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1.
Hematology ; 29(1): 2350319, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38748459

ABSTRACT

OBJECTIVES: The purpose of this study was to compare the effectiveness of the combination of venetoclax and hypomethylating agents with the HAG regimen. METHODS: We studied 52 cases of newly diagnosed AML and 26 cases of relapsed refractory AML, (including AML patients with treatment-related and ELN-adverse risk disease (n = 50)). These patients were treated with venetoclax and hypomethylating agents and HAG regimens, respectively. RESULTS: Twenty-nine patients newly diagnosed with acute myeloid leukemia were treated with VEN-HMA (venetoclax-hypomethylating agent), while 23 patients were treated with HAG. The median age of the VEN-HMA group was 70 years, while the HAG group had a median age of 69 years. The VEN-HMA group achieved a significantly higher rate of complete remission (82.7%) compared to the cohort treated with the HAG regimen (21.7%) (P < 0.001). At the same time, the VEN-HMA group exhibited a significant survival advantage compared to the HAG treatment group(HR = 0.328, 95%CI: 0.158-0.683, P = 0.003).In patients with relapsed and refractory acute myeloid leukaemia, 43.8% of patients in the VEN-HMA treatment group achieved complete remission, which was similar to the 50% in the HAG treatment group (P > 0.99). The median overall survival was similar between the VEN-HMA and HAG groups, with 4 and 3.67 months, respectively (P = 0.290). CONCLUSIONS: In conclusion, our analyses indicated that VEN-HMA resulted in better therapeutic outcomes compared to HAG for newly diagnosed AML patients, with higher rates of complete remission and overall survival. In relapsed/refractory AML patients, there was no significant difference in the efficacy of the two treatments and further studies with larger sample sizes are warranted.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Bridged Bicyclo Compounds, Heterocyclic , Leukemia, Myeloid, Acute , Sulfonamides , Humans , Sulfonamides/therapeutic use , Sulfonamides/administration & dosage , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/mortality , Bridged Bicyclo Compounds, Heterocyclic/therapeutic use , Male , Aged , Female , Middle Aged , Retrospective Studies , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Aged, 80 and over , Adult , Treatment Outcome , Azacitidine/therapeutic use , Azacitidine/administration & dosage
2.
J Colloid Interface Sci ; 668: 492-501, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-38691959

ABSTRACT

The improvement of surface reactivity in noble-metal-free cocatalysts is crucial for the development of efficient and cost-effective photocatalytic systems. However, the influence of crystallinity on catalytic efficacy has received limited attention. Herein, we report the utilization of structurally disordered MoSe2 with abundant 1T phase as a versatile cocatalyst for photocatalytic hydrogen evolution. Using MoSe2/carbon nitride (CN) hybrids as a case study, it is demonstrated that amorphous MoSe2 significantly enhances the hydrogen evolution rate of CN, achieving up to 11.37 µmol h-1, surpassing both low crystallinity (8.24 µmol h-1) and high crystallinity MoSe2 (3.86 µmol h-1). Experimental analysis indicates that the disordered structure of amorphous MoSe2, characterized by coordination-unsaturated surface sites and a rich 1T phase with abundant active sites at the basal plane, predominantly facilitates the conversion of surface-bound protons to hydrogen. Conversely, the heightened charge transfer capacity of the highly crystalline counterpart plays a minor role in enhancing practical catalytic performance. This approach is applicable for enhancing the photocatalytic hydrogen evolution performance of various semiconducting photocatalysts, including CdS, TiO2, and ZnIn2S4, thereby offering novel insights into the advancement of high-performance non-precious catalysts through phase engineering.

3.
Syst Rev ; 13(1): 101, 2024 Apr 04.
Article in English | MEDLINE | ID: mdl-38576005

ABSTRACT

BACKGROUND AND OBJECTIVE: Immunosuppressive therapy (IST) is the first choice for severe aplastic anemia (SAA) patients with hematopoietic stem cell transplantation (HSCT) limitation, and the main factor limiting its efficacy is too few residual hematopoietic stem/progenitor cells (HSPC). Eltrombopag (EPAG), as a small molecule thrombopoietin receptor agonist, can stimulate the proliferation of residual HSPC and restore the bone marrow hematopoietic function of patients. In recent years, many studies have observed the efficacy and safety of IST combined with EPAG in the treatment of SAA, but the results are still controversial. The aim of this study is to systematically evaluate the efficacy and safety of IST combined with or without EPGA in the treatment of SAA. METHODS: We conducted a systematic review of all relevant literature published up to January 19, 2024. Pooled odds ratio (OR) was calculated to compare the rates, along with 95% confidence intervals (CI) and p value to assess whether the results were statistically significant by Review Manager 5.4.1. The p values for the interactions between each subgroup were calculated by Stata 15.1. The Newcastle-Ottawa Scale and the Cochrane bias risk assessment tools were respectively used to evaluate the quality of the literature with cohort studies and randomized controlled trials. The Review Manager 5.4.1 and Stata 15.1 were used to assess bias risk and perform the meta-analysis. RESULTS: A total of 16 studies involving 2148 patients were included. The IST combined with the EPAG group had higher overall response rate (ORR) than the IST group at 3 months (pooled OR = 2.10, 95% CI 1.58-2.79, p < 0.00001) and 6 months (pooled OR = 2.13, 95% CI 1.60-2.83, p < 0.00001), but the difference between the two groups became statistically insignificant at 12 months (pooled OR = 1.13, 95% CI 0.75-1.72, p = 0.55). The results of complete response rate (CRR) (pooled OR at 3 months = 2.73, 95% CI 1.83-4.09, p < 0.00001, 6 months = 2.76, 95% CI 2.08-3.67, p < 0.00001 and 12 months = 1.38, 95% CI 0.85-2.23, p = 0.19) were similar to ORR. Compared with the IST group, the IST combined with the EPAG group had better overall survival rate (OSR) (pooled OR = 1.70, 95% CI 1.15-2.51, p = 0.008), but there were no statistically significant differences in event-free survival rate (EFSR) (pooled OR = 1.40, 95% CI 0.93-2.13, p = 0.11), clonal evolution rate (pooled OR = 0.68, 95% CI 0.46-1.00, p = 0.05) and other adverse events between the two groups. The results of subgroup analysis showed that different ages were a source of heterogeneity, but different study types and different follow-up times were not. Moreover, all p-values for the interactions were greater than 0.05, suggesting that the treatment effect was not influenced by subgroup characteristics. CONCLUSION: EPAG added to IST enables patients to achieve earlier and faster hematologic responses with a higher rate of complete response. Although it had no effect on overall EFSR, it improved OSR and did not increase the incidence of clonal evolution and other adverse events.


Subject(s)
Anemia, Aplastic , Hydrazines , Immunosuppressive Agents , Pyrazoles , Humans , Immunosuppressive Agents/therapeutic use , Anemia, Aplastic/drug therapy , Anemia, Aplastic/epidemiology , Immunosuppression Therapy , Benzoates/therapeutic use , Pathologic Complete Response , Treatment Outcome
4.
Adv Sci (Weinh) ; 11(25): e2401345, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38647436

ABSTRACT

The development of semiconducting polymers with good processability in green solvents and competitive electrical performance is essential for realizing sustainable large-scale manufacturing and commercialization of organic electronics. A major obstacle is the processability-performance dichotomy that is dictated by the lack of ideal building blocks with balanced polarity, solubility, electronic structures, and molecular conformation. Herein, through the integration of donor, quinoid and acceptor units, an unprecedented building block, namely TQBT, is introduced for constructing a serial of conjugated polymers. The TQBT, distinct in non-symmetric structure and high dipole moment, imparts enhanced solubility in anisole-a green solvent-to the polymer TQBT-T. Furthermore, PTQBT-T possess a highly rigid and planar backbone owing to the nearly coplanar geometry and quinoidal nature of TQBT, resulting in strong aggregation in solution and localized aggregates in film. Remarkably, PTQBT-T films spuncast from anisole exhibit a hole mobility of 2.30 cm2 V-1 s-1, which is record high for green solvent-processable semiconducting polymers via spin-coating, together with commendable operational and storage stability. The hybrid building block emerges as a pioneering electroactive unit, shedding light on future design strategies in high-performance semiconducting polymers compatible with green processing and marking a significant stride towards ecofriendly organic electronics.

5.
Medicine (Baltimore) ; 103(5): e36951, 2024 Feb 02.
Article in English | MEDLINE | ID: mdl-38306571

ABSTRACT

RATIONALE: Nonsecretory multiple myeloma (NSMM) is a rare subtype of multiple myelom, occurring in 1% to 2% of multiple myelom and characterized by the inability of clonal plasma cells to synthesize or secrete immunoglobulins. We describe a 71-year-old male patient who began with bone pain and was referred to hospital several times, but was not properly diagnosed and effectively treated. PATIENT CONCERNS: A 71-year-old male patient visited our hematology department, complaining of lumbago for 1 year and back pain for half a year. DIAGNOSES: Low-dose whole-body bone computed tomography: multiple bone destruction of the sternum, ribs, multiple vertebrae and accessories of the spine, pelvis, bilateral humerus, and proximal femur. Monoclonal plasma cells accounted for 17.5% of nuclear cells in bone marrow puncture smear. Fluorescence in situ hybridization detected amplification of CKS1B (1q21) gene. Immunofixation electrophoresis negative. About 10.72% of monoclonal plasma cells were detected by flow cytometry. Finally, he was diagnosed with NSMM. INTERVENTIONS: The patients received VCD chemotherapy (bortezomib 1.3 mg/m2, d1, d4, d8, d11; cyclophosphamide 300 mg/m2, d1-2, d8-9; dexamethasone sodium phosphate 20 mg, d1-2, d4-5, d8-9, d11-12, once every 21 days). OUTCOMES: After 2 cycles of VCD treatment, the symptoms of bone pain were significantly relieved, and the efficacy was evaluated as partial response. Follow-up chemotherapy will continue to be completed on schedule. We will continue to follow up to further evaluate the overall survival and progression-free survival. LESSONS: This case shows that NSMM is easily missed or misdiagnosed.


Subject(s)
Multiple Myeloma , Male , Humans , Aged , Multiple Myeloma/complications , Multiple Myeloma/diagnosis , Multiple Myeloma/drug therapy , In Situ Hybridization, Fluorescence , Cyclophosphamide/therapeutic use , Spine , Back Pain , Bortezomib/therapeutic use , Dexamethasone/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use
6.
Mater Horiz ; 11(1): 283-296, 2024 Jan 02.
Article in English | MEDLINE | ID: mdl-37943155

ABSTRACT

Enhancing the solution-processability of conjugated polymers (CPs) without diminishing their thin-film crystallinity is crucial for optimizing charge transport in organic field-effect transistors (OFETs). However, this presents a classic "Goldilocks zone" dilemma, as conventional solubility-tuning methods for CPs typically yield an inverse correlation between solubility and crystallinity. To address this fundamental issue, a straightforward skeletal randomization strategy is implemented to construct a quinoid-donor conjugated polymer, PA4T-Ra, that contains para-azaquinodimethane (p-AQM) and oligothiophenes as repeat units. A systematic study is conducted to contrast its properties against polymer homologues constructed following conventional solubility-tuning strategies. An unusually concurrent improvement of solubility and crystallinity is realized in the random polymer PA4T-Ra, which shows moderate polymer chain aggregation, the highest crystallinity and the least lattice disorder. Consequently, PA4T-Ra-based OFETs, fabricated under ambient air conditions, deliver an excellent hole mobility of 3.11 cm2 V-1 s-1, which is about 30 times higher than that of the other homologues and ranks among the highest for quinoidal CPs. These findings debunk the prevalent assumption that a random polymer backbone sequence results in decreased crystallinity. The considerable advantages of the skeletal randomization strategy illuminate new possibilities for the control of polymer aggregation and future design of high-performance CPs, potentially accelerating the development and commercialization of organic electronics.

7.
Hematology ; 28(1): 2249217, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37610069

ABSTRACT

BACKGROUND: Multiple myeloma (MM) is a highly heterogeneous disease. Cuproptosis is a novel mode of death that is closely associated with several diseases, such as hepatocellular carcinoma. However, its role in MM is unknown. METHODS: MM transcriptomic and clinical data were obtained from UCSC Xena and gene expression omnibus (GEO) databases. Following MM samples were divided into different subtypes based on the cuproptosis genes, the differentially expressed genes (DEGs) among different subtypes, namely, candidate cuproptosis related genes were analyzed by univariate Cox and least absolute shrinkage and selection operator (LASSO) regression to construct a cuproptosis-related risk model. After the independent prognostic analysis was performed, a nomogram was constructed. Finally, Functional enrichment analysis and immune infiltration analysis were performed in the high- and low-risk groups, potential therapeutic agents were then predicted. RESULTS: The 784 MM samples in UCSC Xena cohorts were divided into three different subtypes, and 4 out of 346 candidate cuproptosis related genes, namely CDKN2A, BCL3, KCNA3 and TTC14 were used to construct a risk model. Risk score was considered a reliable independent prognostic factor for MM patients. It was investigated that the pathway of cell cycle was significantly enriched in the high-risk group. In addition, immune score, ESTIMATE score and cytolytic activity were significantly different between different risk groups, as well as 13 immune cells such as memory B cells. Nine drugs were predicted in our study. CONCLUSION: A cuproptosis-related prognostic model was constructed, which may have a potential guiding role in the treatment of MM.


Subject(s)
Apoptosis , Multiple Myeloma , Humans , Cell Cycle , Databases, Factual , Multiple Myeloma/genetics , Nomograms , Prognosis , Copper
8.
Hematology ; 28(1): 2246268, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37589214

ABSTRACT

OBJECTIVES: To construct an endoplasmic reticulum stress-related prognostic risk score (RS) model to predict prognosis and perform a preliminary analysis of immune infiltration in patients with acute myeloid leukemia (AML). METHODS: The whole-genome expression data for AML and endoplasmic reticulum stress (ER stress)-related genes were downloaded from the GEO and GSEA databases, respectively. The samples were divided into death and survival groups, combined with clinical prognosis information. LASSO regression was used to construct a prognostic RS model. The Kaplan-Meier curve method was used to evaluate the association between different risk groups and actual survival prognosis information. A cox regression analysis was used to screen for independent survival prognostic clinical factors and construct a nomogram. CIBERSORT and ssGSEA was used for immune-related analysis. RESULTS: Eighteen ER-stress related genes were identified and a comprehensive network was constructed. Further, 5 CC, 8 MF, 17 BP, and 2 KEGG pathways were enriched. Ten optimal DEGs were obtained and a prognostic risk model was constructed. Compared to the low RS group, the OS values of the high RS group were significantly lower. A significant correlation between the different risk groups and the actual prognosis was demonstrated. Ten immune cells with significantly different distributions in different risk groups were screened. KEGG enrichment analysis showed that there were 5 signaling pathways in the high-risk group. CONCLUSIONS: The RS model can effectively predict the prognosis and has clinical implications for the prognosis of AML, combined with the correlation between different RS groups and the immune microenvironment.


Subject(s)
Leukemia, Myeloid, Acute , Nomograms , Humans , Prognosis , Leukemia, Myeloid, Acute/diagnosis , Leukemia, Myeloid, Acute/genetics , Risk Factors , Endoplasmic Reticulum Stress/genetics , Tumor Microenvironment
9.
Materials (Basel) ; 16(15)2023 Aug 04.
Article in English | MEDLINE | ID: mdl-37570178

ABSTRACT

There has been little research on the impact resistance of mortar-rock slope protection structures. To ensure that the mortar-rock interface has good adhesion properties under the action of impact loading, in this paper, based on fracture mechanics theory, a theoretical impact model was established for mortar-rock binary material. Dynamic fracture tests were carried out on mortar-rock interfaces using the split-Hopkinson pressure bar (SHPB) system. The Brazilian disc (CSTBD) specimen was prepared with one half in granite and the other half in mortar. The specimen used for the dynamic impact test was 48 mm in diameter and 25 mm thick. The effects caused by the change in interface inclination and interface shape on the dynamic fracture mode were discussed. The dynamic model parameters were obtained for different inclination angles and interfaces. The results show that both the interface inclination and interface shape have significant effects on the dynamic mechanical properties of the mortar-rock binary material. The fracture modes of the mortar-rock specimens can be classified into three types. When the interface inclination is 0°, the specimen shows shear damage with an interface fracture; when the interface inclination is in the range of 0-90°, the dynamic splitting strength of the mortar-rock material increases with increasing interface inclination, and the interface undergoes composite fracture; and when the interface inclination is 90°, the dynamic splitting strength of the specimen reaches its peak, and the interface undergoes tensile fracture. The mortar-rock interface damage follows the M-C criterion. The roughness of the interface shape has a large influence on the dynamic splitting strength of the specimens. The rougher the interface shape, the higher the interface cleavage strength and the higher the peak load that causes the material to damage. The results of this study can provide a reference for the design of mortar-rubble structures to meet the demand for impact resistance and have strong engineering application value.

10.
Front Immunol ; 14: 1170475, 2023.
Article in English | MEDLINE | ID: mdl-37483604

ABSTRACT

During B cell development in bone marrow, large precursor B cells (large Pre-B cells) proliferate rapidly, exit the cell cycle, and differentiate into non-proliferative (quiescent) small Pre-B cells. Dysregulation of this process may result in the failure to produce functional B cells and pose a risk of leukemic transformation. Here, we report that AT rich interacting domain 5B (ARID5B), a B cell acute lymphoblastic leukemia (B-ALL) risk gene, regulates B cell development at the Pre-B stage. In both mice and humans, we observed a significant upregulation of ARID5B expression that initiates at the Pre-B stage and is maintained throughout later stages of B cell development. In mice, deletion of Arid5b in vivo and ex vivo exhibited a significant reduction in the proportion of immature B cells but an increase in large and small Pre-B cells. Arid5b inhibition ex vivo also led to an increase in proliferation of both Pre-B cell populations. Metabolic studies in mouse and human bone marrow revealed that fatty acid uptake peaked in proliferative B cells then decreased during non-proliferative stages. We showed that Arid5b ablation enhanced fatty acid uptake and oxidation in Pre-B cells. Furthermore, decreased ARID5B expression was observed in tumor cells from B-ALL patients when compared to B cells from non-leukemic individuals. In B-ALL patients, ARID5B expression below the median was associated with decreased survival particularly in subtypes originating from Pre-B cells. Collectively, our data indicated that Arid5b regulates fatty acid metabolism and proliferation of Pre-B cells in mice, and reduced expression of ARID5B in humans is a risk factor for B cell leukemia.


Subject(s)
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma , Transcription Factors , Animals , Humans , Mice , Cell Proliferation , DNA-Binding Proteins/metabolism , Fatty Acids , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/genetics , Precursor Cells, B-Lymphoid/metabolism , Transcription Factors/metabolism
11.
Org Lett ; 25(28): 5356-5360, 2023 Jul 21.
Article in English | MEDLINE | ID: mdl-37417812

ABSTRACT

The photoinduced radical-based hydrophosphinylation suffered from substrate scope limitation due to the highly electrophilic property of the P(O) radical. Herein, we report an efficient catalytic system for the intermolecular anti-Markovnikov hydrophosphinylation of olefins using disulfide as a photocatalyst and also a hydrogen atom shuttle. This metal-free, base-free, and redox-neutral condition allowed the alkenes with diverse electronic properties to proceed with the anti-Markovnikov P-H addition efficiently. A plausible mechanism involving the HAT process between ArS• and P(O)-H was proposed.

12.
Oncotarget ; 14: 723-737, 2023 07 20.
Article in English | MEDLINE | ID: mdl-37477523

ABSTRACT

Patients with cancer cachexia have a poor prognosis and impaired quality of life. Numerous studies using preclinical models have shown that inflammatory cytokines play an important role in the development of cancer cachexia; however, no clinical trial targeting cytokines has been successful. Therefore, it is essential to identify molecular mechanisms to develop anti-cachexia therapies. Here we identified the uncharacterized transcript KIAA0930 as a candidate cachexic factor based on analyses of microarray datasets and an in vitro muscle atrophy assay. While conditioned media from pancreatic, colorectal, gastric, and tongue cancer cells caused muscle atrophy in vitro, conditioned medium from KIAA0930 knockdown cells did not. The PANC-1 orthotopic xenograft study showed that the tibialis anterior muscle weight and cross-sectional area were increased in mice bearing KIAA0930 knockdown cells compared to control mice. Interestingly, KIAA0930 knockdown did not cause consistent changes in the secretion of inflammatory cytokines/chemokines from a variety of cancer cell lines. An initial characterization experiment showed that KIAA0930 is localized in the cytosol and not secreted from cells. These data suggest that the action of KIAA0930 is independent of the expression of cytokines/chemokines and that KIAA0930 could be a novel therapeutic target for cachexia.


Subject(s)
Neoplasms , Quality of Life , Humans , Animals , Mice , Muscle, Skeletal/metabolism , Neoplasms/metabolism , Muscular Atrophy/metabolism , Cachexia/metabolism , Cytokines/metabolism , Phenotype , Chemokines/metabolism
13.
Materials (Basel) ; 16(11)2023 May 26.
Article in English | MEDLINE | ID: mdl-37297114

ABSTRACT

Phase engineering is an emerging strategy for tuning the electronic states and catalytic functions of nanomaterials. Great interest has recently been captured by phase-engineered photocatalysts, including the unconventional phase, amorphous phase, and heterophase. Phase engineering of photocatalytic materials (including semiconductors and cocatalysts) can effectively affect the light absorption range, charge separation efficiency, or surface redox reactivity, resulting in different catalytic behavior. The applications for phase-engineered photocatalysts are widely reported, for example, hydrogen evolution, oxygen evolution, CO2 reduction, and organic pollutant removal. This review will firstly provide a critical insight into the classification of phase engineering for photocatalysis. Then, the state-of-the-art development of phase engineering toward photocatalytic reactions will be presented, focusing on the synthesis and characterization methodologies for unique phase structure and the correlation between phase structure and photocatalytic performance. Finally, personal understanding of the current opportunities and challenges of phase engineering for photocatalysis will also be provided.

14.
Hematology ; 28(1): 2204617, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37191286

ABSTRACT

BACKGROUND: Paroxysmal nocturnal hemoglobinuria (PNH) clone can be detected in some patients with aplastic anemia (AA) before treatment. But the prognostic value of the presence of pre-treatment PNH clone for intensive immunosuppressive therapy (IIST) is controversial and no consensus on whether the occurrence of PNH/AA-PNH syndrome is related to pre-treatment PNH clone. OBJECTIVE: This study aims to summarize the prognostic value of the presence of pre-treatment PNH clone treated with IIST among the AA patients and to elucidate its relationship with the development of PNH / AA-PNH syndrome. METHODS: All published studies on the prognostic value of pre-treatment PNH clone among AA patients were retrieved. Pooled odds ratio (OR) was calculated to compare the rates, along with 95% confidence intervals (CI) and p value to assess whether the results were statistically significant. RESULTS: The meta-analysis consisted of 15 studies with a combined total of 1349 patients in the cohort. Pre-treatment PNH clone had a positive effect on AA patients 6-month (pooled OR = 1.49,95% Cl: 1.06-2.08, P = 0.020), 12-month (pooled OR = 3.10,95% Cl: 1.89-5.10, P = 0.000), and overall hematological response rate (pooled OR = 1.69,95% Cl: 1.07-2.68, P = 0.024) after IIST. Patients with pre-treatment PNH clone are more likely to develop PNH/AA-PNH syndrome after IIST(pooled OR = 2.78,95%Cl:1.21-6.39, P = 0.016). CONCLUSION: Patients with positive pre-treatment PNH clone had better hematological responses to IIST than negative. And, those patients are more likely to develop PNH/AA-PNH syndrome after IIST.


Subject(s)
Anemia, Aplastic , Hemoglobinuria, Paroxysmal , Humans , Anemia, Aplastic/drug therapy , Hemoglobinuria, Paroxysmal/drug therapy , Prognosis , Immunosuppression Therapy , Clone Cells , Syndrome
15.
Org Lett ; 25(9): 1600-1604, 2023 Mar 10.
Article in English | MEDLINE | ID: mdl-36853119

ABSTRACT

The photoinduced anti-Markovnikov hydroamination of olefins typically required photocatalysts with a high oxidative ability to initiate the single-electron process. Herein, we alternatively utilize bis(2,4,6-triisopropylphenyl) disulfide, an inexpensive reagent with relatively low oxidative ability, as a photo and hydrogen atom transfer catalyst to achieve intramolecular hydroamination. The mechanistic studies as well as the DFT calculations are consistent with a novel process involving N-centered radical generation through the homolysis of the in situ formed N-S species and subsequent cyclization. An array of diverse nitrogen-containing cycles could be obtained.

16.
Mol Metab ; 66: 101612, 2022 12.
Article in English | MEDLINE | ID: mdl-36243318

ABSTRACT

OBJECTIVE: Adipose tissue is the largest endocrine organ. When activated by cancer cells, adipocytes secrete adipocytokines and release fatty acids, which are then transferred to cancer cells and used for structural and biochemical support. How this metabolic symbiosis between cancer cells and adipocytes affects skeletal muscle and thermogenesis during cancer cachexia is unknown. Cancer cachexia is a multiorgan syndrome and how the communication between tissues is established has yet to be determined. We investigated adipose tissue secretory factors and explored their role in crosstalk of adipocytes, muscle, and tumor during pancreatic cancer cachexia. METHODS: We used a pancreatic cancer cachexia mouse model generated by syngenic implantation of pancreatic ductal adenocarcinoma (PDAC) cells (KPC) intraperitoneally into C57BL/6 mice and Lcn2-knockout mice. For in vitro studies, adipocytes (3T3-L1 and primary adipocytes), cachectic cancer cells (Panc0203), non-cachectic cancer cells (Du145 cells), and skeletal muscle cells (C2C12 myoblasts) were used. RESULTS: To identify molecules involved in the crosstalk of adipose tissue with muscle and tumors, we treated 3T3-L1 adipocytes with conditioned medium (CM) from cancer cells. Upon screening the secretomes from PDAC-induced adipocytes, several adipocytokines were identified, including lipocalin 2 (Lcn2). We investigated Lcn2 as a potential mediator of cachexia induced by adipocytes in response to PDAC. During tumor progression, mice exhibited a decline in body weight gain, which was accompanied by loss of adipose and muscle tissues. Tumor-harboring mice developed drastic hypothermia because of a dramatic loss of fat in brown adipose tissue (BAT) and suppression of the thermogenesis pathway. We inhibited Lcn2 with an anti-Lcn2 antibody neutralization or genomic ablation in mice. Lcn2 deficiency significantly improved body temperature in tumor-bearing mice, which was supported by the increased expression of Ucp1 and ß3-adrenergic receptor in BAT. In addition, Lcn2 inhibition abrogated the loss of fat and muscle in tumor-bearing mice. In contrast to tumor-bearing WT mice, the corresponding Lcn2-knockout mice showed reduced ATGL expression in iWAT and decreased the expression of muscle atrophy molecular markers MuRF-1 and Fbx32. CONCLUSIONS: This study showed that Lcn2 is causally involved in the dysregulation of adipose tissue-muscle-tumor crosstalk during pancreatic cancer cachexia. Therapeutic targets that suppress Lcn2 may minimize the progression of cachexia.


Subject(s)
Cachexia , Hypothermia , Lipocalin-2 , Pancreatic Neoplasms , Animals , Mice , Adipocytes/metabolism , Adipokines/metabolism , Adipose Tissue, Brown/metabolism , Cachexia/etiology , Cachexia/metabolism , Hypothermia/complications , Hypothermia/metabolism , Lipocalin-2/genetics , Lipocalin-2/metabolism , Mice, Inbred C57BL , Mice, Knockout , Muscle, Skeletal/metabolism , Pancreatic Neoplasms/complications , Pancreatic Neoplasms/metabolism , Pancreatic Neoplasms
17.
Front Psychol ; 13: 906226, 2022.
Article in English | MEDLINE | ID: mdl-35837642

ABSTRACT

Background: Psychological distress is common among infertility patients. Total scale scores are often used to represent the severity of anxiety, depression, or stress, which ignores important differences between specific symptoms, and relationships between symptoms. This study aimed to identify patterns of psychological distress experienced by infertility patients and to identify the most central symptoms of anxiety, depression, and stress. Method: From June to September 2016, 740 infertility patients were included in this cross-sectional study. Infertility patients were asked to complete the Generalized Anxiety Disorder-7, Patients Health Questionnaire-9 (PHQ-9), and Fertility Problem Inventory. Network analysis was used to examine the patterns of psychological distress in infertility patients and to test the most central symptoms of anxiety, depression, and stress. Results: Restlessness was the most central symptom in infertility patients. "Feelings of guilt" had the highest strength among PHQ-9 symptoms. "Relationship concern stress" and "sexual concern stress" had the strongest connections in the network. Stability estimation indicated that the order of node strength centrality was more stable than the order of closeness and betweenness (the CS-coefficients were 0.75, 0.13, and 0.67, respectively). In addition, network structure and global strength were invariant across gender. Limitations: The cross-sectional design did not permit identification of causal relationships. Patients in this study were recruited from one reproductive hospital; especially, most patients had low socioeconomic status, which limits generalizability of the findings. Conclusion: This study reinforces the need to better understand the underlying causes of psychological distress in infertile patients. A more detailed investigation of the relationship between these symptoms could provide information for psychosocial interventions aimed beyond "alleviating psychological distress." We should consider the individual psychological symptom pattern and its potential causes in infertility patients instead of assuming a consistent psychological distress structure.

18.
Mitochondrial DNA B Resour ; 7(6): 1084-1086, 2022.
Article in English | MEDLINE | ID: mdl-35756454

ABSTRACT

Chlorophanus auripes Faust, 1897 is a large size weevil dwell in biotopes on Salix spp. or Populus spp., which can be found common in Northern China. The complete mitogenome of C. auripes was reported in the present study. The mitogenome contains 18,149 base pairs. The composition of mitogenome is 39.4% for A, 10.1% for G, 36.0% for T and 14.5% for C. A set of 37 genes, including 13 protein-coding genes (PCGs), 22 tRNA genes, 2 rRNA genes and one control region, were annotated. There is a 1037 bps gap between Ile tRNA gene and Gln tRNA gene. The phylogenetic result supports the monophyly of Curculionidae, revealed that C. auripes was a sister group to the Pachyrhinus yasumatsui, which also belongs to the subfamily Entiminae.

19.
Sci Rep ; 12(1): 1525, 2022 01 27.
Article in English | MEDLINE | ID: mdl-35087137

ABSTRACT

Glioma is the most common and fatal primary brain tumor in humans. Myosin binding protein H (MYBPH), which was first identified as an important myofibrillar constituent of vertebrate skeletal and cardiac muscles, reduces cell motility and metastasis. However, its role in gliomas remains unclear. We evaluated the expression of MYBPH in glioma using Gene Expression Profiling Interactive Analysis ( http://gepia.cancer-pku.cn/ ) and Chinese Glioma Genome Atlas ( https://www.cgga.org.cn/ ). The results showed that MYBPH was highly expressed in glioma tissues. Moreover, MYBPH expression was significantly associated with high tumor aggressiveness and poor outcomes in glioma patients. Mechanistically, the results suggested that MYBPH might promote tumor progression by improving tumor invasion and migration. Our results establish MYBPH as an important prognostic biomarker that could be considered a potential epigenetic and immunotherapeutic target for treatment. We showed that MYBPH is a novel biomarker that is variably expressed in glioblastoma (GBM). The association of high MYBPH expression with poor prognosis in newly diagnosed GBM patients and increased expression in recurrent GBM is indicative of its role in tumor aggressiveness.


Subject(s)
Glioma , Neoplasm Recurrence, Local
20.
J Affect Disord ; 300: 137-144, 2022 03 01.
Article in English | MEDLINE | ID: mdl-34965399

ABSTRACT

BACKGROUND: Studies have evidenced the close relationships between movement behavior [physical activity (PA), sedentary behavior (SB), and sleep duration)] and anxiety. Capturing 24 h of these maternal movement behaviors during pregnancy is necessary to understand their relationships. METHODS: In a cross-sectional study design, a total of 946 prenatal women filled Pregnancy Physical Activity Questionnaire-Chinese version, Pregnancy-Related Anxiety Questionnaire, and 7-item Generalised Anxiety Disorders scale between May 2020 and April 2021. An Isotemporal Substitution Model was used to estimate the per-hour effects of replacing one behavior. RESULTS: Replacing moderate-to-vigorous PA(MVPA), light PA (LPA), or SB with sleep could reduce both general and pregnancy-specific anxiety (LPA, B = -0.61∼-0.37, P ≤ 0.01; MVPA, B = -0.35, P = 0.03; SB, B = -0.45∼-0.34, P ≤ 0.01). Replacing SB with MVPA could reduce pregnancy-specific anxiety in the group without adequate sleep duration (SB, B = -0.62,95%CI = -1.13∼-0.17). As for the types of PA, replacing household, occupational or inactivity PA with transportation PA or sleep duration reduced general anxiety (household PA: B = -0.51, 95%CI = -0.73∼-0.29, P < 0.001; occupational PA: B = -0.48, 95%CI = -0.69∼-0.27, P < 0.001; inactivity: B = -0.45, 95%CI = -0.68∼-0.24, P < 0.001). Replacing household PA, occupational PA, or inactivity with transport PA was associated with improved general anxiety (household: B = -0.33, 95%CI = -0.64∼-0.03, P = 0.29; occupational PA: B = -0.31, 95%CI = -0.62∼-0.003, P = 0.35; inactivity: B = -0.28, 95%CI = -0.56∼-0.01, P = 0.33). LIMITATIONS: A cross-sectional study design and self-reported measurement limits the reliability of study. CONCLUSION: Longer time spent in sleep and MVPA may mitigate the negative effects of SB on anxiety.


Subject(s)
Accelerometry , Sedentary Behavior , Anxiety , Cross-Sectional Studies , Exercise , Female , Humans , Pregnancy , Reproducibility of Results , Sleep
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