ATG8-Binding UIM Proteins Define a New Class of Autophagy Adaptors and Receptors.

During autophagy, vesicle dynamics and cargo recruitment are driven by numerous adaptors and receptors that become tethered to the phagophore through interactions with lipidated ATG8/LC3 decorating the expanding membrane. Most currently described ATG8-binding proteins exploit a well-defined ATG8-interacting motif (AIM, or LC3-interacting region [LIR]) that contacts a hydrophobic patch on ATG8 known as the LIR/AIM docking site (LDS). Here we describe a new class of ATG8 interactors that exploit ubiquitin-interacting motif (UIM)-like sequences for high-affinity binding to an alternative ATG8 interaction site. Assays with candidate UIM-containing proteins together with unbiased screens identified a large collection of UIM-based ATG8 interactors in plants, yeast, and humans. Analysis of a subset also harboring ubiquitin regulatory X (UBX) domains revealed a role for UIM-directed autophagy in clearing non-functional CDC48/p97 complexes, including some impaired in human disease. With this new class of adaptors and receptors, we greatly extend the reach of selective autophagy and identify new factors regulating autophagic vesicle dynamics.

A Diversity of Selective Autophagy Receptors Determines the Specificity of the Autophagy Pathway.

The clearance of surplus, broken, or dangerous components is key for maintaining cellular homeostasis. The failure to remove protein aggregates, damaged organelles, or intracellular pathogens leads to diseases, including neurodegeneration, cancer, and infectious diseases. Autophagy is the evolutionarily conserved pathway that sequesters cytoplasmic components in specialized vesicles, autophagosomes, which transport the cargo to the degradative compartments (vacuoles or lysosomes). Research during the past few decades has elucidated how autophagosomes engulf their substrates selectively. This type of autophagy involves a growing number of selective autophagy receptors (SARs) (e.g., Atg19 in yeasts, p62/SQSTM1 in mammals), which bind to the cargo and simultaneously engage components of the core autophagic machinery via direct interaction with the ubiquitin-like proteins (UBLs) of the Atg8/LC3/GABARAP family and adaptors, Atg11 (in yeasts) or FIP200 (in mammals). In this Review, we critically discuss the biology of the SARs with special emphasis on their interactions with UBLs.

Maize lipid droplet-associated protein 2 is recruited by a virus to enhance viral multiplication and infection through regulating cellular fatty acid metabolism.

Pathogen infection induces massive reprogramming of host primary metabolism. Lipid and fatty acid (FA) metabolism is generally disrupted by pathogens and co-opted for their proliferation. Lipid droplets (LDs) that play important roles in regulating cellular lipid metabolism are utilized by a variety of pathogens in mammalian cells. However, the function of LDs during pathogenic infection in plants remains unknown. We show here that infection by rice black streaked dwarf virus (RBSDV) affects the lipid metabolism of maize, which causes elevated accumulation of C18 polyunsaturated fatty acids (PUFAs) leading to viral proliferation and symptom development. The overexpression of one of the two novel LD-associated proteins (LDAPs) of maize (ZmLDAP1 and ZmLDAP2) induces LD clustering. The core capsid protein P8 of RBSDV interacts with ZmLDAP2 and prevents its degradation through the ubiquitin-proteasome system mediated by a UBX domain-containing protein, PUX10. In addition, silencing of ZmLDAP2 downregulates the expression of FA desaturase genes in maize, leading to a decrease in C18 PUFAs levels and suppression of RBSDV accumulation. Our findings reveal that plant virus may recruit LDAP to regulate cellular FA metabolism to promote viral multiplication and infection. These results expand the knowledge of LD functions and viral infection mechanisms in plants.

Powering prescription: Mitochondria as "Living Drugs" - Definition, clinical applications, and industry advancements.

Mitochondria's role as engines and beacons of metabolism and determinants of cellular health is being redefined through their therapeutic application as "Living Drugs" (LDs). Artificial mitochondrial transfer/transplant (AMT/T), encompassing various techniques to modify, enrich, or restore mitochondria in cells and tissues, is revolutionizing acellular therapies and the future of medicine. This article proposes a necessary definition for LDs within the Advanced Therapeutic Medicinal Products (ATMPs) framework. While recognizing different types of LDs as ATMPs, such as mesenchymal stem cells (MSCs) and chimeric antigen receptor T (CAR T) cells, we focus on mitochondria due to their unique attributes that distinguish them from traditional cell therapies. These attributes include their inherent living nature, diverse sources, industry applicability, validation, customizability for therapeutic needs, and their capability to adapt and respond within recipient cells. We trace the journey from initial breakthroughs in AMT/T to the current state-of-the-art applications by emerging innovative companies, highlighting the need for manufacturing standards to navigate the transition of mitochondrial therapies from concept to clinical practice. By providing a comprehensive overview of the scientific, clinical, and commercial landscape of mitochondria as LDs, this article contributes to the essential dialogue among regulatory agencies, academia, and industry to shape their future in medicine.

Polyunsaturated fatty acids promote the rapid fusion of lipid droplets in Caenorhabditis elegans.

Lipid droplets (LDs) are intracellular organelles that dynamically regulate lipids and energy homeostasis in the cell. LDs can grow through either local lipid synthesis or LD fusion. However, how lipids involving in LD fusion for LD growth is largely unknown. Here, we show that genetic mutation of acox-3 (acyl-CoA oxidase), maoc-1 (enoyl-CoA hydratase), dhs-28 (3-hydroxylacyl-CoA dehydrogenase), and daf-22 (3-ketoacyl-CoA thiolase), all involved in the peroxisomal ß-oxidation pathway in Caenorhabditis elegans, led to rapid fusion of adjacent LDs to form giant LDs (gLDs). Mechanistically, we show that dysfunction of peroxisomal ß-oxidation results in the accumulation of long-chain fatty acid-CoA and phosphocholine, which may activate the sterol-binding protein 1/sterol regulatory element-binding protein to promote gLD formation. Furthermore, we found that inactivation of either FAT-2 (delta-12 desaturase) or FAT-3 and FAT-1 (delta-15 desaturase and delta-6 desaturase, respectively) to block the biosynthesis of polyunsaturated fatty acids (PUFAs) with three or more double bonds (n≥3-PUFAs) fully repressed the formation of gLDs; in contrast, dietary supplementation of n≥3-PUFAs or phosphocholine bearing these PUFAs led to recovery of the formation of gLDs in peroxisomal ß-oxidation-defective worms lacking PUFA biosynthesis. Thus, we conclude that n≥3-PUFAs, distinct from other well-known lipids and proteins, promote rapid LD fusion leading to LD growth.

Transcriptional analysis of the expression and prognostic value of lipid droplet-localized proteins in hepatocellular carcinoma.

The accumulation of lipid droplets (LDs) in hepatocytes is the main pathogenesis in nonalcoholic fatty liver disease (NAFLD), which is also the key risk factor for the progression of hepatocellular carcinoma (HCC). LDs behaviors are demonstrated to be associated with HCC advancement, and are tightly regulated by a subset protein localized on the surface of LDs. However, the role of LDs-localized protein in HCC has been rarely investigated. This study is focused on the transcriptional dynamic and prognostic value of LDs-localized protein in HCC. Firstly, we summarized the known LDs-localized proteins, which are demonstrated by immunofluorescence according to previous studies. Next, by the use of GEPIA/UALCAN/The Human Protein Atlas databases, we screened the transcriptional change in tumor and normal liver tissues, and found that 13 LDs-localized proteins may involve in the progression of HCC. Then we verified the transcriptional changes of 13 LDs-localized proteins by the use of HCC samples. Moreover, based on the assays of fatty liver of mice and human NAFLD liver samples, we found that the hepatic steatosis mainly contributed to the transcriptional change of selected LDs-localized proteins, indicating the involvement of these LDs-localized proteins in the negative role of NAFLD in HCC progression. Finally, we focused on the role of PLIN3 in HCC, and revealed that NAFLD status significantly promoted PLIN3 transcription in HCC tissue. Functional studies revealed that PLIN3 knockdown significantly limited the migration and chemosensitivity of hepatoma cells, suggesting the positive role of PLIN3 in HCC progression. Our study not only revealed the transcriptional change and prognostic value of lipid droplet-localized proteins in HCC, but also built the correlation between HCC and hepatic steatosis.

Retinal detachment in Loeys-Dietz syndrome.

Loeys-Dietz syndrome (LDS) is an autosomal-dominant connective-tissue disorder with vascular and musculoskeletal abnormalities similar to Marfan syndrome. However, unlike Marfan, retinal detachment (RD) is rarely reported, and screening protocols do not currently feature ophthalmic assessment or RD counseling. We report a 5-generation family affected by LDS, where RD occurred in six eyes of four individuals. The proband was an 84-year-old male recently diagnosed with type-V LDS (TGFß3 pathogenic variant c.899G>A, p.(Arg300Gln)). Further investigation was undertaken into the family's medical history. The proband experienced bilateral rhegmatogenous RD at age 60, requiring emergency surgical repair. Other notable ophthalmic features include unusual keratometry, abnormal biometry, and severe hayfever requiring long-term sodium cromoglycate treatment. The proband's sister, father, and uncle had also experienced RDs, all prior to LDS diagnosis. This series demonstrates that RD risk may be significant in LDS, and on occasion the presenting clinical feature. We suggest ophthalmic examination should be added to the initial assessment LDS patients, and patients informed of the early warning symptoms of retinal detachment. As in Marfan syndrome, LDS patients may exhibit cornea plana and abnormal corneal topography, producing atypical biometry. They may also present with allergic conjunctivitis, and awareness of these signs might facilitate earlier diagnosis.

Dual living donor organ transplants.

INTRODUCTION: Dual organ donation and transplantation from living donors (LDs) is a rare practice. Dual organ transplants can be done from the same LD or from different LDs and either simultaneously or sequentially. Simultaneous dual organ transplants from the same LD are of considerable concern due to the magnitude of the donor procedure. METHODS AND RESULTS: According to the UNOS/OPTN and IPTR databases, the US experience of LD dual organ transplants from 1981 to 2021 comprised 101 simultaneous or sequential dual organ transplants from the same LD and 111 transplants from different LDs for a total of 212 LD dual transplants. The first simultaneous or sequential dual organ transplants from either the same LD or different LDs were pancreas-kidney transplants (n = 92). Four additional LD organ transplant combinations have been performed in the United States: liver-kidney (n = 93), lung-kidney (n = 16), liver-intestine (n = 9), and intestine-kidney (n = 2). Only for dual pancreas-kidney (n = 49) and liver-intestinal transplants (n = 4), organs from the same LD have been procured simultaneously. Importantly, no donor deaths have been reported after any simultaneous or sequential procurement. LD dual organ outcomes in all recipient categories have been excellent. CONCLUSIONS: LD dual organ donation and transplantation is safe and successful. Any potential dual organ LD candidate must be subject to the highest level of evaluation scrutiny. A (dual) organ donor registry is warranted for long-term follow-up.

Differences in imaging and clinical characteristics are associated with higher rates of decompression-fusion versus decompression-alone in women compared to men for lumbar degenerative spondylolisthesis.

PURPOSE: The goals were to ascertain if differences in imaging/clinical characteristics between women and men were associated with differences in fusion for lumbar degenerative spondylolisthesis. METHODS: Patients had preoperative standing radiographs, CT scans, and intraoperative fluoroscopic images. Symptoms and comorbidity were obtained from patients; procedure (fusion-surgery or decompression-alone) was obtained from intraoperative records. With fusion surgery as the dependent variable, men and women were compared in multivariable logistic regression models with clinical/imaging characteristics as independent variables. The sample was dichotomized, and analyses were repeated with separate models for men and women. RESULTS: For 380 patients (mean age 67, 61% women), women had greater translation, listhesis angle, lordosis, and pelvic incidence, and less diastasis and disc height (all p ≤ 0.03). The rate of fusion was higher for women (78% vs. 65%; OR 1.9, p = 0.008). Clinical/imaging variables were associated with fusion in separate models for men and women. Among women, in the final multivariable model, less comorbidity (OR 0.5, p = 0.05), greater diastasis (OR 1.6, p = 0.03), and less anterior disc height (OR 0.8, p = 0.0007) were associated with fusion. Among men, in the final multivariable model, opioid use (OR 4.1, p = 0.02), greater translation (OR 1.4, p = 0.0003), and greater diastasis (OR 2.4, p = 0.0002) were associated with fusion. CONCLUSIONS: There were differences in imaging characteristics between men and women, and women were more likely to undergo fusion. Differences in fusion within groups indicate that decisions for fusion were based on composite assessments of clinical and imaging characteristics that varied between men and women.

Insufficient evidence for the validity of the Language Development Survey and the MacArthur-Bates Communicative Development Inventories as screening tools: A critical review.

BACKGROUND: The Language Development Survey (LDS) and the MacArthur-Bates Communicative Development Inventories (MB-CDI) are two parental report forms that have been productive in providing data on early child language during the past 30 years. The instruments have been used both in studies relating to typical developing children and in screening for language difficulties. AIM: To review the evidence for the LDS and the MB-CDI utility as screening instruments. METHODS: A literature search in PubMed and PsychInfo identified 16 articles based on LDS or MB-CDI that reported statistics pertinent to early screening for language difficulties. MAIN CONTRIBUTION: It was found that most reviewed studies were explorative in nature and tried out different versions of the screening test, including different cut-off values, multiple reference tests, small sample sizes and rarely reported confidence intervals. Spectrum, verification and review biases were common. Moreover, no study could convincingly show that the actual diagnostic accuracy was sufficient for clinical use. CONCLUSIONS: There is insufficient evidence that the LDS or any version of the MB-CDI is a valid tool for screening for language difficulties. Of course, this is not to say that sufficient evidence will not be achieved in future studies, or that the instruments do not work well for purposes other than screening. WHAT THIS PAPER ADDS: What is already known on this subject The LDS and the MB-CDI are two often-used instruments assessing various aspects of early child language by parental reports. Both instruments have also been used in screening for early language difficulties. What this study adds This study reveals that most published studies in which the classification accuracy of LDS and the MB-CDI has been investigated contain serious methodological shortcomings limiting conclusions about their validity. Currently, there is no good evidence about the usefulness of the LDS and the MB-CDI as general screening tools for language difficulties. What are the potential or actual clinical implications of this work? The LDS and MB-CDI should not be used as screening tools for language difficulties until better evidence of their effectiveness has been demonstrated.

Strategy for Non-Orthogonal Multiple Access and Performance in 5G and 6G Networks.

The purpose of this paper is to provide a high-level overview of the most important non-orthogonal multiple access (NOMA) protocols in 5G and 6G networks that incorporate code division within the context of 3GPP standardization. The article's objective is also to look into and compare the various strategies that have been proposed as a solution to the issue of resource distribution to achieve high performance. Many different NOMA plans for 5G and 6G systems have been suggested by a multitude of businesses. NOMA is currently developing in two primary directions: one of them is with power division, and the other is with code division. During the process of standardization carried out by the 3GPP, the attention of the developers was concentrated in the second direction for the application of NOMA schemes in 5G and 6G systems. Hardware communication, also known as D2D communication, performs a significant role in the process of communication between devices. This will increase the efficiency with which network resources are utilized. Devices are now able to interact directly with one another, avoiding the need for transmission nodes. It also serves as one of the approaches to the problem of limited network coverage, which can be improved by utilizing D2D, and as a result fees and energy can be reduced. Increasing the size of the network is one way to achieve this goal, the explained of NOMA technology as well as its primary benefits in wireless technology. The most common variants of code division NOMA and the characteristics of those variants are discussed, as well as the opportunities and challenges associated with implementing those variants. NOMA protocols allow continuous expansion of wireless communication networks, i.e., 5G and 6G, which leads to enhanced performance of the networks.

AmAtg2B-Mediated Lipophagy Regulates Lipolysis of Pupae in Apis mellifera.

Lipophagy plays an important role in regulating lipid metabolism in mammals. The exact function of autophagy-related protein 2 (Atg2) has been investigated in mammals, but research on the existence and functions of Atg2 in Apis mellifera (AmAtg2) is still limited. Here, autophagy occurred in honeybee pupae, which targeted lipid droplets (LDs) in fat body, namely lipophagy, which was verified by co-localization of LDs with microtubule-associated protein 1A/1B light chain 3 beta (LC3). Moreover, AmAtg2 homolog B (AmAtg2B) was expressed specifically in pupal fat body, which indicated that AmAtg2B might have special function in fat body. Further, AmAtg2B antibody neutralization and AmAtg2B knock-down were undertaken to verify the functions in pupae. Results showed that low expression of AmAtg2B at the protein and transcriptional levels led to lipophagy inhibition, which down-regulated the expression levels of proteins and genes related to lipolysis. Altogether, results in this study systematically revealed that AmAtg2B interfered with lipophagy and then caused abnormal lipolysis in the pupal stage.

FOXO3 Deficiency in Neutrophils Drives Colonic Inflammation and Tumorigenesis.

Inflammatory bowel disease (IBD), characterized by infiltration of polymorphonuclear neutrophils (PMNs), increases the risk of colon cancer. PMN activation corresponds to the accumulation of intracellular Lipid Droplets (LDs). As increased LDs are negatively regulated by transcription factor Forkhead Box O3 (FOXO3), we aim to determine the significance of this regulatory network in PMN-mediated IBD and tumorigenesis. Affected tissue of IBD and colon cancer patients, colonic and infiltrated immune cells, have increased LDs' coat protein, PLIN2. Mouse peritoneal PMNs with stimulated LDs and FOXO3 deficiency have elevated transmigratory activity. Transcriptomic analysis of these FOXO3-deficient PMNs showed differentially expressed genes (DEGs; FDR < 0.05) involved in metabolism, inflammation, and tumorigenesis. Upstream regulators of these DEGs, similar to colonic inflammation and dysplasia in mice, were linked to IBD and human colon cancer. Additionally, a transcriptional signature representing FOXO3-deficient PMNs (PMN-FOXO3389) separated transcriptomes of affected tissue in IBD (p = 0.00018) and colon cancer (p = 0.0037) from control. Increased PMN-FOXO3389 presence predicted colon cancer invasion (lymphovascular p = 0.015; vascular p = 0.046; perineural p = 0.03) and poor survival. Validated DEGs from PMN-FOXO3389 (P2RX1, MGLL, MCAM, CDKN1A, RALBP1, CCPG1, PLA2G7) are involved in metabolism, inflammation, and tumorigenesis (p < 0.05). These findings highlight the significance of LDs and FOXO3-mediated PMN functions that promote colonic pathobiology.

Facile Transformation from Rofecoxib to a New Near-Infrared Lipid Droplet Fluorescent Probe and Its Investigations on AIE Property, Solvatochromism and Mechanochromism.

Lipid-related cancers cause a large number of deaths worldwide. Therefore, development of highly efficient Lipid droplets (LDs) fluorescent imaging probes will be beneficial to our understanding of lipid-related cancers by allowing us to track the metabolic process of LDs. In this work, a LDs-specific NIR (λmax = 698 nm) probe, namely BY1, was rationally designed and synthesized via a one-step reaction by integrating triphenylamine (electron-donor group) unit into the structure of rofecoxib. This integration strategy enabled the target BY1 to form a strong Donor-Acceptor (D-A) system and endowed BY1 with obvious aggregation-induced emission (AIE) effect. Meanwhile, BY1 also showed observable solvent effect and reversible mechanochromatic luminescent property, which could be interpreted clearly via density functional theory (DFT) calculations, differential scanning calorimetry (DSC), powder X-ray diffraction (XPRD), and single crystal X-ray data analysis. More importantly, BY1 exhibited highly specific fluorescent imaging ability (Pearson's correlation = 0.97) towards lipid droplets in living HeLa cells with low cytotoxicity. These results demonstrated that BY1 is a new promising fluorescent probe for lipid droplets imaging, and it might be beneficial to facilitate biological research of lipid-related cancers.

A new perspective on NAFLD: Focusing on lipid droplets.

Lipid droplets (LDs) are complex and metabolically active organelles. They are composed of a neutral lipid core surrounded by a monolayer of phospholipids and proteins. LD accumulation in hepatocytes is the distinctive characteristic of non-alcoholic fatty liver disease (NAFLD), which is a chronic, heterogeneous liver condition that can progress to liver fibrosis and hepatocellular carcinoma. Though recent research has improved our understanding of the mechanisms linking LD accumulation to NAFLD progression, numerous aspects of LD biology are either poorly understood or unknown. In this review, we provide a description of several key mechanisms that contribute to LD accumulation in hepatocytes, favouring NAFLD progression. First, we highlight the importance of LD architecture and describe how the dysregulation of LD biogenesis leads to endoplasmic reticulum stress and inflammation. This is followed by an analysis of the causal nexus that exists between LD proteome composition and LD degradation. Finally, we describe how the increase in size of LDs causes activation of hepatic stellate cells, leading to liver fibrosis and hepatocellular carcinoma. We conclude that acquiring a more sophisticated understanding of LD biology will provide crucial insights into the heterogeneity of NAFLD and assist in the development of therapeutic approaches for this liver disease.

Genetic landscape of FOXC2 mutations in lymphedema-distichiasis syndrome: Different mechanism of pathogenicity for mutations in different domains.

Lymphedema-dissociated syndrome (LDS), of which the pathogenesis is not fully understood, afflicts many patients. In this study, we investigated the effect of FOXC2 gene loss-of-function on the development of LDS disease. Two Han Chinese families with LDS were recruited in this study, pathogenic mutations were identified by Sanger sequencing. Reverse-transcription PCR, subcellular localization, dual fluorescein enzymes, and other in vitro experiments were used to study the functional effects of eight FOXC2 mutations. Two pathogenic FOXC2 duplication mutations (c.930_936dup and c.931-937dup) were identified in the two families. Both mutations caused uneven distribution in the nucleus and a chromatin contraction phenotype, weakening the DNA binding activity and transcription activity. We then performed functional analysis on six additional mutations in different domains of FOXC2 that were reported to cause LDS. We found mutations located in the forkhead domain and central region dramatically reduced the transactivation ability, while mutations in activation domain-2 enhanced this ability. All 8 mutations down-regulated the transcription of ANGPT2 and affected the activity of the ERK-RAS pathway, which may cause abnormal formation of lymphatic vessels. Our findings also showed that all 8 mutations decreased the ability of interaction between FOXC2 and the Wnt4 promoter, suggesting mutations in FOXC2 may also affect the Wnt4-Frizzled-RYK signaling pathway, leading the abnormal differentiation of the meibomian glands into hair follicle cells during the embryonic period and causing distichiasis. This study expanded and revealed the potential pathogenesis mechanism.

Fat storage-inducing transmembrane proteins: beyond mediating lipid droplet formation.

Fat storage-inducing transmembrane proteins (FITMs) were initially identified in 2007 as members of a conserved endoplasmic reticulum (ER) resident transmembrane protein gene family, and were found to be involved in lipid droplet (LD) formation. Recently, several studies have further demonstrated that the ability of FITMs to directly bind to triglyceride and diacylglycerol, and the diphosphatase activity of hydrolyzing fatty acyl-CoA, might enable FITMs to maintain the formation of lipid droplets, engage in lipid metabolism, and protect against cellular stress. Based on the distribution of FITMs in tissues and their important roles in lipid droplet biology and lipid metabolism, it was discovered that FITMs were closely related to muscle development, adipocyte differentiation, and energy metabolism. Accordingly, the abnormal expression of FITMs was not only associated with type 2 diabetes and lipodystrophy, but also with cardiac disease and several types of cancer. This study reviews the structure, distribution, expression regulation, and functionality of FITMs and their potential relationships with various metabolic diseases, hoping to provide inspiration for fruitful research directions and applications of FITM proteins. Moreover, this review will provide an important theoretical basis for the application of FITMs in the diagnosis and treatment of related diseases.

Hepatic PLIN5 Deficiency Impairs Lipogenesis through Mitochondrial Dysfunction.

Regulation of lipid droplets (LDs) metabolism is the core of controlling intracellular fatty acids (FAs) fluxes, and perilipin 5 (PLIN5) plays a key role in this process. Our previous studies have found that hepatic PLIN5 deficiency reduces LDs accumulation, but the trafficking of FAs produced from this pathway and the interaction between mitochondria and LDs in this process are largely unknown. Here, we found that the deficiency of PLIN5 decreases LDs accumulation by increasing FAs efflux. In addition, the decreased lipogenesis of PLIN5-deficient hepatocytes is accompanied by mitochondrial dysfunction, suggesting that PLIN5 plays an important role in mediating the interaction between LDs and mitochondria. Importantly, PLIN5 ablation negates oxidative capacity differences of peri-droplet and cytosolic mitochondria. In summary, these data indicate that PLIN5 plays a vital role in maintaining mitochondrial-mediated lipogenesis, which provides an important new perspective on the regulation of liver lipid storage and the relationship between PLIN5 and mitochondria.

Lipid Droplets in Cancer: From Composition and Role to Imaging and Therapeutics.

Cancer is the second most common cause of death worldwide, having its origin in the abnormal growth of cells. Available chemotherapeutics still present major drawbacks, usually associated with high toxicity and poor distribution, with only a small fraction of drugs reaching the tumour sites. Thus, it is urgent to develop novel therapeutic strategies. Cancer cells can reprogram their lipid metabolism to sustain uncontrolled proliferation, and, therefore, accumulate a higher amount of lipid droplets (LDs). LDs are cytoplasmic organelles that store neutral lipids and are hypothesized to sequester anti-cancer drugs, leading to reduced efficacy. Thus, the increased biogenesis of LDs in neoplastic conditions makes them suitable targets for anticancer therapy and for the development of new dyes for cancer cells imaging. In recent years, cancer nanotherapeutics offered some exciting possibilities, including improvement tumour detection and eradication. In this review we summarize LDs biogenesis, structure and composition, and highlight their role in cancer theranostics.

"I Just Wanted Support": Examining How LDS Clergy May Effectively Minister to Sexual and Gender Minority Congregants.

This study explored why members of the Church of Jesus Christ of Latter-day Saints (LDS) who identify as sexual or gender minorities (SGM) speak with clergy regarding their SGM identities, as well as what LDS SGMs find helpful and unhelpful in these conversations. A sample of 25 current or former LDS SGMs participated in semi-structured interviews, which were analyzed using thematic analysis. Participants reported six overarching reasons for talking with clergy, including church procedures, seeking guidance, seeking emotional comfort, seeking repentance, seeking openness, and other people's initiation. Participants reported several ways clergy were helpful, including empathic listening, openness, and affirmative spiritual care. Participants further reported several ways clergy were unhelpful, including punishing, lacking empathic listening, having a limited worldview, and pathologizing. Clergy may benefit from understanding why LDS SGMs are speaking with them, and from utilizing helpful approaches such as empathic listening skills in their ministering efforts.