bluuebunny/crossref_metadata_2025 huggingface dataset:
A case of rectal metastasis of prostate cancer mimicking extramural growth-type rectal tumor
Authors: Hike Shutaro , Endo Satoshi , Ota Masayuki , Ohira Gaku , Maruyama Michihiro , Imanishi Shunsuke , Maruyama Tetsuro , Tochigi Toru , Amagai Hiroyuki , Shiraishi Tadashi , Hirata Atsushi , Mamiya Hisashi , Iwata Moe , Kakimoto Ayano , Matsubara Hisahiro
Published: May 2024

Rectal metastases of prostate cancer are rare and may be difficult to diagnose. In this report, we describe a case in which an extramural growth-type rectal tumor was resected and pathologically diagnosed as prostate cancer metastasis. A 70-year-old man on hormone therapy for prostate cancer with seminal vesicle invasion and pelvic lymph node metastasis was referred to our department after an imaging scan showed an extramural growth-type rectal tumor. Endoscopic ultrasound-guided fine needle aspiration was considered for diagnosis, but the patient preferred an early resection without the exam, so surgery was performed. Histopathological examination revealed that the lesion was in the adventitia of the rectum and metastasis of prostate cancer. Metastatic lesions of prostate cancer are not indicated for resection. A detailed preoperative study with the possibility of prostate cancer metastasis in mind is necessary because it is relevant to choosing the treatment strategy.
Right ventricular outflow tract obstruction by cardiac hemangioma in asymptomatic patient
Authors: Kaewboonlert Naritsaret , Chunharas Piyapat , Pluthikarmpae Naree , Poontananggul Jiraphon , Wongthep Akharawat , Pongsuwan Natthipong , Lerssuttipon Udomsak
Published: May 2024

Ventricular hemangiomas are rare benign tumors, pose diagnostic and therapeutic complexities. We report a case of a 52-year-old female with essential hypertension who developed a systolic ejection murmur during a hypertension clinic visit. The echocardiogram revealed a hyperechoic mass obstructing the right ventricular outflow tract, causing enlargement of the right atrium and ventricle, with a reduction in the right ventricular ejection fraction. Due to the risk of death, the patient underwent an emergency surgical resection along with tricuspid valve replacement. Postoperative recovery was uneventful, and subsequent cardiac magnetic resonance imaging showed an improvement in ejection fraction without residual tumor. This case highlights the diagnosis and therapeutic complexities of ventricular hemangiomas. With this report, we aim to provide a comprehensive review of ventricular hemangiomas and to enhance understanding of this condition for improved patient care.
Intracranial meningeal melanocytoma: a case report and literature review
Authors: Chintapalli Renuka
Published: May 2024

Primary intracranial melanocytoma is an uncommon benign pigmented tumor arising from leptomeningeal melanocytes. Neuroimaging characteristics of central nervous system melanocytoma are distinct from similarly presenting intracranial neoplasms and can aid in diagnosis prior to histopathological examination. In rare cases, there may be more than one lesion present. We report a case of a 19-year-old woman presenting with progressively worsening headaches, nausea, emesis, and generalized weakness of 2 months. Imaging revealed tumors in the parietal and ipsilateral medial temporal lobe. The patient underwent gross total resection of the parietal lesion which histopathological assessment revealed to be primary intracranial meningeal melanocytoma. This case highlights the utility of specific imaging criteria such as diffusely increased T1 signal without enhancement in the initial diagnostic evaluation of intracranial melanocytoma. We also describe the clinical characteristics, management strategy, and histopathological features of a rare case of a patient with multiple primary intracranial melanocytoma lesions.
Sex Differences in Screening Positive for Post-Traumatic Stress Disorder After Combat Injury
Authors: MacGregor Andrew J , Dougherty Amber L , Crouch Daniel J , Dye Judy L
Published: May 2024

Introduction

U.S. military women were at risk of combat exposure and injury from asymmetric warfare during the conflicts in Iraq and Afghanistan. Previous research has yielded mixed results when examining sex differences in PTSD following operational deployment. To date, no study has explored sex differences in PTSD after combat injury.

Materials and Methods

This retrospective study included U.S. military service men and women who experienced a combat injury in Iraq or Afghanistan (March 2003 to March 2013) and completed a Post-Deployment Health Assessment (PDHA) within 1 year of injury. The PDHA is administered at the end of deployment and includes the 4-item Primary Care PTSD Screen. The prevalence of screening positive for PTSD was evaluated by sex using a chi-square test. Multivariable logistic regression was used to assess the association between sex and PTSD while adjusting for covariates.

Results

The study sample included 16,215 injured military personnel (666 women and 15,549 men). The average time between injury and PDHA was 132 days (SD = 91.0). Overall, women had a higher prevalence of screening positive for PTSD than men (48.3% vs. 40.9%, P < .001). In multivariable regression, women had higher odds than men of screening positive for PTSD (odds ratio, 1.34; 95% confidence interval, 1.14-1.57). Psychiatric history was the strongest predictor of screening positive for PTSD regardless of sex (odds ratio, 1.59; 95% confidence interval, 1.45-1.74).

Conclusions

In this novel study of military service members, women were more likely to screen positive for PTSD than men after combat injury. Strategies to mitigate PTSD, enhance resiliency, and incorporate psychological care into injury rehabilitation programs for women may be needed for future U.S. military conflicts where they will play a larger role in combat operations.
Obesity and Overweight: First Comprehensive Overview in the French Armed Forces
Authors: Mannaioni Livia , Jay Thierry , Goudard Yvain , Aoun Olivier , Pauleau Ghislain , Montois Anne , de La Villéon Bruno
Published: May 2024

Introduction

The global rise in obesity is well-established, with significant health implications. This study aims to comprehensively assess overweight and obesity prevalence within the French Armed Forces.

Materials and Methods

Using data from the Unique Medical-Military Software (UMMS) in 2018, a cross-sectional study was conducted on active French Military personnel aged 18 and above, who underwent periodic medical examinations (PME) in 2017. Body Mass Index (BMI) served as the main criterion for overweight and obesity classification. A representative sample was obtained through random sampling.

Results

The sample included 17,082 individuals, revealing an average age of 33.5 years, with 36.1% classified as overweight and 9.6% as obese. The mean BMI of women was significantly lower than that of men (23.9 vs 25.3 kg/m2—P < .001). Results indicated that 22.4% of women vs 38.5% of men were overweight (P < .001). For obesity, the difference was not significant (8.8% of women vs 9.8% of men—P = .138). BMI increased with age, and non-commissioned officers (NCOs) showed the highest prevalence of obesity. Gendarmes exhibited the highest BMI and overweight rates (50.1%) among military branches.

Conclusion

While obesity is less prevalent in the French Armed Forces compared to the general population, the study emphasizes the equivalent prevalence of overweight. We confirm here that the global epidemic of obesity and overweight affects all armed forces. France seems less affected than other Western armies. Targeting specific groups, such as NCOs and the national gendarmerie, is crucial for prevention.
A genetically encoded fluorescent heme sensor detects free heme in plants
Authors: Wen Bingxiao , Grimm Bernhard
Published: May 2024

Heme is produced in plants via a plastid-localized metabolic pathway and is subsequently distributed to all cellular compartments. In addition to covalently and noncovalently bound heme, a comparatively small amount of free heme that is not associated with protein is available for incorporation into heme-dependent proteins in all subcellular compartments and for regulatory purposes. This “labile” fraction may also be toxic. To date, the distribution of the free heme pool in plant cells remains poorly understood. Several fluorescence-based methods for the quantification of intracellular free heme have been described. For this study, we used the previously described genetically encoded heme sensor 1 (HS1) to measure the relative amounts of heme in different plant subcellular compartments. In a proof of concept, we manipulated heme content using a range of biochemical and genetic approaches and verified the utility of HS1 in different cellular compartments of Arabidopsis (Arabidopsis thaliana) and tobacco (Nicotiana tabacum and Nicotiana benthamiana) plants transformed either transiently or stably with HS1 and HS1(M7A), a variant with lower affinity for heme. This approach makes it possible to trace the distribution and dynamics of free heme and provides relevant information about its mobilization. The application of these heme sensors will create opportunities to explore and validate the importance of free heme in plant cells and to identify mutants that alter the subcellular allocation of free heme.
The Racial Limits of Disruption: How Race and Tactics Influence Social Movement Organization Testimony before Congress, 1960–1995
Authors: Maher Thomas V , Seguin Charles , Zhang Yongjun
Published: May 2024

Social movement theory holds that disrupting social and political processes is among the most effective tools social movement organizations (SMOs) use to motivate recognition for themselves and their constituents. Yet, recent research suggests that the political reception of disruption is not racially neutral. Black SMOs face a dilemma in that, although disruption is a powerful tool for change, the public often perceives nonviolent Black disruptive protest as violent. We investigate this bind by analyzing how nondisruptive protest, nonviolent disruption, or violence helps or hinders both Black and non-Black SMOs to gain state “acceptance” as legitimate spokes-organizations for their issues. We combine data on newspaper-reported protest events with data covering 41,545 SMO Congressional testimonies from 1462 SMOs from 35 movement families. In panel regressions, we find that Congress is generally more accepting of nondisruptive protest but that nondisruptive protest is only roughly one-tenth as effective for Black SMOs compared with non-Black SMOs. Furthermore, whereas non-Black SMOs are significantly more likely to testify after using nonviolent disruption, Black SMOs using nonviolent disruption are significantly less likely to testify before Congress. Regardless of race, violence was associated with fewer congressional testimonies. Collectively, these findings suggest that Black SMOs face a tactical bind: Black SMOs can use nondisruptive tactics that are resource-intensive and slow, or they can use nonviolent disruption that gets media attention but hinders congressional acceptance. These findings contribute to a growing literature on how racial inequality and prejudice impact the outcomes of social movements.
Longitudinal Trajectories of Antiretroviral Treatment Adherence and Associations With Durable Viral Suppression Among Adolescents Living With HIV in South Africa
Authors: Zhou Siyanai , Cluver Lucie , Knight Lucia , Edun Olanrewaju , Sherman Gayle , Toska Elona
Published: May 2024

Background:

Compared with other age groups, adolescents living with HIV (ALHIV) are estimated to have lower levels of adherence to antiretroviral treatment. Despite this, we lack evidence on adolescents' adherence patterns over time to inform the customization of intervention strategies.

Setting:

Eastern Cape province, South Africa.

Methods:

We analyzed data from a cohort of ALHIV (N = 1046, aged 10–19 years at baseline) recruited from 53 public health facilities. The cohort comprised 3 waves of data collected between 2014 and 2018 and routine viral load data from the National Institute for Communicable Disease data warehouse (2014–2019). Durable viral suppression was defined as having suppressed viral load (<1000 copies/mL) at ≥2 consecutive study waves. Group-based multitrajectory model was used to identify adherence trajectories using 5 indicators of self-reported adherence. Logistic regression modeling evaluated the associations between adherence trajectories and durable viral suppression.

Results:

Overall, 933 ALHIV (89.2%) completed all 3 study waves (55.1% female, mean age: 13.6 years at baseline). Four adherence trajectories were identified, namely, “consistent adherence” (49.8%), “low start and increasing” (20.8%), “gradually decreasing” (23.5%), and “low and decreasing” (5.9%). Adolescents experiencing inconsistent adherence trajectories were more likely to be older, live in rural areas, and have sexually acquired HIV. Compared with the consistent adherence trajectory, the odds of durable viral suppression were lower among adolescents in the low start and increasing (adjusted odds ratio [aOR]: 0.62, 95% CI: 0.41 to 0.95), gradually decreasing (aOR: 0.40, 95% CI: 0.27 to 0.59), and the low and decreasing adherence (aOR: 0.25, 95% CI: 0.10 to 0.62) trajectories.

Conclusions:

Adherence to antiretroviral treatment remains a challenge among ALHIV in South Africa. Identifying adolescents at risk of nonadherence, based on their adherence trajectories may inform the tailoring of adolescent-friendly support strategies.
The laboratory investigation, management, and infection prevention and control of Candida auris: a narrative review to inform the 2024 national guidance update in England
Authors: Jones Christopher R. , Neill Claire , Borman Andrew M. , Budd Emma L. , Cummins Martina , Fry Carole , Guy Rebecca L. , Jeffery Katie , Johnson Elizabeth M. , Manuel Rohini , Mirfenderesky Mariyam , Moore Ginny , Patel Bharat , Schelenz Silke , Staniforth Karren , Taori Surabhi K. , Brown Colin S.
Published: May 2024

The emergent fungal pathogen Candida auris is increasingly recognised as an important cause of healthcare-associated infections globally. It is highly transmissible, adaptable, and persistent, resulting in an organism with significant outbreak potential that risks devastating consequences. Progress in the ability to identify C. auris in clinical specimens is encouraging, but laboratory diagnostic capacity and surveillance systems are lacking in many countries. Intrinsic resistance to commonly used antifungals, combined with the ability to rapidly acquire resistance to therapy, substantially restricts treatment options and novel agents are desperately needed. Despite this, outbreaks can be interrupted, and mortality avoided or minimised, through the application of rigorous infection prevention and control measures with an increasing evidence base. This review provides an update on epidemiology, the impact of the COVID-19 pandemic, risk factors, identification and typing, resistance profiles, treatment, detection of colonisation, and infection prevention and control measures for C. auris. This review has informed a planned 2024 update to the United Kingdom Health Security Agency (UKHSA) guidance on the laboratory investigation, management, and infection prevention and control of Candida auris. A multidisciplinary response is needed to control C. auris transmission in a healthcare setting and should emphasise outbreak preparedness and response, rapid contact tracing and isolation or cohorting of patients and staff, strict hand hygiene and other infection prevention and control measures, dedicated or single-use equipment, appropriate disinfection, and effective communication concerning patient transfers and discharge.
Whitening effects of fermented Trigonotis radicans var. sericea with Lactobacillus brevis in α-MSH-stimulated B16F10 melanoma cells
Authors: Jeong Da-Eun , Kim Byung-Oh , Cho Young-Je
Published: May 2024

This study was designed to compare the whitening effects of 60% ethanol extracts of Trigonotis radicans var. sericea (TR) and Lactobacillus brevis-fermented T. radicans var. sericea (FTR). Measurement of cytotoxicity in B16-F10 melanoma cells to confirm the whitening effect, FTR showed higher cell viability than TR. FTR showed inhibitory activity on melanin contents similar to the normal group at concentrations of 50 and 100 μg/mL. MITF expression was used to confirm the effect on melanogenesis-related protein expression. TR and FTR showed significant concentration-dependent decrease, and FTR showed lower expressions than the normal group at concentrations of 25, 50, and 100 μg/mL. Additionally, the mRNA expression of melanogenesis-related genes (MC1R, Rab27a, TGF-β1 and Myo5a) were measured by RT-qPCR to confirm the whitening effect. In MC1R expression at a concentration of 100 μg/mL in FTR showed effective inhibitory activities, and in TGF-β1 expression, TR and FTR both showed effective activities compared to normal groups even at low concentrations. Results of myo5a and Rab27a, a similar pattern was shown, and FTR showed effective inhibitory activities at a concentration of 100 μg/mL. As a result, FTR had higher whitening effects through bioconversion and is expected to be a good material for whitening functional cosmetics.
StarFunc: fusing template-based and deep learning approaches for accurate protein function prediction
Authors: Zhang Chengxin , Liu Quancheng , Freddolino Lydia
Published: May 2024

Deep learning has significantly advanced the development of high-performance methods for protein function prediction. Nonetheless, even for state-of-the-art deep learning approaches, template information remains an indispensable component in most cases. While many function prediction methods use templates identified through sequence homology or protein-protein interactions, very few methods detect templates through structural similarity, even though protein structures are the basis of their functions. Here, we describe our development of StarFunc, a composite approach that integrates state-of-the-art deep learning models seamlessly with template information from sequence homology, protein-protein interaction partners, proteins with similar structures, and protein domain families. Large-scale benchmarking and blind testing in the 5thCritical Assessment of Function Annotation (CAFA5) consistently demonstrate StarFunc’s advantage when compared to both state-of-the-art deep learning methods and conventional template-based predictors.
Building Brains for Robots: A Hands-On Approach to Learning Neuroscience in the Classroom
Authors: Kannan Raha , Gendreau Maribel , Hatch Alex , Free Sydney K. , Muriungi Kithinji , Garje Yash A. , DeBoer Jennifer , Gage Gregory J. , Harris Christopher A.
Published: May 2024

As the relevance of neuroscience in education grows, effective methods for teaching this complex subject in high school classrooms remain elusive. Integrating classroom experiments with brain-based robots offers a promising solution. This paper presents a structured curriculum designed around the use of camera-equipped mobile robots which enables students to construct and explore artificial neural networks. Through this hands-on approach, students engage directly with core concepts in neuroscience, learning to model spiking neural networks, decision-making processes in the basal ganglia, and principles of learning and memory. The curriculum not only makes challenging neuroscience concepts accessible and engaging but also demonstrates significant improvements in students’ understanding and self-efficacy. By detailing the curriculum’s development, implementation, and educational outcomes, this study outlines a scalable model for incorporating advanced scientific topics into secondary education, paving the way for a deeper student understanding of both theoretical neuroscience and its practical applications.
The balance between antiviral and antibacterial responses duringM. tuberculosisinfection is regulated by the ubiquitin ligase CBL
Authors: Truong Tina , Martin Kelsey , Salemi Michelle , Ray Abigail , Phinney Brett S. , Penn Bennett H.
Published: May 2024

As a first line of host defense, macrophages must be able to effectively sense and respond to diverse types of pathogens, and while a particular type of immune response may be beneficial in some circumstances, it can be detrimental in others. Upon infecting a macrophage,M. tuberculosis(Mtb) induces proinflammatory cytokines that activate antibacterial responses. Surprisingly,Mtbalso triggers antiviral responses that actually hinder the ability of macrophages to controlMtbinfection. The ubiquitin ligase CBL suppresses these antiviral responses and shifts macrophages toward a more antibacterial state duringMtbinfection, however, the mechanisms by which CBL regulates immune signaling are unknown. We found that CBL controls responses to multiple stimuli and broadly suppresses the expression of antiviral effector genes. We then used mass-spectrometry to investigate potential CBL substrates and identified over 46,000 ubiquitylated peptides inMtb-infected macrophages, as well as roughly 400 peptides with CBL-dependent ubiquitylation. We then performed genetic interaction analysis of CBL and its putative substrates, and identified the Fas associated factor 2 (FAF2) adapter protein as a key signaling molecule protein downstream of CBL. Together, these analyses identify thousands of new ubiquitin-mediated signaling events during the innate immune response and reveal an important new regulatory hub in this response.
Heat stress and recovery induce transcriptomic changes in lactogenic bovine mammary epithelial (MAC-T) cells
Authors: Yu Xingtan , Harman Rebecca M. , Danev Nikola , Li Guangsheng , Fang Yifei , Van de Walle Gerlinde R. , Duan Jingyue Ellie
Published: May 2024

Heat stress (HS) in cattle significantly challenges the dairy industry by reducing milk production. However, the molecular mechanism behind mammary gland responses to HS and recovery remains poorly understood. This study aimed to determine the transcriptomic changes in lactogenic bovine mammary epithelial (MAC-T) cells after HS and post-HS recovery. Six culture conditions were analyzed: MAC-T cells cultured in basal medium, cells in lactogenic medium to induce differentiation, differentiated cells at standard temperature (37℃) or HS (42℃) for 1 hour. HS cells were collected after incubation at 37℃ for either 2 or 6 hours to examine the extent of recovery.

A total of 1,668 differentially expressed genes (DEGs) were identified. Differentiated cells expressed genes associated with milk lipid synthesis, indicating lactogenic potential. HS suppressed genes involved in cellular differentiation and activated heat shock protein genes. Several transcription factors were identified as potential regulators of HS response. During recovery, chaperon-mediated protein folding genes remained elevated. Apoptosis regulation genes were induced at 2 hours, and cellular homeostasis regulation genes were enriched at 6 hours. Overall, these findings provide a foundation for the molecular mechanisms involved in HS and recovery in cattle.
Intrinsic skeletal muscle function and contraction-stimulated glucose uptake do not vary by time-of-day in mice
Authors: Fitzgerald Liam S. , Bremner Shannon N. , Ward Samuel R. , Cho Yoshitake , Schenk Simon
Published: May 2024

A growing body of data suggests that skeletal muscle contractile function and glucose metabolism vary by time-of-day, with chronobiological effects on intrinsic skeletal muscle properties being proposed as the underlying mediator. However, no studies have directly investigated intrinsic contractile function or glucose metabolism in skeletal muscle over a 24 h circadian cycle. To address this, we assessed intrinsic contractile function and endurance, as well as contraction-stimulated glucose uptake, in isolated extensor digitorum longus and soleus from female mice at four times-of-day (Zeitgeber Times 1, 7, 13, 19). Significantly, while both muscles demonstrated circadian-related changes in gene expression, intrinsic contractile function, endurance, and contraction-stimulated glucose uptake were not different between the four time points. Overall, these results demonstrate that time-of-day variation in exercise performance and the glycemia-reducing benefits of exercise are not due to chronobiological effects on intrinsic muscle function or contraction-stimulated glucose uptake.

Impact statement

Ex vivotesting demonstrates that there is no time-of-day variation in the intrinsic contractile properties of skeletal muscle (including no effect on force production or endurance) or contraction-stimulated glucose uptake.
Unveiling the Secrets of Extracellular Vesicles in Urban Water Systems: Understanding the Link Between Human and Environmental Health
Authors: Liu Fei , Li Yi , Piao Yunxian , Wang Yong , Liang Zaiyao , Lee Luke P.
Published: May 2024

It is crucial to gain valuable insights into the ecological health of rivers to inform management decisions and protect sustainable living conditions. Understanding biological information is vital to gaining insight into river ecosystem biodiversity, but reliable methods are challenging. Here, We investigate the potential impact of extracellular vesicles (EVs) in urban water systems on human and environmental health to promote urban sustainability. We used EXODUS to detect EVs and perform metaproteomic analysis on samples from an urban water system that contained human feces, wastewater, bacteria, plants, arthropods, and soil. We analyzed EVs collected from urban and green areas, observing taxonomic variations and discovering bacterial contributions to their protein content. According to our research, the abundance and expression levels of proteins in EVs can indicate how human activities affect microbial communities in rivers, potentially impacting public health. Our study offers a fresh perspective on the interconnectedness of urban sustainability, public health, and river ecosystem biodiversity.
Annelid comparative genomics and the evolution of massive lineage-specific genome rearrangement in bilaterians
Authors: Lewin Thomas D. , Liao Isabel Jiah-Yih , Luo Yi-Jyun
Published: May 2024

The organization of genomes into chromosomes is critical for processes such as genetic recombination, environmental adaptation, and speciation. All animals with bilateral symmetry inherited a genome structure from their last common ancestor that has been highly conserved in some taxa but seemingly unconstrained in others. However, the evolutionary forces driving these differences and the processes by which they emerge have remained largely uncharacterized. Here we analyze genome organization across the phylum Annelida using 23 chromosome-level annelid genomes. We find that while most annelids have maintained the conserved bilaterian genome structure, a group containing leeches and earthworms possesses completely scrambled genomes. We develop a rearrangement index to quantify the extent of genome structure evolution and show leeches and earthworms to have the most highly rearranged genomes of any currently sampled bilaterian. We further show that bilaterian genomes can be classified into two distinct categories—high and low rearrangement—largely influenced by the presence or absence, respectively, of chromosome fission events. Our findings demonstrate that animal genome structure can be highly variable within a phylum and reveal that genome rearrangement can occur both in a gradual, stepwise fashion or as rapid, all-encompassing changes over short evolutionary timescales.
Molecular Mechanism of Huanglian Jiedu Decoction in Treatment of Alzheimer’s Disease based on Network Pharmacology
Authors: Ye Qiuyan , Li Xue , Gao Wei , Zhang Yutong , Zhang Miao-miao , Zheng Liping , Li Honglin
Published: May 2024

Purpose

The aim of this study was to investigate the pharmacological mechanism of Huanglian Jiedu Decoction (HLJDD) in treating Alzheimer’s disease through network pharmacology. HLJDD is a classic Chinese medicine prescription that is recommended in the Chinese Alzheimer’s disease diagnosis and treatment guidelines. However, the mechanism of HLJDD treatment for Alzheimer’s disease (AD) remains unclear because of its complicated components.

Methods

The related ingredients and targets of HLJDD in treating AD were screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis platform (TCMSP), TTD, OMIM, GeneCards, and DrugBank. The data of the protein-protein interaction (PPI) network was constructed using STRING. The Metascape database was adopted for Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. AutoDockTools was used for molecular docking verification.

Results

In the treatment of AD, HLJDD demonstrated strong efficacy with its core active components including were quercetin, β-sitosterol, stigmasterol, targeting key proteins such as AKT1, TNF, and IL6. Molecular docking tests confirmed the significant binding affinity between these components and the aforementioned targets. The biological pathway of HLJDD in treating AD primarily involves the modulation of IL-17, TNF, and other inflammatory cytokines to regulate their impact on nerve functions.

Conclusions

HLJDD may treat AD by inhibiting neuroinflammation through a comprehensive, multi-component, multi-target, and multi-pathway method.
Mature adipocytes inhibit differentiation of myogenic cells but stimulate proliferation of fibro-adipogenic precursors derived from trout musclein vitro
Authors: Goffette Valentine , Sabin Nathalie , Bugeon Jerôme , Jagot Sabrina , Hue Isabelle , Gabillard Jean-Charles
Published: May 2024

Interactions between tissues and cell types, mediated by cytokines or direct cell-cell exchanges, regulate growth. To determine whether mature adipocytes influence thein vitrodevelopment of trout mononucleated muscle cells, we developed an indirect coculture system, and showed that adipocytes (5×106cells/well) derived from perivisceral adipose tissue increased the proliferation (BrdU+) of the mononucleated muscle cells (26%versus39%; P<0.001) while inhibiting myogenic differentiation (myosin+) (25%versus15%; P<0.001). Similar effects were obtained with subcutaneous adipose tissue-derived adipocytes, although requiring more adipocytes (3×107cells/wellversus5×106cells/well). Conditioned media recapitulated these effects, stimulating proliferation (31%versus39%; p<0.001) and inhibiting myogenic differentiation (32%versus23%; p<0.001). Adipocytes began to reduce differentiation after 24 hours, whereas proliferation stimulation was observed after 48 hours. While adipocytes did not changepax7+andmyoD1/2+percentages, they reducedmyogenin+cells showing inhibition from early differentiation stage. Finally, adipocytes increased BrdU+cells in thePdgfrα+population but not in themyoD+one. Collectively, our results demonstrate that trout adipocytes promote fibro-adipocyte precursor proliferation while inhibiting myogenic cells differentiationin vitro, suggesting the key role of adipose tissue in regulating fish muscle growth.
Autofluorescence lifetime flow cytometry with time‐correlated single photon counting
Authors: Samimi Kayvan , Pasachhe Ojaswi , Guzman Emmanuel Contreras , Riendeau Jeremiah , Gillette Amani A. , Pham Dan L. , Wiech Kasia J. , Moore Darcie L. , Skala Melissa C.
Published: May 2024

Autofluorescence lifetime imaging microscopy (FLIM) is sensitive to metabolic changes in single cells based on changes in the protein-binding activities of the metabolic co-enzymes NAD(P)H. However, FLIM typically relies on time-correlated single-photon counting (TCSPC) detection electronics on laser-scanning microscopes, which are expensive, low-throughput, and require substantial post-processing time for cell segmentation and analysis. Here, we present a fluorescence lifetime-sensitive flow cytometer that offers the same TCSPC temporal resolution in a flow geometry, with low-cost single-photon excitation sources, a throughput of tens of cells per second, and real-time single-cell analysis. The system uses a 375nm picosecond-pulsed diode laser operating at 50MHz, alkali photomultiplier tubes, an FPGA-based time tagger, and can provide real-time phasor-based classification (i.e., gating) of flowing cells. A CMOS camera produces simultaneous brightfield images using far-red illumination. A second PMT provides two-color analysis. Cells are injected into the microfluidic channel using a syringe pump at 2-5 mm/s with nearly 5ms integration time per cell, resulting in a light dose of 2.65 J/cm2that is well below damage thresholds (25 J/cm2at 375 nm). Our results show that cells remain viable after measurement, and the system is sensitive to autofluorescence lifetime changes in Jurkat T cells with metabolic perturbation (sodium cyanide), quiescent vs. activated (CD3/CD28/CD2) primary human T cells, and quiescent vs. activated primary adult mouse neural stem cells, consistent with prior studies using multiphoton FLIM. This TCSPC-based autofluorescence lifetime flow cytometer provides a valuable label-free method for real-time analysis of single-cell function and metabolism with higher throughput than laser-scanning microscopy systems.
A plant-specific clade of serine/arginine-rich proteins regulates RNA splicing homeostasis and thermotolerance in tomato
Authors: Rosenkranz Remus RE , Vraggalas Stavros , Keller Mario , Sankaranarayanan Srimeenakshi , McNicoll François , Löchli Karin , Bublak Daniela , Benhamed Moussa , Crespi Martin , Berberich Thomas , Bazakos Christos , Feldbrügge Michael , Schleiff Enrico , Müller-McNicoll Michaela , Zarnack Kathi , Fragkostefanakis Sotirios
Published: May 2024

High temperatures cause heat stress (HS), which has negative effects on plant growth and development and affects many cellular processes including pre-mRNA splicing. In tomato plants the splicing profile of many of genes is altered under HS, including that ofHSFA2, a central transcriptional regulator of thermotolerance. To identify the core splicing regulators of HS-sensitive alternative splicing, we usedHSFA2as bait and identified two plant-specific members of the serine/arginine-rich family of splicing factors, namely RS2Z35 and RS2Z36, that inhibitHSFA2intron splicing. Single and double CRISPR mutants of these proteins show dysregulated splicing of many genes and exhibit lower basal and acquired thermotolerance. Individual-nucleotide resolution UV cross-linking and immunoprecipitation (iCLIP) of tomato leaves revealed that the majority of HS-sensitive alternatively spliced RNAs are bound by RS2Z35 and RS2Z36 and this interaction occurs at purine-rich RNA motifs. Phenotypic and transcriptome analyses revealed that RS2Z35 and RS2Z36 are important players in the stress response and thermotolerance in plants that mitigate the negative effects of HS on RNA splicing homeostasis.
Physiological role and mechanisms of action for a long noncoding haplotype region
Authors: Xue Hong , Mishra Manoj K. , Liu Yong , Liu Pengyuan , Grzybowski Michael , Pandey Rajan , Usa Kristie , Vanden Avond Mark A. , Bala Niharika , Alli Abdel A. , Cowley Allen W. , Qiu Qiongzi , Greene Andrew S. , Rao Sridhar , O’Meara Caitlin C. , Geurts Aron M. , Liang Mingyu
Published: May 2024

Most common sequence variants associated with human traits are in noncoding regions of the genome, form haplotypes with other noncoding variants, and exhibit small effect sizes in the general population. Determining the physiological roles and mechanisms of action for these noncoding variants, particularly large haplotypes containing multiple variants, is both critical and challenging. To address this challenge, we developed an approach that integrates physiological studies in genetically engineered and phenotypically permissive animal models, precise editing of large haplotypes in human induced pluripotent stem cells (hiPSCs), and targeted chromatin conformation analysis. We applied this approach to examine the blood pressure associated rs1173771 locus, which includes a haplotype containing 11 single nucleotide polymorphisms (SNPs) spanning 17.4 kbp. Deleting the orthologous noncoding region in the genome of the Dahl salt-sensitive rat attenuated the salt-induced increase in systolic blood pressure by nearly 10 mmHg. This attenuation of hypertension appeared to be mediated by upregulation of the adjacent geneNpr3(natriuretic peptide receptor 3) in arteries, enhancing vasodilation. The blood pressure-elevating and -lowering haplotypes were precisely reconstituted in hiPSCs using an efficient, two-step genome editing technique. The blood pressure-elevating haplotype decreased NPR3 expression in endothelial cells and vascular smooth muscle cells derived from the edited, isogenic hiPSCs. The influence of the haplotype was partially recapitulated by the sentinel SNP rs1173771. Additionally, the blood pressure-elevating haplotype showed significantly greater chromatin interactions with theNPR3promoter region. This study illustrates the feasibility of ascertaining the physiological roles and mechanisms of action for large noncoding haplotypes. Our efficient, integrated, and targeted approach can be applied to investigate other noncoding variants.
Catechol acetylglucose: A newly identified benzoxazinoid-regulated defensive metabolite in maize
Authors: Richter Annett , Schroeder Allen F. , Marcon Caroline , Hochholdinger Frank , Jander Georg , Negin Boaz
Published: May 2024

An enormous diversity of specialized metabolites is produced in the plant kingdom, with each individual plant synthesizing thousands of these compounds. Previous research showed that benzoxazinoids, the most abundant class of specialized metabolites in maize, also function as signaling molecules by regulating the production callose as a defense response. In this study, we identified catechol acetylglucose (CAG) as a benzoxazinoid-regulated metabolite that is produced from salicylic acid via catechol and catechol-glucoside. Genome wide association studies of CAG abundance identified a gene encoding a predicted acetyltransferase. Knockout of this gene resulted in maize plants that lack CAG and over-accumulate catechol glucoside. Upon tissue disruption, maize plants accumulate catechol, which inhibitsSpodoptera frugiperda(fall armyworm) growth. Analysis of caterpillar frass showed thatS. frugiperdadetoxifies catechol by glycosylation, and the efficiency of catechol glycosylation was correlated withS. frugiperdagrowth on a catechol-containing diet. Thus, the success ofS. frugiperdaas an agricultural pest may depend partly on its ability to detoxify catechol, which is produced as a defensive metabolite by maize plants.
Expanding the Triangle of U: The genome assembly ofHirschfeldia incanaprovides insights into chromosomal evolution, phylogenomics and high photosynthesis-related traits
Authors: Hoang Nam V. , Walden Nora , Caracciolo Ludovico , Luoni Sofia Bengoa , Retta Moges , Li Run , Wolters Felicia C. , Woldu Tina , Becker Frank F. M. , Verbaarschot Patrick , Harbinson Jeremy , Driever Steven M. , Struik Paul C. , Amerongen Herbert van , de Ridder Dick , Aarts Mark G.M. , Schranz M. Eric
Published: May 2024

The Brassiceae tribe encompasses many economically important crops and exhibits high intraspecific and interspecific phenotypic variation. After a shared whole-genome triplication (WGT) event (Br-α, ∼15.9 million years ago), different lineages and species underwent differential chromosomal rearrangements (diploidization) leading to diverse patterns of gene retention and loss (fractionation). Lineage diversification and genomic changes contributed to an array of divergence in morphology, biochemistry, and physiology underlying photosynthesis-related traits. The C3speciesHirschfeldia incanais studied as it displays high photosynthetic rates under high-light conditions. We present an improved chromosome-level genome assembly forH. incana(Nijmegen, v2.0) using nanopore and chromosome conformation capture (Hi-C) technologies, with 409Mb in size and an N50 of 52Mb (a 10× improvement over the previously published scaffold-level v1.0 assembly). The updated assembly and annotation allowed to investigate the WGT history ofH. incanain a comparative phylogenomic framework from the Brassiceae ancestral genomic blocks and related diploidized crops.Hirschfeldia incana(x=7) shares extensive genome collinearity withRaphanus sativus(x=9). These two species share some commonalities withBrassica rapaandB. oleracea(A genome, x=10 and C genome, x=9, respectively) and other similarities withB. nigra(B genome, x=8). Phylogenetic analysis revealed thatH. incanaandR. sativusform a monophyletic clade in between theBrassicaA/C and B genomes. We postulate thatH. incanaandR. sativusgenomes are results of reciprocal hybridization combinations of theBrassicaA/C and B genome types. Our results might explain the discrepancy observed in published studies regarding phylogenetic placement ofH. incanaandR. sativusin relation to the “Triangle of U” species. Expression analysis of WGT retained gene copies revealed sub-genome expression divergence, likely due to neo- or sub-functionalization. Finally, we highlighted genes associated with physio-biochemical-anatomical adaptive changes observed inH. incanawhich likely facilitate its high-photosynthesis traits under high light.
Impact of flagellated and elongated morphological phenotypes on the focusing behaviours of biological cells in inertial microfluidic devices
Authors: Howell Jessie , Hall Nicole , Omwenga Sulochana , Hammarton Tansy C. , Jimenez Melanie
Published: May 2024

Inertial microfluidics has demonstrated tremendous potential to impact biological - and notably medical - fields, by offering a highly versatile, portable and cost-effective approach to cell focusing and sorting. While the range of applications of inertial devices spans medical diagnostics, bioprocessing or water engineering to mention a few, translation is still impeded by the lack of clear understanding of cell interactions in such devices. This often leads to bespoke designs that take years of development and characterisation for one targeted application, and limited tools for informed optimisation. A more fundamental knowledge of inertial behaviours is key to future translational works and impact, by enabling a deeper understanding of inertial forces in biological systems. Towards this goal, this paper focuses on high-throughput morphological phenotyping of the single-celled, flagellated parasiteLeishmania mexicanato better understand how variations in cell body length, width and flagellated status impact the focusing patterns of highly non-spherical cells in curved inertial devices. Some of the key findings in this study include i) not all organelles, such as flagella, will alter focusing if the body shape is conserved, ii) the impact of cell shape is specific to a channel design and slight changes in e.g., cell confinement can completely change focusing patterns, iii) elongated prolate-like cells align in different orientations depending on their lateral position with a curved channel and iv) despite variabilities observed in focusing patterns for elongated versus rounder cell phenotypes, large morphological variations can be completely overcome at high Reynolds numbers so that all phenotypes tightly focus at a single position (here towards the channel outer wall). This last finding, in particular, may open new avenues for highly efficient cell enrichment processes, such as for the detection of pathogens in water.
Reduced beta-hydroxybutyrate disposal after ketogenic diet feeding in mice
Authors: Cousineau Cody M , Snyder Detrick , Redd JeAnna R. , Turner Sophia , Carr Treyton , Bridges Dave
Published: May 2024

The ketogenic diet (KD) has garnered considerable attention due to its potential benefits in weight loss, health improvement, and performance enhancement. However, the phenotypic responses to KD vary widely between individuals. Skeletal muscle is a major contributor to ketone body (KB) catabolism, however, the regulation of ketolysis is not well understood. In this study, we evaluated how mTORC1 activation and a ketogenic diet modify ketone body disposal in muscle Tsc1 knockout (KO) mice, inbred A/J mice, and Diversity Outbred (DO) mice. Muscle Tsc1 KO mice demonstrated enhanced ketone body clearance. Contrary to expectations, KD feeding in A/J mice did not improve KB disposal, and in most strains disposal was reduced. Transcriptional analysis revealed reduced expression of important ketolytic genes in KD-fed A/J mice, suggesting impaired KB catabolism. Diversity Outbred (DO) mice displayed variable responses to KD, with most mice showing worsened KB disposal. Exploratory analysis on these data suggest potential correlations between KB disposal and cholesterol levels as well as weight gain on a KD. Our findings suggest that ketone body disposal may be regulated by both nutritional and genetic factors and these relationships may help explain interindividual variability in responses to ketogenic diets.
Protein CoAlation on TXNRD2 regulates mitochondrial thioredoxin system to protect against ferroptosis
Authors: Lin Chao-Chieh , Lin Yi-Tzu , Chen Ssu-Yu , Setayeshpour Yasaman , Chen Yubin , Dunn Denise E , Soderblom Erik J , Zhang Guo-Fang , Filonenko Valeriy , Jeong Suh Young , Floyd Scott , Hayflick Susan J , Gout Ivan , Chi Jen-Tsan
Published: May 2024

The Cystine-xCT transporter-Glutathione (GSH)-GPX4 axis is the canonical pathway to protect against ferroptosis. While not required for ferroptosis-inducing compounds (FINs) targeting GPX4, FINs targeting the xCT transporter require mitochondria and its lipid peroxidation to trigger ferroptosis. However, the mechanism underlying the difference between these FINs is still unknown. Given that cysteine is also required for coenzyme A (CoA) biosynthesis, here we show that CoA supplementation specifically prevents ferroptosis induced by xCT inhibitors but not GPX4 inhibitors. We find that, auranofin, a thioredoxin reductase inhibitor, abolishes the protective effect of CoA. We also find that CoA availability determines the enzymatic activity of thioredoxin reductase, but not thioredoxin. Importantly, the mitochondrial thioredoxin system, but not the cytosolic thioredoxin system, determines CoA-mediated ferroptosis inhibition. Our data show that the CoA regulates thein vitroenzymatic activity of mitochondrial thioredoxin reductase (TXNRD2) by covalently modifying the thiol group of cysteine (CoAlation) on Cys-483. Replacing Cys-483 with alanine on TXNRD2 abolishes itsin vitroenzymatic activity and ability to protect cells from ferroptosis. Targeting xCT to limit cysteine import and, therefore, CoA biosynthesis reduced CoAlation on TXNRD2, an effect that was rescued by CoA supplementation. Furthermore, the fibroblasts from patients with disrupted CoA metabolism demonstrate increased mitochondrial lipid peroxidation. In organotypic brain slice cultures, inhibition of CoA biosynthesis leads to an oxidized thioredoxin system, mitochondrial lipid peroxidation, and loss in cell viability, which were all rescued by ferrostatin-1. These findings identify CoA-mediated post-translation modification to regulate the thioredoxin system as an alternative ferroptosis protection pathway with potential clinical relevance for patients with disrupted CoA metabolism.