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Abstract The gas vesicle (GV) is like a hollow nanoparticle consisting of an internal gas and a protein shell, which mainly consists of hydrophobic gas vesicle protein A (GvpA) and GvpC attached to the surface. GVs, first discovered in cyanobacteria, are mainly produced by photosynthetic bacteria (PSB) and halophilic archaea. After being modified and engineered, GVs can be utilized as contrast agents, delivery carriers, and immunological boosters for disease prevention, diagnosis, and treatment with good results due to their tiny size, strong stability and non-toxicity advantages. Many diagnostic and therapeutic approaches based on GV are currently under development. In this review, we discuss the source, function, physical and chemical properties of GV, focus on the current application progress of GV, and put forward the possible application prospect and development direction of GV in the future.

In the field of super-resolution reconstruction, generative adversarial networks are able to generate textures that are more in line with the perception of the human eyes, but low-resolution images often encounter information loss and edge blurring problems in the process of reconstruction. In order to solve this problem, this article proposed an image super-resolution reconstruction model based on an enhanced attention mechanism and gradient correlation loss, which can better focus on important details in low-resolution images, thus improving the quality of reconstructed images. Firstly, an enhanced attention mechanism is proposed and incorporated into the generator model as a way to reduce the amount of information loss during image feature extraction and retain more image details. Furthermore, this paper proposed a gradient correlation loss function to maximize the correlation between the gradient of the generated image and the gradient of the original image. Thus, the generated image is more realistic and maintains a consistent edge structure. Finally, the experimental results on the standard dataset show that compared with other representative algorithms, the proposed algorithm has achieved some improvement in PSNR, SSIM, and LPIPS, which can verify the effectiveness of the algorithm.

Abstract Objective To investigate and evaluate the biomechanical behaviour of a novel bone cement screw in the minimally invasive treatment of Kummell's disease (KD) by finite element (FE) analysis. Methods A validated finite element model of healthy adult thoracolumbar vertebrae T12-L2 was given the osteoporotic material properties and the part of the middle bone tissue of the L1 vertebral body was removed to make it wedge-shaped. Based on these, FE model of KD was established. The FE model of KD was repaired and treated with three options: pure percutaneous vertebroplasty (Model A), novel unilateral cement screw placement (Model B), novel bilateral cement screw placement (Model C). Range of motion (ROM), maximum Von-Mises stress of T12 inferior endplate and bone cement, relative displacement of bone cement, and stress distribution of bone cement screws of three postoperative models and intact model in flexion and extension, as well as lateral bending and rotation were analyzed and compared. Results The relative displacements of bone cement of Model B and C were similar in all actions studied, and both were smaller than that of Model A. The minimum value of relative displacement of bone cement is 0.0733 mm in the right axial rotation of Model B. The maximum Von-Mises stress in T12 lower endplate and bone cement was in Model C. The maximum Von-Mises stress of bone cement screws in Model C was less than that in Model B, and it was the most substantial in right axial rotation, which is 34%. There was no substantial difference in ROM of the three models. Conclusion The novel bone cement screw can effectively reduce the relative displacement of bone cement by improving the stability of local cement. Among them, novel unilateral cement screw placement can obtain better fixation effect, and the impact on the biomechanical environment of vertebral body is less than that of novel bilateral cement screw placement, which provides a reference for minimally invasive treatment of KD in clinical practice.

ABSTRACTHuman metapneumovirus (HMPV) is a primary cause of acute respiratory infection, yet there are no approved vaccines or antiviral therapies for HMPV. Early host responses to HMPV are poorly characterized, and further understanding could identify important antiviral pathways. Type III interferon (IFN-λ) displays potent antiviral activity against respiratory viruses and is being investigated for therapeutic use. However, its role in HMPV infection remains largely unknown. Here, we show that IFN-λ is highly upregulated during HMPV infection in vitro in human and mouse airway epithelial cells and in vivo in mice. We found through several immunological and molecular assays that type II alveolar cells are the primary producers of IFN-λ. Using mouse models, we show that IFN-λ limits lung HMPV replication and restricts virus spread from upper to lower airways but does not contribute to clinical disease. Moreover, we show that IFN-λ signaling is predominantly mediated by CD45- non-immune cells. Mice lacking IFN-λ signaling showed diminished loss of ciliated epithelial cells and decreased recruitment of lung macrophages in early HMPV infection along with higher inflammatory cytokine and interferon-stimulated gene expression, suggesting that IFN-λ may maintain immunomodulatory responses. Administration of IFN-λ for prophylaxis or post-infection treatment in mice reduced viral load without inflammation-driven weight loss or clinical disease. These data offer clinical promise for IFN-λ in HMPV treatment.IMPORTANCEHuman metapneumovirus (HMPV) is a common respiratory pathogen and often contributes to severe disease, particularly in children, immunocompromised people, and the elderly. There are currently no licensed HMPV antiviral treatments or vaccines. Here, we report novel roles of host factor IFN-λ in HMPV disease that highlight therapeutic potential. We show that IFN-λ promotes lung antiviral responses by restricting lung HMPV replication and spread from upper to lower airways but does so without inducing lung immunopathology. Our data uncover recruitment of lung macrophages, regulation of ciliated epithelial cells, and modulation of inflammatory cytokines and interferon-stimulated genes as likely contributors. Moreover, we found these roles to be distinct and non-redundant, as they are not observed with knockout of, or treatment with, type I IFN. These data elucidate unique antiviral functions of IFN-λ and suggest IFN-λ augmentation as a promising therapeutic for treating HMPV disease and promoting effective vaccine responses.

With the changing demands imposed on forests by human beings, optimizing forest management to fully utilize their multifunctionality has become a priority. Reasonable forest management measures can maintain stable forest ecosystems that fully coordinate the balance between ecological, societal, and economic aspects. As planted forests are the main application scenario of forest management worldwide, it is of great importance to understand the trade-offs between ecosystem functions and their dynamic changes in planted forests. This paper investigates the effects of different management measures on the ecosystem function of Pinus massoniana plantation forests in the subtropics. It examines four different management measures and explores how they impact multiple ecosystem function indexes and the trade-offs between ecosystem functions during forest restoration. The different management measures effectively promoted the studied ecosystem functions, with higher annual growth rates of the integrated functional indices for timber production, carbon sequestration, and biodiversity compared to the control. Over time, the ecosystem function interactions under the different management measures alternated between trade-offs and synergistic. Only the stand with a 65% harvesting intensity and replanting of various native broadleaf species was able to sustain the synergistic relationships among ecosystem functions, and the dominant function trended toward biodiversity. These observations of dynamic changes and interactions in ecosystem functions of Pinus massoniana plantation forests under various management measures will serve as a valuable reference for the sustainable management of these forests in subtropical regions.

Modifications of mRNA, especially methylation of adenosine, have recently drawn much attention. The much rarer modification, 5-hydroxymethylation of cytosine (5hmC), is not well understood and is the subject of this study. Vertebrate Tet proteins are 5-methylcytosine (5mC) hydroxylases and catalyze the transition of 5mC to 5hmC in DNA. These enzymes have recently been shown to have the same function in messenger RNAs in both vertebrates and in Drosophila. The Tet gene is essential in Drosophila as Tet knock-out animals do not reach adulthood. We describe the identification of Tet-target genes in the embryo and larval brain by mapping one, Tet DNA-binding sites throughout the genome and two, the Tet-dependent 5hmrC modifications transcriptome-wide. 5hmrC modifications are distributed along the entire transcript, while Tet DNA-binding sites are preferentially located at the promoter where they overlap with histone H3K4me3 peaks. The identified mRNAs are preferentially involved in neuron and axon development and Tet knock-out led to a reduction of 5hmrC marks on specific mRNAs. Among the Tet-target genes were the robo2 receptor and its slit ligand that function in axon guidance in Drosophila and in vertebrates. Tet knock-out embryos show overlapping phenotypes with robo2 and both Robo2 and Slit protein levels were markedly reduced in Tet KO larval brains. Our results establish a role for Tet-dependent 5hmrC in facilitating the translation of modified mRNAs primarily in cells of the nervous system.

Abstract Background Although previous studies have suggested a close association between gut microbiota (GM) and intervertebral disc degeneration (IVDD), the causal relationship between them remains unclear. Hence, we thoroughly investigate their causal relationship by means of a two-sample Mendelian randomization (MR) study, aiming to determine the impact of gut microbiota on the risk of developing intervertebral disc degeneration. Methods Summary data from genome-wide association studies of GM (the MiBioGen) and IVDD (the FinnGen biobank) have been acquired. The inverse variance weighted (IVW) method was utilized as the primary MR analysis approach. Weighted median, MR-Egger regression, weighted mode, and simple mode were used as supplements. The Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) and MR-Egger regression were performed to assess horizontal pleiotropy. Cochran's Q test evaluated heterogeneity. Leave-one-out sensitivity analysis was further conducted to determine the reliability of the causal relationship. A reverse MR analysis was conducted to assess potential reverse causation. Results We identified nine gut microbial taxa that were causally associated with IVDD (P 0.05). Additionally, both the MR-Egger intercept test and the MR-PRESSO global test revealed that our results were not influenced by horizontal pleiotropy (P > 0.05). Furthermore, the leave-one-out analysis substantiated the reliability of the causal relationship. In the reverse analysis, no evidence was found to suggest that IVDD has an impact on the gut microbiota. Conclusion Our results validate the potential causal impact of particular GM taxa on IVDD, thus providing fresh insights into the gut microbiota-mediated mechanism of IVDD and laying the groundwork for further research into targeted preventive measures.

Abstract Background Lower respiratory infections are a leading cause of severe morbidity and mortality among older adults. Despite ubiquitous exposure to common respiratory pathogens throughout life and near universal seropositivity, antibodies fail to effectively protect the elderly. Therefore, we hypothesized that severe respiratory illness in the elderly is due to deficient CD8+ T cell responses. Results Here, we establish an aged mouse model of human metapneumovirus infection (HMPV) wherein aged C57BL/6 mice exhibit worsened weight loss, clinical disease, lung pathology and delayed viral clearance compared to young adult mice. Aged mice generate fewer lung-infiltrating HMPV epitope-specific CD8+ T cells. Those that do expand demonstrate higher expression of PD-1 and other inhibitory receptors and are functionally impaired. Transplant of aged T cells into young mice and vice versa, as well as adoptive transfer of young versus aged CD8+ T cells into Rag1 −/− recipients, recapitulates the HMPV aged phenotype, suggesting a cell-intrinsic age-associated defect. HMPV-specific aged CD8+ T cells exhibit a terminally exhausted TCF1/7− TOX+ EOMES+ phenotype. We confirmed similar terminal exhaustion of aged CD8+ T cells during influenza viral infection. Conclusions This study identifies terminal CD8+ T cell exhaustion as a mechanism of severe disease from respiratory viral infections in the elderly.

In this paper, we proposed an efficient and high-precision process for fabricating large-area microlens arrays using thermal reflow combined with ICP etching. When the temperature rises above the glass transition temperature, the polymer cylinder will reflow into a smooth hemisphere due to the surface tension effect. The dimensional differences generated after reflow can be corrected using etching selectivity in the following ICP etching process, which transfers the microstructure on the photoresist to the substrate. The volume variation before and after reflow, as well as the effect of etching selectivity using process parameters, such as RF power and gas flow, were explored. Due to the surface tension effect and the simultaneous molding of all microlens units, machining a 3.84 × 3.84 mm2 silicon microlens array required only 3 min of reflow and 15 min of ICP etching with an extremely low average surface roughness Sa of 1.2 nm.

Abstract X‐ray induced photodynamic therapy (X‐PDT) circumvents the poor penetration depth of conventional PDT with minimal radio‐resistance generation. However, conventional X‐PDT typically requires inorganic scintillators as energy transducers to excite neighboring photosensitizers (PSs) to generate reactive oxygen species (ROS). Herein, a pure organic aggregation‐induced emission (AIE) nanoscintillator (TBDCR NPs) that can massively generate both type I and type II ROS under direct X‐ray irradiation is reported for hypoxia‐tolerant X‐PDT. Heteroatoms are introduced to enhance X‐ray harvesting and ROS generation ability, and AIE‐active TBDCR exhibits aggregation‐enhanced ROS especially less oxygen‐dependent hydroxyl radical (HO•−, type I) generation ability. TBDCR NPs with a distinctive PEG crystalline shell to provide a rigid intraparticle microenvironment show further enhanced ROS generation. Intriguingly, TBDCR NPs show bright near‐infrared fluorescence and massive singlet oxygen and HO•− generation under direct X‐ray irradiation, which demonstrate excellent antitumor X‐PDT performance both in vitro and in vivo. To the best of knowledge, this is the first pure organic PS capable of generating both 1O2 and radicals (HO•−) in response to direct X‐ray irradiation, which shall provide new insights for designing organic scintillators with excellent X‐ray harvesting and predominant free radical generation for efficient X‐PDT.

BackgroundThe complex anatomical structure of the upper thoracic spine makes it challenging to achieve surgical exposure, resulting in significant surgical risks and difficulties. Posterior surgery alone fails to adequately address and reconstruct upper thoracic lesions due to limited exposure. While the anterior approach offers advantages in fully exposing the anterior thoracic lesions, the surgical procedure itself is highly intricate. Although there exist various anterior approaches for the upper thoracic spine, the incidence of upper thoracic spine lesions is relatively low. Consequently, there are limited reports on the treatment and reconstruction of upper thoracic spine lesions using the third rib small incision approach in the context of upper thoracic tuberculosis.MethodsWe collected data from four patients with upper thoracic tuberculosis who were admitted to our department between July 2017 and November 2022. The treatment for upper thoracic tuberculosis involved utilizing the third rib small incision approach, which included two cases of thoracic 3–4 vertebral tuberculosis, one case of thoracic 4 vertebral tuberculosis, and one case of thoracic 5 vertebral tuberculosis. Among the patients, three were positioned in the left lateral position, while one was positioned in the right lateral position. Prior to admission, all four patients received a two-week course of oral medication, consisting of isoniazid, rifampicin, pyrazinamide, and ethambutol. After the surgical procedure, they continued receiving anti-tuberculosis treatment for a duration of 12 months.ResultsThe average duration of the surgical procedure was 150 min, with an average blood loss of 500 ml. One patient exhibited symptoms of brachial plexus injury, which gradually improved after careful observation. All patients experienced primary wound healing, and no complications such as pulmonary infection, respiratory failure, or other adverse events were observed. Additionally, one patient showed elevated transaminase levels, leading to a modification in the anti-tuberculosis drug regimen from quadruple therapy to triple therapy.ConclusionThe treatment of upper thoracic tuberculosis through the third rib small incision technique is a very good surgical approach, which has the advantages of safety and effectiveness.

Here the authors investigated the direct collaboration between ubiquitinated histone H2B (ubH2B) with FACT at the nucleosome level. They found ubH2B enhances FACT’s chaperone property, recruits FACT to form a stable altered nucleosome state, and provides a key platform for transcription.

How the histone variant H2A.Z controls cell fate remains unclear. Here, the authors reveal that the H2A.Z interacting partner HMG20A plays a key role in regulating transcription during early head and heart development.

IntroductionThough the important effect of cultural identity on subjective well-being is widely acknowledged, the details of how different cultures’ unique features influence well-being remain to be revealed. To address this issue in the context of Chinese culture, the present study investigates whether and how the prominent features of Chinese culture—collectivism and red culture—shape Chinese people’s subjective well-being.MethodsThe Red Cultural Identity Scale, Subjective Well-Being Scale, Collectivism Scale, and Perspective-Taking Scale were used to assess 1,045 Chinese residents.ResultsThe results showed that red cultural identity positively predicted participants’ subjective well-being through the mediated role of collectivism. Furthermore, perspective-taking was found to moderate the mediating effect of collectivism.DiscussionThese results demonstrate that the way cultural identity predicts subjective well-being is highly correlated to specific cultural features, e.g., the opinion of values, which was significant in practice with a cross-cultural background.

Abstract Background Anterior cervical diskectomy and fusion (ACDF) has been widely accepted as a gold standard for patients with cervical spondylotic myelopathy (CSM). However, there was insufficient evidence to compare the changes in the cervical alignment with different fusion devices in a long follow-up period. This meta-analysis was performed to compare the radiologic outcomes and loss of correction (LOC) in cervical alignment of Zero-profile (ZP) device versus cage-plate (CP) construct for the treatment of CSM. Methods Retrospective and prospective studies directly comparing the outcomes between the ZP device and CP construct in ACDF were included. Data extraction was conducted and study quality was assessed independently. A meta-analysis was carried out by using fixed effects and random effects models to calculate the odds ratio and mean difference in the ZP group and the CP group. Results Fourteen trials with a total of 1067 participants were identified. ZP group had a lower rate of postoperative dysphagia at the 2- or 3-month and 6-month follow-up than CP group, and ZP group was associated with a decreased ASD rate at the last follow-up when compared with the CP group. The pooled data of radiologic outcomes revealed that there was no significant difference in postoperative and last follow-up IDH. However, postoperative and last follow-up cervical Cobb angle was significantly smaller in the ZP group when compared with the CP group. In subgroup analyses, when the length of the last follow-up was less than 3 years, there was no difference between two groups. However, as the last follow-up time increased, cervical Cobb angle was significantly lower in the ZP group when compared with the CP group. Conclusion Based on the results of our analysis, the application of ZP device in ACDF had a lower rate of postoperative dysphagia and ASD than CP construct. Both devices were safe in anterior cervical surgeries, and they had similar efficacy in correcting radiologic outcomes. However, as the last follow-up time increased, ZP group showed greater changes cervical alignment. In order to clarify the specific significance of LOC, additional large clinical studies with longer follow-up period are required.

Objective(s): Cisplatin (CDDP) is a highly effective chemotherapeutic agent, but its clinical application has been limited by nephrotoxicity. Tanshinone Ⅰ (T-I), a phenanthrenequinone compound extracted from the Chinese herb Danshen, has been used to improve circulation and treat cardiovascular diseases. The aim of this study was to investigate the protective effect of T-I on CDDP-induced nephrotoxicity in mice.Materials and Methods: The BALB/c mouse models of nephrotoxicity were established by a single intraperitoneal injection of 20 mg/kg CDDP on the first day of the experiment. Three hours prior to CDDP administration, the mice were dosed with 10 mg/kg and 30 mg/kg T-I for 3 consecutive days intraperitoneally to explore nephroprotection of T-I.Results: Treatment with T-I significantly reduced blood urea nitrogen and creatinine levels in serum observed in CDDP-administered mice, especially at a dose of 30 mg/kg. T-I at 30 mg/kg significantly decreased malondialdehyde levels and increased glutathione levels and the enzymatic activity of catalase in kidney tissue compared to CDDP. Additionally, T-I (30 mg/kg) significantly reversed the CDDP-decreased expression level of superoxide dismutase 2 protein in renal tissue. Histopathological evaluation of the kidneys further confirmed the protective effect of T-I. Conclusion: The findings of this study demonstrate that T-I can protect against CDDP-induced nephrotoxicity through suppression of oxidative stress.

Abstract Background Hepatocellular carcinoma (HCC) is among the most common forms of cancer and is associated with poor patient outcomes. The emergence of therapeutic resistance has hampered the efficacy of targeted treatments employed to treat HCC patients to date. In this study, we conducted a series of CRISPR/Cas9 screens to identify genes associated with synthetic lethality capable of improving HCC patient clinical responses. Methods CRISPR-based loss-of-function genetic screens were used to target 18,053 protein-coding genes in HCC cells to identify chemotherapy-related synthetic lethal genes in these cells. Synergistic effects were analyzed through in vitro and in vivo analyses, while related mechanisms were explored through RNA-seq and metabolomics analyses. Potential inhibitors of identified genetic targets were selected through high-throughput virtual screening. Results The inhibition of phosphoseryl-tRNA kinase (PSTK) was found to increase HCC cell sensitivity to chemotherapeutic treatment. PSTK was associated with the suppression of chemotherapy-induced ferroptosis in HCC cells, and the depletion of PSTK resulted in the inactivation of glutathione peroxidative 4 (GPX4) and the disruption of glutathione (GSH) metabolism owing to the inhibition of selenocysteine and cysteine synthesis, thus enhancing the induction of ferroptosis upon targeted chemotherapeutic treatment. Punicalin, an agent used to treat hepatitis B virus (HBV), was identified as a possible PSTK inhibitor that exhibited synergistic efficacy when applied together with Sorafenib to treat HCC in vitro and in vivo. Conclusions These results highlight a key role for PSTK as a mediator of resistance to targeted therapeutic treatment in HCC cells that functions by suppressing ferroptotic induction. PSTK inhibitors may thus represent ideal candidates for overcoming drug resistance in HCC.

Abstract The leader‐following consensus problem of a class of non‐strict feedback multi‐agent systems with unknown disturbances, this paper develops a novel adaptive event‐triggered control strategy ground on the consideration of the full state constraints. Combining the dynamic surface control and event triggering mechanism, the unknown external disturbances are estimated by designing a disturbance observer. In order to deal with unknown functions, this paper employs the neural networks. On purpose of keeping the output variable within a constraint boundary, the barrier Lyapunov function is chosen during the design course. Then, through the backstepping method and the Lyapunov stability theorem, it is proved that all signals in the closed‐loop systems are bounded, and the control performance of the closed‐loop system is ensured by selecting design parameters reasonably. Eventually, the availability of the control strategy is guaranteed through experimental example.

Abstract Human metapneumovirus (HMPV) is a leading cause of acute lower respiratory tract illness in children and adults. Repeated infections are common and can be severe in young, elderly, and immunocompromised persons due to short-lived protective humoral immunity. In turn, few protective T cell epitopes have been identified in humans. Thus, we infected transgenic mice expressing the common human HLA MHC-I allele B*07:02 (HLA-B7) with HMPV and screened a robust library of overlapping and computationally predicted HLA-B7 binding peptides. Six HLA-B7-restricted CD8+ T cell epitopes were identified using ELISPOT screening in the F, M, and N proteins, with M195–203 (M195) eliciting the strongest responses. MHC-tetramer flow cytometric staining confirmed HLA-B7 epitope-specific CD8+ T cells migrated to lungs and spleen of HMPV-immune mice. Immunization with pooled HLA-B7-restricted peptides reduced viral titer and protected mice from virulent infection. Finally, we confirmed that CD8+ T cells from HLA-B7 positive humans also recognize the identified epitopes. These results enable identification of HMPV-specific CD8+ T cells in humans and help to inform future HMPV vaccine design.

Abstract Epithelial cysts run a high risk of recurrence and conversion to sheet-like ingrowth after surgical intervention. In this retrospective study, we introduced a modified iridectomy for treatment of secondary epithelial iris cysts (EICs) in the anterior chamber. Twenty-nine patients (29 eyes) aged 2–61 years received “open iridectomy” for EICs between April 1995 and July 2019. After viscodissection, most of the cyst wall was cut using a 20-gauge aspiration cutter via a 2.5-mm clear corneal incision. The residue closely adhering to the iris stroma was remained to avoid photophobia and diplopia. At 3 months, best corrected visual acuity was ≥ 20/100 in 55.5% (15/27, except two pediatric patients with poor cooperation) of patients. Among the eight patients suffering partial corneal edema preoperatively, six patients received surgery treatment at 3–6.5 months, and the cornea in the other two patients became transparent after medication. In a mean follow-up of 47.4 months, recurrence occurred in 3 patients at 7, 37, and 118 months, respectively. The percentage of treatment success was 96%, 87%, and 65% at 1, 5, and 10 years, respectively. “Open iridectomy” was effective for EICs, with a minimal invasion, less damage to the corneal endothelium, and a low recurrence rate.

In the field of single-image super-resolution reconstruction, GAN can obtain the image texture more in line with the human eye. However, during the reconstruction process, it is easy to generate artifacts, false textures, and large deviations in details between the reconstructed image and the Ground Truth. In order to further improve the visual quality, we study the feature correlation between adjacent layers and propose a differential value dense residual network to solve this problem. We first use the deconvolution layer to enlarge the features, then extract the features through the convolution layer, and finally make a difference between the features before being magnified and the features after being extracted so that the difference can better reflect the areas that need attention. In the process of extracting the differential value, using the dense residual connection method for each layer can make the magnified features more complete, so the differential value obtained is more accurate. Next, the joint loss function is introduced to fuse high-frequency information and low-frequency information, which improves the visual effect of the reconstructed image to a certain extent. The experimental results on Set5, Set14, BSD100, and Urban datasets show that our proposed DVDR-SRGAN model is improved in terms of PSNR, SSIM, and LPIPS compared with the Bicubic, SRGAN, ESRGAN, Beby-GAN, and SPSR models.

Micro-optical gyroscopes (MOGs) place a range of components of the fiber-optic gyroscope (FOG) onto a silicon substrate, enabling miniaturization, low cost, and batch processing. MOGs require high-precision waveguide trenches fabricated on silicon instead of the ultra-long interference ring of conventional F OGs. In our study, the Bosch process, pseudo-Bosch process, and cryogenic etching process were investigated to fabricate silicon deep trenches with vertical and smooth sidewalls. Different process parameters and mask layer materials were explored for their effect on etching. The effect of charges in the Al mask layer was found to cause undercut below the mask, which can be suppressed by selecting proper mask materials such as SiO2. Finally, ultra-long spiral trenches with a depth of 18.1 μm, a verticality of 89.23°, and an average roughness of trench sidewalls less than 3 nm were obtained using a cryogenic process at −100 °C.

AIM: To investigate the association of axial length (AL), lens thickness (LT), and lens vault (LV) with postoperative anterior chamber angle metrics after laser peripheral iridotomy (LPI). METHODS: Prospective observational study of 69 patients (97 eyes) were diagnosed as primary angle-closure suspect (PACS), primary angle closure (PAC) or primary angle-closure glaucoma (PACG). AL, LT, anterior central chamber depth (ACD), angle opening distance (AOD), trabecular iris angle (TIA), and angle recess area (ARA) were measured before and 1wk after LPI. The association between AL, LT, LV with ACD, AOD, TIA, ARA were analyzed by comparing the differences between preoperative and postoperative measurements for anterior segment biometric parameters. RESULTS: ACD, AOD, TIA, and ARA were significantly increased after LPI (all P

Abstract Background Women who conceived with in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) are more likely to experience adverse pregnancy outcomes than women who conceived naturally. Cervical insufficiency (CI) is one of the important causes of miscarriage and premature birth, however there is no published data available focusing on the potential risk factors predicting CI occurrence in women who received IVF/ICSI treatment. This study aimed to identify the risk factors that could be integrated into a predictive model for CI, which could provide further personalized and clinically specific information related to the incidence of CI after IVF/ICSI treatment. Patients and methods This retrospective study included 4710 patients who conceived after IVF/ICSI treatment from Jan 2011 to Dec 2018 at a public university hospital. The patients were randomly divided into development (n = 3108) and validation (n = 1602) samples for the building and testing of the nomogram, respectively. Multivariate logistic regression was developed on the basis of pre-pregnancy clinical covariates assessed for their association with CI occurrence. Results A total of 109 patients (2.31%) experienced CI among all the enrolled patients. Body mass index (BMI), basal serum testosterone (T), gravidity and uterine length were associated with CI occurrence. The statistical nomogram was built based on BMI, serum T, gravidity and uterine length, with an area under the curve (AUC) of 0.84 (95% confidence interval: 0.76–0.90) for the developing cohort. The AUC for the validation cohort was 0.71 (95% confidence interval: 0.69–0.83), showing a satisfactory goodness-of-fit and discrimination ability in this nomogram. Conclusion The user-friendly nomogram which graphically represents the risk factors and a pre-pregnancy predicted tool for the incidence of CI in patients undergoing IVF/ICSI treatment, provides a useful guide for medical staff on individualized decisions making, where preventive measures could be carried out during the IVF/ICSI procedure and subsequent pregnancy.

This paper proposes an adaptive full state constrained consensus control strategy for a class of non-affine multi-agent systems with partially unknown control directions. Such non-affine systems commonly appear in practical applications and are difficult to control, especially with unknown control directions. Neural network is an excellent approximation tool to solve unknown parameters in the aforementioned consensus systems. The method of one-to-one mapping and mean value theorem can eliminate coupling terms and guarantee that the states of each agent are not violated the predetermined time-varying dynamic constraint boundary. In this way, the original systems can be transformed into an equivalent unconstrained systems, and the transformed systems obtained has the same consensus with the original systems. Considering that directions of control are partially unknown, the Nussbaum function can solve this problem in a novel way. Then the stability of the systems can be proved by Lyapunov function and all signals in the closed-loop systems are bounded. In the end, the simulation demonstrates the effectiveness of the proposed method.

Toosendanin (TSN) is a triterpenoid from the fruit or bark of Melia toosendan Sieb et Zucc, which has clear antitumor and insecticidal activities, but it possesses limiting hepatotoxicity in clinical application. Autophagy is a degradation and recycling mechanism to maintain cellular homeostasis, and it also plays an essential role in TSN-induced hepatotoxicity. Nevertheless, the specific mechanism of TSN on autophagy-related hepatotoxicity is still unknown. The hepatotoxicity of TSN in vivo and in vitro was explored in this study. It was found that TSN induced the upregulation of the autophagy-marker microtubule-associated proteins 1A/1B light chain 3B (LC3B) and P62, the accumulation of autolysosomes, and the inhibition of autophagic flux. The middle and late stages of autophagy were mainly studied. The data showed that TSN did not affect the fusion of autophagosomes and lysosomes but significantly inhibited the acidity, the degradation capacity of lysosomes, and the expression of hydrolase cathepsin B (CTSB). The activation of autophagy could alleviate TSN-induced hepatocyte damage. TSN inhibited the expression of transcription factor EB (TFEB), which is a key transcription factor for many genes of autophagy and lysosomes, such as CTSB, and overexpression of TFEB alleviated the autophagic flux blockade caused by TSN. In summary, TSN caused hepatotoxicity by inhibiting TFEB-lysosome-mediated autophagic flux and activating autophagy by rapamycin (Rapa), which could effectively alleviate TSN-induced hepatotoxicity, indicating that targeting autophagy is a new strategy to intervene in the hepatotoxicity of TSN.

TET mediated RNA-hydroxymethylation (5hmC) has been detected in mammals, but its physiological role remains unclear. Here the authors map 5hmC during embryonic stem cell (ESC) differentiation and find that Tet-mediated RNA hydroxymethylation reduces the stability of crucial pluripotency related transcripts.

Interval type-2 fuzzy logic systems (IT2 FLSs) have been widely used in many areas. Among which, type-reduction (TR) is an important block for theoretical study. Noniterative algorithms do not involve the complicated iteration process and obtain the system output directly. By discovering the inner relations between discrete and continuous noniterative algorithms, this paper proposes three types of weighted-based noniterative according to the Newton-Cotes quadrature formulas in numerical integration techniques. Moreover, the continuous noniterative algorithms are considered as the benchmarks for computing. Four simulation experiments are provided to illustrate the performances of weighted-based noniterative algorithms for computing the defuzzified values of IT2 FLSs. Compared with the original noniterative algorithms, the proposed weighted-based algorithms can obtain smaller absolute errors and faster convergence speeds under the same sampling rate, which afford the potential values for designing T2 FLSs.

Type-reduction (TR) is a key block for interval type-2 fuzzy logic systems (IT2 FLSs). In general, Karnik-Mendel (KM) (or enhanced Karnik-Mendel (EKM)) algorithms are used to perform the TR. These two types of algorithms have the advantage of preserving the uncertainties of membership functions (MFs) flow in IT2 FLSs. This paper gives the initialization explanations of KM and EKM algorithms, and proposes reasonable initialization enhanced Karnik-Mendel (RIEKM) algorithms for centroid TR of IT2 FLSs. By considering the accurate continuous Nie-Tan (CNT) algorithms as the benchmark, four computer simulation examples are adopted to illustrate and analyze the performances of RIEKM algorithms for solving the centroid TR and defuzzification of IT2 FLSs. Compared with the EKM algorithms, the proposed RIEKM algorithms have smaller absolute errors and faster convergence speeds, which afford the potential value for designing and applying IT2 FLSs.

Abstract Background The plant chloroplast is essential for photosynthesis and other cellular processes, but an understanding of the biological mechanisms of plant chloroplast development are incomplete. Results A new temperature-sensitive white stripe leaf 9 ( wsl9 ) rice mutant is described. The mutant develops white stripes during early leaf development, but becomes green after the three-leaf stage under field conditions. The wsl9 mutant was albinic when grown at low temperature. Gene mapping of the WSL9 locus, together with complementation tests indicated that WSL9 encodes a novel protein with an HNH domain. WSL9 was expressed in various tissues. Under low temperature, the wsl9 mutation caused defects in splicing of rpl2, but increased the editing efficiency of rpoB . Expression levels of plastid genome-encoded genes, which are transcribed by plastid-coded RNA polymerase (PEP), chloroplast development genes and photosynthesis-related genes were altered in the wsl9 mutant. Conclusion WSL9 encodes an HNH endonuclease domain-containing protein that is essential for early chloroplast development. Our study provides opportunities for further research on regulatory mechanisms of chloroplast development in rice.

PurposeTo determine the impact of ovarian endometrioma per se on in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes.MethodsThis retrospective study was conducted using two groups. The endometrioma group consisted of 862 women with infertility who had ovarian endometriomas and underwent their first ovarian stimulation for IVF/ICSI treatment between January 2011 to December 2019 at a public university hospital. A non-endometrioma comparison group, comprising 862 women with other infertility factors, was matched according to maternal age, body mass index (BMI), and infertility duration. Ovarian reserve and response and IVF/ICSI and pregnancy outcomes between the two groups were analyzed. Multivariate logistic regression (MLR) analysis was conducted on the basis of clinical covariates assessed for their association with live birth.ResultsThe results showed that significantly lower antral follicle count (AFC), anti-Müllerian hormone (AMH), ovarian sensitivity index (OSI), oocyte maturation and fertilization rates, blastocyst rate, number of oocytes retrieved, and available embryos were found in women with endometrioma compared with the control, respectively (P < 0.05). The cumulative live birth rate per patient in women with endometrioma was lower than that of women without endometrioma (39.32% vs. 46.87%, P = 0.002). In women with endometrioma, those who underwent surgical intervention prior to IVF/ICSI treatment had higher maturation (86.03% vs. 83.42%, P = 0.003), fertilization (78.16% vs. 74.93%, P = 0.004), and top-quality embryo rates (42.94% vs. 39.93%, P = 0.097) but had fewer oocytes retrieved (8.01 ± 5.70 vs. 9.12 ± 6.69, P = 0.013) than women without surgery. However, live birth rates were comparable between women with endometrioma and women in the control group, regardless of whether they had a prior history of ovarian surgery. MLR analysis showed no correlation between endometrioma per se and live birth after being adjusted for number of top-quality embryos transferred and stage of embryo transfer.ConclusionsThe data from this study supported the conclusion that ovarian endometrioma negatively impacts oocyte quality and quantity, but not overall pregnancy outcomes, in women undergoing IVF/ICSI treatment. Endometrioma lowers the cumulative live birth rate by decreasing the number of embryos. Surgical excision of endometrioma prior to IVF/ICSI can partly improve oocyte maturation and fertilization rates but not pregnancy outcomes.

Female breast cancer has become the most commonly occurring cancer worldwide. Although it has a good prognosis under early diagnosis and appropriate treatment, breast cancer metastasis drastically causes mortality. The process of metastasis, which includes cell epithelial–mesenchymal transition, invasion, migration, and colonization, is a multistep cascade of molecular events directed by gene mutations and altered protein expressions. Ubiquitin modification of proteins plays a common role in most of the biological processes. E3 ubiquitin ligase, the key regulator of protein ubiquitination, determines the fate of ubiquitinated proteins. E3 ubiquitin ligases target a broad spectrum of substrates. The aberrant functions of many E3 ubiquitin ligases can affect the biological behavior of cancer cells, including breast cancer metastasis. In this review, we provide an overview of these ligases, summarize the metastatic processes in which E3s are involved, and comprehensively describe the roles of E3 ubiquitin ligases. Furthermore, we classified E3 ubiquitin ligases based on their structure and analyzed them with the survival of breast cancer patients. Finally, we consider how our knowledge can be used for E3s’ potency in the therapeutic intervention or prognostic assessment of metastatic breast cancer.

Summary: Breast cancer stem cells (BCSCs) play essential roles in tumor formation, drug resistance, relapse, and metastasis. NANOG is a protein required for stem cell self-renewal, but the mechanisms by which it performs this function are poorly understood. Here, we show that hypoxia-inducible factor 1α (HIF-1α) is required for NANOG-mediated BCSC enrichment. Mechanistically, NANOG is recruited by HIF-1 to cooperatively activate transcription of the TERT gene encoding the telomerase reverse transcriptase that maintains telomere length, which is required for stem cell self-renewal. NANOG stimulates HIF-1 transcriptional activity by recruitment of the deubiquitinase USP9X, which inhibits HIF-1α protein degradation, and by stabilizing HIF-1α interaction with the coactivator p300, which mediates histone acetylation. Our results delineate a cooperative transcriptional mechanism by which HIF-1 and NANOG mediate BCSC self-renewal.

Based on environmental monitoring data and meteorological observation data of the Chinese major energy province, Shanxi, from 2015 to 2020, using the satellite remote sensing data of Atmospheric Infrared Sounder Instrument (AIRS) and Ozone Monitoring Instrument (OMI) in 2017, we analyzed the characteristics of surface ozone (O3) pollution and its correlation with meteorological factors, as well as the vertical distribution of O3 in typical pollution cities in Shanxi Province. The results showed that surface O3 became the primary pollutant in Shanxi. Surface O3 has shown a zonal distribution with a high level in the south and a low level in the north region since 2017. Surface O3 pollution was severe in 2019, and the maximum daily 8 h running average of O3 (MDA8 O3) decreased, but annual mean O3 in northern and central regions showed a slow rising trend in 2020. Comprehensive analyses of the influence of meteorological factors on surface O3 indicated that O3 pollution in Linfen, Yuncheng and Taiyuan was mainly caused by local photochemical reactions, while that in Jincheng, Xinzhou, Lvliang and Yangquan resulted from regional transports. O3 volume mixing ratios (VMR) in the middle and lower troposphere generally increased with altitude, peaking at 120 ppbv at approximately 400 hPa. The positive vertical gradient of O3 in the boundary layer was obvious in Taiyuan in summer and significant in the surface layer in Taiyuan and Linfen during winter and spring, which was associated with greater atmospheric dynamic stability and suppressed vertical mixing. Due to the lack of direct detection of O3 in the lower troposphere in this region, O3 vertical distribution retrieved by satellite observation is critical for the study of vertical mixing and transport of local O3, as well as its regional transport characteristics.

In this paper, a high-precision, low-cost, batch processing nanoimprint method is proposed to process a spherical microlens array (MLA). The nanoimprint mold with high surface precision and low surface roughness was fabricated by single-point diamond turning. The anti-sticking treatment of the mold was carried out by perfluorooctyl phosphoric acid (PFOPA) liquid deposition. Through the orthogonal experiment of hot embossing with the treated mold and subsequent inductively coupled plasma (ICP) etching, the microstructure of MLA was transferred to the silicon substrate, with a root mean square error of 17.7 nm and a roughness of 12.1 nm Sa. The average fitted radius of the microlens array units is 406.145 µm, which is 1.54% different from the design radius.

ObjectiveThis study aimed to compare the ultra-long gonadotropin-releasing hormone agonist (GnRH-a) protocol and the long GnRH-a protocol during in vitro fertilization (IVF) or intracytoplasmic sperm (ICSI) treatment on fertility outcomes in women with adenomyosis.Materials and MethodsThis study was a retrospective cohort study. From January 2011 to May 2018, a total of 371 fresh IVF/ICSI cycles were included. Among the cycles included, 237 cycles of 212 women underwent the ultra-long GnRH-a protocol, while 134 cycles of 116 women underwent the long GnRH-a protocol. The rates of implantation, clinical pregnancy per embryo transfer, live birth, and early miscarriage were estimated between the compared protocols.ResultsIn the study, the early miscarriage rate in women undergoing the ultra-long GnRH-a protocol was significantly lower than those undergoing the long GnRH-a protocol (12.0% versus 26.5%, p = 0.045), whereas the differences in the rates of biochemical pregnancy, implantation, clinical pregnancy, and live birth in women between the two groups showed no statistical significance. The pregnancy outcomes were also sub-analyzed according to the adenomyotic region (diffuse and focal). As for diffuse adenomyosis, the rates of clinical pregnancy and live birth in women undergoing the ultra-long GnRH-a protocol were significantly higher than those undergoing the long GnRH-a protocol (55.3% versus 37.9%, p = 0.025; 43.4% versus 25.9%, p = 0.019, respectively). However, pregnancy outcomes showed no difference between the two protocols in women with focal adenomyosis.ConclusionsThe ultra-long GnRH-a protocol during IVF/ICSI improves pregnancy outcomes in women with adenomyosis, especially in women with diffuse adenomyosis when compared with the long GnRH-a protocol.

The aim was to develop a nanocarrier based on polyoxyl 15 hydroxystearate (Kolliphor® HS15, HS15) micelles for the solubility, stability, and ocular delivery of myricetin (Myr). An optimized ratio of HS15 and Myr was prepared to fabricate HS15-Myr micelle ophthalmic solution. Myr-encapsulating HS15 micelles (HS15-Myr micelles) were subjected to physicochemical characterizations. The chemical stability of Myr in HS15 micelles and storage stability of HS15-Myr micelle ophthalmic solutions were evaluated. In vitro parallel artificial membrane permeability assay and antioxidant activity of Myr in HS15 micelles were also measured. In vivo ocular tolerance, corneal permeation, and anti-inflammatory efficacy studies were conducted following ocular topical administration. HS15-Myr micelles were successfully prepared and presented transparent appearance with high encapsulation (96.12 ± 0.31%), ultra-small micelle size (a mean diameter of 12.17 ± 0.73 nm), uniform size distribution (polydispersity index [PDI] = 0.137 ± 0.013), and negative surface charge (− [4.28 ± 0.42] mV). Myr in HS15 micelle solution demonstrated higher aqueous stability than the free Myr solution among the accepted pH range for eyedrops. HS15-Myr micelle ophthalmic solution demonstrated high storage stability at 4 °C and 25 °C. HS15 micelles could significantly improve in vitro antioxidant activity and faster membrane permeation of Myr. No irritations or corneal damage were revealed in rabbit eyes after ocular administration of HS15-Myr micelle solution. In vivo corneal permeation study demonstrated that HS15-Myr micelles could penetrate the cornea efficiently in mouse eyes. Further, HS15-Myr micelles also demonstrated significant in vivo anti-inflammatory activity. It can be concluded that HS15 micelles are a potential ophthalmic delivery nanocarrier for poorly soluble drugs such as Myr.

Myricetin (Myr) is a naturally occurring flavonoid exhibiting diverse biological and pharmacological properties, but its characteristics such as water insolubility, poor aqueous stability, and poor bioavailability limit its clinical application, including in ophthalmology. To increase its clinical application in ophthalmology, Myr was designed to be encapsulated in a polyvinyl caprolactam–polyvinyl acetate–polyethylene glycol graft copolymer (PVCL-PVA-PEG) polymeric micelles to increases its aqueous solubility, stability, and corneal permeability to promote its efficacy in eye disease treatments. Thus, the Myr micelle ophthalmic solution was prepared and characterized encapsulation efficiency (EE), micelle size, and zeta potential. The chemical stability of Myr and the short-term storage stability of the Myr micelle ophthalmic solution were evaluated, followed by in vitro cytotoxicity and in vivo ocular irritation; in vitro cellular uptake and in vivo corneal permeation; and in vitro antioxidant activity and in vivo anti-inflammatory efficacy were also further evaluated. Myr could be incorporated into micelles with high EE. PVCL-PVA-PEG micelles significantly enhanced Myr’s aqueous solubility and chemical stability. The Myr micelle ophthalmic solution also showed high storage stability. In rabbits, the Myr micelle ophthalmic solution displayed good in vitro cellular tolerance. Remarkable improvements in in vitro cellular uptake and in vivo corneal permeation were also observed in the Myr micelle ophthalmic solution, and significant improvements in the in vitro antioxidant activity and in vivo anti-inflammatory efficacy were also obtained. Overall, these results supported that the Myr micelle ophthalmic solution could be a promising nanomedicine for ocular tissues.

Objectives: Ginsenosides Rb1 (Rb1) could form micelles in aqueous solutions. Self-assembled Rb1 micelles could potentially be utilized as ocular drug delivery system, and it was postulated that the encapsulation of a medicine within Rb1 micelles might strengthen the drug’s therapeutic action and reduce side effects. Methods: Diclofenac-loaded Rb1 micelles (Rb1-Dic micelles) were formulated, optimized, and then further evaluated for in vitro cytotoxicity/in vivo ocular irritation, in vivo corneal permeation, and in vivo anti-inflammatory efficacy. Results: Rb1 self-assembled into micelles with ultra-small particle size (

The problem of adaptive finite-time fault-tolerant control (FTC) and output constraints for a class of uncertain nonlinear half-vehicle active suspension systems (ASSs) are investigated in this work. Markovian variables are used to denote in terms of different random actuators failures. In adaptive backstepping design procedure, barrier Lyapunov functions (BLFs) are adopted to constrain vertical motion and pitch motion to suppress the vibrations. Unknown functions and coefficients are approximated by the neural network (NN). Assisted by the stochastic practical finite-time theory and FTC theory, the proposed controller can ensure systems achieve stability in a finite time. Meanwhile, displacement and pitch angle in systems would not violate their maximum values, which imply both ride comfort and safety have been enhanced. In addition, all the signals in the closed-loop systems can be guaranteed to be semiglobal finite-time stable in probability (SGFSP). The simulation results illustrate the validity of the established scheme.

This paper proposes an adaptive fuzzy distributed consensus tracking control scheme for a class of uncertain nonlinear dynamic multiagent systems (MASs) with state time-varying delays and state time-varying constraints. The existing controllers with Lyapunov–Krasovskii functions (LKFs) were not suitable to address time-varying delays and time-varying constraints in nonlinear MASs simultaneously. State constraints further increase the difficulty of controller design and stability analysis, especially for nonstrict feedback systems. Fuzzy logic systems (FLSs) tackle the approximation of unknown dynamics functions and parameters. Especially when the distributed consensus tracking error is infinitely close to the origin, although there is no singular value, it would lead to the rapid growth of control rate or uncontrollability. Constructing appropriate piecewise functions can effectively avoid the above occurrence and accelerate convergence. Based on Lyapunov stability theory and algebraic graph theory, the constructed tracking control can ensure states within defined time-varying constraint bounds and eliminate the influence of time delays. All signals in closed-loop systems can be guaranteed semiglobally uniformly ultimately bounded (SUUB). Finally, the validity of the theoretical method is verified by the simulation.

For efficient plant reproduction, seed dormancy delays seed germination until the environment is suitable for the next generation growth and development. The phytohormone abscisic acid (ABA) plays important role in the induction and maintenance of seed dormancy. Previous studies have identified that WRKY transcription factors can regulate ABA signaling pathway. Here, we identified an Oswrky29 mutant with enhanced dormancy in a screen of T-DNA insertion population. OsWRKY29 is a member of WRKY transcription factor family which located in the nuclear. The genetic analyses showed that both knockout and RNAi lines of OsWRKY29 had enhanced seed dormancy whereas its overexpression lines displayed reduced seed dormancy. When treated with ABA, OsWRKY29 knockout and RNAi lines showed greater sensitivity than its overexpression lines. In addition, the expression levels of ABA positive response factors OsVP1 and OsABF1 were higher in the OsWRKY29 mutants but were lower in its overexpression lines. Further assays showed that OsWRKY29 could bind to the promoters of OsABF1 and OsVP1 to inhibit their expression. In summary, we identified a new ABA signaling repressor OsWRKY29 that represses seed dormancy by directly downregulating the expression of OsABF1 and OsVP1.

The purpose of this article is to introduce and analyze the feasibility of simultaneously combined anterior‐posterior approaches for subaxial cervical circumferential reconstruction in sitting position. A retrospective case review was performed for above surgery procedure. A 79‐year‐old man was confirmed subaxial cervical fracture and dislocation with facet locked by radiological examination, and the involved levels were C5‐6. According to American Spinal Injury Association (ASIA) classification, the impairment scale was grade B. And the Subaxial Cervical Spine Injury and Severity Score (SLIC) were 9. The patient was restricted in sitting position with traction on a halo in extension to immobilize the head during the operation. A posterior laminectomy and pedicle screws insertion to the involved cervical spine was performed firstly. And then the anterior discectomy and strut graft were accomplished through an anterior cervical approach. The final fixation was finished by clamping the strut graft with pedicle screw system. Total blood loss was 600 ml and the total operating time was 150 min. The patient was followed up for 6 months. The symptom of neck pain improved distinctly and no evidence about implant failure was noted. Neurological status improvement was confirmed and the ASIA scale was improved to grade C. We believed that the simultaneously combined anterior‐posterior approach in sitting position was safe and more advantageous for appropriate cases.

D-Lactate is oxidized by two classes of D-lactate dehydrogenase (D-LDH), namely, NAD-dependent and NAD-independent D-LDHs. Little is known about the characteristics and biological functions of D-LDHs in rice. In this study, a functional NAD-independent D-LDH (LOC_Os07g06890) was identified in rice, as a result of alternative splicing events. Characterization of the expression profile, subcellular localization, and enzymatic properties of the functional OsD-LDH revealed that it is a mitochondrial cytochrome-c-dependent D-LDH with high affinity and catalytic efficiency. Functional analysis of OsD-LDH RNAi transgenic rice demonstrated that OsD-LDH participates in methylglyoxal metabolism by affecting the activity of the glyoxalase system and aldo-keto reductases. Under methylglyoxal treatment, silencing of OsD-LDH in rice resulted in the accumulation of methylglyoxal and D-lactate, the decrease of reduced glutathione in leaves, and ultimately severe growth inhibition. Moreover, the detached leaves of OsD-LDH RNAi plants were more sensitive to salt stress. However, the silencing of OsD-LDH did not affect the growth under photorespiration conditions. Our results provide new insights into the role of NAD-independent D-LDHs in rice.

To compare the efficacy and safety of current treatments in diabetic macular edema (DME).PubMed, Embase and CENTRAL were systematically reviewed for randomized controlled trials of current treatments in DME through August 2015. Data on the mean change of best-corrected visual acuity (BCVA) and central macular thickness (CMT) were extracted, and adverse events (AEs) were collected.A total of 21 trials were included in our network meta-analysis. Intravitreal ranibizumab improved BCVA most significantly (OR: +7.01 95%CI (2.56 to 11.39)) in 6 months and intravitreal aflibercept (+8.19 (5.07 to 11.96)) in 12 months. Intravitreal triamcinolone combined with LASER decreased CMT most significantly (-111.34 (-254.61 to 37.93)) in 6 months and intravitreal aflibercept (-110.83 (-190.25 to -35.27)) in 12 months. Compared with the relatively high rate of ocular AEs in the groups with administration of steroids, systematic AEs occurred more frequently in the groups with vascular endothelial growth factor inhibitors involved.Our analysis confirms that intravitreal aflibercept is most favorable with both BCVA improvement and CMT decrease than other current therapies in the management of DME within 12 months. Vascular endothelial growth factor inhibitors for DME should be used with caution due to systematic AEs. Combined intravitreal triamcinolone with LASER has a stronger efficacy in decreasing CMT than the other interventions in the early stage after injection. More high-quality randomized controlled trials will be necessary.

We prove the local existence, blow-up, global existence, and stability of solutions to the initial boundary value problem for Euler-Bernoulli plate equation with variable coefficients.

The pathogenesis of accelerated liver damage in subjects coinfected with hepatitis C virus (HCV) and human immunodeficiency virus type 1 (HIV-1) remains largely unknown. Recent studies suggest that ongoing chronic liver inflammation is responsible for the liver injury in HCV-infected patients. We aimed to determine whether HIV-1 coinfection altered intrahepatic inflammatory profiles in HCV infection, thereby hastening liver damage. We used a real-time RT-PCR-based array to comparatively analyze intrahepatic inflammation gene profiles in liver biopsy specimens from HCV-infected (n = 16), HCV/HIV-1-coinfected (n = 8) and uninfected (n = 8) individuals. We then used human hepatocytes to study the molecular mechanisms underlying alternations of the inflammatory profiles. Compared with uninfected individuals, HCV infection and HCV/HIV-1 coinfection markedly altered expression of 59.5% and 50.0% of 84 inflammation-related genes tested, respectively. Among these genes affected, HCV infection up-regulated the expression of 24 genes and down-regulated the expression of 26 genes, whereas HCV/HIV-1 coinfection up-regulated the expression of 21 genes and down-regulated the expression of 21 genes. Compared with HCV infection, HCV/HIV-1 coinfection did not dramatically affect intrahepatic gene expression profiles of cytokines and their receptors, but profoundly altered expression of several chemokine genes including up-regulation of the CXCR3-associated chemokines. Human hepatocytes produced these chemokines in response to virus-related microbial translocation, viral protein stimulation, and antiviral immune responses.HIV-1 coinfection profoundly alters intrahepatic chemokine but not cytokine profiles in HCV-infected subjects. The altered chemokines may orchestrate the tissue-specific and cell-selective trafficking of immune cells and autoimmunity to accelerate liver disease in HCV/HIV-1 coinfection.