Microneedles (MNs) have emerged as a promising platform for transdermal drug delivery, offering minimally invasive, programmable, and patient-friendly alternatives to conventional routes. Advances in fabrication and materials science have transformed MNs from simple metallic structures to multifunctional, biodegradable systems capable of dynamic drug release. This review analyzes MNs from the perspectives of structural design, material composition, and drug release kinetics. We examine key design parameters such as needle geometry and array configuration, and their effects on mechanical performance and delivery efficiency. MNs are categorized by type and functionality, highlighting innovations in tip design and backing layers for enhanced tissue penetration and payload control. A comparison of fabrication materials—including metals, inorganic nonmetals, natural and synthetic polymers—is presented, focusing on their degradation behavior and correlation with drug release timelines. Drug formulation strategies and pharmacokinetic models are also discussed, linking material–drug interactions to release profiles. Finally, recent applications in wound care, vaccination, hormone therapy, oncology, and ocular treatment are explored. This review bridges design, material, and pharmacokinetic considerations to support the development of next-generation MN systems with optimized spatiotemporal control for clinical applications.

We discuss recent advances in photo-responsive theranostic nanoplatforms for dental disease management and evaluate their mechanisms, performance and future design principles.

Bone remodeling and fracture repair require a transient inflammatory phase, yet how mechanical perturbation is converted into osteoclastogenic immune signaling remains unclear. Here, we identify a remodeling-associated CCR2+ macrophage subset that expands during force-induced alveolar bone remodeling and is reduced in fracture nonunion. Genetic ablation of CCR2+ macrophages using a dual-recombinase intersectional genetic strategy or myeloid Ccr2 deletion markedly attenuated osteoclastogenesis and bone resorption. Mechanistically, mechanical stimulation activated CCL2/CCR2 signaling, inducing PKC/CREB-dependent ATF3 activation and transcriptional upregulation of serum amyloid A3 (SAA3) in CCR2+ macrophages. SAA3 promoted osteoclast precursor differentiation through TLR4-dependent NF-κB signaling, whereas recombinant SAA3 partially rescued remodeling defects caused by ATF3 deficiency in CCR2+ macrophages. Collectively, these findings define a mechanotransduction-to-secretion pathway that links inflammatory chemokine signaling to osteoclastogenic bone remodeling.

RNA methylation has emerged as a critical frontier in epitranscriptomics, with 5-methylcytosine (m5C) drawing particular attention for its multilayered roles in post-transcriptional gene regulation. Recent studies demonstrate that m5C modulates diverse biological processes by stabilizing RNA transcripts, promoting nuclear export, shaping translational efficiency, and orchestrating noncoding RNA function. Analogous to DNA methylation, m5C is dynamically reversible and governed by a finely tuned regulatory system composed of “writers” (such as the NSUN family and DNMT2/TRDMT1), “readers” (including YBX1 and ALYREF), and “erasers” (TET enzymes and ALKBH1), which collectively dictate its spatial and temporal distribution. In lung cancer, disruption of this regulatory axis is increasingly recognized as a driver of tumor phenotypic remodeling, metabolic adaptation, and immune evasion. Notably, writer enzymes such as NSUN2, NSUN4, and NSUN6 promote malignant progression by stabilizing oncogenic transcripts, enhancing translation, and rewiring metabolic networks. Meanwhile, reader proteins YBX1 and ALYREF maintain the stability of m5C-modified RNAs and activate proliferative and pro-invasive signaling pathways, including PI3K/AKT, mTOR, and Hippo/Wnt. In addition, m5C plays a pivotal role in shaping the tumor immune microenvironment and modulating immune checkpoint activity, thereby influencing the responsiveness and resistance of lung cancer to radiotherapy, chemotherapy, targeted therapy, and immunotherapy.

analyze the morphometric and morphological variations of the temporomandibular joints (TMJs) using cone-beam computed tomography (CBCT) in individuals with and without temporomandibular disorders (TMD), and to explore their relationship with various sagittal and vertical skeletal malocclusion patterns. DICOM files of 432 TMJs from 216 patients (127 females, 89 males; mean ages 29.4 ± 12.6 and 31.2 ± 16.6 years, respectively) were analyzed using Dolphin Imaging software (version 11.95). Participants were grouped into two main groups: TMD (n = 199 TMJs) and control (n = 233 TMJs). Skeletal classification was based on the ANB angle to assess sagittal relationships, categorized as Class I (1°- 4°), Class II (> 4°), and Class III (< 1°). Vertical skeletal patterns were evaluated based on the SN-MP angle and classified as hypodivergent (< 27°), normodivergent (27°- 37°), and hyperdivergent (> 37°). There was no significant association observed between TMD and either gender or vertical skeletal pattern (P > .05). However, a significant relationship was found between TMD and sagittal malocclusion (P < .05). Patients in the TMD group demonstrated significantly greater anterior, lateral, and medial joint spaces (P < .05) and a more posterior condylar position. Furthermore, condylar morphology differed markedly between the TMD and control groups (P < .05). In the control group, round and oval condylar shapes were most common in the coronal and sagittal views, respectively. In contrast, the TMD group more frequently exhibited angled, finger-shaped condyles. TMJ morphological and morphometric alterations are significantly associated with TMD and may vary across different sagittal skeletal malocclusion patterns.

Purpose:The objective of this investigation was to examine the histopathological alterations in the rat hippocampus induced by myofascial trigger points (MTrPs), assess hippocampal neuronal excitability by measuring c-fos protein expression, and Non-targeted metabolomics was employed to profile hippocampal metabolite variations and elucidate the pathophysiological mechanisms underlying myofascial pain syndrome (MPS). Methods:Male SD rats were divided into MTrPs group (n=6) and control group (n=6). The MTrPs model was induced through localized blunt impact to the gastrocnemius muscle followed by repetitive eccentric exercise. Successful modeling was confirmed by the presence of palpable taut bands (TBs), along with measurements of mechanical and thermal withdrawal thresholds (MWT and TWL), and electromyographic (EMG) recordings. We assessed hippocampal neuropathological damage using HE and Nissl staining and measured c-fos protein expression to reflect hippocampal neuronal activity. Metabolomics analysis with statistical variable analysis helped distinguish affected individuals from controls. Results:TB detection, MWT, TWL and EMG confirmed successful model establishment. Pathological evaluation indicated a disorganized structure and neuronal injury in the CA1 region of the hippocampus in MTrPs rats, alongside elevated c-fos protein expression, suggesting heightened neuronal excitation and potential central sensitization. Metabolomic profiling revealed 79 differentially expressed metabolites (VIP > 1, P < 0.05) in MPS rats compared with controls. Further KEGG enrichment analysis demonstrated that 26 of these metabolites were involved in 20 metabolic pathways, with caffeine metabolism being notably affected (P = 0.000444), highlighting its critical role in the pathophysiology of MPS. Conclusion:MPS causes pathological damage to the hippocampus, and increased c-fos protein expression suggests possible central sensitization in MPS rats. Metabolomics analysis revealed significant hippocampal changes, particularly reduced caffeine metabolism, underscoring potential central mechanisms in MPS. This study enhances our understanding of MPS etiology based on hippocampal pathology and provides potential biological markers.

Malocclusion skeletal grading is a fundamental task in orthodontics, critical for diagnosis and treatment planning. Traditionally, cone-beam computed tomography (CBCT) is used for visual measurement, and the reconstructed lateral cephalograms are handed over to expert dentists for diagnosis. However, manual review is time-consuming, labor-intensive, and subject to inter-operator variability. Therefore, an automatic CBCT-based system is needed for reliable malocclusion skeletal grading. In this case, we develop TeethGNN, a novel graph-based framework designed to combine CBCT image features with morphological information for accurate and efficient malocclusion grading. TeethGNN utilizes a decoupled learnable decoder to directly predict key morphological indicators from CBCT images, eliminating the need for manual measurements. These morphological features are then fused with image features using a graph neural network (GNN), which effectively models the relationships between the modalities. To further enhance robustness and calibration, we introduce a collaborative calibration strategy. This strategy combines multi-scale graph adversarial perturbation for explicit calibration and nonlinear topological graph calibration for implicit confidence adjustment. Extensive experiments and ablation studies on our collected clinical dataset demonstrate that our malocclusion measurement system achieves 77.08% in accuracy and 89.61% in AUC, outperforming the compared state-of-the-art methods. These results validate the effectiveness of graph-based multimodal fusion and collaborative calibration in improving malocclusion grading performance. Our system shows strong potential for advancing computer-aided orthodontic diagnosis, providing an accurate and reliable solution for vision-based clinical measurement and diagnosis.

Alveolar bone defects, including dehiscence and fenestration, are commonly encountered in adult patients seeking orthodontic treatment. These anatomical deficiencies increase the risk of periodontal complications and may significantly compromise orthodontic tooth movement. Alveolar bone defects can also develop during orthodontic treatment, particularly in adult patients with narrow alveolar ridges requiring excessive tooth movement. Orthodontic-associated alveolar ridge augmentation (OARA) is an effective treatment approach that provides additional bone support and facilitates tooth movement, thereby reducing the incidence of periodontal complications and accelerating and broadening the scope of movement. At present, standardized diagnostic and treatment protocols for OARA in adult patients are lacking. This expert consensus aims to provide evidence-based recommendations for OARA in adult patients. A multidisciplinary panel of 27 experts conducted a Delphi-style process incorporating a targeted literature review and three voting rounds, achieving ≥70% agreement. Twenty-nine consensus statements across seven clinical domains, including pre-OARA examination, indications, bone graft material selection, timing, surgical protocols, standard operating procedures and considerations, were established with recommendations graded according to adapted GRADE criteria. This report presents a structured clinical framework for OARA and identifies future research priorities.

Reactive oxygen species (ROS)-based nanomedicine holds great promise for combating biofilm-associated infections (BAIs). Nonetheless, the strong antioxidant systems in these microenvironments lessen the effectiveness of ROS. The combination of ROS generation and depletion of antioxidant pathways is a potential approach to this issue. Herein, we present COF/HKUST-10, a composite platform of a copper-based metal-organic framework (HKUST-1) and pillararene-embedded covalent organic frameworks for BAIs. Both endogenous hydrogen sulfide and exogenous light activate this platform, thereby inducing synergistic catalytic reactions that enhance ROS generation and local antioxidant inhibition. Transcriptomic analysis revealed that ROS and Cu+/Cu2+ overload disrupted porphyrin metabolism in Porphyromonas gingivalis, severely impairing its energy metabolism and pathogenicity. This synergistic "three-in-one" antibacterial strategy involves ROS amplification, antioxidant system depletion, and copper ion-mediated bactericidal effects. The experiments demonstrated the material's exceptional efficacy, resulting in robust antibacterial activity, efficient biofilm eradication, and significant reduction in inflammation. This study presents a distinctive strategy to enable synergistic treatment of BAIs, broadening the practical applications of supramolecular materials in biomedical applications.

Background:Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide, and its underlying molecular mechanisms remain incompletely defined. N6-methyladenosine (m6A) RNA modification has emerged as a key epigenetic regulator of tumor metabolic reprogramming. However, the roles of the m6A writer methyltransferase-like 3 (METTL3) and the m6A reader insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) in NSCLC, particularly in lipid metabolic regulation, remain poorly characterized. The present study aimed to investigate the functional significance of METTL3 and IGF2BP1 in NSCLC, with particular focus on their regulation of FADS2 expression and lipid metabolism. Methods:Differentially expressed m6A-related genes were identified by analyzing RNA-seq data from The Cancer Genome Atlas (TCGA), followed by validation in 60 paired NSCLC and adjacent normal tissues. Gene and protein expression were examined by qRT-PCR and western blotting, respectively, with immunohistochemistry (IHC) further confirming protein levels in tissue specimens. Functional assays, including colony formation, Transwell migration/invasion, and Oil Red O staining, were performed in A549 and H1299 cells following METTL3, IGF2BP1, or FADS2 perturbation. The m6A modification on FADS2 mRNA was assessed by MeRIP-qPCR, and its association with METTL3 and IGF2BP1 was examined by RIP-qPCR. RNA stability was evaluated via actinomycin D chase assays, and rescue experiments were conducted through co-transfection of shRNA and overexpression constructs. The in vivo role of FADS2 was assessed using a xenograft tumor model. Results:METTL3 and IGF2BP1 were significantly upregulated in NSCLC tissues and were associated with poor overall survival. Silencing either gene inhibited NSCLC cell proliferation, migration, and invasion. FADS2 expression was markedly elevated in NSCLC and positively correlated with METTL3 and IGF2BP1 expression. Knockdown of FADS2 reduced lipid droplet accumulation and suppressed malignant phenotypes in vitro, while significantly inhibiting tumor growth in vivo. Mechanistically, m6A modification was enriched within the 3'-UTR of FADS2 mRNA, where both METTL3 and IGF2BP1 were found to bind. Loss of METTL3 or IGF2BP1 accelerated FADS2 mRNA decay, whereas their overexpression enhanced transcript stability. Rescue experiments further confirmed that METTL3 and IGF2BP1 cooperatively regulate FADS2 expression and thereby promote NSCLC progression. Conclusions:METTL3-mediated m6A modification of FADS2 transcripts is recognized by IGF2BP1, resulting in enhanced mRNA stability, increased lipid accumulation, and NSCLC progression. Our findings suggest that the METTL3/IGF2BP1-FADS2 axis contributes to lipid metabolic alterations in NSCLC and may serve as a potential therapeutic target.

Background:Silver needle thermotherapy (SNT) has a remarkable therapeutic effect on myofascial pain syndrome (MPS), but its mechanism of action remains to be clarified. This study aims to explore the effect of SNT on endoplasmic reticulum stress (ERS) in myofascial trigger points (MTrPs) of MPS rats and reveal its potential molecular mechanism. Methods:The MPS rat model was established. SNT treatment and TRPV1 adeno-associated virus injection were respectively performed on MTrPs of rats in different groups. After successful virus transfection, Hematoxylin-eosin staining, Transmission electron microscope, Western Blotting, Immunofluorescence analysis were performed. Experiments were conducted to observe the ERS of MTrPs and pain changes in each group of rats. Results:(1) The mechanical withdrawal threshold (MWT) of MPS rats decreased significantly, while SNT treatment could reverse the changes in MWT; (2) In MPS rats, MTrPs muscle fibers showed atrophy, degeneration and disordered arrangement. However, SNT treatment or interference with TRPV1 expression could improve the changes in muscle fibers; (3) SNT treatment or interference with TRPV1 expression can alleviate endoplasmic reticulum (ER) dilation and cystic space widening in MTrPs of MPS rats; (4) SNT treatment or interference with the expression of TRPV1 can inhibit the expressions of TRPV1, p-TRPV1, CaMKII, CHOP and BIP in the MTrPs muscle tissue of MPS rats. Conclusion:SNT can increase the pain threshold, repair the damaged myofascia, alleviate ERS and pain of MPS rats.

BACKGROUND:The strategy of limiting the availability of tumor cell phosphoglycerate dehydrogenase (PHGDH) has become a potential treatment for cancer. Modulation of the tumor-derived serine synthesis pathway to reprogram the tumor microenvironment represents a viable approach to optimize the efficacy of anti-tumor immunotherapy. However, currently no reliable PHGDH inhibitors of natural product origin have been approved for clinical use, and the precise pharmacological mechanisms underlying their biological activity have not yet been fully elucidated. PURPOSE:This study aims to identify PHGDH inhibitors from natural products and elucidate the underlying anti-tumor pharmacological mechanisms. METHODS:Multiple public databases were utilized to analyze the correlation between PHGDH and human non-small cell lung cancer (NSCLC) in this study. We took advantage of a natural compound library to perform the compound screening of PHGDH inhibitors. The binding capacity of DHT I to PHGDH was examined using molecular docking simulations, cellular thermal shift assay (CETSA), drug affinity responsive target stability (DARTS), and microscale thermophoresis (MST). Co-immunoprecipitation and western blotting assays were employed to investigate the regulatory effect of DHT I on PRMT1-mediated monomethylation of PHGDH. The roles of DHT I in PHGDH-mediated serine synthesis pathway in the lung cancer cells were determined through metabolomics analysis. Western blotting analysis was performed to examine the regulatory impact of DHT I on histone H3 lysine 4 methylation (H3K4me). Quantitative real-time PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) were utilized to determine the effects of DHT I on the transcriptional and secretory levels of IL-10 and TGF-β. Co-culture assays of tumor cells and bone marrow-derived macrophages (BMDMs) were performed to investigate DHT I-mediated polarization of macrophages. Single-cell RNA sequencing (scRNA-seq) analysis was performed to elucidate the molecular mechanisms underlying DHT I-mediated suppression of lung cancer progression in a murine model. Combined administration of DHT I and anti-PD-1 was employed to evaluate the therapeutic efficacy of this combinatorial regimen for anti-tumor immunotherapy. RESULTS:Elevated PHGDH expression and enzymatic activity were closely correlated with poor clinical prognosis in patients with NSCLC. DHT I was identified as a novel PHGDH inhibitor with therapeutic potential for NSCLC. DHT I bound to PHGDH at the Arg236 residue, which abrogated PRMT1-mediated methylation of PHGDH and consequently induced its functional inactivation. It also demonstrated that DHT I-mediated PHGDH inhibition reprograms the serine synthesis pathway in lung cancer cells, thereby reducing intracellular L‑serine and S-Adenosylmethionine (SAM) levels. DHT I downregulates H3K4me expression and suppresses the transcription of IL-10 and TGF-β, thereby modulating macrophage polarization in the tumor microenvironment. Furthermore, scRNA-seq analysis revealed that DHT-I-mediated reprogramming of tumor metabolism and alterations of the macrophage signature reversed the tumor immunosuppressive microenvironment, thereby potentiating the efficacy of anti-PD-1-based immunotherapy. CONCLUSION:Collectively, our findings demonstrate that DHT I is a potent PHGDH inhibitor with the potential for further optimization as a candidate agent for combination with immunotherapy to suppress the progression of NSCLC.

OBJECTIVE:This study analyzed mandibular third molar (M3M) impaction and its link to mandibular crowding. METHODS:This retrospective study included 351 M3M patients (Oct 2023-Oct 2024), with 320 analyzed after exclusion. Outcome measures included mandibular full dentition crowding (MFDC), retromolar space of the mandible (RSM), impaction angle of the mandibular third molar (IAM3M), crown width of the mandibular third molar (CW-M3), eruption height of the mandibular third molar (EH-M3), adjacent distance between the mandibular second and third molars (AD-M2M3), and root curvature of the mandibular third molar (RC-M3). Spearman correlation and linear regression identified risk factors for mandibular crowding. Receiver operating characteristic (ROC) analysis evaluated radiographic indicators' predictive value for severe crowding (>8 mm). RESULTS:Among 320 subjects, 487 impacted M3M were identified, 53.39% mesial, 20.12% horizontal, 16.22% vertical, 5.75% distal, and 4.52% buccal/lingual. Crowding severity was mild (34.38%), moderate (44.06%), and severe (21.56%). Severe crowding was most frequent in mesial (60.9%) and horizontal (26.1%) impactions, with other types below 10%. One-way ANOVA showed MFDC, IAM3M, CW-M3, and EH-M3 decreased, mesial > horizontal > distal > vertical > buccal/lingual (all P<0.05); RSM, AD-M2M3, and RC-M3 increased in the same sequence (all P<0.05). Spearman analysis revealed positive correlations between impaction type and MFDC (P<0.001). Linear regression identified mesial impaction, horizontal impaction, IAM3M>30°, and RSM<2.5 mm as independent risk factors for crowding (all P<0.05). IAM3M had the best predictive value for severe crowding (AUC=0.749, 95% CI: 0.703-0.795), followed by RSM (AUC=0.719, 95% CI: 0.665-0.773). CONCLUSION:M3M impaction worsens mandibular crowding, which offers clinical guidance.

Objective: Circular RNAs (circRNAs) affect fundamental biological processes, but their genetic effects on nonsyndromic cleft lip with or without cleft palate (NSCL/P) remain unclear. Methods: RNA sequencing of human embryonic palate mesenchyme cells identified circRNAs and their microRNA response elements (MREs) involved in NSCL/P. Genetic effects of single-nucleotide polymorphisms (SNPs) in MREs were evaluated in 858 NSCL/P cases and 1248 controls. Weighted genetic risk score (wGRS) and the predictive performance were evaluated through areas under the receiver operating characteristic curve (AUC). Results: We identified 6272 MREs of 574 known and 53 novel circRNAs harboring 130 SNPs. Rs629772 in circPRKCE and rs365132 in circUIMC1 showed significant associations with NSCL/P [rs629772: OR = 0.82, P = 6.45E-03; rs365132: OR = 0.78, P = 7.85E-04]. Adding these SNPs to wGRS improved AUC to 0.707 for NSCL/P prediction. Additionally, rs629772 T>C increased the binding affinity of hsa-miR-628-5p and circPRKCE, and rs365132 G>T increased the binding of hsa-miR-374c-3p and hsa-miR-3916 to circUIMC1, followed by the alteration of 9, 6, and 65 target genes for hsa-miR-628-5p, hsa-miR-374c-3p, and hsa-miR-3916, respectively, which participated in key biological pathways. Conclusion: This study indicated genetic effects in circRNA MREs associated with NSCL/P, offering insights into the genetic regulation and functional mechanisms of the disease.

The tumor microenvironment (TME) plays a pivotal role in cancer progression, though the molecular regulators governing its immunosuppressive properties remain incompletely characterized. In this study, we identify Makorin-2 (MKRN2) as a novel modulator of TME remodeling through integrated analyses of genetically engineered mouse models and human clinical data. Utilizing MKRN2 knockout mice, we observed significantly accelerated tumor growth compared to wild-type control, which was associated with profound alterations in immune cell composition, especially M2 macrophages. Specifically, MKRN2 deficiency promoted a phenotypic switch in tumor-associated macrophages (TAMs) from anti-tumor M1 to pro-tumorigenic M2 polarization, with quantitative analysis revealing a 3-fold increase in the M2:M1 ratio. Clinical correlation studies demonstrated that MKRN2 expression was frequently downregulated across multiple human malignancies, with low MKRN2 levels strongly correlating with advanced disease stage and reduced patient survival. Mechanistic investigations revealed a dual regulatory mechanism of MKRN2 downregulation: epigenetic silencing through promoter CpG methylation and post-transcriptional suppression by oncogenic miR-582-5p. At the molecular level, MKRN2 functioned as an E3 ubiquitin ligase that directly targeted NF-κB p65 for proteasomal degradation, thereby constraining NF-κB/COX2-mediated inflammatory signaling. Reconstitution experiments demonstrated that MKRN2 overexpression significantly inhibited tumor cell proliferation, migration/invasion and tumor growth. Our findings establish MKRN2 as a critical regulator of immunosuppressive TME formation through coordinated control of macrophage polarization and NF-κB/COX2 signaling, suggesting its potential as both a prognostic biomarker and therapeutic target for cancer immunotherapy.

OBJECTIVES:To identify risk factors for low back pain (LBP) recurrence and develop a clinically applicable predictive model, with emphasis on interactions between key factors. METHODS:A retrospective cohort study was conducted, including 216 patients with newly-diagnosed LBP as the derivation cohort (January 2023-June 2024) and 46 as the external validation cohort (July-December 2024). Independent risk factors were screened through univariate, least absolute shrinkage and selection operator (Lasso), and multivariate logistic regression. Interaction effects were evaluated. A nomogram was constructed and validated. RESULTS:The 1-month recurrence rate was 33.8%. Independent risk factors for recurrence included elevated white blood cell (WBC) count (OR=4.555, P<0.001), anxiety (OR=25.256, P<0.001), working >8 h/day (OR=8.748, P<0.001), and elevated interleukin-1β (IL-1β) (OR=3.356, P=0.008). Significant multiplicative interactions were observed between body mass index (BMI) and working hours, WBC and anxiety, and anxiety and working hours (all P<0.05). A positive additive interaction between WBC and anxiety was identified (RERI)=3.928). The nomogram demonstrated excellent discrimination (area under the receiver operating characteristic curve (AUC)=0.906 in the derivation cohort; 0.902 in the validation cohort), good calibration (Hosmer-Lemeshow P=0.06, 0.61), and optimal net benefit. CONCLUSION:Elevated WBC, IL-1β, anxiety, and prolonged working hours predict LBP recurrence, with notable interactions among these factors. The proposed nomogram aids personalized risk stratification and informs work-related and psychological interventions.

Background: Low back pain (LBP) is the leading cause of disability worldwide, severely impairing patients' quality of life, consuming substantial healthcare resources, and increasing medical costs while reducing productivity. Low back pain has become the leading cause of disability worldwide and a major global public health issue. Objective: To enhance the ability of diagnosis and treatment for LBP to meet the needs of clinical diagnosis and treatment. Main ideas: Based on high quality evidence based medical research on the diagnosis and treatment of LBP published domestically and internationally between January 2010 and December 2023, the expert group of the Pain Disease Diagnosis and Treatment Special Capacity Enhancement Project of the National Health Commission of China's Capacity Building and Continuing Education Centerhas formed recommendations for common treatment methods through rigorous argumentation and expert voting, to provide references for standardized diagnosis and treatment of LBP. This guideline adopts GRADE methodology to evaluate the level of evidence and strength of recommendation for the treatments of common chronic specific low back pain (cSLBP) and chronic non-specific low back pain (cNSLBP). Conclusion: LBP is characterized by high prevalence, significant disability rates, and frequent recurrence, imposing substantial burdens on individuals, families, and society. For patients, improving understanding of cLBP, practicing effective self-management, and actively cooperating with treatment are crucial for disease prognosis. Healthcare providers must enhance patient education and clinical competencies while strictly adhering to diagnostic and therapeutic guidelines for comprehensive cLBP management. Policymakers and academic organizations should focus on developing evidence-based clinical guidelines, strengthening healthcare system oversight, and promoting widespread implementation of standardized cLBP care protocols.

Teeth, like other ectodermal organs such as hair, skin, and sweat glands, are complex structures. Specifically, teeth are composed of four principal tissues: enamel, dentin, cementum, and pulp. Among these, dentin is a critical component, synthesized by odontoblasts-specialized cells derived from ectomesenchymal precursors originating in the neural crest. Odontoblasts are uniquely responsible for dentinogenesis, a process essential for tooth development and function. However, the molecular mechanisms regulating odontoblast differentiation remain poorly understood. In this study, we first analyzed a public single-cell RNA sequencing data set of postnatal (PN1) mouse molars and found Smpd3 as a potential gene of odontoblast differentiation. Then, we investigated the functional role of Smpd3 in odontoblast differentiation using a combination of histological, molecular, and bioinformatics approaches. Knockdown of Smpd3 expression via small interfering RNA (siRNA) significantly impaired odontoblast differentiation of mouse dental papilla cells (mDPCs), as evidenced by reductions in odontoblast-specific markers and mineralization. In contrast, overexpression of Smpd3 enhanced odontogenic differentiation and increased mineralized nodule formation of mDPCs. To elucidate the underlying molecular mechanisms, bulk RNA sequencing was conducted, revealing that Smpd3 is intricately linked to the Sonic Hedgehog (Shh) signaling pathway. In vitro studies and tooth germ culture were applied to validate the mechanism of Smpd3 on odontoblast differentiation through the Shh-Gli1 pathway. Mechanistically, we show that Smpd3 upregulates dentinogenic markers (Dspp, Dmp1) in a Shh-dependent manner. Smpd3 overexpression increased Shh pathway activity and promoted dentin formation ex vivo. This study highlights the critical role of Smpd3 in tooth development and provides novel insights into the molecular regulation of dentinogenesis, offering potential therapeutic targets for methods that promote dentin regeneration when natural repairs are compromised.

Aim or purpose: Contemporary root canal imaging modalities present ionizing radiation hazards while lacking capabilities for dynamic intraoperative visualization or sustained irradiation within abbreviated timeframes. Excessive radiographic exposure subjects healthcare practitioners to cumulative ionizing radiation risks, necessitating alternative imaging methodologies for localization and detection. Among various imaging techniques, near-infrared (NIR) imaging offers the distinction of real-time observation capability. Aqueous nanoclusters, as emerging nanomaterials, encounter significant limitations in practical NIR bioimaging applications: despite exhibiting superior biocompatibility relative to conventional NIR agents, their comparatively diminished photoluminescence intensity restricts their application spectrum. Consequently, the development of efficacious approaches to enhance NIR photoluminescence intensity in luminescent clusters constitutes a critical research imperative. Materials and methods: This study characterized Au NCs using the UV-visible spectrum, photoluminescence spectrum, excitation spectrum, and other techniques. Evaluate the safety, biocompatibility, and diagnostic potential of Au NCs using cytotoxicity, biocompatibility, and root canal imaging experiments. Results: Aqueous gold (Au) nanoclusters hold promise as imaging agents for root canal visualization. This study aimed to enhance NIR PL intensity and quantum yield of Au nanoclusters through trivalent cerium doping in Au clusters, achieving ∼7-fold photoluminescence enhancement and providing a novel strategy for improving NIR luminescence in aqueous systems. Conclusions: The Ce-modified Au clusters demonstrated effective root canal imaging capabilities in extracted teeth, establishing their potential as NIR imaging materials. This cluster modification approach enables in vitro root canal photoluminescence imaging and may serve as a novel clinical diagnostic probe in future applications.

Oral health is significant to a human’s overall quality of life. Phototheranostics, represented by photodynamic therapy (PDT) and photothermal therapy (PTT), has gained widespread application in oral disease treatment due to their high selectivity, non-invasiveness, cost-effectiveness, reduced side effects, and minimal drug resistance, but improvements in photosensitizers and photothermal agents are still needed to enhance their efficacy. The discovery of aggregation-induced emission (AIE) has ushered in a new direction for research on phototheranostics. Treatment of oral diseases can be considerably aided by AIE’s high luminescence yield, biocompatibility, photostability, and positive correlation. Based on the importance of phototheranostics as a promising tool in oral health care, this review focuses on recent advancements in AIE luminogens (AIEgens) across three domains: teeth whitening, oral infectious diseases, and oral cancer. We also delineate the challenges and future prospects in the field to expedite the clinical applications of AIEgens.