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Ketogluconic acid is widely applied in several industries as the bio-precursor of vitamin C and tartaric acid, while the selective production of 2-kGA or 5-kGA from glucose is so far still a challenge for chemical and biotechnical processes.

Quantifying vehicle-bridge interaction mechanism is critical for bridge safety design, transportation weight control, condition assessments in maintenance, and structural health monitoring. In this paper, the stochastic non-stationary characteristics of a bridge under vehicle-bridge interaction are investigated. The response of the bridge under the loading of vehicles is, respectively, depicted in Fourier spectrum, spectrogram, and Hilbert spectrum. Both Fourier spectrum and spectrogram exhibit some cluster bands. The Hilbert spectrum exhibits time-varying frequencies in the proximity of low bridge natural modes, which suggests possible non-linear and non-stationary characteristics. The stochastic and non-stationary properties are further characterized by using bispectrum and recurrence analysis, and the weak nonlinear properties are characterized by using nonlinear invariants. The free-decay response of bridge (vehicle left the bridge) exhibits linear properties, which is correlated with the natural modes of bridge, whereas the bridge vibrations under moving vehicle exhibit complicated stochastic non-stationary and non-linear properties. These provide the insights into the conventional modal analysis-based approaches for heavy vehicle-loaded bridge condition assessments and structural health monitoring.

Although public transport development has been widely addressed in extant urban research, everyday practices in transport spaces and their broader implications for urbanizing China are relatively less studied. Building on de Certeau’s concept of “tactics” and the literature on urban mobility, this study employs spatial analysis and ethnography to investigate the case of the Shanghainan Railway Station (SHNS) in China that had become underused after its traffic was directed away to new stations in the same network. By 2017, this decline had turned an architectural icon designed for efficiency and speed into a place where many unlikely social groups gathered daily. We followed a charity team serving the homeless seeking shelter there to understand how this modern structure was appropriated to cater to those who survived in the trails of development. The case of the SHNS reveals the uneven consequences of urbanization brought about by increasing connectivity in Chinese society and highlights how tactics can be a form of social infrastructure exhibiting degrees of institutional stability and translocal solidarities. It also points to the theoretical significance of turning our attention from the frontier to the trail of development as a productive space where the state, civil society and marginalized emerge temporarily in pastoral forms.

The rapid development of Internet technology in today's era has provided more possibilities for the transformation, upgrading and in-depth development of all walks of life. In the face of the large-scale spread of new domestic and international epidemics, most traditional industries have encountered difficulties in their development. This paper focuses on the development of China's tourism industry, taking Yunnan Province of China as the exploration direction, starting from the analysis of the integration of tourism and Internet technology in Yunnan, and the possibility of promoting its online tourism development, points out its current shortcomings, and puts forward the development countermeasures of its online tourism, so as to boost the development of new forms of tourism in Yunnan and the deep transformation and integration of Internet technology.

Controlling temperature and pressure during the supercritical carbon dioxide (scCO2) process can change the mount of CO2 entered in polypropylene (PP) phase, thereby changing the mechanical properties of materials. The effect of scCO2 treatment on the crystallization behavior is different in the semi-molten and molten states. This study investigates the PP treated with scCO2 near the melting point and at various pressures, and explores the effects of temperature and pressure on the crystal structure, lamellar structure, and thermodynamic properties of PP. The results show that at a melting temperature of 165 °C, scCO2 can enhances the ability of PP molecules to makes the PP crystal region more regular, and forms larger microcrystals and lamellae. Additionally, increasing the pressure can make more CO2 enter the PP crystal region and further improve the regularity of the crystal. At a semi-melting temperature of 155 °C, scCO2 is primarily in the amorphous region because it is difficult to enter the PP crystal region. Even if increasing the pressure, it has little effect on the crystal size and lamellar thickness of PP. The research has significant implications for developing and utilizing scCO2 to remove ash from materials.

Background Fungal keratitis is a severe sight-threatening ocular infection, without effective treatment strategies available now. Calprotectin S100A8/A9 has recently attracted great attention as a critical alarmin modulating the innate immune response against microbial challenges. However, the unique role of S100A8/A9 in fungal keratitis is poorly understood.Methods Experimental fungal keratitis was established in wild-type and gene knockout mice by infecting mouse corneas with Candida albicans. The degree of mouse cornea injuries was evaluated by clinical scoring. To interrogate the molecular mechanism in vitro, macrophage RAW264.7 cell line was challenged with Candida albicans or recombinant S100A8/A9 protein. Label-free quantitative proteomics, quantitative real-time PCR, western blotting and immunohistochemistry were conducted in this research.Results Herein, we characterized the proteome of mouse corneas infected with Candida albicans and found that S100A8/A9 was robustly expressed at the early stage of the disease. S100A8/A9 significantly enhanced disease progression by promoting NLRP3 inflammasome activation and Caspase-1 maturation, accompanied by increased accumulation of macrophages in infected corneas. In response to Candida albicans infection, toll-like receptor 4 (TLR4) sensed extracellular S100A8/A9 and acted as a bridge between S100A8/A9 and NLRP3 inflammasome activation in mouse corneas. Furthermore, the deletion of TLR4 resulted in noticeable improvement in fungal keratitis. Remarkably, NLRP3/GSDMD-mediated macrophage pyroptosis in turn facilitates S100A8/A9 secretion during Candida albicans keratitis, thus forming a positive feedback cycle that amplifies the proinflammatory response in corneas.Conclusions The present study is the first to reveal the critical roles of the alarmin S100A8/A9 in the immunopathology of Candida albicans keratitis, highlighting a promising approach for therapeutic intervention in the future.

Understanding the factors that drive diversification of taxa across the tree of life is a key focus of macroevolutionary research. While the effects of life history, ecology, climate and geography on diversity have been studied for many taxa, the relationship between molecular evolution and diversification has received less attention. However, correlations between rates of molecular evolution and diversification rate have been detected in a range of taxa, including reptiles, plants and birds. A correlation between rates of molecular evolution and diversification rate is a prediction of several evolutionary theories, including the evolutionary speed hypothesis which links variation in mutation rates to differences in speciation rates. If it is widespread, such correlations could also have significant practical impacts, if they are not adequately accounted for in phylogenetic inference of evolutionary rates and timescales. Ray-finned fish (Actinopterygii) offer a prime target to test for this relationship due to their extreme variation in clade size suggesting a wide range of diversification rates. We employ both a sister-pairs approach and a whole-tree approach to test for correlations between substitution rate and net diversification. We also collect life history and ecological trait data and account for potential confounding factors including body size, latitude, max depth and reef association. We find evidence to support a relationship between diversification and synonymous rates of nuclear evolution across two published backbone phylogenies, as well as weak evidence for a relationship between mitochondrial nonsynonymous rates and diversification at the genus level.

Exchange in ideas between language evolution and biological evolution has a long history, due to a shared theoretical foundation between language and biology as two evolving systems. Both systems evolve in terms of the frequency of a variant in a population for each of a large number of variables, that is how often a particular variant of a language variable is used in a speaker community and how many individuals in a biological population carry a particular variant of a gene. The way these frequencies change has been modelled under a similar mathematical framework. Here, I show how we can use concepts from genome wide association studies that identify the source of natural selection and the genes under selection in a biological population to study how social factors affect the usage of language variables in a speaker community or how some social groups use some language variables differently from other groups. Using the Gurindji Kriol language as a case study, I show how this approach unifies existing mathematical and statistical tools in studying language evolution over a large number of speakers and a large number of language variables, which provides a promising link between micro- and macro-evolution in language. The approach is named BayesVarbrul and is ready to apply to datasets other than the Gurindji Kriol dataset, including existing corpus data. The code and the instructions are available at https://github.com/huaxia1985/BayesVarbrul.

Fe2(MoO4)3 assembled by cross-stacking of porous nanosheets is well designed with impressive Al-storage performance and its Al3+ intercalation/extraction mechanism is also clarified.

Existing video captioning methods usually ignore the important fine-grained semantic attributes, the video diversity, as well as the association and motion state between objects within and between frames. Thus, they cannot adapt to small sample data sets. To solve the above problems, this paper proposes a novel video captioning model and an adversarial reinforcement learning strategy. Firstly, an object-scene relational graph model is designed based on the object detector and scene segmenter to express the association features. The graph is encoded by the graph neural network to enrich the expression of visual features. Meanwhile, a trajectory-based feature representation model is designed to replace the previous data-driven method to extract motion and attribute information, so as to analyze the object motion in the time domain and establish the connection between the visual content and language under small data sets. Finally, an adversarial reinforcement learning strategy and a multi- branch discriminator are designed to learn the relationship between the visual content and corresponding words so that rich language knowledge is integrated into the model. Experimental results on three standard datasets and one small sample dataset indicate that our proposed method achieves state-of-the-art performance. Also, the ablation experiments and visualization results verify the effectiveness of proposed each strategy.

An eco-friendly wholly biological method for galactaric acid preparation from pectin with three steps including enzymolysis, purification and catalysis.

High-purity glycolic acid (GA) is a necessary building block unit of medical materials which provides a promising value-added utilization of ethylene glycol (EG).

Objective: To investigate whether genomic instability (GI)-derived long non-coding RNAs (lncRNAs) have a prognostic impact on the patients with endometrial cancer. Material and methods: Patients with Uterine Corpus Endometrial Carcinoma (UCEC) were selected from The Cancer Genome Atlas (TCGA) database. Systematic bioinformatics analyses were performed, including Pearson correlations, GO and KEGG enrichment analysis, bivariate and multiple logistic regression analysis, and Kaplan–Meier (KM) method. Results: A total of 552 UCEC samples were included in the study. The differentially expressed lncRNAs (DELs) were identified, including 79 down-regulated lncRNAs and 31 up-regulated lncRNAs. Bivariate logistic regression analysis showed that 19 GI-derived lncRNAs were prognostic factors. By further multivariate logistic regression analysis, AC005256.1 (estimated coefficient = −0.474), AC026336.3 (estimated coefficient = −0.030), AL161618.1 (estimated coefficient = −1.661), and BX322234.1 (estimated coefficient = 1.511) were used to construct a prognostic risk model. In the train set and test set, the risk model was shown to have both a high prognostic and a diagnostic value. Conclusion: We developed a novel GI-derived 4-lncRNA signature for the diagnosis and prognosis of patients with endometrial cancer. These findings offered a novel perspective in the clinical management of endometrial cancer.

Cationic polyacrylamide (CPAM) is a commonly used flocculant for water treatment. Factors that affect the flocculation effect and can be controlled manually include the type and dosage of CPAM, wastewater pH, stirring time and settling time, and their reasonable setting is critical to the flocculation effect of CPAM. In this paper, the optimal flocculation conditions of a novel CPAM were studied. First, single-factor tests were conducted to preliminarily explore the optimal range of factors that influence CPAM flocculation, and then response surface methodology (RSM) tests were performed to accurately determine the optimums of the influencing factors. The results showed that the flocculation effect was better when the intrinsic viscosity was larger or the cationic degree of CPAM was higher. The CPAM dosage, wastewater pH and stirring time significantly impacted the flocculation effect, and inflection points were observed. A model that could guide CPAM-8.14-40.2 flocculation was obtained by RSM tests. The model optimization showed that the optimal flocculation conditions of CPAM-8.14-40.2 for treating wastewater prepared with kaolin were as follows: the CPAM dosage, wastewater pH and stirring time were 5.83 mg·L−1, 7.28, and 5.95 min, respectively, and the turbidity of the treated wastewater was reduced to 6.24 NTU.

In this study, a brass or glass spherical impactor vertically penetrating into a granular bed composed of mono-sized spherical or elongated particles was simulated with three-dimensional (3D) discrete element method (DEM). Good agreement of the particle masses in the cup before and after penetration can be found in the simulations and experiments. The effects of particle length (Lp), friction coefficient, and particle configuration on the penetration depth of the impactor, ejecta mass, and solid volume fraction describing the response of the granular bed are discussed. The penetration depth is negatively correlated with Lp as the corresponding solid volume fraction of the granular bed decreases. A smaller friction coefficient leads to a larger penetration depth of the impactor and more ejection of particles. When the impactor is penetrating the Lp = 10 mm elongated particles, the penetration depth is negatively correlated to the order parameter and solid volume fraction.

Thorium-229 possesses the lowest first nuclear excited state, with an energy of approximately 8 eV. The extremely narrow linewidth of the first nuclear excited state, with an uncertainty of 53 THz, prevents direct laser excitation and realization of the nuclear clock. We present a proposal using the Coulomb crystal of a linear chain formed by $$^{229}$$ 229 Th$$^{3+}$$ 3 + ions, where the nuclei of $$^{229}$$ 229 Th$$^{3+}$$ 3 + ions in the ion trap are excited by the electronic bridge (EB) process. The 7$$P_{1/2}$$ P 1 / 2 state of the thorium-229 nuclear ground state is chosen for EB excitation. Using the two-level optical Bloch equation under experimental conditions, we calculate that 2 out of 36 prepared thorium ions in the Coulomb crystal can be excited to the first nuclear excited state, and it takes approximately 2 h to scan over an uncertainty of 0.22 eV. Taking advantage of the transition enhancement of EB and the long stability of the Coulomb crystal, the energy uncertainty of the first excited state can be limited to the order of 1 GHz.

Background Premium intraocular lenses (PIOLs), particularly those using multifocal, extended depth of focus (EDoF) and toric technologies, have been in clinical use for decades, giving countless cataract patients the ability to see the world clearly again. To explore the development process, research status and future development trends of PIOLs, we explored research on PIOLs from the past 22 years through bibliometrics. Methods The literature search was performed on the Web of Science and included PIOL studies published between 2000 and November 2022. The retrieved literature was collated and analyzed by R-tool's Bibliometrix package, CitNetExplorer, CiteSpace and other software. Results We obtained a total of 1801 articles about PIOLs, most of which were published in Spain and the United States. The organization that published the most articles was the University of Valencia in Spain. Alió JL, and Montés-Micó R, from Spain were the most influential authors in this field. The Journal of Cataract and Refractive Surgery and Journal of Refractive Surgery were the core journals for this field; the top 10 cited articles mainly focus on postoperative satisfaction with multifocal IOLs and postoperative results of toric IOLs. Through a key word analysis, we found that trifocal IOLs, astigmatism and EDoF IOLs are the most discussed topics at present, and the importance of astigmatism and the clinical application of the new generation of PIOL are the emerging research trends. In addition, we found that researchers are not only focusing on the application of cutting-edge technology but also paying increasing attention to patients' subjective satisfaction. Conclusion Bibliometric analysis can effectively help to identify multilevel concerns in premium intraocular lens (PIOL) research and we found that in the past 2 decades, the research of PIOL has made rapid development and gradually matured, countless cataract patients can regain excellent visual quality and improve their quality of life after surgery. The current research hotspots regarding PIOL are the application of EDoF IOL as well as trifocal IOL and its toric models and the development of new types of PIOLs.

The dust on indoor and outdoor surfaces of the window glasses were collected using sterile cotton balls in 11 cities from China. Two sampling campaigns were conducted with the time interval of 7 days to investigate the accumulation especially during the Spring festival holidays. Twenty-nine perfluoroalkyl acids (PFAA) were quantified to investigate concentration, composition, and toddlers' exposure. The concentrations of ∑PFAA ranged from no detection (nd) to 43 ng/m2 (mean 8.9 ± 10 ng/m2). Perfluorobutanoic acid (PFBA) was detected in 78% samples and accounted for 55 ± 21% of ∑PFAA concentrations. 6:2 fluorotelomer sulfonic acid (6:2 FTSA) and hexafluoropropylene oxide dimer acid (HFPO-DA) were detected in more than 50% samples indicating the use of alternatives. Fluorotelomer carboxylic acid (FTCA) and fluorotelomer unsaturated acid (FTUCA) were found in the dust, implying the degradation of fluorotelomer alcohols (FTOH). The highest concentration of ∑PFAA (43 ng/m2) was found in outdoor dust from Xinzhou, Shanxi Province. Higher ∑PFAA concentrations were found in indoor dust than outdoor in 6 paired samples (3 from Feb. 14 and 3 from Feb. 21). In Tianjin and Handan, the concentrations of ∑PFAA from outdoor surfaces were higher in sampling campaign I (SC I, Feb. 21) than in sampling campaign II (SC II, Feb. 14), implying intensive outdoor release. The exposure of 2-year-old toddlers to PFAA via hand-to-mouth ingestion and dermal absorption was estimated; the mean values of intake were 2.1 and 1.5 pg/kg body weight, respectively, assuming an exposure time of 1 h.

s Purpose To explore the distinct expression and diverse roles of IL-36 cytokines in dry eye disease using an in vitro hyperosmolarity model of human corneal epithelial cells (HCECs). Methods Primary HCECs were cultured from fresh donor limbal explants. Hyperosmolarity model was established by switching HCECs from isosmotic (312 mOsM) to hyperosmotic medium (350–500 mOsM) alone or with addition of rhIL-36RA or rhIL-38 for 2–48 h. Some cultures were treated with IL-36α (1–10 ng/ml) with or without rhIL-36RA or rhIL-38. Gene expression was detected by RT-qPCR; and protein production and barrier disruption were evaluated by ELISA and/or immunofluorescent staining. Results IL-36 cytokines were differential expressed in primary HCECs. Among 3 pro-inflammatory agonists, IL-36α, but not IL-36β and IL-36γ, was distinctly induced at osmolarity-dependent manner while two antagonist IL-36RA and IL-38 were significantly suppressed in HCECs exposed to hyperosmotic stress. IL-36α increased to 4.4-fold in mRNA and 6.9-fold at protein levels (116.0 ± 36.33 pg/ml vs 16.79 ± 6.51 pg/ml in controls) by 450 mOsM, but dramatically inhibited by addition of rhIL-36RA or rhIL-38. Exogenous rhIL-36α stimulated expression of TNF-α and IL-1β at mRNA and protein levels and disrupted tight junction proteins ZO-1 and occludin. However, rhIL-36RA or rhIL-38 suppressed TNF-α and IL-1β production and protected HCECs from barrier disruption in response to IL-36α or hyperosmolarity. Conclusions Our findings demonstrate that the stimulated pro-inflammatory IL-36α with the suppressed antagonists IL-36RA and IL-38 is a novel mechanism by which hyperosmolarity induces inflammation in dry eye. IL-36RA and IL-38 may have a therapeutic potential in dry eye.

Expanding the enzymatic toolbox for the green synthesis of valuable molecules is still of high interest in synthetic chemistry and the pharmaceutical industry. Chiral thiiranes are valuable sulfur-containing heterocyclic compounds, but relevant methods for their enantioselective synthesis are limited. Herein, we report a biocatalytic thionation strategy for the enantioselective synthesis of thiiranes, which was developed based on the halohydrin dehalogenase (HHDH)-catalyzed enantioselective ring-opening reaction of epoxides with thiocyanate and a subsequent nonenzymatic rearrangement process. A novel HHDH was identified and engineered for enantioselective biocatalytic thionation of various aryl- and alkyl-substituted epoxides on a preparative scale, affording the corresponding thiiranes in up to 43 % isolated yield and 98 % ee. Large-scale synthesis and useful transformations of chiral thiiranes were also performed to demonstrate the utility and scalability of the biocatalytic thionation strategy.

Background 5-Aminolevulinic acid (ALA) recently received much attention due to its potential application in many fields. In this study, an ALA production strain of Escherichia coli was constructed by rational metabolic engineering and stepwise improvement based on known regulatory and metabolic information and CRISPR/Cas9 mediated gene knockout. Results A metabolic strategy to produce ALA directly from glucose in this recombinant E. coli via the C5 pathway was applied herein. The rational metabolic engineering by gene knockouts significantly improved ALA production from 662.3 to 1601.7 mg/L. In addition, we managed to synergistically produce ALA via the C4 pathway in recombinant strain. The expression of a modified hemA gene, encoding an ALA synthase from Rhodobacter sphaeroides, improved ALA production from 1601.7 to 2099.7 mg/L. After 24 h cultivation, a yield of 0.210 g ALA per g glucose was achieved by constructed E. coli D5:FYABD-RSA. Conclusion Our study revealed that an industrially competitive strain can be efficiently developed by metabolic engineering based on combined rational modification and optimization of gene expression.

Rechargeable aluminum-ion batteries have attracted increasing attention owing to the advantageous multivalent ion storage mechanism thus high theoretical capacity as well as inherent safety and low cost of using aluminum. However, their development has been largely impeded by the lack of suitable positive electrodes to provide both sufficient energy density and satisfactory rate capability. Here we report a candidate positive electrode based on ternary metal oxides, Fe

We consider the classic cake cutting problem where one allocates a divisible cake to n participating agents. Among all valid divisions, fairness and efficiency (a.k.a. ~social welfare) are the most critical criteria to satisfy and optimize, respectively. We study computational complexity of computing an efficiency optimal division given the conditions that the allocation satisfies proportional fairness and assigns each agent a connected piece. For linear valuation functions, we give a polynomial time approximation scheme to compute an efficiency optimal allocation. On the other hand, we show that the problem is NP-hard to approximate within a factor of Ω 1/√n for general piecewise constant functions, and is NP-hard to compute for normalized functions.

Linguistic coherence—the co-variation of language variants within speaker repertoires—has been proposed as a key process driving the divergence of language dialects. Previous studies on coherence have been often limited by dataset sizes and analyses. We analyze the use of 185 variables across 78 speakers from the Gurindji community in Australia. We use two multivariate statistical approaches to test whether clusters of variables co-vary with generation, family, household, exposure to Gurindji language speakers and education. Using Discriminant Correspondence Analysis, we find generation is the strongest grouping factor of speakers and co-varies with clusters of variants. Using the Generalized Linear Mixed Model, we find these clusters of variants not only represent a gradual loss of Gurindji language use across generations, but also contribute to distinct patterns of language usage in the different generations. Our study demonstrates the use of multivariate analyses on big datasets to identify sociolects, an important step in linking the ‘micro-level’ processes to the ‘macro-level’ outcomes.

It well known that vehicle detection is an important component of the field of object detection. However, the environment of vehicle detection is particularly sophisticated in practical processes. It is comparatively difficult to detect vehicles of various scales in traffic scene images, because the vehicles partially obscured by green belts, roadblocks or other vehicles, as well as influence of some low illumination weather. In this paper, we present a model based on Faster R–CNN with NAS optimization and feature enrichment to realize the effective detection of multi-scale vehicle targets in traffic scenes. First, we proposed a Retinex-based image adaptive correction algorithm (RIAC) to enhance the traffic images in the dataset to reduce the influence of shadow and illumination, and improve the image quality. Second, in order to improve the feature expression of the backbone network, we conducted Neural Architecture Search (NAS) on the backbone network used for feature extraction of Faster R–CNN to generate the optimal cross-layer connection to extract multi-layer features more effectively. Third, we used the object Feature Enrichment that combines the multi-layer feature information and the context information of the last layer after cross-layer connection to enrich the information of vehicle targets, and improve the robustness of the model for challenging targets such as small scale and severe occlusion. In the implementation of the model, K-means clustering algorithm was used to select the suitable anchor size for our dataset to improve the convergence speed of the model. Our model has been trained and tested on the UN-DETRAC dataset, and the obtained results indicate that our method has art-of-state detection performance.

Cohesive elongated particles are ubiquitous in some industrial particle and powder processing operations; however, only a few studies investigated the kinematics of such particles using a discrete element method (DEM). Therefore, in this study, a DEM-based model was used to investigate the kinematics of cohesive elongated particles agitated in a vertical axis mixer. A contact-area-proportional model accounting for sphero-cylindrical particle geometry was employed for modeling particle–particle and particle–boundary cohesion. Generally, the flow patterns of the elongated particles in the vertical axis mixer remain stable as the particle cohesion level increases from no cohesion to low cohesion. However, flow pattern differences appear when the particle cohesion level increases to high cohesion, including the formation of large agglomerates, particle adhesion to the drum base and sidewall, and a significant heap height increase owing to the large angle of repose which high cohesion particles could maintain. Overall increasing the particle cohesion level increases the mass flow rate of particles over the blade, emphasizing the importance of particle cohesion of the bed. At the condition of high cohesion, the variation of the flow rate over the blade is significantly higher than that for no cohesion or low cohesion.

Intramuscularly injectable long-acting prodrug-based microcrystals (MCs) are of particular interest for chronic disease management. Nevertheless, current prevalently used linkers degraded by enzymes have the potential drawback of substantial differences in enzyme levels between individuals. Here, we reported the synthesis of a stearyl-modified paliperidone prodrug (SKP) with an acid-sensitive ketal linker for developing long-acting MC antipsychotics. SKP-MCs of three different sizes were prepared and systematically examined. We found that paliperidone exposure in SKP-MC-treated rats was prolonged compared with that in rats treated with the commercial antipsychotic Invega Sustenna and that the drug release rate decreased with increasing MC size. In inflammation-inhibition-model rats, paliperidone release from the SKP-MCs was considerably decreased, indicating that the immune-mediated foreign-body response after intramuscular administration boosted paliperidone release. Our findings will provide valuable insights into in vivo drug release from prodrug-based MC formulations. The ketal-linked prodrug strategy might be a new solution for developing long-acting prodrug formulations of hydroxyl-group-bearing drugs.

Spatial alignment is a key feature in the design of the straddle-type monorail system (STM), which greatly affects the dynamic characteristics of the STM system. Considering the shear and torsional deformation of the track beam, a new coupling dynamic model of the STM system is established to investigate the dynamic characteristics under spatial alignment. The running safety and the vibration stability of the STM system under different spatial alignments are studied, and the optimal distance between the slope-changing point and the straight-slowing point is determined. Results show that the running safety and vibration stability indices increase when the curve radius decreases and the longitudinal slope gradient soars, and the vibration response of the vehicle is more obvious when the slope-changing points coincide with the transition curve of the track beam compared with that the straight-slowing points do not coincide with the slope-changing points. From the view of running safety and vibration stability, the slope-changing points should not coincide with the transition curve of the track beam, especially with the straight-slowing points. The proposed method can be adopted in the safety design and vibration control of the STM system.

Oxygen, as a terminal electron acceptor, is an essential substrate in the aerobic bio-oxidation process, affecting bacterial vitality and bio-oxidation performance. In this study, a new and smart platform biotechnology of sealed-oxygen supply bioreactor (SOS-BR) was developed by improving gas pressure to significantly intensify oxygen transfer rate and resolving the formidable barriers of aerobic catalysis. In virtue of SOS-BR, the bio-productivity was greatly improved for three representative substrates (xylose, furfural, glycerol) bio-oxidation with the whole-cell catalysis of Gluconobacter oxydans. The determination of oxygen transfer coefficient (KLα) established an upgraded theoretical dynamic model for gas pressure intersification biosystem. Additionally, viscosity measurement and combined pressure control strategy explained the inflection point phenomenon of productivity and confirmed the intensify mechanism. The new strategy of significantly intensifying oxygen transfer provided insightful ideas for overcoming the subbon obstacle of obligate aerobic catalysis, and further promoted industrial practicability of bio-oxidation.

Corticosteroids have for some time been used as first-line drugs for the topical treatment of noninfectious uveitis, but poor ocular bioavailability and the rapid clearance of eye drops necessitate frequent dosing, reducing patient compliance. In this study, we used an acid-sensitive stearoxyl-ketal-dexamethasone pro-drug microcrystals (SKD MCs), which is consistently safe and effective in the control of uveitis inflammation in rats. We used a rat model of experimental autoimmune uveitis (EAU) to evaluate the effects of SKD MCs in terms of clinical manifestations, molecular biology, pathological histology, and visual electrophysiology compared to dexamethasone sodium phosphate injection or phosphate-buffered saline. SKD MCs significantly reduced inflammation in EAU, improved the ability to suppress inflammatory cytokines and to protect retinal function, and significantly reduced retinal microglia activation, with no increase in intraocular pressure throughout the treatment. Our results indicate that the SKD MCs formulation holds promise as a new strategy for the treatment of noninfectious uveitis and potentially other ocular inflammatory diseases.

Diabetic retinopathy (DR) is one of the most common complications of diabetes and major cause of blindness among people over 50 years old. Current studies showed that the vascular endothelial growth factor (VEGF) played a central role in the pathogenesis of DR, and application of anti-VEGF has been widely acknowledged in treatment of DR targeting retinal neovascularization. However, anti-VEGF therapy has several limitations such as drug resistance. It is essential to develop new drugs for future clinical practice. The vitreous takes up 80% of the whole globe volume and is in direct contact with the retina, making it possible to explore the pathogenesis of DR by studying related factors in the vitreous. This article reviewed recent studies on DR-related factors in the vitreous, elaborating the VEGF upstream hypoxia-inducible factor (HIF) pathway and downstream pathways phosphatidylinositol diphosphate (PIP2), phosphoinositide-3-kinase (PI3K), and mitogen-activated protein kinase (MAPK) pathways. Moreover, factors other than VEGF contributing to the pathogenesis of DR in the vitreous were also summarized, which included factors in four major systems, kallikrein-kinin system such as bradykinin, plasma kallikrein, and coagulation factor XII, oxidative stress system such as lipid peroxide, and superoxide dismutase, inflammation-related factors such as interleukin-1β/6/13/37, and interferon-γ, matrix metalloproteinase (MMP) system such as MMP-9/14. Additionally, we also introduced other DR-related factors such as adiponectin, certain specific amino acids, non-coding RNA and renin (pro) receptor in separate studies.