Preterm birth before 28 weeks remains a leading cause of neonatal mortality and long-term morbidity. Intrauterine infection-driven chorioamnionitis is strongly associated with preterm labor, fetal inflammatory response syndrome, and neonatal lung disease. Ureaplasma species are among the most common organisms isolated in chorioamnionitis and are frequently detected in the placenta, amniotic fluid, and respiratory tract of preterm infants. Clinical and experimental data implicate Ureaplasma exposure in early lung inflammation, impaired alveolar development, and bronchopulmonary dysplasia (BPD), yet the pathogenic events preceding microbial invasion of the amniotic cavity or fetal tissues remain poorly defined. To characterize early intrauterine and fetal lung inflammatory responses to localized choriodecidual U. parvum infection, we used a chronically catheterized pregnant rhesus macaque (Macaca mulatta) model. Time-mated animals underwent surgical placement of maternal, amniotic, and choriodecidual catheters and were inoculated with low-passage U. parvum serovar 1 or vehicle control at approximately 117 days gestational age. Placenta, fetal membranes, fetal plasma, and fetal lungs were assessed by qRT-PCR, multiplex cytokine assays, immunoblotting, immunohistochemistry, and trichrome staining to evaluate inflammatory signaling, inflammasome activation, prostaglandin pathways, immune cell infiltration, fibrosis, and lung maturation markers. Choriodecidual infection was confirmed in all inoculated animals. Amniotic fluid remained culture-and PCR-negative, and fetal lungs were largely free of detectable bacterial DNA. Despite the absence of intra-amniotic infection, fetal lung cytokine profiling revealed broad pro-inflammatory activation, with elevated GM-CSF, IL-1β, IL-6, IL-8, MIP-1α/β, MCP-1, VEGF and reduced IL-10 contrasting with a modest systemic response limited to elevated plasma IL-18. Fetal lungs showed increased immune cell infiltration, upregulation of NLRP3, PYCARD, and CASP1, and activation of SAPK/JNK and NF-κB signaling. Histopathology demonstrated increased alveolar macrophages and intra-alveolar neutrophils with minimal fibrosis. Surfactant gene expression was altered (increased SFTPA , decreased SFTPB), and elevated α-SMA indicated early myofibroblast activation. Localized choriodecidual U. parvum infection induces fetal lung inflammation prior to detectable intra-amniotic infection, demonstrating that direct infection of the amniotic fluid or fetal lung is not required for the initiation of fetal pulmonary inflammation. These findings suggest that subclinical ascending infection may initiate fetal lung injury and increase susceptibility to postnatal respiratory morbidity associated with preterm birth.

Diffuse large B-cell lymphoma (DLBCL) most commonly arises in nodal regions but may also present extranodally. We report two cases of large B-cell lymphoma developing in postpneumonectomy cavities more than a decade after surgery for primary lung carcinoma. In both patients, no history of systemic immunodeficiency, organ transplantation, or chronic immunosuppressive therapy was present, and HIV, hepatitis B, and hepatitis C serologies were negative. In Case 1, the lymphoma showed an activated postgerminal center phenotype and was negative for EBER and HHV-8. In Case 2, the tumor was CD20-negative and EBER-positive, with pathological features of inflammation-associated large B-cell lymphoma. PET-CT was used for staging and response assessment in both patients, and both achieved complete metabolic remission after curative-intent chemotherapy. These cases underscore a rare clinical entity that differs pathophysiologically from pyothorax-associated lymphoma (PAL) or primary effusion lymphoma (PEL). They highlight the postpneumonectomy cavity as a rare but potentially permissive microenvironment for large B-cell lymphomagenesis and underscore the biological heterogeneity of these presentations.

Catheter ablation from the epicardial space is increasingly utilized to treat ventricular tachycardias (VTs). We report a rare complication.

Oral squamous cell carcinoma (OSCC) is a major global health concern, especially in India, where it is one of the primary causes of cancer-related fatalities. OSCC is notorious for its propensity to spread to distal sites such as the lungs, bones, and liver, but malignant pleural effusions resulting from OSCC are extremely uncommon. This case report details an unusual presentation of OSCC in a 61-year-old male presenting with bilateral malignant pleural effusion from a primary buccal mucosa squamous cell carcinoma with no lung involvement. Through cytological analysis and immunocytochemistry, we confirm the diagnosis of metastatic squamous cell carcinoma, highlighting the significance of comprehensive diagnostic approaches.

In this paper, we investigated the structure of a ruthenium(II) complex bearing a limonene-derived amino-oxime ligand using UV-Vis and FT-IR spectroscopy. The compound exhibited potent anticancer activity, with IC50 values up to 12 times lower than those of cisplatin against PC-3 (prostate), A-549 (lung), and HeLa (cervical) cancer cell lines. Density Functional Theory (DFT) and Time-Dependent Density Functional Theory (TD-DFT) calculations were performed using the B3LYP and PBE0 hybrid functionals. The theoretical results were compared with the experimental data, and the optimized molecular geometry, along with the simulated UV-Vis and FT-IR spectra, showed excellent agreement with the experimental observations. Notably, the PBE0 functional demonstrated slightly better consistency, highlighting its suitability for modelling the structural and spectroscopic properties of the complex. Further analyses were carried out to elucidate the electronic structure and reactivity of the Ru(II) complex, including global reactivity descriptors, frontier molecular orbital (FMO) analysis, Mulliken charge distribution, and molecular electrostatic potential (MEP) mapping, as well as electron localization function (ELF) and localized orbital locator (LOL) analyses. Molecular modelling studies were also conducted to investigate the interaction between the Ru(II) complex and human serum albumin (HSA). Molecular docking, performed through 100 independent runs, revealed two representative binding poses within the principal drug-binding cavity, selected from the dominant (63%) and secondary (34%) clusters. To evaluate the stability of these binding modes, 100 ns molecular dynamics (MD) simulations were carried out. Both poses exhibited stable interaction patterns, confirming the consistent binding of the Ru(II) complex to HSA. Overall, the computational findings are in strong agreement with the experimental data, supporting the proposed binding mechanism and further highlighting the therapeutic potential of this ruthenium-based complex as a promising anticancer candidate.

Epidemiological and experimental studies suggest wildfire smoke is a potential contributor to neurological dysfunction and associated with neuroinflammation. Using doses comparable to those encountered during intense wildfire events (200-300 μg/m[3]), we explore the absorption, distribution, metabolism, and elimination (ADME) and pharmacokinetics of representative members of major chemical classes (acid, phenol, PAH, aldehyde) in inhaled wood smoke condensates. Male Sprague Dawley rats were intranasally instilled with smoldering eucalyptus woodsmoke extract (WSE) reconstituted in saline spiked with [14]C-labeled palmitic acid (PA), benzo[a]pyrene (B[a]P), catechol (CAT) or benzaldehyde (BZ). Serum was collected from 5 min to 2 weeks after exposure and tissues were collected at 0.5, 2, 4, 24 h and 2 weeks after exposure. Urine was collected over the 24 h exposure. Tissues were collected, rinsed in PBS and analyzed by accelerator mass spectrometry (AMS) for [14]C-labeled chemicals. PA and B[a]P entered circulation slowly, reached maximum concentration (Cmax) near 15 ng/mL at 2 h, and had circulating concentrations near 1/3 Cmax 24 h after exposure. CAT and BZ rapidly entered circulation and were mostly cleared at 2 h. Excess [14]C from all four chemicals was detected in olfactory bulb and brain over the first 24 h but only PA (or its metabolites) was retained in olfactory bulb, brain and kidney at 2 weeks post exposure. All excess [14]C was cleared from the lung at 2 weeks. Metabolite analysis of urine (CAT, BZ and B(a)P) dosed samples did not detect any parent compound. CAT and BZ were rapidly cleared. The slower uptake and clearance of PA or B[a]P or their reactive metabolites when dosed with WSE in brain and olfactory bulb potentially provide greater opportunity for inflammatory response. This study suggests that wildfire smoke chemicals can enter the brain directly from the nasal cavity to the olfactory bulb and via systemic circulation.

Secondary spontaneous pneumothorax (SSP), particularly when complicated by a persistent air leak, is an uncommon but serious manifestation of active pulmonary tuberculosis. Such cases often require pleural drainage or surgical intervention. Management becomes significantly more challenging when patients present with extensive pulmonary disease, compromised general condition, and severe comorbidities. We describe a 28-year-old male with bilateral extensive pulmonary tuberculosis, persistent right-sided pneumothorax, and a severe acute flare of chronic hepatitis B. Conventional management, including pleural drainage and chemical pleurodesis, was unsuccessful, and the patient's acute hepatic injury precluded the use of standard first-line anti-tuberculosis therapy. The primary clinical dilemma involved balancing the need for surgical repair of the persistent air fistula against the prohibitive perioperative risks posed by his hepatic dysfunction and poor systemic condition. A conservative, individualized medical strategy-comprising modified anti-tuberculosis therapy, supplemental oxygen, nutritional optimization, and comprehensive liver support-was selected. Over 6 months, the patient demonstrated progressive improvement in hepatic function and overall physical status, substantial radiologic recovery of pulmonary lesions, and complete resolution of the right pneumothorax. This case highlights that a carefully tailored, conservative medical approach may yield favorable long-term outcomes in SPP secondary to pulmonary tuberculosis, particularly in patients with significant surgical contraindications. Optimizing anti-tuberculosis therapy remains central to promoting lung parenchymal healing and resolving pneumothorax.

A hyperporous polymer-based quartz crystal microbalance (QCM) chemosensor was developed for the selective determination of the signature peptide ELPLYR, a clinically significant biomarker for the prognosis of small-cell lung cancer. The sensor consists of an ELPLYR-imprinted poly(3,4-ethylenedioxythiophene) (PEDOT) recognition film electrosynthesized on gold-sputtered quartz (Au/quartz) transducers. Synthetic receptor-like cavities for ELPLYR were embedded within the PEDOT matrix using molecular imprinting. Hierarchical hyperporous networks of imprinted (MIP) and reference (REF) polymer films were fabricated using self-assembled, crystal-lattice-like sacrificial templates of amine-modified latex beads (LB-NH2). Imprinting of ELPLYR was achieved via electropolymerization of 3,4-ethylenedioxythiophene (EDOT) and functionalized monomers (EDOT-OH and EDOT-NH2) on the ELPLYR-modified, LB-NH2-coated Au/quartz surface. [1]H NMR spectroscopy, molecular dynamics, and docking simulations confirmed strong hydrogen-bonding interactions between ELPLYR and the functional monomers in the prepolymerization solution. Selective extraction of the LB-NH2 beads and the ELPLYR template yielded a hyperporous network with surface-confined imprinted cavities. Microscopic (SEM and profilometry), electrochemical (CV and EIS), and spectroscopic (XPS and RAIRS) characterization revealed a uniformly grown, permeable, and long-range ordered PEDOT film (approx. 0.3 μm thick) with interconnected cavities maintained over millimeter scales. QCM measurements under flow injection analysis (FIA) conditions demonstrated the highly selective binding of ELPLYR to the hyperporous structure (MIP-Np-S + B). The sensitivity was found to be 166.51 ± 22.35 Hz/mM (R[2] = 0.998), which is more than 5-fold higher than that of the nonimprinted analogue (REF-Np, 33.06 ± 1.47 Hz/mM, R[2] = 0.997). The sensor exhibited excellent cross-reactivity, selectively detecting ELPLYR over structural interferents such as Z-ELPLYR (73.30 ± 3.91 Hz/mM) and a constituent amino acid cocktail (11.37 ± 2.23 Hz/mM). Furthermore, the sensor successfully recognized ELPLYR in artificial cerebrospinal fluid. Under optimized FIA conditions, the linear dynamic range extended from 39 ng/mL to 450 μg/mL (R[2] = 0.998), with a limit of quantitation of 78 ng/mL (S/N = 5). Finally, the platform detected the signature peptide in blood and digested serum samples (100 ng/mL) collected via quantitative dried blood spot cards, demonstrating its potential for on-site sampling and clinical diagnostics. This work highlights the critical role of hierarchical nanostructures in enhancing chemosensor performance and the feasibility of peptide detection in complex biological fluids.

The emergence of drug resistance and off-target toxicities in epidermal growth factor receptor (EGFR) targeted therapies underscores the urgent need for novel inhibitor scaffolds. This study integrates artificial intelligence-driven generative models with experimental validation to discover novel, selective EGFR inhibitors. Utilizing REINVENT4, a reinforcement learning-based generative framework, we performed a stage-wise, multi-objective optimization using a curated dataset of active EGFR inhibitors. The optimization was guided by a composite reward function incorporating docking scores, and quantitative estimates of drug-likeness (QED) and synthetic accessibility (SAscore). Candidate molecules were subsequently evaluated using molecular dynamics (MD) simulations, synthesized, and subjected to in vitro kinase and cellular assays. The generative pipeline successfully converged on a promising N-(quinolin-5-yl) benzenesulfonamide scaffold. Among the synthesized candidates, Hit1 exhibited potent in vitro EGFR kinase inhibition (IC50 = 21.22 nM), although ~ 19-fold less potent than Gefitinib. MD simulations analyses revealed that hydrogen bond interactions with Lys745 and proper occupation of the Val726 hydrophobic cavity are critical for binding. Notably, Hit1 demonstrated robust, targeted anti-proliferative activity against EGFR-mutant non-small cell lung cancer (NSCLC) cells (PC9 and HCC827), while displaying strong selectivity over wild-type EGFR cells (A549). Our findings validate the efficacy of a target-aware reinforcement learning approach for de novo drug design. The discovered quinoline-sulfonamide derivative represents a highly promising, synthetically tractable lead compound for the development of next-generation mutation-selective EGFR inhibitors.

Pulmonary tuberculosis typically exhibits characteristic imaging findings; however, radiological manifestations can be atypical in certain cases, leading to potential misdiagnosis based solely on CT imaging. We describe a 59-year-old man who developed a 4-month history of cough and a 2-week fever during postoperative radiotherapy following esophagectomy for esophageal cancer. CT scans revealed multiple, scattered cystic cavities in both lungs, characterized by regular shape and well-defined borders. Following anti-tuberculosis therapy, the pre-existing cystic cavities collapsed and evolved into nodular opacities, a change highly suggestive of cystic metastases given the patient's history of esophageal cancer. A biopsy confirmed granulomatous inflammation, and follow-up at eight months after the initiation of anti-tuberculosis therapy showed near-complete resolution of the lesions. Although cystic pulmonary tuberculosis is rarely reported, this case is notable for its distinct cystic characteristics. To our knowledge, this is the first case to systematically document the transformation of cystic lesions into nodules during anti-tuberculosis therapy-a finding that may raise suspicion for cystic metastases and highlights the diverse and atypical radiological manifestations of tuberculosis in immunocompromised hosts.

Survivors of tuberculosis (TB) often develop structural lung damage, including fibrosis, cavities, and bronchiectasis, which may predispose them to secondary infections such as pulmonary aspergillosis. Using data from Korea's Healthcare Big Data platform, which integrates information from the Korea National Health Insurance Service and the Korea Centers for Disease Control and Prevention, we conducted a retrospective cohort study including 13,653 TB survivors and 40,959 matched controls without a history of TB. During a median follow-up of 5.4 years, the incidence of pulmonary aspergillosis was markedly higher among TB survivors than controls (0.89 vs. 0.09 per 1,000 person-years; p < 0.001), corresponding to an adjusted hazard ratio (aHR) of 6.84 (95% confidence interval [CI], 3.89-12.1). Among TB survivors, low body mass index (aHR, 2.06; 95% CI, 1.11-3.82), diabetes mellitus (aHR, 4.45; 95% CI, 2.56-7.73), connective tissue disease (aHR, 23.19; 95% CI, 2.99-179.63), and bronchiectasis (aHR, 2.55; 95% CI, 1.08-6.04) were independently associated with pulmonary aspergillosis. These findings indicate that TB survivors are at a substantially increased risk of pulmonary aspergillosis, underscoring the need for long-term surveillance and risk-based management strategies in this high-risk population.