Objective To analyze the clinical outcomes of preoperative lift testing combined with levator palpebrae superioris complex (LPSC) surgery in patients with ocular myasthenia gravis (OMG) and ptosis. Design Retrospective study. Subjects, Participants, and/or Controls Twenty-six patients (41 eyes) with OMG-associated ptosis were included. No control group was involved. Methods, Intervention, or Testing Patients underwent preoperative lift testing followed by LPSC surgery. Clinical outcomes were evaluated by margin reflex distance 1 (MRD1), eyelid closure and blinking function, incidence of exposure keratitis, and pathological examination of levator muscle tissue, with postoperative follow-up of 6 months. Main Outcome Measures Changes in MRD1, surgical correction rate, eyelid function, incidence of exposure keratitis, and pathological findings. Results Preoperative lift testing predicted surgical tolerance, with 90.24% of patients passing the test. The MRD1 value significantly improved from −0.93 ± 1.55 mm preoperatively to 2.43 ± 0.42 mm at 6 months postoperatively (p < 0.001), with a complete correction rate of 90.2%. Active eyelid closure in the awake state was retained in 75% of operated eyes, complete blinking was achieved in 86.5%, and the incidence of exposure keratitis was 10%. Pathological examination revealed characteristic “sandwich-like” levator muscle fat infiltration in 56.25% of patients. Conclusion In patients with OMG and ptosis, an integrated strategy combining preoperative lift testing with LPSC surgery effectively and safely corrected severe ptosis. This approach achieved satisfactory functional and cosmetic outcomes while reducing the risk of postoperative exposure keratitis, providing a tailored surgical option for this high-risk patient population.

Corneal injury and nerve degeneration are complex issues associated with various eye diseases, presenting significant challenges in the field of ophthalmology. Current treatment methods often fail to completely restore corneal nerve function and tissue integrity after injury, underscoring the urgent need for new regenerative strategies. Neurotrophin-4 (NT-4), a member of the neurotrophin family, exerts crucial roles in cell survival and tissue repair through binding to the TrkB receptor. This study investigates the therapeutic potential of NT-4 for corneal injury. In vitro experiments demonstrated that NT-4 enhanced the migration of corneal epithelial cells and axonal outgrowth of trigeminal ganglion cells, effects that were abrogated by the TrkB-specific inhibitor ANA-12. In mouse models, compared to control groups, NT-4 accelerated the healing of both corneal abrasions and alkali burns, elevated corneal nerve density, restored corneal transparency. These findings suggest that NT-4 plays a pivotal role in corneal epithelial repair and sensory nerve regeneration through TrkB-mediated mechanisms, supporting its potential as a therapeutic agent for managing ocular surface injuries.

Ocular surface chemical injuries often result in permanent visual impairment and necessitate complex, long-term treatments. Immediate and extensive irrigation serves as the first-line intervention, followed by various therapeutic protocols applied throughout different stages of the condition. To optimize outcomes, conventional regimens increasingly incorporate biological agents and surgical techniques. In recent years, nanotechnology has made significant strides, revolutionizing the management of ocular surface chemical injuries by enabling sustained drug release, enhancing treatment efficacy, and minimizing side effects. This review provides a comprehensive analysis of the etiology, epidemiology, classification, and conventional therapies for ocular chemical burns, with a special focus on nanotechnology-based drug delivery systems in managing ocular surface chemical injuries. Twelve categories of nanocarrier platforms are examined, including liposomes, nanoemulsions, nanomicelles, nanowafers, nanostructured lipid carriers, nanoparticles, hydrogels, dendrimers, nanocomplexes, nanofibers, nanozymes, and nanocomposite materials, highlighting their advantages in targeted delivery, biocompatibility, and improved healing efficacy. Additionally, current challenges and limitations in the field are discussed and the future potential of nanotechnology in treating ocular diseases is explored. This review presents the most extensive examination of this topic to date, aiming to link recent advancements with broader therapeutic strategies.

To report a rare case of severe keratitis followed by SARS-CoV-2 infection after minimally invasive corneal neurotization (MICN) surgery for the first time. Retrospective single case report. A 59-year-old female presented to ophthalmology department of our hospital with facial paralysis induced by neurosurgeries. After detailed ophthalmological examination, she was diagnosed with Mackie stage III neurotrophic keratopathy (NK) in the right eye and subsequently underwent MICN and amniotic membrane transplantation. Postoperatively, corneal sensation and the epithelial defect showed gradual improvement, with corneal sensation recovering to 30 mm (measured by Cochet-Bonnet esthesiometer). However, thirteen months after MICN, she developed a corneal ulcer in the right eye one week after contracting SARS-CoV-2 (COVID-19). Supplementary investigations, including anterior segment photography, in vivo confocal microscopy (IVCM), and corneal scraping for pathogen detection, revealed recurrent corneal anesthesia and loss of corneal nerves, with no pathogens identified. After two weeks of empirical antiviral and antibacterial therapy yielded no significant improvement, a diagnosis of COVID-19-induced neurotrophic keratitis (Stage III Mackie) was established. Management consisted of prolonged medical therapy (including antiviral agents, antibiotics, nutritional supplementation, corticosteroids, and artificial tears), two amniotic membrane transplants, and one temporary tarsorrhaphy. Following two years of treatment and follow-up, the corneal lesion achieved complete healing with corneal nerve regeneration and restoration of corneal sensation. This study presents the first documented case of COVID-19-related NK following MICN established as a diagnosis of exclusion. This case underscores the critical need for comprehensive differential diagnosis to rule out infectious etiologies in post-MICN keratitis, ultimately leading to a diagnosis of exclusion for COVID-19-induced disease. The diagnostic approach outlined may offer valuable insights for similar presentations. After a protracted clinical course, the patient ultimately achieved restoration of corneal sensation and reinnervation, demonstrating the preserved regenerative potential of MICN-reconstructed neural pathways even after severe viral infection.

To analyze intraorbital Hydroxyapatite(HA) implant exposure occurring beyond ten years of implantation and suggest potential contributing factors. A retrospective cohort study based in the Shanghai Ninth People’s Hospital. One hundred and one Chinese patients with HA implant exposure were identified, from which 38 patients with implants exposure after ten years of insertion were selected and analyzed for demographic and medical records, clinical manifestations, surgery type, implant size, exposure area, follow-up duration, complications, details regarding prosthesis care, and treatment methods. All of the removed implants were sent for an HE pathologic examination. The 38 cases experienced exposure 10 to 19 years after implantation and presented to the clinic with increased secretions, proliferation of granulation tissue, visible suture exposure, and difficulty in wearing the external prosthesis. Other complications included implant forward position in 3 patients, eyelid retraction in 4 patients, and all the patients presented with post-enucleation socket syndrome. Reviewing the medical history, HA implant sizes ranged from 18 to 22 mm. Fourteen patients underwent implant repair surgery, of which 2 experienced recurrence, and ultimately, 26 implants were removed. Of the 26 removed implants, histologic examination showed that 17 exhibited chronic infection, and 12 had limited fibrovascular ingrowth. The questionnaires indicated that 26 patients did not renew the external prosthesis regularly. This study identified late complications and potential risk factors for implant exposure beyond ten years of implantation, including chronic infection, non-absorbable sutures, and low and delayed vascularization.

The use of dual-tracer contrast agents in clinical applications, such as sentinel lymph node (SLN) identification, offers significant advantages including enhanced accuracy, sensitivity, as well as comprehensive and multimodal visualization. In the current clinical practice, SLNs are typically marked prior to surgical resection by multiple and sequential injections of two tracers, the radioactive tracer and methylene blue (MB) dye. This imposes physical and psychological burden on patients and medical staff. Surface-enhanced Raman scattering (SERS) nanotags have emerged as promising SLN tracers due to their high sensitivity and specificity. In this study, we propose a novel single-injection composite tracer consisting of SERS nanotags and MB dye solution, to achieve the accurate intraoperative visualization and localization of SLNs. Laser excitation at the second near-infrared window (1064 nm) minimizes the MB fluorescence background interference, allowing the integration of SERS nanotags with MB solution to form the composite tracer, bridging two distinctive but complementary optical modalities. The feasibility of the composite tracer is demonstrated for SLN navigation on rabbit models. For the first time, we successfully visualize and localize multiple SLNs in the axilla of rhesus monkeys. Our study demonstrates the potential of combining MB with SERS nanotags for SLN navigation as the composite tracer, making a significant advancement toward the SLN biopsy in clinical applications.

Objective: To evaluate the surgical outcomes of a modified technique for treating congenital cilial entropion in children, which involves reducing tension step by step in the epicanthus and lower eyelid incision. Methods: The observational group consisted of 153 pediatric patients (81 males and 72 females ) who were treated using the modified technique, whereas the control group included 124 patients (68 males and 56 females ) who were treated using the rotating suture surgery. All the participants were bilateral. Surgical outcomes were classified as good, fair, or poor, and the recurrence rate, scar condition, inferior eyelid position, and patient satisfaction were also assessed. Results: The mean follow -up period was 9.13 +/- 3.50 months (range: 3-14 months ) for the observational group and 6.93 +/- 4.51 months (range: 3-14 months ) for the control group. In the observational group, surgical success with "good" outcomes was achieved in 300 eyes (98.04% ), compared to 224 eyes (90.32% ) in the control group. No recurrence occurred in the observational group, whereas the recurrence rate in the control group was 4.43%. Postoperative scar formation was mild in the observational group. The average scar score was 1.27 +/- 0.96 in the observational group and 2.70 +/- 0.99 in the control group, with a statistically significant difference (P < 0.001 ). Neither overcorrection nor postoperative ectropion was observed in both groups. Conclusion: The modified technique effectively corrected medial entropion and trichiasis in the lower eyelid, resulting in stable postoperative outcomes, mild scar formation, quick recovery, flexible eyelid motility, and stable ocular surface. Therefore, it can be widely applied to children with congenital entropion and trichiasis. (c) 2024 Published by Elsevier Ltd on behalf of British Association of Plastic, Reconstructive and Aesthetic Surgeons.

Surface-enhanced Raman spectroscopy (SERS) nanotags have garnered much attention as promising bioimaging contrast agent with ultrahigh sensitivity, but their clinical translation faces challenges including biological and laser safety. As breast sentinel lymph node (SLN) imaging agents, SERS nanotags used by local injection and only accumulation in SLNs, which were removed during surgery, greatly reduce biological safety concerns. But their clinical translation lacks pilot demonstration on large animals close to humans. The laser safety requires irradiance below the maximum permissible exposure threshold, which is currently not achievable in most SERS applications. Here we report the invention of the core-shell SERS nanotags with ultrahigh brightness (1 pM limit of detection) at the second near-infrared (NIR-II) window for SLN identification on pre-clinical animal models including rabbits and non-human primate. We for the first time realize the intraoperative SERS-guided SLN navigation under a clinically safe laser (1.73 J/cm2) and identify multiple axillary SLNs on a non-human primate. No evidence of biosafety issues was observed in systematic examinations of these nanotags. Our study unveils the potential of NIR-II SERS nanotags as appropriate SLN tracers, making significant advances toward the accurate positioning of lesions using the SERS-based tracer technique.

The field of second near-infrared (NIR-II) surface-enhanced Raman scattering (SERS) nanoprobes has made commendable progress in biomedicine. This article reviews recent advances and future development of NIR-II SERS nanoprobes. It introduces the fundamental principles of SERS nanoprobes and highlights key advances in the NIR-II window, including reduced tissue attenuation, deep penetration, maximized allowable exposure, and improved photostability. The discussion of future directions includes the refinement of nanoprobe substrates, emphasizing the tailoring of optical properties of metallic SERS-active nanoprobes, and exploring non-metallic alternatives. The intricacies of designing Raman reporters for the NIR-II resonance and the potential of these reporters to advance the field are also discussed. The integration of artificial intelligence (AI) into nanoprobe design represents a cutting-edge approach to overcome current challenges. This article also examines the emergence of deep Raman techniques for through-tissue SERS detection, toward NIR-II SERS tomography. It acknowledges instrumental advancements like improved charge-coupled device sensitivity and accelerated imaging speeds. The article concludes by addressing the critical aspects of biosafety, ease of functionalization, compatibility, and the path to clinical translation. With a comprehensive overview of current achievements and future prospects, this review aims to illuminate the path for NIR-II SERS nanoprobes to innovate diagnostic and therapeutic approaches in biomedicine. A schematic illustration delineating the current impacts and future directions of NIR-II surface-enhanced Raman scattering (SERS) probes in nanomedicine, encompassing the rational design of NIR-II SERS nanotags and addressing major challenges encountered in their biomedical applications. image

Timely blood reperfusion after myocardial infarction (MI) paradoxically triggers ischemia-reperfusion injury (I/RI), which currently has not been conquered by clinical treatments. Among innovative repair strategies for myocardial I/RI, microRNAs (miRNAs) are expected as genetic tools to rescue damaged myocardium. Our previous study identified that miR-30d can provide protection against myocardial apoptosis and fibrosis to alleviate myocardial injury. Although common methods such as liposomes and viral vectors have been used for miRNA transfection, their therapeutic efficiencies have struggled with inefficient in vivo delivery, susceptible inactivation, and immunogenicity. Here, we establish a nanoparticle-patch system for miR-30d delivery in a murine myocardial I/RI model, which contains ZIF-8 nanoparticles and a conductive microneedle patch. Loaded with miR-30d, ZIF-8 nanoparticles leveraging the proton sponge effect enable miR-30d to escape the endocytic pathway, thus avoiding premature degradation in lysosomes. Meanwhile, the conductive microneedle patch offers a distinct advantage by intramyocardial administration for localized, effective, and sustained miR-30d delivery, and it simultaneously releases Au nanoparticles to reconstruct electrical impulses within the infarcted myocardium. Consequently, the nanoparticle-patch system supports the consistent and robust expression of miR-30d in cardiomyocytes. Results from echocardiography and electrocardiogram (ECG) revealed improved heart functions and standard ECG wave patterns in myocardial I/RI mice after implantation of a nanoparticle-patch system for 3 and 6 weeks. In summary, our work incorporated conductive microneedle patch and miR-30d nanodelivery systems to synergistically transcend the limitations of common RNA transfection methods, thus mitigating myocardial I/RI.

Little is known about if and how circular RNAs (circRNAs) are involved in skeletal muscle atrophy. Here a conserved circular RNA Damage-specific DNA binding protein 1 (circDdb1), derived from the host gene encoding Damage-specific DNA binding protein 1 (DDB1), as a mechanism of muscle atrophy is identified. circDdb1 expression is markedly increased in a variety of muscle atrophy types in vivo and in vitro, and human aging muscle. Both in vivo and in vitro, ectopic expression of circDdb1 causes muscle atrophy. In contrast, multiple forms of muscle atrophy caused by dexamethasone, tumor necrosis factor-alpha (TNF-α), or angiotensin II (Ang II) in myotube cells, as well as by denervation, angiotensin II, and immobility in mice, are prevented by circDdb1 inhibition. Eukaryotic initiation factor 4A3 (EIF4A3) is identified as a regulator of circDdb1 expression in muscle atrophy, whereas circDdb1 encodes a novel protein, circDdb1-867aa. circDdb1-867aa binds with and increases the phosphorylation level of eukaryotic elongation factor 2 (eEF2) at Thr56 to reduce protein translation and promote muscle atrophy. In summary, these findings establish circDdb1 as a shared regulator of muscle atrophy across multiple diseases and a potential therapeutic target.

Background:Myopia, strabismus, and ptosis are common pediatric eye diseases, which have a negative impact on children and adolescents in terms of visual function, mental health, and health-related quality of life (HRQoL). Therefore, this study focused on those pediatric eye diseases by analyzing their risk factors and HRQoL for the comprehensive management of myopia, strabismus, and ptosis. Methods:A total of 363 participants (2-18 years old) were included in this study for risk factors analysis of myopia, strabismus, and ptosis. We collected demographic characteristics, lifestyle habits and eye care habits of these children and analyzed them by using univariable and multivariable logistic regression. In addition, we applied the Chinese version of Pediatric Quality of Life Inventory-Version 4.0 (PedsQL 4.0) to assess HRQoL in 256 children with strabismus and ptosis. Univariable and multivariable linear regression models were applied to evaluate potential influencing factors of HRQoL. Results:Of all the participants, 140 had myopia, 127 had strabismus, and 145 had ptosis. Based on the multivariable logistic regression analysis model, we found that the history of parental myopia and daily average near-distance eye usage time were risk factors for myopia, and increased body mass index (BMI) was identified as a risk factor for strabismus and ptosis. Individuals with ptosis possessed decreased HRQoL. The multivariable linear regression model suggested that daily average near-distance eye usage time, light intensity during visual tasks, and daily average sleep duration had potential influences on HRQoL. Conclusion:This is the first study to assess the risk factors and HRQoL of myopia, strabismus, and ptosis together. We identified risk factors for these common pediatric eye diseases to help doctors, parents, and teachers better manage them. Our study discovered that children with eye disorders exhibit a notably diminished HRQoL. Consequently, it emphasizes the necessity for increased social attention and mental health assistance for these children.

Lacrimal adenoid cystic carcinoma (LACC) is one of the most common malignant epithelial tumors of the lacrimal gland, characterized by high rates of local recurrence, distant metastases, and tumor-related mortality. This malignancy impairs the lacrimal gland's ability to secret tears, thereby disrupting the normal function of the ocular surface. Due to ineffective diagnostic approaches and the complex anatomical location of the lacrimal gland within the orbit, many LACC patients are often diagnosed at the later stages. Therefore, it is urgent to develop a simple and convenient method for early detection of LACC through biomarker analysis by liquid biopsies, such as blood or tears. Various microRNAs (miRNAs) derived from liquid biopsies have been shown to serve as biomarkers for early diagnosis of tumors. In the present study, we screened LACC-specific miRNAs using miRNA microarray analysis in both primary and recurrent patient groups. We then validate their expression by qPCR experiments conducted in tissues, cell lines, tear fluid and serum to explore the association between these miRNAs and LACC development and prognosis. Our findings reveal that hsa-miR-200b-3p, hsa-miR-200c-3p and hsa-miR-141-3p are significantly upregulated in LACC, and the microarray data showed that these three miRNAs were significantly elevated in the recurrence group compared to the primary group. In conclusion, detecting miRNA expression in tear fluid and serum provides non-invasive biomarkers for the early diagnosis of LACC and may facilitate monitoring outcomes related to lacrimal gland diseases.

Background Sufficient vascular network plays an important role in the repair of bone defects. Bone morphogenetic protein 2 (BMP2) being a key regulator of angiogenesis has attracted the attention of researchers. In addition, evidence has suggested that BMP2 coordinates with microRNAs (miRNAs) to form intracellular networks regulating mesenchymal stem cells (MSCs) angiogenesis. Elucidating the underlying mechanisms that are regulating adipose-derived mesenchymal stem cells (ADSCs) angiogenesis might provide more effective method to enhance bone regeneration. Methods We identified the specific miRNA in rat ADSCs during BMP2-induced angiogenesis and chose the most significant differentially expressed miRNA, miR-672. Three lentiviral system named Lenti-miR-672, Lenti-as-miR-672, and Lenti-miR-NC were transduced into the ADSCs individually. Then, the quantitative real-time polymerase chain reaction (qPCR), western blotting, and blood vessel formation analysis were performed to investigate the effects of miR-672 on ADSCs angiogenesis. Bioinformation platforms were used to screen the potential target of miR-672. Small interfering RNA (siRNA) against TIMP2 (si-TIMP2) mRNA were obtained from GenePharma, and then si-TIMP2 miRNA and miR-672 were co-transfected into ADSCs to detect the effects of TIMP2 on angiogenesis. Calcium phosphate cement (CPC) scaffolds that seeded the lentiviral-modified ADSCs were constructed to test the vascularized bone regeneration in vivo. Results Our data showed that after the angiogenesis of ADSCs induced by BMP2, miR-672 was the most significantly upregulated miRNA. Overexpression of miR-672 promoted the angiogenesis of ADSCs, while knockdown of miR-672 repressed the angiogenesis of ADSCs. The bioinformation prediction showed that TIMP2 might be the one of miR-672′ potential targets. TIMP2 protein expression was gradually decreased in ADSCs with overexpressed miR-672. And the angiogenic factors were upregulated in the ADSCs which were transduced with si-TIMP2. Then, the CPC scaffolds coupled the miR-672-modified ADSCs and showed the good potential in vascularized bone regeneration. The overexpressed miR-672 could greatly enhance the blood vessel volume and Microfil-labeled blood vessel numbers in newly formed bone. Conclusion BMP2 could promote the angiogenesis of ADSCs through stimulating the expression of miR-672 in ADSCs. miR-672 acted as a positive regulator on the angiogenesis of ADSCs, and incorporating the miR-672-modified ADSCs in the CPC could significantly promote the vascularization and the bone regeneration.

Combined immune checkpoint (ICP) inhibitors maximize immune response rates of patients compared to the single-drug treatment strategy in cancer immunotherapy, and prediction of such optimal combinations requires high-throughput imaging techniques and suitable data analysis. In this work, we report a rational strategy for predicting combined drugs of ICP inhibitors based on supermultiplexed surface-enhanced Raman scattering (SERS) imaging and correlation network analysis. To this end, we first built an ultrasensitive and super-multiplexed volume-active SERS (VASERS) nanoprobe platform, where Raman molecules are randomly arranged in 3D volumetric electromagnetic hotspots. By examining various bio-orthogonal Raman molecules with different electronic properties, we developed frequency modulation guidelines and achieved 32 resolvable colors in the Raman-silent region, the largest number of resolvable SERS colors demonstrated to date. We then demonstrated one-shot ten-color imaging of ICPs with high spectral resolution in clinical biopsies of breast cancer tissues, suggesting highly heterogeneous expression patterns of ICPs across tumor subtypes. Through correlation network analysis of these high-throughput Raman data, we investigated co-expression relationships among these ten-panel ICPs in cancer tissues and finally identified a variety of possible ICP combinations for synergistic immunotherapy of breast cancers, which may lead to novel therapeutical insights.

Purpose: To evaluate the corneal nerve regeneration after minimally invasive corneal neurotization (MICN) and to further clarify the recovery patterns of sensory and trophic functions of the corneal nerves. Design: A retrospective cohort study based in the Shanghai Ninth People’s Hospital. Methods: Eighteen patients (18 eyes) who underwent MICN for neurotrophic keratopathy due to intracranial surgery was conducted to analyze their follow-up data at 6, 12, 18, and 24 months after surgery. Results: At 12 months postoperatively, the growth of the central and peripheral corneal nerve fiber density (CNFD) was 11.47±8.56 and 14.73±8.08 n/mm 2 with subsequent improvement slowing down, and the patient’s corneal epithelium defect was healed ahead of the accomplishment of corneal nerve regeneration. The number of dendritic cells also reached its peak. At 18 months postoperatively, the recovery of central and peripheral corneal sensation was 37.22±23.06 mm and 39.38±18.08 mm with no subsequent improvement, and the growth of the central and peripheral corneal nerve branch density (CNBD) was 29.69±11.05 and 43.75±1.41 n/mm 2 , with a positive and significant correlation between corneal sensation and CNBD (at central r =0.632, P <0.005; at peripheral r =0.645, P <0.005). At 24 months postoperatively, mean CNFD, CNBD, and corneal sensation recovered significantly compared with preoperative, but a few patients’ corneal sensation recovered insignificantly with good CNFD recovery and poor CNBD recovery. Conclusions: After MICN, the trophic function of the corneal nerve recovers before the sensory function, and in particular, the recovery of sensation is based on the coexistence of the corneal nerve trunk and branches.

Introduction Blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES) is a rare genetic disease with diverse ocular malformations. This study aimed to investigate the disease-causing gene in members of a BPES pedigree presenting with the rare features of anisometropia, unilateral pathologic myopia (PM), and congenital cataracts. Methods The related BPES patients underwent a comprehensive ocular examination. Next, whole-exome sequencing (WES) was performed to screen for the disease-causing genetic variants. A step-wise variant filtering was performed to select candidate variants combined with the annotation of the variant's pathogenicity, which was assessed using several bioinformatic approaches. Co-segregation analysis and Sanger sequencing were then conducted to validate the candidate variant. Results The variant c.672_701dup in FOXL2 was identified to be the disease-causing variant in this rare BPES family. Combined with clinical manifestations, the two affected individuals were diagnosed with type II BPES. Conclusion This study uncovered the variant c.672_701dup in FOXL2 as a disease causal variant in a rare-presenting BPES family with anisometropia, unilateral pathogenic myopia, and/or congenital cataracts, thus expanding the phenotypic spectrum of FOXL2 .

Second near-infrared window (NIR-II, 1000-1700 nm) imaging is one of the foremost optical imaging techniques. However, surface-enhanced Raman scattering (SERS)-based research in this optical region remains in its infancy, mainly because of a lack of suitable NIR-II Raman reporters. Herein, we report the first example of a nickel dithiolene complex as a NIR-II resonance Raman reporter with intense long wavelength absorption (& epsilon; = 9.58 x 104 m-1 cm-1 at 1007 nm), fluorescence-free features and ultrahigh affinity to noble metal surfaces with its eight sulfur atoms. Surface-enhanced resonance Raman scattering nanoprobes constructed with such reporters enable high contrast and highly photostable lymph node imaging far superior to that possible with existing NIR-I and NIR-II SERS nanoprobes. The developed NIR-II nanoprobes allow deep optical penetration (8 mm) as well as in vivo SERS detection of deep-seated microtumors in mice.

Insufficient oxygen availability in tissue engineering is one of the major factors for the failure of clinical transplantation. One potential strategy to conquer this limitation is the fabrication of spontaneous and continuous oxygen supplying scaffolds for in situ tissue regeneration. In this work, a versatile fluorine-incorporating hydrogel is designed which can not only timely and continuously supply oxygen for mesenchymal stem cells (MSCs) to overcome deficient oxygen before vascularization in scaffolds, but can present a higher antibacterial capability to avoid bacterial infections. The HAp@PDA-F nanoparticles are first prepared and then incorporated with the quaternized and methacrylated chitosan forming CS/HAp@PDA-F by photo-crosslinking. In vitro results indicate that CS/HAp@PDA-F hydrogel has outstanding mechanical performance, moreover, it also has the oxygen-carrying ability to prolong survival ability, enhance proliferation activity, and preserve osteogenic differentiation potency and promote osteogenic-related genes expression of rat bone mesenchymal stem cells (rBMSCs) under hypoxic environment. Furthermore, the CS/HAp@PDA-F hydrogel can inhibit the growth of Staphylococcus aureus and Escherichia coli, providing a good antibacterial activity. Additionally, in vivo experiments demonstrate higher bone volume and bone mineral density, and more new bone tissue generation in CS/HAp@PDA-F group than in CS/HAp@PDA group. These results indicate that the rational design of fluorinated hydrogel possesses a good clinical application prospect for bone regeneration.