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Thermal/environmental barrier coatings (T/EBCs) are used to protect hot-section superalloys and/or ceramic matrix composite components from hot corrosion and oxidation; however, the majority of T/EBCs exhibit extremely high thermal and ionic conductivities. Here, we obtain a novel rare-earth tantalate with excellent oxygen and thermal insulation via a high-entropy strategy. The high-entropy component (8RE1/8)TaO4 (RE = rare earth), which is designed by large size disorder and mass disorder, has been reassembled into a stabilized monoclinic structure. (8RE1/8)TaO4 had 30.0%–31.1% and 59.2%–67.5% lower intrinsic thermal conductivity than single-RE RETaO4 and 8(Y2O3–ZrO2) 8YSZ at 1200 °C, respectively, and exhibited lower intrinsic thermal conductivity across the entire temperature range of 100–1200 °C. This is the result of strong scattering by the phonon–phonon, grain boundary, domain boundary, dislocation, and vacancy defects. The ionic conductivity of (8RE1/8)TaO4 is 3712–29,667 times lower than that of 8YSZ at 900 °C, benefiting from the strong Ta–O bonding strength, low concentration of mobile oxygen vacancies and severe lattice distortions that impede carrier transport. Moreover, (8RE1/8)TaO4 had superior high-temperature stability and excellent mechanical properties. Analysis of above results demonstrates that (8RE1/8)TaO4 is a promising candidate for T/EBCs.

Abstract Background The use of mesenchymal stem cells (MSCs) is recognized as a promising strategy for the treatment of androgenetic alopecia (AGA). However, the underlying mechanism remains to be explored. Here, we evaluated the therapeutic effects and potential mechanisms of the use of human umbilical cord mesenchymal stem cells (hUCMSCs) in dihydrotestosterone (DHT)-induced AGA models in vivo and in vitro. Methods Intradermal transplantation of hUCMSCs was performed in AGA model mice and therapeutic effects were evaluated using histological and immunofluorescence staining. Transwell assays were used for co-culture of hUCMSCs and dermal papilla cells (DPCs), and communication was assessed using RT-qPCR, immunofluorescence, and apoptosis analysis. Interactions between DPCs and hair follicle stem cells (HFSCs) were investigated using RT-qPCR, EdU assays, and cell cycle analysis. Results Treatment of AGA mice with hUCMSCs promoted hair growth, HFs density, skin thickness, and anagen phase activation, while inhibiting DPCs apoptosis, and promoting HFSCs proliferation. In vitro, hUCMSCs activated Wnt/β-catenin signaling in DPCs via Wntless (Wls), while stimulating growth factor secretion and HFSCs proliferation. Blocking β-catenin degradation with MSAB increased DPCs apoptosis, reduced growth factor secretion, and retarded HFSCs proliferation. Conclusion hUCMSCs promoted hair regeneration in AGA model mice. This was found to be dependent on reducing DPCs apoptosis, thereby relieving the inhibitory effects of DPCs on the growth of HFSCs. The activation of the Wnt/β-catenin signaling pathway was shown to play a crucial role in the promotion of hair growth by hUCMSCs in AGA mice.

Background: This study aimed to construct and internally validate a probability of the return of spontaneous circulation (ROSC) rate nomogram in a Chinese population of patients with cardiac arrest (CA). Methods: Patients with CA receiving standard cardiopulmonary resuscitation (CPR) were studied retrospectively. The minor absolute shrinkage and selection operator (LASSO) regression analysis and multivariable logistic regression evaluated various demographic and clinicopathological characteristics. A predictive nomogram was constructed and evaluated for accuracy and reliability using C-index, the area under the receiver operating characteristic curve (AUC), calibration plot, and decision curve analysis (DCA). Results: A cohort of 508 patients who had experienced CA and received standard CPR was randomly divided into training (70 %, n = 356) and validation groups (30 %, n = 152) for the study. LASSO regression analysis and multivariable logistic regression revealed that thirteen variables, such as age, CPR start time, Electric defibrillation, Epinephrine, Sodium bicarbonate (NaHCO3), CPR Compression duration, The postoperative prothrombin (PT) time, Lactate (Lac), Cardiac troponin (cTn), Potassium (K+), D-dimer, Hypertension (HBP), and Diabetes mellitus (DM), were found to be independent predictors of the ROSC rate of CPR. The nomogram model showed exceptional discrimination, with a C-index of 0.933 (95 % confidence interval: 0.882–0.984). Even in the internal validation, a remarkable C-index value of 0.926 (95 % confidence interval: 0.875–0.977) was still obtained. The accuracy and reliability of the model were also verified by the AUC of 0.923 in the training group and 0.926 in the validation group. The calibration curve showed the model agreed with the actual results. DCA suggested that the predictive nomogram had clinical utility. Conclusions: A predictive nomogram model was successfully established and proved to identify the influencing factors of the ROSC rate in patients with CA. During cardiopulmonary resuscitation, adjusting the emergency treatment based on the influence factors on ROSC rate is suggested to improve the treatment rate of patients with CA.

In hyperspectral image (HSI) classification, combining the strengths of convolutional neural networks (CNNs) and Transformers can significantly enhance classification performance and model robustness. However, neural networks that combine CNNs and Transformers face classification accuracy and generalization limitations when dealing with imbalanced class samples, particularly in few-shot training scenarios. To solve the above problems, we propose a multi-scale spatial perception attention network (Ms-SPA) for few-shot HSI classification in this article. This method is based on an encoder-decoder fully convolutional network (FCN) architecture, where the encoder combines a convolutional neural network (CNN) with a Transformer module to extract local and global spatial-spectral joint features simultaneously. In the encoder, the spatial contraction perception Transformer (SCPFormer) is first proposed to improve the model’s capacity for perceiving global-local joint features. Next, the multi-scale spatial attention (MSSA) module is proposed to capture spatial information at different convolution kernel scales and cascade them to form a more comprehensive representation structure. In the decoder, adaptive residual aggregation (ARA) is proposed to embed high-level semantic information into low-level features using a residual structure, thereby enhancing the perception of contextual information. A weighted CL-MixedLoss function (CL-MixedLoss) is proposed to solve the problem of imbalanced heterogeneous pixels in HSIs. Experimental results on three renowned HSI datasets indicate that our model achieves optimal classification performance, exceeding 95%, even when trained with a limited number of class samples.

Abstract The expression levels and prognostic role of AP3M2 in colorectal adenocarcinoma (CRAC) have yet to be fully unveiled. Our study comprehensively investigated the clinical significance of AP3M2 in colorectal cancer through an extensive bioinformatics data mining process (TCGA, GEO, GEPIA, Timer, Ualcan, ROCPLOT, and David), followed by experimental validation. We found AP3M2 is a cancer gene, which can be used to distinguish between colorectal cancer and colorectal adenomas, liver metastasis, lung metastasis, colorectal polyp. Higher AP3M2 expression levels were associated with longer overall survival in colon adenocarcinoma. AP3M2 might be the primary biomarker for oxaliplatin in colon cancer and an acquired resistance biomarker for oxaliplatin and 5-fu. AP3M2 was positively associated with CD274, CTLA4. AP3M2 might be associated with T-cell, NF-kappaB transcription factor activity, and response to hypoxia. AP3M2 could predict chemotherapy effectiveness and prognosis for colon cancer patients. AP3M2 might inhibit tumor growth via influencing tumor-infiltrating immune cells in the context of Tumor microenvironment. AP3M2 plays as an oncogene in CRAC and is suggested as a new potential biotarget for therapy.

Purposes To address the imbalance between supply and demand in traditional single platform task assignment, Cross Online Matching (COM) has emerged as a novel solution that allows multiple similar platforms to establish cooperative relationships and send uncompleted tasks to other platforms, increasing the probability of task acceptance. However, current COM solutions only consider single-round matching processes, making it difficult to find optimal decision results in multi-platform competition. To settle these limitations, the Multi-Round Cross Online Matching problem (MRCOM) is studied and Greedy-based Multi-Round Cross Online Matching (G-MRCOM) and Game-Theoretic Multi-Round Cross Online Matching (GT-MRCOM) algorithms are proposed. Methods G-MRCOM improves task completion efficiency by forwarding and matching tasks in multiple rounds, with platforms greedily selecting high-reward tasks to accomplish. GT-MRCOM, on the other hand, establishes incentive mechanisms among algorithms cooperating platforms, calculates task assignment strategies that satisfy Nash Equilibrium, and enables the platform to find better strategies in competition, thereby enhancing overall performance. Findings Experimental results demonstrate that the proposed algorithms can increase the total revenue of platforms, showcasing the effectiveness and efficiency of this study.

Thermal barrier coating (TBC) materials can improve energy conversion efficiency and reduce fossil fuel use. Herein, novel rare earth tantalates RETaO4, as promising candidates for TBCs, were reassembled into multi-component solid solutions with a monoclinic structure to further depress thermal conductivity via an entropy strategy. The formation mechanisms of oxygen vacancy defects, dislocations, and ferroelastic domains associated with the thermal conductivity are demonstrated by aberration-corrected scanning transmission electron microscopy. Compared to single-RE RETaO4 and 8YSZ, the intrinsic thermal conductivity of (5RE1/5)TaO4 was decreased by 35%–47% and 57%–69% at 1200 ℃, respectively, which is likely attributed to multi-scale phonon scattering from Umklapp phonon–phonon, point defects, domain structures, and dislocations. r¯RE3+/rTa5+ and low-temperature thermal conductivity are negatively correlated, as are the ratio of elastic modulus to thermal conductivity (E/κ) and high-temperature thermal conductivity. Meanwhile, the high defects’ concentration and lattice distortion in high-entropy ceramics enhance the scattering of transverse-wave phonons and reduce the transverse-wave sound velocity, leading to a decrease in the thermal conductivity and Young’s modulus. In addition, 5HEC-1 has ultra-low thermal conductivity, moderate thermal expansion coefficients, and high hardness among three five-component high-entropy samples. Thus, 5HEC-1 with superior thermal barrier and mechanical properties can be used as promising thermal insulating materials.

ABSTRACTMosquito-borne viruses cause various infectious diseases in humans and animals. Tibet orbivirus (TIBOV), a newly identified arbovirus, efficiently replicates in different types of vertebrate and mosquito cells, with its neutralizing antibodies detected in cattle and goats. However, despite being isolated from Culicoides midges, Anopheles, and Culex mosquitoes, there has been a notable absence of systematic studies on its vector competence. Thus, in this study, Aedes aegypti and Culex pipiens pallens were reared in the laboratory to measure vector susceptibility through blood-feeding infection. Furthermore, RNA sequencing was used to examine the overall alterations in the Ae. aegypti transcriptome following TIBOV infection. The results revealed that Ae. aegypti exhibited a high susceptibility to TIBOV compared to Cx. p. pallens. Effective replication of the virus in Ae. aegypti midguts occurred when the blood-feeding titer of TIBOV exceeded 105 plaque-forming units mL−1. Nevertheless, only a few TIBOV RNA-positive samples were detected in the saliva of Ae. aegypti and Cx. p. pallens, suggesting that these mosquito species may not be the primary vectors for TIBOV. Moreover, at 2 dpi of TIBOV, numerous antimicrobial peptides downstream of the Toll and Imd signaling pathways were significantly downregulated in Ae. aegypti, indicating that TIBOV suppressed mosquitos’ defense to survive in the vector at an early stage. Subsequently, the stress-activated protein kinase JNK, a crucial component of the MAPK signaling pathway, exhibited significant upregulation. Certain genes were also enriched in the MAPK signaling pathway in TIBOV-infected Ae. aegypti at 7 dpi.IMPORTANCETibet orbivirus (TIBOV) is an understudied arbovirus of the genus Orbivirus. Our study is the first-ever attempt to assess the vector susceptibility of this virus in two important mosquito vectors, Aedes aegypti and Culex pipiens pallens. Additionally, we present transcriptome data detailing the interaction between TIBOV and the immune system of Ae. aegypti, which expands the knowledge about orbivirus infection and its interaction with mosquitoes.

Abstract The damage variation of a masonry structure during shield tunneling has been investigated. Furthermore, the damage degree of the masonry building has been investigated by combining the field measurement, finite element method results, and theoretical method. The results show that compared with the theoretical calculation method LSTM, the method provide by this paper can give the detail damage location of the masonry structure caused by shield construction. Due to the existence of door and window openings, the result of JMM is larger than LSTM result, the differences can be modified by concept of “characteristic tensile strain”. The wall of the masonry building encounter the shield face first suffers more damage than the later ones. At the beginning of tunnlling, the damage were generated from a small area at the bottom for wall 1, but a larger area at the top of the building for wall 2. The damage area increase more at the top of the building as tunneling advanced, but the maximum damage occurred at the bottom of the building.

Abstract Incoherent interfaces with large mismatches usually exhibit very weak interfacial interactions so that they rarely generate intriguing interfacial properties. Here we demonstrate unexpected strong interfacial interactions at the incoherent AlN/Al2O3 (0001) interface with a large mismatch by combining transmission electron microscopy, first-principles calculations, and cathodoluminescence spectroscopy. It is revealed that strong interfacial interactions have significantly tailored the interfacial atomic structure and electronic properties. Misfit dislocation networks and stacking faults are formed at this interface, which is rarely observed at other incoherent interfaces. The band gap of the interface reduces significantly to ~ 3.9 eV due to the competition between the elongated Al-N and Al-O bonds across the interface. Thus this incoherent interface can generate a very strong interfacial ultraviolet light emission. Our findings suggest that incoherent interfaces can exhibit strong interfacial interactions and unique interfacial properties, thereby opening an avenue for the development of related heterojunction materials and devices.

Indoor dust contaminated with liquid crystal monomers (LCMs) released from various commercial liquid crystal display (LCD) screens may pose environmental health risks to humans. This study aimed to investigate the occurrence of 64 LCMs in ventilation and air conditioning filters (VACF) dust, characterize their composition profiles, potential sources, and associations with indoor characteristics, and assess their in vitro toxicity using the human lung bronchial epithelial cells (BEAS-2B). A total of 31 LCMs with concentrations (ΣLCMs) ranging from 43.7 ng/g to 448 ng/g were detected in the collected VACF dust. Additional analysis revealed the potential interactions between indoor environmental conditions and human exposure risks associated with the detected LCMs in VACF dust. The service area and working time of the ventilation and air conditioning system, and the number of indoor LCD screens were positively correlated with the fluorinated ΣLCMs in VACF dust (r = 0.355 ∼ 0.511, p 0.05), suggesting different environmental behavior and fates of fluorinated and non-fluorinated LCMs in the indoor environment. Four main indoor sources of LCMs (i.e., computer (37.1%), television (28.3%), Brand A smartphone (21.2%) and Brand S smartphone (13.4%)) were identified by positive matrix factorization-multiple linear regression (PMF-MLR). Exposure to 14 relatively frequently detected LCMs, individually and in the mixture, induced significant oxidative stress in BEAS-2B cells. Among them, non-fluorinated LCMs, specifically 3cH2B and MeP3bcH, caused dominant decreased cell viability. This study provides new insights into the indoor LCMs pollution and the associated potential health risks due to the daily use of electronic devices.

Abstract Renal fibrosis is a common characteristic of various chronic kidney diseases (CKDs) driving the loss of renal function. During this pathological process, persistent injury to renal tubular epithelial cells and activation of fibroblasts chiefly determine the extent of renal fibrosis. In this study, the role of tumor protein 53 regulating kinase (TP53RK) in the pathogenesis of renal fibrosis and its underlying mechanisms is investigated. TP53RK is upregulated in fibrotic human and animal kidneys with a positive correlation to kidney dysfunction and fibrotic markers. Interestingly, specific deletion of TP53RK either in renal tubule or in fibroblasts in mice can mitigate renal fibrosis in CKD models. Mechanistic investigations reveal that TP53RK phosphorylates baculoviral IAP repeat containing 5 (Birc5) and facilitates its nuclear translocation; enhanced Birc5 displays a profibrotic effect possibly via activating PI3K/Akt and MAPK pathways. Moreover, pharmacologically inhibiting TP53RK and Birc5 using fusidic acid (an FDA‐approved antibiotic) and YM‐155(currently in clinical phase 2 trials) respectively both ameliorate kidney fibrosis. These findings demonstrate that activated TP53RK/Birc5 signaling in renal tubular cells and fibroblasts alters cellular phenotypes and drives CKD progression. A genetic or pharmacological blockade of this axis serves as a potential strategy for treating CKDs.

Wound age estimation is a crucial and challenging problem in forensic pathology. Although mRNA is the most commonly used indicator for wound age estimation, screening criteria are lacking. In the present study, the feasibility of screening criteria using mRNA to determine injury time based on the adenylate-uridylate-rich element (ARE) structure and gene ontology (GO) categories were evaluated. A total of 78 Sprague-Dawley male rats were contused and sampled at 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48 h after inflicting injury. The candidate mRNAs were classified based on with or without ARE structure and GO category function. The mRNA expression levels were detected using qRT-PCR. In addition, the standard deviation (STD), mean deviation (MD), relative average deviation (d%), and coefficient of variation (CV) were calculated based on mRNA expression levels. The CV score (CVs) and the CV of CV (CV’CV) were calculated to measure heterogeneity. Finally, based on classic principles, the accuracy of combination of candidate mRNAs was assessed using discriminant analysis to construct a multivariate model for inferring wound age. The results of homogeneity evaluation of each group based on CVs were consistent with the MD, STD, d%, and CV results, indicating the credibility of the evaluation results based on CVs. The candidate mRNAs without ARE structure and classified as cellular component (CC) GO category (ARE–CC) had the highest CVs, showing the mRNAs with these characteristics are the most homogenous mRNAs and best suited for wound age estimation. The highest accuracy was 91.0% when the mRNAs without ARE structure were used to infer the wound age based on the discrimination model. The accuracy of mRNAs classified into CC or multiple function (MF) GO category was higher than mRNAs in the biological process (BP) category. In all subgroups, the accuracy of the composite identification model of mRNA composition without ARE structure and classified as CC was higher than other subgroups. The mRNAs without ARE structure and belonging to the CC GO category were more homogenous, showed higher accuracy for estimating wound age, and were appropriate for rat skeletal muscle wound age estimation.

BackgroundWorldwide, mental well-being is a critical issue for public health, especially among medical staff; it affects professionalism, efficiency, quality of care delivery, and overall quality of life. Nevertheless, assessing mental well-being is a complex problem. ObjectiveThis study aimed to evaluate the psychometric properties of the Chinese-language version of the 14-item Warwick-Edinburgh Mental Well-being Scale (WEMWBS) in medical staff recruited mainly from 6 hospitals in China and provide a reliable measurement of positive mental well-being. MethodsA cross-sectional online survey was conducted of medical staff from 15 provinces in China from May 15 to July 15, 2020. Confirmatory factor analysis (CFA) was conducted to test the structure of the Chinese WEMWBS. The Spearman correlations of the Chinese WEMWBS with the 5-item World Health Organization Well-Being Index (WHO-5) were used to evaluate convergent validity. The Cronbach α and split-half reliability (λ) represented internal consistency. A graded response model was adopted for an item response theory (IRT) analysis. We report discrimination, difficulty, item characteristic curves (ICCs), and item information curves (IICs). ICCs and IICs were used to estimate reliability and validity based on the IRT analysis. ResultsA total of 572 participants from 15 provinces in China finished the Chinese WEMWBS. The CFA showed that the 1D model was satisfactory and internal consistency reliability was excellent, with α=.965 and λ=0.947, while the item-scale correlation coefficients ranged from r=0.727 to r=0.900. The correlation coefficient between the Chinese WEMWBS and the WHO-5 was significant, at r=0.746. The average variance extraction value was 0.656, and the composite reliability value was 0.964, with good aggregation validity. The discrimination of the Chinese WEMWBS items ranged from 2.026 to 5.098. The ICCs illustrated that the orders of the category thresholds for the 14 items were satisfactory. ConclusionsThe Chinese WEMWBS showed good psychometric properties and can measure well-being in medical staff.

Background: Chromosome 5 open reading frame 46 (C5ORF46), also known as antimicrobial peptide with 64 amino acid residues (AP-64) and skin and saliva-secreted protein 1 (SSSP1), belongs to the family of open reading frame genes and encodes a small exosomal protein. C5ORF46 has been implicated in antibacterial activity and associated with patient prognosis in pancreatic cancer, colorectal cancer, and stomach cancer. These findings highlight the importance of C5ORF46 in gastrointestinal (GI) tumor inception and development. However, the prognostic and immunological value of C5ORF46 in human GI tumors remains largely unknown. In this study, we sought to explore the potential value of C5ORF46 in GI tumor prognosis and immunology.Method: RNA sequencing (RNA-seq) was performed on the tumor and tumor-adjacent normal samples we collected to identify potential target genes for GI tumors. Apart from our RNA-seq data, all original data were downloaded from The Cancer Genome Atlas (TCGA) database and integrated via Strawberry Perl (v 5.32.0) and R (v 4.1.1). The differential expression of C5ORF46 was examined with Oncomine, Tumor Immune Estimation Resource (TIMER), Gene Expression Profiling Interactive Analysis (GEPIA), Cancer Cell Line Encyclopedia (CCLE), the Human Protein Atlas (HPA) and TCGA databases. The c-BioPortal database was used to investigate the genomic alterations of C5ORF46. The effect of C5ORF46 on prognosis and clinical phenotypes was explored via bioinformatics analyses on the TCGA and GEPIA databases. We used the bioinformatics analyses based on the TCGA database to analyze tumor mutational burden (TMB), microsatellite instability (MSI), tumor immune cell infiltration, and the correlations between C5ORF46 expression and several immune-related genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was carried out via the DAVID website and presented as bubble charts using ShengXinRen online tools. Gene set enrichment analysis (GSEA) was performed using R scripts based on data downloaded from the GSEA website. Immunohistochemistry (IHC) was used to validate the expression of C5ORF46 in GI tumors.Results: The results of our RNA-seq data indicated a critical role for C5ORF46 in colon carcinogenesis. Consistently, we demonstrated that C5ORF46 was highly expressed in tumor tissues compared to normal tissues in human GI tumors. Moreover, a strong correlation was observed between C5ORF46 expression levels and patient prognosis, staging, TMB, MSI, and immune cell infiltration. Further, C5ORF46 presented as an important regulator in the tumor microenvironment (TME) and was active in the regulation of cancer immune functions. C5ORF46 is significantly correlated with genes regulating inflammation and immune responses.Conclusion:C5ORF46 may serve as a biomarker for GI tumor prognosis and immunology. C5ORF46 could be a novel target for GI tumor immunotherapy.

Abstract Pyroptosis, one kind of inflammatory regulated cell death, is involved in various inflammatory diseases, including acute kidney injury (AKI). Besides Gasdermin D (GSDMD), GSDME is a newly identified mediator of pyroptosis via the cleavage of caspase-3 generating pyroptotic GSDME-N. Here, we investigated the role of GSDME in renal cellular pyroptosis and AKI pathogenesis employing GSDME-deficient mice and human tubular epithelial cells (TECs) with the interventions of pharmacological and genetic approaches. After cisplatin treatment, GSDME-mediated pyroptosis was induced as shown by the characteristic pyroptotic morphology in TECs, upregulated GSDME-N expression and enhanced release of IL-1β and LDH, and decreased cell viability. Strikingly, silencing GSDME in mice attenuated acute kidney injury and inflammation. The pyroptotic role of GSDME was also verified in human TECs in vitro. Further investigation showed that inhibition of caspase-3 blocked GSDME-N cleavage and attenuated cisplatin-induced pyroptosis and kidney dysfunction. Moreover, deletion of GSDME also protected against kidney injury induced by ischemia-reperfusion. Taken together, the findings from current study demonstrated that caspase-3/GSDME-triggered pyroptosis and inflammation contributes to AKI, providing new insights into the understanding and treatment of this disease.

Hypoxia inducible factors (HIFs) and their regulatory hydroxylases the prolyl hydroxylase domain enzymes (PHDs) are the key mediators of the cellular response to hypoxia. HIFs are normally hydroxylated by PHDs and degraded, while under hypoxia, PHDs are suppressed, allowing HIF-α to accumulate and transactivate multiple target genes, including erythropoiesis, and genes participate in angiogenesis, iron metabolism, glycolysis, glucose transport, cell proliferation, survival, and so on. Aiming at stimulating HIFs, a group of small molecules antagonizing HIF-PHDs have been developed. Of these HIF-PHDs inhibitors (HIF-PHIs), roxadustat (FG-4592), daprodustat (GSK-1278863), vadadustat (AKB-6548), molidustat (BAY 85-3934) and enarodustat (JTZ-951) are approved for clinical usage or have progressed into clinical trials for chronic kidney disease (CKD) anemia treatment, based on their activation effect on erythropoiesis and iron metabolism. Since HIFs are involved in many physiological and pathological conditions, efforts have been made to extend the potential usage of HIF-PHIs beyond anemia. This paper reviewed the progress of preclinical and clinical research on clinically available HIF-PHIs in pathological conditions other than CKD anemia.

Renal fibrosis contributes to kidney dysfunction in various chronic kidney diseases (CKDs). Renal fibrosis can be driven by renal tubular cell death and inflammation. Deletion of gasdermin E (GSDME), an executor of pyroptosis, has been reported to suppress renal tubular cell pyroptosis in several models of kidney injury. However, additional evidence confirming the role of GSDME in regulating renal fibrosis and kidney function in different CKDs is required. In our study, N-GSDME expression was significantly elevated in CKD models in vivo and in vitro. GSDME deletion alleviated renal fibrosis and inflammation in both unilateral ureteral ligation (UUO) and 5/6 nephrectomy (5/6Nx) models along with the attenuation of renal dysfunction. N-GSDME overexpression had a detrimental effect on fibrotic responses in UUO kidneys and TGF-β1-treated renal tubular epithelial cells. In addition, administration of caspase-3 inhibitor Z-DEVD-FMK, which inhibits caspase-3-mediated GSDME cleavage, protected against renal fibrosis both in vivo and in vitro. Collectively, these results provide evidence that the activation of GSDME is critical in regulating both renal fibrosis and kidney dysfunction possibly via promoting inflammatory responses in CKD. These findings may offer new insights into the identification of new therapeutic targets for protecting against CKDs.

The Fujian oyster (Crassostrea angulate) is an important marine bivalve mollusk with high economic value. Gene function research and gene editing techniques have broad application prospects in oyster. The clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) system has been widely used for genome engineering in many species. CRISPR-mediated gene editing has also been used successfully in the Pacific oyster through direct delivery of the CRISPR/Cas9 components into oyster embryos by microinjection. However, the low throughput and operational difficulties associated with microinjection is one of the factors limiting the widespread application of CRISPR/Cas9 in oysters. In this study, we attempted to deliver the CRISPR/Cas9-system into the embryos of C. angulate by electroporation. An all-in-one CRISPR/Cas9 vector plasmid was used as CRISPR/Cas9 system in this study. Electroporation was carried out using both eggs and blastula larvae. A large number of larvae became malformed or die after electroporation. A single base substitution mutation was detected in the D-larvae developed from electroporated eggs. Our results demonstrate that the CRISPR/Cas9 system can be delivered into embryos of C. angulate for gene editing by electroporation, which provides a reference and will further contribute to the future application of electroporation in mollusks.

Photodynamic therapy (PDT) is considered a potential treatment regimen for colorectal cancer cases (CRC). p53 signaling and the miR-124/iASPP axis play an essential role in the PDT resistance of CRC cells. PDT treatment downregulated NEAT1 expression in p53wt HCT116 and RKO cells. In these two cell lines, NEAT1 silencing enhanced the suppressive effects of PDT on cell viability and apoptosis. Within the subcutaneously implanted tumor model, NEAT1 silencing enhanced PDT-induced suppression on tumor growth. Regarding p53-deleted HCT116 cells, PDT only moderately affected cell proliferation but induced downregulation of NEAT1. NEAT1 directly targeted miR-124, acting as a ceRNA, competing with iASPP for miR-124 binding, and counteracting miR-124–mediated repression on iASPP under PDT treatment. NEAT1 silencing was enhanced, whereas miR-124 inhibition attenuated PDT effects on CRC cells; miR-124 inhibition significantly reversed the roles of NEAT1 silencing in PDT-treated CRC cells. miR-124 negatively correlated with NEAT1 and iASPP, respectively, whereas NEAT1 and iASPP positively correlated with each other. PDT downregulated c-Myc in CRC cells, and c-Myc activated the transcription of NEAT1 through the targeting of its promoter region. Within p53mut SW480 cells, PDT failed to alter cell viability and apoptosis but still downregulated c-Myc, NEAT1, and iASPP and upregulated miR-124. In p53 mutant high-abundant CRC tissues, c-Myc and NEAT1 were up-regulated, and miR-124 was downregulated. In c-Myc high-abundant CRC tissues, NEAT1 and iASPP were up-regulated, and miR-124 was downregulated. The critical role of the c-Myc/NEAT1 axis in mediating CRC response to PDT treatment via the miR-124/iASPP/p53 feedback loop was conclusively demonstrated.

Following skeletal muscle injury (SMI), from post-injury reaction to repair consists of a complex series of dynamic changes. However, there is a paucity of research on detailed transcriptional dynamics and time-dependent marker gene expression in the early stages after SMI. In this study, skeletal muscle tissue in rats was taken at 4 to 48 h after injury for next-generation sequencing. We examined the transcriptional kinetics characteristics during above time periods after injury. STEM and maSigPro were used to screen time-correlated genes. Integrating 188 time-correlated genes with 161 genes in each time-related gene module by WGCNA, we finally identified 18 network-node regulatory genes after SMI. Histological staining analyses confirmed the mechanisms underlying changes in the tissue damage to repair process. Our research linked a variety of dynamic biological processes with specific time periods and provided insight into the characteristics of transcriptional dynamics, as well as screened time-related biological indicators with biological significance in the early stages after SMI.

Retinoic acid (RA) signaling pathways mediated by RA receptors (RARs) are essential for many physiological processes such as organ development, regeneration, and differentiation in animals. Recent studies reveal that RARs identified in several mollusks, including Pacific oyster Crassostrea gigas, have a different function mechanism compared with that in chordates. In this report, we identified the molecular characteristics of CgRAR to further explore the mechanism of RAR in mollusks. RT-qPCR analysis shows that CgRAR has a higher expression level in the hemocytes and gonads, indicating that CgRAR may play roles in the processes of development and metabolism. The mRNA expression level of both CgRAR and CgRXR was analyzed by RT-qPCR after injection with RA. The elevated expression of CgRAR and CgRXR was detected upon all-trans-RA (ATRA) exposure. Finally, according to the results of Yeast Two-Hybrid assay and co-immunoprecipitation analysis, CgRAR and CgRXR can interact with each other through the C-terminal region. Taken together, our results suggest that CgRAR shows a higher expression level in gonads and hemocytes. ATRA exposure up-regulates the expression of CgRAR and CgRXR. Besides, CgRAR can interact with CgRXR to form a heterodimer complex.