Miracle-dz/UniFAR-FTUs huggingface dataset:
Violaxanthin and Zeaxanthin May Replace Lutein at the L1 Site of LHCII, Conserving the Interactions with Surrounding Chlorophylls and the Capability of Triplet–Triplet Energy Transfer

Carotenoids represent the first line of defence of photosystems against singlet oxygen (1O2) toxicity, because of their capacity to quench the chlorophyll triplet state (3Chl) through a physical mechanism based on the transfer of triplet excitation (triplet–triplet energy transfer, TTET). In previous works, we showed that the antenna LHCII is characterised by a robust photoprotective mechanism, able to adapt to the removal of individual chlorophylls while maintaining a remarkable capacity for 3Chl quenching. In this work, we investigated the effects on this quenching induced in LHCII by the replacement of the lutein bound at the L1 site with violaxanthin and zeaxanthin. We studied LHCII isolated from the Arabidopsis thaliana mutants lut2—in which lutein is replaced by violaxanthin—and lut2 npq2, in which all xanthophylls are replaced constitutively by zeaxanthin. We characterised the photophysics of these systems via optically detected magnetic resonance (ODMR) and time-resolved electron paramagnetic resonance (TR-EPR). We concluded that, in LHCII, lutein-binding sites have conserved characteristics, and ensure efficient TTET regardless of the identity of the carotenoid accommodated.
Evaluation of a Gel Containing a Propionibacterium Extract in an In Vivo Model of Wound Healing

Inappropriate wound healing (WH) management can cause significant comorbidities, especially in patients affected by chronic and metabolic diseases, such as diabetes. WH involves several different, partially overlapping processes, including hemostasis, inflammation, cell proliferation, and remodeling. Oxidative stress in WH contributes to WH impairment because of the overexpression of radical oxygen species (ROS) and nitrogen species (RNS). This study aimed to evaluate the in vitro antioxidative action of a gel containing a Propionibacterium extract (Emorsan® Gel) and assess its skin re-epithelialization properties in a mouse model of WH. The scavenging effects of the bacterial extract were assessed in vitro through the ABTS and DPPH assays and in L-929 murine fibroblasts. The effects of the Emorsan® Gel were studied in vivo in a murine model of WH. After WH induction, mice were treated daily with vehicle or Emorsan® Gel for 6 or 12 days. According to the in vitro tests, the Propionibacterium extract exerted an inhibitory effect on ROS and RNS, consequently leading to the reduction in malondialdehyde (MDA) and nitrite levels. Before proceeding with the in vivo study, the Emorsan® Gel was verified to be unabsorbed. Therefore, the observed effects could be ascribed to a local action. The results obtained in vivo showed that through local reduction of oxidative stress and inflammation (IL-1β, TNF-α), the Emorsan® Gel significantly reduced the infiltration of mast cells into the injured wound, leading to the amelioration of symptoms such as itch and skin irritation. Therefore, the Emorsan® Gel improved the speed and percentage of wound area closure by improving the tissue remodeling process, prompting vascular–endothelial growth factor (VEGF) and transforming growth factor (TGF)- β production and reducing the expression of adhesion molecules. Emorsan® Gel, by its ability to inhibit free radicals, could reduce local inflammation and oxidative stress, thus enhancing the speed of wound healing.
Potential Values of Circulating microRNA-21 to Predict Early Recurrence in Patients with Colorectal Cancer after Treatments

Insufficient prognosis of local recurrence contributes to the poor progression-free survival rate and death in colorectal cancer (CRC) patients. Various biomarkers have been explored in predicting CRC recurrence. This study investigated the expressions of plasma/exosomal microRNA-21 (miR-21) in 113 CRC patients by qPCR, their values of predicting CRC recurrence, and the possibility to improve the prognostic efficacy in early CRC recurrence in stratified patients by combined biomarkers including circulating miR-21s, circulating tumour cells/microemboli (CTCs/CTM), and serum carcinoembryonic antigen (CEA)/carbohydrate antigen 19-9 (CA19-9). Expressions of plasma and exosomal miR-21s were significantly correlated (p < 0.0001) in all and late-stage patients, presenting similar correlations with other biomarkers. However, stage IV patients stratified by a high level of exosomal miR-21 and stage I to III patients stratified by a high level of plasma miR-21 displayed significantly worse survival outcomes in predicting CRC recurrence, suggesting their different values to predict CRC recurrence in stratified patients. Comparable and even better performances in predicting CRC recurrence in late-stage patients were found by CTCs/CTM from our blood samples as sensitive biomarkers. Improved prognosing efficacy in CRC recurrence and better outcomes to significantly differentiate recurrence in stratified patients could be obtained by analysing combined biomarkers.
The Performance of HE4 Alone and in Combination with CA125 for the Detection of Ovarian Cancer in an Enriched Primary Care Population

Simple Summary Ovarian cancer is the most common cause of death from gynaecological cancer in the UK. Survival is better when the disease is diagnosed early. However, identifying ovarian cancer is challenging because symptoms are non-specific. Simple, accurate tests are needed to help identify ovarian cancer in symptomatic women. HE4, a relatively new blood biomarker, has shown promise in the hospital setting. This study aimed to assess whether HE4 would improve ovarian cancer diagnosis in women with symptoms in primary care. We found combining HE4 levels with the currently used test (CA125) within an algorithm (Risk of Ovarian Malignancy Algorithm) improved the detection of ovarian cancer in primary care, particularly in women under 50 years of age, where diagnosis is more challenging. However, our results require validation in a larger sample. This study advances our knowledge of HE4 as an ovarian cancer biomarker in the primary care setting. Abstract Human epididymis 4 (HE4) is a promising ovarian cancer biomarker, but it has not been evaluated in primary care. In this prospective observational study, we investigated the diagnostic accuracy of HE4 alone and in combination with CA125 for the detection of ovarian cancer in symptomatic women attending primary care. General practitioner (GP)-requested CA125 samples were tested for HE4 at a large teaching hospital in Manchester, and cancer outcomes were tracked for 12 months. We found a low incidence of ovarian cancer in primary care; thus, the cohort was enriched with pre-surgical samples from 81 ovarian cancer patients. The Risk of Ovarian Malignancy Algorithm (ROMA) was calculated using age (51) as a surrogate for menopause. Conventional diagnostic accuracy metrics were determined. A total of 1229 patients were included; 82 had ovarian cancer. Overall, ROMA performed best (AUC-0.96 (95%CI: 0.94–0.98, p = <0.001)). In women under 50 years, the combination of CA125 and HE4 (either marker positive) was superior (sensitivity: 100% (95%CI: 81.5–100.0), specificity: 80.1% (95%CI 76.7–83.1)). In women over 50, ROMA performed best (sensitivity: 84.4% (95%CI: 73.1–92.2), specificity: 87.2% (95%CI 84.1–90)). HE4 and ROMA may improve ovarian cancer detection in primary care, particularly for women under 50 years, in whom diagnosis is challenging. Validation in a larger primary care cohort is required.
B7-H4 Immune Checkpoint Protein Affects Viability and Targeted Therapy of Renal Cancer Cells

Targeted therapy in combination with immune checkpoint inhibitors has been recently implemented in advanced or metastatic renal cancer treatment. However, many treated patients either do not respond or develop resistance to therapy, making alternative immune checkpoint-based immunotherapies of potential clinical benefit for specific groups of patients. In this study, we analyzed the global expression of B7 immune checkpoint family members (PD-L1, PD-L2, B7-H2, B7-H3, B7-H4, B7-H5, B7-H6, and B7-H7) in human renal cancer cells (Caki-1, A-498, and 786-O cell lines) upon treatment with clinically relevant targeted drugs, including tyrosine kinase inhibitors (Axitinib, Cabozantinib, and Lenvatinib) and mTOR inhibitors (Everolimus and Temsirolimus). Gene expression analysis by quantitative PCR revealed differential expression patterns of the B7 family members in renal cancer cell lines upon targeted drug treatments. B7-H4 gene expression was upregulated after treatment with various targeted drugs in Caki-1 and 786-O renal cancer cells. Knocking down the expression of B7-H4 by RNA interference (RNAi) using small interfering RNA (siRNA) decreased renal cancer cell viability and increased drug sensitivity. Our results suggest that B7-H4 expression is induced upon targeted therapy in renal cancer cells and highlight B7-H4 as an actionable immune checkpoint protein in combination with targeted therapy in advanced renal cancer cases resistant to current treatments.
Meibomian Gland Density: An Effective Evaluation Index of Meibomian Gland Dysfunction Based on Deep Learning and Transfer Learning

We aimed to establish an artificial intelligence (AI) system based on deep learning and transfer learning for meibomian gland (MG) segmentation and evaluate the efficacy of MG density in the diagnosis of MG dysfunction (MGD). First, 85 eyes of 85 subjects were enrolled for AI system-based evaluation effectiveness testing. Then, from 2420 randomly selected subjects, 4006 meibography images (1620 upper eyelids and 2386 lower eyelids) graded by three experts according to the meiboscore were analyzed for MG density using the AI system. The updated AI system achieved 92% accuracy (intersection over union, IoU) and 100% repeatability in MG segmentation after 4 h of training. The processing time for each meibography was 100 ms. We discovered a significant and linear correlation between MG density and ocular surface disease index questionnaire (OSDI), tear break-up time (TBUT), lid margin score, meiboscore, and meibum expressibility score (all p < 0.05). The area under the curve (AUC) was 0.900 for MG density in the total eyelids. The sensitivity and specificity were 88% and 81%, respectively, at a cutoff value of 0.275. MG density is an effective index for MGD, particularly supported by the AI system, which could replace the meiboscore, significantly improve the accuracy of meibography analysis, reduce the analysis time and doctors’ workload, and improve the diagnostic efficiency.
The Nuclear Pore Complex: Birth, Life, and Death of a Cellular Behemoth

Nuclear pore complexes (NPCs) are the only transport channels that cross the nuclear envelope. Constructed from ~500–1000 nucleoporin proteins each, they are among the largest macromolecular assemblies in eukaryotic cells. Thanks to advances in structural analysis approaches, the construction principles and architecture of the NPC have recently been revealed at submolecular resolution. Although the overall structure and inventory of nucleoporins are conserved, NPCs exhibit significant compositional and functional plasticity even within single cells and surprising variability in their assembly pathways. Once assembled, NPCs remain seemingly unexchangeable in post-mitotic cells. There are a number of as yet unresolved questions about how the versatility of NPC assembly and composition is established, how cells monitor the functional state of NPCs or how they could be renewed. Here, we review current progress in our understanding of the key aspects of NPC architecture and lifecycle.
Outcome and Prognostic Factors of COVID-19 Infection in Swiss Cancer Patients: Final Results of SAKK 80/20 (CaSA)

Simple Summary The characterization of clinical outcomes and prognostic factors in COVID-19-infected cancer patients is important for health care authorities, policy makers and oncologists. We collected extensive data on COVID-19-infected cancer patients from 1 March 2020 over a one-year period. Among 455 patients included, death from COVID-19 infection occurred in 98 patients, resulting in a mortality rate of 21.5%. Age ≥ 65 years, non-curative disease, intensive care unit admission and oxygen requirement were particular and independent negative prognostic factors for death from COVID-19. COVID-19 severity and mortality in cancer patients remained high in a country (Switzerland) with a decentralized, high-quality, universal-acess health care system. Abstract Purpose: These are the final results of a national registry on cancer patients with COVID-19 in Switzerland. Methods: We collected data on symptomatic COVID-19-infected cancer patients from 23 Swiss sites over a one-year period starting on 1 March 2020. The main objective was to assess the outcome (i.e., mortality, rate of hospitalization, ICU admission) of COVID-19 infection in cancer patients; the main secondary objective was to define prognostic factors. Results: From 455 patients included, 205 patients (45%) had non-curative disease, 241 patients (53%) were hospitalized for COVID-19, 213 (47%) required oxygen, 43 (9%) invasive ventilation and 62 (14%) were admitted to the ICU. Death from COVID-19 infection occurred in 98 patients, resulting in a mortality rate of 21.5%. Age ≥65 years versus <65 years (OR 3.14, p = 0.003), non-curative versus curative disease (OR 2.42, p = 0.012), ICU admission (OR 4.45, p < 0.001) and oxygen requirement (OR 20.28, p < 0.001) were independently associated with increased mortality. Conclusions: We confirmed high COVID-19 severity and mortality in real-world cancer patients during the first and second wave of the pandemic in a country with a decentralized, high-quality, universal-access health care system. COVID-19-associated mortality was particularly high for those of older age in a non-curative disease setting, requiring oxygen or ICU care.
Divergent Roles of Mitochondria Dynamics in Pancreatic Ductal Adenocarcinoma

Simple Summary Pancreatic ductal adenocarcinoma is one of the most lethal neoplasia due to the lack of early diagnostic markers and effective therapies. The study of metabolic alterations of PDAC is of crucial importance since it would open the way to the discovery of new potential therapies. Mitochondria represent key organelles that regulate energy metabolism, and they remodel their structure by undergoing modifications by fusing with other mitochondria or dividing to generate smaller ones. The alterations of mitochondria arrangement may influence the metabolism of PDAC cells, thus supporting the proliferative needs of cancer. Shedding light on this topic regarding cancer and, more specifically, PDAC may help identify new potential strategies that hit cancer cells at their “core,” i.e., mitochondria. Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive tumors; it is often diagnosed at an advanced stage and is hardly treatable. These issues are strictly linked to the absence of early diagnostic markers and the low efficacy of treatment approaches. Recently, the study of the metabolic alterations in cancer cells has opened the way to important findings that can be exploited to generate new potential therapies. Within this scenario, mitochondria represent important organelles within which many essential functions are necessary for cell survival, including some key reactions involved in energy metabolism. These organelles remodel their shape by dividing or fusing themselves in response to cellular needs or stimuli. Interestingly, many authors have shown that mitochondrial dynamic equilibrium is altered in many different tumor types. However, up to now, it is not clear whether PDAC cells preferentially take advantage of fusion or fission processes since some studies reported a wide range of different results. This review described the role of both mitochondria arrangement processes, i.e., fusion and fission events, in PDAC, showing that a preference for mitochondria fragmentation could sustain tumor needs. In addition, we also highlight the importance of considering the metabolic arrangement and mitochondria assessment of cancer stem cells, which represent the most aggressive tumor cell type that has been shown to have distinctive metabolic features to that of differentiated tumor cells.
Nutritional Quality, Antioxidant, Microstructural and Sensory Properties of Spontaneously Fermented Gluten-Free Finger Millet Biscuits

Finger millet (FM) is a nutritious and gluten-free cereal grain which is rich in dietary fibre, minerals and antioxidant properties, thereby making it an ideal raw material for preparing gluten-free foods for people suffering from celiac disease. Spontaneous fermentation of FM grains has shown improved nutritional and functional properties of its flour and can be used as a functional ingredient for gluten free biscuits. The aim of this study was to determine the effect of spontaneous fermentation (SF) on the nutritional quality, antioxidant, microstructural, and sensory characteristics of gluten-free FM biscuits obtained from light and dark brown FM flours. Results showed that SF decreased ash, crude fibre, and crude fat contents as well as total phenolic and flavonoids contents. Protein content, carbohydrates content, energy values, antioxidant activity (DPPH and FRAP), and mineral content of FM biscuits increased due to SF. The colour properties such as lightness (L*), showed a significant increase as SF period increased in light brown FM biscuits, however dark brown FM biscuits showed no significant difference. The hue angle and colour differences (ΔE) of FM biscuits increased with the increasing period of SF, ranging from 43.20 to 53.76° and from 0.67 to 7.96, respectively. Spontaneous fermentation also decreased physical properties of biscuits such as diameter (4.76 to 4.54 cm), weight (12.77 to 11.99 g), and spread ratio (7.25 to 6.05), while an increase in thickness and hardness was noted. Spontaneous fermentation also induced changes on the microstructure of FM biscuits. Among the fermented biscuits, panelists preferred 24 h gluten-free fermented FM biscuits since they had better sensory properties. Overall, SF enhanced the nutritional value and health promoting compounds of gluten-free FM biscuits.
Primary Aldosteronism and Resistant Hypertension: A Pathophysiological Insight

Primary aldosteronism (PA) is a pathological condition characterized by an excessive aldosterone secretion; once thought to be rare, PA is now recognized as the most common cause of secondary hypertension. Its prevalence increases with the severity of hypertension, reaching up to 29.1% in patients with resistant hypertension (RH). Both PA and RH are “high-risk phenotypes”, associated with increased cardiovascular morbidity and mortality compared to non-PA and non-RH patients. Aldosterone excess, as occurs in PA, can contribute to the development of a RH phenotype through several mechanisms. First, inappropriate aldosterone levels with respect to the hydro-electrolytic status of the individual can cause salt retention and volume expansion by inducing sodium and water reabsorption in the kidney. Moreover, a growing body of evidence has highlighted the detrimental consequences of “non-classical” effects of aldosterone in several target tissues. Aldosterone-induced vascular remodeling, sympathetic overactivity, insulin resistance, and adipose tissue dysfunction can further contribute to the worsening of arterial hypertension and to the development of drug-resistance. In addition, the pro-oxidative, pro-fibrotic, and pro-inflammatory effects of aldosterone may aggravate end-organ damage, thereby perpetuating a vicious cycle that eventually leads to a more severe hypertensive phenotype. Finally, neither the pathophysiological mechanisms mediating aldosterone-driven blood pressure rise, nor those mediating aldosterone-driven end-organ damage, are specifically blocked by standard first-line anti-hypertensive drugs, which might further account for the drug-resistant phenotype that frequently characterizes PA patients.
Atomic layer deposition process modeling and experimental investigation for sustainable manufacturing of nano thin films

This paper studies the adverse environmental impacts of atomic layer deposition (ALD) nano-manufacturing technology on ALD of Al2O3 nano-scale thin films. Numerical simulations with detailed ALD surface reaction mechanism developed based on Density Functional Theory (DFT), and atomic-level calculations are performed to investigate the effects of four process parameters including process temperature, pulse time, purge time, and carrier gas flow rate on ALD film deposition rate, process emissions and wastes. Full-cycle ALD simulations reveal that the depositions of nano-thin-films in ALD are in essence the chemisorption of the gaseous species and the conversion of surface species. Methane emissions are positively proportional to the film deposition process. The studies show that process temperature fundamentally affects the ALD chemical process by changing the energy states of the surface species. Pulse time is directly related to the precursor dosage. Purge time influences the ALD process by changing the gas-surface interaction time, and higher carrier gas flow rate alters the ALD flow field by accelerating the convective heat and mass transfer in ALD process.
A Cross-Sectional Study on the Relationship between Oral Function and Sarcopenia in Japanese Patients with Regular Dental Maintenance

We aimed to clarify the relationship between oral function assessments regarding oral hypofunction and sarcopenia in patients who had completed treatment for organic dental problems, including oral pain, removable denture fit, and tooth loss. This cross-sectional study included 269 patients aged ≥65 years (mean age 74.9 ± 6.50 years, 133 men, 136 women) who visited a dental clinic between June 2019 and March 2021. We evaluated oral function and sarcopenia and analyzed their relationship using the Jonckheere–Terpstra test, Mantel–Haenszel trend test, and Poisson regression analysis. We diagnosed 132 (49.07%) patients with oral hypofunction, 30 (11.2%) with sarcopenia, and 24 (8.9%) with severe sarcopenia. The number of oral hypofunction items (prevalence rate ratio [PRR] = 1.39, 95%Wald = 0.11 to 0.56) was significantly associated with sarcopenia. For each of the items, tongue-lip motor function [ta] (PRR = 0.80, 95%Wald = −0.44 to −0.02)] [ka] (PRR = 0.76, 95%Wald = −0.53 to −0.03) and tongue pressure (PRR = 0.95, 95%Wald = −0.09 to −0.02) showed a significant association with sarcopenia. However, no significant association was found for other variables. Dentists should not only treat organic dental problems but also consider the relationship between oral function and sarcopenia.