Capecitabine or Capecitabine Plus Oxaliplatin Versus Fluorouracil Plus Cisplatin in Definitive Concurrent Chemoradiotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma (CRTCOESC): A Multicenter, Randomized, Open-Label, Phase 3 Trial.

PURPOSE: This phase 3 trial aimed to compare the efficacy and safety of capecitabine or capecitabine plus oxaliplatin (XELOX) with those of fluorouracil plus cisplatin (PF) in definitive concurrent chemoradiotherapy (DCRT) for inoperable locally advanced esophageal squamous cell carcinoma (ESCC). METHODS: Patients were randomly assigned to receive two cycles of capecitabine, XELOX, or PF along with concurrent intensity-modulated radiation therapy. Patients in each arm were again randomly assigned to receive two cycles of consolidation chemotherapy or not. The primary end points were 2-year overall survival (OS) rate and incidence of grade ≥3 adverse events (AEs). RESULTS: A total of 246 patients were randomly assigned into the capecitabine (n = 80), XELOX (n = 85), and PF (n = 81) arms. In capecitabine, XELOX, and PF arms, the 2-year OS rate was 75%, 66.7%, and 70.9% (capecitabine v PF: hazard ratio [HR], 0.91 [95% CI, 0.61 to 1.35]; nominal P = .637; XELOX v PF: 0.86 [95% CI, 0.58 to 1.27]; P = .444); the median OS was 40.9 (95% CI, 34.4 to 49.9), 41.9 (95% CI, 28.6 to 52.1), and 35.4 (95% CI, 30.4 to 45.4) months. The incidence of grade ≥3 AEs during the entire treatment was 28.8%, 36.5%, and 45.7%, respectively. Comparing the consolidation chemotherapy with the nonconsolidation chemotherapy groups, the median OS was 41.9 (95% CI, 34.6 to 52.8) versus 36.9 (95% CI, 28.5 to 44) months (HR, 0.71 [95% CI, 0.52 to 0.99]; nominal P = .0403). CONCLUSION: Capecitabine or XELOX did not significantly improve the 2-year OS rate over PF in DCRT for inoperable locally advanced ESCC. Capecitabine showed a lower incidence of grade ≥3 AEs than PF did.

Tumor cell-intrinsic epigenetic dysregulation shapes cancer-associated fibroblasts heterogeneity to metabolically support pancreatic cancer.

The tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDAC) involves a significant accumulation of cancer-associated fibroblasts (CAFs) as part of the host response to tumor cells. The origins and functions of transcriptionally diverse CAF populations in PDAC remain poorly understood. Tumor cell-intrinsic genetic mutations and epigenetic dysregulation may reshape the TME; however, their impacts on CAF heterogeneity remain elusive. SETD2, a histone H3K36 trimethyl-transferase, functions as a tumor suppressor. Through single-cell RNA sequencing, we identify a lipid-laden CAF subpopulation marked by ABCA8a in Setd2-deficient pancreatic tumors. Our findings reveal that tumor-intrinsic SETD2 loss unleashes BMP2 signaling via ectopic gain of H3K27Ac, leading to CAFs differentiation toward lipid-rich phenotype. Lipid-laden CAFs then enhance tumor progression by providing lipids for mitochondrial oxidative phosphorylation via ABCA8a transporter. Together, our study links CAF heterogeneity to epigenetic dysregulation in tumor cells, highlighting a previously unappreciated metabolic interaction between CAFs and pancreatic tumor cells.

Synthesis of BiOX-Red Mud/Granulated Blast Furnace Slag Geopolymer Microspheres for Photocatalytic Degradation of Formaldehyde.

Release of formaldehyde gas indoors is a serious threat to human health. The traditional adsorption method is not stable enough for formaldehyde removal. Photocatalytic degradation of formaldehyde is effective and rapid, but photocatalysts are generally expensive and not easy to recycle. In this paper, geopolymer microspheres were applied as matrix materials for photocatalysts loading to degrade formaldehyde. Geopolymer microspheres were prepared from red mud and granulated blast furnace slag as raw materials by alkali activation. When the red mud doping was 50%, the concentration of NaOH solution was 6 mol/L, and the additive amount was 30 mL, the prepared geopolymer microspheres possessed good morphological characteristics and a large specific surface area of 38.80 m2/g. With the loading of BiOX (X = Cl, Br, I) photocatalysts on the surface of geopolymer microspheres, 85.71% of formaldehyde gas were adsorbed within 60 min. The formaldehyde degradation rate of the geopolymer microspheres loaded with BiOI reached 87.46% within 180 min, which was 23.07% higher than that of the microspheres loaded with BiOBr, and 50.50% higher than that of the microspheres loaded with BiOCl. While ensuring the efficient degradation of formaldehyde, the BiOX (X = Cl, Br, I)-loaded geopolymer microspheres are easy to recycle and can save space. This work not only promotes the resource utilization of red mud and granulated blast furnace slag, but also provides a new idea on the formation of catalysts in the process of photocatalytic degradation of formaldehyde.

Recent Progress of Bioinspired Cell Membrane in Cancer Immunotherapy.

By modifying immune cells, immunotherapy can activate immune response to establish long-term immune memory and prevent tumor recurrence. However, their effectiveness is largely constricted by the poor immunogenicity, immune escape, and immune tolerance of the tumor. This is related to the characteristics of the tumor itself, such as genome instability and mutation. The combination of various nanocarriers with tumor immunotherapy is beneficial for overcoming the shortcomings of traditional immunotherapy. Nanocarriers coated by cell membranes can extend blood circulation time, improve ability to evade immune clearance, and enhance targeting, thus significantly enhancing the efficacy of immunotherapy and showing great potential in tumor immunotherapy. This article reviews the application research progress of different types of cell membrane-modified nanocarriers in tumor immunotherapy, immunotherapy combination therapy, and tumor vaccines, and provides prospects for future research.

Association of preoperative and recurrent serum carcinoembryonic antigen and outcome of colorectal cancer patients with metastatic relapse.

Background: Seldom have the associations of preoperative CEA (p-CEA) and recurrent CEA (r-CEA) levels as well as changes in p-CEA and r-CEA with survival in patients with stage I-III colorectal cancer (CRC) who have experienced metastatic relapse, been thoroughly examined. Methods: 241 consecutive patients with stage I-III CRC who experienced metastatic relapse at Fudan University Shanghai Cancer Center (FUSCC) between January 2008 and January 2016 were investigated. The influence of p-CEA, r-CEA and CEA alteration on the overall survival (OS) and relapse-to-death survival (RDS) was evaluated. The restricted cubic spline regression model was employed to explore the optimal cut-off value of CEA. Results: All 241 patients were categorized into four groups built on their CEA alteration patterns as follows: A, patients presenting elevated p-CEA levels but normal r-CEA levels (P-N); B, patients displaying normal levels of both p-CEA and r-CEA (N-N); C, patients exhibiting elevated levels of both p-CEA and r-CEA (P-P); D, patients with normal p-CEA levels but elevated r-CEA levels (N-P). The correlation between p-CEA and OS (P = 0.3266) and RDS (P = 0.2263) was insignificant. However, r-CEA exhibited a significant association with both OS (P = 0.0005) and RDS (P = 0.0002). Group A demonstrated the longest OS and RDS, whereas group D exhibited the poorest OS and RDS outcomes. For both OS and RDS, the CEA alteration groups served as an independent prognostic indicator. The optimal cut-off threshold for CEA was determined to be 5.1 ng/ml via the restricted cubic spline regression model. Conclusion: r-CEA has a stronger correlation with OS and RDS in individuals with stage I-III CRC who have experienced metastatic relapse.The change between p-CEA and r-CEA could further indicate post-relapse survival, thereby facilitating the assessment of mortality risk stratification in stage I-III CRC patients experiencing metastatic relapse.

The effect and mechanism of volatile oil emulsion from leaves of Clausena lansium (Lour.) Skeels on Staphylococcus aureus in vitro.

This study aimed to develop a suitable dosage form of volatile oil from wampee leaves and to explore its antibacterial mechanism in vitro. The chemical composition of the volatile oil from wampee leaves was determined by gas chromatography-mass spectrometry (GC-MS). Different microemulsion ratios were tested and their stabilities were investigated to determine the optimal ratio. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the wampee leaves volatile oil emulsion (WVOE) against Salmonella typhimurium (S. typhimurium) and Staphylococcus aureus (S. aureus) were determined using double-dilution and plate-counting methods, respectively. Morphological changes in these two bacteria were observed using scanning electron microscopy. Death, ultrastructural morphology, and biofilm formation were also assessed for S. aureus. Finally, we established an S. aureus-infected Lewis lung carcinoma (LLC) cell model to evaluate the protective effects of the volatile oil emulsion and the associated mechanisms. The volatile oil extracted from wampee leaves contained 37 compounds, of which 96.49% were aromatic hydrocarbons, terpenoids, and their oxygen-containing derivatives. The emulsion was most stable at 1:1 in the oil phase and 1:9 in the water phase. WVOE had poor antibacterial activity against S. typhimurium, but the MIC and MBC against S. aureus were 312.5 and 2,500 µg/mL, respectively. S. aureus survival rates were 84.6%, 14.5%, and 12.8% in the 1/2, 1, and 4 × MIC groups, respectively, compared with 97.2% in the control group. S. typhimurium survival was not affected by WVOE treatment. WVOE administration induced cavity formation and abnormal binary fission, and significantly inhibited biofilm formation in S. aureus cells. The WVOE notably reduced the number of S. aureus and inhibited TLR4, NLRP3, NF-κB, IL-6, IL-18, and TNF-α gene expression in S. aureus-infected LLC cells. The WVOE had a significant inhibitory effect on S. aureus and altered its cell membrane permeability. Moreover, it alleviated inflammation by inhibiting the NF-κB-NLRP3 pathway in S. aureus-infected LLC cells.

Transplantation of induced pluripotent stem cells-derived cardiomyocytes combined with modified Taohong Siwu decoction improved heart repair after myocardial infarction.

Objective: This study aimed to study whether modified Taohong Siwu decoction (MTHSWD) combined with human induced pluripotent stem cells-derived cardiomyocytes (iPS-CMs) transplantation can promote cardiac function in myocardial infarction (MI) nude mouse model and explore its possible mechanism. Methods: The MI mouse model was established by the ligation of left anterior descending coronary artery. After 4 weeks of gavage of MTHSWD combined with iPS-CMs transplantation, the changes in heart function of mice were examined by echocardiography. The histological changes were observed by Masson's trichrome staining. The survival and differentiation of transplanted cells were detected by double immunofluorescence staining of human nuclear antigen (HNA) and cardiac troponin T (cTnT). The number of c-kit-positive cells in the infarct area were evaluated by immunofluorescent staining. The levels of stromal cell-derived factor 1 (SDF-1), stem cell factor (SCF), vascular endothelial growth factor (VEGF) and basic fibroblast growth factor in infarcted myocardium tissues were detected by ELISA. Results: MTHSWD combined with iPS-CMs transplantation can improve the heart function of MI mice, reduce the infarct size and collagen deposition in infarct area. By immunofluorescence double-label detection of HNA and cTnT, it was found that MTHSWD combined with iPS-CMs transplantation can improve the survival and maturation of iPS-CMs. In addition, MTHSWD combined with iPS-CMs transplantation can activate more endogenous c-kit positive cardiac mesenchymal cells, and significantly increase the content of SDF-1, SCF and VEGF in myocardial tissues. Conclusions: The combination of MTHSWD with iPS-CMs transplantation promoted cardiac function of nude mice with MI by improving the survival and maturation of iPS-CMs in the infarct area, activating the endogenous c-kit positive cardiac mesenchymal cells, and increasing paracrine.

Causal Relationship between Immune Cells and Gynecological Cancers through Bidirectional and Multivariable Mendelian Randomization Analyses.

Background: Evidence suggests potential associations between gynecological malignancies and various immune cell chemicals and systems. However, establishing a causal relationship remains uncertain. Methods: This work employed Wald ratio for one single-nucleotide polymorphism (SNP) or the inverse-variance weighted method (IVW) for multiple SNPs to conduct bidirectional two-sample Mendelian randomization (MR) analysis by utilizing genome-wide association study (GWAS) data. We employed supplementary methods, including MR-Egger and weighted median methods, to detect and correct for the influence of horizontal pleiotropy. In addition, we also use colocalization analysis for further validation. Results: In IVW analysis, increases in relative count of circulating CD11c+ HLA-DR++ conventional dendritic cells (cDC) were associated with an elevated risk of breast cancer (OR [95% CI], 1.1295 [1.0632-1.2000], P = 8.044 × 10-5), while elevated levels of HLA-DR on plasmacytoid dendritic cells (DC) and HLA-DR on DC were protective against breast cancer. In addition, actual count of CD39+ resting Treg AC was also shown to be causally associated with the development of ovarian cancer, whereas a high relative count of CD28+ CD45RA- CD8+ T cells reduced the risk of cervical cancer. Sensitivity analysis revealed almost no evidence of bias in the current study. Multivariable MR (MVMR) analyses further confirmed a direct impact of the CD11c+ HLA-DR++ cDC immune phenotype on breast cancer. Colocalization analysis showed the lead SNP, rs780094, suggesting HLA-DR GWAS shared a common genetic mechanism with breast cancer. Conclusions: The MR study identified significant causal relationships between multiple immunophenotypes and breast cancer, aiming to provide clinicians with some reference for cancer prediction and explore further potential associations between immune phenotypes and gynecologic tumors.

Transcriptome-wide 1-methyladenosine functional profiling of messenger RNA and long non-coding RNA in bladder cancer.

Introduction: Post-transcriptional RNA modifications are crucial regulators of tumor development and progression. In many biological processes, N1-methyladenosine (m1A) plays a key role. However, little is known about the links between chemical modifications of messenger RNAs (mRNAs) and long noncoding RNAs (lncRNAs) and their function in bladder cancer (BLCA). Methods: Methylated RNA immunoprecipitation sequencing and RNA sequencing were performed to profile mRNA and lncRNA m1A methylation and expression in BLCA cells, with or without stable knockdown of the m1A methyltransferase tRNA methyltransferase 61A (TRMT61A). Results: The analysis of differentially methylated gene sites identified 16,941 peaks, 6,698 mRNAs, and 10,243 lncRNAs in the two groups. Gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses of the differentially methylated and expressed transcripts showed that m1A-regulated transcripts were mainly related to protein binding and signaling pathways in cancer. In addition, the differentially genes were identified that were also differentially m1A-modified and identified 14 mRNAs and 19 lncRNAs. Next, these mRNAs and lncRNAs were used to construct a lncRNA-microRNA-mRNA competing endogenous RNA network, which included 118 miRNAs, 15 lncRNAs, and 8 mRNAs. Finally, the m1A-modified transcripts, SCN2B and ENST00000536140, which are highly expressed in BLCA tissues, were associated with decreased overall patient survival. Discussion: This study revealed substantially different amounts and distributions of m1A in BLCA after TRMT61A knockdown and predicted cellular functions in which m1A may be involved, providing evidence that implicates m1A mRNA and lncRNA epitranscriptomic regulation in BLCA tumorigenesis and progression.

Transcriptome analysis of polyploid giant cancer cells and their progeny reveals a functional role for p21 in polyploidization and depolyploidization.

Polyploid giant cancer cells (PGCC) are frequently detected in tumors and are increasingly recognized for their roles in chromosomal instability and associated genome evolution that leads to cancer recurrence. We previously reported that therapy stress promotes polyploidy, and that acid ceramidase plays a role in depolyploidization. In this study, we used an RNA-seq approach to gain a better understanding of the underlying transcriptomic changes that occur as cancer cells progress through polyploidization and depolyploidization. Our results revealed gene signatures that are associated with disease-free and/or overall survival in several cancers and identified the cell cycle inhibitor CDKN1A/p21 as the major hub in PGCC and early progeny. Increased expression of p21 in PGCC was limited to the cytoplasm. We previously demonstrated that the sphingolipid enzyme acid ceramidase is dispensable for polyploidization upon therapy stress but plays a crucial role in depolyploidization. The current study demonstrates that treatment of cells with ceramide is not sufficient for p53-independent induction of p21 and that knockdown of acid ceramidase, which hydrolyzes ceramide, does not interfere with upregulation of p21. In contrast, blocking the expression of p21 with UC2288 prevented the induction of acid ceramidase and inhibited both the formation of PGCC from parental cells as well as the generation of progeny from PGCC. Taken together, our data suggest that p21 functions upstream of acid ceramidase and plays an important role in polyploidization and depolyploidization.

Phacogoniotomy versus phacotrabeculectomy for advanced primary angle-closure glaucoma with cataract: A randomized non-inferiority trial.

PURPOSE: To investigate the effectiveness and safety of phacogoniotomy versus phacotrabeculectomy (PVP) among patients with advanced primary angle-closure glaucoma (PACG) and cataracts. DESIGN: Multicenter, randomized controlled, non-inferiority trial. METHODS: A total of 124 patients (124 eyes) with advanced PACG and cataracts were enrolled, with 65 in the phacogoniotomy group and 59 in the phacotrabeculectomy group. Patients were followed up for 12 months with standardized evaluations. The primary outcome was the reduction in intraocular pressure (IOP) from baseline to 12 months postoperatively, of which a non-inferiority margin of 4 mmHg was evaluated. Secondary outcomes included the cumulative surgical success rate, postoperative complications, and changes in the number of glaucoma medications. RESULTS: After 12 months, phacogoniotomy demonstrated non-inferiority to phacotrabeculectomy in terms of IOP reduction, with mean IOP reductions of - 26.1 mmHg and - 25.7 mmHg (P = 0.383), respectively, from baseline values of around 40 mmHg. Both groups experienced a significant reduction in the mean number of medications used postoperatively (P < 0.001). The cumulative success rate was comparable between the groups (P = 0.890). However, phacogoniotomy had a lower rate of postoperative complications and interventions (12.3% and 4.6%) compared to phacotrabeculectomy (23.7% and 20.3% respectively). The phacogoniotomy group reported shorter surgery time (22.1 ± 6.5 vs. 38.8 ± 11.1 min; P = 0.030) and higher quality of life (EQ-5D-5 L) improvement at 12 months (7.0 ± 11.5 vs. 3.0 ± 12.9, P = 0.010) than the phacotrabeculectomy group. CONCLUSIONS: Phacogoniotomy was non-inferior to phacotrabeculectomy in terms of IOP reduction for advanced PACG and cataracts. Additionally, phacogoniotomy provided a shorter surgical time, lower postoperative complication rate, fewer postoperative interventions, and better postoperative quality of life.

Electronic Structure Regulated Nickel-Cobalt Bimetal Phosphide Nanoneedles for Efficient Overall Water Splitting.

Transition metal phosphides (TMPs) have been widely studied for water decomposition for their monocatalytic property for anodic or cathodic reactions. However, their bifunctional catalytic activity still remains a major challenge. Herein, hexagonal nickel-cobalt bimetallic phosphide nanoneedles with 1-3 µm length and 15-30 nm diameter supported on NF (NixCo2-xP NDs/NF) with adjusted electron structure have been successfully prepared. The overall alkaline water electrolyzer composed of the optimal anode (Ni0.67Co1.33P NDs/NF) and cathode (Ni1.01Co0.99P NDs/NF) provide 100 mA cm-2 at 1.62 V. Gibbs Free Energy for reaction paths proves that the active site in the hydrogen evolution reaction (HER) is Ni and the oxygen evolution reaction (OER) is Co in NixCo2-xP, respectively. In the HER process, Co-doping can result in an apparent accumulation of charge around Ni active sites in favor of promoting HER activity of Ni sites, and ΔGH* of 0.19 eV is achieved. In the OER process, the abundant electron transfer around Co-active sites results in the excellent ability to adsorb and desorb *O and *OOH intermediates and an effectively reduced ∆GRDS of 0.37 eV. This research explains the regulation of electronic structure change on the active sites of bimetallic materials and provides an effective way to design a stable and effective electrocatalytic decomposition of alkaline water.

Establishment and Characterization of an Epstein-Barr Virus-positive Cell Line from a Non-keratinizing Differentiated Primary Nasopharyngeal Carcinoma.

Nasopharyngeal carcinoma (NPC), a cancer that is etiologically associated with the Epstein-Barr virus (EBV), is endemic in Southern China and Southeast Asia. The scarcity of representative NPC cell lines owing to the frequent loss of EBV episomes following prolonged propagation and compromised authenticity of previous models underscores the critical need for new EBV-positive NPC models. Herein, we describe the establishment of a new EBV-positive NPC cell line, designated NPC268 from a primary non-keratinizing, differentiated NPC tissue. NPC268 can undergo productive lytic reactivation of EBV and is highly tumorigenic in immunodeficient mice. Whole-genome sequencing revealed close similarities with the tissue of origin, including large chromosomal rearrangements, while whole-genome bisulfite sequencing and RNA sequencing demonstrated a hypomethylated genome and enrichment in immune-related pathways, respectively. Drug screening of NPC268 together with six other NPC cell lines using 339 compounds, representing the largest high-throughput drug testing in NPC, revealed biomarkers associated with specific drug classes. NPC268 represents the first and only available EBV-positive non-keratinizing differentiated NPC model, and extensive genomic, methylomic, transcriptomic, and drug response data should facilitate research in EBV and NPC, where current models are limited. SIGNIFICANCE: NPC268 is the first and only EBV-positive cell line derived from a primary non-keratinizing, differentiated nasopharyngeal carcinoma, an understudied but important subtype in Southeast Asian countries. This model adds to the limited number of authentic EBV-positive lines globally that will facilitate mechanistic studies and drug development for NPC.

Inferring the diagnostic potential of 18F-FDG-PET/CT in post-renal transplantation from a unique case harboring multiple rare complications.

Renal transplantation is undoubtedly an effective treatment for patients with end-stage renal disease, but it is certainly not a cure. Patients require lifelong immunosuppression to maintain optimal allograft function, and post-operative risk complications such as cancer in the transplant recipient cannot be ignored. Besides, infection is a silent complication that follows transplantation. Relatedly, herein, we present a report of a 40-year-old patient who underwent renal transplantation and promptly developed a diffuse large B-cell tumor in the liver and Aspergillus infection in the trachea. In addition, an inflammatory necrotizing granuloma was also observed in the muscles. Of importance, we also described the potential of 18F-FDG-PET/CT, which was instrumental in monitoring and evaluating these relevant post-operative complications in this rare case.

Effect of Saccharomyces cerevisiae Postbiotics and Essential Oil on Growth Performance and Intestinal Health of Weanling Pigs During K88 ETEC Infection.

Enterotoxigenic Escherichia coli (ETEC) is one of the major bacterial infections, causing substantial economic losses globally in the swine industry. This study aimed to investigate the impact of low Saccharomyces cerevisiae fermentation postbiotics (SCFP), high SCFP, essential oil (EO), or their combination on the growth performance and health of weanling pigs during ETEC infection. Forty-eight male weanling pigs were randomly allocated to five groups: 1) control group (CON-basal diet, n = 16); 2) low SCFP group (LSC-basal diet + 1.25 g/kg SCFP, n = 8); 3) high SCFP group (HSC-basal diet + 2 g/kg SCFP, n = 8); 4) essential oil group (EO-basal diet + 0.4 g/kg EO, n = 8); 5) the SCFP and EO combination group (SE-basal diet + 1.25 g/kg SCFP + 0.4 g/kg EO, n = 8). On day 15 of the trial, pigs in CON were divided into positive control (PC) and negative control (NC), and all pigs, except in NC, were challenged with ETEC. Under the normal condition, dietary LSC, HSC, EO, and EO all increased average daily gain (ADG) (P < 0.05), and decreased F:G ratio (P < 0.05) accompanied by decreased malondialdehyde (MDA) and increases in catalase (CAT), total superoxide dismutase (T-SOD), total antioxidant capacity (T-AOC) indicating enhanced anti-oxidative capacity, as well as decreased IL-2, IL-8, INF-γ, indicating mitigated systemic inflammation. During ETEC infection, all treatments alleviated ETEC-induced ADG reduction, diarrhea, damages in intestinal permeability and morphology, and down-regulation of tight junctions (Claudin1, ZO-1, and Occludin), while HSC and EO exhibited additional protections. All treatments increased CAT, T-SOD, and T-AOC, and decreased MDA in serum and jejunal mucosa at similar degrees (P < 0.05). Moreover, all treatments alleviated ETEC-induced inflammation as shown by decreased IL-6, TNF-α, INF-γ, and increased IL-4 and IL-10 in serum or jejunal mucosa (P < 0.05), and enhanced the immunity by increased serum IgG and mucosal sIgA (P < 0.05). HSC and SE further reduced mucosal INF-γ and TNF-α than LSC or EO aligning with their additional protection against diarrhea during ETEC infection. Additionally, the key gut bacteria (e.g., Terrisporobacter) related to the benefits of SCFP and EO were identified. In sum, all treatments enhanced growth performance and protected against ETEC-induced intestinal damage through the regulation of redox and immune homeostasis. HSP and SE offered extra protection during disease for their additional control of inflammation. Our study provided new insight into the use of feed additives in the context of animal health states.

Weanling pigs are vulnerable to a variety of stressors and pathogen infections. Enterotoxigenic Escherichia coli (ETEC) is one of the leading causes of diarrhea and growth retardation in weanling pigs. The postbiotics, Saccharomyces cerevisiae fermentation postbiotics (SCFP), and essential oil (EO, mainly thymol, and cinnamaldehyde) were reported to exert health benefits in different sites of the intestine. However, whether SCFP and EO have dose and synergistic effects on weanling pigs, especially against ETEC infection, is incompletely understood. Our research has revealed that SCFP, EO, and their combination all enhanced the growth performance and intestinal barrier function, and reduced diarrhea of piglets, albeit to varying degrees, under both health conditions and ETEC infection. We further elucidated the disparity in the regulation of redox and immune homeostasis by SCFP, EO, and their combination contributing to their different action in distinct states. This has led to a reevaluation of the function of additives in the context of gut health and disease susceptibility.

Factors associated with human papillomavirus persistence after loop electrosurgical excision procedure in patients with cervical squamous intraepithelial lesion.

AIM: To seek the high-risk factors of human papillomavirus (HPV) persistence and residual lesion or recurrence after loop electrosurgical excision procedure (LEEP) focus on the predictive value of intraoperative human papilloma virus (IOP-HPV) testing. METHODS: Intraoperative endocervical sample was obtained with a cytobrush from the remained cervix of 292 patients immediately after LEEP. HPV Genotyping was performed using a polymerase chain reaction technique. All patients followed by HPV genotyping and cytology every 3-6 months. The IOP-HPV testing results and possible risk factors such as age, cytology grade, menopause status, margin involvement, preoperative HPV status, and cervical lesion grade were assessed in predicting persistence of HPV and residual lesion or recurrence after surgery. RESULTS: There were 61 (20.9%) patients presented persistent HPV infection. Multivariate analyses showed that IOP-HPV positive, post-menopause and preoperative HPV multiplex infection was strongly associated with HPV persistence after LEEP, IOP-HPV positive and post-menopause was also associated with residua or recurrent disease after LEEP. CONCLUSIONS: IOP-HPV positive, post-menopause, and preoperative HPV multiplex infection are independent predictors of HPV persistence in patients with cervical squamous intraepithelial lesion treated by LEEP. IOP-HPV test is a new approach that may potentially allow for early identification of patients at high risk of HPV persistence and residua or recurrent disease after LEEP, thereby possibly facilitate an attenuated follow-up schedule for negative patients those at low risk of persistent HPV infection.

Bitter taste receptors in the reproductive system: Function and therapeutic implications.

Type 2 taste receptors (TAS2Rs), traditionally known for their role in bitter taste perception, are present in diverse reproductive tissues of both sexes. This review explores our current understanding of TAS2R functions with a particular focus on reproductive health. In males, TAS2Rs are believed to play potential roles in processes such as sperm chemotaxis and male fertility. Genetic insights from mouse models and human polymorphism studies provide some evidence for their contribution to male infertility. In female reproduction, it is speculated that TAS2Rs influence the ovarian milieu, shaping the functions of granulosa and cumulus cells and their interactions with oocytes. In the uterus, TAS2Rs contribute to uterine relaxation and hold potential as therapeutic targets for preventing preterm birth. In the placenta, they are proposed to function as vigilant sentinels, responding to infection and potentially modulating mechanisms of fetal protection. In the cervix and vagina, their analogous functions to those in other extraoral tissues suggest a potential role in infection defense. In addition, TAS2Rs exhibit altered expression patterns that profoundly affect cancer cell proliferation and apoptosis in reproductive cancers. Notably, TAS2R agonists show promise in inducing apoptosis and overcoming chemoresistance in these malignancies. Despite these advances, challenges remain, including a lack of genetic and functional studies. The application of techniques such as single-cell RNA sequencing and clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated endonuclease 9 gene editing could provide deeper insights into TAS2Rs in reproduction, paving the way for novel therapeutic strategies for reproductive disorders.

A global phase 3 study of serplulimab plus chemotherapy as first-line treatment for advanced squamous non-small-cell lung cancer (ASTRUM-004).

Combining immunotherapy with chemotherapy can provide improved survival in advanced squamous non-small-cell lung cancer (NSCLC) patients without targetable gene alterations. 537 previously untreated patients with stage IIIB/IIIC or IV squamous NSCLC without targetable gene alterations were enrolled and randomized (2:1) to receive serplulimab 4.5 mg/kg or placebo, both in combination with nab-paclitaxel and carboplatin, intravenously in 3-week cycles. The primary endpoint of progression-free survival (PFS) was met at the first interim analysis. At the second interim analysis, PFS benefit was maintained in serplulimab-chemotherapy group (hazard ratio [HR] 0.53, 95% confidence interval [CI] 0.42-0.67). At the final analysis, serplulimab-chemotherapy significantly improved median OS compared to placebo-chemotherapy (HR 0.73, 95% CI 0.58-0.93; p = 0.010). Grade ≥3 serplulimab or placebo-related adverse events occurred in 126 (35.2%) and 58 (32.4%) patients, respectively. Our results demonstrate that adding serplulimab to chemotherapy significantly improves survival in advanced squamous NSCLC patients, with manageable safety.

Quality assessment of radiomics models in carotid plaque: a systematic review.

Background: Although imaging techniques provide information about the morphology and stability of carotid plaque, they are operator dependent and may miss certain subtleties. A variety of radiomics models for carotid plaque have recently been proposed for identifying vulnerable plaques and predicting cardiovascular and cerebrovascular diseases. The purpose of this review was to assess the risk of bias, reporting, and methodological quality of radiomics models for carotid atherosclerosis plaques. Methods: A systematic search was carried out to identify available literature published in PubMed, Web of Science, and the Cochrane Library up to March 2023. Studies that developed and/or validated machine learning models based on radiomics data to identify and/or predict unfavorable cerebral and cardiovascular events in carotid plaque were included. The basic information of each piece of included literature was identified, and the reporting quality, risk of bias, and radiomics methodology quality were assessed according the TRIPOD (Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis) checklist, the Prediction Model Risk of Bias Assessment Tool (PROBAST), and the radiomics quality score (RQS), respectively. Results: A total of 2,738 patients from 19 studies were included. The mean overall TRIPOD adherence rate was 66.1% (standard deviation 12.8%), with a range of 45-87%. All studies had a high overall risk of bias, with the analysis domain being the most common source of bias. The mean RQS was 9.89 (standard deviation 5.70), accounting for 27.4% of the possible maximum value of 36. The mean area under the curve for diagnostic or predictive properties of these included radiomics models was 0.876±0.09, with a range of 0.741-0.989. Conclusions: Radiomics models may have value in the assessment of carotid plaque, the overall scientific validity and reporting quality of current carotid plaque radiomics reports are still lacking, and many barriers must be overcome before these models can be applied in clinical practice.