The evolution of sex roles: The importance of ecology and social environment.

Males and females often have different roles in reproduction, although the origin of these differences has remained controversial. Explaining the enigmatic reversed sex roles where males sacrifice their mating potential and provide full parental care is a particularly long-standing challenge in evolutionary biology. While most studies focused on ecological factors as the drivers of sex roles, recent research highlights the significance of social factors such as the adult sex ratio. To disentangle these propositions, here, we investigate the additive and interactive effects of several ecological and social factors on sex role variation using shorebirds (sandpipers, plovers, and allies) as model organisms that provide the full spectrum of sex role variation including some of the best-known examples of sex-role reversal. Our results consistently show that social factors play a prominent role in driving sex roles. Importantly, we show that reversed sex roles are associated with both male-skewed adult sex ratios and high breeding densities. Furthermore, phylogenetic path analyses provide general support for sex ratios driving sex role variations rather than being a consequence of sex roles. Together, these important results open future research directions by showing that different mating opportunities of males and females play a major role in generating the evolutionary diversity of sex roles, mating system, and parental care.

Alpha/beta oscillations reveal cognitive and affective brain states associated with role taking in a dyadic cooperative game.

Social cooperation often requires taking different roles in order to reach a shared goal. By defining individual tasks, these roles dictate processing demands of the collaborators. The main aim of the present study was to examine the hypothesis that induced alpha and lower beta oscillations provide insights into affective and cognitive brain states during social cooperation. Toward this end, an experimental game was used in which participants had to navigate a Pacman figure through a maze by sending and receiving information about the correct moving direction. Supporting our hypotheses, individual roles taken by the collaborators during gameplay were associated with significant changes in alpha and lower beta power. Furthermore, effects were similar when participants played the Pacman Game with human or computer partners. Findings are discussed from the perspective of the information-via-desynchronization hypothesis proposing that alpha and lower beta power decreases reflect states of enhanced cortical information representation. Overall, experimental games are a useful tool for extending basic research on brain oscillations to the domain of naturalistic social interaction as emphasized by the second-person neuroscience perspective.

Differential gene expression and gut microbiota composition in low-altitude and high-altitude goats.

Previous studies have presented evidence suggesting that altitude exerts detrimental effects on reproductive processes, yet the underlying mechanism remains elusive. Our study employed two distinct goat breeds inhabiting low and high altitudes, and conducted a comparative analysis of mRNA profiles in testis tissues and the composition of gut microbiota. The results revealed a reduced testis size in high-altitude goats. RNA-seq analysis identified the presence of 214 differentially expressed genes (DEGs) in the testis. These DEGs resulted in a weakened immunosuppressive effect, ultimately impairing spermatogenesis in high-altitude goats. Additionally, 16S rDNA amplicon sequencing recognized statistically significant variations in the abundance of the genera Treponema, unidentified_Oscillospiraceae, Desulfovibrio, Butyricicoccus, Dorea, Parabacteroides between the two groups. The collective evidence demonstrated the gut and testis played a synergistic role in causing decreased fertility at high altitudes. Our research provides a theoretical basis for future investigations into the reproductive fitness of male goats.

Speciation by physiological selection of environmentally acquired traits.

A chance mutation affecting a single or extremely few individuals in a continuous population will be quickly diluted through interbreeding. Charles Darwin fully appreciated this difficulty with relying on natural selection alone, and suggested an enabling role for geographical isolation in the origin of species. However, Darwin also believed in evolution by the inheritance of acquired traits and in populations of interbreeding animals, both of which would need a different isolating mechanism to overcome dilution and play a role in animal evolution. Historically disputed, the inheritance of acquired characters is now increasingly accepted as a phenomenon, and Charles Darwin himself is acknowledged as closely pre-empting the type of physiology necessary to mediate it in his hypothesis of 'pangenesis'. In this article, we question how the inheritance of acquired traits might overcome the problem of dilution by interbreeding and contribute to evolution. Specifically, we describe how Darwin's young protégé, George Romanes, developed ideas he discussed with Darwin and extended pangenesis to include a conceivable solution published after Darwin's death: physiological selection of fertility. In light of the 'rediscovery' of pangenesis, here we recount physiological selection as a testable hypothesis to explain how environmentally acquired characteristics could become coupled to the generation of species.

DNA polymerase ε leading strand signature mutations result from defects in its proofreading activity.

The evidence that purified pol2-M644G DNA polymerase (Pol)ε exhibits a highly elevated bias for forming T:dTTP mispairs over A:dATP mispairs and that yeast cells harboring this Polε mutation accumulate A > T signature mutations in the leading strand have been used to assign a role for Polε in replicating the leading strand. Here, we determine whether A > T signature mutations result from defects in Polε proofreading activity by analyzing their rate in Polε proofreading defective pol2-4 and pol2-M644G cells. Since purified pol2-4 Polε exhibits no bias for T:dTTP mispair formation, A > T mutations are expected to occur at a much lower rate in pol2-4 than in pol2-M644G cells if Polε replicated the leading strand. Instead, we find that the rate of A > T signature mutations are as highly elevated in pol2-4 cells as in pol2-M644G cells; furthermore, the highly elevated rate of A > T signature mutations is severely curtailed in the absence of PCNA ubiquitination or Polζ in both the pol2-M644G and pol2-4 strains. Altogether, our evidence supports the conclusion that the leading strand A > T signature mutations derive from defects in Polε proofreading activity and not from the role of Polε as a leading strand replicase, and it conforms with the genetic evidence for a major role of Polδ in replication of both the DNA strands.

Interleukin-21 receptor signaling promotes metabolic dysfunction-associated steatohepatitis-driven hepatocellular carcinoma by inducing immunosuppressive IgA+ B cells.

BACKGROUND: Dysregulation of immune surveillance is tightly linked to the development of metabolic dysfunction-associated steatohepatitis (MASH)-driven hepatocellular carcinoma (HCC); however, its underlying mechanisms remain unclear. Herein, we aimed to determine the role of interleukin-21 receptor (IL-21R) in MASH-driven HCC. METHODS: The clinical significance of IL-21R was assessed in human HCC specimens using immunohistochemistry staining. Furthermore, the expression of IL-21R in mice was assessed in the STAM model. Thereafter, two different MASH-driven HCC mouse models were applied between IL-21R-deficient mice and wild type controls to explore the role of IL-21R in MASH-driven HCC. To further elucidate the potential mechanisms by which IL-21R affected MASH-driven HCC, whole transcriptome sequencing, flow cytometry and adoptive lymphocyte transfer were performed. Finally, flow cytometry, enzyme-linked immunosorbent assay, immunofluorescent staining, chromatin immunoprecipitation assay and western blotting were conducted to explore the mechanism by which IL-21R induced IgA+ B cells. RESULTS: HCC patients with high IL-21R expression exhibited poor relapse-free survival, advanced TNM stage and severe steatosis. Additionally, IL-21R was demonstrated to be upregulated in mouse liver tumors. Particularly, ablation of IL-21R impeded MASH-driven hepatocarcinogenesis with dramatically reduction of lipid accumulation. Moreover, cytotoxic CD8+ T lymphocyte activation was enhanced in the absence of IL-21R due to the reduction of immunosuppressive IgA+ B cells. Mechanistically, the IL-21R-STAT1-c-Jun/c-Fos regulatory axis was activated in MASH-driven HCC and thus promoted the transcription of Igha, resulting in the induction of IgA+ B cells. CONCLUSIONS: IL-21R plays a cancer-promoting role by inducing IgA+ B cells in MASH-driven hepatocarcinogenesis. Targeting IL-21R signaling represents a potential therapeutic strategy for cancer therapy.

Thioredoxin Domain Containing 5 (TXNDC5): Friend or Foe?

This review focuses on the thioredoxin domain containing 5 (TXNDC5), also known as endoplasmic reticulum protein 46 (ERp46), a member of the protein disulfide isomerase (PDI) family with a dual role in multiple diseases. TXNDC5 is highly expressed in endothelial cells, fibroblasts, pancreatic ß-cells, liver cells, and hypoxic tissues, such as cancer endothelial cells and atherosclerotic plaques. TXNDC5 plays a crucial role in regulating cell proliferation, apoptosis, migration, and antioxidative stress. Its potential significance in cancer warrants further investigation, given the altered and highly adaptable metabolism of tumor cells. It has been reported that both high and low levels of TXNDC5 expression are associated with multiple diseases, such as arthritis, cancer, diabetes, brain diseases, and infections, as well as worse prognoses. TXNDC5 has been attributed to both oncogenic and tumor-suppressive features. It has been concluded that in cancer, TXNDC5 acts as a foe and responds to metabolic and cellular stress signals to promote the survival of tumor cells against apoptosis. Conversely, in normal cells, TXNDC5 acts as a friend to safeguard cells against oxidative and endoplasmic reticulum stress. Therefore, TXNDC5 could serve as a viable biomarker or even a potential pharmacological target.

Tumor microenvironment and immune system preservation in early-stage breast cancer: routes for early recurrence after mastectomy and treatment for lobular and ductal forms of disease.

BACKGROUND: Intra-ductal cancer (IDC) is the most common type of breast cancer, with intra-lobular cancer (ILC) coming in second. Surgery is the primary treatment for early stage breast cancer. There are now irrefutable data demonstrating that the immune context of breast tumors can influence growth and metastasis. Adjuvant chemotherapy may be administered in patients who are at a high risk of recurrence. Our goal was to identify the processes underlying both types of early local recurrences. METHODS: This was a case-control observational study. Within 2 years of receiving adjuvant taxan and anthracycline-based chemotherapy, as well as modified radical mastectomy (MRM), early stage IDC and ILC recurred. Vimentin, α-smooth muscle actin (SMA), platelet-derived growth factor (PDGF), matrix metalloproteinase (MMP1), and clustered differentiation (CD95) were investigated. RESULTS: Of the samples in the ductal type group, 25 showed local recurrence, and 25 did not. Six individuals in the lobular-type group did not experience recurrence, whereas seven did. Vimentin (p = 0.000 and 0.021), PDGF (p = 0.000 and 0.002), and CD95 (p = 0.000 and 0.045) expressions were significantly different in ductal and lobular carcinoma types, respectively. Measurement of ductal type was the sole significant difference found in MMP1 (p = 0.000) and α-SMA (p = 0.000). α-SMA and CD95 were two variables that helped the recurrence mechanism in the ductal type according to the pathway analysis. In contrast, the CD95 route is a recurrent mechanism for the lobular form. CONCLUSIONS: While the immune system plays a larger role in ILC, the tumor microenvironment and immune system both influence the recurrence of IDC. According to this study, improving the immune system may be a viable cancer treatment option.

Interbrain substrates of role switching during mother-child interaction.

Mother-child interaction is highly dynamic and reciprocal. Switching roles in these back-and-forth interactions serves as a crucial feature of reciprocal behaviors while the underlying neural entrainment is still not well-studied. Here, we designed a role-controlled cooperative task with dual EEG recording to explore how differently two brains interact when mothers and children hold different roles. When children were actors and mothers were observers, mother-child interbrain synchrony emerged primarily within the theta oscillations and the frontal lobe, which highly correlated with children's attachment to their mothers (self-reported by mothers). When their roles were reversed, this synchrony was shifted to the alpha oscillations and the central area and associated with mothers' perception of their relationship with their children. The results suggested an observer-actor neural alignment within the actor's oscillations, which was related to the actor-toward-observer emotional bonding. Our findings contribute to the understanding of how interbrain synchrony is established and dynamically changed during mother-child reciprocal interaction.

Inroads into saline-alkaline stress response in plants: unravelling morphological, physiological, biochemical, and molecular mechanisms.

MAIN CONCLUSION: This article discusses the complex network of ion transporters, genes, microRNAs, and transcription factors that regulate crop tolerance to saline-alkaline stress. The framework aids scientists produce stress-tolerant crops for smart agriculture. Salinity and alkalinity are frequently coexisting abiotic limitations that have emerged as archetypal mediators of low yield in many semi-arid and arid regions throughout the world. Saline-alkaline stress, which occurs in an environment with high concentrations of salts and a high pH, negatively impacts plant metabolism to a greater extent than either stress alone. Of late, saline stress has been the focus of the majority of investigations, and saline-alkaline mixed studies are largely lacking. Therefore, a thorough understanding and integration of how plants and crops rewire metabolic pathways to repair damage caused by saline-alkaline stress is of particular interest. This review discusses the multitude of resistance mechanisms that plants develop to cope with saline-alkaline stress, including morphological and physiological adaptations as well as molecular regulation. We examine the role of various ion transporters, transcription factors (TFs), differentially expressed genes (DEGs), microRNAs (miRNAs), or quantitative trait loci (QTLs) activated under saline-alkaline stress in achieving opportunistic modes of growth, development, and survival. The review provides a background for understanding the transport of micronutrients, specifically iron (Fe), in conditions of iron deficiency produced by high pH. Additionally, it discusses the role of calcium in enhancing stress tolerance. The review highlights that to encourage biomolecular architects to reconsider molecular responses as auxiliary for developing tolerant crops and raising crop production, it is essential to (a) close the major gaps in our understanding of saline-alkaline resistance genes, (b) identify and take into account crop-specific responses, and (c) target stress-tolerant genes to specific crops.

Epistasis and pleiotropy-induced variation for plant breeding.

Epistasis refers to nonallelic interaction between genes that cause bias in estimates of genetic parameters for a phenotype with interactions of two or more genes affecting the same trait. Partitioning of epistatic effects allows true estimation of the genetic parameters affecting phenotypes. Multigenic variation plays a central role in the evolution of complex characteristics, among which pleiotropy, where a single gene affects several phenotypic characters, has a large influence. While pleiotropic interactions provide functional specificity, they increase the challenge of gene discovery and functional analysis. Overcoming pleiotropy-based phenotypic trade-offs offers potential for assisting breeding for complex traits. Modelling higher order nonallelic epistatic interaction, pleiotropy and non-pleiotropy-induced variation, and genotype × environment interaction in genomic selection may provide new paths to increase the productivity and stress tolerance for next generation of crop cultivars. Advances in statistical models, software and algorithm developments, and genomic research have facilitated dissecting the nature and extent of pleiotropy and epistasis. We overview emerging approaches to exploit positive (and avoid negative) epistatic and pleiotropic interactions in a plant breeding context, including developing avenues of artificial intelligence, novel exploitation of large-scale genomics and phenomics data, and involvement of genes with minor effects to analyse epistatic interactions and pleiotropic quantitative trait loci, including missing heritability.

Exploring the association of gender role expectations of pain and measures of pain sensitization in people with knee osteoarthritis: A cross-sectional study.

OBJECTIVES: First, we explored the association between Gender Role Expectations of Pain (GREP), and psychophysical measures of sensitization in people with knee osteoarthritis (OA). Second, we explored whether the association differed by level of GREP items (high vs low scores). DESIGN: We conducted secondary analyses of a cohort study. Those who were (i) age of ≥40, English or French speaking, ii) diagnosed with knee OA using American College of Rheumatology criteria and iii) consulting with an orthopedic surgeon were included. GREP items pertaining to pain sensitivity and pain endurance of the typical man or woman were rated by males and females respectively. Psychophysical tests consisted of pressure pain thresholds (PPTs), Temporal Summation (TS), and Conditioned Pain Modulation (CPM). Multiple linear regression models for males and females were run with GREP scores (independent variables) and psychophysical tests (dependent variables). Next models stratified on the median split of GREP scores were run. Models were adjusted for age, BMI, pain catastrophizing, anxio-depressive symptoms, and radiographic severity. RESULTS: 280 participants (57% females; age (SD): 63.9 (9.6) and BMI (SD): 31.3 (8.40)) were included. GREP pain sensitivity scores in males were associated with CPM values (ß: 95% CI: 0.09 (0.01 to 0.17)). Males with low GREP pain sensitivity or pain endurance had very small to small positive associations with PPT and CPM values. CONCLUSION: This first exploration of gendered pain sensitivity and pain endurance by males and females has small and clinically unimportant associations with measures of pain sensitization requiring further validation.

MicroRNA-195-5p mediates arsenic-induced cytotoxicity in human lung epithelial cells: Beneficial role of plant-derived tannic acid.

Arsenic (As), a highly toxic metalloid, which causes environmental lung diseases and affects millions of people worldwide. Respiratory epithelial cells are essential for maintaining lung homeostasis, aberrant epithelial damage and death due to exposure to a wide range of environmental pollutants, which are considered to be the initial trigger for many pulmonary diseases. Accumulating evidence has shown that microRNAs (miRNAs) appear to be important players in various normal physiological and pathological processes. Therefore, the present study was carried out to examine the cytotoxic effects of a trivalent form of As (As3+) in normal human bronchial (BEAS-2B) and adenocarcinoma alveolar basal (A549) epithelial cells and the role of miR-195-5p. Further, we also explored the protective effects of a natural dietary polyphenol tannic acid (TA). As3+ (1 µM) treatment in BEAS-2B cells for 24 h induced cytotoxicity by decreasing the cell viability, mitochondrial membrane potential (ΔΨm) and inducing reactive oxygen species (ROS) generation, lipid peroxidation (LPO), cell cycle arrest, and apoptosis, which was associated with a significantly higher level of miR-195-5p expression compared with vehicle control. Forced expression of miR-195-5p alone suppressed cell survival, ΔΨm, regulated cell cycle distribution and induced ROS generation in BEAS-2B cells. As expected, miR-195-5p inhibition effectively rescued BEAS-2B cells from As3+-mediated toxicity, confirming the involvement of miR-195-5p in the cytotoxic effects of As3+. Further, TA pre-treatment expressively alleviated As3+-induced toxicity by suppressing ROS production, miR-195-5p expression, and increasing ΔΨm. These in vitro results indicate that miR-195-5p may be useful as a therapeutic target for treating As3+ toxicity.

Individualized social niches in animals: Theoretical clarifications and processes of niche change.

What are social niches, and how do they arise and change? Our first goal in the present article is to clarify the concept of an individualized social niche and to distinguish it from related concepts, such as a social environment and a social role. We argue that focal individuals are integral parts of individualized social niches and that social interactions with conspecifics are further core elements of social niches. Our second goal in the present article is to characterize three types of processes-social niche construction, conformance, and choice (social NC3 processes)-that explain how individualized social niches originate and change. Our approach brings together studies of behavior, ecology, and evolution and integrates social niches into the broader concept of an individualized ecological niche. We show how clarifying the concept of a social niche and recognizing the differences between the three social NC3 processes enhance and stimulate empirical research.

Physiological roles of human interleukin-17 family.

Interleukin-17 s (IL-17s) are well-known proinflammatory cytokines, and their antagonists perform excellently in the treatment of inflammatory skin diseases such as psoriasis. However, their physiological functions have not been given sufficient attention by clinicians. IL-17s can protect the host from extracellular pathogens, maintain epithelial integrity, regulate cognitive processes and modulate adipocyte activity through distinct mechanisms. Here, we present a systematic review concerning the physiological functions of IL-17s. Our goal is not to negate the therapeutic effect of IL-17 antagonists, but to ensure their safe use and reasonably explain the possible adverse events that may occur in their application.

Orbital Analysis Captures the Existence of a Mixed-Valent CuIII -O-CuII Active-Site and its Role in Water-Assisted Aliphatic Hydroxylation.

The Cu-O-Cu core has been proposed as a potential site for methane oxidation in particulate methane monooxygenase. In this work, we used density functional theory (DFT) to design a mixed-valent CuIII -O-CuII species from an experimentally known peroxo-dicopper complex supported by N-donor ligands containing phenolic groups. We found that the transfer of two-protons and two-electrons from phenolic groups to peroxo-dicopper core takes place, which results to the formation of a bis-µ-hydroxo-dicopper core. The bis-µ-hydroxo-dicopper core converts to a mixed-valent CuIII -O-CuII core with the removal of a water molecule. The orbital and spin density analyses unravel the mixed-valent nature of CuIII -O-CuII . We further investigated the reactivity of this mixed-valent core for aliphatic C-H hydroxylation. Our study unveiled that mixed-valent CuIII -O-CuII core follows a hydrogen atom transfer mechanism for C-H activation. An in-situ generated water molecule plays an important role in C-H hydroxylation by acting as a proton transfer bridge between carbon and oxygen. Furthermore, to assess the relevance of a mixed-valent CuIII -O-CuII core, we investigated aliphatic C-H activation by a symmetrical CuII -O-CuII core. DFT results show that the mixed-valent CuIII -O-CuII core is more reactive toward the C-H bond than the symmetrical CuII -O-CuII core.

Fucosylation and galactosylation in N-glycans of bovine intestinal alkaline phosphatase and their role in its enzymatic activity.

Bovine intestinal alkaline phosphatase (biALP), a membrane-bound plasma metalloenzyme, maintains intestinal homeostasis, regulates duodenal surface pH, and protects against infections caused by pathogenic bacteria. The N-glycans of biALP regulate its enzymatic activity, protein folding, and thermostability, but their structures are not fully reported. In this study, the structures and quantities of the N-glycans of biALP were analyzed by liquid chromatography-electrospray ionization-high energy collision dissociation-tandem mass spectrometry. In total, 48 N-glycans were identified and quantified, comprising high-mannose [6 N-glycans, 33.1 % (sum of relative quantities of each N-glycan)], hybrid (6, 11.9 %), and complex (36, 55.0 %) structures [bi- (13, 26.1 %), tri- (16, 21.5 %), and tetra-antennary (7, 7.4 %)]. These included bisecting N-acetylglucosamine (33, 56.6 %), mono-to tri-fucosylation (32, 53.3 %), mono-to tri-α-galactosylation (16, 20.7 %), and mono-to tetra-ß-galactosylation (36, 58.5 %). No sialylation was identified. N-glycans with non-bisecting GlcNAc (9, 10.3 %), non-fucosylation (10, 13.6 %), non-α-galactosylation (26, 46.2 %), and non-ß-galactosylation (6, 8.4 %) were also identified. The activity (100 %) of biALP was reduced to 37.3 ± 0.2 % (by de-fucosylation), 32.7 ± 2.9 % (by de-α-galactosylation), and 0.2 ± 0.2 % (by de-ß-galactosylation), comparable to inhibition by 10-4 to 101 mM EDTA, a biALP inhibitor. These results indicate that fucosylated and galactosylated N-glycans, especially ß-galactosylation, affected the activity of biALP. This study is the first to identify 48 diverse N-glycan structures and quantities of bovine as well as human intestinal ALP and to demonstrate the importance of the role of fucosylation and galactosylation for maintaining the activity of biALP.

A randomized controlled trial of a self-led, virtual reality-based cognitive behavioral therapy on sick role adaptation in colorectal cancer patients: study protocol.

BACKGROUND: Significant concomitants of the sick role maladaptation in colorectal cancer (CRC) patients include inappropriate cognitions, emotional states, and overt conducts associated to disease. This protocol was developed to implement and evaluate the effects of a self-led, virtual reality-based cognitive behavioral therapy (VR-CBT) on the sick role adaptation among working-age CRC patients. METHODS: This is an assessor-blinded, randomized controlled trail that adheres to the SPIRIT 2013 Statement guidelines. A total of 60 working-age CRC patients will be recruited from the colorectal wards of a cancer center and randomly assigned to the VR-CBT group or attention control (AC) group. The VR-CBT group will receive a 7-sessions VR-CBT targeted to sick role adaptation, while the AC group will receive weekly attention at the same time the VR-CBT group receives the intervention. The sick role adaptation, anxiety and depression, illness perceptions, and quality of life will be measured at baseline, 1, 2 and 3-month after completion of the intervention. Side-effects related to VR in the VR-CBT group will be measured at the end of each session. The participants will receive invitations to participate in semi-structured interviews to explore their experiences with the intervention. DISCUSSION: The positive outcomes and user experience of VR-CBT will advance researches on the effectiveness of psychosocial interventions that aims to promote adaptation to the unexpected sick role on cancer populations. This protocol can be tested as an accessible and feasible alternative to traditional high-cost treatment in a randomized controlled study to improve the outcomes of younger cancer survivors. TRIAL REGISTRATION: The protocol was registered on 21 June, 2023 in Chinese Clinical Trial Registry (No.: ChiCTR2300072699) at https://www.chictr.org.cn/ .

General psychiatry, still in no-man's land after all these years.

Mental health services have changed beyond recognition in my 38-year career. In this editorial I reflect on those changes and highlight the issues that undermine patient care and damage staff morale. In particular, modern mental health services have undermined the therapeutic relationship, the bedrock underpinning all psychiatric treatment.

The dual role of autophagy in the regulation of cancer treatment.

As a catabolic process, autophagy through lysosomes degrades defective and damaged cellular materials to support homeostasis in stressful conditions. Therefore, autophagy dysregulation is associated with the induction of several human pathologies, including cancer. Although the role of autophagy in cancer progression has been extensively studied, many issues need to be addressed. The available evidence suggest that autophagy shows both cytoprotective and cytotoxic mechanisms. This dual role of autophagy in cancer has supplied a renewed interest in the development of novel and effective cancer therapies. Considering this, a deeper understanding of the molecular mechanisms of autophagy in cancer treatment is crucial. This article provides a summary of the recent advances regarding the dual and different mechanisms of autophagy-mediated therapeutic efficacy in cancer.