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ABSTRACT Background Tremor‐dominant (TD) and nontremor‐dominant (NTD) Parkinson's disease (PD) showed different responses to rehabilitation. However, the neural mechanism behind this remains unclear. Methods This cohort study explores changes in motor function, brain activation, and functional connectivity following 2 weeks of rehabilitation in TD‐PD and NTD‐PD patients, respectively. A total of 11 TD‐PD patients, 24 NTD‐PD patients, and 21 age‐matched healthy controls (HCs) were included. At baseline, all participants underwent functional magnetic resonance imaging (fMRI) while performing the foot tapping task. Motor symptoms, gait, balance, and task‐based fMRI were then evaluated in patients before and after rehabilitation. Results Compared to HCs, TD‐PD patients showed increased activity in the left inferior frontal gyrus and the right insula, and NTD‐PD patients showed increased activations in the left postcentral gyrus and decreased within‐cerebellar connectivity at baseline. Rehabilitation improved motor function in PD patients regardless of motor subtype. TD‐PD patients showed increased recruitments of the sensorimotor cortex and the bilateral thalamus after rehabilitation, and NTD‐PD patients showed increased cerebellar activation and within‐cerebellar connectivity that was associated with better motor performance. Conclusions This study demonstrated that rehabilitation‐induced brain functional reorganization varied by motor subtypes in PD, which may have important implications for making individualized rehabilitation programs. Trial Registration ClinicalTrials.gov identifier: ChiCTR1900020771

Objective: Hepatoblastoma (HB) is the most commonly seen pediatric liver malignancy. The preliminary experiment of our research group found that cyclin dependent kinase 1 (CDK1) was upregulated in HB. By in silico analysis, long noncoding RNA (lncRNA) HAND2 antisense RNA 1 (HAND2-AS1) was determined as the research object. Herein, HAND2-AS1 expression in HB and its effect and mechanism on HB were extensively investigated. Methods: CDK1-related lncRNAs were searched using the microarray data from the Gene Expression Omnibus (GEO) database and Gene Expression Profiling Interactive Analysis (GEPIA) online database. qRT-PCR, Western blot, and immunohistochemistry were performed to determine the mRNA expression and protein levels of target genes. MTT, flow cytometry and DAPI staining assays were conducted to measure proliferation activity, cell cycle progression, and apoptosis of HB cells. The interaction between lncRNA and protein was determined by RNA pull-down and FISH assays. Luciferase assay was applied to identify whether HAND2-AS1 stimulates the transcription of CDK1. CDK1 mRNA stability was detected through actinomycin D assay. Aycloheximide assay was used to detect the CDK1 protein stability. Results: HAND2-AS1 was downregulated in HB tissues and cells. HAND2-AS1 overexpression impeded HB cells proliferation activity and cycle progression while inducing cell apoptosis of HB cells, while knockdown of HAND2-AS1 emerged the opposite effect. HAND2-AS1 negatively correlated with CDK1. HAND2-AS1 downregulated CDK1 expression by affecting the transcriptional activity, mRNA and protein stability of CDK1. Furthermore, HAND2-AS1 impeded HB cell proliferation and cycle progression while inducing cell apoptosis by downregulating CDK1. Conclusion: Our research highlights that HAND2-AS1 can exert a tumor-suppressive effect on HB through the negative regulation of CDK1, and the HAND2-AS1/CDK1 is expected to be a diagnostic molecular marker and therapeutic target for HB in clinical practice.

The purpose of this study is to explore the interaction between dietary methionine and taurine levels on growth performance, the profiles of amino acids, protein metabolism, and how taurine spares methionine of Chinese mitten crab (Eriocheir sinensis). The crabs were divided into six groups which were fed six diets formulated with two Tau levels (0 and 0.4%) and three Met levels (0.6%, 0.9% and 1.2%). The results showed that the weight gain rate and specific growth rate were the highest in the crabs fed 0.4% Tau and 0.6% Met. Crabs fed 1.2% Met had the highest survival rate and lowest feed conversion ratio. Furthermore, the hepatopancreas and muscle amino acid content were significantly influenced by the interactive effects of Met and Tau (P < 0.05). Moreover, interactive effects of dietary methionine and taurine were significantly observed in the expressions of amino acid metabolism-related genes (P < 0.05). Additionally, crabs fed 1.2% Met and 0% Tau had the highest activities of cysteine decarboxylase (CSD) and cysteine dioxygenase (CDO). In conclusion, the addition of appropriate amount of taurine to the diet can reduce the requirement of methionine for Chinese mitten crab by regulating the activities of CSD and CDO. At the same time, the addition of methionine and taurine could affect the amino acids metabolism. Therefore, the diet formula of Chinese mitten crab needs to consider the metabolism of sulfur-containing amino acids.

Oxidative stress in muscles is closely related to the occurrence of insulin resistance, muscle weakness and atrophy, age-related sarcopenia, and cancer. Aldehydes, a primary oxidation intermediate of polyunsaturated fatty acids, have been proven to be an important trigger for oxidative stress. However, the potential role of linoleic acid (LA) as a donor for volatile aldehydes to trigger oxidative stress has not been reported. Here, we reported that excessive dietary LA caused muscle redox imbalance and volatile aldehydes containing hexanal, 2-hexenal, and nonanal were the main metabolites leading to oxidative stress. Importantly, we identified 5-lipoxygenase (5-LOX) as a key enzyme mediating LA peroxidation in crustaceans for the first time. The inhibition of 5-LOX significantly suppressed the content of aldehydes produced by excessive LA. Mechanistically, the activation of the cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) pathway facilitated the translocation of 5-LOX from the nucleus to the cytoplasm, where 5-LOX oxidized LA, leading to oxidative stress through the generation of aldehydes. This study suggests that 5-LOX is a potential target to prevent the production of harmful aldehydes.

Abstract Cell‐laden hydrogel fibers/tubules are one of the fundamentals of tissue engineering. They have been proven as a promising method for constructing biomimetic tissues, such as muscle fibers, nerve conduits, tendon and vessels, etc. However, current hydrogel fiber/tubule production methods have limitations in ordered cell arrangements, thus impeding the biomimetic configurations. Acoustic cell patterning is a cell manipulation method that has good biocompatibility, wide tunability, and is contact‐free. However, there are few studies on acoustic cell patterning for fiber production, especially on the radial figure cell arrangements, which mimic many native tissue‐like cell arrangements. Here, an acoustic cell patterning system that can be used to produce hydrogel fibers/tubules with tunable cell patterns is shown. Cells can be pre‐patterned in the liquid hydrogel before being extruded as cross‐linked hydrogel fibers/tubules. The radial patterns can be tuned with different complexities based on the acoustic resonances. Cell viability assays after 72 h confirm good cell viability and proliferation. Considering the biocompatibility and reliability, the present method can be further used for a variety of biomimetic fabrications.

Fritillaria taipaiensis P. Y. Li (F. taipaiensis) is a traditional Chinese herbal medicine that has been used for over two millennia to treat cough and expectoration. However, the increasing cultivation of F. taipaiensis has led to the spread of bulb rot diseases. In this study, pathogens were isolated from rotten F. taipaiensis bulbs. Through molecular identification, pathogenicity testing, morphological assessment, and microscopy, Fusarium solani was identified as the pathogen causing bulb rot in F. taipaiensis. The colonization of F. solani in the bulbs was investigated through microscopic observation. The rapid and accurate detection of this pathogen will contribute to better disease monitoring and control. Loop-mediated isothermal amplification (LAMP) and qPCR methods were established to quickly and specifically identify this pathogen. These results provide valuable insights for further research on the prediction, rapid detection, and effective prevention and control of bulb rot in F. taipaiensis.

Abstract Background Pegylated recombinant human granulocyte colony‐stimulating factor (PEG‐rhG‐CSF) can be used in pediatric patients. This study assessed the safety and efficacy of PEG‐rhG‐CSF as a primary prophylactic drug against neutropenia after chemotherapy in pediatric patients with solid tumors or non‐Hodgkin lymphoma (NHL). Patients and Methods This phase II study (between October 2020 and March 2022) enrolled pediatric patients with solid tumors or NHL treated with high‐intensity chemotherapy and with grade ≥3 myelosuppression for at least 14 days during chemotherapy. Prophylactic PEG‐rhG‐CSF was given at 100 μg/kg body weight (maximum total dosage of 6 mg) once 24–48 h following chemotherapy for two cycles. The primary endpoint was the incidence of PEG‐rhG‐CSF‐related adverse events (AEs). The key secondary endpoints were the rates of grade 3/4 neutropenia and febrile neutropenia (FN). Results This study included 160 pediatric patients with a median age of 6.22 (0.29, 18.00) years. Fifty‐eight patients (36.25%) were diagnosed with sarcoma. AEs potentially related to PEG‐rhG‐CSF included bone pain (n = 32), fatigue (n = 21), pain at the injection site (n = 21), and myalgia (n = 20). The rates of grade 3/4 neutropenia and FN during treatment were 57.28% and 29.45%, respectively. Conclusion PEG‐rhG‐CSF is well tolerated and effective in pediatric patients with solid tumors or NHL. These findings should be substantiated with further trials. Clinical Trial Registration ClinicalTrials.gov identifier: NCT04547829.

Abstract Background ASXL1 mutation is an independent prognostic factor in adult acute myeloid leukemia (AML), but its effect on the prognosis of pediatric AML is poorly understood. Aims This study aimed to investigate the clinical characteristics and prognostic factors of ASXL1‐mutant pediatric AML from a large Chinese multicenter cohort. Methods A total of 584 pediatric patients with newly diagnosed AML from 10 centers in South China were enrolled. The exon 13 of ASXL1 was amplified by polymerase chain reaction (PCR), and then analyzed the mutation status of the locus. (n = 59 for ASXL1‐mut group, n = 487 for ASXL1‐wt group). Results ASXL1 mutations were found in 10.81% of all patients with AML. A complex karyotype was significantly less common in the ASXL1‐mut AML group than in the ASXL1‐wt group (1.7% vs. 11.9%, p = 0.013). Furthermore, TET2 or TP53 mutations were predominantly found in the ASXL1+ group (p = 0.003 and 0.023, respectively). The 5‐year overall survival (OS) and event‐free survival (EFS) of the total cohort were 76.9% and 69.9%. In ASXL1‐mut AML patients, a white blood cell (WBC) count ≥50 × 109/L had significantly poorer 5‐year OS and EFS than a WBC count

The groundwater environment in low-lying coastal regions is significantly impacted by global sea-level fluctuation. In Laizhou Bay, three large-scale transgressions have occurred since the late Pleistocene, resulting in the transformation of ancient seawater into brine. This brine has become a major contributor to groundwater salinity in the area. This study establishes a correlation between groundwater occurrence and paleoclimate changes in Laizhou Bay using borehole sediment data. The source and mechanism of groundwater salinity are analyzed based on sediment pore water characteristics and hydrogen and oxygen isotopes. The study reveals that the stratigraphic structures in the area consist of four layers: a Holocene transgressive layer, a continental confining bed from the late Pleistocene, a Cangzhou transgressive layer from the late Pleistocene, and a fluvial aquifer from the middle Pleistocene. All aquifers in the study area have been infiltrated by modern seawater, with the uppermost Holocene aquifer influenced by evaporation and leaching processes, the central late Pleistocene aquifer remaining relatively stable, and the lower middle Pleistocene aquifer affected by subsurface low salinity runoff and exhibiting an increasing trend with depth. Given the presence of numerous hydrogeological environments globally that are similar to the study area, the obtained mechanisms of groundwater salinization in this study will provide theoretical support for groundwater management in similar regions worldwide.

Chinese herbs and their purified components in aquafeeds have been proved effective to combat stress in aquatic animals to combat toxic environmental stress. Lycium barbarum poly-saccharides (LBP) is an active antioxidant, anti-inflammatory and antitoxic purified herbal agent. The objective of this paper was to evaluate the effect of 0.1–2.0% LBP on the hepatopancreas of Chinese mitten crab (Eriocheir sinensis) challenged with 2 mg/kg T-2 toxin orally for 5 weeks. The results showed that feeding LBP significantly restored the hepatopancreas index (HI), gonadsomatic index (GSI) reduced by T-2 toxin. Moreover, H&E sections indicated that LBP dose-dependently restored the disrupted microstructure of the hepatopancreas. In antioxidative capacity, significant increases in malondialdehyde (MDA) reduction and elevated glutathione (GSH) content, gluta-thione reductase (GPx) activity were seen in the 0.5% LBP group. In addition, reactive oxygen species (ROS) and apoptosis rate of hepatopancreas showed the anti-apoptotic effect of LBP doses, plus qPCR assay of 10 apoptosis-related genes to support them. The mRNA abundance of three pro-inflammatory genes was significantly reduced by LBP, corroborating its anti-inflammatory efficacy. In brief, feed supplementation with LBP alleviated the oxidative stress-apoptosis-inflammation induced by co-feeding T-2 toxin in E. sinensis, maintained the structural and functional integrity of the hepatopancreas, prevented degenerative atrophy.

IntroductionBig graphs like social network user interactions and customer rating matrices require significant computing resources to maintain. Data owners are now using public cloud resources for storage and computing elasticity. However, existing solutions do not fully address the privacy and ownership protection needs of the key involved parties: data contributors and the data owner who collects data from contributors.MethodsWe propose a Trusted Execution Environment (TEE) based solution: TEE-Graph for graph spectral analysis of outsourced graphs in the cloud. TEEs are new CPU features that can enable much more efficient confidential computing solutions than traditional software-based cryptographic ones. Our approach has several unique contributions compared to existing confidential graph analysis approaches. (1) It utilizes the unique TEE properties to ensure contributors' new privacy needs, e.g., the right of revocation for shared data. (2) It implements efficient access-pattern protection with a differentially private data encoding method. And (3) it implements TEE-based special analysis algorithms: the Lanczos method and the Nystrom method for efficiently handling big graphs and protecting confidentiality from compromised cloud providers.ResultsThe TEE-Graph approach is much more efficient than software crypto approaches and also immune to access-pattern-based attacks. Compared with the best-known software crypto approach for graph spectral analysis, PrivateGraph, we have seen that TEE-Graph has 103−105 times lower computation, storage, and communication costs. Furthermore, the proposed access-pattern protection method incurs only about 10%-25% of the overall computation cost.DiscussionOur experimentation showed that TEE-Graph performs significantly better and has lower costs than typical software approaches. It also addresses the unique ownership and access-pattern issues that other TEE-related graph analytics approaches have not sufficiently studied. The proposed approach can be extended to other graph analytics problems with strong ownership and access-pattern protection.

Objective: On the basis of national standard GB 4789.35-2016, a comparative study was conducted on dilution ratio, diluent components and medium components to investigate the influence on the number of viable bacteria when counting lactic acid bacteria powder. Nine strains of Lactobacillus, six strains of Bifidobacterium, three strains of coccus and one strain of Bacillus coagulans were used as research objects. Methods: The method of dilution plate count was used to count the viable bacteria of different lactic acid bacteria powders. Results: According to research findings, the dilution ratio of the initial lactic acid bacteria powder sample had no significant effect on the final count of viable bacteria, and the ISO dilution had significant effects on the viable count results of some Lactobacillus and Bifidobacterium powders (P

Rationale and objectives: Fuzi, the dried root of Aconitum carmichaelii Debx, is one of the widely used traditional Chinese medicines. Fuzi polysaccharides are considered the most bioactive compounds with immunomodulatory functions, however, the mechanisms have not been evaluated. This study aims to systematically investigate the effects of Fuzi polysaccharides on the gut microbiota and immune function using a mouse model immunosuppressed with cyclophosphamide. Methods: The short-chain fatty acid levels in cecal contents were measured by gas chromatography-mass spectrometry. The gut microbiota 16S rRNA gene were sequenced by next generation sequencing. The mRNA expression levels of NF-κB, IL-6, TNF-α, iNOS and COX-2 were measured using quantitative real-time polymerase chain reaction. The protein expression of occludin and zonula occludens-1 were analyzed by Western blot. The white blood cells were counted using automated hematology analyzer, and CD4+FOXP3+/CD4+ ratio was measured by flow cytometry. Results and Conclusions: Fuzi polysaccharides had the function of elevating the concentration of acetic acid, propionic acid, isobutyric acid, and n-butyric acid in the cecum. Meanwhile, Fuzi polysaccharides could decrease the relative abundance of Helicobacter, Anaerotruncus, Faecalibacterium, Lachnospira, Erysipelotrichaceae_UCG-003, Mucispirillum, and Mycoplasma, and increase the relative abundance of Rhodospirillales, Ruminococcaceae_UCG-013, Mollicutes_RF39, Ruminococcus_1, Christensenellaceae_R-7_group, and Muribaculaceae in the gut. Furthermore, Fuzi polysaccharides exhibited the function of increasing spleen and thymus indices and number of white blood cells and lymphocytes. Fuzi polysaccharides could reverse the decreased mRNA expression of NF-кB, IL-6, and iNOS, differentiation of CD4+FOXP3+ regulatory T cells as well as protein expression of occludin and zonula occludens-1 induced by cyclophosphamide. In addition, the mRNA and protein expression of cytokines were significantly correlated with the abundance of gut microbiota under Fuzi polysaccharides treatment. Collectively, the above results demonstrated that Fuzi polysaccharides could regulate inflammatory cytokines and gut microbiota composition of immunosuppressive mice to improve immunity, thereby shedding light on revealing the molecular mechanism of polysaccharides of traditional Chinese medicines in the future.

Traditional asphalt pavement is prone to rutting, looseness, and other issues during usage resulting in overall poor durability. The service life of asphalt pavement may be improved, however, by targeted modifications. The modification mechanism and strengthening effect of polyester fiber and straw fiber on asphalt were investigated in this study in an effort to optimize the anti-aging and anti-fatigue performance of asphalt pavement. Molecular dynamics simulation, basic performance testing, dynamic shear rheological testing, and bending beam rheological testing were conducted on fiber-modified asphalt to observe the interaction modes between the asphalt components and its applicable conditions. Fiber appears to have some compatibility with asphalt, which can improve its performance; straw fiber’s ability to modify asphalt at high temperatures is less effective than that of polyester fiber, but it is stronger at low temperatures. Under high-temperature conditions, the optimal dosages of polyester fiber and straw fiber are 3.00 % and 3.00 %, respectively, while at low temperatures, they are 2.00 % and 3.00 %.

IntroductionPrevious observational studies have demonstrated the relationship between leisure sedentary behavior, physical activity, and nonalcoholic liver disease (NAFLD). However, whether these associations are causal or confounding factors remains unclear.MethodsPooled genetic data from the UK Biobank and other large genome-wide association studies (GWAS) were used to extract instrumental variables representing sedentary television watching, computer use, driving, vigorous physical activity (VPA), and moderate-to-vigorous physical activity (MVPA). The two-sample Mendelian randomization (MR) method was used to explain the causal relationship between them and NAFLD. The inverse variance of the weighted method was used as the main analysis method, and MR-Egger, weighted median, MR-PRESSO, and other supplementary methods were also used. A sensitivity analysis was also performed. Simultaneously, the common risk factors for NAFLD were further analyzed for potential mediating associations.ResultsWe observed that sedentary television viewing (odds ratio (OR): 1.84; 95% confidence interval (CI): 1.09–3.10; p = 0.021) and genetically predicted VPA duration (OR: 0.0033; 95% CI: 0.000015–0.70; p = 0.036) were suggestively associated with the risk of NAFLD. Using a computer (OR: 1.51; 95% CI: 0.47–4.81; p = 0.484), driving (OR: 0.78; 95% CI: 0.05–11.94; p = 0.858), and MVPA time (OR: 0.168; 95% CI: 0.01–2.81; p = 0.214) were not significantly associated with NAFLD. The role of heterogeneity versus pleiotropy was limited in all the analyses.DiscussionThis study supports the association between sedentary television watching and an increased risk of NAFLD, along with vigorous physical activity as a possible protective factor for NAFLD.

Abstract Background As one of the imaging markers of cerebral small vessel disease, lacunes has received little attention. The objective of this study was to investigate the associations of lacunes, cognition and motor function in patients with Parkinson's disease (PD) and whether these associations are independent of other imaging markers. Methods Patients were consecutively included from April 2019 to July 2022 in Beijing Rehabilitation Hospital. All patients underwent brain magnetic resonance imaging scans, clinical scale evaluations, and neuropsychological tests, as well as quantitative evaluation of postural control. To eliminate the possible factors contributing to cognition and motor dysfunction in patients with PD, in particular white matter hyperintensities and enlarged perivascular space in the basal ganglia, multivariate linear regression models were constructed to sort out the effect of lacunes. Results Ninety‐four patients were included in this study, 56 without lacunes and 38 with lacunes. Patients with lacunes showed shorter disease duration, slower gait speed and spent more time on Trail‐Making Test part A (TMT‐A) than those without lacunes. The number of lacunes were positively correlated with the time to complete the TMT‐A and negatively related to gait speed. Multivariate linear regression models showed that the presence of lacunes was associated with longer TMT‐A time after adjusting for potential confounders. Conclusions Lacunes were independently associated with worse visual scanning, attention, and processing speed in patients with PD. In addition, lacunes may accelerate the course of PD. Early treatment of vascular disease provides an alternate way to mitigate some motor and cognitive dysfunction in patients with PD.

Long-term feed route exposure to T-2 toxin was proved to elicit growth retarding effects and induction of oxidative stress and apoptosis in Chinese mitten crab (Eriocheir sinensis). However, no study with a holistic perspective has been conducted to date to further describe the in-depth toxicological mechanism of T-2 toxin in E.sinensis. In this study, an RNA-Sequencing (RNA-seq) was used in this study to investigate the effects of feed supplementation with 0 mg/kg and 4 mg/kg T-2 toxin on the hepatopancreas transcriptome of E.sinensis and establish a hepatopancreas transcriptome library of T-2 toxin chronically exposed crabs after five weeks, where 14 differentially expressed genes (DEGs) were screened out across antioxidant, apoptosis, autophagy, glucolipid metabolism and protein synthesis. The actual expression of all the DEGs (Caspase, ATG4, PERK, ACSL, CAT, BIRC2, HADHA, HADHB, ACOX, PFK, eEFe1, eIF4ɑ, RPL13Ae) was also analyzed by real-time quantitative PCR (RT-qPCR). It was demonstrated that long-term intake of large amounts of T-2 toxin could impair antioxidant enzyme activity, promote apoptosis and protective autophagy, disrupt lipid metabolism and inhibit protein synthesis in the hepatopancreas of E.sinensis. In conclusion, this study explored the toxicity mechanism of T-2 toxin on the hepatopancreas of E.sinensis at the mRNA level, which lays the foundation for further investigation of the molecular toxicity mechanism of T-2 toxin in aquatic crustaceans.

Bioprinting of cell-laden hydrogel constructs providing three-dimensional (3D) spatial pattern capacity and suitable cellular microenvironment have become essential tools in the field of tissue engineering. For heterogeneous tissue development, the printing approaches permitting controllable deposition of multicellular components in a flexible manner are urgently needed. Here, a facile dot-extrusion printing (DEP) system for one-step generation of cell-laden gelatin methacrylate (GelMa) hydrogel beads (GHBs) is developed, which allows size-tunable GHBs programmable positioned into complex 3D constructs. The GelMa is in situ semi-gelled at the printhead, thus enabling one-step generation of GHBs onto the platform, as a result of improved printing simplicity, fidelity and flexibility. The size and spatial position of the GHBs are adjustable by programming G-code parameters. Further, by integrating multiple printheads, GHBs encapsulating different cellular components can be printed to fabricate heterogeneous tissue constructs, and maintain the post-printed cell viability over 95%. As an example of application, two different tumor-stroma spatial phases were developed through spatial regionally printing tumor cells and normal fibroblasts into juxtapositional or overlapping microcapsule structures, giving an access to study the complex tumor-stroma interactions in different microenvironments. The developed DEP system thus holds promise for creation of complex and heterogeneous tissues toward various biology studies.

Rehabilitation has been proposed as a valid measure complementary to the management of Parkinson's disease (PD). However, the mechanism underlying is not clear yet. The differential expressions of exosomal messenger RNA (mRNA) and long noncoding RNAs (lncRNAs) may play a critical role in PD progression and rehabilitation. To compare the differential expressions of exosomal mRNAs and lncRNAs, patients with PD (PWPs, Hoehn and Yahr stages 1.5-2.5, n = 6) and age- and sex-matched healthy controls (HCs, n = 6) were included in this study. All PWPs received a 2-week rehabilitation treatment in the hospital, which seemingly led to improvement in both the motor and non-motor functions. A set of differentially expressed mRNAs (DEmRNAs) and differentially expressed lncRNAs (DElncRNAs) extracted from exosomes in blood samples via next-generation sequencing (NGS) was screened out. Compared to HCs, 2,337 vs. 701 mRNAs and 1,278 vs. 445 lncRNAs were significantly upregulated and significantly downregulated, respectively, in pre-rehabilitation (pre-rehab) PWPs; 2,490 vs. 629 mRNAs and 1,561 vs. 370 lncRNAs were significantly upregulated and significantly downregulated, respectively, in post-rehabilitation (post-rehab) PWPs. Compared to pre-rehab PWPs, 606 vs. 1,056 mRNAs and 593 vs. 1,136 lncRNAs were significantly upregulated and significantly downregulated, respectively, in post-rehab PWPs. Overall, 14 differentially expressed mRNAs (DEmRNAs) and 73 differentially expressed lncRNAs (DElncRNAs) were expressed in the blood exosomes of HCs, pre- and post-rehab PWPs, simultaneously. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses identified 243 significantly co-expressed lncRNA-mRNA pairs. One DEmRNA of interest (ENSG00000099795, NDUFB7) and three corresponding DElncRNAs (ENST00000564683, ENST00000570408, and ENST00000628340) were positively related. Quantitative real-time polymerase chain reaction (qRT-PCR) validated that the expression levels of NDUFB7 mRNA and the 3 DElncRNAs increased significantly in pre-rehab PWPs, but decreased significantly in post-rehab PWPs compared to HCs. NDUFB7 mRNA is a marker related to mitochondrial respiration. It is reasonably believed that mitochondrial function is associated with PD rehabilitation, and the mitochondrial pathway may involve in the pathogenesis of PD.

Abstract Lung cancer patients with malignant pleural effusions (MPE) have a particular poor prognosis. It is crucial to distinguish MPE from benign pleural effusion (BPE). The present study aims to develop a rapid, convenient and economical diagnostic method based on FTIR near-infrared spectroscopy (NIRS) combined with machine learning strategy for clinical pleural effusion classification. NIRS spectra were recorded for 47 MPE samples and 35 BPE samples. The sample data were randomly divided into train set (n = 62) and test set (n = 20). Partial least squares, random forest, support vector machine (SVM), and gradient boosting machine models were trained, and subsequent predictive performance were predicted on the test set. Besides the whole spectra used in modeling, selected features using SVM recursive feature elimination algorithm were also investigated in modeling. Among those models, NIRS combined with SVM showed the best predictive performance (accuracy: 1.0, kappa: 1.0, and AUCROC: 1.0). SVM with the top 50 feature wavenumbers also displayed a high predictive performance (accuracy: 0.95, kappa: 0.89, AUCROC: 0.99). Our study revealed that the combination of NIRS and machine learning is an innovative, rapid, and convenient method for clinical pleural effusion classification, and worth further evaluation.

3D cell culture models replicating the complexity of cell–cell interactions and biomimetic extracellular matrix (ECM) are novel approaches for studying liver cancer, including in vitro drug screening or disease mechanism investigation. Although there have been advancements in the production of 3D liver cancer models to serve as drug screening platforms, recreating the structural architecture and tumor-scale microenvironment of native liver tumors remains a challenge. Here, using the dot extrusion printing (DEP) technology reported in our previous work, we fabricated an endothelialized liver lobule-like construct by printing hepatocyte-laden methacryloyl gelatin (GelMA) hydrogel microbeads and HUVEC-laden gelatin microbeads. DEP technology enables hydrogel microbeads to be produced with precise positioning and adjustable scale, facilitating the construction of liver lobule-like structures. The vascular network was achieved by sacrificing the gelatin microbeads at 37 °C to allow HUVEC proliferation on the surface of the hepatocyte layer. Finally, we used the endothelialized liver lobule-like constructs for anti-cancer drug (Sorafenib) screening, and stronger drug resistance results were obtained when compared to either mono-cultured constructs or hepatocyte spheroids alone. The 3D liver cancer models presented here successfully recreate liver lobule-like morphology, and may have the potential to serve as a liver tumor-scale drug screening platform.

Abstract Background Rehabilitation has been reported to improve the quality of life (QoL) of patients with Parkinson's disease (PD). Nevertheless, not all patients are satisfied with rehabilitation outcomes and could achieve a significant improvement in QoL. Objective To detect possible predictors of QoL improvement in patients with PD after rehabilitation. Methods A total of 86 PD patients were included and followed up for 3 months with a 39‐item Parkinson's Disease Questionnaire summary index (PDQ‐39 SI) as the primary endpoint. All patients received 2 weeks of multidisciplinary intensive rehabilitation treatment (MIRT). Changes in patients' QoL were assessed using the PDQ‐39 at baseline and at the 3‐month follow‐up. The reliable change index (RCI) was adapted to determine the individual QoL outcome. The predictors of QoL outcome were detected using logistic regression analysis. Results After a 3‐month follow‐up, PDQ‐39 SI decreased significantly from 22.95 ± 9.75 to 18.73 ± 10.32 (P 10.9) after rehabilitation for 18.6% of the patients, and 74.4% of patients reported an unchanged QoL (−10.9≤RCI≤10.9), while 7.0% of patients reported a worsening of QoL (RCI

Activated phosphoinositide 3-kinase δ syndrome (APDS) is an autosomal dominant primary immunodeficiency caused by acquired gene function mutation (GOF). APDS has a variety of clinical phenotypes, particularly recurrent respiratory infections and lymphoproliferation. Here we report a pediatric patient with APDS who presented with recurrent respiratory infections, lymphoproliferation, hepatosplenomegaly, bronchoscopy suggesting numerous nodular protrusions in the airways and a decrease in both T and B lymphocytes, and progression to plasmablastic lymphoma (PBL) after 1 year. Whole exome sequencing revealed a heterozygous mutation in the PIK3CD gene (c.3061 G>A p.E1021K). This is the first reported case of APDS combined with PBL and pediatricians should follow up patients with APDS regularly to be alert for secondary tumours.

This study investigated the management and clinical outcomes along with associated factors of posterior reversible encephalopathy syndrome (PRES) in childhood hematologic/oncologic diseases. We present data from children with hematologic/oncologic diseases who developed PRES after treatment of the primary disease with chemotherapy and hematopoietic stem cell transplantation (HSCT) at 3 medical centers in Changsha, China from 2015 to 2020, and review all previously reported cases with the aim of determining whether this neurologic manifestation affects the disease prognosis. In the clinical cohort of 58 PRES patients, hypertension [pooled odds ratio (OR) = 4.941, 95% confidence interval (CI): 1.390, 17.570; P = 0.001] and blood transfusion (OR = 14.259, 95% CI: 3.273, 62.131; P = 0.001) were significantly associated with PRES. Elevated platelet (OR = 0.988, 95% CI: 0.982, 0.995; P < 0.001), hemoglobin (OR = 0.924, 95% CI: 0.890, 0.995; P < 0.001), and blood sodium (OR = 0.905, 95% CI: 0.860, 0.953; P < 0.001), potassium (OR = 0.599, 95% CI: 0.360, 0.995; P = 0.048), and magnesium (OR = 0.093, 95% CI: 0.016, 0.539; P = 0.008) were protective factors against PRES. Data for 440 pediatric PRES patients with hematologic/oncologic diseases in 21 articles retrieved from PubMed, Web of Science, and Embase databases and the 20 PRES patients from our study were analyzed. The median age at presentation was 7.9 years. The most common primary diagnosis was leukemia (62.3%), followed by solid tumor (7.7%) and lymphoma (7.5%). Most patients (65.0%) received chemotherapy, including non-induction (55.2%) and induction (44.8%) regimens; and 86.5% used corticosteroids before the onset of PRES. Although 21.0% of patients died during follow-up, in most cases (93.2%) this was not attributable to PRES but to severe infection (27.3%), underlying disease (26.1%), graft-vs.-host disease (14.8%), multiple organ dysfunction syndrome (8.0%), and respiratory failure (3.4%). PRES was more common with HSCT compared to chemotherapy and had a nearly 2 times higher mortality rate in patients with oncologic/hematologic diseases than in those with other types of disease. Monitoring neurologic signs and symptoms in the former group is therefore critical for ensuring good clinical outcomes following treatment of the primary malignancy.

The mitogenome of Parnassius mercurius Grum-Grshimailo is determined to be 15,372 bp in length, including 37 typical insect mitochondrial genes and an AT-rich region. All PCGs start with ATN, except for COI with CGA; 12 of 13 PCGs harbour the common stop codon TAA or TAG, whereas COII end with a single T. The lrRNA and srRNA genes are 1344 bp and 775 bp in length, respectively. The AT-rich region contains several features characteristic of the lepidopterans. Phylogenetic analysis shows that P. mercurius is the closest relative of P. epaphus and P. nomion lineage, rather than the P. jacquemontii.

We describe the mitogenome sequence of alpine butterfly Aglais ladakensis (Lepidoptera: Nymphalidae: Nymphalinae) collected from the Qilianshan Mountain, Gansu province, China. The molecule is 15,222 bp in length, containing 37 typical insect mitochondrial genes and one AT-rich region. All protein-coding genes (PCGs) start with ATN codons, except for COI gene with CGA, which is often found in other butterflies. In addition, seven PCGs harbor the typical stop codon TAA, whereas six PCGs terminate with TA or T. The rrnL and rrnS genes are 1316 bp and 735 bp in length, respectively. The AT-rich region is 394 bp in size and harbors several features characteristic of the lepidopterans, including the motif ATAGA followed by a 19 bp poly-T stretch and a microsatellite-like (TA)8 element. Phylogenetic analysis shows that the Qinghai-Tibet Plateau (QTP) distributed A. ladakensis of this study is closely related to the A. milberti, which is the only Aglais species that occurs in the alpine caves of North America.

Background: Esophageal squamous cell carcinoma (ESCC) is a gastrointestinal malignancy with a poor prognosis. Although studies have shown metabolic reprogramming to be linked to ESCC development, no prognostic metabolic biomarkers or potential therapeutic metabolic targets have been identified.Method: The present study investigated some circulating metabolites associated with overall survival in 276 curatively resected ESCC patients using liquid chromatography/mass spectrometry metabolomics and Kaplan-Meier analysis. Tissue metabolomic analysis of 23-paired ESCC tissue samples was performed to discover metabolic dysregulation in ESCC cancerous tissue. A method consisting of support vector machine recursive feature elimination and LIMMA differential expression analysis was utilized to select promising feature genes within transcriptomic data from 179-paired ESCC tissue samples. Joint pathway analysis with genes and metabolites identified relevant metabolic pathways and targets for ESCC.Results: Four metabolites, kynurenine, 1-myristoyl-glycero-3-phosphocholine (LPC(14:0)sn-1), 2-piperidinone, and hippuric acid, were identified as prognostic factors in the preoperative plasma from ESCC patients. A risk score consisting of kynurenine and LPC(14:0)sn-1 significantly improved the prognostic performance of the tumor-node-metastasis staging system and was able to stratify risk for ESCC. Combined tissue metabolomic analysis and support vector machine recursive feature elimination gene selection revealed dysregulated kynurenine pathway as an important metabolic feature of ESCC, including accumulation of tryptophan, formylkynurenine, and kynurenine, as well as up-regulated indoleamine 2,3-dioxygenase 1 in ESCC cancerous tissue.Conclusions: This work identified for the first time four potential prognostic circulating metabolites. In addition, kynurenine pathway metabolism was shown to be up-regulated tryptophan-kynurenine metabolism in ESCC. Results not only provide a metabolite-based risk score system for prognosis, but also improve the understanding of the molecular basis of ESCC onset and progression, and as well as novel potential therapeutic targets for ESCC.

Soyasaponin Ab (SA) is a typical oleanane triterpene saponin isolated from soybean and represents effects of antioxidation and anti-inflammation. In this study, we found the expressions of some phase II detoxifying enzymes were stimulated by SA via the signaling pathway of nuclear factor erythroid 2-related factor 2 (Nrf2) in HepG2 cells. Luciferase assay results demonstrated that SA promoted the Nrf2 transcription via binding to the antioxidant response element. In addition, a combining of luciferase assay and Western blotting suggested that SA activated ERK1/2 signaling pathways, and made Nrf2 translocated from cytoplasm to nucleus. SA also upregulated some Nrf2-related antioxidant enzymes such as heme oxygenase-1 (HO-1), NAD(P)H quinone oxidoreductase-1 (NQO1), and glutamate cysteine ligase catalytic subunit (GCLC). Inhibition of si-Nrf2 resisted expressions of SA-induced antioxidant genes. Collectively, these results suggest that SA exerted its protection against oxidative stress via the Nrf2/HO-1/NQO1 signaling pathways.

Somatic hypermutation of antibodies can occur in infants but are difficult to track. Here the authors present a new method called MIDCIRS for deep quantitative repertoire sequencing with few cells, and show infants as young as 3 months can expand antibody lineage complexity in response to malaria infection.

Background: Ischemic stroke is significantly affected by the dysfunction of the miRNA network. Recent research has described that disordered expression of miR-130a is associated with ischemic stroke. Here, we aimed to investigate the possible mechanism of the miR-130a-mediated neuroprotection that follows ischemia-reperfusion (I/R) injury. Method: This study was comprised of two models: oxygen-glucose deprivation/Reperfusion (OGDR) and middle cerebral artery occlusion (MCAO). RT-PCR and immunoblotting were used to examine gene expression levels, and MTT assay and flow cytometric analysis were used to examine cell states. We also used 2, 3, 5-triphenyltetrazolium chloride (TTC) staining to assess the cerebral infarct volume. Then, we employed bioinformatics analysis and luciferase reporter assay to identify and validate the target molecule of miR-130a, PTEN. Results: Our findings indicated that miR-130a expression was lower in PC12 cells after OGDR (oxygen-glucose deprivation/reperfusion) and in rats after MCAO (middle cerebral artery occlusion). Moreover, ectopic-expression of miR-130a can significantly improve cell survival rate and reduce cell apoptosis and ROS production in PC12 cells after OGDR. In addition, re-expression of miR-130a yielded an obvious reduction in MCAO-induced infarct volume and neurological deficits in rats. Bioinformatics analysis revealed that PTEN was a miR-130a target and could overturn the effect of miR-130a on cerebral ischemia, both in vivo and in vitro. Therefore, we set out to further investigate the PTEN-affected PI3K/AKT pathway and found that upregulation of miR-130a activated the PI3K/AKT pathway. Conclusions: Our data demonstrated that miR-130a prevented cerebral I/R damage by mediating the PTEN/PI3K/AKT axis. These preliminarily findings furthered our understanding of this mechanism and identified new potential therapeutic targets for ischemic stroke.

CSFB has been adopted by many terminal manufacturers as one of the LTE voice solution. Restricted by CSFB mechanism，there exists one kind of GSM neighbor cell which is referred as shadow neighbor cell. Even without neighbor relations configured，shadow neighbor could lead UE（user equipment）to fall back successfully due to itsultra-long coverage and strong Rx level，and that would probably causes problems like dropped calls. Based on large data of road test and network of China Mobile Hangzhou Branch，the existence of shadow neighbor cell was pointed out，an optimization method of TD-LTE shadow neighbor cell was proposed，the hidden shadow neighbor cells were dug out，and they were eliminated by adjustments of antenna and frequency. Experimental results show that the method proposedis practical，effective and also worthy promotion.

The scientific coastline management is of great significance to the development of marine economy, coordinated development of land and marine and construction of ecological civilization. The coastline management in China has experienced two main stages: (i) the stage of basic survey and jurisprudential establishment, and (ii) the stage of perfection under new situation. There are challenges in promoting modern marine governance and marine power, which are characterized by the lack of high-quality management involvement throughout the coastline management process. Accordingly, coastline supervision is not comprehensive, the standardized system still needs to be improved, and the research on the main function of coastline has not been conducted yet. On this basis, the corresponding strategies were put forward from the perspectives of top-level design, main function, the “double-index” assessment system, requisition-compensation balance of natural coastline, with a view to provide strategic support for coastline management in China.

This paper studies the mineral materials’ adsorption properties of radioactive chemical elements, it takes the adsorption behavior of uranium (VI) by the synthetic ternary Ca-Mg-Al hydrotalcite as an example, starts from designing and assembling the highly acid-resistant hydrotalcite materials which contain various functional groups, successfully prepares three kinds of hydrotalcite materials by two basic processing technologies, then by using SEM, FT-IR, XPS and other surface technologies and conducting many adsorption experiments, this paper explores and studies the action mechanism and interface effect of the hydrotalcite materials’ adsorption of U(VI). Finally, it obtains relevant conclusions: a series of synthetic LDHs functional materials can be applied to the separation and concentration of radionuclides, and it is further confirmed that, during the U(VI) adsorption process, Ca-Mg-Al-LDH and Ca-Mg-Al-LDOx have surface complexation and electrostatic interaction, and the research results are of great significance for the development and use of efficient, cheap, and sustainable adsorbent materials in the future.

Environmentally benign Brønsted acidic ionic liquids with multi-SO3H functionality were prepared using N-methyl imidazole and 1,3-propane sultone as the source chemicals. The prepared ionic liquid catalysts were characterized by infrared (IR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy and thermogravimetry (TG) and their catalytic activity in esterification of caprylic acid with methanol was investigated. The results showed that the novel catalyst was very efficient for the reaction, with excellent water and acid resistant ability. Under optimum conditions, the yield of methyl caprylate reached 94.8%. The ionic liquids could be reused six times without a noticeable drop in activity. The kinetic study for the esterification indicated that the reaction order was 1.54 and the activation energy Ea was 24.61 kJ/mol.

As a renewable energy source, methane can not only improve ecological benefits and save energy, but also bring good economic benefits. In order to enhance the efficiency of methane preparation, the author used sodium acetate as the base material to study the effect of various mineral materials on microbial methane preparation. The results showed that mineral materials with good conductivity play a positive role in anaerobic microbial methane preparation, which is of referential meanings to highly-effective CH4 preparation.