Metabolomic and Transcriptomic Analyses Reveal the Molecular Mechanism Underlying the Massive Accumulation of Secondary Metabolites in Fenugreek (Trigonella foenum-graecum L.) Seeds.

Fenugreek (Trigonella foenum-graecum L.) is a traditional medicinal plant for treating human diseases that is widely cultivated in many countries. However, the component and related metabolic pathways are still unclear. To understand the changes in expression of the component and related genes during seed development, this study employed metabolomic and transcriptomic analyses and integrative analysis to explore the metabolites and pathways involved in the growth of fenugreek. The antifungal activity of the fenugreek seeds was also analyzed. A total of 9499 metabolites were identified in the positive ion mode, and 8043 metabolites were identified in the negative ion mode. Among them, the main components were fatty acyls, prenol lipids, steroids, steroid derivatives, flavonoids, and isoflavonoids. Among these enriched pathways, the top 20 pathways were "flavone and flavonol biosynthesis", "isoflavonoid biosynthesis", and "flavonoid biosynthesis". 3,7-Di-O-methylquercetin, flavonoids, pseudobaptigenin, isoflavonoids, methylecgonine, alkaloids, and derivatives were the most significantly upregulated metabolites. There were 38,137 differentially expressed genes (DEGs) identified via transcriptomic analysis. According to the KEGG pathway enrichment analysis, 147 DEGs were significantly enriched in "flavonoid biosynthesis". Ten DEGs of the six key enzymes were found to be involved in three pathways related to flavonoid and alkaloid synthesis in fenugreek. The antifungal activity test revealed the inhibitory effect of the ethanol extract of fenugreek seeds on Alternaria tenuissima (Kunze)Wiltshire and Magnaporthe oryzae. These findings further prove that the use of botanical pesticides in fenugreek fruit has research value.

Parastomal Hernia Following Ileal Conduit: Incidence, Risk Factors, and Health-Related Quality of Life.

PURPOSE: The purpose of this study was to measure the incidence of parastomal hernia (PH) after radical cystectomy and ileal conduit. Secondary aims were the identification of risk factors for PH and to compare the health-related quality of life (QOL) between patients with and without PH. DESIGN: Retrospective review of medical records combined with cross-sectional administration of the QOL instrument and telephone follow-up. SUBJECTS AND SETTING: The study sample comprised 219 patients who underwent radical cystectomy and ileal conduit for urothelial cancer between February 2014 and December 2018. The study setting was Peking University First Hospital (Beijing, China). METHODS: Demographic and pertinent clinical data, including development of PH, were gathered via the retrospective review of medical records. Participants were also asked to complete the traditional Chinese language version of the City of Hope Quality of Life-Ostomy Questionnaire (C-COH). Multiple linear regression analysis was used to identify the effect of PH on C-COH scores. Logistic regression analysis was used to identify risk factors for PH development. RESULTS: At a median follow-up of 34 months (IQR = 21-48), 43 of 219 (19.63%) patients had developed a PH. A body mass index (BMI) indicating overweight (OR = 3.548; 95% CI, 1.562-8.061; P = .002), a prior history of hernia (OR = 5.147; 95% CI, 1.195-22.159; P = .028), and chronic high abdominal pressure postdischarge (CHAP-pd) (OR = 3.197; 95% CI, 1.445-7.075; P = .004) were predictors of PH after operation. There was no significant difference between C-COH scores of patients with or without PH. No significant differences were found when participants with PH were compared to those without PH on 4 factors of the C-COH: physical scores (ß= .347, P = .110), psychological scores (ß= .316, P = .070), spiritual scores (ß=-.125, P = .714), and social scores (ß= .054, P = .833). CONCLUSION: Parastomal hernia is prevalent in patients undergoing radical cystectomy and ileal conduit urinary diversion. Overweight, hernia history, and CHAP-pd were predictors of PH development. No significant differences in QOL were found when patients with PH were compared to those without PH.

Variation of gene expression of fatty acid acyl CoA reductase associated with wax secretion of a scale insect, Ericerus pela, and identification of its regulation factors through the accessible chromatin analyses and yeast one-hybrid.

The Chinese white wax scale insect (CWWSI), Ericerus pela, can secret an amount of wax equivalent to their body weight. Previous studies demonstrated the fatty acyl-CoA reductase (far3) plays a pivotal role in wax secretion of CWWSI. The high expression of far3 is crucial for the massive wax secretion. However, the transcription regulation of far3 was not clear. To identify regulatory factors that control the expression of far3, the assay for transposase-accessible chromatin (ATAC) and yeast one-hybrid (Y1H) were carried out in this study. The ATAC sequencing of the CWWSI at the early wax-secretion stage ATAC-seq resulted in 22.75 GB raw data, generated 75,827,225 clean reads and revealed 142,771 peaks. There was one significant peak in the 3 kb upstream regulation regions. The peak sequence is located between -1000 and -670 bp upstream of the far3 transcription start site, spanning a length of 331 bp. This peak sequence served as bait for creating the pAbAi-peak recombinant vector, used in Y1H screenings to identify proteins interacting with far3 gene. The results indicate a successful CWWSI cDNA library construction with a capacity of 1.2 × 107 colony forming unit, a 95.8% recombination rate, and insert sizes between 1,000 and 2,000 bp. Self-activation tests established that 100 ng/mL of AbA effectively inhibited bait vector self-activation. Finally, a total of 88 positive clones were selected. After sequencing and removal of duplication, 63 unique clones were obtained from these screened colonies. By aligning the clone sequences with full-length transcriptome and genome of CWWSI, the full-length coding sequences of these clones were obtained. BlastX analysis identified a transcription factor, nuclear transcription factor Y beta, and two co-activators, cAMP-response-element-binding-protein-binding protein and WW domain binding protein 2. Reverse transcription quantitative polymerase chain reaction analysis confirmed that their expression patterns were consistent with the developmental stages preceding wax secretion and matched the wax secretion characteristics during ovulation periods. These results are beneficial for further research into the regulatory mechanisms of wax secretion of CWWSI.

Molecular characterization of a novel mycovirus from binucleate Rhizoctonia AG-A strain A46.

The complete genome sequence of a positive-sense single-stranded RNA (+ ssRNA) virus, Rhizoctonia beny-like virus 1 (RBLV1), isolated from binucleate Rhizoctonia AG-A strain A46, was determined. The RBLV1 genome is 10,280 nt in length and contains a short stretch of adenines at the 3' terminus. It contains a single open reading frame (ORF) encoding a 376.30-kDa protein with viral helicase and RNA-dependent RNA polymerase (RdRp) motifs. The encoded protein exhibited the highest sequence similarity to Rhizoctonia cerealis beny-like virus 0928-1 (RcBeLV 0928-1, 45.25%), with a sequence coverage of 63%. Phylogenetic analysis based on ORF protein sequences revealed that RBLV1 is a novel unclassified mycovirus.

Amorphous MoS2 Decorated Ni3 S2 with a Core-shell Structure of Urchin-Like on Nickel-Foam Efficient Hydrogen Evolution in Acidic and Alkaline Media.

The large-scale commercialization of the hydrogen evolution reaction (HER) necessitates the development of cost-effective and highly efficient electrocatalysts. Although transition metal sulfides, such as MoS2 and Ni3 S2 , hold great potential in the field of HER, their catalytic performance has been unsatisfactory due to incomplete exposure of active sites and poor electrical conductivity. In this work, via a simple hydrothermal strategy, amorphous MoS2 nanoshells in the form of urchin-like MoS2 -Ni3 S2 core-shell heterogeneous structure is realized and in situ loaded on nickel foam (A-MoS2 -Ni3 S2 -NF). In particular, XPS analysis results show that the coupling of amorphous MoS2 and Ni3 S2 makes the electrode surface exhibit electron-abundant property, which will have a positive impact on HER catalytic activity. In addition, the fully exposed active site of amorphous MoS2 is another crucial factor contributing to its high catalytic performance of A-MoS2 -Ni3 S2 -NF electrode. In particular, at a current density of 10 mA cm⁻2 , the overpotential of electrode is 95 mV (1.0 m KOH) and 145 mV (0.5 m H2 SO4 ). This work highlights the importance of amorphous MoS2 and MoS2 -Ni3 S2 of sea-urchin core-shell structure in optimizing HER performance, which provides an important reference for HER research.

Identification and nucleotide sequencing of a novel partitivirus derived from Rhizoctonia solani AG-4 HG III isolate A14.

Rhizoctonia solani is a widely disseminated phytopathogen that is found in the soil and is capable of harming many important species of crops. Here, analysis of the R. solani AG-4 HG III strain A14 led to the identification of a novel mycovirus assigned the tentative name "Rhizoctonia solani partitivirus A14" (RsPV-A14), which was subjected to sequencing and associated analyses. This approach revealed that RsPV-A14 harbored two dsRNA segments, 2022 bp (dsRNA1) and 1905 bp (dsRNA2) in length. dsRNA1 was found to contain a single open reading frame (ORF1) that codes for a 622-amino-acid protein with conserved RNA-dependent RNA polymerase (RdRp) motifs, and dsRNA2 was found to contain an ORF (ORF2) that is predicted to code for a 558-amino-acid capsid protein (CP). BLASTp analysis using the putative RdRp of RsPV-A14 showed sequence similarity to partitiviruses, including Rosellinia necatrix partitivirus 7 (50.53% identity), an unclassified partitivirus. Phylogenetic analysis based on RdRp protein sequences suggested that RsPV-A14 is a novel member of the family Partitiviridae.

Characterization, Recombinant Production, and Bioactivity of a Novel Immunomodulatory Protein from Hypsizygus marmoreus.

A novel fungal immunomodulatory protein (FIP), identified as FIP-hma, was discovered in the genome of an edible mushroom Hypsizygus marmoreus. Bioinformatics analysis suggested FIP-hma contained the cerato-platanin (CP) conserved domain and was categorized into Cerato-type FIP. In phylogenetic analysis, FIP-hma was clustered into a new branch of the FIP family, displaying large system divergence from most of the other FIPs. The higher gene expression of FIP-hma was observed during the vegetative growth stages than that during the reproductive growth stages. In addition, the cDNA sequence of FIP-hma was cloned and successfully expressed in Escherichia coli (E. coli) BL21(DE3). The recombinant protein of FIP-hma (rFIP-hma) was neatly purified and isolated by Ni-NTA and SUMO-Protease. The iNOS, IL-6, IL-1ß, and TNF-α levels of RAW 264.7 macrophages were upregulated by rFIP-hma, indicating its activation of an immune response by regulating central cytokines. No cytotoxic effects were observed in an MTT test. The findings of this work discovered a novel immunoregulatory protein from H. marmoreus, provided a systematic bioinformatic profile, suggested an effective approach for its heterologous recombinant production, and reported its potent immunoregulatory activity in macrophages. This study sheds light on the physiological function research of FIPs and their further industrial utilization.

[Anti-fatigue effect of Lubian on kidney Yin deficiency and kidney Yang deficiency mice and mechanism based on PI3K-Akt pathway].

This study aimed to investigate the anti-fatigue effect and mechanism of Lubian(Cervi Penis et Testis) on kidney Yin deficiency and kidney Yang deficiency mice. After one week of adaptive feeding, 88 healthy male Kunming mice were randomly divided into a blank group, a kidney Yin deficiency model group, a kidney Yin deficiency-Panacis Quinquefolii Radix(PQR) group, kidney Yin deficiency-Lubian treatment groups, a kidney Yang deficiency model group, a kidney Yang deficiency-Ginseng Radix et Rhizoma(GR) group, and kidney Yang deficiency-Lubian treatment groups, with eight mice in each group. The kidney Yin deficiency model and kidney Yang deficiency model were prepared by daily regular oral administration of dexamethasone acetate and hydrocortisone, respectively, and meanwhile, corresponding drugs were provided. The mice in the blank group received blank reagent. The treatment lasted 14 days. The exhaustive swimming time was measured 30 min after drug administration on the 14th day. On the 15th day, blood was collected from eyeballs and the serum was separated to determine the content of lactic acid(LD), blood urea nitrogen(BUN), lactate dehydrogenase(LDH), cyclic adenosine monophosphate(cAMP), and cyclic guanosine monophosphate(cGMP). The liver was dissected to determine the content of liver glycogen and the protein expression of phosphoinositide 3-kinase(PI3K) and protein kinase B(Akt). Compared with the kidney Yang deficiency model group, the kidney Yang deficiency-Lubian treatment groups showed increased body weight(P<0.05), relieved symptoms of Yang deficiency, decreased cGMP content(P<0.01), increased cAMP/cGMP(P<0.01), prolonged exhausted swimming time(P<0.01), reduced LD(P<0.01), elevated BUN content(P<0.01), increased liver glycogen content(P<0.01), and increased protein expression of PI3K and Akt in the liver(P<0.05). Compared with the kidney Yin deficiency model group, the kidney Yin deficiency-Lubian treatment groups showed increased body weight(P<0.01), relieved symptoms of Yin deficiency, increased content of cGMP(P<0.01), decreased cAMP/cGMP(P<0.01), prolonged exhausted swimming time(P<0.01), decreased LD(P<0.01), decreased BUN content(P<0.01), increased liver glycogen content(P<0.01), and increased protein expression of PI3K(P<0.05) and Akt in the liver(P<0.05). To sum up, Lubian can regulate Yin deficiency and Yang deficiency and increase glycogen synthesis by affecting the PI3K-Akt pathway, thereby exerting an anti-fatigue role.

The Complete Mitochondrial Genome of the Chinese White Wax Scale Insect, Ericerus pela Chavannes (Hemiptera: Coccidae), with Novel Gene Arrangement and Truncated tRNA Genes.

The Chinese white wax scale insect, Ericerus pela Chavannes (Hemiptera: Coccidae), is one of the scale insects with great economic value and has been dispersed and reared in China for over one thousand years. Its mitochondrial genome provides essential information for the molecular identification and genetic study of this species. We assembled the complete mitochondrial genome of E. pela based on PacBio sequencing and analyzed its genomic features. The genome was 17,766 bp in length with 13 protein-coding genes, 22 tRNAs, and two rRNA genes. The analysis results showed E. pela had significant gene rearrangements involving tRNAs compared with other Coccoidea species. Furthermore, E. pela's nine tRNAs were identified to have obvious truncated structures. The phylogenetic tree compiled of the species showed a long branch of the Coccoidea lineage, which indicated the high evolutionary rate in this group. Our study revealed the mitochondrial characteristics of E. pela and enriched the mitochondrial genetic information on Coccoidea species. It also determined the occurrence of gene rearrangement for the species in this superfamily.

High-fidelity and clean nanotransfer lithography using structure-embedded and electrostatic-adhesive carriers.

Metallic nanostructures are becoming increasingly important for both fundamental research and practical devices. Many emerging applications employing metallic nanostructures often involve unconventional substrates that are flexible or nonplanar, making direct lithographic fabrication very difficult. An alternative approach is to transfer prefabricated structures from a conventional substrate; however, it is still challenging to maintain high fidelity and a high yield in the transfer process. In this paper, we propose a high-fidelity, clean nanotransfer lithography method that addresses the above challenges by employing a polyvinyl acetate (PVA) film as the transferring carrier and promoting electrostatic adhesion through triboelectric charging. The PVA film embeds the transferred metallic nanostructures and maintains their spacing with a remarkably low variation of <1%. When separating the PVA film from the donor substrate, electrostatic charges are generated due to triboelectric charging and facilitate adhesion to the receiver substrate, resulting in a high large-area transfer yield of up to 99.93%. We successfully transferred the metallic structures of a variety of materials (Au, Cu, Pd, etc.) with different geometries with a <50-nm spacing, high aspect ratio (>2), and complex 3D structures. Moreover, the thin and flexible carrier film enables transfer on highly curved surfaces, such as a single-mode optical fiber with a curvature radius of 62.5 µm. With this strategy, we demonstrate the transfer of metallic nanostructures for a compact spectrometer with Cu nanogratings transferred on a convex lens and for surface-enhanced Raman spectroscopy (SERS) characterization on graphene with reliable responsiveness.

The mediating role of resilience in the relationship between social support and quality of life among patients after radical cystectomy: A structural equation model analysis.

AIM: This study aimed to examine the relationship between social support and quality of life in urostomy patients and identify the mediating role of resilience in that relationship. DESIGN: A cross-sectional design. METHODS: Participants included 232 patients who were recruited from a tertiary hospital in Beijing during March 2020 and August 2020. They completed questionnaires about perceived social support, resilience and ostomy-related quality of life. Structural equation modelling was performed to analyse the data. RESULTS: The mean age of patients was 65.79 (SD = 8.67) years, and the mean length of time after surgery was 42.14 (SD = 15.76) months. Urostomy patients' quality of life, social support and resilience were all above moderate. Social support had a positive direct effect on the quality of life and a positive indirect effect on the quality of life through the mediating role of resilience.

Hepatitis B or C viral infection and the risk of cervical cancer.

BACKGROUND: The present study aimed to evaluate the effects of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection on the risk of cervical cancer. METHODS: We conducted a case-control study including 838 cervical cancer cases and 838 benign disease controls matched for age, ethnicity, and place of birth. Venous blood was tested for HBV and HCV serological markers. Multiple odds ratios (OR) and corresponding 95% confidence intervals (CI) for cervical cancer were estimated using logistic regression. HBV antigens were examined using immunohistochemical staining. RESULTS: Anti-HCV was positive in 10 cases (1.2%) and 0 controls (0%). Cases had higher percentage of chronic HBV infection (HBsAg-positive/anti-HBc-positive) and prior HBV infection (HBsAg-negative/anti-HBc-positive) than controls (6.3% vs 4.4%; 11.6% vs 7.3%). Both chronic HBV infection (OR 1.6; 95% CI 1.0-2.4) and prior HBV infection (OR 1.7; 95% CI 1.2-2.4) were associated with cervical cancer in univariate logistic regression analyses. In subgroup analysis among HPV-positive patients, the association between chronic HBV infection and cervical cancer disappeared (OR 1.2; 95% CI 0.4-3.4); while in subgroup among patients younger than 50 years, the association remained significant with adjustment for HPV infection and parity (adjusted OR 2.1; 95% CI 1.0-4.4). HBsAg and HBcAg were detected in 8% and 12% of cervical cancer cases who had seropositive HBsAg, respectively. Compared with the benign controls, individuals with both HBsAg and HPV positive had an increased risk of cervical cancer (adjusted OR 67.1; 95% CI 23.4-192.7). CONCLUSIONS: HBV infection was associated with cervical cancer in patients with age younger than 50 years. Further prospective studies are needed to confirm this relationship.

Status of core competencies of wound, ostomy and continence nurses and their influence on career success: a cross-sectional study.

OBJECTIVES: The wound, ostomy and continence nursing practice has its own scope and standards, and each standard requires relevant competency. However, the core competencies of wound, ostomy and continence nurses that contribute to the career success are poorly known. To identify associations between career success and core competencies of wound, ostomy and continence nurses in China. DESIGN: A cross-sectional survey with a convenience sample. SETTING: Participants were recruited from 108 hospitals in 28 provinces. PARTICIPANTS: A total of 123 wound, ostomy and continence nurses were surveyed. MEASURES: Career success, core competencies and demographic characteristics of wound, ostomy and continence nurses, were measured in this study. METHODS: A survey was distributed to 123 wound, ostomy and continence nurses were recruited from 108 hospitals in 28 provinces. Multivariate logistic regression was undertaken to explore associations between career success outcomes and core competency scores of wound ostomy and continence nurses and their demographic characteristics. RESULTS: The career success and core competency of wound, ostomy and continence nurses were both above average. Nurses who had higher total scores of core competency were more likely to have higher career success, including total score (OR=4.90), career satisfaction (OR=5.58) and perceived internal (OR=4.55)/external (OR=3.42) organisation competitiveness. Higher competency in interpersonal communication (OR=7.70) and more time for wound care per month (OR=8.80) predicted higher career satisfaction. Additionally, nurses with higher professional development were more likely to score higher in perceived internal organisation competitiveness of career success (OR=4.36) and the overall career success (OR=5.96). CONCLUSIONS: The career success and core competency of the wound, ostomy and continence nurses in China were at an above average level. The associations between career success and core competency of the wound, ostomy and continence nurses were positive, suggesting that competency enhancement could improve nurses' career success.

Polyimide Films Impregnated with Epoxy Resin Demonstrating Superior Self-Healing Properties for Thermally Stable Energy Storage Capacitors.

Metallized polymer films (MPFs) with superior self-healing properties are extremely attractive for application in energy storage capacitors. Self-healing behaviors allow MPFs to keep insulating between the local electrical breakdown region and the electrode, thereby reserving long-term operational viability of the capacitors. Polyimide (PI) is a type of well-developed polymer material with excellent mechanical and thermal stabilities, but it is deficient in intrinsic self-healing capabilities. This work reports a facile surface engineering strategy to endow metalized PI films with self-healing capabilities. By simple immersion of bare PI films in the solution of epoxy resin (ER) accompanied by curing of ER, PI films impregnated with ER (P-E films) not only show enhanced dielectric characteristics but also obtain excellent self-healing abilities upon multiple cycles of electrical breakdowns, even at a high temperature. For example, in comparison to bare PI films, PI films impregnated in ER solution with a solid content of 1 wt % (P-1%E) display improved initial Weibull breakdown strength (αb1 of 353.0 versus 310.9 kV/mm), maximum discharging energy density (Ud of 2.1836 versus 0.8254 J/cm3), and charging/discharging efficiency (η of 95.72 versus 55.19%) at 150 °C. After 5 breakdown cycles, P-1%E films could maintain a much higher breakdown strength (αb5 of 338.1 versus 21.3 kV/mm). When subjected to a constant electrical strength of 350 kV/mm at 150 °C, P-1%E films show merely <6% decline in both Ud and η values after 5 breakdown cycles. On the contrary, bare PI films would undergo dramatic performance decay after 1 or 2 breakdowns under similar conditions. In view of their outstanding self-healing properties at a high temperature, P-E films can serve as a promising candidate to fabricate thermally stable MPF capacitors for long-term operation.

Antioxidative and Energy Metabolism-Improving Effects of Maca Polysaccharide on Cyclophosphamide-Induced Hepatotoxicity Mice via Metabolomic Analysis and Keap1-Nrf2 Pathway.

Lepidium meyenii Walp. (Maca), as a natural food supplement, has strong antioxidant and energy metabolism-improving characteristics, and Maca polysaccharide (MP) is its effective component. MP has been shown to mitigate liver damage in previous research, and Cyclophosphamide (CYP)-induced hepatotoxicity is also a major concern in clinical practice. We investigated the possible cytoprotective effect of MP on CYP-induced liver injury, and explored its underlying mechanism by analyzing the resulting liver metabolic profiles. MP significantly inhibited increases in serum transaminase, improved pathological changes, reduced oxidative stress, and increased the levels of energy metabolism-related enzymes. Metabolomic analysis showed that MP corrected lipid metabolic problems and regulated the pentose phosphate pathway and acid metabolism, thereby protecting against apoptosis of hepatocytes. The Pearson correlation analysis indicated that antioxidant enzymes and energy metabolism-related enzymes are closely correlated with these differential metabolites. In addition, the upstream Keap1-Nrf2 antioxidant signal transduction pathway was explored to validate the possible mechanism of the cytoprotective effect of MP. In conclusion, MP plays a protective role in CYP-induced hepatotoxicity through these potential metabolic means, where it ameliorates oxidative stress, improves energy metabolism, and restores mitochondrial respiration by regulating the Keap1-Nrf2 signaling pathway, thereby preventing liver damage.

Effect of Noni on Memory Impairment Induced by Hydrocortisone in Mice.

Background: Oxidative stress and memory impairment have been implicated as common functional brain diseases. Nuclear factor E2-related factor 2 (Nrf2) is highly induced in oxidative stress, indicating that Nrf2 is an emerging target of memory therapy. This study aimed to investigate the effect of noni on brain memory impairment induced by hydrocortisone and its protective mechanism in mice. Methods: Male Kunming mice (n = 8/group) were given hydrocortisone by gastric gavage for 14 consecutive days to establish the memory impairment model, except for those in the control group. On the same day, the corresponding drugs were given by gastric gavage. The changes in ethology were examined. The brains were extracted and subjected to western blot analysis and biochemical analyses to assess the activities of antioxidative stress. Results: The middle- and high-dose noni groups exhibited ameliorated ethology, and the high-dose noni group exhibited increased cerebral protein expression of Nrf2, Kelch-like ECH-associated protein 1 (KEAP1), and haem oxygenase-1 (HO-1) compared to the model group. The arrangement of CA3 vertebral cells in the hippocampus of mice was slightly compact, and hyperchromasia and pyknosis were alleviated. Furthermore, biochemical analyses showed that the activities of enzymes related to oxidative stress in the high-dose noni group were increased. Conclusions: Noni might be a powerful antioxidant that can protect nerve cells and may possess potential benefits for the treatment of memory impairment.

A Retrospective Study of Diaphragmatic Breathing Training Combined with Discharge Care Bundles in Patients with Chronic Obstructive Pulmonary Disease.

Objective: Both physical exercise and discharge care bundles can improve patient outcomes and reduce hospitalization rates among subjects with chronic obstructive pulmonary disease (COPD). The retrospective analysis aims to determine the advantages of care bundles combined with diaphragmatic breathing training (DBT) in COPD patients after discharge. Methods: Of the 110 COPD patients, 55 patients received DBT alone (DBT group) and 55 participants received the combined intervention (care bundle + DBT group). Three months after discharge, we assessed the outcomes of patients using Bristol COPD Knowledge Questionnaire (BCKQ), Hospital Anxiety and Depression Scale (HADS), COPD Assessment Test (CAT), and St. George's Respiratory Questionnaire (SGRQ). Meanwhile, COPD-related hospital readmissions were also recorded. Results: The BCKQ score for assessing the disease knowledge level was increased in patients at 3 months after the combined interventions as compared to the baseline values, which was higher in the care bundle + DBT group than the DBT group at 3 months. Moreover, improvements in negative emotion and clinical symptoms from baseline to 3-month follow-up were seen in both the two groups. Besides, the care bundle + DBT group showed the mitigation of depression and anxiety and the alleviation of clinical symptoms in comparison with the DBT group at 3 months. Participants who received combined interventions had lower SGRQ scores than those who received DBT alone. The time to first COPD-related readmission was shorter for patients in the care bundle + DBT group compared with the DBT group. Conclusions: DBT combined with discharge care bundles for COPD patients resulted in improvements in disease-specific knowledge, negative emotions, and clinical symptoms with better HRQOL and lower readmission rate.

Genetically modified CD7-targeting allogeneic CAR-T cell therapy with enhanced efficacy for relapsed/refractory CD7-positive hematological malignancies: a phase I clinical study.

Chimeric antigen receptor (CAR)-T cell therapy against T cell malignancies faces major challenges including fratricide between CAR-T cells and product contamination from the blasts. Allogeneic CAR-T cells, generated from healthy donor T cells, can provide ready-to-use, blast-free therapeutic products, but their application could be complicated by graft-versus-host disease (GvHD) and host rejection. Here we developed healthy donor-derived, CD7-targeting CAR-T cells (RD13-01) with genetic modifications to resist fratricide, GvHD and allogeneic rejection, as well as to potentiate antitumor function. A phase I clinical trial (NCT04538599) was conducted with twelve patients recruited (eleven with T cell leukemia/lymphoma, and one with CD7-expressing acute myeloid leukemia). All patients achieved pre-set end points and eleven proceeded to efficacy evaluation. No dose-limiting toxicity, GvHD, immune effector cell-associated neurotoxicity or severe cytokine release syndrome (grade ≥ 3) were observed. 28 days post infusion, 81.8% of patients (9/11) showed objective responses and the complete response rate was 63.6% (7/11, including the patient with AML). 3 of the responding patients were bridged to allogeneic hematopoietic stem cell transplantation. With a median follow-up of 10.5 months, 4 patients remained in complete remission. Cytomegalovirus (CMV) and/or Epstein-Barr virus (EBV) reactivation was observed in several patients, and one died from EBV-associated diffuse large B-cell lymphoma (DLBCL). Expansion of CD7-negative normal T cells was detected post infusion. In summary, we present the first report of a Phase I clinical trial using healthy donor-derived CD7-targeting allogeneic CAR-T cells to treat CD7+ hematological malignancies. Our results demonstrated the encouraging safety and efficacy profiles of the RD13-01 allogeneic CAR-T cells for CD7+ tumors.

Immunomodulatory Effects of Lepidium meyenii Walp. Polysaccharides on an Immunosuppression Model Induced by Cyclophosphamide.

Background: Lepidium meyenii Walp. (Maca) has emerged as a functional plant food and traditional herb owing to its biological activities; Maca polysaccharides as an important active component of Maca have good immunomodulatory effect; however, studies on the immunomodulatory effect of Maca polysaccharides are mainly focused on macrophages; little attention has been devoted to the mechanisms and other immune cells. This study is aimed at investigating the immunomodulatory effects and mechanisms of Maca polysaccharides. Methods: Sixty mice were divided into five groups, and the mice were injected with cyclophosphamide to establish an immunosuppression model except for those in the common group. The body weights were measured, as well as immune-related indices, such as organ indices, haematological parameters, lymphocyte cycle, and proliferation, cytokine, and protein expression levels. Results: The weight loss and immune organ index decline caused by cyclophosphamide could be reversed by MP. Furthermore, MP increased WBC and HGB counts and reduced the ratio of G0/G1 phase obviously, increased the proportion of S phase and G2/M phase in peripheral blood lymphocytes, increased the counts of CD4+ T cells and the ratio of CD4+/CD8+, and reduced the inhibition rate of splenic lymphocytes. MP affected the production of cytokines by increasing IFN-γ, TNF-α, and IL-2 levels and by decreasing IL-4 levels. MP increased the mRNA expression of T-bet and the protein expression of Bcl-2 in the spleen and decreased the protein expression of caspase-3 and Bax. Conclusions: Maca polysaccharides might be the basic material for Maca's immunomodulatory effect. The mechanism was perhaps related to inhibiting lymphocyte apoptosis and promoting the balance of Th1/Th2 cell subsets.

Ferroelectricity and Piezoelectricity in 2D Van der Waals CuInP2S6 Ferroelectric Tunnel Junctions.

CuInP2S6 (CIPS) is a novel two-dimensional (2D) van der Waals (vdW) ferroelectric layered material with a Curie temperature of TC~315 K, making it promising for great potential applications in electronic and photoelectric devices. Herein, the ferroelectric and electric properties of CIPS at different thicknesses are carefully evaluated by scanning probe microscopy techniques. Some defects in some local regions due to Cu deficiency lead to a CuInP2S6-In4/3P2S6 (CIPS-IPS) paraelectric phase coexisting with the CIPS ferroelectric phase. An electrochemical strain microscopy (ESM) study reveals that the relaxation times corresponding to the Cu ions and the IPS ionospheres are not the same, with a significant difference in their response to DC voltage, related to the rectification effect of the ferroelectric tunnel junction (FTJ). The electric properties of the FTJ indicate Cu+ ion migration and propose that the current flow and device performance are dynamically controlled by an interfacial Schottky barrier. The addition of the ferroelectricity of CIPS opens up applications in memories and sensors, actuators, and even spin-orbit devices based on 2D vdW heterostructures.