results: Ten studies were considered eligible for inclusion. In total, 937 patients and eight types of cancer were included. Our results revealed that overexpression of PCAT6 was significantly associated with a shorter OS (HR = 1.82; 95% CI, [1.40, 2.38]; P < 0.0001) and progression-free survival (PFS) (HR = 1.66; 95% CI, [1.22, 2.25]; P < 0.0001) in cancer patients, and that PCAT6 overexpression was significantly associated with individual tumor clinicopathological parameters, including TNM stage (OR = 0.29; 95% CI, [0.09, 0.94]; P = 0.04), gender (OR = 1.84; 95% CI, [1.31, 2.59]; P = 0.0005), and whether the tumor was metastatic (OR = 5.02; 95% CI, [1.36, 18.57]; P = 0.02). However, PCAT6 overexpression was not correlated with patient age and tumor differentiation. PCAT6 expression was significantly up-regulated in four types of cancer, which was validated using the GEPIA cohort. Combining OS and disease-free survival (DFS) of these four types of cancer revealed a shorter OS and DFS in patients with PCAT6 overexpression. PCAT6 expression in various types of cancer was also validated in NGDC. A total of eight cancers were analyzed and PCAT6 was highly expressed in all eight cancers. Further functional predictions suggest that PCAT6 is correlated with tumor prognosis, and that PCAT6 may be useful as a new tumor-specific marker., Conclusions: LncRNA PCAT6 is highly expressed in multiple cancer types and its upregulation was significantly associated with patient prognosis and poorer clinical features, thereby suggesting that PCAT6 may be a novel prognostic factor in multiple cancer types., (© 2021. The Author(s).)

Background: The National Comprehensive Cancer Network's Rectal Cancer Guideline Panel recommends American Joint Committee of Cancer and College of American Pathologists (AJCC/CAP) tumor regression grading (TRG) system to evaluate pathologic response to neoadjuvant chemoradiotherapy for locally advanced rectal cancer (LARC). Yet, the clinical significance of the AJCC/CAP TRG system has not been fully defined., Materials and Methods: This was a multicenter, retrospectively recruited, and prospectively maintained cohort study. Patients with LARC from one institution formed the discovery set, and cases from external independent institutions formed a validation set to verify the findings from discovery set. Overall survival (OS), disease-free survival (DFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were assessed by Kaplan-Meier analysis, log-rank test, and Cox regression model., Results: The discovery set (940 cases) found, and the validation set (2,156 cases) further confirmed, that inferior AJCC/CAP TRG categories were closely /ccorrelated with unfavorable survival (OS, DFS, LRFS, and DMFS) and higher risk of disease progression (death, accumulative relapse, local recurrence, and distant metastasis) (all p < .05). Significantly, pairwise comparison revealed that any two of four TRG categories had the distinguished survival and risk of disease progression. After propensity score matching, AJCC/CAP TRG0 category (pathological complete response) patients treated with or without adjuvant chemotherapy displayed similar survival of OS, DFS, LRFS, and DMFS (all p > .05). For AJCC/CAP TRG1-3 cases, adjuvant chemotherapy treatment significantly improved 3-year OS (90.2% vs. 84.6%, p < .001). Multivariate analysis demonstrated the AJCC/CAP TRG system was an independent prognostic surrogate., Conclusion: AJCC/CAP TRG system, an accurate prognostic surrogate, appears ideal for further strategizing adjuvant chemotherapy for LARC., Implications for Practice: The National Comprehensive Cancer Network recommends the American Joint Committee of Cancer and College of American Pathologists (AJCC/CAP) tumor regression grading (TRG) four-category system to evaluate the pathologic response to neoadjuvant treatment for patients with locally advanced rectal cancer; however, the clinical significance of the AJCC/CAP TRG system has not yet been clearly addressed. This study found, for the first time, that any two of four AJCC/CAP TRG categories had the distinguished long-term survival outcome. Importantly, adjuvant chemotherapy may improve the 3-year overall survival for AJCC/CAP TRG1-3 category patients but not for AJCC/CAP TRG0 category patients. Thus, AJCC/CAP TRG system, an accurate surrogate of long-term survival outcome, is useful in guiding adjuvant chemotherapy management for rectal cancer., (© 2021 AlphaMed Press.)

Throughout the past 2020, the pandemic COVID-19 has caused a big global shock, meanwhile it brought a great impact on the public health network. Trauma emergency system faced a giant challenge and how to manage trauma under the pandemic of COVID-19 was widely discussed. However, the trauma treatment of special population (geriatric patients and patients taking anticoagulant drugs) has received inadequate attention. Due to the high mortality following severe traumatic hemorrhage, hemostasis and trauma-induced coagulopathy are the important concerns in trauma treatment. Sepsis is another topic should not be ignored when we talking about trauma. COVID-19 itself is a special kind of sepsis, and it may even be called as serious systemic infection syndrome. Sepsis has been become a serious problem waiting to be solved urgently no matter in the fields of trauma, or in intensive care and infection, etc. This article reviewed the research progress in areas including trauma emergency care, trauma bleeding and coagulation, geriatric trauma and basic research of trauma within 2020., (Copyright © 2021. Production and hosting by Elsevier B.V.)

Foodborne protein hydrolysates exhibit biological activity that may be therapeutic in a number of human disease settings. Hemp peptides (HP) generated by controlled hydrolysis of hemp proteins have a number of health benefits and are of pharmaceutical value. In the present study, we produce small molecular weight HP from hemp seed and investigate its anticancer properties in Hep3B human liver cancer cells. We demonstrate that HP treatment increased apoptosis, reduced cell viability, and reduced cell migration in Hep3B human liver cancer cells without affecting the normal liver cell line L02. We correlate these phenotypes with increased cellular ROS levels, upregulation of cleaved caspase 3 and Bad, and downregulation of antiapoptotic Bcl-2. HP treatment led to increased Akt and GSK-3β phosphorylation, with subsequent downregulation of β-catenin, suggesting β-catenin signaling modulation as a critical mechanism by which HP exhibits anticancer properties. Our findings suggest HP are of potential therapeutic interest for liver cancer treatment., Competing Interests: The authors declare no conflicts of interest., (© 2021 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.)

The year 2020 is an extremely unusual year. The world lost more than one million lives due to the attack of COVID-19. Economic production has been greatly reduced, and daily activities are largely restricted. Luckily the work of Chinese Journal of Traumatology (CJTEE) has not been adversely affected. 2020 is a harvest year for the journal, which (1) was included in the high-quality academic journals by China Association for Science and Technology; (2) cover of each issue is newly designed; (3) submission increased by about 60% with more countries and regions covered; (4) usage in the ScienceDirect database exceeded a million; (5) the CiteScore rises to more than 2.0 the first time. This study reviewed the articles published in the year 2020 by CJTEE., Competing Interests: Declaration of competing interest The authors declare no competing interest., (Copyright © 2020. Production and hosting by Elsevier B.V.)

Background: Stiff-person syndrome (SPS) is a rare autoimmune neurologic disease characterized by painful rigidity and muscle spasms. Patients with SPS may present with psychiatric symptoms, and little is known about the presence of psychiatric comorbidities., Objective: The objective of this study was to provide an overview of the association between SPS and psychiatric illnesses., Methods: The protocol is registered in PROSPERO (Registration ID CRD42020159354). Peer-reviewed articles on adults with SPS and psychiatric comorbidities published before May 26, 2020, were selected by 2 independent reviewers. Qualitative summary data and relative risk of psychiatric disorders in patients with SPS compared with the general population and multiple sclerosis were calculated., Results: After screening 909 articles, 52 full texts were assessed for eligibility and 27 were ultimately included, 5 of which were selected for quantitative analysis. Although limited by small sample sizes leading to large confidence intervals, the relative risk of any psychiatric comorbidity in SPS was higher than that of the general population, ranging from estimates of 6.09 (95% confidence interval: 4.09, 9.08) to 11.25 (95% confidence interval: 3.27, 38.66). There was no statistically significant difference in the risk of any psychiatric comorbidity between SPS and multiple sclerosis. The review also highlighted delays in SPS diagnosis, often related to misattribution of symptoms as being solely secondary to a psychiatric cause., Conclusions: The higher risk of psychiatric comorbidities emphasizes the important role of psychiatrists in recognizing the symptoms of SPS to reach timely diagnosis and treatment. The presence of psychiatric symptoms should support rather than delay the diagnosis of SPS., (Copyright © 2020 Academy of Consultation-Liaison Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: To study effects of postoperative regular training of core muscle strength guided by the concept of enhanced recovery after surgery (ERAS) on the rehabilitation of elderly patients with osteoporotic lumbar vertebral compression fracture after vertebroplasty (PVP) and kyphoplasty(PKP)., Methods: Ninety-four elderly patients with osteoporotic lumbar compression fractures who underwent PKP or PVP from January 2016 to January 2018 and met inclusion criteria were divided into observation group and control group. All the patients were treated with routine anti osteoporosis therapy after operation. There were 47 patients in the observationgroup, including 18 males and 29 females, with an average age of (62.62±3.21) years old;in the control group, there were 47 cases, including 17 males and 30 females, with an average age of (62.38±2.84) years old. The patients in the control group were trained by traditional way, and the patients in observation group were instructed to conduct regular training of core muscle strength according to ERAS concept. The patients were followed up for 1, 3 and 6 months after operation. Patients' conditions were quantitatively evaluated according to Barthel scale, JOA low back pain score and Oswestry Disability Index, and the differences in treatment effects between two groups were statistically analyzed and compared., Results: All the patients were followed up, and the Barthel scale, JOA low back pain score and Oswestry Disability Index score of the observation group were all better than those of the control group on the 1st and the 3rd months after surgery( P < 0.05). The Oswestry Disability Index score of the observation group on the 6th month after surgery were superior to those of the control group ( P <0.05). However, there was no significantly difference in JOA low back pain score and Barthel scale between two groups at 6 months after surgery ( P >0.05). The comparison of Barthel scale, JOA low back pain score and Oswestry Disability Index before and after the operation of 1, 3 and 6 months between the two groups were significantly improved ( P <0.05)., Conclusion: Early regular core strength training has a positive effect on early functional recovery and improvement of life ability after PKP or PVP for elderly patients with osteoporotic lumbar compression fractures, which is in line with the concept of accelerated rehabilitation surgery.

Context: Curcumin has shown efficacy in promoting radiosensitivity combined with radiotherapy. However, the role and mechanism of curcumin on radiosensitivity in laryngeal squamous cell cancer (LSCC) is largely unknown. Objective: The aim of our study is to explore the role of IKKγ-NF-κB signaling in curcumin enhancing LSCC cell radiosensitivity in vitro . Materials and methods: Curcumin and X-ray were used to induce cell DNA damage and apoptosis, or inhibit cell clone formation. IKKγ siRNA and plasmid were used to change IKKγ expression. The CCK8 assay was used to detect cell viability. Clone formation ability was analyzed using a clonogenic assay, cell apoptosis was examined using flow cytometry, an immunofluorescence assay was used to detect DNA damage, while mRNA and protein levels were assayed using real time PCR and western blotting, respectively. Results: Curcumin significantly enhanced irradiation-induced DNA damage and apoptosis, while weakening clone-forming abilities of LSCC cell line Hep2 and Hep2-max. Compared to Hep2 cells, Hep2-max cells are more sensitive to curcumin post-irradiation. Curcumin suppressed irradiation-induced NF-κB activation by suppressing IKKγ expression, but not IKKα and IKKβ. Overexpression of IKKγ decreased irradiation-induced DNA damage and apoptosis, while promoting clone-forming abilities of Hep2 and Hep2-max cells. IKKγ overexpression further increased expression of NF-κB downstream genes, Bcl-XL, Bcl-2, and cyclin D1. Conversely, IKKγ silencing enhanced irradiation-induced DNA damage and apoptosis, but promoted clone formation in Hep2 and Hep2-max cells. Additionally, IKKγ silencing inhibited expression of Bcl-XL, Bcl-2, and cyclin D1. Conclusions: Curcumin enhances LSCC radiosensitivity via NF-ΚB inhibition by suppressing IKKγ expression.

(1) Background: The purpose of this study is to examine the relationship between social support in the workplace for childcare teachers, resilience, and self-care. This study explores the inner mechanism that helps to strengthen self-care of childcare teachers, which enables teachers to provide quality care to children and promote their own wellbeing. (2) Methods: The survey was conducted from September to October 2018 for childcare teachers in Seoul and Gyeonggi Province using convenience sampling. Out of 550 questionnaires, 491 were returned, with 466 used for the analysis, excluding those with incomplete responses. The collected data were analyzed using descriptive statistics, correlation analysis, and mediation analysis. (3) Results: There were significant correlations between all variables. The mediation analysis showed a complete mediation of resilience. (4) Conclusion: Childcare teachers first have to take good care of themselves in order to perform well as a childcare professional. Educational materials and counseling programs tailored for childcare teachers need to be developed for better self-care and building greater resilience. Materials for directors of daycare centers, as well as teachers stressing the importance of social support for each other, will help childcare teachers' effective functioning in their professional and personal life. Prevention and intervention programs for self-care will eventually help lower the costs of healthcare in society.

Objective: From the perspective of clinical application to analyze the effectiveness and reliability of CPC/PMMA bone cement in percutaneous kyphoplasty (PKP) for the treatment of elderly patients with osteoporotic thoracolumbar fractures., Methods: A retrospective analysis was performed on 62 patients with osteoporotic compression fracture of single-vertebral thoracic or lumbar segment who underwent PKP surgery and had a bone density less than or equal to -3.0 SD from February 2016 to December 2016. Among them, 23 patients were in CPC/PMMA group, with an average age of (77.6±2.2) years old, 39 patients in PMMA group, with an average age of (77.1±1.1) years old. The indexes between two groups were compared, including the visual analogue scale (VAS), height ratio of anterior vertebra (AVHR), local Cobb angle, cement leakage, new adjacent vertebral fracture(NAVF)., Results: There were no significant difference in gender, age, follow-up time and preoperative VAS, AVHR, local Cobb angle between two groups ( P >0.05), at the 1 day after operation, VAS, AVHR, local Cobb angle in all patients got obvious improvement ( P <0.05), which was no significant difference at 1 day after operation and final follow-up ( P >0.05). At the same time, there was no statistically significant difference in the incidence of new adjacent vertebral fracture and cement leakage ( P >0.05). The pain in both groups continued to improve at follow up after operation ( P <0.05), the local Cobb angle increased ( P <0.05) and AVHR decreased slightly ( P <0.05). However, the images of conventional methods (X-ray or CT) could not find signs about CPC degeneration and new bone ingrowth., Conclusion: CPC/PMMA composite bone cement is safe and reliablein PKP for treatment of elderly patients with osteoporotic thoracolumbar fractures, which can effectively relieve pain and maintain vertebral body stability. It has the same curative effect as PMMA bone cement. It was worthy to research more in future, although no direct evidences support the CPC/PMMA composite bone cement can reduce the incidence of adjacent vertebral fracture, CPC degeneration or new bone ingrowth.

The prevention and treatment of chronic inflammation using food-derived compounds are desirable from the perspectives of marketing and safety. Monascus pigments, widely used as food additives, can be used as a chronic inflammation treatment. Orange Monascus pigments were produced by submerged fermentation in a 5 L bioreactor, and multiple orange Monascus pigment derivatives with anti-inflammatory activities were synthesized using aminophilic reaction. A total of 41 types of pigment derivatives were produced by incorporating amines and amino acids into the orange pigments. One derivative candidate that inhibited nitric oxide (NO) production in Raw 264.7 cells and exhibited low cell cytotoxicity was identified via in vitro assay. The 2-amino-4 picoline derivative inhibited NO production of 48.4%, and exhibited cell viability of 90.6%. Expression of inducible NO synthase, an important enzyme in the NO synthesis pathway, was suppressed by such a derivative in a dose-dependent manner. Therefore, this derivative has potential as a functional food colorant with anti-inflammatory effects.

Mg-based bulk metallic glass (BMG) and its composites have been promising candidates for orthopedic fixation implants because of their biocompatibility, low degradation rate, and osteogenic potential. However, the amorphous state is affected by the cooling rate during the casting process. Solid, unstable structures combined with amorphous and crystalline structures are generated when an insufficient cooling rate is used. Here, we aimed to design and synthesize a novel core-shell structure comprising an amorphous shell and a crystalline core in order to overcome the material size limit imposed by the cooling rate effects. Our results show that the core-shell structure of Mg-based BMG does have a lower degradation rate and can maintain a more amorphous structure after six weeks of degradation. Moreover, the biocompatibility and osteogenic effects were similar between the core-shell and solid structures of Mg-based BMG. In conclusion, the core-shell structure of Mg-based BMG exhibits a lower degradation rate while still enhancing osteogenic potential in vitro. This core-shell structure of Mg-based BMG overcomes the cooling rate effects and provides a new structure for manufacturing Mg-based BMG., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

CuCrO 2 is one of the most promising p-type transparent conductive oxide (TCO) materials. Its electrical properties can be considerably improved by Mg doping. In this work, Cr-deficient CuCrO 2 thin films were deposited by reactive magnetron sputtering based on 5 at.% Mg doping. The influence of Cr deficiency on the film's optoelectronic properties was investigated. As the film's composition varied, CuO impurity phases appeared in the film. The mixed valency of Cu + /Cu 2+ led to an enhancement of the hybridization between the Cu 3d and O 2p orbitals, which further reduced the localization of the holes by oxygen. As a result, the carrier concentration significantly improved. However, since the impurity phase of CuO introduced more grain boundaries in Cu[Cr 0.95-x Mg 0.05 ]O 2 , impeding the transport of the carrier and incident light in the film, the carrier mobility and the film's transmittance reduced accordingly. In this work, the optimal optoelectronic performance is realized where the film's composition is Cu[Cr 0.78 Mg 0.05 ]O 2 . Its Haacke's figure of merit is about 1.23 × 10 -7 Ω -1 .

A series of biocompatible high-porosity (up to 72.4%) TiZr-based porous bulk metallic glass (BMG) scaffolds were successfully fabricated by hot pressing a mixture of toxic element-free TiZr-based BMG powder and an Al particle space holder. The morphology of the fabricated scaffolds was similar to that of human bones, with pore sizes ranging from 75 to 250 μm. X-ray diffraction patterns and transmission electron microscopy images indicated that the amorphous structure of the TiZr-based BMG scaffolds remained in the amorphous state after hot pressing. Noncytotoxicity and extracellular calcium deposition of the TiZr-based BMG scaffolds at porosities of 32.8%, 48.8%, and 64.0% were examined by using the direct contact method. The results showed that the BMG scaffolds possess high cell viability and extracellular calcium deposition with average cell survival and deposition rates of approximately 170.1% and 130.9%, respectively. In addition, the resulting TiZr-based BMG scaffolds exhibited a considerable reduction in Young's moduli from 56.4 to 2.3 GPa, compressive strength from 979 to 19 MPa, and bending strength from 157 MPa to 49 MPa when the porosity was gradually increased from 2.0% to 72.4%. Based on the aforementioned specific characteristics, TiZr-based BMG scaffolds can be considered as potential candidates for biomedical applications in the human body.

The indication of bloodletting therapy was determined based on the multi-dimensional evidence assessment, which could provide guidance for the clinical application of bloodletting therapy. The literature of bloodletting therapy was comprehensively collected by retrieval in CNKI, Wanfang and VIP databases (until February 23, 2019), modern books in Library of Tianjing University of TCM and the Chinese Medical Code (Fifth Edition). The disease spectrum of bloodletting therapy was determined by self-designed questionnaire survey e-mailed to relevant experts. The indication of bloodletting therapy was determined by Delphi expert meeting. As a result, 746 pieces of ancient literature and 32 775 modern literature were included. The indications of bloodletting therapy based on the multi-dimensional evidence assessment include herpes zoster, acne, acute tonsillitis, vascular headache, varicose veins of lower extremities, acute lumbar sprain, early erysipelas, wheat swelling, exogenous fever of children, stroke, which are mainly the syndromes of blood stasis, toxin, excess and heat.

Mg-based bulk metallic glass materials have been investigated for their large potential for application in orthopedic implants due to their biocompatibility, low degradation rate, and osteogenetic ability. As an orthopedic implant, initial cell adhesion has been a critical issue for subsequent osteogenesis and bone formation because the first contact between cells and the implant occurs upon the implants surface. Here, we aimed to create Mg-based bulk metallic glass samples with three different surface roughness attributes in order to understand the degradation behavior of Mg-based bulk metallic glass and the adhesion ability and osteogenetic ability of the contact cells. It was found that the degradation behavior of Mg 66 Zn 29 Ca 5 bulk metallic glass was not affected by surface roughness. The surface of the Mg 66 Zn 29 Ca 5 bulk metallic glass samples polished via #800 grade sandpaper was found to offer a well-attached surface and to provide a good cell viability environment for Human MG63 osteoblast-like cell line. In parallel, more calcium and mineral deposition was investigated on extracellular matrix with higher surface roughness that verify the relationship between surface roughness and cell performance.

Obesity is a major health problem and is known to be closely associated with metabolic diseases. Abnormal hepatic accumulation of fat causes fatty liver or hepatic steatosis, and long-term consumption of a high-fat diet is known to be a key obesity-causing factor. Recent studies have demonstrated that probiotics such as Lactobacillus strains, exert an anti-obesity effect by regulating adipogenesis. However, it is still unknown how the consumption of probiotics can reduce abdominal fat volume by regulating the hepatic expression of lipogenic genes. Therefore, we evaluated the effect of long-term ingestion of L. plantarum LMT1-48 on the expression of lipogenic genes in high-fat diet (HFD)-fed mice. We observed that treatment of 3T3-L1 adipocytes with L. plantarum LMT1-48 extract inhibited their differentiation and lipid accumulation by downregulating lipogenic genes, namely, PPARγ, C/EBPα, FAS, and FABP4. Interestingly, administration of L. plantarum LMT1-48 reduced liver weight and liver triglycerides concurrently with the downregulation of the lipogenic genes PPARγ, HSL, SCD-1, and FAT/CD36 in the liver, resulting in the reduction of body weight and fat volume in HFD-fed obese mice. Notably, we also observed that the administration of at least 10 6 CFU of L. plantarum LMT1-48 significantly lowered body weight and abdominal fat volume in modified diet-fed mouse models. Collectively, these data suggest that L. plantarum LMT1-48 is a potential healthy food for obese people.

The most successful therapeutic strategies for locally advanced cancers continue to combine decades-old classical radiosensitizing chemotherapies with radiotherapy. Molecular targeted radiosensitizers offer the potential to improve the therapeutic ratio by increasing tumor-specific kill while minimizing drug delivery and toxicity to surrounding normal tissue. Auristatins are a potent class of anti-tubulins that sensitize cells to ionizing radiation damage and are chemically amenable to antibody conjugation. To achieve tumor-selective radiosensitization, we synthesized and tested anti-HER2 antibody-drug conjugates of two auristatin derivatives with ionizing radiation. Monomethyl auristatin E (MMAE) and monomethyl auristatin F (MMAF) were attached to the anti-HER2 antibodies trastuzumab and pertuzumab through a cleavable linker. While MMAE is cell permeable, MMAF has limited cell permeability as free drug resulting in diminished cytotoxicity and radiosensitization. However, when attached to trastuzumab or pertuzumab, MMAF was as efficacious as MMAE in blocking HER2-expressing tumor cells in G 2 -M. Moreover, MMAF anti-HER2 conjugates selectively killed and radiosensitized HER2-rich tumor cells. Importantly, when conjugated to targeting antibody, MMAF had the advantage of decreased bystander and off-target effects compared with MMAE. In murine xenograft models, MMAF anti-HER2 antibody conjugates had less drug accumulated in the normal tissue surrounding tumors compared with MMAE. Therapeutically, systemically injected MMAF anti-HER2 conjugates combined with focal ionizing radiation increased tumor control and improved survival of mice with HER2-rich tumor xenografts. In summary, our results demonstrate the potential of cell-impermeable radiosensitizing warheads to improve the therapeutic ratio of radiotherapy by leveraging antibody-drug conjugate technology., (©2019 American Association for Cancer Research.)

Background: Mobile rehabilitation systems for patients with gait disorder are being developed. Safety functions to prevent patients from falling are considered during product development; however, few studies have been conducted on systems that have been prevalidated for healthy adults prior to application to patients., Objective: This study analyzed the characteristics of lower extremity muscles and foot pressure in healthy adults during unbalanced walking with differences in the speed of left and right speed using a two-belt treadmill., Methods: Twenty subjects performed gait motions with a difference in the weight support conditions (0% and 30%) and the left and right lower limb speeds (1-3 km/h). Each subject's muscular activities and foot pressure signals were collected. The gait patterns of the faster side exhibit similar characteristics to the paralyzed leg, and the slower side is similar to the non-paralyzed leg., Results: Weight-supporting healthy subjects showed asymmetric gait patterns, similar to hemiplegic patients, because of the difference in the speed of the left and right side., Conclusions: The quantitative results can be used to develop a training protocol for two-belt treadmills with differently controlled left and right speeds for gait rehabilitation in hemiplegic patients.

In the present study, the efficacy of unilateral transverse process-pedicle and bilateral puncture techniques in percutaneous kyphoplasty (PKP) for Kummell disease was compared. Between March 2015 and June 2017, 63 patients with Kummell disease were recruited and underwent PKP with two different puncture techniques: A total of 38 patients were treated by unilateral transverse process-pedicle PKP and 25 patients were treated by bilateral PKP. The operative time, intra-operative fluoroscopy time, volume of bone cement injection and bone cement leakage were recorded. Prior to surgery and 1 day post-surgery, the visual analogue scale (VAS) pain score and Oswestry disability index (ODI) were determined, and the vertebral body height and Cobb angle were measured. The results indicated that the incidence of bone cement leakage in the unilateral group was similar with the bilateral group (15.79% vs. 16.00%), with no statistically significant difference between the two groups. None of the patients in the two groups had any obvious damage of the spinal cord. The operative time, intra-operative fluoroscopy time and volume of bone cement injection in the unilateral group were lower than those in the bilateral group. A chest X-ray examination at 1 day post-surgery revealed no pulmonary embolism in the two groups. The VAS score, ODI, vertebral body height and Cobb angle were significantly improved in the unilateral and bilateral groups at 1 day post-surgery and at the last follow-up (12 months post-surgery) as compared with these parameters prior to surgery. In conclusion, the unilateral transverse process-pedicle and bilateral puncture techniques in PKP exhibited good efficacy as a treatment for Kummell disease. The operative time, intra-operative fluoroscopy time and volume of bone cement injection were lower in the unilateral group., (Copyright © 2019, Spandidos Publications.)

Background: Few studies have investigated the role of decongestive therapy and high-flow nasal cannula (HFNC) in preventing reintubation and in-hospital mortality in patients with acute cardiogenic pulmonary edema (ACPE)., Methods: Data from patients with ACPE who were weaned from mechanical ventilation in the cardiac intensive care unit between January 2013 and December 2017 were retrospectively evaluated. All patients were treated with HFNC or conventional oxygen therapy (COT), such as a nasal cannula or venturi mask, immediately after extubation. Decongestive therapy (intravenous furosemide infusion) was administered at the discretion of the attending physician., Results: Of 212 patients treated during the study period, 47 were excluded due to recent open-heart surgery and two, due to insufficient clinical data. The remaining 163 patients had a mean age of 67.4±14.3 years, and 92 (56.4%) were male; 44 patients received HFNC, and 119 COT. Mean weight loss within 72 hours of extubation was -0.86±2.03 kg. A total of 38 patients (23.3%) required reintubation, 21 of whom (12.9%) required reintubation within 72 hours of extubation. In-hospital mortality occurred in 16 patients (9.8%). Multivariate analysis showed that weight increase within 72 hours of extubation was independent determinants of reintubation (OR =1.7; 95% CI: 1.2-2.2; P<0.001) and in-hospital mortality (OR =1.5; 95% CI: 1.1-2.1; P=0.005). The use of HFNC was not associated with reintubation or in-hospital mortality., Conclusions: Our findings indicate that early weight loss resulted in reduced reintubation and in-hospital mortality in patients with ACPE. However, HFNC and COT did not differ in the prevention of reintubation and in-hospital mortality. Therefore, aggressive decongestive therapy, rather than HFNC, should be considered early after extubation., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (2019 Journal of Thoracic Disease. All rights reserved.)