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Valleytronic devices employ the electronic valley degree of freedom to realize potential low-power electronic applications. Here, the authors utilize a topological semiconductor to engineer valley polarization transistors with long lifetimes and demonstrate low-power neuromorphic functionality at room temperature.

Strong, electroactive and ultrafine conducting polymer fibres are prepared at the large scale by a modified wet spinning strategy. The obtained ultrafine polyaniline fibres are qualified to build tactile organic electrochemical transistors.

Autophagy is a highly conserved self-degradation process that involves the degradation and recycling of cellular components and organelles. Although the involvement of autophagy in metabolic changes during fruit ripening has been preliminarily demonstrated, the variations in autophagic flux and specific functional roles in tomato fruit ripening remain to be elucidated. In this study, we analyzed the variations in autophagic flux during tomato fruit ripening. The results revealed differential expression of the SlATG8 family members during tomato fruit ripening. Transmission electron microscopy observations and dansylcadaverine (MDC) staining confirmed the presence of autophagy at the cellular level in tomato fruits. Furthermore, the overexpression of SlATG8f induced the formation of autophagosomes, increased autophagic flux within tomato fruits, and effectively enhanced the expression of ATG8 proteins during the color-transition phase of fruit ripening, thus promoting tomato fruit maturation. SlATG8f overexpression also led to the accumulation of vitamin C (VC) and soluble solids while reducing acidity in the fruit. Collectively, our findings highlight the pivotal role of SlATG8f in enhancing tomato fruit ripening, providing insights into the mechanistic involvement of autophagy in this process. This research contributes to a better understanding of the key factors that regulate tomato fruit quality and offers a theoretical basis for tomato variety improvement.

The post-translational import of nuclear-encoded chloroplast preproteins is critical for chloroplast biogenesis, and the Toc159 family of proteins is the receptor for this process. Our previous work identified and analyzed the Toc GTPase in tomato; however, the tomato-specific transport substrate for Toc159 is still unknown, which limits the study of the function of the TOC receptor in tomato. In this study, we expand the number of preprotein substrates of slToc159 receptor family members using slToc159-1 and slToc159-2 as bait via a split-ubiquitin yeast two-hybrid membrane system. Forty-one specific substrates were identified in tomato for the first time. Using slToc159-1GM and slToc159-2GM as bait, we compared the affinity of the two bait proteins, with and without the A domain, to the precursor protein, which suggested that the A domain endowed the proproteins with subclass specificity. The presence of the A domain enhanced the interaction intensity of slToc159-1 with the photosynthetic preprotein but decreased the interaction intensity of slToc159-2 with the photosynthetic preprotein. Similarly, the presence of the A domain also altered the affinity of slToc159 to non-photosynthetic preproteins. Bimolecular fluorescence complementation (BiFC) analysis showed that A domain had the ability to recognize the preprotein, and the interaction occurred in the chloroplast. Further, the localization of the A domain in Arabidopsis protoplasts showed that the A domain did not contain chloroplast membrane targeting signals. Our data demonstrate the importance of a highly non-conserved A domain, which endows the slToc159 receptor with specificity for different protein types. However, the domain containing the information on targeting the chloroplast needs further study.

The translocon at the outer envelope membrane of chloroplasts (Toc) mediates the recognition and initial import into the organelle of thousands of nucleus-encoded proteins. These proteins are translated in the cytosol as precursor proteins with cleavable amino-terminal targeting sequences called transit peptides. The majority of the known Toc components that mediate chloroplast protein import were originally identified in pea, and more recently have been studied most extensively in Arabidopsis. With the completion of the tomato genome sequencing project, it is now possible to identify putative homologues of the chloroplast import components in tomato. In the work reported here, the Toc GTPase cDNAs from tomato were identified, cloned and analyzed. The analysis revealed that there are four Toc159 homologues (slToc159-1, -2, -3 and -4) and two Toc34 homologues (slToc34-1 and -2) in tomato, and it was shown that tomato Toc159 and Toc34 homologues share high sequence similarity with the comparable import apparatus components from Arabidopsis and pea. Thus, tomato is a valid model for further study of this system. The expression level of Toc complex components was also investigated in different tissues during tomato development. The two tomato Toc34 homologues are expressed at higher levels in non-photosynthetic tissues, whereas, the expression of two tomato Toc159 homologues, slToc159-1 and slToc159-4, were higher in photosynthetic tissues, and the expression patterns of slToc159-2 was not significantly different in photosynthetic and non-photosynthetic tissues, and slToc159-3 expression was limited to a few select tissues.

Due to the high dispersion of solid powder, it is very easy to form a powder/gas hybrid system, which greatly increases the probability and severity of explosion accidents. The researchers both domestically and internationally have conducted extensive research on the hybrids explosion systems. This paper reviews the combustion characteristics, explosion mechanisms, and explosion prevention experiments of hybrids. Current research results on explosion prevention technology are organized, and the current challenges in experimental studies of hybrids explosions are summarized, providing references for future experimental studies.

Abstract Background Global warming-induced environmental stresses have diverse effects on gene expression and regulation in the life processes of various aquatic organisms. N6 adenylate methylation (m6A) modifications are known to influence mRNA transcription, localization, translation, stability, splicing, and nuclear export, which are pivotal in mediating stress responses. Apostichopus japonicus is a significant species in aquaculture and a representative of benthic organisms in ecosystems, thus there is a growing need for research on its heat stress mechanism. Results In this study, m6A-modified whole transcriptome profiles of the respiratory tree tissues of A. japonicus in the control (T18) and high-temperature stress (T32) groups were obtained using MeRIP-seq technology. The results showed that 7,211 common m6A peaks, and 9,459 genes containing common m6A were identified in three replicates T18 and T32 groups. The m6A peaks were found to be highly enriched in the 3’ untranslated region, and the common sequence of the m6A peak was also enriched, which was shown as RRACH (R = G or A; H = A, C, or U). A total of 1,200 peaks were identified as significantly differentially enriched in the T32 group compared with the T18 group. Among them, 245 peaks were upregulated and 955 were downregulated, which indicated that high temperature stress significantly altered the methylation pattern of m6A, and there were more demethylation sites in the T32 group. Conjoint analysis of the m6A methylation modification and the transcript expression level (the MeRIP-seq and RNA-seq data) showed co-differentiated 395 genes were identified, which were subsequently divided into four groups with a predominant pattern that more genes with decreased m6A modification and up-regulated expression, including HSP70IV, EIF2AK1, etc. GO enrichment and KEGG analyses of differential m6A peak related genes and co-differentiated genes showed the genes were significantly associated with transcription process and pathways such as protein processing in the endoplasmic reticulum, Wnt signaling pathway, and mTOR signaling pathway, etc. Conclusion The comparisons of m6A modification patterns and conjoint analyses of m6A modification and gene expression profiles suggest that m6A modification was involved in the regulation of heat stress-responsive genes and important functional pathways in A. japonicus in response to high-temperature stress. The study will contribute to elucidate the regulatory mechanism of m6A modification in the response of A. japonicus to environmental stress, as well as the conservation and utilization of sea cucumber resources in the context of environmental changes.

Abstract The expression and biological function of junctional adhesion molecule-like protein (JAML) in colorectal cancer (CRC) remain unclear. Paraffin tissue samples from 50 cases of CRC were collected to determine the expression of JAML. JAML was overexpressed or knock-down in CRC cells to evaluated the proliferation, migration and invasion in vitro and in vivo. Western-blot and others were applied to explore the mechanisms. The study showed that JAML was highly expressed within cancer tissues in 50% (25/50) of patients with CRC, and was correlated with higher TNM stage (p

Abstract The pathogenesis of doxorubicin-induced cardiomyopathy remains unclear. This study was carried out to test our hypothesis that ADAM17 aggravates cardiomyocyte apoptosis induced by doxorubicin and inhibition of ADAM17 may ameliorate doxorubicin-induced cardiomyopathy. C57BL/6J mice were intraperitoneally injected with a cumulative dose of doxorubicin to induce cardiomyopathy. Cardiomyocyte-specific ADAM17-knockout (A17α-MHCKO) and ADAM17-overexpressing (AAV9-oeA17) mice were generated. In addition, RNA sequencing of the heart tissues in different mouse groups and in vitro experiments in neonatal rat cardiomyocytes (NRCMs) receiving different treatment were performed. Mouse tumor models were constructed in A17fl/fl and A17α-MHCKO mice. In addition, cardiomyocyte-specific TRAF3-knockdown and TRAF3-overexpressing mice were generated. ADAM17 expression and activity were markedly upregulated in doxorubicin-treated mouse hearts and NRCMs. A17α-MHCKO mice showed less cardiomyocyte apoptosis induced by doxorubicin than A17fl/fl mice, and cardiomyocyte ADAM17 deficiency did not affect the anti-tumor effect of doxorubicin. In contrast, AAV9-oeA17 mice exhibited markedly aggravated cardiomyocyte apoptosis relative to AAV9-oeNC mice after doxorubicin treatment. Mechanistically, doxorubicin enhanced the expression of transcription factor C/EBPβ, leading to increased expression and activity of ADAM17 in cardiomyocyte, which enhanced TNF-α shedding and upregulated the expression of TRAF3. Increased TRAF3 promoted TAK1 autophosphorylation, resulting in activated MAPKs pathway and cardiomyocyte apoptosis. ADAM17 acted as a positive regulator of cardiomyocyte apoptosis and cardiac remodeling and dysfunction induced by doxorubicin by upregulating TRAF3/TAK1/MAPKs signaling. Thus, targeting ADAM17/TRAF3/TAK1/MAPKs signaling holds a promising potential for treating doxorubicin-induced cardiotoxicity.

Abstract Background Several abdominal obesity indices including waist circumference (WC), waist–hip ratio (WHR), visceral adiposity index (VAI), lipid accumulation product (LAP), and Chinese visceral adiposity index (CVAI) were considered effective and useful predictive markers for cardiovascular disease (CVD) in general populations or diabetic populations. However, studies investigating the associations between these indices among postmenopausal women are limited. Our study aimed to investigate the associations of the five indices with incident CVD and compare the predictive performance of CVAI with other abdominal obesity indices among postmenopausal women. Methods A total of 1252 postmenopausal women without CVD at baseline were analyzed in our investigation based on a 10-year follow-up prospective cohort study. Link of each abdominal obesity index with CVD were assessed by the Cox regression analysis and the Kaplan–Meier curve. The receiver operating characteristic (ROC) curves were drawn to compare the predictive ability for CVD. Results During the median follow-up of 120.53 months, 121 participants newly developed CVD. Compared to quartile 1 of LAP and CVAI, quartile 4 had increased risk to develop CVD after fully adjusted among postmenopausal women. When WC, VAI and CVAI considered as continuous variables, significant increased hazard ratios (HRs) for developing CVD were observed. The areas under the curve (AUC) of CVAI (0.632) was greatly higher than other indices (WC: 0.580, WHR: 0.538, LAP: 0.573, VAI: 0.540 respectively). Conclusions This study suggested that the abdominal obesity indices were associated with the risk of CVD excluded WHR and highlighted that CVAI might be the most valuable abdominal obesity indicator for identifying the high risk of CVD in Chinese postmenopausal women.

Introduction To investigate the efficacy and safety of Cutegel® MAX (Cutegel) in the correction of moderate-to-severe nasolabial folds (NLFS) compared to Restylane® (Restylane, control).Methods This study was a 52-week, multicenter, randomized, double-blinded, active-controlled clinical trial. Qualified participants with moderate-to-severe NLFs were randomly assigned in a 1:1 ratio to receive Cutegel or Restylane. For the primary efficacy endpoint, the response rate was defined as the percentage of subjects exhibiting an improvement of at least one-point based on blinded evaluation of Wrinkle Severity Rating Scale (WSRS) at 24 weeks after injection. Other secondary efficacy endpoints and treatment-emergent adverse events (TEAEs) were assessed.Results Of 340 subjects randomized, 317 completed the week 52 visit. In the per protocol set (PPS), the blinded evaluator-assessed response rates at week 24 were 81.17% for Cutegel versus 77.56% for Restylane (p = 0.327). The between-group treatment differences in response rates were 3.60% [95% confidence interval (CI) = (−5.39%, 12.60%)], which demonstrated the noninferiority of Cutegel. Other secondary efficacy endpoints supported this. No significant differences were observed in the occurrence of adverse events between the two groups.Conclusion Similar to Restylane, Cutegel was effective and well tolerated in correcting moderate-to-severe NLFs among the Chinese population.

One of the major challenges in the aquaculture of marine organisms is the susceptibility to pathogens. Immune cells defend bacterial invasion by recognizing pathogen-associated molecular patterns (PAMPs) such as Lipopolysaccharides (LPS) in Gram-negative bacteria. The white body are key organs for immune response and hematopoiesis, and play an important role in understanding the antimicrobial biological response in gold-ringed octopus (Amphioctopus fangsiao). In the present research, transcriptome sequencing and bioinformatics analysis were conducted on A. fangsiao white body tissue after 6 h and 24 h of LPS stimulation. The results showed 2,029 and 73 differentially expressed genes (DEGs) at the 6- and 24-hour time points, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were beneficial in determining immune-related terms and signaling pathways. Subsequently, a protein-protein interaction (PPI) network was constructed and 20 hub genes, such as AKT3, MAPK14, and PIK3CA, were identified. These genes are involved in a variety of signaling pathways, including the Hippo signaling pathway, chemokine signaling pathway, and leukocyte trans endothelial migration. Using qRT-PCR, the accuracy of the 20 hub genes was verified. The present study provides a substantial theoretical foundation for the research on A. fangsiao white body immunity, enhancing the current understanding of cephalopods' innate immunity.

Apostichopus japonicus (A. japonicus) is known as one of the most popular varieties in aquaculture due to its rich nourishment and potential medicinal value. In recent years, with the abnormal change of marine environment and global climate, new challenges are arising continually in the culture process of A. japonicus. Intestinal flora plays an important role in host health and growth, and a lot of studies confirmed the close relationship between the composition change of intestinal flora and the growth of sea cucumbers. In this study, polypeptidin belonging to bacteriocins, was as an additive ingredient in sea cucumber feed. The growth of A. japonicus increased significantly after polypeptidin feeding, and the growth rate reached the highest with 1 % polypeptidin especially. Subsequently 16 S rRNA of gut microbiota from 1 % polypeptidin group was sequenced and analyzed for richness and diversity index, but the results showed that polypeptidin supplement did not markedly change the diversity and main composition of gut microbiota compared to the control. So the further analyze was performed by dependent t-test for paired samples, and found that the abundance of only a few of species at the class level changed significantly, including Alphaproteobacteria, Desulfotomaculia and Chlamydiae, but many species at the genus level changed significantly. Some important metabolic pathways were identified through function prediction, like TCA cycle, streptomycin biosynthesis and phenylalanine metabolism. At this basis, the analysis combined with the genuses and the metabolic pathways demonstrated that polypeptidin might regulate the richness of some bacteria, which could be involved in enzyme degradation, antibacterial substances secreting or underlying pathogenic tendency of gut microbiota ecosystem. These fine-tunings instead of main community structure change were probably more beneficial to the intestinal flora health, and finally contributed to the growth of A. japonicus. Thus, polypeptidin serves as a mild, non-stimulating feed supplement for A. japonicus, and has good prospects for application.

InTe single crystals have demonstrated great promise in the field of thermoelectric materials, particularly when oriented along the [110] direction. This specific crystal orientation exhibits higher electronic conductivity and lower thermal conductivity compared to other orientations of InTe. Through first-principles calculations, we identified the anisotropic valence band and phonon dispersion as the underlying factors. Moreover, reducing the density of In+ vacancies in InTe was found to lower the band effective mass and modulate carrier scattering, enhancing the material quality factor (B). To explore these findings, we systematically grew InTe single crystals, achieving exceptional thermoelectric performance. A record-breaking power factor of 12.0 μW·cm−1·K−2 and a dimensionless figure of merit (zT) of 0.5 at room temperature were obtained. Notably, InTe crystals oriented along [110] with low In+ vacancy density exhibited the highest average zT of 0.63 among InTe-based thermoelectric materials within the 300–473 K temperature range. Furthermore, we introduced an effective method of reducing In+ vacancies through Indium vapor annealing, resulting in the highest reported carrier mobility of 182 cm2·V−1·s−1 for InTe. Our study highlights the potential for improving InTe's thermoelectric performance near room temperature through vacancy modulation and crystal orientation.

Highlights We present a method that utilizes ionic liquid-enhanced nanomaterial assembly to fabricate highly stable and large-area MXene-silver nanowire electrodes with ordered layered structures. This approach emphasizes the use of hydrophobic and nonvolatile ionic liquids, which form stable interfaces with water by reducing interface energy, preventing the sedimentation loss of nanomaterials during assembly. The prepared electrodes not only exhibit excellent optoelectronic properties (9.4 Ω sq−1 sheet resistance and 93% transmittance), but also have exceptional antioxidant capacity.

Abstract HLX01 (HanliKang®) is a rituximab biosimilar that showed bioequivalence to reference rituximab in untreated CD20-positive diffuse large B-cell lymphoma (DLBCL) in the phase 3 HLX01-NHL03 study. Here, we report the 5-year follow-up results from the open-label extension part. Patients were randomised to either rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or HLX01 plus CHOP (H-CHOP) every 21 days for up to six cycles. The primary efficacy endpoint was overall survival (OS), and secondary efficacy endpoint was progression-free survival (PFS). Of the 407 patients enrolled in HLX01-NHL03, 316 patients (H-CHOP = 157; R-CHOP = 159) were included in the 5-year follow-up for a median duration of 65.1 (range, 2.2–76.5) months. 96.5% of the patients had an International Prognostic Index (IPI) of 1 or 2, and 17.7% had bone marrow involvement. The 5-year OS rates were 81.0% (95% CI: 74.9–87.5%) and 75.4% (95% CI: 68.9–82.6%)( HR: 0.75, 95% CI 0.47–1.20; p = 0.23) while 5-year PFS rates were 77.7% (95% CI: 71.4–84.6%) and 73.0% (95% CI: 66.3–80.3%) (HR: 0.84, 95% CI 0.54–1.30; p = 0.43) in the H-CHOP and R-CHOP groups, respectively. Treatment outcomes did not differ between groups regardless of IPI score and were consistent with the primary analysis. H-CHOP and R-CHOP provided no significant difference in 5-year OS or PFS in previously untreated patients with low or low-intermediate risk DLBCL.

Abstract Background The triglyceride-glucose (TyG) index has been linked to the onset, progression, and prognosis of cardiovascular disease (CVD) in middle-aged and elderly individuals. Nevertheless, the relationship between the TyG index and impaired cardiovascular fitness (CVF) remains unexplored in non-diabetic young population. Methods We used data from the National Health and Nutrition Examination Survey (NHANES) study (1999–2004) to conduct a cross-sectional study of 3364 participants who completed an examination of CVF. Impaired CVF was defined as low and moderate CVF levels determined by estimated maximal oxygen consumption (Vo2max), based on sex- and age-specific criteria. The TyG index was calculated by $$Ln[TG(mg/dL)\times FPG(mg/dl)/2]$$ L n [ T G ( m g / d L ) × F P G ( m g / d l ) / 2 ] . Results The age (median with interquartile range) of the study population was 28 (19–37) years, and the TyG index (median ± standard deviation) was 8.36 ± 0.52. A significant association between the TyG index and impaired CVF was found in multivariable logistical regression analysis (per 1-unit increase in the TyG index: OR, 1.46; 95% Cl 1.13–1.90). A dose‒response relationship between the TyG index and impaired CVF was presented by restricted cubic splines (RCS). A significant interaction (p = 0.027) between sex and the TyG index for impaired CVF was found in the population aged

The lever or the lever-type mechanism can achieve an inertia amplification effect by appropriately calibrating its structural configuration, and it is also proven to be one of the most cost-effective solution for the inerter realization compared with other mechanical devices. Benefitting from this property, the present paper adopted a new type of tuned lever inerter-like mass damper (TLIMD) for attenuating stochastic load-induced structure dynamic responses. A set of closed-form formulae for the TLIMD optimal parameters are developed by the use of H2 norm optimization criterion, wherein the structure’s inherent damping is explicitly accounted for. It is theoretically demonstrated that the TLIMD optimal parameters are mainly dominated by three critical parameters, i.e., the damper mass ratio, the lever length ratio (known as the inertia amplification ratio) and also the host structural damping. The proposed formulae for the TLIMD optimization are validated through the seismic analysis, where two classic inerter-based dampers (i.e., the tuned mass damper inerter (TMDI) and the tuned inerter damper (TID)) optimized by the numerical technique are included in the discussion. It is found that the TLIMD has a superior advantage in reducing the structure responses and also exhibits stronger robustness for the detuning condition than the classic inerter-based dampers. Furthermore, the increase in the damper mass ratio and the lever length ratio can be beneficial for enhancing its performance.

Sepia esculenta is a tasty and nutritious cephalopod. But the trend toward global warming is accelerating with massive emissions of greenhouse gases. An increase in seawater temperature and a decrease in pH are a great challenge for artificial breeding and culture of S. esculenta. In this study, we investigated the contingency mechanism of S. esculenta larvae under both high temperature and low pH conditions by transcriptome analysis. A total of 1235 DEGs were identified. functional enrichment analysis results suggest that high temperature and low pH conditions led to malignant proliferation in exceptional cells of S. esculenta larvae. A comprehensive analysis of the KEGG signaling pathway and protein-protein interaction network (PPI) identified sixteen key genes under both high temperature and low pH conditions. The three genes with the highest quantities of interactions or involved in more KEGG signaling pathways were identified as hub genes affecting normal physiological processes in S. esculenta. In this study, the effects of global warming and ocean acidification on the metabolism and immunity of S. esculenta larvae were preliminarily investigated to provide necessary help for S. esculenta captive breeding in the face of global climate change.

Pathogenic infections significantly limit the culture of marine organisms, such as cephalopods. However, there is a lack of immune information regarding cephalopods to address pathogen problems. Polyriboinosinic polyribocytidylic acid (Poly I:C), a synthetic virus-like molecule, can be recognized by the immune cells as pathogen-associated molecular patterns (PAMPs), and this process is often used to simulate the invasion of viruses. The white body is an immune and hematopoietic organ, and its RNA-seq information obtained from Amphioctopus fangsiao stimulated by Poly I:C is essential for understanding the antiviral immune response in this species. In this research, we performed transcriptome sequencing and bioinformatics analysis of A. fangsiao white body tissue within 24 h stimulated by Poly I:C. A large number of differentially expressed genes (DEGs) were detected in this study, including 2,613 and 8 DEGs at 6 h and 24 h, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used for searching immune-related terms and genes. A protein–protein interaction (PPI) network was constructed to identify the relationship between immune genes. Finally, the 20 hub genes including RAC1, MAPK14, PIK3CA and other seventeen hub genes were identified based on the network and pathway analyses, and we validated the accuracy of 20 hub genes using qRT-PCR. These hub genes mainly participated in PI3K-Akt signaling pathway, Chemokine signaling pathway and other signaling pathways, in addition to the ubiquitin family. These research results provided a valuable theoretical basis for researching A. fangsiao white body immunity and significantly improved our cognition about innate immunity of cephalopods.

Abstract Background To explore the effects of monitoring measurable residual disease and post‐remission treatment selection on the clinical outcomes of B‐cell acute lymphoblastic leukemia (B‐ALL) in adults. Methods Between September 2010 and January 2022, adult patients with B‐ALL who received combination chemotherapy, with or without allogeneic hematopoietic stem cell transplantation (allo‐HSCT), were included in the retrospective study, which was approved by the Ethics Committee and the observation of Declaration of Helsinki conditions. Results One hundred and forty‐three B‐ALL patients achieved complete remission (CR) were included in the study, of whom 94 patients (65.7%) received allo‐HSCT in first complete remission (CR1). Multivariate analysis showed that the most powerful factors affecting OS were transplantation (hazard ratio [HR] = 0.540, p = 0.037) and sustained measurable residue disease (MRD) negativity (HR = 0.508, p = 0.037). The subgroup analysis showed that the prognosis of the allo‐HSCT group was better than that of the chemotherapy group, regardless of whether MRD was negative or positive after two courses of consolidation therapy. After consolidation therapy, the prognosis of patients with positive MRD remained significantly better in the allo‐HSCT group than in the chemotherapy group. However, no significant difference was observed in the prognosis between the allo‐HSCT and chemotherapy groups with negative MRD after consolidation therapy. Conclusions B‐ALL patients who achieve sustained MRD negativity during consolidation therapy have excellent long‐term outcomes even without allo‐HSCT. Allo‐HSCT is associated with a significant benefit in terms of OS and DFS for patients who were with positive MRD during consolidation therapy.

Abstract Silver nanowire (AgNW) networks hold great promises as next‐generation flexible transparent electrodes (FTEs) for high‐performance flexible optoelectronic devices. However, achieving large‐area flexible AgNW network electrodes with low sheet resistance, high optical transmittance, and a smooth surface remains a grand challenge. Here, we report a straightforward and cost‐effective roll‐to‐roll method that includes interface assembly/wetting‐induced climbing transfer, nanowelding, and washing processess to fabricate flexible ordered layered AgNW electrodes with high network uniformity. By manipulating the stacking number of the interfacially assembled AgNW monolayer, we can precisely tailor and balance the transparency and the conductivity of the electrodes, achieving an exceptional Figure of Merit (FoM) value of 862. Moreover, the ordered layered structure enhances surface smoothness, compared with randomly arranged structures. To highlight the potential of these ordered layered AgNW network electrodes in flexible optoelectronic devices, we successfully employ them as highly sensitive strain sensors, large‐area flexible touch screens, and flexible smart windows. Overall, this work represents a substantial advance toward high‐performance FTEs over large areas, opening up exciting opportunities for the development of advanced optoelectronic devices.

BackgroundThe renin-angiotensin-aldosterone system (RAAS) members, especially Ang II and aldosterone, play key roles in the pathogenesis of diabetic cardiomyopathy (DCM). Angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers combined with aldosterone receptor antagonists (mineralocorticoid receptor antagonists) have substantially improved clinical outcomes in patients with DCM. However, the use of the combination has been limited due to its high risk of inducing hyperkalemia.MethodsType 1 diabetes was induced in 8-week-old male C57BL/6J mice by intraperitoneal injection of streptozotocin at a dose of 55 mg/kg for 5 consecutive days. Adeno-associated virus 9-mediated short-hairpin RNA (shRNA) was used to knock down the expression of ADAM17 in mice hearts. Eplerenone was administered via gavage at 200 mg/kg daily for 4 weeks. Primary cardiac fibroblasts were exposed to high glucose (HG) in vitro for 24 h to examine the cardiac fibroblasts to myofibroblasts transformation (CMT).ResultsCardiac collagen deposition and CMT increased in diabetic mice, leading to cardiac fibrosis and dysfunction. In addition, ADAM17 expression and activity increased in the hearts of diabetic mice. ADAM17 inhibition and eplerenone treatment both improved diabetes-induced cardiac fibrosis, cardiac hypertrophy and cardiac dysfunction, ADAM17 deficiency combined with eplerenone further reduced the effects of cardiac fibrosis, cardiac hypertrophy and cardiac dysfunction compared with single therapy in vivo. High-glucose stimulation promotes CMT in vitro and leads to increased ADAM17 expression and activity. ADAM17 knockdown and eplerenone pretreatment can reduce the CMT of fibroblasts that is induced by high glucose levels by inhibiting TGFβ1/Smad3 activation; the combination of the two can further reduce CMT compared with single therapy in vitro.ConclusionOur findings indicated that ADAM17 knockout could improve diabetes-induced cardiac dysfunction and remodeling through the inhibition of RAAS overactivation when combined with eplerenone treatment, which reduced TGF-β1/Smad3 pathway activation-mediated CMT. The combined intervention of ADAM17 deficiency and eplerenone therapy provided additional cardiac protection compared with a single therapy alone without disturbing potassium level. Therefore, the combination of ADAM17 inhibition and eplerenone is a potential therapeutic strategy for human DCM.

Nanoplastics (NPs, < 1 μm) have attracted widespread attention due to their potential threats to organisms, ecosystem, and public health. However, there is limited research on the effects of NPs on cephalopods. Sepia esculenta (Mollusks, Cephalopoda, Sepioidea), an economically major species of Sepiidea family in the world, is well received by consumers for its delicious quality and rich nutrition. In the present study, S. esculenta larvae were treated with polystyrene nanoplastics (PS-NPs) at 50 μg/mL for 4 h, and then physiological biomarkers (SOD, GSTs and MDA) and RNA-Seq in the whole body were performed. Research results suggested that PS-NPs exposure had induced oxidative stress of S. esculenta larvae. In addition, several key genes and signaling pathways related to oxidative stress were obtained based on DEGs, GO and KEGG enrichment analyses, as well as PPI construction analysis of transcriptome data. This study enriches the research on the effects of NPs exposure on different organisms and provides insights and references for revealing the mechanisms of oxidative stress caused at the molecular level.

Spermatogenesis is the production of spermatozoa by the testes, a process that is associated with reproduction in males. Amphioctopus fangsiao is an economically important species from the northern coast of China, and little research has been done on spermatogenesis in this species. In this study, we performed transcriptome analysis of testis and other somatic tissues. The maturing stage of testis development was selected, in which the emergence of spermatozoa was observed. A total of 15,773 differentially expressed genes were identified, including 8,922 upregulated genes and 6,851 downregulated genes. GO and KEGG enrichment analyses were performed to explore the functions of genes related to spermatogenesis, and the interactions between genes were examined by constructing protein interaction networks. Pathways and genes related to spermatogenesis were identified, including the oxytocin signaling pathway, the calcium signaling pathway, the FOXO signaling pathway, the DNAH family, and other key genes. The expression levels of 25 key genes were verified by qRT-PCR. The results for spermatogenesis-related genes will provide insights into the processes of spermatogenesis and testis development in A. fangsiao.

Marine mollusks, including oysters, are highly tolerant to high levels of cadmium (Cd), but the molecular mechanisms underlying their molecular response to acute Cd exposure remain unclear. In this study, the Pacific oyster Crassostrea gigas was used as a biological model, exposed to acute Cd stress for 96 h. Transcriptomic analyses of their gills were performed, and metabolomic analyses further validated these results. In our study, a total of 111 differentially expressed metabolites (DEMs) and 2108 differentially expressed genes (DEGs) were identified under acute Cd exposure. Further analyses revealed alterations in key genes and metabolic pathways associated with heavy metal stress response. Cd exposure triggered physiological and metabolic responses in oysters, including enhanced oxidative stress and disturbances in energy metabolism, and these changes revealed the biological response of oysters to acute Cd stress. Moreover, oysters could effectively enhance the tolerance and detoxification ability to acute Cd exposure through activating ABC transporters, enhancing glutathione metabolism and sulfur relay system in gill cells, and regulating energy metabolism. This study reveals the molecular mechanism of acute Cd stress in oysters and explores the molecular mechanism of high tolerance to Cd in oysters by using combined metabolomics and transcriptome analysis.

More and more underwater robots are deployed to investigate marine biodiversity autonomously, and tools are needed by underwater robots to discover and acknowledge marine life. This paper has proposed a convolutional neural network-based method for intelligent fish detection and recognition with a dataset used for training and testing generated and augmented from an open-source Fish Database regarding 6 different types. Firstly, to improve image quality, a hybrid image enhancement algorithm is used to preprocess underwater images with a weighted fusion strategy of multiple traditional methodologies and comparisons have been made to prove the effectiveness according to various indexes. Secondly, to increase detection and recognition accuracy, different attention modules are integrated into the YOLOv5m network structure and the convolutional block attention module(CBAM) has outperformed other modules in recall rate and mAP while maintaining the capability of real-time processing. Lastly, to meet real-time requirements, lightweight adjustments have been made to CBAM-YOLOv5m with the GSConv module and C3Ghost module and a nearly 25% reduction in network parameters and a 20% reduction in computational consumption are obtained. Besides, the lightweight network has realized better accuracy than YOLOv5m. In conclusion, the method proposed in this paper is effective in real-time fish detection and recognition with practical application prospects.

Near-infrared spectroscopy (NIR) has become an essential tool for non-destructive analysis in various fields, including aquaculture. This study presents a pioneering application of portable NIR spectrometers to analyze glycogen content in the gonadal tissues of the Pacific oyster (Crassostrea gigas), marking the first instance of developing quantitative models for glycogen in tetraploid C. gigas. The research also provides a comparative analysis with models for diploid and triploid oysters, underscoring the innovative use of portable NIR technology in aquaculture. Two portable NIR spectrometers were employed: the Micro NIR 1700 (908–1676 nm) and the Micro PHAZIR RX (1624–2460 nm). Near-infrared spectra were acquired from the gonadal tissues of diploid, triploid, and tetraploid C. gigas. Quantitative models for glycogen content were developed and validated using cross-validation methods. Additionally, qualitative models for different ploidies and genders were established. For the Micro NIR 1700, the cross-validation correlation coefficients (Rcv) and cross-validation relative predictive errors (RPDcv) for glycogen were 0.949 and 3.191 for diploids, 0.915 and 2.498 for triploids, and 0.902 and 2.310 for tetraploids. The Micro PHAZIR RX achieved Rcv and RPDcv values of 0.781 and 2.240 for diploids, 0.839 and 2.504 for triploids, and 0.717 and 1.851 for tetraploids. The Micro NIR 1700 demonstrated superior quantitative performance, with RPD values exceeding 2, indicating its effectiveness in predicting glycogen content across different ploidy levels. Qualitative models showed a performance index of 91.6 for diploid and 95 for tetraploid genders using the Micro NIR 1700, while the Micro PHAZIR RX achieved correct identification rates of 99.79% and 100% for diploid and tetraploid genders, respectively. However, differentiation of ploidies was less successful with both instruments. This study’s originality lies in establishing the first quantitative models for glycogen content in tetraploid C. gigas using portable NIR spectrometers, highlighting the significant advancements in non-destructive glycogen analysis. The applicability of these findings is substantial for oyster breeding programs focused on enhancing meat quality traits. These models provide a valuable phenotyping tool for selecting oysters with optimal glycogen content, demonstrating the practical utility of portable NIR technology in aquaculture.

Abstract Endothelial dysfunction represents a major cardiovascular risk factor for hypertension. Sp1 and Sp3 belong to the specificity protein and Krüppel-like transcription factor families. They are ubiquitously expressed and closely associated with cardiovascular development. We investigate the role of Sp1 and Sp3 in endothelial cells in vivo and evaluate whether captopril, an angiotensin-converting enzyme inhibitor (ACEI), targets Sp1/Sp3 to exert its effects. Inducible endothelial-specific Sp1/Sp3 knockout mice are generated to elucidate their role in endothelial cells. Tamoxifen-induced deletion of endothelial Sp1 and Sp3 in male mice decreases the serum nitrite/nitrate level, impairs endothelium-dependent vasodilation, and causes hypertension and cardiac remodeling. The beneficial actions of captopril are abolished by endothelial-specific deletion of Sp1/Sp3, indicating that they may be targets for ACEIs. Captopril increases Sp1/Sp3 protein levels by recruiting histone deacetylase 1, which elevates deacetylation and suppressed degradation of Sp1/Sp3. Sp1/Sp3 represents innovative therapeutic target for captopril to prevent cardiovascular diseases.

Abstract Background The triglyceride-glucose (TyG) index has been evaluated as a reliable surrogate for insulin resistance (IR) and has been proven to be a predictor of poor outcomes in patients with cardiovascular diseases. However, data are lacking on the relationship of the TyG index with prognosis in nondiabetic patients who underwent coronary artery bypass grafting (CABG). Thus, the purpose of our current study was to investigate the potential value of the TyG index as a prognostic indicator in patients without diabetes mellitus (DM) after CABG. Methods This multicenter, retrospective cohort study involving 830 nondiabetic patients after CABG from 3 tertiary public hospitals from 2014 to 2018. Kaplan–Meier survival curve analysis was conducted followed by the log-rank test. Cox proportional hazards regression models were used to explore the association between the TyG index and major adverse cardiovascular events (MACEs). The incremental predictive power of the TyG index was evaluated with C-statistics, continuous net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Results An incrementally higher TyG index was associated with an increasingly higher cumulative incidence of MACEs (log-rank test, p

Abstract Background Cadmium (Cd) flows into the ocean with industrial and agricultural pollution and significantly affects the growth and development of economic cephalopods such as Sepia esculenta, Amphioctopus fangsiao, and Loligo japonica. As of now, the reasons why Cd affects the growth and development of S. esculenta are not yet clear. Results In this study, transcriptome and four oxidation and toxicity indicators are used to analyze the toxicological mechanism of Cd-exposed S. esculenta larvae. Indicator results indicate that Cd induces oxidative stress and metal toxicity. Functional enrichment analysis results suggest that larval ion transport, cell adhesion, and some digestion and absorption processes are inhibited, and the cell function is damaged. Comprehensive analysis of protein-protein interaction network and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was used to explore S. esculenta larval toxicological mechanisms, and we find that among the 20 identified key genes, 14 genes are associated with neurotoxicity. Most of them are down-regulated and enriched to the neuroactive ligand-receptor interaction signaling pathway, suggesting that larval nervous system might be destroyed, and the growth, development, and movement process are significantly affected after Cd exposure. Conclusions S. esculenta larvae suffered severe oxidative damage after Cd exposure, which may inhibit digestion and absorption functions, and disrupt the stability of the nervous system. Our results lay a function for understanding larval toxicological mechanisms exposed to heavy metals, promoting the development of invertebrate environmental toxicology, and providing theoretical support for S. esculenta artificial culture.

Abstract Foam cell formation is a hallmark of the early phase of atherosclerosis. Growing evidence has demonstrated that vascular smooth muscle cells (VSMCs) comprise a considerable proportion of foam cells. Liver kinase B1 (LKB1) plays a crucial part in cardiovascular diseases. However, the role of LKB1 in VSMC-derived foam cell formation and atherosclerosis remains unclear. To explore the effects of LKB1 on VSMC-derived foam cell formation and atherosclerosis, we generated smooth muscle-specific LKB1 knockout (LKB1SMKO) mice by crossbreeding LKB1flox/flox mice with SM22α-CreERT2 mice. LKB1 expression decreased in plaque-loaded aortas and oxidized low-density lipoprotein (oxLDL)-treated VSMCs. Compared with controls, atherosclerosis development was exacerbated in LKB1SMKO mice via the promotion of VSMC-derived foam cell formation. Conversely, LKB1 overexpression inhibited lipid uptake and foam cell formation in VSMCs. Mechanistically, LKB1 binds to SIRT6 and directly phosphorylates and activates it, thereby reducing lectin-like oxLDL receptor-1 (LOX-1) via SIRT6-dependent histone deacetylation. Finally, adeno-associated virus (AAV)-mediated LOX-1 deficiency in smooth muscle ameliorated atherosclerosis in LKB1SMKO mice. Our findings suggest that LKB1 may modulate VSMC-derived foam cell formation and atherosclerosis via the phosphorylation and activation of SIRT6.

Abstract Previous studies suggested a beneficial effect of natriuretic peptides in animal models of cardiovascular disease, but the role of natriuretic peptide receptor C (NPRC) in the pathogenesis of atherosclerosis (AS) remains unknown. This study was designed to test the hypothesis that NPRC may promote AS lesion formation and instability by enhancing oxidative stress, inflammation, and apoptosis via protein kinase A (PKA) signaling. ApoE−/− mice were fed chow or Western diet for 12 weeks and NPRC expression was significantly increased in the aortic tissues of Western diet-fed mice. Systemic NPRC knockout mice were crossed with ApoE−/− mice to generate ApoE−/−NPRC−/− mice, and NPRC deletion resulted in a significant decrease in the size and instability of aortic atherosclerotic lesions in ApoE−/−NPRC−/− versus ApoE−/− mice. In addition, endothelial cell-specific NPRC knockout attenuated atherosclerotic lesions in mice. In contrast, endothelial cell overexpression of NPRC aggravated the size and instability of atherosclerotic aortic lesions in mice. Experiments in vitro showed that NPRC knockdown in human aortic endothelial cells (HAECs) inhibited ROS production, pro-inflammatory cytokine expression and endothelial cell apoptosis, and increased eNOS expression. Furthermore, NPRC knockdown in HAECs suppressed macrophage migration, cytokine expression, and phagocytosis via its effects on endothelial cells. On the contrary, NPRC overexpression in endothelial cells resulted in opposite effects. Mechanistically, the anti-inflammation and anti-atherosclerosis effects of NPRC deletion involved activation of cAMP/PKA pathway, leading to downstream upregulated AKT1 pathway and downregulated NF-κB pathway. In conclusion, NPRC deletion reduced the size and instability of atherosclerotic lesions in ApoE−/− mice via attenuating inflammation and endothelial cell apoptosis and increasing eNOS expression by modulating cAMP/PKA-AKT1 and NF-κB pathways. Thus, targeting NPRC may provide a promising approach to the prevention and treatment of atherosclerosis.

Abstract Background The metabolic score for insulin resistance (METS-IR) is a simple, convenient, and reliable marker for resistance insulin (IR), which has been regarded as a predictor of cardiovascular disease (CVD) and cardiovascular events. However, few studies examined the relationship between METS-IR and prognosis after coronary artery bypass graft (CABG). This study aimed to investigate the potential value of METS-IR as a prognostic indicator for the major adverse cardiovascular events (MACE) in patients after CABG. Method 1100 CABG patients were enrolled in the study, including 760 men (69.1%) and 340 women (30.9%). The METS-IR was calculated as Ln [(2 × FPG (mg/dL) + fasting TG (mg/dL)] × BMI (kg/m2)/Ln [HDL-C (mg/dL)]. The primary endpoint of this study was the occurrence of major adverse cardiovascular events (MACE), including a composite of all-cause death, non-fatal myocardial infarction (MI), coronary artery revascularization, and stroke. Result The following-up time of this study was 49–101 months (median, 70 months; interquartile range, 62–78 months). During the follow-up period, there were 243 MACEs (22.1%). The probability of cumulative incidence of MACE increased incrementally across the quartiles of METS-IR (log-rank test, p

The emergence of triploid oysters has freed the oyster market from the problem of interruptions in the breeding season, allowing for year-round availability. However, according to recent statistics, the phenomenon of fertility in triploid oysters has been increasing yearly, perhaps eventually leading to the loss of the sterility characteristic. This has in turn affected the oyster farming industry. Therefore, we attempted to mine key genes through transcriptomics to find the causes of triploid fertility. During our surveys and sampling, we found that most of the fertile triploid Crassostrea gigas were females, with a much smaller percentage of males. Therefore, the main objective of this study was to analyze the differences between fertile and sterile triploid female C. gigas. We performed transcriptome analysis of fertile female triploid C. gigas and sterile female triploid C. gigas and identified 2361 up-regulated differentially expressed genes (DEGs) and 1541 down-regulated DEGs, respectively. Enrichment analysis of these DEGs revealed that most GO terms and KEGG pathways were associated with mitosis. We then created a protein–protein interaction (PPI) network using genes enriched in mitosis-associated KEGG pathways. Finally, we screened and validated 26 key genes by quantitative RT-PCR and all were found to be downregulated in expression in sterile female triploids. The main cause of sterility is the suppression of the expression of genes that control the process of germ cell proliferation, the failure of the mitotic cycle to proceed smoothly, and the inability to produce an oogonium. These results can be used to explore ways to reduce the fertility of triploid C. gigas and to promote the breeding of higher quality triploid oysters.

BackgroundThere were seven novel and easily accessed insulin resistance (IR) surrogates established, including the Chinese visceral adiposity index (CVAI), the visceral adiposity index (VAI), lipid accumulation product (LAP), triglyceride glucose (TyG) index, TyG-body mass index (TyG-BMI), TyG-waist circumference (TyG-WC) and TyG-waist to height ratio (TyG-WHtR). We aimed to explore the association between the seven IR surrogates and incident coronary heart disease (CHD), and to compare their predictive powers among Chinese population.MethodsThis is a 10-year prospective cohort study conducted in China including 6393 participants without cardiovascular disease (CVD) at baseline. We developed Cox regression analyses to examine the association of IR surrogates with CHD (hazard ratio [HR], 95% confidence intervals [CI]). Moreover, the receiver operating characteristic (ROC) curve was performed to compare the predictive values of these indexes for incident CHD by the areas under the ROC curve (AUC).ResultsDuring a median follow-up period of 10.25 years, 246 individuals newly developed CHD. Significant associations of the IR surrogates (excepted for VAI) with incident CHD were found in our study after fully adjustment, and the fifth quintile HRs (95% CIs) for incident CHD were respectively 2.055(1.216-3.473), 1.446(0.948-2.205), 1.753(1.099-2.795), 2.013(1.214-3.339), 3.169(1.926-5.214), 2.275(1.391-3.719) and 2.309(1.419-3.759) for CVAI, VAI, LAP, TyG, TyG-BMI, TyG-WC and TyG-WHtR, compared with quintile 1. Furthermore, CVAI showed maximum predictive capacity for CHD among these seven IR surrogates with the largest AUC: 0.632(0.597,0.667).ConclusionThe seven IR surrogates (excepted for VAI) were independently associated with higher prevalence of CHD, among which CVAI is the most powerful predictor for CHD incidence in Chinese populations.

Sterile α motif and histidine/aspartic acid domain containing protein 1 (SAMHD1) is a deoxynucleoside triphosphate (dNTPs) triphosphohydrolase that can hydrolyze dNTPs into deoxynucleosides and triphosphates to keep the balance of the intracellular dNTPs pool. Moreover, it has been reported that SAMHD1 plays a role in regulating cell proliferation and the cell cycle, maintaining genome stability and inhibiting innate immune responses. SAMHD1 activity is regulated by phosphorylation, oxidation, SUMOylation, and O-GlcNAcylation. SAMHD1 mutations have been reported to cause diseases, including chronic lymphocytic leukemia and mantle cell lymphoma. SAMHD1 expression in acute myeloid leukemia predicts inferior prognosis. Recently, it has been revealed that SAMHD1 mediates the resistance to anti-cancer drugs. This review will focus on SAMHD1 function and regulation, the association between SAMHD1 and hematological malignancies and will provide updated information on SAMHD1 mediating resistance to nucleoside analogue antimetabolites, topoisomerase inhibitors, platinum-derived agents and DNA hypomethylating agents. Furthermore, histone deacetylase inhibitors and tyrosine kinase inhibitors indirectly increase anti-cancer drug resistance by increasing SAMDH1 activity. We herein highlight the importance of the development of novel agents targeting SAMHD1 to overcome treatment resistance of hematological malignancies, which would be an opportunity to improve the outcome of patients with refractory hematological malignancies.