italic>Candida albicans (C. albicans) stands as the primary opportunistic fungal pathogen responsible for fungal infections. The formation of biofilms constitutes a key virulence trait of C. albicans and a pivotal factor in drug resistance. Consequently, the development of antifungal drugs possessing biofilm inhibitory properties holds importance in the treatment of fungal infectious diseases. This study conducted in-depth research of the novel biofilm inhibitor named 1-(cyclopentylamino)-3-(4-(2,4,4-trimethylpentan-2-yl)phenoxy)propan-2-ol (IMB-H12). IMB-H12 showed good inhibitory activity on the formation of biofilms and a certain scavenging effect on mature biofilms. Preliminary research on the mechanism of action has found that IMB-H12 can inhibit the transformation from yeast to hyphal phase, inhibit the formation of mycelium, and reduce the adhesion activity and hydrophobicity of Candida albicans. IMB-H12 could also induce changes in the content of cell wall components, downregulate the expression of multiple genes related to adhesion and hyphal formation. Therefore, further research on this compound is expected to discover new lead compounds with antifungal activity.

In this study,a method for detecting heavy metal ions using potentiometric sensor and voltammetric sensor was proposed.By exploiting the complementary advantages of potentiometric and voltammetric electrochemical sensor,the traditional electrochemical electrode without special material preparation and modification could be used for the wide range and accurate detection of heavy metal ions in actual water samples.During detection,the concentration of target ion was measured by a potentiometric electrochemical sensor to determine the concentration range.The amperometric electrochemical sensor was then used for calibration and accurate measurement in the appropriate concentration range.Taking copper ion(Cu2+)as an example,the prepared Cu2+water sample and the actual water sample were tested.First,the copper ion selective electrode was used to determine the concentration range of Cu2+in the sample.Then,based on the gold electrode in different concentration range(0.86-100 μg/L and 100-300 μg/L)using two different optimization parameter settings to calibrate the electrochemical sensor and measure,the test results had a good correlation with those by professional water quality testing institutions.The recoveries ranged from 86.7%to 103.0%.The experimental results showed that the combination of potential sensor and current sensor could improve the accuracy of detection of heavy metal ions in water samples by electrochemical sensor.

Background/Aims: Ubiquitination is widely involved in the progression of hepatocellular carcinoma (HCC) by regulating various cellular processes. However, systematic strategies for screening core ubiquitin-related genes, clarifying their functions and mechanisms, and ultimately developing potential therapeutics for patients with HCC are still lacking. Methods: Cox and LASSO regression analyses were performed to construct a ubiquitin-related gene prediction model for HCC. Loss- and gain-of-function studies, transcriptomic and metabolomics analysis were used to explore the function and mechanism of UBE2S on HCC cell glycolysis and growth. Results: Based on 1,423 ubiquitin-related genes, a four-gene signature was successfully constructed to evaluate the prognosis of patients with HCC. UBE2S was identified in this signature with the potential to predict the survival of patients with HCC. E2F2 transcriptionally upregulated UBE2S expression by directly binding to its promoter. UBE2S positively regulated glycolysis in a HIF-1α-dependent manner, thus promoting the proliferation of HCC cells. Mechanistically, UBE2S enhanced K11-linkage polyubiquitination at lysine residues 171 and 196 of VHL independent of E3 ligase, thereby indirectly stabilizing HIF-1α protein levels by mediating the degradation of VHL by the proteasome. In particular, the combination of cephalomannine, a small molecule compound that inhibits the expression of UBE2S, and PX-478, an inhibitor of HIF-1α, significantly improved the anti-tumor efficacy. Conclusions UBE2S is identified as a key biomarker in HCC among the thousands of ubiquitin-related genes and promotes glycolysis by E3 enzyme-independent ubiquitination, thus serving as a therapeutic target for the treatment of HCC.

Humans ; Arthroplasty, Replacement, Knee/adverse effects* ; Arthritis, Rheumatoid/surgery* ; Risk Factors ; Patients ; Arthroplasty, Replacement, Hip/adverse effects*

BACKGROUND: Currently, a significant number of miners are involved in mining operations at the Gejiu tin mine in Yunnan. This occupational setting is associated with exposure to dust particles, heavy metals, polycyclic aromatic hydrocarbons, and radioactive radon, thereby significantly elevating the risk of lung cancer. This study aims to investigate the involvement of leptin-mediated extracellular regulated protein kinase (ERK) signaling pathway in the malignant transformation of rat alveolar type II epithelial cells induced by Yunnan tin mine dust. METHODS: Immortalized rat alveolar cells type II (RLE-6TN) cells were infected with Yunnan tin mine dust at a concentration of 200 μg/mL for nine consecutive generations to establish the infected cell model, which was named R₂₀₀ cells. The cells were cultured normally, named as R cells. The expression of leptin receptor in both cell groups was detected using the Western blot method. The optimal concentration of leptin and mitogen-activated protein kinase kinase (MEK) inhibitor (U0126) on R₂₀₀ cells was determined using the MTT method. Starting from the 20th generation, the cells in the R group were co-cultured with leptin, while the cells in the R₂₀₀ group were co-cultured with the MEK inhibitor U0126. The morphological alterations of the cells in each group were visualized utilizing hematoxylin-eosin staining. Additionally, concanavalin A (ConA) was utilized to detect any morphological differences, and an anchorage-independent growth assay was conducted to assess the malignant transformation of the cells. The changes in the ERK signaling pathway in epithelial cells after the action of leptin were detected using the Western blot method. RESULTS: Both the cells in the R group and R₂₀₀ group express leptin receptor OB-R. Compared to the R₂₀₀ group, the concentration of leptin at 100 ng/mL shows the most significant pro-proliferation effect. The proliferation of R₂₀₀ cells infected with the virus is inhibited by 30 μmol/L U0126, and a statistically significant divergence was seen when compared to the control group (P<0.05). Starting from the 25th generation, the cell morphology of the leptin-induced R₂₀₀ group (R₂₀₀L group) underwent changes, leading to malignant transformation observed at the 30th generation. The characteristics of malignant transformation became evident by the 40th generation in the R₂₀₀L group. In contrast, the other groups showed agglutination of P40 cells, and the speed of cell aggregation increased with an increase in ConA concentration. Notably, the R₂₀₀L group exhibited faster cell aggregation compared to the U0126-induced R₂₀₀ (R₂₀₀LU) group. Additionally, the cells in the R₂₀₀L group were capable of forming clones starting from P30, with a colony formation rate of 2.25‰±0.5‰. However, no clonal colonies were observed in the R₂₀₀LU group and R₂₀₀ group. The expression of phosphorylated extracellular signal-regulated kinase (pERK) was enhanced in cells of the R₂₀₀L group. However, when the cells in the R₂₀₀L group were treated with U0126, a blocking agent, the phosphorylation level of pERK decreased. CONCLUSIONS Leptin can promote the malignant transformation of lung epithelial cells infected by mine dust, and the ERK signaling pathway may be necessary for the transformation of alveolar type II epithelial cells induced by Yunnan tin mine dust.
Rats ; Animals ; Alveolar Epithelial Cells/pathology* ; Dust ; Tin/adverse effects* ; Lung Neoplasms/pathology* ; Leptin/adverse effects* ; Receptors, Leptin ; China ; Signal Transduction ; Epithelial Cells/pathology* ; Mitogen-Activated Protein Kinase Kinases/adverse effects*

Objective:To explore the risk factors of primary acute mesenteric venous thrombosis (AMVT) in plateau area.Methods:Data of 54 primary AMVT cases admitted to the People's Hospital of Tibet Autonomous Region between Jan 2015 and Jul 2021 were retrospectively analyzed. There were 42 males and 12 females, aged from 29-79 years. One hundred and ninty matched volunteers severed as control. Logistic multivariate regression analysis was used to screen out independent risk factors. The receiver operating characteristic (ROC) curve and the area under the curve are used to evaluate the value of each indicator and model prediction.Results:Univariate analysis showed that the two groups were significantly different in gender, smoking history, drinking history, and hemoglobin concentration ( P<0.05); there was no significant difference in age, altitude of residence, uric acid and BMI ( P>0.05). Logistic multivariate regression analysis showed that male ( OR=2.466, 95% CI: 1.166-5.212, P=0.018), elevated hemoglobin levels ( OR=2.761, 95% CI: 1.411-5.403, P=0.003) were independent risk factors for primary AMVT. The area under the ROC curve of the two predictors and prediction model are 0.639 (95% CI: 0.559-0.719), 0.650 (95% CI: 0.563-0.737), 0.697 (95% CI: 0.618-0.776). Conclusion:Male and elevated hemoglobin levels are independent risk factors for primary AMVT in plateau areas.

Objective: To explore the clinical effects of three-dimensional printed preformed titanium mesh combined with latissimus dorsi muscle flap free transplantation in the treatment of wounds with skull defect after radical surgery of squamous cell carcinoma in the vertex. Methods: A retrospective observational study was conducted. From January 2010 to December 2019, 5 patients with squamous cell carcinoma in the vertex accompanied with skull invasion who met the inclusion criteria were admitted to the Department of Burns and Plastic Surgery of the Second Affiliated Hospital of Air Force Medical University, including four males and one female, aged 50 to 65 years. The original lesion areas ranged from 5 cm×4 cm to 15 cm×8 cm. The titanium mesh was prefabricated via three-dimensional technic based on the result the scope of skull resection predicted with computerized tomography three-dimensional reconstruction before surgery. During the first stage, the soft tissue defect area of scalp (8 cm×7 cm to 18 cm×11 cm) after tumor enlargement resection was repaired with the preformed titanium mesh, and the titanium mesh was covered with latissimus dorsi muscle flap, with area of 10 cm×9 cm to 20 cm×13 cm. The thoracodorsal artery/vein was anastomosed with the superficial temporal artery/vein on one side. The muscle ends in the donor site were sutured together or performed with transfixion, and then the skin on the back were covered back to the donor site. On the 10th day after the first-stage surgery, the second-stage surgery was performed. The thin intermediate thickness skin graft was taken from the anterolateral thigh to cover the latissimus dorsi muscle flap. The duration and intraoperative blood loss of first-stage surgery were recorded. The postoperative muscle flap survival after the first-stage surgery and skin graft survival after the second-stage surgery was observed. The occurrence of complications, head appearance, and recurrence of tumor were followed up. Results: The average first-stage surgery duration of patients was 12.1 h, and the intraoperative blood loss was not more than 1 200 mL. The muscle flaps in the first-stage surgery and the skin grafts in the second-stage surgery all survived well. During the follow-up of 6-18 months, no complications such as exposure of titanium mesh or infection occurred, with good shape in the recipient sites in the vertex, and no recurrence of tumor. Conclusions: Three-dimensional printed preformed titanium mesh combined with latissimus dorsi muscle flap free transplantation and intermediate thickness skin graft cover is an effective and reliable method for repairing the wound with skull defect after extended resection of squamous cell carcinoma in the vertex. This method can cover the wound effectively as well as promote both recipient and donor sites to obtain good function and appearance.
Carcinoma, Squamous Cell/surgery* ; Female ; Humans ; Male ; Perforator Flap ; Reconstructive Surgical Procedures/methods* ; Scalp/surgery* ; Skin Transplantation ; Skull/surgery* ; Soft Tissue Injuries/surgery* ; Superficial Back Muscles/surgery* ; Surgical Mesh ; Titanium ; Treatment Outcome

The gross specimens and tissue slices used for traditional experimental pathology curriculum are fragile, and some specimens or slices are difficult to be supplemented. Besides, the classroom and schedule for experimental pathology teaching are inflexible. Therefore, the teaching effects for experimental pathology course are limited. The development of digital technology has promoted the teaching reform of medical experimental curriculum. We have digitalized the gross specimens and tissue slices to preserve and expand the samples, and constructed pathological sample repository containing both physical samples and digital samples. Furthermore, we have established a platform for remote access, and thus improved the flexibility and autonomy of study for experimental pathology curriculum. Additionally, we have integrated clinical information of the teaching samples, and interpreted the specimens with the assistance of two-dimensional code technology and voice broadcast technology, to realize human-computer interactive learning. The questionnaire shows that the application of pathological sample repository in experimental teaching has improved student learning effect and recognition.

Objective: To observe changes in the molecular expression of the NLR Family Pyrin Domain Containing Protein 3 (NLRP3) pathway in depressed rats after treatment with Xiaoyaosan, and identify the regu-latory mechanism of this compound. Methods: Male Sprague-Dawley rats were randomly divided into five groups with 12 rats in each group, including the control group, model group, Fluoxetine group, Xiaoyaosan group, and MCC950 group. A depression model was generated by chronic immobilization stress (induced by 3 h of restraint immo-bilization every day), and the drugs were administered at the same time in each group for 21 days. The effects of Xiaoyaosan on behavioral changes of depressed rats were observed through macroscopic characterization, body mass, open field experiments, and a sucrose preference test. The mRNA and protein expression of the NLRP3 signaling pathway was examined by fluorescence real-time quantitative PCR and Western blot assays. Results: The Xiaoyaosan group, Fluoxetine group, and MCC950 group rats showed improved depressive behavior and an increased weight of sucrose water consumption. The protein and mRNA expression levels of NLRP3, Caspase-1, and IL-1β were also decreased in the Fluoxetine, Xiaoyaosan, and MCC950 groups. Conclusion: NLRP3, Caspase-1, and IL-1β protein and mRNA expression levels were increased in the cortex of depressed rats, while Xiaoyaosan protected cortical tissue in these rats by decreasing NLRP3, Caspase-1, and IL-1βprotein and mRNA expression.

Objective:To investigate the pathological characteristics and the clinical significance of novel coronavirus (2019-nCoV)-infected pneumonia (termed by WHO as coronavirus disease 2019, COVID-19).Methods:Minimally invasive autopsies from lung, heart, kidney, spleen, bone marrow, liver, pancreas, stomach, intestine, thyroid and skin were performed on three patients died of novel coronavirus pneumonia in Chongqing, China. Hematoxylin and eosin staining (HE), transmission electron microcopy, and histochemical staining were performed to investigate the pathological changes of indicated organs or tissues. Immunohistochemical staining was conducted to evaluate the infiltration of immune cells as well as the expression of 2019-nCoV proteins. Real time PCR was carried out to detect the RNA of 2019-nCoV.Results:Various damages were observed in the alveolar structure, with minor serous exudation and fibrin exudation. Hyaline membrane formation was observed in some alveoli. The infiltrated immune cells in alveoli were majorly macrophages and monocytes. Moderate multinucleated giant cells, minimal lymphocytes, eosinophils and neutrophils were also observed. Most of infiltrated lymphocytes were CD4-positive T cells. Significant proliferation of type Ⅱ alveolar epithelia and focal desquamation of alveolar epithelia were also indicated. The blood vessels of alveolar septum were congested, edematous and widened, with modest infiltration of monocytes and lymphocytes. Hyaline thrombi were found in a minority of microvessels. Focal hemorrhage in lung tissue, organization of exudates in some alveolar cavities, and pulmonary interstitial fibrosis were observed. Part of the bronchial epithelia were exfoliated. Coronavirus particles in bronchial mucosal epithelia and type Ⅱ alveolar epithelia were observed under electron microscope. Immunohistochemical staining showed that part of the alveolar epithelia and macrophages were positive for 2019-nCoV antigen. Real time PCR analyses identified positive signals for 2019-nCoV nucleic acid. Decreased numbers of lymphocyte, cell degeneration and necrosis were observed in spleen. Furthermore, degeneration and necrosis of parenchymal cells, formation of hyaline thrombus in small vessels, and pathological changes of chronic diseases were observed in other organs and tissues, while no evidence of coronavirus infection was observed in these organs.Conclusions:The lungs from novel coronavirus pneumonia patients manifest significant pathological lesions, including the alveolar exudative inflammation and interstitial inflammation, alveolar epithelium proliferation and hyaline membrane formation. While the 2019-nCoV is mainly distributed in lung, the infection also involves in the damages of heart, vessels, liver, kidney and other organs. Further studies are warranted to investigate the mechanism underlying pathological changes of this disease.