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1.
Cell Rep Med ; 5(6): 101592, 2024 Jun 18.
Article En | MEDLINE | ID: mdl-38843841

Environmental lipids are essential for fueling tumor energetics, but whether these exogenous lipids transported into cancer cells facilitate immune escape remains unclear. Here, we find that CD36, a transporter for exogenous lipids, promotes acute myeloid leukemia (AML) immune evasion. We show that, separately from its established role in lipid oxidation, CD36 on AML cells senses oxidized low-density lipoprotein (OxLDL) to prime the TLR4-LYN-MYD88-nuclear factor κB (NF-κB) pathway, and exogenous palmitate transfer via CD36 further potentiates this innate immune pathway by supporting ZDHHC6-mediated MYD88 palmitoylation. Subsequently, NF-κB drives the expression of immunosuppressive genes that inhibit anti-tumor T cell responses. Notably, high-fat-diet or hypomethylating agent decitabine treatment boosts the immunosuppressive potential of AML cells by hijacking CD36-dependent innate immune signaling, leading to a dampened therapeutic effect. This work is of translational interest because lipid restriction by US Food and Drug Administration (FDA)-approved lipid-lowering statin drugs improves the efficacy of decitabine therapy by weakening leukemic CD36-mediated immunosuppression.


CD36 Antigens , Decitabine , Leukemia, Myeloid, Acute , Lipid Metabolism , Lipoproteins, LDL , CD36 Antigens/metabolism , CD36 Antigens/genetics , Humans , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/immunology , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/pathology , Lipid Metabolism/drug effects , Decitabine/pharmacology , Decitabine/therapeutic use , Lipoproteins, LDL/metabolism , Animals , NF-kappa B/metabolism , Cell Line, Tumor , Myeloid Differentiation Factor 88/metabolism , Myeloid Differentiation Factor 88/genetics , Mice , Signal Transduction/drug effects , Tumor Escape/drug effects , Drug Resistance, Neoplasm/drug effects , Toll-Like Receptor 4/metabolism , Acyltransferases/genetics , Immunity, Innate/drug effects , Mice, Inbred C57BL
3.
Nurs Open ; 11(4): e2163, 2024 Apr.
Article En | MEDLINE | ID: mdl-38642075

AIM: To determine the relationship between psychological resilience, nursing practice environment, and moral courage of clinical nurses and also the factors influencing moral courage. DESIGN: Cross-sectional study. METHODS: 586 nurses from a general hospital were selected by convenience sampling method in January 2023. The general information questionnaire, Nurses' Moral Courage Scale (NMCS), Resilience Scale, and Practice Environment Scale (PES) were measured. Hierarchical linear regression analysis was used to explore the influencing factors of clinical nurses' moral courage. RESULTS: Nurses' average moral courage score was 79.00 (69.00, 91.00). The nurses' moral courage was positively correlated with psychological resilience and nursing practice environment. Multivariate linear regression analysis showed that psychological resilience and nursing practice environment entered the regression equation, accounting for 23.4% of the total variation. Psychological resilience and nursing practice environment are the main factors affecting the moral courage of clinical nurses. Nursing managers should conduct moral courage training, develop a decent nursing practice environment, pay attention to the psychological emotions of nurses, and actively build a safe, open, and supportive atmosphere for moral behaviour.


Courage , Nurse Administrators , Resilience, Psychological , Humans , Cross-Sectional Studies , Morals
4.
J Hematol Oncol ; 17(1): 23, 2024 Apr 24.
Article En | MEDLINE | ID: mdl-38659046

BACKGROUND: The autologous anti-B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy LCAR-B38M has been approved for the treatment of relapsed and refractory multiple myeloma in many countries across the world under the name ciltacabtagene autoleucel. LEGEND-2 was the first-in-human trial of LCAR-B38M and yielded deep and durable therapeutic responses. Here, we reported the outcomes in LEGEND-2 after a minimal 5-year follow-up. METHODS: Participants received an average dose of 0.5 × 106 cells/kg LCAR-B38M in split or single unfractionated infusions after cyclophosphamide-based lymphodepletion therapy. Investigator-assessed response, survival, safety and pharmacokinetics were evaluated. RESULTS: Seventy-four participants enrolled and had a median follow-up of 65.4 months. The 5-year progression-free survival (PFS) and overall survival (OS) rates were 21.0% and 49.1%, with progressive flattening of the survival curves over time. Patients with complete response (CR) had longer PFS and OS, with 5-year rates of 28.4% and 65.7%, respectively. Twelve patients (16.2%) remained relapse-free irrespective of baseline high-risk cytogenetic abnormality and all had normal humoral immunity reconstituted. An ongoing CR closely correlated with several prognostic baseline indices including favorable performance status, immunoglobulin G subtype, and absence of extramedullary disease, as well as a combination cyclophosphamide and fludarabine preconditioning strategy. Sixty-two (83.8%) suffered progressive disease (PD) and/or death; however, 61.1% of PD patients could well respond to subsequent therapies, among which, the proteasome inhibitor-based regimens benefited the most. Concerning the safety, hematologic and hepatic function recovery were not significantly different between non-PD and PD/Death groups. A low rate of second primary malignancy (5.4%) and no severe virus infection were observed. The patients who tested positive for COVID-19 merely presented self-limiting symptoms. In addition, a sustainable CAR T population of one case with persistent remission was delineated, which was enriched with indolently proliferative and lowly cytotoxic CD4/CD8 double-negative functional T lymphocytes. CONCLUSIONS: These data, representing the longest follow-up of BCMA-redirected CAR T-cell therapy to date, demonstrate long-term remission and survival with LCAR-B38M for advanced myeloma. TRIAL REGISTRATION: LEGEND-2 was registered under the trial numbers NCT03090659, ChiCTRONH-17012285.


B-Cell Maturation Antigen , Immunotherapy, Adoptive , Multiple Myeloma , Adult , Aged , Female , Humans , Male , Middle Aged , B-Cell Maturation Antigen/immunology , Follow-Up Studies , Immunotherapy, Adoptive/methods , Immunotherapy, Adoptive/adverse effects , Multiple Myeloma/therapy , Multiple Myeloma/mortality , Receptors, Chimeric Antigen/therapeutic use , Receptors, Chimeric Antigen/immunology , Remission Induction , Survival Rate
5.
Signal Transduct Target Ther ; 9(1): 62, 2024 Mar 06.
Article En | MEDLINE | ID: mdl-38448403

Natural killer T cell lymphoma (NKTCL) is highly aggressive, with advanced stage patients poorly responding to intensive chemotherapy. To explore effective and safe treatment for newly diagnosed advanced stage NKTCL, we conducted a phase II study of anti-metabolic agent pegaspargase plus PD-1 antibody sintilimab (NCT04096690). Twenty-two patients with a median age of 51 years (range, 24-74) were enrolled and treated with induction treatment of pegaspargase 2500 IU/m2 intramuscularly on day 1 and sintilimab 200 mg intravenously on day 2 for 6 cycles of 21 days, followed by maintenance treatment of sintilimab 200 mg for 28 cycles of 21 days. The complete response and overall response rate after induction treatment were 59% (95%CI, 43-79%) and 68% (95%CI, 47-84%), respectively. With a median follow-up of 30 months, the 2 year progression-free and overall survival rates were 68% (95%CI, 45-83%) and 86% (95%CI, 63-95%), respectively. The most frequently grade 3/4 adverse events were neutropenia (32%, n = 7) and hypofibrinogenemia (18%, n = 4), which were manageable and led to no discontinuation of treatment. Tumor proportion score of PD-L1, peripheral blood high-density lipoprotein cholesterol, and apolipoprotein A-I correlated with good response, while PD-1 on tumor infiltrating lymphocytes and peripheral Treg cells with poor response to pegaspargase plus sintilimab treatment. In conclusion, the chemo-free regimen pegaspargase plus sintilimab was effective and safe in newly diagnosed, advanced stage NKTCL. Dysregulated lipid profile and immunosuppressive signature contributed to treatment resistance, providing an alternative therapeutic approach dual targeting fatty acid metabolism and CTLA-4 in NKTCL.


Antibodies, Monoclonal, Humanized , Asparaginase , Lymphoma , Natural Killer T-Cells , Polyethylene Glycols , Humans , Programmed Cell Death 1 Receptor , Adult , Middle Aged , Aged , Young Adult
6.
Adv Mater ; 36(11): e2310177, 2024 Mar.
Article En | MEDLINE | ID: mdl-38069449

Droplet impact is a ubiquitous liquid behavior that closely tied to human life and production, making indispensable impacts on the big world. Nature-inspired superhydrophobic surfaces provide a powerful platform for regulating droplet impact dynamics. The collision between classic phenomena of droplet impact and the advanced manufacture of superhydrophobic surfaces is lighting up the future. Accurately understanding, predicting, and tailoring droplet dynamic behaviors on superhydrophobic surfaces are progressive steps to integrate the droplet impact into versatile applications and further improve the efficiency. In this review, the progress on phenomena, mechanisms, regulations, and applications of droplet impact on superhydrophobic surfaces, bridging the gap between droplet impact, superhydrophobic surfaces, and engineering applications are comprehensively summarized. It is highlighted that droplet contact and rebound are two focal points, and their fundamentals and dynamic regulations on elaborately designed superhydrophobic surfaces are discussed in detail. For the first time, diverse applications are classified into four categories according to the requirements for droplet contact and rebound. The remaining challenges are also pointed out and future directions to trigger subsequent research on droplet impact from both scientific and applied perspectives are outlined. The review is expected to provide a general framework for understanding and utilizing droplet impact.

7.
Chinese Pharmacological Bulletin ; (12): 461-468, 2024.
Article Zh | WPRIM | ID: wpr-1013638

Aim To research the neuroprotective effect of Haikun Shenxi (HKSX) medicated serum on N2a/ App695 cells and the underlying mechanism. Methods HKSX medicated serum was prepared and carbohydrate components in it was analyzed using high performance thin layer chromatography (HPTLC) . N2a/ App695 cells were intervened with HKSX medicated serum, the cytotoxicity of HKSX medicated serum was measured by MTT; AP[_

8.
Sci Bull (Beijing) ; 68(21): 2607-2619, 2023 11 15.
Article En | MEDLINE | ID: mdl-37798178

Epstein-Barr virus (EBV) is the oncogenic driver of multiple cancers. However, the underlying mechanism of virus-cancer immunological interaction during disease pathogenesis remains largely elusive. Here we reported the first comprehensive proteogenomic characterization of natural killer/T-cell lymphoma (NKTCL), a representative disease model to study EBV-induced lymphomagenesis, incorporating genomic, transcriptomic, and in-depth proteomic data. Our multi-omics analysis of NKTCL revealed that EBV gene pattern correlated with immune-related oncogenic signaling. Single-cell transcriptome further delineated the tumor microenvironment as immune-inflamed, -deficient, and -desert phenotypes, in association with different setpoints of cancer-immunity cycle. EBV interacted with transcriptional factors to provoke GPCR interactome (GPCRome) reprogramming. Enhanced expression of chemokine receptor-1 (CCR1) on malignant and immunosuppressive cells modulated virus-cancer interaction on microenvironment. Therapeutic targeting CCR1 showed promising efficacy with EBV eradication, T-cell activation, and lymphoma cell killing in NKTCL organoid. Collectively, our study identified a previously unknown GPCR-mediated malignant progression and translated sensors of viral molecules into EBV-specific anti-cancer therapeutics.


Epstein-Barr Virus Infections , Lymphoma , Natural Killer T-Cells , Humans , Herpesvirus 4, Human/genetics , Epstein-Barr Virus Infections/complications , Proteomics , Lymphoma/complications , Natural Killer T-Cells/pathology , Tumor Microenvironment/genetics
9.
Adv Mater ; 35(35): e2302038, 2023 Sep.
Article En | MEDLINE | ID: mdl-37199373

Sorption-based atmospheric water harvesting (AWH) is a promising approach for mitigating worldwide water scarcity. However, reliable water supply driven by sustainable energy regardless of diurnal variation and weather remains a long-standing challenge. To address this issue, a polyelectrolyte hydrogel sorbent with an optimal hybrid-desorption multicyclic-operation strategy is proposed, achieving all-day AWH and a significant increase in daily water production. The polyelectrolyte hydrogel possesses a large interior osmotic pressure of 659 atm, which refreshes sorption sites by continuously migrating the sorbed water within its interior, and thus enhancing sorption kinetics. The charged polymeric chains coordinate with hygroscopic salt ions, anchoring the salts and preventing agglomeration and leakage, thereby enhancing cyclic stability. The hybrid desorption mode, which couples solar energy and simulated waste heat, introduces a uniform and adjustable sorbent temperature for achieving all-day ultrafast water release. With rapid sorption-desorption kinetics, an optimization model suggests that eight moisture capture-release cycles are capable of achieving high water yield of 2410 mLwater kgsorbent -1 day-1 , up to 3.5 times that of single-cyclic non-hybrid modes. The polyelectrolyte hydrogel sorbent and the coupling with sustainable energy driven desorption mode pave the way for the next-generation AWH systems, significantly bringing freshwater on a multi-kilogram scale closer.

10.
Chem Commun (Camb) ; 59(19): 2739-2742, 2023 Mar 02.
Article En | MEDLINE | ID: mdl-36744593

A family of planar chiral indene-fused ferrocenes were prepared through an intramolecular asymmetric C-H arylation in excellent yields (up to 99%) with excellent enantioselectivities (up to 99% ee). They were thereafter successfully transformed to chiral ferrocenyl phosphines, featuring both planar and central chiralities, in good yields (up to 83%) and excellent diastereoselectivities (up to 99% de) through highly diastereoselective phosphination. This protocol offers a general method for planar and central chiral ferrocenyl phosphines. The potential applications of the newly developed ligands were demonstrated by a Pd-catalyzed enantioselective allylic alkylation reaction, in which high enantioselectivity (92% ee) and good yield (89%) were obtained.

11.
Comput Biol Med ; 155: 106637, 2023 03.
Article En | MEDLINE | ID: mdl-36791549

BACKGROUND: Hyperuricemia is a more popular metabolic disease caused by a disorder of purine metabolism. Our previous study firstly screened out a natural product Isobavachin as anti-hyperuricemia targeted hURAT1 from a Chinese medicine Haitongpi (Cortex Erythrinae). In view of Isobavachin's diverse pharmacological activities, similar to the Tranilast (as another hURAT1 inhibitor), our study focused on its potential targets and molecular mechanisms of Isobavachin anti-hyperuricemia based on network pharmacology and molecular docking. METHODS: First of all, the putative target genes of compounds were screen out based on the public databases with different methods, such as SwissTargetPerdiction, PharmMapper and TargetNet,etc. Then the compound-pathways were obtained by the compounds' targets gene from David database for Gene Ontology (GO) function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analysis. The cross pathways of compound-pathways and the diseases pathways of hyperuricemia from Comparative Toxicogenomics Database were be considered as the compound-disease pathways. Next, based on the compound-disease pathways and the PPI network, the core targets were identified based on the retrieved disease-genes. Finally, the compound-target-pathway-disease network was constructed by Cytoscape and the mechanism of isobavachin anti-hyperuricemia was discussed based on the network analysis. RESULTS: Our study demonstrated that there were five pathways involved in Isobavachin against hyperuricemia, including Drug metabolism-other enzymes, Metabolic pathways, Bile secretion, Renin-angiotensin system and Renin secretion. Among the proteins involved in these pathways, HPRT1, REN and ABCG2 were identified as the core targets associated with hyperuricemia, which regulated the five pathways mentioned above. It is quite different from that of Tranilast, which involved in the same pathways except Bile secretion instead of purine metabolism. CONCLUSION: This study revealed Isobavachin could regulate the pathways including Drug metabolism-other enzymes, Metabolic pathways, Bile secretion, Renin-angiotensin system, Renin secretion by core targets HPRT1, REN and ABCG2, in the treatment of hyperuricemia effect. Among them, the Bile secretion regulated by ABCG2 probably would be a novel pathway. Our work provided a theoretical basis for the pharmacological study of Isobavachin in lowering uric acid and further basic research.


Drugs, Chinese Herbal , Network Pharmacology , Molecular Docking Simulation , Renin , Purines , Medicine, Chinese Traditional
12.
Chinese Journal of Biotechnology ; (12): 1759-1772, 2023.
Article Zh | WPRIM | ID: wpr-981168

Bacillus cereus is a common foodborne pathogen. Accidently eating food contaminated by B. cereus will cause vomiting or diarrhea, and even death in severe cases. In the present study, a B. cereus strain was isolated from spoiled rice by streak culture. The pathogenicity and drug resistance of the isolated strain were analyzed by drug sensitivity test and PCR amplification of virulence-associated gene respectively. Cultures of the purified strain were injected intraperitoneally into mice to examine their effects on intestinal immunity-associated factors and gut microbial communities, to provide references for the pathogenic mechanism and medication guidance of these spoilage microorganisms. The results showed that the isolated B. cereus strain was sensitive to norfloxacin, nitrofurantoin, tetracycline, minocycline, ciprofloxacin, spectinomycin, clindamycin, erythrocin, clarithromycin, chloramphenicol, levofloxacin, and vancomycin, but resistant to bactrim, oxacillin and penicillin G. The strain carries seven virulence-associated genes including hblA, hblC, hblD, nheA, nheB, nheC and entFM, which are involved in diarrhea-causing toxins production. After infecting mice, the isolated B. cereus strain was found to cause diarrhea in mice, and the expression levels of immunoglobulins and inflammatory factors in the intestinal mucosae of the challenged mice were significantly up-regulated. Gut microbiome analysis showed that the composition of gut microbial community in mice changed after infection with B. cereus. The abundance of the uncultured_bacterium_f_Muribaculaceae in Bacteroidetes, which is a marker of body health, was significantly decreased. On the other hand, the abundance of uncultured_bacterium_f_Enterobacteriaceae, which is an opportunistic pathogen in Proteobacteria and a marker of dysbacteriosis, was significantly increased and was significantly positively correlated with the concentrations of IgM and IgG. These results showed that the pathogenic B. cereus carrying diarrhea type virulence-associated gene can activate the immune system by altering the composition of gut microbiota upon infection.


Animals , Mice , Bacillus cereus/metabolism , Food Microbiology , Immunity, Mucosal , Diarrhea , Microbiota , Enterotoxins/genetics
13.
Chinese Journal of Endemiology ; (12): 398-400, 2023.
Article Zh | WPRIM | ID: wpr-991643

Objective:To understand the results of serum protein electrophoresis in patients with acute brucellosis, and to provide objective indicators for clinical diagnosis and treatment of acute brucellosis patients.Methods:Thirty acute brucellosis patients diagnosed by the Center for Disease Prevention and Control of Donghe District, Baotou City from January to June 2021 were selected as the case group, and 30 local healthy persons who took physical examination during the same period were selected as the control group. Blood samples were collected from the two groups of people, serum was separated and serum protein electrophoresis was performed. Independent sample t-tests were used to compare total protein concentrations, protein fractions (albumin, α1-globulin, α2-globulin, β-globulin and γ-globulin) and albumin/globulin (A/G) ratio. Results:The age of patients in the case group was (52.35 ± 6.74) years old, with 25 males and 5 females. The course of the disease ranged from 0.3 to 2.6 months, with an average of 1.78 months. The age of people in the control group was (52.74 ± 5.47) years old, with 25 males and 5 females. There were no statistically significant difference in age and sex distuibution between the two groups ( P > 0.05). The concentrations of total protein and α2-globulin fractions were not significantly different between the two groups ( t = 0.78, 2.04, P > 0.05, respectively). Compared with the control group, the differences in the percentage of albumin, α1-globulin, β-globulin, γ-globulin in total protein and A/G ratio were statistically significant ( t = 4.78, 4.76, 2.89, 2.20, 3.65, P < 0.05). Conclusions:The percentage of serum albumin in total protein and A/G ratio decrease in patients with acute brucellosis, while the percentage of α1-globulin, β-globulin and γ-globulin in total protein increase. The percentage of albumin, α1-globulin, β-globulin, γ-globulin in total protein and A/G ratio can be uesed as objective indicators for clinical treatment of acute brucellosis.

14.
Article Zh | WPRIM | ID: wpr-990523

Objective:To search and summarize the evidence for the non-pharmacological management of delirium of critically ill patients in PICU, and to provide evidence-based guidance for clinical practice.Methods:According to the "6S" evidence pyramid model, we searched computerized decision support system, websites of guidelines, and databases, and obtained the guidelines, clinical decisions, systematic reviews, and evidence summaries.After screening the articles, two researchers independently appraise articles using validated tools, and finally formed the evidence summary of delirium non-pharmacological management of critically ill patients in PICU.Results:Totally six articles were included for the evidence synthesis, including three guidelines, two systematic reviews, and one expert advice.Twenty pieces of evidence including four aspects were summarized, namely delirium screening, risk prediction, non-pharmacological prevention and management strategies, health care provider education and departmental standardization.Conclusion:The evidence summarized in this study can provide a reference to health care professionals.When we apply this evidence in the clinical setting, we should adapt it accordingly to the specific clinical setting to improve the effectiveness of the evidence.

15.
Chinese Pharmacological Bulletin ; (12): 1127-1135, 2023.
Article Zh | WPRIM | ID: wpr-1013790

Aim To study the synergistic effect of withaferin A (WA) combined with cisplatin (DDP) on cervical cancer and its mechanism. Methods MTT assay was employed to detect the synergistic effect of WA on DDP in cervical cancer cell lines. Annexin V-FITC/PI staining, TUNEL assay and immunoblotting were used to investigate the effect of WA combined with DDP on apoptosis of cervical cancer cells. Immunofluorescence and immunoblotting were used to detect NF-kB/MDR1 pathway related proteins. DCFH-DA and MitoSOX were applied to determine the intracellular reactive oxygen species (ROS) levels. A xenograft model was also used to evaluate the synergistic effect of WA on DDP. Results The combination of WA and DDP could inhibit the survival of cervical cancer cells, promote apoptosis, and inhibit the growth of tumor in mice. WA could inhibit DDP-induced NF-kB/MDR1 signaling pathway and promote ROS production. Conclusions WA plays a synergistic role in anti-cervical cancer by inhibiting DDP-induced NF-kB/MDR1 pathway activation and enhancing DDP induced ROS production.

16.
Cell Death Discov ; 8(1): 495, 2022 Dec 22.
Article En | MEDLINE | ID: mdl-36550096

KDM5C is a histone H3K4-specific demethylase, which has been shown to play a key role in biological disease and development. However, the role of KDM5C in trophoblasts at early pregnancy is currently unknown. Here, we showed that KDM5C was upregulated in placental trophoblasts from recurrent miscarriage (RM) patients compared with healthy controls (HCs). Trophoblast proliferation and invasion was inhibited by KDM5C overexpression and was promoted by KDM5C knockdown. Transcriptome sequencing revealed that elevated KDM5C exerted anti-proliferation and anti-invasion effects by repressing the expression of essential regulatory genes. The combination analysis of RNA-seq, ChIP-seq and CUT&Tag assay showed that KDM5C overexpression leads to the reduction of H3K4me3 on the promoters and the corresponding downregulation of expression of several regulatory genes in trophoblasts. Among these genes, TGFß2 and RAGE are essential for the proliferation and invasion of trophoblasts. Importantly, overexpression of KDM5C by a systemically delivered KDM5C adenovirus vector (Ad-KDM5C) promoted embryo resorption rate in mouse. Our results support that KDM5C is an important regulator of the trophoblast function during early pregnancy, and suggesting that KDM5C activity could be responsible for epigenetic alterations seen RM disease.

17.
Nat Commun ; 13(1): 5406, 2022 09 15.
Article En | MEDLINE | ID: mdl-36109494

Sorption-based atmospheric water harvesting has the potential to realize water production anytime, anywhere, but reaching a hundred-gram high water yield in semi-arid climates is still challenging, although state-of-the-art sorbents have been used. Here, we report a portable and modularized water harvester with scalable, low-cost, and lightweight LiCl-based hygroscopic composite (Li-SHC) sorbents. Li-SHC achieves water uptake capacity of 1.18, 1.79, and 2.93 g g-1 at 15%, 30%, and 60% RH, respectively. Importantly, considering the large mismatch between water capture and release rates, a rationally designed batch processing mode is proposed to pursue maximum water yield in a single diurnal cycle. Together with the advanced thermal design, the water harvester shows an exceptional water yield of 311.69 g day-1 and 1.09 g gsorbent-1 day-1 in the semi-arid climate with the extremely low RH of ~15%, demonstrating the adaptability and possibility of achieving large-scale and reliable water production in real scenarios.


Desert Climate , Water
18.
FASEB J ; 36(10): e22562, 2022 10.
Article En | MEDLINE | ID: mdl-36125067

Oncoprotein AML1-ETO (AE) derived from t(8;21)(q22;q22) translocation is typically present in a portion of French-American-British-M2 subtype of acute myeloid leukemia (AML). Although these patients have relatively favorable prognoses, substantial numbers of them would relapse after conventional therapy. Here, we explored whether reinforcing the endogenous differentiation potential of t(8;21) AML cells would diminish the associated malignancy. In doing so, we noticed an expansion of immature erythroid blasts featured in both AML1-ETO9a (AE9a) and AE plus c-KIT (N822K) (AK) murine leukemic models. Interestingly, in the AE9a murine model, a spontaneous step-wise erythroid differentiation path, as characterized by the differential expression of CD43/c-Kit and the upregulation of several key erythroid transcription factors (TFs), accompanied the decline or loss of leukemia-initiating potential. Notably, overexpression of one of the key erythroid TFs, Ldb1, potently disrupted the repopulation of AE9a leukemic cells in vivo, suggesting a new promising intervention strategy of t(8;21) AML through enforcing their erythroid differentiation.


Leukemia, Myeloid, Acute , Oncogene Proteins, Fusion , Animals , Chromosomes, Human, Pair 21 , Chromosomes, Human, Pair 8 , DNA-Binding Proteins/metabolism , Humans , LIM Domain Proteins , LIM-Homeodomain Proteins , Leukemia, Myeloid, Acute/metabolism , Mice , Oncogene Proteins, Fusion/genetics , Oncogene Proteins, Fusion/metabolism , RUNX1 Translocation Partner 1 Protein/genetics , Translocation, Genetic
19.
Acta Cir Bras ; 37(4): e370408, 2022.
Article En | MEDLINE | ID: mdl-35857936

PURPOSE: To explore the effect of different gastrointestinal reconstruction techniques on laparoscopic distal gastrectomy of gastric cancer on the nutritional and anemia status, and quality of life (QoL) of patients. METHODS: Eligible patients were randomly divided into three groups (n=36/group): Billroth I anastomosis group, Billroth II combined with Braun anastomosis group, and Roux-en-Y anastomosis group. Related indicators were compared and analyzed. RESULTS: The general data were comparable among the three groups (all P>0.05). Among the surgical-related indicators and postoperative recovery indicators, only the comparison of the operation time was statistically significant (P=0.004). The follow-up time was 5~36 months (average 27.9 months). In terms of nutritional and anemia indicators, only the differences in the levels of prealbumin, hemoglobin and serum ferritin in 24 months after operation showed significant differences (P=0.015, P=0.003, P=0.005, respectively). There were no significant differences in hospital readmission rate, overall survival, and QoL among the three groups (all P>0.05). CONCLUSIONS: In laparoscopic gastrectomy for stage II~III distal gastric cancer, Billroth I anastomosis has shorter operation time than Billroth II combined with Braun anastomosis and Roux-en-Y anastomosis and advantages in the improvement of nutritional status and anemia recovery.


Anemia , Laparoscopy , Stomach Neoplasms , Anastomosis, Roux-en-Y/methods , Anemia/surgery , Gastrectomy/methods , Gastroenterostomy , Humans , Laparoscopy/methods , Nutritional Status , Postoperative Complications , Quality of Life , Stomach Neoplasms/surgery , Treatment Outcome
20.
Sci Rep ; 12(1): 10139, 2022 06 16.
Article En | MEDLINE | ID: mdl-35710740

Precise customer requirements acquisition is the primary stage of product conceptual design, which plays a decisive role in product quality and innovation. However, existing customer requirements mining approaches pay attention to the offline or online customer comment feedback and there has been little quantitative analysis of customer requirements in the analogical reasoning environment. Latent and innovative customer requirements can be expressed by analogical inspiration distinctly. In response, this paper proposes a semantic analysis-driven customer requirements mining method for product conceptual design based on deep transfer learning and improved latent Dirichlet allocation (ILDA). Initially, an analogy-inspired verbal protocol analysis experiment is implemented to obtain detailed customer requirements descriptions of elevator. Then, full connection layers and a softmax layer are added to the output-end of Chinese bidirectional encoder representations from Transformers (BERT) pre-training language model. The above deep transfer model is utilized to realize the customer requirements classification among functional domain, behavioral domain and structural domain in the customer requirement descriptions of elevator by fine-tuning training. Moreover, the ILDA is adopted to mine the functional customer requirements that can represent customer intention maximally. Finally, an effective accuracy of customer requirements classification is acquired by using the BERT deep transfer model. Meanwhile, five kinds of customer requirements of elevator and corresponding keywords as well as their weight coefficients in the topic-word distribution are extracted. This work can provide a novel research perspective on customer requirements mining for product conceptual design through natural language processing.


Algorithms , Semantics , Language , Natural Language Processing , Problem Solving
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