Pterostilbene upregulates MICA/B via the PI3K/AKT signaling pathway to enhance the capability of natural killer cells to kill cervical cancer cells.

Natural killer (NK) cells are triggered by the innate immune response in the tumor microenvironment. The extensive set of stimulating and inhibiting receptors mediates the target recognition of NK cells, and controls the strength of the effector reaction countering specific targeted cells. Yet, lacking major MHC (histocompatibility complex) MICA/B class I chain-related proteins on the membrane of tumor cells results in the failure of NK cell recognition and ability to resist NK cell destruction. Searching databases and molecular docking suggested that in cervical cancer, pterostilbene (3,5-dimethoxy-40-hydroxystilbene; PTS) in Vaccinium corymbosum extract could constrain PI3K/AKT signaling and improving the MICA/B expression. In flow cytometry, MTT assay, viability/cytotoxicity assay, and colony development assays, PTS reduced the development of cervical cancer cells and increased apoptosis. The quantitative real-time PCR (qRT-PCR) and a Western blot indicate that PTS controlled the cytolytic action of NK cells in tumor cells via increasing the MICA/B expression, thus modifying the anti-tumor immune response in cervical cancer.

Construction of SLC16A1/3 Targeted Gallic Acid-Iron-Embelin Nanoparticles for Regulating Glycolysis and Redox Pathways in Cervical Cancer.

SLC16A1 and SLC16A3 (SLC16A1/3) are highly expressed in cervical cancers and associated with the malignant biological behavior of cancer. SLC16A1/3 is the critical hub for regulating the internal and external environment, glycolysis, and redox homeostasis in cervical cancer cells. Inhibiting SLC16A1/3 provides a new thought to eliminate cervical cancer effectively. There are few reports on effective treatment strategies to eliminate cervical cancer by simultaneously targeting SLC16A1/3. GEO database analysis and quantitative reverse transcription polymerase chain reaction experiment were used to confirm the high expression of SLC16A1/3. The potential inhibitor of SLC16A1/3 was screened from Siwu Decoction by using network pharmacology and molecular docking technology. The mRNA levels and protein levels of SLC16A1/3 in SiHa and HeLa cells treated by Embelin (EMB) were clarified, respectively. Furthermore, the Gallic acid-iron (GA-Fe) drug delivery system was used to improve its anti-cancer performance. Compared with normal cervical cells, SLC16A1/3 mRNA was over-expressed in SiHa and HeLa cells. Through the analysis of Siwu Decoction, a simultaneously targeted SLC16A1/3 inhibitor EMB was discovered. It was found for the first time that EMB promoted lactic acid accumulation and further induced redox dyshomeostasis and glycolysis disorder by simultaneously inhibiting SLC16A1/3. The gallic acid-iron-Embelin (GA-Fe@EMB) drug delivery system delivered EMB, which had a synergistic anti-cervical cancer effect. Under the irradiation of a near-infrared laser, the GA-Fe@EMB could elevate the temperature of the tumor area effectively. Subsequently, EMB was released and mediated the lactic acid accumulation and the GA-Fe nanoparticle synergistic Fenton reaction to promote ROS accumulation, thereby increasing the lethality of the nanoparticles on cervical cancer cells. GA-Fe@EMB can target cervical cancer marker SLC16A1/3 to regulate glycolysis and redox pathways, synergistically with photothermal therapy, which provides a new avenue for the synergistic treatment of malignant cervical cancer.

Identification of risk factors of acute coronary syndrome in young patients between 18-40 years of age at a teaching hospital.

OBJECTIVES: To identify the risk factors in acute coronary syndrome. METHODS: It was a case series study, conducted in coronary care unit of Jinnah Hospital, Lahore from January to December 2018. Convenient sampling was used for patients' selection. The serum cardiac enzymes level was measured, and serial ECG was done at admission and repeated if required. Blood samples were collected after an overnight fast of 14 hours and tests were done for total cholesterol and HDL cholesterol. RESULTS: Out of 300 patients of acute coronary syndrome, 100 (33.33%) were female and 200 (66.67%) were males. Majority of patients 180 (60%) belonged to age group of 25-40 years. Out of 300 patients 94 (31.33%) had diabetes mellitus, while 139 (46.3%) were suffering from hypertension. Out of 290 patients 95 (32.7%) had family history of coronary artery disease. Out of 298 patients 125 (41.9%) were smokers. CONCLUSION: Acute coronary syndrome in age group of 18- 40 Years showed a male predominance with major modifiable risk factors; Hypertension followed by Diabetes mellitus, smoking and Dyslipidemia. Positive family history a non-modifiable risk factor in patients of ACS was also a common finding.

Impact of educational intervention on hypertension management by primary care physician: A randomized control trial.

Objective: The current study aimed to observe hypertension educational intervention's effect on general physicians (GPs) to improve blood pressure control and patient outcomes indirectly. Methods: This randomized control trial includes 42 GPs divided into 2 groups. GPs in group 1 receive face-to-face education with structured educational material on hypertension management strategies by a senior cardiologist. GPs in group 2 receive the print version of education material. The data was collected from six major cities in Pakistan. GPs with at least three years of experience in the broad primary care disciplines, with ages above 18 years, were included in the study. Results: A total of 42 physicians (21 from each group) completed questionnaires, while out of 420 hypertension patients, 105 newly diagnosed and already diagnosed patients enrolled under physicians of both groups. The educational material did just as well at informing clinicians as the face-to-face group intervention did and both the interventions had a significant effect on knowledge and BP control. Conclusion: After the 3-month follow-up, both interventions, including face-to-face and educational approaches, demonstrated significant effectiveness in improving knowledge and blood pressure control. Innovation: The study shows that hypertension educational intervention's effect on general physicians indirectly improves blood pressure control and patient outcomes. And emphasize for developing a hypertension educational program targeted at general physicians.

Recent Advancements in Metal and Non-Metal Mixed-Doped Carbon Quantum Dots: Synthesis and Emerging Potential Applications.

In nanotechnology, the synthesis of carbon quantum dots (CQDs) by mixed doping with metals and non-metals has emerged as an appealing path of investigation. This review offers comprehensive insights into the synthesis, properties, and emerging applications of mixed-doped CQDs, underlining their potential for revolutionary advancements in chemical sensing, biosensing, bioimaging, and, thereby, contributing to advancements in diagnostics, therapeutics, and the under standing of complex biological processes. This synergistic combination enhances their sensitivity and selectivity towards specific chemical analytes. The resulting CQDs exhibit remarkable fluorescence properties that can be involved in precise chemical sensing applications. These metal-modified CQDs show their ability in the selective and sensitive detection from Hg to Fe and Mn ions. By influencing their exceptional fluorescence properties, they enable precise detection and monitoring of biomolecules, such as uric acid, cholesterol, and many antibiotics. Moreover, when it comes to bioimaging, these doped CQDs show unique behavior towards detecting cell lines. Their ability to emit light across a wide spectrum enables high-resolution imaging with minimal background noise. We uncover their potential in visualizing different cancer cell lines, offering valuable insights into cancer research and diagnostics. In conclusion, the synthesis of mixed-doped CQDs opens the way for revolutionary advancements in chemical sensing, biosensing, and bioimaging. As we investigate deeper into this field, we unlock new possibilities for diagnostics, therapeutics, and understanding complex biological processes.

The influence of big data analytic capabilities building and education on business model innovation.

As organizations are benefiting from investments in big data analytics capabilities building and education, our study has analyzed the impact of big data analytics capabilities building and education on business model innovation. It has also assessed technological orientation and employee creativity as mediating and moderating variables. Questionnaire data from 499 managers at enterprises in Jiangsu, China have been analyzed using Structural Equation Modeling (SEM) in SmartPLS. Big data analytics capabilities building and education strengthen technological orientation and increase business model innovation. Technology orientation increases business model innovation and plays a mediating role. Employee creativity also boosts innovation. These findings show that business managers should adopt and promote a technological orientation. They should hire and train employees with big data education and training. Organizations can try to select and support employees who show creativity.

A Potential Driver of Disseminated Intravascular Coagulation in Heat Stroke Mice: Neutrophil Extracellular Traps.

AIMS: Disseminated intravascular coagulation (DIC) is a common complication of heat stroke (HS) patients, and it is one of the important reasons leading to multiple organ failure and even death. The association between neutrophil extracellular traps (NETs) and DIC is unclear in HS mice. METHODS AND RESULTS: Here, HS was induced by the combination of hyperthermia (HT) and lipopolysaccharide (LPS). The DIC was evaluated by measuring prothrombin time (PT), D-dimer, thrombomodulin (TM), fibrinogen (FIB), and platelet (PLT). The expression of citrullinated-histone (CitH3) was analyzed by Western blotting. The formation of NETs was observed by immunofluorescence microscopy. The risk of HS-induced DIC was increased when HT was combined with LPS. The markers of NETs were significantly higher than those in the control group, and the NETs derived from HS promoted the development of DIC. DNase I improved coagulation dysfunction via the clearance of NETs caused by neutrophil aggregation. CONCLUSIONS: Degradation of NETs reduced the risk of developing DIC, and thus the survival rate of mice was improved. These results indicate that NETs may hold potential alternative therapeutic strategies for the treatment of DIC in HS patients.

Serum high sensitivity C-reactive protein levels and the severity of coronary atherosclerosis assessed by angiographic gensini score.

OBJECTIVE: To assess the relationship between plasma high sensitivity C-reactive protein levels with severity of coronary atherosclerosis. MATERIALS AND METHODS: The study included 80 patients subjected to coronary angiography. The extent of Coronary Artery Disease (CAD) was assessed using Gensini score. Patients were divided into three risk groups according to hs-CRP levels (< 1 mg/L--as low risk, 1-3 mg/L--as average risk and >3 mg/L--as high risk). Mean Angiographic Gensini scores were compared among the risk groups. Correlation between serum hs-CRP levels and angiographic Gensini scores was also assessed. RESULTS: The 26 (32.5%) patients belonging to hs-CRP low-risk group had a mean angiographic Gensini score of 11.8 +/- 5.8, 18 (22.5%) belonging to moderate-risk group had a mean score of 28.9 +/- 7.9 and 36 (45%) belonging to high- risk group had a mean score of 78.7 +/- 41.0. By applying ANOVA the mean angiographic Gensini scores showed increasing trend from lower to higher hs-CRP risk groups (p < 0.001). Serum hs-CRP levels showed significant correlation with respective angiographic Gensini scores by Pearson's correlation (p < 0.001). CONCLUSION: Serum hs-CRP levels show significant correlation with the severity of Coronary Artery Disease as assessed by angiographic Gensini score.

Does Polychronicity Undermine Procrastination Behavior Through ICTs? Insights From Multi-Level Modeling.

Information and communication technologies (ICTs) are widely used in developing nations as a dynamic solution for socio-economic development. Pakistan has seen a rapid increase in the use of ICTs during the previous decade. The purpose of this study is to examine how polychronicity affects procrastination behavior when it is influenced by ICTs. According to this study, individuals are described as a dynamic and destructive kind of self-regulation failure in ICTs. Procrastination is a behavior that prevents emerging economies from growing from developing countries. We researched the group-level polychronicity influence of the individual behavior and the mechanism of procrastination from a team-level perspective of worker behavior. This study data collected 231 workers from 76 groups working in ICTs in Pakistan. The results revealed that the group polychronicity and the behavior of group members were positively linked by taking the work overload as a mediator. Moreover, group cohesiveness moderates the role between polychronicity and work overload diminishing the mediation procession between-group polychronicity and individual procrastination. The practical importance of this study is to understand the causes of procrastination, and how to decrease this obstacle to a fairer workplace. It also helps to decide the professional route that is most suited to personality characteristics.

Examining How Ambidextrous Leadership Relates to Affective Commitment and Workplace Deviance Behavior of Employees: The Moderating Role of Supervisor-Subordinate Exchange Guanxi.

How to regulate employee conduct and engage them in high performance works actively and continuously has always been the important topic for organizations. Based on affective events theory and social exchange theory, a moderated mediating model was constructed with the affective commitment as mediator and the supervisor-subordinate exchange guanxi as moderator. Regression analyses and conditional indirect effects were tested by SPSS and PROCESS with 374 matched supervisor-subordinate pairs. The paper explores the moderated mechanism of supervisor-subordinate guanxi to the chain of "ambidextrous leadership-employee's affective commitment-workplace deviance behavior." The results showed that the affective commitment mediated the effect between ambidextrous leadership and employees' workplace deviance behavior, and supervisor-subordinate exchange guanxi moderated the relationship between ambidextrous leadership and employees' workplace deviance behavior but also moderated the mediating effect of affective commitment. The results have significances to improve human resource management practices and reduce the workplace deviance behavior of employees.

In-hospital outcome of acute myocardial infarction in correlation with 'thrombolysis in myocardial infarction' risk score.

BACKGROUND: Effective risk stratification is integral to management of acute coronary syndromes (ACS). The Thrombolysis in Myocardial Infarction (TIMI) risk score for ST-segment elevation myocardial infarction (STEMI) is a simple integer score based on 8 high-risk parameters that can be used at the bedside for risk stratification of patients at presentation with STEMI. OBJECTIVES: To evaluate the prognostic significance of TIMI risk score in a local population group of acute STEMI. METHODS: The study included 160 cases of STEMI eligible for thrombolysis. TIMI risk score was calculated for each case at the time of presentation and were then followed during their hospital stay for the occurrence of electrical and mechanical complications as well as mortality. The patients were divided into three risk groups, namely 'low-risk', 'moderate-risk' and 'high-risk' based on their TIMI scores (0-4 low-risk, 5-8 moderate-risk, 9-14 high risk). The frequencies of complications and deaths were compared among the three risk groups. RESULTS: Post MI arrhythmias were noted in 2.2%, 16% and 50%; cardiogenic shock in 6.7%, 16% and 60%; pulmonary edema in 6.7%, 20% and 80%; mechanical complications of MI in 0%, 8% and 30%; death in 4.4%, 8%, and 60% of patients belonging to low-risk, moderate-risk and high-risk groups respectively. Frequency of complications and death correlated well with TIMI risk score (p = 0.001). CONCLUSION: TIMI risk score correlates well with the frequency of electrical or mechanical complications and death after STEMI.

When Employees are Emotionally Exhausted Due to Abusive Supervision. A Conservation-of-Resources Perspective.

This study represents an important step towards understanding why supervisors behave abusively towards their subordinates. Building on the conservation of resources theory, this study investigates the impact of abusive supervision on counterproductive work behaviors (CWBs) from a stress perspective. Furthermore, job demands play a significant moderating effect, and emotional exhaustion has a mediating effect on the relationship between abusive supervision and CWBs. A time-lagged design was utilized to collect the data and a total of 350 supervisors-subordinates' dyads are collected from Chinese manufacturing firms. The findings indicate that subordinates' emotional exhaustion mediates the relationship between abusive supervision and CWBs only when subordinates are involved in a high frequency of job demands. Additionally, emotional exhaustion and abusive supervision were significantly moderated by job demands. However, the extant literature has provided that abusive supervision has detrimental effects on employees work behavior. The findings of this study provide new empirical and theoretical insights into the stress perspectives. Finally, implications for managers and related theories are discussed, along with the boundaries and future opportunities of this study.

Identification and analysis of driving factors of CO2 emissions from economic growth in Pakistan.

This study applied the logarithmic mean Divisia index (LMDI) model to identify and discuss the main drivers of Pakistan's CO2 emissions over the period 1990-2016. The study examined the effects of five factors based on Pakistan's three main economic sectors while considering the 11 types of fuels consumed in that country. The results showed that the energy structure effect is the greatest driving force of CO2 emissions in this country, followed by scale effect and economic structure effect. Energy intensity is the main contributor to reducing Pakistan's carbon emissions throughout the study period. A comparative review at the sectoral level shows that the industrial sector for which coal is the main source of energy supply is the one that contributes the most to CO2 emissions in Pakistan. Alongside this sector is the tertiary sector, where the transport sub-sector imposes rules of conduct based on a growing Pakistani population. Meanwhile, deforestation would be the main cause of CO2 emissions from the agricultural sector in Pakistan, as energy consumption in this sector remains very low. Improving energy efficiency through the intensification of clean energy is urgently needed if Pakistan's environmental goals are to be achieved.

Correlation of severity of ST segment elevation in acute inferior wall myocardial infarction with the proximity of right coronary artery disease.

BACKGROUND: A number of researchers have used different electrocardiographical criteria to predict the culprit vessel in acute interior wall myocardial infarction (MI) cases. Therefore, the determination of infarct related artery in AMI is extremely important with regard to prediction of potential complications, furthermole, predicting the probable site of occlusion within RCA is worthwhile because proximal occlusions are likely to cause greater myocardial damage and an early invasive strategy may be planned in such cases. Our study aimed at evaluating the ECG criteria to predict the proximity of lesion in the right coronary artery (RCA) in acute inferior wall MI cases. The Objectives were to predict the presence of a proximal lesion in right coronary artery by severity of ST segment elevation in inferior ECG leads. This cross sectional study carried out at the department of cardiology and cardiac catheterization at Jiinnah Hospital, Lahore from April 2008 to September 2008. METHODS: A total of 60 patients who suffered from inferior wall MI were included in the study who underwent coronary angiography in the first week. The ECGs of these patients were then compared with the angiographic findings to correlate the proximity of culprit lesion in RCA with the degree of ST segment elevation in inferior limb leads. RESULTS: Out of 60 patients, 29 (48.4%) had the culprit lesion in proximal, 23 (38.5%) in mid and 8 (13.4%) in distal RCA. Patients with proximal RCA disease showed a mean ST segment elevation of 12.55 +/- 1.38 mm, with mid RCA disease 8.39 +/- 0.89 mm and with distal RCA disease 6.0 +/- 0.54 mm. CONCLUSION: This study demonstrated that the severity of ST segment elevation was correlated with proximity of RCA lesion.

Parachute-Like Mitral Valve Tuberculoma: A Rare Presentation.

There have been anecdotal reports of tuberculous cardiac involvement, mainly in cases of military tuberculosis or immune deficient individuals. The spectrum of clinical presentations of tuberculous cardiac involvements includes incidental detection of single and multiple well-circumscribed tuberculomas, symptomatic obstructive lesions, AV conduction abnormalities, and even sudden death. We present a case of cardiac tuberculoma in an immune-competent person who presented with worsening dyspnea. The unique morphology of this mass posed an imaging challenge that required 4-dimensional (4D) echocardiography and cardiac magnetic resonance (CMR) detail to differentiate the mass from an anterior mitral leaflet (AML) aneurysm. Histological examination after surgical resection confirmed its tuberculous etiology.