Non-centrosymmetric topological phase probed by non-linear Hall effect.

Non-centrosymmetric topological material has attracted intense attention due to its superior characteristics as compared with the centrosymmetric one, although probing the local quantum geometry in non-centrosymmetric topological material remains challenging. The non-linear Hall (NLH) effect provides an ideal tool to investigate the local quantum geometry. Here, we report a non-centrosymmetric topological phase in ZrTe5, probed by using the NLH effect. The angle-resolved and temperature-dependent NLH measurement reveals the inversion and ab-plane mirror symmetries breaking at <30 K, consistently with our theoretical calculation. Our findings identify a new non-centrosymmetric phase of ZrTe5 and provide a platform to probe and control local quantum geometry via crystal symmetries.

MicroRNA-34 and gastrointestinal cancers: a player with big functions.

It is commonly assumed that gastrointestinal cancer is the most common form of cancer across the globe and is the leading contributor to cancer-related death. The intricate mechanisms underlying the growth of GI cancers have been identified. It is worth mentioning that both non-coding RNAs (ncRNAs) and certain types of RNA, such as circular RNAs (circRNAs), long non-coding RNAs (lncRNAs), and microRNAs (miRNAs), can have considerable impact on the development of gastrointestinal (GI) cancers. As a tumour suppressor, in the group of short non-coding regulatory RNAs is miR-34a. miR-34a silences multiple proto-oncogenes at the post-transcriptional stage by targeting them, which inhibits all physiologically relevant cell proliferation pathways. However, it has been discovered that deregulation of miR-34a plays important roles in the growth of tumors and the development of cancer, including invasion, metastasis, and the tumor-associated epithelial-mesenchymal transition (EMT). Further understanding of miR-34a's molecular pathways in cancer is also necessary for the development of precise diagnoses and effective treatments. We outlined the most recent research on miR-34a functions in GI cancers in this review. Additionally, we emphasize the significance of exosomal miR-34 in gastrointestinal cancers.

Diagnostic implications of ubiquitination-related gene signatures in Alzheimer's disease.

The purpose of this study was to explore the diagnostic implications of ubiquitination-related gene signatures in Alzheimer's disease. In this study, we first collected 161 samples from the GEO database (including 87 in the AD group and 74 in the normal group). Subsequently, through differential expression analysis and the iUUCD 2.0 database, we obtained 3450 Differentially Expressed Genes (DEGs) and 806 Ubiquitin-related genes (UbRGs). After taking the intersection, we obtained 128 UbR-DEGs. Secondly, by conducting GO and KEGG enrichment analysis on these 128 UbR-DEGs, we identified the main molecular functions and biological pathways related to AD. Furthermore, through the utilization of GSEA analysis, we have gained insight into the enrichment of functions and pathways within both the AD and normal groups. Further, using lasso regression analysis and cross-validation techniques, we identified 22 characteristic genes associated with AD. Subsequently, we constructed a logistic regression model and optimized it, resulting in the identification of 6 RUbR-DEGs: KLHL21, WDR82, DTX3L, UBTD2, CISH, and ATXN3L. In addition, the ROC result showed that the diagnostic model we built has excellent accuracy and reliability in identifying AD patients. Finally, we constructed a lncRNA-miRNA-mRNA (competing endogenous RNA, ceRNA) regulatory network for AD based on six RUbR-DEGs, further elucidating the interaction between UbRGs and lncRNA, miRNA. In conclusion, our findings will contribute to further understanding of the molecular pathogenesis of AD and provide a new perspective for AD risk prediction, early diagnosis and targeted therapy in the population.

Intraspecific and interspecific variations in the synonymous codon usage in mitochondrial genomes of 8 pleurotus strains.

In this study, we investigated the codon bias of twelve mitochondrial core protein coding genes (PCGs) in eight Pleurotus strains, two of which are from the same species. The results revealed that the codons of all Pleurotus strains had a preference for ending in A/T. Furthermore, the correlation between codon base compositions and codon adaptation index (CAI), codon bias index (CBI) and frequency of optimal codons (FOP) indices was also detected, implying the influence of base composition on codon bias. The two P. ostreatus species were found to have differences in various base bias indicators. The average effective number of codons (ENC) of mitochondrial core PCGs of Pleurotus was found to be less than 35, indicating strong codon preference of mitochondrial core PCGs of Pleurotus. The neutrality plot analysis and PR2-Bias plot analysis further suggested that natural selection plays an important role in Pleurotus codon bias. Additionally, six to ten optimal codons (ΔRSCU > 0.08 and RSCU > 1) were identified in eight Pleurotus strains, with UGU and ACU being the most widely used optimal codons in Pleurotus. Finally, based on the combined mitochondrial sequence and RSCU value, the genetic relationship between different Pleurotus strains was deduced, showing large variations between them. This research has improved our understanding of synonymous codon usage characteristics and evolution of this important fungal group.

Sources and fate of omega-3 polyunsaturated fatty acids in a highly eutrophic lake.

Omega-3 polyunsaturated fatty acids (ω3-PUFA) are central to the growth and reproduction of aquatic consumers. Dissolved nutrients in aquatic ecosystems strongly affect algal taxonomic composition and thus the production and transfer of specific ω3-PUFA to consumers at higher trophic levels. However, most studies were conducted in nutrient-poor, oligotrophic lakes, leading to an insufficient understanding of how water nutrients affect algal ω3-PUFA and their trophic transfer in consumers in highly eutrophic lakes. We conducted a field investigation in a highly eutrophic lake and collected basal food sources (phytoplankton, periphyton and macrophytes) and aquatic consumers (invertebrates, zooplankton and fish), and measured their fatty acid (FA) composition. Our results showed that periphyton and phytoplankton were both important sources of ω3-PUFA supporting the highly eutrophic lake food web. High water nutrient levels led to low ω3-PUFA levels in phytoplankton and periphyton, resulting in decreased nutritional quality. Consequently, ω3-PUFA of invertebrates and zooplankton reflected variations in ω3-PUFA of phytoplankton and periphyton, respectively. The ω3-PUFA levels of fish decreased as phytoplankton and periphyton ω3-PUFA decreased. Among fish, the Redfin Culter (Cultrichthys erythropterus) and Bar Cheek Goby (Rhinogobius giurinus) exhibited significantly higher levels of EPA and DHA compared to the Pond Loach (Misgurnus anguillicaudatus), which may have been caused by their different feeding modes. Decreases in the ω3-PUFA levels of basal food sources may be one of the causes leading to the reduction of trophic links in aquatic food webs. Our study elucidated the sources and fate of ω3-PUFA in highly eutrophic lakes, complemented previous studies in oligo- and mesotrophic lakes, and emphasized the role of high-quality food sources. Our results offer new perspectives for the conservation and management of highly eutrophic lake ecosystems.

PAX6 promotes neuroendocrine phenotypes of prostate cancer via enhancing MET/STAT5A-mediated chromatin accessibility.

BACKGROUND: Neuroendocrine prostate cancer (NEPC) is a lethal subset of prostate cancer which is characterized by neuroendocrine differentiation and loss of androgen receptor (AR) signaling. Growing evidence reveals that cell lineage plasticity is crucial in the failure of NEPC therapies. Although studies suggest the involvement of the neural transcription factor PAX6 in drug resistance, its specific role in NEPC remains unclear. METHODS: The expression of PAX6 in NEPC was identified via bioinformatics and immunohistochemistry. CCK8 assay, colony formation assay, tumorsphere formation assay and apoptosis assay were used to illustrate the key role of PAX6 in the progression of in vitro. ChIP and Dual-luciferase reporter assays were conducted to confirm the binding sequences of AR in the promoter region of PAX6, as well as the binding sequences of PAX6 in the promoter regions of STAT5A and MET. For in vivo validation, the xenograft model representing NEPC subtype underwent pathological analysis to verify the significant role of PAX6 in disease progression. Complementary diagnoses were established through public clinical datasets and transcriptome sequencing of specific cell lines. ATAC-seq was used to detect the chromatin accessibility of specific cell lines. RESULTS: PAX6 expression was significantly elevated in NEPC and negatively regulated by AR signaling. Activation of PAX6 in non-NEPC cells led to NE trans-differentiation, while knock-down of PAX6 in NEPC cells inhibited the development and progression of NEPC. Importantly, loss of AR resulted in an enhanced expression of PAX6, which reprogramed the lineage plasticity of prostate cancer cells to develop NE phenotypes through the MET/STAT5A signaling pathway. Through ATAC-seq, we found that a high expression level of PAX6 elicited enhanced chromatin accessibility, mainly through attenuation of H4K20me3, which typically causes chromatin silence in cancer cells. CONCLUSION: This study reveals a novel neural transcription factor PAX6 could drive NEPC progression and suggest that it might serve as a potential therapeutic target for the management of NEPC.

Efficacy and safety of continuous nursing in improving functional recovery after total hip or knee arthroplasty in older adults: A systematic review.

Objective: This systematic review was conducted to evaluate the efficacy and safety of continuous nursing care for the recovery of joint function in older adults with total hip or knee arthroplasty. Methods: Randomized controlled trials and cohort studies of continuous nursing in older patients after joint replacement were searched from the database of Cochrane Library, Web of Science, PubMed, and Embase from their establishment to October 25, 2023. After literature screening, two researchers completed data extraction, and the risk of bias was assessed using the Cochrane risk-of-bias tool. The risk analysis included in cohort studies was based on the Newcastle-Ottawa Scale (NOS). Results: The study included a total of 15 articles, comprising 34,186 knee and hip replacement patients. In this review, the effects of continuous nursing on the recovery of joint function of knee replacement and hip replacement in older adults were classified and discussed. Continuous nursing interventions targeted for total hip replacement could greatly increase the range of joint mobility, enhance muscle strength during hip movements like flexion, extension, and abduction, maintain joint stability, relieve pain, improve daily activities, and lower the risk of complications. For older patients with knee arthroplasty, continuous nursing programs could markedly improve knee motion range, joint flexion, joint stability, daily activities, and pain management. Despite the implementation of interventions, the incidence of complications caused by total knee replacement did not decrease. Out of all the studies reviewed, only one used a theoretical framework for interventions provided to patients during the postoperative period of hip arthroplasty. The overall quality of the included studies was very high. Conclusion: Continuous nursing can effectively improve the joint function of older patients after joint replacement. However, its effectiveness in terms of clinical outcomes, patient satisfaction, and medical cost of associated continuous nursing needs to be further clarified. In addition, continuous nursing has no significant advantage in the safety of postoperative complications and readmission rates in older adults after knee joint replacement. To enhance the efficacy and safety of continuous nursing effectively, it is crucial to refine the continuous nursing program in the future, thereby elevating the quality of nursing services.

Effects of garlic-derived fructan and oligofructose mixtures on intestinal health and constipation relief in mice.

BACKGROUND: Garlic polysaccharides (GPs) constitute over 75% of the dry weight of garlic. They are characterized by fructan with a 2,1-ß-d-Fruf backbone and 2,6-ß-d-Fruf branches. Studies have suggested a role for GPs in regulating gut microbiota but whether they possess a comprehensive function in maintaining intestinal well-being and can serve as effective prebiotics remains unknown. To explore this, varied doses of GPs (1.25-5.0 g kg-1 body weight) and inulin (as a positive control) were administered to Kunming mice via gavage, and their effects on the intestinal epithelial, chemical, and biological barriers were assessed. A constipation model was also established using loperamide to investigate the potential effects of GPs on the relief of constipation. RESULTS: Administration of GPs significantly upregulated expression of tight-junction proteins and mucins in Kunming mouse small-intestine tissue. Garlic polysaccharides elevated cecal butyric acid content, reduced the abundance of Desulfobacterota, and decreased the ratio of Firmicutes to Bacteroidetes (the F/B ratio). Garlic polysaccharides also promoted the growth of Bacteroides acidifaciens and Clostridium saccharogumia. Tax4Fun functional predictions suggested the potential of GPs to prevent human diseases, reducing the risk of insulin resistance, infectious diseases, and drug resistance. Garlic polysaccharides also exhibited a beneficial effect in alleviating loperamide-induced constipation symptoms by enhancing small intestinal transit, softening stool consistency, accelerating bowel movements, and promoting the release of excitatory neurotransmitters. CONCLUSIONS: These findings highlight the important role of GPs in maintaining gut fitness by enhancing intestinal barrier function and peristalsis. Garlic polysaccharides are promising prebiotics, potentially contributing to overall intestinal well-being and health. © 2024 Society of Chemical Industry.

The biological behavior and clinical outcome of pituitary adenoma are affected by the microenvironment.

BACKGROUND: Pituitary adenoma is one of the most common brain tumors. Most pituitary adenomas are benign and can be cured by surgery and/or medication. However, some pituitary adenomas show aggressive growth with a fast growth rate and are resistant to conventional treatments such as surgery, drug therapy, and radiation therapy. These tumors, referred to as refractory pituitary adenomas, often relapse or regrow in the early postoperative period. The tumor microenvironment (TME) has recently been identified as an important factor affecting the biological manifestations of tumors and acts as the main battlefield between the tumor and the host immune system. MAIN BODY: In this review, we focus on describing TME in pituitary adenomas and refractory pituitary adenomas. Research on the immune microenvironment of pituitary adenomas is currently focused on immune cells such as macrophages and lymphocytes, and extensive research and experimental verifications are still required regarding other components of the TME. In particular, studies are needed to determine the role of the TME in the specific biological behaviors of refractory pituitary adenomas, such as high invasion, fast recurrence rate, and high tolerance to traditional treatments and to identify the mechanisms involved. CONCLUSION: Overall, we summarize the similarities and differences between the TME of pituitary adenomas and refractory pituitary adenomas as well as the changes in the biological behavior of pituitary adenomas that may be caused by the microenvironment. These changes greatly affect the outcome of patients.

Network Pharmacology Combined with Animal Models to Investigate the Mechanism of ChangPu YuJin Tang in the Treatment of Tourette Syndrome.

BACKGROUND: ChangPu YuJin Tang (CPYJT) is a Chinese herbal formula that has been shown to be an effective therapeutic strategy for pediatric patients with Tourette Syndrome (TS). Using an integrated strategy of network pharmacology and animal model, the aim of this study was to investigate the mechanism of CPYJT in the treatment of TS. METHODS: Compound libraries of CPYJT were established using databases, such as the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The TCMSP database and Swiss Target Prediction database were used to predict the targets. The above results were constructed into a CPYJT-Drug-Component-Target network. Moreover, TS targets were predicted using GeneCards and other databases. The targets corresponding to the potential ingredients in CPYJT and the targets corresponding to TS were taken as the intersections to construct the CPYJT-TS network. The target network was analysed by PPI using the string database. GO and KEGG enrichment analyses were performed on the target network. The whole process was performed using Cytoscape 3.7.2 to make visual network diagrams of the results. CPYJT was characterised by Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry (UHPLC-MS). Transmission Electron Microscopy (TEM) was used to observe the structural changes of CPYJT on the neuronal cells of the IDPN model rats. RT-PCR and Western Blot were used to analyse the changes in the mRNA and protein expression levels of BDNF, TrkB, PI3K, and AKT in the cortex, striatum, and thalamus brain regions after CPYJT administration in IDPN model rats. RESULTS: Network pharmacology and UHPLC-MS studies revealed that CPYJT acted on the TS through multiple neurotransmitters and the BDNF/TrkB and PI3K/AKT signalling pathways. CPYJT ameliorated neurocellular structural damage in the cortex, striatum, and thalamus of TS model rats. Additionally, CPYJT up-regulated the levels of BDNF, TrkB, PI3k, and AKT in the cortex, striatum, and thalamus of TS model rats. CONCLUSION: It was found that CPYJT protected neuronal cells from structural damage in multiple brain regions and affected the expression levels of BDNF, TrkB, PI3K, and Akt in the cortex, striatum, and thalamus during TS treatment.

Atypical functional connectivity between the amygdala and visual, salience regions in infants with genetic liability for autism.

The amygdala undergoes a period of overgrowth in the first year of life, resulting in enlarged volume by 12 months in infants later diagnosed with ASD. The overgrowth of the amygdala may have functional consequences during infancy. We investigated whether amygdala connectivity differs in 12-month-olds at high likelihood (HL) for ASD (defined by having an older sibling with autism), compared to those at low likelihood (LL). We examined seed-based connectivity of left and right amygdalae, hypothesizing that the HL and LL groups would differ in amygdala connectivity, especially with the visual cortex, based on our prior reports demonstrating that components of visual circuitry develop atypically and are linked to genetic liability for autism. We found that HL infants exhibited weaker connectivity between the right amygdala and the left visual cortex, as well as between the left amygdala and the right anterior cingulate, with evidence that these patterns occur in distinct subgroups of the HL sample. Amygdala connectivity strength with the visual cortex was related to motor and communication abilities among HL infants. Findings indicate that aberrant functional connectivity between the amygdala and visual regions is apparent in infants with genetic liability for ASD and may have implications for early differences in adaptive behaviors.

Wheat peptide alleviates DSS-induced colitis by activating the Keap1-Nrf2 signaling pathway and maintaining the integrity of the gut barrier.

Inflammatory bowel disease (IBD) is difficult to cure, and formulating a dietary plan is an effective means to prevent and treat this disease. Wheat peptide contains a variety of bioactive peptides with anti-inflammatory and antioxidant functions. The results of this study showed that preventive supplementation with wheat peptide (WP) can significantly alleviate the symptoms of dextran sulfate sodium (DSS)-induced colitis in mice. WP can increase body weight, alleviate colon shortening, and reduce disease activity index (DAI) scores. In addition, WP improved intestinal microbial disorders in mice with colitis. Based on LC-MS, a total of 313 peptides were identified in WP, 4 of which were predicted to be bioactive peptides. The regulatory effects of WP and four bioactive peptides on the Keap1-Nrf2 signaling pathway were verified in Caco-2 cells. In conclusion, this study demonstrated that WP alleviates DSS-induced colitis by helping maintain gut barrier integrity and targeting the Keap1-Nrf2 axis; these results provided a rationale for adding WP to dietary strategies to prevent IBD.

Echinacea purpurea Polysaccharide Ameliorates Dextran Sulfate Sodium-Induced Colitis by Restoring the Intestinal Microbiota and Inhibiting the TLR4-NF-κB Axis.

Ulcerative colitis (UC) is a chronic intestinal ailment which cannot be completely cured. The occurrence of UC has been on the rise in recent years, which is highly detrimental to patients. The effectiveness of conventional drug treatment is limited. The long-term usage of these agents can lead to substantial adverse effects. Therefore, the development of a safe and efficient dietary supplement is important for the prevention of UC. Echinacea purpurea polysaccharide (EPP) is one of the main bioactive substances in Echinacea purpurea. EPP has many favorable effects, such as antioxidative, anti-inflammatory, and antitumor effects. However, whether EPP can prevent or alleviate UC is still unclear. This study aims to analyze the effect and mechanism of EPP on UC in mice using a 3% dextran sulfate sodium (DSS)-induced UC model. The results showed that dietary supplementation with 200 mg/kg EPP significantly alleviated the shortening of colon length, weight loss, and histopathological damage in DSS-induced colitis mice. Mechanistically, EPP significantly inhibits the activation of the TLR4/NF-κB pathway and preserves the intestinal mechanical barrier integrity by enhancing the expression of claudin-1, ZO-1, and occludin and reducing the loss of goblet cells. Additionally, 16S rRNA sequencing revealed that EPP intervention reduced the abundance of Bacteroides, Escherichia-Shigella, and Klebsiella; the abundance of Lactobacillus increased. The results of nontargeted metabonomics showed that EPP reshaped metabolism. In this study, we clarified the effect of EPP on UC, revealed the potential function of EPP, and supported the use of polysaccharide dietary supplements for UC prevention.

Huaier Polysaccharide Alleviates Dextran Sulphate Sodium Salt-Induced Colitis by Inhibiting Inflammation and Oxidative Stress, Maintaining the Intestinal Barrier, and Modulating Gut Microbiota.

The incidence of ulcerative colitis (UC) is increasing annually, and UC has a serious impact on patients' lives. Polysaccharides have gained attention as potential drug candidates for treating ulcerative colitis (UC) in recent years. Huaier (Trametes robiniophila Murr) is a fungus that has been used clinically for more than 1000 years, and its bioactive polysaccharide components have been reported to possess immunomodulatory effects, antitumour potential, and renoprotective effects. In this study, we aimed to examine the protective effects and mechanisms of Huaier polysaccharide (HP) against UC. Based on the H2O2-induced oxidative stress model in HT-29 cells and the dextran sulphate sodium salt (DSS)-induced UC model, we demonstrated that Huaier polysaccharides significantly alleviated DSS-induced colitis (weight loss, elevated disease activity index (DAI) scores, and colonic shortening). In addition, HP inhibited oxidative stress and inflammation and alleviated DSS-induced intestinal barrier damage. It also significantly promoted the expression of the mucin Muc2. Furthermore, HP reduced the abundance of harmful bacteria Escherichia-Shigella and promoted the abundance of beneficial bacteria Muribaculaceae_unclassified, Anaerotruncus, and Ruminococcaceae_unclassified to regulate the intestinal flora disturbance caused by DSS. Nontargeted metabolomics revealed that HP intervention would modulate metabolism by promoting levels of 3-hydroxybutyric acid, phosphatidylcholine (PC), and phosphatidylethanolamine (PE). These results demonstrated that HP had the ability to mitigate DSS-induced UC by suppressing oxidative stress and inflammation, maintaining the intestinal barrier, and modulating the intestinal flora. These findings will expand our knowledge of how HP functions and offer a theoretical foundation for using HP as a potential prebiotic to prevent UC.

An Improved Data Processing Algorithm for Spectrally Resolved Interferometry Using a Femtosecond Laser.

Spectrally resolved interferometry utilizing a femtosecond laser is widely employed for absolute distance measurement. However, deviations in the output time pulse of the conventional algorithm through inverse Fourier transform are inevitable. Herein, an improved data processing algorithm employing a time-shifting parameter is proposed to improve the accuracy of spectrally resolved interferometry. The principle of the proposed time-shifting algorithm is analyzed theoretically after clarifying the deviation source of the conventional algorithm. Simulation and experimental work were conducted to indicate the improvement in the accuracy of the output absolute distance. The results demonstrated that the proposed algorithm could reduce the deviation of output distances towards the reference values, reaching 0.58 µm by half compared to the conventional algorithm. Furthermore, the measurement uncertainty was evaluated using the Guide to the Expression of Uncertainty in Measurement (GUM), resulting in an expanded uncertainty of 0.71 µm with a 95% confidence.

Enantiospecific Analysis of Carboxylic Acids Using Cinchona Alkaloid Dimers as Chiral Solvating Agents.

Cinchona alkaloid derivatives as Brønsted base catalysts have attracted considerable attention in the field of asymmetric catalysis. However, their potential application as chiral solvating agents has not been described. In this research, we investigated the use of the Cinchona alkaloid dimer, namely, (DHQ)2PHAL, as a chiral solvating agent for discerning various mandelic acid derivatives through 1H NMR spectroscopy. The addition of catalytic amounts of DMAP facilitated this process. Our experimental results demonstrate that dimeric (DHQ)2PHAL exhibits remarkable chiral discrimination properties regarding the diagnostic split protons of 1H NMR signals (including 24 examples, up to 0.321 ppm). Furthermore, it serves as an excellent chiral discriminating agent and provides good resolution for racemic chiral phosphoric acid as determined by 31P NMR spectroscopy. The quality of enantiodifferentiation has also been evaluated by means of the parameter "resolution (Rs)". Significantly, this class of CSAs based on (alkaloid)2linker systems with an azaaromatic linker can be directly employed, which is commercially available in an enantiopure form at very low cost and exhibits promising potential in determining the enantiopurity of α-hydroxy acids by chemoselective and biocatalytic reactions.

The Brain's First "Traffic Map" through Unified Structural and Functional Connectivity (USFC) Modeling.

The brain's white matter connections are thought to provide the structural basis for its functional connections between distant brain regions but how our brain selects the best structural routes for effective functional communications remains poorly understood. In this study, we propose a Unified Structural and Functional Connectivity (USFC) model and use an "economical assumption" to create the brain's first "traffic map" reflecting how frequently each structural connection segment of the brain is used to achieve the global functional communication system. The resulting USFC map highlights regions in the subcortical, default-mode, and salience networks as the most heavily traversed nodes and a midline frontal-caudate-thalamus-posterior cingulate-visual cortex corridor as the backbone of the whole brain connectivity system. Our results further revealed a striking negative association between structural and functional connectivity strengths in routes supporting negative functional connections as well as much higher efficiency metrics in the USFC connectome when compared to structural and functional ones alone. Overall, the proposed USFC model opens up a new window for effective brain connectome modeling and provides a considerable leap forward in brain mapping efforts for a better understanding of the brain's fundamental communication mechanisms.

ScRNA-seq reveals novel immune-suppressive T cells and investigates CMV-TCR-T cells cytotoxicity against GBM.

BACKGROUND: Glioblastoma (GBM) is a fatal primary brain malignancy in adults. Previous studies have shown that cytomegalovirus (CMV) is a risk factor for tumorigenesis and aggressiveness for glioblastoma. However, little is known about how CMV infection affects immune cells in the tumor microenvironment of GBM. Furthermore, there has been almost no engineered T-cell receptor (TCR)-T targeting CMV for GBM research to date. METHODS: We evaluated the CMV infection status of patients with GBM's tumor tissue by immune electron microscopy, immunofluorescence, and droplet digital PCR. We performed single-cell RNA sequencing for CMV-infected GBM to investigate the effects of CMV on the GBM immune microenvironment. CellChat was applied to analyze the interaction between cells in the GBM tumor microenvironment. Additionally, we conducted single-cell TCR/B cell receptor (BCR) sequencing and Grouping of Lymphocyte Interactions with Paratope Hotspots 2 algorithms to acquire specific CMV-TCR sequences. Genetic engineering was used to introduce CMV-TCR into primary T cells derived from patients with CMV-infected GBM. Flow cytometry was used to measure the proportion and cytotoxicity status of T cells in vitro. RESULTS: We identified two novel immune cell subpopulations in CMV-infected GBM, which were bipositive CD68+SOX2+ tumor-associated macrophages and FXYD6+ T cells. We highlighted that the interaction between bipositive TAMs or cancer cells and T cells was predominantly focused on FXYD6+ T cells rather than regulatory T cells (Tregs), whereas, FXYD6+ T cells were further identified as a group of novel immunosuppressive T cells. CMV-TCR-T cells showed significant therapeutic effects on the human-derived orthotopic GBM mice model. CONCLUSIONS: These findings provided an insight into the underlying mechanism of CMV infection promoting the GBM immunosuppression, and provided a novel potential immunotherapy strategy for patients with GBM.

Profiles in neglect of older adult care workers in a long-term care facility: a latent profile analysis.

Background: Neglect is a common form of abuse, and long-term care facilities record higher incidences of this abuse. Given that older adult care workers are the main workforce in these facilities, their neglectful behavior requires public health attention. Internal individual characteristics can lead to older adult abuse, and managing workers who abuse older adults may require various methods. This study aimed to identify the profiles of neglect among older adult care workers in long-term care facilities and explore the influencing factors of neglect. Methods: In this cross-sectional study, a convenience sample of older adult care workers from 15 long-term care facilities in Shandong Province (N = 421) completed a questionnaire on the characteristics associated with neglect. Latent profile analysis was used to identify distinct neglect profiles and promote the understanding of individual characteristics associated with varying levels of neglect. One-way analysis of variance and multivariate logistic regression analyses were used to examine the population characteristic differences. Results: Older adult care workers exhibited three neglect profiles, namely, the "low-risk group," "medium-risk group," and "high-risk group." Males, participants with no employment qualification certificate, and those who did not attend regular training represented the majority of those in the "high-risk group." Participants with a monthly income of more than ¥ 4,000 and nursing 1-2 older adults simultaneously represented the majority of those in the "low-risk group." Conclusion: Long-term care facility administrators should tailor interventions to individual care worker profiles to reduce neglect behaviors and improve care levels.

Highly water-resistant paper via infiltration with polymeric microspheres from nanocellulose-stabilized plant oil-derived monomer.

Sustainable strategies to improve the water resistance of cellulose paper are actively sought. In this work, polymeric microspheres (PMs), prepared through emulsion polymerization of cellulose nanofibers stabilized rubber seed oil-derived monomer, were investigated as coatings on corrugated medium paper (CMP). After infiltrating porous paper with PMs, the water-resistant corrugated papers (WRCPn) with enhanced mechanical properties were obtained. When 30 wt% PMs were introduced, WRCP30 turned out to be highly compacted with an increased water contact angle of 106.3° and a low water vapor transmission rate of 81 g/(m2 d) at 23 °C. Meanwhile, the tensile strength of WRCP30 increased to 22.2 MPa, a 4-fold increase from CMP. When tested in a well-hydrated state, 71% of its mechanical strength in the dry state was maintained. Even with a low content of 10 wt% PMs, WRCP10 also exhibited stable tensile strength and water wettability during the cyclic soaking-drying process. Thus, the plant oil based sustainable emulsion polymers provide a convenient route for enhancing the overall performance of cellulose paper.