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Background: Well-designed clinical trials are of great importance in validating novel treatments and ensuring an evidence-based approach for sarcoma. This study aimed to provide a comprehensive landscape of the characteristics of metastatic or advanced sarcoma clinical trials using the substantial resource of the ClincialTrials.gov database.Methods: We identified 260,755 trials registered with ClinicalTrials.gov in the last 20 years, and 277 of them were eligible for inclusion. The baseline characteristics were ascertained for each trial. The trials were systematically reviewed to validate their classification into 96 trials registered before 2008 and 181 trials registered between 2008 and 2017.Results: We found that in the last decade, metastatic and advanced sarcoma trials were predominantly phase II-III studies (p = 0.048), were more likely to be ≥2 arms (17.7% vs 35.3%, respectively; p = 0.007), and were more likely to use randomized (13.5% vs 30.4%; p = 0.002) and double-blinded (2.1% vs 9.4%; p = 0.024) assignment than trials registered before 2008. Furthermore, in the last 10-year period, metastatic sarcoma trials were more likely to be conducted in Asia. Treatment involving target therapy and immunotherapy were more common (71.8% vs 37.5%; p < 0.001) than in previous years.Conclusions: Our data showed provocative changes in the sarcoma landscape and demonstrated that the incidence of clinical trials with target therapy and immunotherapy is increasing. These findings emphasize the desperate need for novel strategies, including target therapy and immunotherapy, to improve the outcomes for patients with advanced sarcoma. [ABSTRACT FROM AUTHOR]

Background: Recent mitochondrial phylogenomics studies have reported a sister-group relationship of the orders Capsalidea and Dactylogyridea, which is inconsistent with previous morphology- and molecular-based phylogenies. As Dactylogyridea mitochondrial genomes (mitogenomes) are currently represented by only one family, to improve the phylogenetic resolution, we sequenced and characterized two dactylogyridean parasites, Lamellodiscus spari and Lepidotrema longipenis, belonging to a non-represented family Diplectanidae. Results: The L. longipenis mitogenome (15,433 bp) contains the standard 36 flatworm mitochondrial genes (atp8 is absent), whereas we failed to detect trnS1, trnC and trnG in L. spari (14,614 bp). Both mitogenomes exhibit unique gene orders (among the Monogenea), with a number of tRNA rearrangements. Both long non-coding regions contain a number of different (partially overlapping) repeat sequences. Intriguingly, these include putative tRNA pseudogenes in a tandem array (17 trnV pseudogenes in L. longipenis, 13 trnY pseudogenes in L. spari). Combined nucleotide diversity, non-synonymous/synonymous substitutions ratio and average sequence identity analyses consistently showed that nad2, nad5 and nad4 were the most variable PCGs, whereas cox1, cox2 and cytb were the most conserved. Phylogenomic analysis showed that the newly sequenced species of the family Diplectanidae formed a sister-group with the Dactylogyridae + Capsalidae clade. Thus Dactylogyridea (represented by the Diplectanidae and Dactylogyridae) was rendered paraphyletic (with high statistical support) by the nested Capsalidea (represented by the Capsalidae) clade. Conclusions: Our results show that nad2, nad5 and nad4 (fast-evolving) would be better candidates than cox1 (slow-evolving) for species identification and population genetics studies in the Diplectanidae. The unique gene order pattern further suggests discontinuous evolution of mitogenomic gene order arrangement in the Class Monogenea. This first report of paraphyly of the Dactylogyridea highlights the need to generate more molecular data for monogenean parasites, in order to be able to clarify their relationships using large datasets, as single-gene markers appear to provide a phylogenetic resolution which is too low for the task. [ABSTRACT FROM AUTHOR]

Background: Paratetraonchoides inermis (Monogenea: Tetraonchoididae) is a flatworm parasitising the gills of uranoscopid fishes. Its morphological characteristics are ambiguous, and molecular data have never been used to study its phylogenetic relationships, which makes its taxonomic classification controversial. Also, several decades of unsuccessful attempts to resolve the relationships within the Monogenea present a strong indication that morphological datasets may not be robust enough to be used to infer evolutionary histories. As the use of molecular data is currently severely limited by their scarcity, we have sequenced and characterized the complete mitochondrial (mt) genome of P. inermis. To investigate its phylogenetic position, we performed phylogenetic analyses using Bayesian inference and maximum likelihood approaches using concatenated amino acid sequences of all 12 protein-coding genes on a dataset containing all available monogenean mt genomes. Results: The circular mt genome of P. inermis (14,654 bp) contains the standard 36 genes: 22 tRNAs, two rRNAs, 12 protein-encoding genes (PCGs; Atp8 is missing) and a major non-coding region (mNCR). All genes are transcribed from the same strand. The A + T content of the whole genome (82.6%), as well as its elements, is the highest reported among the monogeneans thus far. Three tRNA-like cloverleaf structures were found in mNCR. Several results of the phylogenomic analysis are in disagreement with previously proposed relationships: instead of being closely related to the Gyrodactylidea, Tetraonchidea exhibit a phylogenetic affinity with the Dactylogyridea + Capsalidea clade; and the order Capsalidea is neither basal within the subclass Monopisthocotylea, nor groups with the Gyrodactylidea, but instead forms a sister clade with the Dactylogyridea. The mt genome of P. inermis exhibits a unique gene order, with an extensive reorganization of tRNAs. Monogenea exhibit exceptional gene order plasticity within the Neodermata. Conclusions: This study shows that gene order within monopisthocotylid mt genomes is evolving at uneven rates, which creates misleading evolutionary signals. Furthermore, our results indicate that all previous attempts to resolve the evolutionary history of the Monogenea may have produced at least partially erroneous relationships. This further corroborates the necessity to generate more molecular data for this group of parasitic animals. [ABSTRACT FROM AUTHOR]

Background: External segmentation and internal proglottization are important evolutionary characters of the Eucestoda. The monozoic caryophyllideans are considered the earliest diverging eucestodes based on partial mitochondrial genes and nuclear rDNA sequences, yet, there are currently no complete mitogenomes available. We have therefore sequenced the complete mitogenomes of three caryophyllideans, as well as the polyzoic Schyzocotyle acheilognathi, explored the phylogenetic relationships of eucestodes and compared the gene arrangements between unsegmented and segmented cestodes. Results: The circular mitogenome of Atractolytocestus huronensis was 15,130 bp, the longest sequence of all the available cestodes, 14,620 bp for Khawia sinensis, 14,011 bp for Breviscolex orientalis and 14,046 bp for Schyzocotyle acheilognathi. The A-T content of the three caryophyllideans was found to be lower than any other published mitogenome. Highly repetitive regions were detected among the non-coding regions (NCRs) of the four cestode species. The evolutionary relationship determined between the five orders (Caryophyllidea, Diphyllobothriidea, Bothriocephalidea, Proteocephalidea and Cyclophyllidea) is consistent with that expected from morphology and the large fragments of mtDNA when reconstructed using all 36 genes. Examination of the 54 mitogenomes from these five orders, revealed a unique arrangement for each order except for the Cyclophyllidea which had two types that were identical to that of the Diphyllobothriidea and the Proteocephalidea. When comparing gene order between the unsegmented and segmented cestodes, the segmented cestodes were found to have the lower similarities due to a long distance transposition event. All rearrangement events between the four arrangement categories took place at the junction of rrnS-tRNAArg (P1) where NCRs are common. Conclusions: Highly repetitive regions are detected among NCRs of the four cestode species. A long distance transposition event is inferred between the unsegmented and segmented cestodes. Gene arrangements of Taeniidae and the rest of the families in the Cyclophyllidea are found be identical to those of the sister order Proteocephalidea and the relatively basal order Diphyllobothriidea, respectively. [ABSTRACT FROM AUTHOR]

Background: Habitat fragmentation may result in the reduction of diversity of parasite communities by affecting population size and dispersal pattern of species. In the flood plain of the Yangtze River in China, many lakes, which were once connected with the river, have become isolated since the 1950s from the river by the construction of dams and sluices, with many larger lakes subdivided into smaller ones by road embankments. These artificial barriers have inevitably obstructed the migration of fish between the river and lakes and also among lakes. In this study, the gastrointestinal helminth communities were investigated in a carnivorous fish, the yellowhead catfish Pelteobagrus fulvidraco, from two connected and five isolated lakes in the flood plain in order to detect the effect of lake fragmentation on the parasite communities. Results: A total of 11 species of helminths were recorded in the stomach and intestine of P. fulvidraco from seven lakes, including two lakes connected with the Yangtze River, i.e. Poyang and Dongting lakes, and five isolated lakes, i.e. Honghu, Liangzi, Tangxun, Niushan and Baoan lakes. Mean helminth individuals and diversity of helminth communities in Honghu and Dongting lakes was lower than in the other five lakes. The nematode Procamallanus fulvidraconis was the dominant species of communities in all the seven lakes. No significant difference in the Shannon-Wiener index was detected between connected lakes (0.48) and isolated lakes (0.50). The similarity of helminth communities between Niushan and Baoan lakes was the highest (0.6708), and the lowest was between Tangxun and Dongting lakes (0.1807). The similarity was low between Dongting and the other lakes, and the similarity decreased with the geographic distance among these lakes. The helminth community in one connected lake, Poyang Lake was clustered with isolated lakes, but the community in Dongting Lake was separated in the tree. Conclusion: The similarity in the helminth communities of this fish in the flood-plain lakes may be attributed to the historical connection of these habitats and to the completion of the life-cycles of this fish as well as the helminth species within the investigated habitats. The diversity and the digenean majority in the helminth communities can be related to the diet of this fish, and to the lacustrine and macrophytic characters of the habitats. The lake isolation from the river had little detectable effect on the helminth communities of the catfish in flood-plain lakes of the Yangtze River. The low similarities in helminth communities between the Dongting Lake and others may just be a reflection of its unique water environment and anthropogenic alterations or fragmentation in this lake. [ABSTRACT FROM AUTHOR]

Background: In this study, we have investigated the viscoelastic behaviour of individual human adult bone marrow-derived mesenchymal stem cells (hMSCs) and the role of F-actin filaments in maintaining these properties, using micropipette aspiration technique together with a standard linear viscoelastic solid model. Results: Under a room temperature of 20°C, the instantaneous and equilibrium Young's modulus, E0 and E∞, were found to be 886 ± 289 Pa and 372 ± 125 Pa, respectively, while the apparent viscosity, μ, was 2710 ± 1630 Pa·s. hMSCs treated with cytochalasin D up to 20 µM at 20°C registered significant drop of up to 84% in stiffness and increase of up to 255% in viscosity. At the physiological temperature of 37°C, E0 and E∞ have decreased by 4266% whereas μ has increased by 95%, compared to the control. Majority of the hMSCs behave as viscoelastic solid with a rapid initial increase in aspiration length and it gradually levels out with time. Three other types of non-typical viscoelastic behavior of hMSCs were also seen. Conclusion: hMSCs behave as viscoelastic solid. Its viscoelstic behaviour are dependent on the structural integrity of the F-actin filaments and temperature. [ABSTRACT FROM AUTHOR]

Background: Numerous studies have indicated a growing prevalence of hyperuricemia. Elevated levels of serum uric acid (SUA) have been established as influential factors in conditions such as obesity, metabolic syndrome, diabetes mellitus, gout, and cardiovascular disease. Overweight and obesity are closely related to an increase in SUA. Our objective is to demonstrate the mediating role of liver enzyme in the correlation between body mass index (BMI) and SUA., Methods: A total of 5925 adults aged 18 to 65 were included in this cross-sectional study. Logistic regression and mediation analysis were used to investigate the relationship between BMI and hyperuricemia as well as liver enzyme levels. Standard methods were used to determine the biochemical indexes, including SUA, liver enzymes, and blood lipids in the collected samples., Results: The study revealed that the prevalence of hyperuricemia was 28.0%. Furthermore, the prevalence of overweight and obesity was as high as 48.5%, with 70.7% of this subgroup presenting with hyperuricemia. There was a positive correlation between BMI and hyperuricemia, and elevated levels of liver enzymes (ALT, AST, GGT) were associated with a higher risk of hyperuricemia. The study also observed a positive correlation between BMI and liver enzymes (ALT, AST, GGT). The study findings suggested that ALT, AST, and GGT played significant mediating roles in the relationship between BMI and SUA. Specifically, the unadjusted model revealed that ALT and GGT accounted for 22.12% and 18.13% of the mediation effects, respectively., Conclusions: The study found that BMI is associated with hyperuricemia, where liver enzyme abnormalities may have a mediating role. It is suggested that being overweight or obese may affect liver enzyme levels, leading to increased SUA levels. Controlling weight and liver enzyme levels may help prevent and treat hyperuricemia., (© 2024. The Author(s).)

Natural compound-based treatments provide innovative ways for ulcerative colitis therapy. However, poor targeting and rapid degradation curtail its application, which needs to be addressed. Inspired by biomacromolecule-based materials, we have developed an orally administrated nanoparticle (GBP@HA NPs) using bovine serum albumin as a carrier for polyphenol delivery. The system synergizes galactosylated bovine serum albumin with two polyphenols, epigallocatechin gallate and tannic acid, which is then encased in "nanoarmor" of ε-Polylysine and hyaluronic acid to boost its stability and targeting. Remarkably, the nanoarmor demonstrated profound therapeutic effects in both acute and chronic mouse models of ulcerative colitis, mitigating disease symptoms via multiple mechanisms, regulating inflammation related factors and exerting a modulatory impact on gut microbiota. Further mechanistic investigations indicate that GBP@HA NPs may act through several pathways, including modulation of Keap1-Nrf2 and NF-κB signaling, as well as Caspase-1-dependent pyroptosis. Consequently, this novel armored nanotherapy promotes the way for enhanced polyphenol utilization in ulcerative colitis treatment research., (© 2024. The Author(s).)

Background: Although there is considerable evidence of a robust correlation between rheumatoid arthritis (RA) and carpal tunnel syndrome (CTS) in previous research, the causal link between the two remains a topic of controversy., Methods: We conducted a two-sample Mendelian randomization (MR) study to explore the causal impact of RA on CTS. We obtained aggregate data from genome-wide association studies (GWAS) of CTS (ebi database and GEO database) and RA (FinnGen database). This study employed five MR analysis methods, with a focus on the inverse variance-weighted (IVW) method. Sensitivity analyses were conducted to ensure the robustness of the results of this study. Additionally, we performed reverse MR analysis., Results: We selected 84 and 78 single nucleotide polymorphisms (SNPs) significantly associated with RA from two databases as instrumental variables (IVs), respectively. Our results showed that RA patients have a higher risk of getting CTS regardless of whether the ebi database (IVW, OR = 1.045, 95% CI: 1.016-1.075, P = 0.002) or the GEO database (IVW, OR = 1.001, 95% CI: 1.001-1.002, P = 0.001) is selected for CTS data. However, the MR analysis showed no causal link between CTS and the increased risk of RA (ebi: IVW, OR = 1.084, 95% CI: 0.918-1.279, P = 0.341; GEO: IVW, OR = 1.968, 95% CI: 0.011-360.791, P = 0.799)., Conclusion: The analysis revealed that RA can increase the risk of CTS, but did not support the causal relationship that CTS can increase the risk of RA., (© 2024. The Author(s).)

Background: The cGAS-STING pathway is an important component of the innate immune system and plays significant role in acetaminophen-induced liver injury (AILI). Pentagalloylglucose (PGG) is a natural polyphenolic compound with various beneficial effects, including anti-cancer, antioxidant, anti-inflammatory, and liver-protective properties; however, whether it can be used for the treatment of AILI and the specific mechanism remain unclear., Materials and Methods: A cell culture model was created to study the effect of PGG on cGAS-STING pathway activation using various techniques including western blotting (WB), real-time quantitative polymerase chain reaction (RT-qPCR), immunofluorescence (IF), and immunoprecipitation (IP). The effect of PGG was investigated in vivo by establishing a dimethylxanthenone acetic acid (DMXAA)-mediated activation model. An AILI model was used to evaluate the hepatoprotective and therapeutic effects of PGG by detecting liver function indicators, liver histopathology, and cGAS-STING pathway-related indicators in mice with AILI., Results: PGG blocked cGAS-STING pathway activation in bone marrow-derived macrophages (BMDMs), THP-1 cells, and peripheral blood mononuclear cells (PBMCs) in vitro. Furthermore, PGG inhibited the generation of type I interferons (IFN-I) and the secretion of inflammatory factors in DMXAA-induced in vivo experiments. In addition, PGG also reduced serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP), improved liver tissue damage and apoptosis, and inhibited the cGAS-STING pathway activation caused by acetaminophen. In terms of the mechanism, PGG disrupted the connection between STING and TBK1., Conclusions: PGG exerts a protective effect against AILI by blocking the cGAS-STING pathway, offering a promising treatment strategy., (© 2024. The Author(s).)

Glioblastoma (GBM), the most common primary brain malignancy in adults, is notoriously difficult to treat due to several factors: tendency to be radiation resistant, the presence of the blood brain barrier (BBB) which limits drug delivery and immune-privileged status which hampers effective immune responses. Traditionally, high-dose irradiation (8 Gy) is known to effectively enhance anti-tumor immune responses, but its application is limited by the risk of severe brain damage. Currently, conventional dose segmentation (2 Gy) is the standard radiotherapy method, which does not fully exploit the potential of high-dose irradiation for immune activation. The hypothesis of our study posits that instead of directly applying high doses of radiation, which is risky, a strategy could be developed to harness the immune-stimulating benefits of high-dose irradiation indirectly. This involves using nanoparticles to enhance antigen presentation and immune responses in a safer manner. Angiopep-2 (A2) was proved a satisfactory BBB and brain targeting and Dbait is a small molecule that hijack DNA double strand break damage (DSB) repair proteins to make cancer cells more sensitive to radiation. In view of that, the following two nanoparticles were designed to combine immunity of GBM, radiation resistance and BBB innovatively. One is cationic liposome nanoparticle interacting with Dbait (A2-CL/Dbait NPs) for radiosensitization effect; the other is PLGA-PEG-Mal nanoparticle conjugated with OX40 antibody (A2-PLGA-PEG-Mal/anti-OX40 NPs) for tumor-derived protein antigens capture and optimistic immunoregulatory effect of anti-OX40 (which is known to enhance the activation and proliferation T cells). Both types of nanoparticles showed favorable targeting and low toxicity in experimental models. Specifically, the combination of A2-CL/Dbait NPs and A2-PLGA-PEG-Mal/anti-OX40 NPs led to a significant extension in the survival time and a significant tumor shrinkage of mice with GBM. The study demonstrates that combining these innovative nanoparticles with conventional radiotherapy can effectively address key challenges in GBM treatment. It represents a significant step toward more effective and safer therapeutic options for GBM patients., (© 2024. The Author(s).)

Background: The escalating global prevalence of polypharmacy presents a growing challenge to public health. In light of this issue, the primary objective of our study was to investigate the status of polypharmacy and its association with clinical outcomes in a large sample of hospitalized older patients aged 65 years and over., Methods: A two-year prospective cohort study was carried out at six tertiary-level hospitals in China. Polypharmacy was defined as the prescription of 5 or more different medications daily, including over-the-counter and non-prescription medications. Baseline polypharmacy, multimorbidity, and other variables were collected when at admission, and 2-year outcomes were recorded by telephone follow-up. We used multivariate logistic regression analysis to examine the associations between polypharmacy and 2-year outcomes., Results: The overall response rate was 87.2% and 8713 participants were included in the final analysis. The mean age was 72.40 years (SD = 5.72), and women accounted for 42.2%. The prevalence of polypharmacy among older Chinese inpatients is 23.6%. After adjusting for age, sex, education, marriage status, body mass index, baseline frailty, handgrip strength, cognitive impairment, and the Charlson comorbidity index, polypharmacy is significantly associated with frailty aggravation (OR 1.432, 95% CI 1.258-1.631) and mortality (OR 1.365, 95% CI 1.174-1.592), while inversely associated with readmission (OR 0.870, 95% CI 0.764-0.989). Polypharmacy was associated with a 35.6% increase in the risk of falls (1.356, 95%CI 1.064-1.716). This association weakened after adjustment for multimorbidity to 27.3% (OR 1.273, 95%CI 0.992-1.622)., Conclusions: Polypharmacy was prevalent among older inpatients and was a risk factor for 2-year frailty aggravation and mortality. These results highlight the importance of optimizing medication use in older adults to minimize the risks associated with polypharmacy. Further research and implementing strategies are warranted to enhance the quality of care and safety for older individuals exposed to polypharmacy., Trial Registration: Chinese Clinical Trial Registry, ChiCTR1800017682, registered 09/08/2018., (© 2024. The Author(s).)

Background: Catheter-associated urinary tract infection (CAUTI) remains the most significant challenge among hospital-acquired infections (HAIs), yet still unresolved. The present study aims to evaluate the preventive effectiveness of JUC Spray Dressing (name of U.S. FDA and CE certifications, while the medical device name in China is Long-acting Antimicrobial Material) alone for CAUTI without combining with antibiotics and to evaluate the impact of bacterial biofilm formation on CAUTI results on the inserted catheters of patients., Methods: In this multicenter, randomized, double-blind study, we enrolled adults who suffered from acute urinary retention (AUR) and required catheterization in 6 hospitals in China. Participants were randomly allocated 1:1 according to a random number table to receive JUC Spray Dressing (JUC group) or normal saline (placebo group). The catheters were pretreated with JUC Spray Dressing or normal saline respectively before catheterization. Urine samples and catheter samples were collected after catheterization by trial staff for further investigation., Results: From April 2012 to April 2020, we enrolled 264 patients and randomly assigned them to the JUC group (n = 132) and the placebo group (n = 132). Clinical symptoms and urine bacterial cultures showed the incidence of CAUTI of the JUC group was significantly lower than the placebo group (P < 0.01). In addition, another 30 patients were enrolled to evaluate the biofilm formation on catheters after catheter insertion in the patients' urethra (10 groups, 3 each). The results of scanning electron microscopy (SEM) showed that bacterial biofilm formed on the 5th day in the placebo group, while no bacterial biofilm formed on the 5th day in the JUC group. In addition, no adverse reactions were reported using JUC Spray Dressing., Conclusion: Continued indwelling urinary catheters for 5 days resulted in bacterial biofilm formation, and pretreatment of urethral catheters with JUC Spray Dressing can prevent bacterial biofilm formation by forming a physical antimicrobial film, and significantly reduce the incidence of CAUTI. This is the first report of a study on inhibiting bacterial biofilm formation on the catheters in CAUTI patients., (© 2024. The Author(s).)

Background: Using event-related potentials (ERPs), we aimed to investigate audiovisual integration neural mechanisms during a letter identification task in the left and right sides. Unimodal (A,V) and bimodal (AV) stimuli were presented on either side, with ERPs from unimodal (A,V) stimuli on the same side being compared to those from simultaneous bimodal stimuli (AV). Non-zero results of the AV-(A + V) difference waveforms indicated audiovisual integration on the left/right side., Results: When spatially coherent AV stimuli were presented on the right side, two significant ERP components in the integrated differential wave were noted. The N134 and N262, present in the first 300 ms of the AV-(A + V) integration difference wave, indicated significant audiovisual integration effects. However, when these stimuli were presented on the left side, there were no significant integration components. This audiovisual integration difference may stem from left/right asymmetry of cerebral hemisphere language processing., Conclusions: Audiovisual letter information presented on the right side was easier to integrate, process, and represent. Additionally, only one significant integrative component peaked at 140 ms in the parietal cortex for spatially non-coherent AV stimuli and provided audiovisual multisensory integration, which could be attributed to some integrative neural processes that depend on the spatial congruity of the auditory and visual stimuli., (© 2024. The Author(s).)

Objective: To investigate the association between a low oocyte maturity ratio from in vitro fertilization cycle and blastocyst euploidy., Methods: A total of 563 preimplantation genetic testing (PGT) cycles (PGT cycles with chromosomal structural rearrangements were excluded) were performed between January 2021 and November 2022 at our center (average oocyte maturity rate: 86.4% ± 14.6%). Among them, 93 PGT cycles were classified into the low oocyte maturity rate group (group A, < mean - 1 standard deviation [SD]), and 186 PGT cycles were grouped into the average oocyte maturity rate group (group B, mean ± 1 SD). Group B was 2:1 matched with group A. Embryological, blastocyst ploidy, and clinical outcomes were compared between the two groups., Results: The oocyte maturity (metaphase II [MII oocytes]), MII oocyte rate, and two pronuclei (2PN) rates were significantly lower in group A than in group B (5.2 ± 3.0 vs. 8.9 ± 5.0, P = 0.000; 61.6% vs. 93.0%, P = 0.000; 78.7% vs. 84.8%, P = 0.002, respectively). In group A, 106 of 236 blastocysts (44.9%) that underwent PGT for aneuploidy were euploid, which was not significantly different from the rate in group B (336/729, 46.1%, P = 0.753). However, euploid blastocysts were obtained only in 55 cycles in group A (55/93, 59.1%), which was lower than the rate in group B (145/186, 78.0%, P = 0.001). The clinical pregnancy rate in group B (73.9%) was higher than that in group A (58.0%) (P = 0.040)., Conclusion: Our results suggest that a low oocyte maturity ratio is not associated with blastocyst euploidy but is associated with fewer cycles with euploid blastocysts for transfer, lower 2PN rates, and lower clinical pregnancy rates., (© 2024. The Author(s).)

Background: An important signaling pathway connecting illness and natural immunity is the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, but aberrant activation of this pathway is associated with the development of autoimmune and inflammatory diseases. Hence, targeted inhibition of the activation of the cGAS-STING pathway is potentially valuable in the treatment of disease. The primary active component of Salvia miltiorrhiza is total tanshinone (TTN). Research has indicated that TTN possesses noteworthy anti-inflammatory properties. However, the protective mechanism of TTN against acute liver injury (ALI) and autoimmune diseases is unknown., Methods: A model of aberrant activation of the cGAS-STING pathway was established in various cells and treated with TTN, and the expression of cGAS-STING pathway-related proteins, type I interferon, interferon stimulated genes and inflammatory factors was assessed by western blotting, real-time qPCR. Immunofluorescence analysis of the effect of TTN on the entry of associated proteins into the nucleus following aberrant activation of the cGAS-STING pathway. The effect of TTN on STING oligomerisation was investigated using 2'-3'-cyclic GMP-AMP (2',3'-cGAMP) to induce STING oligomerisation. Western blotting was used to examine the impact of TTN on the interactions of STING, tank-binding kinase 1 (TBK1), and interferon regulatory factor 3 (IRF3) after HA or Flag-labelled plasmids were transfected into HEK-293 T cells. A dimethylxanthenone-4-acetic acid (DMXAA) -induced activation model of the cGAS-STING pathway in mice was established to study the effect of TTN on aberrant activation of the cGAS-STING pathway in vivo. On the other hand, an animal model of lipopolysaccharide/D-galactosamine (LPS/D-GaIN)-induced ALI and an autoimmune disease model induced by trex1 knockout were established to study the effects of TTN on inflammatory and autoimmune diseases mediated by the cGAS-STING pathway in vivo., Results: In several models of aberrant activation of the cGAS-STING pathway, TTN significantly inhibited the phosphorylation of STING and IRF3, thereby suppressing the expression of type I interferon, interferon-stimulated genes and inflammatory factors. Additionally, TTN prevented P65 and IRF3 from entering the nucleus after the cGAS-STING signalling pathway was abnormally activated. Subsequent research indicated that TTN was not involved in the oligomerization of STING or the integration of STING-TBK1 and TBK1-IRF3. However, TTN was found to have a substantial effect on the binding process between STING and IRF3. On the other hand, DMXAA-induced STING activation and activation of downstream signalling in vivo are inhibited by TTN. Furthermore, TTN exhibits positive treatment effects on autoimmune diseases caused by deficiency of trex1 and LPS/D-GaIN-induced ALI., Conclusion: Our research indicates that TTN effectively treats ALI and autoimmune illnesses mediated by the cGAS-STING pathway by inhibiting the abnormal activation of this pathway., (© 2024. The Author(s).)

The Phosphatidylinositol-3-kinase (PI3K) family is well-known to comprise three classes of intracellular enzymes. Class I PI3Ks primarily function in signaling by responding to cell surface receptor stimulation, while class II and III are more involved in membrane transport. Under normal physiological conditions, the PI3K signaling network orchestrates cell growth, division, migration and survival. Aberrant activation of the PI3K signaling pathway disrupts cellular activity and metabolism, often marking the onset of cancer. Currently, the Food and Drug Administration (FDA) has approved the clinical use of five class I PI3K inhibitors. These small-molecule inhibitors, which exhibit varying selectivity for different class I PI3K family members, are primarily used in the treatment of breast cancer and hematologic malignancies. Therefore, the development of novel class I PI3K inhibitors has been a prominent research focus in the field of oncology, aiming to enhance potential therapeutic selectivity and effectiveness. In this review, we summarize the specific structures of PI3Ks and their functional roles in cancer progression. Additionally, we critically evaluate small molecule inhibitors that target class I PI3K, with a particular focus on their clinical applications in cancer treatment. Moreover, we aim to analyze therapeutic approaches for different types of cancers marked by aberrant PI3K activation and to identify potential molecular targets amenable to intervention with small-molecule inhibitors. Ultimately, we propose future directions for the development of therapeutic strategies that optimize cancer treatment outcomes by modulating the PI3K family., (© 2024. The Author(s).)

Background: Radioresistance and immune escape are crucial reasons for unsatisfactory therapeutic effects of glioblastoma (GBM). Although triggering receptor expressed on myeloid cells-2 (TREM2) involved in forming immunosuppressive microenvironment, but the underlying mechanism and its roles in mediating cancer radioresistance remain unclear, moreover, the efficient delivery of drugs targeting TREM2 to GBM encounters serious challenges. Hence, this study aimed to elucidate the effect and mechanisms of targeted TREM2 silencing on reversing the radioresistance and immune escape of GBM aided by a glutathione-responsive biomimetic nanoparticle (NP) platform., Methods: Radioresistant GBM cell lines and TREM2 stable knockdown GBM cell lines were firstly established. RNA sequencing, colony formation assay, western blot, enzyme-linked immunosorbent assay and co-immunoprecipitation assay were used to detect the molecular mechanisms of TREM2 in regulating the radioresistance and immune escape of GBM. The glutathione-responsive biomimetic NP, angiopep-2 (A2)- cell membrane (CM)-NP/siTREM2/spam1, was then constructed to triply and targeted inhibit TREM2 for in vivo study. Orthotopic GBM-bearing mouse models were established to evaluate the anti-GBM effect of TREM2 inhibition, multiplex immunofluorescence assay was conducted to detect the infiltration of immune cells., Results: TREM2 was a regulator in accelerating the radioresistance and immune escape of GBM through participating in DNA damage repair and forming a positive feedback loop with high mobility group box 1 (HMGB1) to cascade the activation of Toll-like receptor 4 (TLR4)/protein kinase B (Akt) signaling. A2-CM-NP/siTREM2/spam1 was successfully synthesized with excellent passive targeting, active targeting and homologous targeting, and the in vivo results exhibited its remarkable anti-GBM therapeutic effect through promoting the infiltration of type 1 helper T cells and CD8 + T cells, reducing the infiltration of type 2 helper T cells and regulatory T cells, repolarizing macrophages to M1-type, and decreasing the secretion of pro-tumor and immunosuppressive cytokines., Conclusions: Targeting TREM2 therapy is a promising avenue for optimizing radiotherapy and immunotherapy to improve the prognosis of GBM patients., (© 2024. The Author(s).)

Objectives: To compare the iatrogenic radial nerve injury (iRNI) rate of different implant (plate vs. intramedullary nail) and surgical approaches during humeral shaft fracture surgery., Methods: The online PubMed database was used to search for articles describing iRNI after humeral fracture with a publication date from Jan 2000 to October 2023. The following types of articles were selected: (1) case series associating with adult humeral shaft fracture, preoperative radial nerve continuity, non-pathological fracture and non-periprosthetic fracture; (2) involving humeral shaft (OTA/AO 12) fractures. Articles where we were unable to judge surgical approach or fracture pattern (OTA/AO 12) were excluded. The data were analyzed by SPSS 27.0 and Chi-square test was performed to identify incidence of iRNI associated with different implant and surgical approaches., Results: Fifty-four articles with 5063 cases were included, with 3510 cases of the plate, 830 cases of intramedullary nail and 723 cases of uncertain internal fixation. The incidences of iRNI with plate and intramedullary nail were 5.95% (209/3510) and 2.77% (23/830) (p < 0.05). And iRNI incidences of different surgical approaches were 3.7% (3/82) for deltopectoral approach, 5.74% (76/1323) for anterolateral approach, 13.54% (26/192) for lateral approach and 6.68% (50/749) for posterior approach. The iRNI rates were 0.00% (0/33) for anteromedial MIPO, 2.67% (10/374) for anterolateral MIPO and 5.40% (2/37) for posterior MIPO (p > 0.05). The iRNI rates were 2.87% (21/732) for anterograde intramedullary nail and 2.04% (2/98) for retrograde intramedullary nail (p > 0.05). In humeral bone nonunion surgery, the rate of iRNI was 15.00% (9/60) for anterolateral approach, 16.7% (2/12) for lateral approach and 18.2% (6/33) for posterior approach (p  > 0.05)., Conclusion: Intramedullary nailing is the preferred method of internal fixation for humeral shaft fractures that has the lowest rate of iRNI. Compared with anterolateral and posterior approaches, the lateral surgical approach had a higher incidence of iRNI. The rate of iRNI in MIPO was lower than that in open reduction and internal fixation., Level of Evidence: Level IV., (© 2024. The Author(s).)

Endometrial cancer (EC) stem cells (ECSCs) are pivotal in the oncogenesis, metastasis, immune escape, chemoresistance, and recurrence of EC. However, the specific mechanism of stem cell maintenance in EC cells (ECCs) has not been clarified. We found that WTAP and m6A levels decreased in both EC and ECSCs, and that knocking down WTAP promoted ECCs and ECSCs properties, including proliferation, invasion, migration, cisplatin resistance, and self-renewal. The downregulation of WTAP leads to a decrease in the m6A modification of EGR1 mRNA, and it is difficult for IGF2BP3, as an m6A reader, to recognize and bind to EGR1 mRNA that has lost m6A modification, resulting in a decrease in the stability of EGR1 mRNA. A decrease in the EGR1 level led to a decrease of in the expression tumor suppressor gene PTEN, resulting in deregulation and loss of cellular homeostasis and thereby fostering EC stem cell traits. Notably, the enforced overexpression of WTAP, EGR1, and PTEN inhibited the oncogenic effects of ECCs and ECSCs in vivo, and the combined overexpression of WTAP + EGR1 and EGR1 + PTEN further diminished the tumorigenic potential of these cells. Our findings revealed that the WTAP/EGR1/PTEN pathway is important regulator of EC stem cell maintenance, chemotherapeutic resistance, and tumorigenesis, suggesting a novel and promising therapeutic avenue for treating EC., (© 2024. The Author(s).)

Mediastinal myelolipoma is a rare condition and has no obvious symptoms. In the past 20 years, some clinical cases have been documented. However, the literature has not systematically summarized its imaging features. The aim of this paper is to present a case of right posterior mediastinal myelolipoma and to review and summarize its imaging features. Twenty-six articles were included in our study, which included a total of 26 patients and 33 lesions; 90.9% of the lesions were located in the mediastinum at the level from the 8th thoracic vertebral body to the thoracic 12th vertebral body. Among the cases with unilateral mediastinum, 68.4% of the cases were located in the right posterior mediastinum. Bilateral lesions accounted for almost one-fourth of all lesions. After contrast medium was injected, 93.9% of the lesions had mild to moderate enhancement; 84.8% of the lesions contained fat density; and 75.8%, 69.7%, 87.9%, and 75.8% of the lesions showed clear boundary, regular shape, heterogeneity and were encapsulated, respectively. Only 12.1% of the lesions contained calcification. An inhomogeneous mass in the right posterior mediastinum near the spine, including fat density, is the predominant imaging marker of most mediastinal myelolipomas., (© 2024. The Author(s).)

Objective: The aim of this study was to explore the effects of vitamin D supplementation on metabolic parameters in women with polycystic ovary syndrome (PCOS)., Methods: A total of 60 PCOS women with vitamin D deficiency or insufficiency were enrolled in this randomized controlled trial. Participants were randomized to vitamin D group (2000 IU/day) or control group. The observational parameters were measured at baseline and after treatment, including body mass index (BMI), waist to hip ratio (WHR), oral glucose tolerance test (OGTT) and insulin release test, and lipid metabolism parameters., Results: The serum 25(OH)D concentrations at different time points after vitamin D supplementation were significantly higher than that in control group (P < 0.05). The BMI, WHR, insulin concentrations, homeostasis model assessment of insulin resistance (HOMA-IR), triglycerides (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) concentrations in women of Vitamin D group after 12 weeks of treatment were significantly lower than that in women of control group (P < 0.05). The serum insulin concentrations and HOMA-IR at different time points of OGTT, serum TG, TC and LDL-C concentrations in women of vitamin D group (obesity) were significantly lower compared with control group (obesity) (P < 0.05). The BMI, WHR, TG, TC and LDL-C concentration in women of vitamin D group (IR) were significantly lower compared with control group (IR) (P < 0.05). No significant difference was observed in metabolic parameters between vitamin D group (non-obesity) and control group (non-obesity) (P > 0.05), and these differences of metabolic parameters were also not observed between vitamin D group (non-IR) and control group (non-IR) (P > 0.05)., Conclusion: Vitamin D supplementation had beneficial effects on metabolic parameters in PCOS women, especially in women with obesity or insulin resistance., (© 2024. The Author(s).)

Previous studies have shown that antimicrobial photodynamic inactivation (aPDI) can be strongly potentiated by the addition of the non-toxic inorganic salt, potassium iodide (KI). This approach was shown to apply to many different photosensitizers, including the xanthene dye Rose Bengal (RB) excited by green light (540 nm). Rose Bengal diacetate (RBDA) is a lipophilic RB derivative that is easily taken up by cells and hydrolyzed to produce an active photosensitizer. Because KI is not taken up by microbial cells, it was of interest to see if aPDI mediated by RBDA could also be potentiated by KI. The addition of 100 mM KI strongly potentiated the killing of Gram-positive methicillin-resistant Staphylocccus aureus, Gram-negative Eschericia coli, and fungal yeast Candida albicans when treated with RBDA (up to 15 µM) for 2 hours followed by green light (540 nm, 10 J/cm 2 ). Both RBDA aPDI regimens (400 µM RBDA with or without 400 mM KI followed by 20 J/cm 2 green light) accelerated the healing of MRSA-infected excisional wounds in diabetic mice, without damaging the host tissue., (© 2024. The Author(s).)

Background: Early screening and detection of lung cancer is essential for the diagnosis and prognosis of the disease. In this paper, we investigated the feasibility of serum Raman spectroscopy for rapid lung cancer screening., Methods: Raman spectra were collected from 45 patients with lung cancer, 45 with benign lung lesions, and 45 healthy volunteers. And then the support vector machine (SVM) algorithm was applied to build a diagnostic model for lung cancer. Furthermore, 15 independent individuals were sampled for external validation, including 5 lung cancer patients, 5 benign lung lesion patients, and 5 healthy controls., Results: The diagnostic sensitivity, specificity, and accuracy were 91.67%, 92.22%, 90.56% (lung cancer vs. healthy control), 92.22%,95.56%,93.33% (benign lung lesion vs. healthy) and 80.00%, 83.33%, 80.83% (lung cancer vs. benign lung lesion), repectively. In the independent validation cohort, our model showed that all the samples were classified correctly., Conclusion: Therefore, this study demonstrates that the serum Raman spectroscopy analysis technique combined with the SVM algorithm has great potential for the noninvasive detection of lung cancer., (© 2024. The Author(s).)

Objective: Segmental bone defect animal studies require stable fixation which is a continuous experimental challenge. Large animal models are comparable to the human bone, but with obvious drawbacks of housing and costs. Our study aims to utilize CAD and 3D printing in the construction of a stable and reproducible segmental bone defect animal mode., Methods: CAD-aided 3D printed surgical instruments were incorporated into the construction of the animal model through preoperative surgical emulation. 20 3D printed femurs were divided into either experimental group using 3D surgical instruments or control group. In Vitro surgical time and accuracy of fixation were analysed and compared between the two groups. A mature surgical plan using the surgical instruments was then utilized in the construction of 3 segmental bone defect Beagle models in vivo. The Beagles were postoperatively assessed through limb function and imaging at 1, 2 and 3 months postoperatively., Results: In vitro experiments showed a significant reduction in surgical time from 40.6 ± 14.1 (23-68 min) to 26 ± 4.6 (19-36 min) (n = 10, p < 0.05) and the accuracy of intramedullary fixation placement increased from 71.6 ± 23.6 (33.3-100) % to 98.3 ± 5.37 (83-100) %, (n = 30, p < 0.05) with the use of CAD and 3D printed instruments. All Beagles were load-bearing within 1 week, and postoperative radiographs showed no evidence of implant failure., Conclusion: Incorporation of CAD and 3D printing significantly increases stability, while reducing the surgical time in the construction of the animal model, significantly affecting the success of the segmental bone defect model in Beagles., (© 2024. The Author(s).)

Background: Psychological empowerment notably impacts nurses' work engagement and high-quality care. A spiritual climate is a work environment that respects individuals and encourages them to express personal views. Previous studies have shown that a spiritual climate enhances psychological empowerment, however, the relationship between them among the nursing population remains unclear. This study aimed to explore the effect of a spiritual climate on nurses' psychological empowerment and provide a scientific basis for improving psychological empowerment among nurses., Methods: A cross-sectional survey of 837 nurses from five hospitals in Sichuan Province, Southwest China, was conducted using a convenience sampling method; this survey included nurses' demographic characteristics, the Psychological Empowerment Scale (PES), and the Chinese version of the Spiritual Climate Scale (C-SCS). The data were analysed using one-way analysis of variance (ANOVA), correlation analysis, and multiple linear regression., Results: The sample of 837 nurses attained a psychological empowerment score of (45.49 ± 6.42) and a spiritual climate score of (75.25 ± 16.75). The one-way ANOVA revealed that psychological empowerment scores among nurses varied based on differences in age, department, years of work experience, professional title, level of work intensity, and children (yes/no). Pearson's correlation analyses revealed a significant positive correlation between the spiritual climate and nurses' psychological empowerment (r = 0.564, P < 0.001), and multiple linear regression analysis showed that working in the intensive care unit (ICU), work intensity, and the four items pertaining to spiritual climate influenced nurses' psychological empowerment, explaining 32.6% of the total variance in psychological empowerment., Conclusion: The findings suggested that the spiritual climate perceived by nurses and psychological empowerment are moderately high. Working in the ICU, work intensity, and the four items pertaining to spiritual climate influence nurses' psychological empowerment. Nursing managers should pay attention to the daily work intensity of nurses, especially ICU nurses, organize work tasks reasonably, promote dynamic and balanced nurse human resource deployment based on patients' conditions and nurses' workloads, and implement scientific scheduling plans to establish a positive spiritual climate in the workplace. Additionally, group workshops and systematic training programs can effectively enhance psychological empowerment among nurses., (© 2024. The Author(s).)

Mitogen-activated protein kinase inhibitors (MAPKi) were the first line drugs for advanced melanoma patients with BRAF mutation. Targeted therapies have significant therapeutic effects; however, drug resistance hinders their long-term efficacy. Therefore, the development of new therapeutic strategies against MAPKi resistance is critical. Our previous results showed that MAPKi promote feedback activation of STAT3 signaling in BRAF-mutated cancer cells. Studies have shown that alantolactone inhibited the activation of STAT3 in a variety of tumor cells. Our results confirmed that alantolactone suppressed cell proliferation and promoted apoptosis by inhibiting STAT3 feedback activation induced by MAPKi and downregulating the expression of downstream Oct4 and Sox2. The inhibitory effect of alantolactone combined with a MAPKi on melanoma cells was significantly stronger than that on normal cells. In vivo and in vitro experiments showed that combination treatment was effective against drug-resistant melanomas. Our research indicates a potential novel combination therapy (alantolactone and MAPKi) for patients with BRAF-mutated melanoma., (© 2024. The Author(s).)

Background: Accurate segmentation of critical anatomical structures in fetal four-chamber view images is essential for the early detection of congenital heart defects. Current prenatal screening methods rely on manual measurements, which are time-consuming and prone to inter-observer variability. This study develops an AI-based model using the state-of-the-art nnU-NetV2 architecture for automatic segmentation and measurement of key anatomical structures in fetal four-chamber view images., Methods: A dataset, consisting of 1,083 high-quality fetal four-chamber view images, was annotated with 15 critical anatomical labels and divided into training/validation (867 images) and test (216 images) sets. An AI-based model using the nnU-NetV2 architecture was trained on the annotated images and evaluated using the mean Dice coefficient (mDice) and mean intersection over union (mIoU) metrics. The model's performance in automatically computing the cardiac axis (CAx) and cardiothoracic ratio (CTR) was compared with measurements from sonographers with varying levels of experience., Results: The AI-based model achieved a mDice coefficient of 87.11% and an mIoU of 77.68% for the segmentation of critical anatomical structures. The model's automated CAx and CTR measurements showed strong agreement with those of experienced sonographers, with respective intraclass correlation coefficients (ICCs) of 0.83 and 0.81. Bland-Altman analysis further confirmed the high agreement between the model and experienced sonographers., Conclusion: We developed an AI-based model using the nnU-NetV2 architecture for accurate segmentation and automated measurement of critical anatomical structures in fetal four-chamber view images. Our model demonstrated high segmentation accuracy and strong agreement with experienced sonographers in computing clinically relevant parameters. This approach has the potential to improve the efficiency and reliability of prenatal cardiac screening, ultimately contributing to the early detection of congenital heart defects., (© 2024. The Author(s).)

Objectives: This study aims to elucidate the transcriptomic signatures and dysregulated pathways in patients with Systemic Lupus Erythematosus (SLE), with a particular focus on those persisting during disease remission., Methods: We conducted bulk RNA-sequencing of peripheral blood mononuclear cells (PBMCs) from a well-defined cohort comprising 26 remission patients meeting the Low Lupus Disease Activity State (LLDAS) criteria, 76 patients experiencing disease flares, and 15 healthy controls. To elucidate immune signature changes associated with varying disease states, we performed extensive analyses, including the identification of differentially expressed genes and pathways, as well as the construction of protein-protein interaction networks., Results: Several transcriptomic features recovered during remission compared to the active disease state, including down-regulation of plasma and cell cycle signatures, as well as up-regulation of lymphocytes. However, specific innate immune response signatures, such as the interferon (IFN) signature, and gene modules involved in chromatin structure modification, persisted across different disease states. Drug repurposing analysis revealed certain drug classes that can target these persistent signatures, potentially preventing disease relapse., Conclusion: Our comprehensive transcriptomic study revealed gene expression signatures for SLE in both active and remission states. The discovery of gene expression modules persisting in the remission stage may shed light on the underlying mechanisms of vulnerability to relapse in these patients, providing valuable insights for their treatment., (© 2024. The Author(s).)

Background: Periodontitis represents the foremost oral condition in young men, strongly correlated with socioeconomic elements and oral health behaviors. This research aimed to assess the prevalence of periodontitis and associated associations with socio-demographics and oral health practices for subsequent Hazard Ratio (HR) estimation., Methods: A total of 46,476 young men were recruited to the study between August 2022 and October 2023. A questionnaire on socio-demographic factors and oral health-related behaviors related to periodontitis was completed. The standard procedure was used for oral examination. Logistic regression and hazard ratios were used to estimate the influencing factors, whereas the nomogram was used to predict the risk of periodontitis in young men., Results: A total of 46,476 young men were surveyed and completed the questionnaire. The overall prevalence of periodontitis among young men was 1.74%. Out of these, 1.7% had mild periodontitis and 0.6% had moderate periodontitis. Age and dental calculus were important factors in the periodontal health of young men. This nomogram, which includes 7 easily obtainable clinical characteristics routinely collected during periodontitis risk assessment, provides clinicians with a user-friendly tool to assess the risk of periodontal disease in young men., Conclusions: Regular dental prophylaxis is crucial for young men to maintain their gingival health and prevent the onset of periodontitis. Dental calculus plays a prominent role in this matter, as it serves as a significant contributing factor., (© 2024. The Author(s).)

Background: Fusobacterium nucleatum (F. nucleatum) is a microbial risk factor whose presence increases the risk of oral squamous cell carcinoma (OSCC) progression. However, whether it can promote the proliferation of OSCC cells remains unknown., Methods: In this study, we investigated F. nucleatum effect on OSCC cell proliferation using in vitro and in vivo experiments., Results: Our results showed that F. nucleatum promoted OSCC cell proliferation, doubling the cell count after 72 h (CCK-8 assay). Cell cycle analysis revealed G2/M phase arrest. F. nucleatum interaction with CDH1 triggered phosphorylation, upregulating downstream protein β-catenin and activating cyclinD1 and Myc. Notably, F. nucleatum did not affect noncancerous cells, unrelated to CDH1 expression levels in CAL27 cells. Overexpression of phosphorylated CDH1 in 293T cells did not upregulate β-catenin and cycle-related genes. In vivo BALB/c nude experiments showed increased tumor volume and Ki-67 proliferation index after F. nucleatum intervention., Conclusion: Our study suggests that F. nucleatum promotes OSCC cell proliferation through the CDH1/β-catenin pathway, advancing our understanding of its role in OSCC progression and highlighting its potential as a therapeutic target., (© 2024. The Author(s).)

Arginine, which is metabolized into ornithine, proline, and nitric oxide, plays an important role in embryonic development. The present study was conducted to investigate the molecular mechanism of arginine in proliferation, differentiation, and physiological function of porcine trophoblast cells (pTr2) through metabolic pathways. The results showed that arginine significantly increased cell viability (P < 0.05). The addition of arginine had a quadratic tendency to increase the content of progesterone (P = 0.06) and protein synthesis rate (P = 0.03), in which the maximum protein synthesis rate was observed at 0.4 mM arginine. Arginine quadratically increased (P < 0.05) the intracellular contents of spermine, spermidine and putrescine, as well as linearly increased (P < 0.05) the intracellular content of NO in a dose-dependent manner. Arginine showed a quadratic tendency to increase the content of putrescine (P = 0.07) and a linear tendency to increase NO content (P = 0.09) in cell supernatant. Moreover, increasing arginine activated (P < 0.05) the mRNA expressions for ARG, ODC, iNOS and PCNA. Furthermore, inhibitors of arginine metabolism (L-NMMA and DFMO) both inhibited cell proliferation, while addition of its metabolites (NO and putrescine) promoted the cell proliferation and cell cycle, the mRNA expressions of PCNA, EGF and IGF-1, and increased (P < 0.05) cellular protein synthesis rate, as well as estradiol and hCG secretion (P < 0.05). In conclusion, our results suggested that arginine could promote cell proliferation and physiological function by regulating the metabolic pathway. Further studies showed that arginine and its metabolites modulate cell function mainly through β-catenin and mTOR pathways., (© 2024. The Author(s).)