Abstract Purpose An immune-mediated pathogenesis has been postulated for aplastic anemia (AA), and impaired Tregs and other immune abnormalities have been identified in patients with AA. However, the process by which abnormal immunity specifically damages hematopoietic stem cells (HSCs) remains unclear. We conducted primary clinical studies to investigate whether the depletion of HSCs in AA could be attributed to the collapse of immune privilege (IP) afforded by regulatory T cells (Tregs). Methods The distribution of Tregs in the bone marrow of children with AA, myelodysplastic syndrome (MDS), and control participants was separately detected by immunohistochemistry. T-helper 1 (Th1), T-helper 2 (Th2), and T-helper 17 (Th17) cells, cytokines, and HSCs in the bone marrow of the AA and control groups were examined using flow cytometry. Results Patients with AA showed significantly lower FoxP3 + /CD4 + ratios (AA vs. normal: 18.09% ± 5.38% vs. 21.72% ± 4.21%, P = 0.014; AA vs. MDS: 18.09% ± 5.38% vs. 22.63% ± 5.98%, P = 0.030) and reduced Treg counts (AA vs. normal: 4.07 ± 1.41 vs. 5.25 ± 1.86 cells/HP, P = 0.014; AA vs. MDS: 4.07 ± 1.41 vs. 5.30 ± 1.49 cells/HP, P = 0.024) near the endosteum. The bone marrow in patients with AA exhibited Th1 dominance (AA vs. normal: 39.80% ± 5.20% vs. 22.1% ± 2.9% in controls, P < 0.001) and Th2 reduction (AA vs. normal: 59.20% ± 5.30% vs. 77.20% ± 2.60%, P < 0.001), indicating IP dysfunction. Significant elevation of tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and interleukin (IL)-17 levels was observed in the bone marrow of patients with AA. Long-term (LT)-HSCs were severely depleted in patients with AA (AA vs. normal: 0.13% vs. 1.22%, P = 0.035), with moderate reduction in short-term (ST)-HSCs. Conclusions Patients with AA showed endosteal Treg reduction, Th1 dominance, elevated proinflammatory cytokine levels, and severe LT-HSC depletion, linking bone marrow IP dysfunction to HSC damage. These findings provide a mechanistic explanation for the specific loss of HSCs in AA and highlight the IP niche as a therapeutic target.

Importance:CD19-directed chimeric antigen receptor (CAR) T-cell therapy induces high remission rates in relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL), but relapse, which is often due to antigen loss, remains a major challenge. Dual-targeting CD19/CD22 CAR T-cell strategies may be associated with reduced antigen-negative relapse and improved remission durability. Objective:To evaluate the safety and efficacy of bicistronic CD19/CD22 CAR T-cell therapy in pediatric patients with relapsed or refractory B-ALL. Design, Setting, and Participants:This open-label, multicenter, phase 2 nonrandomized clinical trial enrolled pediatric patients with B-ALL at 5 major medical centers in China from January 2022 to August 2024, with a data cutoff of February 28, 2026. Median follow-up was 35.7 months (IQR, 29.8-41.0 months). Of 346 screened, 38 (11.0%) were excluded and 308 (89.0%) were eligible. A safety run-in established the recommended phase 2 dose, followed by cohorts with refractory disease, hematologic relapse, or isolated extramedullary relapse. Intervention:CD3-positive T cells were activated and transduced with a bicistronic lentiviral vector that encoded anti-CD19 and anti-CD22 CARs, then infused fresh after 5 to 7 days in culture. Lymphodepleting chemotherapy included fludarabine and cyclophosphamide. Consolidative transplant was reserved for patients with KMT2A- or ZNF384-rearranged acute lymphoblastic leukemia. Main Outcomes and Measures:Primary end points were safety, recommended phase 2 dose, event-free survival (EFS), and toxic effects of bicistronic CAR-T therapy in relapsed or refractory B-ALL, with or without transplant. Results:Among 261 patients (98 girls [37.6%]; mean [SD] age, 8.2 [3.8] years) with relapsed or refractory disease, 259 (99.2%) achieved complete remission with negative minimal residual disease. EFS was 70.9% (95% CI, 65.6%-76.7%) at 12 months, 63.2% (95% CI, 57.6%-69.4%) at 24 months, and 61.7% (95% CI, 55.9%-68.0%) at 36 months. Consolidative transplant was associated with improved EFS; the 24-month EFS was 57.9% (95% CI, 51.6%-65.0%) in patients without a transplant vs 85.7% (95% CI, 76.5%-96.1%) in patients with a transplant (P = .004). In 20 patients with isolated central nervous system relapse and 20 with testicular relapse, 24-month EFS was 60.0% (95% CI, 43.6%-82.6%) and 80.0% (95% CI, 64.3%-99.6%), respectively. Grade 3 to 4 cytokine release syndrome occurred in 129 patients (49.4%), and immune effector cell-associated neurotoxic effects occurred in 34 patients (13.0%). Conclusions and Relevance:In this nonrandomized clinical trial, bicistronic CD19/CD22 CAR T-cell therapy induced high rates of minimal residual disease-negative remission, with durable EFS in pediatric B-ALL. These findings support further evaluation in prospective trials. Trial Registration:Chinese Clinical Trial Register Identifier: ChiCTR2000032211.

Purpose:Triple-negative breast cancer (TNBC) is prone to relapse and metastasis due to the immunosuppressive state of the tumor microenvironment and limited exposure to relevant antigens, and chemotherapy alone has poor efficacy. We have developed a novel theranostic nanoplatform to address these problems: multifunctional nanocapsules (NCs) with a PD-L1-mediated gold shell induce immunogenic cell death (ICD) to remodel the immune microenvironment. PD-L1 and NLG919 dual immune checkpoints are programmed to synergistically sensitize photothermal therapy and chemotherapy, and photoacoustic imaging (PAI) is used to visualize and localize TNBC tissues for identification. Methods:DOX-NLG919@PLGA@Au-antiPD-L1 NCs (DNPA-aPD-L1 NCs) were prepared using an improved single emulsion water-in-oil (O/W) solvent evaporation method, electrostatic adsorption, gold seed surface-induced crystallization reduction method, and carbodiimide method. A series of animal models were established to focus on the in vivo PAI of NCs, the effects of photochemotherapy combined with immunotherapy and antitumor therapy, ICD induced by NCs, the metabolic distribution of NCs, and toxicity tests. Results:This project successfully constructed gold nanoshell-PLGA core NCs with PD-L1 antibody co-loaded with chemotherapeutic drugs doxorubicin and indoleamine 2,3-dioxygenase inhibitor NLG919. Laser-triggered release of DOX, NLG919, and photothermal therapy can synergistically induce immunogenic cell death (ICD), thereby enhancing tumor immunogenicity, inhibiting IDO, and reshaping the tumor immune microenvironment. This can effectively eliminate the primary TNBC lesions, inhibit recurrence and metastasis, significantly prolong the survival of tumor-bearing mice, and NCs have good in vivo biosafety. This diagnostic and therapeutic agent can be used for photochemotherapy, immunotherapy, and PAI to visualize and identify TNBC. Conclusion:The photochemotherapy mediated by the DNPA-aPD-L1 NCs we developed, combined with tumor microenvironment remodeling and immune activation, shows great promise for the diagnosis and treatment of TNBC.

Background:The clinical efficacy and prognostic factors of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) as a salvage approach for children with relapsed acute leukemia (AL) after a first allogeneic HSCT (allo-HSCT) remain unclear. This study aimed to evaluate the clinical efficacy, survival outcomes, and prognostic factors of second haploidentical HSCT in children with relapsed AL following prior allo-HSCT. Methods:This retrospective study included 40 pediatric patients (median age: 8.5 years) who underwent a second haplo-HSCT at two Chinese transplantation centers between January 2017 and December 2023. The primary endpoints were overall survival (OS) and leukemia-free survival (LFS); and secondary endpoints included cumulative relapse incidence and non-relapse mortality (NRM). Results:With a median follow-up of 16.0 months, 1- and 2-year OS rates were 77.8% and 65.5%, and LFS rates were 72.4% and 61.0%, respectively. The 2-year cumulative incidences of relapse and NRM were 26.6% and 15.1%, respectively. Multivariate analysis showed that B-cell acute lymphoblastic leukemia was associated with the most favorable 2-year OS (HR = 0.081, 95%CI: 0.007-0.877, P = 0.039). Grade III-IV acute GVHD occurred in 25.0% of patients, and chronic GVHD occurred in 50.0% (10.0% extensive). Conclusions:These findings suggest that second haplo-HSCT with myeloablative conditioning may be a viable and effective salvage option for pediatric patients with relapsed AL lacking matched donors, possibly through graft-versus-leukemia effects. Future studies should incorporate targeted therapies and immune modulation strategies to improve outcomes in this high-risk population.

ObjectiveThe present study aimed to analyze the efficacy and safety of letermovir for preventing cytomegalovirus (CMV) infection and its impact on immune reconstitution in children after allogeneic hematopoietic stem cell transplantation (allo-HSCT).MethodsThe retrospective analysis included 83 patients who underwent allo-HSCT at Shanghai Children’s Hospital between January 2022 and June 2025 and survived ≥100 days post-transplantation. Forty patients received letermovir as primary CMV prophylaxis (letermovir group), and 43 patients did not receive prophylaxis (control group). The primary outcomes were the post-transplantation incidence of CMV infection and CMV disease. Secondary outcomes included the effects of letermovir on acute graft-versus-host disease (aGVHD), hematopoietic reconstitution (time to neutrophil and platelet engraftment), liver function, incidences of Epstein-Barr virus (EBV) and BK virus (BKV) infections, and cellular immune reconstitution.ResultsThe cumulative incidence of CMV infection post-transplantation was significantly lower in the letermovir group than in the control group (100 days: 7.5% vs. 53.5%, p<0.001; 180 days: 12.5% vs. 53.5%, p<0.001). No CMV disease occurred in either group. CMV reactivation occurred in 3 patients (7.5%) after discontinuation of letermovir. In the letermovir group, CMV infection occurred later [mean (range): 90.7 (31–168) days vs. 42.7 (16–90) days, p=0.050], lasted for a shorter duration [11.8 (7–15) days vs. 17.5 (4–39) days, p=0.042], and had a lower mean viral load [3,175 copies/ml vs. 30,407 copies/ml, p=0.393]. No significant differences were observed between the two groups in the time to neutrophil and platelet engraftment, incidence of grade II–IV and III–IV aGVHD, incidence of liver function abnormalities, or rates of EBV/BKV infection. Multivariate analysis showed that letermovir prophylaxis was an independent protective factor against CMV infection within 100 days post-transplantation (hazard ratio: 0.127, p=0.001). At 90 days, 180 days, and 1 year post-transplantation, the T lymphocyte and B lymphocyte counts were significantly lower in the letermovir group than in the control group (p<0.05). By 1 year post-transplantation, there was no difference in NK cell counts between the two groups (p=0.094). Within the letermovir group, only CD8+ T cell counts were significantly increased 1 year post-transplantation compared to pre-transplantation (p=0.027).ConclusionLetermovir is safe and effective at reducing the risk of CMV infection in children after allo-HSCT, significantly delaying the onset of infection and shortening its duration. Although letermovir may impact early lymphocyte subset reconstitution, immune function can recover to pre-transplantation levels by 1 year post-transplantation.

Abstract Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. While genomic studies have identified key molecular subtypes and aberrations in ALL, it requires integrating multi-omics data to complete complex and time-consuming analyses in large retrospective cohorts. It is challenging to perform individualized clinical genomic analysis in real-world. We present a nationwide precision genomic study as part of the Chinese Children Cancer Group ALL 2020 clinical trial. Between 2020 and 2023, 6486 pediatric ALL patients were enrolled from 25 medical centers across 15 provinces in China. RNA-seq was performed for 5103 patients during diagnosis. We developed the National Children's Medical Center ALL Bio-Cloud (NCMC-ABC), an automated, cloud-based framework for real-time RNA-seq data process. NCMC-ABC is designed to analyze multiple clinically relevant genomic aberrations from single RNA-seq data, including molecular subtypes, coding and noncoding driver mutations, fusions and CNVs. The median turnaround time from sample collection to clinical reporting was 14 days across all hospitals, aligning with clinical treatment timelines. We established a molecular subtype classification framework for pediatric ALL, and successfully classified 94.94% of B-ALLs into 20 subtypes and 86.38% of T-ALLs into 11 subtypes. This framework significantly improved the traditional MICM approach, which classified only 48.58% of B-ALLs and did not account for T-ALL subtypes. The enhanced classification is due to the improved detection of key fusions (DUX4, PAX5, ZNF384, MEF2D rearrangements) and mutations (PAX5 P80R and IKZF1 N159Y). Meanwhile, we achieved more precise subtyping of HYPO, HYPER and KMT2A BALLs. The refined subtypes unveiled a distinct profile of Chinese B-ALL patients, with higher frequencies of HYPER, ETV6, DUX4 and PH subtypes, and lower frequencies of Ph-like, iAMP21 and HYPO, compared to Western cohorts. Importantly, the refined framework directly improved the risk stratification of patients. We identified a median of 2.44 pathogenic SNPs/indels and 1.28 fusions per patient. The driver mutations were detected in 259 genes in B-ALL and 156 in T-ALL. We observed different driver mutation profiles in our cohort compared to the Western cohort. Mutations in RAS pathway (NRAS, KRAS and PTPN11) were more frequent in Chinese patients, whereas the JAK-STAT (JAK2, IL7R, SH2B3 and CRLF2) pathway was more frequently mutated in Western cohort. We observed direct clinical relevance of these aberrations. For example, patients with TP53 and NR3C1 mutations showed inferior treatment response. The implementation of NCMC-ABC in a nationwide multicenter pediatric ALL clinical trial demonstrated its effectiveness and feasibility in real-world, improving risk stratification and therapeutic decision making in clinic. Citation Format: Han Wang, Jiaoyang Cai, Jie Yu, Shaoyan Hu, Yongjun Fang, Ju Gao, Jian Li, Hua Jiang, Xiuli Ju, Sixi Liu, Wenyong Kuang, Runming Jin, Liangchun Yang, Xuedong Wu, Xiaowen Zhai, Qun Hu, Hui Jiang, Ningling Wang, Chi Kong Li, Lirong Sun, Jiao Jin, Chun Li, Changda Liang, Yan Dai, Kaili Pan, Hao Xiong, Ching-Hon Pui, Shuhong Shen, Yu Liu. Cloud-based computational framework for individualized genomic analysis in pediatric acute lymphoblastic leukemia: A nationwide multi-center real-world clinical study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 5283.

Primary immune thrombocytopenia (ITP) is the most common acquired bleeding disorder in children, and management is challenging when first-line therapy fails. Hetrombopag is an oral thrombopoietin receptor agonist (TPO-RA). This phase 3 randomized, double-blind, placebo-controlled trial evaluated its efficacy and safety in children and adolescents with ITP who had an inadequate response or relapse after prior treatment. Children and adolescents aged 6–17 years were randomized 2:1 to receive once-daily hetrombopag (initial dose 2.5 mg) or placebo for 12 weeks, followed by a 12-week open-label hetrombopag extension. The primary endpoint was the proportion of patients with a platelet count ≥50 × 10⁹/L at Week 10. The key secondary endpoint was the proportion of patients with a sustained platelet response, defined as a platelet count ≥50 × 10⁹/L maintained for ≥6 weeks without rescue therapy between Weeks 5 and 12. Eighty-eight patients were randomized (hetrombopag, n=57; placebo, n=31). At Week 10, 61.4

IntroductionPediatric aplastic anemia (AA), a rare and potentially fatal disease, demonstrates significant heterogeneity in pathogenesis, disease severity, therapeutic regimens, and clinical outcomes.MethodsIn this study, clinical features and outcomes of 70 children with AA, including severe AA (SAA, n = 30), very severe AA (vSAA, n = 21) and nonsevere AA (nSAA, n = 19), were retrospectively analyzed, with a median follow-up of 60.7 months (range, 0.4-136.5 months).ResultsPatients with nSAA were mainly treated with cyclosporine A, whereas SAA/vSAA patients primarily received allogeneic hematopoietic stem cell transplantation (HSCT) followed by standard immunosuppressive therapy (IST). Ultimate therapy regimens differed significantly between patients with SAA/vSAA and nSAA (p = 0.001). SAA/vSAA group exhibited a higher overall response rate at the 2-year follow-up (85.5% vs. 55.6%, p = 0.019). The 2-year overall survival (OS) and event-free survival (EFS) for the entire cohort were 97.1% and 48.5%, respectively. In patients with SAA/vSAA, HSCT was associated with higher and faster cumulative complete response (CR) rate (p < 0.0001) and superior EFS (p = 0.0297) compared with IST. Two IST-resistant patients were observed to achieved CR with eltrombopag (EPAG) salvage therapy.Discussionpediatric AA carries excellent OS but suboptimal EFS. HSCT tends to yield more favorable EFS compared with IST in SAA/vSAA patients, and EPAG may act as an effective salvage option for appropriately selected IST-resistant individuals. Further multicenter prospective research is warranted prior to implementing these findings in routine clinical practice.

Juvenile dermatomyositis (JDM), a pediatric subtype of idiopathic inflammatory myopathy, is a relatively rare rheumatic and immune system disease among children. Although paraneoplastic dermatomyositis (DM) has been documented in adult malignancies, its association with acute myeloid leukemia (AML) in pediatric populations remains exceptionally rare. We present a male patient diagnosed with JDM at age 6, characterized by Gottron’s papules and muscle weakness. Despite receiving sequential immunosuppressive therapies and biological agents, the disease followed a relapsing-remitting course over 9 years. At age 15, he developed persistent knee arthralgia accompanied by intermittent fever lasting 8 days. Hematologic evaluation revealed thrombocytopenia (platelet count: 76 ×109/L) and leukocytosis (white blood cell count: 36.46 ×109/L), prompting bone marrow aspiration confirmed AML diagnosis (French-American-British M2 subtype). Following induction chemotherapy and two consolidation cycles, allogeneic hematopoietic stem cell transplantation (HSCT) from a matched unrelated donor was successfully performed. Notably, both JDM symptoms and AML achieved sustained remission at 1-year follow-up post-HSCT. This case suggests that HSCT may represent a potential therapeutic approach for refractory autoimmune-hematologic malignancy overlap syndromes, though further studies are required to validate its efficacy.

Photobiomodulation therapy (PBMt) using red light is an emerging non-invasive treatment modality, increasingly applied for managing neck and shoulder muscle discomfort. This article conducts a pilot study which explores the therapeutic potential of a portable and wearable 660 nm LED PBMt device in chronic neck pain. The pilot study was conducted as a self-controlled volunteer study using a dedicated 660 nm LED PBMt device for the treatment of chronic neck pain. Participants received continuous PBMt for a duration of four weeks. Assessments of neck pain and functionality were conducted using the visual analog scale (VAS), neck disability index (NDI), neck pressure pain threshold, and neck mobility, both at the outset and at two-week intervals post-treatment initiation. Additionally, Pittsburgh Sleep quality index (PSQI) Questionnaire was used to evaluated participants’ sleep quality. After two weeks of PBMt device application, there was a significant reduction in neck pain, improvement in pressure pain threshold, and enhancement in sleep quality. Neck mobility showed improvement following four weeks of continuous use. No adverse symptoms were reported by any participants. The wearable 660 nm LED PBMt device showed potential in alleviating symptoms of chronic neck pain and improving neck function. As a non-invasive, efficient and self-administered treatment option, it provided rapid symptom relief for chronic neck pain sufferers and contributes to an overall enhancement in health quality. However, its relative effectiveness remains to be determined in future research.

Photobiomodulation (PBM) has gained attention as a kind of anti-pain or anti-inflammation therapy, yet its efficacy in mitigating the symptoms and underlying metabolic disturbances of primary dysmenorrhea remains underexplored. Here, 630 nm light reduced menstrual pain and prostaglandin F2a/prostaglandin E2 dysregulation, regulated oxidation and lipid peroxidation levels, and improved uterus damage in oxytocin-induced mice. Notably, pulsed wave (PW) treatment exhibited superior efficacy compared to continuous wave application. Hence, this research focused on the effects of 630 nm PW on oxytocin-induced mice by examining changes in the uterine transcriptome and plasma metabolome. Results from integrated analyses revealed significant modifications primarily in antioxidant and lipid metabolism pathways, alongside shifts in biomarkers related to arachidonic acid metabolism. Quantitative real-time PCR confirmed the downregulation of critical genes associated with oxidative stress and inflammation, as well as the suppression of uterine smooth muscle contractions and lipid overaccumulation. These findings support the potential of 630 nm PW PBM as a viable option for clinical interventions in dysmenorrhea management.

Background:Blinatumomab, a bispecific T-cell engager targeting CD3+ and CD19+, promotes T cell-mediated cytotoxicity against B-cell precursor acute lymphoblastic leukemia (B-ALL). While its efficacy is established in relapsed/refractory (R/R) disease, its role as preemptive therapy for minimal residual disease (MRD)-positive patients or those experiencing chemotherapy delays remains undefined. Predictors of treatment failure also require further investigation. Methods:In this multicenter retrospective study, 105 patients who received blinatumomab were enrolled. Of these, 30 had R/R ALL, 21 were in complete remission (CR) with MRD positivity (CR-MRDpos), and 54 experienced chemotherapy delays. Eight patients received blinatumomab directly as reinduction therapy and 22 patients received burden-reduction chemotherapy prior to blinatumomab. In total, 11 children were in R/R status and 40 were in CR-MRDpos before treatment. Patients were subsequently bridged to stem cell transplantation, chimeric antigen receptor T-cell therapy (CAR-T), or protocol continuation. Treatment response was analyzed across CR-MRDpos, R/R, and CR with MRD negativity (CR-MRDneg). Immune reconstitution profiles (T-cell subsets, cytokine dynamics), cytogenetic markers, and clinical outcomes were assessed to identify predictors of treatment resistance. Results:The CR rate was 81.8% in R/R and 82.5% in CR-MRDpos patients (P = 1.000). Of 74 courses with CR-MRDneg, 73 remained MRD-negative during treatment. Univariate analysis revealed poor cytogenetics (P = 0.0001), CD19+ B-cell loss (P = 0.046), and BCR-ABL1 positivity (P = 0.002) as predictors of poor response. Cox regression analysis identified high MRD (P = 0.014), BCR/ABL1 (P = 0.065), and poor cytogenetics (P = 0.025) as independent risk factors. Blinatumomab significantly increased CD3+ T cells [0.96 (0.03-3.79) to 1.13 (0.26-7.74) ×109/L, P = 0.016], along with CD4+ [0.35 (0.01-1.39) to 0.47 (0.07-2.94) ×109/L] and CD8+ T cells [0.41 (0.01-2.39) to 0.56 (0.07-6.07) ×109/L] (P = 0.005 and P = 0.006, respectively).The 1-year event-free survival for CR-MRDneg, CR-MRDpos, and R/R patients was 97.8% ± 2.2%, 86.7% ± 6.2%, and 73.3% ± 8.1%, respectively (P = 0.001), while overall survival was 97.8% ± 2.2%, 100%, and 93.3% ± 4.6% (P = 0.029). Conclusions:Blinatumomab effectively clears MRD as preemptive therapy and serves as a bridging strategy during chemotherapy delays in pediatric B-ALL, while maintaining high response rates in R/R cases.

Androgenetic alopecia (AGA) is a prevalent hair loss disorder and influenced by genetic, hormonal, and environmental factors. Minoxidil and finasteride have been widely used for treating AGA. However, the side effects associated with these drugs often lead to poor patient compliance. In contrast, photobiomodulation (PBM), due to its safety and non-invasiveness, holds promising prospects for use. Although the promoting effects of PBM on AGA have been reported, the mechanisms by which PBM affects dermal papilla cells (DPCs) remain largely unknown. Hence, this study explored the impacts of both continuous wave (CW) and pulsed wave (PW) PBM on DPCs, and revealed the underlying actions of light parameters in PBM. Orthogonal experiments were conducted to evaluate the effects of CW PBM on DPCs at varying irradiances and doses, indicating that irradiance was the crucial parameter, as well as cell viability and proliferation were maximized at 8 mW/cm2 and 8 J/cm2. For PW PBM, response surface methodology was employed to determine the influences of duty cycles, frequencies, and doses. The findings highlighted frequency as a primary factor, with the optimum cell viability observed at peak irradiance 10 mW/cm2, duty cycle 80 %, 500 Hz, and 8.8 J/cm2. Notably, PBM could enhance cell viability, proliferation, and migration in DPCs by activating the Wnt/beta-Catenin signaling and suppressing Transforming Growth Factor signaling, particularly when applied in pulsed mode. Overall, this study determined the key light parameters that influence PBM effectiveness, further identified the optimal light conditions, and preliminary revealed into the mechanisms of PBM in DPCs, highlighting that PW PBM may be a competitive therapeutic option for alleviating AGA in the future.

Lead exposure is of high prevalence, and over a billion people are chronically exposed to alarming level of lead. Human immune system is highly vulnerable to lead, but the underlying mechanism remains unknown. Using single-cell mass cytometry and mass spectrometry-based proteomics, we performed a panoramic survey of lead targets at both cellular and molecular levels in murine immune system upon chronic lead exposure. We produced a single-cell landscape of lead, thiol metabolism and lead-induced toxicity across all immune cell types. We found that immune cells with extreme thiol metabolism are the most sensitive upon chronic lead exposure. It shows that CD4 + T cells and neutrophils are the most sensitive to lead, which is due respectively to a molecular mechanism rooted in their characteristic thiol metabolic capacity. Meanwhile, we found that lead accumulation by RBC further inflicted secondary toxicity to RBC phagocytes in spleen, e.g. macrophages and neutrophils. Unlike CD4 + T cells, which can be rescued by supplementation with thiol chelator, lead toxicity in these phagocytes cannot be effectively mitigated by thiol chelators. Overall, it forms a multiscale panoramic lead-immune system interactome upon chronic lead exposure, which provides valuable information for proactive prevention, therapy formulation and public health evaluation. Graphical headlights

Blue light (400-500 nm) photobiomodulation (PBM), particularly utilizing light-emitting diodes (LEDs), has garnered extensive attention for its therapeutic efficacy across various conditions, including oncology. Nevertheless, its impact on osteosarcoma cells remain inadequately characterized. This study sought to investigate the tumor-suppressive properties and underlying molecular mechanisms of LED blue light PBM in human osteosarcoma cell lines HOS and MG63. The results indicated that blue light PBM effectively suppressed cell proliferation and triggered G2/M phase cell cycle arrest. Moreover, blue light PBM activated apoptosis and ferroptosis, characterized by significant changes in ferroptosis-associated proteins (HO-1, PTGS2, GPX4). Concurrently, ROS accumulation triggered oxidative stress, as demonstrated by increased MDA and LPO levels, well-established markers of ferroptosis. These findings underscore the promising potential of LED blue light PBM as an innovative, non-pharmacological therapeutic strategy for osteosarcoma, warranting further investigation for future clinical applications.

Photobiomodulation (PBM) therapy, utilizing light to regulate cellular processes, holds promise as a cancer treatment. We aimed to explore PBM's impact on two oral squamous cell carcinoma (OSCC) cell lines, Cal-27 and SCC-25, under varying blue light irradiation conditions. Cal-27 and SCC-25 cells were exposed to 457 nm blue light at varying irradiances (2.5–70 mW/cm2) and radiant exposure levels (3–84 J/cm2). Cell viability, reactive oxygen species levels, mitochondrial function, apoptosis, proliferation, and proteins related to proliferation and autophagy were quantified. 457 nm blue light significantly reduced OSCC cell viability, with efficacy increasing proportionally to radiant exposure. This effect resulted primarily from inhibited cell proliferation, as we observed no significant apoptosis or necrosis. Additionally, blue light elevated reactive oxygen species levels in OSCC cells while selectively decreasing mitochondrial membrane potential in SCC-25 cells, suggesting variable cell-type responses. Besides, autophagy levels were modulated by blue light exposure. The study demonstrates that 457 nm blue LED photobiomodulation therapy inhibits OSCC cell progression by promoting autophagy and inhibiting PI3K/AKT pathway-mediated cell proliferation. These insights provide a basis for exploring therapeutic applications of photobiomodulation in oral cancer treatment.

Despite increasing evidence suggesting that red light photobiomodulation (R-PBM) and leonurus play important roles in analgesic and anti-inflammatory processes, data on their combined effect on primary dysmenorrhea (PD) are scarce. In this study, we reported the pain assessment of red light at various modes combined with leonurus on the oxytocin-induced model of PD mice. The combined intervention of pulsed R-PBM and leonurus decreased pain responses and PGF2α/PGE2 levels, alleviated uterine swelling and inflammatory infiltration, enhanced antioxidant levels (T-AOC, GSH-PX, SOD), and reduced lipid peroxidation (MDA, LPO) in the uterus, with its synergistic effect surpassing either treatment alone or the combination of continuous wave R-PBM with leonurus. Transcriptomic analysis demonstrated significant changes in differentially expressed genes associated with calcium signaling (Cav1, Cacna1c, Kcnmb1, Cnn1, and Myh11) and inflammatory response (Ptgs2, Jun, Fos, IL1rn, and IL17b) in the combination group, with concurrent downregulation of MLCK, COX-2, p-JNK/JNK, and IL17b protein levels, and upregulation of IL1rn, suggesting that the combined intervention of pulsed R-PBM and leonurus may alleviate pain through disruption of calcium homeostasis and induction of ROS-mediated inflammatory responses. Metabolomics studies of plasma revealed significant changes in lipid metabolism after the combined intervention, consistent with the transcriptomic findings. Hence, pulsed R-PBM combined leonurus has the potential to be an effective therapeutic approach for PD, as well as an alternative option for painful and inflammatory diseases; however, further exploration of its underlying mechanism is still necessary.