Nosocomial meningitis is a serious complication of neurosurgical procedures, associated with high morbidity and mortality, as well as significant diagnostic and therapeutic challenges. Among the causative pathogens, Acinetobacter baumannii (A. baumannii) is particularly concerning due to its ability to survive for prolonged periods in the hospital environment, its opportunistic virulence, and, especially, its tendency to develop multidrug resistance to antimicrobial agents. Diagnosis is often difficult in the postoperative setting, particularly when the cerebrospinal fluid (CSF) is altered as a result of the surgical procedure. Rapid identification of the causative agent and early initiation of appropriate antibiotic therapy are essential to limit complications and improve patient prognosis. We report the case of a 27-year-old patient with a history of surgically treated craniopharyngioma complicated by anterior hypopituitarism. Three weeks after surgery, he was admitted to the ICU with suspected postoperative meningitis due to the onset of behavioral disturbances associated with nasal discharge, without a fever. Brain CT was normal. CSF analysis, obtained by lumbar puncture under strict aseptic conditions, revealed a turbid fluid with leukocytosis of 5,760 cells/mm[3], predominantly composed of neutrophils, along with elevated protein levels (5.7 g/L) and low glucose levels (0.05 g/L). Direct examination after Gram staining showed Gram-negative coccobacilli with a marked inflammatory reaction. CSF culture grew a multidrug-resistant (MDR) strain of A. baumannii, which was sensitive only to colistin. The patient received antibiotic therapy with colistin, administered intravenously and intrathecally for 18 days, with initial neurological improvement and sterilization of the CSF by the 15th day of treatment. The subsequent course was unfavorable, marked by the development of acute respiratory distress syndrome (ARDS) secondary to ventilator-associated pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA), complicated by refractory septic shock, which ultimately led to his death after one month of hospitalization in the ICU. This report highlights the severity of nosocomial meningitis caused by MDR A. baumannii and underscores the importance of implementing infection prevention measures in healthcare settings.

Lysosome-dependent cell death (LDCD) is a distinct mode of regulated cell death, which differs from canonical cell death pathways such as apoptosis and necrosis. Its key features include lysosomal membrane permeabilization and the downstream signaling cascades triggered by cathepsin release. Recent studies have demonstrated that LDCD exerts dual, intricate influences on cancer initiation, progression, immune homeostasis and therapeutic responses. It not only confers a survival advantage upon cancer cells but also represents a promising target for targeted antitumor therapy. This review systematically summarizes the molecular mechanisms underlying LDCD, its dual regulatory roles in cancer, and LDCD-based anticancer therapeutic strategies, and outlines future research directions. Ultimately, this work sheds light on the mechanistic link between LDCD and oncogenesis, providing a rationale for the development of targeted antitumor strategies.

Renal cell carcinoma (RCC) is the third most prevalent urological malignancy, characterized by histological heterogeneity and complex molecular landscapes. Although established regimens, including surgical intervention, targeted therapies and immunotherapy, effectively manage early-stage disease, patients with advanced RCC still have a poor prognosis. The expanding spectrum of regulated cell death (RCD), ranging from established apoptosis and ferroptosis to emerging modalities like cuproptosis, disulfidptosis and ammonia-induced cell death, offers novel mechanistic insights into tumor vulnerabilities. This tumor progression and subsequent therapeutic resistance are substantially mediated by dysregulated networks of RCD. To systematically deconstruct this mechanistic complexity, this review stratifies RCD into three specific functional dimensions: precise protein signaling, intracellular homeostasis dysregulation, and physiological dysfunction. Because RCC intrinsically evades cascade-governed pathways such as apoptosis to survive immune elimination, its inherent metabolic reprogramming concomitantly creates paradoxical vulnerabilities. Consequently, these tumors exhibit profound susceptibility to homeostasis-disrupting modalities like ferroptosis, cuproptosis, disulfidptosis, and ammonia-induced cell death. Extending this mechanistic framework beyond clear cell RCC (ccRCC), we define the unique metabolic and redox dependencies of underrepresented non-clear cell variants, including papillary RCC (pRCC), chromophobe RCC (chRCC), fumarate hydratase (FH)-deficient RCC and TFE3-rearranged RCC. By evaluating current RCD-targeted pharmacological interventions, this review highlights critical opportunities to exploit these functional dependencies, offering rational approaches to overcome intrinsic resistance and complement existing therapies. Ultimately, integrating this multidimensional RCD framework with multi-omics profiling facilitates a deeper biological understanding of renal tumors and provides a necessary foundation to accelerate the development of precision oncology.

The COVID-19 pandemic severely disrupted routine immunization globally and across Cameroon, causing a surge in 'zero-dose' (ZD) children and exacerbating 'missed opportunities for vaccination' (MOV). This necessitated accelerated recovery initiatives like the Big Catch-Up (BCU). This study explores BCU's operationalization, implementation and sustainability in Cameroon, assessing how vertical funding interacted with national health systems to reach ZD and under immunized (UI) children. Focusing on four districts (urban, conflict-affected, isolated island, and remote rural), we triangulated data from 34 document reviews (e.g., national policies, operational plans, budget frameworks, and EPI reports), 37 key informant interviews across all health system levels, and 11 Focus Group Discussions (FGD) with 86 community stakeholders, including caregivers. Thematic analysis reveals that while BCU remained a campaign-style intervention with parallel reporting structures, its funding acted as a critical accelerator to operationalize Cameroon's pre-existing but under-implemented 2021 National Policy and Guidelines on Catch-up Immunization. However, centralized financial control created top-down pressures that were mitigated through bottom-up co-creation during local micro-planning. Operationally, reducing MOV required a shift from passive screening to active 'Catch and Vaccinate' models, necessitating context-specific delivery adaptations in conflict zones and island populations. Despite these operational successes, stakeholders expressed deep concern regarding the long-term institutionalization due to an impending fiscal cliff. The system's heavy reliance on external donor financing threatens the sustainability of Community Health Workers' (CHW) incentives essential for demand generation. Furthermore, while the parallel IASO digital platform enabled real-time geolocation of missed children, it created double-reporting burdens, highlighting the structural challenge of synchronizing campaign tools with the national routine health information system. Ultimately, while recovery funding can successfully catalyze national policies and drive immediate equity gains, sustained resilience requires an urgent transition to domestic financing, the embedding of adaptive service delivery models into routine primary care, and the harmonization of digital tracking systems.

T(6;11) translocation renal cell carcinoma (RCC) is a distinct renal tumor distinguished by the generation of Alpha-TFEB fusion gene. TFEB is highly expressed in this subtype and may drive its progression. However, its underlying mechanism remains incompletely elucidated. The current study is intended to explore whether TFEB promotes the progression of t(6;11) translocation RCC by regulating long intergenic non-protein coding RNA (LINC)00612 expression. HK-2-TFEB and Caki-2-TFEB were stably transfected cell lines with Alpha-TFEB fusion gene, which were successfully established in our research group's previous work. Western blotting was carried out to assess TFEB protein expression, and qRT-PCR was employed to measure LINC00612, microRNA (miR)-31-5p and CTNNB1 expression levels. Bioinformatics analysis, dual-luciferase reporter and chromatin immunoprecipitation (ChIP) assays were employed to validate the interactions between TFEB and LINC00612, LINC00612 and miR-31-5p, as well as miR-31-5p and CTNNB1. Wound healing, CCK-8 and invasion assays were used to verify the effects exerted by LINC00612 downregulation and upregulation, as well as CTNNB1 downregulation on the biological functionalities of cells. Experiments carried out in vivo were designed to assess the effects of TFEB, LINC00612 and miR-31-5p on tumor growth. Western blotting showed high expression of TFEB in HK-2-TFEB and Caki-2-TFEB cells compared to their respective control cells. qRT-PCR revealed enhanced expression of LINC00612, decreased miR-31-5p expression and increased expression of CTNNB1 in HK-2-TFEB and Caki-2-TFEB cells. Dual-luciferase reporter and ChIP experiments confirmed that TFEB specifically bound to the promoter of LINC00612. LINC00612 overexpression in HK-2 cells enhanced cell proliferative capacity, migratory activity, and invasive potential, while its knockdown in HK-2-TFEB cells suppressed these cellular processes. LINC00612 was shown to have targeted binding to miR-31-5p, and miR-31-5p was verified to target CTNNB1. In vivo experiments demonstrated that either TFEB or LINC00612 overexpression promoted tumor growth, whereas overexpression of miR-31-5p inhibited tumor growth. Our findings suggested that overexpression of TFEB upregulated LINC00612 expression and LINC00612 competitively inhibited miR-31-5p, which directly targeted the downstream gene CTNNB1, ultimately promoting tumor progression. TFEB/LINC00612/miR-31-5p axis may be a new molecular therapeutic target for t(6;11) translocation RCC patients.

Phaeohyphomycosis is an opportunistic mycosis caused by dematiaceous fungi, typically affecting the cutaneous or subcutaneous tissues of the facial region and distal extremities in cats. This report documents a case of Cladophialophora boppii infection in a cat. A 7-year-old neutered male domestic shorthair cat was presented with a chronic, pigmented nasal lesion, non-productive sneezing, and stertor. Computed tomography, rhinoscopy, and tissue sampling were performed. Fungal culture and molecular sequencing confirmed the diagnosis. Oral itraconazole treatment failed to arrest progression, necessitating delayed nasal planectomy. Despite transient remission, disease recurred, requiring repeat surgical debridement, and prolonged antifungal treatment. Clinical resolution was ultimately achieved, with marked improvement in the cat's quality of life. Identification of a novel species of phaeohyphomycosis in a cat emphasizes the need for increased awareness of emerging fungal pathogens that can precipitate considerable morbidity, particularly in the absence of prompt aggressive intervention.

Production of good quality eggs still plagues mass propagation efforts of anguillid eels. Understanding the lipid dynamics of artificially maturing eels will inevitably benefit captive rearing practices due to the importance of lipids for egg quality. Fortnightly sampling of shortfinned eels (Anguilla australis) subjected to hypophysation for 10 weeks allowed us to gather important information relating to multiple aspects of lipid physiology. Accordingly, expected increases in gonadosomatic (from 2.20 ± 0.14 to 23.20 ± 6.01%) and hepatic somatic indices (from 0.89 ± 0.04 to 1.93 ± 0.01%), as well as oocyte diameter (from ~ 220 to ~ 700 µm) were complemented with notable increases in hepatic and ovarian vitellogenin levels at both the gene and protein levels in treated eels compared to Ringer-injected controls. A fivefold increase in hepatic expression of oestrogen receptor-alpha, but not the -beta isoform, corroborates the role for estradiol in promoting vitellogenesis. Conversely, decreases in expression of apolipoprotein b and the peroxisome proliferator-activated receptors in the liver point to a change in the role of the liver away from the neutral lipid packaging associated with previtellogenesis towards vitellogenin loading, ultimately culminating in yolk protein sequestration by the oocytes.

Secondary failure of platelet recovery (SFPR) poses a significant risk for life-threatening complications following hematopoietic stem cell transplantation (HSCT). However, the incidence, clinical outcomes, and risk factors associated with SFPR in the context of allogeneic HSCT (allo-HSCT) for pediatric patients with acquired aplastic anemia (AA) remain unclear. We conducted a retrospective review of 86 consecutive acquired AA children who underwent allo-HSCT at our center from December 2017 to November 2023. The 1-year cumulative incidence of SFPR was found to be 11.6% (95% confidence interval [CI]: 6.2%-21.1%). The median time to SFPR was 2 months (range: 1-5 months) post-transplantation. To clarify the risk factors for SFPR, 9 SFPR cases and 69 non-SFPR cases were further analyzed. Multivariable analyses revealed that age, pre-transplantation body mass index (BMI) and a history of grade Ⅲ-Ⅳ acute graft-versus-host disease (aGVHD) were the most significant predictors for SFPR post-transplantation (p < 0.05). Additionally, we found that the 2-year overall survival rate was significantly lower in children with SFPR compared to those without (74.1% vs. 96.7%; p < 0.005). Ultimately, 4 patients achieved full platelet count recovery, with 2 patients becoming transfusion-independent. However, 1 patient still requires periodic platelet transfusions, and 2 patients unfortunately died.Among the 6 patients who received thrombopoietin receptor agonist therapy, an overall response rate of 66.6% was observed, suggesting the potential efficacy of this treatment approach in managing SFPR. This study underscores the need for vigilant monitoring of platelet recovery in pediatric HSCT recipients and highlights the need for further research into the etiology of SFPR to improve clinical outcomes.

With the increasing rates of cesarean section (CS), cesarean section scar defect (CSD) has become an escalating clinical concern due to uterine dysfunction and reduced fertility. However, the biological basis of CSD remains poorly understood, particularly the mechanisms of impaired uterine repair after CS and the causes of failure in conventional repair surgeries. This study integrates metabolomics, transcriptomics, a newly developed mouse model, and functional assays to elucidate the complex interplay between senescence and fibrosis in CSD. Our findings identify upregulation of the PGES/prostaglandin E2 (PGE2) axis as a key upstream event that disrupts uterine healing. Elevated PGE2 preferentially induces early senescence of macrophages, which transmit pro-senescent signals to uterine fibroblasts through IL-1β/IL-1R signaling. This sequential senescence cascade drives excessive fibroblast activation and progressive fibrosis, ultimately impairing uterine structure and function. In mouse CS models, inhibition of the PGES/PGE2 pathway and anti-aging strategies significantly attenuate fibrosis and restore coordinated myometrial and endometrial repair. Our findings uncover a macrophage-fibroblast senescence relay to fibrotic scar formation in CSD and provide a translational rationale for targeting PGE2 signaling and senescence to improve uterine repair after CS.

Nitric oxide (NO) is a key signaling molecule regulating plant stress responses. In our study, the NO donor sodium nitroprusside (SNP) significantly promoted ginger seedling growth under salt stress, while treatment with the NO scavenger cPTIO resulted in an opposite response, supporting the involvement of NO in salt-stress responses. Transcriptome profiling of ginger leaves identified 2252 differentially expressed genes (DEGs), which were enriched in 55 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Further, analysis showed that 19 DEGs were enriched in plant hormone signal transduction, while 16 DEGs were enriched in starch and sugar metabolism. NO treatment increased the levels of indole-3-acetic acid (IAA), gibberellin 3 (GA3), and trans-zeatin (ZR), while reducing the levels of abscisic acid (ABA), methyl jasmonate (MeJA), and brassinosteroid (BR). Moreover, NO promoted the accumulation of soluble sugars and sucrose and enhanced the activities of key enzymes involved in starch and sucrose metabolism, thereby effectively improving osmotic adjustment. Collectively, NO improves antioxidant capacity, maintains endogenous phytohormone balance, and enhances osmotic adjustment, ultimately alleviating salt stress damage in ginger seedlings.

Many observational studies are interested in the total effect of physical activity on any given health outcome. These studies rely heavily on covariate adjustment, yet decisions about which variables to include vary widely. Such decisions have meaningful consequences, including altering estimated effect sizes and their interpretation, and ultimately, modifying our understanding of how physical activity influences health. For example, inclusion of biological intermediates is likely to constitute overadjustment, while the role of co-occurring health behaviors is more conceptually complex. Despite longstanding recognition of overadjustment bias, there remains little consensus regarding which variables should routinely be included in models that use observational data to explore the effect of physical activity on health. In this paper, we discuss key conceptual definitions and frameworks relevant to covariate selection, such as confounding, mediation, and overadjustment, alongside the shift from statistical toward conceptual approaches including causal inference frameworks (eg, directed acyclic graphs). We outline common biological and behavioral pathways linking physical activity to downstream health outcomes, highlighting the challenges of adjusting for biological intermediates, health-status indicators, and co-occurring health behaviors. We draw on empirical illustrations using data from cohort studies in Brazil, the United Kingdom, and the United States to explore how common adjustment strategies influence estimates of the association between physical activity and each of hypertension, type 2 diabetes, and all-cause mortality. The use of directed acyclic graphs highlights where adjustment decisions may be conceptually simple and where they require careful consideration of the underlying causal assumptions. Our findings demonstrate that adjustment decisions meaningfully influence both the magnitude and interpretation of associations in physical activity epidemiology. We conclude by proposing practical recommendations to improve transparency, interpretation, and covariate selection in future observational epidemiological analyses examining how physical activity influences health outcomes.