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The Dandy–Walker malformation (DWM) is characterized by neuron dysregulation in embryonic development; however, the regulatory mechanisms associated with it are unclear. This study aimed to investigate the role of NADH dehydrogenase 1 alpha subcomplex 4 (NDUFA4) in regulating downstream signaling cascades and neuronal proliferation and apoptosis. Ndufa4 overexpression promoted the proliferation of neurons and inhibited their apoptosis in vitro, which underwent reverse regulation by the Ndufa4 short hairpin RNAs. Ndufa4-knockout (KO) mice showed abnormal histological alterations in the brain tissue, in addition to impaired spatial learning capacity and exploratory activity. Ndufa4 depletion altered the microRNA expressional profiles of the cerebellum: Ndufa4 inhibited miR-145a-5p expression both in the cerebellum and neurons. miR-145a-5p inhibited the proliferation of neurons and promoted their apoptosis. Ndufa4 promoted and miR-145a-5p inhibited the expression of human homer protein homolog 1 and cyclin D2 in neurons. Thus, Ndufa4 promotes the proliferation of neurons and inhibits their apoptosis by inhibiting miR-145a-5p, which directly targets and inhibits the untranslated regions of Homer1 and Ccnd2 expression.

Background This study aimed to examine the roles of anatomical variation in localized and diffuse chronic rhinosinusitis [LCRS and DCRS]) . Methods A database was analyzed retrospectively on patients hospitalized in the Department of Otorhinolaryngology of our university hospital from 2017 to 2020. A total of 281 patients were included and divided into three categories: patients with LCRS, patients with DCRS, and a normal control group. The frequency of anatomical variation, the demographic information, disease type (with or without polyps), symptom visual analogue scale (VAS) scores and Lund-Mackay (L-M) scores were calculated and compared. Results Anatomical variants were observed more frequently in LCRS than DCRS (P Conclusion Anatomical variants were common in CRS, and possibly correlated with LCRS but not with DCRS. The frequency of anatomical variation is not associated with the occurrence of polyps. CT could reflect the severity of disease symptoms to some extent.

The possible mechanism of Acid Scarlet GR degradation by palygorskite/MnO2/Fe3O4 (PMM) activated peroxymonosulfate (PMS) is investigated.

Li–O2 batteries are considered promising electrochemical energy storage devices due to their high specific capacity and low cost.

Organic molecules having emission in the NIR(II) region are emergent and receiving enormous attention. Unfortunately, attaining accountable organic emission intensity around the NIR(II) region is hampered by the dominant internal conversion operated by the energy gap law, where the emission energy gap and the associated internal reorganization energy λ

Lymph node (LN) metastasis affects both the management and prognosis of head and neck squamous cell carcinoma (HNSCC). Here, we explored the relationship between lymphatic metastasis and CEA family member 5 (CEACAM5), including its possible regulatory role in HNSCC. The levels of CEACAM5 in tissues from patients with HNSCC, with and without LN metastases, were assessed by transcriptome sequencing. The associations between CEACAM5 and the N stage of LN metastasis in HNSCC were predicted through The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and a pan-cancer analysis of CEACAM5 expression in 33 common human tumors was conducted. CEACAM5 levels were analyzed in tumor and normal tissue specimens from HNSCC patients and the correlation between CEACAM5 levels and prognosis was evaluated. The influence of CEACAM5 on cell proliferation, invasion, migration, and apoptosis was investigated in HNSCC cell lines, as were the downstream regulatory mechanisms. A mouse model of LN metastasis was constructed. CEACAM5 levels were significantly higher in HNSCC tissue without LN metastasis than in that with LN metastasis. Similar findings were obtained for the clinical specimens. CEACAM5 levels were associated with better clinical prognosis. CEACAM5 was found to inhibit the proliferation and migration and promote the apoptosis of HNSCC cells. A mouse xenograft model showed that CEACAM5 inhibited LN metastasis. In conclusions, CEACAM5 inhibited epithelial–mesenchymal transition (EMT) in HNSCC by reducing murine double minute 2 (MDM2) expression and thereby suppressing LN metastasis. CEACAM5 has potential as both a prognostic marker and a therapeutic target in HNSCC.

Focused ultrasound (FUS)-induced blood-brain barrier (BBB) opening is crucial for enhancing glioblastoma (GBM) therapies. However, an in vivo imaging approach with a high spatial-temporal resolution to monitor the BBB opening process in situ and synchronously is still lacking. Herein, we report the use of indocyanine green (ICG)-dopped microbubbles (MBs-ICG) for visualizing the FUS-induced BBB opening and enhancing the photothermal therapy (PTT) against GBM. The MBs-ICG show bright fluorescence in the second near-infrared window (NIR-II), ultrasound contrast, and ultrasound-induced size transformation properties. By virtue of complementary contrast properties, MBs-ICG can be successfully applied for cerebral vascular imaging with NIR-II fluorescence resolution of ∼168.9 μm and ultrasound penetration depth of ∼7 mm. We further demonstrate that MBs-ICG can be combined with FUS for in situ and synchronous visualization of the BBB opening with a NIR-II fluorescence signal-to-background ratio of 6.2 ± 1.2. Finally, our data show that the MBs-ICG transform into lipid-ICG nanoparticles under FUS irradiation, which then rapidly penetrate the tumor tissues within 10 min and enhance PTT in orthotopic GBM-bearing mice. The multifunctional MBs-ICG approach provides a novel paradigm for monitoring BBB opening and enhancing GBM therapy.

A global survey indicates that genetic syndromes affect approximately 8% of the population, but most genetic diagnoses can only be performed after babies are born. Abnormal facial characteristics have been identified in various genetic diseases; however, current facial identification technologies cannot be applied to prenatal diagnosis. We developed Pgds-ResNet, a fully automated prenatal screening algorithm based on deep neural networks, to detect high-risk fetuses affected by a variety of genetic diseases. In screening for Trisomy 21, Trisomy 18, Trisomy 13, and rare genetic diseases, Pgds-ResNet achieved sensitivities of 0.83, 0.92, 0.75, and 0.96, and specificities of 0.94, 0.93, 0.95, and 0.92, respectively. As shown in heatmaps, the abnormalities detected by Pgds-ResNet are consistent with clinical reports. In a comparative experiment, the performance of Pgds-ResNet is comparable to that of experienced sonographers. This fetal genetic screening technology offers an opportunity for early risk assessment and presents a non-invasive, affordable, and complementary method to identify high-risk fetuses affected by genetic diseases. Additionally, it has the capability to screen for certain rare genetic conditions, thereby enhancing the clinic’s detection rate.

In Escherichia coli, transcription-translation coupling is mediated by NusG. Although chloroplasts are descendants of endosymbiotic prokaryotes, the mechanism underlying this coupling in chloroplasts remains unclear. Here, we report transcription-translation coupling through AtNusG in chloroplasts. AtNusG is localized in chloroplast nucleoids and is closely associated with the chloroplast PEP complex by interacting with its essential component PAP9. It also comigrates with chloroplast ribosomes and interacts with their two components PRPS5 (uS5c) and PRPS10 (uS10c). These data suggest that the transcription and translation machineries are coupled in chloroplasts. In the atnusg mutant, the accumulation of chloroplast-encoded photosynthetic gene transcripts, such as psbA, psbB, psbC and psbD, was not obviously changed, but that of their proteins was clearly decreased. Chloroplast polysomic analysis indicated that the decrease in these proteins was due to the reduced efficiency of their translation in this mutant, leading to reduced photosynthetic efficiency and enhanced sensitivity to cold stress. These data indicate that AtNusG-mediated coupling between transcription and translation in chloroplasts ensures the rapid establishment of photosynthetic capacity for plant growth and the response to environmental changes. Therefore, our study reveals a conserved mechanism of transcription-translation coupling between chloroplasts and E. coli, which perhaps represents a regulatory mechanism of chloroplast gene expression. This study provides insights into the underlying mechanisms of chloroplast gene expression in higher plants.

Sewage sludge (SL), Chinese medicinal herbal residues (CMHRs) and the raw materials of biochar (BC) are normally treated as wastes. However, SL, CMHRs and BC are potential candidates for soil amendments. The performances of soils amended with three different proportions (5%, 10% and 20% on a dry-weight basis) of SL-BC and SL-CMHR-BC in terms of ameliorating soil properties and attenuating antibiotics in soil–plant systems were investigated with two common crop species: carrot and lettuce. The amended soils in general showed higher nutrient levels than the control soils, and particularly for the 20% SL-CMHR-BC. The soils with 10% or 20% SL-BC or SL-CMHR-BC apparently retarded the germination performances of the two crop species, but the negative effects were not noticeable after a growing period. Six target antibiotics, amoxicillin (AMX), tetracycline (TC), sulfamethazine (SMX), norfloxacin (NOR), erythromycin (ERY) and chloramphenicol (CAP), were applied for growing the crops by using irrigation water with 3 μg L−1 (IW3) and 30 μg L−1 (IW30) of each antibiotic. The amended soils led to lower levels of antibiotics in the soils and crop tissues as compared with the control, with the 20% SL-CMHR-BC soils showing the most pronounced effect. The effects of the soil amendments on the bioconcentration factor (BCF) varied, but generally with lower values in the amended soils. Both SL-BC and SL-CMHR-BC were proven in the study as potential soil amendments for alleviating the environmental dispersal and human exposure risks of different antibiotics, and specifically 20% SL-CMHR-BC.

The spatial distribution of rockhead profile has a significant impact on the design and construction of geotechnical engineering structures. Limited by the economic and technical conditions, the borehole data of specific sites are often sparse, which brings great challenges to the accurate prediction of rockhead profile. In this study, a Gaussian process regression (GPR) method is used to predict the rockhead profile. Borehole data from a construction site in Hong Kong are used to evaluate the ability of the GPR method to predict rockhead profile. Besides, the influences of the amount of borehole data on the accuracy of the GPR model and the spatial prediction results of rockhead are investigated. The results indicate that the GPR model based on the square exponential and the Matérn covariance function can obtain more accurate prediction results, and the GPR model with limited borehole data can provide a reasonable prediction interval for rockhead depth. With the increase of borehole data, the generalization ability and prediction accuracy of the GPR model gradually improves. In engineering practice, the prediction accuracy and uncertainty degree of the GPR model can be used to judge whether it is necessary to continue to increase borehole data.

Neuroblastoma is a common pediatric cancer, where preclinical studies have suggested chemotherapy resistance is driven by a mesenchymal-like gene expression program. However, the poor clinical outcomes imply we need a better understanding of the relationship between patient tumors and preclinical models. Here, we generated single-cell RNA-seq maps of neuroblastoma cell lines, patient-derived xenograft models (PDX), and a genetically engineered mouse model (GEMM). We developed an unsupervised machine learning approach to compare the gene expression programs found in preclinical models to a large cohort of human neuroblastoma tumors. The dominant adrenergic programs were well preserved in preclinical models, but contrary to previous reports do not unambiguously map to an obvious cell of origin. The mesenchymal-like program was less clearly preserved, and primarily restricted to cancer-associated fibroblasts and Schwann-like cellsin vivo. Surprisingly however, we identified a subtle, weakly expressed, mesenchymal-like program in otherwise adrenergic cancer cells in some high-risk tumors. This program appears distinct from mesenchymal cell lines but was maintained in PDX and a similar program could be chemotherapy-induced in our GEMM after only 24 hours, suggesting an uncharacterized therapy-escape mechanism. Collectively, our findings advance the understanding of neuroblastoma heterogeneity and can inform the development of new treatments.

Combination chemotherapy is crucial for achieving durable cancer cures, however, developing safe and effective drug combinations has been a significant challenge. To improve this process, we conducted large-scale targeted CRISPR knockout screens in drug-treated cells, creating a genetic map of druggable genes that sensitize cells to commonly used chemotherapeutics. We prioritized neuroblastoma, the most common pediatric solid tumor, where 50% of high-risk patients do not survive. Our screen examined all druggable gene knockouts in 18 cell lines (10 neuroblastoma, 8 others) treated with 8 widely used drugs, resulting in 94,320 unique combination-cell line perturbations, which is comparable to the largest drug combination screens ever reported. Remarkably, using dense drug-drug rescreening, we found that the top CRISPR-nominated drug combinations were far more synergistic than standard-of-care combinations, suggesting existing combinations could be improved. As proof of principle, we discovered that inhibition of PRKDC, a component of the non-homologous end-joining pathway, sensitizes high-risk neuroblastoma cells to the standard-of-care drug doxorubicinin vitroandin vivousing PDX models. Our findings provide a valuable resource for the development of improved chemotherapeutic strategies and demonstrate the feasibility of using targeted CRISPR knockout to discover new combinations with common chemotherapeutics, a methodology with application across all cancers.

In recent years, the emergence and development of single-cell sequencing technologies have provided unprecedented opportunities to analyze deoxyribonucleic acid, ribonucleic acid and proteins at single-cell resolution. The advancements and reduced costs of high-throughput technologies allow for parallel sequencing of multiple molecular layers from a single cell, providing a comprehensive insight into the biological state and behavioral mechanisms of cells through the integration of genomics, transcriptomics, epigenomics and proteomics information. Researchers are actively working to further improve the cost-effectiveness, stability and high-throughput capabilities of single-cell multi-omics sequencing technologies and exploring their potential in precision medicine through clinical diagnostics. This review aims to survey the cutting-edge advancements in single-cell multi-omics sequencing, summarizing the representative technologies and their applications in profiling complex diseases, with a particular focus on tumors.

Background: Psoriasis is a common chronic inflammatory dermatosis characterized by scaly erythema and plaques. This study explored the specific mechanism of LncRNA MALAT1 in the occurrence and development of psoriasis. Methods: We collected serum from psoriasis patients and healthy subjects and measured the expression of IL-17 in serum by ELISA. HaCaT cells were stimulated with 80 ng/mL IL-17 and simultaneously transfected with shMALAT1 or were treated with Secukinumab (anti-IL-17A). The CCK-8 and EdU experiments were used to detect cell viability and proliferation, flow cytometry showed the level of cell cyle, and corresponding cyclins were measured by WB and RT-QPCR, and changes in a series of LncRNAs were detected. A luciferase activity analysis and ChIP assay verified the targeting relationship between MALAT1 and p65. Results: IL-17 treatment of HaCaT cells promoted cell proliferation and increased MALAT1 expression. The binding of p65 to the promoter of MALAT1 promoted keratinocyte proliferation. The proliferation of HaCaT cells induced by IL-17 was repressed by Secukinumab. The expression of miR-125b was notably reduced in cells treated with IL-17, whereas Secukinumab rescued the expression of miR-125b. IL-17 treatment resulted in elevated BRD4 expression, which was attenuated by Secukinumab. Conclusions: IL-17 stimulates HaCaT cell proliferation by inducing high expression of MALAT1, and p65 binds to the promoter of MALAT1 to promote its expression, which may provide a novel direction for the treatment of psoriasis.

Being one of the core techniques of magnetic surgery, magnetic compression technique (MCT) has been used for digestive tract anastomosis reconstruction in experimental studies. This study verified the feasibility of gastroenteric anastomosis through natural orifice using MCT in rats.The parent and daughter magnets were designed and manufactured for oral and anal insertion in 20 Sprague-Dawley rats. After anesthesia, the parent magnet was inserted into the colon spleen area through the anus, and the daughter magnet was inserted into the stomach through the mouth. Then the two magnets were positioned to attract each other and bind together. The position of the two magnets was monitored using X-ray. The time required for the formation of the anastomosis and expulsion of the magnets were recorded. 2 weeks later, the animal was sacrificed and the anastomotic specimen was obtained which was observed under naked eye and microscope.The gastroenteric anastomosis was successfully performed via natural orifices in 18 out of 20 rats. The mean time to construct the anastomosis was 3.78 ± 0.88 min. X-ray examination showed that the magnets were in the appropriate position in 17 rats. The magnets were excreted in 9.47 ± 1.62 days after surgery. The gross and microscopic examination of the specimen showed that the anastomoses were patent and the mucosa at the anastomotic was smooth. The mean bursting pressure of the anastomosis was 136.94 ± 6.79 mmHg.It is feasible to perform gastroenteric anastomosis through natural orifices by MCT.

Transcriptome sequencing has emerged as an important research tool for exploring the mysteries of life at the single-cell level. However, its wide application is limited by the bias associated with the amplification reactions which is essential for library building of trace RNA. In this study, low-melting-point agarose was added to the amplification reactions to take advantage of its molecular crowding effect and polymer cross-linked structure to improve the sensitivity of the reactions and reduce bias. To further evaluate the performance of the method, it was applied to transcriptome sequencing of microregion samples from brain tissue sections of mice with Parkinson's disease at the single cell level. The results showed that agarose PCR had better performance than in-tube PCR. Further application of agarose PCR to transcriptome library sequencing could obtain data closer to that of unamplified. With the addition of low melting point agarose, the sensitivity of the amplification reaction was significantly increased, while homogeneity was increased by approximately 2-fold. Not only that, but this work also provides 11% sensitivity improvement for spatial transcriptomic study on Parkinson's disease-associated gene detection. The agarose PCR provides a new tool for efficient and homogeneous amplification of trace samples and can be widely used for spatial transcriptome library sequencing and studies.

Thioredoxin-interacting protein (TXNIP) was originally named vitamin D3 upregulated protein-1 (VDUP1) because of its ability to bind to thioredoxin (TRX) and inhibit TRX function and expression. TXNIP is an alpha-arrestin protein that is essential for redox homeostasis in the human body. TXNIP may act as a double-edged sword in the cell. The balance of TXNIP is crucial. A study has shown that TXNIP can travel between diverse intracellular locations and bind to different proteins to play different roles under oxidative stress. The primary function of TXNIP is to induce apoptosis or pyroptosis under oxidative stress. TXNIP also inhibits proliferation and migration in cancer cells, although TXNIP levels decrease, and function diminishes in various cancers. In this review, we summarized the main structure, binding proteins, pathways, and the role of TXNIP in diseases, aiming to explore the double-edged sword role of TXNIP, and expect it to be helpful for future treatment using TXNIP as a therapeutic target.

The switched inertance hydraulic converter is a sub-domain of digital hydraulics which relies on digital switching to adjust pressure or flow instead of the dissipation of power by throttling, providing an energy-efficient alternative to conventional proportional or servo valve-controlled systems. The high-speed switching valve is a key component to realise the digital switching and its switching characteristics has significant effects on the performance of switched inertance hydraulic converters. In this article, the switching characteristics of a high-speed rotary valve are investigated. The switching orifice area of the valve is calculated based on the movement of the valve components with a consideration of the design of the valve body and leakage. This is validated using the computational fluid dynamics model and in experiments. The valve is theoretically modelled considering the switching orifice, leakage, transition throttling and compressibility effect, and the results are validated by computational fluid dynamics and experimental tests. The valve is able to deliver a flow rate of 40 L/min at a pressure drop of 10 bar and switch at the maximum frequency of 317 Hz, with a switching transition time of about 1 ms, which shows promising performance for the use in digital hydraulics. The theoretical and computational fluid dynamics models can assist the design and optimisation of digital high-speed rotary valves, which can be very useful for understanding, analysing and optimising the characteristics and performance of switched inertance hydraulic converters in digital hydraulics.

The aim of this prospective study is to evaluate the performance of the intermediate 16-week ultrasound in fetuses with increased nuchal translucency (NT) and a normal chromosomal microarray analysis (CMA).During a one-year period, a detailed ultrasound was performed at 16 week' gestation for patients with an increased NT (≥3.5 mm) and normal CMA. Pregnancy work-up included a traditional 22-week ultrasound scan, an echocardiography, and the option of a 10-gene Rasopathy panel after a normal 16-week scan. Abnormal findings and pregnancy outcomes were collected and analyzed.In 52 fetuses with an isolated increased NT and normal CMA, 14 (26.5%) were noted to have structural defects on the 16-week ultrasound. Intrauterine fetal death occurred in one (1.9%) case identified by the 16-week scan. Of the remaining 37 cases, six opted for a RASopathy panel. In this group, one case of Noonan syndrome was detected. One case of unilateral duplex kidney had not been found until the 22-week scan. One case of fetal growth restriction was identified in the third trimester. The remaining 34 cases proceeded with normal ultrasound to term.The 16-week ultrasound scan performed on fetuses with increased NT and normal CMA could detect the majority of structural abnormalities that are expected to be identified traditionally at 20-24 weeks.

We aimed to investigate the value of exome sequencing (ES) in fetuses with callosal anomalies (CA) with or without other structural anomalies, but with normal findings by karyotyping and chromosome microarray analysis (CMA).Cases with CA with or without other structural anomalies were screened for eligibility. Fetuses with abnormal karyotyping or CMA results were excluded. We performed ES on DNA samples from eligible fetus-parental trios and identified diagnostic genetic variants based on the ultrasonographic features.A total of 50 eligible fetus-parental trios were successfully analyzed by ES. We found 17 likely pathogenic or pathogenic variants in 14 genes from 17 fetuses, with a total proportion of diagnostic genetic variants equal to 34.0% (17/50). Of the 17 cases with a diagnosis, 10 (29.4%, 10/35) were isolated and 7 (43.8%, 7/15) were non-isolated. Pregnancy outcome data showed that 70.0% (7/10) of the surviving isolated CA fetuses with negative ES results had a good prognosis in early childhood.Our study used ES prenatally for CA and showed that ES can be used diagnostically to define the molecular defects that underlie unexplained CA. Most subjects with isolated CA with negative results for genetic causes will have a favorable prognosis in early childhood.

The application of an exogenous polymer matrix to construct aggregation-induced emission (AIE) nanoprobes promotes the utility of AIE luminogens (AIEgens) in diagnosing brain diseases. However, the limited fluorescence (FL) and low active-targeting abilities of AIE-based nanoprobes impede their imaging application. Here, we employed endogenous albumin as an effective matrix to encapsulate AIEgens to enhance FL quantum yield (QY) and active-targeting ability. The albumin-consolidated strategy effectively inhibited the intramolecular vibration of AIEgens and enhanced endocytosis mediated by the gp60 receptor. The QYs of three kinds of albumin-based AIE nanoprobes with FL emissions ranging from the visible (400-650 nm) to the second near-infrared (NIR-II, 1000-1700 nm) region was at least 10% higher, and the tumor-targeting efficiency was ∼25% higher, compared with those of nanoprobes constructed by the exogenous polymer. Albumin-based AIE nanoprobes have achieved active-targeting NIR-II imaging of brain tumors and cerebrovascular imaging with a high signal-to-background ratio (SBR, ∼90) and high resolution (∼70 μm) in mouse models. Therefore, the albumin-based AIE nanoprobes will enable FL imaging-guided surgery of brain tumors and cerebral ischemia, which will improve surgical efficacy to prevent recurrence and side effects.

An on-site activated aptasensing platform is constructed for highly reliable ATP monitoring in cancer cells both in vitro and in vivo by combining tumor-specific activatable MnO2 with the stimuli-responsive cascade DNA amplifier.

In this work, based on first-principles calculations, we theoretically predict two kinds of two-dimensional tetragonal Si–Se compounds, Si2Se2 and SiSe2, as the anode materials for alkali metal-ion batteries.

Motivation: Magnetic–inertial measurement units (MIMUs) and flexible sensors are widely used in the wearable measurement system for human motion monitoring, clinical gait detection, and robotics motion control. However, MIMUs demonstrate measurement error due to magnetic disturbance in the indoor environment, and flexible sensors usually have low performance on linearity and accuracy. Objective: This article is intended to eliminate the low-accuracy problem caused by magnetic disturbances and improve the measurement accuracy of MIMU–flexible-sensor-based wearable systems. Approach: 1) a three-stage real-time adaptive anti-disturbance data fusion (RT-ADF) algorithm is proposed, which contains an anti-disturbance filter based on a double Mahony filter along with a state observer, a signal holder for sensors’ data transmit synchronously, and a data fusion based on an adaptive Kalman filter; 2) the proposed algorithm is used and validated its performance on a designed MIMU–flexible sensor wearable system; and 3) ten groups of knee motions (flexion/extension), ten groups of hip motions (adduction/abduction), and ten groups of elbow motions (flexion/extension) have been done by seven subjects in the experiments. Main Results: The designed multisensor wearable system based on the presented data fusion algorithm demonstrates a high-accuracy performance under the magnetic disturbance environment, and the maximum root mean square error (RMSE) of the measured continuous 3-D motion angle of the knee, hip, and elbow cross all the experiments was 1.23°, 1.15°, and 3.67° for each axis.

The MMPs are endogenous proteolytic enzymes that require zinc and calcium as cofactors. MMP9 is one of the most complex matrix metalloproteinases in the gelatinase family and has many biological functions. In mammals, mmp9 is thought to be closely associated with cancer. However, studies in fish have rarely been reported. In this study, to understand the expression pattern of the ToMMP9 gene and its association with the resistance of Trachinotus ovatus to Cryptocaryon irritans, the sequence of the MMP9 gene was obtained from the genome database. The expression profiles were measured by qRT–PCR, the SNPs were screened by direct sequencing, and genotyping was performed. The ToMMP9 gene contained a 2058 bp ORF encoding a putative amino acid sequence of 685 residues. The homology of the ToMMP9 in teleosts was more than 85%, and the genome structure of ToMMP9 was conserved in chordates. The ToMMP9 gene was expressed in different tissues of healthy individuals and was highly expressed in the fin, the gill, the liver and the skin tissues. The ToMMP9 expression in the skin of the infected site and its adjacent sites increased significantly after C. irritans infection. Two SNPs were identified in the ToMMP9 gene, and the SNP (+400A/G) located in the first intron was found to be significantly associated with the susceptibility/resistance to C. irritans. These findings suggest that ToMMP9 may play an important role in the immune response of T. ovatus against C. irritans.

Objective: To assess the clinical performance of the human papillomavirus (HPV) 16 18/45 genotype assay (AHPV-GT) combined with age stratification in triaging women with histologic low-grade squamous intraepithelial lesion/cervical intraepithelial neoplasia grade 1 (LSIL [CIN1]) preceded by HPV E6/E7 mRNA assay (Aptima HPV, AHPV) positive/normal or mildly abnormal cytology. Design: Longitudinal study. Setting: Gynaecological clinic in Huzhou Maternity & Child Health Care Hospital, China. Population: Women aged ≥21 years with histologic LSIL (CIN1) preceded by AHPV-positive/normal or mildly abnormal cytology. Methods: Women underwent AHPV-GT testing at baseline and were followed at 6-month intervals for up to 2 years. At each follow-up, women with abnormal cytology or AHPV positivity were referred for colposcopy and then biopsy if indicated. Main outcome measures: The 2-year cumulative incidence rates (CIRs) of CIN3+ stratified by baseline AHPV-GT genotyping. Results: Of 349 eligible women, 25 women (7.2%) progressed, 301 (86.2%) regressed, and 23 (6.6%) persisted during the follow-up. The 2-year CIRs of CIN3+ in AHPV-GT-positive women were both significantly higher than those in AHPV-GT-negative women overall (8.6% vs. 1.7%, P = 0.014) and in the ≥25-year-old group (10.9% vs. 1.5%, P = 0.002) but slightly higher in the 21–24-year-old group ( P > 0.05). Conclusions: AHPV-GT testing with age stratification is effective for triaging women with histologic LSIL (CIN1) preceded by AHPV-positive/normal or mildly abnormal cytology. Immediate treatment is a rational recommendation for women ≥ 25 years old with histologic LSIL (CIN1) preceded by AHPV-GT positivity when good surveillance is not assured.

Background Gastric cancer (GC) has high morbidity and mortality. Moreover, because GC has no typical symptoms in the early stages, most cases are already in the advanced stages by the time the symptoms appear, thus resulting in poor prognosis and a low survival rate. Endoscopic submucosal dissection (ESD) can realize the early detection and diagnosis of GC and become the main surgical method for early GC. However, ESD has a steep learning curve and high technical skill requirements for endoscopists, which is not conducive to its widespread implementation and advancement. This study aimed to evaluate the safety and efficacy of magnetic anchor technique (MAT)-assisted ESD in early GC. Method This was an ex vivo animal experiment. The experimental model was the isolated stomachs of pigs. The magnetic anchor device for auxiliary ESD comprised three parts, an anchor magnet (AM), a target magnet (TM), and a soft tissue clip. Under gastroscopic guidance, the soft tissue clip and the TM were delivered to the pre-marked mucosal lesion through the gastroscopic operating hole. The soft tissue clip and the TM were connected by a thin wire through the TM tail structure. The soft tissue clip was released by manipulating the operating handle of the soft tissue clip in a way that the soft tissue clip and the TM were fixed to the lesion mucosa. In vitro, ESD is aided by maneuvering the AM such that the mucosal dissection surface is exposed. Result During the operation, there was no detachment of the soft tissue clip and TM and no mucosal tearing. The magnetic force between the AM and TM provided good mucosal exposure and sufficient tissue tension for ESD. The mucosal lesion was completely peeled off, and the operation was successful. Conclusion MAT-ESD is safe and effective for early gastric cancer. It provides a preliminary basis for subsequent internal animal experiments and clinical research.

Objective Patients with hypopharyngeal carcinoma (HPC) have a poor prognosis mainly because of lymphatic metastasis (LM). This research aimed to determine the PKM2 role in LM in HPC and the underlying molecular mechanism contributing to this phenomenon. Methods PKM2 in HPC was studied for its expression and its likelihood of overall survival using TCGA dataset. Kaplan-Meier and COX's regression analysis were employed to determine PKM2's prognostic value, while western blotting, qRT-PCR, and IHC were employed to confirm PKM2 expression. Methods including gain- and loss-of-function were used to examine the PKM2 role in HPC metastasis in vitro and in vivo. After that, Transwell assay, Wound Healing assay, Flow cytometry, EdU, and an in vivo Popliteal lymphatic metastasis mice model were employed to show the role of PKM2 in FaDu cell lines. In vitro and in vivo studies also confirmed lymphatic metastasis's mechanism. Results Prominent PKM2 overexpression was seen in patients with LM of HPC, and there was an inherent relationship between a high PKM2 level and poor prognosis. In vitro research showed that knocking down PKM2 decreased tumor cell invasion, migration, and proliferation while promoting apoptosis and inhibiting epithelial-mesenchymal transition (EMT), but overexpressing PKM2 had the reverse effect. Animal studies suggested that PKM2 may facilitate tumor development and LM. Conclusions Our findings suggest that PKM2 may be a tumor's promoter gene of LM, which may promote LM of HPC by regulating EMT. PKM2 may be a biomarker of metastatic potential, ultimately providing a basis for exploring new therapeutic targets.

Agricultural practices such as wastewater irrigation and manure application may contaminate soils with antibiotics and, consequently, lead to human health risk. The co-application of three waste-derived materials, sewage sludge (SL), Chinese medicinal herbal residues (CMHR) and biochar (BC), as a soil amendment was proposed recently for minimizing the antibiotic amount in crop tissues. The fate of six antibiotics—amoxicillin, tetracycline, sulfamethazine, norfloxacin, erythromycin and chloramphenicol—were investigated in a greenhouse soil-plant system with a fruit crop species: tomato. The pots were mixed with 5%, 10% or 20% SL-BC and SL-CMHR-BC and irrigated with wastewater with 3 μg/L or 30 μg/L antibiotics. The pot containing 20% SL-CMHR-BC captured the lowest antibiotic concentration in soils and tomato tissues. Norfloxacin was the most abundant antibiotic in the fruits, followed by tetracycline. The pot containing 20% SL-CMHR-BC significantly lowered the bioconcentration factor of the fruit, while its effects on the translocation factor were more varied. Current and some previous data were used to assess the human health risk of consuming carrot, lettuce and tomato. The estimated daily intake suggested a negligible risk to human health in general compared with the acceptable daily intake, except for CAP. A concentration of 20% SL-CMHR-BC helps minimize the human exposure risk to antibiotics contamination in edible crops.

Background Small bowel capsule endoscopy (SBCE) is recommended as the first choice of small bowel evaluation for suspected small bowel bleeding (SBB). However, there is no consensus on the cleansing criteria prior to SBCE. Aim We aimed to assess the effectiveness of the purgative regimen and the overnight fasting only method before undergoing SBCE. Methods This was a retrospective study of 102 patients who underwent SBCE to detect the source of active or sub-acute overt suspected SBB. 63 Patients in Group A consumed 2 L of PEG (Polyethylene glycol) before SBCE after an overnight fast; whereas 39 patients in Group B performed 12 hours overnight fast before the procedure. The primary endpoint was lesion findings and diagnostic yield, and the secondary endpoints were clinical outcomes, capsule endoscopy completion rate (CECR), transit time and the small bowel visualization quality (VQ). RESULTS The positive finding was ascertained in 38 patients in Group A (60.3%), and 18 in Group B (46.2%; P = 0.162). There was no significant difference in diagnosis yield in 2 groups (47.6% vs. 51.3%; P = 0.719), the same as the sensitivity (53.6% vs. 58.8%; P = 0.627) and specificity (71.4% vs. 100%; P = 0.470). The percentage of excellent or good small bowel VQ in Group A was significantly more than in Group B (57.2% vs. 38.5%, P = 0.0012). The median small-bowel transit time for Group A was statistically significant shorter than Group B (400 min vs. 519 min; P = 0.01). No evidence of differences was detected between the two groups in further treatment methods and prognosis(P = 0.209). CONCLUSION 2L PEG-based bowel preparation before SBCE does not result in improvement of diagnostic yield or clinical outcomes, although the small bowel visualization quality is enhanced.

PurposeAccurate and timely cost prediction is critical to the success of construction projects which is still facing challenges especially at the early stage. In the context of rapid development of machine learning technology and the massive cost data from historical projects, this paper aims to propose a novel cost prediction model based on historical data with improved performance when only limited information about the new project is available.Design/methodology/approachThe proposed approach combines regression analysis (RA) and artificial neural network (ANN) to build a novel hybrid cost prediction model with the former as front-end prediction and the latter as back-end correction. Firstly, the main factors influencing the cost of building projects are identified through literature research and subsequently screened by principal component analysis (PCA). Secondly the optimal RA model is determined through multi-model comparison and used for front-end prediction. Finally, ANN is applied to construct the error correction model. The hybrid RA-ANN model was trained and tested with cost data from 128 completed construction projects in China.FindingsThe results show that the hybrid cost prediction model has the advantages of both RA and ANN whose prediction accuracy is higher than that of RA and ANN only with the information such as total floor area, height and number of floors.Originality/value(1) The most critical influencing factors of the buildings’ cost are found out by means of PCA on the historical data. (2) A novel hybrid RA-ANN model is proposed which proved to have the advantages of both RA and ANN with higher accuracy. (3) The comparison among different models has been carried out which is helpful to future model selection.

The incidence of colorectal cancer is high. Early detection, diagnosis and treatment are particularly important. Endoscopic submucosal dissection (ESD) is used to treat early-stage cancer, and the ESD-assisted magnetic anchor technique (MAT) has greatly changed the operating experience of endoscopists. The present study aimed to determine the feasibility of MAT-assisted ESD for the treatment of early-stage colorectal cancer. We designed and manufactured a magnetic anchor device consisting of a target magnet (TM), an anchor magnet (AM), and a soft-tissue clip. The TM was fixed on the diseased mucosa by means of the soft-tissue clip, and the AM was located exterior to the colorectal sample. By changing the position of the AM, the TM was pulled to fully expose the mucosal surface and maintain sufficient tissue tension to assist the ESD. MAT-assisted ESD was successfully completed in all 12 isolated colorectal samples. During the operation, there were no instances of TM detachment or mucosal tears. The interaction between the magnets provided sufficient mucosal tissue tension and a clear mucosal dissection surface, which greatly changed the ESD experience. MAT-assisted ESD is a feasible procedure for the treatment of early-stage colorectal cancer and has great potential for clinical application.