Upgrading pectin methylation for consistently enhanced biomass enzymatic saccharification and cadmium phytoremediation in rice Ospmes site-mutants.

Crop straws provide enormous biomass residues applicable for biofuel production and trace metal phytoremediation. However, as lignocellulose recalcitrance determines a costly process with potential secondary waste liberation, genetic modification of plant cell walls is deemed as a promising solution. Although pectin methylation plays an important role for plant cell wall construction and integrity, little is known about its regulation roles on lignocellulose hydrolysis and trace metal elimination. In this study, we initially performed a typical CRISPR/Cas9 gene-editing for site mutations of OsPME31, OsPME34 and OsPME79 in rice, and then determined significantly upgraded pectin methylation degrees in the young seedlings of three distinct site-mutants compared to their wild type. We then examined distinctively improved lignocellulose recalcitrance in three mutants including reduced cellulose levels, crystallinity and polymerization or raised hemicellulose deposition and cellulose accessibility, which led to specifically enlarged biomass porosity either for consistently enhanced biomass enzymatic saccharification under mild alkali pretreatments or for cadmium (Cd) accumulation up to 2.4-fold. Therefore, this study proposed a novel model to elucidate how pectin methylation could play a unique enhancement role for both lignocellulose enzymatic hydrolysis and Cd phytoremediation, providing insights into precise pectin modification for effective biomass utilization and efficient trace metal exclusion.

Rosuvastatin Enhances Lymphangiogenesis after Myocardial Infarction by Regulating the miRNAs/Vascular Endothelial Growth Factor Receptor 3 (miRNAs/VEGFR3) Pathway.

BACKGROUND: Several clinical studies have suggested that the early administration of statins could reduce the risk of in-hospital mortality in acute myocardial infarction (AMI) patients. Recently, some studies have identified that stimulating lymphangiogenesis after AMI could improve cardiac function by reducing myocardial edema and inflammation. This study aimed to identify the effect of rosuvastatin on postinfarct lymphangiogenesis and to identify the underlying mechanism of this effect. METHOD: Myocardial infarction (MI) was induced by ligation of the left anterior descending coronary artery in mice orally administered rosuvastatin for 7 days. The changes in cardiac function, pathology, and lymphangiogenesis following MI were measured by echocardiography and immunostaining. EdU, Matrigel tube formation, and scratch wound assays were used to evaluate the effect of rosuvastatin on the proliferation, tube formation, and migration of the lymphatic endothelial cell line SVEC4-10. The expression of miR-107-3p, miR-491-5p, and VEGFR3 was measured by polymerase chain reaction (PCR) and Western blotting. A gain-of-function study was performed using miR-107-3p and miR-491-5p mimics. RESULTS: The rosuvastatin-treated mice had a significantly improved ejection fraction and increased lymphatic plexus density 7 days after MI. Rosuvastatin also reduced myocardial edema and inflammatory response after MI. We used a VEGFR3 inhibitor to partially reverse these effects. Rosuvastatin promoted the proliferation, migration, and tube formation of SVEC4-10 cells. PCR and Western blot analyses revealed that rosuvastatin intervention downregulated miR-107-3p and miR-491-5p and promoted VEGFR3 expression. The gain-of-function study showed that miR-107-3p and miR-491-5p could inhibit the proliferation, migration, and tube formation of SVEC4-10 cells. CONCLUSION: Rosuvastatin could improve heart function by promoting lymphangiogenesis after MI by regulating the miRNAs/VEGFR3 pathway.

Vascular complications of diabetes: A narrative review.

Diabetes mellitus is a complex chronic metabolic disease characterized by hyperglycemia and various complications. According to the different pathophysiological mechanisms, these complications can be classified as microvascular or macrovascular complications, which have long-term negative effects on vital organs such as the eyes, kidneys, heart, and brain, and lead to increased patient mortality. Diabetes mellitus is a major global health issue, and its incidence and prevalence have increased significantly in recent years. Moreover, the incidence is expected to continue to rise as more people adopt a Western lifestyle and diet. Thus, it is essential to understand the epidemiology, pathogenesis, risk factors, and treatment of vascular complications to aid patients in managing the disease effectively. This paper provides a comprehensive review of the literature to clarify the above content. Furthermore, this paper also delves into the correlation between novel risk factors, such as long noncoding RNAs, gut microbiota, and nonalcoholic fatty liver disease, with diabetic vascular complications.

Effectiveness of Home-Based Telerehabilitation Interventions for Dysphagia in Patients With Head and Neck Cancer: Systematic Review.

BACKGROUND: Multimodal treatment-induced dysphagia has serious negative effects on survivors of head and neck cancer. Owing to advances in communication technologies, several studies have applied telecommunication-based interventions that incorporate swallowing exercises, education, monitoring, feedback, self-management, and communication. It is especially urgent to implement home-based remote rehabilitation in the context of the COVID-19 pandemic. However, the optimal strategy and effectiveness of remote interventions are unclear. OBJECTIVE: This systematic review aimed to examine the evidence regarding the efficacy of telerehabilitation for reducing physiological and functional impairments related to swallowing and for improving adherence and related influencing factors among head and neck cancer survivors. METHODS: The PubMed, MEDLINE, CINAHL, Embase, and Cochrane Library databases were systematically searched up to July 2023 to identify relevant articles. In total, 2 investigators independently extracted the data and assessed the methodological quality of the included studies using the quality assessment tool of the Joanna Briggs Institute. RESULTS: A total of 1465 articles were initially identified; ultimately, 13 (0.89%) were included in the systematic review. The quality assessment indicated that the included studies were of moderate to good quality. The results showed that home-based telerehabilitation improved the safety of swallowing and oral feeding, nutritional status, and swallowing-related quality of life; reduced negative emotions; improved swallowing rehabilitation adherence; was rated by participants as highly satisfactory and supportive; and was cost-effective. In addition, this review investigated factors that influenced the efficacy of telerehabilitation, which included striking a balance among swallowing training strategy, intensity, frequency, duration, and individual motor ability; treating side effects of radiotherapy; providing access to medical, motivational, and educational information; providing feedback on training; providing communication and support from speech pathologists, families, and other survivors; and addressing technical problems. CONCLUSIONS: Home-based telerehabilitation has shown great potential in reducing the safety risks of swallowing and oral feeding, improving quality of life and adherence, and meeting information needs for dysphagia among survivors of head and neck cancer. However, this review highlights limitations in the current literature, and the current research is in its infancy. In addition, owing to the diversity of patient sociodemographic, medical, physiological and functional swallowing, and behavioral factors, we recommend the development of tailored telemedicine interventions to achieve the best rehabilitation effects with the fewest and most precise interventions.

Gut microbiota in children with split-dose bowel preparations revealed by metagenomics.

Objective: Split-dose polyethylene glycol (PEG) is routinely used for bowel preparation before colonoscopy. This study aimed to investigate the composition of gut microbiota and its functions in pediatric patients undergoing split-dose PEG bowel preparation for colonoscopy to understand the stability and resilience of gut microbiota. Material and methods: From September to December 2021, 19 pediatric patients were enrolled at Shenzhen Children's Hospital and 76 samples (4 time points) were analyzed using metagenomics. Time points included Time_1 (one day before bowel preparation), Time_2 (one day after colonoscopy), Time_3 (two weeks after bowel preparation), and Time_4 (four weeks after bowel preparation). Result: Alpha diversity comparison at both the species and gene levels showed a decrease in community richness after colonoscopy, with little statistical significance. However, the Shannon diversity index significantly decreased (P<0.05) and gradually returned to pre-preparation levels at two weeks after bowel preparation. The genus level analysis showed six genera (Eubacterium, Escherichia, Intertinibacter, Veillonella, Ruminococcaceae unclassified, and Coprobacillus) significantly different across the four time periods. Additionally, at the species level, the abundance of Escherichia coli, Bacteroides fragilis, and Veillonella parvula significantly increased at one day after colonoscopy before gradually decreasing at two weeks after bowel preparation. In contrast, the abundance of Intertinibacter bartlettii decreased at one day after colonoscopy but then recovered at two weeks after bowel preparation, reaching the preoperative level at four weeks after bowel preparation. Furthermore, five functional pathways (base excision repair, biosynthesis of ansamycins, biosynthesis of siderophore group nonribosomal peptide, flavonoid biosynthesis, and biosynthesis of type II polyketide products) were significantly different across the four time periods, with recovery at two weeks after bowel preparation and reaching preoperative levels at four weeks after bowel preparation. Conclusions: Gut microbiota at the genus level, species level, and functional pathways are impacted in pediatric patients undergoing split-dose PEG bowel preparation and colonoscopy, with recovery two weeks following bowel preparation. However, the phylum level was not impacted. Modifications in gut microbiota composition and function may be investigated in future studies of bowel preparation. This study highlights the stability and resilience of gut microbiota among pediatric patients during bowel preparation.

Thermosensitive SUMOylation of TaHsfA1 defines a dynamic ON/OFF molecular switch for the heat stress response in wheat.

Dissecting genetic components in crop plants associated with heat stress (HS) sensing and adaptation will facilitate the design of modern crop varieties with improved thermotolerance. However, the molecular mechanisms underlying the ON/OFF switch controlling HS responses (HSRs) in wheat (Triticum aestivum) remain largely unknown. In this study, we focused on the molecular action of TaHsfA1, a class A heat shock transcription factor, in sensing dynamically changing HS signals and regulating HSRs. We show that the TaHsfA1 protein is modified by small ubiquitin-related modifier (SUMO) and that this modification is essential for the full transcriptional activation activity of TaHsfA1 in triggering downstream gene expression. During sustained heat exposure, the SUMOylation of TaHsfA1 is suppressed, which partially reduces TaHsfA1 protein activity, thereby reducing the intensity of downstream HSRs. In addition, we demonstrate that TaHsfA1 interacts with the histone acetyltransferase TaHAG1 in a thermosensitive manner. Together, our findings emphasize the importance of TaHsfA1 in thermotolerance in wheat. In addition, they define a highly dynamic SUMOylation-dependent "ON/OFF" molecular switch that senses temperature signals and contributes to thermotolerance in crops.

Response of Juvenile Saccharina japonica to the Combined Stressors of Elevated pCO2 and Excess Copper.

Coastal macroalgae may be subjected to global and local environmental stressors, such as ocean acidification and heavy-metal pollution. We investigated the growth, photosynthetic characteristics, and biochemical compositions of juvenile sporophytes of Saccharina japonica cultivated at two pCO2 levels (400 and 1000 ppmv) and four copper concentrations (natural seawater, control; 0.2 µM, low level; 0.5 µM, medium level; and 1 µM, high level) to better understand how macroalgae respond to ongoing environmental changes. The results showed that the responses of juvenile S. japonica to copper concentrations depended on the pCO2 level. Under the 400 ppmv condition, medium and high copper concentrations significantly decreased the relative growth rate (RGR) and non-photochemical quenching (NPQ) but increased the relative electron transfer rate (rETR) and chlorophyll a (Chl a), chlorophyll c (Chl c), carotenoid (Car), and soluble carbohydrate contents. At 1000 ppmv, however, none of the parameters had significant differences between the different copper concentrations. Our data suggest that excess copper may inhibit the growth of juvenile sporophytes of S. japonica, but this negative effect could be alleviated by CO2-induced ocean acidification.

The autism spectrum among transgender youth: default mode functional connectivity.

The common intersection of autism and transgender identities has been described in clinical and community contexts. This study investigates autism-related neurophenotypes among transgender youth. Forty-five transgender youth, evenly balanced across non-autistic, slightly subclinically autistic, and full-criteria autistic subgroupings, completed resting-state functional magnetic resonance imaging to examine functional connectivity. Results confirmed hypothesized default mode network (DMN) hub hyperconnectivity with visual and motor networks in autism, partially replicating previous studies comparing cisgender autistic and non-autistic adolescents. The slightly subclinically autistic group differed from both non-autistic and full-criteria autistic groups in DMN hub connectivity to ventral attention and sensorimotor networks, falling between non-autistic and full-criteria autistic groups. Autism traits showed a similar pattern to autism-related group analytics, and also related to hyperconnectivity between DMN hub and dorsal attention network. Internalizing, gender dysphoria, and gender minority-related stigma did not show connectivity differences. Connectivity differences within DMN followed previously reported patterns by designated sex at birth (i.e. female birth designation showing greater within-DMN connectivity). Overall, findings suggest behavioral diagnostics and autism traits in transgender youth correspond to observable differences in DMN hub connectivity. Further, this study reveals novel neurophenotypic characteristics associated with slightly subthreshold autism, highlighting the importance of research attention to this group.

Cingulate-Prefrontal Connectivity During Dynamic Cognitive Control Mediates Association Between p Factor and Adaptive Functioning in a Transdiagnostic Pediatric Sample.

BACKGROUND: Covariation among psychiatric symptoms is being actively pursued for transdiagnostic dimensions of psychopathology with predictive utility. A superordinate dimension, the p factor, reflects overall psychopathology burden and has support from genetic and neuroimaging correlates. However, the neurocognitive correlates that link an elevated p factor to maladaptive outcomes are unknown. We tested the mediating potential of dynamic adjustments in cognitive control rooted in functional connections anchored by the dorsal anterior cingulate cortex (dACC) in a transdiagnostic pediatric sample. METHODS: A multiple mediation model tested the association between the p factor (derived by principal component analysis of Child Behavior Checklist syndrome scales) and outcome measured with the Vineland Adaptive Behavior Scale-II in 89 children ages 8 to 13 years (23 female) with a variety of primary neurodevelopmental diagnoses who underwent functional magnetic resonance imaging during a socioaffective Stroop-like task with eye gaze as distractor. Mediators included functional connectivity of frontoparietal- and salience network-affiliated dACC seeds during conflict adaptation. RESULTS: Higher p factor scores were related to worse adaptive functioning. This effect was partially mediated by conflict adaptation-dependent functional connectivity between the frontoparietal network-affiliated dACC seed and the right dorsolateral prefrontal cortex. Post hoc follow-up indicated that the p factor was related to all Vineland Adaptive Behaviors Scale-II domains; the association was strongest for socialization followed by daily living skills and then communication. Mediation results remained significant for socialization only. CONCLUSIONS: Higher psychopathology burden was associated with worse adaptive functioning in early adolescence. This association was mediated by weaker dACC-dorsolateral prefrontal cortex functional connectivity underlying modulation of cognitive control in response to contextual contingencies. Our results contribute to the identification of transdiagnostic and developmentally relevant neurocognitive endophenotypes of psychopathology.

Isolation, purification and PEG-mediated transient expression of mesophyll protoplasts in Camellia oleifera.

BACKGROUND: Camellia oleifera (C. oleifera) is a woody edible oil crop of great economic importance. Because of the lack of modern biotechnology research, C. oleifera faces huge challenges in both breeding and basic research. The protoplast and transient transformation system plays an important role in biological breeding, plant regeneration and somatic cell fusion. The objective of this present study was to develop a highly efficient protocol for isolating and purifying mesophyll protoplasts and transient transformation of C. oleifera. Several critical factors for mesophyll protoplast isolation from C. oleifera, including starting material (leaf age), pretreatment, enzymatic treatment (type of enzyme, concentration and digestion time), osmotic pressure and purification were optimized. Then the factors affecting the transient transformation rate of mesophyll protoplasts such as PEG molecular weights, PEG4000 concentration, plasmid concentration and incubation time were explored. RESULTS: The in vitro grown seedlings of C. oleifera 'Huashuo' were treated in the dark for 24 h, then the 1st to 2nd true leaves were picked and vacuumed at - 0.07 MPa for 20 min. The maximum yield (3.5 × 107/g·FW) and viability (90.9%) of protoplast were reached when the 1st to 2nd true leaves were digested in the enzymatic solution containing1.5% (w/v) Cellulase R-10, 0.5% (w/v) Macerozyme R-10 and 0.25% (w/v) Snailase and 0.4 M mannitol for 10 h. Moreover, the protoplast isolation method was also applicable to the other two cultivars, the protoplast yield for 'TXP14' and 'DP47' was 1.1 × 107/g·FW and 2.6 × 107/g·FW, the protoplast viability for 'TXP14' and 'DP47' was 90.0% and 88.2%. The purification effect was the best when using W buffer as a cleaning agent by centrifugal precipitation. The maximum transfection efficiency (70.6%) was obtained with the incubation of the protoplasts with 15 µg plasmid and 40% PEG4000 for 20 min. CONCLUSION: In summary, a simple and efficient system for isolation and transient transformation of C. oleifera mesophyll protoplast is proposed, which is of great significance in various aspects of C. oleifera research, including the study of somatic cell fusion, genome editing, protein function, signal transduction, transcriptional regulation and multi-omics analyses.

Decreased Salinity Offsets the Stimulation of Elevated pCO2 on Photosynthesis and Synergistically Inhibits the Growth of Juvenile Sporophyte of Saccharina japonica (Laminariaceae, Phaeophyta).

The combined effect of elevated pCO2 (Partial Pressure of Carbon Dioxide) and decreased salinity, which is mainly caused by freshwater input, on the growth and physiological traits of algae has been poorly assessed. In order to investigate their individual and interactive effects on the development of commercially farmed algae, the juvenile sporophytes of Saccharina japonica were cultivated under different levels of salinity (30, 25 and 20 psu) and pCO2 (400 and 1000 µatm). Individually, decreased salinity significantly reduced the growth rate and pigments of S. japonica, indicating that the alga was low-salinity stressed. The maximum quantum yield, Fv/Fm, declined at low salinities independent of pCO2, suggesting that the hyposalinity showed the main effect. Unexpectedly, the higher pCO2 enhanced the maximum relative electron transport rate (rETRmax) but decreased the growth rate, pigments and soluble carbohydrates contents. This implies a decoupling between the photosynthesis and growth of this alga, which may be linked to an energetic reallocation among the different metabolic processes. Interactively and previously untested, the decreased salinity offset the improvement of rETRmax and aggravated the declines of growth rate and pigment content caused by the elevated pCO2. These behaviors could be associated with the additionally decreased pH that was induced by the low salinity. Our data, therefore, unveils that the decreased salinity may increase the risks of future CO2-induced ocean acidification on the production of S. japonica.

Symptom Burden of Children with Cancer and Parental Quality of Life: The Mediating Role of Parental Stress.

BACKGROUND: The aim of this study was to investigate the association between children's reported symptom burden and their parents' quality of life, and whether parents' perceived stress mediates this relationship. METHOD: this was a cross-sectional quantitative research study. Convenience sampling was used to recruit 80 pairs of parents and their children with cancer. Advanced statistical methods were used to analyse the mediating effects of parental stress between children's symptom burden and parents' quality of life. RESULTS: The results showed that parental stress was the mediator in the relationship between children's reported symptom burden and their parents' quality of life. CONCLUSIONS: Symptom burden was prevalent in Chinese children with cancer living in the community. Children's symptom burden is an important factor in predicting parental stress level, which simultaneously and directly lower parents' quality of life. The evidence in this study enlarges the knowledge base about the mediating effect of parental stress on the association between the symptom burden of children with cancer and their parents' quality of life. This evidence is crucial in paving the way for the development of interventions that improve the parental quality of life through stress-reduction programs.

Public attention, oil and gold markets during the COVID-19: Evidence from time-frequency analysis.

This paper uses time-frequency analysis, including wavelet analysis and time-frequency domain causality, to evaluate the relationship between public attention to the COVID-19 pandemic, crude oil, and gold markets in the G7 countries over time and frequency. Empirical findings show that WTI oil lead gold returns during the COVID-19 outbreak, and vice versa when Omicron spread. The relationship between public attention to the COVID-19 and WTI oil/gold markets appears to be heterogeneous for G7 countries. European public attention caused by the COVID-19 outbreak has a strong impact on gold returns at the 32-64 day frequency, while public attention generated by Omicron has a significant effect on WTI oil returns at 4-128 day frequency. The public in the US and Canada is more concerned about the global stock and WTI oil markets slump than the COVID-19 pandemic. The Italian public seems to be the most sensitive to the EU's economic support plan. The heterogeneity of the public attention-oil/gold nexus in the G7 implies that portfolio diversification across markets and investment horizons may be extremely beneficial.

PRKAR1A and SDCBP Serve as Potential Predictors of Heart Failure Following Acute Myocardial Infarction.

Background and Objectives: Early diagnosis of patients with acute myocardial infarction (AMI) who are at a high risk of heart failure (HF) progression remains controversial. This study aimed at identifying new predictive biomarkers of post-AMI HF and at revealing the pathogenesis of HF involving these marker genes. Methods and Results: A transcriptomic dataset of whole blood cells from AMI patients with HF progression (post-AMI HF, n = 16) and without progression (post-AMI non-HF, n = 16) was analyzed using the weighted gene co-expression network analysis (WGCNA). The results indicated that one module consisting of 720 hub genes was significantly correlated with post-AMI HF. The hub genes were validated in another transcriptomic dataset of peripheral blood mononuclear cells (post-AMI HF, n = 9; post-AMI non-HF, n = 8). PRKAR1A, SDCBP, SPRED2, and VAMP3 were upregulated in the two datasets. Based on a single-cell RNA sequencing dataset of leukocytes from heart tissues of normal and infarcted mice, PRKAR1A was further verified to be upregulated in monocytes/macrophages on day 2, while SDCBP was highly expressed in neutrophils on day 2 and in monocytes/macrophages on day 3 after AMI. Cell-cell communication analysis via the "CellChat" package showed that, based on the interaction of ligand-receptor (L-R) pairs, there were increased autocrine/paracrine cross-talk networks of monocytes/macrophages and neutrophils in the acute stage of MI. Functional enrichment analysis of the abovementioned L-R genes together with PRKAR1A and SDCBP performed through the Metascape platform suggested that PRKAR1A and SDCBP were mainly involved in inflammation, apoptosis, and angiogenesis. The receiver operating characteristic (ROC) curve analysis demonstrated that PRKAR1A and SDCBP, as well as their combination, had a promising prognostic value in the identification of AMI patients who were at a high risk of HF progression. Conclusion: This study identified that PRKAR1A and SDCBP may serve as novel biomarkers for the early diagnosis of post-AMI HF and also revealed their potentially regulatory mechanism during HF progression.

Endothelial Microparticle-Mediated Transfer of microRNA-19b Inhibits the Function and Distribution of Lymphatic Vessels in Atherosclerotic Mice.

In recent years, the function of the lymphatic system in atherosclerosis has attracted attention due to its role in immune cell trafficking, cholesterol removal from the periphery, and regulation of the inflammatory response. However, knowledge of the mechanisms regulating lymphangiogenesis and lymphatic function in the pathogenesis of atherosclerosis is limited. Endothelial microparticles carrying circulating microRNA (miRNA)s are known to mediate cell-cell communication, and our previous research showed that miRNA-19b in EMPs (EMPmiR-19b) was significantly increased in circulation and atherosclerotic vessels, and this increase in EMPmiR-19b promoted atherosclerosis. The present study investigated whether atherogenic EMPmiR-19b influences pathological changes of the lymphatic system in atherosclerosis. We first verified increased miR-19b levels and loss of lymphatic system function in atherosclerotic mice. Atherogenic western diet-fed ApoE-/- mice were injected with phosphate-buffered saline, EMPs carrying control miRNA (EMPcontrol), or EMPmiR-19b intravenously. The function and distribution of the lymphatic system was assessed via confocal microscopy, Evans blue staining, and pathological analysis. The results showed that lymphatic system dysfunction existed in the early stage of atherosclerosis, and the observed pathological changes persisted at the later stage, companied by an increased microRNA-19b level. In ApoE-/- mice systemically treated with EMPmiR-19b, the distribution, transport function, and permeability of the lymphatic system were significantly inhibited. In vitro experiments showed that miRNA-19b may damage the lymphatic system by inhibiting lymphatic endothelial cell migration and tube formation, and a possible mechanism is the inhibition of transforming growth factor beta receptor type II (TGF-ßRII) expression in lymphatic endothelial cells by miRNA-19b. Together, our findings demonstrate that atherogenic EMPmiR-19b may destroy lymphatic system function in atherosclerotic mice by downregulating TGF-ßRII expression.

Impact of High-Flux Hemodialysis on Chronic Inflammation, Antioxidant Capacity, Body Temperature, and Immune Function in Patients with Chronic Renal Failure.

In order to probe into the impact of high-flux dialysis and hemodiafiltration on patients with chronic rental failure, this paper selects in total 92 cases with chronic renal failure receiving hemodialysis from November 2018 to July 2021, allocating them into two groups based on the random table, each with 46 cases. The control group received hemodiafiltration, the observation group is given high-flux hemodialysis, and we compared serum inflammatory factor level and antioxidant factor level before and after treatment, as well as cellular immune factor level (CD3+, CD4+) and humoral immune factor level (IgE) before and after treatment in the two groups; the renal function, serum total calcium ion level, and serum phosphorus ion level in the two groups were compared before and after treatment, as well as the proportion of metabolic abnormalities in calcium and phosphorus ion levels during treatment; the trend of changes in axillary temperature during treatment in the two groups is analyzed. After treatment, serum inflammatory factor level (hs-CRP & TNF-α) is lower than that in the control group (P < 0.05), antioxidant factor level (MDA) is lower than that in the control group (P < 0.05), and SOD level is higher than that in the control group (P < 05). After treatment CD3+ and CD4+ levels in the observation group are higher than those in the control group (P < 0.05). For patients with chronic renal failure, high-flux hemodialysis is available to better reduce inflammatory response, improve antioxidant and immune capacity in the body, and help maintain calcium and phosphorus metabolic balance.

Parental Stress as the Mediator Between Symptom Burden and the Quality of Life of Chinese Children With Cancer.

BACKGROUND: Because of their cancer and treatment adverse effects, most pediatric oncology patients will experience 1 or more symptoms at one time that can seriously affect their quality of life. Because these children are attached to parents, their symptom burden directly influences the parental stress level and parental interpretations of their children's quality of life. OBJECTIVE: The aim of this study was to examine the association between child-reported symptom burden and the pediatric quality of life reported by children with cancer and their parents, and whether parental perceived stress mediates these relationships. METHODS: In a cross-sectional design, convenience sampling was used to recruit 80 parent-child dyads. Advanced statistical methods were adopted to analyze the mediating effects of parental stress between children's symptom burden and their quality of life. RESULTS: The results revealed that parental stress was the mediator in the relationship between child-reported symptom burden and children's quality of life reported by parents. The results also showed that parental stress was not a mediator in the relationship between child-reported symptom burden and their quality of life. This underscored the differences in interpretations of quality of life reported by children and their parents. CONCLUSION: Children's symptom burden is an important factor in predicting parental stress level and the quality of life reported by the children. Children's voice should be incorporated whenever possible. IMPLICATIONS FOR PRACTICE: The knowledge gained from this study will facilitate intervention development to enhance parents' abilities in stress management and symptom management for their children with the support of the nursing profession.

Generation of glucocorticoid-resistant SARS-CoV-2 T cells for adoptive cell therapy.

Adoptive cell therapy with virus-specific T cells has been used successfully to treat life-threatening viral infections, supporting application of this approach to coronavirus disease 2019 (COVID-19). We expand severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) T cells from the peripheral blood of COVID-19-recovered donors and non-exposed controls using different culture conditions. We observe that the choice of cytokines modulates the expansion, phenotype, and hierarchy of antigenic recognition by SARS-CoV-2 T cells. Culture with interleukin (IL)-2/4/7, but not under other cytokine-driven conditions, results in more than 1,000-fold expansion in SARS-CoV-2 T cells with a retained phenotype, function, and hierarchy of antigenic recognition compared with baseline (pre-expansion) samples. Expanded cytotoxic T lymphocytes (CTLs) are directed against structural SARS-CoV-2 proteins, including the receptor-binding domain of Spike. SARS-CoV-2 T cells cannot be expanded efficiently from the peripheral blood of non-exposed controls. Because corticosteroids are used for management of severe COVID-19, we propose an efficient strategy to inactivate the glucocorticoid receptor gene (NR3C1) in SARS-CoV-2 CTLs using CRISPR-Cas9 gene editing.

Targeting the αv integrin/TGF-ß axis improves natural killer cell function against glioblastoma stem cells.

Glioblastoma multiforme (GBM), the most aggressive brain cancer, recurs because glioblastoma stem cells (GSCs) are resistant to all standard therapies. We showed that GSCs, but not normal astrocytes, are sensitive to lysis by healthy allogeneic natural killer (NK) cells in vitro. Mass cytometry and single-cell RNA sequencing of primary tumor samples revealed that GBM tumor-infiltrating NK cells acquired an altered phenotype associated with impaired lytic function relative to matched peripheral blood NK cells from patients with GBM or healthy donors. We attributed this immune evasion tactic to direct cell-to-cell contact between GSCs and NK cells via αv integrin-mediated TGF-ß activation. Treatment of GSC-engrafted mice with allogeneic NK cells in combination with inhibitors of integrin or TGF-ß signaling or with TGFBR2 gene-edited allogeneic NK cells prevented GSC-induced NK cell dysfunction and tumor growth. These findings reveal an important mechanism of NK cell immune evasion by GSCs and suggest the αv integrin/TGF-ß axis as a potentially useful therapeutic target in GBM.

Metabolic Reprogramming of GMP Grade Cord Tissue Derived Mesenchymal Stem Cells Enhances Their Suppressive Potential in GVHD.

Acute graft-vs.-host (GVHD) disease remains a common complication of allogeneic stem cell transplantation with very poor outcomes once the disease becomes steroid refractory. Mesenchymal stem cells (MSCs) represent a promising therapeutic approach for the treatment of GVHD, but so far this strategy has had equivocal clinical efficacy. Therapies using MSCs require optimization taking advantage of the plasticity of these cells in response to different microenvironments. In this study, we aimed to optimize cord blood tissue derived MSCs (CBti MSCs) by priming them using a regimen of inflammatory cytokines. This approach led to their metabolic reprogramming with enhancement of their glycolytic capacity. Metabolically reprogrammed CBti MSCs displayed a boosted immunosuppressive potential, with superior immunomodulatory and homing properties, even after cryopreservation and thawing. Mechanistically, primed CBti MSCs significantly interfered with glycolytic switching and mTOR signaling in T cells, suppressing T cell proliferation and ensuing polarizing toward T regulatory cells. Based on these data, we generated a Good Manufacturing Process (GMP) Laboratory protocol for the production and cryopreservation of primed CBti MSCs for clinical use. Following thawing, these cryopreserved GMP-compliant primed CBti MSCs significantly improved outcomes in a xenogenic mouse model of GVHD. Our data support the concept that metabolic profiling of MSCs can be used as a surrogate for their suppressive potential in conjunction with conventional functional methods to support their therapeutic use in GVHD or other autoimmune disorders.