Transcriptomic analysis of the response of Avena sativa to Bacillus amyloliquefaciens DGL1.

Introduction: Bacillus amyloliquefaciens DGL1, isolated from the arid sandy areas in Dagler, Qinghai Province, China, promotes the growth of Avena sativa variety "Qing Yan 1". Methods: To elucidate the transcriptomic changes in the oat root system following interaction with DGL1 and to reveal the molecular mechanism by which DGL1 promotes oat growth, treatment and control groups of oat roots at 2, 4, 8, and 12 h after inoculation with a suspension of strain DGL1 were analyzed using Illumina high-throughput transcriptome sequencing technology. The differentially expressed genes were determined through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, and the metabolic pathways and key genes were analyzed. Results: The results showed that 7874, 13,392, 13,169, and 19,026 differentially expressed genes were significantly enriched in the glycolysis/gluconeogenesis pathway, amino acid metabolism, nitrogen metabolism, plant hormone signal transduction, and other related metabolic pathways in the oat roots at 2, 4, 8, and 12 h after inoculation with a DGL1 suspension. The GO and KEGG enrichment analyses revealed that the genes encoding plasma membrane ATPase, phosphoglycerate kinase gene PGK, ammonium transporter protein gene AMT, cellulose synthase gene CSLF6, and growth hormone response family gene IAA18 were significantly upregulated. Discussion: It is hypothesized that the pro-growth mechanism of strain DGL1 in oats is the result of the coordination of multiple pathways through the promotion of oat energy metabolism, phytohormone signaling, secondary metabolite synthesis, and amino acid metabolism.

Tumor Exosomal ENPP1 Hydrolyzes cGAMP to Inhibit cGAS-STING Signaling.

To evade immune surveillance, tumor cells express ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) on the surface of their membrane, which degrades extracellular cyclic GMP-AMP (cGAMP), thereby inhibiting the cyclic GMP-AMP synthase (cGAS) stimulator of interferon gene (STING) DNA-sensing pathway. To fully understand this tumor stealth mechanism, it is essential to determine whether other forms of ENPP1 with hydrolytic cGAMP activity also are present in the tumor microenvironment to regulate this innate immune pathway. Herein, it is reported that various tumor-derived exosomes carry ENPP1, and can hydrolyze synthetic 2'3'-cGAMP and endogenous 2'3'-cGAMP produced by cells to inhibit cGAS-STING pathway in immune cells. Moreover, tumor exosomal ENPP1 also can hydrolyze 2'3'-cGAMP bound to LL-37 (an effective transporter of 2'3'-cGAMP) to inhibit STING signaling. Furthermore, high expression of ENPP1 in exosomes is observed isolated from human breast and lung cancer tissue, and tumor exosomal ENPP1 inhibited the immune infiltration of CD8+ T cells and CD4+ T cells. The results elucidate the essential function of tumor exosomal ENPP1 in the cGAS-STING pathway, furthering understanding of the crosstalk between the tumor cells and immune system.

Community-embedded follow-up management intervention for geriatric primary care: a mixed-methods study of an integrated health services model.

BACKGROUND: To propose a community-embedded follow-up management model to provide health services for elderly patients with osteoporosis who live alone. METHODS: Researchers randomly selected 396 people with osteoporosis living alone from five communities in Nantong, China, for the study. These participants were randomly assigned to control and intervention groups. Twenty-four community physicians in five communities provided professional support based on a community-embedded follow-up management model. Participants completed quantitative questionnaires at baseline and after the 6-month follow-up intervention, and some participants underwent semi-structured face-to-face interviews. The primary outcome is the effectiveness of the community-embedded follow-up management model in improving the quality of life of elderly patients with osteoporosis living alone. Based on an objective quantitative assessment, the qualitative study explains and adds essential components of this community-based follow-up management model. RESULTS: The quantitative study showed that scores in physical functioning, ability to perform daily activities, self-efficacy, and mental status were significantly improved in the intervention group compared to the control group (p < 0.05). The most significant improvements were found in "mental status" (p = 0.012) and "self-care skills" (p = 0.003). The qualitative study reported the essential elements of a community healthcare model for older people living alone with osteoporosis, including professional support, personalized services, social support, and empowerment. CONCLUSIONS: Community-embedded follow-up management meets the need for elderly patients with osteoporosis living alone. It helps to improve health perception, promote physical and mental health, and optimize the quality of life in this population. Personalized services and professional support are two major contributing factors to effective embedded follow-up management in the community.

In Situ Detection of Nucleic Acids in Extracellular Vesicles via Membrane Fusion.

Extracellular vesicles (EVs) carry diverse biomolecules (e. g., nucleic acids, proteins) for intercellular communication, serving as important markers for diseases. Analyzing nucleic acids derived from EVs enables non-invasive disease diagnosis and prognosis evaluation. Membrane fusion, a fundamental cellular process wherein two lipid membranes merge, facilitates cell communication and cargo transport. Building on this natural phenomenon, recent years have witnessed the emergence of membrane fusion-based strategies for the detection of nucleic acids within EVs. These strategies entail the encapsulation of detection probes within either artificial or natural vesicles, followed by the induction of membrane fusion with EVs to deliver probes. This innovative approach not only enables in situ detection of nucleic acids within EVs but also ensures the maintenance of structural integrity of EVs, thus preventing nucleic acid degradation and minimizing the interference from free nucleic acids. This concept categorizes approaches into universal and targeted membrane fusion strategies, and discusses their application potential, and challenges and future prospects.

Nocardia rubra cell-wall skeleton mitigates whole abdominal irradiation-induced intestinal injury via regulating macrophage function.

Background: Ionizing radiation (IR)-induced intestinal injury is a major side effect and dose-limiting toxicity in patients receiving radiotherapy. There is an urgent need to identify an effective and safe radioprotectant to reduce radiation-induced intestinal injury. Immunoregulation is considered an effective strategy against IR-induced injury. The purpose of this article was to investigate the protective effect of Nocardia rubra cell wall skeleton (Nr-CWS), an immunomodulator, on radiation-induced intestinal damage and to explore its potential mechanism. Methods: C57BL/6 J male mice exposed to 12 Gy whole abdominal irradiation (WAI) were examined for survival rate, morphology and function of the intestine and spleen, as well as the gut microbiota, to comprehensively evaluate the therapeutic effects of Nr-CWS on radiation-induced intestinal and splenetic injury. To further elucidate the underlying mechanisms of Nr-CWS-mediated intestinal protection, macrophages were depleted by clodronate liposomes to determine whether Nr-CWS-induced radioprotection is macrophage dependent, and the function of peritoneal macrophages stimulated by Nr-CWS was detected in vitro. Results: Our data showed that Nr-CWS promoted the recovery of intestinal barrier function, enhanced leucine-rich repeat-containing G protein-coupled receptor 5+ intestinal stem cell survival and the regeneration of intestinal epithelial cells, maintained intestinal flora homeostasis, protected spleen morphology and function, and improved the outcome of mice exposed to 12 Gy WAI. Mechanistic studies indicated that Nr-CWS recruited macrophages to reduce WAI-induced intestinal damage. Moreover, macrophage depletion by clodronate liposomes blocked Nr-CWS-induced radioprotection. In vitro, we found that Nr-CWS activated the nuclear factor kappa-B signaling pathway and promoted the phagocytosis and migration ability of peritoneal macrophages. Conclusions: Our study suggests the therapeutic effect of Nr-CWS on radiation-induced intestinal injury, and provides possible therapeutic strategy and potential preventive and therapeutic drugs to alleviate it.

[Multi-Voiced Narrative of Home-Based Palliative Care:Report of One Case].

Terminally ill patients face multiple difficulties in home care.Home-based palliative care adhering to the concept of whole-person,whole-family,whole-team,and whole-course care is able to meet the needs of terminally ill patients and their families.In this paper,we reported the care history and home-based palliative care process of a patient with end-stage breast tumor and summarized the experience,aiming to provide reference for the future work of home-based palliative care.

Influence of parental education on the intelligence quotient profiles and socially adaptive behavior of school-age children with autism spectrum disorder in eastern China. / 父母教育水平对中国东部地区孤独症谱系障碍学龄儿童智力及社会适应行为的影响.

Intelligence quotient (IQ) and adaptive behavior are the influencing factors of autism spectrum disorder (ASD) in children entering mainstream schools. This study explored the association between parental education level, IQ, and adaptive behavior in ASD groups. A total of 257 school-age ASD children were enrolled in our study from January 2017 to June 2021. Their parents completed a standard demographic form, including age at autism diagnosis, gender, school placement, and parents' educational background. The Chinese version of the Wechsler Intelligence Scale for Children, Fourth Edition (WISC-IV) was completed by a certified assessor for each enrolled child. Parents were interviewed on adaptive behavior using the Chinese version of the Adaptive Behavior Assessment System, Second Edition (ABAS-II). The average IQ of school-age ASD children was 76.88 (standard deviation (SD)=22.62) and boys had higher IQ levels than girls. The IQ was positively correlated with age. The General Adaptive Composite (GAC) score was 82.47 (SD=15.86) and adaptive behavior did not increase with age. ASD children who attended mainstream schools had better adaptive behavior profiles than other children. The mother's education level showed a significant correlation with the IQ and adaptive behavior of autistic children, while the father's education level did not. Consequently, better training and support for parents may help autistic children enter mainstream schools, with adaptive training being the most urgently required skill for parents.

Glaucoma drainage device implantation and cyclophotocoagulation in the management of refractory glaucoma after Descemet-stripping automated endothelial keratoplasty.

AIM: To compare the surgical outcomes of glaucoma drainage device implantation (GDI) and trans-scleral neodymium:YAG cyclophotocoagulation (CPC) in the management of refractory glaucoma after Descemet-stripping automated endothelial keratoplasty (DSAEK). METHODS: This retrospective study on observational case series enrolled 29 patients who underwent DSAEK and posterior anti-glaucoma surgery (15 with GDI and 14 with CPC). The main outcome measures were intraocular pressure (IOP), glaucoma surgery success rate (defined as IOP of 6-21 mm Hg without additional anti-glaucoma operation), number of glaucoma medications, endothelial graft status, and best-corrected visual acuity (BCVA). RESULTS: The mean follow-up time was 34.1 and 21.0mo for DSAEK or glaucoma surgeries, both for the GDI and CPC groups. Both groups showed significant IOP reduction after glaucoma surgery. The GDI group presented a significantly higher success rate in IOP control than the CPC group (60% vs 21.4%, P=0.03). Both procedures significantly decreased the number of glaucoma medications (P=0.03). Forty percent and 57% of cases in the GDI and the CPC group, respectively, experienced endothelial graft failure during follow-up (P=0.36). Significantly worse BCVA after surgery was observed in the CPC group but not in the GDI group. CONCLUSION: Both GDI and CPC significantly decrease IOP in eyes with glaucoma after DSAEK. GDI is preferable to CPC in refractory glaucoma cases after DSAEK, as it manifests a significantly higher success rate for IOP control, similar endothelial graft failure rate, and relatively preserves BCVA than CPC.

The Diverse Mycorrizal Morphology of Rhododendron dauricum, the Fungal Communities Structure and Dynamics from the Mycorrhizosphere.

It is generally believed that mycorrhiza is a microecosystem composed of mycorrhizal fungi, host plants and other microscopic organisms. The mycorrhiza of Rhododendron dauricum is more complex and the diverse morphology of our investigated results displays both typical ericoid mycorrhizal characteristics and ectomycorrhizal traits. The characteristics of ectendoomycorrhiza, where mycelial invade from the outside into the root cells, have also been observed. In order to further clarify the mycorrhizal fungi members and other fungal communities of R. dauricum mycorrhiza, and explore the effects of vegetation and soil biological factors on their community structure, we selected two woodlands in the northeast of China as samples-one is a mixed forest of R. dauricum and Quercus mongolica, and the other a mixed forest of R. dauricum, Q. mongolica, and Pinus densiflor. The sampling time was during the local growing season, from June to September. High-throughput sequencing yielded a total of 3020 fungal amplicon sequence variants (ASVs), which were based on sequencing of the internal transcribed spacer ribosomal RNA (ITS rRNA) via the Illumina NovaSeq platform. In the different habitats of R. dauricum, there are differences in the diversity of fungi obtained from mycorrhizal niches, and specifically the mycorrhizal fungal community structure in the complex vegetation of mixed forests, where R. dauricum is found, exhibits greater stability, with relatively minor changes over time. Soil fungi are identified as the primary source of fungi within the mycorrhizal niche, and the abundance of mycorrhizal fungi from mycorrhizal niches in R. dauricum is significantly influenced by soil pH, organic matter, and available nitrogen. The relationship between soil fungi and mycorrhizal fungi from mycorrhizal niches is simultaneously found to be intricate, while the genus Hydnellum emerges as a central genus among mycorrhizal fungi from mycorrhizal niches. However, there is currently a substantial gap in the foundational research of this genus, including the fact that mycorrhizal fungi from mycorrhizal niches have, compared to fungi present in the soil, proven to be more sensitive to changes in soil moisture.

Cell-intrinsic PD-L1 ablation sustains effector CD8+ T cell responses and promotes antitumor T cell therapy.

Adoptive cell therapies are emerging forms of immunotherapy that reprogram T cells for enhanced antitumor responses. Although surface programmed cell death-ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) engagement inhibits antitumor immunity, the role of cell-intrinsic PD-L1 in adoptive T cell therapy remains unknown. Here, we found that intracellular PD-L1 was enriched in tumor-infiltrating CD8+ T cells of cancer patients. PD-L1 ablation promoted antitumor immune responses and the maintenance of an effector-like state of therapeutic CD8+ T cells, while blockade of surface PD-L1 was unable to impact on their expansion and function. Moreover, cell-intrinsic PD-L1 impeded CD8+ T cell activity, which partially relied on mTORC1 signaling. Furthermore, endogenous tumor-reactive CD8+ T cells were motivated by BATF3-driven dendritic cells after adoptive transfer of PD-L1-deficient therapeutic CD8+ T cells. This role of cell-intrinsic PD-L1 in therapeutic CD8+ T cell dysfunction highlights that disrupting cell-intrinsic PD-L1 in CD8+ T cells represents a viable approach to improving T cell-based cancer immunotherapy.

The Effect and Mechanism of Fufang Banbianlian Injection in the Treatment of Mesangial Proliferative Glomerulonephritis.

OBJECTIVE: Mesangial proliferative glomerulonephritis (MsPGN) is an important cause of chronic kidney disease. Abnormal proliferation of mesangial cells and immune-inflammatory response are its important pathological manifestations. Currently, there is no ideal treatment for this disease. Fufang Banbianlian Injection (FBI) has anti-inflammatory, antioxidant, and immuneenhancing effects, and is mostly used for the treatment of bronchitis, pneumonia, and respiratory tract infections in children. METHODS: A rat model of MsPGN was established and treated with FBI. The efficacy was tested through pathological experiments and urine protein quantification. Network pharmacology methods were used to predict the signaling pathways and key proteins that exert the efficacy of FBI, and were screened through molecular docking experiments. The active substances that work were verified through cell experiments. RESULTS: The results confirmed that intervention with FBI can inhibit the proliferation of glomerular cells and reduce the infiltration of macrophages, thereby reducing the pathological damage of rats with mesangial proliferative nephritis; it has been found to have an obvious therapeutic effect. Molecular docking results have shown kaempferol (Kae), the main component of FBI, to have a good affinity for key targets. The results of in vitro verification experiments showed that FBI and its active ingredient Kae may play a therapeutic role by regulating the NF-κB signaling pathway in mesangial cells, inhibiting its activation and the secretion of proinflammatory cytokines. CONCLUSION: Through network pharmacology, molecular docking, and experimental verification, it was confirmed that FBI and its active ingredient Kae can reduce the molecular mechanism of pathological damage of MsPGN by regulating the NF-κB signaling pathway and providing potential therapeutic drugs for the treatment of this disease.

Decoder-seq enhances mRNA capture efficiency in spatial RNA sequencing.

Spatial transcriptomics technologies with high resolution often lack high sensitivity in mRNA detection. Here we report a dendrimeric DNA coordinate barcoding design for spatial RNA sequencing (Decoder-seq), which offers both high sensitivity and high resolution. Decoder-seq combines dendrimeric nanosubstrates with microfluidic coordinate barcoding to generate spatial arrays with a DNA density approximately ten times higher than previously reported methods while maintaining flexibility in resolution. We show that the high RNA capture efficiency of Decoder-seq improved the detection of lowly expressed olfactory receptor (Olfr) genes in mouse olfactory bulbs and contributed to the discovery of a unique layer enrichment pattern for two Olfr genes. The near-cellular resolution provided by Decoder-seq has enabled the construction of a spatial single-cell atlas of the mouse hippocampus, revealing dendrite-enriched mRNAs in neurons. When applying Decoder-seq to human renal cell carcinomas, we dissected the heterogeneous tumor microenvironment across different cancer subtypes and identified spatial gradient-expressed genes related to epithelial-mesenchymal transition with the potential to predict tumor prognosis and progression.

The efficacy of platelet rich plasma on women with poor ovarian response: a systematic review and meta-analysis.

BACKGROUND: Platelet-rich plasma (PRP) is a therapeutic approach that is gaining attention for its potential in the treatment of poor ovarian response. This meta-analysis aimed to systematically review and analyze clinical studies to evaluate the impact of PRP on poor responders undergoing ovarian stimulation for IVF. METHODS: A comprehensive search was conducted in electronic databases, including PubMed, Embase, Scopus, Web of Science, and the Cochrane Library to identify relevant studies published in English. The pooled data, such as pregnancy outcome, number of MII oocytes, number of transferable embryos, and ovarian reserve markers were analyzed using R version 4.2.3. RESULTS: A total of 10 trials were enrolled in the present meta-analysis. Following PRP treatment, live birth rate was found to be 16.6% (95% CI 8.8%-26.1%), while clinical pregnancy rate was observed to be 25.4% (95% CI 13.1%-39.9%). PRP pretreatment resulted in a higher number of MII oocytes (MD 1.073, 95% CI 0.720 to 1.427), a higher number of embryos (MD 0.946, 95% CI 0.569 to 1.323), a higher antral follicle count (MD 1.117; 95% CI 0.689 to 1.544), and the change of hormone levels. CONCLUSIONS: Among the studies evaluated in this review, PRP showed promising results in poor responder. Further research is required to clarify the potential role of PRP in female reproductive health.

What is the context? The incidence of poor ovarian response following ovarian stimulation ranges globally from 5.6% to 35.1%.Although various interventions have been implemented in patients with POR, there is a lack of empirical evidence demonstrating the superiority of any of these therapies over one another.Platelet-rich plasma, which is rich in growth factors that have been implicated in cellular growth, differentiation, angiogenesis, and tissue repair, is emerging as a promising therapeutic modality.Limited data determines the viability of PRP as an alternative therapy for POR patients, but further evidence is needed to quantify this effect.What is new? To the best of our knowledge, this is the first systematic review and meta-analysis that investigated the efficacy of PRP on women with POR, including ten trials and 876 patients.This review provides a comprehensive overview of the existing evidence on the utilization of PRP in poor responders, while also emphasizing the primary limitations in the literature and the necessity for future research based on evidence.What is the impact? Among the studies evaluated in this review, PRP showed a potential positive impact on the regulation of sex hormone levels, ovarian response, and pregnancy outcomes.

Serum levels of sonic hedgehog in patients with IgA nephropathy are closely associated with intrarenal arteriolar lesions.

BACKGROUND: Intrarenal arteriolar disease is a major risk factor for poor prognosis in immunoglobulin A nephropathy (IgAN). The morphologic factor sonic hedgehog (SHH) plays an important role in a variety of vascular diseases, so it may be directly or indirectly involved in the process of renal arteriolar disease. The purpose of this study was to investigate the correlation between serum SHH levels and renal arteriole disease in patients with IgAN. METHODS: Subjects with primary IgAN diagnosed by renal biopsy performed between October 2018 and August 2019 at the First Medical Center of the Chinese PLA General Hospital were recruited. Blood specimens were collected from the patients within 1 week before renal biopsy after they signed an informed consent form, and healthy controls were recruited for blood specimen collection during the same period. The concentration of serum SHH was measured by enzyme-linked immunosorbent assay in this population. RESULTS: Serum SHH levels were significantly lower in the IgAN group than in the control group. 41 of the 94 subjects diagnosed with IgAN had severe renal arteriolosclerosis and, compared to their less severely affected counterparts, were older, more hypertensive, and characterized by lower levels of SHH, higher levels of tubular atrophy/interstitial fibrosis and a higher Lee's classification. Serum SHH concentration was found to be an independent predictor of severe intrarenal arteriolosclerosis in IgAN subjects after correction using multivariate analysis. CONCLUSION: In this study, serum SHH levels were found to be significantly lower in patients with IgAN than in healthy subjects. Serum SHH may serve as a noninvasive biomarker of intrarenal arteriolosclerosis in patients with IgAN.

Circulating T-cell subsets discrepancy between bipolar disorder and major depressive disorder during mood episodes: A naturalistic, retrospective study of 1015 cases.

AIMS: We aimed to investigate whether peripheral T-cell subsets could be a biomarker to distinguish major depressive disorder (MDD) and bipolar disorder (BD). METHODS: Medical records of hospitalized patients in the Department of Psychiatry, the First Affiliated Hospital, Zhejiang University School of Medicine, from January 2015 to September 2020 with a discharge diagnosis of MDD or BD were reviewed. Patients who underwent peripheral blood examination of T-cell subtype proportions, including CD3+, CD4+, CD8+ T-cell, and natural killer (NK) cells, were enrolled. The Chi-square test, t-test, or one-way analysis of variance were used to analyze group differences. Demographic profiles and T-cell data were used to construct a random forest classifier-based diagnostic model. RESULTS: Totally, 98 cases of BD mania, 459 cases of BD depression (BD-D), and 458 cases of MDD were included. There were significant differences in the proportions of CD3+, CD4+, CD8+ T-cell, and NK cells among the three groups. Compared with MDD, the BD-D group showed higher CD8+ but lower CD4+ T-cell and a significantly lower ratio of CD4+ and CD8+ proportions. The random forest model achieved an area under the curve of 0.77 (95% confidence interval: 0.71-0.83) to distinguish BD-D from MDD patients. CONCLUSION: These findings imply that BD and MDD patients may harbor different T-cell inflammatory patterns, which could be a potential diagnostic biomarker for mood disorders.

Pyruvate kinase M2 regulates kidney fibrosis through pericyte glycolysis during the progression from acute kidney injury to chronic kidney disease.

We aimed to investigate the role of renal pericyte pyruvate kinase M2 (PKM2) in the progression of acute kidney injury (AKI) to chronic kidney disease (CKD). The role of PKM2 in renal pericyte-myofibroblast transdifferentiation was investigated in an AKI-CKD mouse model. Platelet growth factor receptor beta (PDGFRß)-iCreERT2; tdTomato mice were used for renal pericyte tracing. Western blotting and immunofluorescence staining were used to examine protein expression. An 5-ethynyl-2'-deoxyuridine assay was used to measure renal pericyte proliferation. A scratch cell migration assay was used to analyse cell migration. Seahorse experiments were used to examine glycolytic rates. Enzyme-linked immunoassay was used to measure pyruvate kinase enzymatic activity and lactate concentrations. The PKM2 nuclear translocation inhibitors Shikonin and TEPP-46 were used to alter pericyte transdifferentiation. In AKI-CKD, renal pericytes proliferated and transdifferentiated into myofibroblasts and PKM2 is highly expressed in renal pericytes. Shikonin and TEPP-46 inhibited pericyte proliferation, migration, and pericyte-myofibroblast transdifferentiation by reducing nuclear PKM2 entry. In the nucleus, PKM2 promoted downstream lactate dehydrogenase A (LDHA) and glucose transporter 1 (GLUT1) transcription, which are critical for glycolysis. Therefore, PKM2 regulates pericyte glycolytic and lactate production, which regulates renal pericyte-myofibroblast transdifferentiation. PKM2-regulated renal pericyte-myofibroblast transdifferentiation by regulating downstream LDHA and GLUT1 transcription and lactate production. Reducing nuclear PKM2 import can reduce renal pericytes-myofibroblasts transdifferentiation, providing new ideas for AKI-CKD treatment.

Mechanical Metamaterials for Handwritten Digits Recognition.

The increasing needs for new types of computing lie in the requirements in harsh environments. In this study, the successful development of a non-electrical neural network is presented that functions based on mechanical computing. By overcoming the challenges of low mechanical signal transmission efficiency and intricate layout design methodologies, a mechanical neural network based on bistable kirigami-based mechanical metamaterials have designed. In preliminary tests, the system exhibits high reliability in recognizing handwritten digits and proves operable in low-temperature environments. This work paves the way for a new, alternative computing system with broad applications in areas where electricity is not accessible. By integrating with the traditional electronic computers, the present system lays the foundation for a more diversified form of computing.

Noncanonical MAVS signaling restrains dendritic cell-driven antitumor immunity by inhibiting IL-12.

Mitochondrial antiviral signaling protein (MAVS)-mediated cytosolic RNA sensing plays a central role in tumor immunogenicity. However, the effects of host MAVS signaling on antitumor immunity remain unclear. Here, we demonstrate that the host MAVS pathway supports tumor growth and impairs antitumor immunity, whereas MAVS deficiency in dendritic cells (DCs) promotes tumor-reactive CD8+ T cell responses. Specifically, CD8+ T cell priming capacity was enhanced by MAVS ablation in a type I interferon-independent, but IL-12-dependent, manner. Mechanistically, loss of the RIG-I/MAVS cascade activated the noncanonical NF-κB pathway and in turn induced IL-12 production by DCs. MAVS-restrained IL-12 promoted cross-talk between CD8+ T cells and DCs, which was licensed by IFN-γ. Moreover, ablation of host MAVS sensitized tumors to immunotherapy and attenuated radiation resistance, thereby facilitating the maintenance of effector CD8+ T cells. These findings demonstrate that the host MAVS pathway acts as an immune regulator of DC-driven antitumor immunity and support the development of immunotherapies that antagonize MAVS signaling in DCs.

Exploring the needs and coping strategies of family caregivers taking care of dying patients at home: a field study.

BACKGROUND: Most Chinese patients chose to die at home, therefore there is a reliance on the family caregivers to be involved in their palliative care. The needs and coping strategies of family caregivers in home-based palliative care are rooted in culture. Little is known about the needs and coping strategies of family caregivers taking care of dying patients at home. METHODS: A field study using semi-structured interview, participant observation, documents and records collection was employed. The study was conducted in two palliative care outpatient departments in tertiary hospitals and four communities in Beijing, China from March 2021 to July 2022. Using purposive sampling, twenty-five family caregivers were recruited. All collected data were analyzed using content analysis approach. RESULTS: Five themes emerged, including three care needs and two coping strategies. Family caregivers need to learn care skills and acquire care resources, including (i) decision-making about home-based palliative care, (ii) improving patient's quality of life, and (iii) signs of final hours and funeral procedures. In facing the care burden, family caregivers coped by (iv) balancing the roles of caregivers and individuals: giving priority to patient care while maintaining their own normal life. In facing the death of a loved one, family caregivers responded by (v) making room for coming death by facing death indirectly and "rescuing" patients for consolation while preparing for the coming death. CONCLUSION: Family caregivers strive to balance the roles of being caregivers and being themselves. As caregivers, they actively prepare patients for good death with no regrets. As individuals, they preserve themselves from being hurt to maintain normal life. The needs of family caregivers focus on caregiver role and are manifested in care skills and resources. TRIAL REGISTRATION: Not registered.