Cuproptosis and Cuproptosis-Based Synergistic Therapy for Cancer Treatment.

Copper, as an essential trace nutrient for human, plays a crucial role in numerous cellular activities, and is vital for maintaining homeostasis in organisms. Deviations from normal intracellular copper concentration range can disrupt the cellular homeostasis and lead to cell death. Cell death is the process in which cells lose their vitality and cannot sustain normal metabolism, which has various forms. The recently discovered cuproptosis mechanism differs from the previously recognized forms, which is triggered by intracellular copper accumulation. The discovery of cuproptosis has sparked interest among researchers, and this mechanism has been applied in the treatment of various intractable diseases, including different types of cancer. However, the developed cuproptosis-based therapies have revealed certain limitations, such as low immunostimulatory efficiency, poor tumor targeting, and inhibition by the tumor microenvironment. Therefore, researchers are devoted to combining cuproptosis with existing cancer therapies to develop more effective synergistic cancer therapies. This review summarizes the latest research advancements in the cuproptosis-based therapies for various types of cancer, with a focus on the synergistic cancer therapies. Finally, it provides an outlook on the future development of cuproptosis in anti-tumor therapy.

Comprehensive evaluation of the water-fertilizer coupling effects on pumpkin under different irrigation volumes.

Compared to conventional irrigation and fertilization, the Water-fertilizer coupling can significantly enhance the efficiency of water and fertilizer utilization, thereby promoting crop growth and increasing yield. Targeting the challenges of poor crop growth, low yield, and inefficient water and fertilizer utilization in the arid region of northwest China under conventional irrigation and fertilization practices. Therefore, a two-year on-farm experiment in 2022 and 2023 was conducted to study the effects of water-fertilizer coupling regulation on pumpkin growth, yield, water consumption (ET), and water and fertilizer use efficiency. Simultaneously the comprehensive evaluation of multiple objectives was carried out using principal component analysis (PCA) methods, so as to propose an suitable water-fertilizer coupling regulation scheme for the region. The experiment was set up as a two-factor trial using water-fertilizer integration technology under three irrigation volume (W1 = 37.5 mm, W2 = 45.5 mm, W3 = 52.5mm) and three organic fertilizer application amounts (F1 = 3900-300 kg ha-1, F2 = 4800-450 kg·ha-1, F3 = 5700-600 kg·ha-1), with the traditional irrigation and fertilization scheme from local farmers as control treatments (CK). The results indicated that irrigation volume and organic fertilizer application significantly affected pumpkin growth, yield, and water and fertilizer use efficiency (P<0.05). Pumpkin yield increased with increasing irrigation volume. Increasing organic fertilizer levels within a certain range benefited pumpkin plant growth, dry matter accumulation, and yield, however, excessive application beyond a certain level had inhibited effects on those. The increased fertilizer application under the same irrigation volume enhanced the efficiency of water and fertilizer utilization. However excessive irrigation only resulted in inefficient water consumption, reducing the water and fertilizer use efficiency. The Comprehensive evaluation by PCA revealed that the F2W3 treatment outperformed all the others, effectively addressing the triple objectives of increasing production, improving efficiency, and promoting green production. Therefore, F2W3 (Irrigation volume: 52.5 mm; Fertilizer application amounts: 4800-450 kg/ha-1) as a water and fertilizer management scheme for efficient pumpkin production in the arid region of northwest China.

Excellent Pd-Loaded Magnetic Nanocatalyst on Multicarboxyl and Boronic Acid Biligands.

An effective palladium nanocatalyst (Fe3O4@SiO2-FPBA-DTPA-Pd) was proposed and prepared, which was immobilized on magnetic silica with ethylenediamine pentaacetic acid and formylphenylboronic acid as biligands. A series of characterizations showed that Fe3O4@SiO2-FPBA-DTPA-Pd was 5-15 nm and contained 1.44 mmol/g Pd2+/Pd0. It was stable below 232.7 °C, and its saturation magnetization value was 21.17 emu/g which was easily recycled by a magnet. Its catalytic ability was evaluated through 7 Suzuki reactions and 15 Heck reactions. Results showed that the yields of 14 reactions catalyzed by Fe3O4@SiO2-FPBA-DTPA-Pd were more than 90%, while were better than those of the other two immobilized Pd catalysts on a single diethyltriamine pentaacetic acid (DTPA) group or boronic acid group. Moreover, Fe3O4@SiO2-FPBA-DTPA-Pd showed good reusability in both Suzuki and Heck reactions. In two model Suzuki and Heck reactions, after seven cycles, its yields were still above 95% without significant loss, which exceeded those of many reported catalysts; therefore, it has great potential in future large-scale industrial production.

Sex-Specific Effects of Polystyrene Microplastic and Lead(II) Co-Exposure on the Gut Microbiome and Fecal Metabolome in C57BL/6 Mice.

The wide spread of microplastics has fueled growing public health concern globally. Due to their porous structure and large surface area, microplastics can serve as carriers for other environmental pollutants, including heavy metals. Although the toxic effects of microplastics or heavy metals have been reported previously, investigations into the sex-differential health effects of combined exposure to microplastics and heavy metals are lacking. In the present study, the effects of polystyrene microplastics and lead(II) co-exposure on the gut microbiome, intestinal permeability, and fecal metabolome were examined in both male and female mice. Combined exposure of polystyrene microplastics and lead(II) increased intestinal permeability in both male and female mice. Sex-specific responses to the co-exposure were found in gut bacteria, fungi, microbial metabolic pathways, microbial genes encoding antibiotic resistance and virulence factors, as well as fecal metabolic profiles. In particular, Shannon and Simpson indices of gut bacteria were reduced by the co-exposure only in female mice. A total of 34 and 13 fecal metabolites were altered in the co-exposure group in female and male mice, respectively, among which only three metabolites were shared by both sexes. These sex-specific responses to the co-exposure need to be taken into consideration when investigating the combined toxic effects of microplastics and heavy metals on the gut microbiota.

Protective effect of avicularin against lung cancer via inhibiting inflammation, oxidative stress, and induction of apoptosis: an in vitro and in vivo study.

The purpose of this research was to investigate whether or not avicularin (AVL) possesses any anticancer properties when tested against lung cancer. In the beginning, the effect that it had on the cellular viability of A549 cells was investigated, and it was discovered that AVL has a considerable negative impact on cellular viability. Following that, an investigation using flow cytometry was carried out to investigate its function in the process of apoptosis and the cell cycle of A549 cells. It has been discovered that AVL significantly promotes apoptosis and stops the cell cycle at the G2/M phase. The colony-forming capacity of A549 cells was observed to be greatly suppressed as the AVL concentration increased compared to the group that received no treatment. In addition to this, the benzo(a)pyrene in vivo model was established in order to investigate the pharmacological value of AVL. The findings revealed that AVL greatly prevented the formation of pro-inflammatory cytokines, in addition to the reduction in oxidative stress, which was evidenced by a reduction in the concentration of TNF-α, IL-1ß, IL-6, and MDA with an improvement in the concentration of SOD and GPx, respectively. Our results successfully demonstrated the pharmacological benefit of avicularin against lung cancer, and it has been suggested that it showed a multifactorial effect.

Bi2Te3 nanosheets promoted Pd for ethylene glycol electrooxidation both in the dark and under visible light irradiation.

Ethylene glycol electrooxidation catalyzed by Pd nanoparticles was found to be largely improved by Bi2Te3 nanosheets both in the dark and under visible light irradiation.

Differences in resting-state brain activity in first-episode drug-naïve major depressive disorder patients with and without suicidal ideation.

Despite altered brain activities being associated with suicidal ideation (SI), the neural correlates of SI in major depressive disorder (MDD) have remained elusive. We enrolled 82 first-episode drug-naïve MDD patients including 41 with SI and 41 without SI, as well as 41 healthy controls (HCs). Resting-state functional and structural MRI data were collected. The measures of fractional amplitude of low-frequency fluctuation (fALFF) and grey matter volume (GMV) were calculated and compared. Compared with HCs, patients with SI exhibited increased fALFF values in the right rectus gyrus and left medial superior frontal gyrus, middle frontal gyrus and precuneus. Decreased GMV in the right parahippocampal gyrus, insula and middle occipital gyrus and increased GMV in the left superior frontal gyrus were detected in patients with SI. In addition, patients without SI demonstrated increased fALFF values in the right superior frontal gyrus and decreased fALFF values in the right postcentral gyrus. Decreased GMV in the left superior frontal gyrus, right medial superior frontal gyrus, opercular part of inferior frontal gyrus, postcentral gyrus, fusiform gyrus and increased left supplementary motor area, superior occipital gyrus, right anterior cingulate gyrus and superior temporal gyrus were revealed in patients with SI. Moreover, in comparison with patients without SI, increased fALFF values were identified in the left precuneus of patients with SI. However, no significant differences were found in GMV between patients with and without SI. These findings might be helpful for finding neuroimaging markers predicting individual suicide risk and detecting targeted brain regions for effective early interventions.

Diagnostic significance and potential function of miR-320d in schizophrenia.

OBJECTIVES: Schizophrenia is a chronic brain disorder and needs objective diagnostic biomarkers. MicroRNAs are highly expressed in the nervous system. The study investigated the expression and clinical values of serum miR-320d in schizophrenia patients. In addition, the underlying mechanism was preliminarily examined via bioinformatic analysis. MATERIALS AND METHODS: Serum samples were collected from 57 patients with first-episode schizophrenia and 62 healthy controls. The cognitive function of patients was assessed via Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB) consisting of seven domains. Serum miR-320d levels were tested via qRT-PCR. The miRNA target predictions were obtained from Target Scan, and annotated through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. RESULTS: Based on the GSE167630 dataset, downregulated serum miR-320d in schizophrenia was identified, which was determined in the serum of schizophrenia patients. Serum miR-320d presented a conspicuous relationship with MCCB score in both the control group and the schizophrenia group. After adjusting for age, sex, BMI, and education, serum miR-320d was still independently related to the occurrence of schizophrenia. It can identify schizophrenia cases from healthy ones with an AUC of 0.931. The Go enrichment analysis indicated that the target genes were mainly enriched in homophilic cell adhesion and cell-cell adhesion via plasma-membrane adhesion molecules, and GTPase activity and guanosine diphosphate (GDP) binding. Rap1 signaling pathway was enriched via KEGG analysis. CONCLUSION: Serum miR-320d can be taken as a candidate marker for the diagnosis of schizophrenia. Its regulatory role in neuronal cell adhesion and Rap1 signaling pathway might be the potential underlying mechanism of miR-320d in schizophrenia.

Aerobic Exercise Attenuates Pressure Overload-Induced Myocardial Remodeling and Myocardial Inflammation via Upregulating miR-574-3p in Mice.

BACKGROUND: Exercise training can promote cardiac rehabilitation, thereby reducing cardiovascular disease mortality and hospitalization rates. MicroRNAs (miRs) are closely related to heart disease, among which miR-574-3p plays an important role in myocardial remodeling, but its role in exercise-mediated cardioprotection is still unclear. METHODS: A mouse myocardial hypertrophy model was established by transverse aortic coarctation, and a 4-week swimming exercise training was performed 1 week after the operation. After swimming training, echocardiography was used to evaluate cardiac function in mice, and histopathologic staining was used to detect cardiac hypertrophy, myocardial fibrosis, and cardiac inflammation. Quantitative real-time polymerase chain reaction was used to detect the expression levels of miR-574-3p and cardiac hypertrophy markers. Western blotting detected the IL-6 (interleukin-6)/JAK/STAT inflammatory signaling pathway. RESULTS: Echocardiography and histochemical staining found that aerobic exercise significantly improved pressure overload-induced myocardial hypertrophy (n=6), myocardial interstitial fibrosis (n=6), and cardiac inflammation (n=6). Quantitative real-time polymerase chain reaction detection showed that aerobic exercise upregulated the expression level of miR-574-3p (n=6). After specific knockdown of miR-574-3p in mouse hearts with adeno-associated virus 9 using cardiac troponin T promoter, we found that the protective effect of exercise training on the heart was significantly reversed. Echocardiography and histopathologic staining showed that inhibiting the expression of miR-574-3p could partially block the effects of aerobic exercise on cardiac function (n=6), cardiomyocyte cross-sectional area (n=6), and myocardial fibrosis (n=6). Western blotting and immunohistochemical staining showed that the inhibitory effects of aerobic exercise on the IL-6/JAK/STAT pathway and cardiac inflammation were partially abolished after miR-574-3p knockdown. Furthermore, we also found that miR-574-3p exerts cardioprotective effects in cardiomyocytes by targeting IL-6 (n=3). CONCLUSIONS: Aerobic exercise protects cardiac hypertrophy and inflammation induced by pressure overload by upregulating miR-574-3p and inhibiting the IL-6/JAK/STAT pathway.

Ga2O3 Bipolar Heterojunction-Based Optoelectronic Synapse Array with Visual Attention.

The human brain efficiently processes only a fraction of visual information, a phenomenon termed attentional control, resulting in energy savings and heightened adaptability. Translating this mechanism into artificial visual neurons holds promise for constructing energy-efficient, bioinspired visual systems. Here, we propose a self-rectifying artificial visual neuron (SEVN) based on a NiO/Ga2O3 bipolar heterojunction with attentional control on patterns with a target color. The device exhibits short-term potentiation (STP) with quantum point contact (QPC) traits at low bias and transitions to long-term potentiation (LTP) at high bias, particularly facilitated by electron capture in deep defects upon ultraviolet (UV) exposure. With the utilization of two wavelengths of light upon the target and interference part of CAPTCHA to simulate top-down attentional control, the recognition accuracy is enhanced from 74 to 84%. These findings have the potential to augment the visual capability of neuromorphic systems with implications for diverse applications, including cybersecurity, healthcare, and machine vision.

Occurrence and partitioning of p-phenylenediamine antioxidants and their quinone derivatives in water and sediment.

p-Phenylenediamine antioxidants (PPDs) and PPDs-derived quinones (PPDQs) may pose a threat to the river ecosystem. However, the knowledge on the occurrence and environmental behaviors of PPDs and PPDQs in the natural river environment remains unknown. In this study, we collected paired water (n = 30) and sediment samples (n = 30) from Jiaojiang River, China and analyzed them for nine PPDs and seven PPDQs. Our results showed that target PPDs and PPDQs are frequently detected in water samples, with the dominance of N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD; mean 12 ng/L, range 4.0-72 ng/L) and 6PPD-derived quinone (6PPDQ; 7.0 ng/L,

Recent progress of Ni-based nanomaterials for the electrocatalytic oxygen evolution reaction at large current density.

The precise design and development of high-performing oxygen evolution reaction (OER) for the production of industrial hydrogen gas through water electrolysis has been a widely studied topic. A profound understanding of the nature of electrocatalytic processes reveals that Ni-based catalysts are highly active toward OER that can stably operate at a high current density for a long period of time. Given the current gap between research and applications in industrial water electrolysis, we have completed a systematic review by constructively discussing the recent progress of Ni-based catalysts for electrocatalytic OER at a large current density, with special focus on the morphology and composition regulation of Ni-based electrocatalysts for achieving extraordinary OER performance. This review will facilitate future research toward rationally designing next-generation OER electrocatalysts that can meet industrial demands, thereby promoting new sustainable solutions for energy shortage and environment issues.

Sphingosylphosphorylcholine alleviates pressure overload-induced myocardial remodeling in mice via inhibiting CaM-JNK/p38 signaling pathway.

Apoptosis plays a critical role in the development of heart failure, and sphingosylphosphorylcholine (SPC) is a bioactive sphingolipid naturally occurring in blood plasma. Some studies have shown that SPC inhibits hypoxia-induced apoptosis in myofibroblasts, the crucial non-muscle cells in the heart. Calmodulin (CaM) is a known SPC receptor. In this study we investigated the role of CaM in cardiomyocyte apoptosis in heart failure and the associated signaling pathways. Pressure overload was induced in mice by trans-aortic constriction (TAC) surgery. TAC mice were administered SPC (10 µM·kg-1·d-1) for 4 weeks post-surgery. We showed that SPC administration significantly improved survival rate and cardiac hypertrophy, and inhibited cardiac fibrosis in TAC mice. In neonatal mouse cardiomyocytes, treatment with SPC (10 µM) significantly inhibited Ang II-induced cardiomyocyte hypertrophy, fibroblast-to-myofibroblast transition and cell apoptosis accompanied by reduced Bax and phosphorylation levels of CaM, JNK and p38, as well as upregulated Bcl-2, a cardiomyocyte-protective protein. Thapsigargin (TG) could enhance CaM functions by increasing Ca2+ levels in cytoplasm. TG (3 µM) annulled the protective effect of SPC against Ang II-induced cardiomyocyte apoptosis. Furthermore, we demonstrated that SPC-mediated inhibition of cardiomyocyte apoptosis involved the regulation of p38 and JNK phosphorylation, which was downstream of CaM. These results offer new evidence for SPC regulation of cardiomyocyte apoptosis, potentially providing a new therapeutic target for cardiac remodeling following stress overload.

Cu2+ -Anchored Carbon Nano-Photocatalysts for Visible Water Splitting to Boost Hydrogen Cuproptosis.

Both hydrogen (H2 ) and copper ions (Cu+ ) can be used as anti-cancer treatments. However, the continuous generation of H2 molecules and Cu+ in specific sites of tumors is challenging. Here we anchored Cu2+ on carbon photocatalyst (Cu@CDCN) to allow the continuous generation of H2 and hydrogen peroxide (H2 O2 ) in tumors using the two-electron process of visible water splitting. The photocatalytic process also generated redox-active Cu-carbon centers. Meanwhile, the Cu2+ residues reacted with H2 O2 (the obstacle to the photocatalytic process) to accelerate the two-electron process of water splitting and cuprous ion (Cu+ ) generation, in which the Cu2+ residue promoted a pro-oxidant effect with glutathione through metal-reducing actions. Both H2 and Cu+ induced mitochondrial dysfunction and intracellular redox homeostasis destruction, which enabled hydrogen therapy and cuproptosis to inhibit cancer cell growth and suppress tumor growth. Our research is the first attempt to integrate hydrogen therapy and cuproptosis using metal-enhanced visible solar water splitting in nanomedicine, which may provide a safe and effective cancer treatment.

Volumes of hippocampal subfields suggest a continuum between schizophrenia, major depressive disorder and bipolar disorder.

Objective: There is considerable debate as to whether the continuum of major psychiatric disorders exists and to what extent the boundaries extend. Converging evidence suggests that alterations in hippocampal volume are a common sign in psychiatric disorders; however, there is still no consensus on the nature and extent of hippocampal atrophy in schizophrenia (SZ), major depressive disorder (MDD) and bipolar disorder (BD). The aim of this study was to verify the continuum of SZ - BD - MDD at the level of hippocampal subfield volume and to compare the volume differences in hippocampal subfields in the continuum. Methods: A total of 412 participants (204 SZ, 98 MDD, and 110 BD) underwent 3 T MRI scans, structured clinical interviews, and clinical scales. We segmented the hippocampal subfields with FreeSurfer 7.1.1 and compared subfields volumes across the three diagnostic groups by controlling for age, gender, education, and intracranial volumes. Results: The results showed a gradual increase in hippocampal subfield volumes from SZ to MDD to BD. Significant volume differences in the total hippocampus and 13 of 26 hippocampal subfields, including CA1, CA3, CA4, GC-ML-DG, molecular layer and the whole hippocampus, bilaterally, and parasubiculum in the right hemisphere, were observed among diagnostic groups. Medication treatment had the most effect on subfields of MDD compared to SZ and BD. Subfield volumes were negatively correlated with illness duration of MDD. Positive correlations were found between subfield volumes and drug dose in SZ and MDD. There was no significant difference in laterality between diagnostic groups. Conclusion: The pattern of hippocampal volume reduction in SZ, MDD and BD suggests that there may be a continuum of the three disorders at the hippocampal level. The hippocampus represents a phenotype that is distinct from traditional diagnostic strategies. Combined with illness duration and drug intervention, it may better reflect shared pathophysiology and mechanisms across psychiatric disorders.

Ca-DEX biomineralization-inducing nuts reverse oxidative stress and bone loss in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a common autoimmune disease, and the inflammatory response during its development can lead to joint cartilage and bone damage up to disability. Dexamethasone (DEX) can effectively alleviate the inflammatory response in RA, but the severe adverse effects that occur after its long-term administration limit its clinical development. Herein, we propose a Ca-DEX biomineralization-inducing nut (CaCO3-DEX) with controlled release properties for mitigating the toxic side effects of DEX in RA treatment, especially the damage to cartilage and bone. CaCO3-DEX releases the drug and Ca2+ preferentially in an inflammatory environment. Both in vitro and in vivo studies demonstrate that CaCO3-DEX significantly reduces the secretion of pro-inflammatory factors and inhibits ROS production in vitro, as well as demonstrates superior pro-biomineralization and osteogenic differentiation potential. In the collagen-induced rheumatoid arthritis model (CIA model), CaCO3-DEX significantly reduces the clinical score of arthritis in mice, and the imaging results show a noticeable relief of edema and bone erosion in CIA model mice treated with CaCO3-DEX, while inflammatory factors at the injury areas are significantly reduced, which provides favorable protection to cartilage and bone.

An avalanche-and-surge robust ultrawide-bandgap heterojunction for power electronics.

Avalanche and surge robustness involve fundamental carrier dynamics under high electric field and current density. They are also prerequisites of any power device to survive common overvoltage and overcurrent stresses in power electronics applications such as electric vehicles, electricity grids, and renewable energy processing. Despite tremendous efforts to develop the next-generation power devices using emerging ultra-wide bandgap semiconductors, the lack of effective bipolar doping has been a daunting obstacle for achieving the necessary robustness in these devices. Here we report avalanche and surge robustness in a heterojunction formed between the ultra-wide bandgap n-type gallium oxide and the wide-bandgap p-type nickel oxide. Under 1500 V reverse bias, impact ionization initiates in gallium oxide, and the staggered band alignment favors efficient hole removal, enabling a high avalanche current over 50 A. Under forward bias, bipolar conductivity modulation enables the junction to survive over 50 A surge current. Moreover, the asymmetric carrier lifetime makes the high-level carrier injection dominant in nickel oxide, enabling a fast reverse recovery within 15 ns. This heterojunction breaks the fundamental trade-off between robustness and switching speed in conventional homojunctions and removes a key hurdle to advance ultra-wide bandgap semiconductor devices for power industrial applications.

Loss of USP22 alleviates cardiac hypertrophy induced by pressure overload through HiF1-α-TAK1 signaling pathway.

Ubiquitin-specific protease 22 (USP22) is a member of the ubiquitin specific protease family (ubiquitin-specific protease, USPs), the largest subfamily of deubiquitinating enzymes, and plays an important role in the treatment of tumors. USP22 is also expressed in the heart. However, the role of USP22 in heart disease remains unclear. In this study, we found that USP22 was elevated in hypertrophic mouse hearts and in angiotensin II (Ang II)-induced cardiomyocytes. The inhibition of USP22 expression with adenovirus significantly rescued hypertrophic phenotype and cardiac dysfunction induced by pressure overloaded. Consistent with in vivo study, silencing by USP22 shRNA expression in vitro had similar results. Molecular analysis revealed that transforming growth factor-ß-activating protein 1 (TAK1)-(JNK1/2)/P38 signaling pathway and HIF-1α was activated in the Ang II-induced hypertrophic cardiomyocytes, whereas HIF-1α expression was decreased after the inhibition of USP22. Inhibition of HIF-1α expression reduces TAK1 expression. Co-immunoprecipitation and ubiquitination studies revealed the regulatory mechanism between USP22 and HIF1α.Under hypertrophic stress conditions, USP22 enhances the stability of HIF-1α through its deubiquitination activity, which further activates the TAK1-(JNK1/2)/P38 signaling pathway to lead to cardiac hypertrophy. Inhibition of HIF-1α expression further potentiates the in vivo pathological effects caused by USP22 deficiency. In summary, this study suggests that USP22, through HIF-1α-TAK1-(JNK1/2)/P38 signaling pathway, may be potential targets for inhibiting pathological cardiac hypertrophy induced by pressure overload.

Comparative Analysis of the Therapeutic Effects of Fresh and Cryopreserved Human Umbilical Cord Derived Mesenchymal Stem Cells in the Treatment of Psoriasis.

Psoriasis, an inflammatory autoimmune skin disease, is characterized by scaly white or erythematous plaques, which severely influence patients' quality of life and social activities. Mesenchymal stem cells derived from the human umbilical cord (UCMSCs) represent a promising therapeutic approach for psoriasis because of its unique superiority in ethical agreeableness, abundant source, high proliferation capacity, and immunosuppression. Although cryopreservation provided multiple benefits to the cell therapy, it also greatly compromised clinical benefits of MSCs due to impaired cell functions. The current study aims to evaluate the therapeutic efficacy of cryopreserved UCMSCs in a mouse model of psoriasis as well as in patients with psoriasis. Our results showed that cryopreserved and fresh UCMSCs have comparable effects on the suppression of psoriasis-like symptoms such as thickening, erythema, and scaling, and serum IL-17 A secretion in mice model of psoriasis. Moreover, psoriatic patients injected with cryopreserved UCMSCs had a significant improvement in the Psoriasis Area and Severity Index (PASI), Physician Global Assessment (PGA), and Patient Global Assessments (PtGAs) scores compared to baseline values. Mechanically, cryopreserved UCMSCs markedly inhibit the proliferation of PHA-activated PBMCs, type 1 T helper (Th1) and type 17 T helper (Th17) cell differentiation and secretion of inflammatory cytokines including IFN-γ, TNF-a and IL-17 A in PBMCs stimulated by anti-CD3/CD28 beads. Taken together, these data indicated that cryopreserved UCMSCs exhibited great beneficial effect on psoriasis. Thus, cryopreserved UCMSCs can be systemically administered as ''off-the-shelf'' cell product for psoriasis therapy. Trial Registration ChiCTR1800019509. Registered on November 15, 2018-Retrospectively registered, http://www.chictr.org.cn/ .

Do inconsistent mental models impact performance? Moderating effects of managerial interpretation and practice sets.

Deviant cognition, referring to team members' different understanding of goals or rules, results in inconsistent mental models among the team. Although previous studies have examined the negative effects of inconsistent mental models on deviant behavior and performance in the workplace, they have failed to consider their positive effects and moderating mechanisms, thus limiting our understanding of how to manage inconsistent mental models and deviant cognition. To address this research gap, this study builds on the interpretation and information processing theory, which regards mental models as the result of information processing, especially involving interactions where interpretation of the information is required. The study initially recruited 174 team managers as participants to identify instances of managerial interpretation. The team managers' interpretation modes were then categorized into four types (absorb, shift, limit, and explore), and a questionnaire was developed to measure them. The moderating effects of the modes on execution and innovation performance were also examined. Matched data were then collected from interviews with 104 team managers and 312 of their team members. The regression results showed that absorb, shift, and limit interpretation modes, as well as the practice sets involving managers and members, attenuated the negative relationship between inconsistent mental models and execution performance. The explore interpretation mode and the practice sets enhanced the positive relationship between inconsistent mental models and team innovation. The findings of this study help to understand the cognitive level of deviance in teams and the moderating effects of managerial interpretation on the relationship between deviant cognition, or inconsistent mental models, and performance, suggesting the need to study and utilize the positive roles of inconsistent mental models or deviance through managerial interpretation. The results also call for firms to train managers' interpretation skills and design close working links with team members.