IGF2BP2 inhibits invasion and migration of clear cell renal cell carcinoma via targeting Netrin-4 in an m6A-dependent manner.

Clear cell renal cell carcinoma (ccRCC), the most common subtype of renal cell carcinoma, often leads to a poor prognosis due to metastasis. The investigation of N6-methyladenosine (m6A) methylation, a crucial RNA modification, and its role in ccRCC, particularly through the m6A reader insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2), revealed significant insights. We found that IGF2BP2 was notably downregulated in ccRCC, which correlated with tumor aggressiveness and poor prognosis. Thus, IGFBP2 has emerged as an independent prognostic factor of ccRCC. Moreover, a strong positive correlation was observed between the expression of IGF2BP2 and Netrin-4. Netrin-4 was also downregulated in ccRCC, and its lower levels were associated with increased malignancy and poor prognosis. Overexpression of IGF2BP2 and Netrin-4 suppressed the invasion and migration of ccRCC cells, while Netrin-4 knockdown reversed these effects in ccRCC cell lines. RNA immunoprecipitation (RIP)-quantitative polymerase chain reaction validated the robust enrichment of Netrin-4 mRNA in anti-IGF2BP2 antibody immunoprecipitates. MeRlP showed significantly increased Netrin4 m6A levels after lGF2BP2 overexpression. Moreover, we found that IGF2BP2 recognized and bound to the m6A site within the coding sequence of Netrin-4, enhancing its mRNA stability. Collectively, these results showed that IGF2BP2 plays a suppressive role in the invasion and migration of ccRCC cells by targeting Netrin-4 in an m6A-dependent manner. These findings underscore the potential of IGF2BP2/Netrin-4 as a promising prognostic biomarker and therapeutic target in patients with ccRCC metastasis.

Drivers of interlineage variability in mitogenomic evolutionary rates in Platyhelminthes.

Studies of forces driving interlineage variability in the evolutionary rates (both sequence and architecture) of mitochondrial genomes often produce contradictory results. Flatworms (Platyhelminthes) exhibit the fastest-evolving mitogenomic sequences among all bilaterian phyla. To test the effects of multiple factors previously associated with different aspects of mitogenomic evolution, we used mitogenomes of 223 flatworm species, phylogenetic multilevel regression models, and causal inference. Thermic host environment (endothermic vs. ectothermic) had nonsignificant impacts on both sequence evolution and mitogenomic size. Mitogenomic gene order rearrangements (GORR) were mostly positively correlated with mitogenomic size (R2 ≈ 20-30%). Longevity was not (negatively) correlated with sequence evolution in flatworms. The predominantly free-living "turbellaria" exhibited much shorter branches and faster-evolving mitogenomic architecture than parasitic Neodermata. As a result, "parasitism" had a strong explanatory power on the branch length variability (>90%), and there was a negative correlation between GORR and branch length. However, the stem branch of Neodermata comprised 63.6% of the total average branch length. This evolutionary period was also marked by a high rate of gene order rearrangements in the ancestral Neodermata. We discuss how this period of rapid evolution deep in the evolutionary history may have decoupled sequence evolution rates from longevity and GORR, and overestimated the explanatory power of "parasitism". This study shows that impacts of variables often vary across lineages, and stresses the importance accounting for the episodic nature of evolutionary patterns in studies of mitogenomic evolution.

Changes of intestinal barrier in the process of intestinal inflammation induced by Aeromonas hydrophila in snakehead (Channa argus).

Bacterial intestinal inflammation frequently occurs in cultured fish. Nevertheless, research on intestinal barrier dysfunction in the process of intestinal inflammation is deficient. In this study, we explored the changes of intestinal inflammation induced by Aeromonas hydrophila (A. hydrophila) in snakehead and the relationship between intestinal barrier and inflammation. Snakehead [(13.05 ± 2.39) g] were infected via anus with A. hydrophila. Specimens were collected for analysis at 0, 1, 3, 7 and 21 d post-injection. The results showed that with the increase of exposure time, the hindgut underwent stages of normal function, damage, damage deterioration, repair and recovery. Relative to 0 d, the levels of IL-1ß and TNF-α in serum, and the expression of nod1, tlr1, tlr5, nf-κb, tnf-α and il-1ß in intestine were significantly increased, and showed an upward then downward pattern over time. However, the expression of tlr2 and il-10 were markedly decreased, and showed the opposite trend. In addition, with the development of intestinal inflammation, the diversity and richness of species, and the levels of phylum and genus in intestine were obviously altered. The levels of trypsin, LPS, AMS, T-SOD, CAT, GPx, AKP, LZM and C3 in intestine were markedly reduced, and displayed a trend of first decreasing and then rebounding. The ultrastructure observation showed that the microvilli and tight junction structure of intestinal epithelial cells experienced normal function initially, then damage, and finally recovery over time. The expression of claudin-3 and zo-1 in intestine were significantly decreased, and showed a trend of first decreasing and then rebounding. Conversely, the expression of mhc-i, igm, igt and pigr in intestine were markedly increased, and displayed a trend of increasing first and then decreasing. The above results revealed the changes in intestinal barrier during the occurrence and development of intestinal inflammation, which provided a theoretical basis for explaining the relationship between the two.

PD-L2 mediates tobacco smoking-induced recruitment of regulatory T cells via the RGMB/NFκB/CCL20 cascade.

Programmed cell death ligand 2 (PD-L2), a ligand for the receptor programmed cell death 1 (PD-1), has an identity of 34% with its twin ligand PD-L1 and exhibits higher binding affinity with PD-1 than PD-L1. However, the role of PD-L2 in non-small cell lung cancer (NSCLC) progression, especially tobacco-induced cancer progression, has not been fully understood. Here, we found that PD-L2 promoted tumor growth in murine models with recruitment of regulatory T cells (Tregs). In patients with NSCLC, PD-L2 expression level in tumor samples was higher than in counterpart normal controls and was positively associated with patients' response to anti-PD-1 treatment. Mechanismly, PD-L2 bound its receptor Repulsive guidance molecule B (RGMB) on cancer cells and activated extracellular signal-regulated kinase (Erk) and nuclear factor κB (NFκB), leading to increased production of chemokine CCL20, which recruited Tregs and contributed to NSCLC progression. Consistently, knockdown of RGMB or NFκB p65 inhibited PD-L2-induced CCL20 production, and silencing of PD-L2 repressed Treg recruitment by NSCLC cells. Furthermore, cigarette smoke and carcinogen benzo(a)pyrene (BaP) upregulated PD-L2 in lung epithelial cells via aryl hydrocarbon receptor (AhR)-mediated transcription activation, whose deficiency markedly suppressed BaP-induced PD-L2 upregulation. These results suggest that PD-L2 mediates tobacco-induced recruitment of Tregs via the RGMB/NFκB/CCL20 cascade, and targeting this pathway might have therapeutic potentials in NSCLC.

The ratio of neutrophils to lymphocytes effectively predicts clinical outcomes in idiopathic membranous nephropathy.

BACKGROUND: Systemic inflammatory indicators are important in the prognoses of various diseases. Such indicators, including the neutrophil-to-lymphocyte ratio (NLR), can be meaningful in predicting the clinical outcome in patients diagnosed with idiopathic membranous nephropathy (IMN). MATERIALS AND METHODS: 112 IMN patients diagnosed by renal biopsy were recruited retrospectively. The endpoint was defined as a combination of partial and complete remission. Statistical analysis determined the independent factors associated with clinical remission and the predictive utility of NLR. RESULTS: Within the 12-month follow-up period, 72 patients achieved clinical remission after treatment. Univariate analysis identified significant differences in serum albumin, estimated glomerular filtration rate (eGFR), proteinuria, neutrophil count, and NLR between the remission group and the non-remission group (all p < 0.05). Cox proportional hazards indicated that elevated eGFR (HR 1.022, 95% CI (1.009 - 1.035), p = 0.001), lower NLR (HR 0.345, 95% CI (0.237 - 0.501), p = 0.0001), and decreased proteinuria (HR 0.826, 95% CI (0.693 - 0.984), p = 0.032) were protective elements for remission. With an optimal cut-off value of 2.61, the pre-treatment NLR had an excellent ability to identify the remission (area under the curve (AUC), 0.785). Participants were separated into low- and high-NLR groups by using 2.61. Kaplan-Meier survival curves revealed significantly higher remission rates in the lower group (p < 0.0001). CONCLUSION: The NLR is an effective indicator for predicting clinical remission in patients with IMN.

Roxadustat Versus Erythropoietin: The Comparison of Efficacy in Reversing Ventricular Remodeling in Dialysis Patients with Anaemia.

Background: Renal anaemia and left ventricular hypertrophy are the main complications of chronic kidney disease and are shared among dialysis patients. This retrospective study aimed to compare the efficacies of the hypoxia-inducible factor prolyl hydroxylase inhibitor roxadustat and recombinant human erythropoietin in reversing ventricular remodeling in dialysis patients with renal anaemia. Methods: A total of 204 participants underwent baseline examinations, including echocardiograms and laboratory tests, before being administered either treatment for at least 24 weeks from January 2018 to October 2021, after which follow-up examinations were conducted at 6 months. Propensity score matching based on key variables included age, gender, cardiovascular diseases, cardiovascular medications, dialysis course and the vascular access at baseline was performed to include populations with similar characteristics between groups. Results: In total, 136 patients were included with roxadustat or recombinant human erythropoietin. The left ventricular mass index after treatment with roxadustat and recombinant human erythropoietin both significantly decreased after 6 months, but there was no significant difference in the change in left ventricular mass index between the two groups. In addition, the left ventricular end-diastolic diameters and left ventricular wall thickness, systolic blood pressure, and diastolic blood pressure significantly decreased in the roxadustat group. Roxadustat and recombinant human erythropoietin also increased haemoglobin significantly, but there was no significant difference in the change in haemoglobin between the two groups. The results of multiple linear regression showed that the change in haemoglobin was independent factor affecting the improvement of left ventricular mass index. Conclusions: The increase of haemoglobin was associated with improving left ventricular hypertrophy in dialysis patients. However, the beneficial effects between roxadustat and recombinant human erythropoietin on left ventricular mass index did not show clear superiority or inferiority in six months.

Multi-instance learning based artificial intelligence model to assist vocal fold leukoplakia diagnosis: A multicentre diagnostic study.

OBJECTIVE: To develop a multi-instance learning (MIL) based artificial intelligence (AI)-assisted diagnosis models by using laryngoscopic images to differentiate benign and malignant vocal fold leukoplakia (VFL). METHODS: The AI system was developed, trained and validated on 5362 images of 551 patients from three hospitals. Automated regions of interest (ROI) segmentation algorithm was utilized to construct image-level features. MIL was used to fusion image level results to patient level features, then the extracted features were modeled by seven machine learning algorithms. Finally, we evaluated the image level and patient level results. Additionally, 50 videos of VFL were prospectively gathered to assess the system's real-time diagnostic capabilities. A human-machine comparison database was also constructed to compare the diagnostic performance of otolaryngologists with and without AI assistance. RESULTS: In internal and external validation sets, the maximum area under the curve (AUC) for image level segmentation models was 0.775 (95 % CI 0.740-0.811) and 0.720 (95 % CI 0.684-0.756), respectively. Utilizing a MIL-based fusion strategy, the AUC at the patient level increased to 0.869 (95 % CI 0.798-0.940) and 0.851 (95 % CI 0.756-0.945). For real-time video diagnosis, the maximum AUC at the patient level reached 0.850 (95 % CI, 0.743-0.957). With AI assistance, the AUC improved from 0.720 (95 % CI 0.682-0.755) to 0.808 (95 % CI 0.775-0.839) for senior otolaryngologists and from 0.647 (95 % CI 0.608-0.686) to 0.807 (95 % CI 0.773-0.837) for junior otolaryngologists. CONCLUSIONS: The MIL based AI-assisted diagnosis system can significantly improve the diagnostic performance of otolaryngologists for VFL and help to make proper clinical decisions.

[Mechanism of Huangqin Qingre Chubi Capsules regulating p53/p21 signaling pathway to delay chondrocyte senescence in osteoarthritic rats].

This study aims to investigate the mechanism of Huangqin Qingre Chubi Capsules(HQC) in delaying chondrocyte senescence of osteoarthritic(OA) rats by regulating the p53/p21 signaling pathway. Rheumatic fever paralysis models of OA rats were induced based on monosodiun iodoacetate(MIA) combined with external rheumatic fever environmental stimuli and divided into normal(Con) group, OA model(MIA) group, OA model+rheumatic fever stimulation model(MIA-M) group, MIA-M+HQC low-dose(MIA-M+HQC-L) group, medium-dose(MIA-M+HQC-M) group, and high-dose(MIA-M+HQC-H) group, and MIA-M+glucosamine(MIA-M+GS) group. The models were successfully prepared and administered by gavage for 30 d. The pathological changes of cartilage were observed by hematoxylin-eosin(HE) and Senna O solid green(SO) staining. The expression of interleukin(IL)-1ß and IL-6 was detected by enzyme-linked immunosorbent assay(ELISA). Flow cytometry(FCM) was used to detect apoptosis and cell cycle. The mRNA expression of MMP13, ADAMTS-5, COLⅡ, and TGF-ß was detected by RT-qPCR. The protein expression of p53/p21, p16, Bax, and Bcl-2 was detected by Western blot. The articular cartilage surface of rats in the Con group was smooth, and the tide line was smooth. The cartilage layer of MIA and MIA-M groups was obviously damaged, and the cartilage matrix was reduced. The above conditions were more severe in the MIA-M group. The cartilage surface of the HQC high-dose group and MIA-M+GS group was basically intact with clear delamination. Compared with the MIA-M+HQC-H group, Mankin's score was higher in the HQC low-dose and medium-dose groups, and the change was not obvious in the MIA-M+GS group. Compared with the Con group, the proportion of chondrocytes G_1 was elevated in the MIA and MIA-M groups, and the proportion of the S phase and G_2 phase was significantly decreased. In addition, the apoptosis rate was increased. Compared with MIA-M, HQC groups inhibited apoptosis and promoted cell proliferation in a concentration-dependent manner. Compared with the MIA-M+HQC-H group, the effect was more significant in the HQC high-dose group than in the HQC medium-low dose, while it was not significant in the MIA-M+GS group. Compared with the Con group, IL-1ß and IL-6 were elevated in the MIA and MIA-M groups, and mRNA levels of MMP13 and ADAMTS-5 were elevated. p53, p21, p16, and Bax protein were elevated, and mRNA levels of COLⅡ and TGF-ß were decreased. Compared with the MIA-M group, IL-1ß and IL-6 decreased after drug interventions of HQC and GS, and mRNA levels of MMP13 and ADAMTS-5, as well as protein levels of p53, p21, Bax, and p16 decreased. In addition, Bcl-2 increased. The improvement of these indexes was significantly better in the MIA-M+HQC-H group than in the HQC low-dose and medium-dose groups, and the difference with the MIA-M+GS group was not significant. HQC delayed MIA-induced chondrocyte senescence in OA rats, inhibited inflammatory response and extracellular matrix(ECM) degradation, and its mechanism may be related to the inhibition of the p53/p21 pathway.

Mutagenesis of Odorant Receptor Coreceptor Orco Reveals the Odorant-Detected Behavior of the Predator Eupeodes corollae.

The successful mating of the hoverfly and the search for prey aphids are of great significance for biological control and are usually mediated by chemical cues. The odorant receptor co-receptor (Orco) genes play a crucial role in the process of insect odor perception. However, the function of Orco in the mating and prey-seeking behaviors of the hoverfly remains relatively unexplored. In this study, we characterized the Orco gene from the hoverfly, Eupeodes corollae, a natural enemy insect. We used the CRISPR/Cas9 technique to knock out the Orco gene of E. corollae, and the EcorOrco-/- homozygous mutant was verified by the genotype analysis. Fluorescence in situ hybridization showed that the antennal ORN of EcorOrco-/- mutant lack Orco staining. Electroantennogram (EAG) results showed that the adult mutant almost lost the electrophysiological response to 15 odorants from three types. The two-way choice assay and the glass Y-tube olfactometer indicated that both the larvae and adults of hoverflies lost their behavioral preference to the aphid alarm pheromone (E)-ß-farnesene (EBF). In addition, the mating assay results showed a significant decrease in the mating rate of males following the knock out of the EcorOrco gene. Although the mating of females was not affected, the amount of eggs being laid and the hatching rate of the eggs were significantly reduced. These results indicated that the EcorOrco gene was not only involved in the detection of semiochemicals in hoverflies but also plays a pivotal role in the development of eggs. In conclusion, our results expand the comprehension of the chemoreceptive mechanisms in the hoverflies and offers valuable insights for the advancement of more sophisticated pest management strategies.

Dry Reforming of Methane on Ni/LaZrO2 Catalyst under External Electric Fields: A Combined First-Principles and Microkinetic Modeling Study.

Dry reforming of methane (DRM) reaction has great potential in reducing the greenhouse effect and solving energy problems. Herein, the DRM reaction mechanism and activity on Ni16/LaZrO2 catalyst under electric fields were comprehensively investigated by combining density functional theory calculations with microkinetic modeling. The results showed that La doping increases the interaction between Ni and ZrO2 by Ni cluster transfer of more electrons. The adsorption strength of species followed the order Ni16/ZrO2 > Ni16/LaZrO2, which is consistent with the results for the d-band center but opposite to the metal-support interaction. The best DRM reaction path on Ni16/LaZrO2 was the CH2-O pathway, which is different from the CH-O pathway on Ni(111) and Ni16/ZrO2. Both positive and negative electric fields of strong and weak metal-support interactions reduced the energy barrier of DRM reaction. Importantly, our results showed that the more dispersed and smaller Ni12/LaZrO2 model by considering the dispersing effect induced by La doping, which displayed very different results from that of Ni16/LaZrO2: reduced the energy barrier for methane decomposition, thereby promoting DRM reaction activity. Microkinetic results showed that the carbon deposition behavior of DRM becomes weaker on Ni16/LaZrO2 due to the suppression of methane decomposition in the presence of La doping compared to Ni16/ZrO2, but the opposite result is obtained on Ni12/LaZrO2. The order of DRM reactivity was Ni16/LaZrO2 < Ni16/ZrO2 < Ni12/LaZrO2, which is consistent with the experiment observations. The conversion of methane and CO2 was higher in positive electric fields than in negative electric fields at low temperatures, but the results were opposite at high temperature. Negative electric fields can improve the carbon deposition resistance of Ni-based catalysts compared to positive electric fields. The degree of rate control analysis showed that CHx* oxidation also plays an important role in the DRM reaction. We envision that this study could provide a deeper understanding for guiding the widespread application of electric field catalysis.

Clarifying the relationship and analyzing the influential factors of bronchial asthma in children with attention-deficit hyperactivity disorder.

BACKGROUND: Bronchial asthma is closely related to the occurrence of attention-deficit hyperactivity disorder (ADHD) in children, which can easily have adverse effects on children's learning and social interactions. Studies have shown that childhood asthma can increase the risk of ADHD and the core symptoms of ADHD. Compared with children with ADHD alone, children with asthma and ADHD are more likely to show high levels of hyperactivity, hyperactive-impulsive and other externalizing behaviors and anxiety in clinical practice and have more symptoms of somatization and emotional internalization. AIM: To explore the relationship between ADHD in children and bronchial asthma and to analyze its influencing factors. METHODS: This retrospective cohort study was conducted at Dongying People's Hospital from September 2018 to August 2023. Children diagnosed with ADHD at this hospital were selected as the ADHD group, while healthy children without ADHD who underwent physical examinations during the same period served as the control group. Clinical and parental data were collected for all participating children, and multivariate logistic regression analysis was employed to identify risk factors for comorbid asthma in children with ADHD. RESULTS: Significant differences were detected between the ADHD group and the control group in terms of family history of asthma and allergic diseases, maternal complications during pregnancy, maternal use of asthma and allergy medications during pregnancy, maternal anxiety and depression during pregnancy, and parental relationship status (P < 0.05). Out of the 183 children in the ADHD group, 25 had comorbid asthma, resulting in a comorbidity rate of 13.66% (25/183), compared to the comorbidity rate of 2.91% (16/549) among the 549 children in the control group. The difference in the asthma comorbidity rate between the two groups was statistically significant (P < 0.05). The results of the multivariate logistic regression analysis indicated that family history of asthma and allergic diseases, maternal complications during pregnancy, maternal use of asthma and allergy medications during pregnancy, maternal anxiety and depression during pregnancy, and parental relationship status are independent risk factors increasing the risk of comorbid asthma in children with ADHD (P < 0.05). CONCLUSION: Children with ADHD were more likely to have comorbid asthma than healthy control children were. A family history of asthma, adverse maternal factors during pregnancy, and parental relationship status were identified as risk factors influencing the comorbidity of asthma in children with ADHD. Clinically, targeted interventions based on these factors can be implemented to reduce the risk of comorbid asthma. This information is relevant for results sections of abstracts in scientific articles.

Programming viscoelastic properties in a complexation gel composite by utilizing entropy-driven topologically frustrated dynamical state.

Hydrogel composites in an aqueous media with viscoelastic properties and elastic modulus that can be precisely tailored are desirable to mimic many biological tissues ranging from mucus, vitreous humor, and nucleus pulposus as well as build up biosensors. Without altering the chemistry, tuning the physical interactions and structures to govern the viscoelastic properties of the hydrogels is indispensable for their applications but quite limited. Here we design a complexation gel composite and utilize the physical principle of topologically frustrated dynamical state to tune the correlated structures between the guest polycation chains and negatively charged host gels. We precisely quantify the mesh size of the host gel and guest chain size. By designing various topologically correlated structures, a viscoelastic moduli map can be built up, ranging from tough to ultrasoft, and from elastic-like with low damping properties to viscous-like with high damping properties. We also tune the swelling ratio by using entropy effect and discover an Entropy-driven Topologically Isovolumetric Point. Our findings provide essential physics to understand the relationship between entropy-driven correlated structures and their viscoelastic properties of the complexation hydrogel composites and will have diverse applications in tissue engineering and soft biomaterials.

Mechanistic investigation of methanol-to-olefins conversion catalyzed by H-ZSM-5 zeolite: a DFT study.

CONTEXT: The mechanisms for the formation of the first C - C bond and lower olefins on methanol to olefins (MTO) conversion on H-ZSM-5 had been focused in dispute. In this paper, density functional theory has been used to study the reaction mechanisms of methanol to olefins on ZSM-5. The configurations of reactants, intermediates, products and transition state of the numerous reactions involved in such a process have been optimized, as well as the elementary reactions related to these configurations were determined by the calculation of corresponding activation energy barriers and reaction heats. Here, two different kinds of the mechanisms were proposed for the formation of dimethyl ether (DME), one involving an associative interaction of two methanol molecules with the zeolite Brønsted acid sites and the other occurring via a surface methoxy species and a methanol molecule. A critical intermediate of the methoxy methyl cation was theoretically verified by the reaction of the methoxy species and dimethyl ether. Besides, it was found that the first intermediates containing a C - C bond were 1,2-dimethoxyethane and 2-methoxy-ethanolare, in which the former was formed from methoxy species with dimethyl ether and the latter was formed from methanol by onium ions((CH3)2O+CH2CH2OCH3), respectively. For the whole reaction mechanism, the results in this paper indicated that the ethene formation is more favorable than propylene formation due to the low activation energy barrier for ethene formation (123.49 vs. 162.09 kJ.mol-1). From these calculations, it would be concluded that ethene is the first alkene product that induces the occurrence of the hydrocarbon pool mechanism. METHODS: All the periodic density function theory (DFT) calculations were performed by the Vienna Ab Initio Simulation package (VASP). The interaction between nucleus and valence electron was described using the pseudopotentials found in the projector augmented wave (PAW) method. PBE-D3 was used in the whole DFT calculations and CI-NEB was used to locate transition state.

Analysis of bioprinting strategies for skin diseases and injuries through structural and temporal dynamics: historical perspectives, research hotspots, and emerging trends.

This study endeavors to investigate the progression, research focal points, and budding trends in the realm of skin bioprinting over the past decade from a structural and temporal dynamics standpoint. Scholarly articles on skin bioprinting were obtained from WoSCC. A series of bibliometric tools comprising R software, CiteSpace, HistCite, and an alluvial generator were employed to discern historical characteristics, evolution of active topics, and upcoming tendencies in the area of skin bioprinting. Over the past decade, there has been a consistent rise in research interest in skin bioprinting, accompanied by an extensive array of meaningful scientific collaborations. Concurrently, diverse dynamic topics have emerged during various periods, as substantiated by an aggregate of 22 disciplines, 74 keywords, and 187 references demonstrating citation bursts. Four burgeoning research subfields were discerned through keyword clustering-namely, #3 'in situbioprinting', #6 'vascular', #7 'xanthan gum', and #8 'collagen hydrogels'. The keyword alluvial map reveals that Module 1, including 'transplantation' etc, has primarily dominated the research module over the previous decade, maintaining enduring relevance despite annual shifts in keyword focus. Additionally, we mapped out the top six key modules from 2023 being 'silk fibroin nanofiber', 'system', 'ionic liquid', 'mechanism', and 'foot ulcer'. Three recent research subdivisions were identified via timeline visualization of references, particularly Clusters #0 'wound healing', #4 'situ mineralization', and #5 '3D bioprinter'. Insights derived from bibliometric analyses illustrate present conditions and trends in skin bioprinting research, potentially aiding researchers in pinpointing central themes and pioneering novel investigative approaches in this field.

A comprehensive analysis of the prognostic characteristics of microRNAs in breast cancer.

Both overall survival (OS) and disease-specific survival (DSS) are significant when determining a patient's prognosis for breast cancer (BC). The effect of DSS-related microRNAs on BC susrvival, however, is not well understood. Here, we spotted differentially expressed miRNAs (DEMs) in the TCGA database of BC DSS, identified eight DSS-related miRNAs, and constructed a risk model. AUC values at 1, 3, and 5 years were 0.852, 0.861, and 0.868, respectively, indicating a risk model's excellent prognostic prediction ability. Then, we validated miRNA roles in BC OS and finally defined miR-551b as an independently prognostic miRNA in BC. According to function analysis, miR-551b is strongly linked with the emergence and spread of cancer, including protein ubiquitination, intracellular protein transport, metabolic pathways, and cancer pathways. Moreover, we confirmed the low expression of miR-551b in BC tissue and cells. After miR-551b inhibition or overexpression, cell function was either dramatically increased or diminished, respectively, indicating that miR-551b could regulate BC proliferation, invasion, and migration. In conclusion, we thoroughly clarified BC-related miRNAs on DSS and OS and verified miR-551b as a crucial regulator in the development and prognosis of cancer. These results can offer fresh ideas for BC therapy.

Incidence and clinical analysis of asymptomatic intracranial hemorrhage in neonates with cerebral hypoxic-ischaemic risk based on multisequence MR images.

The incidence and clinical distribution of intracranial haemorrhage (ICH) in neonates at risk of cerebral hypoxia-ischaemia have not been reported in specific studies. Based on conventional magnetic resonance imaging (MRI) versus susceptibility weighted imaging (SWI), this study aimed to analyse the occurrence of asymptomatic ICH in newborns with or without risk of cerebral hypoxia-ischaemia and to accumulate objective data for clinical evaluations of high-risk neonates and corresponding response strategies. 317 newborns were included. MRI revealed that the overall incidence of ICH was 59.31%. The most common subtype was intracranial extracerebral haemorrhage (ICECH) which included subarachnoid haemorrhage (SAH) and subdural haemorrhage (SDH). ICECH accounted for 92.02% of ICH. The positive detection rate of ICECH by SWI was significantly higher than that by T1WI. The incidence of total ICH, ICECH and SAH was greater among children who were delivered vaginally than among those who underwent caesarean delivery. Asymptomatic neonatal ICH may be a common complication of the neonatal birth process, and SWI may improve the detection rate. Transvaginal delivery and a weight greater than 2500 g were associated with a high incidence of ICECH in neonates. The impact of neonatal cerebral hypoxia-ischaemia risk factors on the occurrence of asymptomatic ICH may be negligible.

Pathological mechanism of immune disorders in diabetic kidney disease and intervention strategies.

Diabetic kidney disease is one of the most severe chronic microvascular complications of diabetes and a primary cause of end-stage renal disease. Clinical studies have shown that renal inflammation is a key factor determining kidney damage during diabetes. With the development of immunological technology, many studies have shown that diabetic nephropathy is an immune complex disease, and that most patients have immune dysfunction. However, the immune response associated with diabetic nephropathy and autoimmune kidney disease, or caused by ischemia or infection with acute renal injury, is different, and has a com-plicated pathological mechanism. In this review, we discuss the pathogenesis of diabetic nephropathy in immune disorders and the intervention mechanism, to provide guidance and advice for early intervention and treatment of diabetic nephropathy.

The long non-coding RNA mir155hg promotes NLRP3-inflammasome activation and oxidative stress response in acute lung injury by targeting miR-450b-5p to regulate HIF-1α.

BACKGROUND: Acute lung injury (ALI) can cause multiple organ dysfunction and a high mortality rate. Inflammatory responses, oxidative stress, and immune damage contribute to their pathogenic mechanisms. We studied the role of the newly discovered lncRNA, Lncmir155hg, in ALI. METHODS: The levels of Lncmir155hg and miR-450b-5p from mice with ALI were detected via polymerase chain reaction analysis (qRT-PCR) and Fluorescence in situ hybridization (FISH). Pathological changes of lung were detected by HE (hematoxylin and eosin) staining, and HIF-1α, NOD-like receptor 3 (NLRP3) and caspase-1 protein changes were detected by immunohistochemistry. MLE-12 cells proliferation was detected by Cell-Counting Kit 8 analysis, and reactive oxygen species (ROS) was detected via flow cytometry. NLRP3, apoptosis-associated speck-like protein (ASC), and caspase-1 were measured via western blotting, and enzyme-linked immunosorbent assays detected the expression of Inflammatory factors. Lncmir155hg, miR-450b-5p, miR-450b-5p, and HIF-1α targets were predicted using LncTar and miRWalk and confirmed in dual-luciferase reporter assays. RESULTS: In mice with ALI and MLE-12 cells induced by lipopolysaccharide (LPS), Lncmir155hg was high-expressed and miR-450b-5p was low-expressed. sh-Lncmir155hg reduced the damage of lung tissue, the production of inflammatory cytokines and oxidative stress reaction induced by LPS，miR-450b-5p reverses the effect of Lncmir155hg in mice. sh-Lncmir155hg decreased the protein levels of HIF-1α, NLRP3 and caspase-1 in LPS-induced lung tissues. sh-Lncmir155hg + miR-450b-5p inhibitor transfection reversed the effect of sh-Lncmir155hg on the expression of HIF-1α, NLRP3 and caspase-1. Lncmir155hg knockdown induced proliferation and inhibited NLRP3-inflammasome activation and oxidative stress in MLE-12 cells of ALI. miR-450b-5p was identified to have binding with Lncmir155hg, and inhibition of miR-450b-5p eliminated the effect of si-Lncmir155hg in MLE-12 cells of ALI. More importantly, miR-450b-5p was directly combined with HIF-1α, miR-450b-5p mimic promoted proliferation and inhibited activation of inflammasome associated proteins and reaction of oxidative stress, and HIF-1α overexpression abolished these effects. CONCLUSION: Lncmir155hg aggravated ALI via the miR-450b-5p/HIF-1α axis.

Case report: Successful treatment of a rare HER2-positive advanced breast squamous cell carcinoma.

Background: Breast squamous cell carcinoma (SCC) is an uncommon and highly aggressive variant of metaplastic breast cancer. Despite its rarity, there is currently no consensus on treatment guidelines for this specific subtype. Previous studies have demonstrated that chemotherapy alone has limited efficacy in treating breast SCC. However, the potential for targeted therapy in combination with chemotherapy holds promise for future treatment options. Case presentation: In this case report, we present a patient with advanced HER2-positive breast SCC, exhibiting a prominent breast mass, localized ulcers, and metastases in the lungs and brain. Our treatment approach involved the administration of HER2-targeted drugs in conjunction with paclitaxel, resulting in a sustained control of tumor growth. Conclusion: This case represents a rare occurrence of HER2-positive breast SCC, with limited available data on the efficacy of previous HER2-targeted drugs in treating such patients. Our study presents the first application of HER2-targeted drugs in this particular case, offering novel therapeutic insights for future considerations. Additionally, it is imperative to conduct further investigations to assess the feasibility of treatment options in a larger cohort of patients.