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Abstract Background Childhood maltreatment (CM) is linked to long-term adverse health outcomes, including accelerated biological aging and cognitive decline. This study investigates the relationship between CM and various aging biomarkers: telomere length, facial aging, intrinsic epigenetic age acceleration (IEAA), GrimAge, HannumAge, PhenoAge, frailty index, and cognitive performance. Methods We conducted a Mendelian randomization (MR) study using published GWAS summary statistics. Aging biomarkers included telomere length (qPCR), facial aging (subjective evaluation), and epigenetic age markers (HannumAge, IEAA, GrimAge, PhenoAge). The frailty index was calculated from clinical assessments, and cognitive performance was evaluated with standardized tests. Analyses included Inverse-Variance Weighted (IVW), MR Egger, and Weighted Median (WM) methods, adjusted for multiple comparisons. Results CM was significantly associated with shorter telomere length (IVW: β = − 0.1, 95% CI − 0.18 to − 0.02, pFDR = 0.032) and increased HannumAge (IVW: β = 1.33, 95% CI 0.36 to 2.3, pFDR = 0.028), GrimAge (IVW: β = 1.19, 95% CI 0.19 to 2.2, pFDR = 0.040), and PhenoAge (IVW: β = 1.4, 95% CI 0.12 to 2.68, pFDR = 0.053). A significant association was also found with the frailty index (IVW: β = 0.31, 95% CI 0.13 to 0.49, pFDR = 0.006). No significant associations were found with facial aging, IEAA, or cognitive performance. Conclusions CM is linked to accelerated biological aging, shown by shorter telomere length and increased epigenetic aging markers. CM was also associated with increased frailty, highlighting the need for early interventions to mitigate long-term effects. Further research should explore mechanisms and prevention strategies.

Summary: Clinical research indicates that SARS-CoV-2 infection is linked to several neurological consequences, and the virus is still spreading despite the availability of vaccinations and antiviral medications. To determine how hosts respond to SARS-CoV-2 infection, we employed LC-MS/MS to perform ubiquitinome and proteome analyses of the brain cortexes from K18-hACE2 mice in the presence and absence of SARS-CoV-2 infection. A total of 8,024 quantifiable proteins and 5,220 quantifiable lysine ubiquitination (Kub) sites in 2023 proteins were found. Glutamatergic synapse, calcium signaling pathway, and long-term potentiation may all play roles in the neurological consequences of SARS-CoV-2 infection. Then, we observed possible interactions between 26 SARS-CoV-2 proteins/E3 ubiquitin-protein ligases/deubiquitinases and several differentially expressed mouse proteins or Kub sites. We present the first description of the brain cortex ubiquitinome in K18-hACE2 mice, laying the groundwork for further investigation into the pathogenic processes and treatment options for neurological dysfunction following SARS-CoV-2 infection.

Abstract Persistent infection with high-risk human papillomavirus (HR-HPV) is the primary and initiating factor for cervical cancer. With over 200 identified HPV types, including 14 high-risk types that integrate into the host cervical epithelial cell DNA, early determination of HPV infection type is crucial for effective risk stratification and management. Presently, on-site immediate testing during the HPV screening stage, known as Point of Care Testing (POCT), remains immature, severely limiting the scope and scenarios of HPV screening. This study, guided by the genomic sequence patterns of HPV, established a multiplex recombinase polymerase amplification (RPA) technology based on the concept of “universal primers.” This approach achieved the multiple amplification of RPA, coupled with the CRISPR/Cas12a system serving as a medium for signal amplification and conversion. The study successfully constructed a POCT combined detection system, denoted as H-MRC12a (HPV—Multiple RPA—CRISPR/Cas12a), and applied it to high-risk HPV typing detection. The system accomplished the typing detection of six high-risk HPV types (16, 18, 31, 33, 35, and 45) can be completed within 40 min, and the entire process, from sample loading to result interpretation, can be accomplished within 45 min, with a detection depth reaching 1 copy/μL for each high-risk type. Validation of the H-MRC12a detection system’s reproducibility and specificity was further conducted through QPCR on 34 clinical samples. Additionally, this study explored and optimized the multiplex RPA amplification system and CRISPR system at the molecular mechanism level. Furthermore, the primer design strategy developed in this study offers the potential to enhance the throughput of H-MRC12a detection while ensuring sensitivity, providing a novel research avenue for high-throughput detection in Point-of-Care molecular pathogen studies.

The rapid and large-scale renewable energy development poses new challenges for the traditional power grid, particularly with the increasing utilization of high-power electronic interfaces. To address this, a novel grid simulator topology and its control strategy are proposed, which can generate various required waveforms with high performance. The grid simulator adopts a modular multilevel structure, a three-phase PWM module, and an H-bridge module with a shared DC bus. Model predictive control (MPC) outputs high-quality, fast voltage waveforms for accurate voltage tracking. Additionally, the model reference adaptive control (MRAC) is integrated into the PWM converter in the pre-stage to estimate the network side inductance value, which is used to improve the system’s robustness. Moreover, a switching distribution method is proposed for feedforward control to enhance reliability. Through simulation and experiment, it is verified that the proposed power grid simulator and its control strategy can effectively and accurately generate various fault waveforms such as voltage drop, voltage abrupt change, and abrupt frequency change. As a result, it can be used as test equipment for renewable energy or power electronic equipment.

Introduction: Electric bicycles (e-bikes) and bicycles in large Chinese cities have recently witnessed substantial growth in ridership. According to related accident trends, this study analyzed characteristics and spatial distribution in the period when e-bike-related accidents rapidly increased to propose priority measures to reduce accident casualties. Methods: For e-bike- and bicycle-related accident data from the Guangzhou Public Security Traffic Management Integrated System, linear regression was used to examine the trends in the number of accidents and age-adjusted road traffic casualties from 2011 to 2021. Then, for the period when e-bike-related accidents rapidly increased, descriptive statistics were computed regarding rider characteristics, illegal behaviors, road types, collision objects and their accident liability. One-way analysis of variance (ANOVA) followed by Bonferroni's multiple comparison test. P

Currently, in the field of biomedical named entity recognition, CharCNN (Character-level Convolutional Neural Networks) or CharRNN (Character-level Recurrent Neural Network) is typically used independently to extract character features. However, this approach does not consider the complementary capabilities between them and only concatenates word features, ignoring the feature information during the process of word integration. Based on this, this paper proposes a method of multi-cross attention feature fusion. First, DistilBioBERT and CharCNN and CharLSTM are used to perform cross-attention word-char (word features and character features) fusion separately. Then, the two feature vectors obtained from cross-attention fusion are fused again through cross-attention to obtain the final feature vector. Subsequently, a BiLSTM is introduced with a multi-head attention mechanism to enhance the model's ability to focus on key information features and further improve model performance. Finally, the output layer is used to output the final result. Experimental results show that the proposed model achieves the best F1 values of 90.76%, 89.79%, 94.98%, 80.27% and 88.84% on NCBI-Disease, BC5CDR-Disease, BC5CDR-Chem, JNLPBA and BC2GM biomedical datasets respectively. This indicates that our model can capture richer semantic features and improve the ability to recognize entities.

The molybdenum grade is 0.21% and the lead grade is 0.0049% in a low grade disseminated molybdenite ore in Qinghai Province. Process mineralogy research and beneficiability condition test were carried out for the low grade molybdenum ore. Diesel oil was used as collector and sodium silicate was used as regulator. After flotation process of one stage roughing, five stages cleaning and two stages scavenging, the Pb content of molybdenum concentrate obtained was 0.98%. The sale price of molybdenum mines was affected due to exceed standards lead levels. In order to reduce the lead content of the molybdenum concentrate, the process of regrinding and detoxification combined with the addition of phosphoknox, an inhibitor of inhibiting lead, was adopted for the molybdenum concentrate containing excessive lead. Finally, the lead content of molybdenum concentrate was reduced from 0.98% to 0.074%, molybdenum grade is increased from 0.21% to 53.95%, molybdenum recovery reached 90.18%, realizing effective recovery of molybdenum.

Rheumatoid Arthritis (RA) remains a major global public health challenge. Disease-modifying anti-rheumatic drugs (DMARDs) are standard therapeutic drugs for RA. Conventional DMARDs (c-DMARDs) are a subgroup of approved synthetic DMARDs. The c-DMARDs experienced lesser response with longer disease duration or drug exposure, and unwanted adverse events (AEs). The combination treatments (CTs) of c-DMARDs and Chinese Herbal Medicines (CHMs) were often used in RA clinical trials for increasing the therapeutic effectiveness and reducing the AEs. This systematic review aimed to evaluate the efficacy and safety of the CTs for RA. Databases were searched from inception to October 2020 for identification of randomized controlled trials (RCTs) that investigated the CTs in the management of RA. Twenty-three RCTs with 2,441 participants were included. The assessments and analyses found CTs improved American College of Rheumatology (ACR) 20 (RR: 1.33, 95% CI [1.21, 1.45], 10 studies, n=1,075) and alleviated AEs (RR: -0.40, 95% CI [-0.30, -0.53], 19 studies, n=2,011) in comparison with c-DMARDs. The CTs also significantly improved RA symptoms and patient-reported outcomes; reduced disease activity score (DAS) 28, serum acute-phase reactants and RA biomarkers. The five most commonly used herbs in included studies were Angelicae Sinensis Radix, Paeoniae Radix Alba, Cinnamomi Ramulus, Glycyrrhizae Radix et Rhizoma, and Clematidis Radix et Rhizoma. Pharmacological studies indicated these CHMs could contribute to the outcomes. The integrated CHMs potentially increased the overall effectiveness of c-DMARDs and alleviated AEs in management of RA. Large sample and rigorously designed RCTs are required for future studies.

Background: Statins, a first-line therapeutic option for atherosclerotic cardiovascular disease (ASCVD), have prompted concerns regarding dysglycemia and diabetes, thus posing a dilemma in treating patients with prediabetes. Xuezhikang (XZK) decreases blood cholesterol levels without affecting glucose metabolism, and may serve as a potential substitute. Methods: The XTREME study is a prospective, randomized, open-label, multi-center trial evaluating whether XZK 1200 mg/d, compared with atorvastatin 20 mg/d, has favorable effects on HbA1c levels after 24 weeks of treatment in patients with dyslipidemia and prediabetes. After a 1-week run-in period for adherence assessment, the study will randomly assign (1:1) 392 patients meeting the protocol inclusion criteria to one of two treatment groups: an experimental group (XZK 1200 mg/day) or a control group (atorvastatin 20 mg/day). All participants will be recruited from approximately 20 Chinese medical centers. The last participant is planned to be recruited before December 2023. The primary endpoint will be change in HbA1c level from baseline to 24 weeks, or before anti-diabetic therapy initiation within 24 weeks. The key secondary outcomes will include other biomarkers reflecting blood glucose or lipid metabolism. Discussion: Delaying diabetes is desirable for individuals with prediabetes. The XTREME trial presents a unique opportunity to demonstrate whether XZK might provide an alternative to statins for patients with dyslipidemia and prediabetes.

Abstract Background Long-term prophylactic therapy is considered the standard of care for hemophilia A patients. This study models the long-term clinical and cost outcomes of two factor VIII (FVIII) products using a pharmacokinetic (PK) simulation model in a Chinese population. Methods Head-to-head PK profile data of BAY 81–8973 (KOVALTRY®) and antihemophilic factor (recombinant) plasma/albumin-free method (rAHF-PFM, ADVATE®) were applied to a two-state (alive and dead) Markov model to simulate blood FVIII concentrations at a steady state in prophylactically-treated patients with hemophilia A. Worsening of the Pettersson score was simulated and decline was associated with the probability of having orthopaedic surgery. The only difference between the compounds was FVIII concentration at a given time; each subject was treated with 25 IU/kg every 3 days. The model used a lifetime horizon, with cycle lengths of 1 year. Results Cumulative bleeding events, joint bleeding events, and major bleeding events were reduced by 19.3% for BAY 81–8973 compared to rAHF-PFM. Hospitalizations and hospitalization days were also reduced by 19.3% for BAY 81–8973 compared to rAHF-PFM. BAY 81–8973 resulted in both cost savings and a gain in quality adjusted life years (QALYs) compared to rAHF-PFM. Conclusion Based on modeled head-to-head comparisons, differences in PK-properties between BAY 81–8973 and rAHF-PFM result in a reduced number of bleeding events, leading to reduced costs and increased quality of life for BAY 81–8973. These results should be used to inform clinical practice in China when caring for patients with severe hemophilia A.

Abstract Exposure to heavy metals (HMs) is a threat to human health. Although probiotics can detoxify HMs in animals, their effectiveness and mechanism of action in humans have not been studied well. Therefore, we conducted this randomized, double-blind, controlled trial on 152 occupational workers from the metal industry, an at-risk human population, to explore the effectiveness of probiotic yogurt in reducing HM levels. Participants were randomly assigned to two groups: one consumed probiotic yogurt containing the HM-resistant strain Pediococcus acidilactici GR-1 and the other consumed conventional yogurt for 12 weeks. Analysis of metal contents in the blood revealed that the consumption of probiotic yogurt resulted in a higher and faster decrease in copper (34.45%) and nickel (38.34%) levels in the blood than the consumption of conventional yogurt (16.41% and 27.57%, respectively). Metagenomic and metabolomic studies identified a close correlation between gut microbiota (GM) and host metabolism. Significantly enriched members of Blautia and Bifidobacterium correlated positively with the antioxidant capacities of GM and host. Further murine experiments confirmed the essential role of GM and protective effect of GR-1 on the antioxidative role of the intestine against copper. Thus, the use of probiotic yogurt may be an effective and affordable approach for combating toxic metal exposure through the protection of indigenous GM in humans. ClinicalTrials.gov identifier: ChiCTR2100053222

Antimicrobial peptides (AMP) are small proteins that play critical roles in host defense against microbe invasion. Many AMPs disrupt the cellular membrane of microbe, while the mechanism of action of AMPs can be very sophisticated. Solid-state NMR (SSNMR) technique is powerful in characterizing the mechanism of AMPs in vivo and in vitro. This review summarizes the recent advance of SSNMR technique in AMP mechanisms characterization. We highlight the sample preparation approaches, the SSNMR spectroscopic methods, and a number of outstanding examples of AMP mechanisms elucidated via SSNMR spectroscopy.

Nodulin 26-like intrinsic proteins (NIPs) are a family of channel-forming transmembrane proteins that function in the transport of water and other small molecules. Some NIPs can mediate silicon transport across plasma membranes and lead to silicon accumulation in plants, which is beneficial for the growth and development of plants. Cucumber is one of the most widely consumed vegetables; however, the functions of NIPs in this crop are still largely unknown. Here, we report the functional characteristics of CsNIP2;2. It was found that CsNIP2;2 is a tandem repeat of CsNIP2;1, which had been demonstrated to be a silicon influx transporter gene. CsNIP2;2 has a selectivity filter composed of cysteine, serine, glycine and arginine (CSGR), which is different from all previously characterized silicon influx transporters in higher plants at the second helix position. Xenopus laevis oocytes injected with CsNIP2;2 cRNA demonstrated a higher uptake of silicon than the control, and the uptake remained unchanged under low temperature. CsNIP2;2 was found to be expressed in the root, stem, lamina and petiole, and exogenous silicon treatment decreased its expression in the stem but not in other tissues. Transient expression of CsNIP2;2-eGFP fusion sequence in onion epidermal cells showed that CsNIP2;2 was localized to the cell nucleus, plasma membrane and an unknown structure inside the cell. The results suggest that CsNIP2;2 is a silicon influx transporter in cucumber, and its subcellular localization and the selectivity filter are different from those of the previously characterized silicon influx transporters in other plants. These findings may be helpful for understanding the functions of NIPs in cucumber plants.

Abstract Circular RNAs (circRNAs) belong to an abundant category of non-coding RNAs that are stable and specific, and thus have great potential in cancer treatment. However, little is known about the role of circRNAs during radiotherapy in lung adenocarcinoma (LUAD). Here, we established the expression profiles of 1,875 dysregulated circRNAs in non-irradiated and irradiated A549 cells and identified circNEIL3 as a significantly downregulated circRNA in A549 cells treated with 0, 2, or 4 Gy of radiation, respectively. Functional assays demonstrated that circNEIL3 knockdown promoted radiation-induced cell pyroptosis, whereas circNEIL3 overexpression had the opposite effects. Importantly, the effects of circNEIL3 overexpression on inhibiting pyroptosis were reversed by PIF1 knockdown. Mechanistically, circNEIL3-mediated pyroptosis was achieved through directly binding to miR-1184 as a sponge, thereby releasing the inhibition of miR-1184 on PIF1, which ultimately induces DNA damage and triggers AIM2 inflammasome activation. In vivo, circNEIL3 knockdown significantly enhanced the efficacy of radiotherapy as evidenced by decreases in tumor volume and weight. Collectively, the circNEIL3/miR-1184/PIF1 axis that mediate pyroptosis induction may be a novel, promising therapeutic strategy for the clinical treatment of lung cancer.

Tomato (Solanumlycopersicum) is a model plant for research on fruit development and stress response, in which gene expression analysis is frequently conducted. Quantitative PCR (qPCR) is a widely used technique for gene expression analysis, and the selection of reference genes may affect the accuracy of results and even conclusions. Although there have been some frequently used reference genes in tomato, it has been shown that the expressions of some of these genes are not constant in different tissues and environmental conditions. Moreover, little information on genomic identification of reference genes is available in tomato. Here, we mined the publicly available transcriptional sequencing data and screened out fifteen candidate reference genes, and the expression stability of these candidate genes and seven traditionally used ones were evaluated under stress and hormone treatment. The results showed that over half of the selected candidate references were housekeeping genes in tomato cells. Among the candidate reference genes and the traditionally used ones, the most stably expressed genes varied under different treatments, and most of these genes were recommended as preferred reference genes at least once except Solyc04g009030 and Solyc07g066610, two traditionally used reference genes. This study provides some novel reference genes in tomato, and the preferred reference genes under different environmental stimuli, which may be useful for future research. Our study suggests that excavating stably expressed genes from transcriptome sequencing data is a reliable approach to screening reference genes for qPCR analysis.

Background: Sarcopenia is an aging syndrome that increases the risks of various adverse outcomes, including falls, fractures, physical disability, and death. Sarcopenia can be diagnosed through medical images-based body part analysis, which requires laborious and time-consuming outlining of irregular contours of abdominal body parts. Therefore, it is critical to develop an efficient computational method for automatically segmenting body parts and predicting diseases.Methods: In this study, we designed an Artificial Intelligence Body Part Measure System (AIBMS) based on deep learning to automate body parts segmentation from abdominal CT scans and quantification of body part areas and volumes. The system was developed using three network models, including SEG-NET, U-NET, and Attention U-NET, and trained on abdominal CT plain scan data.Results: This segmentation model was evaluated using multi-device developmental and independent test datasets and demonstrated a high level of accuracy with over 0.9 DSC score in segment body parts. Based on the characteristics of the three network models, we gave recommendations for the appropriate model selection in various clinical scenarios. We constructed a sarcopenia classification model based on cutoff values (Auto SMI model), which demonstrated high accuracy in predicting sarcopenia with an AUC of 0.874. We used Youden index to optimize the Auto SMI model and found a better threshold of 40.69.Conclusion: We developed an AI system to segment body parts in abdominal CT images and constructed a model based on cutoff value to achieve the prediction of sarcopenia with high accuracy.

With the continuous development of industry, an increasing number of nanomaterials are widely used. CdTe-QDs is a nanomaterial with good optical properties, but its release into the natural environment may pose a potential threat. The toxicity of nanoparticles in plants is beginning to be questioned, and the effect on phytotoxicity is unclear. In this study, we simulated air pollution and soil pollution (CdTe-QDs concentrations of 0, 0.2, 0.4, 0.8 mmol/L) by spraying and watering the seedlings, respectively. We determined the transport pathways of CdTe-QDs in Arabidopsis thaliana and their effects on plant reproductive growth. Spraying CdTe-QDs concentration >0.4 mmol/L significantly inhibited the formation of fruit and decreased the number of seeds. Observation with a laser confocal scanning microscope revealed that CdTe-QDs were mainly transported in plants through the vascular bundle, and spraying increased their accumulation in the anthers and ovaries. The expression level of genes associated with Cd stress was analyzed through RT-qPCR. CdTe-QDs significantly increased the expression levels of 10 oxidative stress-related genes and significantly decreased the expression levels of four cell-proliferation-related genes. Our results reveal for the first time the transport of CdTe-QDs in Arabidopsis flowers and demonstrate that QDs can cause abnormal pollen morphology, form defects of pollen vitality, and inhibit pollen tube growth in Arabidopsis through oxidative damage. These phenomena ultimately lead to the inability of Arabidopsis to complete the normal fertilization process and affect the reproductive growth of the plant.

The purpose of this article is to explore the role of gut microbiota in the pathogenesis and treatment of bipolar disorder， so as to provide a new perspective for the clinical diagnosis and treatment of bipolar disorder. The pathogenesis of bipolar disorder remains unclear， while research has identified multiple pathways by which gut microbiota may be involved in the development of bipolar disorder， making it a potential new target for the treatment of bipolar disorder. Therefore， this article reviews recent research advances on the role of gut microbiota in the pathogenesis and treatment of bipolar disorder， thus providing a reference for further research on bipolar disorder.

Abstract Background Nowadays, because of the increasing incidence, the prevention and control of myopia has become an urgent issue. In China, auricular acupressure has been commonly used in the clinical treatment of myopia in children, but the exact effectiveness remains unproven. The purpose of this trial is to observe the efficacy of auricular acupressure in myopia prevention and control, as well as its effect on the choroidal and retinal thickness. Method/design A total of 480 subjects at 8–9 years old will be randomized in a 1:1 ratio to an intervention group versus a control group. The intervention group will receive auricular acupressure for 12 months, while the control group will be taken as a blank control. The primary and secondary outcomes will be measured at baseline, and again at 3, 6, 9, and 12 months after recruitment. The myopia incidence (spherical equivalent ≤ − 0.50 D) and the mean change of spherical equivalent will be taken as the primary variables; the secondary outcome measures include axial length, uncorrected visual acuity, and choroidal and retinal thickness. Discussion This trial aims to evaluate the effectiveness of auricular acupressure for myopia prevention and control with objective evidence and to preliminarily explore the plausible mechanism and provide reference for adopting this approach to retard the onset and control the progression of myopia. Trial registration Chinese Clinical Trial Registry ChiCTR2000038456 . Registered on September 23, 2020.

As a zone of interaction between land and sea, coastal zones are important carriers of the marine economy, and they are the focal point for strategies related to strengthening a country by means of the sea. As the coastal zones are where land and sea are most closely linked, they become a strategic area for achieving sustainable expansion of the blue economic space. Coastal zones have some capacity to cope with and recover from the adverse effects of ecological pressure, which is the coastal zone ecosystem vulnerability. However, given the vulnerability of coastal zone ecosystems and the existence of considerable ecological pressure, it is necessary to systematically assess coastal zones’ vulnerability and propose targeted countermeasures. First of all, this paper uses normative research methods and the methods that combine quantitative research with qualitative research to investigate the assessment of coastal zone ecosystem vulnerability and propose solutions for related governance. Second, based on an analysis of the shortcomings of existing methods, this study constructed an index system based on “object–pressure–endurance–resilience” (O-P-E-R) to assess coastal zone ecosystem vulnerability. O-P-E-R takes into account the triad of nature–society–culture and systematically defines ecosystem vulnerability. In the meantime, a combined weight calculation method that considers subjective and objective weights was proposed based on an improved group analytic hierarchy process (GAHP) method and the entropy weight method. Further, based on the standardization and normalization of indicator values, a method and scale for assessing coastal zone ecosystem vulnerability were proposed based on an improved matter-element model. In conclusion, the research has established a coastal zone ecosystem vulnerability assessment system that not only expand the safety management of coastal zone ecosystems but also provide a theoretical basis for governments to formulate related policies.

Keloids, benign fibroproliferative cutaneous lesions, are characterized by abnormal growth and reprogramming of the metabolism of keloid fibroblasts (KFb). However, the underlying mechanisms of this kind of metabolic abnormality have not been identified. Our study aimed to investigate the molecules involved in aerobic glycolysis and its exact regulatory mechanisms in KFb. We discovered that polypyrimidine tract binding (PTB) was significantly upregulated in keloid tissues. siRNA silencing of PTB decreased the mRNA levels and protein expression levels of key glycolytic enzymes and corrected the dysregulation of glucose uptake and lactate production. In addition, mechanistic studies demonstrated that PTB promoted a change from pyruvate kinase muscle 1 (PKM1) to PKM2, and silencing PKM2 substantially reduced the PTB-induced increase in the flow of glycolysis. Moreover, PTB and PKM2 could also regulate the key enzymes in the tricarboxylic acid (TCA) cycle. Assays of cell function demonstrated that PTB promoted the proliferation and migration of KFb in vitro, and this phenomenon could be interrupted by PKM2 silencing. In conclusion, our findings indicate that PTB regulates aerobic glycolysis and the cell functions of KFb via alternative splicing of PKM.

Neuroinflammation plays an important role in the pathogenesis of many central nervous system diseases. Here, we investigated the effect of an anti-cancer compound RRx-001 on neuroinflammation and its possible new applications. BV2 cells and primary microglia cells were used to evaluate the role of RRx-001 in LPS-induced microglial activation and inflammatory response in vitro. And, we found that the increase in the synthesis and release of cytokines and the up-regulation of pro-inflammatory factors in LPS-treated microglial cells were significantly reduced by RRx-001 pretreatment. As the most classical inflammatory pathways, NF-κB and MAPK signaling pathways were activated by LPS, but were inhibited by RRx-001. Transcription of NLRP3 was also reduced by RRx-001. In addition, LPS induced oxidative stress by increasing the expression of Nox mediated by transcription factors NF-κB and AP-1, while RRx-001 pretreatment ameliorated Nox-mediated oxidative stress. LPS-induced activation of TAK1, an upstream regulator of NF-κB and MAPK pathways, was significantly inhibited by RRx-001 pretreatment, whereas recruitment of MyD88 to TLR4 was not affected by RRx-001. LPS-primed BV2 condition medium induced injury of primary neurons, and this effect was inhibited by RRx-001. Furthermore, we established a neuroinflammatory mouse model by stereotactic injection of LPS into the substantia nigra pars compacta (SNpc), and RRx-001 dose-dependently reduced LPS-induced microglial activation and loss of TH + neurons in the midbrain. In conclusion, the current study found that RRx-001 suppressed microglia activation and neuroinflammation through targeting TAK1, and may be a candidate for the treatment of neuroinflammation-related brain diseases.

The influence of different NaCl concentrations (2.5, 5, 7.5 and 10% (w/w)) on the mass transfer kinetics of tuna during brining process with and without ultrasound assistance was evaluated. Results showed that an increase in NaCl concentration and the application of ultrasound accelerated the salt diffusion in the tuna muscle, and the highest yield was obtained in 5% brine concentration. Moreover, the kinetics parameters were significantly affected by the NaCl concentration and ultrasound application during brining. The values of the mass transfer kinetics parameters (k1, k2) for total and water weight changes decreased as NaCl concentration increased with and without ultrasound assistance during brining. In contrast, the higher the NaCl concentration, the higher the value of the salting kinetics parameters for salt weight changes. The application of ultrasound enhanced the salt effective diffusion coefficient (De) from 402.8% to 653.21% during the brining process, and the highest De was also found at 5% brine concentration. The application of ultrasound can improve the uniformity of salt distribution, enhance water holding capacity, reduce hardness and chewiness, but have no significant effect on color of tuna muscle.

Abstract Specific roles of gut microbes in COVID‐19 progression are critical. However, the circumstantial mechanism remains elusive. In this study, shotgun metagenomic or metatranscriptomic sequencing was performed on fecal samples collected from 13 COVID‐19 patients and controls. We analyzed the structure of gut microbiota, identified the characteristic bacteria, and selected biomarkers. Further, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotations were employed to correlate the taxon alterations and corresponding functions. The gut microbiota of COVID‐19 patients was characterized by the enrichment of opportunistic pathogens and depletion of commensals. The abundance of Bacteroides spp. displayed an inverse relationship with COVID‐19 severity, whereas Actinomyces oris, Escherichia coli, and Streptococcus parasanguini were positively correlated with disease severity. The genes encoding oxidoreductase were significantly enriched in gut microbiome of COVID‐19 group. KEGG annotation indicated that the expression of ABC transporter was upregulated, while the synthesis pathway of butyrate was aberrantly reduced. Furthermore, increased metabolism of lipopolysaccharide, polyketide sugar, sphingolipids, and neutral amino acids were found. These results suggested the gut microbiome of COVID‐19 patients was in a state of oxidative stress. Healthy gut microbiota may enhance antiviral defenses via butyrate metabolism, whereas the accumulation of opportunistic and inflammatory bacteria may exacerbate COVID‐19 progression.

The emission allocation strategies of global scenarios do not specify the potential benefits from extra climate mitigation efforts. Here the authors show that compared to the current Nationally Distributed Contributions, the proposed self-preservation strategy might generate 126–616 trillion dollars of additional benefits by 2100.

Procambarus clarkii (crayfish) accumulates a high concentration of Arsenic (As) from the aquatic environment and causes considerable human health risks. In this study, Limosilactobacillus fermentum GR-3 strain was isolated from “Jiangshui” and applied for As(III) adsorption and antioxidant abilities. Strain GR-3 removed 50.67% of 50 mg/L As(III) and exhibited the high antioxidant potential of DPPH (1,1-Diphenyl-2-picrylhydrazyl) (87.63%) and hydroxyl radical (74.51%) scavenging rate in vitro. P. clarkii was feed with strain GR-3, the results showed that As(III) concentration reduced, and residual level in hepatopancreas was decreased by 36%, compared to As(III)-exposed group (control). Gut microbial sequencing showed that strain GR-3 restores gut microbiota dysbiosis caused by As(III) exposure. Further application in the field scale was performed and revealed a decrease in As(III) accumulation and increasing 50% aquaculture production of the total output. In summary, feed-additive probiotic is recommended as a novel strategy to minimize aquaculture foods toxicity and safe human health.

Dental caries, particularly secondary caries, which is the main contributor to dental repair failure, has been the subject of extensive research due to its biofilm-mediated, sugar-driven, multifactorial, and dynamic characteristics. The clinical utility of restorations is improved by cleaning bacteria nearby and remineralizing marginal crevices. In this study, a novel multifunctional dental resin composite (DRC) composed of Sr-N-co-doped titanium dioxide (Sr-N-TiO2) nanoparticles and nano-hydroxyapatite (n-HA) reinforcing fillers with improved antibacterial and mineralization properties is proposed. The experimental results showed that the anatase-phase Sr-N-TiO2 nanoparticles were synthesized successfully. After this, the curing depth (CD) of the DRC was measured from 4.36 ± 0.18 mm to 5.10 ± 0.19 mm, which met the clinical treatment needs. The maximum antibacterial rate against Streptococcus mutans (S. mutans) was 98.96%, showing significant inhibition effects (p < 0.0001), which was experimentally verified to be derived from reactive oxygen species (ROS). Meanwhile, the resin exhibited excellent self-remineralization behavior in an SBF solution, and the molar ratio of Ca/P was close to that of HA. Moreover, the relative growth rate (RGR) of mouse fibroblast L929 indicated a high biocompatibility, with the cytotoxicity level being 0 or I. Therefore, our research provides a suitable approach for improving the antibacterial and mineralization properties of DRCs.

Carbon dots (CDs) possess considerable potentials in fields like biomarker and cell imaging due to its good fluorescence properties. Nevertheless, the molecular mechanism concerning influences of CDs on plant growth still remains unknown. In this study, the subcellular localization of CDs in Arabidopsis and the molecular mechanism of CDs toxicity to plants were investigated. Results demonstrate that CDs tend to accumulate in meristematic nucleus of root tips. CDs can inhibit growth of meristem zone of primary root (PR) of Arabidopsis seedlings significantly. The transcription level of auxin biosynthesis related genes decreases and the abundance of auxin efflux carriers PIN1 and PIN2 declines after 40 mg/L CDs treatment, thus lowering the auxin level in root tips. Moreover, CDs weaken activity of cell division in meristem zone by disturbing expressions of DNA damage repair genes and cell cycle regulation genes, thus enabling to inhibit growth of the meristem zone. To sum up, CDs inhibit growth of Arabidopsis seedlings through above pathways. These results provide useful information to elaborate potential toxicity mechanism of CDs on terrestrial plants.

Abstract Background Macroautophagy (hereafter autophagy) is a tightly regulated process that delivers cellular components to lysosomes for degradation. Damage-regulated autophagy modulator 1 (DRAM1) induces autophagy and is necessary for p53-mediated apoptosis. However, the signalling pathways regulated by DRAM1 are not fully understood. Methods HEK293T cells were transfected with FLAG-DRAM1 plasmid. Autophagic proteins (LC3 and p62), phosphorylated p53 and the phosphorylated proteins of the class I PI3K-Akt-mTOR-ribosomal protein S6 (rpS6) signalling pathway were detected with Western blot analysis. Cellular distribution of DRAM1 was determined with immunostaining. DRAM1 was knocked down in HEK293T cells using siRNA oligos which is confirmed by quantitative RT-PCR. Cells were serum starved for 18 h after overexpression or knockdown of DRAM1 to decrease the rpS6 activity to the basal level, and then the cells were stimulated with insulin growth factor, epidermal growth factor or serum. rpS6 phosphorylation and rpS6 were detected with Western blotting. Similarly, after overexpression or knockdown of DRAM1, phosphorylation of IGF-1Rβ and IGF-1R were examined with Western blotting. Cell viability was determined with CCK-8 assay and colony formation assay. Finally, human cancer cells Hela, SW480, and HCT116 were transfected with the FLAG-DRAM1 plasmid and phosphorylated rpS6 and rpS6 were detected with Western blot analysis. Results DRAM1 induced autophagy and inhibited rpS6 phosphorylation in an mTORC1-dependent manner in HEK293T cells. DRAM1 didn’t affect the phosphorylated and total levels of p53. Furthermore, DRAM1 inhibited the activation of the PI3K-Akt pathway stimulated with growth factors or serum. DRAM1 was localized at the plasma membrane and regulate the phosphorylation of IGF-1 receptor. DRAM1 decreased cell viability and colony numbers upon serum starvation. Additionally, DRAM1 inhibited rpS6 phosphorylation in several human cancer cells. Conclusions Here we provided evidence that DRAM1 inhibited rpS6 phosphorylation in multiple cell types. DRAM1 inhibited the phosphorylation of Akt and the activation of Akt-rpS6 pathway stimulated with growth factors and serum. Furthermore, DRAM1 regulated the activation of IGF-1 receptor. Thus, our results identify that the class I PI3K-Akt-rpS6 pathway is regulated by DRAM1 and may provide new insight into the potential role of DRAM1 in human cancers.

Abstract Anaplasma species are tick-transmitted obligate intracellular bacteria that infect many wild and domestic animals and humans. The prevalence of Anaplasma spp. in ixodid ticks of Qinghai Province is poorly understood. In this study, a total of 1104 questing adult ticks were investigated for the infection of Anaplasma species. As a result, we demonstrated the total infection rates of 3.1, 11.1, 5.6, and 4.5% for A. phagocytophilum, A. bovis, A. ovis and A. capra, respectively. All of the tick samples were negative for A. marginale. The positive rates of A. phagocytophilum, A. ovis and A. capra in different tick species were significantly different. The positive rates of A. capra and A. bovis in the male ticks were significantly higher than that in the female ticks. Sequence analysis of A. ovis showed 99.5–100% identity to the previous reported isolates. The sequences of A. phagocytophilum had 100% identity to strains Ap-SHX21, JC3–3 and ZAM dog-181 from sheep, Mongolian gazelles, and dogs. Two genotypes of A. capra were found based on 16S rRNA, citrate synthase (gltA) gene and heat shock protein (groEL) gene analysis. In conclusion, A. bovis, A. ovis, A. phagocytophilum, and A. capra were present in the ticks in Qinghai Province. Anaplasma infection is associated with tick species, gender and distribution. These data will be helpful for understanding prevalence status of Anaplasma infections in ticks in Qinghai-Tibet Plateau.

Crohn's disease is a chronic inflammatory bowel disease and the NLRP3 inflammasome plays an important role in Crohn's disease. Previous studies have shown that Herb-partitioned moxibustion treating (at Qihai (CV 6) and Tianshu (ST 25)) prevented the excessive activation of the NLRP3 inflammasome and repaired damaged colonic mucosa in Crohn's disease. However, the mechanism by which Herb-partitioned moxibustion (at CV 6 and ST 25) regulates NLRP3 remains unclear. In this study, we treated Crohn's disease rats with herb-partitioned moxibustion (at CV 6 and ST 25) to investigate the mechanism by which Herb-partitioned moxibustion regulates the colonic NLRP3 inflammasome by observing colon length, the colon macroscopic damage indexes, and the expression of ATP, P2X7R, Pannexin-1, NF-κBp65, NLRP3, ASC, caspase-1, IL-1β and IL-18 in the colon in Crohn's disease. Here, this study shows that herb-partitioned moxibustion (at CV 6 and ST 25) can reduce colon macroscopic damage indexes and colon histopathological scores, alleviate colon shortening and block the abnormal activation of the NLRP3 inflammasome by inhibiting the ATP content and the expression of P2X7R, Pannexin-1 and NF-κBp65, thereby reducing the release of the downstream inflammatory cytokine IL-1β and ultimately suppressing colonic inflammation in Crohn's disease rats. This study for the first time identifies the mechanism by which herb-partitioned moxibustion (at CV 6 and ST 25) may inhibit the abnormal activation of the NLRP3 inflammasome by inhibiting the P2X7R-Pannexin-1 signaling pathway in Crohn's disease rats.

In order to investigate the dynamic characteristics of blunt aircraft mounted with aerospikes and aerodisks in large-amplitude force-pitching, the Roe spatial scheme and the lower-upper symmetric Gauss-Seidel (LU-SGS) method with dual time step are employed for discretization of unsteady Navier-Stokes (N-S) equations. A parametric investigation on the flow fields is conducted by altering the pitching period, aerospike length, and aerodisk diameter consequently via a variable-controlling procedure. Dynamic characteristics of aerodynamic drag as well as the visualization of unsteady flow fields are achieved, and the results show that the aerodynamics of hypersonic aircraft under the condition of large-amplitude force-pitching vibration have hysteresis characteristics affected by periods of force-pitching vibration. In addition, when changing aerospike length and aerodisk diameter, the variation tendency of drag reduction efficiency is determined by the pitching angle of the oscillation process.

Background. Use of 0.01% atropine eye drops (0.01% A) is one of the most common treatments for myopia control for children in Asia. Auricular acupoint stimulation (AAS) was reported to enhance the effect of higher-concentration atropine (0.25%, 0.125%) on myopia control. This study was designed to compare the effect of 0.01% A combined with AAS and 0.01% A alone on myopia progression and choroidal thickness in children. Methods. A total of 104 children were stratified by age and randomly assigned at 1 : 1 to receive 0.01% A or 0.01% A + AAS treatment for 6 months. Repeated measurements of cycloplegic spherical equivalent (SE) autorefraction, axial length (AL), and choroidal thickness were performed at baseline, 1 month, 3 months, and 6 months. Results. The adjusted mean SE change over the 6 months was −0.38 ± 0.04 D in the 0.01% A group (n = 50) and −0.25 ± 0.04 D in the 0.01% A + AAS group (n = 50), demonstrating a significant between-group difference (P = 0.02). There was no statistically significant difference in the change of AL and choroidal thickness between the two groups (both P > 0.05). Conclusions. Adjunctive AAS compared with 0.01% A monotherapy slowed myopic progression in Chinese children by a statistically small amount, but had no effect on axial elongation and choroidal thickness during this 6-month observation. The trial is registered with ChiCTR1900021316.

Recent studies into the beneficial effects of fermented foods have shown that this class of foods are effective in managing hyperuricemia and gout. In this study, the uric acid (UA) degradation ability of Limosilactobacillus fermentum JL-3 strain, isolated from “Jiangshui” (a fermented Chinese food), was investigated. In vitro results showed that JL-3 strain exhibited high degradation capacity and selectivity toward UA. After oral administration to mice for 15 days, JL-3 colonization was continuously detected in the feces of mice. The UA level in urine of mice fed with JL-3 was similar with the control group mice. And the serum UA level of the former was significantly lower (31.3%) than in the control, further confirmed the UA-lowering effect of JL-3 strain. Limosilactobacillus fermentum JL-3 strain also restored some of the inflammatory markers and oxidative stress indicators (IL-1β, MDA, CRE, blood urea nitrogen) related to hyperuricemia, while the gut microbial diversity results showed that JL-3 could regulate gut microbiota dysbiosis caused by hyperuricemia. Therefore, the probiotic Limosilactobacillus fermentum JL-3 strain is effective in lowering UA levels in mice and could be used as a therapeutic adjunct agent in treating hyperuricemia.

Salmon (Salmo salar) is a precious fish with high nutritional value, which is perishable when subjected to improper tempering processes before consumption. In traditional air and water tempering, the medium temperature of 10 °C is commonly used to guarantee a reasonable tempering time and product quality. Radio frequency tempering (RT) is a dielectric heating method, which has the advantage of uniform heating to ensure meat quality. The effects of radio frequency tempering (RT, 40.68 MHz, 400 W), water tempering (WT + 10 °C, 10 ± 0.5 °C), and air tempering (AT + 10 °C, 10 ± 1 °C) on the physiochemical properties of salmon fillets were investigated in this study. The quality of salmon fillets was evaluated in terms of drip loss, cooking loss, color, water migration and texture properties. Results showed that all tempering methods affected salmon fillet quality. The tempering times of WT + 10 °C and AT + 10 °C were 3.0 and 12.8 times longer than that of RT, respectively. AT + 10 °C produced the most uniform temperature distribution, followed by WT + 10 °C and RT. The amount of immobile water shifting to free water after WT + 10 °C was higher than that of RT and AT + 10 °C, which was in consistent with the drip and cooking loss. The spaces between the intercellular fibers increased significantly after WT + 10 °C compared to those of RT and AT + 10 °C. The results demonstrated that RT was an alternative novel salmon tempering method, which was fast and relatively uniform with a high quality retention rate. It could be applied to frozen salmon fillets after receiving from overseas catches, which need temperature elevation for further cutting or consumption.

Introduction Intra-articular (IA) injection of hyaluronic acid (HA) and corticosteroid (CS) is a common treatment for osteoarthritis (OA) of the knee. As a drug treatment for patients with depression, duloxetine has been shown in many studies to effectively relieve the pain of OA and improve function of the knee joint. However, evidence regarding the efficacy of IA injection of HA+CS combined with duloxetine for pain management in patients with OA of the knee is lacking. The aim of this study was to test the hypothesis that IA injection of HA+CS combined with duloxetine could achieve pain management superior to that of IA injection of HA+CS alone in patients experiencing knee OA pain.Methods This study will adopt a prospective, randomised, open-label blind endpoint study design. In total, 150 patients with OA of the knee will be enrolled in the study. The participants will be randomly allocated to receive either a single IA injection of HA+CS combined with duloxetine or a single IA injection of HA+CS alone, and both groups will complete a 24-week follow-up to assess pain and functional improvements. The primary outcome measure is the change in the weekly mean of the 24 hours average pain scores from baseline to the end of 24 weeks in patients with OA of the knee, and the secondary outcomes include the response to treatment, changes from baseline in the brief pain inventory, improvement in the Western Ontario and McMaster Universities Osteoarthritis index scores, patient global impression of improvement scale, Hospital Anxiety and Depression Scale and adverse events during the 24-week follow-up. The data will be analysed by the intention-to-treat principle.Ethics approval and dissemination This study was approved by the institutional ethics committee of the Beijing Tiantan Hospital (approval number: KY 2019-086-02). The results of the study will be published in peer-reviewed journals, and the findings will be presented at scientific meetings.Trial registration number ClinicalTrials.gov Identifier: NCT04117893; Pre-results.

Background: Little is known about the association between ambient temperature and cause-specific mental disorders, especially in subtropical areas. Objective: To investigate the effect of ambient temperature on mental disorders in subtropical cities. Method: Daily morbidity data for mental disorders in three Chinese cities (Shenzhen, Zhaoqing, and Huizhou) were collected from medical record systems of local psychiatric specialist hospitals, covering patients of all ages. Case-crossover design combined with a distributed lag nonlinear model (DLNM) was used to assess the nonlinear and delayed effects of temperatures on five specific mental disorders (affective disorders, anxiety, depressive disorders, schizophrenia, and organic mental disorders), with analyses stratified by gender and age. The temperature of minimum effect was used as the reference value to calculate estimates. Results: We observed inversed J-shaped exposure-response curves between temperature and mental morbidity and observed that low temperatures had a significant and prolonged effect on most types of mental disorders in the three cities. For example, the effect of the cold (2.5th percentile) on anxiety was consistently observed in the three cities with an odds ratio (OR) of 1.29 (95% CI: 1.06–1.57) in Zhaoqing, 1.26 (95% CI: 1.18–1.34) in Shenzhen, and 1.45 (95% CI: 1.17–1.81) in Huizhou. Low temperature was also associated with an increased risk of depressive disorders and schizophrenia. For the high temperature exposure (97.5th percentile), we only observed a significant, harmful effect on anxiety [OR = 1.30 (95% CI: 1.08, 1.58) in Shenzhen, OR = 1.16 (95% CI: 1.00, 1.34) in Zhaoqing], affective disorders [OR = 1.32 (95% CI: 1.08, 1.62) in Shenzhen], and schizophrenia [OR = 1.24 (95% CI: 1.03, 1.48) in Zhaoqing, OR = 1.03 (95% CI: 1.00, 1.06) in Huizhou]. Conclusions: Our study suggests that both low and high temperatures might be important drivers of morbidity from mental disorders, and low temperature may have a more general and wide-spread effect on this cause-specific morbidity than high temperature.

Background: Heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 is an important RNA-binding protein that affects the RNA processing, splicing, transport and stability of many genes. hnRNPA2/B1 is expressed during proliferation and metastasis of various cancer types and promotes such processes. However, the precise role and mechanism of hnRNPA2/B1 in breast cancer remain unclear. Methods: The association of hnRNPA2/B1 with breast cancer metastasis was assessed using tissue chips, mouse models and publicly available data. The role and mechanism of hnRNPA2/B1 in breast cancer metastasis were studied in cell lines and mouse models. Findings: In contrast to other cancer research findings, hnRNPA2/B1 expression was negatively correlated with breast cancer metastasis. hnRNPA2/B1 inhibited MDA-MB-231 triple-negative breast cancer (TNBC) cell metastasis in vitro and in vivo. hnRNPA2/B1 knockout activated ERK-MAPK/Twist and GR-beta/TCF4 pathways but inhibited STAT3 and WNT/TCF4 signalling pathways. Profilin 2 (PFN2) promoted breast cancer cell migration and invasion, whereas hnRNPA2/B1 bound directly to the UAGGG locus in the 3′-untranslated region of PFN2 mRNA and reduced the stability of PFN2 mRNA. Interpretation: Our data supported the role of hnRNPA2/B1 in tumour metastasis risk and survival prediction in patients with breast cancer. The inhibitory role of hnRNPA2/B1 in metastasis was a balance of downstream multiple genes and signalling pathways. PFN2 downregulation by hnRNPA2/B1 might partly explain the inhibitory mechanism of hnRNPA2/B1 in breast cancer metastasis. Therefore, hnRNPA2/B1 might be used as a new prognostic biomarker and valuable molecular target for breast cancer treatments. Keywords: Heterogeneous nuclear ribonucleoprotein A2/B1, Breast cancer metastasis, Epithelial–mesenchymal transition, Profilin 2

Background/Aims: Recent studies have reported the importance of tubulin alpha 4b (TUBA4B), a long non-coding RNA, in the development of several cancers; however, studies on its clinical significance are rare. In the present meta-analysis, we investigated whether TUBA4B can be used as a prognostic biomarker in human cancers. Methods: A comprehensive search was performed in PubMed, Embase, Web of Science, and the Gene Expression Omnibus databases. Hazard ratios from individual studies were calculated and pooled using a random-effects or fix-effects model. The pooled hazard ratio (HR) with 95% confidence interval (CI) was used to evaluate the value of TUBA4B. The expression of TUBA4B was evaluated in lung cancer tissue arrays by fluorescence in situ hybridization assay. Additionally, a sensitivity analysis and Begg’s test were conducted. Results: We found that TUBA4B was significantly correlated with overall survival (OS) (HR = 1.33, 95% CI: 1.16–1.52, P=0.000), disease-free survival (DFS; HR = 1.25, 95% CI: 1.06–1.48, P=0.007), and recurrence-free survival (RFS; HR = 1.42, 95% CI: 1.26–1.60, P=0.000). In addition, TUBA4B was a risk factor for lung cancer (HR = 1.24, 95% CI: 1.03–1.49, P=0.021), colon cancer (HR = 1.67, 95% CI: 1.02–2.74, P=0.042), breast cancer (HR = 1.52, 95% CI: 1.10–2.12, P=0.012), and ovarian cancer (HR = 1.67, 95% CI: 1.18–2.36, P=0.004). Moreover, LncRNA-TUBA4B was significantly lower expression in tumor tissues than normal lung tissues (P< 0.001). The expression of lncRNA-TUBA4B was decreased with the progression of lung cancer stage. A subgroup meta-analysis based on data resource, sample size, region, patient numbers, and tumor type was further performed. Our studies revealed that tumor tissues with low levels of TUBA4B was significantly associated with short OS, DFS, and RFS in cancer patients. Conclusion: The present findings suggest that TUBA4B can be a novel biomarker for the prognosis of various cancers.

Abstract Background To compare the safety and efficacy of topical anesthesia versus retrobulbar anesthesia in 27-gauge pars plana vitrectomy (PPV) for vitreous floaters. Methods 30 patients with vitreous floaters were randomized into Group T (topical anesthesia, proparacaine eye drop) and Group R (retrobulbar anesthesia), and underwent 27-gauge PPV. A 5-point visual analogue pain scale (VAPS) was used to assess patients’ pain experience of anesthesia and surgery procedure (during surgery, 2 h and 1 day after surgery). Results The VAPS of anesthesia procedure was 1.27 ± 0.59 for patients in Group R, while it was all 0 for patients in Group T (p

The flow past a cylinder is a classical problem in flow physics. In a certain range of Reynolds number, there will be Karman vortex street phenomenon in the wake of a cylinder, which will greatly increase the pressure drag of the cylinder. By controlling the vortex shedding phenomenon, drag reduction of the cylinder could be effectively realized. In this paper, a NACA0012 airfoil with pitching oscillation is placed downstream of the cylinder. Based on the tight coupling method, kinematics equations and Navier–Stokes equations in the arbitrary Lagrangian–Eulerian form are solved. Firstly, the effect of airfoil oscillation period and the distance between airfoil leading edge and cylinder center (x/D) are studied respectively, especially considering the aspects of vortex shedding and drag reduction effect. Besides, the vortex interaction in the flow field around the airfoil and cylinder is analyzed in detail. It is found that the NACA0012 airfoil with pitching oscillation can change the period of vortex shedding. Moreover, it can also increase the drag reduction rate to as high as 50.5%, which presents a certain application prospect in the engineering drag reduction field, e.g., for launch vehicles, ship masts, submarine pipelines, etc.

Abstract Background Anaplasma marginale is an important tick-transmitted rickettsial pathogen of cattle, with worldwide distribution and an important economic impact. The genetic diversity of A. marginale strains has been extensively characterized in different geographical regions throughout the world, while information is limited on studies in China. This study was carried out to determine the prevalence and genetic diversity of A. marginale strains in cattle from ten provinces of China. Methods A total of 557 blood samples from cattle were collected and screened for the occurrence of A. marginale by PCR based on the msp4 gene. The partial msp1a gene containing tandem repeat sequences was further amplified from msp4 positive samples. The Msp1a amino acid repeats were identified, and genetic variation of A. marginale strains was characterized based on the variation in the repeated portion of Msp1a. Results Our results showed that 31.6% of 557 cattle were positive for A. marginale. The infection rates of A. marginale varied considerably from 0 to 96.9% in different sampling regions. Sequence analysis revealed that two msp4 sequence variants of A. marginale exist in cattle. One hundred and three msp1a sequences were obtained and permitted to identify 42 Msp1a tandem repeats, 21 of which were not previously published for A. marginale. Moreover, 61 A. marginale genotypes were identified based on the structure of Msp1a tandem repeats. Conclusions Anaplasma marginale is widely distributed in China and a high prevalence of infection was observed in cattle. The geographical strains of A. marginale were molecularly characterized based on the structure of Msp1a tandem repeats. Forty-two Msp1a tandem repeats and 61 genotypes of A. marginale were identified. This study, for the first time, revealed the genetic diversity of A. marginale strains in cattle in China.

Microtubule organization was compared between the Arabidopsis thaliana TUB-GFP and MBD-GFP mutants. Plant height and primary root length were measured, and microtubule dynamics were examined by confocal laser scanning microscopy after UV-B radiation to reveal changes in microtubules. Damage caused by UV-B was comparable between transgenic lines and wild-type plants, although transgenic lines were more sensitive to UV-B than the wild-type. Spots and depolymerization of microtubules were detected in both TUB-GFP and MBD-GFP plants; however, MBD-GFP showed better adaptation of changes induced by UV-B treatment. These results indicated that UV-B inhibits the growth and development of transgenic lines, and the inhibitory effects might result from changes in microtubules, as determined by comparison between the TUB-GFP and MBD-GFP lines.

Abstract Background Anaplasma ovis is one of the tick-transmitted pathogens of small ruminants. It causes ovine anaplasmosis and widely distributed in the world. In contrast to extensive worldwide genetic diversity of A. marginale and A. phagocytophilum, there are few reports on the classification of A. ovis strains. This study was conducted to investigate the occurrence and characterize A. ovis strains from goats and sheep from 12 provinces in China. Methods The occurrence of A. ovis DNA was tested in 552 goats and sheep, by PCR based on the msp4 gene. Positive samples were used for the amplification of the msp1a gene of A. ovis. The Msp1a amino acid repeats were further identified and used for the characterization of A. ovis strains. Results The results showed that 79 (14.3%) goats and sheep were positive for A. ovis. The infection rates of A. ovis among different study sites ranged from 0 to 100%, and were significantly higher in sheep (26.6%, 45/169) than in goats (8.9%, 34/383) (χ 2 = 21.403, df = 1, P

Abstract The zinc transporter SLC39A4 influences epithelial cell morphology and migration in various cancers; however, its role in regulating cell invasion and chemotherapeutic resistance in human lung cancer is not yet clear. Here, integrated analysis of gene expression in non-small cell lung cancer revealed that SLC39A4 expression is significantly correlated with increased tumour size and regional lymph node spread, as well as shorter overall survival (OS) and disease-free survival (DFS). SLC39A4 silencing by lentivirus-mediated shRNA blocked human lung cancer cell epithelial-mesenchymal transition and metastasis in vitro and in vivo, respectively. Moreover, SLC39A4 knockdown enhanced cancer cell sensitivity to cisplatin-induced death by inhibiting stemness in lung cancer cells. Collectively, these data suggest that SLC39A4 may be a novel therapeutic target and predictive marker of tumour metastasis in non-small cell lung cancer.

Abstract Background Tick-borne diseases currently represent an important issue for global health. A number of emerging tick-transmitted microbes continue to be discovered, and some of these are already identified as the cause of human infections. Over the past two decades, Anaplasma phagocytophilum is considered to be mainly responsible for human anaplasmosis. However, a novel zoonotic pathogen provisionally named “Anaplasma capra” has recently been identified in China. In this study, we did an active surveillance of A. capra in goats and sheep in different geographical regions of China. Methods The presence of A. capra was determined by nested PCR in 547 blood samples collected from goats and sheep from 24 counties distributed in 12 provinces in China. The molecular characterization of A. capra isolates in sheep and goats was achieved based on four conventional genetic markers (16S rRNA, gltA, groEL and msp4 genes). Results Anaplasma capra was identified in 75 of 547 animals, with an overall prevalence of 13.7%. The infection rates in the survey sites ranged from 0 to 78.6%, and were significantly different (P

Purpose: Traditionally acceptable methods of anesthesia for vitrectomy surgery are quite varied. However, each of these methods has its own potential for complications that can range from minor to severe. The surgery procedure of vitrectomy for symptomatic vitreous floaters is much simpler, mainly reflecting in the nonuse of sclera indentation, photocoagulation, and the apparently short surgery duration. The use of 27-gauge cannulae makes the puncture of the sclera minimally invasive. Hence, retrobulbar anesthesia, due to its rare but severe complications, seemed excessive for this kind of surgery. Method: Three cases of 27-gauge, sutureless pars plana vitrectomy for symptomatic vitreous floaters with topical anesthesia are reported. Results: The vitrectomy surgeries were successfully performed with topical anesthesia (proparacaine, 0.5%) without operative or postoperative complications. Furthermore, none of the patients experienced apparent pain during or after the surgery. Conclusion: Topical anesthesia can be considered for 27-guage vitrectomy in patients with symptomatic vitreous floaters.

Purpose: To report a case of Staphylococcus epidermidis endophthalmitis following 27-gauge pars plana vitrectomy for symptomatic vitreous floaters. Methods: The clinical course and imaging findings, including fundus optomap, and spectral domain optical coherence tomography of a 24-year-old male patient were documented. Results: The patient, with a preoperative best-corrected visual acuity (BCVA) of 1.0, developed endophthalmitis following 27-gauge pars plana vitrectomy for symptomatic vitreous floaters. After a series of treatments, including emergent vitreous tap and silicone oil injection, antibiotic treatment, and silicone oil removal, the patient regained a BCVA of 0.6. Conclusion: Although rare, the potential risk of endophthalmitis should be explicitly discussed with patients considering surgical intervention for vitreous floaters.

Abstract Background Anaplasma spp. are tick-transmitted bacteria that infect a wide variety of wild and domestic animals. These pathogens exhibit a high degree of biological diversity, broad geographical distribution, and represent a serious threat to veterinary and public health worldwide. Results A novel Anaplasma species was identified in Haemaphysalis qinghaiensis (Ixodidae) in northwestern China and was molecularly characterized by comparison of 16S rRNA, gltA, and groEL gene sequences. Of the 414 samples tested, 24 (5.8%) were positive for this Anaplasma species. On the basis of the 16S rRNA gene, this organism has been found to be closely related to and exhibit the highest sequence similarity with A. capra (99.8–99.9%) that was identified in goats and humans in northern China, but was distinct from other known Anaplasma species. Sequence analysis of the gltA and groEL genes revealed that this Anaplasma species was distinct from A. capra considering the lower sequence identity (88.6–88.7% for gltA and 90.6–91.0% for groEL) and a divergent phylogenetic position. Therefore, we described this Anaplasma species as A. capra-like bacteria. Conclusions The present study reports a potential novel Anaplasma species closely related to A. capra in H. qinghaiensis in northwestern China. The zoonotic potential of A. capra-like bacteria needs to be further determined.