As critical biocontrol agents, Trichoderma and Metarhizium have demonstrated vast potential in disease prevention and pest control respectively. Current applications, however, are predominantly confined to singular use or simplistic combinations of the two fungi. This study innovatively utilizes Metarhizium and Trichoderma as experimental subjects, employing non-targeted metabolomics to compare the differences in metabolites between co-culture and separate fermentation. The metabolite distinctions in co-culture are meticulously analyzed using sample correlation, least squares discriminant analysis, cluster analysis, and KEGG enrichment analysis. Metabolome sequencing analysis is then applied to compare the co-culture fermentation filtrate with Trichoderma atroviride and Metarhizium anisopliae. Differential metabolite analysis found that co-culture had significantly up-regulated or down-regulated metabolites compared to singular cultures.However,significant metabolite discrepancies are discovered in singular cultures, notably the up-regulated metabolites such as osthole and spirocyclic amine, which have documented antibacterial functions that may prove effective against Fusarium graminearum. Ultimately, the findings from this research contribute to the exploration of synergistic applications of biocontrol fungi and serve as a valuable reference for future development of bio-pesticides for disease and pest control.

Inflammation is implicated in the etiology of obesity-related diseases. Thromboxane-prostanoid receptor (TPR) is known to play a role in mediating an inflammatory response in a variety of cells. Gut-derived lipopolysaccharide (LPS), a TLR4 agonist, is elevated in obesity. Moreover, free fatty acids (FFAs) are important mediators of obesity-related inflammation. However, the role and mechanisms by which TPR regulates the inflammatory response in human immune cells remain unclear. We sought to determine the link between TPR and obesity and the role/mechanisms by which TPR alters LPS or stearic acid (SA)-induced inflammatory response in PBMCs. Cells were pre-treated with agents blocking TPR signaling, followed by treatment with LPS or stearic acid (SA). Our findings showed that TPR mRNA levels are higher in PBMCs from individuals with obesity. Blockade of TPR as well as ROCK which acts downstream of TPR, attenuated LPS and/or SA-induced pro-inflammatory response. On the other hand, TPR activation using its agonist enhanced the pro-inflammatory effects of LPS and/or SA. Of note, TPR agonist by itself elicits an inflammatory response which was attenuated by blocking TPR or ROCK. Our data suggest that TPR plays a key role in promoting an inflammatory response in human PBMCs and this effect is mediated via TLR4 and/or ROCK signaling.

Cancer treatment is a significant focus in medicine owing to the increasing global incidence. Patients with advanced cancers that do not respond to conventional therapies have limited options and an unfavorable prognosis. Consequently, researchers are investigating complementary approaches to conventional treatments. One such approach is alkalization therapy, which aims to neutralize the acidic tumor microenvironment (TME) by increasing its pH level. The acidic TME promotes inflammation, tumor progression, and drug resistance. Alkalization therapy has been demonstrated to be effective for various cancers. In addition, natural products, such as triterpenoids, parthenolides, fulvic acid, Taxus yunnanensis, and apple pectin have the potential to alleviate symptoms, maintain physical fitness, and improve treatment outcomes of cancer patients through their anti-inflammatory, antioxidant, and anticancer properties. In this review, we focus on the effects of alkalization therapy and natural products on cancer. Furthermore, we present a case series of advanced cancer patients who received alkalization therapy and natural products alongside standard treatments, resulting in long-term survival. We posit that alkalization therapy together with the supplementation of natural products may confer benefits to cancer patients by mitigating the side effects of chemotherapy and complementing standard treatments. However, further research is warranted to validate these clinical findings.

Correlations among estrus cycle, pyometra, and canine diabetes mellitus (CDM) have been described since the late 1950s, and substantial progress in understanding mechanisms beyond was achieved nowadays. Progesterone-related diabetes mellitus (PRDM) in dogs is known for its particular potential for diabetes remission. Thus, a deep understanding of the physiopathological aspects involved is crucial to postulate treatment guidelines to improve the PRDM remission rate, as well as to inform preventive measures. This narrative review aims to provide relevant detailed information on 1) canine estrus cycle and its impact on CDM etiology and management, 2) the role of pyometra as a further cause of insulin resistance, and 3) useful individual therapeutic and preventive strategies. Pharmacological annulment of progesterone effects, as well as inflammatory and progesterone-related conditions resolution in association with adequate exogenous insulin therapy, and residual beta cell function, are key aspects to achieve remission, or at least to improve diabetic clinical control. In this way, spaying should be considered mandatory in most PRDM cases. Preventive measures against CDM can include spaying recommendations; however, individual-based recommendations should be considered since castration may be associated with some long-term health issues.

Introduction/Aim: Central sensitivity to thyroid hormones refers to the sensitivity of the hypothalamic-pituitary-thyroid (HPT) axis to changes in circulating free thyroxine (fT4). The relationship between fT4 levels and iodine intake is complex. The aim of the present study was to assess central sensitivity to thyroid hormones in pregnancy against iodine intake. Materials & Methods: One thousand one hundred two blood and urine samples were collected from pregnant women (with a mean age+SD of 30.4+4.6 years) during singleton pregnancies; women with known/diagnosed thyroid disease were excluded. Specifically, TSH & fT4 and 24-hour urinary iodine excretion (UI) were measured in each trimester and at two months postpartum. The Thyroid Feedback Quantile-based Index (TFQI) was calculated to assess central sensitivity to thyroid hormones. For the statistical analysis of TFQI by time period, analysis of variance (ANOVA) was used, while Pearson's correlation was used to assess TFQI versus UI. Results: The mean TFQI index ranged from -0.06 (first trimester) to -0.07 (two months postpartum), while the corresponding UI was 141 and 172 μg/L, respectively. The TFQI-UI correlation was negative (Pearson r: -0.325, p: 0.04 and r: -0.399, p: 0.023), for UI values over 250 μg/L, in the first and the third trimester of pregnancy, respectively. Discussion: TFQI is a new index reflecting central sensitivity to thyroid hormones. Lower TFQI indicates higher sensitivity to thyroid hormones. In our sample TFQI was inversely related to iodine intake, in the first trimester of pregnancy (the critical period of organogenesis) and the third trimester (the critical period of fetal growth). Thus, the observed changes in TFQI may reflect different ways of central action of thyroid hormones, according to the phase of pregnancy. The negative association between maternal TFQI (indicative of central sensitivity to thyroid hormone) and urine iodine levels during the third trimester of pregnancy may reflect the combined influence of maternal and fetal thyroid function. Our results are intriguing and have the potential to enhance our comprehension of the changes in the HPT axis’ function via variations in central sensitivity to thyroid hormones and its interplay with nutritional iodine status during pregnancy.

Laurencia seaweed species synthesize a broad range of secondary metabolites mainly terpenes, such as the elatol exhibiting ecological roles, such as defense against fouling and herbivores. Recently, an intricate cellular machinery was evidenced concerning terpenes biosynthetic pathways, storage inside corps en cerise - CC and regulated exocytosis in these species. But for seaweeds in general, the proteins involved in transmembrane transport of secondary metabolites remains unknown. Assays with Rhodamine-123 and cyclosporine A (CSA) revealed the presence of ABC transporters in CC membrane of Laurencia dendroidea. In vivo incubation assays with CSA resulted in CC morphological changes, reduced intracellular elatol concentrations and increased biofouling cover on the seaweed surface. Cultivation assays in the presence of a marine pathogenic bacteria induced the expression of ABC proteins belonging to the subfamilies ABCB, ABCD, ABCF and ABCG. The later subfamily is known to associated in the transport terpenes in plants. Our results shed new light on the role of ABC proteins in key mechanisms of the defensive system in seaweeds against fouling and herbivory.

Various symptoms have been reported to persist beyond acute phase of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which is referred as long coronavirus disease 19 (long COVID-19). Over 65 million individuals suffer from long COVID-19. However, the causes of long COVID-19 have been largely unknown. Since long COVID-19 symptoms are observed throughout the body, vascular endothelial dysfunction may be a strong candidate to induce long COVID-19. The angioten-sin-converting enzyme 2 (ACE2), the entry receptor of SARS-CoV-2, is ubiquitously expressed in endothelial cells. We previously found that the risk factors for athero-sclerotic cardiovascular disease (ASCVD) and the history of ASCVD can be the risk for severe COVID-19, suggesting a contribution of pre-existing endothelial dysfunction to severe COVID-19. Here, we show a significant association of endothelial dysfunction with development of long COVID-19 and show that biomarkers for endothelial dysfunction in patients with long COVID-19 are also crucial players in development of ASCVD. We consider the influence of long COVID-19 on development of chronic kidney disease (CKD) and ASCVD. Furthermore, we suggest the therapeutic interventions for long COVID-19 by considering endothelial dysfunction as the treatment tar-gets for long COVID-19. Such interventions may prevent pandemic of CKD and ASCVD in post COVID-19 era.

The solute carrier family 25 (SLC25) participates in the transport of metabolites and cofactors across the membranes of mitochondria, plastids, peroxisomes, and endoplasmic reticulum. By calling for genomic blocks involved in adjacent metabolic reactions, this report introduces gene clusters of the Slc25 subfamily 44, stilbene and chalcone synthases, and subunits of the mitochondrial electron transfer complexes. The Slc25A44 gene was found ubiquitously expressed and transcriptionally co-regulated with energy metabolism genes in human, mouse, and Arabidopsis thaliana. The Slc25A44s also had no homozygous missense mutation and were highly conserved at intra-species level with the majority of polymorphism present in the non-coding regions. When expressed in oocytes, AdSlc25A44 from Arachis duranensis showed transport activity for the common precursors of flavonoids, stilbenoids, and ubiquinone. Accordingly, AdSLC25A44 and its human orthologue HsSLC25A44 elevated the production of para-coumaric, 4-aminobenzoic, and 4-hydroxybenzoic acids in Saccharomyces cerevisiae strains designed to produce para-coumaric acid via different pathways. Moreover, the engineered SLC25 subfamily specific signature, i.e., AdSLC25A44^LWW206IQF, had a stronger effect on para-coumaric acid secretion than the native variant. Importantly, the aerobic growth-rate of S. cerevisiae was significantly higher when expressing the AdSLC25A44, HsSLC25A44, or AdSLC25A44^LWW206IQF. These results suggest that SLC25A44 is an essential mitochondrion-ER-nucleus zone transporter associated with metabolism of secondary metabolites and energy.

Childhood obesity is a public health problem and most of the interventions are focused on healthy habits as reducing energy intake, avoiding a sedentary lifestyle and increasing physical activity. However, usually they are based in individual programs, with few structured interventions in health systems without satisfactory results. PinPo aims to carry out an integral intervention in children with obesity, as well as in their parents and caregivers, to get motivation to change towards healthy lifestyle habits. The program contains 9 educational grupal sessions directed by a multidisciplinary expert team. 10 boys and girls, and another group with 10 family members and/or caregivers participate in sessions during 90 min biweekly. Moreover, there is an individual adaptation depending on the severity and comorbidities. At the beginning and at the end of the program, an integral evaluation for health status is developed including anthropometric, nutritional, physical activity, and psychologist and analytical measurements. Finally, a satisfaction survey is carried out on the participants.In conclusion, the implementation of PinPo could offer to paediatric patients with obesity and their families, an integral intervention to treat obesity and its complications. So, there are expectations of achieving favorable results that also allow to optimize its effectiveness.

The stromal vascular cell fraction (SVF) of visceral and subcutaneous adipose tissue (VAT and SAT) has increasingly come into focus in stem cell research, since these compartments represent a rich source of multipotent adipose-derived stem cells (ASCs). ASCs exhibit a self- renewal potential and differentiation capacity. Our aim was to study the different expression of embryonic stem cell markers NANOG, SOX2 and OCT3/4 and to evaluate if there exists a hierarchal role in this network in ASCs derived from both SAT and VAT. ASCs were isolated from SAT and VAT biopsies of 72 consenting patients (23 men, 47 women; age 45 ± 10; BMI between 25 and 30 range) undergoing elective open-abdominal surgery. Sphere-forming capability was evaluated by plating cells in low adhesion plastic. Stem cell markers CD90 and CD105 were analyzed by flow cytometry and stem cell transcription factors NANOG, SOX2 and OCT3/4 were detected by immunoblotting and Real-Time PCR. NANOG, SOX2 and OCT3/4 interplay was explored by gene silencing. ASCs from VAT and SAT confirmed their mesenchymal stem cell (MSC) phenotype expressing the specific MSC markers CD90, CD105, NANOG, SOX2 and OCT3/4. NANOG silencing induced a significant OCT 3/4 (70% ± 0.05) and SOX2 (75% ± 0.03) down-regulation whereas SOX2 silencing did not affect NANOG gene expression. Adipose tissue is an important source of MSC, and siRNA experiments endorse a hierarchical role of NANOG in the complex transcription network that regulates pluripotency and plasticity.

Dengue virus is a global health problem most prevalent in tropical and subtropical regions. However, after the approval of two vaccines, Dengvaxia, TV003/TV005 of Takeda, for its prevention, problems were reported, like enhanced risks of infection or less efficiency of protection. Since then, more struggles have been in demand for the development of better vaccines. Here, we conducted a new design through an in-silico strategy. Initially, epitopes were chosen based on their antigenicity, immunogenicity, and binding affinity with MHC molecule, while excluded with allergenicity, toxicity and potential risk of antibody dependent enhancement. Subsequently, a core antigen was constructed with selected epitopes and linked with distinct adjuvant proteins to achieve three candidate vaccines, PSDV-1~3. PSDV-2 was chosen for further validation based on their advantage in physicochemical and structural properties. With a panel of simulations, this artificial protein showed tight binding with pattern recognition receptors, good stability, robust immune induction, and ultimately was confirmed as a high quality vaccine candidate. The plasmid for its recombinant expression was then designed accordingly. With our new design, one more choice was obtained for the effective protection from Dengue virus. Further experimental validations are still require to confirm it protection capacity and safety.

Senna rugosa is a species found in the Cerrado and used in folk medicine as a vermifuge and in the treatment of poisonous snakebites accidents. In this work, we identified the main secondary metabolites present in ethanolic extracts of the leaves (ELSR) and roots (ERSR) of S. rugosa and evaluated the potential cytoprotective effect against cellular macromolecular damage, as well as the cytotoxic properties of the extracts on the K562 and Jurkat leukemic cell lines. The identification of metabolites was done by liquid chromatography coupled with mass spectrometry. The antioxidant activities were investigated by direct ABTS•+ and DPPH• radical scavenging methods, protection against oxidative damage in proteins and DNA. The cytotoxic properties were investigated against healthy cells, isolated from human peripheral blood (PBMC) and leukemic cell lines. The leaf extract contains catechin, rutin, epigallocatechin derivatives, kaempferol glycosides, luteolin, and dimeric and trimeric procyanidins, while the root extract profile shows obtusichromoneside derivatives, 2-methoxystypandrone, stilbene derivatives, naphthopyranones, and flavanone derivatives. The extracts showed antioxidant activity, with IC50 of 4.86 ± 0.51 µg/mL and 8.33 ± 0.90 µg/mL in the ABTS assay for ELSR and ERSR, respectively. And in the DPPH• assay, the IC50 was 19.98 ± 1.96 µg/mL for ELSR and 13.37 ± 1.05 µg/mL for ERSR. The extracts protected macromolecules against oxidative damage at concentrations of 5 µg/mL. The cytotoxicity test against leukemic strains was observed after 24 and 48 hours of treatment. After 48 h, results against the K562 cell line demonstrate IC50 of 242.54 ± 2.38 µg/mL and 223.00 ± 2.34 µg/mL for ELSR and ERSR , respectively. While against the Jurkat cell line, these extracts showed IC50 of 171.45 ± 2.25 µg/mL and 189.30 ± 2.27 µg/mL, respectively Results on PBMC viability, demonstrate that the extracts showed selectivity for the leukemic cell lines. Together, our results reveal that the leaves and roots of S. rugosa have completely distinct and complex chemical compositions. This study expands the repertoire of identified chemical compounds and underscores their significant pharmacological potential in conditions related to oxidative stress and leukemia.

Background and Objectives: To investigate the relationship between the SII index and the micro-macro complications and death that develop in the first year and the following 3 years, following the calculation of the index in type 2 diabetic retinopathy patients. Materials and Methods: This study was performed retrospectively with 523 type 2 diabetic retinopathy patients admitted to the endocrinology outpatient clinic of our hospital between January 2019 and December 2019. The demographic, and clinical characteristics of the patients were evaluated using descriptive statistics. Shapiro-Wilk test was used for the normal distribution of quantitative data; Mann-Whitney U, Mc Nemar Chi-square, and Cochran's Q tests were used to analyze SII values between groups and complication rates by years; sensitivity and specificity were determined by ROC analysis and considered statistically significant with a significance level of P

The double burden of malnutrition (DBM) is escalating in low- and middle-income countries (LMICs), including in Rwanda, most notably in urbanizing areas. The 2019-2020 Rwanda Demographic Health Survey (DHS) revealed 33% of children under 5 are stunted while 42% of women in urban areas are overweight or obese. This coexistence has contributed to a surge in non-communicable diseases (NCDs), particularly in secondary cities. Using the World Health Organization’s (WHOs) “double-duty action” (DDA) concept, this study aims to identify and evaluate interventions with double-duty potential in Rwanda, focusing on the districts of Rusizi and Rubavu. Guided by Hawkes et al.’s conceptual framework for identifying DDA entry points, a desk review of national policies pinpointed 4 programs with DDA potential: early childhood development (ECD) centers, the school feeding program, farmer field schools (FFS), and the provision of nutrition-sensitive direct support. In-person interviews with key stakeholders assessed their implementation and a Strengths, Weaknesses, Opportunities, and Threats (SWOT) analysis informed context-specific recommendations for their improvement. Recommendations include targeting beliefs surrounding nutrition, improving trainings for community educators, enhancing parent – particularly father – involvement, and close follow-up. These findings offer actionable strategies for governments and nutrition stakeholders and may benefit similar interventions in other rapidly urbanizing LMICs.

Energy metabolism regulates the proliferation of stem cells by regulating energy production and the production of substrates through biosynthetic pathways. It is an important target for cell regulation and stem cell applications, and is crucial for determining the pluripotency and cell fate of stem cells. In this context, this article focuses on reviewing the latest research progress on the association between glucose metabolism, amino acid metabolism, fatty acid metabolism, and mitophagy with stem cell function, elucidating how key energy metabolism pathways affect stem cell function by regulating signal transduction and epigenetic modifications. In this review, we discuss the key factors affecting energy metabolism and their association with stem cell function. The integration of energy metabolism and stem cell fate regulation will open up a new path for future regenerative medicine practices.

Many risk-modifying factors affect cancer incidence and mortality rates. We present an ecological study of incidence and/or mortality rates for cancers during 2007–2016 of 17 anatomical sites with respect to solar ultraviolet-B (UVB) doses and obesity prevalence. Solar UVB reduces cancer risk by producing vitamin D, which has many mechanisms to reduce risk of cancer incidence, progression, and metastasis. Obesity increases cancer risk through several mechanisms, including increased systemic inflammation. Data were averaged for 12 geographical regions. Solar UVB doses were significantly inversely correlated with mortality rates for five cancers for males and four for females. Obesity prevalence was directly correlated with mortality rates for three cancers for males and seven for females. The population attributable fraction of cancer mortality rates ascribed to low solar UVB dose was 0.03 for both males and females, whereas that for obesity prevalence was 0.05 for males and 0.08 for females. Thus, cancer mortality rates in France could be reduced through vitamin D supplementation and reducing the prevalence of obesity. Doing so also could reduce risk of other adverse health outcomes.

Curcumin, a polyphenol with a rich history spanning two centuries, has emerged as a promising therapeutic agent targeting multiple signaling pathways and exhibiting cellular-level activities that contribute to its diverse health benefits. Extensive preclinical and clinical studies have demonstrated its ability to enhance the therapeutic potential of various bioactive compounds. While its reported therapeutic advantages are manifold, predominantly attributed to its antioxidant and anti-inflammatory properties, its efficacy is hindered by poor bioavailability stemming from inadequate absorption, rapid metabolism, and elimination. To address this challenge, nano-delivery systems have emerged as a promising approach, offering enhanced solubility, biocompatibility, and therapeutic effects for curcumin. We have analyzed the knowledge on curcumin nano-encapsulation and its synergistic effects with other compounds, extracted from electronic databases. We discuss the pharmacokinetic profile of curcumin, current advancements in nano-encapsulation techniques, and the combined effects of curcumin with other agents across various disorders. By unifying existing knowledge, this analysis intends to provide insights into the potential of nano-encapsulation technologies to overcome constraints associated with curcumin treatments, emphasizing the importance of combinatorial approaches in improving therapeutic efficacy. Finally, this compilation of study data aims to inform and inspire future research into encapsulating drugs with poor pharmacokinetic characteristics and investigating innovative drug combinations to improve bioavailability and therapeutic outcomes.

The need to alleviate the difficulties of abstraction and improve students’ achievement in Physical Geography informed this research. This study investigated the Effects of Mastery Learning Strategy and Learning Retention on Senior Secondary School Students’ Achievement in Physical Geography. The study adopted the quasi experimental non-equivalent pre-test, post-test control group design. The Multi-stage sampling technique at four levels was used to select four co-educational secondary schools in Ganye Educational Zone in Nigeria. The sample for the study was 218 Senior Secondary School two (SS II) students offering Geography from four intact classes in the four selected secondary schools. The instrument used for data collection was “Physical Geography Achievement and Retention Test” (PGART). The reliability of the instrument was established using Kendall tau b statistic. This gave a reliability index of 0.74. Data collected were analyzed using Mann-Whitney U and t-Test. The results showed that Mastery Learning Strategy has the potentials to improve students’ learning outcomes, retention and achievement in all spheres of cognitive domain in Physical Geography better than the Conventional Method. Hence the need to incorporate this teaching strategy during instruction so that learners would be guided to learn meaningfully and be assisted to retain content learnt in Geography.

Abstract: Transcription factors are crucial pre-transcriptional regulatory mechanisms that can modulate the expression of downstream genes by binding to their promoter regions. DOF (DNA binding with One Finger) proteins are a unique class of transcription factors with extensive roles in plant growth and development. Our previous research indicated a decrease in iron content in chlorotic bamboo leaves. However, to our knowledge, genes related to iron metabolism pathways in bamboo species have not yet been studied. Therefore, in the current study, we identified iron metabolism-related (IMR) genes in bamboo and determined the transcription factors that significantly influence them. Among these, DOFs were found to have widespread effects and potentially significant impacts on their expression. We identified specific DOF members in Dendrocalamus latiflorus with binding abilities through homology with Arabidopsis DOF proteins, and established connections between some of these members and IMR genes using RNA-seq data. Additionally, molecular docking confirmed the binding interactions between these DlDOFs and the DOF binding sites in the promoter regions of IMR genes. The co-expression relationship between the two gene sets was further validated using q-PCR experiments. This study paves the way for research into iron metabolism pathways in bamboo and lays the foundation for understanding the role of DOF transcription factors in D. latiflorus.

Background: The control of energy metabolism is fundamental for cell growth and function, and anomalies are implicated in complex diseases and ageing. It is important for cells to carefully tune metabolic pathways to optimize their function in response to different nutrient or physiological conditions. Metabolism in yeast cells can be easily manipulated by supplying different carbon sources: on glucose yeast rapidly proliferates by fermentation, analogous to tumour cells growing by aerobic glycolysis, whereas on non-fermentable carbon sources metabolism shifts towards respiration. Results: We screened deletion libraries of fission yeast to identify over 200 genes required for respiratory growth. The growth medium and auxotrophic mutants strongly influenced respiratory metabolism. Most genes uncovered in the mutant screens have not been implicated in respiration in budding yeast. We applied gene expression profiling approaches to compare steady-state fermentative and respiratory growth and to analyse the dynamic adaptation to respiratory growth. The transcript levels of most genes functioning in key energy metabolism pathways were coherently tuned, reflecting anticipated differences in metabolic flows between fermenting and respiring cells. We show that the acetyl-CoA synthase, rather than the citrate lyase, is essential for acetyl-CoA synthesis in fission yeast. We also investigated the transcriptional response to mitochondrial damage by genetic or chemical perturbations, defining a retrograde response that involves the concerted regulation of distinct groups of nuclear genes that may avert harm from mitochondrial malfunction. Conclusions: These systematic and targeted analyses provide a rich framework of the genetic and regulatory basis of fundamental metabolic states to guide future studies on energy metabolism in fission yeast and beyond. Our study pinpoints weaknesses of commonly used auxotroph mutants for investigating energy metabolism. As a model for cellular energy regulation, fission yeast provides an attractive and complementary system to budding yeast.

Iron is an essential nutrient for humans and microbes, such as bacteria. Iron deficiency occurs commonly in critically ill patients, but iron replacement therapy is not considered during the acute phase of critical illness, since it increases iron availability for invading microbes and oxidative stress. However, persistent iron deficiency in the recovery phase is harmful with potential adverse outcomes such as cognitive dysfunction, fatigue and cardiopulmonary dysfunction. Therefore, it is important to treat iron deficiency timely and efficiently. This article reviews current knowledge about iron-related biomarkers in critically ill patients and provides possible criteria to guide decision-making for iron supplementation in the recovery phase of critical illness.

The amino acid proline accumulates in plants during abiotic stresses such as drought and salinity and is considered a reliable marker of environmental stress. While its accumulation is well established, its precise role in stress tolerance and its underlying molecular mechanism remain less clear. To address these issues, we performed a meta-analysis - a robust statistical technique that synthesizes results from multiple independent studies while accounting for experimental differences. We focused on 16 physiological and morphological parameters affected by drought and salt stress in transgenic plants expressing proline metabolic genes. For each parameter, we calculated the effect size as the response ratio (RR), which represents the logarithm of the mean value in the transgenic group over the mean value of the control group (lnRR). Under stress, most parameters exhibited significantly higher response ratios in the transgenic group, confirming the beneficial effects of proline during drought and salt stress. Surprisingly, under non-stressed conditions, most stress markers showed no significant differences between transgenic and non-transgenic plants, despite elevated proline levels in the former. These results suggest that the benefits of proline may be related to proline catabolism or may only become apparent during stress, possibly due to interactions with reactive oxygen species (ROS), which accumulate predominantly under stress conditions.

Fungi are rich sources of secondary metabolites of agrochemical, pharmaceutical and food importances, such as mycotoxins, antibiotics and antitumor agents. Secondary metabolites play vital roles in fungal pathogenesis, growth and development, oxidative status modulation, and adaptation/resistance to various environmental stresses. LaeA contains an S-adenosylmethionine binding site and displays methyltransferase activity. The members of velvet proteins include VeA, VelB, VelC, VelD and VosA, for each member with a velvet domain. LaeA and velvet proteins can form multimeric complexes such as VosA-VelB and VelB-VeA-LaeA. They belong to global regulators and are mainly impacted by light. One of their most important functions is to regulate gene expression that are responsible for secondary metabolite biosynthesis. The aim of this mini-review is to represent the newest cognition on the biosynthetic regulation of mycotoxins and other fungal secondary metabolites by LaeA and velvet proteins. In most cases, LaeA and velvet proteins positively regulated production of fungal secondary metabolites. The regulated fungal species mainly belong to the toxigenic fungi from the genera of Alternaria, Aspergillus, Botrytis, Fusarium, Magnaporthe, Monascus, and Penicillium for the production of mycotoxins. We can control secondary metabolite production to inhibit the production of harmful mycotoxins while promoting the production of useful metabolites by global regulation of LaeA and velvet proteins in fungi. Furthermore, the regulation by LaeA and velvet proteins should be a practical strategy in activating silent biosynthetic gene clusters (BGCs) in fungi to obtain previously undiscovered metabolites.

Salmonella infections can lead to intestinal inflammation and metabolic disorders in birds. However, whether ARA metabolism is involved in Salmonella-induced intestinal inflammation remains unclear. This experiment investigated the changes in cecal flora and arachidonic acid (ARA) metabolism in Hainan Wenchang chickens infected with S. Typhimurium using 16s rDNA sequencing and targeted metabolomics. The results showed that the levels of ARA metabolites were increased in the cecum tissue of Wenchang chickens after infection with S. Typhimurium, including prostaglandin E2, prostaglandin F2α, lipoxin A4, ±8(9)-EET, ±11(12)-EET, and ±8,9-DiHETrE. The content of key enzymes for ARA production and metabolism (PLA2 and COX-2) in chicken cecum tissues was increased after S. Typhimurium infection. The relative mRNA levels of inflammatory factors were also increased after infection, including IFN-γ, TGF-β1, IL-4, and IL-6. In HD11 cells, the use of a cyclooxygenase (COX) inhibitor reduced the increased levels of COX-2 and PGF2α induced by S. Typhimurium infection and effectively reduced the inflammatory response. In addition, the number of beneficial genera (e.g., Bifidobacterium, Lactobacillus, and Odorobacterium) in the cecum of Wenchang chickens was significantly reduced after infection with S. Typhimurium. In this study, we revealed the structure of the cecal flora of Wenchang chickens infected with S. Typhimurium and demonstrated that S. Typhimurium can mediate the onset and development of intestinal inflammation through the activation of the metabolic pathway of ARA cyclooxygenase in Wenchang chickens. The results can provide data support and theoretical support for the prevention and control of avian salmonellosis.

Lipid-lowering therapy (LLT) is a cornerstone of atherosclerotic cardiovascular disease prevention. Although LLT might lead to different reductions in low-density lipoprotein cholesterol (LDL-C) levels in women and men, LLT diminishes cardiovascular risk equally effectively in both sexes. Despite similar LLT efficacy, the use of high-intensity statin, ezetimibe, and proprotein convertase subtilisin/kexin type 9 inhibitors is lower in women compared to men. Women achieve the guideline-recommended LDL-C levels less often than men. Greater cholesterol burden is particularly prominent in women with familial hypercholesterolemia. In clinical practice, women and men with dyslipidemia present with different cardiovascular risk profiles and disease manifestations. The concentrations of LDL-C, lipoprotein(a) and other blood lipids differ between women and men over a lifetime. Dissimilar levels of LLT’s target molecules partially result from sex-specific hormonal and genetic determinants of lipoprotein metabolism. Hence, to evaluate a potential need for sex-specific LLT, this comprehensive review (i) describes the impact of sex on lipoprotein metabolism and lipid profile, (ii) highlights sex differences in cardiovascular risk among patients with dyslipidemia, (iii) presents recent, up-to-date clinical trial and real-world data on LLT efficacy and safety in women, and (iv) discusses diverse medical needs of women and men with dyslipidemia and increased cardiovascular risk.

Background. Cervical esophageal reconstruction is vital for improving the quality of life in cancer surgery patients. Microsurgery is crucial, providing vascularized tissue for defect repair, particularly in secondary cases with a higher risk of failure due to larger defects and damage from previous surgery and radiotherapy. The purpose of this study was to describe the clinical characteristics of a series of patients who underwent secondary repair of esophageal defects and provide practical information for the management and treatment of such cases based on the authors' experience and the literature review. Methods. We retrospectively reviewed the electronic medical records of the Plastic Surgery Clinic at the University of Trieste to identify cases of patients who underwent secondary esophageal microsurgical reconstructions following oncological surgery. Patient demographics, etiology of esophageal defects, previous surgical history, and preoperative assessments were collected from medical records. Surgical techniques employed for reconstruction, such as pedicled flaps or free tissue transfers, were documented along with intraoperative details. Postoperative outcomes, including complications, graft viability, and functional outcomes, were evaluated during follow-up. Results. We treated 13 cases of secondary esophageal reconstructions from 2011 to 2022. Most commonly, Antero-Lateral Thigh (ALT) flaps were used in 10 cases, while 2 cases employed Radial Forearm Flap (RFF), and 1 a chimeric parascapular flap. No flap failures occurred during a median 50-month follow-up. One ALT flap patient experienced post-op stricture but maintained swallowing ability. A single tracheoesophageal fistula occurred in a RFF patient with a history of radiotherapy and completion lymph node dissection. Conclusions. Cervical esophageal reconstruction significantly impacts patients' quality of life by restoring oral feeding and phonation. When local flaps fall short, microsurgical reconstruction with intestinal flaps is valuable, but burdened by limitations. For challenging secondary cases, ALT or RFF flaps emerge as safer options due to their robust pedicles, yielding low complication rates and positive functional outcomes.

Recent studies have demonstrated a relationship between poor vitamin D status and respiratory infections and diarrhea among young children. Acute lower respiratory infections (ALRI) and diarrhea are among the two most important causes of death in under-5 children. In this analysis, we examine the extent to which vitamin-D deficiency (<10 ng/ml) predicts these outcomes using data from a randomized controlled trial (RCT) of daily folic acid and/ or vitamin B12 supplementation for six months in 6 to 30 months old children conducted in Delhi, India. Of the 960 subjects who had vitamin-D concentrations measured, 331(34.5%) were vitamin-D deficient. We found, after controlling for relevant potential confounders (age, sex, breastfeeding status, wasting, stunting, underweight, anemia status at base line and season), the risk of ALRI was significantly higher among vitamin-D deficient (OR 1.26; 95% CI: 1.03 to 1.55) compared to vitamin-D-replete children in the six months follow-up period. Vitamin-D status was not significantly associated with episodes of diarrhea and clinical pneumonia. The extent of causal relationship of vitamin-D status and ALRI needs to be explored in further studies.

Carbohydrates and lipids integrate into a complex metabolic network that is essential to maintain homeostasis. In insects, as in most metazoans, dietary carbohydrates are taken up as monosaccharides whose excess is toxic, even at relatively low concentrations. To cope with this toxicity, monosaccharides are stored either as glycogen or neutral lipids, the latter constituting a quasi-unlimited energy store. Breakdown of these stores in response to energy demand depends on insect species and on several physiological parameters. In this chapter, we review the multiple metabolic pathways and strategies linking carbohydrates and lipids that insects utilize to respond to nutrient availability, food scarcity or physiological activities.

Tryptophan, an essential amino acid in mammals obtained from the diet, is influenced by maternal diet, which impacts early life and development of offspring. This is studied under the Developmental Origins of Diseases and Health (DOHaD) concept, so factors from conception to early childhood affect health and disease susceptibility. Tryptophan is metabolized mainly through two pathways: serotonin (5-HT) and kynurenine. The kynurenine pathway, active in the brain, gut, liver, and placenta, breaks down over 95% of tryptophan and plays roles in inflammation, neurotransmission, immune responses, and immune modulation during pregnancy. The serotonin pathway uses up to 5% of Tryptophan, mainly in the gut, adipose tissues, pancreatic cells, and central nervous system, and regulates responses to environmental changes, including sleep, cognition, and feeding behavior. Key enzymes in these pathways include Trp-2,3-dioxygenase (TDO), indoleamine-2,3-dioxygenase (IDO) type1 (IDO1), and type 2 (IDO2) (kynurenine pathway), and tryptophan hydroxylase type 1 (TPH1) and type 2 (TPH2), serotonin pathway. The fetus-placental unit manages tryptophan metabolism. Serotonin and kynurenine are crucial for placental health and fetal development. Serotonin adjusts placental blood volume and aids neurodevelopment. Kynurenine metabolites protect the fetus from maternal immunity and offer initial neuroprotection. At birth, infants switch from placental nutrients to breast milk, rich in tryptophan and protective bioactive molecules. Tryptophan, solely from breast milk, is crucial for infants. Its levels are high in newborns (first three weeks, 2-4 times higher than in adults), gradually declining to adult levels by the fourth week. The highlights the importance of tryptophan for the serotonin and kynurenine pathways in fetuses, newborns and babies applied to the DOHaD concept.

Introduction: A plethora of biological molecules regulate chondrogenesis in the epiphyseal growth plate. Disruptions of quantity and function of these molecules can manifest clinically as stature abnormalities of various etiologies. Traditionally, the growth hormone/insulin-like growth factor 1 (IGF1) axis represents the etiological center of final stature attainment. Of note, little is known about the molecular events that dominate the growth of the craniofacial complex and its correlation with somatic stature. Aim: Given the paucity of the relevant data, this review discusses available information regarding potential applications of lateral cephalometric radiography as a potential clinical indicator of genetic short stature in children. Materials and Methods: A literature search was conducted in the PubMed electronic database using the key words: cephalometric analysis and short stature; cephalometric analysis and achondroplasia; cephalometric analysis and hypochondroplasia; cephalometric analysis and skeletal abnormalities; cephalometr* and SHOX; cephalometr* and CNP; cephalometr* and ACAN; cephalometr* and CNVs; cephalometr* and IHH; cephalometr* and FGFR3; cephalometr* and Noonan syndrome; cephalometr* and “Turner syndrome”; cephalometr* and achondroplasia. Results: In individuals with genetic syndromes causing short stature, linear growth of the craniofacial complex is confined, following the pattern of somatic short stature regardless of its etiology. The angular cephalometric measurements differ from the average height normal individuals and are suggestive of a posterior placement of the jaws and a vertical growth pattern of the face. Conclusion: The greater part of the existing literature regarding cephalometric measurements in short statured children with genetic syndromes provides qualitative data. Furthermore, cephalometric data for individuals affected with specific rare genetic conditions causing short stature, should be the focus of future studies. These quantitative data are required to potentially establish cut-off values to refer for genetic testing based on craniofacial phenotypes.

(1) Background: a study was undertaken to determine the prevalence of chronic diseases and health conditions that affect oral health and oral health self-care among independent living older adults in rural areas of Victoria, Australia; (2) Methods: The study analysed data from the Crossroads-II project, with a total of 1407 participants aged 55 years and older. Participants self-completed questionnaires about health conditions, service use, and demographics. 572 attended a 2-hour health screening that included an assessment of prescribed medications; (3) Results: Most participants were female (55.3%), with a mean age of 69.1 (SD=9.2) years. Participants had a high prevalence of medical conditions, the most common were high blood pressure, arthritis, high lipids, hearing loss, and chronic pain. Almost all participants reported taking medications, with an average of 4.3 medications per person. Among those who attended the health screening, 78.1% were taking medications that could cause xerostomia (dry mouth); (4) Conclusions: This study provides initial information on the prevalence of medical conditions, medication usage, with potential impact on oral health of older adults living in rural Victoria. This information would be valuable for healthcare and dental workforce planning, policy development, and improving the overall well-being of this population.

Iron metabolism plays a crucial role in the management of hemoglobinopathies, particularly in conditions such as β-thalassemia and sickle cell anemia (SCA). This paper describes the mechanisms of iron overload in patients with transfusion-dependent thalassemia (TDT), non-transfusion-dependent thalassemia (NTDT), and SCA, highlighting the distinct paths leading to iron accumulation in each condition. The primary focus of this review article is on the role of genetic modifiers influencing iron metabolism and the variability in iron overload presentation among patients. Genetic mutations in genes such as HFE, HAMP, TFR2, SLC40A1, and others significantly impact iron regulation. These modifiers can exacerbate or ameliorate iron overload, and understanding these genetic factors is important for explaining the diverse disease severity and differences in the mechanism and clinical presentation of iron overload in these patients. The ongoing INHERENT study aims to further elucidate the influence of these genetic modifiers through a comprehensive genome-wide association study, potentially leading to novel therapeutic interventions for managing iron homeostasis in hemoglobinopathy patients.

Non-coding RNAs have been described as crucial regulators of gene expression and guards for cellular homeostasis. Some recent papers are focused on vault RNAs, one of the classes of non-coding RNA, and their role in cell proliferation, tumorigenesis, apoptosis, cancer response to therapy, and autophagy, which made them potential therapy targets in oncology. In the human genome, four vault RNA paralogues can be distinguished. They are associated with vault complexes, considered the largest ribonucleoprotein complex. The protein part of these complexes consists of a major vault protein (MVP) and two minor vault proteins (vPARP and TEP1). The name of the complex, as well as vault RNA, comes from the hollow barrel-shaped structure that reminds a vault. Their sequence and structure are highly evolutionary conserved and show many similarities in comparison with different species, but vault RNAs show various roles. Vaults were discovered in 1986, and their functions remained unclear for many years. Although not much is known about their contribution to cell metabolism, it has become clear that vault RNAs are involved in various processes and pathways associated with cancer progression and modulating cell functioning in normal and pathological stages. In this review, we discuss known functions of the human vault RNAs in the context of cellular metabolism, emphasizing processes related to cancer and cancer therapy efficacy.

Pulmonary complications are frequently observed in patients with ulcerative colitis (UC), with large airway disease being the most prevalent manifestation. In this case study, we explore the potential for Immunosuppressant, a monoclonal antibody, to induce pulmonary hemorrhage—a side effect not previously documented with its use. The subject, a young male in his twenties with a six-year history of UC, tragically died suddenly. Found in a pool of blood without external injuries, extensive post-mortem examinations were required to determine the cause of death. The patient had been on biologic therapy, receiving Immunosuppressant intermittently over the past two years, including an infusion five days prior to death. External examination revealed bloody, pinkish foamy material expelling from his nose and mouth. An autopsy supported an atypical presentation of UC, while histopathology confirmed diffuse pulmonary hemorrhage, marked by edema and emphysematous changes. Additionally, there was a notable lymphomonocytic infiltration around the arterial walls, and signs of bronchiolitis and focal pleural fibrosis were evident. We concluded that the cause of death was Diffuse Alveolar Hemorrhage (DAH), directly associated with the recent administration of Immunosuppressant. This finding underscores the need for vigilant pulmonary monitoring in patients treated with monoclonal antibodies to promptly identify and manage potential fatal adverse reactions.

The aim of our study was a comprehensive comparative assessment of the effect of consumption of 1 and 2% cholesterol as part of a standard diet with and without regular moderate physical activity on the main biomarkers of lipid and cholesterol metabolism, as well as the intestinal microbiota of male Wistar rats. The animals were randomly divided into 5 groups according to body weight and Open Field test results: Control (n=10), 1% Chol (n=10), 2% Chol (n=10), 1% Chol + RUN (n=10) and 2% Chol + RUN. The cholesterol was additionally added in the amount of 1g or 2g/100g, respectively, to the diet of animals. The rats of experimental groups 1% Chol + RUN and 2% Chol + RUN were subjected to regular (2 days a week) physical activity on a Treadmill. In rats of four experimental groups, when compared to the Control, a response of 39 indicators was revealed. The largest number of changes in biomarkers - 29 (statistically significant, p

The uncertainty in the secondary path of an Active Noise Control (ANC) headphone affects the waterbed effect and stability of the feedback system. This study focuses on the uncertainty of the secondary path when real users wear headphones, and proposes a new uncertainty constraint based on the measured results of the secondary path transfer function under different wearing conditions of dummy head and limited subjects. This constraint and a cascaded second-order infinite impulse response filter with fixed coefficients are used to formulate a control strategic function, which is optimized by the Improved Grey Wolf Optimizer (IGWO) algorithm to obtain the optimal controller with better noise reduction performance. The proposed method and simulation model are validated based on the experimental test results. The results demonstrate that the safety factor and waterbed suppressing factor contained in the proposed uncertainty constraint ensures more stable noise reduction and effective suppression of the waterbed effect for new subjects without a priori data.

The aim was to identify if surface electromyography (sEMG) parameters are indicative of post-activation potentiation (PAP)/post-activation performance enhancement (PAPE), in terms of twitch potentiation and voluntary performance. Three databases were used in March 2024, with the following inclusion criteria: (a) original research, assessed in healthy human adults, (b) sEMG parameters were measured. The exclusion criteria were: (a) studies with no PAP/PAPE-protocol, (b) non-randomized control trials. The following data were extracted: study characteristics/demographics, PAP/PAPE-protocols, sEMG parameters, twitch/performance outcomes, and study findings. A modified physiotherapy evidence database (PEDro) scale was used for quality assessment. Fifteen randomized controlled trials (RCTs), with a total of 199 subjects were included. The M-wave amplitude (combined with a twitch torque outcome) was shown to generally be indicative of PAP. The sEMG amplitude (in some muscles) were found to be indicative of PAPE during ballistic movements, while a small decrease in the MdF (in certain muscles) were shown to reflect PAPE. Changes in the Hmax/Mmax ratio were found to contribute (temporally) to PAP, while the H-reflex amplitude was shown to be neither indicative of PAP nor PAPE. This review provides preliminarily findings suggesting that certain sEMG parameters could be indicative of PAP/PAPE. However, future research is warranted.

Our aim was to determine the secondary antibody deficiency profiles of patients in a mesoregion of São Paulo state, Brazil, focusing on infectious diseases. Demographic characteristics, clinical and laboratory data were obtained from electronic files; infections were classified as organ-specific and graded as mild, moderate, life-threatening, and fatal. Non-Hodgkin lymphoma (NHL) accounted for 30% of patients, nephrotic syndrome (NS) 25%; chronic lymphocyte leukemia 20%, and multiple myeloma 15%. Patients with NS were younger than those in other groups, and hypo-γ-globulinemia was detected in 94.1%, IgG <400 mg/dL in 60.0%, IgA <40 mg/dL in 55.0%, and CD19 <20 cells/mm³ in 30.0%. One hundred and one infections were found; 82.1% were classified as mild or moderate, 7.9% as life-threatening, and 1.9% as fatal. Respiratory tract infections were more prevalent (41.5%), and pneumonia accounted for 19.8%. Lower levels of infections were found in patients with NS compared with NHL (P=0.0001). Most patients progressed to hypo-γ-globulinemia and secondary antibody deficiency after treatment with immunosuppressants, and mild and moderate infections were predominant. These therapies are increasing in patients with different diseases, therefore monitoring hypo-γ-globulinemia and infections may help to identify patients at high risk for severe complications, antibiotic prophylaxis or treatment, and immunoglobulin replacement

The combined use of lasmiditan and triptan is unexplored in medical literature. This study aimed to investigate whether the intake of lasmiditan following triptan improves migraine pain. Following triptan intake, if headache relief was less than 50% at 1 hour, patients took 50 mg lasmiditan within 2 hours of migraine onset. Patients recorded headache intensity and adverse events(AEs) caused by lasmiditan at 1, 2, and 4 hours after intake of additional 50 mg of lasmiditan. A significant reduction in pain scale was observed post 50 mg lasmiditan intake (p &lt; 0.001, t-test). Pain relief was reported for 32 migraine attacks (80%) at 1 hour after additional lasmiditan intake. Although AEs were observed in 63% of the patients who took an additional lasmiditan, most were mild and resolved 1 hour after lasmiditan intake. Our study revealed the significant headache reliefs provided by an additional lasmiditan for patients who did not achieve satisfactory results following initial triptan intake for treating migraine. The AEs associated with this treatment strategy were mild and lasted for a short term. This study suggested that the combination of triptan and lasmiditan is promising for the treatment of migraine and should be studied in a randomized placebo-controlled trial.

Deuterium is a heavy nonradioactive isotope of hydrogen, having a neutron as well as a proton, making it twice as heavy. It is a natural element, present at 156 parts per million in seawater. The ATPase pumps in the mitochondria utilize proton motive force to drive ATP synthesis, and deuterons damage the pumps, producing a stutter that can cause reactive oxygen release and inefficiencies in ATP synthesis. Cellular metabolism incorporates several novel mechanisms to assure low deuterium content in the mitochondria and other organelles. Nicotinamide adenine dinucleotide (NAD) is a major carrier of deuterium depleted (deupleted) protons to supply the mitochondria. Many enzymes, especially flavoproteins, are able to use proton tunneling to fractionate out deuterium. In this paper, we argue that the amino acid proline is able to trap and sequester deuterium, and that peptidyl prolyl isomerases (PPIases) play a central role in facilitating deuterium trapping in proline-rich proteins, most notably collagen. The endothelial glycocalyx also sequesters deuterium in gelled water lining the blood vessels, creating a battery and promoting low deuterium in the circulation. Excess deuterium promotes cancer growth, and cancer cells release large quantities of lactate via aerobic glycolysis to help reverse deuterium overload, systemically.

Estrogen receptor-positive (ER+) breast cancer is common among postmenopausal women and is frequently treated with Letrozole. Letrozole inhibits aromatase from synthesizing estrogen from androgens. Decreased estrogen slows the growth of tumors and can be an effective treatment. Letrozole resistance is increasingly being observed, which poses a unique problem for patients. We reanalyzed transcriptomic data comparing individuals who responded to Letrozole therapy (responders) to those who were resistant to treatment (non-responders). We identified SOX11 and S100A9 as two genes that significantly differed between these patients; with “PLK1 signaling events” being the most significant signaling pathway. We also identified PRDX4 and E2F8 as the top transcriptional biomarkers for ER+ treatment resistance. Many of the other significant gene products play a known role in ER+ breast cancer or other types of cancer, which partially validate our results. Several of the gene products we identified do not have a characterized role in ER+ breast cancer. Our analysis identified a set of genes that warrant further research to elucidate the molecular mechanism of Letrozole resistance in this patient population, as well as novel high-performing biomarkers. We anticipate that these findings could contribute to improved therapeutic outcomes in human patients.

Intermittent religious fasting increases a risk of hypo- and hyperglycemia in individuals with diabetes, but its impact in those without diabetes is poorly investigated. The study aim was to examine the effects of religious Bahá'í fasting (BF) on glycemic control and variability and compare these effects with time-restricted eating (TRE). In a three-arm randomized controlled trial, 16 subjects without diabetes were assigned to a BF, 16:8 TRE or control group. Continuous glucose monitoring and food intake documentation was conducted before and during the 19 days of intervention, and 24-hour mean glucose, glycemic variability indices, and glucotypes were assessed. BF and TRE groups, but not the control group, markedly reduced the daily eating window while maintaining macronutrient composition. Only the BF group decreased caloric intake (-677.8 ± 357.6 kcal, p=0.013), body weight (-1.92 ± 0.95 kg, p=0.011) and BMI (-0.65 ± 0.28 kg, p=0.006). Higher maximum glucose values were observed during BF in the within-group (+1.41 ± 1.04, p=0.039) and between-group comparison (BF vs. Control: p= 0.010 and TRE vs. BF: p= 0.022). However, there were no alterations of 24-hour mean glucose, intra- and inter-day glycemic variability indices, or glucotypes in any group. Proportions of time above and below range (70-180mg/dl) and HbA1c values remained unchanged. BF and TRE do not exhibit negative effects on glycemic control and variability in subjects without diabetes.

Central nervous system (CNS) myelin has a crucial role in accelerating the propagation of action potentials and providing trophic support to the axons. Defective myelination and lack of myelin regeneration following demyelination can both lead to axonal pathology and neurodegeneration. Energy deficit has been evoked as an important contributor to various CNS disorders, including multiple sclerosis (MS). This suggests that dysregulation of energy homeostasis in oligodendroglia may be an important contributor to myelin dysfunction and lack of repair observed in the disease. This article will focus on energy metabolism pathways in oligodendroglial cells and highlight differences dependent on the maturation stage of the cell. In addition, it will emphasize that the use of alternative energy sources by oligodendroglia may be required to save glucose for functions that cannot be fulfilled by other metabolites, thus ensuring sufficient energy input for both myelin synthesis and trophic support to the axons. Finally, it will point out that neuropathological findings in a subtype of MS lesions likely reflect defective oligodendroglial energy homeostasis in the disease.

Gestational diabetes mellitus (GDM) triggers alterations in the maternal gut microbiome. Alongside metabolic shifts, microbial products may impact clinical factors and influence pregnancy outcomes. Here, we performed two separate analyses to integrate the maternal microbiome-metabolomic differences from a subset of the “Choosing Healthy Options in Carbohydrate Energy” (CHOICE) study. Women diagnosed with GDM were randomized to a diet higher in complex carbohydrates (CHOICE, n=18, 60% complex carbohydrate/25% fat/15% protein) or a conventional GDM diet (CONV, n=16, 40% carbohydrate/45% fat/15% protein). All meals were provided, diets were eucaloric, and fiber content was similar. CHOICE diet was associated with increases in TMAO, lysophosphotidylcholines, indoxyl sulfate, and several triglyceride (TG) species, while CONV diet was associated with higher plasma hippuric acid, aspartic acid, betaine, glutamic acid, indole propionic acid, and indoleacetic acid, suggesting that differences in lipid metabolism and tryptophan utilization pathways are linked to specific maternal diets. We also identified two latent metabolic groups not associated with either diet treatment: one metabolome associated with higher fasting glucose, and the other associated with higher fasting TGs after 7 weeks on either diet. Our study underscores the importance of utilizing dietary approaches to optimize maternal-fetal health outcomes in GDM treatment.

A Cu₂ZnSnS₄ (CZTS) film with a thickness of approximately 1.5 μm was fabricated on a Mo-coated glass substrate by annealing a CZTS precursor fabricated from nanoparticle ink. The chemical states of the elements in the CZTS thin film in the depth direction were studied to identify the presence of secondary phases, which are detrimental to the performance of solar cells containing CZTS. X-ray diffraction was unable to detect any secondary phases in CZTS because of their small relative amount. Instead, X-ray photoelectron spectroscopy (XPS), which is highly sensitive to chemical state, was conducted at different depths in the CZTS film to further check the presence of secondary phases. XPS analysis revealed peaks shift consistent with the presence of secondary phases. For the CZTS film annealed in a S atmosphere at 575 °C for 3 h, the film surface consisted of a secondary-phase layer composed of CuS, ZnS, and SnSx (x=1 or 2) originating from the decomposition of CZTS. At depths below 80 nm, the film was pure CZTS. Formation of MoS2 at the CZTS–Mo interface was confirmed by XPS analysis of Mo and S.

Probiotic feed additives have attracted considerable research interest in recent years because the effectiveness of probiotics can differ across microbial strains and the supplemented macroorganisms. The present study was conducted on 16 lambs divided into two groups (C - control and E - experimental). The examined lambs were aged 11 days at the beginning of the experiment and 40 days at the end of the experiment. The diet of group E lambs was supplemented with a multi-strain probiotic formulation (Lactobacillus plantarum AMT14, Lactobacillus plantarum AMT4, Lactobacillus rhamnosus AMT15, and Bifidobacterium animalis AMT30), whereas group C lambs did not receive the probiotic additive. At the beginning of the experiment (day 0) and on experimental days 15 and 30, blood was sampled from the jugular vein to determine and compare: phagocytic activity (PHAGOTEST) and oxidative metabolism (PHAGOBURST) of peripheral blood granulocytes and monocytes by flow cytometry. An analysis of the phagocytic activity of granulocytes and monocytes revealed significantly higher levels of phagocytic activity (expressed as the percentage of phagocytic cells and mean fluorescence intensity) in lambs administered the multi-strain probiotic formulation than in the control group. The probiotic feed additive also exerted a positive effect on the oxidative metabolism of both granulocytes and monocytes (expressed as the percentage of oxidative metabolism and mean fluorescence intensity) after stimulation with Escherichia coli bacteria and with PMA (4-phorbol-12-β-myristate-13-acetate).

Rhodiola rosea, a perennial herb from the Crassulaceae family, contains the bioactive compound salidroside, recognized as an adaptogen with significant therapeutic potential for bone metabolism. Salidroside promotes osteoblast proliferation and differentiation by activating critical signaling pathways, including bone morphogenetic protein-2 and adenosine monophosphate-activated protein kinase, essential for bone formation and growth. It enhances osteogenic activity by increasing alkaline phosphatase activity and mineralization markers, while upregulating key transcription factors such as runt-related transcription factor 2 and osterix. Additionally, salidroside facilitates angiogenesis via the hypoxia-inducible factor 1-alpha and vascular endothelial growth factor pathway, crucial for coupling bone formation with vascular support. Its antioxidant properties offer protection against bone loss by reducing oxidative stress and promoting osteogenic differentiation through the nuclear factor erythroid 2–related factor 2 pathway. Salidroside's ability to counteract the negative effects of glucocorticoids on bone cells and prevent steroid-induced osteonecrosis, along with its anti-inflammatory properties, enhances its potential in treating conditions like osteoarthritis. These attributes underscore its multifaceted role in bone metabolism. This article reviews the literature, including in vitro and in vivo studies primarily on rodent models, demonstrating salidroside's efficacy in mitigating bone loss, preserving bone microarchitecture, and accelerating fracture healing. Future research directions to explore salidroside’s applications in bone-related diseases are also highlighted.

Purpose. This paper aims to present a unique perspective that emphasizes the intricate interplay between energy, dietary proteins, and amino acid composition, underscoring their mutual dependence for health-related considerations. Energy and protein synthesis are fundamental to biological processes, crucial for the sustenance of life and growth of organisms. Methods and Results. We explore the intricate relationship between energy metabolism, protein synthesis, regulatory mechanisms, protein sources, amino acid availability, and autophagy, in order to elucidate how these elements collectively maintain cellular homeostasis. We underscore the vital role this dynamic interplay has in preserving cell life. Conclusion. A deeper understanding of the link between energy and protein synthesis is essential to comprehend fundamental cellular processes. This insight could have wide-ranging impact in several medical fields, such as nutrition, metabolism, and disease management.

Lifestyle interventions can prevent type 2 diabetes (T2DM). However, some in-dividuals do not experience anticipated improvements despite weight loss. Bi-omarkers to identify such individuals at early stages are lacking. IGF-1 and IGFBP-1 were shown to predict T2DM onset in prediabetes. We assessed if these markers also predict the success of lifestyle interventions, thereby possibly guid-ing personalized strategies. We analyzed fasting serum levels of IGF-1, IGFBP-1 and IGFBP-2 in relation to changes in metabolic and anthropometric parameters, including intrahepatic li-pids (IHL) and visceral adipose tissue (VAT) volume measured by MRI, in 345 high-risk prediabetic participants (54% female; aged 36-80 years). Participants were enrolled in three randomized dietary intervention trials and assessed both at baseline and one year post-intervention. Statistical analyses were performed using IBM SPSS Statistics (version 28), significance set at p

Aquatic animals have unique physiological mechanisms to absorb and retain minerals from their diets and water. Research and development in the area of mineral nutrition of farmed fish and crustaceans have been relatively slow and major gaps exist in the knowledge of trace element requirements, physiological functions and bioavailability from feed ingredients. Quantitative dietary requirements have been reported for three macroelements (calcium, phosphorus and magnesium) and six trace minerals (zinc, iron, copper, manganese, iodine and selenium) for selected fish species. Mineral deficiency signs in fish include reduced bone mineralization, anorexia, lens cataracts (zinc), skeletal deformities (phosphorus, magnesium, zinc), fin erosion (copper, zinc), nephrocalcinosis (magnesium deficiency, selenium toxicity), thyroid hyperplasia (iodine), muscular dystrophy (selenium) and hypochromic microcytic anaemia (iron). An excessive intake of minerals from either diet or gill uptake causes toxicity and therefore a fine balance between mineral deficiency and toxicity is vital for aquatic organisms to maintain their homeostasis either through increased absorption or excretion. Release of minerals from uneaten or undigested feed and from urinary excretion can cause eutrophication of natural waters, which requires additional consideration in feed formulation. The current knowledge in mineral nutrition of fish is briefly reviewed.

The increasing prevalence of obesity and sedentary lifestyles has led to an increased incidence of metabolic syndrome (MetS) worldwide. In Taiwan, middle-aged women are at a greater risk of MetS, type 2 diabetes, and cardiovascular disease than men are because they have more subcutaneous fat and larger waist circumferences compared to men with equal visceral fat levels. This study investigated the effects of calorie restriction supplemented with fish oil (CRF) in middle-aged women with MetS. For 12 weeks, 75 eligible participants were randomly assigned either calorie restriction (CR) or CRF. Both dietary intervention groups were further divided into two age groups: ≤45 and >45 years. The changes in MetS severity, inflammatory status, iron status, and red blood cell fatty acid profile were evaluated. Seventy-one participants completed the trial. Both dietary interventions significantly ameliorated MetS and improved the participants’ inflammatory status. CR significantly increased total iron binding capacity, whereas CRF increased hepcidin levels. Furthermore, CRF significantly increased the n-6/n-3 and arachidonic acid/docosahexaenoic acid ratios. In conclusion, CR and CRF improved the anthropometric and MetS characteristics of early-middle aged women, including body weight, blood glucose levels, triglyceride levels, as well as the scores for the homeostasis model assessment of insulin resistance and quantitative insulin sensitivity cheque index. Dietary intervention was more effective in >45-year-old women than ≤45-year-old women.

The aim of this study was to compare the effect of using L-PRF in patients undergoing impacted lower third molar surgery with either primary or secondary closure techniques. Methods: This prospective, randomised, double-blind, split-mouth clinical trial was conducted in patients with bilateral lower impacted third molars of similar position. Primary closure was performed in group 1 and secondary closure in group 2. Group 1 closure technique was applied to one side of the patients and group 2 closure technique was applied to the other side at different times. Nine pa-tients were excluded from the study due to alveolitis and failure to attend regular control visits out of the 45 patients evaluated. Results: Of the 36 patients included in the study, 23 were female and 13 were male and the mean age was 22.42±3.36 years. The secondary closure group had lower VAS scores at hour 6 (p

In intermediary metabolism, enzymes are mainly for the specific provision of one small molecule from another, B from A, for its further use. But there are also decades of work relating to another evolved purpose, which is to prevent untoward effects of odd compounds of various origins, and of ordinary intermediates, whose improper concentrations may be avoided by hydrolases and other activities of metabolic correction.

The water-soluble vitamin - vitamin B12, also known as cobalamin, plays a crucial role in cellular metabolism, particularly in DNA synthesis, methylation, and mitochondrial functionality. Its de-ficiency can lead to hematological and neurological disorders, however the manifestation of these clinical outcomes is relatively late. It leads to difficulties in its early diagnosis, often resulting in the development of hidden subclinical cobalamin deficiency. Prolonged lack of vitamin B12 con-dition may have severe consequences including increased morbidity to neurological and cardio-vascular diseases. Beyond inadequate dietary intake, vitamin B12 deficiency might be caused by insufficient bioavailability, blood transport disruptions, or impaired cellular uptake and metabo-lism. Despite nearly 70 years of knowledge since its isolation and characterization, there are still gaps in understanding its metabolic pathways. Thus, this review aims to gather current knowledge about the crucial proteins necessary to efficiently process vitamin B12 in humans, presenting it as a multi-protein mediated network. Based on these findings, we also highlight new potential methods for supporting the evaluation of the risk of epidemiological consequences of vitamin B12 deficiency or clinical warnings of increased risk of vitamin B12 deficiency based on already testing targeting specific moonlighting proteins engaged in vitamin B12 metabolic path-ways.

Background: The enduring psychological effects of the COVID-19 pandemic continue to affect individuals long after the immediate health concerns have subsided. This research aims to identify specific groups within the Romanian population who are at a higher risk of experiencing mental health challenges that can interfere with everyday life and may lead to more serious mental health disorders. Methods: Conducted as a cross-sectional survey, this study evaluated the prevalence and intensity of psychological distress using the DASS-21 questionnaire. An online survey distributed via Google Forms also gathered socio-demographic data and COVID-19-specific information. Statistical analyses included the Shapiro-Wilk test, Fisher's exact test, and Z-tests with Bonferroni correction. Quantitative independent variables that lacked a normal distribution were compared between groups using either the Mann-Whitney U test or the Kruskal-Wallis H test. Results: Analysis of 521 questionnaires, filled out by a predominantly middle-aged cohort of 320 women and 201 men, revealed that 63.72% of participants worked outside the healthcare field. Those unemployed or retired reported significantly higher anxiety levels than individuals in other sectors. Moreover, living alone, experiencing the loss of close relatives (6.14%) or friends (33.59%), and undergoing hospitalization or reinfection due to COVID-19 were linked to significantly elevated distress scores. Conclusion. By identifying the segments of the population most vulnerable to psychological distress, as evidenced by higher scores among the unemployed, retirees, individuals living alone, and those directly affected by COVID-19 through personal health or loss, targeted initiatives for psychological screening and therapy can be established. Such measures are essential for enhancing the post-pandemic mental well-being of Romanians, addressing the specific needs uncovered in this study.

The formation of hydrogen sulfide (H₂S) in petroleum reservoirs by anaerobic microbial activity is called biogenic souring of reservoirs and is a risk in the oil and gas industry as the compound is extremely toxic, flammable and corrosive. In this paper, we present a workflow and the tools to assess biogenic souring from a pragmatic engineering perspective. The retention of H₂S in the reservoir due to the reactions with iron-bearing rock minerals (e.g. siderite) is shown in a theoretical approach here and supported with literature data. Cases are given for two fields under secondary (waterflooding) and tertiary flooding with microbial enhanced oil recovery (MEOR). The use of the Monte Carlo method as a numerical modelling tool to incorporate uncertainties in the measured physical/chemical/ biochemical data is demonstrated as well. A list of studies conducted with different chemicals alone or in combination with various biocides to mitigate biogenic souring provides an overview of potential inhibitors as well as possible applications. Furthermore, the results of static and dynamic inhibition tests using molybdate are presented in more detail due to its promising mitigation ability. Finally, a three-step workflow for the risk assessment of biogenic souring and its possible mitigation is presented and discussed.

Chikungunya virus (CHIKV) is a mosquito borne RNA virus that poses an emerging threat to humans. As other RNA viruses, CHIKV encodes an error-prone RNA polymerase which, in addition to full-length genomes, gives rise to truncated, non-functional genomes coined defective viral genomes (DVGs). DVGs have been intensively studied in the context of therapy, as they can inhibit viral replication and dissemination in their hosts. In this work, we interrogate the influence of viral RNA secondary structures on the production of CHIKV DVGs. We experimentally map RNA secondary structures of CHIKV genome using selective 2′-hydroxyl acylation analyzed by primer extension and mutational profiling (SHAPE-MaP), which couples chemical labelling with next-generation sequencing. We correlate the inferred secondary structure with preferred deletion sites of CHIKV DVGs. We document an increased probability of DVG generation with truncations at unpaired nucleotides within the secondary structure. We then generated a CHIKV mutant bearing synonymous changes at the nucleotide level to disrupt existing RNA secondary structure (CHIKV-D2S). We show that CHIKV-D2S presents altered DVG generation compared to wild-type virus, correlating with its change in RNA secondary structure obtained by SHAPE-MaP. Our work thus demonstrates that RNA secondary structure impacts CHIKV DVG production during replication.

Animals use dietary lipids to sustain their growth and survival. Insects can synthesize fatty acids (FAs) and are autotroph for a number of lipids, but auxotroph for specific lipids classes (e.g. sterols, polyunsaturated FAs). Once ingested, lipids are hydrolyzed in the intestinal lumen and taken up into intestinal cells within specific regions of the insect digestive tract. These lipids can be either stored in the intestinal cells or exported through the haemolymph circulation to specific organs. In this chapter, we describe the various lipids provided by insect diets, their extracellular hydrolysis in the gut lumen and their intake and metabolic fate in the intestinal cells. This review emphasizes the critical role of the digestive tract and its regionalization in processing dietary lipids prior to their transfer to the requiring tissues.

The members within the genus Thermoanerobacter have been much less investigated for protein and amino acid metabolism as compared with carbohydrates. The present study investigates the biotechnological potential of Thermoanaerobacter mathranii (DSM 11426) concerning its ability to produce high energy alcohols from amino and fatty acids. End-product formation was analyzed from glucose in the presence and absence of butyric acid as well as from selected proteins, and all amino acids. T. mathranii did not degrade any of the proteins tested to a large extent but de-grade several amino acids, namely serine and the branched-chain amino acids (leucine, isoleu-cine, valine) when cultivated in the presence of thiosulfate. The main end products from the branched-chain amino acids were a mixture of their corresponding branched-chain fatty acids and alcohols. 13C2-labeled leucine revealed that the strains degraded the amino acid in the pres-ence of thiosulfate, producing 3-methyl-1-butyrate, which was then used as an electron acceptor which led to the accumulation of 3-methyl-1-butanol. The strain is highly ethanologenic, pro-ducing more than 1.2 mol ethanol per mol of glucose degraded. The strain was able to reduce volatile fatty acids during glucose fermentation to their corresponding alcohol, further suggest-ing this strain may be of greater biotechnological value beyond bioethanol production.

Our recent work has focused on the application of infinite group theory and related algebraic geometric tools in the context of transcription factors and microRNAs. We were able to differentiate between “healthy" nucleotide sequences and disrupted sequences that may be associated with various diseases. In this paper, we extend our efforts to the study of messenger RNA metabolism, showcasing the power of our approach. We investigate (i) mRNA translation in prokaryotes and eukaryotes, (ii) polyadenylation in eukaryotes, which is crucial for nuclear export, translation, stability, and splicing of mRNA, (iii) miRNAs involved in RNA silencing and post-transcriptional regulation of gene expression, and (iv) the identification of disrupted sequences that could lead to potential illnesses. To achieve this, we employ (a) infinite (finitely generated) groups fp, with generators representing the r+1 distinct nucleotides and a relation between them [e.g., the consensus sequence in the mRNA translation (i), the poly(A) tail in item (ii), and the miRNA seed in item (iii)], (b) aperiodicity theory, which connects “healthy groups" fp to free groups Fr of rank r and their profinite completion F^r, and (c) the representation theory of groups fp over the space-time-spin group SL2(C), highlighting the role of surfaces with isolated singularities in the character variety. Our approach could potentially contribute to the understanding of the molecular mechanisms underlying various diseases and help develop new diagnostic or therapeutic strategies.

Glutamine is the most abundant and versatile amino acid in the body. In health and disease, the rate of glutamine consumption by immune cells is similar or greater than glucose. For instance, in vitro and in vivo studies have determined that glutamine is an essential nutrient for lymphocyte proliferation and cytokine production, macrophage phagocytic plus secretory activities and neutrophil bacterial killing. Glutamine release to the circulation and availability is mainly controlled by key metabolic organs, such as the gut, liver and skeletal muscles. During catabolic/hypercatabolic situations glutamine can become essential for metabolic function, but its availability may be compromised due to impairment of homeostasis in the inter-tissue metabolism of amino acids. For this reason, glutamine is currently part of clinical nutrition supplementation protocols and/or recommended for immune suppressed individuals. However, in a wide range of catabolic/hypercatabolic situations (e.g. ill/critically ill, post-trauma, sepsis, exhausted athletes) it is currently difficult to determine whether glutamine parenteral or enteral supplementation should be recommended based on the amino acid plasma concentration (glutaminemia). Although the beneficial immune based effects of glutamine supplementation is already established, many questions and evidence for positive in vivo outcomes still remain to be presented. Therefore, this paper provides an integrated review on how glutamine metabolism in key organs is important to cells of the immune system. We also discuss glutamine metabolism, action and important issues related to the effects of glutamine supplementation in catabolic situations.

Headache is considered to be one of the most common causes of medical treatment and evaluation worldwide in both acute and outpatient settings. It is the most common neurological symptom seen worldwide affecting all genders, ages, ethnicities, and socioeconomic levels. It’s impact is noted in educational decline in school-aged children and decreased productivity through sick leave in adults. Its overall burden is well documented in well-resourced countries but limited data is seen low resourced countries. While many underlying causes bring about secondary headaches, primary headaches and more specifically migraines have been more widely explored. Migraines have a distinct criterion that is inclusive of one day duration (4 hours to 7 days, unilateral distribution, nausea and vomiting and disability as a few examples. However, migraines can vary and proper documentation through a migraine diary can help to guide treatment. Management of migraines can vary. Lifestyle modification is a key factor in the overall prevention and reduction of triggers in migraines. In addition to this, pharmacotherapy can be given in a tier-based approach based on overall severity and frequency of the migraine. Interventions have progressed from botox injection and have seen the advent of new medications such as nasal sprays to novel formulations of pre-existing drug formulations. Nonetheless, there is great room for further studies of headaches and migraines. Research specifically in low-resource countries can prove to beneficial.

Eurotium is the teleomorph genus associated with section Aspergillus. Eurotium comprises approximately 20 species, which are widely distributed in nature and human environments. Eurotium is usually the key microorganism for the ferment ation of traditional food, such as Fuzhuan brick tea, Liupao tea, Meju, and Karebushi, thus Eurotium is an important fungus in food industry. Eurotium has been extensively studied because they contain a series of interesting, structurally diverse, and biologically important secondary metabolites, including anthraquinones, benzaldehyde derivatives, and indol diketopiperazine alkaloids. These secondary metabolites have shown multiple biological activities, including antioxidative, antimicrobial, cytotoxic, antitumor, insecticidal, antimalarial, and anti-inflammatory activities. This study presents an up-to-date review of the phytochemistry and biological activities of all Eurotium species. This review will provide the recent advances on the secondary metabolites and their bioactivities in genus Eurotium for the first time and serve as a database for future research and drug development from the genus Eurotium.

Plant secondary metabolites are organic compounds (alkaloids, flavonoids, phenolics, tannins, anthraquinones, saponins, steroids, lignins, terpenes) produced by plant for self-defense during growth and development in order to protect them from harmful agents. As population is increasing and quality of life is reducing couple with outbreak of some diseases that are posing threat on the economy, a lot of medicinal plants have attracted interest of researchers because of the usefulness of these metabolites in pharmaceuticals, food and cosmetic industries. In this review, the pharmacological activities of some medicinal plants that are rich in secondary metabolites were studied, means of identifying and quantifying using spectrophotometry and chromatography techniques were also discussed. However, this will assist to reduce the uses and dependent on the synthetic drug and the onset of the age related diseases.

Telomeres – special DNA-protein structures at the ends of linear eukaryotic chromosomes define the proliferation potential of cells. Extremely short telomeres promote DNA damage response and cell death to eliminate cells potentially accumulated mutations after multiple divisions. However, telomere elongation is associated with increased proliferative potential of special types of cells, such as stem and germ cells, permanently, and is activated temporally in processes of activation of immune response, regeneration processes. Activation of mechanisms of telomere lengthening coupled with increased proliferation and with requirements of cells in energy and building resourses. To obtain necessary nutrients cells stimulate metabolism by switching of oxidative phosphorylation program to glycolysis. In this review we focused on the interconnection of metabolism program and telomere lengthening mechanisms known for the situation of the programmed activation of proliferation such as germ cells maturation, early embryonic development program and immune response activation. Here, we propose that it is possible to reprogram metabolism in order to regulate the telomere length, proliferative activity of cells that may be important for the development of approaches to regeneration, immune response modulation and cancer therapy and further investigations in this area are necessary to improve the understanding and manipulating of molecular mechanisms used for regulation of proliferation.

The study of the impact of polyQ expansion driven proteotoxicity on cell metabolism has evi-denced NAD molecule as a central player in regulating metabolic response and cell repair in neurodegeneration. The decline in NAD intracellular levels represents a hallmark of ageing aris-ing from a dysregulation between NAD-consuming and biosynthetic enzymatic reactions in which NMNAT plays a key role. By an integrated bioanalytical and proteomic experimental design, the derangement of NAD metabolism deriving from the accumulation of polyQ-Htt protein has been analysed in Saccha-romices cerevisiae harbouring a 103Q-Htt and compared with wild-type Htt, in absence and in presence of a phenolic extract from EVOO, as a source of antioxidant bioactive compounds. Quantification of NAD and its precursors and proteomic analysis of the differential protein ex-pression has been performed by LC-DAD-MS. Chronological lifespan and NAD homeostasis was strongly impaired by proteotoxic polyQ-Htt, eliciting a depletion of NAD levels and accumulation of NaMN. In parallel a downregulation of Sirt2 expression levels has been observed. Phenolic extract administration had no meaningful ef-fects on NAD replenishment to prevent proteotoxicity. NaMN can represent a biomarker of accel-erated aging, and/or a signaling molecule for cell repair.

Traumatic brain injury (TBI) is a devastating event with severe long-term complications. TBI and its sequelae are one of the leading causes of death and disability in those under 50 years old. The full extent of secondary brain injury is still being intensely investigated; however, it is now clear that neurotrauma can incite chronic neurodegenerative processes. Chronic traumatic encephalopathy, Parkinson’s disease, and many other neurodegenerative syndromes have all been associated with a history of traumatic brain injury. The complex nature of these pathologies can make clinical assessment, diagnosis, and treatment challenging. The goal of this review is to provide a concise appraisal of the literature with focus on emerging strategies to improve clinical outcomes. First, we review the pathways involved in the pathogenesis of neurotrauma-related neurodegeneration and discuss the clinical implications of this rapidly evolving field. Next, because clinical evaluation and neuroimaging are essential to the diagnosis and management of neurodegenerative diseases, we analyze the clinical investigations that are transforming these areas of research. Finally, we briefly review some of the preclinical therapies that have shown the most promise in improving outcomes after neurotrauma.

Phytochemicals have a long and successful history in drug discovery. With recent advancements in analytical techniques and methodologies, discovering bioactive leads from natural compounds has become easier. Computational techniques like molecular docking, QSAR modelling and machine learning, and network pharmacology are among the most promising new tools that allow researchers to make predictions concerning natural products' potential targets, thereby guiding experimental validation efforts. Additionally, approaches like LC-MS or LC-NMR speed up compound identification by streamlining analytical processes. Integrating structural and computational biology aids in lead identification, thus providing invaluable information to understand how phytochemicals interact with potential targets in the body. Emerging computational approach is machine learning involving QSAR modelling and deep neural networks that interrelate phytochemical properties with diverse physiological activities such as antimicrobial or anticancer effects.

The focus of our study was the changes in the composition of semi-natural dry grasslands in Hungary. Since these valuable habitats were created with the help of humans, their preservation also requires regular treatment. Our mowing experiment aimed to investigate the suppression of the native Calamagrostis epigejos L. Roth. In Hungary, in the Cserhát Mountains, eight permanent plots were mowed twice a year. The vegetation was sampled annually between 2001 and 2011. The effects of mowing were investigated with repeated measures analysis of variance (ANOVA). After 10 years, the C. epigejos cover of the mowed plots decreased significantly, from the initial average of 62.38 to 7.50%. Surprisingly, we also experienced a similar decrease in the control plots. Regular treatment also had a positive effect on the number of species and diversity. Species richness increased continuously in both treatment types, which indicates the combined effect of vegetation succession and treatment. The biomass growth of other Poaceae and Fabaceae species, which are important from a grassland management perspective, was also facilitated by mowing. Our results suggest that long-term in situ experiments and continuous botanical studies are needed to establish a reliable utilization of grasslands.

(1) Background: Multiple alterations of cellular metabolism have been documented in experimental studies of autosomal dominant polycystic kidney disease (ADPKD) and are thought to contribute to its pathogenesis. (2) Methods: To elucidate the molecular pathways and transcriptional regulators associated with the metabolic changes of renal cysts in ADPKD, we compared global gene expression data from human PKD1 renal cysts, minimally cystic tissues (MCT) from the same patients, and healthy human kidney cortical tissue samples. (3) Results: We found PKD1 renal cysts displayed the Warburg effect with gene pathway changes favoring increased cellular glucose uptake and lactate production, instead of pyruvate oxidation. Additionally, mitochondrial energy metabolism was globally depressed, associated with downregulation of gene pathways related to fatty acid oxidation (FAO), branched-chain amino acid (BCAA) degradation, the Krebs cycle, and oxidative phosphorylation (OXPHOS) in renal cysts. Activation of mTORC1 and its two target proto-oncogenes, HIF-1α and MYC, was predicted to drive the expression of multiple genes involved in the observed metabolic reprogramming (e.g., GLUT3, HK1/HK2, ALDOA, ENO2, PKM, LDHA/LDHB, MCT4, PDHA1, PDK1/3, MPC1/2, CPT2, BCAT1, NAMPT); indeed, their predicted expression patterns were confirmed by our data. Conversely, we found AMPK inhibition was predicted in renal cysts. AMPK inhibition was associated with decreased expression of PGC-1α, a transcriptional coactivator for transcription factors PPARα, ERRα, and ERRγ, all of which play a critical role in regulating oxidative metabolism and mitochondrial biogenesis. (4) Conclusions: These data provide a comprehensive map of metabolic pathway reprogramming in ADPKD and highlight nodes of regulation that may serve as targets for therapeutic intervention.

Vascular calcification (VC), is a common complication in patients with chronic kidney disease and increases mortality. Although oxidative stress is involved in the onset and progression of this disorder, the specific role of some main redox regulators such as catalase, the main scavenger of H2O2, remains unclear. In the present study, epigastric arteries of kidney transplant recipients, an in vivo model of VC and an in vitro model of VC exhibiting catalase overexpression (Cts) were analyzed. Peri-calcification areas of human epigastric arteries have increased levels of catalase and cytoplasmic rather than nuclear RUNX2. In the in vivo model, advanced aortic VC concurs with lower levels of the H2O2 scavenger, glutathione peroxidase 3 compared to controls. In an early model of calcification using vascular smooth muscle cells (VSMCs), Cts VSMCs showed the expected increase in RUNX2 total levels. However, Cts VMSC also exhibited lower percentage of the nucleus stained for RUNX2 in response to calcifying media. At this early model of VC we did not observe dysregulation of mitochondrial redox state, an increase in general redox state was observed in the cytoplasm. These in vivo and in vitro results highlight the complex role of antioxidant enzymes as catalase in the process of VC by regulation of RUNX2 location.

Anxiety disorders manifest in women more than in men by almost twofold. This narrative review aims to summarize the sex-related biological factors, which underpin anxiety, focusing on the interactions of sex and tryptophan/serotonin with anxiety.A literature search was conducted using Google Scholar, PubMed/MEDLINE, Scopus, and EMBASE databases from inception until December 31, 2017. This review shows that sex may interact with many serotonin functions thereby modulating anxiety, including 5-HT1A and 5-HT2C receptors, 5-HT transporter and central 5-HT concentrations and metabolism. Sex-steroids modulate the expression of serotonin transporter genes, creating a difference in serotonin availability. Sex and estrous cycle phases lead to varying anxiety responses to tryptophan depletion. Testosterone, progesterone and estrogen are important factors in mediating sex differences in serotonin responses to anxiety-generating behavioral tests. At prenatal levels, there are sex-related differences in the reciprocal relationships between serotonin and the HPA-axis, which modulate anxiety-like behaviors. Activated immune-inflammatory pathways induce indoleamine-2,3-dioxynease (IDO) and the tryptophan catabolite (TRYCAT) pathway thereby increasing tryptophan degradation and increasing the production of TRYCATs including kynurenine and quinolinic acid, which may create an overall anxiogenic effect. The effects of immune activation on IDO are significantly more pronounced in women than men and therefore females may show increased levels of anxiogenic TRYCAT following immune challenge. Aberrations in the IDO-activated TRYCAT pathway are found in pregnant females and parturients and are associated with increased anxiety levels in the postnatal period. The results of this review underscore the necessity of studying the associations between serotonin and anxiety in both sexes taking into account the effects of immune activation on IDO and production of anxiogenic TRYCATs. Future anxiety research should focus on the interactions between serotonin/tryptophan and sex, sex hormones, the menstrual cycle, pregnancy, the HPA axis and the immune system through production of anxiogenic TRYCATs.

The cyclic AMP-responsive element-binding protein H (CREBH, encoded by CREB3L3) is a membrane-bound transcriptional factor that primarily localizes in the liver and small intestine. CREBH governs triglyceride metabolism in the liver, which mediates the changes in gene expression governing fatty acid oxidation, ketogenesis, and apolipoproteins upregulating LPL activity. A deficiency of CREBH in mice leads to severe hypertriglyceridemia. CREBH, in synergy with PPARα, has a crucial role in upregulating Fgf21 expression, which is implicated in metabolic homeostasis. CREBH binds to and functions as a co-activator for both PPARα and LXRα in regulating gene expression of lipid metabolism. Furthermore, intestinal CREBH in overexpression reduces cholesterol absorption and suppresses high-cholesterol diet-induced fatty liver. Conversely, a deficiency of CrebH in mice fed on various high-fat diets leads to severe fatty liver. Thus, CREBH could be a therapeutic target in the treatment of metabolic diseases.

Background. Sarcopenia and spinal cord injury (SCI) often coexist, but little is known about the associations of these two pathologies. This study aimed to assess the impact of SCI on muscle and bone mass and the correlations between clinical characteristics of SCI patients and sarcopenia. Methods: 136 patients diagnosed with SCI admitted to rehabilitation hospital were included in the study. The type and severity of injury (AIS), the level of spasticity (MAS), bone mineral density and Appendicular Lean Muscle Mass (ALM) were assessed. Sarcopenia was diagnosed according to the recommended EWGSOP2 cut-off points for ALM. Results: There was a statistically significant association between the ALM value and the gender, 75% of women developing sarcopenia. Among men, 42.9% had sarcopenia. Over 55% of AIS Grades A and B cases had sarcopenia. Mean age of sarcopenic patients was 35.8 years and they had multiple comorbidities. 51.6% of the patients with osteoporosis had sarcopenia. 69.7% of MAS level 0 cases had sarcopenia, while this was diagnosed in about 40% of patients with MAS levels 1-4. Conclusions: Gender, type of injury, presence of multiple comorbidities and age were directly associated with sarcopenia, while surprisingly, spasticity level and the presence of immobilization osteoporosis were not.

Methylation is a biochemical process involving the addition of a methyl group (-CH3) to various chemical compounds. It plays a crucial role in maintaining the homeostasis of the endothelium, which lines the interior surface of blood vessels and has been linked, among other conditions, to coronary artery disease (CAD). Despite significant progress in CAD diagnosis and treatment, intensive research continues into genotypic and phenotypic CAD biomarkers. This review explores the significance of the methylation pathway and folate metabolism in CAD pathogenesis, with a focus on endothelial dysfunction resulting from deficiency in the active form of folate (5-MTHF). We discuss emerging areas of research into CAD biomarkers and factors influencing the methylation process. By highlighting genetically determined methylation disorders, particularly the MTHFR polymorphism, we propose the potential use of the active form of folic acid (5-MTHF) as a novel CAD biomarker and personalized pharmaceutical for selected patient groups. Our aim is to improve the identification of individuals at high risk of CAD and enhance their prognosis.

Parasomnias are a group of sleep disorders characterized by abnormal and unpleasant motor, verbal or behavioral events that occur during sleep or during transitions between wake and sleep states. They disrupt sleep and can have a detrimental impact on the individual experiencing them. Our goal was to identify types of parasomnias and their prevalence in the post-secondary student population and to explore students' coping strategies for parasomnias they found distressing. Seventy-seven post-secondary students completed the 21-item Munich Parasomnia Screening (MUPS) frequency scale. They also rated, on a 10-point scale, how disturbing each parasomnia was. Not only did 92% percent of students report at least one parasomnia, but our results also indicate that the vast majority of students experienced more than one parasomnia. This led us to investigate the likelihood of the co-occurrence of different parasomnias. With respect to the level of subjectively experienced distress, the most prevalent parasomnias were not always the more disturbing ones. Coded open-ended responses about what students do about the disturbing parasomnias indicate that grounding strategies and physical manipulation of one’s body were the most common, although most participants indicated that in spite of distress, they do nothing to cope. In conclusion, our study found a strikingly high prevalence of parasomnias in this sample of young adults and a lack of knowledge about effective means of dealing with these.

Traumatic Brain Injury (TBI) remains a leading cause of morbidity and mortality among all ages; despite the advances, understanding pathophysiological responses after TBI is still complex, involving multiple mechanisms. Previous reviews have focused on potential targets; however, the research on potential targets has continuously grown in the last five years, bringing even more alternatives and elucidating previous mechanisms. Knowing the key and updated pathophysiology concepts is vital for adequate management and better outcomes. This article reviews the underlying molecular mechanisms, the latest updates, and future directions for pathophysiology-based TBI management.

The massive amount of human biological, imaging and clinical data produced by multiple and diverse sources, necessitates integrative modeling approaches able to summarize all this information into answers to specific clinical questions. In this paper, we present a hypermodeling scheme able to combine models of diverse cancer aspects regardless of their underlying method or scale. Describing tissue-scale cancer cell proliferation, biomechanical tumor growth, nutrient transport, genomic-scale aberrant cancer cell metabolism, and cell signaling pathways that regulate the cellular response to therapy, the hypermodel integrates mutation, miRNA expression, imaging, and clinical data. The constituting hypomodels as well as their orchestration and links are described. Two specific cancer types, Wilms tumor (nephroblastoma) and non-small cell lung cancer, are addressed as proof of concept study cases. Personalized simulations over the actual anatomy of a patient have been carried out. The hypermodel has also applied to predict tumor control after radiotherapy and the relationship between tumor proliferative activity and response to neoadjuvant chemotherapy. Our innovative hypermodel holds promise as a digital twin based clinical decision support system and the core of future in silico trial platforms, although additional retrospective adaptation and validation is necessary.

The endothelium is a monolayer of cells lining the inner blood vessels. Endothelial cells (ECs) play indispensable roles in angiogenesis, homeostasis, and immune response under normal physiological conditions, and their dysfunction is closely associated with pathologies such as cardiovascular diseases. Abnormal EC metabolism, especially fatty acid (FA) dysfunctional metabolism, contributes to the development of many diseases including pulmonary hypertension (PH). In this review, we focus on discussing the latest advances in FA metabolism in ECs under normal and pathological conditions with an emphasis on PH. We also highlight areas of research that warrant further investigation.

Autophagy is an essential mechanism to maintain cellular homeostasis. Besides its role in controlling the quality of cytoplasmic components, it participates in nutrient obtaining and lipid mobilization under stressful conditions. Furthermore, autophagy is involved in the regulation of systemic metabolic, a function mainly performed by neuronal populations of the arcuate nucleus of the hypothalamus. Several studies have shown that blockade of autophagy in these neurons can affect central regulation of metabolism and impact body energy balance. Moreover, hypothalamic autophagy can be altered during obesity. However, neurons are not the only cell type involved in the central regulation of metabolism. Astrocytes, essential cells for brain homeostasis, are key metabolic regulators. They can sense metabolic signals in the hypothalamus and modulate systemic functions as glucose homeostasis and feeding response. Moreover, the response of astrocytes to obesity has been widely studied. Astrocytes are important mediators of brain inflammation and can be affected by increased levels of saturated fatty acids associated to obesity. Although autophagy plays important roles for astrocyte homeostasis and functioning, the contribution of astrocyte autophagy to systemic metabolism has not been analysed. Furthermore, how obesity can impact astrocyte autophagy is poorly understood. More studies are needed in other to understand the contribution of astrocyte autophagy to metabolism.

Tandem mass spectrometry (MS/MS) for diagnosing inborn errors of metabolism (IEM) is recognized as an ethical, safe, simple, and reliable screening test. Presented bibliometric analysis aims to describe the network structure of the scientific community in the study area at the level of countries, institutions, authors, papers, keywords, and sources; scientific productivity, directions, and collaboration efforts in a considered period (1991–2023.) Using the PRISMA method, we conducted a systematic search for articles reporting using MS/MS to screen for inherited metabolic disorders and inborn errors of metabolism collected from the Web of Science Core Collection (WOSCC.) A total of 451 articles out of 546, by 2,682 authors, published in 190 journals, with 15,440 citations in 8,181 citing articles, with an average citation of 34.24 per article, and an H-index of 64 were retrieved from the WOSCC. The research status of MS/MS in IEM screening was identified. The most relevant current research directions and future areas of interest were revealed: "selective screening for IEM," "new treatments for IEM," "new disorders considered for MS/MS testing," "ethical issues associated with newborn screening," "new technologies that may be used for newborn screening," "use of a combination of MS/MS and gene sequencing," etc.

Developmental, clinical, and epidemiological research have demonstrated the salience of perceived racial discrimination (PRD) as a contributor to negative mental health outcomes in adolescence. This article summarizes secondary analyses of cross-sectional data from a large-scale youth survey within a predominantly rural state to estimate the prevalence and strength of association between PRD and serious psychological distress, suicidal ideation, and prior suicidal attempts. Data from 93,812 students enrolled in Grades 6, 8, 10, and 12 within 129 school districts across Kentucky were examined to determine prevalence rates for subgroups within the cohort. Logistic regression analyses assessed differences and established comparative strength of association among these variables for racial/ethnic subgroups. PRD was self-reported at high rates across several demographic subgroups and was most evident among Black (24.5%) and Asian (22.1%) students. Multiracial students experienced the highest rates of both SPD and suicidality. Both for the entire cohort and for each racial/ethnic subgroup, PRD was significantly associated with increased likelihood of negative mental health outcomes, although the strength of these associations varied across subgroups and developmental levels. Implications for early intervention and prevention are discussed.

Most neurodegenerative diseases, including Alzheimer's disease, ischemic stroke, subarachnoid hemorrhage, and intracerebral hemorrhage are associated with inflammation. Tumor necrosis factor (TNF) is a pleiotropic pro-inflammatory cytokine that regulates cerebral infarction in stroke pathology, and its action is influenced by the bioavailability of its membrane-bound receptors, TNFR1 and TNFR2, and microglial activation. During the initial onset of these diseases, the soluble variant of the cytokine presents with prolonged and excessive activation of TNFR1, resulting in cell death and long-term neurological impairments. Therapeutic interventions for neurodegenerative diseases have targeted TNF to limit the onset of neuroinflammation. First-generation therapeutics have been demonstrated to inhibit membrane-bound TNF to TNFR2 receptor binding, resulting in severe side effects such as infections and cancer. As such, second-generation drugs, including XPro1595, have been developed to selectively inhibit soluble TNF and impede the effects of TNFR1 while still allowing for TNFR2 activation. Early results in murine TBI models demonstrate reduced glial reactivity by 50%, reduced dendritic degeneration by 30%, increased plasticity by 15%, and improved functional outcomes by 20% post-TBI. This scoping review of TNF receptors in various neurodegenerative diseases seeks to evaluate current and future therapeutic strategies as well as highlight potential strategies to eliminate confounding variables present in the current literature.

Spontaneous splenic rupture (SSR) is a relatively rare, but potentially lethal complication of infectious mononucleosis (IM). While SSR is extremely rare in patients with proven IM, it is the most lethal complication of the infection (9% mortality rate) and can present completely asymptomatically or with abdominal pain and hemodynamic instability. As adolescents and young adults are the most affected population group, with this case report we intend to raise the vigilance of any doctor treating those patients in the emergency department. We present the case of a 16-year-old patient with an atraumatic splenic rupture and hemoperitoneum secondary to an Epstein-Barr virus (EBV) infection. The patient underwent an exploratory laparotomy, and a splenectomy was performed. This case demonstrates that even if the SSR in patients with IM is extremely rare, it should be always considered in a patient with relevant clinical presentation.

Secondary movement disorders (SMDs) represent a heterogeneous group of neurological conditions characterized by abnormal, involuntary movements resulting from various underlying causes. This comprehensive review aims to thoroughly understand SMDs, including their epidemiology, pathophysiology, clinical manifestations, diagnostic approach, and management strategies. SMDs encompass a spectrum of movement abnormalities, including dystonia, chorea, athetosis, myoclonus, tics, and tremors. They can arise from a multitude of etiologies, such as drug-induced effects, post-infectious processes, metabolic disturbances, and structural brain lesions. The epidemiology of SMDs varies depending on the underlying cause, with some conditions being more prevalent in specific populations or age groups. Understanding the pathophysiology of SMDs is crucial for accurate diagnosis and targeted management. Diagnosing SMDs requires a comprehensive approach, including a detailed history, physical examination, laboratory investigations, neuroimaging studies, and sometimes electrophysiological studies. Management of SMDs is multifaceted and may involve pharmacological, non-pharmacological, and surgical interventions. Individualized treatment plans are essential, considering the underlying cause, severity of symptoms, and patient preferences. Emerging concepts in the field of SMDs include advancements in genetic research, identification of biomarkers, and development of novel therapeutic approaches. There is a growing focus on patient-centered care and improving the quality of life for individuals with SMDs. In conclusion, SMDs pose diagnostic and therapeutic challenges, requiring a multidisciplinary approach for optimal management. Continued research and collaboration are essential for advancing our understanding and treatment of these complex disorders.

(1) Background: Grapes and their associated by-products (as grape pomace, GP) stand out for their polyphenol content, which makes them a source of bioactive compounds with antioxidant capacity. The aim of this research was to determine if the inclusion of 50 g/kg of GP in the diet of hens could enrich egg with antioxidants and to study its effect on internal and external egg quality parameters. (2) Methods: A trial was conducted with two genetic lines of hens, which were fed either a control diet or a diet containing 50 g/kg of GP. Performance, internal and external egg quality, and egg yolk content of vitamins E and A, and gallic acid were determined; (3) Results: In eggs laid by hens fed GP diet, Haugh units and yolk colour score were enhanced, and eggshell became thinner, but without affecting the breaking strength. No dietary effect was observed on vitamin contents in yolk. Higher gallic acid content was observed in yolk of eggs laid by hens fed the GP diet, suggesting that some dietary phenolic compounds could be transferred to the eggs. Hen genetics influenced egg weight, albumen Haugh units, shell thickness and α- and γ-tocopherol concentration in yolks; (4) Conclusions: Dietary inclusion of GP improved the internal quality of eggs, enriching yolks with a phenolic compound, but reduced shell thickness.

Cancer is amenable to low-cost treatments, given that it has a significant metabolic component, which can be effected through diet and lifestyle change at minimal cost. The Warburg hypothesis states that cancer cells have altered cell metabolism towards anaerobic glycolysis. Given this metabolic reprogramming in cancer cells, it is possible to target cancers metabolically by depriving them of glucose. In addition to dietary and lifestyle modifications which work on tumors metabolically, there are a panoply of nutritional supplements and repurposed drugs associated with cancer prevention, and better treatment outcomes. These interventions and their evidentiary basis are covered in the latter half of this review to guide future cancer treatment.

Metabolic changes are an important component of tumor cell progression. Tumor cells adapt to environmental stresses via changes to carbohydrate and lipid metabolism. Autophagy, a physiological process in mammalian cells that digests damaged organelles and misfolded proteins via lysosomal degradation is closely associated with metabolism in mammalian cells acting as a meter of cellular ATP levels. In this review, we discuss the changes in glycolytic and lipid biosynthetic pathways in mammalian cells and their impact on carcinogenesis via the autophagy pathway. Also, we discuss the impact of these metabolic pathways on autophagy in lung cancer.

This paper presents a novel improvement of MuSIASEM (Multiscale Integrated Analysis of the Societal and Ecological Metabolism) by incorporating a new regional analysis of the electricity metabolism across levels. An analysis of Mexico illustrates this toolkit and shows that the industry sector had Economic Energy Intensity (EEI) with 40.3 MWh/MMXN reached a higher value than the commerce and services sector with 0.84 MWh/MMXN. Regarding the Economic Labor Productivity (ELP) indicator (AV/h), the industrial sector with 208.5 TMXN/Kh reached a higher value than the Commercial and services sector with 114.3 TMXN/Kh. With reference to the Exosomatic Metabolic Rate (EMR), the Household sector obtained 59.3 KWh/Kh whereas the paid sector reached 2,486.4 KWh/Kh. Disaggregation of the EMR indicator into economic sectors shows that the Industrial sector obtained 8.4 KWh/Kh and the commercial and services sector reached 0.10 KWh/Kh. The lack of complete data for the agricultural sector does not allow us to calculate EEI, ELP, and EMR indicators accurately. Considering the analysis of indicators by regions, regarding the EEI rate, the Central region had the lowest value with 12.7 MWh/MMXN, followed by the Northeast with 21.4 MWh/MMXN and Western with 29.4 MWh/ MMXN, which means that they require less electricity to produce more added value. In terms of the ELP indicator, it was found regions with higher values were Northeast with 182.3 MMXN/Mh, Central with 177.5 MMXN/Mh, and North with 127 MMXN/Mh, which means that these regions produce more added value per hour of work. About the EMR, it is observed that regions in the northern part of the country had higher values: Northwest with 337 KWh/Kh, Baja California Sur with 334 KWh/Kh, Baja California with 328 KWh/Kh, North with 313 KWh/Kh and Northeast with 274 KWh/Kh, which means that these regions consume more electricity per hour. This innovative approach is useful for governance because it helps to understand and reduce asymmetries across regions, resulting in more social equality and a better economic equilibrium across sectors and regions.

Increasing environmental distress is associated with a growing asthma incidence and, with no treatments available, montelukast (MTK) – an antagonist of the cysteinyl leukotrienes receptor 1 – is widely used in the management of symptoms among adults and children. Recently, new molecular targets have been identified and MTK has been proposed for repurposing in other therapeutic applications, with several ongoing clinical trials. The proposed applications include neuroinflammation control, which could be explored in some neurodegenerative disorders, such as Alzheimer’s and Parkinson’s diseases (AD and PD). However, this drug has been associated with an increasing number of reported neuropsychiatric adverse drug reactions. Besides, and despite being on the market since 1998, MTK metabolism is still poorly understood and the mechanisms underlying neuropsychiatric ADRs remain unknown. We review the role of MTK as modulator of leukotriene pathways and systematize the knowledge about MTK metabolism. Known toxic effects of MTK are discussed, and repurposing applications are presented comprehensively, with a focus on AD and PD.

The autonomic regulation of hepatic metabolism offers a novel target for the treatment of non-alcoholic fatty liver disease (NAFLD). However, the molecular characteristics of neurons that regulate the brain-liver axis remain unclear. Since mice lacking neuronal lipoprotein lipase (LPL) develop perturbations in neuronal lipid-sensing and systemic energy balance, we reasoned that LPL might be a component of pre-autonomic neurons involved in the regulation of hepatic metabolism. Here we show that despite obesity, mice with reduced neuronal LPL (NEXCreLPLflox [LPL KD]) show improved glucose tolerance and reduced hepatic lipid accumulation with aging compared to WT controls (LPLflox). To determine the effect of LPL deficiency on neuronal physiology, liver-related neurons were identified in the paraventricular nucleus (PVN) of the hypothalamus using the transsynaptic retrograde tracer PRV-152. Patch-clamp studies revealed reduced inhibitory post-synaptic currents in liver-related neurons of LPL KD mice. Fluorescence Lifetime Imaging Microscopy (FLIM) was used to visualize metabolic changes in LPL-depleted neurons. Quantification of the free vs. bound Nicotinamide Adenine Dinucleotide (NADH) and Flavin Adenine Dinucleotide (FAD) revealed increased glucose utilization and TCA cycle flux in LPL-depleted neurons compared to controls. Global metabolomics from hypothalamic cell lines either deficient in, or over-expressing, LPL recapitulated these findings. Our data suggest that LPL is a novel feature of liver–related preautonomic neurons in the PVN. Moreover, LPL loss is sufficient to cause changes in neuronal substrate utilization and function, which may precede changes in hepatic metabolism.

Growing cells is the typical mode of operation in many aspects of biotechnology and metabolic engineering. This comes about due to cell growth processes creating a driving force that pull metabolic flux along different metabolic pathways, that indirectly help move substrate to product. But, there is an alternative mode of operation that uses resting (non-growing) cells to achieve similar or even higher productivities. In general, resting cells are provided with carbon substrates for biocatalytic reactions but starved of nitrogen or phosphorus. Such resting cells have been usefully employed in many forms of biocatalysis and biotransformation, with or without cofactor regeneration. However, much remains unknown about the transcriptome and metabolome of resting cells in biotransformation settings. This short writeup provides the backdrop of resting cells in biocatalysis, documents their use in biotransformation with application examples, and identifies research gaps that could be filled with contemporary RNA-seq and mass spectrometry proteomics technology. Overall, utility of resting cells in biocatalysis and the extant knowledge gap in their fundamental physiology are highlighted in this resource.

The mosquito microbiota reduces the vector competence of Anopheles to Plasmodium and affects host fitness, it is therefore considered as a potential target to reduce malaria transmission. While immune induction, secretion of antimicrobials and metabolic competition are three typical mechanisms of microbiota-mediated protection against invasive pathogens in mammals, the involvement of metabolic competition or mutualism in mosquito-microbiota and microbiota-Plasmodium interactions has not been investigated. Here, we describe a metabolome analysis of the midgut of An. coluzzii provided with a sugar-meal or a blood-meal, under conventional or antibiotic-treated conditions. We observed that the antibiotic treatment affects the tricarboxylic acid cycle and nitrogen metabolism, notably resulting in decreased abundance of free amino acids. Linking our results with published data, we identified candidate pathways which may participate in microbiota/Plasmodium interactions via metabolic interactions or immune modulation.

The biogeography of inflammation in ulcerative colitis (UC) suggests a proximal to distal concentration gradient of a toxin. Hydrogen sulfide (H2S) has long been considered one such toxin candidate, and dietary sulfur along with the abundance of sulfate reducing bacteria (SRB) were considered the primary determinants of H2S production and clinical course of UC. The metabolic milieu in the lumen of the colon, however, is the result of a multitude of factors beyond dietary sulfur intake and SRB abundance. Here we present an updated formulation of the H2S toxin hypothesis for UC pathogenesis, which strives to incorporate the interdependency of diet composition and the metabolic activity of the entire colon microbial community. Specifically, we suggest that the increasing severity of inflammation along the proximal-to-distal axis in UC is due to dilution of beneficial factors, concentration of toxic factors, and changing detoxification capacity of the host, all of which are intimately linked to the nutrient flow from the diet.

The development of offshore wind farms requires robust bonding solutions that can withstand harsh marine conditions for the easy integration of secondary structures. This paper investigates the durability performance of two adhesives: Sikadur 30 adhesive and Loctite UK 1351 B25 for use in offshore wind environments. Tensile tests on adhesive samples and accelerated aging tests were carried out under a variety of temperature and environmental conditions, including both dry and wet conditions. The long-term effects of aging on adhesive integrity are investigated by simulating the operational life of offshore installations. The evolution of mechanical properties, studied under accelerated aging conditions, provides an important indication of the longevity of structures under normal conditions. The results show significant differences in performance be-tween the two adhesives, highlighting their suitability for specific operating parameters. It should also be noted that for both adhesives, their exposure to different environments (seawater, distilled water, humid climate) over a prolonged period has shown that i) Loctite adhesive has a slightly faster initial uptake than Sikadur adhesive, but the later reaches an asymptotic plateau with a lower maximum absorption rate than Loctite adhesive; and ii) a progressive deterioration in the tensile properties following an exponential function. Therefore, aging behavior results showed a clear correlation with Arrhenius' law, providing a predictive tool for the aging process. Thus, the aging process of the two adhesives follows Arrhenius kinetics.

The work presents a mathematical model of a thermogravimetric curve for the growth and simultaneous sublimation of scale on a metal or alloy surface. Reduction of the reaction area as a result of the formation of oxides of alloying elements (for obtaining the basic oxide) is considered for the alloy. For metals, the case where this area is increased as a result of powder metal crushing is also considered. The equations that were obtained are employed to explain the kinetic curves of the mass change of the samples.

Melatonin, a naturally occurring chemical, has pleiotropic effects across various species. It plays a vital role in animals by regulating the body clock, while in plants, it is known to resist aging. Melatonin is associated with various plant physiological processes, including stress response, plant growth, and flowering time. It has prospects in enhancing and promoting plant growth and development, as well as in strengthening crop yield and increasing sustainability in agriculture. This review summarized the potential roles of melatonin in several plant species, as well as its biosynthetic modes. In addition, we described the recently uncovered melatonin features in plants, summarized the issues and challenges facing plant melatonin research and some feasible solution ideas are proposed.

Hepatitis C virus (HCV) is an oncogenic virus that causes chronic liver disease in more than 80% of patients. During the last decade, efficient direct acting antivirals were introduced into clinical practice. However, clearance of the virus does not reduce risk of end-stage liver diseases to the level observed in patients that have never been infected. So, investigation of HCV pathogenesis is still warranted. Virus-induced changes in cell metabolism contribute to the development of HCV-associated liver pathologies. Here we studied the impact of the virus on the metabolism of polyamines and proline as well as on the urea cycle, which plays a crucial role in liver function. It was found that HCV strongly suppresses the expression of arginase, a key enzyme of the urea cycle, leading to accumulation of arginine and upregulates proline oxidase with a concomitant decrease in proline concentrations. Addition of exogenous proline moderately suppressed viral replication. HCV upregulated transcription but suppressed protein levels of polyamine-metabolizing enzymes. This resulted in a decrease in polyamine content in infected cells. Finally, compounds targeting polyamine metabolism demonstrated pronounced antiviral activity pointing to spermine and spermidine as compounds affecting HCV replication. These data expand our understanding of HCV’s imprint on cell metabolism.

Empowering women and promoting gender equality is crucial for accelerating sustainable development in fragile countries, including the Democratic Republic of Congo (DRC). However, there is scarce existing knowledge or understanding of the factors determining women’s empowerment in these contexts. We aimed to assess women's empowerment and determine its associated factors in Kinshasa, DRC. We analyzed data from the 2021 Performance Monitoring Assessment (PMA) survey. A sample of 1,365 women of childbearing age was retained for this study. Twenty empowerment items related to household decision-making, contraception use, and husband/partner influence were considered. We calculated the average women’s empowerment index (aWEI), identified the women empowerment variables using principal component analysis (PCA), and determined the associated factors for the first three principal components through the performance of multivariate binary logistic regression. In Kinshasa, the overall aWEI was estimated at 0.65. It was low for household decision-making (0.34) and high for husband/partner influence domains (0.93), respectively. Three principal components were identified and named, including the absence of threats, control of sexuality, and participation in decision-making. The factors associated with these components were having internet access, being in free union with a partner, being aged 40-49 years, and residing in a non-slum area. Increasing access to information would enable women in Kinshasa to make strategic decisions about their lives, benefiting themselves and others.

Epidemiological studies point cholesterol as a possible key factor for both prostate cancer incidence and progression. So, it could represent a targetable metabolite as the most aggressive tumors also appear to be sensitive to therapies designed to decrease hypercholesterolemia, such as statins. However, whether and how cholesterol, through its dietary uptake and its metabolism, could be important for early tumorigenesis, remains unknown. Oncogene clonal induction in Drosophila melanogaster accessory gland allows to reproduce tumorigenesis from initiation to early progression, where tumour cells undergo basal extrusion to form extra-epithelial tumors. Here we show that these tumors accumulate lipids, and especially esterified cholesterol, as in human late carcinogenesis. Interestingly, high cholesterol diet displays limited effect on accessory gland tumorigenesis. On the contrary, cell-specific downregulation of cholesterol uptake, intracellular transport or metabolic response, impairs the formation of such tumors. Furthermore, in this context, high cholesterol diet suppresses this impairment. Taken together, these results reveal that during early tumorigenesis, tumour cells strongly increase their uptake and use of dietary cholesterol to specifically promote the step of basal extrusion. Interestingly, expression data from primary prostate cancer tissues indicate an early signature of redirection from cholesterol de novo synthesis to uptake. Altogether, these results suggest by which mechanism reduction of dietary cholesterol could lower the risk and slow down the progression of prostate cancer.