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Regenerative endodontic procedures (REPs) are a new option for the treatment of dental pulp or periapical diseases in permanent teeth with open apices. Histologically, the new tissues formed in the root canal after REPs are mainly cementum- or bone-like mineralised tissues, but not the real dentine-pulp complex. Therefore, how to promote dentine-pulp complex regeneration and improve the clinical effects of REPs has become a prominent research topic. Stem cells from apical papilla (SCAP) are derived from the dental papilla that can differentiate into primary odontoblasts and dental pulp cells that produce root dentine and dental pulp. Exosomes are the key regulator for the paracrine activity of stem cells and can influence the function of recipient cells. In this study, SCAP-derived exosomes (SCAP-Exo) were introduced into the root fragment containing bone marrow mesenchymal stem cells (BMMSCs) and transplanted subcutaneously into immunodeficient mice. We observed that dental pulp-like tissues were present and the newly formed dentine was deposited onto the existing dentine in the root canal. Afterwards, the effects of SCAP-Exo on the dentinogenesis of BMMSCs were elucidated in vitro. We found that the gene and protein expression of dentine sialophosphoprotein and mineralised nodule formation in BMMSCs treated with SCAP-Exo were significantly increased. In summary, SCAP-Exo were endocytosed by BMMSCs and obviously improved their specific dentinogenesis. The use of exosomes derived from dental stem cells could comprise a potential therapeutic approach for dentine-pulp complex regeneration in REPs.

Silicon Photomultiplier (SiPM) is a sensor that can detect low-light signals lower than the single-photon level. In order to study the properties of neutrinos at a low detection threshold and low radioactivity experimental background, a low-temperature CsI neutrino coherent scattering detector is designed to be read by the SiPM sensor. Less thermal noise of SiPM and more light yield of CsI crystals can be obtained at the working temperature of liquid nitrogen. The breakdown voltage (Vbd) and dark count rate (DCR) of SiPM at liquid nitrogen temperature are two key parameters for coherent scattering detection. In this paper, a low-temperature test is conducted on the mass-produced ON Semiconductor J-Series SiPM. We design a cryogenic system for cooling SiPM at liquid nitrogen temperature and the changes of operating voltage and dark noise from room to liquid nitrogen temperature are measured in detail. The results show that SiPM works at the liquid nitrogen temperature, and the dark count rate drops by six orders of magnitude from room temperature (120 kHz/mm2) to liquid nitrogen temperature (0.1 Hz/mm2).

Abstract Background Tyrosine kinase receptor erythropoietin-producing hepatocellular receptor A2 (EphA2) is abundant in the endometrium and plays a role in the establishment of eutopic implantation. A similar molecular mechanism may exist between uterine implantation and tubal implantation, therefore EphA2 involvement in tubal pregnancy is suspected. Due to the limited availability of human Fallopian tube specimens, EphA2 expression in human Fallopian tube epithelium remains largely unknown. Methods A total of 31 women with tubal pregnancy and 41 non-pregnant women with benign uterine diseases were enrolled in this study. Immunohistochemistry was used to investigate the expression pattern of EphA2 in the Fallopian tube epithelium of non-pregnant women (n = 29) and women with tubal pregnancy (n = 17). The changes of EphA2 and its activated form, phosphorylated-EphA2 (Pho-EphA2), in the Fallopian tube epithelium from non-pregnant women (n = 12) and women with tubal pregnancy (n = 14) were compared by quantitative RT-PCR and western blot assay. Results EphA2 was expressed throughout the Fallopian tube epithelium, including the isthmus, the ampulla and the infundibulum. EphA2 concentration remained unchanged throughout the whole menstrual cycle, irrespective of menstrual phases and tubal regions. EphA2 mRNA in the Fallopian tube epithelium did not differ between normal women and women with tubal pregnancy (P > 0.05). With respect to the protein level, a significantly higher ratio of EphA2 over Pho-EphA2 was shown in women with tubal pregnancy (P

Background and Methods: To understand the burden and epidemiology of Streptococcus pneumoniae disease among children between 1 and 59 months of age in China, we conducted a review of literature published between 1980 and 2008 applying standardized algorithms. Because of the absence of population-based surveillance for pneumococcal disease (PD), we identified all-cause pneumonia, bacteremia and meningitis burden, syndromes most commonly associated with S. pneumoniae, and applied the proportion of disease attributable to S. pneumoniae from studies that determined the etiology of these three syndromes to calculate PD burden. Because of the microbiologic difficulties in identifying S. pneumoniae-attributable pneumonia which likely underestimates the pneumonia burden, we also used the proportion obtained from vaccine efficacy trials. Results: Between 1980 and 2008, there were 12,815 cases/100,000/year of all-cause pneumonia among children between 1 month and 59 months, with 526 deaths/100,000 annually. There were 14 meningitis cases/100,000/year. We estimate that as of 2000, there were 260,768 (113,000 to 582,382) and 902 (114-4,463) cases of pneumococcal pneumonia and meningitis, respectively with 10,703 (4,638-23,904) and 75 (9-370) pneumococcal pneumonia and meningitis deaths, respectively. Pneumococcal pneumonia cases and deaths were more than two-fold higher, 695,382 (173,845-1,216,918) and 28,542 (7,136-49,949), respectively, when parameters from efficacy trials were used. Serotypes 19F, 19A and 14 were the most common serotypes obtained from pneumonia/meningitis patients. Currently available vaccines are expected to cover 79.5% to 88.4% of the prevalent serotypes. With high antibiotic resistance, introducing pneumococcal vaccines to the routine immunization program should be considered in China. Population-based studies are warranted. [ABSTRACT FROM AUTHOR]

Objectives: We compare the evolution of electrode impedance values (IVs) following either conventional cochlear implantation or implantation by the soft surgery (SS) technique. Methods: We performed a retrospective chart review of 20 consecutive adult patients who underwent implantation with the Nucleus CA 24 device between 2004 and 2007. Five patients with preoperative residual hearing at the frequencies 256, 512, and 1,024 Hz underwent implantation by an SS cochlear implantation technique (SS group), and the 15 other patients underwent a conventional implantation technique (conventional cochleostomy [CC] group). The active electrodes were classified as distal (17 to 22), middle (10 to 16), or proximal (3 to 9) according to their position in relation to the tip of the electrode array. Their IVs were collected at 1,3,12,24, and 36 months after implantation. Changes in auditory thresholds at 3 and 24 months were reported for patients in the SS group. Results: The postoperative IVs of both the CC and SS groups decreased significantly between 1 and 3 months after implantation (p < 0.05) and then remained stable. The IVs after 12 months were significantly lower (p < 0.05) in the SS group than in the CC group. Conclusions: Patients who underwent the SS technique displayed lower long-term electrode IVs than did their counterparts in the CC group. If electrode IVs are indeed an indirect representation of cochlear fibrosis, the use of the SS technique in lieu of the CC technique could reduce fibrotic development. [ABSTRACT FROM AUTHOR]

This paper proposes an effective method of fault location based on a binary tree for optical burst switching (OBS) network. To minimize the monitoring cost, we divide the network into several monitor domains by introducing monitoring-cycle algorithms. In order to generate an exclusive code, we modify the monitoring cycle algorithm when two nodes have the same code. Through the binary tree algorithm, a pre-computation of faults in the OBS network can be achieved. When a fault happens, we can locate it immediately and accurately. Examples have proved that the algorithm has general applicability. [ABSTRACT FROM AUTHOR]

The dual pressure of energy crisis and environmental pollution has prompted the world’s energy sector to change in the direction of clean, efficient, sustainable and pollution-free, and RIES (Regional Integrated Energy System) has emerged. The deployment of energy storage devices in the RIES can deepen the connection of each energy system, release the spatial and temporal constraints of multiple energy sources, and thus improve the energy utilization and economy of the integrated energy system. Based on the infrastructure and model of the RIES, this paper studied the synergistic optimal configuration of electricity storage, power-to-gas (P2G) technology, cooling storage and heating storage in the case of multi-energy complementation operation of combined cooling, heating and power supply (CCHP) unit and other equipment. Firstly, an optimal configuration model of multiple energy storage in the RIES based on the optimal operational economy was proposed. Then, the economics and feasibility of configuring different energy storage combinations in the system were analyzed. Finally, the benefits of energy storage devices in the regional integrated energy system were quantified and analyzed by the economic indicators and low carbon emissions reduction indicators. By employing an industrial district RIES in northern China as the study case, the operation scheduling scheme and energy storage allocation scheme were solved by the optimization model proposed in this paper. The results show that the RIES containing multiple types of energy storage can consume more distributed new energy, improve economic efficiency and reduce carbon emissions. And this model has a good application prospect.

• Simultaneous identification and determination of three bioactive compounds in Amomum villosum samples. • After comparison of different spectra pretreatments, 2-Der with SNV was demonstrated as an optimum pretreatment. • The results show that the coefficients of determination are all above 0.96. PI approaching 100, RMSEC, RMSEP and RMSECV are under 0.6. • Excellent correlation between the GC determined value as well as the model-predicted value proved the feasibility of quantification and quality control of Amomum villosum with NIR models. A method is described using rapid and sensitive Fourier transform near-infrared spectroscopy combined with Gas Chromatograpy internal standard method detection for the simultaneous identification and determination of three bioactive compounds in Amomum villosum samples. Partial least squares regression is selected as the analysis type and multiplicative scatter correction, second derivative, and SNV were adopted for the spectral pretreatment. The correlation coefficients (R) of the calibration models were above 0.95 and the root mean square error of predictions were under 0.8. The developed models were applied to unknown samples with satisfantory results. The established method was validated and can be applied to the intrinsic quality control of Amomum villosum. [ABSTRACT FROM AUTHOR]

The relationship between structure and activity of theaflavins against human pancreatic α-Amylase was investigated by in vitro and in silico methods. The IC50 and total energy value showed that inhibitory effects followed the order: theaflavin-3, 3’-di-O-gallate > theaflavin-3’-O-gallate > theaflavin-3-O-gallate > theaflavin. Inhibitory activity was depended on hydroxyl groups and galloyl moieties of theaflavins to interact with the catalytic residues of the active site of α-Amylase by hydrogen bonds and π–π (aromatic–aromatic) interactions. The galloylated theaflavin has higher binding affinity with α-Amylase than non-galloylated theaflavin. The study showed that theaflavins might act as natural enzyme inhibitors with potential health benefits, which provide a foundation for designing novel functional food for effective controlling of starch digestion and postprandial glucose levels.

Both an excess of toxic lead (Pb) and an essential iron disorder have been implicated in many diseases and public health problems. Iron metabolism genes, such as the hemochromatosis (HFE) gene, have been reported to be modifiers for lead absorption and storage. However, the HFE gene studies among the Asian population with occupationally high lead exposure are lacking.To explore the modifying effects of the HFE genotype (wild-type, H63D variant and C282Y variant) on the Pb load and iron metabolism among Asian Pb-workers with high occupational exposure.Seven hundred and seventy-one employees from a lead smelter manufacturing company were tested to determine their Pb intoxication parameters, iron metabolic indexes and identify the HFE genotype. Descriptive and multivariate analyses were conducted.Forty-five H63D variant carriers and no C282Y variant carrier were found among the 771 subjects. Compared with subjects with the wild-type genotype, H63D variant carriers had higher blood lead levels, even after controlling for factors such as age, sex, marriage, education, smoking and lead exposure levels. Multivariate analyses also showed that the H63D genotype modifies the associations between the blood lead levels and the body iron burden/transferrin.No C282Y variant was found in this Asian population. The H63D genotype modified the association between the lead and iron metabolism such that increased blood lead is associated with a higher body iron content or a lower transferrin in the H63D variant. It is indicated that H63D variant carriers may be a potentially highly vulnerable sub-population if they are exposed to high lead levels occupationally.

Entangling multiple qubits is one of the central tasks of quantum information processing. We propose an approach to entangle a number of cold ions (individually trapped in a string of microtraps) by a moved cavity. The cavity is pushed to include the ions one by one with a uniform velocity and thus the information stored in former ions could be transferred to the latter ones by such a moving cavity bus. Since the positions of the trapped ions are precisely located, the strengths and durations of the ion-cavity interactions can be exactly controlled. As a consequence, by properly setting the relevant parameters, typical multi-ion entangled states, e.g., W state for 10 ions, could be deterministically generated. The feasibility of the proposal is also discussed. [ABSTRACT FROM AUTHOR]

Aiming at understanding the corrosion resistance of siloxane hydrolyzate cured cationic waterborne acrylic coatings, waterborne metal anti-corrosive coatings were prepared by cationic hydroxy acrylic resin dispersion containing tertiary amine group cured by siloxane hydrolysate WKHY-601.With using DSC, TGA, FT-IR and CHI660E electrochemical workstation, the curing mechanism of the coating and the main factors affecting its salt corrosion resistance were researched systematically.Results showed that the curing of the coating was achieved by the reaction of the silanol hydroxyl group and the alcohol hydroxyl group in the resin and the self-condensation of the siloxane hydrolyzate to form a cross-linked network.The content and type of the tertiary amine group in the resin and the amount of the curing agent siloxane hydrolyzate influenced the salt corrosion resistance of the coating film.As the content of tertiary amine groups increased, the self-corrosion potential of coating increased and the self-corrosion current density of coating declined.After reaching a certain level of the content of tertiary amine groups, the value remained stable.Besides, the dimethyl type tertiary amine group with less steric hindrance was better than the diethyl type, and the increase in the amount of siloxane hydrolyzate was beneficial to improve the compactness of the coating film and enhance its salt corrosion resistance.When the amount of siloxane hydrolyzate was excessive, the content of tertiary amine groups in the coating film would decrease, resulting in weakening the salt corrosion resistance.Furthermore, the self-corrosion potential of the coating sample prepared by DM type resin with a tertiary amine group content of 0.42 mmol/g and siloxane hydrolysate WKHY-601 according to a mass ratio of 3∶1 was as high as-0.298 V, and the self-corrosion current density was only 1.308×10-9 A/cm2, performing excellent salt corrosion resistance.

The objective of this paper is to predict the noise radiated from submarine propellers with different control surface types (the cross- and X-type). When the propellers are free from cavitation, such as those of submarines at a diving depth, the radiated noise dominate, due to unsteady propeller forces. A well-known submarine model (DARPA SUBOFF) is taken as the computing sample. Simulations for hydrodynamics, including stern wakes and unsteady propeller forces, are carried out by using CFD (Computational Fluid Dynamics) technology, and the results are compared with the experimental data. The accuracy of the predicted noise depends on the CFD results. Comparisons between the CFD results and the experimental data are in good agreement. The CFD results are treated as dipole strengths in the linear wave theory to predict the radiated noise caused by the unsteady forces of the propeller. It is found that, when the control surface is of the X-type, the propeller inflow is more uniform, and the radiated noise can be decreased by about 5 dB compared to the cruciform control surface. [ABSTRACT FROM AUTHOR]

The number of hearing-impaired people is increasing year by year; robotic cochlear drilling surgery is one of the safest methods to treat deafness. Looking at the issue of low efficiency of temporal bone posture positioning in cochlear implantation robotic drilling, a novel auxiliary ring marker temporal bone positioning method was proposed to improve temporal bone posture positioning efficiency, optimize the operation time, and reduce auxiliary injuries caused by the surgery. First, the temporal bone visual positioning assistant ring was designed based on the requirements for cochlear robotic drilling surgery. The target detection was conducted on the auxiliary ring and image processing and feature point extraction methods were designed. Then, the three-dimensional coordinates of the measured feature points were obtained by binocular vision, and the auxiliary ring and temporal bone postures were estimated. Finally, the auxiliary ring and temporal bone localization methods were validated. The experiment results indicated that the temporal bone was located quickly and effectively in a total time of about 33 ms, which was faster and more accurate than traditional visual localization methods and could satisfy real-time temporal bone localization during surgery. This study can reduce the time of temporal bone visual positioning in cochlear implant drilling operations, greatly improving the robot's capabilities to extract visual information during the operation, which has a better auxiliary role for future research and applications of the cochlear implant drilling operation. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the feasibility of a microscope-assisted endoscopic transcanal transpromontorial approach (METTA) for the removal of small vestibular schwannomas (VS) limited to the internal auditory canal (IAC), and introduce a modification without external auditory canal (EAC) closure. Methods: Between August 2018 and February 2019, seven patients with intrameatal VS underwent surgery in our center, endoscopic transcanal transpromontorial approach was applied in the first 2 patients and the rest 5 patients were operated via METTA. Treatment outcomes including efficacy of tumor resection, facial nerve outcome, operation time and post-operative course were recorded and analyzed. Results: All seven patients were pathologically confirmed to have intrameatal VS. Total tumor removal was achieved in all cases. Two patients experienced cerebrospinal fluid leakage which resolved spontaneously within 5 days. The average operation time was 161.41 ± 18.42 min. All patients presented normal facial nerve function 1 month after surgery. Conclusion: The METTA was effective in the removal of intrameatal VS. It can be an alternative surgical option for intrameatal VS with no serviceable hearing. [ABSTRACT FROM AUTHOR]

Background: Circulating regulatory T cells (Tregs) are responsible for mediating immune tolerance and maintaining immunological homeostasis. Decreases in Tregs may be involved in the onset of rheumatoid arthritis (RA). Low-dose interleukin-2 (IL-2) has been considered for the treatment of inflammatory diseases mediated by T cells. This study focused on the status of circulating CD4 + T subsets and the clinical feasibility of IL-2 therapies in patients with RA. Methods: The subjects included 888 patients with RA and 100 healthy controls (HCs); 233 RA patients received IL-2 treatment with 0.5 million international units (MIU)/day from days 1 through 5. The demographic features, disease activity, and levels of CD4+T cells measured by modified flow cytometry were collected in all RA patients before and after treatment. Results: RA patients had lower absolute Treg counts (but not Th17) compared with HCs, which was associated with disease activity; previously treated RA patients had the fewest circulating Tregs ( p

GTPase high frequency of lysogenization X (HflX) is highly conserved in prokaryotes and acts as a ribosome-splitting factor as part of the heat shock response in Escherichia coli. Here we report that HflX produced by slow-growing Mycobacterium bovis bacillus Calmette-Guérin (BCG) is a GTPase that plays a critical role in the pathogen's transition to a nonreplicating, drug-tolerant state in response to hypoxia. Indeed, HflX-deficient M. bovis BCG (KO) replicated markedly faster in the microaerophilic phase of a hypoxia model that resulted in premature entry into dormancy. The KO mutant displayed hallmarks of nonreplicating mycobacteria, including phenotypic drug resistance, altered morphology, low intracellular ATP levels, and overexpression of Dormancy (Dos) regulon proteins. Mice nasally infected with HflX KO mutant displayed increased bacterial burden in the lungs, spleen, and lymph nodes during the chronic phase of infection, consistent with the higher replication rate observed in vitro in microaerophilic conditions. Unlike fast growing mycobacteria, M. bovis BCG HlfX was not involved in antibiotic resistance under aerobic growth. Proteomics, pulldown, and ribo-sequencing approaches supported that mycobacterial HflX is a ribosome-binding protein that controls translational activity of the cell. With HflX fully conserved between M. bovis BCG and M. tuberculosis, our work provides further insights into the molecular mechanisms deployed by pathogenic mycobacteria to adapt to their hypoxic microenvironment. [ABSTRACT FROM AUTHOR]

Abstract Background The communication between carcinoma associated fibroblasts (CAFs) and cancer cells facilitate tumor metastasis. In this study, we further underlying the epigenetic mechanisms of CAFs feed the cancer cells and the molecular mediators involved in these processes. Methods MCF-7 and MDA-MB-231 cells were treated with CAFs culture conditioned medium, respectively. Cytokine antibody array, enzyme-linked immunosorbent assay, western blotting and immunofluorescence were used to identify the key chemokines. Chromatin immunoprecipitation and luciferase reporter assay were performed to explore the transactivation of target LncRNA by CAFs. A series of in vitro assays was performed with RNAi-mediated knockdown to elucidate the function of LncRNA. An orthotopic mouse model of MDA-MB-231 was conducted to confirm the mechanism in vivo. Results Here we reported that TGF-β1 was top one highest level of cytokine secreted by CAFs as revealed by cytokine antibody array. Paracrine TGF-β1 was essential for CAFs induced EMT and metastasis in breast cancer cells, which is a crucial mediator of the interaction between stromal and cancer cells. CAF-CM significantly enhanced the HOTAIR expression to promote EMT, whereas treatment with small-molecule inhibitors of TGF-β1 attenuated the activation of HOTAIR. Most importantly, SMAD2/3/4 directly bound the promoter site of HOTAIR, located between nucleotides -386 and -398, -440 and -452, suggesting that HOTAIR was a directly transcriptional target of SMAD2/3/4. Additionally, CAFs mediated EMT by targeting CDK5 signaling through H3K27 tri-methylation. Depletion of HOTAIR inhibited CAFs-induced tumor growth and lung metastasis in MDA-MB-231 orthotopic animal model. Conclusions Our findings demonstrated that CAFs promoted the metastatic activity of breast cancer cells by activating the transcription of HOTAIR via TGF-β1 secretion, supporting the pursuit of the TGF-β1/HOTAIR axis as a target in breast cancer treatment.

Cellular quiescence, a reversible state in which growth, proliferation, and other cellular activities are arrested, is important for self-renewal, differentiation, development, regeneration, and stress resistance. However, the physiological mechanisms underlying cellular quiescence remain largely unknown. In the present study, we used embryos of the crustacean Artemia in the diapause stage, in which these embryos remain quiescent for prolonged periods, as a model to explore the relationship between cell-membrane potential (Vmem) and quiescence. We found that Vmem is hyperpolarized and that the intracellular chloride concentration is high in diapause embryos, whereas Vmem is depolarized and intracellular chloride concentration is reduced in postdiapause embryos and during further embryonic development. We identified and characterized the chloride ion channel protein cystic fibrosis transmembrane conductance regulator (CFTR) of Artemia (Ar-CFTR) and found that its expression is silenced in quiescent cells of Artemia diapause embryos but remains constant in all other embryonic stages. Ar-CFTR knockdown and GlyH-101-mediated chemical inhibition of Ar-CFTR produced diapause embryos having a high Vmem and intracellular chloride concentration, whereas control Artemia embryos released free-swimming nauplius larvae. Transcriptome analysis of embryos at different developmental stages revealed that proliferation, differentiation, and metabolism are suppressed in diapause embryos and restored in postdiapause embryos. Combined with RNA sequencing (RNA-Seq) of GlyH-101-treated MCF-7 breast cancer cells, these analyses revealed that CFTR inhibition down-regulates the Wnt and Aurora Kinase A (AURKA) signaling pathways and upregulates the p53 signaling pathway. Our findings provide insight into CFTR-mediated regulation of cellular quiescence and Vmem in the Artemia model. [ABSTRACT FROM AUTHOR]

Apoptosis plays a critical role in normal embryonic development and tissue homeostasis regulation. EndophilinA2 (EndoA2) is widely reported to regulate endocytosis. Additionally, EndoA2 has been demonstrated to be involved in tumor metastasis, neuroregulation and vascular function. In this study, we used siRNA and Ad-EndoA2 transfection strategy to investigate whether EndoA2 provides a protective effect against apoptosis induced by H 2 O 2 in H9C2 cardiomyocytes and the underlying mechanisms. We found that EndoA2 siRNA knockdown promoted H 2 O 2 -induced apoptosis in H9C2 cardiomyocytes, evidenced by decreased cell number, increased apoptotic cells, and activation of caspase-3. In contrast, EndoA2 overexpression showed the opposite effects and inhibited H 2 O 2 -induced apoptosis in H9C2 cardiomyocytes. Further studies revealed that EndoA2 overexpression strengthened autophagy, evidenced by the increased LC3 II/I ratio and P62 degradation, whereas EndoA2 siRNA knockdown produced the opposite effects. Furthermore, we revealed that there was an interaction between Bif-1 and Beclin-1. Upon H 2 O 2 treatment, the association of Bif-1 and Beclin-1 remarkably increased. EndoA2 overexpression further promoted the binding of Bif-1 with Beclin-1, whereas EndoA2 siRNA knockdown reduced this association. These data strongly suggested that EndoA2 inhibited H 2 O 2 -induced apoptosis in H9C2 cardiomyocytes, possibly by promoting Bif-1 to form a complex with Beclin-1 and strengthening autophagy. This study provides a novel target for heart diseases. [ABSTRACT FROM AUTHOR]

A knowledge graph can effectively showcase the essential characteristics of data and is increasingly emerging as a significant means of integrating information in the field of artificial intelligence. Coronary artery plaque represents a significant etiology of cardiovascular events, posing a diagnostic challenge for clinicians who are confronted with a multitude of nonspecific symptoms. To visualize the hierarchical relationship network graph of the molecular mechanisms underlying plaque properties and symptom phenotypes, patient symptomatology was extracted from electronic health record data from real-world clinical settings. Phenotypic networks were constructed utilizing clinical data and protein‒protein interaction networks. Machine learning techniques, including convolutional neural networks, Dijkstra's algorithm, and gene ontology semantic similarity, were employed to quantify clinical and biological features within the network. The resulting features were then utilized to train a K-nearest neighbor model, yielding 23 symptoms, 41 association rules, and 61 hub genes across the three types of plaques studied, achieving an area under the curve of 92.5%. Weighted correlation network analysis and pathway enrichment were subsequently utilized to identify lipid status-related genes and inflammation-associated pathways that could help explain the differences in plaque properties. To confirm the validity of the network graph model, we conducted coexpression analysis of the hub genes to evaluate their potential diagnostic value. Additionally, we investigated immune cell infiltration, examined the correlations between hub genes and immune cells, and validated the reliability of the identified biological pathways. By integrating clinical data and molecular network information, this biomedical knowledge graph model effectively elucidated the potential molecular mechanisms that collude symptoms, diseases, and molecules., (© 2024. The Author(s).)

Pollution variation, source characteristics, and meteorological effects of water-soluble inorganic ions (WSIIs) in PM 2.5 were analyzed in Xinxiang city, Henan Province. PM 2.5 samples and their chemical components were monitored online by using URG-9000 in four seasons:winter (January, 2022), spring (April, 2022), summer (July, 2022), and fall (October, 2022). The results showed that the TWSIIs had the same seasonal fluctuations as PM 2.5 . The average seasonal concentrations of WSIIs ranged from 19.62-72.15 μg·m -3 , accounting for more than 60% of PM 2.5 , demonstrating that WSIIs were the major components of PM 2.5 . The annual concentration value of NO 3 - /SO 4 2- was 2.11, which showed an increasing trend, suggesting predominantly mobile sources for secondary inorganic aerosols (SNA). Further, the molar concentration value [NH 4 + ]/[NO 3 - ] was 1.95, demonstrating that agriculture emissions were the dominant contributors to atmospheric nitrogen. Furthermore, the backward trajectory analysis showed that the concentrations of Ca 2+ and Mg 2+ were higher when the northeasterly wind prevailed and the wind speed was high. High values of SOR and NOR were correlated with low temperatures and high relative humidity ( T < 8℃, RH > 60%), demonstrating that more gaseous precursors were converted into sulfate and nitrate. At high temperatures ( T > 24℃), there was no apparent high NOR value like that for SOR, mainly due to the decomposition of NH 4 NO 3 at high temperatures. Finally, backward trajectories associated with the PMF-resolved results were used to explore the regional transport characteristics. The results illustrated that dust sources in the study areas were mainly influenced by air trajectories originating from the northwest regions, whereas secondary sulfate, secondary nitrate, and biomass sources contributed more to WSIIs when wind speed and altitude air masses were low in the area surrounding the observation site.

Purpose: To investigate the value of serum free prostate-specific antigen density (fPSAD) in the diagnosis of prostate cancer (PCa)., Methods: The data of 558 patients who underwent transrectal ultrasound-guided prostate biopsy were retrospectively analyzed. According to the pathological results, the patients were divided into a PCa group and a benign prostatic hyperplasia (BPH) group. Receiver operating characteristic curves were plotted, based on which the sensitivity, specificity, Youden index, concordance, and kappa values of free prostate-specific antigen (fPSA), the free-to-total f/tPSA, prostate-specific antigen density (PSAD), the free-to-total (f/t)/PSAD ratio, and fPSAD were compared. The patients were divided into three groups by PSA levels (PSA < 4 ng/mL, PSA = 4-10 ng/mL, and PSA > 10 ng/mL), into three groups by age (age < 60 year, age = 60-80y, and age > 80 years), and into two groups by prostate volume (PV) (PV ≤ 80 mL and PV > 80 mL) to compare the sensitivity, specificity, and concordance of indicators., Results: tPSA, PSAD, (f/t)/PSAD, and fPSAD had high accuracy in predicting PCa with AUC values of 0.820, 0.900, 0.846, and 0.867. fPSAD showed lower diagnostic sensitivity but significantly higher specificity and concordance for PCa than tPSA, f/tPSA, (f/t)/PSAD, or PSAD. Thus, fPSAD had the highest accuracy in the diagnosis of PCa. In the groups with different PSA, age, and PV stratification, the concordance of fPSAD was significantly higher (88.61%, 90.74%, and 90.38%) than that of other indicators., Conclusion: With the optimal cutoff value of 0.062, fPSAD has a higher diagnostic value for PCa than tPSA, f/tPSA, (f/t)/PSAD, and PSAD, and can well predict the risk of PCa, significantly improve the clinical diagnostic rate of PCa, and reduce unnecessary biopsy., (© 2023. The Author(s).)

Background/aim: Hypertensive nephropathy (HN) is a common complication of hypertension. Traditional Chinese medicine has long been used in the clinical treatment of Hypertensive nephropathy. However, botanical drug prescriptions have not been summarized. The purpose of this study is to develop a prescription for improving hypertensive nephropathy, explore the evidence related to clinical application of the prescription, and verify its molecular mechanism of action. Methods: In this study, based on the electronic medical record data on Hypertensive nephropathy, the core botanical drugs and patients' symptoms were mined using the hierarchical network extraction and fast unfolding algorithm, and the protein interaction network between botanical drugs and Hypertensive nephropathy was established. The K-nearest neighbors (KNN) model was used to analyze the clinical and biological characteristics of botanical drug compounds to determine the effective compounds. Hierarchical clustering was used to screen for effective botanical drugs. The clinical efficacy of botanical drugs was verified by a retrospective cohort. Animal experiments were performed at the target and pathway levels to analyze the mechanism. Results: A total of 14 botanical drugs and five symptom communities were obtained from real-world clinical data. In total, 76 effective compounds were obtained using the K-nearest neighbors model, and seven botanical drugs were identified as Gao Shen Formula by hierarchical clustering. Compared with the classical model, the Area under the curve (AUC) value of the K-nearest neighbors model was the best; retrospective cohort verification showed that Gao Shen Formula reduced serum creatinine levels and Chronic kidney disease (CKD) stage [OR = 2.561, 95% CI (1.025-6.406), p < 0.05]. With respect to target and pathway enrichment, Gao Shen Formula acts on inflammatory factors such as TNF-α, IL-1β, and IL-6 and regulates the NF-κB signaling pathway and downstream glucose and lipid metabolic pathways. Conclusion: In the retrospective cohort, we observed that the clinical application of Gao Shen Formula alleviates the decrease in renal function in patients with hypertensive nephropathy. It is speculated that Gao Shen Formula acts by reducing inflammatory reactions, inhibiting renal damage caused by excessive activation of the renin-angiotensin-aldosterone system, and regulating energy metabolism., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Huan, Ma, Li, Hu, Chen, Wang, Su, Su and Wang.)

Object: To explore the effects of occupational aluminum exposure on workers' cognitive function and blood glucose concentration, and to analyze whether blood glucose concentration can mediate the cognitive changes caused by aluminum., Method: Our study recruited 375 workers from an aluminum factory in northern China. We collected the fasting elbow venous blood of the workers, measured their fasting blood glucose concentration (FBG), and used ICP-MS to determine plasma aluminum concentration (P-Al) as an indicator of internal exposure. The Montreal Cognitive Assessment (MoCA), was used to assess the cognitive function of workers. Generalized linear model was used to analyze the association of P-Al with cognitive function and blood glucose concentration, and the restricted cubic spline model was used to fit the dose-response relationship. We also conducted a mediation effect analysis., Result: We observed the dose-response relationship, that is, as the P-Al increased, sum of MoCA, visuospatial/executive, naming, language, and abstraction scores decreased, and the blood glucose concentration increased. For every e-fold increase in P-Al, sum of MoCA, visuospatial/executive, naming, language, and abstraction scores decreased by 0.328 points, 0.120 points, 0.059 points, 0.060 points, and 0.083 points, respectively, and FBG rose by 0.109 mmol/L. FBG has a significant mediating effect between P-Al and sum of MoCA (P for mediator=0.042), and it could explain 10.7% of the effect of cognitive level related to P-Al., Conclusion: Occupational aluminum exposure negatively affected the cognitive function of workers and positively affected FBG. FBG may partially explain the impact of occupational aluminum exposure on workers' cognitive function., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Hypertension and coronary heart disease are the most common cardiovascular diseases, and traditional Chinese medicine is applied as an auxiliary treatment for common cardiovascular diseases. This study is based on 3 years of electronic medical record data from the Affiliated Hospital of Shandong University of Traditional Chinese Medicine. A complex network and machine learning algorithm were used to establish a screening model of coupled herbs for the treatment of hypertension complicated with coronary heart disease. A total of 5688 electronic medical records were collected to establish the prescription network and symptom database. The hierarchical network extraction algorithm was used to obtain core herbs. Biological features of herbs were collected from public databases. At the same time, five supervised machine learning models were established based on the biological features of the coupled herbs. Finally, the K-nearest neighbor model was established as a screening model with an AUROC of 91.0%. Seventy coupled herbs for adjuvant treatment of hypertension complicated with coronary heart disease were obtained. It was found that the coupled herbs achieved the purpose of adjuvant therapy mainly by interfering with cytokines and regulating inflammatory and metabolic pathways. These results show that this model can integrate the molecular biological characteristics of herbs, preliminarily screen combinations of herbs, and provide ideas for explaining the value in clinical applications., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Jia-Ming Huan et al.)

This study analyzed the seasonal variation, sources, and source-specific health risks of PM 2.5 -bound metals in Xinxiang city, Henan province. A total of 112 daily PM 2.5 samples were collected over four consecutive seasons during 2019-2020. In total, 19 elements were identified using inductively coupled plasma atomic emission spectroscopy (ICP-AES). The annual concentrations of PM 2.5 and 11 heavy metals were calculated to be (66.25±35.73) μg·m -3 and (1.32±0.84) μg·m -3 , respectively. Strong seasonal variations were observed in PM 2.5 concentrations and the concentrations of associated metal elements, with the lowest concentrations all occurring in summer. The highest concentrations of dust-related elements (e.g., Al, Ca, Fe, Mg,and Ti) were recorded in spring, differing significantly from other elements, which all exhibited the highest mass concentrations in winter. The results apportioned from positive matrix factorization (PMF) and potential source contribution function (PSCF) models showed that the major sources of PM 2.5 -bound elements were Ni-and Co-related emissions (5.8%), motor vehicles (13.7%), Cd-related emissions(5.1%), combustion emissions (18.2%), and dust (57.3%). Health risk models showed that there were no obvious non-carcinogenic risks associated with these metals, because their hazard quotient (HQ) values were all below 1. Lifetime carcinogenic risks of the five apportioned sources were all higher than the acceptable level (1×10 -6 ). Of these five sources, combustion emissions were the largest contributors to cancer risk (8.74×10 -6 , 36.9%) and non-cancer risk (0.60, 25.6%). This study suggests that control strategies to mitigate exposure risk in Xinxiang should emphasize reducing the sources of combustion emissions.

Objective: To obtain the subtypes of the clinical hypertension population based on symptoms and to explore the relationship between hypertension and comorbidities., Methods: The data set was collected from the Chinese medicine (CM) electronic medical records of 33,458 hypertension inpatients in the Affiliated Hospital of Shandong University of Traditional Chinese Medicine between July 2014 and May 2017. Then, a hypertension disease comorbidity network (HDCN) was built to investigate the complicated associations between hypertension and their comorbidities. Moreover, a hypertension patient similarity network (HPSN) was constructed with patients' shared symptoms, and 7 main hypertension patient subgroups were identified from HPSN with a community detection method to exhibit the characteristics of clinical phenotypes and molecular mechanisms. In addition, the significant symptoms, diseases, CM syndromes and pathways of each main patient subgroup were obtained by enrichment analysis., Results: The significant symptoms and diseases of these patient subgroups were associated with different damaged target organs of hypertension. Additionally, the specific phenotypic features (symptoms, diseases, and CM syndromes) were consistent with specific molecular features (pathways) in the same patient subgroup., Conclusion: The utility and comprehensiveness of disease classification based on community detection of patient networks using shared CM symptom phenotypes showed the importance of hypertension patient subgroups., (© 2021. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Hypertensive nephropathy is a common complication of hypertension. Traditional Chinese medicine has been used in the clinical treatment of hypertensive nephropathy for a long time, but the commonly used prescriptions have not been summarized, and the basic therapeutic approaches have not been discussed. Based on data from 3 years of electronic medical records of traditional Chinese medicine used at the Affiliated Hospital of Shandong University of Traditional Chinese Medicine, a complex network and machine learning algorithm was used to explore the prescribed herbs of traditional Chinese medicine in the treatment of hypertensive nephropathy (HN). In this study, complex network algorithms were used to describe traditional Chinese medicine prescriptions for HN treatment. The Apriori algorithm was used to analyze the compatibility of these treatments with modern medicine. Data on the targets and regulatory genes related to hypertensive nephropathy and the herbs that affect their expression were obtained from public databases, and then, the signaling pathways enriched with these genes were identified on the basis of their participation in biological processes. A clustering algorithm was used to analyze the therapeutic pathways at multiple levels. A total of 1499 prescriptions of traditional Chinese medicines used for the treatment of hypertensive renal damage were identified. Fourteen herbs used to treat hypertensive nephropathy act through different biological pathways: huangqi, danshen, dangshen, fuling, baizhu, danggui, chenpi, banxia, gancao, qumai, cheqianzi, ezhu, qianshi, and niuxi. We found the formulae of these herbs and observed that they could downregulate the expression of inflammatory cytokines such as TNF, IL1B, and IL6 and the NF- κ B and MAPK signaling pathways to reduce the renal inflammatory damage caused by excessive activation of RAAS. In addition, these herbs could facilitate the deceleration in the decline of renal function and relieve the symptoms of hypertensive nephropathy. In this study, the traditional Chinese medicine approach for treating hypertensive renal damage is summarized and effective treatment prescriptions were identified and analyzed. Data mining technology provided a feasible method for the collation and extraction of traditional Chinese medicine prescription data and provided an objective and reliable tool for use in determining the TCM treatments of hypertensive nephropathy., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this article., (Copyright © 2021 Jia-Ming Huan et al.)

Cardiac hypertrophy is one of the major risk factors for chronic heart failure. The role of endophilinA2 (EndoA2) in clathrin-mediated endocytosis and clathrin-independent endocytosis is well documented. In the present study, we tested the hypothesis that EndoA2 protects against angiotensin II (Ang II)-induced cardiac hypertrophy by mediating intracellular angiotensin II type 1 receptor (AT1-R) trafficking in neonatal rat cardiomyocytes (NRCMs). Cardiac hypertrophy was evaluated by using cell surface area and quantitative RT-PCR (qPCR) analyses. For the first time, we found that EndoA2 attenuated cardiac hypertrophy and fibrosis induced by Ang II. Moreover, EndoA2 inhibited apoptosis induced by excessive endoplasmic reticulum stress (ERS), which accounted for the beneficial effects of EndoA2 on cardiac hypertrophy. We further revealed that there was an interaction between EndoA2 and AT1-R.The expression levels of EndoA2, which inhibits AT1-R transport from the cytoplasm to the membrane, and the interaction between EndoA2 and AT1-R were obviously decreased after Ang II treatment. Furthermore, Ang II inhibited the co-localization of AT1-R with GRP-78, which was reversed by EndoA2 overexpression. In conclusion, our results suggested that EndoA2 plays a role in protecting against cardiac hypertrophy induced by Ang II, possibly by inhibiting AT1-R transport from the cytoplasm to the membrane to suppress signal transduction., (© 2018 Wiley Periodicals, Inc.)

Following the recent emergence of Zika virus (ZIKV), many murine and human neutralizing anti-ZIKV antibodies have been reported. Given the risk of virus escape mutants, engineering antibodies that target mutationally constrained epitopes with therapeutically relevant potencies can be valuable for combating future outbreaks. Here, we applied computational methods to engineer an antibody, ZAb&#95;FLEP, that targets a highly networked and therefore mutationally constrained surface formed by the envelope protein dimer. ZAb&#95;FLEP neutralized a breadth of ZIKV strains and protected mice in distinct in vivo models, including resolving vertical transmission and fetal mortality in infected pregnant mice. Serial passaging of ZIKV in the presence of ZAb&#95;FLEP failed to generate viral escape mutants, suggesting that its epitope is indeed mutationally constrained. A single-particle cryo-EM reconstruction of the Fab-ZIKV complex validated the structural model and revealed insights into ZAb&#95;FLEP's neutralization mechanism. ZAb&#95;FLEP has potential as a therapeutic in future outbreaks., (Copyright © 2018. Published by Elsevier Inc.)

Objective: To observe the effect of Naoxintong Capsule (NC) on the vascular endothelial function and the infarct size of patients with acute myocardial infarction (AMI)., Methods: One hundred and four patients with AMI were randomly assigned to the NC group (Group A, 36 cases), the Tongguan Capsule group (Group B, 32 cases), and the conventional Western medicine group (Group C, 36 cases). The conventional Western medicine was given to the three groups. NC was additionally given to Group A, and Tongguan Capsule was additionally given to Group B. The therapeutic course for all was 4 weeks. The plasma nitric oxide (NO), endothelin (ET), von Willebrand factor (vWF) were detected in the 3 groups before and after treatment. The inner diameter of brachial artery was examined by ultrasonograph. The flow-mediated dilation (FMD) and the nitroglycerin-mediated dilation (NMD) were calculated. The ECG QRS integral and the infarct size were assessed., Results: There was no significant difference in the vascular endothelial function, ECG QRS integral, or the infarct size among the three groups before treatment (P > 0.05). Compared with before treatment, NO and NMD obviously increased after treatment in Group A and Group B, while the vWF and the infarct size obviously decreased in Group A, all showing statistical difference (P < 0.05). Compared with those in Group C, the NO, FMD, NMD significantly increased and ET obviously decreased in Group A and B after treatment (P < 0.05). The ECG QRS integral and the infarct size also decreased, with statistically significant differences in Group A (P < 0.05). Better effects on improving NO, NMD, and vWF were obtained in Group A than in Group B (P < 0.05)., Conclusion: NC could reduce the infarct size of AMI patients possibly through improving the vascular endothelial function.

Objective: To explore the risk factors and the main TCM syndrome types associated with the diabetes mellitus type 2 (DM2) patients complicated with non-alcoholic fatty liver (FL)., Methods: Adopted controlled trial method, the age, stature, body weight, and body mass index (BMI) of 180 DM2 patients were compared with those complicated with or without FL. And some related laboratory indexes, including the age, stature, body weight, BMI, fasting blood glucose (FBG), C-peptide (CP), glycosylated hemoglobin (HbA1c), triglyceride (TG), total cholesterol (TC), high and low density lipoprotein cholesterol (HDL-C and LDL-C), and 2 h post-prandial CP (2 h CP), were compared as well. Moreover, patients' TCM syndrome types were classified., Results: No significant differences were found between DM2 patients complicated with or without FL in aspects of FBG, HbA1c, TC, LDL-C and age, stature (P > 0.05), but significant difference did show between them in aspects of CP (4.09 +/- 2.40 microg/L vs 2.47 +/- 1.74 microg/L), 2h CP (6.38 +/- 5.46 microg/L vs 4.35 +/- 2.92 microg/L), TG (2.81 +/- 2.33 mmol/L vs 1.93 +/- 1.92 mmol/L), HDL-C (1.07 +/- 0.06 mmol/L vs 1.19 +/- 0.32 mmol/L) as well as in body weight (73.4 +/- 11.7 kg vs 61.4 +/- 10.1 kg) and BMI (26.0 +/- 3.67 vs 22.8 +/- 3.23), respectively (P < 0.05 or P < 0.01). Moreover, phlegm-dampness type was more liable to appear in DM2 patients complicated FL., Conclusions: Obesity, insulin resistance and lipid metabolism disorder are the chief risk factors in DM2 patients complicated with FL and phlegm-dampness is the chief pathogenesis.