PowerNovo: de novo peptide sequencing via tandem mass spectrometry using an ensemble of transformer and BERT models.

The primary objective of analyzing the data obtained in a mass spectrometry-based proteomic experiment is peptide and protein identification, or correct assignment of the tandem mass spectrum to one amino acid sequence. Comparison of empirical fragment spectra with the theoretical predicted one or matching with the collected spectra library are commonly accepted strategies of proteins identification and defining of their amino acid sequences. Although these approaches are widely used and are appreciably efficient for the well-characterized model organisms or measured proteins, they cannot detect novel peptide sequences that have not been previously annotated or are rare. This study presents PowerNovo tool for de novo sequencing of proteins using tandem mass spectra acquired in a variety of types of mass analyzers and different fragmentation techniques. PowerNovo involves an ensemble of models for peptide sequencing: model for detecting regularities in tandem mass spectra, precursors, and fragment ions and a natural language processing model, which has a function of peptide sequence quality assessment and helps with reconstruction of noisy sequences. The results of testing showed that the performance of PowerNovo is comparable and even better than widely utilized PointNovo, DeepNovo, Casanovo, and Novor packages. Also, PowerNovo provides complete cycle of processing (pipeline) of mass spectrometry data and, along with predicting the peptide sequence, involves the peptide assembly and protein inference blocks.

Cytotoxic and radical activities of metal-organic framework modified with iron oxide: Biological and physico-chemical analyses.

Metal-organic framework (MOF) modified with iron oxide, Fe3O4-MOF, is a perspective drug delivery agent, enabling magnetic control and production of active hydroxyl radicals, •OH, via the Fenton reaction. This paper studies cytotoxic and radical activities of Fe-containing nanoparticles (NPs): Fe3O4-MOF and its components - bare Fe3O4 and MOF (MIL-88B). Luminous marine bacteria Photobacteriumphosphoreum were used as a model cellular system to monitor bioeffects of the NPs. Neither the NPs of Fe3O4-MOF nor MOF showed cytotoxic effects in a wide range of concentrations (<10 mg/L); while Fe3O4 was toxic at >3·10-3 mg/L. The NPs of Fe3O4 did not affect the bacterial bioluminescence enzymatic system; their toxic effect was attributed to cellular membrane processes. The integral content of reactive oxygen species (ROS) was determined using a chemiluminescence luminol assay. Bacteria mitigated excess of ROS in water suspensions of Fe3O4-MOF and MOF, maintaining bioluminescence intensity closer to the control; this resulted in low toxicity of these NPs. We estimated the activity of •OH radicals in the NPs samples with physical and chemical methods - spin capture technology (using electron paramagnetic resonance spectroscopy) and methylene blue degradation. Physico-chemical interpretation of cellular responses is provided in terms of iron content, iron ions release and •OH radical production.

First Examples of s-Metal Complexes with Subporphyrazine and Its Phenylene-Annulated Derivatives: DFT Calculations.

Using quantum chemical calculation data obtained by the DFT method with the B3PW91/TZVP and M062X/def2TZVP theory levels, the possibility of the existence of four Be(II) coordination compounds, each of which contains in the inner coordination sphere and the double deprotonated forms of subporphyrazine (H2SP), mono[benzo]subporphyrazine (H2MBSP), di[benzo]subporphyrazine (H2DBSP), and tri[benzo]subporphyrazine (subphthalocyanine) (H2TBSP) with a ratio Be(II) ion/ligand = 1:1, were examined Selected geometric parameters of the molecular structures of these (666)macrotricyclic complexes with closed contours are given; it was noted that BeN3 chelate nodes have a trigonal-pyramidal structure and exhibit a very significant (almost 30°) deviation from coplanarity; however, all three 6-membered metal-chelate and three 5-membered non-chelate rings in each of these compounds are practically planar and deviate from coplanarity by no more than 2.5°. The bond angles between two nitrogen atoms and a Be atom are equal to 60° (in the [BeSP] and [BeTBSP]) or less by no more than 0.5° (in the [BeMBSP] and [BeDBSP]). The presence of annulated benzo groups has little effect on the parameters of the molecular structures of these complexes. Good agreement between the structural data obtained using the above two versions of the DFT method was noticed. NBO analysis data for these complexes are presented; it was noted that, according to both DFT methods used, the ground state of the each of complexes under study is a spin singlet. Standard thermodynamic parameters of formation (standard enthalpy ΔfH0, entropy S0, and Gibbs free energy ΔfG0) for the above-mentioned macrocyclic compounds were calculated.

Prediction of the Aggressive Clinical Course of Papillary Thyroid Carcinoma Based on Fine Needle Aspiration Biopsy Molecular Testing.

Molecular genetic events are among the numerous factors affecting the clinical course of papillary thyroid carcinoma (PTC). Recent studies have demonstrated that aberrant expression of miRNA, as well as different thyroid-related genes, correlate with the aggressive clinical course of PTC and unfavorable treatment outcomes, which opens up new avenues for using them in the personalization of the treatment strategy for patients with PTC. In the present work, our goal was to assess the applicability of molecular markers in the preoperative diagnosis of aggressive variants of papillary thyroid cancer. The molecular genetic profile (expression levels of 34 different markers and BRAF mutations) was studied for 108 cytology specimens collected by fine-needle aspiration biopsy in patients with PTC having different clinical manifestations. Statistically significant differences with adjustment for multiple comparisons (p < 0.0015) for clinically aggressive variants of PTC were obtained for four markers: miRNA-146b, miRNA-221, fibronectin 1 (FN1), and cyclin-dependent kinase inhibitor 2A (CDKN2A) genes. A weak statistical correlation (0.0015 < p < 0.05) was observed for miRNA-31, -375, -551b, -148b, -125b, mtDNA, CITED1, TPO, HMGA2, CLU, NIS, SERPINA1, TFF3, and TMPRSS4. The recurrence risk of papillary thyroid carcinoma can be preoperatively predicted using miRNA-221, FN1, and CDKN2A genes.

Mts1 (S100A4) and Its Peptide Demonstrate Cytotoxic Activity in Complex with Tag7 (PGLYRP1) Peptide.

Receptors of cytokines are major regulators of the immune response. In this work, we have discovered two new ligands that can activate the TNFR1 (tumor necrosis factor receptor 1) receptor. Earlier, we found that the peptide of the Tag (PGLYRP1) protein designated 17.1 can interact with the TNFR1 receptor. Here, we have found that the Mts1 (S100A4) protein interacts with this peptide with a high affinity (Kd = 1.28 × 10-8 M), and that this complex is cytotoxic to cancer cells that have the TNFR1 receptor on their surface. This complex induces both apoptosis and necroptosis in cancer cells with the involvement of mitochondria and lysosomes in cell death signal transduction. Moreover, we have succeeded in locating the Mts1 fragment that is responsible for protein-peptide interaction, which highly specifically interacts with the Tag7 protein (Kd = 2.96 nM). The isolated Mts1 peptide M7 also forms a complex with 17.1, and this peptide-peptide complex also induces the TNFR1 receptor-dependent cell death. Molecular docking and molecular dynamics experiments show the amino acids involved in peptide binding and that may be used for peptidomimetics' development. Thus, two new cytotoxic complexes were created that were able to induce the death of tumor cells via the TNFR1 receptor. These results may be used in therapy for both cancer and autoimmune diseases.

Free Salivary Amino Acid Profile in Breast Cancer: Clinicopathological and Molecular Biological Features.

The study of salivary amino acid profiles has attracted the attention of researchers, since amino acids are actively involved in most metabolic processes, including breast cancer. In this study, we analyzed the amino acid profile of saliva in a sample including all molecular biological subtypes of breast cancer to obtain a more complete picture and evaluate the potential utility of individual amino acids or their combinations for diagnostic purposes. This study included 116 patients with breast cancer, 24 patients with benign breast disease, and 25 healthy controls. From all patients, strictly before the start of treatment, saliva samples were collected, and the quantitative content of 26 amino acids was determined. Statistically significant differences between the three groups are shown in the content of Asp, Gly, Leu + Ile, Orn, Phe, Pro, Thr, and Tyr. To differentiate the three groups from each other, a decision tree was built. To construct it, we selected those amino acids for which the change in concentrations in the subgroups was multidirectional (GABA, Hyl, Arg, His, Pro, and Car). For the first time, it is shown that the amino acid profile of saliva depends on the molecular biological subtype of breast cancer. The most significant differences are shown for the luminal B HER2-positive and TNBC subgroups. In our opinion, it is critically important to consider the molecular biological subtype of breast cancer when searching for potential diagnostic markers.

Microbicides for Topical HIV Immunoprophylaxis: Current Status and Future Prospects.

Microbicides, which are classified as topical antiseptic agents, are a revolutionary advancement in HIV prevention aimed to prevent the entry of infectious agents into the human body, thus stopping the sexual transmission of HIV and other sexually transmitted diseases. Microbicides represent the promise of a new age in preventive measures against one of the world's most pressing health challenges. In addition to their direct antiviral effects during HIV transmission, microbicides also influence vaginal mucosal immunity. This article reviews microbicides by presenting different drug classifications and highlighting significant representatives from each group. It also explains their mechanisms of action and presents information about vaginal mucosal immune responses, emphasizing the critical role they play in responding to HIV during sexual transmission. The article discusses the following groups of microbicides: surfactants or membrane disruptors, vaginal milieu protectors, anionic polymers, dendrimers, carbohydrate-binding proteins, HIV replication inhibitors (reverse transcriptase inhibitors), and multi-purpose prevention technologies, which combine protection against HIV, other sexually transmitted diseases, and contraception. For each chemical compound, the article provides a brief overview of relevant preclinical and clinical research, emphasizing their potential as microbicides. The article offers insights into the multifaceted impact of microbicides, which signify a pivotal step forward in the pursuit of effective and accessible pre-exposure prophylaxis (PrEP).

Resting-state functional connectivity correlates of brain structural aging in schizophrenia.

A large body of research has shown that schizophrenia patients demonstrate increased brain structural aging. Although this process may be coupled with aberrant changes in intrinsic functional architecture of the brain, they remain understudied. We hypothesized that there are brain regions whose whole-brain functional connectivity at rest is differently associated with brain structural aging in schizophrenia patients compared to healthy controls. Eighty-four male schizophrenia patients and eighty-six male healthy controls underwent structural MRI and resting-state fMRI. The brain-predicted age difference (b-PAD) was a measure of brain structural aging. Resting-state fMRI was applied to obtain global correlation (GCOR) maps comprising voxelwise values of the strength and sign of functional connectivity of a given voxel with the rest of the brain. Schizophrenia patients had higher b-PAD compared to controls (mean between-group difference + 2.9 years). Greater b-PAD in schizophrenia patients, compared to controls, was associated with lower whole-brain functional connectivity of a region in frontal orbital cortex, inferior frontal gyrus, Heschl's Gyrus, plana temporale and polare, insula, and opercular cortices of the right hemisphere (rFTI). According to post hoc seed-based correlation analysis, decrease of functional connectivity with the posterior cingulate gyrus, left superior temporal cortices, as well as right angular gyrus/superior lateral occipital cortex has mainly driven the results. Lower functional connectivity of the rFTI was related to worse verbal working memory and language production. Our findings demonstrate that well-established frontotemporal functional abnormalities in schizophrenia are related to increased brain structural aging.

The metamorphosis of amphibian myocardium: moving to the heart of the matter.

Amphibians are a classical object for physiological studies, and they are of great value for developmental studies owing to their transition from an aquatic larval form to an adult form with a terrestrial lifestyle. Axolotls (Ambystoma mexicanum) are of special interest for such studies because of their neoteny and facultative pedomorphosis, as in these animals, metamorphosis can be induced and fully controlled in laboratory conditions. It has been suggested that their metamorphosis, associated with gross anatomical changes in the heart, also involves physiological and electrical remodeling of the myocardium. We used whole-cell patch clamp to investigate possible changes caused by metamorphosis in electrical activity and major ionic currents in cardiomyocytes isolated from paedomorphic and metamorphic axolotls. T4-induced metamorphosis caused shortening of atrial and ventricular action potentials (APs), with no changes in resting membrane potential or maximum velocity of AP upstroke, favoring higher heart rate possible in metamorphic animals. Potential-dependent potassium currents in axolotl myocardium were represented by delayed rectifier currents IKr and IKs, and upregulation of IKs caused by metamorphosis probably underlies AP shortening. Metamorphosis was associated with downregulation of inward rectifier current IK1, probably serving to increase the excitability of myocardium in metamorphic animals. Metamorphosis also led to a slight increase in fast sodium current INa with no changes in its steady-state kinetics and to a significant upregulation of ICa in both atrial and ventricular cells, indicating stronger Ca2+ influx for higher cardiac contractility in metamorphic salamanders. Taken together, these changes serve to increase cardiac reserve in metamorphic animals.

Expanding phenotype of MED13-associated syndrome presenting novel de novo missense variant in a patient with multiple congenital anomalies.

BACKGROUND: Whole exome sequencing allows rapid identification of causative single nucleotide variants and short insertions/deletions in children with congenital anomalies and/or intellectual disability, which aids in accurate diagnosis, prognosis, appropriate therapeutic interventions, and family counselling. Recently, de novo variants in the MED13 gene were described in patients with an intellectual developmental disorder that included global developmental delay, mild congenital heart anomalies, and hearing and vision problems in some patients. RESULTS: Here we describe an infant who carried a de novo p.Pro835Ser missense variant in the MED13 gene, according to whole exome trio sequencing. He presented with congenital heart anomalies, dysmorphic features, hydrocephalic changes, hypoplastic corpus callosum, bilateral optic nerve atrophy, optic chiasm atrophy, brain stem atrophy, and overall a more severe condition compared to previously described patients. CONCLUSIONS: Therefore, we propose to expand the MED13-associated phenotype to include severe complications that could end up with multiple organ failure and neonatal death.

Development, evaluation and validation of machine learning models to predict hospitalizations of patients with coronary artery disease within the next 12 months.

BACKGROUND: Improved survival of patients after acute coronary syndromes, population growth, and overall life expectancy rise have led to a significant increase in the proportion of patients with stable coronary artery disease (CAD), creating a significant load on the entire healthcare system. The disease often progresses with the development of many complications while significantly increasing the likelihood of hospitalization. Developing and applying a machine learning model for predicting hospitalizations of patients with CAD to an inpatient medical facility will allow for close monitoring of high-risk patients, early preventive interventions, and optimized medical care. AIMS: Development and external validation of personalized models for predicting the preventable hospitalizations of patients with stable CAD and its complications using ML algorithms and data of real-world clinical practice. METHODS: 135,873 depersonalized electronic health records of 49,103 patients with stable CAD were included in the study. Anthropometric measurements, physical examination results, laboratory, instrumental, anamnestic, and socio-demographic data, widely used in routine medical practice, were considered as potential predictors, a total of 73 features. Logistic regression, decision tree-based methods including gradient boosting (AdaBoost, LightGBM, XGBoost, CatBoost) and bagging (RandomForest and ExtraTrees), discriminant analysis (LinearDiscriminant, QuadraticDiscriminant), and naive Bayes classifier were compared. External validation was performed on the data of a separate region. RESULTS: The best results and stability to external validation data were shown by the CatBoost model with an AUC of 0.875 (95% CI 0.865-0.885) for the internal testing and 0.872 (95% CI 0.856-0.886) for the external validation. The best model showed good performance evaluated through AUROC, Brier score and standardized net benefit (for the target NPV threshold) for the validation dataset that was only slightly similar to the train data. CONCLUSION: The metrics of the best model were superior to previously published studies. The results of external validation demonstrated the relative stability of the model to new data from another region that confirms the possibility of the model's application in real clinical practice.

Improving the Adhesion of Multi-Walled Carbon Nanotubes to Titanium by Irradiating the Interface with He+ Ions: Atomic Force Microscopy and X-ray Photoelectron Spectroscopy Study.

A complex study of the adhesion of multi-walled carbon nanotubes to a titanium surface, depending on the modes of irradiation with He+ ions of the "MWCNT/Ti" system, was conducted using atomic force microscopy and X-ray photoelectron spectroscopy. A quantitative assessment of the adhesion force at the interface, performed using atomic force microscopy, demonstrated its significant increase as a result of treatment of the "MWCNT/Ti" system with a beam of helium ions. The nature of the chemical bonding between multi-walled carbon nanotubes and the surface of the titanium substrate, which causes this increase in the adhesion of nanotubes to titanium as a result of ion irradiation, was investigated by X-ray photoelectron spectroscopy. It was established that this bonding is the result of the formation of chemical C-O-Ti bonds between titanium and carbon atoms with the participation of oxygen atoms of oxygen-containing functional groups, which are localized on defects in the nanotube walls formed during ion irradiation. It is significant that there are no signs of direct bonding between titanium and carbon atoms.

3-Methyl-phenanthrene (3-MP) disrupts the electrical and contractile activity of the heart of the polar fish, navaga cod (Eleginus nawaga).

Alkylated polycyclic aromatic hydrocarbons are abundant in crude oil and are enriched during petroleum refinement but knowledge of their cardiotoxicity remains limited. Polycyclic aromatic hydrocarbons (PAHs) are considered the main hazardous components in crude oil and the tricyclic PAH phenanthrene has been singled out for its direct effects on cardiac tissue in mammals and fish. Here we test the impact of the monomethylated phenanthrene, 3-methylphenanthrene (3-MP), on the contractile and electrical function of the atrium and ventricle of a polar fish, the navaga cod (Eleginus nawaga). Using patch-clamp electrophysiology in atrial and ventricular cardiomyocytes we show that 3-MP is a potent inhibitor of the delayed rectifier current IKr (IC50 = 0.25 µM) and prolongs ventricular action potential duration. Unlike the parent compound phenanthrene, 3-MP did not reduce the amplitude of the L-type Ca2+ current (ICa) but it accelerated current inactivation thus reducing charge transfer across the myocyte membrane and compromising pressure development of the whole heart. 3-MP was a potent inhibitor (IC50 = 4.7 µM) of the sodium current (INa), slowing the upstroke of the action potential in isolated cells, slowing conduction velocity across the atrium measured with optical mapping, and increasing atrio-ventricular delay in a working whole heart preparation. Together, these findings reveal the strong cardiotoxic potential of this phenanthrene derivative on the fish heart. As 3-MP and other alkylated phenanthrenes comprise a large fraction of the PAHs in crude oil mixtures, these findings are worrisome for Arctic species facing increasing incidence of spills and leaks from the petroleum industry. 3-MP is also a major component of polluted air but is not routinely measured. This is also of concern if the hearts of humans and other terrestrial animals respond to this PAH in a similar manner to fish.

Near-infrared two-photon excited photoluminescence from Yb3+-doped CsPbClxBr3-x perovskite nanocrystals embedded into amphiphilic silica microspheres.

Nonlinear absorption of metal-halide perovskite nanocrystals (NCs) makes them an ideal candidate for applications which require multiphoton-excited photoluminescence. By doping perovskite NCs with lanthanides, their emission can be extended into the near-infrared (NIR) spectral region. We demonstrate how the combination of Yb3+ doping and bandgap engineering of cesium lead halide perovskite NCs performed by anion exchange (from Cl- to Br-) leads to efficient and tunable emitters that operate under two-photon excitation in the NIR spectral region. By optimizing the anion composition, Yb3+-doped CsPbClxBr3-x NCs exhibited high values of two-photon absorption cross-section reaching 2.3 × 105 GM, and displayed dual-band emission located both in the visible (407-493 nm) and NIR (985 nm). With a view of practical applications of bio-visualisation in the NIR spectral range, these NCs were embedded into silica microspheres which were further wrapped with amphiphilic polymer shells to ensure their water-compatibility. The resulting microspheres with embedded NCs could be easily dispersed in both toluene and water, while still exhibiting a dual-band emission in visible and NIR under both one- and two-photon excitation conditions.

The 12-Membered TNFR1 Peptide, as Well as the 16-Membered and 6-Membered TNF Peptides, Regulate TNFR1-Dependent Cytotoxic Activity of TNF.

Understanding the exact mechanisms of the activation of proinflammatory immune response receptors is very important for the targeted regulation of their functioning. In this work, we were able to identify the sites of the molecules in the proinflammatory cytokine TNF (tumor necrosis factor) and its TNFR1 (tumor necrosis factor receptor 1), which are necessary for the two-stage cytotoxic signal transduction required for tumor cell killing. A 12-membered TNFR1 peptide was identified and synthesized, interacting with the ligands of this receptor protein's TNF and Tag7 and blocking their binding to the receptor. Two TNF cytokine peptides interacting with different sites of TNFR1 receptors were identified and synthesized. It has been demonstrated that the long 16-membered TNF peptide interferes with the binding of TNFR1 ligands to this receptor, and the short 6-membered peptide interacts with the receptor site necessary for the transmission of a cytotoxic signal into the cell after the ligands' interaction with the binding site. This study may help in the development of therapeutic approaches to regulate the activity of the cytokine TNF.

The Impact of SNP-Induced Amino Acid Substitutions L19P and G66R in the dRP-Lyase Domain of Human DNA Polymerase ß on Enzyme Activities.

Base excision repair (BER), which involves the sequential activity of DNA glycosylases, apurinic/apyrimidinic endonucleases, DNA polymerases, and DNA ligases, is one of the enzymatic systems that preserve the integrity of the genome. Normal BER is effective, but due to single-nucleotide polymorphisms (SNPs), the enzymes themselves-whose main function is to identify and eliminate damaged bases-can undergo amino acid changes. One of the enzymes in BER is DNA polymerase ß (Polß), whose function is to fill gaps in DNA. SNPs can significantly affect the catalytic activity of an enzyme by causing an amino acid substitution. In this work, pre-steady-state kinetic analyses and molecular dynamics simulations were used to examine the activity of naturally occurring variants of Polß that have the substitutions L19P and G66R in the dRP-lyase domain. Despite the substantial distance between the dRP-lyase domain and the nucleotidyltransferase active site, it was found that the capacity to form a complex with DNA and with an incoming dNTP is significantly altered by these substitutions. Therefore, the lower activity of the tested polymorphic variants may be associated with a greater number of unrepaired DNA lesions.

Homeotropic orientation of an ion-channel forming mesophase induced by nanotemplate wetting.

Anodic aluminum oxide (AAO) membranes were used as templates to control orientation of an ion-channel forming columnar mesophase obtained by self assembly of a wedge-shaped sulfonate molecule. Inside the AAO structure, the director vector of the mesophase is oriented parallel to the pore axis due to the confinement effect. The molecular arrangement induced by the spatial confinement within the pores is extended over several microns into the remnant film on the AAO surface. The homeotropic alignment of the channels promotes unidimensional ion conduction through the film plane, which is manifested by a considerable increase in conductivity relative to isotropic samples.

A mutation in the cardiac KV7.1 channel possibly disrupts interaction with Yotiao protein.

Here, we characterized the p.Arg583His (R583H) Kv7.1 mutation, identified in two unrelated families suffered from LQT syndrome. This mutation is located in the HС-HD linker of the cytoplasmic portion of the Kv7.1 channel. This linker, together with HD helix are responsible for binding the A-kinase anchoring protein 9 (AKAP9), Yotiao. We studied the electrophysiological characteristics of the mutated channel expressed in CHO-K1 along with KCNE1 subunit and Yotiao protein, using the whole-cell patch-clamp technique. We found that R583H mutation, even at the heterozygous state, impedes IKs activation. Molecular modeling showed that HС and HD helixes of the C-terminal part of Kv7.1 channel are swapped along the C-terminus length of the channel and that R583 position is exposed to the outer surface of HC-HD tandem coiled-coil. Interestingly, the adenylate cyclase activator, forskolin had a smaller effect on the mutant channel comparing with the WT protein, suggesting that R583H mutation may disrupt the interaction of the channel with the adaptor protein Yotiao and, therefore, may impair phosphorylation of the KCNQ1 channel.

EBS in Children with De Novo Pathogenic Variants Disturbing Krt14.

Epidermolysis bullosa simplex (EBS) is a dermatological condition marked by skin fragility and blister formation resulting from separation within the basal layer of the epidermis, which can be attributed to various genetic etiologies. This study presents three pathogenic de novo variants in young children, with clinical manifestations appearing as early as the neonatal period. The variants contribute to the EBS phenotype through two distinct mechanisms: direct keratin abnormalities due to pathogenic variants in the Krt14 gene, and indirect effects via pathogenic mutation in the KLHL24 gene, which interfere with the natural proteasome-mediated degradation pathway of KRT14. We report one severe case of EBS with mottled pigmentation arising from the Met119Thr pathogenic variant in KRT14, another case involving a pathogenic KLHL24 Met1Val variant, and a third case featuring the hot spot mutation Arg125His in KRT14, all manifesting within the first few weeks of life. This research underscores the complexity of genetic influences in EBS and highlights the importance of early genetic screening for accurate diagnosis and management.

Recent advances and fundamentals of microalgae cultivation technology.

Microalgae are considered to be a promising group of organisms for fuel production, waste processing, pharmaceutical applications, and as a source of food components. Unicellular algae are worth being considered because of their capacity to produce comparatively large amounts of lipids, proteins, and vitamins while requiring little room for growth. They can also grow on waste and fix CO2 and nitrogen compounds. However, production costs limit the industrial use of microalgae to the most profitable applications including micronutrient production and fish farming. Therefore, novel microalgae based technologies require an increase of the production efficiencies or values. Here we review the recent studies focused on getting strains with novel characteristics or cultivating techniques that improve production's robustness or efficiency and categorize these findings according to the fundamental factors that determine microalgae growth. Improvements of light and nutrient delivery, as well as other aspects of photobioreactor design, have shown the highest average increase in productivity. Other methods, such as an improvement of phosphorus or CO2 fixation and temperature adaptation have been found to be less effective. Furthermore, interactions with particular bacteria may promote the growth of microalgae, although bacterial and grazer contaminations must be managed to avoid culture failure. The competitiveness of the algal products will increase if these discoveries are applied to industrial settings.