Search

Abstract Objective This study aims to explore the appropriate surgical treatment method for acute intestinal obstruction caused by gastrointestinal foreign bodies in children through a comparison of clinical characteristics in patients treated via laparoscopically assisted approach and open surgery. Methods This study retrospectively analyzed 12 children with acute intestinal obstruction caused by gastrointestinal foreign bodies treated at Shanghai Children’s Hospital and Huzhou Maternity and Child Care Hospital from June 2019 to June 2024. Basic information, treatment methods, and prognoses of the patients were collected. General data, operation time, postoperative fasting time, postoperative hospital stay, and intraoperative and postoperative complications were compared between the two groups. Categorical data were compared using Fisher’s exact test. Normally distributed continuous data were expressed as mean ± standard deviation and analyzed using an independent samples t-test; non-normally distributed data were expressed as M (P25, P75) and analyzed using the non-parametric Mann-Whitney U test. Results Six cases underwent laparoscopic transumbilical extended incision, successfully extracting the intestines and removing the foreign bodies without converting to open surgery. Compared to Six cases undergoing traditional open surgery during the same period, the postoperative fasting time and postoperative hospital stay in the laparoscopic group were 4 (5 ± 3.65) days and 5.5 (5 ± 7.5) days, respectively, while in the traditional open surgery group, they were 5 (4.25 ± 6) days and 6 (5 ± 8.6) days, respectively; the differences were statistically significant (P

Abstract Plants are capable of altering root growth direction to curtail exposure to a saline environment (termed halotropism). The root cap that surrounds root tip meristematic stem cells plays crucial roles in perceiving and responding to environmental stimuli. However, how the root cap mediates root halotropism remains undetermined. Here, we identified a root cap-localized NAC transcription factor, SOMBRERO (SMB), that is required for root halotropism. Its effect on root halotropism is attributable to the establishment of asymmetric auxin distribution in the lateral root cap (LRC) rather than to the alteration of cellular sodium equilibrium or amyloplast statoliths. Furthermore, SMB is essential for basal expression of the auxin influx carrier gene AUX1 in LRC and for auxin redistribution in a spatiotemporally-regulated manner, thereby leading to directional bending of roots away from higher salinity. Our findings uncover an SMB-AUX1-auxin module linking the role of the root cap to the activation of root halotropism.

Fluorescence flow cytometry is a powerful instrument to distinguish cells or particles labelled with high-specificity fluorophores. However, traditional flow cytometry is complex, bulky, and inconvenient for users to adjust fluorescence channels. In this paper, we present a modular fluorescence flow cytometry (M-FCM) system in which fluorescence channels can be flexibly arranged. Modules for particle focusing and fluorescence detection were developed. After hydrodynamical focusing, the cells were measured in the detection modules, which were integrated with in situ illumination and fluorescence detection. The signal-to-noise ratio of the detection reached to 33.2 dB. The crosstalk among the fluorescence channels was eliminated. The M-FCM system was applied to evaluate cell viability in drug screening, agreeing well with the commercial cytometry. The modular cytometry presents several outstanding features: flexibility in setting fluorescence channels, cost efficiency, compact construction, ease of operation, and the potential to upgrade for multifunctional measurements. The modular cytometry provides a multifunctional platform for various biophysical measurements, e.g., electrical impedance and refractive-index detection. The proposed work paves an innovative avenue for the multivariate analysis of cellular characteristics.

Pathogenic microorganisms play a crucial role in the global disease burden due to their ability to cause various diseases and spread through multiple transmission routes. Immunity tests identify antigens related to these pathogens, thereby confirming past infections and monitoring the host’s immune response. Traditional pathogen detection methods, including enzyme-linked immunosorbent assays (ELISAs) and chemiluminescent immunoassays (CLIAs), are often labor-intensive, slow, and reliant on sophisticated equipment and skilled personnel, which can be limiting in resource-poor settings. In contrast, the development of microfluidic technologies presents a promising alternative, offering automation, miniaturization, and cost efficiency. These advanced methods are poised to replace traditional assays by streamlining processes and enabling rapid, high-throughput immunity testing for pathogens. This review highlights the latest advancements in microfluidic systems designed for rapid and high-throughput immunity testing, incorporating immunosensors, single molecule arrays (Simoas), a lateral flow assay (LFA), and smartphone integration. It focuses on key pathogenic microorganisms such as SARS-CoV-2, influenza, and the ZIKA virus (ZIKV). Additionally, the review discusses the challenges, commercialization prospects, and future directions to advance microfluidic systems for infectious disease detection.

Abstract Reconfigurable modular microfluidics presents an opportunity for flexibly constructing prototypes of advanced microfluidic systems. Nevertheless, the strategy of directly integrating modules cannot easily fulfill the requirements of common applications, e.g., the incorporation of materials with biochemical compatibility and optical transparency and the execution of small batch production of disposable chips for laboratory trials and initial tests. Here, we propose a manufacturing scheme inspired by the movable type printing technique to realize 3D free-assembly modular microfluidics. Double-layer 3D microfluidic structures can be produced by replicating the assembled molds. A library of modularized molds is presented for flow control, droplet generation and manipulation and cell trapping and coculture. In addition, a variety of modularized attachments, including valves, light sources and microscopic cameras, have been developed with the capability to be mounted onto chips on demand. Microfluidic systems, including those for concentration gradient generation, droplet-based microfluidics, cell trapping and drug screening, are demonstrated. This scheme enables rapid prototyping of microfluidic systems and construction of on-chip research platforms, with the intent of achieving high efficiency of proof-of-concept tests and small batch manufacturing.

Within the fields of infectious disease diagnostics, microfluidic-based integrated technology systems have become a vital technology in enhancing the rapidity, accuracy, and portability of pathogen detection. These systems synergize microfluidic techniques with advanced molecular biology methods, including reverse transcription polymerase chain reaction (RT-PCR), loop-mediated isothermal amplification (LAMP), and clustered regularly interspaced short palindromic repeats (CRISPR), have been successfully used to identify a diverse array of pathogens, including COVID-19, Ebola, Zika, and dengue fever. This review outlines the advances in pathogen detection, attributing them to the integration of microfluidic technology with traditional molecular biology methods and smartphone- and paper-based diagnostic assays. The cutting-edge diagnostic technologies are of critical importance for disease prevention and epidemic surveillance. Looking ahead, research is expected to focus on increasing detection sensitivity, streamlining testing processes, reducing costs, and enhancing the capability for remote data sharing. These improvements aim to achieve broader coverage and quicker response mechanisms, thereby constructing a more robust defense for global public health security.

Direct interference with Kelch-like ECH-associated protein 1 (Keap1)-Nrf2 protein-protein interaction (PPI) has recently been introduced as an attractive approach to control life-threatening diseases like myocarditis. The present study aimed to investigate the potential application in myocarditis of a series of novel non-naphthalene derivatives as potential Keap1-Nrf2 PPI inhibitors. Our results indicated that the optimal compound K22 displayed the highest metabolic stability and showed notable Keap1-Nrf2 PPI inhibitory activities in vitro. K22 effectively triggered Nrf2 activation and increased the protein and mRNA expression of Nrf2-regulated genes in H9c2 cells. Moreover, pre-treatment with K22 was shown to mitigate LPS-induced damage to H9c2 cells, causing a marked decrease in the levels of inflammatory factors as well as reactive oxygen species (ROS). Furthermore, K22 was also shown to be non-mutagenic in the Ames test. Overall, our findings suggest that K22 may be a promising drug lead as a Keap1-Nrf2 PPI inhibitor for myocarditis treatment.

ABSTRACT In China, low levels of accuracy in predicting when pineapple crops will reach maturity can result from environmental variation such as light changes, fruit overlap, and shading. Therefore, this study proposed the use of an improved RetinaNet algorithm (ECA-Retinanet) based on the ECA attention mechanism. The ECA attention mechanism was embedded into the classification subnet of RetinaNet to improve accuracy in detecting different levels of maturity in pineapples. A new pineapple dataset was collected comprising four different growth stages under mild and severe complex scenarios. The experimental results have shown that the mAP (Mean Average Precision) and F1 score (Balanced Score) of the ECA-Retinanet model were 97.69%, 94.75%, 93.2%, and 90% for identification in mild and severe complex scenarios. These values are 0.42%, 2%, 1.78%, and 1.5% higher than the original RetinaNet model which exceeds those of the six existing state-of-the-art detection models. The results have indicated that the proposed algorithm could be used for accurate identification of pineapple fruit and can detect fruit maturity using ground color images in the natural environment. The study findings provide a technical reference for automatic picking robots and early yield estimation.

Background Primary hypertension is one of the most well-known risk factors for cardiovascular disease. Currently, there is still no ideal indicator for left ventricular end-diastolic pressure. Methods 73 hypertension patients and 37 healthy people were enrolled in this study. Each member was examined with conventional echocardiography including multiple indicators such as Peak mitral valve flow velocity (E, A), E/A, left atrial volume index (LAVl), tissue Doppler (PW-TDI) peak velocities during early and late diastolic mitral valve flow (e ‘), E/e ‘, and GLS. We have collected clinical data from all enrolled members. The above cardiac ultrasound indicators were obtained before the antihypertensive treatment, one month and three months after treatment. Results Left ventricular end-diastolic pressure (LVEDP) was positively correlated and negatively correlated with GLS (r = 0.638, P

Liver fibrosis is characterised by the activation of hepatic stellate cells (HSCs) and matrix deposition. Accumulating evidence has revealed that the oncogenic protein tyrosine phosphatase Src homology 2 domain-containing phosphatase 2 (SHP2) acts as a therapeutic target of fibrosis. Although several SHP2 inhibitors have reached early clinical trials, there are currently no FDA-approved drugs that target SHP2. In this study, we aimed to identify novel SHP2 inhibitors from an in-house natural product library to treat liver fibrosis. Out of the screened 800 compounds, a furanogermacrane sesquiterpene, linderalactone (LIN), significantly inhibited SHP2 dephosphorylation activity in vitro. Cross-validated enzymatic assays, bio-layer interferometry (BLI) assays, and site-directed mutagenesis were used to confirm that LIN directly binds to the catalytic PTP domain of SHP2. In vivo administration of LIN significantly ameliorated carbon tetrachloride (CCl4)-induced HSC activation and liver fibrosis by inhibiting the TGFβ/Smad3 pathway. Thus, LIN or its derivatives could be considered potential therapeutic agents against SHP2-related diseases, such as liver fibrosis or NASH.

BackgroundThe relationship between patent foramen ovale (PFO) and unexplained syncope remains to be illustrated. Therefore, this study aimed to explore the outcomes and prognostic factors for syncope recurrence after PFO closure.MethodsPatients with both large right-to-left shunting (RLS) PFO and unexplained syncope who visited the cardiovascular department of Xiangya Hospital Central South University from 1 January 2017 to 31 December 2021 were consecutively enrolled in our study. The recurrence rate of syncope was compared between the non-closure group (n = 20) and the closure group (n = 91).ResultsA total of 111 patients were finally included. After 31.11 ± 14.30 months of follow-up, only 11% of patients in the closure group had recurrent syncope, which was much lower than that of the non-closure group (11.0 vs. 35%, P = 0.018). We further investigated the possible prognostic factors for syncope recurrence in the closure group and found syncope occurring more than five times preoperatively, hypertension, and residual RLS at 12-month follow-up were significantly correlated with a higher number of recurrences.ConclusionsPFO closure reduced the recurrence rate of unexplained syncope. The efficacy of prevention was prognosticated by factors including the presence or absence of syncope induction, the frequency of syncope episodes, and the presence or absence of hypertension. Syncope recurrence was also related to residual shunts post closure.

Insect-like biomimetic compound eyes have many technological applications. Here, the authors present a facile fabrication scheme involving microfluidics assisted 3D printing that permits to completely separate design, optimization and construction of optical and sensor components.

Fine particle (PM2.5, less than 2.5 micrometers in diameter) is regarded as a harmful carcinogen. However, the molecular mechanisms of the carcinogenic effects of ambient fine particles have not been fully elucidated, and therapeutic options to address this major public health challenge are lacking. Here, we present global gene-specific DNA methylation and transcriptomic (RNA-Seq) analyses after HBE cells were exposed to fine particles on a portable, small, and all-in-one organ-level lung-mimicking air-liquid interface exposure (MALIE) microfluidic platform. A series of cancer-related signal transduction pathways were activated. ErbB1, ErbB2, and ErbB3 gene expression altered by fine particle exposure was the result of changes in the cellular DNA methylome. The protein expression of ErbB family was inhibited by drugs and could regulate downstream Grb2/Raf pathway and Akt/MDM2 pathway. All of the above results indicated that ErbB family may be promising drug targets for air pollution-related diseases and that inhibitor drugs can be used as therapeutic options to treat these diseases.

AimTo detect the composition of the gut microbiota in biliary atresia after Kasai surgery.MethodsInfants within six months after the Kasai operation who were diagnosed by cholangiography at Shanghai Children’s Hospital were enrolled in the study. Fecal samples were collected from diapers, placed into sterile tubes in the inpatient department or outpatient department and frozen at −80°C within half an hour. The gut microbiota was detected by 16S rRNA sequences. Then, the patients that were followed up to one year after the Kasai operation who suffered from cholangitis at least one time were grouped into the BAcho group, and the others were grouped into the BAnoncho group.ResultsNine of 18 BA patients were grouped into the BAcho group, and the others were grouped into the BAnoncho group. In the BAcho group, AST, ALT and GGT were significantly increased compared to the BAnoncho group. The number of total OTUs (operational taxonomic units) in feces was more elevated in the BAnoncho group than in the BAcho group. In the BAnoncho group, the Chao index at the OTU level was significantly increased compared to that in the BAcho group (66.37 ± 21.5 vs. 45.64 ± 11.25, p = 0.02

BackgroundBiliary atresia (BA) is a childhood liver disease characterized by fibrous obstruction and obstruction of the extrahepatic biliary system and is one of the most common and serious biliary disorders in infants. Significant inflammation and fibrosis of the liver and biliary tract are the most prominent features, regardless of the initial damage to the BA. Abnormalities in innate or adaptive immunity have been found in human patients and mouse models of BA. We previously reported that children with BA had abnormal lipid metabolism, including free serum carnitine.ObjectiveTo study gene and protein expression levels of the hepatic peroxisome proliferator-activated receptor-α (PPARα) signaling pathway and farnesoid X receptor (FXR) in BA and BA fibrosis, and assess their clinical values.MethodsLow expression of PPARα and NR1H4 (FXR) in BA were validated in the Gene Expression Omnibus database. Functional differences were determined by gene set enrichment analysis based on of PPARα and NR1H4 expression. BA patients from GSE46960 were divided into two clusters by using consensus clustering according to PPARα, NR1H4, and SMAD3 expression levels, and immunoinfiltration analysis was performed. Finally, 58 cases treated in our hospital were used for experimental verification. (IHC: 10 Biliary atresia, 10 choledochal cysts; PCR: 10 Biliary atresia, 14 choledochal cysts; WB: 10 Biliary atresia, 4 choledochal cysts).ResultsBioinformatics analysis showed that the expression of PPARα, CYP7A1 and NR1H4 (FXR) in the biliary atresia group was significantly lower than in the control group. More BA-specific pathways, including TGFβ signaling pathway, P53 signaling pathway, PI3K-AKT-mTOR signaling pathway, etc., are enriched in BA patients with low PPARα and NR1H4 expression. In addition, low NR1H4 expression is abundant in inflammatory responses, IL6/STAT3 signaling pathways, early estrogen responses, IL2 STAT5 signaling pathways, and TGFβ signaling pathways. The TGFβ signaling pathway was significant in both groups. According to the expression of PPARα, NR1H4 and SMAD3, a key node in TGFβ pathway, BA patients were divided into two clusters using consensus clustering. In cluster 2, SMAD3 expression was high, and PPARα and NR1H4 expression were low. In contrast to cluster 1, immune cell infiltration was higher in cluster 2, which was confirmed by immunohistochemistry. The mRNA and protein levels of PPARα and NR1H4 in BA patients were lower than in the control group by immunohistochemistry, Western blot analysis and real-time PCR.ConclusionsThe downregulation of PPARα and NR1H4 (FXR) signaling pathway may be closely related to biliary atresia.

Regulating redox homeostasis in tumor cells and exploiting oxidative stress to damage tumors is an efficacious strategy for cancer therapy. However, the strengths of organic nanomaterials within this strategy are often ignored. In this work, a light-triggered reactive oxygen species (ROS) damaging nanoamplifier (IrP-T) was developed for enhanced photodynamic therapy (PDT). The IrP-T was fabricated with an amphiphilic iridium complex and a MTH1 inhibitor (TH287). Under green light stimulation, IrP-T catalyzed the oxygen in cells to generate ROS for realizing oxidative damage; meanwhile, TH287 increased the accumulation of 8-oxo-dGTP, further strengthening oxidative stress and inducing cell death. IrP-T could maximize the use of a small amount of oxygen, thus further boosting the efficacy of PDT in hypoxic tumors. The construction of nanocapsules provided a valuable therapeutic strategy for oxidative damage and synergizing PDT.

Iron oxide (Fe3O4), a classical magnetic material, has been widely utilized in the field of biological magnetic resonance imaging Graphene oxide (GO) has also been extensively applied as a drug carrier due to its high specific surface area and other properties. Recently, numerous studies have synthesized Fe3O4/GO nanomaterials for biological diagnosis and treatments, including photothermal therapy and magnetic thermal therapy. However, the biosafety of the synthesized Fe3O4/GO nanomaterials still needs to be further identified. Therefore, this research intended to ascertain the cytotoxicity of Fe3O4/GO after treatment with different conditions in HBE cells. The results indicated the time-dependent and concentration-dependent cytotoxicity of Fe3O4/GO. Meanwhile, exposure to Fe3O4/GO nanomaterials increased reactive oxygen species (ROS) levels, calcium ions levels, and oxidative stress in mitochondria produced by these nanomaterials activated Caspase-9 and Caspase-3, ultimately leading to cell apoptosis.

Abstract Although artemisinin combination therapies have succeeded in reducing the global burden of malaria, multidrug resistance of the deadliest malaria parasite, Plasmodium falciparum, is emerging worldwide. Innovative antimalarial drugs that kill all life-cycle stages of malaria parasites are urgently needed. Here, we report the discovery of the compound JX21108 with broad antiplasmodial activity against multiple life-cycle stages of malaria parasites. JX21108 was developed from chemical optimization of quisinostat, a histone deacetylase inhibitor. We identified P. falciparum histone deacetylase 1 (PfHDAC1), an epigenetic regulator essential for parasite growth and invasion, as a molecular target of JX21108. PfHDAC1 knockdown leads to the downregulation of essential parasite genes, which is highly consistent with the transcriptomic changes induced by JX21108 treatment. Collectively, our data support that PfHDAC1 is a potential drug target for overcoming multidrug resistance and that JX21108 treats malaria and blocks parasite transmission simultaneously.

Intense fluid-dynamic interaction at the impeller outlet strongly affects the unsteady flow and pressure stability within the centrifugal pump. In order to have a better understanding of the pressure fluctuation of centrifugal pumps, a numerical calculation is carried out by using the RNG k-epsilon turbulence model under various flow rates. The numerical calculation results are compared with the experimental results in order to verify the reliability of the calculation model. The amplitude and frequency distribution of pressure fluctuation at the impeller outlet is obtained and analyzed in the time and frequency domain. The research results show that the blade passing frequency is the dominant frequency of the pressure fluctuation. And the pressure fluctuation is a periodic fluctuation. As the flow rate decreases, the periodicity of the pressure fluctuation decreases. Besides, the amplitude and intensity of pressure fluctuation are closely related to flow rate and spatial location. At the low flow rate, the amplitude of pressure fluctuation in the time domain and frequency domain is enlarged greatly, especially near the tongue region. The pressure difference distribution on both sides of the blade surface is extremely uneven, and the pressure changes significantly.

Undoubtedly, SARS-CoV-2 has caused an outbreak of pneumonia that evolved into a worldwide pandemic. The confusion of early symptoms of the SARS-CoV-2 infection with other respiratory virus infections made it very difficult to block its spread, leading to the expansion of the outbreak and an unreasonable demand for medical resource allocation. The traditional immunochromatographic test strip (ICTS) can detect one analyte with one sample. Herein, this study presents a novel strategy for the simultaneous rapid detection of FluB/SARS-CoV-2, including quantum dot fluorescent microspheres (QDFM) ICTS and a supporting device. The ICTS could be applied to realize simultaneous detection of FluB and SARS-CoV-2 with one test in a short time. A device supporting FluB/SARS-CoV-2 QDFM ICTS was designed and had the characteristics of being safe, portable, low-cost, relatively stable, and easy to use, ensuring the device could replace the immunofluorescence analyzer in cases where there is no need for quantification. This device does not need to be operated by professional and technical personnel and has commercial application potential.

Background: Hydrogen is protective against intestinal injury in necrotizing enterocolitis (NEC), mainly through to alleviate inflammation response. The M1 macrophages can promote inflammation. We hypothesized that hydrogen would promote the M1 macrophages conversion during the polarization and reduce the inflammatory factors in NEC.Methods: We used M1 and M2 macrophages induced from RAW264.7 cells and bone marrow-derived macrophages, models of NEC and macrophages derived from spleens, abdominal lymph nodes and lamina propria in model mice. Cytokines, CD16/32 and CD206 were measured by quantitative PCR, flow cytometry. Nuclear factor-κB (NF-κB) p65 were determined by western blot. Histology staining were used to assess the severity of NEC.Results: Macrophages were successfully polarized to M1 or M2 by assessing the expression of inflammatory factors. Pro-inflammatory factors and CD16/32 in M1 macrophages were decreased, and the expression of CD16/32 in lamina propria were inhibited after treatment with hydrogen, but the changes has no effects in other tissues. Hydrogen inhibited the NF-κB p65 in M1 macrophages nucleus and distal ileum of NEC. HE staining showed hydrogen could attenuate the severity of NEC.Conclusion: Hydrogen could attenuate the severity of NEC through promoting M1 macrophages conversion by inhibited the expression of NF-κB p65 in the nucleus.

Abstract Background Death anxiety is a common phenomenon in all societies. Older adults may be more prone to death anxiety than their younger counterparts; however, death anxiety among older adults is not well understood. This study explores the relationship between meaning in life, self-esteem, and death anxiety in senior citizens in China. Methods A total of 283 older adults participated in this study; data were collected via the Meaning in Life Questionnaire, the Rosenberg Self-Esteem Scale, and the Death Anxiety Scale. Results Results show that the dimensions of meaning in life, presence of meaning (r = − 0.43, p

Sarcoidosis is a systemic heterogeneous inflammatory disease; however, the etiology and pathogenesis of sarcoidosis are still unknown. Herein, we investigated the core microRNAs and potential molecular mechanisms in sarcoidosis. The DE-miRNAs were diagnosed using the LIMMA software package. DIANA-mirPath was employed to perform pathway and GO enrichment analysis of the DE-miRNAs. PPI networks and miRNA-target gene regulatory networks were used to obtain insight into the actions of DE-miRNAs. Expression of the hub genes along with miRNAs was validated in clinical specimens. Overall, 266 DE-miRNAs were screened. Among these DE-miRNAs, hsa-miR-144, hsa-miR-126, as well as hsa-miR-106a were the upmost upregulated miRNAs; hsa-miR-151-3p, hsa-miR-320d, and hsa-miR-324-3p were the top downregulated miRNAs. NR3C1, ZBTB7A, NUFIP2, BZW1, ERGIC2, and VEGFA were mapped as the most targeted hub genes in the upregulation of miRNAs, and MCL1 and SAE1 were the most targeted hub genes in the downregulation of miRNA. VEGFA and NR3C1 were selected and potentially modulated by hsa-miR-20b, hsa-miR-126, and hsa-miR-106a. In sarcoidosis pathological tissue, hsa-miR-126 was highly expressed, and VEGFA and NR3C1 were overexpressed. In conclusion, our results revealed the dysregulation of hsa-miR-126 and a potential regulatory mechanism for pathogenesis in sarcoidosis.

Glucocappasalin (GCP), a natural product derived from the seeds of Descurainia sophia (L.) Webb. ex Prantl, exhibits potential antitumor activity in HeLa cervical carcinoma cells. In this study, we investigated the anti-cervical cancer property of GCP through the induction of cell cycle arrest, apoptosis, and autophagy in vitro and in vivo, and elucidated the underlying molecular mechanisms. We demonstrated that treatment with GCP inhibited the growth of HeLa, Siha, and Ca Ski cell lines in a dose-dependent manner, with HeLa cells displaying particular sensitivity to the GCP treatment. Subsequently, the expression of cyclin-dependent kinase 1 (CDK1) and polo like kinase 1 (PLK1) were evaluated in HeLa cells using the CDK1 kinase assay kit, the fluorescence polarization assay, real-time quantitative PCR, and western blotting. Our results demonstrate that GCP could be employed to attenuate the expression of CDK1 and PLK1 in a dose- and time-dependent manner. The complementary results obtained by flow cytometry and western blotting allowed us to postulate that GCP may exhibit its antitumor effects by inducing G2/M cell cycle arrest. Moreover, HeLa cells treated with GCP exhibited a loss in mitochondrial membrane potential, together with the activation of caspases 3 and 9, and poly ADP-ribose polymerase (PARP). Additionally, we found that GCP could increase the formation of acidic vesicular organelles (AVOs), as well as the levels of Beclin1, LC3-II, p62, and Atg5 proteins in HeLa cells. Further studies indicated that GCP triggered autophagy via the suppression of the PI3K/AKT/mTOR signaling pathways. The autophagy inhibitor 3-methyladenine (3-MA) was used to determine whether autophagy affects the apoptosis induced by GCP. Interestingly, the inhibition of autophagy attenuated apoptosis. In vivo anti-tumor experiments indicated that GCP (60 mg/kg, i.p.) markedly reduced the growth of HeLa xenografts in nude mice without apparent toxicity. Taken together, we demonstrate that GCP induces cell cycle G2/M-phase arrest, apoptosis, and autophagy by acting on the PI3K/AKT/mTOR signaling pathways in cervical carcinoma cells. Thus, GCP may represent a promising agent in the eradication of cervical cancer.

Tumor cells circulating in the peripheral blood are the prime cause of cancer metastasis and death, thus the identification and discrimination of these rare cells are crucial in the diagnostic of cancer. As a label-free detection method without invasion, Raman spectroscopy has already been indicated as a promising method for cell identification. This study uses a confocal Raman spectrometer with 532 nm laser excitation to obtain the Raman spectrum of living cells from the kidney, liver, lung, skin, and breast. Multivariate statistical methods are applied to classify the Raman spectra of these cells. The results validate that these cells can be distinguished from each other. Among the models built to predict unknown cell types, the quadratic discriminant analysis model had the highest accuracy. The demonstrated analysis model, based on the Raman spectrum of cells, is propitious and has great potential in the field of biomedical for classifying circulating tumor cells in the future.

Toxoplasma gondii is a common opportunistic protozoan pathogen that can parasitize the karyocytes of humans and virtually all other warm-blooded animals. In the host’s innate immune response to T. gondii infection, inflammasomes can mediate the maturation of pro-IL-1β and pro-IL-18, which further enhances the immune response. However, how intercellular parasites specifically provoke inflammasome activation remains unclear. In this study, we found that the T. gondii secretory protein, rhoptry protein 7 (ROP7), could interact with the NACHT domain of NLRP3 through liquid chromatography-mass spectrometry analysis and co-immunoprecipitation assays. When expressing ROP7 in differentiated THP-1 cells, there was significant up-regulation in NF-κB and continuous release of IL-1β. This process is pyroptosis-independent and leads to inflammasome hyperactivation through the IL-1β/NF-κB/NLRP3 feedback loop. The loss of ROP7 in tachyzoites did not affect parasite proliferation in host cells but did attenuate parasite-induced inflammatory activity. In conclusion, these findings unveil that a T. gondii-derived protein is able to promote inflammasome activation, and further study of ROP7 will deepen our understanding of host innate immunity to parasites.

BackgroundNeuroimaging research has determined deficits in the dopaminergic circuit of major depressive disorder (MDD) during adolescence. This study investigated how emotional contexts modulate the temporal dynamics of reward anticipation and feedback in adolescents.MethodsEEG data from 35 MDD and 37 healthy adolescents were recorded when they conducted a gambling task after being presented with emotional pictures.ResultsThe results demonstrated that both MDD and healthy adolescents exhibited the largest late positive component (LPC) in positive contexts at the frontal sites and the largest LPC in negative contexts at the central sites; however, MDD adolescents exhibited anticipatory LPC hypoactivation than healthy adolescents. However, MDD adolescents exhibited smaller gain feedback negativity (FN) than healthy adolescents independent of emotional contexts, positively correlating with the trait anhedonia according to the consummatory aspect of the Temporal Experience of Pleasure Scale. In contrast, MDD adolescents exhibited greater FN loss in positive and neutral contexts than healthy adolescents while no difference in FN loss was found between the two groups in negative contexts. Moreover, the FN loss amplitudes negatively correlated with hedonic tone according to the Snaith-Hamilton Pleasure Scale over the past week.ConclusionsThese findings suggest that MDD adolescents exhibited dissociable deficits in reward anticipation and gain or loss feedback that are distinctly modulated by emotional contexts, and they deepen our understanding of the modulation of emotional contexts on the temporal dynamic reorganization of the reward circuit in MDD adolescents.

The production of cellulases in plants is an economical method for the conversion of lignocellulosic biomass into fuels. Herein we report the expressions of two thermostable Acidothermus cellulolyticus cellulases, endo-1,4-β-D-glucanase (E1) and exoglucanase (Gux1), in tobacco and rice. To evaluate the expression of these recombinant cellulases, we expressed the full-length E1, the catalytic domains of E1 (E1cd) and Gux1 (Gux1cd), as well as an E1–Gux1cd fusion enzyme in various subcellular compartments. In the case of tobacco, transgenic plants that expressed apoplast-localized E1 showed the highest level of activity, about three times higher than those that expressed the cytosolic E1. In the case of rice, the level of cellulase-specific activity in the transgenic plants ranged from 11 to 20 nmol 4-methylumbelliferone min−1 mg−1 total soluble protein. The recombinant cellulases exhibited good thermostability below 70 °C. Furthermore, transgenic rice leaves that were stored at room temperature for a month lost about 20% of the initial cellulase activity. Taken together, the results suggested that heterologous expression of thermostable cellulases in plants may be a viable option for biomass conversion.

Antimony trioxide (Sb2O3) micro- and nanomaterials have been widely used as a fire retardant, and are promising for fabricating high-performance cool materials and optoelectronic devices, but little is known on their mechanical properties. In this study, Young’s moduli of Sb2O3 micro- and nanowires grown via chemical vapor deposition are accurately determined by a nanomanipulation-assisted thermal resonance method. The Sb2O3 micro- and nanowires grow along the [001] direction and have irregular cross sections with thicknesses ranged from 87 to 238 nm and widths ranged from 168 to 549 nm. The measured Young modulus value is 92 ± 7 GPa, which is thickness independent and very close to the value of 89 GPa predicted using the first-principle calculations. The developed method can be extended for accurately measuring the Young’s modulus of any micro- and nanowire with irregular cross section.

Hirschsprung disease is a birth defect characterized by complete absence of neuronal ganglion cells from a portion of the intestinal tract. To uncover genetic variants contributing to HSCR, we performed whole exome sequencing on seven members of an HSCR family. With the minor allele frequency (MAF) calculated by gnomAD, we finally filtered a total of 1,059 rare variants in this family (MAF < 0.1%). With the mode of inheritance and pathogenicity scores by bioinformatics tools, we identified an in-frameshift variant p.Phe147del in RET as the disease-causing variant. Further analysis revealed that the in-frameshift variant may function by disrupting the glycosylation of RET protein. To our knowledge, this is the first study to report the in-frameshift variant p.Phe147del in RET responsible for heritable HSCR.

Cell trapping is a very useful technique in a variety of cell-based assays and cellular research fields. It requires a high-throughput, high-efficiency operation to isolate cells of interest and immobilize the captured cells at specific positions. In this study, a dentate spiral microfluidic structure is proposed for cell trapping. The structure consists of a main spiral channel connecting an inlet and an out and a large number of dentate traps on the side of the channel. The density of the traps is high. When a cell comes across an empty trap, the cell suddenly makes a turn and enters the trap. Once the trap captures enough cells, the trap becomes closed and the following cells pass by the trap. The microfluidic structure is optimized based on the investigation of the influence over the flow. In the demonstration, 4T1 mouse breast cancer cells injected into the chip can be efficiently captured and isolated in the different traps. The cell trapping operates at a very high flow rate (40 μL/s) and a high trapping efficiency (>90%) can be achieved. The proposed high-throughput cell-trapping technique can be adopted in the many applications, including rapid microfluidic cell-based assays and isolation of rare circulating tumor cells from a large volume of blood sample.

Purpose: The Ministry of Finance issued the new China accounting standards on February 15, 2006(CAS2006), which require the listed companies to use the balance sheet liability method for the income tax accounting. Thus, it give us an opportunity to investigate the earnings management of listed companies from the perspective of income tax. Under the balance sheet liability method, because conforming earnings management strategies and nonconforming earnings management strategies have different income tax cost and the current income payable will also vary, the listed companies need to choose conforming earnings management and nonconforming earnings management. Our research just try to investigate the relationship between the listed companies’ income tax planning and earnings management on the background of this new system.Design/methodology/approach: Our research approach combines theoretical analysis and empirical analysis. This paper first make a deep theoretical analysis on the listed companies’ choice between pretax earnings management activities that have current income tax consequences (book-tax ‘conforming earnings management’) and earnings management activities that do not have current income tax consequences (book-tax ‘nonconforming earnings management’),and then we exemplify our theory. Next, we come up with two hypotheses based on the theoretical analysis, build up a restatement model and conduct the empirical examination. The empirical analysis employs the method of descriptive statistics and logistic regression.Findings: When engaging in earnings management, listed companies will trade off conforming and nonconforming earnings management from the perspective of income tax cost. We find that managers’ motivations and purposes will influence the choice. On the one hand, when companies are facing the punishment of the suspension or termination of the listing for three consecutive losses, they will have a great incentive to manage earnings in order to turn losses into gains. In this case, companies can’t wait to manage earnings to increase incomes and won’t consider income tax cost too much. And if they employ nonconforming earnings management bringing greater book-tax differences, it may increase the probability of being detected and earnings management behavior may also be found. Thus, in this motivation, listed companies will employ more conforming earnings management. On the other hand, when companies engage in fraudulent activities, they will avoid the use of earnings management strategies which bringing greater book-tax difference to avoid penalty cost associating with fraud being found, since greater book-tax difference will possibly attract regulatory agencies’ and auditors’ attention therefore lead to the fraud being found. In this motivation, listed companies will employ more conforming earnings management. In summary, the main conclusion is when the company has motivations to turn losses into gains and has the motivation to avoid penalty cost associated with fraud being found, the company prefers to employ more conforming earnings management strategies.Research limitations/implications: The limitation in our research is as follows. First, we mainly focus on the conforming and nonconforming earnings management when the listed companies restate their financial statements. However after the issue of CAS2006, many listed companies still not disclose income tax account, which restrict our sample. Second, without the acquisition of private companies’ data, our empirical results may have some errors. We will solve these problems in our future study.Practical/social implications: Based on the sample of restatement companies, our research explores the listed companies’ choice of conforming and nonconforming earnings management under different motivations, which provides our study with new perspective and theoretical evidence. Meanwhile, because this paper focuses on restate firms’ earnings management, the results are helpful for regulators to strengthen the administration of listed companies’ restatement, as well as decrease the damage of restatement on our capital market. Finally, our results indicate that when the company has motivations to turn losses into gains and has motivations to avoid penalty cost associated with fraud being found, the company prefers to employ more conforming earnings management strategies. It will help us to deeply understand the impact of the accounting processes of income tax under the balance sheet liability method on the listed companies, therefore provide companies’ income tax planning with essential empirical and theoretical evidences.Originality/value: So far, earnings management researches in academia mostly focus on the cost, motivations, means and results of earnings management, there are few studies discuss the choice of earnings management strategies and how different purposes and motivations affect the choice from the perspective of income tax. The issue of CAS2006 offers an opportunity for this research. This paper use restatement as sample to investigate the choice of conforming earnings management and nonconforming earnings management under different motivations and purposes for the first time. And not only study the effect that earnings management have on income tax, but also study the effect of different earnings management motivations on the choice of earnings management strategies.

Basic fibroblast growth factor (bFGF) is a member of the fibroblast growth factor family that has effects on wounding healing and neuro-protection. However, it is difficult to use bFGF to treat diseases that are separated by physiological barriers, such as the dermal barrier and blood brain barrier.To improve bFGF's penetration ability, we fused the recombinant human fibroblast growth factor (rhbFGF) gene with TAT. We constructed a pET3c vector that contained the recombinant bFGF gene and successfully expressed this gene in the E. coli strain BL21 (DE3) pLsS. The fusion protein was purified using CM Sepharose FF and heparin affinity chromatography. The purity of the TAT-rhbFGF was greater than 95%, as detected by SDS-PAGE. An in vitro MTT trial revealed that the modified bFGF significantly promoted the proliferation of NIH3T3 cells. The cell penetration trial and the mouse skin penetration trial demonstrated that the fusion protein had certain penetration abilities. The animal experiments confirmed that TAT-rhbFGF was effective in the treatment of the hypertrophic scars.We have successfully expressed and purified a TAT-rhbFGF fusion protein in this study. Our results have shown that the fusion protein had a greater ability to penetrate the dermal skin layer. TAT-rhbFGF improved the physical appearance of hypertrophic scars. TAT-rhbFGF may be a potential fusion protein in the treatment of dermal disorders, including hypertrophic scar.

The definition of deep tissue injury was derived from multiple clinical cases as "A purple or maroon localized area of discolored intact skin or blood-filled blister due to damage of underlying soft tissue from pressure and/or shear". Acidic fibroblast growth factor (aFGF) significantly improves wound healing under diabetic conditions. However, to date, the therapeutic application of aFGF has been limited, due to its low delivery efficiency and short half-life.Using an animal model of magnet-induced pressure ulcers, transactivator of transcription protein (TAT)-aFGF was evaluated for transdermal delivery and wound healing. Immunohistochemistry and Western blotting were also performed to determine the expression of transforming growth factor (TGF)-β1, α-smooth muscle actin (α-SMA), CD68, proliferating cell nuclear antigen (PCNA) and TGF-β-receptor II (TGF- βRII) in cultured human dermal fibroblasts. We found that that mice treated with TAT-aFGF had higher accumulation of aFGF in both dermis and subcutaneous tissues compared with mice treated with aFGF alone. In the remodeling phase, TAT-aFGF treatment decreased the expression of α-SMA to normal levels, thereby facilitating normal wound healing processes and abrogating hypertrophic scarring. In human dermal fibroblasts, TAT-aFGF reversed the suppressive effect of TNF-α on α-SMA expression and restored TGF-βRII and TGF-β1 expression.Our results demonstrate that TAT-aFGF has a favorable therapeutic effect on the healing of subcutaneous deep tissue injury.

The current focus in the field of life science is the use of tissue engineering scaffolds to repair human organs, which has shown great potential in clinical applications. Extracellular matrix morphology and the performance and internal structure of natural organs are required to meet certain requirements. Therefore, integrating multiple processes can effectively overcome the limitations of the individual processes and can take into account the needs of scaffolds for the material, structure, mechanical properties and many other aspects. This study combined the biological 3D printing technology and the near-field electro-spinning (NFES) process to prepare a multi-scale controlled tissue engineering scaffold. While using 3D printing technology to directly prepare the macro-scaffold, the compositing NFES process to build tissue micro-morphology ultimately formed a tissue engineering scaffold which has the specific extracellular matrix structure. This scaffold not only takes into account the material, structure, performance and many other requirements, but also focuses on resolving the controllability problems in macro- and micro-forming which further aim to induce cell directed differentiation, reproduction and, ultimately, the formation of target tissue organs. It has in-depth immeasurable significance to build ideal scaffolds and further promote the application of tissue engineering.

We investigate the complete moment convergence for maximal partial sum of arrays of rowwise φ-mixing random variables under some more general conditions. The results obtained in the paper generalize and improve some known ones.

The factor of combustion and explosion remains one of the main constraints on coal mining and management. To clarify the impact of structural properties on the consequences of gas explosion disasters during coal mining, this article conducts a study on the impact of the elastic modulus of structures on gas explosion disasters. The research results indicate that in the case where structures with high elastic modulus must exist, the elastic modulus of the structure has minimal impact on the structure during the early stage of flame development. The area of flame front and the degree of deflagration also decrease with the increase of elastic modulus, but the disturbance degree of air-flow and flame in the pipe increases with the increase of elastic modulus. The peak flame velocity at elastic modulus of 0.7 GPa and 2.8 GPa increased by 3.56% and 7.47% compared to elastic modulus of 0.18 GPa, respectively. The upstream overpressure peak increased by 24.63% and 42.52%. The downstream overpressure peak increased by 11.19% and 20.62%. The peak values of flame velocity and overpressure increase with the increase of elastic modulus, while the explosion intensity and pressure rise rate increase with the increase of elastic modulus. The explosion intensity index at elastic modulus 2.8 GPa is approximately 1.45 times that at elastic modulus 0.18 GPa. Therefore, it is necessary to choose structures with smaller elastic modulus as much as possible to achieve the best fire and explosion suppression effect. [ABSTRACT FROM AUTHOR]

Based on the self-built experimental set-up, the propagation law of explosion flame of hydrogen/methane premixed gas with different hydrogen volume fractions in different equivalent ratios was investigated under the action of a corrugated fire-retardant core. The experimental study shows that the flame isolation and suppression effect of the corrugated fire-retardant core at different equivalence ratios is either promoted or suppressed, the hydrogen/methane premixed gas explosion flame is quenched without hydrogen mixing when ϕ = 0.8 and 1.0, and also quenched when ϕ = 1.2 in different hydrogen volume fractions. The corrugated flame-retardant core significantly affected the extinguishing of the explosion flame of the premixed gas when ϕ = 1.2, the flame propagation speed and overpressure showed a similar trend under different volume fractions of hydrogen. When the flame is quenched, the flame is depressed inward to form a reverse spherical cell flame, reverse diffusion combustion phenomenon occurs, and it lasts a long time, eventually, the combustion reaction extinguished. The flame penetrated the corrugated fire-retardant core during the rest of conditions. When ϕ = 1.0, the flame reaction of the hydrogen/methane premixed gas explosion under the action of the corrugated fire-retardant core is the most violent, and its propagation speed and overpressure jump rapidly until it reaches a peak. [ABSTRACT FROM AUTHOR]