CircPVT1 promotes migration and invasion by regulating miR-490-5p/HAVCR2 axis in osteosarcoma cells.

Circular RNAs (circRNAs) play an important role in the progression of osteosarcoma. However, the precise function of circPVT1 in osteosarcoma remains elusive. This study aims to explore the molecular mechanism underlying the involvement of circPVT1 in osteosarcoma cells. We quantified circPVT1 expression using qRT-PCR in both control and osteosarcoma cell lines. To investigate the roles of circPVT1, miR-490-5p and HAVCR2 in vitro, we separately conducted overexpression and inhibition experiments for circPVT1, miR-490-5p and HAVCR2 in HOS and U2OS cells. Cell migration was assessed through wound healing and transwell migration assays, and invasion was measured via the Matrigel invasion assay. To elucidate the regulatory mechanism of circPVT1 in osteosarcoma, a comprehensive approach was employed, including fluorescence in situ hybridization, qRT-PCR, Western blot, bioinformatics, dual-luciferase reporter assay and rescue assay. CircPVT1 expression in osteosarcoma cell lines surpassed that in control cells. The depletion of circPVT1 resulted in a notable reduction in the in vitro migration and invasion of osteosarcoma cells. Mechanism experiments revealed that circPVT1 functioned as a miR-490-5p sequester, and directly targeted HAVCR2. Overexpression of miR-490-5p led to a significant attenuation of migration and invasion of osteosarcoma cells, whereas HAVCR2 overexpression had the opposite effect, promoting these abilities. Additionally, circPVT1 upregulated HAVCR2 expression via sequestering miR-490-5p, thereby orchestrating the migration and invasion in osteosarcoma cells. CircPVT1 orchestrates osteosarcoma migration and invasion by regulating the miR-490-5p/HAVCR2 axis, underscoring its potential as a promising therapeutic target for osteosarcoma.

Primary cilia abnormalities participate in the occurrence of spontaneous abortion through TGF-ß/SMAD2/3 signaling pathway.

Spontaneous abortion is the most common complication in early pregnancy, the exact etiology of most cases cannot be determined. Emerging studies suggest that mutations in ciliary genes may be associated with progression of pregnancy loss. However, the involvement of primary cilia on spontaneous abortion and the underlying molecular mechanisms remains poorly understood. We observed the number and length of primary cilia were significantly decreased in decidua of spontaneous abortion in human and lipopolysaccharide (LPS)-induced abortion mice model, accompanied with increased expression of proinflammatory cytokines interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α. The length of primary cilia in human endometrial stromal cell (hESC) was significantly shortened after TNF-α treatment. Knocking down intraflagellar transport 88 (IFT88), involved in cilia formation and maintenance, promoted the expression of TNF-α. There was a reverse regulatory relationship between cilia shortening and TNF-α expression. Further research found that shortened cilia impair decidualization in hESC through transforming growth factor (TGF)-ß/SMAD2/3 signaling. Primary cilia were impaired in decidua tissue of spontaneous abortion, which might be mainly caused by inflammatory injury. Primary cilia abnormalities resulted in dysregulation of TGF-ß/SMAD2/3 signaling transduction and decidualization impairment, which led to spontaneous abortion.

Characterization and gene expression analysis reveal universal stress proteins respond to abiotic stress in Gossypium hirsutum.

BACKGROUND: Universal stress proteins (USPs) are a class of stress-induced proteins that play a crucial role in biotic and abiotic stress responses. These proteins have previously been reported to participate directly in responses to various stress and protect plants against unfavorable environmental conditions. However, there is limited research on USPs in cotton, and systematic characterization of USPs in Gossypium species is lacking. RESULTS: In the present study, the USP genes in Gossypium hirsutum were systematically identified and classified into six distinct subfamilies. The expansion of USPs in Gossypium species is mainly caused by dispersed duplication and whole genome duplication. Notably, the USPs that have expanded through allotetraploidization events are highly conserved in the allotetraploid species. The promoter regions of GhUSPs contain a diverse range of cis-acting elements associated with stress response. The RNA-Seq analysis and RT-qPCR assays revealed a significant induction of numerous GhUSPs expressions in response to various abiotic stresses. The co-expression network of GhUSPs revealed their involvement in stress response. CONCLUSIONS: This study systematically analyzed the biological characteristics of GhUSPs and their response to abiotic stress. These findings serve as a theoretical basis for facilitating the breeding of cotton varieties in future research.

Theoretical derivation and application of empirical Harvey scatter model.

Starting from the Rayleigh-Rice perturbation theory, this paper derives the empirical Harvey scatter model and ABg scatter model applied extensively in optical analysis software packages and verifies the shift-invariant behavior of the scattered radiance in direction cosine space. Using data obtained from multi-wavelength laser scatterometer on carbon nanotube black coating and pineblack coating, we establish the polynomial model based on the sine of the scattering angle plus the sine of the specular reflection angle, i.e., sin θs+sin θ0 and the dual-Harvey model based on sin θs-sin θ0 , respectively. The models are in good accordance with the experimental data and further extend the valid range of empirical models.

Characterization of ovarian progenitor cells for their potential to generate steroidogenic theca cells in vitro.

In brief: Progenitor cells with ovulation-related tissue repair activity were identified with defined markers (LGR5, EPCR, LY6A, and PDGFRA), but their potentials to form steroidogenic cells were not known. This study shows that the cells can generate progenies with different steroidogenic activities. Abstract: Adult mammalian ovaries contain stem/progenitor cells necessary for folliculogenesis and ovulation-related tissue rupture repair. Theca cells are recruited and developed from progenitors during the folliculogenesis. Theca cell progenitors were not well defined. The aim of current study is to compare the potentials of four ovarian progenitors with defined markers (LY6A, EPCR, LGR5, and PDGFRA) to form steroidogenic theca cells in vitro. The location of the progenitors with defined makers was determined by immunohistochemistry and immunofluorescence staining of ovarian sections of adult mice. Different progenitor populations were purified by magnetic-activated cell sorting (MACS) and/or fluorescence-activated cell sorting (FACS) techniques from ovarian cell preparation and were tested for their abilities to generate steroidogenic theca cells in vitro. The cells were differentiated with a medium containing LH, ITS, and DHH agonist for 12 days. The results showed that EPCR+ and LGR5+ cells primarily distributed along the ovarian surface epithelium (OSE), while LY6A+ cells distributed in both the OSE and parenchyma. However, PDGFRA+ cells were exclusively located in interstitial compartment. When the progenitors were purified by these markers and differentiated in vitro, LY6A+ and PDGFRA+ cells formed steroidogenic cells expressing both CYP11A1 and CYP17A1 and primarily producing androgens, showing characteristics of theca-like cells, while LGR5+ cells generated steroidogenic cells devoid of CYP17A1 expression and androgen production, showing a characteristic of progesterone-producing cells (granulosa- or lutea-like cells). In conclusion, progenitors from both OSE and parenchyma of adult mice are capable of generating steroidogenic cells with different steroidogenic capacities, showing a possible lineage preference.

Rapid identifying of COX-2 inhibitors from turmeric (Curcuma longa) by bioaffinity ultrafiltration coupled with UPLC-Q Exactive-Orbitrap-MS and zebrafish-based in vivo validation.

Turmeric (Curcuma longa), a typical source with recognized anti-inflammatory activity, is one such medicine-food homology source, yet its anti-inflammatory mechanisms and specific component combinations remain unclear. In this study, a net fishing method combining bio-affinity ultrafiltration and ultra-high performance liquid chromatography-mass spectrometry (AUF-LC/MS) was employed and 13 potential COX-2 inhibitors were screened out from C. longa. 5 of them (C1, 17, 20, 22, 25) were accurately isolated and identified. Initially, their IC50 values were measured (IC50 of C1, 17, 20, 22 and 25 is 55.08, 48.26, 29.13, 111.28 and 150.48 µM, respectively), and their downregulation of COX-2 under safe concentrations (400, 40, 120, 50 and 400 µM for C1, 17, 20, 22 and 25, respectively) was confirmed on RAW 264.7 cells. Further, in transgenic zebrafish (Danio rerio), significant anti-inflammatory activity at safe concentrations (15, 3, 1.5, 1.5 and 3 µg/mL for C1, 17, 20, 22 and 25, respectively) were observed in a dose-dependent manner. More importantly, molecular docking analysis further revealed the mode of interaction between them and the key active site residues of COX-2. This study screened out and verified unreported COX-2 ligands, potentially accelerating the discovery of new bioactive compounds in other functional foods.

Associations between adverse childhood experiences and pain in middle-aged and older adults: findings from the China Health and Retirement Longitudinal Study.

OBJECTIVE: Adverse childhood experiences (ACEs) have been associated with a range of adverse health outcomes, with pain being potentially one of them. This population-based cross-sectional study aimed to investigate the associations between Adverse Childhood Experiences (ACEs) and pain in Chinese adults and evaluate whether physical activity and demographic and socioeconomic characteristics modify this associations. METHODS: Cross-sectional data from the China Health and Retirement Longitudinal Study (CHARLS), were utilized in this study. A total of 9923 respondents with information on 12 ACE indicators and 15 self-reported body pains were included. Logistic regression models were used to assess associations of the ACEs and pain. Modification of the associations by physical activity, demographic and socioeconomic characteristics was assessed by stratified analyses and tests for interaction. RESULTS: Among the 9923 individuals included in the primary analyses, 5098 (51.4%) males and the mean (SD) age was 61.18 (10·.44) years. Compared with individuals with 0 ACEs, those who with ≥ 5 ACEs had increased risk of single pains and multiple pain. A dose-response association was found between the number of ACEs and the risk of pain (e.g. neck pain for ≥ 5 ACEs vs. none: OR, 1.107; 95% CI, 0.903-1.356; p < 0.001 for trend). In the associations of each body pain with each ACE indicator, most ACE indicators were associated with an increased risk of pain. In addition, physical activity, sociodemographic and socioeconomic characteristics, such as age, sex, educational level, area of residence, childhood economic hardship, did not demonstrate a significant modify on the associations between ACEs and pain. CONCLUSIONS: These findings indicate that cumulative ACE exposure is associated with increased odds of self-reported pain in Chinese adults, regardless of adult physical activity, sociodemographic and socioeconomic characteristics.

Weight change patterns across adulthood are associated with the risk of osteoarthritis: a population-based study.

BACKGROUND: Body weight has been recognized as a driving factor of osteoarthritis. Few studies had investigated the association between weight status across adulthood and risk of osteoarthritis (OA). This study investigates the association of weight change patterns across adulthood (lasting at least 25 years) with the risk of OA from the National Health and Nutrition Examination Survey (NHANES) 2013-2018. METHODS: The study assessed the relationship between weight change across adulthood and OA in 7392 individuals aged > 50 spanning a minimum of 25 years. Multivariate linear regression analyses were utilized to detect the association between weight change patterns and self-reported OA. Restricted cubic splines (RCS) were used to examine the nonlinear relationship between absolute weight change and OA risk. RESULTS: From 10 years ago to survey, the risk of OA was 1.34-fold (95% CI 1.07-1.68) in people changed from obese to non-obese, 1.61-fold (95% CI 1.29-2.00) in people change from non-obese to obese, and 1.82-fold (95% CI 1.49-2.22) in stable obese people compared with people who were at stable normal weight. Similar patterns were also observed at age 25 years to baseline and age 25 years to 10 years before the baseline. The dose-response association of RCS found a U-shaped relationship between absolute weight change and OA risk. CONCLUSIONS: The study suggests that weight patterns across adulthood are associated with the risk of OA. These findings stressed important to maintain a normal weight throughout adulthood, especially to prevent ignored weight gain in early adulthood to reduce OA risk later.

Safety Study of Raltitrexed Perfusion in Elderly Patients with Colorectal Cancer and Effect on CEA mRNA in Peritoneal Lavage Fluid.

Background: Intraperitoneal chemotherapy is an effective way to kill free tumor cells in the abdominal cavity. The safety and efficacy of raltitrexed perfusion during radical surgery for elderly patients with colorectal cancer are still unclear. Methods: In accordance with computer-generated random allocation sequences, 116 elderly patients with colorectal cancer who received radical surgery were randomly grouped into the raltitrexed intraperitoneal perfusion group or the saline intraperitoneal perfusion group from January 2020 to December 2021 in the First Affiliated Hospital of Bengbu Medical University. t tests and χ2 tests were used to analyze the difference between the two groups of the clinical characteristics, pathological features, perioperative parameters, and carcinoembryonic antigen mRNA in the peritoneal lavage fluid. Results: No statistically significant differences in postoperative complications after radical surgery were observed between the two groups. No statistically significant differences in peripheral blood indexes were observed between the two groups before surgery or on the first and third days after surgery. One day after radical surgery, the alanine transaminase (54.33 ± 4.93 vs 51.01 ± 5.56) and aspartate transaminase (49.28 ± 4.30 vs 50.99 ± 3.88) in the peripheral blood were higher in the raltitrexed intraperitoneal perfusion group than in the saline intraperitoneal perfusion group. At the same time, no significant difference was found on the third day after surgery. No significant differences in side effects of chemotherapy were observed between the two groups. The positive rate of carcinoembryonic antigen mRNA in the raltitrexed intraperitoneal perfusion group (8.47%) was significantly lower than that in the saline intraperitoneal perfusion group (22.81%) after surgery. Conclusion: Raltitrexed perfusion during radical surgery is safe and feasible for elderly patients with CRC and can reduce the positive rate of carcinoembryonic antigen mRNA in peritoneal lavage fluid, so it can be explored as a treatment option.

Anatomical Comparison of Endoscopic and Microscopic Exposure of the Petroclinal Core Area Through the Extended Middle Skull Base Approach.

OBJECTIVE: To compare the range of endoscopic and microscopic exposure of the petroclival core area through the middle skull base and to observe the corresponding anatomical structures. METHODS: Ten intact adult cadaveric head specimens fixed with formaldehyde were craniotomized through an expanded middle skull base epidural approach on 20 sides. The distance from the greater superficial petrosal nerve to the petrous ridge was measured. When different degrees (1-3 degrees) of the Kawase triangle bone were removed, the exposed anatomical structure was observed, and the exposed core area of the rock slope was measured under an endoscope and microscope. RESULTS: The average distance from the greater superficial petrosal nerve to the petrous ridge was 14.26 mm. During 1 to 2 degrees of bone removal, the petrous segment of the internal carotid artery (ICA) was not exposed, whereas during 3 degrees of bone removal, the petrous segment of the ICA was exposed. At 1 degree of bone removal, 400.62 ± 15.73 mm2 of the area was exposed by endoscopy and 170.87 ± 8.93 mm2 by microscopy, and the abducens nerve was not exposed. However, there was a significant difference between the two areas (P < 0.001). During 2 degrees of bone removal, 689.30 ± 32.06 mm2 of the abducens nerve was exposed by endoscopy, but 366.84 ± 30.30 mm2 of the abducens nerve could not be exposed by microscopy; moreover, there was a significant difference in the area of exposure between the two (P < 0.001). At 3 degrees of bone removal, the endoscopic exposure area was 875.92 ± 31.87 mm2, the microscopic exposure area was 699.26 ± 48.00 mm2, and the abducens nerves were exposed. There were significant differences between the two areas (P < 0.001). However, the difference between the 2-degree endoscopic exposure area and the 3-degree microscopic exposure area was studied by using paired t tests, and there was no difference (P > 0.05). CONCLUSION: When the same degree of the Kawase triangle bone was removed, the extent of endoscopic exposure of the petroclival core area was significantly greater than the extent of microscopic exposure. At 2 degrees of bone removal, an endoscopic application can maximally expose the petroclival core area, thus reducing the probability of exposure damage to the ICA and abductor nerve.

Piezoelectric Active Sensing-Based Pipeline Corrosion Monitoring Using Singular Spectrum Analysis.

Pipelines are an important transportation form in industry. However, pipeline corrosion, particularly that occurring internally, poses a significant threat to safe operations. To detect the internal corrosion of a pipeline, a method utilizing piezoelectric sensors alongside singular spectrum analysis is proposed. Two piezoelectric patches are affixed to the exterior surface of the pipeline, serving the roles of an actuator and a sensor, respectively. During the detection, the signals excited by the actuator are transmitted through the pipeline's wall and are received by PZT2 through different paths, and the corresponding piezoelectric sensor captures the signals. Then, the response signals are denoised by singular spectrum analysis, and the first several wave packets in the response signals are selected to establish a feature for pipeline corrosion detection. At last, the envelope area of the selected packets is calculated as a feature to detect corrosion. To validate the proposed method, corrosion monitoring experiments are performed. The experimental results indicate that the envelope area of the first several wave packets from the response signals, following singular spectrum analysis, can serve as a feature to assess the degree of pipeline corrosion, and the index has a monotonic relationship with the corrosion depth of the pipeline. This method provides an effective way for pipeline corrosion monitoring.

Potential of combined reactor and static composting applications for the removal of heavy metals and antibiotic resistance genes from chicken manure.

Chicken manure (CM) can pose a serious threat to environmental and human health, and need to be managed properly. The compost can effectively treat CM. However, there is limited research on the heavy metals and antibiotic resistance genes (ARGs) during compost CM. In this study, the combined application of reactor and static composting (RSC) was used to produce organic fertilizer of CM (OCM), and heavy metals, ARGs and bacterial community structure was investigated. The results show that RSC could be used to produce OCM, and OCM meet the National organic fertilizer standard (NY/T525-2021). Compared to the initial CM, DTPA-Cu, DTPA-Zn, DTPA-Pb, DTPA-Cr, DTPA-Ni and DTPA-As in OCM decreased by 40.83%, 23.73%, 34.27%, 38.62%, 16.26%, and 43.35%, respectively. RSC decreased the relative abundance of ARGs in CM by 84.06%, while the relative abundance of sul1 and ermC increased. In addition, the relative abundance and diversity of ARGs were mainly influenced by the bacterial community, with Actinobacteria, Firmicutes, and Proteobacteria becoming the dominant phyla during composting, and probably being the main carriers and dispersers of most of the ARGs. Network analyses confirmed that Gracilibacillus, Lactobacillus, Nocardiopsis, Mesorhizobium and Salinicoccus were the main potential hosts of ARGs, with the main potential hosts of sul1 and ermC being Mesorhizobium and Salinicoccus. The passivation and physicochemical properties of heavy metals contribute to the removal of ARGs, with sul1 and ermC being affected by the toal heavy metals. Application of RSC allows CM to produce mature, safe organic fertilizer after 32 d and reduces the risk of rebound from ARGs, but the issues of sul1 and ermC gene removal cannot be ignored.

Enhanced CH4/N2 Separation Efficiency of UiO-66-Br2 through Hybridization with Mesoporous Silica.

Efficient separation of CH4 from N2 is essential for the purification of methane from nitrogen. In order to address this problem, composite materials consisting of rod-shaped SBA-15-based UiO-66-Br2 were synthesized for the purpose of separating a CH4/N2 mixture. The materials were characterized via PXRD, N2 adsorption-desorption, SEM, TEM, FT-IR, and TGA. The adsorption isotherms of CH4 and N2 under standard pressure conditions for the composites were determined and subsequently compared. The study revealed that the composites were formed through the growth of MOF nanocrystals on the surfaces of the SBA-15 matrix. The enhancements in surface area and adsorption capacity of hybrid materials were attributed to the structural modifications resulting from the interactions between surface silanol groups and metal centers. The selectivity of the composites towards a gas mixture of CH4 and N2 was assessed utilizing the Langmuir adsorption equation. The results of the analysis revealed that the U6B2S5/SBA-15 sample exhibited the greatest selectivity for CH4/N2 adsorption compared to the other samples, with an adsorption selectivity parameter (S) of 20.06. Additional research is necessary to enhance the enrichment of methane from CH4/N2 mixtures using SBA-15-based metal-organic framework materials.

Corrosion Inhibition Properties of Corrosion Inhibitors to under-Deposit Corrosion of X65 Steel in CO2 Corrosion Conditions.

Under-deposit corrosion is widely present in the pipelines of oil and gas production, causing significant corrosion damage. In this paper, a novel electrochemical cathodic-polarization method was carried out to accelerate the formation of CaCO3 scale on a X65 steel surface in a simulated solution containing scaling ions. Subsequently, pre-scaled X65 steel was placed in a high temperature and pressure autoclave to conduct corrosion weight-loss experiments and in situ electrochemical measurements. The study mainly compared the corrosion inhibition behavior of four quaternary ammonium salt corrosion inhibitors, pyridinium quaternary salt (BPC), quinolinium quaternary salt (BQC), 8-hydroxyquinolinium quaternary salt (BHQ) and pyridinium (1-chloromethyl naphthalene) quaternary salt (1-CPN), in a simulated oilfield scale under corrosive conditions. The results of the weight-loss experiments demonstrated that the inhibition efficiencies of the corrosion inhibitors from high to low were as follows: 1-CPN < BHQ < BQC < BPC. The in situ electrochemical measurements showed that the immersion time and type of corrosion inhibitor had a pronounced influence on the corrosion and corrosion inhibition behavior of X65 steel with CaCO3 coating. It was also proved using both EIS and PC that 1-CPN shows the best inhibition performance in all. Lastly, the inhibition mechanism of corrosion inhibitors at under-deposit conditions was analyzed via a surface morphology observation of SEM.

Effectiveness and safety of augmentative plating technique in managing nonunion following intramedullary nailing of long bones in the lower extremity: A systematic review and meta-analysis.

PURPOSE: To methodically assess the effectiveness of augmentative plating (AP) and exchange nailing (EN) in managing nonunion following intramedullary nailing for long bone fractures of the lower extremity. METHODS: PubMed, EMBASE, Web of Science, and the Cochrane Library were searched to gather clinical studies regarding the use of AP and EN techniques in the treatment of nonunion following intramedullary nailing of lower extremity long bones. The search was conducted up until May 2023. The original studies underwent an independent assessment of their quality, a process conducted utilizing the Newcastle-Ottawa scale. Data were retrieved from these studies, and meta-analysis was executed utilizing Review Manager 5.3. RESULTS: This meta-analysis included 8 studies involving 661 participants, with 305 in the AP group and 356 in the EN group. The results of the meta-analysis demonstrated that the AP group exhibited a higher rate of union (odds ratio: 8.61, 95% confidence intervals (CI): 4.12 - 17.99, p < 0.001), shorter union time (standardized mean difference (SMD): -1.08, 95 % CI: -1.79 - -0.37, p = 0.003), reduced duration of the surgical procedure (SMD: -0.56, 95 % CI: -0.93 - -0.19, p = 0.003), less bleeding (SMD: -1.5, 95 % CI: -2.81 - -0.18), p = 0.03), and a lower incidence of complications (relative risk: -0.17, 95 % CI: -0.27 - -0.06, p = 0.001). In the subgroup analysis, the time for union in the AP group in nonisthmal and isthmal nonunion of lower extremity long bones was shorter compared to the EN group (nonisthmal SMD: -1.94, 95 % CI: -3.28 - -0.61, p < 0.001; isthmal SMD: -1.08, 95 % CI: -1.64 - -0.52, p = 0.002). CONCLUSION: In the treatment of nonunion in diaphyseal fractures of the long bones in the lower extremity, the AP approach is superior to EN, both intraoperatively (with reduced duration of the surgical procedure and diminished blood loss) and postoperatively (with an elevated union rate, shorter union time, and lower incidence of complications). Specifically, in the management of nonunion of lower extremity long bones with non-isthmal and isthmal intramedullary nails, AP demonstrated shorter union time in comparison to EN.

[Relationship Between the Expression of Human Matricellular Protein 3 and the Pathological Features, Drug Resistance, and Prognosis of Gastric Cancer Based on Immunohistochemical Method]. / 人母系蛋白3å‚ä¸Žèƒƒç™Œç»†èƒžæ¶æ€§è¡Œä¸ºä¸”ä¸Žæ‚£è€ ä¸è‰¯é¢„åŽç›¸å ³.

Objective: To observe the relationship between the expression of human matricellular protein 3 (MATN3) and the pathological features, drug resistance, and prognosis of gastric cancer based on immunohistochemical method. Methods: A total of 100 gastric cancer patients treated at the First Affiliated Hospital of Bengbu Medical College from January 2022 to December 2022 were included. MATN3 expression in gastric cancer tissues and paracancerous tissues was assessed by immunohistochemistry. The expression of MATN3 was compared across pathological features. Patients were divided into sensitive and resistant groups based on chemotherapy resistance, and MATN3 expression was compared between these groups. The relationship between MATN3 and recurrence-free survival (RFS) and overall survival (OS) of gastric cancer patients was analyzed using Kaplan-Meier survival curves. Univariate and multifactorial Cox regression analyses were used to analyze the factors affecting the prognosis of gastric cancer patients. Human gastric cancer cells MGC803 were transfected with MATN3. The cells were divided into a high expression group (LV-MATN3 group) and its control group (LV-NC group) and a low expression group (sh-MATN3 group) and its control group (sh-NC group). Cell proliferation was assessed using the CCK8 assay, cell migration and invasion were assessed using the Transwell assay, and MATN3 mRNA expression levels were measured using RT-qPCR. A nude mouse xenograft model was constructed by hypodermic injection of MGC-803 cells transfected with MATN3, and MATN3 mRNA expression levels in tumor tissues were measured using RT-qPCR. Results: Immunohistochemical results showed a significantly higher rate of high MATN3 expression in gastric cancer tissues (64.00%, 64/100) compared to adjacent non-cancerous tissues (31.00%, 31/100) (P<0.05). High MATN3 expression was associated with age ≥60 years old, tumor location in the gastric body, tumor size ≥5 cm, lymph node metastasis (N1-N3), histological differentiation (moderate to high), tumor invasion depth (T3-T4), TNM stage (Ⅲ-Ⅳ), distant organ metastasis, recurrence, and mortality (P<0.05). Among patients with chemotherapy resistance, the high MATN3 expression rate was 79.49% (31/39) in the resistant group compared to 54.10% (33/61) in the sensitive group (P<0.05). Follow-up duration ranged from 11 to 22 months, with a 97.00% follow-up rate and 3 cases lost to follow-up. Kaplan-Meier survival curve analysis showed that patients with high MATN3 expression had significantly lower RFS and OS compared to those with low MATN3 expression (RFS: log-rank=17.291, P<0.001; OS: log-rank=21.719, P<0.001). Multivariate Cox analysis identified high MATN3 expression (hazard ratio [HR]=2.291, 95% confidence interval [CI]: 1.268-5.392), tumor location in the gastric body (HR=2.057, 95% CI: 1.441-5.666), lymph node metastasis (N1-N3) (HR=2.011, 95% CI: 1.010-2.274), tumor invasion depth (T3-T4) (H=2.977, 95% CI: 1.032-7.853), TNM stage Ⅲ-Ⅳ (HR=2.008, 95% CI: 1.049-3.902), and distant organ metastasis (HR=2.505, 95% CI: 1.529-5.000) as independent risk factors affecting RFS and OS (P<0.05). Cell and animal experiments demonstrated that compared to the LV-NC group, the LV-MATN3 group exhibited significantly higher cell proliferation, migration, and invasion (P<0.05), as well as increased tumor volume and MATN3 mRNA expression in tumor tissues (P<0.05). Conversely, the sh-MATN3 group showed significantly reduced cell proliferation, migration, and invasion, along with decreased tumor volume and MATN3 mRNA levels compared to the sh-NC group (P<0.05). Conclusion: MATN3 is highly expressed in gastric cancer tissues and is associated with various pathological features, drug resistance and poor prognosis. MATN3 holds potential as a diagnostic marker for poor prognosis and may play a role in the malignant behaviors of gastric cancer cells, including proliferation, migration, and invasion.

[Effect of Hei Xiaoyaosan regulating p38MAPK/Beclin-1/Bcl-2 pathway on autophagy level in Alzheimer's disease model rats].

To explore the effect of Hei Xiaoyaosan on autophagy levels in Alzheimer's disease(AD). A total of 100 4-month-old Wistar male rats were randomly selected as a blank group, and 10 rats were taken as a sham operation group and injected with 1 µL of normal saline on both sides of the hippocampus. The other rats were injected with Aß_(1-42) solution in the hippocampus to replicate the AD model. Fifty successfully modeled rats were selected and randomly divided into the model group, Aricatio group(0.5 mg·kg~(-1)), and high, medium, and low dose groups of Hei Xiaoyaosan(15.30, 7.65, and 3.82 g·kg~(-1)), with 10 rats in each group. The rats were administered by continuous gavage for 42 days. Morris water maze was used to detect the learning and memory ability of rats, and Hoechst staining was used to observe the pathological changes of nerve cells in the hippocampal CA1 region. The mRNA expression of p38MAPK, Beclin-1, and Bcl-2 was detected by RT-qPCR.Western blot was used to detect the expressions of p38MAPK, Beclin-1, Bcl-2, APP, and related proteins. The level of Aß_(1-42) in the hippocampus was detected by ELISA, and the expression level of LC3Ⅱ in the hippocampus was detected by immunohistochemistry. The experimental results showed that compared with the blank group, the learning and memory ability of rats in the model group decreased(P<0.01). The nuclei in the CA1 region of the hippocampus showed blue bright spots and were closely arranged. The mRNA expression of p38MAPK was up-regulated, and the mRNA expressions of Beclin-1 and Bcl-2 were down-regulated(P<0.01). The expressions of p38MAPK, p-p38MAPK, and APP were increased, while those of Beclin-1, Bcl-2, and p-Bcl-2 were decreased(P<0.01). The expression of Aß_(1-42) was increased(P<0.01). The relative expression of LC3Ⅱ decreased(P<0.01). Compared with the model group, the learning and memory ability of rats in each administration group was improved(P<0.05 or P<0.01). The nuclei in the CA1 region of the hippocampus gradually became clear, showing light blue. The mRNA expression of p38MAPK was down-regulated(P<0.01), and that of Beclin-1 and Bcl-2 was increased(P<0.05 or P<0.01). The expressions of p38MAPK, p-p38MAPK, and APP were down-regulated, while those of Beclin-1, Bcl-2, and p-Bcl-2 were up-regulated(P<0.05 or P<0.01). The expression of Aß_(1-42) was decreased(P<0.01). The relative expression of LC3Ⅱ was increased(P<0.01). It can be concluded that Hei Xiaoyaosan can improve the cognitive ability of AD model rats, and its potential mechanism may be related to regulating the p38MAPK/Beclin-1/Bcl-2 signaling pathway, increasing the level of autophagy, and reducing the accumulation of Aß_(1-42).

Effects of SNP marker density and training population size on prediction accuracy in alfalfa (Medicago sativa L.) genomic selection.

Effects of individual single-nucleotide polymorphism (SNP) markers and the size of "training" and "test" populations affect prediction accuracy in genomic selection (GS). This study evaluated 11 subsets of 4932 SNPs using six genetic additive methods to understand marker density in GS prediction in alfalfa (Medicago sativa L.). In the GS methods, the effect of "training" to "test" population size was also evaluated. Fourteen alfalfa populations sampled from long-term grazing sites were genotyped using genotyping by sequencing for the identification of SNPs. These populations were also phenotyped for six agromorphological and three nutritive traits from 2018 to 2020. The accuracy of GS prediction improved across six GS methods when the ratio of "training" to "test" population size increased. However, the prediction accuracy of the six GS methods reduced to a range of -0.27 to 0.11 when random, uninformative SNPs were used. In this study, five Bayesian methods and ridge-regression best linear unbiased prediction (rrBLUP) method had similar GS accuracies for "training" sets, but rrBLUP tended to outperform Bayesian methods in independent "test" sets when SNP subsets with high mean-squared-estimated-marker effect were used. These findings can enhance the application of GS in alfalfa genetic improvement.

Emerging Landscape of Supercharged Proteins and Peptides for Drug Delivery.

Although groundbreaking biotechnological techniques such as gene editing have significantly progressed, the effective and targeted transport of therapeutic agents into host cells remains a major obstacle to the development of biotherapeutics. Confronting the unique challenge posed by large macromolecules such as proteins, peptides, and nucleic acids adds complexity to this issue. Recent findings reveal that the supercharging of proteins and peptides not only enables control over critical properties, such as temperature resistance and catalytic activity, but also holds promise as a viable strategy for their use in drug delivery. This review provides a concise summary of the attributes of supercharged proteins and peptides, encompassing both their natural occurrence and engineered variants. Furthermore, it sheds light on the present status and future possibilities of supercharged proteins and peptides as carriers for significant biomolecules in the realms of medical research and therapeutic applications.