Multi-strategy learning-based particle swarm optimization algorithm for COVID-19 threshold segmentation.

With advancements in science and technology, the depth of human research on COVID-19 is increasing, making the investigation of medical images a focal point. Image segmentation, a crucial step preceding image processing, holds significance in the realm of medical image analysis. Traditional threshold image segmentation proves to be less efficient, posing challenges in selecting an appropriate threshold value. In response to these issues, this paper introduces Inner-based multi-strategy particle swarm optimization (IPSOsono) for conducting numerical experiments and enhancing threshold image segmentation in COVID-19 medical images. A novel dynamic oscillatory weight, derived from the PSO variant for single-objective numerical optimization (PSOsono) is incorporated. Simultaneously, the historical optimal positions of individuals in the particle swarm undergo random updates, diminishing the likelihood of algorithm stagnation and local optima. Moreover, an inner selection learning mechanism is proposed in the update of optimal positions, dynamically refining the global optimal solution. In the CEC 2013 benchmark test, PSOsono demonstrates a certain advantage in optimization capability compared to algorithms proposed in recent years, proving the effectiveness and feasibility of PSOsono. In the Minimum Cross Entropy threshold segmentation experiments for COVID-19, PSOsono exhibits a more prominent segmentation capability compared to other algorithms, showing good generalization across 6 CT images and further validating the practicality of the algorithm.

Hyperthermia improves gemcitabine sensitivity of pancreatic cancer cells by suppressing the EFNA4/ß-catenin axis and activating dCK.

Background: Previously, our investigations have underscored the potential of hyperthermia to improve the therapeutic efficacy of gemcitabine (GEM) in pancreatic cancer (PC). Nonetheless, the precise underlying mechanisms remain elusive. Methods: We engineered two GEM-resistant PC cell lines (BxPC-3/GEM and PANC-1/GEM) and treated them with GEM alongside hyperthermia. The impact of hyperthermia on the therapeutic potency of GEM was ascertained through MTT assay, assessment of the concentration of its active metabolite dFdCTP, and evaluation of deoxycytidine kinase (dCK) activity. Lentivirus-mediated dCK silencing was further employed to validate its involvement in mediating the GEM-sensitizing effect of hyperthermia. The mechanism underlying hyperthermia-mediated dCK activation was explored using bioinformatics analyses. The interplay between hyperthermia and the ephrin A4 (EFNA4)/ß-catenin/dCK axis was investigated, and their roles in GEM resistance was further explored via the establishment of xenograft tumor models in nude mice. Results: Hyperthermia restored dCK expression in GEM-resistant cell lines, concurrently enhancing GEM sensitivity and fostering DNA damage and cell death. These observed effects were negated by dCK silencing. Regarding the mechanism, hyperthermia activated dCK by downregulating EFNA4 expression and mitigating ß-catenin activation. Overexpression of EFNA4 activated the ß-catenin while suppressing dCK, thus diminishing cellular GEM sensitivity-a phenomenon remediated by the ß-catenin antagonist MSAB. Consistently, in vivo, hyperthermia augmented the therapeutic efficacy of GEM on xenograft tumors through modulation of the ephrin A4/ß-catenin/dCK axis. Conclusion: This study delineates the role of hyperthermia in enhancing GEM sensitivity of PC cells, primarily mediated through the suppression of the EFNA4/ß-catenin axis and activation of dCK.

Development and validation of a novel 30-plex STR assay for canine individual identification and parentage testing.

Domestic dogs are helpers in outdoor human work and companions for families; thus, individual canine identification and parentage testing are crucial in certain fields, including forensics and breeding programs. In this study, a six-dye fluorescent labeling multiplex amplification system containing 29 canine short tandem repeats (STRs) and the sex-determining marker DAmel was developed. The system was called the Tronfo Canine 30-plex STR Kit and was further validated according to the Scientific Working Group on DNA Analysis Methods and the Organization of Scientific Area Committees for Wildlife Forensics guidelines, including tests for PCR conditions, precision, species specificity, sensitivity, stability, repeatability and reproducibility, a population study, and a study of 16 paternity test cases. The results indicated that the novel canine STR assay was accurate, specific, reproducible, stable, and robust. Complete profiles were obtained with 31.25 pg of canine DNA. Additionally, 500 unrelated canine individuals were investigated using this novel system, and the combined power of discrimination and exclusion values were 0.999999999999999999 and 0.999996451039850, respectively. These results suggest that the Tronfo Canine 30-plex STR Kit is highly polymorphic, informative, and suitable for individual canine identification and parentage testing.

Intravitreal Delivery of rAAV2-hSyn-hRS1 Results in Retinal Ganglion Cell-Specific Gene Expression and Retinal Improvement in the Rs1-KO Mouse.

X-linked retinoschisis (XLRS) is a monogenic recessive inherited retinal disease caused by defects in retinoschisin (RS1). It manifests clinically as retinal schisis cavities and a disproportionate reduction of b-wave amplitude compared with the a-wave amplitude. Currently there is no approved treatment. In the last decade, there has been major progress in the development of gene therapy for XLRS. Previous preclinical studies have demonstrated the treatment benefits of hRS1 gene augmentation therapy in mouse models. However, outcomes in clinical trials have been disappointing, and this might be attributed to dysfunctional assembly of RS1 complexes and/or the impaired targeted cells. In this study, the human synapsin 1 gene promoter (hSyn) was used to control the expression of hRS1 to specifically target retinal ganglion cells and our results confirmed the specific expression and functional assembly of the protein. Moreover, our results demonstrated that a single intravitreal injection of rAAV2-hSyn-hRS1 results in architectural restoration of retinal schisis cavities and improvement in vision in a mouse model of XLRS. In brief, this study not only supports the clinical development of the rAAV2-hSyn-hRS1 vector in XLRS patients but also confirms the therapeutic potential of rAAV-based gene therapy in inherited retinal diseases.

Integrated improved Harris hawks optimization for global and engineering optimization.

The original Harris hawks optimization (HHO) algorithm has the problems of unstable optimization effect and easy to fall into stagnation. However, most of the improved HHO algorithms can not effectively improve the ability of the algorithm to jump out of the local optimum. In this regard, an integrated improved HHO (IIHHO) algorithm is proposed. Firstly, the linear transformation escape energy used by the original HHO algorithm is relatively simple and lacks the escape law of the prey in the actual nature. Therefore, intermittent energy regulator is introduced to adjust the energy of Harris hawks, which is conducive to improving the local search ability of the algorithm while restoring the prey's rest mechanism; Secondly, to adjust the uncertainty of random vector, a more regular vector change mechanism is used instead, and the attenuation vector is obtained by modifying the composite function. Finally, the search scope of Levy flight is further clarified, which is conducive to the algorithm jumping out of the local optimum. Finally, in order to modify the calculation limitations caused by the fixed step size, Cardano formula function is introduced to adjust the step size setting and improve the accuracy of the algorithm. First, the performance of IIHHO algorithm is analyzed on the Computational Experimental Competition 2013 (CEC 2013) function test set and compared with seven improved evolutionary algorithms, and the convergence value of the iterative curve obtained is better than most of the improved algorithms, verifying the effectiveness of the proposed IIHHO algorithm. Second, the IIHHO is compared with another three state of the art (SOTA) algorithms with the Computational Experimental Competition 2022 (CEC 2022) function test set, the experiments show that the proposed IIHHO algorithm still has a strong ability to search for the optimal value. Third, IIHHO algorithm is applied in two different engineering experiments. The calculation results of minimum cost prove that IIHHO algorithm has certain advantages in dealing with the problem of search space. All these demonstrate that the proposed IIHHO is promising for numeric optimization and engineering applications.

CsiR-mediated signal transduction pathway in response to low iron conditions promotes Escherichia coli K1 invasion and penetration of the blood-brain barrier.

Escherichia coli K1 is the leading cause of neonatal Gram-negative bacterial meningitis, but the pathogenesis of E. coli K1 meningitis remains unclear. Blood-brain barrier (BBB) penetration is a crucial step in E. coli meningitis development. Here, we uncovered the crucial role of CsiR, a GntR family regulator, in E. coli K1 virulence. During infection, csiR expression was induced due to the derepression by Fur in the blood and human brain microvascular endothelial cells (HBMECs). CsiR positively regulated ilvB expression, which is associated with branched chain amino acid synthesis. Furthermore, we revealed that IlvB activated the FAK/PI3 K pathway of HBMECs to induce actin cytoskeleton rearrangements, thereby promoting the bacterial invasion and penetration of the BBB. Overall, this study reveals a CsiR-mediated virulence regulation pathway in E. coli K1, which may provide a useful target for the prevention or therapy of E. coli meningitis.

A multilocus DNA mini-barcode assay to identify twenty vertebrate wildlife species.

The world faces significant challenges in preserving the diversity of vertebrate species due to wildlife crimes. DNA barcoding, an effective molecular marker for insufficient nuclear DNA, is an authentic and quick identification technique to trace the origin of seized samples in forensic investigations. Here, we present a multiplex assay capable of identifying twenty vertebrate wildlife species utilizing twenty species-specific primers that target short fragments of the mitochondrial Cyt b, COI, 16S rRNA, and 12S rRNA genes. The assay achieved strong species specificity and sensitivity with a detection limit as low as 5 pg of DNA input. Additionally, it effectively discriminated a minor contributor (≥1%) from binary mixtures and successfully identified of noninvasive samples, inhibited DNA samples, artificially degraded DNA samples, and case samples, demonstrating a sensitive, robust, practical and easily interpretable tool in screening, and investigating forensic wildlife crimes.

Polyvinyl Alcohol-Citric Acid: A New Material for Green and Efficient Removal of Cationic Dye Wastewater.

The citric acid (CA) cross-linked polyvinyl alcohol (PVA) adsorbent, PVA-CA, was efficiently synthesized and its application to the removal of dyes in water, particularly the cationic dye, methylene blue (MB), was thoroughly investigated. The morphologies and physiochemical characteristics of PVA-CA were fully characterized by SEM, FT-IR, XRD, TGA, BET, and XPS. The effects of contact time, adsorbent dosage, MB concentration, solution pH, and temperature on the adsorption performance were compared using controllable methods. The maximum adsorption capacity of PVA-CA was 709.86 mg g-1 and the removal rate remained high through several adsorption-desorption cycles, demonstrating that such a composite absorbent has a good adsorption performance and recoverability. Further analysis by the density functional theory (DFT) showed that van der Waals interactions, electrostatic interactions and hydrogen bonding interactions between PVA-CA and MB played significant roles in the adsorption mechanism.

Different types of cell death in diabetic endothelial dysfunction.

Diabetes mellitus is a metabolic disease caused by disorders of insulin secretion and utilization. Long-term hyperglycemia, insulin resistance, and disorders of glucose and lipid metabolism cause vascular endothelial cell damage. Endothelial dysfunction is a key feature of diabetic vascular complications such as diabetic nephropathy, retinopathy, neuropathy, and atherosclerosis. Importantly, cell death is thought to be a key factor contributing to vascular endothelial injury. Morphologically, cell death can be divided into three forms: type I apoptosis, type II autophagy, and type III necrosis. According to the difference in function, cell death can be divided into accidental cell death (ACD) and regulated cell death (RCD). RCD is a controlled process involving numerous proteins and precise signaling cascades. Multiple subroutines covered by RCD may be involved in diabetic endothelial dysfunction, including apoptosis, autophagy, necroptosis, pyroptosis, entosis, ferroptosis, ferroautophagy, parthanatos, netotic cell death, lysosome-dependent cell death, alkaliptosis, oxeiptosis, cuproptosis, and PANoptosis. This article briefly reviews the mechanism and significance of cell death associated with diabetic endothelial dysfunction, which will help deepen the understanding of diabetic endothelial cell death and provide new therapeutic ideas.

How to promote the adoption of intelligent spray technology in farmers' cooperatives? --Based on the perspective of evolutionary game.

In order to accelerate the development of smart agriculture and realize the green transformation of agriculture, the coupling of prospect theory and evolutionary game theory is introduced. Construct a two-party evolutionary game model for the adoption of intelligent spray technology in farmers' cooperatives, analyze the evolution of farmers' cooperatives and government strategy selection and its influencing factors according to the replication dynamic equation, and conduct numerical simulation experiments through Matlab software. The results show that the adoption of intelligent spray technology by farmers' cooperatives and the government's choice of subsidies are the two optimal stable states of the evolutionary system. The government's subsidy policy can effectively stimulate farmers' cooperatives to adopt intelligent spray technology, but when the government subsidy coefficient is greater than or equal to 70%, the decision-making evolution of the government and farmers' cooperatives is unstable. The increase in farmers' awareness of pesticide hazards, the scale of operation of farmers' cooperatives, the price of high-quality agricultural products, and the sensitivity of farmers' cooperatives to profits and losses contribute to the promotion of intelligent spray technology, and the damage probability of intelligent spray technology has a restraining effect.

Developmental validation of a novel multiple genotyping assay with 24 Canine STR loci.

Canine individual identification and parentage testing are essential in various fields, including forensics and breeding programs. This study aimed to develop and validate the Canine 25 A kit, a multiplex polymerase chain reaction (PCR) system designed to address these critical requirements. This novel system enables the simultaneous amplification of 24 canine autosomal short tandem repeat (STR) loci and one sex-determining marker. Validation of the Canine 25 A kit was conducted following the Scientific Working Group on DNA Analysis Methods (SWGDAM) guidelines, demonstrating significant sensitivity, high inhibitor tolerance, canine specificity within a mixture, species specificity, and precision in genotype determination. The Canine 25 A kit was crucial in resolving several forensic cases, such as casework samples from a dog attack incident and parentage determination. Its effectiveness in genotyping these samples highlights its significance in forensic applications. Population genetic parameter analysis revealed a high discriminatory power, as indicated by the calculated combined discrimination power (CDP) values for each breed exceeding 0.999 999 999 999, while the combined power of exclusion (CPE) surpassed 0.9999. Overall, the Canine 25 A kit offers a precise and dependable tool for canine individual identification and parentage determination.

Pathogenic bacteria exploit transferrin receptor transcytosis to penetrate the blood-brain barrier.

The human blood-brain barrier (BBB) comprises a single layer of brain microvascular endothelial cells (HBMECs) protecting the brain from bloodborne pathogens. Meningitis is among the most serious diseases, but the mechanisms by which major meningitis-causing bacterial pathogens cross the BBB to reach the brain remain poorly understood. We found that Streptococcus pneumoniae, group B Streptococcus, and neonatal meningitis Escherichia coli commonly exploit a unique vesicle fusion mechanism to hitchhike on transferrin receptor (TfR) transcytosis to cross the BBB and illustrated the details of this process in human BBB model in vitro and mouse model. Toll-like receptor signals emanating from bacteria-containing vesicles (BCVs) trigger K33-linked polyubiquitination at Lys168 and Lys181 of the innate immune regulator TRAF3 and then activate the formation of a protein complex containing the guanine nucleotide exchange factor RCC2, the small GTPase RalA and exocyst subcomplex I (SC I) on BCVs. The distinct function of SEC6 in SC I, interacting directly with RalA on BCVs and the SNARE protein SNAP23 on TfR vesicles, tethers these two vesicles and initiates the fusion. Our results reveal that innate immunity triggers a unique modification of TRAF3 and the formation of the HBMEC-specific protein complex on BCVs to authenticate the precise recognition and selection of TfR vesicles to fuse with and facilitate bacterial penetration of the BBB.

Independent component analysis of Corynebacterium glutamicum transcriptomes reveals its transcriptional regulatory network.

Gene expression in bacteria is regulated by multiple transcription factors. Clarifying the regulation mechanism of gene expression is necessary to understand bacterial physiological activities. To further understand the structure of the transcriptional regulatory network of Corynebacterium glutamicum, we applied independent component analysis, an unsupervised machine learning algorithm, to the high-quality C. glutamicum gene expression profile which includes 263 samples from 29 independent projects. We obtained 87 robust independent regulatory modules (iModulons). These iModulons explain 76.7% of the variance in the expression profile and constitute the quantitative transcriptional regulatory network of C. glutamicum. By analyzing the constituent genes in iModulons, we identified potential targets for 20 transcription factors. We also captured the changes in iModulon activities under different growth rates and dissolved oxygen concentrations, demonstrating the ability of iModulons to comprehensively interpret transcriptional responses to environmental changes. In summary, this study provides a genome-scale quantitative transcriptional regulatory network for C. glutamicum and informs future research on complex changes in the transcriptome.

Hydrogen sulfide promoted retinoic acid-related orphan receptor α transcription to alleviate diabetic cardiomyopathy.

Diabetic cardiomyopathy (DCM) is one serious and common complication in diabetes without effective treatments. Hydrogen sulfide (H2S) fights against a variety of cardiovascular diseases including DCM. Retinoic acid-related orphan receptor α (RORα) has protective effects on cardiovascular system. However, whether RORα mediates the protective effect of H2S against DCM remains unknown. The present research was to explore the roles and mechanisms of RORα in H2S against DCM. The study demonstrated that H2S donor sodium hydrosulfide (NaHS) alleviated cell injury but enhanced RORα expression in high glucose (HG)-stimulated cardiomyocytes. However, NaHS no longer had the protective effect on attenuating cell damage and oxidative stress, improving mitochondrial membrane potential, inhibiting necroptosis and enhanced signal transducer and activator of transcription 3 (STAT3) Ser727 phosphorylation in HG-stimulated cardiomyocytes after RORα siRNA transfection. Moreover, NaHS improved cardiac function, attenuated myocardial hypertrophy and fibrosis, alleviated oxidative stress, inhibited necroptosis, but increased STAT3 phosphorylation in wild type (WT) mice but not in RORα knockout mice (a spontaneous staggerer mice, sg/sg mice) with diabetes. Additionally, NaHS increased RORα promoter activity in cardiomyocytes with HG stimulation, which was related to the binding sites of E2F transcription factor 1 (E2F1) in the upstream region of RORα promoter. NaHS enhanced E2F1 expression and increased the binding of E2F1 to RORα promoter in cardiomyocytes with HG stimulation. In sum, H2S promoted RORα transcription via E2F1 to alleviate necroptosis and protect against DCM. It is helpful to propose a novel therapeutic implication for DCM.

The application of 3D-printed auto-stable artificial vertebral body in en bloc resection and reconstruction of thoracolumbar metastases.

BACKGROUND: Nerve compression symptoms and spinal instability, resulting from spinal metastases, significantly impact the quality of life for patients. A 3D-printed vertebral body is considered an effective approach to reconstruct bone defects following en bloc resection of spinal tumors. The advantage of this method lies in its customized shape and innermost porous structure, which promotes bone ingrowth and leads to reduced postoperative complications. OBJECTIVE: The purpose of this study is to assess the effectiveness of 3D-printed auto-stable artificial vertebrae in the en bloc resection and reconstruction of thoracolumbar metastases. METHODS: This study included patients who underwent en bloc resection of thoracolumbar metastases based on the Weinstein-Boriani-Biagini surgical staging system, between January 2019 and April 2021. The patients were divided into two groups: the observation group, which was reconstructed using 3D-printed auto-stable vertebral bodies, and the control group, treated with titanium cages and allograft bone. Evaluation criteria for the patients included assessment of implant subsidence, instrumentation-related complications, VAS score, and Frankel grading of spinal cord injury. RESULTS: The median follow-up period was 21.8 months (range 12-38 months). Among the patients, 10 received a customized 3D-printed artificial vertebral body, while the remaining 10 received a titanium cage. The observation group showed significantly lower operation time, intraoperative blood loss, and postoperative drainage compared to the control group (P < 0.05). At the final follow-up, the average implant subsidence was 1.8 ± 2.1 mm for the observation group and 5.2 ± 5.1 mm for the control group (P < 0.05). The visual analog scale (VAS) scores were not statistically different between the two groups at preoperative, 24 h, 3 months, and 1 year after the operation (P < 0.05). There were no statistically significant differences in the improvements of spinal cord functions between the two groups. CONCLUSION: The utilization of a 3D-printed auto-stable artificial vertebra for reconstruction following en bloc resection of thoracolumbar metastases appears to be a viable and dependable choice. The low occurrence of prosthesis subsidence with 3D-printed prostheses can offer immediate and robust stability.

Neonatal Meningitis-Causing Escherichia coli Induces Microglia Activation which Acts as a Double-Edged Sword in Bacterial Meningitis.

Bacterial meningitis is a devastating disease occurring worldwide, with up to half of survivors left with permanent neurological sequelae. Neonatal meningitis-causing Escherichia coli (NMEC) is the most common Gram-negative bacillary organism that causes meningitis, particularly during the neonatal period. Here, RNA-seq transcriptional profiles of microglia in response to NMEC infection show that microglia are activated to produce inflammatory factors. In addition, we found that the secretion of inflammatory factors is a double-edged sword that promotes polymorphonuclear neutrophil (PMN) recruitment to the brain to clear the pathogens but, at the same time, induces neuronal damage, which may be related to the neurological sequelae. New neuroprotective therapeutic strategies must be developed for the treatment of acute bacterial meningitis. We found that transforming growth factor-ß (TGF-ß) may be a strong candidate in the treatment of acute bacterial meningitis, as it shows a therapeutic effect on bacterial-meningitis-induced brain damage. Prevention of disease and early initiation of the appropriate treatment in patients with suspected or proven bacterial meningitis are the key factors in reducing morbidity and mortality. Novel antibiotic and adjuvant treatment strategies must be developed, and the main goal for new therapies will be dampening the inflammatory response. Based on this view, our findings may help develop novel strategies for bacterial meningitis treatment.

Establishment and validation of a nomogram to predict the neck contracture after skin grafting in burn patients: A multicentre cohort study.

Cervical burn contracture is one of the burn contractures with the highest incidence and severity, and there is no effective method to predict the risk of neck contracture. This study aimed to investigate the effect of combined cervicothoracic skin grafting on the risk of neck contracture in burn patients and to develop a nomogram to predict the risk of neck contracture after skin grafting in burn patients. Data from 212 patients with burns who underwent neck skin grafting were collected from three hospitals, and the patients were randomly divided into training and validation sets. Independent predictors were identified through univariate and multivariate logistic regression analyses and incorporated into a prognostic nomogram. Its performance was assessed using the receiver operating characteristic area under the curve, calibration curve, and decision curve analysis. Burn depth, combined cervicothoracic skin grafting, graft thickness, and neck graft size were significantly associated with neck contractures. In the training cohort, the nomogram had an area under the curve of 0.894. The calibration curve and decision curve analysis indicated good clinical applicability of the nomogram. The results were tested using a validation dataset. Combined cervicothoracic skin grafting is an independent risk factor for neck contracture. Our nomogram demonstrated excellent performance in predicting neck contracture risk.

Development and application of a multiplex PCR system for forensic salivary identification.

In forensics, accurate identification of the origin of body fluids is essential for reconstructing a crime scene or presenting strong evidence in court. Microorganisms have demonstrated great potential in body fluid identification. We developed a multiplex PCR system for forensic salivary identification, which contains five types of bacteria:Streptococcus salivarius, Neisseria subflava, Streptococcus. mutans, Bacteroides thetaiotaomicron, and Bacteroides. uniformis. And the validated studies were carried out following the validation guidelines for DNA analysis methods developed by the Scientific Working Group on DNA Analysis Methods (SWGDAM), which included tests for sensitivity, species specificity, repeatability, stability, and mixed samples, trace samples, case samples, and a population study. Our result depicted that the lowest detection limit of the system was 0.01 ng template DNA. Moreover, the corresponding bacteria can still be detected when the amount of saliva input is low to 0.1 µL for DNA extraction. In addition, the target bacteria were not detected in the DNA of human, seven common animals, and seven bacteria DNA and in nine other body fluid samples (skin, semen, blood, menstrual blood, nasal mucus, sweat, tears, urine, and vaginal secretions). Six common inhibitors such as indigo, EDTA, hemoglobin, calcium ions, alcohol and humic acid were well tolerated by the system. What is more, the salivary identification system recognized the saliva component in all mixed samples and simulated case samples. Among 400 unrelated individuals from the Chinese Han population analyzed by this novel system, the detection rates of N. subflava, S. salivarius, and S. mutans were 97.75%, 70.75%, and 19.75%, respectively, with 100% identification of saliva. In conclusion, the salivary identification system has good sensitivity, specificity, stability, and accuracy, which can be a new effective tool for saliva identification.