High Q-factor Polymer Microring Resonators Realized by Versatile Damascene Soft Nanoimprinting Lithography.

High-quality-factor microring resonators are highly desirable in many applications. Fabricating a microring resonator typically requires delicate instruments to ensure a smooth side wall of waveguides and 100-nm critical feature size in the coupling region. In this work, we demonstrate a new method "damascene soft nanoimprinting lithography" that can create high-fidelity waveguide by simply backfill an imprinted cladding template with a high refractive index polymer core. This method can easily realize high Q-factor polymer microring resonators (e.g., ~5 x 105 around 770 nm wavelength) without the use of any expensive instruments and can be conducted in a normal lab environment. The high Q-factors can be attributed to the residual layer-free feature and controllable meniscus cross-section profile of the filled polymer core. Furthermore, the new method is compatible with different polymers, yields low fabrication defects, enables new functionalities, and allows flexible substrate. These benefits can broaden the applicability of the fabricated microring resonator.

PDIA3 orchestrates effector T cell program by serving as a chaperone to facilitate the non-canonical nuclear import of STAT1 and PKM2.

Dysregulated T cell activation underpins the immunopathology of rheumatoid arthritis (RA), yet the machineries that orchestrate T cell effector program remain incompletely understood. Herein, we leveraged bulk and single-cell RNA sequencing data from RA patients and validated protein disulfide isomerase family A member 3 (PDIA3) as a potential therapeutic target. PDIA3 is remarkably upregulated in pathogenic CD4 T cells derived from RA patients and positively correlates with C-reactive protein level and disease activity score 28. Pharmacological inhibition or genetic ablation of PDIA3 alleviates RA-associated articular pathology and autoimmune responses. Mechanistically, T cell receptor signaling triggers intracellular calcium flux to activate NFAT1, a process that is further potentiated by Wnt5a under RA settings. Activated NFAT1 then directly binds to the Pdia3 promoter to enhance the expression of PDIA3, which complexes with STAT1 or PKM2 to facilitate their nuclear import for transcribing T helper 1 (Th1) and Th17 lineage-related genes, respectively. This non-canonical regulatory mechanism likely occurs under pathological conditions, as PDIA3 could only be highly induced following aberrant external stimuli. Together, our data support that targeting PDIA3 is a vital strategy to mitigate autoimmune diseases, such as RA, in clinical settings.

Scaling down the dimensions of a Fabry-Perot polymer film acoustic sensor for photoacoustic endoscopy.

Significance: A Fabry-Perot (FP) polymer film sensor can be used to detect acoustic waves in a photoacoustic endoscope (PAE) if the dimensions can be adequately scaled down in size. Current FP sensors have limitations in size, sensitivity, and array configurability. Aim: We aim to characterize and demonstrate the imaging performance of a miniature FP sensor to evaluate the effects of reduced size and finite dimensions. Approach: A transfer matrix model was developed to characterize the frequency response of a multilayer miniature FP sensor. An analytical model was derived to describe the effects of a substrate with finite thickness. Finite-element analysis was performed to characterize the temporal response of a sensor with finite dimensions. Miniature 2×2 mm2 FP sensors were designed and fabricated using gold films as reflective mirrors on either side of a parylene C film deposited on a glass wafer. A single-wavelength laser was used to interrogate the sensor using illumination delivered by fiber subprobes. Imaging phantoms were used to verify FP sensor performance, and in vivo images of blood vessels were collected from a live mouse. Results: The finite thickness substrate of the FP sensor resulted in echoes in the time domain signal that could be removed by back filtering. The substrate acted as a filter in the frequency domain. The finite lateral sensor dimensions produced side waves that could be eliminated by surface averaging using an interrogation beam with adequate diameter. The fabricated FP sensor produced a noise-equivalent pressure = 0.76 kPa, bandwidth of 16.6 MHz, a spectral full-width at-half-maximum = 0.2886 nm, and quality factor Q=2694. Photoacoustic images were collected from phantoms and blood vessels in a live mouse. Conclusions: A miniature wafer-based FP sensor design has been demonstrated with scaled down form factor for future use in PAE.

Fabrication of a translational photoacoustic needle sensing probe for interstitial photoacoustic spectral analysis.

In our previous study, we demonstrated the feasibility of using an all-optical interstitial photoacoustic (PA) needle sensing probe for quantitative study of tissue architectures with PA spectral analysis (PASA). In this work, we integrated the optical components into an 18 G steel needle sheath for clinical translation. The dimensions of the needle probe are identical to those of a core biopsy probe and are fully compatible with standard procedures such as prostate biopsy. To our knowledge, this is the first interstitial PA probe that can acquire signals with sufficient temporal length for statistics-based PASA. We treated the inner surface of the steel needle sheath and successfully suppressed the vibrational PA signals generated at the surface. Purposed at boosting the measurement sensitivity and extending sensing volume, we upgraded the Fabry-Pérot hydrophone with a plano-concave structure. The performance of the translational needle PA sensing probe was examined with phantoms containing microspheres. The trend of the linear spectral slopes shows negatively correlated to the microsphere dimensions while the midband-fits are positively correlated to microsphere diameters and concentrations. The PASA quantifications show the ability to differentiate microspheres with varied dimensions.

Universal Color Retrofit to Polymer-Based Radiative Cooling Materials.

Polymers with broad infrared emission and negligible solar absorption have been identified as promising radiative cooling materials to offer a sustainable and energy-saving venue. Although practical applications desire color for visual appearance, the current coloration strategies of polymer-based radiative cooling materials are constrained by material, cost, and scalability. Here, we demonstrate a universally applicable coloration strategy for polymer-based radiative cooling materials by nanoimprinting. By modulating light interference with periodic structures on polymer surfaces, specular colors can be induced while maintaining the hemispheric optical responses of radiative cooling polymers. The retrofit strategy is exemplified by four different polymer films with a minimum impact on optical responses compared to the pristine films. Polymer films feature low solar absorption of 1.7-3.7%, and daytime sub-ambient cooling is exemplified in the field test. The durability of radiative cooling and color are further validated by dynamic spectral analysis. Finally, the potential roll-to-roll manufacturing empowers a scalable, low-cost, and easy-retrofitting solution for colored radiative cooling films.

Anion-Exchange Blue Perovskite Quantum Dots for Efficient Light-Emitting Devices.

In this study, blue perovskite quantum dots (PQDs) were prepared using didodecyldimethylammonium bromide (DDAB), which can passivate surface defects caused by the loss of surface ligands and reduce particle size distribution. After the passivation of DDAB, blue CsPbClxBr3-x PQDs dispersed in n-octane produced a more compact and uniform PQD thin film than the non-passivated ones. The resulting device showed a stabile lifetime, and an EL peak of 470 nm and a maximum EQE of 1.63% were obtained at an operating voltage of 2.6 V and a current density of 0.34 mA/cm2. This work aims to provide a simple method to prepare blue-emitting PQDs and high-performance PQD-based light-emitting devices.

Assessment of prostate cancer progression using a translational needle photoacoustic sensing probe: Preliminary study with intact human prostates ex-vivo.

In our previous studies, we demonstrated the ability of an interstitial all-optical needle photoacoustic (PA) sensing probe and PA spectral analysis (PASA) to assess the aggressiveness of prostate cancer. In this clinical translation investigation, we integrated the optical components of the needle PA sensing probe into a 18G steel needle. The translational needle PA sensing probe was evaluated using intact human prostates in a simulated ultrasound-guided transperineal prostate biopsy. PA signals were acquired at 1220 nm, 1370 nm, 800 nm and 266 nm at each interstitial measurement location and quantified by PASA within the frequency range of 8-28 MHz. The measurement locations were stained for establishing spatial correlations between the quantitative measurements and the histological diagnosing. Most of the quantitative PA assessments reveal statistically significant differences between the benign and cancerous regions. Multivariate analysis combining the PASA quantifications shows an accuracy close to 90% in differentiating the benign and cancerous regions in the prostates.

Cranberry-Derived Proanthocyanidins Potentiate ß-Lactam Antibiotics against Resistant Bacteria.

The emergence and spread of extended-spectrum ß-lactamases (ESBLs), metallo-ß-lactamases (MBLs), or variant low-affinity penicillin-binding proteins (PBPs) pose a major threat to our ability to treat bacterial infection using ß-lactam antibiotics. Although combinations of ß-lactamase inhibitors with ß-lactam agents have been clinically successful, there are no MBL inhibitors in current therapeutic use. Furthermore, recent clinical use of new-generation cephalosporins targeting PBP2a, an altered PBP, has led to the emergence of resistance to these antimicrobial agents. Previous work shows that natural polyphenols such as cranberry-extracted proanthocyanidins (cPAC) can potentiate non-ß-lactam antibiotics against Gram-negative bacteria. This study extends beyond previous work by investigating the in vitro effect of cPAC in overcoming ESBL-, MBL-, and PBP2a-mediated ß-lactam resistance. The results show that cPAC exhibit variable potentiation of different ß-lactams against ß-lactam-resistant Enterobacteriaceae clinical isolates as well as ESBL- and MBL-producing E. coli We also discovered that cPAC have broad-spectrum inhibitory properties in vitro on the activity of different classes of ß-lactamases, including CTX-M3 ESBL and IMP-1 MBL. Furthermore, we observe that cPAC selectively potentiate oxacillin and carbenicillin against methicillin-resistant but not methicillin-sensitive staphylococci, suggesting that cPAC also interfere with PBP2a-mediated resistance. This study motivates the need for future work to identify the most bioactive compounds in cPAC and to evaluate their antibiotic-potentiating efficacy in vivoIMPORTANCE The emergence of ß-lactam-resistant Enterobacteriaceae and staphylococci compromises the effectiveness of ß-lactam-based therapy. By acquisition of ESBLs, MBLs, or PBPs, it is highly likely that bacteria may become completely resistant to the most effective ß-lactam agents in the near future. In this study, we described a natural extract rich in proanthocyanidins which exerts adjuvant properties by interfering with two different resistance mechanisms. By their broad-spectrum inhibitory ability, cranberry-extracted proanthocyanidins could have the potential to enhance the effectiveness of existing ß-lactam agents.

Electrokinetic behavior of a pH-regulated dielectric cylindrical nanopore.

A continuum model is adopted to describe the electrokinetic behavior of a pH-regulated cylindrical nanopore, the surface of which has charge-regulated carboxyl groups. We focus on the influences of the permittivity of the nanopore material, nanopore size, salt concentration, and solution pH on this behavior, and the underlying mechanisms. The influence of the nanopore permittivity becomes significant when a nanopore is shorter than ca. 50 nm. It is interesting to observe that if it is longer than ca. 100 nm, the nanopore conductance decreases with increasing permittivity. If it is sufficiently short, the conductance increases with increasing permittivity. If the nanopore length takes a medium level, the conductance is insensitive to the variation in the permittivity. For a short nanopore (~20 nm), the conductivity increases with increasing permittivity. However, if pH is sufficiently high, it becomes insensitive to permittivity. Although the larger the permittivity the greater the conductivity, in general, this effect becomes insignificant when the bulk salt concentration is sufficiently high, implying that the effect of membrane polarization is important only if the bulk salt concentration is sufficiently low.

Modified technique of advanced core decompression for treatment of femoral head osteonecrosis.

BACKGROUND: Osteonecrosis of the femoral head (ONFH) is a destructive condition most commonly affecting young and middle-aged patients. The leading consequence of ONFH is often a significant articular disability. Effective joint-preserving surgical treatments are urgently needed for patients with early stage ONFH when outcomes of treatment are in general better than the advanced stage disease. AIM: To introduce a new surgery procedure called percutaneous expanded core decompression and mixed bone graft technique, which is a new way of joint-preserving surgical treatments. METHODS: The clinical data of 6 patients with ONFH diagnosed and treated with the procedure called percutaneous expanded core decompression and mixed bone graft technique at The First Hospital of Qiqihar from March 2013 to August 2019 were retrospectively analyzed; the follow-up ended in December 2019. RESULTS: There were 6 male patients with an average age of 43 years in our study. Gratifying results have been obtained from the comparison of Harris hip score, visual analogue scale, and imaging examination before and after operation. CONCLUSION: This new modified technique is simple, safe, and reliable. No serious perioperative complications were observed in our cases. Advantages of the single blade expandable reamer are obvious. The adjuvant substance is inexpensive and easy to obtain. Thus, this technique is an effective joint-preserving surgical treatment for patients with early stage of ONFH.

Ion current rectification behavior of a nanochannel having nonuniform cross-section.

Due to its versatile applications in biotechnology, ion current rectification (ICR), which arises from the asymmetric nature of the ion transport in a nanochannel, has drawn much attention, recently. Here, the ICR behavior of a pH-regulated nanochannel comprising two series connected cylindrical nanochannels of different radii is examined theoretically, focusing on the influences of the radii ratio, the length ratio, the bulk concentration, and the solution pH. The results of numerical simulation reveal that the rectification factor exhibits a local maximum with respect to both the radii ratio and the length ratio. The values of the radii ratio and the length ratio at which the local maximum in the rectification factor occur depend upon the level of the bulk salt concentration. The rectification factor also shows a local maximum as the solution pH varies. Among the factors examined, the solution pH influences the ICR behavior of the nanochannel most significantly.

Serum levels of 25-hydroxy vitamin D correlate with idiopathic benign paroxysmal positional vertigo.

Background: The present study aimed to evaluate serum 25-hydroxy vitamin D (25(OH) D) levels in Chinese patients with idiopathic benign paroxysmal positional vertigo (BPPV) and to investigate the possible relationship between the occurrence and recurrence of idiopathic BPPV and low 25(OH) D levels. Methods: Between 1 January 2017 and 31 May, 2018, consecutively older patients (age, older than 50 years) with idiopathic BPPV were recruited in the present study. For each patient, 2:1 sex and age matched healthy people were assigned as the control group. The influence of 25(OH) D levels on BPPV and recurrent BPPV were performed by binary logistic regression analysis. Results: In the present study, 174 patients with BPPV and 348 controls were included. The serum levels of 25(OH) D in those patients were lower than in those controls (P<0.001). One hundred eight patients were found to have vitamin D deficiency; thus, the prevalence was 62.1%, which was higher than that in the controls (42.8%). The data showed that patients with recurrent BPPV (N = 31) had lower serum levels of 25(OH) D compared with those who were not (11.2 ng/ml [interquartile range, 7.2-20.8 ng/ml] vs 18.7 ng/ml [14.2-24.8 ng/ml]). The regression analyses demonstrated that vitamin D deficiency was associated with BPPV and recurrent BPPV with an odds ratio of 2.15 (95% confidence interval [CI], 1.30-4.32; P=0.006) and 5.16 (95% CI, 1.00-34.12; P=0.05). Conclusion: Decreased serum levels of 25(OH)D were associated with the occurrence and recurrence of BPPV in a Chinese population, independent of other baseline markers.

Fluorescence depletion properties of insulin-gold nanoclusters.

Insulin-gold nanoclusters exhibit outstanding biocompatibility, photostability, and fluorescence quantum efficiency. However, they have never been used in superresolution microscopy, which requires nonlinear switching or saturation of fluorescence. Here we examine the fluorescence and stimulated emission depletion properties of gold nanoclusters. Their bleaching rate is very slow, demonstrating superior photostability. Surprisingly, however, the best depletion efficiency is less than 70%, whereas the depletion intensity requirement is much higher than the expectation from a simple two-level model. Fluorescence lifetime measurement revealed two distinct lifetime components, which indicate intersystem and reverse intersystem crossing during excitation. Based on population dynamic calculation, excellent agreement of the maximal depletion efficiency is found. Our work not only features the first examination of STED with metallic clusters, but also reveals the significance of molecular transition dynamics when considering a STED labeling.

The music listening preferences and habits of youths in Singapore and its relation to leisure noise-induced hearing loss

<p><b>INTRODUCTION</b>Noise-induced hearing loss (NIHL) is a preventable condition, and much has been done to protect workers from it. However, thus far, little attention has been given to leisure NIHL. The purpose of this study is to determine the possible music listening preferences and habits among young people in Singapore that may put them at risk of developing leisure NIHL.</p><p><b>METHODS</b>In our study, the proportion of participants exposed to > 85 dBA for eight hours a day (time-weighted average) was calculated by taking into account the daily number of hours spent listening to music and by determining the average sound pressure level at which music was listened to.</p><p><b>RESULTS</b>A total of 1,928 students were recruited from Temasek Polytechnic, Singapore. Of which, 16.4% of participants listened to portable music players with a time-weighted average of > 85 dBA for 8 hours. On average, we found that male students were more likely to listen to music at louder volumes than female students (p < 0.001). We also found that the Malay students in our study listened to louder music than the Chinese students (p < 0.001).</p><p><b>CONCLUSION</b>We found that up to one in six young persons in Singapore is at risk of developing leisure NIHL from music delivered via earphones. As additional risks due to exposure to leisure noise from other sources was not taken into account, the extent of the problem of leisure NIHL may be even greater. There is a compelling need for an effective leisure noise prevention program among young people in Singapore.</p>

Circulating MicroRNAs as potential risk biomarkers for hematoma enlargement after intracerebral hemorrhage.

BACKGROUND AND PURPOSE: MicroRNAs have recently been shown to regulate the downstream bioprocesses of intracerebral hemorrhage. The aim of this study was to investigate whether miRNAs can be used as biomarkers to predict secondary hematoma enlargement (HE) in patients with ICH. METHODS: Consecutively, 79 ICH patients admitted within 6 h of symptom onset and 30 healthy individuals were enrolled in this study. Whole-genome miRNA expression profiles were generated in 32 patients (HE/non-HE: 14/18). Representative differentially expressed miRNAs were measured in all cases (HE/non-HE: 30/49) and normal controls (n = 30) by real-time PCR. RESULTS: Thirty miRNAs showed differential expressions in the plasma samples from patients with HE as compared with the non-HE controls. Compared to the hierarchical cluster analysis with all probes on microarray, all patients were separated into two main branches with only four exceptions by 30 differentially expressed miRNAs, improving the overall accuracy from 47.62 to 77.78% in the HE and 72.73 to 100% in the non-HE group. Further support vector machine (SVM) test can discriminate the two groups with 100% accuracy with 10 differentially expressed miRNAs. CONCLUSIONS: We demonstrated that multiple miRNAs are differentially expressed in the plasma of ICH patients with or without HE and may serve as circulating biomarkers for predicting HE after ICH.

Obviously increasing incidence trend for males but stable pathological proportions for both genders: esophageal cancer in Zhongshan of China from 1970-2007.

OBJECTIVES: To analyze esophageal cancer incidence and pathological data of Zhongshan in China in 1970- 2007, and to provide scientific information for its prevention and control. METHODS: From Zhongshan Cancer Registry esophageal cancer incident and pathological data were obtained. Pathological proportions and trends were calculated and analyzed. RESULTS: Although there was a continuously and obviously increasing trend for male incidence rates in 1970-2007 in Zhongshan, squamous cell carcinoma (SCC) and adenocarcinoma (AD) incident proportions during 1990-2007 remained relatively stable. Moreover, SCC was the major pathological type, accounting for 70.6 percent of all new cases, while AD were relatively few and accounted for only 2.66 percent throughout the period. CONCLUSION: The male esophageal cancer incident pattern in Zhongshan in 1970- 2007 was quite different from most other domestic areas. The data suggest that etiological analysis should be enhanced for improved control in Zhongshan.

High-sensitivity C-reactive protein is a strong risk factor for death after acute ischemic stroke among Chinese.

BACKGROUND AND PURPOSE: Elevated plasma C-reactive protein (CRP) has been suggested as a risk factor for ischemic stroke (IS) and coronary ischemic disease. Evidence has shown that high-sensitivity CRP (hs-CRP) is related to a worsening prognosis after IS, but hs-CRP was rare in a large-sample study in a Chinese population. We investigated the associations between hs-CRP and outcome of Chinese patients after acute IS. METHODS: Seven hundred and forty-one consecutive acute IS patients (74.9% male, mean age 60.9 years), with baseline characteristics and hs-CRP measured within 24 h after hospitalization, were admitted in this study. We also prospectively followed up for clinical outcome and death 3 months after disease onset. hs-CRP was divided into two categories: hs-CRP >3 mg/L and hs-CRP ≤3 mg/L. Survival analysis using multivariable Cox regression was performed to analyze the association between hs-CRP and stroke outcomes after adjusting for potential confounding factors. RESULTS: Compared with low hs-CRP, patients with high hs-CRP (>3 mg/L) had a significantly higher rate of all-cause death (0.71% vs. 10.00%; P < 0.001) at 3 months after stroke onset. High hs-CRP was an independent risk factor for all-cause death (HR, 6.48; 95% CI, 1.41 to 29.8; P= 0.016), as well as history of atrial fibrillation (HR, 5.24; 95% CI, 1.83 to 15.0; P= 0.002), no statin therapy during hospitalization (HR, 4.56; 95% CI, 2.18 to 9.55; P < 0.001), high homocysteine (>15.1 mmol/L) (HR, 2.66; 95% CI, 1.26 to 5.60; P= 0.01); fasting glucose (>6.1 mmol/L) (HR, 9.14; 95% CI, 3.34 to 25.0; P < 0.001), NIHSS at admission (HR, 2.35; 95% CI, 1.35 to 4.09; P= 0.003) and history of coronary heart disease (CHD) (HR, 2.34; 95% CI, 1.06 to 5.17; P= 0.035). Kaplan-Meier survival curves showed a higher risk of death for patients with hs-CRP >3 mg/L (P= 0.016). CONCLUSION: Elevated plasma hs-CRP independently predicted risk of all-cause death within 3 months after acute IS in Chinese patients.

Noise-induced anomalous diffusion over a periodically modulated saddle.

We study analytically and numerically the anomalous diffusion across periodically modulated parabolic potential within Langevin and Fokker-Planck descriptions. We find that the probability of particles passing over the saddle is affected strikingly by the periodical modulation with average zero bias. Particularly, the initial phase plays an important role in the modulation effect. The effect of the correlation time of external Ornstein-Uhlenbeck noise on dynamical process is also discussed. A reduction in overpassing probability is observed due to finite correlation time.

[Three-dimensional reconstruction technique in gastrocnemius flap surgery: initial clinical application].

OBJECTIVE: To discuss the experience with three-dimensional reconstruction technique in initial clinical application in gastrocnemius muscle flap surgery. METHOD: From 2007 to 2008, 7 patients received gastrocnemius muscle flap surgeries to repair the wounds. Preoperative CT angiography or magnetic resonance imaging (MRI) was performed after injection of the contrast media for individualized three-dimensional gastrocnemius muscle flap reconstruction using Amira4.1 software. According to the size of the defect in the wound, individualized three-dimensional gastrocnemius muscle flap was designed and harvested from the posterior leg. RESULTS: Individualized three-dimensional reconstruction of the gastrocnemius flap was performed in 7 cases, and the reconstructed flaps clearly displayed the blood vessels, skin and the adjacent three-dimensional structures. In 6 cases the main perforating branched and trunk of the blood vessels in the designed flap were consistent with the surgical findings; in 1 case, the perforating branches failed to be clearly displayed in the designed flap, and surgical examination identified perforating branches with an average diameter of 0.5 mm (minimally 0.3 mm). The flaps survived in all the 7 cases. CONCLUSIONS: Three-dimensional reconstruction of the gastrocnemius flap based on the lower limb CT angiography or MRI allows three-dimensional observation of the anatomy of the flap and accurate marking of the extent of the flap to be harvested, therefore avoiding intraoperative injuries to the blood vessels to better survival of the flaps.

A new synthesis and an antiviral assessment of the 4'-fluoro derivative of 4'-deoxy-5'-noraristeromycin.

A synthetic route to (1S,2S,3R,5S)-3-(6-amino-9H-purin-9-yl)-5-fluorocyclopentane-1,2-diol (that is, the 4'-fluoro derivative of 4'-deoxy-5'-noraristeromycin, 3) is described via a fluorinated cyclopentanol, which is in contrast to existing schemes where fluorination occurred once the purine ring was present. Compound 3 was assayed versus a number of viruses. A favorable response was observed towards measles (IC(50) of 1.2 microg/mL in the neutral red assay and 14 microg/mL by the visual assay) but this was accompanied by cytotoxicity in the CV-1 host cells (21-36 microg/mL). Among the viruses unaffected by 3 were human cytomegalovirus and the poxviruses (vaccinia and cowpox), which are three viruses that were inhibited by the 4',4'-difluoro analog of 3 (that is, 2).