Apnea during moderate to deep sedation using continuous infusion of remimazolam compared to propofol and dexmedetomidine: A retrospective observational study.

Remimazolam's rapid onset and offset make it an innovative sedative for use during regional anesthesia. However, its respiratory safety profile is not well understood. We compared the continuous infusion of remimazolam with commonly used sedatives, propofol and dexmedetomidine, after regional anesthesia. In this retrospective study, the incidence of apnea (>10 seconds) was assessed in patients who underwent orthopedic surgery under regional anesthesia and received moderate to deep sedation using continuous infusion of remimazolam (group R: 0.1 mg/kg in 2 minutes followed by 0.5 mg/kg/hr). The incidence was compared with that of propofol (group P: 2-3 µg/mL target-controlled infusion) and dexmedetomidine (group D: 1 µg/kg in 10 minutes followed by 0.4-1 µg/kg/hr). Propensity score weighted multivariable logistic regression model was utilized to determine the effects of the sedative agents on the incidence of apnea. A total of 634 (191, 278, and 165 in group R, P, and D) cases were included in the final analysis. The incidence of apnea was 63.9%, 67.3%, and 48.5% in group R, P, and D, respectively. The adjusted odds ratios for apnea were 2.33 (95% CI, 1.50 to 3.61) and 2.50 (95% CI, 1.63 to 3.85) in group R and P, compared to group D. The incidence of apnea in patients receiving moderate to deep sedation using continuous infusion of remimazolam with dosage suggested in the current study was over 60%. Therefore, careful titration and respiratory monitoring is warranted.

AI-based betting anomaly detection system to ensure fairness in sports and prevent illegal gambling.

This study develops a solution to sports match-fixing using various machine-learning models to detect match-fixing anomalies, based on betting odds. We use five models to distinguish between normal and abnormal matches: logistic regression (LR), random forest (RF), support vector machine (SVM), the k-nearest neighbor (KNN) classification, and the ensemble model-a model optimized from the previous four. The models classify normal and abnormal matches by learning their patterns using sports betting odds data. The database was developed based on the world football league match betting data of 12 betting companies, which offered a vast collection of data on players, teams, game schedules, and league rankings for football matches. We develop an abnormal match detection model based on the data analysis results of each model, using the match result dividend data. We then use data from real-time matches and apply the five models to construct a system capable of detecting match-fixing in real time. The RF, KNN, and ensemble models recorded a high accuracy, over 92%, whereas the LR and SVM models were approximately 80% accurate. In comparison, previous studies have used a single model to examine football match betting odds data, with an accuracy of 70-80%.

Prevention of neointimal hyperplasia after coronary artery bypass graft via local delivery of sirolimus and rosuvastatin: network pharmacology and in vivo validation.

BACKGROUND: Coronary artery bypass graft (CABG) is generally used to treat complex coronary artery disease. Treatment success is affected by neointimal hyperplasia (NIH) of graft and anastomotic sites. Although sirolimus and rosuvastatin individually inhibit NIH progression, the efficacy of combination treatment remains unknown. METHODS: We identified cross-targets associated with CABG, sirolimus, and rosuvastatin by using databases including DisGeNET and GeneCards. GO and KEGG pathway enrichment analyses were conducted using R studio, and target proteins were mapped in PPI networks using Metascape and Cytoscape. For in vivo validation, we established a balloon-injured rabbit model by inducing NIH and applied a localized perivascular drug delivery device containing sirolimus and rosuvastatin. The outcomes were evaluated at 1, 2, and 4 weeks post-surgery. RESULTS: We identified 115 shared targets between sirolimus and CABG among databases, 23 between rosuvastatin and CABG, and 96 among all three. TNF, AKT1, and MMP9 were identified as shared targets. Network pharmacology predicted the stages of NIH progression and the corresponding signaling pathways linked to sirolimus (acute stage, IL6/STAT3 signaling) and rosuvastatin (chronic stage, Akt/MMP9 signaling). In vivo experiments demonstrated that the combination of sirolimus and rosuvastatin significantly suppressed NIH progression. This combination treatment also markedly decreased the expression of inflammation and Akt signaling pathway-related proteins, which was consistent with the predictions from network pharmacology analysis. CONCLUSIONS: Sirolimus and rosuvastatin inhibited pro-inflammatory cytokine production during the acute stage and regulated Akt/mTOR/NF-κB/STAT3 signaling in the chronic stage of NIH progression. These potential synergistic mechanisms may optimize treatment strategies to improve long-term patency after CABG.

Development of a Non-Contact Sensor System for Converting 2D Images into 3D Body Data: A Deep Learning Approach to Monitor Obesity and Body Shape in Individuals in Their 20s and 30s.

This study demonstrates how to generate a three-dimensional (3D) body model through a small number of images and derive body values similar to the actual values using generated 3D body data. In this study, a 3D body model that can be used for body type diagnosis was developed using two full-body pictures of the front and side taken with a mobile phone. For data training, 400 3D body datasets (male: 200, female: 200) provided by Size Korea were used, and four models, i.e., 3D recurrent reconstruction neural network, point cloud generative adversarial network, skinned multi-person linear model, and pixel-aligned impact function for high-resolution 3D human digitization, were used. The models proposed in this study were analyzed and compared. A total of 10 men and women were analyzed, and their corresponding 3D models were verified by comparing 3D body data derived from 2D image inputs with those obtained using a body scanner. The model was verified through the difference between 3D data derived from the 2D image and those derived using an actual body scanner. Unlike the 3D generation models that could not be used to derive the body values in this study, the proposed model was successfully used to derive various body values, indicating that this model can be implemented to identify various body types and monitor obesity in the future.

Perioperative Hypotension in Patients Undergoing Orthopedic Upper Extremity Surgery with Dexmedetomidine Sedation: A Retrospective Study.

(1) Background: limited data exist regarding the occurrence of hypotension associated with dexmedetomidine use and its risk factors in the context of intraoperative sedation for patients receiving peripheral nerve blocks. (2) Method: This single-center retrospective study assessed the incidence of hypotension in patients undergoing orthopedic upper extremity surgery with brachial plexus blockade. Patients were classified into three groups: group N (non-sedated), group M (midazolam), and group D (dexmedetomidine), based on their primary intraoperative sedative use. The primary outcome was the incidence of perioperative hypotension, defined as systolic blood pressure (SBP) < 90 mmHg or mean blood pressure (MBP) < 60 mmHg, at a minimum of two recorded time points during the intraoperative period and post-anesthesia care unit stay. Multivariable logistic models for the occurrence of hypotension were constructed for the entire cohort and group D. (3) Results: A total of 2152 cases (group N = 445, group M = 678, group D = 1029) were included in the analysis. The odds ratio for the occurrence of hypotension in group D was 5.68 (95% CI, 2.86 to 11.28) compared with group N. Concurrent use of a beta blocker, longer duration of surgery, and lower preoperative SBP and higher preoperative heart rate were identified as significant risk factors. (4) Conclusions: the increased risk of hypotension and the associated factors should be taken into account before using dexmedetomidine in these cases.

Effect of sequential release of sirolimus and rosuvastatin using silk fibroin microneedle to prevent intimal hyperplasia.

Intimal hyperplasia (IH) is a major cause of vascular restenosis after bypass surgery, which progresses as a series of processes from the acute to chronic stage in response to endothelial damage during bypass grafting. A strategic localized drug delivery system that reflects the pathophysiology of IH and minimizes systemic side effects is necessary. In this study, the sequential release of sirolimus, a mechanistic target of rapamycin (mTOR) inhibitor, and statin, an HMG-COA inhibitor, was realized as a silk fibroin-based microneedle device in vivo. The released sirolimus in the acute stage reduced neointima (NI) and vascular fibrosis through mTOR inhibition. Furthermore, rosuvastatin, which was continuously released from the acute to chronic stage, reduced vascular stiffness and apoptosis through the inactivation of Yes-associated protein (YAP). The sequential release of sirolimus and rosuvastatin confirmed the synergistic treatment effects on vascular inflammation, VSMC proliferation, and ECM degradation remodeling through the inhibition of transforming growth factor (TGF)-beta/NF-κB pathway. These results demonstrate the therapeutic effect on preventing restenosis with sufficient vascular elasticity and significantly reduced IH in response to endothelial damage. Therefore, this study suggests a promising strategy for treating coronary artery disease through localized drug delivery of customized drug combinations.

A FOXC2 inhibitor, MC-1-F2, as a therapeutic candidate for targeting EMT in castration-resistant prostate cancer.

Androgen deprivation therapy (ADT) is the major treatment option for advanced prostate cancer. However, prostate cancer can develop into androgen-independent castration-resistant prostate cancer (CRPC) which is resistant to ADT. An alternative treatment strategy for CRPC can be targeting the epithelial-mesenchymal transition (EMT). EMT is governed by a series of transcription factors of which forkhead box protein C2 (FOXC2) is a central mediator. Our previous research into the inhibition of FOXC2 in breast cancer cells lead to the discovery of MC-1-F2, the first direct inhibitor of FOXC2. In current study on CRPC, MC-1-F2 has shown a decrease in mesenchymal markers, inhibition of cancer stem cell (CSC) properties and decrease in invasive capabilities of CRPC cell lines. We have also demonstrated a synergistic effect between MC-1-F2 and docetaxel treatments, leading to a decrease in docetaxel dosage, suggesting the possible combination therapy of MC-1-F2 and docetaxel for the effective treatment of CRPC.

A Validation Study of a Deep Learning-Based Doping Drug Text Recognition System to Ensure Safe Drug Use among Athletes.

This study aimed to develop an English version of a doping drug-recognition system using deep learning-based optical character recognition (OCR) technology. A database of 336 banned substances was built based on the World Anti-Doping Agency's International Standard Prohibited List and the Korean Pharmaceutical Information Center's Drug Substance Information. For accuracy and validity analysis, 886 drug substance images, including 152 images of prescriptions and drug substance labels collected using data augmentation, were used. The developed hybrid system, based on the Tesseract OCR model, can be accessed by both a smartphone and website. A total of 5379 words were extracted, and the system showed character recognition errors regarding 91 words, showing high accuracy (98.3%). The system correctly classified all 624 images for acceptable substances, 218 images for banned substances, and incorrectly recognized 44 of the banned substances as acceptable. The validity analysis showed a high level of accuracy (0.95), sensitivity (1.00), and specificity (0.93), suggesting system validity. The system has the potential of allowing athletes who lack knowledge about doping to quickly and accurately check whether they are taking banned substances. It may also serve as an efficient option to support the development of a fair and healthy sports culture.

Comparison between costotransverse foramen block and thoracic paravertebral block for VATS pulmonary resection: A randomized noninferiority trial.

STUDY OBJECTIVE: The present study assessed whether costotransverse foramen block (CTFB) is noninferior to thoracic paravertebral block (TPVB) for postoperative analgesia in video-assisted thoracoscopic surgery (VATS) pulmonary resection. DESIGN: Single-center, double-blinded, randomized, non-inferiority trial. SETTING: Operating room and intensive care unit or ward in a tertiary hospital. PATIENTS: Patients aged 20 to 80 years with American Society of Anesthesiology physical status 1 to 3 scheduled for elective VATS pulmonary resection. INTERVENTIONS: Sixty patients were randomly allocated 1:1 to receive CTFB or TPVB using 15 mL aliquots of 0.5% ropivacaine at the T4-5 and T6-7 intercostal levels immediately after the induction of general anesthesia. MEASUREMENTS: The primary outcome was the area under the curve (AUC) of numeric rating scale (NRS, 0 to 10) during 24 h postoperatively (noninferiority limit was 24; NRS 1 per hour). The secondary outcomes included postoperative opioid consumption, rescue analgesic use, postoperative nausea and vomiting, pulmonary function, dermatomal spread of the blockade, and quality of recovery. MAIN RESULTS: Forty-seven patients were included for final analysis. The difference between the mean 24-h AUCs of NRS in the CTFB (34.25 ± 16.30, n = 24) and TPVB (39.52 ± 17.13, n = 23) groups was -5.27 (95% confidence interval [CI], -15.09 to 4.55), with the upper limit of 95% CI being far below the predefined noninferiority margin of 24. There was no significant difference in the dermatomal spread of the blockades between the groups, as both reached the upper and lower most levels of T3 and T7 (median). Additionally, there were no significant differences in other secondary outcomes between the two groups. CONCLUSIONS: The analgesic effect of CTFB was noninferior to that of TPVB during 24 h postoperatively in VATS pulmonary resection. Moreover, CTFB may offer potential safety benefits by keeping the tip of the needle far from the pleura and vascular structure.

Balloon Catheter-Integrated Piezoelectric Micropyramid Arrays for Measuring Vascular Stiffness.

Atherosclerosis is one of the severe cardiovascular diseases in which blood vessels lose elasticity and the lumen narrows. If atherosclerosis worsens, it commonly leads to acute coronary syndrome (ACS) due to the rupture of vulnerable plaque or aortic aneurysm. As the mechanical properties of vascular tissues vary from their conditions, measuring the vascular stiffness of an inner blood vessel wall may be applied to the accurate diagnosis of atherosclerotic symptoms. Therefore, early mechanical detection of vascular stiffness is highly needed for immediate medical attention for ACS. Even with conventional examination methods such as intravascular ultrasonography and optical coherence tomography, several limitations still remain that make it difficult to directly determine the mechanical properties of the vascular tissue. As piezoelectric materials convert mechanical energy to electricity without an external power source, a piezoelectric nanocomposite could be utilized as a balloon catheter-integrated mechanical sensor on its surface. Here, we present piezoelectric nanocomposite micropyramid balloon catheter (p-MPB) arrays for measuring vascular stiffness. We study the structural characterization and feasibility of p-MPB as endovascular sensors by conducting finite element method analyses. Also, multifaceted piezoelectric voltages are measured by compression/release tests, in vitro vascular phantom tests, and ex vivo porcine heart tests to confirm that the p-MPB sensor properly operates in blood vessels.

Sirolimus-Embedded Silk Microneedle Wrap to Prevent Neointimal Hyperplasia in Vein Graft Model.

We investigated the role of a sirolimus-embedded silk microneedle (MN) wrap as an external vascular device for drug delivery efficacy, inhibition of neointimal hyperplasia, and vascular remodeling. Using dogs, a vein graft model was developed to interpose the carotid or femoral artery with the jugular or femoral vein. The control group contained four dogs with only interposed grafts; the intervention group contained four dogs with vein grafts in which sirolimus-embedded silk-MN wraps were applied. After 12-weeks post-implantation, 15 vein grafts in each group were explanted and analyzed. Vein grafts applied with the rhodamine B-embedded silk-MN wrap showed far higher fluorescent signals than those without the wrap. The diameter of vein grafts in the intervention group decreased or remained stable without dilatation; however, it increased in the control group. The intervention group had femoral vein grafts with a significantly lower mean neointima-to-media ratio, and had vein grafts with an intima layer showing a significantly lower collagen density ratio than the control group. In conclusion, sirolimus-embedded silk-MN wrap in a vein graft model successfully delivered the drug to the intimal layer of the vein grafts. It prevented vein graft dilatation, avoiding shear stress and decreasing wall tension, and it inhibited neointimal hyperplasia.

Homology modeling of Forkhead box protein C2: identification of potential inhibitors using ligand and structure-based virtual screening.

Overexpression of Forkhead box protein C2 (FOXC2) has been associated with different types of carcinomas. FOXC2 plays an important role in the initiation and maintenance of the epithelial-mesenchymal transition (EMT) process, which is essential for the development of higher-grade tumors with an enhanced ability for metastasis. Thus, FOXC2 has become a therapeutic target for the development of anticancer drugs. MC-1-F2, the only identified experimental inhibitor of FOXC2, interacts with the full length of FOXC2. However, only the DNA-binding domain (DBD) of FOXC2 has resolved crystal structure. In this work, a three-dimensional (3D) structure of the full-length FOXC2 using homology modeling was developed and used for structure-based drug design (SBDD). The quality of this 3D model of the full-length FOXC2 was evaluated using MolProbity, ERRAT, and ProSA modules. Molecular dynamics (MD) simulation was also carried out to verify its stability. Ligand-based drug design (LBDD) was carried out to identify similar analogues for MC-1-F2 against 15 million compounds from ChEMBL and ZINC databases. 792 molecules were retrieved from this similarity search. De novo SBDD was performed against the full-length 3D structure of FOXC2 through homology modeling to identify novel inhibitors. The combination of LBDD and SBDD helped in gaining a better insight into the binding of MC-1-F2 and its analogues against the full length of the FOXC2. The binding free energy of the top hits was further investigated using MD simulations and MM/GBSA calculations to result in eight promising hits as lead compounds targeting FOXC2.

The effects of fluid absorption and plasma volume changes in athletes following consumption of various beverages.

BACKGROUND: To verify the hydration effects of oral rehydration solution (ORS) on athletes by comparing the degrees of fluid absorption and plasma volume changes following beverage consumption, including ORS. METHODS: Thirty-one participants visited the testing laboratory 4 times at 1-week intervals to consume 1 L of beverage (e.g., water, ORS, and two sports drinks [SpD]) for 30 min on each visit. The urine output was measured 4 times at 1 h, 2 h, 3 h, and 4 h after beverage consumption. A blood sample was collected 3 times at 1 h, 2 h, and 3 h after beverage consumption. Body weight was measured once in 4 h after beverage consumption. RESULTS: Body weight change was smaller for ORS than for water, SpD1, and SpD2 (p < 0.05). Cumulative urine output in 4 h was lower for ORS, SpD1, and SpD2 than for water (p < 0.05), and it was lower for ORS than for SpD2 (p < 0.05). BHI in 4 h was higher for ORS, SpD1, and SpD2 than for water (p < 0.05), and it was higher for ORS than for SpD2 (p < 0.05). There was no significant difference in PVC for different beverages at all test times, i.e.., 1 h, 2 h, and 3 h. CONCLUSIONS: We evaluated the hydration effects of the consumption of beverages, such as water, SpD, and ORS in athletes. ORS and SpD were more effective than water. A comparison between ORS and SpD showed that the result could vary depending on the type of SpD.

Co-Electrospun Silk Fibroin and Gelatin Methacryloyl Sheet Seeded with Mesenchymal Stem Cells for Tendon Regeneration.

Silk fibroin (SF) is a promising biomaterial for tendon repair, but its relatively rigid mechanical properties and low cell affinity have limited its application in regenerative medicine. Meanwhile, gelatin-based polymers have advantages in cell attachment and tissue remodeling but have insufficient mechanical strength to regenerate tough tissue such as tendons. Taking these aspects into account, in this study, gelatin methacryloyl (GelMA) is combined with SF to create a mechanically strong and bioactive nanofibrous scaffold (SG). The mechanical properties of SG nanofibers can be flexibly modulated by varying the ratio of SF and GelMA. Compared to SF nanofibers, mesenchymal stem cells (MSCs) seeded on SG fibers with optimal composition (SG7) exhibit enhanced growth, proliferation, vascular endothelial growth factor production, and tenogenic gene expression behavior. Conditioned media from MSCs cultured on SG7 scaffolds can greatly promote the migration and proliferation of tenocytes. Histological analysis and tenogenesis-related immunofluorescence staining indicate SG7 scaffolds demonstrate enhanced in vivo tendon tissue regeneration compared to other groups. Therefore, rational combinations of SF and GelMA hybrid nanofibers may help to improve therapeutic outcomes and address the challenges of tissue-engineered scaffolds for tendon regeneration.

Time-dependent pathobiological and physiological changes of implanted vein grafts in a canine model.

Although autologous vein grafting is essential, the high vein failure rate and specific clinical interventions are not clear, so a potential treatment is critically needed; thus, complex analyses of the relationship between pathobiological and physiological processes in preclinical are essential. The interposition of the femoral vein was performed in a canine model. Maximized expansion and velocity were measured at 8 weeks post-implantation, and a relative decrease was observed at 12 weeks. However, NI formation and NI/Media ratio significantly increased time dependently, and differences between the mechanical properties were observed. Additionally, RhoA-mediated TNF-α induced by rapid structural changes and high shear stress was confirmed. After adaptation to the arterial environment, vascular remodeling occurred by SMC proliferation and differentiation, apoptosis and autophagy were induced through YAP activity without vasodilation and RhoA activity. Our results show that understanding pathobiological processes in which time-dependent physiological changes contribute to vein failure can lead to a potential strategy. The implanted vein graft within the arterial environment undergoes pathobiological processes through RhoA and YAP activity, leading to pathophysiological changes.

Comparison of the analgesic efficacy of periarticular infiltration and pericapsular nerve group block for total hip arthroplasty: a randomized, non-inferiority study.

BACKGROUND: Motor-sparing regional anesthesia modalities, such as periarticular infiltration (PAI) and pericapsular nerve group (PENG) block, have become the mainstay of multimodal approaches used during total hip arthroplasty (THA). We hypothesized that the postoperative analgesia of the PENG block was non-inferior to that of the PAI. METHODS: Sixty patients were randomly allocated into two groups. The PAI group were injected with 100 mL of cocktail solution (ropivacaine 20 mL, ketorolac 2 mL, and epinephrine 1 mL mixed with normal saline) in periarticular tissues directly by the surgeon. The PENG group were injected with 30 mL of 0.5% ropivacaine in the iliopubic eminence plane by ultrasound. The primary outcome was the resting pain score 12 h after surgery, and the prespecified non-inferiority was 1. Additionally, the cumulative opioid consumption and quality of recovery were evaluated. RESULTS: The mean difference in pain score 12 h postoperatively between the PENG and PAI groups was 0.6 [95% confidence interval (CI): -0.8 to 2.0]. The upper 95% CI exceeded the non-inferiority margin of 1 at all postoperative time points. There was no difference in opioid consumptions and quality of recovery scores. CONCLUSIONS: PENG block provided comparable analgesia with PAI following THA. It is not conclusive that PENG is inferior or non-inferior to PAI based on our study. TRIAL REGISTRATION: Clinical Research information Service (CRIS, https://cris.nih.go.kr, KCT0006049).

Highly flexible and porous silk fibroin microneedle wraps for perivascular drug delivery.

Various perivascular drug delivery techniques have been demonstrated for localized post-treatment of intimal hyperplasia: a vascular inflammatory response caused by endothelial damages. Although most perivascular devices have focused on controlling the delivery duration of anti-proliferation drug, the confined and unidirectional delivery of the drug to the target tissue has become increasingly important. In addition, careful attention should also be paid to the luminal stability and the adequate exchange of vascular protein or cell between the blood vessel and extravascular tissue to avoid any side effect from the long-term application of any perivascular device. Here, a highly flexible and porous silk fibroin microneedle wrap (Silk MN wrap) is proposed to directly inject antiproliferative drug to the anastomosis sites while ensuring sufficient vascular exchanges. Drug-embedded silk MNs were transfer-molded on a highly flexible and porous silk wrap. The enhanced cell compatibility, molecular permeability, and flexibility of silk MN wrap guaranteed the structural integrity of blood vessels. Silk wrap successfully supported the silk MNs and induced multiple MN penetration to the target tissue. Over 28 days, silk MN wrap significantly inhibited intimal hyperplasia with a 62.1% reduction in neointimal formation.

Application of PLGA nanoparticles to enhance the action of duloxetine on microglia in neuropathic pain.

Duloxetine (DLX) is a selective serotonin and noradrenaline reuptake inhibitor (SNRI) used for the treatment of pain, but it has been reported to show side effects in 10-20% of patients. Its analgesic efficacy in central pain is putatively related to its influence on descending inhibitory neuronal pathways. However, DLX can also affect the activation of microglia. This study was performed to investigate whether PLGA nanoparticles (NPs), which are expected to enhance targeting to microglia, can improve the analgesic efficacy and limit the side effects of DLX. PLGA NPs encapsulating a low dose of DLX (DLX NPs) were synthesized and characterized and their localization was determined. The analgesic and anti-inflammatory effects of DLX NPs were evaluated in a spinal nerve ligation (SNL)-induced neuropathic pain model. The analgesic effect of DLX lasted for only a few hours and disappeared within 1 day. However, DLX NPs alleviated mechanical allodynia, and the effect was maintained for 1 week. DLX NPs were localized to the spinal microglia and suppressed microglial activation, phosphorylation of p38/NF-κB-mediated pathways and the production of inflammatory cytokines in the spinal dorsal horn of SNL rats. We demonstrated that DLX NPs can provide a prolonged analgesic effect by enhanced targeting of microglia. Our observations imply that DLX delivery through nanoparticle encapsulation allows drug repositioning with a prolonged analgesic effect, and reduces the potential side effects of abuse and overdose.

Single Administration of a Biodegradable, Separable Microneedle Can Substitute for Repeated Application of Eyedrops in the Treatment of Infectious Keratitis.

Infectious keratitis is mainly treated with topical antibiotics. To achieve and maintain the required therapeutic concentration in the cornea where the tear fluid continuously rinses the surface, the antibiotics must be frequently applied, even while the patient is sleeping, and oral medication is sometimes required. However, the inevitably poor compliance and avascular nature of the cornea decrease drug bioavailability. In this study, a single microneedle (MN) is injected into the cornea to substitute for the repeated application of eyedrops in the treatment of infectious keratitis. After comparing the mechanical integrity and drug release profiles of three different drug-tips, the drug-tip with the "high" drug concentration that releases 12.5 ng drug within 3 days is applied to a cornea to evaluate the transferability and in vivo drug release. In the treatment of infectious keratitis with repeated application of eyedrops for six consecutive days, a single MN injection is substituted for the initial 3 days of eyedrop applications. The progression remains similarly attenuated after 3 days without eyedrops, and comparable efficacy is achieved on day 6 when combined with delayed eyedrop treatment from day 3. Thus, the single administration of a biodegradable MN can substitute for the repeated application of eyedrops in the treatment of infectious keratitis.

Seed Layer Formation on Carbon Electrodes to Control Li2O2 Discharge Products for Practical Li-O2 Batteries with High Energy Density and Reversibility.

The high theoretical energy densities of lithium-air batteries (LAB) make this technology an attractive energy storage system for future mobility applications. Li2O2 growth process on the cathode relies on the surrounding chemical environment of electrolytes. Low conductivity and strong reactivity of Li2O2 discharge products can cause overpotential and induce side reactions in LABs, respectively, eventually leading to poor cyclability. The capacity and reversibility of LABs are highly susceptible to the morphology of the Li2O2 discharge products. Here, we identify for the first time that a seed layer formed by the combination of a cathode and an electrolyte determines the morphology of Li2O2 discharge products. This seed layer led to its high reversibility with a large areal capacity (up to 10 mAh/cm2). Excellent OER (oxygen evolution reaction) was achieved by the formation of a favorable interface between the carbon electrode and electrolyte, minimizing the decomposition of the electrolyte. These remarkable improvements in LAB performance demonstrate critical progress toward advancing LAB into practical uses, which would exploit good reversibility of LABs in pouch-type cell arrangements with 1.34 Ah.