Conectar
by Navdeep Kaur, Marcus V. Merfa, Alexandra K. Kahn, Rodrigo P. P. Almeida, Leonardo De La Fuente
Xylella fastidiosa (Xf) is an insect-transmitted, xylem-limited bacterial plant pathogen that infects hundreds of plant species. This pathogen causes bacterial leaf scorch in southern highbush blueberry (Vaccinium corymbosum interspecific hybrids) in the southeastern United States, a disease that has not yet been reported elsewhere. Previously, a comparative genomic analysis of Xf and ancestral host species identified evolutionary events of gene gain and loss related to host range specificity. Here, by using a similar workflow, we identified two loci that are significantly found in blueberry-infecting strains. Locus_1088 included a hypothetical protein and a small part of the N-terminus of an orphan RelE toxin, while Locus_2741 was annotated as a hypothetical protein. Using a protocol based on natural competence, mutants were generated in three Xf subsp. multiplex strains from blueberry. Less biofilm, more planktonic growth, and increased twitching motility as compared to its wild-type (WT) were observed for the strain LA-Y3C_1088 mutant. In blueberry virulence assays, the LA-Y3C_1088 mutant caused significantly more severe symptoms than LA-Y3C_WT, whereas no significant differences were observed for other mutated strains. Interestingly the mutation of Locus_1088 additionally disrupted a toxin (part of a toxin-antitoxin system) that is likely responsible for the phenotypic changes observed. However, because the two independent mutants were not generated, we could not determine whether the phenotype resulted from disruption of hypothetical protein or the toxin. Additionally, since the coffee-isolated but never tested in blueberry Xf subsp. fastidiosa strain CFBP8073 was found to encode the two blueberry-associated loci studied here, its virulence was assessed in blueberry. This strain caused severe symptoms comparable to the control strain AlmaEm3 from blueberry. Due to the complexity of understanding host specificity in Xf, any advance in identifying genetic markers for host specificity in this devastating pathogen could greatly improve management of Xf worldwide.by Meirong Shan, Qian Guo, Ruofei Li, Ni Li, Yanhua Fu, Huanyu Qi, Ge Zhang, Qian Wang, Xingli Xu, Jinchuan Lai
Hypertension is one of the main causes of cardiovascular diseases worldwide, affecting over one billion people. Although aliskiren offers a valuable option for inhibiting the renin-angiotensin system, its safety profile in the real world remains insufficiently explored, especially for rare or under-recognized adverse events (AEs), which have not been fully clarified. Therefore, leveraging large-scale post-marketing surveillance data is crucial for identifying rare AEs and guiding safer clinical practice. This study aims to elucidate pharmacovigilance signals associated with aliskiren (an antihypertensive drug) by systematically analyzing the characteristics of adverse events (AEs) from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database and WHO-VigiAccess database, which provides a reliable scientific basis for clinical practice and regulatory decision-making. We conducted a retrospective quantitative analysis of aliskiren-related AE reports from the aforementioned two databases, employing the Proportional Reporting Ratio (PRR), Reporting Odds Ratio (ROR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS) algorithms for signal detection. The results indicate that there were 5,596 and 5,549 aliskiren-related reports in the FAERS and WHO-VigiAccess databases, respectively. The median duration of these AEs during the observation period was 62 days, with an interquartile range (IQR) of 7–282 days. In both databases, signals for aliskiren were distributed across 28 System Organ Classes (SOCs), among which investigations, cardiac disorders, renal and urinary disorders, vascular disorders, and metabolism and nutrition disorders exhibited significant signals based on specific criteria applied across the four algorithms. A total of 607 preferred terms (PTs) with significant disproportionality signals were detected using the four algorithms, including potential AEs not previously well-documented, such as palpitations, myalgia, proteinuria, muscular weakness, pulmonary edema, and pollakiuria. This study not only confirms the known adverse reactions of aliskiren but also uncovers new potential risks, highlighting the importance of strengthening drug safety monitoring to enhance therapeutic efficacy and reduce the risk of adverse reactions. It provides valuable safety insights for physicians considering the use of aliskiren in the management of primary hypertension.by Mingming Pan, Yanhua Shen, Jiayu Wu, Chaonan Liu, Meihong Zhu, Zhengyu Zhou
This study aimed to investigate the therapeutic effects of ELASEM®Flex and ELASEM®ProFlex, two eggshell membrane (EM) products, on sodium iodoacetate (MIA)-induced osteoarthritis (OA) in rats. An OA model was established by a single intra-articular injection of MIA into the knee joint. After modeling, rats were administered diclofenac sodium, ELASEM®Flex, and ELASEM®ProFlex by gavage daily for 4 consecutive weeks. During the experiment, food intake, water intake, body weight, and plantar mechanical pain threshold (MPT) of rats were measured weekly. Serum levels of TNF-α, COX-2, IL-1β, and CTX-II were assessed at weeks 2 and 4. After 4 weeks, knee joints were harvested for histopathological examination (HE staining and Safranin-O fast green staining). Results indicated that knee joints of OA rats showed significant swelling, which was alleviated to varying degrees in all treatment groups. Both ELASEM®Flex and ELASEM®ProFlex significantly increased the MPT (P ®Flex and ELASEM®ProFlex can exert preventive and reparative effects on knee OA in rats by alleviating arthritis pain, inhibiting inflammatory factor expression, reducing type II collagen degradation, and promoting chondrocyte proliferation.by Hang Sun, Haozhi Xu, Junying Li, Xiaoman Xie, Junmei Zhang, Hongjie Dong, Huanhuan Xie, Qi Wang, Guihua Zhao, Kun Yin, Jingyu Yang, Jianwei Zhou, Ruili Wu, Chao Xu
Gastric cancer (GC) is one of the most common and lethal cancers globally. methyltransferase-like 3 (METTL3)-mediated N6-methyladenosine (m6A) RNA methylation plays a crucial role in tumor initiation and progression by regulating RNA function. STM2457, a highly efficient METTL3 inhibitor, can inhibit METTL3 activity and may serve as a potential therapeutic strategy in cancers. However, the role of STM2457 for GC cells is still unknown. In this study, we analyzed the expression profile data of GC in TCGA and GEO databases, and further explored the expression involvement of METTL3 in GC cell line, investigated the therapeutic effect of STM2457 targeted inhibition of METTL3 in GC both in vitro and in vivo experiments. The results indicated that STM2457 could suppress GC cell proliferation and migration by inhibiting METTL3, and also promoted cell apoptosis and arrest the cell cycle in S phase. In addition, STM2457 could inhibit tumor growth in subcutaneous xenotransplantation mouse model. Our findings suggested that STM2457 had great potential for the treatment of GC and could serve as a foundation for future clinical applications.by Elisabeth G. van der Hulst, Kenneth Meijer, Pieter Meyns, Christopher McCrum
Training fall-resisting skills can prevent falls in older adults. These fall-resisting skills include proactive gait adaptability, gait robustness, and reactive gait recovery, which allow people to effectively avoid, resist, and recover from balance threats, respectively. This pilot study guided the design of an RCT of fall-resisting skills training by investigating key design factors, such as the design of a placebo-control group, obstacle difficulty settings, exploring evaluation methods for gait robustness, testing the effect of task unpredictability on anxiety, and the general feasibility. Eleven healthy older adults performed non-task-specific “placebo” balance tasks and assessment and training tasks for each fall-resisting skill. Placebo tasks included static weight-shifting exercises and dual-task walking. For the fall-resisting skill tasks, participants walked on a treadmill under different conditions. For proactive gait adaptability, participants avoided projected obstacles varying in size, approach speed, and available response time. Gait robustness was assessed using perturbations of increasing magnitude, where the margin of stability following each perturbation was compared with participants’ perceived balance loss and researchers’ observations. For reactive gait recovery, perturbations with increasing unpredictability were applied, after which participants reported their anxiety scores. Weight-shifting tasks were perceived as balance training by most participants, indicating their potential as placebo tasks. Obstacle avoidance difficulty increased most with fast approach speed and large obstacle sizes. A margin of stability-based threshold did not consistently align with perceived balance loss or observer judgement. Anxiety did not increase with more unpredictable perturbation tasks when introduced gradually. Fall-resisting skill tasks generally were feasible for older adults.by Claudia N. Spaan, Eileen Daniels, Wouter L. Smit, Ruben J. de Boer, Joana Silva, Jacqueline L. M. Vermeulen, S. Meisner, Vanesa Muncan, Riekelt H. Houtkooper, Jarom Heijmans
Reprogramming of energy metabolism is one of the hallmarks of cancer cells and mutations that modify wild type intestinal cells to colon carcinomas increases cellular energy expenditure. Mitochondria are the main site for ATP production in (cancer) cells and disrupting their function results in impaired tumor forming efficacy. The mitochondrial ribosomal proteins (MRPs) constitute the ribosome specifically in mitochondria, and as such are crucial for the translation process of the electron transport chain complex subunits. We hence aimed to explore the consequence of reduced MRP expression on adenomagensis and investigate this in a genetic mouse model with bodywide heterozygosity for Mrpl54. We show that Mrpl54 heterozygosity does not alter adenoma formation, intestinal proliferation or apoptosis in a heterozygous Apc model. Furthermore, diminished Mrpl54 expression did not decrease stemness or global parameters of metabolism in colorectal cancer cell lines.by Qiaoling Li, Jing Zhang, Shasha Meng, Fengxiang Tian, Qinqin Mei, Hui Wang, Hong Qi
BackgroundSelf-regulated fatigue is often assessed in studies of chronic diseases. Research is needed on the self-regulation of fatigue and physical activity in lung cancer patients undergoing treatment, and the impact of these factors on this population.
ObjectiveThe goal of this study is to investigate the current status, influencing factors, and correlation between self-regulatory fatigue and physical activity in lung cancer patients undergoing comprehensive treatment.
MethodsWe used a convenience sampling method to enroll 188 lung cancer patients admitted to two tertiary hospitals in Chengdu from October 2024 to April 2025. Data were collected using a general information questionnaire and two scales: the Self-Regulatory Fatigue Scale (SRF-S) and The International Physical Activity Questionnaire-long form (IPAQ-L).
ResultsThe mean self-regulatory fatigue score was 42.19 ± 9.06. The total metabolic equivalent (MET) of physical activity was 544.00 (0.00, 1386.00) MET-min/week, with leisure-time activity accounting for 429.00 (0.00, 1188.00) MET-min/week (data presented as median and interquartile range). Significant negative correlations were observed between Self-Regulatory Fatigue total scores and energy expenditure from housework, leisure activities, as well as total physical activity expenditure. Furthermore, self-regulatory fatigue was negatively correlated with both moderate-intensity and low-intensity physical activity, but positively correlated with high-intensity physical activity (P P R² = 0.306).
ConclusionEngaging in appropriate leisure and household activities at moderate-to-low intensity may help alleviate the severity of self-regulatory fatigue in lung cancer patients undergoing comprehensive treatment. Healthcare providers should encourage appropriate activity to reduce the psychological burden and conserve self-regulatory resources.
by Yonggang Chen, Jintai Luo, Yingying Zheng, Xiaomei Jiang, Zixiang Yang, Xiaobing Liu
BackgroundDiabetic kidney disease (DKD) poses a significant health burden with inadequate diagnostic sensitivity. This study develops non-invasive biomarkers by integrating urinary and renal single-cell sequencing with machine learning.
MethodsThis study analyzed DKD single-cell and bulk transcriptomic data from public repositories. We established a computational pipeline to distinguish kidney-originating cells in urinary sediments, enabling the identification of injury-associated gene signatures. These signatures were refined using machine learning to develop a diagnostic model, which was validated in independent cohorts. The biomarkers were further verified in DKD renal tissues at single-cell resolution and across multiple nephropathies. Functional and spatial analyses confirmed biological relevance using transcriptomic and histological validation.
ResultsSingle-cell analysis of 2,089 urine-derived cells identified eight renal cell types, including injured proximal tubule cells (Inj-PTC) showing upregulated injury markers (HAVCR1, VCAM1) and enriched apoptotic/TGF-β pathways. A machine learning-selected biomarker panel (PDK4, RHCG, FBP1) demonstrated strong diagnostic value (area under the curve, AUC > 0.9), with consistent downregulation across multiple chronic kidney diseases. PDK4 and FBP1 were specifically suppressed in DKD renal Inj-PTC (p Conclusions
This study identifies a three-gene biomarker panel (PDK4, RHCG, FBP1) as a promising non-invasive diagnostic tool for DKD. While demonstrating excellent diagnostic performance. It represents a tubular injury-associated gene signature that is detectable in urinary cells and shows strong association with DKD in transcriptomic datasets, presenting a promising candidate for a non-invasive diagnostic assay.
by Lei Guo, Jun Ge, Li Cheng, Xinyi Zhang, Zhengzheng Wu, Meili Liu, Hanmei Jiang, Wei Gong, Yi Liu
BackgroundThe incidence of ulcerative colitis (UC) remains high, with an increasing prevalence among elderly patients. Cellular senescence has been widely recognized as a contributor to UC susceptibility; however, the underlying molecular mechanisms remain incompletely understood. This study aimed to identify senescence-associated biomarkers in UC to provide new insight for diagnosis and treatment.
MethodsBy integrating transcriptomic data from UC patients with established aging-related databases, we identified aging-associated differentially expressed genes (DEGs). Using weighted gene co-expression network analysis (WGCNA) and Cytoscape, we pinpointed the core genes involved. A diagnostic model for UC was then developed based on these core genes, and their expression patterns were characterized at single-cell resolution. The roles of these genes were ultimately validated through in vitro and animal experiments.
ResultsWe identified 24 aging-related DEGs in UC, which were primarily implicated in inflammatory responses and cytokine-receptor interactions. Further analyses pinpointed three core genes (CXCL1, MMP9, and STAT1) that were predominantly expressed in macrophages. A diagnostic model constructed using these genes exhibited robust predictive performance. Experimental validation confirmed that the expression levels of all three core genes were significantly upregulated in both a UC mouse model and in macrophages compared to controls. Additionally, pathway analyses revealed elevated levels of CXCL12 and VEGFA in the enriched pathways.
DiscussionOur findings underscore the pivotal roles of CXCL1, MMP9, and STAT1 in UC-associated cellular senescence. The analysis positions these molecules as promising macrophage-mediated diagnostic biomarkers and therapeutic targets. Collectively, this work provides novel insights into UC pathogenesis and lays a foundation for developing precision medicine strategies that target senescence pathways.
by Seungjae Cho, Nancy Xi, Emma A. Bateman, Cynthia Chui, Eric Poon, Aran Bains, Patrick Fangping Yao, Meiqi Guo
ObjectiveThe purpose of this scoping review is to map the existing evidence that describes strategies to improve handover from the acute care to rehabilitation settings.
IntroductionPoor handover processes have been associated with preventable errors, delays in care, and adverse patient outcomes. Effective physician-to-physician handover during transitions of care is critical to ensuring patient safety and optimizing clinical outcomes. Physician handover between acute and rehabilitation care settings is particularly complicated, as it requires transferring detailed and timely information for continuity of care for medically and/or surgically complex patients between components of healthcare systems with different cultures and goals of care. Despite numerous studies being published on handover, there has yet to be a synthesis of the existing literature that seeks to explore handovers across acute to rehabilitation settings as well as how care transitions can be improved. This scoping review aims to map the existing evidence on physician-to-physician handover from acute care to rehabilitation.
MethodsThis review will be conducted following the Joanna Briggs Institute (JBI) framework and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines. A comprehensive search will be performed across the following electronic databases: MEDLINE(R) ALL (Ovid), Embase Classic + Embase (Ovid), APA PsycINFO (Ovid), Cochrane Central Register of Controlled Trials (Ovid), Emcare (Ovid), CINAHL Ultimate (EBSCO) and Web of Science (Clarivate). All rounds of screening, data extraction, and data synthesis will be conducted independently with each stage performed in duplicate. The extracted data will be summarized both quantitively with descriptive statistics and qualitatively using content analysis.
Eligibility CriteriaQualitative and quantitative studies published in English that discuss physician-physician handover from acute care to rehabilitation settings will be included. All geographical areas will be considered. Case reports, case series, commentaries, protocols, opinion pieces (editorials), or abstracts from conferences will be excluded.
by Darren Curnoe, Mohammed S. Sauffi, Hsiao Mei Goh, Xue-feng Sun, Roshan Peiris
The rarity of Late Pleistocene hominin remains from Insular Southeast Asia (ISEA) has hampered our ability to understand a crucial episode of human evolutionary history, namely, the global dispersal of Homo sapiens from Africa. Moreover, recent discoveries indicate a surprising level of taxic diversity during this time with at least two species—H. floresiensis and H. luzonensis—endemic to the region when H. sapiens first arrived. A third hominin dubbed the ‘Denisovans’ is shown from DNA evidence to have interbred with the ancestors of contemporary Indigenous populations across ISEA, New Guinea and Australia. Yet, the Denisovans have not been identified from the fossil record of the area despite recent breakthroughs in this regard on mainland East Asia. New excavations by our team at the Trader’s Cave in the Niah National Park (‘Niah Caves’), northern Borneo, have yielded an isolated hominin upper central permanent incisor dated with Optically Stimulated Luminescence dating of sediments to about 52 − 55 thousand years ago. Specimen SMD-TC-AA210 has a massive crown absolutely and relative to its root size, the crown is wide (mesiodistally) and relatively short (labiolingually). Morphologically, it exhibits a very strong degree of labial convexity, pronounced shovelling, and the bulging basal eminence exhibits several upward finger-like projections. Labial enamel wrinking on the enamel-dentine junction is expressed as two large ridges exhibiting numerous spine-like projections, and the lingual extensions on the enamel surface of the basal eminence are expressed as six extensions. This combination of crown size and morphological traits is not normally found in H. sapiens and instead characterises archaic members of Homo such as H. erectus, H. neanderthalensis and Middle Pleistocene hominins sharing a clade with H. heidelbergensis. The Trader’s Cave tooth suggests that an archaic hominin population inhabited northern Borneo just prior to or coincident with the arrival of H. sapiens as documented at the nearby West Mouth of the Niah Great Cave.by Ryan D. Parsons, Sarah Bauermeister, Julian Turner, Natalie Coles, Simon Thompson, Emma Squires, Tracey Riseborough, Joshua Bauermeister, Abbie Simpkin, Naomi French, Shankly Cragg, Hazel Lockhart-Jones, Olly Robertson, Abhaya Adlakha, Ian Thompson, John Gallacher
Adolescent mental health and wellbeing are of growing concern globally with increased incidence of mental health disorders in young people. BrainWaves provides a framework for relevant and diverse research programmes into adolescent mental health and wellbeing that can translate into practice and policy. The research programme is a partnership with schools centred on establishing a large (n > 50,000) cohort and trials platform. Reported here is the BrainWaves cohort pilot study. This was designed as proof-of-concept for our recruitment and data capture pipelines, and for cost-modelling. A network of research schools was recruited and a computer-driven questionnaire administered. The eligible population was 16 + year olds who were attending the research schools. Of 41 research schools, 36 (88%) participated over one three-week and one four-week data collection period. From an eligible population of 33,531 young people, 16,010 (48%) attended the study lesson and created an account. Of the 16,010 (100%) who created an account, 15,444 (96%) consented to participate, 9,321 (60%) consented to linkage of research data with educational records, and 6,069 (39%) consented to linkage of research with school/college attendance data. Participants were aged 16–19 years, 59% female, and 76% White. Higher levels of anxiety and depression were found in females than males. Higher levels of media-based social networking were found in females, whereas higher levels of media-based gaming were found in males. Females were more likely to report insufficient sleep whilst males were more likely to report high levels of exercise. This study confirmed an ability to recruit at pace and scale. Whilst the response-rate does not indicate a representative sample, the demographics describe an inclusive and diverse sample. Data collected confirmed findings from previous studies indicating that the electronic data collection methods did not materially bias the findings. Initial cost-modelling suggests these data were collected for around £20 per participant.by Matheus de O. Costa, Roman Nosach, Maite H. M. de Almeida
Porcine ear necrosis (PEN) (also referred to as ear-tip necrosis, ETN) is a syndrome of global presence and unclear aetiology. Initially reported in the 1950s, many different infectious and non-infectious causes have been suggested as the causative(s) agent(s), but none has been confirmed in controlled studies. Here, we investigated the aetiology of PEN using pure culture of bacteria associated with lesions in controlled animal trials. A commercial farm with no history of ear-tip necrosis was identified and used as the source for 5-week-old pigs. Two independent trials were initially executed with identical designs. Piglets (=12/trial) were intradermally inoculated with either pure cultures of Staphylococcus hyicus or Fusobacterium necrophorum (left ear, n = 10) or sterile media (right ear, n = 10). Two pigs in each trial were not inoculated, serving as sentinels. A third trial used F. necrophorum as the inoculum, 3 pigs as sentinels and 9 as inoculated. All animals were clinically monitored daily following challenge, and an ear score was used to follow disease progression. All ears inoculated with S. hyicus remained lesion free. Four out of ten and 7/9 pigs challenged with F. necrophorum developed lesions undistinguishable from PEN, including necrosis and loss of portions of the ear pinna (P F. necrophorum was isolated from 4/10 and 7/9 pigs that developed necrotic lesions. Histopathology after resolution of necrosis revealed granulomatous tissue. Evidence presented here suggests that F. necrophorum causes PEN-like lesions, as seen in commercial barns. It is therefore suggested as the etiological agent of this syndrome.
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