Hemicellulose and unlocking potential for sustainable applications in biomedical, packaging, and material sciences: A narrative review.

Hemicellulose, a complex polysaccharide abundantly found in plant cell walls, has garnered significant attention for its versatile applications in various fields including biomedical, food packaging, environmental, and material sciences. This review systematically explores the composition, extraction methods, and diverse applications of hemicellulose-derived materials. Various extraction techniques such as organic acid, organic base, enzyme-assisted, and hydrothermal methods are discussed in detail, highlighting their efficacy and potential drawbacks. The applications of hemicellulose encompass biodegradable films, edible coatings, advanced hydrogels, and emulsion stabilizers, each offering unique properties suitable for different industrial needs. Current challenges in hemicellulose research include extraction efficiency, scalability of production processes, and optimization of material properties. Opportunities for future research are outlined, emphasizing the exploration of new applications and interdisciplinary approaches to harness the full potential of hemicellulose. This comprehensive review aims to provide valuable insights for researchers and industry professionals interested in utilizing hemicellulose as a sustainable and functional biomaterial.

Anticancer agent 5-fluorouracil reverses meropenem resistance in carbapenem-resistant Gram-negative pathogens.

The global increasing incidence of clinical infections caused by carbapenem-resistant Gram-negative pathogens requires urgent and effective treatment strategies. Antibiotic adjuvants represent a promising approach to enhance the efficacy of meropenem against carbapenem-resistant bacteria. This study shows that the anticancer agent 5-fluorouracil (5-FU, 50 µM) significantly reduced the minimum inhibitory concentration of meropenem against blaNDM-5 positive Escherichia coli by 32-fold through cell-based high-throughput screening. Further pharmacological studies indicated that 5-FU exhibited potentiation effects on carbapenem antibiotics against 42 Gram-negative bacteria producing either metallo-ß-lactamases (MBLs), such as NDM and IMP, or serine ß-lactamases (Ser-BLs), like KPC and OXA. These bacteria included E. coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter spp., 32 of which were obtained from human clinical samples. Mechanistic investigations revealed that 5-FU inhibited the transcription and expression of the blaNDM-5 gene. In addition, 5-FU combined with meropenem enhanced bacterial metabolism, and stimulated the production of reactive oxygen species (ROS), thereby rendering bacteria more susceptible to meropenem. In a mouse systemic infection model, 5-FU combined with meropenem reduced bacterial loads and effectively elevated the survival rate of 83.3%, compared with 16.7% with meropenem monotherapy. Collectively, these findings indicate the potential of 5-FU as a novel meropenem adjuvant to improve treatment outcomes against infections caused by carbapenem-resistant bacteria.

Vascular development analysis: a study for tertiary anti-vascular endothelial growth factor therapy after second reactivation of retinopathy of prematurity.

Purpose: To observe the vascular development results of tertiary anti-vascular endothelial growth factor (anti-VEGF) therapy following spontaneous second reactivation of retinopathy of prematurity (ROP). Methods: This retrospective study included 22 infants (42 eyes) with Type 1 or aggressive ROP (A-ROP) who received three anti-VEGF drug treatments for ROP from January 2018 to December 2022. The vascular growth, possible associated risk factors, and the retinal vascularization (DB/DF ratio) were assessed. Results: The mean follow-up was 17.6 months. After the 3rd intravitreal injection, seven eyes showed complete vascularization (Group 1), while the remaining 35 eyes demonstrated persistent avascular retina (PAR) (Group 2). In Group 2, 17 eyes maintained a stable state and were classified in the regression subgroup. The other 18 eyes developed a 3rd reactivation (reactivation subgroup) and were treated with laser photocoagulation (LPC).Birth weight (BW) was significantly lower in Group 2 than in Group 1 (p < 0.001). The decision tree analysis shows that only infants weighing more than 1,250 g (17.50%) had a chance to achieve complete retinal vascularization. The possibility of PAR was higher in patients with BW <1,250 g than ≥1,250 g (70.00% vs. 12.50%). In addition, most infants with BW ≥ 1,290 g and initial ROP disease in Zone I or posterior Zone II developed PAR. Conclusion: Tertiary IVR can successfully treat a second ROP reactivation and improve peripheral retinal vascularization. BW is the most significant factor related to complete retinal vascularization. Our decision tree model may be helpful in predicting the prognosis of anti-VEGF drugs in the event of a second ROP reactivation.

Effects of fermented jujube powder on growth performance, rumen fermentation, and antioxidant properties of simmental bulls.

Introduction: Fermented jujube powder (FJP) promotes a balance between the intestinal microflora and immune factors in animals. In this study, we aimed to investigate the effects of FJP on the production performance, nutrient digestion, rumen fermentation, and antioxidant properties of bulls. Methods: Forty Simmental bulls were randomly divided into four groups based on body weight and fed a basal diet with [5, 7.5, or 10% dry matter (DM)] or without FJP. The experimental period was 20 d for adaptation and 60 d for the feeding trial. Results: Dietary FJP supplementation did not affect DM intake (P > 0.05) but increased the average daily gain quadratically (P = 0.049) and decreased the feed conversion ratio linearly (P = 0.042). FJP quadratically enhanced DM and crude protein digestibility (P = 0.026 and P = 0.041, respectively) and linearly enhanced acid detergent fiber digestibility (P = 0.048). It also increased the total volatile fatty acid concentration quadratically (P = 0.037), acetate molar percentage, and acetate-to-propionate ratio linearly (P = 0.002 and 0.001), and reduced the ammonia nitrogen concentration linearly (P = 0.003). Additionally, xylanase and protease activities and Ruminococcus flavefaciens abundance increased linearly (P = 0.006, 0.018, and 0.009, respectively), and total bacteria, Ruminococcus albus, and Ruminobacter amylophilus abundance increased quadratically (P = 0.047, 0.011, and 0.021, respectively). FJP linearly increased serum total protein concentration and antioxidant capacity (P = 0.003 and 0.018, respectively) and decreased malonaldehyde content (P = 0.006). Discussion: FJP supplementation (7.5%) enhanced production performance, nutrient digestion, rumen fermentation, and serum antioxidant capacity in bulls. The improved nutrient digestion may be due to an increase in ruminal microorganisms and total volatile fatty acids from the FJP. High blood antioxidant levels indicate that FJP may preserve proteins, thereby boosting the production performance of bulls.

Corneal injury repair and the potential involvement of ZEB1.

The cornea, consisting of three cellular and two non-cellular layers, is the outermost part of the eyeball and frequently injured by external physical, chemical, and microbial insults. The epithelial-to-mesenchymal transition (EMT) plays a crucial role in the repair of corneal injuries. Zinc finger E-box binding homeobox 1 (ZEB1), an important transcription factor involved in EMT, is expressed in the corneal tissues. It regulates cell activities like migration, transformation, and proliferation, and thereby affects tissue inflammation, fibrosis, tumor metastasis, and necrosis by mediating various major signaling pathways, including transforming growth factor (TGF)-ß. Dysfunction of ZEB1 would impair corneal tissue repair leading to epithelial healing delay, interstitial fibrosis, neovascularization, and squamous cell metaplasia. Understanding the mechanism underlying ZEB1 regulation of corneal injury repair will help us to formulate a therapeutic approach to enhance corneal injury repair.

Heat shock protein 90 and prolyl hydroxylase 2 co-regulate hypoxia-inducible factor-1α expression in porcine small intestinal epithelial cells under heat stress.

Heat stress (HS) poses a substantial threat to animal growth and development, resulting in declining performance and economic losses. The intestinal system is susceptible to HS and undergoes intestinal hyperthermia and pathological hypoxia. Hypoxia-inducible factor-1α (HIF-1α), a key player in cellular hypoxic adaptation, is influenced by prolyl-4-hydroxylase 2 (PHD2) and heat shock protein 90 (HSP90). However, the comprehensive regulation of HIF-1α in the HS intestine remains unclear. This study aims to explore the impact of HS on pig intestinal mucosa and the regulatory mechanism of HIF-1α. Twenty-four Congjiang Xiang pigs were divided into the control and five HS-treated groups (6, 12, 24, 48, and 72 h). Ambient temperature and humidity were maintained in a thermally-neutral state (temperature-humidity index (THI) < 74) in the control group, whereas the HS group experienced moderate HS (78 < THI <84). Histological examination revealed villus exfoliation after 12 h of HS in the duodenum, jejunum, and ileum, with increasing damage as HS duration extended. The villus height to crypt depth ratio (V/C) decreased and goblet cell number increased with prolonged HS. Quantitative real-time PCR, Western blot, and immunohistochemistry analysis indicated increased expression of HIF-1α and HSP90 in the small intestine with prolonged HS, whereas PHD2 expression decreased. Further investigation in IPEC-J2 cells subjected to HS revealed that overexpressing PHD2 increased PHD2 mRNA and protein expression, while it decreases HIF-1α. Conversely, interfering with HSP90 expression substantially decreased both HSP90 and HIF-1α mRNA and protein levels. These results suggest that HS induces intestinal hypoxia with concomitant small intestinal mucosal damage. The expression of HIF-1α in HS-treated intestinal epithelial cells may be co-regulated by HSP90 and PHD2 and is possibly linked to intestinal hyperthermia and hypoxia.

KAT6A deficiency impairs cognitive functions through suppressing RSPO2/Wnt signaling in hippocampal CA3.

Intellectual disability (ID) affects ~2% of the population and ID-associated genes are enriched for epigenetic factors, including those encoding the largest family of histone lysine acetyltransferases (KAT5-KAT8). Among them is KAT6A, whose mutations cause KAT6A syndrome, with ID as a common clinical feature. However, the underlying molecular mechanism remains unknown. Here, we find that KAT6A deficiency impairs synaptic structure and plasticity in hippocampal CA3, but not in CA1 region, resulting in memory deficits in mice. We further identify a CA3-enriched gene Rspo2, encoding Wnt activator R-spondin 2, as a key transcriptional target of KAT6A. Deletion of Rspo2 in excitatory neurons impairs memory formation, and restoring RSPO2 expression in CA3 neurons rescues the deficits in Wnt signaling and learning-associated behaviors in Kat6a mutant mice. Collectively, our results demonstrate that KAT6A-RSPO2-Wnt signaling plays a critical role in regulating hippocampal CA3 synaptic plasticity and cognitive function, providing potential therapeutic targets for KAT6A syndrome and related neurodevelopmental diseases.

Schiff base functionalized dialdehyde starch for enhanced removal of Cu (II): Preparation, performances, DFT calculations.

Dialdehyde starch modified by 2-hydrazinopyridine (HYD-DAS) based on the reaction of dialdehyde starch (DAS) and 2-hydrazinopyridine was synthesized and characterized by FT-IR spectra, element analysis and SEM. HYD-DAS can efficiently adsorb Cu (II) ion to demonstrate visual color changes from yellow to dark brown in aqueous solutions. The influence on HYD-DAS to Cu (II) adsorption including pH value of solution, isotherm, kinetics, thermodynamics and possible mechanism had also been examined. Batch experiments indicate that HYD-DAS's to Cu (II) adsorption reaches equilibrium within 250 min, and its adsorption capacity and rate are 195.75 mg/g and 98.63 %, respectively. Moreover, HYD-DAS to Cu (II) adsorption remains robust and underscoring after five cycles to exhibit good selectivity and reusability. Kinetics studies suggest the absorption process follows a quasi-second-order with isotherms aligning to the Langmuir monolayer model, and thermodynamics reveals that it is a spontaneous endothermic nature of adsorption. Based on the analyses of XPS and DFT calculations, a possible mechanism for HYD-DAS to Cu (II) adsorption is that Cu (II) combined with nitrogen atoms from Schiff base and hydrazine pyridine ring in HYD-DAS.

Conditional deletion of Zeb1 in Csf1r+ cells reduces inflammatory response of the cornea to alkali burn.

ZEB1 is an essential factor in embryonic development. In adults, it is often highly expressed in malignant tumors with low expression in normal tissues. The major biological function of ZEB1 in developing embryos and progressing cancers is to transdifferentiate cells from an epithelial to mesenchymal phenotype; but what roles ZEB1 plays in normal adult tissues are largely unknown. We previously reported that the reduction of Zeb1 in monoallelic global knockout (Zeb1+/-) mice reduced corneal inflammation-associated neovascularization following alkali burn. To uncover the cellular mechanism underlying the Zeb1 regulation of corneal inflammation, we functionally deleted Zeb1 alleles in Csf1r+ myeloid cells using a conditional knockout (cKO) strategy and found that Zeb1 cKO reduced leukocytes in the cornea after alkali burn. The reduction of immune cells was due to their increased apoptotic rate and linked to a Zeb1-downregulated apoptotic pathway. We conclude that Zeb1 facilitates corneal inflammatory response by maintaining Csf1r+ cell viability.

Comparison of Radiofrequency Ablation and Craniotomy Microvascular Decompression for Treatment of Hemifacial Spasm.

BACKGROUND: Hemifacial spasm (HFS) is distinguished by sudden and involuntary spasms of the facial muscles, predominantly on one side of the face. Microvascular decompression (MVD) is an efficacious surgical technique for treating HFS; however, MVD may occasionally lead to noteworthy postoperative complications. Previously, we reported the successful utilization of an innovative awake computed tomography-guided percutaneous puncture of the stylomastoid foramen for administering radiofrequency ablation (RFA) therapy in the treatment of HFS. STUDY DESIGN: Prospective clinical research study. SETTING: Department of Anesthesiology and Pain Medical Center, Ningbo, China. OBJECTIVES: The aim of this study was to compare and contrast the clinical outcomes and adverse reactions associated with attempts to use RFA and MVD to manage primary HFS. METHODS: Three hundred patients received either RFA or MVD treatment (Group R and Group M). We tracked and recorded each patient's cure rate, remission rate, intraoperative and postoperative complications, short-term and long-term therapeutic outcomes, hospitalization duration, hospitalization expenses, and operation time. RESULTS: One hundred and fifty-eight patients were placed in the R group, and 142 patients were sorted into the M group. In the R group, 87.34% of patients showed improvement, 9.49% experienced relief, and 3.16% experienced treatment failure. Similarly, in the M group, 85.92% of patients showed improvement, 10.56% experienced relief, and 3.52% experienced treatment failure. The difference in therapeutic efficacy between the 2 groups was not significant. However, the M group had significantly lower recurrence rates at 3 months, 6 months, and one year post-operation than the R group did. Notably, the M group also experienced a higher rate of postoperative complications. Among the complications reported in the M group were 25 cases of dizziness or headache (17.6%) following the operation, 22 cases of hearing damage, including one case of complete hearing loss on the side involved, and 28 cases of peripheral nerve injury with abnormal skin sensation. Postoperative facial paralysis occurred in 15 patients, including 10 cases of moderate to severe facial paralysis that were relieved to grade II after one year. In comparison, the R group had 40 cases of grade II and 53 cases of grade III, and no cases of more severe facial paralysis were found. There were also 13 cases of peripheral nerve injury, such as local skin numbness and tenderness. Importantly, there were no cases of facial hematoma, intracranial hemorrhage, infection, or any other complications in either group, and no fatalities occurred during the study period. LIMITATIONS: The limitations of this study are the exclusion of transient postoperative complications, the lack of in-person follow-up with patients, and the potential underestimation of certain complications. CONCLUSION: The short-term outcome was found to be comparable between the 2 treatment modalities. Notably, RFA demonstrates both safety and efficacy as a method for managing primary HFS; however, the procedure may lead to mild facial paralysis. In situations during which surgery is contraindicated, especially among elderly or high-risk surgical patients, percutaneous facial nerve RFA at the stylomastoid foramen may be considered as an alternative therapeutic approach.

Hypoxia-inducible factor 1α inhibits heat stress-induced pig intestinal epithelial cell apoptosis through eif2α/ATF4/CHOP signaling.

Unstoppable global warming and increased frequency of extreme heat leads to human and animals easier to suffer from heat stress (HS), with gastrointestinal abnormalities as one of the initial clinical symptoms. HS induces intestinal mucosal damage owing to intestinal hypoxia and hyperthermia. Hypoxia-inducible factor 1α (HIF-1α) activates numerous genes to mediate cell hypoxic responses; however, its role in HS-treated intestinal mucosa is unknown. This work aimed to explore HIF-1α function and regulatory mechanisms in HS-treated pig intestines. We assigned 10 pigs to control and moderate HS groups. Physical signs, stress, and antioxidant levels were detected, and the intestines were harvested after 72 h of HS treatment to study histological changes and HIF-1α, heat shock protein 90 (HSP90), and prolyl-4-hydroxylase 2 (PHD-2) expression. In addition, porcine intestinal columnar epithelial cells (IPEC-J2) underwent HS treatment (42 °C, 5 % O2) to further explore the functions and regulatory mechanism of HIF-1α. The results of histological examination revealed HS caused intestinal villi damage and increased apoptotic epithelial cell; the expression of HIF-1α and HSP90 increased while PHD-2 showed and opposite trend. Transcriptome sequencing analysis revealed that HS activated HIF-1 signaling. To further explore the role of HIF-1α on HS induced IPEC-J2 apoptosis, the HIF-1α was interfered and overexpression respectively, and the result confirmed that HIF-1α could inhibited cell apoptosis under HS. Furthermore, HS-induced apoptosis depends on eukaryotic initiation factor 2 alpha (eif2α)/activating transcription factor 4 (ATF4)/CCAAT-enhancer-binding protein homologous protein (CHOP) pathway, and HIF-1α can inhibit this pathway to alleviate IPEC-J2 cell apoptosis. In conclusion, this study suggests that HS can promote intestinal epithelial cell apoptosis and cause pig intestinal mucosal barrier damage; the HIF-1α can alleviate cell apoptosis by inhibiting eif2α/ATF4/CHOP signaling. These results indicate that HIF-1α plays a protective role in HS, and offers a potential target for HS prevention and mitigation.

Echo-Level SAR Imaging Simulation of Wakes Excited by a Submerged Body.

The paper introduces a numerical simulation method for Synthetic Aperture Radar (SAR) imaging of submerged body wakes by integrating hydrodynamics, electromagnetic scattering, and SAR imaging simulation. This work is helpful for better understanding SAR images of submerged body wakes. Among these, the hydrodynamic model consists of two sets of ocean dynamics closely related to SAR imaging, namely the wake of the submerged body and wind waves. For the wake, we simulated it using computational fluid dynamics (CFD) numerical methods. Furthermore, we compared and computed the electromagnetic scattering characteristics of wakes under various navigation parameters and sea surface conditions. Following that, based on the operational principles and imaging theory of synthetic aperture radar (SAR), we established the SAR raw echo signal of the wake. Employing a Range-Doppler (RD) algorithm, we generated simulated SAR images of the wake. The results indicate that utilizing Computational Fluid Dynamics (CFD) numerical methods enables the simulation of wake characteristics generated by the motion of a submerged body with different velocities. The backscattering features of wakes are closely associated with the relative orientation between the wake and the radar line of sight. Under specific wind speeds, the wake gets masked within the sea surface background, resulting in less discernible characteristics of the wake in SAR images. This suggests that at lower speeds of submerged body or under specific wind conditions, the detectability of the wake in SAR images significantly diminishes.

Short chain fatty acids inhibit corneal inflammatory responses to TLR ligands via the ocular G-protein coupled receptor 43.

PURPOSE: Short chain fatty acids (SCFAs) produced by gut microbiota are known to play primary roles in gut homeostasis by immunomodulation partially through G-protein coupled receptors (GPR) 43. Using mouse models of TLR ligand induced keratitis, we investigated whether SCFAs and GPR43 play any regulatory roles in the pathogenesis of inflammatory responses in the eye. METHODS: Both human and mouse eyes were labeled with a specific antibody for GPR43 and imaged by a laser scanning confocal microscope. Corneal cups from naïve C57BL/6J (B6) and GPR43 knockout (KO) mice were stimulated with TLR ligands in the presence or absence of sodium butyrate overnight and then processed for RT-PCR assay for expression of GPR43 and cytokines. Keratitis was induced by Poly I:C in wild type (WT) B6, GPR43KO and chimeric mice and the disease severity was evaluated by the corneal fluorescein staining test, and infiltrating cell staining and calculating in corneal whole mount. RESULTS: GPR43 is expressed in both human and mouse eyes and the expression is bidirectionally regulated by TLR ligands and butyrate. Butyrate significantly inhibited inflammation caused by several TLR ligands such as Poly I:C, Flagellin, and CpG-ODN (TLR-3, 5 and 9 agonists, respectively) in WT, but not GPR43KO, mice. Butyrate inhibition of TLR-induced keratitis is mediated by the GPR43 expressed in tissue but not hematopoietic, cells. CONCLUSIONS: This is the first report to demonstrate of the protective effect of SCFAs on microbial keratitis, and the dynamic expression and anti-inflammatory function of GPR43 in the eye. SCFAs can modulate inflammation and immunity in the eye through GPR43.

Attenuation of pro-tumorigenic senescent secretory phenotype by StN, a novel derivative of stevioside, potentiates its inhibitory activity on hepatocellular carcinoma.

Ent-13-Hydroxy-15-kaurene-19-acid N-Methylpiperazine Ethyl Ester (StN) is a novel derivative of the natural diterpene stevioside isolated from Stevia rebaudiana (Bertoni). In this study, we examined the effects of StN against hepatocellular carcinoma (HCC) in vitro and in vivo as well as its anticancer mechanisms by inhibiting proliferation and regulating the senescence-associated secretory phenotype (SASP). We showed that StN significantly inhibited HCC cell proliferation by inducing cellular senescence, as observed by increased senescence-associated ß-galactosidase activity and cell cycle arrest. Mechanistically, StN impaired lysosomal stability and triggered the release of cathepsin B from the lysosomes into the nucleus where it promoted DNA damage. Cathepsin B-mediated DNA damage contributed to cellular senescence triggered by StN. Meanwhile, StN transcriptionally suppressed multiple pro-inflammatory SASP components, including IL-6, IL-1α, IL-1ß, and IL-8, resulting in the reduction of pro-tumorigenic impact of SASP. Further study revealed that StN inactivated NF-κB and PI3K/Akt signaling, which significantly accounted for its inhibition on the SASP factors. In HCC xenograft mice, administration of StN significantly suppressed tumor growth, while no significant toxicity was detected. This study demonstrates a novel mechanism that suppressing the SASP by StN in senescent cells potentiates its anticancer efficacy, thus defining a potential compound for cancer treatment.

Analysis of Onboard Verification Flight Test for the Salinity Satellite Scatterometer.

The upcoming Salinity Satellite, scheduled for launch in 2024, will feature the world's first phased array radar scatterometer. To validate its capability in measuring ocean surface backscatter coefficients, this paper conducts an in-depth analysis of the onboard verification flight test for the Salinity Satellite scatterometer. This paper provides a detailed introduction to the system design of the Salinity Satellite scatterometer, which utilizes phased array radar technology and digital beamforming techniques to achieve accurate measurements of sea surface scattering characteristics. The paper elaborates on the derivation of backscatter coefficients, system calibration, and phase amplitude correction for the phased array scatterometer. Furthermore, it describes the process of the onboard calibration flight test. By analyzing internal noise signals, onboard calibration signals, and external noise signals, the stability and reliability of the scatterometer system are validated. The experiment covers both land and ocean observations, with a particular focus on complex sea surface conditions in nearshore areas. Through the precise analysis of backscatter coefficients, the paper successfully distinguishes the different backscatter coefficient characteristics between ocean and land. The research results effectively demonstrate the feasibility of the Salinity Satellite scatterometer for measuring backscatter coefficients in a phased array configuration, as well as its outstanding performance in complex marine environments.

Mouse Corneal Epithelial and Stromal Cell Isolation and Culture.

Corneal epithelium and stroma are the major cellular structures for ocular protection and vision accuracy; they play important roles in corneal wound healing and inflammation under pathological conditions. Unlike human, murine corneal and stromal fibroblast cells are difficult to isolate for cell culture. In our laboratory, we successfully used an ex vivo culture procedure and an enzymatic procedure to isolate, purify, and culture mouse corneal epithelial and stromal fibroblast cells. Key features • Primary cell culture models of a disease are critical for cellular and molecular mechanism studies. • Corneal tissues with the limbus contain stem cells to generate both epithelial and stromal cells. • An ex vivo corneal culture provides a constant generation of primary corneal cells for multiple passages. • The isolated cells are validated by the corneal epithelial cell markers Krt12 and Cdh1 and the stromal fibroblast marker Vim.

Identification of molecular pattern and prognostic risk model based on ligand-receptor pairs in liver cancer.

Introduction: The tumor microenvironment of hepatocellular carcinoma is composed of multiple cells, and the interactive communication between cells drives tumor progression and characterizes the tumor. Communication between cells is mainly achieved through signal transduction between receptor ligands, and the rise of single-cell technology has made it possible to analyze the communication network between cells. Methods: We applied a train of bioinformatic techniques and in vitro experiments. We analyzed the composition of the microenvironment of liver cancer by combining single-cell sequencing data and transcriptome sequencing data from liver cancer to construct molecular typing and risk models for LRs. Then, we analyzed association of it with prognosis, mutation, KEGG, tumor microenvironment (TME), immune infiltration, tumor mutational burden (TMB) and drug sensitivity in liver cancer. qPCR and was used to identify SLC1A5 expression in LIHC cell lines and CCK8, transwell and cell colony formation were performed to validate the function of SLC1A5. Meanwhile, we also performed polarization of macrophages. Results: In this experiment, we found that liver cancer tissues are rich in immune and mesenchymal cells, and there is extensive signaling between individual cells, so we constructed molecular typing and risk models for LRs. Combining clinical data revealed significant differences in clinical characteristics, prognosis and mutated genes between the molecular typing of receptor-ligand pairs, as well as in sensitivity to drugs; similarly, there were significant prognostic differences between the risk models. There were also notable differences in activated signaling pathways, infiltrating immune cells and immune subtypes. Subsequently, we used siRNA to knock down SLC1A5 in hepatocellular carcinoma cells and found that cell proliferation, migration and invasion were diminished. Conclusions: In conclusion, our LRs model may become a marker to guide clinical treatment and prognosis.

Revalidation of the ATTRACTION-4 study in a real-world setting: a multicenter, retrospective propensity score matching study in China.

Background: Immune-checkpoint inhibitors (ICIs) combined with chemotherapy have been successfully used in clinical trials to treat advanced gastric cancer. However, the efficacy and safety of first-line immunotherapy combined with chemotherapy in Chinese patients are unknown. Methods: This multicenter retrospective study included patients with human epidermal growth factor receptor-2 (HER-2) negative advanced gastric cancer treated with first-line chemotherapy or chemotherapy with an ICI between January 2019 and December 2022. Propensity score matching was used to compare progression-free survival (PFS), overall survival, objective response rates, and adverse reactions between cohorts. Results: After propensity score matching, 138 patients, who had balanced baseline characteristics, were included in the chemotherapy and combination treatment groups. The median follow-up duration was 16.90 months, and the median PFS was 8.53 months (95% confidence interval [CI] 7.77-9.28) in the combination treatment group and 5.97 months (95% CI 4.56-7.37) in the chemotherapy group. The median survival duration was 17.05 months (95% CI 14.18-19.92) in the combination treatment group and 16.46 months (95% CI 12.99-19.93) in the chemotherapy group. The PFS subgroup analysis revealed that age ≥65 years, women, Eastern Cooperative Oncology Group performance status of 1, non-signet ring cell carcinoma, esophagogastric junction, liver metastasis, peritoneal metastasis, no massive ascites, only one metastatic organ, and combined platinum-based chemotherapy correlated with treatment benefit. The incidences of adverse events above grade 3 were comparable between groups. Conclusions: Our study confirmed the ATTRACTION-4 trial results. Compared with chemotherapy, first-line ICIs combined with chemotherapy prolonged PFS but did not improve overall survival in patients with HER-2-negative advanced gastric cancer.

Metabolic transcriptomics dictate responses of cone photoreceptors to retinitis pigmentosa.

Most mutations in retinitis pigmentosa (RP) arise in rod photoreceptors, but cone photoreceptors, responsible for high-resolution daylight and color vision, are subsequently affected, causing the most debilitating features of the disease. We used mass spectroscopy to follow 13C metabolites delivered to the outer retina and single-cell RNA sequencing to assess photoreceptor transcriptomes. The S cone metabolic transcriptome suggests engagement of the TCA cycle and ongoing response to ROS characteristic of oxidative phosphorylation, which we link to their histone modification transcriptome. Tumor necrosis factor (TNF) and its downstream effector RIP3, which drive ROS generation via mitochondrial dysfunction, are induced and activated as S cones undergo early apoptosis in RP. The long/medium-wavelength (L/M) cone transcriptome shows enhanced glycolytic capacity, which maintains their function as RP progresses. Then, as extracellular glucose eventually diminishes, L/M cones are sustained in long-term dormancy by lactate metabolism.

Development and validation of a contrast-enhanced CT-based radiomics nomogram for preoperative diagnosis in neuroendocrine carcinoma of digestive system.

Objectives: To develop and validate a contrast-enhanced CT-based radiomics nomogram for the diagnosis of neuroendocrine carcinoma of the digestive system. Methods: The clinical data and contrast-enhanced CT images of 60 patients with pathologically confirmed neuroendocrine carcinoma of the digestive system and 60 patients with non-neuroendocrine carcinoma of the digestive system were retrospectively collected from August 2015 to December 2021 at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, and randomly divided into a training cohort (n=84) and a validation cohort (n=36). Clinical characteristics were analyzed by logistic regression and a clinical diagnosis model was developed. Radiomics signature were established by extracting radiomic features from contrast-enhanced CT images. Based on the radiomic signature and clinical characteristics, radiomic nomogram was developed. ROC curves and Delong's test were used to evaluate the diagnostic efficacy of the three models, calibration curves and application decision curves were used to analyze the accuracy and clinical application value of nomogram. Results: Logistic regression results showed that TNM stage (stage IV) (OR 6.8, 95% CI 1.320-43.164, p=0. 028) was an independent factor affecting the diagnosis for NECs of the digestive system, and a clinical model was constructed based on TNM stage (stage IV). The AUCs of the clinical model, radiomics signature, and radiomics nomogram for the diagnosis of NECs of the digestive system in the training, validation cohorts and pooled patients were 0.643, 0.893, 0.913; 0.722, 0.867, 0.932 and 0.667, 0.887, 0.917 respectively. The AUCs of radiomics signature and radiomics nomogram were higher than clinical model, with statistically significant difference (Z=4.46, 6.85, both p < 0.001); the AUC difference between radiomics signature and radiomics nomogram was not statistically significant (Z=1.63, p = 0.104). The results of the calibration curve showed favorable agreement between the predicted values of the nomogram and the pathological results, and the decision curve analysis indicated that the nomogram had favorable application in clinical practice. Conclusions: The nomogram constructed based on contrast-enhanced CT radiomics and clinical characteristics was able to effectively diagnose neuroendocrine carcinoma of the digestive system.