Segmentation of the left atrial appendage based on fusion attention.

In clinical practice, the morphology of the left atrial appendage (LAA) plays an important role in the selection of LAA closure devices for LAA closure procedures. The morphology determination is influenced by the segmentation results. The LAA occupies only a small part of the entire 3D medical image, and the segmentation results are more likely to be biased towards the background region, making the segmentation of the LAA challenging. In this paper, we propose a lightweight attention mechanism called fusion attention, which imitates human visual behavior. We process the 3D image of the LAA using a method that involves overview observation followed by detailed observation. In the overview observation stage, the image features are pooled along the three dimensions of length, width, and height. The obtained features from the three dimensions are then separately input into the spatial attention and channel attention modules to learn the regions of interest. In the detailed observation stage, the attention results from the previous stage are fused using element-wise multiplication and combined with the original feature map to enhance feature learning. The fusion attention mechanism was evaluated on a left atrial appendage dataset provided by Liaoning Provincial People's Hospital, resulting in an average Dice coefficient of 0.8855. The results indicate that the fusion attention mechanism achieves better segmentation results on 3D images compared to existing lightweight attention mechanisms.

Slow-Release Effect Assisted Crystallization for Sequential Deposition Realizes Efficient Inverted Perovskite Solar Cells.

The two-step sequential deposition strategy has been widely recognized in promoting the research and application of perovskite solar cells, but the rapid reaction of organic salts with lead iodide inevitably affects the growth of perovskite crystals, accompanied by the generation of more defects. In this study, the regulation of crystal growth was achieved in a two-step deposition method by mixing 1-naphthylmethylammonium bromide (NMABr) with organic salts. The results show that the addition of NMABr effectively delays the aggregation and crystallization behavior of organic salts; thereby, the growth of the optimal crystal (001) orientation of perovskite is promoted. Based on this phenomenon of delaying the crystallization process of perovskite, the "slow-release effect assisted crystallization" is defined. Moreover, the incorporation of the Br element expands the band gap of perovskite and mitigates material defects as nonradiative recombination centers. Consequently, the power conversion efficiency (PCE) of the enhanced perovskite solar cells (PSCs) reaches 20.20%. It is noteworthy that the hydrophobic nature of the naphthalene moiety in NMABr can enhance the humidity resistance of PSCs, and the perovskite phase does not decompose for more than 3000 h (30-40% RH), enabling it to retain 90% of its initial efficiency even after exposure to a nitrogen environment for 1200 h.

[Early effectiveness of local injection of multimodal drug cocktail during anterior cruciate ligament reconstruction and its influence on cartilage].

Objective: To explore the early effectiveness and influence on cartilage of local injection of multimodal drug cocktail (MDC) during anterior cruciate ligament reconstruction (ACLR). Methods: Between February 2022 and August 2023, patients undergone arthroscopic ACLR using autologous hamstring tendons were selected as the study subjects. Among them, 90 patients met the selection criteria and were randomly divided into 3 groups ( n=30) according to the different injection drugs after ligament reconstruction. There was no significant difference in baseline data such as gender, age, body mass index, surgical side, disease duration, preoperative thigh circumference, and preoperative levels of tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), IL-1, matrix metalloproteinase 3 (MMP-3), MMP-13, and aggrecan (ACAN) in synovial fluid between groups ( P>0.05). After the ligament reconstruction during operation, corresponding MDC (consisting of ropivacaine, tranexamic acid, and betamethasone in group A, and ropivacaine, betamethasone, and saline in group B) or saline (group C) were injected into the joint and tendon site, respectively. The length of hospital stay, postoperative tramadol injection volume, incidence of complications, degree of knee joint swelling and range of motion, visual analogue scale (VAS) score, International Knee Documentation Committee (IKDC) score, Lyshlom score, and Hospital for Special Surgery (HSS) score were recorded and compared between groups. The T2 * values in different cartilage regions were detected by MRI examination and the levels of TNF-α, IL-6, IL-1, MMP-3, MMP-13, and ACAN in synovial fluid were detected by ELISA method. Results: The patients in group A, B, and C were followed up (12.53±3.24), (13.14±2.87), and (12.82±3.32) months, respectively. All incisions healed by first intention. Compared with group C, group A and group B had shorter length of hospital stay, less tramadol injection volume, and lower incidence of complications, showing significant differences ( P<0.05); there was no significant difference between group A and group B ( P>0.05). The degree of knee swelling in group A was significantly less than that in group B and group C ( P<0.05), but there was no significant difference between group B and group C ( P>0.05). At 3, 6, 12, 24, and 48 hours after operation, VAS scores of group A and group B were significantly lower than those of group C ( P<0.05); at 72 hours after operation, there was no significant difference among the three groups ( P>0.05). At 3 days, 14 days, and 1 month after operation, the range of motion of knee joint in group A were significantly better than those in group C ( P<0.05), and there was no significant difference between the other groups ( P>0.05). At 1 month after operation, the IKDC score of group A and group B was significantly higher than that of group C ( P<0.05); there was no significant difference among the three groups at other time points ( P>0.05). There was no significant difference in Lyshlom score and HSS score among the three groups at each time point ( P>0.05). At 14 days after operation, the levels of IL-1 and IL-6 in the synovial fluid in groups A and B were significantly lower than those in group C ( P<0.05). There was no significant difference in the levels of TNF-α, MMP-3, MMP-13, and ACAN between groups A and B ( P>0.05). At 1 month after operation, there was no significant difference in the above indicators among the three groups ( P>0.05). At 3, 6, and 12 months after operation, there was no significant difference in the T2 * values of different cartilage regions among the three groups ( P>0.05). Conclusion: Injecting MDC (ropivacaine, tranexamic acid, betamethasone) into the joint and tendon site during ACLR can achieve good early effectiveness without significant impact on cartilage.

Decreasing circ_0014614 promotes the differentiation of bone marrow flineage cells into megakaryocytes in essential thrombocythemia via activiation of miR-138-5p/caspase3 axis.

BACKGROUND: Circular RNAs (circRNA) are pivotal in hematological diseases. Previous study showed that circ_0014614 (circDAP3) was significantly underexpressed in bone marrow-derived exosomes from essential thrombocythemia (ET) patients, affecting the differentiation of bone marrow lineage cells into megakaryocytes. METHODS: Fluorescence in situ hybridization (FISH) was used to display circ_0014614's primary cytoplasmic location in K562 cells. Cytoscape software was used to predict the circRNA-miRNA-mRNA networks, and their expression at the cellular level was detected by Quantitative reverse transcription-polymerase chain reaction (qRT-PCR). qRT-PCR was utilized to detect the expression levels of circ_0014614，miR-138-5p and caspase3 mRNA. Western blot was used to determine the protein levels of GATA-1, RUNX-1, NF-E2, CD41 and caspase3. The proliferation of K562 cells was assessed using the Cell Counting Kit-8 (CCK-8) Assay. Furthermore, the interplay between miR-138-5p and circ_0014614 or caspase3 was elucidated through a Dual-luciferase reporter assay. RESULTS: FISH assay indicated circ_0014614's primary cytoplasmic location in K562 cells. In ET bone marrow and K562 cells, circ_0014614 and caspase3 were down-regulated, whereas miR-138-5p saw a significant surge. Overexpressing circ_0014614 curtailed K562 cells' proliferation and differentiation. Further, circ_0014614 targeted miR-138-5p, with heightened miR-138-5p levels counteracting circ_0014614's inhibition. MiR-138-5p further targeted caspase3, and caspase3 silencing neutralized suppressed miR-138-5p's effects on K562 cell differentiation. CONCLUSION: Circ_0014614 was down-regulated in ET bone marrow and bone marrow lineage cells, and upregulating circ_0014614 can inhibit bone marrow lineage cells' proliferation and differentiation into megakaryocytes. Mechanistically, circ_0014614 functioned as ceRNA via sponging miR-138-5p and alleviated the inhibitory effect of miR-138-5p on its target caspase3, which potentially deters tumor activity in ET.

Expression of nuclear receptor co­activator 7 protein is associated with poor prognosis of breast cancer.

Nuclear receptor coactivator 7 (NCOA7) is an estrogen receptor binding protein. Its role in breast cancer progression has so far remained elusive. The present study aimed to determine the expression levels of NCOA7 in breast tumor samples and confirmed its potential utility as a breast cancer prognostic biomarker. The expression of NCOA7 was detected by immunohistochemical staining in 241 breast cancer tumor samples and 163 adjacent normal tissue samples. The association of NCOA7 expression with the clinicopathological characteristics and overall survival were statistically analyzed. Cell proliferation was determined by Cell Counting Kit-8 and colony-formation assays. Cell migration was detected using wound-healing and Transwell assays. NCOA7 was positively expressed in 44% of breast tumor tissues. The expression of NCOA7 was positively associated with tumor size (T-stage; P=0.005) and lymph node metastasis (N-stage; P=0.008). Additional statistical analysis indicated that the expression of NCOA7 was associated with patient age, tumor size and lymph node metastasis in patients with triple-negative breast cancer (TNBC) compared with that in patients with non-TNBC. The overall survival of patients with NCOA7-positive breast cancer was significantly lower than that of patients with NCOA7-negative breast cancer (P=0.006). Among the patients with lymph node metastasis, the overall survival was reversely associated with the expression of NCOA7 (P=0.042). Furthermore, knockdown of NCOA7 expression in breast cancer T47D and MCF7 cells significantly inhibited both cell proliferation and migration, suggesting that this protein may exert a role in driving breast cancer progression. Taken together, these results indicate that the expression of NCOA7 is associated with poor prognosis of breast cancer and suggest that this protein may be a driver for metastasis and a potential therapeutic target for advanced breast cancer.

Niaodukang Mixture Inhibits Micro-inflammation in CKD Rats by Enhancing MiR-146a Levels in Enterogenous Exosomes.

ETHNOPHARMACOLOGICAL RELEVANCE: The Niaodukang mixture (NDK) is a preparation known for its ability to lower serum creatine levels in individuals with chronic kidney disease (CKD) and is commonly administered at medical facilities like the Zhongshan Hospital of Traditional Chinese Medicine. The initial use of NDK was mainly to treat CKD. Our hospital frequently utilizes NDK, which consists of Rheum officinaleBaill., Salvia miltiorrhiza Bunge., Astragalus aaronii(Eig) Zohary., Carthamus tinctorius L., and Sanguisorba officinalis L., for treating patients with CKD-MBD. It has the effects of eliminating dampness and turbidity and dredging kidney collaterals. However, The impact and process of NDK in chronic kidney disease remain unknown. AIM OF THE STUDY: To determine whether microRNA-146a (miR-146a) is associated with CKD micro-inflammationand whether NDK protects against CKD micro-inflammation by modulating the miR-146a/nuclear factor kappa-B (NF-κB) signaling pathway. MATERIALS AND METHODS: (1) An adenine-induced rat model of chronic kidney disease was created through the use of materials and methods. The levels of miR-146a in exosomes from plasma and ileum were determined by RT-PCR. (2) Human cloned colon adenocarcinoma (Caco-2)cellswere stimulated with lipopolysaccharide (LPS)and transfected with miR-146a mimic and inhibitor. Following that, the western blot and RT-PCR techniques were used to measure the protein and mRNA quantities of Toll-like receptor 4 (TLR4), NF-κB, and TNF receptor-associated factor 6 (TRAF6).(3) Enzyme-linked immunosorbent assay (ELISA) was used to identify serum levels of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α). (4) Plasma exosomes were extracted, and the exosomes in intestinal tissues were extracted via ultrahigh-speed centrifugation.Negative staining electron microscopy was used to analyze the morphology of exosomes and the ultrastructure of intestinal tissue and exosomes. The particle size of the exosomes was measured using nanoparticle tracking analysis. RESULTS: The pathological characteristics of CKD rats included those associated with systemic micro-inflammation, which may be associated with the release of exosomes in intestinal tissue. NDK suppressed the inflammatory response in Caco-2 cells and decreased the levels of IL-1ß, IL-6, and TNF-α in rats with CKD. The expression of miR-146a, which regulates inflammation, differed between plasma-derived and enterogenous exosomes in CKD rats, which may be due to stimulation of ileal exosome release into the blood. NDK effectively reduced the levels of TRAF6, NF-κB, and TLR4 in the ileum tissue of CKD rats. CONCLUSION: NDK can effectively improve micro-inflammation in CKD ratsby enhancing the release of enterogenous exosomes, thereby enhancing the release of exosome-associated miR-146a and inhibiting micro-inflammation.

Clinical efficacy of HI-NPPV in the treatment of AECOPD combined with severe type II respiratory failure. / HI-NPPV治疗AECOPD合并严重II型呼吸衰竭的临床疗效.

OBJECTIVES: Patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) combined with severe type II respiratory failure have a high probability of ventilation failure using conventional non-invasive positive pressure ventilation (NPPV). This study aims to investigate the clinical efficacy of high intensity NPPV (HI-NPPV) for the treatment of AECOPD combined with severe type II respiratory failure. METHODS: The data of patients with AECOPD combined with severe type II respiratory failure (blood gas analysis pH≤7.25) treated with NPPV in the Second Affiliated Hospital of Chongqing Medical University from July 2013 to July 2023 were collected to conduct a retrospective case-control study. The patients were divided into 2 groups according to the inspired positive airway pressure (IPAP) used during the NPPV treatment: a NPPV group (IPAP<20 cmH2O, 1 cmH2O=0.098 kPa) and a HI-NPPV group (20 cmH2O≤IPAP< 30 cmH2O). Ninety-nine and 95 patients were included in the NPPV group and the HI-NPPV group, respectively. A total of 86 pairs of data were matched using propensity score matching (PSM) for data matching. The primary outcome indexes (mortality and tracheal intubation rate) and secondary outcome indexes [blood gas analysis pH, arterial partial pressure of oxygen (PaO2) and arterial partial pressure of carbon dioxide (PaCO2), adverse reaction rate, and length of hospitalization] were compared between the 2 groups. RESULTS: The tracheal intubation rates of the NPPV group and the HI-NPPV group were 6.98% and 1.16%, respectively, and the difference between the 2 groups was statistically significant (χ2=4.32, P<0.05); the mortality of the NPPV group and the HI-NPPV group was 23.26% and 9.30%, respectively, and the difference between the 2 groups was statistically significant (χ2=11.64, P<0.01). The PaO2 at 24 h and 48 h after treatment of the HI-NPPV group was higher than that of the NPPV group, and the PaCO2 of the HI-NPPV group was lower than that of the NPPV group, and the differences were statistically significant (all P<0.05). The differences of pH at 24 h and 48 h after treatment between the 2 groups were not statistically significant (both P>0.05). The differences between the 2 groups in adverse reaction rate and hospitalization length were not statistically significant (both P>0.05). CONCLUSIONS: HI-NPPV can reduce mortality and tracheal intubation rates by rapidly improving the ventilation of patients with AECOPD combined with severe type II respiratory failure. This study provides a new idea for the treatment of patients with AECOPD combined with severe type II respiratory failure.

Independent association between IVC filter placement and VTE risk in patients with upper gastrointestinal bleeding and isolated distal DVT: A retrospective cohort study.

BACKGROUND: The placement of inferior vena cava (IVC) filters often emerges as an alternative preventative measure against pulmonary embolism in patients with upper gastrointestinal (GI) bleeding and isolated distal deep vein thrombosis (DVT). We aimed to investigate the association of IVC filter placement and the incidence of venous thromboembolism (VTE) recurrence in this patient population. METHODS: We performed a retrospective cohort study including 450 patients with upper GI bleeding and isolated distal DVT. Propensity score matching using logistic regression was conducted to mitigate potential selection bias. Logistic regression models and additional sensitivity analyses were conducted to estimate the association between IVC filter implantation and VTE recurrence. Interaction and stratified analyses were also performed according to the background covariates. RESULTS: Patients who underwent IVC filter placement were significantly younger than patients in the surveillance group (55.8 ± 9.0 vs 58.4 ± 11.2 years, p = 0.034). Patients in the IVC filter group demonstrated a higher distal thrombus burden. The VTE recurrence composite was significantly higher in patients who underwent IVC filter placement (44.1% [45/102] vs 25% [87/348], p < 0.001). Unmatched crude logistic regression analysis identified a significant association between IVC filter placement and VTE recurrence composite (OR = 2.37; 95% CI, 1.50-3.75). Sensitivity analyses yielded congruent outcomes. CONCLUSION: This study revealed an increased risk of VTE recurrence among patients receiving IVC filter placement, suggesting that IVC filter placement may not be suitable as a primary treatment for patients with upper GI bleeding and isolated distal DVT.

Incorporating machine learning and PPI networks to identify mitochondrial fission-related immune markers in abdominal aortic aneurysms.

Purpose: The aim of this study is to investigate abdominal aortic aneurysm (AAA), a disease characterised by inflammation and progressive vasodilatation, for novel gene-targeted therapeutic loci. Methods: To do this, we used weighted co-expression network analysis (WGCNA) and differential gene analysis on samples from the GEO database. Additionally, we carried out enrichment analysis and determined that the blue module was of interest. Additionally, we performed an investigation of immune infiltration and discovered genes linked to immune evasion and mitochondrial fission. In order to screen for feature genes, we used two PPI network gene selection methods and five machine learning methods. This allowed us to identify the most featrue genes (MFGs). The expression of the MFGs in various cell subgroups was then evaluated by analysis of single cell samples from AAA. Additionally, we looked at the expression levels of the MFGs as well as the levels of inflammatory immune-related markers in cellular and animal models of AAA. Finally, we predicted potential drugs that could be targeted for the treatment of AAA. Results: Our research identified 1249 up-regulated differential genes and 3653 down-regulated differential genes. Through WGCNA, we also discovered 44 genes in the blue module. By taking the point where several strategies for gene selection overlap, the MFG (ITGAL and SELL) was produced. We discovered through single cell research that the MFG were specifically expressed in T regulatory cells, NK cells, B lineage, and lymphocytes. In both animal and cellular models of AAA, the MFGs' mRNA levels rose. Conclusion: We searched for the AAA novel targeted gene (ITGAL and SELL), which most likely function through lymphocytes of the B lineage, NK cells, T regulatory cells, and B lineage. This analysis gave AAA a brand-new goal to treat or prevent the disease.

Prenatal Diagnosis of Oral Teratoma by Ultrasound.

A pregnant woman had a normal second-trimester anatomic survey at 22 weeks gestation. She was revealed to have a fetal oral mass with polyhydramnios and invisible stomach bubble by ultrasound at 28 weeks. A 50 mm × 36 mm × 42 mm, solid mass was found in the fetal mouth, filling the entire oral cavity. Fetal magnetic resonance imaging showed a homogeneous solid mass in the oral cavity compressing the hypopharynx. At 33 weeks, preterm labor occurred because of the continuation of increased amniotic fluid volume, and a female infant was vaginally delivered. The infant died shortly after tracheal intubation attempt failed. Autopsy confirmed the prenatal sonographic finding. The final pathologic diagnosis was oral immature teratoma. Our study indicates that although oral teratomas are rare, they are readily apparent at prenatal sonographic examinations. Respiratory compromise is the frequent complication of oral teratomas, which is associated with high perinatal mortality.

Clinical efficacy and kinematic analysis of Chinese knotting technique-assisted posterior cruciate ligament reconstruction: A retrospective analysis.

To investigate the clinical efficacy and knee joint kinematic changes of posterior cruciate ligament (PCL) reconstruction assisted by Chinese knotting technique (CKT). A retrospective analysis was conducted on 88 cases of PCL reconstructive surgery admitted between September 2016 and September 2020. All patients were operated on by the same senior doctor and his team. The patients were divided into 2 groups according to whether the CKT was applied, with 44 cases in each group. Both groups received active rehabilitation treatment after surgery. All patients were followed up for more than 2 years. International knee documentation committee, hospital for special surgery (HSS), and Lysholm scores were used to evaluate the clinical efficacy of the 2 methods at 3, 12, and 24 months after surgery. The motion cycle and kinematic indices of the knee joint were measured by the Opti_Knee three-dimensional motion measurement system before surgery and at 3, 12, and 24 months after surgery. A secondary arthroscopic examination was performed at 12 months after surgery, MAS score was used to evaluate the secondary endoscopic examination of PCL. All the patients had wound healing in stage I without infection. International Knee in both sets Documentation Committee scores, HSS scores and Lysholm scores were gradually improved at all time points (P < .05); compared with the traditional group, the HSS score was higher in the reduction group 12 months after surgery (P < .05), but there was no significant difference at 24 months after surgery. 12 months and 24 months after 3 dimensional motion measurement system using Opti_Knee showed a reduction group before and after displacement and displacement of upper and lower range than the traditional group (P < 0. 05). One year after surgery, the good and good rate of MAS score reduction group was higher than traditional group. CKT assisted PCL reconstruction can improve the subjective function score of the affected knee joint and the results of secondary microscopy. Satisfactory knee kinematic function can be obtained in the early stage, and the anteroposteric relaxation of the knee joint can be reduced.

NRPS-like ATRR in Plant-Parasitic Nematodes Involved in Glycine Betaine Metabolism to Promote Parasitism.

Plant-parasitic nematodes (PPNs) are among the most serious phytopathogens and cause widespread and serious damage in major crops. In this study, using a genome mining method, we identified nonribosomal peptide synthetase (NRPS)-like enzymes in genomes of plant-parasitic nematodes, which are conserved with two consecutive reducing domains at the N-terminus (A-T-R1-R2) and homologous to fungal NRPS-like ATRR. We experimentally investigated the roles of the NRPS-like enzyme (MiATRR) in nematode (Meloidogyne incognita) parasitism. Heterologous expression of Miatrr in Saccharomyces cerevisiae can overcome the growth inhibition caused by high concentrations of glycine betaine. RT-qPCR detection shows that Miatrr is significantly upregulated at the early parasitic life stage (J2s in plants) of M. incognita. Host-derived Miatrr RNA interference (RNAi) in Arabidopsis thaliana can significantly decrease the number of galls and egg masses of M. incognita, as well as retard development and reduce the body size of the nematode. Although exogenous glycine betaine and choline have no obvious impact on the survival of free-living M. incognita J2s (pre-parasitic J2s), they impact the performance of the nematode in planta, especially in Miatrr-RNAi plants. Following application of exogenous glycine betaine and choline in the rhizosphere soil of A. thaliana, the numbers of galls and egg masses were obviously reduced by glycine betaine but increased by choline. Based on the knowledge about the function of fungal NRPS-like ATRR and the roles of glycine betaine in host plants and nematodes, we suggest that MiATRR is involved in nematode-plant interaction by acting as a glycine betaine reductase, converting glycine betaine to choline. This may be a universal strategy in plant-parasitic nematodes utilizing NRPS-like ATRR to promote their parasitism on host plants.

Elucidation of the key therapeutic targets and potential mechanisms of Andrographolide multi-targets against osteoarthritis via network pharmacological analysis and experimental validation.

OBJECTIVE: Our purpose is to unveil Andrographolide's potential multi-target and multi-mechanism therapeutic effects in treating OA via systematic network pharmacological analysis and cell experimental validation. MATERIALS AND METHODS: Initially, we gathered data from Andrographolide and OA-related databases to obtain information on Andrographolide's biological properties and the targets linked with OA. We developed a bioinformatic network about Andrographolide and OA, whereby we analyzed the network to identify potential therapeutic targets and mechanisms of action of Andrographolide. Subsequently, we used molecular docking to analyze the binding sites of Andrographolide to the target proteins. At the same time, SDF-1 was used to construct an OA cell model to verify the therapeutic effect of Andrographolide on OA and its effect on target proteins. RESULTS: Our experimental results show that Andrographolide has excellent pharmaceutical properties, by Lipinski's rules for drugs, suggesting that this compound can be considered to have a high therapeutic potential in drug development. 233 targets were preliminarily investigated, the mechanisms through which Andrographolide targets OA primarily involve the TNF signaling pathway, PI3K-AKT signaling pathway, IL-17 signaling pathway, and TLR signaling pathway. These mechanisms target OA by influencing immune and inflammatory responses in the joints, regulating apoptosis to prevent chondrocyte death. Finally, TNF-α, STAT3, TP53, IL-6, JUN, IL-1ß, HIF-1α, TGF-ß1, and AKT1 were identified as 9 key targets of Andrographolide anti-OA. In addition, our molecular docking analyzes with cell experimental validation further confirm the network pharmacology results. According to our molecular docking results, Andrographolide can bind to all the hub target proteins and has a good binding ability (binding energy < -5 kcal/mol), with the strongest binding affinity to AKT1 of -9.2 kcal/ mol. The results of cell experiments showed that Andrographolide treatment significantly increased the cell viability and the expression of COL2A1 and ACAN proteins. Moreover, 30 µM Andrographolide significantly reversed SDF-1-induced increases in the protein expression of TNF-α, STAT3, TP53, IL-6, JUN, IL-1ß, HIF-1α, and TGF-ß1, and decreases in the protein expression of AKT1. CONCLUSION: This study provides a comprehensive understanding of the potential therapeutic targets and mechanisms of action of Andrographolide in OA treatment. Our findings suggest that Andrographolide is a promising candidate for drug development in the management of OA.

A novel dual polarization multiplexing RoF system integrating optical fiber and FSO channel with AMI downlink signals.

Using dual polarization multiplexing alternate mark inversion (AMI) downlink signals, a novel radio over fiber (RoF) system integrating optical fiber and FSO channel is designed to adapt to applications in mountainous areas and other complex terrain areas. Optical heterodyne technology and self-mixing homodyne detection method are used to realize high sensitivity detection of the received signals after 25.1 km channel (including 1 km single-mode fiber and 100 m free space link) transmission. Moreover, polarization multiplexing technology is introduced to exponentially increase the transmission capacity of downlink signals. This scheme not only can be compatible with traditional optical fiber transmission systems, but also support the wireless optical access application of millimeter wave signals in RoF systems.

Advances in antitumor activity and mechanism of natural steroidal saponins: A review of advances, challenges, and future prospects.

BACKGROUND: Cancer, the second leading cause of death worldwide following cardiovascular diseases, presents a formidable challenge in clinical settings due to the extensive toxic side effects associated with primary chemotherapy drugs employed for cancer treatment. Furthermore, the emergence of drug resistance against specific chemotherapeutic agents has further complicated the situation. Consequently, there exists an urgent imperative to investigate novel anticancer drugs. Steroidal saponins, a class of natural compounds, have demonstrated notable antitumor efficacy. Nonetheless, their translation into clinical applications has remained unrealized thus far. In light of this, we conducted a comprehensive systematic review elucidating the antitumor activity, underlying mechanisms, and inherent limitations of steroidal saponins. Additionally, we propose a series of strategic approaches and recommendations to augment the antitumor potential of steroidal saponin compounds, thereby offering prospective insights for their eventual clinical implementation. PURPOSE: This review summarizes steroidal saponins' antitumor activity, mechanisms, and limitations. METHODS: The data included in this review are sourced from authoritative databases such as PubMed, Web of Science, ScienceDirect, and others. RESULTS: A comprehensive summary of over 40 steroidal saponin compounds with proven antitumor activity, including their applicable tumor types and structural characteristics, has been compiled. These steroidal saponins can be primarily classified into five categories: spirostanol, isospirostanol, furostanol, steroidal alkaloids, and cholestanol. The isospirostanol and cholestanol saponins are found to have more potent antitumor activity. The primary antitumor mechanisms of these saponins include tumor cell apoptosis, autophagy induction, inhibition of tumor migration, overcoming drug resistance, and cell cycle arrest. However, steroidal saponins have limitations, such as higher cytotoxicity and lower bioavailability. Furthermore, strategies to address these drawbacks have been proposed. CONCLUSION: In summary, isospirostanol and cholestanol steroidal saponins demonstrate notable antitumor activity and different structural categories of steroidal saponins exhibit variations in their antitumor signaling pathways. However, the clinical application of steroidal saponins in cancer treatment still faces limitations, and further research and development are necessary to advance their potential in tumor therapy.

Genome-wide transcriptome profiling reveals molecular response pathways of Trichoderma harzianum in response to salt stress.

Trichoderma harzianum exhibits a strong biological control effect on many important plant pathogens, such as Fusarium oxysporum, Botrytis cinerea, and Meloidogyne. However, its biocontrol effectiveness is weakened or reduced under salt stress. The aim of this study was to investigate the molecular response of T. harzianum to salt stress at the whole-genome level. Here, we present a 44.47 Mb near-complete genome assembly of the T. harzianum qt40003 strain for the first time, which was assembled de novo with 7.59 Gb Nanopore sequencing long reads (~170-fold) and 5.2 Gb Illumina short reads (~116-fold). The assembled qt40003 genome contains 12 contigs, with a contig N50 of 4.81 Mb, in which four of the 12 contigs were entirely reconstructed in a single chromosome from telomere to telomere. The qt40003 genome contains 4.27 Mb of repeat sequences and 12,238 protein-coding genes with a BUSCO completeness of 97.5%, indicating the high accuracy and completeness of our gene annotations. Genome-wide transcriptomic analysis was used to investigate gene expression changes related to salt stress in qt40003 at 0, 2% (T2), and 4% (T4) sodium chloride concentrations. A total of 2,937 and 3,527 differentially expressed genes (DEGs) were obtained under T2 and T4 conditions, respectively. GO enrichment analysis showed that the T2-treatment DEGs were highly enriched in detoxification (p < 0.001), while the T4 DEGs were mainly enriched in cell components, mostly in cellular detoxification, cell surface, and cell wall. KEGG metabolic pathway analysis showed that 91 and 173 DEGs were significantly enriched in the T2 and T4 treatments, respectively (p < 0.01), mainly in the glutathione metabolism pathway. We further experimentally analyzed the differentially expressed glutathione transferase genes in the glutathione metabolic pathway, most of which were downregulated (13/15). In addition, we screened 13 genes related to active oxygen clearance, including six upregulated and seven downregulated genes, alongside five fungal hydrophobic proteins, of which two genes were highly expressed. Our study provides high-quality genome information for the use of T. harzianum for biological control and offers significant insights into the molecular responses of T. harzianum under salt-stress conditions.

MOTC: Abdominal Multi-objective Segmentation Model with Parallel Fusion of Global and Local Information.

Convolutional Neural Networks have been widely applied in medical image segmentation. However, the existence of local inductive bias in convolutional operations restricts the modeling of long-term dependencies. The introduction of Transformer enables the modeling of long-term dependencies and partially eliminates the local inductive bias in convolutional operations, thereby improving the accuracy of tasks such as segmentation and classification. Researchers have proposed various hybrid structures combining Transformer and Convolutional Neural Networks. One strategy is to stack Transformer blocks and convolutional blocks to concentrate on eliminating the accumulated local bias of convolutional operations. Another strategy is to nest convolutional blocks and Transformer blocks to eliminate bias within each nested block. However, due to the granularity of bias elimination operations, these two strategies cannot fully exploit the potential of Transformer. In this paper, a parallel hybrid model is proposed for segmentation, which includes a Transformer branch and a Convolutional Neural Network branch in encoder. After parallel feature extraction, inter-layer information fusion and exchange of complementary information are performed between the two branches, simultaneously extracting local and global features while eliminating the local bias generated by convolutional operations within the current layer. A pure convolutional operation is used in decoder to obtain final segmentation results. To validate the impact of the granularity of bias elimination operations on the effectiveness of local bias elimination, the experiments in this paper were conducted on Flare21 dataset and Amos22 dataset. The average Dice coefficient reached 92.65% on Flare21 dataset, and 91.61% on Amos22 dataset, surpassing comparative methods. The experimental results demonstrate that smaller granularity of bias elimination operations leads to better performance.

[Research progress on early postoperative pain management strategies after arthroscopic anterior cruciate ligament reconstruction].

Objective: To summarize the early postoperative pain management strategies for anterior cruciate ligament reconstruction (ACLR), and to select a reasonable and effective pain management plan to promote functional rehabilitation after ACLR. Methods: The literature about the early postoperative pain management strategies of ACLR both domestically and internationally in recent years was extensiverly reviewed, and the effects of improving postoperative pain were reviewed. Results: Currently, physical therapy and oral medication have advantages such as economy and simplicity, but the effect of improving postoperative pain is not satisfactory, often requires a combination of intravenous injection or intravenous pump, which is also a common way to relieve pain. However, in order to meet the analgesic needs of patients, the amount of analgesic drugs used is often large, which increases the incidence of various adverse reactions. Local infiltration analgesia (LIA), including periarticular or intra-articular injection of drugs, can significantly improve the early postoperative pain of ACLR, and achieve similar postoperative effectiveness as nerve block. LIA can be used as an analgesic technique instead of nerve block, and avoid the corresponding weakness of innervated muscles caused by nerve block, which increases the risk of postoperative falls. Many studies have confirmed that LIA can alleviate postoperative early pain in ACLR, especially the analgesic effects of periarticular injection are more satisfactory. It can also avoid the risk of cartilage damage caused by intra-articular injection. However, the postoperative analgesic effect and timeliness still need to be improved. It is possible to consider combining multimodal mixed drug LIA (combined with intra-articular and periarticular) with other pain intervention methods to exert a synergistic effect, in order to avoid the side effects and risks brought by single drugs or single administration route. LIA is expected to become one of the most common methods for relieving postoperative early pain in ACLR. Conclusion: Early pain after arthroscopic ACLR still affects the further functional activities of patients, and all kinds of analgesic methods can achieve certain effectiveness, but there is no unified standard at present, and the advantages and disadvantages of various analgesic methods need further research.

Salt Tolerance in Machilus faberi: Elucidating Growth and Physiological Adaptations to Saline Environments.

Adversity stress is the main environmental factor limiting plant growth and development, including salt and other stress factors. This study delves into the adaptability and salt tolerance mechanisms of Machilus faberi Hemsl, a species with potential for cultivation in salinized areas. We subjected the plants to various salt concentrations to observe their growth responses and to assess key physiological and biochemical indicators. The results revealed that under high salt concentrations (500 and 700 mmol-1/L), symptoms such as leaf yellowing, wilting, and eventual death were observed. Notably, plant height and shoot growth ceased on the 14th day of exposure. Chlorophyll content (a, b, total a + b, and the a/b ratio) initially increased but subsequently decreased under varying levels of salt stress. Similarly, the net photosynthetic rate, stomatal conductance, leaf water content, and root activity significantly declined under these conditions. Moreover, we observed an increase in malondialdehyde levels and relative conductivity, indicative of cellular damage and stress. The activity of superoxide dismutase and ascorbate peroxidase initially increased and then diminished with prolonged stress, whereas peroxidase activity consistently increased. Levels of proline and soluble protein exhibited an upward trend, contrasting with the fluctuating pattern of soluble sugars, which decreased initially but increased subsequently. In conclusion, M. faberi exhibits a degree of tolerance to salt stress, albeit with growth limitations when concentrations exceed 300 mmol-1/L. These results shed light on the plant's mechanisms of responding to salt stress and provide a theoretical foundation for its cultivation and application in salt-affected regions.

Fabrication of Self-Wrinkling Polymer Films with Tunable Patterns through an Interfacial-Fuming-Induced Surface Instability Process.

Inspired by the superglue fuming method for fingerprint collection, this study developed a novel interfacial-fuming-induced surface instability process to generate wrinkled patterns on polymeric substrates. High-electronegativity groups are introduced on the substrate surface to initiate the polymerization of monomer vapors, such as ethyl cyanoacrylate, which results in the formation of a stiff poly(ethyl cyanoacrylate) capping layer. Moreover, interfacial polymerization resulted in the covalent bonding of the substrate, which led to the volumetric shrinkage of the composite and the accumulation of compressive strain. This process ultimately resulted in the development and stabilization of wrinkled surface morphologies. The authors systematically examined parameters such as the modulus of the epoxy substrate, prestrain, the flow rate of fuming, and operating temperature. The aforementioned technique can be easily applied to architectures with complex outer morphologies and inner surfaces, thereby enabling the construction of surface patterns under ambient conditions without vacuum limitations or precise process control. This study is the first to combine fuming-induced interfacial polymerization with surface instability to create robust wrinkles. The proposed method enables the fabrication of intricate microwrinkled patterns and has considerable potential for use in various practical applications, including microfluidics, optical components, bioinspired adhesive devices, and interfacial engineering.