To maximize the impact of doxycycline post-exposure prophylaxis (doxyPEP) in controlling the bacterial STI epidemic, understanding of the barriers to delivering doxyPEP to the most vulnerable populations is essential. Guided by the COM-B (capability, opportunity, motivation, and behavior) framework, we interviewed 26 racial and ethnically diverse participants eligible for doxyPEP to identify barriers and facilitators to doxyPEP use. Participants reported facilitators such as: knowledge; positive clinical encounters; community normalization; and beliefs regarding efficacy, peer attitudes and motivations around doxyPEP. Barriers included confusion with HIV PrEP and a need for more knowledge; access to healthcare or negative experiences with healthcare; limited community awareness and concerns around disclosure. However, participants also described potential solutions, including specific knowledge needed, low barrier and non-judgmental healthcare, home STI testing, and increased community awareness and normalization.

Some long noncoding RNAs (lncRNAs) are known to regulate gene expression. However, the underlying temporal dynamics of lncRNAs influencing gene and epigenetic regulation, and mechanisms of lncRNA regulation in trans, are less understood. To investigate this, we genetically engineer 17 doxycycline-inducible lncRNA transgenes for ectopic expression at the H11 safe harbor locus in human pluripotent stem cells (hiPSCs), and we generate high-density temporal RNA-seq and ATAC-seq profiles. Most lncRNA transgenes are induced at 2 hours and maintain expression through the 96-hour time course. Surprisingly, when we seek to identify gene expression changes due to the lncRNAs, we find that the global transcriptional landscape is dominated by a strong systemic response triggered by doxycycline exposure. We rigorously define this cohort of genes as a Doxycycline-Responsive Gene Signature (DRGS). The DRGS is also present in at least 28 public datasets from dox-inducible transgene studies involving diverse cell types. Next, we determine which lncRNAs exhibit trans-regulatory events. We identify DANCR, FENDRR, LINC00667, LINC00847, LNCPRESS1, and LNCPNKY as lncRNAs that regulate specific transcript expression in trans The downstream target genes encode 53 mRNAs and 10 lncRNAs. None of the target lncRNAs alter gene expression proximal to their own loci (i.e., triggering secondary cis effects). Surprisingly, the target genes of LINC00847 (transcribed from Chromosome 22) are substantially enriched on Chromosome 19, with a preponderance of target genes encoding RNA metabolism and RNA splicing factors. Collectively, our study provides a resource to discern artifacts in the doxycycline-inducible system and identifies temporally regulated targets of 6 lncRNAs for future mechanistic studies.

M.pneumoniae is a major cause of human respiratory infection whose pathogenicity relies on adhesion proteins, secreted virulence factors, and immune evasion mechanisms. This review contextualizes these strategies within the broader phylogeny of clinically relevant Mycoplasma species while addressing the diverse extrapulmonary manifestations of M. pneumoniae. Current challenges in managing M. pneumoniae infections are multifaceted. The post-pandemic resurgence reflects a population-level immune debt resulting from prolonged non-pharmaceutical interventions, with test positivity rising sharply after restrictions were lifted and driving pneumonia outbreaks across age groups. Macrolide resistance remains persistently high in East Asia and is emerging at variable rates in other regions; routine diagnostics cannot detect resistance in real time, complicating first-line empirical therapy. Vaccine development continues to face obstacles including antigenic variation mediated by recombination between repetitive genomic sequences, the IL-17 A paradox wherein protective Th17 responses also drive vaccine-enhanced disease, and the inability of systemic vaccines to induce mucosal secretory IgA and tissue-resident memory T cells. In response, we evaluate emerging diagnostics-including metagenomic sequencing, CRISPR-Cas platforms, and host biomarkers-and discuss resistance-guided therapies involving doxycycline, quinolones, and novel agents like lefamulin and omadacycline. We further analyze vaccine development hurdles alongside the potential of mRNA-LNP platforms targeting conserved adhesin epitopes. Our findings indicate that the lag between mechanistic insight and clinical implementation remains the most pressing challenge. Future research must shift from simple mechanistic elucidation to addressing real-world clinical dilemmas, including distinguishing colonization from infection through integrated pathogen-host evaluation, exploring synergistic use of antibiotics and immunomodulators targeting the IL-17 A pathway, advancing vaccine design that circumvents IL-17 A-mediated immunopathology via conserved epitope selection and mucosal delivery, and establishing real-time surveillance networks integrating genomics and clinical phenotypes. Collectively, this work provides a practical roadmap spanning molecular pathology to clinical practice for the precise management of M. pneumoniae infections.

This scoping review aimed to map the evidence on antibiotic-loaded microparticles developed as controlled-release systems for topical wound treatment. The review followed the JBI methodology and was reported in accordance with the PRISMA-ScR checklist. The most frequently investigated antibiotics were gentamicin (n = 4; 21.1%), ciprofloxacin (n = 3; 15.8%), and doxycycline (n = 3; 15.8%), followed by vancomycin, mupirocin, and rifamycin (n = 2; 10.5% each). Chitosan and gelatin were the most common matrices (n = 6; 31.6 % each), followed by alginate (n = 3; 15.8%). Most systems were incorporated into wound dressings, scaffolds, hydrogels, patches, or used as powder. Excisional wounds were the most frequently evaluated model (n = 12; 63.2%), followed by infected wounds (n = 5; 26.3%), whereas burn and diabetic wound models were less investigated (n=1, 5.3%). These findings suggest that antibiotic-loaded microparticles may act as multifunctional wound-care systems by combining infection control, controlled local antibiotic release, and support for wound healing.

Macrophages are of interest as candidates for adoptive cell therapy for solid tumors because they can infiltrate tumor tissue, engage target cells and influence the tumor microenvironment. However, macrophage products derived from primary monocytes remain difficult to standardize, expand and genetically modify. Pluripotent stem cell-derived myeloid cell lines (PSC-MLs) provide a renewable and engineerable myeloid platform, but their use as direct tumor-targeting effectors has remained incompletely defined. In this study, we generated macrophage-like cells from PSC-MLs carrying a doxycycline (DOX)-inducible anti-HER2 chimeric antigen receptor (CAR) and evaluated three separable features of the platform: in vitro tumor-cell control, contact-associated and CAR-modified transcriptional responses and postadministration persistence in vivo. Cells established from 2 human PSC backgrounds retained macrophage-associated phenotypes after differentiation. In coculture with HER2-expressing tumor cells, the cells showed measurable antitumor activity relative to untreated controls. The DOX-treated condition was compatible with a CAR-associated contribution in some comparisons, but uniform CAR-dependent enhancement was not established across tumor models. Live imaging documented phagocytic events but did not quantify their frequency. Transcriptomic profiling associated tumor-cell contact with inflammatory, trafficking and uptake-related programs, and the CAR-induced coculture condition with a relative emphasis on vesicular, lysosomal and proteostasis-related modules. In a subcutaneous coimplantation assay, in which tumor and effector cells were introduced together, treated groups showed short-term tumor-control signals relative to untreated controls at later observation points. However, an incremental benefit of the CAR-induced (DOX) condition was not clearly resolved. Luciferase-based tracking of ML-MPs showed marked loss by day 3 and no detectable signal by day 7. Repeated dosing was feasible, but its incremental benefit over single dosing could not be established in the small exploratory experiment.

Anorectal lymphogranuloma venereum (LGV) can mimic rectal malignancy, but diagnosis may be challenging when LGV-specific serovar testing is unavailable. A 26-year-old man who has sex with men presented with hematochezia and increased bowel movement frequency. Colonoscopy revealed a large deep rectal ulcer with mucopurulent exudate, and pelvic magnetic resonance imaging showed rectal wall thickening with regional lymphadenopathy, raising concern for rectal cancer. Histopathology showed inflammatory changes without malignancy. Rectal secretion testing was positive for Chlamydia trachomatis RNA, and the patient was clinically diagnosed with probable anorectal LGV. Oral doxycycline 100 mg twice daily for 21 days led to marked ulcer regression at 3 weeks and near-complete mucosal healing by 6 weeks. This case highlights the importance of considering sexually transmitted proctitis in young men who have sex with men patients with atypical rectal ulcers.

Complete responses in metastatic pancreatic adenosquamous carcinoma (ASCP) are extremely rare and carbohydrate antigen 19-9 (CA 19-9) interpretation is difficult during cholestasis. A 65-year-old man underwent Whipple procedure on 29 May 2025; pathology confirmed ASCP (pT3 pN2, R0). Contrast-enhanced magnetic resonance imaging (MRI) on 26 June 2025 showed 11 liver lesions interpreted as metastases. Treatment with folinic acid, fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) began on 7 July 2025. From cycle 2, high-dose intravenous vitamin C, doxycycline and later azithromycin were added by the patient and author as off-label home measures, without efficacy claims. After three cycles, follow-up MRI showed complete radiological regression of the hepatic lesions; MRI around the sixth cycle confirmed complete radiological response. Chemotherapy stopped after six cycles. In late September 2025, cholestasis and CA 19-9 rise were initially suspected as recurrence; after ursodeoxycholic acid, CA 19-9 decreased and normalized by 10 January 2026. Follow-up MRI on 20 February 2026 showed no visible hepatic lesions.

Lyme disease may involve the heart during early dissemination and most commonly produces atrioventricular (AV) conduction abnormalities. PR interval prolongation, therefore, frequently guides clinical suspicion and management. We describe a previously healthy man who presented with seizure-like activity, aborted cardiac arrest, transient atrial fibrillation, and cardiac magnetic resonance findings consistent with acute myocarditis, although AV conduction remained normal. Serologic testing subsequently confirmed Lyme carditis. The patient recovered completely with oral doxycycline. This case illustrates that electrical instability may occur despite preserved PR intervals and reinforces the need for suspicion in patients with compatible systemic features.

Black soldier fly larvae (BSFL) bioconversion of doxycycline-contaminated hen manure raises concerns about antibiotic resistance gene (ARG) transmission. Although core microbiota in gut may participate in ARG dynamics, the relative contributions of microbiota from manure and baseline larval gut to the BSFL gut resistome remain unclear. Using metagenomics, amplicon sequencing, and cultivable bacteria analysis, we found that: (1) Providencia, Klebsiella, Enterococcus, and Escherichia-Shigella dominated the BSFL gut and served as primary ARG hosts; (2) Fecal filtrate intervention drastically altered gut microbiota and ARG profiles, suppressing Klebsiella (by 95.56%) and Escherichia-Shigella (to < 0.5%) while enriching Providencia (3.53 fold increase) and Enterococcus, with increased ARGs such as tet(59) and qnrD1. Long-read metagenomic analysis indicated that viable manure-borne bacteria, rather than cell-free fecal filtrate, delivered structurally intact ARG-MGE units as key carrier of mobile resistance cassettes; (3) Source tracking (FEAST) assigned the majority of ARBs (> 90%) and their ARGs in the BSFL gut to the baseline BSFL gut source, with manure-derived ARBs contributing 4.80%. Culture-based 16S rRNA gene homology provided evidence consistent with possible manure-to-gut transfer of selected Escherichia-Shigella and Enterococcus. The BSFL gut resistome was more strongly associated with the baseline BSFL microbiota than with manure, but manure still represented a detectable source of ARB and ARG introduction. FEAST source assignments should be interpreted as composition-based bioinformatic estimates rather than definitive proof of origin, due to lack of direct functional tracing. These findings have critical implications for assessing the ecological safety of BSFL-based waste valorization.

Tristetraprolin (TTP/ZFP36) regulates mRNA expression; however, its target genes in lung cancer remain unclear. Using a CRISPR/Cas9-engineered doxycycline-inducible TTP knock-in model in H460 cells, we investigated the function of TTP in lung cancer cells. Induced TTP expression suppressed clonogenicity, spheroid growth, proliferation, invasion, and migration. Transcriptomic analyses integrated with public lung adenocarcinoma datasets identified glucosaminyl (N-acetyl) transferase 3 (GCNT3) as a key effector of TTP in cancer progression. Mechanistic analyses indicated direct TTP binding to GCNT3, reducing its expression. GCNT3 knockdown attenuated invasion and migration, and GCNT3 re-expression in TTP-induced cells restored and further enhanced these malignant behaviors, establishing a functional relationship between TTP and GCNT3. Transient TTP expression in H1299 cells also reduced GCNT3 levels. These findings identify GCNT3 as a direct TTP target that contributes to malignant behaviors in lung cancer cells, providing insights into post-transcriptional regulation of tumor progression.

Brazilian spotted fever, caused by Rickettsia rickettsii, is a life-threatening tick-borne disease endemic to southeastern Brazil and is associated with high mortality when treatment is delayed. Central nervous system involvement poses a particular diagnostic challenge because of nonspecific early symptoms and frequent misdiagnosis as dengue or leptospirosis. We report a case illustrating characteristic neuroimaging findings and therapeutic considerations in rickettsial encephalitis. We describe the clinical course, cerebrospinal fluid (CSF) findings, magnetic resonance imaging (MRI) findings, serologic results, and treatment response in a 23-year-old man who presented with febrile encephalopathy in an endemic region of Brazil. The patient had a five-day history of fever, erythematous macules, and progressive encephalopathy. CSF analysis showed elevated protein and lymphocytic pleocytosis. MRI showed T2/fluid-attenuated inversion recovery hyperintensities with restricted diffusion involving the bilateral corticospinal tracts and the splenium of the corpus callosum, forming a "boomerang" pattern. Clinical improvement followed initiation of empirical doxycycline and pulse methylprednisolone. Serologic testing supported the diagnosis of R. rickettsii infection with a positive immunoglobulin M titer of 1:512. Follow-up MRI showed near-complete lesion resolution at 4 months, with a residual splenial lesion persisting at 18 months. This case illustrates the importance of recognizing characteristic MRI patterns, including the "starry sky" and "boomerang" signs, as diagnostic clues in rickettsial encephalitis, even when the classic triad is incomplete. Early empirical doxycycline remains critical for neurologic outcomes, and adjunctive corticosteroids may have a role in selected cases when immune-mediated central nervous system injury is suspected.