Rapid isolation of pan-neutralizing antibodies against Omicron variants from convalescent individuals infected with SARS-CoV-2.

Introduction: The emergence of SARS-CoV-2 Omicron subvariants has presented a significant challenge to global health, as these variants show resistance to most antibodies developed early in the pandemic. Therapeutic antibodies with potent efficacy to the Omicron variants are urgently demanded. Methods: Utilizing the rapid antibody discovery platform, Berkeley Lights Beacon, we isolated two monoclonal neutralizing antibodies, 2173-A6 and 3462-A4. These antibodies were isolated from individuals who recently recovered from Omicron infections. Results: Both antibodies, 2173-A6 and 3462-A4, demonstrated high affinity for the RBD and effectively neutralized pseudoviruses from various Omicron lineages, including BA.4/5, XBB.1.16, XBB.1.5, and EG.5.1. This neutralization was achieved through binding to identical or overlapping epitopes. Discussion: The use of the Beacon platform enabled the rapid isolation and identification of effective neutralizing antibodies within less than 10 days. This process significantly accelerates the development of novel therapeutic antibodies, potentially reducing the time required to respond to unknown infectious diseases in the future.

Autophagy Induced by Low Shear Stress Leads to Endothelial Glycocalyx Disruption.

INTRODUCTION: Previous studies have confirmed that low shear stress (LSS) induces glycocalyx disruption, leading to endothelial dysfunction. However, the role of autophagy in LSS-induced glycocalyx disruption and relevant mechanism are not clear. In this study, we hypothesized that LSS may promote autophagy, disrupting the endothelium glycocalyx. METHODS: Human umbilical vein endothelial cells were subjected to physiological shear stress and LSS treatments, followed by the application of autophagy inducers and inhibitors. Additionally, cells were treated with specific matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) inhibitor. The expression of autophagic markers, glycocalyx, MMP-2, and MMP-9 was measured. RESULTS: LSS impacted the expression of endothelium autophagy markers, increasing the expression of LC3II.LC3I-1 and Beclin-1, and decreasing the levels of p62, accompanied by glycocalyx disturbance. Moreover, LSS upregulated the expression of MMP-2 and MMP-9 and downregulated the levels of syndecan-1 and heparan sulfate (HS). Additionally, expression of MMP-2 and MMP-9 was increased by an autophagy promoter but was decreased by autophagy inhibitor treatment under LSS. Autophagy and MMP-2 and MMP-9 further caused glycocalyx disruption. CONCLUSION: LSS promotes autophagy, leading to glycocalyx disruption. Autophagy increases the expression of MMP-2 and MMP-9, which are correlated with the glycocalyx destruction induced by LSS.

High-throughput extraction and automatic purification of alternariol from edible and medicinal herbs based on aptamer-functionalized magnetic nanoparticles.

Mycotoxin contamination is widespread in plants and herbs, posing serious threats to the consumer and human health. Of them, alternariol (AOH) has attracted great attention as an "emerging" mycotoxin in medicinal herbs. However, a specific and high-throughput extraction method for AOH is currently lacking. Thus, developing an efficient pre-treatment technique for AOH detection is extremely vital. Here, a novel automated magnetic solid-phase extraction method was proposed for the highly efficient extraction of AOH. Combining the aptamer-functionalized magnetic nanoparticles (AMNPs) and the automatic purification instrument, AOH could be extracted in medicinal herbs in high throughput (20 samples) and a short time (30 min). The main parameters affecting extraction were optimized, and the method was finally carried out by incubation AMNPs with 3 mL of sample solution for 10 min, and then desorption in 75% methanol for liquid-phase detection. Under optimal conditions, good reproducibility, stability, and selectivity were realized with an adsorption capacity of 550.84 ng/mg. AOH extraction in three edible herbs showed good resistance to matrix interference with recovery rates from 86% to 111%. In combination with AMNPs and the automatic purification instrument, high-throughput and labor-free extraction of AOH in different complex matrices was achieved, which could be extended in other complex matrices.

A Multi-Information Spreading Model for One-Time Retweet Information in Complex Networks.

In the realm of online social networks, the spreading of information is influenced by a complex interplay of factors. To explore the dynamics of one-time retweet information spreading, we propose a Susceptible-Infected-Completed (SIC) multi-information spreading model. This model captures how multiple pieces of information interact in online social networks by introducing inhibiting and enhancement factors. The SIC model considers the completed state, where nodes cease to spread a particular piece of information after transmitting it. It also takes into account the impact of past and present information received from neighboring nodes, dynamically calculating the probability of nodes spreading each piece of information at any given moment. To analyze the dynamics of multiple information pieces in various scenarios, such as mutual enhancement, partial competition, complete competition, and coexistence of competition and enhancement, we conduct experiments on BA scale-free networks and the Twitter network. Our findings reveal that competing information decreases the likelihood of its spread while cooperating information amplifies the spreading of mutually beneficial content. Furthermore, the strength of the enhancement factor between different information pieces determines their spread when competition and cooperation coexist. These insights offer a fresh perspective for understanding the patterns of information propagation in multiple contexts.

Lateral Flow Assays Biotesting by Utilizing Plasmonic Nanoparticles Made of Inexpensive Metals - Replacing Colloidal Gold.

Nanoparticles (NPs) can be conjugated with diverse biomolecules and employed in biosensing to detect target analytes in biological samples. This proven concept was primarily used during the COVID-19 pandemic with gold NPs-based lateral flow assays (LFAs). Considering the gold price and its worldwide depletion, here we show that novel plasmonic nanoparticles (NPs) based on inexpensive metals, titanium nitride (TiN) and copper covered with a gold shell (Cu@Au), perform comparable or even better than gold nanoparticles. After conjugation, these novel nanoparticles provided high figures of merit for LFA testing, such as high signals and specificity and robust naked-eye signal recognition. To the best of our knowledge, our study represents the 1st application of laser-ablation-fabricated nanoparticles (TiN) in the LFA and dot-blot biotesting. Since the main cost of the Au NPs in commercial testing kits is in the colloidal synthesis, our development with TiN is very exciting, offering potentially very inexpensive plasmonic nanomaterials for various bio-testing applications. Moreover, our machine learning study showed that the bio-detection with TiN is more accurate than that with Au.

Insulin Infusion Protocols for Blood Glucose Management in Critically Ill Patients: A Scoping Review.

BACKGROUND: Continuous insulin infusion is a method for maintaining blood glucose stability in critically ill patients with hyperglycemia. Many insulin infusion protocols have been applied in intensive care units. Understanding the content of these protocols can help clinical staff choose the most appropriate and convenient protocol and promote best practices in managing glucose levels in critically ill adult patients. OBJECTIVE: To examine the types of insulin infusion therapies performed for blood glucose management in critically ill patients. METHODS: For this scoping review, 3 Chinese-language and 8 English-language databases were searched for articles published from May 25, 2016, to October 25, 2022. RESULTS: Twenty-one articles met the inclusion criteria. Twenty-one insulin infusion protocols were examined. Most of the insulin infusion protocols were paper protocols. Fourteen glucose management indicators were included in the 21 protocols. The glucose target range for all 21 protocols ranged from 70 to 180 mg/dL (3.9-10.0 mmol/L). Nurses were primarily responsible for protocol implementation in most protocol development processes. The roles of nurses differed in nurse-led insulin infusion protocols and non-nurse-led insulin infusion protocols. DISCUSSION: This scoping review indicates an urgent need for more comprehensive glycemic control guidelines for patients receiving critical care. Because insulin infusion protocols are core aspects of blood glucose management guidelines, different population subgroups should also be considered. CONCLUSIONS: Nurse-led guidelines must be based on the best available evidence and should include other variables related to glucose management (eg, patient disease type, medication, and nutrition) in addition to insulin infusion.

Effect of serum uric acid and gout on the incidence of colorectal cancer: A meta-analysis.

OBJECTIVE: Pathogenesis of colorectal cancer (CRC) depends on multiple factors. Identifying risk factors for CRC may facilitate the early prevention of the disease. We aimed to assess whether existing evidence suggests that serum uric acid (SUA) levels and gout are associated with CRC incidence. METHODS: The study was registered on PROSPERO (CRD42022371591). Searches of PubMed, Embase, and Cochrane Library were conducted from the establishment to November 11, 2022. Pooled relative risk (RR) with 95 % confidence intervals (CI) was derived to evaluate the effect of SUA or gout on CRC incidence. Non-linear trend analysis was conducted to explore the relationship between SUA level and CRC incidence. RESULTS: Twelve eligible studies with 22 reports were included. A meta-analysis of the included studies showed that when the highest and lowest SUA level categories were compared, an association between SUA level and CRC incidence was revealed (RR, 1.35; 95 % CI: 1.27-1.43; P < 0.001). Non-linear relationship between SUA level and CRC incidence was found. Further meta-analysis indicated that gout was associated with CRC incidence (RR, 1.22; 95 % CI: 1.08-1.36; P = 0.001). CONCLUSIONS: Both SUA level and gout were associated with an increased risk of CRC. Maintaining low SUA levels may be beneficial in reducing the incidence of CRC. Further studies evaluating the precise mechanisms underlying this association are needed to establish whether SUA/gout causes CRC.

Association between gout and the risk of osteoporosis and fractures: a meta-analysis.

OBJECTIVE: The relationship between gout and osteoporosis is poorly clarified, and the association between gout and fractures incidence remains controversial. Hence, in the present study, we aimed to comprehensively evaluate the available literature to elucidate whether gout is associated with an increased risk of both osteoporosis and fractures. MATERIALS AND METHODS: We conducted an exhaustive search of pertinent literature published until 20 March 2023, in well-recognized databases, namely Medline, Embase and Cochrane Library, focusing on examining the association between gout and the risk of osteoporosis or fracture. Meta-analysis was performed to aggregate the relative risks (RR) using random- or fixed-effects models. Sensitivity analyses were conducted iteratively, whereby each study was removed sequentially to gauge its impact on the overall outcome. Publication bias was assessed using Egger's and Begg's tests. This study was registered with PROSPERO (registry number: CRD42022376822). RESULTS: Herein, we included 10 observational studies comprising a total of 1,606,095 participants. An independent population sample of four studies validated the significant association between gout and osteoporosis (RR = 1.25, 95% confidence interval [CI] 1.05-1.48), with the results demonstrating robustness. However, our analysis did not detect any association between gout and fracture risk when compared with the control group (RR = 1.09, 95%CI 0.99-1.19), along with high heterogeneity (p for heterogeneity = 0.000; I2 = 79.7%). Further subgroup analysis revealed that gout is positively associated with fracture risk in the Chinese population (RR = 1.17, 95%CI 1.14-1.21), with no evidence of heterogeneity (p for heterogeneity = 0.420; I2 = 0.00%). CONCLUSION: Our meticulous evaluation of the available literature indicates that gout has no discernible impact on fracture incidence, although it is positively associated with an enhanced risk of osteoporosis. Therefore, it is imperative to prioritize preventive measures to prevent osteoporotic complications in individuals diagnosed with gout.

Staff knowledge, attitudes and practices regarding glycaemic management in adult intensive care units: A national survey.

BACKGROUND: Hyperglycaemia is common in critically ill adult patients. Many studies have identified the content, methods, and effects of glycaemic control but have not explored the effects of knowledge, attitudes, and practices (KAP) on glycaemic control in critically ill adults. Various factors also influence the KAP of intensive care unit (ICU) staff. AIMS: To assess KAP regarding glucose management for critically ill adults among nurses and medical professionals and identify the factors that influence their KAP in ICUs. METHODS: A multicentre cross-sectional survey. RESULTS: In total, 403/459 (response rate: 87.8%) participants from ICUs in nine tertiary hospitals in China participated in this study, 82.4% of whom were female and 93.4% of whom were nurses. The mean work experience was 8.88 years, and the mean critical care experience was 6.59 years. The scoring rate for the three dimensions of knowledge, attitudes, and practices were 82.35%, 87.69%, and 76%, respectively. We did not find any other factors affecting the KAP scores except for the level of knowledge awareness (p < 0.001), awareness of the importance (p < 0.001), and training for glucose control (p = 0.004). CONCLUSION: ICU staff KAP regarding glycaemic control in critically ill adults among ICU professionals were acceptable in China. However, ICU professionals' current knowledge regarding nutrition, glucose variability, and skills related to glucose management could be improved. RELEVANCE TO CLINICAL PRACTICE: ICU educators should provide more skills-related training for healthcare professionals in the glycaemic management of critically ill adults. Moreover, the process of managing blood glucose in adult ICU patients is a collaborative, multidisciplinary team effort, with monitoring and feedback required during implementation.

miR-5581 Contributes to Osteoarthritis by Targeting NRF1 to Disturb the Proliferation and Functions of Chondrocytes.

Chondrocyte survival is critical for the preservation of a healthy cartilage matrix. Limited chondrocyte function and survival can result in articular cartilage failure, thereby contributing to osteoarthritis (OA). In this study, miR-5581 was significantly up-regulated in OA samples, and miR-5581-associated genes were enriched in Kras signaling. miR-5581 up-regulation was observed in clinical OA samples and IL-1ß-stimulated chondrocytes. miR-5581 inhibition attenuated IL-1ß-induced chondrocyte proliferation suppression, extracellular matrix (ECM) synthesis suppression and degradation, and IL-1ß-suppressed Kras signaling activation. miR-5581 was targeted to inhibit NRF1. In IL-1ß-treated chondrocytes, NRF1 overexpression attenuated IL-1ß-induced cellular damage and partially abolished the effects of miR-5581 overexpression on IL-1ß-stimulated chondrocytes. NRF1 was down-regulated in knee joint cartilage of OA mice. In conclusion, miR-5581, which was up-regulated in OA samples and IL-1ß-stimulated chondrocytes, inhibited chondrocyte proliferation and ECM synthesis, and promoted ECM degradation through targeting NRF1, whereby Kras signaling might be involved.

An alkali-enhanced subcritical water treatment strategy of short-chain chlorinated paraffins: Dechlorination and hydrocarbons recovery.

As persistent organic pollutants, short-chain chlorinated paraffins (SCCPs) have attracted wide attention in the field of environmental health risk and hazardous waste management. Efficient dechlorination of high content of SCCPs in plastic waste is the committed step for its detoxification and safety treatment. In this study, a high-efficiency and low-temperature process for dechlorination and hydrocarbons recovery from typical SCCPs (52#SCCPs) by subcritical water (SubCW) with alkali enhancer was developed. The introduction of alkali enhancer in the SubCW process had significantly enhanced effect on the dechlorination of 52#SCCPs, and the order of the enhanced effect of alkali enhancer for the dechlorination was NaOH > Na2CO3 > NaHCO3 > NH3·H2O > KOH. The dechlorination behaviors of 52#SCCPs in the NaOH-enhanced SubCW process were studied systematically under different conditions including temperature, residence time, alkali concentration, and volume ratio. The results showed that high-efficiency dechlorination (100 %) of 52#SCCPs could be achieved by the NaOH-enhanced SubCW process at low temperature for a short time (250 °C, 5 min). All of the chlorine released from the molecular chain of 52#SCCPs was transferred to the aqueous phase in the form of inorganic chlorine. The continuous HCl elimination reaction was the primary dechlorination mechanism for 52#SCCPs in the NaOH-enhanced SubCW process. After the dechlorination of 52#SCCPs, high value-added hydrocarbons such as 2,4-hexadiyne (31.74 %) could be obtained. The alkali-enhanced SubCW process proposed in this study is believed to be an environmentally friendly and high-efficiency method for dechlorination/detoxification and resource recovery of SCCPs.

The analysis of reliability and validity of a competency evaluation model for front-line nursing staff during the outbreak of major infectious diseases.

BACKGROUND: Outbreaks of major infectious diseases represent a tremendous threat to people's health, safety and property, yet little is known about the competence of front-line caregivers in such situations. AIM: To construct a model for evaluating the competency of front-line nursing staff during major infectious disease outbreaks and to test the model's reliability and validity. STUDY DESIGN: This was a cross-sectional study that took place between November and December 2021, in Chinese hospitals. The model was constructed through literature reviews, descriptive qualitative research, the Delphi method and the analytic hierarchy process. To evaluate the model's validity and reliability, 550 front-line nurses were selected to complete a questionnaire survey, and six experts were invited to conduct a content validity evaluation. Cronbach's α coefficient was used to test the model's reliability, while an exploratory factor analysis was used to measure the structural validity of the model. RESULTS: The model included 57 items. The Cronbach's α coefficient of the model was 0.983, and the content validity index was 0.958. Six common factors were produced by exploratory factor analysis. The cumulative variance contribution rate was 66.718%. After discussion, the original four dimensions were maintained. CONCLUSION: The model for evaluating the competency of front-line nursing staff during an outbreak of major infectious diseases has strong reliability and validity and can be used as a tool to assess the competency level of front-line nursing staff. RELEVANCE TO CLINICAL PRACTICE: This model can provide a useful reference for care managers to accurately evaluate, train and select caregivers during an epidemic.

Detection of Mildewed Nutmeg Internal Quality during Storage Using an Electronic Nose Combined with Chemical Profile Analysis.

Internal mildewed nutmeg is difficult to perceive without cutting the nutmeg open and examining it carefully, which poses a significant risk to public health. At present, macroscopic identification and chromatographic analysis are applied to determine whether nutmeg is moldy or not. However, the former relies on a human panel, with the disadvantages of subjectivity and empirical dependence, whilst the latter is generally time-consuming and requires organic solvents. Therefore, it is urgent to develop a rapid and feasible approach for evaluating the quality and predicting mildew in nutmeg. In this study, the quality and odor characteristics of five groups of nutmeg samples with different degrees of mildew were analyzed by using the responses of an electronic nose combined with chemical profiling. The main physicochemical indicators, such as the levels of α-pinene, ß-pinene, elemicin, and dehydro-di-isoeugenol, were determined. The results revealed that the contents of α-pinene, ß-pinene, and elemicin changed significantly with the extension of storage time. Through the use of an electronic nose and HS-GC-MS technology to assess the overall odor characteristics of nutmeg samples, it was found that the production of volatile organic compounds (VOCs) such as ammonia/organic amines, carbon monoxide, ethanol, and hydrogen sulfide, as well as changes in the terpene and phenylpropene components of the nutmeg itself, may be the material basis for the changes in odor. The accuracy of the qualitative classification model for the degree of mildew in nutmeg was higher than 90% according to the electronic nose data combined with different machine learning algorithms. Quantitative models were established for predicting the contents of the chemical components, and models based on a BP neural network (BPNN), the support vector machine (SVM), and the random forest algorithm (RF) all showed good performance in predicting the concentrations of these chemical components, except for dehydro-di-isoeugenol. The BPNN performed effectively in predicting the storage time of nutmeg on the basis of the E-nose's responses, with an RMSE and R2 of 0.268 and 0.996 for the training set, and 0.317 and 0.993 for the testing set, respectively. The results demonstrated that the responses of the electronic nose (E-nose) had a high correlation with the internal quality of nutmeg. This work proposes a quick and non-destructive evaluation method for the quality of nutmeg, which has high accuracy in discriminating between different degrees of mold in nutmeg and is conducive to early detection and warning of moldy phenomena.

Single-Cell RNA Sequencing and Transcriptome Analysis Revealed the Immune Microenvironment and Gene Markers of Acute Respiratory Distress Syndrome.

Background: Acute respiratory distress syndrome (ARDS) is caused by severe pulmonary inflammation and the leading cause of death in the intensive care unit. Methods: We used single-cell RNA sequencing to compare peripheral blood mononuclear cells from sepsis-induced ARDS (SEP-ARDS) and pneumonic ARDS (PNE-ARDS) patient. Then, we used the GSE152978 and GSE152979 datasets to identify molecular dysregulation mechanisms at the transcriptional level in ARDS. Results: Markedly increased CD14 cells were the predominant immune cell type observed in SEP-ARDS and PNE-ARDS patients. Cytotoxic cells and natural killer (NK) T cells were exclusively identified in patients with PNE-ARDS. An enrichment analysis of differentially expressed genes (DEGs) suggested that Th1 cell differentiation and Th2 cell differentiation were enriched in cytotoxic cells, and that the IL-17 signaling pathway, NOD receptor signaling pathway, and complement and coagulation cascades were enriched in CD14 cells. Furthermore, according to GSE152978 and GSE152979, 1939 DEGs were identified in patients with ARDS and controls; they were mainly enriched in the Kyoto Encyclopedia of Genes and Genomes pathways. RBP7 had the highest area under the curve values among the 12 hub genes and was mainly expressed in CD14 cells. Additionally, hub genes were negatively correlated with NK cells and positively correlated with neutrophils, cytotoxic cells, B cells, and macrophages. Conclusion: A severe imbalance in the proportion of immune cells and immune dysfunction were observed in SEP-ARDS and PNE-ARDS patients. RBP7 may be immunologically associated with CD14 cells and serve as a potential marker of ARDS.

Connection between right-to-left shunt and photosensitivity: a community-based cross-sectional study.

Background: Hypersensitivity to light is a common symptom associated with dysfunction of the occipital region. Earlier studies also suggested that clinically significant right-to-left shunt (RLS) could increase occipital cortical excitability associated with the occurrence of migraine. The aim of this study was to investigate the relationship between RLS and photosensitivity. Methods: This cross-sectional observational study included the residents aged 18-55 years living in the Mianzhu community between November 2021 and October 2022. Photosensitivity was evaluated using the Photosensitivity Assessment Questionnaire along with baseline clinical data through face-to-face interviews. After the interviews, contrast-transthoracic echocardiography (cTTE) was performed to detect RLS. Inverse probability weighting (IPW) was used to reduce selection bias. Photosensitivity score was compared between individuals with and without significant RLS using multivariable linear regression based on IPW. Results: A total of 829 participants containing 759 healthy controls and 70 migraineurs were finally included in the analysis. Multivariable linear regression analysis showed that migraine (ß = 0.422; 95% CI: 0.086-0.759; p = 0.014) and clinically significant RLS (ß = 1.115; 95% CI: 0.760-1.470; p < 0.001) were related to higher photosensitivity score. Subgroup analysis revealed that clinically significant RLS had a positive effect on hypersensitivity to light in the healthy population (ß = 0.763; 95% CI: 0.332-1.195; p < 0.001) or migraineurs (ß = 1.459; 95% CI: 0.271-2.647; p = 0.010). There was also a significant interaction between RLS and migraine for the association with photophobia (pinteraction = 0.009). Conclusion: RLS is associated with photosensitivity independently and might exacerbate photophobia in migraineurs. Future studies with RLS closure are needed to validate the findings. Trial registration: This study was registered at the Chinese Clinical Trial Register, Natural Population Cohort Study of West China Hospital of Sichuan University, ID: ChiCTR1900024623, URL: https://www.chictr.org.cn/showproj.html?proj=40590.

Efficacy of ultrasound-guided bilateral costal margin block in laparoscopy-assisted gastrectomy: A double-blind randomized trial.

BACKGROUND: Ultrasound-guided costal margin block (CMB) is a superficial and easily applicable technique. The current study aims to investigate its analgesic efficacy in patients undergoing laparoscopy-assisted gastrectomy and describe its feasibility. METHODS: Forty-two patients undergoing laparoscopy-assisted gastrectomy were enrolled in this prospective, double-blind, randomized clinical trial. Patients were randomized to receive standard general anesthesia with (block group, n = 21) or without (control group, n = 21) ultrasound-guided bilateral CMB. The primary outcome was 24-h intravenous morphine equivalents after surgery. Secondary outcomes included consumption of titrated morphine, 24-48 h morphine equivalents, consumption of intraoperative remifentanil, numerical pain rating scale scores, time to first opioid dose, patient satisfaction, adverse effects, and recovery events. RESULTS: The postoperative 24-h morphine equivalents in the block group were significantly reduced compared to the control group (14.4 ± 7.4 mg vs. 29.9 ± 9.8 mg, p < 0.001). Both the titrated morphine consumption in the post-anesthesia care unit (PACU) and intraoperative remifentanil consumption were lower in the block group than in the control group. Patients in the block group had relatively lower average pain scores in PACU and reported more satisfaction with pain relief. Adverse effects and hospital length of stay after surgery were comparable between the two groups (p > 0.05). CONCLUSION: As a novel and easily-performed technique, ultrasound-guided bilateral CMB can reduce opioid consumption in patients undergoing laparoscopy-assisted gastrectomy.

The effect of 12 week-maximum fat oxidation intensity (FATmax) exercise on microvascular function in obese patients with nonalcoholic fatty liver disease and its mechanism.

Fifty-four obese patients with non-alcoholic fatty liver disease (NAFLD) were selected for this study were randomly divided into an exercise group (16 men and 11 women, mean age 21.3 ± 1.0) and control group (16 men and 11 women, mean age 21.8 ± 0.8). The exercise group underwent a 12-week FATmax exercise intervention, while the control group did not engage in any type of systematic physical activity. The controlled diet was given to both groups. After the test, the microvascular reactivity of the exercise group was significantly higher than that of the control group (p < 0.05). After the experiment, the concentration of malondialdehyde (MDA), the activity of catalase (CAT) and the activity of exercise group were significantly lower than those of the control group (p < 0.05); and in contrast the activities of total superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) were significantly higher than those of the control group (p< 0.05). The change in microcirculation function caused by 12-week FATmax intensity exercise may have an interaction mechanism with oxidative stress and antioxidant system function, and may improve the microvascular reactivity of obese NAFLD patients. In addition, also may improve of oxidative stress and antioxidant system functions.

Recent progress in aptamer and CRISPR-Cas12a based systems for non-nucleic target detection.

Efficient and sensitive detection of targets is one of the motivations for constant development and innovation of various biosensors. CRISPR-Cas12a, a new generation of gene editing tools, has shown excellent application potential in biosensor design and construction. By combining with the specific recognition element-aptamer, a single-stranded oligonucleotide obtained by systematic evolution of ligands by exponential enrichment (SELEX) in vitro screening, CRISPR-Cas12a also shows superior performance non-nucleic acid targets detection, such as small molecules, proteins, virus and pathogenic bacteria. However, aptamer and CRISPR-Cas12a (CRISPR-Cas12a/Apt) still face some problems in non-nucleic acid target detection, such as single signal response mode and narrow linear range. The development of diverse CRISPR-Cas12a/Apt biosensors is necessary to meet the needs of various detection environments. In this review, the working principle of CRISPR-Cas12a/Apt was introduced and recent progress in CRISPR-Cas12a/Apt in the application of non-nucleic acid target detection was summarized. Moreover, the requirements of critical parameters such as crRNA sequence, activator sequence, and reaction system in the design of CRISPR-Cas12a/Apt biosensors were discussed, which could provide the reference for the design of efficient and sensitive novel non-nucleic acid target biosensors. In addition, the challenges and prospects of CRISPR-Cas12a/Apt-based biosensor were further presented.

High expression of TARS is associated with poor prognosis of endometrial cancer.

INTRODUCTION: Endometrial cancer is the second largest and most common cancer in the world. It is urgent to explore novel biomarkers. METHODS: Data were obtained from The Cancer Genome Atlas (TCGA) database. The receiver operating characteristic (ROC) curves, Kaplan-Meier curves and Cox analysis, nomograms, gene set enrichment analysis (GSEA) were conducted. Cell proliferation experiments were performed in Ishikawa cell. RESULTS: TARS was significantly highly expressed in serous type, G3 grade, and deceased status. Significant association was between high TARS expression with poor overall survival (P = 0.0012) and poor disease specific survival (P = 0.0034). Significant differences were observed in advanced stage, G3 and G4, and old. The stage, diabetes, histologic grade, and TARS expression showed independent prognostic value for overall survival of endometrial cancer. The stage, histologic grade, and TARS expression showed independent prognostic value for disease specific survival of endometrial cancer. Activated CD4+ T cell, effector memory CD4+ T cell, memory B cell and type 2 T helper cell may participate in the high TARS expression related immune response in endometrial cancer. The CCK-8 results showed significantly inhibited cell proliferation in si-TARS (P < 0.05) and promoted cell proliferation in O-TARS (P < 0.05), confirmed by the colony formation and live/dead staining. CONCLUSION: High TARS expression was found in endometrial cancer with prognostic and predictive value. This study will provide new biomarker TARS for diagnosis and prognosis of endometrial cancer.

Effects of different heavy metal pollution levels on microbial community structure and risk assessment in Zn-Pb mining soils.

Heavy metal contamination in soils seriously threatens human health and aggravates the global pollution burden. In this study, we investigated the risk of heavy metal contamination in soils at a Zn-Pb mineral processing plant in Longnan, China, and the effects of different heavy metal contamination levels on diverse microbial communities. Statistical analysis showed that, except for Ni, the average content of all detected metals (Zn, Pb, As, Cu, Cd, Hg) in the soil was higher than the background value of soil in the study area, which was most seriously contaminated with Pb and As. Comparison of functional divisions showed that heavy metal soil contamination was most serious in the raw material stacking area and the production area. Interpolation analysis showed that areas closer to the wastewater discharge area had higher contents of each heavy metal and were more seriously polluted. From the point of pollution index, the risk of heavy metal soil pollution in the study area was very high (RI = 2845.24, i.e., > 600), with Cd and Hg being the most serious pollutants compared with other heavy metals. Microbial community abundance, diversity, and structure differed at different levels of heavy metal contamination. The community diversity of bacteria decreased with increasing heavy metal concentrations, while no significant change in fungi was observed. Evidence from variation redundancy analysis (RDA) and the Spearman correlation analysis showed that the leading factors affecting microbial community composition were Cu, Cd, Hg, and pH. Actinobacteria and Gemmatimonadetes at the uncontaminated level (CL) were significantly and negatively correlated with the concentrations of Cu, Zn, Cd, and Pb. Proteobacteria and Chloroflexi at the severely contaminated level (SL) were significantly correlated with pH and Hg. However, heavy metal contamination had less effect on most of the dominant fungi. In conclusion, microbial communities such as Proteobacteria, Actinobacteria, Chloroflexi, and Ascomycota showed greater tolerance to heavy metals. These results could be used as important references for the remediation of heavy metal-contaminated soils.