Structure-based improvement of the binding affinity and recognition specificity of peptide competitors to target pediatric IL-5R/IL-5 interaction by gluing halogen bonds at their complex interface.

Human interleukin-5 (IL-5) cytokine mediates the development of eosinophils and is involved in a variety of immune inflammatory responses that play a major role in the pathogenesis of childhood asthma, leukemia, and other pediatric allergic diseases. The immunomodulatory cytokine functions by binding to its cognate cell surface receptor IL-5R in a sheet-by-sheet manner, which can be conformationally mimicked and competitively disrupted by a double-stranded cyclic AF18748 peptide. In this study, we systematically examined the co-crystallized complex structure of human IL-5R with AF18748 peptide and rationally designed a halogen bond to glue at the protein-peptide complex interface by substituting the indole moiety of AF18748 Trp13 residue with a halogen atom (X = F, Cl, Br, or I). High-level theoretical calculations imparted presence of the halogen bond between the oxygen atom (O) of IL-5R Glu58 backbone and the halogen atom (X) of AF18748 Trp13 side chain. Experimental assays confirmed that the halogen bond can promote peptide binding moderately or considerably. More importantly, the halogen bond not only enhances peptide affinity to IL-5R, but also improves peptide selectivity for its cognate IL-5R over other noncognate IL-R proteins. As might be expected, the affinity and selectivity conferred by halogen bond increase consistently in the order: H < F < Cl < Br < I. Structural modeling revealed that the halogen bond plus its vicinal π-cation-π stacking co-define a ringed noncovalent system at the complex interface, which involves a synergistic effect to effectively improve the peptide binding potency and recognition specificity.

Stabilization of Uranium in Acid Ore Wastewater through Hydrothermal Mineralization-Induced Crystallization.

Uranium [U(VI)] mining activity resulted in the discharge of uranium containing acid wastewater. It is necessary for immobilizing the uranium from wastewater to avoid its environmental pollution. In this work, a novel hydrothermal mineralization strategy is proposed for uranium stabilization. Three reaction systems such as Mg3(PO4)2 + UO22+, Mg2+ + PO43- + UO22+, and Mg2+ + PO43- + Mg3(PO4)2 + UO22+ were designed to investigate the uranium mineralization and stabilization performance. The consumed molar quantities of magnesium and phosphate were calculated to understand the mineralization mechanisms. The molar ratios of Mg/U and P/U in the experimental results were in agreement with those of thermodynamic calculation in the presence of dissolved Mg2+ and PO43- under the hydrothermal process. The calculated saturated index indicated the facile crystallization of uranium into the saleeite and chernikovite through hydrothermal mineralization at the pH value of 5 and 473 K. Crystallization into saleeite and chernikovite contributed to uranium stabilization, resulting in the negligible leaching rate of 5% due to the high crystallinity of 97.23%. Thus, hydrothermal mineralization of uranium crystallization into saleeite and chernikovite was promising for uranium stabilization with long-term stability.

Impact of Chinese herbal medicine on sarcopenia in enhancing muscle mass, strength, and function: A systematic review and meta-analysis of randomized controlled trials.

Sarcopenia has become important to the public health with the increase in the aging population in society. However, the therapeutic effects of conventional approaches, including pharmacotherapy, exercise, and nutritional intervention, are far from satisfactory. Chinese herbal medicine is a new treatment format with interesting possibilities in sarcopenia has been widely practiced. The study aims to explore the effectiveness of Chinese herbal medicine in sarcopenia. We comprehensively searched the following electronic databases: Medline, EMBASE, APA PsycInfo, Cochrane Library, Web of Science, PubMed, and Chinese database from the establishment of the database to December 2022 (no language restrictions). Randomized controlled clinical studies on the use of Chinese herbal medicine in sarcopenia were selected in compliance with PRISMA guidelines. Review Manager and Stata were used for statistical analysis and the mean difference and standardized mean difference were adopted. Of 277 identified studies, 17 were eligible and included in our analysis (N = 1440 participants). The results showed that Chinese herbal medicine can improve total efficiency (RR = 1.29, 95% CI [1.21, 1.36], p < 0.00001) in sarcopenia and enhance muscle mass (SMD = 1.02, 95% CI [0.55, 1.50], p < 0.0001), and muscle strength measured by grip strength (SMD = 0.66, 95% CI [0.36, 0.96], p < 0.0001), measured by 60°/s knee extension peak TQ (MD = 5.63, 95% CI [-0.30, 11.57], p = 0.06) and muscle function measured by 6-meter walking speed (SMD = 1.34, 95% CI [0.60, 2.08], p = 0.0004), measured by the short physical performance battery of 1.50%, 95% CI (1.05, 1.95), measured by the EuroQoL 5-dimension of (SMD = 0.27, 95% CI [-0.10, 0.65], p = 0.16), suggesting that Chinese herbal medicine alone or combined with conventional treatment has ameliorating effect on sarcopenia. Chinese herbal medicine is a potential therapeutic strategy in sarcopenia. The funnel plot and Egger's test indicated publication bias. To confirm our conclusions, further high-quality studies should be conducted.

Bilayer LDPC Codes Combined with Perturbed Decoding for MLC NAND Flash Memory.

This paper presents a coding scheme based on bilayer low-density parity-check (LDPC) codes for multi-level cell (MLC) NAND flash memory. The main feature of the proposed scheme is that it exploits the asymmetric properties of an MLC flash channel and stores the extra parity-check bits in the lower page, which are activated only after the decoding failure of the upper page. To further improve the performance of the error correction, a perturbation process based on the genetic algorithm (GA) is incorporated into the decoding process of the proposed coding scheme, which can convert uncorrectable read sequences into error-correctable regions of the corresponding decoding space by introducing GA-trained noises. The perturbation decoding process is particularly efficient at low program-and-erase (P/E) cycle regions. The simulation results suggest that the proposed bilayer LDPC coding scheme can extend the lifetime of MLC NAND flash memory up to 10,000 P/E cycles. The proposed scheme can achieve a better balance between performance and complexity than traditional single LDPC coding schemes. All of these findings indicate that the proposed coding scheme is suitable for practical purposes in MLC NAND flash memory.

The impact of the COVID-19 pandemic on the prevalence and genotype distribution of HPV infection in Beijing, China.

Human papillomavirus (HPV) is one of the most common sexually transmitted infections nationwide. The COVID-19 pandemic has greatly influenced on the HPV prevention project. The objective of this study was to examine the influence of the pandemic on HPV prevalence and genotype distribution in Beijing, China. A total of 44 401 genital swabs were obtained from outpatients at Peking Union Medical College Hospital during two distinct periods: the prepandemic stage from January 2017 to December 2019 and the pandemic stage from January 2020 to December 2022. During the prepandemic and pandemic stages, a total of 33 531 and 10 870 swabs were respectively collected. Fifteen high-risk HPV (HR-HPV) DNA type and a combination of two low-risk (LR-HPV) types (6/11) of genital swabs were detected to compare the HPV infection rates and genotype distributions in two stages. The results showed that the pandemic period witnessed a decrease in the overall HPV infection rate from 33.43% (11 245/33 531) to 29.43% (5527/18 780) compared to the prepandemic. There were statistically significant differences in infection rates between females and males (p < 0.05). Single infection was the predominant type while multiple infection was more prevalent in males than females in both prepandemic and pandemic periods. HR-HPV infection constituted the majority of infections and cannot be disregarded. The distribution of HR-HPV genotypes exhibited little variation before and after the outbreak, but there were some differences between females and males. HPV 16, 52, 58, 56, and 66 were the most commonly detected genotypes in females, whereas HPV 16, 52, 51, 58, and 18 were frequently detected in males. Additionally, HPV 6/11 exhibited a higher prevalence in males than in females. Notably, the age group of 31-40 years old exhibited the highest prevalence of HPV and the lowest infection rate was detected among individuals aged ≤20 years (p < 0.05), which remained relatively consistent before and during the pandemic. These findings underscore the importance of monitoring the trend of HPV epidemic and offer valuable insights for the prevention, treatment, and scientific investigation of HPV in the post-COVID-19 era.

Laguerre Gaussian mode holography and its application in optical encryption.

Holography provides an approach to reconstructing both intensity and phase information, and has many applications for microscopic imaging, optical security, and data storage. Recently, the azimuthal Laguerre-Gaussian (LG) mode index, orbital angular momentum (OAM), has been implemented in holography technologies as an independent degree of freedom for high-security encryption. The radial index (RI) of LG mode, however, has not been implemented as an information carrier in holography. Here we propose and demonstrate the RI holography by using strong RI selectivity in the spatial-frequency domain. Furthermore, the LG holography is realized theoretically and experimentally with the (RI, OAM) spanning from (1, -15) to (7, 15), which leads to a 26bit LG-multiplexing hologram for high-security optical encryption. Based on LG holography, a high-capacity holographic information system can be constructed. In our experiments, a LG-multiplexing holography with a span of 217 independent LG channels has been realized, which is inaccessible at present for the OAM holography.

High-Dimensional Entanglement-Enabled Holography.

As an important imaging technique, holography has been realized with different physical dimensions of light, including polarization, wavelength, and time. Recently, quantum holography has been demonstrated by utilizing polarization entangled state with the advantages of high robustness and enhanced spatial resolution, comparing with classical holography. However, the polarization is only a two-dimensional degree of freedom, which greatly limits the capacity of quantum holography. Here, we propose a method to realize high-dimensional quantum holography by using high-dimensional orbital angular momentum (OAM) entanglement. A high-capacity OAM-encoded quantum holographic system can be obtained by multiplexing a wide range of OAM-dependent holographic images. Proof-of-principle experiments with four- and six-dimensional OAM entangled states have been implemented and verify the feasibility of our idea. Our experimental results also demonstrate that the high-dimensional quantum holography shows a high robustness to classical noise. What is more, the level of security of the holographic imaging encryption system can be greatly improved in our high-dimensional quantum holography.

Prevalence of Ureaplasma species among patients at a tertiary hospital in China: a 10-year retrospective study from 2013 to 2022.

BACKGROUND: Ureaplasma species are common pathogens of the urogenital tract and can cause a range of diseases. Unfortunately, there is still a scarcity of large-scale and cross-sectional studies on the prevalence of Ureaplasma species in China to clarify their epidemic patterns. METHODS: This study retrospectively analyzed the data of 18667 patients who visited Peking Union Medical College Hospital for showing various symptoms of (suspected) Ureaplasma species infection during the period 2013-2022. The overall prevalence of Ureaplasma species was calculated, and subgroup analyses were conducted in view of gender, age, specimen types, and diagnosis in every year within the period studied. Furthermore, previous literature that reported on the prevalence of Ureaplasma species in various regions of China was searched and summarized. RESULTS: The overall positive rate of Ureaplasma species in this study reached 42.1% (7861/18667). Specifically, the prevalence of Ureaplasma species was significantly higher in female patients, while the highest detection rate was found in the 21-50 age group. From 2013 to 2022, there were no significant differences in positive rates of Ureaplasma species among years. However, the detection rate of Ureaplasma species was decreased in COVID-19 period (2020-2022) compared to pre-COVID-19 period (2017-2019). In view of the distribution of patients, outpatients predominated, but the detection rate was lower than inpatients. Urine was the most common specimen type, while cervical swabs had the highest detection rate of Ureaplasma species. When grouped by diagnosis, the highest positive rate of Ureaplasma species was seen in patients with adverse pregnancy outcomes and the lowest rate in patients with prostate disease. The previous literature, although heterogeneous, collectively suggested a high prevalence of Ureaplasma species in China. CONCLUSIONS: Our study has shown that Ureaplasma species have reached a significant prevalence in China and demands adequate attention.

Histone deacetylase inhibitor panobinostat in combination with rapamycin confers enhanced efficacy against triple-negative breast cancer.

Triple-negative breast cancer (TNBC) accounts for about 15% of diagnosed breast cancer patients, which has a poor survival outcome owing to a lack of effective therapies. This study aimed to explore the in vitro and in vivo efficiency of histone deacetylase (HDAC) inhibitor panobinostat (PANO) in combination with mTOR inhibitor rapamycin (RAPA) against TNBC. TNBC cells were treated with PANO, RAPA alone or the combination of drugs, then cell growth and apoptosis were evaluated by CCK-8, colony formation and flow cytometry. Cell migration and invasion were detected by wound healing assay and transwell assay, respectively. ROS production was detected by DCFH-DA staining. Western blotting was performed to detect protein levels. In vivo tumor growth was assessed in nude mice. The expression of cleaved caspase-3 and Ki-67 in tumor tissues was detected by immunofluorescence staining. H&E staining was conducted to observe the pathological changes in heart, liver, and kidney tissues. The combination of PANO and RAPA exerted a stronger role in repressing growth, migration, invasion, and inducing apoptosis of TNBC cells compared with monotherapy. Furthermore, this combination presented a more effective anti-cancer efficacy than a single treatment in the xenograft model without apparent toxic side effects. Importantly, mechanistic studies indicated that PANO and RAPA combination led to ROS overproduction, which subsequently activated endoplasmic reticulum stress. Conclusion: PANO in combination with RAPA exhibits enhanced efficacy against TNBC, which may be considered a promising therapeutic candidate.

Exploring the bidirectional relationship between pain and mental disorders: a comprehensive Mendelian randomization study.

BACKGROUND: The close relationship between pain and mental health problems is well-known, and psychological intervention can provide an effective alternative to medication-based pain relief. However, previous studies on the connection between pain and psychological problems, the findings thus far have been inconclusive, limiting the potential for translating psychological interventions into clinical practice. To complement the gap, this study utilized genetic data and Mendelian randomization (MR) to examine the potential relationship between pain in different parts and common mental disorders. METHODS: Based on the instrumental variables selected from the Genome-wide association study summary statistics of localized pain and mental disorders, we conducted bidirectional two-sample MR analyses to infer bidirectional causal associations between pain and mental disorders. The inverse-variance weighted MR method and MR-Egger were used as the primary statistical method according to the horizontal pleiotropy and heterogeneity level. We reported the odds ratio to infer the causal effect between pain and mental disorders. F statistic was calculated to measure the statistical efficacy of the analyses. RESULTS: Insomnia is causally related to the genetic susceptibility of multisite pain including head (OR = 1.09, 95% CI: 1.06-1.12), neck/shoulder (OR = 1.12, 95% CI: 1.07-1.16), back (OR = 1.12, 95% CI: 1.07-1.18) and hip (OR = 1.08, 95% CI: 1.05-1.10). Reversely, headache (OR = 1.14, 95% CI: 1.05-1.24), neck/shoulder pain (OR = 1.95, 95% CI: 1.03-3.68), back pain (OR = 1.40, 95% CI: 1.22-1.60), and hip pain (OR = 2.29, 95% CI: 1.18-4.45) promote the genetic liability of insomnia. Depression is strongly associated with the predisposition of multisite pain including headache (OR = 1.28, 95% CI: 1.08-1.52), neck/shoulder pain (OR = 1.32, 95% CI: 1.16-1.50), back pain (OR = 1.35, 95% CI: 1.10-1.66) and stomach/abdominal pain (OR = 1.14, 95% CI: 1.05-1.25), while headache (OR = 1.06, 95% CI: 1.03-1.08), neck/shoulder (OR = 1.09, 95% CI: 1.01-1.17), back (OR = 1.08, 95% CI: 1.03-1.14), and stomach/abdominal pain (OR = 1.19, 95% CI: 1.11-1.26) are predisposing factors for depression. Additionally, insomnia is associated with the predisposition of facial, stomach/abdominal, and knee pain, anxiety was associated with the predisposition of neck/shoulder and back pain, while the susceptibilities of hip and facial pain are influenced by depression, but these associations were unidirectional. CONCLUSIONS: Our results enhance the understanding of the complex interplay between pain and mental health and highlight the importance of a holistic approach to pain management that addresses both physical and psychological factors.

Channel Modeling and Quantization Design for 3D NAND Flash Memory.

As the technology scales down, two-dimensional (2D) NAND flash memory has reached its bottleneck. Three-dimensional (3D) NAND flash memory was proposed to further increase the storage capacity by vertically stacking multiple layers. However, the new architecture of 3D flash memory leads to new sources of errors, which severely affects the reliability of the system. In this paper, for the first time, we derive the channel probability density function of 3D NAND flash memory by taking major sources of errors. Based on the derived channel probability density function, the mutual information (MI) for 3D flash memory with multiple layers is derived and used as a metric to design the quantization. Specifically, we propose a dynamic programming algorithm to jointly optimize read-voltage thresholds for all layers by maximizing the MI (MMI). To further reduce the complexity, we develop an MI derivative (MID)-based method to obtain read-voltage thresholds for hard-decision decoding (HDD) of error correction codes (ECCs). Simulation results show that the performance with jointly optimized read-voltage thresholds can closely approach that with read-voltage thresholds optimized for each layer, with much less read latency. Moreover, the MID-based MMI quantizer almost achieves the optimal performance for HDD of ECCs.

Transcriptome profiling of microRNAs reveals potential mechanisms of manual therapy alleviating neuropathic pain through microRNA-547-3p-mediated Map4k4/NF-κb signaling pathway.

BACKGROUND: Local neuroinflammation secondary to spinal nerve compression in lumbar disk herniation (LDH) is a key driver contributing to neuropathic pain. Manual therapy (MT), a widely used nonsurgical therapy, can relieve LDH-mediated pain by reducing inflammation. MT has attracted extensive attention; however, its mechanism remains poorly understood. MicroRNAs (miRNAs) are important regulators of pain signaling transduction, but are rarely reported in the chronic compression of dorsal root ganglia (CCD) model, and further investigation is needed to decipher whether they mediate anti-inflammatory and analgesic effects of MT. METHODS: We used a combination of in vivo behavioral and molecular techniques to study MT intervention mechanisms. Neuropathic pain was induced in a CCD rat model and MT intervention was performed according to standard procedures. Enzyme-linked immunosorbent assay (ELISA) was used to detect inflammatory cytokine levels in dorsal root ganglia (DRG). Small RNA sequencing, immunofluorescence, Western blot, and qRT-PCR were performed to screen miRNAs and their target genes and determine core factors in the pathway possibly regulated by miRNA-mediated target gene in DRG of MT-treated CCD rats. RESULTS: Compared with naive rats, small RNA sequencing detected 22 differentially expressed miRNAs in DRG of CCD rats, and compared with CCD rats, MT-treated rats presented 19 differentially expressed miRNAs, which were functionally associated with nerve injury and inflammation. Among these, miR-547-3p was screened as a key miRNA mediating neuroinflammation and participating in neuropathic pain. We confirmed in vitro that its function is achieved by directly regulating its target gene Map4k4. Intrathecal injection of miR-547-3p agomir or MT intervention significantly reduced Map4k4 expression and the expression and phosphorylation of IκBα and p65 in the NF-κB pathway, thus reducing the inflammatory cytokine levels and exerting an analgesic effect, whereas intrathecal injection of miR-547-3p antagomir led to opposite effects. CONCLUSIONS: In rats, CCD-induced neuropathic pain leads to variation in miRNA expression in DRG, and MT can intervene the transcription and translation of inflammation-related genes through miRNAs to improve neuroinflammation and alleviate neuropathic pain. MiR-547-3p may be a key target of MT for anti-inflammatory and analgesia effects, which is achieved by mediating the Map4k4/NF-κB pathway to regulate downstream inflammatory cytokines.

Clinical impact of the PAI-1 4G/5G polymorphism in Chinese patients with venous thromboembolism.

BACKGROUND: Venous thromboembolism (VTE) is a life-threatening cardiovascular syndrome that characterized by the imbalance of hemostasis and thrombosis and the formation of thrombi in the blood vessels. The aim of this study was to elucidate the clinical impact of the PAI-1 4G/5G polymorphism in Chinese patients with VTE. METHODS: A total of 169 subjects (89 VTE, 10 hyperbilirubinemia, 10 hyperlipidemia and 60 healthy controls) were recruited at Peking Union Medical College Hospital. The accuracy of the TaqMan-MGB RT-PCR method for detecting F5 G1691A (FVL) and PAI-1 4G/5G polymorphisms was evaluated by using sequencing method as the gold standard. Besides, the association of the PAI-1 4G/5G polymorphism with susceptibility, treatment efficacy and recurrence status of VTE in Chinese population were explored. Eventually, the plasma PAI-1 antigen levels and PAI-1 4G/5G polymorphisms were determined on additional 64 subjects (32 VTE and 32 healthy controls) simultaneously. RESULTS: The TaqMan-MGB RT-PCR method was proven to be highly accurate in determining the FVL and PAI-1 4G/5G polymorphisms without interference from bilirubin and lipids in the samples. No obvious correlation of the PAI-1 4G/5G polymorphism with VTE was observed in our study by using five genetic models (allele, genotype, dominant, recessive and additive). Additionally, we also observed that individuals with the 4G/5G genotype had lower neutrophil counts and neutrophil-to-lymphocyte ratio (NLR) than the 5G/5G genotype. Furthermore, we found that the patients with the 5G/5G genotype were more likely to achieve complete recanalization compared to the 4G/4G genotype. In addition, individuals carrying the 5G/5G genotype were more likely to develop a recurrence-free status as compared to individuals with the 4G/4G or 4G/5G genotypes. PAI-1 antigen levels in the VTE group were significantly higher than those in the HC group. However, there was no significant difference in the antigen levels of PAI-1 among subjects carrying various genotypes in the VTE group or HC group. CONCLUSION: The PAI-1 4G/5G polymorphism has potential value in assessing the prognosis of Chinese patients with VTE. Our study has laid the foundation for the application of PAI-1 4G/5G polymorphism in the personalized management and monitoring of patients with VTE.

Calpain inhibitors inhibit mitochondrial calpain activity to ameliorate apoptosis of cocultured myoblast.

Cancer cachexia is a fatal syndrome associated with muscle regeneration disability. Tumor factors induce the apoptosis of myoblasts to impair the regeneration of skeletal muscle. Cancer cachectic myoblast apoptosis is associated with mitochondria injury. It has been reported that activated mitochondrial calpain caused mitochondria injury in mouse cardiomyocytes and pulmonary smooth muscle. We wondered if mitochondrial calpains exist in skeletal myoblast and their potential role in myoblast apoptosis of cancer cachexia. We used a transwell to build a novel myoblast-carcinoma cell coculture model to simulate the cancer cachexia environment in vitro. Calpain inhibitors, calpastatin (CAST) and calpeptin (CAPT), were used during coculture. We found for the first time that two calpains (calpain-1 and calpain-2) and CAST were present in the mitochondria of myoblast. The activation of mitochondrial calpain decreased mitochondrial complex I activity, promoted mitochondrial permeability transition pore opening, and impaired mitochondrial membrane potential in myoblast during coculture, which induced myoblasts apoptosis. CAST and CAPT protected myoblasts from apoptosis by inhibiting mitochondrial calpain activity, which may attenuate or even reverse cancer cachectic muscle atrophy by improving muscle regeneration ability. Our study provides a new perspective for understanding the mechanism of cancer cachexia, and will further contribute to treat cancer cachexia by focusing on the mitochondrial calpain activity.

Delphian lymph node metastasis is a novel indicator of tumor aggressiveness and poor prognosis in papillary thyroid cancer.

BACKGROUND AND OBJECTIVES: Although the significance of Delphian lymph nodes (DLNs) in patients with papillary thyroid carcinoma (PTC) has been reported, all studies have been based on a small sample size and lack a direct statement concerning prognosis. METHODS: A total of 904 consecutive patients were enrolled in the current study, and all patients were divided into two groups (DLN-positive and DLN-negative) according to the presence of DLN metastasis. RESULTS: DLN was detected in 687 patients (76.0%), and 123 (17.9%) had DLN metastasis. Compared to those in the DLN-negative group, the proportion of other central lymph node (CLN) metastases, mean number of metastatic CLNs, and mean metastatic CLN ratio were higher in the DLN-positive group (86.2 vs. 50.2%, 6.70 ± 5.19 vs. 1.60 ± 2.37, and 0.54 ± 0.25 vs. 0.18 ± 0.26, respectively; p < .001). The same phenomena were observed in the metastatic lateral lymph nodes (LLNs) between the DLN-positive and DLN-negative groups (52.0 vs. 15.4%, 7.28 ± 6.08 vs. 3.38 ± 3.73, and 0.23 ± 0.15 vs. 0.13 ± 0.12, respectively; p < .001). Patients in the DLN-positive group had shorter LLN metastasis-free survival and distant metastasis-free survival than patients in the DLN-negative group (93.5% vs. 98.6% and 95.9% vs. 98.8%, respectively, p < .05). CONCLUSIONS: DLN metastasis in PTC is associated with tumor aggressiveness and a poor prognosis.

NOD2 induces VCAM-1 and ET-1 gene expression via NF-κB in human umbilical vein endothelial cells with muramyl dipeptide stimulation.

OBJECTIVES: Endothelial dysfunction is involved in various aspects of vascular biology and different stages of cardiovascular diseases (CVDs). Nucleotide-binding oligomerization domain-containing protein (NOD) 2, a pivotal innate immune receptor for muramyl dipeptide (MDP), has been reported to be a central regulator in CVDs. Previously, we reported that NOD2 played a leading role in MDP-triggered oxidative stress in endothelial cells (ECs). However, whether NOD2 participates in the regulatory mechanism of vascular cell adhesion molecule­1 (VCAM-1) and endothelin­1 (ET-1) expression was not elucidated. METHODS: Human umbilical vein endothelial cells (HUVECs) were stimulated with MDP for 12 h. mRNA expression of VCAM­1 and ET­1 was detected using real time polymerase chain reaction (PCR). Scrambled control small interfering RNA (siRNA) and NOD2 siRNA were transfected into HUVECs using Lipofectamine 2000 reagent (Invitrogen, Waltham, MA, USA). Furthermore, pyrrolidine dithiocarbamate was adopted to investigate the effect of nuclear factor κB (NF-κB) on NOD2-mediated VCAM­1 and ET­1 gene expression in MDP-treated HUVECs. RESULTS: Data showed that MDP significantly increased VCAM­1 and ET­1 mRNA expression, which was dependent on NOD2. In addition, NF-κB inhibition suppressed NOD2-mediated gene expression of VCAM­1 and ET­1. CONCLUSION: Collectively, we confirmed NOD2 aggravated VCAM­1 and ET­1 gene expression through NF-κB in HUVECs treated with MDP.

Electrochemically active sites inside crystalline porous materials for energy storage and conversion.

The design and development of crystalline porous materials (CPMs), including metal-organic frameworks (MOFs) and covalent-organic frameworks (COFs), have been subjects of extensive study due to their regular crystalline lattices and well-defined pore structures. In recent times, an enormous amount of research effort has gone into using CPMs as sacrificial templates to fabricate electrochemically functional materials. The inherently electrochemically active sites inside CPMs are notably abundant and being explored with respect to electrochemical reactions. In this review, electrochemically active sites and the space around them (metal ions, ligands, crystal structures, pores, and morphologies) inside CPMs are the focus and recent progress in the fields of metal-ion batteries, metal-air batteries, water splitting, and other related electrochemical devices has been summarized. Overall, this review provides guidance on the preparation of electroactive CPMs via rational design and modulation of active sites such as redox-active metal clusters and organic ligands, and the space around the electrochemically active sites, and their applications in electrochemical energy storage and conversion systems.

Theoretical analysis based on mirror symmetry for tightly focused vector optical fields.

A theoretical analysis based on mirror symmetry is proposed to analyze and predict the symmetry in intensity, phase and polarization distributions of the tightly focused vector optical field (VOF). We extend the analysis to more cases including more complicated polarization states and weak focusing cases. We further show the symmetric tightly focused fields of the eccentric cylindrical VOF and the redesigned VOF with a radially variant polarization state, which are achieved by redesigning the polarization state of the incident VOF based on the symmetry analysis. We also take the laser fabrication as an example to further show how to apply this symmetry analysis in a specific application area. Such a theoretical analysis can improve the calculation efficiency, provide new insights into the tight focusing process and offer a convenient way to engineer the field distributions in the focal plane, which may have potential applications in areas needing flexibly controllable tightly focused fields, such as laser fabrication, optical trapping, and optical storage.

Pancharatnam-Berry geometric phase memory based on spontaneous parametric down-conversion.

Phase memory is an effect in which the interaction between a coherent pump beam and a nonlinear crystal generates photon pairs via the spontaneous parametric down-conversion process, then the down-converted photons (signal and idler) can carry the phase information of the pump beam. There has been much research on the memory of the dynamic phase so far; however, there is no report on the memory of non-dynamic phase, to the best of our knowledge. Here we acquire a Pancharatnam-Berry (PB) geometric phase in a physical system when light travels along a trajectory in polarization-state space. Induced coherence occurs in a cascaded scheme composed of two nonlinear crystals, when the idler photons in both crystals are aligned to be indistinguishable. A NOON ($N\; = \;{2}$N=2) state is established when blocking the two idler photons. We explore the PB geometric phase memory of the NOON state and induced coherence. We find that the first-order interference of the two-photon state or signal photons can be controlled by introducing the PB geometric phase to the pump light. This may facilitate precise control of the phase of the down-converted photons.

miR-101-3p induces vascular endothelial cell dysfunction by targeting tet methylcytosine dioxygenase 2.

Endothelial cell (EC) dysfunction represents an early key event in atherosclerosis. Recently, MicroRNAs have been demonstrated to regulate EC function. miR-101-3p has been discovered to regulate cell apoptosis and proliferation in cardiovascular diseases. Therefore, the aim of the current study was to clarify whether miR-101-3p regulates the dysfunction of vascular endothelial cells. In this study, the transfection of human umbilical vein endothelial cells (HUVECs) with miR-101-3p mimic induced reactive oxygen species (ROS) production, EC dysfunction, and activated nuclear factor-κB (NF-κB), whereas transfection with miR-101-3p inhibitor alleviated these events. The antioxidant N-acetylcysteine alleviated miR-101-3p-induced EC dysfunction. Moreover, we observed that miR-101-3p inhibited the expression of tet methylcytosine dioxygenase 2 (TET2) at the posttranscriptional level, resulting in increased ROS production and activated NF-κB. TET2 overexpression inhibited ROS production, EC dysfunction, and NF-κB activation in miR-101-3p-transfected HUVECs. These results indicate that miR-101-3p induces EC dysfunction by targeting TET2, which regulates ROS production, EC dysfunction, and NF-κB activation. Taken together, our current study reveals a novel pathway associated with EC dysfunction. The modulation of miR-101-3p and TET2 expression levels may serve as a potential target for therapeutic strategies for atherosclerosis.