Angiogenesis plays a significant role in the progression of idiopathic pulmonary fibrosis (IPF). The RNA-binding protein IGF2BP3 is associated with fibrosis and angiogenesis, but its role in IPF angiogenesis remain unclear. Additionally, Tianlongjie (TL) has been confirmed to inhibit IPF progression, but the role of IGF2BP3 in this process also needs to be elucidated. A bleomycin (BLM)-induced pulmonary fibrosis rat model was established via intratracheal instillation of BLM, and an angiogenesis cell model was constructed by treating HPMVECs with VEGF165. HE staining was used to detect lung tissue injury. Masson staining, HYP content measurement, Western blot, and Immunohistochemistry assessed to evaluate fibrosis and angiogenesis progression. EdU staining was employed to detect cell proliferation. RIP-qPCR and dual-luciferase reporter assays were performed to examine the interaction between IGF2BP3 and HIF-1α. IGF2BP3 was abnormally highly expressed in pulmonary fibrosis. IGF2BP3 knockdown reduced the expression of HYP, COL-I, COL-III, α-SMA, CD31, CD34, and VEGFA in pulmonary fibrosis rat lung tissues, increased E-cadherin expression, and inhibited pulmonary fibrosis progression and microvascular formation in rats. In vitro, IGF2BP3 knockdown suppressed cell proliferation, migration and vascular endothelial cell angiogenesis. Mechanistically, IGF2BP3 may promote HIF-1α stability through m[6]A modification, and HIF-1α overexpression attenuated the inhibitory effect of IGF2BP3 knockdown on angiogenesis. Furthermore, TL treatment was associated with reduced fibrosis and lower IGF2BP3/HIF-1α expression. In conclusion, IGF2BP3 can promote pulmonary fibrosis-related angiogenesis by stabilizing HIF-1α expression, and TL inhibits IGF2BP3 and HIF-1α expression, angiogenesis and fibrosis progression in pulmonary fibrosis rats.

Ankylosing spondylitis (AS) is an inflammatory disease marked by aberrant new bone formation and spinal ankylosis. Transforming growth factor-β1 (TGFβ1) is implicated in osteogenesis, yet its downstream effectors in AS remain unclear. Osteonectin, a glycoprotein secreted by osteoblasts, plays a critical role in bone formation with TGFβ1, but has not been studied in AS. This study aimed to investigate the TGFβ1-osteonectin mediated regulation of osteogenic activity in AS. Serum levels of TGFβ1, osteonectin, and osteocalcin were measured in AS patients and healthy controls. Measured these serum levels were compared with the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). Enthesis cells isolated from AS spinal tissues were stimulated with recombinant TGFβ1 in vitro. Proliferation, matrix production, migration, and clonogenicity were evaluated. Immunohistochemical staining of spinal tissues was performed to assess osteonectin expression. AS patients showed significantly elevated serum levels of TGFβ1 and osteonectin compared to healthy controls. Osteonectin expression, but not osteocalcin, was significantly correlated with serum level of TGFβ1. TGFβ1 stimulation enhanced proliferation, collagen deposition, migratory capacity, and colony formation in enthesis cells derived from AS patients. Immunohistochemistry revealed increase of osteonectin expression in periosteal regions of AS tissues. These findings suggest that osteonectin is a TGFβ1-responsive effector involved in early osteoprogenitor activation and may contribute to pathological bone formation in AS. Osteonectin represents a potential biomarker and therapeutic target for early structural progression in AS.

Pseudomonas aeruginosa produces the blue-green phenazine pigment known as pyocyanin, which has shown promise in the fields of health, agriculture, environmental protection, and cosmetics. Because of their natural colour, safety, and inexpensive manufacturing costs, microbial pigments are a promising substitute for natural pigments and offer a wide range of possible applications. The present work focused on the extraction of a blue-green pigment produced by Pseudomonas aeruginosa. The chloroform extraction method was employed to extract the pigment. The yield of total pigment production was 50 mg/ml. The extracted pigment was chemically characterized by UV-vis, HPLC, GC-MS, FTIR. The antifungal properties were assessed using agar well diffusion method and the results showed inhibition against four pathogens (Fusarium oxysporum (15.60 mm), Aspergillus niger (25.60 mm), Rhizoctonia solani (14.30 mm), Magnaporthe oryzae (28.00 mm) at 30 mg/ml concentration followed by 20 mg/ml. The evaluation of the biocolor as a dye was executed on different types of fabrics (velvet, wool, georgette, cotton silk) of 3 × 3 cm which was collected from the local market of Jammu. The dyed fabrics were checked for washing, rubbing, and light fastness and also checked the pigment absorption by fabrics. The antimicrobial properties of dyed fabrics were assessed using Bit diffusion method and the results showed inhibition against four human pathogens (Escherichia coli, Bacillus cereus, Klebsiella pneumonia and Staphylococcus aureus). The highest zone was shown against B. cereus of 15.60 mm (unmordant velvet fabric) and against S. aureus of 20.30 mm (mordant velvet fabric). The potential of bacterial pigments (bio pigments) as sustainable, non-toxic dyeing agents with broad applicability across textile and biomedical domains, offering a promising alternative to synthetic dyes.

Cyclophosphamide (CP) is an effective chemotherapeutic agent whose clinical use is limited by nephrotoxicity associated with oxidative stress and inflammation. This study investigated the potential nephroprotective effects of quercetin (QUE) and hesperidin (HSP) against CP-induced renal injury in rats. Thirty-six male Wistar albino rats were randomly assigned to six groups (n = 6): Control, QUE, HSP, CP, QUE + CP, and HSP + CP. QUE and HSP were administered orally at a dose of 100 mg/kg/day for 15 days. CP (200 mg/kg) was administered intraperitoneally on the final day to induce nephrotoxicity. Renal function was assessed using serum biochemical parameters (urea, uric acid, creatinine, blood urea nitrogen [BUN], albumin, and total protein), oxidative stress was evaluated by measuring renal antioxidant enzyme activities (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GPx], and glutathione S-transferase [GST]) together with malondialdehyde (MDA) levels, and histopathological alterations were examined using hematoxylin-eosin staining. CP administration significantly increased serum urea, uric acid, creatinine, blood urea nitrogen, and total protein levels (all p < 0.05). It also increased renal MDA levels (p < 0.001) while reducing SOD (p < 0.05), CAT (p < 0.05), GPx (p < 0.001), and GST (p < 0.001) activities, accompanied by marked histopathological damage characterized by glomerular degeneration, tubular injury, hemorrhage, and inflammatory cell infiltration. Pretreatment with QUE or HSP significantly attenuated these alterations (all p < 0.05). Both flavonoids improved renal biochemical parameters, restored antioxidant defense mechanisms, reduced MDA levels, and ameliorated histopathological alterations compared with the CP group. Although QUE showed numerically greater improvements across several outcomes, direct statistical superiority over HSP was not demonstrated. QUE and HSP exert protective effects against CP-induced nephrotoxicity by reducing oxidative damage and preserving renal tissue integrity. These findings suggest that flavonoid-based adjunctive interventions may represent a promising strategy for reducing chemotherapy-associated renal injury and warrant further mechanistic and translational investigation.

Odontogenic facial cellulitis is the most common facial space infection worldwide, originating from untreated dental caries and progressing to life-threatening complications. This stems from the polymicrobial nature of the disease, along with the widespread and over-the-counter misuse of antibiotics in Egypt. This study aims to identify the pathogenic bacterial species involved in odontogenic facial cellulitis in an Egyptian patient sample. Forty-four samples were collected from patients presenting with odontogenic facial cellulitis. Bacterial profiles were investigated using selective media, Gram staining/colony identification, biochemical tests, and Clinical and Laboratory Standards Institute standardized antibiotic susceptibility testing. Resistant strains (≥ 3 agents) were identified using 16 S rRNA sequencing and deposited in the NCBI GenBank. Odontogenic cellulitis originated primarily from lower posterior teeth, specifically the lower first molar, and spread commonly in the submandibular and submental spaces. Regarding bacterial profile, the Gram-positive cocci were the predominant ones. Complete resistance to metronidazole was reported, while previous antibiotic administration showed no statistically significant association with susceptibility to amoxicillin and clindamycin. Among multidrug-resistant isolates, 16 S rRNA sequencing identified predominantly Bacillus, Enterococcus, and Staphylococcus species. Two isolates showed < 90% identity to known species, suggesting possible novel taxa and informing empirical therapy through phenotypic resistance profiles.

Fixation of tissues and cells is an essential step in histological analysis; however, structural deformation and fluorescence signal attenuation caused by fixatives often pose challenges. This study aimed to evaluate the performance of a newly developed fixative, the FM Fix, by comparing it with conventional fixation methods in tissue staining, optical clearing, and flow cytometry analysis. FM Fix demonstrated staining properties comparable to those of standard fixatives and showed superiority with respect to tissue structure retention. Optical clearing allowed the visualization of fluorescent signals at greater depths. In flow cytometry using green fluorescent protein (GFP)-expressing cells, FM Fix minimized the loss of GFP fluorescence, preserved cell membrane integrity, and maintained cell size. Furthermore, the staining quality of human renal biopsy samples was equivalent to that of 10% neutral buffered formalin (NBF). These findings suggest that FM Fix has excellent structural preservation, fluorescence retention, and antigen preservation properties, making it broadly applicable for histological evaluation and quantitative cellular analysis.

Cisplatin (Cis), an index drug with the greatest gonadotoxic potential, affects both primordial follicles and developing follicles (pre-antral) in vivo. Mesenchymal stem cell-derived exosomes accelerate cell proliferation and wound healing. Exosomes have been shown to induce tissue regeneration by transferring growth factors, growth factor receptors, enzymes, cytokines, DNA, miRNA, mRNA, ncRNA, proteins, and lipids from cell to cell. In this study, in order to investigate the protective effects of exosomes obtained from umbilical cord-derived mesenchymal stem cells against premature ovarian failure caused by Cis, in addition to histopathological methods, it was aimed to investigate the expressions of apoptosis, inflammation, and cell proliferation immunohistochemically at the protein level. For this purpose, 50 Wistar albino adult female rats were divided into five equal groups: control group, exosome (Exo) group, Cis group, Exo + Cis group, and Cis + Exo group. At the end of the study, ovarian tissues were removed. TNF-α, IL-1β, and IL-6 enzyme levels were measured. AMH, HIF1-α, NF-κβ, IL-1β, PCNA, and VEGF proteins were evaluated by the immunohistochemistry staining method. When histomorphometric evaluations and AMH immunoreactivity results were examined, it was seen that Cis caused a decrease in the number of preantral follicles, and Exo tolerated this decrease in the Exo + Cis group. It was determined that the increase in NF-κβ immunoreactivity increased Cis' NF-κβ uptake, and Exo had an anti-apoptotic effect. As a result, it was determined that Cis had a degenerative effect on ovarian morphology and follicle number and structure, and Exo applied before Cis had a prophylactic effect.

Single-cell-level resolution tumor therapy represents an advanced strategy against glioblastoma but lacks suitable theranostic agents. Here, we developed a spatiotemporal-switchable, two-dimensional (2D), bismuthene-based second near-infrared window (NIR-II) nanozyme. In this platform, the bismuthene scaffold simultaneously directed the assembly of indocyanine green (ICG) into ordered J-aggregates and anchored monodispersed platinum (Pt) atoms. The resulting J-aggregates acted as an optical antenna with a long-wavelength absorption peak at 895 nanometers and high photobleaching resistance of 78.0%, enabling the identification of single tumor cells with a resolution of 44.3 micrometers at 1350 nanometers for precise glioma resection. Postoperatively, the spatiotemporal-switchable function was activated for therapeutic intervention, in which the photothermal effect amplified the original efficiency of the catalase-like activity of Pt atoms by threefold, driving a surge in intracellular oxygen to combat tumor hypoxia. Upon 808-nanometer irradiation, the induced oxygen release in the tumor microenvironment amplified ICG-mediated photodynamic therapy, and combined with bismuthene-mediated photothermal therapy, it effectively inhibited residual tumors. In an orthotopic glioma mouse model, this approach minimized recurrence and achieved increased survival without inducing neurological or motor deficits. This work provides an atomic-level and molecular-level design blueprint for NIR-II nanotheranostic agents, paving the way toward clinical translation of single-cell-level precision medicine for brain malignancies.

Conventional receptor-targeted fluorescent probes have shown promise in tumor imaging, yet achieving a high tumor-to-normal (T/N) tissue ratio in vivo remains challenging due to limited biomarker density on tumor cell membranes. Here, we present an in situ assembly strategy of bioorthogonal-functionalized chimeric artificial receptors (BCARs) that locally constructs BCARs on tumor surfaces, which amplify fluorescence signals and enable high-contrast imaging. Rapid, selective membrane engineering under physiological conditions increases effective receptor density, enhancing fluorophore binding and tumor visualization. Mechanistic studies reveal that BCARs exhibit exceptional membrane retention and spatial precision, sustaining signal amplification in heterogeneous tumor microenvironments. In air-pouch and orthotopic bladder cancer models, BCARs notably improve the T/N imaging ratio and tumor boundary delineation. Translational validation with surgical specimens from 14 patients with bladder cancer confirms clinical feasibility. This work establishes a versatile platform for on-site receptor reprogramming and signal amplification, offering a powerful tool for high-contrast tumor margin detection.

Achilles tendinitis (AT) has posed as an intractable clinical problem, for which there is currently a lack of satisfactory treatment approaches. Local drug delivery has proven to be effective for AT therapy, but suitable drugs and local/sustained drug delivery technique for superior therapeutic effects are still in urgent need. In this work, screw-thread needle acupuncture-mediated in situ delivery of tangeretin@β-cyclodextrin sulfated sodium salt (TAN@CDs) complexes was developed for AT therapy. Briefly, TAN was firstly encapsulated into the cavity of CDs with a TAN loading rate of 4.6%. Then, a trimethyl[3-(trimethoxysilyl)propyl]ammonium chloride-modified screw-thread needle (TMSTN) was immersed into the TAN@CDs solution to fasten the TAN@CDs complexes to the grooves of the TMSTN through electrostatic interaction. The biosafe concentration of TAN@CDs solution was controlled at 30 mg/mL through hemolysis assay, H&E staining, and blood biochemical analyses. TAN@CDs could release TAN in a sustained manner for over 8 h in a simulated Achilles tendon microenvironment. TAN delivery amount of single acupuncture (sequential clockwise/anticlockwise rotation) of the TAN@CDs/TMSTN was determined to be 1.28 μg, and an Achilles tendon defect model of rat was applied to evaluate its therapeutic effects against AT. Gross appearance observation of the Achilles tendon, H&E staining, Masson staining, and biomechanical testing proved that through periodic acupuncture of the TAN@CDs/TMSTN, AT could nearly be cured. The superior therapeutic outcomes of TAN@CDs/TMSTN‑mediated acupuncture against AT are likely attributable to the synergistic interplay between the acupuncture intervention and the in situ release of TAN. Immunohistochemical staining demonstrated that the released TAN molecules treat AT through downregulating inflammatory cytokines and upregulating tendon repair-related factors, therefore promoting collagen synthesis and tenogenic differentiation throughout healing. In sum, this work reported an efficient strategy for AT therapy.

Nucleus pulposus (NP) cell quiescence maintains intervertebral disc homeostasis, while mTORC1 regulates autophagy-lysosomal function and inflammatory secretion to preserve quiescence-rapamycin specifically targets mTORC1. Herein, we fabricated rapamycin-nanoliposomes (rapa-lipos) via ultrasonic dispersion, thin-film dispersion, and filtration to improve rapamycin bioavailability, investigating their role in inhibiting the senescence phenotype of NP cells through β-gal staining, lysosomal staining, transmission electron microscopy, ELISA, and cell cycle inhibitors. The mechanistic effects of rapa-lipos on mTORC1, NLRP3/Caspase-1 pathway (NCP) and autophagy-lysosomal pathway (ALP) were also analyzed by western blotting, immunofluorescence (IF), Si-RNA (raptor), and PCR. In vivo, rapa-lipos were injected into rat intervertebral disc with IL-1β-induced degeneration, assessed via HE staining, x-ray, MRI, and IF. Rapa-lipos exhibited high encapsulation efficiency, favorable drug loading, uniform particle size, and controlled release, suppressing NP cell senescence-related phenotypes (morphological changes, elevated IL-1β/TNF-α secretion, increased β-gal activity, lysosomal dysfunction, upregulated P21/P16 and reduced P27 expression). Mechanistically, rapa-lipos targeted-inhibited mTORC1, then blocked NCP and activated ALP to maintain NP cell quiescence. In vivo, x-ray, MRI and histological evaluation confirmed rapa-lipos mitigated intervertebral disc degeneration. Collectively, rapa-lipos target mTORC1-mediated NCP and ALP to inhibit NP cell senescence, offering a promising strategy for intervertebral disc degeneration prevention.

Objective: To evaluate the efficacy and safety of a novel silicone hydrogel multifocal soft contact lens for presbyopia correction, and to verify its non-inferiority compared with a conventional hydrogel multifocal contact lens. Methods: This was a prospective, randomized, open-label, parallel-group, multicenter non-inferiority clinical trial. From October 2024 to July 2025, 195 presbyopic subjects aged ≥40 years with near add power of +0.75 to +2.50 D were screened at 5 centers (Eye Hospital of Wenzhou Medical University, Eye & ENT Hospital of Fudan University, and Shenzhen Eye Hospital, Qingdao Eye Hospital of Shandong First Medical University, and Shanxi Eye Hospital Affiliated to Shanxi Medical University), and 180 were enrolled and randomized (computer-generated random number method) 1∶1 to the test group (samfilcon A silicone hydrogel multifocal soft contact lens, n=90) or the control group (polymacon hydrogel multifocal soft contact lens, n=90). Both type of lenses were monthly disposable for daily wear. Binocular corrected distance visual acuity (5 m) and near visual acuity (40 cm) were measured at each visit using a standard logarithmic visual acuity chart (5-point recording method). Subjective wearing experience was assessed by a validated acceptability questionnaire, and ocular surface status was evaluated via tear break-up time (TBUT) and corneal fluorescein staining. The primary endpoint was the wearing success rate at 1 week, defined as binocular corrected distance visual acuity ≥4.9 and near visual acuity ≥4.7. Missing values were imputed using the worst observation carried forward method. Rate differences and 95% confidence intervals (CI) were calculated by the Newcombe-Wilson method. Between-group comparisons were performed using Fisher exact test, independent-samples t test, or Wilcoxon rank-sum test. Sensitivity analysis was performed using the Cochran-Mantel-Haenszel method stratified by center. The non-inferiority margin was prespecified as -10%. Results: The full analysis set comprised 177 subjects (87 in the test group, 90 in the control group), with a mean age of (47.1±4.7) years, including 33 males and 144 females. After the data imputation, the wearing success rate at 1 week was 100.0% in both groups, with a rate difference of 0.00% (95%CI:-4.23% to 4.09%), meeting the non-inferiority criterion. Sensitivity analysis of raw data showed success rates of 96.6% and 96.7% in the test and control groups, respectively (adjusted rate difference -0.00%, P=0.991), consistent with the primary analysis. At all visits, binocular corrected visual acuities were within normal ranges in both groups, with no significant between-group differences (all P>0.05). Contact lens-corrected visual acuity was slightly lower than best spectacle-corrected visual acuity in both groups, with mean differences of approximately 0.03 to 0.06. The test group had a higher proportion of"excellent"subjective distance vision ratings at 1 week (50.0% vs. 36.8%, P=0.047), better comfort at 1 week and 1 month (both P<0.05), and better lens cleanliness at dispensing and 1 week (both P<0.05). Subjects with low add power had better total subjective scores at 1 week [2.0 (0.0, 4.0) vs. 4.0 (2.0, 5.0), P=0.004], with no significant difference at 3 months. At 1 month, the test group showed a smaller decrease in TBUT from baseline (P<0.05) and a higher proportion of grade 0 corneal fluorescein staining at 1 week and 1 month (both P<0.05); these differences disappeared by 3 months. No device-related serious adverse events occurred, and the incidence of adverse events did not differ significantly between groups. Conclusions: The novel silicone hydrogel multifocal soft contact lens is non-inferior to the conventional hydrogel lens in presbyopia correction, with a comparable safety profile and superior comfort, subjective experience, and short-term ocular surface protection. It can serve as an effective correction option for presbyopic populations.