Lipid A-modified Escherichia coli can produce porcine parvovirus virus-like particles with high immunogenicity and minimal endotoxin activity.

BACKGROUND: A cost-effective Escherichia coli expression system has gained popularity for producing virus-like particle (VLP) vaccines. However, the challenge lies in balancing the endotoxin residue and removal costs, as residual endotoxins can cause inflammatory reactions in the body. RESULTS: In this study, porcine parvovirus virus-like particles (PPV-VLPs) were successfully assembled from Decreased Endotoxic BL21 (BL21-DeE), and the effect of structural changes in the lipid A of BL21 on endotoxin activity, immunogenicity, and safety was investigated. The lipopolysaccharide purified from BL21-DeE produced lower IL-6 and TNF-α than that from wild-type BL21 (BL21-W) in both RAW264.7 cells and BALB/c mice. Additionally, mice immunized with PPV-VLP derived form BL21-DeE (BL21-DeE-VLP) showed significantly lower production of inflammatory factors and a smaller increase in body temperature within 3 h than those immunized with VLP from BL21-W (BL21-W-VLP) and endotoxin-removed VLP (ReE-VLP). Moreover, mice in the BL21-DeE-VLP immunized group had similar levels of serum antibodies as those in the BL21-W-VLP group but significantly higher levels than those in the ReE-VLP group. Furthermore, the liver, lungs, and kidneys showed no pathological damage compared with the BL21-W-VLP group. CONCLUSION: Overall, this study proposes a method for producing VLP with high immunogenicity and minimal endotoxin activity without chemical or physical endotoxin removal methods. This method could address the issue of endotoxin residues in the VLP and provide production benefits.

Adaptive prediction for effluent quality of wastewater treatment plant: Improvement with a dual-stage attention-based LSTM network.

The accurate effluent prediction plays a crucial role in providing early warning for abnormal effluent and achieving the adjustment of feedforward control parameters during wastewater treatment. This study applied a dual-staged attention mechanism based on long short-term memory network (DA-LSTM) to improve the accuracy of effluent quality prediction. The results showed that input attention (IA) and temporal attention (TA) significantly enhanced the prediction performance of LSTM. Specially, IA could adaptively adjust feature weights to enhance the robustness against input noise, with R2 increased by 13.18%. To promote its long-term memory ability, TA was used to increase the memory span from 96 h to 168 h. Compared to a single LSTM model, the DA-LSTM model showed an improvement in prediction accuracy by 5.10%, 2.11%, 14.47% for COD, TP, and TN. Additionally, DA-LSTM demonstrated excellent generalization performance in new scenarios, with the R2 values for COD, TP, and TN increasing by 22.67%, 20.06%, and 17.14% respectively, while the MAPE values decreased by 56.46%, 63.08%, and 42.79%. In conclusion, the DA-LSTM model demonstrated excellent prediction performance and generalization ability due to its advantages of feature-adaptive weighting and long-term memory focusing. This has forward-looking significance for achieving efficient early warning of abnormal operating conditions and timely management of control parameters.

Using Machine Learning and Finite Element Analysis to Extract Traction-Separation Relations at Bonding Wire Interfaces of Insulated Gate Bipolar Transistor Modules.

For insulated gate bipolar transistor (IGBT) modules using wire bonding as the interconnection method, the main failure mechanism is cracking of the bonded interface. Studying the mechanical properties of the bonded interface is crucial for assessing the reliability of IGBT modules. In this paper, first, shear tests are conducted on the bonded interface to test the bonded interface's strength. Then, finite element-cohesive zone modeling (FE-CZM) is established to describe the mechanical behavior of the bonded interface. A novel machine learning (ML) architecture integrating a convolutional neural network (CNN) and a long short-term memory (LSTM) network is used to identify the shape and parameters of the traction separation law (TSL) of the FE-CZM model accurately and efficiently. The CNN-LSTM architecture not only has excellent feature extraction and sequence-data-processing abilities but can also effectively address the long-term dependency problem. A total of 1800 sets of datasets are obtained based on numerical computations, and the CNN-LSTM architecture is trained with load-displacement (F-δ) curves as input parameters and TSL shapes and parameters as output parameters. The results show that the error rate of the model for TSL shape prediction is only 0.186%. The performance metric's mean absolute percentage error (MAPE) is less than 3.5044% for all the predictions of the TSL parameters. Compared with separate CNN and LSTM architectures, the proposed CNN-LSTM-architecture approach exhibits obvious advantages in recognizing TSL shapes and parameters. A combination of the FE-CZM and ML methods in this paper provides a promising and effective solution for identifying the mechanical parameters of the bonded interfaces of IGBT modules.

Recombination of Porcine Reproductive and Respiratory Syndrome Virus: Features, Possible Mechanisms, and Future Directions.

Recombination is a pervasive phenomenon in RNA viruses and an important strategy for accelerating the evolution of RNA virus populations. Recombination in the porcine reproductive and respiratory syndrome virus (PRRSV) was first reported in 1999, and many case reports have been published in recent years. In this review, all the existing reports on PRRSV recombination events were collected, and the genotypes, parental strains, and locations of the recombination breakpoints have been summarized and analyzed. The results showed that the recombination pattern constantly changes; whether inter- or intra-lineage recombination, the recombination hotspots vary in different recombination patterns. The virulence of recombinant PRRSVs was higher than that of the parental strains, and the emergence of virulence reversion was caused by recombination after using MLV vaccines. This could be attributed to the enhanced adaptability of recombinant PRRSV for entry and replication, facilitating their rapid propagation. The aim of this paper was to identify common features of recombinant PRRSV strains, reduce the recombination risk, and provide a foundation for future research into the mechanism of PRRSV recombination.

Antigenicity, epitope mapping, and intracellular distribution of the NSP7α protein of porcine reproductive and respiratory syndrome virus.

Porcine reproductive and respiratory syndrome virus (PRRSV) is an important pathogen that causes huge economic losses to the global pig industry. Nonstructural protein 7α (NSP7α) of PRRSV is highly conserved among different lineages of PRRSV and could be a potential target for the development of detection methods. In this study, NSP7α was expressed in prokaryote (Escherichia coli) and purified. An NSP7α-ab-ELISA detection method was established, the NSP7α-ab-ELISA has 93.1 % coincidence rate with IDEXX PRRS X3 ab test kit. NSP7α antibody was detected in pig serum by ELISA 14 days following PRRSV infection. Three monoclonal antibodies (4H9, 3F2, and C10) against NSP7α prepared by a hybridoma technique were used for epitope mapping by indirect immunofluorescence. The 4H9, 3F2, and C10 antibodies all recognized the C-terminal 72-149 amino acid region of NSP7α. 4H9 reacted with amino acids 135-143, but 3F2 and C10 did not react with any truncated polypeptide. In addition, by using the monoclonal antibodies, NSP7α was localized solely in the cytoplasm, while the N protein was distributed in the cytoplasm and nucleus. The collective findings of the antigenicity and epitope of NSP7α will be helpful for understanding the antigenicity of NSP7α and developing PRRSV diagnostic methods.

N6-methyladenosine modification of hypoxia-inducible factor-1α regulates Helicobacter pylori-associated gastric cancer via the PI3K/AKT pathway.

BACKGROUND: Helicobacter pylori (H. pylori) colonizes the human gastric mucosa and is implicated in the development of gastric cancer (GC). The tumor microenvironment is characterized by hypoxia, where hypoxia-inducible factor-1α (HIF-1α) plays a key role as a transcription factor, but the mechanisms underlying H. pylori-induced HIF-1α expression and carcinogenesis remain unclear. AIM: To explore the underlying mechanism of H. pylori-induced HIF-1α expression in promoting the malignant biological behavior of gastric epithelial cells (GES-1). METHODS: The study was conducted with human GES-1 cells in vitro. Relative protein levels of methyltransferase-like protein 14 (METTL14), HIF-1α, main proteins of the PI3K/AKT pathway, epithelial-mesenchymal transition (EMT) biomarkers, and invasion indicators were detected by Western blot. Relative mRNA levels of METTL14 and HIF-1α were detected by quantitative reverse transcription-polymerase chain reaction. mRNA stability was evaluated using actinomycin D, and the interaction between METTL14 and HIF-1α was confirmed by immunofluorescence staining. Cell proliferation and migration were evaluated by cell counting kit-8 assay and wound healing assay, respectively. RESULTS: H. pylori promoted HIF-1α expression and activated the PI3K/AKT pathway. Notably, METTL14 was downregulated in H. pylori-infected gastric mucosal epithelial cells and positively regulated HIF-1α expression. Functional experiments showed that the overexpression of HIF-1α or knockdown of METTL14 enhanced the activity of the PI3K/AKT pathway, thereby driving a series of malignant transformation, such as EMT and cell proliferation, migration, and invasion. By contrast, the knockdown of HIF-1α or overexpression of METTL14 had an opposite effect. CONCLUSION: H. pylori-induced underexpression of METTL14 promotes the translation of HIF-1α and accelerates tumor progression by activating the PI3K/AKT pathway. These results provide novel insights into the carcinogenesis of GC.

Fine-tuning DETR: Toward holistic process in plastic waste sorting system.

Every year human discharges about 350 million tons of plastic waste into the environment and can be projected to triple in 2060 without any attempts to change situation. From 1970 to 2019, an estimation of 130 million tons of plastic waste was accumulated into the rivers, lakes and sea, while only 27 % is recycled and utilized. Moreover, waste treatment plants in most places around the world are using out-of-date technology, may pose a threat to the health of the workers. Therefore, it is essential to modernize these systems for protecting human health. This paper proposes fine-tuning DETR, which applies Artificial Intelligent in plastic waste sorting system. Consequently, this study analyzed the applicability of fine-tuning DETR in the domain of plastic waste categorization and its potential drawbacks. For fair experiment and evaluation, model candidates were trained and evaluated on an industrial plastic waste dataset. The fine-tuning DETR outperformed other candidates in the context of critical indicators, from accuracy (25.1 mAP), processing speed (28 FPS) to computational cost (GFLOPs 86). Furthermore, fine-tuning DETR possesses the capability of autonomous operation without requiring human intervention, distinguishing this candidate from other prevalent algorithms. Our research demonstrates that, fine-tuning DETR specifically and Transformer-based algorithms in general, are entirely suitable and hold significant potential for large-scale application in holistic plastic waste sorting systems.

Minor envelope proteins from GP2a to GP4 contribute to the spread pattern and yield of type 2 PRRSV in MARC-145 cells.

In China, porcine reproductive and respiratory syndrome virus (PRRSV) vaccines are widely used. These vaccines, which contain inactivated and live attenuated vaccines (LAVs), are produced by MARC-145 cells derived from the monkey kidney cell line. However, some PRRSV strains in MARC-145 cells have a low yield. Here, we used two type 2 PRRSV strains (CH-1R and HuN4) to identify the genes responsible for virus yield in MARC-145 cells. Our findings indicate that the two viruses have different spread patterns, which ultimately determine their yield. By replacing the viral envelope genes with a reverse genetics system, we discovered that the minor envelope proteins, from GP2a to GP4, play a crucial role in determining the spread pattern and yield of type 2 PRRSV in MARC-145 cells. The cell-free transmission pattern of type 2 PRRSV appears to be more efficient than the cell-to-cell transmission pattern. Overall, these findings suggest that GP2a to GP4 contributes to the spread pattern and yield of type 2 PRRSV.

Strain to shine: stretching-induced three-dimensional symmetries in nanoparticle-assembled photonic crystals.

Stretching elastic materials containing nanoparticle lattices is common in research and industrial settings, yet our knowledge of the deformation process remains limited. Understanding how such lattices reconfigure is critically important, as changes in microstructure lead to significant alterations in their performance. This understanding has been extremely difficult to achieve due to a lack of fundamental rules governing the rearrangements. Our study elucidates the physical processes and underlying mechanisms of three-dimensional lattice transformations in a polymeric photonic crystal from 0% to over 200% strain during uniaxial stretching. Corroborated by comprehensive experimental characterizations, we present analytical models that precisely predict both the three-dimensional lattice structures and the macroscale deformations throughout the stretching process. These models reveal how the nanoparticle lattice and matrix polymer jointly determine the resultant structures, which breaks the original structural symmetry and profoundly changes the dispersion of photonic bandgaps. Stretching induces shifting of the main pseudogap structure out from the 1st Brillouin zone and the merging of different symmetry points. Evolutions of multiple photonic bandgaps reveal potential optical singularities shifting with strain. This work sets a new benchmark for the reconfiguration of soft material structures and may lay the groundwork for the study of stretchable three-dimensional topological photonic crystals.

MARCH8 inhibits pseudorabies virus replication by trapping the viral cell-to-cell fusion complex in the trans-Golgi network.

The membrane-associated RING-CH 8 protein (MARCH8), a member of the E3 ubiquitin ligase family, has broad-spectrum antiviral activity. However, some viruses hijack MARCH8 to promote virus replication, highlighting its dual role in the viral lifecycle. Most studies on MARCH8 have focused on RNA viruses, leaving its role in DNA viruses largely unexplored. Pseudorabies virus (PRV) is a large DNA virus that poses a potential threat to humans. In this study, we found that MARCH8 inhibited PRV replication at the cell-to-cell fusion stage. Interestingly, our findings proved that MARCH8 blocks gB cleavage by recruiting furin but this activity does not inhibit viral infection in vitro. Furthermore, we confirmed that MARCH8 inhibits cell-to-cell fusion independent of its E3 ubiquitin ligase activity but dependent on the interaction with the cell-to-cell fusion complex (gB, gD, gH, and gL). Finally, we discovered that the distribution of the cell-to-cell fusion complex is significantly altered and trapped within the trans-Golgi network. Overall, our results indicate that human MARCH8 acts as a potent antiviral host factor against PRV via trapping the cell-to-cell fusion complex in the trans-Golgi network.

MARCH1 and MARCH2 inhibit pseudorabies virus replication by trapping the viral cell-to-cell fusion complex in trans-Golgi network.

The membrane-associated RING-CH (MARCH) family of proteins are members of the E3 ubiquitin ligase family and are essential for a variety of biological functions. Currently, MARCH proteins are discovered to execute antiviral functions by directly triggering viral protein degradation or blocking the furin cleavage of viral class I fusion proteins. Here, we report a novel antiviral mechanism of MARCH1 and MARCH2 (MARCH1/2) in the replication of Pseudorabies virus (PRV), a member of the Herpesviridae family. We discovered MARCH1/2 restrict PRV replication at the cell-to-cell fusion step. Furthermore, MARCH1/2 block gB cleavage, and this is dependent on their E3 ligase activity. Interestingly, the blocking of gB cleavage by MARCH1/2 does not contribute to their antiviral activity in vitro. We discovered that MARCH1/2 are associated with the cell-to-cell fusion complex of gB, gD, gH, and gL and trap these viral proteins in the trans-Golgi network (TGN) rather than degrading them. Overall, we conclude that MARCH1/2 inhibit PRV by trapping the viral cell-to-cell fusion complex in TGN.

Effect of Portulacae Herba free granuleson integrin-β1 of rats’ lens with diabetic cataract / 国际中医中药杂志

Objective:To investigate the effect of Portulacae Herba free granules on the degree of lens opacity and integrin β1 of lens in diabetic cataract rats. Methods:50 rats were randomly divided into control group, model group and the low, medium and high dose group of Portulacae Herba, 10 rats in each group. Except the control group, the diabetic cataract rat model was established by intraperitoneal injection of 1% STZ 60 mg/kg. The low, medium and high dose groups of Portulacae Herba were gavaged with Portulacae Herba 125, 250, 500 mg/kg, once a day for 12 weeks. The degree of lens opacity was observed with slit lamp. After 12 weeks, the lens was stained with HE. The expression of integrin β1 was detected by Western blot.Results:Compared with the model group, the opacification degree of lens in the low, medium and high dose groups of Portulacae Herba was significantly decreased ( P<0.05), the expression of integrin β1 (1.58 ± 0.14, 1.46 ± 0.24, 1.12 ± 0.19 vs. 1.76 ± 0.23) in rat lens was decreased ( P<0.05). Conclusion:For diabetic cataract rats, Portulacae Herba free granules can influence the expression of integrin β1 and inhibit the occurance of lens opacity.

Predictive value of ODI, SBI and SF-36 in patients with recurrent lumbar disc herniation undergoing reoperation / 中国骨伤

OBJECTIVE@#To evaluate the predictive value of ODI, SBI and SF-36 in patients with recurrent lumbar disc herniation undergoing reoperation.@*METHODS@#The patients of recurrent lumbar disc herniation underwent surgical treatment from June 2013 to December 2015 were enrolled in the study. Patients were assigned to A, B, C groups according to the excellent, good, poor of clinical efficacy, and divided into training set and test set by 70:30 ratio according to random number table. we use ordered Logistic regression to construct prediction model, and test set to verify the effect of the model and calculate the accuracy of the model.@*RESULTS@#Both ODI and SBI were lower in group A and group B than group C, and the SF-36 scale was significantly higher than group C (<0.05). The predictive efficacy model by ordered Logistic regression construction showed that the ODI coefficient was 0.67, the SF-36 coefficient was -0.43, and the SBI coefficient was 0.52. In the group A with excellent clinical efficacy, the prediction accuracy rate of the model was 80%; in the group B with good clinical efficacy, the prediction accuracy rate was 76.92% and in the group C with poor clinical efficacy, the prediction accuracy rate was 44.44%.@*CONCLUSIONS@#Comprehensive consideration of ODI, SBI and SF-36 to construct a clinical prediction model for patients with recurrent intervertebral disc herniation after surgery can better predict patients' prognosis. It has a value for clinical application.

Clinical Characteristics of Brucellosis Complicated by Syndrome of Inappropriate Secretion of Antidiuresis / 中国医学科学院学报

To summarize and analyze the causes of hyponatremia in patients with brucellosis and explore the clinical manifestations of syndrome of inappropriate antidiuresis(SIAD)in patients with brucellosis. The clinical data of 111 patients with acute brucellosis who were treated in Peking Union Medical College Hospital from September 2011 to December 2017 were retrospectively reviewed.Hyponatremia was defined by serum sodium level lower than 135 mmol/L.Clinical characteristics including medical histories,vital signs,and laboratory test findings were collected and analyzed. Hyponatremia was found in 14(12.6%)of 111 patients with brucellosis,among whom 3 patients were confirmed to be with SIAD,10 were suspected as SIAD,and 1 was diagnosis as hypopituitarism.Hypoalbuminemia,elevation of erythrocyte sedimentation rate,and high sensitivity C reactive protein were found in brucellosis patients with SIAD,along with severe complications such as infective endocarditis,septic shock,and anemia. Hyponatremia is not a rare condition in brucellosis patients and may be caused by SIAD.

Clinical character and genetic mutation of 64 patients with Gitelman syndrome / 基础医学与临床

Objective To study the clinical and genetic profile of the patients with Gitelman syndrome ( GS ) . Methods We retrospectively analyzed the gene mutation and clinical character of 64 GS patients diagnosed in Pe-king Union Medical College Hospital from 2012 to 2016 .Results The age at diagnosis of these 64 patients ( 39 male,25 female) were (35±14) years.At admission, the serum potassium level of the patients was (2.86± 0.44) mmol/L, serum magnesium level was ( 0.62 ±0.14 ) mmol/L, 24-hour urine potassium was ( 82.27 ± 39.73)mmol/day, 24-hour urine calcium was (0.94±0.83)mmol/day and their average blood pressure was 110/69 mmHg.The gene mutation were divided into four groups including homozygous mutation ( n=5) , compound het-erozygous mutation(n=40), multiple mutations (n=9) and single heterozygous mutation (n=10) group.The compound heterozygous group had higher serum potassium concentration ( P<0.05 ) and the homozygous group had a relatively higher serum magnesium concentration but without significance .A total of 74 distinctly different mutation alleles were identified , of which 24 were new mutation alleles .p.Asp486Asn was a hotspot in our series which was found in 16 patients ( 25.0%) .Conclusions There exists great heterogeneity of gene mutation and clini-cal character in Gitelman syndrome .Patients with compound heterozygous have a relatively milder clinical character.p.Asp486Asn mutation is a hotspot in Chinese patients .

Study on correlation between neuropsychological features and Chinese medical syndrome types in patients with Wilson's disease / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the correlation between neuropsychological features and Chinese medical syndrome types in Wilson's disease (WD) patients, thus providing evidence for early intervention by syndrome typing.</p><p><b>METHODS</b>Totally 96 WD patients were assigned to Gan-Dan damp-heat syndrome (GDDHS, 31 cases), Gan-Shen yin deficiency syndrome (GSYDS, 47 cases), and qi-blood deficiency syndrome (QBDS, 18 cases) by syndrome typing. Three items of neuropsychological testing were performed in them, i.e., Raven's standard progressive matrices (R'SPM), Stroop color-word test (CWT), trail making test (TMT). The correlations between the integrals of Chinese medical syndrome types and results of the 3 tests were analyzed.</p><p><b>RESULTS</b>(1) There was statistical difference in the total scores of R'SPM, the word interference time of CWT, and interference effects of TMT among the 3 syndrome types (P <0.01, P <0.05). There was statistical difference in the total scores of R'SPM and the word interference time of CWT in patients of QBDS, when compared with those of GDDHS and GSYDS (P <0.05). There was statistical difference in interference effects of TMT in patients of GDDHS, when compared with those of QBDS and GSYDS (P <0.05). (2) The integrals of the 3 syndrome types were negatively correlated with the total scores of R'SPM (P <0.01). The integral of GDDHS was significantly positively correlated with the interference effects of TMT (P <0.01). The integral of GSYDS was significantly positively correlated with TMT-B time consumption and interference effects of TMT (P <0. 05). The integral of QBDS was significantly positively correlated with the word interference time of CWT (P <0.05).</p><p><b>CONCLUSIONS</b>There was correlation between neuropsychological changes of WD patients and Chinese medical syndrome types. The severity of asthenia syndrome was sequenced from high to low as QBDS > GSYDS > GDDHS. The severity of asthenia was higher than that of asthenia.</p>

Therapeutic Effect of Puerain with Corticosteroid on Nonanterior Ischmic Optic Neuropathy / 浙江中医药大学学报

[Objective] To observe the therapeutic effect of puerain with corticosteroid on nonanterior ischmic optic neuropathy (NAION).[Methods] In 58 patients(60 eyes)who were diagnosed as NA10N,29 patients (30 eyes)underwent intravenous drip with puerain and corticosteroid (treatment group);and the other 29 patients (3o eyes)underwent intravenous drip with corticosteroid and compound anisondine (control group).[Results] The visual acuity was better in treatment group than that in control group with a significant difference (x2=4.83,P