Nucleotide and codon usage biases involved in the evolution of African swine fever virus: A comparative genomics analysis.

Since African swine fever virus (ASFV) replication is closely related to its host's machinery, codon usage of viral genome can be subject to selection pressures. A better understanding of codon usage can give new insights into viral evolution. We implemented information entropy and revealed that the nucleotide usage pattern of ASFV is significantly associated with viral isolation factors (region and time), especially the usages of thymine and cytosine. Despite the domination of adenine and thymine in the viral genome, we found that mutation pressure alters the overall codon usage pattern of ASFV, followed by selective forces from natural selection. Moreover, the nucleotide skew index at the gene level indicates that nucleotide usages influencing synonymous codon bias of ASFV are significantly correlated with viral protein hydropathy. Finally, evolutionary plasticity is proved to contribute to the weakness in synonymous codons with A- or T-end serving as optimal codons of ASFV, suggesting that fine-tuning translation selection plays a role in synonymous codon usages of ASFV for adapting host. Taken together, ASFV is subject to evolutionary dynamics on nucleotide selections and synonymous codon usage, and our detailed analysis offers deeper insights into the genetic characteristics of this newly emerging virus around the world.

A comparative transcriptome and proteomics study of post-partum ovarian cycle arrest in yaks (Bos grunniens).

Post-partum ovarian cycle arrest is the main factor affecting yak reproductive efficiency. There are few reports regarding the molecular regulatory mechanism of post-partum oestrus at transcriptome and proteome levels in yaks. Our previous studies focussed on the ovaries of yaks with post-partum ovarian cycle arrest and post-partum oestrus yaks. In this study, RNA sequencing transcriptomic study was combined with quantitative proteomic analyses to identify post-partum ovarian cycle-related genes and proteins. Consequently, 1,149 genes and 24 proteins were found to be up- or downregulated during post-partum oestrus. The analysis of differentially regulated genes identified three gene or protein pairs that were synchronously upregulated and no gene or protein pairs that were synchronously downregulated, suggesting that these upregulated genes may regulate the post-partum ovarian cycle. The functional classification of these differentially expressed genes and proteins indicated their connection with the oocyte meiosis, the oestrogen signalling pathway, the progesterone-mediated oocyte maturation and the gonadotrophin-releasing hormone (GnRH) signalling pathway. In this study, a total of six genes and two proteins involved in the oocyte meiosis, the oestrogen signalling pathway, the progesterone-mediated oocyte maturation and the GnRH signalling pathway were identified. The CSNK1A1, M91_09723, M91_11326, M91_21439, M91_19073, SHC2, Atf6b, M91_03062, HSPCA and calmodulin could regulate oestrus, respectively, in the post-partum so as to control the anoestrus status.

The nucleotide usages significantly impact synonymous codon usage in Mycoplasma hyorhinis.

Five annotated genomes of Mycoplasma hyorhinis were analyzed for clarifying evolutionary dynamics driving the overall codon usage pattern. Information entropy used for estimating nucleotide usage pattern at the gene level indicates that multiple evolutionary dynamics participate in forcing nucleotide usage bias at every codon position. Moreover, nucleotide usage bias directly contributes to synonymous codon usage biases with two different extremes. The overrepresented codons tended to have A/T in the third codon position, and the underrepresented codons strongly used G/C in the third position. Furthermore, correspondence analysis and neutrality plot reflect an obvious interplay between mutation pressure and natural selection mediating codon usage in M. hyorhinis genome. Due to significant bias in usages between A/T and G/C at the gene level, different selective forces have been proposed to contribute to codon usage preference in M. hyorhinis genome, including nucleotide composition constraint derived from mutation pressure, translational selection involved in natural selection, and strand-specific mutational bias represented by different nucleotide skew index. The systemic analyses of codon usage for M. hyorhinis can enable us to better understand the mechanisms of evolution in this species.

Zr-MOFs loaded on polyurethane foam by polydopamine for enhanced dye adsorption.

Zirconium-based metal-organic frameworks (Zr-MOFs) have attracted widespread attention due to their high specific surface area, high porosity, abundant metal active sites and excellent hydrothermal stability. However, Zr-MOFs materials are mostly powdery in nature and thus difficult to separate from aqueous media, which limits their application in wastewater treatment. In this study, PDA/Zr-MOFs/PU foam was constructed by growing Zr-MOFs nanoparticles on a dopamine-modified polyurethane foam substrate by in-situ hydrothermal synthesis as an adsorbent for removing dyes from wastewater. The results demonstrated that the polydopamine coating improves the dispersion of the Zr-MOFs nanoparticles on the substrate and enhances the interaction between the Zr-MOFs nanoparticles and the PU foam substrate. As a result, compared with Zr-MOFs/PU foam, the prepared PDA/Zr-MOFs/PU foam exhibits higher adsorption capacity for crystal violet (CV) (63.38 mg/g) and rhodamine B (RB) (67.73 mg/g), with maximum adsorption efficiencies of CV and RB of 98.4% (pH=11) and 93.5% (pH=7), respectively, at a concentration of 10 mg/L. The PDA/Zr-MOFs/PU foam can simultaneously remove CV and RB from the mixed solution. Moreover, the PDA/Zr-MOFs/PU foam still exhibits high stability and reusability after five cycles.

Comparative effects of green and black tea extracts on lowering serum uric acid in hyperuricemic mice.

CONTEXT: Tea (Camellia sinensis (L.) Kuntze [Theaceae]) is used to induce urination and inducing nervous excitation. Green and black teas have multifarious physiological functions. The different effects of green and black tea aqueous extracts (GTEs and BTEs) on hyperuricemia are not definitely reported. OBJECTIVE: The different effects of GTEs and BTEs on lowering serum uric acid (UA) in hyperuricemic mice were determined. MATERIALS AND METHODS: Kunming mice were divided into nine groups (n = 6/each group). GTEs and BTEs at the doses of 0.5, 1 and 2 g/kg were orally administrated to mice for seven days, respectively. Hepatic xanthine oxidase (XOD) and adenosine deaminase (ADA) activities as mechanisms of actions were assessed. RESULTS: Research indicated that the LD50 of tea extract is greater than 2 g/kg in mice. UA levels were suppressed significantly with dose-dependent treatment of 0.5, 1 and 2 g/kg BTEs (up to 25.5%, 28.7% and 29.8%, respectively); the serum UA levels were decreased by GTEs but not significant. The activities of XOD and ADA in high dose (2 g/kg) groups of both GTEs and BTEs were notably lower than those of the model group. DISCUSSION AND CONCLUSIONS: The results suggested that both GTEs and BTEs have hypouricaemic and renal protective effects on hyperuricemic mice and the latter one was better. Our study sheds light on the research and development of anti-hyperuricemic functional foods and drugs from tea.

The mysterious association between adiponectin and endometriosis.

Adiponectin is a pleiotropic cytokine predominantly derived from adipose tissue. In addition to its role in regulating energy metabolism, adiponectin may also be related to estrogen-dependent diseases, and many studies have confirmed its involvement in mediating diverse biological processes, including apoptosis, autophagy, inflammation, angiogenesis, and fibrosis, all of which are related to the pathogenesis of endometriosis. Although many researchers have reported low levels of adiponectin in patients with endometriosis and suggested that it may serve as a protective factor against the development of the disease. Therefore, the purpose of this review was to provide an up-to-date summary of the roles of adiponectin and its downstream cytokines and signaling pathways in the aforementioned biological processes. Further systematic studies on the molecular and cellular mechanisms of action of adiponectin may provide novel insights into the pathophysiology of endometriosis as well as potential therapeutic targets.

Genome-wide identification and functional analysis of the SiCIN gene family in foxtail millet (Setaria italica L.).

Cell wall invertase (CIN) is a vital member of plant invertase (INV) and plays a key role in the breakdown of sucrose. This enzyme facilitates the hydrolysis of sucrose into glucose and fructose, which is crucial for various aspects of plant growth and development. However, the function of CIN genes in foxtail millet (Setaria italica) is less studied. In this research, we used the blast-p of NCBI and TBtools for bidirectional comparison, and a total of 13 CIN genes (named SiCINs) were identified from foxtail millet by using Arabidopsis and rice CIN sequences as reference sequences. The phylogenetic tree analysis revealed that the CIN genes can be categorized into three subfamilies: group 1, group 2, and group 3. Furthermore, upon conducting chromosomal localization analysis, it was observed that the 13 SiCINs were distributed unevenly across five chromosomes. Cis-acting elements of SiCIN genes can be classified into three categories: plant growth and development, stress response, and hormone response. The largest number of cis-acting elements were those related to light response (G-box) and the cis-acting elements related to seed-specific regulation (RY-element). qRT-PCR analysis further confirmed that the expression of SiCIN7 and SiCIN8 in the grain was higher than that in any other tissues. The overexpression of SiCIN7 in Arabidopsis improved the grain size and thousand-grain weight, suggesting that SiCIN7 could positively regulate grain development. Our findings will help to further understand the grain-filling mechanism of SiCIN and elucidate the biological mechanism underlying the grain development of SiCIN.

Zeolitic imidazolate framework-L loaded on melamine foam for removal tetracycline hydrochloride from water.

Zeolitic imidazolate framework-L/melamine foam (ZIF-L/MF) is fabricated by an in situ growth method to treat the tetracycline hydrochloride in wastewater. The results show that a large amount of leaf-like ZIF-L is vertically grown on the MF surface. ZIF-L/MF exhibits well adsorption performance with a maximum adsorption ability of 1346 mg/g. The pseudo-second-order kinetic model and the Langmuir isotherm model are used to describe the adsorption process well. In addition, the influences of pH and coexisting ions are studied. According to the experimental data and analysis, the adsorption mechanisms may involve H-bonding, π-π interaction, and weak electrostatic interaction. A dynamic adsorption experiment is also performed, and the results show that the time required to achieve the same removal efficiency as static adsorption is reduced by half. This work shows that the obtained ZIF-L/MF has practical applications in antibiotic adsorption.

Effect of Thermal Exposure on Microstructure Evolution and Mechanical Properties of TC25G Alloy.

The microstructure and room temperature tensile properties of heat-treated TC25G alloy after thermal exposure were investigated. The results show that the α2 phase dispersed in the α phase, and silicide precipitated firstly at the α/ß phase boundary and then at the dislocation of the αp phase and on the ß phase. When thermal exposure was 0-10 h at 550 °C and 600 °C, the decrease of alloy strength was mainly due to the dominant effect of dislocations recovery. With the rise and extension of thermal exposure temperature and time, the increasing quantity and size of precipitates played an important role in the improvement of alloy strength. When thermal exposure temperature rose to 650 °C, the strength was always lower than that of heat-treated alloy. However, since the decreasing rate of solid solution strengthening was smaller than the increasing rate of dispersion strengthening, alloy still showed an increasing trend in the range of 5-100 h. When thermal exposure time was 100-500 h, the size of the α2 phase increased from the critical value of 3 nm to 6 nm, and the interaction between the moving dislocations and the α2 phase changed from the cutting mechanism to the by-pass mechanism (Orowan mechanism), and thus alloy strength decreased rapidly.

Large-scale metabolome analysis reveals dynamic changes of metabolites during foxtail millet grain filling.

Compared with traditional staple crops, foxtail millet grain is rich in nutrition and beneficial to human health. Foxtail millet is also tolerance to various abiotic stresses, including drought, making it a good plant for growing in barren land. The study on the composition of metabolites and its dynamics changes during grain development is helpful to understand the process of foxtail millet grain formation. In our study, metabolic and transcriptional analysis were used to uncover the metabolic processes that could influence grain filling in foxtail millet. A total of 2104 known metabolites, belonging to 14 categories, were identified during grain filling. Functional analysis of DAMs and DEGs revealed a stage-specific metabolic properties in foxtail millet grain filling. Some important metabolic processes, such as flavonoid biosynthesis, glutathione metabolism, linoleic acid metabolism, starch and sucrose metabolism and valine, leucine and isoleucine biosynthesis were co-mapped for DEGs and DAMs. Thus, we constructed a gene-metabolite regulatory network of these metabolic pathways to explain their potential functions during grain filling. Our study showed the important metabolic processes during grain filling and focused on the dynamic changes of related metabolites and genes at different stages, which provided a reference for us to better understand and improve foxtail millet grain development and yield.

Energy Storage Mechanism in Supercapacitors with Porous Graphdiynes: Effects of Pore Topology and Electrode Metallicity.

Porous graphdiynes are a new class of porous 2D materials with tunable electronic structures and various pore structures. They have potential applications as well-defined nanostructured electrodes and can provide platforms for understanding energy storage mechanisms underlying supercapacitors. Herein, the effect of stacking structure and metallicity on energy storage with such electrodes is investigated. Simulations reveal that supercapacitors based on porous graphdiynes of AB stacking structure can achieve both higher double-layer capacitance and ionic conductivity than AA stacking. This phenomenon is ascribed to more intense image forces in AB stacking, leading to a breakdown of ionic ordering and the formation of effective "free ions". Macroscale analysis shows that doped porous graphdiynes can deliver outstanding gravimetric and volumetric energy and power densities due to their enhanced quantum capacitance. These findings pave the way for designing high-performance supercapacitors by regulating pore topology and metallicity of electrode materials.

Effect of Chemical Activation on Surface Properties of Poly(tetrafluoroethylene-co-hexafluoropropylene) Film.

Due to their low surface energy, poly(tetrafluoroethylene-co-hexafluoropropylene) (FEP) films must be treated by chemical or physical activation methods before using. Among these activation strategies, using sodium naphthalene solution is a popular one. However, the effect of this strategy's chemical activation conditions on the surface properties of the FEP film is rarely discussed. In this study, FEP films were chemically activated by the sodium naphthalene solution with adjusting concentration, solvent, and activation time. With increasing concentration and activation time, many granular substances appeared on the surface of the FEP film. When tetrahydrofuran was used as a solvent, the color of the film gradually turned brown; when 1,3-dimethyl-2-imidazolidinone was chosen as the solvent, the color change was not very significant. The contact angle was significantly reduced from 112° before activation to 26° after activation, and the surface energy was greatly enhanced from 34 mN m-1 before activation to 66 mN m-1 after activation. In addition, compared with the FEP samples treated by Ar plasma, the sodium naphthalene system showed a stronger activation ability. Activated FEP films that suffered from the Ar plasma treatment could still maintain a higher energy surface than that of the pristine FEP.

Role of Ginseng, Quercetin, and Tea in Enhancing Chemotherapeutic Efficacy of Colorectal Cancer.

As the most common gastrointestinal malignancy, colorectal cancer (CRC) remains a leading cause of cancer death worldwide. Although multimodal chemotherapy has effectively improved the prognosis of patients with CRC in recent years, severe chemotherapy-associated side effects and chemoresistance still greatly impair efficacy and limit its clinical application. In response to these challenges, an increasing number of traditional Chinese medicines have been used as synergistic agents for CRC administration. In particular, ginseng, quercetin, and tea, three common dietary supplements, have been shown to possess the potent capacity of enhancing the sensitivity of various chemotherapy drugs and reducing their side effects. Ginseng, also named "the king of herbs", contains a great variety of anti-cancer compounds, among which ginsenosides are the most abundant and major research objects of various anti-tumor studies. Quercetin is a flavonoid and has been detected in multiple common foods, which possesses a wide range of pharmacological properties, especially with stronger anti-cancer and anti-inflammatory effects. As one of the most consumed beverages, tea has become particularly prevalent in both West and East in recent years. Tea and its major extracts, such as catechins and various constituents, were capable of significantly improving life quality and exerting anti-cancer effects both in vivo and in vitro. In this review, we mainly focused on the adjunctive effects of the three herbs and their constituents on the chemotherapy process of CRC.

In-Situ Study on Tensile Deformation and Fracture Mechanisms of Metastable ß Titanium Alloy with Equiaxed Microstructure.

Understanding the mechanisms of deformation and fracture of metastable ß titanium alloys is of great significance for improving formability and service life. By combining the in-situ tensile test, TEM characterization and EBSD analysis, the tensile deformation behavior, activation of slip systems, crack initiation, and propagation of a high strength metastable ß titanium alloy (Ti-5Cr-4Al-4Zr-3Mo-2W-0.8Fe) with equiaxed microstructure are investigated. The equiaxed microstructure is composed of primary α (αp) phase, transformed ß (ßt) matrix phase, and secondary α (αs) phase. In contrast to the hexagonal αp grain with limited slip systems, the body-centered ßt matrix has more slip systems, however the hindering effect of αs phases on dislocation slip leads to the different deformability of the αp phase and ßt matrix. The equiaxed αp grains are more prone to deformation and rotation to coordinate the overall deformation. The shear band leads to the formation of sub-grain boundary and even the fragmentation of αp grains. As a result, the microvoids tend to nucleate at the grain boundary, phase interface, slip band, and shear band. The inhomogeneous deformation in the plastic deformation zone around the crack tip is the primary cause of damage. The crack propagation caused by microvoids coalescence advances along the grain boundaries and phase interfaces in the form of intergranular, and along the activated slip systems and shear bands in the form of transgranular. Pinpointing the situation in the equiaxed microstructure and combining that in other typical microstructures will help to summarize the universal deformation and fracture mechanisms of metastable ß titanium alloy, and provide a basis for alloy design and microstructure tailoring.

Risk Factors and Preventive Measures for Anastomotic Leak in Colorectal Cancer.

Anastomotic leak (AL) represents one of the most detrimental complications after colorectal surgery. The patient-related factors and surgery-related factors leading to AL have been identified in previous studies. Through early identification and timely adjustment of risk factors, preventive measures can be taken to reduce potential AL. However, there are still many problems associated with AL. The debate about preventive measures such as preoperative mechanical bowel preparation (MBP), intraoperative drainage, and surgical scope also continues. Recently, the gut microbiota has received more attention due to its important role in various diseases. Although the underlying mechanisms of gut microbiota on AL have not been validated completely, new strategies that manipulate intrinsic mechanisms are expected to prevent and treat AL. Moreover, laboratory examinations for AL prediction and methods for blood perfusion assessment are likely to be promoted in clinical practice. This review outlines possible risk factors for AL and suggests some preventive measures in terms of patient, surgery, and gut microbiota.

Transcriptome and proteome analysis of pregnancy and postpartum anoestrus ovaries in yak.

BACKGROUND: Domestic yaks are the most important livestock species on the Qinghai-Tibetan Plateau. Adult female yaks normally breed in the warm season (July to September) and enter anestrous in the cold season (November to April). Nevertheless, it is unclear how ovarian activity is regulated at the molecular level. OBJECTIVES: The peculiarities of yak reproduction were assessed to explore the molecular mechanism of postpartum anestrus ovaries in yaks after pregnancy and parturition. METHODS: Sixty female yaks with calves were observed under natural grazing in Haiyan County, Qinghai Province. Three yak ovaries in pregnancy and postpartum anestrus were collected. RNA sequencing and quantitative proteomics were employed to analyze the pregnancy and postpartum ovaries after hypothermia to identify the genes and proteins related to the postpartum ovarian cycle. RESULTS: The results revealed 841 differentially expressed genes during the postpartum hypoestrus cycle; 347 were up-regulated and 494 genes were down-regulated. Fifty-seven differential proteins were screened: 38 were up-regulated and 19 were down-regulated. The differential genes and proteins were related to the yak reproduction process, rhythm process, progesterone-mediated oocyte maturation, PI3K/AKT signaling pathway, and MAPK signaling pathway categories. CONCLUSIONS: Transcriptome and proteomic sequencing approaches were used to investigate postpartum anestrus and pregnancy ovaries in yaks. The results confirmed that BHLHE40, SF1IX1, FBPX1, HSPCA, LHCGR, BMP15, and ET-1R could affect postpartum hypoestrus and control the state of estrus.

The expression of αA- and ßB1-crystallin during normal development and regeneration, and proteomic analysis for the regenerating lens in Xenopus laevis.

PURPOSE: To explore the expression of the lens crystallins (αA- and ßB1-crystallin) in Xenopus laevis embryonic lens development and regeneration and to analyze the order of different crystallins generated in the regenerating lens. METHODS: Real Time-PCR, Immunofluorescence, and 2D-PAGE were used to analyze the expressions of αA-crystallin and ßB1-crystallin, and related factors during embryonic lens development and regeneration in Xenopus laevis. RESULTS: αA-crystallin and ßB1-crystallin were first detected at stage 29/30 during normal development, and the two crystallins were simultaneously detected in regeneration. During embryonic lens development, the relative expression level of the ßB1-crystallin gene was higher than that of the αA-crystallin gene. In the process of the lens regeneration, however, the relative expression level of the ßB1-crystallin gene was lower than that of the αA-crystallin gene. Throughout embryonic lens development, the two crystallin transcripts showed the same variation trends, and similar occurrence did in the regeneration process. Crystallins showed different localization and distribution during the ontogeny and regeneration, especially in the lens fiber region. 2D-electrophores revealed the patterns of the sequential synthesis of crystallins, with regard to the different classes and apparent variations of some auxiliary regulatory factors. CONCLUSIONS: The ontogeny and localization of the crystallins during embryonic lens development and regeneration indicated a different development program, although they have identical origins, the ectoderm. The expression level of crystallin transcripts displayed a consistent variation tendency, but the presence of appreciable differences was still exposed. In addition to stably producing the crystallins of different classes in accordance with established procedure, these auxiliary factors may perform the function, to some extent, because of significant changes in their expression throughout the process of lens regeneration.

Interaction between Pax6 and its novel mutant in Bufo raddei Strauch.

PURPOSE: Exploration of the relationship between a novel paired box 6 (Pax6) mutant and Pax6 in Bufo raddei Strauch. METHODS: RT-PCR, yeast 2-hybrid system, and co-immunoprecipitation were used to analyze the Pax6 protein and its mutant during embryonic eye development in Bufo raddei Strauch. RESULTS: We have cloned the Pax6 ORF sequence from Bufo raddei Strauch. Here we report the cloning of a novel Pax6 homolog of Bufo raddei Strauch named Pax6 variant. Comparing the 2 genes, the homolog of ORF nucleotide sequence is more than 99% in Bufo raddei Strauch; only the proline-serine-threonine(PST)-rich transaction domain differs. The deduced amino acid sequences of PST region are 53.1% identical. An interaction was found between Pax6 and Pax6 variant via yeast 2-hybrid system; with further study, we found that they interacted in vivo via co-immunopricipitation. CONCLUSIONS: A Pax6 mutant was first found in Bufo raddei Strauch. Interaction between Pax6 and Pax6 variant may play a critical role during eye development in Bufo raddei Strauch. This suggests that expression of Pax6 variant may play a role and appears to be a necessity in eye development, but that Pax6 itself is still pivotal in eye development.

Quality of life and related factors in adult patients with epilepsy in China.

OBJECTIVE: The objective of this work was to study the quality of life (QOL) of adult patients with epilepsy in northern China. METHODS: Three hundred three adult patients with epilepsy were identified using a strict procedure of diagnosis at the outpatient clinic of the epilepsy center, and then their QOL was evaluated with the Chinese version of the Quality of Life in Epilepsy Inventory-89. RESULTS: QOLIE-89 total score and many of the subscale scores were decreased. The greatest decreases were observed in the Seizure Worry and Medication Effects subscale scores. QOLIE-89 total scores of married patients (57.1±15.3) were lower than those of unmarried patients (70.9±15.7) (P<0.001). Correlation analysis revealed that QOLIE-89 total score was negatively correlated with age, course of disease, seizure severity, antiepileptic drug, type of seizure, and seizure frequency (r=-0.334, -0.281, -0.424, -0.117, -0.145, and -0.274 respectively, P<0.01), and was positively correlated with educational level and economic status (r=0.245 and 0.328 respectively, P<0.01). Multiregression analysis revealed that five factors entered the regression equation: age (ß=-0.545, P=0.001), course of disease (ß=-0.311, P=0.001), seizure severity (ß=-10.014, P=0.001), educational level (ß=3.274, P=0.002), and economic status (ß=6.431, P=0.001). CONCLUSION: Quality of life of adult patients with epilepsy decreases with older age, more difficult course of disease, and higher seizure frequency. Higher educational level and economic status are protective factors in the QOL of adult patients.

Recent strategies for enhancing the therapeutic efficacy of stem cells in wound healing.

Skin wound healing is a multi-stage process that depends on the coordination of multiple cells and mediators. Chronic or non-healing wounds resulting from the dysregulation of this process represent a challenge for the healthcare system. For skin wound management, there are various approaches to tissue recovery. For decades, stem cell therapy has made outstanding achievements in wound regeneration. Three major types of stem cells, including embryonic stem cells, adult stem cells, and induced pluripotent stem cells, have been explored intensely. Mostly, mesenchymal stem cells are thought to be an extensive cell type for tissue repair. However, the limited cell efficacy and the underutilized therapeutic potential remain to be addressed. Exploring novel and advanced treatments to enhance stem cell efficacy is an urgent need. Diverse strategies are applied to maintain cell survival and increase cell functionality. In this study, we outline current approaches aiming to improve the beneficial outcomes of cell therapy to better grasp clinical cell transformation.