Molecular Regulation of Thermogenic Mechanisms in Beige Adipocytes.

Adipose tissue is conventionally recognized as a metabolic organ responsible for storing energy. However, a proportion of adipose tissue also functions as a thermogenic organ, contributing to the inhibition of weight gain and prevention of metabolic diseases. In recent years, there has been significant progress in the study of thermogenic fats, particularly brown adipose tissue (BAT). Despite this progress, the mechanism underlying thermogenesis in beige adipose tissue remains highly controversial. It is widely acknowledged that beige adipose tissue has three additional thermogenic mechanisms in addition to the conventional UCP1-dependent thermogenesis: Ca2+ cycling thermogenesis, creatine substrate cycling thermogenesis, and triacylglycerol/fatty acid cycling thermogenesis. This paper delves into these three mechanisms and reviews the latest advancements in the molecular regulation of thermogenesis from the molecular genetic perspective. The objective of this review is to provide readers with a foundation of knowledge regarding the beige fats and a foundation for future research into the mechanisms of this process, which may lead to the development of new strategies for maintaining human health.

Initiating and Maintaining Complete Decongestive Therapy Self-Management of Lymphedema Among Breast Cancer Survivors: Descriptive Qualitative Study.

PURPOSE: This study aimed to identify determinants that promote the initiation and maintenance of complete decongestive therapy (CDT) as well as effective strategies for mitigating barriers to self-management of lymphedema among breast cancer survivors. METHODS: A descriptive and qualitative design was used. In-depth interviews were conducted with 13 breast cancer survivors who were managing breast cancer-related lymphedema. Interviews were transcribed verbatim. An iterative descriptive data analysis method was employed to examine the data, compare codes, challenge interpretations, and inductively identify themes. RESULTS: A realization that lymphedema requires daily self-management was the primary determinant leading breast cancer survivors to initiate CDT self-management. The determinants for maintaining daily CDT self-management included the perceived effectiveness of CDT, being willing to assume accountability, and perceived efficacy to undertake CDT. Developing strategies to integrate CDT regimens into daily life is key to maintaining CDT self-management of lymphedema. Three core concepts mediate initiation and maintenance of CDT self-management: understanding lymphedema as a chronic condition that can be managed with CDT self-management, being worried about lymphedema exacerbation, and having support from patient peers and family. CONCLUSIONS: Interventions should be tailored to promote the initiation and maintenance of CDT self-management. While clinicians provided knowledge-based and clinical skills-based information, patient peers provided daily life examples, and real-life implementation strategies for CDT self-management. Ongoing patient-provider and patient-peer communication functioned as effective support for maintaining CDT self-management. Reliable and realistic methods of symptom self-assessment are important for maintaining CDT at home.

Current genetic strategies to investigate gene functions in Trichoderma reesei.

The filamentous fungus Trichoderma reesei (teleomorph Hypocrea jecorina, Ascomycota) is a well-known lignocellulolytic enzymes-producing strain in industry. To increase the fermentation titer of lignocellulolytic enzymes, random mutagenesis and rational genetic engineering in T. reesei were carried out since it was initially found in the Solomon Islands during the Second World War. Especially the continuous exploration of the underlying regulatory network during (hemi)cellulase gene expression in the post-genome era provided various strategies to develop an efficient fungal cell factory for these enzymes' production. Meanwhile, T. reesei emerges competitiveness potential as a filamentous fungal chassis to produce proteins from other species (e.g., human albumin and interferon α-2b, SARS-CoV-2 N antigen) in virtue of the excellent expression and secretion system acquired during the studies about (hemi)cellulase production. However, all the achievements in high yield of (hemi)cellulases are impossible to finish without high-efficiency genetic strategies to analyze the proper functions of those genes involved in (hemi)cellulase gene expression or secretion. Here, we in detail summarize the current strategies employed to investigate gene functions in T. reesei. These strategies are supposed to be beneficial for extending the potential of T. reesei in prospective strain engineering.

A Multiple Case Study of Latina Breast Cancer Survivors Returning to Work With Breast Cancer-Related Lymphedema: Adaptation, Resilience, and Quality of Life.

Introduction: Breast cancer-related lymphedema (BCRL), a side effect of cancer treatment, may negatively impact the ability to perform work. Factors such as delayed diagnosis, late-stage disease, and a high percentage of service occupations may challenge work choices for Latinas after BCRL diagnosis. Methods: Our multiple case study explored work experiences and quality of life (QOL) for Hispanic/Latina survivors. Participants completed demographic and short form-36 (SF-36) surveys. Semi-structured interviews focused on how work environment, self-management, and QOL were influenced by BCRL. Thematic analysis of cases used In Vivo and descriptive coding and constant cross-case comparative methods. Results: Analysis illustrated how Hispanic/Latina survivors perceive the influence of BCRL on work experience as requiring adaptation and personal resilience. Participants identified BCRL knowledge gap challenges and described coping with physical, psychosocial, and work activity changes. They described creative work adaptations and discussed BCRL's impact on both positive and negative interpersonal perceptions. Strong support from family, friends, and colleagues contributed to improved QOL and continued work activities. Conclusion: Future research should incorporate coping strategies and creative management of BCRL to optimize work activities across the lifespan. These strategies can provide guidance for the creation of survivorship care plans, education of healthcare professionals (HCPs), and lifelong occupational support.

Genome-wide characterization of lncRNAs and mRNAs in muscles with differential intramuscular fat contents.

Meat quality is one of the most important traits in pig production. Long non-coding RNAs (lncRNAs) have been involved in diverse biological processes such as muscle development through regulating gene expression. However, studies on lncRNAs lag behind and a comparatively small number of lncRNAs have been identified in pigs. Also, the effects of lncRNAs on meat quality remain to be characterized. Here, we analyzed lncRNAs in longissimus thoracis (LT) and semitendinosus (ST) muscles, being different in meat quality, with RNA-sequencing technology. A total of 500 differentially expressed lncRNAs (DELs) and 2,094 protein-coding genes (DEGs) were identified. Through KEGG analysis on DELs, we first made clear that fat deposition might be the main reason resulting in the differential phenotype of LT and ST, for which cGMP-PKG and VEGF signaling pathways were the most important ones. In total, forty-one key DELs and 50 DEGs involved in the differential fat deposition were then characterized. One of the key genes, cAMP-response element binding protein 1, was selected to confirm its role in porcine adipogenesis with molecular biology methods and found that it promotes the differentiation of porcine preadipocytes, consistent with its higher expression level and intramuscular fat contents in LT than that in ST muscle. Furthermore, through integrated analysis of DELs and DEGs, transcription factors important for differential fat deposition were characterized among which BCL6 has the most target DEGs while MEF2A was targeted by the most DELs. The results provide candidate genes crucial for meat quality, which will contribute to improving meat quality with molecular-breeding strategies.

Alternative Splicing Isoforms of Porcine CREB Are Differentially Involved in Transcriptional Transactivation.

The cAMP response element-binding protein (CREB), a basic leucine zipper transcription factor, is involved in the activation of numerous genes in a variety of cell types. The CREB gene is rich in alternative splicing (AS) events. However, studies on the AS of CREB genes in pigs are limited, and few reports have compared the roles of isoforms in activating gene expression. Here, five AS transcripts, V1-5, were characterized by RT-PCR and two, V3 and V5, were new identifications. Both V1 and V2 have all the functional domains of the CREB protein, with similar tissue expression profiles and mRNA stability, suggesting that they have similar roles. The transcriptional transactivation activities of four isoforms encoding complete polypeptides were analyzed on the expression of the B-cell CLL/lymphoma 2-like protein 2 and the poly (A)-binding protein, nuclear 1 genes with a dual-luciferase reporter system, and differential activities were observed. Both V1 and V2 have promoting effects, but their roles are gene-specific. V3 has no effect on the promoter of the two genes, while V4 functions as a repressor. The mechanisms underlying the differential roles of V1 and V2 were analyzed with RNA-seq, and the genes specifically regulated by V1 and V2 were identified. These results will contribute to further revealing the role of CREB and to analyzing the significance of AS in genes.

Notch3 regulates ferroptosis via ROS-induced lipid peroxidation in NSCLC cells.

Ferroptosis is type of programmed cell death, which is known to be involved in certain cancers. Notch3 signaling is reported to be involved in the tumorigenesis of non-small-cell lung cancer (NSCLC) and regulates iron metabolism, lipid synthesis, and oxidative stress in some tissues. However, whether Notch3 signaling regulates ferroptosis is unclear. In this study, we found that ferroptosis inhibitors, ferrostatin-1 and liproxstatin-1, protected against cell death induced by Notch3 knockdown and that Notch3 knockdown initiated ferroptosis in NSCLC cells by increasing reactive oxygen species (ROS) levels, lipid peroxidation, and Fe2+ levels, accompanied by downregulation of glutathione peroxidase 4 (GPX4) and peroxiredoxin6 (PRDX6). Conversely, Notch3 intracellular domain overexpression suppressed erastin-induced ferroptosis, which was synergistically enhanced by MJ33 in H1299 cells via a decrease in ROS levels and lipid peroxidation, accompanied by upregulation of GPX4 and PRDX6. Moreover, Notch3 knockdown decreased tumorigenesis in vivo with downregulation of GPX4 and PRDX6. In summary, here we have identified Notch3 as a potential negative regulator of ferroptosis in NSCLC.

Characterization of Alternative Splicing Events in Porcine Skeletal Muscles with Different Intramuscular Fat Contents.

Meat quality is one of the most important economic traits in pig breeding and production. Intramuscular fat (IMF) is a major factor that improves meat quality. To better understand the alternative splicing (AS) events underlying meat quality, long-read isoform sequencing (Iso-seq) was used to identify differential (D)AS events between the longissimus thoracis (LT) and semitendinosus (ST), which differ in IMF content, together with short-read RNA-seq. Through Iso-seq analysis, we identified a total of 56,789 novel transcripts covering protein-coding genes, lncRNA, and fusion transcripts that were not previously annotated in pigs. We also identified 456,965 AS events, among which 3930 were DAS events, corresponding to 2364 unique genes. Through integrative analysis of Iso-seq and RNA-seq, we identified 1174 differentially expressed genes (DEGs), among which 122 were DAS genes, i.e., DE-DAS genes. There are 12 overlapped pathways between the top 20 DEGs and DE-DAS genes, as revealed by KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis, indicating that DE-DAS genes play important roles in the differential phenotype of LT and ST. Further analysis showed that upregulated DE-DAS genes are more important than downregulated ones in IMF deposition. Fatty acid degradation and the PPAR (peroxisome proliferator-activated receptor) signaling pathway were found to be the most important pathways regulating the differential fat deposition of the two muscles. The results update the existing porcine genome annotations and provide data for the in-depth exploration of the mechanisms underlying meat quality and IMF deposition.

The impact of breast cancer-related lymphedema on rural and small-town Survivors' return-to-work and quality of life: A multiple-case study.

BACKGROUND: Breast cancer-related lymphedema (BCRL) is a lifelong condition. Millions who develop breast cancer are younger than retirement age and at a lifetime risk for developing BCRL. Rural and small-town survivors may face unique challenges in terms of access to health care and BCRL/survivorship resources. This multiple-case study describes how BCRL influences the work experiences and quality of life (QoL) of survivors living in rural and small towns in Missouri. METHODS AND MATERIALS: Thirteen survivors from rural and small towns in Missouri completed semi-structured interviews and a standardized QoL instrument. Cases were analyzed using in-vivo and open-coding techniques and constant cross-case comparative methods. Twelve of the 13 participants' data are synthesized into themes to represent an illustrative case. The 13th case is presented as a contradictory (rival) case. RESULTS: Four themes are represented within the illustrative case - multiple medical encounters; the development of self-care routines; the reciprocity of work/live activities, triggers, and adjustments; and rural/small-town cultural impact. Upon BCRL diagnosis, survivors received intensive treatments, eventually establishing self-care routines. Survivors identified strategies for working around their BCRL when completing work and home responsibilities. The contradictory (rival) case was more recently diagnosed and, as such, had not established self-care and coping mechanisms in the same way. CONCLUSIONS AND IMPLICATIONS: Survivors alleviate BCRL symptoms and improve their QoL by establishing self-care strategies. This provides guidance for client-centered survivorship care-planning and occupational rehabilitation of rural survivors with BCRL. This study provides the foundation for developing information for rural survivors that supports mental preparation and coping skills for BCRL self-management.

The influence of breast cancer related lymphedema on women's return-to-work.

BACKGROUND: Lymphedema is one of the major treatment complications following breast cancer surgery and radiation. As the majority of women who develop breast cancer are at the age of employment, occupational functioning and employment are issues of concern. This study is novel in exploring the ways that lymphedema affects their work experience. METHODS: A multiple-case study methodology drawn from Yin's definition was employed. A total of 13 female survivors who developed breast cancer-related lymphedema participated by completing a survey and a 60-min semi-structured interview. RESULTS: Four main themes emerged: (1) breast cancer-related lymphedema affects physical and emotional functioning associated with work; (2) ongoing treatment for breast cancer-related lymphedema creates challenges for work; (3) environmental factors affect the return-to-work experience; and (4) personal factors play a key role in adjusting to return-to-work. CONCLUSION: Both breast cancer-related lymphedema and its treatment have direct and indirect effects on work, with environmental and personal factors also shaping the work-return experience. This study suggests that breast cancer survivors with lymphedema who wish to return to work face potential barriers, and that gaps remain in the availability of supports.

A nurse's twenty-four-year journey with breast cancer-related lymphedema.

BACKGROUND: Lymphedema is one of the major complications following breast cancer treatment. The majority of women who develop breast cancer are in their years of employment. Occupational functioning and employment are issues of significant concern among women with breast cancer-related lymphedema (BCRL). We present a single-case study of a nurse living with BCRL for more than two decades in the Midwestern United States, as an exemplar to explore the 'return-to-work' phenomenon. METHODS: A sixty-minute, semi-structured interview was conducted with a selected single case ("Linda"), following a pre-interview survey. Themes and sub-concepts were generated through constant-comparison of evidence within the case. RESULTS: Themes included: the feeling of being lost, functional impairments related to BCRL and bandaging, being limited yet not being limited, and experiencing different challenges with different jobs. Overall, returning to work with BCRL was a complex phenomenon involving interactions of the disease process, the work activity, the individual, and an array of contextual factors. CONCLUSIONS: Linda's struggles, efforts, and adaptations at different career points were revealing and exemplified how individuals navigate the journey of returning to work with BCRL.

Lymphedema symptoms and limb measurement changes in breast cancer survivors treated with neoadjuvant chemotherapy and axillary dissection: results of American College of Surgeons Oncology Group (ACOSOG) Z1071 (Alliance) substudy.

PURPOSE: Lymphedema is a potential complication of breast cancer treatment. This longitudinal substudy aimed to prospectively assess arm measurements and symptoms following neoadjuvant chemotherapy and axillary dissection in the ACOSOG/Alliance Z1071 trial to characterize the optimal approach to define lymphedema. METHODS: Z1071 enrolled patients with cT0-4, N1-2, M0 disease treated with neoadjuvant chemotherapy. All patients underwent axillary dissection. Bilateral limb volumes, circumferences, and related symptoms were assessed pre-surgery, 1-2 weeks post-surgery, and semiannually for 36 months. Lymphedema definitions included volume increase ≥ 10% or limb circumference increase ≥ 2 cm. Symptoms were assessed by the Lymphedema Breast Cancer Questionnaire. RESULTS: In 488 evaluable patients, lymphedema incidence at 3 years by ≥ 10%-volume-increase was 60.3% (95% CI 55.0-66.2%) and by ≥ 2 cm-circumference increase was 75.4% (95% CI 70.8-80.2%). Symptoms of arm swelling and heaviness decreased from post-surgery for the first 18 months and then were relatively stable. The 3-year cumulative incidence of arm swelling and heaviness was 26.0% (95% CI 21.7-31.1%) and 30.9% (95% CI 26.3-36.3%), respectively. There was limited agreement between the two measurements (kappa 0.27) and between symptoms and measurements (kappa coefficients ranging from 0.05-0.09). CONCLUSIONS: Lymphedema incidence by limb volume and circumference gradually increased over 36 months post-surgery, whereas lymphedema symptoms were much lower. These findings underscore the importance of prospective surveillance and evaluation of both limb measurements and symptom assessment. Lymphedema incidence rates varied by definition. We recommend that ≥ 10% volume change criterion be used for lymphedema evaluation for referral for specialist care. TRIAL REGISTRATION: NCT00881361.

Return to work among breast cancer survivors: A literature review.

PURPOSE: Breast cancer survivors in their employment years are likely to try to go back to work after the primary treatment. Because the literature on return to work among breast cancer survivors is limited, we have undertaken a review of the literature to summarize what is known, including identifying important contributing variables and outcomes. This knowledge may be used to develop hypotheses and potential interventions to support breast cancer survivors who wish to return to work. METHOD: We searched the following databases: CINAHL, MEDLINE, SCOUP, and PUBMED, within a 10-year timeframe (2004 to 2014). RESULTS: The majority of reviewed articles (N = 25) focused on three outcomes: return-to-work period, work ability, and work performance. The most frequently studied independent variables were collapsed into the following groups: health and well-being, symptoms and functioning, work demands and work environment, individual characteristics, and societal and cultural factors. Gaps in the literature include evidence of effective interventions to support return to work among breast cancer survivors and research to better understand the roles of government and business-related policy. CONCLUSION: All the studies reported a reduced work engagement and work ability. Employment status and work performance is associated with a combination of individual factors, work environment, culture, and resources. IMPLICATIONS: Significant gaps are apparent in the literature addressing breast cancer survivorship and return to work. This is a complex problem and it will likely require interdisciplinary research teams to develop effective and feasible interventions for this population.