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Abstract A large scale of distributed photovoltaics is accessed through a low voltage distribution network in a single‐phase or two‐phase, which causes three‐phase unbalance and over‐voltage problems. These problems can be solved by using a voltage source converter to realize AC/DC interconnection and flexible power transfer between lines. How to utilize the characteristics of voltage source converters to optimize the power qualities, and fully promote distributed PV systems consumption in low voltage distribution network is an important research point. This paper proposes a power regulation model of VSC. The goal of this model is to adjust and optimize over‐voltage and three‐phase unbalance problems. By constructing a voltage‐power sensitivity calculation model for a three‐phase four‐wire system and integrating different control modes and adjustment capabilities of voltage source converters, a control strategy based on voltage source converters is proposed to address three‐phase unbalance and over‐voltage issues. Finally, the simulation results demonstrate the effectiveness of the proposed strategy.

Abstract A high‐salt diet can induce hypertension, so salt reduction can prevent hypertension. γ‐Glutamyl peptides (GGPs) have obvious taste‐enhancing effects, while their contents in natural foods are relatively low. Yeast protein rich in Glu/Gln is a good precursor for the preparation of GGPs. In this study, yeast protein‐derived GGPs were prepared through hydrolysis and transpeptidation reactions, followed by sensory evaluation and E‐tongue analysis. Peptide sequences were identified by LC−MS/MS and screened for molecular docking. The optimal reaction conditions were hydrolysis for 4 h, enzyme concentration of 16 U/g, and transpeptidation for 4 h. GGPs could increase salt and umami intensity by 60.78% and 40.93% based on sensory evaluation, 22.52%, and 16.40% according to E‐tongue analysis. Fifteen γ‐glutamyl peptides with different peptide lengths were selected for molecular docking. Molecular docking confirmed their binding to calcium‐sensing receptors (CaSr) through hydrogen bonds and hydrophobic interaction, while interaction between CaSR receptor and γ‐glutamyl di‐, tri‐, and oligo‐peptides varied in binding energy. The stimulation received by CaSR lasted a longer time and varied in intensity. It was further proved that the flavor of mixed peptides has a layered sense and can give people a rich taste experience. Overall, yeast protein‐derived GGPs can enhance salt and umami taste, which can reduce salt usage without compromising taste.

Abstract Stimulator of interferon genes (STING) is vital in the cytosolic DNA-sensing process and critical for initiating the innate immune response, which has important functions in host defense and contributes to the pathogenesis of inflammatory diseases. Zinc finger CCCH-type antiviral protein 1 (ZC3HAV1) specifically binds the CpG dinucleotides in the viral RNAs of multiple viruses and promotes their degradation. ZAPS (ZC3HAV1 short isoform) is a potent stimulator of retinoid acid-inducible gene I (RIG-I) signaling during the antiviral response. However, how ZC3HAV1 controls STING signaling is unclear. Here, we show that ZC3HAV1 specifically potentiates STING activation by associating with STING to promote its oligomerization and translocation from the endoplasmic reticulum (ER) to the Golgi, which facilitates activation of IRF3 and NF-κB pathway. Accordingly, Zc3hav1 deficiency protects mice against herpes simplex virus-1 (HSV-1) infection- or 5,6-dimethylxanthenone-4-acetic acid (DMXAA)-induced inflammation in a STING-dependent manner. These results indicate that ZC3HAV1 is a key regulator of STING signaling, which suggests its possible use as a therapeutic target for STING-dependent inflammation.

Abstract Recent advancements in bacterial two-component systems (TCS) have spurred research into TCS-based biosensors, notably for their signal amplification and broad input responsiveness. The CusRS system in Escherichia coli (E. coli), comprising cusS and cusR genes, is a copper-sensing module in E. coli. However, due to insufficient sensing performance, CusRS-based biosensors often cannot meet practical requirements. To address this issue, we made improvements and innovation from several aspects. CusR and CusS expression were adjusted to enhance the Cu(II) biosensor’s performance. A copy-number inducible plasmid was used for signal amplification, while removing copper detox genes cueO and cusCFBA improved sensitivity and lowered detection limits. Ultimately, in the optimized biosensor of Cu26, the fold-change (I/I0) increased from 1.5-fold to 18-fold at 1 μM, rising to 100-fold after optimizing the cell culture procedure. The biosensor’s high fluorescence enabled rapid, instrument-free detection and an improved analysis strategy reduced the detection limit to 0.01 μM, surpassing traditional methods.

Abstract SS18-SSX onco-fusion protein formed through aberrant chromosomal translocation t (X, 18; p11, q11), is the hallmark and plays a critical role in synovial sarcomagenesis. The recent works indicated that both the pathological SS18-SSX tumorigenic fusion and the corresponding intrinsic physiological SS18 protein can form condensates but appear to have disparate properties. The underlying regulatory mechanism and the consequent biological significance remain largely unknown. We show that the physical properties of oncogenic fusion protein SS18-SSX condensates within cells undergo alterations compared to the proto-oncogene protein SS18. By small-molecule screening and mutant assay, we identified the recognition of H2AK119ub histone modification could account for the distinctive properties of SS18-SSX1 condensates. Notably, we show that SS18-SSX1 condensates have impact on SS18 condensates and hijack that in a phase separation manner, resulting in the relocation of protein SS18 to the H2AK119ub modification targeted by SS18-SSX1. Consequently, this leads to the downregulation of tumor suppressor genes occupied by SS18 physiologically, like CAV1 and DAB2. These results reveal the underlying mechanism of genomic disorder and tumorigenesis caused by the remodeling of oncoprotein SS18-SSX1 condensates at the macroscopic level.

Abstract Sepsis-induced acute lung injury (ALI), characterized by severe hypoxemia and pulmonary leakage, remains a leading cause of mortality in intensive care units. The exacerbation of ALI during sepsis is largely attributed to uncontrolled inflammatory responses and endothelial dysfunction. Emerging evidence suggests an important role of Z-DNA binding protein 1 (ZBP1) as a sensor in innate immune to drive inflammatory signaling and cell death during infections. However, the role of ZBP1 in sepsis-induced ALI has yet to be defined. We utilized ZBP1 knockout mice and combined single-cell RNA sequencing with experimental validation to investigate ZBP1’s roles in the regulation of macrophages and lung endothelial cells during sepsis. We demonstrate that in sepsis, ZBP1 deficiency in macrophages reduces mitochondrial damage and inhibits glycolysis, thereby altering the metabolic status of macrophages. Consequently, this metabolic shift leads to a reduction in the differentiation of macrophages into pro-inflammatory states and decreases macrophage pyroptosis triggered by activation of the NLRP3 inflammasome. These changes significantly weaken the inflammatory signaling pathways between macrophages and endothelial cells and alleviate endothelial dysfunction and cellular damage. These findings reveal important roles for ZBP1 in mediating multiple pathological processes involved in sepsis-induced ALI by modulating the functional states of macrophages and endothelial cells, thereby highlighting its potential as a promising therapeutic target.

Abstract Klebsiella pneumoniae is among the most important Gram-negative pathogens that can cause serious nosocomial infections. The emergence and prevalence of hypervirulent carbapenem-resistant K. pneumoniae (Hv-CRKP) pose a significant challenge to public health. In this study, we characterized thirty carbapenem-resistant K. pneumoniae (CRKP) strains from a tertiary care hospital in Sichuan province, China, by whole-genome sequencing and genome analysis. These strains were all highly resistant to carbapenem but remained susceptible to tigecycline. Of the 30 tested CRKP strains, 23 were positive for bla KPC−2 and seven for bla NDM−5. These bla KPC−2-positive strains all belonged to ST11, while bla NDM−5-positive strains belonged to five distinct STs. Phylogenetic analysis revealed a predominant intra-hospital transmission of ST11-KL64 in KPC-2-producing CRKP, and that both clonal and horizontal transmission of bla NDM−5 have occurred among NDM-5-producing CRKP strains in this hospital. Hypervirulence genes were commonly detected in the CRKP. The prevalent pLVKP-like plasmid and ICEKp seem to have contributed largely to the transmission of virulence genes in them. bla NDM−5 was located on highly similar IncX3 plasmids in the collected strains, and its truncated vision was highlighted. bla KPC−2 was primarily carried by IncFII/IncR plasmids in our collection. At least two IncFII/IncR plasmid subtypes were identified, exhibiting high similarity to many previously reported bla KPC−2-bearing plasmids from different parts of China. The findings provide an expanded knowledge of the genetic characteristics of CRKP, the transmission pattern of carbapenem-resistance genes, and also the convergence of Hv-CRKP.

Abstract Background As a potential model organism for studies of environmental and cell biology, Paramecium duboscqui is a special euryhaline species of Paramecium that can be found in fresh, brackish, or marine water in natural salinity ranges between 0‰ and 33‰. However, the genome information as well as molecular mechanisms that account for its remarkable halotolerant traits remain extremely unknown. To characterize its genome feature, we combined PacBio and Illumina sequencing to assemble the first high-quality and near-complete macronuclear genome of P. duboscqui. Meanwhile, comparative transcriptomic profiles under different salinities gave underlying insight into the molecular mechanism of its adaptations to environmental salinity. Results The results showed that the MAC genome of P. duboscqui comprises 160 contigs, with 113 of them possessing telomere (~ 28.82 Mb haploid genome size). Through comparative genomic analyses with the other ciliate, we found that gene families encoding transmembrane transporter proteins have been expanded in P. duboscqui, showing enormous potential in salinity adaptation. Like other Paramecium, P. duboscqui utilizes TGA as its only termination codon and has reassigned TAA and TAG to encode glutamine. P. duboscqui showed different growth rates under different salinities, with an optimum growth rate in 5‰ salinity. A comparison of the transcriptomic profiles among P. duboscqui grown under different concentrations showed that genes involved in protein folding, oxygen respiration, and glutathione-dependent detoxification were upregulated in the high-salt group, whereas genes encoding DNA-binding proteins and transcription factors were upregulated in the low-salt group, suggesting distinct mechanisms for responding to low and high salinity. Weighted gene coexpression network analysis (WGCNA) linked the hub genes expressed at 30‰ salinity to cysteine-type peptidase activity, lipid transfer, sodium hydrogen exchange, and cell division, with the hub genes expressed at 0‰ salinity involved in transmembrane transport and protein localization. Conclusions This study characterizes a new euryhaline model Paramecium, provides novel insights into Paramecium evolution, and describes the molecular mechanisms that have allow P. duboscqui to adapt to different osmotic environments.

Abstract The present study aims to explore the influence of field cognitive style on the false memory of Chinese characters. Based on the related literature, this paper used Cognitive Style Figure Test (CSFT) to investigate the field cognitive style of college student and test the differences of field cognitive style in demographic variables. Using the DRM paradigm, with Chinese characters lists as experimental material. This study was to inspect whether Chinese semantic/tonetic association has any effect on false memory, and whether there is any interaction between field cognitive style and Chinese character component on it. The results showed that: (a) there were significant differences between male and female in the recognition rate of symbol types, with the recognition rate of tonetic symbol type characters being generally higher than that of semantic symbol type; (b) Chinese semantic/tonetic associations had an effect on false memory and gender has a significant difference in the recognition of critical-lures; (c) field cognitive style had no statistically significant difference in recognition rate on character component type and characters type (old characters, filler characters, and critical-lures); (d) individuals with different field cognitive styles differed significantly in the rate of misrecognition of critical-lures for semantic symbols.

Abstract Metabolism has been implicated in cell fate determination, particularly through epigenetic modifications. Similarly, lipid remodeling also plays a role in regulating cell fate. Here, we present comprehensive lipidomics analysis during BMP4-driven primed to naive pluripotency transition or BiPNT and demonstrate that lipid remodeling plays an essential role. We further identify Cpt1a as a rate-limiting factor in BiPNT, driving lipid remodeling and metabolic reprogramming while simultaneously increasing intracellular acetyl-CoA levels and enhancing H3K27ac at chromatin open sites. Perturbation of BiPNT by histone acetylation inhibitors suppresses lipid remodeling and pluripotency transition. Together, our study suggests that lipid remodeling promotes pluripotency transitions and further regulates cell fate decisions, implicating Cpt1a as a critical regulator between primed-naive cell fate control.

Abstract Background Low back pain has become a globally challenging health problem, and about 90% of cases are nonspecific. Due to the risks associated with opioid use and the limited effectiveness of drug treatment, acupuncture and other non-drug methods have become the first-line treatment for this disease. However, the best acupuncture method has not yet been determined. In this study, the effects of different acupuncture methods on chronic nonspecific low back pain (CNLBP) were compared by network meta-analysis, aiming at identifying the best option and providing a basis for precise treatment of CNLBP. Methods Clinical randomized controlled trials (RCTs) on acupuncture in the treatment of NSLBP were searched in eight databases including PubMed, Embase, Cochrane Library, Web of Science, Sinomed, CNKI, Wanfang Data and VIP from the inception of databases to January 21, 2024. The Cochrane risk-of-bias tool 2.0 (RoB 2.0) and Stata 15.0 (Stata Corp, College Station, Texas, USA) were used to evaluate the literature quality and meta-analysis, and the evidence quality was assessed based on GRADE guidelines. This systematic review was registered at the International Prospective Register of Systematic Reviews. Results A total of 27 articles were included, involving 2579 patients. The results of the network meta-analysis showed that the top three treatment schemes were warm needle acupuncture, intensive silver needle therapy and meridian-sinew theory-based treatment. In terms of relieving pain, the top three treatments were electrical warm needling, intensive silver needle therapy and warm needle acupuncture. In improving mobility, the top three were meridian-sinew theory-based treatment, routine acupuncture and electroacupuncture. Conclusion For CNLBP patients, warm needle acupuncture, electrical warm needling and meridian-sinew theory-based treatment are mainly recommended. If patients have significant pain, electroacupuncture is strongly suggested. On the contrary, for patients with decreased joint mobility, meridian-sinew theory-based treatment is advocated.

This study was aimed to investigate the effects of dietary calcitriol or quercetin supplementation on eggshell and bone quality of laying hens. In trial 1, 72 Hy-Line Brown layers (80-week-old) with weak-shelled strength (25 to 30 N) were assigned into 4 dietary treatments with 6 replicates of 3 birds and fed a basal diet (4% calcium level) or basal diets supplemented with 0.5% calcium, 5 μg/kg calcitriol or 500 mg/kg quercetin for 4 weeks. In trial 2, 360 Hy-Line Brown layers (60-week-old) were divided into 3 groups with 8 replicates of 15 birds: control group (basal diet), calcitriol group (basal diet + 5 μg/kg calcitriol), and quercetin group (basal diet + 500 mg/kg quercetin). This trial lasted for 12 weeks. The results showed that dietary calcitriol or quercetin improved eggshell quality in both trials (P

Abstract The movement towards electrification is entailing deep changes in power systems. On the demand side, the adoption of electric heating (EH) has grown rapidly in recent years. To eliminate the voltage fluctuations caused by the random switching‐on/‐off behaviors of EHs in some application scenes with special‐power‐line in low voltage distribution networks (LVDNs), a swarm‐intelligence‐based coordinated control approach of EHs for voltage stabilization with zero communication burden while guaranteeing the users’ thermal comforts is researched. A novel bird‐perch‐on‐branch (BPB) ‐based swarm intelligence theory is proposed, which reveals the mapping relation between local observations and global states. On this theoretical basis, a multi‐agent reinforcement learning (MARL) framework is developed for the coordinated dispatch of EHs, where the deep‐Q‐network (DQN) algorithm is adopted to learn and generate the optimal control policy for each EH. The implementation of the proposed MADQN‐BPB approach is described based on the principle of centralized‐training and decentralized‐execution. Comparative control performances of MADQN‐BPB with a commercially available approach, and the global optimal solution are evaluated. Simulation results verify the capability of MADQN‐BPB in voltage stabilization with zero communication burden. Its control performance is close to that of the global optimal solution, and is scalable to the variations of environment.

Abstract Background The transposons of the hAT superfamily are the most widespread transposons ever known. SLEEPER genes encode domesticated transposases from the hAT superfamily, which may have lost their transposable functions during long-term evolution and transformed into host proteins that regulate plant growth and development. Results This study identified 162 members of the SLEEPER gene family from Brassica napus. These members are widely distributed on 19 chromosomes, mainly in the Cn subgenome, and have promoters with various cis-acting elements related to hormone regulation, abiotic stress, and growth and development regulation. Most of the genes in this family contain similar conserved domains and motifs, and the closer the genes are distributed on evolutionary branches, the more similar their structures are. Transcriptome sequencing performed on tissues at different growth stages from B. napus line 3529 indicated that these genes had different expression patterns, and nearly half of the genes were not detectably expressed in all samples. Conclusions This study investigated the gene structure, expression patterns, evolutionary features, and gene localization of the SLEEPER family members to confirm the significance of these genes in the growth of B. napus, providing a reference for the study of transposon domestication and outstanding genetic resources for the genetic improvement of B. napus.

Abstract Marine phosphatization events cause episodic carbonate fluorapatite (CFA) precipitation on seamounts, and are commonly linked to growth hiatuses in ferromanganese (Fe-Mn) crusts. However, the complete record of these events and their paleoenvironmental significance remains poorly understood, in large part due to poor age constraints. Here, we apply U-Pb dating to CFA in Fe-Mn crusts from Western Pacific seamounts. These data exhibit good alignment with Sr isotope ages, revealing six potential phosphatization events. This established CFA chronology tightens the timespan of phosphatization events and refines the age framework of Fe-Mn crusts. We subsequently utilize a multiproxy approach to demonstrate that the phosphatization events occurred coeval with the expansion of oceanic oxygen minimum zones. The Western Pacific Fe-Mn crusts thus document major perturbations in global oceanic phosphorus cycling, which appear to have been driven by climate-induced increases in primary productivity linked to changes in global ocean circulation.

Abstract Cell fate decisions remain poorly understood at the molecular level. Embryogenesis provides a unique opportunity to analyze molecular details associated with cell fate decisions. Works based on model organisms have provided a conceptual framework of genes that specify cell fate control, for example, transcription factors (TFs) controlling processes from pluripotency to immunity1. How TFs specify cell fate remains poorly understood. Here we report that SALL4 relies on NuRD (nucleosome-remodeling and deacetylase complex) to interpret BMP4 signal and decide cell fate in a well-controlled in vitro system. While NuRD complex cooperates with SALL4 to convert mouse embryonic fibroblasts or MEFs to pluripotency, BMP4 diverts the same process to an alternative fate, PrE (primitive endoderm). Mechanistically, BMP4 signals the dissociation of SALL4 from NuRD physically to establish a gene regulatory network for PrE. Our results provide a conceptual framework to explore the rich landscapes of cell fate choices intrinsic to development in higher organisms involving morphogen-TF-chromatin modifier pathways.

Abstract Cell fate is likely regulated by a common machinery, while components of this machine remain to be identified. Here we report the design and testing of engineered cell fate controller NanogBiD, fusing BiD or BRG1 interacting domain of SS18 with Nanog. NanogBiD promotes mouse somatic cell reprogramming efficiently in contrast to the ineffective native protein under multiple testing conditions. Mechanistic studies further reveal that it facilitates cell fate transition by recruiting the intended Brg/Brahma-associated factor (BAF) complex to modulate chromatin accessibility and reorganize cell state specific enhancers known to be occupied by canonical Nanog, resulting in precocious activation of multiple genes including Sall4, miR-302, Dppa5a and Sox15 towards pluripotency. Although we have yet to test our approach in other species, our findings suggest that engineered chromatin regulators may provide much needed tools to engineer cell fate in the cells as drugs era.

Abstract Due to the large computational overhead, underutilization of features, and high bandwidth consumption in traditional SDN environments for DDoS attack detection and mitigation methods, this paper proposes a two-stage detection and mitigation method for DDoS attacks in SDN based on multi-dimensional characteristics. Firstly, an analysis of the traffic statistics from the SDN switch ports is performed, which aids in conducting a coarse-grained detection of DDoS attacks within the network. Subsequently, a Multi-Dimensional Deep Convolutional Classifier (MDDCC) is constructed using wavelet decomposition and convolutional neural networks to extract multi-dimensional characteristics from the traffic data passing through suspicious switches. Based on these extracted multi-dimensional characteristics, a simple classifier can be employed to accurately detect attack samples. Finally, by integrating graph theory with restrictive strategies, the source of attacks in SDN networks can be effectively traced and isolated. The experimental results indicate that the proposed method, which utilizes a minimal amount of statistical information, can quickly and accurately detect attacks within the SDN network. It demonstrates superior accuracy and generalization capabilities compared to traditional detection methods, especially when tested on both simulated and public datasets. Furthermore, by isolating the affected nodes, the method effectively mitigates the impact of the attacks, ensuring the normal transmission of legitimate traffic during network attacks. This approach not only enhances the detection capabilities but also provides a robust mechanism for containing the spread of cyber threats, thereby safeguarding the integrity and performance of the network.

Abstract Background Non‐small‐cell lung cancer (NSCLC) is a common malignancy with high morbidity and mortality. Circular RNAs are widely involved in NSCLC progression. However, the mechanism of circSLC25A16 in NSCLC has not been reported. Methods The expressions of circSLC25A16, microRNA‐335‐5p (miR‐335‐5p), and CDGSH iron–sulfur domain‐containing protein 2 (CISD2) were monitored by quantitative real‐time fluorescence polymerase chain reaction. Western blot was also carried out to measure the protein levels of CISD2, hexokinase 2 (HK2), and lactate dehydrogenase A (LDHA). For functional analysis, cell counting kit‐8 assay, 5‐ethynyl‐2′‐deoxyuridine, flow cytometry, transwell, and wound healing assays were utilized to examine cell proliferation, apoptosis, and migration. Glucose uptake and lactate production were detected using commercial kits. The relationship between miR‐335‐5p and circSLC25A16 or CISD2 was verified by dual‐luciferase reporter and RNA immunoprecipitation assays. Furthermore, tumor xenograft was established to explore the function of circSLC25A16 in vivo. Results CircSLC25A16 and CISD2 were overexpressed in NSCLC, but miR‐335‐5p was downregulated. CircSLC25A16 acted as a miR‐335‐5p sponge, and silencing of circSLC25A16 arrested cell proliferation, migration, and glycolysis, and promoted apoptosis, but these impacts were resumed by miR‐335‐5p inhibition. CISD2 was a miR‐335‐5p target, and overexpression of CISD2 abolished the suppressive function of miR‐335‐5p mimic on the malignant behavior of NSCLC cells. CircSLC25A16 could adsorb miR‐335‐5p to mediate CISD2 expression. Additionally, silencing circSLC25A16 restrained the growth of NSCLC tumor xenograft in vivo. Conclusion CircSLC25A16 facilitated NSCLC progression via the miR‐335‐5p/CISD2 axis, implying that circSLC25A16 may serve as a novel biomarker for NSCLC treatment.

Abstract Laser powder bed fusion (LPBF) is an additive manufacturing technology with high practical value. In order to improve the quality of the fabricated parts, process monitoring has become a crucial solution, offering the potential to ensure manufacturing stability and repeatability. However, a cardinal challenge involves discerning a precise correlation between process characteristics and potential defects. This paper elucidates the integration of an off-axis vision monitoring mechanism via a high-speed camera focused on capturing the single-track melting phenomenon. An innovative image processing method was devised to segment the plume and spatters, while Kalman filter was employed for multi-object tracking of the spatters. The features of both the plume and spatters were extracted, and their relationship with molten states was investigated. Finally, the PSO-XGBoost algorithm was utilized to identify five molten states, achieving an accuracy of 92.16%. The novelty of this approach resides in its unique combination of plume characteristics, spatter features, and computationally efficient machine learning models, which collectively address the challenge of limited field of view prevalent in real production scenarios, thereby enhancing process monitoring efficacy. Relative to existing methodologies, the proposed PSO-XGBoost approach offers heightened accuracy, convenience, and appropriateness for the monitoring of the LPBF process. This work provides an effective and novel approach to monitor the LPBF process and evaluate the part fabrication quality for complex and changeable working conditions.

Abstract Background Neurodevelopmental disorders (NDD), such as autism spectrum disorders (ASD) and intellectual disorders (ID), are highly debilitating childhood psychiatric conditions. Genetic factors are recognized as playing a major role in NDD, with a multitude of genes and genomic regions implicated. While the functional validation of NDD-associated genes has predominantly been carried out using mouse models, the significant differences in brain structure and gene function between mice and humans have limited the effectiveness of mouse models in exploring the underlying mechanisms of NDD. Therefore, it is important to establish alternative animal models that are more evolutionarily aligned with humans. Results In this study, we employed CRISPR/Cas9 and somatic cell nuclear transplantation technologies to successfully generate a knockout miniature pig model of the MIR137 gene, which encodes the neuropsychiatric disorder-associated microRNA miR-137. The homozygous knockout of MIR137 (MIR137 –/– ) effectively suppressed the expression of mature miR-137 and led to the birth of stillborn or short-lived piglets. Transcriptomic analysis revealed significant changes in genes associated with neurodevelopment and synaptic signaling in the brains of MIR137 –/– miniature pig, mirroring findings from human ASD transcriptomic data. In comparison to miR-137-deficient mouse and human induced pluripotent stem cell (hiPSC)-derived neuron models, the miniature pig model exhibited more consistent changes in critical neuronal genes relevant to humans following the loss of miR-137. Furthermore, a comparative analysis identified differentially expressed genes associated with ASD and ID risk genes in both miniature pig and hiPSC-derived neurons. Notably, human-specific miR-137 targets, such as CAMK2A, known to be linked to cognitive impairments and NDD, exhibited dysregulation in MIR137 –/– miniature pigs. These findings suggest that the loss of miR-137 in miniature pigs affects genes crucial for neurodevelopment, potentially contributing to the development of NDD. Conclusions Our study highlights the impact of miR-137 loss on critical genes involved in neurodevelopment and related disorders in MIR137 –/– miniature pigs. It establishes the miniature pig model as a valuable tool for investigating neurodevelopmental disorders, providing valuable insights for potential applications in human research.

Serine/arginine-rich splicing factor 3 (SRSF3), the smallest member of the SR protein family, serves multiple roles in RNA processing, including splicing, translation, and stability. Recent studies have shown that SRSF3 is implicated in several inflammatory diseases. However, its impact on macrophage inflammation remains unclear. Herein, we determined the expression of SRSF3 in inflammatory macrophages and found that the level of SRSF3 was increased in macrophages within atherosclerotic plaques, as well as in RAW-264.7 macrophages stimulated by lipopolysaccharides. Moreover, the downregulation of SRSF3 suppressed the levels of inflammatory cytokines by deactivating the nuclear factor κB (NFκB) pathway. Furthermore, the alternative splicing of myeloid differentiation protein 2 (MD2), a co-receptor of toll-like receptor 4 (TLR4), is regulated by SRSF3. The depletion of SRSF3 increased the level of the shorter MD2B splicing variants, which contributed to inflammatory inhibition in macrophages. In conclusion, our findings imply that SRSF3 regulates lipopolysaccharide-stimulated inflammation, in part by controlling the alternative splicing of MD2 mRNA in macrophages.

Abstract Rapid tool wear conditions during the manufacturing process are crucial for the enhancement of product quality. As an extension of our recent works, in this research, a generic in-situ tool wear condition monitoring during the end milling process based on dynamic mode and abnormal evaluation is proposed. With the engagement of dynamic mode decomposition, the real-time response of the sensing physical quantity during the end milling process can be predicted. Besides, by constructing the graph structure of the time series and calculating the difference between the predicted signal and the real-time signal, the anomaly can be acquired. Meanwhile, the tool wear state during the end milling process can be successfully evaluated. The proposed method is validated in milling tool wear experiments and received positive results (the mean relative error is recorded as 0.0507). The research, therefore, paves a new way to realize the in-situ tool wear condition monitoring.

Abstract Airway remodelling in lung diseases can be treated by inhibiting excessive smooth muscle cell proliferation. Zedoarondiol (Zed) is a natural compound isolated from the Chinese herb Curcuma longa. The caveolin-1 (CAV-1) is widely expressed in lung cells and plays a key role in platelet-derived growth factor (PDGF) signalling and cell proliferation. This study aims to investigate the effect of Zed on human bronchial smooth muscle cell (HBSMC) proliferation and explore its potential molecular mechanisms. We assessed the effect of Zed on the proliferation of PDGF-stimulated HBSMCs and performed proteomic analysis to identify potential molecular targets and pathways. CAV1 siRNA was used to validate our findings in vitro. In PDGF-stimulated HBSMCs, Zed significantly inhibited excessive proliferation of HBSMCs. Proteomic analysis of zedoarondiol-treated HBSMCs revealed significant enrichment of differentially expressed proteins in cell proliferation-related pathways and biological processes. Zed inhibition of HBSMC proliferation was associated with upregulation of CAV1, regulation of the CAV-1/PDGF pathway and inhibition of MAPK and PI3K/AKT signalling pathway activation. Treatment of HBSMCs with CAV1 siRNA partly reversed the inhibitory effect of Zed on HBSMC proliferation. Thus, this study reveals that zedoarondiol potently inhibits HBSMC proliferation by upregulating CAV-1 expression, highlighting its potential value in airway remodelling and related diseases.

Abstract Hepatocellular carcinoma (HCC) is a common malignancy with poor survival and requires long-term follow-up. Hence, we collected information on patients with Primary Hepatocellular Carcinoma in the United States from the Surveillance, Epidemiology, and EndResults (SEER) database. We used this information to establish a deep learning with a multilayer neural network (the NMTLR model) for predicting the survival rate of patients with Primary Hepatocellular Carcinoma. HCC patients pathologically diagnosed between January 2011 and December 2015 in the SEER (Surveillance, Epidemiology, and End Results) database of the National Cancer Institute of the United States were selected as study subjects. We utilized two deep learning-based algorithms (DeepSurv and Neural Multi-Task Logistic Regression [NMTLR]) and a machine learning-based algorithm (Random Survival Forest [RSF]) for model training. A multivariable Cox Proportional Hazards (CoxPH) model was also constructed for comparison. The dataset was randomly divided into a training set and a test set in a 7:3 ratio. The training dataset underwent hyperparameter tuning through 1000 iterations of random search and fivefold cross-validation. Model performance was assessed using the concordance index (C-index), Brier score, and Integrated Brier Score (IBS). The accuracy of predicting 1-year, 3-year, and 5-year survival rates was evaluated using Receiver Operating Characteristic (ROC) curves, calibration plots, and Area Under the Curve (AUC). The primary outcomes were the 1-year, 3-year, and 5-year overall survival rates. Models were developed using DeepSurv, NMTLR, RSF, and Cox Proportional Hazards regression. Model differentiation was evaluated using the C-index, calibration with concordance plots, and risk stratification capability with the log-rank test. The study included 2197 HCC patients, randomly divided into a training cohort (70%, n = 1537) and a testing cohort (30%, n = 660). Clinical characteristics between the two cohorts showed no significant statistical difference (p > 0.05). The deep learning models outperformed both RSF and CoxPH models, with C-indices of 0.735 (NMTLR) and 0.731 (DeepSurv) in the test dataset. The NMTLR model demonstrated enhanced accuracy and well-calibrated survival estimates, achieving an Area Under the Curve (AUC) of 0.824 for 1-year survival predictions, 0.813 for 3-year, and 0.803 for 5-year survival rates. This model's superior calibration and discriminative ability enhance its utility for clinical prognostication in Primary Hepatocellular Carcinoma. We deployed the NMTLR model as a web application for clinical practice. The NMTLR model have potential advantages over traditional linear models in prognostic assessment and treatment recommendations. This novel analytical approach may provide reliable information on individual survival and treatment recommendations for patients with primary liver cancer.

ABSTRACT Gene expression and proper downstream cellular functions upon facing environmental shifts depend on the combined and cooperative regulation of genetic networks. Here, we identified cAMP receptor protein (CRP) as a master regulator of (p)ppGpp (guanosine tetra- and penta-phosphate) homeostasis. Via CRP-mediated direct transcriptional regulation of the (p)ppGpp synthetase/hydrolase RelA and SpoT, cAMP-CRP stimulates pervasive accumulation of (p)ppGpp under glucose-limiting conditions. Notably, CRP exerts a nonclassical property as a translational regulator through YfiQ-dependent acetylation of ribosome protein S1 at K247, which further enhances the translation of RelA, SpoT, and CRP itself. From a synthetic biology perspective, this self-activating feedback loop for (p)ppGpp synthesis highlights the function of CRP-mediated dual enhancement (CMDE) in controlling bacterial gene expression, which enables stable activation of genetic circuits. CMDE applied in synthetic circuits leads to a stable increase in p-coumaric acid, cinnamic acid, and pinosylvin production. Our findings showed that CRP-mediated dual circuits for (p)ppGpp regulation enable robust activation that could address bioproduction and other biotechnological needs.IMPORTANCETranscriptional–translational coordination is fundamental for rapid and efficient gene expression in most bacteria. Here, we uncovered the roles of cAMP-CRP in this process. We found that CRP distinctly increases RelA and SpoT transcription and translation, and that acetylation of S1 at K247 accelerates the self-activation of the leading CRP under glucose-limiting conditions. We further found that elevated (p)ppGpp significantly impedes the formation of the cAMP-CRP complex, an active form responsible for transcriptional activation. A model was created in which cAMP-CRP and (p)ppGpp cooperate to dynamically modulate the efficiency of transcriptional–translational coordination responses to stress. More broadly, productive activation in synthetic circuits was achieved through the application of CRP-mediated dual enhancement (CMDE), promising to inspire new approaches for the development of cell-based biotechnologies.

Abstract Dual‐mode readout platforms with colorimetric and electrochemiluminescence (ECL) signal enhancement are proposed for the ultrasensitive and flexible detection of the monkeypox virus (MPXV) in different scenes. A new nanotag, Ru@U6‐Ru/Pt NPs is constructed for dual‐mode platforms by integrating double‐layered ECL luminophores and the nanozyme using Zr‐MOF (UiO‐66‐NH2) as the carrier, which not only generates enhanced ECL and colorimetric signals but also provide greater stability than that of commonly used nanotags. Dual‐mode platforms are used within 15 min from the “sample in” to the “result out” steps, without nucleic acid amplification. The colorimetric mode allows the screening of MPXV with the visual limit of detection (vLOD) of 0.1 pM (6 × 108 copies µL−1) and the ECL mode supports quantitative detection of MPXV with an LOD as low as 10 aM (6 copies·µL−1), resulting in a broad sensing range of 60 to 3 × 1011 copies·µL−1 (10 orders of magnitude). Validation is conducted using 50 clinical samples, which is 100% concordant to those of quantitative polymerase chain reaction (qPCR), indicating that Ru@U6‐Ru/Pt NPs‐based dual‐mode sensing platforms showed great promise as rapid, sensitive, and accurate tools for diagnosis of the nucleic acid of MPXV and other infectious pathogens.

This study assessed the impacts of monosodium glutamate (MSG) on the growth performance, feed utilization, feed intake, and appetite regulation of Chinese mitten crab, Eriocheir sinensis. A total of 240 juvenile crabs (9.16 ± 0.21 g) were assigned to six experimental diets supplemented with MSG at 0 %, 0.20 %, 0.39 %, 0.59 %, 0.78 % and 0.98 %. The results demonstrated that 0.59 % MSG supplementation significantly enhanced the weight gain rate (WGR), specific growth rate (SGR), and feed utilization of juvenile E. sinensis by increasing feed intake (FI) (p < 0.05). Moreover, dietary moderate MSG improved the mid-intestine morphology, such as height of microvillus (HMV), width of microvillus (WMV), and thickness of muscularis (TM). The qRT-PCR analysis demonstrated that the mRNA expression levels of the appetite-stimulating neural signals agouti related protein (agrp) and ghrelin were increased significantly by dietary moderate MSG (p < 0.05). Conversely, the mRNA levels of protein kinase B (akt), target of rapamycin (tor) and 4E-binding protein (4e-bp), as well as appetite-suppressing neural signals pro-opiomelanocortin (pomc), corticotropin-releasing factor (crf) and peptide yy (pyy) were significantly down-regulated (p < 0.05). The two-slope broken-line regression analysis of SGR in relation to dietary MSG levels suggested that the optimum dietary MSG level for juvenile E. sinensis was 5.6 g/kg. Collectively, MSG may potentially stimulate or suppress the appetite regulation neural signals/hormones, thereby modulating the feeding behavior of E. sinensis.

The antitumor activity of a fermented juice (called Shaduojin, SDJ) made from sea buckthorn, raspberry, etc. was investigated using CT26 bearing mice. The results showed a dose-dependent inhibition of tumor growth in the SDJ groups compared to the model group. The number of CD8+ T and dendritic cells were increased while the Treg cells and monocytes was decreased in both the tumor and spleen in the SDJ groups. The TNF-α and INF-γ increased and the IL-1β, IL-6, and IL-10 decreased in the SDJ groups. Additionally, there was an increase in the abundance of beneficial bacteria (Firmicutes, Coildextribacter, and Lachnospiraceae) which contribute to intestinal health and produce short-chain fatty acids (SCFAs). On the other hand, harmful bacteria (Muribaculaceae and uncultured Bacteroidales) decreased. The SCFA content in the intestine also increased in the SDJ groups. Therefore, it has been showed that SDJ may elicit its effect on preventing colorectal cancer by regulating the immune system and gut microbiota.

This study aimed to modify plant protein mixture to improve their functionality and digestibility by limited hydrolysis. Soy protein isolate and corn zein were mixed at the ratio of 5:1 (w/w), followed by limited hydrolysis using papain from 15 to 30 min. The structural characteristics, in vitro digestibility, and functional properties were evaluated. Also, DPPH radical scavenging activity was determined. The results indicated that the molecular weight of different modified samples was largely reduced by limited hydrolysis, and the proportion of random coil was significantly increased. Furthermore, the solubility, foaming, emulsifying and water-holding capacity of hydrolyzed protein mixture were significantly improved, which were close to those of whey protein isolate. In vitro digestibility after 30-min limited hydrolysis was remarkably elevated. In addition, the hydrolyzed protein mixture exhibited a higher antioxidant activity than those of untreated proteins. Overall, limited hydrolysis of protein mixture led to improved digestibility, functionality and antioxidant activity.

Introduction: People in low socioeconomic circumstances are more susceptible to dyslipidemia and cardiovascular disease than those living in more affluent populations. Limited healthcare access and low preventive care uptake widen health inequalities. Understanding how primary care can better serve socioeconomically disadvantaged communities is urgently needed. Aim: To explore lipid management delivery in socioeconomically disadvantaged areas and identify barriers and enablers for lipid optimization for socioeconomically disadvantaged populations. Method: Individual semi-structured remote interviews with clinicians, purposively recruited from primary care practices serving extremely socioeconomically disadvantaged communities in Northern England, UK, who were involved in the delivery and organization of lipid management. Interviews were recorded, transcribed, and analyzed thematically following framework analysis. Results: Fifteen interviews were undertaken. Five themes emerged: complex and multimorbid patients with competing priorities, limited access and follow-up to supporting services, being flexible and working beyond guidelines, high workload with inadequate staff support, and the need for care integrity and sustainable support. Conclusion: The findings of this study have been fed back to the delivery of the national program to improve cardiovascular health. Socioeconomically disadvantaged communities have complex health needs posing risks of multimorbidity but living with low health literacy, competing demands upon time, and financial constraints. Clinicians are willing to adapt services but a lack of guidance for care and funded services remains a significant barrier to targeted service delivery. Research is needed to inform the effectiveness and acceptability of interventions for lipid management tailored for those experiencing low socioeconomic disadvantage.

Abstract Exploring the level of intraspecific diversity in taxa experienced radiation is helpful to understanding speciation and biodiversity assembly. Gentiana section Chondrophyllae sensu lato encompasses more than 180 species and occupies more a half of species in the genus. In this study, we collected samples across the range of three species (Gentiana aristata, G. crassuloides and G. haynaldii) in section Chondrophyllae s.l., and recovered the intra‐species variation by comparing with closely related taxon. Using 25 newly sequenced plastid genomes together with previously published data, we compared structural differences, quantified the variations in plastome size, and measured nucleotide diversity in various regions. Our results showed that the plastome size variation in the three Chondrophyllae species ranged from 285 to 628 bp, and the size variation in LSC, IR and SSC ranged from 236 to 898 bp, 52 to 393 bp and 135 to 356 bp, respectively. Nucleotide diversity of plastome or any of the four regions was much higher than the control species. The average nucleotide diversity in plastomes of the three species ranged from 0.0010 to 0.0023 in protein coding genes, and from 0.0023 to 0.0061 in intergenic regions. More repeat sequence variations were detected within the three Chondrophyllae species than the control species. Various plastid sequence matrixes resulted in different backbone topology in two target species, showed uncertainty in phylogenetic relationship based inference. In conclusion, our results recovered that species of G. section Chondrophyllae s.l. has high intraspecific plastome variation, and provided insights into the radiation in this speciose lineage.

Background Social welfare legal needs (matters of daily life, such as finances, housing and employment with legal rights, entitlements or protections) are prevalent towards end of life, creating significant difficulties for both patients and carers. Most people do not know where to go, although a range of services provide advice and support for addressing social welfare legal problems. Navigating this complex and fragmented system across health, social care and social welfare legal support is very challenging. Healthcare professionals are often the first contact for social welfare legal needs, although these are often overlooked and their impact on health and well-being unrecognised. Interprofessional learning can increase awareness of social welfare legal needs and build connections between service providers, offering a more holistic and cohesive multiagency response to the complex needs around end of life. The aim of the research was to co-create a robust foundation for cross-agency research investigating the impact of interprofessional learning on social welfare legal needs towards end of life in the North East England region. Objectives Convene a research partnership group across academics, multiagency service providers and members of the public with lived experience. Consider and agree key issues for successful place-based multiagency research in this area. Co-create a complexity-appropriate research proposal with interprofessional learning as an intervention. Methods A series of research activities was implemented to convene a multiagency partnership group and consider the key issues for successful place-based multiagency research. Data were collected from two online workshops, an optional reflective workbook, and a modified Delphi technique. Initial participants were selectively recruited from our established stakeholder and patient and public involvement groups. Increasing diversity of the partnership continued throughout the project, using contacts provided by group members. Representation of services supporting underserved groups was a priority. Results All invited participants were recruited to the partnership, although contribution to research activities was variable. The partnership bridged knowledge gaps between services and united diverse perspectives, expertise and experience. A greater understanding of the barriers and opportunities for place-based multiagency working was generated, such as considering the importance of language in facilitating collaboration and responding to concerns around capacity. A non-hierarchical partnership was meaningful, with both personal and professional insights viewed as equally important. Facilitators to engagement with interprofessional learning were identified including the need for leadership endorsement. A non-traditional, mixed-method approach to interprofessional learning evaluation was favoured, with both qualitative and quantitative measures at three levels: patient and carer, professional learners and organisations. Important outcomes included raising awareness, connectedness and space to reflect. Limitations The partnership group expanded throughout the course of the project. While this extended diversity, variable participation hindered depth of discussion, with participants engaging at different points and with different understanding levels of the project. Supplementary materials provided some mitigation. Capacity and funding constraints limited engagement for some participants. Conclusions Convening a multiagency partnership generated insights into the benefits, barriers and facilitators to research co-design and potential measures of success of interprofessional learning. Future work Learning from this project has informed a complexity-appropriate research proposal to evaluate the impact of interprofessional learning as an intervention across different stakeholders. Funding This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme as award number NIHR135276. Plain language summary Social welfare legal issues, such as unsuitable housing, job difficulties and money concerns, are common in the last 12 months of a person’s life and they affect carers too. Getting the right help can be difficult as it is hard to know where to go. Organisations and services often work separately from each other. Healthcare professionals are often the first contact for social welfare legal needs, but they may not be able to provide the required support. Interprofessional learning brings professionals together to learn from each other and connect services better. We think this will make it easier for people to get the help they need when the same is required. We set up a group of professionals and four people with personal experience. This partnership group started with people and organisations we knew already but more joined during the project. By the end, 37 different services, representing a range of health, advice and community services, had joined the research group. All services had experience of social welfare legal issues in the last 12 months of life. The group discussed running research together and how interprofessional learning could be tested in our next research project. Research activities were: two online meetings to discuss key questions a workbook which gave time to think about the questions we were asking a survey which asked participants their views about measuring success of interprofessional learning. Group members brought a variety of experiences and opinions. Some had difficulty taking part, mainly because of time. We learnt that professional and personal experiences are as important as each other and that it is important to avoid jargon. Testing if interprofessional learning makes a difference needs to look at people using services, professionals and organisations. We have written a funding application, based on what we have learnt in this project.

Objectives This study addressed two research questions: What factors do doctors in training describe as influencing their choices to apply (or not apply) for specialty training during their Foundation Year 2? Which of these factors are specific to the context of the COVID-19 pandemic, and the unique experiences of the cohort of doctors who qualified early during the pandemic?Design Sequential explanatory mixed methods study: Quantitative survey. Qualitative semistructured interviews. Quantitative data were analysed with logistic regression. Qualitative data were analysed using reflexive thematic analysis.Setting UK-wide.Participants Junior doctors who graduated medical school in 2020. Survey: 320 participants (22% of those contacted). 68% (n=219) were female, 60% (n=192) under 25 and 35% (n=112) 25–30. 72% (n=230) were white, 18% (n=58) Asian and 3% (n=10) black. Interviews: 20 participants, 10 had applied for specialty training, 10 had not.Results A minority of respondents had applied for specialty training to start in 2022 (114, 36%). While burnout varied, with 15% indicating high burnout, this was not associated with the decision to apply. This decision was predicted by having taken time off due to work-related stress. Those who had not taken time off were 2.4 times more likely to have applied for specialty training (OR=2.43, 95% CI 1.20 to 5.34). Interviews found reasons for not applying included wanting to ‘step off the treadmill’ of training; perceptions of training pathways as inflexible, impacting well-being; and disillusionment with the community and vocation of healthcare, based, in part, on their experiences working through COVID-19.Conclusions Participants infrequently cited factors specific to the pandemic had impacted their decision-making but spoke more broadly about challenges associated with increasing pressure on the health service and an eroded sense of vocation and community.

During freeze–thaw cycling, aggregates undergo a dynamic change in breakdown–formation (turnover), however, how the turnover occurs between aggregates of various particle sizes is not clear. To clarify the influence of freeze–thaw cycling on the dynamic changes in the particle size of soil aggregates, soil aggregates from the Black Soil Region of Northeast China were selected as the research objects. The study conducted in situ dynamic monitoring experiments, innovatively applying the rare earth oxide (REO) tracer method to natural conditions of freeze–thaw cycles (autumn freeze–thaw period, freezing period, and spring freeze–thaw period), accurately tracking the turnover paths and quantifying the turnover rates between aggregates of various particle sizes. The results revealed that the total value of the formation paths of the 2–5 mm aggregates and 0.25–2 mm aggregates increased during the autumn freeze–thaw period. The number of freeze–thaw cycles and accumulated snowfall were significantly positively correlated with aggregate stability, with an increase in the number of freeze–thaw cycles and accumulated snowfall resulting in an increase in the proportion of aggregates > 0.25 mm, which improved aggregate stability. In addition, the total value of the breakdown path of macro-aggregates increased during the spring freeze–thaw cycling period. Soil moisture was significantly negatively correlated with aggregate stability, with increased soil moisture resulting in a decrease in the percentage of aggregates > 0.25 mm, which resulted in a decrease in aggregate stability. The study can provide a reference understanding for the effects of freeze–thaw cycles on the structure of black soil and provide a theoretical basis for improving the quality of arable land.

Abstract Objective Evaluation of the predictive value of one-stop energy spectrum and perfusion CT parameters for microvessel density (MVD) in colorectal cancer cancer foci. Methods Clinical and CT data of 82 patients with colorectal cancer confirmed by preoperative colonoscopy or surgical pathology in our hospital from September 2019 to November 2022 were collected and analyzed retrospectively. Energy spectrum CT images were measured using the Protocols general module of the GSI Viewer software of the GE AW 4.7 post-processing workstation to measure the CT values of the arterial and venous phase lesions and the neighboring normal intestinal wall in a single energy range of 40 kev∼140 kev, and the slopes of the energy spectrum curves (λ) were calculated between 40 kev-90 kev; Iodine concentration (IC), Water concentration (WC), Effective-Z (Eff-Z) and Normalized iodine concentration (NIC) were measured by placing a region of interest (ROI) on the iodine concentration map and water concentration map at the lesion and adjacent to the normal intestinal wall.Perfusion CT images were scanned continuously and dynamically using GSI Perfusion software and analyzed by applying CT Perfusion 4.0 software.Blood volume (BV), blood flow (BF), surface permeability (PS), time to peak (TTP), and mean transit time (MTT) were measured respectively in the lesion and adjacent normal colorectal wall. Based on the pathological findings, the tumors were divided into a low MVD group (MVD

Serine/arginine-rich splicing factors (SRSFs), part of the serine/arginine-rich (SR) protein family, play a crucial role in precursor RNA splicing. Abnormal expression of SRSFs in tumors can disrupt normal RNA splicing, contributing to tumor progression. Notably, SRSF7 has been found to be upregulated in hepatocellular carcinoma (HCC), yet its specific role and molecular mechanisms in HCC pathogenesis are not fully understood. We investigated the expression and prognostic significance of SRSF7 in HCC using bioinformatics database analysis. In HepG2 cells, the expressions of SRSF7 and glycolytic enzymes were analyzed using qRT-PCR, and Western blot. Glucose uptake and lactate production were quantified using relevant reagent kits. Additionally, cell proliferation, clonogenicity, invasion, and apoptosis were evaluated using MTS assay, clonal formation assay, Transwell assay, and mitochondrial membrane potential assay, respectively. This study demonstrated significant overexpression of SRSF7 in HCC tissue, correlating with poor prognosis. Knockdown of SRSF7 in HepG2 cells resulted in inhibited proliferation, clonogenicity, and invasion, while apoptosis was enhanced. This knockdown also decreased glucose uptake and lactate production, along with a reduction in the expression of glucose transporter 1 (GLUT1) and lactate dehydrogenase A (LDHA). Furthermore, SRSF7 downregulation increased the pyruvate kinase muscle 1 (PKM1)/PKM2 ratio. The glycolytic boost due to PKM2 overexpression partially counteracted the effects of SRSF7 silencing on HepG2 cell growth. The knockdown of SRSF7 impairs aerobic glycolysis and growth in HepG2 cells by downregulating PKM2 expression.

Abstract Background In this study, we sought to quantify the influence of vertical control assisted by a temporary anchorage device (TAD) on orthodontic treatment efficacy for skeletal class II patients with a hyperdivergent facial type and probe into the critical factors of profile improvement. Methods A total of 36 adult patients with skeletal class II and a hyperdivergent facial type were included in this retrospective case–control study. To exclude the effect of sagittal anchorage reinforcement, the patients were divided into two groups: a maxillary maximum anchorage (MMA) group (N = 17), in which TADs were only used to help with anterior tooth retraction, and the MMA with vertical control (MMA + VC) group (N = 19), for which TADs were also used to intrude the maxillary molars and incisors. The treatment outcome was evaluated using dental, skeletal, and soft-tissue-related parameters via a cephalometric analysis and cast superimposition. Results A significant decrease in ANB (P

Abstract c-di-AMP is an essential and widespread nucleotide second messenger in bacterial signaling. For most c-di-AMP synthesizing organisms, c-di-AMP homeostasis and the molecular mechanisms pertaining to its signal transduction are of great concern. Here we show that c-di-AMP binds the N-acetylglucosamine (GlcNAc)-sensing regulator DasR, indicating a direct link between c-di-AMP and GlcNAc signaling. Beyond its foundational role in cell-surface structure, GlcNAc is attractive as a major nutrient and messenger molecule regulating multiple cellular processes from bacteria to humans. We show that increased c-di-AMP levels allosterically activate DasR as a master repressor of GlcNAc utilization, causing the shutdown of the DasR-mediated GlcNAc signaling cascade and leading to a consistent enhancement in the developmental transition and antibiotic production in Saccharopolyspora erythraea. The expression of disA, encoding diadenylate cyclase, is directly repressed by the regulator DasR in response to GlcNAc signaling, thus forming a self-sustaining transcriptional feedback loop for c-di-AMP synthesis. These findings shed light on the allosteric regulation by c-di-AMP, which appears to play a prominent role in global signal integration and c-di-AMP homeostasis in bacteria and is likely widespread in streptomycetes that produce c-di-AMP.

Abstract Background Plasma microRNAs act as biomarkers for predicting and diagnosing diseases. Reliable non-invasive biomarkers for biochemical pregnancy loss have not been established. We aim to analyze the dynamic microRNA profiles during the peri-implantation period and investigate if plasma microRNAs could be non-invasive biomarkers predicting BPL. Methods In this study, we collected plasma samples from patients undergoing embryo transfer (ET) on ET day (ET0), 11 days after ET (ET11), and 14 days after ET (ET14). Patients were divided into the NP (negative pregnancy), BPL (biochemical pregnancy loss), and CP (clinical pregnancy) groups according to serum hCG levels at day11~14 and ultrasound at day28~35 following ET. MicroRNA profiles at different time-points were detected by miRNA-sequencing. We analyzed plasma microRNA signatures for BPL at the peri-implantation stage, we characterized the dynamic microRNA changes during the implantation period, constructed a microRNA co-expression network, and established predictive models for BPL. Finally, the sequencing results were confirmed by Taqman RT-qPCR. Results BPL patients have distinct plasma microRNA profiles compared to CP patients at multiple time-points during the peri-implantation period. Machine learning models revealed that plasma microRNAs could predict BPL. RT-qPCR confirmed that miR-181a-2-3p, miR-9-5p, miR-150-3p, miR-150-5p, and miR-98-5p, miR-363-3p were significantly differentially expressed between patients with different reproductive outcomes. Conclusion Our study highlights the non-invasive value of plasma microRNAs in predicting BPL.

Abstract The increasing global aging population has led to a continual rise in the prevalence of bone and joint diseases, posing challenges to both the quality of life for patients and healthcare resources. Type II collagen, a pivotal protein for sustaining joint function, has gained substantial attention in recent years. The oral administration of undenatured type II collagen (UC-II) has demonstrated noteworthy advancements in tackling bone and joint diseases. This article presents a comprehensive review of the structure and extraction methods of UC-II, discusses the relationship between UC-II and arthritis, and thoroughly examines its therapeutic role and potential mechanisms in the treatment process. In addition, future perspectives for clinical application of UC-II are discussed. It was found that the oral administration of UC-II, through induction of oral tolerance mechanisms, exhibits promise in alleviating joint inflammation and pain in patients with osteoarthritis (OA) and rheumatoid arthritis (RA). This method can significantly ameliorate joint inflammation and pain, with high patient acceptance and minimal side effects, demonstrating its potential as a well-tolerated treatment option for joint diseases. Graphical Abstract

The influences of simultaneous precipitation of isothermal ω and O′ on deformation mechanisms and mechanical properties of near β Ti alloy Ti-5Al-3Mo-3V-2Cr-2Zr-1Nb-1Fe with (α + β) hybrid structure are revealed. During continuous heating, the phase transformation sequence in this alloy is β + αp + ω-embryos + O′ → β + αp + ωiso + O′ → β + αp + ωiso + O′ + αs → β + αp + αs. Low-temperature heat treatments from 200 °C to 400 °C are carried out to develop such intermediate phases. Upon aging at 200 °C and 300 °C, the isothermal ω and O′ domains are continuously generated. In comparison with solution state, the deformation behaviors of aged samples are altered, and the yield stress and ductility are simultaneously increased. When aged at 200 °C, the yield strength is increased by 13.8 %, and fracture elongation is increased by 63.2 %. When aged at 300 °C, the yield strength is increased by 18.2 %, and preserves large ductility same to solution state. This is due to the development of isothermal ω and O′ domains suppress long-range stress induced martensitic transformation during loading, and the deformation mechanisms evolve into dislocations slipping gradually. When the aging temperature increases to 400 °C, α precipitation takes place leading to an obvious decrement in ductility. Upon loading the primary α can also accommodate partly the strains and relax local stress concentration. The results in this work clearly proves that better mechanical properties can be achieved through tailoring intermediate phases generation.

Abstract Objective The purpose of this study was to develop an individual survival prediction model based on multiple machine learning (ML) algorithms to predict survival probability for remnant gastric cancer (RGC). Methods Clinicopathologic data of 286 patients with RGC undergoing operation (radical resection and palliative resection) from a multi-institution database were enrolled and analyzed retrospectively. These individuals were split into training (80%) and test cohort (20%) by using random allocation. Nine commonly used ML methods were employed to construct survival prediction models. Algorithm performance was estimated by analyzing accuracy, precision, recall, F1-score, area under the receiver operating characteristic curve (AUC), confusion matrices, five-fold cross-validation, decision curve analysis (DCA), and calibration curve. The best model was selected through appropriate verification and validation and was suitably explained by the SHapley Additive exPlanations (SHAP) approach. Results Compared with the traditional methods, the RGC survival prediction models employing ML exhibited good performance. Except for the decision tree model, all other models performed well, with a mean ROC AUC above 0.7. The DCA findings suggest that the developed models have the potential to enhance clinical decision-making processes, thereby improving patient outcomes. The calibration curve reveals that all models except the decision tree model displayed commendable predictive performance. Through CatBoost-based modeling and SHAP analysis, the five-year survival probability is significantly influenced by several factors: the lymph node ratio (LNR), T stage, tumor size, resection margins, perineural invasion, and distant metastasis. Conclusions This study established predictive models for survival probability at five years in RGC patients based on ML algorithms which showed high accuracy and applicative value.

Abstract Demand-side flexible load resources, such as Electric Vehicles (EVs) and Air Conditioners (ACs), offer significant potential for enhancing flexibility in the power system, thereby promoting the full integration of renewable energy. To this end, this paper proposes an optimal allocation method for demand-side flexible resources to enhance renewable energy consumption. Firstly, the adjustable flexibility of these resources is modeled based on the generalized energy storage model. Secondly, we generate random scenarios for wind, solar, and load, considering variable correlations based on non-parametric probability predictions of random variables combined with Copula function sampling. Next, we establish the optimal allocation model for demand-side flexible resources, considering the simulated operation of these random scenarios. Finally, we optimize the demand-side resource transformation plan year by year based on the growth trend forecast results of renewable energy installed capacity in Jiangsu Province from 2025 to 2031.

Intratumoral microbiota has become research hotspots, and emerges as a non-negligent new component of tumor microenvironments (TME), due to its powerful influence on tumor initiation, metastasis, immunosurveillance and prognosis despite in low-biomass. The accumulations of microbes, and their related components and metabolites within tumor tissues, endow TME with additional pluralistic features which are distinct from the conventional one. Therefore, it's definitely necessary to comprehensively delineate the sophisticated landscapes of tumor microbe microenvironment, as well as their functions and related underlying mechanisms. Herein, in this review, we focused on the fields of tumor microbe microenvironment, including the heterogeneity of intratumor microbiota in different types of tumors, the controversial roles of intratumoral microbiota, the basic features of tumor microbe microenvironment (i.e., pathogen-associated molecular patterns (PAMPs), typical microbial metabolites, autophagy, inflammation, multi-faceted immunomodulation and chemoresistance), as well as the multidisciplinary approach-based intervention of tumor microbiome for cancer therapy by applying wild-type or engineered live microbes, microbiota metabolites, antibiotics, synthetic biology and rationally designed biomaterials. We hope our work will provide valuable insight to deeply understand the interplay of cancer-immune-microbial, and facilitate the development of microbes-based tumor-specific treatments.

Objective The purpose of this study was to explore the effect of sodium salicylate (SS) on semen preservation and metabolic regulation in goats. Methods Under the condition of low temperature, SS was added to goat semen diluent to detect goat sperm motility, plasma membrane, acrosome, antioxidant capacity, mitochondrial membrane potential (MMP) and metabonomics. Results The results show that at the 8th day of low-temperature storage, the sperm motility of the 20 μM SS group was 66.64%, and the integrity rates of the plasma membrane and acrosome were both above 60%, significantly higher than those of the other groups. The activities of catalase and superoxide dismutase in the sperm of the 20 μM SS group were significantly higher than those of the control group, the contents of reactive oxygen species and malondialdehyde were significantly lower than those in the control group, the MMP was significantly higher than that in the control group, and the contents of Ca2+ and total cholesterol were significantly higher than those in the control group. Through metabonomics analysis, there were significant metabolic differences between the control group and the 20 μM SS group. Twenty of the most significant metabolic markers were screened, mainly involving five metabolic pathways, of which nicotinic acid and nicotinamide metabolic pathways were the most significant. Conclusion The results indicate that SS can effectively improve the low-temperature preservation quality of goat sperm.

Since software defined network (SDN) was more vulnerable to network attacks than traditional networks, the research progress of abnormal traffic detection for software defined network in recent years from the technical principle and architecture characteristics was summarized, the possible organizational forms of network attacks on SDN were analyzed, and the characteristics, advantages, and disadvantages of current technologies related to abnormal traffic detection, abnormal traffic traceability, and abnormal traffic mitigation were discussed.The data sets commonly used in current research were compared and analyzed, and some general data preprocessing methods were sorted out.The research direction of abnormal traffic detection methods in the SDN environment in the future was summarized and prospected.The research results can guide the selection of adaptation methods in practical application requirements, and the problems and contradictions to be solved can guide subsequent research.

Abstract Hyperthermic intraperitoneal chemotherapy’s role in ovarian cancer remains controversial, hindered by limited understanding of hyperthermia-induced tumor cellular changes. This limits developing potent combinatory strategies anchored in hyperthermic intraperitoneal therapy (HIPET). Here, we perform a comprehensive multi-omics study on ovarian cancer cells under hyperthermia, unveiling a distinct molecular panorama, primarily characterized by rapid protein phosphorylation changes. Based on the phospho-signature, we pinpoint CDK1 kinase is hyperactivated during hyperthermia, influencing the global signaling landscape. We observe dynamic, reversible CDK1 activity, causing replication arrest and early mitotic entry post-hyperthermia. Subsequent drug screening shows WEE1 inhibition synergistically destroys cancer cells with hyperthermia. An in-house developed miniaturized device confirms hyperthermia and WEE1 inhibitor combination significantly reduces tumors in vivo. These findings offer additional insights into HIPET, detailing molecular mechanisms of hyperthermia and identifying precise drug combinations for targeted treatment. This research propels the concept of precise hyperthermic intraperitoneal therapy, highlighting its potential against ovarian cancer.

Abstract Background Deteriorations in eggshell and bone quality are major challenges in aged laying hens. This study compared the differences of eggshell quality, bone parameters and their correlations as well as uterine physiological characteristics and the bone remodeling processes of hens laying eggs of different eggshell breaking strength to explore the mechanism of eggshell and bone quality reduction and their interaction. A total of 240 74-week-old Hy-line Brown laying hens were selected and allocated to a high (HBS, 44.83 ± 1.31 N) or low (LBS, 24.43 ± 0.57 N) eggshell breaking strength group. Results A decreased thickness, weight and weight ratio of eggshells were observed in the LBS, accompanied with ultrastructural deterioration and total Ca reduction. Bone quality was negatively correlated with eggshell quality, marked with enhanced structures and increased components in the LBS. In the LBS, the mammillary knobs and effective layer grew slowly. At the initiation stage of eggshell calcification, a total of 130 differentially expressed genes (DEGs, 122 upregulated and 8 downregulated) were identified in the uterus of hens in the LBS relative to those in the HBS. These DEGs were relevant to apoptosis due to the cellular Ca overload. Higher values of p62 protein level, caspase-8 activity, Bax protein expression and lower values of Bcl protein expression and Bcl/Bax ratio were seen in the LBS. TUNEL assay and hematoxylin-eosin staining showed a significant increase in TUNEL-positive cells and tissue damages in the uterus of the LBS. Although few DEGs were identified at the growth stage, similar uterine tissue damages were also observed in the LBS. The expressions of runt-related transcription factor 2 and osteocalcin were upregulated in humeri of the LBS. Enlarged diameter and more structural damages of endocortical bones and decreased ash were observed in femurs of the HBS. Conclusion The lower eggshell breaking strength may be attributed to a declined Ca transport due to uterine tissue damages, which could affect eggshell calcification and lead to a weak ultrastructure. Impaired uterine Ca transport may result in reduced femoral bone resorption and increased humeral bone formation to maintain a higher mineral and bone quality in the LBS. Graphical Abstract