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ABSTRACT: Objectives: The emergence and outbreak of carbapenem-resistant Pseudomonas aeruginosa are a major global public threat. In this study we aimed to characterize the genome of drug-resistant and virulent genes in an extremely drug-resistant (XDR) P. aeruginosa strain to understand its antimicrobial resistance trends and pathogenicity. Methods: An XDR P. aeruginosa strain was isolated in China from a patient with severe pneumonia. Antimicrobial susceptibility testing, genome sequencing, and phylogenetic analysis were performed. Predictions were fulfilled using curated bioinformatics tools. Results: Assembly of the strain (CRPA190) comprised 76 contigs with a total length of 7 009 318 bp. CRPA190 belongs to sequence type 1971 (ST1971) and the O11 serogroup. Nine prophage regions, three CRISPR arrays, and two Cas clusters were identified. However, no plasmids were predicted. Antibiotic susceptibility tests showed that CRPA190 was resistant to all the tested antibiotics, including carbapenem, polymyxin B, and ceftazidime-avibactam. Forty antimicrobial resistance genes were predicted in CRPA190, including several carbapenemase genes such as blaPDC-142, blaPME-1, blaNDM-1, and blaOXA-902. The isolate was predicted to be pathogenic and possess strong biofilm-forming ability. It harbours virulence genes that are associated with an arsenal of virulence determinants involved in adherence, motility, exotoxins, exoenzymes, immune modulation, biofilms, nutritional/metabolic factors, and effector delivery systems. Conclusions: These findings enhance our understanding of the resistance and pathogenicity of the ST1971 P. aeruginosa strain that is unique in China and provide a broader perspective on the global epidemiological landscape, suggesting the emergence of P. aeruginosa ST1971, which requires control measures to limit its dissemination.

Abstract Background Depression is often linked to inflammation in the brain. Researchers have been exploring ways to reduce this inflammation to improve depression symptoms. One potential target is a protein called RIPK1, which is known to contribute to brain inflammation. However, it’s unclear how RIPK1 influences depression. Our study aims to determine whether RIPK1 inhibition could alleviate neuroinflammation-associated depression and elucidate its underlying mechanisms. Methods To investigate our research objectives, we established a neuroinflammation mouse model by administering LPS. Behavioral and biochemical assessments were conducted on these mice. The findings were subsequently validated through in vitro experiments. Results Using LPS-induced depression models, we investigated RIPK1’s role, observing depressive-like behaviors accompanied by elevated cytokines, IBA-1, GFAP levels, and increased inflammatory signaling molecules and NO/H2O2. Remarkably, Necrostatin (Nec-1 S), a RIPK1 inhibitor, mitigated these changes. We further found altered expression and phosphorylation of eIF4E, PI3K/AKT/mTOR, and synaptic proteins in hippocampal tissues, BV2, and N2a cells post-LPS treatment, which Nec-1 S also ameliorated. Importantly, eIF4E inhibition reversed some of the beneficial effects of Nec-1 S, suggesting a complex interaction between RIPK1 and eIF4E in LPS-induced neuroinflammation. Moreover, citronellol, a RIPK1 agonist, significantly altered eIF4E phosphorylation, indicating RIPK1’s potential upstream regulatory role in eIF4E and its contribution to neuroinflammation-associated depression. Conclusion These findings propose RIPK1 as a pivotal mediator in regulating neuroinflammation and neural plasticity, highlighting its significance as a potential therapeutic target for depression.

Programmed cell death(PCD)is a unique cell death involving effector molecules, including various forms such as apoptosis, autophagy, and pyroptosis. PCD is involved in many aspects of normal physiological activities in humans, and is closely related to the development of many diseases. Glaucoma is the leading cause of irreversible blindness worldwide. Relevant studies have shown that the development of glaucoma is associated with the abnormal expression of a variety of PCD-related proteins. The mechanism and interplay of apoptosis, autophagy, pyroptosis, ferroptosis and parthanatos of retinal ganglion cells in the course of glaucoma were reviewed, to provide a new direction for the prevention treatment of glaucoma.

Protein glycosylation is a type of protein post-translational modification. One specific example is the modification of proteins with O-linked β-N-acetylglucosamine (O-GlcNAc) and O-linked α-N-acetylgalactosamine (O-GalNAc). Enhanced levels of both O-GalNAc and O-GlcNAc in bladder cancer (BlCa) have been reported previously. However, the interplay between O-GalNAc and O-GlcNAc has yet to be explored. Herein, we find that the expression level of core1 β-1,3-galactosyltransferase (C1GalT1), which is responsible for extending and maturing mucin-type O-glycans, is increased in BlCa. This increase is accompanied by O-GlcNAc modification of C1GalT1. This modification stabilizes C1GalT1 expression and strengthens its interaction with its chaperone Cosmc. Mutation at Thr229 or Thr233 attenuates C1GalT1 stability and facilitates its degradation via the proteasome pathway. Furthermore, a decrease in C1GalT1 inhibits the pro-tumorigenic effect on bladder cancer cells by suppressing glycolysis.

Abstract Backgroud Type II congenital pulmonary airway malformation (CPAM) is a rare pulmonary microcystic developmental malformation. Surgical excision is the primary treatment for CPAM, although maternal steroids and betamethasone have proven effective in reducing microcystic CPAM. Disturbed intercellular communication may contribute to the development of CPAM. This study aims to investigate the expression profile and analyze intercellular communication networks to identify genes potentially associated with type II CPAM pathogenesis and therapeutic targets. Methods RNA sequencing (RNA-seq) was performed on samples extracted from both the cystic area and the adjacent normal tissue post-surgery in CPAM patients. Iterative weighted gene correlation network analysis (iWGCNA) was used to identify genes specifically expressed in type II CPAM. Single-cell RNA-seq (scRNA-seq) was integrated to unveil the heterogeneity in cell populations and analyze the communication and interaction within epithelial cell sub-populations. Results A total of 2,618 differentially expressed genes were identified, primarily enriched in cilium-related biological process and inflammatory response process. Key genes such as EDN1, GPR17, FPR2, and CHRM1, involved in the G protein-coupled receptor (GPCR) signaling pathway and playing roles in cell differentiation, apoptosis, calcium homeostasis, and the immune response, were highlighted based on the protein-protein interaction network. Type II CPAM-associated modules, including ciliary function-related genes, were identified using iWGCNA. By integrating scRNA-seq data, AGR3 (related to calcium homeostasis) and SLC11A1 (immune related) were identified as the only two differently expressed genes in epithelial cells of CPAM. Cell communication analysis revealed that alveolar type 1 (AT1) and alveolar type 2 (AT2) cells were the predominant communication cells for outgoing and incoming signals in epithelial cells. The ligands and receptors between epithelial cell subtypes included COLLAGEN genes enriched in PI3K-AKT singaling and involved in epithelial to mesenchymal transition. Conclusions In summary, by integrating bulk RNA-seq data of type II CPAM with scRNA-seq data, the gene expression profile and critical signaling pathways such as GPCR signaling and PI3K-AKT signaling pathways were revealed. Abnormally expressed genes in these pathways may disrupt epithelial-mesenchymal transition and contribute to the development of CPAM. Given the effectiveness of prenatal treatments of microcystic CPAM using maternal steroids and maternal betamethasone administration, targeting the genes and signaling pathways involved in the development of CPAM presents a promising therapeutic strategy.

Abstract To explore the multiparameter precursor characteristics of pre- and post-coal burst. Based on a coal burst of LW 1305 in the Zhaolou Coal Mine, an early warning method combining stress‒strain curve and microseismic multiparameter is proposed. The research results show that coal burst was induced by the intrinsic static high-stress concentration and the strong external impact loading generated by fracturing of the key stratum. The precursors mainly characterize the enhancement trend of the S value, the sudden and sharp increase in the A(t) value, the continuous and abnormal decrease in the b value, the increasing absolute value of Z sharply and larger than 2, the continuous and abnormal decrease in the Qt value, and the dominant frequency moving to the low-frequency band. Essentially, many micro-fissures inside the key stratum initiated, converged and connected to form macro-fractures, which was verified by the attenuation rate of the K value. Considering the time-varying effect of the overlying stratum movement, the curves of the six parameters agree well with those of stress vs. strain, which indicates that it is reasonable to take the observed zone as a whole system to investigate the variation in the multiple parameters and fracturing of the key stratum. The research results can be applied to the monitoring, early warning and control of coal burst so that effective safety measures can be taken in real time.

The effects of partitioning temperature and time on the strengthening and plasticising mechanism of a one-step quenching and partitioning (Q&P) steel were investigated. The results show that as the partitioning temperature decreased, the lath martensite became finer with higher dislocation density, while the dislocation density and RA amount decreased with increasing partitioning time. Lower quenching temperature and shorter partitioning time are conducive to achieve the high ultimate tensile strength of 1377 MPa and the better total elongation of 12.3% for low-carbon one-step Q&P steels. Meanwhile, the dislocation strengthening caused by martensite and the solid solution strengthening are main strengthening mechanisms of one-step Q&P steels. In addition, a new martensite transformation kinetic model considering the influence of silicon element was established, and simultaneously, the modified CCE model predicted RA fractions more accurately for high-silicon Q&P steels, especially at lower quenching temperature.

Robot integrated joints are extensively employed in the fields of medical and collaborative robots, and their friction characteristics are the crucial factors that affect robot performance. To improve the accuracy of the friction model, a hybrid friction modeling method integrating the mechanistic model and ensemble learning is proposed herein. First, the mechanistic model is developed based on the comprehensive analysis of various factors influencing joint friction and its periodic fluctuation. Assuming that the viscous friction and flow rate of lubricants are linear, the Stribeck model is used to describe the relationship between friction torque and motor velocity. Meanwhile, the Fourier series is used to model the periodic fluctuation of joint friction with the motor angle. The main harmonic components of the fluctuating friction torque are concentrated in the low frequency range. Considering the high frequency components will increase the complexity of the model, while the accuracy improvement of the parameterized model is limited. Therefore, the high-frequency components of the fluctuating friction torque are neglected. Moreover, considering the power function rule between external load and Coulomb friction, a simplified parametric mechanistic model is developed to describe the changes in joint friction under external load. Second, for the nonlinear residual error of the mechanistic model caused by linear hypothesis and neglecting higher-order terms, a residual compensation model based on eXtreme Gradient Boosting (XGBoost) is proposed. By adopting the boosting ensemble learning strategy, the generalization ability of the residual compensation model is enhanced. The input of the XGBoost model includes the independent variables of the parametric mechanistic model, namely the motor angle, motor velocity, and external load. The output is the difference between actual friction torque and its predicted value by the mechanistic model. Further, the Bayesian optimization method is employed for the optimization of the hyperparameters of the XGBoost model to improve model accuracy and training efficiency. Finally, a series of experiments are performed based on a joint-friction measurement platform and industrial robots to verify the effectiveness of the proposed method. Compared with the parametric mechanistic model, the prediction error of the proposed hybrid model is mainly maintained within ±0.005 N·m, and the peak error, mean absolute error (MAE), and root mean square error (RMSE) are reduced by more than 60%. Comparison experiments with backpropagation neural networks, support vector machines, and long short-term memory neural networks reveal that the nonlinear fluctuation of friction residuals can be well predicted by the proposed method and the MAE and RMSE are reduced by more than 40%. Thus, the proposed XGBoost-based residual compensation model exhibits stronger feature extraction ability and can effectively improve the accuracy of the hybrid friction modeling method.

Introduction The controversial relationship between smoking and prostate cancer (PCa) risk prompted us to conduct a cross-sectional study using the National Health and Nutrition Examination Survey (NHANES) database and apply Mendelian randomization (MR) analyses in order to clarify the possible causal effect of smoking on PCa risk. Methods Using univariate and multivariate logistic regression methods, a secondary analysis of the pooled 2003–2018 NHANES dataset was performed to explore the association between smoking and PCa risk. Propensity-score matching was used to reduce selection bias. Then, we conducted subsequent MR analysis study to investigate the potential causal effect of smoking on PCa risk, with genetic variants of four exposure factors including the lifetime smoking index, light smoking, smoking initiation, and the amount of smoking per day obtained from genomewide association studies, and PCa summary statistics obtained from three database populations. Inverse-variance weighting was the primary analytical method, and weighted median and MR-Egger regression were used for sensitivity analyses. The MR results for the three PCa databases were combined using meta-analysis. Results The study included 16073 NHANES subjects, comprising 554 with PCa and 15519 without PCa. Logistic regression before and after matching did not reveal any significant association. Meta-analysis of the MR results also did not support an association of PCa risk with lifetime smoking index (OR=0.95; 95% CI: 0.83–1.09), light smoking (OR=1.00; 95% CI: 0.95–1.06), smoking initiation (OR=0.99, 95% CI=0.99–1.00), or the amount of smoking per day (OR=1.00; 95% CI: 0.99–1.00) and PCa risk. Conclusions There was no evidence for an association between smoking and the risk of PCa. Further studies are needed to determine if there are any associations of other forms of smoking with the risk of PCa at different stages.

Abstract To evaluate the protective effect of gallic acid on the optic nerve by studying the inhibitory effect of gallic acid on oxidative stress in retinal ganglion cells. 100 male SD rats were randomly divided into four groups: normal control group, simple high IOP group, 0.5% gallic acid experimental group, and 1% gallic acid experimental group. HE staining, immunofluorescence, DHE staining, Western blot, and q-PCR were used to observe the antioxidant effect of gallic acid on the retina of acute ocular hypertension rats. HE staining of the retina of SD rats confirmed that the nucleus of RGCs was clear, the thickness of the RNFL was regular in the normal control group, and the nucleus of RGCs was ruptured and lysed in the simple high intraocular pressure (IOP) group and the gallic acid group, and the thickness of the RNFL was significantly thickened, but the thickness of the RNFL in the gallic acid group was significantly reduced compared with that in the simple high IOP group (p

To prepare bioactive peptides from rapeseed cake directly, the superfine grinding technology was used，and the resulting rapeseed cake superfine powder was used as the material. Single-factor experiments and response surface analysis were used to optimize the preparation extraction. The active peptides were purified by membrane separation and Sephadex G-15 membrane separation, and their antioxidant activity and structure were evaluated. The results showed that the optimal preparation conditions were as follows: grinding time 30 min, solid-to-liquid ratio 1:20(g/mL), pH2.94, enzyme dosage 6300 U/g, temperature 55 ℃, and enzymatic hydrolysis time 2.25 h. Under these conditions, the yield of peptides could reach 83.28%. The F-2 fraction from hydrolysates with molecular mass less than 1000 Da showed good antioxidant activity, with an ABTS+ free radical eliminating rate of 71.62% at a concentration of 1 mg/mL. Furthermore, five peptides were identified, namely PF, SF, TF, IAIPF, and PLDLL which were predicted to have much higher activity. Overall, the results of this study can provide a theoretical basis for the exploration of bioactive peptides directly from rapeseed cakes.

In order to explore the effects of grinding strength on the physicochemical properties and protein extraction of rapeseed meal powder, cryogenic superfine milling was used to prepare six kinds of rapeseed meal powders according to the grinding time (5, 10, 15, 20, 30, 40, and 60 min), namely SGR-5, SGR-10, SGR-15, SGR-20, SGR-30, SGR-40, SGR-60, and conventional crushing one was used as a control, named GR. The results showed that the structure of the rapeseed meal powder was easily destroyed by a moderate superfine grinding compared with the conventional crushing, which was followed by a reduction in their particle size distribution, insoluble dietary fiber content, and water/oil holding capacity, thereby increasing the protein extraction rate. While the grinding process had almost no effect on their total dietary fiber content. Specially, a minimum particle size of the powder would be gotten when grinding for 40 min, about 16 μm (D50), and further grinding would cause the aggregation of powder particles. Moreover, 30 min of superfine grinding was the optimal condition for the extraction of rapeseed meal protein by alkali-extraction. In addition, the alkali pH was another important parameter for the extraction of rapeseed meal protein.

Juvenile open angle glaucoma(JOAG)is a subtype of primary open angle glaucoma(POAG)that severely affects the quality of life of young patients and has a high disability rate. While JOAG is commonly considered an autosomal dominant disease, it has been found to have a diverse mode of inheritance, including autosomal recessive inheritance in specific populations. The variable genetic predisposition of JOAG may be attributed to the co-regulation of several key disease-causing genes, such as MYOC, CYP1B1, and CPAMD8. Mutations in these genes are closely associated with various biological processes in ocular tissues, including cellular metabolic regulation, oxidative stress response, and abnormal induction of programmed death. Therefore, a comprehensive study of the causative genes associated with JOAG is crucial to understanding the specific genetic background of disease onset, progression, and clinical phenotype. This knowledge will provide a strong foundation for early identification and screening of high-risk populations. The objective of this review is to focus on the genetic characterization and genetic studies of JOAG. Through a systematic review of the relevant literature, we summarize the causative genes and their mutations associated with JOAG and explore their potential applications and value in advancing research in the field, aiming to provide valuable insights for the diagnosis and treatment of JOAG.

ObjectiveThe fusion gene is a rare form of α-thalassemia. Patients carrying the fusion gene could be misdiagnosed as normal or -α4.2deletion by the conventional thalassemia detection methods. The aim of this study was to present the detection of fusion genes using routine flow-through hybridization, as well as to analyze hematological and molecular characteristics.MethodsSamples were collected at our hospital from January 2019 to January 2024. Common thalassemia mutations in the Chinese population were conducted by flow-through hybridization. Samples showing faint coloration at the -α4.2 mutation site on hybridization membrane were considered suspicious. Samples detected as suspicious for -α4.2deletion were rechecked by conventional Gap-PCR. Those samples suspected of having -α4.2deletions were finally confirmed with specific primers for Gap-PCR and Sanger sequencing.ResultsOf the 32,083 samples, 25 samples (0.08%) were detected as suspected of having -α4.2 deletion by flow-through hybridization. However, upon reevaluation wtih conventional Gap-PCR reagents capable of detecting -α4.2 deletion, all were found to be negative for the deletion. Specific primers for Gap-PCR were designed, and fusion gene fragments were amplified. DNA sequencing of the HBA gene showed a 7-base mutation corresponding to the α-thalassemia fusion gene. Among the 25 samples, 22 were heterozygous carriers. Three samples were combined: one with Hb QS, one with β-thalassemia, and one with Hb G-Honolulu.Most hematological indices and capillary electrophoresis results were in the normal reference range.ConclusionThe fusion gene was present in 0.08% of the population in the Guangzhou region of Guangdong province, southern China. Conventional genetic methods tend to misdiagnose the fusion gene but can be effectively screened with flow-through hybridization.

Abstract This paper introduces two cases of multiple myeloma, COVID-19 infection during autologous stem cell transplantation, the treatment process, and different results of the two patients, which provides a reference for how to carry out ASCT safely during the COVID-19 normalization stage.

In order to investigate the functional effects of superfine grinding technology on Zanthoxylum bungeanum seed, in this study, superfine grinding technology was used to prepare Zanthoxylum bungeanum superfine powder. The basic components, particle size, color, surface morphology, and the water/oil holding capacity, expansion force, compaction density were investigated and recorded using particle size analyzer, spectrophotometer, and scanning electron microscope (SEM). The results showed that the soluble dietary fiber content of Zanthoxylum bungeanum seed powder gradually increased with the decrease of particle size. In comparison with the conventionally produced powder, the size of superfine powder could decrease to 7.69 μm, along with a larger specific surface area and stronger powder uniformity. As the particle size decreased, the color of the superfine powder gradually increased in L*, a*, and b* values. After superfine grinding, the water-holing capacity, oil-holding capacity, and swelling capacity would increase to 1.65 g/g, 1.16 g/g, and 2.35 mL/g, respectively. In addition, angles of repose and slide increased butthe tap density exhibited the opposite tendency. SEM images revealed that fiber bundle could be more thoroughly crushed with grinding time. In summary, the uniform Zanthoxylum bungeanum seed powder with a smaller particle size, higher powder uniformity, more soluble dietary fiber and better hydration capacity can be prepared through superfine grinding. However, to some extent, superfine grinding will also decrease the density and fluidity of Zanthoxylum bungeanum seed powder.

Understanding the corrosion behavior of Mg alloys in the Cl− environments is crucial to preventing catastrophic accidents in their facilities due to their poor corrosion. The microstructures and corrosion behaviors of the Mg-4Gd-2Nd alloy under different heat-treatment conditions were investigated. The content of Mg41Nd5 in the alloy decreased significantly with increasing heat-treatment temperature. It was found that the formation of solid solution atomic oxides separates the lamellar Mg(OH)2 during the corrosion process of Mg alloys. With the increase of solid solution atomic oxides, lamellar Mg(OH)2 is no longer clustered and laid flat on the alloy surface. The loose Mg(OH)2 corrosion product film is eroded by Cl− and converted to the rod-like Mg2Cl(OH)3·4H2O, which lead to the detachment of the loose lamellar Mg(OH)2 in pieces. Furthermore, the corrosion products of the as-extruded alloy fall off in large blocks, whereas the corrosion products of the heat-treated alloys fall off in small pieces. Therefore, 540 °C-treated specimen exhibits best corrosion resistance.

Adding an anti-corrosion coating to the surface of magnesium (Mg) alloy is an effective means to improve its corrosion resistance, but it is particularly important to enhance the bonding force between the anti-corrosion coating and the Mg matrix. Epoxy resin coating is considered the most cost-effective approach from an industrial standpoint, while the hindering the wider utilization of Mg alloys with epoxy coating in the realm of engineering materials are due to their insufficient adhesion between Mg matrix and the epoxy coating. Here, we demonstrated a simple method for forming an epoxy resin/mineralized film composite coating. The mineralized products coatings were applied to the surface of Mg-3Nd alloy, via a direct reaction between Mg and 15 wt% Na2CO3 solution. Due to the inherent lamellar structure of alkaline magnesium carbonate mineralization film, the mechanical interlocking between the epoxy resin and the Mg substrate are remarkably strengthened. Therefore, this simple surface treatment method is promising to improve the adhesion between the epoxy resin and the matrix. Moreover, the effects of mineralized products coating on the corrosion resistance of Mg with epoxy coating were researched. It was observed that the corrosion resistance of Mg alloy with composite coatings are significantly enhanced. Such an investigation aims to provide a new method for developing a cost-effective and robust epoxy resin/mineralized film composite coating protection structure of Mg alloys in practical applications.

Objective To describe a novel α-thalassemiadeletion identified from a newborn by third-generation sequencing (TGS).Case report The proband, a newborn subject to neonatal capillary electrophoresis (CE) screening, exhibited suspected α0-thalassemia carrier status (Hb Bart’s 3.0%). Notably, both parents had negative results on thalassemia screening during pregnancy. Multiplex ligation-dependent probe amplification (MLPA) presented a deletion between probes 364nt and 472 nt that extended from the HBZ gene to the downstream region of the RGS11 gene. Subsequently, TGS determined the approximated break position of this deletion, indicating a length exceeding 145 kb (chr16:127,815-273,190 del 145376 bp). Sanger sequencing validated the upstream and downstream breakpoints of this deletion. Only maternal data were available for pedigree analysis, with the father's sample lacking. MLPA showed no deletion in the mother, suggesting possible paternal inheritance. The deletion was named Guigang deletion (--Guigang) after the proband’s city of origin, Guigang.Conclusions We reported a novel α-thalassemiadeletion and provided insights into the hematological phenotype and molecular analysis. These findings have implications for genetic counseling and prenatal diagnosis.

Objectives: This study aimed to establish a droplet digital polymerase chain reaction (ddPCR) assay for South-East Asian (SEA) deletion based on a fully integrated digital PCR system DropXpert S6.Methods: A total of 151 whole blood samples, 10 chorionic villus samples, and 17 amniotic fluid samples were collected, including 106 SEA heterozygotes, 43 normal individuals, 10 Hb Bart's hydrops details, and 19 SEA deletions combined with other genotypes.Genotypes of these samples were determined by the Gap-PCR method. We perform a series of optimizations of the ddPCR system to ensure the performance of the entire ddPCR reaction, such as droplet stability, fluorescence clustering, sensitivity, and accuracy.Results: Our assay exhibited 99.4% (177/178) accuracy compared with the Gap-PCR method, and the minimum detection limit of DNA was 0.1 ng/μL.Both targets have reliable linearity, R2 = 0.9999 for the α-thalassemia SEA deletion allele and R2 = 1 for the wild-type allele. The coefficient of variation for α-thalassemia SEA deletion allele detection at 2 and 10 ng/μL concentrations was 5.42% and 1.91%, respectively. In contrast, the coefficient of variation for wild-type allele detection was 4.06% and 1.83%, demonstrating its high quantitative accuracy. In addition, the DropXpert S6 PCR system showed some advantages over other ddPCR instruments, such as reducing testing costs, simplifying and automating the workflow.Conclusions: The DropXpert S6 PCR system provided a highly accurate diagnosis for α-thalassemia SEA deletion and can be used to detect α-thalassemia as an alternative method.

BackgroundPythium insidiosum (P. insidiosum) is the causative agent of pythiosis, an infectious disease with a high morbidity and fatality rate. Pythiosis cases have increased dramatically during the past ten years, particularly in tropical and subtropical areas. Sadly, microbiologists and medical professionals know very little about pythiosis, and the disease is frequently challenging to identify. It is frequently misdiagnosed as a fungal infection.MethodsWe report two cases of pythiosis, one was Pythium keratitis, the other was cutaneous pythiosis. The patient with corneal infection had no underlying disease, while the patient with cutaneous pythiosis had a history of liver cirrhosis, diabetes, and psoriasis. The corneal sample and subcutaneous pus were sent for metagenomic Next-Generation Sequencing (mNGS). To further diagnose the isolated strain, P. insidiosum zoospores were induced to produce by co-incubation with sterile grass leaves in sterile pond water. Their zoospores were used as an inoculum for drug susceptibility testing by disk diffusion and broth microdilution method.ResultsThe mNGS of two cases were reported as P. insidiosum. Zoospores were produced after incubation 48h. The zoospores were collected for drug susceptibility assay. All antifungal drugs, antibacterial drugs of β-Lactams, vancomycin, levofloxacin, ciprofloxacin, gentamicin, trimethoprim-sulfamethoxazole, clindamycin have no inhibitory activity against P. insidiosum in vitro. Minocycline, tigecycline, linezolid, erythromycin and azithromycin have significant in vitro activity against P. insidiosum. Based on the susceptibility results, the drug was changed from itraconazole to linezolid and minocycline, along with multiple debridements and drainage for cutaneous pythiosis. The patient was discharged after 24 days of treatment.ConclusionsEarly and accurate identification, combined with aggressive surgical debridement and appropriate drug therapy, can greatly improve patient managements. Conventional culture and zoospore induction remain gold standard for diagnosis; however, DNA-based method should be performed simultaneously. The drug susceptibility testing provides profound effects on proper drug selection against P. insidiosum.

Objective This study was performed to evaluate the efficacy of robot-assisted thoracoscopic surgery (RATS) in the treatment of pulmonary sequestration (PS) in children.Methods All video-assisted thoracoscopic surgery (VATS) and RAST performed on patients with PS at a single center from May 2019 to July 2023 were identified. The χ2 and Wilcoxon tests were used to compare the perioperative outcomes between VATS and RATS groups.Results Ninety-three patients underwent RATS while 77 patients underwent VATS. In both two groups, one patient converted to thoracotomy and no surgical mortality case. The median operation time was longer for the RATS group compared with the VATS group (75 min vs. 60 min, p

High temperature induces heat stress, adversely affecting the growth and lactation performance of cows. Research has shown the protective effect of taurine against hepatotoxicity both in vivo and in vitro. This study aimed to investigate the effect of taurine on the metabolomics of mammary epithelial cells of dairy cows under high-temperature conditions. Mammary epithelial cells were exposed to 0 mmol/L (HS, control), 8 mmol/L (HT-8), and 32 mmol/L (HT-32) of taurine, then incubated at 42°C for 6 h. Metabolomics analysis was conducted using Liquid Chromatograph Mass Spectrometer (LC–MS). Compared with the HS group, 2,873 and 3,243 metabolites were detected in the HT-8 group in positive and negative ion modes. Among these, 108 and 97 metabolites were significantly upregulated in positive and negative ion modes, while 60 and 166 metabolites were downregulated. Notably, 15 different metabolites such as palmitic acid, adenine and hypoxanthine were screened out in the HT-8 group. Compared with the HS group, 2,873 and 3,243 metabolites were, respectively, detected in the HT-32 group in the positive and negative ion modes. Among those metabolites, 206 metabolites were significantly up-regulated, while 206 metabolites were significantly downregulated in the positive mode. On the other hand, 497 metabolites were significantly upregulated in the negative mode, while 517 metabolites were reported to be downregulated. Noteworthy, 30 distinct metabolites, such as palmitic acid, phytosphingosine, hypoxanthine, nonanoic acid, and octanoic acid, were screened out in the HT-32 group. KEGG enrichment analysis showed that these metabolites were mainly involved in lipid metabolism, purine metabolism and other biological processes. Overall, our study indicates that taurine supplementation alters the metabolites primarily associated with purine metabolism, lipid metabolism and other pathways to alleviate heat stress in bovine mammary epithelial cells.

Abstract Background Cross-species transmission of zoonotic IAVs to humans is potentially widespread and lethal, posing a great threat to human health, and their cross-species transmission mechanism has attracted much attention. miRNAs have been shown to be involved in the regulation of IAVs infection and immunity, however, few studies have focused on the molecular mechanisms underlying miRNAs and mRNAs expression after IAVs cross-species infection. Methods We used tree shrews, a close relative of primates, as a model and used RNA-Seq and bioinformatics tools to analyze the expression profiles of DEMs and DEGs in the nasal turbinate tissue at different time points after the newly emerged swine influenza A virus SW2783 cross-species infection with tree shrews, and miRNA-mRNA interaction maps were constructed and verified by RT-qPCR, miRNA transfection and luciferase reporter assay. Results 14 DEMs were screened based on functional analysis and interaction map, miR-760-3p, miR-449b-2, miR-30e-3p, and miR-429 were involved in the signal transduction process of replication and proliferation after infection, miR-324-3p, miR-1301-1, miR-103-1, miR-134-5p, miR-29a, miR-31, miR-16b, miR-34a, and miR-125b participate in negative feedback regulation of genes related to the immune function of the body to activate the antiviral immune response, and miR-106b-3p may be related to the cross-species infection potential of SW2783, and the expression level of these miRNAs varies in different days after infection. Conclusions The miRNA regulatory networks were constructed and 14 DEMs were identified, some of them can affect the replication and proliferation of viruses by regulating signal transduction, while others can play an antiviral role by regulating the immune response. It indicates that abnormal expression of miRNAs plays a crucial role in the regulation of cross-species IAVs infection, which lays a solid foundation for further exploration of the molecular regulatory mechanism of miRNAs in IAVs cross-species infection and anti-influenza virus targets.

A large spontaneous mass on the dorsal abdomen near the hip joint was found in an aged female Tupaia belangeri subsp. yaoshanensis after 5 years of routine feeding. The tumor in the diseased tree shrew was huge, with an intact surface and no ulceration; however, it caused inconvenience in movement while maintaining a good mental state. After inhalation anesthesia with isoflurane (2%-4%), the tree shrew was euthanized after the tree shrew entered deep anesthesia. Anatomical dissection of the tumor, the tumor boundary was unclear and infiltrated into surrounding tissues. HE staining showed that small focal pleomorphism and large areas of adipocytes were seen in the tumor tissue. The pleomorphic sarcoma area was mainly composed of atypical epithelioid cells with easily visible nuclear divisions. The size of the adipocytes was significantly different, and more pleomorphic adipocytes were seen. The cell volume was large, the nucleus was deeply stained and deformed, the edge was impressed, and the cytoplasm was seen with multiple vesicular lipid droplets. Immunohistochemical results showed that the tumor cells were positive for Vimentin, the small focal polymorphic adipocyte nucleus was positive for S-100, and Ki-67 exhibited a higher proportion of positivity. Combined with HE staining and immunohistochemical results, the spontaneous tumor in this tree shrew was comprehensively diagnosed as pleomorphic liposarcoma.

Abstract Background Hematoma expansion is a determinant of poor outcome of intracerebral hemorrhage but occurs frequently, especially in warfarin-associated intracerebral hemorrhage (W-ICH). In the present study, we employ the warfarin-associated intracerebral hemorrhage (W-ICH) rat model, to explore the efficacy and potential mechanism of glibenclamide pretreatment on hematoma expansion after intracerebral hemorrhage, hoping to provide proof of concept that glibenclamide in stroke primary and secondary prevention is also potentially beneficial for intracerebral hemorrhage patients at early stage. Methods In the present study, we tested whether glibenclamide, a common hypoglycemic drug, could attenuate hematoma expansion in a rat model of W-ICH. Hematoma expansion was evaluated using magnetic resonance imaging; brain injury was evaluated by brain edema and neuronal death; and functional outcome was evaluated by neurological scores. Then blood–brain barrier integrity was assessed using Evans blue extravasation and tight junction-related protein. Results The data indicated that glibenclamide pretreatment significantly attenuated hematoma expansion at 24 h after W-ICH, thus mitigating brain edema and neuronal death and promoting neurological function recovery, which may benefit from alleviating blood–brain barrier disruption by suppressing matrix metallopeptidase-9. Conclusions The results indicate that glibenclamide pretreatment in stroke primary and secondary prevention might be a promising therapy for hematoma expansion at the early stage of W-ICH.

In this work, a synergistic strategy of small cation substitution and charge compensation to realize efficient red luminescence has been developed, which greatly improves the luminescence performance of Mg2InSbO6:Mn4+ by modulating the degree of distortion of the Mn4+ lattice site. The doping Mn ion is stabilized in the tetravalent state and occupies the Sb5+ site. After the Sc3+-In3+ substitution, the emission characteristic of the original Mg2InSbO6:Mn4+ is regulated and effectively red-shifted, and the extruded [MnO6] octahedron present distorted due to the aberration of the near-neighboring lattice sites of Mn4+. Through the Sc3+-In3+ substitution and Li+ compensation, the optimal thermal stability at 423 K is enhanced by 19.1% compared with that of Mg2InSbO6:Mn4+. Surprisingly, the designed Mg2In0.3Sc0.7SbO6:0.003Mn4+,Li+ phosphor exhibits excellent quantum yield (82.02%) and high color purity (97.3%), which is higher than most of the reported Mn4+-doped phosphors. Moreover, the growth of sweet potatoes by combining the plant growth illumination device encapsulated by the phosphor is implemented. The relevant growth parameters further confirm that the designed phosphors have a great potential application in the field of plant growth lighting.

Summary: The vaginal microbiome’s composition varies among ethnicities. However, the evolutionary landscape of the vaginal microbiome in the multi-ethnic context remains understudied. We perform a systematic evolutionary analysis of 351 vaginal microbiome samples from 35 multi-ethnic pregnant women, in addition to two validation cohorts, totaling 462 samples from 90 women. Microbiome alpha diversity and community state dynamics show strong ethnic signatures. Lactobacillaceae have a higher ratio of non-synonymous to synonymous polymorphism and lower nucleotide diversity than non-Lactobacillaceae in all ethnicities, with a large repertoire of positively selected genes, including the mucin-binding and cell wall anchor genes. These evolutionary dynamics are driven by the long-term evolutionary process unique to the human vaginal niche. Finally, we propose an evolutionary model reflecting the environmental niches of microbes. Our study reveals the extensive ethnic signatures in vaginal microbial ecology and evolution, highlighting the importance of studying the host-microbiome ecosystem from an evolutionary perspective.

Abstract Controlling the selectivity of the electrocatalytic reduction of carbon dioxide into value-added chemicals continues to be a major challenge. Bulk and surface lattice strain in nanostructured electrocatalysts affect catalytic activity and selectivity. Here, we unravel the complex dynamics of synergistic lattice strain and stability effects of Cu-Ag tandem catalysts through a previously unexplored combination of in situ nanofocused X-ray absorption spectroscopy and Bragg coherent diffraction imaging. Three-dimensional strain maps reveal the lattice dynamics inside individual nanoparticles as a function of applied potential and product yields. Dynamic relations between strain, redox state, catalytic activity and selectivity are derived. Moderate Ag contents effectively reduce the competing evolution of H2 and, concomitantly, lead to an enhanced corrosion stability. Findings from this study evidence the power of advanced nanofocused spectroscopy techniques to provide new insights into the chemistry and structure of nanostructured catalysts.

Abstract Background Atelocollagen (AC) is a low-immunogenic collagen derivative with longer degradation time, which can be a suitable material for alveolar ridge preservation (ARP). However, there are few human studies on AC using for ARP. This research aims to radiographically evaluate the efficacy of AC in comparison to deproteinized bovine bone minerals covered with a collagen membrane (DBBM/CM) in ARP. Methods Medical records in the Implantology Department of the Hospital of Stomatology of Wuhan University were screened for patients who received flapless ARP using either AC or DBBM/CM. A total of 58 patients were included in this retrospective study. 28 patients were treated with AC, while 30 patients were used DBBM/CM. Cone-beam computed tomography (CBCT) scans were taken before extraction and after 6 months of healing. To assess the dimensional change of the extraction sockets, the scanning data were output and transferred to the digital software to measure horizontal bone width change, vertical bone height change and bone volume change in region of interest. To evaluate the bone quality of healed sockets, the bone density of virtual implants was evaluated. Results The horizontal bone width changes at all five different levels showed no significant difference between the two groups. The largest horizontal bone width decrement in both groups occurred at the crest of ridge, which decreased 3.71 ± 1.67 mm in AC group and 3.53 ± 1.51 mm in DBBM/CM group (p = 0.68). At the central buccal aspect, the ridge height reduced 0.10 ± 1.30 mm in AC group, while increased 0.77 ± 2.43 mm in DBBM/CM group (p = 0.10). The vertical bone height differences between two groups showed no statistical significance. The percentages of volume absorption in AC group and DBBM/CM group were 12.37%±6.09% and 14.54%±11.21%, respectively. No significant difference in volume absorption was found (p = 0.36). The average bone density around virtual implants in AC group (649.41 ± 184.71 HU) was significantly lower than that in DBBM/CM group (985.23 ± 207.85 HU) (p

Battery energy storage system (BESS) has been regarded as an effective technology to regulate system frequency for power systems. However, the cost and the system security of battery energy storage are the bottle necks for the battery energy storage system to be applied to practical projects for frequency regulation. Comparing with the large-scale battery energy storage system, the small-scale energy storage system has better robustness and could reduce the cost and improve the system security with lower energy capacity and wider regional distribution. However, coordinating the state of charge (SOC) of a large number of small-scale battery storage system to provide effective frequency regulation service is a challenge for the operation of power systems. In this paper, a hierarchical energy management strategy, which can be applied to different scenarios with and without limited communication systems, has been proposed to coordinate a large number of small-scale energy storage systems to regulate frequency for power systems. The rated power capacity, energy capacity, and SOC of the BESS are considered in the proposed strategy to maximize the capability of frequency regulation for power systems. The proposed strategy can be applied to power systems without powerful and expensive communication systems and coordinate BESS according to SOC of the BESS and the quality of communication system. The resilience of power systems after extreme natural events can be enhanced by the frequency regulation service of BESS under proposed strategy.

Vibration problems have become one of the most important factors affecting robot performance. To this end, a terminal residual vibration suppression method based on joint trajectory optimization is proposed to improve the accuracy and stability of robot motion. Firstly, based on the characteristics of the friction nonlinearity due to joint coupling and physical feasibility of dynamic parameters, a semidefinite programming method is used to identify dynamic parameters with actual physical meaning, thereby obtaining an accurate dynamic model. Then, based on the result of the residual vibration time domain analysis, a joint trajectory optimization model with the goal of minimizing joint tracking error is established. The Chebyshev collocation method is used to discretize the optimization model. The dynamic model is used as the optimization constraint, and barycentric interpolation is used to obtain the optimized joint motion trajectory. Finally, industrial robot experiments prove that the vibration suppression method proposed in this article can reduce the maximum acceleration amplitude of residual vibration by 62% and the vibration duration by 71%. Compared with the input shaping method, the method proposed in this paper can reduce the terminal residual vibration more effectively and ensure the consistency of running time and trajectory.

Objective To observe the primary tumor of tree shrews and to provide a basis for studying the pathogenesis and prevention of trichoepithelioma.Methods A tumor was discovered in the chest and abdomen of a tree shrew during natural cultivation. The tree shrew was anesthetized, and the tumor was surgically removed. Hematoxylin and eosin (HE) staining and immunohistochemical staining were performed on the tumor tissue after paraffin section, and the tumor cells were isolated and cultured by passage. The isolated tumor cells were subcutaneously injected into healthy tree shrews and nude mice. The tumorigenesis of tumor cells in vivo was observed once a day, with nude mice continuously observed for 2 months and tree shrews observed for more than 6 months.Results HE staining showed that the basal cells in the dermis were arranged as a whole, like a string of petals, forming nests and stripe-like structures with clear boundaries. The observation results after magnification revealed that the tumor cells were arranged in a pallisade-like and basal pattern, with deep nuclear staining and minimal cytoplasmic. Immunohistochemical staining showed the high expression of CK protein and low proportion expression of ki-67 protein in tumor cells, as well as the high expression of vimentin and low expressions of Bcl2 and CD10 in tumor cell mesenchyme. The isolated tumor cells grew well in DMEM medium containing 10% fetal bovine serum and could be cultured by passage, but no tumor formation was observed in healthy tree shrews and nude mice inoculated with tumor cells.Conclusion Combined with the location of the tumor, overall morphology, HE staining, and immunohistochemical results, the thoracoabdominal mass of the tree shrew was diagnosed as a trichoepithelioma.

Abstract Background and Aim The biological functions and clinical implications of lysophosphatidylcholine acyltransferase 1 (LPCAT1) remain unclarified in gastric cancer (GC). The aim of the current study was to explore the possible clinicopathological significance of LPCAT1 and its perspective mechanism in GC tissues. Materials and Methods The protein expression and mRNA levels of LPCAT1 were detected from in‐house immunohistochemistry and public high‐throughput RNA arrays and RNA sequencing. To have a comprehensive understanding of the clinical value of LPCAT1 in GC, all enrolled data were integrated to calculate the expression difference and standard mean difference (SMD). The biological mechanism of LPCAT1 in GC was confirmed by computational biology and in vitro experiments. Migration and invasion assays were also conducted to confirm the effect of LPCAT1 in GC. Results Both protein and mRNA expression levels of LPCAT1 in GC were remarkably higher than those in noncancerous controls. Comprehensively, the SMD of LPCAT1 mRNA was 1.11 (95% CI = 0.86–1.36) in GC, and the summarized AUC was 0.85 based on 15 datasets containing 1727 cases of GC and 940 cases of non‐GC controls. Moreover, LPCAT1 could accelerate the invasion and migration of GC by boosting the neutrophil degranulation pathway and disturbing the immune microenvironment. Conclusion An increased level of LPCAT1 may promote the progression of GC.

During vascular development, endothelial cells (ECs) undergo arterialization in response to genetic programs and shear stress-triggered mechanotransduction, forming a stable vasculature. Although the Notch receptor is known to sense shear stress and promote EC arterialization, its downstream mechanisms remain unclear. In this study, the Notch downstream miR-342-5p was found to respond to shear stress and promote EC arterialization. Shear stress upregulated miR-342-5p in a Notch-dependent manner in human umbilical vein endothelial cells (HUVECs). miR-342-5p overexpression upregulated the shear stress-associated transcriptomic signature. Moreover, miR-342-5p upregulated arterial markers and promoted EC arterialization in a Matrigel plug assay and retinal angiogenesis model. In contrast, miR-342-5p knockdown downregulated arterial markers, compromised retinal arterialization, and partially abrogated shear stress and Notch activation-induced arterial marker upregulation. Mechanistically, miR-342-5p overexpression suppressed MYC to repress EC proliferation and promote arterialization, achieved by promoting MYC protein degradation by targeting the EYA3. Consistently, EYA3 overexpression rescued miR-342-5p-mediated MYC downregulation and EC arterialization. In vivo, miR-342-5p expression was notably decreased in the ligated artery in a hindlimb ischemia model, and an intramuscular injection of miR-342-5p promoted EC arterialization and improved perfusion. In summary, miR-342-5p, a mechano-miR, mediates the effects of shear stress-activated Notch on EC arterialization and is a potential therapeutic target for ischemic diseases.

Background: Prenatal diagnosis and genetic counseling play an important role in preventing and controlling birth defects. No reports were found of prenatal diagnosis of couples carrying both the thalassemia and deafness genes. In this study, we presented the prenatal screening and diagnosis of a couple with both thalassemia and deafness genes, contributing to better genetic counseling.Case Report: A couple visited our hospital for a routine prenatal examination. As required by the policy in our region, they underwent screening and genetic diagnosis for thalassemia. Meanwhile, they did not accept the recommendation to test for spinal muscular atrophy and deafness genes. The female was confirmed to be a Hb Quong Sze (Hb QS) carrier (αQSα/αα, βN/βN), and the male had Hb H disease combined with β-thalassemia (--SEA/αCSα, βCDs41-42 (-TTCT)/βN). A prenatal diagnosis of the fetus revealed a Hb CS heterozygote. Subsequent complementary testing showed that the male was a double heterozygote of the GJB2 gene c.299_300delAT combined with c.109G>A, and Sanger sequencing confirmed that the female was a carrier of c.508_511dup in the GJB2. Fortunately, the chorionic villi results indicated that the fetus was only a carrier of deafness.Conclusion: Since both partners carried thalassemia and deafness genes, the couple required prenatal diagnosis for the respective mutations. Expanded carrier screening (ECS) is a more advanced technology that can detect multiple disease genes simultaneously.

CAR-T cell therapy, a novel therapeutic approach that has attracted much attention in the field of cancer treatment at present, has become the subject of many studies and has shown great potential in the treatment of hematological malignancies, such as leukemia and lymphoma. This study aims to analyze the characteristics of articles published on CAR-T cell therapy in the lymphoma field and explore the existing hotspots and frontiers. The relevant articles published from 2013 to 2022 were retrieved from the Web of Science Core Collection. CiteSpace, VOSviewer, Bibliometric online analysis platform, Microsoft Excel, and R software were used for bibliometric analysis and visualization. The number of publications related to the research has been increasing year by year, including 1023 articles and 760 reviews from 62 countries and regions, 2092 institutions, 1040 journals, and 8727 authors. The United States, China, and Germany are the main publishing countries in this research field. The top 10 institutions are all from the United States, the journal with the highest impact factor is BLOOD, the author with the most publications is Frederick L Locke, and the most influential author is Carl H June. The top three keywords are “Lymphoma,” “Immunotherapy,” and “Therapy.” “Maude (2014)” is the most cited and strongest burstiness reference over the past decade. This study provides a comprehensive bibliometric analysis of CAR-T cell therapy in lymphoma, which can help researchers understand the current research hotspots in this field, explore potential research directions, and identify future development trends.

ABSTRACTObjective The 4.2 kb deletion (-α4.2/) is a common a+-thalassemia with a carrier rate, followed by the South-East Asian deletion (–SEA) and the 3.7 kb deletion (-α3.7/). There are few reports about 4.2 kb deletion sub-types. Herein, we present a patient with double heterozygous -α4.2Ⅰ/-α4.2Ⅱwho was identified using third-generation sequencing (TGS).Methods Hematology and hemoglobin fraction analysis were carried out by complete blood count (CBC) and capillary electrophoresis (CE). Gap-PCR was used to detect the common deletional α-thalassemia, and multiple ligation-dependent probe amplification (MLPA) was performed to screen the large deletion. Sanger sequencing identified the variant. The different deletions were confirmed by TGS.Results CBC showed the patient with microcytic hypochromic anemia, and CE indicated the presence of a Hb variant. Gap-PCR and MLPA detected 4.2 kb deletion homozygotes (-α4.2/-α4.2). The Hb variant was confirmed as Hb Q-Thailand by Sanger sequencing. The patient was identified as compound heterozygous of 4.2 kb deletion and Hb Q-Thailand (-α4.2/-α4.2-Q-Thailand, -α4.2Ⅰ/-α4.2Ⅱ) using TGS.Conclusions Hb Q-Thailand (-α4.2-Q-Thailand/) complex 4.2 kb deletion heterozygote (-α4.2/) is easily misdiagnosed as 4.2 kb homozygous using Gap-PCR and MLPA. The TGS enables the identification of the two different 4.2 kb deletion sub-types.

ABSTRACTObjectives To report the hematological and molecular characteristics of a novel α-globin variant found among Chinese families.Methods This study was done on two unrelated families (F1 and F2). Hematological results were obtained by an automated blood cell analyzer. Hemoglobin (Hb) fraction analysis was carried out using capillary electrophoresis (CE) and high-performance liquid chromatography (HPLC). Gap-PCR and reverse dot blot (RDB) methods were used to detect the common α-thalassemia mutations in the Chinese population. The Hb variants were defined by Sanger sequencing.Results Hb fraction analysis of F2 cord blood using HPLC showed an abnormal peak (3.5%) of the S-window, but CE presented a 12.2% abnormal peak at zone 5(S). Similar results of CE were observed from the F1 twin's cord blood. Compared with newborns, Hb analysis of F2 father using HPLC demonstrated an abnormal peak (16.9%) of S-window and an unknown peak (0.5%) at a retention time of 4.60 min, respectively. In contrast, CE revealed a high Hb F peak at zone 7 and an unknown peak at zone 1. There was no abnormality detected with Gap-PCR and RDB in these patients. However, Sanger sequencing confirmed the presence of a new heterozygous mutation (GAC>GGC) at codon 74 of the HBA2 gene (HBA2:c.224A>G), resulting in a novel Hb variant. We named it Hb Liangqing for the birthplace of the proband.Conclusion This is the first report of Hb Liangqing detected by HPLC and CE. The normal hematological phenotype suggests that it may be a benign Hb variant.

Abstract Background Congenital pulmonary airway malformation (CPAM) is the most frequent pulmonary developmental malformation and the pathophysiology remains poorly understood. This study aimed to identify the characteristic gene expression patterns and the marker genes essential to CPAM. Methods Tissues from the cystic area displaying CPAM and the area of normal appearance were obtained during surgery. Bulk RNA sequencing (RNA-seq) and single-cell RNA sequencing (scRNA-seq) were performed for integrating analysis. Iterative weighted gene correlation network analysis (iWGCNA) was used to identify specifically expressed genes to CPAM. Results In total, 2074 genes were significantly differentially expressed between the CPAM and control areas. Of these differentially expressed genes (DEGs), 1675 genes were up-regulated and 399 genes were down-regulated. Gene ontology analysis revealed these DEGs were specifically enriched in ciliated epithelium and involved in immune response. We also identified several CPAM-related modules by iWGCNA, among them, P15_I4_M3 module was the most influential module for distinguishing CPAMs from controls. By combining the analysis of the expression dataset from RNA-seq and scRNA-seq, SPOCK2, STX11, and ZNF331 were highlighted in CPAM. Conclusions Through our analysis of expression datasets from both scRNA-seq and bulk RNA-seq of tissues obtained from patients with CPAM, we identified the characteristic gene expression patterns associated with the condition. Our findings suggest that SPOCK2 could be a potential biomarker gene for the diagnosis and therapeutic target in the development of CPAM, whereas STX11 and ZNF331 might serve as prognostic markers for this condition. Further investigations with larger samples and function studies are necessary to confirm the involvement of these genes in CPAM.

Inter-domain routing systems are important complex networks on the Internet. It has been paralyzed several times in recent years. The researchers pay close attention to the damage strategy of inter-domain routing systems and think it is related to the attacker's behavior. The key to the damage strategy is knowing how to select the optimal attack node group. In the process of selecting nodes, the existing research seldom considers the attack cost, and there are some problems, such as an unreasonable definition of attack cost and an unclear optimization effect. To solve the above problems, we designed an algorithm to generate damage strategies for inter-domain routing systems based on multi-objective optimization (PMT). We transformed the damage strategy problem into a double-objective optimization problem and defined the attack cost related to the degree of nonlinearity. In PMT, we proposed an initialization strategy based on a network partition and a node replacement strategy based on partition search. Compared with the existing five algorithms, the experimental results proved the effectiveness and accuracy of PMT.

As a high-quality peptide source with rich sources, natural environmental protection and none side effects，high Fischer ratio oligopeptides widely exist in natural animals and plants.High Fischer ratio oligopeptides have a variety of biological activities, such as anti-fatigue, anti-oxidation, sobering up, adjuvant treatment of liver disease and phenylketonuria. Because of its high content of branched chain amino acids, high Fischer ratio oligopeptides can improve the imbalance between branched chain amino acids and aromatic amino acids in patients with liver disease, and play an important role in the adjuvant treatment of chronic liver disease and its complications. This paper mainly reviews the raw materials, preparation, separation and purification methods, liver protection efficacy and action mechanism of food-derived high Fischer ratio oligopeptides, focusing on the introduction of several raw material proteins including plant protein, aquatic product protein and milk derived protein in animal protein, two preparation methods including enzymatic hydrolysis and microbial fermentation, several separation and purification methods including membrane separation, activated carbon adsorption and chromatographic separation, and the liver protection effect of high Fischer ratio oligopeptides and three ways to play the role of liver protection. This review is trying to provide a theoretical reference for the future development and application of food-derived high Fischer ratio oligopeptides in the field of food and medicine.

Brain hemorrhage: Causes of fluid build-up on the brain Inhibiting a key inflammatory protein and thereby protecting the blood-brain barrier following brain hemorrhage may prevent the build-up of fluid on the brain (hydrocephalus). Using rat models and cell cultures, Yujie Chen and Hua Feng at the Third Military Medical University in Chongqing, China, and co-workers examined how posthemorrhagic hydrocephalus occurs. They found that the acute inflammatory response activated immediately after a brain hemorrhage, which is driven by a critical protein complex involved in innate immunity called the NLRP3 inflammasome, triggers the formation of lipid droplets in the choroid plexus, a part of the brain adjacent to the blood-brain barrier. The lipid droplets interact with mitochondria, increasing the release of reactive oxygen species and damaging the blood-brain barrier. This barrier dysfunction triggers hydrocephalus. Blocking NLRP3 activity improved the function of the barrier following hemorrhage.

Abstract Background Activated immune cells (IC) in the tumor microenvironment (TME) are critical for anti-tumor efficacy. Greater understanding of the dynamic diversity and crosstalk between IC is needed to clarify their association with immune checkpoint inhibitor efficacy. Methods Patients from three tislelizumab monotherapy trials in solid tumors (NCT02407990, NCT04068519, NCT04004221) were retrospectively divided into subgroups by CD8+ T-cell and macrophage (Mφ) levels, assessed via multiplex immunohistochemistry (mIHC; n = 67) or gene expression profiling (GEP; n = 629). Results A trend of longer survival was observed in patients with both high CD8+ T-cell and Mφ levels versus other subgroups in the mIHC analysis (P = 0.11), which was confirmed with greater statistical significance in the GEP analysis (P = 0.0001). Co-existence of CD8+ T cells and Mφ was coupled with elevated CD8+ T-cell cytotoxicity, T-cell trafficking, MHC class I antigen presentation signatures/genes, and enrichment of the pro-inflammatory Mφ polarization pathway. Additionally, a high level of pro-inflammatory CD64+ Mφ density was associated with an immune-activated TME and survival benefit with tislelizumab (15.2 vs. 5.9 months for low density; P = 0.042). Spatial proximity analysis revealed that closer proximity between CD8+ T cells and CD64+ Mφ was associated with a survival benefit with tislelizumab (15.2 vs. 5.3 months for low proximity; P = 0.024). Conclusions These findings support the potential role of crosstalk between pro-inflammatory Mφ and cytotoxic T cells in the clinical benefit of tislelizumab. Trial registration NCT02407990, NCT04068519, NCT04004221.

Autonomous driving, as a pivotal technology in modern transportation, is progressively transforming the modalities of human mobility. In this domain, vehicle detection is a significant research direction that involves the intersection of multiple disciplines, including sensor technology and computer vision. In recent years, many excellent vehicle detection methods have been reported, but few studies have focused on summarizing and analyzing these algorithms. This work provides a comprehensive review of existing vehicle detection algorithms and discusses their practical applications in the field of autonomous driving. First, we provide a brief description of the tasks, evaluation metrics, and datasets for vehicle detection. Second, more than 200 classical and latest vehicle detection algorithms are summarized in detail, including those based on machine vision, LiDAR, millimeter-wave radar, and sensor fusion. Finally, this article discusses the strengths and limitations of different algorithms and sensors, and proposes future trends.

This paper analyzes traditional vibration suppression methods in order to solve the vibration problem caused by the stiffness of flexible industrial robots. The principle of closed-loop control dynamic feedforward vibration suppression is described as the main method for solving robot vibration suppression. This paper proposes a method for time-lag filtering based on T-trajectory interpolation, which combines the T-planning curve and the time-lag filtering method. The method’s basic principle is to dynamically adjust the trajectory output through the algorithm, which effectively suppresses the amplitude of the harmonic components of a specific frequency band to improve the vibration response of industrial robot systems. This experiment compared traditional vibration suppression methods with the time-lag filtering method based on T-trajectory interpolation. A straight-line method was proposed to measure the degree of vibration. The results demonstrate that the time-lag filtering method based on T-trajectory interpolation is highly effective in reducing the vibration of industrial robots. This makes it an excellent option for scenarios that demand real-time response and high-precision control, ultimately enhancing the efficiency and stability of robots in performing their tasks.

Human cancers induce a chaotic, dysfunctional vasculature that promotes tumor growth and blunts most current therapies; however, the mechanisms underlying the induction of a dysfunctional vasculature have been unclear. Here, we show that split end (SPEN), a transcription repressor, coordinates rRNA synthesis in endothelial cells (ECs) and is required for physiological and tumor angiogenesis. SPEN deficiency attenuated EC proliferation and blunted retinal angiogenesis, which was attributed to p53 activation. Furthermore, SPEN knockdown activated p53 by upregulating noncoding promoter RNA (pRNA), which represses rRNA transcription and triggers p53-mediated nucleolar stress. In human cancer biopsies, a low endothelial SPEN level correlated with extended overall survival. In mice, endothelial SPEN deficiency compromised rRNA expression and repressed tumor growth and metastasis by normalizing tumor vessels, and this was abrogated by p53 haploinsufficiency. rRNA gene transcription is driven by RNA polymerase I (RNPI). We found that CX-5461, an RNPI inhibitor, recapitulated the effect of Spen ablation on tumor vessel normalization and combining CX-5461 with cisplatin substantially improved the efficacy of treating tumors in mice. Together, these results demonstrate that SPEN is required for angiogenesis by repressing pRNA to enable rRNA gene transcription and ribosomal biogenesis and that RNPI represents a target for tumor vessel normalization therapy of cancer.

Net ecosystem productivity (NEP) is a critical indicator of the CO2 capture capacity of vegetation ecosystems. Based on the land classification and clumping index (CI) datasets, the key parameters of the Carnegie–Ames–Stanford Approach (CASA) model, including fraction of photosynthetic active radiation (FPAR) and maximum light use efficiency $({{\rm{\varepsilon }}}_{\text{max}})$, were optimized. Then, the NEP of China's terrestrial ecosystems was estimated, using the improved CASA coupled with a soil respiration model. Finally, the accuracy of NEP estimation was evaluated by observation data from ChinaFLUX station. The research results indicated the RMSE of the improved NEP estimations decreased from 21.139 to 10.179 (unit: $\text{gC} \cdot \text{m}^{- \text{2}} \cdot \text{month}^{ - \text{1}}$), and the R2 value increased from 0.413 to 0.832, indicating that optimizing the parameters ${{\rm{\varepsilon }}}_{\text{max}}$ and FPAR are both effective methods to improve the model. The spatiotemporal variation of China's NEP was analyzed using the optimized results. The NEP value of China shows a decreasing distribution pattern from southeast to northwest, and the values of different regions are in the order South > North > Qinghai–Tibet > Northwest. The monthly NEP variation in different regions of China is a unimodal curve, reaching the maximum in summer. This study optimized the NEP estimation, which can better characterize the distribution pattern of carbon sinks/sources in China's terrestrial ecosystems and lay a scientific foundation for developing regional carbon neutrality schemes.

The realization of intelligent mining is the only method for realizing high-quality development in the coal industry. As the forefront working link in mine production, achieving automatic roadway tunneling control is key to improving production efficiency, enhancing intelligence, and reducing accident rates at fully mechanized tunneling working faces. Among various detection techniques, machine vision technology stands out with advantages of non-contact measurement, rich information acquisition, and high detection accuracy. The detection and control of tunneling equipment groups based on machine vision has become a research hotspot in the intelligence process of coal mines. This study first introduces the key technologies of a visual detection system, including camera calibration, image preprocessing, feature extraction, visual matching, target segmentation and recognition, visual measurement, and 3D reconstruction. It then elaborates on detection principles, workflows, limitations, precautions, and development status of various vision detection systems in practical application scenarios at tunneling faces, such as tunneling equipments, anchoring systems, transportation systems, and safety auxiliary systems, which significantly improve production safety and efficiency. Finally, considering challenging work conditions and strong interference in mines, the successful adaptation of machine vision to excavation sites relies on addressing technical challenges related to poor environment adaptability, limited imaging field of view, and low intelligence level. Furthermore, according to existing research results and the current technical status, this paper forecasts key technologies that need to be developed in the future for coal mine intelligent equipment systems based on machine vision, including multi-sensor information fusion, equipment group collaborative control, and digital twin-driven remote monitoring.