Rice DWARF AND LOW-TILLERING and the homeodomain protein OSH15 interact to regulate internode elongation via orchestrating brassinosteroid signaling and metabolism.

Brassinosteroid (BR) phytohormones play crucial roles in regulating internode elongation in rice (Oryza sativa). However, the underlying mechanism remains largely unclear. The dwarf and low-tillering (dlt) mutant is a mild BR-signaling-defective mutant. Here, we identify two dlt enhancers that show more severe shortening of the lower internodes compared to the uppermost internode (IN1). Both mutants carry alleles of ORYZA SATIVA HOMEOBOX 15 (OSH15), the founding gene for dwarf6-type mutants, which have shortened lower internodes but not IN1. Consistent with the mutant phenotype, OSH15 expression is much stronger in lower internodes, particularly in IN2, than IN1. The osh15 single mutants have impaired BR sensitivity accompanied by enhanced BR synthesis in seedlings. DLT physically interacts with OSH15 to co-regulate many genes in seedlings and internodes. OSH15 targets and promotes the expression of the BR receptor gene BR INSENSITIVE1 (OsBRI1), and DLT facilitates this regulation in a dosage-dependent manner. In osh15, dlt, and osh15 dlt, BR levels are higher in seedlings and panicles, but unexpectedly lower in internodes compared with the wild-type. Taken together, our results suggest that DLT interacts with OSH15, which functions in the lower internodes, to modulate rice internode elongation via orchestrating BR signaling and metabolism.

Immunoadjuvant-Modified Rhodobacter sphaeroides Potentiate Cancer Photothermal Immunotherapy.

Photothermal immunotherapy has become a promising strategy for tumor treatment. However, the intrinsic drawbacks like light instability, poor immunoadjuvant effect, and poor accumulation of conventional inorganic or organic photothermal agents limit their further applications. Based on the superior carrying capacity and active tumor targeting property of living bacteria, an immunoadjuvant-intensified and engineered tumor-targeting bacterium was constructed to achieve effective photothermal immunotherapy. Specifically, immunoadjuvant imiquimod (R837)-loaded thermosensitive liposomes (R837@TSL) were covalently decorated onto Rhodobacter sphaeroides (R.S) to obtain nanoimmunoadjuvant-armed bacteria (R.S-R837@TSL). The intrinsic photothermal property of R.S combined R837@TSL to achieve in situ near-infrared (NIR) laser-controlled release of R837. Meanwhile, tumor immunogenic cell death (ICD) caused by photothermal effect of R.S-R837@TSL, synergizes with released immunoadjuvants to promote maturation of dendritic cells (DCs), which enhance cytotoxic T lymphocytes (CTLs) infiltration for further tumor eradication. The photosynthetic bacteria armed with immunoadjuvant-loaded liposomes provide a strategy for immunoadjuvant-enhanced cancer photothermal immunotherapy.

ARGONAUTE2 Enhances Grain Length and Salt Tolerance by Activating BIG GRAIN3 to Modulate Cytokinin Distribution in Rice.

Maintaining stable, high yields under fluctuating environmental conditions is a long-standing goal of crop improvement but is challenging due to internal trade-off mechanisms, which are poorly understood. Here, we identify ARGONAUTE2 (AGO2) as a candidate target for achieving this goal in rice (Oryza sativa). Overexpressing AGO2 led to a simultaneous increase in salt tolerance and grain length. These benefits were achieved via the activation of BIG GRAIN3 (BG3), encoding a purine permease potentially involved in cytokinin transport. AGO2 can become enriched on the BG3 locus and alter its histone methylation level, thus promoting BG3 expression. Cytokinin levels decreased in shoots but increased in roots of AGO2-overexpressing plants. While bg3 knockout mutants were hypersensitive to salt stress, plants overexpressing BG3 showed strong salt tolerance and large grains. The knockout of BG3 significantly reduced grain length and salt tolerance in AGO2-overexpressing plants. Both genes were transcriptionally suppressed by salt treatment. Salt treatment markedly increased cytokinin levels in roots but decreased them in shoots, resulting in a hormone distribution pattern similar to that in AGO2-overexpressing plants. These findings highlight the critical roles of the spatial distribution of cytokinins in both stress responses and grain development. Therefore, optimizing cytokinin distribution represents a promising strategy for improving both grain yield and stress tolerance in rice.

Diversification of plant agronomic traits by genome editing of brassinosteroid signaling family genes in rice.

Brassinosteroids (BRs) regulate various agronomic traits such as plant height, leaf angle, and grain size in rice (Oryza sativa L.); thus, BR signaling components are promising targets for molecular rational design. However, genetic materials for BR-signaling genes or family members remain limited in rice. Here, by genome editing using clustered regularly interspaced short palindromic repeats (CRSPR)/Cas9 tools, we generated a panel of single, double, triple, or quadruple mutants within three BR signaling gene families, including GSK3/SHAGGY-LIKE KINASE1 (GSK1)-GSK4, BRASSINAZOLE-RESISTANT1 (OsBZR1)-OsBZR4, and protein phosphatases with kelch-like (PPKL)1-PPKL3, under the same background (Zhonghua11, japonica). The high-order mutants were produced by either simultaneously targeting multiple sites on different genes of one family (GSKs and PPKLs) or targeting the overlapping sequences of family members (OsBZRs). The mutants exhibited a diversity of plant height, leaf angle, and grain morphology. Comparison analysis of the phenotypes together with BR sensitivity tests suggested the existence of functional redundancy, differentiation, or dominancy among the members within each family. In addition, we generated a set of transgenic plants overexpressing GSK2, OsBZR1/2, and PPKL2, respectively, in wild-type or activated forms with fusion of different tags, and also verified the protein response to BR application. Collectively, these plants greatly enriched the diversity of important agronomic traits in rice. We propose that editing of BR-related family genes could be a feasible approach for screening of desired plants to meet different requirements. Release of these materials as well as the related information also provides valuable resources for further BR research and utilization.

Association between depression and sleep quality in patients with systemic lupus erythematosus: a systematic review and meta-analysis.

BACKGROUND: Currently, there is no consistent understanding of the relationship between depression and sleep quality in patients with systemic lupus erythematosus (SLE). This study aimed to explore the correlation between depression and sleep quality in SLE patients. METHODS: Five English (PubMed, Web of Science, EMBASE, Cochrane Library, and CINAHL) databases were systematically searched from inception to January 12, 2021. Two authors independently screened publications and extracted data according to set inclusion and exclusion criteria. Statistical analyses were performed with STATA 16.0. Data were pooled using a random-effects model. RESULTS: A total of 9 identified studies matched the inclusion criteria, reporting on 514 patients with SLE in the analysis. A moderate correlation of depression with sleep quality was found (pooled r = 0.580 [0.473, 0.670]). Compared to good sleepers, patients with SLE and poor sleep quality had higher levels of depression (standardized mean difference = - 1.28 [- 1.87, - 0.69]). Depression was associated with subjective sleep quality (r = 0.332 [0.009, 0.592]), sleep latency (r = 0.412 [0.101, 0.649]), sleep disturbances (r = 0.405 [0.094, 0.645]), daytime dysfunction (r = 0.503 [0.214, 0.711]), the four dimensions of Pittsburgh Sleep Quality Index (PSQI), while no significant correlation was found in the other three PSQI dimensions. CONCLUSION: Depression had a moderate correlation with sleep quality in patients with SLE. Patients with poor sleep quality tended to have higher level of depression than that of good sleepers. Awareness of the correlation may help rheumatology physicians and nurses to assess and prevent depression and improve sleep quality in patients with SLE.

Photoelectric Bacteria Enhance the In Situ Production of Tetrodotoxin for Antitumor Therapy.

Engineered bacteria are promising bioagents to synthesize antitumor drugs at tumor sites with the advantages of avoiding drug leakage and degradation during delivery. Here, we report an optically controlled material-assisted microbial system by biosynthesizing gold nanoparticles (AuNPs) on the surface of Shewanella algae K3259 (S. algae) to obtain Bac@Au. Leveraging the dual directional electron transport mechanism of S. algae, the hybrid biosystem enhances in situ synthesis of antineoplastic tetrodotoxin (TTX) for a promising antitumor effect. Because of tumor hypoxia-targeting feature of facultative anaerobic S. algae, Bac@Au selectively target and colonize at tumor. Upon light irradiation, photoelectrons produced by AuNPs deposited on bacterial surface are transferred into bacterial cytoplasm and participate in accelerated cell metabolism to increase the production of TTX for antitumor therapy. The optically controlled material-assisted microbial system enhances the efficiency of bacterial drug synthesis in situ and provides an antitumor strategy that could broaden conventional therapy boundaries.

The divergence of brassinosteroid sensitivity between rice subspecies involves natural variation conferring altered internal auto-binding of OsBSK2.

Japonica/geng and indica/xian are two major rice (Oryza sativa) subspecies with multiple divergent traits, but how these traits are related and interact within each subspecies remains elusive. Brassinosteroids (BRs) are a class of steroid phytohormones that modulate many important agronomic traits in rice. Here, using different physiological assays, we revealed that japonica rice exhibits an overall lower BR sensitivity than indica. Extensive screening of BR signaling genes led to the identification of a set of genes distributed throughout the primary BR signaling pathway with divergent polymorphisms. Among these, we demonstrate that the C38/T variant in BR Signaling Kinase2 (OsBSK2), causing the amino acid change P13L, plays a central role in mediating differential BR signaling in japonica and indica rice. OsBSK2L13 in indica plays a greater role in BR signaling than OsBSK2P13 in japonica by affecting the auto-binding and protein accumulation of OsBSK2. Finally, we determined that OsBSK2 is involved in a number of divergent traits in japonica relative to indica rice, including grain shape, tiller number, cold adaptation, and nitrogen-use efficiency. Our study suggests that the natural variation in OsBSK2 plays a key role in the divergence of BR signaling, which underlies multiple divergent traits between japonica and indica.

GSK2 stabilizes OFP3 to suppress brassinosteroid responses in rice.

Brassinosteroids (BRs) are a class of phytohormones that modulate several important agronomic traits in rice (Oryza sativa). GSK2 is one of the critical suppressors of BR signalling and targets transcription factors such as OsBZR1 and DLT to regulate BR responses. Here, we identified OFP3 (OVATE FAMILY PROTEIN 3) as an interactor of both GSK2 and DLT by yeast-two-hybrid screening and demonstrated that OFP3 plays a distinctly negative role in BR responses. While knockout of OFP3 promoted rice seedling growth, overexpression of OFP3 led to strong BR insensitivity, which resulted in reduced plant height, leaf angle, and grain size. Interestingly, both BR biosynthetic and signalling genes had decreased expression in the overexpression plants. OFP3 overexpression also enhanced the phenotypes of BR-deficient mutants, but largely suppressed those of BR-enhanced plants. Moreover, treatment with either BR or bikinin, a GSK3-like kinase inhibitor, induced OFP3 depletion, whereas GSK2 or brassinazole, a BR synthesis inhibitor, promoted OFP3 accumulation. Furthermore, OFP3 exhibited transcription repressor activity and was able to interact with itself as well as additional BR-related components, including OFP1, OSH1, OSH15, OsBZR1, and GF14c. Importantly, GSK2 can phosphorylate OFP3 and enhance these interactions. We propose that OFP3, as a suppressor of both BR synthesis and signalling but stabilized by GSK2, incorporates into a transcription factor complex to facilitate BR signalling control, which is critical for the proper development of various tissues.

The CYB5R3c .350C>G and G6PD A alleles modify severity of anemia in malaria and sickle cell disease.

Genetic modifiers of anemia in Plasmodium falciparum infection and sickle cell disease (SCD) are not fully known. Both conditions are associated with oxidative stress, hemolysis and anemia. The CYB5R3 gene encodes cytochrome b5 reductase 3, which converts methemoglobin to hemoglobin through oxidation of NADH. CYB5R3c.350C > G encoding CYB5R3T117S , the most frequent recognized African-specific polymorphism, does not have known functional significance, but its high allele frequency (23% in African Americans) suggests a selection advantage. Glucose-6-phosphate dehydrogenase (G6PD) is essential for protection from oxidants; its African-polymorphic X-linked A+ and A- alleles, and other variants with reduced activity, coincide with endemic malaria distribution, suggesting protection from lethal infection. We examined the association of CYB5R3c.350C > G with severe anemia (hemoglobin <5 g/dL) in the context of G6PD A+ and A- status among 165 Zambian children with malaria. CYB5R3c.350C > G offered protection against severe malarial anemia in children without G6PD deficiency (G6PD wild type or A+/A- heterozygotes) (odds ratio 0.29, P = .022) but not in G6PD A+ or A- hemizygotes/homozygotes. We also examined the relationship of CYB5R3c.350C > G with hemoglobin concentration among 267 children and 321 adults and adolescents with SCD in the US and UK and found higher hemoglobin in SCD patients without G6PD deficiency (ß = 0.29, P = .022 children; ß = 0.33, P = .004 adults). Functional studies in SCD erythrocytes revealed mildly lower activity of native CYB5R3T117S compared to wildtype CYB5R3 and higher NADH/NAD+ ratios. In conclusion, CYB5R3c.350C > G appears to ameliorate anemia severity in malaria and SCD patients without G6PD deficiency, possibly accounting for CYB5R3c.350C > G selection and its high prevalence.

Effects of home-based lower limb resistance training on muscle strength and functional status in stable Chronic obstructive pulmonary disease patients.

AIMS AND OBJECTIVES: This study aimed to determine the effect of home-based lower limb resistance training (LLRT) in patients with stable COPD. BACKGROUND: Pulmonary rehabilitation (PR) in COPD patients has been substantially investigated, but the rehabilitation components differ among studies. Few works have focused on home-based LLRT. Furthermore, few studies have assessed muscle strength and functional status by isokinetic/isometric extensor muscle peak torque (PT) and five-repetition sit-to-stand test (FTSST), respectively. DESIGN: A randomised controlled design was adopted. METHODS: (i) The home-based LLRT consisted of six sets of lower limb training cycles by self-gravity resistance and Thera-band resistance at 8-12RM, 20-30 min/session and 3 sessions/week for 12 weeks. (ii) The intervention group (n = 25) received routine PR guidance and home-based LLRT, whereas the control group (n = 22) received routine PR guidance only. The muscle strengths, FTSST durations, 6-min walking distances (6MWDs) and COPD assessment test results at enrolment and week 12 were compared. RESULTS: Relative to the baseline findings, all the indexes of muscle strength (isometric extensor muscle PT, isometric extensor muscle PT to body weight ratio [PT/BW], isokinetic extensor muscle PT and isokinetic extensor muscle PT/BW) did not significantly change in the intervention group. Meanwhile, no significant intragroup difference was noted among the indexes of muscle strength (except for isometric extensor muscle PT) in the control group. The FTSST decrease was significant between and within groups. By contrast, the 6MWD significantly increased within both groups, but not between the groups. The COPD assessment tool score decreased significantly within the intervention group. CONCLUSIONS: Compared with routine PR guidance, home-based LLRT can improve not only the muscle strength and exercise endurance but also the lower limb functional status. RELEVANCE TO CLINICAL PRACTICE: Our developed home-based LLRT intervention is simple, safe and feasible in stable COPD patients and could hence be promoted in clinical practice.

WHITE PANICLE1, a Val-tRNA Synthetase Regulating Chloroplast Ribosome Biogenesis in Rice, Is Essential for Early Chloroplast Development.

Chloroplasts and mitochondria contain their own genomes and transcriptional and translational systems. Establishing these genetic systems is essential for plant growth and development. Here we characterized a mutant form of a Val-tRNA synthetase (OsValRS2) from Oryza sativa that is targeted to both chloroplasts and mitochondria. A single base change in OsValRS2 caused virescent to albino phenotypes in seedlings and white panicles at heading. We therefore named this mutant white panicle 1 (wp1). Chlorophyll autofluorescence observations and transmission electron microscopy analyses indicated that wp1 mutants are defective in early chloroplast development. RNA-seq analysis revealed that expression of nuclear-encoded photosynthetic genes is significantly repressed, while expression of many chloroplast-encoded genes also changed significantly in wp1 mutants. Western-blot analyses of chloroplast-encoded proteins showed that chloroplast protein levels were reduced in wp1 mutants, although mRNA levels of some genes were higher in wp1 than in wild type. We found that wp1 was impaired in chloroplast ribosome biogenesis. Taken together, our results show that OsValRS2 plays an essential role in chloroplast development and regulating chloroplast ribosome biogenesis.

ALR encoding dCMP deaminase is critical for DNA damage repair, cell cycle progression and plant development in rice.

Deoxycytidine monophosphate deaminase (dCMP deaminase, DCD) is crucial to the production of dTTP needed for DNA replication and damage repair. However, the effect of DCD deficiency and its molecular mechanism are poorly understood in plants. Here, we isolated and characterized a rice albinic leaf and growth retardation (alr) mutant that is manifested by albinic leaves, dwarf stature and necrotic lesions. Map-based cloning and complementation revealed that ALR encodes a DCD protein. OsDCD was expressed ubiquitously in all tissues. Enzyme activity assays showed that OsDCD catalyses conversion of dCMP to dUMP, and the ΔDCD protein in the alr mutant is a loss-of-function protein that lacks binding ability. We report that alr plants have typical DCD-mediated imbalanced dNTP pools with decreased dTTP; exogenous dTTP recovers the wild-type phenotype. A comet assay and Trypan Blue staining showed that OsDCD deficiency causes accumulation of DNA damage in the alr mutant, sometimes leading to cell apoptosis. Moreover, OsDCD deficiency triggered cell cycle checkpoints and arrested cell progression at the G1/S-phase. The expression of nuclear and plastid genome replication genes was down-regulated under decreased dTTP, and together with decreased cell proliferation and defective chloroplast development in the alr mutant this demonstrated the molecular and physiological roles of DCD-mediated dNTP pool balance in plant development.

Experience and nursing needs of school-age children undergoing lumbar puncture during the treatment of acute lymphoblastic leukaemia: a descriptive and qualitative study.

AIMS AND OBJECTIVES: To describe experiences and nursing needs of school-age Chinese children undergoing lumbar puncture for the treatment of acute lymphoblastic leukaemia. BACKGROUND: Lumbar puncture is an invasive procedure, causing psychological changes and physical discomfort in patients. In a previous study, it was proved that distraction intervention, such as music therapy, relieves pain and anxiety. There is limited evidence regarding the experience and needs of school-age children during lumbar puncture after being diagnosed with acute lymphoblastic leukaemia. To minimise their anxiety and pain during the procedure, it is important to collect information directly from these children. DESIGN: A descriptive qualitative research. METHODS: Twenty-one school-age children with acute lymphoblastic leukaemia participated in semi-structured interviews at a Children's Hospital in China. Data were collected by an experienced and trained interviewer. Qualitative content analysis was chosen to describe experiences of children undergoing lumbar puncture. RESULTS: While undergoing lumbar puncture for the treatment of acute lymphoblastic leukaemia, school-age Chinese children experienced complex psychological feelings (fear, tension, helplessness, sadness and anxiety). They also experienced physical discomfort. They had multipolar needs, such as information, communication, respect, self-actualisation, environment and equipment. CONCLUSIONS: This study identified important areas that must be closely monitored by healthcare staff, performing lumbar puncture on acute lymphoblastic leukaemia children. Thus, a successful and smooth procedure can be performed on these patients, and their quality of life can be improved. RELEVANCE TO CLINICAL PRACTICE: The experiences described in this study contribute to a better understanding of the needs of acute lymphoblastic leukaemia children undergoing lumbar puncture. They also provide valuable information to professional medical care staff that develops future nursing assessments.

WSL3, a component of the plastid-encoded plastid RNA polymerase, is essential for early chloroplast development in rice.

Plastid-encoded plastid RNA polymerase (PEP), a dominant RNA polymerase in mature chloroplasts, consists of core subunits and peripheral subunits. Despite the importance of the peripheral subunits in control of PEP activity it is unclear how they interact with one another to exert physiological effects on chloroplast development and plant growth, especially in rice. Here, we report a mutant, designated wsl3 that lacks a peripheral subunit in rice. We isolated the WSL3 gene encoding an essential peripheral subunit of rice PEP complex, OsPAP1/OspTAC3 by map-based cloning, and verified its function by complementation analysis. The wsl3 mutant showed a typical expression pattern of plastid-encoded genes, suggesting that PEP activity was impaired. Using immunofluorescent labeling and immunoblotting, we found that WSL3 was localized to the chloroplast and associated with the nucleoid. In addition, we demonstrated that WSL3 interacted with PEP subunits in Y2H, BiFC and pull-down experiments. Furthermore, a cpDNA IP assay revealed that WSL3 was associated with the PEP complex during the entire transcription process. We provide evidence suggesting that WSL3 is essential for early chloroplast development by interacting with subunits of the PEP complex.

Healing mechanism of cotton bandages loaded with PNIPAM/GO-Ag hydrogel on deep second-degree burn wounds in a rat model.

Dressings play a crucial role in the management of burn wounds. In this study, cotton bandages were modified with poly (N-isopropylacrylamide)/graphite oxide/nano silver (PNIPAM/GO-Ag) hydrogel to obtain a novel dressing (PNIPAM/GO-Ag/COT). The healing effect of the PNIPAM/GO-Ag/COT dressing on deep second-degree burn wounds in rats and the changes of related inflammatory factors were explored and analyzed systematically. The deep second-degree burn model was established by the steam scald method in Sprague-Dawley (SD) rats. The granulation tissue, collagen deposition, the expression of tumor necrosis factor-α (TNF-α), and basic fibroblast growth factor (bFGF) in the wound were evaluated by means of HE staining, Masson staining, ELISA, and immunohistochemistry methods. The results showed that, compared with the blank group (rats without the dressing treatment), the PNIPAM/GO-Ag/COT dressing reduced the expression of TNF-α by approximately 18 % and promoted the bFGF expression in wound tissue. Compared to the control group (rats with the gauze treatment), the wound healing rate in the PNIPAM/GO-Ag/COT dressing group was 58 % on the 14th day, with an increase of 30 %. These results demonstrated that the PNIPAM/GO-Ag/COT dressing primarily promoted burn wound healing by reducing inflammatory reactions, promoting collagen deposition, and enhancing the expression of bFGF.

The Association of Conventional Therapy Associated with Somatosensory Interactive Game Enhances the Effects of Early Pulmonary Rehabilitation for Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Randomized Controlled Trial.

Objective: This study aimed to evaluate the effect of somatosensory interactive games in combination with pulmonary rehabilitation programs (PRPs) on exercise tolerance, balance function, pulmonary function, inflammatory markers, and healthcare utilization in individuals with acute exacerbation of chronic obstructive pulmonary disease over 12 months. Design: In a randomized controlled trial, 80 patients were divided into two groups. The control group participated in a lasted 30 minutes daily program composed of postural training for 10 minutes, limb movement for 10 minutes, and breathing exercises for 10 minutes based on regular oxygen therapy and medication. The experimental group received a once-daily, 20-minute somatosensory interactive game session based on the control group. Patients began treatment within 48 hours after admission and lasted for 6 weeks. Results: The time × group interactions on 6-minute walk distance (6MWD) and Brief Balance Evaluation Systems Test (Brief-BESTest) between the two groups were significant (P < 0.001). At the postintervention and each time point of follow-up, the 6-minute walk distance (6MWD) and Brief-BESTest of the intervention group were significantly higher than those of the control group (P < 0.05). The effects of time factor on forced expiratory volume in one second and forced vital capacity were statistically significant (P < 0.05). The 6MWD and Brief-BESTest of the intervention group peaked 3 months after the intervention and were higher than the control group within 12 months. C-reactive protein and procalcitonin were similar between the groups before and after intervention (P > 0.05). The readmission rates and mean length of time spent in the hospital were comparable between the groups at 12 months (P > 0.05). Conclusions: The addition of somatosensory interactive games based on a PRP was safe and feasible, and this benefit persisted for 12 months, peaked at 3 months after the intervention, and then gradually decreased.

Reliability, Validity, Modification and Expansion of the Chinese Version of the Disease-Specific Anxiety Questionnaire for Chronic Obstructive Pulmonary Disease.

Purpose: To translate a disease-specific anxiety questionnaire on chronic obstructive pulmonary disease (COPD) and test its reliability and validity in China. Patients and Methods: The German version of the revised COPD Anxiety Questionnaire (CAF-R) was initially validated using step-by-step translation, back-translation, and cross-cultural adaptation. The reliability and validity of the Chinese version of the CAF-R (CAF-R-CN) were tested among 448 patients with COPD (mean age =71.42±9.33 years, 17.2% female) from four medical institutions in Suzhou, Jiangsu Province, using convenience sampling, from April 2022 to June 2023. Results: The CAF-R-CN included six dimensions with a total of 25 items. The item-level content validity index was 0.860-1.000; the scale-level content validity index was 0.920. The structural validity χ2/df was 2.326, the root mean square error of approximation was 0.077, the comparative fit index was 0.924, and the Tucker-Lewis index was 0.912. The six-dimensional internal consistency index Cronbach's α coefficient was 0.696-0.910, and the test-retest reliability was 0.949. An optimal cut-off score of 50.5 was selected with a sensitivity of 0.786 and specificity of 0.870. Conclusion: The CAF-R-CN had satisfactory reliability and validity and can be used to identify and assess anxiety in COPD patients with a Chinese cultural background.

Polymeric nanoformulations aimed at cancer metabolism reprogramming with high specificity to inhibit tumor growth.

Metabolic disorders of cancer cells create opportunities for metabolic interventions aimed at selectively eliminating cancer cells. Nevertheless, achieving this goal is challenging due to cellular plasticity and metabolic heterogeneity of cancer cells. This study presents a dual-drug-loaded, macrophage membrane-coated polymeric nanovesicle designed to reprogram cancer metabolism with high specificity through integrated extracellular and intracellular interventions. This nanoformulation can target cancer cells and largely reduce their glucose intake, while the fate of intracellular glucose internalized otherwise is redirected at the specially introduced oxidation reaction instead of inherent cancer glycolysis. Meanwhile, it inhibits cellular citrate intake, further reinforcing metabolic intervention. Furthermore, the nanoformulation causes not only H2O2 production, but also NADPH down-regulation, intensifying redox damage to cancer cells. Consequently, this nanoformulation displays highly selective toxicity to cancer cells and minimal harm to normal cells mainly due to metabolic vulnerability of the former. Once administered into tumor-bearing mice, this nanoformulation is found to induce the transformation of pro-tumor tumor associated macrophages into the tumor-suppressive phenotype and completely inhibit tumor growth with favourable biosafety.

Oral Saccharomyces cerevisiae-Guided Enzyme Prodrug Therapy Combined with Immunotherapy for the Treatment of Orthotopic Colorectal Cancer.

Colorectal cancer (CRC) is a major global health concern, and the development of effective treatment strategies is crucial. Enzyme prodrug therapy (EPT) shows promise in combating tumors but faces challenges in achieving sustained expression of therapeutic enzymes and optimal biological distribution. To address these issues, a fungi-triggered in situ chemotherapeutics generator (named as SC@CS@5-FC) was constructed via oral delivery of a prodrug (5-fluorocytosine, 5-FC) for the treatment of orthotopic colorectal tumor. When SC@CS@5-FC targets the tumor through tropism by Saccharomyces cerevisiae (SC), the chemotherapeutic generator could be degraded under abundant hyaluronidase (HAase) in the tumor microenvironment by an enzyme-responsive gate to release prodrug (5-FC). And nontoxic 5-FC was catalyzed to toxic chemotherapy drug 5-fluorouracil (5-FU) by cytosine deaminase (CD) of SC. Meanwhile, SC and zinc-coordinated chitosan nanoparticles could be used as immune adjuvants to activate antigen-presenting cells and further enhance the therapeutic effect. Our results demonstrated that SC@CS@5-FC could effectively inhibit tumor growth and prolong mouse survival in an orthotopic colorectal cancer model. This work utilizes living SC as a dynamotor and positioning system for the chemotherapeutic generator SC@CS@5-FC, providing a strategy for oral enzyme prodrug therapy for the treatment of orthotopic colorectal.