Minimally Invasive Surgical Repair of Simple Congenital Heart Defects Using the Right Vertical Infra-Axillary Thoracotomy Approach.

OBJECTIVE: To evaluate the safety and efficacy of surgical repair for patients diagnosed with simple congenital heart defects (CHD) using the minimally invasive right vertical infra-axillary minithoracotomy (RVIAT) approach. METHODS: We retrospectively reviewed the clinical data of consecutive patients who underwent minimally invasive RVIAT for repair of CHD between August 2019 and August 2022. There were 382 patients who underwent 8 primary procedures and were included in this study. RESULTS: The median age of the patients was 16.2 (interquartile range [IQR], 7.2 to 41.9) months, and the median weight of the patients was 8.8 (IQR, 6.5 to 14) kg. The preoperative diagnoses were as follows: ventricular septal defect, atrial septal defect, partial anomalous pulmonary venous return, partial atrioventricular septal defect, cor triatriatum, complete atrioventricular septal defect, and myxoma. The mean aortic cross-clamp time, bypass time, and operation time were 45.4 ± 19.3 min, 65.6 ± 23.1 min, and 154.5 ± 29.7 min, respectively. There was no in-hospital mortality or conversion to median sternotomy. Two patients (0.5%) required early reoperation; 1 due to postoperative bleeding and 1 for permanent pacemaker implantation. Other complications included trivial residual shunts (23 of 382, 6%), pleural effusion (3 of 382, 0.8%), pneumothorax (0.8%), and wound infection (4 of 382, 1%). There were 2 late noncardiac deaths. Late reoperation was performed on 1 patient with progressive aortic valve regurgitation who required aortic valvuloplasty. CONCLUSIONS: RVIAT is a minimally invasive approach that can be safely performed on patients with simple CHDs. RVIAT may be a good alternative approach for median sternotomy and cardiac intervention.

Secondary metabolites from marine fungus Penicillium chrysogenum VH17 and their antimicrobial and cytotoxic potential.

One new compound, methyl 3-((1-((2-carbamoylphenyl)amino)-1-oxopropan-2-yl)amino)-3-oxopropanoate (1), along with nine known secondary metabolites (2-10) were isolated and elucidated chemical structures from the methanol extract of the marine-derived fungus Penicillium chrysogenum VH17. Subsequent bioassays showed the antimicrobial and cytotoxic potential of the isolated compounds. All compounds 1-10 displayed antimicrobial effects against at least one tested reference microorganism with MIC values ranging from 32 to 256 µg mL-1. Furthermore, compound 4 exhibited significant cytotoxicity against all tested cell lines HepG2, A549, and MCF7 with IC50 values of 29.43 ± 1.37, 33.02 ± 1.53, and 36.72 ± 1.88 µM, respectively, whereas compound 3 exhibited weak cytotoxicity against MCF7 and HepG2 cell lines with IC50 values of 87.17 ± 6.31 and 97.32 ± 5.66 µM, respectively.

High prevalence of adult and nonadult scurvy in an early agricultural transition site from Mainland Southeast Asia was associated with decreased survivorship.

OBJECTIVES: The osteological paradox recognizes that the presence of lesions is not always directly related with increased mortality. When combined with the clinical, historical, and epidemiological literature on scurvy, survivorship analysis, a form of statistical analysis to assess the relationship between the presence of diseases in the archeological record and survival, helps determine the overall burden of the disease both in terms of morbidity and mortality. This article explores the relationship between scurvy and survivorship in 26 adults from Man Bac, a Neolithic site from northern Vietnam together with prepublished evidence of scurvy in the nonadult population (n = 44). METHODS: Diagnosis of scurvy included differential diagnosis combined with the Snoddy, A. M. E., Buckley, H. R., Elliott, G. E., Standen, V. G., Arriaza, B. T., & Halcrow, S. E. (2018). Macroscopic features of scurvy in human skeletal remains: A literature synthesis and diagnostic guide. American Journal of Physical Anthropology, 167(4), 876-895. https://doi.org/10.1002/ajpa.23699 threshold criteria and the Brickley, M. B., & Morgan, B. (2023). Assessing diagnostic certainty for scurvy and rickets in human skeletal remains. American Journal of Biological Anthropology, 181, 637-645 diagnostic certainty approaches. Kaplan-Meier survival curves were produced to assess the relationship between the presence of probable scurvy and age-at-death. RESULTS: The prevalence of probable scurvy in adults (35%) was considerably lower than reported for the nonadults (80%). Almost all lesions observed in the adults were in a mixed stage of healing. Kaplan-Meier analysis demonstrated no difference in survivorship between infants and children (<15 years) with or without probable scurvy, whereas a meaningful difference was observed for the adults and adolescents (15+ years). CONCLUSIONS: The findings demonstrate that scurvy considerably decreased survivorship to older age categories. The degree of lesion remodeling, however, indicates that scurvy was not necessarily the direct cause of death but contributed to an overall disease burden that was ultimately fatal.

Deep learning for autosegmentation for radiotherapy treatment planning: State-of-the-art and novel perspectives.

The rapid development of artificial intelligence (AI) has gained importance, with many tools already entering our daily lives. The medical field of radiation oncology is also subject to this development, with AI entering all steps of the patient journey. In this review article, we summarize contemporary AI techniques and explore the clinical applications of AI-based automated segmentation models in radiotherapy planning, focusing on delineation of organs at risk (OARs), the gross tumor volume (GTV), and the clinical target volume (CTV). Emphasizing the need for precise and individualized plans, we review various commercial and freeware segmentation tools and also state-of-the-art approaches. Through our own findings and based on the literature, we demonstrate improved efficiency and consistency as well as time savings in different clinical scenarios. Despite challenges in clinical implementation such as domain shifts, the potential benefits for personalized treatment planning are substantial. The integration of mathematical tumor growth models and AI-based tumor detection further enhances the possibilities for refining target volumes. As advancements continue, the prospect of one-stop-shop segmentation and radiotherapy planning represents an exciting frontier in radiotherapy, potentially enabling fast treatment with enhanced precision and individualization.

KAT2A and KAT2B prevent double-stranded RNA accumulation and interferon signaling to maintain intestinal stem cell renewal.

Histone acetyltransferases KAT2A and KAT2B are paralogs highly expressed in the intestinal epithelium, but their functions are not well understood. In this study, double knockout of murine Kat2 genes in the intestinal epithelium was lethal, resulting in robust activation of interferon signaling and interferon-associated phenotypes including the loss of intestinal stem cells. Use of pharmacological agents and sterile organoid cultures indicated a cell-intrinsic double-stranded RNA trigger for interferon signaling. Acetyl-proteomics and sequencing of immunoprecipitated double-stranded RNA were used to interrogate the mechanism behind this response, which identified mitochondria-encoded double-stranded RNA as the source of intrinsic interferon signaling. Kat2a and Kat2b therefore play an essential role in regulating mitochondrial functions and maintaining intestinal health.

Modelling the availability of water, energy, and food resources in transboundary river basins to achieve Sustainable Development Goals 2, 6, and 7.

The Water-Energy-Food Nexus (WEFN) has gained international attention as an approach for managing water more holistically, building on the progress made by the Integrated Water Resources Management (IWRM) approach. However, modelling the availability of water, energy, and food and their interconnections is complex, with major barriers that include the availability of both data and modelling platforms capable of assessing the interconnected systems of the WEFN. There have been attempts to model resource availability in each sector generally, but few attempts to consider the WEFN in complex transboundary basins, especially considering Sustainable Development Goals (SDGs). Here, a water, energy, and food availability model was developed using a combination of remotely sensed, national government reported, and global datasets. The model explores the complex interactions between the physical availability and production of water, energy, and food for several subbasins representing different states. Results showed the potential impacts of socioeconomic development, population changes and transboundary cooperation on resources. Transboundary cooperation in the case study Ma Basin in Southeast Asia, under existing resources and operations could improve monthly food security and reduce coal power operations using excess hydropower in the basin during the dry season. These findings show that transboundary cooperation improves access to energy and food, whilst potentially reducing demands for water. Furthermore, the research has highlighted ways in which transboundary cooperation can further assist in attaining SDGs 12 and 13 on responsible production and climate action, respectively. The modelling framework is easily transferable and can support similar analysis in other basins, contributing to global attainment of several SDGs.

Two-channel optical bistability and multistability in a degenerate four-level atomic medium under a static magnetic field.

In this paper, we study the formation of optical bistability (OB) and optical multistability (OM) in a degenerate four-level atomic system by an external magnetic field that is excited by a probe laser field, a coupling laser field and a signal laser field. The coupling field can cause electromagnetically induced transparency (EIT) for the probe field in the atomic medium, while the signal field and/or external magnetic field can switch between single-EIT and two-EIT regimes. Based on these properties, OB and OM effects can be formed at two different frequency regions of the probe field (two channels). By adjusting the magnetic field or the intensity and the frequency of laser fields, the threshold intensity and the width of OB or OM can also be changed simply. The model can be useful for experimental observations and applications in modern photonic devices.

Comparison of Operative and Nonoperative Management of Elderly Fragility Pelvic Ring Fractures.

OBJECTIVES: To compare outcomes of nonoperative and percutaneous fixation of geriatric fragility lateral compression 1 (LC1) pelvic ring fractures. DESIGN: Retrospective. SETTING: Two level 1 trauma centers. PATIENT SELECTION CRITERIA: Included were patients who were 60 years or older with an isolated LC1 pelvic ring fracture managed nonoperatively or those who failed mobilization and were managed operatively with percutaneous sacral fixation. Patients with high-energy mechanisms of injury or polytrauma were excluded. OUTCOME MEASURES AND COMPARISONS: The primary outcome was pain as measured by using the visual analog scale (VAS) after treatment. Secondary outcomes included length of stay, discharge disposition, mortality, readmission rates, and complications. RESULTS: In total, 231 patients were included with a mean age of 79.5 years (range 60-100). One hundred eighty-five (80.0%) patients were female. Sixty-two (26.8%) patients received percutaneous sacral fixation after failed mobilization, and 169 (73.2%) were managed nonoperatively. In the operative group, the median time to surgery was hospital day 4. Nonoperative patients were older (81.5 ± 10.0 years vs. 74.2 ± 9.4 years, P < 0.01) and had a shorter hospital length of stay (4.8 ± 6.2 days) than the operative group (10.6 ± 9.5 days, P < 0.01). Patients in the operative group had more pain (VAS 7.9 ± 3.0) than those in the nonoperative group (VAS 6.6 ± 3.0) ( P = 0.01) on admission but had similar pain control postoperatively (VAS 4.4 ± 3.0) compared with the nonoperative group (VAS 4.5 ± 3.6) on the equivalent hospital day ( P = 0.91). Thus, patients in the operative group experienced more improvement in pain (VAS 3.3 ± 2.7) compared with the nonoperative group (VAS 1.9 ± 3.9) after treatment ( P = 0.02). Ninety-day mortality ( P = 0.21) and readmission rates ( P = 0.27) were similar for both groups. Two patients in the operative cohort sustained nerve injuries, whereas 1 patient in the nonoperative group had a nonunion and underwent surgery. CONCLUSIONS: Patients who undergo percutaneous surgical fixation for low-energy LC1 injuries have similar discharge disposition, mortality, complication rates, and readmission rates compared with patients treated nonoperatively. Percutaneous surgical fixation may provide significant pain relief for patients who failed conservative management. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Aortic Sarcoma Patients With Bone Metastasis.

BACKGROUND: Metastases to the bone of aortic sarcoma include osteolytic and non-osteolytic lesions. This study aims to review the clinical symptoms, the sites and diagnostic methods of bone metastases and to compare the osteolytic and non-osteolytic metastases of patients with aortic sarcoma. METHODS: A systematic search was conducted in PubMed and scientific journals published from 1972 to 2022. Database included reports of aortic sarcomas with bone metastasis published in english and in french. Characteristics of patients were analyzed with Chi-square test or Fisher's exact test between lytic and sclerotic bone metastases. RESULTS: In 29 patients with bone destruction, the symptoms of low back pain and claudication were observed in 10 (34.5%), and 9 cases (31%), respectively. Acute ischemia of the legs and arms accounted for 7 cases (24.1%). There were 4 cases with hypertension (13.8%) and 5 cases with chest pain or abdominal pain or epigastric pain (17.2%). Metastases to the vertebrae, pelvis, femur were observed in 14 (48.3%), 12 (41.4%) and 11 cases (37.9%), respectively. Osteolytic lesions were detected at the time of diagnosis in 16/29 (55.2%) cases. In 27 aortic sarcoma patients with sclerotic bone metastases, symptoms of hypertension were observed in 10 (37.0%), of back pain in 7 (25.9 %), of chest pain or abdominal pain in 5 cases (18.5%). Acute ischemia of the leg occurred in 6 cases (22.2%). Metastases to the vertebrae, bone, pelvis, and femur were observed in 10 (37.0%), 9 (33.3%), 7 (25.9%), and 6 cases (22.2%), respectively. The sign of claudication and methods for detected bone destruction by X-rays were the difference between osteolytic and non-osteolytic metastases of aortic sarcoma (p=0,019; p=0,001), respectively. CONCLUSIONS: Back pain is a common symptom of aortic sarcoma with bone metastasis. The sign of intermittent claudication is the difference between osteolytic and non-osteolytic metastases of aortic sarcoma. Bone destruction occurred in all bones, but mainly in vertebrae, pelvis, femur. Methods for detection of bone destruction mainly by X-rays or CT. Bone destruction was an important sign to detect aortic sarcoma. Sclerotic bone metastases occurred mainly in vertebrae, pelvis, bone and femur. The detection of sclerotic bone metastases based on MRI, PET/CT and autopsy.

Inhibitory Activity of Compounds Isolated from Ligustrum robustum (Roxb.) against HepG2 Liver Cancer Cells: Isocubein and 4-(2-Acetoxyethyl)phenol as Potential Candidates.

Many herbal species in the genus Ligustrum have been shown to contain compounds with anti-cancer biological activity. This study aimed to isolate some compounds from the leaves of Ligustrum robustum (Roxb.) Blume (L. robustum) and evaluate their effects against liver cancer cells. As a result, seven previously reported compounds (1-7) were isolated, including four lignans (1-4) and three phenolic derivatives (5-7). The structures of these compounds were determined using spectroscopic methods and comparison with reported data. All isolates were assessed for their inhibitory effects on HepG2 liver cancer cells. Screening results revealed that two compounds, isocubein (3) and 4-(2-acetoxyethyl)phenol (7), exhibited strong inhibitory activity against cell proliferation, with IC50 values of 3.1±0.9 and 4.5±14 µM, respectively. Further analyses demonstrated that both compounds could suppress the formation and development of 3D tumorspheres in terms of quantity and size. Additionally, isocubein (3) and 4-(2-acetoxyethyl)phenol (7) exhibited the ability to inhibit the migration of HepG2 cells. This study represents the first report on the inhibitory activity against HepG2 liver cancer cells of extracts and isolated compounds from L. robustum, providing valuable information for future research aiming to develop products for liver cancer treatment.

Cognitive dysfunction in diabetes-related foot complications: A cohort study.

Objective: Mild-moderate cognitive impairment has been identified in general diabetes, and early evidence indicates cognitive reductions may be more pronounced in those with diabetes-related foot complications (DRFC). Cognitive difficulties may impede treatment engagement and self-management. This requires further explication to optimise patient care and outcomes. The current study aimed to characterise cognitive function in people with DRFC using comprehensive cognitive measures. Method: This cross-sectional cohort study recruited 80 adult participants (M age = 63.38, SD = 11.40, range = 30 - 89) from the Royal Melbourne Hospital Diabetic Foot Unit in Victoria, Australia, all with DRFC. Each completed a comprehensive cognitive battery (memory, attention, executive functions) and scores were calculated using age-matched population norms, where available. Results: On the majority of tasks, DRFC participants performed significantly worse than age-matched norms, with the largest decrements seen in inhibition control, verbal memory, verbal abstract reasoning and working memory. Small to moderate reductions were also seen in visual learning, verbal fluency, processing speed and premorbid functioning. Demographic (lower education, male gender) and clinical factors (higher HbA1c, macrovascular and microvascular disease, longer diabetes duration) were associated with poorer cognitive functioning. Conclusions: Marked reductions in cognitive functioning were found in individuals with DRFC, predominantly in the domains of verbal memory and executive functioning. Lower education, male gender and indicators of diabetes severity, such as vascular disease, are associated with heightened risk for poorer cognitive functioning. As DRFCs are a serious complication with devastating outcomes if not successfully managed, cognitive barriers to self-management must be addressed to optimise treatment. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-023-01381-4.

Z-number based fuzzy MCDM models for analyzing non-traditional security threats to finance supply chains: A case study from Vietnam.

Non-traditional security (NTS) threats have a vast and profound impact on many aspects of economic, political, social, and many other areas, especially supply chain finance (SCF), particularly in countries like Vietnam, which potentially affects the economic efficiency of businesses' supply chain financial, thereby affecting the general economy of the country and the world. In order to prevent and minimize the negative impacts caused by NTS threats to SCF, this study was conducted to identify NTS threats affecting SCF in Vietnam, at the same time calculate the weight of the impact level and find out the cause and effect relationship between them. Solution strategies are also proposed and ranked, thereby serving as a reference basis for relevant parties to choose appropriate response solutions. Due to the multi-criteria nature of NTS threats, the multiple criteria decision-making (MCDM) method is used in combination with the Z-number concept and Fuzzy set theory to approach the problem of certainty and increase the accuracy of study. The NTS threats are first identified through a literature review and then validated for suitability using the DELPHI technique (DELPHI). Suitable threats will be determined by relationship, weighted by Decision Making Trial And Evaluation Laboratory (DEMATEL) method. Proposed strategies are ranked using the Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS) method. The results indicate that there are 19 NTS factors affecting SCF in Vietnam, and the global economic downturn, pandemic and health crisis, financial crisis and cybersecurity risk are the four root cause factors with the most decisive influence. Businesses and concerns need to prioritize addressing these four threats because they not only have a strong impact but also entail many other threats. The two strategies considered to be the most effective are a sustainable practice and a risk-hedging strategy. Businesses, governments, and stakeholders also should pay attention to the macroeconomic environment, technology, and environment and build sustainable businesses, regularly monitoring economic fluctuations and creating plans to prevent risks.

Preoperative CT Scan is not Associated with Shorter Surgical Time or Improved Patient Outcomes for Trimalleolar Ankle Fractures.

Background: Posterior malleolar involvement can drastically affect patient outcomes. Literature has supported the use of preoperative Computed Tomography (CT) to assess posterior malleolar fracture morphology. The purpose of this study is to determine whether preoperative CT is associated with significant improvement in surgical time, postoperative complications, reoperation rates in trimalleolar ankle fractures. Surgeons were also asked to complete survey regarding use of CT scans to gauge utility preoperatively. Methods: Adult patients with trimalleolar ankle fractures who underwent operative fixation between 2018-2020 were retrospectively reviewed. Primary outcomes included surgical time, postoperative complications, and reoperations. Secondary outcome was presence of posterior malleolar fixation. 15 surgeons who performed ankle ORIF were surveyed to gain information regarding why or why not preoperative CT scan was obtained. Results: 288 patients with trimalleolar ankle fractures were included, 94 had preoperative CT scans (32.6%). No significant differences found in patient age, gender, BMI, smoking status between the groups that did and did not have preoperative CT scan. No significant differences were observed in AO/OTA classification between groups. Average surgical time was significantly higher in group that received a preoperative CT (114 without CT vs. 145 with CT, p<0.05). Complications (10.3% no CT vs 7.4% with CT, p=0.55) and reoperations (6.7% without CT vs. 7.4% with CT, p=0.16) not significantly different between groups. No significant difference was observed in rate of posterior malleolus fixation between groups (43.8% without CT vs 39.4% with CT; p=0.52). Of surveyed surgeons, 87% reported they don't routinely obtain preoperative CT scan for trimalleolar ankle fractures. Most common reasons for preoperative scans were deciding on approach/positioning, assessing for impaction, determining the size of the posterior malleolus. Conclusion: Although preoperative CT scans are obtained in one third of patients with operative trimalleolar ankle fractures, we did not find an improvement in surgical time, complications, and reoperation. Level of Evidence: III.

Knot or not? Identifying unknotted proteins in knotted families with sequence-based Machine Learning model.

Knotted proteins, although scarce, are crucial structural components of certain protein families, and their roles continue to be a topic of intense research. Capitalizing on the vast collection of protein structure predictions offered by AlphaFold (AF), this study computationally examines the entire UniProt database to create a robust dataset of knotted and unknotted proteins. Utilizing this dataset, we develop a machine learning (ML) model capable of accurately predicting the presence of knots in protein structures solely from their amino acid sequences. We tested the model's capabilities on 100 proteins whose structures had not yet been predicted by AF and found agreement with our local prediction in 92% cases. From the point of view of structural biology, we found that all potentially knotted proteins predicted by AF can be classified only into 17 families. This allows us to discover the presence of unknotted proteins in families with a highly conserved knot. We found only three new protein families: UCH, DUF4253, and DUF2254, that contain both knotted and unknotted proteins, and demonstrate that deletions within the knot core could potentially account for the observed unknotted (trivial) topology. Finally, we have shown that in the majority of knotted families (11 out of 15), the knotted topology is strictly conserved in functional proteins with very low sequence similarity. We have conclusively demonstrated that proteins AF predicts as unknotted are structurally accurate in their unknotted configurations. However, these proteins often represent nonfunctional fragments, lacking significant portions of the knot core (amino acid sequence).

Advanced cellulose-based hydrogel TiO2 catalyst composites for efficient photocatalytic degradation of organic dye methylene blue.

Sustainable cellulose-based hydrogels are used in medicine and environmental science. Hydrogels' porosity makes them excellent adsorbents and stable substrates for immobilizing photocatalysts to remove organic dyes. Despite their potential, the implementation of hydrogels for this purpose is still limited due to their high synthesis temperature and low cellulose content. To overcome these challenges, this study develops cellulose-based hydrogels, which have a high cellulose content and can be easily synthesized under ambient conditions. Containing a higher cellulose concentration than previous hydrogels, the synthesized hydrogels are more stable and can be reused numerous times in treatment operations. The hydrogel properties were investigated using Fourier transform infrared spectroscopy, X-ray diffraction and thermal analysis. Scanning electronic microscopy revealed that TiO2 nanoparticles were homogeneously distributed throughout the hydrogel's matrices. In addition, transparent hydrogels allow light to pass through, making them suitable substrates to remove organic dye. The results showed that the hydrogel with TiO2 was able to degrade nearly 90% of organic dye within 180 min. Furthermore, the hydrogel with the embedded catalyst exhibits the potential for reusability with a regeneration efficiency of 80.01% after five runs. These findings suggest that this novel hydrogel is a promising candidate for water pollution remediation.

In situ self-assembly of molybdenum carbide and iron carbide heterostructures on N-doped carbon for an efficient oxygen reduction reaction.

Identifying highly stable, cost-effective, platinum-free, and efficient electrocatalysts for the oxygen reduction reaction (ORR) remains a formidable challenge. The ORR is important for advancing fuel cell and zinc-air battery (ZAB) technologies towards cost-efficiency and environmental sustainability. This work presents the utilization of economically viable materials through a straightforward synthesis process, exhibiting the development of efficient Mo2C/Fe3C-NC catalysts ingeniously derived from phosphomolybdic acid (PMA) and iron phthalocyanine (FePc). The results demonstrate that the optimized Mo2C/Fe3C-NC3 catalysts exhibit remarkable electrochemical performance, evidenced by an impressive onset potential of ∼1.0 V versus RHE, a half-wave potential of 0.89 V, and a superior current density of about 6.2 mA cm-2. As for their performance in ZABs, the optimized catalysts reach a peak power density of 142 mW cm-2 at a current density of 200 mA cm-2. This synergy, coupled with the uniform distribution of Mo2C and Fe3C nanoparticles, greatly enhances the active catalytic sites and promotes electrolyte diffusion. Our approach diverges from traditional methods by employing an in situ self-assembled heterostructure of Mo2C/Fe3C on nitrogen-doped carbon tubes, avoiding the conventional high-temperature hydrogen gas reduction process. Beyond serving as feasible alternatives to commercially available Pt/C catalysts, these materials hold promise for large-scale production owing to their affordability and the simplicity of the synthesis technique. Such a breakthrough paves the way towards the realization of sustainable energy technologies and lays the groundwork for further exploration into amplifying the scalability and efficiency of ORR catalysts.

Discovery of Alkyl Triphenylphosphonium Pinostrobin Derivatives as Potent Anti-Breast Cancer Agents.

Pinostrobin demonstrated anticancer properties, but its hydrophobic feature led to a reduction in bioavailability. The mitochondria-targeted approach successfully synthesized eight new alkyl triphenylphosphonium pinostrobin derivatives (1-8) with good yield in this study. Seven compounds (1-3, 5-8) showed greater cytotoxic potency against the human MCF-7 breast cancer cell line than pinostrobin. Molecular docking studies were performed with two important targets in hormone-dependent anticancer strategies, estrogen receptor α (ERα) ligand binding domains, 3ERT (antagonist recognition and antiproliferative function), and 1GWR (agonist recognition and pro-proliferative function). In addition, the MD simulation study of the two most potent compounds (2 and 3) complexed with both ERα forms suggested that compounds 2 and 3 could serve as favourable antagonists. Furthermore, the in silico ADMET prediction indicated that compounds 2 and 3 could be potential drug candidates.

Rationale and design of a double-blinded, randomized placebo-controlled trial of 40 Hz light neurostimulation therapy for depression (FELIX).

BACKGROUND: Major depressive disorder (MDD) is a debilitating condition that affects more than 300 million people worldwide. Current treatments are based on a trial-and-error approach, and reliable biomarkers are needed for more informed and personalized treatment solutions. One of the potential biomarkers, gamma-frequency (30-80 Hz) brainwaves, are hypothesized to originate from the excitatory-inhibitory interaction between the pyramidal cells and interneurons. The imbalance between this interaction is described as a crucial pathological mechanism in neuropsychiatric conditions, including MDD, and the modulation of this pathological interaction has been investigated as a potential target. Previous studies attempted to induce gamma activity in the brain using rhythmic light and sound stimuli (GENUS - Gamma Entrainment Using Sensory stimuli) that resulted in neuroprotective effects in Alzheimer's disease (AD) patients and animal models. Here, we investigate the antidepressant, cognitive, and electrophysiological effects of the novel light therapy approach using 40 Hz masked flickering light for patients diagnosed with MDD. METHODS AND DESIGN: Sixty patients with a current diagnosis of a major depressive episode will be enrolled in a randomized, double-blinded, placebo-controlled trial. The active treatment group will receive 40 Hz masked flickering light stimulation while the control group will receive continuous light matched in color temperature and brightness. Patients in both groups will get daily light treatment in their own homes and will attend four follow-up visits to assess the symptoms of depression, including depression severity measured by Hamilton Depression Rating Scale (HAM-D17), cognitive function, quality of life and sleep, and electroencephalographic changes. The primary endpoint is the mean change from baseline to week 6 in depression severity (HAM-D6 subscale) between the groups.