The mutual interplay between NTRK fusion genes and human papillomavirus infection in cervical cancer progression (Review).

Cervical cancer is a significant global health concern, with a substantial portion of cases attributed to human papillomavirus (HPV) infection. Recent advancements in molecular profiling have identified distinct subtypes of cervical cancer based on their genomic alterations. One such subgroup is neurotrophic tropomyosin receptor kinase (NTRK) fusion-positive cervical cancers, characterized by gene fusions involving the NTRK genes. Although both NTRK fusion genes and HPV infections are independently recognized as significant risk factors in cervical cancer, their interplay and mutual effects on cancer progression are not yet fully understood. The present review is the first of its kind to explore the potential interplay between NTRK fusion genes and HPV infections. It surveys in detail how their combined effect can influence the signaling pathways during cervical cancer development and progression. Moreover, the present study discussed the clinical features, histopathological examinations, treatment procedures and follow-up outcomes of NTRK-fusion gene-positive cervical cancer. The present review may help in the understanding of the management and treatment of such rare, lethal and resistant cervical cancers.

CAR-NK Cell Therapy: A Transformative Approach to Overcoming Oncological Challenges.

The use of chimeric antigen receptor (CAR) in natural killer (NK) cells for cancer therapy is gaining momentum, marking a significant shift in cancer treatment. This review aims to explore the potential of CAR-NK cell therapy in cancer immunotherapy, providing a fresh perspective. It discusses the innovative approaches in CAR-NK cell design and engineering, particularly targeting refractory or recurrent cancers. By comparing CAR-NK cells with traditional therapies, the review highlights their unique ability to tackle tumor heterogeneity and immune system suppression. Additionally, it explains how novel cytokines and receptors can enhance CAR-NK cell efficacy, specificity, and functionality. This review underscores the advantages of CAR-NK cells, including reduced toxicity, lower cost, and broader accessibility compared to CAR-T cells, along with their potential in treating both blood cancers and solid tumors.

Investigating the causal impact of different types of physical activity on psychiatric disorders across life stages: A Mendelian randomization study.

BACKGROUND: Psychiatric disorders, including attention-deficit hyperactivity disorder (ADHD), depression, anxiety disorders, and dementia, manifest differently across life stages, impacting cognitive, emotional, and behavioral health. Understanding the causal relationships between various types of physical activity and these disorders is crucial for developing targeted interventions. METHODS: The summary level data from GWAS was utilized to conduct a two-sample Mendelian Randomization (MR) analysis. We assessed the potential causal relationships between different types of physical activity including light do it yourself (DIY) activities, heavy DIY activities, strenuous sports, and aerobic exercises/other exercises and the prevalence of psychiatric disorders (ADHD, depression, anxiety disorders, and dementia) across different life stages. RESULTS: The MR analysis showed no causal relationship between light DIY activities and any of the psychiatric disorders studied. Heavy DIY activities showed a significant negative association with anxiety disorders but no links with ADHD, depression, or dementia. Strenuous sports did not demonstrate any causal relationship with the psychiatric disorders examined. Aerobic exercises were notably correlated with a reduced risk of depression, although no significant associations were found with ADHD, anxiety disorders, or dementia. CONCLUSIONS: The findings indicate that heavy DIY activities might contribute to reducing anxiety disorders, while aerobic exercises potentially lower the risk of depression. These results emphasize the potential benefits of promoting specific types of physical activity to improve mental health outcomes across different life stages. Future research could further investigate the mechanisms underlying these relationships and consider diverse populations and objective measures of physical activity.

Metal pollution in the topsoil of lands adjacent to Sahiwal Coal Fired Power Plant (SCFPP) in Sahiwal, Pakistan.

Coal fly ash from a coal fired power plant is a significant anthropogenic source of various heavy metals in surrounding soils. In this study, heavy metal contamination in topsoil around Sahiwal coal fired power plant (SCFPP) was investigated. Within distance of 0-10, 11-20, 21-30 and 31-40 km of SCFPP, total 56 soil samples were taken, 14 replicate from each distance along with a background subsurface soil sample beyond 60 km. Soil samples were subjected to heavy metals analysis including Fe, Cu and Pb by Atomic Absorption Spectrophotometer (AAS). Composite samples for each distance were analyzed for Al, As, Ba, Cd, Co, Cr, Mn, Mo, Ni, Se, Sr, Zn by Inductively Coupled Plasma (ICP). Pollution indices of exposed soil including Enrichment Factor (EF), Contamination Factor (CF), Geoaccumulation Index (Igeo), and Pollution Load Index (PLI) were calculated. Ecological risk index ([Formula: see text]) of individual metals and the Potential Ecological Risk Index (PERI) for all metals were determined. Soil samples within 40 km of SCFPP were significantly polluted with Pb (mean 2.81 ppm), Cu (mean 0.93 ppm), and Fe (mean 7.93 ppm) compared to their background values (Pb 0.45, Cu 0.3, and Fe 4.9 ppm). Some individual replicates were highly contaminated where Pb, Fe, and Cu values were as high as 6.10, 35.4 and 2.51 ppm respectively. PLI, Igeo, CF, and EF for metals classified the soil around CFPP as "moderate to high degree of pollution", "uncontaminated to moderately contaminated", "moderate to very high contamination", and "moderate to significant enrichment" respectively with average values for Cu as 2.75, 0.82, 3.09, 4.01; Pb 4.79, 1.56, 6.16, 7.76, and for Fe as 1.20, 0.40, 1.62, 3.35 respectively. Average Ecological Risk Index ([Formula: see text]) of each metal and Potential Ecological Risk Index (PERI) for all metals classified the soils as "low risk soils" in all distances. However, ([Formula: see text]) of Pb at a number of sites in all distances have shown "moderate risk". The linear correlation of physico-chemical parameter (EC, pH, Saturation %) and metals have recorded several differential correlations, however, their collective impact on Pb in 0-10 km, has recorded statistically significant correlation (p-value 0.01). This mix of correlations indicates complex interplay of many factors influencing metal concentrations at different sampling sites. The concentration of As, Cr, Co, Cd, and Zn was found within satisfactory limits and lower than in many parts of the world. Although the topsoil around SCFPP is largely recorded at low risk, for complete assessment of its ecological health, further research considering comprehensive environmental parameters, all important trace metals and variety of input pathways is suggested.

Mechanical ventilation in acute myocardial infarction: Outcomes from a prospective audit at a cardiovascular hospital in Pakistan.

BACKGROUND: This clinical audit aims to evaluate the clinical data regarding the management and outcomes of acute myocardial infarction (AMI) patients requiring mechanical ventilator (MV) support, along with identifying factors associated with prolonged MV support and 180-day mortality. MATERIALS AND METHODS: In this study, we audited clinical data regarding management, in-hospital and short-term outcomes of adult patients with AMI required MV support. Patients with prolonged MV duration (>24h) and/or 180-day mortality were compared with their counterparts, and associated factors were identified. The binary logistic and Cox regression analyses were performed to determine the predictors of prolonged MV duration and 180-day mortality. RESULTS: In a sample of 312 patients, 72.8% were male, and the mean age was 60.3±11.5 years. The median MV duration was 24 [24-48] hours, with 48.7% prolonged MV duration. The admission albumin level was found to be the independent predictor of prolonged MV duration with an adjusted OR of 0.42 [0.22-0.82]. Overall 7.4% were re-intubated, 6.7% needed renal replacement therapy, 17.6% required intra-aortic balloon pump (IABP) placement, and 16.7% required temporary pacemaker placement. The survival rate was 80.4% at the time of hospital discharge, 74.7% at 30-day, 71.2% at 90-day, and 68.6% at 180-day follow-up. Age, prolonged MV duration, and ejection fraction were found to be the independent predictors of cumulative 180-day mortality with adjusted HR of 1.04 [1.02-1.07], 1.02 [1.01-1.03], and 0.95 [0.92-0.98], respectively. CONCLUSIONS: Prolonged ventilator duration has significant prognostic implications; hence, tailored early recognition of high-risk patients needing more aggressive care can improve the outcomes.

Molecular identification and differential proteomics of drug resistant Salmonella Typhi.

This study aimed to elucidate differentially expressed proteins in drug resistant Salmonella Typhi. Among 100 samples, S. typhi were identified in 43 samples. In drug susceptibility profile, 95.3% (41/43), 80% (35/43) and 70% (30/43) resistances were observed against Nalidixic acid, Ampicillin, and Chloramphenicol respectively. No resistance was observed against Imipenum and Azithromycin while only 11% (5/43) isolates were found resistant to Ceftriaxone. Mass spectrometric differential analysis resulted in 23 up-regulated proteins in drug resistant isolates. Proteins found up-regulated are involved in virulence (vipB, galU, tufA, and lpp1), translation (rpsF, rpsG, rplJ, and rplR), antibiotic resistance (zwf, phoP, and ompX), cell metabolism (metK, ftsZ, pepD, and secB), stress response (ridA, rbfA, and dps), housekeeping (gapA and eno) and hypothetical proteins including ydfZ, t1802, and yajQ. These proteins are of diverse nature and functions but highly interconnected. Further characterization may be helpful for elucidation of new biomarker proteins and therapeutic drug targets.

Immunoaffinity-based mass spectrometric characterization of immunoreactive proteins of Salmonella Typhi.

Salmonella Typhi, a human-restricted Gram negative enterobacteriaceae, is the causative agent of typhoid fever in human being. The available serodiagnostic tools for the diagnosis of typhoid fever lack sensitivity and/or specificity. This study aimed to identify the immunoreactive proteins of S. Typhi that could help to develop improved diagnostic tools. Here, we performed immunoaffinity-based proteomic approach that uses charged columns to retrieve IgG and IgM antibodies from the plasma of typhoid patients followed by capture of S. Typhi proteins. These proteins were then characterized by mass spectrometry and bioinformatics tools. Using this approach, we identified 28 immunoreactive proteins of S. Typhi, in which 14 proteins were captured by IgG charged column and 4 proteins were captured by IgM column. We also identified 10 proteins (hlyE, rfbH, dapD, argI, glyA, pflB, trxB, groEL, tufA and pepD) captured by both columns. The prediction of antigenicity and immunogenicity resulted that 22 proteins were antigenic while 6 were non-antigenic on the scale of 0.4 threshold value of VaxiJen. These proteins successfully simulated the immune system in silico and in response higher amount of antibodies' titers were recorded in C-IMMSIM, confirming the immunogenic nature of these proteins. The identified proteins are of diverse nature and functions including those involved in virulence and pathogenesis, energy metabolism, cell development, biosynthesis of amino acids, regulatory functions and biosynthesis of cofactors. The findings of this study would be helpful in the development of improved vaccines and diagnostic tools for typhoid fever.

Non-Obstructive Coronaries In Patients Presenting With The Non St-Elevation Acute Coronary Syndrome.

BACKGROUND: Worldwide, cardiovascular diseases are the major cause of mortality and morbidity with acute coronary syndrome as the most common clinical manifestation. In a typical clinical setup, around 30% of the patients presented with "ST-segment elevation myocardial infarction (STEMI)" caused by the complete occlusion of the coronary artery and the remaining 70% with intermittent or partial occlusion of the coronary termed as non-ST elevation The aim of this study was to assess the prevalence and characteristics of non-obstructive coronary arteries among patients presenting with non ST-elevation acute coronary syndrome (NSTE-ACS) at a tertiary care cardiac center of Karachi, Pakistan. METHODS: This was a descriptive cross-sectional study, conducted at a tertiary care hospital in Karachi. Study inclusion criteria were patients of either gender admitted with NSTE-ACS and aged between 30-70 years. A routine coronary angiogram was performed in all the patients and the absence of ≥50% stenosis in any major epicardial vessel was taken in non-obstructive coronaries. RESULTS: A total of 174 patients (30-70 years) were included, of which 99 (56.9%) were male and the mean age was 59.43±11.24 years. In the distribution of socioeconomic status, 54 (31.0%) were lower class, middle class 81 (46.6%) while upper-class status were 39 (22.4%). Hypertension was observed in 76 (43.7%), chronic kidney disease in 20 (11.5%), and hyperlipidemia in 55 (31.6%). Non-obstructive coronary arteries were noted in 25 (14.4%) patients. CONCLUSIONS: It is to be concluded that non-obstructive coronary arteries are fairly prevalent in patients arriving in hospitals with NSTE-ACS in our population. Further research is needed to better understand the underlying pathophysiology and optimal management strategies for patients with NOCA in the setting of NSTEMI.

Timi Risk Index, A Simple Tool In Emergency Percutaneous Revascularization For The Prediction Of Contrast Induced Nephropathy.

BACKGROUND: Contrast induced nephropathy (CIN) is a common complication seen after primary percutaneous coronary intervention (PCI) which can contribute to increased morbidity and mortality in patients of acute ST elevation myocardial infarction (STEMI). Aim of this study was to validate the TIMI Risk Index (TRI) for the risk stratification of CIN in patients undergone primary PCI. METHODS: Consecutive patients of STEMI undergone primary PCI at a tertiary care cardiac center were included for this study. Patients in Killip class IV at presentation, patients with history of any PCI and chronic kidney diseases were excluded from this study. TRI was calculated using the formula " " and post-procedure serum creatinine level increase of either 25% or 0.5 mg/dL was taken as CIN. RESULTS: A total of 507 patients were included in this study out of which 82.2% were males and 17.8% were females. In total 8.7% (44) patients developed CIN. In the receiver operating characteristic (ROC) curve analysis, area under the curve (AUC) for TRI was found to be 0.717, [0.649-0.758] for the prediction of CIN. Sensitive, specificity, positive predictive value and negative predictive value of TRI >22.8 to predict the development of CIN were 59.09%, 76.69%, 19.55% and 95.19% respectively. CONCLUSIONS: TIMI risk index is and easy to calculate and readily accessible score which has good predictive value to evaluate the risk of CIN in primary PCI setting.

Prospective Validation Of Heart Score For Suspected Acute Coronary Syndrome Patients.

BACKGROUND: The HEART score is reported to be a useful tool for the assessment of suspected acute coronary syndrome (ACS) patients, however, data regarding its validity in our population is scarce. Therefore, aim of this study was to evaluate the prognostic utility of the HEART score to predict major adverse cardiac events (MACE) within 6 weeks in patients presenting to emergency department with chest pain. METHODS: This prospective observational study included suspected ACS patients presented with chest pain to the emergency department of a tertiary care cardiac center. Inclusion criteria for the study were consecutive adult patients with suspected ACS, patients with definite diagnosis of ACS based on history, electrocardiography (ECG), and cardiac enzymes were excluded from the study. HEART score was calculated and patients with ≥7 score were also excluded. MACE over the 6-weeks after discharge were observed. RESULTS: Total of 281 patients were included in this analysis, 191 (68%) were male and mean age was 52.58±10.63 years. Mean HEART score was calculated to be 4.27±1.06 with 70.8% (199) in moderate risk [4-6]. Area under the curve of HEART score for the prediction of 6-weeks MACE was 0.874 [0.827-0.920] with MACE rate of 31.7% vs. 0% for low- and moderate-risk group respectively. CONCLUSIONS: HEART score showed good discriminating power for the prediction of 6-weeks MACE. Risk of MACE for the patients with HEART score of 0-3 is very low and such patients can be discharged from ER without extensive cardiac workup with proper follow-up planned.

The Road to Unconventional Detections: Paper-Based Microfluidic Chips.

Conventional detectors are mostly made up of complicated structures that are hard to use. A paper-based microfluidic chip, however, combines the advantages of being small, efficient, easy to process, and environmentally friendly. The paper-based microfluidic chips for biomedical applications focus on efficiency, accuracy, integration, and innovation. Therefore, continuous progress is observed in the transition from single-channel detection to multi-channel detection and in the shift from qualitative detection to quantitative detection. These developments improved the efficiency and accuracy of single-cell substance detection. Paper-based microfluidic chips can provide insight into a variety of fields, including biomedicine and other related fields. This review looks at how paper-based microfluidic chips are prepared, analyzed, and used to help with both biomedical development and functional integration, ideally at the same time.

Analysis of associated risk factors among recurrent cutaneous leishmaniasis patients: A cross-sectional study in Khyber Pakhtunkhwa, Pakistan.

BACKGROUND: Leishmaniasis is the second and fourth highest cause of mortality and morbidity respectively among all tropical diseases. Recurrence in the onset of leishmaniasis is a major problem that needs to be addressed to reduce the case fatality rate and ensure timely clinical intervention. Here we are investigating the association of risk factors with recurrent cutaneous leishmaniasis to address this issue. MATERIAL AND METHODS: Patients received by Nasser Ullah Khan Babar Hospital in Peshawar, Pakistan from March 2019 to July 2020 were enrolled in this study. Those patients who developed symptoms after completion of treatment were included in Group-A while those who had atypical scars like leishmaniasis but were negative for cutaneous leishmaniasis were included in the comparison group tagged as Group B. All those individuals who had completed six weeks of treatment for CL but had normal complete blood counts (CBC) were included to avoid other underlying immunological pathologies, while we excluded those participants who had co-morbidities like diabetes, liver disease, cardiac disease, and pregnant and lactating women through their history Association was tested between Group-A and Group-B with other explanatory variables through chi-square test. The regression model was proposed to determine the predictors. RESULT: A total of 48 participants of both sexes were included in the study with a mean age of 32.2 ± 15.10. The data suggest that females are overrepresented among the patients with recurrent leishmaniasis [21(53.8 %,); p = 0.07]. Compared to patients; healthy participants had a higher proportion of adults (19-59 years) versus adolescents (13-18 years) [26(66.7 %) vs 07(17.9), p = 0.004]. Multivariate logistic regression analysis shows that females are 2.1 times more prone to infections among cases as compared to healthy individuals [unadjusted OR 2.20, 95 % confidence interval (CI) 1.5-10.6, p = 0.02; adjusted OR 2.1, 95 % CI 1.50-10.69, p = 0.02]. We propose that patients receiving intradermal were less likely to be infected as compared to those receiving intralesional injections [unadjusted OR 0.07.0, 95 % confidence interval (CI) 1.18-3.37, p = 0.03; adjusted OR 0.06, 95 % CI 1.18-3.38, p = 0.03]. CONCLUSION: Old age (adults) and sex (females) were the strongest predictors to be associated with recurrent leishmaniasis. Similarly, the choice of intradermal as compared to intralesional injection and the prolonged treatment duration were strongly associated with greater chances of recurrence.

The explorations of dynamic interactions of paxillin at the focal adhesions.

Paxillin is one of the most important adapters in integrin-mediated adhesions that performs numerous crucial functions relying on its dynamic interactions. Its structural behavior serves different purposes, providing a base for several activities. The various domains of paxillin display different functions in the whole process of cell movements and have a significant role in cell adhesion, migration, signal transmission, and protein-protein interactions. On the other hand, some paxillin-associated proteins provide a unique spatiotemporal mechanism for regulating its dynamic characteristics in the tissue homeostasis and make it a more complex and decisive protein at the focal adhesions. This review briefly describes the structural adaptations and molecular mechanisms of recruitment of paxillin into adhesions, explains paxillin's binding dynamics and impact on adhesion stability and turnover, and reveals a variety of paxillin-associated regulatory mechanisms and how paxillin is embedded into the signaling networks.

Synthesis of novel N-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-{[5-(un/substituted-phenyl)-1,3,4-oxadiazol-2-yl]sulfanyl}acetamides as potent antibacterial agents.

The synthetic methodology was initiated by reacting 1,4-benzodioxane-6-amine (1) with 2-bromoacetyl bromide (2) in aqueous alkaline media under dynamic pH control to get compound 2,3-dihydro-1,4-benzodioxin-6-yl-2-bromoacetamide (3). In the subsequent reactions, a variety of un/substituted-benzoic acids (4a-k), through a succession of three steps, was converted into respective oxadiazole nucleophiles, 7a-k. Finally, the targeted molecules, 8a-k, were obtained by reacting 7a-k with electrophile 3 in an aprotic polar solvent. These compounds were corroborated by spectral characterization like IR, EI-MS, 1H-NMR, and CHN analysis data. These molecules were screened for their antibacterial potential and most of them exhibited a potent activity. Moreover, their cytotoxicity was profiled through hemolytic activity and it was observed that majority of them was very modest in toxicity.

Epidemiological and hematological investigation of dengue virus infection.

Dengue is a mosquito-borne viral illness that infects humans. For the past few decades, it has been declared a global public health problem. The current study, conducted at the district headquarter hospital (DHQ) Bannu between June to September 2018, was based on the seroprevalence of antibodies against dengue virus serotypes and their hematological parameters among the patients. A total of 1738 individuals suspected of having dengue were diagnosed through NS1, IgG, and IgM antibodies and RT-PCR techniques. Of all the samples, 716 (41.19%) were found to be positive for dengue. A higher infection rate was found in males (65.92%) compared with females (34.07%). The most affected age group was 16-40 years, whereas the most affected tehsil was Bannu, where the DENV-3 serotype was prevalent. The rare serotype (DENV-4) was found in 1% of cases. Symptoms including fever (100%), myalgia (100%), headache (61.31%), vomiting (34.63%), and rashes were common among the dengue patients. However, the mild cases showed fewer clinical signs compared with the severely infected cases. The study also revealed a significant association (P < 0.05) between hematological parameters and dengue infection, showing a significant decrease in TC, eosinophils, neutrophils, and platelets and a significant increase in monocytes and lymphocytes. Based on the current report, it is concluded that patients with the above symptoms and hematological changes may have an increased probability of dengue and should be kept under observation to separate dengue-positive patients and to enhance the treatment process.

Synthesis and evaluation of novel 1, 2, 4-substituted triazoles for urease and anti-proliferative activity.

1,2,4-triazoles are a major group of heterocyclic compounds. In the current work, a concise library of such triazoles synthesized through a multistep protocol. The synthesis involved hydrazinolysis of ethyl-2-(p-Cl-phenoxy) acetate followed by reflux with phenyl isothiocyanate to yield the intermediate 2-[2-(p-Cl-phenoxy)acetyl)-N-phenyl-hydrazinecarbothioamide. This intermediate was then cyclized to form 5-[p-(Cl-phenoxy)-methyl]-4-phenyl-4H-1,2,4-triazole-3-thiol (the parent moiety) at alkaline pH. In parallel, 3-bromopropionyl bromide was reacted with a series of phenylamines to yield N-(substituted-phenyl)bromopropanamides. In the final step, N-substitution of 5-[p-(Cl-phenoxy)-methyl]-4- phenyl-4H-1,2,4-triazole-3-thiol was carried out with N-(substituted-phenyl)bromopropanamides to give desired library of 3-[5-[(p-Cl-phenoxy)-methyl]-4- phenyl-4H-1,2,4-triazole-3-ylthio]-N-(substituted-phenyl) propan-amides (8a-l). The prepared moieties were identified via IR, NMR, & EIMS and evaluated for urease and anti-proliferative activities. 3-[5-[(p-Cl-phenoxy)-methyl]-4- phenyl-4H-1,2,4-triazole-3-ylthio]-N-(3-methyl-phenyl)propanamide 8k, was found to be most prominent hit as urease inhibitor (IC50= 42.57± 0.13 µM) using thiourea as standard (IC50= 21.25±0.15µM). The interaction of 8k with urease were studied using docking studies. Anti-proliferative activity results showed 8k as promising candidates and rest of the synthesized derivatives were found to be moderately anti-proliferative. Molecular docking results also displayed 8k, 8h, and 8c as potential hits for further study.

The raft cytoskeleton binding protein complexes personate functional regulators in cell behaviors.

Several cytoskeleton proteins interact with raft proteins to form raft-cytoskeleton binding protein complexes (RCPCs) that control cell migration and adhesion. The purpose of this paper is to review the latest research on the modes and mechanisms by which a RCPC controls different cellular functions. This paper discusses RCPC composition and its role in cytoskeleton reorganization, as well as the latest developments in molecular mechanisms that regulate cell adhesion and migration under normal conditions. In addition, the role of some external stimuli (such as stress and chemical signals) in this process is further debated, and meanwhile potential mechanisms for RCPC to regulate lipid raft fluidity is proposed. Thus, this review mainly contributes to the understanding of RCPC signal transduction in cells. Additionally, the targeted signal transduction of RCPC and its mechanism connection with cell behaviors will provide a logical basis for the development of unified interventions to combat metastasis related dysfunction and diseases.

A systematic review on active sites and functions of PIM-1 protein.

The Proviral Integration of Molony murine leukemia virus (PIM)-1 protein contributes to the solid cancers and hematologic malignancies, cell growth, proliferation, differentiation, migration, and other life activities. Many studies have related these functions to its molecular structure, subcellular localization and expression level. However, recognition of specific active sites and their effects on the activity of this constitutively active kinase is still a challenge. Based on the close relationship between its molecular structure and functional activity, this review covers the specific residues involved in the binding of ATP and different substrates in its catalytic domain. This review then elaborates on the relevant changes in protein conformation and cell functions after PIM-1 binds to different substrates. Therefore, this intensive study can improve the understanding of PIM-1-regulated signaling pathways by facilitating the discovery of its potential phosphorylation substrates.