Metastasis serves as an indicator of malignancy and is a biological characteristic of carcinomas. Epithelial-mesenchymal transition (EMT) plays a key role in the promotion of tumor invasion and metastasis and in the enhancement of tumor cell aggressiveness. Prostaglandin E synthase 3 (p23) is a cochaperone for heat shock protein 90 (HSP90). Our previous study showed that p23 is an HSP90-independent transcription factor in cancer-associated inflammation. The effect and mechanism of action of p23 on lung cancer metastasis are tested in this study. By utilizing cell models in vitro and mouse tail vein metastasis models in vivo, the results provide solid evidence that p23 is critical for promoting lung cancer metastases by regulating downstream CXCL1 expression. Rather than acting independently, p23 forms a complex with RNA-binding motif protein 14 (RBM14) to facilitate EMT progression in lung cancer. Therefore, our study provides evidence for the potential role of the RBM14-p23-CXCL1-EMT axis in the metastasis of lung cancer.

Elemene is widely recognized as an effective anti-cancer compound and is routinely administered in Chinese clinical settings for the management of several solid tumors, including non-small cell lung cancer (NSCLC). However, its detailed molecular mechanism has not been adequately demonstrated. In this research, it was demonstrated that elemene effectively curtailed NSCLC growth in the patient-derived xenograft (PDX) model. Mechanistically, employing high-throughput screening techniques and subsequent biochemical validations such as microscale thermophoresis (MST), microRNA-145-5p (miR-145-5p) was pinpointed as a critical target through which elemene exerts its anti-tumor effects. Interestingly, elemene serves as a binding stabilizer for miR-145-5p, demonstrating a strong binding affinity (dissociation constant (K _D) = 0.39 ± 0.17 μg/mL) and preventing its degradation both in vitro and in vivo, while not interfering with the synthesis of the primary microRNA transcripts (pri-miRNAs) and precursor miRNAs (pre-miRNAs). The stabilization of miR-145-5p by elemene resulted in an increased level of this miRNA, subsequently suppressing NSCLC progression through the miR-145-5p/mitogen-activated protein kinase kinase kinase 3 (MAP3K3)/nuclear factor kappaB (NF-κB) pathway. Our findings provide a new perspective on revealing the interaction patterns between clinical anti-tumor drugs and miRNAs.

OBJECTIVE: To explore the risk factors of acute respiratory distress syndrome (ARDS) in patients with sepsis and to construct a risk nomogram model. METHODS: The clinical data of 234 sepsis patients admitted to the intensive care unit (ICU) of Tianjin Hospital from January 2019 to May 2022 were retrospectively analyzed. The patients were divided into non-ARDS group (156 cases) and ARDS group (78 cases) according to the presence or absence of ARDS. The gender, age, hypertension, diabetes, coronary heart disease, smoking history, history of alcoholism, temperature, respiratory rate (RR), mean arterial pressure (MAP), pulmonary infection, white blood cell count (WBC), hemoglobin (Hb), platelet count (PLT), prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), D-dimer, oxygenation index (PaO₂/FiO₂), lactic acid (Lac), procalcitonin (PCT), brain natriuretic peptide (BNP), albumin (ALB), blood urea nitrogen (BUN), serum creatinine (SCr), acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA) were compared between the two groups. Univariate and multivariate Logistic regression were used to analyze the risk factors of sepsis related ARDS. Based on the screened independent risk factors, a nomogram prediction model was constructed, and Bootstrap method was used for internal verification. The receiver operator characteristic curve (ROC curve) was drawn, and the area under the ROC curve (AUC) was calculated to verify the prediction and accuracy of the model. RESULTS: There were no significant differences in gender, age, hypertension, diabetes, coronary heart disease, smoking history, alcoholism history, temperature, WBC, Hb, PLT, PT, APTT, FIB, PCT, BNP and SCr between the two groups. There were significant differences in RR, MAP, pulmonary infection, D-dimer, PaO₂/FiO₂, Lac, ALB, BUN, APACHE II score and SOFA score (all P < 0.05). Multivariate Logistic regression analysis showed that increased RR, low MAP, pulmonary infection, high Lac and high APACHE II score were independent risk factors for sepsis related ARDS [RR: odds ratio (OR) = 1.167, 95% confidence interval (95%CI) was 1.019-1.336; MAP: OR = 0.962, 95%CI was 0.932-0.994; pulmonary infection: OR = 0.428, 95%CI was 0.189-0.966; Lac: OR = 1.684, 95%CI was 1.036-2.735; APACHE II score: OR = 1.577, 95%CI was 1.202-2.067; all P < 0.05]. Based on the above independent risk factors, a risk nomograph model was established to predict sepsis related ARDS (accuracy was 81.62%, sensitivity was 66.67%, specificity was 89.10%). The predicted values were basically consistent with the measured values, and the AUC was 0.866 (95%CI was 0.819-0.914). CONCLUSIONS Increased RR, low MAP, pulmonary infection, high Lac and high APACHE II score are independent risk factors for sepsis related ARDS. Establishment of a risk nomograph model based on these factors may guide to predict the risk of ARDS in sepsis patients.
Humans ; Retrospective Studies ; Alcoholism ; Prognosis ; Respiratory Distress Syndrome ; Pneumonia ; Sepsis ; Intensive Care Units ; Procalcitonin ; Fibrinogen ; ROC Curve

Multiple plant lineages have independently evolved sex chromosomes and variable kary-otypes to maintain their sessile lifestyles through constant biological innovation.Morus notabilis,a dioecious mulberry species,has the fewest chromosomes among Morus spp.,but the genetic basis of sex determination and karyotype evolution in this species has not been identified.In this study,three high-quality genome assemblies were generated for Morus spp.[including dioecious M.notabilis(male and female)and Morus yunnanensis(female)]with genome sizes of 301-329 Mb and were grouped into six pseudochromosomes.Using a combination of genomic approaches,we found that the putative ancestral karyotype of Morus species was close to 14 protochromosomes,and that sev-eral chromosome fusion events resulted in descending dysploidy(2n=2x=12).We also charac-terized a～6.2-Mb sex-determining region on chromosome 3.Four potential male-specific genes,a partially duplicated DNA helicase gene(named MSDH)and three Ty3_Gypsy long terminal repeat retrotransposons(named MSTG1/2/3),were identified in the Y-linked area and considered to be strong candidate genes for sex determination or differentiation.Population genomic analysis showed that Guangdong accessions in China were genetically similar to Japanese accessions of mul-berry.In addition,genomic areas containing selective sweeps that distinguish domesticated mul-berry from wild populations in terms of flowering and disease resistance were identified.Our study provides an important genetic resource for sex identification research and molecular breeding in mulberry.

Duchenne muscular dystrophy (DMD) is a serious and progressive hereditary muscle disease. The DMD gene mutation on the X chromosome causes the loss of dystrophin, causing progressive muscle weakness and muscular atrophy. Most patients die for heart and lung failure. Current gene therapy methods are mainly aimed at restoring the expression of dystrophin, including read-through therapy, exon skipping therapy, vector-mediated gene replacement therapy and gene editing therapy. This article reviews the mechanisms of these different treatments and important advances in clinical research, and analyzes the challenges and application prospects of these treatments.

Objective:To explore the status quo of perceived responses to capitalization attempts and work flow of clinical nurses, and analyze the correlation between them.Methods:Using the convenient sampling method, a total of in some Class Ⅲ Grade A hospitals of Hangzhou City 567 clinical nurses from three Class Ⅲ Grade A hospitals in Hangzhou were selected as research objects from June to December 2019. Nurse Work Flow Questionnaire (NWF) and Chinese version of Perceived Responses To Capitalization Attempts Scale (PRCA) were used to investigate and to analyze the relationship between perceived responses to capitalization attempts and work flow of clinical nurses. In this study, a total of 567 questionnaires were issued and 551 valid questionnaires were returned, with a recovery rate of 97.18%.Results:The total score of PRCA of 551 clinical nurses was (52.74±8.96) , the total score of NWF for clinical nurses was (112.26±23.42) . Pearson correlation analysis results showed that active construction score of clinical nurses was positively correlated with the score of all dimensions of Nurse Work Flow Questionnaire, while clinical passive construction, passive destruction and active destruction of nurses were negatively correlated with scores of each dimension of Nurse Work Flow Questionnaire ( P<0.05) . After controlling for general demographic data, results of the hierarchical regression of influencing factors for work flow of clinical nurses showed that the active construction of perceived responses to capitalization attempts positively affected the clinical nurses' work flow experience, while passive construction, passive destruction and active destruction all had negative effects on clinical nurses' work flow experience, which could explain 29.1% of the variance of "work flow" variable. Conclusions:Nursing managers should actively improve the active construction response methods in perceived responses to capitalization attempts of clinical nurses and avoid passive construction, active destruction, passive destruction and other response methods, so as to enhance sense of work flow of clinical nurses and improve quality of clinical nursing.

Objective:To explore the effect and mechanism of astaxanthin on acute kidney injury in rats with full-thickness burns.Methods:Forty-eight male Sprague Dawley rats of 8 to 10 weeks were divided into sham injury group, simple burn group, burn+ vehicle group, burn+ low-dose astaxanthin group, burn+ medium-dose astaxanthin group, and burn+ high-dose astaxanthin group according to the random number table, with 8 rats in each group. The back skin of rats in sham injury group were immersed in warm water of 20 ℃ for 15 s to simulate burn injury, and the back skin of rats in the other 5 groups were immersed in boiled water of 100 ℃ for 15 s to inflict full-thickness burn of 30% total body surface area. Fluid resuscitation was performed in rats in the 5 groups except of sham injury group immediately and 6 h after injury. At 30 min after injury, the rats in sham injury group and simple burn group were injected with 1 mL/kg normal saline via tail vein, rats in burn+ vehicle group were injected with 1 mL/kg astaxanthin solvent via tail vein, and rats in burn+ low-dose astaxanthin group, burn+ medium-dose astaxanthin group, and burn+ high-dose astaxanthin group were respectively injected with 5, 10, 20 mg/kg astaxanthin solution of 5, 10, 20 mg/mL via tail vein. The renal tissue was collected at post injury hour (PIH) 48, and hematoxylin eosin staining was used for histopathological observation and renal tubular injury score. At PIH 48, the venous blood was collected for detecting serum creatinine level through blood biochemical analyzer, and blood urea nitrogen (BUN) level was detected by enzyme-linked immunosorbent assay. The renal tissue was collected to detect the mRNA expressions of myeloperoxidase (MPO), interleukin-1β (IL-1β), and IL-6 by real-time fluorescent quantitative reverse transcription polymerase chain reaction method, and the protein expressions of Toll like receptor 4 (TLR4), phosphorylated nuclear factor kappa B (p-NF-кB) p65, and heme oxygenase 1 (HO-1) were detected by Western blotting. Besides, the expression of HO-1 in renal tissue was detected by immunofluorescence method. Data were statistically analyzed with Kruskal-Wallis H test, Dunn-Sidák correction, one-way analysis of variance, and Bonferroni method. Results:(1) At PIH 48, there were no inflammatory cell infiltrating and degeneration or necrosis of cells in renal tissue of rats in sham injury group, and the structure of renal tubules was intact. The renal tubules of burn rats in each group showed injury manifestation of separation between epithelial cell and basement membrane, and vacuole cells and lysate protein aggregation. The injury degree of renal tissue of rats in burn+ high-dose astaxanthin group was obviously decreased compared with that in simple burn group. (2) At PIH 48, compared with that of sham injury group, the renal tubular damage scores of rats in simple burn group, burn+ vehicle group, burn+ low-dose astaxanthin group, and burn+ medium-dose astaxanthin group were significantly increased ( P<0.05 or P<0.01). Compared with those of simple burn group and burn+ vehicle group, the renal tubular damage scores of rats in burn+ medium-dose astaxanthin group and burn+ high-dose astaxanthin group were significantly decreased ( P<0.05 or P<0.01). Compared with that of burn+ low-dose astaxanthin group, the renal tubular damage score of rats in burn+ high-dose astaxanthin group was significantly decreased ( P<0.01). (3) At PIH 48, the level of serum creatinine of rats in sham injury group was (2.42±0.06) mg/L, which was significantly lower than (6.11±0.11), (6.48±0.08), (5.79±0.09), (4.03±0.12) mg/L of simple burn group, burn+ vehicle group, burn+ low-dose astaxanthin group, and burn+ medium-dose astaxanthin group ( P<0.05 or P<0.01). The level of BUN of rats was (21.9±1.3) mmol/L in sham injury group, significantly lower than (32.1±7.4) mmol/L of simple burn group and (30.2±4.8) mmol/L of burn+ vehicle group ( P<0.05 or P<0.01). At PIH 48, compared with those of simple burn group and burn+ vehicle group, the levels of serum creatinine and BUN of (16.0±2.9) mmol/L in burn+ medium-dose astaxanthin group, serum creatinine of (3.02±0.08) mg/L and BUN of (14.5±2.9) mmol/L in burn+ high-dose astaxanthin group, and serum creatinine of (22.8±5.5) mmol/L of rats in burn+ low-dose astaxanthin group were significantly decreased ( P<0.05 or P<0.01). At PIH 48, compared with those of burn+ low-dose astaxanthin group, the levels of serum creatinine and BUN of burn+ high-dose astaxanthin group and serum creatinine of burn+ medium-dose group were obviously decreased ( P<0.05 or P< 0.01). (4) At PIH 48, compared with those of sham injury group, the mRNA expressions of MPO, IL-1β, and IL-6 in renal tissue of rats in simple burn group, burn+ vehicle group, burn+ low-dose astaxanthin group, and burn+ medium dose astaxanthin group, and the mRNA expressions of IL-1β and IL-6 in renal tissue of rats in burn+ high-dose astaxanthin group were obviously increased ( P<0.01). Compared with those of simple burn group and burn+ vehicle group, the mRNA expressions of MPO, IL-1β, and IL-6 in renal tissue of rats were significantly decreased in burn+ low-dose astaxanthin group, burn+ medium-dose astaxanthin group, and burn+ high-dose astaxanthin group ( P<0.01). Compared with those of burn+ low-dose astaxanthin group, the mRNA expressions of MPO, IL-1β, and IL-6 in renal tissue of rats were significantly decreased in burn+ medium-dose astaxanthin group and burn+ high-dose astaxanthin group ( P<0.01). The mRNA expressions of MPO, IL-1β, and IL-6 in renal tissue of rats in burn+ high-dose astaxanthin group were significantly decreased compared with those of burn+ medium-dose astaxanthin group ( P<0.01). (5) At PIH 48 h, compared with those of sham injury group, the protein expressions of TLR4 and p-NF-кB p65 in renal tissue of rats in simple burn group, burn+ vehicle group, burn+ low-dose astaxanthin group, and burn+ high-dose astaxanthin group were obviously increased ( P<0.01). Compared with those of simple burn group, the protein expressions of TLR4 and p-NF-кB p65 in renal tissue of rats in burn+ low-dose astaxanthin group, burn+ medium dose astaxanthin group, and burn+ high-dose astaxanthin group were significantly decreased ( P<0.01). (6) The results of Western blotting combined with immunofluorescence method showed that compared with that of sham injury group, the protein expression of HO-1 in renal tissue of rats in burn+ vehicle group, burn+ low-dose astaxanthin group, burn+ medium-dose astaxanthin group, and burn+ high-dose astaxanthin group were significantly increased at PIH 48 ( P<0.01), and the protein expression of HO-1 in renal tissue of rats in burn+ medium-dose astaxanthin group and burn+ high-dose astaxanthin group was significantly increased compared with that of simple burn group ( P<0.01). Conclusions:Astaxanthin can attenuate the structural damage and functional decline of renal tissue and regulate the release of injury-related inflammatory factors, thus to protect the rats from acute kidney injury after burn. The HO-1/TLR4/NF-кB signaling pathway is the main regulatory mechanism of astaxanthin to achieve anti-inflammation-based renoprotection.

Given the increasing exploitation of antibodies in different contexts such as molecular diagnostics and therapeutics, it would be beneficial to unravel properties of antigen-antibody interaction with modeling of computational protein-protein docking, especially, in the absence of a cocrystal structure. However, obtaining a native-like antigen-antibody structure remains challenging due in part to failing to reliably discriminate accurate from inaccurate structures among tens of thousands of decoys after computational docking with existing scoring function. We hypothesized that some important physicochemical and energetic features could be used to describe antigen-antibody interfaces and identify native-like antigen-antibody structure. We prepared a dataset, a subset of Protein-Protein Docking Benchmark Version 4.0, comprising 37 nonredundant 3D structures of antigen-antibody complexes, and used it to train and test multivariate logistic regression equation which took several important physicochemical and energetic features of decoys as dependent variables. Our results indicate that the ability to identify native-like structures of our method is superior to ZRANK and ZDOCK score for the subset of antigen-antibody complexes. And then, we use our method in workflow of predicting epitope of anti-Ebola glycoprotein monoclonal antibody-4G7 and identify three accurate residues in its epitope.

Wound healing is a complex and sequential biological process involving various cells and factors under body′s regulation. Appropriate interventions play positive roles in promoting effective wound healing and improving healing quality. In the clinical practice, there are many new instruments, dressings, and drugs developed for wound care, including antibacterial dressings, wet dressings, precise debridement, negative pressure wound therapy, cytokines/growth factors, and dermal substitutes, which provide revolutionary means for wound treatment. This article summarizes the effective or mature methods in wound care, providing theoretical and practical basis for choosing appropriate treatment methods in different stages of wound.

There are many factors that may affect the microenvironment of acute and chronic wounds.This article reviews the relationship between temperature factor in the external microenvironment of wound surface and wound healing.The temperature changes in different types and stages of wounds are closely related to the wound healing status.Therefore,wound temperature monitoring provides timely,reliable,and non-invasive method in the evaluation of wound status.As low temperature affects the physiological state of wound,relieving the low temperature state and maintaining normal temperature of the microenvironment of wound can promote wound healing.Further research is needed on the wound repair related effector cell proliferation and the mechanism of regulatory function to determine the optimal constant temperature and heat treatment duration needed for wound healing.