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Introduction At present, stroke has become the first cause of death and disability among Chinese adults. With the coming of the aging population in China, the disease burden brought by stroke will be increasingly aggravated. And stroke is a leading cause of disability. There is a golden plastic period after stroke, during which timely and safe intervention and rehabilitation therapy can effectively improve the disability status. However, there is still controversy about the duration of interventional rehabilitation after stroke. This study conducted a meta-analysis on the influence of intervention in early and late ischemic stroke rehabilitation. Method Chinese language databases such as CNKI, Wanfang, and VIP, and English language databases such as Embase, PubMed, Web of Science, and The Cochrane Library were searched, and RCT related to early and late rehabilitation of ischemic stroke from the establishment of the database to October 2023 was collected. Review Manager 5.4.1 was used for relevant analysis. The main outcomes were Barthel Index or Modified Barthel Index, Fugl-Meyer Assessment scale, NIHSS, China Stroke Scale. Standardized Mean Difference (SMD) was used as an effective indicator of continuity variables, and the estimated interval was expressed by 95% confidence interval (CI). Results A total of 1908 patients were included in 16 studies. The results showed that, compared with late rehabilitation, early rehabilitation improved clinical efficacy. Barthel Index or Modified Barthel Index score was [SMD = 1.40, 95%CI(1.16,1.63), p  < 0.001]; the score of Fugl-Meyer Assessment Scale was [SMD = 1.18, 95%Cl (0.85, 1.52), P  < 0.001]; the score of NIHSS was [SMD= -0.44, 95% CI(-0.65, -0.24), P  < 0.001]; the result of China Stroke Scale score was [SMD= -0.37, 95%CI(-0.56, -0.18), P  < 0.001]. Conclusion In comparison with late rehabilitation, early rehabilitation can significantly improve self-care abilities, daily activities, and neurological functions of ischemic stroke patients. Trial registration This meta-analysis has been registered with Prospero, and the registration number is CRD42022309911. The registration period is March 22, 2022.

Macrophage migration inhibitory factor (MIF) is expressed in a variety of cells and participates in important biological mechanisms. However, few studies have reported whether MIF is expressed in human Embryonic stem cells (ESCs) and its effect on human ESCs. Two human ESCs cell lines, H1 and H9 were used. The expression of MIF and its receptors CD74, CD44, CXCR2, CXCR4 and CXCR7 were detected by an immunofluorescence assay, RT-qPCR and western blotting, respectively. The autocrine level of MIF was measured via enzyme-linked immunosorbent assay. The interaction between MIF and its main receptor was investigated by co-immunoprecipitation and confocal immunofluorescence microscopy. Finally, the effect of MIF on the proliferation and survival of human ESCs was preliminarily explored by incubating cells with exogenous MIF, MIF competitive ligand CXCL12 and MIF classic inhibitor ISO-1. We reported that MIF was highly expressed in H1 and H9 human ESCs. MIF was positively expressed in the cytoplasm, cell membrane and culture medium. Several surprising results emerge. The autosecreted concentration of MIF was 22 ng/mL, which was significantly higher than 2 ng/mL-6 ng/mL in normal human serum, and this was independent of cell culture time and cell number. Human ESCs mainly expressed the MIF receptors CXCR2 and CXCR7 rather than the classical receptor CD74. The protein receptor that interacts with MIF on human embryonic stem cells is CXCR7, and no evidence of interaction with CXCR2 was found. We found no evidence that MIF supports the proliferation and survival of human embryonic stem cells. In conclusion, we first found that MIF was highly expressed in human ESCs and at the same time highly expressed in associated receptors, suggesting that MIF mainly acts in an autocrine form in human ESCs.

Background: Ischemic stroke (IS) is the leading cause of mortality worldwide. Herein, we aimed to identify novel biomarkers and explore the role of C-type lectin domain family 7 member A (CLEC7A) in IS. Methods: Differentially expressed genes (DEGs) were screened using the GSE106680, GSE97537, and GSE61616 datasets, and hub genes were identified through construction of protein-protein interaction networks. An IS model was established by middle cerebral artery occlusion and reperfusion (MCAO/R). Neural function was assessed using triphenyl tetrazolium chloride, hematoxylin-eosin, and terminal deoxynucleotidyl transferase-mediated nick-end labeling. A cell counting kit was used to detect cell viability following oxygen-glucose deprivation/reperfusion (OGD/R). Inflammatory factors were detected using enzyme-linked immunosorbent assay. The mRNA and protein expression levels were detected using reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. Results: Fc fragment of Immunoglobulin G (IgG) receptor IIIa (FCGR3A), Fc fragment of Immunoglobulin E (IgE) receptor Ig (FCER1G), Complement component 5a receptor 1 (C5AR1), CLEC7A, Plasminogen activator, urokinase (PLAU), and C-C motif chemokine ligand 6 (CCL6) were identified as important hub genes, from which CLEC7A was selected as the primary subject of this study. The activation of microglia and pyroptosis were observed in MCAO/R model with increased levels of interleukin (IL)-1β, IL-18, tumor necrosis factor-α, and lactate dehydrogenase. CLEC7A knockdown was found to promote cell viability in BV2 cells and inhibiting pyroptosis in HT22 cells. CLEC7A knockdown in microglia also decreased infarct volume and neurological deficit scores, and alleviated injury and neuronal apoptosis in IS rats. CLEC7A knockdown inhibited pyroptosis and microglial activation in the MCAO/R model. A pyroptosis activator reversed the effect of CLEC7A knockdown on the viability of OGD/R-treated HT22 cells. Conclusion: CLEC7A is a promising biomarker of IS. CLEC7A knockdown alleviates IS by inhibiting pyroptosis and microglial activation.

The environmental perception capability of intelligent ships is essential for enhancing maritime navigation safety and advancing shipping intelligence. Image caption generation technology plays a pivotal role in this context by converting visual information into structured semantic descriptions. However, existing general purpose models often struggle to perform effectively in complex maritime environments due to limitations in visual feature extraction and semantic modeling. To address these challenges, this study proposes a transformer dual-stream information (TDSI) model. The proposed model uses a Swin-transformer to extract grid features and combines them with fine-grained scene semantics obtained via SegFormer. A dual-encoder structure independently encodes the grid and segmentation features, which are subsequently fused through a feature fusion module for implicit integration. A decoder with a cross-attention mechanism is then employed to generate descriptive captions for maritime images. Extensive experiments were conducted using the constructed maritime semantic segmentation and maritime image captioning datasets. The results demonstrate that the proposed TDSI model outperforms existing mainstream methods in terms of several evaluation metrics, including BLEU, METEOR, ROUGE, and CIDEr. These findings confirm the effectiveness of the TDSI model in enhancing image captioning performance in maritime environments.

Background Parkinson's disease (PD) is a common neurodegenerative disorder. Microglia‐mediated neuroinflammation has emerged as an involving mechanism at the initiation and development of PD. Activation of adenosine triphosphate (ATP)‐sensitive potassium (KATP) channels can protect dopaminergic neurons from damage. Sodium butyrate (NaB) shows anti‐inflammatory and neuroprotective effects in some animal models of brain injury and regulates the KATP channels in islet β cells. In this study, we aimed to verify the anti‐inflammatory effect of NaB on PD and further explored potential molecular mechanisms. Methods We established an in vitro PD model in BV2 cells using 1‐methyl‐4‐phenylpyridinium (MPP+). The effects of MPP+ and NaB on BV2 cell viability were detected by cell counting kit‐8 assays. The morphology of BV2 cells with or without MPP+ treatment was imaged via an optical microscope. The expression of Iba‐1 was examined by the immunofluorescence staining. The intracellular ATP content was estimated through the colorimetric method, and Griess assay was conducted to measure the nitric oxide production. The expression levels of pro‐inflammatory cytokines and KATP channel subunits were evaluated by reverse transcription–quantitative polymerase chain reaction and western blot analysis. Results NaB (5 mM) activated the KATP channels through elevating Kir6.1 and Kir6.1 expression in MPP+‐challenged BV2 cells. Both NaB and pinacidil (a KATP opener) suppressed the MPP+‐induced activation of BV2 cells and reduced the production of nitrite and pro‐inflammatory cytokines in MPP+‐challenged BV2 cells. Conclusion NaB treatment alleviates the MPP+‐induced inflammatory responses in microglia via activation of KATP channels. Sodium butyrate (NaB) retrains the activation of the proinflammatory phenotype of microglia by promoting KATP channel opening through enhancing the expression of Kir6.1 and Kir6.2.

The aim of the study is to compare the efficacy and safety of angioplasty alone with acute stenting for acute tandem occlusions (TO) due to internal carotid artery atherosclerotic. We identified 112 patients who underwent an endovascular treatment (EVT) for acute tandem internal carotid artery occlusions from the prospectively maintained registries 5 comprehensive stroke centers. The study cohort included 75 patients with underlying atherosclerotic lesion of the extracranial internal carotid artery, forty-five in the balloon angioplasty (BA) alone group and 30 in the acute stenting (AS) group. Using propensity score matching analysis, forty-four patients were matched. Clinical characteristics and outcome data were compared between two groups. The successful reperfusion immediately post procedure [72.7% (16/22) vs. 77.3% (17/22), P = 1.0] and 90-days good functional outcome [54.5% (12/22) vs. 59.1% (13/22), P = 0.761] were not significantly different between the BA group and AS group. There was also no significant difference in the rate of symptomatic intracranial hemorrhage [13.6% (3/22) vs. 9.1% (2/22), P = 1.00] and restenosis of ICA (>50%)[27.3% (6/22) vs. 22.7% (5/22), P = 0.728] between 2 groups. Patients in the BA group appear to have a numerically lower rate of asymptomatic intracranial hemorrhage [40.9% (9/22) vs. 50% (11/22), P = 0.545] and mortality [0 vs. 9.1% (2/22), P = 0.488] than in the AS group, although there were not statistically significant. Among TO patients with etiology of large vessel atherosclerosis, no statistical differences in outcome are identified between balloon angioplasty alone versus acute stenting. Future randomized controlled trials are warranted. •To retain the homogeneity of the enrolled patients, the presumed etiology of cervical carotid occlusion was related to the atherosclerotic disease were included from the analysis in our study.•A multicenter retrospective cohort study comparing the effectiveness and safety of balloon angioplasty alone with acute stenting in acute tandem occlusions (TO) due to atherosclerotic disease.•To control bias and minimize imbalance of baseline characteristics, we performed a 1:1 matched model based on the propensity score with the nearest neighbor-matching algorithm without replacement.•Among acute anterior tandem occlusion patients with etiology of large vessel atherosclerotic, no statistical differences in outcome are identified between balloon angioplasty alone versus acute stenting.•With this approach, futile acute stenting and higher procedural cost could be avoided.

L-2-Aminobutyric acid (L-2-ABA) is a non-proteinogenic amino acid and an important chiral intermediate widely used in pharmaceuticals and fine chemicals. However, its fermentative production is limited by intermediate toxicity and imbalanced metabolic flux. In this study, Escherichia coli was systematically engineered for efficient de novo synthesis of L-2-ABA using a multi-layer metabolic engineering strategy. A quorum-sensing–based dynamic control circuit was introduced to decouple cell growth from 2-oxobutyric acid formation, thereby alleviating precursor toxicity and improving flux coordination. Combined with optimization of the L-2-ABA conversion pathway, model-guided carbon flux redistribution, cofactor regeneration, and tuning of global transcriptional regulation, a high-performance production strain was obtained without the need for antibiotics or inducers. The final engineered strain ABA40 achieved 45.3 g/L L-2-ABA with a yield of 0.31 g/g glucose in a 72 h fed-batch fermentation. This study demonstrates the effectiveness of dynamic and integrated metabolic engineering strategies for the biosynthesis of non-natural amino acids. [Display omitted]

l -threonine is an integral nutrient for mammals, often used in animal feeds to enhance growth and reduce breeding costs. Developing l -threonine engineered strains that meet industrial production specifications has significant economic value. Here, we developed a biosensor that monitors l -threonine concentration to assist in high-throughput screening to capture high-yielding l -threonine mutants. Among them, the P cysK promoter and CysB protein were used to construct a primary l -threonine biosensor, and then the CysB T102A mutant was obtained through directed evolution resulting in a 5.6-fold increase in the fluorescence responsiveness of biosensor over the 0–4 g/L l -threonine concentration range. In addition, the metabolic network of mutant was further optimized through multi-omics analysis and in silico simulation. Ultimately, the THRM13 strain produced 163.2 g/L l -threonine, with a yield of 0.603 g/g glucose in a 5 L bioreactor. The biosensor constructed here could be employed for iterative upgrading of subsequent strains, and these engineering strategies described provide guidance for other chemical overproducers. Graphical Abstract

Accurate characterization of seafloor sediment properties is critical for marine engineering design, resource assessment, and environmental management. Sidescan sonar offers efficient wide-area mapping capabilities, yet establishing robust quantitative relationships between acoustic backscatter intensity and sediment texture remains challenging, particularly in heterogeneous coastal environments. This study investigates the correlation between sidescan sonar backscatter intensity and sediment grain size parameters in waters southwest of Hainan Island, China. High-resolution acoustic data (450 kHz) were acquired alongside surface sediment samples from 18 stations spanning diverse sediment types. Backscatter intensity, represented by grayscale values, was systematically compared with grain size distributions and individual size fractions. Results reveal that mean grain size shows no meaningful correlation with backscatter intensity; however, fine sand fraction content (0.075–0.25 mm) exhibits a strong negative linear relationship (R2 = 0.87 under optimal conditions). Distribution-level analysis demonstrates that backscatter variability mirrors sediment textural complexity, with coarse sediments producing broad, elevated intensity distributions and fine sediments yielding narrow, suppressed distributions. Inter-survey variability highlights the sensitivity of absolute intensity values to environmental conditions during acquisition. Spatial distribution analysis reveals that sediment grain size follows a systematic NE-SW gradient controlled by hydrodynamic energy, with notable local anomalies controlled by reef structures (producing coarse bioclastic sediment) and topographic sheltering (maintaining fine-grained deposits in shallow areas). These findings provide a quantitative basis for fraction-specific acoustic classification approaches while emphasizing the importance of multi-scale analysis incorporating both regional hydrodynamic trends and local morphological controls. The established relationship between fine sand abundance and acoustic response enables semi-quantitative sediment prediction from remotely sensed data, supporting improved seafloor mapping protocols for offshore infrastructure siting, aggregate resource evaluation, and coastal zone management in morphologically complex environments.

IntroductionEssential tremor (ET), a tremor disorder, is one of the most common movement disorders. Only oral drugs (propranolol, primidone, topiramate, etc）are still the first-line treatment recommended by the Food and Drug Administration. Propranolol is thought to potentially reduce upper limb action tremor. However, it has a poor effect on axial tremor symptoms, such as essential head tremor and voice tremor. Studies have shown that tremor severity develops over time, possibly producing other clinical tremors and neurological soft signs (such as memory loss, gait abnormalities, balance disorders, etc), which further increases the difficulty of treating tremors. However, some recent studies provide emerging evidence for oral propranolol on subgroups of ET, which is based on the anatomical distribution of ET (lower extremities, head, sound, tongue, etc). This systematic review aims to synthesise these new data to improve the efficacy of propranolol in ET subgroups.Methods and analysisWe will search for randomised controlled trials from the PubMed, MEDLINE, EMBASE, Cochrane Library, UptoDate and PEDro databases from inception to June 2019. All data will be extracted independently by two reviewers and compared at the end of the review. The two reviewers will screen the study quality, and the Cochrane Collaboration’s tool in Review Manager (RevMan) V.5.3.3 will be used to evaluate risk of bias. Our primary outcome will be the functional disability component related to tremors, as measured by the Fahn-Tolosa-Marin Tremor Rating Scale subscales B and C. Secondary outcomes will include severity of tremors and quality of life. Narrative and meta-analytical syntheses are planned.Ethics and disseminationPublished aggregated data will be used in this review analysis and therefore no ethical approval is required. The results will be published in peer-reviewed journals, and proliferation activities will include diverse social stakeholders, non-academic groups and patients.PROSPERO registration numberCRD42018112580