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Abstract Neuroblastoma, the deadliest solid tumor in children, exhibits alarming mortality rates, particularly among high-risk cases. To enhance survival rates, a more precise risk stratification for patients is imperative. Utilizing proteomic data from 34 cases with or without N-Myc amplification, we identified 28 differentially expressed ubiquitination-related proteins (URGs). From these, a prognostic signature comprising 6 URGs was constructed. A nomogram incorporating clinical-pathological parameters yielded impressive AUC values of 0.88, 0.93, and 0.95 at 1, 3, and 5 years, respectively. Functional experiments targeting the E3 ubiquitin ligase FBXO42, a component of the prognostic signature, revealed its TP53-dependent promotion of neuroblastoma cell proliferation. In conclusion, our ubiquitination-related prognostic model robustly predicts patient outcomes, guiding clinical decisions. Additionally, the newfound pro-proliferative role of FBXO42 offers a novel foundation for understanding the molecular mechanisms of neuroblastoma.

Abstract Hydrophobicity enhancement of metal-free leather, which is crucial for improving its comprehensive performance, can be achieved by using amphiphilic copolymer retanning agents. However, the relationship between the sequential structure and the hydrophobic modification effect of amphiphilic copolymers remains unclear. Herein, an amphiphilic block copolymer was synthesized using stearyl methacrylate and 2-(dimethylamino)ethyl methacrylate via atom transfer radical polymerization, and the corresponding random copolymer with similar monomer compositions and molecular weights was prepared for comparison. The aggregation behavior of block and random copolymers was investigated. DLS and TEM results indicate that the block copolymer exhibits a larger aggregate size than the corresponding random copolymer. Molecular dynamics simulations suggest that the block copolymer aggregate exhibit a thicker hydrophilic shell and more concentrated distribution of cationic DMA block than the random copolymer aggregate. Subsequently, the block and random copolymers were used for the hydrophobic modification of metal-free tanned collagen fibers (CFs). The block copolymer shows superior binding capacity to CFs than the random one because of its larger size and more concentrated charge distribution. Hence, the block copolymer can form a dense and uniform hydrophobic film on the surface of collagen fibrils and endow CFs with higher hydrophobicity than the random one. This work provides theoretical guidance for modulating the hydrophobicity of CFs by tailoring the sequential structure of amphiphilic copolymers, which is expected to inspire the manufacturing of high-performance metal-free leather. Graphical Abstract

The tumor metastasis suppressor gene CD82/KAI1 has been demonstrated to impact human trophoblast invasion and migration. Communication between trophoblasts and decidual stromal cells plays a crucial role in controlling the normal invasiveness of trophoblasts. However, whether CD82/KAI1 is involved in decidualization and what role it plays remain unclear. CD82/KAI1 demonstrates specific spatiotemporal expression patterns in stromal cells undergoing decidualization during pregnancy. This is observed in both naturally pregnant females post-implantation and pseudopregnant mice undergoing induced decidualization, as detected through in situ hybridization and immunofluorescence. CD82/KAI1 expression showed a significant time-dependent increase in cultured stromal cells after 24 and 48 h of progesterone (P4) and estrogen (E2) treatment. This was accompanied by a notable upregulation of decidualization markers, including cyclin D3 and PR. After transducing stromal cells with the adenovirus-overexpressing CD82/KAI1 for 48 h, the expression of cyclin D3 protein increased. Meanwhile, there was an attenuated expression of CD82/KAI1 due to an adenovirus siRNA knockdown, whereas cyclin D3 and PR expressions were not affected. Our findings suggest a potential role of CD82/KAI1 in regulating the process of decidualization, providing insights into stromal cell differentiation.

BackgroundMAPT variants are a known cause of frontotemporal dementia and Parkinsonian syndrome, of which progressive supranuclear palsy syndrome (PSP) is a rare manifestation.ObjectiveTo report a novel MAPT variant in a PSP pedigree with autosomal dominant inheritance pattern, and to produce a literature review of PSP patients with MAPT variants.MethodsA comprehensive clinical, genetic, and molecular neuroimaging investigation was conducted on a 61 years-old female proband diagnosed with PSP. We also collected the clinical presentation data and history of the patient’s pedigree, and performed further genetic analysis of 4 relatives, from two generations, with and without symptoms.ResultsThe proband exhibited typical clinical manifestation of PSP. A cranial MRI revealed midbrain atrophy, and an FDG-PET scan suggested hypo-metabolic changes in caudate nucleus, left prefrontal lobe, both temporal poles, and midbrain. 18F-florzolo-tau-PET revealed tau-protein deposits in the thalamus and brainstem bilaterally. A gene test by whole-exome sequencing identified a novel MAPT variant [NM_005910.6, exon 11, c.1024G > A (p.E342K)], and the same variant was also identified in one affected relative and one asymptomatic relative, a probable pre-symptomatic carrier.ConclusionThe PSP pedigree caused by the novel MAPT (E342K) variant, expanded the mutational spectrum of MAPT.

Color characteristics are a crucial indicator of green tea quality, particularly in needle-shaped green tea, and are predominantly evaluated through subjective sensory analysis. Thus, the necessity arises for an objective, precise, and efficient assessment methodology. In this study, 885 images from 157 samples, obtained through computer vision technology, were used to predict sensory evaluation results based on the color features of the images. Three machine learning methods, Random Forest (RF), Support Vector Machine (SVM) and Decision Tree-based AdaBoost (DT-AdaBoost), were carried out to construct the color quality evaluation model. Notably, the DT-Adaboost model shows significant potential for application in evaluating tea quality, with a correct discrimination rate (CDR) of 98.50% and a relative percent deviation (RPD) of 14.827 in the 266 samples used to verify the accuracy of the model. This result indicates that the integration of computer vision with machine learning models presents an effective approach for assessing the color quality of needle-shaped green tea.

As an indispensable part of large Computer Numerical Control machine tool, rolling bearing faults diagnosis is particularly important. However, due to the imbalanced distribution and partially missing of collected monitoring data, such diagnostic issue generally emerging in manufacturing industry is still hardly to be solved. Thus, a multilevel recovery diagnosis model for rolling bearing faults from imbalanced and partially missing monitoring data is formulated in this paper. Firstly, a regulable resampling plan is designed to handle the imbalanced distribution of data. Secondly, a multilevel recovery scheme is formed to deal with partially missing. Thirdly, an improved sparse autoencoder based multilevel recovery diagnosis model is built to identify the health status of rolling bearings. Finally, the diagnostic performance of the designed model is verified by artificial faults and practical faults tests, respectively.

[Introduction] With the rapid development of domestic battery energy storage market, more and more manufacturers have joined in the battery energy storage field, making the industry competition increasingly fierce. Chinese enterprises urgently need to explore a new market overseas. [Method] By collecting, sorting and analyzing the data of India's wind power and photovoltaic power industry, the capacity of its supporting battery energy storage market was calculated, the development status of its battery energy storage market, the bidding requirements of energy storage projects, and the advantages of Chinese enterprises were analyzed. [Result] The results of calculation show that the battery energy storage market in India's wind power and photovoltaic industry has great potential, and Chinese enterprises benefit from the rapid development of domestic battery energy storage technology, and have great advantages in developing battery energy storage business in India, but also face great challenges. [Conclusion] The research results provide a reference for Chinese enterprises to develop battery storage business in India.

Abstract Pancreatic cancer (PC) remains one of the most lethal human malignancies worldwide. Due to the insidious onset and the rapid progression, most patients with PC are diagnosed at an advanced stage rendering them inoperable. Despite the development of multiple promising chemotherapeutic agents as recommended first‐line treatment for PC, the therapeutic efficacy is largely limited by unwanted drug resistance. Recent studies have identified exosomes as essential mediators of intercellular communications during the occurrence of drug resistance. Understanding the underlying molecular mechanisms and complex signaling pathways of exosome‐mediated drug resistance will contribute to the improvement of the design of new oncologic therapy regimens. This review focuses on the intrinsic connections between the chemoresistance of PC cells and exosomes in the tumor microenvironment (TME).

Pancreatic cancer remains one of the most lethal malignancies worldwide. The combination of the first-line standard agent gemcitabine (GEM) with the molecular-targeted drug erlotinib (Er) has emerged as a promising strategy for pancreatic cancer treatment. However, the clinical benefit from this combination is still far from satisfactory due to the unfavorable drug antagonism and the fibrotic tumor microenvironment. Herein, we propose a membrane-camouflaged dual stimuli-responsive delivery system for the co-delivery of GEM and Er into pancreatic cancer cells and tissues to block the antagonism, as well as reshapes profibrotic tumor microenvironment via simultaneous delivery of small interference RNA (siRNA) for synergistic pancreatic cancer treatment. This “all-in-one” delivery system exhibits sensitive GSH and pH-dependent drug release profiles and enhances the inhibitory effects on the proliferation and migration of tumor cells in vitro. Excitingly, the systemic injection of such a biomimetic drug co-delivery system not only resulted in superior inhibitory effects against orthotopic pancreatic tumor and patient-derived tumor (PDX), but also greatly extended the survival rate of tumor-bearing mice. Our findings provide a promising therapeutic strategy against pancreatic cancer through the enhanced synergistic effect of target therapy, chemotherapy and anti-fibrotic therapy, which represents an appealing way for pancreatic cancer treatment.

Abstract Metal‐free room‐temperature phosphorescence (RTP) materials are of great significance for many applications; however, they usually exhibit low efficiency and weak intensity. This article reports a new strategy for the preparation of a high‐efficiency and strong RTP materials from crystalline thermal‐annealed carbon dots (CDs) and boric acid (BA) composite (g‐t‐CD@BA) through grinding‐induced amorphous to crystallization transition. Amorphous thermal‐annealed CDs and BA composite (t‐CD@BA) is prepared following a thermal melting and super‐cooling route, where the CDs are fully dispersed in molten BA liquid and uniformly frozen in an amorphous thermal annealed BA matrix after super‐cooling to room temperature. Upon grinding treatment, the fracture and fragmentation caused by grinding promote the transformation of the high‐energy amorphous state to the lower energy crystalline counterparts. As a result, the CDs are uniformly in situ embedded in the BA crystal matrix. This method affords maximum uniform embedding of the CDs in the BA crystals, decreases nonradiative decay, and promotes intersystem crossing by restraining the free vibration of the CDs, thus producing strong RTP materials with the highest reported phosphorescence quantum yield (48%). Remarkably, RTP from g‐t‐CD@BA powder is strong enough to illuminate items with a delay time exceeding 9 s.

Serotonin (5-HT) is primarily distributed in the gastrointestinal and central nervous systems, where it plays a crucial role in regulating various physiological functions such as digestion, reproduction and establishing animal emotions. 5-HT is an effective oxytocin widely used in molluscan aquaculture, and its physiological functions are performed by binding to corresponding 5-HT receptors (5-HTRs). In this study, seven 5-HTR genes of Sinonovacula constricta (Sc5-HTRs) were identified and analyzed, and they were designated as Sc5-HT1A, Sc5-HT1D, Sc5-HT2-1, Sc5-HT2-2, Sc5-HT2-3, Sc5-HT4 and Sc5-HT6. Phylogenetic analysis showed that the seven Sc5-HTRs were conserved among mollusks, and the Sc5-HTRs were all transmembrane proteins. The seven Sc5-HTR genes were distributed on chromosome 1, 2, 13 and 14. After injecting 5-HT, there was a significant increase in mRNA expression levels of Sc5-HT1A (p < 0.05) and Sc5-HT2-3 (p < 0.01), while Sc5-HT4 decreased significantly (p < 0.01) compared to control groups which might be effective 5-HT receptors. Furthermore, two of the receptors (Sc5-HT2-3 and Sc5-HT4) were expressed in the circadian rhythm patterns, indicating their potential influence on the nocturnal spawning of S. constricta. Overall, these findings provide a theoretical basis for understanding the structures and functions of 5-HTR gene family members, and may facilitate the artificial propagation of mollusks.

Abstract Amphoteric polymer can be used as retanning agent in leather manufacture. It is particularly useful in chrome-free tanning systems since it can regulate the charge properties of chrome-free leather and enhance the fixation of anionic post-tanning chemicals in leather. However, the aggregation and precipitation of amphoteric polymer retanning agents around the isoelectric point (pI) hinder their wide application. Herein, we synthesized five amphoteric acrylic polymers (AAPs) by free radical copolymerization with acrylic acid and five different cationic acrylic monomers. The effect of cationic monomer structure on the aggregation behavior of AAPs was investigated. The aggregation of AAPs in aqueous solution showed pH and concentration dependence. Light scattering analysis showed that Poly (AA-co-MAPTAC) and Poly (AA-co-DMAPMA) were in the shape of coiled linear flexible chains with small particle size (Rg 7.6 nm and 14.8 nm, respectively) near the pI. However, Poly (AA-co-DAC), Poly (AA-co-DMC) and Poly (AA-co-DMAEMA) were in the shape of hollow spheres and exhibited serious aggregation. Quantum chemical calculations suggested that the amide groups in the cationic monomers MAPTAC and DMAPMA enhanced the nucleophilicity of AAPs. Thus the corresponding AAPs could carry a large number of cationic charges to slow their aggregation when the pH just climbed over the pI. The results are expected to provide theoretical reference for the synthesis and widespread application of AAPs.

The spatter formation process was observed by high-speed imaging during the full-penetration laser welding (FPLW) process of 4 mm-thick TC4 alloy plates. The effects of process parameters on spatter formation were studied. The results showed that the process parameters have obvious effects on the fluid flow characteristics in the melt pool and the dynamic behaviors of metal vapor in the keyhole, which and then affects the spatter behaviors. When using low-power and low-speed parameters, the fluid flow in the melt pool is unstable. When the melt flow impacts the keyhole, the keyhole opening diameter shrinks instantly, resulting in an immediate increase in the metal vapor eruption velocity at the keyhole opening and leading to the formation of weld spatter with a small size and high flying speed. When using high-power and high-speed parameters, a large amount of metal vapor erupts at high velocity from the keyhole opening transiently, resulting in the formation of a higher liquid column on the keyhole wall. The liquid column fractures to form weld spatter with a large size and low flying speed. When the pressure of the metal vapor in the keyhole is too large, the surface tension of the liquid metal under the keyhole cannot withstand it, causing an explosion on the backside of the melt pool. During the explosion, a large amount of spatter and plasma is ejected from the keyhole exit, and the plasma plume above the melt pool is weakened.

BackgroundLung adenocarcinoma (LUAD) is the most common respiratory globallywith a poor prognosis. Lipid metabolism is extremely important for the occurrence and development of cancer. However, the role of genes involved in lipid metabolism in LUAD development is unclear. We aimed to identify the abnormal lipid metabolism pathway of LUAD, construct a novel prognostic model of LUAD, and discover novel biomarkers involved in lipid metabolism in LUAD.MethodsBased on differentially expressed genes involved in lipid metabolism in LUAD samples from The Cancer Genome Atlas (TCGA), abnormal lipid metabolism pathways in LUAD were analyzed. The lasso penalized regression analysis was performed on the TCGA cohort (training set) to construct a risk score formula. The predictive ability of the risk score was validated in the Gene Expression Omnibus (GEO) dataset (validation set) using Kaplan-Meier analysis and ROC curves. Finally, based on CRISPR gene editing technology, hematopoietic prostaglandin D synthase (HPGDS) was knocked out in A549 cell lines, the changes in lipid metabolism-related markers were detected by western blotting, and the changes in cell migration were detected by transwell assay.ResultsBased on the differential genes between lung cancer tissue and normal tissue, we found that the arachidonic acid metabolism pathway is an abnormal lipid metabolism pathway in both lung adenocarcinoma and lung squamous cell carcinoma. Based on the sample information of TCGA and abnormally expressed lipid metabolism-related genes, a 9-gene prognostic risk score was successfully constructed and validated in the GEO dataset. Finally, we found that knockdown of HPGDS in A549 cell lines promoted lipid synthesis and is more invasive than in control cells. Rescue assays showed that ACSL1 knockdown reversed the pro-migration effects of HPGDS knockdown. The knockdown of HPGDS promoted migration response by upregulating the expression of the lipid metabolism key enzymes ACSL1 and ACC.ConclusionThe genes involved in lipid metabolism are associated with the occurrence and development of LUAD. HPGDS can be a therapeutic target of a potential lipid metabolism pathway in LUAD, and the therapeutic target of lipid metabolism genes in LUAD should be studied further.

Mechano-luminescent materials that exhibit distinct luminescence responses to force stimuli are urgently anticipated in view of application needs in the fields of sensing, anti-counterfeiting, optoelectronic devices, etc. However, most of the reported materials normally exhibit force-induced changes in luminescent intensity, whereas materials that possess force-induced color-variable luminescence remain rarely reported. Herein, for the first time, a novel mechanical force-induced color-variable luminescence material from carbon dots (CDs) in boric acid (CD@BA) is reported. At low CDs concentration, the luminescence of CD@BA exhibits a grinding-induced color variable from white to blue. This grinding-induced color variable can be switched to yellow-to-white changing by increasing the CDs concentration in BA. The grinding-induced color-variable luminescence originates from dynamic variation in emission ratio of fluorescence and room temperature phosphorescence, due to the influence of oxygen and water vapor in the air. At high CDs concentration, short-wavelength fluorescence undergoes more severe reabsorption compared to room temperature phosphorescence, leading to grinding-induced color-variable switching from white-to-blue to yellow-to-white. Based on the unique properties of CD@BA powder, the applications of recognizing and visualizing fingerprints on the surfaces of various of materials are demonstrated.

Sine-cosine algorithm (SCA) has found a widespread application in various engineering optimization problems. However, SCA suffers from premature convergence and insufficient exploitation. Cylindricity error evaluation is a typical engineering optimization problem related to the quality of cylindrical parts. A hybrid greedy sine-cosine algorithm with differential evolution (HGSCADE) is developed in this paper to solve optimization problems and evaluate cylindricity error. HGSCADE integrates the SCA with the opposition-based population initialization, the greedy search, the differential evolution (DE), the success history-based parameter adaptation, and the Levy flight-based local search. HGSCADE is tested on the CEC2014 benchmark functions and is employed in cylindricity error evaluation. The results show the superiority of HGSCADE to other state-of-the-art algorithms for the benchmark functions and cylindricity error evaluation.

Full thickness cutaneous wound therapy and regeneration remains a critical challenge in clinical therapeutics. Recent reports have suggested that mesenchymal stem cells exosomes therapy is a promising technology with great potential to efficiently promote tissue regeneration. Multifunctional hydrogel composed of both synthetic materials and natural materials is an effective carrier for exosomes loading. Herein, we constructed a biodegradable, dual-sensitive hydrogel encapsulated human umbilical cord-mesenchymal stem cells (hUCMSCs) derived exosomes to facilitate wound healing and skin regeneration process. The materials characterization, exosomes identification, and in vivo full-thickness cutaneous wound healing effect of the hydrogels were performed and evaluated. The in vivo results demonstrated the exosomes loaded hydrogel had significantly improved wound closure, re-epithelialization rates, collagen deposition in the wound sites. More skin appendages were observed in exosomes loaded hydrogel treated wound, indicating the potential to achieve complete skin regeneration. This study provides a new access for complete cutaneous wound regeneration via a genipin crosslinked dual-sensitive hydrogel loading hUCMSCs derived exosomes.

PEG-interpenetrated dual-sensitive hydrogels that load nano lipid carrier (NLC) were researched and developed for topical drug administration. Natural antioxidant α-lipoic acid (ALA) was selected as our model drug. The α-lipoic acid (ALA) nano lipid carrier was successfully prepared by hot melt emulsification and ultrasonic dispersion method, and the physicochemical properties of the nano lipid carrier were investigated, including morphology, particle distribution, polydispersity coefficient, zeta potential and encapsulation efficiency. Carboxymethyl chitosan and poloxamer 407 contributed to pH- and temperature-sensitive properties in the hydrogel, respectively. Natural non-toxic cross-linking agent genipin reacted with carboxymethyl chitosan to form the hydrogel. Poly ethylene glycol (PEG), a polymer compound with good water solubility and biocompatibility, interpenetrated the hydrogel and influenced the mechanical strength and drug release behaviour. FI-IR test verified the successful synthesis of the hydrogel. The rheological parameters indicated that the mechanical strength of the hydrogel was positively correlated with the amount of PEG, and the in vitro dissolution profiles demonstrated that the increasement of PEG could accelerate the drug release rate. The compatibility of the drug delivery system was verified with cells and mice model. Topical delivery of ALA in solution, NLC and NLC-gel was investigated in-vitro.

The rarity and complexity of histology lead to the low diagnosis rate and high misdiagnosis rate of combined small cell lung cancer (C-SCLC). Nowadays, C-SCLC has no commonly recommended therapeutic regimen, mainly conforming to SCLC treatment. Here, we report a patient initially diagnosed as IIIA “lung squamous cell carcinoma” by a small specimen. Radical resection was achieved after neoadjuvant immunochemotherapy, and the final surgical pathology was C-SCLC containing three different histological components. Moreover, in the literature review, we explored the therapeutic effect of neoadjuvant immunotherapy in C-SCLC, expounded the therapeutic conflicts among heterogeneous components, and analyzed the pathology complexity at the tissue, cell, and molecule levels in-depth, including possible genetic characteristics, origin, and evolution by next-generation sequencing (NGS).

BackgroundAs an emerging therapy with a promising efficacy, immunotherapy has been widely used in the treatment of solid tumors and hematologic malignancies. This clinical study compares the efficacy of tislelizumab, a domestic immune checkpoint inhibitor (ICI), to that of sorafenib when used as a first-line therapeutic option in hepatocellular carcinoma (HCC), and the concurrence of HCC and non-Hodgkin’s lymphoma (NHL) is rare, especially in the treatment of ICIs.Case presentationA 61-year-old patient presenting with primary HCC and indolent B-cell lymphoma had a partial clinical response to tislelizumab for his primary HCC. Besides, we described a phenomenon of pseudo-progression and delayed diagnosis of his lymphoma during a long course of treatment.ConclusionTislelizumab, an immunotherapeutic option with a favorable efficacy and toxicity, can be used to manage double primary tumors. However, studies should aim to elucidate the probable mechanisms of this therapy. Pseudo-progression and separation remission make the treatment of double primary tumors even more challenging, which calls for additional caution in patients undergoing immunotherapy to avoid misdiagnosis and, therefore, begin early appropriate interventions.

Cholangiocarcinoma (CCA) is a refractory cancer with limited treatment options and poorly understood molecular mechanisms underlying tumor development. The most effective treatment is surgical resection; however, patients are highly prone to recurrence. Moreover, considering that most patients are diagnosed in advanced stages, treatment options are restricted to palliative care, which results in poor prognosis. Due to the limited effect of chemotherapy and radiotherapy, targeted therapy is becoming a hot topic in the field of biliary cancer treatment. The fibroblast growth factor/fibroblast growth factor receptor (FGF/FGFR) signaling pathway involves a variety of key biological processes for cell survival, differentiation, and metabolism. Next-generation sequencing data mining has shown that high levels of FGF/FGFR expression are associated with reduced overall survival (OS) in CAA, which indicates that the FGF/FGFR pathway may be an effective target for CAA treatment. This paper reviews the effect of FGF/FGFR signaling on CCA from onset to treatment and highlights the promise of FGF/FGFR signaling pathway inhibitors for targeting CCA.

Astrocytes are the most abundant glial cells in the central nervous system (CNS). As indispensable elements of the neurovascular unit, they are involved in the inflammatory response and disease-associated processes. Alpha-synuclein (α-syn) is released into the extracellular space by neurons and can be internalized by adjacent astrocytes, which activates glial cells to induce neuroinflammation. We were interested in whether astrocyte-mediated neuroinflammation is modulated by intracellular iron status and extracellular α-syn. Our results showed that recombinant α-syn (1 μg/ml and 5 μg/ml) treatment for 24 h did not affect the expression of the iron transporters divalent metal transporter 1 (DMT1) and ferroportin 1 (FPN1), nor those of iron regulatory protein (IRP) 1 or IRP2. Several proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 exhibited up-regulated mRNA levels in 5 μg/ml α-syn-treated astrocytes. TNF-α release was increased, indicating that inflammatory responses were triggered in these cells. Pretreatment with the iron-overload reagent ferric ammonium citrate (FAC, 100 μmol/L) for 24 h had no effects on mRNA levels and release of proinflammatory cytokines. Inflammatory responses triggered by α-syn were not affected by iron overload. The iron chelator desferrioxamine (DFO, 100 μmol/L) exerted suppressive effects on TNF-α mRNA levels, although no change was observed for TNF-α release. Hepcidin mRNA levels were down-regulated significantly in astrocytes co-treated with FAC and α-syn, although independent treatment with either FAC or α-syn did not alter hepcidin levels. In contrast, hepcidin mRNA levels were up-regulated in DFO and α-syn co-treated cells. As expected, ferritin protein levels were up-regulated or down-regulated with FAC or DFO treatment, respectively. Following the up-regulation of ferritin mediated by α-syn, hepcidin-to-ferritin levels were indicative of modulatory effects in α-syn-treated astrocytes with altered iron status. Therefore, we propose that the hepcidin-to-ferritin ratio is indicative of a detrimental response in primary cultured astrocytes experiencing iron and extracellular α-syn.

Abstract Background Cancer initiation genes (CIGs) are genes that can directly promote cell proliferation or induce cancer. There are thousands of published studies identifying various CIGs; however, no systematic collection or description is available. Results To construct a CIG reference for genetic screening, we have collected 177 human genes curated from 1507 PubMed abstracts. To facilitate data queries and browsing, the identified CIGs along with extensive bioinformatic annotations were stored in an online database called CIGene. Initial functional analysis revealed an overlooked role for cell motility in cancer initiation. Subsequent cross-referencing of known tumor suppressor genes and oncogenes against the 177 CIGs identified 96 and 81 CIGs with and without known oncogenic roles, respectively. Successive network analyses of all 177 CIGs determined that the two groups of genes were more likely to link within their group. The distinct molecular functions for these groups were also confirmed with functional studies. While the 96 known oncogenic genes had fundamental roles in gene regulation and signaling, the remaining 81 genes possessed more ancillary functions, such enhancer binding. Further network and mutational analysis of the 96 known oncogenic genes revealed that mutations in these genes were highly prevalent in multiple cancers. By focusing on breast cancer, we found that 32 of the 96 genes with mutations in breast cancers were significantly associated with patient survival. Conclusions As the first literature-based online resource for CIGs, CIGene will serve as a useful gateway for the systematic analysis of cancer initiation. CIGene is freely available to all academic users at http://soft.bioinfo-minzhao.org/cigene/.

A long phosphorescence lifetime is desirable for imaging and detection, however, phosphorescence is often quenched in aqueous environments limiting applications. Here, Li et al. present a strategy for the long-lived phosphorescence of carbon dots in water due to multiple hydrogen-bonding interactions

Spherical Nb-Ti based alloy powder was prepared by the combination of plasma spheroidization and mechanical alloying. Phase constituents, microstructure and surface state of the powder, and pore characteristics of the resulting porous alloy were investigated. The results show that the undissolved W and V in the mechanically alloyed powder is fully alloyed after spheroidization, and single β phase is achieved. Particle size of the spheroidized powder is in the range of 20–110 μm. With the decrease of particle size, a transformation from typical dendrite solidification structure to fine cell microstructure occurs. The surface of the spheroidized powder is coated by a layer of oxides consisting mainly of TiO2 and Nb2O5. Probabilities of sinter-neck formation and particle coalescence increases with increasing sintering temperature. Porous skeleton with relatively homogeneous pore distribution and open pore channel is formed after vacuum sintering at 1700 °C, and the porosity is 32%. The sintering kinetic analysis indicates that grain boundary diffusion is the primary mass transport mechanism during sintering process. Keywords: Powder metallurgy, Nb-Ti based alloy, Porous material, Mechanical alloying, Plasma spheroidizing, Solidification microstructure

Meta-analysis of 2 × 2 tables is common and useful in research topics including analysis of adverse events and survey research data. Fixed-effects inference typically centers on measures of association such as the Cochran-Mantel-Haenszel statistic or Woolf's estimator, but relies on assuming exact homogeneity across studies, which is often unrealistic. By showing that estimators of several widely-used methods have meaningful estimands even in the presence of heterogeneity, we derive improved confidence intervals for them under heterogeneity. These improvements over current methods are illustrated by simulation, and we also study which factors affect the coverage levels. We find that our confidence intervals provide coverage closer to the nominal level when heterogeneity is present, in both small and large-sample settings. The conventional confidence intervals derived under homogeneity are often conservative, though anti-conservative inferences occur in some scenarios. We also apply the proposed methods to a meta-analysis of 19 randomized clinical trials on the effect of sclerotherapy in preventing first bleeding for patients with cirrhosis and esophagogastric varices. Our methods provide a more interpretable approach to meta-analyzing binary data and more accuracy in characterizing the uncertainty of the estimators.

Abstract The single transmitter and multiple receivers (STMR) mobile radar system is a special distributed radar system, which has stronger detection and survival capabilities. However, the high‐speed movement of the radar platforms easily produce the across‐range cell migration (RCM) of radar echo signal, which cause envelope shift effects within the coherent processing interval. Here, a motion compensation method for the STMR mobile radar system in the sea environment, to solve the problem of RCM is proposed. First, the target points and clutter points with the same Doppler velocity are obtained by the radon Fourier transform method. Second, using the range/Doppler difference between clutter and target under multi‐radar views, the target and clutter points are separated by the spatial range mapping. The simulation results show that the method can effectively improve the coherent accumulation effect of the target in the sea environment with low signal‐to‐clutter ratio (SCR).

ABSTRACT: Rising temperatures and intensified agricultural practices have heightened heat stress (HS)-related challenges in poultry farming, notably heat-induced sudden death in chickens. Wenchang chickens, recognized for their heat resistance, have emerged as the potential candidates for improving the economic efficiency of poultry farming. The adrenal gland plays a crucial role in preventing HS-induced heart failure sudden death by secreting hormones. However, little is known about the damage to and resilience of Wenchang chicken adrenal glands during HS. In this study, 34 healthy Wenchang chickens with similar weights were selected for formal experimentation, with 10 as the control group (Con). Following a single exposure to acute HS of 42 ± 1°C and 65% relative humidity for 5 h, 15 deceased individuals formed the HS death (HSD) group, and 9 survived comprised the HS survival (HSS) group. ELISA revealed significant higher (P < 0.05) levels of COR and NE in the HSS and the lowest levels of CORT and EPI in the HSD. Histopathological analysis indicated major degeneration in HSS cortical and chromaffin cells and extensive cell necrosis (nuclear pyknosis) in HSD. Proteomic analysis identified 572 DEPs in HSD vs. Con and 191 DEPs in HSS vs. Con. Bioinformatics highlighted ER protein processing, especially ERAD as a key pathway for heat stress resistance (HSR) in the adrenal gland, with HSPH1, DNAJA1, HSP90AA1, HSPA8 and HERPUD1 identified as regulating key molecules. Western blotting validated significantly higher (P < 0.01) protein levels in both HSS and HSD compared to the Con. Immunohistochemical staining showed increased cytoplasmic HSPH1-positive signal intensity under HS and enhanced HSP90AA1 nuclear signals, strongest in HSS. In summary, HS induces pathological damage in Wenchang chicken adrenal glands, affecting hormone secretion, and various heat shock proteins play crucial roles in cellular resistance. These results elucidate the biological basis of HSR in Wenchang chickens from the perspective of the adrenal gland and provide necessary research foundations for enhancing economic performance of various broilers in high-heat environments and screening drugs for HS treatment.

The outstanding performance of aluminized explosives is attributed to the substantial energy released through aluminum (Al) reactions during post-detonation flow. However, the influences of Al powder size on the explosion power of aluminized explosives sometimes vary significantly across different time scales, which may suggest potential differences in Al reaction processes. To investigate the size-dependent reaction behavior of Al powders at different time scales, a novel experimental apparatus was employed to measure the velocity of a rod propelled by the detonation products of RDX/Al explosives (with Al powder sizes of 1.9 µm or 47.1 µm)1 at ∼1 ms, and the results were compared to those obtained from previous tube tests at around 30 µs. The experimental findings reveal that the impact of Al powder size on the metal-driven capability of aluminized explosives is not substantial at either 1 ms or 30 µs. Given the inadequacy of the phenomenological equation of state for studying the Al reaction due to its inability to ensure the uniqueness of the reaction process, we investigated the tburn∝dAln law using the Gurney energy method, where dAl and tburn denote the powder size and combustion time of Al powders, respectively. The values of n (0.031 and 0.038) were examined for the first time in post-detonation flow, which are significantly smaller than those observed in quasi-static flow. These results substantiate that the weak powder size effect on Al reaction is likely a prevalent phenomenon for micron-sized Al powders in post-detonation flow, attributable to the high pressure and high velocity characteristic of such flows.

By combination of the transient Raman spectroscopic measurement and the density functional theoretical calculations, the structural evolution and stability of TATB under shock compression was investigated. Due to the improvement in synchronization control between two-stage light gas gun and the transient Raman spectra acquisition, as well as the sample preparation, the Raman peak of the N–O mode of TATB was firstly observed under shock pressure up to 13.6 GPa, noticeably higher than the upper limit of 8.5 GPa reported in available literatures. By taking into account of the continuous shift of the main peak and other observed Raman peaks, we did not distinguish any structural transition or any new species. Moreover, both the present Raman spectra and the time-resolved radiation of TATB during shock loading showed that TATB exhibits higher chemical stability than previous declaration. To reveal the detailed structural response and evolution of TATB under compression, the density functional theoretical calculations were conducted, and it was found that the pressure make N–O bond lengths shorter, nitro bond angles larger, and intermolecular and intra-molecular hydrogen bond interactions enhanced. The observed red shift of Raman peak was ascribed to the abnormal enhancement of H-bound effect on the scissor vibration mode of the nitro group.

As an energetic material of great interest, the work capacity of dihydroxylammonium 5,5′-bistetrazole-1,1′-diolate (TKX-50) has been questioned recently. Although some research groups have explored the reasons for the low working ability of TKX-50, the plane impact experiment on powdered TKX-50 is obviously closer to the practical application, and the conclusions based on this are more guiding. Hence, we performed shock Hugoniot measurements of powdered TKX-50 between 5.65 and 16.29 GPa. The plane impact experiments of powdered TKX-50 were carried out and the shocked Raman spectra were collected. By Raman spectroscopy analysis, a new peak of powdered TKX-50 was found between 19.47 GPa and 24.96 GPa, which may be caused by decomposition/phase transition and was related with the low work capacity.

IntroductionUltrasound is instrumental in the early detection of thyroid nodules, which is crucial for appropriate management and favorable outcomes. However, there is a lack of clinical guidelines for the judicious use of thyroid ultrasonography in routine screening. Machine learning (ML) has been increasingly used on big data to predict clinical outcomes. This study aims to leverage the ML approach in assessing the risk of thyroid nodules based on common clinical features.MethodsData were sourced from a Chinese cohort undergoing routine physical examinations including thyroid ultrasonography between 2013 and 2023. Models were established to predict the 3-year risk of thyroid nodules based on patients’ baseline characteristics and laboratory tests. Four ML algorithms, including logistic regression, random forest, extreme gradient boosting, and light gradient boosting machine, were trained and tested using fivefold cross-validation. The importance of each feature was measured by the permutation score. A nomogram was established to facilitate risk assessment in the clinical settings.ResultsThe final dataset comprised 4,386 eligible subjects. Thyroid nodules were detected in 54.8% (n=2,404) individuals within the 3-year observation period. All ML models significantly outperformed the baseline regression model, successfully predicting the occurrence of thyroid nodules in approximately two-thirds of individuals. Age, high-density lipoprotein, fasting blood glucose and creatinine levels exhibited the highest impact on the outcome in these models. The nomogram showed consistency and validity, providing greater net benefits for clinical decision-making than other strategies.ConclusionThis study demonstrates the viability of an ML-based approach in predicting the occurrence of thyroid nodules. The findings highlight the potential of ML models in identifying high-risk individuals for personalized screening, thereby guiding the judicious use of ultrasound in this context.

The annual co-circulation of two influenza A subtypes, H1N1 and H3N2, viruses in humans poses significant public health threats worldwide. However, the continuous antigenic drift and shift of influenza viruses limited the effectiveness of current seasonal influenza vaccines, necessitating the development of new vaccines against both seasonal and pandemic viruses. One potential solution to this challenge is to improve inactivated vaccines by including multiple T-cell epitopes. In this study, we designed stabilized trimeric recombinant mosaic HA proteins named HAm, which contain the most potential HA T-cell epitopes of seasonal influenza A virus. We further evaluated the antigenicity, hemagglutinin activity, and structural integrity of HAm and compared its immunogenicity and efficacy to a commercial quadrivalent inactivated influenza vaccine (QIV) in mice. Our results demonstrated that the HAm vaccine was able to induce broadly cross-reactive antibodies and T-cell responses against homologous, heterologous, and heterosubtypic influenza-naive mice. Additionally, the HAm antigens outperformed QIV vaccine antigens by eliciting protective antibodies against panels of antigenically drifted influenza vaccine strains from 2009 to 2024 and protecting against ancestral viruses’ lethal challenge. These results suggest that the HAm vaccine is a promising potential candidate for future universal seasonal and pandemic influenza vaccine development.

Abstract The second most common male cancer is prostate cancer (PCa), which has a high tendency for bone metastasis. Long non-coding RNAs, including TMPO-AS1, play a crucial role in PCa progression. However, TMPO-AS1’s function in PCa bone metastasis (BM) and its underlying molecular mechanisms are unclear. Herein, we found that the long transcript of TMPO-AS1 (TMPO-AS1 L ) was upregulated in PCa tissues with bone metastasis, and overexpression of TMPO-AS1 L correlated with advanced clinicopathological features and reduced BM-free survival in patients with PCa. Upregulated TMPO-AS1 L promoted, whereas downregulated TMPO-AS1 L inhibited, the PCa cell bone metastatic capacity in vitro and in vivo. Mechanistically, TMPO-AS1 L was demonstrated to act as a scaffold, that strengthened the interaction of casein kinase 2 alpha 1 (CSNK2A1) and DEAD-box helicase 3 X-linked (DDX3X), and activated the Wnt/β-catenin signaling pathway, thus promoting BM of PCa. Moreover, upregulation of TMPO-AS1 L in PCa resulted from transcription elongation modulated by general transcription factor IIF subunit 2 (GTF2F2). Collectively, our study provides critical insights into the role of TMPO-AS1 L in PCa BM via Wnt/β-catenin signaling, identifying TMPO-AS1 L as a candidate marker of PCa bone metastasis prognosis and therapeutic target.

Abstract Background Diabetes is associated with high morbidity, mortality and quality-of-life impairment in patients. In China, the number of people suffering from diabetes ranks first in the world. Gansu Province is located in northwest China and is an economically underdeveloped region of China. By analyzing the level of health service utilization of people with diabetes in Gansu Province, the degree of equity in health service utilization and its influencing factors were studied to provide scientific data to support the promotion of health equity for people with diabetes and the introduction of relevant policies by relevant authorities. Methods A sample of 282 people with diabetes who were 15 years old and above was chosen by multi-stage stratified sampling method. A structured questionnaire survey was conducted via face-to-face interviews. Random forest and logistic regression analysis were used to demonstrate the effects of the explanatory variables on health seeking behaviors from predisposing, enabling and need variables. The concentration index was used to indicate the equity of health service utilization across households of different economic levels. Results The outpatient rate for the diabetic population surveyed was 92.91%, with 99.87% of urban patients, higher than the 90.39% of rural patients. The average number of hospital days per person was 3.18 days, with 5.03 days per person in urban areas, which was higher than the 2.51 days per person in rural areas. The study showed that the factors most likely to influence patients to seek outpatient services were frequency of taking diabetic medication, whether or not they were contracted to a household doctor, and living environment; the top three factors most likely to influence patients with diabetes to seek inpatient services were number of non-communicable chronic disease, self-assessment of health status, medical insurance. The concentration index for outpatient service utilization and inpatient service utilization were − 0.241 and 0.107, respectively, indicating that outpatient services were concentrated on patients at lower income levels and patients at higher income levels tended to favor inpatient services. Conclusion This study found that the low level of health care resources available to people with diabetes, whose health status is suboptimal, makes it difficult to meet their health needs. Patients' health conditions, comorbidities of people with diabetes, and the level of protection were still important factors that hindered the use of health services. It is necessary to promote the rational use of health services by diabetic patients and further improve the corresponding policies to achieve the goal of chronic disease prevention and control in “Health China 2030”.

ABSTRACT: Heat stress (HS) can result in sudden death and is one of the most stressful and costly events in chicken. Currently, biomarkers used clinically to detect heat stress state in chickens are not optimal, especially for living ones. Analysis of changes in serum proteins of heat-stressed chickens can help to identify some novel convenient biomarkers for this. Twenty-four chickens were exposed to HS at 42°C ± 1°C with a relative humidity of 65% for continuous 5 h in a single day, and 10 birds were used as controls (Con). During HS, 15 dead chickens were categorized as heat stress death group (HSD), and 9 surviving ones served as heat stress survivor group (HSS). Label-free quantitative proteomics (LFQP) was used to analyze differentially expressed proteins (DEPs) in serum of tested animals. Candidate proteins associated with HS were validated by enzyme-linked immunosorbent assay (ELISA). Diagnostic value of candidate biomarkers was assessed using receiver operating characteristic (ROC) curve analysis. Source of the selected proteins was analyzed in liver tissues with immunohistochemistry and in cell culture supernatant of primary chicken hepatocytes (PCH) using ELISA. In this study, compared to Con, LFQP identified 123 and 53 significantly different serum proteins in HSD and HSS, respectively. Bioinformatics analysis showed that XDH, POSTN, and HSP90 were potential HS biomarkers in tested chickens, which was similar with results from serum ELISAs and immunohistochemistry in liver tissues. The ROC values of 0.793, 0.752, and 0.779 for XDH, POSTN, and HSP90, respectively, permitted the distinction of heat-stressed chickens from the control. Levels of 3 proteins above in the cell culture supernatant of PCH showed an increasing trend as HS time increased. Therefore, considering that mean concentration of POSTN in serum was higher than that of HSP90, XDH, and POSTN may be optimal biomarkers in serum for detecting HS level in chickens, and mainly secreted from hepatocytes. The former indicates that heat-stressed chickens are in a damaged state, and the latter implies that chickens can repair heat stress damage.

Numerous studies have reported a correlation between gut microbiota and influenza A virus (IAV) infection and disease severity. However, the causal relationship between these factors remains inadequately explored. This investigation aimed to assess the influence of gut microbiota on susceptibility to human infection with H7N9 avian IAV and the severity of influenza A (H1N1)pdm09 infection. A two-sample Mendelian randomization analysis was conducted, integrating our in-house genome-wide association study (GWAS) on H7N9 susceptibility and H1N1pdm09 severity with a metagenomics GWAS dataset from a Chinese population. Twelve and fifteen gut microbiotas were causally associated with H7N9 susceptibility or H1N1pdm09 severity, separately. Notably, Clostridium hylemonae and Faecalibacterium prausnitzii were negative associated with H7N9 susceptibility and H1N1pdm09 severity, respectively. Moreover, Streptococcus peroris and Streptococcus sanguinis were associated with H7N9 susceptibility, while Streptococcus parasanguini and Streptococcus suis were correlated with H1N1pdm09 severity. These results provide novel insights into the interplay between gut microbiota and IAV pathogenesis as well as new clues for mechanism research regarding therapeutic interventions or IAV infections. Future studies should concentrate on clarifying the regulatory mechanisms of gut microbiota and developing efficacious approaches to reduce the incidence of IAV infections, which could improve strategy for preventing and treating IAV infection worldwide.

Ethylenediamine bisborane (EDAB), as a hydrogen storage material, is one of the most promising possible candidates. This work reports the effects of pressure on the structural, mechanical, electronic, and vibrational behaviors of EDAB using density functional theory calculations. The predicted lattice parameters, bulk modulus B0 and its first pressure derivative B′ are in accord with available experimental data. From the unit-cell constants as a function of pressure, crystal EDAB is found to present an anisotropic compressibility. The calculated elastic properties show that the ambient phase EDAB is mechanical unstable at 3 GPa. Furthermore, the discontinuous behavior was found in the pressure dependence of crystal and electronic structure, suggesting a structural transformation occurred around 3 GPa. Finally, vibrational spectra are reported together with their infrared active modes assignment. The NH and BH stretching modes soften under compression, indicating the strengthening of hydrogen bonding, which leads to the occurrence of pressure-induced structural transformation.

Abstract Background Aimed to corroborate students' and faculty's experiences with e-learning during the current pandemic. Methods A cross-sectional study was conducted from February to June 2020. Seven surveys were distributed electronically to all undergraduate students and the faculty (4 to students and 3 to teachers) at the Southern Medical University (China). Descriptive statistics and t-tests were used to analyze the data. Statistical significance was set at p

Despite many studies on the immune characteristics of Coronavirus disease 2019 (COVID-19) patients in the progression stage, a detailed understanding of pertinent immune cells in recovered patients is lacking. We performed single-cell RNA sequencing on samples from recovered COVID-19 patients and healthy controls. We created a comprehensive immune landscape with more than 260,000 peripheral blood mononuclear cells (PBMCs) from 41 samples by integrating our dataset with previously reported datasets, which included samples collected between 27 and 47 days after symptom onset. According to our large-scale single-cell analysis, recovered patients, who had severe symptoms (severe/critical recovered), still exhibited peripheral immune disorders 1–2 months after symptom onset. Specifically, in these severe/critical recovered patients, human leukocyte antigen (HLA) class II and antigen processing pathways were downregulated in both CD14 monocytes and dendritic cells compared to healthy controls, while the proportion of CD14 monocytes increased. These may lead to the downregulation of T-cell differentiation pathways in memory T cells. However, in the mild/moderate recovered patients, the proportion of plasmacytoid dendritic cells increased compared to healthy controls, accompanied by the upregulation of HLA-DRA and HLA-DRB1 in both CD14 monocytes and dendritic cells. In addition, T-cell differentiation regulation and memory T cell–related genes FOS, JUN, CD69, CXCR4, and CD83 were upregulated in the mild/moderate recovered patients. Further, the immunoglobulin heavy chain V3-21 (IGHV3-21) gene segment was preferred in B-cell immune repertoires in severe/critical recovered patients. Collectively, we provide a large-scale single-cell atlas of the peripheral immune response in recovered COVID-19 patients.

Wild aquatic birds are the primary natural reservoir of influenza A viruses (IAVs), although a small number of viruses can spill over to mammals and circulate. The focus of IAV infection in mammals was largely limited to humans and swine variants, until the emergence of H3N2 canine influenza viruses (CIVs), which provides new perspective for interspecies transmission of the virus. In this study, we captured 54 canine-adaptive signatures in H3N2 CIVs through entropy computation, which were largely concentrated in the interaction region of polymerase proteins on ribonucleoprotein complex. The receiver operating characteristic curves of these sites showed >95% accuracy in distinguishing between the hosts. Nine of the 54 canine-adaptive signatures were shared in avian–human/equine or equine–canine (PB2-82; PB1-361; PA-277; HA-81, 111, 172, 196, 222, 489), suggesting their involvement in canine adaptation. Furthermore, we found that IAVs can establish persistent transmission in lower mammals with greater ease compared to higher mammals, and 25 common adaptation signatures of H3 IAVs were observed in diverse avian–mammals comparison. There were few human-like residues in H3N2 CIVs, which suggested a low risk of human infection. Our study highlights the necessity of identifying and monitoring the emerging adaptive mutations in companion animals by enhanced surveillance and provides a basis for mammal adaptation of avian influenza viruses.