Stability of electrostatically stabilized emulsions and its encapsulation of astaxanthin against environmental stresses: Effect of sodium caseinate-sugar beet pectin addition order.

Two addition orders, i.e., the layer-by-layer (L) and mixed biopolymer (M) orders, were used to generate sodium caseinate - sugar beet pectin electrostatically stabilized o/w emulsions with 0.5% oil and varying sodium caseinate: sugar beet pectin ratios (3:1-1:3) at pH 4.5. Emulsion stability against environmental stresses (i.e., pH, salt addition, thermal treatment, storage and in vitro simulated gastrointestinal digestion) and its astaxanthin encapsulation against degradation during storage and in vitro digestion were evaluated. Results indicated that a total biopolymer concentration of 0.5% was optimal, with the preferred sodium caseinate-sugar beet pectin ratios for L and M emulsions being 1:1 and 1:3, respectively. L emulsions generally exhibited smaller droplet diameters than M emulsions across all ratios, except at 1:3. Lowering the pH to 1.5 substantially reduced the net negative charge of all emulsions, with only L emulsions precipitating at pH 3. M emulsions showed greater tolerance to salt addition, remaining stable up to 500 mM sodium and calcium concentrations, whereas L emulsions destabilized at levels exceeding 50 mM and 30 mM, respectively. All emulsions were stable when heated at 37 °C or 90 °C for 30 min. Astaxanthin degradation rates increased with prolonged storage, reaching 61.66% and 54.08% by day 7 for L and M emulsions, respectively. Encapsulation efficiency of astaxanthin in freshly prepared M emulsions (86.85%) was significantly higher compared to L emulsions (72.82%). M emulsions had 30% and 25% higher encapsulation efficiency of astaxanthin than L emulsions after in vitro digestion for 120 min and 240 min respectively. This study offers suggestions for interface design and process optimization to improve the performance of protein-polysaccharide emulsion systems, such as in beverages and dairy products, as well as their delivery effect of bioactives.

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Reasonable soybean-maize intercropping mode can effectively promote soil phosphorus turnover and crop phosphorus absorption, and reduce phosphorus fertilizer input. To optimize phosphorus (P)-use efficiency in soybean/maize intercropping system, we intercropped two genotypes of soybean with maize to investigate the rhizosphere processes and mechanisms underlying soil biological P fractions and crop P uptake. The results showed that intercropping significantly depleted the rhizosphere soluble inorganic P (CaCl2-P) content in soybean genotype Yuechun 03-3, without impact on the P fractions in the rhizosphere of soybean Essex. Similarly, intercropping significantly increased biomass and P uptake of soybean genotype Yuechun 03-3 by 42.2% and 46.9%, respectively, compared to monoculture. However, it did not affect P uptake and biomass of soybean Essex and maize. Intercropping significantly increased both the total root length and the quantity of root exudates in Yuechun 03-3 by 19.7% and 138.1%, respectively. There was a significant positive correlation between P uptake and total root length in Yuechun 03-3, while a significant negative correlation between soluble inorganic P content and P uptake. In summary, intercropping of soybean and maize exhibited noticeable genotype differences in its impact on soil P fractions and crop P uptake. Intercropping has the potential to improve soybean P uptake and rhizosphere P turnover, mainly by increasing root length and root exudates of P-efficient genotype. The study would provide scientific evidence for optimizing the pairing of soybean and maize varieties in intercropping systems, thereby enhancing phosphorus utilization efficiency and reducing fertilizer inputs.

IL23R-specific CAR Tregs for the treatment of Crohn's disease.

BACKGROUND AND AIMS: Regulatory T cells (Tregs) are key regulators in maintaining tissue homeostasis. Disrupted immune homeostasis is associated with Crohn's disease (CD) pathogenesis. Thus, Treg therapy represents a promising long-acting treatment to restore immune balance in the diseased intestine. CAR (Chimeric Antigen Receptor) T-cell therapy has revolutionized cancer treatment. This innovative approach also provides the opportunity to improve therapy for CD. By targeting a disease-relevant protein, Interleukin-23 receptor (IL23R), we engineered Tregs expressing IL23R-CAR for treating active CD. METHODS: Intestinal IL23R expression from active CD was verified by immunohistochemical analysis. Phenotypic and functional characteristics of IL23R-CAR Tregs were assessed using in vitro assays and their migration capacity was monitored in a xenograft tumor model. Transcriptomic and proteomic analyses were performed to associate molecular profiles with IL23R-CAR Treg activation against colon biopsy-derived cells from active CD patients. RESULTS: Our study showed that IL23R-CAR displayed negligible tonic signalling and strong signal-to-noise ratio. IL23R-CAR Tregs maintained regulatory phenotype during in vitro expansion, even when chronically exposed to proinflammatory cytokines and target antigen. IL23R engagement on IL23R-CAR Tregs triggered CAR-specific activation and significantly enhanced their suppressive activity. Also, IL23R-CAR Tregs migrated to IL23R-expressing tissue in humanized mice. Finally, IL23R-CAR Tregs elicited a specific activation against colon biopsy-derived cells from active CD, suggesting an efficient CAR engagement in active CD. Molecular profiling of CD patient biopsies also revealed transcriptomic and proteomic patterns associated with IL23R-CAR activation. CONCLUSIONS: Overall, our results demonstrate that IL23R-CAR Tregs represent a promising therapy for active CD.

Development and validation of a hypoxia- and mitochondrial dysfunction- related prognostic model based on integrated single-cell and bulk RNA sequencing analyses in gastric cancer.

Introduction: Gastric cancer (GC) remains a major global health threat ranking as the fifth most prevalent cancer. Hypoxia, a characteristic feature of solid tumors, significantly contributes to the malignant progression of GC. Mitochondria are the major target of hypoxic injury that promotes mitochondrial dysfunction during the development of cancers including GC. However, the gene signature and prognostic model based on hypoxia- and mitochondrial dysfunction-related genes (HMDRGs) in the prediction of GC prognosis have not yet been established. Methods: The gene expression profile datasets of stomach cancer patients were retrieved from The Cancer Genome Atlas and the Gene Expression Omnibus databases. Prognostic genes were selected using Least Absolute Shrinkage and Selection Operator Cox (LASSO-Cox) regression analysis to construct a prognostic model. Immune infiltration was evaluated through ESTIMATE, CIBERSORT, and ssGSEA analyses. Tumor immune dysfunction and exclusion (TIDE) and immunophenoscore (IPS) were utilized to explore implications for immunotherapy. Furthermore, in vitro experiments were conducted to validate the functional roles of HMDRGs in GC cell malignancy. Results: In this study, five HMDRGs (ZFP36, SERPINE1, DUSP1, CAV1, and AKAP12) were identified for developing a prognostic model in GC. This model stratifies GC patients into high- and low-risk groups based on median risk scores. A nomogram predicting overall survival (OS) was constructed and showed consistent results with observed OS. Immune infiltration analysis indicated that individuals in the high-risk group tend to exhibit increased immune cell infiltration. Additionally, analysis of cancer immunotherapy responses revealed that high-risk group patients exhibit poorer responses to cancer immunotherapy compared to the low-risk group. Immunohistochemistry (IHC) staining indicated that the expression levels of HMDRGs were remarkably correlated with GC, of which, SERPINE1 displayed the most pronounced up-regulation, while ZFP36 exhibited the most notable down-regulation in GC patients. Furthermore, in vitro investigation validated that SERPINE1 and ZFP36 contribute to the malignant processes of GC cells correlated with mitochondrial dysfunction. Conclusions: This study presents a novel and efficient approach to evaluate GC prognosis and immunotherapy efficacy, and also provides insights into understanding the pathogenesis of GC.

A wearable, rapidly manufacturable, stability-enhancing microneedle patch for closed-loop diabetes management.

The development of a wearable, easy-to-fabricate, and stable intelligent minisystem is highly desired for the closed-loop management of diabetes. Conventional systems always suffer from large size, high cost, low stability, or complex fabrication. Here, we show for the first time a wearable, rapidly manufacturable, stability-enhancing microneedle patch for diabetes management. The patch consists of a graphene composite ink-printed sensor on hollow microneedles, a polyethylene glycol (PEG)-functionalized electroosmotic micropump integrated with the microneedles, and a printed circuit board for precise and intelligent control of the sensor and pump to detect interstitial glucose and deliver insulin through the hollow channels. Via synthesizing and printing the graphene composite ink, the sensor fabrication process is fast and the sensing electrodes are stable. The PEG functionalization enables the micropump a significantly higher stability in delivering insulin, extending its lifetime from days to weeks. The patch successfully demonstrated excellent blood glucose control in diabetic rats. This work may introduce a new paradigm for building new closed-loop systems and shows great promise for widespread use in patients with diabetes.

Arctiin Mitigates Neuronal Injury by Modulating the P2X7R/NLPR3 Inflammasome Signaling Pathway.

Depression, recognized globally as a primary cause of disability, has its pathogenesis closely related to neuroinflammation and neuronal damage. Arctiin (ARC), the major bioactive component of Fructus arctii, has various pharmacological activities, such as anti-inflammatory and neuroprotective effects. Building on previous findings that highlighted ARC's capability to mitigate depression by dampening microglial hyperactivation and thereby reducing neuroinflammatory responses and cortical neuronal damage in mice, the current study delves deeper into ARC's therapeutic potential by examining its impact on hippocampal neuronal damage in depression. Utilizing both chronic unpredictable mild stress (CUMS)-induced depression model in mice and corticosterone (CORT)-stimulated PC12 cell model of neuronal damage, the techniques including Nissl staining, immunohistochemistry, western blotting, ELISA, lactate dehydrogenase assays, colony formation assays, immunofluorescence staining and molecular docking were employed to unravel the mechanisms behind ARC's neuroprotective effects. The findings revealed that ARC not only mitigates hippocampal neuropathological damage and reduces serum CORT levels in CUMS-exposed mice but also enhances cell activity while reducing lactate dehydrogenase release in CORT-stimulated PC12 cells. ARC attenuated neuroinflammatory responses and neuronal apoptosis by inhibiting the overactivation of the P2X7 receptor (P2X7R)/NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome signaling pathway, similar to the effect of A438079 (P2X7R antagonist). Interestingly, pretreatment with A438079 blocked the neuroprotective effect of ARC. Computer modeling predicted that both ARC and A438079 have strong binding with P2X7R and they have the same binding site. These results suggested that ARC may exert a neuroprotective role by binding to P2X7R, thereby inhibiting the P2X7R/NLRP3 inflammasome signaling pathway.

Insight into the Role of Rb Doping for Highly Efficient Kesterite Cu2ZnSn(S,Se)4 Solar Cells.

Various copper-related defects in the absorption layer have been a key factor impeding the enhancement of the efficiency of Cu2ZnSn(S,Se)4 (CZTSSe) solar cells. Alkali metal doping is considered to be a good strategy to ameliorate this problem. In this article, Rb-doped CZTSSe (RCZTSSe) thin films were synthesized using the sol-gel technique. The results show that the Rb atom could successfully enter into the CZTSSe lattice and replace the Cu atom. According to SEM results, a moderate amount of Rb doping aided in enhancing the growth of grains in CZTSSe thin films. It was proven that the RCZTSSe thin film had the densest surface morphology and the fewest holes when the doping content of Rb was 2%. In addition, Rb doping successfully inhibited the formation of CuZn defects and correlative defect clusters and promoted the electrical properties of RCZTSSe thin films. Finally, a remarkable power conversion efficiency of 7.32% was attained by the champion RCZTSSe device with a Rb content of 2%. Compared with that of un-doped CZTSSe, the efficiency improved by over 30%. This study offers new insights into the influence of alkali metal doping on suppressing copper-related defects and also presents a viable approach for improving the efficiency of CZTSSe devices.

miR-93-5p impairs autophagy-lysosomal pathway via TET3 after subarachnoid hemorrhage.

Intact autophagy-lysosomal pathway (ALP) in neuronal survival is crucial. However, it remains unclear whether ALP is intact after subarachnoid hemorrhage (SAH). Ten-eleven translocation (TET) 3 primarily regulates genes related to autophagy in neurons in neurodegenerative diseases. This study aims to investigate the role of TET3 in the ALP following SAH. The results indicate that the ALP is impaired after SAH, with suppressed autophagic flux and an increase in autophagosomes. This is accompanied by a decrease in TET3 expression. Activation of TET3 by α-KG can improve ALP function and neural function to some extent. Silencing TET3 in neurons significantly inhibited the ALP function and increased apoptosis. Inhibition of miR-93-5p, which is elevated after SAH, promotes TET3 expression. This suggests that the downregulation of TET3 after SAH is, at least in part, due to elevated miR-93-5p. This study clarifies the key role of TET3 in the functional impairment of the ALP after SAH. The preliminary exploration revealed that miR-93-5p could lead to the downregulation of TET3, which could be a new target for neuroprotective therapy after SAH.

Paeoniflorin suppresses ferroptosis after traumatic brain injury by antagonizing P53 acetylation.

BACKGROUND: Traumatic brain injury (TBI) could induce multiple forms of cell death, ferroptosis, a novel form of cell death distinct from apoptosis and autophagy, plays an important role in disease progression in TBI. Therapies targeting ferroptosis are beneficial for recovery from TBI. Paeoniflorin (Pae) is a water-soluble monoterpene glycoside and the active ingredient of Paeonia lactiflora pall. It has been shown to exert anti-inflammatory and antioxidant effects. However The effects and mechanisms of paeoniflorin on secondary injury after TBI are unknown. PURPOSE: To investigate the mechanism by which Pae regulates ferroptosis after TBI. METHODS: The TBI mouse model and cortical primary neurons were utilized to study the protective effect of paeoniflorin on the brain tissue after TBI. The neuronal cell ferroptosis model was established by treating cortical primary neurons with erastin. Liproxstatin-1(Lip-1) was used as a positive control drug. Immunofluorescence staining, Nissl staining, biochemical analyses, pharmacological analyses, and western blot were used to evaluate the effects of paeoniflorin on TBI. RESULTS: Pae significantly ameliorated neuronal damage after TBI, inhibited mitochondrial damage, increased glutathione peroxidase 4 (GPX4) activity, decreased malondialdehyde (MDA) production, restored neurological function and inhibited cerebral edema. Pae promotes the degradation of P53 in the form of proteasome, promotes its ubiquitination, and reduces the stability of P53 by inhibiting its acetylation, thus alleviating the P53-mediated inhibition of cystine/glutamate antiporter solute carrier family 7 member 11 (SLC7A11) by P53. CONCLUSION: Pae inhibits ferroptosis by promoting P53 ubiquitination out of the nucleus, inhibiting P53 acetylation, and modulating the SLC7A11-GPX4 pathway.

TS-AI: A deep learning pipeline for multimodal subject-specific parcellation with task contrasts synthesis.

Accurate mapping of brain functional subregions at an individual level is crucial. Task-based functional MRI (tfMRI) captures subject-specific activation patterns during various functions and behaviors, facilitating the individual localization of functionally distinct subregions. However, acquiring high-quality tfMRI is time-consuming and resource-intensive in both scientific and clinical settings. The present study proposes a two-stage network model, TS-AI, to individualize an atlas on cortical surfaces through the prediction of tfMRI data. TS-AI first synthesizes a battery of task contrast maps for each individual by leveraging tract-wise anatomical connectivity and resting-state networks. These synthesized maps, along with feature maps of tract-wise anatomical connectivity and resting-state networks, are then fed into an end-to-end deep neural network to individualize an atlas. TS-AI enables the synthesized task contrast maps to be used in individual parcellation without the acquisition of actual task fMRI scans. In addition, a novel feature consistency loss is designed to assign vertices with similar features to the same parcel, which increases individual specificity and mitigates overfitting risks caused by the absence of individual parcellation ground truth. The individualized parcellations were validated by assessing test-retest reliability, homogeneity, and cognitive behavior prediction using diverse reference atlases and datasets, demonstrating the superior performance and generalizability of TS-AI. Sensitivity analysis yielded insights into region-specific features influencing individual variation in functional regionalization. Additionally, TS-AI identified accelerated shrinkage in the medial temporal and cingulate parcels during the progression of Alzheimer's disease, suggesting its potential in clinical research and applications.

Tumor-intrinsic P2RY6 drives immunosuppression by enhancing PGE2 production.

Despite the success of anti-programmed cell death-1 (anti-PD-1) immunotherapy, many cancer patients remain unresponsive, and reliable predictive biomarkers are lacking. Here, we show that aberrant expression of the pyrimidinergic receptor P2RY6 is frequent in human cancers and causes immune evasion. In mouse syngeneic and human xenograft tumor models, ectopic expression of P2RY6 shapes an immunosuppressive tumor microenvironment (TME) to enhance tumor growth and resistance to immunotherapy, whereas deletion of P2RY6 from tumors with high P2RY6 expression inflames the TME to inhibit tumor growth. As a G protein-coupled receptor, P2RY6 activates Gq/phospholipase C-ß signaling and stimulates the synthesis of prostaglandin E2, which is a key mediator of immunosuppression in the TME. In contrast to the essential role of P2RY6 in tumors, global deletion of P2ry6 from mice does not compromise viability. Our study thus nominates P2RY6 as a precision immunotherapy target for patients with high tumor-intrinsic P2RY6 expression.

Nanoarchitectonics of Vesicle Microreactors for Oscillating ATP Synthesis and Hydrolysis.

We construct a compartmentalized nanoarchitecture to regulate bioenergy level. Glucose dehydrogenase, urease and nicotinamide adenine dinucleotide are encapsulated inside through liquid-liquid phase separation. ATPase and glucose transporter embedded in hybrid liposomes are attached at the surface. Glucose is transported and converted to gluconic acid catalyzed by glucose dehydrogenase, resulting in an outward proton gradient to drive ATPase for ATP synthesis. In parallel, urease catalyzes hydrolysis of urea to generate ammonia, which leads to an inward proton gradient to drive ATPase for ATP hydrolysis. These processes lead to a change of the direction of proton gradient, thus achieving artificial ATP oscillation. Importantly, the frequency and the amplitude of the oscillation can be programmed. The work explores nanoarchitectonics integrating multiple components to realize artificial and precise oscillation of bioenergy level.

A novel bispecific antibody targeting two overlapping epitopes in RBD improves neutralizing potency and breadth against SARS-CoV-2.

SARS-CoV-2 has been evolving into a large number of variants, including the highly pathogenic Delta variant, and the currently prevalent Omicron subvariants with extensive evasion capability, which raises an urgent need to develop new broad-spectrum neutralizing antibodies. Herein, we engineer two IgG-(scFv)2 form bispecific antibodies with overlapping epitopes (bsAb1) or non-overlapping epitopes (bsAb2). Both bsAbs are significantly superior to the parental monoclonal antibodies in terms of their antigen-binding and virus-neutralizing activities against all tested circulating SARS-CoV-2 variants including currently dominant JN.1. The bsAb1 can efficiently neutralize all variants insensitive to parental monoclonal antibodies or the cocktail with IC50 lower than 20 ng/mL, even slightly better than bsAb2. Furthermore, the cryo-EM structures of bsAb1 in complex with the Omicron spike protein revealed that bsAb1 with overlapping epitopes effectively locked the S protein, which accounts for its conserved neutralization against Omicron variants. The bispecific antibody strategy engineered from overlapping epitopes provides a novel solution for dealing with viral immune evasion.

Hypoxia Postconditioning Attenuates Hypoxia-Induced Inflammation and Endothelial Barrier Dysfunction.

INTRODUCTION: In recent years, a number of studies have demonstrated that hypoxia reoxygenation (HR) induced by ischemia postconditioning (IPC) reduces endothelial barrier dysfunction and inflammation in various models. When HR occurs, the P38 mitogen-activated protein kinase (P38 MAPK) breaks down the endothelial barrier. But no study has clearly clarified the effect of hypoxia postconditioning (HPC) on P38 MAPK in human dermal microvascular endothelial cells. Therefore, we investigated the function of HPC on P38 MAPK during HR in vitro. METHODS: Human dermal microvascular endothelial cells were cultured in a hypoxic incubator for 8 h. Then cells were reperfused for 12 h (reoxygenation) or postconditioned by 5 min of reoxygenation and 5 min of re-hypoxia 3 times followed by 11.5 h reoxygenation. SB203580 was used as an inhibitor of P38 MAPK. Cell counting kit-8 assay kits were employed to detect cell activity. The corresponding levels of IL-6, IL-8 and IL-1ß were examined via Enzyme-Linked ImmunoSorbent Assay. The endothelial barrier was evaluated using fluorescein isothiocyanate-dextran leakage assay. Western blot was used to detect claudin-5, phosphorylation of P38 MAPK (P-P38 MAPK) and P38 MAPK expression. Claudin-5 localization was studied by immunofluorescence. RESULTS: HR induced endothelial barrier hyperpermeability, elevated inflammation levels, and increased the P-P38 MAPK. But HPC reduced cell injury and maintained the integrity of the endothelial barrier while inhibiting P-P38 MAPK and increasing expression of claudin-5. HPC redistributed claudin-5 in a continuous and linear pattern on the cell membrane. CONCLUSIONS: HPC protects against HR induced downregulation and redistribution of claudin-5 by inhibiting P-P38 MAPK.

Recent Innovations and Technical Advances in High-Throughput Parallel Single-Cell Whole-Genome Sequencing Methods.

Single-cell whole-genome sequencing (scWGS) detects cell heterogeneity at the aspect of genomic variations, which are inheritable and play an important role in life processes such as aging and cancer progression. The recent explosive development of high-throughput single-cell sequencing methods has enabled high-performance heterogeneity detection through a vast number of novel strategies. Despite the limitation on total cost, technical advances in high-throughput single-cell whole-genome sequencing methods are made for higher genome coverage, parallel throughput, and level of integration. This review highlights the technical advancements in high-throughput scWGS in the aspects of strategies design, data efficiency, parallel handling platforms, and their applications on human genome. The experimental innovations, remaining challenges, and perspectives are summarized and discussed.

UBE2C as an Immune-Related Biomarker for Breast Cancer: A Study Based on Multiple Databases.

Objective To screen the target gene UBE2C and explore its prognostic value and immune correlation in breast cancer (BRCA) using multiple databases. Methods The microarray expression datasets of BRCA were downloaded from the Gene Expresssion Omnibus database (GEO) and analyzed to obtain differentially expressed genes (DEGs). Hub genes were obtained by constructing and visualizing the protein-protein interaction network of DEGs. Then the key gene UBE2C was determined using R language, STRING, and Cytoscape, and the differential expression of UBE2C was verified using the external datasets, The Cancer Genome Atlas (TCGA) , and quantitative real-time PCR (qRT-PCR). The prognostic value and immunological correlation of UBE2C in BRCA were explored using R language, TIMER, and Gene Set Enrichment Analysis (GSEA).Results The expression of UBE2C was differentially upregulated in BRCA, as verified by TCGA and qRT-PCR. Prognostic analysis revealed that UBE2C served as an independent prognostic factor. High expression of UBE2C was associated with decreased immune infiltration levels of B cells, CD4+ T cells, CD8+ T cells, macrophages, and myeloid dendritic cells in BRCA tissue. The expression of UBE2C in BRCA showed a significant correlation with PDCD1, CD274, and CTLA4 expressions. There was a positive correlation between the expression of UBE2C and the tumor mutational burden and microsatellite instability. GSEA demonstrated that UBE2C expression significantly enriched 786 immune-related gene sets.Conclusions UBE2C expression in BRCA tissues can predict the survivals and prognosis of BRCA patients. Also, it is closely related to the BRCA immune microenvironment and can predict the effecacy of immunotherapy in BRCA patients. Therefore, UBE2C may be an potential immune-related prognostic biomarker for BRCA.

Characteristics of tunneling nanotube-like structures formed by human dermal microvascular pericytes in vitro.

Tunneling nanotubes (TNTs) represent an innovative way for cells to communicate with one another, as they act as long conduits between cells. However, their roles in human dermal microvascular pericytes (HDMPCs) interaction remain elusive in vitro. In this work, we identified and characterized the TNT-like structures that connected two or more pericytes in two-dimensional cultures and formed a functional network in the human dermis. Immunofluorescence assay indicated that the F-actin was an essential element to form inter-pericyte TNT-like structures, as it decreased in actin polymer inhibitor-cytochalasin B treated groups, and microtubules were present in almost half of the TNT-like structures. Most importantly, we only found the presence of mitochondrial in TNT-like structures containing α-tubulin, and the application of microtubule assembly inhibitor-Nocodazole significantly reduced the percentage of TNT-like structures that contain α-tubulin, resulting in a sudden decrease in the positive rate of cytochrome c oxidase subunit 4 isoform 1 (COX IV, a marker of mitochondria) in TNT-like structures. In summary, we described a novel intercellular communication-TNT-like structures-between HDMPCs in vitro, and this work allows us to properly understand the cellular mechanisms of spreading materials between HDMPCs, shedding light on the role of HDMPCs.

Large-scale lexical and genetic alignment supports a hybrid model of Han Chinese demic and cultural diffusions.

The Han Chinese history is shaped by substantial demographic activities and sociocultural transmissions. However, it remains challenging to assess the contributions of demic and cultural diffusion to Han culture and language, primarily due to the lack of rigorous examination of genetic-linguistic congruence. Here we digitized a large-scale linguistic inventory comprising 1,018 lexical traits across 926 dialect varieties. Using phylogenetic analysis and admixture inference, we revealed a north-south gradient of lexical differences that probably resulted from historical migrations. Furthermore, we quantified extensive horizontal language transfers and pinpointed central China as a dialectal melting pot. Integrating genetic data from 30,408 Han Chinese individuals, we compared the lexical and genetic landscapes across 26 provinces. Our results support a hybrid model where demic diffusion predominantly impacts central China, while cultural diffusion and language assimilation occur in southwestern and coastal regions, respectively. This interdisciplinary study sheds light on the complex social-genetic history of the Han Chinese.

Application of LAMP coupled with NALF for precise detection of mycoplasma pneumoniae.

Mycoplasma pneumoniae (MP),as the most commonly infected respiratory pathogen in community-acquired pneumonia in preschool children,has becoming a prominent factor affecting children's respiratory health.Currently, there is a lack of easy, rapid, and accurate laboratory testing program for MP infection, which causes comparatively difficulty for clinical diagnostic.Here,we utilize loop-mediated isothermal amplification (LAMP) to amplify and characterize the P1 gene of MP, combined with nucleic acid lateral flow (NALF) for fast and visuallized detection of MP.Furthermore, we evaluated and analyzed the sensitivity, specificity and methodological consistency of the method.The results showed that the limit of detection(LoD) of MP-LAMP-NALF assay was down to 100 copys per reaction and there was no cross-reactivity with other pathogens infected the respiratory system. The concordance rate between MP-LAMP-NALF assay with quantitative real-time PCR was 94.3 %,which exhibiting excellent testing performance.We make superior the turnaround time of the MP-LAMP-NALF assay, which takes only about 50 min. In addition, there is no need for precision instruments and no restriction on the laboratory site.Collectively, LAMP-NALF assay targeting the P1 gene for Mycoplasma pneumoniae detection was a easy, precise and visual test which could be widely applied in outpatient and emergency departments or primary hospitals.When further optimized, it could be used as "point-of-care testing" of pathogens or multiple testing for pathogens.

Clinical features of COVID-19-related encephalitis: comparison with the features of herpes virus encephalitis and autoimmune encephalitis.

INTRODUCTION: Identifying coronavirus disease 2019 (COVID-19)-related encephalitis without clear etiological evidence is clinically challenging. The distinctions between this condition and other prevalent encephalitis types remain unknown. Therefore, we aimed to explore the similarities and differences in the clinical characteristics of COVID-19-related encephalitis and other encephalitis types. METHODS: Adult patients with encephalitis admitted to the neurology department at Xuanwu Hospital were enrolled and categorized into the following six groups based on the results of metagenomic next-generation sequencing and autoimmune antibody detection in cerebrospinal fluid (CSF): COVID-19-related encephalitis (n = 36), herpes simplex virus type 1 encephalitis (HSV-1 encephalitis; n = 28), human herpesvirus 3 encephalitis (HHV-3 encephalitis; n = 10), NMDAR-antibody encephalitis (n = 18), LGI1-antibody encephalitis (n = 12), and GABAB-antibody encephalitis (n = 8). RESULTS: The predominant characteristics of COVID-19-related encephalitis include a low incidence of seizures (38.9%), cognitive defects (30.6%), and meningeal irritation signs (8.3%). Compared with HSV-1 and HHV-3 encephalitis, COVID-19-related encephalitis exhibited lower white blood cell count (2.5 count/mm3), protein (32.2 mg/dL), and immunoglobulin M, G, and A levels (0.09, 3.2, and 0.46 mg/dL, respectively) in the CSF tests. Abnormal imaging findings were present in only 36.1% of COVID-19-related encephalitis cases, mostly showing diffuse inflammation scattered in various parts, which differed from HSV-1 encephalitis. Additionally, COVID-19-related encephalitis exhibited significant differences in clinical symptoms and CSF white blood cell counts compared with NMDAR-antibody encephalitis; however, it showed limited differences compared with LGI1-antibody and GABAB-antibody encephalitis. DISCUSSION: COVID-19-related encephalitis and herpes virus or autoimmune encephalitis differ clinically. Symptoms and auxiliary examinations can be used as distinguishing tools.