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1.
Cell ; 186(20): 4422-4437.e21, 2023 09 28.
Article in English | MEDLINE | ID: mdl-37774680

ABSTRACT

Recent work has identified dozens of non-coding loci for Alzheimer's disease (AD) risk, but their mechanisms and AD transcriptional regulatory circuitry are poorly understood. Here, we profile epigenomic and transcriptomic landscapes of 850,000 nuclei from prefrontal cortexes of 92 individuals with and without AD to build a map of the brain regulome, including epigenomic profiles, transcriptional regulators, co-accessibility modules, and peak-to-gene links in a cell-type-specific manner. We develop methods for multimodal integration and detecting regulatory modules using peak-to-gene linking. We show AD risk loci are enriched in microglial enhancers and for specific TFs including SPI1, ELF2, and RUNX1. We detect 9,628 cell-type-specific ATAC-QTL loci, which we integrate alongside peak-to-gene links to prioritize AD variant regulatory circuits. We report differential accessibility of regulatory modules in late AD in glia and in early AD in neurons. Strikingly, late-stage AD brains show global epigenome dysregulation indicative of epigenome erosion and cell identity loss.


Subject(s)
Alzheimer Disease , Brain , Gene Expression Regulation , Humans , Alzheimer Disease/genetics , Alzheimer Disease/pathology , Brain/pathology , Epigenome , Epigenomics , Genome-Wide Association Study
2.
Brief Bioinform ; 24(3)2023 05 19.
Article in English | MEDLINE | ID: mdl-37170752

ABSTRACT

Haplotype networks are graphs used to represent evolutionary relationships between a set of taxa and are characterized by intuitiveness in analyzing genealogical relationships of closely related genomes. We here propose a novel algorithm termed McAN that considers mutation spectrum history (mutations in ancestry haplotype should be contained in descendant haplotype), node size (corresponding to sample count for a given node) and sampling time when constructing haplotype network. We show that McAN is two orders of magnitude faster than state-of-the-art algorithms without losing accuracy, making it suitable for analysis of a large number of sequences. Based on our algorithm, we developed an online web server and offline tool for haplotype network construction, community lineage determination, and interactive network visualization. We demonstrate that McAN is highly suitable for analyzing and visualizing massive genomic data and is helpful to enhance the understanding of genome evolution. Availability: Source code is written in C/C++ and available at https://github.com/Theory-Lun/McAN and https://ngdc.cncb.ac.cn/biocode/tools/BT007301 under the MIT license. Web server is available at https://ngdc.cncb.ac.cn/bit/hapnet/. SARS-CoV-2 dataset are available at https://ngdc.cncb.ac.cn/ncov/. Contact: songshh@big.ac.cn (Song S), zhaowm@big.ac.cn (Zhao W), baoym@big.ac.cn (Bao Y), zhangzhang@big.ac.cn (Zhang Z), ybxue@big.ac.cn (Xue Y).


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Haplotypes , SARS-CoV-2/genetics , COVID-19/genetics , Algorithms , Genomics , Software
3.
Nano Lett ; 24(1): 16-25, 2024 Jan 10.
Article in English | MEDLINE | ID: mdl-38109350

ABSTRACT

The anomalous Hall effect (AHE) is an important transport signature revealing topological properties of magnetic materials and their spin textures. Recently, MnBi2Te4 has been demonstrated to be an intrinsic magnetic topological insulator. However, the origin of its intriguing AHE behaviors remains elusive. Here, we demonstrate the Berry curvature-dominated intrinsic AHE in wafer-scale MnBi2Te4 films. By applying back-gate voltages, we observe an ambipolar conduction and n-p transition in ∼7-layer MnBi2Te4, where a quadratic relation between the AHE resistance and longitudinal resistance suggests its intrinsic AHE nature. In particular, for ∼3-layer MnBi2Te4, the AHE sign can be tuned from pristine negative to positive. First-principles calculations unveil that such an AHE reversal originated from the competing Berry curvature between oppositely polarized spin-minority-dominated surface states and spin-majority-dominated inner bands. Our results shed light on the underlying physical mechanism of the intrinsic AHE and provide new perspectives for the unconventional sign-tunable AHE.

4.
Biochem Biophys Res Commun ; 711: 149934, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38626621

ABSTRACT

C-terminally encoded peptides (CEPs) are peptide hormones that function as mobile signals coordinating crucial developmental programs in plants. Previous studies have revealed that CEPs exert negative regulation on root development through interaction with CEP receptors (CEPRs), CEP DOWNSTREAMs (CEPDs), the cytokinin receptor ARABIDOPSIS HISTIDINE KINASE (AHKs) and the transcriptional repressor Auxin/Indole-3-Acetic Acid (AUX/IAA). However, the precise molecular mechanisms underlying CEPs-mediated regulation of root development via auxin and cytokinin signaling pathways still necessitate further detailed investigation. In this study, we examined prior research and elucidated the underlying molecular mechanisms. The results showed that both synthetic AtCEPs and overexpression of AtCEP5 markedly supressed primary root elongation and lateral root (LR) formation in Arabidopsis. Molecular biology and genetics elucidated how CEPs inhibit root growth by suppressing auxin signaling while promoting cytokinin signaling. In summary, this study elucidated the inhibitory effects of AtCEPs on Arabidopsis root growth and provided insights into their potential molecular mechanisms, thus enhancing our comprehension of CEP-mediated regulation of plant growth and development.


Subject(s)
Arabidopsis Proteins , Arabidopsis , Cytokinins , Gene Expression Regulation, Plant , Indoleacetic Acids , Plant Roots , Signal Transduction , Arabidopsis/growth & development , Arabidopsis/metabolism , Arabidopsis/genetics , Cytokinins/metabolism , Indoleacetic Acids/metabolism , Plant Roots/growth & development , Plant Roots/metabolism , Arabidopsis Proteins/metabolism , Arabidopsis Proteins/genetics , Plant Growth Regulators/metabolism , Peptide Hormones/metabolism , Peptide Hormones/genetics
5.
Small ; : e2401966, 2024 May 11.
Article in English | MEDLINE | ID: mdl-38733223

ABSTRACT

While research on organic thermoelectric polymers is making significant progress in recent years, realization of a single polymer material possessing both thermoelectric properties and stretchability for the next generation of self-powered wearable electronics is a challenging task and remains an area yet to be explored. A new molecular engineering concept of "conjugated breaker" is employed to impart stretchability to a highly crystalline diketopyrrolepyrrole (DPP)-based polymer. A hexacyclic diindenothieno[2,3-b]thiophene (DITT) unit, with two 4-octyloxyphenyl groups substituted at the tetrahedral sp3-carbon bridges, is selected to function as the conjugated breaker that can sterically hinder intermolecular packing to reduce polymers' crystallinity. A series of donor-acceptor random copolymers is thus developed via polymerizing the crystalline DPP units with the DITT conjugated breakers. By controlling the monomeric DPP/DITT ratios, DITT30 reaches the optimal balance of crystalline/amorphous regions, exhibiting an exceptional power factor (PF) value up to 12.5 µW m-1 K-2 after FeCl3-doping; while, simultaneously displaying the capability to withstand strains exceeding 100%. More significantly, the doped DITT30 film possesses excellent mechanical endurance, retaining 80% of its initial PF value after 200 cycles of stretching/releasing at a strain of 50%. This research marks a pioneering achievement in creating intrinsically stretchable polymers with exceptional thermoelectric properties.

6.
J Transl Med ; 22(1): 81, 2024 01 20.
Article in English | MEDLINE | ID: mdl-38245788

ABSTRACT

BACKGROUND: The long-term impact of COVID-19-associated public health interventions on zoonotic and vector-borne infectious diseases (ZVBs) remains uncertain. This study sought to examine the changes in ZVBs in China during the COVID-19 pandemic and predict their future trends. METHODS: Monthly incidents of seven ZVBs (Hemorrhagic fever with renal syndrome [HFRS], Rabies, Dengue fever [DF], Human brucellosis [HB], Leptospirosis, Malaria, and Schistosomiasis) were gathered from January 2004 to July 2023. An autoregressive fractionally integrated moving average (ARFIMA) by incorporating the COVID-19-associated public health intervention variables was developed to evaluate the long-term effectiveness of interventions and forecast ZVBs epidemics from August 2023 to December 2025. RESULTS: Over the study period, there were 1,599,647 ZVBs incidents. HFRS and rabies exhibited declining trends, HB showed an upward trajectory, while the others remained relatively stable. The ARFIMA, incorporating a pulse pattern, estimated the average monthly number of changes of - 83 (95% confidence interval [CI] - 353-189) cases, - 3 (95% CI - 33-29) cases, - 468 (95% CI - 1531-597) cases, 2191 (95% CI 1056-3326) cases, 7 (95% CI - 24-38) cases, - 84 (95% CI - 222-55) cases, and - 214 (95% CI - 1036-608) cases for HFRS, rabies, DF, HB, leptospirosis, malaria, and schistosomiasis, respectively, although these changes were not statistically significant besides HB. ARFIMA predicted a decrease in HB cases between August 2023 and December 2025, while indicating a relative plateau for the others. CONCLUSIONS: China's dynamic zero COVID-19 strategy may have exerted a lasting influence on HFRS, rabies, DF, malaria, and schistosomiasis, beyond immediate consequences, but not affect HB and leptospirosis. ARFIMA emerges as a potent tool for intervention analysis, providing valuable insights into the sustained effectiveness of interventions. Consequently, the application of ARFIMA contributes to informed decision-making, the design of effective interventions, and advancements across various fields.


Subject(s)
COVID-19 , Hemorrhagic Fever with Renal Syndrome , Leptospirosis , Malaria , Rabies , Schistosomiasis , Vector Borne Diseases , Humans , Seasons , Hemorrhagic Fever with Renal Syndrome/epidemiology , Public Health , Interrupted Time Series Analysis , Pandemics , Rabies/epidemiology , Rabies/prevention & control , Incidence , COVID-19/epidemiology , Vector Borne Diseases/epidemiology , China/epidemiology , Leptospirosis/epidemiology , Schistosomiasis/epidemiology
7.
J Exp Bot ; 75(11): 3388-3400, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38497798

ABSTRACT

Nitrogen fertilizer is widely used in agriculture to boost crop yields. Plant growth-promoting rhizobacteria (PGPRs) can increase plant nitrogen use efficiency through nitrogen fixation and organic nitrogen mineralization. However, it is not known whether they can activate plant nitrogen uptake. In this study, we investigated the effects of volatile compounds (VCs) emitted by the PGPR strain Bacillus velezensis SQR9 on plant nitrogen uptake. Strain SQR9 VCs promoted nitrogen accumulation in both rice and Arabidopsis. In addition, isotope labeling experiments showed that strain SQR9 VCs promoted the absorption of nitrate and ammonium. Several key nitrogen-uptake genes were up-regulated by strain SQR9 VCs, such as AtNRT2.1 in Arabidopsis and OsNAR2.1, OsNRT2.3a, and OsAMT1 family members in rice, and the deletion of these genes compromised the promoting effect of strain SQR9 VCs on plant nitrogen absorption. Furthermore, calcium and the transcription factor NIN-LIKE PROTEIN 7 play an important role in nitrate uptake promoted by strain SQR9 VCs. Taken together, our results indicate that PGPRs can promote nitrogen uptake through regulating plant endogenous signaling and nitrogen transport pathways.


Subject(s)
Arabidopsis , Bacillus , Nitrogen , Oryza , Signal Transduction , Bacillus/metabolism , Bacillus/physiology , Bacillus/genetics , Nitrogen/metabolism , Oryza/microbiology , Oryza/metabolism , Oryza/genetics , Arabidopsis/metabolism , Arabidopsis/microbiology , Arabidopsis/genetics , Gene Expression Regulation, Plant , Volatile Organic Compounds/metabolism
8.
Org Biomol Chem ; 22(16): 3186-3197, 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38591656

ABSTRACT

This review showcases a systematic overview of the available tools for the catalytic asymmetric transformation of biaryl substrates toward the construction of challenging enantioenriched helicenes and the conceptual aspects associated with each type of transformation. Depending on the properties of the biaryl and the nature of the process, several methodologies have been developed, including olefin metathesis, hydroarylation of alkynes, C-X (X = C, O, N) coupling, and C-H functionalization. Pioneering studies and an array of representative reactions are discussed to underscore the potential of these synthetic protocols.

9.
Arch Virol ; 169(7): 134, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38834736

ABSTRACT

Anthrax is an acute infectious zoonotic disease caused by Bacillus anthracis, a bacterium that is considered a potential biological warfare agent. Bacillus bacteriophages shape the composition and evolution of bacterial communities in nature and therefore have important roles in the ecosystem community. B. anthracis phages are not only used in etiological diagnostics but also have promising prospects in clinical therapeutics or for disinfection in anthrax outbreaks. In this study, two temperate B. anthracis phages, vB_BanS_A16R1 (A16R1) and vB_BanS_A16R4 (A16R4), were isolated and showed siphovirus-like morphological characteristics. Genome sequencing showed that the genomes of phages A16R1 and A16R4 are 36,569 bp and 40,059 bp in length, respectively. A16R1 belongs to the genus Wbetavirus, while A16R4 belongs to the genus Hubeivirus and is the first phage of that genus found to lyse B. anthracis. Because these two phages can comparatively specifically lyse B. anthracis, they could be used as alternative diagnostic tools for identification of B. anthracis infections.


Subject(s)
Bacillus Phages , Bacillus anthracis , Genome, Viral , Bacillus anthracis/virology , Genome, Viral/genetics , Bacillus Phages/isolation & purification , Bacillus Phages/genetics , Bacillus Phages/classification , Siphoviridae/genetics , Siphoviridae/isolation & purification , Siphoviridae/classification , Phylogeny
10.
BMC Pulm Med ; 24(1): 201, 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38658897

ABSTRACT

PURPOSE: To summarize and analyze the safety and efficacy of a Y-shape Sigma stent loaded with I125 in patients with inoperable malignant main airway obstruction. METHODS: This study was approved by the Institutional Ethics Committee, and a written informed consent was obtained from each participant. A Y-shape Sigma stent loaded with I125 was placed under vision from rigid bronchoscopy. The primary endpoint was alleviation of symptoms and improvement of Karnofsky Performance Status (KPS) score, and the secondary endpoint was complications and technical success. RESULTS: From November 2018 through June 2023, total 33 patients with malignant airway obstruction were palliatively treated by installing Y-shape Sigma stents loaded with I125. The airway lumen was immediately restored and the average airway opening significantly increased to 70 ± 9.4% after the procedure from baseline 30.2 ± 10.5% (p < 0.05). Average KPS score was improved from baseline 30.0 ± 10.0 to 70.0 ± 10.0 (p < 0.05) as well as PaO2 from baseline 50.1 ± 15.4 mmHg to 89.3 ± 8.6 mmHg (p < 0.05). The technical success rate of placing the stent in this study was 73%, and adverse events or complications including bleeding, I125 loss, and airway infection occurred during or after the procedure. CONCLUSION: Placement of Y-shape Sigma stents under vision from rigid bronchoscopy in the patients with malignant airway obstruction is feasible and it immediately alleviates dyspnea and significantly improves quality of life.


Subject(s)
Airway Obstruction , Bronchoscopy , Iodine Radioisotopes , Palliative Care , Stents , Humans , Bronchoscopy/methods , Airway Obstruction/therapy , Male , Female , Aged , Middle Aged , Palliative Care/methods , Lung Neoplasms/complications , Karnofsky Performance Status , Aged, 80 and over , Treatment Outcome , Brachytherapy/methods , Brachytherapy/adverse effects , Adult
11.
Plant J ; 110(6): 1564-1577, 2022 06.
Article in English | MEDLINE | ID: mdl-35365951

ABSTRACT

The essential micronutrient manganese (Mn) in plants regulates multiple biological processes including photosynthesis and oxidative stress. Some Natural Resistance-Associated Macrophage Proteins (NRAMPs) have been reported to play critical roles in Mn uptake and reutilization in low Mn conditions. NRAMP6 was demonstrated to regulate cadmium tolerance and iron utilization in Arabidopsis. Nevertheless, it is unclear whether NRAMP6 plays a role in Mn nutrition. Here, we report that NRAMP6 cooperates with NRAMP1 in Mn utilization. Mutation of NRAMP6 in nramp1 but not in a wild-type background reduces root growth and Mn translocation from the roots to shoots under Mn deficient conditions. Grafting experiments revealed that NRAMP6 expression in both the roots and shoots is required for root growth and Mn translocation under Mn deficiency. We also showed that NRAMP1 could replace NRAMP6 to sustain root growth under Mn deficiency, but not vice versa. Mn deficiency does not affect the transcript level of NRAMP6, but is able to increase and decrease the protein accumulation of NRAMP6 in roots and shoots, respectively. Furthermore, NRAMP6 can be localized to both the plasma membrane and endomembranes including the endoplasmic reticulum, and Mn deficiency enhances the localization of NRAMP6 to the plasma membrane in Arabidopsis plants. NRAMP6 could rescue the defective growth of the yeast mutant Δsmf2, which is deficient in endomembrane Mn transport. Our results reveal the important role of NRAMP6 in Mn nutrition and in the long-distance signaling between the roots and shoots under Mn deficient conditions.


Subject(s)
Arabidopsis Proteins , Arabidopsis , Biological Phenomena , Arabidopsis/metabolism , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , Biological Transport , Manganese/metabolism , Plant Roots/genetics , Plant Roots/metabolism , Plants/metabolism
12.
Stroke ; 54(11): 2906-2917, 2023 11.
Article in English | MEDLINE | ID: mdl-37746705

ABSTRACT

BACKGROUND: Cerebral cavernous malformations (CCMs) are vascular malformations that frequently cause stroke. CCMs arise due to loss of function in one of the genes that encode the CCM complex, a negative regulator of MEKK3-KLF2/4 signaling in vascular endothelial cells. Gain-of-function mutations in PIK3CA (encoding the enzymatic subunit of the PI3K (phosphoinositide 3-kinase) pathway associated with cell growth) synergize with CCM gene loss-of-function to generate rapidly growing lesions. METHODS: We recently developed a model of CCM formation that closely reproduces key events in human CCM formation through inducible CCM loss-of-function and PIK3CA gain-of-function in mature mice. In the present study, we use this model to test the ability of rapamycin, a clinically approved inhibitor of the PI3K effector mTORC1, to treat rapidly growing CCMs. RESULTS: We show that both intraperitoneal and oral administration of rapamycin arrests CCM growth, reduces perilesional iron deposition, and improves vascular perfusion within CCMs. CONCLUSIONS: Our findings further establish this adult CCM model as a valuable preclinical model and support clinical testing of rapamycin to treat rapidly growing human CCMs.


Subject(s)
Hemangioma, Cavernous, Central Nervous System , Animals , Humans , Adult , Mice , Hemangioma, Cavernous, Central Nervous System/drug therapy , Hemangioma, Cavernous, Central Nervous System/genetics , Hemangioma, Cavernous, Central Nervous System/metabolism , Endothelial Cells/metabolism , Sirolimus/pharmacology , Phosphatidylinositol 3-Kinases/metabolism , Class I Phosphatidylinositol 3-Kinases/metabolism
13.
Mol Med ; 29(1): 19, 2023 02 06.
Article in English | MEDLINE | ID: mdl-36747144

ABSTRACT

BACKGROUND: With the increasing morbidity and mortality of preeclampsia (PE), it has posed a huge challenge to public health. Previous studies have reported endoplasmic reticulum (ER) stress could contribute to trophoblastic dysfunction which was associated with the N6-methyladenosine (m6A) modification by methyltransferase-like 3 (METTL3), resulting in PE. However, little was known about the relationship between METTL3 and ER stress in PE. Thus, in vitro and in vivo studies were performed to clarify the mechanism about how METTL3 affects the trophoblasts under ER stress in PE and to explore a therapeutic approach for PE. METHODS: An ER stress model in HTR-8/SVneo cells and a preeclamptic rat model were used to study the mechanism and explore a therapeutic approach for PE. Western blot, immunohistochemistry, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and methylated RNA immunoprecipitation (MeRIP)-qPCR were performed to detect the protein, RNA, and methylated transmembrane BAX inhibitor motif containing 6 (TMBIM6) expression levels. The m6A colorimetric and mRNA stability assays were used to measure the m6A levels and TMBIM6 stability, respectively. Short hairpin RNAs (shRNAs) were used to knockdown METTL3 and YTH N6-methyladenosine RNA binding protein 2 (YTHDF2). Flow cytometry and Transwell assays were performed to evaluate the apoptosis and invasion abilities of trophoblasts. RESULTS: Upregulated METTL3 and m6A levels and downregulated TMBIM6 levels were observed in preeclamptic placentas under ER stress. The ER stress model was successfully constructed, and knockdown of METTL3 had a beneficial effect on HTR-8/SVneo cells under ER stress as it decreased the levels of methylated TMBIM6 mRNA. Moreover, overexpression of TMBIM6 was beneficial to HTR-8/SVneo cells under ER stress as it could neutralize the harmful effects of METTL3 overexpression. Similar to the knockdown of METTL3, downregulation of YTHDF2 expression resulted in the increased expression and mRNA stability of TMBIM6. Finally, improved systemic symptoms as well as protected placentas and fetuses were demonstrated in vivo. CONCLUSIONS: METTL3/YTHDF2/TMBIM6 axis exerts a significant role in trophoblast dysfunction resulting in PE while inhibiting METTL3 may provide a novel therapeutic approach for PE.


Subject(s)
Pre-Eclampsia , Animals , Female , Pregnancy , Rats , Apoptosis Regulatory Proteins/metabolism , bcl-2-Associated X Protein/metabolism , Endoplasmic Reticulum Stress/genetics , Membrane Proteins/metabolism , Methyltransferases/genetics , Methyltransferases/metabolism , Pre-Eclampsia/genetics , Pre-Eclampsia/metabolism , RNA , RNA-Binding Proteins , Transcription Factors/metabolism
14.
J Transl Med ; 21(1): 120, 2023 02 13.
Article in English | MEDLINE | ID: mdl-36782197

ABSTRACT

BACKGROUND: Metastasis is the predominant cause of mortality in patients with breast cancer. Long noncoding RNAs (lncRNAs) have been shown to drive important phenotypes in tumors, including invasion and metastasis. However, the lncRNAs involved in metastasis and their molecular and cellular mechanisms are still largely unknown. METHODS: The transcriptional and posttranscriptional processing of LINC00478-associated cytoplasmic RNA (LacRNA) was determined by RT-qPCR, semiquantitative PCR and 5'/3' RACE. Paired-guide CRISPR/cas9 and CRISPR/dead-Cas9 systems was used to knock out or activate the expression of LacRNA. Cell migration and invasion assay was performed to confirm the phenotype of LacRNA. Tail vein model and mammary fat pad model were used for in vivo study. The LacRNA-PHB2-cMyc axis were screened and validated by RNA pulldown, mass spectrometry, RNA immunoprecipitation and RNA-seq assays. RESULTS: Here, we identified a novel cytoplasmic lncRNA, LacRNA (LINC00478-associated cytoplasmic RNA), derived from nucleus-located lncRNA LINC00478. The nascent transcript of LINC00478 full-length (LINC00478_FL) was cleaved and polyadenylated, simultaneously yielding 5' ends stable expressing LacRNA, which is released into the cytoplasm, and long 3' ends of nuclear-retained lncRNA. LINC00478_3'RNA was rapidly degraded. LacRNA significantly inhibited breast cancer invasion and metastasis in vitro and in vivo. Mechanistically, LacRNA physically interacted with the PHB domain of PHB2 through its 61-140-nt region. This specific binding affected the formation of the autophagy degradation complex of PHB2 and LC3, delaying the degradation of the PHB2 protein. Unexpectedly, LacRNA specifically interacted with PHB2, recruited c-Myc and promoted c-Myc ubiquitination and degradation. The negatively regulation of Myc signaling ultimately inhibited breast cancer metastasis. Furthermore, LacRNA and LacRNA-mediated c-Myc signaling downregulation are significantly associated with good clinical outcomes, take advantage of these factors we constructed a prognostic predict model. CONCLUSION: Therefore, our findings propose LacRNA as a potential prognostic biomarker and a new therapeutic strategy.


Subject(s)
RNA, Long Noncoding , Skin Neoplasms , Humans , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Signal Transduction , Proto-Oncogene Proteins c-myc/metabolism , Prognosis , Skin Neoplasms/genetics , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Cell Proliferation , Melanoma, Cutaneous Malignant
15.
Ann Behav Med ; 57(12): 1046-1057, 2023 11 16.
Article in English | MEDLINE | ID: mdl-37549141

ABSTRACT

BACKGROUND: Diabetes is associated with disability development. Healthy behaviors and psychosocial support can help patients manage their disease. PURPOSE: To examine the role of various behavioral and psychological factors in buffering the effect of diabetes on disability development over time in Taiwanese adults. METHODS: Data on 5,131 adults aged ≥50 years were obtained from the Taiwan Longitudinal Study on Aging. A cohort sequential multilevel design was employed to analyze the association between behavioral and psychosocial factors and the risk of disability over a 11-year period. RESULTS: In patients with diabetes, having social support and exercising more than six times a week were associated with 4% and 49% reductions in the risk of disability, respectively (ßdiabetes*socialsupport = -0.285, p = .006; ßdiabetes*exercise3 = -2.612, p = .007). Exercising more than six times a week had an additional significant protective effect against disability development per year (ßdiabetes*exercises3*age = -0.241, p = .038). Depression did not significantly interact with diabetes. However, a trajectory analysis revealed that individuals who had both diabetes and depression had the highest disability score from middle age among all participants. CONCLUSIONS: Engaging in frequent exercise is the most influential factor for reducing the risk of disability in patients with diabetes. Social support provides an additional benefit for disability prevention in individuals with diabetes.


Diabetes can lead to several diseases that affect the heart, vessels, brain, kidneys, and nerves. These diseases can cause disabilities in people with diabetes. Disabilities among people with diabetes lead to higher death rates, depression, and poor life quality. All these have become a great burden to our public health care system. Several past studies let us know healthy behaviors and good social support have positive effects on reducing complications of diabetes. Healthy behaviors, such as healthy diets, regular exercises, and proper stress management. Good social support and participation are known to reduce dementia in people with diabetes. However, it remains unclear about interactions and exact associations among all these factors. This study was designed to find out how health behaviors and social support help people with diabetes reduce the risks of disabilities. By analyzing data from Taiwan Longitudinal Study on Aging, we found that exercising more than six times a week reduced disability risk the most for people with diabetes. Social support, although not as effective as exercising, provided additional positive effects to reducing disability risks of people with diabetes.


Subject(s)
Diabetes Mellitus , Disabled Persons , Adult , Middle Aged , Humans , Longitudinal Studies , Aging , Health Behavior
16.
Future Oncol ; 19(10): 715-726, 2023 Mar.
Article in English | MEDLINE | ID: mdl-37129057

ABSTRACT

Aim: This retrospective study aimed to evaluate the effect of age on cancer relapse and survival in breast cancer patients undergoing different treatments. Methods: The propensity score method was used to correct for disparities between two groups; 2049 young patients were matched to 4053 older patients. Kaplan-Meier curves and Cox proportional hazards models were used to assess disease-free survival. Results: In the original cohort, young patients showed higher lymph node metastasis, hormone-receptor positivity and high Ki-67 levels. After propensity score matching, the disease-free survival of young patients with the luminal B-like subtype who received mastectomy with early stage disease exhibited inferior survival. Conclusion: Decisions about biology-driven systemic treatment strategies for young patients are worthy of discussion with a multidisciplinary tumor board.


Subject(s)
Breast Neoplasms , Humans , Female , Breast Neoplasms/surgery , Breast Neoplasms/pathology , Mastectomy , Retrospective Studies , Prognosis , Neoplasm Recurrence, Local/surgery
17.
Gerontology ; 69(3): 289-300, 2023.
Article in English | MEDLINE | ID: mdl-36167035

ABSTRACT

INTRODUCTION: The Healthy Caregiver Hypothesis (HCH) suggests that caregiving is associated with beneficial health impacts for family caregivers. However, mixed results have been reported, particularly when different levels of caregiving intensity were examined. This study analyzes the relationship between caregiving intensity and three health indicators (functional health, chronic illness, and self-rated general health) among Canadian older adults over 3 years. METHODS: We drew upon a subsample of 11,344 participants aged 65 years and older from the Baseline and Follow-up 1 data of the Canadian Longitudinal Study on Aging and used linear mixed models to test the hypothesis based on different levels of caregiving intensity. RESULTS: Older adults who provided low-intensity care recently or continuously reported better functional health and self-rated health than noncaregivers. In contrast, older adults with low-intensity caregiving responsibility reported more chronic conditions over time compared to noncaregivers, but this association was not found for high-intensity caregivers. DISCUSSION/CONCLUSION: This study elucidates the HCH by incorporating caregiving intensity to understand patterns of better functional health and perceived health but more chronic conditions. The findings yielded from different health indicators suggest the impact of caregiving on health may be domain specific.


Subject(s)
Aging , Caregivers , Humans , Aged , Longitudinal Studies , Canada , Health Status , Chronic Disease
18.
Am J Primatol ; 85(11): e23548, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37661600

ABSTRACT

Provisioning can significantly affect the ranging patterns, foraging strategies, and time budget of wild primates. In this study, we document for the first time, the effects of provisioning on the activity budget and foraging effort in an Asian colobine. Over 3-years, we used an instantaneous scanning method at 10-min intervals to collect data on the activity budget of a semiprovisioned breeding band (SPB) of black-and-white snub-nosed monkeys (Rhinopithecus bieti) (42-70 individuals) at Xiangguqing (Tacheng), Yunnan, China. We then compared the effects of provisioning in our study band with published data on a sympatric wild nonprovisioned breeding band (NPB) of R. bieti (ca. 360 monkeys) at the same field site. The SPB spent 25.6% of their daytime feeding, 17.1% traveling, 46.9% resting, and 10.3% socializing. In comparison, the NPB devoted more time to feeding (34.9%) and socializing (14.1%), less time to resting (31.3%), and was characterized by a greater foraging effort (1.74 versus 0.96, foraging effort = (feeding + traveling)/resting; see Methods). There was no difference between bands in the proportion of their activity budget devoted to traveling (15.7% vs. 17.1%). In addition, the SPB exhibited a more consistent activity budget and foraging effort across all seasons of the year compared to the NPB. These findings suggest that the distribution, availability, and productivity of naturally occurring feeding sites is a major determinant of the behavioral strategies and activity budget of R. bieti. Finally, a comparison of our results with data on six nonprovisioned R. bieti bands indicates that caution must be raised in meta-analyses or intraspecific comparisons of primate behavioral ecology that contain data generated from both provisioned and nonprovisioned groups.

19.
Health Commun ; 38(11): 2408-2418, 2023 10.
Article in English | MEDLINE | ID: mdl-35574639

ABSTRACT

Online weight-loss communities (OWCs) have become increasingly popular for weight management; they enable individuals to monitor (i.e. self-monitoring) and discuss (i.e. social interaction) their weight-loss experiences. This study investigates the relationship between prior weight-loss experiences (success and failure), online social support, and subsequent weight-loss outcome in the context of OWCs and based on self-determination theory. We collected the data of 1465 users from one popular OWC and deployed two logit regression models to estimate the effects of prior weight-loss experiences on subsequent weight-loss success as well as the moderating role of social support. The results revealed that prior successful weight-loss experiences were positively related to subsequent weight-loss outcome, while the relationship between prior failed weight-loss experiences and subsequent weight-loss outcome was negative. Meanwhile, online social support can not only be positively related to subsequent weight-loss outcome, but also buffer the negative role of prior failed weight-loss experiences. Nevertheless, social support had no significant moderating role in the relationship between prior successful weight-loss experiences and subsequent weight-loss outcome. This study contributes to the literature on prior experiences and online social support in the context of OWCs and provides valuable insights to improve participants' engagement and their weight-loss success.


Subject(s)
Social Support , Weight Loss , Humans , Logistic Models
20.
Ann Plast Surg ; 91(1): 48-54, 2023 07 01.
Article in English | MEDLINE | ID: mdl-37216212

ABSTRACT

BACKGROUND: Breast reconstruction has become an integral component of breast cancer treatment, especially for patients who are unable to undergo breast-conserving surgery after neoadjuvant chemotherapy (NAC). We analyzed factors influencing the type of immediate reconstruction surgery after NAC, as well as the complication rates for each surgery type. METHODS: The study included patients with breast cancer who underwent mastectomy following NAC from 2010 to 2021. Clinicopathological characteristics, unplanned reoperation rates, and the duration of postoperative hospitalization were analyzed in patients undergoing autologous tissue reconstruction (ATR, n = 127), implant-based reconstruction (IBR, n = 60), and combined autologous tissue and implant reconstruction (n = 60). RESULTS: A total of 1651 patients who received NAC before mastectomy were enrolled. Among them, 247 (15.0%) patients underwent immediate reconstruction (IR), whereas 1404 underwent mastectomy only. Patients in the IR group were younger ( P < 0.001), had lower body mass index ( P < 0.001), and exhibited earlier clinical ( P = 0.003) and nodal ( P < 0.001) stage than those in the non-IR group. Patients in the ATR group were older ( P < 0.001) and had higher body mass index ( P = 0.007), larger tumor size ( P = 0.024), and more frequent childbearing history ( P = 0.011) than those in the other groups. Complications resulting in unplanned reoperations were more frequent in the IBR group ( P = 0.039). The duration of postoperative hospitalization was longest after ATR ( P = 0.008). CONCLUSIONS: Age and clinical tumor/nodal stage at presentation are associated with IR for patients undergoing mastectomy after NAC. For patients undergoing IR after NAC, ATR may be safer and more suitable than IBR.


Subject(s)
Breast Neoplasms , Mammaplasty , Humans , Female , Mastectomy , Breast Neoplasms/drug therapy , Breast Neoplasms/surgery , Breast Neoplasms/pathology , Neoadjuvant Therapy , Mammaplasty/methods , Reoperation , Postoperative Complications/surgery , Retrospective Studies
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