Docetaxel (DTX) is classified as a class IV drug that exhibits poor aqueous solubility (6–7 µg/mL in water) and permeability (P-glycoprotein substrate). The main objective of this study was to construct, characterize, and evaluate docetaxel loaded nanomicellar formulation in vitro for oral delivery to enhance the absorption and bioavailability of DTX, as well as to circumvent P-gp efflux inhibition. Formulations were prepared with two polymeric surfactants, hydrogenated castor oil-40 (HCO-40) and D-α-Tocopherol polyethylene glycol 1000 succinate (VIT E TPGS) with solvent evaporation technique, and the resulting DTX nanomicellar formulations were characterized by proton nuclear magnetic resonance spectroscopy (1H NMR), Fourier Transform Infrared Spectroscopy (FT–IR), X-ray powder diffraction (XRD), and transmission electron microscopy (TEM). Proton NMR, FT–IR, and XRD data indicated that DTX was completely encapsulated within the hydrophobic core of the nanomicelles in its amorphous state. TEM data revealed a smooth spherical shape of the nanomicellar formulation. The optimized formulation (F-2) possessed a mean diameter of 13.42 nm, a zeta potential of −0.19 mV, with a 99.3% entrapment efficiency. Dilution stability study indicated that nanomicelles were stable up to 100-fold dilution with minimal change in size, poly dispersity index (PDI), and zeta potential. In vitro cytotoxicity study revealed higher anticancer activity of DTX nanomicelles at 5 µM compared to the native drug against breast cancer cell line (MCF-7) cells. The LC–MS data confirmed the chemical stability of DTX within the nanomicelles. In vitro drug release study demonstrated faster dissolution of DTX from the nanomicelles compared to the naked drug. Our experimental results exhibit that nanomicelles could be a drug delivery system of choice to encapsulate drugs with low aqueous solubility and permeability that can preserve the stability of the active constituents to provide anticancer activity. Full article

For a sustainable and profitable agriculture production system, balanced and integrated use of nutrients is a key strategy. In addition, partial replacement of chemical fertilizers with organics ones reduces both environmental concerns and economic costs and provides greater soil health benefits. With this hypothesis, an experiment was conducted to assess the yield and economic benefits of a rice-wheat cropping system (RWCS) as influenced by the joint application of sewage sludge (SSL) and fertilizer. The treatments comprised: without fertilizer or SSL; 100% recommended dose of fertilizers (RDF); 100% RDF + 20 Mg ha⁻¹ SSL; 100% RDF + 30 Mg ha⁻¹ SSL; 50% RDF + 20 Mg ha⁻¹ SSL; 60% RDF + 20 Mg ha⁻¹ SSL; 70% RDF + 20 Mg ha⁻¹ SSL; 50% RDF + 30 Mg ha⁻¹ SSL; 60% RDF + 30 Mg ha⁻¹ SSL and 70% RDF + 30 Mg ha⁻¹ SSL. The experiment was laid out in a randomized block design with three replications. The result of our study indicate that the highest percent increase in mean plant height i.e., ~14.85 and ~13.90, and grain yield i.e., ~8.10 and ~18.90 for rice and wheat, respectively, were recorded under 100% RDF + 30 Mg SSL ha⁻¹ treatment compared to 100% RDF, while 70% RDF + 20 Mg ha⁻¹ SSL produced a statistically equivalent grain yield of 100% RDF in RWCS. The application of 20 and 30 Mg SSL ha⁻¹ along with recommended or reduced fertilizer dose, significantly increased the heavy metal content in plant and soil systems above that of 100% RDF, but this enhancement was found within permissible limits. Moreover, the reduced use of SSL i.e., 20 Mg SSL ha⁻¹, resulted in lower heavy metal content in grain and soil than did the 30 Mg ha⁻¹ SSL treatment, but significantly higher than in the absolute control or 100% RDF treatment. In summary, the use of 20 Mg ha⁻¹ SSL along with 70% RDF provided a safer, profitable and sustainable option in a rice-wheat cropping system in the middle Ganegatic alluvial plain. Full article

This study was a multicenter retrospective cohort study of term nulliparous women who underwent labor, and was conducted to develop an automated machine learning model for prediction of emergent cesarean section (CS) before onset of labor. Nine machine learning methods of logistic regression, random forest, Support Vector Machine (SVM), gradient boosting, extreme gradient boosting (XGBoost), light gradient boosting machine (LGBM), k-nearest neighbors (KNN), Voting, and Stacking were applied and compared for prediction of emergent CS during active labor. External validation was performed using a nationwide multicenter dataset for Korean fetal growth. A total of 6549 term nulliparous women was included in the analysis, and the emergent CS rate was 16.1%. The C-statistics values for KNN, Voting, XGBoost, Stacking, gradient boosting, random forest, LGBM, logistic regression, and SVM were 0.6, 0.69, 0.64, 0.59, 0.66, 0.68, 0.68, 0.7, and 0.69, respectively. The logistic regression model showed the best predictive performance with an accuracy of 0.78. The machine learning model identified nine significant variables of maternal age, height, weight at pre-pregnancy, pregnancy-associated hypertension, gestational age, and fetal sonographic findings. The C-statistic value for the logistic regression machine learning model in the external validation set (1391 term nulliparous women) was 0.69, with an overall accuracy of 0.68, a specificity of 0.83, and a sensitivity of 0.41. Machine learning algorithms with clinical and sonographic parameters at near term could be useful tools to predict individual risk of emergent CS during active labor in nulliparous women. Full article

The purpose of this pilot study was to explore whether polymorphisms in genes encoding the catalytic (GCLC) and modifier (GCLM) subunits of glutamate-cysteine ligase, a rate-limiting enzyme in glutathione synthesis, play a role in the development of ischemic stroke (IS) and the extent of brain damage. A total of 1288 unrelated Russians, including 600 IS patients and 688 age- and sex-matched healthy subjects, were enrolled for the study. Nine common single nucleotide polymorphisms (SNPs) of the GCLC and GCLM genes were genotyped using the MassArray-4 system. SNP rs2301022 of GCLM was strongly associated with a decreased risk of ischemic stroke regardless of sex and age (OR = 0.39, 95%CI 0.24–0.62, p < 0.0001). Two common haplotypes of GCLM possessed protective effects against ischemic stroke risk (p < 0.01), but exclusively in nonsmoker patients. Infarct size was increased by polymorphisms rs636933 and rs761142 of GCLC. The mbmdr method enabled identifying epistatic interactions of GCLC and GCLM gene polymorphisms with known IS susceptibility genes that, along with environmental risk factors, jointly contribute to the disease risk and brain infarct size. Understanding the impact of genes and environmental factors on glutathione metabolism will allow the development of effective strategies for the treatment of ischemic stroke and disease prevention. Full article

Screening microalgae from extreme environments, including hot springs, is an important research topic that has lately emerged. A thermophilic green alga was isolated from a north-eastern Algerian hot spring at a temperature of 63 °C, and its fatty acid (FA) profile was explored. The strain was cultivated in BBM medium at 35 °C in a 16:8 h light/dark cycle and 75 μM photons m⁻² s⁻¹. The morphological studies combined with phylogenetic analysis revealed that the isolate was Coelastrella thermophila var. globulina Q. Wang, H. Song, X. Liu, G. Liu and Z. Hu. The monounsaturated fatty acid (MUFA) content was 51.12%. The saturated fatty acid (SFA) and polyunsaturated fatty acid (PUFA) content, respectively, accounted for 27.01% and 21.87%. The main FA was oleic acid (18:1n–9), whose value was 35.95%, followed in decreasing order by palmitic acid (16:0) with 21.45%, linoleic acid (18:2n–6) with 14.38% and α-linolenic acid (18:3n–3) with 04.22%. The FA profile exhibited high total n–6 and n–3 PUFA values (15.80% and 5.76%, respectively). Coelastrella thermophila var. globulina is particularly interesting for producing n-6 and n-3 PUFA and is likely suitable for other biotechnological purposes. This is the first time that this taxon has been reported in hot springs. Other species can be expected to be reported, which emphasises the importance of the biodiversity of extreme habitats. Full article

Ankyloglossia, commonly known as tongue-tie, is the most common disorder of tongue morphology characterized by aberrant attachment of the lingual frenum. This study aimed to provide a comprehensive literature review and evaluate the effectiveness of various laser wavelengths in the surgical treatment of patients with ankyloglossia. An electronic screening of PubMed and the Cochrane Central Register of Controlled Trials (CENTRAL) databases was conducted on 8 November 2021. The following search terms were used to review the available data on the subject of interest: (ankyloglossia OR tongue tie OR short lingual frenulum OR lingual frenectomy OR lingual frenulectomy OR lingual frenotomy OR lingual frenulotomy) AND laser. The use of lasers in ankyloglossia treatment resulted in shorter procedure time, reduced indications for general anesthesia, reduced administration of postoperative analgesics, fewer sutures or none needed, reduced postoperative bleeding, and improved healing. Despite many advantages, this method has its clinical limitations: it requires the use of expensive equipment; well-trained personnel familiar with lasers; and personal protective equipment for the patient, caregiver, operator, and assistant. The laser procedure does not eliminate the need for myofunctional exercises and work with a speech therapist. Full article

Introduction: Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy. This meta-analysis compared local steroid injections (LSIs) versus carpal tunnel release (CTR) for the management of CTS. Neurophysiological parameters, patient-reported outcome measures (PROMs), and the complication rate were investigated. We hypothesized that LSIs may represent an effective and safe alternative to surgical management. Methods: This systematic review was conducted according to the 2020 PRISMA statement. All the clinical investigations comparing LSIs versus CTR for carpal tunnel syndrome were accessed. In March 2022, the following databases were accessed: Pubmed, Web of Science, Google Scholar, and Embase. No time constrains were used for the search. The risk of bias and statistical analyses were conducted using the Review Manager Software 5.3 (The Nordic Cochrane Collaboration, Copenhagen). Results: Data from 1096 procedures were retrieved. The mean follow-up was 12.3 (1 to 58) months. The mean age of the patients was 51.1 ± 4.6. Nocturnal paraesthesia (p < 0.0001) and visual analogue scale (p < 0.0001) were greater in the LSIs cohort. No difference was found in the functional (p = 0.2) and symptom (p = 0.4) subscales of the Boston Carpal Tunnel Questionnaire (BCTQ), median nerve distal motor latency (p = 0.9), median nerve motor amplitude (p = 0.7), median nerve sensory conduction velocity (p = 0.4), or median nerve sensory amplitude (p = 0.3). No difference was found in terms of minor complications (p = 0.9). No major complications were observed within the duration of follow-up. Conclusion: Both CTR and LSIs were effective and feasible in reducing symptoms of carpal tunnel syndrome. Though LSIs led to greater pain relief, this superiority was not permanent. Irrespective of the severity of the symptoms, current evidence suggests that a cycle of LSIs may be considered in patients with CTS. However, patients must be aware that LSIs may not be the definitive therapy, and CTR should be recommended. Full article

Adoptive cell therapy with genetically modified T lymphocytes that express chimeric antigen receptors (CAR-T) is one of the most promising advanced therapies for the treatment of cancer, with unprecedented outcomes in hematological malignancies. However, the efficacy of CAR-T cells in solid tumors is still very unsatisfactory, because of the strong immunosuppressive tumor microenvironment that hinders immune responses. The development of next-generation personalized CAR-T cells against solid tumors is a clinical necessity. The identification of therapeutic targets for new CAR-T therapies to increase the efficacy, survival, persistence, and safety in solid tumors remains a critical frontier in cancer immunotherapy. Here, we summarize basic, translational, and clinical results of CAR-T cell immunotherapies in lung cancer, from their molecular engineering and mechanistic studies to preclinical and clinical development. Full article

Canine mammary cancer (CMC), similar to human breast cancer (HBC) in many aspects, is the most common neoplasm associated with significant mortality in female dogs. Due to the limited therapy options, biomarkers are highly desirable for early clinical diagnosis or cancer progression monitoring. Since the discovery of microRNAs (miRNAs or miRs) as post-transcriptional gene regulators, they have become attractive biomarkers in oncological research. Except for intracellular miRNAs and cell-free miRNAs, exosome-derived miRNAs (exomiRs) have drawn much attention in recent years as biomarkers for cancer detection. Analysis of exosomes represents a non-invasive, pain-free, time- and money-saving alternative to conventional tissue biopsy. The purpose of this review is to provide a summary of miRNAs that come from non-exosomal sources (canine mammary tumor, mammary tumor cell lines or canine blood serum) and from exosomes as promising biomarkers of CMC based on the current literature. As is discussed, some of the miRNAs postulated as diagnostic or prognostic biomarkers in CMC were also altered in HBC (such as miR-21, miR-29b, miR-141, miR-429, miR-200c, miR-497, miR-210, miR-96, miR-18a, miR19b, miR-20b, miR-93, miR-101, miR-105a, miR-130a, miR-200c, miR-340, miR-486), which may be considered as potential disease-specific biomarkers in both CMC and HBC. Full article

In this review, we describe the creation of the Nucleic Acid Database (NDB) at Rutgers University and how it became a testbed for the current infrastructure of the RCSB Protein Data Bank. We describe some of the special features of the NDB and how it has been used to enable research. Plans for the next phase as the Nucleic Acid Knowledgebase (NAKB) are summarized. Full article

Transposable elements (TEs) comprise a substantial portion of eukaryotic genomes. They have the unique ability to integrate into new locations and serve as the main source of genomic novelties by mediating chromosomal rearrangements and regulating portions of functional genes. Recent studies have revealed that TEs are abundant in sex chromosomes. In this review, we propose evolutionary relationships between specific TEs, such as Ty3/Gypsy, and sex chromosomes in different lineages based on the hypothesis that these elements contributed to sex chromosome differentiation processes. We highlight how TEs can drive the dynamics of sex-determining regions via suppression recombination under a selective force to affect the organization and structural evolution of sex chromosomes. The abundance of TEs in the sex-determining regions originates from TE-poor genomic regions, suggesting a link between TE accumulation and the emergence of the sex-determining regions. TEs are generally considered to be a hallmark of chromosome degeneration. Finally, we outline recent approaches to identify TEs and study their sex-related roles and effects in the differentiation and evolution of sex chromosomes. Full article

Spodoptera frugiperda (fall armyworm) is a member of the superfamily Noctuoidea that accounts for more than a third of all Lepidoptera and includes a considerable number of agricultural and forest pest species. Spodoptera frugiperda is a polyphagous species that is a significant agricultural pest worldwide, emphasizing its economic importance. Spodoptera frugiperda’s genome size, assembly, phylogenetic classification, and transcriptome analysis have all been previously described. However, the different studies reported different compositions of repeated DNA sequences that occupied the whole assembled genome, and the Spodoptera frugiperda genome also lacks the comprehensive study of dynamic satellite DNA. We conducted a comparative analysis of repetitive DNA across geographically distant populations of Spodoptera frugiperda, particularly satellite DNA, using publicly accessible raw genome data from eight different geographical regions. Our results showed that most transposable elements (TEs) were commonly shared across all geographically distant samples, except for the Maverick and PIF/Harbinger elements, which have divergent repeat copies. The TEs age analysis revealed that most TEs families consist of young copies 1–15 million years old; however, PIF/Harbinger has some older/degenerated copies of 30–35 million years old. A total of seven satellite DNA families were discovered, accounting for approximately 0.65% of the entire genome of the Spodoptera frugiperda fall armyworm. The repeat profiling analysis of satellite DNA families revealed differential read depth coverage or copy numbers. The satellite DNA families range in size from the lowest 108 bp SfrSat06-108 families to the largest (1824 bp) SfrSat07-1824 family. We did not observe a statistically significant correlation between monomer length and K2P divergence, copy number, or abundance of each satellite family. Our findings suggest that the satellite DNA families identified in Spodoptera frugiperda account for a considerable proportion of the genome’s repetitive fraction. The satellite DNA families’ repeat profiling revealed a point mutation along the reference sequences. Limited TEs differentiation exists among geographically distant populations of Spodoptera frugiperda. Full article

The incidence of autoimmune bullous disorders has increased over the years, especially in elderly patients with multiple comorbidities, which has stimulated research into their association with other diseases. We performed a retrospective observational study used the Minimum Basic Data Set of hospital discharges to review records of patients admitted to Spanish public hospitals between 2016 and 2019 with a diagnosis of any autoimmune bullous disorder. The objectives were to describe the comorbidity profile and the clinical-epidemiological characteristics of patients with pemphigus and pemphigoid, and analyze the evolution of the incidence of these diseases. The study included 1950 patients with pemphigus and 5424 patients with pemphigoid. Incidence increased from 2016 to 2019. The main comorbidities were hypertension (40.19%) and diabetes mellitus (28.57%). Compared to patients with pemphigoid, those with pemphigus had a higher prevalence of neoplasms, osteoporosis, solid metastases and malignant lymphoma, while the prevalence of hypertension, kidney disease, diabetes, heart failure, dementia, chronic obstructive pulmonary disease and Parkinson’s disease was higher in the pemphigoid group (p < 0.05). Therefore, since autoimmune bullous disorders are associated with diverse comorbidities and their incidence has risen in recent years, the establishment of strategies to prevent the main comorbidities in these patients is justified. Full article

The RNA world is one of the principal hypotheses to explain the emergence of living systems on the prebiotic Earth. It posits that RNA oligonucleotides acted as both carriers of information as well as catalytic molecules, promoting their own replication. However, it does not explain the origin of the catalytic RNA molecules. How could the transition from a pre-RNA to an RNA world occur? A starting point to answer this question is to analyze the dynamics in sequence space on the lowest level, where mononucleotide and short oligonucleotides come together and collectively evolve into larger molecules. To this end, we study the sequence-dependent self-assembly of polymers from a random initial pool of short building blocks via templated ligation. Templated ligation requires two strands that are hybridized adjacently on a third strand. The thermodynamic stability of such a configuration crucially depends on the sequence context and, therefore, significantly influences the ligation probability. However, the sequence context also has a kinetic effect, since non-complementary nucleotide pairs in the vicinity of the ligation site stall the ligation reaction. These sequence-dependent thermodynamic and kinetic effects are explicitly included in our stochastic model. Using this model, we investigate the system-level dynamics inside a non-equilibrium ‘RNA reactor’ enabling a fast chemical activation of the termini of interacting oligomers. Moreover, the RNA reactor subjects the oligomer pool to periodic temperature changes inducing the reshuffling of the system. The binding stability of strands typically grows with the number of complementary nucleotides forming the hybridization site. While shorter strands unbind spontaneously during the cold phase, larger complexes only disassemble during the temperature peaks. Inside the RNA reactor, strand growth is balanced by cleavage via hydrolysis, such that the oligomer pool eventually reaches a non-equilibrium stationary state characterized by its length and sequence distribution. How do motif-dependent energy and stalling parameters affect the sequence composition of the pool of long strands? As a critical factor for self-enhancing sequence selection, we identify kinetic stalling due to non-complementary base pairs at the ligation site. Kinetic stalling enables cascades of self-amplification that result in a strong reduction of occupied states in sequence space. Moreover, we discuss the significance of the symmetry breaking for the transition from a pre-RNA to an RNA world. Full article

Inflammation is the preceding condition for the development of mild and severe pathological conditions, including various forms of osteopenia, cancer, metabolic syndromes, neurological disorders, atherosclerosis, cardiovascular, lung diseases, etc., in human and animals. The inflammatory status is induced by multifarious intracellular signaling cascades, where cytokines, chemokines, arachidonic acid metabolites, adhesion molecules, immune cells and other components foster a “slow burn” at a local or systemic level. Assuming that countering inflammation limits the development of inflammation-based diseases, a series of new side-effects-free therapies was assessed in experimental and domestic animals. Within the targets of the drug candidates for quenching inflammation, an archetypal autophagic gear, the p62/sqstm1 protein, has currently earned attention from researchers. Intracellular p62 has been recently coined as a multi-task tool associated with autophagy, bone remodeling, bone marrow integrity, cancer progression, and the maintenance of systemic homeostasis. Accordingly, p62 can act as an effective suppressor of inflamm-aging, reducing oxidative stress and proinflammatory signals. Such an operational schedule renders this protein an effective watchdog for degenerative diseases and cancer development in laboratory and pet animals. This review summarizes the current findings concerning p62 activities as a molecular hub for cell and tissues metabolism and in a variety of inflammatory diseases and other pathological conditions. It also specifically addresses the applications of exogenous p62 (DNA plasmid) as an anti-inflammatory and homeostatic regulator in the treatment of osteoporosis, metabolic syndrome, age-related macular degeneration and cancer in animals, and the possible application of p62 plasmid in other inflammation-associated diseases. Full article