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There are two main challenges in completing surface-enhanced Raman spectroscopy (SERS) detection. One is the small Raman scattering cross-section of methanol, and the other is the derivatization strategy. They were solved by coupling the catalytic strategy with a thermal purge separation and enrichment device. In this study, quantitative analysis of methanol in alcoholic beverages was performed as methanol was catalyzed to formaldehyde. For detecting methanol in low-alcohol beverages, the acetaldehyde derivatives generated by the interaction of ethanol-catalyzed oxide acetaldehyde with 3-methyl 2-benzothiazolinone hydrazone hydrochloride hydrate (MBTH) during the catalytic process will not cause large interference with the SERS signal of formaldehyde. In this case, MBTH with higher sensitivity is selected for the derivatization operation. In the analysis of methanol in high-alcohol beverages, acetylacetonate derivatization without interaction with acetaldehyde was used to avoid the interference of the acetaldehyde generated from ethanol. Based on the detection of formaldehyde in methanol standard solutions, methanol was detected in wine and sake as well as in high-alcohol beverages. Thus, a convenient and rapid method was achieved for the detection of methanol in alcoholic beverages.

The effectiveness and side effects of Type 2 diabetes (T2D) medication are related to individual genetic background. SNPs CYP3A4 and CYP2C19 were introduced to machine-learning models to improve the performance of T2D medication prediction. Two multilabel classification models, ML-KNN and WRank-SVM, trained with clinical data and CYP3A4/ CYP2C19 SNPs were evaluated. Prediction performance was evaluated with Hamming loss, one-error, coverage, ranking loss and average precision. The average precision of ML-KNN and WRank-SVM using clinical data was 92.74% and 92.9%, respectively. Combined with CYP2C19*2*3, the average precision dropped to 88.84% and 89.93%, respectively. While combined with CYP3A4*1G, the average precision was enhanced to 97.96% and 97.82%, respectively. Results suggest that CYP3A4*1G can improve the performance of ML-KNN and WRank-SVM models in predicting T2D medication performance.

Developing efficient and robust catalysts to replace Pt group metals for the oxygen reduction reaction (ORR) is conducive to achieving highly efficient energy conversion.

The coronavirus disease (COVID-19) pandemic has presented challenges in the care of patients with chronic diseases. We identified the challenges faced by Chinese patients with Duchenne muscular dystrophy (DMD) during the pandemic.An online cross-sectional survey was conducted between March 27 and June 30, 2021.Of the 2105 valid questionnaire responses, 2,056 patients were from non-lockdown areas. In these areas, 42.8% reduced outside daily activities, 49.4% reduced rehabilitation service use, 39.7% postponed regular follow-ups, and 40.8% reported accelerated motor function decline. These figures generally increased for patients from lockdown areas-67.3% reduced outside daily activities, 44.9% reduced rehabilitation service use, 79.6% postponed regular follow-ups, and 55.1% reported accelerated motor function decline. Ambulation loss was most commonly reported in September and March before 2020; however, this trend was absent in 2020. Regarding the informed prices of disease-modifying drugs in Europe and the United States, 86.7% could afford a maximum of one-twentieth of the prices, 8.0% could afford one-tenth of the prices, and only 0.6% of the patients could afford the full prices.Implementation of standardized care for DMD in China is consistent with global practices, and the COVID-19 pandemic has affected the care of patients with chronic diseases worldwide, particularly in lockdown areas. Telemedicine is an effective model for providing healthcare to such patients. Healthcare workers should assist patients and establish more robust chronic disease management systems. Collaboration between governmental and non-governmental entities could address the cost of disease-modifying drugs in China and other developing countries.

Cerebral creatine deficiency syndromes (CCDSs) are a group of rare mendelian disorders mainly characterized by intellectual disability, movement anomaly, behavior disorder and seizures. SLC6A8, GAMT, and GATM are known genes responsible for CCDS. In this study, seven pediatric patients with developmental delay were recruited and submitted to a series of clinical evaluation, laboratory testing, and genetic analysis. The clinical manifestations and core biochemical indications of each child were basically consistent with the diagnosis of CCDS. Genetic diagnosis determined that all patients were positive for SLC6A8 or GAMT variation. A total of 12 variants were identified in this cohort, including six novel ones. The frequency of these variants, the Revel scores and the conservatism of the affected amino acids support their pathogenicity. Our findings expanded the mutation spectrum of CCDS disorders, and provided solid evidence for the counseling to affected families.

The metabolism of plasticizing phthalates may correlate with an increased risk of benign prostatic hyperplasia in humans. Diethylphthalate (DEHP) and its metabolites interfere with sex hormone function, causing inflammation and oxidative stress at low doses. The effects may contribute to the development of benign prostate hyperplasia.

Wearable transdermal iontophoresis eliminating the need for external power sources offers advantages for patient-comfort when deploying epidermal diseases treatments. However, current self-powered iontophoresis based on energy harvesters is limited to support efficient therapeutic administration over the long-term operation, owing to the low and inconsistent energy supply. Here we propose a simplified wearable iontophoresis patch with a built-in Mg battery for efficient and controllable transdermal delivery. This system decreases the system complexity and form factors by using viologen-based hydrogels as an integrated drug reservoir and cathode material, eliminating the conventional interface impedance between the electrode and drug reservoir. The redox-active polyelectrolyte hydrogel offers a high energy density of 3.57 mWh cm−2, and an optimal bioelectronic interface with ultra-soft nature and low tissue-interface impedance. The delivery dosage can be readily manipulated by tuning the viologen hydrogel and the iontophoresis stimulation mode. This iontophoresis patch demonstrates an effective treatment of an imiquimod-induced psoriasis mouse. Considering the advantages of being a reliable and efficient energy supply, simplified configuration, and optimal electrical skin-device interface, this battery-powered iontophoresis may provide a new non-invasive treatment for chronic epidermal diseases.

Liver disease is a great danger to human health. The determination of blood level of Cholyglycine acid (CG) is a vital biomarker for the assessment of liver function in clinic, which is contribute to the diagnosis of liver diseases. Thus, establishing accuracy, rapid and convenient method for the detection of glycolic acid is of great significance. In this study, a time-resolved-fluorescence (TRF) lateral flow assay for rapid detection of CG was development. The analytical detection limit (mean of zero-2 SD) was 0.06 μg/mL The method showed good linearity in the range of 0.2–40 g/mL and was not affected by biomolecules with similar structure to CG. The analytical mean recovery of control was between 90–110% and the imprecision of intra- and inter-assay of CVs was less than 10%. No significant matrix effect was observed in saline, serum, plasma or whole blood. A good correlation was found with the homogeneous enzyme immunoassay (HEIA) assay (slopes 1.0463, y-intercepts 0.2721 μg/mL, R = 0.989, n = 50, P < 0.001). The CG TRF analysis could provide reproducible and quantitative information about the state of liver in a few minutes, which is suitable for the detection of liver diseases in point-of-care-testing (POCT) conditions.

The effectiveness and side effects of Type 2 diabetes (T2D) medication are related to individual genetic background. SNPsAbout 10% of adults around the world are living with Type 2 Diabetes (T2D). Due to the huge number of patients and the complexity of individual makeup, it is a challenge for doctors to prescribe appropriate hypoglycemic drugs. To aid prescribing, machine-learning models were developed to predict medication schemes based on patients' demographic information and laboratory test results. These models treat prediction as a multilabel classification problem, with each class of medication as a label. This work was designed to determine whether the introduction of genetic information would improve prediction performance. The machine-learning models were trained using datasets with and without genetic information and their performance was compared. The performance of the machine-learning models was improved by incorporating the SNP

The metabolism of plasticizing phthalates may correlate with an increased risk of benign prostatic hyperplasia in humans. Diethylphthalate (DEHP) and its metabolites interfere with sex hormone function, causing inflammation and oxidative stress at low doses. The effects may contribute to the development of benign prostate hyperplasia.

Background: The purpose of the study was to investigate the levels of amino acids and acylcarnitines in newborns of the Tibet Autonomous Region for the first time and to provide an experimental basis for the diagnosis of genetic metabolic diseases.Methods: We detected concentrations of 43 kinds of amino acids, acylcarnitines and succinylacetone in the dried blood spots of 18482 newborns using liquid chromatography tandem mass spectrometry and diagnose the case by gene sequencing. We compared the indexes between Tibet and our lab, where most data come from an inland area and Han Chinese people. Then we compared amino acid and acylcarnitine levels of seven regions in Tibet and explored their impact factors.Results: We described the levels of amino acids and acylcarnitines in Tibet newborns using 95% confidence intervals. The distribution of amino acid and acylcarnitines were different in Tibet.Conclusion: This study has contributed to filling in the blanks of Tibet newborn screening, which should be considered in the newborn metabolic disease screening in this area.

Based on high-performance liquid chromatography-mass spectrometry (HPLC-MS) and reversed-phase high-performance liquid chromatography-mass spectrometry (RPLC-MS), the changes of drug metabolism and...

Aptamer-based biosensors have been widely constructed and applied to detect diverse targets. Metronidazole is a widely used broad-spectrum antibacterial drug, whose residue has multiple risks to human health. Herein, metronidazole-specific aptamers were selected from a random ssDNA library with the full length of 79 nucleotides (nt) based on DNA library-immobilized magnetic beads SELEX technology. After ten rounds of selection, four aptamers with highly similar secondary structures were selected, among which AP32, with the lowest dissociation constants, was chosen as the optimal aptamer for further optimization. Then a semi-rational post-SELEX truncation was carried out based on the secondary structure analysis and molecular docking, as well as affinity assessment. Redundant nucleotides in AP32 were stepwise removed without the decrease of affinity. Following such strategy, a truncated aptamer AP32-4 with the length of only 15 nt was eventually screened. The dissociation constant of 77.22 ± 11.27 nM is almost equivalent to the original AP32. Furthermore, an aptamer-based fluorescent biosensor for metronidazole was constructed based on AP32-4. With the help of exonuclease-assisted target-recycling amplification, the biosensor exhibits a linear detection range of 25-800 nM, and the detection limit of 10.50 nM. The biosensor was applied to detect metronidazole in honey samples. The results show that not only an efficient strategy for screening robust and practicable aptamers, but also an ultrahigh sensitive detection platform for metronidazole were established.

Background Cobalamin C deficiency (cblC) caused by the MMACHC mutations is the most common type of the disorders of intracellular cobalamin metabolism. While the c.609G > A mutation is most frequent in Chinese cblC patients, its correlation with phenotype has not been delineated. Here we aim to investigate the factors affecting variable phenotypes and outcomes associated with the MMACHC c.609G > A homologous mutation in 149 Chinese cases to have implications for treatment and prevention. Methods We assessed 149 cblC patients caused by MMACHC c.609G > A homozygous mutation. The clinical manifestations, complications, treatment, and outcomes were evaluated; 120 patients were followed-up till December 2019. Results Two patients (1.3%) were prenatally diagnosed, treated after birth and consequently showed normal development. In 15 patients (10.1%) detected by newborn screening, 10 were treated at the age of 2 weeks and showed normal development, while the other 5 were treated after onset and showed neurologic disorders. All 132 clinically diagnosed patients (88.6%) developed symptoms at age from few minutes after birth to 72 months. Among them, 101 (76.5%) had early-onset (before the age of 12 months) and 31 (23.5%) had late-onset (after the age of 12 months). Totally 5 patients died and 24 were lost to follow-up. Of the 132 clinical diagnosed patients, 92 (69.7%) presented with developmental delay, 65 (49.2%) had seizures, 37 (28.0%) had anemia, 24 (18.2%) had feeding difficulty, 23 (17.4%) had ocular problems, and 22 (16.7%) had hydrocephalus. Compared with the non-developmental delay group, the onset age, the age at treatment initiation and the time from onset to treatment initiation were later in the developmental delay group. Seizure group showed significantly higher urinary methylmalonic acid concentration. During long-term follow-up, plasma total homocysteine (tHcy) levels were significantly higher in patients in the uncontrolled group than those in the seizure-free group. Conclusions Most cblC patients caused by MMACHC c.609G > A homozygous mutation showed early-onset. The clinically diagnosed patients usually showed the presence of irreversible brain disorders. Patients treated from the pre-symptomatic stage showed favorable outcomes. Therefore, newborn screening, prenatal diagnosis and early treatment are crucial and the c.609G > A mutant allele should be listed in the pre-pregnancy carrier screening panel in China.

An improved bagging algorithm, combined with a resample strategy, a neural network, and a support vector machine (SVM), is proposed for in-hospital mortality prediction using imbalanced data with very uneven ratio of positive and negative samples. This approach was compared with other machine learning algorithms such as SVM, neural network and GBDT to evaluate its effectiveness. Permutation importance algorithm was employed to assess risk factors for heart failure patients and experimental validation was conducted using medical data from the Chinese PLA General Hospital which consisted of 207 positive and 5975 negative samples, achieving area under curve (AUC), sensitivity, and specificity values of 0.850, 0.800, and 0.752, respectively. The top 5 risk factors extracted are creatinine, serum albumin, lactate dehydrogenase, platelet count, and lymphocytes. These results suggest that the proposed method has the potential to be a valuable new tool for in-hospital mortality prediction using electronic health record data.

Circulating autoantibodies have a close association with autoimmune diseases, which may be seen even in healthy individuals. These are also considered as promising source of new biomarkers in various autoimmune diseases. However, their profile is not completely understood till now. Here, we evaluated autoantibodies against nuclear mitotic apparatus protein located at the carboxy terminus (C-NuMA) in blood circulation of Han Chinese patients, using different technical approaches to discover pathological reaction leading to Behçet’s disease (BD). In the first step, the recombinant human carboxy-terminal region of NuMA peptide (C-NuMA) was over-expressed and purified. In the second step, the indirect immunofluorescence method was used with patients’ sera, and commercial anti-NuMA antibody was used to determine the NuMA as a potential autoantigen. Results were confirmed at cell level by western blots, indicating that two of ten patients with Behçet’s disease could react with the recombinant C-NuMA, and the presence of antibodies were further verified by immunoprecipitation technique. Finally, the corresponding immunoassay (ELISA) was developed and optimized with specific recombinant C-NuMA as an in vitro method to test the confirmed patients with Behçet’s disease. Our findings demonstrated that C-terminus of NuMA is an immune target of Behçet’s disease in Han Chinese patients.

Gestational diabetes mellitus (GDM) is a common clinical disease with complicated clinical process and harmful effects on pregnant women and fetus. The purpose of this study is to use the convenient urine samples in combination with glucose levels to detect or predict GDM. In this study, urine samples of non-pregnant women, normal pregnant women and GDM patients were collected. The peptides in urine were enriched by weak cationic exchange magnetic beads (MB-WCX) and analyzed by matrix assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS). 46 polypeptide peaks with statistical difference (P 0.01) were screened out by using Bioexplorer analysis software. The level of molecules with mass-to-charge ratio of 1079.2, 1290.6 and 1500.7 was higher in the GDM group than the other two groups. Through the analysis of differential molecules by liquid chromatography tandem mass spectrometry (LC-MS), the above molecules were identified as coagulation factor IX, TBC1 family member 5 isoform a [Homo sapiens] (TBC1D5a) and immunoglobulin kappa constant. The discovery of polypeptides provides the research basis for further primary screening and assistant diagnosis of GDM through urine samples.

Introduction Behcet’s disease (BD) is a rare, chronic autoimmune disorder of unknown etiology. Although the profile of autoantibodies for this disease is not yet completely understood, because of better disease recognition, its prevalence is increasing throughout the world. Among ERM proteins (ezrin/radixin/moesin), moesin is a member of a family which is involved in autoimmune diseases. The aim of this study is to confirm whether moesin is a potential anti-endothelial cell autoantigen (AECA) in Hans Chinese BD patients. Material and methods First, a full length recombinant human moesin protein was over-expressed and purified. Second, it was identified by mass spectrometry and then purified moesin was used to perform Western blotting, immunoprecipitation and ELISA with confirmed BD patients. Finally, in vitro cytotoxicity experiments were conducted with anti-moesin antibodies by the resazurin reduction assay method. Results : Purified moesin protein was successfully expressed and then its antigenicity was confirmed by Western blotting and immunoprecipitation techniques. Anti-moesin antibodies were detected in approximately one-third (38%) of BD patients by ELISA and the reactivity of BD serum IgG antibodies against moesin was found to be significantly higher than HC (p < 0.0001). Moreover, in order to validate our results, cytotoxicity experiments also confirmed that anti-moesin antibody had a significant inhibitory effect on endothelial cell activity. Conclusions Expression is correlated with the involvement of moesin as an autoantigen in BD pathology, which is a new finding. It might be a new candidate biomarker in the Han Chinese population.

The reference intervals of biochemical markers were significantly affected by age and gender, especially in minors. In recent years, many provinces and regions in China had established reference intervals for children's hematological indicators. Without considering the instruments and reagents, the reference interval will also be affected by the region, economic development, eating habits, and other factors. Therefore, the reference interval of any hematological indicators is not necessarily a fixed range, it changes with certain factors. In our study, we analyzed the changes of biochemical markers in different serum total Ca and 25-OH-D concentrations, and established the reference intervals of biochemical markers in 3-year-old children, explored the change trend of biochemical markers with different serum total Ca and 25-OH-D concentration.Data was collected from 226 cases of 3-year-old children for biochemical markers, in the Chinese PLA General Hospital in August 2015. The data were divided into a high-level group (serum total Ca2.63 mmol/L and 25-OH-D40.81 ng/mL) and a low-level group (serum total Ca2.54 mmol/L and 25-OH-D32.64 ng/mL) according to serum total Ca and 25-OH-D levels for comparison. The change trend of biochemical markers was compared according to serum total Ca and 25-OH-D level.The Glu levels in boys were significantly higher than that in girls, but CHO and LDL-C in girls were significantly higher than that in boys. The reference intervals of ATL (5.6 - 22.1 U/L), ALB (44.8 - 55.2 g/L), TP (62.7 - 83.1 g/L), ALP (154.4 - 379.7 U/L), GGT (7.2 - 15.9 U/L), Glu (boys: 4.08 - 5.91 mmol/L; girls: 4.05 - 5.37 mmol/L), UREA (2.7 - 6.3 mmol/L), CREA (26.4 - 46.8 µmol/L), UA (182.4 - 400.2 µmol/L), TG (0.43 - 1.67 mmol/L), CHO (boys: 3.19 - 5.96 mmol/L; girls: 3.03 - 6.51 mmol/L), HDL-C (0.98 - 2.24 mmol/L), LDL-C (boys: 1.30 - 3.64 mmol/L; girls: 1.24 - 4.27 mmol/L), total Ca (2.34 - 2.85 mmol/L), PHOS (1.38 - 2.06 mmol/L), Mg (0.83 - 1.06 mmol/L), osteocalcin (41.64 - 91.92 ng/mL), PTH (12.08 - 43.06 pg/mL), 25-OH-D (19.66 - 56.37 ng/mL), β-CrossLaps (0.82 - 1.88 ng/mL), TP1NP (357.9 - 1025.7 μg/L) were established. ALT, TP, ALB, GGT, Glu, CHO, HDL-C, LDL-C, UREA, CREA, PHOS, Mg, and ALP in high level group were significantly higher than those in low level group. There was no significant difference in TG, UA, TP1NP, osteocalcin, PTH and β-CrossLaps between high level group and low-level group. With the increase of serum total Ca and 25-OH-D levels, most of the biochemical markers had a gradually increasing trend. However, biochemical markers of bone (TP1NP, osteocalcin, PTH, β-CrossLaps) showed different trends.This study established the reference intervals of biochemical markers of 3-year-old children. The changes of serum total Ca and 25-OH-D levels in children reflected the changes of glucose and lipid metabolism, liver and kidney function markers, and indirectly reflected the growth and development of children and various organ functions. Maintaining high levels of serum total Ca and 25-OH-D can promote the growth and development of children.

With the development of global economy, the dramatically increased production of polyethylene terephthalate (PET) plastics has led to a remarkably increased amount of plastic waste. PET waste can be treated by landfill, incineration, or biodegradation. While landfilling and incineration may cause secondary pollution, biodegradation has since received increased attentions due to its environmental friendliness. Recent studies have indicated that the carbohydrate binding module (CBM) can effectively enhance the binding of PET degrading enzymes to PET, and consequently increasing PET degradation rate. Here we constructed a fusion protein

Background: The public health emergency has created challenges for the care of patients, particularly those with chronic diseases such as Duchenne muscular dystrophy. To elucidate the challenges faced by Chinese patients with Duchenne muscular dystrophy during the public health emergency coronavirus disease 2019 pandemic, we conducted an online cross-sectional survey, the responses of which were collected between March 27 and June 30, 2021. Results: In total, valid questionnaire responses were obtained from 2,105 patients, of whom 49 lived in pandemic lockdown areas. Of the 2,056 responders from non-lockdown areas, 42.8% reduced their outside daily activities, 49.4% reduced their use of rehabilitation services, 39.7% postponed regular follow-up appointments, and 40.8% complained of accelerated declines in motor function over the previous year. The corresponding figures for the 49 participants from lockdown areas were almost all higher, with 67.3% reducing outside daily activities, 44.9% reducing their use of rehabilitation services, 79.6% postponing regular follow-up appointments, and 55.1% complaining of accelerated declines in motor function. When asked whether they expected more assistance from society than they had received before the pandemic, 60.8% of patients in non-lockdown areas and 87.8% of those in lockdown areas responded affirmatively. When asked whether they felt more anxious than they had before the pandemic and needed psychological counseling, 11.5% of respondents in non-lockdown areas and 18.4% of respondents in lockdown areas responded affirmatively. In non-lockdown areas, 76% of respondents had at least one telemedicine visit, and 71% of them thought that telemedicine was helpful. In lockdown areas, 91.8% had used telemedicine at least once, and 66.7% of them found it helpful.Conclusions: These public health emergency control measures have affected the care of patients with chronic diseases worldwide, particularly pronounced in lockdown areas. It is imperative that healthcare workers assist patients and establish more robust chronic disease management systems. Telemedicine is an effective model for providing healthcare to such patients.

Existing biomarkers for ovarian cancer lack sensitivity and specificity. We compared the diagnostic efficacy of nonlinear machine learning and linear statistical models for diagnosing ovarian cancer using a combination of conventional laboratory indicators. We divided 901 retrospective samples into an ovarian cancer group and a control group, comprising non-ovarian malignant gynecological tumor (NOMGT), benign gynecological disease (BGD), and healthy control subgroups. Cases were randomly assigned to training and internal validation sets. Two linear (logistic regression (LR) and Fisher’s linear discriminant (FLD)) and three nonlinear models (support vector machine (SVM), random forest (RF), and artificial neural network (ANN)) were constructed using 22 conventional laboratory indicators and three demographic characteristics. Model performance was compared. In an independent prospectively recruited validation set, the order of diagnostic efficiency was RF, SVM, ANN, FLD, LR, and carbohydrate antigen 125 (CA125)-only (AUC, accuracy: 0.989, 95.6%; 0.985, 94.4%; 0.974, 93.4%; 0.915, 82.1%; 0.859, 80.1%; and 0.732, 73.0%, respectively). RF maintained satisfactory classification performance for identifying different ovarian cancer stages and for discriminating it from NOMGT-, BGD-, or CA125-positive control. Nonlinear models outperformed linear models, indicating that nonlinear machine learning models can efficiently use conventional laboratory indicators for ovarian cancer diagnosis.

Faecal E. coli can act as reservoirs for resistance genes. Here, we analyzed prevalence of drug resistance in faecal E. coli isolated from healthy children at a single kindergarten in Beijing, China, then used whole genome sequencing to characterize fluoroquinolone-non-susceptible strains. Our results revealed high resistance to ampicillin (54.0%), trimethoprim/sulphurmethoxazole (47.5%) and tetracycline (58.9%) among 576 faecal E. coli isolates, 49.2% of which exhibited multidrug resistance. A total of 113 E. coli isolates were not susceptible to ciprofloxacin, with four sequence types, namely ST1193 (25.7%), ST773 (13.3%), ST648 (8.8%) and ST131 (7.1%) found to be the most prevalent (54.9%). With regards to resistance to quinolones, we detected chromosomal mutations in gyrA, parC, and parE in 111 (98.2%), 105 (92.9%), and 67 (61.1%) isolates, respectively. blaCTX-M (37.2%) was the major ESBL gene, whereas blaCTX-M-14 (12.4%) and blaCTX-M-27 (11.5%) were the most frequent subtypes. A total of 90 (79.6%) ExPEC and 65 (57.5%) UPEC isolates were classified. Overall, these findings revealed clonal spread of certain prevalent STs, namely ST1193, ST773, ST648 and ST131 E. coli isolates in healthy children within a single kindergarten in Beijing, China, affirming the seriousness of the multidrug resistance problem and potential pathogenicity of E. coli isolates in healthy children. Therefore, there is an urgent need for increased surveillance to enhance control of this problem.

Salivary adenoid cystic carcinoma (SACC), one of the most common malignant tumors in the head and neck region, is characterized by high postoperative recurrence rate and poor prognosis. Microwave (MW) ablation possesses advantages in preserving SACC patients' facial aesthetics and oral function, but unfortunately, it suffers from low therapeutic efficacy due to the limited MW-thermal efficiency. Moreover, the insufficient thermal ablation may aggravate hypoxic state in tumors, which is deleterious to the treatment of residual tumors and aggressive tumors. Hence, MW ablation has been rarely applied in treating head and neck tumors in recent years. To minimize the unfavorable outcomes and maximize the therapeutic effects of MW ablation, a MW sensitizer coupled with a self-sufficient oxygen nanoagent was employed for the first time in MW ablation to treat head and neck tumors. We prepared a graphene-containing metal-organic framework (ZIF67@Gr-PEG), which exhibited excellent MW thermal conversion ability endowed by the incorporated Gr and showed

Faecal E. coli can act as reservoirs for resistance genes. Here, we analyzed prevalence of drug resistance in faecal E. coli isolated from healthy children at a single kindergarten in Beijing, China, then used whole genome sequencing to characterize fluoroquinolone-non-susceptible strains. Our results revealed high resistance to ampicillin (54.0%), trimethoprim/sulphurmethoxazole (47.5%) and tetracycline (58.9%) among 576 faecal E. coli isolates, 49.2% of which exhibited multidrug resistance. A total of 113 E. coli isolates were not susceptible to ciprofloxacin, with four sequence types, namely ST1193 (25.7%), ST773 (13.3%), ST648 (8.8%) and ST131 (7.1%) found to be the most prevalent (54.9%). With regards to resistance to quinolones, we detected chromosomal mutations in gyrA, parC, and parE in 111 (98.2%), 105 (92.9%), and 67 (61.1%) isolates, respectively. bla CTX-M (37.2%) was the major ESBL gene, whereas bla CTX-M-14 (12.4%) and bla CTX-M-27 (11.5%) were the most frequent subtypes. A total of 90 (79.6%) ExPEC and 65 (57.5%) UPEC isolates were classified. Overall, these findings revealed clonal spread of certain prevalent STs, namely ST1193, ST773, ST648 and ST131 E. coli isolates in healthy children within a single kindergarten in Beijing, China, affirming the seriousness of the multidrug resistance problem and potential pathogenicity of E. coli isolates in healthy children. Therefore, there is an urgent need for increased surveillance to enhance control of this problem.

Introduction: The major clinical problem presently confronting the Chinese newborn screening (NBS) programs by tandem mass spectrometry (MS/MS) is the lack of comprehensive reference intervals (RIs) for disease biomarkers. To close this gap, the Chinese National Center for Clinical Laboratories (NCCL) launched a nationwide study to investigate the dynamic pattern of 35 MS/MS NBS biomarkers and establish accurate and robust RIs.Methods: Blood spot samples from 4,714,089 Chinese neonates were tested in participating centers/laboratories and used for study analysis. MS/MS NBS biomarker trends were visually assessed by their concentrations over age. Specific partitions were determined arbitrarily by each day and sex or by the statistical method of Harris and Boyd. RIs, corresponding to the 2.5th and 97.5th percentiles, as well as the 1th, 25th, 75th and 99th percentiles were calculated for each reference partition using a non-parametric rank approach.Results: Most MS/MS NBS biomarkers fluctuated during the first week of life, followed by a relatively stable concentration. Age and sex-specific RIs were established and presented an improved specificity over the RIs used in participating centers/laboratories. Females demonstrated higher 2.5th and 97.5th percentiles in all amino acids except arginine and ornithine than males, whereas males showed higher 2.5th and 97.5th percentiles in most acylcarnitines.Conclusion: The present study determined the dynamic trends of 35 MS/MS biomarkers and established age and sex-specific RIs, valuably contributing to the current literature and timely evaluation of neonatal health and disease.

Dextranase has extensive applications in the food, pharmaceutical, and chemical industries. However, enzyme production by the wild-type strain is generally low and few studies have conducted structural analysis of dextranase. This study describes an efficient and stable mutagenesis method for producing dextranase and the relationship between the enzyme structure and enzymatic properties before and after mutagenesis. Wild-type Chaetomium globosum was mutated by combined atmospheric and room temperature plasma treatment and ethyl methyl sulfone application. Mutant strains were screened for optimal dextranase production ability and genetic stability. The maximum yield of dextranase reached 824.73 U/mL. Dextranase produced by the mutant strain displayed the same optimum pH and temperature values of 5.5 and 60℃, respectively, as dextranase produced by the wild-type strain. However, dextranase from the mutant strain showed greater heat stability at 70℃. Furthermore, the three-dimensional structure of the enzyme changed slightly after mutagenesis, with the amino acid residue at position 578 changing from His to Leu. This change in the three-dimensional structure affected the properties of dextranase. Finally, dextranase significantly inhibited the growth of Streptococcus mutans. The results indicated dextranase from Chaetomium globosum would give potential implications in the medical, prevent dental caries and food industries.

Fructus Sophorae (FS), the dry mature fruit of Sophora japonica Leguminosae, is a valuable traditional Chinese medicine resource with flavonoids as the major active ingredients. To identify the plant-derived estrogen-like flavonoids serving as potential osteoporosis chemopreventive agents, we isolated and identified 27 flavonoids compounds, including 17 compounds obtained for the first time from FS. To screen out the flavonoids with estrogen-like biological behavior from the 11 high yield compounds, we set up an in vitro screening system in rat osteoblast MC3T3-E1 cells including MTT assay, alkaline phosphatase staining and Alizarin red S staining assay to examine the effects on cell proliferation, differentiation and mineralization of osteoblast cells respectively. Six flavonoids, including genistein, sophoricoside, sophorabioside, sophoraflavonoloside, nicotiflorin and rutin, significantly increased the cellular activity of MC3T3-E1 cells. Furthermore, blocking the estrogen receptor signaling by tamoxifen compromised the effects above significantly, suggesting the 6 compounds behave as estrogen-like reagents. Moreover, the interaction between the six flavonoids from FS and estrogen receptor was clarified by molecular docking method from Glide XP. Collectively, being used as food and medicine in China, FS is rich in flavonoids with estrogen-like effects, may be used as healthy supplementary in treating postmenopausal women osteoporosis.

Directed hydrolysis of corn crude peptides was performed by sequential digestion with α-chymotrypsin and carboxypeptidase A. With the additional step of adsorption of aromatic amino acids by activated carbon, corn oligopeptides with a Fischer’s ratio of 41.87 and low bitterness were prepared. The fraction with molecular weight of 180–1000 Da was found to constitute 71.37% of these oligopeptides, where the proportion of Phe and Tyr among all amino acid residues was only 0.73%. In addition, a model of liver injury induced by carbon tetrachloride was established. Through the analysis of the body–mass index, liver index, liver histopathological features, and various serum biochemical indicators of liver function, high Fischer’s ratio corn oligopeptides were found to be safe and slightly superior in terms of liver injury repair when compared with a commercial high Fischer’s ratio amino acid product. Crude corn peptides (raw material) and skimmed milk powder had no effect on repairing liver injury.

Renal dysfunction, which is associated with bad clinical outcomes, is one of the most common complications of heart failure (HF). Timely prediction of renal dysfunction can help medical staffs intervene early to avoid catastrophic consequences. In this paper, we proposed a multi-task deep and wide neural network (MT-DWNN) for predicting fatal complications during hospitalization. The algorithm was tested on a dataset collected from Chinese PLA General Hospital, which contains 35,101 hospitalizations with HF diagnosis during the last 18 years, and 2,478 hospitalizations with a diagnosis of renal dysfunction. For the renal dysfunction task, the AUC of the proposed method is 0.9393, which is a significant improvement ($p

The construction of the hierarchical nanostructures of inorganic materials with high stability has attracted great attention for photothermal therapy. In this paper, we presented the preparation of urchin-like LaWO4Cl nanostructures assembled with nanoribbons via a facile solvothermal reaction. X-ray diffraction (XRD) analysis confirmed the formation of good crystalline urchin-like LaWO4Cl assemblies. Energy dispersive X-ray spectroscopy (EDX) and X-ray photoelectron spectroscopy (XPS) revealed the element composition of the prepared urchin-like nanostructures. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) investigations showed that the urchin-like LaWO4Cl assemblies were composed of single crystalline nanoribbons with diameters less than 10 nm. When excited with an 808 nm near-infrared (NIR) laser at the power density of 1.91 W cm-2 for 5 min, the temperature quickly increased to 52 °C. The in vitro cytotoxicity of urchin-like LaWO4Cl was tested with human cervical cancer cells (HeLa), revealing excellent biocompatibility. More importantly, the photothermal treatment with urchin-like LaWO4Cl displayed great therapeutic efficacy in vitro. Thus, urchin-like LaWO4Cl would be a new promising NIR light-driven photothermal agent, which can also pave a new way for the material design of PTT agents.

Background: Nucleic acid detection and CT scanning have been reported in COVID-19 diagnosis. Here, we aimed to investigate the clinical significance of IgM and IgG testing for the diagnosis of highly suspected COVID-19.Methods: A total of 63 patients with suspected COVID-19 were observed, 57 of whom were enrolled (24 males and 33 females). The selection was based on the diagnosis and treatment protocol for COVID-19 (trial Sixth Edition) released by the National Health Commission of the People's Republic of China. Patients were divided into positive and negative groups according to the first nucleic acid results from pharyngeal swab tests. Routine blood tests were detected on the second day after each patient was hospitalized. The remaining serum samples were used for detection of novel coronavirus-specific IgM/IgG antibodies.Results: The rate of COVID-19 nucleic acid positivity was 42.10%. The positive detection rates with a combination of IgM and IgG testing for patients with COVID-19 negative and positive nucleic acid test results were 72.73 and 87.50%, respectively.Conclusions: We report a rapid, simple, and accurate detection method for patients with suspected COVID-19 and for on-site screening for close contacts within the population. IgM and IgG antibody detection can identify COVID-19 after a negative nucleic acid test. Diagnostic accuracy of COVID-19 might be improved by nucleic acid testing in patients with a history of epidemic disease or with clinical symptoms, as well as CT scans when necessary, and serum-specific IgM and IgG antibody testing after the window period.

Background The purpose of this study was to analyze the coagulation status of gestational diabetes mellitus (GDM) patients in combination with glucose levels and screen out indicators closely related to the severity of GDM and adverse pregnancy outcome. Methods The subjects of 110 GDM patients and 100 normal pregnant women were randomly selected. The results of prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (FIB), D-dimer (D-D), and plaque level test (PLT) in GDM patients and normal pregnant women (comparison group) were analyzed. The study screened out the coagulation indexes of GDM closely related to FPG and then analyzed the correlation between indexes and adverse prognosis. Results The results of PT were significantly lower in the GDM group. The PT was related to the severity of GDM and adverse pregnancy outcome. Conclusions The PT levels of GDM patients in the third trimester can be used as a reliable index for disease and prognosis evaluation.

Efficient data sharing schemes are one of the key technologies in the Internet of Vehicles (IoV). However, the insufficient willingness of vehicle users to provide data makes the traditional blockchain-based IoV network have low throughput. The income of IoV providers decreases when the vehicle density increases on the road. In this paper, we investigated a mobile vehicle data sharing scheme based on the consortium blockchain. In detail, the consortium blockchain was used to limit the degree of decentralization and openness, and the optimal revenue strategy approach between vehicles and data-demand devices was obtained through the Stackelberg game. The load test library based on Node.js was used to simulate and compare the data transmission performance of the proposed consortium blockchain with traditional blockchain schemes. Simulation results show that the proposed scheme had higher buyer’s revenue, and the block transmission performance was significantly higher than that of traditional blockchain schemes.

To solve the memory losses of raw information due to the deepening network layers, a model based on memory correction mechanism is adopted to address the attention bias and the raw information losses. By introducing memory correction mechanism to GA Reader, option coding module is applied to RACE dataset for solving the issue that datasets have fewer demands for deep reasoning ability and contain noises. According to the experiment and analysis, the optimized model has each layer fused with the raw document information in the process of network iterative learning to keep correcting attention for the iterating network. Meanwhile, the reasoning ability needed for the model has also been improved. The RACE machine selection reading comprehension model based on memory correction could effectively solve the issue of raw information losses and overly simplified datasets.

Hepatocellular carcinoma (HCC) is a severe global health problem. There is increasing evidence for the important roles of long noncoding RNAs in tumorigenesis and metastasis in HCC. In this study, we identified and characterized a novel long noncoding RNA, LINC02580, involved in HCC. LINC02580 was highly downregulated in HCC cohorts and was identified as a tumor suppressor. Low LINC02580 expression in patients with HCC was correlated with poor prognosis. Functional assays indicated that LINC02580-deficient cells show enhanced colony formation, migration, and invasion in vitro and promote subcutaneous tumor formation and distant lung metastasis in vivo. With respect to the underlying mechanism, we found that LINC02580 modulates the epithelial–mesenchymal transition (EMT) associated pathway in HCC cells by specifically binding to serine and arginine-rich splicing factor 1 (SRSF1). In summary, our findings illustrated that LINC02580 is a metastasis-suppressing lncRNA in HCC, and provided vital clues of how LINC02580 performs its biological functions. Further, this lncRNA may be a potential target in the prognosis and treatment of HCC.

COVID-19 is caused by SARS-CoV-2 infection and was initially discovered in Wuhan. This outbreak quickly spread all over China and then to more than 20 other countries. SARS-CoV-2 fluorescent microsphere immunochromatographic test strips were prepared by the combination of time-resolved fluorescence immunoassay with a lateral flow assay. The analytical performance and clinical evaluation of this testing method was done and the clinical significance of the testing method was verified. The LLOD of SARS-CoV-2 antibody IgG and IgM was 0.121U/L and 0.366U/L. The specificity of IgM and IgG strips in healthy people and in patients with non-COVID-19 disease was 94%, 96.72% and 95.50%, 99.49%, respectively; and sensitivity of IgM and IgG strips for patients during treatment and follow-up was 63.02%, 37.61% and 87.28%, 90.17%, respectively. The SARS-CoV-2 antibody test strip can provide rapid, flexible and accurate testing, and is able to meet the clinical requirement for rapid on-site testing of virus. The ability to detect IgM and IgG provided a significant benefit for the detection and prediction of clinical course with COVID-19 patients.

A novel electrochemical aptasensor for ATP was developed based on an aptamer-embedded configuration-switchable tetrahedral DNA nanostructure (TDN) and the formation of a G-quadruplex. This unique TDN was formed through the self-assembly of four specially designed single-stranded DNA (ssDNA) sequences (S1, S2, S3 and S4). The TDN was immobilized on the surface of a Au electrode through the thiol groups at the 5′-end of S1, S2 and S3. Five edges of the TDN were designed to form a double helix to preserve the structural robustness of the tetrahedron, while the ATP aptamer embedded sequence (S3) was designed to be located at the rest edge. The two terminals of S4 at the same edge were composed of two split G-quadruplex-forming sequences, which were non-complementary to the aptamer. This edge offered the configuration-switchable characteristic of the TDN. In the absence of ATP, the TDN remained in a relaxed state, and the G-quadruplex cannot form due to the large distance between the split G-quadruplex-forming sequences. However, in the presence of ATP, the aptamer combined with ATP and shortened the distance between the split sequences, resulting in the taut state of the TDN and the formation of a G-quadruplex at the edge. After the addition of hemin, the differential pulse voltammograms (DPVs) were used to quantify ATP. The sensor revealed a dynamic response range from 0.1 nM to 1 μM, with a detection limit of 50 pM. In addition, the specificity and practicability in real samples were also verified, indicating its potential applications.

BACKGROUND Although mutations and dysfunction of mitochondrial DNA (mtDNA) are related to a variety of diseases, few studies have focused on the relationship between mtDNA and coronary artery disease (CAD), especially the relationship between rare variants and CAD. MATERIAL AND METHODS Two-stage high-throughput sequencing was performed to detect mtDNA variants or heteroplasmy and the relationship between them and CAD phenotypes. In the discovery stage, mtDNA was analyzed by high-throughput sequencing of long-range PCR products generated from the peripheral blood of 85 CAD patients and 80 demographically matched controls. In the validation stage, high-throughput sequencing for mtDNA target regions captured by GenCap Kit was performed on 100 CAD samples and 100 controls. Finally, tRNA fine mapping was performed between our study and the reported Chinese CAD study. RESULTS Among the tRNA genes, we confirmed a highly conserved rare variant, A5592G, previously reported in the Chinese CAD study, and 2 novel rare mutations that reached Bonferroni's correction significance in the combined analysis were found (P=7.39×10-4 for T5628C in tRNAAla and P=1.01×10-5 for T681C in 12S rRNA) in the CAD study. Both of them were predicted to be pathological, with T5628C disrupting an extremely conservative base-pairing at the AC stem of tRNAAla. Furthermore, we confirmed the controversial issue that the number of non-synonymous heteroplasmic sites per sample was significantly higher in CAD patients. CONCLUSIONS In conclusion, our study confirmed the contribution of rare variants in CAD and showed that CAD patients had more non-synonymous heterogeneity mutations, which may be helpful in identifying the genetic and molecular basis of CAD.

Gestational diabetes mellitus (GDM) is a common disease of pregnant women, which has a higher incidence in recent years. The purpose of this study is to explore urinary biomarkers that could predict and monitor gestational diabetes mellitus (GDM). Urine samples from 30 normal pregnant women and 78 GDM patients were collected and purified by weak cationic exchange magnetic beads (MB-WCX), then analyzed by matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS). The urinary peptide signatures of the two groups were compared by BioExplorer software. The potential ability of the differently expressed peptides to distinguish GDM patients from normal pregnant women was evaluated by receiver operating characteristic (ROC) analysis. At last, the differently expressed peptides were identified by liquid chromatography tandem mass spectrometry (LC-MS). There were four differently expressed peptides (m/z 1000.5, 1117.5, 1142.9, and 2022.9) between two groups, which were identified as fragments of urinary albumin, α2-macroglobulin, human hemopexin, and α1-microglobulin, respectively. The diagnostic efficacy of m/z 1142.9 was better than the other peptides. The area under the curve (AUC) of the m/z 1142.9 was 0.690 (95% CI: 0.583-0.796). The discovery of urinary polypeptides provides the possibility for the early prediction of GDM and the monitoring of glucose metabolism in GDM patients by a noninvasive method.

A fluorescent aptasensor for Staphylococcus aureus (S. aureus) is designed, which takes advantage of strand displacement amplification (SDA) technology and unique self-assembled DNA hexagonal structure. In the presence of S. aureus, a partially complementary strand of S. aureus aptamer (cDNA) is competitively released from cDNA/aptamer duplex immobilized on magnetic beads due to the affinity of the aptamer for S. aureus. The addition of primer starts the SDA reaction. With the catalysis of Bsm DNA polymerase and Nb.bpu10I endonuclease, a large number of single-stranded DNA (ssDNA) is produced, which induces the opening of a hairpin probe and the subsequent self-assembly to form a hexagonal structure. The staining of the DNA hexagon with SYBR Green I excites the fluorescence signal, which is used for detection. The aptasensor exhibits a broad linear range from 7 to 7 × 107 CFU/mL, with a detection limit of 1.7 CFU/mL for S. aureus. The sensor shows negligible responses to other bacteria. Moreover, the aptasensor has been applied to detect S. aureus in milk samples, and the results demonstrate the general applicability of the sensor and its prospect in systematic detection of S. aureus in food safety control and medicine-related fields.

Quick, simple and accurate diagnosis of suspected COVID-19 is very important for the screening and therapy of patients. Although several methods were performed in clinical practice, however, the IgM and IgG diagnostic value evaluation was little performed. 57 suspected COVID-19 infection patients were enrolled in our study. 24 patients with positive and 33 patients with negative nucleic acid test. The positive rate of COVID-19 nucleic acid was 42.10%. The positive detection rate of combination of IgM and IgG for patients with COVID-19 negative and positive nucleic acid test was 72.73% and 87.50%. The results were significantly higher than the nucleic acid or IgM, IgG single detection. hsCRP in the COVID-19 nucleic acid negative group showed significantly higher than the positive groups (P=0.0298). AST in the COVID-19 IgM negative group showed significantly lower than the positive groups (P=0.0365). We provided a quick, simple, accurate aided detection method for the suspected patients and on-site screening in close contact with the population.