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Objectives: Autonomic nervous activity imbalance plays an important role in atrial fibrillation (AF). AF can be treated by acupuncture at the Neiguan point (PC6), but the mechanism remains elusive. Here, we investigated autonomic nervous system activity in electroacupuncture (EA) at PC6 in a rat AF model., Material and Methods: In this study, we established a rat AF model via tail vein injection with ACh-CaCl 2 for ten consecutive days with or without EA at PC6. AF inducibility and heart rate variability (HRV) were assessed by electrocardiogram. Next, we completed in vivo recording of the activity of cervical sympathetic and vagal nerves, respectively. Finally, the activities of brain regions related to autonomic nerve regulation were assessed by c-Fos immunofluorescence and multichannel recording., Results: EA at PC6 decreased AF inducibility and prevented changes in HRV caused by ACh-CaCl 2 injection. Meanwhile, EA at PC6 reversed the increased sympathetic and decreased vagal nerve activity in AF rats. Furthermore, EA treatment downregulated increased c-Fos expression in brain regions, including paraventricular nucleus, rostral ventrolateral medulla, and dorsal motor nucleus of the vagus in AF, while c-Fos expression in nucleus ambiguus was upregulated with EA., Conclusion: The protective effect of EA at PC6 on AF is associated with balance between sympathetic and vagal nerve activities., Competing Interests: Conflict of Interest The authors reported no conflict of interest., (Copyright © 2022 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.)

Lishu County, which is located in the black soil region of Northeast China, represents a key site for the analysis of soil erosion intensity. This study offers a scientific foundation for the development of targeted soil and water conservation strategies within the region. The Revised Universal Soil Loss Equation (RUSLE) was employed to compute the soil erosion modulus in Lishu County, with the objective of conducting a quantitative analysis of the temporal and spatial distribution patterns of soil erosion. Additionally, the changing characteristics of soil erosion were examined from the perspectives of land use types and slope variations. The Generalized Connectivity Causality Model (GCCM) was utilized to identify the causal relationship between soil erosion and land use types through the reconstruction of state space and cross-mapping predictions. (1) Soil erosion in Lishu County between 2000 and 2020 predominantly exhibited mild to moderate levels, characterized by patchy and sporadic erosion, with relatively severe occurrences in the northern and central regions. (2) Soil erosion was correlated with land use and slope variations, with more than 90% of erosion incidents transpiring in cultivated land areas. The 3°-5° slope range in Lishu County emerged as a focal point for erosion, necessitating targeted prevention and control measures. (3) The GCCM model illustrated a discernible causal relationship between soil erosion and land use, revealing mutual influences between the two factors. Between 2000 and 2020, both the area and intensity of soil erosion in Lishu County exhibited an initial increase, followed by a subsequent decrease. This suggests an overall trend of amelioration in soil erosion conditions. However, notable spatial disparities persist in the erosion distribution across the region., (© 2024. The Author(s).)

Endoscopic optical coherence tomography (OCT) is widely used in the detection of morphological alterations in luminal organs, which provides high-resolution, three-dimensional (3D) images of internal tissues. In most cases, lesions are revealed early by microvascular pathological changes in cavity tissues. There is a significant demand for the performance of endoscopic OCT angiography (OCTA) to visualize the superficial capillaries. Proximal catheters have attracted widespread attention due to the advantages of small size and low cost. However, in comparison with the OCT system using distal catheters, low rotation speed and poor stability of the proximal scanning OCT prolonged its absence of endoscopic OCTA in common commercial and lab systems. In this paper, endoscopic OCTA was realized in the proximal scanning endoscopic OCT system by calculating decorrelation between adjacent B-scan images in the continuous rotation and retraction scheme. A precision registration algorithm was proposed to guarantee the quality of the OCTA image. The feasibility of the endoscopic OCTA was validated using a microfluidic phantom. In vivo studies were performed in the rat rectum, visualizing the intricate microvascular architecture, specifically within the submucosal capillaries. To the best of our knowledge, the first implementation of endoscopic OCTA was achieved under a continuous spiral B-scan rotation scheme in a proximally controlled OCT system, facilitating visualization of blood flow within narrow lumen tissues.

In recent years, researchers have taken the many-objective optimization algorithm, which can optimize 5, 8, 10, 15, 20 objective functions simultaneously, as a new research topic. However, the current research on many-objective optimization technology also encounters some challenges. For example: Pareto resistance phenomenon, difficult diversity maintenance. Based on the above problems, this paper proposes a many-objective evolutionary algorithm based on three states (MOEA/TS). Firstly, a feature extraction operator is proposed. It can extract the features of the high-quality solution set, and then assist the evolution of the current individual. Secondly, based on Pareto front layer, the concept of "individual importance degree" is proposed. The importance degree of an individual can reflect the importance of the individual in the same Pareto front layer, so as to further distinguish the advantages and disadvantages of different individuals in the same front layer. Then, a repulsion field method is proposed. The diversity of the population in the objective space is maintained by the repulsion field, so that the population can be evenly distributed on the real Pareto front. Finally, a new concurrent algorithm framework is designed. In the algorithm framework, the algorithm is divided into three states, and each state focuses on a specific task. The population can switch freely among these three states according to its own evolution. The MOEA/TS algorithm is compared with 7 advanced many-objective optimization algorithms. The experimental results show that the MOEA/TS algorithm is more competitive in many-objective optimization problems., (© 2024. The Author(s).)

Two-photon microscopy (TPM) has a wide range of applications in the biomedical field. Two-photon multi-focus microscopy (TPMM) greatly improves the imaging speed by combining TPM with multi-focus technology. Therefore, TPMM based on spatial light modulator (SLM) has greater advantages in generating multi-focus point (MFP) with uniform intensity and flexible position than to other schemes. However, the zero-order beam (ZOB) produced by SLM in TPMM causes imperfection of the imaging system. For example, some sample areas are scanned repeatedly or illuminated unexpectedly. In this article, we proposed a TPMM system with improved performance by eliminating the ZOB. Apart from the target MFP, we utilize a phase-only SLM to generate another corrective beam (CB) with controllable amplitude, phase, and position precisely. The CB can produce destructive interference completely with the ZOB generated by the dead areas of the SLM. The method has a larger field of view, higher efficiency, and better uniformity in generating MFP compared to the method of overlaying the blaze grating. Simulations and experiments demonstrate the advantages of this approach.

Chemodynamic therapy (CDT), employing metal ions to transform endogenous H 2 O 2 into lethal hydroxyl radicals ( • OH), has emerged as an effective approach for tumor treatment. Yet, its efficacy is diminished by glutathione (GSH), commonly overexpressed in tumors. Herein, a breakthrough strategy involving extracellular vesicle (EV) mimetic nanovesicles (NVs) encapsulating iron oxide nanoparticles (IONPs) and β-Lapachone (Lapa) was developed to amplify intracellular oxidative stress. The combination, NV-IONP-Lapa, created through a serial extrusion from ovarian epithelial cells showed excellent biocompatibility and leveraged magnetic guidance to enhance endocytosis in ovarian cancer cells, resulting in selective H 2 O 2 generation through Lapa catalysis by NADPH quinone oxidoreductase 1 (NQO1). Meanwhile, the iron released from IONPs ionization under acidic conditions triggered the conversion of H 2 O 2 into • OH by the Fenton reaction. Additionally, the catalysis process of Lapa eliminated GSH in tumor, further amplifying oxidative stress. The designed NV-IONP-Lapa demonstrated exceptional tumor targeting, facilitating MR imaging, and enhanced tumor suppression without significant side effects. This study presents a promising NV-based drug delivery system for exploiting CDT against NQO1-overexpressing tumors by augmenting intratumoral oxidative stress.

Solving the distorted wavefront in wavefront sensorless adaptive optics (WFSL-AO) relies on excellent optimizers. Many local or global optimization algorithms have been applied to WFSL-AO; however, there is still a challenge to balance the effect and speed of correcting aberrations. To overcome this, a novel global optimization algorithm named asymptotic proximal point (APP) method is introduced into WFSL-AO in this Letter. We compare this algorithm with the various existing optimization algorithms in convergence speed and correction capability by performing numerical simulations. The results show that the APP method beats all competitors with a better correction effect and faster speed.

Quantitative analysis of optical attenuation based on optical coherence tomography images will offer an effective method to enhance diagnostic capabilities. In this paper, the optical attenuation in demineralized caries specimens was calculated to distinguish between normal teeth and carious teeth and further to differentiate the severity of caries, and thus come to the half-automated diagnosis of dental caries. Results show that the attenuation coefficient in carious regions is approximately 4.97 mm - 1 ± 0.206 , while that of normal teeth is about 3.69 mm - 1 ± 0.231 . Attenuation coefficient of carious regions is 35% higher than that of normal teeth. Moreover, five classes of caries were qualified and classified based on the optical attenuation coefficient. Compared with the healthy teeth, there is a noticeable disparity in the attenuation coefficients of carious teeth, both on the surface and at the dentinoenamel junction. This study provides a method for accurate caries diagnosis, particularly in detection of early lesions and subtle structural changes., (© 2024 Wiley‐VCH GmbH.)

Hypoxia is a globally pressing environmental problem in aquatic ecosystems. In the present study, a comprehensive analysis was performed to evaluate the effects of hypoxia on physiological responses (hematology, cortisol, biochemistry, hif gene expression and the HIF pathway) of hybrid sturgeons ( Acipenser schrenckii ♂ × Acipenser baerii ♀). A total of 180 hybrid sturgeon adults were exposed to dissolved oxygen (DO) levels of 7.00 ± 0.2 mg/L (control, N), 3.5 ± 0.2 mg/L (moderate hypoxia, MH) or 1.00 ± 0.1 mg/L (severe hypoxia, SH) and were sampled at 1 h, 6 h and 24 h after hypoxia. The results showed that the red blood cell (RBC) counts and the hemoglobin (HGB) concentration were significantly increased 6 h and 24 h after hypoxia in the SH group. The serum cortisol concentrations gradually increased with the decrease in the DO levels. Moreover, several serum biochemical parameters (AST, AKP, HBDB, LDH, GLU, TP and T-Bil) were significantly altered at 24 h in the SH group. The HIFs are transcription activators that function as master regulators in hypoxia. In this study, a complete set of six hif genes were identified and characterized in hybrid sturgeon for the first time. After hypoxia, five out of six sturgeon hif genes were significantly differentially expressed in gills, especially hif-1α and hif-3α, with more than 20-fold changes, suggesting their important roles in adaptation to hypoxia in hybrid sturgeon. A meta-analysis indicated that the HIF pathway, a major pathway for adaptation to hypoxic environments, was activated in the liver of the hybrid sturgeon 24 h after the hypoxia challenge. Our study demonstrated that hypoxia, particularly severe hypoxia (1.00 ± 0.1 mg/L), could cause considerable stress for the hybrid sturgeon. These results shed light on their adaptive mechanisms and potential biomarkers for hypoxia tolerance, aiding in aquaculture and conservation efforts.

Lonicera macranthoides , the main source of traditional Chinese medicine Lonicerae Flos, is extensively cultivated in Southwest China. However, the quality of L. macranthoides produced in this region significantly varies due to its wide distribution and various cultivation breeds. Herein, 50 Lonicerae Flos samples derived from different breeds of L. macranthoides cultivated in Southwest China were collected for quality evaluation. Six organic acids and three saponin compounds were quantitatively analyzed using HPLC. Furthermore, the antioxidant activity of a portion of samples was conducted with 2,2'-Azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS) and 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radical scavenging experiments. According to the quantitative results, all samples met the quality standards outlined in the Chinese Pharmacopoeia. The samples from Guizhou, whether derived from unopened or open wild-type breeds, exhibited high quality, while the wild-type samples showed relatively significant fluctuation in quality. The samples from Chongqing and Hunan demonstrated similar quality, whereas those from Sichuan exhibited relatively lower quality. These samples demonstrated significant abilities in clearing ABTS and DPPH radicals. The relationship between HPLC chromatograms and antioxidant activity, as elucidated by multivariate analysis, indicated that chlorogenic acid, isochlorogenic acid A, isochlorogenic acid B, and isochlorogenic acid C are active components and can serve as Q-markers for quality evaluation.

Magnetic separation of photocatalysts holds great promise for water treatment. A magnetic separation method has a positive effect on the recovery of catalysts after degradation. In this paper, an efficient and reusable catalytic system is developed based on coating magnetic Fe 3 O 4 by depositing Fe 2+ on the surface of ZnO. The Fe 3 O 4 /ZnO nanocomposite exhibits enhanced performance for organic pollutant degradation. The Fe 3 O 4 /ZnO system demonstrates a high photocatalytic activity of 100% degradation efficiency in Rhodamine B (RhB) degradation under UV light irradiation for 50 min. The excellent photocatalytic activity is primarily due to the separation of photogenerated electron-hole pairs being facilitated by the strong interaction between Fe 3 O 4 and ZnO. The induction of the magnetic Fe 3 O 4 endows the Fe 3 O 4 /ZnO composite with superior magnetic separation capability from water. Experiments with different radical scavengers revealed that the hydroxyl radical (·OH) is the key reactive radical for the effective degradation of RhB. This work innovatively affords a common interfacial dopant deposition strategy for catalytic application in the degradation of organic dye pollutants and catalyst separation from wastewater efficiently.

Purpose: Guselkumab is a highly effective biologic agent for treating psoriasis. This study aimed to explore potential transcription factors involved in psoriasis pathogenesis and response to guselkumab treatment, aiming to provide new therapeutic strategies for psoriasis., Patients and Methods: We analyzed gene expression and single-cell RNA-seq data from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) that upregulated in psoriasis and downregulated after guselkumab treatment were subjected to enrichment analyses. Single-cell regulatory network inference and clustering (SENIC) and regulon module analyses identified different regulon activities between the lesion and non-lesion skin of psoriasis. Cell-cell communication analysis revealed interactions among specific cell clusters. Transcription factor (TF) regulons were identified from the guselkumab-specific regulon network. Gene set enrichment analysis (GSEA) confirmed the IRF7 regulon in the validation cohort. Finally, the expression level of IRF7 was identified in plaque psoriasis before and after 12 weeks of guselkumab therapy by immunohistochemical experiment., Results: 799 DEGs were downregulated after guselkumab treatment. Enrichment analyses highlighted the interleukin-17 (IL-17) pathway in this gene set. The M2 module exhibited the primary difference in regulon activity. Strong cell-cell interactions were observed between keratinocytes and immune cells. IRF7 regulon had significant roles in psoriasis and treatment response, as validated by GSEA analysis using the IL-17 signaling pathway as a reference. The immunohistochemical analysis unveiled substantial differences in the expression levels of IRF7 in psoriatic skin samples before and after 12 weeks of guselkumab treatment., Conclusion: IRF7 may be the key player in psoriasis pathogenesis and the therapeutic process involving guselkumab. Targeting IRF7 might offer new therapeutic strategies for psoriasis., Competing Interests: The authors declare no competing interests related to this study., (© 2024 Yuan et al.)

Nucleotide biosynthesis encompasses both de novo and salvage synthesis pathways, each characterized by significant material and procedural distinctions. Despite these differences, cells with elevated nucleotide demands exhibit a preference for the more intricate de novo synthesis pathway, intricately linked to modes of enzyme regulation. In this study, we primarily scrutinize the biological importance of a conserved yet promising mode of enzyme regulation in nucleotide metabolism-cytoophidia. Cytoophidia, comprising cytidine triphosphate synthase or inosine monophosphate dehydrogenase, is explored across diverse biological models, including yeasts, Drosophila, mice, and human cancer cell lines. Additionally, we delineate potential biomedical applications of cytoophidia. As our understanding of cytoophidia deepens, the roles of enzyme compartmentalization and polymerization in various biochemical processes will unveil, promising profound impacts on both research and the treatment of metabolism-related diseases., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Previous studies have found that removing the sporoderm significantly enhanced antitumor and immunoregulatory activities of Ganoderma lucidum spore (GLS) compared with breaking the sporoderm. However, the pharmacokinetics of sporoderm-removed GLS (RGLS) and sporoderm-broken GLS (BGLS) remain elusive. To compare the pharmacokinetic differences between the two products, we developed a UPLC-QqQ MS method for determining nine representative triterpenoid concentrations. Chloramphenicol was used as an internal standard. The samples were separated on a reversed-phase column using acetonitrile-0.1% formic acid and water-0.1% formic acid as mobile phases. Nine triterpenoids were analyzed using multiple reaction monitoring mode. The results showed that the area under the concentration-time curve from dosing to time t of all nine components was increased in RGLS compared with BGLS. And the time to the maximum concentration in BGLS was delayed compared with that of RGLS. These indicated that the absorption of RGLS was better than that of BGLS, and the sporoderm might hinder the absorption of the active components. These results increase our understanding of the bioavailability of BGLS and RGLS and indicate that increased bioavailability is one of the main reasons for the enhanced efficacy of RGLS., (© 2023 John Wiley & Sons, Ltd.)

Aim: To develop nanocarriers for targeting the delivery of chemotherapeutics to overcome multidrug-resistant ovarian cancer. Materials & methods: Doxorubicin-loaded nanovesicles were obtained through serial extrusion, followed by loading of P-glycoprotein siRNA and folic acid. The targeting ability and anticancer efficacy of the nanovesicles were evaluated. Results: The doxorubicin-loaded nanovesicles showed a high production yield. The presence of P-glycoprotein siRNA and folic acid resulted in reversed drug resistance and tumor targeting. This nanoplatform tremendously inhibited the viability of multidrug-resistant ovarian cancer cells, which was able to target tumor tissue and suppress tumor growth without adverse effects. Conclusion: These bioengineered nanovesicles could serve as novel extracellular vesicles mimetics for chemotherapeutics delivery to overcome multidrug resistance.

ABSTRACT The main protease (3-chymotrypsin-like protease, 3CLpro) of SARS-CoV-2 has become a focus of anti-coronavirus research. Despite efforts, drug development targeting 3CLpro has been hampered by limitations in the currently available activity assays. Additionally, the emergence of 3CLpro mutations in circulating SARS-CoV-2 variants has raised concerns about potential resistance. Both emphasize the need for a more reliable, sensitive, and facile 3CLpro assay. Here, we report an orthogonal dual reporter-based gain-of-signal assay for measuring 3CLpro activity in living cells. It builds on the finding that 3CLpro induces cytotoxicity and reporter expression suppression, which can be rescued by its inhibitor or mutation. This assay circumvents most limitations in previously reported assays, especially false positives caused by nonspecific compounds and signal interference from test compounds. It is also convenient and robust for high throughput screening of compounds and comparing the drug susceptibilities of mutants. Using this assay, we screened 1789 compounds, including natural products and protease inhibitors, with 45 compounds that have been reported to inhibit SARS-CoV-2 3CLpro among them. Except for the approved drug PF-07321332, only five of these inhibit 3CLpro in our assays: GC376; PF-00835231; S-217622; Boceprevir; and Z-FA-FMK. The susceptibilities of seven 3CLpro mutants prevalent in circulating variants to PF-07321332, S-217622, and GC376 were also assessed. Three mutants were identified as being less susceptible to PF-07321322 (P132H) and S-217622 (G15S, T21I). This assay should greatly facilitate the development of novel 3CLpro-targeted drugs and the monitoring of the susceptibility of emerging SARS-CoV-2 variants to 3CLpro inhibitors.

Background: The clinical applications of dispensing granules (DG) have increased dramatically. However, it is controversial whether the DG has the same quality and efficacy compared with traditional decoction (TD). In this study, the contents of main compounds, hypoglycemic effects, and potential mechanism of Coptidis Rhizoma (CR) and Scutellaria-coptis (SC), constituted of a 1:1 mixture of CR and Scutellariae Radix (SR), in the forms of TD and DG were compared., Methods: The quantitative analysis was performed on an UPLC-PDA method. The 6-weeks-old male db/db mice were used as Type 2 Diabetes Mellitus (T2DM) mouse modle to investigate the antidiabetic effects of CR and SC in TD form (CR TD and SC TD), as well as CR and SC in DG form (CR DG and SC DG)., Results: The total content of five alkaloids in CR TD ranged from 71.00 to 78.62 mg, whereas in CR DG it ranged from 38.77 to 53.68 mg in CR DG per 1 g of decoction pieces. Compared to CR TD, CR DG exhibited a 36% reduction on average. For SC samples, the precipitation occurred in the processing of TD but not in the DG, and the relative ratio of alkaloids to flavonoids was determined to be 1:1 in TD and 1:2 in DG. Furthermore, the animal experiments showed that the CR DG (equivalent to 3 g decoction pieces/kg) had almost the same hypoglycemic effect as CR TD when they were administered for 6 weeks. Compared with SC DG (equivalent to 6 g decoction pieces/kg), SC TD showed a better trend in ameliorating T2DM via ameliorating pancreatic structure and function, and activating Akt/AMPK/GLUT4 signaling pathways., Conclusion: This study indicated that the contents of main compounds were generally higher in CR TD than CR DG originated from the same raw materials. Additionally, changes in the contents of the primary components validated that the compound interactions are exclusive to SC TD during co-decoction, rather than SC DG. The disparate prossing of SC DG and SC TD caused differences both in chemical composition and hypoglycemic effect, suggesting that the substitutability of DG and TD requires further research., (© 2023. The Author(s).)

In 2020, Changchun Observatory developed a 280 mm wide-field optical telescope array to improve surveillance of space debris in the geosynchronous belt. There are many advantages including a wide field of view, the ability to observe a large area of sky and high reliability. However, the wide field of view causes a significant number of background stars to appear in the image when photographing space objects, making it difficult to detect them. This research focuses on the precise detection of GEO space objects from images taken by this telescope array in order to position them in large quantities. Our work further investigates the motion feature of an object, namely that the object can be seen as being in a uniform linear motion for a brief length of time. Based on this feature, the belt can be divided into a number of smaller areas and the telescope array scans each smaller area one at a time from east to west. To detect objects in the subarea, a combination of image differencing with trajectory association is used. The image differencing algorithm is used to remove most stars and screen out suspected objects in the image. Next, the trajectory association algorithm is employed to further filter out the real objects among the suspected ones, and the trajectories attributed to the same object are linked. The feasibility and accuracy of the approach were verified by the experiment results. The accuracy rate of trajectory association exceeds 90% and on average, more than 580 space objects can be detected per observation night. Since the J2000.0 equatorial system can accurately describe the apparent position of an object, the object can be detected by using this coordinate system as opposed to the pixel coordinate system.

Background: Metabolic hypertension (MH) has become the most common type of hypertension in recent years due to unhealthy eating habits and lifestyles of people, such as over-eating alcohol, high fat, and sugar diets (ACHFSDs). Therefore, effective means to combat MH are needed. Previous studies have shown that Panax notoginseng (Burkill) F. H. Chen flower saponins (PNFS) can lower blood pressure in spontaneously hypertensive rats (SHR). However, whether it acts on MH and its mechanism of action remain unclear.  METHODS: The pharmacodynamic effects of PNFS were evaluated in rats with ACHFSDs-induced MH. The blood pressure, blood biochemical, grip strength, face temperature, vertigo time, and liver index were estimated. The histological changes in the liver and aorta were observed using hematoxylin and eosin staining. The levels of ET-1, TXB 2 , NO, PGI 2 , Renin, ACE, Ang II, and ALD in plasma were detected using ELISA. The levels of C3, KLF5, LXRα, and Renin in kidney tissues were measured using qRT-PCR.The expression levels of C3, KLF5, LXRα, and Renin in kidney tissues were examined using Western blotting., Results: In the present study, PNFS was found to reduce blood pressure, face temperature, and vertigo time, increase grip strength and improve dyslipidemia in rats with MH. In addition, PNFS decreased the plasma levels of ET-1 and TXB 2 , elevated the levels of NO and PGI 2 , and improved pathological aortic injury. Meanwhile, PNFS decreased the plasma levels of Renin, ACE, Ang II, and ALD. QRT-PCR and Western bolt showed that PNFS downregulated C3, KLF5, LXRα, and Renin protein and mRNA expression in the kidneys of rats with MH., Conclusion: The finding of the present study suggested that PNFS could downregulate C3 and KLF-5 expression in rats with MH, thereby inhibiting the overactivation of the renin-angiotensin-aldosterone system, while improving vascular endothelial function and ultimately reducing blood pressure in rats with MH., (© 2023. The Author(s).)

Infectious hematopoietic necrosis virus (IHNV) is the most important pathogen threatening the aquaculture of salmonid fish in China. In addition to the common genogroup J IHNV, genogroup U has been newly discovered in China. However, there is no effective DNA vaccine to fight against this emerging genogroup U IHNV in China. In this study, DNA vaccines encoding the IHNV viral glycoprotein (G) gene of the GS2014 (genogroup J) and BjLL (genogroup U) strains isolated from northern China were successfully developed, which were identified by restriction analysis and IFA. The expression of the Mx-1 gene and G gene in the spleens and muscles of the injection site as well as the titers of the serum antibodies were measured to evaluate the vaccine efficacy by RT-qPCR and ELISA. We found that DNA vaccine immunization could activate Mx1 gene expression and upregulate G gene expression, and the mRNA levels of the Mx1 gene in the muscles were significantly higher than those in the spleens. Notably, DNA vaccine immunization might not promote the serum antibody in fish at the early stage of immunization. Furthermore, the efficacy of the constructed vaccines was tested in intra- and cross-genogroup challenges by a viral challenge in vivo. It seemed that the DNA vaccines were able to provide great immune protection against IHNV infection. In addition, the genogroup J IHNV-G DNA vaccine showed better immune efficacy than the genogroup U IHNV-G or divalent vaccine, which could provide cross-immune protection against the genogroup U IHNV challenge. Therefore, this is the first study to construct an IHNV DNA vaccine using the G gene from an emerging genogroup U IHNV strain in China. The results provide great insight into the advances of new prophylactic strategies to fight both the genogroup J and U IHNV in China.

The human coronavirus OC43 (HCoV-OC43) is one of the most common causes of common cold but can lead to fatal pneumonia in children and elderly. However, the available animal models of HCoV-OC43 did not show respiratory symptoms that are insufficient to assist in screening antiviral agents for respiratory diseases. In this study, we adapted the HCoV-OC43 VR-1558 strain by serial passage in suckling C57BL/6 mice and the resulting mouse-adapted virus at passage 9 (P9) contained 8 coding mutations in polyprotein 1ab, spike (S) protein, and nucleocapsid (N) protein. Pups infected with the P9 virus significantly lost body weight and died within 5 dpi. In cerebral and pulmonary tissues, the P9 virus replication induced the production of G-CSF, IFN-γ, IL-6, CXCL1, MCP-1, MIP-1α, RANTES, IP-10, MIP-1β, and TNF-α, as well as pathological alterations including reduction of neuronal cells and typical symptoms of viral pneumonia. We found that the treatment of arbidol hydrochloride (ARB) or Qingwenjiere Mixture (QJM) efficiently improved the symptoms and decreased n gene expression, inflammatory response, and pathological changes. Furthermore, treating with QJM or ARB raised the P9-infected mice's survival rate within a 15 day observation period. These findings suggested that the new mouse-adapted HCoV-OC43 model is applicable and reproducible for antiviral studies of HCoV-OC43., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xie, Fang, Baloch, Yu, Zhao, Li, Zhang, Li, Zhao, Yang, Dong and Xia.)

Chemotherapy-induced peripheral neuropathy (CIPN) manifests as mechanical allodynia and hyperalgesia, and is one of the main adverse effects of chemotherapeutic agents. Currently available therapeutic drugs are not sufficiently effective for the management of this adverse effect in the clinic. Therefore, the development of novel therapeutic agents for treating CIPN is necessary. Our previous study suggested the potential of aucubin and pedicularis-lactone (1) as active compounds responsible for the anti-allodynic property of Plantaginis Semen. However, the activity of purified 1 has not been evaluated due to its low content in Plantaginis Semen. In the present study, 1 was isolated from Viticis Fructus, as well as viteoid I (2) and viteoid II (3) during the process of isolation. The purities of isolated 1, 2, and 3 were determined as 67.15%, 92.12%, and 86.72%, respectively, by quantitative 1 H-NMR, using DSS-d 6 as an internal standard. Repeated daily oral administration of these three iridoids at a dose of 15 mg/kg significantly inhibited the PTX-induced mechanical allodynia in mice, suggesting the anti-allodynic activities of 1, 2, and 3. This study provides confirmatory evidence for the anti-allodynic activity of purified 1 and also reveals two additional active iridoids from Viticis Fructus. These three iridoids could be potential candidates for the treatment of CIPN.

The article Search of anti-allodynic compounds from Plantaginis Semen, a crude drug ingredient of Kampo formula "Goshajinkigan".

Currently available methods (e.g., interfacial protection and phase separation) for preparing Janus nanoparticles are often complex and expensive. Furthermore, the preparation of Janus nanoparticles with a particle size below 10 nm is challenging. In this work, we combine an in situ surface-modification route with a chemical etching route to establish a novel "cut the Gordian knot" method for the preparation of functional Janus-SiO 2 nanoparticles. Hydrophobic SiO 2 nanoparticles with a three-dimensional network structure prepared via an in situ surface-modification route were dispersed in NaOH solution containing surfactant or ethanol to enable corrosion close to the modifier-nanoparticle interface with a relatively low content of surface modifiers. Thus, amphipathic Janus-SiO 2 nanoparticles with a hydrophilic surface containing Si-OH species and a hydrophobic surface containing -CH 3 fragments were generated. The as-prepared Janus-SiO 2 nanoparticles with a size of 4-9 nm and a specific surface area of up to 612.9 m 2 /g can be easily dispersed in water, and they also can transfer from the water phase to the oil phase by tuning the surface polarity. Moreover, they can be tuned to achieve bidirectional regulation of surface wettability plus a reduction of the oil/water interface tension. Hence, a significant reduction (by 33∼50%) of water injection pressure and an enhanced oil recovery (EOR) (by 21.1% ∼ 26.6%) can be achieved. Apart from that, Janus-SiO 2 nanoparticles are able to increase the viscosity of partially hydrolyzed polyacrylamide by 282.9% and significantly decrease its viscosity loss ratio in brine, causing an EOR of about 36.6%. With simple, low-cost, and scalable procedures, the following approach could be well applicable to fabricating Janus-SiO 2 nanoparticles with a high potential for augmented water injection as well as EOR of low-permeability reservoirs.

Multifocal structured illumination microscopy (MSIM) is the parallelized version of image scanning microscopy (ISM) that is created by using many excitation spots, which provides a two-fold resolution enhancement beyond the diffraction limit with a frequency of 1 Hz per 3D picture, but scattered and out-of-focus light in thick samples degrades MSIM optical sectioning performance. Herein, we introduce a new optical sectioning method in MSIM via illumination fluctuation. The proposed method suppresses the out-of-focus light by taking full advantage of the statistic property of MSIM raw data and has no requirement of changing the system setup or projecting more illumination patterns. Experimental results demonstrate that the method can reduce the out-of-focus light by 7.25 times in optical sectioning image.

A 10-week feeding trial was conducted to investigate the effects of dietary bile acids (BA) on growth, glucose and lipid metabolism, liver histopathology, and the underlying regulation mechanism on AKT/FOXO1 (forkhead box O1) and cAMP/AMPK/SREBP1 (sterol regulatory element-binding protein 1) pathway in largemouth bass ( Micropterus salmoides ) fed with a high starch diet. Six experimental diets were prepared with BA levels at 0 (B0), 80 (B80), 160 (B160), 240 (B240), 300 (B300), and 600 (B600) mg/kg in a basal diet with 18.7% starch. Each diet was fed to six replicates with 30 fish (6.17 ± 0.03 g) in each tank. The highest weight gain rate (WGR) was observed in B300 group and the optimal level of BA was estimated at 475 mg/kg by a monistic cubic equation regression analysis. Dietary BA inclusion decreased hepatosomatic index (HSI) and hepatic lipid content significantly. The fish in B300 group clearly showed alleviated hepatic fibrosis, but more steatohepatitis symptoms diagnosed with various histopathological and immunofluorescence analysis. 10 out of 12 samples were observed hepatic fibrosis in B0 group while only two fibrosis samples in B300 group. The promoted liver histopathology by dietary BA was related to improved glucose and lipid metabolism. Dietary BA inhibited the expression of G6Pase by activating AKT and reducing FOXO1 transcription, which improved the regulation ability of gluconeogenesis, activated cAMP/AMPK and repressed SREBP1 transcription to inhibit hepatic lipogenesis, which prevented hepatic lipid accumulation. In conclusion, dietary BA enhanced the growth and alleviated liver fibrosis induced by a high starch diet to steatohepatitis/recovery symptom via improving glucose and lipid metabolism, which regulated by AKT/FOXO1 and cAMP/AMPK/SREBP1 pathway in largemouth bass., (Copyright © 2019 Yu, Zhang, Chen, Liang, Cao, Han, Wu, Zheng, Qin and Xue.)

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the dose-limiting side effects of cancer chemotherapy. Although the control of CIPN is important, it is difficult to manage with currently available therapeutic drugs. Therefore, there is a need for novel therapeutic agents for treating CIPN. Goshajinkigan (GJG) is a Kampo formula composed of ten crude drugs. While GJG has been used for the treatment of CIPN, the active constituents of GJG and their underlying mechanisms of pharmacological effects are still unknown. Our previous study revealed that repetitive oral administration of the water extract of Plantaginis Semen, a crude drug ingredient of GJG, inhibited the mechanical allodynia induced by an intraperitoneal injection of paclitaxel in mice. To elucidate the active compounds of Plantaginis Semen, activity-guided separation of the water extract of Plantaginis Semen was performed. From the active fraction, four iridoids (1-4) were identified. Repetitive oral administration of aucubin (1) at 100 or 30 mg/kg and 100 mg/kg of the fraction crude 3 [primarily comprised of pedicularis-lactone (3)], showed anti-allodynic activity, suggesting 1 and 3 could be some of the active compounds responsible for the anti-allodynic property of Plantaginis Semen and GJG. Our study establishes that oral administration of 1 has potent anti-allodynic effect in addition to the activity of intraperitoneally administered 1 reported previously. Identification of active anti-allodynic compounds found in Kampo formulations will support the development of novel therapies for the management of CIPN in cancer patients.

Transcervical resection of adhesion (TCRA) is the standard treatment for the intrauterine adhesions, but the recurrence of adhesions is a tough problem for the gynecologist. In addition, the therapeutic strategy after TCRA about prevention of recurrence remains controversial especially for the patients with moderate to severe intrauterine adhesions (IUAs). Hence, we designed this study to explore the safety and efficacy of fresh amnion grafts for preventing the recurrence after TCRA for patients with moderate to severe IUAs. One hundred patients with moderate to severe IUAs who presented with a history of hypomenorrhea, amenorrhea and infertility were included in the study from January 2015 to December 2017. Patients were divided into amnion group (52 patients) and chitosan group (48 patients). Fresh amnion grafts or intrauterine injections of chitosan were administered after TCRA. Transvaginal ultrasonography (TVUS) and hysteroscopy were performed at the first and third month after the operation. The surgical procedures for all patients were completed successfully without relevant complications. In amnion group, 8 patients exhibited relapse in the first month and 2 patients in three months after surgery; in chitosan group, 23 women exhibited relapse in the first month and 18 patients in three months after surgery. Statistical analysis revealed that the recurrence rate of adhesion in amnion group was significantly lower than those of chitosan group in the first and three months after surgery ( P 1  = 0.000, P 2  = 0.000). After TCRA, fresh amnion graft plays a significant role in preventing further adhesions than injections of chitosan., (© 2020 Chongqing Medical University. Production and hosting by Elsevier B.V.)

Hypoxia serves a critical role in the pathogenesis of liver fibrosis. Hypoxia‑inducible factor 1α (HIF1‑α) is induced when cells are exposed to low O2 concentrations. Recently, it has been suggested that Rho‑associated coiled‑coil‑forming kinase 1 (ROCK1) may be an important HIF1‑α regulator. In the present study, it was analyzed whether crosstalk between HIF1‑α and ROCK1 regulates cell proliferation and collagen synthesis in hepatic stellate cells (HSCs) under hypoxic conditions. For this purpose, a rat hepatic HSC line (HSC‑T6) was cultured under hypoxic or normoxic conditions, and HIF1‑α and ROCK1 expression was measured at different time points. Additionally, HSC‑T6 cells were transfected with HIF1‑α small interfering RNA (siHIF1‑α), and measured protein expression and mRNA transcript levels of α‑smooth muscle actin, collagen 1A1 and ROCK1. Collagen 3A1 secretion was also measured by ELISA. Cell proliferation was assessed by the MTT assay under these hypoxic conditions. The results indicated that a specific ROCK inhibitor, Y‑27632, increased HIF1‑α and ROCK1 expression over time in HSC‑T6 cells in response to hypoxia. In addition, knockdown of HIF1‑α inhibited HSC‑T6 proliferation, suppressed collagen 1A1 expression, decreased collagen 3A1 secretion and attenuated ROCK1 expression. Notably, ROCK1 inhibition caused HSC‑T6 quiescence, suppressed collagen secretion and downregulated HIF1‑α expression. Collectively, these findings indicated that the interplay between HIF1‑α and ROCK1 may be a critical factor that regulates cell proliferation and collagen synthesis in rat HSCs under hypoxia.

One-dimensional (1D) Ce-La nanorods with different La contents (Ce and La in the molar ratio of 1:0, 3:1, 1:1, 1:3, and 0:1) were synthesized by hydrothermal process. Au/Ce-La nanorod catalysts were obtained by a modified deposition-precipitation method. The samples were characterized by N 2 adsorption-desorption (BET), ICP, X-ray diffraction (XRD), SEM, TEM, EDX, X-ray photoelectron spectroscopy (XPS), UV-vis diffuse reflectance spectroscopy (UV-vis DRS), and temperature-programmed reduction (H 2 -TPR). It revealed that La existed as LaO x in the 1D nanorods. The catalysis results demonstrated that the mixed binary Ce-La nanorod oxides could be a good support for gold catalysts. The contents of La had an important influence on the catalytic performance of Au/Ce-La nanorod catalysts. Among the catalysts, when the Ce/La molar ratio was 3:1, the 1.0%Au/Ce 0.75 -La 0.25 nanorods pretreated at 300 °C showed the best activity among the catalysts for CO oxidation, which could convert CO completely at 30 °C. The catalysts also performed high temperature resistance and good stability for CO oxidation at the reaction temperatures of 40, 70, and 200 °C.

Activation of hepatic stellate cells (HSCs) is a pivotal event during hepatic fibrogenesis. Activated HSCs are the main source of collagen and other extracellular matrix (ECM) components, and emerging antifibrotic therapies are aimed at preventing ECM synthesis and deposition. MicroRNAs (miRNAs) have been demonstrated to exert regulatory effects on HSC activation and ECM synthesis. In the present study, the HSC‑T6 rat hepatic stellate cell line was transiently transfected with a miRNA (miR)‑203 mimic, which is an artificial miRNA that enhances the function of miR‑203, with a miR‑203 inhibitor or with a scramble miRNA negative control. mRNA and protein expression levels of collagen (COL) 1A1, COL3A1, α‑smooth muscle actin (α‑SMA) and mothers against decapentaplegic homolog 3 (SMAD3) were assessed using reverse transcription‑quantitative polymerase chain reaction and western blot analysis, respectively. The interaction between miR‑203 and the 3'‑untranslated region (UTR) of SMAD3 mRNA was examined using a dual‑luciferase reporter assay. The proliferative capabilities of activated HSCs were measured using an MTT assay. The present results demonstrated that the mRNA and protein expression levels of COL1A1, COL3A1, α‑SMA and SMAD3 were significantly upregulated following transfection of HSC‑T6 cells with the miR‑203 inhibitor. Conversely, COL1A1, COL3A1, α‑SMA, and SMAD3 mRNA and protein expression appeared to be downregulated in rat HSCs transfected with miR‑203 mimics. Notably, the inhibition of miR‑203 expression was revealed to promote HSC proliferation, whereas increased miR‑203 expression suppressed the proliferative capabilities of HSC‑T6 cells. Furthermore, SMAD3 was revealed to be a direct target of miR‑203. The present study suggested that miR‑203 may function to prevent the synthesis and deposition of ECM components, including COL1A1, COL3A1 and α‑SMA, and to inhibit the proliferation of HSCs through a SMAD3‑dependent mechanism. Therefore, it may be hypothesized that miR‑203 has potential as a novel target for the development of alternative therapeutic strategies for the treatment of patients with hepatic fibrosis in clinical practice.