Inverse FASN and LDHA correlation drives metabolic resistance in breast cancer.

BACKGROUND: Breast cancer manifests as a heterogeneous pathology marked by complex metabolic reprogramming essential to satisfy its energy demands. Oncogenic signals boost the metabolism, modifying fatty acid synthesis and glucose use from the onset to progression and therapy resistant-forms. However, the exact contribution of metabolic dependencies during tumor evolution remains unclear. METHODS: In this study, we elucidate the connection between FASN and LDHA, pivotal metabolic genes, and their correlation with tumor grade and therapy response using datasets from public repositories. Subsequently, we evaluated the metabolic and proliferative functions upon FASN and LDHA inhibition in breast cancer models. Lastly, we integrated metabolomic and lipidomic analysis to define the contributions of metabolites, lipids, and precursors to the metabolic phenotypes. RESULTS: Collectively, our findings indicate metabolic shifts during breast cancer progression, unvealling two distinct functional energy phenotypes associated with aggressiveness and therapy response. Specifically, FASN exhibits reduced expression in advance-grade tumors and therapy-resistant forms, whereas LDHA demonstrates higher expression. Additionally, the biological and metabolic impact of blocking the enzymatic activity of FASN and LDHA was correlated with resistant conditions. CONCLUSIONS: These observations emphasize the intrinsic metabolic heterogeneity within breast cancer, thereby highlighting the relevance of metabolic interventions in the field of precision medicine.

Novel neutralizing SARS-CoV-2-specific mAbs offer detection of RBD linear epitopes.

BACKGROUND: To stop the spread of the COVID-19 disease, it is crucial to create molecular tools to investigate and diagnose COVID-19. Current efforts focus on developing specific neutralizing monoclonal antibodies (NmAbs) elicited against the receptor-binding domain (RBD). METHODS: In the present study, recombinant RBD (rRBD) protein was produced in E. coli, followed by immunizing mice with purified rRBD. ELISA was applied to screen the hybridomas for positive reactivity with rRBD protein. The linear and conformational epitopes of the mAbs were subsequently identified using western blot. Finally, the reactivity, affinity, and neutralization activity of the purified mAbs were evaluated using ELISA. RESULTS: All mAbs exhibited similar reactivity trends towards both eukaryotic RBD and prokaryotic rRBD in ELISA. Among them, 2E7-D2 and 2B4-G8 mAbs demonstrated higher reactivity than other mAbs. Additionally, in western blot assays, these two mAbs could detect reducing and non-reducing rRBD, indicating recognition of linear epitopes. Notably, five mAbs effectively blocked rRBD- angiotensin-converting enzyme 2 (ACE2) interaction, while two high-affinity mAbs exhibited potent neutralizing activity against eukaryotic RBD. CONCLUSION: In the current study, we generated and characterized new RBD-specific mAbs using the hybridoma technique that recognized linear and conformational epitopes in RBD with neutralization potency. Our mAbs are novel candidates for diagnosing and treating SARS-CoV-2.

Emerging role of lipophagy in liver disorders.

Lipophagy is a selective degradation of lipids by a lysosomal-mediated pathway, and dysregulation of lipophagy is linked with the pathological hallmark of many liver diseases. Downregulation of lipophagy in liver cells results in abnormal accumulation of LDs (Lipid droplets) in hepatocytes which is a characteristic feature of several liver pathologies such as nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Contrarily, upregulation of lipophagy in activated hepatic stellate cells (HSCs) is associated with hepatic fibrosis and cirrhosis. Lipid metabolism reprogramming in violent cancer cells contributes to the progression of liver cancer. In this review, we have summarized the recent studies focusing on various components of the lipophagic machinery that can be modulated for their potential role as therapeutic agents against a wide range of liver diseases.

L-Proline-catalysed synthesis of 2-aryl-2H,5H-thiopyrano[2,3-b] thiochromen-5-ones from 4-hydroxydithiocoumarins and cinnamaldehyde derivatives.

The hitherto unreported synthesis of 2-aryl-2H,5H-thiopyrano[2,3-b]thiochromen-5-one derivatives was achieved from 4-hydroxydithiocoumarin and cinnamaldehyde using 20 mol% L-proline, an environmentally benign organocatalyst in methanol under reflux conditions. The current approach involves imine formation, followed by a Mannich reaction, instead of a 1,4-addition or thia-Michael reaction, and finally, cyclization. The salient features of this method are mild reaction conditions, broad substrate scope, good yield, atom economy, and shorter reaction time.

Hydrocephalus in prematurity: does valve choice make a difference?

PURPOSE: Extremely premature neonates diagnosed with post-haemorrhagic hydrocephalus (PHH) are recognised to have particularly poor outcomes. This study assessed the impact of a number of variables on outcomes in this cohort, in particular the choice of shunt valve mechanism. METHODS: Electronic case notes were retrospectively reviewed of all premature neonates admitted to our centre for management of hydrocephalus between 2012 and 2021. Data included (i) gestational age, (ii) birth weight, (iii) hydrocephalus aetiology, (iv) surgical intervention, (v) shunt system, (vi) 'surgical burden' and (vii) wound failure and infection rate. Data was handled in Microsoft Excel and statistical analysis performed in SPSS v27.0 RESULTS: N = 53 premature hydrocephalic patients were identified (n = 28 (52.8%) female). Median gestational age at birth was 27 weeks (range: 23-36 + 6 weeks), with n = 35 extremely preterm patients and median birth weight of 1.9 kg (range: 0.8-3.6 kg). Total n = 99 programmable valves were implanted (n = 28 (28.3%) de novo, n = 71 (71.2%) revisions); n = 28 (28.3%) underwent n ≥ 1 pressure alterations, after which n = 21 (75%) patients had symptoms improve. In n = 8 patients exchanged from fixed to programmable valves, a mean reduction of 1.9 revisions per patient after exchange was observed (95%CI: 0.36-3.39, p = 0.02). Mean overall shunt survival was 39.5 weeks (95%CI: 30.6-48.5); 33.2 weeks (95%CI: 25.2-41.1) in programmable valves and 35.1 weeks (95%CI: 19.5-50.6) in fixed pressure (p = 0.22) with 12-month survival rates of 25.7% and 24.7%, respectively (p = 0.22). Shorter de novo shunt survival was associated with higher operation count overall (Pearson's R: - 0.54, 95%CI: - 0.72 to - 0.29, p < 0.01). Wound failure, gestational age and birth weight were significantly associated with shorter de novo shunt survival in a Cox regression proportional hazards model; gestational age had the greatest impact on shunt survival (Exp(B): 0.71, 95%CI: 0.63-0.81, p < 0.01). CONCLUSION: Hydrocephalus is especially challenging in extreme prematurity, with a shorter de novo shunt survival associated with higher number of future revisions. Programmable valves provide flexibility with regard to pressure setting, with the potential for fewer shunt revisions in this complex cohort.

Patient-reported outcomes in Primary Spinal Intradural Tumours: a systematic review.

STUDY DESIGN: Systematic review. OBJECTIVES: Primary Spinal Intradural Tumours (PSITs) are rare pathologies that can significantly impact quality of life. This study aimed to review patient reported outcomes (PROs) in PSITs. METHODS: A systematic search of Pubmed and Embase was performed to identify studies measuring PROs in adults with PSITs. PRO results were categorised as relating to Global, Physical, Social, or Mental health. Outcomes were summarised descriptively. RESULTS: Following review of 2382 records, 11 studies were eligible for inclusion (737 patients). All studies assessed surgically treated patients. Schwannoma was the commonest pathology (n = 190). 7 studies measured PROs before and after surgery, the remainder assessed only post-operatively. For eight studies, PROs were obtained within 12 months of treatment. 21 PRO measurement tools were used across included studies, of which Euro-Qol-5D (n = 8) and the pain visual/numerical analogue scale (n = 5) were utilised most frequently. Although overall QoL is lower than healthy controls in PSITs, improvements following surgery were found in Extramedullary tumours (EMT) in overall physical, social, and mental health. Similar improvements were not significant across studies of Intramedullary tumours (IMT). Overall QoL and symptom burden was higher in IMT patients than in brain tumour patients. No studies evaluated the effect of chemotherapy or radiotherapy. CONCLUSION: Patients with PSITs suffer impaired PROs before and after surgery. This is particularly true for IMTs. PRO reporting in PSITs is hindered by a heterogeneity of reporting and varied measurement tools. This calls for the establishment of a standard set of PROs as well as the use of registries.

Antiglycating Effects of Spirulina platensis Aqueous Extract on Glucose-Induced Glycation of Bovine Serum Albumin.

Glucose, the predominant carbohydrate in the human body, initiates nonenzymatic reactions in hyperglycemia, potentially leading to adverse biochemical interactions. This study investigates the interaction between glucose and Bovine Serum Albumin (BSA), along with the protective effects of Spirulina platensis PCC 7345 aqueous extract. Phycobiliproteins (phycocyanin, phycoerythrin, and allophycocyanin) in the extract were quantified using spectrophotometry. The extract's anti-glycation potential was assessed by analyzing its effects on albumin glycation, fluorescent advanced glycation end products (AGEs), thiol group oxidation, and ß-amyloid structure generation. Additionally, its antidiabetic potential was evaluated by measuring α-amylase and α-glucosidase enzyme inhibition. Results indicate that the Spirulina extract significantly mitigated ketoamine levels, fluorescence, and protein-carbonyl production induced by glucose, demonstrating a 67.81 % suppression of AGE formation after 28 days. Moreover, it effectively inhibited amyloid formation in BSA cross-linkages. These findings suggest the potential of S. platensis as an anti-glycation and antidiabetic agent, supporting its consideration for dietary inclusion to manage diabetes and associated complications.

Biochemical and phenological characterization of diverse wheats and their association with drought tolerance genes.

Drought is one of the most important wheat production limiting factor, and can lead to severe yield losses. This study was designed to examine the effect of drought stress on wheat physiology and morphology under three different field capacities (FC) viz. 80% (control), 50% (moderate) and 30% (severe drought stress) in a diverse collection of wheat germplasm including cultivars, landraces, synthetic hexaploid and their derivatives. Traits like grain weight, thousand grain weight and biomass were reduced by 38.23%, 18.91% and 26.47% respectively at 30% FC, whereas the reduction rate for these traits at 50% FC were 19.57%, 8.88% and 18.68%. In principal component analysis (PCA), the first two components PC1 and PC2 accounted for 58.63% of the total variation and separated the cultivars and landraces from synthetic-based germplasm. Landraces showed wide range of phenotypic variations at 30% FC compared to synthetic-based germplasm and improved cultivars. However, least reduction in grain weight was observed in improved cultivars which indicated the progress in developing drought resilient cultivars. Allelic variations of the drought-related genes including TaSnRK2.9-5A, TaLTPs-11, TaLTPs-12, TaSAP-7B-, TaPPH-13, Dreb-B1 and 1fehw3 were significantly associated with the phenological traits under drought stress in all 91 wheats including 40 landraces, 9 varieties, 34 synthetic hexaploids and 8 synthetic derivatives. The favorable haplotypes of 1fehw3, Dreb-B1, TaLTPs-11 and TaLTPs-12 increased grain weight, and biomass. Our results iterated the fact that landraces could be promising source to deploy drought adaptability in wheat breeding. The study further identified drought tolerant wheat genetic resources across various backgrounds and identified favourable haplotypes of water-saving genes which should be considered to develop drought tolerant varieties.

Water stress effects on stay green and chlorophyll fluorescence with focus on yield characteristics of diverse bread wheats.

MAIN CONCLUSION: The study provided an insight toward better understanding of stay-green mechanisms for drought tolerance improvement and identified that synthetic-derived wheats proved as a promising germplasm for improved tolerance against water stress. Stay-green (SG) trait is considered to be related with the ability of wheat plants to maintain photosynthesis and CO2 assimilation. The present study explored the interaction of water stress with SG expression through physio-biochemical, agronomic and phenotypic responses among diverse wheat germplasm comprising of 200 synthetic hexaploids, 12 synthetic derivatives, 97 landraces and 16 conventional bread wheat varieties, for 2 years. The study established that variation of SG trait existed in the studied wheat germplasm and there was positive association between SG trait and tolerance to water stress. The relationship of SG trait with chlorophyll content (r = 0.97), ETR (r = 0.28), GNS (r = 0.44), BMP (r = 0.34) and GYP (r = 0.44) was particularly promising under water stress environment. Regarding chlorophyll fluorescence, the positive correlation of фPSII (r = 0.21), qP (r = 0.27) and ETR (r = 0.44) with grain yield per plant was noted. The improved ΦPSII and Fv/Fm of PSII photochemistry resulted in the high photosynthesis activity in SG wheat genotypes. Regarding relative water content and photochemical quenching coefficient, synthetic-derived wheats were better by maintaining 20.9, 9.8 and 16.1% more RWC and exhibiting 30.2, 13.5 and 17.9% more qP when compared with landraces, varieties and synthetic hexaploids, respectively, under water stress environment. Synthetic derived wheats also exhibited relatively more SG character with good yield and were more tolerant to water stress in terms of grain yield, grain weight per plant, better photosynthetic performance through chlorophyll fluorescence measurement, high leaf chlorophyll and proline content, and hence, may be used as novel sources for breeding drought tolerant materials. The study will further facilitate research on wheat leaf senescence and will add to better understanding of SG mechanisms for drought tolerance improvement.

FASN multi-omic characterization reveals metabolic heterogeneity in pancreatic and prostate adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) and prostate cancer (PCa) are among the most prevalent malignant tumors worldwide. There is now a comprehensive understanding of metabolic reprogramming as a hallmark of cancer. Fatty acid synthase (FASN) is a key regulator of the lipid metabolic network, providing energy to favor tumor proliferation and development. Whereas the biological role of FASN is known, its response and sensitivity to inhibition have not yet been fully established in these two cancer settings. METHODS: To evaluate the association between FASN expression, methylation, prognosis, and mutational profile in PDAC and PCa, we interrogated public databases and surveyed online platforms using TCGA data. The STRING database was used to investigate FASN interactors, and the Gene Set Enrichment Analysis platform Reactome database was used to perform an enrichment analysis using data from RNA sequencing public databases of PDAC and PCa. In vitro models using PDAC and PCa cell lines were used to corroborate the expression of FASN, as shown by Western blot, and the effects of FASN inhibition on cell proliferation/cell cycle progression and mitochondrial respiration were investigated with MTT, colony formation assay, cell cycle analysis and MitoStress Test. RESULTS: The expression of FASN was not modulated in PDAC compared to normal pancreatic tissues, while it was overexpressed in PCa, which also displayed a different level of promoter methylation. Based on tumor grade, FASN expression decreased in advanced stages of PDAC, but increased in PCa. A low incidence of FASN mutations was found for both tumors. FASN was overexpressed in PCa, despite not reaching statistical significance, and was associated with a worse prognosis than in PDAC. The biological role of FASN interactors correlated with lipid metabolism, and GSEA indicated that lipid-mediated mitochondrial respiration was enriched in PCa. Following validation of FASN overexpression in PCa compared to PDAC in vitro, we tested TVB-2640 as a FASN inhibitor. PCa proliferation arrest was modulated by FASN inhibition in a dose- and time-dependent manner, whereas PDAC proliferation was not altered. In line with this finding, mitochondrial respiration was found to be more affected in PCa than in PDAC. FASN inhibition interfered with metabolic signaling causing lipid accumulation and affecting cell viability with an impact on the replicative processes. CONCLUSIONS: FASN exhibited differential expression patterns in PDAC and PCa, suggesting a different evolution during cancer progression. This was corroborated by the fact that both tumors responded differently to FASN inhibition in terms of proliferative potential and mitochondrial respiration, indicating that its use should reflect context specificity.

Discovery of a novel marker for human granulocytes and tissue macrophages: RTL1 revisited.

Here, retrotransposon-like 1 (RTL1) is introduced as a marker for circulating and tissue neutrophils, tissue macrophages, and tumor-associated macrophages (TAM) and neutrophils (TAN). Anti-RTL1 polyclonal and monoclonal antibodies were produced, and their reactivity was examined by Western blotting (WB), ELISA, and immunostaining of human normal and cancer tissues. The reactivity of the anti-RTL1 antibodies with peripheral blood leukocytes and a panel of hematopoietic cell lines was examined. The generated antibodies specifically detected RTL1 in the WB of the placenta and U937 cells. The polyclonal antibody showed excellent reactivity with tissue-resident macrophages, Hofbauer cells, alveolar and splenic macrophages, Kupffer cells, and inflammatory cells in the tonsil, appendix, and gallbladder. In vitro GM-CSF-differentiated macrophages also showed a high level of intracellular RTL1 expression. TAM and TAN also showed excellent reactivity with this antibody. Almost all circulating granulocytes but not lymphocytes or monocytes expressed RTL1 at their surface. Serial sections of the appendix stained with CD15 and RTL1 and placenta stained with CD68 and RTL1 showed a considerable overlap in RTL1 expression in CD15+ granulocytes and CD68+ macrophages. A small percentage of myelomonocytic cell lines was positive for surface RTL1, while promyelocytic, monocytic, megaloblastic, and lymphoblastic cell lines were negative. Endothelial cells of normal and cancer tissues highly expressed RTL1. RTL1 could be considered a new marker for different normal tissue macrophages, TAM, circulating and tissue neutrophils, and TAN.

Network modeling of major depressive disorder symptoms in adult women.

BACKGROUND: Major depressive disorder (MDD) is one of the growing human mental health challenges facing the global health care system. In this study, the structural connectivity between symptoms of MDD is explored using two different network modeling approaches. METHODS: Data are from 'the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders (VATSPSUD)'. A cohort of N = 2163 American Caucasian female-female twins was assessed as part of the VATSPSUD study. MDD symptoms were assessed using personal structured clinical interviews. Two network analyses were conducted. First, an undirected network model was estimated to explore the connectivity between the MDD symptoms. Then, using a Bayesian network, we computed a directed acyclic graph (DAG) to investigate possible directional relationships between symptoms. RESULTS: Based on the results of the undirected network, the depressed mood symptom had the highest centrality value, indicating its importance in the overall network of MDD symptoms. Bayesian network analysis indicated that depressed mood emerged as a plausible driving symptom for activating other symptoms. These results are consistent with DSM-5 guidelines for MDD. Also, somatic weight and appetite symptoms appeared as the strongest connections in both networks. CONCLUSIONS: We discuss how the findings of our study might help future research to detect clinically relevant symptoms and possible directional relationships between MDD symptoms defining major depression episodes, which would help identify potential tailored interventions. This is the first study to investigate the network structure of VATSPSUD data using both undirected and directed network models.

Incidence of diabetic ketoacidosis during COVID-19 pandemic: a meta-analysis of 124,597 children with diabetes.

BACKGROUND: Diabetic ketoacidosis (DKA) is a potentially life-threatening complication of type 1 diabetes mellitus (T1DM) that has increased during the COVID-19 pandemic. This study will not only shed light on such life-threatening complications but also be a step to increase the awareness of healthcare providers about such complications in the upcoming pandemic waves and increased dependence on telemedicine. Thus, we aimed to further investigate the increase of DKA in pediatrics. METHODS: PubMed, Web of Science, and Scopus were broadly searched for studies assessing the incidence of DKA in pediatrics during the COVID-19 pandemic. RESULTS: Our study included 24 papers with a total of 124,597 children with diabetes. A statistically significant increase occurred in the risk of DKA among newly diagnosed T1DM patients during the pandemic (RR 1.41; 95% CI 1.19, 1.67; p < 0.01; I2 = 86%), especially in the severe form of DKA (RR 1.66: 95% CI 1.3, 2.11) when compared to before. CONCLUSION: DKA in newly diagnosed children with T1DM has increased during the pandemic and presented with a severe form. This may reflect that COVID-19 may have contributed not only to the development but also the severity of DKA. IMPACT: Diabetic ketoacidosis (DKA) is a life-threatening complication of type 1 diabetes mellitus (T1DM) that has increased during the COVID-19 pandemic. Our study included 25 papers with a total of 124,597 children with diabetes. A statistically significant increase occurred in the risk of DKA among newly diagnosed T1DM patients during the pandemic. Our findings reflect that COVID-19 may have an altered presentation in T1DM and can be related to DKA severity.

Cow's Milk-related Symptom Score for cow's milk allergy assessment: a meta-analysis for test accuracy.

BACKGROUND: We aimed to assess the ability of Cow's Milk-related Symptom Score (CoMiss) in screening cow's milk protein allergy (CMPA) and assess validation of its sensitivity and specificity. METHODS: We searched the PubMed, WOS, Embase, and Ovid databases using broad terms and keywords for the concepts of the symptom-based score (CoMiss) and cow's milk allergy. We performed the meta-analyses using a meta-package of R software and Meta-DiSc software. RESULTS: Fourteen studies were included with a total of 1238 children. At cut-off value 12, CoMiss had a pooled sensitivity of 0.64 and a pooled specificity of 0.75. The PLR and NLR were 3.05 and 0.5, respectively. The AUC value of the sROC curve was 0.7866. CoMiss showed a significant difference in CMPA patients at baseline and after milk elimination for 2-4 weeks (MD, 7.18), as well as between the CMPA-positive group compared with the CMPA-negative group, however, the statistical significancy was obtained after leave study of Selbuz et al. out of the analysis (MD, 4.61). CONCLUSIONS: CoMiss may be a promising symptom score in the Awareness of the symptoms related to cow's milk allergy and a useful tool in monitoring the response to a cow's milk-free diet. IMPACT: Cow's milk protein allergy (CMPA) is the most frequent food allergy in children under the age of 3 years. Cow's Milk-related Symptom Score (CoMiss) is a clinical scoring system to assist primary healthcare providers in early detection of CMPA We performed a meta-analysis of CoMiss test accuracy. Our findings reflect that CoMiss may be a promising symptom score in CMPA awareness and a useful tool in monitoring the response to a cow's milk-free diet.

Advanced methods of algal pigments extraction: A review.

Algae are exclusively aquatic photosynthetic organisms that are microscopic or macroscopic, unicellular or multicellular and distributed across the globe. They are a potential source of food, feed, medicine and natural pigments. A variety of natural pigments are available from algae including chlorophyll a, b, c d, phycobiliproteins, carotenes and xanthophylls. The xanthophylls include acyloxyfucoxanthin, alloxanthin, astaxanthin, crocoxanthin, diadinoxanthin, diatoxanthin, fucoxanthin, loroxanthin, monadoxanthin, neoxanthin, nostoxanthin, perdinin, Prasinoxanthin, siphonaxanthin, vaucheriaxanthin, violaxanthin, lutein, zeaxanthin, ß-cryptoxanthin, while carotenes include echinenone, α-carotene, ß-carotene, γ-carotene, lycopene, phytoene, phytofluene. These pigments have applications as pharmaceuticals and nutraceuticals and in the food industry for beverages and animal feed production. The conventional methods for the extraction of pigments are solid-liquid extraction, liquid-liquid extraction and soxhlet extraction. All these methods are less efficient, time-consuming and have higher solvent consumption. For a standardized extraction of natural pigments from algal biomass advanced procedures are in practice which includes Supercritical fluid extraction, Pressurized liquid extraction, Microwave-assisted extraction, Pulsed electric field, Moderate electric field, Ultrahigh pressure extraction, Ultrasound-assisted extraction, Subcritical dimethyl ether extraction, Enzyme assisted extraction and Natural deep eutectic solvents. In the present review, these methods for pigment extraction from algae are discussed in detail.

Cottonseed oil: A review of extraction techniques, physicochemical, functional, and nutritional properties.

Seed oils are the richest source of vitamin-E-active compounds, which contribute significantly to antioxidant activities. Cottonseed oil (CS-O) is attaining more consideration owing to its high fiber content and stability against auto-oxidation. CS-O has gained a good reputation in the global edible oil market due to its distinctive fatty acid profile, anti-inflammatory, and cardio-protective properties. CS-O can be extracted from cottonseed (CS) by microwave-assisted extraction (MAE), aqueous/solvent extraction (A/SE), aqueous ethanol extraction (A-EE), subcritical water extraction, supercritical carbon dioxide extraction (SC-CO2), and enzyme-assisted extraction (E-AE). In this review, the importance, byproducts, physicochemical characteristics, and nutritional profile of CS-O have been explained in detail. This paper also provides a summary of scientific studies existing on functional and phytochemical characteristics of CS-O. Its consumption and health benefits are also deliberated to discover its profitability and applications. CS-O contains 26-35% saturated, 42-52% polyunsaturated, and 18-24% monounsaturated FA. There is approximately 1000 ppm of tocopherols in unprocessed CS-O, but up to one-third is lost during processing. Moreover, besides being consumed as cooking oil, CS-O discovers applications in many fields such as biofuel, livestock, cosmetics, agriculture, and chemicals. This paper provides a comprehensive review of CS-O, its positive benefits, fatty acid profile, extraction techniques, and health applications.HighlightsCS-O is a rich source of exceptional fatty acids.Various techniques to extract the CS-O are discussed.Numerous physicochemical properties of CS-O for the potential market are assessed.It has a wide range of functional properties.Nutritional quality and health benefits are also evaluated.

Effects of Reductive Soil Disinfestation Combined with Liquid-Readily Decomposable Compounds and Solid Plant Residues on the Bacterial Community and Functional Composition.

Reductive soil disinfestation (RSD) incorporated with sole plant residues or liquid-readily decomposable compounds is an effective management strategy to improve soil health. However, the synthetic effects of RSD incorporated with liquid-readily decomposable compounds and solid plant residues on soil ecosystem services remain unclear. Field experiments were carried out to investigate the effects of untreated soil (CK), RSD incorporated with sawdust (SA), molasses (MO), and their combinations (SA + MO) on the bacterial community and functional composition. The results showed that RSD treatments significantly altered soil bacterial community structure compared to CK treatment. The bacterial community structure and composition in MO and SA + MO treatments were clustered compared to SA treatment. This was mainly attributed to the readily decomposable carbon sources in molasses having a stronger driving force to reshape the soil microbial community during the RSD process. Furthermore, the functional compositions, such as the disinfestation efficiency of F. oxysporum (96.4 - 99.1%), abundances of nitrogen functional genes, soil metabolic activity, and functional diversity, were significantly increased in all of the RSD treatments. The highest disinfestation efficiency and abundances of denitrification (nirS and nrfA) and nitrogen fixation (nifH) genes were observed in SA + MO treatment. Specifically, SA + MO treatment enriched more abundant beneficial genera, e.g., Oxobacter, Paenibacillus, Cohnella, Rummeliibacillus, and Streptomyces, which were significantly and positively linked to disinfestation efficiency, soil metabolic activity, and denitrification processes. Our results indicated that combining RSD practices with liquid-readily decomposable compounds and solid plant residues could effectively improve soil microbial community and functional composition.

Deciphering the Synergies of Reductive Soil Disinfestation Combined with Biochar and Antagonistic Microbial Inoculation in Cucumber Fusarium Wilt Suppression Through Rhizosphere Microbiota Structure.

Application of reductive soil disinfestation (RSD), biochar, and antagonistic microbes have become increasingly popular strategies in a microbiome-based approach to control soil-borne diseases. The combined effect of these remediation methods on the suppression of cucumber Fusarium wilt associated with microbiota reconstruction, however, is still unknown. In this study, we applied RSD treatment together with biochar and microbial application of Trichoderma and Bacillus spp. in Fusarium-diseased cucumbers to investigate their effects on wilt suppression, soil chemical changes, microbial abundances, and the rhizosphere communities. The results showed that initial RSD treatment followed by biochar amendment (RSD-BC) and combined applications of microbial inoculation and biochar (RSD-SQR-T37-BC) decreased nitrate concentration and raised soil pH, soil organic carbon (SOC), and ammonium in the treated soils. Under RSD, the applications of Bacillus (RSD-SQR), Trichoderma (RSD-T37), and biochar (RSD-BC) suppressed wilt incidence by 26.8%, 37.5%, and 32.5%, respectively, compared to non-RSD treatments. Moreover, RSD-SQR-T37-BC and RSD-T37 caused greater suppressiveness of Fusarium wilt and F. oxysporum by 57.0 and 33.5%, respectively. Rhizosphere beta diversity and alpha diversity revealed a difference between RSD-treated and non-RSD microbial groups. The significant increase in the abundance, richness, and diversity of bacteria, and the decrease in the abundance and diversity of fungi under RSD-induced treatments attributed to the general suppression. Identified bacterial (Bacillus, Pseudoxanthomonas, Flavobacterium, Flavisolibacter, and Arthrobacter) and fungal (Trichoderma, Chaetomium, Cladosporium, Psathyrella, and Westerdykella) genera were likely the potential antagonists of specific disease suppression for their significant increase of abundances under RSD-treated soils and high relative importance in linear models. This study infers that the RSD treatment induces potential synergies with biochar amendment and microbial applications, resulting in enhanced general-to-specific suppression mechanisms by changing the microbial community composition in the cucumber rhizosphere.

FeCl3-catalyzed regioselective ring-opening of aryl oxirane with 4-hydroxycoumarin for the synthesis of furo[3,2-c]coumarins.

The regioselective ring-opening of aryl oxiranes was investigated with various 4-hydroxycoumarins in dimethyl sulfoxide in the presence of 20 mol% FeCl3 as a catalyst at 110 °C. This approach provided a short and concise synthetic route for the regioselective synthesis of 2-aryl-4H-furo[3,2-c] coumarin derivatives. Product formation occurred through regioselective ring-opening of the aryl oxirane at a less hindered site, followed by dehydration and concomitant cyclization. The salient features of our protocol were: cost-effectiveness; short reaction time; step- and atom economy; easy handling; broad scope of substrates; regioselectivity; good-to-excellent yields; non-requirement of dry solvents, co-catalysts, ligands, or any other additives; inert atmospheric conditions.

Predicting cholangiocarcinoma in primary sclerosing cholangitis: using artificial intelligence, clinical and laboratory data.

BACKGROUND: Primary sclerosing cholangitis (PSC) patients have a risk of developing cholangiocarcinoma (CCA). Establishing predictive models for CCA in PSC is important. METHODS: In a large cohort of 1,459 PSC patients seen at Mayo Clinic (1993-2020), we quantified the impact of clinical/laboratory variables on CCA development using univariate and multivariate Cox models and predicted CCA using statistical and artificial intelligence (AI) approaches. We explored plasma bile acid (BA) levels' predictive power of CCA (subset of 300 patients, BA cohort). RESULTS: Eight significant risk factors (false discovery rate: 20%) were identified with univariate analysis; prolonged inflammatory bowel disease (IBD) was the most important one. IBD duration, PSC duration, and total bilirubin remained significant (p < 0.05) with multivariate analysis. Clinical/laboratory variables predicted CCA with cross-validated C-indexes of 0.68-0.71 at different time points of disease, significantly better compared to commonly used PSC risk scores. Lower chenodeoxycholic acid, higher conjugated fraction of lithocholic acid and hyodeoxycholic acid, and higher ratio of cholic acid to chenodeoxycholic acid were predictive of CCA. BAs predicted CCA with a cross-validated C-index of 0.66 (std: 0.11, BA cohort), similar to clinical/laboratory variables (C-index = 0.64, std: 0.11, BA cohort). Combining BAs with clinical/laboratory variables leads to the best average C-index of 0.67 (std: 0.13, BA cohort). CONCLUSIONS: In a large PSC cohort, we identified clinical and laboratory risk factors for CCA development and demonstrated the first AI based predictive models that performed significantly better than commonly used PSC risk scores. More predictive data modalities are needed for clinical adoption of these models.