An AIE-based fluorescent probe to detect peroxynitrite levels in human serum and its cellular imaging.

An AIE-based fluorescent probe was designed to evaluate peroxynitrite levels in complex biological samples. The newly synthesized hydrazone-conjugated probe fluoresces strongly in the presence of peroxynitrite. Clinically, the peroxynitrite levels can be measured in human serum and cellular mitochondria with an LOD of 6.5 nM by fluorescence imaging in vitro.

Assessment of Welfare Problems in Broilers: Focus on Musculoskeletal Problems Associated with Their Rapid Growth.

The growth of the broiler industry has been accompanied with concerns over the environmental and social impacts on intensive production systems, as well as the welfare of the animals themselves. As a result, since the 2000s, there has been growing interest in alternative production systems that improve animal welfare and sustainability. In this context, it is important to prioritize the welfare of broilers in commercial production systems and to use reliable welfare indicators to provide consumers with information about the welfare of the animals they consume. Resource-based measures (RBM) are based on assessing the resources available to the birds in terms of their housing, environment, and management practices, such as stocking density, litter quality, lighting and air quality, etc. Outcome-based measures (OBM), also known as animal-based measures, focus on assessing the actual welfare outcomes for the birds, such as footpad dermatitis, hock burn, contamination or damage to feathers, gait score, mortality, etc. These OBM-based measures are one of the more direct indicators of welfare and can help identify any welfare issues. The present review highlighted the factors that affect animal welfare indicators focused on OBMs which can be used in the commercial broiler farms.

Dietary probiotic Lacticaseibacillus paracasei NSMJ56 modulates gut immunity and microbiota in laying hens.

This study was performed to investigate supplementary effects of probiotic Lacticaseibacillus paracasei NSMJ56 strain on laying performance, egg quality, intestinal histology, antioxidant status, gut immunity and microbiota in laying hens. A total of ninety-six 21-wk-old Hy-Line Brown laying hens were randomly subjected to one of 2 dietary treatments: a control group fed a non-supplemented diet, or a probiotic group fed with a diet supplemented with 1 g of Lacticaseibacillus paracasei NSMJ56 (5 × 108 CFU/kg of diet). The trial lasted for 4 wk. Egg weight was increased (P < 0.05) in laying hens fed probiotic-fed diet compared with the control group. Dietary probiotics did not affect egg quality except for Haugh unit, which was improved (P < 0.05) in the probiotic-fed group. Neither jejunal histology nor cecal short-chain fatty acids were affected by dietary treatments. Dietary probiotics increased the activity of catalase compared with the control group. Flow cytometry analysis revealed that dietary probiotics elevated the CD4+ T cells, but not CD8+ T cells, in jejunal lamina propria. Based on the LEfSe analysis at the phylum and genus levels, Erysipelotrichales, Erysipelotrichia, Flintibater, Dielma, Hespellia, Coprobacter, Roseburia, Anaerotignum, and Coprococcus were enriched in the probiotic group compared with the control group. Taken together, our study showed that dietary probiotics could be used to improve some parameters associated with egg freshness and antioxidant capacity, and to partially alter T cell population and microbial community in laying hens.

Effects of grain-based pecking blocks on productivity and welfare indicators in commercial broiler chickens.

OBJECTIVE: This experiment was conducted to investigate the effect of grain-based pecking blocks on productivity and welfare status at two commercial broiler welfare-certified farms. METHODS: Production and welfare indicators were assessed at two farms (designated Farm A and B). Both farms had two windowless houses with forced tunnel-type ventilation and housed broilers at stocking densities of approximately 16.7 birds/m2 (Farm A) and 16.8 birds/m2 (Farm B). Each house was divided into two or three equal sections and was provided with or without pecking blocks. Grain-based pecking blocks, measuring 25 × 25 × 25 cm, were given to broilers in both farms at 1 block per 1,000 birds. Various parameters including productivity (body weight and flock uniformity), corticosterone levels (in fecal droppings and feathers), footpad dermatitis, hock burn, feather dirtiness, gait score, litter quality, body surface temperature, and volatile fatty acids in fecal samples were assessed at 26 days of age, whereas litter quality was analyzed at 13 and 26 days of age. RESULTS: There were no significant effects of providing pecking blocks on productivity (body weight and uniformity), fecal and feather corticosterone, welfare indicators (i.e., footpad dermatitis, hock burn, feather cleanliness, and gait score), and litter quality (i.e., moisture, nitrogen, and pH). No differences in body surface temperature between the control and enrichment treatments were noted in Farm B, but body surface temperatures of the head (p = 0.029) and legs (p = 0.011) in the enrichment vs. control group were elevated in Farm A. Butyrate concentration in the enrichment vs control group was higher in Farm B (p = 0.023), but this effect was not detected in Farm A. CONCLUSION: It is concluded that grain-based pecking blocks did not affect performance and welfare indicators. Further studies are warranted to elucidate the potential impact of grain-based pecking blocks on gut health indicators.

Research Note: Welfare and stress responses of broiler chickens raised in conventional and animal welfare-certified broiler farms.

The present study was conducted to assess the animal welfare status of broiler chickens raised in conventional and welfare-certified farms. One conventional farm (30,000 birds/house, 1,488 m2/house, 2 houses) and one animal welfare-certified farm (32,000 birds/house, 1,920 m2/house, 2 houses) were selected to measure productivity, stress responses, and animal welfare indicators in 3 broiler flocks (2 farms/season, n = 6 flocks/farm type) during summer, autumn, and spring. Upon farm visits, body weight, uniformity, and animal welfare indicators (i.e., fecal and feather corticosterone, footpad dermatitis, hock burn, feather dirtiness, and gait score) were measured at 26 d posthatch. Also, moisture, nitrogen, and pH of litter, light intensity, ammonia concentration, and body surface temperature of head, chest, and legs were measured. There was no difference in body weight and uniformity between farm types. Fecal corticosterone concentrations were higher (P = 0.021) in welfare-certified vs. conventional farm, but no significant difference was found in feather corticosterone. Welfare-certified vs. conventional farm had lower percentages of hock burn (P = 0.018), feather dirtiness scores (P = 0.009), and gait score (P = 0.040), and there was no difference in footpad dermatitis. Nitrogen content in litter samples tended to be higher in conventional vs. welfare-certified farms (P = 0.094), and there was no difference in moisture and pH between farm types. Ammonia concentration within the broiler houses was not different between 2 farms. However, animal welfare farm was found to be brighter than conventional farm (P < 0.001). The body surface temperature of head, chest, and legs was not different between farm types. In conclusion, the welfare-certified farm had higher welfare measures, including lower hock burn, feather dirtiness, and gait score, confirming an overall improvement in welfare indicators. However, the observation on the elevated feather corticosterone noted in welfare vs. conventionally raised chickens warrants further studies.

The Effect of Low Temperature on Laying Performance and Physiological Stress Responses in Laying Hens.

The present study investigated the effect of low temperature on laying performance, egg quality, body temperature, yolk malondialdehyde, yolk corticosterone, and serum biochemistry in laying hens. A total of 40 laying hens (Hy-Line Brown) aged 36 weeks were housed in one of two environmental chambers kept at 12 ± 4.5 °C (low temperature) or 24 ± 3 °C (normal temperature) for 4 weeks. Low vs. normal temperature significantly increased (p < 0.05) live body weight, feed intake, and feed conversion ratio in laying hens. Skin surface temperature, but not rectal temperature, was decreased in laying hens exposed to low vs. normal temperature. Hens exposed to low temperature laid an intense eggshell color compared with those raised in a normal temperature. Malondialdehyde concentrations in yolk were increased in low-temperature-exposed laying hens compared with those at normal temperature conditions, but this effect was only noted on day 7, post the low-temperature exposure (p = 0.04). Finally, low vs. normal temperature increased the concentrations of total cholesterol and triglyceride in serum. Collectively, this study indicates that exposure to low temperature in laying hens initially disrupted antioxidant system and altered lipid metabolism in laying hens without inducing stress responses.

Peripheral T cell activation, not thymic selection, expands the T follicular helper repertoire in a lupus-prone murine model.

Many autoimmune diseases are characterized by the activation of autoreactive T cells. The T cell repertoire is established in the thymus; it remains uncertain whether the presence of disease-associated autoreactive T cells reflects abnormal T cell selection in the thymus or aberrant T cell activation in the periphery. Here, we describe T cell selection, activation, and T cell repertoire diversity in female mice deficient for B lymphocyte-induced maturation protein (BLIMP)-1 in dendritic cells (DCs) (Prdm1 CKO). These mice exhibit a lupus-like phenotype with an expanded population of T follicular helper (Tfh) cells having a more diverse T cell receptor (TCR) repertoire than wild-type mice and, in turn, develop a lupus-like pathology. To understand the origin of the aberrant Tfh population, we analyzed the TCR repertoire of thymocytes and naive CD4 T cells from Prdm1 CKO mice. We show that early development and selection of T cells in the thymus are not affected. Importantly, however, we observed increased TCR signal strength and increased proliferation of naive T cells cultured in vitro with antigen and BLIMP1-deficient DCs compared to control DCs. Moreover, there was increased diversity in the TCR repertoire in naive CD4+ T cells stimulated in vitro with BLIMP1-deficient DCs. Collectively, our data indicate that lowering the threshold for peripheral T cell activation without altering thymic selection and naive T cell TCR repertoire leads to an expanded repertoire of antigen-activated T cells and impairs peripheral T cell tolerance.

Photothermal Lithography for Realizing a Stretchable Multilayer Electronic Circuit Using a Laser.

Photolithography is a well-established fabrication method for realizing multilayer electronic circuits. However, it is challenging to adopt photolithography to fabricate intrinsically stretchable multilayer electronic circuits fully composed of an elastomeric matrix, due to the opacity of thick stretchable nanocomposite conductors. Here, we present photothermal lithography that can pattern elastomeric conductors and via holes using pulsed lasers. The photothermal-patterned stretchable nanocomposite conductor exhibits 3 times higher conductivity (5940 S cm-1) and 5 orders of magnitude lower resistance change (R/R0 = 40) under a 30% strained 5000th cyclic stretch, compared to those of a screen-printed conductor, based on the percolation network formed by spatial heating of the laser. In addition, a 50 µm sized stretchable via holes can be patterned on the passivation without material ablation and electrical degradation of the bottom conductor. By repeatedly patterning the conductor and via holes, highly conductive and durable multilayer circuits can be stacked with layer-by-layer material integration. Finally, a stretchable wireless pressure sensor and passive matrix LED array are demonstrated, thus showing the potential for a stretchable multilayer electronic circuit with durability, high density, and multifunctionality.

Metal Modulation: An Effortless Tactic for Refining Photoredox Catalysis in Living Cells.

The remarkable impact of photoredox catalytic chemistries has sparked a wave of innovation, opening doors to novel biotechnologies in the realm of catalytic antitumor therapy. Yet, the quest for novel photoredox catalysts (PCs) suitable for living systems, or the enhancement of catalytic efficacy in existing biocompatible PC systems, persists as a formidable challenge. Within this context, we introduce a readily applicable metal modulation strategy that significantly augments photoredox catalysis within living cells, exemplified by a set of metalloporphyrin complexes termed M-TCPPs (M = Zn, Mn, Ni, Co, Cu). Among these complexes, Zn-TCPP emerges as an exceptional catalyst, displaying remarkable photocatalytic activity in the oxidation of nicotinamide adenine dinucleotide (NADH), nicotinamide adenine dinucleotide phosphate (NADPH), and specific amino acids. Notably, comprehensive investigations reveal that Zn-TCPP's superior catalytic prowess primarily arises from the establishment of an efficient oxidative cycle for PC, in contrast to previously reported PCs engaged in reductive cycles. Moreover, theoretical calculations illuminate that amplified intersystem crossing rates and geometry alterations in Zn-TCPP contribute to its heightened photocatalytic performance. In vitro studies demonstrated that Zn-TCPP exhibits therapeutic potential and is found to be effective for photocatalytic antitumor therapy in both glioblastoma G98T cells and 3D multicellular spheroids. This study underscores the transformative role of "metal modulation" in advancing high-performance PCs for catalytic antitumor therapy, marking a significant stride toward the realization of this innovative therapeutic approach.

Phenotypic and functional characteristics of murine CD11c+ B cells which is suppressed by metformin.

Since the description of age-associated or autoimmune-associated B cells (ABCs), there has been a growing interest in the role of these cells in autoimmunity. ABCs are differently defined depending on the research group and are heterogenous subsets. Here, we sought to characterize ABCs in Sle1/2/3 triple congenic (TC) mice, which is a well accepted mouse model of lupus. Compared to follicular (FO) B cells, ABCs have many distinct functional properties, including antigen presentation. They express key costimulatory molecules for T cell activation and a distinct profile of cytokines. Moreover, they exhibit an increased capacity for antigen uptake. ABCs were also compared with germinal center (GC) B cells, which are antigen activated B cell population. There are several phenotypic similarities between ABCs and GC B cells, but GC B cells do not produce proinflammatory cytokines or take up antigen. While T cell proliferation and activation is induced by both FO B and ABCs in an antigen-dependent manner, ABCs induce stronger T cell receptor signaling in naïve CD4+ T cells and preferentially induce differentiation of T follicular helper (Tfh) cells. We found that ABCs exhibit a distinct transcriptomic profile which is focused on metabolism, cytokine signaling and antigen uptake and processing. ABCs exhibit an increase in both glycolysis and oxidative phosphorylation compared to FO B cells. Treatment of ABCs with metformin suppresses antigen presentation by decreasing antigen uptake, resulting in decreased Tfh differentiation. Taken together, these findings define a fundamental connection between metabolism and function within ABCs.

Selective Cell-Cell Adhesion Regulation via Cyclic Mechanical Deformation Induced by Ultrafast Nanovibrations.

The adoption of dynamic mechanomodulation to regulate cellular behavior is an alternative to the use of chemical drugs, allowing spatiotemporal control. However, cell-selective targeting of mechanical stimuli is challenging due to the lack of strategies with which to convert macroscopic mechanical movements to different cellular responses. Here, we designed a nanoscale vibrating surface that controls cell behavior via selective repetitive cell deformation based on a poroelastic cell model. The vibrating indentations induce repetitive water redistribution in the cells with water redistribution rates faster than the vibrating rate; however, in the opposite case, cells perceive the vibrations as a one-time stimulus. The selective regulation of cell-cell adhesion through adjusting the frequency of nanovibration was demonstrated by suppression of cadherin expression in smooth muscle cells (fast water redistribution rate) with no change in vascular endothelial cells (slow water redistribution rate). This technique may provide a new strategy for cell-type-specific mechanical stimulation.

Effects of dietary protein levels on performance, nitrogen excretion, and odor emission of growing pullets and laying hens.

The objective of this study was to determine the effects of dietary crude protein (CP) levels on production performance, nitrogen balance, and odor emission of excreta in growing pullets and laying hens from 13 to 32 wk of age. Two hundred and forty pullets (Hy-Line Brown) were randomly assigned to 1 of 4 dietary groups with 10 replicates per group, and 6 birds per replicate. Experimental diets were formulated to contain 4 graded CP levels in the diets of pullets ranging from 180, 160, 140, and 120 g/kg of diet during 13 to 18 wk (phase 1) and in the diets of laying hens from 190, 170, 150, and 130 g/kg of diet during 19 to 32 wk (phase 2). The limiting amino acids including lysine, methionine, and threonine were supplemented to maintain constant equal amino acid concentrations in all experiment diets. In phase 1, decreasing dietary CP levels did not affect growth performance but increased (linear and quadratic effect, P < 0.05) the relative abdominal fat contents and triglyceride concentration in serum samples. High-density lipoprotein cholesterol in serum samples decreased as the CP levels decreased in the diets of pullets. Dietary CP levels quadratically increased (P < 0.05) the villus height and the villus height to crypt depth ratio but did not affect tibia traits and relative organ weights in pullets at 18 wk. Apparent digestibility of dry matter and ether extract increased with decreasing dietary CP levels in pullets. Graded CP levels linearly increased the digestibility of dry matter, CP, and ether extracts but lowered that of crude ash in laying hens. Nitrogen excretion was linearly decreased (P < 0.05) as the dietary CP levels decreased in both pullets and laying hens. Dietary CP levels only affected carbon dioxide emission in pullets. In phase 2, dietary CP levels did not affect growth performance and the ages at first egg laying and to reach 50% egg production in laying hens. However, egg weights were decreased (linear and quadratic effect, P < 0.05) as the dietary CP level decreased in laying hens. Increasing dietary CP levels increased Haugh unit at 26 wk but lowered corticosterone concentrations in yolk samples at 22 wk. Collectively, this study shows that dietary CP levels could be decreased to reduce nitrogen excretion without adverse effects on performance and egg quality of growing pullets and laying hens.

Effect of Dietary Chlorella vulgaris or Tetradesmus obliquus on Laying Performance and Intestinal Immune Cell Parameters.

A feeding trial was conducted to investigate the effect of dietary supplementation of Chlorella vulgaris (CV) or Tetradesmus obliquus (TO) on laying performance, egg quality, and gut health indicators of laying hens. A total of 144 Hy-Line Brown laying hens aged 21 weeks were randomly assigned to one of three dietary treatments with eight replicates of six hens. Dietary treatments were as follows: CON, basal diet; CV, basal diet + 5 g C. vulgaris/kg of diet; TO, basal diet + 5 g T. obliquus/kg of diet. The results showed that diets supplemented with CV or TO had insignificant effects on laying performance, egg quality (i.e., Haugh unit and eggshell strength and thickness), jejunal histology, cecal short-chain fatty acids, and antioxidant/immune markers in ileal mucosa samples of laying hens. Compared with the control group, the egg yolk color score was higher (p < 0.05) in laying hens fed on diets containing CV and TO, although the former was a more intense yellow than the latter. Small intestinal lamina propria cells were isolated using flow cytometry to examine the percentages of immune cell subpopulations. Dietary microalgae did not affect B cells or monocytes/macrophages but altered the percentage of CD4+ T cells and CD8- TCR γδ T cells. Collectively, diets supplemented with C. vulgaris or T. obliquus can improve egg yolk color and would modulate host immune development and competence in laying hens.

A dual-regulation inducible switch system for microRNA detection and cell type-specific gene activation.

Rationale: MicroRNAs (miRNAs) play key roles in multiple biological processes, many of which exhibit distinct cell type-specific expression patterns. A miRNA-inducible expression system can be adapted as a signal-on reporter for detecting miRNA activity or as a cell type-specific gene activation tool. However, due to the inhibitory properties of miRNAs on gene expression, few miRNA-inducible expression systems are available, and the available systems are only transcriptional or post-transcriptional regulatory system with obvious leaky expression. Methods: To address this limitation, a miRNA-inducible expression system that can tightly control target gene expression is desirable. Here, by taking advantage of an enhanced LacI repression system and the translational repressor L7Ae, a miRNA-inducible dual transcriptional-translational switch system was designed called the miR-ON-D system. Luciferase activity assay, western blotting, CCK-8 assay and flow cytometry analysis were performed to characterize and validate this system. Results: The results demonstrated that leakage expression was strongly suppressed in the miR-ON-D system. It was also validated that the miR-ON-D system could be used to detect exogenous and endogenous miRNAs in mammalian cells. Moreover, it was shown that the miR-ON-D system could be triggered by cell type-specific miRNAs to regulate the expression of biologically relevant proteins (e.g., p21 and Bax) to achieve cell type-specific reprogramming. Conclusion: This study established a tight miRNA-inducible expression switch system for miRNA detection and cell type-specific gene activation.

Cinnamaldehyde-Rich Cinnamon Extract Induces Cell Death in Colon Cancer Cell Lines HCT 116 and HT-29.

Cinnamon is a natural spice with a wide range of pharmacological functions, including anti-microbial, antioxidant, and anti-tumor activities. The aim of this study is to investigate the effects of cinnamaldehyde-rich cinnamon extract (CRCE) on the colorectal cancer cell lines HCT 116 and HT-29. The gas chromatography mass spectrometry analysis of a lipophilic extract of cinnamon revealed the dominance of trans-cinnamaldehyde. Cells treated with CRCE (10-60 µg/mL) showed significantly decreased cell viability in a time- and dose-dependent manner. We also observed that cell proliferation and migration capacity were inhibited in CRCE-treated cells. In addition, a remarkable increase in the number of sub-G1-phase cells was observed with arrest at the G2 phase by CRCE treatment. CRCE also induced mitochondrial stress, and finally, CRCE treatment resulted in activation of apoptotic proteins Caspase-3, -9, and PARP and decreased levels of mu-2-related death-inducing gene protein expression with BH3-interacting domain death agonist (BID) activation.

Role of Dietary Methyl Sulfonyl Methane in Poultry.

Oxidative stress is defined as an imbalance between pro-oxidants and anti-oxidants within biological systems, leading to tissue damage and compromising the health of afflicted animals. The incorporation of dietary anti-oxidants into chicken diets has been a common practice to improve the performance, health, and welfare of the host by protecting against oxidative stress-induced damage. Methyl sulfonyl methane (MSM), a naturally occurring organosulfur compound found in various plant sources, has demonstrated various beneficial biological properties, including anti-inflammatory and anti-oxidant properties in both in vitro and in vivo studies. MSM has been utilized as a dietary supplement for humans for its anti-oxidant, analgesic, and anti-inflammatory properties. It has also been administered to domestic animals, including cattle, pigs, and chickens, owing to its recognized anti-oxidant effect. This review summarizes the biological and physiological functions of dietary MSM in poultry.

Covalent organic framework nanomedicines: Biocompatibility for advanced nanocarriers and cancer theranostics applications.

Nanomedicines for drug delivery and imaging-guided cancer therapy is a rapidly growing research area. The unique properties of nanomedicines have a massive potential in solving longstanding challenges of existing cancer drugs, such as poor localization at the tumor site, high drug doses and toxicity, recurrence, and poor immune response. However, inadequate biocompatibility restricts their potential in clinical translation. Therefore, advanced nanomaterials with high biocompatibility and enhanced therapeutic efficiency are highly desired to fast-track the clinical translation of nanomedicines. Intrinsic properties of nanoscale covalent organic frameworks (nCOFs), such as suitable size, modular pore geometry and porosity, and straightforward post-synthetic modification via simple organic transformations, make them incredibly attractive for future nanomedicines. The ability of COFs to disintegrate in a slightly acidic tumor microenvironment also gives them a competitive advantage in targeted delivery. This review summarizes recently published applications of COFs in drug delivery, photo-immuno therapy, sonodynamic therapy, photothermal therapy, chemotherapy, pyroptosis, and combination therapy. Herein we mainly focused on modifications of COFs to enhance their biocompatibility, efficacy and potential clinical translation. This review will provide the fundamental knowledge in designing biocompatible nCOFs-based nanomedicines and will help in the rapid development of cancer drug carriers and theranostics.

Biomimetic hydrogel blanket for conserving and recovering intrinsic cell properties.

BACKGROUND: Cells in the human body experience different growth environments and conditions, such as compressive pressure and oxygen concentrations, depending on the type and location of the tissue. Thus, a culture device that emulates the environment inside the body is required to study cells outside the body. METHODS: A blanket-type cell culture device (Direct Contact Pressing: DCP) was fabricated with an alginate-based hydrogel. Changes in cell morphology due to DCP pressure were observed using a phase contrast microscope. The changes in the oxygen permeability and pressure according to the hydrogel concentration of DCP were analyzed. To compare the effects of DCP with normal or artificial hypoxic cultures, cells were divided based on the culture technique: normal culture, DCP culture device, and artificial hypoxic environment. Changes in phenotype, genes, and glycosaminoglycan amounts according to each environment were evaluated. Based on this, the mechanism of each culture environment on the intrinsic properties of conserving chondrocytes was suggested. RESULTS: Chondrocytes live under pressure from the surrounding collagen tissue and experience a hypoxic environment because collagen inhibits oxygen permeability. By culturing the chondrocytes in a DCP environment, the capability of DCP to produce a low-oxygen and physical pressure environment was verified. When human primary chondrocytes, which require pressure and a low-oxygen environment during culture to maintain their innate properties, were cultured using the hydrogel blanket, the original shapes and properties of the chondrocytes were maintained. The intrinsic properties could be recovered even in aged cells that had lost their original cell properties. CONCLUSIONS: A DCP culture method using a biomimetic hydrogel blanket provides cells with an adjustable physical pressure and a low-oxygen environment. Through this technique, we could maintain the original cellular phenotypes and intrinsic properties of human primary chondrocytes. The results of this study can be applied to other cells that require special pressure and oxygen concentration control to maintain their intrinsic properties. Additionally, this technique has the potential to be applied to the re-differentiation of cells that have lost their original properties.

XAF1 drives apoptotic switch of endoplasmic reticulum stress response through destabilization of GRP78 and CHIP.

X-linked inhibitor of apoptosis-associated factor-1 (XAF1) is a stress-inducible tumor suppressor that is commonly inactivated in many human cancers. Despite accumulating evidence for the pro-apoptotic role for XAF1 under various stressful conditions, its involvement in endoplasmic reticulum (ER) stress response remains undefined. Here, we report that XAF1 increases cell sensitivity to ER stress and acts as a molecular switch in unfolded protein response (UPR)-mediated cell-fate decisions favoring apoptosis over adaptive autophagy. Mechanistically, XAF1 interacts with and destabilizes ER stress sensor GRP78 through the assembly of zinc finger protein 313 (ZNF313)-mediated destruction complex. Moreover, XAF1 expression is activated through PERK-Nrf2 signaling and destabilizes C-terminus of Hsc70-interacting protein (CHIP) ubiquitin E3 ligase, thereby blocking CHIP-mediated K63-linked ubiquitination and subsequent phosphorylation of inositol-required enzyme-1α (IRE1α) that is involved in in the adaptive ER stress response. In tumor xenograft assays, XAF1-/- tumors display substantially lower regression compared to XAF1+/+ tumors in response to cytotoxic dose of ER stress inducer. XAF1 and GRP78 expression show an inverse correlation in human cancer cell lines and primary breast carcinomas. Collectively this study uncovers an important role for XAF1 as a linchpin to govern the sensitivity to ER stress and the outcomes of UPR signaling, illuminating the mechanistic consequence of XAF1 inactivation in tumorigenesis.