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Objective To investigate the clinical effect of Gancao Ganjiang Decoction (GGD) combined with moxibustion on the patients with end-stage renal disease (ESRD) received maintenance peritoneal dialysis (PD). Methods Sixty-two ESRD patients received maintenance PD in the First Hospital of Hebei Medical University from June 2019 to June 2021 were selected and were randomly divided into control group and treatment group (n=31, each). The routine western medicine was given in control group, while the modified GGD combined with Yiqi Huiyuan moxibustion was added in treatment group based on the routine western medicine. After 4 weeks of treatment, the TCM syndrome scores, the dialysis adequacy ［serum creatinine (Scr), blood urea nitrogen (BUN), uric acid, estimated glomerular filtration rate (eGFR),residual renal function (RRF), residual renal urea clearance index (KT/V) and PD KT/V parameters］ and the cardiac injury biomarkers ［serum amino-terminal brain natriuretic peptide (NT-proBNP), creatine kinase-myocardial band (CK-MB), cardiac troponin Ⅰ (cTnⅠ) levels］ were observed and compared between two groups. Cardiovascular adverse events were observed during 6 months follow-up period. Results After treatment, TCM syndromes scores in treatment group were statistically lower than those in control group (P

Organic molecules containing seven-membered rings are important structural motifs for drug candidates, but the construction of seven-membered rings can be challenging through traditional cyclization pathways. Here, the authors report a copper-catalyzed alkyne oxidation and Büchner-type ring-expansion to generate benzo[6,7]azepino[2,3-b]quinolines and pyridine-based diones.

Fruit firmness is an important quality trait of apple fruit texture, and the pre-harvest ripening period is the key period for the formation of apple fruit texture. Expansin is a cell wall loosing protein family that has four subfamilies: α-expansin (EXPA), β-expansin (EXPB), expansin-like A (EXLA), and expansin-like B (EXLB). In this study, we investigated the key period of pre-harvest texture formation in ‘Golden Delicious’ apples based on fruit longitudinal diameter, transverse diameter, firmness, tissue structure, respiration intensity, ethylene release rate, and expansin activity. Within the 10 days before harvest, the fruit was found to reach maturity. Semi-quantitative RT-PCR revealed that most of the expansins were expressed at the ripening stage before harvest. The biological function of the EXLB subfamily gene, MdEXLB1, was further identified, and its subcellular localization on the cell wall was confirmed by transient transformation experiments. Compared with the wild type (WT), the transgenic tomato lines overexpressing MdEXLB1 had lower plant height, earlier fruiting period, fewer days for fruit ripening, higher fruit maturity, lower fruit firmness, higher fruit expansin activity, more discrete flesh cell structure, and accelerated fruit ripening process. Overall, this is the first study to propose that the apple EXLB subfamily gene, MdEXLB1, has biological functions and plays an important role in promoting fruit ripening and softening.

The authors introduce an active-mode optical microcavity sensor with enhanced sensitivity via Förster resonant energy transfer. Changes in lasing wavelengths of both donor and acceptor enable quantitative molecular analysis and real-time monitoring of intracellular molecules.

Automatic text summarization can help people to filter and identify information quickly,grasp the key content of news,and alleviate the problem of information overload.The mainstream abstractive summarization model is mainly based on the encoder-decoder architecture.In view of the fact that the decoder does not fully consider the text topic information when predicting the target word,and the traditional Word2Vec static word vector cannot solve the polysemy problem,an automatic summarization model for Chinese short news is proposed,which integrates the BERT word embedding representation and topic information enhancing.The encoder combines unsupervised algorithm to obtain text topic information and integrates it into the attention mechanism to improve the decoding effect of the model.At the decoder side,the BERT sentence vector extracted from the BERT pre-trained language model is used as the supplementary feature to obtain more semantic information.Meanwhile,pointer mechanism is introduced to solve the problem of out of vocabulary,and coverage mechanism is used to suppress repetition effectively.Finally,in the training process,reinforcement learning method is adopted to optimize the model for non-differentiable index ROUGE to avoid exposing bias.Experimental results on two datasets of Chinese short news summarization show that the proposed model can significantly improve the ROUGE evaluation index,effectively integrate text topic information,and generate fluent and concise summaries.

Although the complete nucleotide sequence of strawberry vein banding virus (SVBV) has been determined and bioinformatic analysis has revealed that the SVBV genome could encode seven proteins, the precise function of each protein is unclear. This study provided evidence that the P1 protein of SVBV (SVBV-P1) possesses the following features. Bioinformatic and subcellular localization analyses showed that SVBV-P1 is localized in the cytoplasm and cell walls of epidermal cells in Nicotiana benthamiana, and it forms inclusion bodies associated with microtubules and the endoplasmic reticulum. Dilution experiments demonstrated that SVBV-P1 could move from the original agro-infiltrated cells to adjacent cells in N. benthamiana leaves. Further trans-complementation experiments demonstrated that SVBV-P1 could facilitate the intercellular movement of a movement-deficient potato virus X mutant in N. benthamiana leaves. Finally, yeast two-hybrid and bimolecular fluorescence complementation assays revealed that SVBV-P1 could interact with the SVBV coat protein, which is a major component of Caulimovirus virions. Results of the electrophoretic mobility shift assay indicated that SVBV-P1 lacks DNA-binding capability. In summary, the results suggest that SVBV-P1 is probably a movement protein of SVBV, providing new insights into the function of movement proteins of the Caulimovirus genus.

Ascorbate peroxidase (APX) plays a key role in scavenging reactive oxygen species (ROS) in higher plants. However, there is very little information available on the APXs in kiwifruit (Actinidia), which is an economically and nutritionally important horticultural crop with exceptionally high ascorbic acid (AsA) accumulation. This study aims to identify and characterize two cytosolic APX genes (AcAPX1 and AcAPX2) derived from A. chinensis ‘Hongyang’. The constitutive expression pattern was determined for both AcAPX1 and AcAPX2, and showed relatively higher expression abundances of AcAPX1 in leaf and AcAPX2 in root. Transcript levels of AcAPX1 and AcAPX2 were increased in kiwifruit roots treated with NaCl. Subcellular localization assays using GFP-fusion proteins in Arabidopsis protoplasts showed that both AcAPX1 and AcAPX2 are targeted to the cytosol. Recombinant AcAPX1 or AcAPX2 proteins were successfully expressed in the prokaryotic expression system and their individual ascorbate peroxidase activities were determined. Finally, constitutive over-expression of AcAPX1 or AcAPX2 could dramatically increase total AsA, glutathione level and salinity tolerance under NaCl stress in Arabidopsis thaliana. Our findings revealed that cytosolic AcAPX1/2 may play an important protective role in the responses to unfavorable environmental stimuli in kiwifruit.

Abstract Purpose The current study aimed to optimize the culture and production parameters of industrial production of lincomycin A by Streptomyces lincolnensis using a statistical approach that could also reduce unwanted by-products. Methods The Plackett-Burman design, steepest ascent method, and response surface design were used to evaluate different factors that affect lincomycin A production. Results Using an optimized S. lincolnensis fermentation medium, lincomycin A production was increased up to 4600 mg/L in shaking flasks, which indicated a 28.3% improvement over previous production in an un-optimized medium (3585 mg/L). Additionally, the concentration of lincomycin B by-product was reduced to 0.8%, which was 82.2% lower than that in the un-optimized medium. Further, quantitative real-time PCR analysis revealed the optimized medium improved lincomycin A production by stimulating key genes in the lincomycin A biosynthesis pathway, as well as an osmotic stress gene. Conclusions Based on the results, the sequential optimization strategy in this study provides powerful means for the enhancement of lincomycin A with less by-product. We found that osmotic stress reduced the concentration of lincomycin B, which could also help reduce fermentation by-product yields in other actinobacteria.

Objective To investigate the effect of sulforaphane on ischemia-reperfusion injury(I/RI) and the role of PI3K/Akt/GSK-3β pathway in heart transplantation of rats. Methods The rat model of allograft heart transplantation was established as the control group.The survival rate,the level of serum myocardial enzymes,apoptosis of myocardial cells and the swelling degree of myocardial mitochondria were compared with sulforaphane injection group (2.5 mg/kg).Western blot was used to detect the expression of apoptotic molecules caspase-3,Bax and PI3K/Akt/GSK-3β. Results The survival rate of sulforaphane group was significantly higher than that of control group(P＜0.05).The serum concentrations of LDH,CK,CK-MB and TNT in sulforaphane group were lower than those in control group with a time dependent manner at different treatment time (6,12,24 and 48 h).The expressions of caspase-3 and Bax were significantly decreased (P＜0.01),and the degree of mitochondrial swelling was also improved compared with the control group. Conclusions Sulforaphane may inhibit myocardial apoptosis by activating PI3K/Akt/GSK-3β pathway and improve I/RI after heart transplantation as shown by animal model.

Based on the hexagonal honeycomb structure and the tri-ligament chiral honeycomb structure, this paper proposes a hybrid material structure with low-frequency elastic wave suppression below 100 Hz. Based on the finite element method and Bloch's theorem, the energy band structure was calculated, and the formation of the band gap and the wave-propagation properties of the structure were carefully studied, the wave attenuation performance of the composite structure was simulated, and the influence of material properties and geometric parameters on the width and position of the band-gap distribution was discussed. The results show that the structure can generate a good band gap in the low-frequency range of 100 Hz, and the wave propagation is suppressed obviously. Demonstrating its potential in practical applications, the research in this paper provides a theoretical basis for the manufacture of low-frequency vibration damping equipment and instruments, and provides a scheme for the design of metamaterials with low-frequency band gaps. [ABSTRACT FROM AUTHOR]

Scutellarin, one of natural flavonoids from Scutellaria barbata D. Don and Erigeron breviscapus (vant) Hand.-Mazz. Modern pharmacological studies have shown that scutellarin has a good anti-tumor effect. According to the literature review at home and abroad, scutellarin can inhibit the growth and metastasis of tumor cells, block the cell cycle at various stages, induce apoptosis and autophagy, interfere with tumor metabolism, reverse drug resistance of tumor cells and enhance the sensitivity of chemotherapy drugs. In this paper, the anti-tumor mechanism of scutellarin was reviewed, and the shortcomings of current studies and future research directions were analyzed, so as to provide a basis for further exploration of the anti-tumor potential of scutellarin and its further development and utilization. [ABSTRACT FROM AUTHOR]

Common unsupervised feature selection methods only consider the selection of discriminative features,while ignoring the redundancy of features and failing to consider the problem of small classes,which affect the classification performance.Based on this background,a robust uncorrelated regression algorithm is proposed.First,research on uncorrelated regression,use uncorrelated orthogonal constraints to find irrelevant but discriminative features.Uncorrelated constraints keep the data structure in the Stiefel manifold,making the model have a closed solution,avoiding the possible trivial solutions caused by the traditional ridge regression model.Secondly,the loss function and the regularization term use the L2,1 norm to ensure the robustness of the model and obtain a sparse projection matrix.At the same time,the small class problem is taken into account,so that the number of projection matrices is not limited by the number of classes,and the result is enough projection matrices to improve the classification performance of the model.Theoretical analysis and experimental results on multiple data sets show that the proposed method has better performance than other feature selection methods.

Background: The treatment of bone defects remains a clinical challenge. The effect of negative pressure wound therapy (NPWT) on osteogenesis in bone defects has been recognized; however, bone marrow fluid dynamics under negative pressure (NP) remain unknown. In this study, we aimed to examine the marrow fluid mechanics within trabeculae by computational fluid dynamics (CFD), and to verify osteogenic gene expression, osteogenic differentiation to investigate the osteogenic depth under NP.Methods: The human femoral head is scanned using micro-CT to segment the volume of interest (VOI) trabeculae. The VOI trabeculae CFD model simulating the bone marrow cavity is developed by combining the Hypermesh and ANSYS software. The effect of trabecular anisotropy is investigated, and bone regeneration effects are simulated under NP scales of −80, −120, −160, and −200 mmHg. The working distance (WD) is proposed to describe the suction depth of the NP. Finally, gene sequence analysis, cytological experiments including bone mesenchymal stem cells (BMSCs) proliferation and osteogenic differentiation are conducted after the BMSCs are cultured under the same NP scale.Results: The pressure, shear stress on trabeculae, and marrow fluid velocity decrease exponentially with an increase in WD. The hydromechanics of fluid at any WD inside the marrow cavity can be theoretically quantified. The NP scale significantly affects the fluid properties, especially those fluid close to the NP source; however, the effect of the NP scale become marginal as WD deepens. Anisotropy of trabecular structure coupled with the anisotropic hydrodynamic behavior of bone marrow; An NP of −120 mmHg demonstrates the majority of bone formation-related genes, as well as the most effective proliferation and osteogenic differentiation of BMSCs compared to the other NP scales.Conclusion: An NP of −120 mmHg may have the optimal activated ability to promote osteogenesis, but the effective WD may be limited to a certain depth. These findings help improve the understanding of fluid mechanisms behind NPWT in treating bone defects.

BackgroundA variety of autoantibodies have been detected in primary biliary cholangitis (PBC), while the presence of autoantibody clusters and their clinical significance have not been fully understood. We aimed at defining autoantibody clusters and to better understand the clinical features and prognosis of PBC patients based on autoantibody clusters under real-world conditions.MethodsWe retrospectively analyzed 788 inpatients with PBC evaluated between October 2008 and July 2019, and included 537 patients. Nineteen autoantibodies which were measured routinely were investigated for cluster analysis. Two-step clustering, Kaplan-Meier survival, and Cox regression analyses were used.ResultsFive clusters were defined. A cluster of antinuclear antibodies (ANA) and anti-gp210 positive patients were identified with a high rate of cirrhosis at baseline and low survival rate; a cluster of ANA, anti-centromere antibodies (ACA) and/or anti-CENP-B female dominant patients with older disease onset, low level of platelet count at baseline, high rate of hepatic decompensation, and low survival rate was also characterized; and another cluster of anti-mitochondrial antibodies (AMA) and/or AMA-M2, anti-Ro52 and a high rate of anti-gp210 positive patients were identified with a high proportion of male patients and low survival rate. A subgroup of patients with anti-SSA and/or anti-SSB coexists with SjS was also identified; patients with only AMA and/or AMA-M2-positive with a benign clinical outcome and relatively high complication of non-alcoholic fatty liver disease (NAFLD) were also identified. Only anti-gp210 was considered as a significant predictor for poor outcomes especially in patients with cirrhosis.ConclusionClustering methods allow the identification of distinct autoantibody profiles of PBC that form clinical subsets and can be useful for personalized approaches to diagnosis, clinical management, and the prediction of clinical outcomes. Anti-gp210 was the strongest predictive factor for poor outcomes especially in PBC patients with cirrhosis under real-world conditions.

Abstract Aurora A kinase is a cell cycle regulator that is dysregulated in several different malignancies. Nevertheless, its regulatory mechanisms are still not fully understood. Here, we report that ubiquitin specific peptidase 3 (USP3) promotes proliferation and metastasis of esophageal squamous cell carcinoma (ESCC) cells by mediating deubiquitination of Aurora A. Analysis of human clinical samples indicated that USP3 and Aurora A are highly expressed in ESCC. Cellular experiments confirmed that high expression of USP3 and Aurora A in ESCC cells promoted malignant cell proliferation and invasion. In this mechanism, USP3 leads to suppression of Aurora A ubiquitination, resulting less proteasome degradation. We constructed the deubiquitinated mimetic K143R of Aurora A and found that K143R significantly promoted the proliferation and invasion of ESCC cells and was not regulated by the deubiquitination of USP3. Moreover, Aurora A K143R potentiated the kinase activity of Aurora A in ESCC cells. Thus, our findings demonstrate that the tumorigenic feature of ESCC is in part mediated by USP3-facilitated deubiquitination of Aurora A.

Background: The aim of this study was to analyze clinical features and short-term mortality in hemodialysis (HD) patients infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) omicron BA.2.2.1 variant. Methods: In a retrospective single-center case series, 102 consecutive hospitalized HD patients infected with the coronavirus omicron variant were assessed at Pudong Hospital in Shanghai, China, from April 6 to April 18, 2022; the final date of follow-up was May 16, 2022. Clinical, laboratory, chest CT, and treatment data were collected and analyzed. The association between these factors and all-cause mortality was studied using univariate and multivariate analyses. The relationship between lymphocyte count and short-term mortality was based on receiver operating characteristic (ROC) curve analysis. Kaplan–Meier analysis was used to assess overall survival. Results: In total, 102 patients were included in this study. The patients were divided into two groups: HD patients with pneumonia (N = 46) and without pneumonia (N = 56). Of the 102 patients, 12 (11.8%) died. Multivariate regression analysis revealed that all-cause mortality was correlated with lymphocyte counts and type B natriuretic peptide (BNP), C-reactive protein (CRP), and D-dimer levels (P

BackgroundLaryngeal cancer (LC) is a prevalent head and neck malignancy; however, the essential pathophysiological mechanism underlying its tumorigenesis and progression remains elusive. Due to the perduring scarcity of effective targeted drugs for laryngeal cancer, insights into the disease’s pathophysiological mechanisms would substantially impact the treatment landscape of laryngeal cancer.MethodsTo ensure quality consistency, 10 tumor and 9 non-tumor samples underwent proteomic analysis on a single mass spectrometer using a label-free technique. Subsequently, gene expression variations between laryngeal squamous cell carcinoma and normal tissues were analyzed using The Cancer Genome Atlas (TCGA) database. Immunohistochemical expressions of insulin-like growth factor 2 receptor (IGF2R), fibronectin (FN), vimentin, and α-smooth muscle actin (SMA) in LC tissues and normal tissues were determined.ResultsIn the tumor group, significant variations were detected for 433 upregulated and 61 downregulated proteins. Moreover, the heatmap revealed that the expressions of RNA translation-related proteins and proteins involved in RNA metabolism, such as IGF2R, tenascin C (TNC), periostin (POSTN), proteasome 26S subunit ATPase 4 (PSMC4), serpin family A member 3 (SERPINA3), heat shock protein family B (small) member 6 (HSPB6), osteoglycin (OGN), chaperonin containing TCP1 subunit 6A (CCT6A), and chaperonin containing TCP1 subunit 6B (CCT6B), were prominently elevated in the tumor group. Nonsense-mediated RNA decay (NMD), RNA translation, and protein stability were significantly altered in LC tumors. IGF2R was remarkably upregulated in LC tumors. In the TCGA database, the IGF2R mRNA level was significantly upregulated in LSCC tissues. Additionally, IGF2R mRNA expression was lowest in clinical grade 1 samples, with no significant difference between grades 2 and 3. In LSCC patients, a significant positive correlation between IGF2R expression and the stromal score was detected using the ESTIMATE algorithm to estimate the immune score, stromal score, and tumor purity in the tumor microenvironment. Lastly, immunohistochemical analysis revealed that IGF2R is overexpressed in LC.ConclusionThese results demonstrate the vital role of IGF2R in LC carcinogenesis and progression and may facilitate the identification of new therapeutic targets for the prevention and treatment of LC.

BackgroundThe human leukocyte antigen (HLA) susceptibility gene is the main genetic risk factor for primary biliary cholangitis (PBC). The prognosis of patients with PBC is linked to gut microbiota dysbiosis. However, whether the HLA alleles are associated with the gut microbiota distribution and disease severity remains unknown.MethodsA cohort of 964 Chinese patients with PBC was enrolled at Beijing YouAn Hospital, Beijing, China. High-resolution genotyping of the HLA class I and class II loci from 151 of these patients was performed using sequence-based PCR. Stool samples were collected from 43 of the 151 fully HLA-typed patients to analyze their microbiota compositions via 16S RNA gene sequencing.ResultsOf the 964 patients, the male:female ratio was 114:850, and 342 of these patients (35.5%) had already developed liver cirrhosis (LC) before enrollment. Patients with PBC showed a significantly higher frequency of HLA DRB1*08:03 than did the controls (21.2% vs. 9.0%, P=0.0001). HLA-DRB1*03:01, DRB1*07:01, DRB1*14:05, and DRB1*14:54 frequencies were also increased but did not reach significance after Bonferroni’s correction. Conversely, the DQB1*03:01 frequency was significantly lower in patients with PBC than in the controls (24.5% vs. 39.2%, P=0.0010). The patients’ gut microbiota were analyzed from four perspectives. The microbial community abundances were significantly lower in FHRAC-positive patients (patients with a combination of five HLA DRB1 high-risk alleles) than in FHRAC-negative patients (P

Diabetic kidney disease (DKD) is the leading cause of end‐stage renal disease. However, because of shared complications between DKD and chronic kidney disease (CKD), the description and characterization of DKD remain ambiguous in the clinic, hindering the diagnosis and treatment of early‐stage DKD patients. Although estimated glomerular filtration rate and albuminuria are well‐established biomarkers of DKD, early‐stage DKD is rarely accompanied by a high estimated glomerular filtration rate, and thus there is a need for new sensitive biomarkers. Transcriptome profiling of kidney tissue has been reported previously, although RNA sequencing (RNA‐Seq) analysis of the venous blood platelets in DKD patients has not yet been described. In the present study, we performed RNA‐Seq analysis of venous blood platelets from three patients with CKD, five patients with DKD and 10 healthy controls, and compared the results with a CKD‐related microarray dataset. In total, 2097 genes with differential transcript levels were identified in platelets of DKD patients and healthy controls, and 462 genes with differential transcript levels were identified in platelets of DKD patients and CKD patients. Through Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, we selected 11 pathways, from which nine potential biomarkers (IL‐1B, CD‐38, CSF1R, PPARG, NR1H3, DDO, HDC, DPYS and CAD) were identified. Furthermore, by comparing the RNA‐Seq results with the GSE30566 dataset, we found that the biomarker KCND3 was the only up‐regulated gene in DKD patients. These biomarkers may have potential application for the therapy and diagnosis of DKD, as well aid in determining the mechanisms underlying DKD.

Ellagic acid (EA) is a dietary polyphenol that widely exists in grapes, strawberries, and walnuts. It usually exerts multiple biological activities together with its in vivo metabolites called urolithins. EA and urolithins had been proposed as natural agents for applying on the early intervention of Alzheimer’s disease (AD). However, the neuroprotective effects of those small molecules have not been confirmed, and the action mechanism is not clear. Deposition of beta-amyloid (Aβ) protein is well documented as being involved in the initiation and pathological process of AD. In the present study, we investigated the attenuating effects of EA and several urolithins on Aβ25–35-induced neuronal injury and its underlying molecular mechanism by constructing the in vitro AD cell model of PC12 cells and primary neurons. The results revealed that EA and urolithins especially the UM5 and UM6 exerted promising neuroprotective effects in improving the Aβ25–35-induced cell damage and lactate dehydrogenase (LDH) leakage, reducing reactive oxygen species (ROS) production, inhibiting neuronal apoptosis, and promoting neurite outgrowth. These results provide new insights into the development of UM5 and UM6 as anti-AD candidates. A network pharmacology analysis combining molecular docking strategy was further adopted to predict the signaling pathway involved in the anti-AD action of EA and urolithins, and the activation of PI3K-Akt, as well as the inhibition of MAPK was found to be involved.

Background Somnipathy and diabetes are independently associated with an increased risk of cardiovascular disease (CVD). However, whether a combination of both conditions is associated with a higher risk of CVD events remains uncertain. Therefore, the aim of this meta‐analysis was to clarify this association. Methods and Results We searched MEDLINE, Web of Science, EMBASE, ClinicalTrials.gov, and the Cochrane Central Register for Controlled Trials. We included randomized controlled trials, nonrandomized trials, and prospective observational cohort studies that assessed the combined effect of diabetes and comorbid somnipathy on CVD risk and mortality for at least 1 year. Outcomes included CVD, coronary heart disease, stroke, and all‐cause mortality. Twelve studies involving 582 267 participants were included in the meta‐analysis. Patients with somnipathy and comorbid diabetes exhibited increased risks of CVD, coronary heart disease, stroke, and all‐cause mortality (risk ratio [RR], 1.27 [95% CI, 1.12–1.45], P

Abstract Background Niemann-Pick C disease is a rare autosomal recessive lysosomal lipid storage disorder. Some primary immunodeficiency diseases patients developed regional disease or disseminated disease after vaccinating BCG. It is unclear whether NPC gene deficiency is associated with Mycobacteria infection. Case presentation We report and discuss a case of a child who presented at the age of 6 months with NPC1 and BCG-itis. The patient was treated with Miglustat and the symptom of lymphadenopathy was improved. Conclusions We reasonably speculate that NPC1 is a susceptibility gene of Mtb infection and mainly affects innate immunity. Once diagnosed, the infant should not be vaccinated with BCG and early treated.