Sex reporting of cells used in cancer research: A systematic review.

Sex and gender disparities in biomedical research have been emphasized to improve scientific knowledge applied for the health of both men and women. Despite sex differences in cancer incidence, prognosis, and responses to therapeutic agents, mechanistic explanations at molecular levels are far from enough. Recent studies suggested that cell sex is an important biological variable due to differences in sex chromosome gene expression and differences in events associated with developmental biology. The objective of this study was to analyze the reporting of sex of cells used in cancer research using articles published in Cancer Cell, Molecular Cancer, Journal of Hematology & Oncology, Journal for ImmunoTherapy of Cancer, and Cancer Research in 2020, and to examine whether there exists any sex bias. We found that the percentage of cells with sex notation in the article was 36.5%. Primary cells exhibited higher sex notation compared to cell lines. A higher percentage of female cells were used in cell cultures with sex notation. Also, sex-common cells omitted sex description more often compared to sex-specific cells. None of the cells isolated from embryo and esophagus reported the cell sex in the article. Our results indicate cell sex report in cancer research is limited to a small proportion of cells used in the study. These results call for acknowledging the sex of cells to increase the applicability of biomedical research discoveries.

The dopamine analogue CA140 alleviates AD pathology, neuroinflammation, and rescues synaptic/cognitive functions by modulating DRD1 signaling or directly binding to Abeta.

BACKGROUND: We recently reported that the dopamine (DA) analogue CA140 modulates neuroinflammatory responses in lipopolysaccharide-injected wild-type (WT) mice and in 3-month-old 5xFAD mice, a model of Alzheimer's disease (AD). However, the effects of CA140 on Aß/tau pathology and synaptic/cognitive function and its molecular mechanisms of action are unknown. METHODS: To investigate the effects of CA140 on cognitive and synaptic function and AD pathology, 3-month-old WT mice or 8-month-old (aged) 5xFAD mice were injected with vehicle (10% DMSO) or CA140 (30 mg/kg, i.p.) daily for 10, 14, or 17 days. Behavioral tests, ELISA, electrophysiology, RNA sequencing, real-time PCR, Golgi staining, immunofluorescence staining, and western blotting were conducted. RESULTS: In aged 5xFAD mice, a model of AD pathology, CA140 treatment significantly reduced Aß/tau fibrillation, Aß plaque number, tau hyperphosphorylation, and neuroinflammation by inhibiting NLRP3 activation. In addition, CA140 treatment downregulated the expression of cxcl10, a marker of AD-associated reactive astrocytes (RAs), and c1qa, a marker of the interaction of RAs with disease-associated microglia (DAMs) in 5xFAD mice. CA140 treatment also suppressed the mRNA levels of s100ß and cxcl10, markers of AD-associated RAs, in primary astrocytes from 5xFAD mice. In primary microglial cells from 5xFAD mice, CA140 treatment increased the mRNA levels of markers of homeostatic microglia (cx3cr1 and p2ry12) and decreased the mRNA levels of a marker of proliferative region-associated microglia (gpnmb) and a marker of lipid-droplet-accumulating microglia (cln3). Importantly, CA140 treatment rescued scopolamine (SCO)-mediated deficits in long-term memory, dendritic spine number, and LTP impairment. In aged 5xFAD mice, these effects of CA140 treatment on cognitive/synaptic function and AD pathology were regulated by dopamine D1 receptor (DRD1)/Elk1 signaling. In primary hippocampal neurons and WT mice, CA140 treatment promoted long-term memory and dendritic spine formation via effects on DRD1/CaMKIIα and/or ERK signaling. CONCLUSIONS: Our results indicate that CA140 improves neuronal/synaptic/cognitive function and ameliorates Aß/tau pathology and neuroinflammation by modulating DRD1 signaling in primary hippocampal neurons, primary astrocytes/microglia, WT mice, and aged 5xFAD mice.

Sialylated IVIg promotes clinical improvements in a rabbit dry eye model by regulating inflammatory cytokines.

Dry eye disease (DED) is caused by a loss of homeostasis of the tear film, which results in visual disturbance, ocular surface inflammation and damage, and neurosensory abnormalities. Although it is prevalent in 5-50% of the global population, there are limited clinical options for its treatment. This study explored the potential use of human intravenous immunoglobulin (IVIg) and its enriched fractions of sialylation, sialylated IVIg (sIVIg), as a treatment for DED. Fifteen female New Zealand white rabbits were topically instilled with 0.2% benzalkonium chloride (BAC) twice daily for five consecutive days to induce experimental dry eye. Saline, 0.4% IVIg, or 0.04% sIVIg eye drops were instilled twice daily for 20 consecutive days. Clinical evaluations, such as non-invasive tear break-up time (NIBUT) and corneal fluorescein staining (CFS), were conducted. mRNA levels of mucin 4, mucin 16, TNF-α, IL-1ß, MMP9, IL-10, TGF-ß, and CD209 in rabbit conjunctival tissues were examined using reverse transcription polymerase chain reaction (RT-PCR) or quantitative RT-PCR (qRT-PCR). The relationships between CD209 family members in rabbits and various mammalian species were analyzed using a phylogenetic tree. IVIg or sIVIg treatment resulted in clinical improvements in the rabbit DED model. The inflammatory cytokines, TNF-α and IL-1ß, were increased and mucin 4 and mucin 16, cell surface-associated mucins, were decreased in BAC-induced dry eye. Following IVIg or sIVIg treatment, inflammatory cytokines decreased, whereas the anti-inflammatory cytokine, IL-10, increased substantially. Moreover, a 10-fold lower sIVIg treatment dose resulted in prolonged IL-10 production, representing a significantly improved DED compared to IVIg. Furthermore, the expression of rabbit CD209 mRNA in the rabbit conjunctiva and its close relationship with primate homologs suggest that it may interact with IVIg or sIVIg to promote IL-10 expression, as previously described in humans. At a lower dosage, sIVIg showed a more efficient improvement in DED, making it a promising new candidate medication for DED.

Performance of ChatGPT-3.5 and GPT-4 in national licensing examinations for medicine, pharmacy, dentistry, and nursing: a systematic review and meta-analysis.

BACKGROUND: ChatGPT, a recently developed artificial intelligence (AI) chatbot, has demonstrated improved performance in examinations in the medical field. However, thus far, an overall evaluation of the potential of ChatGPT models (ChatGPT-3.5 and GPT-4) in a variety of national health licensing examinations is lacking. This study aimed to provide a comprehensive assessment of the ChatGPT models' performance in national licensing examinations for medical, pharmacy, dentistry, and nursing research through a meta-analysis. METHODS: Following the PRISMA protocol, full-text articles from MEDLINE/PubMed, EMBASE, ERIC, Cochrane Library, Web of Science, and key journals were reviewed from the time of ChatGPT's introduction to February 27, 2024. Studies were eligible if they evaluated the performance of a ChatGPT model (ChatGPT-3.5 or GPT-4); related to national licensing examinations in the fields of medicine, pharmacy, dentistry, or nursing; involved multiple-choice questions; and provided data that enabled the calculation of effect size. Two reviewers independently completed data extraction, coding, and quality assessment. The JBI Critical Appraisal Tools were used to assess the quality of the selected articles. Overall effect size and 95% confidence intervals [CIs] were calculated using a random-effects model. RESULTS: A total of 23 studies were considered for this review, which evaluated the accuracy of four types of national licensing examinations. The selected articles were in the fields of medicine (n = 17), pharmacy (n = 3), nursing (n = 2), and dentistry (n = 1). They reported varying accuracy levels, ranging from 36 to 77% for ChatGPT-3.5 and 64.4-100% for GPT-4. The overall effect size for the percentage of accuracy was 70.1% (95% CI, 65-74.8%), which was statistically significant (p < 0.001). Subgroup analyses revealed that GPT-4 demonstrated significantly higher accuracy in providing correct responses than its earlier version, ChatGPT-3.5. Additionally, in the context of health licensing examinations, the ChatGPT models exhibited greater proficiency in the following order: pharmacy, medicine, dentistry, and nursing. However, the lack of a broader set of questions, including open-ended and scenario-based questions, and significant heterogeneity were limitations of this meta-analysis. CONCLUSIONS: This study sheds light on the accuracy of ChatGPT models in four national health licensing examinations across various countries and provides a practical basis and theoretical support for future research. Further studies are needed to explore their utilization in medical and health education by including a broader and more diverse range of questions, along with more advanced versions of AI chatbots.

The role of Savings and Internal Lending Communities (SILCs) in improving community-level household wealth, financial preparedness for birth, and utilization of reproductive health services in rural Zambia: a secondary analysis.

BACKGROUND: Savings and Internal Lending Communities (SILCs) are a type of informal microfinance mechanism widely adapted in Zambia. The benefits of SILCs paired with other interventions have been studied in many countries. However, limited studies have examined SILCs in the context of maternal health. This study examined the association between having access to SILCs and: 1) household wealth, 2) financial preparedness for birth, and 3) utilization of various reproductive health services (RHSs). METHODS: Secondary analysis was conducted on baseline and endline household survey data collected as part of a Maternity Waiting Home (MWH) intervention trial in 20 rural communities across seven districts of Zambia. Data from 4711 women who gave birth in the previous year (baseline: 2381 endline: 2330) were analyzed. The data were stratified into three community groups (CGs): CG1) communities with neither MWH nor SILC, CG2) communities with only MWH, and CG3) communities with both MWH and SILC. To capture the community level changes with the exposure to SILCs, different women were randomly selected from each of the communities for baseline and endline data, rather than same women being surveyed two times. Interaction effect of CG and timepoint on the outcome variables - household wealth, saving for birth, antenatal care visits, postnatal care visits, MWH utilization, health facility based delivery, and skilled provider assisted delivery - were examined. RESULTS: Interaction effect of CGs and timepoint were significantly associated only with MWH utilization, health facility delivery, and skilled provider delivery. Compared to women from CG3, women from CG1 had lower odds of utilizing MWHs and delivering at health facility at endline. Additionally, women from CG1 and women from CG2 had lower odds of delivering with a skilled provider compared to women from CG3. CONCLUSION: Access to SILCs was associated with increased MWH use and health facility delivery when MWHs were available. Furthermore, access to SILCs was associated with increased skilled provider delivery regardless of the availability of MWH. Future studies should explore the roles of SILCs in improving the continuity of reproductive health services. TRIAL REGISTRATION: NCT02620436.

Molineria recurvata Ameliorates Streptozotocin-Induced Diabetic Nephropathy through Antioxidant and Anti-Inflammatory Pathways.

Molineria recurvata (MR) has been traditionally used to manage diabetes mellitus in India. However, the molecular mechanism of MR on the diabetic-induced nephropathy has not been clearly investigated. Thus, this study investigates the protective effects of the MR extract on nephropathy in streptozotocin (STZ)-induced diabetic rats. Diabetes was instigated by a single intraperitoneal injection of STZ (45 mg/kg) in male Sprague-Dawley rats. Once the diabetes was successfully induced, the MR extract (200 mg/kg/day) or metformin (200 mg/kg/day) was orally administered for 14 days. Renal function, morphology changes and levels of inflammatory cytokines were measured. Blood glucose concentrations were considerably reduced in STZ-induced diabetic rats following treatment with the MR extract. The administration of the MR extract substantially restored the abnormal quantity of the oxidative DNA damage marker 8-hydroxy-2'-deoxy-guanosine (8-OHdG), malondialdehyde, glutathione, oxidized glutathione, superoxide dismutase, catalase, interleukin (IL)-1ß, IL-6, IL-10, and transforming growth factor-ß (TGF-ß). The urinary excretion of kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), selenium binding protein 1 (SBP1), and pyruvate kinase M2 (PKM2) was significantly reduced in diabetes rats after administration of the MR extracts. In the kidneys of STZ-induced diabetic rats, the MR extracts markedly downregulated the expression of fibronectin, collagen-1, and α-smooth muscle actin (α-SMA). In particular, the MR extracts markedly increased the level of SIRT1 and SIRT3 and reduced claudin-1 in the kidney. These results suggest that the MR extracts exhibits therapeutic activity in contrast to renal injury in STZ-induced diabetic rats through repressing inflammation and oxidative stress.

O-GlcNAcylation regulates dopamine neuron function, survival and degeneration in Parkinson disease.

The dopamine system in the midbrain is essential for volitional movement, action selection, and reward-related learning. Despite its versatile roles, it contains only a small set of neurons in the brainstem. These dopamine neurons are especially susceptible to Parkinson's disease and prematurely degenerate in the course of disease progression, while the discovery of new therapeutic interventions has been disappointingly unsuccessful. Here, we show that O-GlcNAcylation, an essential post-translational modification in various types of cells, is critical for the physiological function and survival of dopamine neurons. Bidirectional modulation of O-GlcNAcylation importantly regulates dopamine neurons at the molecular, synaptic, cellular, and behavioural levels. Remarkably, genetic and pharmacological upregulation of O-GlcNAcylation mitigates neurodegeneration, synaptic impairments, and motor deficits in an animal model of Parkinson's disease. These findings provide insights into the functional importance of O-GlcNAcylation in the dopamine system, which may be utilized to protect dopamine neurons against Parkinson's disease pathology.

Effect of gintonin on matrix metalloproteinase-9 concentration in tears during corneal wound healing in rabbits.

It has been shown that gintonin, isolated from Panax ginseng, can promote rapid corneal wound healing. We aimed to elucidate the underlying mechanism and investigated whether gintonin affects the concentration of the extracellular matrix remodelling factor matrix metalloproteinase-9 (MMP-9) in tears during rabbit corneal wound healing in vivo. Twelve eyes (six rabbits) were divided equally into three groups. All eyes underwent corneal de-epithelialisation. The control group received Tearin Free sodium hyaluronate 0.1%, the solcoseryl group received solcoseryl-120 concentrate, and the gintonin group received 2.5 mg gintonin in sodium hyaluronate 0.1%. All preparations were administered for 5 days and the concentration of MMP-9 was measured in tears via ELISA on days 0, 1, and 5. MMP-9 concentrations in all groups were increased at day 1 and reduced at day 5. Of note, we found a significant change over the time frame for the gintonin group (P < 0.05) but not for the control or solcoseryl groups (P > 0.05) Moreover, increased MMP-9 levels between days 0 and 1, and their reduction between days 1 and 5, were significant in the gintonin group compared to those in the other groups (P < 0.05); however, and once more, these changes were not significant between the control and solcoseryl groups (P > 0.05). In conclusion, gintonin increases the concentration of MMP-9 rapidly within a day of injury, and decreasing it thereafter.

Slice-selective learning for Alzheimer's disease classification using a generative adversarial network: a feasibility study of external validation.

PURPOSE: The aim of this feasibility study was to use slice selective learning using a Generative Adversarial Network for external validation. We aimed to build a model less sensitive to PET imaging acquisition environment, since differences in environments negatively influence network performance. To investigate the slice performance, each slice evaluation was performed. METHODS: We trained our model using a 18F-fluorodeoxyglucose ([18F]FDG) PET/CT dataset obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database and tested the model with a Severance Hospital dataset. We applied slice selective learning to reduce computational cost and to extract unbiased features. We extracted features of Alzheimer's disease (AD) and normal cognitive (NC) condition using a Boundary Equilibrium Generative Adversarial Network (BEGAN) for stable convergence. Then, we utilized these features to train a support vector machine (SVM) classifier to distinguish AD from NC. RESULTS: The slice range that covered the posterior cingulate cortex (PCC) using double slices showed the best performance. The accuracy, sensitivity, and specificity of our proposed network was 94.33%, 91.78%, and 97.06% using the Severance dataset and 94.82%, 92.11%, and 97.45% using the ADNI dataset. The performance on the two independent datasets showed no statistical difference (p > 0.05). Moreover, there was a statistical difference in the performance between using two slices and one slice as input (p < 0.05). CONCLUSIONS: Our model learned the generalized features of AD and NC for external validation when appropriate slices were selected. This study showed the feasibility of this model with consistent performance when tested using datasets acquired from a variety of image-acquisition environments.

Sequential Connection of Mutually Exclusive Catalytic Reactions by a Method Controlling the Presence of an MOF Catalyst: One-Pot Oxidation of Alcohols to Carboxylic Acids.

A functionalized metal-organic framework (MOF) catalyst applied to the sequential one-pot oxidation of alcohols to carboxylic acids controls the presence of a heterogeneous catalyst. The conversion of alcohols to aldehydes was acquired through aerobic oxidation using a well-known amino-oxy radical-functionalized MOF. In the same flask, a simple filtration of the radical MOF with mild heating of the solution completely altered the reaction media, providing radical scavenger-free conditions suitable for the autoxidation of the aldehydes formed in the first step to carboxylic acids. The mutually exclusive radical-catalyzed aerobic oxidation (the first step with MOF) and radical-inhibited autoxidation (the second step without MOF) are sequentially achieved in a one-pot manner. Overall, we demonstrate a powerful and efficient method for the sequential oxidation of alcohols to carboxylic acids by employing a readily functionalizable heterogeneous MOF. In addition, our MOF in-and-out method can be utilized in an environmentally friendly way for the oxidation of alcohols to carboxylic acids of industrial and economic value with broad functional group tolerance, including 2,5-furandicarboxylic acid and 1,4-benzenedicarboxylic acid, with good yield and reusability. Furthermore, MOF-TEMPO, as an antioxidative stabilizer, prevents the undesired oxidation of aldehydes, and the perfect "recoverability" of such a reactive MOF requires a re-evaluation of the advantages of MOFs from heterogeneity in catalytic and related applications.

Multi-slice representational learning of convolutional neural network for Alzheimer's disease classification using positron emission tomography.

BACKGROUND: Alzheimer's Disease (AD) is a degenerative brain disorder that often occurs in people over 65 years old. As advanced AD is difficult to manage, accurate diagnosis of the disorder is critical. Previous studies have revealed effective deep learning methods of classification. However, deep learning methods require a large number of image datasets. Moreover, medical images are affected by various environmental factors. In the current study, we propose a deep learning-based method for diagnosis of Alzheimer's disease (AD) that is less sensitive to different datasets for external validation, based upon F-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT). RESULTS: The accuracy, sensitivity, and specificity of our proposed network were 86.09%, 80.00%, and 92.96% (respectively) using our dataset, and 91.02%, 87.93%, and 93.57% (respectively) using the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. We observed that our model classified AD and normal cognitive (NC) cases based on the posterior cingulate cortex (PCC), where pathological changes occur in AD. The performance of the GAP layer was considered statistically significant compared to the fully connected layer in both datasets for accuracy, sensitivity, and specificity (p < 0.01). In addition, performance comparison between the ADNI dataset and our dataset showed no statistically significant differences in accuracy, sensitivity, and specificity (p > 0.05). CONCLUSIONS: The proposed model demonstrated the effectiveness of AD classification using the GAP layer. Our model learned the AD features from PCC in both the ADNI and Severance datasets, which can be seen in the heatmap. Furthermore, we showed that there were no significant differences in performance using statistical analysis.

A new species of Thoracophelia (Annelida, Opheliidae) from the Yellow Sea of South Korea.

Background: Thoracophelia Ehlers, 1897 is a genus of Opheliidae characterised by the body divided into three distinct regions, modified parapodia in chaetiger 10 and a ventral groove restricted to the posterior half of the body. To date, 18 species have been described in the genus. Amongst them, six species have been recorded in northeast Asia. New information: A new species, Thoracopheliafoliformis sp. nov., was discovered in the intertidal zone of the Yellow Sea, South Korea. This is the first Thoracophelia species report from the Yellow Sea. This new species is closely related to T.dillonensis (Hartman, 1938) from California and T.ezoensis Okuda, 1936 from Japan in having pectinate branchiae. However, the new species can be distinguished from the two species by the unique combination of the following characteristics: 15 pairs of wrinkled pectinate branchiae with 12-15 filaments at best development and a foliaceous mid-ventral plate in the pygidium instead of one or two thick ventral cirri. Detailed descriptions and illustrations of T.foliformis sp. nov. are provided. Sequences of the mitochondrial cytochrome c oxidase subunit I (COI), nuclear 18S ribosomal DNA (rDNA) and 28S rDNA of the new species were determined and analysed.

The preventive effect of Gastrodia elata Blume extract on vancomycin-induced acute kidney injury in rats.

BACKGROUND: Gastrodia elata Blume (GEB), a traditional medicinal herb, has been reported to have pharmacological effect including protection against liver, neuron and kidney toxicity. However, explanation of its underlying mechanisms remains a great challenge. This study investigated the protective effects of GEB extract on vancomycin (VAN)-induced nephrotoxicity in rats and underlying mechanisms with emphasis on the anti-oxidative stress, anti-inflammation and anti-apoptosis. The male Sprague-Dawley rats were randomly divided three groups: control (CON) group, VAN group and GEB group with duration of 14 days. RESULTS: The kidney weight and the serum levels of blood urea nitrogen and creatinine in the GEB group were lower than the VAN group. Histological analysis using hematoxylin & eosin and periodic acid Schiff staining revealed pathological changes of the VAN group. Immunohistochemical analysis revealed that the expression levels of N-acetyl-D-glucosaminidase, myeloperoxidase and tumor necrosis factor-alpha in the GEB group were decreased when compared with the VAN group. The number of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive cells, phosphohistone and malondialdehyde levels were lower in the GEB group than VAN group. The levels of total glutathione in the GEB group were higher than the VAN group. CONCLUSIONS: The findings of this study suggested that GEB extract prevents VAN-induced renal tissue damage through anti-oxidation, anti-inflammation and anti-apoptosis.

A Case of Esophageal MALT Lymphoma Mimicking a Subepithelial Tumor.

Mucosa-associated lymphoid tissue (MALT) lymphoma, also known as extranodal marginal zone lymphoma, is a low-grade B-cell lymphoma that can develop in the mucosal layer of various organs, including the gastrointestinal tract, salivary glands, lungs, and skin. The most common site is the gastrointestinal tract, particularly the stomach. On the other hand, primary esophageal lymphomas are extremely rare. MALT lymphomas can undergo histological transformation into more aggressive B-cell lymphomas, such as diffuse large B-cell lymphoma, resulting in a poor prognosis. This paper reports a rare case of primary esophageal MALT lymphoma mimicking a subepithelial tumor located in the lower esophagus that was treated successfully with radiotherapy. MALT lymphoma should be included in a differential diagnosis when subepithelial tumors are found in the esophagus, particularly if endoscopic ultrasonography reveals the tumor to be located in the deep mucosal and submucosal layers. Following the precise diagnosis, accurate staging and appropriate treatment are crucial. Regular follow-up is necessary to assess the possibility of recurrence or transformation to high-grade lymphoma.

Thin, Uniform, and Highly Packed Multifunctional Structural Carbon Fiber Composite Battery Lamina Informed by Solid Polymer Electrolyte Cure Kinetics.

Multifunctional structural batteries promise advancements in structural energy storage technologies by seamlessly integrating load-bearing and energy-storage functions within a single material, reducing weight, and enhancing safety. Yet, commercialization faces challenges in materials processing, assembly, and design optimization. Here, we report a systematic approach to develop a carbon fiber (CF)-based structural battery impregnated with epoxy-based solid polymer electrolyte (SPE) via robust vacuum-assisted compression molding (VACM). Informed by cure kinetics, SPE processing enhances the multifunctional performance with no fillers or additives. The thin flexible CF-based laminae impregnated under high pressure achieved a substantial enhancement of ∼160% in the fiber volume fraction (FVF) as although thin and strip-shaped, the fibers were optimally packed with low void. A CF/SPE-based battery was fabricated, with a hybrid layered ionic liquid (IL)/ carbonate electrolyte (CE) showing enhanced safety and multifunctional performance. Enhanced by thin, uniform, and stiff CF-based composites, this study propels the development of advanced multifunctional structures, thereby expediting sustainable commercialization.

The complete mitochondrial genome of the mauve stinger jellyfish Pelagia noctiluca Forskål, 1775 (Cnidaria, Scyphozoa, Semaeostomeae) with phylogenetic analysis.

This study determined the complete mitochondrial genome of the jellyfish Pelagia noctiluca (Scyphozoa, Semaeostomeae) for the first time. The genome was a linear molecule of 16,390 bp in length and 59.3% AT. It comprised of 13 typical protein-coding genes (cox1-3, nd1-6, nd4L, atp6, atp8, and cytB), two ribosomal RNAs (16S and 12S rRNA), and two tRNAs (trnM and trnW). In addition, we detected two additional open reading frames (polB and ORF314) at one end of the genome. The gene-coding structures were identical to those of other scyphozoans. Based on a molecular phylogeny constructed using 13 protein-coding genes, P. noctiluca has the closest genetic relationship with the genus Chrysaora (Semaeostomeae).

Symbiotic relationship between filamentous algae (Halomicronema sp.) and extracellular polymeric substance-producing algae (Chlamydomonas sp.) through biomimetic simulation of natural algal mats.

To lower the cost of biomass harvesting, the growth of natural biofilm is considered to be an optimal alternative to microalgae aggregation. This study investigated algal mats that naturally agglomerate into a lump and float on water surfaces. Halomicronema sp., a filamentous cyanobacterium with high cell aggregation and adhesion to substrates, and Chlamydomonas sp., which grows rapidly and produces high extracellular polymeric substances (EPS) in certain environments, are the main microalgae that make up selected mats through next-generation sequencing analysis. These two species play a major role in the formation of solid mats, and showed a symbiotic relationship as the medium and nutritional source, particularly owing to the large amount of EPS formed by the reaction between EPS and calcium ions through zeta potential and Fourier-transform infrared spectroscopy analysis. This led to the formation of an ecological biomimetic algal mat (BAM) that mimics the natural algal mat system, and this is a way to reduce costs in the biomass production process as there is no separate treatment process for harvesting.

Levosimendan inhibits disulfide tau oligomerization and ameliorates tau pathology in TauP301L-BiFC mice.

Tau oligomers play critical roles in tau pathology and are responsible for neuronal cell death and transmitting the disease in the brain. Accordingly, preventing tau oligomerization has become an important therapeutic strategy to treat tauopathies, including Alzheimer's disease. However, progress has been slow because detecting tau oligomers in the cellular context is difficult. Working toward tau-targeted drug discovery, our group has developed a tau-BiFC platform to monitor and quantify tau oligomerization. By using the tau-BiFC platform, we screened libraries with FDA-approved and passed phase I drugs and identified levosimendan as a potent anti-tau agent that inhibits tau oligomerization. 14C-isotope labeling of levosimendan revealed that levosimendan covalently bound to tau cysteines, directly inhibiting disulfide-linked tau oligomerization. In addition, levosimendan disassembles tau oligomers into monomers, rescuing neurons from aggregation states. In comparison, the well-known anti-tau agents methylene blue and LMTM failed to protect neurons from tau-mediated toxicity, generating high-molecular-weight tau oligomers. Levosimendan displayed robust potency against tau oligomerization and rescued cognitive declines induced by tauopathy in the TauP301L-BiFC mouse model. Our data present the potential of levosimendan as a disease-modifying drug for tauopathies.

BET protein inhibition promotes non-myeloid cell mediated neuroprotection after rodent spinal cord contusion.

Spinal cord injuries (SCI) often lead to multiple neurological deficits as a result from the initial trauma and also the secondary damage that follows. Despite abundant preclinical data proposing anti-inflammatory therapies to minimize secondary injury and improve functional recovery, the field still lacks an effective neuroprotective treatment. Epigenetic proteins, such as bromodomain and extraterminal domain (BET) proteins, are emerging as new targets to regulate inflammation. More importantly, pharmacological inhibition of BET proteins suppresses pro-inflammatory gene transcription after SCI. In this study, we tested the therapeutic potential of inhibiting BET proteins after SCI with clinically relevant compounds, and investigated the role of the BET protein BRD4 in macrophages during progression of SCI pathology. Systemic inhibition of BET proteins with I-BET762 significantly reduced lesion size 8 weeks after a contusion injury in rats. However, we observed no histological or locomotor improvements after SCI when we deleted Brd4 in macrophages through the use of myeloid-specific Brd4 knockout mice or after macrophage-targeted pharmacological BET inhibition. Taken together, our data indicate that systemic I-BET762 treatment is neuroprotective, and the histopathological improvement observed is likely to be a result of effects on non-macrophage targets. Expanding our understanding on the role of BET proteins after SCI is necessary to identify novel therapeutic targets that can effectively promote repair after SCI.