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Abstract It is a consensus in the international manned space field that factors such as microgravity during the space flight can cause anxiety, depression and other important brain function abnormalities in astronauts. However, the neural mechanism at the molecular level is still unclear. Due to the limitations of research conditions, studies of biological changes in the primate brain have been comparatively few. We took advantage of -6° head-down bed rest (HDBR), one of the most implemented space analogues on the ground, to investigate the effects of simulated weightlessness on non-human primate brain metabolites. The Rhesus Macaque monkeys in the experiment were divided into three groups: the control group, the 42-day simulated weightlessness group with HDBR, and the recovery group, which had 28 days of free activity in the home cage after the HDBR. Liquid chromatography-mass spectrometry (LC-MS) was used to perform metabolomics analysis on specific brain areas of the monkeys under three experimental conditions. Our results show that simulated weightlessness can cause neurotransmitter imbalances, the amino acid and energy metabolism disorders, and hormone disturbances. But these metabolomics changes are reversible after recovery. Our study suggests that long-term brain damage in space flight might be reversible at the metabolic level. This lays a technical foundation for ensuring brain health and enhancing the brain function in future space studies.

Abstract Chemotherapy is currently one of the most effective methods in clinical cancer treatment. However, chemotherapy resistance is an important reason for poor chemotherapy efficacy and prognosis, which has become an urgent problem to be solved in the field of cancer chemotherapy. Therefore, it is very important to deeply study and analyze the mechanism of cancer chemotherapy resistance and its regulatory factors. Long non-coding RNA nuclear paraspeckle assembly transcript 1 (LncRNA NEAT1) has been shown to be closely associated with chemotherapy resistance in cancer. NEAT1 induces cancer cell resistance to chemotherapeutic drugs by regulating cell apoptosis, cell cycle, drug transport and metabolism, DNA damage repair, EMT, autophagy, cancer stem cell characteristics, and metabolic reprogramming. This indicates that NEAT1 may be an important target to overcome chemotherapy resistance and is expected to be a potential biomarker to predict the effect of chemotherapy. This article summarizes the expression characteristics and clinical characteristics of NEAT1 in different cancers, and deeply discusses the regulatory role of NEAT1 in cancer chemotherapy resistance and related molecular mechanisms, aiming to clarify NEAT1 as a new target to overcome cancer chemotherapy resistance and the feasibility of chemotherapy sensitizers, with a view to providing a potential therapeutic direction for overcoming the dilemma of cancer resistance in the future.

This study investigated the effects of dietary glutamine on growth performance, antioxidant capacity, and osmoregulation in euryhaline fish (Oreochromis niloticus) under hyperosmotic stress. Nile tilapia was fed four diets with varying glutamine concentrations (0 %, 0.75 %, 1.5 %, and 3 %) at 0 or 16 ppt for 42 days. The results demonstrated that dietary supplementation of 0.75 % glutamine significantly enhanced the growth performance of Nile tilapia under both 0 ppt and 16 ppt salinity. Hyperosmotic stress significantly reduced the crude protein and crude lipid contents while elevated the ash content of the fish. Under hyperosmotic stress, dietary glutamine supplementation significantly increased the antioxidant and immune capacities, and attenuated apoptosis in the liver of tilapia. The expression of ion transporter genes in the gills and kidneys were both significantly increased by dietary glutamine. Meanwhile, glutamine supplementation significantly reduced the levels of inorganic ions in serum while increased serum osmolality. Hyperosmotic stress significantly activated the glycolysis, gluconeogenesis, and pentose phosphate pathways in the liver of tilapia. However, supplementation of glutamine under hyperosmotic stress would significantly enhance the ability of gluconeogenesis of tilapia in the liver. The results of this research suggested that dietary glutamine might promote the growth performance of fish by enhancing their antioxidant capacity and osmoregulation capacity under chronic hyperosmotic stress. This work investigates the role of glutamine in osmolarity regulation and extends the understanding of its mechanism of action, which could provide a reference for hyperosmotic adaptation in aquatic animals.

BackgroundPrevious structural neuroimaging studies linked cerebellar deficits to temporal lobe epilepsy (TLE). The functions of various cerebellar regions are increasingly being valued, and their changes in TLE patients warrant further in-depth investigation. In this study, we used the Spatially Unbiased Infratentorial (SUIT) toolbox with a new template to evaluate the cerebellar structural abnormalities in patients with TLE, and further explored the relationship between the changes of different cerebellar regions and cognition.MethodsThirty-two patients with TLE were compared with 39 healthy controls (HC) matched according to age, gender, handedness, and education level. All participants underwent a high-resolution T1-weighted MRI scan on a 3.0 Tesla scanner. We used a voxel-based morphometry (VBM) approach utilizing the SUIT toolbox to provide an optimized and fine-grained exploration of cerebellar structural alterations associated with TLE.ResultsCompared with HC, TLE patients showed a significant reduction in the volume of gray matter in the Left lobule VI and white matter in the Right Crus II. In the TLE patient group, we conducted partial correlation analysis between the volumes of different cerebellar regions and cognitive rating scale scores, such as MMSE and MoCA. The volume of the Left lobule VI (GM) exhibited a positive correlation with the MMSE score, but no significant correlation was found with the MoCA score. On the other hand, there was no significant correlation observed between the volume of the Right Crus II (WM) and the two cognitive scale scores mentioned above. Furthermore, it was observed that the MMSE was more effective than the MoCA in identifying epilepsy patients with cognitive impairment.ConclusionThis study supported previous research indicating that temporal lobe epilepsy (TLE) is linked to structural changes in the cerebellum, specifically affecting the volume of both gray and white matter. These findings offer valuable insights into the neurobiology of TLE and hold potential to inform the development of enhanced diagnostic methods and more effective treatment approaches.

ObjectivePatients with temporal lobe epilepsy (TLE) often exhibit neurocognitive disorders; however, we still know very little about the pathogenesis of cognitive impairment in patients with TLE. Therefore, our aim is to detect changes in the structural connectivity networks (SCN) of patients with TLE.MethodsThirty-five patients with TLE were compared with 47 normal controls (NC) matched according to age, gender, handedness, and education level. All subjects underwent thin-slice T1WI scanning of the brain using a 3.0 T MRI. Then, a large-scale structural covariance network was constructed based on the gray matter volume extracted from the structural MRI. Graph theory was then used to determine the topological changes in the structural covariance network of TLE patients.ResultsAlthough small-world networks were retained, the structural covariance network of TLE patients exhibited topological irregularities in regular architecture as evidenced by an increase in the small world properties (p

Abstract Objective To investigate the potential diagnostic and prognostic implications of inflammatory cytokine levels in the cerebrospinal fluid (CSF) of patients with spontaneous intracerebral hemorrhage (SICH) upon their initial hospital admission. Methods Our cohort included 100 patients diagnosed with acute SICH, presenting to the Department of Neurosurgery. Additionally, we recruited 50 individuals without central nervous system (CNS) pathology, treated concurrently at our facility, as controls. CSF samples, collected upon hospital entry, were quantitatively assessed for 10 inflammatory cytokines using the Mesoscale Discovery Platform (MSD, Rockville, MD, USA) electrochemiluminescence technology, followed by validation through enzyme-linked immunosorbent assay (ELISA). Results We observed a marked elevation of IL-6, IL-8, IL-10, and TNF-α in the CSF of the SICH subgroup compared to controls. Higher Glasgow Coma Scale (GCS) scores in SICH patients corresponded with lower CSF concentrations of IL-6, IL-8, IL-10, and TNF-α, indicating an inverse relationship. Notably, CSF inflammatory cytokine levels were consistently higher in SICH patients with hydrocephalus than in those without. Increases in IL-6, IL-8, IL-10, and TNF-α in the CSF were notably more pronounced in the poor prognosis group (Glasgow Outcome Scale, GOS 1–3) compared to those with a favorable prognosis (GOS 4–5). The AUC values for these cytokines in predicting SICH prognosis were 0.750, 0.728, 0.717, and 0.743, respectively. Conclusions Initial CSF levels of IL-6, IL-8, IL-10, and TNF-α upon admission provide significant insights into the severity of neural damage and are robust indicators for prognosis in SICH patients.

Highlights A close correlation was found between the growth status of Aspergillus oryzae and L-malate production. Adaptive evolution enhances growth status and capacity of L-malate production of Aspergillus oryzae. Transcriptomic analysis and morphological characterization reveal the growth mechanism of Aspergillus oryzae.

A two-factor (2 × 3) orthogonal test was conducted to investigate the effects of dietary myo-inositol (MI) on the osmoregulation and carbohydrate metabolism of euryhaline fish tilapia (Oreochromis niloticus) under sustained hypertonic stress (20 practical salinity units [psu]). 6 diets containing either normal carbohydrate (NC, 30%) or high carbohydrate (HC, 45%) levels, with 3 levels (0, 400 and 1,200 mg/kg diet) of MI, respectively, were fed to 540 fish under 20 psu for 8 weeks. Dietary MI supplementation significantly improved growth performance and crude protein content of whole fish, and decreased the content of crude lipid of whole fish (P

IntroductionManagement of coastal wetlands has resulted in extensive conservation of this natural resource; however, changes in carbon storage function are not yet known. There is a direct link between landscape and soil carbon storage. Predicting future changes in the landscape and carbon storage in coastal wetlands is important for developing wetland management policies.MethodHere, remote sensing and physical methods were used to measure and calculate the landscape and surface soil carbon stocks of the Liaohe River Estuary Wetland (LREW). The changes in the landscape and soil carbon stocks under three scenarios: natural development, strict protection, and culture pond transfer, were then predicted using the PLUS model.ResultThe results indicate that the surface soil organic carbon storage was 2107.97×103 t, while soil organic carbon density decreased from land to sea. Anthropogenic activity was found to be the main driver of the current landscape evolution. However, the impact of sea level rise is increasing. By 2030, considerably more storage will be gained under the culture pond transfer scenario than at present.DiscussionOur results reveal that some of the methods of ecological restoration may diminish the carbon storage capacity of coastal wetlands. Making full use of areas with high carbon storage potential may be an effective wetland carbon sink management strategy. Governments should consider more comprehensively for a better carbon pool when developing restoration strategies.

The purpose of this study was to explore the relationship between inositol metabolism and carbohydrate metabolism in Nile tilapia (Oreochromis niloticus) under acute hyperosmotic stress. 50 mg/mL glucose solution and PBS was injected to the fish of experimental group and the control group, respectively. The fish were then transferred to 16 psu brackish water for hyperosmotic stress immediately, and sampled at 0, 1, 3, 6, 12, 24, and 48 h post stress. The hyperosmotic stress significantly increased the osmotic pressure, glucose content of serum, the process of glycolysis and gluconeogenesis in the liver of fish in both groups over time. The expression of genes involved in myo-inositol (MI) synthesis and transport was all induced by hypertonicity in gill, kidney and liver of fish in both groups. The injection of glucose solution significantly decreased MI synthesis in gill, kidney and liver, and relieved the apoptosis of liver under acute hyperosmotic stress. However, glucose injection significantly increased Na+K+-ATPase activity in the gill, as well as serum osmotic pressure, and the decomposition of carbohydrate, indicating that additional glucose promoted osmoregulation ability of fish. The results of this research suggested that during the hyperosmotic stress, the injection of exogenous glucose could not only provide energy that required for osmoregulation, but also participate in the osmoregulation by acting as an osmolyte itself.

BackgroundIncreasing evidence shows that the ubiquitin–proteasome system has a crucial impact on lung adenocarcinoma. However, reliable prognostic signatures based on ubiquitination and immune traits have not yet been established.MethodsBioinformatics was performed to analyze the characteristic of ubiquitination in lung adenocarcinoma. Principal component analysis was employed to identify the difference between lung adenocarcinoma and adjacent tissue. The ubiquitin prognostic risk model was constructed by multivariate Cox regression and least absolute shrinkage and selection operator regression based on the public database The Cancer Genome Atlas, with evaluation of the time-dependent receiver operating characteristic curve. A variety of algorithms was used to analyze the immune traits of model stratification. Meanwhile, the drug response sensitivity for subgroups was predicted by the “pRRophetic” package based on the database of the Cancer Genome Project.ResultsThe expression of ubiquitin genes was different in the tumor and in the adjacent tissue. The ubiquitin model was superior to the clinical indexes, and four validation datasets verified the prognostic effect. Additionally, the stratification of the model reflected distinct immune landscapes and mutation traits. The low-risk group was infiltrating plenty of immune cells and highly expressed major histocompatibility complex and immune genes, which illustrated that these patients could benefit from immune treatment. The high-risk group showed higher mutation and tumor mutation burden. Integrating the tumor mutation burden and the immune score revealed the patient’s discrepancy between survival and drug response. Finally, we discovered that the drug targeting ubiquitin and proteasome would be a beneficial prospective treatment for lung adenocarcinoma.ConclusionThe ubiquitin trait could reflect the prognosis of lung adenocarcinoma, and it might shed light on the development of novel ubiquitin biomarkers and targeted therapy for lung adenocarcinoma.

Hepatocellular carcinoma (HCC) patients are mostly diagnosed at an advanced stage, resulting in systemic therapy and poor prognosis. Therefore, the identification of a novel treatment target for HCC is important. B-cell receptor-associated protein 31 (BAP31) has been identified as a cancer/testis antigen; however, BAP31 function and mechanism of action in HCC remain unclear. In this study, BAP31 was demonstrated to be upregulated in HCC and correlated with the clinical stage. BAP31 overexpression promoted HCC cell proliferation and colony formation in vitro and tumor growth in vivo. RNA-sequence (RNA-seq) analysis demonstrated that serpin family E member 2 (SERPINE2) was downregulated in BAP31-knockdown HCC cells. Coimmunoprecipitation and immunofluorescence assays demonstrated that BAP31 directly binds to SERPINE2. The inhibition of SERPINE2 significantly decreased the BAP31-induced cell proliferation and colony formation of HCC cells and phosphorylation of Erk1/2 and p38. Moreover, multiplex immunohistochemistry staining of the HCC tissue microarray showed positive associations between the expression levels of BAP31, SERPINE2, its downstream gene LRP1, and a tumor proliferation marker, Ki-67. The administration of anti-BAP31 antibody significantly inhibited HCC cell xenograft tumor growth in vivo. Thus, these findings suggest that BAP31 promotes tumor cell proliferation by stabilizing SERPINE2 and can serve as a promising candidate therapeutic target for HCC.

MHC-I antigen processes and presentation trigger host-specific anti-viral cellular responses during infection, in which epitope-recognizing cytotoxic T lymphocytes eliminate infected cells and contribute to viral clearance through a cytolytic killing effect. In this study, Hantaan virus (HTNV) GP-derived 9-mer dominant epitopes were obtained with high affinity to major HLA-I and H-2 superfamilies. Further immunogenicity and conservation analyses selected 11 promising candidates, and molecule docking (MD) was then simulated with the corresponding MHC-I alleles. Two-way hierarchical clustering revealed the interactions between GP peptides and MHC-I haplotypes. Briefly, epitope hotspots sharing good affinity to a wide spectrum of MHC-I molecules highlighted the biomedical practice for vaccination, and haplotype clusters represented the similarities among individuals during T-cell response establishment. Cross-validation proved the patterns observed through both MD simulation and public data integration. Lastly, 148 HTNV variants yielded six types of major amino acid residue replacements involving four in nine hotspots, which minimally influenced the general potential of MHC-I superfamily presentation. Altogether, our work comprehensively evaluates the pan-MHC-I immunoreactivity of HTNV GP through a state-of-the-art workflow in light of comparative immunology, acknowledges present discoveries, and offers guidance for ongoing HTNV vaccine pursuit.

Cervical cancer (CC) is the most common malignant tumor in gynecology, and metastasis is an important cause of patient death. MiRNAs (microRNAs) have been found to play key roles in cervical cancer metastasis, but the effect of miR-362-3p in CC is unclear. This study aimed to investigate the role of miR-362-3p in cervical cancer migration and invasion. We compared the expression levels of miR-362-3p in cervical cancer tissues and adjacent normal cervical tissues. In CC tissues, miR-362-3p expression was significantly down-regulated, which is related to the cancer stage and patient survival. MiR-362-3p can effectively inhibit the migration and invasion of cervical cancer cells. The dual-luciferase reporter assay results showed that BCAP31 (B cell receptor associated protein 31) is a direct target protein of miR-362-3p. The results of the immunohistochemical examination of clinical tissue samples showed that BCAP31 was abnormally highly expressed in cervical cancer, which was positively correlated with the clinical stage. BCAP31 knockdown exerted similar effects as miR-362-3p overexpression. Further GSEA analysis showed that BCAP31 may participate in multiple biological processes, such as protein transport, metabolism, and organelle organization. Our results suggest that miR-362-3p inhibits migration and invasion via directly targeting BCAP31 in cervical cancer, and restoring miR-362-3p levels may be a new treatment strategy for cervical cancer in the future.

This study investigated the effect of dietary myo-inositol (MI) on alleviating the adverse effect of the high carbohydrate diet in Nile tilapia (Oreochromis niloticus). Six diets contained either low carbohydrate (LC 30%) or high carbohydrate (HC 45%) with three levels of MI supplementation (0, 400 and 1200 mg/kg diet) to each level of the carbohydrate diet. After an 8-week trial, the fish fed 400 mg/kg MI under HC levels had the highest weight gain and fatness, but the fish fed 1200 mg/kg MI had the lowest hepatosomatic index, visceral index and crude lipid in the HC group. The diet of 1200 mg/kg MI significantly decreased triglyceride content in the serum and liver compared with those fed the MI supplemented diets regardless of carbohydrate levels. Dietary MI decreased triglyceride accumulation in the liver irrespective of carbohydrate levels. The content of malondialdehyde decreased with increasing dietary MI at both carbohydrate levels. Fish fed 1200 mg/kg MI had the highest glutathione peroxidase, superoxide dismutase, aspartate aminotransferase and glutamic-pyruvic transaminase activities. The HC diet increased the mRNA expression of key genes involved in lipid synthesis (DGAT, SREBP, FAS) in the fish fed the diet without MI supplementation. Dietary MI significantly under expressed fatty acid synthetase in fish fed the HC diets. Moreover, the mRNA expression of genes related to lipid catabolism (CPT, ATGL, PPAR-α) was significantly up-regulated with the increase of dietary MI levels despite dietary carbohydrate levels. The gene expressions of gluconeogenesis, glycolysis and MI biosynthesis were significantly down-regulated, while the expression of the pentose phosphate pathway was up-regulated with the increase of MI levels. This study indicates that HC diets can interrupt normal lipid metabolism and tend to form a fatty liver in fish. Dietary MI supplement can alleviate lipid accumulation in the liver by diverging some glucose metabolism into the pentose phosphate pathway and enhance the antioxidant capacity in O. niloticus.

The outbreak of Zika virus (ZIKV) has posed a great challenge to public health in recent years. To address the urgent need of ZIKV RNA assays, we integrate the microfluidic chip embedded with chitosan-modified silicon dioxide capillaries, smartphone-based detection unit to be a C3-system for the rapid extraction and detection of ZIKV RNA. The C3-system is characterized by: (1) four chitosan-modified silicon dioxide capillaries integrated in the microfluidic chip for target ZIKV RNA enrichment and “in situ PCR” (polymerase chain reaction) amplification; (2) smartphone-based point of care (POC) device consisting of a pneumatic subsystem for controlling the nucleic acid extraction processes in the microfluidic chip, a heating subsystem for sample lysis and PCR amplification, and an optical subsystem for signal acquisition. The entire detection processes including sample lysis, ZIKV RNA enrichment, and reverse-transcription polymerase chain reaction (RT-PCR) is achieved in the microfluidic chip. Moreover, PCR buffers can be directly loaded into the chitosan-modified silicon dioxide capillaries for “in situ PCR”, in which the captured ZIKV RNA is directly used for downstream PCR without any loss. ZIKV RNA extracted by the C3-system can be successfully recovered at very low concentrations of 50 transducing units (TU)/mL from crude human saliva. This means that our method of detecting viremia in patients infected with ZIKV is reliable.

Enzyme biofuel cells (EBFCs) can convert chemical or biochemical energy in fuel into electrical energy, and therefore have received widespread attention. EBFCs have advantages that traditional fuel cells cannot match, such as a wide range of fuel sources, environmental friendliness, and mild reaction conditions. At present, research on EBFCs mainly focuses on two aspects: one is the use of nanomaterials with excellent properties to construct high-performance EBFCs, and the other is self-powered sensors based on EBFCs. This article reviews the applied nanomaterials based on the working principle of EBFCs, analyzes the design ideas of self-powered sensors based on enzyme biofuel cells, and looks forward to their future research directions and application prospects. This article also points out the key properties of nanomaterials in EBFCs, such as electronic conductivity, biocompatibility, and catalytic activity. And the research on EBFCs is classified according to different research goals, such as improving battery efficiency, expanding the fuel range, and achieving self-powered sensors.

A comparative study of the extractive desulfurization (EDS) mechanism by Cu(II) and Zn-based ILs ([C4mim]2[MCl4], M = Cu(II) or Zn) has been performed. It is found that the π–π interaction and C-H⋯π interaction play important roles in EDS for both Cu(II) and Zn-based ILs, which is different from Al, Fe-based ILs. In the gas phase models, the interaction energy between Zn-based ILs and dibenzothiophene (DBT) is stronger than the interaction energy of Cu(II)-based ILs. In order to consider the solvent effect, a generic ionic liquid of solvation model has been implemented, which is few considered in the previous calculations of EDS. It is interesting to find that the gap of interaction energies between Cu(II), Zn-based ILs and DBT are reduced when the solvent effect is considered. In addition, by combined discussion of currently theoretical and experimental evidences for metal-based ILs with different compositions, we firstly propose that the EDS performance should be influenced by the balance of the contribution of cation, metal-based anion, metal chlorides and the viscosity. Keywords: Extractive desulfurization, Metal-based ILs, Mechanism, Density functional theory

Cu-doped boron nitride nanosheets (Cu-BNNS) were first reported as promising adsorbents for the solid-phase extraction and determination of rhodamine B (RhB) dye in a food matrix. Different characterizations, including XRD, FTIR, XPS, SEM, and TEM, were performed to confirm the formation of the adsorbent. Then, the adsorption performance of Cu-BNNS was investigated by adsorption kinetics, isotherms, and thermodynamics. Multiple extraction parameters were optimized by single-factor experiments. Under optimized conditions, the recoveries in the food matrix were in the range of 89.8–95.4%, with the spiked levels of 100 ng/mL and 500 ng/mL, respectively. This novel system was expected to have great potential to detect RhB in a wide variety of real samples.

The development of high-efficiency, recyclable, and inexpensive photocatalysts for water splitting for hydrogen production is of great significance to the application of solar energy. Herein, a series of graphene-decorated polyoxoniobate photocatalysts Nb6/PPy-RGO (Nb6 = K7HNb6O19, RGO = reduced graphene oxide, PPy = polypyrrole), with the bridging effect of polypyrrole were prepared through a simple one-step solvothermal method, which is the first example of polyoxoniobate-graphene-based nanocomposites. The as-fabricated photocatalyst showed a photocatalytic H2 evolution activity without any co-catalyst. The rate of 1038 µmol g−1 in 5 h under optimal condition is almost 43 times higher than that of pure K7HNb6O19·13H2O. The influencing factors for photocatalysts in photocatalytic hydrogen production under simulated sunlight were studied in detail and the feasible mechanism is presented in this paper. These results demonstrate that Nb6O19 acts as the main catalyst and electron donor, RGO provides active sites, and PPy acted as an electronic bridge to extend the lifetime of photo-generated carriers, which are crucial factors for photocatalytic H2 production.

Tensile behavior and plastic deformation mechanisms of Fe-22.8Mn-8.48Al-0.86C low-density steel were studied in this thesis. After solution treatment 1100 °C for 1 h; the steels obtained an excellent combination in mechanical properties; with tensile strength of 757.4 MPa and total elongation of 68%; which were attributed to the existence of annealing twins in austenite. The present steel presented a multiple stage strain hardening behavior which was associated with the changes of such dislocation substructures. With the increase of strain, the gradual transition from tangled dislocations to dense dislocation walls and microbands was found in (the transmission electron microscopy) TEM microstructures. Due to the influence of the evolution of the microstructure during the deformation process, the work hardening behavior of the experimental steel shows three distinct stages.