Miracle-dz/UniFAR-FTUs huggingface dataset:
From water to land: Evolution of photoreceptor circuits for vision in air

When vertebrates first conquered the land, they encountered a visual world that was radically distinct from that of their aquatic ancestors. Fish exploit the strong wavelength-dependent interactions of light with water by differentially feeding the signals from up to 5 spectral photoreceptor types into distinct behavioural programmes. However, above the water the same spectral rules do not apply, and this called for an update to visual circuit strategies. Early tetrapods soon evolved the double cone, a still poorly understood pair of new photoreceptors that brought the “ancestral terrestrial” complement from 5 to 7. Subsequent nonmammalian lineages differentially adapted this highly parallelised retinal input strategy for their diverse visual ecologies. By contrast, mammals shed most ancestral photoreceptors and converged on an input strategy that is exceptionally general. In eutherian mammals including in humans, parallelisation emerges gradually as the visual signal traverses the layers of the retina and into the brain.
Serum proteomics reveals APOE dependent and independent protein signatures in Alzheimer’s disease

The current demand for early intervention, prevention, and treatment of late onset Alzheimer’s disease (LOAD) warrants deeper understanding of the underlying molecular processes which could contribute to biomarker and drug target discovery. Utilizing high-throughput proteomic measurements in serum from a prospective population-based cohort of older adults (n = 5,294), we identified 303 unique proteins associated with incident LOAD (median follow-up 12.8 years). Over 40% of these proteins were associated with LOAD independently of APOE-ε4 carrier status. These proteins were implicated in neuronal processes and overlapped with protein signatures of LOAD in brain and cerebrospinal fluid. We found 17 proteins which LOAD-association was strongly dependent on APOE-ε4 carrier status. Most of them showed consistent associations with LOAD in cerebrospinal fluid and a third had brain-specific gene expression. Remarkably, four proteins in this group (TBCA, ARL2, S100A13 and IRF6) were downregulated by APOE-ε4 yet upregulated as a consequence of LOAD as determined in a bi-directional Mendelian randomization analysis, reflecting a potential response to the disease onset. Accordingly, the direct association of these proteins to LOAD was reversed upon APOE-ε4 genotype adjustment, a finding which we replicate in an external cohort (n = 719). Our findings provide an insight into the dysregulated pathways that may lead to the development and early detection of LOAD, including those both independent and dependent on APOE-ε4. Importantly, many of the LOAD-associated proteins we find in the circulation have been found to be expressed - and have a direct link with AD - in brain tissue. Thus, the proteins identified here, and their upstream modulating pathways, provide a new source of circulating biomarker and therapeutic target candidates for LOAD.
Clinical, Pathological and Virological Outcomes of Tissue-Homogenate-Derived and Cell-Adapted Strains of Porcine Epidemic Diarrhea Virus (PEDV) in a Neonatal Pig Model

Porcine epidemic diarrhea virus (PEDV) is characterized by diarrhea, vomiting, dehydration, and high mortality rates in neonatal piglets. Two distinct genogroups, S-INDEL (G1a, G1b) and non-S INDEL (G2a, G2b, and G2c), circulate worldwide and are characterized by varying degrees of virulence. Here, we compared the early pathogenesis of a PEDV S-INDEL strain obtained from intestine homogenate (CALAF-HOMOG) or adapted to cell culture by 22 passages (CALAF-ADAP) and a virulent non-S INDEL strain (PEDV-USA) in newborn piglets. After orogastric inoculation of PEDV strains, body weight, temperature and clinical signs were monitored for 48 hpi. Pathological studies were performed at 48 hpi and RNA extracts from jejunal content (at 48 hpi) and rectal swabs (at 0 and 48 hpi) were tested for the presence of PEDV RNA as well as sequenced and compared to the inoculum. Piglets inoculated with PEDV-USA and CALAF-HOMOG isolates showed more severe weight loss, diarrhea, villi fusion and atrophy compared to CALAF-ADAP inoculated piglets. The viral load of rectal swabs was higher in the PEDV-USA inoculated group, followed by CALAF-HOMOG and CALAF-ADAP isolates. Similarly, viral RNA load in jejunal content was comparable among PEDV-USA and CALAF-HOMOG inoculated piglets and higher than that of CALAF-ADAP ones. The comparison of three full PEDV sequences of the inocula with the corresponding ones of pigs after 48 hpi yielded a nucleotide identity >99.9%. This study highlights variations in virulence among S-INDEL and non-S INDEL strains and between S-INDEL isolates obtained from homogenate and cell culture.
Maintenance Chemotherapy in Patients with Platinum-Sensitive Relapsed Epithelial Ovarian Cancer after Second-Line Chemotherapy

(1) Background: Our aim was to evaluate the efficacy and adverse effects of maintenance chemotherapy in platinum-sensitive recurrent epithelial ovarian cancer after second-line chemotherapy. (2) Methods: A total of 72 patients from a single institute who had been diagnosed with platinum-sensitive recurrent ovarian cancer and had experienced either complete or partial response after six cycles of second-line chemotherapy were divided into a standard group (n = 31) with six cycles or a maintenance group (n = 41) with more than six cycles. We then compared patient characteristics and survival outcomes between these two groups. (3) Results: In all patients, after primary management for the first recurrence, the maintenance group showed worse survival outcomes. Patients who had not undergone either surgery or radiotherapy were divided into complete response and partial response groups after six cycles of chemotherapy. In patients with partial response, maintenance chemotherapy led to a significant improvement in PFS (median, 3.6 vs. 6.7 months, p = 0.007), but no significant change in in OS. The median cycle number of maintenance chemotherapy was four. (4) Conclusions: Maintenance chemotherapy may still play an important role in patients with platinum-sensitive recurrent ovarian cancer, particularly in selected patient groups.
The Need for Novel Asexual Blood-Stage Malaria Vaccine Candidates for Plasmodium falciparum

Extensive control efforts have significantly reduced malaria cases and deaths over the past two decades, but in recent years, coupled with the COVID-19 pandemic, success has stalled. The WHO has urged the implementation of a number of interventions, including vaccines. The modestly effective RTS,S/AS01 pre-erythrocytic vaccine has been recommended by the WHO for use in sub-Saharan Africa against Plasmodium falciparum in children residing in moderate to high malaria transmission regions. A second pre-erythrocytic vaccine, R21/Matrix-M, was also recommended by the WHO on 3 October 2023. However, the paucity and limitations of pre-erythrocytic vaccines highlight the need for asexual blood-stage malaria vaccines that prevent disease caused by blood-stage parasites. Few asexual blood-stage vaccine candidates have reached phase 2 clinical development, and the challenges in terms of their efficacy include antigen polymorphisms and low immunogenicity in humans. This review summarizes the history and progress of asexual blood-stage malaria vaccine development, highlighting the need for novel candidate vaccine antigens/molecules.
Dosimetric Comparison Study of Proton Therapy Using Line Scanning versus Passive Scattering and Volumetric Modulated Arc Therapy for Localized Prostate Cancer

Simple Summary The currently documented outcomes of proton therapy for patients with localized prostate cancer are based on passive scattering (PS). In this study, we compared the dose distribution of the line scanning (LS) method, one of the pencil beam scanning (PBS) techniques, with that of PS and volumetric modulated arc therapy (VMAT) in 30 patients. The results showed that LS could significantly reduce the wide range of rectal and bladder doses compared to the PS and VMAT while upholding the requisite target dose. The results suggest that proton therapy for prostate cancer with the PBS method may have the potential to reduce toxicities further while preserving therapeutic efficacies. Abstract Background: The proton irradiation modality has transitioned from passive scattering (PS) to pencil beam scanning. Nevertheless, the documented outcomes predominantly rely on PS. Methods: Thirty patients diagnosed with prostate cancer were selected to assess treatment planning across line scanning (LS), PS, and volumetric modulated arc therapy (VMAT). Dose constraints encompassed clinical target volume (CTV) D98 ≥ 73.0 Gy (RBE), rectal wall V65 < 17% and V40 < 35%, and bladder wall V65 < 25% and V40 < 50%. The CTV, rectal wall, and bladder wall dose volumes were calculated and evaluated using the Freidman test. Results: The LS technique adhered to all dose limitations. For the rectal and bladder walls, 10 (33.3%) and 21 (70.0%) patients in the PS method and 5 (16.7%) and 1 (3.3%) patients in VMAT, respectively, failed to meet the stipulated requirements. The wide ranges of the rectal and bladder wall volumes (V10-70) were lower with LS than with PS and VMAT. LS outperformed VMAT across all dose–volume rectal and bladder wall indices. Conclusion: The LS method demonstrated a reduction in rectal and bladder doses relative to PS and VMAT, thereby suggesting the potential for mitigating toxicities.
RNA-Seq Analysis Revealed circRNAs and Genes Associated with Abdominal Fat Deposition in Ducks

Simple Summary Fat deposition affects the quality of meat ducks and their feed conversion efficiency. In this study, we analyzed the correlations between abdominal fat and other growth traits, and performed RNA-seq of the abdominal fat tissue of ducks with high and low abdominal fat ratio, exploring the key regulatory genes and circRNAs related to abdominal fat deposition. We investigated the functions of both source and target genes of these circRNAs and constructed a competing endogenous RNA network. The findings revealed several circRNAs and their relationships with microRNAs and messenger RNAs that are pivotal in duck abdominal fat deposition. The results of this study establish a groundwork for understanding the molecular mechanisms that regulate abdominal fat deposition in ducks, offering a theoretical reference for the selective breeding of high-quality meat-producing ducks. Abstract Fat deposition is an important factor affecting meat quality and feed conversion efficiency in meat ducks. This study aims to identify key circRNAs and genes affecting abdominal fat deposition. The correlations between abdominal fat and other growth performances were analyzed in 304 F2 generation of Cherry Valley duck Runzhou Crested White ducks, and an RNA-seq analysis of abdominal fat tissues from ducks with high and low rates of abdominal fat was performed. Growth performance results showed that Abdominal fat ratio and Intramuscular fat were significantly higher in the high rates of abdominal fat (HF)group than in the low rates of abdominal fat (LF) group for ducks. RNA-seq analysis of abdominal fat tissue unveiled 85 upregulated and 72 downregulated circRNAs among the differentially expressed ones. Notably, 74 circRNAs displayed more than four-fold differential expression, constituting 47.13% of the differentially expressed genes. Functional enrichment analysis of the differentially expressed circRNA source and target genes indicated that 17 circRNAs might partake in regulating duck abdominal fat production by influencing pathways like PPAR signaling, lipid droplets, and triglyceride metabolism. Lastly, multiple circRNA-microRNA-messenger RNA interaction networks were constructed. The results of this study establish the groundwork for understanding the molecular mechanisms that regulate abdominal fat deposition in ducks, offering a theoretical reference for the selective breeding of high-quality meat-producing ducks.
The Development of a Measuring System for Intraoral SpO2

Blood oxygen saturation (SpO2) is an essential indicator of a patient’s general condition. However, conventional measurement methods have some issues such as time delay and interference by ambient light. Improved measurement methods must be developed, and there are no reports on intraoral measurements of SpO2 using wearable devices. Therefore, we aimed to establish an intraoral SpO2 measurement method for the first time. Twelve healthy adults participated in this study. The following steps were taken: (1) to identify the optimal measurement location, mid-perfusion index (PI) values were measured at six places on the mucosa of the maxilla, (2) to validate the optimal measurement pressure, PI values were obtained at different pressures, and (3) using the proposed mouthpiece device, SpO2 values in the oral cavity and on the finger were analyzed during breath-holding. The highest PI values were observed in the palatal gingiva of the maxillary canine teeth, with high PI values at pressures ranging from 0.3 to 0.8 N. In addition, changes in SpO2 were detected approximately 7 s faster in the oral cavity than those on the finger, which is attributed to their proximity to the heart. This study demonstrates the advantage of the oral cavity for acquiring biological information using a novel device.
Vernal distribution and turnover of dimethylsulfide (DMS) in the surface water of the Yellow Sea

The spatial and interannual variations of dimethylsulfide (DMS) and its precursors, dissolved and particulate dimethylsulfoniopropionate (DMSP), were discussed on the basis of field observations in the surface waters of the Yellow Sea during spring 2007. Maxima of dimethylated sulfur compounds and low chlorophyll a concentrations were found in the central southern Yellow Sea, whereas low concentrations of DMS and DMSP were detected at the boundary between the northern and southern parts of the Yellow Sea. This frontal region is influenced by active water currents, air–sea interface exchanges, and biological turnover. The horizontal variations in DMS production and consumption rates showed a decreasing tendency from the coastal to offshore areas mainly due to the complicated biological features. DMS positively correlated with dissolved CH4 and CO2 but negatively correlated with nutrients (nitrite and phosphate). Particulate DMSP concentrations and DMS production rates positively correlated with dinoflagellate abundances but negatively correlated with diatom cell densities. DMS and DMSP concentrations, as well as DMS production and consumption rates, exhibited approximately 2.0-2.8 fold increases from 2005 to 2012. This finding was likely caused by shifts in the phytoplankton communities from diatoms to dinoflagellates and the increases in abundances of zooplankton and bacteria. Average sea-to-air DMS fluxes were estimated to be 8.12 ± 1.24 µmol·(m−2·d−1), and DMS microbial consumption was approximately 1.68 times faster than the DMS sea–air exchange. These findings imply that biological consumption, relative to ventilation, is a predominant mechanism in DMS removal from the surface water. This article is protected by copyright. All rights reserved.
Exploring the Hemostatic Effects of Platelet Lysate-Derived Vesicles: Insights from Mouse Models

Platelet transfusion has various challenges, and platelet-derived extracellular vesicles have been reported to have more significant procoagulant activity than platelets themselves. Furthermore, platelet products derived from platelet-rich plasma and platelet lysates (PLs) have gained attention for their physiological activity and potential role as drug delivery vehicles owing to the properties of their membranes. We aimed to investigate the characteristics of the fractions isolated through ultracentrifugation from mouse-washed PLs and assess the potential clinical applications of these fractions as a therapeutic approach for bleeding conditions. We prepared PLs from C57BL/6 mouse-washed platelets and isolated three different fractions (20K-vesicles, 100K-vesicles, and PLwo-vesicles) using ultracentrifugation. There was a notable difference in particle size distribution between 20K-vesicles and 100K-vesicles, particularly in terms of the most frequent diameter. The 20K-vesicles exhibited procoagulant activity with concentration dependence, whereas PLwo-vesicles exhibited anticoagulant activity. PLwo-vesicles did not exhibit thrombin generation capacity, and the addition of PLwo-vesicles to Microparticle Free Plasma extended the time to initiate thrombin generation by 20K-vesicles and decreased the peak thrombin value. In a tail-snip bleeding assay, pre-administration of 20K-vesicles significantly shortened bleeding time. PL-derived 20K-vesicles exhibited highly potent procoagulant activity, making them potential alternatives to platelet transfusion.
Needle-Free Jet Injection of Poly-(Lactic Acid) for Atrophic Acne Scars: Literature Review and Report of Clinical Cases

Acne scars, particularly atrophic ones, present a persistent challenge in cosmetic medicine and surgery, requiring extended and multifaceted treatment approaches. Poly-(lactic acid) injectable fillers show promise in managing atrophic acne scars by stimulating collagen synthesis. However, the utilization of needle-free injectors for delivering poly-(lactic acid) into scars remains an area requiring further exploration. In this article, a summary of the latest advancements in needle-free jet injectors is provided, specifically highlighting the variations in jet-producing mechanisms. This summary emphasizes the differences in how these mechanisms operate, offering insights into the evolving technology behind needle-free injection systems. The literature review revealed documented cases focusing on treating atrophic acne scars using intralesional poly-(lactic acid) injections. The results of these clinical studies could be supported by separate in vitro and animal studies, elucidating the feasible pathways through which this treatment operates. However, there is limited information on the use of needle-free jet injectors for the intradermal delivery of poly-(lactic acid). Clinical cases of atrophic acne scar treatment are presented to explore this novel treatment concept, the needle-free delivery of poly-(lactic acid) using a jet pressure-based injector. The treatment demonstrated efficacy with minimal adverse effects, suggesting its potential for scar treatment. The clinical efficacy was supported by histological evidence obtained from cadaver skin, demonstrating an even distribution of injected particles in all layers of the dermis. In conclusion, we suggest that novel needle-free injectors offer advantages in precision and reduce patient discomfort, contributing to scar improvement and skin rejuvenation. Further comprehensive studies are warranted to substantiate these findings and ascertain the efficacy of this approach in scar treatment on a larger scale.
Molecular Mechanisms and Regulatory Pathways Underlying Drought Stress Response in Rice

Rice is a staple food for 350 million people globally. Its yield thus affects global food security. Drought is a serious environmental factor affecting rice growth. Alleviating the inhibition of drought stress is thus an urgent challenge that should be solved to enhance rice growth and yield. This review details the effects of drought on rice morphology, physiology, biochemistry, and the genes associated with drought stress response, their biological functions, and molecular regulatory pathways. The review further highlights the main future research directions to collectively provide theoretical support and reference for improving drought stress adaptation mechanisms and breeding new drought-resistant rice varieties.
Site-Specific Transient Receptor Potential Channel Mechanisms and Their Characteristics for Targeted Chronic Itch Treatment

Chronic itch is a debilitating condition with limited treatment options, severely affecting quality of life. The identification of pruriceptors has sparked a growing interest in the therapeutic potential of TRP channels in the context of itch. In this regard, we provided a comprehensive overview of the site-specific expression of TRP channels and their associated functions in response to a range of pruritogens. Although several potent antipruritic compounds that target specific TRP channels have been developed and have demonstrated efficacy in various chronic itch conditions through experimental means, a more thorough understanding of the potential for adverse effects or interactions with other TRP channels or GPCRs is necessary to develop novel and selective therapeutics that target TRP channels for treating chronic itch. This review focuses on the mechanism of itch associated with TRP channels at specific sites, from the skin to the sensory neuron, with the aim of suggesting specific therapeutic targets for treating this condition.
Differential Gene Expression in Human Fibroblasts Simultaneously Exposed to Ionizing Radiation and Simulated Microgravity

During future space missions, astronauts will be exposed to cosmic radiation and microgravity (μG), which are known to be health risk factors. To examine the differentially expressed genes (DEG) and their prevalent biological processes and pathways as a response to these two risk factors simultaneously, 1BR-hTERT human fibroblast cells were cultured under 1 gravity (1G) or simulated μG for 48 h in total and collected at 0 (sham irradiated), 3 or 24 h after 1 Gy of X-ray or Carbon-ion (C-ion) irradiation. A three-dimensional clinostat was used for the simulation of μG and the simultaneous radiation exposure of the samples. The RNA-seq method was used to produce lists of differentially expressed genes between different environmental conditions. Over-representation analyses were performed and the enriched biological pathways and targeting transcription factors were identified. Comparing sham-irradiated cells under simulated μG and 1G conditions, terms related to response to oxygen levels and muscle contraction were identified. After irradiation with X-rays or C-ions under 1G, identified DEGs were found to be involved in DNA damage repair, signal transduction by p53 class mediator, cell cycle arrest and apoptosis pathways. The same enriched pathways emerged when cells were irradiated under simulated μG condition. Nevertheless, the combined effect attenuated the transcriptional response to irradiation which may pose a subtle risk in space flights.