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In recent years, skin spectral information has been gradually applied in various fields, such as the cosmetics industry and clinical medicine. However, the high price and the huge size of the skin spectrum measurement device make the related applications of the skin spectrum unable to be widely used in practical applications. We used convolutional neural network (CNN) to achieve a satisfying accuracy of the Fitzpatrick skin-type classification by using a simple self-developed device in 2018. Leveraging on the hardware, firmware, and software app-developing experience, a low-cost miniature skin spectrum measurement system (LMSSMS) using deep neural network (DNN) technology was further studied, and the feasibility of the system is verified in this paper. The developed LMSSMS is divided into three parts: (1) miniature skin spectrum measurement device (MSSMD), (2) DNN model, and (3) mobile app. The MSSMD was developed with innovative low-cost MSSC, 3D printing, and a simple LED light source. The DNN model is designed to enhance measurement accuracy. Finally, the mobile app is used to control and show the measurement results. The developed app also includes a variety of skin-spectrum-related applications, such as erythema index and melanin index (EI/MI) measurement, Fitzpatrick skin-type classification, Pantone SkinTone classification, sun-exposure estimation, and body-fat measurement. In order to verify the feasibility of LMSSMS, we used the standard instrumentation device as a reference. The results show that the accuracy of the LMSSMS can reach 94.7%, which also confirms that this development idea has much potential for further development.

BACKGROUND: Prompt pathogen identification can have a substantial impact on the optimization of antimicrobial treatment. The objective of the study was to assess the diagnostic value of next-generation sequencing (NGS) for identifying pathogen and its clinical impact on antimicrobial intervention in immunocompromised patients with suspected infections. METHODS: This was a retrospective study. Between January and August 2020, 47 adult immunocompromised patients underwent NGS testing under the following clinical conditions: 1) prolonged fever and negative conventional cultures; 2) new-onset fever despite empiric antimicrobial treatment; and 3) afebrile with suspected infections on imaging. Clinical data, including conventional microbial test results and antimicrobial treatment before and after NGS, were collected. Data were analyzed according to documented changes in antimicrobial treatment (escalated, no change, or deescalated) after the NGS results. RESULTS: The median time from hospitalization to NGS sampling was 19 d. Clinically relevant pathogens were detected via NGS in 61.7% of patients (29/47), more than half of whom suffered from fungemia (n=17), resulting in an antimicrobial escalation in 53.2% of patients (25/47) and antimicrobial de-escalation in 0.2% of patients (1/47). Antimicrobial changes were mostly due to the identification of fastidious organisms such as Legionella, Pneumocystis jirovecii, and Candida. In the remaining three cases, NGS detected clinically relevant pathogens also detected by conventional cultures a few days later. The antimicrobial treatment was subsequently adjusted according to the susceptibility test results. Overall, NGS changed antimicrobial management in 55.3% (26/47) of patients, and conventional culture detected clinically relevant pathogens in 14.9% of the patients (7/47). CONCLUSION: With its rapid identification and high sensitivity, NGS could be a promising tool for identifying relevant pathogens and enabling rapid appropriate treatment in immunocompromised patients with suspected infections. [ABSTRACT FROM AUTHOR]

Objective: For determination of how ADAMTS9-AS1/miR-301b-3p/TGFBR2/JAK STAT signaling axis modulates progression of breast cancer cells.Methods: Target lncRNA was determined by differential analysis of breast cancer expression data and survival analysis. Differentially expressed miRNAs and target mRNAs that had binding sites with target lncRNA were predicted. GSEA software was used to carry out pathway enrichment analysis for mRNAs. Binding of the researched genes were tested with RNA binding protein immunoprecipitation (RIP). How miR-301b-3p bound TGFBR2 mRNA was tested by dual-luciferase method. Transwell, colony formation, EdU approaches were employed for verification of invasion and proliferation of breast cancer cells in each treatment group.Results: Markedly inactivated ADAMTS9-AS1 in breast cancer pertained to patient’s prognosis. MiR-301b-3p was capable of binding TGFBR2/ADAMTS9-AS1. However, overexpression of ADAMTS9-AS1 stimulated miR-301b-3p binding ADAMTS9-AS1 and repressed miR-301b-3p binding TGFBR2 mRNA. ADAMTS9-AS1 interference enhanced cancer proliferation and invasion, facilitated levels of KI67, PCNA, MMP-9 and MMP-2, and activated the JAK STAT signaling pathway. While silencing miR-301b-3p reversed the effect of ADAMTS9-AS1 interference. In addition, TGFBR2 interference or restraining JAK STAT signaling counteracted the effect of ADAMTS9-AS1.Conclusion: ADAMTS9-AS1 could sequester miR-301b-3p to inhibit progression of breast cancer via TGFBR2/JAK STAT pathway. This study supplies a rationale for incremental apprehension of ADAMTS9-AS1 in breast cancer progression.

Abstract Aberrant metabolisms have been hypothesized to precede the occurrence of hepatocellular carcinoma (HCC), therefore, we investigated biomarkers associated with subsequent HCC in peripheral bloods using metabolomic technologies. A cohort of 475 HCC-naïve liver cirrhotic patients were recruited and prospectively followed. A total of 39 patients developed HCC in the follow-up period. Baseline plasma metabolites were explored using untargeted nuclear magnetic resonance. Candidates were then quantified by ultra-performance liquid chromatography. A series of univairiate and multivariate analysis showed that Phenylalanine (Phe) and Glutamine (Gln) levels are associated with time to HCC, independent of viological etiologies and age. A HCC risk score R was then constructed using the polynomial combination of age, Phe and Gln in the units of micromolar (μM):$$\begin{aligned} {\text{R }} & = {\text{ Age }}* \, \left( {0.0694} \right) + {\text{ Phe }}* \, \left( {0.3399} \right) + {\text{ Phe }^{2}}* \, \left( { - 0.00188154} \right) \hfill \\ & \quad + {\text{ Gln }}* \, \left( { - 0.0133} \right) + {\text{ Gln }^{2}}* \, \left( { \, 0.00002244} \right) \hfill \\ \end{aligned}$$ R=Age∗0.0694+Phe∗0.3399+Phe2∗-0.00188154+Gln∗-0.0133+Gln2∗0.00002244 R correlates with the time to HCC significantly (Hazard ratio [HR] = 2.368, 95% confidence interval [CI] 1.760–3.187, P

Abstract Background Team-based learning (TBL) is increasingly being utilized across medical fields by engaging students in small group discussions. The readiness assurance test (RAT) is an essential feature that differentiates TBL from problem-based learning (PBL) activity sequences. No publication has discussed differences in the RAT in TBL in medical schools. The purpose of this meta-analysis study was to examine the performance of learners in terms of group RAT (GRAT) and individual RAT (IRAT) scores in TBL for students of healthcare professions. Methods Databases, including PubMed and Cochrane were searched using several terms. We assessed the quality of included studies and conducted a meta-analysis. Results In total, 11 studies with 1575 participants were identified. Quality assessment scores of these studies ranged 4 ~ 7. Mean GRAT scores were significantly higher than mean IRAT scores (standardized mean difference (SMD) = 2.027, 95% confidence interval (CI) = 1.657 ~ 2.486, p heterogeneity < 0.001). Although the test of subgroup differences was insignificant (p = 0.113), the nursing-only subgroup showed much better performance in the GRAT than the IRAT (SMD = 2.3CI: 95% CI = 2.0 ~ 2.6, I 2 = 48.77%) compared to the others subgroup which included students from different majors. The subgroup analysis explained the heterogeneity in the overall analysis. Because of inadequate information from these 11 studies, a meta-regression could not explore the source of heterogeneity in terms of the mean age, duration of the intervention, preparation time before the RAT, and previous TBL experienced by students. Conclusions Students achieved significantly higher scores for the GRAT than for the IRAT, especially the group which only included nursing students, which implies excellent collaboration in the group of nursing students.

With next generation networks driving the confluence of multi-media, broadband, and broadcast services, Cognitive Radio (CR) networks are positioned as a preferred paradigm to address spectrum capacity challenges. CRs address these issues through dynamic spectrum access. However, the main challenges faced by the CR pertain to achieving spectrum efficiency. As a result, spectrum efficiency improvement models based on spectrum sensing and sharing models have attracted a lot of research attention in recent years, including CR learning models, network densification architectures, and massive Multiple Input Multiple Output (MIMO), and beamforming techniques. This paper provides a survey of recent CR spectrum efficiency improvement models and techniques, developed to support ultra-reliable low latency communications that are resilient to surges in traffic and competition for spectrum. These models and techniques, broadly speaking, enable a wide range of functionality ranging from enhanced mobile broadband to large scale Internet of Things (IoT) type communications. In addition and given the strong correlation between the typical size of a spectrum block and the achievable data rate, the models studied in this paper are applicable in ultra-high frequency band. This study therefore provides a good review of CRs and direction for future investigations into newly identified 5G research areas, applicable in industry and in academia.

Abstract Bimetallic nanomaterials, which exhibit a combination of the properties associated with two different metals, have enabled innovative applications in nanoscience and nanotechnology. Here, we introduce the fabrication of dendritic Au/Ag bimetallic nanostructures for surface-enhanced Raman scattering (SERS) and catalytic applications. The dendritic Au/Ag bimetallic nanostructures were prepared by combining the electrochemical deposition and replacement reaction. The formation of Au nanoparticle shell on the surface of Ag dendrites greatly improves the stability of dendritic nanostructures, followed by a significant SERS enhancement. In addition, these dendritic Au/Ag bimetallic nanostructures are extremely efficient in degrading 4-nitrophenol (4-NP) compared with the initial dendritic Ag nanostructures. These experimental results indicate the great potential of the dendritic Au/Ag bimetallic nanostructures for the development of excellent SERS substrate and highly efficient catalysts.

We report the use of environmental samples to assess avian influenza virus activity in chickens at live poultry markets in China. Results of environmental and chicken samples correlate moderately well. However, collection of multiple environmental samples from holding, processing, and selling areas is recommended to detect viruses expected to have low prevalence.

Objective To investigate the expression heterogeneity of transforming growth factor⁃β⁃induced protein (TGFBI) in glioblastoma (GBM) multiform and the mechanism of its promotion on malignancy of glioma stem cells (GSCs) in vitro. Methods Using The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), REMBRANDT and Oncomine database to analyse the potential associations between grades, subtypes, overall survival (OS) of GBM and the expression level of TGFBI and the correlation between TGFBI and tumor⁃associated macrophages (TAMs) marker CD11b and CD163. Treating human monocytes cell line U937 with sequential peripheral blood mononuclear cells and IL⁃4 to get Primed⁃and M2⁃TAMs, quantitative real⁃time polymerase chain reaction (qRT⁃PCR) were used to detect the expression level of markers for M1 ⁃, M2 ⁃ TAMs and TGFBI. Performing immunofluorescent and immunohistochemical stain to reveal the distribution of TGFBI, M2⁃TAMs and GSCs in specimen of GBM patients, adding rhTGFBI to the culture medium to see its impacts on the sphere formation and invasion capacity of NCH⁃421K. Results According to the RNA⁃seq and microarray data of GBM patients in each database, expression level of TGFBI positively correlated to GBM grades and negatively to OS, Futhermore, expression level of TGFBI were strongly correlate with either pan TAMs marker CD11b or M2⁃TAMs marker CD163, and as the induction of U937⁃derived M2⁃TAMs, the expression level of M2⁃TAMs marker and TGFBI increased accompanied by decreasingly M1⁃TAMs marker. Also, we found an obvious co⁃location between TGFBI and CD163, SOX2 in frozen and paraffin sections of GBM specimens. Lastly, we demonstrate that rhTGF86BI could enhance the sphere formation and invasion capacity of NCH⁃421K in vitro. Conclusions M2⁃TAMs secrete TGFBI to promote the sphere formation and invasion capacity of GSCs in GBM. DOI：10.3969/j.issn.1672⁃6731.2019.12.006

Background/purpose(s): Enterovirus D68(EV-D68) is an emerging disease that affects mostly children. There have been few relevant investigations to clarify transmission and seroprevalence within daycares and kindergartens. Methods: This prospective cohort study investigated respiratory viral transmission among preschool children in a public kindergarten in Taipei City of Taiwan between September 2006 and June 2008. After children were enrolled, daily monitoring of illness and regular biweekly physical examinations were performed. We performed viral isolation to detect acute EV-D68 infection and neutralization tests to detect specific EV-D68 antibodies and to measure the seroprevalence and seroconversion rates. Results: Among 190 kindergarten attendees aged between two to five years old, nine children had acute EV-D68 infection in September 2007. The clinical manifestations included pharyngitis, cough and other unspecified upper respiratory tract infection. None of the infected children had acute flaccid paralysis or severe respiratory illness. The phylogenetic tree of partial viral protein 3 and viral protein 1 was clustered in clade A1. The EV-D68 seropositive rate increased from 19% (25/130) at the beginning to 67% (83/124) at the end of the study. The seroconversion rate of 49 children with initial seronegative and paired sera was 73% (36/49). Conclusions: A high seroconversion rate (73%) for EV-D68 was found among kindergarten attendees, which indicates preschool-aged children are highly susceptible to EV-D68 infection and that the disease burden may be extremely underestimated. Once EV-D 68 circulates, preventive measures may be advocated, especially within kindergartens or daycares, to reduce transmission and subsequent development of severe cases. Keywords: Enterovirus D68, Kindergarten attendees, Manifestation, Seroconversion

Abstract Background Spinocerebellar ataxia type 3 (SCA3) is the most common subtype of autosomal dominantly inherited spinocerebellar ataxias (SCAs). No validated blood biomarker is available to assess either disease progression or therapeutic response. Neurofilament light chain (NfL) was recently proposed as a serum biomarker for many neurodegenerative disorders. The present study investigated whether NfL was a promising serum biomarker for SCA3. Methods Seventeen SCA3 patients and 9 controls were enrolled in cohort A, and 116 SCA3 individuals (preclinical and patients) and 91 controls were recruited as cohort B. We assessed whether serum NfL correlated with cerebrospinal fluid (CSF) NfL in cohort A and correlations between serum NfL levels and clinical features and brain volumes were determined in cohort B. The single-molecule array method was used to measure serum NfL levels. Disease severity was determined using the scale for the assessment and rating of ataxia (SARA) and the international cooperative ataxia rating scale (ICARS). Cerebellar and brainstem volumes were assessed using MRI neuroimaging measurements. Results Serum/CSF NfL levels in cohort A were elevated in SCA3 patients, and serum and CSF NfL exhibited a significant positive correlation (r = 0.9179, p

Abstract Spinocerebellar ataxia (SCA) type 1 (SCA1) is a rare autosomal dominant disorder that is characterized by worsening of disordered coordination, ataxia of the trunk, and other neurological symptoms. Physical activity improves both mobility and the daily living activities of patients with SCA. Intervention with daily regular treadmill exercise may slow the deterioration of cerebellar neurons in SCA1. Therefore, the signal changes and performance of cerebellar neurons after exercise in SCA1 was investigated in this study. We employed a transgenic mouse model of SCA1, generated by amplifying the cytosine‐adenine‐guanine trinucleotide repeat expansions, and the mice underwent 1 month of moderate daily treadmill exercise for 1 hour. The rotarod test revealed that the motor function of the SCA1 mice that underwent training was superior to that of the control SCA1 mice, which did not undergo training. Moreover, the cerebellar pathology revealed preserved Purkinje neurons stained by carbindin with an increase of the neuronal Per Arnt Sim domain protein 4, a key regulation in the structural and functional plasticity of neurons, in the excised SCA1 mice relative to the controls. The mechanism was related to an increase of phosphorylation of ribosomal protein S6, a downstream target of the mammalian target of rapamycin pathway, but not to autophagy activation. This study determined that regular treadmill exercise may play a crucial role in the viable support of cerebellar neurons in SCA1.

Immune cells are shaped by the tissue environment, yet the states of healthy human T cells are mainly studied in the blood. Here, the authors perform single cell RNA-seq of T cells from tissues and blood of healthy donors and show its utility as a reference map for comparison of human T cell states in disease.

Traditional seawater desalination requires high amounts of energy, with correspondingly high costs and limited benefits, hindering wider applications of the process. To further improve the comprehensive economic benefits of seawater desalination, the desalination load can be combined with renewable energy sources such as solar energy, wind energy, and ocean energy or with the power grid to ensure its effective regulation. Utilizing energy internet (EI) technology, energy balance demand of the regional power grid, and coordinated control between coastal multi-source multi-load and regional distribution network with desalination load is reviewed herein. Several key technologies, including coordinated control of coastal multi-source multi-load system with seawater desalination load, flexible interaction between seawater desalination and regional distribution network, and combined control of coastal multi-source multi-load storage system with seawater desalination load, are discussed in detail. Adoption of the flexible interaction between seawater desalination and regional distribution networks is beneficial for solving water resource problems, improving the ability to dissipate distributed renewable energy, balancing and increasing grid loads, improving the safety and economy of coastal power grids, and achieving coordinated and comprehensive application of power grids, renewable energy sources, and coastal loads. Keywords: Desalination, Distribution network, Power grids, Multi-source multi-load, Coordinated control

Objective: To investigate the prognostic value of phenylalanine and leucine in patients with severe infection. Methods: Ninety-three patients with infection who had a quick Sequential Organ Failure Assessment (qSOFA) score ≥2 were enrolled. Plasma phenylalanine, leucine, albumin, C-reactive protein, pre-albumin, and transferrin were measured and the SOFA score at enrollment was calculated after hospitalization. Results: During the 3-month follow-up, 30 (32.3%) patients died. Death was associated with higher SOFA scores, a higher incidence of bacteremia and admission to the intensive care unit, higher C-reactive protein and phenylalanine levels, worse kidney function, and lower pre-albumin and transferrin levels. Patients were categorized into three groups: high-risk type 1 (phenylalanine ≥84 μM), high-risk type 2 (phenylalanine

In the past, most research focused on the children living near a typical contaminated area but ignored the health risks of children living in the fourth or fifth tier cities without typical contaminated sources. These cities are now facing a series of problems, such as serious environmental pollution, undeveloped health system and so on. Furthermore, the development of modern logistics for food delivery has altered lifestyles that directly impact diets and eating patterns. In this study, multiple exposure pathways and health risks of children to heavy metal(loid)s were studied based on questionnaire-based surveys and field sampling of soil, dust, fine particulates, drinking water and food. We found that Pb, Cd and Mn levels in environmental samples were very high indicating a serious pollution problem. Inhalation exposure via aerosol particles was the most important pathway and was greater than exposure by food ingestion. The hazard index for Mn via aerosol particles was >1 even at the 5th percentile and Mn levels in urine was 10 times higher than those of people living in typical contaminated areas. The total incremental lifetime cancer risk (ILCR) for all metal(loid)s was also higher than the threshold at the 95th percentile. This study highlights health risks to children living in fourth tier cities and the importance of air pollution control to protect heavy metal exposure for children. Keywords: Heavy metal(loid)s, Fourth tier cities, Exposure pathways, Health risk, Children

Abstract Background Bronchial carcinoids are neuroendocrine tumors that present as typical (TC) and atypical (AC) variants, the latter being more aggressive, invasive and metastatic. Studies of tumor initiating cell (TIC) biology in bronchial carcinoids has been hindered by the lack of appropriate in-vitro and xenograft models representing the bronchial carcinoid phenotype and behavior. Methods Bronchial carcinoid cell lines (H727, TC and H720, AC) were cultured in serum-free growth factor supplemented medium to form 3D spheroids and serially passaged up to the 3rd generation permitting expansion of the TIC population as verified by expression of stemness markers, clonogenicity in-vitro and tumorigenicity in both subcutaneous and orthotopic (lung) models. Acetazolamide (AZ), sulforaphane (SFN) and the AZ + SFN combination were evaluated for targeting TIC in bronchial carcinoids. Results Data demonstrate that bronchial carcinoid cell line 3rd generation spheroid cells show increased drug resistance, clonogenicity, and tumorigenic potential compared with the parental cells, suggesting selection and expansion of a TIC fraction. Gene expression and immunolabeling studies demonstrated that the TIC expressed stemness factors Oct-4, Sox-2 and Nanog. In a lung orthotopic model bronchial carcinoid, cell line derived spheroids, and patient tumor derived 3rd generation spheroids when supported by a stroma, showed robust tumor formation. SFN and especially the AZ + SFN combination were effective in inhibiting tumor cell growth, spheroid formation and in reducing tumor formation in immunocompromised mice. Conclusions Human bronchial carcinoid tumor cells serially passaged as spheroids contain a higher fraction of TIC exhibiting a stemness phenotype. This TIC population can be effectively targeted by the combination of AZ + SFN. Our work portends clinical relevance and supports the therapeutic use of the novel AZ+ SFN combination that may target the TIC population of bronchial carcinoids.

Lung adenocarcinoma (LUAD) is a prevalent cancer killer. Investigation on potential prognostic markers of LUAD is crucial for a patient’s postoperative planning. LUAD-associated datasets were acquired from Gene Expression Omnibus (GEO) as well as The Cancer Genome Atlas (TCGA). LUAD metabolism-associated differentially expressed genes were obtained, combining tumor metabolism-associated genes. COX regression analyses were conducted to build a five-gene prognostic model. Samples were divided into high- and low-risk groups by the established model. Survival analysis displayed favorable prognosis in the low-risk group in the training set. Favorable predictive performance of the model was discovered as hinted by receiver’s operative curve (ROC). Survival analysis and ROC analysis in the validation set held an agreement. Gene Set Enrichment Analysis (GSEA), tumor mutation bearing (TMB), and immune infiltration differential analysis were performed. The two groups displayed differences in glycolysis gluconeogenesis, P53 signaling pathway, etc. The high-risk group showed higher TP53 mutation frequency as well as TMB. The low-risk group displayed higher immune activity along with immune score. Altogether, this study casts light on further development of novel prognostic markers for LUAD.

The leading implementers of the curriculum and educational system are teachers, so the success and failure of the educational system depend mainly on its teachers. If teachers have an established professional identity, it leads to the success of the educational system. Professional identity, like other aspects of the teaching and learning process, is influenced by various factors. Investigating this concept requires identifying the factors affecting it. One of the most important factors that influence teachers' professional identity is teachers' emotions. Teachers' emotions also can have a significant impact on teachers' performance. After searching the databases, this review article examines the role of teachers' emotions and their professional identities in English as a foreign language (EFL) or English as a second language (ESL) classrooms. This review paper unpacks that factors such as teachers' pedagogical beliefs, their positive and negative emotional experiences, their environmental and cultural factors, and their perceptions and expectations of these conditions could affect their emotions as well as their professional identity. Teachers' identity is shaped through ongoing negotiation and interaction that encompasses their personal and professional lives. Taking these factors into account in teacher training courses might notify teachers of the challenges that they might have in their classrooms and provide them with practical solutions.

Although sporadic studies have shown that myoglobin may have better prognostic performance than other cardiac markers in COVID-19, a comprehensive comparative study is lacking. Herein, we retrospectively analyzed the clinical and laboratory data of COVID-19 patients admitted to the Guanggu Campus of Wuhan Tongji Hospital from February 9, 2020 to March 30, 2020, intending to compare the prognostic accuracy of three commonly used cardiac markers on COVID-19 mortality. Our results revealed that abnormal increases in myocardial biomarkers were associated with a significantly increased risk of in-hospital mortality with COVID-19. Interestingly, myoglobin, a non-cardiac-specific biomarker, also expressed in skeletal myocytes, had even higher prognostic accuracy than cardiac-specific biomarkers such as high-sensitivity troponin I (hs-TnI) and creatine kinase-MB (CK-MB). More importantly, multivariate Cox analysis showed that myoglobin, rather than hs-TnI or CK-MB, was independently prognostic for in-hospital mortality in COVID-19. These results were further confirmed by subgroup analyses of patients with severe and critical illnesses and those without a history of cardiovascular disease. Our findings suggest that myoglobin may be a reliable marker of illness reflecting general physiological disturbance and help to assess prognosis and treatment response in patients with COVID-19.

Diabetic kidney disease (DKD) is the major cause of end stage renal disease in patients with type 2 diabetes mellitus (T2DM). The subtle metabolic changes in plasma and cerebrospinal fluid (CSF) might precede the development of DKD by years. In this longitudinal study, CSF and plasma samples were collected from 28 patients with T2DM and 25 controls, during spinal anesthesia for elective surgery in 2017. These samples were analyzed using liquid chromatography-mass spectrometry (LC-MS) in 2017, and the results were correlated with current DKD in 2017, and the development of new-onset DKD, in 2021. Comparing patients with T2DM having new-onset DKD with those without DKD, revealed significantly increased CSF tryptophan and plasma uric acid levels, whereas phosphatidylcholine 36:4 was lower. The altered metabolites in the current DKD cases were uric acid and paraxanthine in the CSF and uric acid, L-acetylcarnitine, bilirubin, and phosphatidylethanolamine 38:4 in the plasma. These metabolic alterations suggest the defective mitochondrial fatty acid oxidation and purine and phospholipid metabolism in patients with DKD. A correlation analysis found CSF uric acid had an independent positive association with the urine albumin-to-creatinine ratio. In conclusion, these identified CSF and plasma biomarkers of DKD in diabetic patients, might be valuable for monitoring the DKD progression.

The district heating area in China is continuously increasing, which brings an increase in district heating load. In order to solve the shortage of heating power and realize the carbon neutral target, this study proposes two retrofit schemes for district heating system by integrating air source heat pump and water source heat pump, respectively. Mathematical models are established to study the performance of the integrated systems and a bilevel optimization model is proposed to optimize them. The results show that the air source heat pump combined district heating system has better performance compared to the conventional system, which reduces 50% energy consumption, 10.8% carbon emissions and achieves better economy. The dynamic coupling property of the district heating network and power grid are also considered, and the results indicate that the introduction of air source heat pump can effectively improve the efficiency and stability of power grid and reduce the seasonal fluctuation. The potential of large-scale application of air source heat pump combined system in Beijing is evaluated. The results reveal that retrofit scheme of integrating air source heat pumps into district heating system can cover 2930 MW heating load and bring 362 million Chinese Yuan profit by reducing 219,000 tons of carbon emissions and 539,000 tons of standard coal consumption in 2025.

The aim of this study was to apply biochemical parameters to Onychostoma barbatulum to understand whether Wuling Farm activities have caused organic pollution from xenoestrogens to flow into surrounding streams and thereby affected area aquatic ecosystems. Individuals of the Taiwan shovel-jaw carp (O. barbatulum) were collected by fyke netting in the Cijiawan, Kaoshan, and Yusheng Rivers in the protected area of Shei-Pa National Park and in the Ikawan River outside the protected areas from 4–5 June 2015 to 20–21 September 2015. The collected male individuals of O. barbatulum were divided into two groups. In the first group monooxygenase (Mon) activity, glutathione S-transferase (GST) activity, and vitellogenin (VTG) concentration in the liver were measured right after they were captured. Those in the second group were acclimated for 14 days and then exposed to 0 (control) or 10 ng/L 17β-estradiol for 10 days and then measured for changes in Mon, GST, and VTG in their livers. The value of VTG concentrations in O. barbatulum individuals collected from the Ikawan River was 2.12 ± 1.62 μg PO42+/g protein, which was the highest among all samples, followed by those collected from the Yusheng River (0.78 ± 1.00 μg PO42+/g protein). Individuals collected from the Yusheng River had the highest liver Mon activity (4.16 ± 1.08△A650/30 min/g protein) and the highest GST activity (1.58 ± 1.13 △A340/20 min/g protein), followed by those from the Ikawan River (Mon: 3.63 ± 1.13 △A650/30 min/g protein; GST: 1.24 ± 0.73 △A340/20 min/g protein). Comprehensive analyses showed that Mon and GST activities and VTG concentrations in livers measured right after being collected were lower than individuals exposed to 10 ng 17β-estradiol/L in the laboratory. Induced VTG concentrations were 9.87 ± 0.89 μg PO42+/g protein, Mon activity 8.02 ± 1.74 △A650/30 min/g protein, and GST activity 3.24 ± 0.62 △A340/20 min/g protein, indicating that farming activities have not significantly affected these aquatic organisms. However, pollution sources are still releasing pollutants containing xenoestrogens into the Yusheng River and Ikawan River. The impact of xenoestrogens is worthy of continuous long-term follow-up monitoring.

Acute respiratory distress syndrome (ARDS) involves dysregulated immune-inflammatory responses, characterized by severe oxidative stress and high mortality. Metabolites modulating the inflammatory and immune responses may play a central role in the pathogenesis of ARDS. Most biogenic amines may induce the production of reactive oxygen species, oxidative stress, mitochondrial dysfunction, and programmed cell death. We conducted a prospective study on metabolic profiling specific to the amino acids and biogenic amines of 69 patients with ARDS. Overall, hospital mortality was 52.2%. Between day 1 and day 7 after ARDS onset, plasma kynurenine levels and the kynurenine/tryptophan ratio were significantly higher among non-survivors than in survivors (all p < 0.05). Urine metabolic profiling revealed a significantly higher prevalence of tryptophan degradation and higher concentrations of metabolites downstream of the kynurenine pathway among non-survivors than among survivors upon ARDS onset. Cox regression models revealed that plasma kynurenine levels and the plasma kynurenine/tryptophan ratio on day 1 were independently associated with hospital mortality. The activation of the kynurenine pathway was associated with mortality in patients with ARDS. Metabolic phenotypes and modulating metabolic perturbations of the kynurenine pathway could perhaps serve as prognostic markers or as a target for therapeutic interventions aimed at reducing oxidative stress and mortality in ARDS.

Bacillus amyloliquefaciens is a probiotic for animals. Evidence suggests that diets supplemented with B. amyloliquefaciens can reduce inflammation; however, the underlying mechanism is unclear and requires further exploration. The exopolysaccharides of B. amyloliquefaciens amy-1 displayed hypoglycemic activity previously, suggesting that they are bioactive molecules. In addition, they counteracted the effect of lipopolysaccharide (LPS) on inducing cellular insulin resistance in exploratory tests. Therefore, this study aimed to explore the anti-inflammatory effect and molecular mechanisms of the exopolysaccharide preparation of amy-1 (EPS). Consequently, EPS reduced the expression of proinflammatory factors, the phagocytic activity and oxidative stress of LPS-stimulated THP-1 cells. In animal tests, EPS effectively ameliorated ear inflammation of mice. These data suggested that EPS possess anti-inflammatory activity. A mechanism study revealed that EPS inhibited the nuclear factor-κB pathway, activated the mitogen-activated protein kinase (MAPK) p38, and prohibited the extracellular signal-regulated kinase 1/2, but had no effect on the c-Jun-N-terminal kinase 2 (JNK). EPS also activated the anti-oxidative nuclear factor erythroid 2–related factor 2 (Nrf2) pathway. Evidence suggested that p38, but not JNK, was involved in activating the Nrf2 pathway. Together, these mechanisms reduced the severity of inflammation. These findings support the proposal that exopolysaccharides may play important roles in the anti-inflammatory functions of probiotics.

Our previous clinical trial showed that a novel concentrated herbal extract formula, YH1 (Rhizoma coptidis and Shen-Ling-Bai-Zhu-San), improved blood glucose and lipid control. This pilot observational study investigated whether YH1 affects microbiota, plasma, and fecal bile acid (BA) compositions in ten untreated male patients with type 2 diabetes (T2D), hyperlipidemia, and a body mass index ≥ 23 kg/m2. Stool and plasma samples were collected for microbiome, BA, and biochemical analyses before and after 4 weeks of YH1 therapy. As previous studies found, the glycated albumin, 2-h postprandial glucose, triglycerides, total cholesterol, and low-density lipoprotein cholesterol levels were significantly improved after YH1 treatment. Gut microbiota revealed an increased abundance of the short-chain fatty acid-producing bacteria Anaerostipes and Escherichia/Shigella. Furthermore, YH1 inhibited specific phylotypes of bile salt hydrolase-expressing bacteria, including Parabacteroides, Bifidobacterium, and Bacteroides caccae. Stool tauro-conjugated BA levels increased after YH1 treatment. Plasma total BAs and 7α-hydroxy-4-cholesten-3-one (C4), a BA synthesis indicator, were elevated. The reduced deconjugation of BAs and increased plasma conjugated BAs, especially tauro-conjugated BAs, led to a decreased glyco- to tauro-conjugated BA ratio and reduced unconjugated secondary BAs. These results suggest that YH1 ameliorates T2D and hyperlipidemia by modulating microbiota constituents that alter fecal and plasma BA compositions and promote liver cholesterol-to-BA conversion and glucose homeostasis.

Enterovirus (EV) 71 caused episodes of outbreaks in China and Southeast Asia during the last few decades. We have previously reported that EV71 induces reactive oxygen species (ROS). However, the underlying mechanism remains elusive. Co-immunoprecipitation-proteomic analysis revealed that enteroviral 2B protein interacted with mitochondrial voltage-dependent anion channel 3 (VDAC3). Knockdown (KD) of VDAC3 expression specifically inhibited enteroviral replication. Single-round viral replication was also inhibited in KD cells, suggesting that VDAC3 plays an essential role in replication. Consistent with this, VDAC3 gene KD significantly reduced the EV71-induced mitochondrial ROS generation. Exogenous 2B expression could induce the mitochondrial ROS generation that was significantly reduced in VDAC3-KD cells or in the Mito-TEMPO-treated cells. Moreover, VDAC3 appears to be necessary for regulation of antioxidant metabolism. VDAC3 gene KD led to the enhancement of such pathways as hypotaurine/taurine synthesis in the infected cells. Taken together, these findings suggest that 2B and VDAC3 interact to enhance mitochondrial ROS generation, which promotes viral replication.

Coenzyme Q10 (CoQ10), a well-known antioxidant, has been explored as a treatment in several neurodegenerative diseases, but its utility in spinocerebellar ataxia type 3 (SCA3) has not been explored. Herein, the protective effect of CoQ10 was examined using a transgenic mouse model of SCA3 onset. These results demonstrated that a diet supplemented with CoQ10 significantly improved murine locomotion, revealed by rotarod and open-field tests, compared with untreated controls. Additionally, a histological analysis showed the stratification of cerebellar layers indistinguishable from that of wild-type littermates. The increased survival of Purkinje cells was reflected by the reduced abundance of TUNEL-positive nuclei and apoptosis markers of activated p53, as well as lower levels of cleaved caspase 3 and cleaved poly-ADP-ribose polymerase. CoQ10 effects were related to the facilitation of the autophagy-mediated clearance of mutant ataxin-3 protein, as evidenced by the increased expression of heat shock protein 27 and autophagic markers p62, Beclin-1 and LC3II. The expression of antioxidant enzymes heme oxygenase 1 (HO-1), glutathione peroxidase 1 (GPx1) and superoxide dismutase 1 (SOD1) and 2 (SOD2), but not of glutathione peroxidase 2 (GPx2), were restored in 84Q SCA3 mice treated with CoQ10 to levels even higher than those measured in wild-type control mice. Furthermore, CoQ10 treatment also prevented skeletal muscle weight loss and muscle atrophy in diseased mice, revealed by significantly increased muscle fiber area and upregulated muscle protein synthesis pathways. In summary, our results demonstrated biochemical and pharmacological bases for the possible use of CoQ10 in SCA3 therapy.