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1.
Proc Natl Acad Sci U S A ; 121(27): e2407570121, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38941275

RESUMO

Although mechanically interlocked molecules (MIMs) display unique properties and functions associated with their intricate connectivity, limited assembly strategies are available for their synthesis. Herein, we presented a synergistic assembly strategy based on coordination and noncovalent interactions (π-π stacking and CH⋯π interactions) to selectively synthesize molecular closed three-link chains ([Formula: see text] links), highly entangled figure-eight knots ([Formula: see text] knots), trefoil knot ([Formula: see text] knot), and Borromean ring ([Formula: see text] link). [Formula: see text] links can be created by the strategic assembly of nonlinear multicurved ligands incorporating a furan or phenyl group with the long binuclear half-sandwich organometallic Cp*RhIII (Cp* = η5-pentamethylcyclopentadienyl) clip. However, utilizing much shorter binuclear Cp*RhIII units for union with the 2,6-naphthyl-containing ligand led to a [Formula: see text] knot because of the increased π-π stacking interactions between four consecutive stacked layers and CH⋯π interactions. Weakening such π-π stacking interactions resulted in a [Formula: see text] knot. The universality of this synergistic assembly strategy for building [Formula: see text] knots was verified by utilizing a 1,5-naphthyl-containing ligand. Quantitative conversion between the [Formula: see text] knot and the simple macrocycle species was accomplished by adjusting the concentrations monitored by NMR spectroscopy and electrospray ionization mass spectrometry (ESI-MS). Furthermore, increasing the stiff π-conjugated area of the binuclear unit afforded molecular Borromean ring, and this topology is a topological isomer of the [Formula: see text] link. These artificial metalla-links and metalla-knots were confirmed by single-crystal X-ray diffraction, NMR and ESI-MS. The results offer a potent strategy for building higher-order MIMs and emphasize the critical role that noncovalent interactions play in creating sophisticated topologies.

2.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(1): 225-230, 2024 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-38387926

RESUMO

OBJECTIVE: To study the serological characteristics of ABO*A2.08 subtype and explore its genetic molecular mechanism. METHODS: ABO blood group identification was performed on proband and her family members by routine serological methods. ABO genotyping and sequence analysis were performed by polymerase chain reaction-sequence specific primer (PCR-SSP), and direct sequencing of PCR products from exons 6 and 7 of ABO gene were directly sequenced and analyzed. The effect of gene mutation in A2.08 subtype on structural stability of GTA protein was investigated by homologous protein conserved analysis, 3D molecular modeling and protein stability prediction. RESULTS: The proband's serological test results showed subtype Ax, and ABO genotyping confirmed that the proband's genotype was ABO*A207/08. Gene sequencing of the proband's father confirmed the characteristic variation of c.539G>C in the 7th exon of ABO gene, leading to the replacement of polypeptide chain p.Arg180Pro (R180P). 3D protein molecular modeling and analysis suggested that the number of hydrogen bonds of local amino acids in the protein structure was changed after the mutation, and protein stability prediction showed that the mutation had a great influence on the protein structure stability. CONCLUSION: The mutation of the 7th exon c.539G>C of ABO gene leads to the substitution of polypeptide chain amino acid, which affects the structural stability of GTA protein and leads to the change of enzyme activity, resulting in the A2.08 phenotype. The mutated gene can be stably inherited.


Assuntos
Peptídeos , Humanos , Recém-Nascido , Feminino , Alelos , Sequência de Bases , Genótipo , Fenótipo
3.
Bone Marrow Transplant ; 59(6): 785-794, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38424174

RESUMO

The prevalence of osteoporosis in post stem cell transplantation (SCT) is poorly defined. We performed a systematic review and meta-analysis to determine the prevalence of osteoporosis in patients with hematologic diseases who underwent SCT. PubMed, EMBASE, and Web of Science were searched (from inception to 30th April 2023) using Medical Subject Headlines to find studies that assessed the prevalence of osteoporosis among post SCT. Thirteen articles meeting the inclusion criteria were included in the analysis. The pooled prevalence rates of osteoporosis, osteopenia, and decreased bone mineral density (BMD) were determined to be 14.2% (95% CI 9.7-18.8), 36.0% (95% CI 23.8-48.2), and 47.8% (95% CI 36.6-58.9), respectively. Substantial heterogeneity was observed among the included studies (I² values ranged from 81% to 99%). Subgroup analyses revealed variations in prevalence based on gender, follow-up duration, age, region, sample size, and study quality. These findings suggest a high prevalence of osteoporosis in post-SCT patients. Given the negative impact of osteoporosis on prognosis and recipient survival, clinicians should prioritize preventive measures, early diagnosis, and effective treatments to minimize its impact.


Assuntos
Osteoporose , Humanos , Osteoporose/etiologia , Osteoporose/epidemiologia , Prevalência , Transplante de Células-Tronco/efeitos adversos , Densidade Óssea , Feminino , Masculino
4.
Zhongguo Zhong Yao Za Zhi ; 49(2): 498-508, 2024 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-38403325

RESUMO

To fully understand whether Saposhnikoviae Radix polysaccharides(SP) can be metabolized in gastric fluid and the meta-bolic behavior, this study systematically analyzed the metabolites in simulated gastric fluid of SP by high-performance liquid chromatography-ion trap time-of-flight mass spectrometry(HPLC-IT-TOF-MS) technology in combination with zebrafish immune activity evaluation. Based on the obtained accurate relative molecular mass, chromatographic retention behavior, MS fragmentation patterns, refe-rence standards, and relevant literature reports, 19 metabolites were analyzed and identified. Among them, five monosaccharides and 14 oligosaccharides were generated as metabolites. Several reducing sugars, including mannose, glucose, rhamnose, and xylose, were accurately identified in the gastric fluid metabolites. Zebrafish pharmacological evaluation results indicated that SP maintained good immune activity after gastric fluid metabolism, with the most significant increase in immune cell density observed at W3(simulated gastric fluid metabolism for 2 hours). Among the gastric fluid metabolites, M1 and M3(Hex-Hex-Man) may be most closely related to pharmacological activity and could be further studied as potential active fragments.


Assuntos
Medicamentos de Ervas Chinesas , Peixe-Zebra , Humanos , Animais , Cromatografia Líquida de Alta Pressão/métodos , Raízes de Plantas/química , Polissacarídeos/análise , Medicamentos de Ervas Chinesas/química
5.
BMC Pediatr ; 24(1): 67, 2024 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-38245687

RESUMO

BACKGROUND: Neonatal sepsis, a perilous medical situation, is typified by the malfunction of organs and serves as the primary reason for neonatal mortality. Nevertheless, the mechanisms underlying newborn sepsis remain ambiguous. Programmed cell death (PCD) has a connection with numerous infectious illnesses and holds a significant function in newborn sepsis, potentially serving as a marker for diagnosing the condition. METHODS: From the GEO public repository, we selected two groups, which we referred to as the training and validation sets, for our analysis of neonatal sepsis. We obtained PCD-related genes from 12 different patterns, including databases and published literature. We first obtained differential expressed genes (DEGs) for neonatal sepsis and controls. Three advanced machine learning techniques, namely LASSO, SVM-RFE, and RF, were employed to identify potential genes connected to PCD. To further validate the results, PPI networks were constructed, artificial neural networks and consensus clustering were used. Subsequently, a neonatal sepsis diagnostic prediction model was developed and evaluated. We conducted an analysis of immune cell infiltration to examine immune cell dysregulation in neonatal sepsis, and we established a ceRNA network based on the identified marker genes. RESULTS: Within the context of neonatal sepsis, a total of 49 genes exhibited an intersection between the differentially expressed genes (DEGs) and those associated with programmed cell death (PCD). Utilizing three distinct machine learning techniques, six genes were identified as common to both DEGs and PCD-associated genes. A diagnostic model was subsequently constructed by integrating differential expression profiles, and subsequently validated by conducting artificial neural networks and consensus clustering. Receiver operating characteristic (ROC) curves were employed to assess the diagnostic merit of the model, which yielded promising results. The immune infiltration analysis revealed notable disparities in patients diagnosed with neonatal sepsis. Furthermore, based on the identified marker genes, the ceRNA network revealed an intricate regulatory interplay. CONCLUSION: In our investigation, we methodically identified six marker genes (AP3B2, STAT3, TSPO, S100A9, GNS, and CX3CR1). An effective diagnostic prediction model emerged from an exhaustive analysis within the training group (AUC 0.930, 95%CI 0.887-0.965) and the validation group (AUC 0.977, 95%CI 0.935-1.000).


Assuntos
Sepse Neonatal , Recém-Nascido , Humanos , Sepse Neonatal/diagnóstico , Sepse Neonatal/genética , Apoptose , Biologia Computacional , Bases de Dados Factuais , Aprendizado de Máquina , Receptores de GABA
6.
Acta Pharmacol Sin ; 45(2): 312-326, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37833535

RESUMO

Apoptosis plays a critical role in the development of heart failure, and sphingosylphosphorylcholine (SPC) is a bioactive sphingolipid naturally occurring in blood plasma. Some studies have shown that SPC inhibits hypoxia-induced apoptosis in myofibroblasts, the crucial non-muscle cells in the heart. Calmodulin (CaM) is a known SPC receptor. In this study we investigated the role of CaM in cardiomyocyte apoptosis in heart failure and the associated signaling pathways. Pressure overload was induced in mice by trans-aortic constriction (TAC) surgery. TAC mice were administered SPC (10 µM·kg-1·d-1) for 4 weeks post-surgery. We showed that SPC administration significantly improved survival rate and cardiac hypertrophy, and inhibited cardiac fibrosis in TAC mice. In neonatal mouse cardiomyocytes, treatment with SPC (10 µM) significantly inhibited Ang II-induced cardiomyocyte hypertrophy, fibroblast-to-myofibroblast transition and cell apoptosis accompanied by reduced Bax and phosphorylation levels of CaM, JNK and p38, as well as upregulated Bcl-2, a cardiomyocyte-protective protein. Thapsigargin (TG) could enhance CaM functions by increasing Ca2+ levels in cytoplasm. TG (3 µM) annulled the protective effect of SPC against Ang II-induced cardiomyocyte apoptosis. Furthermore, we demonstrated that SPC-mediated inhibition of cardiomyocyte apoptosis involved the regulation of p38 and JNK phosphorylation, which was downstream of CaM. These results offer new evidence for SPC regulation of cardiomyocyte apoptosis, potentially providing a new therapeutic target for cardiac remodeling following stress overload.


Assuntos
Calmodulina , Insuficiência Cardíaca , Fosforilcolina/análogos & derivados , Esfingosina/análogos & derivados , Camundongos , Animais , Calmodulina/metabolismo , Calmodulina/farmacologia , Calmodulina/uso terapêutico , Cardiomegalia/tratamento farmacológico , Cardiomegalia/metabolismo , Insuficiência Cardíaca/metabolismo , Miócitos Cardíacos , Transdução de Sinais , Remodelação Ventricular , Camundongos Endogâmicos C57BL
7.
Natl Sci Rev ; 10(10): nwad187, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38059062

RESUMO

Aziridines derived from bioactive molecules may have unique pharmacological activities, making them useful in pharmacology (e.g. mitomycin C). Furthermore, the substitution of the epoxide moiety in epothilone B with aziridine, an analog of epoxides, yielded a pronounced enhancement in its anticancer efficacy. Thus, there is interest in developing novel synthetic technologies to produce aziridines from bioactive molecules. However, known methods usually require metal catalysts, stoichiometric oxidants and/or pre-functionalized amination reagents, causing difficulty in application. A practical approach without a metal catalyst and extra-oxidant for the aziridination of bioactive molecules is in demand, yet challenging. Herein, we report an electro-oxidative flow protocol that accomplishes an oxidant-free aziridination of natural products. This process is achieved by an oxidative sulfonamide/alkene cross-coupling, in which sulfonamide and alkene undergo simultaneous oxidation or alkene is oxidized preferentially. Further anticancer treatments in cell lines have demonstrated the pharmacological activities of these aziridines, supporting the potential of this method for drug discovery.

8.
Prev Med Rep ; 36: 102520, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38116281

RESUMO

This study aimed to understand the prevalence of hyperuricemia and MetS in the United States and evaluate the potential effect of gender and ethnicity on hyperuricemia and MetS. Data was obtained from National Health and Nutrition Examination Survey (NHANES) between 2011 and 2018. Logistic regression analysis was utilized to investigate the association between hyperuricemia and MetS. A total of 7273 participants with an average age of 47.59 ± 16.92 years old were enrolled in our analysis. Of all the people, 1833 were diagnosed with MetS, with which 547 (29.8 %) were found with hyperuricemia. As for gender, 261 (28.3 %) females were with both Mets and hyperuricemia and this number came to 286 (31.4 %) for males.For population distribution, Non-Hispanic American white, and Hispanic American making up 61.2 % of the cohort. The logistic regression analysis showed that there was a significant association between MetS and hyperuricemia (OR = 2.608, 95 %CI: 2.281-2.982). And the relationship still existed between both males (OR = 2.172, 95 %CI: 1.829-2.579) and females (OR = 3.464, 95 %CI: 2.868-4.185); in addition, participant's ethnicity was also found to play an important role. And the association was found either in Hispanic Americans Non-Hispanic Americans White and black or from other races. In conclusion, our study found a significant association between hyperuricemia and MetS. The higher the uric acid level, the greater risk of people getting MetS and this risk was not influenced by people's gender and ethnicity.

9.
Fa Yi Xue Za Zhi ; 39(5): 487-492, 2023 Oct 25.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-38006269

RESUMO

As an important anthropometric characteristic, human height not only contributes to the recognition of other anthropological characteristics and genetic risk factors, but also is an important part of forensic DNA phenotyping studies. Accurate estimation of height can provide more complete information about the phenotype of suspects and provide help to solve cases. In recent years, having benefited from the rapid development of molecular biological techniques and bioinformatics, height-related genetics research has made some progress. This paper describes the research progress of human height estimation from the genetic variation and the epigenetic inheritance perspectives and looks into the future research direction.


Assuntos
DNA , Biologia Molecular , Humanos , Fenótipo , DNA/genética , Genética Forense/métodos
10.
Mol Biol Evol ; 40(10)2023 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-37794645

RESUMO

Pangolins form a group of scaly mammals that are trafficked at record numbers for their meat and purported medicinal properties. Despite their conservation concern, knowledge of their evolution is limited by a paucity of genomic data. We aim to produce exhaustive genomic resources that include 3,238 orthologous genes and whole-genome polymorphisms to assess the evolution of all eight extant pangolin species. Robust orthologous gene-based phylogenies recovered the monophyly of the three genera and highlighted the existence of an undescribed species closely related to Southeast Asian pangolins. Signatures of middle Miocene admixture between an extinct, possibly European, lineage and the ancestor of Southeast Asian pangolins, provide new insights into the early evolutionary history of the group. Demographic trajectories and genome-wide heterozygosity estimates revealed contrasts between continental versus island populations and species lineages, suggesting that conservation planning should consider intraspecific patterns. With the expected loss of genomic diversity from recent, extensive trafficking not yet realized in pangolins, we recommend that populations be genetically surveyed to anticipate any deleterious impact of the illegal trade. Finally, we produce a complete set of genomic resources that will be integral for future conservation management and forensic endeavors for pangolins, including tracing their illegal trade. These comprise the completion of whole-genomes for pangolins through the hybrid assembly of the first reference genome for the giant pangolin (Smutsia gigantea) and new draft genomes (∼43x-77x) for four additional species, as well as a database of orthologous genes with over 3.4 million polymorphic sites.


Assuntos
Mamíferos , Pangolins , Animais , Pangolins/genética , Mamíferos/genética , Genoma , Filogenia , Genômica
11.
Nat Commun ; 14(1): 5355, 2023 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-37660063

RESUMO

Immunogenic programmed cell death, such as pyroptosis and ferroptosis, efficiently induces an acute inflammatory response and boosts antitumor immunity. However, the exploration of dual-inducers, particularly nonmetallic inducers, capable of triggering both pyroptosis and ferroptosis remains limited. Here we show the construction of a covalent organic framework (COF-919) from planar and twisted AIEgen-based motifs as a dual-inducer of pyroptosis and ferroptosis for efficient antitumor immunity. Mechanistic studies reveal that COF-919 displays stronger near-infrared light absorption, lower band energy, and longer lifetime to favor the generation of reactive oxygen species (ROS) and photothermal conversion, triggering pyroptosis. Because of its good ROS production capability, it upregulates intracellular lipid peroxidation, leading to glutathione depletion, low expression of glutathione peroxidase 4, and induction of ferroptosis. Additionally, the induction of pyroptosis and ferroptosis by COF-919 effectively inhibits tumor metastasis and recurrence, resulting in over 90% tumor growth inhibition and cure rates exceeding 80%.


Assuntos
Ferroptose , Estruturas Metalorgânicas , Neoplasias , Piroptose , Espécies Reativas de Oxigênio , Imunoterapia , Neoplasias/terapia
12.
Genes (Basel) ; 14(9)2023 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-37761818

RESUMO

With the emergence of high-throughput sequencing technology, a number of non-avian reptile species have been sequenced at the genome scale, shedding light on various scientific inquiries related to reptile ecology and evolution. However, the routine requirement of tissue or blood samples for genome sequencing often poses challenges in many elusive reptiles, hence limiting the application of high-throughput sequencing technologies to reptile studies. An alternative reptilian DNA resource suitable for genome sequencing is in urgent need. Here, we used the corn snake (Pantherophis guttatus) as a reptile model species to demonstrate that the shed skin is a high-quality DNA source for genome sequencing. Skin sheds provide a noninvasive type of sample that can be easily collected without restraining or harming the animal. Our findings suggest that shed skin from corn snakes yields DNA of sufficient quantity and quality that are comparable to tissue DNA extracts. Genome sequencing data analysis revealed that shed skin DNA is subject to bacteria contamination at variable levels, which is a major issue related to shed skin DNA and may be addressed by a modified DNA extraction method through introduction of a 30 min pre-digestion step. This study provides an enhanced method for the use of reptile shed skins as a high-quality DNA source for whole genome sequencing. Utilizing shed skin DNA enables researchers to overcome the limitations generally associated with obtaining traditional tissue or blood samples and promises to facilitate the application of genome sequencing in reptilian research.


Assuntos
Genoma , Répteis , Animais , Répteis/genética , Mapeamento Cromossômico , Genoma/genética , Sequência de Bases , DNA/genética
13.
Proc Natl Acad Sci U S A ; 120(40): e2304096120, 2023 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-37748052

RESUMO

Eight extant species of pangolins are currently recognized. Recent studies found that two mitochondrial haplotypes identified in confiscations in Hong Kong could not be assigned to any known pangolin species, implying the existence of a species. Here, we report that two additional mitochondrial haplotypes identified in independent confiscations from Yunnan align with the putative species haplotypes supporting the existence of this mysterious species/population. To verify the new species scenario we performed a comprehensive analysis of scale characteristics and 138 whole genomes representing all recognized pangolin species and the cryptic new species, 98 of which were generated here. Our morphometric results clearly attributed this cryptic species to Asian pangolins (Manis sp.) and the genomic data provide robust and compelling evidence that it is a pangolin species distinct from those recognized previously, which separated from the Philippine pangolin and Malayan pangolin over 5 Mya. Our study provides a solid genomic basis for its formal recognition as the ninth pangolin species or the fifth Asian one, supporting a new taxonomic classification of pangolins. The effects of glacial climate changes and recent anthropogenic activities driven by illegal trade are inferred to have caused its population decline with the genomic signatures showing low genetic diversity, a high level of inbreeding, and high genetic load. Our finding greatly expands current knowledge of pangolin diversity and evolution and has vital implications for conservation efforts to prevent the extinction of this enigmatic and endangered species from the wild.


Assuntos
Genômica , Pangolins , Animais , Efeitos Antropogênicos , Ásia , China , Pangolins/genética , Crescimento Demográfico
14.
Zhongguo Dang Dai Er Ke Za Zhi ; 25(7): 711-717, 2023 Jul 15.
Artigo em Chinês | MEDLINE | ID: mdl-37529953

RESUMO

OBJECTIVES: To investigate the physical growth and dietary characteristics of children with attention deficit hyperactivity disorder (ADHD), and to analyze their relationship with core symptoms of ADHD. METHODS: A total of 268 children who were newly diagnosed with ADHD in Children's Hospital of Nanjing Medical University from June to December 2020 were included in the ADHD group, and 102 healthy children who underwent physical examination during the same period were selected as the control group. Physical evaluations and dietary surveys were conducted for both groups. ADHD diagnosis and scoring were performed according to the Diagnostic and Statistical Manual of Mental Disorders (5th edition). Factor analysis, Spearman correlation analysis, and mediation analysis were used to study the relationship between core symptoms of ADHD, dietary patterns, and physical growth. RESULTS: The rate of overweight/obesity in the ADHD group was significantly higher than that in the control group (35.8% vs 21.6%, P<0.05). Three dietary patterns were extracted from the food frequency questionnaire: vegetarian dietary pattern, traditional dietary pattern, and snack/fast food pattern. The factor score for the snack/fast food pattern in the ADHD group was higher than that in the control group (P<0.05). There was a significant positive correlation between ADHD symptom scores, snack/fast food pattern factor scores, and body fat percentage (P<0.05). The mediation analysis showed that the snack/fast food pattern played a partial mediating role in the relationship between ADHD symptom scores and body fat percentage, with a mediation proportion of 26.66%. CONCLUSIONS: The rate of overweight/obesity in children with ADHD is higher than that in non-ADHD children. Core symptoms of ADHD are related to dietary patterns and physical growth, with the snack/fast food pattern playing a partial mediating role in the relationship between core symptoms of ADHD and physical growth.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Obesidade Infantil , Humanos , Criança , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Estudos Transversais , Sobrepeso , Dieta
15.
Polymers (Basel) ; 15(15)2023 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-37571182

RESUMO

The friction stir welding (FSW) of thermoplastic polymers is gradually receiving attention because of its advantages including high efficiency and pollution-free manufacturing. The extrusion-based additive manufacturing (EAM) of polymers has also become one of the main processing methods for thermoplastic parts. In this paper, a hybrid manufacturing method for the FSW process and EAM technology is proposed and explored. The effects of the FSW process using two different welding tools on the mechanical behaviors of 3D printing polymer parts were compared and investigated and the corresponding mechanism was analyzed. The results show that the appropriate welding tool is beneficial for eliminating the anisotropy and decreasing the porosity of 3D-printed parts. Therefore, the improving effects of the FSW process on the mechanical behaviors of the EAM parts are verified. The mechanism was attributed to the high-speed rotation of the welding tool with the appropriate shape, which can promote the flow of polymer melt in the welding region, leading to the formation of dense structures caused by the entanglement of the molecular chains. This study may provide some assistance in modern industrial manufacturing for the processing of large custom components.

16.
Integr Cancer Ther ; 22: 15347354231188679, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37565358

RESUMO

BACKGROUND: Aromatase inhibitors (AIs) are recommended as the preferred therapy for postmenopausal women with hormone receptor-positive (HR+) breast cancer. As a result, aromatase inhibitor-associated musculoskeletal symptom (AIMSS) have become a major problem leading to therapy discontinuation and decreased quality of life in patients receiving adjuvant AIs treatment. Multiple therapies have been attempted, but have yielded limited clinical results. This study will be performed to determine whether acupoint thread embedding (ATE) combined with Wenshen Bugu Decoction can effectively treat AIMSS, so as to improve the AIs medication compliance of postmenopausal breast cancer patients. METHODS: This study will utilize a randomized, 2 parallel groups controlled trial design. A total of 128 eligible postmenopausal breast cancer women with AIMSS will be randomized to receive a 12-week treatment with Wenshen Bugu Decoction alone (control group) or in combination with ATE (treatment group) in a 1:1 ratio. The primary outcome will be the 12 week Brief Pain Inventory Worst Pain (BPI-WP) score. The secondary outcome measures will include response rate, Brief Pain Inventory-Short Form (BFI-SF), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Functional Assessment of Cancer Therapy-Endocrine Symptom (FACT-ES), Functional Assessment of Cancer Therapy-Breast (FACT-B), bone marrow density (BMD), blood markers of bone metabolite, Morisky medication adherence scale-8 (MMAS-8), credibility and expectancy, and survival outcomes. DISCUSSION: This trial may provide clinical evidence that ATE combined with Wenshen Bugu Decoction can be beneficial for treating AIMSS among postmenopausal breast cancer survivors. Our findings will be helpful to enhance the quality of life and reduce the occurrence of AIs withdrawal.


Assuntos
Inibidores da Aromatase , Neoplasias da Mama , Humanos , Feminino , Inibidores da Aromatase/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/complicações , Qualidade de Vida , Pontos de Acupuntura , Pós-Menopausa , Dor/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto
17.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 31(4): 1113-1118, 2023 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-37551485

RESUMO

OBJECTIVE: To construct a myeloproliferative neoplasms (MPN) transplanted mouse model with JAK2-V617F, MPLW515L or CALR-Type I gene mutation, and establish a systematic evaluation system to verify the success of model construction. METHODS: The bone marrow c-kit+ cells of the mice were obtained by the following steps: The mice were killed by cervical dislocation, the femur, tibia and ilium were separated, and the bone marrow cells were collected. The c-kit+ cells were sorted after incubation with CD117 magnetic beads. The method of constructing mouse primary mutant cells is as follows: A gene mutation vector with a GFP tag was constructed by the retroviral system, and the retroviral vector was packaged into the Platinum-E cells to obtain the virus supernatant, and then used it to infect the c-kit+ cells of mice. The MPN mouse model was constructed as follows: the mouse primary c-kit+ cells containing the mutant genes were collected after infection, and then transplanted them via the tail vein into the female recipient mice of the same species which were irradiated with a lethal dose of gamma rays (8.0 Gy). The MPN mouse model was evaluated as follows: After transplantation, the peripheral blood of the mice was regularly collected from the tail vein to perform the complete blood count test, and the size of spleen and the degree of bone marrow fibrosis were estimated. RESULTS: The mouse c-kit+ cells with the mutant genes were successfully obtained from the bone marrow. MPN mouse model was successfully constructed: The peripheral blood cells of the MPN-transplanted mice carried exogenous implanted GFP-positive cells, and the white blood cells (WBC), platelet (PLT) and hematocrit (HCT) were all increased; the body weight loss, and the water and food intake were reduced in the transplanted mice; further pathological analysis showed that the transplanted mice displayed splenomegaly and bone marrow fibrosis. These results suggested that the MPN mouse model was successfully constructed. According to the common and different characteristics of the three MPN mouse model, a preliminary evaluation system for judging the success of MPN mouse model construction was summarized, which mainly included the following indicators, for example, the proportion of GFP-positive cells in the peripheral blood of mice; WBC, PLT and HCT; the degree of spleen enlargement and the bone marrow fibrosis. CONCLUSION: The MPN mouse model with JAK2-V617F, MPLW515L or CALR-Type I gene mutation is successfully established by retroviral system, which can provide an important experimental animal model for the research of MPN pathogenesis and drug-targeted therapy.


Assuntos
Transtornos Mieloproliferativos , Neoplasias , Mielofibrose Primária , Feminino , Camundongos , Animais , Transtornos Mieloproliferativos/genética , Medula Óssea/patologia , Mutação , Modelos Animais de Doenças , Janus Quinase 2/genética
18.
Nat Ecol Evol ; 7(11): 1914-1929, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37652999

RESUMO

The tiger (Panthera tigris) is a charismatic megafauna species that originated and diversified in Asia and probably experienced population contraction and expansion during the Pleistocene, resulting in low genetic diversity of modern tigers. However, little is known about patterns of genomic diversity in ancient populations. Here we generated whole-genome sequences from ancient or historical (100-10,000 yr old) specimens collected across mainland Asia, including a 10,600-yr-old Russian Far East specimen (RUSA21, 8× coverage) plus six ancient mitogenomes, 14 South China tigers (0.1-12×) and three Caspian tigers (4-8×). Admixture analysis showed that RUSA21 clustered within modern Northeast Asian phylogroups and partially derived from an extinct Late Pleistocene lineage. While some of the 8,000-10,000-yr-old Russian Far East mitogenomes are basal to all tigers, one 2,000-yr-old specimen resembles present Amur tigers. Phylogenomic analyses suggested that the Caspian tiger probably dispersed from an ancestral Northeast Asian population and experienced gene flow from southern Bengal tigers. Lastly, genome-wide monophyly supported the South China tiger as a distinct subspecies, albeit with mitochondrial paraphyly, hence resolving its longstanding taxonomic controversy. The distribution of mitochondrial haplogroups corroborated by biogeographical modelling suggested that Southwest China was a Late Pleistocene refugium for a relic basal lineage. As suitable habitat returned, admixture between divergent lineages of South China tigers took place in Eastern China, promoting the evolution of other northern subspecies. Altogether, our analysis of ancient genomes sheds light on the evolutionary history of tigers and supports the existence of nine modern subspecies.


Assuntos
Tigres , Animais , Tigres/genética , DNA Antigo , Filogenia , Federação Russa , China
19.
World J Clin Cases ; 11(19): 4531-4543, 2023 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-37469730

RESUMO

BACKGROUND: Stroke is a common cause of neurological dysfunction, often resulting in hemiplegia. Thus, rehabilitation of limb function in stroke patients is an important step towards accelerating recovery and improving quality of life. AIM: To investigate whether unilateral strength training in hemiplegic stroke patients could lead to cross-migration, an increase in bilateral muscle strength, and an improvement in lower limb motor function. METHODS: We randomly divided 120 patients with hemiplegic stroke into two groups: Eexperimental and control groups, with 60 patients in each group. Both groups received routine rehabilitation treatment, while the experimental group additionally received ankle dorsiflexion resistance training on the healthy side for 6 wk. We measured the maximum voluntary contract (MVC), changes in surface electromyography (EMG), and the lower limb motor function using the simplified Fugl Meyer Motor Function Assessment Scale (FMA) before and within 1 wk after training. RESULTS: The FMA score in the experimental group improved significantly compared to both their pre-training score and the control group's post-training score (P < 0.05). The integrated EMG of the anterior tibialis muscle and pulmonary intestine muscle in the experimental group were significantly different after training than before (P < 0.05). Furthermore, the MVC of the anterior tibialis muscle on both the healthy and affected sides and the MVC of the pulmonary intestine muscle on both sides showed significant improvement compared with before training and the control group (P < 0.05). CONCLUSION: Our findings suggest that ankle dorsiflexion resistance training on the healthy side in hemiplegic stroke patients can increase strength in the opposite tibialis anterior muscle and antagonist's muscle, indicating a cross-migration phenomenon of strength training. Furthermore, this type of training can also improve lower limb motor function, providing a new exercise method for improving early ankle dorsiflexion dysfunction.

20.
Adv Sci (Weinh) ; 10(26): e2302361, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37431193

RESUMO

Lightweight and flexible electronic materials with high energy attenuation hold an unassailable position in electromagnetic stealth and intelligent devices. Among them, emerging heterodimensional structure draws intensive attention in the frontiers of materials, chemistry, and electronics, owing to the unique electronic, magnetic, thermal, and optical properties. Herein, an intrinsic heterodimensional structure consisting of alternating assembly of 0D magnetic clusters and 2D conductive layers is developed, and its macroscopic electromagnetic properties are flexibly designed by customizing the number of oxidative molecular layer deposition (oMLD) cycles. This unique heterodimensional structure features highly ordered spatial distribution, with an achievement of electron-dipole and magnetic-dielectric double synergies, which exhibits the high attenuation of electromagnetic energy (160) and substantial improvement of dielectric loss tangent (≈200%). It can respond to electromagnetic waves of different bands to achieve multispectral stealth, covering visible light, infrared radiation, and gigahertz wave. Importantly, two kinds of ingenious information interaction devices are constructed with heterodimensional structure. The hierarchical antennas allow precise targeting of operating bands (S- to Ku- bands) by oMLD cycles. The strain imaging device with high sensitivity opens a new horizon for visual interaction. This work provides a creative insight for developing advanced micro-nano materials and intelligent devices.

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