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Liang Chen,1 Xiu-Di Han,2 Yan-Li Li,3 Chun-Xiao Zhang,4 Xi-Qian Xing5 1Department of Infectious Diseases, Beijing Jishuitan Hospital, 4th Medical College of Peking University, Beijing, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, Qingdao Municipal Hospital, Qingdao City, Shandong Province, People’s Republic of China; 3Department of Infectious Diseases and Clinical Microbiology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Department of Pulmonary and Critical Care Medicine, Beijing Huimin Hospital, Beijing, People’s Republic of China; 5Department of Pulmonary and Critical Care Medicine, The 2nd People’s Hospital of Yunnan Province, Kunming City, Yunnan Province, People’s Republic of ChinaCorrespondence: Liang Chen Tel +8613810438037Email chenliang1995@sina.comPurpose: Respiratory viruses are important etiologies of community-acquired pneumonia (CAP). However, the impact of different RVs on the outcomes of CAP is not well elucidated. This study aims to compare the clinical features and severity of influenza (Flu-p) and non-influenza respiratory viruses-related pneumonia (NIRVs-p) onset in the community among immunocompetent adults.Methods: The data of the patients hospitalized with laboratory-confirmed RVs-p were retrospectively reviewed from five teaching hospitals in China from January 2013 to May 2019. Univariate and multivariate logistic regressions were performed to compare the clinical characteristics and outcomes between Flu-p and NIRVs-p.Results: A total of 1079 patients with Flu-p and 341 patients with NIRVs-p were included in this study. A multivariate logistic regression model revealed chronic pulmonary disease [odd ratio (OR) 0.341, 95% confidence interval (CI) 0.225– 0.515, p < 0.001], solid malignant tumor (OR 0.330, 95% CI 0.163– 0.668, p = 0.002), myalgia (OR 1.697, 95% CI 1.236– 2.330, p < 0.001), lymphocytes < 0.8× 109/L (OR 10.811, 95% CI 6.949– 16.818, p < 0.001) and blood albumin < 35 g/L (OR 0.327, 95% CI 0.242– 0.442, p < 0.001) were predictors for Flu-p. After adjusting for confounders, the multivariate logistic regression analysis confirmed that influenza B-related pneumonia (FluB-p) (OR 0.419, 95% CI 0.272– 0.646, p < 0.001) and NIRVs-p (OR 0.260, 95% CI 0.158– 0.467, p < 0.001) were associated with a decreased risk of 30-day mortality compared with the influenza A-related pneumonia (FluA-p).Conclusion: Our results showed that patients with FluA-p experience a more severe disease than those with FluB-p and NIRVs-p. Some clinical features are helpful to distinguish between NIRVs-p and Flu-p.Keywords: influenza, respiratory virus, pneumonia, clinical characteristics, severity

Xiang-Dong Han,1 Zhi-Wei Zhou,2–4 Wei Yang,1 Hang-Cheng Ye,1 Ying-Zi Xu,1 Yun-Feng Huang,1 Tong Zhang,1 Shu-Feng Zhou2 1School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, USA; 3Guizhou Provincial Key Laboratory for Regenerative Medicine, 4Stem Cell and Tissue Engineering Research Center and Sino-US Joint Laboratory for Medical Sciences, Guizhou Medical University, Guiyang, People’s Republic of China Abstract: Ischemic heart disease (IHD) is the leading cause of death worldwide and remains a major life-threatening factor in humans. Apoptosis has been implicated in the pathogenesis of IHD. The Chinese herbal formula Huo Luo Xiao Ling Dan (HLXLD), one of the commonly used Chinese herbal formulas, consists of Salviae miltiorrhizae, Angelica sinensis, Gummi olibanum, and Commiphora myrrha, with a wide spectrum of pharmacological activity. However, the mechanism of action and molecular targets of HLXLD in the treatment of IHD are unclear. This study aimed to computationally predict the molecular interactions between the major active components of HLXLD and key regulators of apoptosis and then examine the effect of HLXLD on coronary artery ligation-induced acute myocardial ischemia in rats. The molecular interactions between the major active components of HLXLD, including ferulic acid, ligustilide, succinic acid, vanillic acid, tanshinone IIA, tanshinone IIB, danshensu, salvianolic acid A, salvianolic acid C, protocatechuic aldehyde, and β-boswellic acid and human protein molecules including B cell lymphoma-extra large (Bcl-xl), B cell lymphoma 2 antagonist/killer 1 (Bak1), B cell lymphoma 2 (Bcl-2), procaspase 3, and caspase 9 with regard to hydrogen bond formation, charge interaction, and π-π stacking using Discovery Studio® program 3.1. The 12 HLXLD components were predicted by ADMET (absorption, distribution, metabolism, excretion and toxicity) Predictor to have favorable pharmacokinetic and low hepatotoxicity profiles. The acute myocardial ischemia was established by surgical ligation of the left anterior descending coronary artery. The rats were divided into a sham operative group, a model group, a positive control group treated with 0.2 mg/kg isosorbide mononitrate, and groups treated with 2.7, 5.4, or 10.8 g/kg HLXLD. The results showed that administration of HLXLD increased mean arterial pressure, left ventricular systolic pressure, heart rate, and maximal rate of rise/descent of left ventricular pressure levels. Administration of HLXLD significantly ameliorated coronary artery ligation-induced tissue damage in the left ventricle, with restored arrangement of myocardial fibers and recovered myoplasm in rats. Furthermore, HLXLD markedly increased the expression level of Bcl-2 but decreased the level of cleaved caspase 3. Taken together, administration of HLXLD attenuated acute myocardial ischemia-induced damage in cardiomyocytes and inhibited apoptotic death of cardiomyocytes, thereby exerting a cardioprotective effect in rats with IHD. These findings suggest that HLXLD may represent a promising herbal formula for the treatment of cardiovascular disease by counteracting apoptotic cell death via multiple active compounds. More studies are warranted to fully elucidate the mechanisms of action, identify the therapeutic targets, and validate the efficacy and safety of HLXLD in the treatment of IHD. Keywords: Huo Luo Xiao Ling Dan, myocardial ischemia, coronary artery ligation, hemodynamics, apoptosis, molecular docking

Rationale: Cardiac arrest (CA) is a life-threatening event with a high mortality rate, and neurological injury following cardiopulmonary resuscitation (CPR) is a leading cause of death and disability in survivors. While prolonged CPR is often associated with poor neurological outcomes, there is limited evidence of successful recovery following extended resuscitation efforts. This study aims to highlight the potential for recovery after prolonged CPR by reporting a case of a patient who underwent 152 minutes of CPR, regained consciousness, and made a full recovery. The purpose is to explore whether advanced life-support techniques, such as extracorporeal CPR (ECPR), can improve survival and neurological outcomes even after prolonged CA., Patient Concerns: A 53-year-old man with no prior health issues experienced sudden CA while exercising and underwent prolonged CPR., Diagnoses: Restoration of spontaneous circulation following CA and ventricular fibrillation., Interventions: ECPR, target temperature management, continuous renal replacement therapy, and intracranial pressure management., Outcomes: Immediate recovery: following the restoration of spontaneous circulation, the patient was immediately transferred to the intensive care unit for further treatment. Despite the prolonged CPR duration, the patient remained hemodynamically stable and was able to tolerate the intensive interventions. Neurological recovery: after 1 week of intensive therapy, the patient regained consciousness. Initially, there was some confusion and disorientation, but he gradually became fully alert, oriented, and communicative. Neurological assessments indicated no significant long-term deficits, and brain imaging showed no signs of irreversible damage. Cardiological and renal recovery: cardiac function was closely monitored, with no evidence of significant ischemic damage to the myocardium. The patient's renal function improved with continuous renal replacement therapy, and kidney function returned to normal following the discontinuation of dialysis. Discharge: after 2 weeks of treatment in the intensive care unit and a transfer to the cardiology department for rehabilitation, the patient was discharged from the hospital. He had fully recovered both neurologically and physiologically, with no residual deficits., Lessons: This case demonstrates that prolonged CPR, when combined with advanced interventions such as ECPR, can result in favorable outcomes, including survival and neurological recovery. The findings suggest that with timely and appropriate treatment, even patients with extended resuscitation efforts may achieve full recovery, thus underscoring the potential of ECPR as a critical life-saving intervention in cases of prolonged CA., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2025 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Food addiction and an impulsive personality can increase overeating, which can lead to weight gain. The amygdala and nucleus accumbens (NAcc) are critical for regulating obesogenic behaviour. However, whether the amygdala or the NAcc acts as the neural basis for the regulation of food addiction, impulsive personality, and body weight remains unclear., Methods: We examined the differences in the volume of the amygdala and NAcc, especially the lateralization index (LI), between 33 obese participants and 39 age- and sex-matched healthy controls. The associations of the LI of each brain region with clinical variables and body mass index (BMI) were identified using network analysis. Finally, we explored the relationships among the LIs of brain regions, impulsive personality, food addiction, and BMI through a multiple chain mediation model., Results: We observed a significant decrease in the LI of the amygdala in the obese group compared with the healthy group (F = 20.276, p < 0.001), which indicates that the right amygdala was larger than the left amygdala in the obese group. Network analysis revealed that the LI of the amygdala was very closely associated with nonplanning impulsivity, food addiction and BMI. The results of the mediation analysis indicated that increased nonplanning impulsiveness could lead to weight gain through increased food addiction (β = 0.069, SE = 0.043, 95% CI [0.014, 0.184]). Moreover, in this symptom chain, the LI of the amygdala can mediate the relationship between food addiction and BMI (β = 0.018, SE = 0.014, 95% CI [0.002, 0.061])., Conclusion: Our observations indicate a substantial reduction in the LI of the amygdala among individuals with obesity, suggesting a structural predisposition. The findings reveal a potential neural mechanism that can help explain the interplay between impulsivity, food addiction, and obesity.

Background: General anesthesia is commonly used in the surgical management of gastrointestinal tumors; however, it can lead to emergence agitation (EA). EA is a common complication associated with general anesthesia, often characterized by behaviors, such as crying, struggling, and involuntary limb movements in patients. If treatment is delayed, there is a risk of incision cracking and bleeding, which can significantly affect surgical outcomes. Therefore, having a proper understanding of the factors influencing the occurrence of EA and implementing early preventive measures may reduce the incidence of agitation during the recovery phase from general anesthesia, which is beneficial for improving patient prognosis., Aim: To analyze influencing factors and develop a risk prediction model for EA occurrence following general anesthesia for primary liver cancer., Methods: Retrospective analysis of clinical data from 200 patients who underwent hepatoma resection under general anesthesia at Wenzhou Central Hospital (January 2020 to December 2023) was conducted. Post-surgery, the Richmond Agitation-Sedation Scale was used to evaluate EA presence, noting EA incidence after general anesthesia. Patients were categorized by EA presence postoperatively, and the influencing factors were analyzed using logistic regression. A nomogram-based risk prediction model was constructed and evaluated for differentiation and fit using receiver operating characteristics and calibration curves., Results: EA occurred in 51 (25.5%) patients. Multivariate analysis identified advanced age, American Society of Anesthesiologists (ASA) grade III, indwelling catheter use, and postoperative pain as risk factors for EA ( P < 0.05). Conversely, postoperative analgesia was a protective factor against EA ( P < 0.05). The area under the curve of the nomogram was 0.972 [95% confidence interval (CI): 0.947-0.997] for the training set and 0.979 (95%CI: 0.951-1.000) for the test set. Hosmer-Lemeshow test showed a good fit ( χ 2 = 5.483, P = 0.705), and calibration curves showed agreement between predicted and actual EA incidence., Conclusion: Age, ASA grade, catheter use, postoperative pain, and analgesia significantly influence EA occurrence. A nomogram constructed using these factors demonstrates strong predictive accuracy., Competing Interests: Conflict-of-interest statement: The authors declare no conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: Melanoma, with its high degree of malignancy, stands as one of the most dangerous skin cancers and remains the primary cause of death from skin cancer. With studies demonstrating the potential of traditional Chinese medicine to intervene and treat melanoma, we turned our attention to celastrol. Celastrol is a triterpene compound extracted from the traditional Chinese medicine derived from Tripterygium wilfordii. Previous studies have shown that celastrol exerts inhibitory effects on various malignant tumors, including melanoma. Hence, our goal was to clarify the impact of celastrol on cell viability, apoptosis, and cell cycle progression by elucidating its effects on the PI3K/AKT/mTOR pathway., Methods: CCK-8 and wound healing assays were used to determine the effect of celastrol on the viability and migration of B16-F10 cells. Changes in cell apoptosis, cell cycle, reactive oxygen species (ROS), and mitochondrial membrane potential were detected by flow cytometry. PI3K/AKT/mTOR pathway proteins and HIF-α mRNA expression in B16-F10 cells were detected by western blotting and qPCR. Moreover, the addition of a PI3K activator demonstrated that celastrol could inhibit the function of B16-F10 cells via the PI3K/AKT/mTOR pathway., Results: Celastrol inhibited the viability and migration of B16-F10 cells. Through the inhibition of the PI3K/AKT/mTOR pathway down-regulates the expression of HIF-α mRNA, thereby causing an increase of ROS in cells and a decrease in the mitochondrial membrane potential to promote cell apoptosis and cell cycle arrest. The inhibitory effect of celastrol on B16-F10 cells was further demonstrated by co-culturing with a PI3K activator., Conclusion: Celastrol inhibits the function of B16-F10 cells by inhibiting the PI3K/AKT/mTOR cellular pathway and regulating the expression of downstream HIF-α mRNA., (© 2024. The Author(s).)

Drinking water treatment sludge (DWTS) is a by-product of water treatment, and it is difficult to recycle to high value and poses potential environmental risks. Recycling DWTS into cement-based materials is an effective measure to achieve its high-volume utilization and reduce its environmental load. DWTS is rich in silica-alumina phases and has potential pozzolanic activity after drying, grinding and calcination, giving it similar properties to traditional supplementary cementitious materials. Adjusting the sludge production process and coagulant type will change its physical and chemical properties. Adding a small amount of DWTS can generate additional hydration products and refine the pore structure of the cement sample, thus improving the mechanical properties and durability of the sample. However, adding high-volume DWTS to concrete causes microstructural deterioration, but it is feasible to use high-volume DWTS to produce artificial aggregates, lightweight concrete, and sintered bricks. Meanwhile, calcined DWTS has similar compositions to clay, which makes it a potential raw material for cement clinker production. Cement-based materials can effectively solidify heavy metal ions in DWTS, and alkali-activated binders, magnesium-based cement, and carbon curing technology can further reduce the risk of heavy metal leaching. This review provides support for the high-value utilization of DWTS in cement-based materials and the reduction of its potential environmental risks., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Ventricular arrhythmias (VAs) mainly occur in the early post-myocardial infarction (MI) period. However, studies examining the association between total myocardial ischemia time interval and the risk of new-onset VAs during a long-term follow-up are scarce., Methods: This study (symptom-to-balloon time and VE ntricular a R rh Y thmias in patients with STEMI , VERY-STEMI study) was a multicenter, observational cohort and real-world study, which included patients with ST-segment elevation MI (STEMI) undergoing percutaneous coronary intervention (PCI). The primary endpoint was cumulative new-onset VAs during follow-up. The secondary endpoints were the major adverse cardiovascular events (MACE) and changes in left ventricular ejection fraction (ΔLVEF, %)., Results: A total of 517 patients with STEMI were included and 236 primary endpoint events occurred. After multivariable adjustments, compared to patients with S2BT of 24 h-7d, those with S2BT ≤ 24 h and S2BT > 7d had a lower risk of primary endpoint. RCS showed an inverted U-shaped relationship between S2BT and the primary endpoint, with an S2BT of 68.4 h at the inflection point. Patients with S2BT ≤ 24 h were associated with a lower risk of MACE and a 4.44 increase in LVEF, while there was no significant difference in MACE and LVEF change between the S2BT > 7d group and S2BT of 24 h-7d group., Conclusions: S2BT of 24 h-7d in STEMI patients was associated with a higher risk of VAs during follow-up. There was an inverted U-shaped relationship between S2BT and VAs, with the highest risk at an S2BT of 68.4 h., 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: Hepatocellular carcinoma (HCC) remains a leading life-threatening health challenge worldwide, with pressing needs for novel therapeutic strategies. Sphingosine kinase 1 (SphK1), a well-established pro-cancer enzyme, is aberrantly overexpressed in a multitude of malignancies, including HCC. Our previous research has shown that genetic ablation of Sphk1 mitigates HCC progression in mice. Therefore, the development of PF-543, a highly selective SphK1 inhibitor, opens a new avenue for HCC treatment. However, the anti-cancer efficacy of PF-543 has not yet been investigated in primary cancer models in vivo, thereby limiting its further translation., Methods: Building upon the identification of the active form of SphK1 as a viable therapeutic target in human HCC specimens, we assessed the capacity of PF-543 in suppressing tumor progression using a diethylnitrosamine-induced mouse model of primary HCC. We further delineated its underlying mechanisms in both HCC and endothelial cells. Key findings were validated in Sphk1 knockout mice and lentiviral-mediated SphK1 knockdown cells., Results: SphK1 activity was found to be elevated in human HCC tissues. Administration of PF-543 effectively abrogated hepatic SphK1 activity and significantly suppressed HCC progression in diethylnitrosamine-treated mice. The primary mechanism of action was through the inhibition of tumor neovascularization, as PF-543 disrupted endothelial cell angiogenesis even in a pro-angiogenic milieu. Mechanistically, PF-543 induced proteasomal degradation of the critical glycolytic enzyme 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3, thus restricting the energy supply essential for tumor angiogenesis. These effects of PF-543 could be reversed upon S1P supplementation in an S1P receptor-dependent manner., Conclusions: This study provides the first in vivo evidence supporting the potential of PF-543 as an effective anti-HCC agent. It also uncovers previously undescribed links between the pro-cancer, pro-angiogenic and pro-glycolytic roles of the SphK1/S1P/S1P receptor axis. Importantly, unlike conventional anti-HCC drugs that target individual pro-angiogenic drivers, PF-543 impairs the PFKFB3-dictated glycolytic energy engine that fuels tumor angiogenesis, representing a novel and potentially safer therapeutic strategy for HCC., (© 2024. The Author(s).)

Background: Waist circumference can be used as an anthropometric measure to assess central obesity and is easier and more convenient than the waist-to-hip ratio in identifying the risk of obesity and medical problems. Most studies showing an association between obesity and infertility in women have used BMI to measure obesity. Our goal was to examine any potential association between waist circumference and infertility., Methods: This cross-sectional study, which formed part of the National Health and Nutrition Examination Survey (NHANES), comprised women ages 18 to 45 between 2017 and 2020. Participants without waist circumference data or information on infertility were removed from the study. The independent relationship between waist circumference and infertility was investigated using weighted binary logistic regression and subgroup analysis., Results: We investigated 1509 participants and discovered that the prevalence of infertility rose as the WC trisection rose. (tertile 1, 7.55%; tertile 2, 10.56%; tertile 3, 15.28%; trend < 0.001). Multivariate logistic regression showed that after total adjustment, higher WC levels were associated with an increased likelihood of infertility in women (OR1.02; 95% CI 1.01-1.03), and There was a 2% rise in the incidence of infertility for every unit (cm) increased WC. Subgroup analysis and interaction tests showed no significant dependence of the effects of marital status, diabetes, hypertension, and high cholesterol on the association between WC and infertility ( p for all interaction tests > 0.05). The inflection point of the positive non-linear relationship between WC and infertility was 116.6 cm., Conclusion: Excessive waist circumference assessment may increase the probability of infertility, and more attention should be paid to the management of waist circumference should be given more attention., 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 © 2023 Yin, Zhou, Lu, Chen, Liu, Lu, Han and Wu.)

Background: Combinatorial immunotherapy strategies for enhancing the responsiveness of immune system have shown great promise for cancer therapy. Engineered nanoformulation incorporated toll-like receptor (TLR) 9 agonist CpG ODN has shown more positive results in suppressing tumor growth and can significantly enhance other immunotherapy activity with combinatorial effects due to the innate and adaptive immunostimulatory effects of CpG., Results: In the present work, protamine sulfate (PS) and carboxymethyl β-glucan (CMG) were used as nanomaterials to form nanoparticles through a self-assembly approach for CpG ODN encapsulation to generate CpG ODN-loaded nano-adjuvant (CNPs), which was subsequently mixed with the mixture of mouse melanoma-derived antigens of tumor cell lysates (TCL) and neoantigens to develop vaccine for anti-tumor immunotherapy. The obtained results showed that CNPs was able to effectively deliver CpG ODN into murine bone marrow-derived dendritic cells (DC) in vitro, and remarkably stimulate the maturation of DC cells with proinflammatory cytokine secretion. In addition, in vivo analysis showed that CNPs enhanced anti-tumor activity of PD1 antibody and CNPs-adjuvanted vaccine based on the mixture antigens of melanoma TCL and melanoma-specific neoantigen could not only induce anti-melanoma cellular immune responses, but also elicit melanoma specific humoral immune responses, which significantly inhibited xenograft tumor growth. Furthermore, CD16 CAR-T cells were generated by expressing CD16-CAR in CD3 + CD8 + murine T cells., Conclusion: Our results eventually showed that anti-melanoma antibodies induced by CNPs-adjuvanted TCL vaccines were able to collaborate with CD16-CAR-T cells to generate an enhanced targeted anti-tumor effects through ADCC (antibody dependent cell cytotoxicity) approach. CD16 CAR-T cells has thus a great potential to be an universal promising strategy targeting on solid tumor synergistic immunotherapy via co-operation with TCL-based vaccine., (© 2023. The Author(s).)

Background: Left ventricular thrombus is a rare condition, for which appropriate treatments are not extensively studied. Although it can be treated by thrombectomy, such surgery can be difficult and risky, and not every patient can tolerate the surgery., Case Summary: We report a case of a middle-aged man receiving veno-arterial extracorporeal membrane oxygenation (VA-ECMO) for acute myocardial infarction who developed left ventricular thrombus despite systemic anticoagulation. After systemic thrombolysis with urokinase, the left ventricular thrombus disappeared, ECMO was successfully withdrawn 9 days later, and the patient recovered and was discharged from hospital., Conclusion: Systemic thrombolysis is a treatment option for left ventricular thrombus in addition to anticoagulation and thrombectomy., Competing Interests: Conflict-of-interest statement: All the authors declare that they have no conflict of interest., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

For eutrophic water bodies, potassium permanganate is an effective pre-oxidant to remove algae and its residue in water treatment sludge. Recycling water treatment sludge in concrete is an environmentally friendly and high-value utilization measure. However, little research has been done on the effect of manganese-rich drinking water sludge ash (DWSA) on concrete. The effect of water-binder ratio (w/b) on strength, shrinkage and microstructural characteristics of concrete containing DWSA was investigated, and the structural behavior was explained from a nanoscale perspective. The results show that recycling 10 % DWSA in concrete improved the strength and shrinkage resistance of the samples. Reducing the w/b effectively increased the strength of DWSA-modified concrete and reduced the shrinkage deformation. The paste with high w/b had higher contents of non-evaporated water and calcium hydroxide, as well as higher reaction degree of DWSA. Nanoscale characterization shows that reducing the w/b reduced the volume fraction of pore and unhydrated phases in the matrix and increased the proportion of high-density C-S-H. Meanwhile, reducing the w/b also reduced the interfacial transition zone width of DWSA-modified concrete. Recycling DWSA in concrete effectively reduced the total carbon footprint and cost of the mixture. The combined application of reducing the w/b and incorporating DWSA effectively improved the economic and environmental benefits of concrete material. For the concrete modified with 10 % DWSA (w/b = 0.3), its cost and carbon emissions are reduced by 14 %-21 % and 19 %-25 % compared with the reference sample, respectively. Overall, this study reveals the action mechanism of DWSA in cement system at different w/b from nanoscale perspective, and gives a new insight on determining the optimal w/b in full-scale application of DWSA concrete., 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 B.V. All rights reserved.)

Cue-induced food cravings are strong desires directed toward specific foods, usually ones with high caloric content, and can lead to overeating. However, although food cravings vary according to individual preferences for specific high-calorie food subtypes, a structured library of food craving-inducing pictures including multiple categories of high-calorie foods does not yet exist. Here, we developed and validated a picture library of Chinese foods (PLCF) consisting of five subtypes of high-calorie foods (i.e., sweets, starches, salty foods, fatty foods, and sugary drinks) to allow for more nuanced future investigations in food craving research, particularly in Chinese cultural contexts. We collected 100 food images representing these five subtypes, with four food items per subtype depicted in five high-resolution photographs each. We recruited 241 individuals with overweight or obesity to rate the food pictures based on craving, familiarity, valence, and arousal dimensions. Of these participants, 213 reported the severity of problematic eating behaviors as a clinical characteristic. Under the condition of mixing multiple subtypes of high-calorie foods, we did not observe significant differences in craving ratings for high- and low-calorie food images ( p tukey > 0.05). Then, we compared each subtype of high-calorie food images to low-calorie ones, and found craving ratings were greater for the images of salty foods and sugary drinks ( ps < 0.05). Furthermore, we conducted a subgroup analysis of individuals according to whether they did or did not meet the criteria for food addiction (FA) and found that greater cravings induced by the images of high-calorie food subtypes (i.e., salty foods and sugary drinks) only appeared in the subgroup that met the FA criteria. The results show that the PLCF is practical for investigating food cravings., 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 © 2023 Cai, Zhang, Zheng, Xu, Liu, Ban, Di, Yuan and Han.)

Objectives: Excessive accumulation of adipose tissue may accelerate brain aging, but the underlying mechanisms are poorly understood. Several adiposity indices were proposed to assess obesity, while their linkage with brain health in older adults remained unclear. Here we aimed to examine the associations of adiposity indices with global and regional cerebral blood flow (CBF) in older adults, while considering insulin resistance., Design: This was a cross-sectional population-based study that included older adults derived from the baseline participants in the ongoing Multimodal Interventions to Delay Dementia and Disability in rural China (MIND-China) study., Setting and Participants: The study included 103 Chinese rural-dwelling older adults (age≥60 years; 69.9% women) who underwent brain magnetic resonance imaging scans., Methods: We estimated eight adiposity indices based on anthropometric measures. We automatically quantified global and regional CBF using the arterial spin labeling scans. Insulin resistance was assessed using the triglyceride-glucose index and then dichotomized into high and low levels according to the median. Data were analyzed using general linear model and voxel-wise analysis., Results: Of the eight examined adiposity indices, only higher waist-to-height ratio (WHtR) and body roundness index (BRI) were associated with reduced global CBF (multivariable-adjusted β-coefficients and 95%CI: -1.76; -3.25, -0.27 and -1.77; -3.25, -0.30, respectively) and hypoperfusion in bilateral middle temporal gyri, angular gyri and superior temporal gyri, left middle cingulum and precuneus (P<0.05). There were statistical interactions of WHtR and BRI with levels of insulin resistance on CBF, such that the significant associations of higher WHtR and BRI with lower global and regional CBF existed only in people with high insulin resistance (P<0.05)., Conclusion: Higher WHtR and BRI are associated with cerebral hypoperfusion in older adults, especially in people with high insulin resistance. This may highlight the pathological role of visceral fat in vascular brain aging., Competing Interests: All authors declare no conflicts of interest.

Hepatocellular carcinoma (HCC) accounts for 90% of primary liver cancer, the third leading cause of cancer-associated death worldwide. With the increasing prevalence of metabolic conditions, non-alcoholic fatty liver disease (NAFLD) is emerging as the fastest-growing HCC risk factor, and it imposes an additional layer of difficulty in HCC management. Dysregulated hepatic lipids are generally believed to constitute a deleterious environment cultivating the development of NAFLD-associated HCC. However, exactly which lipids or lipid regulators drive this process remains elusive. We report herein that sphingosine kinase 2 (SphK2), a key sphingolipid metabolic enzyme, plays a critical role in NAFLD-associated HCC. Ablation of Sphk2 suppressed HCC development in NAFLD livers via inhibition of hepatocyte proliferation both in vivo and in vitro. Mechanistically, SphK2 deficiency led to downregulation of ceramide transfer protein (CERT) that, in turn, decreased the ratio of pro-cancer sphingomyelin (SM) to anti-cancer ceramide. Overexpression of CERT restored hepatocyte proliferation, colony growth and cell cycle progression. In conclusion, the current study demonstrates that SphK2 is an essential lipid regulator in NAFLD-associated HCC, providing experimental evidence to support clinical trials of SphK2 inhibitors as systemic therapies against HCC., (© 2022. The Author(s).)

The present study revealed that palmitic acid (PA) treatment induced epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells, which are involved in the progression of proliferative vitreoretinopathy (PVR). ARPE-19 cells were treated with PA followed by miRNA screening and EMT marker detection using qRT-PCR. Then, miR-124 mimic or inhibitor was transfected into ARPE-19 cells to explore the role of miR-124 on the EMT of ARPE-19 cells using transwell assay. The underlying mechanism of miRNA were predicted by bioinformatics method and confirmed by luciferase activity reporter assay. Furthermore, gain-of-function strategy was also used to explore the role of LIN7C in the EMT of ARPE-19 cells. The expression of miRNA or mRNA expression was determined by qRT-PCR and the protein expression was determined using western blot assay. The result presented that PA reduced the expression of E-cadherin/ZO-1 whilst increasing the expression of fibronectin/α-SMA. In addition, PA treatment enhanced the expression of microRNA (miR)-124 in ARPE-19 cells. Overexpression of miR-124 enhanced PA-induced upregulation of E-cadherin and ZO-1 expression and downregulation of fibronectin and α-SMA. Moreover, miR-124 mimic also enhanced the migration of ARPE-19 cells induced by PA treatment. Inversely, miR-124 inhibitor presented opposite effect on PA-induced EMT and cell migration in ARPE-19 cells. Luciferase activity reporter assay confirmed that Lin-7 homolog C (LIN7C) was a direct target of miR-124 in ARPE-19 cells. Overexpression of LIN7C was found to suppress the migration ability and expression of fibronectin and α-SMA, while increasing expression of E-cadherin and ZO-1; miR-124 mimic abrogated the inhibitive effect of LIN7C on the EMT of ARPE-19 cells and PA further enhanced this abolishment. Collectively, these findings suggest that miR-124/LIN7C can modulate EMT and cell migration in RPE cells, which may have therapeutic implications in the management of PVR diseases., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Han et al.)

Impulsiveness is a stable personal characteristic that contributes to obesity and may interact with it. Specifically, obesity is caused by unrestrained impulse eating that is not consciously controlled and leads to a hormonal imbalance that also can impair impulse control. However, the mechanism of this relationship is unclear. In our study, 35 obese individuals (body mass index, BMI > 28) were recruited and matched with 31 healthy controls (BMI < 24) in age and education level. All the participants underwent a resting-state fMRI and completed the Barratt Impulsiveness Scale-11. The results showed that patients with obesity had a significantly lower fractional amplitude of low-frequency fluctuations (fALFF) in the bilateral dorsolateral prefrontal cortex (dlPFC) and higher fALFF in the left fusiform cortex. In addition, non-planning impulsiveness was positively correlated with BMI. Importantly, we found that the right dlPFC completely mediated the relationship between non-planning impulsiveness and BMI. Our findings suggest that impulsivity is statistically more likely to precede obesity than to precede impulsivity and contributes to obesity by downregulating spontaneous activity in the dlPFC. This suggests that the dlPFC, which is associated with executive control, may be able a potential target for treating obesity., Competing Interests: QL was employed in Siemens Healthcare Ltd. The remaining 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 © 2022 Han, Zhang, Xu, Liu, Cai, Liu, Li, Zheng, Xu and Yuan.)

We report here that polysubstituted cyclopent-2-enols can be constructed by the one-pot reaction of doubly activated cyclopropanes and α-EWG substituted acetonitriles under mild basic conditions via a domino-ring-opening-cyclization/deacylation/oxidation sequence. Moreover, the synthetic applications of these cyclopent-2-enols have been demonstrated in the late-stage derivatization into functionalized cyclopentapyrimidin-4-ones and 2-hydroxy cyclopentanones with good yields.

Introduction: Sepsis is a primary cause of death in critically ill patients and is characterized by multiple organ dysfunction, including sepsis-induced acute kidney injury (AKI), which contributes to high mortality in sepsis. However, its pathophysiological mechanisms remain unclear. The kidney has one of the richest and most diversified endothelial cell populations in the body. This study was designed to investigate the effects of endothelial dysfunction in sepsis-induced AKI and explore possible intervention measures to offer new insight into the pathogenesis and treatment of sepsis-induced AKI., Methods: The circulating levels of endothelial adhesion molecules were detected in patients with sepsis and healthy controls to observe the role of endothelial damage in sepsis and sepsis-induced AKI. A murine sepsis model induced by cecal ligation and perforation was pretreated with a phosphoinositide 3-kinase gamma (PI3Kγ) inhibitor (CZC24832), and survival, kidney damage, and renal endothelial injury were assessed by pathological examination, immunohistochemistry, quantitative polymerase chain reaction, and Western blotting. Lipopolysaccharides and CZC24832 were administered to human umbilical vein endothelial cells in vitro, and endothelial cell function and the expression of adhesion molecules were evaluated., Results: Endothelial damage was more serious in sepsis-induced AKI than that in non-AKI, and the inhibition of PI3Kγ alleviates renal endothelial injury in a murine sepsis model, protecting endothelial cell function and repairing endothelial cell injury through the Akt signaling pathway., Conclusions: In this study, endothelial cell dysfunction plays an important role in sepsis-induced AKI, and the inhibition of PI3Kγ alleviates endothelial cell injury in sepsis-induced AKI through the PI3Kγ/Akt pathway, providing novel targets for treating sepsis and related kidney injury., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Periodontitis is an inflammatory disease resulting from subgingival microorganisms. Human periodontal ligament stem cells (hPDLSCs) can be applied in periodontal tissue regeneration. This study investigated the effect of hPDLSC-derived extracellular vesicles (EVs) on periodontitis. hPDLSC-derived EVs were isolated and identified. The murine model of periodontitis was established by ligation, and the cell model of periodontitis was established by treatment of macrophages with lipopolysaccharide (LPS). The effects of EVs on macrophage pyroptosis and periodontal inflammatory injury were measured by the means of HE staining, detection of LDH content, CCK-8 assay, Calcein-AM/PI staining, ELISA, Western blot, as well as measurement of caspase-1, SOD, and MDA. miR-590-3p expression was detected using RT-qPCR. miR-590-3p expression was then intervened to validate the effect of miR-590-3p on macrophage pyroptosis. The binding relationship between miR-590-3p and TLR4 was verified using dual-luciferase assay. Functional rescue experiment was performed to validate the role of TLR4 in macrophage pyroptosis. The results showed that inflammatory levels and macrophage pyroptosis were enhanced in the in vivo and in vitro models of periodontitis, evidenced by the increased NLRP3, GSDMD-N, caspase-1, IL-1β, IL-18, TNF-α, and MDA and decreased IL-10 and SOD. EVs alleviated periodontal inflammatory injury and macrophage pyroptosis. Physiologically, EVs carried miR-590-3p into macrophages to upregulate miR-590-3p expression and thereby suppress TLR4 transcription. miR-590-3p silencing or TLR4 overexpression reduced the inhibitory effect of EVs on macrophage pyroptosis. Collectively, EVs carried miR-590-3p into macrophages to subsequently inhibit TLR4 transcription, thereby reducing macrophage pyroptosis and alleviating periodontal inflammatory injury., (© 2021 S. Karger AG, Basel.)

K. galanga is an aromatic medicinal herb. It is locally to India and distributed in China, Myanmar, Indonesia, Malaysia, and Thailand. K. galanga is a Traditional Chinese Herb Medicine (TCHM), which has been applied to treat cold, dry cough, toothaches, rheumatism, hypertension and so on. In addition, it has been used widely as spices since its highly aromas. The aim of this review is to compile and update the current progresses of ethnomedicinal uses, phytochemistry, pharmacology and toxicology of K. galanga . All the data on K. galanga were based on different classical literary works, multiple electronic databases including SciFinder, Web of Science, PubMed, etc. The results showed that ninety-seven compounds have been identified from rhizome of K. galanga , including terpenoids, phenolics, cyclic dipeptides, flavonoids, diarylheptanoids, fatty acids and esters. Modern pharmacology studies revealed that extracts or secondary metabolites of the herb possessed anti-inflammatory, anti-oxidant, anti-tumorous, anti-bacterial, and anti-angiogenesis effects, which were closely related to its abundant ethnomedicinal uses. In conclusion, although previous research works have provided various information of K. galanga , more in-depth studies are still necessary to systemically evaluate phytochemistry, pharmacological activities, toxicity and quality control of this herb., 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 © 2021 Wang, Zhao, Xu, Han, Wu, Xu, Yang, Göransson and Liu.)

Background: Pseudomyxoma peritonei (PMP) is a rare mucinous neoplasm with a relatively low incidence of 1 to 2 per million individuals. It is typically characterized by a type of gelatinous ascites named "jelly belly". Most cases of PMP occur in association with ruptured primary mucinous tumors of the appendix (90%). Periodically, PMP can originate from mucinous carcinomas at other sites, including the colorectum, gallbladder, and pancreas. However, unusual origin can occur, as noted in this case report., Case Summary: A 52-year-old woman had an unusual derivation of PMP from intestinal duplication. The patient complained of abdominal distension and increasing abdominal girth. Abdominal contrast-enhanced computed tomography showed a mass in the greater omentum located on the left side of the abdomen, likely to be a cystic mass of peritoneal origin. A PMP diagnosis was presumed based on the specific signs of the mass with flocculent and stripe-like echoes in ultrasound images. Ultrasound-guided percutaneous aspiration suggested a high likelihood of PMP. Once the PMP diagnosis was recognized, identification of the origin of the primary tumor was indicated. Thus, an exploratory laparoscopy was performed. In the absence of a primary tumor of appendix origin, the diagnosis of a low-grade mucinous neoplasm of intestinal duplication origin was finally confirmed by histopathology., Conclusion: PMP is secondary to mucinous carcinomas of the appendix mostly. This case resulted from an unusual derivation from intestinal duplication., Competing Interests: Conflict-of-interest statement: All authors report no conflicts of interest related to this manuscript., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Smoking and Candida albicans (C. albicans) infection are risk factors for many oral diseases. Several studies have reported a close relationship between smoking and the occurrence of C. albicans infection. However, the exact underlying mechanism of this relationship remains unclear. We established a rat infection model and a C. albicans-Leuk1 epithelial cell co-culture model with and without smoke exposure to investigate the mechanism by which smoking contributes to C. albicans infection. Oral mucosa samples from healthy individuals and patients with oral leucoplakia were also analysed according to their smoking status. Our results indicated that smoking induced oxidative stress and redox dysfunction in the oral mucosa. Smoking-induced Nrf2 negatively regulated the NLRP3 inflammasome, impaired the oral mucosal defence response and increased the oral mucosa susceptibility to C. albicans. The results suggest that the Nrf2 pathway could be involved in the pathogenesis of oral diseases by mediating an antioxidative response to cigarette smoke exposure and suppressing host immunity against C. albicans., (© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

We report here that a series of bridged O,O-ketal fused spiro piperidone-cyclopropane derivatives 3 can be constructed with excellent yields and good diastereoselectivity by the one-pot reaction of 1-acylcyclopropanecarboxamides 1 with electron-deficient alkene 2a (EWG = CHO) via the domino process involving [4 + 2] annulation/intermolecular electrophilic addition/intramolecular cyclization. Furthermore, reactions of 1 with 2b/2c (EWG = CN, COOMe), leading to spiro piperidone-cyclopropane derivatives 4 or 5 by base catalyst selection, were also presented.

The screening of marker compound is of great significance to the quality control of traditional Chinese medicine (TCM). One approach which combines fingerprint and biological evaluation has developed rapidly. Multi-wavelength fusion fingerprints and antioxidant activity screening are integrated in this study to evaluate the quality of NAODESHENG. Characteristic multiwavelength fusion fingerprints of 14 batches of samples were generated at five different wavelengths and evaluated by quantitative fingerprinting with ultra-performance liquid chromatography (UPLC). In the quantitative fingerprinting method, 21 components in NAODESHENG were qualitatively and quantitatively analyzed by external standard method. The antioxidant activities of these 21 components was determined by pre-column antioxidant activity test. Multivariate statistical methods such as hierarchical clustering analysis and principal component analysis(PCA) was used to reduce the dimensions and variables from a large number of original data to screening marker compound with bioactivity. Based on the above results, it is suggested that 3'-Methoxy Puerarin and 11 other components should be used as the quality marker of NAODESHENG. This study demonstrates the feasibility of multi-wavelength fusion fingerprinting combined with antioxidant activity analysis, which associates quality control with bioactivity, providing a reliable and efficient method for quantitative assessment of TCM quality consistency., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Liver failure has high mortality and poor prognosis, and establishing new reliable markers for predicting its prognosis is necessary. Mucosal-associated invariant T (MAIT) cells are a novel population of innate-like lymphocytes involved in inflammatory liver disease, and their potential role in liver failure remains unclear., Aim: To investigate alteration of circulating MAIT cells and assess its prognostic value in patients with hepatitis B virus (HBV)-related liver failure., Methods: We recruited 55 patients with HBV-related liver failure, 48 patients with chronic hepatitis B and 40 healthy controls (HCs) from Nantong Third People's Hospital Affiliated to Nantong University. Peripheral blood mononuclear cells were isolated, and the percentage and number of circulating MAIT cells were detected by flow cytometry. Plasma levels of interleukin (IL)-7, IL-12p70, IL-18 and interferon-α were measured by Luminex assay., Results: Circulating MAIT cells were significantly decreased in HBV-related liver failure patients (percentage: 2.00 ± 1.22 vs 5.19 ± 1.27%, P < 0.0001; number: 5.47 ± 4.93 vs 84.43 ± 19.59, P < 0.0001) compared with HCs. More importantly, there was a significant reduction of MAIT cells in patients with middle/late-stage compared with early-stage liver failure. Circulating MAIT cells partially recovered after disease improvement, both in percentage (4.01 ± 1.21 vs 2.04 ± 0.95%, P < 0.0001) and in cell count (17.24 ± 8.56 vs 7.41 ± 4.99, P < 0.0001). The proportion (2.29 ± 1.01 vs 1.58 ± 1.38%, P < 0.05) and number (7.30 ± 5.70 vs 2.94 ± 1.47, P < 0.001) of circulating MAIT cells were significantly higher in the survival group than in the dead/liver transplantation group, and the Kaplan-Meier curve showed that lower expression of circulating MAIT cells (both percentage and cell count) predicted poor overall survival ( P < 0.01). Also, the levels of IL-12 (20.26 ± 5.42 pg/mL vs 17.76 ± 2.79 pg/mL, P = 0.01) and IL-18 (1470.05 ± 1525.38 pg/mL vs 362.99 ± 109.64 pg/mL, P < 0.0001) were dramatically increased in HBV-related liver failure patients compared with HCs., Conclusion: Circulating MAIT cells may play an important role in the process of HBV-related liver failure and can be an important prognostic marker., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest to report., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Ethnopharmacological Relevance: Tripterygium wilfordii Hook F. (TwHF), a traditional Chinese herb medicine, has been widely used for clinical treatment of various rheumatic immune diseases. Tripterygium glycosides (TG) extracted from TwHF has been verified to process multiple bioactivities, including immunosuppressive, anti-inflammatory and anti-cancer effects. However, the clinical application of TG is limited due to its severe toxicity and narrow therapeutic window. For the clinical safety of TG usage, attenuation of toxicity is the key issue to be solved., Purpose: Tripterygium glycoside fraction n2 (TG-n2) is a detoxified mixture obtained from TG using a new preparation method. In our previous study, we have demonstrated that TG-n2 has a lower toxicity than TG. The aim of the present study was to screen the renal protective effect of TG-n2 in nephrotic syndrome (NS) induced by adriamycin (ADR) in rats and its effect on apoptosis, as well as the effective difference between TG-n2 and TG., Materials and Methods: The ADR-induced NS rat model was established. Rats were intravenously injected with ADR (6 mg/kg), then treated with either TG-n2 (10 mg/kg/day) or TG (10 mg/kg/day) by oral gavage for 4 weeks. Clinical indexes in each group were determined. HE staining and electron microscopic analysis were used to evaluate renal histopathological damage. Caspase-3 activity reagent and TUNEL staining were used to estimate renal apoptosis. Protein levels of caspase-3, caspase-9, caspase-8, caspase-12, Bax, Bcl-2, p53, TNF-R1, FLIP and podocin were measured by Western Blot., Results: TG-n2 and TG intervention ameliorated renal function as assessed by the levels of 24-h proteinuria, Cr, BUN, TC, TG, ALB and LDL-c. TG-n2 and TG alleviated the decrease of podocin protein expression and morphological injury of podocyte as screened by Western Blot and electron microscopic analysis. Besides, renal tubular injury was reduced as inspected by light microscopic analysis. TG-n2 and TG could significantly inhibit the apoptosis and activity of caspase-3 in kidney tissues as examined by fluorescence microscopic analysis and reagent. After intervention of TG-n2 and TG, protein levels of cleaved caspase-3, cleaved caspase-8, cleaved caspase-9, Bax, p53 and TNF-R1 in renal issues were significantly decreased compared with ADR group. In contrast, protein level of Bcl-2 was elevated remarkedly., Conclusions: Our data suggested that attenuated TG-n2 may have a similar protective effect with TG in ADR-induced NS in rats by inhibiting activation of apoptosis., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

In previous report, polyvinyl alcohol/liquefied ball-milled chitin (PVA/LBMC) blend films with good antibacterial activity were successfully prepared. To further develop a biodegradable food packaging material, various amounts of nano-silica were introduced in situ by the hydrolysis of Na 2 SiO 3 to give a series of silica-reinforced PVA/LBMC blend films. Their structure, morphology, mechanical and thermal properties, food preservation and degradation behavior in soil were comprehensively characterized. The results showed that when the content of Na 2 SiO 3 was 0.2 wt %, the blend film 4PVA-LBMC-0.2Si displayed the optimized performance. Its tensile strength, and the maximum weight loss rate temperature reached 51 MPa and 307 ℃, respectively, which were significantly improved than those of silica-free film. The preservation tests of cherries showed its good fresh keeping performance. Although the degradation rate of silica-reinforced blend films in the soil was slightly decreased, it remained at a good level of 43 % after 30 days of burial., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Inconsistencies exist regarding the severity of illness caused by different influenza strains. The aim of this study was to compare the clinical outcomes of hospitalized adults and adolescents with influenza-related pneumonia (Flu-p) from type A and type B strains in China., Methods: We retrospectively reviewed data from Flu-p patients in five hospitals in China from January 2013 to May 2019. Multivariate logistic and Cox regression models were used to assess the effects of influenza virus subtypes on clinical outcomes, and to explore the risk factors of 30-day mortality for Flu-p patients., Results: In total, 963 laboratory-confirmed influenza A-related pneumonia (FluA-p) and 386 influenza B-related pneumonia (FluB-p) patients were included. Upon adjustment for confounders, multivariate logistic regression models showed that FluA-p was associated with an increased risk of invasive ventilation (adjusted odds ratio [aOR]: 3.824, 95% confidence interval [CI]: 2.279-6.414; P <  0.001), admittance to intensive care unit (aOR: 1.630, 95% CI: 1.074-2.473, P = 0.022) and 30-day mortality (aOR: 2.427, 95% CI: 1.568-3.756, P <  0.001) compared to FluB-p. Multivariate Cox regression models confirmed that influenza A virus infection (hazard ratio: 2.637, 95% CI: 1.134-6.131, P = 0.024) was an independent predictor for 30-day mortality in Flu-p patients., Conclusions: The severity of illness and clinical outcomes of FluA-p patients are more severe than FluB-p. This highlights the importance of identifying the virus strain during the management of severe influenza.

Background: There are few comparative studies of the clinical outcomes after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). The aim of the study was to compare diabetes- and metabolic disorder-related outcomes following RYGB and SG, based on data for matched participants., Methods: This was a retrospective matched study using data from 2011-2018. Patients with type-2 diabetes undergoing RYGB (n=35) were matched with up to 2 RYGB participants (n=56) regarding age, sex, body mass index, hemoglobin A1c level, medication use, diabetes duration, and blood pressure., Results: All surgeries were performed laparoscopically without complications or malnutrition during 24 months of follow-up. Both surgical procedures achieved excellent diabetes remission and weight loss. RYGB was associated with a significantly higher diabetes medication discontinuation rate 24 months postoperatively (RYGB: 87.5% vs. SG: 68.6%; P<0.05), better reduction in serum cholesterol and low-density lipoprotein-c levels, as well as better diabetes control compared with SG. The incidence of microvascular and macrovascular complications showed no significant difference between two groups., Conclusions: In this matched retrospective study, although RYGB and SG were both excellent surgeries for treating obesity in patients with type-2 diabetes, RYGB was associated with better results compared with SG regarding dyslipidemia remission and metabolic disorder-related medication reduction., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (2020 Annals of Translational Medicine. All rights reserved.)

Triptolide(T9) is a predominant bioactive component extracted from Chinese herb Tripterygium wilfordii Hook F. (TwHF), and has multiple pharmacological activities, such as immunosuppressive and anti-inflammatory activities, et al. However, severe adverse effects and toxicity, particularly nephrotoxicity, limit its clinical application. It has been demonstrated that the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway could alleviate T9-induced nephrocyte damage. The aim of this study was to investigate the potential protective role of triptriolide (T11) against T9-induced nephrocyte apoptosis in vitro and in vivo. Renal injury models were established in human kidney 2 (HK2) cells and BALB/c mice using T9, and the protective effects of T11 were probed in vitro and in vivo, respectively. T9 induced nephrocyte damage in HK2 cells and BALB/c mice by induction of reactive oxygen species (ROS), lactate dehydrogenase (LDH), malondialdehyde (MDA) and glutathione (GSH) and reduction of superoxide dismutase (SOD), which resulted in the apoptosis of nephrocyte and injury of renal function. While, pretreatment of T11 effectively reversed these changes, resulting in the obvious decrease of oxidative stress and renal function parameters, ameliorated nephrocyte apoptosis, improved cell morphology, and higher increase of Nrf2, NAD(P)H: quinine oxidoreductase 1 (NQO1) and heme oxygenase 1 (HO-1) protein levels in vitro and in vivo. Altogether, T11 protected against T9-induced nephrocyte apoptosis possibly via suppressing oxidative stress., (Copyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

InP-InAs-InP multi-shell nanowires (NWs) were grown in the wurtzite (WZ) or zincblende (ZB) crystal phase and their photoluminescence (PL) properties were investigated at low temperature (≈6 K) for different measurement geometries. PL emissions from the NWs were carefully studied in a wide energy range from 0.7 to 1.6 eV. The different features observed in the PL spectra for increasing energies are attributed to four distinct emitting domains of these nano-heterostructures: the InAs island (axially grown), the thin InAs capping shell (radially grown), the crystal-phase quantum disks arising from the coexistence of InP ZB and WZ segments in the same NW, and the InP portions of the NW. These results provide a useful frame for the rational implementation of InP-InAs-InP multi-shell NWs containing various quantum confined domains as polychromatic optically active components in nanodevices for quantum information and communication technologies.

Background: The Tripterygium glycosides (TG) is the main active extractive of Tripterygium wilfordii Hook F and is widely used in clinical practice to treat inflammatory diseases (including inflammatory bowel disease). However, due to its severe toxicity, TG is restricted to the treatment of many diseases. Therefore, it is necessary to study a new method to obtain the attenuated and synergistic extracts from TG., Purpose: Tripterygium glycosides-n2 (TG-n2) was obtained from TG by a new preparation method. In this study, we aimed to investigate the difference in the chemical compositions between TG and TG-n2, further explored its toxicity and therapeutic effects on DSS-induced colitis in mice., Methods: The major chemical compositions of TG and TG-n2 were analyzed by ultra-performance liquid chromatography (UPLC). Subsequently, acute toxicity test was applied to evaluate the toxicity difference between TG and TG-n2. Dextran sulfate sodium (DSS)-induced acute colitis model was used to explore the therapeutic effect of TG and TG-n2 and their potential mechanisms of action., Results: We found that the chemical compositions of TG-n2 is different from TG. The main difference is the ratio of triptriolide (T11) / triptolide (T9). Acute toxicity test proved that TG-n2 was less toxic than TG. Base on this, further studies showed that TG-n2 has a similar therapeutic effect as compared to TG on attenuating the symptoms of colitis, such as diarrhea, bloody stools, body weight loss, colonic atrophy, histopathological changes, inhibiting cytokines secretion and reducing absolute lymph number. In addition, TG and TG-n2 can increase the apoptosis of T lymphocyte in vivo. Further investigated showed that TG and TG-n2 could increase the expressions of Bax and p62 on CD3-positive T cells., Conclusion: This study showed that oral administration of TG-n2 is safer than TG. Moreover, the attenuated TG-n2 has the similar therapeutic effect on treating experimental colitis in mice when compared to TG. Its mechanism may be related to activating the expression of Bax in T cells and inducing T cells autophagy to regulate the survival of T lymphocytes in colitis mice, thus reducing inflammation in colon., (Copyright © 2019. Published by Elsevier GmbH.)

Background/objectives: Drug reaction with eosinophilia and systemic symptoms (DRESS) is rare but potentially fatal in children. Fever and rash, which are salient features of DRESS, may mimic other commonly encountered pediatric conditions. We profiled the DRESS cases in a tertiary children's hospital in Singapore., Methods: The medical records of all pediatric DRESS patients diagnosed from 2006 to 2016. Data on epidemiology, inciting drugs, clinical, pathologic manifestations, and treatment were assessed., Results: Ten patients aged 4-16 years old were diagnosed with DRESS within the 10-year period. Drugs implicated were antibiotics, such as trimethoprim-sulfamethoxazole, and anticonvulsants, such as carbamazepine, phenobarbitone, and levetiracetam. All patients had fever and pruritic exanthems. Desquamation, purpura, and oral mucositis were also observed. Lymphadenopathy, hepatomegaly, and facial edema occurred frequently. There was liver involvement in all cases, but none progressed to liver failure. Seven patients had eosinophilia, and nine had atypical lymphocytosis. Other laboratory abnormalities included low hemoglobin, thrombocytosis, and prolonged coagulation times. All patients received systemic corticosteroids of varying durations and dosages. Systemic steroids were weaned after 19 days to 4 months. Disease resolution, with liver enzyme levels returning to normal, occurred within 28-90 days. One patient developed TSH-receptor-antibody-positive hyperthyroidism 6 months after the onset of DRESS, while another patient developed chronic urticaria 4 months after resolution of DRESS., Conclusion: Early recognition of DRESS is important to ensure that the inciting drug is discontinued, and supportive treatment started expediently. Liver involvement was very common but responded well to systemic steroids., (© 2019 Wiley Periodicals, Inc.)

Triptriolide (T11) is a natural diterpene diepoxide that derived from Chinese traditional herb medicine (TCHM) Tripterygium wilfordii Hook.F (TWHF). From a structural point of view, T11 is very similar to triptolide (T9), one of the most effectively compounds in TWHF that have already been systematically investigated in the past decades. However, the basic functions and medicinal properties of T11 have not yet been well investigated mainly due to its low abundance in its plant organ. The present study aimed to investigate the protective effects of T11 on puromycin aminonucleoside (PAN) induced apoptotic mouse podocytes and the underlying mechanism. The results showed that T11 had no significant toxicity in podocytes in high dosage, and showed prominent protective effects on PAN induced podocytes injury. Further studies indicated that T11 might exert its protective effects by inhibiting of apoptosis and restoring of survival in PAN induced podocytes., (Copyright © 2018 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Alloy design based on single-principal-element systems has approached its limit for performance enhancements. A substantial increase in strength up to gigapascal levels typically causes the premature failure of materials with reduced ductility. Here, we report a strategy to break this trade-off by controllably introducing high-density ductile multicomponent intermetallic nanoparticles (MCINPs) in complex alloy systems. Distinct from the intermetallic-induced embrittlement under conventional wisdom, such MCINP-strengthened alloys exhibit superior strengths of 1.5 gigapascals and ductility as high as 50% in tension at ambient temperature. The plastic instability, a major concern for high-strength materials, can be completely eliminated by generating a distinctive multistage work-hardening behavior, resulting from pronounced dislocation activities and deformation-induced microbands. This MCINP strategy offers a paradigm to develop next-generation materials for structural applications., (Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Objective: Lung adenocarcinoma (LA) is considered as a highly aggressive disease with heterogeneous prognosis. The molecular mechanisms of LA progression remain elusive. Recent studies have shown that dysregulation of microRNAs (miRNAs) is prevalent in LA, playing a significant role in tumor progression. The present work aims to analyze the expression and function of miR-608 in LA., Patients and Methods: Quantitative Real-time polymerase chain reaction (qRT‑PCR) assay and Western blot were performed to detect expressions of miR-608 and migration inhibitory factor (MIF). Luciferase reporter assays were carried out to investigate the regulatory effect of miR-608 on MIF. The cell invasion and the migration capabilities were detected by transwell assay., Results: QRT-PCR indicated that miR-608 expressions in LA tissues were markedly reduced than that of the normal tissues. Moreover, the expression of MIF, a potential target gene of miR-608, was inversely associated with miR-608 expression in LA. Furthermore, miR-608 overexpression could inhibit LA invasion and migration, which was reversed by MIF knockdown., Conclusions: Our study revealed the mechanisms that miR-608 suppressed LA invasion and migration by targeting MIF, suggesting that miR-608/MIF axis could be used as a potential prognostic biomarker and therapeutic target for LA.

Objective: Worldwide, community-acquired pneumonia (CAP) is a common infection that occurs in older adults, who may have pulmonary comorbidities, including chronic obstructive pulmonary disease (COPD). Although there have been clinical studies on the coexistence of CAP with COPD, there remain some controversial findings. This review presents the current status of COPD in CAP patients, including the disease burden, clinical characteristics, risk factors, microbial etiology, and antibiotic treatment., Data Sources: A literature review included full peer-reviewed publications up to January 2018 derived from the PubMed database, using the keywords "community-acquired pneumonia" and "chronic obstructive pulmonary disease"., Study Selection: Papers in English were reviewed, with no restriction on study design., Results: COPD patients who are treated with inhaled corticosteroids are at an increased risk of CAP and have a worse prognosis, but data regarding the increased mortality remains unclear. Although Streptococcus pneumoniae is still regarded as the most common bacteria isolated from patients with CAP and COPD, Pseudomonas aeruginosa is also important, and physicians should pay close attention to the occurrence of antimicrobial resistance, particularly in these two organisms., Conclusions: COPD is a common and important predisposing comorbidity in patients who develop CAP. COPD often aggravates the clinical symptoms of patients with CAP, complicating treatment, but generally does not appear to affect prognosis., Competing Interests: There are no conflicts of interest

Introduction: Cutaneous plasmacytosis (CP) is a rare skin disorder characterized by multiple reddish brown nodules with polyclonal plasma cell proliferation. It has most often been reported to affect the trunk but is also known to affect the face and extremities in adults and is predominantly seen in Asians. The etiology is poorly understood, and there is no consensus on treatment methods., Methods: Five cases diagnosed to have CP were collated from our institution. Their clinicopathologic features and treatment outcomes were reviewed., Results: Four of the 5 patients presented with lesions that affected multiple sites of the body including the trunk, axillae, face, and limbs. The remaining patient had lesions localized to his axillae. The lesions were generally asymptomatic. All patients had hypergammaglobulinaemia but only one had a faint monoclonal band detected on immunofixation. Common findings in the biopsy results for all patients were perivascular plasma cell infiltrates without light chain restriction on kappa/lambda staining, as well as mast cell infiltrates. Partial remission of cutaneous lesions was observed in 3 of the patients, with 2 of them responding well to psoralen and ultraviolet A radiation therapy., Conclusion: CP presents with distinctive clinical features and characteristic histological features including polyclonal perivascular plasma cell infiltrates. The axilla seems to be a frequent and characteristic site of involvement and may be a useful clinical clue to the condition. In the management of patients with CP, it is important to exclude secondary causes of plasmacytic infiltrates. While there are no clearly established treatment modalities for CP, psoralen and ultraviolet A radiation therapy may be a viable option in view of the clinical improvement observed in our patients who received it.

MicroRNA-30e (miR-30e) is downregulated in various tumor types. However, its mechanism in inhibiting tumor growth of breast cancer remains to be elucidated. In this study, we found that miR-30e was significantly downregulated in tumor tissues of breast cancer (BC) patients and cell lines, and overexpression of miR-30e inhibited cell proliferation, migration and invasion. To understand the potential mechanism of miR-30e in inhibiting tumor growth, we showed that miR-30e blocked the activation of AKT and ERK1/2 pathways, and the expression of HIF-1α and VEGF via directly targeting IRS1. Moreover, miR-30e regulates cell proliferation, migration, invasion and increases chemosensitivity of MDA-MB-231 cells to paclitaxel by inhibiting its target IRS1. MiR-30e also inhibited tumor growth and suppressed expression of IRS1, AKT, ERK1/2 and HIF-1α in mouse xenograft tumors. To test the clinical relevance of these results, we used 40 pairs of BC tissues and adjacent normal tissues, analyzed the levels of miR-30e and IRS1 expression in these tissues, and found that miR-30e levels were significantly inversely correlated with IRS1 levels in these BC tissues, suggesting the important implication of our findings in translational application for BC diagnostics and treatment in the future.

The independent control of two magnetic electrodes and spin-coherent transport in magnetic tunnel junctions are strictly required for tunneling magnetoresistance, while junctions with only one ferromagnetic electrode exhibit tunneling anisotropic magnetoresistance dependent on the anisotropic density of states with no room temperature performance so far. Here, we report an alternative approach to obtaining tunneling anisotropic magnetoresistance in α'-FeRh-based junctions driven by the magnetic phase transition of α'-FeRh and resultantly large variation of the density of states in the vicinity of MgO tunneling barrier, referred to as phase transition tunneling anisotropic magnetoresistance. The junctions with only one α'-FeRh magnetic electrode show a magnetoresistance ratio up to 20% at room temperature. Both the polarity and magnitude of the phase transition tunneling anisotropic magnetoresistance can be modulated by interfacial engineering at the α'-FeRh/MgO interface. Besides the fundamental significance, our finding might add a different dimension to magnetic random access memory and antiferromagnet spintronics.Tunneling anisotropic magnetoresistance is promising for next generation memory devices but limited by the low efficiency and functioning temperature. Here the authors achieved 20% tunneling anisotropic magnetoresistance at room temperature in magnetic tunnel junctions with one α'-FeRh magnetic electrode.

Arsenic exposure produces hepatotoxicity. The common mechanism determining its toxicity is the generation of oxidative stress. Oxidative stress induced by arsenic leads to the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. (-)-Epigallocatechin-3-gallate (EGCG) possesses a potent antioxidant capacity and exhibits extensive pharmacological activities. This study aims to evaluate effects of EGCG on arsenic-induced hepatotoxicity and activation of Nrf2 pathway. Plasma activities of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase were measured; Histological analyses were conducted to observe morphological changes; Biochemical indexes such as oxidative stress (Catalase (CAT), malonyldialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), reactive oxygen species (ROS)), Nrf2 signaling related genes ( Nrf2, Nqo1, and Ho-1 ) were assessed. The results showed that EGCG inhibited arsenic-induced hepatic pathological damage, liver ROS level and MDA level. Arsenic decreases the antioxidant enzymes SOD, GPX, and CAT activity and the decrease was inhibited by treatment of EGCG. Furthermore, EGCG attenuated the retention of arsenic in liver tissues and improved the expressions of Nrf2 signaling related genes ( Nrf2, Nqo1, and Ho-1 ). These findings provide evidences that EGCG may be useful for reducing hepatotoxicity associated with oxidative stress by the activation of Nrf2 signaling pathway. Our findings suggest a possible mechanism of antioxidant EGCG in preventing hepatotoxicity, which implicate that EGCG may be a potential treatment for arsenicosis therapy., Competing Interests: CONFLICTS OF INTEREST The authors state no conflicts of interest.

Here, we report that it's feasible for imaging gastric adenocarcinoma mice model with prostate-specific membrane antigen (PSMA) targeting imaging agents, which could potentially provide an alternate and readily translational tool for managing gastric adenocarcinoma. DKFZ-PSMA-617, a PSMA targeting ligand reported recently, was chosen to be radio-labeled with nuclide 64 Cu. 64 Cu-PSMA-617 was radio-synthesized in high radio-chemical yield and specific activity up to 19.3 GBq/µmol. It showed good stability in vitro . The specificity of 64 Cu-PSMA-617 was confirmed by cell uptake experiments in PSMA (+) LNCaP cell and PSMA (-) PC-3 and gastric adenocarcinoma BGC-823 cells. Micro-PET imaging in BGC-823 and PC-3 xenografts nude mice was evaluated ( n = 4). And the tumors were visualized and better tumor-to-background achieved till 24 h. Co-administration of N- [[[(1S)-1-Carboxy-3-methylbutyl]amino]-carbonyl]-L-glutamic acid (ZJ-43) can substantially block the uptake in those tumors. Dissected tumor tissues were analyzed by auto-radiography and immunohistochemistry, and these results confirmed the PSMA expression in neo-vasculature which explained the target molecular imaging of 64 Cu-PSMA-617. All those results suggested 64 Cu-PSMA-617 may serve as a novel radio-tracer for tumor imaging more than prostate cancer., Competing Interests: CONFLICTS OF INTEREST The authors declare no competing financial interests.

Background: The hematopoietic system is especially sensitive to total body irradiation (TBI), and myelosuppression is one of the major effects of TBI. Astaxanthin (ATX) is a powerful natural anti-oxidant with low toxicity. In this study, the effect of ATX on hematopoietic system injury after TBI was investigated., Methods: Flow cytometry was used to detect the proportion of hematopoietic progenitor cells (HPCs) and hematopoietic stem cells (HSCs), the level of intracellular reactive oxygen species (ROS), expression of cytochrome C, cell apoptosis, and NRF2-related proteins. Immunofluorescence staining was used to detect Nrf2 translocation. Western blot analysis was used to evaluate the expression of apoptotic-related proteins. Enzymatic activities assay kits were used to analyze SOD2, CAT, and GPX1 activities., Results: Compared with the TBI group, ATX can improve radiation-induced skewed differentiation of peripheral blood cells and accelerate hematopoietic self-renewal and regeneration. The radio-protective effect of ATX is probably attributable to the scavenging of ROS and the reduction of cell apoptosis. These changes were associated with increased activation of Nrf2 and downstream anti-oxidative proteins, and regulation of apoptotic-related proteins., Conclusions: This study suggests that ATX could be used as a potent therapeutic agent to protect the hematopoietic system against TBI-induced bone marrow suppression.

This study aims to evaluate the effect of naloxone on intravenous fentanyl patient-controlled analgesia after laparoscopic cholecystectomy under total intravenous anesthesia.A total of 90 patients, who underwent intravenous fentanyl patient-controlled analgesia after laparoscopic cholecystectomy under total intravenous anesthesia, were included into this study. All patients were randomly divided into 3 groups (each group, n=30): naloxone group (naloxone+fentanyl), tropisetron group (tropisetron+fentanyl), and fentanyl group (fentanyl). Patients in each group were given a corresponding dose of naloxone. Postoperative analgesia effect and the incidence of side effects such as nausea and vomiting were observed.Small doses of naloxone or tropisetron combined with fentanyl used for intravenous patient-controlled analgesia can significantly reduce the incidence of nausea and vomiting. Six hours after surgery, visual analogue scale (VAS) scores were significantly lower in patients that underwent intravenous patient-controlled analgesia using low-dose naloxone combined with fentanyl compared with patients who received fentanyl alone; however, the postoperative analgesic effect of tropisetron was not observed. Compared with the combination of tropisetron and fentanyl, low-dose naloxone combined with fentanyl can obviously reduce the incidence of nausea and vomiting in patients who underwent intravenous patient-controlled analgesia after laparoscopic cholecystectomy, and enhance the analgesic effect of fentanyl 6 hours after surgery.Low-dose naloxone can reduce the incidence of nausea and vomiting in patients who underwent laparoscopic cholecystectomy under total intravenous anesthesia, and exhibits a certain synergic analgesic effect., Competing Interests: The authors have no funding and conflicts of interest to disclose.

Introduction: Acne vulgaris commonly affects adolescents. But recent reports suggest a rising prevalence of post-adolescence acne. While there are few reports on post-adolescence acne, there are even fewer reports comparing adolescence acne and post-adolescence., Methods: Epidemiological data of adolescence (<25 years) and post-adolescence (≥25 years) acne patients diagnosed between 2004 and 2013 in a tertiary dermatology referral centre was analysed. From the pool of patients seen in 2010, 80 adolescence and 84 post-adolescence acne patients' epidemiological characteristics and treatment responses were analysed., Results: During the 10-year study period, there was an increase in the number and proportion of acne cases. In 2004, 4447 (5.77%) of all new diagnoses made were of acne vulgaris. The proportion rose to 5723 (8.13%) in 2013. There were consistently more female than male acne patients. The proportion of post-adolescent cases remained constant at about 30% of all acne patients seen. Mean age of acne vulgaris patients decreased from 23.1 years in 2004 to 22.6 years in 2013. In the subgroup analysis, there were more males than females with adolescence acne (61.3% vs. 38.8%, P < 0.01) and more females with post-adolescence acne (69.0% vs. 31.0%, P < 0.01). Thirty-four (40.5%) post-adolescence acne patients had acne from adolescence persisting into adulthood. Comedonal acne was more prevalent in the adolescence acne patients (58.8% vs. 40.5%, P = 0.019), whereas cystic acne was more prevalent in post-adolescence patients (18.1% vs. 7.5%, P = 0.044). Systemic retinoids were more often used for treatment in the adolescence acne patients than post-adolescence acne patients (23.8% vs. 10.7%, P = 0.027)., Conclusion: Acne predominantly affects adolescents but post-adolescence acne is not uncommon. For post-adolescence acne, females predominate over males. Inflammatory and cystic acne tends to be more predominant in post-adolescence acne patients, whereas comedonal acne is more often seen in adolescence acne patients., (© 2016 European Academy of Dermatology and Venereology.)

Ge-Sb-Te alloys have been widely used in optical/electrical memory storage. Because of the extremely fast crystalline-amorphous transition, they are also expected to play a vital role in next generation nonvolatile microelectronic memory devices. However, the distribution and structural properties of vacancies have been one of the key issues in determining the speed of melting (or amorphization), phase-stability, and heat-dissipation of rock-salt GeSbTe, which is crucial for its technological breakthrough in memory devices. Using spherical aberration-aberration corrected scanning transmission electron microscopy and atomic scale energy-dispersive X-ray mapping, we observe a new rock-salt structure with high-degree vacancy ordering (or layered-like ordering) at an elevated temperature, which is a result of phase transition from the rock-salt phase with randomly distributed vacancies. First-principles calculations reveal that the phase transition is an energetically favored process. Moreover, molecular dynamics studies suggest that the melting of the cubic rock-salt phases is initiated at the vacancies, which propagate to nearby regions. The observation of multi-rock-salt phases suggests another route for multi-level data storage using GeSbTe.