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In the pathogenesis of osteoarthritis, various signaling pathways may influence the bone joint through a common terminal pathway, thereby contributing to the pathological remodeling of the joint. Semaphorins (SEMAs) are cell-surface proteins actively involved in and primarily responsible for regulating chondrocyte function in the pathophysiological process of osteoarthritis (OA). The significance of the SEMA family in OA is increasingly acknowledged as pivotal. This review aims to summarize the mechanisms through which different members of the SEMA family impact various structures within joints. The findings indicate that SEMA3A and SEMA4D are particularly relevant to OA, as they participate in cartilage injury, subchondral bone remodeling, or synovitis. Additionally, other elements such as SEMA4A and SEMA5A may also contribute to the onset and progression of OA by affecting different components of the bone and joint. The mentioned mechanisms demonstrate the indispensable role of SEMA family members in OA, although the detailed mechanisms still require further exploration. [ABSTRACT FROM AUTHOR]

Structural variations (SVs) are a feature of plant genomes that has been largely unexplored despite their significant impact on plant phenotypic traits and local adaptation to abiotic and biotic stress. In this study, we employed woolly grape (Vitis retordii), a species native to the tropical and subtropical regions of East Asia with both coastal and inland habitats, as a valuable model for examining the impact of SVs on local adaptation. We assembled a haplotype‐resolved chromosomal reference genome for woolly grape, and conducted population genetic analyses based on whole‐genome sequencing (WGS) data from coastal and inland populations. The demographic analyses revealed recent bottlenecks in all populations and asymmetric gene flow from the inland to the coastal population. In total, 1,035 genes associated with plant adaptive regulation for salt stress, radiation, and environmental adaptation were detected underlying local selection by SVs and SNPs in the coastal population, of which 37.29% and 65.26% were detected by SVs and SNPs, respectively. Candidate genes such as FSD2, RGA1, and AAP8 associated with salt tolerance were found to be highly differentiated and selected during the process of local adaptation to coastal habitats in SV regions. Our study highlights the importance of SVs in local adaptation; candidate genes related to salt stress and climatic adaptation to tropical and subtropical environments are important genomic resources for future breeding programs of grapevine and its rootstocks. [ABSTRACT FROM AUTHOR]

Bacterial infections trigger a multifaceted interplay between inflammatory mediators and redox regulation. Recently, accumulating evidence has shown that redox signaling plays a significant role in immune initiation and subsequent immune cell functions. This review addresses the crucial role of the thioredoxin (Trx) system in the initiation of immune reactions and regulation of inflammatory responses during bacterial infections. Downstream signaling pathways in various immune cells involve thiol-dependent redox regulation, highlighting the pivotal roles of thiol redox systems in defense mechanisms. Conversely, the survival and virulence of pathogenic bacteria are enhanced by their ability to counteract oxidative stress and immune attacks. This is achieved through the reduction of oxidized proteins and the modulation of redox-sensitive signaling pathways, which are functions of the Trx system, thereby fortifying bacterial resistance. Moreover, some selenium/sulfur-containing compounds could potentially be developed into targeted therapeutic interventions for pathogenic bacteria. Taken together, the Trx system is a key player in redox regulation during bacterial infection, and contributes to host–pathogen interactions, offering valuable insights for future research and therapeutic development. [ABSTRACT FROM AUTHOR]

The interaction between influenza A virus (IAV) and host proteins is an important process that greatly influences viral replication and pathogenicity. PB2 protein is a subunit of viral ribonucleoprotein (vRNP) complex playing distinct roles in viral transcription and replication. BAG6 (BCL2-associated athanogene 6) as a multifunctional host protein participates in physiological and pathological processes. Here, we identify BAG6 as a new restriction factor for IAV replication through targeting PB2. For both avian and human influenza viruses, overexpression of BAG6 reduced viral protein expression and virus titers, whereas deletion of BAG6 significantly enhanced virus replication. Moreover, BAG6-knockdown mice developed more severe clinical symptoms and higher viral loads upon IAV infection. Mechanistically, BAG6 restricted IAV transcription and replication by inhibiting the activity of viral RNA-dependent RNA polymerase (RdRp). The co-Immunoprecipitation assays showed BAG6 specifically interacted with the N-terminus of PB2 and competed with PB1 for RdRp complex assembly. The ubiquitination assay indicated that BAG6 promoted PB2 ubiquitination at K189 residue and targeted PB2 for K48-linked ubiquitination degradation. The antiviral effect of BAG6 necessitated its N-terminal region containing a ubiquitin-like (UBL) domain (17-92aa) and a PB2-binding domain (124-186aa), which are synergistically responsible for viral polymerase subunit PB2 degradation and perturbing RdRp complex assembly. These findings unravel a novel antiviral mechanism via the interaction of viral PB2 and host protein BAG6 during avian or human influenza virus infection and highlight a potential application of BAG6 for antiviral drug development. Author summary: Influenza A virus (IAV) is a major public health threat worldwide. The viral polymerase subunit PB2 of IAV is not only responsible for transcription and replication of viral RNA but also acts as a key determinant for host adaptation, making it a key target of host defense system. In this study, we report BAG6 as a novel negative regulator of viral PB2 protein. It interacts with the N-terminus of PB2 and promotes PB2 ubiquitination at the K189 residue, which is highly conserved in all IAV subtypes, resulting in the competitive inhibition of RdRp assembly and the ubiquitination degradation of PB2. These findings emphasize the potent antiviral activity of BAG6 against both avian and human influenza viruses and provide a detailed insight to facilitate antivirals targeting PB2 protein. [ABSTRACT FROM AUTHOR]

In order to realize the high value utilization of solid and liquid wastes, extraction of vanadium from vanadium tailings with titanium dioxide waste acid was studied. The effects of leaching temperature, leaching time, solid mass to liquid volume ratio, waste acid concentration and other technological parameters on vanadium leaching rate were investigated by orthogonal experiments, and the optimal leaching conditions were determined. In order to further improve the vanadium leaching rate, the appropriate amount of leaching aid(fluorite) and oxidant(hydrogen peroxide) was discussed. The results show that the order of influence of the process parameters on vanadium leaching rate is leaching temperature>leaching time>solid mass to liquid volume ratio> titanium dioxide waste acid concentration. Under the optimum conditions of temperature of 80 °C, leaching time of 2 h, solid mass to liquid volume ratio of 1 : 5 and waste acid concentration of 5%, the vanadium leaching rate is about 53%. After adding 7% fluorite and 5% hydrogen peroxide, the vanadium leaching rate can be increased to 71. 09%. [ABSTRACT FROM AUTHOR]

The emerging epidemic of extended-spectrum β-lactamase-producing E. coli (ESBL-EC) is a global public health crisis. ESBL-EC infections are increasing worldwide and contribute to morbidity and mortality among newborn infants. However, the antimicrobial resistance characteristics and clonal transmission of maternal and neonatal ESBL-EC isolates need to be further deciphered.Materials and Methods: We performed phenotypic and genotypic characterization of 33 ESBL-EC isolates from pregnant women and newborn during 2019– 2020.Results: Minimum inhibitory concentrations of 17 antimicrobial agents showed that all isolates were multidrug-resistant (MDR) and had a resistance rate of 100% to ampicillin, and mild resistance to florfenicol, gentamicin, ceftazidime, and amoxicillin-clavulanate. Additionally, imipenem, meropenem, polymyxin, and tigecycline exhibited good activity against the tested ESBL-EC isolates with low MIC50 (0.06– 1 μg/mL) and MIC90 (0.06– 1 μg/mL). Whole genome sequencing indicated that ESBL-EC isolates contained diverse antimicrobial resistant genes (blaCTX-M, blaTEM, blaSHV, tetA, etc.) and toxin genes (ompA, csg, fimH, hybtA, etc.). blaCTX-M genes were the main ESBL genotype. ST1193 (18.2%) was the second most abundant ST among the ESBL-EC isolates (ST131 was the most common, with 30.3%), and this is the first report of its mother-to-infant colonization transmission in China.Conclusion: These findings revealed the occurrence of high-risk ST1193 clone among ESBL-EC isolates from pregnant women and newborn colonization in China. Further national or regional multicenter studies are needed to assess the dissemination and evolution of ESBL-EC ST1193 clone as a nosocomial pathogen in China. [ABSTRACT FROM AUTHOR]

Bending deflection is the main form of welding deformation,which is liable to occur in the Y-joint. Therefore,this paper investigated the strain distribution of Y-joint under the tensile test with digital image correlation（ DIC）. The study results showed that the strain distribution on the groove angle bisector is in approximate linear. On the inner side of groove angle bisector,the compressive strain is the largest,and on the outside of groove angle bisector the largest strain is tensile strain. The strain concentration is occurred in the groove area,however,the strain distribution curves are different with the areas. In order to reduce the strain concentration,the welding specimen was treated by annealing and the results showed that the strain distribution is more uniform compared with no annealing processing.

Panel pad bending is a critical process to improve the screen-to-body ratio of an active-matrix organic light-emitting diode (AMOLED) panel. The failure analysis of the metal wirings is the key to ensure the reliability of signal transmission when the pad be bent to the back of the panel. In the present work, the sub-modeling technique combined with the periodic boundary condition was used to simulate the stress distribution of the bending area of the pad. The progressive failure of bent metal wirings was investigated by the extended finite element method. It is proved to be rational to prevent the wirings damage if the interlayer dielectric is replaced by an organic layer. In order to reduce stress of metal wirings, it is a measure to replace the original ultraviolet (UV) curable adhesive with a higher-modulus UV adhesive. The simulated results also show that rectangular perforations can avoid the stress concentration caused by the holes compared with circular perforations. For better stress distribution of metal wirings, it is necessary to increase the lengths of the rectangular holes and decrease the widths of that to a certain extent, which is helpful for restraining crack propagation by means of low-stress zones and holes. [ABSTRACT FROM AUTHOR]

Heart failure with preserved ejection fraction (HFpEF) accounts for more than one-half of total heart failure cases, with a high prevalence and poor prognosis, especially in older and female patients. Patients with HFpEF are characterized by hypertension, left ventricular hypertrophy, and diastolic dysfunction, and the main symptoms are dyspnea and exercise intolerance. HFpEF is currently poorly studied, and pharmacological treatment for HFpEF is still underexplored. Accumulating clinical trials have shown that exercise could exert benefits on diastolic dysfunction and quality of life in patients with HFpEF. However, there is a high limitation for applying exercise therapy due to exercise intolerance in patients with HFpEF. Key effectors of exercise-protection could be novel therapeutic targets for developing drugs to prevent and treat HFpEF. In this review article, we provide an overview of the pathogenic factors, diagnostic methods, research animal models, the mechanisms of exercise-mediated cardiac protection, and current treatments for HFpEF. [ABSTRACT FROM AUTHOR]

Glycosylation is one of the most significant and abundant posttranslational modifications in mammalian cells. It mediates a wide range of biofunctions, including cell adhesion, cell communication, immune cell trafficking, and protein stability. Also, aberrant glycosylation has been associated with various diseases such as diabetes, Alzheimer's disease, inflammation, immune deficiencies, congenital disorders, and cancers. The alterations in the distributions of glycan and glycopeptide isomers are involved in the development and progression of several human diseases. However, the microheterogeneity of glycosylation brings a great challenge to glycomic and glycoproteomic analysis, including the characterization of isomers. Over several decades, different methods and approaches have been developed to facilitate the characterization of glycan and glycopeptide isomers. Mass spectrometry (MS) has been a powerful tool utilized for glycomic and glycoproteomic isomeric analysis due to its high sensitivity and rich structural information using different fragmentation techniques. However, a comprehensive characterization of glycan and glycopeptide isomers remains a challenge when utilizing MS alone. Therefore, various separation methods, including liquid chromatography, capillary electrophoresis, and ion mobility, were developed to resolve glycan and glycopeptide isomers before MS. These separation techniques were coupled to MS for a better identification and quantitation of glycan and glycopeptide isomers. Additionally, bioinformatic tools are essential for the automated processing of glycan and glycopeptide isomeric data to facilitate isomeric studies in biological cohorts. Here in this review, we discuss commonly employed MS‐based techniques, separation hyphenated MS methods, and software, facilitating the separation, identification, and quantitation of glycan and glycopeptide isomers. [ABSTRACT FROM AUTHOR]

Green food is well-known for its health benefits, environmental-friendliness, and safety. Current recommender systems used by e-commerce websites usually recommend products based on products' popularity or customers' ratings. However, users' reviews could be more representative of consumers' preferences. In addition, users' review time is not utilized. To reduce the recommendation bias, this study proposes a hybrid recommendation algorithm based on green food reviews and review time. The proposed algorithm combines a content-based recommendation algorithm with a user-based collaborative filtering approach, where affective values of reviews replace ratings and a time impact factor is considered. With the two classical evaluation indices of F1 and Mean Absolute Error (MAE), the experiments show that considering both reviews' sentiments and dynamic changes of individuals' preferences could improve recommendation effectiveness over three other algorithms, which provides a new reference direction for improving existing recommender systems on green food. [ABSTRACT FROM AUTHOR]

Due to the critical role of the glycome in organisms and its close connections with various diseases, much time and effort have been dedicated to glycomics-related studies in the past decade. To achieve accurate and reliable identification and quantification of glycans extracted from biological samples, several analysis methods have been well-developed. One commonly used methodology for the sample preparation of N-glycomics usually involves enzymatic cleavage by PNGase F, followed by sample purification using C18 cartridges to remove proteins. PNGase F and C18 cartridges are very efficient both for cleaving N-glycans and for protein removal. However, this method is most suitable for a limited quantity of samples. In this study, we developed a sample preparation method focusing on N-glycome extraction and purification from large-scale biological samples using acetone precipitation. The N-glycan yield was first tested on standard glycoprotein samples, bovine fetuin and complex biological samples, and human serum. Compared to C18 cartridges, most of the sialylated N-glycans from human serum were detected with higher abundance after acetone precipitation. However, C18 showed a slightly higher efficiency for protein removal. Using the unfiltered human serum as the baseline, around 97.7% of the proteins were removed by acetone precipitation, while more than 99.9% of the proteins were removed by C18 cartridges. Lastly, the acetone precipitation was applied to N-glycome extraction from egg yolks to demonstrate large-scale glycomics sample preparation. [ABSTRACT FROM AUTHOR]

Aiming to reduce the gap between in vitro and in vivo environment, a complex culture medium, Plasmax, was introduced recently, which includes nutrients and metabolites with concentrations normally found in human plasma. Herein, to study the influence of this medium on cellular behaviors, we utilized Plasmax to cultivate two cancer cell lines, including one breast cancer cell line, MDA-MB-231BR, and one brain cancer cell line, CRL-1620. Cancer cells were harvested and prepared for transcriptomics and proteomics analyses to assess the discrepancies caused by the different nutritional environments of Plasmax and two commercial media: DMEM, and EMEM. Total RNAs of cells were extracted using mammalian total RNA extract kits and analyzed by next-generation RNA sequencing; proteomics analyses were performed using LC-MS/MS. Gene oncology and pathway analysis were employed to study the affected functions. The cellular invasion and cell death were inhibited in MDA-MB-231BR cell line when cultured in Plasmax compared to DMEM and EMEM, whereas the invasion, migration and protein synthesis of CRL-1620 cell line were activated in Plasmax in relative to both commercial media. The expression changes of some proteins were more significant compared to their corresponding transcripts, indicating that Plasmax has more influence upon regulatory processes of proteins after translation. This work provides complementary information to the original study of Plasmax, aiming to facilitate the selection of appropriate media for in vitro cancer cell studies. [ABSTRACT FROM AUTHOR]

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Background: Histopathologic evaluation after surgery is the gold standard to evaluate treatment response to neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC). However, it cannot be used to guide organ‐preserving strategies due to poor timeliness. Purpose: To develop and validate a multiscale model incorporating radiomics and pathomics features for predicting pathological good response (pGR) of down‐staging to stage ypT0‐1N0 after nCRT. Study Type: Retrospective. Population: A total of 153 patients (median age, 55 years; 109 men; 107 training group; 46 validation group) with clinicopathologically confirmed LARC. Field Strength/Sequence: A 3.0‐T; fast spin echo T2‐weighted and single‐shot EPI diffusion‐weighted images. Assessment: The differences in clinicoradiological variables between pGR and non‐pGR groups were assessed. Pretreatment and posttreatment radiomics signatures, and pathomics signature were constructed. A multiscale pGR prediction model was established. The predictive performance of the model was evaluated and compared to that of the clinicoradiological model. Statistical Tests: The χ2 test, Fisher's exact test, t‐test, the minimum redundancy maximum relevance algorithm, the least absolute shrinkage and selection operator logistic regression algorithm, regression analysis, receiver operating characteristic curve (ROC) analysis, Delong method. P < 0.05 indicated a significant difference. Results: Pretreatment radiomics signature (odds ratio [OR] = 2.53; 95% CI: 1.58–4.66), posttreatment radiomics signature (OR = 9.59; 95% CI: 3.04–41.46), and pathomics signature (OR = 3.14; 95% CI: 1.40–8.31) were independent factors for predicting pGR. The multiscale model presented good predictive performance with areas under the curve (AUC) of 0.93 (95% CI: 0.88–0.98) and 0.90 (95% CI: 0.78–1.00) in the training and validation groups, those were significantly higher than that of the clinicoradiological model with AUCs of 0.69 (95% CI: 0.55–0.82) and 0.68 (95% CI: 0.46–0.91) in both groups. Data Conclusion: A model incorporating radiomics and pathomics features effectively predicted pGR after nCRT in patients with LARC. Evidence Level: 3 Technical Efficacy: Stage 4 [ABSTRACT FROM AUTHOR]

A complex physiological culture medium (Plasmax) was introduced recently, composed of nutrients and metabolites at concentrations normally found in human plasma to mimic the in vivo environment for cell line cultivation. As glycosylation has been proved to be involved in cancer development, it is necessary to investigate the glycan expression changes in media with different nutrients. In this study, a breast cancer cell line, MDA-MB-231BR, and a brain cancer cell line, CRL-1620, were cultivated in Plasmax and commercial media to reveal cell line glycosylation discrepancies prompted by nutritional environments. Glycomics analyses of cell lines were performed using LC-MS/MS. The expressions of multiple fucosylated N-glycans, such as HexNAc4Hex3DeoxyHex1 and HexNAc5Hex3DeoxyHex1, derived from both cell lines exhibited a significant increase in Plasmax. Among the O-glycans, significant differences were also observed. Both cell lines cultivated in EMEM had the lowest amounts of O-glycans expressed. The original work described the development of Plasmax, which improves colony formation, and resulted in transcriptomic and metabolomic alterations of cancer cell lines, while our results indicate that Plasmax can significantly impact protein glycosylation. This study also provides information to guide the selection of media for in vitro cancer cell glycomics studies. [ABSTRACT FROM AUTHOR]

Glycosylation is known as a critical biological process that can largely affect the properties and the functions of proteins. Glycan isomers have been shown to be involved in a variety of disease progressions. However, the separation and identification of glycan isomers has been a challenge for years due to the microheterogeneity of glycan isomeric structures. Therefore, effective and stable techniques have been investigated over the last few decades to improve isomeric separations of glycans. RPLC has been widely used in biomolecule analysis because of its extraordinary reproducibility and reliability in retention time and separation resolution. However, so far, no studies have achieved high resolution of glycan isomers using this technique. In this study, we focused on further boosting the isomeric separation of permethylated glycans using a 500 mm reversed-phase LC column. To achieve better resolutions on permethylated glycans, different LC conditions were optimized using glycan standards, including core- and branch-fucosylated N-glycan isomers and sialic acid linked isomers, which were both successfully separated. Then, the optimal separation strategy was applied to achieve separations of N- and O-glycan isomers derived from model glycoproteins, including bovine fetuin, ribonuclease B and κ-casein. Baseline separations were observed on multiple sialylated linkage isomers. However, the separation performance of high-mannose isomers needs further improvement. The reproducibility and stability of this long C18 column was also tested by doing run-to-run, day-to-day and month-to-month comparisons of retention times on multiple glycans and the %RSD was found less than 0.92%. Finally, we applied this approach to separate glycan isomers derived from complex biological samples, including blood serum and cell lines, where baseline separations were attained on several isomeric structures. Compared to the separation efficiency of PGC and MGC columns, the RPLC C18 column provides lower resolution but more robust reproducibility, which makes it a good complementary alternative for isomeric separations of glycans. [ABSTRACT FROM AUTHOR]