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Lysine succinylation (Ksu) has recently emerged as a protein modification that regulates diverse functions in various biological processes. However, the systemically and precise role of lysine succinylation in erythropoiesis remains to be fully elucidated. In this study, we noted a prominent increase of succinyl-CoA and lysine succinylation during human erythroid differentiation. To explore the functional significance of succinylation, we inhibited succinylation by either knock downing key succinyltransferases or overexpressing desuccinylases. Succinylation inhibition led to suppressed cell proliferation, increased apoptosis, and disrupted erythroid differentiation. In vivo overexpression of the desuccinylases SIRT5 delayed erythroid differentiation. Furthermore, integrative proteome and succinylome analysis identifies 939 succinylated proteins with 3,562 Ksu sites, distributed across various cellular compartments and involved in multiple cellular processes. Significantly, inconsistencies between protein expression levels and succinylation levels were observed, indicating that the succinylation of certain proteins may function independently of expression. Mechanistically, we implicated KAT2A-mediated succinylation of histone H3 K79, leading to chromatin remodeling and subsequently erythropoiesis regulation. Specially, we identified CYCS as a key regulator of erythropoiesis, which depends on its succinylation sites K28/K40. Taken together, our comprehensive investigation of the succinylation landscape during erythropoiesis provides valuable insights into its regulatory role and offer potential implications for erythroid-related diseases.

Abstract High thermal conductive polymers have become more important because equipment requires high performance, high-energy density, and high integration. There are different strategies to make high thermal conductive polymers, among which is the synthesis of polymers in the liquid crystal phase. However, the thermal conductivity of such material is rarely beyond 1 W m−1 K−1 because of the disordered molecular directionality. The disordered directionality between crystal zones limits the thermal conductivity in a specific direction. Here, we show a method for unifying the direction of crystal zones by applying an external electric field on the liquid crystal monomers. Meanwhile, by exposing the transparent equipment and specially designed photopolymerisable monomer in UV light, the liquid crystal monomer is in situ polymerised into a liquid crystal polymer with a high intrinsic thermal conductivity of 1.02 W m−1 K−1. The molecular alignment was characterised and resulted in the resultant high conductivity.

The importance evaluation of power grid transmission lines is crucial for preventing catastrophic grid failures, enhancing grid resilience, and ensuring the safe and stable operation of the power system. To address the limitations in existing transmission line evaluation methods, such as reliance on single evaluation metrics, insufficient consideration of information transmission between adjacent lines, and the impact of line failures on system load loss, this paper proposes a comprehensive evaluation method based on multidimensional information feature mapping. First, evaluation metrics are established from three dimensions—power transmission characteristics, grid network structure, and resilience improvement—each reflecting the importance of transmission lines from different perspectives. Then, a hybrid weighting method is introduced, combining subjective and objective weights through a game theory approach to calculate the comprehensive weights, enabling the multidimensional information-based importance evaluation of transmission lines. Finally, an improved network efficiency index, representing the current operational performance of the grid, is developed to validate the proposed evaluation method. A simulation analysis using the IEEE-39 bus test system verifies the feasibility and accuracy of the proposed approach.

Exploring the effects of seasonal variation on the gut microbiota of cold-water fish plays an important role in understanding the relationship between seasonal variation and cold-water fish. Gut samples of cold-water fish and environmental samples were collected during summer and winter from the lower reaches of the Yalong River. The results of the 16S rRNA sequencing showed that significant differences were identified in the composition and diversity of gut bacteria of cold-water fish. Co-occurrence network complexity of the gut bacteria of cold-water fish was higher in summer compared to winter (Sum: nodes: 256; edges: 20,450; Win: nodes: 580; edges: 16,725). Furthermore, from summer to winter, the contribution of sediment bacteria (Sum: 5.3%; Win: 23.7%) decreased in the gut bacteria of cold-water fish, while the contribution of water bacteria (Sum: 0%; Win: 27.7%) increased. The normalized stochastic ratio (NST) and infer community assembly mechanisms by phylogenetic bin-based null model analysis (iCAMP) showed that deterministic processes played a more important role than stochastic processes in the microbial assembly mechanism of gut bacteria of cold-water fish. From summer to winter, the contribution of deterministic processes to gut bacteria community assembly mechanisms decreased, while the contribution of stochastic processes increased. Overall, these results demonstrated that seasonal variation influenced the gut bacteria of cold-water fish and served as a potential reference for future research to understand the adaptation of fish to varying environments.

The hybrid yellow catfish exhibits advantages over pure yellow catfish in terms of fast growth, fast development, a high feeding rate, and strong immunity; additionally, it is almost sterile, thus ensuring the conservation of the genetic stock of fish populations. To investigate the sterility mechanism in hybrid yellow catfish (P. fulvidraco (♀) × P. vachelli (♂)), the mRNA and miRNA of the gonads of P. fulvidraco, P. vachelli, and a hybrid yellow catfish were analyzed to characterize the differentially expressed genes; this was carried out to help establish gene expression datasets to assist in the further determination of the mechanisms of genetic sterility in hybrid yellow catfish. In total, 1709 DEGs were identified between the hybrid and two pure yellow catfishes. A KEGG pathway analysis indicated that several genes related to reproductive functions were upregulated, including those involved in the cell cycle, progesterone-mediated oocyte maturation, and oocyte meiosis, and genes associated with ECM–receptor interaction were downregulated. The spermatogenesis-related GO genes CFAP70, RSPH6A, and TSGA10 were identified as being downregulated DEGs in the hybrid yellow catfish. Sixty-three DEmiRNAs were identified between the hybrid and the two pure yellow catfish species. The upregulated DEmiRNAs ipu-miR-194a and ipu-miR-499 were found to target the spermatogenesis-related genes CFAP70 and RSPH6A, respectively, playing a negative regulatory role, which may underscore the miRNA–mRNA regulatory mechanism of sterility in hybrid yellow catfish. The differential expression of ipu-miR-196d, ipu-miR-125b, and ipu-miR-150 and their target genes spidr, cep85, and kcnn4, implicated in reproductive processes, was verified via qRT-PCR, consistent with the transcriptome sequencing expression trends. This study provides deep insights into the mechanism of hybrid sterility in vertebrate groups, thereby contributing to achieving a better understanding and management of fish conservation related to hybrid sterility.

A new type of multiphase nanoparticle-reinforced TiAl matrix composites ((Ti2AlC + Al2O3)p/TiAl composites) was successfully prepared by vacuum hot-pressing sintering using Ti powder and Al powder, which were ball-milled with different contents of stearic acid (CH3(CH2)16COOH). The component, microstructure, reaction mechanism, and mechanical properties were studied. The results indicated that the composites prepared by adding stearic acid as a process control agent during the ball-milling process not only contained γ-TiAl and α2-Ti3Al phases but also Ti2AlC and Al2O3 phases. The results of SEM and TEM showed that the composites were composed of equiaxed TiAl and Ti3Al grains, and the Ti2AlC and Al2O3 particles were mainly distributed along the TiAl grain boundary in chain form, which can effectively reduce the TiAl grain size. Through the room-temperature compression test, the maximum compression stress was significantly improved in those composites that added the stearic acid, due to the reinforcement particles. The maximum compression stress was 1590 MPa with a 24.3% fracture strain. In addition, the generated crack deflection and Ti2AlC and Al2O3 particles could also enhance the toughness of the TiAl alloy. (Ti2AlC + Al2O3)p/TiAl composites generated by adding stearic acid played a key role in improving the mechanical properties of the TiAl matrix.

Abstract In this study, the Zn nanoparticles were synthesized using the peel extract of Citrus aurantium. The nanoparticles were characterized by different chemical techniques including UV‐Vis. and FT‐IR spectroscopy, and SEM technique. The results revealed a spherical shape with an average size of 41.17 nm was identified for the green‐synthesized nanoparticles. In the antioxidant test, the IC50 of nanoparticles and butylated hydroxytoluene (BHT) against DPPH free radicals were 115 and 96 μg/mL, respectively. In the cellular and molecular part of the recent study, the treated cells with nanoparticles were assessed by the MTT assay for 48 h about the cytotoxicity and anti‐human bone cancer properties on normal (HUVEC) and cancer cell lines, that is, A‐673 and HS‐729. The IC50 of nanoparticles were 278 and 256 μg/mL against A‐673 and HS‐729 cell lines, respectively. The viability of malignant cell lines reduced dose‐dependently in the presence of Zn nanoparticles. It seems that the anti‐cancer effect of recent nanoparticles is due to their anti‐oxidant effects. After evaluating the effectiveness of this formulation in clinical trial researches, it can be a good alternative to chemotherapy drugs.

Bethlem myopathy (BM) is a disease that is caused by mutations in the collagen VI genes. It is a mildly progressive disease characterized by proximal muscle weakness and contracture of the fingers, the wrist, the elbow, and the ankle. BM is an autosomal dominant inheritance that is mainly caused by dominant COL6A1, COL6A2, or COL6A3 mutations. However, a few cases of collagen VI mutations with bilateral facial weakness and Beevor's sign have also been reported. This study presents a 50-year-old female patient with symptoms of facial weakness beginning in childhood and with the slow progression of the disease with age. At the age of 30 years, the patient presented with asymmetrical proximal muscle weakness, and the neurological examination revealed bilateral facial weakness and a positive Beevor's sign. Phosphocreatine kinase was slightly elevated with electromyography showing myopathic changes and magnetic resonance imaging (MRI) of the lower limb muscles showing the muscle MRI associated with collagen VI (COL6)-related myopathy (COL6-RM). The whole-genome sequencing technology identified the heterozygous mutation c.6817-2(IVS27)A>G in the COL6A3 gene, which was in itself a novel mutation. The present study reports yet another case of BM, which is caused by the recessive COL6A3 intron variation, widening the clinical spectrum and genetic heterogeneity of BM.

Abstract FDA-approved anti-PD-L1 antibody drug Atezolizumab is a human IgG1 without glycosylation by an N297A mutation. Aglycosylation of IgG1 has been used to completely remove the unwanted Fc-mediated functions such as antibody-dependent cytotoxicity (ADCC). However, aglycosylated Atezolizumab is very unstable and easy to form aggregation, which causes quick development of anti-drug antibody (ADA) in 41% of Atezolizumab-treated cancer patients, eventually leading to loss of efficacy. Here, we report the development of the anti-PD-L1 antibody drug Maxatezo, a glycosylated version of Atezolizumab, with no ADCC activity, better thermo-stability, and significantly improved anti-tumor activity in vivo. Using Atezolizumab as the starting template, we back-mutated A297N to re-install the glycosylation, and inserted a short, flexible amino acid sequence (GGGS) between G237 and G238 in the hinge region of the IgG1 heavy chain. Our data shows that insertion of GGGS, does not alter the anti-PD-L1′s affinity and inhibitory activity, while completely abolishing ADCC activity. Maxatezo has a similar glycosylation profile and expression level (up to 5.4 g/L) as any normal human IgG1. Most importantly, Maxatezo’s thermal stability is much better than Atezolizumab, as evidenced by dramatic increases of Tm1 from 63.55 °C to 71.01 °C and Tagg from 60.7 °C to 71.2 °C. Furthermore, the levels of ADA in mice treated with Maxatezo were significantly lower compared with animals treated with Atezolizumab. Most importantly, at the same dose (10 mg/kg), the tumor growth inhibition rate of Maxatezo was 98%, compared to 68% for Atezolizumab.

A highly thermally conductive heat spreader for applications in electronic devices is becoming increasingly demanding, and therefore the removal of excess heat requires an efficient heat dissipating device. Boron nitride nanosheets (BNNSs) were prepared as thermally conductive fillers using hexagonal boron nitride (h-BN) powder as raw material by a water exfoliation method. A composite film was prepared by vacuum filtration using cellulose nanofibers (CNFs) as the substrate with an in-plane thermal conductivity (TC) of 82.4 W m−1 K−1, thermal conductivity enhancement increasing by 9,486% compared to pure cellulose film. Thus, CNF/BNNS composite films are promising as effective thermal interface materials (TIMs) in electronic devices and electronic component applications.

Infective endocarditis (IE) usually presents with nonspecific signs and symptoms, which delay diagnosis and proper treatment. Here, we describe a patient with initial clinical and radiological features compatible with neurocysticercosis who was later found to have IE. Furthermore, the patient course was complicated by multiple neurological complications (brain abscess, meningitis, infected intracranial aneurysm, subarachnoid hemorrhage and hemorrhage), and patient ultimately deceased. To our knowledge, an IE case mimicking neurocysticercosis and progressing with prominent and complicated neurological manifestations has not been previously reported. We therefore describe the challenges of neurocysticercosis diagnosis based on serum ELISA and radiological findings.For patient diagnosed as neurocysticercosis, clinical follow-up is recommended and presence of systemic symptoms should be red flags for another underlying disease.

Cancer incidence and mortality are rapidly increasing worldwide; therefore, effective therapies are required in the current scenario of increasing cancer cases. Polysaccharides are a family of natural polymers that hold unique physicochemical and biological properties, and they have become the focus of current antitumour drug research owing to their significant antitumour effects. In addition to the direct antitumour activity of some natural polysaccharides, their structures offer versatility in synthesizing multifunctional nanocomposites, which could be chemically modified to achieve high stability and bioavailability for delivering therapeutics into tumor tissues. This review aims to highlight recent advances in natural polysaccharides and polysaccharide-based nanomedicines for cancer therapy.

Impervious surfaces are key indicators for urbanization monitoring and watershed degradation assessment over space and time. However, most empirical studies only extracted impervious surface from spatial, temporal or spectral perspectives, paying less attention to integrating multiple dimensions in acquiring continuous changes in impervious surfaces. In this study, we proposed a neighborhood-based spatio-temporal filter (NSTF) to obtain the continuous change information of impervious surfaces from multi-temporal Landsat images in the Qinhuai River Basin (QRB), Jiangsu, China from 1988–2017, based on the results from semi-automatic decision tree classification. Moreover, we used the expansion intensity index (EII) and the landscape extension index (LEI) to further characterize the spatio-temporal characteristics of impervious surfaces on different spatial scales. The preliminary results showed that the overall accuracies of the final classification were about 95%, with the kappa coefficients ranging between 0.9 and 0.96. The QRB underwent rapid urbanization with the percentage of the impervious surfaces increasing from 2.72% in 1988 to 25.6% in 2017. Since 2006, the center of urbanization expansion was shaped from the urban built-up areas of Nanjing and Jiangning to non-urban built-up areas of the Jiangning, Lishui, and Jurong districts. The edge expansion occupied 73% on average among the different landscape expansion types, greatly beyond outlying (12%) and infilling (15%). The window size in the NSTF has a direct impact on the subsequent analysis. Our research could provide decision-making references for future urban planning and development in the similar basins.

The rapid development of chip technology has all put forward higher requirements for highly thermally conductive materials. In this work, a new type of material of Fishbone-like silicon carbide (SiC) material was used as the filler in a polyvinylidene fluoride (PVDF) matrix. The silicon carbide/polyvinylidene fluoride (SiC/PVDF) composites were successfully prepared with different loading by a simple mixing method. The thermal conductivity of SiC/PVDF composite reached 0.92 W m−1 K−1, which is 470% higher than that of pure polymer. The results show that using the filler with a new structure to construct thermal conductivity networks is an effective way to improve the thermal conductivity of PVDF. This work provides a new idea for the further application in the field of electronic packaging.

ObjectivesLumbar spinal stenosis (LSS) refers to a narrowing of the space within the spinal canal, which can occur at any level but is most common in the lumbar spine. Open laminectomy and minimally invasive laminectomy (MIL) procedures are the most common surgical gold standard techniques for treating LSS. This study aims to review clinical and biomechanical literature to draw comparisons between open laminectomy and various MIL techniques. The MIL variation comprises microendoscopic decompression laminotomy, unilateral partial hemilaminectomy, and microendoscopic laminectomy.MethodsA review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We reviewed 25 clinical, 6 finite element, and 3 cadaveric studies associated with treating LSS. We reviewed literature that discusses factors such as operation time, length of hospital stay, postoperative complications, reoperation rate, effect on elderly patients, patients’ satisfaction, and adjacent segment disease degeneration for the clinical studies, whereas the range of motion (ROM), von Mises stresses, and stability was compared in biomechanical studies.ResultsMIL involves less bone and ligament removal, resulting in shorter hospital stays and lower reoperation and complication rates than open laminectomy. It improves the quality of health-related living standards and reduces postoperative pain. Biomechanical studies suggest that laminectomy and facetectomy increase annulus stress and ROM, leading to segmental instability.ConclusionAlthough theoretically, MIL means less tissue injury, pain, and faster recovery in the short term, the long-term results depend on the adequacy of the decompression procedure and tend to be independent of MIL or open laminectomy.