CDBN-YGXZ, a Novel Small-Molecule Drug, Shows Efficacy against Clostridioides difficile Infection and Recurrence in Mouse and Hamster Infection Models.

Clostridioides difficile infection (CDI) causes severe diarrhea and colitis, leading to significant morbidity, mortality, and high medical costs worldwide. Oral vancomycin, a first-line treatment for CDI, is associated with a high risk of recurrence, necessitating novel therapies for primary and recurrent CDI. A novel small-molecule compound, CDBN-YGXZ, was synthesized by modifying the benzene ring of nitazoxanide with lauric acid. The mechanism of action of CDBN-YGXZ was validated using a pyruvate:ferredoxin/flavodoxin oxidoreductase (PFOR) inhibition assay. The efficacy of CDBN-YGXZ was evaluated using the MIC test and CDI infection model in mice and hamsters. Furthermore, metagenomics was used to reveal the underlying reasons for the effective reduction or prevention of CDI after CDBN-YGXZ treatment. The inhibitory activity against PFOR induced by CDBN-YGXZ. MIC tests showed that the in vitro activity of CDBN-YGXZ against C. difficile ranging from 0.1 to 1.5 µg/mL. In the mouse and hamster CDI models, CDBN-YGXZ provided protection during both treatment and relapse, while vancomycin treatment resulted in severe relapse and significant clinical scores. Compared with global effects on the indigenous gut microbiota induced by vancomycin, CDBN-YGXZ treatment had a mild influence on gut microbes, thus resulting in the disappearance or reduction of CDI recurrence. CDBN-YGXZ displayed potent activity against C. difficile in vitro and in vivo, reducing or preventing relapse in infected animals, which could merit further development as a potential drug candidate for treating CDI.

A pilot study of cdc6 as a biomarker for circulating tumor cells in patients with lung cancer.

BACKGROUND: Cell division cycle 6 (cdc6) is a key factor of DNA replication initiation license system and a proto-oncogene. It has been detected in some tumor tissues to aid cancer diagnosis in many research projects. However, it remains unclear that if cdc6 could be detected in the peripheral blood, just like liquid biopsy, in solid tumor patients. The aim of this study is to investigate the possibility of cdc6 as a biomarker for circulating tumor cells in patients with lung cancer. METHODS: We first detected the expression of cdc6 in peripheral blood mononuclear cells (PBMCs) and tumor cells by in situ hybridization with cdc6 RNA probe. Then, we examined the expression of cdc6 in PBMCs from health individual, mononuclear cells from cord blood, or A549 cell line by RT-qPCR. Furthermore, we used RT-qPCR to test the cdc6 expression in PBMCs from tumor patients (test group) and non-tumor individuals as a control group. Chi-square test with Fisher's exact test was used to analyze the statistical significance of the difference. P < .05 is considered as statistically significant difference. RESULTS: When compared the cdc6 expression in cells from difference sources, we found that A549 tumor cell line had the strongest expression of cdc6, samples from cord blood showed the least expression level, indicating the detection strategy of RT-qPCR is reasonable. Using this method, we studied whether cdc6 in Peripheral blood could be detected as a biomarker by examining cdc6 expression from PBMCs of patients with lung cancer. We found 20% of patients with lung cancer were cdc6 positive in PBMCs, whereas only 4.26% was found positive in the control group (P = .039, P < .05). CONCLUSION: Cell division cycle 6 has a potential to be used as a circulating tumor cell biomarker for lung cancer. Further study in clinical application is still broad needed.

Chromosome-scale genome assembly of Lepus oiostolus (Lepus, Leporidae).

Lepus oiostolus (L. oiostolus) is a species endemic to the Qinghai-Tibet Plateau. However, the absence of a reference genome limits genetic studies. Here, we reported a high-quality L. oiostolus genome assembly, with scaffolds anchored to 24 chromosomes and a total assembled length of 2.80 Gb (contig N50 = 64.25 Mb). Genomic annotation uncovered 22,295 protein-coding genes and identified 49.84% of the sequences as transposable elements. Long interspersed nuclear elements (LINEs) constitute a high proportion of the genome. Our study is at the first time to report the chromosome-scale genome for the species of the L. oiostolus. It provides a valuable genomic resource for future research on the evolution of the Leporidae.

[Analysis of the chloroplast genome of Incarvillea younghusbandii Sprague].

Incarvillea younghusbandii Sprague is a traditional tonic herb. The roots are used as herbal medicine for nourishing and strengthening, as well as treating postpartum milk deficiency and weakness. In this study, the chloroplast genome of I. younghusbandii was sequenced and assembled by the high-throughput sequencing technology. The sequence characteristics, sequence repeats, codon usage bias, phylogenetic relationships and estimated divergence time of I. younghusbandii were analyzed. The 159 323 bp sequence contained a large single copy (80 197 bp), a small single copy (9 030 bp) and two inverted repeat sequences (35 048 bp). It contained 120 genes, including 77 protein coding genes, 8 ribosomal RNA genes and 35 transfer RNA genes. AAA was the most frequent codon in the chloroplast coding sequence of I. younghusbandii. A total of 42 simple sequence repeats were identified in the chloroplast genome. Phylogenetic analysis revealed I. younghusbandii was mostly like its taxonomically close relative Incarvillea compacta. The divergence between I. younghusbandii and I. compacta was dated to 4.66 million years ago. This study was significant for the scientific conservation and development of resources related to I. compacta. It also provides a basic genetic resource for the subsequent species identification of the genus Incarvillea, and the population genetic diversity study of Bignoniaceae.

Magnetic Resonance Perfusion-Weighted Imaging in Predicting Hemorrhagic Transformation of Acute Ischemic Stroke: A Retrospective Study.

Hemorrhagic transformation (HT) is one of the common complications in patients with acute ischemic stroke (AIS). This study aims to investigate the value of different thresholds of Tmax generated from perfusion-weighted MR imaging (PWI) and the apparent diffusion coefficient (ADC) value in the prediction of HT in AIS. A total of 156 AIS patients were enrolled in this study, with 55 patients in the HT group and 101 patients in non-HT group. The clinical baseline data and multi-parametric MRI findings were compared between HT and non-HT groups to identify indicators related to HT. The optimal parameters for predicting HT and the corresponding cutoff values were obtained using the receiver operating characteristic curve analysis of the volumes of ADC < 620 × 10-6 mm2/s and Tmax > 6 s, 8 s, and 10 s. The results showed that the volumes of ADC < 620 × 10-6 mm2/s and Tmax > 6 s, 8 s, and 10 s in the HT group were all significantly larger than that in the non-HT group and were all independent risk factors for HT. Early measurement of the volume of Tmax > 10 s had the highest value, with a cutoff lesion volume of 10.5 mL.

Change of water consumption and its potential influential factors in Shanghai: a cross-sectional study.

BACKGROUND: Different water choices affect access to drinking water with different quality. Previous studies suggested social-economic status may affect the choice of domestic drinking water. The aim of this study is to investigate whether recent social economic changes in China affect residents' drinking water choices. METHODS: We conducted a cross-sectional survey to investigate residents' water consumption behaviour in 2011. Gender, age, education, personal income, housing condition, risk perception and personal preference of a certain type of water were selected as potential influential factors. Univariate and backward stepwise logistic regression analyses were performed to analyse the relation between these factors and different drinking water choices. Basic information was compared with that of a historical survey in the same place in 2001. Self-reported drinking-water-related diarrhoea was found correlated with different water choices and water hygiene treatment using chi-square test. RESULTS: The percentage of tap water consumption remained relatively stable and a preferred choice, with 58.99% in 2001 and 58.25% in 2011. The percentage of bottled/barrelled water consumption was 36.86% in 2001 and decreased to 25.75% in 2011. That of household filtrated water was 4.15% in 2001 and increased to 16.00% in 2011. Logistic regression model showed strong correlation between one's health belief and drinking water choices (P < 0.001). Age, personal income, education, housing condition, risk perception also played important roles (P < 0.05) in the models. Drinking-water-related diarrhoea was found in all types of water and improper water hygiene behaviours still existed among residents. CONCLUSIONS: Personal health belief, housing condition, age, personal income, education, taste and if worm ever founded in tap water affected domestic drinking water choices in Shanghai.

Deep Learning for Clothing Style Recognition Using YOLOv5.

With the rapid development of artificial intelligence, much more attention has been paid to deep learning. However, as the complexity of learning algorithms increases, the needs of computation power of hardware facilities become more crucial. Instead of the focus being on computing devices like GPU computers, a lightweight learning algorithm could be the answer for this problem. Cross-domain applications of deep learning have attracted great interest amongst researchers in academia and industries. For beginners who do not have enough support with software and hardware, an open-source development environment is very helpful. In this paper, a relatively lightweight algorithm YOLOv5s is addressed, and the Google Colab is used for model training and testing. Based on the developed environment, many state-of-art learning algorithms can be studied for performance comparisons. To highlight the benefits of one-stage object detection algorithms, the recognition of clothing styles is investigated. The image samples are selected from datasets of fashion clothes and the web crawling of online stores. The image data are categorized into five groups: plaid; plain; block; horizontal; and vertical. Average precison, mean average precison, recall, F1-score, model size, and frame per second are the metrics used for performance validations. From the experimental outcomes, it shows that YOLOv5s is better than other learning algorithms in the recognition accuracy and detection speed.

The construction of an improved model of acute subdural hematoma in rats.

BACKGROUND: To construct a new and improved model of acute subdural hematoma in rats. NEW METHOD: 30 male adult Sprague-Dawley rats(SD rats) were selected and randomly divided into two groups. The traditional model group was based on Miller's model construction method, and the improved model group was based on improved needle, injection site and operation method. The improved model was evaluated by comparing the physiological indicators, behavioral scores, magnetic resonance performance and HE staining results of the two groups of rats. RESULTS: The physical signs of the rats in the two groups were similar. The survival rate of the improved group was higher than that of the traditional group. The hematoma in the improved model was thicker and concentrated in the ipsilateral side, as revealed by HE staining and MRI. The improved method has less intrusions on the cortex around the injection site and is more stable than the traditional model. COMPARISON WITH EXISTING METHOD(S): The operation difficulty of the improved model is reduced and easier. The survival rate of the improved group was higher than that of the traditional group. And the improved model will have more research possibilities. CONCLUSION: The improved model is based on the traditional model. Although it has some shortcomings, it can also be used in different research fields of the traditional model. The operation for the improved model is easier to perform. And the improved model has more applications in research.

HSP60 Regulates Lipid Metabolism in Human Ovarian Cancer.

Accumulating evidence demonstrates that cancer is an oxidative stress-related disease, and oxidative stress is closely linked with heat shock proteins (HSPs). Lipid oxidative stress is derived from lipid metabolism dysregulation that is closely associated with the development and progression of malignancies. This study sought to investigate regulatory roles of HSPs in fatty acid metabolism abnormality in ovarian cancer. Pathway network analysis of 5115 mitochondrial expressed proteins in ovarian cancer revealed various lipid metabolism pathway alterations, including fatty acid degradation, fatty acid metabolism, butanoate metabolism, and propanoate metabolism. HSP60 regulated the expressions of lipid metabolism proteins in these lipid metabolism pathways, including ADH5, ECHS1, EHHADH, HIBCH, SREBP1, ACC1, and ALDH2. Further, interfering HSP60 expression inhibited migration, proliferation, and cell cycle and induced apoptosis of ovarian cancer cells in vitro. In addition, mitochondrial phosphoproteomics and immunoprecipitation-western blot experiments identified and confirmed that phosphorylation occurred at residue Ser70 in protein HSP60, which might regulate protein folding of ALDH2 and ACADS in ovarian cancers. These findings clearly demonstrated that lipid metabolism abnormality occurred in oxidative stress-related ovarian cancer and that HSP60 and its phosphorylation might regulate this lipid metabolism abnormality in ovarian cancer. It opens a novel vision in the lipid metabolism reprogramming in human ovarian cancer.

[Determination of trace iodide in drinking water in Shanghai by two columns and gas chromatography with electron capture detection].

OBJECTIVE: To modify and optimize gas chromatographic conditions, qualitative and quantitative method on the base of the actual national standard detection method for drinking water on testing iodide with gas chromatography, and detect iodide in drinking water of Shanghai. METHODS: Iodobutane derivative was identified by gas chromatography/mass spectrometry, then two capillary columns coupled to electron capture detector were made by qualitative and quantitative analysis. Finally, 100 ml water samples were collected respectively from raw water and finished water of three plants in which water sources were Yangtse river, Huangpu river, and inner river respectively and detected by this developed method. RESULTS: The results of mass spectrometry showed that iodide would form iodobutane which could generate 1-iodo-2-butanone and 3-iodo-2-butanone isomers by derivatization. The data of qualitative analysis by two capillary columns revealed that iodobutane was separated completely and the total time of chromatogram separation was 19.33 min.3-iodo-2-butanone with the high response value was selected to quantitatively analyse. The linear range was 1 - 100 µg/L, and the coefficient of determination (r(2)) was 0.9997. The limit of detection was 13 ng/L. Recoveries were between 97.68% and 104.37%, and relative standard deviations were between 2.14% and 4.41%. The results of iodide detected by this method in raw water and finished water in three plants in Shanghai showed that the ranking of iodide's concentration in raw water was Huangpu river (15.14 µg/L) > inner river (6.97 µg/L) > Yangtse river (3.55 µg/L). The level of iodide in finished water of plant 1 (3.55 µg/L and 5.92 µg/L for raw and finished water respectively) and 3 (6.97 µg/L and 9.62 µg/L for raw and finished water respectively) increased slightly except for plant 2 (15.14 µg/L and 1.81 µg/L for raw and finished water respectively). The relative standard deviations of all water samples measured in duplicate were less than 9.73%. CONCLUSION: The improved method possesses higher degree of sensitivity and accuracy of qualitative and quantitative analysis than actual national standard detection method, and it is fit for trace analysis of iodide in water.

Photothermal Fenton Nanocatalysts for Synergetic Cancer Therapy in the Second Near-Infrared Window.

Chemodynamic therapy (CDT) that utilizes endogenous hydrogen peroxide (H2O2) to produce reactive oxygen species (ROS) to kill cancer cells has shown a promising strategy for malignant tumor treatment. Nevertheless, limited H2O2 levels in the tumor microenvironment often compromise the therapeutic benefits of CDT, leading to cancer recurrence and metastasis. Herein, a second near-infrared (NIR-II) photothermal Fenton nanocatalyst (PFN) was developed for activatable magnetic resonance imaging (MRI)-guided synergetic photothermal therapy (PTT) and CDT of pancreatic carcinoma. Such a PFN consists of manganese dioxide (MnO2), copper sulfide (CuS), and human serum albumin (HSA), which serve as the activatable imaging contrast agent, the NIR-II photothermal agent and Fenton catalyst, and the stabilizer, respectively. The acidic tumor microenvironment increased the relaxivity of PFN by 2.1-fold, allowing for improved imaging performance and monitoring of nanoparticle accumulation in tumors. Under NIR-II laser irradiation at 1064 nm, PFN generates local heat, which not only permits PTT but also enhances the nanocatalyst-mediated Fenton-like reaction. As such, PFN exerts a synergetic action to completely ablate xenografted tumor models in living animals, while the sole CDT fails to do so. This study thus provides an NIR-II photothermal nanocatalyst for potential treatment of deep-seated tumors.

Well-child care delivery in the community in China: Related factors and quality analysis of services.

Well-child health care services are essential for maintaining optimum child health and development. This study's aim was to evaluate the quality of such services and identify factors affecting service quality from the perspective of well-child health care providers located in China's Hunan Province. To achieve this, a qualitative descriptive method was employed, with 22 well-child health care providers being recruited, using purposive sampling, from among the provinces' government community health centers. The participants completed individual semi-structured interviews lasting approximately 25-30 minutes that were designed to obtain their views on well-child health care administration in the province. Then, the interview transcripts were analyzed thematically. The main finding was that participants felt that the delivery of well-child health care services in Hunan Province is insufficient. Factors they mentioned as negatively affecting the delivery of such services included the region's fragmented primary health care system, inadequate attention to this issue from parents and community health care center managers, and a lack of specialized well-child care knowledge. Thus, currently, well-child health care is not being successfully implemented in Hunan Province; consequently, in order to successfully implement well-child health care in this region, community health care centers should invest more resources and funding, particularly into education programs for well-child health care providers.

Prevalence of methicillin-resistant Staphylococcus aureus colonisation among healthcare workers at a tertiary care hospital in southeastern China.

OBJECTIVES: The aim of this study was to investigate the carriage rates of Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) among healthcare workers (HCWs) at a tertiary-care hospital in southeastern China and to analyse the epidemiological relatedness of the S. aureus isolates. METHODS: A total of 242 pharynx swabs were collected in March-April 2016 from 242 HCWs working in seven different wards and departments. Isolates were identified as S. aureus based on morphology, coagulase test and Vitek test. Antimicrobial susceptibility testing was performed by using the Kirby-Bauer disk diffusion method. The epidemiological relatedness of the S. aureus isolates was determined by pulsed-field gel electrophoresis (PFGE). RESULTS: From the 242 HCWs, 70 (28.9%) S. aureus strains, including 10 (4.1%) MRSA strains, were identified during screening, with the highest MRSA rate detected in nurses (8/107; 7.5%). Carriage rates of S. aureus and MRSA among surgical HCWs were 30.0% (63/210) and 4.3% (9/210), respectively. Methicillin-susceptible S. aureus (MSSA) isolates were grouped by PFGE analysis into five similar groups (A-E), with most isolates belonging to groups D and E, accounting for 63.0% of isolates. Furthermore, two MRSA isolates from gastrointestinal surgery had identical PFGE patterns. CONCLUSIONS: The prevalence of S. aureus colonisation among HCWs was high in this hospital, although the MRSA carriage rate in surgical wards was low. The identical PFGE pattern detected in two MRSA isolates from the same surgical department supports that effective control for possible cross-infection should be implemented.

Adaptation and Validation of a Chinese Version of Patient Health Engagement Scale for Patients with Chronic Disease.

The Patient Health Engagement Scale (PHE-s) was designed to assess the emotional and psychological attitudes of patients' engagement along their healthcare management journey. The aim of this study was to validate a culturally adapted Chinese version of the PHE-s (CPHE-s). Three hundred and seventy-seven participants were recruited from eight community health centers in a sample of patients with chronic disease in Hunan Province, China. The original Italian PHE-s was translated into Mandarin Chinese using a standardized forward-backward translation. The Rasch model was utilized and presented uni-dimensionality and good items fitness of the PHE-s. The internal consistency was 0.89 and the weighted Kappa coefficients of the items (test-retest reliability) ranged from 0.52 to 0.79. Both principal component analysis and confirmatory factor analysis supported a single-factor structure of the PHE-s. In testing the external validity, the PHE-s showed a significant moderate correlation with patient activation but not with medicine adherence behavior, which requires further exploration. The result suggested that the PHE-s is a reliable and valid instrument to assess the level of patient engagement in his or her own health management among chronic patients in China. Further analysis of reliability and validity should be assessed among other patient cohorts in China, and future directions for testing changes after patient engagement interventions should be developed by exploring some clinical relevance.

Levels of insulin-like growth factors and their receptors in placenta in relation to macrosomia.

OBJECTIVE: To investigate the associations between mRNA levels that encodes for insulin-like growth factors (IGFS) and their receptors in term placenta, and the risk of macrosomia. METHODS: Term placentas were collected from 37 neonates with macrosomia and 37 neonates with normal birth weight in Changzhou Women and Children Health Hospital from March 1 to June 30, 2008. The IGF mRNA levels and their receptors in those placentas were measured by Real-time PCR. RESULTS: The placental weight was positively correlated with the birth weight both in the macrosomia group (r=0.550, p=0.004) and the control group (r=0.678, p=0.000). After adjusting for potential confounders, multivariable adjusted ORs of neonates with macrosomia for those in the increasing two tertiles were 17.3 (95%CI: 2.50-19.2) and 5.94 (95%CI: 0.96, 36.8), respectively, compared with those in the lowest tertile in terms of IGF-IImRNA level. Similarly, multivariable adjusted ORs of neonates with macrosomia for those in the increasing two tertiles of IGF-IR mRNA were 25.3 (95%CI: 3.43-187) and 43.0 (95%CI: 4.89, 378), respectively. CONCLUSION: These results indicate that the levels of placental IGF-IIand IGF-IR mRNA may be involved in the development of macrosomia.