High-Curie-Temperature Elastic Polymer Ferroelectric by Carbene Cross-Linking.

With the emergence of wearable electronics, ferroelectrics are poised to serve as key components for numerous potential applications. Currently, intrinsically elastic ferroelectrics featuring a network structure through a precise "slight cross-linking" approach have been realized. The resulting elastic ferroelectrics demonstrate a combination of stable ferroelectric properties and remarkable resilience under various strains. However, challenges arose as the cross-linking temperature was too high when integrating ferroelectrics with other functional materials, and the Curie temperature of this elastic ferroelectric was comparatively low. Addressing these challenges, we strategically chose a poly(vinylidene fluoride)-based copolymer with high vinylidene fluoride content to obtain a high Curie temperature while synthesizing a cross-linker with carbene intermediate for high reactivity to reduce the cross-linking temperature. At a relatively low temperature, we successfully fabricated elastic ferroelectrics through carbene cross-linking. The resulting elastic polymer ferroelectrics exhibit a higher Curie temperature and show a stable ferroelectric response under strains up to 50%. These materials hold significant potential for integration into wearable electronics.

Shh-Gli2-Runx2 inhibits vascular calcification.

BACKGROUND: In patients with chronic kidney disease (CKD), vascular calcification (VC) is common and is associated with a higher risk of all-cause mortality. Shh, one ligand for Hedgehog (Hh) signaling, participates in osteogenesis and several cardiovascular diseases. However, it remains unclear whether Shh is implicated in the development of VC. METHODS: Inorganic phosphorus 2.6 mM was used to induce vascular smooth muscle cells (VSMCs) calcification. Mice were fed with adenine diet supplement with 1.2% phosphorus to induce VC. RESULTS: Shh was decreased in VSMCs exposed to inorganic phosphorus, calcified arteries in mice fed with an adenine diet, as well as radial arteries from patients with CKD presenting VC. Overexpression of Shh inhibited VSMCs ostosteoblastic differentiation and calcification, whereas its silencing accelerated these processes. Likewise, mice treated with smoothened agonist (SAG; Hh signaling agonist) showed alleviated VC, and mice treated with cyclopamine (CPN; Hh signaling antagonist) exhibited severe VC. Additionally, overexpression of Gli2 significantly reversed the pro-calcification effect of Shh silencing on VSMCs, suggesting that Shh inhibited VC via Gli2. Mechanistically, Gli2 interacted with Runx2 and promoted its ubiquitin proteasomal degradation, therefore protecting against VC. Of interest, the pro-degradation effect of Gli2 on Runx2 was independent of Smurf1 and Cullin4B. CONCLUSIONS: Our study provided deeper insight to the pathogenesis of VC, and Shh might be a novel potential target for VC treatment.

Modified failproof physics-informed neural network framework for fast and accurate optical fiber transmission link modeling.

Physics-informed neural networks (PINNs) have recently emerged as an important and ground-breaking technique in scientific machine learning for numerous applications including in optical fiber communications. However, the vanilla/baseline version of PINNs is prone to fail under certain conditions because of the nature of the physics-based regularization term in its loss function. The use of this unique regularization technique results in a highly complex non-convex loss landscape when visualized. This leads to failure modes in PINN-based modeling. The baseline PINN works very well as an optical fiber model with relatively simple fiber parameters and for uncomplicated transmission tasks. Yet, it struggles when the modeling task becomes relatively complex, reaching very high error, for example, numerous modeling tasks/scenarios in soliton communication and soliton pulse development in special fibers such as erbium-doped dispersion compensating fibers. We implement two methods to circumvent the limitations caused by the physics-based regularization term to solve this problem, namely, the so-called scaffolding technique for PINN modeling and the progressive block learning PINN modeling strategy to solve the nonlinear Schrödinger equation (NLSE), which models pulse propagation in an optical fiber. This helps PINN learn more accurately the dynamics of pulse evolution and increases accuracy by two to three orders of magnitude. We show in addition that this error is not due to the depth or architecture of the neural network but a fundamental issue inherent to PINN by design. The results achieved indicate a considerable reduction in PINN error for complex modeling problems, with accuracy increasing by up to two orders of magnitude.

Autonomous Microlasers for Profiling Extracellular Vesicles from Cancer Spheroids.

Self-propelled micro/nanomotors are emergent intelligent sensors for analyzing extracellular biomarkers in circulating biological fluids. Conventional luminescent motors are often masked by a highly dynamic and scattered environment, creating challenges to characterize biomarkers or subtle binding dynamics. Here we introduce a strategy to amplify subtle signals by coupling strong light-matter interactions on micromotors. A smart whispering-gallery-mode microlaser that can self-propel and analyze extracellular biomarkers is demonstrated through a liquid crystal microdroplet. Lasing spectral responses induced by cavity energy transfer were employed to reflect the abundance of protein biomarkers, generating exclusive molecular labels for cellular profiling of exosomes derived from 3D multicellular cancer spheroids. Finally, a microfluidic biosystem with different tumor-derived exosomes was employed to elaborate its sensing capability in complex environments. The proposed autonomous microlaser exhibits a promising method for both fundamental biological science and applications in drug screening, phenotyping, and organ-on-chip applications.

Elastic Relaxor Ferroelectric by Thiol-ene Click Reaction.

As ferroelectrics hold significance and application prospects in wearable devices, the elastification of ferroelectrics becomes more and more important. Nevertheless, achieving elastic ferroelectrics requires stringent synthesis conditions, while the elastification of relaxor ferroelectric materials remains unexplored, presenting an untapped potential for utilization in energy storage and actuation for wearable electronics. The thiol-ene click reaction offers a mild and rapid reaction platform to prepare functional polymers. Therefore, we employed this approach to obtain an elastic relaxor ferroelectric by crosslinking an intramolecular carbon-carbon double bonds (CF=CH) polymer matrix with multiple thiol groups via a thiol-ene click reaction. The resulting elastic relaxor ferroelectric demonstrates pronounced relaxor-type ferroelectric behaviour. This material exhibits low modulus, excellent resilience, and fatigue resistance, maintaining a stable ferroelectric response even under strains up to 70 %. This study introduces a straightforward and efficient approach for the construction of elastic relaxor ferroelectrics, thereby expanding the application possibilities in wearable electronics.

Simultaneous bond-selective deuterium-based isotopic labeling sensing with disposable ultra-miniature CARS fiber probe.

Deuterium-based isotopic labeling is an important technique for tracking cellular metabolism with the Raman signals analysis of low-wavenumber (LW) C-D bonds and high-wavenumber (HW) C-H bonds. We propose and demonstrate a disposable ultra-miniature fiber probe to detect LW and HW coherent anti-Stokes Raman scattering (CARS) spectra for deuterated compounds simultaneously and bond-selectively sensing. The 10.78 µm diameter disposable fiber probe, comprised of focusing taper as fiber probe head and time-domain walk-off eliminating fiber section with designed length, realizes wide-frequency-interval dual Stokes pulse delivering and focusing. The fiber probe enables quantitative concentration determination with resolution down to 11 mM. The chemical vibration modes of LW region C-D bonds and HW region C-H bonds of the mixture samples of organic compounds and their deuterated counterparts in a simulated cell are simultaneously excited and characterized. The CARS disposable fiber probe introduces a promising handle for in vivo biochemical detection based on isotopic labeling sensing.

Ginkgolide A targets forkhead box O1 to protect against lipopolysaccharide-induced septic cardiomyopathy.

Ginkgolide A (GA), a main terpenoid extracted from Ginkgo biloba, possesses biological activities such as anti-inflammatory, anti-tumor, and liver protection. However, the inhibitory effects of GA on septic cardiomyopathy remain unclear. This study aimed to explore the effects and mechanisms of GA in countering sepsis-induced cardiac dysfunction and injury. In lipopolysaccharide (LPS)-induced mouse model, GA alleviated mitochondrial injury and cardiac dysfunction. GA also significantly reduced the production of inflammatory and apoptotic cells, the release of inflammatory indicators, and the expression of oxidative stress-associated and apoptosis-associated markers, but increased the expression of pivotal antioxidant enzymes in hearts from LPS group. These results were consistent with those of in vitro experiments based on H9C2 cells. Database analysis and molecular docking suggested that FoxO1 was targeted by GA, as shown by stable hydrogen bonds formed between GA with SER-39 and ASN-29 of FoxO1. GA reversed LPS-induced downregulation of nucleus FoxO1 and upregulation of p-FoxO1 in H9C2 cells. FoxO1 knockdown abolished the protective properties of GA in vitro. KLF15, TXN2, NOTCH1, and XBP1, as the downstream genes of FoxO1, also exerted protective effects. We concluded that GA could alleviate LPS-induced septic cardiomyopathy via binding to FoxO1 to attenuate cardiomyocyte inflammation, oxidative stress, and apoptosis.

Wideband Multichannel Nyquist-Spaced Long-Haul Optical Transmission Influenced by Enhanced Equalization Phase Noise.

Enhanced equalization phase noise (EEPN), generated from the uncompensated dispersion experienced by laser phase noises, can cause serious damage to the transmission quality of optical fiber systems. In this work, the performance of a wideband Nyquist-spaced long-haul nonlinear optical fiber communication systems suffering from EEPN is investigated and discussed through split-step numerical simulations and analytical models based on the perturbation analysis, in the cases of digital nonlinearity compensation (NLC) and electronic dispersion compensation (EDC). The efficiency and the accuracy of the analytical models were validated via simulations, considering the different symbol rates and modulation formats. The performance of the C-band transmission was comprehensively studied based on the model. Our results reveal that the growth of symbol rates and transmission distances aggravates the distortions in the C-band system.

Analytical optimization of wideband nonlinear optical fiber communication systems.

In the design of fiber links for both continental and transoceanic optical communication systems, the optimization of span length is of high importance from both performance and cost perspectives. In this work, the maximization of signal-to-noise ratio (SNR) is investigated by optimizing the span length in wideband (up to 4.5-THz) Nyquist-spaced optical fiber communication systems. A simple and accurate closed-form expression of the optimal span length is provided, and a quick estimation of SNR is also described for practically feasible and cost-effective span length values.

Non-Invasive Local Acoustic Therapy Ameliorates Diabetic Heart Fibrosis by Suppressing ACE-Mediated Oxidative Stress and Inflammation in Cardiac Fibroblasts.

PURPOSE: The extent of myocardial fibrosis is closely related to the prognosis of diabetic cardiomyopathy (DCM). Low-intensity pulsed ultrasound (LIPUS) has been reported to have multiple biological effects. However, the effect of LIPUS on diabetic heart fibrosis remains unclear. The present study aimed to investigate the effect of LIPUS on diabetic heart fibrosis and explore its underlying mechanisms. METHODS AND RESULTS: High glucose (HG) was applied to cultured neonatal rat cardiac fibroblasts (NRCFs) to mimic the in vivo hyperglycemia microenvironment. LIPUS (19.30 mW/cm2 to 77.20 mW/cm2) dose-dependently inhibited HG-induced fibrotic response in NRCFs. Also, LIPUS downregulated NADPH oxidase 4 (NOX4)-associated oxidative stress and nod-like receptor protein-3 (NLRP3) inflammasome activation in NRCFs. In vivo, diabetes in mice was induced with streptozotocin (STZ). Mice in the LIPUS group and STZ + LIPUS group were treated with LIPUS (77.20 mW/cm2) twice a week for 12 weeks and then euthanized at 12 weeks or 24 weeks post-diabetes. Treatment with LIPUS significantly ameliorated the progression of cardiac fibrosis (Masson staining 6.5 ± 2.3% vs. 2.8 ± 1.5%, P < 0.001) and dysfunction (E/A ratio 1.35 ± 0.14 vs. 1.59 ± 0.11, P < 0.05), as well as NOX4-associated oxidative stress (relative expression fold of NOX4 1.43 ± 0.12 vs. 1.07 ± 0.10, P < 0.01; relative DHE fluorescence 1.51 ± 0.13 vs. 1.28 ± 0.06, P < 0.05) and NLRP3 inflammasome activation (relative expression fold of NLRP3 1.57 ± 0.12 vs. 1.05 ± 0.16, P < 0.01), at 12 weeks post-diabetes. At 24 weeks post-diabetes, the heart function in diabetic mice treated with LIPUS was still significantly better than untreated diabetic mice (E/A ratio 1.08 ± 0.12 vs. 1.49 ± 0.14, P < 0.001). Further exploration revealed that LIPUS significantly attenuated the upregulated angiotensin-converting enzyme (ACE) and angiotensin II (AngII), in both HG-induced NRCFs and diabetic hearts (relative expression of ACE in myocardium 3.77 ± 0.55 vs. 1.07 ± 0.13, P < 0.001; AngII in myocardium 115.5 ± 21.77 ng/ml vs. 84.28 ± 9.03 ng/ml, P < 0.01). Captopril, an ACE inhibitor, inhibited NOX4-associated oxidative stress and NLRP3 inflammasome activation in both HG-induced NRCFs and diabetic hearts. CONCLUSION: Our results indicate that non-invasive local LIPUS therapy attenuated heart fibrosis and dysfunction in diabetic mice and the effect could be largely preserved at least 12 weeks after suspending LIPUS stimulation. LIPUS ameliorated diabetic heart fibrosis by inhibiting ACE-mediated NOX4-associated oxidative stress and NLRP3 inflammasome activation in cardiac fibroblasts. Our study may provide a novel therapeutic approach to hamper the progression of diabetic heart fibrosis.

Effect of Magnesium Supplementation on Chronic Kidney Disease-Mineral and Bone Disorder in Hemodialysis Patients: A Meta-Analysis of Randomized Controlled Trials.

OBJECTIVES: Research about the effects of magnesium (Mg) supplementation on chronic kidney disease-mineral bone disorder (CKD-MBD) among hemodialysis (HD) patients is controversial. Thus, we conducted a meta-analysis to examine Mg supplementation's effects on CKD-MBD in patients requiring dialysis. METHODS: The PubMed and EMBASE databases were searched for English language studies up to September 2020. The main indicators of our study were changes in serum Mg, calcium (Ca), phosphate, parathyroid hormone (PTH), and C-reactive protein levels, and carotid intima-media thickness (CIMT) after Mg supplementation. Mg efficacy was evaluated by weighted mean difference (WMD) and confidence intervals (CIs), and subgroup analyses of intervention type and intervention duration were also performed. RESULTS: Eight eligible studies comprising 309 HD patients were included in our meta-analysis. Mg supplementation alone produced a negative effect on serum PTH levels (WMD = -236.56; 95% CI -349.71 to -123.41) and CIMT (WMD = -0.18; 95% CI -0.34 to -0.01). A subgroup analysis based on intervention type showed a significant improvement in serum Mg (WMD = 1.08; 95% CI 0.51-1.64) and Ca (WMD = -0.50; 95% CI -0.77 to -0.23) levels when Mg was administered via dialysate and oral medication, respectively. Different intervention durations had no effect on serum Mg levels. Mg supplementation had no significant effect on serum phosphate (WMD = -0.25; 95% CI -0.64 to 0.14) and C-reactive protein levels (WMD = -0.02; 95% CI -2.80 to 2,76). CONCLUSIONS: Our results showed that Mg supplementation alone could improve CKD-MBD by regulating serum Ca and PTH metabolism and decreasing CIMT among HD patients.

A Bidirectional Wavelength Division Multiplexed (WDM) Free Space Optical Communication (FSO) System for Deployment in Data Center Networks (DCNs).

Data centers are crucial to the growth of cloud computing. Next-generation data center networks (DCNs) will rely heavily on optical technology. Here, we have investigated a bidirectional wavelength-division-multiplexed (WDM) free space optical communication (FSO) system for deployment in optical wireless DCNs. The system was evaluated for symmetric 10 Gbps 16-quadrature amplitude modulation (16-QAM) intensity-modulated orthogonal frequency-division multiplexing (OFDM) downstream signals and 10 Gbps on-off keying (OOK) upstream signals, respectively. The transmission of optical signals over an FSO link is demonstrated using a gamma-gamma channel model. According to the bit error rate (BER) results obtained for each WDM signal, the bidirectional WDM-FSO transmission could achieve 320 Gbps over 1000 m free space transmission length. The results show that the proposed FSO topology offers an excellent alternative to fiber-based optical interconnects in DCNs, allowing for high data rate bidirectional transmission.

Distributed Raman Amplification for Fiber Nonlinearity Compensation in a Mid-Link Optical Phase Conjugation System.

In this paper, we review different designs of distributed Raman amplifiers which have been proposed to minimize the signal power profile asymmetry in mid-link optical phase conjugation systems. We demonstrate how the symmetrical signal power profiles along the fiber can be achieved using various distributed Raman amplification techniques in the single-span and more realistic multi-span circumstances. In addition, we show the theoretically predicted results of the Kerr nonlinear product reduction with different Raman techniques in mid-link optical phase conjugator systems, and then in-line/long-haul transmission performance using numerical simulations.

The balance between AIM2-associated inflammation and autophagy: the role of CHMP2A in brain injury after cardiac arrest.

BACKGROUND: Activation of the absent in melanoma 2 (AIM2) inflammasome and impaired autophagosome clearance in neurons contribute significantly to cardiac arrest and return of spontaneous circulation (CA-ROSC) injury, while the mechanism by which the AIM2 inflammasome is regulated and relationship between the processes remain poorly understood. Recently, charged multivesicular body protein 2A (CHMP2A), a subunit of endosomal sorting complex required for transport (ESCRT), was shown to regulate phagophore closure, and its depletion led to the accumulation of autophagosomes and induced cell death. Here, we investigated whether CHMP2A-mediated autophagy was an underlying mechanism of AIM2-associated inflammation after CA-ROSC and explored the potential link between the AIM2 inflammasome and autophagy under ischemic conditions. METHODS: AIM2 inflammasome activation and autophagic flux in the cortex were assessed in the CA-ROSC rat model. We injected LV-Vector or LV-CHMP2A virus into the motor cortex with stereotaxic coordinates and divided the rats into four groups: Sham, CA, CA+LV-Vector, and CA+LV-CHMP2A. Neurologic deficit scores (NDSs), balance beam tests, histopathological injury of the brain, and expression of the AIM2 inflammasome and proinflammatory cytokines were analyzed. RESULTS: AIM2 inflammasome activation and increased interleukin 1 beta (IL-1ß) and IL-18 release were concurrent with reduced levels of CHMP2A-induced autophagy in CA-ROSC rat neurons. In addition, silencing CHMP2A resulted in autophagosome accumulation and decreased autophagic degradation of the AIM2 inflammasome. In parallel, a reduction in AIM2 contributed to autophagy activation and mitigated oxygen-glucose deprivation and reperfusion (OGD-Rep)-induced inflammation. Notably, CHMP2A overexpression in the cortex hindered neuroinflammation, protected against ischemic brain damage, and improved neurologic outcomes after CA. CONCLUSIONS: Our results support a potential link between autophagy and AIM2 signaling, and targeting CHMP2A may provide new insights into neuroinflammation in the early phase during CA-ROSC.

Deep intelligent spectral labelling and receiver signal distribution for optical links.

A unique automatic receiver signal distribution strategy is proposed for private optical networks based on the concept of non-orthogonality. A non-orthogonal signal waveform can compress the spectral bandwidth, which not only fits a signal in a bandwidth limited scenario, but also enables the compression ratio information for labelling. Depending on a unique value of spectral compression, an end user destination can be correlated. A network edge node will rely on deep learning to intelligently identify each raw signal and forward it to corresponding end users with no sophisticated digital signal pre-processing. In this case, signal identification and distribution are faster while computationally intensive signal compensation and detection will be shifted to each end user since the receiver is highly dynamic and user-defined in private optical networks. An intelligent signal classifier will be trained considering various fiber transmission factors such as transmission distance, training dataset size and launch power. At the end, a universal classifier is obtained, which can be used to identify signals in a system for any fiber transmission distance and launch power.

Information rates in Kerr nonlinearity limited optical fiber communication systems.

Achievable information rates of optical communication systems are inherently limited by nonlinear distortions due to the Kerr effect occurred in optical fibres. These nonlinear impairments become more significant for communication systems with larger transmission bandwidths, closer channel spacing and higher-order modulation formats. In this paper, the efficacy of nonlinearity compensation techniques, including both digital back-propagation and optical phase conjugation, for enhancing achievable information rates in lumped EDFA- and distributed Raman-amplified fully-loaded C -band systems is investigated considering practical transceiver limitations. The performance of multiple modulation formats, such as dual-polarisation quadrature phase shift keying (DP-QPSK), dual-polarisation 16 -ary quadrature amplitude modulation (DP-16QAM), DP-64QAM and DP-256QAM, has been studied in C -band systems with different transmission distances. It is found that the capabilities of both nonlinearity compensation techniques for enhancing achievable information rates strongly depend on signal modulation formats as well as target transmission distances.

Applications of liquid crystals in biosensing.

Liquid crystals (LCs), as a promising branch of highly-sensitive, quick-response, and low-cost materials, are widely applied to the detection of weak external stimuli and have attracted significant attention. Over the past decade, many research groups have been devoted to developing LC-based biosensors due to their self-assembly potential and functional diversity. In this paper, recent investigations on the design and application of LC-based biosensors are reviewed, based on the phenomenon that the orientation of LCs can be directly influenced by the interactions between biomolecules and LC molecules. The sensing principle of LC-based biosensors, as well as their signal detection by probing interfacial interactions, is described to convert, amplify, and quantify the information from targets into optical and electrical parameters. Furthermore, commonly-used LC biosensing targets are introduced, including glucose, proteins, enzymes, nucleic acids, cells, microorganisms, ions, and other micromolecules that are critical to human health. Due to their self-assembly potential, chemical diversity, and high sensitivity, it has been reported that tunable stimuli-responsive LC biosensors show bright perspectives and high superiorities in biological applications. Finally, challenges and future prospects are discussed for the fabrication and application of LC biosensors to both enhance their performance and to realize their promise in the biosensing industry.

Low-intensity pulsed ultrasound prevents prolonged hypoxia-induced cardiac fibrosis through HIF-1α/DNMT3a pathway via a TRAAK-dependent manner.

Hypoxia-induced cardiac fibrosis is an important pathological process in cardiovascular disorders. This study aimed to determine whether low-intensity pulsed ultrasound (LIPUS), a novel and safe apparatus, could alleviate hypoxia-induced cardiac fibrosis, and to elucidate the underlying mechanisms. Hypoxia (1% O2 ) and transverse aortic constriction (TAC) were performed on neonatal rat cardiac fibroblasts and mice to induce cardiac fibrosis, respectively. LIPUS irradiation was applied for 20 minutes every 6 hours for a total of 2 times in vitro, and every 2 days from 1 week before surgery to 4 weeks after surgery in vivo. We found that LIPUS dose-dependently attenuated hypoxia-induced cardiac fibroblast phenotypic conversion in vitro, and ameliorated TAC-induced cardiac fibrosis in vivo. Hypoxia significantly upregulated the nuclear protein expression of hypoxia-inducible factor-1α (HIF-1α) and DNA methyltransferase 3a (DNMT3a). LIPUS pre-treatment reversed the elevated expression of HIF-1α, and DNMT3a. Further experiments revealed that HIF-1α stabilizer dimethyloxalylglycine (DMOG) hindered the anti-fibrotic effect of LIPUS, and hampered LIPUS-mediated downregulation of DNMT3a. DNMT3a small interfering RNA (siRNA) prevented hypoxia-induced cardiac fibrosis. Results also showed that the mechanosensitive protein-TWIK-related arachidonic acid-activated K+ channel (TRAAK) messenger RNA (mRNA) expression was downregulated in hypoxia-induced cardiac fibroblasts, and TAC-induced hearts. TRAAK siRNA impeded LIPUS-mediated anti-fibrotic effect and downregulation of HIF-1α and DNMT3a. Above results indicated that LIPUS could prevent prolonged hypoxia-induced cardiac fibrosis through TRAAK-mediated HIF-1α/DNMT3a signalling pathway.

Heterogeneous-frequency-dual-pulse chain and weak FBG array for quasi-distributed acoustic sensing with improved response bandwidth.

By continuously injecting four groups of heterogeneous frequency dual pulses into the sensing fiber with weak fiber Bragg gratings (WFBGs), a quasi-distributed acoustic sensing method based on frequency-division multiplexing is proposed. Each group of pulses generates interference signals with different carrier frequencies after being reflected by the WFBGs. Through the discrete Fourier transform phase demodulation method, each carrier frequency interference signal is demodulated and then the phase is spliced. The feasibility of this method is theoretically analyzed, and a detection with a bandwidth of 2 kHz is realized on a 70 km sensing fiber with a spatial resolution of 10 m.

Fractionated carbon dioxide (CO2) laser treatment contributes to trans-nail penetration of rhodamine B and changes of cytokine microenvironment.

This study is to determine the role of the fractional CO2 laser in topical drug delivery and the impact of local immune responses. Experimental rabbit nails were treated with fractionated CO2 laser at varied fluencies of 20 mJ, 25 mJ, and 30 mJ and half of which were coated with rhodamine B (RhB). Histological examination was performed by hematoxylin and eosin staining; the penetration of RhB was assessed by the use of confocal laser scanning microscopy; and the expressions of IFN-γ and IL-4 mRNA in situ were detected by means of qPCR at 12 h, 24 h, 3 days, and 7 days post-laser irritation. The fractional CO2 laser could generate microscopic treatment zones in nail plates, and the depths of these micropores as well as the permeation of RhB in nails increased significantly in an energy-dependent manner. Importantly, the laser irritation led an upregulation of local IFN-γ mRNA expression accompanied by a downregulation of IL-4 mRNA expression. The ultrapulsed ablative fractionated CO2 laser may assist topical drug delivery, and may drive stronger local Th1 responses due to an imbalance of IFN-γ/IL-4 expressions, suggesting that the combination of ablative fractionated CO2 laser with topical agents would be an effective option for the treatment of onychomycosis.