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Background: Metastasis is the major cause of treatment failure in cancer patients and cancer-associated death, and an antimetastatic drug would be a beneficial therapy for cancer patients. HM-3-HSA is a fusion protein which improved the pharmacokinetics of HM-3 and exerted antitumor and anti-angiogenesis activity in multiple tumor models. However, the efficacy of HM-3-HSA in cancer cell migration and metastasis has not been elucidated. Materials and methods: Herein, high-cell density fermentation of Pichiapink strain expressing HM-3-HSA was performed for the first time. Then, the desired protein was purified by Butyl Sepharose High performance, Capto Blue, Phenyl Sepharose 6FF HS and DEAE Sepharose FF. Furthermore, the effect of HM-3-HSA on the migration and invasion of cancer cells was also evaluated, and B16F10 metastasis model was established to detected the anti- metastasis effect of HM-3-HSA in vivo. Conclusion: The results indicated that the yield of HM-3-HSA was 320 mg/L in a 10 L fermenter, which was a 46% increase over that expressed in flask cultivation. The desired protein was purified by four-step, which yielded a 40% recovery of a product that had over 99% purity. Purified HM-3-HSA significantly suppressed the migration and invasion of HCT-116, SMMC-7721 and B16F10 cell lines. On the other hand, in the B16F10 metastasis model, HM-3-HSA significantly inhibited pulmonary metastases of B16F10 cells, suggesting that HM-3-HSA exerted the anti-metastasis effect in vivo

The effect of free space on molecular motion inside the polymer "dead layer" or adsorbed nanolayers on solid surfaces is investigated. Free space is introduced into the nanolayer by choosing a polymer with a relatively big side group, poly

Optic nerve sheath diameter (ONSD) measurement is one of the non-invasive methods recommended for increased intracranial pressure (ICP) monitoring.This study aimed to evaluate the roles of optic nerve sheath diameter (ONSD) and ONSD/eyeball transverse diameter (ETD) ratio in predicting prognosis of death in comatose patients with acute stroke during their hospitalization.A total of 67 comatose patients with acute stroke were retrospectively recruited. The ONSD and ETD were measured by cranial computed tomography (CT) scan. All patients underwent cranial CT scan within 24 h after coma onset. Patients were divided into death group and survival group according to their survival status at discharge. The differences of the ONSD and ONSD/ETD ratio between the two groups and their prognostic values were compared.The ONSD and ONSD/ETD ratio were 6.07 ± 0.72 mm and 0.27 ± 0.03 in the comatose patients, respectively. The ONSD was significantly greater in the death group than that in the survival group (6.32 ± 0.67 mmThe mortality increased in comatose patients with acute stroke when the ONSD was5.7 mm or the ONSD/ETD ratio was0.25. Both indexes could be used as prognostic tools for comatose patients with acute stroke. The ONSD/ETD ratio was more stable than the ONSD alone, which would be preferred in clinical practice.

The emerging SARS-CoV-2 variants, commonly with many mutations in S1 subunit of spike (S) protein are weakening the efficacy of the current vaccines and antibody therapeutics. This calls for the variant-proof SARS-CoV-2 vaccines targeting the more conserved regions in S protein. Here, we designed a recombinant subunit vaccine, HR121, targeting the conserved HR1 domain in S2 subunit of S protein. HR121 consisting of HR1–linker1–HR2–linker2–HR1, is conformationally and functionally analogous to the HR1 domain present in the fusion intermediate conformation of S2 subunit. Immunization with HR121 in rabbits and rhesus macaques elicited highly potent cross-neutralizing antibodies against SARS-CoV-2 and its variants, particularly Omicron sublineages. Vaccination with HR121 achieved near-full protections against prototype SARS-CoV-2 infection in hACE2 transgenic mice, Syrian golden hamsters and rhesus macaques, and effective protection against Omicron BA.2 infection in Syrian golden hamsters. This study demonstrates that HR121 is a promising candidate of variant-proof SARS-CoV-2 vaccine with a novel conserved target in the S2 subunit for application against current and future SARS-CoV-2 variants.

The deployment of a modular truss antenna reflector is relied on the driven energy of the springs between the components of the structure. The deployment process is characterized by fast speed and large impact. In order to study the impact characteristics of antenna deployment on the boundary, the deployment dynamic analysis of a modular truss antenna reflector is carried out. The deployment impact experiment is performed to obtain the impact forces of the reflector on the boundary. The dynamic model of the modular truss reflector is modified according to the experiment results. The dynamic analysis of a satellite with an arm and a modular truss reflector is conducted by using the modified reflector model. The dynamic behavior of the satellite in orbit during the modular truss antenna reflector deployment is predicted.

The space truss deployable antenna has low natural frequency, multi-closed-loop, and multiredundant structure characteristics, which is a kind of flexible antenna. It is hard to obtain the vibration characteristics under low frequency by finite element analysis or conventional shaking table test. To verify the structure characteristics of the antenna in the folded state below 2 Hz, a low-frequency vibration system is established based on the 6-DOF Stewart platform. Rotation matrix analysis method was adopted to obtain the platform’s velocity and acceleration characteristics. Then, a low-frequency vibration test was carried out on the platform. The results show that the natural frequency of the antenna is 1.51 Hz and the maximum dynamic displacement is 140.6 mm, which provides a certain foundation for the further development of the space truss antenna.

Observational studies have shown abnormal changes in trimethylamine N-oxide (TMAO) levels in the peripheral circulatory system of Parkinson’s disease (PD) patients. TMAO is a gut microbiota metabolite that can cross the blood–brain barrier and is strongly related to neuroinflammation. Neuroinflammation is one of the pathological drivers of PD. Herein, we investigated the effect of TMAO on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model mice. TMAO pretreatment was given by adding 1.5% (w/v) TMAO to the drinking water of the mice for 21 days; then, the mice were administered MPTP (20 mg/kg, i.p.) four times a day to construct an acute PD model. Their serum TMAO concentrations, motor function, dopaminergic network integrity, and neuroinflammation were then assayed. The results showed that TMAO partly aggravated the motor dysfunction of the PD mice. Although TMAO had no effect on the dopaminergic neurons, TH protein content, and striatal DA level in the PD mice, it significantly reduced the striatal 5-HT levels and aggravated the metabolism of DA and 5-HT. Meanwhile, TMAO significantly activated glial cells in the striatum and the hippocampi of the PD mice and promoted the release of inflammatory cytokines in the hippocampus. In summary, higher-circulating TMAO had adverse effects on the motor capacity, striatum neurotransmitters, and striatal and hippocampal neuroinflammation in PD mice.

HIV-1 is a highly host-specific retrovirus that infects humans but not most nonhuman primates. Thus, the lack of a suitable primate model that can be directly infected with HIV-1 hinders HIV-1/AIDS research. In the previous study, we have found that the northern pig-tailed macaques (NPMs) are susceptible to HIV-1 infection but show a nonpathogenic state. In this study, to understand this macaque–HIV-1 interaction, we assembled a de novo genome and longitudinal transcriptome for this species during the course of HIV-1 infection. Using comparative genomic analysis, a positively selected gene, Toll-like receptor 8, was identified with a weak ability to induce an inflammatory response in this macaque. In addition, an interferon-stimulated gene, interferon alpha inducible protein 27, was upregulated in acute HIV-1 infection and acquired an enhanced ability to inhibit HIV-1 replication compared with its human ortholog. These findings coincide with the observation of persistently downregulated immune activation and low viral replication and can partially explain the AIDS-free state in this macaque following HIV-1 infection. This study identified a number of unexplored host genes that may hamper HIV-1 replication and pathogenicity in NPMs and provided new insights into the host defense mechanisms in cross-species infection of HIV-1. This work will facilitate the adoption of NPM as a feasible animal model for HIV-1/AIDS research.

Urotensin II (U-II) and its receptor (UT) are involved in the pathogenesis of various diseases; however, their association with the development of cystitis has not been elucidated. The present study was designed to investigate the functional role of U-II/UT signaling in cyclophosphamide (CYP)-induced cystitis. A total of 60 female rats were randomly divided into the control and CYP-treated groups. Intraperitoneal injection of CYP successfully induced cystitis in rats of the CYP-treated group. The protein and mRNA expression levels of U-II and UT were significantly enhanced in rat bladder tissues of the CYP-treated group. Furthermore, the results of the immunofluorescence staining analysis demonstrated that CYP treatment apparently increased the expression levels of UT in the urothelium layer, detrusor smooth muscle, and bladder interstitial Cajal-like cells. The selective antagonist of UT, SB657510 (10 μm), significantly suppressed the CYP-induced increase in the spontaneous contractions of muscle strips and ameliorated the bladder hyperactivity of CYP-treated rats. Moreover, CYP treatment significantly increased the protein expression levels of Ras homolog family member (Rho) A and Rho-associated protein kinase 2 in rat bladder tissues. Following pretreatment with the Rho-kinase inhibitor Y-27632 (10 μm), the inhibitory effects of SB657510 (10 μm) on the spontaneous contractions of muscle strips were eliminated. In conclusion, the results of the present study suggested that activation of U-II/UT signaling promoted the development of cystitis-associated-bladder hyperactivity by targeting the RhoA/Rho-kinase pathway, indicating that the U-II/UT signaling could serve as a novel target for the treatment of interstitial cystitis/bladder pain syndrome.

Fabrication and processing approaches that facilitate the ease of patterning and the integration of nanomaterials into sensor platforms are of significant utility and interest. In this work, we report the use of laser-induced thermal voxels (LITV) to fabricate microscale, planar gas sensors directly from solutions of metal salts. LITV offers a facile platform to directly integrate nanocrystalline metal oxide and mixed metal oxide materials onto heating platforms, with access to a wide variety of compositions and morphologies including many transition metals and noble metals. The unique patterning and synthesis flexibility of LITV enable the fabrication of chemically and spatially tailorable microscale sensing devices. We investigate the sensing performance of a representative set of n-type and p-type LITV-deposited metal oxides and their mixtures (CuO, NiO, CuO/ZnO, and Fe

Severe fever with thrombocytopenia syndrome virus (SFTSV), an emerging bunyavirus, causes severe fever with thrombocytopenia syndrome (SFTS), with a high fatality rate of 20%–30%. At present, however, the pathogenesis of SFTSV remains largely unclear and no specific therapeutics or vaccines against its infection are currently available. Therefore, animal models that can faithfully recapitulate human disease are important to help understand and treat SFTSV infection. Here, we infected seven Chinese rhesus macaques (Macaca mulatta) with SFTSV. Virological and immunological changes were monitored over 28 days post-infection. Results showed that mild symptoms appeared in the macaques, including slight fever, thrombocytopenia, leukocytopenia, increased aspartate aminotransferase (AST) and creatine kinase (CK) in the blood. Viral replication was persistently detectable in lymphoid tissues and bone marrow even after viremia disappeared. Immunocyte detection showed that the number of T cells (mainly CD8+ T cells), B cells, natural killer (NK) cells, and monocytes decreased during infection. In detail, effector memory CD8+ T cells declined but showed increased activation, while both the number and activation of effector memory CD4+ T cells increased significantly. Furthermore, activated memory B cells decreased, while CD80+/CD86+ B cells and resting memory B cells (CD27+CD21+) increased significantly. Intermediate monocytes (CD14+CD16+) increased, while myeloid dendritic cells (mDCs) rather than plasmacytoid dendritic cells (pDCs) markedly declined during early infection. Cytokines, including interleukin-6 (IL-6), interferon-inducible protein-10 (IP-10), and macrophage inflammatory protein 1 (MCP-1), were substantially elevated in blood and were correlated with activated CD4+ T cells, B cells, CD16+CD56+ NK cells, CD14+CD16+ monocytes during infection. Thus, this study demonstrates that Chinese rhesus macaques infected with SFTSV resemble mild clinical symptoms of human SFTS and provides detailed virological and immunological parameters in macaques for understanding the pathogenesis of SFTSV infection.

Structural stiffness of phononic crystals (PnCs) can affect their bandgap properties. It thus needs to consider stiffness in the design of the unit cell of a PnC. In this paper, a local resonant (LR) rod composed of tri-wing rhombus ligament (TRL) resonators arranged periodically within a common hollow rod is proposed to create a low-frequency flexural vibration bandgap. The dispersion relations, mode of resonances and vibration transfer function are studied using a finite element method. Low-frequency forbidden bands can be effectively shifted by changing the resonator geometries. In addition, both numerical simulations and sample test are conducted to verify the low-frequency bandgap. The results show that the hollow rod with TRL resonators can create a low-frequency flexural vibration bandgap as well as have high support structure stiffness.

Accumulative studies suggest that inflammatory bowel disease (IBD) may cause multiple central nervous system (CNS) pathologies. Studies have found that indoleamine-2,3-dioxygenase (IDO, rate-limiting enzyme of the kynurenine (Kyn) pathway) deficient mice were protected from endotoxin induced cognitive impairment, and Kyn administration induced cognitive memory deficits in both control and IDO-deficient mice. However, there is no investigation of the brain Kyn pathway in IBD, thus we investigated whether dextran sulfate sodium (DSS)-induced colitis could cause dysregulation of Kyn pathway in brain, and also in serum. C57BL/6J mice were given drinking water with 2% DSS for 10 consecutive days to induce colitis. In serum, we found significant increase in Kyn and kynurenic acid (Kyna) level, which was regulated by IDO-1 and KAT2 (rate-limiting enzymes of Trp-Kyn-Kyna pathway). Similarly, by analyzing GEO datasets, higher IDO-1 levels in peripheral blood monocytes and colon of UC patients was found. Furthermore, the Kyn pathway was significantly upregulated in the cerebral cortex under the action of IDO-1 after DSS treatment, which ultimately induced the neurotoxic phenotype of astrocytes. To investigate whether gut microbiota is involved in IBD-induced Kyn pathway dysregulation, we performed intestinal flora 16S rRNA sequencing and found that DSS-induced colitis significantly altered the composition and diversity of the gut microbiota. Metabolic function analysis also showed that Tryptophan metabolism, NOD-like receptor signaling pathway and MAPK signaling pathway were significantly up-regulated in the 2% DSS group. A significant association between intestinal flora and Trp metabolism (both in serum and brain) was found by correlation analysis. Overall, this study revealed that DSS-induced colitis causes dysregulation of the Kyn pathway in serum and brain by affecting rate-limiting enzymes and intestinal flora.

IntroductionSurplus use of chemical nitrogen (N) fertilizers to increase agricultural Q9 production causes severe problems to the agricultural ecosystem and environment. This is contrary to N use efficiency and sustainable agricultural production.MethodsHence, this study was designed to investigate the effect of maizesoybean intercropping on N uptake, N yield, N utilization use efficiency, and the associated nitrogen assimilatory enzymes of maize crops under different N fertilization for two consecutive years 2021-2022.ResultsThe findings of the study showed that intercropping at the optimal N rate (N1) (250 kg N ha-1) increased significantly maize grain yield by 30 and 34%, residue yield by 30 and 37%, and 100-grain weight by 33 and 39% in the year 2021 and 2022, respectively. As compared with mono-cropping, at this optimal N rate, the respective increase (of maize’s crop N yield indices) for 2021 and 2022 were 53 and 64% for grain N yield, and 53 and 68% for residue N yield. Moreover, intercropping at N1 resulted in higher grain N content by 28 and 31%, residue N content by 18 and 22%, and total N uptake by 65 and 75% in 2021 and 2022, respectively. The values for the land equivalent ratio for nitrogen yield (LERN) were greater than 1 in intercropping, indicating better utilization of N under the intercropping over mono-cropping. Similarly, intercropping increased the N assimilatory enzymes of maize crops such as nitrate reductase (NR) activity by 19 and 25%, nitrite reductase (NiR) activity by 20 and 23%, and glutamate synthase activity (GOGAT) by 23 and 27% in 2021 and 2022, respectively. Consequently, such increases resulted in improved nitrogen use efficiency indices such as N use efficiency (NUE), partial factor nitrogen use efficiency (PFNUE), nitrogen uptake efficiency (NUpE), and nitrogen agronomic efficiency (NAE) under intercropping than mono-cropping. ConclusionThus, this suggests that maize-soybean intercropping under optimal N fertilization can improve the nitrogen status and nitrogen use efficiency of maize crops by regulating the nitrogen assimilatory enzymes, thereby enhancing its growth and yield. Therefore, prioritizing intercropping over an intensive mono-cropping system could be a better option for sustainable agricultural production.

Mustard gas, an erosive chemical agent, is primarily used as a chemical weapon, which seriously threatens human life and health. Therefore, detecting mustard gas and its simulant, 2-chloroethyl ethyl sulfide...

Chemical warfare agents (CWAs) are chemical substances intended for use in military operations to kill, injure, or incapacitate an enemy. It is very important to detect toxic CWAs at trace levels on site. Compared with traditional CWA analysis instrument methods, chemiresistive gas sensors present advantages of being small, fast, and inexpensive. Chemiresistive gas sensors are still an important research topic with the development of nanofabrication technology and new kinds of sensing materials, including carbon nanotubes, graphene, and black phosphorus (BP). Chemiresistive gas sensors are divided into three categories according to the type of sensitive materials: carbon- and BP-based materials, conductive polymers, and metal oxide semiconductors. A brief analysis was carried out on fabrication strategies using sensitive materials, including hydrogen bonding strategies, nanostructures, morphology, doping effects, composite materials, and other material application methods, and the sensitive materials and detection effects are summarized in this study. This review aims to provide guidance in the development of chemiresistive sensors for the detection of CWAs.