Lung and Cutaneous Abscesses in a Patient with Ulcerative Colitis: A Case Report and Literature Review.

Aseptic abscess (AA) syndrome is a rare inflammatory disorder often associated with inflammatory bowel disease (IBD). Cases of IBD-associated AA have been reported in Japan, India, and Canada, but rarely in China. Herein, we present the case of a Chinese patient with IBD-associated AAs and review the literature on AA with underlying IBD. We report the case of a 48-year-old male patient with multiple AAs on his left hand and lungs who was successfully treated with prednisone. He had undergone cutaneous abscess incision and drainage twice in the previous 2 years. The patient presented to our hospital with ulcerative colitis and pain in the dorsum of the left hand. Pus from his hand and blood cultures revealed sterile cutaneous abscesses. Chest computed tomography examination during hospitalization revealed a lung abscess. The AA was unresponsive to cefotiam or cefoperazone-sulbactam. The patient's left hand and lung conditions did not improve until prednisone was administered. The patient was followed up as an outpatient for 3 months and recovered without any clinical symptoms. We retrieved 17 cases of IBD-associated AA from the literature. None of the patients showed evidence of infection and failed antibiotic treatment, and all improved with corticosteroid use. AA may be an extra-intestinal manifestation of IBD. Effective medications include corticosteroids and immunosuppressive agents. This case may increase the awareness of AA and aid in early identification.

An acid-tolerant metal-organic framework for industrial CO2 electrolysis using a proton exchange membrane.

Industrial CO2 electrolysis via electrochemical CO2 reduction has achieved progress in alkaline solutions, while the same reaction in acidic solution remains challenging because of severe hydrogen evolution side reactions, acid corrosion, and low target product selectivity. Herein, an industrial acidic CO2 electrolysis to pure HCOOH system is realized in a proton-exchange-membrane electrolyzer using an acid-tolerant Bi-based metal-organic framework guided by a Pourbaix diagram. Significantly, the Faradaic efficiency of HCOOH synthesis reaches 95.10% at a large current density of 400 mA/cm2 with a high CO2 single-pass conversion efficiency of 64.91%. Moreover, the proton-exchange-membrane device also achieves an industrial-level current density of 250 mA/cm2 under a relatively low voltage of 3.5 V for up to 100 h with a Faradaic efficiency of 93.5% for HCOOH production, which corresponds to an energy consumption of 200.65 kWh/kmol, production rate of 12.1 mmol/m2/s, and an energy conversion efficiency of 38.2%. These results will greatly aid the contemporary research moving toward commercial implementation and success of CO2 electrolysis technology.

Metal ions steer the duality in microbial community recovery from nitrogen enrichment by shaping functional groups.

Atmospheric nitrogen (N) deposition has been substantially reduced due to declines in the reactive N emission in major regions of the world. Nevertheless, the impact of reduced N deposition on soil microbial communities and the mechanisms by which they are regulated remain largely unknown. Here, we examined the effects of N addition and cessation of N addition on plant and soil microbial communities through a 17-year field experiment in a temperate grassland. We found that extreme N input did not irreversibly disrupt the ecosystem, but ceasing high levels of N addition led to greater resilience in bacterial and fungal communities. Fungi exhibited diminished resilience compared to bacteria due to their heightened reliance on changes in plant communities. Neither bacterial nor fungal diversity fully recovered to their original states. Their sensitivity and resilience were mainly steered by toxic metal ions and soil pH differentially regulating on functional taxa. Specifically, beneficial symbiotic microbes such as N-fixing bacteria and arbuscular mycorrhizal fungi experienced detrimental effects from toxic metal ions and lower pH, hindering their recovery. The bacterial functional groups involved in carbon decomposition, and ericoid mycorrhizal and saprotrophic fungi were positively influenced by soil metals, and demonstrated gradual recovery. These findings could advance our mechanistic understanding of microbial community dynamics under ongoing global changes, thereby informing management strategies to mitigate the adverse effects of N enrichment on soil function.

Asymmetric Mannich/Cyclization Reaction of 2-Benzothiazolimines and 2-Isothiocyano-1-indanones to Construct Chiral Spirocyclic Compounds.

An efficient and practical organocatalyzed asymmetric Mannich/cyclization tandem reaction strategy of 2-benzothiazolimines and 2-isothiocyanato-1-indanones was developed, and novel spirocyclic compounds containing benzothiazolimine and indanone scaffolds were obtained. This chiral thiourea-catalyzed Mannich/cyclization tandem reaction offers chiral spirocyclic compounds with continuous tertiary and quaternary stereocenters in good to high yields (up to 90%) with excellent diastereoselectivities (up to >20:1 dr) and enantioselectivities (up to 98% ee) at -18 °C. Additionally, the scaled-up synthesis was also performed with retained yield and stereoselectivity, and a reaction mechanism was also proposed.

Crosstalk between Circadian Rhythm Dysregulation and Tumorigenesis, Tumor Metabolism and Tumor Immune Response.

Circadian rhythm is a self-regulating 24-hour system that synchronizes with the day and night cycle in organisms. The regulation of this system is controlled by clock genes, which function to harmoniously express molecular levels that facilitate the orderly coordination of various cellular processes, such as sleep, metabolism, endocrine function, cell proliferation and immunity. The root cause of tumorigenesis is that the body loses its normal regulation of cell growth at the genetic level. Long-term disruptions in circadian rhythms caused by factors such as shift work, jet lag, and unstable sleep patterns can impact cellular health, leading to various health problems, including cancer. Circadian rhythm controls most cellular functions related to cancer progression, which has a significant impact on the ability of immune cells to detect cancer cells and promote their clearance and has crucial implication for future tumor immunotherapy. This article aims to review the crosstalk between dysregulation of circadian rhythm and tumorigenesis, tumor metabolism, and immune response. Additionally, we discuss the role of circadian rhythm disruption in tumor therapy, highlighting its potential to optimize treatment timing and improve therapeutic outcomes.

14-3-3 Family of Proteins: Biological Implications, Molecular Interactions, and Potential Intervention in Cancer, Virus and Neurodegeneration Disorders.

The 14-3-3 family of proteins are highly conserved acidic eukaryotic proteins (25-32 kDa) abundantly present in the body. Through numerous binding partners, the 14-3-3 is responsible for many essential cellular pathways, such as cell cycle regulation and gene transcription control. Hence, its dysregulation has been linked to the onset of critical illnesses such as cancers, neurodegenerative diseases and viral infections. Interestingly, explorative studies have revealed an inverse correlation of 14-3-3 protein in cancer and neurodegenerative diseases, and the direct manipulation of 14-3-3 by virus to enhance infection capacity has dramatically extended its significance. Of these, COVID-19 has been linked to the 14-3-3 proteins by the interference of the SARS-CoV-2 nucleocapsid (N) protein during virion assembly. Given its predisposition towards multiple essential host signalling pathways, it is vital to understand the holistic interactions between the 14-3-3 protein to unravel its potential therapeutic unit in the future. As such, the general structure and properties of the 14-3-3 family of proteins, as well as their known biological functions and implications in cancer, neurodegeneration, and viruses, were covered in this review. Furthermore, the potential therapeutic target of 14-3-3 proteins in the associated diseases was discussed.

Identifying suitable candidates for pancreaticoduodenectomy with extended lymphadenectomy for pancreatic ductal adenocarcinoma.

BACKGROUND: To evaluate long-term quality of life and survival in pancreatic ductal adenocarcinoma (PDAC) patients after pancreatoduodenectomy with extended lymphadenectomy (PDEL) and identify candidates. METHODS: Patients with resectable PDAC with ≥1 examined lymph node (LN) during pancreatoduodenectomy (PD), and were divided into the PD with standard lymphadenectomy (PDSL) and PDEL groups. Perioperative data, long-term quality of life and survival were compared, and the prognostic effect of LNs ± in every peripancreatic station were analysed. RESULTS: Screening 446 PDAC patients, 237 and 126 were included in the PDSL and PDEL groups, respectively. The PDEL group showed a longer operation time, greater intraoperative blood loss, severe diarrhoea, a higher incidence of grade III complications. Notably, the PDEL patients experienced significant relief from low back pain and diarrhoea, with an obvious survival advantage (p = 0.037), especially in patients with preoperative tumor contact with vascular and pathological N0; however, LNs+ in any station (No. 8p, 12, 14, or 16) were associated with a poorer prognosis. The vascular reconstruction, T and N stage were independent risk factors for survival. CONCLUSION: PDEL can relieve symptoms and prolong the survival of PDAC patients with acceptable complications, and EL should be performed regardless of preoperative LN enlargement.

Hybrid YOLOv3 and ReID intelligent identification statistical model for people flow in public places.

The statistical model for automatic flow recognition is significant for public place management. However, the current model suffers from insufficient statistical accuracy and low lightweight. Therefore, in this study, the structure of the lightweight object detection model "You Only Live Once v3" is optimized, and the "Deep Simple Online Real-Time Tracking" algorithm with the "Person Re-Identification" module is designed, so as to construct a statistical model for people flow recognition. The results showed that the median PersonAP of the designed model was 94.2%, the total detection time was 216 ms, the Rank-1 and Rank-10 were 87.2% and 98.6%, respectively, and the maximum occupied memory of the whole test set was 2.57 MB, which was better than all comparison models. The results indicate that the intelligent identification statistical model for public crowd flow obtained through this design and training has higher statistical accuracy, less computational resource consumption, and faster computing speed. This has certain application space in the management and guidance of crowd flow in public places.

Prevention of the Quality Degradation of Antarctic Krill (Euphausia superba) Meal through Two-Stage Drying.

To achieve a krill meal of high quality, a two-stage drying involving hot-air drying and vacuum drying was investigated. Five experimental groups were established according to the different drying conditions in the second stage, including 95 °C and 101 kPa, 95 °C and 60 kPa, 75 °C and 101 kPa, 75 °C and 60 kPa, and 75 °C and 20 kPa. The results showed that reducing the drying temperature and vacuum pressure in the second stage had a significant impact on the drying characteristics, sensory quality, and bioactive compounds of krill meal. Among all five groups, the drying condition of 75 °C and 60 kPa maintained a high drying rate while preserving a phospholipid content of 30.01 mg/kg and an astaxanthin content of 37.41 mg/kg. It also effectively reduced the isomerization of astaxanthin and the oxidation of unsaturated fatty acids. These results suggested that the two-stage drying method may contribute to the production of high-quality krill meal.

Latinx adolescents' daily family assistance and emotional well-being before and amid the COVID-19 pandemic: A pilot measurement burst study.

This study examined Latinx adolescents' daily family assistance (assistance day, assistance time, language brokering) in relation to their daily affect and investigated whether the associations changed following the outbreak of the COVID-19 pandemic. Two waves of 14-day daily diary data collected from 13 18-year-old Latinx adolescents (ndays = 284; 77% Mexican American, 77% female) before and amid the pandemic were analyzed using multilevel modeling. Three main findings emerged: (1) assisting the family on a given day was associated with higher levels of same-day positive affect both before and during COVID-19, and with lower levels of negative affect during COVID-19; (2) longer than usual family assistance time was associated with higher levels of same-day positive affect and lower levels of negative affect only during COVID-19; (3) language brokering on a given day was associated with higher levels of same-day positive affect both before and during COVID-19. These findings suggest a positive link between daily family assistance and Latinx youth's daily emotional well-being, particularly during the COVID-19 pandemic.

Occupancy Estimation from Blurred Video: A Multifaceted Approach with Privacy Consideration.

Building occupancy information is significant for a variety of reasons, from allocation of resources in smart buildings to responding during emergency situations. As most people spend more than 90% of their time indoors, a comfortable indoor environment is crucial. To ensure comfort, traditional HVAC systems condition rooms assuming maximum occupancy, accounting for more than 50% of buildings' energy budgets in the US. Occupancy level is a key factor in ensuring energy efficiency, as occupancy-controlled HVAC systems can reduce energy waste by conditioning rooms based on actual usage. Numerous studies have focused on developing occupancy estimation models leveraging existing sensors, with camera-based methods gaining popularity due to their high precision and widespread availability. However, the main concern with using cameras for occupancy estimation is the potential violation of occupants' privacy. Unlike previous video-/image-based occupancy estimation methods, we addressed the issue of occupants' privacy in this work by proposing and investigating both motion-based and motion-independent occupancy counting methods on intentionally blurred video frames. Our proposed approach included the development of a motion-based technique that inherently preserves privacy, as well as motion-independent techniques such as detection-based and density-estimation-based methods. To improve the accuracy of the motion-independent approaches, we utilized deblurring methods: an iterative statistical technique and a deep-learning-based method. Furthermore, we conducted an analysis of the privacy implications of our motion-independent occupancy counting system by comparing the original, blurred, and deblurred frames using different image quality assessment metrics. This analysis provided insights into the trade-off between occupancy estimation accuracy and the preservation of occupants' visual privacy. The combination of iterative statistical deblurring and density estimation achieved a 16.29% counting error, outperforming our other proposed approaches while preserving occupants' visual privacy to a certain extent. Our multifaceted approach aims to contribute to the field of occupancy estimation by proposing a solution that seeks to balance the trade-off between accuracy and privacy. While further research is needed to fully address this complex issue, our work provides insights and a step towards a more privacy-aware occupancy estimation system.

Screening and genetic engineering of marine-derived Aspergillus terreus for high-efficient production of lovastatin.

BACKGROUND: Lovastatin has widespread applications thanks to its multiple pharmacological effects. Fermentation by filamentous fungi represents the major way of lovastatin production. However, the current lovastatin productivity by fungal fermentation is limited and needs to be improved. RESULTS: In this study, the lovastatin-producing strains of Aspergillus terreus from marine environment were screened, and their lovastatin productions were further improved by genetic engineering. Five strains of A. terreus were isolated from various marine environments. Their secondary metabolites were profiled by metabolomics analysis using Ultra Performance Liquid Chromatography-Mass spectrometry (UPLC-MS) with Global Natural Products Social Molecular Networking (GNPS), revealing that the production of secondary metabolites was variable among different strains. Remarkably, the strain of A. terreus MJ106 could principally biosynthesize the target drug lovastatin, which was confirmed by High Performance Liquid Chromatography (HPLC) and gene expression analysis. By one-factor experiment, lactose was found to be the best carbon source for A. terreus MJ106 to produce lovastatin. To improve the lovastatin titer in A. terreus MJ106, genetic engineering was applied to this strain. Firstly, a series of strong promoters was identified by transcriptomic and green fluorescent protein reporter analysis. Then, three selected strong promoters were used to overexpress the transcription factor gene lovE encoding the major transactivator for lov gene cluster expression. The results revealed that compared to A. terreus MJ106, all lovE over-expression mutants exhibited significantly more production of lovastatin and higher gene expression. One of them, LovE-b19, showed the highest lovastatin productivity at a titer of 1512 mg/L, which represents the highest production level reported in A. terreus. CONCLUSION: Our data suggested that combination of strain screen and genetic engineering represents a powerful tool for improving the productivity of fungal secondary metabolites, which could be adopted for large-scale production of lovastatin in marine-derived A. terreus.

Evaluating stress and displacement in the craniomandibular complex using Twin Block appliances at varied angles: A finite element study.

OBJECTIVES: The objective of this investigation was to assess the stress and displacement pattern of the craniomandibular complex by employing finite element methodology to simulate diverse angulations of inclined planes that are incorporated in the Twin Block appliance. METHODS: A 3D finite element representation was established by use of Cone Beam Computed Tomography (CBCT) scans. This comprehensive structure included craniofacial skeletal components, the articular disc, a posterior disc elastic layer, dental elements, periodontal ligaments, and a Twin Block appliance. This investigation is the first to incorporated inclined planes featuring three distinct angulations (45, 60, and 70°) as the study models. Mechanical impacts were evaluated within the glenoid fossa, tooth, condylar, and articular disc regions. RESULTS: In all simulations, the stress generated by the Twin Block appliance was distributed across teeth and periodontal ligament, facilitating the anterior movement of mandibular teeth and the posterior displacement of maxillary teeth. Within the temporomandibular joint region, compressive forces on the superior and posterior facets of the condyle diminished, coinciding with the stress configuration that fosters condylar and mandibular growth. Stress dispersion homogenized in the condylar anterior facet and articular disc, with considerable tensile stress in the glenoid fossa's posterior aspect conforming to stress distribution that promote fossa reconfiguration. The 70° inclined plane exerts the highest force on the tissues. The condyle's maximum and minimum principal stresses are 0.36 MPa and -0.15 MPa, respectively, while those of the glenoid fossa are 0.54 MPa and -0.23 MPa. CONCLUSION: Three angled appliances serve the purpose of advancing the mandible. A 45° inclined plane relative to the occlusal plane exerts balanced anteroposterior and vertical forces on the mandibular arch. Steeper angles yield greater horizontal forces, which may enhance forward growth and efficient repositioning.

Establishment and evaluation of a prognostic model for patients with unresectable gastric cancer liver metastases.

BACKGROUND: Liver metastases (LM) is the primary factor contributing to unfavorable outcomes in patients diagnosed with gastric cancer (GC). The objective of this study is to analyze significant prognostic risk factors for patients with GCLM and develop a reliable nomogram model that can accurately predict individualized prognosis, thereby enhancing the ability to evaluate patient outcomes. AIM: To analyze prognostic risk factors for GCLM and develop a reliable nomogram model to accurately predict individualized prognosis, thereby enhancing patient outcome assessment. METHODS: Retrospective analysis was conducted on clinical data pertaining to GCLM (type III), admitted to the Department of General Surgery across multiple centers of the Chinese PLA General Hospital from January 2010 to January 2018. The dataset was divided into a development cohort and validation cohort in a ratio of 2:1. In the development cohort, we utilized univariate and multivariate Cox regression analyses to identify independent risk factors associated with overall survival in GCLM patients. Subsequently, we established a prediction model based on these findings and evaluated its performance using receiver operator characteristic curve analysis, calibration curves, and clinical decision curves. A nomogram was created to visually represent the prediction model, which was then externally validated using the validation cohort. RESULTS: A total of 372 patients were included in this study, comprising 248 individuals in the development cohort and 124 individuals in the validation cohort. Based on Cox analysis results, our final prediction model incorporated five independent risk factors including albumin levels, primary tumor size, presence of extrahepatic metastases, surgical treatment status, and chemotherapy administration. The 1-, 3-, and 5-years Area Under the Curve values in the development cohort are 0.753, 0.859, and 0.909, respectively; whereas in the validation cohort, they are observed to be 0.772, 0.848, and 0.923. Furthermore, the calibration curves demonstrated excellent consistency between observed values and actual values. Finally, the decision curve analysis curve indicated substantial net clinical benefit. CONCLUSION: Our study identified significant prognostic risk factors for GCLM and developed a reliable nomogram model, demonstrating promising predictive accuracy and potential clinical benefit in evaluating patient outcomes.

[Research progress in the regulation of autophagy and mitochondrial homeostasis by AMPK signaling channels].

AMP-activated protein kinase (AMPK) is a widely distributed and evolutionarily conserved serine/threonine protein kinase present in eukaryotic cells. In regulating cellular energy metabolism, AMPK plays an extremely important role as an energy metabolic kinase. When the body is in a low energy state, AMPK is activated in response to changes in intracellular adenine nucleotide levels and is bound to adenosine monophosphate (AMP) or adenosine diphosphate (ADP). Activated AMPK regulates various metabolic processes, including lipid and glucose metabolism and cellular autophagy. AMPK directly promotes autophagy by phosphorylating autophagy-related proteins in the mammalian target of rapamycin complex 1 (mTORC1), serine/threonine protein kinase-dysregulated 51-like kinase 1 (ULK1) and type III phosphatidylinositol 3-kinase-vacuolar protein-sorting 34 (PIK3C3-VPS34) complexes. AMPK also indirectly promotes autophagy by regulating the expression of downstream autophagy-related genes of transcription factors such as forkhead box O3 (FOXO3), lysosomal function transcription factor EB (TFEB) and bromodomain protein 4 (BRD4). AMPK also regulates mitochondrial autophagy, induces the division of damaged mitochondria and promotes the transfer of the autophagic response to damaged mitochondria. Another function of AMPK is to regulate mitochondrial health by stimulating mitochondrial biogenesis and participating in various aspects of mitochondrial homeostasis regulation. This review discusses the specific regulation of mitochondrial biology and internal environmental homeostasis by AMPK signaling channels as central to the cellular response to energy stress and regulation of mitochondria, highlighting the key role of AMPK in regulating cellular autophagy and mitochondrial autophagy, as well as advances in research on the regulation of mitochondrial homeostasis.

Embracing the hidden potential: The contribution of majority world research to developmental science.

Research on adolescence from the Majority World possesses major hidden potential in contributing to global adolescent research and developmental science more broadly. In this commentary, the authors (1) describe the background and the process through which this special issue came into fruition, (2) introduce the emic approaches to study the influences of macro-contextual variations on developmental science and provide several pertinent examples on the contributions of Majority World research, (3) elaborate on challenges and barriers that Majority World scholars often face in conducting and disseminating their research, and (4) a few actionable steps and recommendations in promoting the representation and inclusion of Majority World research into global developmental science. Only when our field fully integrates findings from all regions of the world will we be able to develop a fundamental scientific representation and understanding of what it means to be an adolescent, how adolescents develop over time, and what tasks or phenomena in adolescent development are truly universal or specific to particular groups, regions, or areas.

Electrocatalytic Acetylene Hydrogenation in Concentrated Seawater at Industrial Current Densities.

Electrocatalytic acetylene hydrogenation to ethylene (E-AHE) is a promising alternative for thermal-catalytic process, yet it suffers from low current densities and efficiency. Here, we achieved a 71.2 % Faradaic efficiency (FE) of E-AHE at a large partial current density of 1.0 A cm-2 using concentrated seawater as an electrolyte, which can be recycled from the brine waste (0.96 M NaCl) of alkaline seawater electrolysis (ASE). Mechanistic studies unveiled that cation of concentrated seawater dynamically prompted unsaturated interfacial water dissociation to provide protons for enhanced E-AHE. As a result, compared with freshwater, a twofold increase of FE of E-AHE was achieved on concentrated seawater-based electrolysis. We also demonstrated an integrated system of ASE and E-AHE for hydrogen and ethylene production, in which the obtained brine output from ASE was directly fed into E-AHE process without any further treatment for continuously cyclic operations. This innovative system delivered outstanding FE and selectivity of ethylene surpassed 97.0 % and 97.5 % across wide-industrial current density range (≤ 0.6 A cm-2), respectively. This work provides a significant advance of electrocatalytic ethylene production coupling with brine refining of seawater electrolysis.

Changes in the Quality and Microbial Communities of Precooked Seasoned Crayfish Tail Treated with Microwave and Biological Preservatives during Room Temperature Storage.

The qualities of precooked foods can be significantly changed by the microorganisms produced during room temperature storage. This work assessed the effects of different antibacterial treatments (CK, without any treatment; microwave treatment, MS; microwave treatment and biological preservatives, MSBP) on the physicochemical properties and microbial communities of precooked crayfish tails during room temperature storage. Only the combination of microwave sterilization and biological preservatives significantly inhibited spoilage, as evidenced by the total viable count (4.15 log CFU/g) after 3 days of room temperature storage, which satisfied the transit time of most logistics companies in China. Changes in pH and TVB-N were also significantly inhibited in the MSBP group compared with those in the CK and MS groups. More than 30 new volatile compounds were produced in the CK groups during room temperature storage. However, in the MSBP groups, the volatile compounds were almost unchanged. The correlations between the microbial composition and volatile compounds suggested that specific bacterial species with metabolic activities related to amino acid, energy, cofactor, and vitamin metabolism, as well as xenobiotics biodegradation and metabolism, were responsible for the changes in volatile compounds. These bacteria included Psychrobacter, Arthrobacter, Facklamia, Leucobacter, Corynebacterium, Erysipelothrix, Devosia, Dietzia, and Acidovorax. Overall, our findings provide a foundation for the development of strategies to inhibit spoilage in precooked crayfish tails stored at room temperature.

Dynamic Structures and Fast Transition Kinetics of Oxidized G-Quadruplexes.

8-oxoguanines (8-oxoG) in cells form compromised G-quadruplexes (GQs), which may vary GQ mediated gene regulations. By mimicking molecularly crowded cellular environment using 40% DMSO or sucrose, here it is found that oxidized human telomeric GQs have stabilities close to the wild-type (WT) GQs. Surprisingly, while WT GQs show negative formation cooperativity between a Pt(II) binder and molecularly crowded environment, positive cooperativity is observed for oxidized GQ formation. Single-molecule mechanical unfolding reveals that 8-oxoG sequence formed more diverse and flexible structures with faster folding/unfolding transition kinetics, which facilitates the Pt(II) ligand to bind the best-fit structures with positive cooperativity. These findings offer new understanding on structures and properties of oxidized G-rich species in crowded environments. They also provide insights into the design of better ligands to target oxidized G-rich structures formed under oxidative cell stress.