The safety and efficacy of neoadjuvant PD-1 inhibitor plus chemotherapy for patients with locally advanced gastric cancer: A systematic review and meta-analysis.

BACKGROUND: The extensive utilization of immune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1 (PD-1) has achieved significant advancements in the treatment of diverse solid tumors. The present meta-analysis aims to evaluate the safety and efficacy of neoadjuvant chemotherapy (NCT) plus PD-1 inhibitor for patients with locally advanced gastric cancer (LAGC). METHODS: An electronic search of PubMed, EmBase, and the Cochrane Library was performed to identify the clinical trials of NCT + PD-1 inhibitor vs. NCT in patients with LAGC. The retrieval period extended from the establishment of the corresponding database until April 2024, and meta-analysis was conducted using Stata (version 15) software. Subsequently, direct comparative analysis was used to compare pooled results of neoadjuvant immunochemotherapy (NICT) with NCT. RESULTS: After screening, 6 phase II/III randomized controlled trials (RCTs) and 9 retrospective studies with 2,953 patients were included. In meta-analysis, NICT group demonstrated a significantly higher rate of pathological complete response (pCR) (P<0.001) and R0 resection (P=0.001), and a lower 2-year recurrence rate (P=0.001) compared to the NCT group. The NICT group, however, exhibited a higher incidence of severe treatment-related adverse events (TRAEs) (P=0.044). Additionally, the NICT and NCT groups exhibited no statistical differences in terms of the number of harvested lymph nodes, the occurrence of total TRAEs and postoperative complications, as well as the duration of postoperative hospitalization. CONCLUSIONS: The combination of PD-1 inhibitor + NCT in LAGC patients enhances the likelihood of achieving radical surgery and improves prognosis, albeit to some extent increasing the risk of severe TRAEs. NICT is anticipated to emerge as the preferred neoadjuvant therapy option for patients diagnosed with LAGC.

A Cooperative Intrusion Detection System for the Internet of Things Using Convolutional Neural Networks and Black Hole Optimization.

Maintaining security in communication networks has long been a major concern. This issue has become increasingly crucial due to the emergence of new communication architectures like the Internet of Things (IoT) and the advancement and complexity of infiltration techniques. For usage in networks based on the Internet of Things, previous intrusion detection systems (IDSs), which often use a centralized design to identify threats, are now ineffective. For the resolution of these issues, this study presents a novel and cooperative approach to IoT intrusion detection that may be useful in resolving certain current security issues. The suggested approach chooses the most important attributes that best describe the communication between objects by using Black Hole Optimization (BHO). Additionally, a novel method for describing the network's matrix-based communication properties is put forward. The inputs of the suggested intrusion detection model consist of these two feature sets. The suggested technique splits the network into a number of subnets using the software-defined network (SDN). Monitoring of each subnet is done by a controller node, which uses a parallel combination of convolutional neural networks (PCNN) to determine the presence of security threats in the traffic passing through its subnet. The proposed method also uses the majority voting approach for the cooperation of controller nodes in order to more accurately detect attacks. The findings demonstrate that, in comparison to the prior approaches, the suggested cooperative strategy can detect assaults in the NSLKDD and NSW-NB15 datasets with an accuracy of 99.89 and 97.72 percent, respectively. This is a minimum 0.6 percent improvement.

Divergent molecular strategies drive evolutionary adaptation to competitive fitness in biofilm formation.

Biofilm is a group of heterogeneously structured and densely packed bacteria with limited access to nutrients and oxygen. These intrinsic features can allow a mono-species biofilm to diversify into polymorphic subpopulations, determining the overall community's adaptive capability to changing ecological niches. However, the specific biological functions underlying biofilm diversification and fitness adaptation are poorly demonstrated. Here, we launched and monitored the experimental evolution of Pseudomonas aeruginosa biofilms, finding that two divergent molecular trajectories were adopted for adaptation to higher competitive fitness in biofilm formation: one involved hijacking bacteriophage superinfection to aggressively inhibit kin competitors, whereas the other induced a subtle change in cyclic dimeric guanosine monophosphate signaling to gain a positional advantage via enhanced early biofilm adhesion. Bioinformatics analyses implicated that similar evolutionary strategies were prevalent among clinical P. aeruginosa strains, indicative of parallelism between natural and experimental evolution. Divergence in the molecular bases illustrated the adaptive values of genomic plasticity for gaining competitive fitness in biofilm formation. Finally, we demonstrated that these fitness-adaptive mutations reduced bacterial virulence. Our findings revealed how the mutations intrinsically generated from the biofilm environment influence the evolution of P. aeruginosa.

Loratadine Derivative Lo-7: A Weapon against Drug-Resistant Enterococcus and Streptococcal Infections.

The primary obstacles in the management of Enterococcus and Streptococcal infections are drug resistance and biofilm formation. Our study revealed that loratadine at a concentration of ≥25 µM exhibited significant inhibitory effects on biofilm formation in 167 clinical strains of Enterococcus faecalis and 15 clinical isolates of Streptococcus agalactiae, Streptococcus pyogenes, and Streptococcus pneumoniae. Additionally, the antibiofilm activity against E. faecalis and Streptococcal was demonstrated by several loratadine derivatives with altered side-chain carbamate moieties. This study investigated the antibacterial activity of the loratadine derivative Lo-7 against clinical strains of S. agalactiae and S. pyogenes, with minimum inhibitory concentrations ranging from 12.5 to 25 µM. The findings revealed that a low concentration of loratadine derivative Lo-7 (3.125 µM) significantly augmented the bactericidal efficacy of vancomycin against multidrug-resistant (MDR) S. agalactiae, both in vitro and in vivo. The loratadine derivative Lo-7, even at low concentrations, demonstrated significant efficacy in eliminating intracellular MDR S. agalactiae within macrophages, potentially indicating a unique advantage over vancomycin, linezolid, and loratadine. Mechanistically, exposure to the loratadine derivative Lo-7 resulted in membrane depolarization without affecting membrane permeability in S. agalactiae. The potential targeting of the SecG subunit of the SecYEG membrane-embedded channel by the loratadine derivative Lo-7 in S. agalactiae was identified through quantitative proteomics, a drug affinity responsive target stability assay, and molecular docking.

Identification of key biomarkers for early warning of diabetic retinopathy using BP neural network algorithm and hierarchical clustering analysis.

Diabetic retinopathy is one of the most common microangiopathy in diabetes, essentially caused by abnormal blood glucose metabolism resulting from insufficient insulin secretion or reduced insulin activity. Epidemiological survey results show that about one third of diabetes patients have signs of diabetic retinopathy, and another third may suffer from serious retinopathy that threatens vision. However, the pathogenesis of diabetic retinopathy is still unclear, and there is no systematic method to detect the onset of the disease and effectively predict its occurrence. In this study, we used medical detection data from diabetic retinopathy patients to determine key biomarkers that induce disease onset through back propagation neural network algorithm and hierarchical clustering analysis, ultimately obtaining early warning signals of the disease. The key markers that induce diabetic retinopathy have been detected, which can also be used to explore the induction mechanism of disease occurrence and deliver strong warning signal before disease occurrence. We found that multiple clinical indicators that form key markers, such as glycated hemoglobin, serum uric acid, alanine aminotransferase are closely related to the occurrence of the disease. They respectively induced disease from the aspects of the individual lipid metabolism, cell oxidation reduction, bone metabolism and bone resorption and cell function of blood coagulation. The key markers that induce diabetic retinopathy complications do not act independently, but form a complete module to coordinate and work together before the onset of the disease, and transmit a strong warning signal. The key markers detected by this algorithm are more sensitive and effective in the early warning of disease. Hence, a new method related to key markers is proposed for the study of diabetic microvascular lesions. In clinical prediction and diagnosis, doctors can use key markers to give early warning of individual diseases and make early intervention.

Presence of compensatory curve predicts postoperative curve progression in congenital scoliosis after thoracolumbar hemivertebra resection and short fusion.

PURPOSE: To investigate the impact of preoperative compensatory curve on the postoperative curve progression in congenital scoliosis (CS) patients following thoracolumbar hemivertebra (HV) resection and short fusion. METHODS: This study retrospectively reviewed a consecutive cohort of patients with CS who underwent thoracolumbar HV resection and short fusion with a minimum of 2 years follow-up. According to the preoperative curve pattern, patients were divided into compensatory curve group non-compensatory curve group. Based on the postoperative coronal curve evolution, patients were further divided into the progressed group (Group P, with curve decompensation ≥ 20°) and the non-progressed group (Group NP, characterized by well-compensated curves). RESULTS: A total of 127 patients were included in this study, with 31 patients in the compensatory curve group and 96 patients in the non-compensatory curve group. The incidence of postoperative coronal curve progression was significantly higher in the compensatory curve group than that in non-compensatory curve group (35.5% vs. 13.5%, p = 0.007). In the compensatory curve group, patients who experienced postoperative curve progression showed fewer fusion segments (p = 0.001), greater preoperative UIV translation (p = 0.006), greater preoperative LIV tilt (p = 0.017), and larger postoperative UIV tilt (p < 0.001) compared with patients in group NP. Multiple logistic regression demonstrated that the shorter fusion segments and greater postoperative UIV tilt were two independent risk factors for postoperative curve progression. CONCLUSION: The presence of the compensatory curve was associated with a higher incidence of postoperative curve progression in patients with CS who underwent thoracolumbar HV resection and short fusion. Shorter fusion segments and greater postoperative UIV tilt were found to be the risk factors for postoperative curve progression.

Antibacterial Activity and Mechanism of Candesartan Cilexetil against Enterococcus faecalis.

Enterococcus faecalis infections pose a significant clinical challenge due to their multidrug resistance and propensity for biofilm formation. Exploring alternative treatment options, such as repurposing existing drugs, is crucial in addressing this issue. This study investigates the antibacterial activity of candesartan cilexetil against E. faecalis and elucidates its mechanism of action. Candesartan cilexetil exhibited notable antibacterial activity against both E. faecalis and Enterococcus faecium, with minimum inhibitory concentration (MIC) of ≤25 µM. Time-kill curves demonstrated concentration-dependent bactericidal effects. Candesartan cilexetil could significantly inhibited biofilm formation at the concentration of 1/4× MIC and induced alterations in biofilm structure. Permeability assays revealed compromised bacterial membranes, accompanied by the dissipation of membrane potential in E. faecalis cells after treatment with candesartan cilexetil. Checkerboard analysis showed that bacterial membrane phospholipids phosphatidylglycerol and cardiolipin could neutralize the antibacterial activity of candesartan cilexetil in a dose-dependent manner. Biolayer interferometry (BLI) assay indicated specific interactions between candesartan cilexetil and phosphatidylglycerol or cardiolipin. This study demonstrates the promising antibacterial and antibiofilm activities of candesartan cilexetil against multidrug-resistant E. faecalis. The mechanism of action involves disruption of bacterial membranes, possibly by interacting with membrane phospholipids. These findings underscore the potential utility of candesartan cilexetil as an effective therapeutic agent for combating E. faecalis infections, offering a valuable strategy in the battle against antibiotic-resistant pathogens.

Fluidized Reduction Kinetics of Boron-Bearing Iron Concentrate by Hydrogen at Low Temperatures Based on Model-Fitting and Model-Free Methods.

Pyrometallurgy is the most effective way to comprehensively utilize boron-bearing iron concentrate, and there is an urgency for an environmentally friendly and efficient method to achieve the prereduction of boron-bearing iron concentrate. In this study, the mechanism and kinetics of isothermal hydrogen reduction of boron-bearing iron concentrate in a fluidized bed at 500-570 °C were discussed. The reduction degree was quantified in combination with the online gas composition analysis technique, and the phase and microstructure of the reduced products were characterized. The results exhibited that the apparent activation energy remained constant during the whole reduction process, with average values of 50.67 and 48.08 kJ/mol calculated by the model-free and model-fitting methods, respectively, and the reaction was controlled by the contracting sphere model. The formation of a microporous metallic iron facilitated the rapid penetration of hydrogen to the reaction interface. Therefore, the intrinsic chemical reaction at the interface determined the whole reaction process.

Reprogrammable, Sustainable, and 3D-Printable Cellulose Hydroplastic.

Modern human societies are highly dependent on plastic materials, however, the bulk of them are non-renewable commodity plastics that cause pollution problems and consume large amounts of energy for their thermal processing activities. In this article, a sustainable cellulose hydroplastic material and its composites, that can be shaped repeatedly into various 2D/3D geometries using just water are introduced. In the wet state, their high flexibility and ductility make it conducive for the shaping to take place. In the ambient environment, the wet hydroplastic transits spontaneously into rigid materials with its intended shape in a short time of <30 min despite a thickness of hundreds of microns. They also possess humidity resistance and are structurally stable in highly humid environments. Given their excellent mechanical properties, geometry reprogrammability, bio-based, and biodegradable nature, cellulose hydroplastic poses as a sustainable alternative to traditional plastic materials and even "green" thermoplastics. This article also demonstrates the possibility of 3D-printing these hydroplastics and the potential of employing them in electronics applications. The demonstrated hydroshapable structural electronic components show capability in performing electronic functions, load-bearing ability and geometry versatility, which are attractive features for lightweight, customizable and geometry-unique electronic devices.

Clinicopathologic factors correlated with lymph node metastasis in gastric cancer: a retrospective cohort study involving 5606 patients.

BACKGROUND: The identification of risk factors associated with lymph node metastasis (LNM) in gastric cancer will establish a crucial foundation for the implementation of endoscopic operation and multidisciplinary treatment programs. METHODS: A total of 5606 patients with gastric cancer with comprehensive clinicopathologic data were enrolled through systematic searching and rigorous screening. Of the 5606 patients, 1438 were diagnosed with early gastric cancer (EGC), which would be used for further analysis. Subsequently, univariate and multivariate logistic regression analyses were performed to identify the risk factors. RESULTS: The rates of LNM in T1a, T1b, T2, T3, T4a, and T4b stage gastric cancer were 7.0%, 19.4%, 48.4%, 77.1%, 83.8%, and 89.6%, respectively. Female (odds ratio [OR], 1.559; P = .032), lower tumor location (OR, 1.773; P = .023), tumor size of >2 cm (OR, 2.007; P < .001), mixed (OR, 2.371; P = .001) and undifferentiated histologic types (OR, 2.952; P < .001), T1b stage (OR, 2.041; P < .001), presence of ulceration (OR, 1.758; P = .027), and lymphovascular invasion (OR, 5.722; P < .001) were identified as independent risk factors for LNM in EGC. A nomogram was constructed using appropriate predictors to preoperatively predict the risk of LNM in patients with EGC. CONCLUSION: This study identified the clinicopathologic factors associated with LNM in patients with EGC and developed a prediction model, thereby facilitating the integration of diverse treatment modalities in managing patients with EGC.

Baohuoside I inhibits virulence of multidrug-resistant Staphylococcus aureus by targeting the transcription Staphylococcus accessory regulator factor SarZ.

BACKGROUND: Staphylococcus aureus is a versatile pathogen that can cause a wide range of infections in humans. Biofilms play a crucial role in the pathogenicity of S. aureus and contribute to its ability to cause persistent and chronic infections. Baohuoside I has garnered increasing recognition as a natural flavonol glycoside with a wide spectrum of health-related activities. PURPOSE: The antibacterial and anti-biofilm properties of Baohuoside I have not been extensively investigated. Our study aimed to assess its inhibitory effects and the underlying mechanisms on biofilm formation and hemolytic capacity in S. aureus. STUDY DESIGN/METHODS: The impact of Baohuoside I on the biofilm and virulence of S. aureus was evaluated through in vitro experiments and Galleria mellonella as an in vivo infection model. The mechanisms were explored by Drug affinity responsive target stability (DARTS) and validated in genetic knockout strain and through molecular biological experiments using DARTS, molecular docking, electrophoretic mobility shift assay (EMSA), and bio-layer interferometry (BLI). RESULTS: Baohuoside I significantly inhibits the formation of S. aureus biofilms and hemolytic activity at 6.25 µM. Proteomics analysis revealed that treatment with Baohuoside I led to a reduction in the expression of quorum-sensing system agr-regulated genes. DARTS analysis identified Staphylococcus accessory regulator factor (SarZ), a key regulator involved in the expression of virulence factors in S. aureus by acting as activator of the agr quorum-sensing system, was the direct target of Baohuoside I. Molecular docking, DARTS, BLI and EMSA assays collectively confirmed the direct binding of Baohuoside I to SarZ, inhibiting its binding to downstream promoters. Furthermore, it is found through site-directed protein mutagenesis that the Tyr27 and Phe117 residues are key for Baohuoside I binding to SarZ. Additionally, the knockout of SarZ significantly diminished the hemolytic ability of S. aureus, underscoring its crucial role as a pivotal regulator of virulence. Lastly, in vivo tests utilizing the G. mellonella infection model demonstrated the efficacy of Baohuoside I. CONCLUSION: This study provides valuable insights into the mechanism by which Baohuoside I inhibits the virulence of S. aureus through its interaction with SarZ. These findings highlight the significance of SarZ as an effective target against the virulence of S. aureus.

Hi-C, a chromatin 3D structure technique advancing the functional genomics of immune cells.

The functional performance of immune cells relies on a complex transcriptional regulatory network. The three-dimensional structure of chromatin can affect chromatin status and gene expression patterns, and plays an important regulatory role in gene transcription. Currently available techniques for studying chromatin spatial structure include chromatin conformation capture techniques and their derivatives, chromatin accessibility sequencing techniques, and others. Additionally, the recently emerged deep learning technology can be utilized as a tool to enhance the analysis of data. In this review, we elucidate the definition and significance of the three-dimensional chromatin structure, summarize the technologies available for studying it, and describe the research progress on the chromatin spatial structure of dendritic cells, macrophages, T cells, B cells, and neutrophils.

Risk factors associated with lymph node metastasis in early-stage distal gastric cancer.

OBJECTS: This study was designed to explore the risk factors of lymph node metastasis (LNM) in distal gastric cancer with early stage, and to provide reference for the choice of treatment protocols. METHODS: In this retrospective observational study, 824 early distal gastric cancer (EDGC) cases who treated at our unit from 2010 to 2020 were selected as research objects. Subsequently, univariate and multivariate logistic regression analyses were conducted to investigate the associations between LNM and clinicopathological features. RESULTS: Of these 824 EDGC cases, 140 (17.0%) developed LNM, including 72 N1 stage and 68 N2-3 stage LNM. Multivariate logistic regression analysis identified the tumor diameter ≥1.75 cm (odds ratio (OR) = 2.361, p < 0.001), tumor location (OR = 1.552, p = 0.046), histological classification (p = 0.004), tumor infiltration depth (OR = 2.154, p = 0.001), and vascular infiltration (OR = 4.354, p < 0.001) as independent predictors for LNM. Logistic regression analyses based on 756 N0-1 LNM cases identified the smoking history (OR = 0.507, p = 0.043), tumor diameter ≥1.75 cm (OR = 2.265, p = 0.010), tumor location (OR = 1.834, p = 0.036), histological classification (p = 0.018), tumor infiltration depth (OR = 1.939, p = 0.034), and vascular infiltration (OR = 3.225, p < 0.001) as independent predictors for N1 LNM. Moreover, preoperative hypoalbuminemia (OR = 7.087, p = 0.015), significant preoperative weight loss (OR = 2.724, p = 0.023), tumor diameter ≥1.75 cm (OR = 5.484, p = 0.001), multiple tumors (OR = 9.986, p = 0.038), histological classification (p = 0.029), and vascular infiltration (OR = 33.704, p < 0.001) were proved to be associated with LNM for T1a tumors. CONCLUSIONS: The tumor diameter, location and infiltration depth, histological classification, and vascular infiltration were expected to be used as predictors of LNM in EDGC, and preoperative hypoalbuminemia, significant weight loss, tumor diameter and number, histological classification, and vascular infiltration were associated with LNM for T1a tumors.

Deciphering the population structure and genetic basis of growth traits from whole-genome resequencing of the leopard coral grouper ( Plectropomus leopardus).

The leopard coral grouper ( Plectropomus leopardus) is a species of significant economic importance. Although artificial cultivation of P. leopardus has thrived in recent decades, the advancement of selective breeding has been hindered by the lack of comprehensive population genomic data. In this study, we identified over 8.73 million single nucleotide polymorphisms (SNPs) through whole-genome resequencing of 326 individuals spanning six distinct groups. Furthermore, we categorized 226 individuals with high-coverage sequencing depth (≥14×) into eight clusters based on their genetic profiles and phylogenetic relationships. Notably, four of these clusters exhibited pronounced genetic differentiation compared with the other populations. To identify potentially advantageous loci for P. leopardus, we examined genomic regions exhibiting selective sweeps by analyzing the nucleotide diversity ( θπ) and fixation index ( F ST) in these four clusters. Using these high-coverage resequencing data, we successfully constructed the first haplotype reference panel specific to P. leopardus. This achievement holds promise for enabling high-quality, cost-effective imputation methods. Additionally, we combined low-coverage sequencing data with imputation techniques for a genome-wide association study, aiming to identify candidate SNP loci and genes associated with growth traits. A significant concentration of these genes was observed on chromosome 17, which is primarily involved in skeletal muscle and embryonic development and cell proliferation. Notably, our detailed investigation of growth-related SNPs across the eight clusters revealed that cluster 5 harbored the most promising candidate SNPs, showing potential for genetic selective breeding efforts. These findings provide a robust toolkit and valuable insights into the management of germplasm resources and genome-driven breeding initiatives targeting P. leopardus.

Does business environment optimization improve carbon emission efficiency? Evidence from provincial panel data in China.

Previous research has yielded mixed conclusions regarding whether business environment (BE) optimization can enhance carbon emission efficiency (CEE). This study delves into the impact of the BE on CEE using panel data from 30 provinces in China, employing fixed effect, quantile, and mediated effect models. It innovates in three key areas: research perspective, mechanism of action, and heterogeneity analysis. The research found that the BE optimization enhances CEE. Meanwhile, the influence of the BE on CEE exhibits marginal decreasing characteristics. The mechanism analysis reveals that the BE enhances CEE through the industrial structure optimization effect and the progress of green technology, while it diminishes efficiency through the energy rebound effect. Heterogeneity analysis indicates that BE optimization has a stronger impact on improving CEE in provinces with robust government governance, younger governors, and highly educated officials. The policy implication suggests that local governments should continually optimize the BE, enhance government governance capacity, and prioritize the appointment of young and highly educated officials.

Irreversible Transmural Intestinal Necrosis in Acute Mesenteric Ischemia: Retrospective Cohort Study from a High-Volume Hospital.

Background: Owing to the low incidence rate and nonspecific symptoms of acute mesenteric ischemia (AMI), the identification and prediction of irreversible transmural intestinal necrosis (ITIN) and extensive bowel resection (≥100 cm) (EBR) are difficult and critical. This study aimed to investigate the risk factors for ITIN and EBR in patients with AMI. Methods: The clinical data of 254 AMI patients were retrospectively analyzed. Furthermore, the incidence of ITIN and EBR were set as dependent variables, and relevant risk factors were screened using univariate and multivariate logistic regression analyses. The comparisons of surgical characteristics and postoperative recovery outcomes between the EBR and control group were also conducted. Results: The presence of hemorrhagic (odds ratio [OR] = 28.356, P < .001) or other types ascites (OR = 13.051, P = .003), peritonitis (OR = 8.463, P = .005), intestinal diameter >2.35 cm (OR = 5.493, P = .020), and serum creatinine (CREA) >95 µmol/L (OR = 4.866, P = .048) were identified as independent risk factors for ITIN in patients with AMI. In addition, serum C-reactive protein (CRP) >15 mg/L (OR = 38.023, P = .006), and CREA >100 µmol/L (OR = 6.248, P = .035) were proved to be independently associated with EBR for ITIN cases. Compared to the control group, EBR significantly increased the likelihood of requiring enterostomy (P = .001), blood transfusion (P = .002), and transfer to intensive care unit (P = .016), while also prolonging the recovery time for intestinal function (P = .014). Conclusions: The presence of ascites, peritonitis, intestinal diameter >2.35 cm, and serum CREA >95 µmol/L were independently correlated with ITIN for AMI cases, while serum CRP >15 mg/L and CREA >100 µmol/L independently increased the risk of EBR.

Theoretical Analysis and Expression Profiling of 17ß-Hydroxysteroid Dehydrogenase Genes in Gonadal Development and Steroidogenesis of Leopard Coral Grouper (Plectropomus leopardus).

The differentiation and developmental trajectory of fish gonads, significantly important for fish breeding, culture, and production, has long been a focal point in the fields of fish genetics and developmental biology. However, the mechanism of gonadal differentiation in leopard coral grouper (Plectropomus leopardus) remains unclear. This study investigates the 17ß-Hydroxysteroid Dehydrogenase (Hsd17b) gene family in P. leopardus, with a focus on gene characterization, expression profiling, and functional analysis. The results reveal that the P. leopardus's Hsd17b gene family comprises 11 members, all belonging to the SDR superfamily. The amino acid similarity is only 12.96%, but conserved motifs, such as TGxxxGxG and S-Y-K, are present in these genes. Hsd17b12a and Hsd17b12b are unique homologs in fish, and chromosomal localization has confirmed that they are not derived from different transcripts of the same gene, but rather are two independent genes. The Hsd17b family genes, predominantly expressed in the liver, heart, gills, kidneys, and gonads, are involved in synthesizing or metabolizing sex steroid hormones and neurotransmitters, with their expression patterns during gonadal development categorized into three distinct categories. Notably, Hsd17b4 and Hsd17b12a were highly expressed in the testis and ovary, respectively, suggesting their involvement in the development of reproductive cells in these organs. Fluorescence in situ hybridization (FISH) further indicated specific expression sites for these genes, with Hsd17b4 primarily expressed in germ stem cells and Hsd17b12a in oocytes. This comprehensive study provides foundational insights into the role of the Hsd17b gene family in gonadal development and steroidogenesis in P. leopardus, contributing to the broader understanding of fish reproductive biology and aquaculture breeding.

Identification of predictors for short-term recurrence: comprehensive analysis of 296 retroperitoneal liposarcoma cases.

BACKGROUND: The short-term (≤ 1 year) recurrence (STR) is the primary determinant impacting both the life quality and survival duration in patients who have undergone surgical resection for retroperitoneal liposarcoma (RPLS), a condition with intricate and ambiguous pathogenesis. The purpose of this study was to analyze the risk factors associated with STR in cases of RPLS and primary retroperitoneal liposarcoma (PRPLS). METHODS: For this retrospective observational study, a total of 296 RPLS cases were selected as research subjects, who experienced tumor recurrence during the follow-up period. The Local recurrence-free survival (LRFS) rates were estimated using the Kaplan-Meier method and subsequently compared between groups utilizing the log-rank test. The subsequent analyses involved univariate and multivariate logistic regression to identify predictors of STR in RPLS cases. Additionally, a logistic regression model was constructed for PRPLS. RESULTS: The 1-, 3-, and 5-year LRFS rates of the 296 RPLS cases were 51.7%, 16.9%, and 7.1%, respectively. In the univariate analysis, several factors were found to be associated with STR, including preoperative neutrophil/lymphocyte ratio (NLR), smoking history, surgical frequency, combined organ excision, operative time, intraoperative bleeding, transfer to the intensive care unit (ICU), multiple primary tumors, tumor shape and capsule characteristics, histological subtype, and presence of tumor necrosis. The elevated preoperative NLR, surgical frequency of ≥ 3 times, transfer to the ICU, presence of multiple primary tumors, and tumor necrosis were identified as independent risk factors for STR in surgically resected RPLS. Conversely, diabetes, intact tumor capsule, and well-differentiated histological subtype appeared to be independent protective factors. Analysis for PRPLS revealed that tumor capsule and tumor necrosis were independent predictors of STR. CONCLUSIONS: The elevated preoperative NLR, surgical frequency of ≥ 3 times, transfer to the ICU, presence of multiple primary tumors, tumor necrosis, and tumor capsule were expected to serve as predictive factors of STR for surgical resected RPLS and PRPLS.

Surgical outcomes after reoperation for patients with recurrent presacral tumors: a retrospective study.

BACKGROUND: Relevant reports on the surgical resection and prognosis of recurrent presacral tumors are limited. The objective of this study was to explore the outcomes associated with surgical resection of recurrent presacral tumors. METHODS: The data of patients with recurrent presacral tumors who received surgical resection in our hospital between June 2009 and November 2018 were retrospectively analyzed. RESULTS: Thirty-one patients, comprising 22 females and 9 males, with recurrent presacral lesions were included in our study. A posterior approach was utilized in 27 patients, an anterior approach in 1 patient, and a combined approach in 3 patients. Intraoperative complications occurred in 13 patients (41.9%), while postoperative complications occurred in 6 patients (19.4%). The length of hospital stay was significantly shorter in patients who underwent the posterior approach compared to those who underwent the anterior and combined approaches (P = 0.002). The operative time for the posterior approach was significantly shorter compared to both the anterior and combined approaches (P = 0.006). Temporary tamponade was performed for hemostasis in 4 patients, while staged resection was performed in 2 patients during the surgical treatment process. After a median follow-up period of 115.5 months, 5 patients with recurrent malignant presacral tumors succumbed to tumor recurrence after reoperation in our hospital. CONCLUSIONS: Surgical resection remains the mainstream treatment for recurrent presacral tumors. The outcomes for recurrent benign presacral tumors after surgery demonstrate favorable results, whereas further enhancements are required to improve the outcomes for recurrent malignant presacral tumors after surgery.

Impacts of small-molecule STAT3 inhibitor SC-43 on toxicity, global proteomics and metabolomics of HepG2 cells.

OBJECTIVE: In this study, we aimed to investigate the cytotoxicity and potential mechanisms of SC-43 by analyzing the global proteomics and metabolomics of HepG2 cells exposed to SC-43. METHODS: The effect of SC-43 on cell viability was evaluated through CCK-8 assay. Proteomics and metabolomics studies were performed on HepG2 cells exposed to SC-43, and the functions of differentially expressed proteins and metabolites were categorized. Drug affinity responsive target stability (DARTS) was utilized to identify the potential binding proteins of SC-43 in HepG2 cells. Finally, based on the KEGG pathway database, the co-regulatory mechanism of SC-43 on HepG2 cells was elucidated by conducting a joint pathway analysis on the differentially expressed proteins and metabolites using the MetaboAnalyst 5.0 platform. RESULTS: Liver cell viability is significantly impaired by continuous exposure to high concentrations of SC-43. Forty-eight dysregulated proteins (27 upregulated, 21 downregulated) were identified by proteomics analysis, and 184 dysregulated metabolites (65 upregulated, 119 downregulated) were determined by metabolomics in HepG2 cells exposed to SC-43 exposure compared with the control. A joint pathway analysis of proteomics and metabolomics data using the MetaboAnalyst 5.0 platform supported the close correlation between SC-43 toxicity toward HepG2 and the disturbances in pyrimidine metabolism, ferroptosis, mismatch repair, and ABC transporters. Specifically, SC-43 significantly affected the expression of several proteins and metabolites correlated with the above-mentioned functional pathways, such as uridine 5'-monophosphate, uridine, 3'-CMP, glutathione, γ-Glutamylcysteine, TF, MSH2, RPA1, RFC3, TAP1, and glycerol. The differential proteins suggested by the joint analysis were further selected for ELISA validation. The data showed that the RPA1 and TAP1 protein levels significantly increased in HepG2 cells exposed to SC-43 compared to the control group. The results of ELISA and joint analysis were basically in agreement. Notably, DARTS and biochemical analysis indicated that SART3 might be a potential target for SC-43 toxicity in HepG2 cells. CONCLUSION: In summary, prolonged exposure of liver cells to high concentrations of SC-43 can result in significant damage. Based on a multi-omics analysis, we identified proteins and metabolites associated with SC-43-induced hepatocellular injury and clarified the underlying mechanism, providing new insights into the toxic mechanism of SC-43.